Ministère de l'Enseignement Supérieur, de la Recherche et de l'Espace

Core Ideas OZCAR is a network of sites studying the critical zone. OZCAR covers various disciplines. OZCAR will help disciplines to work together for a better representation and modeling of the critical zone. The French critical zone initiative, called OZCAR (Observatoires de la Zone Critique–Application et Recherche or Critical Zone Observatories–Application and Research) is a National Research Infrastructure (RI). OZCAR‐RI is a network of instrumented sites, bringing together 21 pre‐existing research observatories monitoring different compartments of the zone situated between “the rock and the sky,” the Earth's skin or critical zone (CZ), over the long term. These observatories are regionally based and have specific initial scientific questions, monitoring strategies, databases, and modeling activities. The diversity of OZCAR‐RI observatories and sites is well representative of the heterogeneity of the CZ and of the scientific communities studying it. Despite this diversity, all OZCAR‐RI sites share a main overarching mandate, which is to monitor, understand, and predict (“earthcast”) the fluxes of water and matter of the Earth's near surface and how they will change in response to the “new climatic regime.” The vision for OZCAR strategic development aims at designing an open infrastructure, building a national CZ community able to share a systemic representation of the CZ, and educating a new generation of scientists more apt to tackle the wicked problem of the Anthropocene. OZCAR articulates around: (i) a set of common scientific questions and cross‐cutting scientific activities using the wealth of OZCAR‐RI observatories, (ii) an ambitious instrumental development program, and (iii) a better interaction between data and models to integrate the different time and spatial scales. Internationally, OZCAR‐RI aims at strengthening the CZ community by providing a model of organization for pre‐existing observatories and by offering CZ instrumented sites. OZCAR is one of two French mirrors of the European Strategy Forum on Research Infrastructure (eLTER‐ESFRI) project.

Abstract Smooth and wrinkled pea cultivars were studied to evaluate the protein content of the seeds, the proportion of albumins to globulins and the variability of the vicilin/legumin ratio. Principal components analysis showed a strong negative correlation between albumin and globulin contents. Stepwise discriminant analysis demonstrated that two variables, protein content and vicilin/legumin ratio, divided the samples into smooth and wrinkled cultivars with a percentage of success of 95%. In addition, the vicilin/legumin ratio tended to increase, the lower the protein content is.

The adult central nervous system (CNS) of the zebrafish, owing to its enrichment in constitutive neurogenic niches, is becoming an increasingly used model to address fundamental questions pertaining to adult neural stem cell (NSC) biology, adult neurogenesis and neuronal repair. Studies conducted in several CNS territories (notably the telencephalon, retina, midbrain, cerebellum and spinal cord) highlighted the presence, in these niches, of progenitor cells displaying NSC-like characters. While pointing to radial glial cells (RG) as major long-lasting, constitutively active and/or activatable progenitors in most domains, these studies also revealed a high heterogeneity in the progenitor subtypes used at the top of neurogenic hierarchies, including the persistence of neuroepithelial (NE) progenitors in some areas. Likewise, dissecting the molecular pathways underlying RG maintenance and recruitment under physiological conditions and upon repair in the zebrafish model revealed shared processes but also specific cascades triggering or sustaining reparative NSC recruitment. Together, the zebrafish adult brain reveals an extensive complexity of adult NSC niches, properties and control pathways, which extends existing understanding of adult NSC biology and gives access to novel mechanisms of efficient NSC maintenance and recruitment in an adult vertebrate brain.

Amyotrophic lateral sclerosis (ALS) is a progressive disorder of unknown origin. Respiratory involvement is the principal cause of death, and dyspnoea is a major source of discomfort. In this study, diaphragm function is described and its relationship with dyspnoea examined in 48 ALS patients (32 male, age 26-80 yrs). The detailed neurological and respiratory evaluation (clinical examination, pulmonary function tests, static pressures, mouth twitch pressures (Pm,t), electromyographic responses to phrenic nerve stimulation and cortical magnetic stimulation were analysed after stratification according to dyspnoea. Dyspnoeic (group I) and nondyspnoeic (group II) patients were similar, bulbar signs being more frequent in group I. Vital capacity was lower in group I (mean+/-SD 67.9+/-22.7 versus 87.9+/-15.6% of the predicted value, p=0.0028), as were maximal static inspiratory pressure (41+/-24 versus 60+/-27% pred, p=0.0242) maximal static inspiratory pressure (18+/-11 versus 32+/-14% pred, p=0.0042), and Pm,t (3.71+/-2.5 versus 7.26+/-3.45 cmH2O, p=0.0011). Abdominal (Abd) paradox and respiratory pulse were frequent in group I (15 of 25 and 14 of 25) but absent or rare in group II (0 of 23 and four of 23) (p<0.05). The electromyographic responses to phrenic and cortical stimulation were generally abnormal in group I but subnormal in group II. Multivariate analysis selected only signs of diaphragm dysfunction (namely, Abd paradox and abnormal electromyographic responses) as significant predictors of dyspnoea. It is concluded that dyspnoea in amyotrophic lateral sclerosis patients should prompt diaphragm function tests.

We have studied the genomic structure and constructed the SpeI, PacI and I-CeuI restriction maps of the four biovars of the pathogenic bacterium Brucella suis. B. suis biovar 1 has two chromosomes of 2.1 Mb and 1.15 Mb, similar to those of the other Brucella species: B. melitensis, B. abortus, B. ovis and B. neotomae. Two chromosomes were also observed in the genome of B. suis biovars 2 and 4, but with sizes of 1.85 Mb and 1.35 Mb, whereas only one chromosome with a size of 3.1 Mb was found in B. suis biovar 3. We show that the differences in chromosome size and number can be explained by rearrangements at chromosomal regions containing the three rrn genes. The location and orientation of these genes confirmed that these rearrangements are due to homologous recombination at the rrn loci. This observation allows us to propose a scheme for the evolution of the genus Brucella in which the two chromosome-containing strains can emerge from an hypothetical ancestor with a single chromosome, which is probably similar to that of B. suis biovar 3. As the genus Brucella is certainly monospecific, this is the first time that differences in chromosome number have been observed in strains of the same bacterial species.

Proteins of the bone morphogenetic protein (BMP) family are known to have a role in ocular and skeletal development; however, because of their widespread expression and functional redundancy, less progress has been made identifying the roles of individual BMPs in human disease. We identified seven heterozygous mutations in growth differentiation factor 6 (GDF6), a member of the BMP family, in patients with both ocular and vertebral anomalies, characterized their effects with a SOX9-reporter assay and western analysis, and demonstrated comparable phenotypes in model organisms with reduced Gdf6 function. We observed a spectrum of ocular and skeletal anomalies in morphant zebrafish, the latter encompassing defective tail formation and altered expression of somite markers noggin1 and noggin2. Gdf6(+/-) mice exhibited variable ocular phenotypes compatible with phenotypes observed in patients and zebrafish. Key differences evident between patients and animal models included pleiotropic effects, variable expressivity and incomplete penetrance. These data establish the important role of this determinant in ocular and vertebral development, demonstrate the complex genetic inheritance of these phenotypes, and further understanding of BMP function and its contributions to human disease.

Congenital cataracts are a major cause of bilateral visual impairment in childhood. We mapped the gene responsible for autosomal congenital cerulean cataracts to chromosome 2q33-35 in a four generation family of Moroccan descent. The maximum lod score (7.19 at recombination fraction theta=0) was obtained for marker D2S2208 near the gamma-crystallin gene (CRYG) cluster. Sequencing of the coding regions of the CRYGA, B, C, and D genes showed the presence of a heterozygous C>A transversion in exon 2 of CRYGD that is associated with cataracts in this family. This mutation resulted in a proline to threonine substitution at amino acid 23 of the protein in the first of the four Greek key motifs that characterise this protein. We show that although the x ray crystallography modelling does not indicate any change of the backbone conformation, the mutation affects a region of the Greek key motif that is important for determining the topology of this protein fold. Our data suggest strongly that the proline to threonine substitution may alter the protein folding or decrease the thermodynamic stability or solubility of the protein. Furthermore, this is the first report of a mutation in this gene resulting in autosomal dominant congenital cerulean cataracts.

The extensor tendons to the fingers were studied in dissections of 50 fresh cadaveric hands, and the divisions of the tendons, as well as the communications (juncturae), were analyzed. The pattern of distribution most frequently observed was as follows. The extensor digitorum communis provided one tendon to the index finger, one to the middle finger, two to the ring finger, and none to the little finger. The extensor indicis exhibited one tendon, whereas the extensor digiti minimi exhibited two tendons. The extensor indicis tendon was always observed to lack a junctura tendinum. The extensor indicis was absent in both hands of one cadaver. A tendon slip from the extensor digiti minimi to the ring finger was observed in one hand. All surgeons must bear in mind the existence of these variations when performing common tendon transfers.

Abstract Massive stars disrupt their natal molecular cloud material through radiative and mechanical feedback processes. These processes have profound effects on the evolution of interstellar matter in our Galaxy and throughout the universe, from the era of vigorous star formation at redshifts of 1–3 to the present day. The dominant feedback processes can be probed by observations of the Photo-Dissociation Regions (PDRs) where the far-ultraviolet photons of massive stars create warm regions of gas and dust in the neutral atomic and molecular gas. PDR emission provides a unique tool to study in detail the physical and chemical processes that are relevant for most of the mass in inter- and circumstellar media including diffuse clouds, proto-planetary disks, and molecular cloud surfaces, globules, planetary nebulae, and star-forming regions. PDR emission dominates the infrared (IR) spectra of star-forming galaxies. Most of the Galactic and extragalactic observations obtained with the James Webb Space Telescope (JWST) will therefore arise in PDR emission. In this paper we present an Early Release Science program using the MIRI, NIRSpec, and NIRCam instruments dedicated to the observations of an emblematic and nearby PDR: the Orion Bar. These early JWST observations will provide template data sets designed to identify key PDR characteristics in JWST observations. These data will serve to benchmark PDR models and extend them into the JWST era. We also present the Science-Enabling products that we will provide to the community. These template data sets and Science-Enabling products will guide the preparation of future proposals on star-forming regions in our Galaxy and beyond and will facilitate data analysis and interpretation of forthcoming JWST observations.

BACKGROUND AND PURPOSE: A cost of illness study was undertaken on behalf of the French Ministry of Health to estimate the annual cost of stroke in France with the goal of better understanding the current economic burden so that improved strategies for care may be developed. METHODS: Using primary data from exhaustive national databases and both top-down and bottom-up approaches, the stroke-related costs for healthcare, nursing care and lost productivity were estimated. RESULTS: The total healthcare cost of stroke patients in France in 2007 was €5.3 billion, 92% of which was borne by statutory health insurance. The average cost of incident cases was €16 686 per patient in the first year, while the annual cost of prevalent cases was a little less than half that amount (€8099). Nursing care costs were estimated at €2.4 billion. Lost productivity reached €255.9 million and that income loss for stroke patients was partially compensated by €63.3 million in social benefit payments. CONCLUSIONS: With healthcare costs representing 3% of total health expenditure in France, stroke constitutes an ongoing burden for the health system and overall economy. Nursing care added nearly half again the amount spent on healthcare, while productivity losses were more limited because nearly 80% of acute incident strokes were in patients over age 65. The high cost of illness underscores the need for improved prevention and interventions to limit the disabling effects of stroke.

PURPOSE: The PAX6 gene was first described as a candidate for human aniridia. However, PAX6 expression is not restricted to the eye and it appears to be crucial for brain development. We studied PAX6 mutations in a large spectrum of patients who presented with aniridia phenotypes, Peters' anomaly, and anterior segment malformations associated or not with neurological anomalies. METHODS: Patients and related families were ophthalmologically phenotyped, and in some cases neurologically and endocrinologically examined. We screened the PAX6 gene by direct sequencing in three groups of patients: those affected by aniridia; those with diverse ocular manifestations; and those with Peters' anomaly. Two mutations were investigated by generating crystallographic representations of the amino acid changes. RESULTS: Three novel heterozygous mutations affecting three unrelated families were identified: the g.572T>C nucleotide change, located in exon 5, and corresponding to the Leucine 46 Proline amino-acid mutation (L46P); the g.655A>G nucleotide change, located in exon 6, and corresponding to the Serine 74 Glycine amino-acid mutation (S74G); and the nucleotide deletion 579delG del, located in exon 6, which induces a frameshift mutation leading to a stop codon (V48fsX53). The L46P mutation was identified in affected patients presenting bilateral microphthalmia, cataracts, and nystagmus. The S74G mutation was found in a large family that had congenital ocular abnormalities, diverse neurological manifestations, and variable cognitive impairments. The 579delG deletion (V48fsX53) caused in the affected members of the same family bilateral aniridia associated with congenital cataract, foveal hypolasia, and nystagmus. We also detected a novel intronic nucleotide change, IVS2+9G>A (very likely a mutation) in an apparently isolated patient affected by a complex ocular phenotype, characterized primarily by a bilateral microphthalmia. Whether this nucleotide change is indeed pathogenic remains to be demonstrated. Two previously known heterozygous mutations of the PAX6 gene sequence were also detected in patients affected by aniridia: a de novo previously known nucleotide change, g.972C>T (Q179X), in exon 8, leading to a stop codon and a heterozygous g.555C>A (C40X) recurrent nonsense mutation in exon 5. No mutations were found in patients with Peters' anomaly. CONCLUSIONS: We identified three mutations associated with aniridia phenotypes (Q179X, C40X, and V48fsX53). The three other mutations reported here cause non-aniridia ocular phenotypes associated in some cases with neurological anomalies. The IVS2+9G>A nucleotide change was detected in a patient with a microphthalmia phenotype. The L46P mutation was detected in a family with microphthalmia, cataract, and nystagmus. This mutation is located in the DNA-binding paired-domain and the crystallographic representations of this mutation show that this mutation may affect the helix-turn-helix motif, and as a consequence the DNA-binding properties of the resulting mutated protein. Ser74 is located in the PAX6 PD linker region, essential for DNA recognition and DNA binding, and the side chain of the Ser74 contributes to DNA recognition by the linker domain through direct contacts. Crystallographic representations show that the S74G mutation results in no side chain and therefore perturbs the DNA-binding properties of PAX6. This study highlights the severity and diversity of the consequences of PAX6 mutations that appeared to result from the complexity of the PAX6 gene structure, and the numerous possibilities for DNA binding. This study emphasizes the fact that neurodevelopmental abnormalities may be caused by PAX6 mutations. The neuro-developmental abnormalities caused by PAX6 mutations are probably still overlooked in the current clinical examinations performed throughout the world in patients affected by PAX6 mutations.

An increase in circulating adrenal catecholamine levels constitutes one of the mechanisms whereby organisms cope with stress. Accordingly, stimulus-secretion coupling within the stressed adrenal medullary tissue undergoes persistent remodeling. In particular, cholinergic synaptic neurotransmission between splanchnic nerve terminals and chromaffin cells is upregulated in stressed rats. Since synaptic transmission is mainly supported by activation of postsynaptic neuronal acetylcholine nicotinic receptors (nAChRs), we focused our study on the role of alpha9-containing nAChRs, which have been recently described in chromaffin cells. Taking advantage of their specific blockade by the alpha-conotoxin RgIA (alpha-RgIA), we unveil novel functional roles for these receptors in the stimulus-secretion coupling of the medulla. First, we show that in rat acute adrenal slices, alpha9-containing nAChRs codistribute with synaptophysin and significantly contribute to EPSCs. Second, we show that these receptors are involved in the tonic inhibitory control exerted by cholinergic activity on gap junctional coupling between chromaffin cells, as evidenced by an increased Lucifer yellow diffusion within the medulla in alpha-RgIA-treated slices. Third, we unexpectedly found that alpha9-containing nAChRs dominantly (>70%) contribute to acetylcholine-induced current in cold-stressed rats, whereas alpha3 nAChRs are the main contributing channels in unstressed animals. Consistently, expression levels of alpha9 nAChR transcript and protein are overexpressed in cold-stressed rats. As a functional relevance, we propose that upregulation of alpha9-containing nAChR channels and ensuing dominant contribution in cholinergic signaling may be one of the mechanisms whereby adrenal medullary tissue appropriately adapts to increased splanchnic nerve electrical discharges occurring in stressful situations.

The Programme for International Student Assessment comparative study of reading performance among 15-year-olds is reanalyzed using statistical procedures that allow the full complexity of the data structures to be explored. The article extends existing multilevel factor analysis and structural equation models and shows how this can extract richer information from the data and provide better fits to the data. It shows how these models can be used fully to explore the dimensionality of the data and to provide efficient, single-stage models that avoid the need for multiple imputation procedures. Markov Chain Monte Carlo methodology for parameter estimation is described.

The effects of concurrent hypoxic/endurance training on mitochondrial respiration in permeabilized fibers in trained athletes were investigated. Eighteen endurance athletes were divided into two training groups: normoxic (Nor, n = 8) and hypoxic (H, n = 10). Three weeks (W1-W3) of endurance training (5 sessions of 1 h to 1 h and 30 min per week) were completed. All training sessions were performed under normoxic [160 Torr inspired Po(2) (Pi(O(2)))] or hypoxic conditions ( approximately 100 Torr Pi(O(2)), approximately 3,000 m) for Nor and H group, respectively, at the same relative intensity. Before and after the training period, an incremental test to exhaustion in normoxia was performed, muscle biopsy samples were taken from the vastus lateralis, and mitochondrial respiration in permeabilized fibers was measured. Peak power output (PPO) increased by 7.2% and 6.6% (P < 0.05) for Nor and H, respectively, whereas maximal O(2) uptake (Vo(2 max)) remained unchanged: 58.1 +/- 0.8 vs. 61.0 +/- 1.2 ml.kg(-1).min(-1) and 58.5 +/- 0.7 vs. 58.3 +/- 0.6 ml.kg(-1).min(-1) for Nor and H, respectively, between pretraining (W0) and posttraining (W4). Maximal ADP-stimulated mitochondrial respiration significantly increased for glutamate + malate (6.27 +/- 0.37 vs. 8.51 +/- 0.33 mumol O(2).min(-1).g dry weight(-1)) and significantly decreased for palmitate + malate (3.88 +/- 0.23 vs. 2.77 +/- 0.08 mumol O(2).min(-1).g dry weight(-1)) in the H group. In contrast, no significant differences were found for the Nor group. The findings demonstrate that 1) a 3-wk training period increased the PPO at sea level without any changes in Vo(2 max), and 2) a 3-wk hypoxic exercise training seems to alter the intrinsic properties of mitochondrial function, i.e., substrate preference.

The proximal promoter region of the human transferrin gene contains an hepatocyte-specific cis-element (PRI, nucleotides -76 to -51) whose DNA sequence is homologous to a sequence (nucleotides -89 to -68) present in the transcriptionally essential 5' region of the human antithrombin III gene and to another hepatocyte-specific sequence (A domain) of the human alpha 1-antitrypsin gene promoter. The results reported here lead to the conclusion that the liver trans-acting factor Tf-LF1, binding to the transferrin PRI cis-element interacts with the homologous antithrombin III region, but is different from the transcription factor LF-A1 interacting with the A domain of the alpha 1-antitrypsin promoter. The distal region DRI (nucleotides -480 to -454) of the human transferrin gene promoter presents in its core the same 10 nucleotide-long sequence as the PRI cis-element. We have previously shown that the liver protein Tf-LF2, binding to the DRI element is different from the Tf-LF1 trans-acting factor. In this paper we also show that Tf-LF2 is different from the transcription factor LF-A1 interacting with the alpha 1-antitrypsin promoter. The results allow us to conclude that at least three distinct liver nuclear proteins bind to different subsets of 5' DNA regions containing similar sequences. These sequences are present in genes expressed essentially in liver.

The sparse-matrix-flat-surface iterative approach has been implemented for perfectly conducting surfaces and modified to enhance convergence stability and speed for very rough surfaces. Monte Carlo simulations of backscattering enhancement using a beam decomposition technique are compared with millimeter-wave laboratory experimental data. Strong but finite conductivity for metals or thin skin depth for dielectrics is simulated by an impedance approximation. This gives rise to a nonhypersingular integral equation derived from the magnetic field integral equation. The effect of finite conductivity for a metal at visible wavelengths is shown.

BACKGROUND: Little is known on the impact of immunosuppressive drugs on the development of the different T-cell subsets that compose the immune balance. We have explored the influence of mycophenolic acid (MPA) and tacrolimus on T cells response with a special focus on the Th17-cell subset. METHODS: In an in vitro model of human CD4 cells activation, we first compared the influence of MPA and tacrolimus on the transcription of different set of genes related to each of the main T-cell subsets and then investigated how these two drugs interfere with interleukin (IL)-17 production. We also studied, in stable kidney transplant patients, the relation between IL-17 serum concentration and systemic drug exposure. RESULTS: MPA and tacrolimus exhibited a comparable impact on T-cell response, dampening most Th1-related genes transcription and preserving regulatory T cells/Th2 molecular phenotypes. Although both MPA and tacrolimus decreased Th17-related transcripts after T-cell activation, MPA exerted a stronger inhibitory effect on IL-17 production than tacrolimus. Accordingly, renal transplant patients treated with MPA in combination with minimized dose of tacrolimus tended to have lower circulating IL-17 levels than patients treated with tacrolimus alone given at conventional dose. CONCLUSIONS: A treatment combining MPA and tacrolimus is susceptible to favorably tip the immune balance and might confer optimal allograft immunoprotection. Because of its ability to profoundly inhibit IL-17 production, MPA may help to better overcome Th17-related alloreactivity in the context of calcineurin inhibitor-minimizing protocol.

Abstract Einstein Telescope (ET) is the European project for a gravitational-wave (GW) observatory of third-generation. In this paper we present a comprehensive discussion of its science objectives, providing state-of-the-art predictions for the capabilities of ET in both geometries currently under consideration, a single-site triangular configuration or two L-shaped detectors. We discuss the impact that ET will have on domains as broad and diverse as fundamental physics, cosmology, early Universe, astrophysics of compact objects, physics of matter in extreme conditions, and dynamics of stellar collapse. We discuss how the study of extreme astrophysical events will be enhanced by multi-messenger observations. We highlight the ET synergies with ground-based and space-borne GW observatories, including multi-band investigations of the same sources, improved parameter estimation, and complementary information on astrophysical or cosmological mechanisms obtained combining observations from different frequency bands. We present advancements in waveform modeling dedicated to third-generation observatories, along with open tools developed within the ET Collaboration for assessing the scientific potentials of different detector configurations. We finally discuss the data analysis challenges posed by third-generation observatories, which will enable access to large populations of sources and provide unprecedented precision.

A heterogenous population of envelope glycoprotein-specific cytotoxic effector cells are found in the peripheral blood of individuals infected with HIV-1, and in many cases env-specific lysis is not restricted by MHC molecules and is not blocked by antibody to CD3 (Rivière, Y. et al., J. Virol. 1989, 63:2270). In order to detect env-specific cytotoxic T lymphocytes (CTL) in fresh peripheral blood mononuclear cells of HIV-1-infected donors, a mutant env gene with deletion of the amino-terminal signal sequence was inserted into vaccinia virus. This deletion of the amino-terminal signal sequence was inserted into vaccinia virus. This deletion results in synthesis of an envelope protein that is not glycosylated and not expressed at the surface of infected cells. Target cells infected with this recombinant vaccinia virus are not lysed by antibody-mediated cellular cytotoxicity, but they are recognized by secondary CTL. Comparing lysis of target cells expressing gp160 of HIV-1 and the signal peptide deletion mutant, primary env-specific CTL were detected in some individuals infected with HIV-1.

The TF on Scholarly Infrastructures of Research Software, as part of the Architecture WG of the European Open Science Cloud (EOSC) Executive Board, has established a set of recommendations to allow EOSC to include software, next to other research outputs like publications and data, in the realm of its research artifacts. This work is built upon a survey and documentation of a representative panel of current operational infrastructures acrossEurope, comparing their scopes and approaches.This report summarizes the state of the art, identifies best practices, as well as open problems, and paves the way for federating the different approaches in view of supporting the software pillar of EOSC.