Nicotinamide riboside or IL-17A signaling blockers to prevent liver disorders

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Temperature dependent analytical model for submicron GaAs-MESFET

MESFET are used in circuitsof gigahertz frequencies as they are based on gallium arsenide (GaAs) having electron mobility six times higher than that of silicon. An analytical model simulating different device current-voltage characteristics, i.e., output conductance and output transconductance of a 0.3μm gate MESFET with temperature dependence is proposed. The model is validated by comparing the results of the proposed model and those of the numerical simulation. The parameter values are computed using an intrinsic MESFET of two-dimensional geometry. In this work, the distribution of different output loads for varied applied voltages is considered. Simulation results obtainedunder temperature variation effectsfor load distribution and applied driven voltage variation are considered. The RMS and average errors between the different models and GaAs MESFET simulations are calculated to evidence the proposed model accuracy. This was demonstrated by a good agreement between the proposed model and the simulation results, which are found in good agreement. The simulation results obtained under temperature variations were discussed and found to complement those obtained in the literature. This clarifies the relevance of the suggested model analytical

Coxsackievirus B Type 4 Infection in β Cells Downregulates the Chaperone Prefoldin URI to Induce a MODY4-like Diabetes via Pdx1 Silencing.

Enteroviruses are suspected to contribute to insulin-producing β cell loss and hyperglycemia-induced diabetes. However, mechanisms are not fully defined. Here, we show that coxsackievirus B type 4 (CVB4) infection in human islet-engrafted mice and in rat insulinoma cells displays loss of unconventional prefoldin RPB5 interactor (URI) and PDX1, affecting β cell function and identity. Genetic URI ablation in the mouse pancreas causes PDX1 depletion in β cells. Importantly, diabetic PDX1 heterozygous mice overexpressing URI in β cells are more glucose tolerant. Mechanistically, URI loss triggers estrogen receptor nuclear translocation leading to DNA methyltransferase 1 (DNMT1) expression, which induces Pdx1 promoter hypermethylation and silencing. Consequently, demethylating agent procainamide-mediated DNMT1 inhibition reinstates PDX1 expression and protects against diabetes in pancreatic URI-depleted mice . Finally, the β cells of human diabetes patients show correlations between viral protein 1 and URI, PDX1, and DNMT1 levels. URI and DNMT1 expression and PDX1 silencing provide a causal link between enterovirus infection and diabetes.Human diabetic pancreatic samples and data were obtained from the CNIO Biobank thanks to the help of Maria-Jesus Artiga and from Biobanc-Mur, MarBiobank, Vasque Biobank, and Andalusian Public Health System Biobank, integrated in the Spanish Biobank Network and funded by Instituto de Salud Carlos III. We are also thankful to the Biobank of IDIBAPS, Barcelona, for providing samples to A.N. Samples were processed following standard operating procedures with the appropriate approval of the Ethics and Scientific Committees. We also thank the CNIO Mouse Genome Editing Core Unit as well as the CNIO Genomics Unit for their support. We are also thankful to Dr. K. Qvortrup (University of Copenhagen, Denmark) for the electron microscopy. This work was funded by grant to J.P.W. supported by the National Institutes of Health NIAID/NIDDK R01 AI116920, and by grants to N.D. supported by the EFSD/JRDF/Lilly Programme through the European Foundation for the Study of Diabetes (EFSD) and and by the State Research Agency (AEI, 10.13039/501100011033) from the Spanish Ministry of Science and Innovation (projects SAF2016-76598-R, SAF2017-92733-EXP, and RTI2018-094834-B-I00) through the European Regional Development Fund (ERDF). This work was developed at the CNIO, which is funded by the Health Institute Carlos III (ISCIII) and the Spanish Ministry of Science and Innovation.S

Endogenous retroviruses shape pluripotency specification in mouse embryos.

The smooth and precise transition from totipotency to pluripotency is a key process in embryonic development, generating pluripotent stem cells capable of forming all cell types. While endogenous retroviruses (ERVs) are essential for early development, their precise roles in this transition remains mysterious. Using cutting-edge genetic and biochemical techniques in mice, we identify MERVL-gag, a retroviral protein, as a crucial modulator of pluripotent factors OCT4 and SOX2 during lineage specification. MERVL-gag tightly operates with URI, a prefoldin protein that concurs with pluripotency bias in mouse blastomeres, and which is indeed required for totipotency-to-pluripotency transition. Accordingly, URI loss promotes a stable totipotent-like state and embryo arrest at 2C stage. Mechanistically, URI binds and shields OCT4 and SOX2 from proteasome degradation, while MERVL-gag displaces URI from pluripotent factor interaction, causing their degradation. Our findings reveal the symbiotic coevolution of ERVs with their host cells to ensure the smooth and timely progression of early embryo development.acknowledgments: We thank all mouse providers as described in Materials and Methods. We also thank the cniO Animal Facility for mouse maintenance. We acknowledge M. Ko (Keio University, Systems Medicine, Japan) for providing the pZscan4- emerald reporter plasmid. Funding: S.d.l.R. was supported by a fellowship from the comunidad de Madrid and by funds from the Severo Ochoa- cniO. this work was funded by grants to n.d. supported by the State Research Agency (Aei; 10.13039/501100011033) from the Spanish Ministry of Science and innovation (Rti2018- 094834- B- i00 and Pid2021- 122695OB- i00), also including the idiFFeR network of excellence (Red2022- 134792- t), cofunded by european Regional development Fund (eRdF), by the comunidad Autónoma de Madrid (S2017/BMd- 3817), and by the Asociación española contra el cáncer (Aecc) (PRYGn211184dJOU). this work was developed at the cniO funded by the health institute carlos iii (iSciii) and the Spanish Ministry of Science and innovation. Author contributions: S.d.l.R. designed and performed the experiments and analyzed all the data. S.d.l.R. analyzed all the bioinformatics data. M.d.M.R. performed some experiments. P.v. and S.O. performed microinjection in vivo and chimera embryo assay. S.d.l.R and n.d. developed the project and wrote the manuscript. n.d. conceived the project and secured funding. Competing interests:the authors declare that they have no competing interests. Data and materials availability: All data are available in the main text or Materials and Methods. Materials are available upon request to n.d. and the sharing of materials described in this work will be subject to standard material transfer agreementsS

Frasnian conodont abundance and environmental control in northwestern Algerian Sahara

peer reviewedThe conodont abundance and diversity of the Frasnian (Upper Devonian) is analyzed in two well-exposed geological sections, so-called Ben Zireg and South Marhouma of the northwestern Algerian Sahara. The results presented herein show a significant conodont abundance in the Ben Zireg section with 117 elements/kg, which is higher than that observed in the South Marhouma section with only 14 elements/kg. The magnetic susceptibility measurements presented herein may suggest the impact of the terrigenous input on conodont abundance. Indeed, the strata belonging to the middle Frasnian substage in both sections expose higher MS values matching with lower conodont diversity. However, the decrease of the MS signal is correlated with a constant increase in conodont abundance. This new quantitative MS-conodont, revealed by an inverse correlation between MS and conodont abundance, suggesting that MS could potentially serve as a proxy for paleoecological interpretations. The comparison between Ben Zireg and southern Marhouma illustrates the key role of paleogeography in shaping conodont abundance along the stable Gondwana margin. Proximal areas such as Marhouma, located closer to the paleocontinents, were more exposed to elevated detrital input, which likely suppressed conodont proliferation and led to reduced abundance. In contrast, more distal settings like Ben Zireg were exposed to lower terrigenous influx, resulting more optimal ecological conditions that supported higher conodont abundance and diversity

Efficacité d'un procédé membranaire pour le traitement des eaux usées.

Depuis quelques années les gouvernements encouragent les entreprises à trouver de meilleures techniques pour la filtration des eaux usées ou contaminées. La recherche de nouvelles technologies de traitement des eaux plus efficaces et plus écologiques est l'un des plus importants enjeux de notre société moderne, autant sur le plan économique que social. L'eau est de plus en plus polluée et le phénomène d'urbanisation entraîne des quantités d’effluents à traiter qui augmentent sans cesse. Il devient donc nécessaire de trouver une technique qui est à la fois efficace, durable et économiquement rentable. Notre projet consiste à évaluer l’efficacité et la capacité d’un système de filtration membranaire à traiter des effluents industriels et domestiques. La première partie est consacrée à la filtration d’effluents de la Station d’épuration de la Ville de Montréal par des membranes de nano-filtration (Hayka, Montréal). Suite aux filtrations, des tests colorimétriques ont été réalisés, pour déterminer les propriétés physico-chimiques des eaux filtrées. Dans la deuxième partie, des bactéries (Vibrio fischeri), des algues (Pseudokirchneriella subcapitata) et des cellules immunitaires de truite mouchetée (Salvelinus fontinales) ont été exposées aux eaux traitées. L’observation de la viabilité de ces trois espèces a permis d’analyser la toxicité des eaux traitées. De plus l’influence de ces eaux sur la phagocytose chez la truite a été étudiée. D’une part, la membrane fine a éliminé complètement l’azote ammoniacal. D’autre part, aucun effet d’inhibition significatif de la luminescence n’a été observé avec les bactéries V. fischeri exposées aux eaux filtrées par les membranes standard et fine. Enfin, l’eau filtrée par la membrane fine n’a pas affecté la viabilité et la phagocytose des cellules de truites mouchetées, alors que celle traitée par la membrane standard a induit un effet significatif sur la phagocytose

A preliminary mineralogical and physicochemical characterization of the Neogene clays from the Timgad Basin (Massif of Aurès, NE Algeria): potential use in the manufacturing of bricks and ceramic industry

peer reviewedThis study aims at the mineralogical and physicochemical characterization of the clay formations of the Miocene age from the Timgad Basin (Massif of Aurès, NE Algeria), in order to evaluate their possible valorization, notably for their potential use in the manufacturing of bricks and ceramic industry. For this purpose, four samples were taken from a clay-dominated formation that outcrops 5 km east of the Timgad city. Each sample was collected, prepared, and analyzed by the appropriate analytical methods of characterization such as X-ray diffraction, X-ray fluorescence, and scanning electron microscopy. Moreover, other complementary analyses are performed in this study such as laser granulometry and geotechnical tests. The results of the different tests revealed that the clay formations of the Timgad Basin are non-refractory clays and characterized by medium plasticity. These clays are constituted of more than 50% of fine fraction, mainly represented by kaolinite in association with non-negligible proportions of illite, chlorite, mixed-layer clay minerals, and traces of smectite. Besides, this clayey assemblage is accompanied by some proportion of quartz and calcite, as well as traces of hematite, feldspar, and gypsum. In the light of these results and in combination with the particle size distribution, as well as the results of geotechnical tests, it is concluded that the Neogene clays of the Timgad Basin present high limits of Atterberg. Consequently, their use in the field of manufacturing of bricks and terra cotta ‘Terre Cuite’ products is subordinated to a preliminary treatment with addition of a degreasing agent, in the form of coarse sand, in order to improve their plasticity

Diagenesis- and thermal maturity-evolution of the Silurian unconventional hydrocarbon deposits (Tassili n’Ajjer plateau, Algeria): Clay mineralogy, graptolite reflectance, and K–Ar dating

peer reviewedThe need for determining the thermal maturity of Lower Paleozoic rocks has increased with the intensified unconventional shale oil/gas resources exploration within North Africa, Arabian Peninsula, and the adjoining regions. Indeed, Lower Paleozoic strata represent an increasingly important resource that is related to the globally widespread occurrence of graptolite-bearing marine sediments in an expansive shelf area of the Gondwana. However, some crucial information for basin analysis remains poorly understood even across the largest hydrocarbon-producing province in Algeria. The present study provides a solid understanding of the diagenesis- and thermal maturity-evolution from the Tassili n’Ajjer plateau while involving multiple and independent approaches, such as clay mineralogy, petrography, graptolite reflectance, source rock maturity, as well as illite K−Ar geochronology. The combined use of X-ray analysis and field emission scanning electron microscope evidenced kaolinite, illite, and iron-rich chlorite as the main authigenic mineral phases. K−Ar data indicate that episodic in situ illite crystallization occurred at different times, the oldest illite at about 335 Ma and the youngest illite between 238 to 179 Ma, under diagenetic-to-hydrothermal conditions. Paleotemperature estimates (~165–232°C) derived from illite crystallinity (0.37–1.58 Δ°2θ), and graptolite reflectance (VReqv, 1.09–1.84%) values indicate deep diagenetic-low anchizone boundary conditions. This is broadly suggestive of late oil-to-dry gas zones of hydrocarbon generation and destruction, notably in the western sector of the study area. At least two heating events and diagenetic fluid flow processes are identified mainly in response to various tectonic events. They are largely due to fault reactivations, and migration of hot, potassium-rich, fluids throughout the Phanerozoic. Additionally, these events and processes had a later influence on the hydrocarbon maturation, migration, and/or entrapment, especially along the inherited N-S lineaments and Hoggar Massif mega-shear zones in the westernmost part of the Tassili n’Ajjer plateau. Lastly, it is important to highlight that the promising areas offering the highest potential for future unconventional hydrocarbon resource exploration could be most likely those bordering major lineaments, coupled with subsequent igneous activity, where unrestricted hydrothermal fluids are frequently reported, as well as the maturation, being much more advanced.Silurian succession from North Africa - Sedimentology, ichnology and thermal history for a new era of hydrocarbon exploratio