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Pasini D.,Italian National Cancer Institute | Di Croce L.,The Barcelona Institute of Science and Technology | Di Croce L.,University Pompeu Fabra | Di Croce L.,Catalan Institution for Research and Advanced Studies
Current Opinion in Genetics and Development | Year: 2016

The activities of the heterogeneous Polycomb (PcG) group of proteins ensure that the developmental processes of proliferation and cellular identity establishment are carried out correctly. PcG proteins assemble stable multiprotein complexes that, together with additional factors, maintain their target genes in a transcriptionally repressive state. The biochemical and functional features of PcG proteins have been extensively investigated over the years. Here we analyse the biochemical and mechanistic proprieties of PcG proteins with respect to recent advances that link the genetic alterations of PcG activity to cancer development. © 2016 Elsevier Ltd.


News Article | December 8, 2016
Site: www.eurekalert.org

Bacterial resistance does not come just through adaptation to antibiotics, sometimes the bacteria simply go to sleep. An international team of researchers is looking at compounds that attack bacteria's ability to go dormant and have found the first oxygen-sensitive toxin antitoxin system. "Antibiotics can only kill bacteria when they are actively growing and dividing," said Thomas K. Wood, professor of chemical engineering and holder of the Biotechnology Endowed Chair, Penn State. "But, environmental stress factors often turn on a bacterial mechanism that creates a toxin that makes the cell dormant and therefore antibiotic resistant." Bacteria that form biofilms are often difficult to kill. They can react to environmental signals and produce a toxin that makes the cells go dormant. Antibiotics cannot target dormant cells. One type of bacterium that does this lives in the gastrointestinal track. Bile, secreted by the liver and stored in the gall bladder, when released into the GI track can kill bacteria. In the presence of bile, these bacteria produce a protein that is a self-toxin and the bacteria go dormant. When the bile is gone, the bacteria produce another protein that destroys the inhibitor protein and the bacteria come alive. These toxin antitoxin systems are inherent in bacteria and serve to protect them against a variety of external, environmental insults. Wood and his colleagues characterized the first toxin antitoxin system in a biofilm. They report today (Dec. 8) in Nature Communications that this system also is the first known to be oxygen-dependent. The characterization was done at the molecular and atomic level by researchers at the Biomolecular NMR Laboratory at the University of Barcelona, Spain. They found that the E. coli antitoxin's structure had channels that are just large enough for oxygen to pass through. The toxin in this system is Hha and the antitoxin is TomB. However, unlike other toxin antitoxin pairs where the toxin makes the cell dormant and the antitoxin inactivates the toxin by binding, this system needs oxygen in the presence of the antitoxin to oxidize the toxin and wake up the bacteria. "If we understand the toxin antitoxin systems at a molecular or atomic level, we can make better antimicrobials," said Wood. "I would argue that the toxin antitoxin systems are fundamental to the physiology of all bacteria. We hope this will give us insight into how they survive the antibiotics." Free-swimming bacteria are usually easily targeted by antibodies or antibiotics, but bacteria that form biofilms are harder to kill. In tuberculosis, the bacteria have as many as 88 different toxin options to react to environmental stresses. According to Wood, this is one of the reasons that TB patients need to stay on antibiotics for months or years to clear the body of all the bacteria. Biofilms are involved in 80 percent of human infections and are one of the strongest contributors to the pressing antibiotic resistance problem. The researchers found that 10 percent oxygen is sufficient to wake up the bacteria, but in a biofilm, the problem becomes accessibility. The bacteria on the edges of the film can be easily exposed to oxygen, but those further inside the film might not come into contact with the oxygen. The channels that form in the E. coli biofilm allow the oxygen to penetrate into the biofilm, awaken the bacteria, break up the biofilm and disperse it. The researchers suggest that this type of toxin, one that is oxygen-dependent, could become the target for antibacterial treatments to inhibit the formation of biofilms. Also working on this project at Penn State were W.C. Soo, postdoctoral fellow, and Thammajun L. Wood, research associate in chemical engineering. Other researchers included Oriol Marimon, Joáo M.C. Teixeira, Tiago N. Cordeiro, Irene Amata, Jesús Garcia, Ainara Morera and Miquel Pons, all at Biomolecular NMR Laboratory, Inorganic and Organic Chemistry Department, University of Barcelona, Spain; Maxim Mayzel, and Vladislave Yu. Orekhov, Swedish NMR Centre, Gothenburg University, Gothenburg, Sweden; and Marina Gay and Marta Vilaseca, Institute for Research in Biomedicine, The Barcelona Institute of Science and Technology, Barcelona, Spain.


News Article | December 19, 2016
Site: www.eurekalert.org

Transparent conductors are one of the key elements of today's electronic and optoelectronic devices such as displays, light emitting diodes, photovoltaic cells, smart phones, etc. Most of the current technology is based on the use of the semiconductor Indium Tin Oxide (ITO) as a transparent conducting material. However, even though ITO presents several exceptional properties, such as a large transmission and low resistance, it still lacks mechanical flexibility, needs to be processed under high temperatures and is expensive to produce. An intensive effort has been devoted to the search of alternative TC materials that could definitively replace ITO, especially in the search for device flexibility. While the scientific community has investigated materials such as Al-doped ZnO (AZO), carbon nanotubes, metal nanowires, ultrathin metals, conducting polymers and most recently graphene, none of these have been able to present optimal properties that would make them the candidate to replace ITO. Today ultrathin metal films (UTMFs) have been shown to present very low resistance although their transmission is also low unless antireflection (AR) undercoat and overcoat layers are added to the structure. ICFO researchers Rinu Abraham Maniyara, Vahagn K. Mkhitaryan, Tong Lai Chen, and Dhriti Sundar Ghosh, led by ICREA Prof at ICFO Valerio Pruneri, have developed a room temperature processed multilayer transparent conductor optimizing the antireflection properties to obtain high optical transmissions and low losses, with large mechanical flexibility properties. They have published their results in a recent paper published in Nature Communications. In their study, ICFO researchers applied an Al doped ZnO overcoat and a TiO2 undercoat layer with precise thicknesses to a highly conductive Ag ultrathin film. By using destructive interference, the researchers showed that the proposed multilayer structure could lead to an optical loss of approximately 1.6% and an optical transmission greater than 98% in the visible. As Prof. Valerio Pruneri states, "we have used a simple design to achieve a transparent conductor with the highest performance to date and at the same time other outstanding attributes required for relevant applications in industry". This result represents a record fourfold improvement in figure of merit over ITO and also presents superior mechanical flexibility in comparison to this material. The results of this study show the potential that this multilayer structure could have in future technologies that aim at more efficient and flexible electronic and optoelectronic devices. ICFO - The Institute of Photonic Sciences, member of The Barcelona Institute of Science and Technology, is a research center located in a specially designed, 14.000 m2-building situated in the Mediterranean Technology Park in the metropolitan area of Barcelona. It currently hosts 400 people, including research group leaders, post-doctoral researchers, PhD students, research engineers, and staff. ICFOnians are organized in 23 research groups working in 60 state-of-the-art research laboratories, equipped with the latest experimental facilities and supported by a range of cutting-edge facilities for nanofabrication, characterization, imaging and engineering. The Severo Ochoa distinction awarded by the Ministry of Science and Innovation, as well as 14 ICREA Professorships, 22 European Research Council grants and 6 Fundació Cellex Barcelona Nest Fellowships, demonstrate the centre's dedication to research excellence, as does the institute's consistent appearance in top worldwide positions in international rankings. From an industrial standpoint, ICFO participates actively in the European Technological Platform Photonics21 and is also very proactive in fostering entrepreneurial activities and spin-off creation. The center participates in incubator activities and seeks to attract venture capital investment. ICFO hosts an active Corporate Liaison Program that aims at creating collaborations and links between industry and ICFO researchers. To date, ICFO has created 5 successful start-up companies.


News Article | October 25, 2016
Site: www.nanotech-now.com

Home > Press > Physicists use lasers to capture first snapshots of rapid chemical bonds breaking Abstract: Lasers have successfully recorded a chemical reaction that happens as fast as a quadrillionth of a second, which could help scientists understand and control chemical reactions. The idea for using a laser to record a few femtoseconds of a molecule's extremely fast vibrations as it breaks apart came from Kansas State University physicists. Chii-Dong Lin, university distinguished professor of physics, and Anh-Thu Le, research associate professor in James R. Macdonald Laboratory, are part of an international collaborative project published in the Oct. 21 issue of Science. "If you want to see something that happens very, very fast, you need a tool that can measure a very, very tiny time period," Lin said. "The only light available in femtosecond measurements is a laser." A femtosecond is one-millionth of a billionth of a second, which is a million times shorter than a nanosecond. Until recently, there was no way to measure what happens during a chemical reaction in that short of a period. Lin's research group made its first molecular movie of an oxygen molecule using lasers in 2012, but to record a larger molecule -- such as the four-atom acetylene molecule -- they needed a more advanced laser. After five years of collaboration with Jens Biegert's group from ICFO-The Institute of Photonic Sciences, a member of The Barcelona Institute of Science and Technology, Lin's idea became reality. The international team used the molecule's own electrons to scatter the molecule -- a process called mid-infrared laser-induced electron diffraction, or LIED -- and capture snapshots of acetylene as it is breaking apart. An intense laser is used to affectan acetylene molecule -- composed of two hydrogen atoms and two carbon atoms -- to strip out an electron and initiate the breakup of the molecule. After nine femtoseconds, the laser drives the free electron back to the elongated molecule to create an image. "Scientists will eventually be able to apply this tool in chemistry, biology and other physical sciences to look at different types of molecules and processes," Lin said. According to Lin, acetylene's four-atom chemical structure provides multiple possibilities where the bonds could break. Being able to measure where and when those breaks occur can help researchers better understand chemical reactions, which Lin said will lead to better control of a reaction and is applicable to multiple areas of science. "In order to control something, you have to know where it is first," Lin said. "If you throw a ball over a house, you can't see what happens to it, so you can't control it anymore. But if you have a way to see each second of the ball in the air, you can figure out why it ends up where it does and potentially change the way you throw it to control the outcome or to influence it in real time." Lin's research group started working with Kansas State University distinguished professor emeritus Lew Cocke's research group in 2008 to conduct the first LIED experiment, which led to the current development. The initial experiments enabled the researchers to apply their theory to decode signals from electrons that produce the image. By decoding the image, the researchers accurately measured the molecule's new bond distances, which are smaller than one hundred-millionth of a centimeter. "Since the snapshots, which are taken by the electrons, occur in a very strong laser field, it was thought to be nearly impossible to decode the electron information and measure the small distances," said Le, who provided critical decoding of the molecule's structure in the snapshot from Barcelona. "This is the first real-time observation of the breakup of a molecule within nine femtoseconds." ### The international collaborators are from the ICFO-The Institute of Photonic Sciences, The Barcelona Institute of Science and Technology, and Catalan Institution for Research and Advanced Studies, all in Spain; the Leiden University in The Netherlands; The University of Kassel, the Center for Free-Electron Laser Science, Max Planck Institute for Nuclear Physics, Physikalisch-Technische Bundesanstalt and University of Jena, all in Germany; and Aarhus University in Denmark. For more information, please click If you have a comment, please us. Issuers of news releases, not 7th Wave, Inc. or Nanotechnology Now, are solely responsible for the accuracy of the content.


Pegueroles C.,The Barcelona Institute of Science and Technology | Pegueroles C.,University Pompeu Fabra | Gabaldon T.,The Barcelona Institute of Science and Technology | Gabaldon T.,University Pompeu Fabra | Gabaldon T.,Catalan Institution for Research and Advanced Studies
BMC Biology | Year: 2016

Background: Metazoans transcribe many long non-coding RNAs (lncRNAs) that are poorly conserved and whose function remains unknown. This has raised the questions of what fraction of the predicted lncRNAs is actually functional, and whether selection can effectively constrain lncRNAs in species with small effective population sizes such as human populations. Results: Here we evaluate signatures of selection in human lncRNAs using inter-specific data and intra-specific comparisons from five major populations, as well as by assessing relationships between sequence variation and predictions of secondary structure. In all analyses we included a reference of functionally characterized lncRNAs. Altogether, our results show compelling evidence of recent purifying selection acting on both characterized and predicted lncRNAs. We found that RNA secondary structure constrains sequence variation in lncRNAs, so that polymorphisms are depleted in paired regions with low accessibility and tend to be neutral with respect to structural stability. Conclusions: Important implications of our results are that secondary structure plays a role in the functionality of lncRNAs, and that the set of predicted lncRNAs contains a large fraction of functional ones that may play key roles that remain to be discovered. © 2016 Pegueroles and Gabaldon.


Bartesaghi R.,University of Bologna | Haydar T.F.,Boston University | Delabar J.M.,University Paris Diderot | Dierssen M.,The Barcelona Institute of Science and Technology | And 3 more authors.
Journal of Neuroscience | Year: 2015

Down syndrome (DS) is a relatively common genetic condition caused by the triplication of human chromosome 21. No therapies currently exist for the rescue of neurocognitive impairment in DS. This review presents exciting findings showing that it is possible to restore brain development and cognitive performance in mouse models of DS with therapies that can also apply to humans. This knowledge provides a potential breakthrough for the prevention of intellectual disability in DS. © 2015 the authors.


Papasaikas P.,The Barcelona Institute of Science and Technology | Papasaikas P.,University Pompeu Fabra | Valcarcel J.,The Barcelona Institute of Science and Technology | Valcarcel J.,University Pompeu Fabra | Valcarcel J.,Catalan Institution for Research and Advanced Studies
Trends in Biochemical Sciences | Year: 2016

The spliceosome, one of the most complex machineries of eukaryotic cells, removes intronic sequences from primary transcripts to generate functional messenger and long noncoding RNAs (lncRNA). Genetic, biochemical, and structural data reveal that the spliceosome is an RNA-based enzyme. Striking mechanistic and structural similarities strongly argue that pre-mRNA introns originated from self-catalytic group II ribozymes. However, in the spliceosome, protein components organize and activate the catalytic-site RNAs, and recognize and pair together splice sites at intron boundaries. The spliceosome is a dynamic, reversible, and flexible machine that chaperones small nuclear (sn) RNAs and a variety of pre-mRNA sequences into conformations that enable intron removal. This malleability likely contributes to the regulation of alternative splicing, a prevalent process contributing to cell differentiation, homeostasis, and disease. The spliceosome is a ribonucleoprotein complex that chaperones pre-mRNA and small nuclear (sn)RNAs into conformations resembling the RNA-based catalytic core of group II introns. Proteins such as pre-mRNA-processing-splicing factor 8 (Prp8) organize and regulate the activation of the RNA-based catalytic core of the spliceosome. The catalytic site is open to accommodate different intron lengths and sequences, and to interact with other cellular machineries. Spliceosomal subcomplexes recognize and pair splice-site sequences in a highly dynamic and reversible fashion. This architecture, together with iterative substrate recognition and proofreading, provide opportunities for alternative splicing regulation. © 2015 Elsevier Ltd.


Mas G.,The Barcelona Institute of Science and Technology | Mas G.,University Pompeu Fabra | Di Croce L.,The Barcelona Institute of Science and Technology | Di Croce L.,University Pompeu Fabra | Di Croce L.,Catalan Institution for Research and Advanced Studies
Current Opinion in Cell Biology | Year: 2016

Polycomb-group proteins maintain embryonic stem cell identity by repressing genes that encode for developmental regulatory factors. Failure to properly control developmental transcription programs by Polycomb proteins is linked to disease and embryonic lethality. Recent technological advances have revealed that developmentally repressed genes tend to cluster in the three-dimensional space of the nucleus. Importantly, spatial clustering of developmental genes is fundamental for the correct regulation of gene expression during early development. Here, we outline novel insights and perspectives regarding the function of Polycomb complexes in shaping the stem cell genome architecture, and discuss how this function might be required to properly orchestrate transcriptional programs during differentiation. © 2016 Elsevier Ltd


Davies A.,University of Edinburgh | Louis M.,The Barcelona Institute of Science and Technology | Louis M.,University Pompeu Fabra | Webb B.,University of Edinburgh
PLoS Computational Biology | Year: 2015

Detailed observations of larval Drosophila chemotaxis have characterised the relationship between the odour gradient and the runs, head casts and turns made by the animal. We use a computational model to test whether hypothesised sensorimotor control mechanisms are sufficient to account for larval behaviour. The model combines three mechanisms based on simple transformations of the recent history of odour intensity at the head location. The first is an increased probability of terminating runs in response to gradually decreasing concentration, the second an increased probability of terminating head casts in response to rapidly increasing concentration, and the third a biasing of run directions up concentration gradients through modulation of small head casts. We show that this model can be tuned to produce behavioural statistics comparable to those reported for the larva, and that this tuning results in similar chemotaxis performance to the larva. We demonstrate that each mechanism can enable odour approach but the combination of mechanisms is most effective, and investigate how these low-level control mechanisms relate to behavioural measures such as the preference indices used to investigate larval learning behaviour in group assays. © 2015 Davies et al.


PubMed | University of Western Brittany and the Barcelona Institute of Science and Technology
Type: Journal Article | Journal: Medecine sciences : M/S | Year: 2017

Pre-mRNA splicing is an obligatory step required to assemble the vast majority of mRNAs in eukaryotes. In humans, each gene gives rise to at least two transcripts, with an average 6-8 spliced transcripts per gene. Pre-mRNA splicing is not unequivocal. Variations may occur, such that splicing can become alternative, thereby participating in increasing protein variability and restricting the gap that exists between the relatively low number of genes - between 20,000 and 25,000 in humans - and the much higher number of distinct proteins - at least 100,000. In addition, although alternative pre-mRNA splicing often fulfils cell-specific needs, many aberrant splicing events can happen and lead to either hereditary or acquired diseases such as neurodegenerative diseases or cancers. In those cases, alternative splicing events may serve as disease-associated markers, or even as targets for corrective approaches. In this review, we will summarize the main aspects of regulated alternative splicing. We will present the spliceosome, a large ribonucleoprotein complex that orchestrates the splicing reactions and that was recently identified as a preferential target for mutations in several pathologies. We shall discuss some spliceosome-associated defects linked to either cis (i.e on the DNA) or trans (e.g. in proteins) alterations of splicing machinery, like those that have been reported in genetic or acquired diseases.

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