Showing papers by "Paul Sabatier University published in 2011"

True Performance Metrics in Electrochemical Energy Storage

Abstract: A dramatic expansion of research in the area of electrochemical energy storage (EES) during the past decade has been driven by the demand for EES in handheld electronic devices, transportation, and storage of renewable energy for the power grid (1-3). However, the outstanding properties reported for new electrode materials may not necessarily be applicable to performance of electrochemical capacitors (ECs). These devices, also called supercapacitors or ultra-capacitors (4), store charge with ions from solution at charged porous electrodes. Unlike batteries, which store large amounts of energy but deliver it slowly, ECs can deliver energy faster (develop high power), but only for a short time. However, recent work has claimed energy densities for ECs approaching (5) or even exceeding that of batteries. We show that even when some metrics seem to support these claims, actual device performance may be rather mediocre. We will focus here on ECs, but these considerations also apply to lithium (Li)--ion batteries.

How simple rules determine pedestrian behavior and crowd disasters

Abstract: With the increasing size and frequency of mass events, the study of crowd disasters and the simulation of pedestrian flows have become important research areas. However, even successful modeling approaches such as those inspired by Newtonian force models are still not fully consistent with empirical observations and are sometimes hard to calibrate. Here, a cognitive science approach is proposed, which is based on behavioral heuristics. We suggest that, guided by visual information, namely the distance of obstructions in candidate lines of sight, pedestrians apply two simple cognitive procedures to adapt their walking speeds and directions. Although simpler than previous approaches, this model predicts individual trajectories and collective patterns of motion in good quantitative agreement with a large variety of empirical and experimental data. This model predicts the emergence of self-organization phenomena, such as the spontaneous formation of unidirectional lanes or stop-and-go waves. Moreover, the combination of pedestrian heuristics with body collisions generates crowd turbulence at extreme densities—a phenomenon that has been observed during recent crowd disasters. By proposing an integrated treatment of simultaneous interactions between multiple individuals, our approach overcomes limitations of current physics-inspired pair interaction models. Understanding crowd dynamics through cognitive heuristics is therefore not only crucial for a better preparation of safe mass events. It also clears the way for a more realistic modeling of collective social behaviors, in particular of human crowds and biological swarms. Furthermore, our behavioral heuristics may serve to improve the navigation of autonomous robots.

Fungal lipochitooligosaccharide symbiotic signals in arbuscular mycorrhiza

Abstract: Arbuscular mycorrhiza (AM) is a root endosymbiosis between plants and glomeromycete fungi. It is the most widespread terrestrial plant symbiosis, improving plant uptake of water and mineral nutrients. Yet, despite its crucial role in land ecosystems, molecular mechanisms leading to its formation are just beginning to be unravelled. Recent evidence suggests that AM fungi produce diffusible symbiotic signals. Here we show that Glomus intraradices secretes symbiotic signals that are a mixture of sulphated and non-sulphated simple lipochitooligosaccharides (LCOs), which stimulate formation of AM in plant species of diverse families (Fabaceae, Asteraceae and Umbelliferae). In the legume Medicago truncatula these signals stimulate root growth and branching by the symbiotic DMI signalling pathway. These findings provide a better understanding of the evolution of signalling mechanisms involved in plant root endosymbioses and will greatly facilitate their molecular dissection. They also open the way to using these natural and very active molecules in agriculture.

Fluoxetine for motor recovery after acute ischaemic stroke (FLAME): a randomised placebo-controlled trial

Abstract: Summary Background Hemiplegia and hemiparesis are the most common deficits caused by stroke. A few small clinical trials suggest that fluoxetine enhances motor recovery but its clinical efficacy is unknown. We therefore aimed to investigate whether fluoxetine would enhance motor recovery if given soon after an ischaemic stroke to patients who have motor deficits. Methods In this double-blind, placebo-controlled trial, patients from nine stroke centres in France who had ischaemic stroke and hemiplegia or hemiparesis, had Fugl-Meyer motor scale (FMMS) scores of 55 or less, and were aged between 18 years and 85 years were eligible for inclusion. Patients were randomly assigned, using a computer random-number generator, in a 1:1 ratio to fluoxetine (20 mg once per day, orally) or placebo for 3 months starting 5–10 days after the onset of stroke. All patients had physiotherapy. The primary outcome measure was the change on the FMMS between day 0 and day 90 after the start of the study drug. Participants, carers, and physicians assessing the outcome were masked to group assignment. Analysis was of all patients for whom data were available (full analysis set). This trial is registered with ClinicalTrials.gov, number NCT00657163. Findings 118 patients were randomly assigned to fluoxetine (n=59) or placebo (n=59), and 113 were included in the analysis (57 in the fluoxetine group and 56 in the placebo group). Two patients died before day 90 and three withdrew from the study. FMMS improvement at day 90 was significantly greater in the fluoxetine group (adjusted mean 34·0 points [95% CI 29·7–38·4]) than in the placebo group (24·3 points [19·9–28·7]; p=0·003). The main adverse events in the fluoxetine and placebo groups were hyponatraemia (two [4%] vs two [4%]), transient digestive disorders including nausea, diarrhoea, and abdominal pain (14 [25%] vs six [11%]), hepatic enzyme disorders (five [9%] vs ten [18%]), psychiatric disorders (three [5%] vs four [7%]), insomnia (19 [33%] vs 20 [36%]), and partial seizure (one [ vs 0). Interpretation In patients with ischaemic stroke and moderate to severe motor deficit, the early prescription of fluoxetine with physiotherapy enhanced motor recovery after 3 months. Modulation of spontaneous brain plasticity by drugs is a promising pathway for treatment of patients with ischaemic stroke and moderate to severe motor deficit. Funding Public French National Programme for Clinical Research.

Lead Uptake, Toxicity, and Detoxification in Plants

Abstract: Plants are the target of a wide range of pollutants that vary in concentration, speciation, and toxicity. Such pollutants mainly enter the plant system through the soil (Arshad et al. 2008) or via the atmosphere (Uzu et al. 2010). Among common pollutants that affect plants, lead is among the most toxic and frequently encountered (Cecchi et al. 2008; Grover et al. 2010; Shahid et al. 2011). Lead continues to be used widely in many industrial processes and occurs as a contaminant in all environmental compartments (soils, water, the atmosphere, and living organisms). The prominence of environmental lead contamination results both from its persistence (Islam et al. 2008; Andra et al. 2009; Punamiya et al. 2010) and from its present and past numerous sources. These sources have included smelting, combustion of leaded gasoline, or applications of lead-contaminated media (sewage sludge and fertilizers) to land (Piotrowska et al. 2009; Gupta et al. 2009; Sammut et al. 2010; Grover et al. 2010). In 2009, production of recoverable lead from mining operations was 1690, 516, and 400 thousand metric tons by China, Australia, and the USA, respectively (USGS 2009).

Beyond DNA: integrating inclusive inheritance into an extended theory of evolution

Abstract: Many biologists are calling for an 'extended evolutionary synthesis' that would 'modernize the modern synthesis' of evolution. Biological information is typically considered as being transmitted across generations by the DNA sequence alone, but accumulating evidence indicates that both genetic and non-genetic inheritance, and the interactions between them, have important effects on evolutionary outcomes. We review the evidence for such effects of epigenetic, ecological and cultural inheritance and parental effects, and outline methods that quantify the relative contributions of genetic and non-genetic heritability to the transmission of phenotypic variation across generations. These issues have implications for diverse areas, from the question of missing heritability in human complex-trait genetics to the basis of major evolutionary transitions.

Constraining Dark Matter Models from a Combined Analysis of Milky Way Satellites with the Fermi Large Area Telescope

Abstract: Satellite galaxies of the Milky Way are among the most promising targets for dark matter searches in gamma rays. We present a search for dark matter consisting of weakly interacting massive particl ...

Height-diameter allometry of tropical forest trees

Abstract: . Tropical tree height-diameter (H:D) relationships may vary by forest type and region making large-scale estimates of above-ground biomass subject to bias if they ignore these differences in stem allometry. We have therefore developed a new global tropical forest database consisting of 39 955 concurrent H and D measurements encompassing 283 sites in 22 tropical countries. Utilising this database, our objectives were: 1. to determine if H:D relationships differ by geographic region and forest type (wet to dry forests, including zones of tension where forest and savanna overlap). 2. to ascertain if the H:D relationship is modulated by climate and/or forest structural characteristics (e.g. stand-level basal area, A). 3. to develop H:D allometric equations and evaluate biases to reduce error in future local-to-global estimates of tropical forest biomass. Annual precipitation coefficient of variation (PV), dry season length (SD), and mean annual air temperature (TA) emerged as key drivers of variation in H:D relationships at the pantropical and region scales. Vegetation structure also played a role with trees in forests of a high A being, on average, taller at any given D. After the effects of environment and forest structure are taken into account, two main regional groups can be identified. Forests in Asia, Africa and the Guyana Shield all have, on average, similar H:D relationships, but with trees in the forests of much of the Amazon Basin and tropical Australia typically being shorter at any given D than their counterparts elsewhere. The region-environment-structure model with the lowest Akaike's information criterion and lowest deviation estimated stand-level H across all plots to within amedian −2.7 to 0.9% of the true value. Some of the plot-to-plot variability in H:D relationships not accounted for by this model could be attributed to variations in soil physical conditions. Other things being equal, trees tend to be more slender in the absence of soil physical constraints, especially at smaller D. Pantropical and continental-level models provided less robust estimates of H, especially when the roles of climate and stand structure in modulating H:D allometry were not simultaneously taken into account.

Ultrasonography of optic nerve sheath diameter for detection of raised intracranial pressure: a systematic review and meta-analysis

Abstract: To evaluate the diagnostic accuracy of ultrasonography of optic nerve sheath diameter (ONSD) for assessment of intracranial hypertension. Systematic review without language restriction based on electronic databases, with manual review of literature and conference proceedings until July 2010. Studies were eligible if they compared ultrasonography of ONSD with intracranial pressure (ICP) monitoring. Data were extracted independently by three authors. Random-effects meta-analysis and meta-regression were performed. Six studies including 231 patients were reviewed. No significant heterogeneity was detected for sensitivity, specificity, positive and negative likelihood ratios or diagnostic odds ratio. For detection of raised intracranial pressure, pooled sensitivity was 0.90 [95% confidence interval (CI) 0.80–0.95; p for heterogeneity, p het = 0.09], pooled specificity was 0.85 (95% CI 0.73–0.93, p het = 0.13), and the pooled diagnostic odds ratio was 51 (95% CI 22–121). The area under the summary receiver-operating characteristic (SROC) curve was 0.94 (95% CI 0.91–0.96). Ultrasonography of ONSD shows a good level of diagnostic accuracy for detecting intracranial hypertension. In clinical decision-making, this technique may help physicians decide to transfer patients to specialized centers or to place an invasive device when specific recommendations for this placement do not exist.

The global dust SED: tracing the nature and evolution of dust with DustEM

Abstract: The Planck and Herschel missions are currently measuring the far-infrared to millimeter emission of dust, which combined with existing IR data, will for the first time provide the full spectral energy distribution (SED) of the galactic interstellar medium dust emission, from the mid-IR to the mm range, with an unprecedented sensitivity and down to spatial scales ∼30 �� . Such a global SED will allow a systematic study of the dust evolution processes (e.g. grain growth or fragmentation) that directly affect the SED because they redistribute the dust mass among the observed grain sizes. The dust SED is also affected by variations of the radiation field intensity. Here we present a versatile numerical tool, DustEM, that predicts the emission and extinction of dust grains given their size distribution and their optical and thermal properties. In order to model dust evolution, DustEM has been designed to deal with a variety of grain types, structures and size distributions and to be able to easily include new dust physics. We use DustEM to model the dust SED and extinction in the diffuse interstellar medium at high-galactic latitude (DHGL), a natural reference SED that will allow us to study dust evolution. We present a coherent set of observations for the DHGL SED, which has been obtained by correlating the IR and HI-21 cm data. The dust components in our DHGL model are (i) polycyclic aromatic hydrocarbons; (ii) amorphous carbon and (iii) amorphous silicates. We use amorphous carbon dust, rather than graphite, because it better explains the observed high abundances of gas-phase carbon in shocked regions of the interstellar medium. Using the DustEM model, we illustrate how, in the optically thin limit, the IRAS/Planck HFI (and likewise Spitzer/Herschel for smaller spatial scales) photometric band ratios of the dust SED can disentangle the influence of the exciting radiation field intensity and constrain the abundance of small grains (a < 10 nm) relative to the larger grains. We also discuss the contributions of the different grain populations to the IRAS, Planck (and similarly to Herschel) channels. Such information is required to enable a study of the evolution of dust as well as to systematically extract the dust thermal emission from CMB data and to analyze the emission in the Planck polarized channels. The DustEM code described in this paper is publically available. Dust plays a key role in the physics (e.g. heating of the gas, coupling to the magnetic field) and chemistry (formation of H2, shielding of molecules from dissociative radiation) of the interstellar medium (ISM). Heated by stellar photons, dust grains radiate away the absorbed energy by emission in the near-IR to mm range. Dust emission can thus be used as a tracer of the radiation field intensity and, hence, of star formation activity. Assuming a constant dust abundance, the far-IR to mm dust emission is also used to derive the total column density along a line of sight and to provide mass estimates. The impact of dust on the ISM and the use of its emission as a tracer of the local conditions depends on the dust properties and abundances. It is therefore of major importance to understand dust properties and their evolution throughout the ISM. The instruments onboard the Herschel and Planck satel

Functional Structure of Biological Communities Predicts Ecosystem Multifunctionality

Abstract: The accelerating rate of change in biodiversity patterns, mediated by ever increasing human pressures and global warming, demands a better understanding of the relationship between the structure of biological communities and ecosystem functioning (BEF). Recent investigations suggest that the functional structure of communities, i.e. the composition and diversity of functional traits, is the main driver of ecological processes. However, the predictive power of BEF research is still low, the integration of all components of functional community structure as predictors is still lacking, and the multifunctionality of ecosystems (i.e. rates of multiple processes) must be considered. Here, using a multiple-processes framework from grassland biodiversity experiments, we show that functional identity of species and functional divergence among species, rather than species diversity per se, together promote the level of ecosystem multifunctionality with a predictive power of 80%. Our results suggest that primary productivity and decomposition rates, two key ecosystem processes upon which the global carbon cycle depends, are primarily sustained by specialist species, i.e. those that hold specialized combinations of traits and perform particular functions. Contrary to studies focusing on single ecosystem functions and considering species richness as the sole measure of biodiversity, we found a linear and non-saturating effect of the functional structure of communities on ecosystem multifunctionality. Thus, sustaining multiple ecological processes would require focusing on trait dominance and on the degree of community specialization, even in species-rich assemblages.

Multicomponent reactions and ionic liquids: a perfect synergy for eco-compatible heterocyclic synthesis

Abstract: The efficiency of a chemical synthesis can be nowadays measured, not only by parameters like selectivity and overall yield, but also by its raw material, time, human resources and energy requirements, as well as the toxicity and hazard of the chemicals and the protocols involved. The development of multicomponent reactions (MCRs) in the presence of task-specific ionic liquids (ILs), used not only as environmentally benign reaction media, but also as catalysts, is a new approach that meet with the requirements of sustainable chemistry. The aim of this tutorial review is to highlight the synergistic effect of the combined use of MCRs and ILs for the development of new eco-compatible methodologies for heterocyclic chemistry.

Single-Trial Normalization for Event-Related Spectral Decomposition Reduces Sensitivity to Noisy Trials

Abstract: In electroencephalography, the classical event-related potential model often proves to be a limited method to study complex brain dynamics. For this reason, spectral techniques adapted from signal processing such as event-related spectral perturbation (ERSP) – and its variant event-related synchronization and event-related desynchronization – have been used over the past 20 years. They represent average spectral changes in response to a stimulus. These spectral methods do not have strong consensus for comparing preand post-stimulus activity. When computing ERSP, pre-stimulus baseline removal is usually performed after averaging the spectral estimate of multiple trials. Correcting the baseline of each single-trial prior to averaging spectral estimates is an alternative baseline correction method. However, we show that this method leads to positively skewed post-stimulus ERSP values. We eventually present new single-trial-based ERSP baseline correction methods that perform trial normalization or centering prior to applying classical baseline correction methods. We show that single-trial correction methods minimize the contribution of artifactual data trials with high-amplitude spectral estimates and are robust to outliers when performing statistical inference testing. We then characterize these methods in terms of their time–frequency responses and behavior compared to classical ERSP methods.

Shifted Symplectic Structures

Abstract: This is the first of a series of papers about \emph{quantization} in the context of \emph{derived algebraic geometry}. In this first part, we introduce the notion of \emph{$n$-shifted symplectic structures}, a generalization of the notion of symplectic structures on smooth varieties and schemes, meaningful in the setting of derived Artin n-stacks. We prove that classifying stacks of reductive groups, as well as the derived stack of perfect complexes, carry canonical 2-shifted symplectic structures. Our main existence theorem states that for any derived Artin stack $F$ equipped with an $n$-shifted symplectic structure, the derived mapping stack $\textbf{Map}(X,F)$ is equipped with a canonical $(n-d)$-shifted 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 $n$-shifted 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 also show that Lagrangian intersections carry canonical (-1)-shifted symplectic structures.

Partitioning global patterns of freshwater fish beta diversity reveals contrasting signatures of past climate changes

Abstract: Ecology Letters (2011) 14: 325-334 ABSTRACT: Here, we employ an additive partitioning framework to disentangle the contribution of spatial turnover and nestedness to beta diversity patterns in the global freshwater fish fauna. We find that spatial turnover and nestedness differ geographically in their contribution to freshwater fish beta diversity, a pattern that results from contrasting influences of Quaternary climate changes. Differences in fish faunas characterized by nestedness are greater in drainage basins that experienced larger amplitudes of Quaternary climate oscillations. Conversely, higher levels of spatial turnover are found in historically unglaciated drainage basins with high topographic relief, these having experienced greater Quaternary climate stability. Such an historical climate signature is not clearly detected when considering the overall level of beta diversity. Quantifying the relative roles of historical and ecological factors in explaining present-day patterns of beta diversity hence requires considering the different processes generating these patterns and not solely the overall level of beta diversity.

Apelin, diabetes, and obesity.

Abstract: Apelin is a peptide known as the ligand of the G-protein-coupled receptor APJ. Several active apelin forms exist such as apelin-36, apelin-17, apelin-13, and the pyroglutamated form of apelin-13. Apelin and APJ are expressed in the central nervous system, particularly in the hypothalamus and in many peripheral tissues. Apelin has been shown to be involved in the regulation of cardiovascular and fluid homeostasis, food intake, cell proliferation, and angiogenesis. In addition to be an ubiquitous peptide, apelin is also produced and secreted by adipocytes and thus considered as an adipokine. This has opened a new field of investigation establishing a link between apelin and metabolic disorders (obesity, type 2 diabetes, etc.) which is the focus of the present review. Several studies, but not all, have reported an increase of plasma apelin concentrations in humans and in animal models with different metabolic pathologies. Moreover, important roles for apelin both in glucose and lipid metabolism have been highlighted as well as the associated signaling pathways. Apelin appears as a beneficial adipokine with anti-obesity and anti-diabetic properties and thus as a promising therapeutic target in metabolic disorders.

Ongoing EEG Phase as a Trial-by-Trial Predictor of Perceptual and Attentional Variability.

Abstract: Even in well-controlled laboratory environments, apparently identical repetitions of an experimental trial can give rise to highly variable perceptual outcomes and behavioral responses. This variability is generally discarded as a reflection of intrinsic noise in neuronal systems. However, part of this variability may be accounted for by trial-by-trial fluctuations of the phase of ongoing oscillations at the moment of stimulus presentation. For example, the phase of an EEG oscillation reflecting the rapid waxing and waning of sustained attention can predict the perception of a subsequent visual stimulus at threshold. Similar ongoing periodicities account for a portion of the trial-by-trial variability of visual reaction times. We review the available experimental evidence linking ongoing EEG phase to perceptual and attentional variability, and the corresponding methodology. We propose future tests of this relation, and discuss the theoretical implications for understanding the neuronal dynamics of sensory perception.

Fast atomic transport without vibrational heating

Abstract: We use the dynamical invariants associated with the Hamiltonian of an atom in a one dimensional moving trap to inverse engineer the trap motion and perform fast atomic transport without final vibrational heating. The atom is driven nonadiabatically through a shortcut to the result of adiabatic, slow trap motion. For harmonic potentials this only requires designing appropriate trap trajectories, whereas perfect transport in anharmonic traps may be achieved by applying an extra field to compensate the forces in the rest frame of the trap. The results can be extended to atom stopping or launching. The limitations due to geometrical constraints, energies, and accelerations involved are analyzed along with the relation to previous approaches based on classical trajectories or ``fast-forward'' and ``bang-bang'' methods, which can be integrated in the invariant-based framework.

The Lectin Receptor Kinase LecRK-I.9 Is a Novel Phytophthora Resistance Component and a Potential Host Target for a RXLR Effector

Abstract: In plants, an active defense against biotrophic pathogens is dependent on a functional continuum between the cell wall (CW) and the plasma membrane (PM). It is thus anticipated that proteins maintaining this continuum also function in defense. The legume-like lectin receptor kinase LecRK-I.9 is a putative mediator of CW-PM adhesions in Arabidopsis and is known to bind in vitro to the Phytophthora infestans RXLR-dEER effector IPI-O via a RGD cell attachment motif present in IPI-O. Here we show that LecRK-I.9 is associated with the plasma membrane, and that two T-DNA insertions lines deficient in LecRK-I.9 (lecrk-I.9) have a ‘gain-of-susceptibility’ phenotype specifically towards the oomycete Phytophthora brassicae. Accordingly, overexpression of LecRK-I.9 leads to enhanced resistance to P. brassicae. A similar ‘gain-of-susceptibility’ phenotype was observed in transgenic Arabidopsis lines expressing ipiO (35S-ipiO1). This phenocopy behavior was also observed with respect to other defense-related functions; lecrk-I.9 and 35S-ipiO1 were both disturbed in pathogen- and MAMP-triggered callose deposition. By site-directed mutagenesis, we demonstrated that the RGD cell attachment motif in IPI-O is not only essential for disrupting the CW-PM adhesions, but also for disease suppression. These results suggest that destabilizing the CW-PM continuum is one of the tactics used by Phytophthora to promote infection. As countermeasure the host may want to strengthen CW-PM adhesions and the novel Phytophthora resistance component LecRK-I.9 seems to function in this process.

The Impact of Galaxy Interactions on Active Galactic Nucleus Activity in zCosmos

Abstract: Close encounters between galaxies are expected to be a viable mechanism, as predicted by numerical simulations, by which accretion onto supermassive black holes can be initiated. To test this scenario, we construct a sample of 562 galaxies (M_* > 2.5 × 10^(10) M_☉) in kinematic pairs over the redshift range 0.25 2 × 10^(42) erg s^(–1)) detected by Chandra. We find a higher fraction of an AGN in galaxies in pairs relative to isolated galaxies of similar stellar mass. Our result is primarily due to an enhancement of AGN activity, by a factor of 1.9 (observed) and 2.6 (intrinsic), for galaxies in pairs of projected separation less than 75 kpc and line-of-sight velocity offset less than 500 km s^(–1). This study demonstrates that close kinematic pairs are conducive environments for black hole growth, either indicating a causal physical connection or an inherent relation, such as, to enhanced star formation. In the Appendix, we describe a method for estimating the intrinsic fractions of galaxies (either in pairs or the field) hosting an AGN with confidence intervals, and an excess fraction in pairs. We estimate that 17.8^(+8.4)_(–7.4)% of all moderate-luminosity AGN activity takes place within galaxies undergoing early stages of interaction that leaves open the question as to what physical processes are responsible for fueling the remaining ~80% that may include late-stage mergers.

Azospirillum genomes reveal transition of bacteria from aquatic to terrestrial environments.

Abstract: Fossil records indicate that life appeared in marine environments ∼3.5 billion years ago (Gyr) and transitioned to terrestrial ecosystems nearly 2.5 Gyr. Sequence analysis suggests that "hydrobacteria" and "terrabacteria" might have diverged as early as 3 Gyr. Bacteria of the genus Azospirillum are associated with roots of terrestrial plants; however, virtually all their close relatives are aquatic. We obtained genome sequences of two Azospirillum species and analyzed their gene origins. While most Azospirillum house-keeping genes have orthologs in its close aquatic relatives, this lineage has obtained nearly half of its genome from terrestrial organisms. The majority of genes encoding functions critical for association with plants are among horizontally transferred genes. Our results show that transition of some aquatic bacteria to terrestrial habitats occurred much later than the suggested initial divergence of hydro- and terrabacterial clades. The birth of the genus Azospirillum approximately coincided with the emergence of vascular plants on land.

Genome-wide scan identifies TNIP1, PSORS1C1, and RHOB as novel risk loci for systemic sclerosis.

Abstract: Systemic sclerosis (SSc) is an orphan, complex, inflammatory disease affecting the immune system and connective tissue. SSc stands out as a severely incapacitating and life-threatening inflammatory rheumatic disease, with a largely unknown pathogenesis. We have designed a two-stage genome-wide association study of SSc using case-control samples from France, Italy, Germany, and Northern Europe. The initial genome-wide scan was conducted in a French post quality-control sample of 564 cases and 1,776 controls, using almost 500 K SNPs. Two SNPs from the MHC region, together with the 6 loci outside MHC having at least one SNP with a P<10(-5) were selected for follow-up analysis. These markers were genotyped in a post-QC replication sample of 1,682 SSc cases and 3,926 controls. The three top SNPs are in strong linkage disequilibrium and located on 6p21, in the HLA-DQB1 gene: rs9275224, P = 9.18×10(-8), OR = 0.69, 95% CI [0.60-0.79]; rs6457617, P = 1.14×10(-7) and rs9275245, P = 1.39×10(-7). Within the MHC region, the next most associated SNP (rs3130573, P = 1.86×10(-5), OR = 1.36 [1.18-1.56]) is located in the PSORS1C1 gene. Outside the MHC region, our GWAS analysis revealed 7 top SNPs (P<10(-5)) that spanned 6 independent genomic regions. Follow-up of the 17 top SNPs in an independent sample of 1,682 SSc and 3,926 controls showed associations at PSORS1C1 (overall P = 5.70×10(-10), OR:1.25), TNIP1 (P = 4.68×10(-9), OR:1.31), and RHOB loci (P = 3.17×10(-6), OR:1.21). Because of its biological relevance, and previous reports of genetic association at this locus with connective tissue disorders, we investigated TNIP1 expression. A markedly reduced expression of the TNIP1 gene and also its protein product were observed both in lesional skin tissue and in cultured dermal fibroblasts from SSc patients. Furthermore, TNIP1 showed in vitro inhibitory effects on inflammatory cytokine-induced collagen production. The genetic signal of association with TNIP1 variants, together with tissular and cellular investigations, suggests that this pathway has a critical role in regulating autoimmunity and SSc pathogenesis.