Regulatory Network Analyses Reveal Genome-Wide Potentiation of LIF Signaling by Glucocorticoids and Define an Innate Cell Defense Response

While the hypothalamo-pituitary-adrenal axis (HPA) activates a general stress response by increasing glucocorticoid (Gc) synthesis, biological stress resulting from infections triggers the inflammatory response through production of cytokines. The pituitary gland integrates some of these signals by responding to the pro-inflammatory cytokines IL6 and LIF and to a negative Gc feedback loop. The present work used whole-genome approaches to define the LIF/STAT3 regulatory network and to delineate cross-talk between this pathway and Gc action. Genome-wide ChIP-chip identified 3,449 STAT3 binding sites, whereas 2,396 genes regulated by LIF and/or Gc were found by expression profiling. Surprisingly, LIF on its own changed expression of only 85 genes but the joint action of LIF and Gc potentiated the expression of more than a thousand genes. Accordingly, activation of both LIF and Gc pathways also potentiated STAT3 and GR recruitment to many STAT3 targets. Our analyses revealed an unexpected gene cluster that requires both stimuli for delayed activation; 83% of the genes in this cluster are involved in different cell defense mechanisms. Thus, stressors that trigger both general stress and inflammatory responses lead to activation of a stereotypic innate cellular defense response

Design of adaptive 2x2 space-time block codes for broadcasting applications

International audienceFuture broadcasting systems will call for multi-antenna (MIMO) transmission techniques. Space-time block codes (STBC) are conventionally designed according to rank-determinant criteria, efficient at high signal-to-noise ratios (SNR). However, broadcasting transmissions are protected by powerful forward error correcting (FEC) codes able to operate at low to moderate SNRs. The aim of this study is to design full-rate full-diversity STBCs with low detection complexity, optimized for a wide range of SNRs

Multimethod Characterization of the French-Pyrenean Valley of Bagnères-de-Bigorre for Seismic-Hazard Evaluation: Observations and Models

International audienceA narrow rectilinear valley in the French Pyrenees, affected in the past by damaging earthquakes, has been chosen as a test site for soil response characteriza- tion. The main purpose of this initiative was to compare experimental and numerical approaches. A temporary network of 10 stations has been deployed along and across the valley during two years; parallel various experiments have been conducted, in particular ambient noise recording, and seismic profiles with active sources for struc- ture determination at the 10 sites. Classical observables have been measured for site amplification evaluation, such as spectral ratios of horizontal or vertical motions between site and reference stations using direct S waves and S coda, and spectral ratios between horizontal and vertical (H/V) motions at single stations using noise and S-coda records. Vertical shear-velocity profiles at the stations have first been obtained from a joint inversion of Rayleigh wave dispersion curves and ellipticity. They have subsequently been used to model the H/V spectral ratios of noise data from synthetic seismograms, the H/V ratio of S-coda waves based on equipartition theory, and the 3D seismic response of the basin using the spectral element method. General good agreement is found between simulations and observations. The 3D simulation reveals that topography has a much lower contribution to site effects than sedimentary filling, except at the narrow ridge crests. We find clear evidence of a basin edge effect, with an increase of the amplitude of ground motion at some distance from the edge inside the basin and a decrease immediately at the slope foot

Les flux d'azote en élevage de ruminants

L'élevage transforme l'azote des végétaux en produits animaux et en rejette une partie sous forme de déjections, qui peuvent être utilisées comme engrais. Toutefois le développement des productions animales a conduit dans certains territoires à une concentration des apports et rejets d'azote, et une pollution des eaux, du sol et de l'atmosphère. Cette problématique est traitée depuis une vingtaine d'années par les politiques européennes. Que sait-on aujourd'hui de la dynamique des flux d'azote issus des élevages ? Quelles sont les pistes et les échelles pertinentes d'action pour réduire les émissions et leurs impacts sur l'environnement tout en préservant la compétitivité des productions animales ? Ces questions ont motivé de la part des ministères en charge de l'Agriculture et de l'Ecologie, au printemps 2010, une demande d'expertise scientifique collective auprès de l'INRA pour disposer d'un bilan des connaissances sur les différents flux d'azote associés aux activités d'élevage. Nous relatons ici les éléments majeurs concernant l'élevage des ruminants

Interferon Regulatory Factor 8 Regulates Pathways for Antigen Presentation in Myeloid Cells and during Tuberculosis

IRF8 (Interferon Regulatory Factor 8) plays an important role in defenses against intracellular pathogens, including several aspects of myeloid cells function. It is required for ontogeny and maturation of macrophages and dendritic cells, for activation of anti-microbial defenses, and for production of the Th1-polarizing cytokine interleukin-12 (IL-12) in response to interferon gamma (IFNγ) and protection against infection with Mycobacterium tuberculosis. The transcriptional programs and cellular pathways that are regulated by IRF8 in response to IFNγ and that are important for defenses against M. tuberculosis are poorly understood. These were investigated by transcript profiling and chromatin immunoprecipitation on microarrays (ChIP-chip). Studies in primary macrophages identified 368 genes that are regulated by IRF8 in response to IFNγ/CpG and that behave as stably segregating expression signatures (eQTLs) in F2 mice fixed for a wild-type or mutant allele at IRF8. A total of 319 IRF8 binding sites were identified on promoters genome-wide (ChIP-chip) in macrophages treated with IFNγ/CpG, defining a functional G/AGAAnTGAAA motif. An analysis of the genes bearing a functional IRF8 binding site, and showing regulation by IFNγ/CpG in macrophages and/or in M. tuberculosis-infected lungs, revealed a striking enrichment for the pathways of antigen processing and presentation, including multiple structural and enzymatic components of the Class I and Class II MHC (major histocompatibility complex) antigen presentation machinery. Also significantly enriched as IRF8 targets are the group of endomembrane- and phagosome-associated small GTPases of the IRG (immunity-related GTPases) and GBP (guanylate binding proteins) families. These results identify IRF8 as a key regulator of early response pathways in myeloid cells, including phagosome maturation, antigen processing, and antigen presentation by myeloid cells

Amino Acid Availability Controls TRB3 Transcription in Liver through the GCN2/eIF2α/ATF4 Pathway

In mammals, plasma amino acid concentrations are markedly affected by dietary or pathological conditions. It has been well established that amino acids are involved in the control of gene expression. Up to now, all the information concerning the molecular mechanisms involved in the regulation of gene transcription by amino acid availability has been obtained in cultured cell lines. The present study aims to investigate the mechanisms involved in transcriptional activation of the TRB3 gene following amino acid limitation in mice liver. The results show that TRB3 is up-regulated in the liver of mice fed a leucine-deficient diet and that this induction is quickly reversible. Using transient transfection and chromatin immunoprecipitation approaches in hepatoma cells, we report the characterization of a functional Amino Acid Response Element (AARE) in the TRB3 promoter and the binding of ATF4, ATF2 and C/EBPβ to this AARE sequence. We also provide evidence that only the binding of ATF4 to the AARE plays a crucial role in the amino acid-regulated transcription of TRB3. In mouse liver, we demonstrate that the GCN2/eIF2α/ATF4 pathway is essential for the induction of the TRB3 gene transcription in response to a leucine-deficient diet. Therefore, this work establishes for the first time that the molecular mechanisms involved in the regulation of gene transcription by amino acid availability are functional in mouse liver