Role of pattern recognition receptors and microbiota-derived ligands in obesity

Obesity is associated with activation of low-grade inflammation in tissues metabolically relevant for the regulation glucose homeostasis. The gut microbiota has been extensively linked to the inflammatory responses observed during obesity emphasizing the interconnection between host immunity and metabolism during obesity. Gut microbiota together with alteration of the gut barrier functions provide a myriad of circulating ligands for the pattern recognition receptors (PRRs) expressed in innate immune cells and nonimmune cells. PRR-dependent signalling drives the expression of a wide range of genes beyond the inflammatory response depending on the specific functions of the targeted cells and on the physiological context. PRRs activation can have opposite effects on host metabolic inflammation. Nucleotide-binding oligomerization domain 1 (NOD1) or NOD-like Receptor pyrin domain containing 3 (NLRP3) activation promote metabolic inflammation and insulin resistance while NOD2 activation improves insulin sensitivity and glucose homeostasis during obesity. Toll-like receptors (TLRs) 2, 4 and 5 also display specific effects on metabolic tissues. TLR5 deficient mice are prone to obesity and inflammation in response to high fat diet, while injection of TLR5 ligand, flagellin, has a protective effect toward diet-induced obesity. To the opposite TLR2 and 4 activations are associated with deleterious metabolic outcome during obesity. TLR4 activation enhances metabolic inflammation and insulin resistance and TLR2 via its activation by molecules derived from the gut microbiota favours the onset of obesity. It is now clear that activation of PRRs by bacterial derived molecules plays a key role in the host metabolic regulation. PRRs are expressed in various cell types complicating the understanding of the mechanisms underlying the relationship between PRRs activation/silencing and metabolic inflammation in obesity context. This review presents an overview of the current understanding of the interrelationship between the gut microbiota and PRRs, with a focus on its consequences for obesity and related metabolic diseases

Transmembrane protein TMEM230, regulator of metalloproteins and motor proteins in gliomas and gliosis

Glial cells provide physical and chemical support and protection for neurons and for the extracellular compartments of neural tissue through secretion of soluble factors, insoluble scaffolds, and vesicles. Additionally, glial cells have regenerative capacity by remodeling their physical microenvironment and changing physiological properties of diverse cell types in their proximity. Various types of aberrant glial and macrophage cells are associated with human diseases, disorders, and malignancy. We previously demonstrated that transmembrane protein, TMEM230 has tissue revascularization and regenerating capacity by its ability to secrete pro-angiogenic factors and metalloproteinases, inducing endothelial cell sprouting and channel formation. In healthy normal neural tissue, TMEM230 is predominantly expressed in glial and marcophate cells, suggesting a prominent role in neural tissue homeostasis. TMEM230 regulation of the endomembrane system was supported by co-expression with RNASET2 (lysosome, mitochondria, and vesicles) and STEAP family members (Golgi complex). Intracellular trafficking and extracellular secretion of glial cellular components are associated with endocytosis, exocytosis and phagocytosis mediated by motor proteins. Trafficked components include metalloproteins, metalloproteinases, glycans, and glycoconjugate processing and digesting enzymes that function in phagosomes and vesicles to regulate normal neural tissue microenvironment, homeostasis, stress response, and repair following neural tissue injury or degeneration. Aberrantly high sustained levels TMEM230 promotes metalloprotein expression, trafficking and secretion which contribute to tumor associated infiltration and hypervascularization of high tumor grade gliomas. Following injury of the central nervous or peripheral systems, transcient regulated upregulation of TMEM230 promotes tissue wound healing, remodeling and revascularization by activating glial and macrophage generated microchannels/microtubules (referred to as vascular mimicry) and blood vessel sprouting and branching. Our results support that TMEM230 may act as a master regulator of motor protein mediated trafficking and compartmentalization of a large class of metalloproteins in gliomas and gliosis

Array‐Based Seismic Measurements of OSIRIS‐REx's Re‐Entry

The return home of the OSIRIS‐REx spacecraft in September 2023 marked only the fifth time that an artificial object entered the Earth's atmosphere at interplanetary velocities. Although rare, such events serve as valuable analogs for natural meteoroid re‐entries; enabling study of hypersonic dynamics, shock wave generation, and acoustic‐to‐seismic coupling. Here, we report on the signatures recorded by a dense (100 m scale) 11‐station array located almost directly underneath the capsule’s point of peak atmospheric heating in northern Nevada. Seismic data are presented, which allow inferences to be made about the shape of the shock wave’s footprint on the surface, the capsule's trajectory, and its flight parameters

A reference map of the human binary protein interactome.

Global insights into cellular organization and genome function require comprehensive understanding of the interactome networks that mediate genotype-phenotype relationships(1,2). Here we present a human 'all-by-all' reference interactome map of human binary protein interactions, or 'HuRI'. With approximately 53,000 protein-protein interactions, HuRI has approximately four times as many such interactions as there are high-quality curated interactions from small-scale studies. The integration of HuRI with genome(3), transcriptome(4) and proteome(5) data enables cellular function to be studied within most physiological or pathological cellular contexts. We demonstrate the utility of HuRI in identifying the specific subcellular roles of protein-protein interactions. Inferred tissue-specific networks reveal general principles for the formation of cellular context-specific functions and elucidate potential molecular mechanisms that might underlie tissue-specific phenotypes of Mendelian diseases. HuRI is a systematic proteome-wide reference that links genomic variation to phenotypic outcomes

Role of ALPK1 in the development of obesity and associated metabolic diseases

Depuis plusieurs années, l'obésité a pris des proportions épidémiques. Elle est généralement associée à des maladies métaboliques comme les maladies cardiovasculaires et le diabète de type 2. De nombreuses études ont mis en évidence le rôle du microbiote dans la mise en place de l'obésité et dans l'inflammation de bas grade qui s'y installe. Les microorganismes du microbiote possèdent des motifs conservés qui activent les récepteurs de l'immunité innée (PRR). Ces PRRs peuvent avoir un rôle protecteur ou aggravant sur le développement de l'obésité comme cela a été démontré pour certains récepteurs des familles des Toll-like receptors et nucleotid-binding oligomerization domain. La découverte récente d'une nouvelle voie faisant intervenir l'alpha kinase 1 reconnaissant des dérivés d'heptose produit par les bactéries à Gram négatif du microbiote intestinal est intéressante. En effet, l'étude pangénomique du récepteur a révélé que plusieurs polymorphismes du gène codant pour ALPK1 sont associés à la prise de poids et à l'obésité. Le but de cette thèse a été de comprendre le rôle d'ALPK1 dans l'obésité et les maladies métaboliques associées notamment le diabète de type 2. Pour cela, nous avons étudié l'impact de la délétion d'ALPK1 dans un modèle murin en contexte obésogène sur la mise en place de l'obésité et la réponse métabolique de l'hôte. Nous avons montré que la délétion d'ALPK1 induit une diminution de la prise de poids et de l'adiposité en contexte obésogène. Ce phénotype n'était pas lié à une prise énergétique, une absorption des nutriments ou une dépense énergétique altérées. De plus la glycémie à jeun et sa régulation sont améliorées en l'absence d'ALPK1 indépendamment du régime. L'analyse de l'oxydation des lipides et de la réponse métabolique des organes périphériques a permis d'éclaircir les raisons du phénotype observé. En effet, l'absence d'ALPK1 provoque une suractivation du tissu adipeux brun ce qui impacte la capacité thermogénique de ce tissu et le métabolisme énergétique de base. Nos résultats suggèrent une meilleure flexibilité métabolique en l'absence d'ALPK1 au début du régime qui semble prédictive de la prise de poids ensuite. L'ensemble de nos résultats montrent l'importance d'ALPK1 dans la prise de poids et l'intolérance au glucose induites par un régime obésogène et permettra ainsi de cibler cette voie pour potentiellement prévenir et traiter l'obésité.In recent years, obesity has reached epidemic proportions. The pathology is generally associated with non-communicable diseases such as cardiovascular disease, and type 2 diabetes. Numerous studies have highlighted the role of the microbiota in the development of obesity and in the associated low-grade inflammation. The microorganisms that composed the microbiota have conserved motifs that activate the receptors of innate immunity, called pattern recognition receptors (PRRs). Amongst these PRRs, certain receptors in the Toll-like receptor and nucleotide-binding oligomerization domain families can have a protective or aggravating role in the development of obesity. This is why the recent discovery of a new pathway involving alpha kinase 1 (ALPK1) which recognize heptose derivatives produced by Gram-negative bacteria of the intestinal microbiota, is of great interest. Genome-wide association studies of this receptor have shown that several polymorphisms in the gene encoding for ALPK1 are associated with weight gain and obesity. The aim of this thesis was to understand the role of this receptor in obesity and type 2 diabetes. To this end, we studied the impact of ALPK1 deletion in a mouse model in an obesogenic context on the development of obesity and the host metabolic responses. We have shown that ALPK1 deletion induces a reduction in weight gain and adiposity in an obesogenic context. Surprisingly, this phenotype was not associated with altered energy intake, nutrient absorption or energy expenditure. Moreover, fasting glycaemia and its regulation improved in the absence ALPK1, independently of the diet. Differences in lipid oxidation and the metabolic response of peripheral organs explained the phenotype observed. Indeed, the absence of ALPK1 leads to an overactivation of brown adipose tissue, which has an impact on the thermogenic capacity of this tissue and on basal energy metabolism. Our results suggest a greater metabolic flexibility in the absence of ALPK1 at the start of the diet, which appears to be predictive of subsequent weight gain. Taken together, our results demonstrate the importance of ALPK1 in weight gain and glucose intolerance induced by an obesogenic diet and this observation suggest that this pathway might target to potentially prevent and treat obesity and associated diseases

Les titres de périodiques du fonds thématique CeRCA

Source : Photothèque de la MSHS Le Centre de Recherches sur la Cognition et l’Apprentissage (CeRCA) hébergé par la MSHS de Poitiers possède une collection d'ouvrages et de périodiques qui traitent des axes d'étude des 5 équipes de recherche qui la composent, qui sont : les processus d’attention et de contrôle (ATCO) ; les capacités langagières et interactions finalisées (CLIF) ; les structures de mémoire et les processus d’apprentissage et contexte sociocognitif (C2SE) ; la production écrite..

Lire l'état de collection d'une revue

Source : MSHS Le centre de documentation de la Maison des Sciences de l’Homme et de la Société (MSHS) compte actuellement quelque 300 collections de périodiques. Une cinquantaine est encore « vivante » particulièrement dans la section Migrinter. Ce fonds est constitué d'environ 130 titres alimentés par dons, échanges et acquisitions ponctuelles en fonction des programmes de recherche du laboratoire. L’état de collection d’un périodique c’est-à-dire l’ensemble des fascicules présents dans les ..

Les périodiques du fonds spécialisé du FoReLL

Source : Photothèque de la MSHS Le laboratoire FoReLL (FOrmes et REprésentations en Linguistique et Littérature) hébergé par la MSHS de Poitiers est une équipe d'accueil travaillant sur les thèmes de la linguistique et de la littérature. La première équipe composée de linguistes étudie la contrastivité inter-langues, les variations (diachronique, dialectale et synchronique), l’articulation syntaxe / sémantique et la didactique des langues : acquisition, contextes, outils. L'équipe dédiée au t..