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Showing papers by "Pierre-and-Marie-Curie University published in 2009"


Journal ArticleDOI
TL;DR: ClueGO is an easy to use Cytoscape plug-in that strongly improves biological interpretation of large lists of genes and creates a functionally organized GO/pathway term network.
Abstract: We have developed ClueGO, an easy to use Cytoscape plug-in that strongly improves biological interpretation of large lists of genes. ClueGO integrates Gene Ontology (GO) terms as well as KEGG/BioCarta pathways and creates a functionally organized GO/pathway term network. It can analyze one or compare two lists of genes and comprehensively visualizes functionally grouped terms. A one-click update option allows ClueGO to automatically download the most recent GO/KEGG release at any time. ClueGO provides an intuitive representation of the analysis results and can be optionally used in conjunction with the GOlorize plug-in.

4,768 citations


Journal ArticleDOI
TL;DR: In this article, the Lasso estimator and the Dantzig selector exhibit similar behavior under a sparsity scenario, and they derive, in parallel, oracle inequalities for the prediction risk in the general nonparametric regression model, as well as bounds on the l p estimation loss for 1 ≤ p ≤ 2.
Abstract: We show that, under a sparsity scenario, the Lasso estimator and the Dantzig selector exhibit similar behavior. For both methods, we derive, in parallel, oracle inequalities for the prediction risk in the general nonparametric regression model, as well as bounds on the l p estimation loss for 1 ≤ p ≤ 2 in the linear model when the number of variables can be much larger than the sample size.

2,524 citations


Journal ArticleDOI
19 Jun 2009-Immunity
TL;DR: The dissection of FoxP3(+) cells into subsets enables one to analyze Treg cell differentiation dynamics and interactions in normal and disease states, and to control immune responses through manipulating particular FoxP 3(+) subpopulations.

1,979 citations


Journal ArticleDOI
TL;DR: In the past 50 years, the fraction of CO2 emissions that remains in the atmosphere each year has likely increased, from about 40% to 45%, and models suggest that this trend was caused by a decrease in the uptake of CO 2 by the carbon sinks in response to climate change and variability as mentioned in this paper.
Abstract: Efforts to control climate change require the stabilization of atmospheric CO2 concentrations. This can only be achieved through a drastic reduction of global CO2 emissions. Yet fossil fuel emissions increased by 29% between 2000 and 2008, in conjunction with increased contributions from emerging economies, from the production and international trade of goods and services, and from the use of coal as a fuel source. In contrast, emissions from land-use changes were nearly constant. Between 1959 and 2008, 43% of each year's CO2 emissions remained in the atmosphere on average; the rest was absorbed by carbon sinks on land and in the oceans. In the past 50 years, the fraction of CO2 emissions that remains in the atmosphere each year has likely increased, from about 40% to 45%, and models suggest that this trend was caused by a decrease in the uptake of CO2 by the carbon sinks in response to climate change and variability. Changes in the CO2 sinks are highly uncertain, but they could have a significant influence on future atmospheric CO2 levels. It is therefore crucial to reduce the uncertainties.

1,909 citations


Journal ArticleDOI
TL;DR: In this article, a global mean distribution for surface water pCO2 over the global oceans in non-El Nino conditions has been constructed with spatial resolution of 4° (latitude) × 5° (longitude) for a reference year 2000 based upon about 3 million measurements of surface water PCO2 obtained from 1970 to 2007.
Abstract: A climatological mean distribution for the surface water pCO2 over the global oceans in non-El Nino conditions has been constructed with spatial resolution of 4° (latitude) ×5° (longitude) for a reference year 2000 based upon about 3 million measurements of surface water pCO2 obtained from 1970 to 2007. The database used for this study is about 3 times larger than the 0.94 million used for our earlier paper [Takahashi et al., 2002. Global sea–air CO2 flux based on climatological surface ocean pCO2, and seasonal biological and temperature effects. Deep-Sea Res. II, 49, 1601–1622]. A time-trend analysis using deseasonalized surface water pCO2 data in portions of the North Atlantic, North and South Pacific and Southern Oceans (which cover about 27% of the global ocean areas) indicates that the surface water pCO2 over these oceanic areas has increased on average at a mean rate of 1.5 μatm y−1 with basin-specific rates varying between 1.2±0.5 and 2.1±0.4 μatm y−1. A global ocean database for a single reference year 2000 is assembled using this mean rate for correcting observations made in different years to the reference year. The observations made during El Nino periods in the equatorial Pacific and those made in coastal zones are excluded from the database. Seasonal changes in the surface water pCO2 and the sea-air pCO2 difference over four climatic zones in the Atlantic, Pacific, Indian and Southern Oceans are presented. Over the Southern Ocean seasonal ice zone, the seasonality is complex. Although it cannot be thoroughly documented due to the limited extent of observations, seasonal changes in pCO2 are approximated by using the data for under-ice waters during austral winter and those for the marginal ice and ice-free zones. The net air–sea CO2 flux is estimated using the sea–air pCO2 difference and the air–sea gas transfer rate that is parameterized as a function of (wind speed)2 with a scaling factor of 0.26. This is estimated by inverting the bomb 14C data using Ocean General Circulation models and the 1979–2005 NCEP-DOE AMIP-II Reanalysis (R-2) wind speed data. The equatorial Pacific (14°N–14°S) is the major source for atmospheric CO2, emitting about +0.48 Pg-C y−1, and the temperate oceans between 14° and 50° in the both hemispheres are the major sink zones with an uptake flux of −0.70 Pg-C y−1 for the northern and −1.05 Pg-C y−1 for the southern zone. The high-latitude North Atlantic, including the Nordic Seas and portion of the Arctic Sea, is the most intense CO2 sink area on the basis of per unit area, with a mean of −2.5 tons-C month−1 km−2. This is due to the combination of the low pCO2 in seawater and high gas exchange rates. In the ice-free zone of the Southern Ocean (50°–62°S), the mean annual flux is small (−0.06 Pg-C y−1) because of a cancellation of the summer uptake CO2 flux with the winter release of CO2 caused by deepwater upwelling. The annual mean for the contemporary net CO2 uptake flux over the global oceans is estimated to be −1.6±0.9 Pg-C y−1, which includes an undersampling correction to the direct estimate of −1.4±0.7 Pg-C y−1. Taking the pre-industrial steady-state ocean source of 0.4±0.2 Pg-C y−1 into account, the total ocean uptake flux including the anthropogenic CO2 is estimated to be −2.0±1.0 Pg-C y−1 in 2000.

1,653 citations


Journal ArticleDOI
TL;DR: Among patients with an acute myocardial infarction who were receiving clopidogrel, those carrying CYP2C19 loss-of-function alleles had a higher rate of subsequent cardiovascular events than those who were not, particularly marked among the patients undergoing percutaneous coronary intervention.
Abstract: Background Pharmacogenetic determinants of the response of patients to clopidogrel contribute to variability in the biologic antiplatelet activity of the drug. The effect of these determinants on clinical outcomes after an acute myocardial infarction is unknown. Methods We consecutively enrolled 2208 patients presenting with an acute myocardial infarction in a nationwide French registry and receiving clopidogrel therapy. We then assessed the relation of allelic variants of genes modulating clopidogrel absorption (ABCB1), metabolic activation (CYP3A5 and CYP2C19), and biologic activity (P2RY12 and ITGB3) to the risk of death from any cause, nonfatal stroke, or myocardial infarction during 1 year of follow-up. Results Death occurred in 225 patients, and nonfatal myocardial infarction or stroke in 94 patients, during the follow-up period. None of the selected single-nucleotide polymorphisms (SNPs) in CYP3A5, P2RY12, or ITGB3 were associated with a risk of an adverse outcome. Patients with two variant alleles of ABCB1 (TT at nucleotide 3435) had a higher rate of cardiovascular events at 1 year than those with the ABCB1 wild-type genotype (CC at nucleotide 3435) (15.5% vs. 10.7%; adjusted hazard ratio, 1.72; 95% confidence interval [CI], 1.20 to 2.47). Patients carrying any two CYP2C19 loss-offunction alleles (*2, *3, *4, or *5), had a higher event rate than patients with none (21.5% vs. 13.3%; adjusted hazard ratio, 1.98; 95% CI, 1.10 to 3.58). Among the 1535 patients who underwent percutaneous coronary intervention during hospitalization, the rate of cardiovascular events among patients with two CYP2C19 loss-of-function alleles was 3.58 times the rate among those with none (95% CI, 1.71 to 7.51). Conclusions Among patients with an acute myocardial infarction who were receiving clo pid ogrel, those carrying CYP2C19 loss-of-function alleles had a higher rate of subsequent cardiovascular events than those who were not. This effect was particularly marked among the patients undergoing percutaneous coronary intervention. (ClinicalTrials. gov number, NCT00673036.)

1,623 citations


Journal ArticleDOI
TL;DR: Although the data are inconclusive about any possible effect on myocardial infarction, rosiglitazone does not increase the risk of overall cardiovascular morbidity or mortality compared with standard glucose-lowering drugs.

1,308 citations


Journal ArticleDOI
TL;DR: An important adaptive role for metabolism diversification within group B2 and Shigella strains is found, but few or no extraint intestinal virulence-specific genes are identified, which could render difficult the development of a vaccine against extraintestinal infections.
Abstract: The Escherichia coli species represents one of the best-studied model organisms, but also encompasses a variety of commensal and pathogenic strains that diversify by high rates of genetic change. We uniformly (re-) annotated the genomes of 20 commensal and pathogenic E. coli strains and one strain of E. fergusonii (the closest E. coli related species), including seven that we sequenced to completion. Within the approximately 18,000 families of orthologous genes, we found approximately 2,000 common to all strains. Although recombination rates are much higher than mutation rates, we show, both theoretically and using phylogenetic inference, that this does not obscure the phylogenetic signal, which places the B2 phylogenetic group and one group D strain at the basal position. Based on this phylogeny, we inferred past evolutionary events of gain and loss of genes, identifying functional classes under opposite selection pressures. We found an important adaptive role for metabolism diversification within group B2 and Shigella strains, but identified few or no extraintestinal virulence-specific genes, which could render difficult the development of a vaccine against extraintestinal infections. Genome flux in E. coli is confined to a small number of conserved positions in the chromosome, which most often are not associated with integrases or tRNA genes. Core genes flanking some of these regions show higher rates of recombination, suggesting that a gene, once acquired by a strain, spreads within the species by homologous recombination at the flanking genes. Finally, the genome's long-scale structure of recombination indicates lower recombination rates, but not higher mutation rates, at the terminus of replication. The ensuing effect of background selection and biased gene conversion may thus explain why this region is A+T-rich and shows high sequence divergence but low sequence polymorphism. Overall, despite a very high gene flow, genes co-exist in an organised genome.

1,213 citations


Journal ArticleDOI
TL;DR: The fecal microbiota of patients with IBD differs from that of healthy subjects, and the phylum Firmicutes and particularly the species F. prausnitzii, are underrepresented in A‐IBD patients as well as in IC patients, which could be crucial to gut homeostasis.
Abstract: Background: The intestinal microbiota is suspected to play a role in colitis and particularly in inflammatory bowel disease (IBD) pathogenesis. The aim was to compare the fecal microbiota composition of patients with colitis to that of healthy subjects (HS). Methods: fecal samples from 22 active Crohn's disease (A-CD) patients, 10 CD patients in remission (R-CD), 13 active ulcerative colitis (A-UC) patients, 4 UC patients in remission (R-UC), 8 infectious colitis (IC) patients, and 27 HS were analyzed by quantitative real-time polymerase chain reaction (PCR) targeting the 16S rRNA gene. Bacterial counts were transformed to logarithms (Log10 CFU) for statistical analysis. Results: Bacteria of the phylum Firmicutes (Clostridium leptum and Clostridium coccoides groups) were less represented in A-IBD patients (9.7; P = 0.004) and IC (9.4; P = 0.02), compared to HS (10.8). Faecalibacterium prausnitzii species (a major representative of the C. leptum group) had lower counts in A-IBD and IC patients compared to HS (8.8 and 8.3 versus 10.4; P = 0.0004 and P = 0.003). The Firmicutes/Bacteroidetes ratio was lower in A-IBD (1.3; P = 0.0001) and IC patients (0.4; P = 0.002). Compared to HS, Bifidobacteria were less represented in A-IBD and IC (7.9 and 7.7 versus 9.2; P = 0.001 and P = 0.01). Conclusions: The fecal microbiota of patients with IBD differs from that of HS. The phylum Firmicutes and particularly the species F. prausnitzii, are underrepresented in A-IBD patients as well as in IC patients. These bacteria could be crucial to gut homeostasis since lower counts of F. prausnitzii are consistently associated with a reduced protection of the gut mucosa. (Inflamm Bowel Dis 2009)

1,123 citations


Journal ArticleDOI
TL;DR: Recent literature providing strong evidence that individual variation in dispersal has an important impact on both reinforcement and colonization success and therefore must be taken into account when predicting ecological responses to global warming and habitat fragmentation is discussed.
Abstract: There is accumulating evidence that individuals leave their natal area and select a breeding habitat non-randomly by relying upon information about their natal and future breeding environments. This variation in dispersal is not only based on external information (condition dependence) but also depends upon the internal state of individuals (phenotype dependence). As a consequence, not all dispersers are of the same quality or search for the same habitats. In addition, the individual's state is characterized by morphological, physiological or behavioural attributes that might themselves serve as a cue altering the habitat choice of conspecifics. These combined effects of internal and external information have the potential to generate complex movement patterns and could influence population dynamics and colonization processes. Here, we highlight three particular processes that link condition-dependent dispersal, phenotype-dependent dispersal and habitat choice strategies: (1) the relationship between the cause of departure and the dispersers' phenotype; (2) the relationship between the cause of departure and the settlement behaviour and (3) the concept of informed dispersal, where individuals gather and transfer information before and during their movements through the landscape. We review the empirical evidence for these processes with a special emphasis on vertebrate and arthropod model systems, and present case studies that have quantified the impacts of these processes on spatially structured population dynamics. We also discuss recent literature providing strong evidence that individual variation in dispersal has an important impact on both reinforcement and colonization success and therefore must be taken into account when predicting ecological responses to global warming and habitat fragmentation.

1,061 citations


Journal ArticleDOI
TL;DR: In this paper, it was shown that the near-horizon quantum states can be identified with those of (a chiral half of) a two-dimensional conformal field theory (CFT), and the results apply to any consistent unitary quantum theory of gravity with a Kerr solution.
Abstract: Quantum gravity in the region very near the horizon of an extreme Kerr black hole (whose angular momentum and mass are related by J=GM^2) is considered. It is shown that consistent boundary conditions exist, for which the asymptotic symmetry generators form one copy of the Virasoro algebra with central charge c_L=12J / \hbar. This implies that the near-horizon quantum states can be identified with those of (a chiral half of) a two-dimensional conformal field theory (CFT). Moreover, in the extreme limit, the Frolov-Thorne vacuum state reduces to a thermal density matrix with dimensionless temperature T_L=1/2\pi and conjugate energy given by the zero mode generator, L_0, of the Virasoro algebra. Assuming unitarity, the Cardy formula then gives a microscopic entropy S_{micro}=2\pi J / \hbar for the CFT, which reproduces the macroscopic Bekenstein-Hawking entropy S_{macro}=Area / 4\hbar G. The results apply to any consistent unitary quantum theory of gravity with a Kerr solution. We accordingly conjecture that extreme Kerr black holes are holographically dual to a chiral two-dimensional conformal field theory with central charge c_L=12J / \hbar, and in particular that the near-extreme black hole GRS 1915+105 is approximately dual to a CFT with c_L \sim 2 \times 10^{79}.

Journal ArticleDOI
TL;DR: Patients receiving thiopurines for inflammatory bowel disease have an increased risk of developing lymphoproliferative disorders, and most cases associated withThiopurine exposure matched the pathological range of post-transplant disease.

Journal ArticleDOI
TL;DR: The road is now open to address individual molecules wired to a conducting surface in their blocked magnetization state, thereby enabling investigation of the elementary interactions between electron transport and magnetism degrees of freedom at the molecular scale.
Abstract: In the field of molecular spintronics, the use of magnetic molecules for information technology is a main target and the observation of magnetic hysteresis on individual molecules organized on surfaces is a necessary step to develop molecular memory arrays. Although simple paramagnetic molecules can show surface-induced magnetic ordering and hysteresis when deposited on ferromagnetic surfaces, information storage at the molecular level requires molecules exhibiting an intrinsic remnant magnetization, like the so-called single-molecule magnets (SMMs). These have been intensively investigated for their rich quantum behaviour but no magnetic hysteresis has been so far reported for monolayers of SMMs on various non-magnetic substrates, most probably owing to the chemical instability of clusters on surfaces. Using X-ray absorption spectroscopy and X-ray magnetic circular dichroism synchrotron-based techniques, pushed to the limits in sensitivity and operated at sub-kelvin temperatures, we have now found that robust, tailor-made Fe(4) complexes retain magnetic hysteresis at gold surfaces. Our results demonstrate that isolated SMMs can be used for storing information. The road is now open to address individual molecules wired to a conducting surface in their blocked magnetization state, thereby enabling investigation of the elementary interactions between electron transport and magnetism degrees of freedom at the molecular scale.

Journal ArticleDOI
TL;DR: The results suggest that the most phylogenetically recent part of the cerebellum, particularly crus I and II, make contributions to parallel cortico-cerebellar loops involved in executive control, salience detection, and episodic memory/self-reflection.
Abstract: Convergent data from various scientific approaches strongly implicate cerebellar systems in nonmotor functions. The functional anatomy of these systems has been pieced together from disparate sources, such as animal studies, lesion studies in humans, and structural and functional imaging studies in humans. To better define this distinct functional anatomy, in the current study we delineate the role of the cerebellum in several nonmotor systems simultaneously and in the same subjects using resting state functional connectivity MRI. Independent component analysis was applied to resting state data from two independent datasets to identify common cerebellar contributions to several previously identified intrinsic connectivity networks (ICNs) involved in executive control, episodic memory/self-reflection, salience detection, and sensorimotor function. We found distinct cerebellar contributions to each of these ICNs. The neocerebellum participates in (1) the right and left executive control networks (especially crus I and II), (2) the salience network (lobule VI), and (3) the default-mode network (lobule IX). Little to no overlap was detected between these cerebellar regions and the sensorimotor cerebellum (lobules V-VI). Clusters were also located in pontine and dentate nuclei, prominent points of convergence for cerebellar input and output, respectively. The results suggest that the most phylogenetically recent part of the cerebellum, particularly crus I and II, make contributions to parallel cortico-cerebellar loops involved in executive control, salience detection, and episodic memory/self-reflection. The largest portions of the neocerebellum take part in the executive control network implicated in higher cognitive functions such as working memory.

Journal ArticleDOI
TL;DR: In this article, the existence of superfluidity in polaritons is investigated in terms of the Landau criterion and manifests itself as the suppression of scattering from defects when the flow velocity is slower than the speed of sound in the fluid.
Abstract: Similar to atoms in cold gases, exciton–polaritons in semiconductor microcavities can undergo Bose–Einstein condensation. A striking consequence of the appearance of macroscopic coherence in these systems is superfluidity. Now, clear evidence for such behaviour has been found in an exciton–polariton condensate. Superfluidity, the ability of a quantum fluid to flow without friction, is one of the most spectacular phenomena occurring in degenerate gases of interacting bosons. Since its first discovery in liquid helium-4 (refs 1, 2), superfluidity has been observed in quite different systems, and recent experiments with ultracold trapped atoms have explored the subtle links between superfluidity and Bose–Einstein condensation3,4,5. In solid-state systems, it has been anticipated that exciton–polaritons in semiconductor microcavities should behave as an unusual quantum fluid6,7,8, with unique properties stemming from its intrinsically non-equilibrium nature. This has stimulated the quest for an experimental demonstration of superfluidity effects in polariton systems9,10,11,12,13. Here, we report clear evidence for superfluid motion of polaritons. Superfluidity is investigated in terms of the Landau criterion and manifests itself as the suppression of scattering from defects when the flow velocity is slower than the speed of sound in the fluid. Moreover, a Cerenkov-like wake pattern is observed when the flow velocity exceeds the speed of sound. The experimental findings are in quantitative agreement with predictions based on a generalized Gross–Pitaevskii theory12,13, and establish microcavity polaritons as a system for exploring the rich physics of non-equilibrium quantum fluids.

Journal ArticleDOI
TL;DR: It is argued that the trade‐off hypothesis and its basic extensions are necessary to assess the qualitative impacts of virulence management strategies and many processes such as pathogen adaptation to within‐host competition, interactions with the immune system and shifting transmission routes, will all be interrelated making sweeping evolutionary predictions harder to obtain.
Abstract: It has been more than two decades since the formulation of the so-called ‘trade-off’ hypothesis as an alternative to the then commonly accepted idea that parasites should always evolve towards avirulence (the ‘avirulence hypothesis’). The trade-off hypothesis states that virulence is an unavoidable consequence of parasite transmission; however, since the 1990s, this hypothesis has been increasingly challenged. We discuss the history of the study of virulence evolution and the development of theories towards the trade-off hypothesis in order to illustrate the context of the debate. We investigate the arguments raised against the trade-off hypothesis and argue that trade-offs exist, but may not be of the simple form that is usually assumed, involving other mechanisms (and life-history traits) than those originally considered. Many processes such as pathogen adaptation to within-host competition, interactions with the immune system and shifting transmission routes, will all be interrelated making sweeping evolutionary predictions harder to obtain. We argue that this is the heart of the current debate in the field and while species-specific models may be better predictive tools, the trade-off hypothesis and its basic extensions are necessary to assess the qualitative impacts of virulence management strategies.

Journal ArticleDOI
TL;DR: A review of the GISAXS technique, from experimental issues to the theories underlying the data analysis, with a wealth of examples, can be found in this paper, where the authors introduce the notions of particle form factor and interference function, together with the different cases encountered according to the size/shape dispersion.

Journal ArticleDOI
27 Aug 2009-Nature
TL;DR: It is shown that the surface layer on the dormant conidia masks their recognition by the immune system and hence prevents immune response, and also immunologically silences airborne moulds.
Abstract: The air we breathe is filled with thousands of fungal spores (conidia) per cubic metre, which in certain composting environments can easily exceed 10(9) per cubic metre. They originate from more than a hundred fungal species belonging mainly to the genera Cladosporium, Penicillium, Alternaria and Aspergillus. Although these conidia contain many antigens and allergens, it is not known why airborne fungal microflora do not activate the host innate immune cells continuously and do not induce detrimental inflammatory responses following their inhalation. Here we show that the surface layer on the dormant conidia masks their recognition by the immune system and hence prevents immune response. To explore this, we used several fungal members of the airborne microflora, including the human opportunistic fungal pathogen Aspergillus fumigatus, in in vitro assays with dendritic cells and alveolar macrophages and in in vivo murine experiments. In A. fumigatus, this surface 'rodlet layer' is composed of hydrophobic RodA protein covalently bound to the conidial cell wall through glycosylphosphatidylinositol-remnants. RodA extracted from conidia of A. fumigatus was immunologically inert and did not induce dendritic cell or alveolar macrophage maturation and activation, and failed to activate helper T-cell immune responses in vivo. The removal of this surface 'rodlet/hydrophobin layer' either chemically (using hydrofluoric acid), genetically (DeltarodA mutant) or biologically (germination) resulted in conidial morphotypes inducing immune activation. All these observations show that the hydrophobic rodlet layer on the conidial cell surface immunologically silences airborne moulds.

Journal ArticleDOI
TL;DR: Patients with APS still develop significant morbidity and mortality despite current treatment, and it is imperative to increase the efforts in determining optimal prognostic markers and therapeutic measures to prevent these complications.
Abstract: Objectives: To identify the main causes of morbidity and mortality in patients with antiphospholipid syndrome (APS) during a 5-year period and to determine clinical and immunological parameters with prognostic significance. Methods: The clinical and immunological features of a cohort of 1000 patients with APS from 13 European countries who had been followed up from 1999 to 2004 were analysed. Results: 200 (20%) patients developed APS-related manifestations during the 5-year study period. Recurrent thrombotic events appeared in 166 (16.6%) patients and the most common were strokes (2.4% of the total cohort), transient ischaemic attacks (2.3%), deep vein thromboses (2.1%) and pulmonary embolism (2.1%). When the thrombotic events occurred, 90 patients were receiving oral anticoagulants and 49 were using aspirin. 31/420 (7.4%) patients receiving oral anticoagulants presented with haemorrhage. 3/121 (2.5%) women with only obstetric APS manifestations at the start of the study developed a new thrombotic event. A total of 77 women (9.4% of the female patients) had one or more pregnancies and 63 (81.8% of pregnant patients) had one or more live births. The most common fetal complications were early pregnancy loss (17.1% of pregnancies) and premature birth (35% of live births). 53 (5.3% of the total cohort) patients died. The most common causes of death were bacterial infection (21% of deaths), myocardial infarction (19%) and stroke (13%). No clinical or immunological predictor of thrombotic events, pregnancy morbidity or mortality was detected. Conclusion: Patients with APS still develop significant morbidity and mortality despite current treatment (oral anticoagulants or antiaggregants, or both).

Journal ArticleDOI
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.

Journal ArticleDOI
27 Oct 2009-BMJ
TL;DR: Migraine is associated with a twofold increased risk of ischaemic stroke, which is only apparent among people who have migraine with aura, and the results suggest a higher risk among women and risk was further magnified for people with migraine who were aged less than 45, smokers, and women who used oral contraceptives.
Abstract: Objective To evaluate the association between migraine and cardiovascular disease, including stroke, myocardial infarction, and death due to cardiovascular disease. Design Systematic review and meta-analysis. Data sources Electronic databases (PubMed, Embase, Cochrane Library) and reference lists of included studies and reviews published until January 2009. Selection criteria Case-control and cohort studies investigating the association between any migraine or specific migraine subtypes and cardiovascular disease. Review methods Two investigators independently assessed eligibility of identified studies in a two step approach. Disagreements were resolved by consensus. Studies were grouped according to a priori categories on migraine and cardiovascular disease. Data extraction Two investigators extracted data. Pooled relative risks and 95% confidence intervals were calculated. Results Studies were heterogeneous for participant characteristics and definition of cardiovascular disease. Nine studies investigated the association between any migraine and ischaemic stroke (pooled relative risk 1.73, 95% confidence interval 1.31 to 2.29). Additional analyses indicated a significantly higher risk among people who had migraine with aura (2.16, 1.53 to 3.03) compared with people who had migraine without aura (1.23, 0.90 to 1.69; meta-regression for aura status P=0.02). Furthermore, results suggested a greater risk among women (2.08, 1.13 to 3.84) compared with men (1.37, 0.89 to 2.11). Age less than 45 years, smoking, and oral contraceptive use further increased the risk. Eight studies investigated the association between migraine and myocardial infarction (1.12, 0.95 to 1.32) and five between migraine and death due to cardiovascular disease (1.03, 0.79 to 1.34). Only one study investigated the association between women who had migraine with aura and myocardial infarction and death due to cardiovascular disease, showing a twofold increased risk. Conclusion Migraine is associated with a twofold increased risk of ischaemic stroke, which is only apparent among people who have migraine with aura. Our results also suggest a higher risk among women and risk was further magnified for people with migraine who were aged less than 45, smokers, and women who used oral contraceptives. We did not find an overall association between any migraine and myocardial infarction or death due to cardiovascular disease. Too few studies are available to reliably evaluate the impact of modifying factors, such as migraine aura, on these associations.

Journal ArticleDOI
TL;DR: In this paper, a point-like signal is detected at a projected distance of 8 AU from the star, within the northeastern extension of the dust disk, which suggests a formation process by core accretion or disk instabilities rather than binary-like formation processes.
Abstract: Context. Since the discovery of its dusty disk in 1984, β Pictoris has become the prototype of young early-type planetary systems, and there are now various indications that a massive Jovian planet is orbiting the star at ∼10 AU. However, no planets have been detected around this star so far. Aims. Our goal was to investigate the close environment of β Pic, searching for planetary companion(s). Methods. Deep adaptive-optics L � -band images of β Pic were recorded using the NaCo instrument at the Very Large Telescope. Results. A faint point-like signal is detected at a projected distance of � 8 AU from the star, within the northeastern extension of the dust disk. Various tests were made to rule out possible instrumental or atmospheric artefacts at a good confidence level. The probability of a foreground or background contaminant is extremely low, based in addition on the analysis of previous deep HST images. Its L � = 11.2 apparent magnitude would indicate a typical temperature of ∼1500 K and a mass of ∼8 MJup. If confirmed, it could explain the main morphological and dynamical peculiarities of the β Pic system. The present detection is unique among A-stars by the proximity of the resolved planet to its parent star. Its closeness and location inside the β Pic disk suggest a formation process by core accretion or disk instabilities rather than binary-like formation processes.

Journal ArticleDOI
TL;DR: In this paper, the spatial and temporal variability of these inputs since the early 1960s, based on a review of available data on water discharge, nutrient concentrations and climatic parameters, is presented.

Journal ArticleDOI
10 Apr 2009-Science
TL;DR: It is found that genomes from two isolates shared only 90% of their predicted genes, and divergence appears to have been facilitated by selection and acquisition processes that actively shape the repertoire of genes that are mutually exclusive between the two isolate differently than the core genes.
Abstract: Picoeukaryotes are a taxonomically diverse group of organisms less than 2 micrometers in diameter. Photosynthetic marine picoeukaryotes in the genus Micromonas thrive in ecosystems ranging from tropical to polar and could serve as sentinel organisms for biogeochemical fluxes of modern oceans during climate change. These broadly distributed primary producers belong to an anciently diverged sister clade to land plants. Although Micromonas isolates have high 18S ribosomal RNA gene identity, we found that genomes from two isolates shared only 90% of their predicted genes. Their independent evolutionary paths were emphasized by distinct riboswitch arrangements as well as the discovery of intronic repeat elements in one isolate, and in metagenomic data, but not in other genomes. Divergence appears to have been facilitated by selection and acquisition processes that actively shape the repertoire of genes that are mutually exclusive between the two isolates differently than the core genes. Analyses of the Micromonas genomes offer valuable insights into ecological differentiation and the dynamic nature of early plant evolution.

Journal ArticleDOI
TL;DR: An auditory paradigm that evaluates cerebral responses to violations of temporal regularities that are either local in time or global across several seconds suggests that the presence of the global effect is a signature of conscious processing, although it can be absent in conscious subjects who are not aware of theglobal auditory regularities.
Abstract: Can conscious processing be inferred from neurophysiological measurements? Some models stipulate that the active maintenance of perceptual representations across time requires consciousness. Capitalizing on this assumption, we designed an auditory paradigm that evaluates cerebral responses to violations of temporal regularities that are either local in time or global across several seconds. Local violations led to an early response in auditory cortex, independent of attention or the presence of a concurrent visual task, whereas global violations led to a late and spatially distributed response that was only present when subjects were attentive and aware of the violations. We could detect the global effect in individual subjects using functional MRI and both scalp and intracerebral event-related potentials. Recordings from 8 noncommunicating patients with disorders of consciousness confirmed that only conscious individuals presented a global effect. Taken together these observations suggest that the presence of the global effect is a signature of conscious processing, although it can be absent in conscious subjects who are not aware of the global auditory regularities. This simple electrophysiological marker could thus serve as a useful clinical tool.

Journal ArticleDOI
TL;DR: Losartan 150 mg daily reduced the rate of death or admission for heart failure in patients with heart failure, reduced left-ventricular ejection fraction, and intolerance to ACE inhibitors compared with losartan 50 mg daily, and shows the value of up-titrating ARB doses to confer clinical benefit.

Journal ArticleDOI
TL;DR: In this article, a generalized pre-averaging approach for estimating the integrated volatility is presented, which can generate rate optimal estimators with convergence rate n 1/4. But the convergence rate is not guaranteed.

Journal ArticleDOI
07 Aug 2009-Cell
TL;DR: This cycle of neogenesis and redifferentiation caused by ectopic expression of Pax4 in alpha cells is capable of restoring a functional beta cell mass and curing diabetes in animals that have been chemically depleted of beta cells.

Journal ArticleDOI
06 Feb 2009-Science
TL;DR: The genetic basis of evolution may be predictable to some extent, and further understanding of this predictability requires incorporation of the specific functions and characteristics of genes into evolutionary theory.
Abstract: Ever since the integration of Mendelian genetics into evolutionary biology in the early 20th century, evolutionary geneticists have for the most part treated genes and mutations as generic entities. However, recent observations indicate that all genes are not equal in the eyes of evolution. Evolutionarily relevant mutations tend to accumulate in hotspot genes and at specific positions within genes. Genetic evolution is constrained by gene function, the structure of genetic networks, and population biology. The genetic basis of evolution may be predictable to some extent, and further understanding of this predictability requires incorporation of the specific functions and characteristics of genes into evolutionary theory.

Book ChapterDOI
TL;DR: This review has focused on the genetic and signalling pathways activated early after cold exposure, and particularly on the MAP-kinase module, which has been shown to be involved in the cold response.
Abstract: Exposure to low temperatures is one of the most important plant abiotic stress factors. In this review we describe the damages that chilling and/or freezing temperatures can cause to plant cells. Confronted to these damages, some plants are able to adapt through mechanisms based on protein synthesis, membrane composition changes, and activation of active oxygen scavenging systems. These adaptive mechanisms rely in part on gene induction. The best understood genetic pathway leading to gene induction upon a temperature downshift is based on C-repeat-binding factors (CBF) activating promoters through the C-repeat (CRT) cis-element. Such activation of transcription factors suggests that cold, as a signal, has been transduced into the cells. Calcium entry is a major signalling event occurring immediately after a temperature downshift. The increase in cytosolic calcium will activate many enzymes, such as phospholipases and calcium dependent-protein kinases. A MAP-kinase module has been shown to be involved in the cold response. Ultimately, the activation of those signalling pathways leads to changes to the transcriptome. In this review we have focused on the genetic and signalling pathways activated early after cold exposure. Much of the data cited is from the model plant Arabidopsis but when possible evidence from other plants is presented.