Neurobiology of Inflammation-Associated Anorexia

Compelling data demonstrate that inflammation-associated anorexia directly results from the action of pro-inflammatory factors, primarily cytokines and prostaglandins E2, on the nervous system. For instance, the aforementioned pro-inflammatory factors can stimulate the activity of peripheral sensory neurons, and induce their own de novo synthesis and release into the brain parenchyma and cerebrospinal fluid. Ultimately, it results in the mobilization of a specific neural circuit that shuts down appetite. The present article describes the different cell groups and neurotransmitters involved in inflammation-associated anorexia and examines how they interact with neural systems regulating feeding such as the melanocortin system. A better understanding of the neurobiological mechanisms underlying inflammation-associated anorexia will help to develop appetite stimulants for cancer and AIDS patients

Vers de nouvelles matrices minérales pour l'immobilisation et la valorisation des déchets ultimes de l'incinération des déchets ménagers

L'objectif général de cette thèse est de transformer les déchets ultimes et dangereux contenant des métaux lourds, en matières minérales chimiquement stables. L'augmentation de la production des ordures ménagères (OM) est un problème qui concerne et préoccupe le monde entier. Parmi les différentes méthodes de traitement des déchets municipaux, l'incinération est une technologie qui peut fournir une solution efficace et respectueuse pour l'environnement. Le problème de ce traitement est la production de REFIOM. Les REFIOM peuvent contenir de grandes quantités de composés métalliques toxiques et est considéré comme un déchet dangereux ce qui oblige à les mettre en décharges classées. Trois types de matériaux pour l'immobilisation du plomb et du cadmium ont été étudiés : les vitrocéramiques, les céramiques frittées et les géopolymères. Nous sommes parvenus à synthétiser une base de vitrocéramique à partir de cendres incinérées purs et nous avons diminué sa volatilisation lors de sa production. Des résultats prometteurs ont été obtenus pour la vitrocéramique Ca-Mg-Si-O qui a incorporé durablement une quantité élevée de cadmium dans les structures cristallines et le plomb dans la structure amorphe. La phase cristalline est plus résistante à l'attaque acide en raison de son incorporation dans une matrice vitreuse qui génère une double protection. Ses travaux ouvrent la possibilité de créer cette matrice en ajoutant des oxydes commerciaux aux résidus d'incinération. Nous avons étudié la céramique frittée à base du système Ba-Mg-Ti-O. Nous avons obtenu les trois phases minérales présentées dans la céramique SYNROC (hollandite, pérovskite et rutile) où le cadmium substitue le magnésium tandis que le plomb a occupé le site appartenant au baryum. La céramique frittée est satisfaisante en termes d'immobilisation des métaux lourds avec de bonnes propriétés physiques. Pour produire des géopolymères résistants à partir de REFIOM, il est avantageux d'utiliser un rapport L/S = 1,2 et de les sécher à température ambiante. Il a été observé que le frittage influence le taux de réorganisation structurelle avec l'apparition de la phase sodalite ( Na4Si3Al3O12Cl), qui se compose de tunnels où les métaux lourds peuvent être incorporés. Le plomb et le cadmium restent largement en dessous de la limite des normes TCLP. Le traitement thermique à plus de 500C augmente la densité de l'échantillon. Lorsque les REFIOM sont mélangés avec d'autres types de déchets tels que des MIOM ou du calcin, il est possible d'augmenter la résistance chimique et mécanique. Nous avons conclu que les trois matrices de stockages étudiées offrent de bonne perspective pour l'immobilisation du plomb et du cadmiumThe overall objective of this thesis is to transform ultimate and hazardous waste containing heavy metals, into chemically stable mineral materials. The increasing municipal solid waste (MSW) generation is a problem ranging to global concern. Among various MSW treatment methods, incineration is a technology, which may provide an efficient and environmental friendly solution. Problem of this treatment is the production of fly ash. Fly ash may contain large amounts of toxic metal compounds and is considered as hazardous waste with obligation of final disposal into specialized landfills. Three types of materials for immobilization of lead and cadmium have been investigated: glass ceramics, sintered ceramics and geopolymers. We manage to synthetize a glass-ceramic based purely on the incinerated ashes and to decrease the volatilization during its production. Promising results have been obtained for Ca-Mg-Si-O bearing glass-ceramic with high sustainable incorporation of cadmium into crystalline structures and lead into an amorphous structure. Crystalline structure was evaluated being more resistant against acid attack because of its embedding into a glass matrix that generates a double protection. The future research should be done on possibility obtaining this phase by addition of commercial oxides into fly ash. Sintered ceramic investigated was based on Ba-Mg-Ti-O system. We obtained three mineral phases presented in SYNROC (hollandite, perovskite and rutile) where cadmium substituted the site of magnesium while lead occupied the site belonging to barium. The sintered ceramic is satisfactory in terms of toxic elements incorporation and of chemical and mechanical resistance. For production of resistant geopolymer from fly ashes, it is favorable to use ratio L/S =1.2 and drying at room temperature. It was observed that sintering affects the rate of structural reorganization with apparition of sodalite phase (Na4Si3Al3O12Cl), which consists of tunnels where heavy metals can be incorporated. Lead and cadmium stay mainly below the limit of TCLP standards. The heat treatment over 500C increases density of the sample. When fly ash mixed with other types of waste such as bottom ash or waste glass powder, it is possible to obtain a more resistant. It was found that all three matrices are a good prospect for a stabilization technique with respect to the major pollutants lead (Pb) and cadmium (Cd)PARIS-EST-Université (770839901) / SudocSudocFranceF

Profiling of G protein-coupled receptors in vagal afferents reveals novel gut-to-brain sensing mechanisms

Objectives: G protein-coupled receptors (GPCRs) act as transmembrane molecular sensors of neurotransmitters, hormones, nutrients, and metabolites. Because unmyelinated vagal afferents richly innervate the gastrointestinal mucosa, gut-derived molecules may directly modulate the activity of vagal afferents through GPCRs. However, the types of GPCRs expressed in vagal afferents are largely unknown. Here, we determined the expression profile of all GPCRs expressed in vagal afferents of the mouse, with a special emphasis on those innervating the gastrointestinal tract. Methods: Using a combination of high-throughput quantitative PCR, RNA sequencing, and in situ hybridization, we systematically quantified GPCRs expressed in vagal unmyelinated Nav1.8-expressing afferents. Results: GPCRs for gut hormones that were the most enriched in Nav1.8-expressing vagal unmyelinated afferents included NTSR1, NPY2R, CCK1R, and to a lesser extent, GLP1R, but not GHSR and GIPR. Interestingly, both GLP1R and NPY2R were coexpressed with CCK1R. In contrast, NTSR1 was coexpressed with GPR65, a marker preferentially enriched in intestinal mucosal afferents. Only few microbiome-derived metabolite sensors such as GPR35 and, to a lesser extent, GPR119 and CaSR were identified in the Nav1.8-expressing vagal afferents. GPCRs involved in lipid sensing and inflammation (e.g. CB1R, CYSLTR2, PTGER4), and neurotransmitters signaling (CHRM4, DRD2, CRHR2) were also highly enriched in Nav1.8-expressing neurons. Finally, we identified 21 orphan GPCRs with unknown functions in vagal afferents. Conclusion: Overall, this study provides a comprehensive description of GPCR-dependent sensing mechanisms in vagal afferents, including novel coexpression patterns, and conceivably coaction of key receptors for gut-derived molecules involved in gut-brain communication. Keywords: G protein-coupled receptors, Vagal afferent nerves, Gut-brain axis, Gut hormones, GLP1R, NTSR

A Cardiac MicroRNA Governs Systemic Energy Homeostasis by Regulation of MED13

SummaryObesity, type 2 diabetes, and heart failure are associated with aberrant cardiac metabolism. We show that the heart regulates systemic energy homeostasis via MED13, a subunit of the Mediator complex, which controls transcription by thyroid hormone and other nuclear hormone receptors. MED13, in turn, is negatively regulated by a heart-specific microRNA, miR-208a. Cardiac-specific overexpression of MED13 or pharmacologic inhibition of miR-208a in mice confers resistance to high-fat diet-induced obesity and improves systemic insulin sensitivity and glucose tolerance. Conversely, genetic deletion of MED13 specifically in cardiomyocytes enhances obesity in response to high-fat diet and exacerbates metabolic syndrome. The metabolic actions of MED13 result from increased energy expenditure and regulation of numerous genes involved in energy balance in the heart. These findings reveal a role of the heart in systemic metabolic control and point to MED13 and miR-208a as potential therapeutic targets for metabolic disorders.PaperCli

Tissue Resources for the Functional Annotation of Animal Genomes

In order to generate an atlas of the functional elements driving genome expression in domestic animals, the Functional Annotation of Animal Genome (FAANG) strategy was to sample many tissues from a few animals of different species, sexes, ages, and production stages. This article presents the collection of tissue samples for four species produced by two pilot projects, at INRAE (National Research Institute for Agriculture, Food and Environment) and the University of California, Davis. There were three mammals (cattle, goat, and pig) and one bird (chicken). It describes the metadata characterizing these reference sets (1) for animals with origin and selection history, physiological status, and environmental conditions; (2) for samples with collection site and tissue/cell processing; (3) for quality control; and (4) for storage and further distribution. Three sets are identified: set 1 comprises tissues for which collection can be standardized and for which representative aliquots can be easily distributed (liver, spleen, lung, heart, fat depot, skin, muscle, and peripheral blood mononuclear cells); set 2 comprises tissues requiring special protocols because of their cellular heterogeneity (brain, digestive tract, secretory organs, gonads and gametes, reproductive tract, immune tissues, cartilage); set 3 comprises specific cell preparations (immune cells, tracheal epithelial cells). Dedicated sampling protocols were established and uploaded in https://data.faang.org/protocol/samples. Specificities between mammals and chicken are described when relevant. A total of 73 different tissues or tissue sections were collected, and 21 are common to the four species. Having a common set of tissues will facilitate the transfer of knowledge within and between species and will contribute to decrease animal experimentation. Combining data on the same samples will facilitate data integration. Quality control was performed on some tissues with RNA extraction and RNA quality control. More than 5,000 samples have been stored with unique identifiers, and more than 4,000 were uploaded onto the Biosamples database, provided that standard ontologies were available to describe the sample. Many tissues have already been used to implement FAANG assays, with published results. All samples are available without restriction for further assays. The requesting procedure is described. Members of FAANG are encouraged to apply a range of molecular assays to characterize the functional status of collected samples and share their results, in line with the FAIR (Findable, Accessible, Interoperable, and Reusable) data principles

Minéralogie physique de phases silicatées alumino-calciques du manteau terrestre. Implications géodynamiques

Mineral physics could provide answers to many questions we asked about mineral phases present in the Earth's mantle, their characteristics, their crystal structure, their phase transitions. In the second part of the twentieth century, high pressure and high temperature experiments could give essential informations about materials from the deep Earth: these data could then be combined to those obtained by seismology measurements, geochemistry analyses, experimental and theoretical geodynamics, for a better understanding of the deep parts of our planet. Many former studies revealed that silicate phases bearing calcium and/or aluminium could display very interesting characteristics and properties, with important geodynamics implications. The combination of calcium and aluminium is know to be very useful for mineral phases: indeed, calcium is able to be substituted by atoms which display large cations, while aluminium when replacing silicon atoms could allow the eventual charge compensation required by the substitution of calcium. Moreover, there is an increasing amount of data which reveal the existence of many new (Ca,Al)-rich silicate phases at (P,T) conditions of the Earth's mantle: these phase are found to display very original structure and properties. In this thesis manuscript, we report the main results obtained about the aluminous calcium perovskite, Al-CaSiO3, which is one of the three main mineral phases present in the lower mantle. We show that this phase is able to incorporate huge amount of natural actinides uranium and thorium which provide the main part of the heat produced in our planet, by radioactive decay. Then the Al-rich Ca-perovskite bearing U and Th could be the thermal engine of the Earth's lower mantle. These results obtained by mineral physics experiments and methodology are presented with the objective to better constrain the recent geodynamics models. Here, we propose that the (U,Th)-Al-CaSiO3 perovskite alone is able to provide the entire bottom heating of the big domes observed in the cross sections of the mantle obtained by seismic tomography. The possible relation between our results from mineral physics and the volume of "hot" materials present at the bottom of the mantle, is also discussed. The second silicate phase bearing Ca and Al presented in this thesis is the new high pressure phase named CAS phase of composition CaAl4Si2O11. After many experimental studies performed at high pressure on basaltic crust assemblage, it is now commonly accepted that the CAS phase is one of the main mineral phases present in the oceanic crust (Mid-Ocean Ridge Basalt, MORB) subducted to the lowermost lower mantle. The CAS phase is shown to be one of the last solid residual phases (with Ca-perovskite) when the oceanic crust is partially molten, as expected when this crust reaches the D'' region. Here, we show that the CAS phase bears an isosymmetrical transition where some silicon atoms adopt a coordination 5, in the trigonal bipyramidal site (2 face-sharing tetraedra). The implications of such intermediate coordination (between coordinations 4 and 6) is discussed in terms of diffusion processes, diffusion creep deformation, viscosity: it appears that the formation of SiO5 groups strongly favours the deformation properties of these materials, and then enhances their transport properties. It is clear that the coordination of silicon atoms could have a strong direct effect on the dynamic processes occurring in the deep mantle. With the two studies presented in this thesis, we see that experimental mineral physics can provide essential data for models in geodynamics, thermal behaviour and in seismology. Seismic waves give informations about the structure of the deep Earth and the density profile, while experimental geodynamics reproduce the rheological behaviour of the mantle with appropriate fluids and a bottom heating: it is then important to provide complementary data about the Earth materials. The study of the CAS phase shows that the macroscopic properties of the mantle could find their origin in the microscopic structure of the Earth's mineral phases.La minéralogie physique a permis d'élucider de nombreuses énigmes relatives aux phases minérales du manteau terrestre, leur nature, leur changement de phase. L'expérimentation à haute pression et haute température dans la seconde moitié du 20ème siècle a permis d'apporter des données essentielles sur les matériaux du globe : on a pu alors faire le lien entre ces matériaux et les données obtenues par la sismologie, la géochimie et la géodynamique notamment. Les phases silicatées riches en calcium et aluminium se révèlent avoir des caractéristiques particulièrement intéressantes, avec de grandes implications géodynamiques. L'intérêt majeur de la combinaison de ces deux éléments est que le calcium peut être substitué par des cations volumineux tandis que l'aluminium permet d'assurer les compensations de charges en se substituant au silicium. D'autre part, la minéralogie de Ca et Al est caractérisée par de nombreuses nouvelles phases aux propriétés et structures tout à fait originales. Nous présentons ici les principaux résultats obtenus sur la perovskite calcique alumineuse Al-CaSiO3 : cette phase est capable d'incorporer de très grandes quantités d'actinides uranium et thorium, qui sont les principales sources d'énergie du globe. Ainsi cette phase minérale peut être le véritable moteur thermique du manteau inférieur terrestre. Ces résultats sont énoncés dans la perspective de mieux contraindre les modèles géodynamiques récents : ainsi cette phase pourrait à elle seule contribuer au chauffage par le bas de gros dômes observés dans les coupes du manteau obtenues par tomographie sismique. La relation possible entre nos résultats de minéralogie physique et le volume de matériaux chauds dans le bas du manteau terrestre est également discutée. La deuxième phase alumino-calcique présentée ici est la nouvelle phase appelée CAS et de composition CaAl4Si2O11. Il est maintenant acquis que ce minéral est essentiel dans les basaltes en subduction, notamment lorsqu'ils sont partiellement fondus. Mais plus intéressant, nous montrons que cette phase est caractérisée par une transition isosymétrique permettant à des atomes de silicium d'adopter une coordinence 5 au sein d'une bipyramide trigonale (2 tétraèdres partageant une face). L'importance d'une telle coordinence pour Si, intermédiaire entre les coordinences 4 et 6, est discutée, notamment en termes de processus de diffusion, de déformation par fluage diffusionnel, de viscosité : il apparaît clairement que des espèces telles que les groupes SiO5 favorisent grandement la déformation des matériaux qui les contiennent, et contribuent donc à améliorer leurs propriétés de transport. Ainsi la coordinence du silicium a un effet direct sur les processus dynamiques se produisant dans le manteau profond. A travers ces deux grandes études, on s'aperçoit à quel point les résultats de minéralogie physique peuvent apporter des données essentielles permettant d'alimenter des modèles géodynamiques, des modèles de fonctionnement thermique ou des modèles sismologiques. La sismologie ausculte le globe dans sa totalité, les expériences de géodynamique en laboratoire simulent le comportement rhéologiques du manteau avec des fluides et un chauffage par le bas : il est important d'apporter à ces modèles des informations précises sur les matériaux traversés par les ondes sismiques, ou que l'on essaie de modéliser en dynamique. D'autre part, l'étude de la phase CAS montre que des propriétés macroscopiques observées dans le manteau terrestre peuvent trouver leur origine dans la structure microscopique des phases minérales du manteau

Spiridion Kanellis, un plagiaire audacieux du XIX

En 1883, un cas de plagiat qualifié d’audacieux était révélé lors d’une séance de la Société de biologie de Paris. Cet article discute les détails de ce plagiat et l’identité de son auteur, un médecin du nom de Spiridion Kanellis