Transcriptional and post-transcriptional suppression of P450IIC11 and P450IIC12 by inflammation

AbstractInduction of inflammation in rats by treatment with endotoxin or turpentine is known to suppress levels of hepatic mRNAs for P450IIC11 and P450IIC12. We report that transcription of CYP2C12 in female rats is not significantly reduced from control levels; suppression of this gene during inflammation appears to be mediated post-transcriptionally. In contrast, transcription of CYP2C11 in male rats is reduced to 23% and to 5% of control levels by turpentine and by endotoxin, respectively. Sex-specificity of CYP2C11 expression is also regulated transcriptionally, whereas sex-specificity of CYP2C12 expression appears to be regulated by a post-transcriptional mechanism

Neuromuscular responses to mild-muscle damaging eccentric exercise in a low glycogen state.

The aim of this study was to examine the effect of low muscle glycogen on the neuromuscular responses to maximal eccentric contractions. Fourteen healthy men (22±3years) performed single-leg cycling (20min at ∼75% maximal oxygen uptake (V̇O2 max); eight 90 s sprints at a 1:1 work-to-rest ratio (5% decrements from 90% to 55% V̇O2 max until exhaustion) the evening before 100 eccentric (1.57rads(-1)) with reduced (RED) and normal glycogen (NORM). Neuromuscular responses were measured during and up to 48h after with maximal voluntary and involuntary (twitch, 20Hz and 50Hz) isometric contractions. During eccentric contractions, peak torque decreased (RED: -16.1±2.5%; NORM: -6.2±5.1%) and EMG frequency increased according to muscle length. EMG activity decreased for RED only. After eccentric contractions, maximal isometric force was reduced up to 24h for NORM (-13.5±5.8%) and 48h for RED (-7.4±10.9%). Twelve hours after eccentric contractions, twitch force and the 20:50Hz ratio were decreased for RED but not for NORM. Immediate involuntary with prolonged voluntary force loss suggests that reduced glycogen is associated with increased susceptibility to mild muscle-damaging eccentric exercise with contributions of peripheral and central mechanisms to be different during recovery

Billiards in a general domain with random reflections

We study stochastic billiards on general tables: a particle moves according to its constant velocity inside some domain ${\mathcal D} \subset {\mathbb R}^d$ until it hits the boundary and bounces randomly inside according to some reflection law. We assume that the boundary of the domain is locally Lipschitz and almost everywhere continuously differentiable. The angle of the outgoing velocity with the inner normal vector has a specified, absolutely continuous density. We construct the discrete time and the continuous time processes recording the sequence of hitting points on the boundary and the pair location/velocity. We mainly focus on the case of bounded domains. Then, we prove exponential ergodicity of these two Markov processes, we study their invariant distribution and their normal (Gaussian) fluctuations. Of particular interest is the case of the cosine reflection law: the stationary distributions for the two processes are uniform in this case, the discrete time chain is reversible though the continuous time process is quasi-reversible. Also in this case, we give a natural construction of a chord "picked at random" in ${\mathcal D}$, and we study the angle of intersection of the process with a $(d-1)$-dimensional manifold contained in ${\mathcal D}$.Comment: 50 pages, 10 figures; To appear in: Archive for Rational Mechanics and Analysis; corrected Theorem 2.8 (induced chords in nonconvex subdomains

Namibian Sign Language to English and Oshiwambo

A group of six deaf black Namibians worked with Gallaudet University linguists, Ruth Morgan and Scott Liddell, to make this dictionary.https://digitalcommons.wou.edu/oerbooks_namibiansign/1000/thumbnail.jp

Heavy quarkonium: progress, puzzles, and opportunities

A golden age for heavy quarkonium physics dawned a decade ago, initiated by the confluence of exciting advances in quantum chromodynamics (QCD) and an explosion of related experimental activity. The early years of this period were chronicled in the Quarkonium Working Group (QWG) CERN Yellow Report (YR) in 2004, which presented a comprehensive review of the status of the field at that time and provided specific recommendations for further progress. However, the broad spectrum of subsequent breakthroughs, surprises, and continuing puzzles could only be partially anticipated. Since the release of the YR, the BESII program concluded only to give birth to BESIII; the $B$-factories and CLEO-c flourished; quarkonium production and polarization measurements at HERA and the Tevatron matured; and heavy-ion collisions at RHIC have opened a window on the deconfinement regime. All these experiments leave legacies of quality, precision, and unsolved mysteries for quarkonium physics, and therefore beg for continuing investigations. The plethora of newly-found quarkonium-like states unleashed a flood of theoretical investigations into new forms of matter such as quark-gluon hybrids, mesonic molecules, and tetraquarks. Measurements of the spectroscopy, decays, production, and in-medium behavior of c\bar{c}, b\bar{b}, and b\bar{c} bound states have been shown to validate some theoretical approaches to QCD and highlight lack of quantitative success for others. The intriguing details of quarkonium suppression in heavy-ion collisions that have emerged from RHIC have elevated the importance of separating hot- and cold-nuclear-matter effects in quark-gluon plasma studies. This review systematically addresses all these matters and concludes by prioritizing directions for ongoing and future efforts.Comment: 182 pages, 112 figures. Editors: N. Brambilla, S. Eidelman, B. K. Heltsley, R. Vogt. Section Coordinators: G. T. Bodwin, E. Eichten, A. D. Frawley, A. B. Meyer, R. E. Mitchell, V. Papadimitriou, P. Petreczky, A. A. Petrov, P. Robbe, A. Vair

CSF1R inhibitor JNJ-40346527 attenuates microglial proliferation and neurodegeneration in P301S mice

Neuroinflammation and microglial activation are significant processes in Alzheimer's disease pathology. Recent genome-wide association studies have highlighted multiple immune-related genes in association with Alzheimer's disease, and experimental data have demonstrated microglial proliferation as a significant component of the neuropathology. In this study, we tested the efficacy of the selective CSF1R inhibitor JNJ-40346527 (JNJ-527) in the P301S mouse tauopathy model. We first demonstrated the anti-proliferative effects of JNJ-527 on microglia in the ME7 prion model, and its impact on the inflammatory profile, and provided potential CNS biomarkers for clinical investigation with the compound, including pharmacokinetic/pharmacodynamics and efficacy assessment by TSPO autoradiography and CSF proteomics. Then, we showed for the first time that blockade of microglial proliferation and modification of microglial phenotype leads to an attenuation of tau-induced neurodegeneration and results in functional improvement in P301S mice. Overall, this work strongly supports the potential for inhibition of CSF1R as a target for the treatment of Alzheimer's disease and other tau-mediated neurodegenerative diseases

Inflammatory biomarkers in Alzheimer's disease plasma

Introduction: Plasma biomarkers for Alzheimer's disease (AD) diagnosis/stratification are a \u201cHoly Grail\u201d of AD research and intensively sought; however, there are no well-established plasma markers. Methods: A hypothesis-led plasma biomarker search was conducted in the context of international multicenter studies. The discovery phase measured 53 inflammatory proteins in elderly control (CTL; 259), mild cognitive impairment (MCI; 199), and AD (262) subjects from AddNeuroMed. Results: Ten analytes showed significant intergroup differences. Logistic regression identified five (FB, FH, sCR1, MCP-1, eotaxin-1) that, age/APO\u3b54 adjusted, optimally differentiated AD and CTL (AUC: 0.79), and three (sCR1, MCP-1, eotaxin-1) that optimally differentiated AD and MCI (AUC: 0.74). These models replicated in an independent cohort (EMIF; AUC 0.81 and 0.67). Two analytes (FB, FH) plus age predicted MCI progression to AD (AUC: 0.71). Discussion: Plasma markers of inflammation and complement dysregulation support diagnosis and outcome prediction in AD and MCI. Further replication is needed before clinical translation

Coronavirus disease 2019 (COVID-19) research agenda for healthcare epidemiology

This SHEA white paper identifies knowledge gaps and challenges in healthcare epidemiology research related to coronavirus disease 2019 (COVID-19) with a focus on core principles of healthcare epidemiology. These gaps, revealed during the worst phases of the COVID-19 pandemic, are described in 10 sections: epidemiology, outbreak investigation, surveillance, isolation precaution practices, personal protective equipment (PPE), environmental contamination and disinfection, drug and supply shortages, antimicrobial stewardship, healthcare personnel (HCP) occupational safety, and return to work policies. Each section highlights three critical healthcare epidemiology research questions with detailed description provided in supplementary materials. This research agenda calls for translational studies from laboratory-based basic science research to well-designed, large-scale studies and health outcomes research. Research gaps and challenges related to nursing homes and social disparities are included. Collaborations across various disciplines, expertise and across diverse geographic locations will be critical

Leaf nutrients, not specific leaf area, are consistent indicators of elevated nutrient inputs

Leaf traits are frequently measured in ecology to provide a ‘common currency’ for predicting how anthropogenic pressures impact ecosystem function. Here, we test whether leaf traits consistently respond to experimental treatments across 27 globally distributed grassland sites across 4 continents. We find that specific leaf area (leaf area per unit mass)—a commonly measured morphological trait inferring shifts between plant growth strategies—did not respond to up to four years of soil nutrient additions. Leaf nitrogen, phosphorus and potassium concentrations increased in response to the addition of each respective soil nutrient. We found few significant changes in leaf traits when vertebrate herbivores were excluded in the short-term. Leaf nitrogen and potassium concentrations were positively correlated with species turnover, suggesting that interspecific trait variation was a significant predictor of leaf nitrogen and potassium, but not of leaf phosphorus concentration. Climatic conditions and pretreatment soil nutrient levels also accounted for significant amounts of variation in the leaf traits measured. Overall, we find that leaf morphological traits, such as specific leaf area, are not appropriate indicators of plant response to anthropogenic perturbations in grasslands