Showing papers by "Aix-Marseille University published in 2009"
TL;DR: The Carbohydrate-Active Enzyme (CAZy) database is a knowledge-based resource specialized in the enzymes that build and breakdown complex carbohydrates and glycoconjugates and has been used to improve the quality of functional predictions of a number genome projects by providing expert annotation.
Abstract: The Carbohydrate-Active Enzyme (CAZy) database is a knowledge-based resource specialized in the enzymes that build and breakdown complex carbohydrates and glycoconjugates. As of September 2008, the database describes the present knowledge on 113 glycoside hydrolase, 91 glycosyltransferase, 19 polysaccharide lyase, 15 carbohydrate esterase and 52 carbohydrate-binding module families. These families are created based on experimentally characterized proteins and are populated by sequences from public databases with significant similarity. Protein biochemical information is continuously curated based on the available literature and structural information. Over 6400 proteins have assigned EC numbers and 700 proteins have a PDB structure. The classification (i) reflects the structural features of these enzymes better than their sole substrate specificity, (ii) helps to reveal the evolutionary relationships between these enzymes and (iii) provides a convenient framework to understand mechanistic properties. This resource has been available for over 10 years to the scientific community, contributing to information dissemination and providing a transversal nomenclature to glycobiologists. More recently, this resource has been used to improve the quality of functional predictions of a number genome projects by providing expert annotation. The CAZy resource resides at URL: http://www.cazy.org/.
6,028 citations
University of Gothenburg1, University College Cork2, Paul Scherrer Institute3, Weizmann Institute of Science4, Norwegian Meteorological Institute5, Chalmers University of Technology6, University of Antwerp7, Carnegie Mellon University8, Centre national de la recherche scientifique9, University of Lyon10, University of California, Berkeley11, University of York12, Leibniz Institute for Neurobiology13, University of Mainz14, University of Florida15, University of Colorado Boulder16, Forschungszentrum Jülich17, Ghent University18, University of Manchester19, Aix-Marseille University20, California Institute of Technology21
TL;DR: In this article, an overview of the atmospheric degradation mechanisms for SOA precursors, gas-particle partitioning theory and analytical techniques used to determine the chemical composition of SOA is presented.
Abstract: Secondary organic aerosol (SOA) accounts for a significant fraction of ambient tropospheric aerosol and a detailed knowledge of the formation, properties and transformation of SOA is therefore required to evaluate its impact on atmospheric processes, climate and human health. The chemical and physical processes associated with SOA formation are complex and varied, and, despite considerable progress in recent years, a quantitative and predictive understanding of SOA formation does not exist and therefore represents a major research challenge in atmospheric science. This review begins with an update on the current state of knowledge on the global SOA budget and is followed by an overview of the atmospheric degradation mechanisms for SOA precursors, gas-particle partitioning theory and the analytical techniques used to determine the chemical composition of SOA. A survey of recent laboratory, field and modeling studies is also presented. The following topical and emerging issues are highlighted and discussed in detail: molecular characterization of biogenic SOA constituents, condensed phase reactions and oligomerization, the interaction of atmospheric organic components with sulfuric acid, the chemical and photochemical processing of organics in the atmospheric aqueous phase, aerosol formation from real plant emissions, interaction of atmospheric organic components with water, thermodynamics and mixtures in atmospheric models. Finally, the major challenges ahead in laboratory, field and modeling studies of SOA are discussed and recommendations for future research directions are proposed.
3,324 citations
TL;DR: Key parameters of an RO process and process modifications due to feed water characteristics are brought to light by a direct comparison of seawater and brackish water RO systems.
2,665 citations
Institut Gustave Roussy1, French Institute of Health and Medical Research2, University of Paris-Sud3, Icahn School of Medicine at Mount Sinai4, University of Texas Southwestern Medical Center5, Thomas Jefferson University6, McMaster University7, University of Massachusetts Medical School8, LSU Health Sciences Center New Orleans9, Roswell Park Cancer Institute10, University of Gothenburg11, Boston Children's Hospital12, University of Freiburg13, University of California, San Francisco14, Buck Institute for Research on Aging15, Centre national de la recherche scientifique16, National Institutes of Health17, Technion – Israel Institute of Technology18, University of Leicester19, University of Chieti-Pescara20, Istituto Superiore di Sanità21, University of North Carolina at Chapel Hill22, New York University23, University of Pennsylvania24, Yale University25, Howard Hughes Medical Institute26, University of Ulm27, University of Burgundy28, Aix-Marseille University29, Pasteur Institute30, University of Strasbourg31, Johns Hopkins University32, University of Zurich33, University of Tokyo34, Weizmann Institute of Science35, University of Michigan36, University College London37, Duke University38, University of Graz39, Ghent University40, Trinity College, Dublin41, University of Amsterdam42, University of Lyon43, University of Rome Tor Vergata44, Stony Brook University45, University of Göttingen46, Kyoto University47, Merck & Co.48, Austrian Academy of Sciences49, National University of Singapore50, University of Chicago51, Royal College of Surgeons in Ireland52, La Trobe University53, University of Buenos Aires54, University of Padua55, University of Lisbon56, University of Cambridge57, University of Würzburg58, University of Geneva59, University of Bern60, Rockefeller University61, University of Lausanne62, Osaka University63, University of California, San Diego64, University of Glasgow65, Harvard University66, Karolinska Institutet67
TL;DR: A nonexhaustive comparison of methods to detect cell death with apoptotic or nonapoptotic morphologies, their advantages and pitfalls is provided and the importance of performing multiple, methodologically unrelated assays to quantify dying and dead cells is emphasized.
Abstract: Cell death is essential for a plethora of physiological processes, and its deregulation characterizes numerous human diseases Thus, the in-depth investigation of cell death and its mechanisms constitutes a formidable challenge for fundamental and applied biomedical research, and has tremendous implications for the development of novel therapeutic strategies It is, therefore, of utmost importance to standardize the experimental procedures that identify dying and dead cells in cell cultures and/or in tissues, from model organisms and/or humans, in healthy and/or pathological scenarios Thus far, dozens of methods have been proposed to quantify cell death-related parameters However, no guidelines exist regarding their use and interpretation, and nobody has thoroughly annotated the experimental settings for which each of these techniques is most appropriate Here, we provide a nonexhaustive comparison of methods to detect cell death with apoptotic or nonapoptotic morphologies, their advantages and pitfalls These guidelines are intended for investigators who study cell death, as well as for reviewers who need to constructively critique scientific reports that deal with cellular demise Given the difficulties in determining the exact number of cells that have passed the point-of-no-return of the signaling cascades leading to cell death, we emphasize the importance of performing multiple, methodologically unrelated assays to quantify dying and dead cells
2,218 citations
TL;DR: It is argued that evidence for novel size-dependent properties alone, rather than particle size, should be the primary criterion in any definition of nanoparticles when making decisions about their regulation for environmental, health and safety reasons.
Abstract: The regulation of engineered nanoparticles requires a widely agreed definition of such particles. Nanoparticles are routinely defined as particles with sizes between about 1 and 100 nm that show properties that are not found in bulk samples of the same material. Here we argue that evidence for novel size-dependent properties alone, rather than particle size, should be the primary criterion in any definition of nanoparticles when making decisions about their regulation for environmental, health and safety reasons. We review the size-dependent properties of a variety of inorganic nanoparticles and find that particles larger than about 30 nm do not in general show properties that would require regulatory scrutiny beyond that required for their bulk counterparts.
1,656 citations
TL;DR: It is shown that ALDEFLUOR-positive cells are responsible for mediating metastasis and the hierarchical organization of immortalized cell lines, establish techniques that can facilitate the characterization of regulatory pathways of CSCs, and identify potential stem cell markers and therapeutic targets.
Abstract: Tumors may be initiated and maintained by a cellular subcomponent that displays stem cell properties. We have used the expression of aldehyde dehydrogenase as assessed by the ALDEFLUOR assay to isolate and characterize cancer stem cell (CSC) populations in 33 cell lines derived from normal and malignant mammary tissue. Twenty-three of the 33 cell lines contained an ALDEFLUOR-positive population that displayed stem cell properties in vitro and in NOD/SCID xenografts. Gene expression profiling identified a 413-gene CSC profile that included genes known to play a role in stem cell function, as well as genes such as CXCR1/IL-8RA not previously known to play such a role. Recombinant interleukin-8 (IL-8) increased mammosphere formation and the ALDEFLUOR-positive population in breast cancer cell lines. Finally, we show that ALDEFLUOR-positive cells are responsible for mediating metastasis. These studies confirm the hierarchical organization of immortalized cell lines, establish techniques that can facilitate the characterization of regulatory pathways of CSCs, and identify potential stem cell markers and therapeutic targets.
1,134 citations
TL;DR: In this paper, a detailed analysis of the scientific literature (1993-2007) in order to identify refugia in the Mediterranean region, based on intraspecific phylogeographical studies of plant species, is presented.
Abstract: Aim The aims of this study were to assess the distribution of putative Mediterranean refugia of plants, to compare the locations of refugia and those of regional hotspots of plant biodiversity, and to provide a critical analysis of the Mediterranean refugium paradigm. Furthermore, we consider how biogeographical and genetic results can be combined to guide global conservation strategies. Location The Mediterranean region. Methods We started from a detailed analysis of the scientific literature (1993-2007) in order to identify refugia in the Mediterranean region, based on intraspecific phylogeographical studies of plant species. We used population locations together with gene-pool identity to establish the database, comparing patterns of phylogeographical concordance with the locations of Mediterranean refugia. We then tested the biogeographical congruence between two biodiversity components, namely phylogeographical refugia and regional hotspots. Results We identified 52 refugia in the Mediterranean bioclimatic region and confirmed the role played by the three major peninsulas, with a shared total of 25 refugia. We emphasize the importance of areas that have previously been attributed a lesser role (large Mediterranean islands, North Africa, Turkey, Catalonia). Of the 52 refugia identified, 33 are situated in the western Mediterranean Basin and 19 in the eastern part. The locations of the phylogeographically defined refugia are significantly associated with the 10 regional hotspots of plant biodiversity, with 26 of these refugia (i.e. 50%) occurring within the hotspots. Main conclusions The locations of refugia are determined by complex historical and environmental factors, the cumulative effects of which need to be considered because they have occurred since the Tertiary, rather than solely during the last glacial period. Refugia represent climatically stable areas and constitute a high conservation priority as key areas for the long-term persistence of species and genetic diversity, especially given the threat posed by the extensive environmental change processes operating in the Mediterranean region. The refugia defined here represent 'phylogeographical hotspots'; that is, significant reservoirs of unique genetic diversity favourable to the evolutionary processes of Mediterranean plant species.
968 citations
TL;DR: It is shown that the sponges (Porifera) are monophyletic and not paraphyletic as repeatedly proposed, thus undermining the idea that ancestral metazoans had a sponge-like body plan and that the most likely position for the ctenophores is together with the cnidarians in a "coelenterate" clade.
677 citations
TL;DR: A simplified model of the human gut microbiota illustrates niche specialization and functional redundancy within members of its major bacterial phyla, and the importance of host glycans as a nutrient foundation that ensures ecosystem stability.
Abstract: The adult human distal gut microbial community is typically dominated by 2 bacterial phyla (divisions), the Firmicutes and the Bacteroidetes. Little is known about the factors that govern the interactions between their members. Here, we examine the niches of representatives of both phyla in vivo. Finished genome sequences were generated from Eubacterium rectale and E. eligens, which belong to Clostridium Cluster XIVa, one of the most common gut Firmicute clades. Comparison of these and 25 other gut Firmicutes and Bacteroidetes indicated that the Firmicutes possess smaller genomes and a disproportionately smaller number of glycan-degrading enzymes. Germ-free mice were then colonized with E. rectale and/or a prominent human gut Bacteroidetes, Bacteroides thetaiotaomicron, followed by whole-genome transcriptional profiling, high-resolution proteomic analysis, and biochemical assays of microbial-microbial and microbial-host interactions. B. thetaiotaomicron adapts to E. rectale by up-regulating expression of a variety of polysaccharide utilization loci encoding numerous glycoside hydrolases, and by signaling the host to produce mucosal glycans that it, but not E. rectale, can access. E. rectale adapts to B. thetaiotaomicron by decreasing production of its glycan-degrading enzymes, increasing expression of selected amino acid and sugar transporters, and facilitating glycolysis by reducing levels of NADH, in part via generation of butyrate from acetate, which in turn is used by the gut epithelium. This simplified model of the human gut microbiota illustrates niche specialization and functional redundancy within members of its major bacterial phyla, and the importance of host glycans as a nutrient foundation that ensures ecosystem stability.
670 citations
Woods Hole Oceanographic Institution1, University of California, San Diego2, University of Hawaii3, Academy of Sciences of the Czech Republic4, Sewanee: The University of the South5, Bermuda Institute of Ocean Sciences6, University of Southern Maine7, Aix-Marseille University8, University of Southern California9
TL;DR: It is shown that phytoplankton, in regions of oligotrophic ocean where phosphate is scarce, reduce their cellular phosphorus requirements by substituting non-phosphorus membrane lipids for phospholipids, suggesting that phospholIPid substitutions are fundamental biochemical mechanisms that allow phy toplankon to maintain growth in the face of phosphorus limitation.
Abstract: Phosphorus is an obligate requirement for the growth of all organisms; major biochemical reservoirs of phosphorus in marine plankton include nucleic acids and phospholipids. However, eukaryotic phytoplankton and cyanobacteria (that is, 'phytoplankton' collectively) have the ability to decrease their cellular phosphorus content when phosphorus in their environment is scarce. The biochemical mechanisms that allow phytoplankton to limit their phosphorus demand and still maintain growth are largely unknown. Here we show that phytoplankton, in regions of oligotrophic ocean where phosphate is scarce, reduce their cellular phosphorus requirements by substituting non-phosphorus membrane lipids for phospholipids. In the Sargasso Sea, where phosphate concentrations were less than 10 nmol l-1, we found that only 1.3 +/- 0.6% of phosphate uptake was used for phospholipid synthesis; in contrast, in the South Pacific subtropical gyre, where phosphate was greater than 100 nmol l-1, plankton used 17 6% (ref. 6). Examination of the planktonic membrane lipids at these two locations showed that classes of sulphur- and nitrogen-containing membrane lipids, which are devoid of phosphorus, were more abundant in the Sargasso Sea than in the South Pacific. Furthermore, these non-phosphorus, 'substitute lipids' were dominant in phosphorus-limited cultures of all of the phytoplankton species we examined. In contrast, the marine heterotrophic bacteria we examined contained no substitute lipids and only phospholipids. Thus heterotrophic bacteria, which compete with phytoplankton for nutrients in oligotrophic regions like the Sargasso Sea, appear to have a biochemical phosphorus requirement that phytoplankton avoid by using substitute lipids. Our results suggest that phospholipid substitutions are fundamental biochemical mechanisms that allow phytoplankton to maintain growth in the face of phosphorus limitation.
616 citations
TL;DR: This review summarizes recent findings and outlines important perspectives in this field of reactive oxygen species, which are byproducts of aerobic metabolism and potent agents that cause oxidative damage in cyanobacteria.
Abstract: Reactive oxygen species (ROS) are byproducts of aerobic metabolism and potent agents that cause oxidative damage. In oxygenic photosynthetic organisms such as cyanobacteria, ROS are inevitably generated by photosynthetic electron transport, especially when the intensity of light-driven electron transport outpaces the rate of electron consumption during CO2 fixation. Because cyanobacteria in their natural habitat are often exposed to changing external conditions, such as drastic fluctuations of light intensities, their ability to perceive ROS and to rapidly initiate antioxidant defences is crucial for their survival. This review summarizes recent findings and outlines important perspectives in this field.
TL;DR: Current knowledge on (1)O(2) management in plants and on the biological effects of this peculiar ROS are summarized to indicate that it has a crucial role in the responses of plants to light.
Los Alamos National Laboratory1, University of New Mexico2, Clark University3, Vienna University of Technology4, Spanish National Research Council5, United States Department of Agriculture6, University of Wisconsin-Madison7, United States Department of Energy8, Pontifical Catholic University of Chile9, University of Cincinnati10, Universidad Pública de Navarra11, University of Toronto12, Aix-Marseille University13, Novozymes14, Pacific Northwest National Laboratory15, University of Göttingen16, University of Michigan17, Charles University in Prague18
TL;DR: Comparisons with the closely relatedwhite-rot fungus Phanerochaete chrysosporium support an evolutionary shift from white-rot to brown-rot during which the capacity for efficient depolymerization of lignin was lost.
Abstract: Brown-rot fungi such as Postia placenta are common inhabitants of forest ecosystems and are also largely responsible for the destructive decay of wooden structures. Rapid depolymerization of cellulose is a distinguishing feature of brown-rot, but the biochemical mechanisms and underlying genetics are poorly understood. Systematic examination of the P. placenta genome, transcriptome, and secretome revealed unique extracellular enzyme systems, including an unusual repertoire of extracellular glycoside hydrolases. Genes encoding exocellobiohydrolases and cellulose-binding domains, typical of cellulolytic microbes, are absent in this efficient cellulose-degrading fungus. When P. placenta was grown in medium containing cellulose as sole carbon source, transcripts corresponding to many hemicellulases and to a single putative β-1–4 endoglucanase were expressed at high levels relative to glucose-grown cultures. These transcript profiles were confirmed by direct identification of peptides by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Also up-regulated during growth on cellulose medium were putative iron reductases, quinone reductase, and structurally divergent oxidases potentially involved in extracellular generation of Fe(II) and H2O2. These observations are consistent with a biodegradative role for Fenton chemistry in which Fe(II) and H2O2 react to form hydroxyl radicals, highly reactive oxidants capable of depolymerizing cellulose. The P. placenta genome resources provide unparalleled opportunities for investigating such unusual mechanisms of cellulose conversion. More broadly, the genome offers insight into the diversification of lignocellulose degrading mechanisms in fungi. Comparisons with the closely related white-rot fungus Phanerochaete chrysosporium support an evolutionary shift from white-rot to brown-rot during which the capacity for efficient depolymerization of lignin was lost.
TL;DR: Overall, these data identify fibrillar Aβ as a pathogenic entity powerfully altering neuronal membrane properties such that hyperexcitability of pyramidal cells culminates in epileptiform activity.
Abstract: Alzheimer's disease is associated with an increased risk of unprovoked seizures. However, the underlying mechanisms of seizure induction remain elusive. Here, we performed video-EEG recordings in mice carrying mutant human APPswe and PS1dE9 genes (APdE9 mice) and their wild-type littermates to determine the prevalence of unprovoked seizures. In two recording episodes at the onset of amyloid beta (Abeta) pathogenesis (3 and 4.5 months of age), at least one unprovoked seizure was detected in 65% of APdE9 mice, of which 46% had multiple seizures and 38% had a generalized seizure. None of the wild-type mice had seizures. In a subset of APdE9 mice, seizure phenotype was associated with a loss of calbindin-D28k immunoreactivity in dentate granular cells and ectopic expression of neuropeptide Y in mossy fibers. In APdE9 mice, persistently decreased resting membrane potential in neocortical layer 2/3 pyramidal cells and dentate granule cells underpinned increased network excitability as identified by patch-clamp electrophysiology. At stimulus strengths evoking single-component EPSPs in wild-type littermates, APdE9 mice exhibited decreased action potential threshold and burst firing of pyramidal cells. Bath application (1 h) of Abeta1-42 or Abeta25-35 (proto-)fibrils but not oligomers induced significant membrane depolarization of pyramidal cells and increased the activity of excitatory cell populations as measured by extracellular field recordings in the juvenile rodent brain, confirming the pathogenic significance of bath-applied Abeta (proto-)fibrils. Overall, these data identify fibrillar Abeta as a pathogenic entity powerfully altering neuronal membrane properties such that hyperexcitability of pyramidal cells culminates in epileptiform activity.
TL;DR: Analysis of published data suggests that chemically stable metallic nanoparticles have no significant cellular toxicity, whereas nanoparticles able to be oxidized, reduced or dissolved are cytotoxic and even genotoxic for cellular organisms.
TL;DR: The parameters in greatest need of additional measurements are S(c), mesophyll cell wall thickness, and the permeabilities of the plasma membrane and chloroplast envelope.
Abstract: CO2 faces a series of resistances while diffusing between the substomatal cavities and the sites of carboxylation within chloroplasts. The absence of techniques to measure the resistance of individual steps makes it difficult to define their relative importance. Resistance to diffusion through intercellular airspace differs between leaves, but is usually of minor importance. Leaves with high photosynthetic capacity per unit leaf area reduce mesophyll resistance by increasing the surface area of chloroplasts exposed to intercellular airspace per unit leaf area, Sc. Cell walls impose a significant resistance. Assuming an effective porosity of the cell wall of 0.1 or 0.05, then cell walls could account for 25% or 50% of the total mesophyll resistance, respectively. Since the fraction of apoplastic water that is unbound and available for unhindered CO2 diffusion is unknown, it is possible that the effective porosity is 50% of the total resistance and a variable proportion. Most of the remaining resistance is imposed by one or more of the three membranes as mesophyll resistance can be altered by varying the expression of cooporins. The CO2 permeability of vesicles prepared from chloroplast envelopes has been reduced by RNA interference (RNAi) expression of NtAQP1, but not those prepared from the plasma membrane. Carbonic anhydrase activity also influences mesophyll resistance. Mesophyll resistance is relatively insensitive to the manipulation of any step in the pathway because it represents only part of the total and may also be countered by pleiotropic compensatory changes. The parameters in greatest need of additional measurements are Sc, mesophyll cell wall thickness, and the permeabilities of the plasma membrane and chloroplast envelope.
University of Bremen1, University of Tübingen2, Autonomous University of Barcelona3, University of Kiel4, Oregon State University5, Alfred Wegener Institute for Polar and Marine Research6, Commonwealth Scientific and Industrial Research Organisation7, Aix-Marseille University8, Cardiff University9, Australian National University10, University of Barcelona11, National Taiwan Ocean University12, University of Bordeaux13, Université du Québec à Montréal14, University of Bergen15, University of Cambridge16, University of Limerick17, Newcastle University18, University of Sfax19, Dalhousie University20, University of Liverpool21, Université du Québec22, National Oceanography Centre23, Geoscience Australia24, University of California, Davis25
TL;DR: This article presented an updated synthesis of sea surface temperatures during the Last Glacial Maximum, rigorously defined as the period between 23 and 19 thousand years before present, from the Multiproxy Approach for the Reconstruction of the Glacial Ocean Surface (MARGO) project.
Abstract: Observation-based reconstructions of sea surface temperature from relatively stable periods in the past, such as the Last Glacial Maximum, represent an important means of constraining climate sensitivity and evaluating model simulations1. The first quantitative global reconstruction of sea surface temperatures during the Last Glacial Maximum was developed by the Climate Long-Range Investigation, Mapping and Prediction (CLIMAP) project in the 1970s and 1980s (refs 2, 3). Since that time, several shortcomings of that earlier effort have become apparent4. Here we present an updated synthesis of sea surface temperatures during the Last Glacial Maximum, rigorously defined as the period between 23 and 19 thousand years before present, from the Multiproxy Approach for the Reconstruction of the Glacial Ocean Surface (MARGO) project5. We integrate microfossil and geochemical reconstructions of surface temperatures and include assessments of the reliability of individual records. Our reconstruction reveals the presence of large longitudinal gradients in sea surface temperature in all of the ocean basins, in contrast to the simulations of the Last Glacial Maximum climate available at present6, 7.
TL;DR: Diffraction limited images of living COS-7 cells are presented, with a particular focus on the membrane and organelle dynamics.
Abstract: Phase imaging with a high-resolution wavefront sensor is considered. This is based on a quadriwave lateral shearing interferometer mounted on a non-modified transmission white-light microscope. The measurement technology is explained both in the scope of wave optics and geometrical optics in order to discuss its implementation on a conventional microscope. In particular we consider the effect of a non spatially coherent source on the phase-image signal-to-noise ratio. Precise measurements of the phase-shift introduced by microscopic beads or giant unilamellar vesicles validate the principle and show the accuracy of the methods. Diffraction limited images of living COS-7 cells are then presented, with a particular focus on the membrane and organelle dynamics.
TL;DR: Treatment with golimumab did not demonstrate a favorable risk-benefit profile in this study population of patients with severe persistent asthma, and an unfavorable risk- benefit profile led to early discontinuation of study-agent administration after the Week-24 database lock.
Abstract: Rationale The treatment effect of golimumab, a human monoclonal antibody against tumor necrosis factor (TNF)-alpha, in severe persistent asthma is unknown. Objectives To assess the safety and efficacy of golimumab in a large population of patients with uncontrolled, severe persistent asthma. Methods From 2004 to 2006, 309 patients with severe and uncontrolled asthma, despite high-dose inhaled corticosteroids and long-acting beta(2) agonists, were randomized 1:1:1:1 to monthly subcutaneous injections of placebo or golimumab (50, 100, or 200 mg) through Week 52. Coprimary endpoints were the change from baseline through Week 24 in prebronchodilator percent-predicted FEV(1) and the number of severe asthma exacerbations through Week 24. Measurements and main results No significant differences were observed for the change in percent-predicted FEV1 (least squares mean: placebo, 2.44 [95% confidence interval (CI) -0.574 to 5.461]; combined 100-mg and 200-mg, 2.91 [0.696-5.116]) or severe exacerbations (mean +/- SD: placebo, 0.5 +/- 1.07 vs. combined 100-mg and 200-mg 0.5 +/- 0.97) through week 24. Through Week 24, 2.6% of patients treated with placebo vs. 19.5% of those treated with golimumab discontinued the study agent, and 1.3% and 7.8% discontinued study participation, respectively. An unfavorable risk-benefit profile led to early discontinuation of study-agent administration after the Week-24 database lock. Through Week 76, 20.5% of patients treated with placebo and 30.3% of patients treated with golimumab experienced serious adverse events, with serious infections occurring more frequently in golimumab-treated patients. One death and all eight malignancies occurred in the active groups. Conclusions Overall, treatment with golimumab did not demonstrate a favorable risk-benefit profile in this study population of patients with severe persistent asthma. Clinical trial registered with www.clinicaltrials.gov (NCT00207740).
TL;DR: A design for a cloak to control bending waves propagating in isotropic heterogeneous thin plates is proposed, achieved through homogenization of a multilayered concentric coating filled with piecewise constant isotropIC elastic material.
Abstract: Control of waves with metamaterials is of great topical interest, and is fueled by rapid progress in broadband acoustic and electromagnetic cloaks. We propose a design for a cloak to control bending waves propagating in isotropic heterogeneous thin plates. This is achieved through homogenization of a multilayered concentric coating filled with piecewise constant isotropic elastic material. Significantly, our cloak displays no phase shift for both backward and forward scattering. To foster experimental efforts, we provide a simplified design of the cloak which is shown to work in a more than two-octave frequency range (30 Hz to 150 Hz) when it consists of 10 layers using only 6 different materials overall. This metamaterial should be easy to manufacture, with potential applications ranging from car industry to antiearthquake passive systems for smart buildings, depending upon the plate dimensions and wavelengths.
Harvard University1, University of Arizona2, Duke University3, United States Department of Energy4, Stanford University5, Okayama University6, University of Wisconsin-Madison7, Oregon State University8, Broad Institute9, Institut national de la recherche agronomique10, University of Provence11, Aix-Marseille University12, University of Tennessee Health Science Center13, University of Maryland, College Park14, Purdue University15, University of Amsterdam16, Saint Louis University17, University of Kentucky18, University of Oregon19, Pennsylvania State University20, University of Georgia21
TL;DR: Although the origin(s) of the extra genes and the supernumerary chromosomes is not known, the gene expansion and its large genome size are consistent with this species' diverse range of habitats.
Abstract: The ascomycetous fungus Nectria haematococca, (asexual name Fusarium solani), is a member of a group of .50 species known as the ‘‘Fusarium solani species complex’’. Members of this complex have diverse biological properties including the ability to cause disease on .100 genera of plants and opportunistic infections in humans. The current research analyzed the most extensively studied member of this complex, N. haematococca mating population VI (MPVI). Several genes controlling the ability of individual isolates of this species to colonize specific habitats are located on supernumerary chromosomes. Optical mapping revealed that the sequenced isolate has 17 chromosomes ranging from 530 kb to 6.52 Mb and that the physical size of the genome, 54.43 Mb, and the number of predicted genes, 15,707, are among the largest reported for ascomycetes. Two classes of genes have contributed to gene expansion: specific genes that are not found in other fungi including its closest sequenced relative, Fusarium graminearum; and genes that commonly occur as single copies in other fungi but are present as multiple copies in N. haematococca MPVI. Some of these additional genes appear to have resulted from gene duplication events, while others may have been acquired through horizontal gene transfer. The supernumerary nature of three chromosomes, 14, 15, and 17, was confirmed by their absence in pulsed field gel electrophoresis experiments of some isolates and by demonstrating that these isolates lacked chromosome-specific sequences found on the ends of these chromosomes. These supernumerary chromosomes contain more repeat sequences, are enriched in unique and duplicated genes, and have a lower G+C content in comparison to the other chromosomes. Although the origin(s) of the extra genes and the supernumerary chromosomes is not known, the gene expansion and its large genome size are consistent with this species’ diverse range of habitats. Furthermore, the presence of unique genes on supernumerary chromosomes might account for individual isolates having different environmental niches.
TL;DR: A functional architecture for word recognition that focuses on how orthographic and phonological information cooperates in initial form-based processing of printed word stimuli prior to accessing semantic information is described.
Abstract: We describe a functional architecture for word recognition that focuses on how orthographic and phonological information cooperates in initial form-based processing of printed word stimuli prior to accessing semantic information. Component processes of orthographic processing and orthography-to-phonology translation are described, and the behavioral evidence in favor of such mechanisms is briefly summarized. Our theoretical framework is then used to interpret the results of a large number of recent experiments that have combined the masked priming paradigm with electrophysiological recordings. These experiments revealed a series of components in the event-related potential (ERP), thought to reflect the cascade of underlying processes involved in the transition from visual feature extraction to semantic activation. We provide a tentative mapping of ERP components onto component processes in the model, hence specifying the relative time-course of these processes and their functional significance.
TL;DR: A single velocity, non-conservative hyperbolic model with two energy equations involving relaxation terms is developed that fulfills the equation of state and energy conservation on both sides of interfaces and guarantees correct transmission of shocks across them.
TL;DR: In this paper, it was shown that the raindrops' polydispersity, generically represented according to Marshall-Palmer's law (1948), is quantitatively understood from the fragmentation products of non-interacting, isolated drops.
Abstract: Like many natural objects, raindrops are distributed in size. By extension of what is known to occur inside the clouds, where small droplets grow by accretion of vapour and coalescence, raindrops in the falling rain at the ground level are believed to result from a complex mutual interaction with their neighbours. We show that the raindrops’ polydispersity, generically represented according to Marshall–Palmer’s law (1948), is quantitatively understood from the fragmentation products of non-interacting, isolated drops. Both the shape of the drops’ size distribution, and its parameters are related from first principles to the dynamics of a single drop deforming as it falls in air, ultimately breaking into a dispersion of smaller fragments containing the whole spectrum of sizes observed in rain. The topological change from a big drop into smaller stable fragments—the raindrops—is accomplished within a timescale much shorter than the typical collision time between the drops. The size-distribution profile of raindrops when they reach the ground was previously thought to be governed by complex interactions between neighbouring droplets as they fall. High-speed videos of falling water droplets suggest this is not the case, and that their size distribution can be explained by the fragmentation of individual droplets alone.
TL;DR: Clinical features, overlapping molecular mechanisms, and a specific cognitive mechanism of habit learning that might underlie these behaviours are reviewed and integrated with the emerging view of the basal ganglia as a distributive system involved in the selection and facilitation of movements, acts, and emotions.
Abstract: Dopamine is an essential neurotransmitter for many brain functions, and its dysfunction has been implicated in both neurological and psychiatric disorders. Parkinson's disease is an archetypal disorder of dopamine dysfunction characterised by motor, cognitive, behavioural, and autonomic symptoms. While effective for motor symptoms, dopamine replacement therapy is associated not only with motor side-effects, such as levodopa-induced dyskinesia, but also behavioural side-effects such as impulse control disorders (eg, pathological gambling and shopping, binge eating, and hypersexuality), punding (ie, abnormal repetitive non-goal oriented behaviours), and compulsive medication use. We review clinical features, overlapping molecular mechanisms, and a specific cognitive mechanism of habit learning that might underlie these behaviours. We integrate these mechanisms with the emerging view of the basal ganglia as a distributive system involved in the selection and facilitation of movements, acts, and emotions.
TL;DR: How vitamin D imbalance may lay the foundation for a range of adult disorders, including brain pathologies (Parkinson's disease, epilepsy, depression) and immune-mediated disorders (rheumatoid arthritis, type I diabetes mellitus, systemic lupus erythematosus or inflammatory bowel diseases) is assessed.
TL;DR: The presence of radial and non-radial oscillations in more than 300 giant stars is reported, finding giant stars with equally spaced frequency peaks in the Fourier spectrum of the time series, as well as giants for which the spectrum seems to be more complex.
Abstract: When main-sequence stars like the Sun near the end of their life, they expand to become oscillating red giants. Such evolved stars could in principle provide stringent tests of stellar theory via analysis of radial and non-radial stellar oscillations. Until now it has been unclear whether non-radial modes are observable at all in red giants. De Ridder et al. now report the presence of both radial and non-radial oscillations in over 300 giant stars. For some red giants, mode lifetimes are of the order of a month. Current stellar evolution theory cannot account for these observations. Towards the end of their lives, stars like the Sun expand greatly to become red giant stars that oscillate. Such evolved stars could provide stringent tests of stellar theory through the analysis of radial and non-radial stellar oscillations. Here, the presence of such oscillations in more than 300 giant stars is reported, with mode lifetimes of some of the giants in the order of a month. Towards the end of their lives, stars like the Sun greatly expand to become red giant stars. Such evolved stars could provide stringent tests of stellar theory, as many uncertainties of the internal stellar structure accumulate with age. Important examples are convective overshooting and rotational mixing during the central hydrogen-burning phase, which determine the mass of the helium core, but which are not well understood1. In principle, analysis of radial and non-radial stellar oscillations can be used to constrain the mass of the helium core. Although all giants are expected to oscillate2, it has hitherto been unclear whether non-radial modes are observable at all in red giants, or whether the oscillation modes have a short or a long mode lifetime3,4,5,6,7, which determines the observational precision of the frequencies. Here we report the presence of radial and non-radial oscillations in more than 300 giant stars. For at least some of the giants, the mode lifetimes are of the order of a month. We observe giant stars with equally spaced frequency peaks in the Fourier spectrum of the time series, as well as giants for which the spectrum seems to be more complex. No satisfactory theoretical explanation currently exists for our observations.
TL;DR: In this article, a freeze-dried Si co-precipitated ferrihydite species (Si-ferrihydrite) was used to investigate the effect of Si adsorption on the formation of Fe(III) oxyhydroxides.
TL;DR: O observation of the electroweak production of single top quarks in pp[over ] collisions at sqrt[s]=1.96 TeV based on 2.3 fb(-1) of data collected by the D0 detector at the Fermilab Tevatron Collider is reported.
Abstract: We report observation of the electroweak production of single top quarks in pp collisions at s=1.96 TeV based on 2.3 fb(-1) of data collected by the D0 detector at the Fermilab Tevatron Collider. Using events containing an isolated electron or muon and missing transverse energy, together with jets originating from the fragmentation of b quarks, we measure a cross section of sigma(pp -> tb+X,tqb+X)=3.94 +/- 0.88 pb. The probability to measure a cross section at this value or higher in the absence of signal is 2.5x10(-7), corresponding to a 5.0 standard deviation significance for the observation.
TL;DR: Analysis of gene expression in the colonized cortical cell revealed up-regulation of a lysine motif (LysM)-receptor like kinase, members of the GRAS transcription factor family and a symbiosis-specific ammonium transporter that is a likely candidate for mediating ammonium transport in the AM symbiosis.
Abstract: Most vascular flowering plants have the capacity to form symbiotic associations with arbuscular mycorrhizal (AM) fungi. The symbiosis develops in the roots where AM fungi colonize the root cortex and form arbuscules within the cortical cells. Arbuscules are enveloped in a novel plant membrane and their establishment requires the coordinated cellular activities of both symbiotic partners. The arbuscule-cortical cell interface is the primary functional interface of the symbiosis and is of central importance in nutrient exchange. To determine the molecular events the underlie arbuscule development and function, it is first necessary to identify genes that may play a role in this process. Toward this goal we used the Affymetrix GeneChip® Medicago Genome Array to document the M. truncatula transcript profiles associated with AM symbiosis, and then developed laser microdissection (LM) of M. truncatula root cortical cells to enable analyses of gene expression in individual cell types by RT-PCR. This approach led to the identification of novel M. truncatula and G. intraradices genes expressed in colonized cortical cells and in arbuscules. Within the arbuscule, expression of genes associated with the urea cycle, amino acid biosynthesis and cellular autophagy was detected. Analysis of gene expression in the colonized cortical cell revealed up-regulation of a lysine motif (LysM)-receptor like kinase, members of the GRAS transcription factor family and a symbiosis-specific ammonium transporter that is a likely candidate for mediating ammonium transport in the AM symbiosis. Transcript profiling using the Affymetrix GeneChip® Medicago Genome Array provided new insights into gene expression in M. truncatula roots during AM symbiosis and revealed the existence of several G. intraradices genes on the M. truncatula GeneChip®. A laser microdissection protocol that incorporates low-melting temperature Steedman's wax, was developed to enable laser microdissection of M. truncatula root cortical cells. LM coupled with RT-PCR provided spatial gene expression information for both symbionts and expanded current information available for gene expression in cortical cells containing arbuscules.