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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.

Widmer A.F.,University of Basel
Journal of Hospital Infection | Year: 2013

Surgical hand hygiene is standard care prior to any surgical procedure. Per-operative glove punctures are observed in almost 30% of all interventions, and a risk factor for postoperative infections. In the past, washing hands with antimicrobial soap and water (surgical scrub) was the norm, mainly with chlorhexidine or iodine. More recently, alcohol-based hand rub has been successfully introduced, showing greater effectiveness, less irritation to the hands, and requiring less time than washing hands. All products should have a remnant effect that delays microbial growth under the gloved hand. Some of the alcohol-based compounds are effective (as determined by the European Norm EN 12791) within 90 s whereas others require 3-5 min, similar to the scrub. The short procedure relies heavily on proper technique and timing, since lowering the exposure time to <90 s leads to significantly lower effectiveness of bacterial killing. Today, surgical hand hygiene should meet EN 12791 in Europe, or other standards, such as the US Food and Drug Administration tentative final monograph norm in the USA. It is best performed by using an alcohol-based hand rub, but a scrub with chlorhexidine-containing soap also meets these standards. © 2013 The Healthcare Infection Society.

Stippich C.,University of Basel
Medical Radiology | Year: 2015

Functional magnetic resonance imaging (fMRI) provides noninvasive localisation and lateralisation of specificbrain functions by measuring local hemodynamic changes coupled to neuronal activation. Different magnetic properties of oxygenated (diamagnetic) and deoxygenated (paramagnetic) hemoglobin are exploited to generate the blood oxygen level dependent (BOLD) contrast. Diffusion tensor magnetic resonance imaging (DTI) measures anisotropic (directional) diffusion of protons along myelinated fi bers and thereby provides detailed information on the white matter architecture. Specificwhite matter tracts can be reconstructed using diffusion tensor tractography (DTT). During the last two decades both novel MR-modalities have revolutionised the imaging research on human brain function and structural connectivity under physiological and pathological conditions. Task-based presurgical fMRI in patients with brain tumors or epilepsies represents the best established and validated clinical application. Essential cortical motor and language areas can be localised and the language dominant hemisphere can be determined prior to treatment. DTI and DTT provide complimentary data on important white matter connections, e.g., the pyramidal tract and arcuate fascicle. This imaging information is indispensible to establish the best possible treatment for each individual patient, and to achieve the ultimate goal of surgery: function preserving complete or most radical removal of the pathology. To this end fMRI and DTI are integrated meaningfully into functional neuronavigation. While promising, resting-state fMRI is currently still under initial clinical investigation. The responsible clinical application requires standardised imaging and data processing as well as a profound knowledge of the imaging techniques employed, the underlying functional neuroanatomy, physiology and pathology, neuroplastic alterations, influencing factors, artifacts, pitfalls, validity and limitations. Finally, information on other functional neuroimaging modalities and multimodal integration is essential. © Springer-Verlag Berlin Heidelberg 2015.

Today, the settlement site of Luokesa 1 (L1) lies under water at the northern edge of Lake Luokesa in the Baltic Uplands, south-eastern Lithuania. Its 60 cm-thick Late Bronze-Early Iron Age cultural layer lies on top of lake marl. During excavations in 2008 and 2009, core samples at L1 were taken for the purpose of multidisciplinary investigations. From this material, five on-site pollen diagrams were created in parallel with geo-archaeological investigations and the examination of the botanical macro-remains. Two of these cores mainly comprised the cultural layer, another two consisted largely of the underlying lake marl and the fifth contained primarily the transition from the lake marl to the cultural layer. The chronological sequence was established through 11 AMS dates. The woodland history, starting from the Late Atlantic period, was recorded. The Quercetum mixtum values are quite low in the Subboreal, with the coniferous forest consisting mainly of Pinus and, though significantly less, Picea. At the transition to the cultural layer (Subatlantic) the pollen curves are highly variable, showing peaks in the curves for Betula and Alnus. Pollen from aquatic plants is also present. Changes in riparian vegetation and turbulent sedimentation conditions are to be expected and can be explained by a drop in the water level. As L1 was located on damp ground at that time, water influxes alternating with dry episodes were observed. In the area around L1 the sedge belt was less pronounced, and riparian woodland extended all the way to the shores of the lake. Pollen analyses of four sheep/goat dung samples provide information on the grazing season and pasture location of these domestic animals. The paper also discusses layer formation processes such as water level fluctuations and hiatuses. © 2014 Springer-Verlag Berlin Heidelberg.

Magyari E.,University of Basel
Transport in Porous Media | Year: 2014

The heat transfer characteristics of two boundary layer flows past an isothermal plane surface adjacent to a saturated Darcy-Brinkman porous medium is compared to each other in this paper. The flows are driven either by a stretching of the adjacent plane boundary, or by an external pressure gradient. It is found that below a threshold value P̃r* of the modified Prandtl number P̃r, the Nussselt number in case of the pressure gradient-driven flow is larger than in case of the wall- driven flow, while for P̃r > P̃r* the flow driven by the moving wall provides a more efficient heat transfer mechanism. The dependence of P̃r* on the Darcy number is also discussed in detail. © 2014 Springer Science+Business Media Dordrecht.

The relationship between stomatal conductance (gs) and leaf water potential (Ψl) is key to the understanding of plant function under changing climate. The variability among tree species gave rise to selection towards either of two contrasting water management types: isohydric or anisohydric. This study explores the variability of gs to Ψl across tree species. Curves of gs(Ψl) were collected from the scientific literature for 70 woody plant species. The data set is comprised of angiosperm and gymnosperm species from all major forest biomes. The hypothesis that curves from different tree species diverge between isohydric and anisohydric behaviours was tested. Species-specific curves formed a continuum, rather than dichotomy between isohydric and anisohydric, as confirmed by distribution models. Alternatively, the water potential at 50% of the maximum gs (Ψgs50) was used to quantitatively compare between species. A major difference emerged among xylem anatomy classes whereby ring-porous species had higher absolute gs at Ψl < -2 MPa than diffuse-porous and coniferous species. A positive, linear correlation was shown between Ψgs50 and Ψl at 50% loss of xylem conductivity. The results suggest that stomatal sensitivity to leaf water potential strongly relates to xylem characteristics. The use of Ψgs50 offers a quantitative alternative to the current, yet biased, distinction between isohydric and anisohydric species. © 2014 British Ecological Society.

Spang A.,University of Basel
Traffic | Year: 2012

The DSL1 complex is a conserved tethering complex at the endoplasmic reticulum that recognizes Golgi-derived COPI vesicles and hands them over to the fusion machinery. The DSL1 complex is the simplest tethering complex of the complexes associated with tethering containing helical rods (CATCHR) family. CATCHR tethering complexes play a role at compartments along the exocytic and endocytic pathways. In this review, different functions of the DSL1 complex are discussed, some open questions with the seemingly straightforward picture are pointed out and alternative functions of the DSL1 complex members are mentioned. © 2012 John Wiley & Sons A/S.

Krauchi K.,University of Basel | Deboer T.,Leiden University
Frontiers in Bioscience | Year: 2010

The circadian distribution of vigilance states and body temperature changes are tightly coupled. The increase in heat loss at the end of the day is associated with increased ease to fall asleep. Experimental data show that warming the skin or the brain can increase sleep propensity, sleep consolidation, and the duration of sleep. Anatomical and neurophysiological studies show that the pre-opticanterior- hypothalamus (POAH) is the main integrator of sleep and thermoregulatory information. It integrates information on vigilance states, body temperature, and environmental temperature and influences vigilance states and body temperature in response. Animals that display daily torpor may be a valuable model to investigate the relationship between sleep and thermoregulation. During torpor these animals seem to apply similar strategies and physiological processes as humans during entrance into sleep, but in a more extreme way, providing an excellent opportunity to investigate these processes in more detail. More systematic investigations are needed to further our understanding of the relationship between sleep and thermoregulation, and may provide the basis to treat sleep disturbances with thermal strategies.

Schmied R.,University of Basel | Wesenberg J.H.,National University of Singapore | Leibfried D.,U.S. National Institute of Standards and Technology
New Journal of Physics | Year: 2011

We present a detailed study of quantum simulations of coupled spin systems in surface-electrode (SE) ion-trap arrays, and illustrate our findings with a proposed implementation of the hexagonal Kitaev model (Kitaev A 2006 Ann. Phys. 321 2). The effective (pseudo)spin interactions making up such quantum simulators are found to be proportional to the dipole-dipole interaction between the trapped ions, and are mediated by motion that can be driven by state-dependent forces. The precise forms of the trapping potentials and the interactions are derived in the presence of an SE and a cover electrode. These results are the starting point to derive an optimized SE geometry for trapping ions in the desired honeycomb lattice of Kitaev's model, where we design the dipole-dipole interactions in a way that allows for coupling all three bond types of the model simultaneously, without the need for time discretization. Finally, we propose a simple wire structure that can be incorporated into a microfabricated chip to generate localized state-dependent forces which drive the couplings prescribed by this particular model; such a wire structure should be adaptable to many other situations. © IOP Publishing Ltd and Deutsche Physikalische Gesellschaft.

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.

Rauscher T.,Center for Astrophysics Research | Rauscher T.,University of Basel
AIP Advances | Year: 2014

Nucleosynthesis beyond Fe poses additional challenges not encountered when studying astrophysical processes involving light nuclei. Astrophysical sites and conditions are not well known for some of the processes involved. On the nuclear physics side, different approaches are required, both in theory and experiment. The main differences and most important considerations are presented for a selection of nucleosynthesis processes and reactions, specifically the s-, r-, γ-, and νp-processes. Among the discussed issues are uncertainties in sites and production conditions, the difference between laboratory and stellar rates, reaction mechanisms, important transitions, thermal population of excited states, and uncertainty estimates for stellar rates. The utility and limitations of indirect experimental approaches are also addressed. The presentation should not be viewed as confining the discussed problems to the specific processes. The intention is to generally introduce the concepts and possible pitfalls along with some examples. Similar problems may apply to further astrophysical processes involving nuclei from the Fe region upward and/or at high plasma temperatures. The framework and strategies presented here are intended to aid the conception of future experimental and theoretical approaches. © 2014 Author(s).

Bumann D.,University of Basel
Journal of Proteomics | Year: 2010

Infectious diseases cause tremendous mortality and morbidity worldwide. Rising antimicrobial resistance and the lack of new drugs cause an increasingly alarming crisis in infectious disease control. New system-level approaches are likely to help understand complex host/pathogen interactions as a basis for rational development of novel antibiotics and vaccines. Proteome analysis of pathogens in infected tissues comprehensively reveals functionally relevant pathogen activities during infection. It also highlights potential targets for antimicrobial chemotherapy as well as promising antigens for vaccination. Integration of these data with complementary large-scale data helps to further prioritize candidates for in-depth experimental analysis. Here, I discuss some of these approaches with a special emphasis on the model pathogen Salmonella. © 2010 Elsevier B.V.

Bruchmuller K.,University of Basel | Margraf J.,Ruhr University Bochum | Schneider S.,Ruhr University Bochum
Journal of Consulting and Clinical Psychology | Year: 2012

Objective: Unresolved questions exist concerning diagnosis of ADHD. First, some studies suggest a potential overdiagnosis. Second, compared with the male-female ratio in the general population (3:1), many more boys receive ADHD treatment compared with girls (6-9:1). We hypothesized that this occurs because therapists do not adhere to Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) and International Classification of Diseases (10th rev.; ICD-10) criteria. Instead, we hypothesized that, in accordance with the representativeness heuristic, therapists might diagnose attention-deficit/ hyperactivity disorder (ADHD) if a patient resembles their concept of a prototypical ADHD child, leading therapists to overlook certain exclusion criteria. This may result in overdiagnosis. Furthermore, as ADHD is more frequent in males, a boy might be seen as a more prototypical ADHD child and might therefore receive an ADHD diagnosis more readily than a girl would. Method: We sent a case vignette to 1,000 child psychologists, psychiatrists, and social workers and asked them to give a diagnosis. Four versions of the vignette existed: Vignette 1 (ADHD) fulfilled all DSM-IV/ICD-10 criteria of ADHD. Vignettes 2-4 (non-ADHD) included several ADHD symptoms but stated other ADHD criteria were nonfulfilled. Therefore, an ADHD diagnosis could not be given. Furthermore, boy and girl versions of each vignette were created. Results: In Vignettes 2-4 (non-ADHD), 16.7% of therapists diagnosed ADHD. In the boy version of these vignettes, therapists diagnosed ADHD around 2 times more than they did with the girl vignettes. Conclusions: Therapists do not adhere strictly to diagnostic manuals. Our study suggests that overdiagnosis of ADHD occurs in clinical routine and that the patient's gender influences diagnosis considerably. Thorough diagnostic training might help therapists to avoid these biases. © 2011 American Psychological Association.

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.

The pathogenesis of elevated blood pressure and other cardiovascular risk factors in the population and their progression over time is still incompletely understood, especially in young and healthy adults. The genetic and phenotypic determinants of blood pressure and other cardiovascular risk factors (GAPP) study is a population-based prospective cohort study involving a representative sample of healthy adults aged 25-41 years in the Principality of Liechtenstein. Exclusion criteria are any cardiovascular disease, diabetes, obstructive sleep apnoea syndrome, daily intake of nonsteroidal anti-inflammatory drugs and a body mass index >35 kg/m2. Examinations include detailed assessment of personal, medical, lifestyle and nutritional factors, standardised assessment of weight, height and waist circumference, blood pressure measurement (clinic and 24-hour ambulatory monitoring), electrocardiography (12-lead and 24-hour Holter monitoring), bioimpedance analysis, blood, urinary and genetic sampling, spirometry and sleep pulse oximetry with nasal flow measurement. Baseline examination is still ongoing. Follow-up examinations are scheduled every 3-5 years. Since June 2010, 1,333 participants have been enrolled. Mean age of the participants was 36.7 ± 4.9 years and 47.5% of all participants were male. Mean body mass index was 26.1 ± 3.1 kg/m2 in men and 23.5 ± 3.9 kg/m2 in women. The prevalence of hypertension and prediabetes was 24.7% and 32.1% in men and 6% and 23% in women respectively. Mean LDL levels were 3.34 ± 0.9 mmol/l in men and 2.75 ± 0.7 mmol/l in women. Median hsCRP was 0.9 (0.5; 1.8) mg/l with no gender differences. GAPP affords an excellent opportunity to assess genetic and phenotypic predictors of cardiovascular risk factors and their progression over time in young and healthy adults from the general population.

OBJECTIVE: To evaluate the usability of a variable square pulse (VSP) erbium-doped yttrium aluminium garnet (Er:YAG) laser for a lateral access osteotomy to the maxillary sinus in the course of a sinus elevation procedure. MATERIALS AND METHODS: In six formalin-fixed human heads and six fresh sheep heads, a VSP Er:YAG laser was used to perform a bilateral maxillary access osteotomy. For the osteotomies, the Er:YAG laser was applied with a pulse energy of 1000 mJ, a pulse duration of 300 mus, and a frequency of 12 Hz. The spot size was 0.9 mm, and the handpiece was kept approximately 10 mm from the bone surface. RESULTS: In all 24 sites investigated, the Er:YAG laser osteotomy was possible without any visible carbonization or thermal damage. The average time required for laser osteotomy for 12 standardized rectangular lateral windows in human cadavers was 39 s. No anatomical structures limited laser osteotomy, yet a critical evaluation of any membrane perforations was not possible because the postmortem fixation method caused partial detachment and fractional destruction. Laser-access osteotomy in six fresh sheep heads (12 sites) revealed major disruptions and perforations (<8 mm) of the sinus membrane (100%). CONCLUSION: Even though VSP Er:YAG laser osteotomy showed convincing results for efficient bone cutting without thermal damage, applied laser parameters do not seem to be practicable for any clinical sinus elevation procedure. Missing depth control resulted in uncontrollable severe damage of the underlying membrane.

Lyrer P.,University of Basel
Cochrane database of systematic reviews (Online) | Year: 2010

Extracranial internal carotid artery dissection (eICAD) is a leading cause of stroke in younger patients. 1. To determine whether, in patients with eICAD, treatment with anticoagulants, antiplatelet agents or control was associated with a better functional outcome. 2. To compare, among patients treated with either anticoagulants or antiplatelet agents, the risk of ischaemic strokes and major bleeding episodes. We searched the Cochrane Stroke Group Trials Register (last searched 3 October 2009). In addition, we performed comprehensive searches of the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2009), MEDLINE (January 1966 to November 2009) and EMBASE (January 1980 to November 2009), checked all relevant papers for additional eligible studies and contacted authors and researchers in the field. Randomised controlled trials, controlled clinical trials and non-randomised studies (if they reported on outcome stratified by antithrombotic treatment and included at least four patients) of anticoagulants or antiplatelet agents for the treatment of extracranial internal carotid artery dissection. Two review authors independently extracted data. Primary outcomes were death (all causes) and death or disability. Secondary outcomes were ischaemic stroke, symptomatic intracranial haemorrhage, and major extracranial haemorrhage during the reported follow-up period. The first choice treatment was taken for analyses. We did not find any completed randomised trials. Comparing antiplatelets with anticoagulants across 36 observational studies (1285 patients), there were no significant differences in the odds of death (Peto odds ratio (Peto OR) 2.02, 95% CI 0.62 to 6.60), or the occurrence of ischaemic stroke (OR 0.63, 95% CI 0.21 to 1.86) (34 studies, 1262 patients). For the outcome of death or disability, there was a non-significant trend in favour of anticoagulants (OR 1.77, 95% CI 0.98 to 3.22; P = 0.06) (26 studies, 463 patients). Symptomatic intracranial haemorrhages (5/627; 0.8%) and major extracranial haemorrhages (7/425; 1.6%) occurred only in the anticoagulation group; however, for both these outcomes, the estimates were imprecise and indicated no significant difference between the two treatment modalities. There were no randomised trials comparing either anticoagulants or antiplatelet drugs with control, thus there is no evidence to support their routine use for the treatment of extracranial internal carotid artery dissection. There were also no randomised trials that directly compared anticoagulants with antiplatelet drugs and the reported non-randomised studies did not show any evidence of a significant difference between the two.

Jacob F.,University of Basel
British Journal of Cancer | Year: 2014

Background:The level of plasma-derived naturally circulating anti-glycan antibodies (AGA) to P1 trisaccharide has previously been shown to significantly discriminate between ovarian cancer patients and healthy women. Here we aim to identify the Ig class that causes this discrimination, to identify on cancer cells the corresponding P1 antigen recognised by circulating anti-P1 antibodies and to shed light into the possible function of this glycosphingolipid.Methods:An independent Australian cohort was assessed for the presence of anti-P1 IgG and IgM class antibodies using suspension array. Monoclonal and human derived anti-glycan antibodies were verified using three independent glycan-based immunoassays and flow cytometry-based inhibition assay. The P1 antigen was detected by LC-MS/MS and flow cytometry. FACS-sorted cell lines were studied on the cellular migration by colorimetric assay and real-time measurement using xCELLigence system.Results:Here we show in a second independent cohort (n=155) that the discrimination of cancer patients is mediated by the IgM class of anti-P1 antibodies (P=0.0002). The presence of corresponding antigen P1 and structurally related epitopes in fresh tissue specimens and cultured cancer cells is demonstrated. We further link the antibody and antigen (P1) by showing that human naturally circulating and affinity-purified anti-P1 IgM isolated from patients ascites can bind to naturally expressed P1 on the cell surface of ovarian cancer cells. Cell-sorted IGROV1 was used to obtain two study subpopulations (P1-high, 66.1%; and P1-low, 33.3%) and observed that cells expressing high P1-levels migrate significantly faster than those with low P1-levels.Conclusions:This is the first report showing that P1 antigen, known to be expressed on erythrocytes only, is also present on ovarian cancer cells. This suggests that P1 is a novel tumour-associated carbohydrate antigen recognised by the immune system in patients and may have a role in cell migration. The clinical value of our data may be both diagnostic and prognostic; patients with low anti-P1 IgM antibodies present with a more aggressive phenotype and earlier relapse.British Journal of Cancer advance online publication, 28 August 2014; doi:10.1038/bjc.2014.455 www.bjcancer.com.

Tran-Van A.-F.,University of Basel | Wegner H.A.,Justus Liebig University
Beilstein Journal of Nanotechnology | Year: 2014

The research of cycloparaphenylenes (CPPs), the smallest armchair carbon nanotube, has been a quest for the past decades which experienced a revival in 2008 when the first synthesis was achieved. Since then CPPs with various ring sizes have been realized. The incorporation of substituents and the synthesis of CPPs with building blocks different from phenyl rings bear challenges of their own. Such structures, however, are highly interesting, as they allow for an incorporation of CPPs as defined nano-objects for other applications. Therefore, this review provides a status report about the current efforts in synthesizing CPPs beyond the parent unsubstituted oligo-phenylene structure. © 2014 Tran-Van and Wegner.

Baumhoer D.,University of Basel
Journal of Hand Surgery: European Volume | Year: 2010

Malignant bone tumours of the hands are uncommon. Although almost all lesions that occur in other parts of the skeleton can also affect the hands, their frequency, distribution and clinical characteristics differ. This review focusses on the histology of these tumours and gives an overview of the main differential diagnoses. Close correlation to radiologic and clinical features usually leads to the correct diagnosis. © 2010 The Author(s).

Wenger O.S.,University of Basel
Coordination Chemistry Reviews | Year: 2015

The field of excited-state proton-coupled electron transfer (PCET) with d6 metal complexes is reviewed. This includes mostly work on Ru(α-diimine)3 2+ complexes and rhenium(I) tricarbonyl diimines. In many cases the metal complexes were designed such that they can exhibit acid/base chemistry in addition to their well-known photoredox behavior. Upon photoexcitation the resulting complexes can then act either as combined electron/proton donors or as combined electron/proton acceptors. This review aims to illustrate the usefulness of such complexes for mechanistic studies of excited-state PCET. In other studies the photoactive d6 metal complexes merely act as ordinary electron donors or acceptors, but their reaction partners undergo PCET chemistry, i.e., they release a proton upon oxidation or they are protonated in the course of reduction. This design principle permits the investigation of long-range electron transfer which is coupled to proton transfer, for example in phenol-ruthenium(II) or phenol-rhenium(I) dyads, and this represents another focal point of this review. PCET is an elementary reaction step in biological photosynthesis and plays an important role in water oxidation as well as in CO2 reduction or N2 fixation. Mechanistic studies of excited-state PCET are therefore of interest in the greater contexts of solar energy conversion and small molecule activation. © 2014 Elsevier B.V.

Munsch S.,University of Fribourg | Meyer A.H.,University of Basel | Biedert E.,University of Fribourg
Behaviour Research and Therapy | Year: 2012

Objective: The aim of the study was to assess the long-term efficacy of Cognitive-Behavioral Treatment (CBT) and Behavioral Weight-Loss-Treatment (BWLT) in patients with binge eating disorder (BED) and to identify potential predictors of long-term treatment success. Method: In a sample of overweight to obese BED patients from a randomized comparative trial we evaluated the efficacy of four months of CBT or BWLT, followed by 12 months extended care, and a final follow-up assessment 6 years after the end of active treatment. Outcomes included binge eating, eating disorder pathology, depressive feelings, and body mass index. Results: After a strong improvement during active treatment, outcomes worsened during follow-up, yet remained improved at 6-year follow-up relative to pretreatment values. Long-term effects between CBT and BWLT were comparable. Rapid response during the early treatment phase was the only characteristic that was predictive of favorable treatment outcome in the long term. Conclusions: Both CBT and BWLT can be considered to be comparably efficacious in the long-term. Patients not responding strongly enough during the first four therapy sessions might be in need of tailored interventions early during the treatment phase. © 2012.

Sebranek J.J.,University of Wisconsin - Madison | Lugli A.K.,University of Basel | Coursin D.B.,University of Wisconsin - Madison
British Journal of Anaesthesia | Year: 2013

The prevalence of type 2 diabetes mellitus and the potential for perioperative dysglycaemia (hyperglycaemia, hypoglycaemia, stress-induced hyperglycaemia, or glucose variability) continue to increase dramatically. The majority of investigations on perioperative glycaemic control focused on critically ill patients and concentrated on goals of therapy, level of intensity of insulin infusion, feeding regimes, concerns over hypoglycaemia, and promulgation of recent guidelines calling for less strict glucose control. Areas of perioperative glycaemic control that deserve further investigation include preoperative identification of patients with undiagnosed type 2 diabetes and other forms of dysglycaemia, determination of appropriate intraoperative glucose goals, and establishment of the impact and natural history of perioperative abnormalities in glucose homeostasis. In the heterogeneous adult perioperative population, it is unlikely that one standard of perioperative glycaemic control is appropriate for all patients. This review presents recent evidence and expert guidance to aid preoperative assessment, intraoperative management, and postoperative care of the dysglycaemic adult patient. © 2013 © The Author [2013]. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

To quantify the overall effects of bariatric surgery compared with non-surgical treatment for obesity. Systematic review and meta-analysis based on a random effects model. Searches of Medline, Embase, and the Cochrane Library from their inception to December 2012 regardless of language or publication status. Eligible studies were randomised controlled trials with ≥ 6 months of follow-up that included individuals with a body mass index ≥ 30, compared current bariatric surgery techniques with non-surgical treatment, and reported on body weight, cardiovascular risk factors, quality of life, or adverse events. The meta-analysis included 11 studies with 796 individuals (range of mean body mass index at baseline 30-52). Individuals allocated to bariatric surgery lost more body weight (mean difference -26 kg (95% confidence interval -31 to -21)) compared with non-surgical treatment, had a higher remission rate of type 2 diabetes (relative risk 22.1 (3.2 to 154.3) in a complete case analysis; 5.3 (1.8 to 15.8) in a conservative analysis assuming diabetes remission in all non-surgically treated individuals with missing data) and metabolic syndrome (relative risk 2.4 (1.6 to 3.6) in complete case analysis; 1.5 (0.9 to 2.3) in conservative analysis), greater improvements in quality of life and reductions in medicine use (no pooled data). Plasma triglyceride concentrations decreased more (mean difference -0.7 mmol/L (-1.0 to -0.4) and high density lipoprotein cholesterol concentrations increased more (mean difference 0.21 mmol/L (0.1 to 0.3)). Changes in blood pressure and total or low density lipoprotein cholesterol concentrations were not significantly different. There were no cardiovascular events or deaths reported after bariatric surgery. The most common adverse events after bariatric surgery were iron deficiency anaemia (15% of individuals undergoing malabsorptive bariatric surgery) and reoperations (8%). Compared with non-surgical treatment of obesity, bariatric surgery leads to greater body weight loss and higher remission rates of type 2 diabetes and metabolic syndrome. However, results are limited to two years of follow-up and based on a small number of studies and individuals. PROSPERO CRD42012003317 (www.crd.york.ac.uk/PROSPERO).

Imbach P.,University of Basel | Crowther M.,Mc Master University
New England Journal of Medicine | Year: 2011

A 26-year-old woman with a history of chronic primary immune thrombocytopenia presents for evaluation. Her condition was first diagnosed when she was 11 years of age. Her platelet count has typically been less than 10,000 per cubic millimeter. Her symptoms have not responded to glucocorticoids, and she has had only transient responses to intravenous immune globulin. Previous treatments have included a course of cyclosporine, a course of four doses of rituximab, and splenectomy. Her bleeding symptoms have consisted mainly of menorrhagia, resulting in iron-deficiency anemia. She is currently being treated with a thrombopoietin-receptor agonist, which has resulted in an increase in her platelet count to between 50,000 and 200,000 per cubic millimeter and resolution of her excessive menstrual bleeding, with normalization of her hemoglobin level after iron therapy. She is now inquiring about the long-term treatment of her condition. Copyright © 2011 Massachusetts Medical Society. All rights reserved.

Gratwohl A.,University of Basel
Bone Marrow Transplantation | Year: 2012

The European Group for Blood and Marrow Transplantation (EBMT) risk score provides a simple tool to assess instantly chances and risks of hematopoietic SCT(HSCT) for an individual patient pre-transplant. Five factors, age of the patient, stage of the disease, time from diagnosis, donor type and donor recipient gender combination augment risk for an individual patient with increasing score from 0 as best to 7 as worst in an additive way. The score holds for all acquired hematological disorders, for allogeneic and autologous HSCT (score 0-5), is independent of the HSCT technology and is valid for standard or reduced intensity conditioning. Survival is uniformly worse for older patients, transplanted in advanced disease stage after a long-time interval and with a mismatched donor than for younger patients, transplanted soon in early stage with a well matched donor. Additional risk factors such as performance score, CMV serostatus or cytokine polymorphisms improve prediction but to different extents for low or high-risk patients. Comparative assessment of disease risk and global pre-transplant risk should guide decisions for each patient with his/her specific disease between HSCT and a non-transplant approach and replace the traditional 'donor vs no donor' with such a risk-adapted individualized strategy. © 2012 Macmillan Publishers Limited All rights reserved.

Sadallah S.,University of Basel
Seminars in immunopathology | Year: 2011

Considerable progress has been made in recognizing microvesicles as important mediators of intercellular communication rather than irrelevant cell debris. Microvesicles released by budding directly from the cell membrane surface (i.e., ectocytosis) either spontaneously or in response to various stimuli are called shed vesicles or ectosomes. Ectosomes are rightside-out vesicles with cytosolic content, and they expose phosphatidylserine in the outer leaflet of their membrane. Depending on their cellular origin, ectosomes have been associated with a broad spectrum of biological activities. In the light of recent findings, we now know that ectosomes derived from polymorphonuclear leukocytes, erythrocytes, platelets, and tumor cells have profound effects on the innate immune system, as well as on the induction of the adaptive immunity, globally reprogramming cells such as macrophages or dendritic cells toward an immunosuppressive and possibly tolerogenic phenotype. Although the effects observed in the circulation are mainly procoagulant and pro-inflammatory, ectosomes might be anti-inflammatory/immunosuppressive in local inflammation.

Kuban P.,Academy of Sciences of the Czech Republic | Hauser P.C.,University of Basel
Electrophoresis | Year: 2011

An overview of the developments of capacitively coupled contactless conductivity detection in CE and related techniques over approximately the last 2 years is given. The method has seen strong growth, and diverse new applications are being reported. Besides more advanced techniques on conventional capillaries, these include further developments of detection on lab-on-chip devices as well as in miniaturized chromatographic systems and some methods not involving separations. An increasing number of reports are based on the now readily available commercial detectors, but, while few publications on fundamental studies have appeared recently, interesting new approaches on creating low cost devices have also appeared. © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Spang A.,University of Basel
Membranes | Year: 2015

The trans-Golgi network functions in the distribution of cargo into different transport vesicles that are destined to endosomes, lysosomes and the plasma membrane. Over the years, it has become clear that more than one transport pathway promotes plasma membrane localization of proteins. In spite of the importance of temporal and spatial control of protein localization at the plasma membrane, the regulation of sorting into and the formation of different transport containers are still poorly understood. In this review different transport pathways, with a special emphasis on exomer-dependent transport, and concepts of regulation and sorting at the TGN are discussed. © 2015 by the authors; licensee MDPI, Basel, Switzerland.

Poggio M.,University of Basel | Degen C.L.,Massachusetts Institute of Technology
Nanotechnology | Year: 2010

We review recent efforts to detect small numbers of nuclear spins using magnetic resonance force microscopy. Magnetic resonance force microscopy (MRFM) is a scanning probe technique that relies on the mechanical measurement of the weak magnetic force between a microscopic magnet and the magnetic moments in a sample. Spurred by the recent progress in fabricating ultrasensitive force detectors, MRFM has rapidly improved its capability over the last decade. Today it boasts a spin sensitivity that surpasses conventional, inductive nuclear magnetic resonance detectors by about eight orders of magnitude. In this review we touch on the origins of this technique and focus on its recent application to nanoscale nuclear spin ensembles, in particular on the imaging of nanoscale objects with a three-dimensional (3D) spatial resolution better than 10 nm. We consider the experimental advances driving this work and highlight the underlying physical principles and limitations of the method. Finally, we discuss the challenges that must be met in order to advance the technique towards single nuclear spin sensitivity - and perhaps - to 3D microscopy of molecules with atomic resolution. © 2010 IOP Publishing Ltd.

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.

Korner C.,University of Basel
Current Opinion in Plant Biology | Year: 2015

For plants to grow they need resources and appropriate conditions that these resources are converted into biomass. While acknowledging the importance of co-drivers, the classical view is still that carbon, that is, photosynthetic CO2 uptake, ranks above any other drivers of plant growth. Hence, theory and modelling of growth traditionally is carbon centric. Here, I suggest that this view is not reflecting reality, but emerged from the availability of methods and process understanding at leaf level. In most cases, poorly understood processes of tissue formation and cell growth are governing carbon demand, and thus, CO2 uptake. Carbon can only be converted into biomass to the extent chemical elements other than carbon, temperature or cell turgor permit. © 2015.

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.

In-Albon T.,University of Basel
Swiss medical weekly : official journal of the Swiss Society of Infectious Diseases, the Swiss Society of Internal Medicine, the Swiss Society of Pneumology | Year: 2010

Mental disorders emerge in childhood and adolescence and are important risk factors for mental disorders in adolescence and adulthood. Since paediatricians are typically the first to see children with psychological problems, the aim of this study was to obtain a survey of mental disorders of children in paediatric settings. 250 paediatricians completed a questionnaire especially developed for this study, which asked for the estimated frequency and type of mental disorders in their patients, assurance in identifying mental disorders, diagnostic and treatment strategies used for these disorders and requests for training. Paediatricians estimated that 15% percent of children in their paediatric setting reported psychological difficulties. The most frequent mental disorders indicated by the paediatricians were attention-deficit hyperactivity disorder (ADHD), anxiety disorders, depression and aggressive disorders. Comfort in assigning diagnoses for anxiety disorders and depression was lower than for externalizing disorders. Counselling was the treatment approach most often reported in treating mental disorders, followed by psychopharmacological medication. Psychotherapy, however, was reported very rarely. Paediatricians' wish for continuing education included diagnostics and screening instruments for psychological problems in childhood. Estimated prevalence rates reported by paediatricians are comparable with rates in epidemiological studies. As paediatricians are often confronted with psychological problems, they have the important role in recognising the early signs of mental problems.

Zurcher A.,University of Basel
Schweizer Monatsschrift für Zahnmedizin = Revue mensuelle suisse d'odonto-stomatologie = Rivista mensile svizzera di odontologia e stomatologia / SSO | Year: 2012

Halitosis or bad breath is a taboo subject that is a widespread problem in the general population. Causes of bad breath can be multifactorial and long time sufferers can be marred from deep psychological stress. Because nine out of ten cases have an oral cause, the initial inquiry should be with a dentist. In a retrospective study from February 2003 to February 2010, the halitosis clinic at the University of Basel analyzed data from 465 patient medical histories. Study objectives evaluated the causes of halitosis, gender distribution and treatment success. All patients reported to have suffered from bad breath. However, 82.7% were actually diagnosed as having halitosis. Within this group, 96.2% showed an oral etiology and 3.8% showed an extra-oral cause. Women suffered significantly more from psychogenic halitosis. Success rates of 92.6% subjectively and 94.5% objectively reflect the treatment success of the diagnostic and therapeutic concepts presented at the University of Basel halitosis clinic over a seven year period.

Lake Luokesa lies in the eastern part of Lithuania and is part of a region of lakes formed by the Scandinavian ice-sheet and its melt waters during the last glaciation. During the Late Bronze-Early Iron Age transition, between 625 and 535 cal BC, a lakeside settlement with an onshore palisade was built on the platform of a carbonate bank. A total of five profiles, each comprising an organic occupation layer and lake sediments at its bottom and top, were examined micromorphologically. In this paper, natural and anthropogenic processes that led to the formation of the individual layers are presented; their possible origins are reconstructed and then discussed and compared to lakeside settlements of the circum-alpine region. This includes the emergence of lake marl, accumulation of organic layers in the settlement area as well as their decomposition, erosion and trampling features and inwash of sand through runoff from the hinterland. Due to the accumulation of the up to 60 cm thick culture layers in waterlogged environments, indications of seasonal deposition cycles could be identified. © 2014 Springer-Verlag Berlin Heidelberg.

Prehistoric agriculture and vegetation in Lithuania have so far been reconstructed largely using palynological data. This paper reports the archaeobotanical investigation of macroremains from the Late Bronze-early Iron Age (LBA-EIA) lakeside settlement Luokesa 1 (L1) in eastern Lithuania, with the aim of elucidating the settlement's history and crop diversity. The single phase settlement was fortified with an onshore palisade and is dated between 625 and 535 cal. bc. Samples were taken along a land to lake transect, and in the centre of L1. The stratigraphy consisted of three distinct layers: lake marl, cultural deposit and sandy limnic sediment on top. The plant spectrum shows that L1 was constructed on an exposed morainic shoal. It was surrounded by woodland, meadows, fields/gardens, ruderal habitats and riverine vegetation. Accumulated cultural deposits consisted mainly of manure (litter, fodder and dung of sheep/goat), with rubbish, sweepings from the houses or remains of the on-site vegetation. The crops were Panicum miliaceum, Triticum spelta, T. dicoccon, Hordeum vulgare s.l., Pisum sativum and Camelina sativa, the latter being the first prehistoric evidence in Lithuania. The trophic state of the lake increased during the occupation period. After the abandonment of the settlement the ruins decayed until the lake flooded the site. The results are discussed in a broader context of the LBA/EIA cultures in northern Central Europe. © 2014 Springer-Verlag Berlin Heidelberg.

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.

Bollhalder L.,University of Zurich | Pfeil A.M.,University of Basel | Tomonaga Y.,University of Zurich | Schwenkglenks M.,University of Zurich
Clinical Nutrition | Year: 2013

Background & aims: Glutamine supplementation has been associated with reduced mortality, infections and hospital length of stay in critically ill patients and patients undergoing major surgery. We carried out a meta-analysis to examine randomized clinical trial (RCT)-based evidence of these effects. Methods: Based on a systematic database search, RCTs published since 1990 were included if they evaluated the effect of parenteral glutamine supplementation against a background of parenteral nutrition. Enteral (tube) feeding in a proportion of patients was allowable. Information on RCT methodology, quality and outcomes was extracted. Random effects meta-analysis followed the DerSimonian-Laird approach. Results: Forty RCTs were eligible for meta-analysis. Parenteral glutamine supplementation was associated with a non-significant 11% reduction in short-term mortality (RR = 0.89; 95% CI, 0.77-1.04). Infections were significantly reduced (RR = 0.83; 95% CI, 0.72-0.95) and length of stay was 2.35 days shorter (95% CI, -3.68 to -1.02) in the glutamine arms. Meta-analysis results were strongly influenced by one recent trial. An element of publication bias could not be excluded. Conclusion: Parenteral glutamine supplementation in severely ill patients may reduce infections, length of stay and mortality, but substantial uncertainty remains. Unlike previous meta-analyses, we could not demonstrate a significant reduction in mortality. © 2012 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism.

Rentsch K.M.,University of Basel
TrAC - Trends in Analytical Chemistry | Year: 2016

Liquid chromatography coupled to mass spectrometry (LC-MS) is nowadays an indispensable tool in the clinical toxicology laboratory. It allows the identification of a very high number of compounds for confirmation of positive immunoassay results as well as the detection of yet unknown compounds present in an intoxicated patient. In clinical toxicological laboratories ion traps and triple stage quadrupole instruments are widely used, whereas high-resolution instruments are only used in specialized laboratories. As every analytical method also LC-MS has its limitations; the most important drawbacks are matrix effects which can lead to ionization enhancement or suppression. For the identification of a compound, 3 to 4 identification points are necessary, regardless if a high-resolution instrument is used or not. © 2016 Elsevier B.V.

Leyhe T.,University of Basel | Mussig K.,Heinrich Heine University Dusseldorf
Brain, Behavior, and Immunity | Year: 2014

Hashimoto's thyroiditis (HT) is the most frequent cause of hypothyroidism in areas with sufficient iodine intake. While the impact of thyroid function on mood and cognition is well known, only in the recent years, an increasing number of studies report on the association of HT with cognitive and affective disturbances also in the euthyroid state. Recent imaging studies have shown that these impairments are accompanied by altered brain perfusion, in particular, in the frontal lobe and a reduced gray matter density in the left inferior gyrus frontalis. Brain function abnormalities in euthyroid patients with HT may be subtle and only detected by specific testing or even severe as it is the case in the rare neuropsychiatric disorder Hashimoto's encephalopathy (HE). The good response to glucocorticoids in patients with HE indicates an autoimmune origin. In line with this, the cognitive deficits and the high psycho-social burden in euthyroid HT patients without apparent signs of encephalopathy appear to be associated with anti-thyroid peroxidase auto-antibody (TPO Abs) levels. Though in vitro studies showing binding of TPO Abs to human cerebellar astrocytes point to a potential direct role of TPO Abs in the pathogenesis of brain abnormalities in HT patients, TPO Abs may function only as a marker of an autoimmune disorder of the central nervous system. In line with this, anti-central nervous system auto-antibodies (CNS Abs) which are markedly increased in patients with HT disturb myelinogenesis in vitro and, therefore, may impair myelin sheath integrity. In addition, in HT patients, production of monocyte- and T-lymphocyte-derived cytokines is also markedly increased which may negatively affect multiple neurotransmitters and, consequently, diverse brain neurocircuits. © 2014 Elsevier Inc.

Rauscher T.,University of Basel
Astrophysical Journal, Supplement Series | Year: 2012

Sensitivities of nuclear reaction rates to a variation of nuclear properties are studied. Target nuclei range from proton- to neutron dripline for 10 ≤ Z ≤ 83. Reactions considered are nucleon- and α-induced reactions mediated by strong interaction. The contribution of reactions occurring on the target ground state to the total stellar rate is also given. General dependencies on various input quantities are discussed. Additionally, sensitivities of laboratory cross-sections of nucleon-, α-, and γ-induced reactions are shown, allowing us to estimate the impact of cross-section measurements. Finally, recommended procedures to explore and improve reaction rate uncertainties using the present sensitivity data are outlined. © © 2012. The American Astronomical Society. All rights reserved.

A general formalism to include experimental reaction cross sections into calculations of stellar rates is presented. It also allows us to assess the maximally possible reduction of uncertainties in the stellar rates by experiments. As an example for the application of the procedure, stellar neutron capture reactivities from KADoNiS v0.3 are revised and the remaining uncertainties shown. Many of the uncertainties in the stellar rates are larger than those obtained experimentally. This has important consequences for s-process models and the interpretation of meteoritic data because it allows the rates of some reactions to vary within a larger range than previously assumed. © 2012. The American Astronomical Society. All rights reserved.

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.

Tyndall A.,University of Basel
Nature Reviews Rheumatology | Year: 2014

Mesenchymal stem cells (MSCs) represent a heterogeneous progenitor cell population derived from various sources, including bone marrow, placental and adipose tissues. These cell populations are being extensively investigated for their regenerative, immunomodulatory and tissue-protective properties, and the therapeutic potential of MSCs is officially being tested in patients suffering from ischaemic, inflammatory, autoimmune and degenerative disorders. Unofficially, hundreds of centres worldwide already offer MSCs as a 'miracle' panacea treatment for almost every known human disease. Data from in vitro and animal models suggest that MSCs administered either locally or systemically are able to home to stressed tissue and indeed deliver a protective effect via predominately paracrine factors. Furthermore, dozens of published uncontrolled clinical trials have demonstrated strikingly positive therapeutic effects of MSCs with little acute toxicity; however, no prospective controlled trials have yet confirmed these findings, with the exception of one randomized controlled trial in renal transplantation. Thus, large prospective controlled trials are urgently needed to better understand MSC-based therapies and define their potential utility in the treatment of rheumatic diseases. Herein, I provide my opinions regarding the progress of MSC therapies to date and highlight issues that need to be addressed in the future. © 2014 Macmillan Publishers Limited. All rights reserved.

Podani J.,Hungarian Academy of Sciences | Schmera D.,University of Basel | Schmera D.,Balaton Limnological Research Institute
Ecography | Year: 2012

This paper deals with nestedness measures that are based on pairwise comparisons of sites, evaluates their performance and suggests improvements and generalizations. There are several conceptual and technical criteria to judge their ecological applicability. It is of primary concern whether the measures 1) have a clear mathematical definition, 2) are influenced by the ordering of the data matrix, 3) incorporate similarity alone or similarity together with a dissimilarity component, 4) consider site pairs with identical species number negatively or positively, 5) show sensitivity to small changes in the data, and 6) are not vulnerable to type I and type II error rates. We performed a detailed comparison of the nestedness metric based on overlap and decreasing fill (NODF), the percentage relativized nestedness and the percentage relativized strict nestedness functions (PRN and PRSN, respectively), based on analytical results as well as on artificial and actual examples. We show that NODF is in fact the average Simpson similarity of sites with different species totals, and that its value depends on how the matrix is actually ordered. NODF is modified to always produce the maximum possible result (NODF max), independently of the order of columns and rows. Being based on similarities, NODF and NODF max overemphasize the overlap component of nestedness and underrate richness difference which is also an important constituent of nested pattern in meta-community data. This latter feature is reflected adequately by PRN and PRSN. However, PRSN is similar to NODF and NODF max in sharing the disadvantages that 1) complete agreement and segregation in species composition are not distinguished, 2) a random matrix can have a higher value than truly nested patterns, and 3) they are ill-conditioned statistically. These problems are rooted mostly in that site pairs with tied totals affect the result negatively. We emphasize that PRN is free from these difficulties. PRN, PRSN, and NODF max, together with mean Simpson similarity exhibit highly similar statistical performance: they are resistant to type I and type II errors for the less constrained null models, although there are subtle differences depending on matrix fill and algorithm of randomization. The most constrained null model, with all marginal totals fixed, makes all statistics more sensitive to type I errors, although vulnerability depends greatly on matrix fill. © 2012 The Authors.

Bucher E.,University of Basel | Reinders J.,DuPont Pioneer | Mirouze M.,Montpellier University
Current Opinion in Plant Biology | Year: 2012

The mobility of genetic elements called transposable elements (TEs) was discovered half a century ago by Barbara McClintock. Although she had recognized them as chromosomal controlling elements, for much of the consequent time TEs were primarily considered as parasites of the host genome. However the recent explosion of discoveries in the fields of genomics and epigenetics have unambiguously shown the importance of TEs in genome function and evolution. Bursts of endogenous TEs have been reported in plants with epigenetic misregulation, revealing the molecular mechanisms underlying their control. We review here the different steps in TE invasion of the host genome involving epigenetic control and environmental stress responses. As TEs propagate in plant genomes and attract epigenetic marks, their neo-insertions can lead to the formation of new, heritable epigenetic variants (epialleles) of genes in their vicinity and impact on host gene regulatory networks. The epigenetic interplay between TE and genes thus plays a crucial role in the TE-host co-evolution. © 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.

Tserkovnyak Y.,University of California at Los Angeles | Loss D.,University of Basel
Physical Review A - Atomic, Molecular, and Optical Physics | Year: 2011

It is shown that anisotropic spin chains with gapped bulk excitations and magnetically ordered ground states offer a promising platform for quantum computation, which bridges the conventional single-spin-based qubit concept with recently developed topological Majorana-based proposals. We show how to realize the single-qubit Hadamard, phase, and π/8 gates as well as the two-qubit controlled-not (cnot) gate, which together form a fault-tolerant universal set of quantum gates. The gates are implemented by judiciously controlling Ising exchange and magnetic fields along a network of spin chains, with each individual qubit furnished by a spin-chain segment. A subset of single-qubit operations is geometric in nature, relying on control of anisotropy of spin interactions rather than their strength. We contrast topological aspects of the anisotropic spin-chain networks to those of p-wave superconducting wires discussed in the literature. © 2011 American Physical Society.

Krusche B.,University of Basel
European Physical Journal: Special Topics | Year: 2011

Recent results for the photoproduction of mesons off nuclei are reviewed. These experiments have been performed for two major lines of research related to the properties of the strong interaction. The investigation of nucleon resonances requires light nuclei as targets for the extraction of the isospin composition of the electromagnetic excitations. This is done with quasi-free meson photoproduction off the bound neutron and supplemented with the measurement of coherent photoproduction reactions, serving as spin and/or isospin filters. Furthermore, photoproduction from light and heavy nuclei is a very efficient tool for the study of the interactions of mesons with nuclear matter and the in-medium properties of hadrons. Experiments are currently rapidly developing due to the combination of high quality tagged (and polarized) photon beams with state-of-the-art 4π detectors and polarized targets. © 2011 EDP Sciences and Springer.

Hasler C.C.,University of Basel
Swiss Medical Weekly | Year: 2013

It is wrong to believe that back pain only burdens adults: the yearly incidence during growth ranges from 10-20%, continuously increasing from childhood to adolescence. Rapid growth-related muscular dysbalance and insufficiency, poor physical condition in an increasingly sedentary adolescent community or - vice versa - high level sports activities, account for the most prevalent functional pain syndromes. In contrast to adults the correlation of radiographic findings with pain is high: the younger the patient, the higher the probability to establish a rare morphologic cause such as benign or malignant tumours, congenital malformations and infections. In children younger than 5 years old, the likelihood is more than 50%. The following red flags should lower the threshold for a quick in-depth analysis of the problem: Age of the patient <5 years, acute trauma, functional limitation for daily activities, irradiating pain, loss of weight, duration >4 weeks, history of tumour, exposition to tuberculosis, night pain and fever. High level sport equals a biomechanical field test which reveals the biologic individual response of the growing spine to the sports-related forces. Symptomatic or asymptomatic inhibitory or stimulatory growth disturbances like Scheuermann disease, scoliosis or fatigue fractures represent the most frequent pathomorphologies. They usually occur at the disk-growth plate compound: intraspongious disk herniation, diminuition of anterior growth with vertebral wedging and apophyseal ring fractures often occur when the biomechanical impacts exceed the mechanical resistance of the cartilaginous endplates. Spondylolysis is a benign condition which rarely becomes symptomatic and responds well to conservative measures. Associated slippage of L5 on S1 is frequent but rarely progresses. The pubertal spinal growth spurt is the main risk factor for further slippage, whereas sports activity - even at a high level - is not. Therefore, the athlete should only be precluded from training if pain persists or in case of high grade slips. Perturbance of the sagittal profile with increase of lumbar lordosis, flattening of the thoracic spine and retroflexion of the pelvis with hamstrings contractures are strong signs for a grade IV olisthesis or spondyloptosis with subsequent lumbosacral kyphosis. Idiopathic scoliosis is not related to pain unless it is a marked (thoraco-) lumbar curve or if there is an underlying spinal cord pathology. Chronic back pain is an under recognised entity characterised by its duration (>3 months or recurrence within 3 months) and its social impacts such as isolation and absence from school or work. It represents an independent disease, uncoupled from any initial trigger. Multimodal therapeutic strategies are more successful than isolated, somatising orthopaedic treatment. Primary and secondary preventive active measures for the physically passive adolescents, regular sports medical check-up's for the young high level athletes, the awareness for the rare but potentially disastrous pathologies and the recognition of chronic pain syndromes are the cornerstones for successful treatment of back pain during growth.

Heininger U.,University of Basel
Pediatric Infectious Disease Journal | Year: 2012

Pertussis is a bacterial disease that is transmitted very efficiently from human to human by droplets. It occurs at any age, is endemic in any population, and can cause outbreaks in highly variable frequencies. Hallmark of the disease is cough with or without paroxysms, whoop, and vomiting. Diagnosis relies on clinical suspicion followed by laboratory confirmation (PCR, Serology) and should be followed by prompt antibiotic treatment to stop spread of the bacteria to contact persons. Control of pertussis by acellular vaccines is possible to some extent if immunization coverage is high and booster doses are given lifelong. However new vaccines with higher efficacy rates are warranted. © 2012 Lippincott Williams & Wilkins.

Buglione L.,Nanyang Technological University | Buglione L.,University of Basel | Pumera M.,Nanyang Technological University
Electrochemistry Communications | Year: 2012

There were many claims of synergic effect of carbon nanotubes and graphene leading to enhanced capacitance of the resulting composite. Here we show that "spacing" of graphene sheets with carbon nanotubes does not yield to any synergic effect of dramatically improved capacitance but in contrary, the resulting capacitance is merely arithmetic average of weight specific capacitances of the individual components. © 2012 Elsevier B.V.

4,2′:6′,4′′-Terpyridine (4,2′:6′, 4′′-tpy) is one of the less well documented isomers of the well-established bis-chelating 2,2′:6′,2′′-terpyridine. The N-donors of the outer rings in 4,2′:6′,4′′-tpy subtend an angle of 120°, leading to a description of 4,2′:6′, 4′′-tpy as a divergent ligand. Because it typically binds metal ions through the outer N-donors only, 4,2′:6′,4′′-tpy is an ideal linker for combination with metal nodes (often geometrically flexible d10 ions) in coordination polymers and metallomacrocyclic complexes. The facile functionalization of terpyridines in the 4′-position allows access to a suite of 4′-X-4,2′:6′,4′′-tpy ligands in which the 4′-substituent, X, can be selected to assist in directing the metal-ligand assembly process. This overview of recent advances in the chemistry of 4,2′:6′,4′′-tpy and its 4′-substituted derivatives looks at relationships within a series of chiral polymers, competition between the formation of metallocyclic complexes versus polymers, and the use of extended aryl systems to encourage the formation of coordination polymers in which π-stacking of arene domains dominates in the assembly process. Use of metal(ii) acetates is key to the formation of paddle-wheel and larger cluster nodes that direct the assembly of both predetermined and unexpected architectures. This journal is © the Partner Organisations 2014.

Zimmerli W.,University of Basel
New England Journal of Medicine | Year: 2010

A 57-year-old man presents with fever, chills, and new lumbar back pain 2 weeks after undergoing a prostate biopsy because of an increased prostate-specific antigen level. His temperature is 39.7°C; he has an enlarged, tender prostate and lumbar spine tenderness. His white-cell count is 9100 per cubic millimeter, and the C-reactive protein level is 343 mg per liter. Urine and blood cultures reveal multidrug-resistant, extended-spectrum β-lactamase-producing Escherichia coli susceptible to imipenem. How should he be evaluated and treated? Copyright © 2010 Massachusetts Medical Society. All rights reserved.

Baudouin S.J.,University of Basel | Baudouin S.J.,University of Cardiff
European Journal of Neuroscience | Year: 2014

Autism is a developmental disorder characterised by a high heterogeneity of clinical diagnoses and genetic associations. This heterogeneity is a challenge for the identification of the pathophysiology of the disease and for the development of new therapeutic strategies. New conceptual approaches are being used to try to challenge this complexity and gene cluster analysis studies suggest that the pathophysiology of autism is associated with a dysregulation of specific cellular mechanisms. This review will present the experimental evidence for a convergence of synaptic pathophysiology between syndromic and non-syndromic forms of autism, grouped under the generic term of autism spectrum disorders. In particular I will highlight the results from genetic mouse models identifying a convergence of dysregulation of the synaptic type I metabotropic glutamate receptor pathway in mouse models for autism spectrum disorders. These results help to build a new conceptual framework for the study of the synaptic phenotype of autism, which is important for the identification of new therapeutic strategies. © 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Donath M.Y.,University of Basel
Diabetologia | Year: 2016

The association between the metabolic syndrome and a pathological activation of the innate immune system is now well established. Thus, defective insulin secretion and action are due, at least in part, to islet, liver and fat inflammation in type 2 diabetes. Furthermore, an inflammatory process also seems to be involved in the development of cardiovascular, renal and ophthalmological complications of this disease. Interestingly, several other inflammatory diseases are associated with the metabolic syndrome, such as psoriasis, gout and rheumatic arthritis. The aim of this review is to discuss the clinical progress of anti-inflammatory drugs in the treatment of type 2 diabetes and then speculate on the possible further development of these drugs, with the aim of using the drugs in combination in order to combat the multiple manifestations of inflammatory diseases. This review summarises a presentation given at the ‘Islet inflammation in type 2 diabetes’ symposium at the 2015 annual meeting of the EASD. It is accompanied by two other reviews on topics from this symposium (by Simone Baltrusch, DOI: 10.1007/s00125-016-3891-x, and Jerry Nadler and colleagues, DOI: 10.1007/s00125-016-3890-y) and a commentary by the Session Chair, Piero Marchetti (DOI: 10.1007/s00125-016-3875-x). © 2016, Springer-Verlag Berlin Heidelberg.

Katan M.,University of Basel
Swiss medical weekly : official journal of the Swiss Society of Infectious Diseases, the Swiss Society of Internal Medicine, the Swiss Society of Pneumology | Year: 2010

Stress is defined as anything that throws the body out of homeostatic balance; for example an acute illness. Any stressor which activates the hypothalamo-pituitary-adrenal (HPA) axis leads to an increase in concentrations of the adrenal stress hormone, cortisol. One of the major hypothalamic stress hormones, which is stimulated by different stressors, is vasopressin (AVP). However, measurement of circulating AVP levels is challenging because it is released in a pulsatile pattern, it is unstable and is rapidly cleared from plasma. AVP derives from a larger precursor peptide (pre-provasopressin) along with copeptin which is released in an equimolar ratio to AVP and is more stable in the circulation and easy to determine. Copeptin levels were found to closely mirror the production of AVP. We have shown that copeptin more subtly mirrors the individual stress level compared to cortisol. Due to the positive association of copeptin with the severity of illness and outcome, copeptin has been proposed as a prognostic marker in acute illness. The prognostic accuracy of copeptin has been analysed in sepsis, pneumonia, lower respiratory tract infections, stroke and other acute illnesses. Thereby, copeptin was found to accurately mirror disease severity and to discriminate patients with unfavourable outcomes from patients with favourable outcomes. Copeptin improves the prognostic information provided by commonly used clinical scoring instruments. Importantly, interpretation of copeptin levels must always consider the clinical setting. An accurate prognostic assessment has the potential to guide interventions and effectively plan and monitor rehabilitation and, thus optimise the management of individual patients and the allocation of limited health care resources. Future intervention studies must prove the value of copeptin in clinical decision making and in improving the overall medical management of patients with acute illnesses.

Kuhne T.,University of Basel
Seminars in Hematology | Year: 2015

Chronic immune thrombocytopenia (ITP) occurs in approximately one fifth of children with primary ITP and is characterized by a significant lack of clinical data. A minority of these children exhibit bleeding and need treatment. Often standard therapy used for patients with newly diagnosed ITP is administered to stop bleeding and to increase the platelet count. These drugs are associated with adverse effects, which is particularly evident when used during long time. In adult patients with chronic ITP, thrombopoietin receptor agonists (TPO-RAs) demonstrated efficacy in approximately 80% of patients. These drugs have been studied intensely for registration purposes; however, for children and adolescents they are not yet approved and studies are ongoing. First experiences with these drugs show similar effects and safety as in adults, though based on very small numbers of children. These drugs have the potential to be used during long time, in order to increase platelets, to stop or prevent bleeding and to augment quality of life, making long-term safety an important issue. © 2014 Elsevier Inc.

Scharer L.,University of Basel
Philosophical transactions of the Royal Society of London. Series 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.

Berner D.,University of Basel
Ecology and Evolution | Year: 2012

A key goal in evolutionary quantitative genetics is to understand how evolutionary trajectories are constrained by pleiotropic coupling among multiple traits. Because studying pleiotropic constraints directly at the molecular genetic level remains very difficult, several analytical approaches attempt to draw conclusions about constraints by relating the orientation of the eigenvectors of the traits' (co)variance matrix to vectors of multivariate selection. On the basis of explicit models of genetic architecture, I here argue that the value of such approaches is greatly overestimated. The reason is that eigenvector orientation can be highly unstable and lack a biologically meaningful relationship with the underlying traits' genetic architecture. Genetic constraints are more profitably explored through experimental approaches avoiding the mathematical abstraction inherent in eigenanalysis.© 2012 The Author.

Cahenzli F.,University of Basel
Proceedings. Biological sciences / The Royal Society | Year: 2013

Twenty years ago, scientists began to recognize that parental effects are one of the most important influences on progeny phenotype. Consequently, it was postulated that herbivorous insects could produce progeny that are acclimatized to the host plant experienced by the parents to improve progeny fitness, because host plants vary greatly in quality and quantity, and can thus provide important cues about the resources encountered by the next generation. However, despite the possible profound implications for our understanding of host-use evolution of herbivores, host-race formation and sympatric speciation, intense research has been unable to verify transgenerational acclimatization in herbivore-host plant relationships. We reared Coenonympha pamphilus larvae in the parental generation (P) on high- and low-quality host plants, and reared the offspring (F(1)) of both treatments again on high- and low-quality plants. We tested not only for maternal effects, as most previous studies, but also for paternal effects. Our results show that parents experiencing predictive cues on their host plant can indeed adjust progeny's phenotype to anticipated host plant quality. Maternal effects affected female and male offspring, whereas paternal effects affected only male progeny. We here verify, for the first time to our knowledge, the long postulated transgenerational acclimatization in an herbivore-host plant interaction.

Wootton J.,University of Basel
Entropy | Year: 2015

Here we study an efficient algorithm for decoding topological codes. It is a simple form of HDRG decoder, which could be straightforwardly generalized to complex decoding problems. Specific results are obtained for the planar code with both i.i.d. and spatially correlated errors. The method is shown to compare well with existing ones, despite its simplicity. © 2015 by the authors.

Buttel A.E.,University of Basel
Schweizer Monatsschrift für Zahnmedizin = Revue mensuelle suisse d'odonto-stomatologie = Rivista mensile svizzera di odontologia e stomatologia / SSO | Year: 2012

Immediate loading of two unsplinted mandibular implants by means of an overdenture may be a viable and cost-effective treatment option to improve the patient's oral health-related quality of life. We therefore conducted a prospective observational study to estimate implant survival and patient satisfaction after an immediate loading protocol in edentulous patients. Twenty edentulous patients who received two interforaminal implants (Straumann Standard implant, length 12 mm) were included in our study. Immediately after implant placement, ball attachments with a diameter of 2.25 mm were placed on the implants and the respective matrices were directly incorporated in the existing complete denture. Clinical recalls were scheduled 1 week, 1, 3, 6 months, and 1 and 2 years after implant placement. The following clinical parameters were assessed: gingival bleeding index (GBI), visual plaque index (VPI), and soft tissue overgrowth. In addition, we also assessed radiological bone level change (RBLC) using panoramic radiographs, and patient satisfaction using a visual analogue scale at baseline, after 6 months and 2 years. No implant failures occurred during the 2-year observation period, resulting in a survival rate of 100%. The mean RBLC was 0.67 mm (95% Confidence Interval [95% CI]: 0.47-0.86 mm) two years after surgery. The GBI and VPI after two years were 24 (95% CI: 9-38)% and 36 (95% CI: 19-53)%, respectively. Soft tissue overgrowth was 1.6 mm (95% CI: 1.1-2.1) on average after two years. In a multivariate regression model, patients with a GBI ≥50% on average showed an increased RBLC (-0.6 mm, p = 0.007). High patient ratings were recorded for overall satisfaction. Overall patient satisfaction measured on a scale between one and ten was 5.2 (95% CI: 2.1-8.5) before implant placement and 9.5 (95% CI: 9.1-10) after 2 years. Immediate loading of two unsplinted interforaminal implants in overdenture patients using ball attachments is a clinically viable treatment option that leads to a high survival rate and oral health-related quality of life.

Schaad U.B.,University of Basel
World Journal of Pediatrics | Year: 2010

Background: This study was conducted to assess the efficacy of OM-85 BV (Broncho-Vaxom) in the prevention of pediatric recurrent respiratory tract infections (RTIs). Available evidence suggests that defining recurrent RTIs as ≥3 infections per fall-winter semester is both medically and epidemiologically justified. Therefore, this criterion was chosen as a primary endpoint. Methods: Trials were identified through consultation of bibliographic databases and other channels. Eleven non-blinded studies plus one dealing with primary prevention were excluded and eight randomized controlled trials were included in the meta-analysis. The data were compared at 6 months, which represented the end of most studies. The complete database was examined according to the guidelines of the Cochrane collaboration. Results: The mean age of children and the number of RTIs in the preceding year were comparable at admission. Of the patients in the OM-85 BV treated population (n=435), 32% had recurrent RTIs (that is, ≥3 RTIs/6 months) vs. 58.2% in the placebo treated population (n=416; P<0.001). Sensitivity analysis showed that this was not driven by any particular trial. The results of this review were also positive for the active treatment regarding the secondary variables, which were represented by the number of patients with at least one RTI and the mean number of RTIs. Conclusions: This meta-analysis shows, as observed in several individual trials, that the population treated with OM-85 BV had significantly and consistently fewer cases of recurrent RTIs. The data suggest that the effect is greater in patients at increased risk of recurrent RTIs. © 2010 World J Pediatr. All rights reserved.

Liang C.,University of Basel | Jansen T.L.C.,Zernike Institute for Advanced Materials
Journal of Physical Chemistry B | Year: 2013

We present the implementation of an approach to simulate the two-dimensional sum frequency generation response functions of systems with numerous coupled chromophores using a quantum-classical simulation scheme that was previously applied successfully to simulate two-dimensional infrared spectra. We apply the simulation to the amide I band of a mechanosensitive channel protein. By examining the signal generated from different segments of the protein, we find that the overall signal is impossible to interpret without the aid of simulations due to the interference of the response generated on different segments of the protein. We do not find significant cross-peaks in the spectra, even when the waiting time is increased. The spectra are thus not sensitive to coupling between different structural elements. Despite this, we conclude that two-dimensional sum frequency generation spectroscopy will be a powerful tool to investigate membrane bound proteins. © 2013 American Chemical Society.

There is no doubt about the strong association of malnutrition and adverse medical outcomes including mortality, morbidity and quality of life. Particularly in the elderly and frail medical inpatient population, loss of appetite due to the acute illness further aggravates nutritional status. In fact, this relationship between acute disease and eating behaviour / nutritional status may well be bidirectional, with not only illness affecting nutritional status, but also dietary factors influencing the course of illness. Whether loss of appetite associated with acute illness is indeed a protective physiological response or a therapeutic target needing early corrective nutritional therapy is a matter of current debate and can only be resolved within a large and well-designed randomised controlled trial comparing early nutritional therapy with "appetite-guided" nutrition in this patient population. Apart from in critical care, where various large trials have recently been published, there is an important lack of high quality data from large randomised trials in unselected acutely ill medical inpatients to support the early use of nutritional therapy, to shed light on the optimal type, caloric amount and timing of nutritional therapy and to answer ultimately the question as to which patient population will in fact benefit from nutritional interventions. Currently, the EFFORT trial is enrolling patients and aims to fill these literature gaps. The aim of this review is to discuss the current evidence regarding nutritional therapy in acutely ill medical inpatients, and to recommend whether or not, based on today's available evidence, physician should indeed encourage their malnourished patients to "...finish their lunch". © 2015, EMH Swiss Medical Publishers Ltd. All rights reserved.

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.

In a recent paper by Hamad and Pop (Transp Porous Med 2010) a comprehensive numerical study of the title problem has been reported. The goal of the present note is (i) to give exact analytical solutions of this model for some special cases of physical interest, and (ii) to point out that within the model considered by Hamad and Pop no essential distinguishing features between the convective heat transfer in nanofluids and in usual viscous fluids occur. © 2011 Springer Science+Business Media B.V.

Hruz P.,University of Basel
Digestive Diseases | Year: 2014

Eosinophilic esophagitis (EoE) is an allergy-associated disease defined clinically by esophagus-related symptoms in combination with a dense esophageal eosinophilia, both of which are unresponsive to prolonged acid suppression with proton pump inhibitors. Over the last two decades EoE has increasingly been recognized in various geographical areas (mostly industrialized countries) with high socioeconomic development. The prevalence rate is increasing and reaches up to 50 patients per 100,000 inhabitants in some indicator regions. Whether this increased prevalence is due to a real increase in incidence, a result of increased awareness by health care providers or because of the nonfatal nature of EoE adding more and more cases to the patient pool is still a matter of controversy. Several studies have consistently demonstrated a male predominance in EoE, with a male-to-female risk ratio of 3:1. The average age at diagnosis ranges between 30 and 50 years and suggests that EoE is a disease of the middle-aged man. It can affect patients of every race, but the disease is more common among Caucasians. In both children and adults, EoE has been clearly associated with allergies to food and aeroallergens, and most EoE patients present with a personal allergic background (e.g. asthma, rhinoconjunctivitis or oral allergy syndrome). In conclusion, knowledge of epidemiologic parameters of EoE is crucial for identifying risk factors as well as pathogenic mechanisms, planning preventive measures and determining optimal treatment strategies. © 2014 S. Karger AG, Basel.

Tsakiris D.A.,University of Basel
Seminars in Hematology | Year: 2014

Direct oral anticoagulants (DOACs) have been established and already registered for clinical use on a wide basis in the United States and Europe. Different from the vitamin K antagonists (VKA), their mode of action is based on the direct inhibition of the single coagulation enzymes factor Xa or IIa. Other laboratory tests of hemostasis, such as the global tests prothrombin time (PT/INR) and activated partial thromboplastin time (APTT), or various functional coagulation assays involving generation of factor Xa or IIa for their endpoints, can be negatively influenced by the presence of the anticoagulant in the test sample. This interference has been well documented for rivaroxaban, apixaban, and dabigatran and is most prominent during the first hours after intake of the respective agent. Thus, the potential influence of DOACs has always to be considered when interpreting abnormal functional coagulation assays. © 2014 Elsevier Inc.

Burmann B.M.,University of Bayreuth | Burmann B.M.,University of Basel | Knauer S.H.,University of Bayreuth | Sevostyanova A.,Ohio State University | And 5 more authors.
Cell | Year: 2012

NusG homologs regulate transcription and coupled processes in all living organisms. The Escherichia coli (E. coli) two-domain paralogs NusG and RfaH have conformationally identical N-terminal domains (NTDs) but dramatically different carboxy-terminal domains (CTDs), a β barrel in NusG and an α hairpin in RfaH. Both NTDs interact with elongating RNA polymerase (RNAP) to reduce pausing. In NusG, NTD and CTD are completely independent, and NusG-CTD interacts with termination factor Rho or ribosomal protein S10. In contrast, RfaH-CTD makes extensive contacts with RfaH-NTD to mask an RNAP-binding site therein. Upon RfaH interaction with its DNA target, the operon polarity suppressor (ops) DNA, RfaH-CTD is released, allowing RfaH-NTD to bind to RNAP. Here, we show that the released RfaH-CTD completely refolds from an all-α to an all-β conformation identical to that of NusG-CTD. As a consequence, RfaH-CTD binding to S10 is enabled and translation of RfaH-controlled operons is strongly potentiated. PaperFlick: © 2012 Elsevier Inc.

Cherchneff I.,University of Basel
Astronomy and Astrophysics | Year: 2012

Aims. We model the chemistry of the inner wind of the carbon star IRC+10216 and consider the effects of periodic shocks induced by the stellar pulsation on the gas to follow the non-equilibrium chemistry in the shocked gas layers. We consider a very complete set of chemical families, including hydrocarbons and aromatics, hydrides, halogens, and phosphorous-bearing species. Our derived abundances are compared to those for the latest observational data from large surveys and the Herschel telescope. Methods. A semi-analytical formalism based on parameterised fluid equations is used to describe the gas density, velocity, and temperature from 1 R * to 5 R *. The chemistry is described using a chemical kinetic network of reactions and a set of stiff, ordinary, coupled differential equations is solved. Results. The shocks induce an active non-equilibrium chemistry in the dust formation zone of IRC+10216 where the collision destruction of CO in the post-shock gas triggers the formation of O-bearing species such as H 2O and SiO. Most of the modelled molecular abundances agree very well with the latest values derived from Herschel data on IRC+10216. The hydrides form a family of abundant species that are expelled into the intermediate envelope. In particular, HF traps all the atomic fluorine in the dust formation zone. The halogens are also abundant and their chemistry is independent of the C/O ratio of the star. Therefore, HCl and other Cl-bearing species should also be present in the inner wind of O-rich AGB or supergiant stars. We identify a specific region ranging from 2.5 R * to 4 R *, where polycyclic aromatic hydrocarbons form and grow. The estimated carbon dust-to-gas mass ratio derived from the mass of aromatics formed ranges from 1.2 × 10 -3 to 5.8 × 10 -3 and agrees well with existing values deduced from observations. This aromatic formation region is situated outside hot layers where SiC 2 is produced as a bi-product of silicon carbide dust synthesis. The MgS grains can form from the gas phase but in lower quantities than those necessary to reproduce the strength of the 30 μm emission band. Finally, we predict that some molecular lines will show a flux variation with pulsation phase and time (e.g., H 2O), while other species will not (e.g., CO). These variations merely reflect the non-equilibrium chemistry that destroys and reforms molecules over a pulsation period in the shocked gas of the dust formation zone. © 2012 ESO.

Seddik R.,University of Basel
The Journal of biological chemistry | Year: 2012

GABA(B) receptors assemble from principle and auxiliary subunits. The principle subunits GABA(B1) and GABA(B2) form functional heteromeric GABA(B(1,2)) receptors that associate with homotetramers of auxiliary KCTD8, -12, -12b, or -16 (named after their K(+) channel tetramerization domain) subunits. These auxiliary subunits constitute receptor subtypes with distinct functional properties. KCTD12 and -12b generate desensitizing receptor responses while KCTD8 and -16 generate largely non-desensitizing receptor responses. The structural elements of the KCTDs underlying these differences in desensitization are unknown. KCTDs are modular proteins comprising a T1 tetramerization domain, which binds to GABA(B2), and a H1 homology domain. KCTD8 and -16 contain an additional C-terminal H2 homology domain that is not sequence-related to the H1 domains. No functions are known for the H1 and H2 domains. Here we addressed which domains and sequence motifs in KCTD proteins regulate desensitization of the receptor response. We found that the H1 domains in KCTD12 and -12b mediate desensitization through a particular sequence motif, T/NFLEQ, which is not present in the H1 domains of KCTD8 and -16. In addition, the H2 domains in KCTD8 and -16 inhibit desensitization when expressed C-terminal to the H1 domains but not when expressed as a separate protein in trans. Intriguingly, the inhibitory effect of the H2 domain is sequence-independent, suggesting that the H2 domain sterically hinders desensitization by the H1 domain. Evolutionary analysis supports that KCTD12 and -12b evolved desensitizing properties by liberating their H1 domains from antagonistic H2 domains and acquisition of the T/NFLEQ motif.

The susceptibility of agriculture to changing environmental conditions is arguably the most dangerous short-term consequence of climate change, and predictions on the geography of changes will be useful for implementing mitigation strategies. Ecological niche modeling (ENM) is a technique used to relate presence records of species to environmental variables. By extrapolation, ENM maps the suitability of a landscape for the species in question. Recently, ENM was successfully applied to predict the geographic distribution of agriculture. Using climate and soil conditions as predictor variables, agricultural suitability was mapped across the Old World. Here, I present analogous ENM-based maps of the suitability for agriculture under climate change scenarios for the year 2050. Deviations of predicted scenarios from a current conditions model were analyzed by (1) comparing relative average change across regions, and (2) by relating country-wide changes to the data indicative of the wealth of nations. The findings indicate that different regions vary considerably in whether they win or lose in agricultural suitability, even if average change across the entire study region is small. A positive relationship between the wealth of nations and change in agriculture conditions was found, but variability around this trend was high. Parts of Africa, Europe and southern and eastern Asia were predicted to be particularly negatively affected, while north-eastern Europe, among other regions, can expect more favorable conditions for agriculture. The results are presented as an independent "second opinion" to previously published, more complex forecasts on agricultural productivity and food supply variability due to climatic change, which were based on fitting environmental variables to yield statistics. © 2012 Springer Science+Business Media B.V.

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.

Meier C.,University of Basel
Swiss medical weekly | Year: 2011

Adequate intakes of calcium and vitamin D are essential preventive strategies and essential parts of any therapeutic regimen for osteoporosis. However, calcium supplementation is not without controversy and benefits on skeletal health need to be balanced against potential risks on cardiovascular disease. The published data so far suggest a potential detrimental effect of calcium supplement on cardiovascular health (i.e. myocardial infarction) although further prospective studies are needed to clarify the gradient of risk. Since food sources of calcium produce similar benefits on bone density as supplements and dietary calcium intake does not seem to be related with adverse cardiovascular effects, calcium intake from nutritional sources needs to be enforced. In patients with low calcium intake supplements are warranted aiming for a total calcium intake of 800 to 1000 mg/d together with adequate vitamin D replacement. Nevertheless we should keep in mind that for significant reduction in fracture risk, pharmacological treatment is mandatory in patients at risk of fractures irrespective of calcium and vitamin D supplementation.

Bednorz A.,University of Warsaw | Bruder C.,University of Basel | Reulet B.,Universite de Sherbrooke | Belzig W.,University of Konstanz
Physical Review Letters | Year: 2013

A long-standing problem in quantum mesoscopic physics is which operator order corresponds to noise expressions like âŸ̈I(-ω) I(ω)⟩, where I(ω) is the measured current at frequency ω. Symmetrized order describes a classical measurement while nonsymmetrized order corresponds to a quantum detector, e.g., one sensitive to either emission or absorption of photons. We show that both order schemes can be embedded in quantum weak-measurement theory taking into account measurements with memory, characterized by a memory function which is independent of a particular experimental detection scheme. We discuss the resulting quasiprobabilities for different detector temperatures and how their negativity can be tested on the level of second-order correlation functions already. Experimentally, this negativity can be related to the squeezing of the many-body state of the transported electrons in an ac-driven tunnel junction. © 2013 American Physical Society.

The target of rapamycin (TOR) is a conserved eukaryotic Ser/ Thr kinase that regulates cellular growth in response to the nutrient and energy state. TOR signaling plays an important role in the development of diseases such as cancer, obesity, and diabetes and in different redox-sensitive processes (hypoxia, apoptosis, and aging). Because TOR has been detected at different cellular membranes and in the nucleus, its localization may influence the specific signaling readout. To better understand how TOR can associate with different membranes, the lipid-binding properties of the redox-sensitive yeast TOR1 FATC domain (y1fatc) have been characterized by solution NMR spectroscopy. Binding studies with different lipids indicate that y1fatc interacts specifically with a membrane-mimetic environment but appears not to recognize a specific lipid headgroup. In both, the structures of oxidized and reduced micelle-bound y1fatc, residues Ile-2456 to Trp-2470 of the lipid-binding motif form a hydrophobic bulb that has a rim of charged residues. The diffusion constants for both micelle-bound states are consistent with the rotational correlation times from the analysis of the 15N relaxation data. Based on the Kd values, the oxidized form (Kd-0.31mM) binds dodecyl phosphocholine micelles slightly tighter than the reduced form (Kd - 1.86 mM). Binding studies with y1fatc in which one or both tryptophans (Trp-2466 and Trp-2470) were replaced by alanine suggest that these residues are important for the exact positioning in the membrane and that the other aromatic (His-2462, Tyr-2463, and Phe-2469) and aliphatic residues (Ile-2456, Leu-2459, Ile-2464, and Pro-2468) in the lipid-binding motif contribute significantly to the affinity. © 2010 by The American Society for Biochemistry and Molecular Biology, Inc.

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.

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.

Dwek E.,NASA | Cherchneff I.,University of Basel
Astrophysical Journal | Year: 2011

Two distinct scenarios for the origin of the ∼4 × 108 M⊙ of dust observed in the high-redshift (z = 6.4) quasar J1148+5251 have been proposed. The first assumes that this galaxy is much younger than the age of the universe at that epoch so that only supernovae (SNe) could have produced this dust. The second scenario assumes a significantly older galactic age, so that the dust could have formed in lower-mass asymptotic giant branch (AGB) stars. Presenting new integral solutions for the chemical evolution of metals and dust in galaxies, we offer a critical evaluation of these two scenarios and observational consequences that can discriminate between the two. We show that AGB stars can produce the inferred mass of dust in this object, however, the final mass of surviving dust depends on the galaxy's star formation history (SFH). In general, SNe cannot produce the observed amount of dust unless the average SN event creates over ∼2 M⊙ of dust in its ejecta. However, special SFHs can be constructed in which SNe can produce the inferred dust mass with a reasonable average dust yield of ∼0.15 M ⊙. The two scenarios propose different origins for the galaxy's spectral energy distribution, different star formation efficiencies and stellar masses, and consequently different comoving number densities of J1148+5251-type hyperluminous infrared (IR) objects. The detection of diagnostic mid-IR fine structure lines and more complete surveys determining the comoving number density of these objects can discriminate between the two scenarios.

Schaub N.,University of Basel
Swiss medical weekly | Year: 2011

The incidence of sepsis and the number of sepsis-related deaths are increasing, making sepsis the leading cause of death in critically ill patients in Europe and the U.S.A. Delayed recognition of sepsis and inappropriate initial antibiotic therapy are associated with an increase in mortality and morbidity. Rapid and accurate identification of sepsis and its causative organisms are a prerequisite for successful therapy. The current gold standard for the diagnosis of sepsis is culture of blood and other body fluids or tissues. However, even in severe sepsis, blood cultures (BC) yield the causative microorganism in only 20-40% of patients. Moreover, at least 24 hours are needed to get preliminary information about the potential organism. Therefore, novel laboratory methods for the diagnosis of sepsis, such as multiplex real-time polymerase chain reaction (PCR), matrix-assisted laser desorption ionisation (MALDI) time-of-flight (TOF) mass spectrometry (MS) (MALDI-TOF MS) and calorimetry, have been developed and evaluated.

Bolten M.I.,University of Basel
European Child and Adolescent Psychiatry | Year: 2013

Infant mental health problems include difficulties to regulate emotions or attention, crying, sleeping or feeding problems as well as aggressive behavior. Early identifications of these problems help to change developmental trajectories and improve developmental outcomes. Psychiatric assessment and classification have to take into account the rapid processes of development as well as the inseparable linkage between symptoms of the infant, psychosocial risks in the family environment, and parent-child relations. The proposed DSM-5 classification system presents a systematic description of mental health disorders which are relevant for infant psychiatry. However, the proposal has provided rather limited attention to developmental differences and parent- infant relations. Therefore, additional classification systems, like the Zero-to-Three (DC: 0-3R), are strongly recommended. In terms of assessment and in accordance with the guidelines of the American Academy of Child and Adolescent Psychiatry, infant psychiatrists have to consider the close relation between somatic and mental health and the interplay between behaviors of the caregiver and the infant. Therefore, the assessment has to be multidisciplinary and relationship based. A standard assessment in infancy includes a clinical interview, behavior observations, caregiver questionnaires, and a pediatric screening. All assessments should pay attention to motor, cognitive, language, and social-emotional development. Because infant development is embedded in the family context, socio-economic factors, parents' mental problems, including drug abuse, domestic violence, and trauma history should be assessed. The treatment has to be oriented toward symptoms and development and has to address underlying medical conditions. The focus should be on parent-child interactions. Evidence-based interventions are based on attachment theory, use social-learning perspectives, and behavioral approaches. © Springer-Verlag Berlin Heidelberg 2012.

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.

Bieri O.,University of Basel
Magnetic Resonance in Medicine | Year: 2011

Conceptually, the only flaw in the standard steady-state free precession theory is the assumption of quasi-instantaneous radio-frequency pulses, and 10-20% signal deviations from theory are observed for common balanced steady-state free precession protocols. This discrepancy in the steady-state signal can be resolved by a simple T2 substitution taking into account reduced transverse relaxation effects during finite radio-frequency excitation. However, finite radio-frequency effects may also affect the transient phase of balanced steady-state free precession, its contrast or its spin-echo nature and thereby have an adverse effect on common steady-state free precession magnetization preparation methods. As a result, an in-depth understanding of finite radio-frequency effects is not only of fundamental theoretical interest but also has direct practical implications. In this article, an analytical solution for balanced steady-state free precession with finite radio-frequency pulses is derived for the transient phase (under ideal conditions) and in the steady state demonstrating that balanced steady-state free precession key features are preserved but revealing an unexpected dependency of finite radio-frequency effects on relaxation times for the transient decay. Finally, the mathematical framework reveals that finite radio-frequency theory can be understood as a generalization of alternating repetition time and fluctuating equilibrium steady-state free precession sequence schemes. © 2010 Wiley-Liss, Inc.

Bitzer J.,University of Basel | Simon J.A.,George Washington University
Contraception | Year: 2011

Development of hormonal contraception marked a revolutionary step in social change that has improved the lives of women and families worldwide. Since the first oral contraceptive was introduced in the 1960s, hormonal contraception has undergone various stages of advancement. Today, oral contraceptive regimens are safer and more tolerable, with equal or improved efficacy, than the early formulations. Incremental decreases in the dose of estrogens have helped to alleviate some of the unwanted estrogenic side effects of combined hormonal contraceptives. Progestogens have also evolved over time, and newer generations of progestins have minimal side effects. New delivery methods have further extended the range of options available to women. Among these, the transdermal patch and vaginal ring are widely used. This review examines available combined hormonal contraceptive options and compares them, where data are available, for efficacy, safety, cycle control, adverse events profiles and associated risks, and user preference and satisfaction. We also examine particular areas of interest, including bone mineral density, venous thrombosis and use of antiepileptic drugs. © 2011 Elsevier Inc.

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.

Leuppi J.D.,University of Basel
Respiration; international review of thoracic diseases | Year: 2010

BACKGROUND: Diagnosis of chronic obstructive pulmonary disease (COPD) and its severity determination is based on spirometry. The quality of spirometry is crucial. OBJECTIVES: Our aim was to assess the quality of spirometry performed using a spirometer with automated feedback and quality control in a general practice setting in Switzerland and to determine the prevalence of airflow limitation in smokers aged > or =40 years. METHOD: Current smokers > or =40 years of age were consecutively recruited for spirometry testing by general practitioners. General practitioners received spirometry training and were provided with an EasyOne spirometer. Spirometry tests were assigned a quality grade from A to D and F, based on the criteria of the National Lung Health Education Program. Only spirometry tests graded A-C (reproducible measurements) were included in the analysis of airflow limitation. RESULTS: A total of 29,817 spirometries were analyzed. Quality grades A-D and F were assigned to 33.9, 7.1, 19.4, 27.8 and 11.8% of spirometries, respectively. 95% required < or =5 trials to achieve spirometries assigned grade A. The prevalence of mild, moderate, severe and very severe airway obstruction in individuals with spirometries graded A-C was 6, 15, 5 and 1%, respectively. CONCLUSION: Spirometries in general practice are of acceptable quality with reproducible spirometry in 60% of measurements. Airway obstruction was found in 27% of current smokers aged > or =40 years. Office spirometry provides a simple and quick means of detecting airflow limitation, allowing earlier diagnosis and intervention in many patients with early COPD. Copyright 2009 S. Karger AG, Basel.

Basler M.,University of Basel
Philosophical Transactions of the Royal Society B: Biological Sciences | Year: 2015

The type VI secretion systems (T6SS) are present in about a quarter of all Gramnegative bacteria. Several key components of T6SS are evolutionarily related to components of contractile nanomachines such as phages and R-type pyocins. The T6SS assembly is initiated by formation of a membrane complex that binds a phage-like baseplate with a sharp spike, and this is followed by polymerization of a long rigid inner tube and an outer contractile sheath. Effectors are preloaded onto the spike or into the tube during the assembly by various mechanisms. Contraction of the sheath releases an unprecedented amount of energy, which is used to thrust the spike and tube with the associated effectors out of the effector cell and across membranes of both bacterial and eukaryotic target cells. Subunits of the contracted sheath are recycled by T6SS-specific unfoldase to allow for a new round of assembly. Live-cell imaging has shown that the assembly is highly dynamic and its subcellular localization is in certain bacteria regulated with a remarkable precision. Through the action of effectors, T6SS has mainly been shown to contribute to pathogenicity and competition between bacteria. This review summarizes the knowledge that has contributed to our current understanding of T6SS mode of action. © 2015 The Authors.

Broz P.,University of Basel
Cell Research | Year: 2015

Inflammasomes control host cell death and inflammation in response to sterile or infectious stimuli. Two recent reports published in Science reveal the structural basis for the assembly of NAIP-NLRC4 inflammasomes. © 2015 IBCB, SIBS, CAS.

Erol R.Y.,University of Basel | Orth U.,University of Bern
Developmental psychology | Year: 2014

We examined the effects of self-esteem development on the development of relationship satisfaction in 2 samples of couples. Study 1 used data from both partners of 885 couples assessed 5 times over 12 years, and Study 2 used data from both partners of 6,116 couples assessed 3 times over 15 years. The pattern of results was similar across the 2 studies. First, development of relationship satisfaction could be modeled as a couple-level process. Second, initial level of self-esteem of each partner predicted the initial level of the partners' common relationship satisfaction, and change in self-esteem of each partner predicted change in the partners' common relationship satisfaction. Third, these effects did not differ by gender and held when controlling for participants' age, length of relationship, health, and employment status. Fourth, self-esteem similarity among partners did not influence the development of their relationship satisfaction. The findings suggest that the development of self-esteem in both partners of a couple contributes in a meaningful way to the development of the partners' common satisfaction with their relationship.

Munch M.,Ecole Polytechnique Federale de Lausanne | Bromundt V.,University of Basel
Dialogues in Clinical Neuroscience | Year: 2012

Environmental light synchronizes the primary mammalian biological clock in the suprachiasmatic nuclei, as well as many peripheral clocks in tissues and cells, to the solar 24-hour day. Light is the strongest synchronizing agent (zeitgeber) for the circadian system, and therefore keeps most biological and psychological rhythms internally synchronized, which is important for optimum function. Circadian sleep-wake disruptions and chronic circadian misalignment, as often observed in psychiatric and neurodegenerative illness, can be treated with light therapy. The beneficial effect on circadian synchronization, sleep quality, mood, and cognitive performance depends on timing, intensity, and spectral composition of light exposure. Tailoring and optimizing indoor lighting conditions may be an approach to improve wellbeing, alertness, and cognitive performance and, in the long term, producing health benefits. © 2012 LLS SAS.

Rosenthal R.,University of Basel | Dwan K.,University of Liverpool
Annals of Surgery | Year: 2013

Objective: To evaluate discrepancies between trial registry entries and final reports of randomized controlled trials (RCTs) published in major general surgical journals. Background: Health care decisions are based on published results in peerreviewed journals. Mandatory trial registration was introduced to increase transparency and reduce publication and outcome reporting bias. Methods: The discrepancy rate between trial registry entries and final reports of all RCTs published during 2010 in the Annals of Surgery, Archives of Surgery, and British Journal of Surgery was evaluated. Results: Of 596 identified studies, 545 were excluded because they were not RCTs or interim reports/secondary analysis of RCTs or because of missing trial registry information. In the remaining 51 RCTs, prospective registration was found in 9.8% (n = 5), registration during trial conduct in 33.3% (n = 17), and retrospective registration in 56.9% (n = 29), respectively. For the primary and secondary outcomes, there was no discrepancy in 54.9% and 33.3%, complete omission in 7.8% and 31.3%, new introduction in 7.8% and 39.2%, a change in definition in 9.8% and 5.8%, downgrading from primary to secondary in 21.6%, and upgrading from secondary to primary in 13.7%. There were few discrepancies in randomization, blinding, and intervention and some in targeted sample size and inclusion/exclusion criteria. Conclusions: When interpreting the results of surgical RCTs, the possibility of selective reporting, and thus outcome reporting bias, has to be kept in mind. For future trials, prospective registration should be strictly respected with the ultimate goal to increase transparency and contribute to high-level evidence reports for optimal patient care in surgery. Copyright © 2013 by Lippincott Williams and Wilkins.

Trees are taller than shrubs, grasses, and herbs. What is the disadvantage of being tall so that trees are restricted to warmer regions than low stature life forms? This article offers a brief review of the current state of biological treeline theory, and then explores the significance of tallness from a carbon balance, freezing resistance, and microclimatological perspective. It will be argued that having of a woody stem is neither a burden to the carbon balance nor does it add to the risk of freezing damage. The physiological means of trees to thrive in cold climates are similar to small stature plants, but due to their size, and, thus, closer aerodynamic coupling to air circulation, trees experience critically low temperatures at lower elevation and latitude than smaller plants. Hence, trees reach a limit at treeline for physical reasons related to their stature. Copyright © Royal Swedish Academy of Sciences 2012.

Meyer U.A.,University of Basel
Clinical Pharmacology and Therapeutics | Year: 2012

Personalized medicine is a strategy to prevent, diagnose, and treat disease so as to achieve an optimal result for the individual. The sequencing of the human genome and other technological advances have revealed the extent of genetic diversity and the relative contribution of genetic and nongenetic factors to human health, disease, and drug response. The challenge is to translate this knowledge into tangible benefits for the patient. © 2012 american Society for clinical Pharmacology and Therapeutics.

The anatomy of human teeth reflects its usage. Spatially resolved X-ray scattering permits quantitative studies of the characteristic arrangement of the anisotropic calcium phosphate crystallites and the collagen fibers within the hard tissues of the crown. The present study summarizes the distinctive nanometer-sized anatomical features of the tooth hard tissues including their interface taking advantage of spatially resolved synchrotron radiation-based small-angle X-ray scattering. The comparison of slices from eight teeth indicates a long-range organization of tooth nanostructures.

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.

Wetzel A.,University of Basel
Palaeogeography, Palaeoclimatology, Palaeoecology | Year: 2013

In the biologically high-productive area off Vietnam authigenic carbonates formed in the bioturbated zone while methane was oxidized microbially under anaerobic conditions. Open crustacean burrows (Spongeliomorpha) connected to the seafloor acted as conduits for methane as suggested by intense cementation of burrow walls having a light C-isotope signature. Although seawater circulated within these open, inhabited tubes, conditions favorable for anaerobic oxidation of methane (AOM) occurred <1mm away from the tubes. Trace fossils document a gradual stiffening and induration of the material finally reaching hardground condition (indicated by Trypanites). Cementation started at several spots that coalesced later to form the nodule. Carbon isotopes indicate a biogenic methane source (δ13Ccarb reaching -49 to -40‰ V-PDB), while higher δ13C values imply mixing with carbon from other sources that is very likely within the bioturbated zone. The cement is generally fine grained (<5μm); calcite forms about 3/4 of the cement, dolomite about 1/4, and aragonite a minor proportion. High δ18O values of +5±1‰ reflect the general 18O-enriched isotope signature of the bottom water in South China Sea especially during glacial times, but influence of water released from decaying gas hydrate cannot be excluded. The studied nodule was found on top of a slump that displaced it. © 2013 Elsevier B.V.

Tilting marks, defined here as linear tool marks having transverse ornamentation, are produced in shallow water when the oscillatory action of waves of short wavelength tilt grounded objects rhythmically in such a way that they move and push sediment aside. These tool marks can resemble trace fossils, particularly if they are bilaterally symmetrical. Even asymmetrical objects can produce symmetrical tilting marks because the shape of the mark only depends on the geometry of the ground-touching part of the object, which may be partially floating. Objects of either soft or hard consistency, such as jellyfish or wood, respectively, can produce tilting marks. Tilting marks are normally produced linearly parallel or at an angle to the direction of wave propagation and do not show sharp bends or curves. Tilting marks can be formed on plane beds as well as rippled surfaces. Tilting marks can be distinguished from trace fossils by taking into account the geometry (symmetry), the direction of movement, and the mainly linear course and the internal pattern. © 2013 Elsevier B.V.

Hugle T.,University of Basel
Swiss medical weekly | Year: 2014

Mast cells are tissue-bound cells of the innate immune system which are well known for immunoglobuline (Ig)E-triggered degranulation in allergic reactions. More recently, an important role of mast cells has been described in chronic inflammatory and autoimmune disorders which are often associated with fibrosis or sclerosis. Innate immune receptors such as Fc-, toll-like- or NOD-like receptors stimuli can trigger mast cell degranulation and enhance immunological danger signals. Whereas fulminant degranulation of mast cell vesicles is observed in anaphylaxis, piecemeal degranulation or transgranulation are mechanisms for a slower release of their granula. A cocktail of cytokines, growth factors and proteoglycans is produced and stored in granula of mast cells. Mast cells are a substantial reservoir of both preformed inflammatory factors (i.e., TNF-alpha and IL-17) and factors that can trigger a profibrotic, Th-2-polarised inflammation (i.e., IL-4 and IL-10). In systemic sclerosis, mast cell vesicles are the main source of transforming growth factor (TGF)-beta. Cell-to-cell contact between mast cells and fibroblasts occurs in the affected tissue, supporting the hypothesis that transgranulation might be an important mechanism in fibrosis. The direct release of proteoglycans such as hyaluronic acid into the interstitial space is a further stimulus for matrix remodelling. Mast cell hyperactivity has also been demonstrated in primary fibrotic disorders such as lung, cardiac or renal fibrosis. The exact trigger for mast cell degranulation however is not known. Notwithstanding, at a very early time point of fibrosis, mast cell inhibition by stabilisers or blockage of the tyrosine kinase receptor c-kit by masitinib could be a therapeutic option.

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.

Zeth K.,University of Basel
Biochemical Society Transactions | Year: 2012

Bacteriocins are narrow-spectrum protein antibiotics released to kill related bacteria of the same niche. Uptake of bacteriocins depends critically on the presence of an uptake receptor in the outer membrane, a translocation pore and an energy-dependent activating system of the inner membrane. Most bacteriocins act on the inner membrane as pore-forming toxins or they target cytoplasmic DNA/RNA and ribosomal synthesis respectively. Only two bacteriocins are known to become activated in the periplasmic space and to inhibit the renewal process of the peptidoglycan structure. In Escherichia coli, the Cma (colicin M) phosphatase is activated in the periplasmic space by the FkpA chaperone and subsequently degrades the C55-PP precursor unit of the peptidoglycan. Pst (pesticin) from Yersinia pestis carries a lysozyme homology domain to degrade peptidoglycan. Import of Pst is only achieved if the N-terminal translocation domain can span the outer membrane and if extensive unfolding of the protein during membrane passage is permitted. There is considerable plasticity in the import pathway since a chimaera comprising the activity domain replaced by T4 lysozyme is also translocated and active in killing those bacteria carrying the FyuA receptor. ©The Authors Journal compilation ©Biochemical Society.

Using variothermal polymer micro-injection molding, disposable arrays of eight polymer micro-cantilevers each 500 μm long, 100 μm wide and 25 μm thick were fabricated. The present study took advantage of an easy flow grade polypropylene. After gold coating for optical read-out and asymmetrical sensitization, the arrays were introduced into the Cantisens(®) Research system to perform mechanical and functional testing. We demonstrate that polypropylene cantilevers can be used as biosensors for medical purposes in the same manner as the established silicon ones to detect single-stranded DNA sequences and metal ions in real-time. A differential signal of 7 nm was detected for the hybridization of 1 μM complementary DNA sequences. For 100 nM copper ions the differential signal was found to be (36 ± 5) nm. Nano-mechanical sensing of medically relevant, nanometer-size species is essential for fast and efficient diagnosis.

Jeney S.,University of Basel
Nanotechnology | Year: 2010

We introduce a method for the acquisition of single molecule force measurements of ligand-receptor interactions using the photonic force microscope (PFM). Biotin-functionalized beads, manipulated with an optical trap, and a streptavidin-functionalized coverslip were used to measure the effect of different pulling forces on the lifetime of individual streptavidin-biotin complexes. By optimizing the design of the optical trap and selection of the appropriate bead size, pulling forces in excess of 50 pN were achieved. Based on the amplitude of three-dimensional (3D) thermal position fluctuations of the attached bead, we were able to select for a bead-coverslip interaction that was mediated by a single streptavidin-biotin complex. Moreover, the developed experimental system was greatly accelerated by automation of data acquisition and analysis. In force-dependent kinetic measurements carried out between streptavidin and biotin, we observed that the streptavidin-biotin complex exhibited properties of a catch bond, with the lifetime increasing tenfold when the pulling force increased from 10 to 20 pN. We also show that silica beads were more appropriate than polystyrene beads for the force measurements, as tethers, longer than 200 nm, could be extracted from polystyrene beads.

Scientists are caught in a prisoners' dilemma of authorship ethics and the misuse of impact factors, which damages the whole scientific endeavor. Breaking out of this trap requires the dedicated engagement of the whole community. © 2014 The Author.

Nigg S.E.,University of Basel
Physical Review A - Atomic, Molecular, and Optical Physics | Year: 2014

We propose the implementation of a deterministic Hadamard gate for logical photonic qubits encoded in superpositions of coherent states of a harmonic oscillator. The proposed scheme builds on a recently introduced set of conditional operations in the strong dispersive regime of circuit QED [Z. Leghtas, Phys. Rev. A 87, 042315 (2013)PLRAAN1050-294710.1103/PhysRevA.87. 042315]. We further propose an architecture for coupling two such logical qubits and provide a universal set of deterministic quantum gates. Based on parameter values taken from the current state of the art, we give estimates for the achievable gate fidelities accounting for fundamental gate imperfections and finite coherence time due to photon loss. © 2014 American Physical Society.

Broz P.,University of Basel
Cell Research | Year: 2016

The non-canonical inflammasome triggers host cell death and inflammation upon recognition of cytosolic LPS. A recent report in Cell now shows that Outer Membrane Vesicles (OMVs) of extracellular Gram-negative bacteria can deliver LPS into the host cell cytosol. © 2016 Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences

Constable E.C.,University of Basel
Chemical Society Reviews | Year: 2013

Chirality is a concept that lies at the heart of organic chemistry but is often ignored in discussions of inorganic systems. This omission is all the more surprising, given the seminal role played by the study of chiral systems in the development of coordination chemistry. This tutorial review gives a brief introduction to the concept of chirality in coordination and supramolecular compounds for the non-specialist. © 2013 The Royal Society of Chemistry.

The development of chemical sensors is a subject that continues to fascinate chemists in academic research. Aside from the purely academic interest, there is of course the important issue of finding suitable sensors for harmful chemical substances that might be present in the environment or at the workplaces. In addition, there is the phenomenon of luminescence vapochromism, often called vapoluminescence, which refers to changes in photoluminescence properties in the course of vapor exposure. The class of compounds in which these two closely related phenomena occur most frequently is undoubtedly the area of organometallic and coordination complexes. This review therefore focuses on transition-metal compounds that change color and/or their emission properties when exposed to VOCs. Hydrogen bond donation from methanol to the aminophosphine ligands may render the overall complex less flexible, making multiphonon relaxation less efficient.

This is a contribution to the history of scientific advance in the past 70 years concerning the identification of genetic information, its molecular structure, the identification of its functions and the molecular mechanisms of its evolution. Particular attention is thereby given to horizontal gene transfer among microorganisms, as well as to biosafety considerations with regard to beneficial applications of acquired scientific knowledge. © 2014 by the author; licensee MDPI, Basel, Switzerland.

Spagnolo P.,Medical University Clinic | Spagnolo P.,University of Basel | Maher T.M.,National Health Research Institute | Maher T.M.,Imperial College London | Richeldi L.,University of Southampton
Pharmacology and Therapeutics | Year: 2015

Idiopathic pulmonary fibrosis (IPF) is the most common and lethal of the idiopathic interstitial pneumonias with an estimated 5-year survival of approximately 20%. In the last two decades our understanding of disease pathogenesis has substantially evolved and novel compounds have been developed consequent to the increasing knowledge of the mechanisms underlying disease pathobiology. The disease appears to be driven - following chronic injury - by abnormal/dysfunctional alveolar epithelial cells that promote fibroblast recruitment and proliferation, resulting in scarring of the lung and irreversible loss of function. With very few exceptions, clinical trials evaluating novel potential therapies have provided disappointing results. More recently, pirfenidone and nintedanib, two compounds with pleiotropic mechanisms of action, have proven effective in slowing functional decline and disease progression in IPF patients with mild to moderate functional impairment, highlighting the importance of timely diagnosis and administration of treatment in early stages of disease. However, due to the complexity and uncertainties intrinsic to IPF, it is essential that each therapeutic strategy be tailored to the individual patient, after evaluation of potential benefits and risks. This article provides an overview of the most recent clinical trials in IPF and discusses how their results are going to change the clinical and clinical research landscape in IPF. A number of agents with high potential are currently being tested and many more are ready for clinical trials. Their completion is critical for achieving the ultimate goal of curing patients with IPF. © 2015 Elsevier Ltd. All rights reserved.

Nyffeler M.,University of Basel | Pusey B.J.,University of Western Australia
PLoS ONE | Year: 2014

More than 80 incidences of fish predation by semi-aquatic spiders - observed at the fringes of shallow freshwater streams, rivers, lakes, ponds, swamps, and fens - are reviewed. We provide evidence that fish predation by semi-aquatic spiders is geographically widespread, occurring on all continents except Antarctica. Fish predation by spiders appears to be more common in warmer areas between 40° S and 40° N. The fish captured by spiders, usually ranging from 2-6 cm in length, are among the most common fish taxa occurring in their respective geographic area (e.g., mosquitofish [Gambusia spp.] in the southeastern USA, fish of the order Characiformes in the Neotropics, killifish [ Aphyosemion spp.] in Central and West Africa, as well as Australian native fish of the genera Galaxias, Melanotaenia, and Pseudomugil). Naturally occurring fish predation has been witnessed in more than a dozen spider species from the superfamily Lycosoidea (families Pisauridae, Trechaleidae, and Lycosidae), in two species of the superfamily Ctenoidea (family Ctenidae), and in one species of the superfamily Corinnoidea (family Liocranidae). The majority of reports on fish predation by spiders referred to pisaurid spiders of the genera Dolomedes and Nilus (>75% of observed incidences). There is laboratory evidence that spiders from several more families (e.g., the water spider Argyroneta aquatica [Cybaeidae], the intertidal spider Desis marina [Desidae], and the 'swimming' huntsman spider Heteropoda natans [Sparassidae]) predate fish as well. Our finding of such a large diversity of spider families being engaged in fish predation is novel. Semi-aquatic spiders captured fish whose body length exceeded the spiders' body length (the captured fish being, on average, 2.2 times as long as the spiders). Evidence suggests that fish prey might be an occasional prey item of substantial nutritional importance. © 2014 Nyffeler, Pusey.

Riecher-Rossler A.,University of Basel
European Psychiatry | Year: 2010

Many mental disorders show marked gender differences as regards prevalence, symptomatology, risk factors or course. Other disorders do per definition only occur in women - e.g. premenstrual dysphoric disorder (PMDD) - or are markedly influenced by female specific factors such as hormonal changes over the life cycle or during reproductive processes. Current classification systems have tried to take into account these gender aspects, but some problems will certainly have to be discussed again with the next revisions of the ICD and DSM. As regards gender differences in prevalence and symptomatology questions of gender bias in diagnostic instruments and diagnostic criteria will have to be readdressed. New findings from unselected epidemiological samples, which were analysed by gender, will have to be taken into account as well as new findings from research into gender specific personality traits, which can influence the symptomatology of mental disorders. Decisions will have to be taken whether to revise existing diagnostic criteria and provide alternative diagnostic thresholds for men and women or even to develop alternative criteria sets in certain disorders, or rather to enhance the gender neutrality of criteria. A further question to be addressed will be that of gender specific diagnoses versus diagnostic specifiers. In the whole discussion two main aims of classification should be given priority: the research aim of identifying genuine entities with a common aetiology, which means we should be able to identify specific diagnostic entities with descriptive, construct, and predictive validity quite independently of the influences of gender; and the clinical aim to improve treatment and care for men and women, which often means to offer gender-specific approaches. © 2009 Elsevier Masson SAS.

Mack I.,University of Basel
Pediatric Infectious Disease Journal | Year: 2016

BACKGROUND.: Risk factors promoting rhinovirus (RV) infections are inadequately described in healthy populations, especially infants. OBJECTIVES.: To determine the frequency of symptomatic and asymptomatic RV infections and identify possible risk factors from host and environment among otherwise healthy infants. METHODS.: In a prospective birth cohort, respiratory health was assessed in 41 term-born infants by weekly telephone interviews during the first year of life, and weekly nasal swabs were collected to determine RV prevalence. In a multilevel logistic regression model, associations between prevalence and respiratory symptoms during RV infections and host/environmental factors were determined. RESULTS.: 27% of nasal swabs in 41 infants tested positive for RVs. Risk factors for RV prevalence were autumn months (OR=1.71, p=0.01, 95% CI 1.13-2.61), outdoor temperatures between 5-10 °C (OR=2.33, p=0.001, 95% CI 1.41-3.86), older siblings (OR=2.60, p=0.001, 95% CI 1.50-4.51) and childcare attendance (OR=1.53, p=0.07, 95% CI 0.96-2.44). 51% of RV-positive samples were asymptomatic. Respiratory symptoms during RV infections were less likely during the first three months of life (OR=0.34, p=0.003, 95% CI 0.17-0.69) and in infants with atopic mothers (OR=0.44, p=0.008, 95% CI 0.24-0.80). Increased tidal volume (OR=1.67, p=0.03, 95% CI 1.04-2.68) and outdoor temperatures between 2-5 °C (OR=2.79, p=0.02, 95% CI 1.17-6.61) were associated with more symptoms. CONCLUSIONS.: RVs are highly prevalent during the first year of life, and most infections are asymptomatic. Frequency of RV infections is associated with environmental factors, while respiratory symptoms during RV infections are linked to host determinants like infant age, maternal atopy, or premorbid lung function. Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.

Fritz R.D.,University of Basel | Radziwill G.,Albert Ludwigs University of Freiburg
Biochimica et Biophysica Acta - Molecular Cell Research | Year: 2011

FoxO transcription factors mediate anti-proliferative and pro-apoptotic signals and act as tumor suppressors in cancer. Posttranslational modifications including phosphorylation and acetylation regulate FoxO activity by a cytoplasmicxnuclear shuttle mechanism. Scaffold proteins coordinating signaling pathways in time and space play a critical role in this process. CNK1 acts as a scaffold protein in several signaling pathways controlling the function of FoxO proteins. An understanding of CNK1 and other scaffolds in the FoxO signaling network will provide insights how to release the tumor suppressor function of FoxO as a possibility to block oncogenic pathways. This article is part of a Special Issue entitled: P13K-AKT-FoxO axis in cancer and aging. © 2011 Elsevier B.V.

Protestantism is not a centralized religion. It is composed by many independent Churches having different moral and ethical standards. This review concentrates on the ethical principles prevalent in most modern European Reformed Churches. It does not intend to discuss the ethical principles of many other Protestant Churches present mainly in the USA. The common foundations of Protestant theology are the "five sola ("Sola scriptura", Sola fide", "Sola gratia", Solus Christus or Solo Christo", "Soli deo gloria"). In opposition to the Catholic Church, no intermediary is needed between the Bible and the believer. As a consequence, Protestant Churches have no Magisterium, such as the Catholic Church. Therefore Protestant Churches cannot declare a certain position to be the "official position". Each Christian is personally responsible for all his acts, including his ethical behaviour. There is no complete unanimity among all Protestants on ethics or on any other issue. Human dignity, personal rights and self-determination have to be respected in each ethical consideration. The supersession of the Old Mosaic Covenant (including traditional Jewish law or Halakhah, maintained in Catholicism) by the New Covenant and by Christian Theology has an important impact on Protestant ethics in reproductive medicine. In the New Covenant, the Protestants Churches did not maintain the mandatory obligation from the old Mosaic Covenant to be fruitful and to multiply: there is no divine obligation by God to procreate. As a consequence, contraception is not a sin and not unethical. The status of the embryo is the key for the ethical consideration of all methods used in reproductive medicine. Most representatives of modern Protestant theology and bioethics defend the opinion that the embryo is not an independent human being as is the newborn child. For most Protestant bio-ethicists, as long as an embryo has no nervous system, no organs and no pain receptors, it cannot be seen as a human being sensu strictiori: the zygote is not yet a "human being". The ethical right to be protected prenatally increases gradually with the age and the development of the embryo. Following this so-called gradualist interpretation, the early stages of an embryo merit ethically a special status: although they have already "human life", they are not yet a "human being". All ethical considerations in modern reproductive medicine discussed in this review are based on this concept of the status of the embryo. It depends largely on the acceptance or rejection of this special status of the embryo, if a Protestant considers a certain method in reproductive medicine to be ethical or unethical. © 2013 Informa UK Ltd. All rights reserved: reproduction in whole or part not permitted.

Bitzer J.,University of Basel
Best Practice and Research: Clinical Endocrinology and Metabolism | Year: 2013

Taking into account the biological and psychosocial changes during the transition from childhood to adulthood adolescents would need a contraceptive method which ideally would be very effective, independent of compliance, without major health risks during use and no negative impact on the future health of the adolescent, protective against STI, favorable for bone development, with no or only few side effects and having some preventive and therapeutic potential with respect to frequent health problems of adolescent girls. Combined oral contraceptives (COC) used regularly and consistently have a more than 99% efficacy to prevent a pregnancy. COCs have a very low health risk (almost exclusively thromboembolic disease) which seems to differ marginally with respect to dosage and type of the components. Progestogen only oral contraceptives do not have any major negative health impact. The leading side effect is irregular bleeding which in COC users is mainly during the first 3 months and in progestogen only users during the period of use. Other side effects are reported but their frequency is similar to placebo. COC protect against endometrial and ovarian cancer and they may have beneficial effects on a variety of menstrual complaints and acne, which are frequent problems during adolescence. To be effective COCs have to be taken regularly which is frequently not the case. This diminishes considerably their effectiveness depending on the individual compliance. They do not protect against STI and may even have an inhibitory effect on the use of condoms. For most adolescents the risk benefit profile of oral contraceptives is favorable and makes this method valuable. At the same time the prescription of oral contraceptives for adolescents need to be individualized by taking into account the individual risk/benefit profile. Specialized counseling with a high degree of confidentiality adapted to the knowledge and needs of the individual adolescent is desirable. © 2012 Elsevier Ltd. All rights reserved.

Rice tungro disease is caused by synergistic interaction of an RNA picorna-like virus Rice tungro spherical virus (RTSV) and a DNA pararetrovirus Rice tungro bacilliform virus (RTBV). It is spread by insects owing to an RTSV-encoded transmission factor. RTBV has evolved a ribosome shunt mechanism to initiate translation of its pregenomic RNA having a long and highly structured leader. We found that a long leader of RTSV genomic RNA remarkably resembles the RTBV leader: both contain several short ORFs (sORFs) and potentially fold into a large stem-loop structure with the first sORF terminating in front of the stem basal helix. Using translation assays in rice protoplasts and wheat germ extracts, we show that, like in RTBV, both initiation and proper termination of the first sORF translation in front of the stem are required for shunt-mediated translation of a reporter ORF placed downstream of the RTSV leader. The base pairing that forms the basal helix is required for shunting, but its sequence can be varied. Shunt efficiency in RTSV is lower than in RTBV. But in addition to shunting the RTSV leader sequence allows relatively efficient linear ribosome migration, which also contributes to translation initiation downstream of the leader. We conclude that RTSV and RTBV have developed a similar, sORF-dependent shunt mechanism possibly to adapt to the host translation system and/or coordinate their life cycles. Given that sORF-dependent shunting also operates in a pararetrovirus Cauliflower mosaic virus and likely in other pararetroviruses that possess a conserved shunt configuration in their leaders it is tempting to propose that RTSV may have acquired shunt cis-elements from RTBV during their co-existence.

O'Reilly E.,University of Manchester | Kohler V.,University of Basel | Flitsch S.L.,University of Manchester | Turner N.J.,University of Manchester
Chemical Communications | Year: 2011

Cytochrome P450 monooxygenases (P450s or CYPs) are a unique family of enzymes which are capable of catalysing the regio- and stereospecific oxidation of non-functionalised hydrocarbons. Despite the enormous synthetic potential of P450s, these enzymes have yet to be extensively employed for research purposes or in industry. Lack of stability, low activity, narrow substrate specificity, expensive cofactor requirements, limited solvent tolerance and electron supply are some of the main reasons why the academic and industrial implementation of these important biocatalysts remains a challenge. Considering the significance of P450s, many research groups have focused on improving their properties in an effort to make more robust catalysts with broad synthetic applications. This article focuses on some of the factors that have limited the exploitation of P450s and explores some of the significant steps that have been taken towards addressing these limitations. © 2011 The Royal Society of Chemistry.

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.

This article presents epidemiological and clinical findings from the Basel research centre parti-cipating in the WHO/EURO Multicentre Study on Suicidal Behaviour. Between January 2003 and December 2006, 984 suicide attempts were documented for patients presenting at medical institutions with a suicide attempt. The mean suicide attempt rate was 164/100,000 inhabitants. Women attempted suicide nearly twice as often as men. The highest suicide attempt rates were found for women aged 20-24 years, for men aged 30-34 years, and for people who were unmarried, of foreign nationality, and of low education or low employment status. 'Soft methods' were used significantly more often than 'hard methods'. Of the suicide attempt methods employed, a relatively high proportion was accounted for by self-poisoning with drugs (X60-64), especially with non-steroidal anti-inflammatory drugs, benzodiazepines and antidepressants. Significant gender differences were found in the various methods and in the frequency of psychiatric diagnoses. A total of 98.7% of the attempters were diagnosed with a psychiatric disorder according to ICD-10; 35% suffered from an affective disorder. Men were significantly more frequently affected by substance abuse disorder or psychosis, whereas in women adjustment disorders and personality disorders were diagnosed significantly more often. This study offers the first published representative data of an entire Swiss county. Established sociodemographic and clinical risk factors for suicide attempts were reproduced. The identification of risk factors contributes to developing local targeted prevention strategies, for example education of risk groups and caregivers, and pharmacolegal consequences for package sizes. Gender- and age-specific prevention and aftercare programmes are indicated.

Functional magnetic resonance imaging (fMRI) is an important and novel neuroimaging modality for patients with brain tumors. By non-invasive measurement, localization and lateralization of brain activiation, most importantly of motor and speech function, fMRI facilitates the selection of the most appropriate and sparing treatment and function-preserving surgery. Prerequisites for the diagnostic use of fMRI are the application of dedicated clinical imaging protocols and standardization of the respective imaging procedures. The combination with diffusion tensor imaging (DTI) also enables tracking and visualization of important fiber bundles such as the pyramidal tract and the arcuate fascicle. These multimodal MR data can be implemented in computer systems for functional neuronavigation or radiation treatment. The practicability, accuracy and reliability of presurgical fMRI have been validated by large numbers of published data. However, fMRI cannot be considered as a fully established modality of diagnostic neuroimaging due to the lack of guidelines of the responsible medical associations as well as the lack of medical certification of important hardware and software components. This article reviews the current research in the field and provides practical information relevant for presurgical fMRI.

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.

Evidence suggests a confounding effect of mismatch repair (MMR) status on immune response in colorectal cancer. The identification of innate and adaptive immune cells, that can complement the established prognostic effect of CD8 in MMR-proficient colorectal cancers patients, representing 85% of all cases, has not been performed. Colorectal cancers from a test (n=1197) and external validation (n=209) cohort of MMR-proficient colorectal cancers were mounted onto single and multiple punch tissue microarrays. Immunohistochemical quantification (score 0-3) was performed for CD3, CD4, CD8, CD45RO, CD68, CD163, FoxP3, GranzymeB, iNOS, mast cell tryptase, MUM1, PD1 and TIA-1 tumor-infiltrating (TILs) reactive cells. Coexpression experiments on fresh colorectal cancer specimens using specific cell population markers were performed. In the test group, higher numbers of CD3+ (p<0.001), CD4+ (p=0.029), CD8+ (p<0.001), CD45RO+ (p=0.048), FoxP3+ (p<0.001), GranzymeB+ (p<0.001), iNOS+ (p=0.035), MUM1+ (p=0.014), PD1+ (p=0.034) and TIA-1+ TILs (p<0.001) were linked to favourable outcome. Adjusting for age, gender, TNM stage and post-operative therapy, higher CD8+ (p<0.001; HR (95%CI): 0.66 (0.64-0.68)) and TIA-1+ (p<0.001; HR (95%CI): 0.56 (0.5-0.6)) were independent prognostic factors. Moreover, among patients with CD8+ infiltrates, TIA-1 further stratified 355 (35.6%) patients into prognostic subgroups (p<0.001; HR (95%CI): 0.89 (95%CI: 0.8-0.9)). Results were confirmed on the validation cohort (p=0.006). TIA-1+ cells were mostly CD8+ (57%), but also stained for TCRγδ (22%), CD66b (13%) and only rarely for CD4+, macrophage and NK cell markers. TIA-1 adds prognostic information to TNM stage and adjuvant therapy in MMR-proficient colorectal cancer patients. The prognostic effect of CD8+ TILs is confounded by the presence of TIA-1+ which translates into improved risk stratification for approximately 35% of all patients with MMR-proficient colorectal cancers.

Kirov R.,Bulgarian Academy of Science | Brand S.,University of Basel
Expert Review of Neurotherapeutics | Year: 2014

Sleep problems are common in attention-deficit/hyperactivity disorder (ADHD) to the extent that they mimic or exacerbate daytime symptoms expression. In this review, we advocate the need for a better understanding of sleep alterations in youths with ADHD and their impact on neurobehavioral functions including learning, memory and emotional regulation. An in-depth exploration of existing data showed that although extensively studied, the actual nature of sleep problems in ADHD and their effects on daytime behavior are still less well understood. Important issues, among which developmental changes in sleep architecture and role of subtle sleep electroencephalogram signatures, are generally neglected. Future research of sleep effects on behavior in ADHD would benefit from considering developmental aspects and links between brain activation patterns during sleep and wake. © Informa UK, Ltd.

Sick I.,University of Basel
Progress in Particle and Nuclear Physics | Year: 2012

As a consequence of the peculiar shape of the charge density ρ(r)which is close to an exponential onethe value of the proton charge rms-radius R ch determined from electron scattering data depends strongly on the density ρ(r) at large radii r. This density is poorly constrained by scattering data. Supplementing the (e, e) data with the large-r shape of ρ(r) resulting from the Fock components (n+π,...) which dominate the large-r behavior produces a more reliable value for Rch. The resulting radius agrees with the one we previously extracted from (e, e) and with the value determined from electronic Hydrogen, but disagrees with the one recently obtained from muonic Hydrogen. The origin of the discrepancy is not understood. © 2012 Elsevier B.V. All rights reserved.

Horisberger M.,University of Basel | Brunner A.,Luzerner Kantonsspital Wolhusen | Herzog R.F.,Luzerner Kantonsspital Wolhusen
Arthroscopy - Journal of Arthroscopic and Related Surgery | Year: 2010

Purpose: The aim of this study was to evaluate the short-term results after arthroscopic femoroacetabular impingement (FAI) correction combined with additional procedures addressing labral and chondral damages in patients who showed generalized severe cartilage lesions intraoperatively. Methods: Between 2004 and 2007, 20 patients (16 men and 4 women) could be included in the study. Clinical parameters, the pain score on a visual analog scale, initial radiologic degenerative changes, the alpha angle, and the Nonarthritic Hip Score were prospectively documented. The study endpoint was the implantation of a total hip arthroscopy or the latest follow-up. Results: At a mean follow-up of 3.0 years, 10 patients (50%) had undergone, or planned to undergo, total hip replacement. The remaining patients showed a significant improvement in pain, Nonarthritic Hip Score, and hip flexion and internal rotation. Conclusions: In patients with already marked generalized chondral lesions, arthroscopy does not have any effect beyond the short-term pain relief resulting from debridement. The study underlines the fact that FAI with advanced osteoarthrosis, particularly Tönnis grade III, is not an indication for arthroscopic FAI correction. Level of Evidence: Level IV, therapeutic case series. © 2010 Arthroscopy Association of North America.

Tyrosine kinase inhibitors represent today’s treatment of choice in chronic myeloid leukemia (CML). Allogeneic hematopoietic stem cell transplantation (HSCT) is regarded as salvage therapy. This prospective randomized CML-study IIIA recruited 669 patients with newly diagnosed CML between July 1997 and January 2004 from 143 centers. Of these, 427 patients were considered eligible for HSCT and were randomized by availability of a matched family donor between primary HSCT (group A; N=166 patients) and best available drug treatment (group B; N=261). Primary end point was long-term survival. Survival probabilities were not different between groups A and B (10-year survival: 0.76 (95% confidence interval (CI): 0.69–0.82) vs 0.69 (95% CI: 0.61–0.76)), but influenced by disease and transplant risk. Patients with a low transplant risk showed superior survival compared with patients with high- (P<0.001) and non-high-risk disease (P=0.047) in group B; after entering blast crisis, survival was not different with or without HSCT. Significantly more patients in group A were in molecular remission (56% vs 39%; P=0.005) and free of drug treatment (56% vs 6%; P<0.001). Differences in symptoms and Karnofsky score were not significant. In the era of tyrosine kinase inhibitors, HSCT remains a valid option when both disease and transplant risk are considered.Leukemia advance online publication, 20 November 2015; doi:10.1038/leu.2015.281. © 2015 Macmillan Publishers Limited

Pentassuglia L.,University of Basel | Sawyer D.B.,Vanderbilt University
Biochimica et Biophysica Acta - Molecular Cell Research | Year: 2013

Neuregulin (Nrg)/ErbB and integrin signaling pathways are critical for the normal function of the embryonic and adult heart. Both systems activate several downstream signaling pathways, with different physiological outputs: cell survival, fibrosis, excitation-contraction coupling, myofilament structure, cell-cell and cell-matrix interaction. Activation of ErbB2 by Nrg1β in cardiomycytes or its overexpression in cancer cells induces phosphorylation of FAK (Focal Adhesion Kinase) at specific sites with modulation of survival, invasion and cell-cell contacts. FAK is also a critical mediator of integrin receptors, converting extracellular matrix alterations into intracellular signaling. Systemic FAK deletion is lethal and is associated with left ventricular non-compaction whereas cardiac restriction in adult hearts is well tolerated. Nevertheless, these hearts are more susceptible to stress conditions like trans-aortic constriction, hypertrophy, and ischemic injury. As FAK is both downstream and specifically activated by integrins and Nrg-1β, here we will explore the role of FAK in the heart as a protective factor and as possible mediator of the crosstalk between the ErbB and Integrin receptors. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Cardiac Pathways of Differentiation, Metabolism and Contraction. © 2012 Elsevier B.V.

Choukrallah M.A.,Friedrich Miescher Institute for Biomedical Research | Matthias P.,Friedrich Miescher Institute for Biomedical Research | Matthias P.,University of Basel
Frontiers in Immunology | Year: 2014

All mature blood cells derive from hematopoietic stem cells through gradual restriction of their cell fate potential and acquisition of specialized functions. Lineage specification and cell commitment require the establishment of specific transcriptional programs involving the activation of lineage-specific genes and the repression of lineage-inappropriate genes. This process requires the concerted action of transcription factors (TFs) and epigenetic modifying enzymes. Within the hematopoietic system, B lymphopoiesis is one of the most-studied differentiation programs. Loss of function studies allowed the identification of many TFs and epigenetic modifiers required for B cell development. The usage of systematic analytical techniques such as transcriptome determination, genome-wide mapping of TF binding and epigenetic modifications, and mass spectrometry analyses, allowed to gain a systemic description of the intricate networks that guide B cell development. However, the precise mechanisms governing the interaction between TFs and chromatin are still unclear. Generally, chromatin structure can be remodeled by some TFs but in turn can also regulate (i.e., prevent or promote) the binding of other TFs. This conundrum leads to the crucial questions of who is on first, when, and how. We review here the current knowledge about TF networks and epigenetic regulation during hematopoiesis, with an emphasis on B cell development, and discuss in particular the current models about the interplay between chromatin and TFs. © 2014 Choukrallah and Matthias.

Wootton J.R.,University of Basel
Physical Review A - Atomic, Molecular, and Optical Physics | Year: 2013

Recent studies have shown that topological models with interacting anyonic quasiparticles can be used as self-correcting quantum memories. Here we study the behavior of these models at thermal equilibrium. It is found that the interactions allow topological order to exist at finite temperature, not only in an extension of the ground-state phase, but also in a novel form of topologically ordered phase. Both phases are found to support self-correction in all models considered, and the transition between them corresponds to a change in the scaling of memory lifetime with system size. © 2013 American Physical Society.

In the past 15 years, more than 1,500 patients worldwide have received a hematopoietic stem cell transplant, mostly autologous, as treatment for a severe autoimmune disease (AD). A recent retrospective analysis of 900 patients showed that the majority had multiple sclerosis, systemic sclerosis, systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and juvenile idiopathic arthritis (JIA; n = 65) and idiopathic cytopenic purpura. An overall 85% 5-year survival and 43% progression-free survival was seen, with 100-day transplant-related mortality (TRM) ranging between 1% (RA) and 11% (SLE and JIA). Around 30% of patients in all disease subgroups had a complete response, despite full immune reconstitution. In many patients, morphological improvement was documented beyond any predicted known effects of intense immunosuppression alone. It is hoped that the results of three ongoing large prospective, randomized, controlled trials will allow modification of the protocols to reduce the high TRM, which relates to regimen intensity, age of patient, and comorbidity. Multipotent mesenchymal stromal cells (MSCs), including autologous MSCs, have recently been tested in various ADs, exploiting their immune-modulating properties and apparent low acute toxicity. Despite encouraging small phase I/II studies, no positive data from randomized, prospective studies are as yet available in the peer-reviewed literature.

Autologous hematopoietic stem cell transplantation (HSCT) has been used to treat severe and refractory autoimmune diseases (ADs) in children and adults for more than 15 years. The aim of this treatment is to restore tolerance through an intense lymphodepleting conditioning, and many patients have achieved lasting remissions. However, HSCT is associated with significant morbidity and mortality and is therefore not yet standard of care. Pre-existing reduced organ function of patients with ADs may increase the organ toxicity of conditioning. In the early post-HSCT phase, bacterial or fungal infections occur and therapy-associated lymphopenia sets patients at risk for reactivation of endogenous viruses and other opportunistic infections. During re-emerging of lymphopoiesis after HSCT, de novo autoimmunity may develop through loss of central or peripheral control mechanisms. Late effects of autologous HSCT (e.g., on the endocrine system) and a potentially increased frequency of secondary malignancies are of concern. The steadily increasing knowledge about specific complications occurring in patients with ADs after HSCT has led to the adaption of treatment protocols and has already reduced toxicity. Further prospective long-term follow-up studies are needed to identify patients at risk for developing serious complications after HSCT.

Sutter R.,Johns Hopkins University | Sutter R.,University of Basel | Kaplan P.W.,Johns Hopkins Bayview Medical Center
Epilepsia | Year: 2012

There have been many attempts at defining the electroencephalography (EEG) characteristics of nonconvulsive status epilepticus (NCSE) without a universally accepted definition. This lack of consensus arises because the EEG expression of NCSE does not exist in isolation, but reflects status epilepticus under the variety of pathologic conditions that occur with age, cerebral development, encephalopathy, and epilepsy syndrome. Current NCSE definitions include "boundary conditions," in which electroencephalographic seizure activity occurs without apparent clinical seizures. Furthermore, what appears to one interpreter as status epilepticus, is not to another reader, reflecting the "art" of EEG interpretation. Seizures and epilepsy syndromes have undergone an evolution that has moved beyond a classification of focal or generalized conditions into a syndromic approach. It seems appropriate to make similar changes in the EEG analysis of the syndromes of NCSE. In effect, the literature on epilepsy classification has progressed to incorporate the different NCSE types with clinical descriptions, but the specific EEG evidence for these types is found largely in individual reports, and often by description only. NCSE classification of EEG patterns should derive from the aggregate of published EEG patterns in the respective clinical subtype, supported by an analysis of these EEG studies. The analysis that follows presents clinical descriptions and EEG patterns of NCSE in the neonatal period, infancy, childhood, adulthood, and late adulthood from a syndromic perspective based on age, encephalopathy, cerebral development, etiology, and syndrome. Proceeding from the proposed classification of status epilepticus syndromes in "Status epilepticus: its clinical features and treatment in children and adults" (published in 1994 by Cambridge University Press, New York), we have performed a systematic search for reports presenting EEG patterns of NCSE using the online medical search engine PubMed for 22 different search strategies. EEG patterns were reviewed by two board-certified epileptologists who reached consensus regarding presence of NCSE. From a total of 4,328 search results, 123 cases with corresponding EEG patterns could be allocated to underlying epilepsy syndromes. Typical characteristic, prominent electrographic patterns, and sequential arrangements are elucidated for the different NCSE syndromes. This compendium of patterns by NCSE syndrome classification with illustration of EEGs, and delineation of electroencephalographic features helps define the characteristics and semiologic borderlines among the types of NCSE. © Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.

Trifunovic L.,University of Basel
Physical Review Letters | Year: 2011

We consider a long superconductor-ferromagnet-superconductor junction with one spin-active region. It is shown that an odd number of Cooper pairs cannot have a long-range propagation when there is only one spin-active region. When the temperature is much lower than the Thouless energy, the coherent transport of two Cooper pairs becomes the dominant process and the superharmonic current-phase relation is obtained (I2). © 2011 American Physical Society.

Wegner H.A.,University of Basel
Angewandte Chemie - International Edition | Year: 2012

Two bands make light work: Since the isomerization of azobenzenes is usually induced by UV light, its application is limited in living systems. A new azobenzene switch now operates entirely in the visible range. The new design is based on the introduction of OMe groups in the ortho positions, which splits the n-π* transition into two absorption bands. The two isomeric forms can be obtained with more than 80% enrichment from the respective photostationary state. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Cabane E.,University of Basel
Biointerphases | Year: 2012

This review focuses on smart nano-materials built of stimuli-responsive (SR) polymers and will discuss their numerous applications in the biomedical field. The authors will first provide an overview of different stimuli and their corresponding, responsive polymers. By introducing myriad functionalities, SR polymers present a wide range of possibilities in the design of stimuli-responsive devices, making use of virtually all types of polymer constructs, from self-assembled structures (micelles, vesicles) to surfaces (polymer brushes, films) as described in the second section of the review. In the last section of this review the authors report on some of the most promising applications of stimuli-responsive polymers in nanomedicine. In particular, we will discuss applications pertaining to diagnosis, where SR polymers are used to construct sensors capable of selective recognition and quantification of analytes and physical variables, as well as imaging devices. We will also highlight some examples of responsive systems used for therapeutic applications, including smart drug delivery systems (micelles, vesicles, dendrimers...) and surfaces for regenerative medicine.

Gerber M.,University of Basel
Medicine and Science in Sports and Exercise | Year: 2016

PURPOSE: This cross-sectional observational study examined the degree to which cardiorespiratory fitness (CRF) and self-perceived stress are associated with cardiometabolic risk factors and the overall risk score for cardiovascular diseases. The second aim was to determine whether participants’ CRF levels moderate the relationships between stress and cardiometabolic risk. METHODS: A gender-matched stratified sample (N=197, 51% men, Mage=39.2 years) was used to ensure that participants with varying stress levels were equally represented. CRF was assessed with the Åstrand bicycle test, perceived stress with a single-item question. Systolic (SBP) and diastolic blood pressure (DBP), body mass index (BMI), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triglycerides (TG), and glycated hemoglobin (HbA1c), and a total cardiometabolic risk score (sum of the z-standardized residuals of the above indicators) were assessed as outcomes. RESULTS: Higher LDL-C, TG, and total metabolic risk were found in participants with high stress scores (p<.05). In addition, lower SBP, DBP, BMI, LDL-C, TG, and total metabolic risk were observed in participants with high CRF (p<.05). Two-way analyses of covariance provided significant interaction effects for five of the nine outcome variables (p<.05, 3.6%-4.8% of explained variance). Participants with high stress who also had high CRF levels had lower SBP, DBP, LDL-C, TG, and total cardiometabolic risk than participants with high stress, but low or moderate CRF levels. No significant main or interaction effects occurred for BMI, TC, HDL-C, and HbA1c. CONCLUSION: Better CRF is associated with more favourable levels of several cardiometabolic risk factors, specifically in participants experiencing high stress. Higher CRF may provide some protection against the health hazards of high chronic stress by attenuating the stress-related increase in cardiovascular risk factors. © 2016 American College of Sports Medicine

Langewitz W.,University of Basel
Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz | Year: 2012

Based on a review of recent key articles, this paper demonstrates that many elements of physician-patient communication can be learned successfully during medical education. Methods of assessment and definition of success depend largely on the definition of teaching goals, which are usually based on the principles of a more egalitarian and non-paternalistic physician-patient communication. In this article another approach is suggested. Teaching objectives in patient-physician communication can also be deduced from the needs of clinical medicine, resulting in the following goals: students are able to gather relevant data from patients' history, they explicitly structure the consultation and the way they give information, they know how to respond to patients' emotions. The Objective Standardised Clinical Examination (OSCE) is discussed with its strengths and weaknesses. The inclusion of video-based feedback is presented as a teaching tool to improve students' self-reflection. Workplace-based assessment and Mini-CEX are promising educational tools that require a well-trained faculty, not only in the teaching and practice of communication but also in the art of giving constructive and yet honest feedback. © Springer-Verlag 2012.

Bravyi S.,IBM | DiVincenzo D.P.,RWTH Aachen | Loss D.,University of Basel
Annals of Physics | Year: 2011

The Schrieffer-Wolff (SW) method is a version of degenerate perturbation theory in which the low-energy effective Hamiltonian Heff is obtained from the exact Hamiltonian by a unitary transformation decoupling the low-energy and high-energy subspaces. We give a self-contained summary of the SW method with a focus on rigorous results. We begin with an exact definition of the SW transformation in terms of the so-called direct rotation between linear subspaces. From this we obtain elementary proofs of several important properties of Heff such as the linked cluster theorem. We then study the perturbative version of the SW transformation obtained from a Taylor series representation of the direct rotation. Our perturbative approach provides a systematic diagram technique for computing high-order corrections to Heff. We then specialize the SW method to quantum spin lattices with short-range interactions. We establish unitary equivalence between effective low-energy Hamiltonians obtained using two different versions of the SW method studied in the literature. Finally, we derive an upper bound on the precision up to which the ground state energy of the nth-order effective Hamiltonian approximates the exact ground state energy. © 2011 Elsevier Inc.

Zumsteg A.,University of Basel
Cold Spring Harbor perspectives in medicine | Year: 2012

The lymphatic vascular system and the hematopoietic system are intimately connected in ontogeny and in physiology. During embryonic development, mammalian species derive a first lymphatic vascular plexus from the previously formed anterior cardinal vein, whereas birds and amphibians have a lymphatic vascular system of dual origin, composed of lymphatic endothelial cells (LECs) of venous origin combined with LECs derived from mesenchymal lymphangioblasts. The contribution of hematopoietic cells as building blocks of nascent lymphatic structures in mammals is still under debate. In contrast, the importance of myeloid cells to direct lymphatic vessel growth and function postnatally has been experimentally shown. For example, myeloid cells communicate with LECs via paracrine factors or cell-cell contacts, and they also can acquire lymphatic endothelial morphology and marker gene expression, a process reminiscent of developmental vasculogenesis. Here, we present an overview of the current understanding of how lymphatic vessels and the hematopoietic system, in particular myeloid cells, interact during embryonic development, in normal organ physiology, and in disease.

Schmid S.M.,University of Basel
Archives of gynecology and obstetrics | Year: 2011

In the western world, cannabis is the most widely used drug of abuse. Cannabinoid hyperemesis syndrome, which seems to be a rare paradoxical reaction in individuals with a particular predisposition, is characterized by cyclic severe nausea and vomiting in long-term cannabis users. While the symptoms are unresponsive to antiemetic drugs, compulsive hot baths result in a considerable symptom relief. We report the first case of cannabinoid hyperemesis syndrome in pregnancy. A 26-year-old patient was admitted to our clinic in the 10th week of gestation. Before undertaking time-consuming and expensive medical examinations to rule out other medical reasons for therapy-resistant hyperemesis in pregnancy, obstetricians should determine whether compulsive bathing or showering provides symptomatic relief and ask specific questions regarding possible/suspected cannabis consumption.

Schmidt M.J.,RWTH Aachen | Schmidt M.J.,University of Basel
Physical Review B - Condensed Matter and Materials Physics | Year: 2012

A bosonic field theory is derived for the tunable edge magnetism at graphene zigzag edges. The derivation starts from an effective fermionic theory for the interacting graphene edge states, derived previously from a two-dimensional Hubbard model for graphene. The essential feature of this effective model, which gives rise to the weak edge magnetism, is the momentum-dependent nonlocal electron-electron interaction. It is shown that this momentum dependence may be treated by an extension of the bosonization technique and leads to interactions of the bosonic fields. These interactions are reminiscent of a φ4 field theory. Focusing on the regime close to the quantum phase transition between the ferromagnetic and the paramagnetic Luttinger liquid, a semiclassical interpretation of the interacting bosonic theory is given. Furthermore, it is argued that the universal critical behavior at the quantum phase transition between the paramagnetic and the ferromagnetic Luttinger liquid is governed by a small number of terms in this theory, which are accessible by quantum Monte Carlo methods. © 2012 American Physical Society.

Cavelti-Weder C.,University of Basel
Molecular Therapy | Year: 2015

Interleukin-1β (IL-1β) is a key cytokine involved in inflammatory illnesses including rare hereditary diseases and common chronic inflammatory conditions as gout, rheumatoid arthritis, and type 2 diabetes mellitus, suggesting reduction of IL-1β activity as new treatment strategy. The objective of our study was to assess safety, antibody response, and preliminary efficacy of a novel vaccine against IL-1β. The vaccine hIL1bQb consisting of full-length, recombinant IL-1β coupled to virus-like particles was tested in a preclinical and clinical, randomized, placebo-controlled, double-blind study in patients with type 2 diabetes. The preclinical simian study showed prompt induction of IL-1β-specific antibodies upon vaccination, while neutralizing antibodies appeared with delay. In the clinical study with 48 type 2 diabetic patients, neutralizing IL-1β-specific antibody responses were detectable after six injections with doses of 900 µg. The development of neutralizing antibodies was associated with higher number of study drug injections, lower baseline body mass index, improvement of glycemia, and C-reactive protein (CRP). The vaccine hIL1bQb was safe and well-tolerated with no differences regarding adverse events between patients receiving hIL1bQb compared to placebo. This is the first description of a vaccine against IL-1β and represents a new treatment option for IL-1β-dependent diseases such as type 2 diabetes mellitus (ClinicalTrials.gov NCT00924105).Molecular Therapy (2016); doi:10.1038/mt.2015.227. © 2015 American Society of Gene & Cell Therapy

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.

Nigg E.A.,University of Basel | Stearns T.,Stanford University
Nature Cell Biology | Year: 2011

Centrosomes are microtubule-organizing centres of animal cells. They influence the morphology of the microtubule cytoskeleton, function as the base for the primary cilium and serve as a nexus for important signalling pathways. At the core of a typical centrosome are two cylindrical microtubule-based structures termed centrioles, which recruit a matrix of associated pericentriolar material. Cells begin the cell cycle with exactly one centrosome, and the duplication of centrioles is constrained such that it occurs only once per cell cycle and at a specific site in the cell. As a result of this duplication mechanism, the two centrioles differ in age and maturity, and thus have different functions; for example, the older of the two centrioles can initiate the formation of a ciliary axoneme. We discuss spatial aspects of the centrosome duplication cycle, the mechanism of centriole assembly and the possible consequences of the inherent asymmetry of centrioles and centrosomes. © 2011 Macmillan Publishers Limited. All rights reserved.

Stadelmann P.,University of Basel
Schweizer Monatsschrift für Zahnmedizin = Revue mensuelle suisse d'odonto-stomatologie = Rivista mensile svizzera di odontologia e stomatologia / SSO | Year: 2012

Since the first survey in 1992/93, the Swiss Health Survey (SHS) has been repeated every 5 years (1997, 2002 and 2007). In the present study, dental visits (dental care utilisation within the last 12 months), oral hygiene measures and the frequency of orthodontic treatments in the Swiss population in 2002 were examined and dental visits were compared with the years 1992/93, 1997 and 2007. Weighted data were analysed regarding different sociodemographic factors. From 1992 to 2002, dental visits among the 15-74-year-old declined continuously (1992/93: 70%, 1997: 66%, 2002: 63%), whereas in 2007 a slight increase (66%) was documented. In the survey from 2002, a large proportion (74%) of the population stated to clean their teeth or prostheses several times a day, predominantly with a manual toothbrush, whereas 28% applied an electric toothbrush and almost half of the respondents also used dental floss or toothpicks. Fewer visits and less intensive oral hygiene measures were observed among the elderly, men, weak social strata, smokers, persons with more than 8 missing teeth and in the group with removable dentures. Almost a quarter of the population had orthodontic treatment with the highest proportion among the 15-24-year-old (56%).

Papadopoulou A.,University of Basel
Expert review of clinical pharmacology | Year: 2012

Teriflunomide, the active metabolite of an approved antirheumatic drug, is an emerging oral therapy for multiple sclerosis (MS). Next to the inhibition of pyrimidine biosynthesis and proliferation of activated lymphocytes, it seems to have multiple anti-inflammatory and immunomodulating effects. Phase II and III clinical trials in relapsing MS demonstrated favorable safety and tolerability of the drug, as well as clinical efficacy, with a significant reduction of relapse rate, comparable with those of the available injectable immunomodulatory agents. While multiple other studies with teriflunomide are currently ongoing, its exact place in future treatment algorithms for MS is difficult to predict. It may be a good alternative for patients wishing to have an oral treatment with relatively large data regarding long-term safety.

The Intercontinental Cooperative ITP Study Group (ICIS) was founded in 1997, when the American practice guidelines demonstrated that there is a substantial lack of clinical data. The aim of the group was to promote basic science and clinical research in the field of ITP. Clinical data and more recently DNA is collected to investigate children and adults with ITP. ICIS organizes regular meetings and opened several registries, the most recent being the Pediatric and Adult Registry on Chronic ITP (PARC-ITP), all of which will be briefly discussed. There are many unanswered questions in basic science and clinical research in ITP which need large collaborative studies. The international network of ICIS may be of value in better understanding ITP. © 2012 Wiley Periodicals, Inc.

Bonjour J.-P.,University of Geneva | Benoit V.,Yoplait | Payen F.,Yoplait | Kraenzlin M.,University of Basel
Journal of Clinical Endocrinology and Metabolism | Year: 2013

Context: Nutritional prevention of bone deterioration with fortified foods seems particularly suitable in institutionalized elderly women at risk of vitamin D deficiency, secondary hyperparathyroidism, increased bone resorption, and osteoporotic fracture. Objective: The objective was to evaluate whether fortification of yogurts with vitamin D and calcium exerts an additional lowering effect on serum PTH and bone resorption markers as compared with isocaloric and isoprotein dairy products in elderly women. Design: A randomized double-blind controlled-trial, 56-day intervention was conducted in institutionalized women (mean age 85.5 years) consuming 2 125-g servings of either vitamin D- and calcium-fortified yogurt (FY) at supplemental levels of 10 μg/d vitamin D3 and 800 mg/d calcium or nonfortified control yogurt (CY) providing 280 mg/d calcium. Main Outcomes: The endpoints were serum changes from baseline (day 0) to day 28 and day 56 in 25-hydroxyvitamin-D (25OHD), PTH, and bone resorption markers tartrate-resistant acid phosphatase isoform-5b (TRAP5b), the primary outcome, and carboxyl-terminal cross-linked telopeptide of type I collagen (CTX). Results: At day 56, serum 25OHD increased (mean ± SEM) by 25.3 ± 1.8 vs 5.2 ± 2.5 nmol/L in FY (n = 29) and CY (n = 27), respectively (P < .0001). The corresponding changes in PTH were -28.6% ± 7.2% vs -8.0% ± 4.3% (P = .0003); in TRAP5b, -21.9% ± 4.3% vs 3.0% ± 3.2% (P < .0001); and in CTX, -11.0% ± 9.7% vs -3.0% ± 4.1% (P = .0146), in FY and CY, respectively. At day 28, these differences were less pronounced but already significant for 25OHD, PTH, and TRAP5b. Conclusions: This study in institutionalized elderly at high risk for osteoporotic fracture suggests that fortification of dairy products with vitamin D3 and calcium provides a greater prevention of accelerated bone resorption as compared with nonfortified equivalent foods. Copyright © 2013 by The Endocrine Society.

Bolander B.,University of Basel
Journal of Pragmatics | Year: 2012

In this paper, I focus on responsiveness in 185 disagreements and 219 agreements in the comments sections of eight personal/diary blogs. Since the message format of personal/diary blogs is such that responsiveness is not signalled by the system, interlocutors need to make manifest to whom a disagreement or agreement is directed. Bloggers and readers are likely to make use of a variety of means of signaling responsiveness, such as naming, format tying (Muntigl and Turnbull, 1998) and quoting. The are not likely to rely extensively on quoting, as they might in modes in which quoting constitutes a built-in technological property. My analysis of disagreements and agreements highlights that while responsiveness is integral to agreements and disagreements, it does not have to be made explicit in personal/diary blog interactions. I argue that explicitness appears to be associated with the participation framework of blogs, such that there is a greater need to signal responsiveness explicitly when readers address other readers, but a smaller need to signal responsiveness explicitly when readers address bloggers. The paper thus demonstrates how particular social (participation framework) and medium factors (message format and quoting) (Herring, 2007) are tied with the linguistic realisation of disagreements and agreements. © 2012 Elsevier B.V.

Baker N.,London School of Hygiene and Tropical Medicine | de Koning H.P.,University of Glasgow | Maser P.,Swiss Tropical and Public Health Institute | Maser P.,University of Basel | Horn D.,London School of Hygiene and Tropical Medicine
Trends in Parasitology | Year: 2013

Melarsoprol and pentamidine represent the two main classes of drugs, the arsenicals and diamidines, historically used to treat the diseases caused by African trypanosomes: sleeping sickness in humans and Nagana in livestock. Cross-resistance to these drugs was first observed over 60 years ago and remains the only example of cross-resistance among sleeping sickness therapies. A Trypanosoma brucei adenosine transporter is well known for its role in the uptake of both drugs. More recently, aquaglyceroporin 2 (AQP2) loss of function was linked to melarsoprol-pentamidine cross-resistance. AQP2, a channel that appears to facilitate drug accumulation, may also be linked to clinical cases of resistance. Here, we review these findings and consider some new questions as well as future prospects for tackling the devastating diseases caused by these parasites. © 2013 Elsevier Ltd.

McVicar T.R.,CSIRO | Korner C.,University of Basel
Oecologia | Year: 2013

Effective communication regarding distance in the vertical dimension is critical for many ecological, climatological and broader geophysical studies of the Earth. Confusion exists regarding the definition of three English words commonly used to describe the vertical dimension: (1) elevation; (2) altitude; and (3) height. While used interchangeably in "everyday" non-technical English, here we provide explicit definitions and strongly recommend their use in scientific literature. We briefly discuss the likely origins of the sub-optimal use of these three words due to translations between languages. Finally, we provide examples of how using these terms, as explicitly defined herein, improves scientific communication. © 2012 Springer-Verlag.

Hammer J.,University of Basel
Paediatric Respiratory Reviews | Year: 2013

Acute respiratory failure is the most common medical emergency in children. One aim of this review is to discuss the physiologic peculiarities that explain the increased vulnerability of infants and children to any pathology affecting the respiratory tract. The other aim is to highlight the importance of history taking and correct physical examination for early recognition of an impending catastrophic progression of respiratory failure. Under most circumstances, correct physical examination alone allows one to pinpoint the cause to a particular part of the respiratory system and to make the appropriate decisions for a proactive and life-saving management of the critically ill child. © 2013 Elsevier Ltd.

Bieri O.,University of Basel | Scheffler K.,Max Planck Institute for Biological Cybernetics | Scheffler K.,University of Tubingen
Journal of Magnetic Resonance Imaging | Year: 2013

Balanced steady state free precession (balanced SSFP) has become increasingly popular for research and clinical applications, offering a very high signal-to-noise ratio and a T2/T1-weighted image contrast. This review article gives an overview on the basic principles of this fast imaging technique as well as possibilities for contrast modification. The first part focuses on the fundamental principles of balanced SSFP signal formation in the transient phase and in the steady state. In the second part, balanced SSFP imaging, contrast, and basic mechanisms for contrast modification are revisited and contemporary clinical applications are discussed. © 2013 Wiley Periodicals, Inc.

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.

Stoeber M.,ETH Zurich | Stoeck I.K.,ETH Zurich | HeCurrency Signnni C.,ETH Zurich | Bleck C.K.E.,University of Basel | And 2 more authors.
EMBO Journal | Year: 2012

Caveolae are specialized domains present in the plasma membrane (PM) of most mammalian cell types. They function in signalling, membrane regulation, and endocytosis. We found that the Eps-15 homology domain-containing protein 2 (EHD2, an ATPase) associated with the static population of PM caveolae. Recruitment to the PM involved ATP binding, interaction with anionic lipids, and oligomerization into large complexes (60ĝ€"75S) via interaction of the EH domains with intrinsic NPF/KPF motifs. Hydrolysis of ATP was essential for binding of EHD2 complexes to caveolae. EHD2 was found to undergo dynamic exchange at caveolae, a process that depended on a functional ATPase cycle. Depletion of EHD2 by siRNA or expression of a dominant-negative mutant dramatically increased the fraction of mobile caveolar vesicles coming from the PM. Overexpression of EHD2, in turn, caused confinement of cholera toxin B in caveolae. The confining role of EHD2 relied on its capacity to link caveolae to actin filaments. Thus, EHD2 likely plays a key role in adjusting the balance between PM functions of stationary caveolae and the role of caveolae as vesicular carriers. © 2012 European Molecular Biology Organization.

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.

Broz P.,University of Basel
Cell Host and Microbe | Year: 2014

Two reports in this issue of Cell Host & Microbe (Sellin et al., 2014; Knodler et al., 2014) establish the cell-intrinsic inflammasome-induced extrusion of infected enterocytes as a general defense mechanism against acute bacterial infections. © 2014 Elsevier Inc.

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.

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.

Skoda R.C.,University of Basel
Blood | Year: 2014

In this issue of Blood, Meyer et al report that deleting Jak2 selectively in megakaryocytes and platelets results in an unexpected thrombocytosis phenotype. Their results demonstrate that Jak2 is dispensable for megakaryocyte differentiation and platelet formation but is required for suppressing circulating thrombopoietin (Tpo). © 2014 by The American Society of Hematology.

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.

Comas I.,UK National Institute for Medical Research | Chakravartti J.,New York University | Small P.M.,Bill and Melinda Gates Foundation | Galagan J.,The Broad Institute of MIT and Harvard | And 6 more authors.
Nature Genetics | Year: 2010

Mycobacterium tuberculosis is an obligate human pathogen capable of persisting in individual hosts for decades. We sequenced the genomes of 21 strains representative of the global diversity and six major lineages of the M. tuberculosis complex (MTBC) at 40-to 90-fold coverage using Illumina next-generation DNA sequencing. We constructed a genome-wide phylogeny based on these genome sequences. Comparative analyses of the sequences showed, as expected, that essential genes in MTBC were more evolutionarily conserved than nonessential genes. Notably, however, most of the 491 experimentally confirmed human T cell epitopes showed little sequence variation and had a lower ratio of nonsynonymous to synonymous changes than seen in essential and nonessential genes. We confirmed these findings in an additional data set consisting of 16 antigens in 99 MTBC strains. These findings are consistent with strong purifying selection acting on these epitopes, implying that MTBC might benefit from recognition by human T cells. © 2010 Nature America, Inc. All rights reserved.

Krusche B.,University of Basel
Journal of Physics: Conference Series | Year: 2012

Recent results for the photoproduction of mesons from nuclei with tagged bremsstrahlung beams are summarized. The experiments have been done at the Mainz MAMI accelerator with the Crystal Ball/TAPS setup and at the Bonn ELSA accelerator with the Crystal Barrel/TAPS detector. Two main physics topics are covered. The electromagnetic excitation spectrum of the neutron has been studied with meson photoproduction reactions off quasi-free neutrons from light nuclei. Particularly interesting results have been obtained for η-photoproduction, where the excitation function of the neutron shows a pronounced, narrow structure which is not observed for the proton. The interaction of mesons with nuclear matter and the in-medium properties of hadrons under various aspects have been studied with meson photoproduction from nuclei, covering a large mass range (from the deuteron to lead). Questions like the possible formation of η-mesic nuclei and in-medium modifications of the σ-meson have been addressed.

Nyffeler M.,University of Basel | Knornschild M.,University of Ulm
PLoS ONE | Year: 2013

In this paper more than 50 incidences of bats being captured by spiders are reviewed. Bat-catching spiders have been reported from virtually every continent with the exception of Antarctica (~90% of the incidences occurring in the warmer areas of the globe between latitude 30° N and 30° S). Most reports refer to the Neotropics (42% of observed incidences), Asia (28.8%), and Australia-Papua New Guinea (13.5%). Bat-catching spiders belong to the mygalomorph family Theraphosidae and the araneomorph families Nephilidae, Araneidae, and Sparassidae. In addition to this, an attack attempt by a large araneomorph hunting spider of the family Pisauridae on an immature bat was witnessed. Eighty-eight percent of the reported incidences of bat catches were attributable to web-building spiders and 12% to hunting spiders. Large tropical orb-weavers of the genera Nephila and Eriophora in particular have been observed catching bats in their huge, strong orb-webs (of up to 1.5 m diameter). The majority of identifiable captured bats were small aerial insectivorous bats, belonging to the families Vespertilionidae (64%) and Emballonuridae (22%) and usually being among the most common bat species in their respective geographic area. While in some instances bats entangled in spider webs may have died of exhaustion, starvation, dehydration, and/or hyperthermia (i.e., non-predation death), there were numerous other instances where spiders were seen actively attacking, killing, and eating the captured bats (i.e., predation). This evidence suggests that spider predation on flying vertebrates is more widespread than previously assumed. © 2013 Nyffeler, Knörnschild.

Ebert D.,University of Basel
Annual Review of Ecology, Evolution, and Systematics | Year: 2013

Vertical and horizontal transmission are terms that describe the transfer of symbionts from parents to offspring and among unrelated hosts, respectively. Many symbionts, including parasites, pathogens, mutualists, and microbiota, use a combination of both strategies, known as mixed-mode transmission (MMT). Here I review what is known about the evolution, ecology, and epidemiology of symbionts with MMT and compare MMT with our expectations for single-mode strategies. Symbionts with MMT are common and, in comparison with single-mode symbionts, show many surprising features. MMT combines the best of two worlds with regard to the ecological conditions required for persistence and plays a role in the evolution of virulence and genome architecture. Even rare transmission by the minority type of these two transmission modes can make a big difference for the system. This review explores the conceptual issues surrounding the dynamics of mixed-mode symbionts by reviewing literature from the entire range of host and symbiont taxa. © Copyright ©2013 by Annual Reviews. All rights reserved.

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.

Ward T.R.,University of Basel
Accounts of Chemical Research | Year: 2011

Artificial metalloenzymes are created by incorporating an organometallic catalyst within a host protein. The resulting hybrid can thus provide access to the best features of two distinct, and often complementary, systems: homogeneous and enzymatic catalysts. The coenzyme may be positioned with covalent, dative, or supramolecular anchoring strategies. Although initial reports date to the late 1970s, artificial metalloenzymes for enantioselective catalysis have gained significant momentum only in the past decade, with the aim of complementing homogeneous, enzymatic, heterogeneous, and organic catalysts. Inspired by a visionary report by Wilson and Whitesides in 1978, we have exploited the potential of biotin - avidin technology in creating artificial metalloenzymes. Owing to the remarkable affinity of biotin for either avidin or streptavidin, covalent linking of a biotin anchor to a catalyst precursor ensures that, upon stoichiometric addition of (strept)avidin, the metal moiety is quantitatively incorporated within the host protein. In this Account, we review our progress in preparing and optimizing these artificial metalloenzymes, beginning with catalytic hydrogenation as a model and expanding from there. These artificial metalloenzymes can be optimized by both chemical (variation of the biotin - spacer - ligand moiety) and genetic (mutation of avidin or streptavidin) means. Such chemogenetic optimization schemes were applied to various enantioselective transformations. The reactions implemented thus far include the following: (i) The rhodium-diphosphine catalyzed hydrogenation of N-protected dehydroaminoacids (ee up to 95%); (ii) the palladium-diphosphine catalyzed allylic alkylation of 1,3-diphenylallylacetate (ee up to 95%); (iii) the ruthenium pianostool-catalyzed transfer hydrogenation of prochiral ketones (ee up to 97% for aryl-alkyl ketones and ee up to 90% for dialkyl ketones); (iv) the vanadyl-catalyzed oxidation of prochiral sulfides (ee up to 93%). A number of noteworthy features are reminiscent of homogeneous catalysis, including straightforward access to both enantiomers of the product, the broad substrate scope, organic solvent tolerance, and an accessible range of reactions that are typical of homogeneous catalysts. Enzyme-like features include access to genetic optimization, an aqueous medium as the preferred solvent, Michaelis - Menten behavior, and single-substrate derivatization. The X-ray characterization of artificial metalloenzymes provides fascinating insight into possible enantioselection mechanisms involving a well-defined second coordination sphere environment. Thus, such artificial metalloenzymes combine attractive features of both homogeneous and enzymatic kingdoms. In the spirit of surface borrowing, that is, modulating ligand affinity by harnessing existing protein surfaces, this strategy can be extended to selectively binding streptavidin-incorporated biotinylated ruthenium pianostool complexes to telomeric DNA. This application paves the way for chemical biology applications of artificial metalloenzymes. © 2010 American Chemical Society.

Spiess M.,University of Basel
Current Biology | Year: 2014

The Sec61/SecYEG complex mediates both the translocation of newly synthesized proteins across the membrane and the integration of transmembrane segments into the lipid bilayer. New cryo-electron microscopy studies show ribosome-channel complexes in action and reveal their repertoire of conformational states. © 2014 Elsevier Ltd. All rights reserved.

Schwede T.,University of Basel | Schwede T.,Swiss Institute of Bioinformatics
Structure | Year: 2013

Computational modeling of three-dimensional macromolecular structures and complexes from their sequence has been a long-standing vision in structural biology. Over the last 2 decades, a paradigm shift has occurred: starting from a large "structure knowledge gap" between the huge number of protein sequences and small number of known structures, today, some form of structural information, either experimental or template-based models, is available for the majority of amino acids encoded by common model organism genomes. With the scientific focus of interest moving toward larger macromolecular complexes and dynamic networks of interactions, the integration of computational modeling methods with low-resolution experimental techniques allows the study of large and complex molecular machines. One of the open challenges for computational modeling and prediction techniques is to convey the underlying assumptions, as well as the expected accuracy and structural variability of a specific model, which is crucial to understanding its limitations. © 2013 Elsevier Ltd.

Frey Tirri B.,University of Basel
Current Problems in Dermatology | Year: 2011

Vaginally applied antimicrobial agents are widely used in the vagina in women with lower genital tract infections. An 'antimicrobial' is a general term that refers to a group of drugs that are effective against bacteria, fungi, viruses and protozoa. Topical treatments can be prescribed for a wide variety of vaginal infections. Many bacterial infections, such as bacterial vaginosis, desquamative inflammatory vaginitis or, as some European authors call it, aerobic vaginitis as well as infection with Staphylococcus aureus or group A streptococci, may be treated in this way. Candida vulvovaginitis is a fungal infection that is very amenable to topical treatment. The most common viral infections which can be treated with topical medications are condylomata acuminata and herpes simplex. The most often encountered protozoal vaginitis, which is caused by Trichomonas vaginalis, may be susceptible to topical medications, although this infection is treated systemically. This chapter covers the wide variety of commonly used topical antimicrobial agents for these diseases and focuses on the individual therapeutic agents and their clinical efficacy. In addition, potential difficulties that can occur in practice, as well as the usage of these medications in the special setting of pregnancy, are described in this chapter. © 2011 S. Karger AG, Basel.

Scharer L.,University of Basel
Current Biology | Year: 2014

Simultaneous hermaphrodites are both male and female, which could lead to conflicts between partners over optimal investment to the two sex functions. New evidence from hermaphroditic freshwater snails suggests that transferred seminal fluids affect the partner's male function. © 2014 Elsevier Ltd. All rights reserved.

Schatz G.,University of Basel
Biochemical and Biophysical Research Communications | Year: 2013

The question of how eukaryotic cells assemble their mitochondria was long considered to be inaccessible to biochemical investigation. This attitude changed about fifty years ago when the powerful tools of yeast genetics, electron microscopy and molecular biology were brought to bear on this problem. The rising interest in mitochondrial biogenesis thus paralleled and assisted in the birth of modern biology. This brief recollection recounts the days when research on mitochondrial biogenesis was an exotic effort limited to a small group of outsiders. © 2013 Elsevier Inc. All rights reserved.

Bolliger D.,University of Basel | Tanaka K.A.,University of Pittsburgh
Transfusion Medicine Reviews | Year: 2013

The value of thrombelastography (TEG) and thromboelastometry (ROTEM) to improve perioperative hemostasis is under debate. We aimed to assess the effects of TEG- or ROTEM-guided therapy in patients undergoing cardiac surgery on the use of allogeneic blood products. We analyzed 12 trials including 6835 patients, 749 of them included in 7 randomized controlled trials (RCTs). We collected data on the amount of transfused allogeneic blood products and on the proportion of patients who received allogeneic blood products or coagulation factor concentrates. Including all trials, the odds ratios (ORs) for transfusion of red blood cell (RBC) concentrates, fresh-frozen plasma (FFP), and platelets were 0.62 (95% confidence interval [CI], 0.56-0.69; P < .001), 0.28 (95% CI, 0.24-0.33; P < .001), and 0.55 (95% CI, 0.49-0.62; P < .001), respectively. However, more than 50% of the patients in this analysis were derived from one retrospective study. Including RCTs only, the ORs for transfusion of RBC, FFP, and platelets were 0.54 (95% CI, 0.38-0.77; P < .001), 0.36 (95% CI, 0.25-0.53; P < .001), and 0.57 (95% CI, 0.39-0.81; P = .002), respectively. The use of coagulation factor concentrates was reported in 6 studies, 2 of them were RCTs. The ORs for the infusion of fibrinogen and prothrombin complex concentrate were 1.56 (95% CI, 1.29-1.87; P < .001) and 1.74 (95% CI, 1.40-2.18; P < .001), respectively. However, frequencies and amounts were similar in the intervention and control group in the 2 RCTs. It is presumed that TEG- or ROTEM-guided hemostatic management reduces the proportion of patients undergoing cardiac surgery transfused with RBC, FFP, and platelets. This presumption is strongly supported by similar ORs found in the analysis including RCTs only. Patient blood management based on the transfusion triggers by TEG or ROTEM appears to be more restrictive than the one based on conventional laboratory testing. However, evidence for improved clinical outcome is limited at this time. © 2013 Elsevier Inc.

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.

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.

Pachur T.,University of Basel | Olsson H.,Max Planck Institute for Human Development
Cognitive Psychology | Year: 2012

In order to be adaptive, cognition requires knowledge about the statistical structure of the environment. We show that decision performance and the selection between cue-based and exemplar-based inference mechanisms can depend critically on how this knowledge is acquired. Two types of learning tasks are distinguished: learning by comparison, by which the decision maker learns which of two objects has a higher criterion value, and direct criterion learning, by which the decision maker learns an object's criterion value directly. In three experiments, participants were trained either with learning by comparison or with direct criterion learning and subsequently tested with paired-comparison, classification, and estimation tasks. Experiments 1 and 2 showed that although providing less information, learning by comparison led to better generalization (at test), both when generalizing to new objects and when the task format at test differed from the task format during training. Moreover, learning by comparison enabled participants to provide rather accurate continuous estimates. Computational modeling suggests that the advantage of learning by comparison is due to differences in strategy selection: whereas direct criterion learning fosters the reliance on exemplar processing, learning by comparison fosters cue-based mechanisms. The pattern in decision performance reversed when the task environment was changed from a linear (Experiments 1 and 2) to a nonlinear structure (Experiment 3), where direct criterion learning led to better decisions. Our results demonstrate the critical impact of learning conditions for the subsequent selection of decision strategies and highlight the key role of comparison processes in cognition. © 2012 Elsevier Inc.

Rothschild S.I.,University of Basel
Frontiers in Oncology | Year: 2013

Lung cancer is the leading cause of cancer deaths worldwide. microRNAs (miRNAs) are a class of small non-coding RNA species that have been implicated in the control of many fundamental cellular and physiological processes such as cellular differentiation, proliferation, apoptosis, and stem cell maintenance. Some miRNAs have been categorized as "oncomiRs" as opposed to "tumor suppressor miRs." This review focuses on the role of miRNAs in the lung cancer carcinogenesis and their potential as diagnostic, prognostic, or predictive markers. © 2013 Rothschild.

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.

Krumbholz M.,Ludwig Maximilians University of Munich | Derfuss T.,University of Basel | Hohlfeld R.,Ludwig Maximilians University of Munich | Meinl E.,Ludwig Maximilians University of Munich
Nature Reviews Neurology | Year: 2012

B cells and antibodies account for the most prominent immunodiagnostic feature in patients with multiple sclerosis (MS), namely oligoclonal bands. Furthermore, evidence is accumulating that B cells and antibodies contribute to MS pathogenesis in at least a subset of patients. The CNS provides a B-cell-fostering environment that includes B-cell trophic factors such as BAFF (B-cell-activating factor of the TNF family), APRIL (a proliferation-inducing ligand), and the plasma-cell survival factor CXCL12. Owing to this environment, the CNS of patients with MS is not only the target of the immunopathological process, but also becomes the site of local antibody production. B cells can increase or dampen CNS inflammation, but their proinflammatory effects seem to be more prominent in most patients, as B-cell depletion is a promising therapeutic strategy. Other therapies not primarily designed to target B cells have numerous effects on the B-cell compartment. This Review summarizes key features of B-cell biology, the role of B cells and antibodies in CNS inflammation, and current attempts to identify the targets of pathogenic antibodies in MS. We also review the effects of approved and investigational interventions - including CD20-depleting antibodies, BAFF/APRIL-depleting agents, alemtuzumab, natalizumab, FTY720, IFN-β, glatiramer acetate, steroids and plasma exchange - on B-cell immunology. © 2012 Macmillan Publishers Limited.

Wust G.,University of Basel
Nature Nanotechnology | Year: 2016

A huge effort is underway to develop semiconductor nanostructures as low-noise qubits. A key source of dephasing for an electron spin qubit in GaAs and in naturally occurring Si is the nuclear spin bath. The electron spin is coupled to each nuclear spin by the hyperfine interaction. The same interaction also couples two remote nuclear spins via a common coupling to the delocalized electron. It has been suggested that this interaction limits both electron and nuclear spin coherence, but experimental proof is lacking. We show that the nuclear spin decoherence time decreases by two orders of magnitude on occupying an empty quantum dot with a single electron, recovering to its original value for two electrons. In the case of one electron, agreement with a model calculation verifies the hypothesis of an electron-mediated nuclear spin–nuclear spin coupling. The results establish a framework to understand the main features of this complex interaction in semiconductor nanostructures. © 2016 Nature Publishing Group

Enderle L.,University of Basel | Enderle L.,Lunenfeld Tanenbaum Research Institute | McNeill H.,Lunenfeld Tanenbaum Research Institute | McNeill H.,University of Toronto
Science Signaling | Year: 2013

The Hippo pathway is a kinase cascade, formed by Hippo, Salvador, Warts, and Mats, that regulates the subcellular distribution and transcriptional activity of Yorkie. Yorkie is a transcriptional coactivator that promotes the expression of genes that inhibit apoptosis and drive cell proliferation. We review recent studies indicating that activity of the Hippo pathway is controlled by cell-cell junctions, cell adhesion molecules, scaffolding proteins, and cytoskeletal proteins, as well as by regulators of apical-basal polarity and extracellular tension.

Stieger B.,University of Zurich | Meier P.J.,University of Basel
Pharmacogenomics | Year: 2011

This article summarizes the impact of the pharmacogenetics of drug transporters expressed in the enterohepatic circulation on the pharmacokinetics and pharmacodynamics of drugs. The role of pharmacogenetics in the function of drug transporter proteins in vitro is now well established and evidence is rapidly accumulating from in vivo pharmacokinetic studies, which suggests that genetic variants of drug transporter proteins can translate into clinically relevant phenotypes. However, a large amount of conflicting information on the clinical relevance of drug transporter proteins has so far precluded the emergence of a clear picture regarding the role of drug transporter pharmacogenetics in medical practice. This is very well exemplified by the case of P-glycoprotein (MDR1, ABCB1). The challenge is now to develop pharmacogenetic models with sufficient predictive power to allow for translation into drug therapy. This will require a combination of pharmacogenetics of drug transporters, drug metabolism and pharmacodynamics of the respective drugs. © 2011 Future Medicine Ltd.

Cohen D.,University of Basel
Mathematics and Computers in Simulation | Year: 2012

In this article, we propose an approach, based on the variation-of- constants formula, for the numerical discretisation over long-time intervals of several stochastic oscillators. Additive and multiplicative noises are treated separately. The proposed schemes permit the use of large step sizes in the presence of a high frequency in the problem and offer various additional properties. These new numerical integrators can be viewed as a stochastic-generalisation of the trigonometric integrators for highly oscillatory deterministic problems. © 2012 IMACS. Published by Elsevier B.V. All rights reserved.

Bitzer J.,University of Basel
Gynecological Endocrinology | Year: 2012

Adolescence is a phase of life of utmost importance for the present and future physical, psychological, and social health of individuals of both genders. Contraception as a preventive measure and behavior has to be integrated into this developmental context. The aim hereby is not only the prevention of unwanted pregnancies, but also the maintenance and promotion of reproductive and sexual health in a broader sense. This includes protection against sexually transmitted diseases (STI), preservation of fertility, promotion of a self-determined and satisfying sexual life, diminution of general health risks and prevention of diseases which may occur later in life. The vaginal contraceptive ring seems to respond to most of these needs except for protection against STI. In conclusion, the vaginal ring is for these reasons an important option in the contraceptive care of adolescents. © 2012 Informa UK, Ltd.

Aging is associated with marked changes in the timing, consolidation and structure of sleep. Older people wake up frequently, get up earlier and have less slow wave sleep than young people, although the extent of these age-related changes differs considerably between individuals. Interindividual differences in homeostatic sleep regulation in young volunteers are associated with the variable-number, tandem-repeat (VNTR) polymorphism (rs57875989) in the coding region of the circadian clock gene PERIOD3 (PER3). However, predictors of these interindividual differences have yet to be identified in older people. Sleep electroencephalographic (EEG) characteristics and circadian rhythms were assessed in 26 healthy older volunteers (55-75 years) selected on the basis of homozygosity for either the long or short allele of the PER3 polymorphism. Homozygosity for the longer allele (PER3(5/5)) associated with a phase-advance in the circadian melatonin profile and an earlier occurrence of the melatonin peak within the sleep episode. Furthermore, older PER3(5/5) participants accumulated more nocturnal wakefulness, had increased EEG frontal delta activity (0.75-1.50 Hz), and decreased EEG frontal sigma activity (11-13 Hz) during non-rapid eye movement (REM) sleep compared with PER3(4/4) participants. Our results indicate that the polymorphism in the clock gene PER3 may contribute to interindividual differences in sleep and circadian physiology in older people. Copyright © 2012 Elsevier Inc. All rights reserved.

Odermatt A.,University of Basel
American Journal of Physiology - Renal Physiology | Year: 2011

The Western-style diet is characterized by its highly processed and refined foods and high contents of sugars, salt, and fat and protein from red meat. It has been recognized as the major contributor to metabolic disturbances and the development of obesity-related diseases including type 2 diabetes, hypertension, and cardiovascular disease. Also, the Western-style diet has been associated with an increased incidence of chronic kidney disease (CKD). A combination of dietary factors contributes to the impairment of renal vascularization, steatosis and inflammation, hypertension, and impaired renal hormonal regulation. This review addresses recent progress in the understanding of the association of the Western-style diet with the induction of dyslipidemia, oxidative stress, inflammation, and disturbances of corticosteroid regulation in the development of CKD. Future research needs to distinguish between acute and chronic effects of diets with high contents of sugars, salt, and fat and protein from red meat, and to uncover the contribution of each component. Improved therapeutic interventions should consider potentially altered drug metabolism and pharmacokinetics and be combined with lifestyle changes. A clinical assessment of the long-term risks of whole-body disturbances is strongly recommended to reduce metabolic complications and cardiovascular risk in kidney donors and patients with CKD. © 2011 the American Physiological Society.

Dieterle T.,University of Basel
Swiss Medical Weekly | Year: 2012

Arterial hypertension continues to represent the leading cause of morbidity and mortality world-wide. Diagnosis and therapy of arterial hypertension require adequate blood pressure measurements. Blood pressure is affected by constitutional and environmental factors as well as the measurement procedure itself, inducing substantial uncertainty with regard to adequate diagnosis and control of arterial hypertension. Therefore, current guidelines recommend that the diagnosis of arterial hypertension should not be solely based on conventional blood pressure measurements in the physician's office or in the hospital, but also on out-of-office ambulatory or home blood pressure measurements using clinically validated semi-automated or automated blood pressure measurement devices. Despite the enormous progress in the field of arterial hypertension, many aspects of blood pressure measurement require further intensive investigation, for example blood pressure measurement in special populations and distinct clinical situations, as well as the applicability and validation of novel measurement approaches and devices. This article provides an overview of current methods and trends in the field of non-invasive blood pressure measurement, an update on current clinical guidelines and an overview of blood pressure measurement in special populations.

Pena E.J.,Institute Of Biologie Moleculaire Des Plantes | Heinlein M.,Institute Of Biologie Moleculaire Des Plantes | Heinlein M.,University of Basel
Current Opinion in Plant Biology | Year: 2013

Anisotropic cell growth and the ability of plant cells to communicate within and across the borders of cellular and supracellular domains depends on the ability of the cells to dynamically establish polarized networks able to deliver structural and informational macromolecules to distinct cellular sites. Studies of organelle movements and transport of endogenous and viral proteins suggest that organelle and macromolecular trafficking pathways involve transient or stable interactions with cortical microtubule-associated endoplasmic reticulum sites (C-MERs). The observations suggest that C-MERs may function as cortical hubs that organize cargo exchange between organelles and allow the recruitment, assembly, and subsequently site-specific delivery of macromolecular complexes. We propose that viruses interact with such hubs for replication and intercellular spread. © 2013 Elsevier Ltd.

Leuppi J.D.,University of Basel
Current Opinion in Pulmonary Medicine | Year: 2014

PURPOSE OF REVIEW: This review describes different bronchoprovocation tests and their merits in diagnosing asthma. RECENT FINDINGS: A new indirect challenge test using dry powder mannitol has been made available and has been systematically validated and tested in different populations. SUMMARY: Airway hyperresponsiveness (AHR) is a characteristic feature of asthma, and its measurement using direct inhalation challenges, particularly with inhaled methacholine or histamine, or indirect challenges using stimuli such as exercise, dry air hyperpnea, distilled water, hypertonic saline and mannitol, and the pharmacological agent adenosine monophosphate is important in establishing a correct diagnosis. Direct challenge tests are sensitive and have a high negative predictive value to exclude asthma. This is particularly true in excluding asthma as a diagnosis in patients with symptoms that suggest asthma, but are caused by another condition. Indirect AHR correlates better with eosinophilic airway inflammation. Therefore, indirect challenge tests are seen as more specific. A newer indirect challenge test that uses a kit containing prepacked capsules of dry powder mannitol in different doses is safe and efficient to use. Indirect challenge tests are superior to direct challenge tests to confirm the presence of asthma. © 2013 Wolters Kluwer Health.

Gehring W.J.,University of Basel
Evolution and Development | Year: 2012

Developmental genetics of Drosophila continue to have a great impact on our understanding of evolution. The specification of the body plan involves four conceptual steps: 1) Localization of maternal mRNAs in the egg cytoplasm. 2) Translation of these RNAs and formation of morphogen gradients. 3) Subdivision of the antero-posterior gradient into a repetitive pattern of body segments. 4) Assignment of a specific identity to each segment by the Hox genes. The discovery of the Hox genes has uncovered a universal principle shared by all bilaterians; they serve as master control genes specifying organization along the antero-posterior axis. The ancestral arthropods presumably consisted of a series of more or less identical segments, which may be represented by recently discovered precambrian Lobopodia which have a pair of legs and a pair of eyes in each segment. The progressive divergence of Hox genes has led to progressive cephalization and caudalization. From the amino acid sequences of the clustered homeodomains we can deduce that the mesothoracic segment represents the prototype from the more anterior and the more posterior segments evolved. Pax6 has been identified as a master control gene for eye development in all bilaterians. Since Pax6 is involved in eye development in all bilaterian phyla, this argues strongly for a monophyletic origin of the metazoan eye. With the same tool box of transcription factors all the different eye-types can be constructed. © 2012 Wiley Periodicals, Inc.

Sauer E.,University of Basel
RNA Biology | Year: 2013

Over the past years, small non-coding RNAs (sRNAs) emerged as important modulators of gene expression in bacteria. Guided by partial sequence complementarity, these sRNAs interact with target mRNAs and eventually affect transcript stability and translation. The physiological function of sRNAs depends on the protein Hfq, which binds sRNAs in the cell and promotes the interaction with their mRNA targets. This important physiological function of Hfq as a central hub of sRNA-mediated regulation made it one of the most intensely studied proteins in bacteria. Recently, a new model for sRNA binding by Hfq has been proposed that involves the direct recognition of the sRNA 3′ end and interactions of the sRNA body with the lateral RNA-binding surface of Hfq. This review summarizes the current understanding of the RNA binding properties of Hfq and its (s)RNA complexes. Moreover, the implications of the new binding model for sRNA-mediated regulation are discussed. © 2013 Landes Bioscience.

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.

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.

Melchers F.,University of Basel | Planck M.,Max Planck Institute for Infection Biology
Annual Review of Immunology | Year: 2012

At the Centennial Exhibition of the Nobel Prize, the Nobel Foundation called it one of the ten cradles of creativity (1). The journal Nature likened its ideals to those of the French revolutionLiberté, Egalité, Fraternitéand called it a paradise (2) devoted to the science of immune systems: the Basel Institute for Immunology (BII). Founded by Roche in 1968, inaugurated in 1971, and closed in 2000, it was home to almost 450 scientific members, over 1,000 scientific visitors, and nearly 100 scientific advisors from more than 30 countries who worked in complete academic freedom and without commercial motives on over 3,500 projects, publishing more than 3,200 scientific papers, almost all of them on the structure and functions of immune systems of different species. This review contains a first collection of historical facts and dates that describe the background of the exceptionally successful performance and the strong scientific impact of the institute on the field of immunology. © 2012 by Annual Reviews. All rights reserved.

This review highlights an important novel aspect of the 2011 ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: the recommendations of a rapid rule-out protocol (0h and 3h) when high-sensitive cardiac troponin assays are available. The controversy relates to the scientific question how reliably patients can recall the onset or maximum of acute chest pain and the general question how conservative clinical practice guidelines should be. Several important arguments support the novel recommendations, particularly when accepting that guidelines should highlight treatment principles rather than individualised details. I hope that many physicians caring for patients with acute chest pain will actually take the time to read the new 2011 ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation. Certainly, application of the principles highlighted in there will help them in their daily clinical work.

Hopfera H.,University of Basel | Kemeny E.,University of Szeged
Current Opinion in Organ Transplantation | Year: 2013

Purpose of review: To provide an up-to-date overview about the assessment of donor biopsies and to discuss the current problems and chances of preimplantation biopsies for transplant allocation with a focus on the technical work up and the histological variables scored. Recent findings: Preimplantation biopsy results are the major reason for discarding procured extended donor criteria kidneys in the USA. There is neither a consensus on the work up, nor the reporting of preimplantation donor biopsies, nor the importance of the biopsy findings in the process of allocation. The best available data have been collected in the context of single vs. double kidney transplantation. A clinical risk factor score may help to define kidneys when a preimplantation biopsy is warranted. Punch biopsies using a skin punch device appear to be a reasonable alternative for surgeons fearing needle biopsies. Summary: Donor biopsies are very useful as zero-hour biopsies establishing baseline information for comparison with subsequent transplant biopsies. As none of the histological variables and scores provides perfect prediction, preimplantation biopsy results have to be interpreted in the context of all available donor and recipient information. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Jeger R.V.,University of Basel
Minerva Cardioangiologica | Year: 2012

Cardiogenic shock is a serious complication of acute myocardial infarction and occurs as a consequence of acute left ventricular failure and subsequent inappropriate tissue perfusion. While its incidence has been reported to be as high as 10% in the late 90ties, it has been steadily declining to currently less than 6% since the implementation of early revascularization as a class I indication in current guidelines. Despite recent advances in the treatment of cardiogenic shock, mortality is still high at approximately 50%. Current therapeutic approaches include early revascularization, fluid resuscitation, inotropic and vasopressor therapy, and mechanical circulatory support using intra-aortic balloon counterpulsation or percutaneous left ventricular assist devices. Novel treatment options such as specific inhibitors of inducible nitric oxide synthase or newer developments in mechanical circulatory support might be beneficial and should be tested in adequately powered randomized trials. However, difficulties in enrolling cardiogenic shock patients in randomized controlled trials are considerable. Until more data are available, cardiogenic shock patients should be treated aggressively with early revascularization and mechanical circulatory support to increase their probability of survival.

Nunnenkamp A.,University of Basel | Borkje K.,Yale University | Girvin S.M.,Yale University
Physical Review A - Atomic, Molecular, and Optical Physics | Year: 2012

In this Rapid Communication we discuss how red-sideband cooling is modified in the single-photon strong-coupling regime of cavity optomechanics where the radiation pressure of a single photon displaces the mechanical oscillator by more than its zero-point uncertainty. Using Fermi's golden rule we calculate the transition rates induced by the optical drive without linearizing the optomechanical interaction. In the resolved-sideband limit we find multiple-phonon cooling resonances for strong single-photon coupling that lead to nonthermal steady states including the possibility of phonon antibunching. Our study generalizes the standard linear cooling theory. © 2012 American Physical Society.

Schatz G.,University of Basel
Annual Review of Biochemistry | Year: 2012

This retrospective recounts the hunt for the mechanism of mitochondrial ATP synthesis, the early days of research on mitochondrial formation, and some of the colorful personalities dominating these often dramatic and emotional efforts. The narrative is set against the backdrop of postwar Austria and Germany and the stream of young scientists who had to leave their countries to receive postdoctoral training abroad. Many of them-including the author-chose the laboratory of a scientist their country had expelled a few decades before. The article concludes with some thoughts on the uniqueness of U.S. research universities and a brief account of the struggles to revive science in Europe. © 2012 by Annual Reviews. All rights reserved.

Podani J.,A.P.S. University | Schmera D.,University of Basel | Schmera D.,Balaton Limnological Research Institute
Oikos | Year: 2011

A conceptual framework is proposed to evaluate the relative importance of beta diversity, nestedness and agreement in species richness in presence - absence data matrices via partitioning pairwise gamma diversity into additive components. This is achieved by calculating three complementary indices that measure similarity, relative species replacement, and relative richness difference for all pairs of sites, and by displaying the results in a two-dimensional simplex diagram, or ternary plot. By summing two terms at a time, three one-dimensional simplices are derived correspondig to different contrasts: beta diversity versus similarity, species replacement versus nestedness and, finally, richness difference versus richness agreement. The simplex diagrams can be used to interpret underlying data structures by showing departure from randomness towards well-interpretable directions, as demonstrated by artificial and actual examples. In particular, one may appreciate how far data structure deviates from three extreme model situations: perfect nestedness, anti-nestedness and perfect gradient. Throughout the paper, we pay special attention to the measurement and interpetation of beta diversity and nestedness for pairs of sites, because these concepts have been in focus of ecological reseach for decades. The novel method can be used in community ecology, conservation biology, and biogeography, whenever the objective is to recover explanatory ecological processes behind patterns conveyed by presence-absence data. © 2011 The Authors.

Jaeger M.,University of Basel
European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society | Year: 2012

We report on a 61-year-old female patient who developed a spontaneous spinal epidural haematoma (SSEH) after being treated by rivaroxaban, a new agent for the prevention of venous thromboembolic events in orthopaedic surgery. Although the pathogenesis of SSEH is unclear, anticoagulant therapy is a known risk factor. The patient sustained a sudden onset of severe back pain in the thoracic spine, followed by paraplegia below T8, 2 days after proximal tibial osteotomy and rivaroxaban therapy. Magnetic resonance imaging (MRI) of the whole spine demonstrated a ventral SSEH from C2 to T8. Whilst preparing for the emergency evacuation of the SSEH, the neurological symptoms recovered spontaneously 4 h after onset without surgery. After monitored bed rest for 48 h the MRI was repeated and the SSEH was no longer present. This rare condition of spinal cord compression and unusually rapid spontaneous recovery has not previously been reported following rivaroxaban therapy.

Hasler C.C.,University of Basel
Journal of Children's Orthopaedics | Year: 2013

The history of surgical correction for adolescent idiopathic scoliosis reaches back about 100 years: the natural course of progressive, crippling and sometimes even life-threatening deformities which could not be controlled by external means called for effectual, invasive procedures. Hibbs 1911 aimed at halting progression by long, uninstrumented fusions. However, the lack of true correction, long rehabilitation times, high pseudarthrosis and infection rates, and a fusion mass which bent further once exposed to gravity again were not satisfying. The transition from slowing progression to halting progression and truly correcting the deformity lasted almost another half a century: Paul Harrington, confronted with many scoliotic polio patients, successfully introduced a hook-rod system for concave-distraction and convex-compression at the end of the 1950s. Many implant failures, a still-considerable pseudarthrosis rate, flattening of the sagittal profile and the lack of true three-dimensional (3D) correction were the shortcomings. In the 1970s the Frenchmen Cotrel and Dubousset took scoliosis surgery to the next level by introducing a versatile hook system and curve-pattern-adapted correction modes. The basics of the so-called derotation-manoeuvre consists in strategic distribution of the anchors along the curve, bending the rod accordingly, and rotating it back into the sagittal plane. The overall correction, stability and the fusion rates improved significantly. However, the effect on the sagittal and transverse plane were still limited. Lately, a better biomechanical understanding and bilateral, polysegmental strong three-column fixation with pedicle screw has become the benchmark method: in conjunction with posterior release techniques, osteotomies or even vertebral column resections for severe cases, it allows better 3D control (vertebral column manipulation), faster rehabilitation and better patient satisfaction. © 2012 EPOS.

Hefti F.,University of Basel
Journal of Children's Orthopaedics | Year: 2013

Adolescent idiopathic scoliosis is defined as a scoliosis that starts after the age of ten and has no clear underlying disease as a reason for its development. There is, however, a disparity between the growth of the vertebral bodies anteriorly and that of the posterior elements. The vertebral bodies grow faster than the posterior elements, resulting primarily in a lordosis. The diminished dorsal growth impedes the ventrally located vertebral bodies from increasing in height, forcing them to become distorted, i. e., rotate, in order to create space for themselves. This produces a rotational lordosis. The idea of looking at it in this way dates back to Somerville in 1952. Many recent studies have confirmed this idea and have shown that the spinal canal is shorter than the anterior ligament of the vertebral bodies. In a mathematical model of the spine it was demonstrated that-although the vertebral column in humans is still predominantly loaded in an axial direction-certain segments of the human spine (especially the backward inclined segments) are subject to dorsally directed shear loads as well. In addition to the antero-posterior difference in growth, there is also a deformation of the vertebral bodies itself in 3-D. This is probably secondary and not primary effects, but this question is still under discussion. For the treatment of scoliosis, the biomechanical principles of axial and transverse forces are used. The combination of axial and transverse loads is most beneficial for all curves. The axial forces provide most of the corrective bending moment when deformity is severe, while the transverse loads take over the correcting function when deformity is mild. The deformity angle of 53° is the break-even point for the axial and transverse loads. In more severe curves transverse forces become less and less efficient, while axial forces rapidly gain more and more effect. © 2013 EPOS.

Fathi A.-R.,Cantonal Hospital | Roelcke U.,Brain Tumor Center | 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.

Klinovaja J.,Harvard University | Yacoby A.,Harvard University | Loss D.,University of Basel
Physical Review B - Condensed Matter and Materials Physics | Year: 2014

We propose a scheme based on topological insulators to generate Kramers pairs of Majorana fermions or parafermions in the complete absence of magnetic fields. Our setup consists of two topological insulators whose edge states are brought close to an s-wave superconductor. The resulting proximity effect leads to an interplay between a nonlocal crossed Andreev pairing, which is dominant in the strong electron-electron interaction regime, and usual superconducting pairing, which is dominant at large separation between the two topological insulator edges. As a result, there are zero-energy bound states localized at interfaces between spatial regions dominated by the two different types of pairing. Due to the preserved time-reversal symmetry, the bound states come in Kramers pairs. If the topological insulators carry fractional edge states, the zero-energy bound states are parafermions, otherwise, they are Majorana fermions. © 2014 American Physical Society.

Betz M.J.,University of Basel | Enerback S.,Gothenburg University
Diabetes | Year: 2015

Brown adipose tissue (BAT) is a unique tissue that is able to convert chemical energy directly into heat when activated by the sympathetic nervous system. While initially believed to be of relevance only in human newborns and infants, research during recent years provided unequivocal evidence of active BAT in human adults. Moreover, it has become clear that BAT plays an important role in insulin sensitivity in rodents and humans. This has opened the possibility for exciting new therapies for obesity and diabetes. This review summarizes the current state of research with a special focus on recent advances regarding BAT and insulin resistance in human adults. Additionally, we provide an outlook on possible future therapeutic uses of BAT in the treatment of obesity and diabetes. © 2015 by the American Diabetes Association.

Arber W.,University of Basel
Genome Biology and Evolution | Year: 2011

The availability of spontaneously occurring genetic variants is an important driving force of biological evolution. Largely thanks to experimental investigations by microbial geneticists, we know today that several different molecular mechanisms contribute to the overall genetic variations. These mechanisms can be assigned to three natural strategies to generate genetic variants: 1) local sequence changes, 2) intragenomic reshuffling of DNA segments, and 3) acquisition of a segment of foreign DNA. In these processes, specific gene products are involved in cooperation with different nongenetic elements. Some genetic variations occur fully at random along the DNA filaments, others rather with a statistical reproducibility, although at many possible sites. We have to be aware that evolution in natural ecosystems is of higher complexity than under most laboratory conditions, not at least in view of symbiotic associations and the occurrence of horizontal gene transfer. The encountered contingency of genetic variation can possibly best ensure a long-term persistence of life under steadily changing living conditions. © The Author(s) 2010.

Kuss-Petermann M.,University of Gottingen | Wenger O.S.,University of Basel
Journal of Physical Chemistry Letters | Year: 2013

Proton-coupled electron transfer (PCET) with phenols has been investigated in considerable detail in recent years while at the same time analogous mechanistic studies of PCET with thiophenols have remained scarce. We report on PCET between a series of thiophenols and a photoexcited Ru(II) complex, which acts as a combined electron/proton acceptor. Depending on the exact nature of the thiophenol, PCET occurs through different reaction mechanisms. The results are discussed in the context of recent studies of PCET between phenols and photoexcited d6 metal complexes. © 2013 American Chemical Society.

Maurer V.,University of Basel
Computer Physics Communications | Year: 2016

T3PS is a program that can be used to quickly design and perform parameter scans while easily taking advantage of the multi-core architecture of current processors. It takes an easy to read and write parameter scan definition file format as input. Based on the parameter ranges and other options contained therein, it distributes the calculation of the parameter space over multiple processes and possibly computers. The derived data is saved in a plain text file format readable by most plotting software. The supported scanning strategies include: grid scan, random scan, Markov Chain Monte Carlo, numerical optimization. Several example parameter scans are shown and compared with results in the literature. © 2015 Elsevier B.V. All rights reserved.

Zimmerli W.,University of Basel | Sendi P.,University of Bern
Seminars in Immunopathology | Year: 2011

Implanted devices are mainly used to improve impaired function or to replace missing anatomic structures. They are made of synthetic material or devitalized biological structures. In contrast to vital transplants, they are not rejected by the body. However, the host reacts against these foreign bodies, a process which can be designated as biocompatibility. The interaction of the device with adjacent granulocytes and complement not only induces various degrees of inflammation but also impairs local microbial clearance. Foreign surfaces are a preferred target for bacterial adherence. While adhering bacteria are highly resistant to the bactericidal activity of phagocytes, they are also resistant to most antimicrobial agents. Certain bacteria may reside within host cells, and hence, evade host defense mechanisms by persisting intracellularly around implants. Nanotechnology minimizes clotting activation and bacterial adhesion by intravascular devices. Furthermore, surface coating with appropriate substances favorably influences biocompatibility as well as susceptibility to infection. In the future, "Microsystems Technology" deployed as intelligent device may decrease the risk of implant failure due to infection. © Springer-Verlag 2011.

Ebert D.,University of Basel
Science | Year: 2011

Gene duplication might explain the phenotypic adaptability of water fleas.

Development of acute graft-versus-host disease (aGVHD) predisposes to chronic GVHD with autoimmune manifestations. A characteristic of experimental aGVHD is the de novo generation of autoreactive T cells. Central tolerance is dependent on the intrathymic expression of tissue-restricted peripheral self-antigens (TRA), which is in mature medullary thymic epithelial cells (mTEC(high)) partly controlled by the autoimmune regulator (Aire). Because TECs are targets of donor T-cell alloimmunity, we tested whether murine aGVHD interfered with the capacity of recipient Aire(+)mTEC(high) to sustain TRA diversity. We report that aGVHD weakens the platform for central tolerance induction because individual TRAs are purged from the total repertoire secondary to a decline in the Aire(+)mTEC(high) cell pool. Peritransplant administration of an epithelial cytoprotective agent, fibroblast growth factor-7, maintained a stable pool of Aire(+)mTEC(high), with an improved TRA transcriptome despite aGVHD. Taken together, our data provide a mechanism for how autoimmunity may develop in the context of antecedent alloimmunity.

McLennan S.,University of Basel
Resuscitation | Year: 2012

Standard hospital CPR policies in many countries require CPR to be attempted on all patients having a cardiac arrest unless a Not-for-CPR order is in place. It has recently been shown that this approach is legally inappropriate in New Zealand. It appears that this argument may also potentially apply in other common law countries given the role that 'best interests' has in these jurisdictions in providing treatment to patients lacking decision-making capacity. Not-for-CPR orders provide an important and transparent mechanism for making advanced decisions regarding resuscitation. However, advanced planning is not always possible and it is legally inappropriate to require CPR to be performed when it is not in the patient's best interests. Notwithstanding the difficult practical balance that exists at the time of arrest between initiating CPR without delay or interruption for it to be effective for those whom CPR is in their best interests, and recognising as quickly as possible those patients for who CPR is not appropriate, it is argued that policies should be modified to allow clinicians to consider whether CPR is appropriate at time of arrest. Such a change may require ALS training to include a stronger emphasis on early recognition of patients for whom CPR is not in their best interests. © 2011 Elsevier Ireland Ltd.

Recurrences of diffuse large B-cell lymphomas (DLBCL) result in significant morbidity and mortality, but their underlying genetic and biological mechanisms are unclear. Clonal relationship in DLBCL relapses so far is mostly addressed by the investigation of immunoglobulin (IG) rearrangements, therefore, lacking deeper insights into genome-wide lymphoma evolution. We studied mutations and copy number aberrations in 20 paired relapsing and 20 non-relapsing DLBCL cases aiming to test the clonal relationship between primaries and relapses to track tumors’ genetic evolution and to investigate the genetic background of DLBCL recurrence. Three clonally unrelated DLBCL relapses were identified (15%). Also, two distinct patterns of genetic evolution in clonally related relapses were detected as follows: (1) early-divergent/branching evolution from a common progenitor in 6 patients (30%), and (2) late-divergent/linear progression of relapses in 11 patients (65%). Analysis of recurrent genetic events identified potential early drivers of lymphomagenesis (KMT2D, MYD88, CD79B and PIM1). The most frequent relapse-specific events were additional mutations in KMT2D and alterations of MEF2B. SOCS1 mutations were exclusive to non-relapsing DLBCL, whereas primaries of relapsing DLBCL more commonly displayed gains of 10p15.3–p12.1 containing the potential oncogenes PRKCQ, GATA3, MLLT10 and ABI1. Altogether, our study expands the knowledge on clonal relationship, genetic evolution and mutational basis of DLBCL relapses.Leukemia advance online publication, 14 June 2016; doi:10.1038/leu.2016.135. © 2016 Macmillan Publishers Limited

Klinovaja J.,Harvard University | Loss D.,University of Basel
Physical Review B - Condensed Matter and Materials Physics | Year: 2014

We propose a scheme to generate pairs of time-reversal invariant parafermions. Our setup consists of two quantum wires with Rashba spin-orbit interactions coupled to an s-wave superconductor, in the presence of electron-electron interactions. The zero-energy bound states localized at the wire ends arise from the interplay between two types of proximity-induced superconductivity: the usual intrawire superconductivity and the interwire superconductivity due to crossed Andreev reflections. If the latter dominates, which is the case for strong electron-electron interactions, the system supports Kramers pair of parafermions. Moreover, the scheme can be extended to a two-dimensional sea of time-reversal invariant parafermions. © 2014 American Physical Society.

Zocher M.,ETH Zurich | Zocher M.,University of Basel | Fung J.J.,Stanford University | Kobilka B.K.,Stanford University | Muller D.J.,ETH Zurich
Structure | Year: 2012

G protein-coupled receptors (GPCRs) are a class of versatile proteins that transduce signals across membranes. Extracellular stimuli induce inter- and intramolecular interactions that change the functional state of GPCRs and activate intracellular messenger molecules. How these interactions are established and how they modulate the functional state of GPCRs remain to be understood. We used dynamic single-molecule force spectroscopy to investigate how ligand binding modulates the energy landscape of the human β2 adrenergic receptor (β2AR). Five different ligands representing either agonists, inverse agonists or neutral antagonists established a complex network of interactions that tuned the kinetic, energetic, and mechanical properties of functionally important structural regions of β2AR. These interactions were specific to the efficacy profile of the ligands investigated and suggest that the functional modulation of GPCRs follows structurally well-defined interaction patterns. © 2012 Elsevier Ltd.

Oberbarnscheidt M.H.,University of Pittsburgh | Zecher D.,University of Basel | Lakkis F.G.,University of Pittsburgh
Seminars in Immunology | Year: 2011

The vertebrate innate immune system consists of inflammatory cells and soluble mediators that comprise the first line of defense against microbial infection and, importantly, trigger antigen-specific T and B cell responses that lead to lasting immunity. The molecular mechanisms responsible for microbial non-self recognition by the innate immune system have been elucidated for a large number of pathogens. How the innate immune system recognizes non-microbial non-self, such as organ transplants, is less clear. In this review, we approach this question by describing the principal mechanisms of non-self, or 'damaged' self, recognition by the innate immune system (pattern recognition receptors, the missing self theory, and the danger hypothesis) and discussing whether and how these mechanisms apply to allograft rejection. © 2011 Elsevier Ltd.

Comoglio F.,ETH Zurich | Paro R.,ETH Zurich | Paro R.,University of Basel
PLoS Computational Biology | Year: 2014

In metazoans, each cell type follows a characteristic, spatio-temporally regulated DNA replication program. Histone modifications (HMs) and chromatin binding proteins (CBPs) are fundamental for a faithful progression and completion of this process. However, no individual HM is strictly indispensable for origin function, suggesting that HMs may act combinatorially in analogy to the histone code hypothesis for transcriptional regulation. In contrast to gene expression however, the relationship between combinations of chromatin features and DNA replication timing has not yet been demonstrated. Here, by exploiting a comprehensive data collection consisting of 95 CBPs and HMs we investigated their combinatorial potential for the prediction of DNA replication timing in Drosophila using quantitative statistical models. We found that while combinations of CBPs exhibit moderate predictive power for replication timing, pairwise interactions between HMs lead to accurate predictions genome-wide that can be locally further improved by CBPs. Independent feature importance and model analyses led us to derive a simplified, biologically interpretable model of the relationship between chromatin landscape and replication timing reaching 80% of the full model accuracy using six model terms. Finally, we show that pairwise combinations of HMs are able to predict differential DNA replication timing across different cell types. All in all, our work provides support to the existence of combinatorial HM patterns for DNA replication and reveal cell-type independent key elements thereof, whose experimental investigation might contribute to elucidate the regulatory mode of this fundamental cellular process. © 2014 Comoglio, Paro.

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.

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.

Kuhne M.,University of Basel
Heart rhythm : the official journal of the Heart Rhythm Society | Year: 2013

The Achieve mapping catheter allows real-time recordings from the pulmonary veins (PVs) during cryoballoon (CB) ablation of atrial fibrillation (AF). To assess the clinical applicability of the Achieve mapping catheter and the value of real-time recordings from the PVs during CB. Patients with paroxysmal AF undergoing CB ablation were studied. Recordings from the PVs were analyzed during (real-time recordings) and after CB ablation and validated by using a variable circumferential mapping catheter (Achieve group; n = 20). A comparison was made by using a group of patients in whom CB ablation with a guidewire and a variable circumferential mapping catheter was performed (Guidewire group; n = 20). Forty patients (age 58±11 years; ejection fraction 0.59±0.07; left atrial size 40±6 mm) with paroxysmal AF were included. In the Achieve group, real-time recordings from the PVs could be obtained in 40 of 80 (50%) PVs and could be seen more often at the left-sided PVs (25 of 39, 64%) than at the right-sided PVs (15 of 41, 37%; P = .02). Validation with a standard circumferential mapping catheter confirmed PV isolation in 75 of 80 (93%) PVs. After a single procedure and a follow-up of 14±4 months, 25 of 40 (63%) patients were in sinus rhythm with no significant difference between groups. The Achieve catheter can be used as a substitute for a guidewire during CB ablation, but real-time recordings can be obtained only in half of the PVs and are not sufficient to accurately confirm isolation of all PVs. Copyright © 2013 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Affolter M.,University of Basel
Current Topics in Developmental Biology | Year: 2016

The field of "Developmental Biology" has dramatically changed over the past three decades. While genetic analysis had been center stage in the 1980s and continues to be a corner stone for investigations, the introduction of green fluorescent protein (GFP) in the 1990s has allowed us to look into living, developing embryos, and see how cells form tissues and how organ morphogenesis proceeds in real time. The introduction of protein binders into developmental studies some years ago has raised the precision yet another step, since it will allow the manipulation and study of how proteins function in real time. This chapter is a personal account on how GFP has, and how protein binders may, change the design of studies in the field of developmental biology. © 2016 Elsevier Inc.

Abdulle A.,Ecole Polytechnique Federale de Lausanne | Grote M.J.,University of Basel
Multiscale Modeling and Simulation | Year: 2011

A finite element heterogeneous multiscale method is proposed for the wave equation with highly oscillatory coefficients. It is based on a finite element discretization of an effective wave equation at the macro scale, whose a priori unknown effective coefficients are computed on sampling domains at the micro scale within each macro finite element. Hence the computational work involved is independent of the highly heterogeneous nature of the medium at the smallest scale. Optimal error estimates in the energy norm and the L 2 norm and convergence to the homogenized solution are proved, when both the macro and the micro scales are refined simultaneously. Numerical experiments corroborate the theoretical convergence rates and illustrate the behavior of the numerical method for periodic and heterogeneous media. © 2011 Society for Industrial and Applied Mathematics.

Tyndall A.,University of Basel
Hematology / the Education Program of the American Society of Hematology. American Society of Hematology. Education Program | Year: 2011

Over the past 15 years, more than 1500 patients have received HSCT, mostly autologous, as treatment for a severe autoimmune disease (AD). More than 1000 of these have been registered in the European Group for Bone Marrow Transplantation (EBMT) and European League Against Rheumatism (EULAR) combined database. A recent retrospective analysis of 900 patients showed that the majority had multiple sclerosis (MS; n = 345) followed by systemic sclerosis (SSc; n = 175), systemic lupus erythematosus (SLE; n = 85), rheumatoid arthritis (RA; n = 89), juvenile idiopathic arthritis (JIA; n = 65), and idiopathic cytopenic purpura (ITP; n = 37). An overall 85% 5-year survival and 43% progression-free survival was seen, with 100-day transplantation-related mortality (TRM) ranging between 1% (RA) and 11% (SLE and JIA). Approximately 30% of patients in all disease subgroups had a complete response, often durable despite full immune reconstitution. In many patients, such as in those with SSc, morphological improvement such as reduction of skin collagen and normalization of microvasculature was documented beyond any predicted known effects of intense immunosuppression alone. The high TRM was in part related to conditioning intensity, comorbidity, and age, but until the results of the 3 prospective randomized trials are known, an evidence-based modification of the conditioning regimen will not be possible.(1) In recent years, multipotent mesenchymal stromal cells (MSCs) have been tested in various AD, exploiting their immune-modulating properties and apparent low acute toxicity. Despite encouraging small phase 1/2 studies, no positive data from randomized, prospective studies are as yet available in the peer-reviewed literature.

Schatz G.,University of Basel
Nature Reviews Molecular Cell Biology | Year: 2014

Fifty years ago, academic science was a calling with few regulations or financial rewards. Today, it is a huge enterprise confronted by a plethora of bureaucratic and political controls. This change was not triggered by specific events or decisions but reflects the explosive 'knee' in the exponential growth that science has sustained during the past three-and-a-half centuries. Coming to terms with the demands and benefits of 'Big Science' is a major challenge for today's scientific generation. Since its foundation 50 years ago, the European Molecular Biology Organization (EMBO) has been of invaluable help in meeting this challenge. copyright © 2014 Macmillan Publishers Limited.

Morphological traits typically scale with the overall body size of an organism. A meaningful comparison of trait values among individuals or populations that differ in size therefore requires size correction. A frequently applied size correction method involves subjecting the set of n morphological traits of interest to (common) principal component analysis [(C)PCA], and treating the first principal component [(C)PC1] as a latent size variable. The remaining variation (PC2-PCn) is considered size-independent and interpreted biologically. I here analyze simulated data and natural datasets to demonstrate that this (C)PCA-based size correction generates systematic statistical artifacts. Artifacts arise even when all traits are tightly correlated with overall size, and they are particularly strong when the magnitude of variance is heterogeneous among the traits, and when the traits under study are few. (C)PCA-based approaches are therefore inappropriate for size correction and should be abandoned in favor of methods using univariate general linear models with an adequate independent body size metric as covariate. As I demonstrate, (C)PC1 extracted from a subset of traits, not themselves subjected to size correction, can provide such a size metric. © 2011 Springer-Verlag.

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.

De Geyter C.,University of Basel
Swiss Medical Weekly | Year: 2012

Since the first introduction of hormonal contraception, family planning and procreation have become increasingly medicalised. The rapid spread of assisted reproductive technology (ART) is part of this natural development of modern society. However, in Switzerland it has caused severe controversy and its use has been framed by a restrictive legislation since 2001. Despite this, the yearly number of reported treatments with in-vitro fertilisation (IVF), with intracytoplasmic sperm injection (ICSI) and with transfer of frozen/thawed oocytes in the pronucleate stage has risen to more than 10,000 in 2011. As over time the protocols for ovarian stimulation have reached higher levels of efficacy and as the composition of the culture media used for embryo development in the laboratory has become more elaborate, the implantation rate of the transferred embryos has steadily improved leading to higher pregnancy rates, but also resulting in a higher risk of multiple delivery. Deliveries of multiples, including those with twins, often occur prematurely causing significant maternal and neonatal morbidity and mortality. Improved assessment of the developmental potential of embryos together with better freezing protocols have lead to the selection and transfer of one single embryo per treatment cycle in an increasing number of countries but not in Switzerland. This strategy has been shown to be very effective in preventing multiple deliveries without compromising the overall pregnancy rates. In addition, well accepted treatment modalities in assisted reproduction, such as embryo cryopreservation, oocyte donation and preimplantation genetic diagnosis have not been implemented in Switzerland due to the current restrictive legislation. The still present ban on cryopreservation of embryos in Switzerland now leads to a higher incidence of complications and neonatal death than necessary in the presence of an adapted legal environment. There is an urgent need for a public debate about the future role of modern reproductive medicine in Swiss society. This discussion should focus not only on the risks of ART but also on its opportunities.

Wymann M.P.,University of Basel | Solinas G.,University of Fribourg
Annals of the New York Academy of Sciences | Year: 2013

Phosphoinositide 3-kinase γ (PI3Kγ) plays a central role in inflammation, allergy, cardiovascular, and metabolic disease. Obesity is accompanied by chronic, low-grade inflammation. As PI3Kγ plays a major role in leukocyte recruitment, targeting of PI3Kγ has been considered to be a strategy for attenuating progression of obesity to insulin resistance and type 2 diabetes. Indeed, PI3Kγ null mice are protected from high fat diet-induced obesity, metabolic inflammation, fatty liver, and insulin resistance. The lean phenotype of the PI3Kγ-null mice has been linked to increased thermogenesis and energy expenditure. Surprisingly, the increase in fat mass and metabolic aberrations were not linked to PI3Kγ activity in the hematopoietic compartment. Thermogenesis and oxygen consumption are modulated by PI3Kγ lipid kinase-dependent and -independent signaling mechanisms. PI3Kγ signaling controls metabolic and inflammatory stress, and may provide an entry point for therapeutic strategies in metabolic disease, inflammation, and cardiovascular disease. © 2013 New York Academy of Sciences.

Zack L.N.,University of Arizona | Zack L.N.,University of Basel | Ziurys L.M.,University of Arizona
Astrophysical Journal | Year: 2013

Observations of CO, HCO+, and H2CO have been carried out at nine positions across the Helix Nebula (NGC 7293) using the Submillimeter Telescope and the 12 m antenna of the Arizona Radio Observatory. Measurements of the J = 1 → 0, 2 → 1, and 3 →2 transitions of CO, two transitions of HCO+ (J = 1 → 0 and 3 →2), and five lines of H2CO (J Ka, Kc = 10, 1 → 0 0, 0, 21, 2 → 11, 1,