Basel, Switzerland
Basel, Switzerland

The University of Basel is located in Basel, Switzerland, and is considered to be one of the leading universities in the country. In 2012, QS World University Rankings ranked the university 121st overall in the world, while two years before it was ranked 96–98th worldwide according to the Russian based Global University Ranking. In 2012, the ARWU ranked the university as the 85th best worldwide. Wikipedia.

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University of Basel and PIQUR Therapeutics | Date: 2015-04-20

The invention relates to a method of manufacturing triazine, pyrimidine and pyridine derivatives of formula (I), wherein U, V, W and Z are nitrogen or carbon atoms, whereby at least one of U, V and W is nitrogen, and the other substituents are defined as in the specification, by condensing a corresponding halo-triazine, pyrimidine or pyridine in a type of Suzuki coupling with a pyridyl- or pyrimidinyl-borane, wherein the amino function is protected as a formamidine. The invention further relates to suitable intermediates and methods of manufacturing of such intermediates. Furthermore the invention relates to pure 5-(4,6-dimorpholino-1,3,5-triazin-2-yl)-4-(trifluoromethyl)pyridin-2-amine in solid form.

Takeoka A.,University of Basel | Takeoka A.,Friedrich Miescher Institute for Biomedical Research | Vollenweider I.,Ecole Polytechnique Federale de Lausanne | Courtine G.,Ecole Polytechnique Federale de Lausanne | And 2 more authors.
Cell | Year: 2014

Spinal cord injuries alter motor function by disconnecting neural circuits above and below the lesion, rendering sensory inputs a primary source of direct external drive to neuronal networks caudal to the injury. Here, we studied mice lacking functional muscle spindle feedback to determine the role of this sensory channel in gait control and locomotor recovery after spinal cord injury. High-resolution kinematic analysis of intact mutant mice revealed proficient execution in basic locomotor tasks but poor performance in a precision task. After injury, wild-type mice spontaneously recovered basic locomotor function, whereas mice with deficient muscle spindle feedback failed to regain control over the hindlimb on the lesioned side. Virus-mediated tracing demonstrated that mutant mice exhibit defective rearrangements of descending circuits projecting to deprived spinal segments during recovery. Our findings reveal an essential role for muscle spindle feedback in directing basic locomotor recovery and facilitating circuit reorganization after spinal cord injury. © 2014 Elsevier Inc. All rights reserved.

Pivetta C.,University of Basel | Pivetta C.,Friedrich Miescher Institute for Biomedical Research | Esposito M.S.,University of Basel | Esposito M.S.,Friedrich Miescher Institute for Biomedical Research | And 4 more authors.
Cell | Year: 2014

Accurate motor-task execution relies on continuous comparison of planned and performed actions. Motor-output pathways establish internal circuit collaterals for this purpose. Here we focus on motor collateral organization between spinal cord and upstream neurons in the brainstem. We used a newly developed mouse genetic tool intersectionally with viruses to uncover the connectivity rules of these ascending pathways by capturing the transient expression of neuronal subpopulation determinants. We reveal a widespread and diverse network of spinal dual-axon neurons, with coincident input to forelimb motor neurons and the lateral reticular nucleus (LRN) in the brainstem. Spinal information to the LRN is not segregated by motor pool or neurotransmitter identity. Instead, it is organized according to the developmental domain origin of the progenitor cells. Thus, excerpts of most spinal information destined for action are relayed to supraspinal centers through exquisitely organized ascending connectivity modules, enabling precise communication between command and execution centers of movement. © 2014 Elsevier Inc.

Ruegger S.,Friedrich Miescher Institute for Biomedical Research | Ruegger S.,University of Basel | Grosshans H.,Friedrich Miescher Institute for Biomedical Research
Trends in Biochemical Sciences | Year: 2012

MicroRNAs (miRNAs) are short (∼22 nucleotide) RNAs that are important for the regulation of numerous biological processes. Accordingly, the expression of miRNAs is itself tightly controlled by mechanisms acting at the level of transcription as well as processing of miRNA precursors. Recently, active degradation of mature miRNAs has been identified as another mechanism that is important for miRNA homeostasis. Here we review the molecular factors and cellular conditions that promote miRNA turnover. We also discuss what is known about the physiological relevance of miRNA decay. © 2012 Elsevier Ltd.

Bethune J.,Friedrich Miescher Institute for Biomedical Research | Artus-Revel C.G.,Friedrich Miescher Institute for Biomedical Research | Filipowicz W.,Friedrich Miescher Institute for Biomedical Research | Filipowicz W.,University of Basel
EMBO Reports | Year: 2012

MicroRNAs (miRNAs) regulate most cellular functions, acting by posttranscriptionally repressing numerous eukaryotic mRNAs. They lead to translational repression, deadenylation and degradation of their target mRNAs. Yet, the relative contributions of these effects are controversial and little is known about the sequence of events occurring during the miRNA-induced response. Using stable human cell lines expressing inducible reporters, we found that translational repression is the dominant effect of miRNAs on newly synthesized targets. This step is followed by mRNA deadenylation and decay, which is the dominant effect at steady state. Our findings have important implications for understanding the mechanism of silencing and reconcile seemingly contradictory data. © 2012 European Molecular Biology Organization.

Avalos J.,University of Seville | Estrada A.F.,University of Basel
Fungal Genetics and Biology | Year: 2010

The genus Fusarium stands out as research model for pathogenesis and secondary metabolism. Light stimulates the production of some Fusarium metabolites, such as the carotenoids, and in many species it influences the production of asexual spores and sexual fruiting bodies. As found in other fungi with well-known photoresponses, the Fusarium genomes contain several genes for photoreceptors, among them a set of White Collar (WC) proteins, a cryptochrome, a photolyase, a phytochrome and two presumably photoactive opsins. The mutation of the opsin genes produced no apparent phenotypic alterations, but the loss of the only WC-1 orthologous protein eliminated the photoinduced expression of the photolyase and opsin genes. In contrast to other carotenogenic species, lack of the WC photoreceptor did not impede the light-induced accumulation of carotenoids, but produced alterations in conidiation, animal pathogenicity and nitrogen-regulated secondary metabolism. The regulation and functional role of other Fusarium photoreceptors is currently under investigation. © 2010 Elsevier Inc.

Rauscher T.,University of Hertfordshire | Rauscher T.,Hungarian Academy of Sciences | Rauscher T.,University of Basel
Physical Review Letters | Year: 2013

The Sm146/Sm144 ratio in the early solar system has been constrained by Nd/Sm isotope ratios in meteoritic material. Predictions of Sm146 and Sm144 production in the γ process in massive stars are at odds with these constraints, and this is partly due to deficiencies in the prediction of the reaction rates involved. The production ratio depends almost exclusively on the (γ,n)/(γ,α) branching at Gd148. A measurement of Sm144(α,γ)Gd148 at low energy had discovered considerable discrepancies between cross-section predictions and the data. Although this reaction cross section mainly depends on the optical α+nucleus potential, no global optical potential has yet been found that can consistently describe the results of this and similar α-induced reactions at the low energies encountered in astrophysical environments. The untypically large deviation in Sm144(α,γ) and the unusual energy dependence can be explained, however, by low-energy Coulomb excitation, which is competing with compound nucleus formation at very low energies. Considering this additional reaction channel, the cross sections can be described with the usual optical potential variations, compatible with findings for (n, α) reactions in this mass range. Low-energy (α, γ) and (α, n) data on other nuclei can also be consistently explained in this way. Since Coulomb excitation does not affect α emission, the Gd148(γ,α) rate is much higher than previously assumed. This leads to very small Sm146/Sm144 stellar production ratios, in even more pronounced conflict with the meteorite data. © 2013 American Physical Society.

Esposito M.S.,University of Basel | Esposito M.S.,Friedrich Miescher Institute for Biomedical Research | Capelli P.,University of Basel | Capelli P.,Friedrich Miescher Institute for Biomedical Research | And 2 more authors.
Nature | Year: 2014

Translating the behavioural output of the nervous system into movement involves interaction between brain and spinal cord. The brainstem provides an essential bridge between the two structures, but circuit-level organization and function of this intermediary system remain poorly understood. Here we use intersectional virus tracing and genetic strategies in mice to reveal a selective synaptic connectivity matrix between brainstem substructures and functionally distinct spinal motor neurons that regulate limb movement. The brainstem nucleus medullary reticular formation ventral part (MdV) stands out as specifically targeting subpopulations of forelimb-innervating motor neurons. Its glutamatergic premotor neurons receive synaptic input from key upper motor centres and are recruited during motor tasks. Selective neuronal ablation or silencing experiments reveal that MdV is critically important specifically for skilled motor behaviour, including accelerating rotarod and single-food-pellet reaching tasks. Our results indicate that distinct premotor brainstem nuclei access spinal subcircuits to mediate task-specific aspects of motor programs. © 2014 Macmillan Publishers Limited. All rights reserved.

Dion V.,Friedrich Miescher Institute for Biomedical Research | Kalck V.,Friedrich Miescher Institute for Biomedical Research | Horigome C.,Friedrich Miescher Institute for Biomedical Research | Towbin B.D.,Friedrich Miescher Institute for Biomedical Research | And 3 more authors.
Nature Cell Biology | Year: 2012

Chromatin mobility is thought to facilitate homology search during homologous recombination and to shift damage either towards or away from specialized repair compartments. However, unconstrained mobility of double-strand breaks could also promote deleterious chromosomal translocations. Here we use live time-lapse fluorescence microscopy to track the mobility of damaged DNA in budding yeast. We found that a Rad52-YFP focus formed at an irreparable double-strand break moves in a larger subnuclear volume than the undamaged locus. In contrast, Rad52-YFP bound at damage arising from a protein-DNA adduct shows no increase in movement. Mutant analysis shows that enhanced double-strand-break mobility requires Rad51, the ATPase activity of Rad54, the ATR homologue Mec1 and the DNA-damage-response mediator Rad9. Consistent with a role for movement in the homology-search step of homologous recombination, we show that recombination intermediates take longer to form in cells lacking Rad9. © 2012 Macmillan Publishers Limited. All rights reserved.

Lienert F.,Friedrich Miescher Institute for Biomedical Research | Lienert F.,University of Basel | Wirbelauer C.,Friedrich Miescher Institute for Biomedical Research | Som I.,U.S. National Institutes of Health | And 5 more authors.
Nature Genetics | Year: 2011

Cytosine methylation is a repressive, epigenetically propagated DNA modification. Although patterns of DNA methylation seem tightly regulated in mammals, it is unclear how these are specified and to what extent this process entails genetic or epigenetic regulation. To dissect the role of the underlying DNA sequence, we sequentially inserted over 50 different DNA elements into the same genomic locus in mouse stem cells. Promoter sequences of approximately 1,000 bp autonomously recapitulated correct DNA methylation in pluripotent cells. Moreover, they supported proper de novo methylation during differentiation. Truncation analysis revealed that this regulatory potential is contained within small methylation-determining regions (MDRs). MDRs can mediate both hypomethylation and de novo methylation in cis, and their activity depends on developmental state, motifs for DNA-binding factors and a critical CpG density. These results demonstrate that proximal sequence elements are both necessary and sufficient for regulating DNA methylation and reveal basic constraints of this regulation. © 2011 Nature America, Inc. All rights reserved.

Dion V.,Friedrich Miescher Institute for Biomedical Research | Gasser S.M.,Friedrich Miescher Institute for Biomedical Research | Gasser S.M.,University of Basel
Cell | Year: 2013

Mechanistic analyses based on improved imaging techniques have begun to explore the biological implications of chromatin movement within the nucleus. Studies in both prokaryotes and eukaryotes have shed light on what regulates the mobility of DNA over long distances. Interestingly, in eukaryotes, genomic loci increase their movement in response to double-strand break induction. Break mobility, in turn, correlates with the efficiency of repair by homologous recombination. We review here the source and regulation of DNA mobility and discuss how it can both contribute to and jeopardize genome stability. © 2013 Elsevier Inc.

Ecsedi M.,Friedrich Miescher Institute for Biomedical Research | Ecsedi M.,University of Basel | Rausch M.,Friedrich Miescher Institute for Biomedical Research | Rausch M.,University of Basel | Grosshans H.,Friedrich Miescher Institute for Biomedical Research
Developmental Cell | Year: 2015

The let-7 microRNA (miRNA) regulates stemness in animals ranging from worms to humans. However, the cause of the dramatic vulval rupturing phenotype of let-7 mutant C.elegans has remained unknown. Consistent with the notion that miRNAs function by coordinately tuning the expression of many targets, bursting may result from joint dysregulation of several targets, possibly in the epidermis. Alternatively, overexpression of LET-60/RAS, a key vulva development gene and a phylogenetically conserved target of let-7, may be responsible. Here, we show that let-7 functions in the vulval-uterine system to ensure vulval integrity but that regulation of most targets of let-7, including LET-60/RAS, is dispensable. Using CRISPR-Cas9 to edit endogenous let-7 target sites, we found that regulation of LIN-41/TRIM71 alone is necessary and sufficient to prevent vulval rupturing. Hence, let-7 does not function to reduce gene expression noise broadly, but to direct vulval development through extensive regulation of a single, defined target. © 2015 Elsevier Inc.

Schubeler D.,Friedrich Miescher Institute for Biomedical Research | Schubeler D.,University of Basel
Nature | Year: 2015

Cytosine methylation is a DNA modification generally associated with transcriptional silencing. Factors that regulate methylation have been linked to human disease, yet how they contribute to malignances remains largely unknown. Genomic maps of DNA methylation have revealed unexpected dynamics at gene regulatory regions, including active demethylation by TET proteins at binding sites for transcription factors. These observations indicate that the underlying DNA sequence largely accounts for local patterns of methylation. As a result, this mark is highly informative when studying gene regulation in normal and diseased cells, and it can potentially function as a biomarker. Although these findings challenge the view that methylation is generally instructive for gene silencing, several open questions remain, including how methylation is targeted and recognized and in what context it affects genome readout. © 2015 Macmillan Publishers Limited.

Meier-Abt F.,Friedrich Miescher Institute for Biomedical Research | Meier-Abt F.,University of Basel | Bentires-Alj M.,Friedrich Miescher Institute for Biomedical Research
Trends in Molecular Medicine | Year: 2014

Pregnancy at an early age has a strong protective effect against breast cancer in humans and rodents. Postulated mechanisms underlying this phenomenon include alterations in the relative dynamics of hormone and growth factor-initiated cell fate-determining signaling pathways within the hierarchically organized mammary gland epithelium. Recent studies in epithelial cell subpopulations isolated from mouse and human mammary glands have shown that early pregnancy decreases the proportion of hormone receptor-positive cells and causes pronounced changes in gene expression as well as decreased proliferation in stem/progenitor cells. The changes include downregulation of Wnt and transforming growth factor β (TGFβ) signaling. These new findings highlight the importance of cell-cell interactions within the mammary gland epithelium in modulating cancer risk and provide potential targets for breast cancer prevention strategies. © 2013 Elsevier Ltd.

Seeber A.,Friedrich Miescher Institute for Biomedical Research | Seeber A.,University of Basel | Dion V.,Friedrich Miescher Institute for Biomedical Research | Gasser S.M.,Friedrich Miescher Institute for Biomedical Research | Gasser S.M.,University of Basel
Genes and Development | Year: 2013

Double-strand break repair by recombination requires a homology search. In yeast, induced breaks move significantly more than undamaged loci. To examine whether DNA damage provokes an increase in chromatin mobility generally, we tracked undamaged loci under DNA-damaging conditions. We found that the yeast checkpoint factors Mec1, Rad9, and Rad53 are required for genome-wide increases in chromatin mobility, but not the repair protein Rad51. Mec1 activation by targeted Ddc1/Ddc2 enhances chromatin mobility even in the absence of damage. Finally, the INO80 chromatin remodeler is shown to act downstream from Mec1 to increase chromatin mobility, highlighting an additional damage-related role of this nucleosome remodeling complex. © 2013, Published by Cold Spring Harbor Laboratory Press.

Gerhold C.B.,Friedrich Miescher Institute for Biomedical Research | Gasser S.M.,Friedrich Miescher Institute for Biomedical Research | Gasser S.M.,University of Basel
Trends in Cell Biology | Year: 2014

Virtually all DNA-dependent processes require selective and controlled access to the DNA sequence. Governing this access are sophisticated molecular machines, nucleosome remodelers, which regulate the composition and structure of chromatin, allowing conversion from open to closed states. In most cases these multisubunit remodelers operate in concert to organize chromatin structure by depositing, moving, evicting, or selectively altering nucleosomes in an ATP-dependent manner. Despite sharing a conserved domain architecture, chromatin remodelers differ significantly in how they bind to their nucleosomal substrates. Recent structural studies link specific interactions between nucleosomes and remodelers to the diverse tasks they carry out. We review here insights into the modular organization of the INO80 family of nucleosome remodelers. Understanding their structural diversity will help to shed light on how these related ATPases modify their nucleosomal substrates. © 2014 Elsevier Ltd.

Baubec T.,Friedrich Miescher Institute for Biomedical Research | Schubeler D.,Friedrich Miescher Institute for Biomedical Research | Schubeler D.,University of Basel
Current Opinion in Genetics and Development | Year: 2014

Methylation of CpG dinucleotides is a reversible modification of DNA that is highly prevalent throughout mammalian genomes. Recent advances generated genomic DNA methylation maps during cellular differentiation at unprecedented resolution. Combined with functional assays this revealed that dynamics in DNA methylation coincide with changes in regulatory activity and that transcription factors play an important role in shaping methylation patterns. This tightly links DNA methylation with underlying DNA sequence features and suggests that a substantial fraction of methylation changes occur downstream of gene regulation. Here we discuss our current understanding of the context-dependent readout of DNA methylation and criteria that need to be fulfilled for this modification to be instructive for gene regulation. © 2013 Elsevier Ltd.

Hendriks G.-J.,Friedrich Miescher Institute for Biomedical Research | Hendriks G.-J.,University of Basel | Gaidatzis D.,Friedrich Miescher Institute for Biomedical Research | Gaidatzis D.,Swiss Institute of Bioinformatics | And 3 more authors.
Molecular Cell | Year: 2014

Oscillations are a key to achieving dynamic behavior and thus occur in biological systems as diverse as the beating heart, defecating worms, and nascent somites. Here we report pervasive, large-amplitude, and phase-locked oscillations of gene expression in developing C.elegans larvae, caused by periodic transcription. Nearly one fifth of detectably expressed transcripts oscillate with an 8hr period, and hundreds change >10-fold. Oscillations are important for molting but occur in all phases, implying additional functions. Ribosome profiling reveals that periodic mRNA accumulation causes rhythmic translation, potentially facilitating transient protein accumulation as well as coordinated production of stable, complex structures such as the cuticle. Finally, large-amplitude oscillations in RNA sampled from whole worms indicate robust synchronization of gene expression programs across cells and tissues, suggesting that these oscillations will be a powerful new model to study coordinated gene expression in an animal. © 2014 Elsevier Inc.

Towbin B.D.,Friedrich Miescher Institute for Biomedical Research | Towbin B.D.,University of Basel | Gonzalez-Aguilera C.,Pablo De Olavide University | Sack R.,Friedrich Miescher Institute for Biomedical Research | And 6 more authors.
Cell | Year: 2012

The factors that sequester transcriptionally repressed heterochromatin at the nuclear periphery are currently unknown. In a genome-wide RNAi screen, we found that depletion of S-adenosylmethionine (SAM) synthetase reduces histone methylation globally and causes derepression and release of heterochromatin from the nuclear periphery in Caenorhabditis elegans embryos. Analysis of histone methyltransferases (HMTs) showed that elimination of two HMTs, MET-2 and SET-25, mimics the loss of SAM synthetase, abrogating the perinuclear attachment of heterochromatic transgenes and of native chromosomal arms rich in histone H3 lysine 9 methylation. The two HMTs target H3K9 in a consecutive fashion: MET-2, a SETDB1 homolog, mediates mono- and dimethylation, and SET-25, a previously uncharacterized HMT, deposits H3K9me3. SET-25 colocalizes with its own product in perinuclear foci, in a manner dependent on H3K9me3, but not on its catalytic domain. This colocalization suggests an autonomous, self-reinforcing mechanism for the establishment and propagation of repeat-rich heterochromatin. © 2012 Elsevier Inc.

Ecsedi M.,Friedrich Miescher Institute for Biomedical Research | Ecsedi M.,University of Basel | Grosshans H.,Friedrich Miescher Institute for Biomedical Research
Genes and Development | Year: 2013

lin-41 (lineage variant 41)/TRIM71 (tripartite motif 71) is well known for being a conserved target of the let-7 (lethal 7) microRNA (miRNA), a regulatory relationship found in animals evolutionarily as distant as Caenorhabditis elegans and humans. It has thus been studied extensively as a model for miRNA-mediated gene silencing. In contrast, the developmental and molecular functions of LIN41 have historically received less attention. However, LIN41 proteins are now emerging as important regulators of cell proliferation and differentiation in stem and progenitor cells. Moreover, LIN41's functions appear to involve two distinct molecular activities; namely, protein ubiquitylation and post-transcriptional silencing of mRNAs. Thus, LIN41 is ready for a scientific life of its own. © 2013 by Cold Spring Harbor Laboratory Press.

Bell O.,Howard Hughes Medical Institute | Tiwari V.K.,Friedrich Miescher Institute for Biomedical Research | Thoma N.H.,Friedrich Miescher Institute for Biomedical Research | Schubeler D.,Friedrich Miescher Institute for Biomedical Research | Schubeler D.,University of Basel
Nature Reviews Genetics | Year: 2011

In eukaryotes, all DNA-templated reactions occur in the context of chromatin. Nucleosome packaging inherently restricts DNA accessibility for regulatory proteins but also provides an opportunity to regulate DNA-based processes through modulating nucleosome positions and local chromatin structure. Recent advances in genome-scale methods are yielding increasingly detailed profiles of the genomic distribution of nucleosomes, their modifications and their modifiers. The picture now emerging is one in which the dynamic control of genome accessibility is governed by contributions from DNA sequence, ATP-dependent chromatin remodelling and nucleosome modifications. Here we discuss the interplay of these processes by reviewing our current understanding of how chromatin access contributes to the regulation of transcription, replication and repair. © 2011 Macmillan Publishers Limited. All rights reserved.

Oelke M.,Hannover Medical School | Bachmann A.,University of Basel | Descazeaud A.,University of Limoges | Emberton M.,University College London | And 5 more authors.
European Urology | Year: 2013

Objective: To present a summary of the 2013 version of the European Association of Urology guidelines on the treatment and follow-up of male lower urinary tract symptoms (LUTS). Evidence acquisition: We conducted a literature search in computer databases for relevant articles published between 1966 and 31 October 2012. The Oxford classification system (2001) was used to determine the level of evidence for each article and to assign the grade of recommendation for each treatment modality. Evidence synthesis: Men with mild symptoms are suitable for watchful waiting. All men with bothersome LUTS should be offered lifestyle advice prior to or concurrent with any treatment. Men with bothersome moderate-to-severe LUTS quickly benefit from α1-blockers. Men with enlarged prostates, especially those >40 ml, profit from 5α-reductase inhibitors (5-ARIs) that slowly reduce LUTS and the probability of urinary retention or the need for surgery. Antimuscarinics might be considered for patients who have predominant bladder storage symptoms. The phosphodiesterase type 5 inhibitor tadalafil can quickly reduce LUTS to a similar extent as α1-blockers, and it also improves erectile dysfunction. Desmopressin can be used in men with nocturia due to nocturnal polyuria. Treatment with an α1-blocker and 5-ARI (in men with enlarged prostates) or antimuscarinics (with persistent storage symptoms) combines the positive effects of either drug class to achieve greater efficacy. Prostate surgery is indicated in men with absolute indications or drug treatment-resistant LUTS due to benign prostatic obstruction. Transurethral resection of the prostate (TURP) is the current standard operation for men with prostates 30-80 ml, whereas open surgery or transurethral holmium laser enucleation is appropriate for men with prostates >80 ml. Alternatives for monopolar TURP include bipolar TURP and transurethral incision of the prostate (for glands <30 ml) and laser treatments. Transurethral microwave therapy and transurethral needle ablation are effective minimally invasive treatments with higher retreatment rates compared with TURP. Prostate stents are an alternative to catheterisation for men unfit for surgery. Ethanol or botulinum toxin injections into the prostate are still experimental. Conclusions: These symptom-oriented guidelines provide practical guidance for the management of men experiencing LUTS. The full version is available online ( pdf/12-Male-LUTS.pdf). © 2013 European Association of Urology.

Gillies T.E.,University of Oregon | Cabernard C.,University of Basel
Current Biology | Year: 2011

Cell division orientation during animal development can serve to correctly organize and shape tissues, create cellular diversity or both. The underlying cellular mechanism is regulated spindle orientation. Depending on the developmental context, extrinsic signals or intrinsic cues control the correct orientation of the mitotic spindle. Cell geometry has been known to be another determinant of spindle orientation and recent results have shed new light on the link between cellular shape and cell division orientation. The importance of controlling spindle orientation is manifested in neurodevelopmental defects such as microcephaly, tumor initiation as well as defects in tissue architecture and cell fate misspecification. Here, we summarize the role of oriented cell division during animal development and also outline the cellular and molecular mechanisms in selected invertebrate and vertebrate systems. © 2011 Elsevier Ltd All rights reserved.

Respiratory tract infection (RTI) involves a variety of viruses and bacteria, which can be conveniently detected by multiplex nucleic acid amplification testing (NAT). To compare the novel Luminex-based NxTAG-Respiratory Pathogen Panel (NxTAG-RPP) with the routine multiplex-ligation-NAT based RespiFinder-22® (RF-22), 282 respiratory specimens including nasopharyngeal swabs (71%), broncho-alveolar lavage (27%), throat swabs, tracheal secretions, and sputum (2%) from 116 children and 155 adults were extracted using a Corbett CAS1200 (Qiagen), and analyzed in parallel by the routine RF-22 and NxTAG-RPP. Concordant results were obtained in 263 (93.3%) cases consisting of concordant positives in 167 (59.2%) and concordant negatives in 96 (34%). Results were discordant in 19 (6.7%) consisting of 15 positive:negative, and 4 negative:positive results by NxTAG-RPP versus RF-22, respectively. Co-infections were observed in 10.3% with NxTAG-RPP and in 5.9% with RF-22. Most additional viral pathogens identified by the NxTAG-RPP involved dual infections with rhinovirus and RSV. Discordant samples were mainly due to low genome signals of Ct less than 36, when retested by QNAT suggesting a higher sensitivity of the NxTAG-RPP, also when detecting multiple infections. Hands-on time after extraction for 24 and 96 samples was 0.25 and <0.5hr for the NxTAG-RPP, and 2 and 4hr for the RF-22, respectively. The median turn-around time was 6hr (range 5-7hr) for NxTAG-RPP and 12hr (range 8-16hr) for RF-22. The NxTAG-RPP showed comparable detection rates for most respiratory pathogens, while hands-on and turn-around time were considerably shorter. The clinical significance of detecting multiple viruses needs further clinical evaluation. © 2016 Wiley Periodicals, Inc.

Gill M.E.,Friedrich Miescher Institute for Biomedical Research | Erkek S.,Friedrich Miescher Institute for Biomedical Research | Erkek S.,University of Basel | Peters A.H.F.M.,Friedrich Miescher Institute for Biomedical Research
Current Opinion in Cell Biology | Year: 2012

At fertilization, fusion of two differentiated gametes forms the zygote that is capable of forming all of the varied cell lineages of an organism. It is widely thought that the acquisition of totipotency involves extensive epigenetic reprogramming of the germline state into an embryonic state. However, recent data argue that this reprogramming is incomplete and that substantial epigenetic information passes from one generation to the next. In this review we summarize the changes in chromatin states that take place during mammalian gametogenesis and examine the evidence that early mammalian embryogenesis may be affected by inheritance of epigenetic information from the parental generation. © 2012 Elsevier Ltd.

Goetz C.,University of Basel | Goetz C.,Friedrich Miescher Institute for Biomedical Research | Pivetta C.,University of Basel | Pivetta C.,Friedrich Miescher Institute for Biomedical Research | And 2 more authors.
Neuron | Year: 2015

Movement coordination between opposite body sides relies on neuronal circuits capable of controlling muscle contractions according to motor commands. Trunk and limb muscles engage in distinctly lateralized behaviors, yet how regulatory spinal circuitry differs is less clear. Here, we intersect virus technology and mouse genetics to unravel striking distribution differences of interneurons connected to functionallydistinct motor neurons. We find that premotor interneurons conveying information to axial motor neurons reside in symmetrically balanced locations while mostly ipsilateral premotor interneurons synapse withlimb-innervating motor neurons, especially those innervating more distal muscles. We show that observed distribution differences reflect specific premotor interneuron subpopulations defined by genetic and neurotransmitter identity. Synaptic input across the midline reaches axial motor neurons preferentially through commissural axon arborization, and to a lesser extent, through midline-crossing dendrites capturing contralateral synaptic input. Together, our findings provide insight into principles of circuit organization underlying weighted lateralization of movement. © 2015 Elsevier Inc.

Baubec T.,Friedrich Miescher Institute for Biomedical Research | Colombo D.F.,Friedrich Miescher Institute for Biomedical Research | Wirbelauer C.,Friedrich Miescher Institute for Biomedical Research | Schmidt J.,Friedrich Miescher Institute for Biomedical Research | And 7 more authors.
Nature | Year: 2015

DNA methylation is an epigenetic modification associated with transcriptional repression of promoters and is essential for mammalian development. Establishment of DNA methylation is mediated by the de novo DNA methyltransferases DNMT3A and DNMT3B, whereas DNMT1 ensures maintenance of methylation through replication. Absence of these enzymes is lethal, and somatic mutations in these genes have been associated with several human diseases. How genomic DNA methylation patterns are regulated remains poorly understood, as the mechanisms that guide recruitment and activity of DNMTs in vivo are largely unknown. To gain insights into this matter we determined genomic binding and site-specific activity of the mammalian de novo DNA methyltransferases DNMT3A and DNMT3B. We show that both enzymes localize to methylated, CpG-dense regions in mouse stem cells, yet are excluded from active promoters and enhancers. By specifically measuring sites of de novo methylation, we observe that enzymatic activity reflects binding. De novo methylation increases with CpG density, yet is excluded from nucleosomes. Notably, we observed selective binding of DNMT3B to the bodies of transcribed genes, which leads to their preferential methylation. This targeting to transcribed sequences requires SETD2-mediated methylation of lysine 36 on histone H3 and a functional PWWP domain of DNMT3B. Together these findings reveal how sequence and chromatin cues guide de novo methyltransferase activity to ensure methylome integrity. ©2015 Macmillan Publishers Limited. All rights reserved.

Van Hinsbergen D.J.J.,University of Oslo | Schmid S.M.,University of Basel | Schmid S.M.,ETH Zurich
Tectonics | Year: 2012

The Aegean region (Greece, western Turkey) is one of the best studied continental extensional provinces. Here, we provide the first detailed kinematic restoration of the Aegean region since 35Ma. The region consists of stacked upper crustal slices (nappes) that reflect a complex paleogeography. These were decoupled from the subducting African-Adriatic lithospheric slab. Especially since ∼25Ma, extensional detachments cut the nappe stack and exhumed its metamorphosed portions in metamorphic core complexes. We reconstruct up to 400km of trench-perpendicular (NE-SW) extension in two stages. From 25 to 15Ma, the Aegean forearc rotated clockwise relative to the Moesian platform around Euler poles in northern Greece, accommodated by extensional detachments in the north and an inferred transfer fault SE of the Menderes massif. The majority of extension occurred after 15Ma (up to 290km) by opposite rotations of the western and eastern parts of the region. Simultaneously, the Aegean region underwent up to 650km of post-25Ma trench-parallel extension leading to dramatic crustal thinning on Crete. We restore a detachment configuration with the Mid-Cycladic Lineament representing a detachment that accommodated trench-parallel extension in the central Aegean region. Finally, we demonstrate that the Sakarya zone and Cretaceous ophiolites of Turkey cannot be traced far into the Aegean region and are likely bounded by a pre-35Ma N-S fault zone. This fault became reactivated since 25Ma as an extensional detachment located west of Lesbos Island. The paleogeographic units south of the zmir-Ankara-Sava suture, however, can be correlated from Greece to Turkey. © 2012. American Geophysical Union. All Rights Reserved.

Agency: Cordis | Branch: FP7 | Program: CPCSA | Phase: ICT-2013.9.9 | Award Amount: 74.61M | Year: 2013

This Flagship aims to take graphene and related layered materials from a state of raw potential to a point where they can revolutionize multiple industries from flexible, wearable and transparent electronics, to new energy applications and novel functional composites.\nOur main scientific and technological objectives in the different tiers of the value chain are to develop material technologies for ICT and beyond, identify new device concepts enabled by graphene and other layered materials, and integrate them to systems that provide new functionalities and open new application areas.\nThese objectives are supported by operative targets to bring together a large core consortium of European academic and industrial partners and to create a highly effective technology transfer highway, allowing industry to rapidly absorb and exploit new discoveries.\nThe Flagship will be aligned with European and national priorities to guarantee its successful long term operation and maximal impact on the national industrial and research communities.\nTogether, the scientific and technological objectives and operative targets will allow us to reach our societal goals: the Flagship will contribute to sustainable development by introducing new energy efficient and environmentally friendly products based on carbon and other abundant, safe and recyclable natural resources, and boost economic growth in Europe by creating new jobs and investment opportunities.

Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2013.2.2.1-2 | Award Amount: 8.13M | Year: 2013

Mental disorders are leading causes of disability, absence from work and premature retirement in Europe. While magnetic resonance imaging (MRI) facilities are broadly available and a vast research literature exists, few neuroimaging applications have reached clinical practice in psychiatry. A major problem is that mental illnesses are currently diagnosed as discrete entities defined clinically. Instead, recent results show that mental disorders are best understood as quantitative alterations in neural systems relevant across traditional diagnostic boundaries that reflect individual, genetic and environmental risk factors. In the IMAGEMEND consortium, we aim to discover these systems to identify the patient characteristics most relevant for treatment, derive biomarkers and decision rules from this systems-level dimensional account, and systematically validate biomarker panels in patient, high-risk and epidemiological samples to produce automated imaging-based diagnostic and predictive tests tailored for wide distribution throughout Europe in standard clinical settings. Focusing on schizophrenia, bipolar disorder and attention deficit-hyperactivity disorder, we have assembled Europes largest dataset combining neuroimaging, genetic, environmental, cognitive and clinical information on approximately 13000 participants, and have recruited international replication datasets of more than 30000 people. This unique resource will be processed using a new generation of multivariate statistical analysis to optimize existing imaging technology for the benefit of patients. We will also develop new imaging technology to enable the direct imaging-based therapeutic modification of neural circuits through rapid real-time MRI. Our deliverables will promote personalized treatment through more accurate patient stratification, allow diagnoses at the pre-symptomatic stage for early intervention and prevention, and improve prediction of treatment response and disease progression.

Agency: Cordis | Branch: H2020 | Program: SGA-RIA | Phase: FETFLAGSHIP | Award Amount: 89.00M | Year: 2016

This project is the second in the series of EC-financed parts of the Graphene Flagship. The Graphene Flagship is a 10 year research and innovation endeavour with a total project cost of 1,000,000,000 euros, funded jointly by the European Commission and member states and associated countries. The first part of the Flagship was a 30-month Collaborative Project, Coordination and Support Action (CP-CSA) under the 7th framework program (2013-2016), while this and the following parts are implemented as Core Projects under the Horizon 2020 framework. The mission of the Graphene Flagship is to take graphene and related layered materials from a state of raw potential to a point where they can revolutionise multiple industries. This will bring a new dimension to future technology a faster, thinner, stronger, flexible, and broadband revolution. Our program will put Europe firmly at the heart of the process, with a manifold return on the EU investment, both in terms of technological innovation and economic growth. To realise this vision, we have brought together a larger European consortium with about 150 partners in 23 countries. The partners represent academia, research institutes and industries, which work closely together in 15 technical work packages and five supporting work packages covering the entire value chain from materials to components and systems. As time progresses, the centre of gravity of the Flagship moves towards applications, which is reflected in the increasing importance of the higher - system - levels of the value chain. In this first core project the main focus is on components and initial system level tasks. The first core project is divided into 4 divisions, which in turn comprise 3 to 5 work packages on related topics. A fifth, external division acts as a link to the parts of the Flagship that are funded by the member states and associated countries, or by other funding sources. This creates a collaborative framework for the entire Flagship.

Agency: Cordis | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-2013-ITN | Award Amount: 3.97M | Year: 2013

COMIQ (COld Molecular Ions at the Quantum limit) will investigate how cooling, trapping, and control techniques applied molecular ion can expand the realm of quantum technology, enhance precision meaurements on molecular systems and lead to chemistry at the ultracold quantum limit.

Agency: Cordis | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2015-ETN | Award Amount: 3.90M | Year: 2015

The Phosphoinositide 3-kinase (PI3K) pathway is at the core of multiple fundamental biological processes controlling metabolism, protein synthesis, cell growth, survival, and migration. This inevitably leads to the involvement of the PI3K signalling pathway in a number of different diseases, ranging from inflammation and diabetes to cancer, with PI3K pathway alterations present in almost 80% of human cancers. Therefore, PI3Ks have emerged as important targets for drug discovery and, during 2014, the first PI3K inhibitor was approved by FDA in the US for the treatment of a lymphocytic leukaemia. Nonetheless, our understanding of PI3K-mediated signalling is still poor and only a fraction of the potential therapeutic applications have been addressed so far, leaving a large amount of translational work unexplored. Europe features a set of top quality research institutions and pharmaceutical companies focused on PI3K studies but their activities have been so far scattered. This proposal fills this gap by providing a multidisciplinary network (biochemistry, mouse studies, disease models, drug development, software development) and an unprecedented training opportunity from the bench to the bedside (from pre-clinical discoveries to clinical trials), through cutting edge molecular biology, drug discovery and clinical trial organization. The proposal is aimed at training young investigators in deep understanding of the different PI3K isoforms in distinct tissues and to translate this knowledge into a new generation of PI3K inhibitors, treatment modalities and into identify new uses for existing PI3K inhibitors.

Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: HEALTH-2009-2.3.2-3 | Award Amount: 17.07M | Year: 2010

This proposal is for a large scale collaborative project in which we propose both to develop novel microbicides directed against new intracellular targets and to investigate novel combinations of highly active anti-retroviral drugs which may be particularly effective as microbicides. Combinations may enhance efficacy but equally importantly will increase the genetic barrier to the development of resistance. The proposal includes development of both slow release and gel formulations, pharmacokinetic and challenge experiments in macaques as well as human studies including a collaborative study with an EDCTP-funded project to use multiplex and proteomic technologies as well as culture-independent DNA-based analysis of mucosal microbiota to investigate biomarkers and establish a baseline signature from which perturbations can be recognised. This is a large consortium comprising 30 partners from 8 EU countries and from Switzerland, Ukraine, South Africa and the United States.Partners include microbicide developers, IPM and Particle Sciences, and producers, Gilead, Tibotec and Virco. Two SMEs will also participate in RTD aspects. The consortium is multidisciplinary with scientists engaged in basic discovery working with new targets and developing novel chemistry to produce compounds with improved safety and efficacy profiles as well as altered patterns of resistance.

Agency: Cordis | Branch: H2020 | Program: RIA | Phase: NMP-26-2014 | Award Amount: 11.93M | Year: 2015

One of the greatest challenges facing regulators in the ever changing landscape of novel nano-materials is how to design and implement a regulatory process which is robust enough to deal with a rapidly diversifying system of manufactured nanomaterials (MNM) over time. Not only does the complexity of the MNM present a problem for regulators, the validity of data decreases with time, so that the well-known principle of the half-life of facts (Samuel Arbesman, 2012) means that what is an accepted truth now is no longer valid in 20 or 30 years time. The challenge is to build a regulatory system which is flexible enough to be able to deal with new targets and requirements in the future, and this can be helped by the development and introduction of Safe by Design (SbD) principles. The credibility of such a regulatory system, underpinned by the implementation of SbD, is essential for industry, who while accepting the need for regulation demand it is done in a cost effective and rapid manner. The NANoREG II project, built around the challenge of coupling SbD to the regulatory process, will demonstrate and establish new principles and ideas based on data from value chain implementation studies to establish SbD as a fundamental pillar in the validation of a novel MNM. It is widely recognized by industries as well as by regulatory agencies that grouping strategies for NM are urgently needed. ECETOC has formed a task force on NM grouping and also within the OECD WPMN a group works on NM categorisation. However, so far no reliable and regulatory accepted grouping concepts could be established. Grouping concepts that will be developed by NanoREG II can be regarded as a major innovation therefore as guidance documents on NM grouping will not only support industries or regulatory agencies but would also strongly support commercial launch of new NM.

Agency: Cordis | Branch: FP7 | Program: MC-IRSES | Phase: FP7-PEOPLE-2011-IRSES | Award Amount: 314.70K | Year: 2012

The main goal of this project is the establishment of a network between European, South American, North American and South African educational and research entities. This attempt will be based on an innovative scientific project aiming towards the identification of hERG (human Ether--go-go Related Gene) channel blockers in commonly consumed botanicals and supplements. Blocking these ion channels may result in ventricular tachyarrhythmia and an increased incidence of sudden death. Thus, the hERG channel is considered as an important antitarget. Several drugs have been removed from the market for this reason, and compounds have been blocked from proceeding further into phases of clinical development. As botanicals (comprising dietary supplements, spices, herbal medicinal products) continue to increase in popularity there is an urgent need for studies aimed to critically assess the potential cardiotoxic risks of these products. State-of-the-art methodologies and techniques will be incorporated for target-oriented identification and isolation of hERG channel blocking constituents. PK and PD studies will be performed and LC-MS based methods will be developed and applied towards the measurement of bioactive components in biofluids samples. Comparison of biofluids derived from administration of single chemical entities and corresponding botanicals will be achieved using MS- and NMR-based metabolomics. The obtained results will help to elaborate and evaluate hERG related safety aspects aiming towards the risk assessment of frequently consumed botanicals. Within this frame numerous short term and extended secondments of scientific staff will be accomplished, while the organization of several workshops will assure the proper dissemination of the produced knowledge throughout all the scientific community but also the public. Core scientific knowledge is expected to be produced and exchanged, and partnerships with future scientific potentials to be created.

Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: HEALTH-2007-2.1.1-5 | Award Amount: 15.72M | Year: 2008

The European Drug Initiative on Channels and Transporters, EDICT, allies for the first time, partners with world-class expertise in both the structural and functional characterisation of membrane channels and transporters. State-of-the-art facilities and personnel for X-ray crystallography, Electron Microscopy and Nuclear Magnetic Resonance and the latest throughput technology, will provide infrastructure for scientists characterising channel and transport functions in man and pathogenic microorganisms. Our experts in the analyses of all the databases of these membrane proteins and molecular modelling will work with our industrial partners on specific targets chosen for their potential to improve the health of European citizens, increase the competitiveness of European health-related industries and businesses and address global health issues. EDICT will increase knowledge of biological processes and mechanisms involved in normal health and in specific disease situations, and transpose this knowledge into clinical applications. By combining computational and experimental analyses, existing detailed molecular models of channel and transporter proteins, and novel structures derived by our partners, will be analysed to identify the critical regions constituting drug targets. These basic discoveries will be translated via in silico and experimental strategies with our industrial partners into the design of novel drugs that modify activities of the membrane proteins for the benefit of the patients. The range of human proteins covered includes potassium channels, anion and cation transporters, neurotransmitter transporters, cation-transporting ATPases and mitochondrial transporters. Structures of bacterial homologues to the human proteins are exploited to inform the studies of their human counterparts

Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH-2007-2.2.1-3 | Award Amount: 3.79M | Year: 2008

GABAergic and serotoninergic systems are key players in the control of anxiety states but the precise bases for their action has remained elusive. New findings, brought about by members of this consortium, are radically changing our views on the neurobiological action of these two transmitters and will be the focus of the present proposal. The first original dimension is the discovery of a developmental role of serotonin (5-HT) in the genesis of anxiety disorders, and the finding of interactions between 5-HT-related genes and environmental risk factors. The second new dimension is the discovery that metabotropic GABA-B receptors play a critical role in mediating the anxiolytic effects of GABA, a starting point for the conception and design of novel therapeutic approaches. Finally, recent evidence point to strong reciprocal interactions between the two systems. In this proposal , researchers that are at the forefront of these research domains will build on and extend these promising new findings. The project associates specialists of development, neuronal plasticity, neurobehaviour, neuropharmacology and mouse genetics. The consortium will explore the neuronal circuits mediating the developmental effects of 5-HT by using existing models and by creating new models for site- and time-specific invalidation of 5-HT related genes (Tph2, pet1,VMAT2,5-HT1A-R), focusing on the hippocampus, amygdala and raphe nuclei. They will explore the role of GABA-B receptors in anxiety and the interaction of these receptors with the 5-HT system. The developmental effects of GABA-B receptors and a new generation of GABA-B modulators that produce anxiolytic effects in animal models will be explored. Finally they will investigate how exposure to adverse environments interacts with 5-HT-genes and GABA-B receptor genes to produce anxiety phenotypes. The proposal will bring new knowledge on the neurobiological basis of anxiety, and open up novel therapeutic approaches in anxiety disorders

Agency: Cordis | Branch: H2020 | Program: RIA | Phase: INFRAIA-1-2014-2015 | Award Amount: 12.17M | Year: 2015

The overall objective will be to create and mobilise an International network of high calibre centres around a strong European group of institutes selected for their appropriate expertises, to collect, amplify, characterise, standardise, authenticate, distribute and track, mammalian and other exotic viruses. The network of EVAg laboratories including 25 institutions represents an extensive range of virological disciplines. The architecture of the consortium is based on the association of capacities accessible to the partners but also to any end-users through the EVAg web-based catalogue. This concept has been elaborated and tested for its efficiency during the successful EVA project (FP7). The project will integrate more facilities dedicated to high risk pathogen (HRP) manipulation (1 in EVA, 13 in EVAg) The access to products derived from those HRP will be enhanced and for instance the production of diagnostic reagents will be facilitated. The new project will also provide access to high containment biosafety facilities to carry out in vivo studies of infectious disease using natural or models hosts, to look at prophylactic or therapeutic control measures and to develop materials for the evaluation of diagnostic tests, meaning an extensive capacity to service and to training. EVAg will also link up with other network-based virus-associated programmes that exist globally. However, looking further ahead, EVAg is conceived ultimately to be an open entity aiming at developing synergies and complementarity capabilities in such a way as to offer an improved access to researchers. This project will generate the largest collection of mammalian viruses in the world and move beyond the current state-of-the-art to provide an increasingly valuable resource and service to the worlds scientific community, including government health departments, higher education institutes, industry and, through information systems, the general public.

Agency: Cordis | Branch: H2020 | Program: RIA | Phase: PHC-08-2014 | Award Amount: 25.06M | Year: 2015

The TBVAC2020 proposal builds on the highly successful and long-standing collaborations in subsequent EC-FP5-, FP6- and FP7-funded TB vaccine and biomarker projects, but also brings in a large number of new key partners from excellent laboratories from Europe, USA, Asia, Africa and Australia, many of which are global leaders in the TB field. This was initiated by launching an open call for Expressions of Interest (EoI) prior to this application and to which interested parties could respond. In total, 115 EoIs were received and ranked by the TBVI Steering Committee using proposed H2020 evaluation criteria. This led to the prioritisation of 52 R&D approaches included in this proposal. TBVAC2020 aims to innovate and diversify the current TB vaccine and biomarker pipeline while at the same time applying portfolio management using gating and priority setting criteria to select as early as possible the most promising TB vaccine candidates, and accelerate their development. TBVAC2020 proposes to achieve this by combining creative bottom-up approaches for vaccine discovery (WP1), new preclinical models addressing clinical challenges (WP2) and identification and characterisation of correlates of protection (WP5) with a directive top-down portfolio management approach aiming to select the most promising TB vaccine candidates by their comparative evaluation using objective gating and priority setting criteria (WP6) and by supporting direct, head-to head or comparative preclinical and early clinical evaluation (WP3, WP4). This approach will both innovate and diversify the existing TB vaccine and biomarker pipeline as well as accelerate development of most promising TB vaccine candidates through early development stages. The proposed approach and involvement of many internationally leading groups in the TB vaccine and biomarker area in TBVAC2020 fully aligns with the Global TB Vaccine Partnerships (GTBVP).

Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH-2007-3.2-4 | Award Amount: 3.83M | Year: 2009

Current human resources planning models in nursing are unreliable and ineffective as they consider volumes, but ignore effects on quality in patient care. The project RN4CAST aims innovative forecasting methods by addressing not only volumes, but quality of nursing staff as well as quality of patient care. RN4CAST is a consortium of 15 partners that will quantify in 11 European countries-Belgium, Finland, Germany, Greece, Ireland, Poland, Spain, Sweden, Switzerland, Netherlands, UK - important unmeasured factors in forecasting models including how features of hospital work environments and qualifications of the nurse workforce impact on nurse recruitment, retention, productivity and patient outcomes. Three partners outside Europe - China, South Africa, and Botswana- provide additional perspectives. Innovative elements of the project include unique measures of workplace dynamics and patient outcomes. Nurse workforce planning initiatives at national and European levels will be reviewed and newly collected data added to enhance accuracy for nurse workforce management. Data collection focuses on general hospitals, which employ the majority of nurses, account for the largest number of medical errors and comprise the largest share of national health expenditures. Each European partner will conduct a study of 20 to 50 hospitals depending on country size yielding information on more than 350 hospitals including surveys from over 50,000 nurses and outcomes of tens of thousands of patients. European partners were selected by geographic distribution, membership duration in the EU, research expertise and availability of patient discharge data. University of Pennsylvania, USA, will contribute specialized research expertise derived from previous international research. RN4CAST will be the largest nurse workforce study ever conducted in Europe, will add to accuracy of forecasting models and generate new approaches to more effective management of nursing resources in Europe.

Agency: Cordis | Branch: H2020 | Program: SGA-RIA | Phase: FETFLAGSHIP | Award Amount: 89.00M | Year: 2016

Understanding the human brain is one of the greatest scientific challenges of our time. Such an understanding can provide profound insights into our humanity, leading to fundamentally new computing technologies, and transforming the diagnosis and treatment of brain disorders. Modern ICT brings this prospect within reach. The HBP Flagship Initiative (HBP) thus proposes a unique strategy that uses ICT to integrate neuroscience data from around the world, to develop a unified multi-level understanding of the brain and diseases, and ultimately to emulate its computational capabilities. The goal is to catalyze a global collaborative effort. During the HBPs first Specific Grant Agreement (SGA1), the HBP Core Project will outline the basis for building and operating a tightly integrated Research Infrastructure, providing HBP researchers and the scientific Community with unique resources and capabilities. Partnering Projects will enable independent research groups to expand the capabilities of the HBP Platforms, in order to use them to address otherwise intractable problems in neuroscience, computing and medicine in the future. In addition, collaborations with other national, European and international initiatives will create synergies, maximizing returns on research investment. SGA1 covers the detailed steps that will be taken to move the HBP closer to achieving its ambitious Flagship Objectives.

Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: NMP.2010.2.2-1 | Award Amount: 3.98M | Year: 2011

Functional organic molecules and metal and semiconductor nanocrystals represent attractive building blocks due to their composition-, size- and structure-dependent electronic properties, and the ability to design and manipulate these properties via low-cost and established chemical synthesis. Building from the pressing need of the European market to develop novel, scalable and cheaper technologies for sensing applications, the main objective of the HYSENS project is to exploit inexpensive organic functional molecules and inorganic nanocrystals as building blocks to synthesize novel high-knowledge materials for the development of sensors for Group I, II transition metal cations and anions (Cl-, NO3-). The hybrid material intelligence resulting from the engineered combination of individual units will allow the execution of logic functions able to reduce false sensing outputs towards the development of sensors with enhanced selectivity and sensitivity. Our goal is to elucidate the mechanisms governing the optical and electrical response of such engineered hybrid materials arising from the interaction between the organic functional molecule component and the inorganic nanocrystal core component. Establishment of component-function relationships will lead to disruptive new knowledge that will impact on optical and electrical sensors technologies.

Agency: Cordis | Branch: H2020 | Program: ERC-ADG | Phase: ERC-ADG-2015 | Award Amount: 2.50M | Year: 2016

Breast cancer is diagnosed in ~1.4 million women worldwide and ~500,000 lives are lost to the disease annually. Patients may do well after surgery and initial treatment, but drug resistant and fatal metastases often develop. Improved treatment options are urgently needed. The connecting thread of this project is the identification of epigenetic drivers of breast cell fate, tumor heterogeneity and metastasis. Tumor heterogeneity impinges on prognosis, response to therapy, and metastasis and is one of the most important and clinically relevant areas of cancer research. Tumor heterogeneity results from genetic and epigenetic alterations that enhance the plasticity and fitness of cancer cells in the face of hurdles like the metastatic cascade and anti-cancer therapies. Unfortunately, the driving molecular mechanisms remain unclear, particularly the potential interplay between signalling pathways and epigenetic programs. This interdisciplinary project uses pathophysiologically relevant models and state-of-the-art technologies to identify molecular mechanisms underlying crosstalk between key signalling pathways and epigenetic programs in the normal and neoplastic breast. We hypothesize that interfering with these programs will decrease tumor heterogeneity. We will address the effects of: - SHP2/ERK signalling on the epigenetic programs of tumor-initiating cells (Aim 1) - PI3K pathway hyperactivation on the epigenetic programs underpinning cell plasticity (Aim 2) - Epigenetic regulators on normal mammary cell self-renewal and on metastasis (Aim 3) By investigating the integrated effects of key signalling pathways and epigenetic programs in normal and neoplastic breast, this multipronged project will identify and validate mechanisms of cell plasticity. The derived mechanistic understanding will generate means to interfere with tumor heterogeneity and thus improve the efficacy of anti-cancer therapies and ultimately the clinical outcome for patients with breast cancer.

Agency: Cordis | Branch: FP7 | Program: CP | Phase: ICT-2009.8.2 | Award Amount: 9.14M | Year: 2010

The overall objectives of the AQUTE project are\nA) To develop quantum technologies based on atomic, molecular and optical (AMO) systems for\n* scalable quantum computation;\n* entanglement-enabled technologies like metrology and sensing.\nB) To establish and exploit new interdisciplinary connections, coming from AMO physics, but also including concepts and experimental settings of solid state systems, in order to\n* reinforce interdisciplinary links at the frontiers of quantum information science, and other fields of physics or science in general;\n* conceive and realize novel hybrid systems that couple in a coherent way physically different quantum degrees of freedom.\nObj. A will be pursued along two complementary directions:\n* a bottom-up approach, where individually trapped atomic particles are combined into elementary general-purpose quantum processors including qubit interconnects;\n* a top-down approach, where many-particle atomic systems are employed to realize special-purpose quantum processors, for instance quantum simulators.\nGroundbreaking work in qualitatively new directions is also needed to lay the foundations for the future attainment of scalable fault-tolerant architectures. AQUTE will thus also\n* investigate new experimental systems that have become available in the laboratory and are of direct relevance for QIFT;\n* optimize existing and develop novel theoretical concepts for quantum processing.\nObj. B connects atomic quantum technologies for QIFT to a wider context, by\n* exploring hybrid approaches to QIFT beyond AMO physics;\n* improving connections between QIFT and science in general, following the emergence of a new quantum paradigm at the frontier of nanosciences and information sciences.\nThese research lines determine the structuring of the AQUTE workplan into four deeply interrelated Sub-Projects: Entangling gates and quantum processors, Hybrid quantum systems and interconnects, Quantum Simulators and Quantum Technologies.

Agency: Cordis | Branch: H2020 | Program: RIA | Phase: PHC-11-2015 | Award Amount: 7.42M | Year: 2016

Cancer is the second leading cause of mortality in EU member states with ~90% of all cancer deaths caused by metastatic spread. Despite its significance, measuring metastatic potential as well as potential indicators of therapy efficacy remain unmet clinical challenges. Recently, it has been demonstrated in vitro, that aggressive metastatic cells pull on their surroundings suggesting that metastatic potential could be gauged by measuring the forces exert by tumours. Furthermore, many solid tumours show a significantly increased interstitial fluid pressure (IFP) which prevents the efficient uptake of therapeutic agents. As a result, a reduction in IFP is recognized as a hallmark of therapeutic efficacy. Currently, there is no non-invasive modality that can directly image these forces in vivo. Our objective is the non-invasive measurement of both IFP within tumours as well as the forces they exert on their surrounding environment. This will be used to predict a tumours metastatic potential and importantly, changes in these forces will be used to predict the therapeutic efficacy of drug therapy. To attain this goal, the biomechanical properties of the tumour and its neighbouring tissue will be measured via MR-elastography at various measured deformation states. Resultant images will be used to reconstruct images of the internal and external forces acting on the tumour. We call this novel imaging modality Magnetic Resonance Force (MRF) imaging. We will calibrate MRF via cell cultures and pre-clinical models, and then test the method in breast, liver, and brain cancer patients. Thereby, we will investigate whether MRF data can predict metastatic spread and measure IFP in patients. We will also investigate the potential to non-invasively modulate the force environment of cancer cells via externally applied shear forces with the aim of impacting cell motility and proliferation. This can provide novel mechanism for anticancer therapeutic agents via mechanotransduction.

Friedrich Miescher Institute for Biomedical Research and University of Basel | Date: 2015-02-26

The application relates to a method for predicting a risk for preeclampsia in a subject, said method comprising analysing a sample from the subject for the level of expression of miR455 and comparing the level of expression of miR455 in the sample from the subject to the levels of miR455 in a control sample, wherein a significantly lower expression of miR455 as compared to the expression of miR455 in the control is indicative of a risk for preeclampsia.

Scharer L.,University of Basel | Pen I.,University of Groningen
Philosophical Transactions of the Royal Society B: Biological Sciences | Year: 2013

Sex allocation theory predicts the optimal allocation to male and female reproduction in sexual organisms. In animals, most work on sex allocation has focused on species with separate sexes and our understanding of simultaneous hermaphrodites is patchier. Recent theory predicts that sex allocation in simultaneous hermaphrodites should strongly be affected by post-copulatory sexual selection, while the role of pre-copulatory sexual selection is much less clear. Here, we review sex allocation and sexual selection theory for simultaneous hermaphrodites, and identify several strong and potentially unwarranted assumptions. We then present a model that treats allocation to sexually selected traits as components of sex allocation and explore patterns of allocation when some of these assumptions are relaxed. For example, when investment into a male sexually selected trait leads to skews in sperm competition, causing local sperm competition, this is expected to lead to a reduced allocation to sperm production. We conclude that understanding the evolution of sex allocation in simultaneous hermaphrodites requires detailed knowledge of the different sexual selection processes and their relative importance. However, little is currently known quantitatively about sexual selection in simultaneous hermaphrodites, about what the underlying traits are, and about what drives and constrains their evolution. Future work should therefore aim at quantifying sexual selection and identifying the underlying traits along the pre-to post-copulatory axis. © 2013 The Author(s) Published by the Royal Society. All rights reserved.

Baubec T.,Friedrich Miescher Institute for Biomedical Research | Ivanek R.,Friedrich Miescher Institute for Biomedical Research | Lienert F.,Friedrich Miescher Institute for Biomedical Research | Schubeler D.,Friedrich Miescher Institute for Biomedical Research | Schubeler D.,University of Basel
Cell | Year: 2013

To gain insight into the cellular readout of DNA methylation, we established a strategy for systematically profiling the genome-wide distribution of chromatin-interacting factors. This enabled us to create genomic maps for the methyl-CpG-binding domain (MBD) family of proteins, including disease-relevant mutants, deletions, and isoforms. In vivo binding of MBD proteins occurs predominantly as a linear function of local methylation density, requiring functional MBD domains and methyl-CPGs. This interaction directs specificity of MBD proteins to methylated, CpG-dense, and inactive regulatory regions. In contrast, binding to unmethylated sites varies between MBD proteins and is mediated via alternative domains or protein-protein interactions. Such targeting is exemplified by NuRD-complex-mediated tethering of MBD2 to a subset of unmethylated, active regulatory regions. Interestingly, MBD3 also occupies these sites, but like MBD2, binding is independent of the presence of hydroxymethylation. These functional binding maps reveal methylation-dependent and -independent binding modes and revise current models of DNA methylation readout through MBD proteins. © 2013 Elsevier Inc.

Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2012.2.4.4-2 | Award Amount: 3.79M | Year: 2012

The current approach to diagnosis and management of the rare disease systemic sclerosis (SSc) is based on American College of Rheumatology criteria with low sensitivity and few validated recommendations for the therapy of the disease and its manifold organ manifestations. To overcome these shortcomings, the DeSScipher project will use the multinational, prospective and open EUSTAR (Scleroderma Trials and Research group of the European League Against Rheumatism) SSc cohort based on the established MEDSonline database which covers >30 data items and will evolve into a multimodular tool to answer step-by-step all immanent questions in a long-term setting according to the nature of the disease. The resulting progress will address functionally disabling manifestations affecting the hands (digital ulcers and arthritis), and compare the efficacy and safety of off-label drugs in the treatment of vital organ manifestations. Specifically, the DeSScipher project will evaluate (i) the utility of a combination of easy-to-perform clinical and laboratory investigations in combination with capillaroscopy for identifying SSc patients at risk for the development of digital ulcers at an early stage (ii) the prevention and treatment of digital ulcers and hand arthritis in order to improve long-term disability and quality of life, (iii) the efficacy of different immunosuppressive agents in attenuating or inhibiting pulmonary fibrosis, (iv) the optimal treatment options for reducing morbidity and mortality of pulmonary hypertension and severe heart disease in SSc. Based on the results of these observational trials, the DeSScipher project will develop evidence-based clinical guidelines for the future management of adult and juvenile SSc to be disseminated widely and rapidly to physicians and patients. Novel outcome measures will also be provided as a basis for future clinical trials.

Agency: Cordis | Branch: FP7 | Program: MC-ITN | Phase: PEOPLE-2007-1-1-ITN | Award Amount: 5.80M | Year: 2008

Membrane proteins (MPs) are known to be key molecules in cellular communications, from signal transduction to transport of ions, metabolites and other molecules. They also participate in the synthesis of ATP, the import of soluble or MPs from the cytosol, and they protect living organisms from toxic factors. The proposal consists in a joint training effort involving the major biophysical methods that are -or soon will be- the major techniques used in the field of structural biology of MPs. A collaborative effort is essential for the training of the future generation of biologists dedicated to membrane proteins. It will pave the way to an integrative approach for the study of structure-function relationships of membranes. It will therefore open new strategies for structure-based drug design, in particular toward G-protein coupled receptors (GPCR), which are major drug targets (GPCRs represent 30% of current drug targets). The training proposed in this program will not only form high-level academic researchers but will also largely contribute in forming the main actors of the future developments in biotechnology and personalized medicine. This network combines 12 academic research groups and 3 industrial companies interested in collaborating with these groups and involved in drug discovery or scientific equipment for SBMP. These groups are internationally recognized for analysing the structure and dynamics of membrane proteins by a combination of experimental and theoretical approaches: in vivo and in vitro expressions systems, functional/biochemical/biophysical characterisation, X-Ray diffraction, electron microscopy (EM), atomic force microscopy (AFM), single-molecule force spectroscopy (SMFS), liquid and solid state NMR, numerical simulations. Seven partners from 6 different countries are involved: France, Poland, Portugal, Switzerland, Germany and the Netherlands.

Agency: Cordis | Branch: FP7 | Program: CPCSA | Phase: ICT-2013.9.9 | Award Amount: 72.73M | Year: 2013

Understanding the human brain is one of the greatest challenges facing 21st century science. If we can rise to the challenge, we can gain profound insights into what makes us human, develop new treatments for brain diseases and build revolutionary new computing technologies. Today, for the first time, modern ICT has brought these goals within sight. The goal of the Human Brain Project, part of the FET Flagship Programme, is to translate this vision into reality, using ICT as a catalyst for a global collaborative effort to understand the human brain and its diseases and ultimately to emulate its computational capabilities. The Human Brain Project will last ten years and will consist of a ramp-up phase (from month 1 to month 36) and subsequent operational phases.\nThis Grant Agreement covers the ramp-up phase. During this phase the strategic goals of the project will be to design, develop and deploy the first versions of six ICT platforms dedicated to Neuroinformatics, Brain Simulation, High Performance Computing, Medical Informatics, Neuromorphic Computing and Neurorobotics, and create a user community of research groups from within and outside the HBP, set up a European Institute for Theoretical Neuroscience, complete a set of pilot projects providing a first demonstration of the scientific value of the platforms and the Institute, develop the scientific and technological capabilities required by future versions of the platforms, implement a policy of Responsible Innovation, and a programme of transdisciplinary education, and develop a framework for collaboration that links the partners under strong scientific leadership and professional project management, providing a coherent European approach and ensuring effective alignment of regional, national and European research and programmes. The project work plan is organized in the form of thirteen subprojects, each dedicated to a specific area of activity.\nA significant part of the budget will be used for competitive calls to complement the collective skills of the Consortium with additional expertise.

Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: ENV.2009. | Award Amount: 3.92M | Year: 2009

Public exposure to electromagnetic fields in the radio frequency spectrum has increased dramatically in the last two decades. Although research has mainly focused on the exposure and health risk evaluations of cellular networks and mobile phones in recent years, studies on the effects of the pervasive and prolonged EMF exposure on human health due to the exponential growth of wireless network device usage in homes, offices and schools are lacking. The proposed project SEAWIND aims (1) to provide a comprehensive assessment of the incident field exposure in typical living scenarios such as in homes, offices and classrooms by installed wireless local area networks (WLAN or WiFi) or wireless metropolitan area networks (WMAN or WiMAX), body-mounted and body-worn wireless personal area networks (WPAN) and WLAN devices, and specific wireless applications in industry, e.g., novel RFID logistic applications; (2) to numerically determine the induced fields in the human body using a set of models representing the human population; and (3) to screen potential biological sensitivities at the molecular, developmental and functional levels in cells. The necessary technology will also be developed to accurately assess the exposures for device compliance testing and to accurately assess in situ exposures. The comprehensive risk assessment will be based on the findings of this project, addressing the specificity of the exposure of wireless networks combined with the current body of literature on biological interactions of EMF covering the entire radio-frequency spectrum. A comparison to other exposures such as cellular mobile devices, base stations, TV, Radio, etc will also be included.

Agency: Cordis | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-2011-ITN | Award Amount: 4.25M | Year: 2011

RNA molecules are at the heart of life. It is now commonly admitted that nearly all the human genome is transcribed, and a wealth of new coding and non-coding RNAs have been discovered. Importantly, modern RNAs are never naked, but always exist in complex with proteins to form RNPs (Ribonucleoproteins). In the case of non-coding RNAs, these proteins are usually stably associated with the RNA and help to perform their function. In contrast, RNA binding proteins are usually transiently bound to coding RNAs, and control various aspects of their metabolism. For the next generation of scientists, a great challenge will be to understand the function and the mechanisms of action of the myriads of RNPs. The goal of this ITN (RNPnet) is first to bring together existing labs from different discipline, to join forces and tackle key questions in the field, and second, to produce highly-trained young researchers that will be sensitized to RNA and possess a multidisciplinary approach to research. The multiple expertises present in the fifteen labs of this network will be used in a highly cooperative and integrated manner. The research training will focus on studying RNPs involved in mRNA surveillance, splicing and editing. In addition, a total of fifteen meetings including two summer schools and several workshops are planed to strengthen education and interaction among participants of RNPnet. Finally, another important aspect of RNPnet is the presence of two industrial partners. Their aim is to use the enormous potential of RNA biology in therapeutic applications, either by modifying RNAs and using it as a drug, or by targeting specific RNA binding proteins with small molecules. We foresee that the presence of industrial partners will be highly beneficial for the students, and that, by exposing them to both the academic and industrial world, we will both facilitate communication between these worlds and provide to the young trainees a large panorama of their possible career.

Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: NMP-2007-1.1-2 | Award Amount: 5.00M | Year: 2008

Recent developments in the design and synthesis of nanoscale building blocks as active elements in opto- or bio-electronic devices with tailored electronic functionality have the potential to open up new horizons in nanoscience and also revolutionise multi-billion dollar markets across multiple technology sectors including healthcare, printable electronics, and security. Ligand-stabilised inorganic nanocrystals (~2-30 nm core diameters) and functional organic molecules are attractive building blocks due to their size dependent opto-electronic properties, the availability of low-cost synthesis processes and the potential for formation of ordered structures via (bio) molecular recognition and self-assembly. Harnessing the complementary properties of both nanocrystals and functional molecules thus represents a unique opportunity for generation of new knowledge and development of new classes of high knowledge-content materials with specific functionality tailored for key applications, e.g., printable electronics, biosensing or energy conversion in the medium term, and radically new information and signal processing paradigms in the long term. Self-assembly and self-organisation processes offer the potential to achieve dimensional control of novel multifunctional materials at length scales not accessible to conventional top-down technologies based on lithography. It is critical for European industry to develop new knowledge and low-cost, scaleable processes for assembly and electrical interfacing of these multifunctional materials with conventional contact electrodes in order to produce into tailored devices and products, in particular on low-cost substrates. The FUNMOL consortium will deliver substantial innovation to European industry via development of cost-effective, scaleable processes for directed assembly of high-knowledge content nanocrystal-molecule materials into electrically-interfaced devices at silicon oxide, glass and plastic substrates.

Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH-2007-3.1-4 | Award Amount: 3.83M | Year: 2009

The main objective of the proposed project is to develop and to validate a system for measurement and feedback of outcome quality and support of decision making. The project will be executed in the areas of postoperative pain management which serves as an example for other fields of medicine with a high variation of care. The project will provide the medical community with a unique, user-friendly system to improve treatment of patients with postoperative pain. We propose to develop and implement a web-based information system, featuring three functions: Feedback and benchmarking system which provides participating sites with continuously updating data and analyses about the quality of care they provide compared to other institutions and allows identification of best clinical practice. Clinical Decision Support System for Post-Operative Pain, which responds to queries made by physicians for advice regarding treatment of individual patients. A Knowledge Library which provides clinicians with easily accessible summaries of evidence-based recommendations tailored to specific post-operative situations. The first two functions will draw their information from a large database or registry. The registry will receive data about post-operative patients from x participating clinical sites across Europe. The third function, the Knowledge Library, will draw its information from published, peer-reviewed studies, and will be updated periodically. To increase the benefit of the system to end-users, the registry will be complemented with patient data on side effects and treatment costs. All of these will be integrated into the feedback system. The proposed project is the first comprehensive, concerted European effort in the field of improving clinical decision making. It integrates experience gained from national initiatives, and the expertise of world-leading, European-based, groups dealing with benchmarking, health outcomes and health care utilization research

Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: ENV.2007. | Award Amount: 4.10M | Year: 2008

Like any living system, urban communities consume material and energy inputs, process them into usable forms, and eliminate the wastes from the process. This can be seen as metabolism of industry, commerce, municipal operations, and households. Understanding the pattern of these energy and material flows through a communitys economy provides a systemic reading of the present situation for goal and objective setting and development of indicators for sustainability. At present, planning policies often reflect the logic of the market. They would better reflect a vision of urban development, in which environmental and social considerations are fully embedded in spatial planning policies at all steps of the policy cycle from problem identification and policy design through to the implementation and ex-post evaluation stages. Therefore, the widespread inclusion of sustainability objectives in urban planning at all scales (from regional to site level) is necessary, providing the opportunity for the incorporation of bio-physical sciences knowledge into the planning process on a routine basis. To this end, the proposed project BRIDGE (sustainaBle uRban plannIng Decision support accountinG for urban mEtabolism) aims at bridging the gap between bio-physical sciences and urban planners and to illustrate the advantages of accounting for environmental issues on a routine basis in design decisions. BRIDGE will provide the means to quantitative estimate the various components of the urban metabolism (observation of physical flows and modelling), the means for quantitative estimate their impacts (socio-economic and environmental impact assessments and indicators), as well as the means for resource optimisation in urban fabric (support the decision making in urban planning). BRIDGE will focus on the interrelation between energy and material flows and urban structure.

Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: ENV.2007. | Award Amount: 8.22M | Year: 2008

European policy making is hampered by considerable uncertainty about the magnitude and nature of the impacts of long term exposure to air pollution on human health. ESCAPE is a collaboration of more than 30 European cohort studies including some 900,000 subjects. It is aimed at quantifying health impacts of air pollution and at reducing uncertainty. ESCAPE will also test new hypotheses on specific health effects of air pollution. ESCAPE will focus on effects of within-city, within-area and within-country contrasts in air pollution, and so will enable Europe to remain at the cutting edge worldwide for further development and application of methods which have been largely pioneered here. ESCAPE will make measurements of airborne particulate matter and nitrogen oxides in selected regions in Europe. It will measure the chemical composition of the collected particles and it will store samples for future chemical and toxicological analyses. Escape will focus on four categories of cohort studies: 1. Pregnancy outcome and birth cohort studies; 2. Studies on respiratory disease in adults; 3. Studies on cardiovascular disease in adults; 4. Studies on cancer incidence and mortality. ESCAPE responds to a specific FP7 call for a large collaborative project in the Environment and Health program. The call asks for research within existing cohorts among children as well as elderly adults as sensitive groups, and it asks to consider the role of other environmental exposures such as noise, and of biomarkers and gene-environment interactions. Whereas ESCAPE will focus, as requested, on air pollution and to a lesser extent traffic noise exposures, studies have been included which contain a wealth of data on other exposures (e.g., drinking water contaminants), on biomarkers and on genetics. ESCAPE will actively engage stakeholder organisations and policy makers so that results can be swiftly translated to support policy development and implementation.

Agency: Cordis | Branch: FP7 | Program: CP | Phase: ICT-2007.1.6 | Award Amount: 8.85M | Year: 2008

Experimentally driven research is key to success in todays Internet. Many test beds support research and development, and product prototyping in communication networks. However, they tend to specialise in particular access technologies or services, or explore near term product offerings, often with limited availability and openness. An open and sustainable large-scale shared experimental facility will allow European industry and academia to innovate today and to design the future Internet. The OneLab2 project will leverage the original OneLab projects PlanetLab Europe test bed and its international visibility to make this facility a reality.\n\nOneLab2 is built on three complementary pillars. The Platform Pillar will operate PlanetLab Europe, extending PlanetLab service across Europe, and federating with other PlanetLab infrastructures worldwide. It will integrate new features into the system. The Tools Pillar will enhance the test-bed-native network monitoring service that supports experiments. And the Customers Pillar will meet the needs of the facilitys customers by providing them with access to diverse facilities, achieved through federating different types of test bed. An experimental facility must know its customers. OneLab2 will do this by directly involving pilot customers who are testing novel ideas in networking research.\n\nOneLab2s coalition assembles some of the most highly respected networking research teams from university and industry labs in Europe. Each team has an active research agenda in new network technologies, network monitoring, or test bed management. OneLab2s success would mean that PlanetLab Europe is established as a competitive and federated facility with international visibility and a broad set of customers, implementing OneLab2s vision and research contributions. PlanetLab Europe will continue to function beyond the end of the project period, providing ongoing services to the research community at large.

Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2013.2.2.1-3 | Award Amount: 8.21M | Year: 2013

Conduct Disorder (CD) and Oppositional Defiant Disorder with symptoms of Conduct Disorder (which is included among the abbreviation CD throughout the proposal) has a highly negative impact for the affected individual as well as for families and society. Although the number of females exhibiting serious aggressive behaviours is growing, the majority of studies on aetiology and treatment of CD have focused on male subjects only, despite strong evidence for a differential neurobiological basis of female CD. The key aims of the FemNAT-CD consortium are to identify biomarkers and to study disease mechanisms from pre- to postpubertal female CD as well as new psychological and pharmacological treatment options for female adolescent CD targeting emotion processing abilities. With the present proposal, we aim at clarifying the phenomenology and neurobiology of female CD from pre-puberty to post-puberty. We will study the role of genetic and environmental risk factors on female CD, related psychopathology, brain structure and function, HPA axis and autonomic nervous system (ANS) disturbance to elicit CD specific endophenotypes and its biomarkers. We will describe the clinical, neuronal and neurocognitive phenotype of female CD from pre- to postpuberty and related neuroendocrine and ANS function as well as moderating, mediating and direct risk factors to identify distinct homogeneous subtypes to guide targeted future treatment approaches. We translate knowledge of neuropsychological and neurobiological characteristics into targeted intervention by performing a randomised controlled trial of an innovative 16-week DBT-CD-A psychological treatment program focussing on emotion processing. The effect oxytocin and serotonin on neural function underlying emotion processing and aggression will be studied in a female animal model and two proof of concept pharmaco-challenge studies. We also target several societal and education objectives. Our consortium brings together strong clinical and basic science expertise on paediatric CD, including a number of SMEs and a professional management company.

Agency: Cordis | Branch: FP7 | Program: CSA | Phase: ICT-2013.3.2 | Award Amount: 4.65M | Year: 2013

The aim of SSL-erate is to accelerate the uptake of high-quality SSL technology in Europe by means of open innovation with and by bringing validated information to all relevant stakeholders. A coordinated European effort is required to address the European societal challenges (in particular health & quality of life in an ageing society, energy consumption and resource efficiency), to resolve the specific challenges of the Lighting industry as noted in the results of the Green Paper Lighting the Future consultation (notably: poor SSL quality, lack of information and awareness among citizens) and to enable lighting solutions with a societal and environmental sustainability perspective, leading to a future in which Europe evolves to the global leadership in SSL systems and solutions. The lighting industry is highly fragmented. As a consequence of this the innovation speed and success rate have been too low and the benefits that we all expect from better lighting solutions, do not sufficiently materialize. To overcome this fragmentation, a collaborative way-of-working, using open-innovation and smart specialization principles, will be taken as the guiding approach. The active involvement of various stakeholders will be realized through workshops, but also through the creation of a web-based SSL-erate Innovation platform, which is planned to continue beyond the duration of this project. Relevant (lighting and non-lighting) companies, but also other stakeholders (like e.g. public authorities, property owners, research institutes, (lead) users/citizens, entrepreneurs, architects, installers) will become active contributors to this accelerated innovation process by applying validated insights on green business development and lighting effects on health & well-being in SSL business experiments.

Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: SEC-2012.7.2-1 | Award Amount: 2.00M | Year: 2013

Forensic analysis is an essential resource in the battle against organised crime and terrorist attacks. A key challenge in forensics is the detection of trace explosive residues at a post-blast scene or on the hands or clothes of an alleged suspect. Detection of the primer charge (e.g., PETN) is often hampered by higher-concentration residues from the main charge, e.g., ammonium nitrate. Detection of the primer can be essential in order to secure a prosecution, especially if the materials that comprise the main charge are commonly available, e.g., ammonium nitrate is present in fertiliser. ROSFENs goal is to deliver an advanced forensic platform for rapid, on-site direct detection and lab-quality analysis of narcotics, explosives and their precursors. The performance targets are detection limits down to 1 ng/mL, 1% false alarm rate and response time < 10 seconds. ROSFEN combines innovative technology from two leading SMEs: Microsaic Systems chip-based mass spectrometry and Environics ion filter systems. This novel platform removes the need for slow, costly chromatography methods currently used in lab-based analysis. ROSFEN will enable reduction of total analysis time (samples, blanks, controls) from hours to minutes, thus reducing the load on forensic labs and enabling intelligence-led investigations. ROSFEN will also innovate in the rapid analysis of new psychoactive drugs, by coupling the isomer selectivity of the ion filter technique with the detection sensitivity of tandem MS. ROSFEN will thus enable European industry to develop and deliver innovative technologies into key global markets: Analytical instruments for security applications ($2 billion annually) and the $3.3B market for mass spectrometry. The ROSFEN consortium comprises two research-intensive SMEs, two leading research groups and two end users. The end users have decades of expertise in forensic analysis of explosives and narcotics (FSNI), as well as crime scene analysis (PSNI).

Agency: Cordis | Branch: FP7 | Program: CSA-CA | Phase: ENV.2011.1.2.3-1 | Award Amount: 1.31M | Year: 2011

Today, human risk assessment and environmental risk assessment are typically separated. Existing risk assessment (RA) experience and regulations are challenged by future RA needs. - There is a lack of mutual understanding between subject matter experts of individual disciplines. - Data from toxicological and ecotoxicological studies is not readily accessible by risk assessors across disciplines. - The need for RA will continue to increase (e.g. REACH or toxicity of mixtures) along with budget restrictions and political and public pressure to reduce the number of animal tests. Therefore, more cost effective, predictive and rapid tests for high quality sustainable RA are needed including a better exploitation of existing data. - More transparency in RA is needed to allow better risk communication to regain consumer/public trust and to give unambiguous guidance for improved risk management. - Scientific RA plays an increasing role internationally for global risk governance and as a tool to support sustainable trade practices. Divergence often arises on risk policies and measures, sometimes due to different RA approaches. Therefore, stronger international co-operation in this area is needed. Against this background, the overall objective of the proposed coordination action HEROIC is to establish and co-ordinate a global network of European and international experts and stakeholders from different disciplines to establish stronger interfaces between human and environmental RA, between RA and risk management, between the various agencies and countries within the EU and between agencies and industry. To this end, the HEROIC consortium members will make full use of their own extensive networks to involve stakeholders and experts in workshops, roundtables and outreach activities. These coordinating activities will result in enhanced sharing of knowledge, building consensus and development of clear, easily understood, transparent and unambiguous integrated RA procedures.

Agency: Cordis | Branch: FP7 | Program: CP-CSA-Infra | Phase: INFRA-2010-1.1.32 | Award Amount: 11.03M | Year: 2010

ENSAR is the Integrating Activity of Nuclear Scientists from almost all European countries performing research in three of the major subfields of Nuclear Physics: Nuclear Structure, Nuclear Astrophysics and Applications of Nuclear Science. It proposes an optimised ensemble of Networking (NAs), Transnational Access and Joint Research Activities (JRAs), which will ensure qualitative and quantitative improvement of the access provided by the current seven infrastructures, which are at the core of this proposal. The novel and innovative developments that will be achieved by the RTD activities will also assure state-of-the-art technology needed for the new large-scale projects. Our community of nuclear scientists profits from the diverse range of world-class research infrastructures in Europe that can supply different ion beams and energies. We have made great efforts to make the most efficient use of these facilities by developing the most advanced and novel equipment needed to pursue their excellent scientific programmes and applying state-of-the-art developments in nuclear instrumentation to other research fields and to benefit humanity (e.g. archaeology, medical imaging). Together with multidisciplinary and application-oriented research at the facilities these activities ensure a high-level socioeconomic impact. To enhance the access to these facilities, the community has defined a number of JRAs, using as main criterion scientific and technical promise. These activities deal with novel and innovative technologies to improve the operation of the facilities. In addition, a key JRA aims at integrating the laboratories in Central and South-Eastern European countries with those elsewhere in Europe. The NAs of ENSAR have been set-up with specific actions to strengthen the communities coherence around certain research topics and to ensure a broad dissemination of results and stimulate multidisciplinary and application-oriented research at the Research Infrastructures.

Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH-2007-2.4.4-1 | Award Amount: 3.97M | Year: 2008

Autoimmune Addisons disease (AAD) is an endocrine disease resulting from the immune systems destruction of hormone producing cells in the adrenal cortex. Diagnosis is frequently first established after a life-threatening adrenal crisis, often resulting in untimely fatalities. The disease is rare, more common in women than in men, and also affects children. AAD very frequently occurs with other autoimmune diseases, such as type 1 diabetes mellitus, autoimmune thyroid disease and/or premature ovarian failure. Based on a European network of patient registry and biobanks, a translational approach using genetics, immunology, clinical management, and epidemiology, the project aims to unravel the pathogenesis and natural course of AAD, ultimately to improve diagnosis and treatment as well as to offer strategies for disease prevention. The consortium capitalises on the joint cutting edge expertise of leading European investigators covering all these fields. Exploiting these resources, we will describe the natural course of the disease with focus on factors limiting quality of life, and identify and characterise the disease-causing genes, using the corresponding disease in a spontaneous dog model and a gene targeted mouse model. In parallel, the cellular and molecular mechanisms of autoimmunity directed at the adrenal cortex will be unravelled both in humans with ADD and in the genetic mouse model. Together, these efforts will increase our still incomplete understanding of pathogenic pathways operational in AAD and pave the way for new therapies of this debilitating disorder. Moreover, clinical studies will be performed to evaluate more physiological and personalised treatment with cortisol also aimed at prevention. As an autoimmune model disease the results of the project will not only lead to the development of novel diagnostic and therapeutic interventions for Addison patients, but also increase our understanding of the pathogenesis of autoimmune diseases in general.

Agency: Cordis | Branch: FP7 | Program: ERC-CG | Phase: ERC-CG-2013-LS8 | Award Amount: 2.00M | Year: 2014

More than 150 years after the publication of Charles Darwins The Origin of Species, the identification of the processes that govern the emergence of novel species remains a fundamental problem to biology. Why is it that some groups have diversified in a seemingly explosive manner, while others have lingered unvaried over millions of years? What are the external factors and environmental conditions that promote organismal diversity? And what is the molecular basis of adaptation and diversification? A key to these and related questions is the comparative study of exceptionally diverse yet relatively recent species assemblages such as Darwins finches, the Caribbean anole lizards, or the hundreds of endemic species of cichlid fishes in the East African Great Lakes, which are at the center of this proposal. More specifically, I intend to conduct the so far most thorough examination of a large adaptive radiation, combining in-depth eco-morphological assessments and whole genome sequencing of all members of a cichlid species flock. To this end, I plan to (i) sequence the genomes and transcriptomes of several specimens of each cichlid species from Lake Tanganyika to examine genetic and transcriptional diversity; (ii) apply stable-isotope and stomach-content analyses in combination with underwater transplant experiments and transect surveys to quantitate feeding performances, habitat preferences and natural-history parameters; (iii) use X-ray computed tomography to study phenotypic variation in 3D; and (iv) examine fossils from existing and forthcoming drilling cores to implement a time line of diversification in a cichlid adaptive radiation. This project, thus, offers the unique opportunity to test recent theory- and data-based predictions on speciation and adaptive radiation within an entire biological system in this case the adaptive radiation of cichlid fishes in Lake Tanganyika.

Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: ENV.2011.1.2.2-2 | Award Amount: 4.58M | Year: 2011

Based on epidemiological evidence supporting an ssociation between residential exposure to extremely low frequency magnetic fields (ELF MF) and childhood leukaemia, ELF MF have been classified as possibly carcinogenic to humans. The proposed project aims to scrutinize the underlying biophysical mechanisms and to clarify a possible causal relationship between ELF MF exposure and cancer, especially childhood leukaemia. This will be achieved by 1) developing and applying novel experimental and computational techniques to close knowledge gaps in the exposure assessment to ELF MF and 2) applying advanced biological in vitro, ex vivo and in vivo models and techniques under well-defined exposure conditions to test likely interaction mechanisms. The selected experimental approach is based on epidemiological evidence and current knowledge about the molecular processes underlying acute leukaemia in children. It aims to investigate the possible impact of ELF-MF exposure: 1) on the epigenetic dynamics associated with hematopoietic cell lineage commitment and differentiation; epigenetic signatures will be monitored genome-wide, and mechanisms underlying eventual misprogramming will be addressed in gene promoter models; 2) on the alteration of signalling processes in cells; 3) on the induction of possible cytotoxic effects on CD8 positive T cells; and 4) on the genesis or evolution of childhood leukaemia by generating genetically modified advanced animal models. Advanced biophysical simulations with efficient numerical solvers combined with the latest tissue and cellular models will be implemented to support the bioexperiments. A risk assessment will be performed at the end based on studies conducted within the project and correlated to recent studies conducted outside the consortium by adapting and applying procedures as outlined by the International Agency for Research on Cancer (IARC) Monographs on the Evaluation of Carcinogenic Risks to Humans.

Agency: Cordis | Branch: H2020 | Program: RIA | Phase: PHC-17-2014 | Award Amount: 6.65M | Year: 2015

Most older adults have multiple chronic diseases (multimorbidity) and multiple medications (polypharmacy). However, multimorbid patients are often excluded from clinical trials and most guidelines address diseases in isolation. Inappropriate drug prescription and poor drug compliance are common and contribute to up to 30% of hospital admissions. OPERAM investigators developed STOPP/START criteria to detect inappropriate drug use, both over- and underuse. Applying these criteria limits unnecessary polypharmacy and reduces underuse of indicated medications, but it remains uncertain whether systematic pharmacotherapy optimisation can improve clinical outcomes and reduce costs.We propose a multicentre randomised controlled trial to assess the impact of a userfriendly software-assisted intervention to optimise pharmacotherapy and to enhance compliance in 1900 multimorbid patients aged 75 years. Outcomes will include drug-related hospital admissions, health care utilisation, quality of life, patient preferences and cost-effectiveness. We will also perform several network meta-analyses (NMA) to provide new comparative evidence on the most effective and safest pharmacological and non-pharmacological interventions to reduce common causes of preventable hospital admissions (e.g. falls, fractures, bleeding). Therapy optimisation in the multimorbid elderly, enhanced compliance and discontinuation of less effective interventions have the potential to improve clinical, quality of life and safety outcomes, while reducing costs. We will provide a structured method with practical software solutions for optimal prescribing and new comparative evidence from NMAs for addressing multimorbidity and polypharmacy by means of customised, patient-centred guidelines. OPERAM ultimately aims at better healthcare delivery in primary and hospital care, based on effective, safe, personalised and cost-effective interventions that can be applied to the rapidly growing older population in Europe.

Agency: Cordis | Branch: FP7 | Program: CP | Phase: ICT-2007.1.1 | Award Amount: 23.39M | Year: 2008

Todays network architectures are stifling innovation, restricting it mostly to the application level while the need for structural change is increasingly evident. The absence of adequate facilities to design, optimize and interoperate new networks currently forces a convergence to an architecture that is suboptimal for many applications and that cannot support innovations within itself, the Internet.\n4WARD overcomes this impasse through a set of radical architectural approaches built on our strong mobile and wireless background.. We improve our ability to design inter-operable and complementary families of network architectures. We enable the co-existence of multiple networks on common platforms through carrier-grade virtualization for networking resources. We enhance the utility of networks by making them self-managing. We increase their robustness and efficiency by leveraging diversity. Finally we improve application support by a new information-centric paradigm in place of the old host-centric approach. These solutions will embrace the full range of technologies, from fibre backbones to wireless and sensor networks.\nThe 4WARD results will allow new markets to appear, redefining business roles and creating new economic models. We will establish the Future Internet Forum as a leading standards body, enabling these new markets and opening them for old and new players alike, increasing opportunities for competition and cooperation and creating new products and services.\nThese goals can only be achieved by gathering a strong, industry-led consortium of the leading operators, vendors, SME, and research organisations, with the determination, skills, and critical mass to create cross-industry consensus and to drive standardisation. The project is designed for multiple phases; the first one will establish the core concepts and technologies and last for two years. The planned effort of about 2200 person months corresponds to the strategic importance of this endeavour.

Agency: Cordis | Branch: FP7 | Program: CP | Phase: ICT-2011.9.9 | Award Amount: 11.78M | Year: 2013

The overarching goal of our project is to develop systems based on direct and deterministic interactions between individual quantum entities, which by involving large-scale entanglement can outperform classical systems in a series of relevant applications.\nWe plan to achieve that by improving technologies from atomic, molecular and optical physics as well as from solid-state physics, and by developing new ones, including combinations across those different domains. We will explore a wide range of experimental platforms as enabling technologies: from cold collisions or Rydberg blockade in neutral atoms to electrostatic or spin interactions in charged systems like trapped ions and quantum dots; from photon-phonon interactions in nano-mechanics to photon-photon interactions in cavity quantum electrodynamics and to spin-photon interactions in diamond color centers.\nWe will work on two deeply interconnected lines to build experimentally working implementations of quantum simulators and of quantum interfaces. This will enable us to conceive and realize applications exploiting those devices for simulating important problems in other fields of physics, as well as for carrying out protocols outperforming classical communication and measurement systems.

News Article | November 10, 2015

A variety of ancient tetrapods—four-limbed ancestors of man, the other mammals, amphibians, and reptiles—could regenerate limbs and tails, says a startling paper in Nature. Among modern tetrapods, only salamanders fully regenerate limbs and tails. It was thought this was also true eons ago, as only salamanders grow digits front to back—while all other tetrapods grow them back to front. But Nature reported that, as far back as 300 million years ago, many different tetrapods—whether their digits formed backwards or forwards—fully regrew lost limbs. “The findings are surprising, and provide an important consideration when trying to understand genes specific to limb regeneration,” Australian Regenerative Medicine Institute regeneration expert James Godwin, Ph.D., told Bioscience Technology. The idea of regeneration as a lost ancient trait has been around “for some time. The news that regeneration predates stem [most primitive precursors of] salamanders provides critical evidence regenerative capacity was part of the original vertebrate blueprint, or acquired very early in vertebrate evolution. This paper is important. It extends our understanding of the evolutionary timeline of regeneration.” Godwin was uninvolved in the work. “A great surprise to see many early tetrapods capable of regenerating limbs and tails in a manner only salamanders do among extant tetrapods,” senior author, and visiting Brown University paleontologist Floria Witzmann, Ph.D., told Bioscience Technology. “We thought this was a derived characteristic in salamanders. Now it seems vice versa. Regeneration limb capacity appears a primitive characteristic of tetrapods only retained in salamanders. Other tetrapods –human beings – might possess the latent potential to regenerate limbs. This might lead to new approaches in regeneration research.” University of Basel vertebrate embryologist Rolf Zeller, Ph.D., told Bioscience Technology: “It is interesting the authors provide evidence, by analysis of fossil records, that in early tetrapods (distal) limb and tail regeneration appears more widespread than today.” Zeller, also uninvolved, cautioned limb regeneration has not yet been observed in fossil amniota (including human ancestors), just more distant fossil microsaurs. Others agreed, but consider microsaurs to be more closely related to amniota than to amphibians. And University of Padova evolutionary developmental biologist Alessandro Minelli, Ph.D., told Bioscience Technology the new study was “very important” for another reason: its proof fossil morphology (form) is key. “It shows that, in evolutionary developmental biology, morphology can be of no lesser value than molecular genetics,” said Minelli, also uninvolved. “Study of fossil ontogenies has revealed important features of evolution of development in vertebrates and trilobites, not to mention Cambrian larvae of invertebrates of problematic affinities. More is expected.” Alone among modern four-limbed vertebrates, salamanders regenerate hurt or missing limbs and tails their entire adult lives. As noted, it was thought the strange way they develop limbs was related to their regenerative skills. In other modern tetrapods digits form “post-axially,” back to front. Modern salamander digits form “pre-axially,” front to back. A team from Brown University, SUNY Oswego, and the Museum für Naturkunde, Berlin, looked for the link between regeneration and the salamander limb oddity in fossils of different Carboniferous and Permian (300-million-year old) amphibian groups from many natural history museums. Analyzed were a variety of individual amphibians at different developmental stages. Unexpectedly, the teams saw evidence of salamander-esque regenerative qualities in both ancient amphibians that developed digits like modern vertebrates, and ancient tetrapods that did not. First author Museum für Naturkunde paleontologist Nadia Froebisch, Ph.D., told Bioscience Technology: “We were surprised to find evidence for salamander-like regenerative capacities in tails and limbs in very distant lineages of Paleozoic tetrapod, some on the stem lineage to modern amphibians, but also in groups belonging to more distant relatives, and even in lepospondyl, which are more closely related to amniotes (that is, all fully terrestrial vertebrates, today represented by all birds, reptiles, and mammals). This indicates regenerative capacities are not special and derived for salamanders, but may be the primitive condition for all tetrapods.” Some of the evidence they found, she said: “Micromelerpeton [extinct European amphibian genus] shows a pattern and combination of abnormalities in the limbs characteristic for abnormalities in regenerated limbs of salamanders, differing from abnormalities associated with initial development.” More evidence, she said: Among microsaurs (aforementioned lepospondyls), they found specimens with asymmetries in limbs. “On one side, the limb is well-developed, and in accordance with the overall developmental stage of the individual. On the right side, the upper arm is equally well-developed, but more distal limb elements are much less well-developed, not fully ossified and differentiated, indicating a possible ongoing regeneration of the distal part.” Also among the specimens, the team saw that, “the tails in some microsaurs are very obviously regenerating: the well-developed vertebral column stops abruptly, and continues with small elements just differentiating. In salamanders, the primordial part of the new vertebral column in the tail is already subdivided on the cellular level, and these segments then give rise to new vertebral elements. This is also visible in microsaur specimens.” “There is no easy answer” why most tetrapods lost the skill, Froebisch said. “It seems counterintuitive something so seemingly useful as regenerating a limb should get lost. However, there could be good reasons, such as high energetic costs. Or another highly adaptive feature incompatible with regeneration was selected for, and regeneration got lost as a byproduct.” Salamanders are special in many ways, “including their metabolism, amazing plasticity in life history patterns, and in showing the largest cell sizes among extant vertebrates. It is also possible they are still regenerating because regeneration was never actively selected against (or for). So it is just still around.” “Astonishing” loss Witzmann told Bioscience Technology: “At first sight, it is astonishing a characteristic so obviously beneficial like limb regeneration was lost in most extant tetrapods. However, a number of hypotheses are summarized in a Bely and Nyberg review. Regeneration of limbs and other body parts are certainly energy intensive. In some cases, costs may be greater than advantages. Bely & Nyberg cite an example: for taxa with a short life-span, it might be more beneficial to spend more energy producing offspring, than regenerating body parts (which could take a long time).” Then there is the fact that adult frogs cannot regenerate limbs, but tadpoles can until metamorphic climax. Galis et al propose “the capacity of limb regeneration is timed to embryonic limb development. In amniotes, limbs are patterned during the phylotypic stage. Limbs develop relatively late in amphibians, after the phylotypic stage.” If it was adaptive for most tetrapods to lose regenerative talents, this could spell trouble for humans trying to revive them. But was it? “I don't think so,” Sorbonne Research Center on Paleobiodiversity and Paleoenvironments vertebrate paleontologist Michel Laurin, Ph.D., told Bioscience Technology. He was uninvolved with the new study. “It might be a by-product of other evolutionary constraints leading to adaptive characteristics outweighing the disadvantage of losing regenerative capacity.” Zeller noted that while “lizards drop tails, an advantage in escaping predators, this is apparently not the case for limbs. Maybe the potential to regenerate limbs was retained in few species due to evolutionary constraints, rather than a true and significant selective advantage.” Apparently, regeneration was not scotched to avoid cancer, as “salamander proteins have been shown to stop spreading cancer cells,” said Froebisch. “Fascinating system.” Laurin said a key step will be to check links “between developmental complexity and regenerative capacity. Even if we document the loss of regenerative capacity in amniotes, we will still never know why it happened if it is a singular event occurring on a branch (at the base of amniotes, or deeper in the tree) where other characteristics changed. How could we be sure to which of these regeneration loss is linked?” Another “big step,” said Zeller: determining “to what extent limb regeneration relies on the same molecular networks as tetrapod limb development, and to what extent gene regulatory networks governing regeneration are active during limb development in higher tetrapods.” Witzmann wants to investigate, on histological slides, “how bone injury healing proceeds on the tissue level in fossilized early tetrapods capable of limb and tail regeneration. It would be interesting to compare results with bone healing in extant amphibians.” Like Zeller, Minelli warned regeneration evidence is still wanting among amniotes. But he said the paper opens “a new vista on the evolutionary origin of the very peculiar pattern of digit formation only found in salamanders among living tetrapods. Parsimony applied to previously available evidence suggested this mode of digit formation was a specialization of salamander lineage. The newly added data suggest instead the mechanism was already present at least 80 million years before the origin of the salamander. Thus, the opposite polarity in digit formation, as found in all other living tetrapods, must have evolved secondarily in the frogs and – perhaps – amniotes (if this will depend on the condition at node two in the tree of figure 1, still unresolved).” Many questions remain, says Godwin. “It is clear all extant salamanders regenerate limbs, and the fossil record indicates this is a trait that goes back to early salamander ancestors. It is perhaps not too surprising preaxial limb development may have been present in Temnospondyli.” It is unclear if regeneration “is an acquired trait in some species (possibly through transposable elements acting as enhancers providing new functions), or if some species maintained regenerative abilities present in a common ancestor, and others lost these abilities at the expense of traits with higher selective pressure (e.g. the immune system). There is strong evidence on both sides of the ledger. It is likely a mixture of both, depending on tissue and injury context.” Limb and tail regeneration the same—or different? Limb regeneration, he added, “may rely on a limb-specific program. There is no guarantee tail regeneration uses exactly the same mechanism.” So a key next step, he said, is to precisely identify and quantify components acting as “roadblocks to human regeneration, while continuing the search for salamander-specific molecular pathways that could provide a blueprint for engineering human tissue regeneration. Humans are relatively fragile when it comes to tissue injury as adults. We have a lot to learn.” Godwin added salamanders regenerate in two different ways that humans also do—via stimulation of existing adult stem cells, and dedifferentiation of mature cells—if humans perform less dramatic feats. (For a look at recent developments in the understanding of natural human dedifferentiation in stomach, trachea, and kidney in response to stress, see earlier Bioscience Technology story.) “This is still an unresolved question that my students and I are working hard on,” Godwin told Bioscience Technology.  “Many different cell types are involved in salamander regeneration response of various tissue types.  In the heart, cardiomyocytes are replaced from existing cardiomyocytes with a transient down-regulation of mature cardiac genes [dedifferentiation of mature cells].” Godwin continued: “In the case of the limb, we still do not know the contribution of endogenous [native] stem cells in salamanders, but we do see that some cells dedifferentiate and express more embryonic gene markers.  Some multipotency is also observed.  This also in true in other contexts of salamander regeneration, such as the eye.  In limb muscle cells, it seems that in the newt the ratio is about 70 percent dedifferentiation, and about 30 percent pax7 satellite (muscle- restricted stem cells) from work done in Andras Simon's lab.  In a recent paper where Simon's lab joined with Elly Tanaka's lab, species differences between newts and axolotls were seen.  Axolotls replace their muscle in a mechanism like we do. So I think in a complex structure like the limb, the answer is likely to be: both.”

News Article | January 27, 2016

Conventional methods of stock monitoring are unsuitable for certain fish species. For example, the infestation of an area with invasive Ponto-Caspian gobies cannot be identified in time by standard methods. Researchers at the University of Basel have developed a simple, effective and cost-efficient test for these introduced non-native fish, they report in the magazine PLOS ONE. Gobies from the Black and Caspian Sea are spreading along the shipping routes in Central Europe and North America. They have been present in the Swiss part of the Rhine for about four years and already dominate the bottom of the stream in the region of Basel. So far, they have not advanced further than the water power plant in Rheinfelden, but a continuing expansion seems inevitable. Current methods of fish monitoring are not suited to adequately measure the spreading of Ponto-Caspian gobies as they are labor-intensive and not sufficiently sensitive. Accordingly, infestations of an area with gobies are often only discovered when they have reached high densities and efforts of containment remain futile. Researchers of the Department of Environmental Sciences of the University of Basel have now developed a test that allows for the detection of Ponto-Caspian gobies in streaming and stagnant water. With a commercially available, though slightly modified, water column sampler, water samples are taken from the bottom of the water body, where invasive gobies live. Via feces or scales, the fish release so-called environmental DNA into the stream. The water samples are then analyzed for traces of this so-called eDNA in the lab. The test developed at the University of Basel reacts exclusively to the genetic material of Ponto-Caspian gobies, but not to domestic fish species. The procedure is less time and cost-intensive than angling, and the samples can even be drawn by untrained individuals. Unlike electrofishing, the method does not impact the fish fauna and can consequently be used in protected zones and breeding grounds. Five species of invasive gobies populate wide areas of freshwater and brackish waters in Central Europe—the species that is most common to the region around Basel, Neogobius melanostomus, even figures among the 100 worst invaders in Europe. "Our test is one of the first approaches that targets a specific fish species and detects it successfully in flowing freshwater" says the study's lead author, Dr. Irene Adrian-Kalchhauser. "We hope that our work contributes to establishing eDNA as a standard method in European water resource management. Similar tests have been used for a few years to track the expansion of the Asian carp in the United States." Explore further: Invasive fish enters streams feeding Lake Michigan, but so far, so good

We humans walk with our feet. This is true, but not entirely. Walking, as part of locomotion, is a coordinated whole-body movement that involves both the arms and legs. Researchers at the Biozentrum of the University of Basel and the Friedrich Miescher Institute for Biomedical Research have identified different subpopulations of neurons in the spinal cord with long projections. Published in Neuron, the results show that these neurons coordinate movement of arms and legs and ensure a stable body posture during locomotion. The locomotor pattern consists of a highly controlled sequence of muscle contractions, which are controlled by neuronal circuits in the spinal cord and the brain. The research group of Prof. Silvia Arber at the Biozentrum of the University of Basel and the Friedrich Miescher Institute for Biomedical Research now reveal that specific, long projecting neurons, traversing our spinal cord, form an important basis for the coordination of fore- and hindlimbs. These neurons couple local networks over long distances and thereby ensure posture and rhythm of our body during locomotion. Even though humans rose from the quadrupedal position to stand on their feet during evolution, coordination and alternation patterns of the four limbs are still needed in order to move efficiently as in all other quadrupedal species. "We showed that the diametric movement of fore- and hindlimbs is reflected in neuronal circuits of the spinal cord", says Ludwig Ruder, first author of the study. Thus, axons of most excitatory neurons cross the midline of the spinal cord and contact contralateral networks. In contrast, inhibitory neurons project predominantly on the same side of the body. The diagonal and mirrored pattern of the excitatory neuronal connections is very interesting when observing the coordination of arms and legs in a runner as Usain Bolt. "During running, not only do his legs move, but synchronously and diametrically also his arms -- in complete coordination with each other", says Ruder. To demonstrate the importance of long projection neurons in the spinal cord for the walking pattern, the researchers selectively eliminated those neurons. "Upon inactivation of spinal long projection neurons that couple local networks, not only is the stability and speed during running impaired, but also the coordinated fore- and hindlimb movements fall apart at higher speeds", says Ruder. Interestingly, local movement patterns within a single limb remain however unaffected. This reinforces the specific role of long projecting neurons in the regulation of whole body movement. ... and distribute information of the brain In a next step, the research team observed that the neurons with long projections broadcast their signals throughout the spinal cord and receive extensive input from various brain regions. This organization of long projection neurons and their connections places them at an important intersection between integrating information from the brain and distributing it in the spinal cord. Up to now, researchers investigated mainly local spinal networks and their role in movement. In contrast, neurons with long projections have not been studied all that much. "However, the results of our new study show that long projecting neurons in the spinal cord exhibit a very important role for the coordination of the locomotor pattern", explains Silvia Arber. "Henceforth, we plan to investigate how the brain interacts differently with local and long projecting spinal neurons to control them specifically." In the long run, these results can be important to restore functionality after spinal cord injuries.

News Article | December 5, 2016

PARIS--(BUSINESS WIRE)--As we become more sedentary and better fed, the human race is faced with an epidemic of obesity and diseases such as type II diabetes. Although the correlation between body weight, food intake and exercise seems obvious, the regulatory mechanisms that link exercise, muscle biology, hormones and metabolism are not well understood. The focus of this year’s colloquium on Endocrinology hosted by the Fondation IPSEN is to gain an overview of the complexity of these pathways, to discuss the processes common to the various body systems involved and to identify possible therapeutic targets. Twelve international speakers will present their latest research at the meeting, which has been organised by Bruce Spiegelman (Dana Faber Cancer Institute and Harvard Medical School, Boston, USA) and the Fondation IPSEN (Paris, France). It will be held in Paris on December 5, 2016. The most obvious effects of exercise are on skeletal muscles, increasing muscle volume, strength and contractility. More importantly, exercise both maintains and increases the insulin sensitivity of muscle and affects the metabolism of the whole body by stimulating the uptake of glucose by muscles (Anna Krook, Karolinska Institutet, Stockholm, Sweden). A decrease in muscle insulin sensitivity is a big contributor to the onset of type II diabetes. The effectiveness of exercise regimes is modified by the availability of nutrients: the composition of the diet and the timing of meals in relation to exercise both alter the blood-borne signals that ultimately influence fuel metabolism and utilization (John Hawley, Mary Mackillop Institute for Health Research, Melbourne, Australia). Among these signals are the recently discovered hormones released by contracting muscles, now called myokines, such as the soluble peptide irisin. The role of steroid hormones in improving cardio-vascular fitness in response to exercise is being tested in population studies (Claude Bouchard, Pennington Biomedical Research Centre, Louisiana, USA). Metabolic stresses, such as low oxygen, ischaemia or glucose deprivation, stimulate the regulatory molecule AMP kinase, which acts as a cellular fuel gauge, providing an essential link between exercise, insulin signaling and the regulation of energy supplies. As well as its essential role in skeletal muscle, this molecule is pivotal in balancing the supply of nutrients to cells with the demand for energy throughout the body (Benoit Viollet, Institut Cochin-U1016 INSERM, Paris, France). Small RNA molecules known as micro-RNAs, which modulate the translation of DNA into proteins through their effect on messenger RNAs, also play a role in both skeletal muscle differentiation and in type II diabetes in response to exercise (Krook). Ultimately, energy production depends on the series of enzymatic reactions known as the citric acid cycle, which takes place in the mitochondria, the cell’s power generators. When the demand for energy goes up as a result of exercise, one pathway that coordinates the increase in size and number of mitochondria and optimizes the utilization of fuel requires the activation of the transcription factor EB (TFEB) (Marco Sandri, University of Padova, Padova, Italy). Muscles atrophy as a result of disuse, ageing and cachexia, the wasting experienced in terminal cancer. In rat muscles, the expression of genes involved in mitochondrial energy metabolism changes with ageing. The functional loss of muscle innervation seen in both ageing and cachexia is reflected in changes in genes responsible for the integrity of the neuro-muscular junction (David Glass, Novartis Institute for Biomedical Research, Cambridge, USA). In atrophying muscle, a set of genes is activated that produce muscle-specific enzymes responsible for labelling proteins for degradation in special organelles termed proteasomes (Alfred Goldberg, Harvard Medical School, Boston USA). Environmental stress activates compensatory mechanisms important for the maintenance of cell functions and their failure is a cause of cellular ageing, for example, the reduction in mitochondrial health that accompanies muscle atrophy. However, some of these effects can be ameliorated by exercise (Sandri). A pivotal molecule in mediating responses to external stimuli is PGC-1α, which regulates both the transcription of the genes involved in metabolism and the regulation of mitochondrial biogenesis. Increased activity of PGC-1α improves endurance, reduces fibre damage and muscle atrophy, and is important in determining muscle fibre type. PGC-1α may lie at the heart of improving the regenerative capacity of muscle through training: it activates both macrophages, which remove damaged muscle fibres, and the satellite cells that generate replacement fibres (Christoph Handschin, University of Basel, Basel, Switzerland). PGC-1 α is also important in another tissue central to energy regulation, the type of fat known as brown adipose tissue (BAT). This converts chemical energy into heat in a process known as thermogenesis, part of the body’s adaptive response to cold. Its presence in humans has been controversial but BAT is now recognized to form deposits deep in the neck and is found in some subcutaneous fatty tissue. It is distinct from white adipose tissue, the main form of fat deposited in the human body but it has recently been discovered that white fat can be converted to BAT through an intermediate ‘beige’ form (Francesco Celli, Virginia Commonwealth University, Richmond, USA). The hormonal signals that stimulate the conversion and the activation of beige and brown fats in response to cold, and how this increases the breakdown of post-prandial glucose, are being studied. The pathways through which these hormonal signals activate PGC1α and a second molecule found in BAT, termed UCP-1 (or thermogenin) may link exercise and thermogenesis: the hormone irisin produced by active skeletal muscle has been implicated stimulating the conversion of white to brown fat (Spiegelman). As well as its effects on muscle and fat body, exercise works in less obvious ways to keep the brain healthy. Problems with the breakdown of kynurenine, produced from the amino acid tryptophan and a precursor of enzymes involved in fat and carbohydrate metabolism, are implicated in several neuroinflammatory and psychiatric diseases, including stress and depression (Jorge Ruas, Karolinska Institutet, Stockholm, Sweden). During exercise, kynurenine is detoxified in skeletal muscle by conversion to kynurenic acid, which cannot cross the blood-brain barrier. This is yet another pathway involving PGC1α, a further example of the complexity of exercise-linked regulatory mechanisms. Yet another effect of exercise, at least in adult mouse brains, is to increase the birth of new neurons in the hippocampus, which helps to support learning and cognitive function. Irisin has a role here too: it increased the expression of the gene coding for the growth factor BDNF, essential for hippocampal neurogenesis (Christiane Wrann, Dana Faber Cancer Institute, Boston, USA). The research to be presented at the meeting will emphasise not only how important exercise is for maintaining a healthy metabolism but also the multiple ways in which it has its effects. Many of the results that will be discussed also provide leads for the development of therapeutics for use when exercise alone fails to have the desired effect or is inappropriate. Established in 1983 under the aegis of the Fondation de France, the ambition of the Fondation IPSEN is to initiate a reflection about the major scientific issues of the forthcoming years. The long-standing mission of the Fondation IPSEN is to contribute to the development and dissemination of scientific knowledge by fostering interaction between scientists and clinicians. It has developed an important international network of scientific experts who meet regularly at meetings known as Colloques Médecine et Recherche, dedicated to three main topics: neurosciences, endocrinology and cancer science. Moreover the Fondation IPSEN has started several series of meetings in partnership with the Salk Institute, the Karolinska Institute as well as with the science journals Cell and Science. The Fondation IPSEN produced several hundred publications and more than 250 scientists have been awarded prizes and grants.

Flash Physics is our daily pick of the latest need-to-know developments from the global physics community selected by Physics World's team of editors and reporters Extremely sensitive measurements of deformation and impact have been made using a sensor that is a combination of graphene and Silly Putty. Graphene is a layer of carbon just one-atom thick that has a number of very useful properties including high electrical conductivity. Silly Putty is a children's toy that is essentially a lump of a viscoelastic polysilicone material. When mixed together by researchers at Trinity College Dublin and the University of Manchester, the resulting "G-putty" is a good conductor of electricity. However, when the material is subject to even a tiny strain or impact, its electrical resistance increases sharply – before relaxing to its original value as the material "self-heals". This inspired Trinity's Jonathan Coleman and colleagues to make a sensor from G-putty that when mounted on the neck and chest of a subject could measure breathing pulse and blood pressure. The sensor was even able to detect the footsteps of a small spider. "The behaviour we found with G-putty has not been found in any other composite material," says Coleman, adding: "This unique discovery will open up major possibilities in sensor manufacturing worldwide". The material is described in Science. The International Linear Collider Collaboration (LCC), which promotes the planning and construction of a new linear collider to complement CERN's Large Hadron Collider (LHC), has appointed two new associate directors. Shinichiro Michizono of the Japanese particle-physics lab KEK will take over as associate director responsible for the International Linear Collider (ILC) design effort – taking over from Michael Harrison of Brookhaven National Laboratory in the US. James Brau of the University of Oregon will become associate director for physics and detectors for the LCC – replacing Hitoshi Yamamoto of Japan's Tohoku University. Both appointments will take effect in January 2017. The ILC and the Compact Linear Collider (CLIC) are currently the two most popular proposals for a next generation of linear colliders. If built, such a facility will smash together electrons and positrons to make very precise measurements of the Higgs particle and other phenomena that occur at collision energies of a few teraelectronvolts. Majorana fermions have been spotted at the end of an atomically thin iron wire by Ernst Meyer and colleagues at the Swiss Nanoscience Institute and the University of Basel. First hypothesized in 1937 by the Italian physicist Ettore Majorana, the fermions are their own antiparticles. While fundamental Majorana fermions have never been detected, they do exist as quasiparticles – collective excitations of electrons in some solids. Meyer and colleagues created their Majorana fermions by growing tiny iron wires (just one-atom thick and up to 70 nm long) on the surface of a superconductor. According to calculations by team members Jelena Klinovaja and Daniel Loss, a pair of Majorana fermions should exist in the nanowire – one at each end. Using scanning-tunnelling and atomic-force microscopes, the team was able to see clear evidence of the quasiparticles (see figure). Despite being separated by tens of nanometres, the Majoranas form a quantum state that can either be occupied or unoccupied by an electron. As such, the nanowire could form the basis of a robust quantum bit (or qubit) of information. The research is described in Quantum Information.

News Article | September 2, 2016

Organometallic catalysts are useful in lab research, and some are used industrially. They generally don’t work well in living cells. But researchers have now assembled an artificial enzyme with an organometallic active site in bacteria and coaxed it to catalyze an industrially relevant reaction that has never occurred before in live cells. They also used directed evolution, a lab mimic of natural evolution, to optimize and customize the catalyst in vivo. The work could lead to the use of living cells as molecular factories to produce high-value chemical products they would not normally make. Thomas Ward of the University of Basel, Sven Panke of the Swiss Federal Institute of Technology, Zurich, and coworkers carried out the study (Nature 2016, DOI: 10.1038/nature19114). The team’s aim was to create a synthetic metalloenzyme that could catalyze olefin metathesis—a Nobel Prize-honored reaction that rearranges carbon-carbon double bonds—in living cells. To accomplish this, the researchers engineered bacteria to express the protein streptavidin and transport it to the periplasm, the space between bacterial inner and outer membranes. Streptavidin has a deep pocket that binds the vitamin biotin. They attached biotin to a ruthenium-based organometallic compound that accelerates metathesis reactions. When the engineered bacteria are exposed to the biotin-based conjugate, they take it up into their periplasm. The conjugate then binds to streptavidin, turning it into an artificial enzyme with an olefin metathesis-catalyzing active site. The researchers performed directed evolution of the metalloenzyme in cells to improve its efficiency, change its substrate selectivity, and get it to produce different products. They use the periplasm because cellular components that inhibit metalloenzymes are present in only low concentrations there. The periplasm strategy was first used by F. Akif Tezcan’s group at the University of California, San Diego, to express a designed metalloprotein that catalyzed β-lactam hydrolysis in vivo (Science 2014, DOI: 10.1126/science.1259680). That artificial metalloenzyme self-assembled from native protein components and catalyzed a natural reaction. In contrast, the new metalloenzyme has a nonbiological component, the ruthenium compound, and catalyzes a nonnatural reaction, olefin metathesis. The study opens up the possibility of using nonbiological metal catalysts inside cells to benignly generate metabolites and signaling molecules that can be exploited to control cellular pathways, Tezcan comments. Directed evolution expert Frances Arnold of Caltech says, “I predict we will see an explosion of hybrid catalysts of this type. We’ve just scratched the surface of the new, genetically encoded catalysts we will be able to generate and then evolve in the lab to make highly active, selective, and useful synthetic enzymes.”

News Article | November 17, 2016

We humans walk with our feet. This is true, but not entirely. Walking, as part of locomotion, is a coordinated whole-body movement that involves both the arms and legs. Researchers at the Biozentrum of the University of Basel and the Friedrich Miescher Institute for Biomedical Research have identified different subpopulations of neurons in the spinal cord with long projections. Published in Neuron, the results show that these neurons coordinate movement of arms and legs and ensure a stable body posture during locomotion. The locomotor pattern consists of a highly controlled sequence of muscle contractions, which are controlled by neuronal circuits in the spinal cord and the brain. The research group of Prof. Silvia Arber at the Biozentrum of the University of Basel and the Friedrich Miescher Institute for Biomedical Research now reveal that specific, long projecting neurons, traversing our spinal cord, form an important basis for the coordination of fore- and hindlimbs. These neurons couple local networks over long distances and thereby ensure posture and rhythm of our body during locomotion. Even though humans rose from the quadrupedal position to stand on their feet during evolution, coordination and alternation patterns of the four limbs are still needed in order to move efficiently as in all other quadrupedal species. "We showed that the diametric movement of fore- and hindlimbs is reflected in neuronal circuits of the spinal cord," says Ludwig Ruder, first author of the study. Thus, axons of most excitatory neurons cross the midline of the spinal cord and contact contralateral networks. In contrast, inhibitory neurons project predominantly on the same side of the body. The diagonal and mirrored pattern of the excitatory neuronal connections is very interesting when observing the coordination of arms and legs in a runner as Usain Bolt. "During running, not only do his legs move, but synchronously and diametrically also his arms -- in complete coordination with each other," says Ruder. Long projecting neurons control whole body parameters of locomotion and distribute information of the brain To demonstrate the importance of long projection neurons in the spinal cord for the walking pattern, the researchers selectively eliminated those neurons. "Upon inactivation of spinal long projection neurons that couple local networks, not only is the stability and speed during running impaired, but also the coordinated fore- and hindlimb movements fall apart at higher speeds," says Ruder. Interestingly, local movement patterns within a single limb remain however unaffected. This reinforces the specific role of long projecting neurons in the regulation of whole body movement. In a next step, the research team observed that the neurons with long projections broadcast their signals throughout the spinal cord and receive extensive input from various brain regions. This organization of long projection neurons and their connections places them at an important intersection between integrating information from the brain and distributing it in the spinal cord. Up to now, researchers investigated mainly local spinal networks and their role in movement. In contrast, neurons with long projections have not been studied all that much. "However, the results of our new study show that long projecting neurons in the spinal cord exhibit a very important role for the coordination of the locomotor pattern," explains Silvia Arber. "Henceforth, we plan to investigate how the brain interacts differently with local and long projecting spinal neurons to control them specifically." In the long run, these results can be important to restore functionality after spinal cord injuries.

Doctor at Basel University Hospital honored for clinical work on management of non-vitamin K dependent oral anticoagulants in acute stroke patients LEVERKUSEN, 21-Feb-2017 — /EuropaWire/ — The third winner of the Bayer Thrombosis Research Award has been chosen. The Scientific Committee of the Bayer Science & Education Foundation has awarded the EUR 30,000 prize to Dr. David Seiffge from the stroke research group in the Department of Neurology at Basel University Hospital in recognition of his clinically significant work on the management and safety of non-vitamin K dependent oral anticoagulants (NOACs) in patients with acute stroke. Seiffge and the research group showed that stroke patients in everyday clinical practice can be treated with NOAC as little as five days after the acute event. The bleeding risk was low at just 1.3 percent per 100 patient-years. They also showed that in acute stroke patients the results of determining the plasma concentration of rivaroxaban are available after just 30 minutes, which could open up new options for acute therapy. An international pilot study initiated by Dr. Seiffge and Prof. Stefan Engelter showed, for example, that thrombolysis could be performed successfully in selected stroke patients who had been receiving NOAC therapy. The Thrombosis Research Award has honored aspiring up-and-coming researchers for outstanding achievements in the field of pure and clinical research into thrombosis since 2013. It was established in 2011 by the Bayer scientists Dr. Frank Misselwitz, Dr. Dagmar Kubitza and Dr. Elizabeth Perzborn, who won the German Future Prize in 2009 for developing the anticoagulant Xarelto®. “Advances in science, both at universities and research institutes and in industry, are society’s investment in the future. We want to boost research and promote excellence,” said Kemal Malik, member of the Bayer AG Board of Management responsible for Innovation and Chairman of the Foundation. “Bayer is working to discover and develop new treatment options for diseases for which there is a high level of medical need. It is therefore also very important for us to support pioneering achievements both in medical research and clinical application. In addition, through its foundations and particularly through the awarding of this prize, Bayer wants to increase appreciation for top-level research and medical progress,” continued Malik. It was these considerations that led the three Bayer researchers to donate the EUR 250,000 prize money for winning the German Future Prize to establish this award for up-and-coming researchers. Bayer doubled this initial funding to EUR 500,000. Said Dr. Frank Misselwitz, prize sponsor and Head of the Cardiovascular and Coagulation Therapeutic Area in Bayer’s Clinical Research, “David Seiffge is a talented clinician whose work stands out from that of the many other nominees. His work on the patient safety of non-vitamin K dependent oral anticoagulants delivers findings that are significant for clinical practice. In view of his outstanding scientific work, Dr. Seiffge is most particularly deserving of this award.” With the exception of the prize sponsors themselves, the scientific judging panel for the new award is made up exclusively of experts from universities and hospitals all over Germany: Professor Michael Böhm (Saarland University Hospital), Professor Christoph Bode (Freiburg-im-Breisgau University Hospital), Professor Andreas Greinacher (Ernst Moritz Arndt University Hospital, Greifswald), Professor Edelgard Lindhoff-Last (CCB – Cardiovascular Center Bethanien, Frankfurt-am-Main) and Professor Bernhard Nieswandt (Rudolph Virchow Center at the University of Würzburg). The prize is awarded by the Bayer Science & Education Foundation. The overriding aims of this foundation are to recognize outstanding research achievements, promote scientific talent and support key natural science projects in schools. In terms of content, the focus of its sponsorship activities is on natural sciences and medicine. Outstanding research achievements are honored by the Foundation in alternate years with the Hansen Family Prize and the Otto Bayer Prize, both of which are endowed with EUR 75,000. Two prizes for aspiring and up-and-coming researchers complete the program: the international Early Excellence in Science Award is presented annually in the categories biology, chemistry and medicine, each with prize money of EUR 10,000. The Bayer Thrombosis Research Award, presented every two years with prize money of EUR 30,000, supports scientists in German-speaking countries whose work focuses in particular on pure and clinical research into thrombosis. The 2017 prize winner, Dr. David Seiffge, studied medicine in Heidelberg, Rennes (France) and Basel. He investigated the effect of an artificial oxygen carrier in stroke-related hypoxic brain damage in an experimental doctoral thesis developed in Professor Lothar Schilling’s laboratory in Mannheim/Heidelberg. Dr. Seiffge has worked in the Department of Neurology at Basel University Hospital under Professor Ludwig Kappos since 2011. Most of his scientific work is done in the cerebrovascular research group under Professor Engelter and Professor Lyrer, focusing on clinical research into oral anticoagulants, stroke and cerebral hemorrhage. Special funding from the University of Basel is currently enabling Dr. Seiffge to study the clinical significance of plasma levels of non-vitamin K dependent oral anticoagulants. Bayer: Science For A Better Life Bayer is a global enterprise with core competencies in the Life Science fields of health care and agriculture. Its products and services are designed to benefit people and improve their quality of life. At the same time, the Group aims to create value through innovation, growth and high earning power. Bayer is committed to the principles of sustainable development and to its social and ethical responsibilities as a corporate citizen. In fiscal 2015, the Group employed around 117,000 people and had sales of EUR 46.3 billion. Capital expenditures amounted to EUR 2.6 billion, R&D expenses to EUR 4.3 billion. These figures include those for the high-tech polymers business, which was floated on the stock market as an independent company named Covestro on October 6, 2015. For more information, go to Forward-Looking Statements This release may contain forward-looking statements based on current assumptions and forecasts made by Bayer management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here. These factors include those discussed in Bayer’s public reports which are available on the Bayer website at The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments.

Hann D.R.,University of Basel | Gimenez-Ibanez S.,CSIC - National Center for Biotechnology | Rathjen J.P.,Australian National University
Current Opinion in Plant Biology | Year: 2010

The major virulence strategy for plant pathogenic bacteria is deployment of effector molecules within the host cytoplasm. Each bacterial strain possesses a set of 20-30 effectors which have overlapping activities, are functionally interchangeable, and diverge in composition between strains. Effectors target host molecules to suppress immunity. Two main strategies are apparent. Effectors that target host proteins seem to attack conserved structural domains but otherwise lack specificity. On the other hand, those that influence host gene transcription directly do so with extreme specificity. In both cases, examples are known where the host has exploited effector-target affinities to establish immune recognition of effectors. The molecular activity of each effector links virulence and immune outcomes. © 2010 Elsevier Ltd.

Jehle S.,University of Basel | Hulter H.N.,University of California at San Francisco | Krapf R.,University of Basel
Journal of Clinical Endocrinology and Metabolism | Year: 2013

Context: The acid load imposed by a modern diet may play an important role in the pathophysiology of osteoporosis. Objective: Our objective was to evaluate the skeletal efficacy and safety and the effect on fracture prediction of K-citrate to neutralize diet-induced acid loads. Design and Setting: We conducted a randomized, double-blind, placebo-controlled trial at a teaching hospital. Subjects: Subjects included 201 elderly (>65 yr old) healthy men and women (t-score of -0.6 at lumbar spine). Intervention: Intervention was 60 mEq of K-citrate daily or placebo by mouth. All subjects received calcium and vitamin D. Outcome Measures: The primary outcome was change in areal bone mineral density (aBMD) at the lumbar spine by dual-energy x-ray absorptiometry after 24 months. Secondary endpoints included changes in volumetric density and microarchitectural parameters by high-resolution peripheral quantitative computed tomography in both radii and both tibiae and fracture risk assessment by FRAX (Switzerland). Results: K-citrate increased aBMD at lumbar spine from baseline by 1.7 ± 1.5% [95% confidence interval (CI) = 1.0 -2.3, P < 0.001] net of placebo after 24 months. High-resolution peripheral quantitative computed tomography-measured trabecular densities increased at nondominant tibia (1.3 ± 1.3%, CI = 0.7-1.9, P < 0.001) and nondominant radius (2.0 ± 2.0%, CI = 1.4 -2.7, P < 0.001). At nondominant radius, trabecular bone volume/tissue volume increased by 0.9 ± 0.8%, (CI = 0.1-1.7), trabecular thickness by 1.5 ± 1.6% (CI = 0.7-2.3), and trabecular number by 1.9 ± 1.8% (CI = 0.7-3.1, for all, P < 0.05). K-citrate diminished fracture prediction score by FRAX significantly in both sexes. Conclusions: Among a group of healthy elderly persons without osteoporosis, treatment with K-citrate for 24 months resulted in a significant increase in aBMD and volumetric BMD at several sites tested, while also improving bone microarchitecture. Based on the effect on fracture prediction, an effect on future fractures by K-citrate is possible. Copyright © 2013 by The Endocrine Society.

Ledermann T.,University of Basel | Kenny D.A.,University of Connecticut
Journal of Family Psychology | Year: 2012

Studying dyads, very often there is a theoretical construct that has an effect on both members, such as relationship harmony or shared environment. To model such influences, the common fate model (CFM) is often the most appropriate approach. In this article, we address conceptual and statistical issues in the use of the standard CFM and present a series of variations, all of which are estimated by structural equation modeling (SEM). For indistinguishable dyad members (e.g., gay couples), we describe the use of a multilevel SEM method. Throughout the paper, we draw connections to the actor-partner interdependence model (APIM). We also discuss the analysis of hybrid models that combines both the CFM and the APIM. The models are illustrated using data from heterosexual couples. © 2011 American Psychological Association.

Borgwardt S.,University of Basel | Borgwardt S.,King's College London | Fusar-Poli P.,King's College London
British Journal of Psychiatry | Year: 2012

Psychiatric imaging needs to move away from simple investigations of the neurobiology underlying the early phases of schizophrenia to translate imaging findings in the clinical field, targeting clinical outcomes including transition, remission and response to preventive interventions.

Loss D.,University of Basel | Pedrocchi F.L.,University of Basel | Leggett A.J.,University of Illinois at Urbana - Champaign
Physical Review Letters | Year: 2011

We extend the Mermin-Wagner theorem to a system of lattice spins which are spin coupled to itinerant and interacting charge carriers. We use the Bogoliubov inequality to rigorously prove that neither (anti-) ferromagnetic nor helical long-range order is possible in one and two dimensions at any finite temperature. Our proof applies to a wide class of models including any form of electron-electron and single-electron interactions that are independent of spin. In the presence of Rashba or Dresselhaus spin-orbit interactions (SOI) magnetic order is not excluded and intimately connected to equilibrium spin currents. However, in the special case when Rashba and Dresselhaus SOIs are tuned to be equal, magnetic order is excluded again. This opens up a new possibility to control magnetism electrically. © 2011 American Physical Society.

Gangadharaiah S.,University of Basel | Braunecker B.,University of Basel | Simon P.,University Paris - Sud | Loss D.,University of Basel
Physical Review Letters | Year: 2011

We show that one-dimensional electron systems in the proximity of a superconductor that support Majorana edge states are extremely susceptible to electron-electron interactions. Strong interactions generically destroy the induced superconducting gap that stabilizes the Majorana edge states. For weak interactions, the renormalization of the gap is nonuniversal and allows for a regime in which the Majorana edge states persist. We present strategies of how this regime can be reached. © 2011 American Physical Society.

Klan P.,Masaryk University | Solomek T.,Masaryk University | Bochet C.G.,University of Fribourg | Blanc A.,CNRS Institute of Chemistry | And 5 more authors.
Chemical Reviews | Year: 2013

Photoremovable protecting groups (PPGs) provide spatial and temporal control over the release of various chemicals such as bioagents. Nitrobenzyl, nitrophenethyl compounds, and their dimethoxy derivatives (nitroveratryl) are by far the most commonly used PPGs. They are synthetically malleable and accessible, offering a wide range of structures for designed applications. They offer excellent spatial and temporal control for the substrate release. Their applications span many scientific fields, from DNA chip technology, drug delivery, and photoregulation of proteins, to rheology, solid-phase synthesis, surface chemistry, and nanotechnology. Multiphoton excitation can provide superior spatial resolution, and the new chromophores included offer more precise temporal control for addressing the dynamics of in-vivo events in living organisms. The diversity of different PPGs, operating by different mechanisms and bearing different types of chromophores, opens the door for wavelength-selective deprotection.

Agency: Cordis | Branch: H2020 | Program: RIA | Phase: YOUNG-1-2014 | Award Amount: 2.92M | Year: 2015

Through an innovative use of four key concepts (resilience, capability, active agency and negotiation) and primary data (life course interviews, vignette experiments), NEGOTIATE will deliver gender-sensitive comparative knowledge about consequences of early job insecurity. We move beyond the state-of-the-art by investigating the linkages across macro, meso and micro levels as mechanisms of early job insecurity. General labour market processes and a severe employment crisis currently define the macro level. The micro level is characterised by young people with unequal opportunities to influence individual job prospects. The organisation of meso level structures creates differential access to public and private support within and across countries. NEGOTIATEs core question is how young peoples scope for agency interacts with different layers of structural conditions in a multi-level governance system. By actively involving national and European stakeholders including young people NEGOTIATE will contribute to policies that promote the employability of young Europeans, thus maximising societal and scientific impact. We will observe the present, learn from the past and project the future to inform policies that help prevent early labour market exclusion and adverse effects of job insecurity in the short and long term, thereby leading Europe closer to the Europe 2020 goals. A trans-disciplinary Consortium of nine research institutions from BG, CZ, DE, EL, NO, PL, ES, CH, UK and one international CSO will implement NEGOTIATE. The participating countries are differently affected by the economic crisis and display historical variations across key institutional factors, such as welfare state arrangements, employment relations and youth transition regimes. The participation of SOLIDAR will strengthen NEGOTIATEs policy impact. Overall, the participants wide set of research skills enable a rich combination of advanced quantitative and qualitative comparative analyses.

Agency: Cordis | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-2013-ITN | Award Amount: 3.99M | Year: 2014

The MOLESCO network will create a unique training and research environment to develop a pool of young researchers capable of achieving breakthroughs aimed at realising the immense potential of molecular electronics. In part this will involve the major challenges of design and fabrication of molecular-scale devices. To deliver this step-change in capability, MOLESCO will coordinate the activities of internationally-leading scientists from six different countries. MOLESCO has secured the participation of nine private sector partners, including one of Europes leading industrial electronics-research laboratories (IBM ResearchZurich) as a full partner. A highly-integrated approach to the experimental and theoretical aspects of molecular-scale electronics will deliver the fundamental knowledge and new fabrication strategies needed to underpin future nanotechnologies targeted for electronics applications. MOLESCO represents a highly interdisciplinary and intersectoral collaboration between teams with an extensive portfolio of skills, including molecular synthesis, fabrication of molecular junctions, imaging of molecular junctions with atomic resolution, measurements of charge transport, and electronic structure and transport calculations. Training will be delivered in a series of high-priority actions primarily aimed at providing the researchers with an outstanding career development platform. The network has a strong focus on interdisciplinary training; it is built on several well-established and fruitful collaborations between the partners and seeks to bridge an existing educational gap in the European Research Arena. The development of complementary skills (presentation, management, technology transfer, IP protection, outreach and intersectoral training) will be implemented throughout the lifetime of the project. Specialist professional training in dissemination and outreach will be delivered by our Associate Partner BLP, a professional media production company.

Agency: Cordis | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-2011-ITN | Award Amount: 4.00M | Year: 2012

This network brings together an exceptionally strong group of world leading experts in nano-science and technology in order to achieve breakthroughs in understanding and successful utilisation of nanoscale systems in future devices. The focus of the consortium is on few spin nano-systems in solid-state materials including III-V semiconductors and Carbon-based structures: carbon nano-tubes, graphene and diamonds. Such wide material base emphasizes the truly intersectoral character of this collaboration opening opportunities for crossing the boundaries between several areas of solid-state physics and technology. In order to ensure the highest impact of this collaboration in the emerging supra-disciplinary field of physics and applications of spin nano-systems, we bring together the expertise of the world top class research institutions and industry from 4 European countries. The network will deliver top international level multidisciplinary training to 11 early stage researchers and 5 experienced researchers, offering them, in particular, an extended program of multinational exchanges and secondments. The research and development under this network will undertake a broad scope of tasks important for implementation of spin nano-systems in future devices, such as non-volatile ultra-compact memories, nano-magnetometers, spin qubits for quantum information, and high-efficiency single photon sources. The objectives of the network include: (1) Realization and optical control of coherent single spins in nanostructures; (2) Spin-orbit interaction and spin-orbit qubits in nanostructures; (3) Advanced techniques for manipulation of nuclear spins on the nanoscale; (4) Generation of long-distance entanglement between single spins.

Agency: Cordis | Branch: FP7 | Program: CP | Phase: ICT-2013.9.7 | Award Amount: 8.27M | Year: 2013

The DIADEMS project aims at exploiting the unique physical properties of NV color centres in ultrapure single-crystal CVD-grown diamond to develop innovative devices with unprecedented performances for ICT applications. By exploiting the atom-like structure of the NV that exhibits spin dependent optical transitions, DIADEMS will make optics-based magnetometry possible.\nThe objectives of DIADEMS are to develop\n- Wide field magnetic imagers with 1 nT sensivities,\n- Scanning probe magnetometer with sensitivity 10 nT and spatial resolution 10 nm,\n- Sensor heads with resolution 1 pT.\n\nTo reach such performances, DIADEMS will:\n- Use new theoretical protocols for sensing,\n- Develop ultrahigh purity diamond material with controlled single nitrogen implantation with a precision better than 5 nm,\n- Process scanning probe tips with diametre in the 20 nm range,\n- Transfer them to AFM cantilever, improve the emission properties of NV by coupling them with photonic cavities and photonic waveguides.\n\nDIADEMS outputs will demonstrate new ICT functionalities that will boost applications with high impact on society:\n- Calibration and optimization of write/read magnetic heads for future high capacity (3 Tbit per square inch) storage disk required for intense computing,\n- Imaging of electron-spin in graphene and carbon nanotubes for next generation of electronic components based on spintronics,\n- Non-invasive investigation of living neuronal networks to understand brain function,\n- Demonstration of magnetic resonance imaging of single spins allowing single protein imaging for medical research.\n\nDIADEMS aims at integrating the efforts of the European Community on NV centres to push further the limits of this promising technology and to keep Europes prominent position.

Agency: Cordis | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-ITN-2008 | Award Amount: 4.37M | Year: 2009

The objective of BIOTRAINS is to deliver a trans-European network of industrially oriented white biotechnologists fully trained in the application of biocatalysis to sustainable chemical manufacturing. Their skills will be developed through a joint research programme at leading national CoEs (Centre of Excellence) with research projects identified by internationally leading Principal Investigators in this field. There is an urgent need for these scientists to support the KBBE (Knowledge Based BioEconomy) identified by the SUSCHEM (The European Technology Platform for Sustainable Chemistry) technology platform and they will provide the key to the European future that has defined the work programme for FP7 in this field. We present a doctoral training program where the scientific research is integrated with industrial training, supervised by key academic and industrial scientists from all the disciplines needed to deliver industrial relevant science. The UK Centre of Excellence in Biocatalysis (CoEBio3) will manage the project to ensure that the collaboration is integrated seamlessly across both academic and industrial centres, and across geographical boundaries. Most importantly, CoEBio3 will manage efficient technology transfer between the academic scientists and industry. This will ensure a state-of-the-art programme meeting current industry needs in both people and technology. A structured exchange programme with both industrial placements and CoE exchanges will ensure that national leading-edge skills together with specialist equipment training are transferred across Europe, and will define best practice for both academia and industry.

Agency: Cordis | Branch: FP7 | Program: CP | Phase: ICT-2009.8.2 | Award Amount: 7.14M | Year: 2010

The SOLID concept is to develop small solid-state hybrid systems capable of performing elementary processing and communication of quantum information. This involves design, fabrication and investigation of combinations of qubits, oscillators, cavities, and transmission lines, creating hybrid devices interfacing different types of qubits for quantum data storage, qubit interconversion, and communication. The SOLID main idea is to implement small solid-state pure and hybrid QIP systems on common platforms based on fixed or tunable microwave cavities and optical nanophotonic cavities. Various types of solid-state qubits will be connected to these hubs: Josephson junction circuits, quantum dots and NV centres in diamond. The approach can immediately be extended to connecting different types of solid-state qubits in hybrid devices, opening up new avenues for processing, storage and communication. The SOLID objectives are to design, fabricate, characterise, combine, and operate solid-state quantum-coherent registers with 3-8 qubits. Major SOLID challenges involve: Scalability of quantum registers; Implementation and scalability of hybrid devices; Design and implementation of quantum interfaces; Control of quantum states; High-fidelity readout of quantum information; Implementation of algorithms and protocols. The SOLID software goal is to achieve maximal use of the available hardware for universal gate operation, control of multi-qubit entanglement, benchmark algorithms and protocols, implementation of teleportation and elementary error correction, and testing of elementary control via quantum feedback. An important SOLID goal is also to create opportunities for application-oriented research through the increased reliability, scalability and interconnection of components. The SOLID applied objectives are to develop the solid-state core-technologies: Microwave engineering; Photonics; Materials science; Control of the dynamics of small, entangled quantum systems

Agency: Cordis | Branch: FP7 | Program: CP | Phase: ICT-2009.8.7 | Award Amount: 3.48M | Year: 2011

Information technology is partly based on magnetism (memory) and partly on electricity (processors). Increasing control over individual electron charges and spins provides new device functionality. For both charges and spins, molecular devices provide ideal test beds, which have witnessed increased interest over the last decade but the understanding and control of which is still in an infant state. The aim of ELFOS is to take single-molecule electronics to the next level in which single molecule device functionality will be exploited. We will combine different experimental test beds to gain knowledge about molecular functionality with an emphasis on the spin degrees of freedom and how to exploit these in device configurations using electric fields. In information processing, spins have the general advantage over charges in that they are less sensitive to the coupling between the molecule and its environment and hence to the molecular orientation which is difficult to control at the atomic level. Furthermore, the control of molecular spins by electric fields is preferable over magnetic-field or light-driven control since it allows for the application of strong fields at a local scale and for the fast manipulation of spin states. Guided by theoretical studies of radically new concepts, we will manipulate the molecular spin either by controlling the charge states of the molecule by the gate or by the gate directly. The molecules of interest are single-molecule magnets, spin triangles, spin chains and spin-crossover compounds. The experiments should provide an answer to key questions such as: Can individual magnetic molecules be addressed electrically as bits or qubits? and How can they be used as switches? Applied aspects are long term with high risk and high potential for applications.

Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH-2009-2.4.4-1 | Award Amount: 7.77M | Year: 2009

Myasthenia Gravis (MG) is a heterogeneous rare autoimmune neurological disease affecting the neuromuscular junction (NMJ). The molecular events causing and maintaining MG are still unknown and current treatments do not lead to remission and entail considerable side-effects stressing the need for improved therapies. We will address the: 1. Natural course of disease: determine factors associated with disease onset and/or affecting the course of disease and patients quality of life in subgroups of MG patients including children, twins, females and elderly patients. 2. Etiology of MG: identify new genetic, epigenetic and environmental risk factors and investigate immunological key molecules associated with MG onset. 3. Pathogenic mechanisms at the NMJ: a) study molecular changes in the NMJ by proteomic, genetic, epigenetic and microRNA analyses in MG patients and experimental models; b) analyze morphological changes at the NMJ in mouse models expressing YFP nerves and mice transgenic for mini-agrin; c) evaluate the capacity of muscle cell satellites from MG patients to regenerate muscle and form new endplates in immunodeficient mice. 4. New diagnostic and monitoring assays: a) identify pathogenic and protective factors in MG sera; b) improve the sensitivity of current assays; c) Identify new biomarkers associated with different MG subgroups by proteomic and microRNA analyses; d) Identify patients response to treatment and liability to side effects by pharmacogenomic analyses. 5. Novel therapies: a) study new cell-based therapies aimed at regulating the autoimmune response by regulatory T cells or mesenchymal stem cells in humanized mice; b) immunoadsorb pathogenic antibodies; c) test non-cell based immmunomodulatory therapies; d) target epigenetic regulators. This multidisciplinary project linking basic researchers with clinical neurologists, SMEs and several European patient associations should favor a translational approach for improved MG management

Agency: Cordis | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2015-ETN | Award Amount: 3.97M | Year: 2016

This network brings together world-leading experts in nano-science and technology from 6 European countries in order to achieve breakthroughs in understanding and successful utilization of nanoscale solid-state spin systems in emerging quantum technologies. The proposed innovative science in the supra-disciplinary field of physics and applications of spin nano-systems will underpin breakthrough developments in quantum computing, quantum communications and networks, and nano-imaging. Important innovative step consolidating the joint effort of the whole consortium is the focus on crystalline solids where magnetic interactions of electron spins with lattice nuclei are negligible and well-controlled. We will develop electrically-controlled spin-quantum-bits (qubits) in Si-Ge quantum dots and nanowires; will optically manipulate spin impurities in diamond in applications for quantum computing and networks and in nano-magnetometry; will achieve new understanding of quantum phenomena due to the spin-valley coupling in atomically thin 2D semiconductors, an emerging class of materials with a promise for quantum technologies. Research training to 15 early stage researchers will be delivered by 14 academic and 7 industrial groups. Network-wide training course in transferable skills will be specially developed and delivered by the Think Ahead (Sheffield), an award winning initiative at the University of Sheffield (award by the Times Higher Education, 2014). Current proposal is designed to advance this multi-disciplinary research field significantly beyond the state-of-the-art, and train a new cohort of researchers capable of developing spin-based solid-state quantum technologies towards real-life applications in the next 5 to 10 years.

Agency: Cordis | Branch: FP7 | Program: CP-FP-SICA | Phase: HEALTH-2009-4.3.3-1 | Award Amount: 5.68M | Year: 2009

The subject of the proposal is the search and analysis of genomic variations underlying Alzheimers disease (AD), alcoholism and schizophrenia wide-spread diseases in human populations. Schizophrenia and alcoholism are common forms of behavior pathology and disability in adult life. AD is a most common form of dementia in human populations. Though the genomic variations presumably associated with AD, alcoholism and schizophrenia were described in preliminary studies for European populations, the significance of the putatively associated alleles, genetic background as well as the role of environmental factors is still poorly understood for them. Within the framework of this project we plan to extend the studies of genomic variations underlying these diseases by performing genome-wide association analysis in cohorts of patients and normal individuals from several ethnic populations of Europe and Russia.The genetic factors for cognition endophenotype will also be studied. Candidate regions, both newly found and reported previously for these diseases will be additionally analyzed by sequencing. Such large scale population studies combined with deep analysis of particular genes and genomic regions will allow us to reveal genetic reasons for susceptibility to these diseases. On the basis of this research we propose to contribute to development of a diagnostic instrument for the analysis of genetic risk factors for AD, alcoholism and schizophrenia. Comparison of several ethnic cohorts (different populations from Russia and Central/Western and Southern Europe) will also help to elucidate the influence of genetic background and environmental factors on the etiology of neuropsychiatric diseases. Consortium includes 6 groups from EU/AC and 7 groups from Russia. The participants are leading specialists in their fields and have joint publications on subjects related to this proposal.

Agency: Cordis | Branch: H2020 | Program: RIA | Phase: COMPET-4-2016 | Award Amount: 3.77M | Year: 2016

European Robotic goal-oriented autonomous COntroller (ERGO) The specific objective of ERGO is thaen to deliver the most advanced but flexible space autonomous framework/system suitable for single and/or collaborative space robotic means/missions (orbital and surface rovers) demanding robust operations with adaptable levels of autonomy. Due to the intrinsic similarities of addressed scenarios, especially for what concerns surface applications, ERGO has to be/and has been thought so to be applicable to terrestrial robotic applications requiring high level of autonomy. In order to achieve this challenging objective, the ERGO team has been settled such to guarantee strong background both in robotics in general and operational autonomous space robotic missions (GMV, ADS, SciSys), as well as state of the art expertise in goal oriented autonomy (GMV), planning (King College, University of Basel, GMV), guidance and navigation for robotic applications (GMV, ADS, SciSys), formal validation and verification (UGA-UGA), on-board critical software design and development (GMV, Ellidiss).

Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: HEALTH-2009-2.2.1-2 | Award Amount: 15.03M | Year: 2010

The aim of EU-GEI is to identify the interactive genetic, clinical and environmental determinants involved in the development, severity and outcome of schizophrenia (EU-GEI, Schiz. Res. 2008; 102: 21-6). In order to identify these interactive determinants, EU-GEI will employ family-based, multidisciplinary research paradigms, which allow for the efficient assessment of gene-environment interactions. In order to go beyond old findings from historical convenience cohorts with crude measures of environmental factors and clinical outcomes, the focus in EU-GEI will be on recruitment of new, family-based clinical samples with state-of-the-art assessments of environmental, clinical and genetic determinants as well as their underlying neural and behavioural mechanisms. New statistical tools will be developed to combine the latest multilevel epidemiological with the latest genome-wide genetic approaches to analysis. Translation of results to clinical practice will be facilitated by additional experimental research and risk assessment bioinformatics approaches. This will result in the identification of modifiable biological and cognitive mechanisms underlying gene-environment interactions and the construction of Risk Assessment Charts and Momentary Assessment Technology tools which can be used for (i) early prediction of transition to psychotic disorder in help-seeking individuals with an at-risk mental state and (ii) early prediction of course and outcome after illness onset. In order to reach these goals, EU-GEI has assembled a multidisciplinary team of top schizophrenia researchers who have the range of skills required to deliver a program of research that meets all the calls requirements and who have access to / will collect a number of unique European samples. The partners in EU-GEI represent the nationally funded schizophrenia / mental health networks of the UK, Netherlands, France, Spain, Turkey and Germany as well as other partners.

Agency: Cordis | Branch: FP7 | Program: MC-ITN | Phase: PEOPLE-2007-1-1-ITN | Award Amount: 2.80M | Year: 2008

The FUNMOLS network will tackle major challenges in the field of molecular electronics. Ten internationally-leading European research groups from five different countries [including one of Europes leading industrial electronics-research groups (IBM Zurich)] have joined forces as full participants, combining expertise in synthetic chemistry, nanoscale physics and device engineering, surface electrochemistry and electronic structure calculations. Our highly-integrated approach involves a convergence of experiments including syntheses and theory in electron transport through single molecules, which will represent a major step towards the realisation of future scalable molecular electronics technologies and processes. In the longer term, the insights gained will contribute to the fabrication of functional nanoscopic architectures and their integration into a higher hierarchical level. System parameters like electric field, light, temperature or chemical reactivity are envisaged as possible triggers of future nanoelectronic devices. This European consortium is committed to promote breakthroughs at the frontier of science. The training dimension of the FUNMOLS network is reflected in the high priority we will give to a series of actions specifically aimed at early stage researchers (ESRs). These include: education and knowledge dissemination through the organisation of Workshops, Tutorial Courses, Annual Network Meetings, Training Schools, International Conferences and Mobility Programmes. The network as a whole builds on several fruitful collaborations between the PIs and seeks to close an existing educational gap in the European Research Arena. The development of complementary skills (presentation, management, technology transfer, IP protection) will be implemented actively throughout the lifetime of the project. A constant interaction beyond those involved primarily in research will provide the wider scientific community with information on our new technology.

Agency: Cordis | Branch: FP7 | Program: CP | Phase: ICT-2009.8.0 | Award Amount: 3.26M | Year: 2011

SE2ND is a joint experimental and theoretical effort. SE2ND strives to develop a highly efficient and continuous solid-state source of spatially separated spin-entangled electrons. A source of this kind, integrated with other electronic elements, will be of great importance in future quantum processors, where they provide, for example, entanglement distribution required to synchronize quantum circuits, and enable secure communication. The project will exploit entangled electron pairs that naturally occur in the ground state of a superconductor. The key target device of SE2ND is an electron-pair splitter with two defining key functions: 1) it ensures that pairs are emitted one by one, and 2) the two electrons of the pair are spatially separated by directing them into two different output channels, while maintaining their entanglement. Both objectives can be realized in carefully tuned double quantum dots. Hybrid double quantum dots will be realized in high-quality low-dimensional materials (semiconducting nanowires, carbon nanotubes and graphene) and integrated together with superconducting injectors, serving as sources of the electron pairs, ferromagnetic elements and microwave cavities in order to assess the degree of pair splitting and electron entanglement. SE2ND will explore the relevant material and fabrication parameters, optimize the splitting efficiency, assess the spin relaxation rate, coherence and the degree of entanglement to provide an optimized source with near to unity efficiency. SE2ND will extensively develop hybrid nanodevices which exploit the unique properties of quantum dots in proximity to superconductors and ferromagnetic materials, thereby providing a novel toolbox for electron-based quantum information technology, helping to maintain Europe at the forefront of this rapidly evolving field.

Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: KBBE-2009-3-1-04 | Award Amount: 4.27M | Year: 2010

The consortium will discover and carry to the stage of development candidates, plant derived small molecules with potential as new cosmetic and agrochemical agents. These compounds will derive from plants originating from major biodiversity hotspots in Europe, Africa, Latin America, and the Asia-Pacific region. The starting point of the project will be a diversity-oriented natural product library of 500 compounds from the existing compound repositories of three project partners. Screening of this compound library in assay panels for agrochemical (antifungal, herbicidal, insecticidal) and cosmetic properties (UV-protection, anti-aging, anti-hyperpigmentation) will rapidly identify promising scaffolds. This knowledge will serve as entry points for a chemotaxonomy and chemodiversity oriented collection of plants which are thought to contain structural variants and decorations of these scaffolds. A liquid library of 3600 extracts will be generated and screened. Stringent prioritization and profiling procedures will generate 100 compounds as focused sub-libraries around the privileged scaffolds. A state-of-the-art technology platform for miniaturized natural product discovery will be used for the purpose. Evaluation of these sub-libraries will lead to 30 compounds which will undergo advanced testing to qualify 5 compounds as development candidates for novel agrochemical and/or cosmetic agents with new or improved properties over existing active ingredients. An additional outcome of the project will be an extract library with a unprecedented level of associated spectroscopic information and metadata, to be used for future purposes. The high-caliber consortium brings together international leaders in small molecule natural products, bioprospection, leading industries in agrochemistry, cosmetics, and spectroscopic data management and analysis.

Agency: Cordis | Branch: H2020 | Program: RIA | Phase: EO-1-2014 | Award Amount: 2.69M | Year: 2015

The main goal of the proposed project URBANFLUXES (URBan ANthrpogenic heat FLUX from Earth observation Satellites) is to investigate the potential of Earth Observation (EO) to retrieve anthropogenic heat fluxes. The main research question addresses whether EO is able to provide reliable estimates of anthropogenic heat flux spatiotemporal distribution, at local and city scales. URBANFLUXES will investigate the potential of EO to retrieve the anthropogenic heat flux, as a key component in the urban energy budget and by developing a method capable of deriving it from space. The objective is to develop a method that could be used operationally in the near future, when observations with adequate temporal resolution become available. URBANFLUXES EO-based approach will be easily transferable to any urban area and capable of providing anthropogenic heat flux benchmark data for different applications, including climate models to assess the implication of the anthropogenic heat on the Earth system; building energy models to characterize buildings-to-atmosphere/soil/water heat exchange pathways; and decision support systems for urban sustainable planning and mapping of emissions related to energy consumption. URBANFLUXES is therefore expected to prepare the ground for further innovative exploitation of European space data in scientific activities (Earth system modelling and climate change studies in cities) and future and emerging applications (sustainable urban planning) by exploiting the improved data quality, coverage and revisit times of the Copernicus Sentinels data. The Copernicus observations have the potential to reveal novel scientific insights, related to monitoring the anthropogenic heat flux in cities, at both local and regional scales, generating new EO opportunities. The URBANFLUXES products will therefore support both sustainable planning strategies to improve the quality of life in cities and Earth system models to provide more robust climate simulations.

Agency: Cordis | Branch: FP7 | Program: | Phase: | Award Amount: 3.92M | Year: 2008

The main objective of this project is to deploy the e-Infrastructures built so far by the EGEE and DILIGENT projects so that they address the needs of several new scientific communities affiliated with the broad disciplines of Environmental Monitoring and Fishery Resource Management. These e-Infrastructures, which offer mechanisms that concurrently exploit networks, grids, and data in a seamless fashion, will enable scientific communities to operate within a coherent pan-European model, regardless of the location of their research facilities. The project will progressively consolidate and expand these open e-Infrastructures to better address the needs of the two major target disciplines (which have challenging differences but also interesting commonalities). Thousands of scientists will obtain increasingly more facilities for creating Virtual Research Environments based on shared computation, storage, and generic service resources offered by EGEE and DILIGENT at a European level, as well as on data and domain-specific service resources offered by large international organizations, such as ESA, FAO, and CGIAR. The envisioned D4Science e-Infrastructure will have a multiplicative benefit to many scientific fields and will also act as a catalyst for the kind of cooperation and cross-fertilization among multiple communities that is necessary for addressing many grand challenges of science and society.

Agency: Cordis | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-2013-ITN | Award Amount: 3.47M | Year: 2013

Non-coding RNA (ncRNA) is a new research field in rapid development. It holds the potential to explain many fundamental biological phenomena and there is a vast prospective for the development of ncRNA-derived diagnostic and therapeutic tools. Hence, biotech and pharmaceutical companies are actively looking into this unexplored territory for novel targets. Therefore, there is a substantial and unmet need for the training of scientists in ncRNA biology, methodology and exploitation. The regions encompassing protein coding potential (exons) in humans only amount to 2% of the genome. New sequencing techniques have evidenced that mammalian genomes are pervasively transcribed and have revealed the existence of multiple classes of ncRNAs. Although our knowledge on the multitude of transcripts produced by the non-coding 98% of the genome is still very sketchy, pivotal roles have been established for ncRNAs in organismal development and homeostasis, in cellular proliferation, differentiation and apoptosis and in a broad range of human pathologies. Hence, there is a need to educate young scientists in this emerging and important research field. Aside from increasing our collective understanding of essential biological phenomena, ncRNA also constitute a vast and largely unexplored territory for the development of novel therapeutics and diagnostics. Accordingly, we propose to form a European RNA training network, RNATRAIN. This network will be devoted to educating the next generation of European researchers focusing on the functions and importance of ncRNAs in multidisciplinary projects in which the ncRNAs are studied in the context of development, differentiation and disease. Towards this, a group of 9 top-quality European research laboratories and 3 companies from 8 countries will train, to the best level, a cohort of early-stage researchers using cutting-edge technologies to dissect the functions and potentials of ncRNAs through integrated multidisciplinary projects.

Fusar-Poli P.,King's College London | Radua J.,King's College London | McGuire P.,King's College London | Borgwardt S.,King's College London | Borgwardt S.,University of Basel
Schizophrenia Bulletin | Year: 2012

Background: Despite impressive advancements in early interventions in psychosis, there is an urgent need of robust neurobiological markers to improve the predictive value of psychosis transition. Available structural imaging literature in the field is undermined by several methodological caveats and a number of confounders such as exposure to antipsychotic treatment. Methods: Fourteen voxel-based morphometry studies of antipsychotic-naive subjects at enhanced clinical risk for psychosis (high risk [HR]) or experiencing a first-episode psychosis (FEP) were included. Formal meta-analysis of effect sizes and "signed differential mapping" voxel-based meta-analysis were combined to control the results for sample sizes, strength of individual findings, and confounding variables. Results: Formal effect size meta-analysis indicated consistent gray matter (GM) reductions both in subjects at enhanced clinical risk for psychosis and in first-episode subjects when compared with control groups. Voxel-based meta-analysis showed GM reductions in the temporal, limbic prefrontal cortex within the HR group and in the temporal insular cortex and cerebellum within the FEP group. Psychosis onset was characterized by GM decreases in temporal, anterior cingulate, cerebellar, and insular regions. GM alterations in the temporal regions directly related to severity of psychotic symptoms. There was no publication bias. Heterogeneity across studies was low. Sensitivity analyses confirmed robustness of the above results. Conclusions: Vulnerability to psychosis is associated with consistent GM decreases in prefrontal and temporolimbic areas. The onset of full disease is accompanied by temporoinsular, anterior cingulate, and cerebellar GM reductions. Neuroanatomical alterations in temporal regions may underlie the clinical onset of psychotic symptoms. © The Author 2011.

Agency: Cordis | Branch: H2020 | Program: MSCA-ITN-EID | Phase: MSCA-ITN-2016 | Award Amount: 2.62M | Year: 2016

In PlantHUB will capture the academic, industrial and regulatory expertise from 5 world-class universities, 1 public research organisation, 1 governmental organization, 8 enterprises including 5 SMEs to train 10 ESRs in skills and competencies necessary to apply responsible research and innovation (RRI) in the area of plant breeding and production. We wish to address the demand of RRI leadership in plant science related research and diffusion of innovation. The individual research projects are demand-driven, responding to the needs of companies - particular SMEs - to increase R&I capacities. The outcomes are new molecular tools for plant breeding, new forage, cereal and oil crop varieties, non-invasive imaging and phenotyping technologies, intelligent lighting systems for plant growth, new software and services for complex genomic analyses, and plant product quality. PlantHUB industrial doctoral programme is ground-breaking in a number of respects: (i) doctoral training is placed into an entrepreneurial environment of leading public and private organisations (ii) it combines practical hands-on R&D and technology transfer in plant breeding and production with RRI training and practise. On completion of the training, graduates will have deep interdisciplinary knowledge of plant breeding, crop improvement, high-throughput technologies, isotope and big data analysis. In combination with a portfolio of transferable skills they will be able to take a lead in stakeholder & public engagement, innovation management, technology transfer and entrepreneurship. Our programme will become a flagship example at the forefront of intersectoral research, underpinned with a carefully created training curriculum to foster awareness, know-how, expertise and competence in RRI.

Agency: Cordis | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2016 | Award Amount: 3.90M | Year: 2017

We propose to forge a partnership between the leading European groups working on the next generation of solid state quantum emitters based on novel growth methods such as Droplet Epitaxy. Future, practical Nano-photonics and Quantum Circuits applications demand semiconductor quantum dots that can be grown on substrates with different lattice parameters (Si, Ge, GaAs), different substrate orientations (such as (001) and (111)) and tuneable optical, electrical and spin properties. All these requirements are met by high quality quantum dots grown with Droplet based Epitaxy techniques, circumventing the limitations of currently available systems based on strain-driven dot self-assembly. This vast novel research area at the crossroads of photonics, material science, quantum physics and nano-scale device fabrication will allow delivering top level multidisciplinary training to 15 early stage researcher (ESRs). The successful training of the ESRs by leading academic and 3 full industrial partners will be crucial for achieving the headline goals of this first ever consortium on droplet dot devices: (1) Entangled light emitting diodes with droplet dots grown on (111) substrates (2) Electrically triggered, droplet dot based single photon sources on Si/Ge substrates (3) Strain tuning in droplet dots without wetting layer: photon polarization and single spin control (4) Droplet Dot based single photon sources for non- classical light storage devices based on hybrid quantum systems (dots & laser-cooled atoms). The training and research progress will be discussed and monitored during the 4 project meetings, 3 summer schools and the final international conference on Droplet Dot Devices, all of which are open to the whole scientific community. We expect this network, based on the solid collaboration between growth groups, microscopists, quantum optics experimentalists and theorists to explore the full potential of this emerging technology.

ELASTISLET aims to create a breakthrough development in encapsulation technology and its use in cell and tissue therapies for the treatment of type 1 and 2 diabetes. ELASTISLET will combine leading technologies in biomaterial design, production and processing, cross-linking/grafting technology and cell therapy, to synergistically integrate them into a new immune-isolation and biomimetic scaffolding approach for islet and cell transplantation in diabetes treatment. ELASTISLETs starting point is a highly innovative and versatile family of superior biomaterials, the Elastin-like Recombinamers (ELRs). Those innovative materials will be combined with the most cutting-edge encapsulation technologies, such as reactive LbL. ELASTISLET relies on the most innovative ideas taken from synthetic biology, nanobiotechnology and molecular and cellular biology to build the ideal niche for islet/cell encapsulation and transplantation. ELASTISLET main objective is to achieve a functional coating that fulfils, first, the basic requirements of optimal biocompatibility and physical properties (permselectivity) but, second, generate a capsule that can promote an intense and directed cross talk through all cell-material interfaces involved: the implant-surrounding tissue (outer) interface and cargo cells-capsule (inner) interface. At the end, a capsule that is able not only to cloak its content and isolate it from the immune rejection but that it is able to biologically interact with the surrounding tissues and its cargo simultaneously in a way that the implanted capsule will immediately interact and fuse with the surrounding tissues creating a real continuity of the extracellular matrix from the core of the capsule to the surrounding hosts tissues and procuring adequate nutrient supply. That will provide a physiologically ideal biomimetic environment for the implanted islets/cells to survive and function in the long term without perceiving a foreign, unusual or hostile environment.

Agency: Cordis | Branch: H2020 | Program: RIA | Phase: PHC-15-2015 | Award Amount: 5.11M | Year: 2015

Spontaneous healing of articular cartilage injuries is poor and untreated defects predispose to osteoarthritis. Current therapies, including innovative autologous cell-based treatments, cannot predictably and reproducibly restore cartilage structure and function. BIOCHIP will carry out a multicenter, prospective phase II clinical trial to treat knee cartilage injuries using engineered grafts based on autologous nasal chondrocytes (NC). As compared to typically employed articular chondrocytes, NC have a higher and more reproducible capacity to generate mature cartilage tissues. Importantly, molecular/mechanical characterization, large size animal studies and a phase I trial carried out by BIOCHIP partners have already shown the compatibility of NC upon implantation in a joint, with promising preliminary clinical results. BIO-CHIPs specific objectives are: (1) To test the hypothesis that the maturation of NC-based cartilage grafts improves the clinical efficacy in the treatment of cartilage lesions (108 patients will be recruited to reach statistical significance) (2) To extend the range of clinical indications of NC-based grafts to so far untreatable pre-osteoarthritic lesions (kissing cartilage lesions in a sheep model) BIO-CHIP capitalizes on clinical experience of 4 reference centers for cartilage surgery, on established GMP manufacturing capacity and on preparation for commercial exploitation by a strong orthopedic device company. Demonstration of therapeutic efficacy of the new treatment will address a large clinical need (over 2 million cartilage defects/year worldwide), improve quality of life (reduce pain & disability in the young, delay prosthetic implants in the elderly), exploit a commercial opportunity (prospected revenues of up to 130 million /year) and reduce healthcare costs (estimated 12,000 healthcare savings/procedure). BIO-CHIP will consolidate the currently leading role of Europe in the development of cell-based cartilage regeneration strate.

News Article | December 5, 2016

A research team at the University of Basel's Biozentrum has investigated the expression of ribosomal proteins in a wide range of human tissues including tumors and discovered a cancer type specific signature. As the researchers report in Genome Biology this "cancer signature" could potentially be used to predict the progression of the disease. Proteins are the building blocks of life. They are produced by molecular machines, called ribosomes. A human ribosome contains some eighty ribosomal proteins. Prof. Mihaela Zavolan's research group at the Biozentrum of the University of Basel has now discovered that about a quarter of the ribosomal proteins have tissue-specific expression and that different cancer types have their own individual expression pattern of ribosomal proteins. In the future, these patterns may serve as a prognostic marker for cancer and may point towards new therapeutic opportunities. Ribosomes are responsible for protein synthesis and are thus essential for the cell. Therefore, it has long been assumed that the expression of the individual components of the ribosomes is strictly controlled and invariant. A few studies, however, have already suggested that the expression of individual ribosomal proteins is altered in cancers as well as in diseases of the hematopoietic system such as acute lymphoblastic leukemia. Mihaela Zavolan and her co-worker Joao Guimaraes have systematically analyzed ribosomal protein expression in thirty tissue types, three hundred different cell types and sixteen different types of tumors, such as lung and breast cancer. In contrast to previous assumptions, they found a wide variability in ribosomal protein gene expression. In particular, hematopoietic and tumor cells display the most complex expression pattern. "For us, it was really impressive to see that consistent signatures emerged for the different cancer types after the analysis of distinct data sets including patient samples," explains first author Guimaraes. "The pattern of the dysregulated proteins is very striking, whereby the expression of some ribosomal proteins is systematically reduced, and of others increased in cancer cells. This suggests that individual ribosomal proteins can either suppress or promote tumorigenesis." Furthermore, the scientists discovered a strong relationship between the "signature" in breast cancer and the relapse-free survival. "We were quite surprised to find that the expression level of just three ribosomal proteins allows a fairly accurate prognosis of disease progression, comparable to the best predictive markers that are currently known", Zavolan points out. "Our study demonstrates the potential of such expression signatures for the prognosis and perhaps a diagnosis of cancer. We are especially interested in studying the functions of individual ribosomal proteins and hopefully opening the door for new therapeutic options," explains the scientist. Joao C. Guimaraes and Mihaela Zavolan Patterns of ribosomal protein expression specify normal and malignant human cells Genome Biology (2016), doi: 10.1186/s13059-016-1104-z

News Article | February 15, 2017

For the first time, theoretical physicists from the University of Basel have calculated the signal of specific gravitational wave sources that emerged fractions of a second after the Big Bang. The source of the signal is a long-lost cosmological phenomenon called "oscillon". The journal Physical Review Letters has published the results. Although Albert Einstein had already predicted the existence of gravitational waves, their existence was not actually proven until fall 2015, when highly sensitive detectors received the waves formed during the merging of two black holes. Gravitational waves are different from all other known waves. As they travel through the universe, they shrink and stretch the space-time continuum; in other words, they distort the geometry of space itself. Although all accelerating masses emit gravitational waves, these can only be measured when the mass is extremely large, as is the case with black holes or supernovas. However, gravitational waves not only provide information on major astrophysical events of this kind but also offer an insight into the formation of the universe itself. In order to learn more about this stage of the universe, Prof. Stefan Antusch and his team from the Department of Physics at the University of Basel are conducting research into what is known as the stochastic background of gravitational waves. This background consists of gravitational waves from a large number of sources that overlap with one another, together yielding a broad spectrum of frequencies. The Basel-based physicists calculate predicted frequency ranges and intensities for the waves, which can then be tested in experiments. Shortly after the Big Bang, the universe we see today was still very small, dense, and hot. "Picture something about the size of a football," Antusch explains. The whole universe was compressed into this very small space, and it was extremely turbulent. Modern cosmology assumes that at that time the universe was dominated by a particle known as the inflaton and its associated field. The inflaton underwent intensive fluctuations, which had special properties. They formed clumps, for example, causing them to oscillate in localized regions of space. These regions are referred to as oscillons and can be imagined as standing waves. "Although the oscillons have long since ceased to exist, the gravitational waves they emitted are omnipresent - and we can use them to look further into the past than ever before," says Antusch. Using numerical simulations, the theoretical physicist and his team were able to calculate the shape of the oscillon's signal, which was emitted just fractions of a second after the Big Bang. It appears as a pronounced peak in the otherwise rather broad spectrum of gravitational waves. "We would not have thought before our calculations that oscillons could produce such a strong signal at a specific frequency," Antusch explains. Now, in a second step, experimental physicists must actually prove the signal's existence using detectors.

News Article | October 26, 2016

A year ago, the University of Zurich conducted its first parabolic flight for test purposes from Swiss soil. Now a second aircraft is ready for lift-off to research zero gravity: Saturday, an Airbus A310 ZERO-G is set to take off from the air force base in Dübendorf equipped with scientific experiments from the Universities of Zurich, Basel, Lucerne and ETH Zurich. The aircraft will perform special maneuvers to generate weightlessness in particular zones over the Mediterranean. On these trajectories - alternating between steep climbs and descents - the earth's gravitational pull will be overcome for periods of 22 seconds at a time. Diverse experiments can be conducted on board during these brief phases. Parabolic flights are vital for research under changed gravity: They can yield fundamental insights into the role of gravity in biological or physical processes. For instance, UZH is studying how human tissue reacts to the lack of oxygen in zero gravity - a key question for space walks; Lucerne University of Applied Sciences and Arts is using electrophysical tests to research the mechanisms involved in the perception of gravity by cells; a team of chiropractors from Balgrist University Hospital is testing functional connections in the development of back disorders, which can be identified more effectively in zero gravity; and another experiment conducted by ETH Zurich is devoted to the role of gravity in phytoplankton behavior, which should help improve our understanding of one of the most important oceanic microorganisms on earth. Besides these "terrestrial" experiments, however, one is also aimed into space: The University of Basel is testing sedimentation behavior in Mars' gravity, thereby obtaining crucial data for the calibration of mathematical models with a view to reconstructing the planet's environmental history. The research flight is also attractive for the space industry: An experiment conducted by the Swiss start-up SpacePharma is testing scientific hardware designed for use on small satellites. "Thanks to these research missions, Swiss Parabolic Flights, which were initiated by UZH, have taken root in Switzerland," says Professor Oliver Ullrich from the University of Zurich. He runs the Platform for Scientific Research in Zero Gravity, which is also backed by the Swiss Space Office of the State Secretariat for Education, Research and Innovation. The flexible combination of research from universities, industrial experiments and private individuals enables the costs of the flight to be minimized for science. These research flights into zero gravity are made possible by the close collaboration between Novespace, a subsidiary of the French space agency CNES, the Swiss Air Force, the Air Force Center in Dübendorf, Swissport and the Swiss SkyLab Foundation.

News Article | December 1, 2016

Majorana fermions are particles that could potentially be used as information units for a quantum computer. An experiment by physicists at the Swiss Nanoscience Institute and the University of Basel's Department of Physics has confirmed their theory that Majorana fermions can be generated and measured on a superconductor at the end of wires made from single iron atoms. The researchers also succeeded in observing the wave properties of Majoranas and, therefore, in making the interior of a Majorana visible for the first time. The results were published in the Nature journal npj Quantum Information. Around 75 years ago, Italian physicist Ettore Majorana hypothesized the existence of exotic particles that are their own antiparticles. Since then, interest in these particles, known as Majorana fermions, has grown enormously given that they could play a role in creating a quantum computer. Majoranas have already been described very well in theory. However, examining them and obtaining experimental evidence is difficult because they have to occur in pairs but are then usually bound to form one normal electron. Ingenious combinations and arrangements of various materials are therefore required to generate two Majoranas and keep them apart. The group led by Professor Ernst Meyer has now used predictions and calculations by theoretical physicists Professor Jelena Klinovaja and Professor Daniel Loss (from the Swiss Nanoscience Institute and the University of Basel's Department of Physics) to experimentally measure states that correspond to Majoranas. On a superconductor, the researchers evaporated single iron atoms with spin that, due to the row structure of the lead atoms, arrange themselves into a minute wire comprising one row of single atoms. The wires reached an astounding length of up to 70 nanometers. The researchers examined these mono-atomic chains with the aid of scanning tunneling microscopy and, for the first time, with an atomic force microscope as well. Using the images and measurements, they found clear indications of the existence of single Majorana fermions on the ends of the wires under certain conditions and from a specific wire length on. Despite the distance between them, the two Majoranas on the ends of the wires are still connected. Together, they form a new state extended across the whole wire that can either be occupied ("1") or not occupied ("0") by an electron. This binary property can then serve as the basis for a quantum bit (Qubit) and means that Majoranas, which are also very robust against a number of environmental influences, are promising candidates for creating a future quantum computer. The researchers from Basel have not only shown that single Majoranas can be generated and measured at the ends of an iron wire, they also performed the first experiment to show that Majoranas are extended quantum objects with an inner structure, as predicted by their theory colleagues. Over an area of several nanometers, the measurements showed the expected wavefunction with characteristic oscillations and twofold decay lengths, which have now been made visible for the first time. Rémy Pawlak, Marcin Kisiel, Jelena Klinovaja, Tobias Meier, Shigeki Kawai, Thilo Glatzel, Daniel Loss, and Ernst Meyer Probing atomic structure and Majorana wavefunctions in mono-atomic Fe chains on superconducting Pb surface npj Quantum Information (2016), doi: 10.1038/npjqi.2016.35

News Article | December 14, 2016

The latest recipients of Germany's most prestigious research funding prize have been announced. In Bonn today, the Joint Committee of the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) chose ten researchers, three women and seven men, to receive the 2017 Leibniz Prize. The recipients of the prize were selected by the Nominations Committee from 134 nominees. Of the ten new prizewinners, three are from the natural sciences, three from the humanities and social sciences, two from the life sciences and two from the engineering sciences. Each of the ten winners will receive €2.5 million in prize money. They can use these funds for their research work in any way they wish, without bureaucratic obstacles, for up to seven years. The awards ceremony for the 2017 Leibniz Prizes will be held on 15 March in Berlin. The following researchers will receive the 2017 "Funding Prize in the Gottfried Wilhelm Leibniz Programme" awarded by the DFG: The Gottfried Wilhelm Leibniz Prize has been awarded by the DFG annually since 1986. Each year a maximum of ten prizes can be awarded, each with prize money of €2.5 million. With the ten prizes for 2017, a total of 348 Leibniz Prizes have been awarded to date. Of these, 115 were bestowed on researchers in the natural sciences, 101 in the life sciences, 79 in the humanities and social sciences, and 53 in the engineering sciences. The number of award recipients is higher than the number of awarded prizes because, in exceptional cases, the prizes and money can be shared. Accordingly, a total of 374 nominees have received the prize, including 326 men and 48 women. The Leibniz Prize is the most significant research prize in Germany. Seven past prizewinners have subsequently received the Nobel Prize: 1988 Professor Dr. Hartmut Michel (Chemistry), 1991 Professor Dr. Erwin Neher and Professor Dr. Bert Sakmann (Medicine), 1995 Professor Dr. Christiane Nüsslein-Volhard (Medicine), 2005 Professor Dr. Theodor W. Hänsch (Physics), 2007 Professor Dr. Gerhard Ertl (Chemistry) and most recently in 2014 Professor Dr. Stefan W. Hell (Chemistry). Professor Dr. Lutz Ackermann (43), Organic Molecular Chemistry, Institute of Organic and Biomolecular Chemistry, University of Göttingen Lutz Ackermann has been selected for the 2017 Leibniz Prize for his outstanding work in the field of organic chemistry. His international reputation is based especially on his research into the catalytic activation of carbon-hydrogen bonds. These bonds, which occur in all organic substances, are usually extremely inert and permit only very poor and frequently non-selective transformation. The methods developed by Ackermann and his colleagues have paved the way for fundamentally new and low-impact manufacturing methods for important chemical products including active substances, agrochemicals and fine chemicals. Through his other work, Ackermann has also created new concepts for environmentally friendly chemical synthesis. Lutz Ackermann studied chemistry in Kiel, and, after further studies in Rennes and Mülheim an der Ruhr, he obtained his doctorate from the University of Dortmund. He did postdoctoral research at Berkeley before going to Munich in 2003 to work as the leader of a DFG-funded Emmy Noether independent junior research group. Ackermann has held his current chair in Göttingen since 2007 and has headed the Institute of Organic and Biomolecular Chemistry there since 2015. He is one of the most frequently cited researchers in his field in the world. Professor Dr. Beatrice Gründler (52), Arabic Studies, Seminar for Semitic and Arabic Studies, Free University of Berlin Beatrice Gründler will receive the Leibniz Prize for her studies on the diversity of voices in Arabic poetry and culture. She has been interested in the medium of script and its fundamental importance to Arabic traditions since an early stage in her career, as evidenced for example by her book "The Development of the Arabic Script" (1993). Through her research she has developed a complex media history of the Arab world, from the introduction of paper to book printing and beyond - indeed, she refers to an 'Arabic book revolution'. In a pilot project for a critical, annotated digital edition of the "Kalila wa-Dimna", begun in 2015, Gründler has unravelled the history of the text, development and impact of this collection of fables, considered one of the earliest Arabic prose works and a central text of Arabic wisdom literature. Gründler's own approach puts into practice in an exemplary way the encounters between Arabic and European knowledge traditions that she investigates in her work - another reason for the importance of her research. Beatrice Gründler studied at Strasbourg, Tübingen and Harvard, where she received her doctorate in 1995. After a period at Dartmouth College, she began teaching at Yale University in 1996, first as an assistant professor and from 2002 as Professor of Arabic Literature. In 2014 she returned to Germany, and has since been undertaking research at the Free University of Berlin. Ralph Hertwig will be recognised with the 2017 Leibniz Prize for his pioneering work in the psychology of human judgement and decision-making. His research has expanded our understanding of the possibilities and limitations of human rationality. Hertwig investigates the strategies which humans use, faced with limited knowledge, limited cognitive resources and often limited time, to nonetheless make good decisions and organise their actions. Central to his work is the question why a limitation also constitutes a strength, in other words how adaptive heuristics, as simple rules of thumb for problem-solving, can be as effective as complex optimisation models. Another of Hertwig's important contributions to decision research is the distinction between experience-based and description-based assessment of risk. This explains why the dramatic consequences of climate change, for example, are systematically underestimated by society, because although there is plenty of information available to describe the problem, there is little everyday experience - the main thing that people base their decisions on. Ralph Hertwig has been the director of the Max Planck Institute for Human Development since 2012 and heads the Center for Adaptive Rationality. Hertwig began his scientific career in 1995 at the Max Planck Institute for Psychological Research in Munich. In 1997 he moved to the Max Planck Institute in Berlin. Between 2000 and 2002 he was a Research Fellow at Columbia University. In 2003 he obtained his habilitation from the Free University of Berlin. In 2005 he was appointed Professor of Cognitive Science and Decision Psychology at the University of Basel, and moved from there to his current position. Karl-Peter Hopfner will receive the Leibniz Prize for his outstanding work in structural molecular biology and genome biology, with which he has made pioneering contributions to the field of DNA repair and the cellular detection of foreign nucleic acids. Hopfner's research focused on the molecular mechanisms of multiprotein complexes, which play an important role in the detection of damaged or viral nucleic acids. These detection processes are crucial to the protection of the genome; errors in detection and repair are among the main reasons for the development of cancer. Building on that work, Hopfner has carried out essential work on DNA double-strand break repair and in recent years has decoded the mechanism of the central MRN complex Mre11-Rad50-Nbs1, a DNA damage sensor. He also contributed substantially to answering the question of how cellular sensors of the innate immune system recognise viral or bacterial nucleic acids in the case of infection. Here, the sensors must distinguish between the body's own RNA and foreign RNA. Karl-Peter Hopfner studied biology in Regensburg and in St. Louis, USA. He completed his doctorate at the Max Planck Institute for Biochemistry in Martinsried as part of the Division led by Nobel Prize winner Robert Huber. Between 1999 and 2001 he carried out postdoctoral research at the Scripps Research Institute in La Jolla, before accepting a tenure track professorship at the Gene Center at LMU Munich. He has been a full professor at LMU since 2007. Professor Dr. Frank Jülicher (51), Theory of Biological Physics, Max Planck Institute for the Physics of Complex Systems, Dresden The award of the Leibniz Prize to Frank Jülicher recognises a world-leading researcher in biophysics with the ability to identify universal physical principles in the complex world of living matter. He had already attracted attention with his early work on the physics of hearing and cell mechanics. Through his investigation of active matter - the components of which exhibit autonomous activity, such as molecular motors, which play a key role in cell movement and division - Jülicher has established a new field of research. This raises many fundamental questions in non-equilibrium physics and has also inspired numerous new applications as well as biomimetic design. In collaboration with French researchers, the biophysicist laid the foundations for the dynamics of active matter by formulating a general hydrodynamic theory of active matter. Most recently, Jülicher has turned his attention to the control and organisation of cells in tissue. His seminal work is contributing to our understanding of cell self-organisation in tissue. This phenomenon, as yet poorly understood, is of enormous importance to developmental biology and medical applications. Frank Jülicher studied physics in Stuttgart and Aachen, received his doctorate in Cologne in 1994 and then spent two years researching in the USA and Canada. He subsequently worked with leading researchers in Paris in the field of soft matter and biophysics, before obtaining his habilitation in 2000 at Paris Diderot University (Paris 7). Since 2002, Jülicher has been the director of the Max Planck Institute for the Physics of Complex Systems in Dresden and Professor of Biophysics at the Technical University of Dresden. Professor Dr. Lutz Mädler (45), Mechanical Process Engineering, Stiftung Institut für Werkstofftechnik (IWT) and Department of Production Engineering, University of Bremen Lutz Mädler will receive the Leibniz Prize in recognition of his pioneering work in the targeted reactive formation of nanoparticles in the gas phase and their effect on living matter. He has developed an improved variant of flame spray pyrolysis for the cost-effective synthesis of nanoparticles, involving the thermochemical splitting of organic compounds. His work has made flame spray pyrolysis available for industrial applications. Mädler subsequently refined this pyrolysis technique when he discovered the droplet explosion phenomenon in flame sprays and its effects on material synthesis. However, as well as looking at the tailored synthesis of nanoparticles, Mädler has also investigated how toxic these particles are to the human body. This is important because many applications, for example paints, textiles and dental fillings, have direct impacts on humans. Mädler was able to demonstrate that interactions between synthetic nanoparticles and biological tissue produce reactive oxygen species which can trigger undesirable reactions. Lutz Mädler studied physics at the Technical University of Zwickau and then process engineering at Technische Universität Bergakademie Freiberg, where he obtained his doctorate in 1999. He completed his habilitation at ETH Zurich and then, with the support of a DFG fellowship, became a Senior Researcher at the University of California, Los Angeles. In 2008 he was appointed professor at the University of Bremen. Britta Nestler has been selected to receive the 2017 Leibniz Prize for her significant, internationally recognised research in computer-assisted materials research and the development of new material models with multiscale and multiphysical approaches. Nestler has developed extremely flexible and high-performing simulation environments to simulate the microstructure of materials for use on supercomputers. These are based on her own quantitative models for the description of multicomponent systems. She has thus achieved a new quality of microstructure representation in the thermomechanical simulation of materials and the simulation of solidification processes and thus depicted these processes through realistic 3D simulation for the first time. Through her creative application and further development of the phase field method, Nestler has achieved outstanding fundamental insights which are also of enormous practical relevance. For example, her simulation calculations are used to predict the spread of cracks in design materials such as brake discs and therefore help to extend their lifetime. Britta Nestler studied physics and mathematics in Aachen, where she also received her doctorate. Research visits took her to Southampton, UK and Paris. In 2001 Nestler accepted a professorship in the Faculty of Computer Science at Karlsruhe University of Applied Sciences and in 2009 her current chair at KIT. Professor Dr. Joachim P. Spatz (47), Biophysics, Max Planck Institute for Intelligent Systems, Stuttgart, and Institute of Physical Chemistry, University of Heidelberg Joachim Spatz will be recognised with the Leibniz Prize for his outstanding research at the boundaries of materials sciences and cell biophysics. His research is concerned with cell adhesion, that is, the adhesion and bonding of cells to one another and to surfaces. His exemplary experimental approach has garnered precise insights into the control of cell adhesion and indeed physiological processes. To achieve this, Spatz used artificial, molecularly structured boundary surfaces to reduce possible interactions to a minimum of molecular components. Joachim Spatz' scientific achievement lies in the fact that he can study the communication mechanisms between cells in a new way with the help of concepts from materials science and physics. Using these resources, he was able to explain how the molecular mechanism of collective cell migration works in wound healing. Joachim Spatz studied physics in Ulm and at Colorado State University. He obtained his doctorate in macromolecular chemistry in Ulm, and it was also there that he completed his habilitation with a topic on cell mechanics. Since 2000 he has been a professor of biophysical chemistry in Heidelberg. In 2004 he was appointed director of the Max Planck Institute for Metals Research, now the Max Planck Institute for Intelligent Systems, in Stuttgart. Since 2008 he has also held a visiting professorship in molecular cell biology at the Weizmann Institute in Rehovot, Israel. Professor Dr. Anne Storch (48), African Studies, Institute for African Studies and Egyptology, University of Cologne In awarding the 2017 Leibniz Prize to Anne Storch, the DFG is honouring an extremely innovative and world-renowned researcher in African Studies who has contributed to a far-reaching reorientation of her field through her pioneering work. Drawing on questions and methods from cultural anthropology and the social sciences, Storch has introduced new thematic and methodological dimensions, both theoretical and practical, to African Studies. Her exemplary studies have also shown how linguistically based analyses can be used in an interdisciplinary approach to develop a cultural-anthropological understanding of contemporary Africa. Of particular significance was her study of taboos and secret languages in central Africa, published in 2011, which describes linguistic observations in such a way that they lead to complex sociological descriptions of power practices and political mechanisms of effect. Storch's case studies, rooted in, yet transcending, linguistic speech description, have become internationally significant model studies for a modern, self-critical approach to African Studies. Anne Storch has been Professor of African Studies in Cologne since 2004. She trained in anthropology, African Studies, Oriental Studies and archaeology in Frankfurt am Main and Mainz. Between 2006 and 2009 she served as president of the Fachverband Afrikanistik, the specialist society for Africa-related scholarship in Germany. Since 2014 she has been the president of the International Association for Colonial and Postcolonial Linguistics. Awarding the Leibniz Prize to Jörg Vogel recognises one of the world's leading researchers in the field of ribonucleic acid biology. He was selected for his pioneering contributions to our understanding of regulatory RNA molecules in infection biology. Vogel recognised the importance of RNA biochemistry in prokaryotes very early on and has done pioneering work in the application and development of high-throughput sequencing for RNA analysis. Using this method, he has studied the influence of pathogens on the host cell. Vogel has also discovered how small regulatory RNA molecules control protein synthesis and the breakdown of RNA. This in turn has contributed to the development of new methods which can be used in gene therapy. Together with Emmanuelle Charpentier, who won the Leibniz Prize in 2016, Vogel was able to understand tracrRNA (trans-activating RNA) and its function, which made the application of the CRISPR/Cas9 system possible. Vogel thus uncovered general biological principles which play a major role in our understanding of pathogenic microorganisms and are resulting in new treatment approaches. Jörg Vogel studied biochemistry at the Humboldt University of Berlin, where he also obtained his doctorate on RNA splicing in plants. After doing postdoctoral research in Uppsala and Jerusalem, in 2004 he was appointed Head of Division at the Max Planck Institute for Infection Biology in Berlin. Since 2009 he has been a professor at the University of Würzburg, where he heads the Institute for Molecular Infection Biology. The Leibniz Prizes will be awarded on 15 March 2017 at 3.00 pm at the Berlin-Brandenburg Academy of Sciences and Humanities in Berlin. A separate invitation will be sent to members of the media. Additional information about the 2017 prizewinners can be requested at the start of the new year by contacting the DFG Press and Public Relations Office or at http://www. . Detailed information about the Gottfried Wilhelm Leibniz Programme is available at: http://www.

News Article | December 7, 2016

Before an operation, surgeons have to obtain the most precise image possible of the anatomical structures of the part of the body undergoing surgery. University of Basel researchers have now developed a technology that uses computed tomography data to generate a three-dimensional image in real time for use in a virtual environment. The planning of a surgical procedure is an essential part of successful treatment. To determine how best to carry out procedures and where to make an incision, surgeons need to obtain as realistic an image as possible of anatomical structures such as bones, blood vessels, and tissues. Researchers from the University and University Hospital of Basel's Department of Biomedical Engineering have now succeeded in taking two-dimensional cross-sections from computer tomography and converting them for use in a virtual environment without a time lag. Using sophisticated programming and the latest graphics cards, the team led by Professor Philippe C. Cattin succeeded in speeding up the volume rendering to reach the necessary frame rate. In addition, the SpectoVive system can perform fluid shadow rendering, which is important for creating a realistic impression of depth. For example, doctors can use the latest generation of virtual reality glasses to interact in a three-dimensional space with a hip bone that requires surgery, zooming in on the bone, viewing it from any desired angle, adjusting the lighting angle, and switching between the 3D view and regular CT images. Professor Cattin explains the overall benefits: "Virtual reality offers the doctor a very intuitive way to obtain a visual overview and understand what is possible." "This brand-new technology smoothly blurs the boundary between the physical world and computer simulation. As a doctor, I am no longer restricted to looking at my patient's images from a bird's eye view. Instead, I become part of the image and can move around in digital worlds to prepare myself, as a surgeon, for an operation in detail never seen before," says ophthalmologist Dr. Peter Maloca. "I have found that these new environments continue to guide me and have helped rewire my senses, ultimately making me a better doctor. Those who stand to gain the most here are doctors, their patients, and students - all of whom can share in this new information," adds Maloca, who works at University Hospital Basel's OCTlab and at Moorfields Eye Hospital in London. The ability to convert CT images into a 3D on-screen representation is nothing new. Until now, however, commonly available hardware could not generate these three-dimensional volumes in real time for use in virtual spaces. One particularly challenging aspect was that smooth playback in a virtual environment requires at least 180 images a second - 90 images each for the left and right eyes; otherwise, the viewer may experience nausea or dizziness. This achievement was aided by developments in the computer games industry and new generations of powerful standard hardware, providing medical practitioners with access to three-dimensional test environments. At present, the Basel-based researchers are conducting regular demonstrations of SpectoVive to physicians in order to highlight the system's potential and, at the same time, to gain a better understanding of doctors' requirements. Some museums have also expressed interest in the technology, seeing SpectoVive as an opportunity to allow visitors to discover the world inside exhibits, such as mummies, in an intuitive and nondestructive manner. However, Philippe Cattin, Professor for Image-Guided Therapy at the Faculty of Medicine, sees the greatest potential in the areas of diagnostics, surgical planning, and medical training. This innovation is part of the MIRACLE project underway at the Department of Biomedical Engineering. The project is receiving CHF 15.2 million in funding from the Werner Siemens-Foundation. Its aim is to allow the minimally invasive treatment of bones using laser beams. One day, it is expected that SpectoVive technology will be used in the planning of surgical procedures and for the navigation of the robot-guided laser system.

News Article | February 28, 2017

After three rounds of competition -- one of which involved a public vote -- a software tool developed by researchers at Fred Hutchinson Cancer Research Center and the University of Basel to track Zika, Ebola and other viral disease outbreaks in real time has won the first-ever international Open Science Prize. Fred Hutch evolutionary biologist Dr. Trevor Bedford and physicist and computational biologist Dr. Richard Neher of the Biozentum Center for Molecular Life Studies in Basel, Switzerland, designed a prototype called nextstrain to analyze and track genetic mutations during the Ebola and Zika outbreaks. Using the platform Bedford and Neher built, anyone can download the source code from the public-access code-sharing site GitHub, run genetic sequencing data for the outbreak they are following through the pipeline and build a web page showing a phylogenetic tree, or genetic history of the outbreak, in a few minutes, Bedford said. He and Neher envision the tool as adaptable for any virus -- a goal to which they will apply the $230,000 prize announced today by its three sponsors, the U.S. National Institutes of Health, the British-based charitable foundation Wellcome Trust and the U.S.-based Howard Hughes Medical Institute. "Everyone is doing sequencing, but most people aren't able to analyze their sequences as well or as quickly as they might want to," Bedford said. "We're trying to fill in this gap so that the World Health Organization or the U.S. Centers for Disease Control and Prevention -- or whoever -- can have better analysis tools to do what they do. We're hoping that will get our software in the hands of a lot of people." For now, the tool is easy to use for Zika and Ebola. (The researchers also built a separate platform called nextflu for influenza.) But adapting the platform for other pathogens still involves a fair amount of work and technical skill, so Bedford is working with a web developer to "get that bar down so it will be easier to have this built out for other things." By lowering the technical bar, he and Neher hope to nudge researchers to overcome another obstacle: a longstanding reluctance to share data. That is also a goal of the Open Science Prize. "Open science" supporters believe, as Bedford and Neher do, that sharing preliminary information quickly speeds discoveries, including those that could improve human health, and is therefore good for both science and society. The Open Science Prize competition aimed to stimulate the development of ground-breaking tools and platforms to make it easier for researchers and the wider public to share and find publications, datasets, code and other research outputs as well as to "generate excitement, momentum and further investment" in doing so, according to the prize sponsors. Nextstrain "is an exemplar of open science and will have a great impact on public health by tracking viral pathogens," said Robert Kiley, who leads Wellcome's work on open research, in a statement. All of the Open Science Prize entrants "demonstrated what's possible when data and code are made open for all," he said. Bedford and Neher were among six teams of finalists chosen in May from 96 entries representing 450 innovators and 45 countries. In January, a public vote (3,730 votes from 76 countries, to be precise) narrowed the field to three. Bedford praised both runner-up teams as doing "really fantastic work." MyGene2 is designed to help people with rare diseases share health and genetic information with other families, clinicians and researcher worldwide. OpenTrialsFDA is aimed at making it easier to find information from clinical trials that was reported to the federal Food and Drug Administration but never published in academic journals. For all of its cutting-edge technology, nextstrain, the winning project, belongs to a long tradition of using data visualization to understand -- and intervene in -- outbreaks, dating back to the 1854 London cholera outbreak. At the time, cholera, an infectious and often fatal intestinal disease, was thought to be spread by "miasma" or bad-smelling air. Dr. John Snow, the "father of modern epidemiology," the study of the causes and patterns of disease, suspected the disease was spread by contaminated water. He drew a map of public well sites and cholera cases and noted that cases clustered around a particular well. The map, Bedford said, made an intervention -- removing the handle of the Broad Street water pump -- obvious. "What we're doing with nextstrain is meant to be in this tradition," he said. "Right now it's more of a 'now-cast,' but we really want to be doing a real-time forecast of what's going on with an epidemic." Evolutionary and computational biologists like Bedford and Neher are in the open science movement's vanguard. One reason is that their fields are the ones most concerned with outbreaks, where waiting to publish can have deadly consequences. Real-time tracking of genetic mutations during disease outbreaks helps scientists discern what makes viruses so severe and inform public health efforts to contain them. Being able to do so depends on researchers openly sharing the genetic sequencing data, something that not all scientists embrace in a competitive world where researchers rush to publish in prestigious journals and stake claims to discoveries. The seed for nextstrain sprouted while Bedford was doing postdoctoral research at the University of Michigan. He had published a paper on flu migration using data up to 2010. He found himself thinking what a pity it was that the analysis couldn't be updated as new data came out. But the fact that a paper had already been published was a disincentive for anyone to write a new paper with just a small update to the data. From that frustration, nextflu was born. And nextflu led to nextstrain. The devastating 2013-2016 Ebola epidemic in West Africa leant the project new urgency. Relatively early in the outbreak, researchers sequenced Ebola genomes from patients and immediately uploaded them to the public database GenBank, leading to a surge of collaboration from experts in diverse fields. The collection of shared, publically available data helped answer critically important questions as the epidemic was unfolding. It added to the confirmation that that the outbreak was being sustained by human-to-human contact, not contact with bats or other animal carriers, suggested probable transmission routes and revealed where and how fast mutations in the virus were occurring -- all information crucial to both public health and medical interventions. Even when data is shared, speed is everything in responding to outbreaks, so any tool that speeds data analysis contributes to the effort. But despite the precedent set by the response to the Ebola epidemic, fewer researchers have shared Zika virus genome sequences from the more recent crisis in Brazil, Central America and the Caribbean, the researchers said. "I'm not seeing the same thing with Zika," said Dr. Gytis Dudas, a postdoctoral fellow in Bedford's laboratory who worked on many of the Ebola analyses. In part, Dudas said, the Zika virus is more difficult to sequence than Ebola, making researchers more likely to guard their rare sequences for publications. And that, Bedford said, is "a tragedy," even as he understands that academic careers depend on publishing. "The idea is that this nextstrain platform would provide some neutral ground with which to share data," said Bedford. "We're not trying to make a flashy paper. We just want [the data] to be on the website so people can look at the latest thing and do analyses that aren't stymied by publication practices. This kind of simple sequence sharing during outbreaks is something that if you could just push the [scientific] community a little bit, you could have some real-world impact in helping respond to epidemics."

Weber W.,Albert Ludwigs University of Freiburg | Fussenegger M.,ETH Zurich | Fussenegger M.,University of Basel
Nature Reviews Genetics | Year: 2012

Synthetic biology aims to create functional devices, systems and organisms with novel and useful functions on the basis of catalogued and standardized biological building blocks. Although they were initially constructed to elucidate the dynamics of simple processes, designed devices now contribute to the understanding of disease mechanisms, provide novel diagnostic tools, enable economic production of therapeutics and allow the design of novel strategies for the treatment of cancer, immune diseases and metabolic disorders, such as diabetes and gout, as well as a range of infectious diseases. In this Review, we cover the impact and potential of synthetic biology for biomedical applications. © 2011 Macmillan Publishers Limited. All rights reserved.

Vukmirovic N.,University of Belgrade | Bruder C.,University of Basel | Stojanovic V.M.,University of Basel
Physical Review Letters | Year: 2012

We consider electron-phonon coupling in crystalline organic semiconductors, using naphthalene for our case study. Employing a first-principles approach, we compute the changes in the selfconsistent Kohn-Sham potential corresponding to different phonon modes and go on to obtain the carrier-phonon coupling matrix elements (vertex functions). We then evaluate perturbatively the quasiparticle spectral residues for electrons at the bottom of the lowest unoccupied (LUMO), and holes at the top of the highest occupied (HOMO), band, obtaining Z e≈0.74 and Z h≈0.78, respectively. Along with the widely accepted notion that the carrier-phonon coupling strengths in polyacenes decrease with increasing molecular size, our results provide strong microscopic evidence for the previously conjectured nonpolaronic nature of bandlike carriers in these systems. © 2012 American Physical Society.

Hamaratoglu F.,University of Lausanne | Affolter M.,University of Basel | Pyrowolakis G.,Albert Ludwigs University of Freiburg
Seminars in Cell and Developmental Biology | Year: 2014

Decapentaplegic (Dpp), the fly homolog of the secreted mammalian BMP2/4 signaling molecules, is involved in almost all aspects of fly development. Dpp has critical functions at all developmental stages, from patterning of the eggshell to the determination of adult intestinal stem cell identity. Here, we focus on recent findings regarding the transcriptional regulatory logic of the pathway, on a new feedback regulator, Pentagone, and on Dpp's roles in scaling and growth of the Drosophila wing. © 2014 The Authors.

Fruzzetti F.,Ospedale S. Chiara | Bitzer J.,University of Basel
Contraception | Year: 2010

Previous attempts to replace ethinylestradiol (EE) with 17β-estradiol (E2) in combined oral contraceptives (COCs) have proved unsatisfactory in terms of bleeding outcomes. A review of previous studies of E2-based COCs has shown that, despite good ovulation inhibition, bleeding irregularities affected up to 100% of women, often resulting in high rates of discontinuation (up to 42%). Suggested reasons for the bleeding irregularities observed with these predominantly monophasic estradiol-progestin preparations included suboptimal doses of E2 and an inappropriate estrogen/progestin ratio. The progestin used in the investigated formulations (e.g., norethisterone acetate, desogestrel and cyproterone acetate) may also have affected the overall bleeding profile. More recent studies of a multiphasic COC containing estradiol valerate (E2V) and dienogest (DNG) indicate efficient ovulation inhibition and acceptable cycle control. In a randomized, double-blind trial that compared E2V/DNG with a monophasic COC comprising EE/levonorgestrel (LNG), the occurrence of scheduled withdrawal bleeding per cycle with E2V/DNG and EE/LNG was 77.7-83.2% and 89.5-93.8%, respectively. The intensity and duration of withdrawal bleeding was reduced with E2V/DNG. The incidence of intracyclic bleeding was similar with E2V/DNG (10.5-18.6%) and EE/LNG (9.9-17.1%). This review shows that after several unsatisfactory attempts to develop E2-based COCs, more recent studies employing endometrial-focused progestins, e.g., DNG, and multiphasic dosing regimens appear to be a promising approach for an E2-based COC that provides efficient ovulation inhibition and acceptable cycle control. © 2010 Elsevier Inc. All rights reserved.

Pulliainen A.T.,University of Turku | Dehio C.,University of Basel
FEMS Microbiology Reviews | Year: 2012

Bartonella spp. are facultative intracellular bacteria that typically cause a long-lasting intraerythrocytic bacteremia in their mammalian reservoir hosts, thereby favoring transmission by blood-sucking arthropods. In most cases, natural reservoir host infections are subclinical and the relapsing intraerythrocytic bacteremia may last weeks, months, or even years. In this review, we will follow the infection cycle of Bartonella spp. in a reservoir host, which typically starts with an intradermal inoculation of bacteria that are superficially scratched into the skin from arthropod feces and terminates with the pathogen exit by the blood-sucking arthropod. The current knowledge of bacterial countermeasures against mammalian immune response will be presented for each critical step of the pathogenesis. The prevailing models of the still-enigmatic primary niche and the anatomical location where bacteria reside, persist, and are periodically seeded into the bloodstream to cause the typical relapsing Bartonella spp. bacteremia will also be critically discussed. The review will end up with a discussion of the ability of Bartonella spp., namely Bartonella henselae, Bartonella quintana, and Bartonella bacilliformis, to induce tumor-like vascular deformations in humans having compromised immune response such as in patients with AIDS. © 2012 Federation of European Microbiological Societies.

Simmler L.D.,University of Basel | Rickli A.,University of Basel | Hoener M.C.,Hoffmann-La Roche | Liechti M.E.,University of Basel
Neuropharmacology | Year: 2014

Psychoactive β-keto amphetamines (cathinones) are sold as "bath salts" or "legal highs" and recreationally abused. We characterized the pharmacology of a new series of cathinones, including methedrone, 4-methylethcathinone (4-MEC), 3-fluoromethcathinone (3-FMC), pentylone, ethcathinone, buphedrone, pentedrone, and N,N-dimethylcathinone. We investigated norepinephrine (NE), dopamine (DA), and serotonin (5-HT) uptake inhibition using human embryonic kidney 293 (HEK 293) cells that express the respective human monoamine transporter, the drug-induced efflux of NE, DA, and 5-HT from monoamine-preloaded cells, and binding affinity to monoamine transporters and receptors. All of the cathinones were potent NE uptake inhibitors but differed in their DA vs. 5-HT transporter inhibition profiles and monoamine release effects. Methedrone was a more potent 5-HT than DA transporter inhibitor and released NE and 5-HT similar to para- methoxymethamphetamine (PMMA), para-methoxyamphetamine (PMA), 4-methylthioamphetamine (4-MTA), and 3,4-methylenedioxymethamphetamine (MDMA). 4-MEC and pentylone equipotently inhibited all of the monoamine transporters and released 5-HT. Ethcathinone and 3-FMC inhibited NE and DA uptake and released NE, and 3-FMC also released DA similar to N-ethylamphetamine and methamphetamine. Pentedrone and N,N-dimethylcathinone were non-releasing NE and DA uptake inhibitors as previously shown for pyrovalerone cathinones. Buphedrone preferentially inhibited NE and DA uptake and also released NE. None of the cathinones bound to rodent trace amine-associated receptor 1, in contrast to the non-β-keto-amphetamines. None of the cathinones exhibited relevant binding to other monoamine receptors. In summary, we found considerable differences in the monoamine transporter interaction profiles among different cathinones and compared with related amphetamines. © 2013 Elsevier Ltd. All rights reserved.

Rotzler J.,University of Basel | Mayor M.,University of Basel | Mayor M.,Karlsruhe Institute of Technology
Chemical Society Reviews | Year: 2013

This tutorial review summarizes the progress made towards mechanically interlocked daisy chains. Such materials can be seen as a further development in polymer science, where the conventional covalent interlinking bonds are replaced by supramolecular binding concepts. Materials in which the mechanical bond is an integral part of the polymeric backbone are expected to possess unique macroscopic properties and are therefore the synthetic aim in an ever growing research community. After introducing general considerations about daisy chains, the most common analytic methods to get insight into the aggregation behaviour of such self-complementary monomers are presented. Cyclodextrins/aromatic rods, crown ethers/cationic rods and pillararenes/alkyl chains are systems used to achieve daisy chain-like molecular arrays. By comparison of the reported systems, conclusions about an improved structural design are drawn.

Medinger M.,University of Basel | Mross K.,Albert Ludwigs University of Freiburg
Journal of Angiogenesis Research | Year: 2010

New blood vessel formation (angiogenesis) is not only essential for the growth of solid tumors but there is also emerging evidence that progression of hematological malignancies like multiple myeloma, acute leukemias, and myeloproliferative neoplasms, also depends on new blood vessel formation. Anti-angiogenic strategies have become an important therapeutic modality for solid tumors. Several anti-angiogenic agents targeting angiogenesis-related pathways like monoclonal antibodies, receptor tyrosine kinase inhibitors, immunomodulatory drugs, and proteasome inhibitors have been entered clinical trials or have been already approved for the treatment of hematological malignancies as well and in some instances these pathways have emerged as promising therapeutic targets. This review summarizes recent advances in the basic understanding of the role of angiogenesis in hematological malignancies and clinical trials with novel therapeutic approaches targeting angiogenesis. © 2010 Medinger and Mross; licensee BioMed Central Ltd.

Weigel M.,Albert Ludwigs University of Freiburg | Weigel M.,University of Basel
Journal of Magnetic Resonance Imaging | Year: 2015

The extended phase graph (EPG) concept represents a powerful tool for depicting and understanding the magnetization response of a broad variety of MR sequences. EPGs focus on echo generation as well as on classification and use a Fourier based magnetization description in terms of "configurations states". The effect of gradients, radiofrequency (RF) pulses, relaxation, and motion phenomena during the MR sequence is characterized as the action of a few matrix operations on these configuration states. Thus, the EPG method allows for fast and precise quantitation of echo intensities even if several gradients and RF pulses are applied. EPG diagrams aid in the comprehension of different types of echoes and their corresponding echo time. Despite its several benefits in regard to a large number of problems and issues, researchers and users still often refrain from applying EPGs. It seems that "phase graphing" is still seen as a kind of "magic." The present review investigates the foundation of EPGs and sheds light on prerequisites for adding more advanced phenomena such as diffusion. The links between diagrams and calculations are discussed. A further focus is on limitations and simplifications as well recent extensions within the EPG concept. To make the review complete, representative software for EPG coding is provided. © 2014 Wiley Periodicals, Inc.

Rickli A.,University of Basel | Hoener M.C.,Hoffmann-La Roche | Liechti M.E.,University of Basel
European Neuropsychopharmacology | Year: 2015

The pharmacology of novel psychoactive substances is mostly unknown. We evaluated the transporter and receptor interaction profiles of a series of para-(4)-substituted amphetamines and pyrovalerone cathinones. We tested the potency of these compounds to inhibit the norepinephrine (NE), dopamine (DA), and serotonin (5-HT) transporters (NET, DAT, and SERT, respectively) using human embryonic kidney 293 cells that express the respective human transporters. We also tested the substance-induced efflux of NE, DA, and 5-HT from monoamine-loaded cells, binding affinities to monoamine receptors, and 5-HT2B receptor activation. Para-(4)-substituted amphetamines, including 4-methylmethcathinone (mephedrone), 4-ethylmethcathinone, 4-fluoroamphetamine, 4-fluoromethamphetamine, 4-fluoromethcatinone (flephedrone), and 4-bromomethcathinone, were relatively more serotonergic (lower DAT:SERT ratio) compared with their analogs amphetamine, methamphetamine, and methcathinone. The 4-methyl, 4-ethyl, and 4-bromo groups resulted in enhanced serotonergic properties compared with the 4-fluoro group. The para-substituted amphetamines released NE and DA. 4-Fluoramphetamine, 4-flouromethamphetamine, 4-methylmethcathinone, and 4-ethylmethcathinone also released 5-HT similarly to 3,4-methylenedioxymethamphetamine. The pyrovalerone cathinones 3,4-methylenedioxypyrovalerone, pyrovalerone, α-pyrrolidinovalerophenone, 3,4-methylenedioxy-α-pyrrolidinopropiophenone, and 3,4-methylenedioxy-α-pyrrolidinobutiophenone potently inhibited the NET and DAT but not the SERT. Naphyrone was the only pyrovalerone that also inhibited the SERT. The pyrovalerone cathinones did not release monoamines. Most of the para-substituted amphetamines exhibited affinity for the 5-HT2A receptor but no relevant activation of the 5-HT2B receptor. All the cathinones exhibited reduced trace amine-associated receptor 1 binding compared with the non-β-keto-amphetamines. In conclusion, para-substituted amphetamines exhibited enhanced direct and indirect serotonergic agonist properties and are likely associated with more MDMA-like effects. The pharmacological profile of the pyrovalerone cathinones predicts pronounced stimulant effects and high abuse liability. © 2015 Elsevier B.V. and ECNP.

Heinlein M.,University of Strasbourg | Heinlein M.,University of Basel
Virology | Year: 2015

Replication and intercellular spread of viruses depend on host mechanisms supporting the formation, transport and turnover of functional complexes between viral genomes, virus-encoded products and cellular factors. To enhance these processes, viruses assemble and replicate in membrane-associated complexes that may develop into "virus factories" or "viroplasms" in which viral components and host factors required for replication are concentrated. Many plant viruses replicate in association with the cortical ER-actin network that is continuous between cells through plasmodesmata. The replication complexes can be highly organized and supported by network interactions between the viral genome and the virus-encoded proteins. Intracellular PD targeting of replication complexes links the process of movement to replication and provides specificity for transport of the viral genome by the virus-encoded movement proteins. The formation and trafficking of replication complexes and also the development and anchorage of replication factories involves important roles of the cortical cytoskeleton and associated motor proteins. © 2015 Elsevier Inc.

Steiner S.,University of Basel | Lori C.,University of Basel | Boehm A.,University of Marburg | Jenal U.,University of Basel
EMBO Journal | Year: 2013

In many bacterial pathogens, the second messenger c-di-GMP stimulates the production of an exopolysaccharide (EPS) matrix to shield bacteria from assaults of the immune system. How c-di-GMP induces EPS biogenesis is largely unknown. Here, we show that c-di-GMP allosterically activates the synthesis of poly-β-1,6-N-acetylglucosamine (poly-GlcNAc), a major extracellular matrix component of Escherichia coli biofilms. C-di-GMP binds directly to both PgaC and PgaD, the two inner membrane components of the poly-GlcNAc synthesis machinery to stimulate their glycosyltransferase activity. We demonstrate that the PgaCD machinery is a novel type c-di-GMP receptor, where ligand binding to two proteins stabilizes their interaction and promotes enzyme activity. This is the first example of a c-di-GMP-mediated process that relies on protein-protein interaction. At low c-di-GMP concentrations, PgaD fails to interact with PgaC and is rapidly degraded. Thus, when cells experience a c-di-GMP trough, PgaD turnover facilitates the irreversible inactivation of the Pga machinery, thereby temporarily uncoupling it from c-di-GMP signalling. These data uncover a mechanism of c-di-GMP-mediated EPS control and provide a frame for c-di-GMP signalling specificity in pathogenic bacteria. © 2013 European Molecular Biology Organization.

Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH-2007-2.4.1-6 | Award Amount: 4.18M | Year: 2008

From many perspectives our concept of the process of metastasis is inadequate and needs to be revised. In particular, the potential impact of recent ideas about the cellular basis of tumor growth (cancer stem cells) and the establishment by remote tumors of special permissive microenvironments in target organs prior to metastasis (metastatic niches) remains to be explored. In the TuMIC project we will use novel experimental approaches to integrate these newly emerging principles and ideas with the different hypotheses that have until now tried to explain the process of metastasis. Specifically we aim to understand how cancer stem cells behave in and contribute to metastasis, and how networks and pathways that are known to regulate metastasis affect their properties. Further objects are to determine how a permissive microenvironment for metastasis formation is established in given organs, how this contributes to determining patterns of metatasis, and how these microenvironments interact with cancer stem cells. These studies will facilitate the development of an improved and more accurate concept about the process of metastasis. In turn, this will have fundamental ramifications for the way in which novel anti-cancer therapies are designed, and most importantly should provide important new insights into how cancer and in particular metastatic disease can be successfully treated. With this in mind we will also perform preclinical studies that build on TuMIC findings with the aim of developing novel anti-cancer therapies.

Agency: Cordis | Branch: H2020 | Program: RIA | Phase: EURO-1-2014 | Award Amount: 2.29M | Year: 2015

The Eurozone crisis corroborated the warnings of economists that weak economic policy coordination and loose fiscal oversight would be insufficient to stabilise the monetary union. To prevent a recurrence of the crisis, economists, political actors and the Blueprint of the European Commission are asking for the construction of a deep and genuine economic and monetary union with reinforced governance architecture beyond the recently adopted mechanisms. Many models of a fiscal union have been proposed and discussed. What is missing are not ideas and economic analysis, but the political consensus among member states governments for a specific integration path. Therefore, this political science project analyses the politics of economic and fiscal integration, that is, the conflict structure among member states. To this end, we aim to study the preferences of member states governments for different models of a fiscal union. Our theoretical framework builds on the comparative political economy literature and liberal intergovernmentalism and argues that domestic economic, fiscal and political factors are the main determinants of member states preferences. To empirically study the extent to which governments preferences are shaped by these factors, we propose to conduct 165 semi-structured interviews with decision makers in all member states. The interview data will be analysed with a mixed-method strategy including quantitative analysis as well as case studies. We fully expect that the findings of the project will provide guidance for the successful implementation of a feasible reform of the governance architecture of the EU to the effective stabilisation of the economy. In addition to the political feasibility analysis, we aim to study the legal context of potential integration scenarios. The consortium conducting this research covers all regions of the EU and consists of 8 distinguished political scientists and one legal scholar.

Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH-2011.1.1-2 | Award Amount: 7.78M | Year: 2012

Individualisation of cancer therapy based on standardized biomarker assays is one of the most demanding challenges in cancer medicine. In the RESPONSIFY consortium, we will integrate information on response prediction from different breast cancer types and methodologies into biomarker tests for targeted therapies in the clinical routine setting. Those tests will be developed for commercialisation using the expertise of the involved SMEs and industrial partners. To reach this aim, we will use different genome based strategies to identify and characterise new biomarkers as well as validate biomarkers from previous projects. Genome based strategies include new molecular techniques such as genome wide next generation sequencing, epigenetics, gene and exon expression analysis, as well as kinome arrays, in-situ proteomics and quantitative PCR using FFPE tissue. A clearly defined marker finding-training-validation-approach will be the backbone of RESPONSIFY to reach a high level of evidence for commercial diagnostic tests. The established therapy stratification criteria will be further validated within clinical trials using the expertise of the clinical study groups. The clinical study group will develop a web-based data integration and processing system to standardise integration of clinical trial data and biomarker results in one system which will be further used for clinical biomarker driven trials. Health economic characteristics of combined testing and treatment strategies will be determined to inform decision makers, using state-of-the-art cost-utility analysis. Optimising the use of current therapy options and avoiding treatments patients will predictably not respond to, may improve cost-utility parameters to levels acceptable for most health systems. For rapid evaluation of response parameters, the major focus will be on neoadjuvant therapy. The RESPONSIFY project will lead to validated tests based on formalin-fixed paraffin embedded tissue to predict resistance

Agency: Cordis | Branch: FP7 | Program: CP-CSA-Infra | Phase: INFRA-2008-1.1.1 | Award Amount: 5.40M | Year: 2009

It is an unfortunate truth that the current electronics is facing a brick wall in a decade or so when Moores law has finally run its course and no further miniaturization is possible. We need something new. Coherent electron circuitry may provide that entirely new alternative. In nanocircuits the electrons can behave coherently over the circuit dimension and thus follow the rules of wave motion rather than Ohms law. To achieve coherence, however, electron scattering lengths must be larger than the sample size. That demands high purity to limit impurity scattering, but even limiting thermal scattering, by working at millikelvin temperature, we are still confined to circuits on the nanoscale. This provides the motivation for this application: there is an implicit imperative in nanoscience that there are enormous advantages to be gained at much lower temperatures. Despite the clear demand, nanoscience in general is inhibited from advancing beyond the millikelvin regime by a lack of appropriate expertise and facilities. However, in Europe we already have the greatest concentration of microkelvin infrastructure and espertise in the world, developed by our quantum-fluids community. By integration and rationalization MICROKELVIN aims to put this existing infrastructure at the disposal of the wider community and together develope new techniques and materials to bring corerent structures into the completely new regime. Our ultimate aim is the creation of a virtual European microkelvin laboratory without walls operating as a single entity. Integration will also allow us to pool our existing expertise and project it outword by greating new stand-alone machines able to access this temperature range anywhere. Such activity will also encourage European commercial interest in this opportunity. This advance is inevitable in the long term, but the European lead in the microkelvin field gives us the opportunity now to be the first with this new development. The infrastructure is there. The need is manifest. We simply have to bring the two together.

Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: KBBE-2007-2-2-06 | Award Amount: 3.92M | Year: 2008

Allergy has developed into a major health concern in Europe. Allergic diseases can currently be managed effectively but not cured. The onset of allergies stars early in life and there is increasing evidence that exogenous factors affecting the incidence of these illnesses exert their effect early in life, in part even prenatally. The highly interdisciplinary EFRAIM project will prospectively investigate the main protective factors in early life influencing the development of allergies in birth cohorts conducted in allergy protective environments in five European countries. These birth cohorts have been enrolling over 1,000 children and have collected detailed information on the onset of allergic illnesses, objective measures of allergies and a vast amount of information about a number of environmental exposures. Large biobanks with a variety of biological samples have been established. In the EFRAIM project particular attention will be given to the potential role of dietary exposures, lifestyle and other environmental (e.g. microbial) exposures early in life which are causal determinants rather than triggers of the illness. The mechanisms mediating these protective exposures such as the maturation of immune responses, gut colonisation, the mucosal barrier function and the genetic and epigenetic factors interacting with the environmental exposures will be investigated. The knowledge about protective exposures early in life can be turned into the development of preventive strategies. The EFRAIM project will actively address two routes of preventive interventions in animal models and in vitro studies: the development of an allergy protective milk formula and the development of an allergy vaccine. Both approaches are based on knowledge gained in the human studies. The EFRAIM project is expected to produce ground-breaking new insights on protective agents and their mechanisms that can be used to prevent the further development of allergies.

Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2013.2.2.1-2 | Award Amount: 9.24M | Year: 2013

Affective and non-affective psychoses have a major negative impact on human society. They account for 6.3% of the global burden of disease and cost 207 billion per year in Europe alone, making them the most expensive brain-related disorders and even more expensive than cardiovascular diseases. This socioeconomic burden is largely caused by two core disease features: onset in adolescence and early adulthood and long-term disabling disease courses. Both factors lead to enduring social and vocational exclusion and contribute to 8-20 times higher suicide rates in affected patients. Reliable and accessible prognostic tools will alleviate this burden by enabling individualised risk prediction, thus facilitating the targeted prevention of psychoses. Thus, we will first use routine brain imaging and complementary data to optimise our candidate biomarkers for the prediction and staging of psychoses and generate a prognostic system that generalises well across mental health services. Secondly, we will implement new multi-modal risk quantification tools to predict mental health-related disability in young help-seekers. The fusion of these tools with clinical knowledge will produce cybernetic prognostic services that accurately identify help-seekers at the highest risk of psychosis, poor functioning and suicide-related mortality. During this project we will secure our intellectual property rights and transform into a European company to commercially exploit these prognostic services through internet-based telemedicine applications. This will provide psychosis risk profiling tools to diverse target groups in the healthcare markets, including care-givers, the pharmaceutical industry and research institutions. By disseminating objective risk quantification, these products will provide firm diagnostic grounds for preventive therapy, improving outcomes and reducing costs. Thus, they will offer a unique selling proposition to the mental health sectors in Europe and beyond.

Agency: Cordis | Branch: FP7 | Program: MC-IIF | Phase: FP7-PEOPLE-2013-IIF | Award Amount: 269.74K | Year: 2014

The goal of this proposal is to develop a new strategy for asymmetric C(sp3)H activation using a chiral base instead of chiral ligand, and will focus on oxidative addition-induced and decarboxylation-induced reactions. Using this new strategy, a wide range of representative and valuable chiral four-membered (hetero)cyclic and five-membered (hetero)cyclic organic molecules will be synthesized. Typical chiral Brnsted acids and the designed ionic liquid-functionalized chiral phosphoric acids will be prepared by using commercially available raw materials. They will be tested in the two proposed concepts. In the case of oxidative addition-induced reactions, some feasible examples aiming at synthesizing chiral indanes, indolines, dihydrobenzofurans, benzocyclobutenes, and lactams will be developed from readily available aryl or alkenyl halides or triflates. For the decarboxylation-induced reactions, a racemic version will be first developed. Then, the chiral base concept will be applied in the synthesis of chiral benzocyclobutenes, indanes, indolines, and dihydrobenzofurans. In each of the reactions involved, some key reaction parameters including chiral acid, ligand, solvent, base, reaction temperature as well as the structural features of the substrates will be studied. In addition, recyclable ionic liquid-functionalized chiral Brnsted acids and the effect of traditional ionic liquids as the additives or solvents will be first studied in enantioselective C(sp3)H bond activation. In order to get a clear understanding on the nature of the asymmetric induction during the catalytic cycle, computational studies will also be performed using DFT methods. The applicants previous research experience in CH activation, ionic liquids catalysis and asymmetric catalysis areas will benefit the project. The project will foster mutually beneficial research collaboration in Europe in the field of CH activation and green chemistry.

Agency: Cordis | Branch: FP7 | Program: CSA-CA | Phase: SiS-2007- | Award Amount: 666.09K | Year: 2008

Childrens university is the most radical opening towards the general public that universities can undertake. If scientists provide lectures for children and children conquer auditories and laboratories, stereotyped images of science and scientists are knocked on the head immediately. New attractive and fascinating images of science and scientists appear. The first Childrens university in Germanys Tbingen (2002), constituted a new format of science awareness activities, awarded with Descartes Prize for Science Communication. The successful idea of Childrens universities spread out. Up to now 100 Childrens Universities filled 1.000.000 places with children aged from 7 to 12 years. But a European wide network does not exist and most of the Childrens Universities are situated in German speaking countries. Each of the 100 Childrens universities works solitary, as a single player and with a strong regional focus. Guidelines and quality criteria of established Childrens Universities does not exist. Some selective efficiency analyses let us assume, that children change their mind on science sustainably, but an overview of research result is missing. EUCUNET (European Childrens University Network) will coordinate a network of Childrens Universities preparing a knowledge base for present and future Childrens Universities Providers in order to professionalize the Childrens Universities movement. In conferences, through managed Development and Consultant Partnerships and on the community web portal a sustainable network should be established with the aim of knowledge sharing and capacity building. EUCUNET enables the European wide dissemination of the idea of Childrens university, invites stakeholders from different fields to develop the idea (especially policy maker) and helps establishing new Childrens universities. Hence more Children have the chance to participate in Childrens universities and set fire to the fascination of science.

Agency: Cordis | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-ITN-2008 | Award Amount: 3.32M | Year: 2009

The Post-genomic era calls for a deep understanding of protein structure and function. The elucidation of protein structures, localization, post-translation modifications, and protein-macromolecule interactions are important to establish their role in the biology of the cell. To establish their role and investigate the protein functions requires the integration of various complementary disciplines. Among all disciplines, chemistry is central in establishing new effective ways to manipulate a biological entity to understand cellular processes with molecular precision. For studying, analyzing and manipulating a macromolecule, the site-specific incorporation of reporter molecules, by virtue of ligation reactions, is a key factor. The BioChemLig research project presented herein describes novel approaches for the discovery of new bio-compatible and chemo-specific ligation reactions. The aim of this project is to develop new ligation processes with high efficiency, large scope of application, high chemoselectivity and high rates. Through a well established network, with demonstrated success (IBAAC Project: FP6-505020), we propose to focus our efforts in a highly combined and integrated training research action conducting research and using: unusual organic chemical functionalities for ligation, environmentally benign on water ligation reactions, specific 18F radiolabelled reagents, dendrimers conjugation methodologies, high-throughput screening for bond forming reactions, bio-chemo informatics platform for theoretical investigations, artificial metalo-enzymes for template-directed ligation, templated ligation reactions and HTS. This high quality integrated research should ultimately allow scientists to dissect cellular processes with molecular precision, speed up preparation of library of bioconjugates and deliver innovatives approaches to chemical biology.

News Article | November 1, 2016

It is a well-known fact that fitness and well-being go hand in hand. But being in good shape also protects against the health problems that arise when we feel particularly stressed at work. As reported by sports scientists from the University of Basel in Switzerland and colleagues from Sweden, it therefore pays to stay physically active, especially during periods of high stress. Psychosocial stress is one of the key factors leading to illness-related absences from work. This type of stress is accompanied by impaired mental well-being and an increase in depressive symptoms. It also raises the likelihood of cardiovascular risk factors such as high blood pressure and an unfavorable blood lipid profile. Conversely, a high fitness level is associated with fewer depressive symptoms and fewer cardiovascular risk factors. The data from the study published in the US journal Medicine and Science in Sports and Exercise shows that a high fitness level offers particularly effective protection for professionals who experience a high degree of stress in the workplace. To obtain this data, the researchers recorded the fitness levels of almost 200 Swedish employees - 51% men, mean age 39 years - using a so-called bicycle ergometer test. In addition, they measured various known cardiovascular risk factors such as blood pressure, body mass index, cholesterol, triglycerides and glycated hemoglobin. The participants were then asked to provide information on their current perception of stress. As expected, the study conducted by the Department of Sport, Exercise and Health at the University of Basel, the Institute of Stress Medicine, and Sahlgrenska University Hospital in Gothenburg illustrates that stressed individuals exhibit higher values of most cardiovascular risk factors. Furthermore, it was confirmed that cardiovascular fitness is linked to virtually all risk factors, with the risk factors being less high in people who are physically fit. The researchers demonstrated for the first time that the relationship between the subjective perception of stress and cardiovascular risk factors is moderated, so to speak, by fitness. In other words, among the stressed employees, there were particularly large differences between individuals with a high, medium, and low fitness level. For example, when stress levels were high, the LDL cholesterol values exceeded the clinically relevant limit in employees with a low fitness level - but not in those with a high fitness level. By contrast, where the exposure to stress was low, far smaller differences were observed between fitness levels. "Above all, these findings are significant because it is precisely when people are stressed that they tend to engage in physical activity less often," says Professor Markus Gerber of the University of Basel. Furthermore, he says that the study has direct implications for the therapy and treatment of stress-related disorders. To promote a physically active lifestyle, a high priority should be attached to the systematic measurement of cardiorespiratory fitness and the provision of theoretically sound and evidence-based physical activity counseling. Markus Gerber, Mats Börjesson, Thomas Ljung, Magnus Lindwall, and Ingibjörg H. Jonsdottir Fitness moderates the relationship between stress and cardiovascular risk factors Medicine & Science in Sports & Exercise (2016), doi: 10.1249/MSS.0000000000001005

News Article | November 10, 2015

Researchers at the Biozentrum of the University of Basel have developed a new technique using nanobodies. Employing the so-called “Morphotrap”, the distribution of the morphogen Dpp, which plays an important role in wing development, could be selectively manipulated and analyzed for the first time in the fruit fly. In the future, this tool may be applied for many further investigations of organ growth. The results of the study have been published in the current issue of Nature. The two basic processes that control organ development are the regulation of growth and of the spatial pattern. The research group of Professor Markus Affolter at the Biozentrum, University of Basel, has now developed a method named “Morphotrap” to study wing development in the fruit fly. Their results demonstrate that the signaling molecule Dpp, a so-called morphogen, influences growth in the center of the wing imaginal disc but not in the peripheral regions. It is the first time that an anti-GFP nanobody has been successfully employed in such an investigation. This tool also holds promise for future studies on organ development. Nanobodies are small antibody fragments derived from camels. They enable the research team of Markus Affolter to manipulate molecules in the living organism. The so-called “Morphotrap” method employs anti-GFP nanobodies. Using these Nanobodies, the functions of GFP-tagged proteins in living organisms can be studied faster and more effectively than by conventional methods. “These anti-GFP nanobodies inhibit the dispersal of the morphogen Dpp at different locations in the wing. Therefore they allow us to identify the influence of Dpp spreading on wing growth,” explains Stefan Harmansa, the first author of the study. To determine the influence of the morphogen Decapentaplegic (Dpp) in more detail, the Affolter group examined the wing disc of the fruit fly, called the imaginal disc. This is the precursor tissue of the wing of the adult fly and serves as a model for studies on organ development. “Our findings demonstrate that the morphogen Dpp only affects growth in the center of the imaginal disc. Growth continues in the periphery even when we fully block Dpp dispersal into this regions,” explains Harmansa. “Now, by employing anti GFP nanobodies, we have been able to show to which extent the morphogen Dpp determines the wing size and consequently we could disprove one of the two predominant theories in this field,” says Harmansa. The fact that anti GFP-nanobodies can successfully be applied for research in complex living organism is a great achievement. Affolter also plans to apply this technique in future research: “In a next step, we will investigate at what time in development Dpp acts to control central growth. The correlation between the spatial and temporal influence of Dpp will provide new insights into organ growth and may uncover possible causes of organ malformation,” says Affolter. Release Date: November 9, 2015 Source: University of Basel

News Article | November 10, 2016

Richard Tersoo Mnenga relives the life, times and fight of “JS Tarka” (published by Xlibris UK), a man who occupies a unique place in the history of regionalism and nationalism in Nigeria among Nigeria’s historical greats: Awolowo, Ahmadu Bello and Zik; while also in a class of his own. Joseph Sarwuan Tarka, the father of the Middle Belt politics, while he lived, pursued the good of his people in every way he could. His belief in political alliance and unity were central to the unity of the North and its political domination of that historic era. Unity was his religion, what he lived, fought and died for. He was a great man whose contributions to Nigeria’s development were remarkable. It would be an understatement to say that JS was the founder of the National Party of Nigeria and was able to bring all the minorities in Nigeria within the party. The entire Western Nigeria was won by UPN, the East by NPP, and the far North by PRP and GNPP. Shagari’s presidency was decided by the minorities in Nigeria because of Tarka. About the Author Comrade Richard Tersoo Mnenga was born in Adikpo, Kwande Local Government Area of Benue State where both his parents were teachers. After his primary education at Anendah Memorial Nursery and Primary School, he proceeded to the famous St. Andrews Secondary School Adikpo for his post primary education, and thereafter, went to the Bayero University Kano where he obtained his bachelor’s degree in political science. His quest for higher education took him to the University of Basel, Switzerland where he obtained a masters degree in Peace and Conflicts Transformation with flying colours. He started active national politics when he joined other patriotic Nigerians to participate in the activities of Campaign for Democracy CD, a pro – democracy group that fought military dictatorship in Nigeria. As a result of the courageous manner at which Alhaji M.D. Yusufu challenged the military self-succession bid by coming out to contest the presidency against General Sani Abacha, he championed a forum, Youth Solidarity for MD Yusufu where he was the National Coordinator. Following the return of democracy in Nigeria in 1999, Mnenga joined forces with like-minds to form the Concerned Nigeria Democratic Youth Forum and was made National President. The forum organized numerous seminars nationwide encouraging Nigerians to participate in the electioneering process in the face of apathy by many who doubted the sincerity due to their previous experiences. In 2012, the Universal Peace Federation in collaboration with Youth Federation for World Peace bestowed on him the ‘’Peace Ambassador’’ award. The Mbaiwen traditional council of Nanev in Kwande Local Government also turbaned him as the ‘’Onov Ikyundu U Mbaiwen’’ in 2016. He is currently a member of governing council, Federal University Otuoke, Bayelsa state and resides in Kaduna - Nigeria. Xlibris Publishing UK, an Author Solutions, LLC imprint, is a self-publishing services provider dedicated to serving authors throughout the United Kingdom. By focusing on the needs of creative writers and artists and adopting the latest print-on-demand publishing technology and strategies, we provide expert publishing services with direct and personal access to quality publication in hardcover, trade paperback, custom leather-bound and full-color formats. To date, Xlibris has helped to publish more than 60,000 titles. For more information, visit or call 0800 056 3182 to receive a free publishing guide. Follow us @XlibrisUK on Twitter for the latest news. ###

News Article | November 1, 2016

It is a well-known fact that fitness and well-being go hand in hand. But being in good shape also protects against the health problems that arise when we feel particularly stressed at work. As reported by sports scientists from the University of Basel and colleagues from Sweden, it therefore pays to stay physically active, especially during periods of high stress. Psychosocial stress is one of the key factors leading to illness-related absences from work. This type of stress is accompanied by impaired mental well-being and an increase in depressive symptoms. It also raises the likelihood of cardiovascular risk factors such as high blood pressure and an unfavorable blood lipid profile. Conversely, a high fitness level is associated with fewer depressive symptoms and fewer cardiovascular risk factors. The data from the study published in the US journal Medicine and Science in Sports and Exercise shows that a high fitness level offers particularly effective protection for professionals who experience a high degree of stress in the workplace. To obtain this data, the researchers recorded the fitness levels of almost 200 Swedish employees -- 51% men, mean age 39 years -- using a so-called bicycle ergometer test. In addition, they measured various known cardiovascular risk factors such as blood pressure, body mass index, cholesterol, triglycerides and glycated hemoglobin. The participants were then asked to provide information on their current perception of stress. As expected, the study conducted by the Department of Sport, Exercise and Health at the University of Basel, the Institute of Stress Medicine, and Sahlgrenska University Hospital in Gothenburg illustrates that stressed individuals exhibit higher values of most cardiovascular risk factors. Furthermore, it was confirmed that cardiovascular fitness is linked to virtually all risk factors, with the risk factors being less high in people who are physically fit. The researchers demonstrated for the first time that the relationship between the subjective perception of stress and cardiovascular risk factors is moderated, so to speak, by fitness. In other words, among the stressed employees, there were particularly large differences between individuals with a high, medium, and low fitness level. For example, when stress levels were high, the LDL cholesterol values exceeded the clinically relevant limit in employees with a low fitness level -- but not in those with a high fitness level. By contrast, where the exposure to stress was low, far smaller differences were observed between fitness levels. "Above all, these findings are significant because it is precisely when people are stressed that they tend to engage in physical activity less often," says Professor Markus Gerber of the University of Basel. Furthermore, he says that the study has direct implications for the therapy and treatment of stress-related disorders. To promote a physically active lifestyle, a high priority should be attached to the systematic measurement of cardiorespiratory fitness and the provision of theoretically sound and evidence-based physical activity counseling.

News Article | April 13, 2016

In cancer research, no success is more revered than the huge reduction in deaths from childhood leukaemia. From the 1960s to the 2000s, researchers boosted the number of children who survived acute lymphoblastic leukaemia from roughly 1 in 10 to around 9 in 10. What is sometimes overlooked, however, is that these dramatic gains against the most common form of childhood cancer were made not through the invention of new drugs or technologies, but rather through a reassessment of the tools in hand: a dogged analysis of the relative gains from different medicines and careful strategizing over how best to apply them side by side as combination therapies. “It wasn't just about pounding drugs together,” says Jedd Wolchok, a medical oncologist at Memorial Sloan Kettering Cancer Center in New York City. “It was about understanding the mechanism and figuring out what should be given when.” That lesson has particular relevance in cancer research today. A new class of immunotherapies — which turn the body's immune system against cancerous cells — is elevating hopes about combination therapies again. The drugs, called checkpoint inhibitors, have already generated great excitement in medicine when applied on their own. Now there are scores of trials mixing these immune-boosting drugs with one another, with radiation, with chemotherapies, with cancer-fighting viruses, with cell treatments and more. “The field is exploding,” says Crystal Mackall, who leads the paediatric cancer immunotherapy programme at Stanford University in California. Fast-moving trends in cancer biology often fail to meet expectations, and little is yet known about how these drugs work together. Some observers warn that the combinations being tested are simply marriages of convenience — making use of readily available compounds or capitalizing on business alliances. “In many cases, we're moving forward without a rationale,” says Alfred Zippelius, an oncologist at the University of Basel in Switzerland. “I suspect we'll see some disappointment in the next few years with respect to immunotherapy.” But many clinicians argue that delay is not an option as their patients queue up for the next available clinical trial. “Right now I have more patients that could benefit from combinations than there are combinations being tested,” says Antoni Ribas, an oncologist at the University of California, Los Angeles. “We're always waiting on the next slot.” Immunotherapies have been more than a century in the making, starting when physicians first noticed mysterious remissions in a few people with cancer who contracted a bacterial infection. The observations led to a hypothesis: perhaps the immune system is able to kill tumours when made hypervigilant by an infection. The concept has vast appeal. What better way to beat a fast-evolving biological system such as a tumour than with a fast-evolving biological immune system? But it took decades for researchers to turn that observation into something useful. Part of the trouble, they eventually learned, is that tumours suppress the immune response. T cells, the immune system's weapon of choice against cancer, would sometimes gather at the edge of a tumour and then just stop. It turned out that a class of molecules called inhibitory checkpoint proteins was holding those T cells at bay. These proteins normally protect the human body from unwarranted attack and autoimmunity, but they were also limiting the immune system's ability to detect and fight tumours. In 1996, immunologist James Allison, now at the University of Texas MD Anderson Cancer Center in Houston, showed that switching off a checkpoint protein called CTLA-4 helped mice to fend off tumours1. The discovery suggested that there was a way to re-mobilize T cells and beat cancer. In 2011, the US Food and Drug Administration (FDA) approved the first checkpoint inhibitor — a drug, called ipilimumab, that inhibits CTLA-4 — to treat advanced melanoma. The improvements were modest: about 20% of patients benefited from ipilimumab, and the survival gain was less than four months on average2. But a handful of recipients are still alive a decade after starting the therapy — a stark contrast with most new cancer drugs, which often benefit more patients in the short term, but don't have a durable response (see 'Desperately seeking survival'). Ipilimumab was at the leading edge of a flood of checkpoint inhibitors to enter clinical trials. The drug's developer, Bristol-Myers Squibb of New York, followed up with the approval of nivolumab, which inhibits the protein PD-1. And a host of other companies have jumped into the immunotherapy fray, as have academics such as Edward Garon at the University of California, Los Angeles. “Our group gladly shifted into this,” says Garon, who began focusing on checkpoint inhibitors in 2012. “It was very clear this was going to have a major impact.” But even as the family of checkpoint inhibitors was rapidly expanding, the drugs were running up against the same frustrating wall: only a minority of patients experienced long-lasting remission. And some cancers — such as prostate and pancreatic — responded poorly, if at all, to the drugs. Further research revealed a possible explanation: many people who were not responding well to the drugs were starting the treatment without that phalanx of T cells waiting at the margins of their tumours. (In the lingo of the field, their tumours were not inflamed.) Researchers reasoned that if they could raise this T-cell response first, and recruit the cells to the edges of the tumour, they might get a better result with the checkpoint inhibitors. That realization fuelled a rush to test combinations of drugs (see 'Combinatorial explosion'). Radiation and some chemotherapies kill enough tumour cells to release proteins that the immune system might then recognize as foreign and attack. Vaccines containing these proteins, called antigens, could have a similar effect. “On some level, one can make an argument for almost any drug combining well with an immunotherapy,” says Garon. “And obviously we know not all of them will.” One of the first combinations to be tested was made up of two immunotherapies — ipilimumab and nivolumab — at once. Although the targets of these drugs both do the same job, silencing T cells, they do so in different ways: CTLA-4 prevents the activation of T cells; PD-1 blocks the cells once they have infiltrated the tumour and its environment. And treating mice with compounds that block both proteins yielded a more-inflamed tumour as well3. “There was reason to think that if you block both, the T cells will be even more ready to kill the tumours,” says Michael Postow, an oncologist at Memorial Sloan Kettering. Together, ipilimumab and nivolumab boost response rates in people with advanced melanoma from 19% with just ipilimumab to 58% with the combination4. The combination also produces more-dangerous side effects than using either drug alone, but physicians are learning how to treat immunotherapy reactions, says Postow. Ipilimumab generally doesn't help people with lung cancer when given on its own, but researchers are now testing it with nivolumab. Normally, they would not have bothered to investigate a combination involving a drug that had failed on its own, Garon says. The new approach is grounded in immunology, but some researchers worry that the effort could be wasted, he adds. Researchers are also testing inhibitors of other checkpoint proteins, including TIM-3 and LAG-3, in combination with those that block PD-1. The combination approach is breathing life into drugs that had been shelved. For example, a protein called CD40 stimulates immune responses and has shown promise against cancer in animals. But in the wake of disappointing early clinical trials, some companies put their CD40 drugs to the side. Years later, mouse studies showed that combining CD40 drugs with a checkpoint inhibitor could boost their effect. Now, at least seven companies are developing them. Cancer immunologists have listed the protein as one of the targets they are most interested in studying, says Mac Cheever, a cancer immunologist at the Fred Hutchinson Cancer Research Center in Seattle, Washington. Cancer vaccines — long pursued by researchers but burdened by repeated failures in clinical trials — may also see a renaissance. There are now more than two dozen trials of cancer vaccines that make use of a checkpoint inhibitor. Some promising combinations have been uncovered by serendipitous clinical observations. Researchers at Johns Hopkins University in Baltimore, Maryland, were conducting trials of epigenetic drugs, which alter the chemical tags on chromosomes. They shifted a handful of people with lung cancer who had not responded to the drugs to a clinical trial of nivolumab. Five of them responded — a much higher proportion than expected. The discovery became the seed for an ongoing clinical trial launched in 2013 to study combinations of epigenetic drugs and immunotherapies. Preclinical work has now provided evidence that epigenetic drugs can affect aspects of the immune response. These chance observations could lead to real advances, says Wolchok. “We're riding the wave of enthusiasm.” But extracting the most from these combinations will require more well-designed preclinical studies to support the human ones. Just as attention to combinations of chemotherapies fuelled advances in treating paediatric leukaemias, the current combinatorial craze will require careful planning to work out the right pairings and timing of therapies. Another class of drug, known as targeted therapies, could also receive a significant boost from immunotherapy. These drugs, which target proteins bearing specific mutations, generate a high response rate when given to patients with those mutations, but the tumours often develop resistance to the drugs and come roaring back. Coupling targeted therapies with a checkpoint inhibitor, researchers reason, could yield both high response rates and durable remissions. One of the first targeted therapies for melanoma was an inhibitor that is specific to certain mutations in BRAF proteins that can drive tumour growth. However, an early attempt to combine this drug with ipilimumab was aborted when trial participants showed signs of possible liver damage5. No one was injured, but for some it was an important reminder that combinations can yield unanticipated side effects. “It was a good lesson for us to learn,” says Wolchok. “It will not be as simple as we imagined.” Paying careful attention to sample collection during clinical trials would help researchers to catch toxicity problems early, says Jennifer Wargo, a cancer researcher at MD Anderson. “We're making mistakes by looking just at clinical endpoints,” she adds. “We need to be smarter about how we run these trials.” In one of his latest trials, Wolchok wants to combine immunotherapy with a drug that targets a cellular pathway that some cancer cells use to maintain their rapid division. Cancers with mutations in this pathway, which is regulated by the protein MEK, can be extraordinarily difficult to treat. But the pathway is also important for T-cell development, so Wolchok is working to determine the right timing for the treatment. One approach could be to use a MEK inhibitor to quiet tumours in mice and to release tumour antigens. He would then wait for the T-cell response to rejuvenate before adding the immunotherapy. “You want to make sure you're not trying to activate the immune system at the same time you're turning off that signalling,” he says. Garon is watching such trials with optimism, but he's aware that there may be a limit to how well combinations will perform. He sees a cautionary tale in a drug from an earlier era that works mainly in people with a mutation in the protein EGFR. Researchers spent a decade trying to find drugs that could turn a non-responding patient into a responder. “It is now clear that there probably is no such agent,” he says. “I'm hopeful we won't be repeating that same response, but we have to watch our data cautiously.” Researchers are so ravenous for those data that the results are being unveiled at major meetings at an earlier stage than in the past, he adds. “People are getting up and presenting response rates when the number treated is five,” Garon says. “We generally have had a higher threshold than that.” He worries that presenting such early data could prompt community physicians in the audience to start making decisions on treatments before they are appropriately studied. The excitement is also fuelling a frenzy of clinical trials that are often based on speed rather than rationale. “Right now I'm kidding myself if I say I'm picking a combination because I have a scientific reason to pick it,” says Mackall. “It's likely to just be what was available.” The strategy may still produce some wins. “There is plenty of opportunity for serendipity now,” says Robert Vonderheide, who studies CD40 at the University of Pennsylvania in Philadelphia. But as the field matures, he says, this could give way to a more-systematic approach, similar to the careful planning and testing of variables used for paediatric leukaemias. Despite his concerns, Garon is excited to be a part of the immunotherapy wave. Last autumn, he and his colleagues held a banquet for the patients who had been enrolled in his first immunotherapy trials three years earlier. These were the lucky survivors — the few who had shown a dramatic response. As he looked around the table at the guests of honour, he marvelled at their recovery. All had been diagnosed with advanced lung cancer, and many had been too weak to work. Now they were talking about their families, re-embarking on careers and taking up old hobbies such as golf and running. “We've never been able to hold a banquet like that before,” he says. “I would love to hold many more.”

News Article | November 15, 2016

Crucial immune system proteins that make it harder for viruses to replicate might also help the attackers avoid detection, three new studies suggest. When faced with certain viruses, the proteins can set off a cascade of cell-to-cell messages that destroy antibody-producing immune cells. With those virus-fighting cells depleted, it’s easier for the invader to persist inside the host’s body. The finding begins to explain a longstanding conundrum: how certain chronic viral infections can dodge the immune system’s antibody response, says David Brooks, an immunologist at the University of Toronto not involved in the research. The new studies, all published October 21 in Science Immunology, pin the blame on the same set of proteins: type 1 interferons. Normally, type 1 interferons protect the body from viral siege. They snap into action when a virus infects cells, helping to activate other parts of the immune system. And they make cells less hospitable to viruses so that the foreign invaders can’t replicate as easily. But in three separate studies, scientists tracked mice’s immune response when infected with lymphocytic choriomeningitis virus, or LCMV. In each case, type 1 interferon proteins masterminded the loss of B cells, which produce antibodies specific to the virus that is being fought. Normally, those antibodies latch on to the target virus, flagging it for destruction by other immune cells called T cells. With fewer B cells, the virus can evade capture for longer. The proteins’ response “is driving the immune system to do something bad to itself,” says Dorian McGavern, an immunologist at the National Institute of Neurological Disorders and Stroke in Bethesda, Md., who led one of the studies. The interferon proteins didn’t directly destroy the B cells; they worked through middlemen instead. These intermediaries differed depending on factors including the site of infection and how much of the virus the mice received. T cells were one intermediary. McGavern and his colleagues filmed T cells actively destroying their B cell compatriots under the direction of the interferon proteins. When the scientists deleted those T cells, the B cells didn’t die off even though the interferons were still hanging around. Another study found that the interferons were sending messages not just through T cells, but via a cadre of other immune cells, too. Those messages told B cells to morph into cells that rapidly produce antibodies for the virus. But those cells die off within a few days instead of mounting a longer-term defense. That strategy could be helpful for a short-term infection, but less successful against a chronic one, says Daniel Pinschewer, a virologist at the University of Basel in Switzerland who led that study. Throwing the entire defense arsenal at the virus all at once leaves the immune system shorthanded later on. But interferon activity could prolong even short-term viral infections, a third study showed. There, scientists injected lower doses of LCMV into mice’s footpads and used high-powered microscopes to watch the infection play out in the lymph nodes. In this case, the interferon stifled B cells by working through inflammatory monocytes, white blood cells that rush to infection sites. “The net effect is beneficial for the virus,” says Matteo Iannacone, an immunologist at San Raffaele Scientific Institute in Milan who led the third study. Sticking around even a few days longer gives the virus more time to spread to new hosts. Since all three studies looked at the same virus, it’s not yet clear whether the mechanism extends to other viral infections. That’s a target for future research, Iannacone says. But Brooks thinks it’s likely that other viruses that dampen antibody response (like HIV and hepatitis C) could also be exploiting type 1 interferons.

Sato K.,University of California at Los Angeles | Loss D.,University of Basel | Tserkovnyak Y.,University of California at Los Angeles
Physical Review Letters | Year: 2010

We theoretically study tunneling of Cooper pairs from a superconductor spanning a two-dimensional topological insulator strip into its helical edge states. The coherent low-energy electron-pair tunneling sets off positive current cross correlations along the edges, which reflect an interplay of two quantum-entanglement processes. Most importantly, superconducting spin pairing dictates a Cooper pair partitioning into the helical edge liquids, which transport electrons in opposite directions for opposite spin orientations. At the same time, Luttinger-liquid correlations fractionalize electrons injected at a given edge into counterpropagating charge pulses carrying definite fractions of the elementary electron charge. © 2010 The American Physical Society.

Tserkovnyak Y.,University of California at Los Angeles | Loss D.,University of Basel
Physical Review Letters | Year: 2012

We theoretically study the magnetization dynamics of a thin ferromagnetic film exchange coupled with a surface of a strong three-dimensional topological insulator. We focus on the role of electronic zero modes imprinted by domain walls (DWs) or other topological textures in the magnetic film. Thermodynamically reciprocal hydrodynamic equations of motion are derived for the DW responding to electronic spin torques, on the one hand, and fictitious electromotive forces in the electronic chiral mode fomented by the DW, on the other. An experimental realization illustrating this physics is proposed based on a ferromagnetic strip, which cuts the topological insulator surface into two gapless regions. In the presence of a ferromagnetic DW, a chiral mode transverse to the magnetic strip acts as a dissipative interconnect, which is itself a dynamic object that controls (and, inversely, responds to) the magnetization dynamics. © 2012 American Physical Society.

Sen S.,Tata Institute of Fundamental Research | Reichert H.,University of Basel | VijayRaghavan K.,Tata Institute of Fundamental Research
Open Biology | Year: 2013

The regional specialization of brain function has been well documented in the mouse and fruitfly. The expression of regulatory factors in specific regions of the brain during development suggests that they function to establish or maintain this specialization. Here, we focus on two such factors-the Drosophila cephalic gap genes empty spiracles (ems) and orthodenticle (otd), and their vertebrate homologues Emx1/2 and Otx1/2-and review novel insight into their multiple crucial roles in the formation of complex sensory systems. While the early requirement of these genes in specification of the neuroectoderm has been discussed previously, here we consider more recent studies that elucidate the later functions of these genes in sensory system formation in vertebrates and invertebrates. These new studies show that the ems and Emx genes in both flies and mice are essential for the development of the peripheral and central neurons of their respective olfactory systems. Moreover, they demonstrate that the otd and Otx genes in both flies and mice are essential for the development of the peripheral and central neurons of their respective visual systems. Based on these recent experimental findings, we discuss the possibility that the olfactory and visual systems of flies and mice share a common evolutionary origin, in that the conserved visual and olfactory circuit elements derive from conserved domains of otd/Otx and ems/Emx action in the urbilaterian ancestor. © 2013 The Authors.

Duneau D.,University of Basel | Duneau D.,Cornell University | Ebert D.,University of Basel
PLoS Biology | Year: 2012

In species with separate sexes, parasite prevalence and disease expression is often different between males and females. This effect has mainly been attributed to sex differences in host traits, such as immune response. Here, we make the case for how properties of the parasites themselves can also matter. Specifically, we suggest that differences between host sexes in many different traits, such as morphology and hormone levels, can impose selection on parasites. This selection can eventually lead to parasite adaptations specific to the host sex more commonly encountered, or to differential expression of parasite traits depending on which host sex they find themselves in. Parasites adapted to the sex of the host in this way can contribute to differences between males and females in disease prevalence and expression. Considering those possibilities can help shed light on host-parasite interactions, and impact epidemiological and medical science. © 2012 Duneau, Ebert.

Kudryashev M.,University of Basel | Wang R.Y.-R.,University of Washington | Brackmann M.,University of Basel | Scherer S.,University of Basel | And 6 more authors.
Cell | Year: 2015

Bacteria use rapid contraction of a long sheath of the type VI secretion system (T6SS) to deliver effectors into a target cell. Here, we present an atomic-resolution structure of a native contracted Vibrio cholerae sheath determined by cryo-electron microscopy. The sheath subunits, composed of tightly interacting proteins VipA and VipB, assemble into a six-start helix. The helix is stabilized by a core domain assembled from four β strands donated by one VipA and two VipB molecules. The fold of inner and middle layers is conserved between T6SS and phage sheaths. However, the structure of the outer layer is distinct and suggests a mechanism of interaction of the bacterial sheath with an accessory ATPase, ClpV, that facilitates multiple rounds of effector delivery. Our results provide a mechanistic insight into assembly of contractile nanomachines that bacteria and phages use to translocate macromolecules across membranes. © 2015 Elsevier Inc.

Aharonovich I.,University of Technology, Sydney | Neu E.,University of Basel
Advanced Optical Materials | Year: 2014

The burgeoning field of nanophotonics has grown to be a major research area, primarily because of the ability to control and manipulate single quantum systems (emitters) and single photons on demand. For many years, studying nanophotonic phenomena was limited to traditional semiconductors (including silicon and GaAs) and experiments were carried out predominantly at cryogenic temperatures. In the last decade, however, diamond has emerged as a new contender to study photonic phenomena at the nanoscale. Offering a plethora of quantum emitters that are optically active at room temperature and ambient conditions, diamond has been exploited to demonstrate super-resolution microscopy and realize entanglement, Purcell enhancement, and other quantum and classical nanophotonic effects. Elucidating the importance of diamond as a material, this progress report highlights the recent achievements in the field of diamond nanophotonics, and conveys a roadmap for future experiments and technological advancements. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Ramm S.A.,Bielefeld University | Scharer L.,University of Basel
Biological Reviews | Year: 2014

Larger testes are considered the quintessential adaptation to sperm competition. However, the strong focus on testis size in evolutionary research risks ignoring other potentially adaptive features of testicular function, many of which will also be shaped by post-mating sexual selection. Here we advocate a more integrated research programme that simultaneously takes into account the developmental machinery of spermatogenesis and the various selection pressures that act on this machinery and its products. The testis is a complex organ, and so we begin by outlining how we can think about the evolution of testicular function both in terms of the composition and spatial organisation of the testis ('testicular histology'), as well as in terms of the logical organisation of cell division during spermatogenesis ('testicular architecture'). We then apply these concepts to ask which aspects of testicular function we can expect to be shaped by post-mating sexual selection. We first assess the impact of selection on those traits most strongly associated with sperm competition, namely the number and kind of sperm produced. A broad range of studies now support our contention that post-mating sexual selection affects many aspects of testicular function besides gross testis size, for example, to maximise spermatogenic efficiency or to enable the production of particular sperm morphologies. We then broaden our focus to ask how testicular function is affected by fluctuation in sperm demand. Such fluctuation can occur over an individual's lifetime (for example due to seasonality in reproduction) and may select for particular types of testicular histology and architecture depending on the particular reproductive ecology of the species in question. Fluctuation in sperm demand also occurs over evolutionary time, due to shifts in the mating system, and this may have various consequences for testicular function, for example on rates of proliferation-induced mutation and for dealing with intragenomic conflict. We end by suggesting additional approaches that could be applied to study testicular function, and conclude that simultaneously considering the machinery, products and scheduling of spermatogenesis will be crucial as we seek to understand more fully the evolution of this most fundamental of male reproductive traits. © 2014 The Authors. Biological Reviews © 2014 Cambridge Philosophical Society.

Hofmann F.T.,Max Planck Institute of Molecular Physiology | Szostak J.W.,Massachusetts General Hospital | Seebeck F.P.,Max Planck Institute of Molecular Physiology | Seebeck F.P.,University of Basel
Journal of the American Chemical Society | Year: 2012

In this report we present a method to identify functional artificial lantipeptides. In vitro translation coupled with an enzyme-free protocol for posttranslational modification allows preparation of more than 10 11 different lanthionine containing peptides. This diversity can be searched for functional molecules using mRNA-lantipeptide display. We validated this approach by isolating binders toward Sortase A, a transamidase which is required for virulence of Staphylococcus aureus. The interaction of selected lantipeptides with Sortase A is highly dependent on the presence of a (2S,6R)-lanthionine in the peptide and an active conformation of the protein. © 2012 American Chemical Society.

Agency For Science and University of Basel | Date: 2014-10-17

The present invention relates to certain compounds (e.g., imidazopyrazine, imidazopyridine, imidazopyridazine and imidazpyrimidine compounds) that act as inhibitors of the MAP kinase interacting kinases MNK2a, MNK2b, MNK1a, and MNK1b. The present invention further relates to pharmaceutical compositions comprising these compounds, and to the use of the compounds for the preparation of a medicament for the prophylaxis and treatment of diseases (e.g., proliferative diseases (e.g., cancer), neurodegenerative diseases (e.g., Alzheimers disease), metabolic diseases (e.g. diabetes), neurodevelopmental disorders (e.g. autism), or psychiatric disorders (e.g. schizophrenia or anxiety)) as well as methods of treating these diseases.

Agency: Cordis | Branch: H2020 | Program: ERC-COG | Phase: ERC-CoG-2015 | Award Amount: 1.89M | Year: 2016

The project seeks to explore culinary practice among early farming European communities, from the Aegean to Central Europe, spanning the Neolithic through to the Iron Age (7th-1st millennia BC). The project seeks to identify the food cultures of prehistoric Europe, and to reconstruct how cultivated and wild plant foods were transformed into dishes exploring their underlying cultural and environmental contexts and their evolution through time. The project will explore how culinary identities were shaped through the selection of plant foods both in terms of ingredients as well as processing and cooking practices. Thus not only species and meals but also the equipment involved in plant food preparation will be considered for the study area, linking the end product to the relevant technologies of transformation. Macroscopic and microscopic examination of the archaeological finds and experimental replication of various aspects of food preparation techniques informed by ethnographic investigations will form the main analytical tools. The interdisciplinary and contextual examination of the archaeological record will provide a fresh insight into prehistoric cuisine in Europe, the transformation of nature to culture through cooking. The project will revolutionise perceptions of prehistoric food preparation providing insights for the longue dure of traditional plant foods constituting Europes intangible cultural heritage.

Agency: Cordis | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2015-ETN | Award Amount: 3.94M | Year: 2015

The ability of cells to polarize underlies the most basic biological functions such as motility and response to external challenges, but also the formation and maintenance of tissues in a multicellular organism. The importance of cell polarity is underscored by the fact that cell polarity is essential for animal development and is perturbed in disease states such as cancer. Understanding cell polarity requires knowledge of the molecular players involved and a quantitative description of their biochemical interactions, as well as the mechanical processes underlying polarity establishment. PolarNet brings together academic and private partners from 7 European countries to establish a multidisciplinary, intersectoral training and research programme that will study the basic principles of cell polarity. The research will combine complementary model systems ranging from fungi and cultured mammalian cells to whole organisms, and employ a broad set of approaches such as advanced genetics, protein biochemistry, high-resolution live imaging and image analysis, biophysics and theoretical modelling. This setting provides an opportunity to train early stage researchers in a unique combination of experimental and theoretical approaches. This will provide an excellent starting point for a successful career in the rapidly expanding field of multidisciplinary or integrative biology. Training Europes next generation of scientists at the forefront of cell and organismal polarity research is crucial for progress in several medically important fields, including cancer research and stem cell biology. The tight collaboration with non-academic partners will strengthen the technological base of different projects and provide early stage researchers with insights into the translation potential of the performed studies and the career development opportunities in biomedical industry.

Agency: Cordis | Branch: FP7 | Program: CP | Phase: ICT-2011.9.1 | Award Amount: 2.66M | Year: 2011

We propose to realize of a new class of interferometers based on entangled states of atomic Bose-Einstein condensates. These will have sensitivities beyond the shot-noise limit, potentially approaching the ultimate Heisenberg limit dictated by quantum mechanics. Our goal is to achieve an optimal control of the entanglement by means of novel experimental and theoretical tools to fully exploit its capabilities in precision measurements of time, forces and accelerations. A successful completion of this project will disclose a new generation of quantum-enhanced sensors for applications and fundamental physics, and also lead to a better control and exploitation of quantum entanglement for ICT purposes.

Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: HEALTH.2010.1.4-1 | Award Amount: 15.80M | Year: 2010

Primary immune deficiencies (PID) are inherited disorders of the adaptive and innate immune system marked by severe infections, autoimmunity and high risk of cancer. Treatment entails hematopoietic stem cell (HSC) transplantation from allogeneic donors, however in the absence of an HLA compatible donor, HSCT outcome is limited by delayed or suboptimal reconstitution and complications. SCID-X1 and ADA-SCID have been successfully treated with autologous gene corrected HSC, however, associated with safety issues inherent to first generation retroviral vectors. This project utilizes genetically modified HSC and their descendants as immunotherapeutic cells to build a healthy immune system in PID patients, and is carried out by clinical centres, scientists and industrial partners pioneering in the field of advanced therapies and aiming at broad clinical application of safe cell-based therapeutic products. Multicentre phase I/II clinical trials for SCID-X1 and WAS are ready to start. Disease targeted technology to cure ADA-SCID, V(D)J recombination defects and CGD by gene corrected HSC and novel approaches in IPEX and HLH to gene modify already committed cells will be investigated. Based on rigorous preclinical efficacy and toxicology evaluation, flanked by basic studies aimed at improving HSC homing capacity and thymic epithelium regeneration, new clinical trials will be implemented. The consortium will establish a technology platform to implement, harmonize and run controlled, standardized multicentre preclinical studies using state-of-the-art advanced therapy. Strict observance of good practice quality guidelines and regulation of medicinal product development will be ensured. The successful completion of the project will be instrumental to accomplish and broaden clinical application of medicinal products able to rebuild and modulate the immune system with an anticipated impact that extends beyond PID to acquired immune disorders, allogeneic HSCT and cancer treatment.

News Article | April 7, 2016

Researchers of the University of Basel and Empa have gotten a step closer to engineering artificial muscles: they have developed a method to generate nanometer-thin silicone films. Elastomers, which can transform electrical energy into mechanical energy, have a wide variety of applications, i.e. powering windscreen wipers, sound generation, and operating camera lenses. By surrounding the synthetic material with electrodes and applying operation voltage, it expands laterally. In the field of medicine, this principle is promising for the development of artificial muscles for treating severe incontinence, as the consortium recently communicated. To provide the necessary strain, micrometer-thick silicone layers need an operation voltage of several hundred volts, which is by far too high for applications within the human body. In contrast, nanometer-thin layers require only a few volts. To generate forces necessary to reach continence, several thousand layers have to be put on top of each other. Current manufacturing methods do not allow the efficient fabrication of such layered nanostructures. The team of Professor Bert Müller from the Biomaterials Science Center of the University of Basel, together with researchers of Empa, has developed a deposition method to prepare extremely flat silicone layers that are much thinner than a micron. The roughness is smaller than one nanometer. For this purpose, silicone molecules in solution are sprayed assisted by high voltages — termed electrospray deposition. Usually electrospraying is based on direct current. The researchers from Basel, however, employ an alternating current. “This rather simple deposition technique has a huge potential, as it is adaptable to the industrial requirements for producing artificial muscles as well as powering windscreen wipers,” Müller says. He expects that patients suffering from severe incontinence could benefit from the technology.

News Article | November 28, 2016

Mental disorders and physical diseases frequently go hand in hand. For the first time, psychologists at the University of Basel and Ruhr University Bochum have identified temporal patterns in young people: arthritis and diseases of the digestive system are more common after depression, while anxiety disorders tend to be followed by skin diseases. Physical diseases and mental disorders affect a person's quality of life and present a huge challenge for the healthcare system. If physical and mental disorders systematically co-occur from an early age, there is a risk that the sick child or adolescent will suffer from untoward developments. In a project financed by the Swiss National Science Foundation, a research group led by PD Dr. Marion Tegethoff in collaboration with Professor Gunther Meinlschmidt from the University of Basel's Faculty of Psychology has now examined the temporal pattern and relationship between physical diseases and mental disorders in children and young people. In the journal PLOS ONE, they analyzed data from a representative sample of 6,483 teenagers from the US aged between 13 and 18. The researchers noted that some physical diseases tend to occur more frequently in children and adolescents if they have previously suffered from certain mental disorders. Likewise, certain mental disorders tend to occur more frequently after the onset of particular physical diseases. Affective disorders such as depression were frequently followed by arthritis and diseases of the digestive system, while the same relationship existed between anxiety disorders and skin diseases. Anxiety disorders were more common if the person had already suffered from heart disease. A close association was also established for the first time between epileptic disorders and subsequent eating disorders. The results offer important insights into the causal relationship between mental disorders and physical diseases. The newly identified temporal associations draw attention to processes that could be relevant both to the origins of physical diseases and mental disorders and to their treatment. In an earlier study, the same authors had already provided evidence for the relationship between mental disorders and physical diseases in young people. "For the first time, we have established that epilepsy is followed by an increased risk of eating disorders - a phenomenon, that had previously been described only in single case reports. This suggests that approaches to epilepsy treatment could also have potential in the context of eating disorders," explains Marion Tegethoff, the study's lead author. From a health policy perspective, the findings underscore that the treatment of mental disorders and physical diseases should be closely interlinked from an early age on. Marion Tegethoff, Esther Stalujanis, Angelo Belardi, Gunther Meinlschmidt Chronology of Onset of Mental Disorders and Physical Diseases in Mental-Physical Comorbidity - A National Representative Survey of Adolescents PLOS ONE (2016), doi: 10.1371/journal.pone.0165196

Physical diseases are often linked to mental disorders that enhance them. A new research found that arthritis and diseases of the digestive system are most common in people who have suffered from depression. The study also underlined that disorders from the anxiety spectrum are commonly associated with skin diseases. The research was conducted by researchers at the University of Basel and Ruhr University Bochum, and was published in the journal Plos One. The way psychological events and the manner people perceive them impacting our health has never been scientifically proven, although previous studies have shown correlation between the two. Until this study, there was no clear causality between these types of affections. Young people, who are still developing, are the most affected by these causality, as their psychological state of mind can trigger health issues, according to this research. The research analyzed the temporal patterns and the relationship between physical diseases and the mental ones, looking at a representative data sample of 6,483 teenagers from the United States, within the age interval of 13 to 18. As part of the research, the scientists observed that a series of physical diseases tend to take place more frequently in children and adolescents who have previously been affected by a series of mental disorders. Anxiety is more common when subjects suffered from a heart disease, and epileptic disorders can be linked to developing eating disorders. "For the first time, we have established that epilepsy is followed by an increased risk of eating disorders — a phenomenon, that had previously been described only in single case reports. This suggests that approaches to epilepsy treatment could also have potential in the context of eating disorders," noted Marion Tegethoff, the study's lead author. The results of this study are all the more important as they offer insight on the anatomy of physical diseases, as well as on the repercussions of some psychological and psychiatric affections. The research could help in finding a new series of treatments that could address the underlying causes of these disorders, thus avoiding these causalities in future young people. As part of the research, patients who had a skin condition called atopic dermatitis improved their physical condition after psychotherapy sessions, which suggests a correlation between the two types of manifestations. A significant part of the patients who experienced the skin disease had been suffering from anxiety, which was found to be a significant contributing factor to their physical condition. Other underlying mechanisms that consisted of psychological disorders could have triggered skin diseases, such as skin health-relevant immune alterations, including slowed wound healing and augmented induction of inflammatory processes and immunoglobulin production. A previous study led by the same research team proved that chronic physical diseases and mental disorders are correlated, occurring systematically in adults as well as teenagers. The study also connected depression with indigestion, after 35.3 percent of the children and adolescents reported at least a mental disorder and a chronic physical disease. "Future studies should identify risk factors as well as the biological and psychological mechanisms responsible for these associations, in order to develop interdisciplinary approaches," noted Tegethoff, who was also a lead author of that study. © 2017 Tech Times, All rights reserved. Do not reproduce without permission.

News Article | October 10, 2016

An analysis of the world's most valuable scientific documents and manuscripts, and it illustrates both how far science has come in a relatively short time, and how little we value our legacy in monetary terms Significance: Einstein's first scientific paper, written at 16 years of age (he is pictured above at 14), contains the seeds of the theory of relativity. It pursues an inquiry relating to the ether, the elastic substance which, according to the science of the day, filled all of space. It was Einstein's continued interest in questions on the boundary between mechanics and electro-magnetics that provided the departure point for his 1905 special theory of relativity, which was to cause the final abandonment of the ether concept. 49 - Journey of Discovery to Port Phillip, New South Wales by William Hovell and Hamilton Hume Significance: The only unpublished proof copy in private hands of a landmark book about the exploration of Australia. Look closely at the map above (from a Sotheby's auctioned copy of the second edition) and you'll see that Port Phillip is the area upon which Australia's second largest city, Melbourne, now sits. The auction copy was given to French navigator Louis de Freycinet (1779 – 1841), whose annotations to the text can be seen in the auction copy alongside those of its editor, convicted murderer and subsequently member of Parliament, Dr William Bland. Freycinet was the first person to publish a map showing the full coastline of Australia in 1811. The full text of the most expensive Australian book ever to sell at auction has been digitized and is available for free online via Project Gutenberg. 48 - The Principal Navigations, Voiages, Traffiques and Discoveries of the English Nation by Richard Hakluyt The Wright-Molyneux map is based on Mercator's projection, which Mercator expected would be a valuable tool to navigators, and this map was one of the first to use it. Unfortunately, Mercator gave no explanation as to the underlying mathematics used to create the map and it was left to Edward Wright to explain it in Certain Errors in Navigation Detected and Corrected (1599), hence the projection sometimes being called the Wright Projection by English mapmakers. The map is linked to Emery Molyneux, whose globe of 1592 provided most of the geographical information it contains. Hakluyt's use of this map in his publication was to show "so much of the world as hath beene hetherto discouered, and is comme to our knowledge." Wright later translated John Napier's pioneering 1614 work that introduced the idea of logarithms from Latin into English. From the auction description: One of the most important works of the 17th century, remarkable in its content and execution, being the work of one man – a gifted naturalist, an artist (trained as a portrait painter in France), a skilled cartographer and sympathetic ethnographer. Samuel de Champlain's account of his voyages of 1604, 1610, 1611 and 1613 are a key exploration narrative, one considerably enhanced by the author's lively illustrations in which he records his mapping of a vast area with unprecedented detail and accuracy, while also depicting the flora and fauna of the New World. The vignettes within the rare Carte Geographique de la Nouvelle Franse are an artist's rendition of new species, giving a hint of the varied and vast natural resources to be found in the New World. Of this monumental cartographic endeavor, Armstrong called the map, "not the work of a bureaucrat, but of a skillful pyschologist, promoter and politician…Champlain's map of 1612 is the most important historical cartography of Canada." Some perspective on price: Interestingly, several other items of historical significance to the United States have sold for a similar amount at auction. These include a 1777 manuscript map of New York Island from the American Revolutionary War (above) that fetched $782,500, the original autograph manuscript by Julia Ward Howe of "The Battle Hymn of the Republic" that also fetched $782,500, W.I. Stone's 1823 "50th Anniversary" engraving of the 'Declaration of Independence' that also sold for $782,500, and a draft manuscript of the United Kingdom's Stamp Act of 1765 (an effort to heavily tax the colonies and a catalyst for the American Revolution), that sold for $755,000. 46 - The Decades of the Newe Worlde by Pietro Martire d'Anghiera It is the first series of narratives on epic voyages voyages based on the first three Decades of Peter Martyr (Pietro Martire d'Anghiera – read the text in English here), which were originally written in Latin between 1511 and 1530. The book was edited and translated into English by Richard Eden and published in London by William Powell in 1555. The auctioned book sold for almost 10 times its estimate, mainly due to its significance as the first edition of the first collection of voyages printed in English, and the first work to contain narratives of English voyages. Besides the three Decades of Peter Martyre, it contains a translation of that author's "De nuper sub D. Carolo repertis Insulis" (describing the voyages of Francisco Hernández de Córdoba, Juan de Grijalva, and Hernán Cortés), the Bull of Pope Alexander (by which he decreed that the world was to be divided between Spain and Portugal), as well as translations of the most important parts of the works pertaining to the maritime discovery of the New World by Oviedo, Maximilian of Transylvania, Vespuccius, Gomara and others. In the book's preface, the colonization of North America by the English is advocated for the first time and according to The art of navigation in England in Elizabethan and early Stuart times, "for over a quarter of a century it proved to be the English source-book of geographical and navigational knowledge" and "as such it was to be of the utmost value to men like Hawkins and Drake." Emphasizing this last point is the book's provenance - this book was Roger North's copy. In 1617, North had sailed with Sir Walter Raleigh in his second expedition to Guiana in South America in search of the mythical "city of gold" known as El Dorado, and in 1620, North was a prime mover behind attempts to establish an English colony on the River Amazon delta. The book bears his signature on the title as well as his motto, "Durum Pati," believed to be an abbreviation of Horace's "Durum, sed levius fit patientia..." ('Tis hard! But that which we are not permitted to correct is rendered lighter by patience). The book is available in full on the Internet Archive. 45 - The Atlantic Neptune published for the use of the Royal Navy of Great Britain by Joseph Des Barres Significance: Swiss cartographer Joseph Frederick Wallet Des Barres (1722-1824) was a member of the famous Huguenot family who studied mathematics under Daniel Bernoulli at the University of Basel, then military surveying at Great Britain's Royal Military Academy, leading to a commission in 1756 into the Royal Americans and a role as a cartographer in the Seven Years' War. Using documents captured at Louisbourg, Des Barres compiled a large-scale chart of the St. Lawrence River and Gulf, which enabled the British Navy to navigate its warships to and take control of the French capital at Quebec. The victory demonstrated the benefits of accurate marine surveys, and Des Barres' capability in particular, resulting in the admiralty providing him with the resources to accurately chart the coast of Atlantic Canada, and the eastern seaboard from New England to the West Indies. This book resulted some 17 years later: a maritime atlas that set the standard for nautical charting for half a century. Significance: The first atlas to be so called. The first four parts had been published between 1585 and 1589 (see previous lot). To these were added a fifth and final part, Atlantis pars altera, published in 1595, a year after Mercator's death, and overseen by his son Rumold. This part includes maps of the world and the continents. The complete atlas was dedicated to Queen Elizabeth and the whole was preceded by the famous engraved general title-page showing Atlas measuring the world with a pair of dividers. Interestingly, Mercator refers to Atlas, King of Mauretania (now Morocco), a mathematician and philosopher who is generally credited with having made the first celestial globe, not the mythical Greek god Atlas, whose punishment was to carry the world and heavens on his shoulders. We humans certainly have a propensity to get our stories mixed up. Significance: The most expensive of numerous copies of John James Audubon's second masterpiece. "Viviparous" means birthing young from within the body, so this book is essentially a study of North American mammalian wildlife, and like Audubon's best known "Birds of America," each is superbly illustrated in its natural habitat. Equally as as impressive and sweeping as his ornithological work, the "Viviparous Quadrupeds of North America" is the result of the artist/naturalist's years of field research, travel, and seemingly endless study and is the outstanding work on American animals produced in the 19th-century. The entire book has been digitized by the University of Michigan's Special Collections Library and is available in high resolution for free download and use, with attribution.

News Article | August 22, 2016

Abstract: Physicists at the University of Basel have succeeded in watching a silver catalyst at work for the first time with the aid of an atomic force microscope. The observations made during an Ullmann reaction have allowed the researchers to calculate the energy turnover and, potentially, to optimize the catalysis. The study, which was performed with experts from Japan and Iran, has been published in the scientific journal Small. The Ullmann reaction examined is a chemical reaction in which silver atoms catalyze the bond between two carbon atoms to which iodine was previously bonded. Although scientists have known about this type of reaction since 1901 and used it for many important chemical conversions, it was not previously possible to observe the intermediate product of the reaction in detail. Using an atomic force microscope, the team of researchers led by Professor Ernst Meyer and Dr. Shigeki Kawai from the Swiss Nanoscience Institute and the Department of Physics at the University of Basel has now succeeded in displaying this reaction at atomic resolution. Surprisingly, it was revealed that the silver atoms react with the molecules at temperatures of around -120°C and seem to curve like a bridge over a river. In the second stage of the reaction, which requires the temperature to be increased to around 105°C and generates the end product, the silver atoms are freed again and two carbon atoms bond together. Calculating energy The Ullmann reaction has been used for chemical syntheses for a long time now. Interest in this linking of carbon atoms has recently increased again because it can be used to bind organic molecules to surfaces and produce solvent-free polymers. Detailed observations of how the catalysts work enable scientists to better understand the reaction process. Previous analyses failed to show the spatial arrangement of the organometallic intermediate product. The detailed images now obtained are the first to allow project partner Professor Stefan Goedecker (Department of Physics, University of Basel) to calculate the energy turnover of the Ullmann reaction examined. This data confirms the unusual spatial arrangement of the intermediate product and indicates how the reaction could be optimized. Relatively low temperatures The observed curving and flexibility of the molecules is probably the reason why the reaction requires relatively low temperatures of 105°C. The molecules are subject to mechanical tension and can therefore react more easily, that is at lower temperatures. If other catalysts could be used to generate intermediate products like these that are subject to tension, then catalytic reactions could also be possible at lower temperatures. This would make ecological and economic sense because traditional catalysts with platinum, rhodium, or palladium often require high operating temperatures of 500°C, which leads to the emission of waste gases in a cold state. ### The research work was the result of a collaboration between the Department of Physics at the University of Basel, the National Institute of Materials Science (Japan), the Japan Science and Technology Agency (Japan), the University of Tokyo (Japan), and Shadid Beheshti University (Iran). For more information, please click If you have a comment, please us. Issuers of news releases, not 7th Wave, Inc. or Nanotechnology Now, are solely responsible for the accuracy of the content.

News Article | March 14, 2016

Liposomes are currently used as drug delivery vehicles but recognized by the immune system. Scientists from the universities of Basel and Fribourg have shown that special artificial liposomes do not elicit any reaction in human and porcine sera as well as pigs. The study was published in the Journal Nanomedicine: Nanotechnology, Biology, and Medicine. Liposomes are soap-bubble-like nanocontainers made of a double phospholipid membrane that shields off an inner aqueous compartment. In a lenticular form, as developed by Professor Andreas Zumbühl's team at the Department of Chemistry at the University of Fribourg, they are promising candidates for drug delivery to constricted coronary arteries. Here, the blood flows through the stenosed artery segments with high velocity and is subjected to enhanced shear forces. Under these conditions, the liposomes open and release their content. Unfortunately, the immune system does recognize these liposomes as foreign bodies. The activation of the immune system may lead to a pseudo-allergy. Earlier studies have shown that negative effects are found in up to 30 percent of the cases. Even using clinically approved liposomal dugs it is possible to find anaphylactic shocks, which can be highly toxic for the treated patient. A team of researchers led by Prof. Bert Müller from the Biomaterials Science Center of the University of Basel and Prof. Andreas Zumbühl from the Department of Chemistry at the University of Fribourg has tested artificial phospholipid vesicles (Pad-PC-Pad vesicles) for their potential as drug delivery nanocontainers. Surprisingly, these liposomes did not spur any reaction neither in blood serum of pigs nor humans. In a next step, the vesicles were tested in living organisms. The researchers injected three Yorkshire pigs with Pad-PC-Pad suspensions and monitored the heart rate, the electrocardiogram and the blood pressures. Even at high doses the pigs showed no or negligible reactions. The biopsies of pig tissues showed no toxic changes in kidneys, lungs, heart, and liver. "The study shows that Pad-PC-Pad liposomes are not inducing direct or indirect anaphylactic reactions, even at high dosages", says Professor Bert Müller of the University of Basel. "These are highly unexpected results could have a high impact of future treatments of atherosclerosis." According to the World Health Organization WHO coronary artery diseases are responsible for 30 percent of deaths worldwide. In the case of constricted coronary arteries the conditions often gets worse during the transport of the patient to the hospital, showing the need for medication that efficiently covers the pre-hospital segment. Pad-PC-Pad vesicles therefore show high potential because, in contrast to existing liposomes, they do not elicit a significant immune response.

News Article | March 14, 2016

Abstract: Liposomes are currently used as drug delivery vehicles but recognized by the immune system. Scientists from the universities of Basel and Fribourg have shown that special artificial liposomes do not elicit any reaction in human and porcine sera as well as pigs. The study was published in the Journal Nanomedicine: Nanotechnology, Biology, and Medicine. Liposomes are soap-bubble-like nanocontainers made of a double phospholipid membrane that shields off an inner aqueous compartment. In a lenticular form, as developed by Professor Andreas Zumbühl's team at the Department of Chemistry at the University of Fribourg, they are promising candidates for drug delivery to constricted coronary arteries. Here, the blood flows through the stenosed artery segments with high velocity and is subjected to enhanced shear forces. Under these conditions, the liposomes open and release their content. Unfortunately, the immune system does recognize these liposomes as foreign bodies. The activation of the immune system may lead to a pseudo-allergy. Earlier studies have shown that negative effects are found in up to 30 percent of the cases. Even using clinically approved liposomal dugs it is possible to find anaphylactic shocks, which can be highly toxic for the treated patient. No Reaction in Pig Studies A team of researchers led by Prof. Bert Müller from the Biomaterials Science Center of the University of Basel and Prof. Andreas Zumbühl from the Department of Chemistry at the University of Fribourg has tested artificial phospholipid vesicles (Pad-PC-Pad vesicles) for their potential as drug delivery nanocontainers. Surprisingly, these liposomes did not spur any reaction neither in blood serum of pigs nor humans. In a next step, the vesicles were tested in living organisms. The researchers injected three Yorkshire pigs with Pad-PC-Pad suspensions and monitored the heart rate, the electrocardiogram and the blood pressures. Even at high doses the pigs showed no or negligible reactions. The biopsies of pig tissues showed no toxic changes in kidneys, lungs, heart, and liver. "The study shows that Pad-PC-Pad liposomes are not inducing direct or indirect anaphylactic reactions, even at high dosages", says Professor Bert Müller of the University of Basel. "These are highly unexpected results could have a high impact of future treatments of atherosclerosis." According to the World Health Organization WHO coronary artery diseases are responsible for 30 % of deaths worldwide. In the case of constricted coronary arteries the conditions often gets worse during the transport of the patient to the hospital, showing the need for medication that efficiently covers the pre-hospital segment. Pad-PC-Pad vesicles therefore show high potential because, in contrast to existing liposomes, they do not elicit a significant immune response. For more information, please click If you have a comment, please us. Issuers of news releases, not 7th Wave, Inc. or Nanotechnology Now, are solely responsible for the accuracy of the content.

News Article | August 26, 2016

Home > Press > Forces of nature: Interview with microscopy innovators Gerd Binnig and Christoph Gerber Abstract: The inventors of one of the most versatile tools in modern science - the atomic force microscope, or AFM - tell their story in an interview published online this week. The AFM was invented in the mid 1980s by Gerd Binnig, Christoph Gerber and Calvin Quate, three physicists who are sharing the 2016 Kavli Prize in Nanoscience. Binnig and Gerber discuss their inspiration for the device, how they solved problems through sport, and why their invention continues to propel science at the nanoscale. "AFM has turned into the most powerful and most versatile toolkit that we have for doing nanoscience. And it keeps evolving," said Gerber in the interview. Gerber is a professor of physics at the Swiss Nanoscience Institute, part of the University of Basel. "In just the past few years, researchers have learned to pick up a molecule on the tip of an AFM, which we can think of as the needle on a record player, and reveal chemical bonds while imaging molecules on surfaces. Nobody thought that ever would be possible." Unlike optical microscopes, AFM doesn't use light to illuminate an object. Instead, it measures the tiny forces between a sharp tip at the end of a cantilever and the surface of an object. As it scans a surface, what emerges is an image so clear that researchers can even distinguish chemical bonds within a molecule. They can also use the tip to create and cleave those bonds, and push atoms around. "[AFM] lets us look at the molecules that make life possible... and see things we could not see before," said Binnig, who received the Nobel Prize in 1986 for the scanning tunneling microscope, AFM's predecessor. "It teaches us how to make changes to surfaces or molecules that we attempted blindly in the past. And it has been used in so many different scientific studies, from looking at polymers and chemical reactions to modifying surfaces at the atomic level." The complete interview is freely available at: The three Nanoscience laureates will be honored at the Kavli Prize Award Ceremony in Oslo, Norway, on September 6, 2016. The prizes were announced June 2 by the Norwegian Academy of Science and Letters: About The Kavli Foundation The Kavli Prizes recognize scientists for their seminal advances in three research areas: astrophysics, nanoscience and neuroscience. Consisting of a scroll, medal and cash award of one million dollars, a prize in each of these areas is awarded every two years beginning in 2008. Kavli Prize recipients are chosen biennially by three prize committees comprised of distinguished international scientists recommended by the Chinese Academy of Sciences, the French Academy of Sciences, the Max Planck Society, the U.S. National Academy of Sciences and the Royal Society. The 2016 Kavli Prizes will be awarded in Oslo, Norway, on September 6. For detailed information on each of the prizes, the 2016 laureates and their work, and all the Kavli Prize Week events, please see the Kavli Prize website: The Kavli Prizes are a partnership between the Norwegian Academy of Science and Letters, The Kavli Foundation (USA) and the Norwegian Ministry of Education and Research. For more information, please click If you have a comment, please us. Issuers of news releases, not 7th Wave, Inc. or Nanotechnology Now, are solely responsible for the accuracy of the content.

Sarris D.,University of Patras | Siegwolf R.,Paul Scherrer Institute | Korner C.,University of Basel
Agricultural and Forest Meteorology | Year: 2013

Interpreting the isotopic tree-ring responses of pines to drought provides insight into the causes of tree mortality. For this reason, we examine such responses for low elevation Pinus halepensis subsp. brutia trees that neighbor recently desiccated pine stands. A strong correlation between 13C discrimination (Δ) signals recorded in tree-rings and concurrent drought indicates a rapid transfer of newly synthesized assimilates to wood formation. However, in dry years the limited moisture allows only early- to mid-spring and mid- to late-autumn as productive periods. Thus, isotopic signals for summer drought may be missing in tree-rings. Yet, over a 30year observation period, drought clearly reduced both, tree-ring width and Δ13C. Intra-annual microtome slices (1/10mm) indicate the highest δ13C signals in autumn (after growth resumed in response to rainfall) as a likely result of autumn wood (late-wood) incorporating carbon fixed and stored during the summer drought related growth cessation. Thus, non structural carbon reserves accumulating under drought are likely to leave a δ13C fingerprint when complete tree-rings (early-plus late-wood) are analyzed. Both inter- and intra-annually, δ18O in tree-rings from these pines declined following precipitation and in contrast to the rise in temperature. Any evaporative enrichment of leaf water in the heavier isotope under drought appears to be masked by the source water utilized for tree growth. Source water from deeper moisture pools is less enriched in 18O than surface water. Therefore, as inter- or intra-annual drought intensifies, pines appear to use this deep water, which accumulates from precipitation over a series of years. This was also confirmed by Δ13C and tree growth data, as both were best correlated with multiple years of past precipitation rather than with seasonal precipitation. Consequently, the most likely cause of drought induced mortality for such plants is chronic depletion of deeper moisture pools and hydraulic failure rather than C starvation. © 2012 Elsevier B.V.

Voss T.S.,Swiss Tropical and Public Health Institute | Voss T.S.,University of Basel | Bozdech Z.,Nanyang Technological University | Bartfai R.,Radboud University Nijmegen
Current Opinion in Microbiology | Year: 2014

Malaria parasites run through a complex life cycle in the vertebrate host and mosquito vector. This not only requires tightly controlled mechanisms to govern stage-specific gene expression but also necessitates effective strategies for survival under changing environmental conditions. In recent years, the combination of different -omics approaches and targeted functional studies highlighted that Plasmodium falciparum blood stage parasites use heterochromatin-based gene silencing as a unifying strategy for clonally variant expression of hundreds of genes. In this article, we describe the epigenetic control mechanisms that mediate alternative expression states of genes involved in antigenic variation, nutrient uptake and sexual conversion and discuss the relevance of this strategy for the survival and transmission of malaria parasites. © 2014.

Bolliger D.,University of Basel | Gorlinger K.,University of Duisburg - Essen | Tanaka K.A.,Emory University
Anesthesiology | Year: 2010

Fluid resuscitation after massive hemorrhage in major surgery and trauma may result in extensive hemodilution and coagulopathy, which is of a multifactorial nature. Although coagulopathy is often perceived as hemorrhagic, extensive hemodilution affects procoagulants as well as anticoagulant, profibrinolytic, and antifibrinolytic elements, leading to a complex coagulation disorder. Reduced thrombin activation is partially compensated by lower inhibitory activities of antithrombin and other protease inhibitors, whereas plasma fibrinogen is rapidly decreased proportional to the extent of hemodilution. Adequate fibrinogen levels are essential in managing dilutional coagulopathy. After extensive hemodilution, fibrin clots are more prone to fibrinolysis because major antifibrinolytic proteins are decreased.Fresh frozen plasma, platelet concentrate, and cryoprecipitate are considered the mainstay hemostatic therapies. Purified factor concentrates of plasma origin and from recombinant synthesis are increasingly used for a rapid restoration of targeted factors. Future clinical studies are necessary to establish the specific indication, dosing, and safety of novel hemostatic interventions. © 2010, the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins.

Furst T.,Swiss Tropical and Public Health Institute | Furst T.,University of Basel | Keiser J.,Swiss Tropical and Public Health Institute | Keiser J.,University of Basel | And 2 more authors.
The Lancet Infectious Diseases | Year: 2012

Background: Food-borne trematodiases are a group of neglected tropical diseases caused by liver, lung, and intestinal parasitic fluke infections. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD 2010 study) and a WHO initiative, we assessed the global burden of human food-borne trematodiasis, as expressed in disability-adjusted life years (DALYs) for the year 2005. Methods: We systematically searched electronic databases for reports about human food-borne trematodiasis without language restriction, between Jan 1, 1980, and Dec 31, 2008. We used a broad search strategy with a combination of search terms and parasite and disease names. The initial search results were then screened on the basis of title, abstract, and, finally, full text. Relevant quantitative and qualitative data on human prevalence, morbidity, and mortality of food-borne trematodiasis were extracted. On the basis of available information on pathological and clinical appearance, we developed simplified disease models and did meta-analyses on the proportions and odds ratios of specified sequelae and estimated the global burden of human food-borne trematodiasis. Findings: We screened 33 921 articles and identified 181 eligible studies containing quantitative information for inclusion in the meta-analyses. About 56·2 million people were infected with food-borne trematodes in 2005: 7·9 million had severe sequelae and 7158 died, most from cholangiocarcinoma and cerebral infection. Taken together, we estimate that the global burden of food-borne trematodiasis was 665 352 DALYs (lower estimate 479 496 DALYs; upper estimate 859 051 DALYs). Furthermore, knowledge gaps in crucial epidemiological disease parameters and methodological features for estimating the global burden of parasitic diseases that are characterised by highly focal spatial occurrence and scarce and patchy information were highlighted. Interpretation: Despite making conservative estimates, we found that food-borne trematodiases are an important cluster of neglected diseases. Funding: Swiss National Science Foundation; Institute for Health Metrics and Evaluation. © 2012 Elsevier Ltd.

Betz C.,University of Basel | Stracka D.,University of Basel | Prescianotto-Baschong C.,University of Basel | Frieden M.,University of Geneva | And 2 more authors.
Proceedings of the National Academy of Sciences of the United States of America | Year: 2013

The target of rapamycin (TOR) is a highly conserved protein kinase and a central controller of growth. Mammalian TOR complex 2 (mTORC2) regulates AGC kinase family members and is implicated in various disorders, including cancer and diabetes. Here we report that mTORC2 is localized to the endoplasmic reticulum (ER) subcompartment termed mitochondria-associated ER membrane (MAM). mTORC2 localization to MAM was growth factor-stimulated, and mTORC2 at MAM interacted with the IP3 receptor (IP3R)-Grp75-voltage-dependent anion-selective channel 1 ER-mitochondrial tethering complex. mTORC2 deficiency disrupted MAM, causing mitochondrial defects including increases in mitochondrial membrane potential, ATP production, and calcium uptake. mTORC2 controlled MAM integrity and mitochondrial function via Akt mediated phosphorylation of the MAM associated proteins IP3R, Hexokinase 2, and phosphofurin acidic cluster sorting protein 2. Thus, mTORC2 is at the core of a MAM signaling hub that controls growth and metabolism. © PNAS 2013.

Loewith R.,University of Geneva | Hall M.N.,University of Basel
Genetics | Year: 2011

TOR (Target Of Rapamycin) is a highly conserved protein kinase that is important in both fundamental and clinical biology. In fundamental biology, TOR is a nutrient-sensitive, central controller of cell growth and aging. In clinical biology, TOR is implicated in many diseases and is the target of the drug rapamycin used in three different therapeutic areas. The yeast Saccharomyces cerevisiae has played a prominent role in both the discovery of TOR and the elucidation of its function. Here we review the TOR signaling network in S. cerevisiae. © 2011 by the Genetics Society of America.

Coscolla M.,Swiss Tropical and Public Health Institute | Coscolla M.,University of Basel | Gagneux S.,Swiss Tropical and Public Health Institute | Gagneux S.,University of Basel
Seminars in Immunology | Year: 2014

The causative agent of human tuberculosis, Mycobacterium tuberculosis complex (MTBC), comprises seven phylogenetically distinct lineages associated with different geographical regions. Here we review the latest findings on the nature and amount of genomic diversity within and between MTBC lineages. We then review recent evidence for the effect of this genomic diversity on mycobacterial phenotypes measured experimentally and in clinical settings. We conclude that overall, the most geographically widespread Lineage 2 (includes Beijing) and Lineage 4 (also known as Euro-American) are more virulent than other lineages that are more geographically restricted. This increased virulence is associated with delayed or reduced pro-inflammatory host immune responses, greater severity of disease, and enhanced transmission. Future work should focus on the interaction between MTBC and human genetic diversity, as well as on the environmental factors that modulate these interactions. © 2014 The Authors.

De Cabo R.,U.S. National Institute on Aging | Carmona-Gutierrez D.,University of Graz | Bernier M.,U.S. National Institute on Aging | Hall M.N.,University of Basel | Madeo F.,University of Graz
Cell | Year: 2014

The phenomenon of aging is an intrinsic feature of life. Accordingly, the possibility to manipulate it has fascinated humans likely since time immemorial. Recent evidence is shaping a picture where low caloric regimes and exercise may improve healthy senescence, and several pharmacological strategies have been suggested to counteract aging. Surprisingly, the most effective interventions proposed to date converge on only a few cellular processes, in particular nutrient signaling, mitochondrial efficiency, proteostasis, and autophagy. Here, we critically examine drugs and behaviors to which life- or healthspan-extending properties have been ascribed and discuss the underlying molecular mechanisms. © 2014 Elsevier Inc.

Archetti M.,University of East Anglia | Ferraro D.A.,University of Basel | Christofori G.,University of Basel
Proceedings of the National Academy of Sciences of the United States of America | Year: 2015

The extensive intratumor heterogeneity revealed by sequencing cancer genomes is an essential determinant of tumor progression, diagnosis, and treatment. What maintains heterogeneity remains an open question because competition within a tumor leads to a strong selection for the fittest subclone. Cancer cells also cooperate by sharing molecules with paracrine effects, such as growth factors, and heterogeneity can be maintained if subclones depend on each other for survival. Without strict interdependence between subclones, however, nonproducer cells can free-ride on the growth factors produced by neighboring producer cells, a collective action problem known in game theory as the "tragedy of the commons," which has been observed in microbial cell populations. Here, we report that similar dynamics occur in cancer cell populations. Neuroendocrine pancreatic cancer (insulinoma) cells that do not produce insulin-like growth factor II (IGF-II) grow slowly in pure cultures but have a proliferation advantage in mixed cultures, where they can use the IGF-II provided by producer cells. We show that, as predicted by evolutionary game theory, producer cells do not go extinct because IGF-II acts as a nonlinear public good, creating negative frequency-dependent selection that leads to a stable coexistence of the two cell types. Intratumor cell heterogeneity can therefore be maintained even without strict interdependence between cell subclones. Reducing the amount of growth factors available within a tumor may lead to a reduction in growth followed by a new equilibrium, which may explain relapse in therapies that target growth factors. game theory tumor evolution We thank Dieter Ebert, István Scheuring, Dylan Edwards, and Stephen Robinson for comments on the manuscript; Stephen Robinson, Aleksander Gontarczyk, and Linh Le for help with cell culture; and Ernesta Fagiani and Darren Sexton for help with flow cytometry.

Saxer T.,University of Geneva | Zumbuehl A.,University of Fribourg | Muller B.,University of Basel
Cardiovascular Research | Year: 2013

Stenosed segments of arteries significantly alter the blood flow known from healthy vessels. In particular, the wall shear stress at critically stenosed arteries is at least an order of magnitude higher than in healthy situations. This alteration represents a change in physical force and might be used as a trigger signal for drug delivery. Mechano-sensitive drug delivery systems that preferentially release their payload under increased shear stress are discussed. Therefore, besides biological or chemical markers, physical triggers are a further principle approach for targeted drug delivery. We hypothesize that such a physical trigger is much more powerful to release drugs for vasodilation, plaque stabilization, or clot lysis at stenosed arteries than any known biological or chemical ones. © The Author 2013.

Alonso P.L.,University of Barcelona | Alonso P.L.,Manhica Health Research Center | Tanner M.,Swiss Tropical and Public Health Institute | Tanner M.,University of Basel
Nature Medicine | Year: 2013

The past decade witnessed unprecedented efforts to control malaria, including renewed political and financial commitment and increased availability of both old and new strategies and tools. However, malaria still represents a major health burden, particularly in Africa. Important challenges such as the fragility of many health systems, the rise of insecticide and drug resistance, and particularly the expected decline both in funding and in the coverage of key interventions if they are not replaced as needed, urgently need to be addressed. Further research and development is also becoming increasingly crucial. Among other needs, common methodologies for estimating and tracking the malaria burden, new strategies to measure transmission, better understanding of immunity, and increased knowledge of the mechanisms and effects of resistance to drugs and insecticides stand out. The ongoing efforts in research and development for new antimalarial drugs, more sensitive point-of-care rapid diagnostic tests and new insecticides need further innovation and substantial strengthening. Clearly, efforts should focus not only on Plasmodium falciparum but also and increasingly on Plasmodium vivax, the neglected human malaria parasite. Addressing these challenges in a comprehensive and timely way will allow us to sustain the gains made so far and make further progress in control and progressive elimination. © 2013 Nature America, Inc. All rights reserved.

Irla M.,University of Geneva | Hollander G.,University of Basel | Reith W.,University of Geneva
Trends in Immunology | Year: 2010

Medullary thymic epithelial cells (mTECs) are crucial for the selection of a T-cell-receptor (TCR) repertoire purged of self-reactive specificities, because these cells activate a promiscuous gene-expression program that leads to the synthesis of a wide array of peripheral tissue-restricted self-antigens. This review summarizes recent progress in our understanding of the cellular interactions, ligands, receptors and signal-transduction pathways that control mature-mTEC development. The particular focus is on new findings supporting the model that mature-mTEC development in the postnatal thymus depends on nuclear factor-κB (NF-κB) signaling induced by CD40-CD40 ligand, and receptor-activator-of-NF-κB (RANK)-RANK ligand interactions, and that these signals are delivered in the context of antigen-specific interactions between CD4+ thymocytes carrying autoreactive TCRs and mTECs displaying cognate autoantigen-MHC-class-II complexes. © 2009 Elsevier Ltd. All rights reserved.

Comas I.,UK National Institute for Medical Research | Gagneux S.,Swiss Tropical and Public Health Institute | Gagneux S.,University of Basel
Trends in Microbiology | Year: 2011

Despite being a curable disease, tuberculosis (TB) killed more people in 2009 than during any previous year in history. Progress in TB research has been slow, and remains burdened by important gaps in our knowledge of the basic biology of Mycobacterium tuberculosis, the causative agent of TB, and its interaction with the human host. Fortunately, major systems biology initiatives have recently been launched that will help fill some of these gaps. However, to fully comprehend TB and control this disease globally, current systems biological approaches will not suffice. The influence of host and pathogen diversity, changes in human demography, and socioeconomic and environmental factors will also need to be considered. Such a multidisciplinary approach might be best described as 'systems epidemiology' in an effort to overcome the traditional boundaries between basic biology and classical epidemiology. © 2011 Elsevier Ltd.

Stano P.,Slovak Academy of Sciences | Stano P.,University of Basel | Jacquod P.,University of Arizona | Jacquod P.,University of Geneva
Nature Photonics | Year: 2013

Understanding random lasing is a formidable theoretical challenge. Unlike conventional lasers, random lasers have no resonator to trap light, they are highly multimode with potentially strong modal interactions, and they are based on disordered gain media, where photons undergo random multiple scattering. Interference effects notoriously modify the propagation of waves in such random media, but their fate in the presence of nonlinearity and interactions is poorly understood. Here, we present a semiclassical theory for multimode random lasing in the strongly scattering regime. We show that Anderson localization, a wave interference effect, is not affected by the presence of nonlinearities. To the contrary, its presence suppresses interactions between simultaneously lasing modes. Consequently, each lasing mode in a strongly scattering random laser is given by a single long-lived, Anderson localized mode of the passive cavity, the frequency and wave profile of which do not vary with pumping, even in the multimode regime when modes spatially overlap. © 2013 Macmillan Publishers Limited.

Agency: Cordis | Branch: FP7 | Program: MC-IOF | Phase: FP7-PEOPLE-2013-IOF | Award Amount: 375.81K | Year: 2014

Cancer is a process of clonal selection, and analytical methods from evolutionary biology should be able to explain why cancer tissues are heterogeneous and develop resistance to current therapies. Evolutionary game theory helps understand non-intuitive properties of the frequency-dependent dynamics arising in the cooperative interactions between cancer cells. In particular, the theory of N-person non-linear public goods games is used to analyse the evolutionary dynamics of the production of diffusible molecules like growth factors, which are essential in the development of cancer. Models that take into account general features of non-linear public goods in structured populations, as well as specific features of certain types of growth factors, are used to understand the ultimate causes of tissue heterogeneity and of the evolution of resistance to therapies. The second part of the project uses experiments with cancer cell populations in vitro to test the predictions of the theory. Two types of beta cells from insulinomas of mouse, one of which knocked out for insulin-like growth factor-II (IGF-II), a factor that promotes cancer cell proliferation and survival, are used for experimental evolution in vitro. It is anticipated that IGF-II-deficient tumour cells, while unable to grow in the absence of IGF-II, will proliferate better than producer cells when IGF-II is provided exogenously or by co-cultured producer cells, making IGF-II a public good, and providing an example of cooperation among cancer cells. The results will help understand stable intra-tumoural cell heterogeneity, why therapies that target growth factors lead to a temporary reduction in tumour growth followed by relapse, and may help devise evolutionarily stable therapies.

Agency: Cordis | Branch: FP7 | Program: CP | Phase: ICT-2011.9.1 | Award Amount: 2.63M | Year: 2013

Quantum phenomena are an important basis for future information processing and information acquisition technologies. They will become particularly relevant for quantum-enhanced metrology and advanced sensors, which exploit the quantum superposition principle at a mesoscopic scale.\n\nNANOQUESTFIT will prepare nanoparticles in highly non-classical quantum states and utilize them to test the linearity of quantum physics over mesoscopic distances and time scales in a mass range that has remained hitherto unexplored. This goal will be realized in an interdisciplinary effort of European experts in quantum optics, nanotechnology, chemistry, and cluster physics.\n\nNANOQUESTFIT will realize novel quantum optical elements, such as optical depletion and phase gratings, atomically thin transmission gratings, as well as doped substrates in ultra-flat silicon. This will enable quantum coherence and interference studies with objects up to and beyond 10^5 atomic mass units for the first time.\n\nFor that purpose new beam methods will be explored for tailor-made nanoparticles between 10^4 and 10^7 atomic mass units. This includes the efficient volatilization and detection of chemically functionalized nanoparticles, of pure and doped nanodroplets, as well as of cold slow cluster ions.\n\nDecoherence is the enemy of all future quantum-based technologies. The consortium will therefore investigate environmental decoherence with objects in a complexity class that is expected to become relevant in future quantum devices.\n\nAdvanced experiments in NANOQUESTFIT will allow defining new constraints on unconventional extensions of quantum theory, which will be explored and elaborated on with regard to their conceptional consistency. Since the linearity of the Schrdinger equation is the very basis for the majority of current quantum information concepts this has direct implications for QIPC.\n\nNANOQUESTFIT works at the cutting edge of modern science to lay the scientific ground for a better understanding of practical and fundamental limits of future quantum technologies. It will also generate spin-offs for new quantum-enhanced sensing devices: in particular the beam splitter technologies developed in NANOQUESTFIT will be applicable to a wide range of matter waves composed of atoms, molecules and genuine nanoparticles.

Agency: Cordis | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-2012-ITN | Award Amount: 3.31M | Year: 2013

Our ITN has both scientific and therapeutic targets. Research in Work Package 1 (WP1) aims to advance understanding of normal blood cell development and why primitive cells fail to differentiate in acute myeloid leukaemia (AML). Research in WP2 will use the information gained from WP1 to develop ways of alleviating the differentiation block in AML and so deliver new agents for use in differentiation therapy. This type of therapy aims, using only mildly toxic treatments, to induce terminal maturation of leukaemia cells and accelerate their death. WP2 responds to the urgent need to devise milder treatments, especially for older and frailer AML patients. Participants have already identified a number of promising new therapeutic agents. Working across these two complementary areas will train our Early Stage Researchers (ESR) to understand the translation of new fundamental science into the development of new therapies. The ITN brings together scientists who have made important advances in the fields of haematopoiesis and differentiation therapy, so will provide an excellent scientific training in these areas. Secondments/visits by ESRs to participants who run centres of expertise in leading edge technologies will provide training in these; and the time spent with private sector participants, and the courses they provide, will ensure that ESRs acquire the transferable skills they will need if they are to work well in, and build bridges between, commercial and publicly funded research organisations. ESRs will also receive management training. This research and training, which will develop our ESRs as versatile scientists, will involve the combined efforts of prestigious research institutes and universities, Polands leading governmental pharmaceutical R & D institute, two successful biopharmaceutical companies and a leading management consultancy.

Agency: Cordis | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-2013-ITN | Award Amount: 3.02M | Year: 2013

Aneuploidy, an abnormal number of chromosomes, is a hallmark of cancer cells, affecting the majority of all human tumours. Aneuploidy arises when errors occur during mitosis, as the duplicated chromosomes are distributed between the two new daughter cells. Paradoxically, aneuploidy appears to have detrimental consequences for the physiology of untransformed cells in vitro, inhibiting rather than stimulating proliferation. This suggests that cancer cells have acquired mutations that help them cope with aneuploidy. Although it is clear that aneuploidy can contribute to cancer, the molecular consequences of aneuploidy remain elusive, as does how aneuploidy contributes to malignant transformation. The scientific aim of this network is to determine and compare the molecular consequences of different levels of aneuploidy, both in vivo and in vitro. Our network will train 9 Early Stage Career and 2 Experienced researchers in the aneuploidy field. To this aim, we are combining the expertise of labs that study the causes of aneuploidy with labs that induce aneuploidy in model organisms and study its consequences and also with labs that focus on the development of therapeutics that selectively kill aneuploid cell progeny. Our network is comprised of 11 full participants in 4 member states and 1 associated country and one associated partner, and includes 3 commercial enterprises. Within this network, we will provide technical training through research projects, but also through workshops and dedicated courses organized by the participants of this network. A significant part of the training will be provided by the industrial partners. Participating investigators and trainees will meet at a yearly conference to exchange and discuss results. Trainees will thus become experts in the field of aneuploidy while rapidly building up a scientific network for themselves, putting them in an excellent position to become future leaders in this field.

University of Basel and PIQUR Therapeutics | Date: 2014-10-03

The invention relates to novel phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) inhibitor compounds of formula (I) and (II), which are conformationally restricted, and for which the meaning of the substituents are listed in the description. Preferred compounds are those wherein X isoxygen, R_(1 )is morpholino and R_(2 )is substituted phenyl or heteroaryl. These compounds are useful, either alone or in combination with further therapeutic agents, for treating disorders mediated by lipid kinases.

Agency: Cordis | Branch: FP7 | Program: ERC-SG | Phase: ERC-SG-LS6 | Award Amount: 1.50M | Year: 2013

This project aims for a quantum leap in the understudied area of memory B cell immunity to chronic viral infection. It provides i) a landscape analysis of primary and memory B cell responses to chronic viral challenge, ii) investigates receptor hypermutation of memory B cells for broadened protection against viral escape variants, and iii) studies the role of memory CD4\ T cells in augmenting memory B cell protection in chronic viral infection. Memory B cells represent a main pillar of immunological memory and account for long-term protection by the hepatitis B virus vaccine, the only one to afford protection against a persistent viral infection in humans. Yet our understanding of memory B cell immunity to chronic viral infection remains rudimentary, owing to a lack of advanced methodology and model systems for its investigation. My laboratory has developed a comprehensive set of tools to overcome these hurdles in the prototypic chronic infection model of lymphocytic choriomeningitis virus (LCMV) in mice. We have at hands the first LCMV-neutralizing monoclonal B cell receptor-expressing mouse (unpublished), and will collaborate with a world-leading lab in B cell biology to exploit their novel mouse model for in vivo tracing of polyclonal antigen-specific memory B cells. Combined with genetically engineered LCMV mutants, multi-parameter flow cytometry, state-of-the-art immunological methods, histopathology and deep sequencing of B cell receptor repertoires, these models will allow for unprecedented cell transfer and viral infection studies in vivo. Our leading expertise in LCMV molecular biology and immunology, combined with our partners expertise in B cell biology warrants for a high likelihood of success in this ambitious journey to virgin territory. We expect this project to provide a conceptual basis and incentive to successfully exploit memory B cell immunity in the battle against global hepatitis C virus and human immunodeficiency virus pandemics.

Sepstone Diagnostics Sarl and University of Basel | Date: 2011-05-31

The present invention relates to a reliable method of prediction of lower respiratory tract infection or inflammation in humans, wherein the level of pancreatic stone protein/regenerating protein (PSP/reg) is determined in serum, and a high level is indicative of the development and the severity of the disease, allowing the classification of patients according to risk.

News Article | March 15, 2016

A spindly toad-eating spider that creates vibrational waves on the water's surface in order to navigate and capture prey has been discovered in Brisbane, Australia, scientists announced at the World Science Festival last week. They named the fish-eating spider Dolomedes briangreenei after theoretical physicist Brian Greene, who is also co-founder of the World Science Festival where the spider was described. "It's wonderful that this beautiful native spider, which relies on waves for its very survival, has found a namesake in a man who is one of the world's leading experts in exploring and explaining the effects of waves in our universe," Queensland Premier Annastacia Palaszczuk said in an emailed statement, referring to gravitational waves, or ripples in the very fabric of space-time. [See Photos of Fish-Eating Spiders from Around the World] Greene said he is "honored to be so closely associated with a spider that has its own deep affinity for waves." (Physicists announced last month they had detected for the first time such gravitational waves.) Dolomedes briangreenei males sport bold white stripes along the sides of the head, while females have a narrower, fawn-colored stripe on either side of the head, according to the statement. The dark, leggy spider snacks on fish, frogs and tadpoles; the spider also makes a meal of the invasive cane toad, Rhinella marina, whose females can weigh up to 3.3 pounds (1.5 kilograms), according to the U.S. Geological Survey. When asked to comment on the newfound Dolomedes spider, Martin Nyffeler, a senior lecturer of zoology at the University of Basel in Switzerland, who was not involved in this new research, told Live Science: "The spiders in the genus Dolomedes are spiders of fairly large size, which often reach a live weight of up to 2 grams. These spiders are known to kill fish, frogs, toads, lizards and even small snakes." Dolomedes spiders can take down such large prey — up to 4.5 times their own weight, according to Nyffeler — by first using their long legs to lunge at a victim, biting the prey with its chelicerae, or the spider's mouthparts, Nyffeler said. "Many other spiders’ chelicerae are not that strong," he added in an email. The Dolomedes spider then injects powerful neurotoxins into its prey. Spiders in the Dolomedes genus are members of the Pisauridae family, which is related to another spider family with a big appetite: Lycosidae. Two Australian wolf spiders in the Lycosidae family (Lycosa lapidosa and Lycosa obscuroides) are known to take down cane toads, he said. "Both families belong to the superfamily Lycosoidea, which does contain numerous powerful species capable of devouring frogs and toads. I assume that the cane toads killed by such spiders might be rather smaller-sized juveniles, but I don't know this," Nyffeler wrote. Not only do they go big for dinner, the water spiders are also strong swimmers and can even propel themselves across the surface of the water with their two middle leg pairs. "When disturbed or hauling in captured fish, they will plunge through the surface of the water and swim quickly to hide on the bottom," Robert Raven, Queensland Museum arachnologist, said in the statement. The World Science Festival Brisbane, where big thinkers and artists from around the world celebrate "the beauty and complexity of science," according to the WSF, ran from March 9–13; the festival in New York City will kick off on June 1. Copyright 2016 LiveScience, a Purch company. All rights reserved. This material may not be published, broadcast, rewritten or redistributed.

News Article | October 25, 2016

A new type of atomic force microscope (AFM) uses nanowires as tiny sensors. Unlike standard AFM, the device with a nanowire sensor enables measurements of both the size and direction of forces. Physicists at the University of Basel and at the EPF Lausanne have described these results in the recent issue of Nature Nanotechnology.

Sawarkar R.,ETH Zurich | Sievers C.,ETH Zurich | Paro R.,ETH Zurich | Paro R.,University of Basel
Cell | Year: 2012

The molecular chaperone Heat shock protein 90 (Hsp90) promotes the maturation of several important proteins and plays a key role in development, cancer progression, and evolutionary diversification. By mapping chromatin-binding sites of Hsp90 at high resolution across the Drosophila genome, we uncover an unexpected mechanism by which Hsp90 orchestrates cellular physiology. It localizes near promoters of many coding and noncoding genes including microRNAs. Using computational and biochemical analyses, we find that Hsp90 maintains and optimizes RNA polymerase II pausing via stabilization of the negative elongation factor complex (NELF). Inhibition of Hsp90 leads to upregulation of target genes, and Hsp90 is required for maximal activation of paused genes in Drosophila and mammalian cells in response to environmental stimuli. Our findings add a molecular dimension to the chaperone's functionality with wide ramifications into its roles in health, disease, and evolution. © 2012 Elsevier Inc.

Fathi A.-R.,Cantonal Hospital | Roelcke U.,Cantonal Hospital | Roelcke U.,University of Basel
Current Neurology and Neuroscience Reports | Year: 2013

Meningiomas represent the most common primary brain tumor and comprise 3 World Health Organization (WHO) grades, the most frequent being WHO grade I (90 %). Surgery is mandatory to establish the diagnosis and to remove the tumor; however, complete resection can be achieved in only <50 % of patients. Depending on the extent of resection, tumor location and the WHO grade radiation therapy can be applied. The issue of systemic treatment such as chemotherapy or targeted therapy (eg, somatostatin receptors, antiangiogenic agents) is yet not solved, particularly as current data are derived from small uncontrolled series in patients with long-standing disease and after several pretreat-ments. a more thorough understanding of molecular genetics, signaling pathways and prognostic factors in meningiomas should lead to the design of studies which stratify according to these factors. These studies have to be conducted in newly diagnosed patients after incomplete resection and in tumors of WHO grade II and III. © Springer Science+Business Media New York 2013.

Leuzinger S.,University of Basel | Leuzinger S.,ETH Zurich | Korner C.,University of Basel
Global Change Biology | Year: 2010

Reduced stomatal conductance under elevated CO2 results in increased soil moisture, provided all other factors remain constant. Whether this results in increased runoff critically depends on the interaction of rainfall patterns, soil water storage capacity and plant responses. To test the sensitivity of runoff to these parameters under elevated CO2,we combine transpiration and soil moisture data from the Swiss Canopy Crane FACE experiment (SCC, 14 30-35 m tall deciduous broad-leaved trees under elevated CO2) with 104 years of daily precipitation data from an adjacent weather station to drive a three-layer bucket model (mean yearly precipitation 794 mm). The model adequately predicts the water budget of a temperate deciduous forest and runoff from a nearby gauging station. A simulation run over all 104 years based on measured sap flow responses resulted in only 5.5 mm (2.9%) increased ecosystem runoff under elevated CO2. Out of the 37 986 days (1 January 1901-31 December 2004), only 576 days produce higher runoff in the elevated CO2 scenario. Only 1 out of 17 years produces a CO2-signal >20 mm a-1, which mostly depends on a few single days when runoff under elevated CO2 exceeds runoff under ambient conditions. The maximum signal for a double preindustrial CO2-concentration under the past century daily rainfall regime is an additional runoff of 46 mm. More than half of all years produce a signal of <5mma-1, because trees consume the 'extra' moisture during prolonged dry weather. Increased runoff under elevated CO2 is nine times more sensitive to variations in rain pattern than to the applied reduction in transpiration under elevated CO2. Thus the key driver of increased runoff under future CO2-concentration is the day by day rainfall pattern. We argue that increased runoff due to a first-order plant physiological CO2-effect will be very small (<3%) in a landscape dominated by temperate deciduous forests, and will hardly increase flooding risk in forest catchments. Monthly rainfall sums are unsuitable to realistically model such CO2 effects. These findings may apply to other ecosystems with comparable soil water storage capacity. © 2009 Blackwell Publishing Ltd.

Peleg O.,ETH Zurich | Lim R.Y.H.,University of Basel
Biological Chemistry | Year: 2010

Several biological mechanisms involve proteins or proteinaceous components that are intrinsically disordered. A case in point pertains to the nuclear pore complex (NPC), which regulates molecular transport between the nucleus and the cytoplasm. NPC functionality is dependent on unfolded domains rich in Phe-Gly (FG) repeats (i.e., FG-domains) that collectively act to promote or hinder cargo translocation. To a large extent, our understanding of FG-domain behavior is limited to in vitro investigations given the difficulty to resolve them directly in the NPC. Nevertheless, recent findings indicate a collective convergence towards rationalizing FG-domain function. This review aims to glean further insight into this fascinating problem by taking an objective look at the boundary conditions and contextual details underpinning FG-domain behavior in the NPC. Here, we treat the FG-domains as being commensurate with polymeric chains to address ambiguities such as for instance, how FG-domains tethered to the central channel of the NPC would behave differently as compared with their free-floating counterparts in solution. By bringing such fundamental questions to the fore, this review seeks to illuminate the importance of how such parameters can hold influence over the structure-function relation of intrinsically disordered proteins in the NPC and beyond. © 2010 by Walter de Gruyter Berlin New York.

Hiller S.,University of Basel | Wider G.,ETH Zurich
Topics in Current Chemistry | Year: 2012

This chapter presents the NMR technique APSY (automated projection spectroscopy) and its applications for sequence-specific resonance assignments of proteins. The result of an APSY experiment is a list of chemical shift correlations for an N-dimensional NMR spectrum (N > 3). This list is obtained in a fully automated way by the dedicated algorithm GAPRO (geometric analysis of projections) from a geometric analysis of experimentally recorded, low-dimensional projections. Because the positions of corresponding peaks in multiple projections are correlated, thermal noise and other uncorrelated artifacts are efficiently suppressed. We describe the theoretical background of the APSY method and discuss technical aspects that guide its optimal use. Further, applications of APSY-NMR spectroscopy for fully automated sequence-specific backbone and side chain assignments of proteins are described. We discuss the choice of suitable experiments for this purpose and show several examples. APSY is of particular interest for the assignment of soluble unfolded proteins, which is a time-consuming task by conventional means. With this class of proteins, APSY-NMR experiments with up to seven dimensions have been recorded. Sequence-specific assignments of protein side chains in turn are obtained from a 5D TOCSY-APSY-NMR experiment. © 2011 Springer-Verlag Berlin Heidelberg.

Comi G.,University of Milan | Jeffery D.,Advance Neurology and Pain | Kappos L.,University of Basel | Montalban X.,Autonomous University of Barcelona | And 4 more authors.
New England Journal of Medicine | Year: 2012

BACKGROUND: Two proof-of-concept clinical trials have provided evidence that laquinimod reduces disease activity in patients with relapsing-remitting multiple sclerosis. METHODS: We conducted a randomized, double-blind, phase 3 study at 139 sites in 24 countries. A total of 1106 patients with relapsing-remitting multiple sclerosis were randomly assigned in a 1:1 ratio to receive oral laquinimod at a dose of 0.6 mg once daily or placebo for 24 months. The primary end point was the annualized relapse rate during the 24-month period. Secondary end points included confirmed disability progression (defined as an increase in the score on the Expanded Disability Status Scale that was sustained for at least 3 months) and the cumulative number of gadolinium-enhancing lesions and new or enlarging lesions on T 2-weighted magnetic resonance imaging. RESULTS: Treatment with laquinimod as compared with placebo was associated with a modest reduction in the mean (±SE) annualized relapse rate (0.30±0.02 vs. 0.39±0.03, P = 0.002) and with a reduction in the risk of confirmed disability progression (11.1% vs. 15.7%; hazard ratio, 0.64; 95% confidence interval, 0.45 to 0.91; P = 0.01). The mean cumulative numbers of gadolinium-enhancing lesions and new or enlarging lesions on T 2-weighted images were lower for patients receiving laquinimod than for those receiving placebo (1.33±0.14 vs. 2.12±0.22 and 5.03±0.08 vs. 7.14±0.07, respectively; P<0.001 for both comparisons). Transient elevations in alanine aminotransferase levels to greater than three times the upper limit of the normal range were observed in 24 patients receiving laquinimod (5%) and 8 receiving placebo (2%). CONCLUSIONS: In this phase 3 study, oral laquinimod administered once daily slowed the progression of disability and reduced the rate of relapse in patients with relapsing-remitting multiple sclerosis. (Funded by Teva Pharmaceutical Industries; number, NCT00509145.) Copyright © 2012 Massachusetts Medical Society.

Ben-Ami F.,University of Basel | Ebert D.,University of Basel | Regoes R.R.,ETH Zurich
American Naturalist | Year: 2010

Stress conditions have been found to change the susceptibility of hosts or their offspring to infection. The usual method of testing at just one parasite dose level does not allow conclusions on the distribution of susceptibility. To better understand the epidemiology and evolution of host-parasite systems, however, knowledge about the distribution of host susceptibility, the parameters that characterize it, and how it changes in response to environmental conditions is required. We investigated transgenerational effects of different stress factors by exposing Daphnia magna to standard conditions, to low food levels, or to a high dose of the bacterial pathogen Pasteuria ramosa and then measuring the susceptibility of the offspring to different spore doses of the parasite. For the analysis we used a mathematical model that predicts the fraction of infected hosts at different parasite doses, allowing us to estimate the mean and variance of host susceptibility. We find that low food levels reduce both the mean and the variance of offspring susceptibility. Parasite exposure, on the other hand, widens the offspring's susceptibility distribution without affecting its mean. Our analysis uncovered previously unknown transgenerational effects on the distribution of susceptibilities. The finding of an alteration in the variance of susceptibility to infection has implications for host and parasite dynamics and can contribute to our understanding of the stability of hostparasite interactions. © 2009 by The University of Chicago.

Auslander S.,ETH Zurich | Fussenegger M.,ETH Zurich | Fussenegger M.,University of Basel
Trends in Biotechnology | Year: 2013

Nature has evolved a treasury of biological molecules that are logically connected to networks, enabling cells to maintain their functional integrity. Similar to electronic circuits, cells operate as information-processing systems that dynamically integrate and respond to distinct input signals. Synthetic biology aims to standardize and expand the natural toolbox of biological building blocks to engineer novel synthetic networks in living systems. Mammalian cells harboring integrated designer circuits could work as living biocomputers that execute predictable metabolic and therapeutic functions. This review presents design principles of mammalian gene circuits, highlights recent developments, and discusses future challenges and prospects. © 2012 Elsevier Ltd.

Iber D.,ETH Zurich | Zeller R.,University of Basel
Current Opinion in Genetics and Development | Year: 2012

Limb bud development has been studied for decades and contributed a wealth of knowledge to our understanding of the molecular and cellular mechanisms that govern organogenesis in vertebrate embryos. However, the general regulatory paradigms that underlie the functional and structural organization of complex systems such as developing limb buds have remained largely elusive. A significant number of mathematical theories have been proposed to explain these developmental processes, but have rarely been validated by experimental analysis. In the age of systems biology, experimental and mathematical approaches have become interlinked and enable the experimental validation of computational models by molecular and genetic analysis. This in turn allows refinement of the mathematical simulations such that simulating limb bud development becomes increasingly more realistic. The resulting models not only detect inconsistencies in the interpretation of experimental data, but their predictive power facilitates identification of key regulatory interactions and definition of so-called core and accessory mechanisms. The ongoing integrative analysis of vertebrate limb organogenesis indicates that these network simulations may be suitable for in silico genetics, that is the computational modeling of complex loss-of-functions and gain-of-functions states. Such in silico genetic approaches will permit the simulation of complex mutant phenotypes tedious or impossible to generate using mouse molecular genetics. © 2012 Elsevier Ltd.

Rossger K.,ETH Zurich | Hamri G.C.-E.,Institut Universitaire de France | Fussenegger M.,ETH Zurich | Fussenegger M.,University of Basel
Proceedings of the National Academy of Sciences of the United States of America | Year: 2013

Synthetic biology has significantly advanced the design of synthetic trigger-controlled devices that can reprogram mammalian cells to interface with complex metabolic activities. In the brain, the neurotransmitter dopamine coordinates communication with target neurons via a set of dopamine receptors that control behavior associated with reward-driven learning. This dopamine transmission has recently been suggested to increase central sympathetic outflow, resulting in plasma dopamine levels that correlate with corresponding brain activities. By functionally rewiring the human dopamine receptor D1 (DRD1) via the second messenger cyclic adenosine monophosphate (cAMP) to synthetic promoters containing cAMP response element-binding protein 1 (CREB1)-specific cAMP-responsive operator modules, we have designed a synthetic dopamine-sensitive transcription controller that reversibly fine-tunes specific target gene expression at physiologically relevant brain-derived plasma dopamine levels. Following implantation of circuit-transgenic human cell lines insulated by semipermeable immunoprotective microcontainers into mice, the designer device interfaced with dopamine-specific brain activities and produced a systemic expression response when the animal's reward system was stimulated by food, sexual arousal, or addictive drugs. Reward-triggered brain activities were able to remotely program peripheral therapeutic implants to produce sufficient amounts of the atrial natriuretic peptide, which reduced the blood pressure of hypertensive mice to the normal physiologic range. Seamless control of therapeutic transgenes by subconscious behavior may provide opportunities for treatment strategies of the future.

Aylett C.H.S.,ETH Zurich | Sauer E.,University of Basel | Imseng S.,University of Basel | Boehringer D.,ETH Zurich | And 3 more authors.
Science | Year: 2016

Target of rapamycin (TOR), a conserved protein kinase and central controller of cell growth, functions in two structurally and functionally distinct complexes: TORC1 and TORC2. Dysregulation of mammalian TOR (mTOR) signaling is implicated in pathologies that include diabetes, cancer, and neurodegeneration.We resolved the architecture of human mTORC1 (mTOR with subunits Raptor and mLST8) bound to FK506 binding protein (FKBP)-rapamycin, by combining cryo-electron microscopy at 5.9 angstrom resolution with crystallographic studies of Chaetomium thermophilum Raptor at 4.3 angstromresolution.The structure explains how FKBP-rapamycin and architectural elements of mTORC1 limit access to the recessed active site. Consistent with a role in substrate recognition and delivery, the conserved amino-terminal domain of Raptor is juxtaposed to the kinase active site.

Urbaszek B.,INSA Toulouse | Marie X.,INSA Toulouse | Amand T.,INSA Toulouse | Krebs O.,CNRS Laboratory for Photonics and Nanostructures | And 4 more authors.
Reviews of Modern Physics | Year: 2013

The mesoscopic spin system formed by the 104-106 nuclear spins in a semiconductor quantum dot offers a unique setting for the study of many-body spin physics in the condensed matter. The dynamics of this system and its coupling to electron spins is fundamentally different from its bulk counterpart or the case of individual atoms due to increased fluctuations that result from reduced dimensions. In recent years, the interest in studying quantum-dot nuclear spin systems and their coupling to confined electron spins has been further fueled by its importance for possible quantum information processing applications. The fascinating nonlinear (quantum) dynamics of the coupled electron-nuclear spin system is universal in quantum dot optics and transport. In this article, experimental work performed over the last decade in studying this mesoscopic, coupled electron-nuclear spin system is reviewed. Here a special focus is on how optical addressing of electron spins can be exploited to manipulate and read out the quantum-dot nuclei. Particularly exciting recent developments in applying optical techniques to efficiently establish nonzero mean nuclear spin polarizations and using them to reduce intrinsic nuclear spin fluctuations are discussed. Both results critically influence the preservation of electron-spin coherence in quantum dots. This overall recently gained understanding of the quantum-dot nuclear spin system could enable exciting new research avenues such as experimental observations of spontaneous spin ordering or nonclassical behavior of the nuclear spin bath. © 2013 American Physical Society.

Kohler V.,University of Basel | Turner N.J.,University of Manchester
Chemical Communications | Year: 2014

The concurrent operation of multiple catalysts can lead to enhanced reaction features including (i) simultaneous linear multi-step transformations in a single reaction flask (ii) the control of intermediate equilibria (iii) stereoconvergent transformations (iv) rapid processing of labile reaction products. Enzymes occupy a prominent position for the development of such processes, due to their high potential compatibility with other biocatalysts. Genes for different enzymes can be co-expressed to reconstruct natural or construct artificial pathways and applied in the form of engineered whole cell biocatalysts to carry out complex transformations or, alternatively, the enzymes can be combined in vitro after isolation. Moreover, enzyme variants provide a wider substrate scope for a given reaction and often display altered selectivities and specificities. Man-made transition metal catalysts and engineered or artificial metalloenzymes also widen the range of reactivities and catalysed reactions that are potentially employable. Cascades for simultaneous cofactor or co-substrate regeneration or co-product removal are now firmly established. Many applications of more ambitious concurrent cascade catalysis are only just beginning to appear in the literature. The current review presents some of the most recent examples, with an emphasis on the combination of transition metal with enzymatic catalysis and aims to encourage researchers to contribute to this emerging field. © 2015 The Royal Society of Chemistry.

Leuzinger S.,ETH Zurich | Luo Y.,University of Oklahoma | Beier C.,Technical University of Denmark | Dieleman W.,University of Antwerp | And 2 more authors.
Trends in Ecology and Evolution | Year: 2011

In recent decades, many climate manipulation experiments have investigated biosphere responses to global change. These experiments typically examined effects of elevated atmospheric CO2, warming or drought (driver variables) on ecosystem processes such as the carbon and water cycle (response variables). Because experiments are inevitably constrained in the number of driver variables tested simultaneously, as well as in time and space, a key question is how results are scaled up to predict net ecosystem responses. In this review, we argue that there might be a general trend for the magnitude of the responses to decline with higher-order interactions, longer time periods and larger spatial scales. This means that on average, both positive and negative global change impacts on the biosphere might be dampened more than previously assumed. © 2011 Elsevier Ltd.

Rossger K.,ETH Zurich | Charpin-El-Hamri G.,Institut Universitaire de France | Fussenegger M.,ETH Zurich | Fussenegger M.,University of Basel
Nature Communications | Year: 2013

Diet-induced obesity is a lifestyle-associated medical condition that increases the risk of developing cardiovascular disease, type 2 diabetes and certain types of cancer. Here we report the design of a closed-loop genetic circuit that constantly monitors blood fatty acid levels in the setting of diet-associated hyperlipidemia and coordinates reversible and adjustable expression of the clinically licensed appetite-suppressing peptide hormone pramlintide. Grafting of the peroxisome proliferator-activated receptor-α onto the phloretin-responsive repressor TtgR produces a synthetic intracellular lipid-sensing receptor (LSR) that reversibly induces chimeric TtgR-specific promoters in a fatty acid-adjustable manner. Mice with diet-induced obesity in which microencapsulated cells engineered for LSR-driven expression of pramlintide are implanted show significant reduction in food consumption, blood lipid levels and body weight when put on a high-fat diet. Therapeutic designer circuits that monitor levels of pathologic metabolites and link these with the tailored expression of protein pharmaceuticals may provide new opportunities for the treatment of metabolic disorders. © 2013 Macmillan Publishers Limited. All rights reserved.

Marguerat S.,University College London | Schmidt A.,University of Basel | Codlin S.,University College London | Chen W.,Berlin Institute for Medical Systems Biology | And 3 more authors.
Cell | Year: 2012

Data on absolute molecule numbers will empower the modeling, understanding, and comparison of cellular functions and biological systems. We quantified transcriptomes and proteomes in fission yeast during cellular proliferation and quiescence. This rich resource provides the first comprehensive reference for all RNA and most protein concentrations in a eukaryote under two key physiological conditions. The integrated data set supports quantitative biology and affords unique insights into cell regulation. Although mRNAs are typically expressed in a narrow range above 1 copy/cell, most long, noncoding RNAs, except for a distinct subset, are tightly repressed below 1 copy/cell. Cell-cycle-regulated transcription tunes mRNA numbers to phase-specific requirements but can also bring about more switch-like expression. Proteins greatly exceed mRNAs in abundance and dynamic range, and concentrations are regulated to functional demands. Upon transition to quiescence, the proteome changes substantially, but, in stark contrast to mRNAs, proteins do not uniformly decrease but scale with cell volume. © 2012 Elsevier Inc.

Sawarkar R.,ETH Zurich | Paro R.,ETH Zurich | Paro R.,University of Basel
Developmental Cell | Year: 2010

The Polycomb group (PcG) system represses the transcription of important developmental regulators and perpetuates this repression across multiple cell divisions. Inputs from outside the cell can influence PcG function by recruiting additional chromatin factors to PcG-regulated loci or by downregulating the PcG genes themselves. These types of PcG system modulation allow context-dependent induction of genes during development, in cancer, and in response to changes in the environment. In this review, we outline instances where molecular players in this process have been recently identified, comparing and contrasting different ways in which derepression is achieved, and projecting directions for future research. © 2010 Elsevier Inc.

Fischer J.,University of Basel | Fischer J.,University of Regensburg | Loss D.,University of Basel
Physical Review Letters | Year: 2010

We theoretically investigate the spin dynamics of a heavy hole confined to an unstrained III-V semiconductor quantum dot and interacting with a narrowed nuclear-spin bath. We show that band hybridization leads to an exponential decay of hole-spin superpositions due to hyperfine-mediated nuclear pair flips, and that the accordant single-hole-spin decoherence time T2 can be tuned over many orders of magnitude by changing external parameters. In particular, we show that, under experimentally accessible conditions, it is possible to suppress hyperfine-mediated nuclear-pair-flip processes so strongly that hole-spin quantum dots may be operated beyond the "ultimate limitation" set by the hyperfine interaction which is present in other spin-qubit candidate systems. © 2010 The American Physical Society.

Schmidt F.I.,ETH Zurich | Bleck C.K.E.,University of Basel | Helenius A.,ETH Zurich | Mercer J.,ETH Zurich
EMBO Journal | Year: 2011

Vaccinia virus (VACV), the model poxvirus, produces two types of infectious particles: mature virions (MVs) and extracellular virions (EVs). EV particles possess two membranes and therefore require an unusual cellular entry mechanism. By a combination of fluorescence and electron microscopy as well as flow cytometry, we investigated the cellular processes that EVs required to infect HeLa cells. We found that EV particles were endocytosed, and that internalization and infection depended on actin rearrangements, activity of Na+/H+ exchangers, and signalling events typical for the macropinocytic mechanism of endocytosis. To promote their internalization, EVs were capable of actively triggering macropinocytosis. EV infection also required vacuolar acidification, and acid exposure in endocytic vacuoles was needed to disrupt the outer EV membrane. Once exposed, the underlying MV-like particle presumably fused its single membrane with the limiting vacuolar membrane. Release of the viral core into the host cell cytosol allowed for productive infection. © 2011 European Molecular Biology Organization | All Rights Reserved.

Sawarkar R.,ETH Zurich | Paro R.,ETH Zurich | Paro R.,University of Basel
Trends in Cell Biology | Year: 2013

The molecular chaperone heat-shock protein of 90 kDa (Hsp90) stabilizes various proteins and occupies a central position in cellular networks. Hsp90 inhibitors are being tested in clinical trials as anticancer drugs. Recent studies have illuminated the unappreciated significance of this chaperone in chromatin transactions and this review focuses on its role in gene expression. By comparing the different mechanisms by which Hsp90 orchestrates transcriptional regulation, the review outlines the contributions of this function to the cellular and organismal phenotype. We chart exciting avenues for research to gain comprehensive insights in the chaperone's importance in cellular physiology, thereby presenting novel opportunities for therapeutic intervention. © 2012 Elsevier Ltd.

Slack E.,ETH Zurich | Balmer M.L.,University of Basel | Macpherson A.J.,University of Bern
Immunological Reviews | Year: 2014

Mutualism with our intestinal microbiota is a prerequisite for healthy existence. This requires physical separation of the majority of the microbiota from the host (by secreted antimicrobials, mucus, and the intestinal epithelium) and active immune control of the low numbers of microbes that overcome these physical and chemical barriers, even in healthy individuals. In this review, we address how B-cell responses to members of the intestinal microbiota form a robust network with mucus, epithelial integrity, follicular helper T cells, innate immunity, and gut-associated lymphoid tissues to maintain host-microbiota mutualism. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Struthers H.,ETH Zurich | Mindt T.L.,University of Basel | Schibli R.,ETH Zurich
Dalton Transactions | Year: 2010

The copper(I) catalyzed azide-alkyne cycloaddition (CuAAC) is the premier example of a click reaction. The reaction is modular, reliable and easy to perform, providing easy access to molecular diversity. The majority of reported applications of the reaction employ the 1,2,3-triazole as a stable linkage to connect two chemical/biological components, while the potential for metal coordination of the heterocycle itself has received much less attention. In fact, 1,4-functionalized 1,2,3-triazoles are versatile ligands offering several donor sites for metal coordination, including N3, N2 and C5. In this article, we summarize the areas in which the CuAAC has been applied to the synthesis of novel triazole-containing ligands for transition metals. © 2010 The Royal Society of Chemistry.

Poteryaev D.,University of Basel | Datta S.,Max Planck Institute of Molecular Cell Biology and Genetics | Ackema K.,University of Basel | Zerial M.,Max Planck Institute of Molecular Cell Biology and Genetics | Spang A.,University of Basel
Cell | Year: 2010

Sequential transport from early to late endosomes requires the coordinated activities of the small GTPases Rab5 and Rab7. The transition between early and late endosomes could be mediated either through transport carriers or by Rab conversion, a process in which the loss of Rab5 from an endosome occurs concomitantly to the acquisition of Rab7. We demonstrate that Rab conversion is the mechanism by which proteins pass from early to late endosomes in Caenorhabditis elegans coelomocytes. Moreover, we identified SAND-1/Mon1 as the critical switch for Rab conversion in metazoa. SAND-1 serves a dual role in this process. First, it interrupts the positive feedback loop of RAB-5 activation by displacing RABX-5 from endosomal membranes; second, it times the recruitment of RAB-7, probably through interaction with the HOPS complex to the same membranes. SAND-1/Mon1 thus acts as a switch by controlling the localization of RAB-5 and RAB-7 GEFs. © 2010 Elsevier Inc.

University of Basel and ETH Zurich | Date: 2015-11-17

The present invention refers to lipophilic extracts of members of the Iridaceae family, such as Iris germanica and/or Iris pallida, that have been found to promote lymphatic function. These extracts are suitable for the treatment of skin inflammation, rheumatoid arthritis, impaired wound healing, chronic inflammatory diseases, chronic airway inflammation, inflammatory bowel disease, rosacea, primary and/or secondary lymphedemas. The most active components were found to be the iridals.

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