Succinate receptor in GtoPdb v.2021.3

Nomenclature as recommended by NC-IUPHAR [8]. The Succinate receptor was identified as being activated by physiological levels of the Kreb's cycle intermediate succinate and other dicarboxylic acids such as maleate in 2004. Since its pairing with its endogenous ligand, the receptor has been the focus of intensive research and its role has been evidenced in various (patho)physiological processes such as regulation of renin production, retinal angiogenesis, inflammation or the immune response

Succinate receptor in GtoPdb v.2023.1

Nomenclature as recommended by NC-IUPHAR [8]. The succinate receptor (GPR91, SUCNR1) is activated by the tricarboxylic acid (or Krebs) cycle intermediate succinate and other dicarboxylic acids with less clear physiological relevance such as maleate [17]. Since its pairing with its endogenous ligand in 2004, intense research has focused on the receptor-ligand pair role in various (patho)physiological processes such as regulation of renin production [17, 39], ischemia injury [17], fibrosis [25], retinal angiogenesis [34], inflammation [25, 23], immune response [32], obesity [44, 26, 21], diabetes [42, 22, 39], platelet aggregation [38, 36] or cancer [28, 46]. The succinate receptor is coupled to Gi/o [11, 17] and Gq/11 protein families [31, 17, 40]. Although the receptor is, upon ligand addition, rapidly desensitized [19, 31], and in some cells internalized [17], it seems to recruit arrestins weakly [10]. The cellular activation of the succinate receptor triggers various signalling pathways such as decrease of cAMP levels, [Ca2+]i mobilization and activation of kinases (ERK, c-Jun, Akt, Src, p38, PI3Kβ, etc.) [12]. The receptor is broadly expressed but is notably abundant in immune cells (M2 macrophages [40, 21], monocytes [32], immature dendritic cells [32], adipocytes [44], platelets [38, 36], etc.) and in the kidney [17]

Succinate receptor (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

Nomenclature as recommended by NC-IUPHAR [7]. The Succinate receptor has been identified as being activated by physiological levels of the Kreb's cycle intermediate succinate and other dicarboxylic acids such as maleate in 2004. Since its pairing with its endogenous ligand, the receptor has been the focus of intensive research and its role has been evidenced in various (patho)physiological processes such as regulation of renin production, retinal angiogenesis, inflammation or immune response

The shape of the CMB lensing bispectrum

Lensing of the CMB generates a significant bispectrum, which should be detected by the Planck satellite at the 5-sigma level and is potentially a non-negligible source of bias for f_NL estimators of local non-Gaussianity. We extend current understanding of the lensing bispectrum in several directions: (1) we perform a non-perturbative calculation of the lensing bispectrum which is ~10% more accurate than previous, first-order calculations; (2) we demonstrate how to incorporate the signal variance of the lensing bispectrum into estimates of its amplitude, providing a good analytical explanation for previous Monte-Carlo results; and (3) we discover the existence of a significant lensing bispectrum in polarization, due to a previously-unnoticed correlation between the lensing potential and E-polarization as large as 30% at low multipoles. We use this improved understanding of the lensing bispectra to re-evaluate Fisher-matrix predictions, both for Planck and cosmic variance limited data. We confirm that the non-negligible lensing-induced bias for estimation of local non-Gaussianity should be robustly treatable, and will only inflate f_NL error bars by a few percent over predictions where lensing effects are completely ignored (but note that lensing must still be accounted for to obtain unbiased constraints). We also show that the detection significance for the lensing bispectrum itself is ultimately limited to 9 sigma by cosmic variance. The tools that we develop for non-perturbative calculation of the lensing bispectrum are directly relevant to other calculations, and we give an explicit construction of a simple non-perturbative quadratic estimator for the lensing potential and relate its cross-correlation power spectrum to the bispectrum. Our numerical codes are publicly available as part of CAMB and LensPix.Comment: 32 pages, 10 figures; minor changes to match JCAP-accepted version. CMB lensing and primordial local bispectrum codes available as part of CAMB (http://camb.info/

From College To Jobs: Making Sense of Labor Market Returns To Higher Education

This report summarizes key findings from recent research on links between higher education and the workforce. Featuring eight brief papers from leading education and workforce experts from around the country, the report offers practical advice for institutional leaders, policymakers, students and their advisers about how to use the increasingly available information on the economic value of higher education. Specifically, the authors' papers and the opening summary explore what various audiences can learn from emerging evidence about: variations in labor market outcomes by program and institution; the value of degrees to jobs both in and out of fields studied; returns to the completion of certain course clusters that don't add up to a degree; and distortions that may result from examining returns to individual degrees rather than "stacked" degrees

Paracellular permeability is increased by basal lipopolysaccharide in a primary culture of colonic epithelial cells; an effect prevented by an activator of Toll-like receptor-2

Lipopolysaccharide (LPS), which generally activates Toll-like receptor 4 (TLR4), is expressed on commensal colonic bacteria. In a number of tissues, LPS can act directly on epithelial cells to increase paracellular permeability. Such an effect in the colon would have an important impact on the understanding of normal homeostasis and of pathology. Our aim was to use a novel primary culture of colonic epithelial cells grown on Transwells to investigate whether LPS, or Pam(3)CSK( 4), an activator of TLR2, affected paracellular permeability. Consequently, [(14)C]-mannitol transfer and transepithelial electrical resistance (TEER) were measured. The preparation consisted primarily of cytokeratin-18 positive epithelial cells that produced superoxide, stained for mucus with periodic acid-Schiff reagent, exhibited alkaline phosphatase activity and expressed TLR2 and TLR4. Tight junctions and desmosomes were visible by transmission electron microscopy. Basally, but not apically, applied LPS from Escherichia coli increased the permeability to mannitol and to a 10-kDa dextran, and reduced TEER. The LPS from Helicobacter pylori increased paracellular permeability of gastric cells when applied either apically or basally, in contrast to colon cells, where this LPS was active only from the basal aspect. A pan-caspase inhibitor prevented the increase in caspase activity caused by basal E. coli LPS, and reduced the effects of LPS on paracellular permeability. Synthetic Pam(3)CSK(4) in the basal compartment prevented all effects of basal E. coli LPS. In conclusion, LPS applied to the base of the colonic epithelial cells increased paracellular permeability by a mechanism involving caspase activation, suggesting a process by which perturbation of the gut barrier could be exacerbated. Moreover, activation of TLR2 ameliorated such effects

Comprehensive ecosystem model-data synthesis using multiple data sets at two temperate forest free-air CO2 enrichment experiments: Model performance at ambient CO2 concentration

Free-air CO2 enrichment (FACE) experiments provide a remarkable wealth of data which can be used to evaluate and improve terrestrial ecosystem models (TEMs). In the FACE model-data synthesis project, 11 TEMs were applied to two decadelong FACE experiments in temperate forests of the southeastern U.S.—the evergreen Duke Forest and the deciduous Oak Ridge Forest. In this baseline paper, we demonstrate our approach to model-data synthesis by evaluating the models' ability to reproduce observed net primary productivity (NPP), transpiration, and leaf area index (LAI) in ambient CO2 treatments. Model outputs were compared against observations using a range of goodness-of-fit statistics. Many models simulated annual NPP and transpiration within observed uncertainty. We demonstrate, however, that high goodness-of-fit values do not necessarily indicate a successful model, because simulation accuracy may be achieved through compensating biases in component variables. For example, transpiration accuracy was sometimes achieved with compensating biases in leaf area index and transpiration per unit leaf area. Our approach to model-data synthesis therefore goes beyond goodness-of-fit to investigate the success of alternative representations of component processes. Here we demonstrate this approach by comparing competing model hypotheses determining peak LAI. Of three alternative hypotheses—(1) optimization to maximize carbon export, (2) increasing specific leaf area with canopy depth, and (3) the pipe model—the pipe model produced peak LAI closest to the observations. This example illustrates how data sets from intensive field experiments such as FACE can be used to reduce model uncertainty despite compensating biases by evaluating individual model assumptions

Measurement of the cross-section and charge asymmetry of WW bosons produced in proton-proton collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

This paper presents measurements of the $W^+ \rightarrow \mu^+\nu$ and $W^- \rightarrow \mu^-\nu$ cross-sections and the associated charge asymmetry as a function of the absolute pseudorapidity of the decay muon. The data were collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS experiment at the LHC and correspond to a total integrated luminosity of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the 1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured with an uncertainty between 0.002 and 0.003. The results are compared with predictions based on next-to-next-to-leading-order calculations with various parton distribution functions and have the sensitivity to discriminate between them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables, submitted to EPJC. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13

Search for chargino-neutralino production with mass splittings near the electroweak scale in three-lepton final states in √s=13 TeV pp collisions with the ATLAS detector

A search for supersymmetry through the pair production of electroweakinos with mass splittings near the electroweak scale and decaying via on-shell W and Z bosons is presented for a three-lepton final state. The analyzed proton-proton collision data taken at a center-of-mass energy of √s=13  TeV were collected between 2015 and 2018 by the ATLAS experiment at the Large Hadron Collider, corresponding to an integrated luminosity of 139  fb−1. A search, emulating the recursive jigsaw reconstruction technique with easily reproducible laboratory-frame variables, is performed. The two excesses observed in the 2015–2016 data recursive jigsaw analysis in the low-mass three-lepton phase space are reproduced. Results with the full data set are in agreement with the Standard Model expectations. They are interpreted to set exclusion limits at the 95% confidence level on simplified models of chargino-neutralino pair production for masses up to 345 GeV