The resurgence of research into cancer metabolism has recently broadened interests beyond glucose and the Warburg effect to other nutrients, including glutamine. Because oncogenic alterations of metabolism render cancer cells addicted to nutrients, pathways involved in glycolysis or glutaminolysis could be exploited for therapeutic purposes. In this Review, we provide an updated overview of glutamine metabolism and its involvement in tumorigenesis in vitro and in vivo, and explore the recent potential applications of basic science discoveries in the clinical setting.

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From Krebs to clinic: glutamine metabolism to cancer therapy.

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Fear of crime : interpreting victimization risk

There have been extensive developments on cellular and molecular mechanisms of immune regulation in allergy, asthma, autoimmune diseases, tumor development, organ transplantation, and chronic infections during the last few years. Better understanding the functions, reciprocal regulation, and counterbalance of subsets of immune and inflammatory cells that interact through interleukins, interferons, TNF-α, and TGF-β offer opportunities for immune interventions and novel treatment modalities in the era of development of biological immune response modifiers particularly targeting these molecules or their receptors. More than 60 cytokines have been designated as interleukins since the initial discoveries of monocyte and lymphocyte interleukins (called IL-1 and IL-2, respectively). Studies of transgenic or gene-deficient mice with altered expression of these cytokines or their receptors and analyses of mutations and polymorphisms in human genes that encode these products have provided essential information about their functions. Here we review recent developments on IL-1 to IL-38, TNF-α, TGF-β, and interferons. We highlight recent advances during the last few years in this area and extensively discuss their cellular sources, targets, receptors, signaling pathways, and roles in immune regulation in patients with allergy and asthma and other inflammatory diseases.

Interleukins (from IL-1 to IL-38), interferons, transforming growth factor β, and TNF-α: Receptors, functions, and roles in diseases

Loss of Bcl-6-Expressing T Follicular Helper Cells and Germinal Centers in COVID-19.

The metabolome, the collection of small-molecule chemical entities involved in metabolism, has traditionally been studied with the aim of identifying biomarkers in the diagnosis and prediction of disease. However, the value of metabolome analysis (metabolomics) has been redefined from a simple biomarker identification tool to a technology for the discovery of active drivers of biological processes. It is now clear that the metabolome affects cellular physiology through modulation of other 'omics' levels, including the genome, epigenome, transcriptome and proteome. In this Review, we focus on recent progress in using metabolomics to understand how the metabolome influences other omics and, by extension, to reveal the active role of metabolites in physiology and disease. This concept of utilizing metabolomics to perform activity screens to identify biologically active metabolites - which we term activity metabolomics - is already having a broad impact on biology.

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Identification of bioactive metabolites using activity metabolomics

Integrin and small immunoglobulin superfamily (sIGSF) adhesion complexes function physiologically in human immunological synapses (IS) wherein sIGSF complexes form a corolla of microdomains around an integrin ring and secretory core. The corolla recruits and retains the major costimulatory and checkpoint complexes that regulate the response to T cell receptor (TCR) engagement, making forces that govern corolla formation of particular interest. We developed a phenomenological agent-based model in order to test different hypotheses concerning the mechanisms underlying molecular reorganization during IS formation. The model showed that sIGSF complexes are passively excluded to the distal aspect of the IS as long as their interaction with the ramified F-actin transport network is absent or weaker than that of integrins. An attractive force between sIGSF adhesion and costimulatory/checkpoint complexes relocates the latter from the centre of the IS to the corolla. The simulations suggest that size based sorting interactions with large glycocalyx components as well as a short-range self-attraction between sIGSF complexes explain the corolla “petals”. These molecular and mechanistic features establish a general model that can recapitulate complex pattern formation processes observed in cell-bilayer and cell-cell interfaces. One Sentence Summary Computer simulations of immunological synapses reveal the localization mechanisms of immunoglobulin superfamily adhesion and costimulatory/checkpoint complexes.

/pdf/in-silico-characterization-of-mechanisms-positioning-1oxon865tl.pdf

In silico characterization of mechanisms positioning costimulatory and checkpoint complexes in immune synapses

Jalon pour une histoire de la statistique judiciaire

Dans le cadre du groupe d'exploitation des enquetes Cadre de vie et securite (ci-apres CVS), l'INSEE a, par conventions 2008/00031 et 2009/00001, mis a la disposition du CESDIP les enquetes 2007 et 2008 Les travaux que nous devions realiser sur ces donnees – notamment la preparation d'articles pour Economie et Statistique sur le raccordement de ces deux enquetes aux donnees anterieures sur la victimation ou encore les profils de victimes – nous ont obliges a mener prealablement a bien leur exploitation systematique, d'autant qu'il s'agissait d'un dispositif nouveau Afin de mettre ce travail largement a disposition, nous lui avons donne la forme d'un rapport de recherche en ligne

https://hal.archives-ouvertes.fr/hal-00521994/document

Cadre de vie et sécurité

Dans le cadre du groupe d'exploitation des enquetes Cadre de vie et securite (ci-apres CVS), l'INSEE a, par conventions 2008/00031 et 2009/00001, mis a la disposition du CESDIP les enquetes 2007 et 2008. Les travaux que nous devions realiser sur ces donnees – notamment la preparation d'articles pour Economie et Statistique sur le raccordement de ces deux enquetes aux donnees anterieures sur la victimation ou encore les profils de victimes – nous ont obliges a mener prealablement a bien leur exploitation systematique, d'autant qu'il s'agissait d'un dispositif nouveau. Afin de mettre ce travail largement a disposition, nous lui avons donne la forme d'un rapport de recherche en ligne.

Philippe Robert

Papers

In silico characterization of mechanisms positioning costimulatory and checkpoint complexes in immune synapses

Jalon pour une histoire de la statistique judiciaire

Cadre de vie et sécurité

Cadre de vie et sécurité: Analyse des enquêtes pour 2005-2006 et 2006-2007

Victimation et insécurité en Île-de-France, 2002-2003-2004. Analyse de la 3e enquête (2005)