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.

/pdf/identification-of-bioactive-metabolites-using-activity-xqhgb7kqo1.pdf

Identification of bioactive metabolites using activity metabolomics

Immunological synapse (IS) formation is a key event during antigen recognition by T cells Recent experimental evidence suggests that the affinity between T cell receptors (TCRs) and antigen is actively modulated during the early steps of TCR signaling In this work, we used an agent-based model to study possible mechanisms for affinity modulation during IS formation We show that, without any specific active mechanism, the observed affinity between receptors and ligands evolves over time, and depends on the density of ligand pMHC (antigen peptide presented by major histocompatibility complexes) and TCR molecules Comparison between the presence or absence of TCR-pMHC centrally directed flow due to F-actin coupling suggest centripetal transport is a potential mechanism for the affinity modulation The model further suggests that the time point of affinity measurement during immune synapse formation is critical Finally, a mathematical model of F-actin foci formation incorporated in the agent-based model, shows that TCR affinity can potentially be actively modulated by a positive/negative feedback of F-actin foci on the TCR-pMHC association rate konCompeting Interest StatementThe authors have declared no competing interestAbbreviationsView Full Text

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Agent-Based Modeling of T Cell Receptor Cooperativity

Comment la surexposition de la region parisienne
a la victimation et a l’insecurite se decline-t-elle dans
la diversite de ses territoires ? Dans le but de repondre
a cette question, notre etude consiste a subdiviser la
region parisienne en unites territoriales caracterisees par
leurs victimations, leur insecurite, leur composition socioprofessionnelle et migratoire et leurs comportements
electoraux. Le croisement de ces donnees produit une
typologie qui confronte les differentes combinaisons de
la victimation et de l’insecurite a la diversite de la composition sociale et politique des territoires en Ile-de-France.

Territoires et insécurité en Île-de-France

Diffuse large B-cell lymphoma is the most common subtype of non-Hodgkin’s lymphoma. It is a germinal center (GC)–derived, aggressive, and heterogeneous disease. Several transcription factors and signaling pathways that play a central role in the progression of the GC reaction and B-cell differentiation have been shown to play an oncogenic role in diffuse large B-cell lymphoma. B-cell lymphoma 6 (BCL6) is a transcriptional repressor that induces the GC B-cell phenotype and blocks plasma cell (PC) differentiation, while interferon regulatory factor 4 (IRF4) and B lymphocyte-induced maturation protein 1 (BLIMP1), a transcriptional promoter, both mediate PC differentiation and exit from the GC (1). Computational models are useful alternatives to trial-and-error experimental investigation. Ordinary differential equation (ODE) models have been used to study different known mechanisms of lymphomagenesis and suggest candidate tumorigenic alterations (2). Furthermore, multi-scale models (MSMs) have been used to study the role of cellular and molecular mechanisms involved in tumor growth (3–6). In this study, we used an existing MSM of PC differentiation in the GC to simulate eight different models with several candidate genetic alterations of the BCL6-IRF4-BLIMP1 regulatory network that lead to transcription factor deregulation and could explain the onset of diffuse large B-cell lymphoma and recapitulate the GC dynamics observed in such conditions. We observed that models with loss of BLIMP1 function (BLIMPloss and BLIMPlossIRFinc) result in an accumulation of B cells in the GC and a block of PC differentiation and thus correctly recapitulate the observed GC and transcription factor dynamics. Models with constitutive activation of the nuclear factor kappa-light-chain-enhancer of activated B-cell (NF-kB) pathway alone and in codominance or co-expression with the enforced BCL6 expression (IRFinc and BCLincIRFinc) result in a decrease of GC B cells and unaltered PC production at early stages of the GC reaction, as observed experimentally. Interestingly, we also found that in IRFinc and BCLincIRFinc models, an increase in PC production could happen at later stages of the GC reaction. Nevertheless, models with enforced BCL6 expression (BCLauto and BCLinc) result in an expansion of GC B cell population and a block in the PC production that was not observed experimentally. Finally, models with loss of IRF4- and BLIMP1-mediated silencing of BCL6 (IRFsil and BLIMPsil) did not affect GC and transcription factor dynamics.

Philippe Robert

Papers

Agent-Based Modeling of T Cell Receptor Cooperativity

Territoires et insécurité en Île-de-France

Multi-Scale Modeling Recapitulates the Effect of Genetic Alterations Associated With Diffuse Large B-Cell Lymphoma in the Germinal Center Dynamics