57 research outputs found

    An atlas of the human liver diurnal transcriptome and its perturbation by hepatitis C virus infection

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    Chronic liver disease and cancer are global health challenges. The role of the circadian clock as a regulator of liver physiology and disease is well established in rodents, however, the identity and epigenetic regulation of rhythmically expressed genes in human disease is less well studied. Here we unravel the rhythmic transcriptome and epigenome of human hepatocytes using male human liver chimeric mice. We identify a large number of rhythmically expressed protein coding genes in human hepatocytes of male chimeric mice, which includes key transcription factors, chromatin modifiers, and critical enzymes. We show that hepatitis C virus (HCV) infection, a major cause of liver disease and cancer, perturbs the transcriptome by altering the rhythmicity of the expression of more than 1000 genes, and affects the epigenome, leading to an activation of critical pathways mediating metabolic alterations, fibrosis, and cancer. HCV-perturbed rhythmic pathways remain dysregulated in patients with advanced liver disease. Collectively, these data support a role for virus-induced perturbation of the hepatic rhythmic transcriptome and pathways in cancer development and may provide opportunities for cancer prevention and biomarkers to predict HCC risk

    Quantitative and predictive model of kinetic regulation by E. coli TPP riboswitches.

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    Riboswitches are non-coding elements upstream or downstream of mRNAs that, upon binding of a specific ligand, regulate transcription and/or translation initiation in bacteria, or alternative splicing in plants and fungi. We have studied thiamine pyrophosphate (TPP) riboswitches regulating translation of thiM operon and transcription and translation of thiC operon in E. coli, and that of THIC in the plant A. thaliana. For all, we ascertained an induced-fit mechanism involving initial binding of the TPP followed by a conformational change leading to a higher-affinity complex. The experimental values obtained for all kinetic and thermodynamic parameters of TPP binding imply that the regulation by A. thaliana riboswitch is governed by mass-action law, whereas it is of kinetic nature for the two bacterial riboswitches. Kinetic regulation requires that the RNA polymerase pauses after synthesis of each riboswitch aptamer to leave time for TPP binding, but only when its concentration is sufficient. A quantitative model of regulation highlighted how the pausing time has to be linked to the kinetic rates of initial TPP binding to obtain an ON/OFF switch in the correct concentration range of TPP. We verified the existence of these pauses and the model prediction on their duration. Our analysis also led to quantitative estimates of the respective efficiency of kinetic and thermodynamic regulations, which shows that kinetically regulated riboswitches react more sharply to concentration variation of their ligand than thermodynamically regulated riboswitches. This rationalizes the interest of kinetic regulation and confirms empirical observations that were obtained by numerical simulations

    What’s retinoic acid got to do with it? Retinoic acid regulation of the neural crest in craniofacial and ocular development

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    Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151310/1/dvg23308.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151310/2/dvg23308_am.pd

    Ageing behavior of polyamide 6-6 parachute fabric in stratosphere and troposphere balloons systems

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    International audienceParachutes are used to recover atmospheric measuring instruments. They are mainly made from polyamide 6-6 fabric. The objective is to identify the change in mechanical and physico-chemical properties of parachute along his lifespan. For this study, a decommissioned parachute has been characterized and compared to a non-used fabric. Results analysis showed a degradation of mechanical properties (tensile strength and tear) and a greater intake of moisture which alter the flight behavior. This is believed to be caused by the change in crystallinity content. The global fabric analysis showed that storage conditions have a significant impact on degradation

    Ageing behavior of polyamide 6-6 parachute fabric in stratosphere and troposphere balloons systems

    No full text
    International audienceParachutes are used to recover atmospheric measuring instruments. They are mainly made from polyamide 6-6 fabric. The objective is to identify the change in mechanical and physico-chemical properties of parachute along his lifespan. For this study, a decommissioned parachute has been characterized and compared to a non-used fabric. Results analysis showed a degradation of mechanical properties (tensile strength and tear) and a greater intake of moisture which alter the flight behavior. This is believed to be caused by the change in crystallinity content. The global fabric analysis showed that storage conditions have a significant impact on degradation

    Dispersion des plantes par les ongulés forestiers

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    National audienceCet article support de la fĂȘte de la Science 2013 dĂ©crit le projet de Recherche DIPLO menĂ© en RĂ©gion centre sur le rĂŽle des ongulĂ©s forestiers dans la dispersion des plantes. Les premiers rĂ©sultats montrent que les ongulĂ©s sont Ă  l'origine de la dispersion dans leur pelage d'au moins une plante sur 7. Sachant que ces espĂšces animales effectuent d'importants trajets journaliers, les ongulĂ©s sauvages sont Ă  mĂȘme de disperser des plantes sur de longues distance
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