T-cell derived acetylcholine aids host defenses during enteric bacterial infection with Citrobacter rodentium.

The regulation of mucosal immune function is critical to host protection from enteric pathogens but is incompletely understood. The nervous system and the neurotransmitter acetylcholine play an integral part in host defense against enteric bacterial pathogens. Here we report that acetylcholine producing-T-cells, as a non-neuronal source of ACh, were recruited to the colon during infection with the mouse pathogen Citrobacter rodentium. These ChAT+ T-cells did not exclusively belong to one Th subset and were able to produce IFNγ, IL-17A and IL-22. To interrogate the possible protective effect of acetylcholine released from these cells during enteric infection, T-cells were rendered deficient in their ability to produce acetylcholine through a conditional gene knockout approach. Significantly increased C. rodentium burden was observed in the colon from conditional KO (cKO) compared to WT mice at 10 days post-infection. This increased bacterial burden in cKO mice was associated with increased expression of the cytokines IL-1β, IL-6, and TNFα, but without significant changes in T-cell and ILC associated IL-17A, IL-22, and IFNγ, or epithelial expression of antimicrobial peptides, compared to WT mice. Despite the increased expression of pro-inflammatory cytokines during C. rodentium infection, inducible nitric oxide synthase (Nos2) expression was significantly reduced in intestinal epithelial cells of ChAT T-cell cKO mice 10 days post-infection. Additionally, a cholinergic agonist enhanced IFNγ-induced Nos2 expression in intestinal epithelial cell in vitro. These findings demonstrated that acetylcholine, produced by specialized T-cells that are recruited during C. rodentium infection, are a key mediator in host-microbe interactions and mucosal defenses

SUSTAINABLE CONSUMPTION IN TOURISM: AN APPROACH TO ITS STATE OF KNOWLEDGE

Artículo de revisiónLas investigaciones sobre prácticas ambientales han recibido una atención creciente en el área de turismo. Sin embargo, hace falta una revisión bibliográfica que explore las prácticas de consumo sustentable en el sector. Con ese fin, a partir del uso del software ATLAS.ti 9, se realizó un análisis temático de 128 artículos cuyo objetivo principal es examinar los propósitos del consumo sustentable –buenas prácticas; hábitos del consumidor; políticas públicas, y regulaciones ambientales–, sus ámbitos de aplicación –por tipo de empresa– y su relación con la innovación (por ejemplo, con el uso de ecotecnologías). En los resultados, el análisis indica que las buenas prácticas tienen una asociación positiva con la innovación (0.72), lo que demuestra que la relación está bien establecid

MOVILIDAD DE METALES EN JALES PROCEDENTES DEL DISTRITO MINERO DE GUANAJUATO, MÉXICO

Characterization of different tailings from the mining district of Guanajuato, México were carried out, including a tailing from an abandoned dam 20 years ago, a dam in operation and another coming from the mixture of different companies. The three tailings presented alkaline conditions, normal salinity, aerobic environment with oxidative tendency, low humidity, very low capacity of cationic exchange, and absence of organic matter. These conditions restrict the metal mobility. The mineralogical analysis showed that the tailings contained mainly quartz, calcite and magnetite. Tailings coming from the mixture of different companies had greater total concentrations (mg/kg) of Mn (1042.8), Al (12919.8), Fe (23911.3), Cr (71.3), Pb (24.6) and Cu (19.8). The highest concentration of Zn was observed at the abandoned tailing (53.3 mg/kg). No significant concentrations of Cd and Hg were observed, although Pb (24.6 mg/kg) and Cr (71.4 mg/kg) were detected. Leaching tests indicated that metals cannot be leached in percentages higher than 0.1%, and so these tailings do not represent an environmental risk. The low leaching of metals in the studied tailings was consistent with the mineralogical and physicochemical prevailing conditions, the low acid drainage generation potential and the high degree of stability observed in the tests of metals fractionation.Se realizó la caracterización de tres jales del distrito minero de Guanajuato: uno abandonado hace 20 años (Presa Abandonada), uno reciente (Presa en Operación) y un jal proveniente de la mezcla de diferentes compañías (Presa Mezcla). Los tres jales presentaron carácter alcalino, condiciones aerobias con tendencias oxidantes, bajo contenido de humedad, muy baja capacidad de intercambio catiónico y ausencia de materia orgánica. Estas condiciones limitan la lixiviación de metales. Los análisis mineralógicos mostraron que los jales están constituidos mayoritariamente por cuarzo, calcita y magnetita. Los jales provenientes de la Presa Mezcla presentaron las mayores concentraciones totales (mg/kg) de Mn (1042.8), Al (12919.8), Fe (23911.3), Cr (71.3), Pb (24.6) y Cu (19.8). El Zn se encontró en mayor concentración en los jales de la Presa Abandonada (53.3 mg/kg). No se observaron concentraciones significativas de Cd y Hg, pero se detectó Pb (24.6 mg/kg) y Cr (71.4 mg/kg). Las pruebas de lixiviación indicaron que ninguno de los metales lixivió en porcentajes mayores al 0.1 %. En consecuencia, los jales estudiados no representan un riesgo ambiental. La escasa lixiviación de metales fue consistente con las condiciones fisicoquímicas imperantes, la naturaleza mineralógica de los residuos, el bajo potencial de generación de drenaje ácido y el alto grado de estabilidad observado en los estudios de fraccionamiento de metales

Ultrasensitive detection and tracking of circulating tumor DNA to predict relapse and survival in patients with locally advanced cervical cancer: phase III CALLA trial analyses

BACKGROUND: After chemoradiotherapy (CRT), 30%-50% of patients with locally advanced cervical cancer (LACC) relapse, highlighting the unmet need for prognostic biomarkers. In the global randomized CALLA trial (NCT03830866), the addition of durvalumab during and after CRT did not significantly improve progression-free survival (PFS) in a biomarker-unselected intent-to-treat population. We analyzed the association of ultrasensitive circulating tumor DNA (ctDNA) and circulating human papillomavirus (cHPV) DNA detection with relapse and survival in the largest dataset in LACC to date.; PATIENTS AND METHODS: In CALLA, adult women with stage IB2-IIB node-positive or IIIA-IVA any node-status LACC were randomized 1 : 1 to receive durvalumab + CRT or CRT alone. The NeXT Personal (Personalis) ultrasensitive tumor-informed assay with up to 1800 patient-specific variants was used for ctDNA and cHPV DNA analysis at baseline, cycle 3 day 1 (C3D1, post-CRT), and C6D1 (3 months post-CRT). Correlations were analyzed between ctDNA/cHPV DNA detection and outcomes [PFS, overall survival (OS)].; RESULTS: ctDNA was detected in 98.9% (183/185) of baseline samples, with no difference between treatment arms. Detection levels of ctDNA were predictive of disease progression and survival at baseline: hazard ratios (95% confidence intervals) comparing PFS and OS, respectively, in the ctDNA less than median versus ctDNA greater than median subgroups were 0.61 (0.28-1.35) and 0.55 (0.23-1.35) with durvalumab + CRT, and 0.49 (0.26-0.95) and 0.65 (0.33-1.28) with CRT. Post-treatment trends were similar and independent of stage or lymph node status. ctDNA detection at C3D1 occurred a median of 164 days (95% confidence interval 85-250) days before clinical progression. Baseline cHPV DNA levels were similar but were only predictive following treatment.; CONCLUSIONS: This study demonstrates the potential utility of ultrasensitive detection of ctDNA as a predictive and prognostic marker of disease progression and OS in LACC independent of disease stage. Copyright © 2025 The Author(s). Published by Elsevier Ltd.. All rights reserved

Search for the lepton-flavor violating decay Bs0 →φμ±τ

A search for the lepton-flavor violating decays Bs0→φμ±τ is presented, using a sample of proton-proton collisions at center-of-mass energies of 7, 8, and 13 TeV, collected with the LHCb detector and corresponding to a total integrated luminosity of 9 fb-1. The τ leptons are selected using decays with three charged pions. No significant excess is observed, and an upper limit on the branching fraction is determined to be B(Bs0→φμ±τ)<1.0×10-5 at 90% confidence level

Measurement of D0−D‾0D^0-\overline{D}^0 mixing and search for CPCP violation with D0→K+π−D^0\rightarrow K^+\pi^- decays

A measurement of the time-dependent ratio of the $D^0\rightarrow K^+\pi^-$ to $\overline{D}^0\rightarrow K^+\pi^-$ decay rates is reported. The analysis uses a sample of proton-proton collisions corresponding to an integrated luminosity of 6 fb$^-1$ recorded by the LHCb experiment from 2015 through 2018 at a center-of-mass energy of 13 TeV. The $D^0$ meson is required to originate from a $D^{*+}\rightarrow D^0\pi^+$ decay, such that its flavor at production is inferred from the charge of the accompanying pion. The measurement is performed simultaneously for the $K^+\pi^-$ and $K^-\pi^+$ final states, allowing both mixing and $CP$-violation parameters to be determined. The value of the ratio of the decay rates at production is determined to be $R_{K\pi} = (343.1 \pm 2.0) \times 10^{-5}$. The mixing parameters are measured to be $c_{K\pi} = (51.4 \pm 3.5) \times 10^{-4}$ and $c_{K\pi}^{\prime} = (13 \pm 4) \times 10^{-6}$, where $\sqrt{R_{K\pi}}c_{K\pi}$ is the linear coefficient of the expansion of the ratio as a function of decay time in units of the $D^0$ lifetime, and $c_{K\pi}^{\prime}$ is the quadratic coefficient, both averaged between the $K^+\pi^-$ and $K^-\pi^+$ final states. The precision is improved relative to the previous best measurement by approximately 60%. No evidence for $CP$ violation is found.Comment: All figures and tables, along with machine-readable versions and any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/Publications/LHCbProjectPublic/LHCb-PAPER-2024-008.htm

Momentum scale calibration of the LHCb spectrometer

For accurate determination of particle masses accurate knowledge of the momentum scale of the detectors is crucial. The procedure used to calibrate the momentum scale of the LHCb spectrometer is described and illustrated using the performance obtained with an integrated luminosity of 1.6 fb^−1 collected during 2016 in pp running. The procedure uses large samples of J/ψ → μ+ μ- and B+ → J/ψ K+ decays and leads to a relative accuracy of 3 × 10^−4 on the momentum scale

Search for the rare decay of charmed baryon Λc+ into the pμ+μ- final state

A search for the nonresonant Λc+→pμ+μ- decay is performed using proton-proton collision data recorded at a center-of-mass energy of 13 TeV by the LHCb experiment, corresponding to an integrated luminosity of 5.4 fb-1. No evidence for the decay is found in the dimuon invariant-mass regions where the expected contributions of resonances is subdominant. The upper limit on the branching fraction of the Λc+→pμ+μ- decay is determined to be 2.9(3.2)×10-8 at 90%(95%) confidence level. The branching fractions in the dimuon invariant-mass regions dominated by the η, ρ and ω resonances are also determined