Showing papers by "University of Geneva published in 2015"
TL;DR: The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations, and has reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole-generation sequencing, deep exome sequencing, and dense microarray genotyping.
Abstract: The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations. Here we report completion of the project, having reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole-genome sequencing, deep exome sequencing, and dense microarray genotyping. We characterized a broad spectrum of genetic variation, in total over 88 million variants (84.7 million single nucleotide polymorphisms (SNPs), 3.6 million short insertions/deletions (indels), and 60,000 structural variants), all phased onto high-quality haplotypes. This resource includes >99% of SNP variants with a frequency of >1% for a variety of ancestries. We describe the distribution of genetic variation across the global sample, and discuss the implications for common disease studies.
12,661 citations
University of Cambridge1, Istituto Italiano di Tecnologia2, Lancaster University3, University of Manchester4, Catalan Institution for Research and Advanced Studies5, Technical University of Denmark6, Nokia7, Queen Mary University of London8, University of Trento9, fondazione bruno kessler10, Technische Universität München11, Polytechnic University of Milan12, Centre national de la recherche scientifique13, University of Trieste14, University of Ioannina15, University of Geneva16, Trinity College, Dublin17, Texas Instruments18, University of Paris19, Spanish National Research Council20, Leiden University21, Delft University of Technology22, University of Patras23, École Normale Supérieure24, Radboud University Nijmegen25, Nest Labs26, Airbus UK27, Seoul National University28, Yonsei University29, University of Oxford30, Chalmers University of Technology31, University of Groningen32, STMicroelectronics33, Chemnitz University of Technology34, Max Planck Society35, Aalto University36
TL;DR: An overview of the key aspects of graphene and related materials, ranging from fundamental research challenges to a variety of applications in a large number of sectors, highlighting the steps necessary to take GRMs from a state of raw potential to a point where they might revolutionize multiple industries are provided.
Abstract: We present the science and technology roadmap for graphene, related two-dimensional crystals, and hybrid systems, targeting an evolution in technology, that might lead to impacts and benefits reaching into most areas of society. This roadmap was developed within the framework of the European Graphene Flagship and outlines the main targets and research areas as best understood at the start of this ambitious project. We provide an overview of the key aspects of graphene and related materials (GRMs), ranging from fundamental research challenges to a variety of applications in a large number of sectors, highlighting the steps necessary to take GRMs from a state of raw potential to a point where they might revolutionize multiple industries. We also define an extensive list of acronyms in an effort to standardize the nomenclature in this emerging field.
2,560 citations
TL;DR: A measurement of the Higgs boson mass is presented based on the combined data samples of the ATLAS and CMS experiments at the CERN LHC in the H→γγ and H→ZZ→4ℓ decay channels.
Abstract: A measurement of the Higgs boson mass is presented based on the combined data samples of the ATLAS and CMS experiments at the CERN LHC in the H→γγ and H→ZZ→4l decay channels. The results are obtained from a simultaneous fit to the reconstructed invariant mass peaks in the two channels and for the two experiments. The measured masses from the individual channels and the two experiments are found to be consistent among themselves. The combined measured mass of the Higgs boson is mH=125.09±0.21 (stat)±0.11 (syst) GeV.
1,567 citations
TL;DR: Strong evidence for dust and no statistically significant evidence for tensor modes is found and various model variations and extensions are probe, including adding a synchrotron component in combination with lower frequency data, and find that these make little difference to the r constraint.
Abstract: We report the results of a joint analysis of data from BICEP2/Keck Array and Planck. BICEP2 and Keck Array have observed the same approximately 400 deg2 patch of sky centered on RA 0h, Dec. −57.5deg. The combined maps reach a depth of 57 nK deg in Stokes Q and U in a band centered at 150 GHz. Planck has observed the full sky in polarization at seven frequencies from 30 to 353 GHz, but much less deeply in any given region (1.2 μK deg in Q and U at 143 GHz). We detect 150×353 cross-correlation in B-modes at high significance. We fit the single- and cross-frequency power spectra at frequencies above 150 GHz to a lensed-ΛCDM model that includes dust and a possible contribution from inflationary gravitational waves (as parameterized by the tensor-to-scalar ratio r). We probe various model variations and extensions, including adding a synchrotron component in combination with lower frequency data, and find that these make little difference to the r constraint. Finally we present an alternative analysis which is similar to a map-based cleaning of the dust contribution, and show that this gives similar constraints. The final result is expressed as a likelihood curve for r, and yields an upper limit r0.05<0.12 at 95% confidence. Marginalizing over dust and r, lensing B-modes are detected at 7.0σ significance.
1,255 citations
TL;DR: Tissues exhibit characteristic transcriptional signatures that show stability in postmortem samples that are dominated by a relatively small number of genes, though few are exclusive to a particular tissue and vary more across tissues than individuals.
Abstract: Transcriptional regulation and posttranscriptional processing underlie many cellular and organismal phenotypes. We used RNA sequence data generated by Genotype-Tissue Expression (GTEx) project to investigate the patterns of transcriptome variation across individuals and tissues. Tissues exhibit characteristic transcriptional signatures that show stability in postmortem samples. These signatures are dominated by a relatively small number of genes—which is most clearly seen in blood—though few are exclusive to a particular tissue and vary more across tissues than individuals. Genes exhibiting high interindividual expression variation include disease candidates associated with sex, ethnicity, and age. Primary transcription is the major driver of cellular specificity, with splicing playing mostly a complementary role; except for the brain, which exhibits a more divergent splicing program. Variation in splicing, despite its stochasticity, may play in contrast a comparatively greater role in defining individual phenotypes.
1,131 citations
Paris Descartes University1, Institut Gustave Roussy2, Mount Sinai Hospital3, University of Texas Southwestern Medical Center4, University of Kiel5, Thomas Jefferson University6, Seconda Università degli Studi di Napoli7, University of Toronto8, University of Massachusetts Medical School9, Louisiana State University10, Flanders Institute for Biotechnology11, Ghent University12, Queen Mary University of London13, Cancer Research UK14, Roswell Park Cancer Institute15, Karolinska Institutet16, University of Freiburg17, University of California, San Francisco18, Buck Institute for Research on Aging19, Université Paris-Saclay20, French Institute of Health and Medical Research21, University College London22, University of Rome Tor Vergata23, Northwestern University24, Memorial Sloan Kettering Cancer Center25, National Institutes of Health26, Technion – Israel Institute of Technology27, Johns Hopkins University28, University of Chieti-Pescara29, University of Ulm30, Genentech31, New York University32, Pennsylvania State University33, University of Salento34, Yale University35, Goethe University Frankfurt36, University of Burgundy37, Pasteur Institute38, University of Strasbourg39, University of Zurich40, University of Tokyo41, Technische Universität München42, University of Bern43, University of Michigan44, Medical Research Council45, University of South Australia46, University of Adelaide47, Medical University of South Carolina48, Howard Hughes Medical Institute49, University of Texas at Dallas50, St. John's University51, University of Oviedo52, University of Graz53, Istituto Superiore di Sanità54, Katholieke Universiteit Leuven55, Trinity College, Dublin56, University of Geneva57, University of Amsterdam58, Stony Brook University59, University of Washington60, University of Ferrara61, Royal College of Surgeons in Ireland62, La Trobe University63, University of Buenos Aires64, University of Virginia65, University of Padua66, University of Lisbon67, University of Cambridge68, University of Würzburg69, Soochow University (Suzhou)70, Columbia University71, University of Glasgow72, Foundation for Research & Technology – Hellas73, University of Crete74, Innsbruck Medical University75, Carlos III Health Institute76, Rutgers University77, University of Minnesota78, Harvard University79, City University of New York80, Moscow State University81
TL;DR: The Nomenclature Committee on Cell Death formulates a set of recommendations to help scientists and researchers to discriminate between essential and accessory aspects of cell death.
Abstract: Cells exposed to extreme physicochemical or mechanical stimuli die in an uncontrollable manner, as a result of their immediate structural breakdown. Such an unavoidable variant of cellular demise is generally referred to as ‘accidental cell death’ (ACD). In most settings, however, cell death is initiated by a genetically encoded apparatus, correlating with the fact that its course can be altered by pharmacologic or genetic interventions. ‘Regulated cell death’ (RCD) can occur as part of physiologic programs or can be activated once adaptive responses to perturbations of the extracellular or intracellular microenvironment fail. The biochemical phenomena that accompany RCD may be harnessed to classify it into a few subtypes, which often (but not always) exhibit stereotyped morphologic features. Nonetheless, efficiently inhibiting the processes that are commonly thought to cause RCD, such as the activation of executioner caspases in the course of apoptosis, does not exert true cytoprotective effects in the mammalian system, but simply alters the kinetics of cellular demise as it shifts its morphologic and biochemical correlates. Conversely, bona fide cytoprotection can be achieved by inhibiting the transduction of lethal signals in the early phases of the process, when adaptive responses are still operational. Thus, the mechanisms that truly execute RCD may be less understood, less inhibitable and perhaps more homogeneous than previously thought. Here, the Nomenclature Committee on Cell Death formulates a set of recommendations to help scientists and researchers to discriminate between essential and accessory aspects of cell death.
809 citations
TL;DR: It is shown that chameleons shift colour through active tuning of a lattice of guanine nanocrystals within a superficial thick layer of dermal iridophores, which allows some species to combine efficient camouflage with spectacular display, while potentially providing passive thermal protection.
Abstract: Many chameleons, and panther chameleons in particular, have the remarkable ability to exhibit complex and rapid colour changes during social interactions such as male contests or courtship. It is generally interpreted that these changes are due to dispersion/aggregation of pigment-containing organelles within dermal chromatophores. Here, combining microscopy, photometric videography and photonic band-gap modelling, we show that chameleons shift colour through active tuning of a lattice of guanine nanocrystals within a superficial thick layer of dermal iridophores. In addition, we show that a deeper population of iridophores with larger crystals reflects a substantial proportion of sunlight especially in the near-infrared range. The organization of iridophores into two superposed layers constitutes an evolutionary novelty for chameleons, which allows some species to combine efficient camouflage with spectacular display, while potentially providing passive thermal protection.
797 citations
TL;DR: In this paper, the authors study how stock markets react to positive and negative events concerned with a firm's corporate social responsibility (CSR), and they show that investors respond strongly negatively to negative events and weakly negatively to positive events.
668 citations
TL;DR: The fundamental theory from signal processing is provided to address parameter choices when estimating and interpreting dynFC and shows how spurious fluctuations in dynFC can arise due to the estimation method when the window length is shorter than the largest wavelength present in both signals.
644 citations
Montreal Heart Institute1, Pennsylvania State University2, Virginia Commonwealth University3, Children's Medical Research Institute4, University of Southern California5, University of Washington6, University of Michigan7, University of California, San Francisco8, Duke University9, University of Geneva10, University of Pennsylvania11, Harvard University12, University of Connecticut13, Centre national de la recherche scientifique14, University of Arizona15, Université de Sherbrooke16, University of Pittsburgh17, Johns Hopkins University18
TL;DR: The Pediatric Acute Lung Injury Consensus Conference developed pediatric-specific definitions for acute respiratory distress syndrome and recommendations regarding treatment and future research priorities intended to promote optimization and consistency of care for children with Pediatrics.
Abstract: Objective: To describe the final recommendations of the Pediatric Acute Lung Injury Consensus Conference. Design: Consensus conference of experts in pediatric acute lung injury. Setting: Not applicable. Subjects: PICU patients with evidence of acute lung injury or acute respiratory distress syndrome. Interventions: None. Methods: A panel of 27 experts met over the course of 2 years to develop a taxonomy to define pediatric acute respiratory distress syndrome and to make recommendations regarding treatment and research priorities. When published, data were lacking a modified Delphi approach emphasizing strong professional agreement was used. Measurements and Main Results: A panel of 27 experts met over the course of 2 years to develop a taxonomy to define pediatric acute respiratory distress syndrome and to make recommendations regarding treatment and research priorities. When published data were lacking a modified Delphi approach emphasizing strong professional agreement was used. The Pediatric Acute Lung Injury Consensus Conference experts developed and voted on a total of 151 recommendations addressing the following topics related to pediatric acute respiratory distress syndrome: 1) Definition, prevalence, and epidemiology; 2) Pathophysiology, comorbidities, and severity; 3) Ventilatory support; 4) Pulmonary-specific ancillary treatment; 5) Nonpulmonary treatment; 6) Monitoring; 7) Noninvasive support and ventilation; 8) Extracorporeal support; and 9) Morbidity and long-term outcomes. There were 132 recommendations with strong agreement and 19 recommendations with weak agreement. Once restated, the final iteration of the recommendations had none with equipoise or disagreement. Conclusions: The Consensus Conference developed pediatric-specific definitions for acute respiratory distress syndrome and recommendations regarding treatment and future research priorities. These are intended to promote optimization and consistency of care for children with pediatric acute respiratory distress syndrome and identify areas of uncertainty requiring further investigation.
624 citations
TL;DR: The roles of mitochondria in the generation of ROS-derived anti-microbial effectors, the interplay of mitochondia and ROS with autophagy and the formation of DNA extracellular traps, and activation of the NLRP3 inflammasome by ROS and mitochondria are discussed.
Abstract: Reactive oxygen species (ROS) are integral components of multiple cellular pathways even though excessive or inappropriately localized ROS damage cells. ROS function as anti-microbial effector molecules and as signaling molecules that regulate such processes as NF-kB transcriptional activity, the production of DNA-based neutrophil extracellular traps (NETs), and autophagy. The main sources of cellular ROS are mitochondria and NADPH oxidases (NOXs). In contrast to NOX-generated ROS, ROS produced in the mitochondria (mtROS) were initially considered to be unwanted by-products of oxidative metabolism. Increasing evidence indicates that mtROS have been incorporated into signaling pathways including those regulating immune responses and autophagy. As metabolic hubs, mitochondria facilitate crosstalk between the metabolic state of the cell with these pathways. Mitochondria and ROS are thus a nexus of multiple pathways that determine the response of cells to disruptions in cellular homeostasis such as infection, sterile damage, and metabolic imbalance. In this review, we discuss the roles of mitochondria in the generation of ROS-derived anti-microbial effectors, the interplay of mitochondria and ROS with autophagy and the formation of DNA extracellular traps, and activation of the NLRP3 inflammasome by ROS and mitochondria.
TL;DR: Survival rates of most types of all-ceramic SCs were similar to those reported for metal-ceramic SCs, both in anterior and posterior regions, and feldspathic/silica-based ceramics should be limited to applications in the anterior region.
Stanford University1, University of Geneva2, VA Palo Alto Healthcare System3, National Institutes of Health4, Douglas Mental Health University Institute5, McGill University6, Heidelberg University7, King's College London8, Trinity College, Dublin9, Université de Montréal10, Commissariat à l'énergie atomique et aux énergies alternatives11, Charité12, University of Vermont13, University of Nottingham14, French Institute of Health and Medical Research15, Paris Descartes University16, University of Toronto17, University of Cambridge18, Dresden University of Technology19, Medical Research Council20, Allen Institute for Brain Science21, Helen Wills Neuroscience Institute22
TL;DR: It is shown that functional brain networks defined with resting-state functional magnetic resonance imaging can be recapitulated by using measures of correlated gene expression in a post mortem brain tissue data set.
Abstract: During rest, brain activity is synchronized between different regions widely distributed throughout the brain, forming functional networks. However, the molecular mechanisms supporting functional connectivity remain undefined. We show that functional brain networks defined with resting-state functional magnetic resonance imaging can be recapitulated by using measures of correlated gene expression in a post mortem brain tissue data set. The set of 136 genes we identify is significantly enriched for ion channels. Polymorphisms in this set of genes significantly affect resting-state functional connectivity in a large sample of healthy adolescents. Expression levels of these genes are also significantly associated with axonal connectivity in the mouse. The results provide convergent, multimodal evidence that resting-state functional networks correlate with the orchestrated activity of dozens of genes linked to ion channel activity and synaptic function.
TL;DR: It is argued that DNA replication stress should be considered as a hallmark of cancer because it likely drives cancer development and is very prevalent.
Abstract: Human cancers share properties referred to as hallmarks, among which sustained proliferation, escape from apoptosis, and genomic instability are the most pervasive. The sustained proliferation hallmark can be explained by mutations in oncogenes and tumor suppressors that regulate cell growth, whereas the escape from apoptosis hallmark can be explained by mutations in the TP53, ATM, or MDM2 genes. A model to explain the presence of the three hallmarks listed above, as well as the patterns of genomic instability observed in human cancers, proposes that the genes driving cell proliferation induce DNA replication stress, which, in turn, generates genomic instability and selects for escape from apoptosis. Here, we review the data that support this model, as well as the mechanisms by which oncogenes induce replication stress. Further, we argue that DNA replication stress should be considered as a hallmark of cancer because it likely drives cancer development and is very prevalent.
TL;DR: In this paper, an overview of the interplay between quantum information theory and thermodynamics of quantum systems is presented. But this is not a comprehensive review of the diverse field of quantum thermodynamics; rather, it is a convenient entry point for the thermo-curious information theorist.
Abstract: This topical review article gives an overview of the interplay between quantum information theory and thermodynamics of quantum systems. We focus on several trending topics including the foundations of statistical mechanics, resource theories, entanglement in thermodynamic settings, fluctuation theorems and thermal machines. This is not a comprehensive review of the diverse field of quantum thermodynamics; rather, it is a convenient entry point for the thermo-curious information theorist. Furthermore this review should facilitate the unification and understanding of different interdisciplinary approaches emerging in research groups around the world.
TL;DR: A discrete-variable quantum key distribution system that is capable of distributing a provably-secure cryptographic key over 307 kilometres is demonstrated at a telecom wavelength.
Abstract: A discrete-variable quantum key distribution system that is capable of distributing a provably-secure cryptographic key over 307 kilometres is demonstrated at a telecom wavelength.
TL;DR: The results demonstrate the microbiota as a key factor orchestrating the overall energy homeostasis during increased demand, leading to altered intestinal gene expression promoting tissue remodeling and suppression of apoptosis.
TL;DR: In this article, the results from six different IceCube searches for astrophysical neutrinos in a maximum-likelihood analysis are combined, and the combined event sample features high-statistics samples of shower-like and track-like events.
Abstract: Evidence for an extraterrestrial flux of high-energy neutrinos has now been found in multiple searches with the IceCube detector. The first solid evidence was provided by a search for neutrino events with deposited energies greater than or similar to 30 TeV and interaction vertices inside the instrumented volume. Recent analyses suggest that the extraterrestrial flux extends to lower energies and is also visible with throughgoing, nu(mu)-induced tracks from the Northern Hemisphere. Here, we combine the results from six different IceCube searches for astrophysical neutrinos in a maximum-likelihood analysis. The combined event sample features high-statistics samples of shower-like and track-like events. The data are fit in up to three observables: energy, zenith angle, and event topology. Assuming the astrophysical neutrino flux to be isotropic and to consist of equal flavors at Earth, the all-flavor spectrum with neutrino energies between 25 TeV and 2.8 PeV is well described by an unbroken power law with best-fit spectral index -2.50 +/- 0.09 and a flux at 100 TeV of (6.7(-1.2)(+1.1)) x 10(-18) GeV-1 s(-1) sr(-1) cm(-2). Under the same assumptions, an unbroken power law with index -2 is disfavored with a significance of 3.8 sigma (p = 0.0066%) with respect to the best fit. This significance is reduced to 2.1 sigma (p = 1.7%) if instead we compare the best fit to a spectrum with index -2 that has an exponential cut-off at high energies. Allowing the electron-neutrino flux to deviate from the other two flavors, we find a nu(e) fraction of 0.18 +/- 0.11 at Earth. The sole production of electron neutrinos, which would be characteristic of neutron-decay-dominated sources, is rejected with a significance of 3.6 sigma ( p = 0.014%).
Broad Institute1, Tehran University of Medical Sciences2, George Washington University3, European Bioinformatics Institute4, Sapienza University of Rome5, Temple University6, Tomsk State University7, University of Notre Dame8, French Institute of Health and Medical Research9, Centre national de la recherche scientifique10, Imperial College London11, James Cook University12, Massachusetts Institute of Technology13, Simon Fraser University14, University of California, Davis15, Institut de recherche pour le développement16, Kansas State University17, Foundation for Research & Technology – Hellas18, University of Perugia19, Virginia Tech20, University of Nevada, Las Vegas21, Baylor College of Medicine22, Boston College23, Harvard University24, University of Manchester25, University of California, San Francisco26, University of Cyprus27, National Health Laboratory Service28, University of Crete29, Kenya Medical Research Institute30, University of Arizona31, University of Pennsylvania32, Indian Council of Medical Research33, New Mexico State University34, Liverpool School of Tropical Medicine35, Vanderbilt University Medical Center36, Vanderbilt University37, Swiss Institute of Bioinformatics38, University of Geneva39, Texas A&M University40, Chiang Mai University41, Oswaldo Cruz Foundation42, Rio de Janeiro State University43, Indiana University44, University of Santiago de Compostela45, Wellcome Trust Sanger Institute46, Liverpool John Moores University47, University of Georgia48, Harvey Mudd College49, University of California, Irvine50, University of Groningen51, Centers for Disease Control and Prevention52, Biogen Idec53
TL;DR: The authors investigated the genomic basis of vectorial capacity and explore new avenues for vector control, sequenced the genomes of 16 anopheline mosquito species from diverse locations spanning ~100 million years of evolution Comparative analyses show faster rates of gene gain and loss, elevated gene shuffling on the X chromosome, and more intron losses, relative to Drosophila.
Abstract: Variation in vectorial capacity for human malaria among Anopheles mosquito species is determined by many factors, including behavior, immunity, and life history To investigate the genomic basis of vectorial capacity and explore new avenues for vector control, we sequenced the genomes of 16 anopheline mosquito species from diverse locations spanning ~100 million years of evolution Comparative analyses show faster rates of gene gain and loss, elevated gene shuffling on the X chromosome, and more intron losses, relative to Drosophila Some determinants of vectorial capacity, such as chemosensory genes, do not show elevated turnover but instead diversify through protein-sequence changes This dynamism of anopheline genes and genomes may contribute to their flexible capacity to take advantage of new ecological niches, including adapting to humans as primary hosts
TL;DR: This work proposes that BSC includes body-centered perception (hand, face, and trunk), based on the integration of proprioceptive, vestibular, and visual bodily inputs, and involves spatio-temporal mechanisms integrating multisensory bodily stimuli within peripersonal space (PPS).
TL;DR: The detailed variation with rigidity of the helium flux spectral index is presented for the first time and the spectral index progressively hardens at rigidities larger than 100 GV.
Abstract: Knowledge of the precise rigidity dependence of the helium flux is important in understanding the
origin, acceleration, and propagation of cosmic rays. A precise measurement of the helium flux in primary
cosmic rays with rigidity (momentum/charge) from 1.9 GV to 3 TV based on 50 million events is presented
and compared to the proton flux. The detailed variation with rigidity of the helium flux spectral index is
presented for the first time. The spectral index progressively hardens at rigidities larger than 100 GV. The
rigidity dependence of the helium flux spectral index is similar to that of the proton spectral index though
the magnitudes are different. Remarkably, the spectral index of the proton to helium flux ratio increases
with rigidity up to 45 GV and then becomes constant; the flux ratio above 45 GV is well described by a
single power law.
TL;DR: The fabrication of stable sandwiched heterostructures by encapsulating atomically thin black phosphorus between hexagonal boron nitride layers to realize ultra-clean interfaces that allow a high field-effect mobility and ensure that the quality of black phosphorus remains high under ambient conditions.
Abstract: Black phosphorus is an atomically thin material that exhibits excellent properties for electronics applications, but these degrade in atmospheric conditions. Here, the authors demonstrate the fabrication of stable, ultra-clean and high-mobility black phosphorus sandwiched between the layers of boron nitride.
TL;DR: In the ultraviolet the Neptune-mass exoplanet GJ 436b (also known as Gliese 436b) has transit depths of 56.3 ± 3.5% (1σ), far beyond the 0.69% optical transit depth, and it is inferred that the planet is surrounded and trailed by a large exospheric cloud composed mainly of hydrogen atoms.
Abstract: In the ultraviolet spectrum, the Neptune-mass exoplanet GJ 436b is shown to have transit depths far greater than those seen in the optical spectrum, indicating that it is surrounded and trailed by a large cloud composed mainly of hydrogen atoms. Observations of the Neptune-mass exoplanet GJ 436b in the ultraviolet reveal a transit signature that is much deeper and longer than in the optical spectrum, an indication that it is surrounded and trailed by a large cloud of gas escaping from the planetary atmosphere. Numerical simulations indicate that in the ultraviolet GJ 436b looks like a giant comet. The authors propose that the gaseous 'tail' is composed mainly of hydrogen atoms and suggest that the exoplanet may have lost 10% of its atmosphere in its early life. Exoplanets orbiting close to their parent stars may lose some fraction of their atmospheres because of the extreme irradiation1,2,3,4,5,6. Atmospheric mass loss primarily affects low-mass exoplanets, leading to the suggestion that hot rocky planets7,8,9 might have begun as Neptune-like10,11,12,13,14,15,16, but subsequently lost all of their atmospheres; however, no confident measurements have hitherto been available. The signature of this loss could be observed in the ultraviolet spectrum, when the planet and its escaping atmosphere transit the star, giving rise to deeper and longer transit signatures than in the optical spectrum17. Here we report that in the ultraviolet the Neptune-mass exoplanet GJ 436b (also known as Gliese 436b) has transit depths of 56.3 ± 3.5% (1σ), far beyond the 0.69% optical transit depth. The ultraviolet transits repeatedly start about two hours before, and end more than three hours after the approximately one hour optical transit, which is substantially different from one previous claim6 (based on an inaccurate ephemeris). We infer from this that the planet is surrounded and trailed by a large exospheric cloud composed mainly of hydrogen atoms. We estimate a mass-loss rate in the range of about 108–109 grams per second, which is far too small to deplete the atmosphere of a Neptune-like planet in the lifetime of the parent star, but would have been much greater in the past.
TL;DR: It is suggested that EEG microstates represent a promising neurophysiological tool for understanding and assessing brain network dynamics on a millisecond timescale in health and disease.
University College London1, University of London2, Erasmus University Rotterdam3, Leiden University Medical Center4, Sunnybrook Health Sciences Centre5, University of Toronto6, University Health Network7, Laval University8, University of Brescia9, University of Milan10, University of Cambridge11, Karolinska Institutet12, Karolinska University Hospital13, University of Geneva14, University of Western Ontario15, University of Florence16
TL;DR: Structural imaging and cognitive changes can be identified 5-10 years before expected onset of symptoms in asymptomatic adults at risk of genetic frontotemporal dementia, which could help to define biomarkers that can stage presymPTomatic disease and track disease progression.
Abstract: Summary Background Frontotemporal dementia is a highly heritable neurodegenerative disorder. In about a third of patients, the disease is caused by autosomal dominant genetic mutations usually in one of three genes: progranulin ( GRN ), microtubule-associated protein tau ( MAPT ), or chromosome 9 open reading frame 72 ( C9orf72 ). Findings from studies of other genetic dementias have shown neuroimaging and cognitive changes before symptoms onset, and we aimed to identify whether such changes could be shown in frontotemporal dementia. Methods We recruited participants to this multicentre study who either were known carriers of a pathogenic mutation in GRN, MAPT , or C9orf72 , or were at risk of carrying a mutation because a first-degree relative was a known symptomatic carrier. We calculated time to expected onset as the difference between age at assessment and mean age at onset within the family. Participants underwent a standardised clinical assessment and neuropsychological battery. We did MRI and generated cortical and subcortical volumes using a parcellation of the volumetric T1-weighted scan. We used linear mixed-effects models to examine whether the association of neuropsychology and imaging measures with time to expected onset of symptoms differed between mutation carriers and non-carriers. Findings Between Jan 30, 2012, and Sept 15, 2013, we recruited participants from 11 research sites in the UK, Italy, the Netherlands, Sweden, and Canada. We analysed data from 220 participants: 118 mutation carriers (40 symptomatic and 78 asymptomatic) and 102 non-carriers. For neuropsychology measures, we noted the earliest significant differences between mutation carriers and non-carriers 5 years before expected onset, when differences were significant for all measures except for tests of immediate recall and verbal fluency. We noted the largest Z score differences between carriers and non-carriers 5 years before expected onset in tests of naming (Boston Naming Test −0·7; SE 0·3) and executive function (Trail Making Test Part B, Digit Span backwards, and Digit Symbol Task, all −0·5, SE 0·2). For imaging measures, we noted differences earliest for the insula (at 10 years before expected symptom onset, mean volume as a percentage of total intracranial volume was 0·80% in mutation carriers and 0·84% in non-carriers; difference −0·04, SE 0·02) followed by the temporal lobe (at 10 years before expected symptom onset, mean volume as a percentage of total intracranial volume 8·1% in mutation carriers and 8·3% in non-carriers; difference −0·2, SE 0·1). Interpretation Structural imaging and cognitive changes can be identified 5–10 years before expected onset of symptoms in asymptomatic adults at risk of genetic frontotemporal dementia. These findings could help to define biomarkers that can stage presymptomatic disease and track disease progression, which will be important for future therapeutic trials. Funding Centres of Excellence in Neurodegeneration.
TL;DR: Tightly regulated levels of ROS are critical for MSC terminal differentiation, although the precise sources, localization, levels and the exact species of ROS implicated remain to be determined.
Abstract: Mesenchymal stromal cells (MSCs) are promising candidates for tissue engineering and regenerative medicine. The multipotent stem cell component of MSC isolates is able to differentiate into derivatives of the mesodermal lineage including adipocytes, osteocytes, chondrocytes, and myocytes. Many common pathways have been described in the regulation of adipogenesis and osteogenesis. However, stimulation of osteogenesis appears to suppress adipogenesis and vice-versa. Increasing evidence implicates a tight regulation of these processes by reactive oxygen species (ROS). ROS are short-lived oxygen-containing molecules that display high chemical reactivity toward DNA, RNA, proteins, and lipids. Mitochondrial complexes I and III, and the NADPH oxidase isoform NOX4 are major sources of ROS production during MSC differentiation. ROS are thought to interact with several pathways that affect the transcription machinery required for MSC differentiation including the Wnt, Hedgehog, and FOXO signaling cascades. On the other hand, elevated levels of ROS, defined as oxidative stress, lead to arrest of the MSC cell cycle and apoptosis. Tightly regulated levels of ROS are therefore critical for MSC terminal differentiation, although the precise sources, localization, levels and the exact species of ROS implicated remain to be determined. This review provides a detailed overview of the influence of ROS on adipogenic and osteogenic differentiation in MSCs.
TL;DR: The refined characterization of the macrophage subpopulations can be useful in designing new strategies, supplementing those already established for the treatment of diseases using macrophages as a therapeutic target.
Abstract: Monocytes are considered to be precursor cells of the mononuclear phagocytic system, and macrophages are one of the leading members of this cellular system. Macrophages play highly diverse roles in maintaining an organism’s integrity by either directly participating in pathogen elimination or repairing tissue under sterile inflammatory conditions. There are different subpopulations of macrophages and each one has its own characteristics and functions. In this review, we summarize present knowledge on the polarization of macrophages that allows the generation of subpopulations called: classically activated macrophages or M1, and alternative activated macrophages or M2. Furthermore, there are macrophages that still their origin and characterization remain unclear but have been involved as main players in some human pathologies. Thus, we also review three other categories of macrophages: tumor-associated macrophages (TAM), CD169+ macrophages and the recently named TCR+ macrophages. Based on the literature, we provide information on the molecular characterization of these macrophage subpopulations and their specific involvement in several human pathologies such as cancer, infectious diseases, obesity and asthma. The refined characterization of the macrophage subpopulations can be useful in designing new strategies, supplementing those already established for the treatment of diseases using macrophages as a therapeutic target
TL;DR: In this article, a search for new phenomena in final states with an energetic jet and large missing transverse momentum was performed using 20.3 fb(-1) of root s = 8 TeV data collected in 2012.
Abstract: Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb(-1) of root s = 8 TeV data collected in 2012 ...
TL;DR: A selection pathway for commensal bacteria–specific CD4+ T cells in the intestine is defined and it is suggested that this process is dysregulated in human IBD.
Abstract: Inflammatory CD4(+) T cell responses to self or commensal bacteria underlie the pathogenesis of autoimmunity and inflammatory bowel disease (IBD), respectively. Although selection of self-specific T cells in the thymus limits responses to mammalian tissue antigens, the mechanisms that control selection of commensal bacteria-specific T cells remain poorly understood. Here, we demonstrate that group 3 innate lymphoid cell (ILC3)-intrinsic expression of major histocompatibility complex class II (MHCII) is regulated similarly to thymic epithelial cells and that MHCII(+) ILC3s directly induce cell death of activated commensal bacteria-specific T cells. Further, MHCII on colonic ILC3s was reduced in pediatric IBD patients. Collectively, these results define a selection pathway for commensal bacteria-specific CD4(+) T cells in the intestine and suggest that this process is dysregulated in human IBD.
TL;DR: This work identifies the host transmembrane protein SERINC5, and to a lesser extent SERINC3, as a potent inhibitor of HIV-1 particle infectivity that is counteracted by Nef.
Abstract: HIV-1 Nef, a protein important for the development of AIDS, has well-characterized effects on host membrane trafficking and receptor downregulation. By an unidentified mechanism, Nef increases the intrinsic infectivity of HIV-1 virions in a host-cell-dependent manner. Here we identify the host transmembrane protein SERINC5, and to a lesser extent SERINC3, as a potent inhibitor of HIV-1 particle infectivity that is counteracted by Nef. SERINC5 localizes to the plasma membrane, where it is efficiently incorporated into budding HIV-1 virions and impairs subsequent virion penetration of susceptible target cells. Nef redirects SERINC5 to a Rab7-positive endosomal compartment and thereby excludes it from HIV-1 particles. The ability to counteract SERINC5 was conserved in Nef encoded by diverse primate immunodeficiency viruses, as well as in the structurally unrelated glycosylated Gag from murine leukaemia virus. These examples of functional conservation and convergent evolution emphasize the fundamental importance of SERINC5 as a potent anti-retroviral factor.