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

Foxp3+ regulatory T (Treg) cells, which are crucial for maintenance of self-tolerance, mainly develop within the thymus, where they arise from CD25+Foxp3− or CD25−Foxp3+ Treg cell precursors. Although it is known that infections can cause transient thymic involution, the impact of infection-induced thymus atrophy on thymic Treg (tTreg) cell development is unknown. Here, we infected mice with influenza A virus (IAV) and studied thymocyte population dynamics post infection. IAV infection caused a massive, but transient thymic involution, dominated by a loss of CD4+CD8+ double-positive (DP) thymocytes, which was accompanied by a significant increase in the frequency of CD25+Foxp3+ tTreg cells. Differential apoptosis susceptibility could be experimentally excluded as a reason for the relative tTreg cell increase, and mathematical modeling suggested that enhanced tTreg cell generation cannot explain the increased frequency of tTreg cells. Yet, an increased death of DP thymocytes and augmented exit of single-positive (SP) thymocytes was suggested to be causative. Interestingly, IAV-induced thymus atrophy resulted in a significantly reduced T cell receptor (TCR) repertoire diversity of newly produced tTreg cells. Taken together, IAV-induced thymus atrophy is substantially altering the dynamics of major thymocyte populations, finally resulting in a relative increase of tTreg cells with an altered TCR repertoire.

https://www.biorxiv.org/content/biorxiv/early/2020/09/16/2020.09.09.274795.full.pdf

Influenza A virus-induced thymus atrophy differentially affects dynamics of conventional and regulatory T cell development

Les enquêtes sur la victimation et l'insécurité en Europe

CTLA4 is an essential negative regulator of T cell immune responses and is a key checkpoint regulating autoimmunity and anti-tumour immunity. Genetic mutations resulting in a quantitative defect in CTLA4 are associated with the development of an immune dysregulation syndrome. Endocytosis of CTLA4 is rapid and continuous with subsequent degradation or recycling. CTLA4 has two natural ligands, the surface transmembrane proteins CD80 and CD86 that are shared with the T cell co-stimulatory receptor CD28. Upon ligation with CD80/CD86, CTLA4 can remove these ligands from the opposing cells by transendocytosis. The efficiency of ligand removal is thought to be highly dependent on the processes involved in CTLA4 trafficking. With a combined in vitro-in silico study, we quantify the rates of CTLA4 internalization, recycling and degradation. We incorporate experimental data from cell lines and primary human T cells. Our model provides a framework for exploring the impact of altered affinity of natural ligands or therapeutic anti-CTLA4 antibodies and for predicting the effect of clinically relevant CTLA4 pathway mutations. The presented methodology for extracting trafficking rates can be transferred to the study of other transmembrane proteins.

/pdf/quantitative-characterization-of-ctla4-trafficking-and-3ooj3do7tl.pdf

Quantitative characterization of CTLA4 trafficking and turnover using a combined in vitro and in silico approach

On pourrait distinguer deux âges epistemologiques de la mesure du crime : celui ou elle se reduit aux denombrements de l'activite judiciaire et celui ou d'autres sources entrent en competition. Le premier apparait dans l'Europe de la deuxieme partie du XVIIIe siecle et se developpe au siecle suivant : des sa naissance, la statistique des tribunaux est aussi utilisee, malgre quelques hesitations, pour mesurer la delinquance et a travers elle l'etat moral de la nation. Au cours du XXe siecle, la statistique policiere remplacera, plus ou moins vite selon les pays, celle des tribunaux comme mesure de la delinquance. Dans la deuxieme partie de ce siecle, on aura progressivement recours a d'autres mesures ; la plus typique est l'enquete de victimation dont les auteurs racontent le developpement. A travers le probleme tres technique de la mesure de la delinquance, on voit defiler et les problemes methodologiques d'une sociologie quantitative et aussi toutes les questions conceptuelles que lui pose l'etude du crime.

https://hal.archives-ouvertes.fr/hal-00743138/document

Statistique criminelle et mesure de la délinquance

This article presents some preliminary results of the first French national victimization survey. Investigations into victimization are mainly used in France to determine the social profile of victims, as well as their behaviour and attitudes. The survey was implemented in two phases: a screening question on a national sample of 11,000, followed in the second phase by 1,049 victims answering a detailed questionnaire on their attitudes and behaviour. Besides ordinary property and personal offences, family violence and offences related to consumption and business life were included. For each of those types of victimization, the authors detail the specific socio-demographic characteristics of victims in order to compare these profiles. Finally they present data on the consequences of victimization and on the different resources to which victims turn.These results are used to document a discussion on criminal policy issues; in particular, passivity of the police confronted with individual complaints against u...

Philippe Robert

Papers

Influenza A virus-induced thymus atrophy differentially affects dynamics of conventional and regulatory T cell development

Les enquêtes sur la victimation et l'insécurité en Europe

Quantitative characterization of CTLA4 trafficking and turnover using a combined in vitro and in silico approach

Statistique criminelle et mesure de la délinquance

Victims as Actors of Social Control: An Empirical Inquiry in France and Some Implications