Cellular Mechanisms Underlying the Laxative Effect of Flavonol Naringenin on Rat Constipation Model

BACKGROUND & AIMS: Symptoms of constipation are extremely common, especially in the elderly. The present study aim to identify an efficacious treatment strategy for constipation by evaluating the secretion-promoting and laxative effect of a herbal compound, naringenin, on intestinal epithelial anion secretion and a rat constipation model, respectively. METHODS/PRINCIPAL FINDINGS: In isolated rat colonic crypts, mucosal addition of naringenin (100 microM) elicited a concentration-dependent and sustained increase in the short-circuit current (I(SC)), which could be inhibited in Cl- free solution or by bumetanide and DPC (diphenylamine-2-carboxylic acid), but not by DIDS (4, 4'- diisothiocyanatostilbene-2, 2'-disulfonic acid). Naringenin could increase intracellular cAMP content and PKA activity, consisted with that MDL-12330A (N-(Cis-2-phenyl-cyclopentyl) azacyclotridecan-2-imine-hydrochloride) pretreatment reduced the naringenin-induced I(SC). In addition, significant inhibition of the naringenin-induced I(SC) by quinidine indicated that basolateral K+ channels were involved in maintaining this cAMP-dependent Cl- secretion. Naringenin-evoked whole cell current which exhibited a linear I-V relationship and time-and voltage- independent characteristics was inhibited by DPC, indicating that the cAMP activated Cl- conductance most likely CFTR (cystic fibrosis transmembrane conductance regulator) was involved. In rat constipation model, administration of naringenin restored the level of fecal output, water content and mucus secretion compared to loperamide-administrated group. CONCLUSIONS: Taken together, our data suggest that naringenin could stimulate Cl- secretion in colonic epithelium via a signaling pathway involving cAMP and PKA, hence provide an osmotic force for subsequent colonic fluid secretion by which the laxative effect observed in the rat constipation model. Naringenin appears to be a novel alternative treatment strategy for constipation

Luminosity determination using Z boson production at the CMS experiment

Data Availability Statement - This manuscript has no associated data or the data will not be deposited. [Authors’ comment: Release and preser vation of data used by the CMS Collaboration as the basis for publi cations is guidedbytheCMSpolicyasstatedinhttps://cms-docdb.cern. ch/cgibin/PublicDocDB/RetrieveFile?docid=6032&filename=CMSD ataPolicyV1.2.pdf&version=2. CMS data preservation,re-use and open access policy.]The measurement of Z boson production is presented as a method to determine the integrated luminosity of CMS data sets. The analysis uses proton–proton collision data, recorded by the CMS experiment at the CERN LHC in 2017 at a center-of-mass energy of 13 TeV . Events with Z bosons decaying into a pair of muons are selected. The total number of Z bosons produced in a fiducial volume is determined, together with the identification efficiencies and correlations from the same data set, in small intervals of 20 pb-1 of integrated luminosity, thus facilitating the efficiency and rate measurement as a function of time and instantaneous luminosity. Using the ratio of the efficiency-corrected numbers of Z bosons, the precisely measured integrated luminosity of one data set is used to determine the luminosity of another. For the first time, a full quantitative uncertainty analysis of the use of Z bosons for the integrated luminosity measurement is performed. The uncertainty in the extrapolation between two data sets, recorded in 2017 at low and high instantaneous luminosity, is less than 0.5%. We show that the Z boson rate measurement constitutes a precise method, complementary to traditional methods, with the potential to improve the measurement of the integrated luminosity.SCOAP

Search for top squarks in the four-body decay mode with single lepton final states in proton-proton collisions at √s = 13 TeV

A preprint version of the article is available at arXiv:2301.08096v2 [hep-ex], https://arxiv.org/abs/2301.08096 . Comments: Replaced with the published version. Added the journal reference and the DOI. All the figures and tables can be found at https://cms-results.web.cern.ch/cms-results/public-results/publications/SUS-21-003 (CMS Public Pages).A search for the pair production of the lightest supersymmetric partner of the top quark, the top squark (t ~1), is presented. The search targets the four-body decay of the t ~1 , which is preferred when the mass difference between the top squark and the lightest supersymmetric particle is smaller than the mass of the W boson. This decay mode consists of a bottom quark, two other fermions, and the lightest neutralino (χ~10), which is assumed to be the lightest supersymmetric particle. The data correspond to an integrated luminosity of 138 fb−1 of proton-proton collisions at a center-of-mass energy of 13 TeV collected by the CMS experiment at the CERN LHC. Events are selected using the presence of a high-momentum jet, an electron or muon with low transverse momentum, and a significant missing transverse momentum. The signal is selected based on a multivariate approach that is optimized for the difference between m(t ~1) and m(χ~10). The contribution from leading background processes is estimated from data. No significant excess is observed above the expectation from standard model processes. The results of this search exclude top squarks at 95% confidence level for masses up to 480 and 700 GeV for m(t ~1) − m(χ~10) = 10 and 80 GeV, respectively. [Figure not available: see fulltext.].SCOAP3

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Measurement of the production cross section for a W boson in association with a charm quark in proton–proton collisions at √s=13TeV

Data Availability: This manuscript has no associated data or the data will not be deposited. [Authors’ comment: Release and preservation of data used by the CMS Collaboration as the basis for publications is guided by the CMS policy as stated in https://cms-docdb.cern.ch/cgi-bin/PublicDocDB/RetrieveFile?docid=6032 &filename=CMSDataPolicyV1.2.pdf &version=2. CMS data preservation, re-use and open access policy].A preprint version of the article is available at arXiv: https://arxiv.org/abs/2308.02285 .The strange quark content of the proton is probed through the measurement of the production cross section for a W boson and a charm (c) quark in proton–proton collisions at a center-of-mass energy of 13 TeV . The analysis uses a data sample corresponding to a total integrated luminosity of 138 fb-1 collected with the CMS detector at the LHC. The W bosons are identified through their leptonic decays to an electron or a muon, and a neutrino. Charm jets are tagged using the presence of a muon or a secondary vertex inside the jet. The W + c production cross section and the cross section ratio Rc±=σ(W++c¯)/σ(W-+c) are measured inclusively and differentially as functions of the transverse momentum and the pseudorapidity of the lepton originating from the W boson decay. The precision of the measurements is improved with respect to previous studies, reaching 1% in Rc±=0.950±0.005(stat)±0.010(syst) . The measurements are compared with theoretical predictions up to next-to-next-to-leading order in perturbative quantum chromodynamics.SCOAP

Measurement of the top quark mass using a profile likelihood approach with the lepton + jets final states in proton–proton collisions at √s = 13 TeV

Data Availability Statement This manuscript has no associated data or the data will not be deposited. [Authors’ comment: Release and preservation of data used by the CMS Collaboration as the basis for publications is guided by the CMS policy as stated in “https://cms-docdb.cern.ch/cgi-bin/PublicDocDB/RetrieveFile?docid=6032 &filename=CMSDataPolicyV1.2.pdf &version=2 CMS data preservation, re-use and open access policy”].A preprint version of the article is available at arXiv, arXiv:2302.01967 [hep-ex]. It was replaced with the published version. All the figures and tables can be found at: https://cms-results.web.cern.ch/cms-results/public-results/publications/TOP-20-008 (CMS Public Pages).Report number: CMS-TOP-20-008, CERN-EP-2022-245.Copyright © CERN for the benefit of the CMS collaboration 2023. The mass of the top quark is measured in 36.3 fb-1 of LHC proton–proton collision data collected with the CMS detector at √s = 13 TeV . The measurement uses a sample of top quark pair candidate events containing one isolated electron or muon and at least four jets in the final state. For each event, the mass is reconstructed from a kinematic fit of the decay products to a top quark pair hypothesis. A profile likelihood method is applied using up to four observables per event to extract the top quark mass. The top quark mass is measured to be 171.77 ± 0.37 GeV. This approach significantly improves the precision over previous measurements.SCOAP3

First measurement of the top quark pair production cross section in proton-proton collisions at s\sqrt{s} = 13.6 TeV

A preprint version of the article is available at arXiv:2303.10680v3 [hep-ex], https://arxiv.org/abs/2303.10680v3 . Comments: Replaced with the published version. Added the journal reference and the DOI. All the figures and tables, including an additional supplementary figure, can be found at https://cms-results.web.cern.ch/cms-results/public-results/publications/TOP-22-012 (CMS Public Pages). Report number: CMS-TOP-22-012, CERN-EP-2023-021.The first measurement of the top quark pair (tt¯) production cross section in proton-proton collisions at √s = 13.6 TeV is presented. Data recorded with the CMS detector at the CERN LHC in Summer 2022, corresponding to an integrated luminosity of 1.21 fb^−1, are analyzed. Events are selected with one or two charged leptons (electrons or muons) and additional jets. A maximum likelihood fit is performed in event categories defined by the number and flavors of the leptons, the number of jets, and the number of jets identified as originating from b quarks. An inclusive tt¯ production cross section of 881 ± 23 (stat+syst) ± 20 (lumi) pb is measured, in agreement with the standard model prediction of 924 +32−40 pb.SCOAP3

Search for a high-mass dimuon resonance produced in association with b quark jets at s\sqrt{s} = 13 TeV

A preprint version of the article is available at arXiv:2307.08708v2 [hep-ex], https://arxiv.org/abs/2307.08708v2 . Comments: Replaced with the published version. Added the journal reference and the DOI. All the figures and tables can be found at https://cms-results.web.cern.ch/cms-results/public-results/publications/EXO-22-016 (CMS Public Pages). Report number: CMS-EXO-22-016, CERN-EP-2023-122.A search for high-mass dimuon resonance production in association with one or more b quark jets is presented. The study uses proton-proton collision data collected with the CMS detector at the LHC corresponding to an integrated luminosity of 138 fb^−1 at a center-of-mass energy of 13 TeV. Model-independent limits are derived on the number of signal events with exactly one or more than one b quark jet. Results are also interpreted in a lepton-flavor-universal model with Z′ boson couplings to a bb quark pair (gb), an sb quark pair (gbδbs), and any same-flavor charged lepton (gℓ) or neutrino pair (gν), with |gν|=|gℓ|. For a Z′ boson with a mass mZ′ = 350 GeV (2 TeV) and |δbs| < 0.25, the majority of the parameter space with 0.0057 < |gℓ| < 0.35 (0.25 < |gℓ| < 0.43) and 0.0079 < |gb| < 0.46 (0.34 < |gb| < 0.57) is excluded at 95% confidence level. Finally, constraints are set on a Z′ model with parameters consistent with low-energy b → sℓℓ measurements. In this scenario, most of the allowed parameter space is excluded for a Z′ boson with 350 <mZ′ < 500 GeV, while the constraints are less stringent for higher mZ′ hypotheses. This is the first dedicated search at the LHC for a high-mass dimuon resonance produced in association with multiple b quark jets, and the constraints obtained on models with this signature are the most stringent to date.SCOAP3

Measurements of the azimuthal anisotropy of prompt and nonprompt charmonia in PbPb collisions at √sNN = 5.02 TeV

A preprint version of the article is available at arXiv:2305.16928v2 [hep-ex], https://arxiv.org/abs/2305.16928. It has not been certified by peer review.The second-order (v 2) and third-order (v 3) Fourier coefficients describing the azimuthal anisotropy of prompt and nonprompt (from b-hadron decays) J/ψ, as well as prompt ψ(2S) mesons are measured in lead-lead collisions at a center-of-mass energy per nucleon pair of √sNN = 5.02 TeV. The analysis uses a data set corresponding to an integrated luminosity of 1.61 nb −1 recorded with the CMS detector. The J/ψ and ψ(2S) mesons are reconstructed using their dimuon decay channel. The v 2 and v 3 coefficients are extracted using the scalar product method and studied as functions of meson transverse momentum and collision centrality. The measured v 2 values for prompt J/ψ mesons are found to be larger than those for nonprompt J/ψ mesons. The prompt J/ψ v 2 values at high p T are found to be underpredicted by a model incorporating only parton energy loss effects in a quark-gluon plasma medium. Prompt and nonprompt J/ψ meson v 3 and prompt ψ(2S) v 2 and v 3 values are also reported for the first time, providing new information about heavy quark interactions in the hot and dense medium created in heavy ion collisions. [Figure not available: see fulltext.]SCOAP3

Measurement of the τ lepton polarization in Z boson decays in proton-proton collisions at √s = 13 TeV

A preprint version of the article is available at arXiv:2309.12408v2 [hep-ex], https://arxiv.org/abs/2309.12408. It has not been certified by peer review.The polarization of τ leptons is measured using leptonic and hadronic τ lepton decays in Z → τ+ τ− events in proton-proton collisions at √s = 13 TeV recorded by CMS at the CERN LHC with an integrated luminosity of 36.3 fb−1. The measured τ− lepton polarization at the Z boson mass pole is Pτ(Z) = −0.144 ± 0.006 (stat) ± 0.014 (syst) = −0.144 ± 0.015, in good agreement with the measurement of the τ lepton asymmetry parameter of Aτ = 0.1439 ± 0.0043 = − Pτ(Z) at LEP. The τ lepton polarization depends on the ratio of the vector to axial-vector couplings of the τ leptons in the neutral current expression, and thus on the effective weak mixing angle sin2 θWeff , independently of the Z boson production mechanism. The obtained value sin2 θWeff = 0.2319 ± 0.0008(stat) ± 0.0018(syst) = 0.2319 ± 0.0019 is in good agreement with measurements at e+ e− colliders. [Figure not available: see fulltext.].SCOAP3