Showing papers by "University of Montpellier published in 2013"
University of St Andrews1, University of Oldenburg2, Natural History Museum3, Naturalis4, Centre national de la recherche scientifique5, Michigan State University6, University of Lausanne7, University of Wyoming8, Queen Mary University of London9, University of Sheffield10, International Institute for Applied Systems Analysis11, University of Oslo12, University of Vienna13, University of Vermont14, University of East Anglia15, Spanish National Research Council16, University of Cambridge17, University of Konstanz18, University of Zurich19, Royal Botanic Garden Edinburgh20, Harvard University21, Autonomous University of Madrid22, Swiss Federal Institute of Aquatic Science and Technology23, Boston University24, Max Planck Society25, University of Neuchâtel26, University of North Carolina at Chapel Hill27, Lehigh University28, American Museum of Natural History29, University of Montpellier30, University of Liverpool31, Jagiellonian University32, Uppsala University33, German Primate Center34
TL;DR: A perspective on the context and evolutionary significance of hybridization during speciation is offered, highlighting issues of current interest and debate and suggesting that the Dobzhansky–Muller model of hybrid incompatibilities requires a broader interpretation.
Abstract: Hybridization has many and varied impacts on the process of speciation. Hybridization may slow or reverse differentiation by allowing gene flow and recombination. It may accelerate speciation via adaptive introgression or cause near-instantaneous speciation by allopolyploidization. It may have multiple effects at different stages and in different spatial contexts within a single speciation event. We offer a perspective on the context and evolutionary significance of hybridization during speciation, highlighting issues of current interest and debate. In secondary contact zones, it is uncertain if barriers to gene flow will be strengthened or broken down due to recombination and gene flow. Theory and empirical evidence suggest the latter is more likely, except within and around strongly selected genomic regions. Hybridization may contribute to speciation through the formation of new hybrid taxa, whereas introgression of a few loci may promote adaptive divergence and so facilitate speciation. Gene regulatory networks, epigenetic effects and the evolution of selfish genetic material in the genome suggest that the Dobzhansky-Muller model of hybrid incompatibilities requires a broader interpretation. Finally, although the incidence of reinforcement remains uncertain, this and other interactions in areas of sympatry may have knock-on effects on speciation both within and outside regions of hybridization.
1,715 citations
TL;DR: This work proves an abstract convergence result for descent methods satisfying a sufficient-decrease assumption, and allowing a relative error tolerance, that guarantees the convergence of bounded sequences under the assumption that the function f satisfies the Kurdyka–Łojasiewicz inequality.
Abstract: In view of the minimization of a nonsmooth nonconvex function f, we prove an abstract convergence result for descent methods satisfying a sufficient-decrease assumption, and allowing a relative error tolerance. Our result guarantees the convergence of bounded sequences, under the assumption that the function f satisfies the Kurdyka–Łojasiewicz inequality. This assumption allows to cover a wide range of problems, including nonsmooth semi-algebraic (or more generally tame) minimization. The specialization of our result to different kinds of structured problems provides several new convergence results for inexact versions of the gradient method, the proximal method, the forward–backward splitting algorithm, the gradient projection and some proximal regularization of the Gauss–Seidel method in a nonconvex setting. Our results are illustrated through feasibility problems, or iterative thresholding procedures for compressive sensing.
1,282 citations
TL;DR: In this article, the reactivity of a class of high-capacity oxides with a single redox cation has been investigated and it has been shown that these oxides exhibit sustainable reversible capacities as high as 230 mAh/g−1 and good cycling behavior with no signs of voltage decay.
Abstract: Li-ion batteries have contributed to the commercial success of portable electronics and may soon dominate the electric transportation market provided that major scientific advances including new materials and concepts are developed. Classical positive electrodes for Li-ion technology operate mainly through an insertion-deinsertion redox process involving cationic species. However, this mechanism is insufficient to account for the high capacities exhibited by the new generation of Li-rich (Li1+xNiyCozMn(1−x−y−z)O2) layered oxides that present unusual Li reactivity. In an attempt to overcome both the inherent composition and the structural complexity of this class of oxides, we have designed structurally related Li2Ru1−ySnyO3 materials that have a single redox cation and exhibit sustainable reversible capacities as high as 230 mA h g−1. Moreover, they present good cycling behaviour with no signs of voltage decay and a small irreversible capacity. We also unambiguously show, on the basis of an arsenal of characterization techniques, that the reactivity of these high-capacity materials towards Li entails cumulative cationic (Mn+→M(n+1)+) and anionic (O2−→O22−) reversible redox processes, owing to the d-sp hybridization associated with a reductive coupling mechanism. Because Li2MO3 is a large family of compounds, this study opens the door to the exploration of a vast number of high-capacity materials.
1,109 citations
TL;DR: The very accurate data show that the positron fraction is steadily increasing from 10 to ∼ 250 GeV, but, from 20 to 250 GeV, the slope decreases by an order of magnitude, showing the existence of new physical phenomena.
Abstract: A precision measurement by the Alpha Magnetic Spectrometer on the International Space Station of the positron fraction in primary cosmic rays in the energy range from 0.5 to 350 GeV based on 6.8 × 10(6) positron and electron events is presented. The very accurate data show that the positron fraction is steadily increasing from 10 to ∼ 250 GeV, but, from 20 to 250 GeV, the slope decreases by an order of magnitude. The positron fraction spectrum shows no fine structure, and the positron to electron ratio shows no observable anisotropy. Together, these features show the existence of new physical phenomena.
1,100 citations
TL;DR: Novel knowledge and gaps on PGPR modes of action and signals are addressed, recent progress on the links between plant morphological and physiological effects induced by PGPR are highlighted, and the importance of taking into account the size, diversity, and gene expression patterns of PGPR assemblages in the rhizosphere to better understand their impact on plant growth and functioning is shown.
Abstract: The rhizosphere supports the development and activity of a huge and diversified microbial community, including microorganisms capable to promote plant growth. Among the latter, plant growth-promoting rhizobacteria (PGPR) colonize roots of monocots and dicots, and enhance plant growth by direct and indirect mechanisms. Modification of root system architecture by PGPR implicates the production of phytohormones and other signals that lead, mostly, to enhanced lateral root branching and development of root hairs. PGPR also modify root functioning, improve plant nutrition and influence the physiology of the whole plant. Recent results provided first clues as to how PGPR signals could trigger these plant responses. Whether local and/or systemic, the plant molecular pathways involved remain often unknown. From an ecological point of view, it emerged that PGPR form coherent functional groups, whose rhizosphere ecology is influenced by a myriad of abiotic and biotic factors in natural and agricultural soils, and these factors can in turn modulate PGPR effects on roots. In this paper, we address novel knowledge and gaps on PGPR modes of action and signals, and highlight recent progress on the links between plant morphological and physiological effects induced by PGPR. We also show the importance of taking into account the size, diversity, and gene expression patterns of PGPR assemblages in the rhizosphere to better understand their impact on plant growth and functioning. Integrating mechanistic and ecological knowledge on PGPR populations in soil will be a prerequisite to develop novel management strategies for sustainable agriculture.
1,028 citations
TL;DR: In this article, a catalog of gamma-ray pulsar detections using three years of data acquired by the Large Area Telescope (LAT) on the Fermi satellite is presented.
Abstract: This catalog summarizes 117 high-confidence > 0.1 GeV gamma-ray pulsar detections using three years of data acquired by the Large Area Telescope (LAT) on the Fermi satellite. Half are neutron stars discovered using LAT data, through periodicity searches in gamma-ray and radio data around LAT unassociated source positions. The 117 pulsars are evenly divided into three groups: millisecond pulsars, young radio-loud pulsars, and young radio-quiet pulsars. We characterize the pulse profiles and energy spectra and derive luminosities when distance information exists. Spectral analysis of the off-peak phase intervals indicates probable pulsar wind nebula emission for four pulsars, and off-peak magnetospheric emission for several young and millisecond pulsars. We compare the gamma-ray properties with those in the radio, optical, and X-ray bands. We provide flux limits for pulsars with no observed gamma-ray emission, highlighting a small number of gamma-faint, radio-loud pulsars. The large, varied gamma-ray pulsar sample constrains emission models. Fermi's selection biases complement those of radio surveys, enhancing comparisons with predicted population distributions.
929 citations
Federal Urdu University1, Columbia University2, Woods Hole Oceanographic Institution3, Addis Ababa University4, Indian Institute of Tropical Meteorology5, University of Trieste6, Swiss Federal Institute for Forest, Snow and Landscape Research7, University of Bergen8, University of Montpellier9, University of Chile10, Austral University of Chile11, Australian Antarctic Division12, University of Tasmania13, National Oceanic and Atmospheric Administration14, University of Mainz15, Xishuangbanna Tropical Botanical Garden16, Nepal Academy of Science and Technology17, Chinese Academy of Sciences18, University of Melbourne19, Complutense University of Madrid20, Université catholique de Louvain21, University of the Witwatersrand22, Hydrologic Research Center23, University of Bern24, University of Helsinki25, Northern Arizona University26, Fukushima University27, Stockholm University28, Université Paris-Saclay29, National Institute of Water and Atmospheric Research30, University of Giessen31, Swansea University32, Desert Research Institute33, National Scientific and Technical Research Council34, British Antarctic Survey35, Nagoya University36, University of Brighton37, Florida State University38, Alfred Wegener Institute for Polar and Marine Research39, University of New South Wales40, University of Exeter41, Centro de Estudios Científicos42, University of Florence43, University of Texas at Austin44, Russian Academy of Sciences45, University of Washington46, National Centre for Antarctic and Ocean Research47, University of Arizona48, Ghent University49, University of Ottawa50, University of Copenhagen51, University of Colorado Boulder52, Shinshu University53
TL;DR: The authors reconstructed past temperatures for seven continental-scale regions during the past one to two millennia and found that the most coherent feature in nearly all of the regional temperature reconstructions is a long-term cooling trend, which ended late in the nineteenth century.
Abstract: Past global climate changes had strong regional expression To elucidate their spatio-temporal pattern, we reconstructed past temperatures for seven continental-scale regions during the past one to two millennia The most coherent feature in nearly all of the regional temperature reconstructions is a long-term cooling trend, which ended late in the nineteenth century At multi-decadal to centennial scales, temperature variability shows distinctly different regional patterns, with more similarity within each hemisphere than between them There were no globally synchronous multi-decadal warm or cold intervals that define a worldwide Medieval Warm Period or Little Ice Age, but all reconstructions show generally cold conditions between ad 1580 and 1880, punctuated in some regions by warm decades during the eighteenth century The transition to these colder conditions occurred earlier in the Arctic, Europe and Asia than in North America or the Southern Hemisphere regions Recent warming reversed the long-term cooling; during the period ad 1971–2000, the area-weighted average reconstructed temperature was higher than any other time in nearly 1,400 years
885 citations
TL;DR: The characteristic pion-decay feature is detected in the gamma-ray spectra of two SNRs, IC 443 and W44, with the Fermi Large Area Telescope, providing direct evidence that cosmic-ray protons are accelerated in SNRs.
Abstract: Cosmic rays are particles (mostly protons) accelerated to relativistic speeds. Despite wide agreement that supernova remnants (SNRs) are the sources of galactic cosmic rays, unequivocal evidence for the acceleration of protons in these objects is still lacking. When accelerated protons encounter interstellar material, they produce neutral pions, which in turn decay into gamma rays. This offers a compelling way to detect the acceleration sites of protons. The identification of pion-decay gamma rays has been difficult because high-energy electrons also produce gamma rays via bremsstrahlung and inverse Compton scattering. We detected the characteristic pion-decay feature in the gamma-ray spectra of two SNRs, IC 443 and W44, with the Fermi Large Area Telescope. This detection provides direct evidence that cosmic-ray protons are accelerated in SNRs.
846 citations
TL;DR: The Cherenkov Telescope Array (CTA) as discussed by the authors is a very high-energy (VHE) gamma ray observatory with an international collaboration with more than 1000 members from 27 countries in Europe, Asia, Africa and North and South America.
701 citations
TL;DR: Responding to climate change will likely require that the quantitative traits of populations again match their environments, and it is found that genetic differentiation between populations and clinal variation along environmental gradients were very common.
Abstract: Evolutionary responses are required for tree populations to be able to track climate change. Results of 250 years of common garden experiments show that most forest trees have evolved local adaptation, as evidenced by the adaptive differentiation of populations in quantitative traits, reflecting environmental conditions of population origins. On the basis of the patterns of quantitative variation for 19 adaptation-related traits studied in 59 tree species (mostly temperate and boreal species from the Northern hemisphere), we found that genetic differentiation between populations and clinal variation along environmental gradients were very common (respectively, 90% and 78% of cases). Thus, responding to climate change will likely require that the quantitative traits of populations again match their environments. We examine what kind of information is needed for evaluating the potential to respond, and what information is already available. We review the genetic models related to selection responses, and what is known currently about the genetic basis of the traits. We address special problems to be found at the range margins, and highlight the need for more modeling to understand specific issues at southern and northern margins. We need new common garden experiments for less known species. For extensively studied species, new experiments are needed outside the current ranges. Improving genomic information will allow better prediction of responses. Competitive and other interactions within species and interactions between species deserve more consideration. Despite the long generation times, the strong background in quantitative genetics and growing genomic resources make forest trees useful species for climate change research. The greatest adaptive response is expected when populations are large, have high genetic variability, selection is strong, and there is ecological opportunity for establishment of better adapted genotypes.
687 citations
TL;DR: The most unusual, and thus irreplaceable, functions performed by species in three different species-rich ecosystems are fulfilled by only the rare species in these ecosystems.
Abstract: Around the world, the human-induced collapses of populations and species have triggered a sixth mass extinction crisis, with rare species often being the first to disappear. Although the role of species diversity in the maintenance of ecosystem processes has been widely investigated, the role of rare species remains controversial. A critical issue is whether common species insure against the loss of functions supported by rare species. This issue is even more critical in species-rich ecosystems where high functional redundancy among species is likely and where it is thus often assumed that ecosystem functioning is buffered against species loss. Here, using extensive datasets of species occurrences and functional traits from three highly diverse ecosystems (846 coral reef fishes, 2,979 alpine plants, and 662 tropical trees), we demonstrate that the most distinct combinations of traits are supported predominantly by rare species both in terms of local abundance and regional occupancy. Moreover, species that have low functional redundancy and are likely to support the most vulnerable functions, with no other species carrying similar combinations of traits, are rarer than expected by chance in all three ecosystems. For instance, 63% and 98% of fish species that are likely to support highly vulnerable functions in coral reef ecosystems are locally and regionally rare, respectively. For alpine plants, 32% and 89% of such species are locally and regionally rare, respectively. Remarkably, 47% of fish species and 55% of tropical tree species that are likely to support highly vulnerable functions have only one individual per sample on average. Our results emphasize the importance of rare species conservation, even in highly diverse ecosystems, which are thought to exhibit high functional redundancy. Rare species offer more than aesthetic, cultural, or taxonomic diversity value; they disproportionately increase the potential breadth of functions provided by ecosystems across spatial scales. As such, they are likely to insure against future uncertainty arising from climate change and the ever-increasing anthropogenic pressures on ecosystems. Our results call for a more detailed understanding of the role of rarity and functional vulnerability in ecosystem functioning.
TL;DR: What has been learnt about the myriad roles of auxin during lateral root formation in Arabidopsis is reviewed to reflect the complexity of the phytohormone's role in root development.
École Polytechnique Fédérale de Lausanne1, Environment Canada2, University of Montpellier3, United States Department of Energy4, Centre national de la recherche scientifique5, University of Bristol6, VU University Amsterdam7, Oeschger Centre for Climate Change Research8, University of Washington9, University of Victoria10, University of Sheffield11, Auburn University12, Kazan Federal University13, Russian Academy of Sciences14, Lawrence Berkeley National Laboratory15, Max Planck Society16, Lehigh University17
TL;DR: The Wetland and Wetland CH4 Inter-comparison of Models Project (WETCHIMP) as mentioned in this paper investigated the ability to simulate large-scale wetland characteristics and corresponding CH4 emissions.
Abstract: . Global wetlands are believed to be climate sensitive, and are the largest natural emitters of methane (CH4). Increased wetland CH4 emissions could act as a positive feedback to future warming. The Wetland and Wetland CH4 Inter-comparison of Models Project (WETCHIMP) investigated our present ability to simulate large-scale wetland characteristics and corresponding CH4 emissions. To ensure inter-comparability, we used a common experimental protocol driving all models with the same climate and carbon dioxide (CO2) forcing datasets. The WETCHIMP experiments were conducted for model equilibrium states as well as transient simulations covering the last century. Sensitivity experiments investigated model response to changes in selected forcing inputs (precipitation, temperature, and atmospheric CO2 concentration). Ten models participated, covering the spectrum from simple to relatively complex, including models tailored either for regional or global simulations. The models also varied in methods to calculate wetland size and location, with some models simulating wetland area prognostically, while other models relied on remotely sensed inundation datasets, or an approach intermediate between the two. Four major conclusions emerged from the project. First, the suite of models demonstrate extensive disagreement in their simulations of wetland areal extent and CH4 emissions, in both space and time. Simple metrics of wetland area, such as the latitudinal gradient, show large variability, principally between models that use inundation dataset information and those that independently determine wetland area. Agreement between the models improves for zonally summed CH4 emissions, but large variation between the models remains. For annual global CH4 emissions, the models vary by ±40% of the all-model mean (190 Tg CH4 yr−1). Second, all models show a strong positive response to increased atmospheric CO2 concentrations (857 ppm) in both CH4 emissions and wetland area. In response to increasing global temperatures (+3.4 °C globally spatially uniform), on average, the models decreased wetland area and CH4 fluxes, primarily in the tropics, but the magnitude and sign of the response varied greatly. Models were least sensitive to increased global precipitation (+3.9 % globally spatially uniform) with a consistent small positive response in CH4 fluxes and wetland area. Results from the 20th century transient simulation show that interactions between climate forcings could have strong non-linear effects. Third, we presently do not have sufficient wetland methane observation datasets adequate to evaluate model fluxes at a spatial scale comparable to model grid cells (commonly 0.5°). This limitation severely restricts our ability to model global wetland CH4 emissions with confidence. Our simulated wetland extents are also difficult to evaluate due to extensive disagreements between wetland mapping and remotely sensed inundation datasets. Fourth, the large range in predicted CH4 emission rates leads to the conclusion that there is both substantial parameter and structural uncertainty in large-scale CH4 emission models, even after uncertainties in wetland areas are accounted for.
TL;DR: A review of the geochemistry of serpentinites, based on the compilation of ~900 geochemical data of abyssal, mantle wedge and exhumed serpentinite after subduction, is presented in this paper.
TL;DR: This review examines the preanalytical parameters potentially affecting ccfDNA concentration and fragmentation at each pre Analytical step from blood drawing to the storage of c cfDNA extracts and determined the optimal preanalytic protocols for ccf DNA analysis.
TL;DR: Practical recommendations are provided regarding the definition of local adaptation, the analysis of transplant experiments and the optimisation of the experimental design ofLocal adaptation studies to provide a unified approach for measuring local adaptation and understanding the adaptive divergence of populations in a wide range of biological systems.
Abstract: Patterns of local adaptation are expected to emerge when selection is spatially heterogeneous and sufficiently strong relative to the action of other evolutionary forces. The observation of local adaptation thus provides important insight into evolutionary processes and the adaptive divergence of populations. The detection of local adaptation, however, suffers from several conceptual, statistical and methodological issues. Here, we provide practical recommendations regarding (1) the definition of local adaptation, (2) the analysis of transplant experiments and (3) the optimisation of the experimental design of local adaptation studies. Together, these recommendations provide a unified approach for measuring local adaptation and understanding the adaptive divergence of populations in a wide range of biological systems.
TL;DR: It is shown that, apart from valuing the rarity and richness aspect, commonly quoted justifications based on the usage of phylogenetic diversity as a proxy for functional diversity or evolutionary potential are still based on uncertainties.
Abstract: To date, there is little evidence that phylogenetic diversity has contributed to nature conservation. Here, we discuss the scientific justification of using phylogenetic diversity in conservation and the reasons for its neglect. We show that, apart from valuing the rarity and richness aspect, commonly quoted justifications based on the usage of phylogenetic diversity as a proxy for functional diversity or evolutionary potential are still based on uncertainties. We discuss how a missing guideline through the variety of phylogenetic diversity metrics and their relevance for conservation might be responsible for the hesitation to include phylogenetic diversity in conservation practice. We outline research routes that can help to ease uncertainties and bridge gaps between research and conservation with respect to phylogenetic diversity.
TL;DR: In the field of nanotube synthesis, catalytic chemical vapour deposition (CVD) is the prevailing synthesis method of carbon nanotubes as discussed by the authors, due to its higher degree of control and its scalability.
TL;DR: In this paper, the authors show that the simple and partial Mantel tests are not valid in this case, and their bias remains close to that of the simple Mantel test, and that strong biases are expected under a sampling design and spatial correlation parameter drawn from an actual study.
Abstract: Summary 1. The simple and partial Mantel tests are routinely used in many areas of evolutionary biology to assess the significance of the association between two or more matrices of distances relative to the same pairs of individuals or demes. Partial Mantel tests rather than simple Mantel tests are widely used to assess the relationship between two variables displaying some form of structure. 2. We show that contrary to a widely shared belief, partial Mantel tests are not valid in this case, and their bias remains close to that of the simple Mantel test. 3. We confirm that strong biases are expected under a sampling design and spatial correlation parameter drawn from an actual study. 4. The Mantel tests should not be used in case autocorrelation is suspected in both variables compared under the null hypothesis. We outline alternative strategies. The R code used for our computer simulations is distributed as supporting material.
TL;DR: In this article, a joint experimental and computational systematic exploration of the driving forces that govern encapsulation of active ingredients (solvent, starting material dehydration, drug/material ratio, immersion time, and several consecutive impregnations) and its kinetics of delivery (structure, polarity,...) was performed using a series of porous biocompatible metal-organic frameworks (MOFs) that bear different topologies, connectivities, and chemical compositions.
Abstract: A joint experimental and computational systematic exploration of the driving forces that govern (i) encapsulation of active ingredients (solvent, starting material dehydration, drug/material ratio, immersion time, and several consecutive impregnations) and (i) its kinetics of delivery (structure, polarity, ...) was performed using a series of porous biocompatible metal–organic frameworks (MOFs) that bear different topologies, connectivities, and chemical compositions. The liporeductor cosmetic caffeine was selected as the active molecule. Its encapsulation is a challenge for the cosmetic industry due to its high tendency to crystallize leading to poor loadings (<5 wt %) and uncontrolled releases with a subsequent low efficiency. It was evidenced that caffeine entrapping reaches exceptional payloads up to 50 wt %, while progressive release of this cosmetic agent upon immersion in the simulated physiological media (phosphate buffer solution pH = 7.4 or distilled water pH = 6.3, 37 °C) occurred mainly depend...
TL;DR: For example, Harte et al. as mentioned in this paper found that diamond is a rare mineral, occurring at the part-per-billion level even within the most diamondiferous volcanic host rock although some rare eclogites have been known to contain 10−15% diamond.
Abstract: ### Introduction
Earth’s carbon, derived from planetesimals in the 1 AU region during accretion of the Solar System, still retains similarities to carbon found in meteorites (Marty et al. 2013) even after 4.57 billion years of geological processing. The range in isotopic composition of carbon on Earth versus meteorites is nearly identical and, for both, diamond is a common, if volumetrically minor, carbon mineral (Haggerty 1999). Diamond is one of the three native carbon minerals on Earth (the other two being graphite and lonsdaleite). It can crystallize throughout the mantle below about 150 km and can occur metastably in the crust. Diamond is a rare mineral, occurring at the part-per-billion level even within the most diamondiferous volcanic host rock although some rare eclogites have been known to contain 10–15% diamond. As a trace mineral it is unevenly distributed and, except for occurrences in metamorphosed crustal rocks, it is a xenocrystic phase within the series of volcanic rocks (kimberlites, lamproites, ultramafic lamprohyres), which bring it to the surface and host it. The occurrence of diamond on Earth’s surface results from its unique resistance to alteration/dissolution and the sometimes accidental circumstances of its sampling by the volcanic host rock. Diamonds are usually the chief minerals left from their depth of formation, because intact diamondiferous mantle xenoliths are rare.
Diamond has been intensively studied over the last 40 years to provide extraordinary information on our planet’s interior. For example, from the study of its inclusions, diamond is recognized as the only material sampling the “very deep” mantle to depths exceeding 800 km (Harte et al. 1999; McCammon 2001; Stachel and Harris 2009; Harte 2010) although most crystals (~95%) derive from shallower depths (150 to 250 km). Diamonds are less useful in determining carbon fluxes on Earth because they provide only a small, …
Centre national de la recherche scientifique1, French Institute of Health and Medical Research2, New York University3, Joseph Fourier University4, University of Florence5, University of Montpellier6, University of Angers7, Necker-Enfants Malades Hospital8, Lyon College9, Paris Descartes University10, Pierre-and-Marie-Curie University11
TL;DR: The discovery of multiple pathogenic missense mutations in TUBG1, DYNC1H1 and KIF2A, as well as a single germline mosaic mutation in KIF5C, in subjects with MCD are reported, suggesting that microtubule-dependent mitotic and postmitotic processes are major contributors to the pathogenesis of MCD.
Abstract: The genetic causes of malformations of cortical development (MCD) remain largely unknown. Here we report the discovery of multiple pathogenic missense mutations in TUBG1, DYNC1H1 and KIF2A, as well as a single germline mosaic mutation in KIF5C, in subjects with MCD. We found a frequent recurrence of mutations in DYNC1H1, implying that this gene is a major locus for unexplained MCD. We further show that the mutations in KIF5C, KIF2A and DYNC1H1 affect ATP hydrolysis, productive protein folding and microtubule binding, respectively. In addition, we show that suppression of mouse Tubg1 expression in vivo interferes with proper neuronal migration, whereas expression of altered γ-tubulin proteins in Saccharomyces cerevisiae disrupts normal microtubule behavior. Our data reinforce the importance of centrosomal and microtubule-related proteins in cortical development and strongly suggest that microtubule-dependent mitotic and postmitotic processes are major contributors to the pathogenesis of MCD.
TL;DR: This study demonstrated that MSCs contribute to the generation of an immunosuppressive environment via the inhibition of proinflammatory T cells and the induction of T cells with a regulatory phenotype, which might have important clinical implications for inflammatory and autoimmune diseases.
Abstract: Mesenchymal stem cells (MSCs) are adult, multipotent, stem cells with immunomodulatory properties. The mechanisms involved in the capacity of MSCs to inhibit the proliferation of proinflammatory T lymphocytes, which appear responsible for causing autoimmune disease, have yet to be fully elucidated. One of the underlying mechanisms studied recently is the ability of MSCs to generate T regulatory (Treg) cells in vitro and in vivo from activated peripheral blood mononuclear cells (PBMC), T-CD4+ and also T-CD8+ cells. In the present work we investigated the capacity of MSCs to generate Treg cells using T-CD4+ cells induced to differentiate toward the proinflammatory Th1 and Th17 lineages. MSCs were obtained from mouse bone marrow and characterized according to their surface antigen expression and their multilineage differentiation potential. CD4+ T cells isolated from mouse spleens were induced to differentiate into Th1 or Th17 cells and co-cultured with MSCs added at day 0, 2 or 4 of the differentiation processes. After six days, CD25, Foxp3, IL-17 and IFN-γ expression was assessed by flow cytometry and helios and neuropilin 1 mRNA levels were assessed by RT-qPCR. For the functional assays, the ‘conditioned’ subpopulation generated in the presence of MSCs was cultured with concanavalin A-activated CD4+ T cells labeled with carboxyfluorescein succinimidyl ester. Finally, we used the encephalomyelitis autoimmune diseases (EAE) mouse model, in which mice were injected with MSCs at day 18 and 30 after immunization. At day 50, the mice were euthanized and draining lymph nodes were extracted for Th1, Th17 and Treg detection by flow cytometry. MSCs were able to suppress the proliferation, activation and differentiation of CD4+ T cells induced to differentiate into Th1 and Th17 cells. This substantial suppressive effect was associated with an increase of the percentage of functional induced CD4+CD25+Foxp3+ regulatory T cells and IL-10 secretion. However, using mature Th1 or Th17 cells our results demonstrated that while MSCs suppress the proliferation and phenotype of mature Th1 and Th17 cells they did not generate Treg cells. Finally, we showed that the beneficial effect observed following MSC injection in an EAE mouse model was associated with the suppression of Th17 cells and an increase in the percentage of CD4+CD25+Foxp3+ T lymphocytes when administrated at early stages of the disease. This study demonstrated that MSCs contribute to the generation of an immunosuppressive environment via the inhibition of proinflammatory T cells and the induction of T cells with a regulatory phenotype. Together, these results might have important clinical implications for inflammatory and autoimmune diseases.
TL;DR: The first Fermi-LAT catalog of gamma-ray bursts (GRBs) is presented in this paper. But it is limited to GRBs detected by the Gamma-Ray Burst Monitor (GBM).
Abstract: In three years of observations since the beginning of nominal science operations in August 2008, the Large Area Telescope (LAT) on board the Fermi Gamma Ray Space Telescope has observed high-energy (>20 MeV) \gamma-ray emission from 35 gamma-ray bursts (GRBs). Among these, 28 GRBs have been detected above 100 MeV and 7 GRBs above ~ 20 MeV. The first Fermi-LAT catalog of GRBs is a compilation of these detections and provides a systematic study of high-energy emission from GRBs for the first time. To generate the catalog, we examined 733 GRBs detected by the Gamma-Ray Burst Monitor (GBM) on Fermi and processed each of them using the same analysis sequence. Details of the methodology followed by the LAT collaboration for GRB analysis are provided. We summarize the temporal and spectral properties of the LAT-detected GRBs. We also discuss characteristics of LAT-detected emission such as its delayed onset and longer duration compared to emission detected by the GBM, its power-law temporal decay at late times, and the fact that it is dominated by a power-law spectral component that appears in addition to the usual Band model.
TL;DR: This special issue focuses on evolutionary rescue (ER), the idea that evolution might occur sufficiently fast to arrest population decline and allow population recovery before extinction ensues.
Abstract: There is concern that the rate of environmental change is now exceeding the capacity of many populations to adapt. Mitigation of biodiversity loss requires science that integrates both ecological and evolutionary responses of populations and communities to rapid environmental change, and can identify the conditions that allow the recovery of declining populations. This special issue focuses on evolutionary rescue (ER), the idea that evolution might occur sufficiently fast to arrest population decline and allow population recovery before extinction ensues. ER emphasizes a shift to a perspective on evolutionary dynamics that focuses on short time-scales, genetic variants of large effects and absolute rather than relative fitness. The contributions in this issue reflect the state of field; the articles address the latest conceptual developments, and report novel theoretical and experimental results. The examples in this issue demonstrate that this burgeoning area of research can inform problems of direct practical concern, such as the conservation of biodiversity, adaptation to climate change and the emergence of infectious disease. The continued development of research on ER will be necessary if we are to understand the extent to which anthropogenic global change will reduce the Earth's biodiversity.
TL;DR: Toen and Vezzosi as discussed by the authors introduced the notion of n-shifted symplectic structures (n-symplectic structures for short), a generalization of the concept of symplectic structure on smooth varieties and schemes, meaningful in the setting of derived Artin n-stacks.
Abstract: This is the first of a series of papers about quantization in the context of derived algebraic geometry. In this first part, we introduce the notion of n-shifted symplectic structures (n-symplectic structures for short), a generalization of the notion of symplectic structures on smooth varieties and schemes, meaningful in the setting of derived Artin n-stacks (see Toen and Vezzosi in Mem. Am. Math. Soc. 193, 2008 and Toen in Proc. Symp. Pure Math. 80:435–487, 2009). We prove that classifying stacks of reductive groups, as well as the derived stack of perfect complexes, carry canonical 2-symplectic structures. Our main existence theorem states that for any derived Artin stack F equipped with an n-symplectic structure, the derived mapping stack Map(X,F) is equipped with a canonical (n−d)-symplectic structure as soon a X satisfies a Calabi-Yau condition in dimension d. These two results imply the existence of many examples of derived moduli stacks equipped with n-symplectic structures, such as the derived moduli of perfect complexes on Calabi-Yau varieties, or the derived moduli stack of perfect complexes of local systems on a compact and oriented topological manifold. We explain how the known symplectic structures on smooth moduli spaces of simple objects (e.g. simple sheaves on Calabi-Yau surfaces, or simple representations of π1 of compact Riemann surfaces) can be recovered from our results, and that they extend canonically as 0-symplectic structures outside of the smooth locus of simple objects. We also deduce new existence statements, such as the existence of a natural (−1)-symplectic structure (whose formal counterpart has been previously constructed in (Costello, arXiv:1111.4234, 2001) and (Costello and Gwilliam, 2011) on the derived mapping scheme Map(E,T∗X), for E an elliptic curve and T∗X is the total space of the cotangent bundle of a smooth scheme X. Canonical (−1)-symplectic structures are also shown to exist on Lagrangian intersections, on moduli of sheaves (or complexes of sheaves) on Calabi-Yau 3-folds, and on moduli of representations of π1 of compact topological 3-manifolds. More generally, the moduli sheaves on higher dimensional varieties are shown to carry canonical shifted symplectic structures (with a shift depending on the dimension).
TL;DR: Findings provide evidence that BPA congeners and derivatives disrupt multiple NRs and may therefore interfere with the endocrine system, and further research is needed to evaluate the potential endocrine-disrupting activity of putative BPA substitutes.
TL;DR: Deep dermatophytosis appears to be an important clinical manifestation of CARD9 deficiency, and the familial segregation of these alleles was consistent with autosomal recessive inheritance and complete clinical penetrance.
Abstract: Background Deep dermatophytosis is a severe and sometimes life-threatening fungal infection caused by dermatophytes. It is characterized by extensive dermal and subcutaneous tissue invasion and by frequent dissemination to the lymph nodes and, occasionally, the central nervous system. The condition is different from common superficial dermatophyte infection and has been reported in patients with no known immunodeficiency. Patients are mostly from North African, consanguineous, multiplex families, which strongly suggests a mendelian genetic cause. Methods We studied the clinical features of deep dermatophytosis in 17 patients with no known immunodeficiency from eight unrelated Tunisian, Algerian, and Moroccan families. Because CARD9 (caspase recruitment domain–containing protein 9) deficiency has been reported in an Iranian family with invasive fungal infections, we also sequenced CARD9 in the patients. Results Four patients died, at 28, 29, 37, and 39 years of age, with clinically active deep dermatophyto...
TL;DR: It is argued that a major source of this inconsistency is the influence of environmental stressors, which seem capable of revealing, masking, or modulating covariation in physiological and behavioural traits.
Abstract: Although correlations have frequently been observed between specific physiological and behavioural traits across a range of animal taxa, the nature of these associations has been shown to vary. Here we argue that a major source of this inconsistency is the influence of environmental stressors, which seem capable of revealing, masking, or modulating covariation in physiological and behavioural traits. These effects appear to be mediated by changes in the observed variation of traits and differential sensitivity to stressors among phenotypes. Considering that wild animals routinely face a range of biotic and abiotic stressors, increased knowledge of these effects is imperative for understanding the causal mechanisms of a range of ecological phenomena and evolutionary responses to stressors associated with environmental change.
TL;DR: A quantitative Förster resonance energy transfer-based methodology using multiphoton fluorescence lifetime imaging microscopy was developed and found that under homeostatic conditions, the interaction between Keap1 and Nrf2 follows a cycle in which the complex sequentially adopts two distinct conformations.
Abstract: The transcription factor NF-E2 p45-related factor 2 (Nrf2), a master regulator of cytoprotective genes, is controlled by dimeric Kelch-like ECH associated protein 1 (Keap1), a substrate adaptor protein for Cullin3/RING-box protein 1 ubiquitin ligase, which normally targets Nrf2 for ubiquitination and degradation but loses this ability in response to electrophiles and oxidants (inducers). By using recombinant proteins and populations of cells, some of the general features of the regulation of Nrf2 by Keap1 have been outlined. However, how the two proteins interact at a single-cell level is presently unknown. We now report the development of a quantitative Forster resonance energy transfer-based system using multiphoton fluorescence lifetime imaging microscopy and its application for investigating the interaction between Nrf2 and Keap1 in single live cells. By using this approach, we found that under homeostatic conditions, the interaction between Keap1 and Nrf2 follows a cycle in which the complex sequentially adopts two distinct conformations: “open,” in which Nrf2 interacts with a single molecule of Keap1, followed by “closed,” in which Nrf2 binds to both members of the Keap1 dimer. Inducers disrupt this cycle by causing accumulation of the complex in the closed conformation without release of Nrf2. As a consequence, free Keap1 is not regenerated, and newly synthesized Nrf2 is stabilized. On the basis of these findings, we propose a model we have named the “cyclic sequential attachment and regeneration model of Keap1-mediated degradation of Nrf2.” This previously unanticipated dynamism allows rapid transcriptional responses to environmental changes and can accommodate multiple modes of regulation.