Can sexual selection drive female life histories? A comparative study on Galliform birds

Sexual selection is an important driver of many of the most spectacular morphological traits that we find in the animal kingdom (for example see Andersson, 1994). As such, sexual selection is most often emphasized as

Glucose consumption rate-dependent transcriptome profiling of Escherichia coli provides insight on performance as microbial factories

peer reviewedBACKGROUND: The modification of glucose import capacity is an engineering strategy that has been shown to improve the characteristics of Escherichia coli as a microbial factory. A reduction in glucose import capacity can have a positive effect on production strain performance, however, this is not always the case. In this study, E. coli W3110 and a group of four isogenic derivative strains, harboring single or multiple deletions of genes encoding phosphoenolpyruvate:sugar phosphotransferase system (PTS)-dependent transporters as well as non-PTS transporters were characterized by determining their transcriptomic response to reduced glucose import capacity. RESULTS: These strains were grown in bioreactors with M9 mineral salts medium containing 20 g/L of glucose, where they displayed specific growth rates ranging from 0.67 to 0.27 h-1, and specific glucose consumption rates (qs) ranging from 1.78 to 0.37 g/g h. RNA-seq analysis revealed a transcriptional response consistent with carbon source limitation among all the mutant strains, involving functions related to transport and metabolism of alternate carbon sources and characterized by a decrease in genes encoding glycolytic enzymes and an increase in gluconeogenic functions. A total of 107 and 185 genes displayed positive and negative correlations with qs, respectively. Functions displaying positive correlation included energy generation, amino acid biosynthesis, and sugar import. CONCLUSION: Changes in gene expression of E. coli strains with impaired glucose import capacity could be correlated with qs values and this allowed an inference of the physiological state of each mutant. In strains with lower qs values, a gene expression pattern is consistent with energy limitation and entry into the stationary phase. This physiological state could explain why these strains display a lower capacity to produce recombinant protein, even when they show very low rates of acetate production. The comparison of the transcriptomes of the engineered strains employed as microbial factories is an effective approach for identifying favorable phenotypes with the potential to improve the synthesis of biotechnological products. © 2022. The Author(s)

Post-ischaemic silencing of p66Shc reduces ischaemia/reperfusion brain injury and its expression correlates to clinical outcome in stroke

In light of the limited repertoire of therapeutical options available for the treatment of ischaemic stroke, the identification of novel potential targets is vital; in this respect, the present study demonstrates that the adaptor protein p66Shc holds this potential as an adjunct therapy to thrombolysis. Post-ischaemic silencing of p66Shc protein yielded beneficial effects in a mouse model of I/R brain injury underlying an interesting translational perspective for this target protein. Further, in proof-of-principle clinical experiments using PBMs, we demonstrate that p66Shc gene expression is transiently increased and that its levels correlate to short-term outcome in ischaemic stroke patients. Although these latter experiments are not directly relevant to the experiments performed in mice and in human endothelial cells, they provide novel important information about p66Shc regulation in stroke patients and set the basis for further investigations aimed at assessing the potential for p66Shc to become a novel therapeutic target as an adjunct of thrombolysis for the management of acute ischaemic strok

Coordinated effects of sequence variation on DNA binding, chromatin structure, and transcription.

DNA sequence variation has been associated with quantitative changes in molecular phenotypes such as gene expression, but its impact on chromatin states is poorly characterized. To understand the interplay between chromatin and genetic control of gene regulation, we quantified allelic variability in transcription factor binding, histone modifications, and gene expression within humans. We found abundant allelic specificity in chromatin and extensive local, short-range, and long-range allelic coordination among the studied molecular phenotypes. We observed genetic influence on most of these phenotypes, with histone modifications exhibiting strong context-dependent behavior. Our results implicate transcription factors as primary mediators of sequence-specific regulation of gene expression programs, with histone modifications frequently reflecting the primary regulatory event

Effectiveness and safety of obeticholic acid in a Southern European multicenter cohort of patients with primary biliary cholangitis and suboptimal response to ursodeoxycholic acid

Background Obeticholic acid (OCA) was recently approved as the only on-label alternative for patients with primary biliary cholangitis (PBC) with intolerance or suboptimal response to ursodeoxycholic acid (UDCA). However, few data are available outside clinical trials. Aim To assess the effectiveness and safety of OCA in a real-world cohort of patients with non-effective UDCA therapy. Methods Open-label, prospective, real-world, multicentre study, enrolling consecutive patients who did not meet Paris II criteria, from 18 institutions in Spain and Portugal. Effectiveness was assessed by the changes in GLOBE and UK-PBC scores from baseline. POISE and Paris II criteria were evaluated after 12 months of OCA . Liver fibrosis was evaluated by FIB-4 and AST to platelet ratio index (APRI). Results One hundred and twenty patients were eligible, median time since PBC diagnosis 9.3 (4.0-13.8) years, 21.7% had cirrhosis, and 26.7% received had previous or concomitant treatment with fibrates. Seventy-eight patients completed at least 1 year of OCA. The Globe-PBC score decreased to 0.17 (95% CI 0.05 to 0.28; P = 0.005) and the UK-PBC score decreased to 0.81 (95% CI -0.19 to 1.80; P = 0.11). There was a significant decrease in alkaline phosphatase of 81.3 U/L (95% CI 42.5 to 120; P < 0.001), ALT 22.1 U/L (95% CI 10.4 to 33.8; P < 0.001) and bilirubin 0.12 mg/dL (95% CI 0 to 0.24; P = 0.044). FIB-4 and APRI remained stable. According to the POISE criteria, 29.5% (23 out of 78) achieved response. The adverse events rate was 35%; 11.67% discontinued (8.3% due to pruritus). Conclusions This study supports data from phase III trials with significant improvement of PBC-Globe continuous prognostic marker score among OCA-treated patients with good tolerability

Predictors of adherence to a Mediterranean-type diet in the PREDIMED trial.

BACKGROUND: Determinants of dietary changes obtained with a nutritional intervention promoting the Mediterranean diet have been rarely evaluated. AIM: To identify predictors of higher success of an intervention aimed to increase adherence to a Mediterranean diet (MeDiet) in individuals at high cardiovascular risk participating in a trial for primary prevention of cardiovascular disease: the PREDIMED (PREvención con DIeta MEDiterránea) trial. Candidate predictors included demographic and socioeconomic characteristics, cardiovascular risk factors, and baseline dietary habits. METHODS: A total of 1,048 asymptomatic subjects aged 55-80 years allocated to the active intervention groups (subjects in the control group were excluded). Participants' characteristics were assessed at baseline among subjects. Dietary changes were evaluated after 12 months. Main outcome measures were: attained changes in five dietary goals: increases in (1) fruit consumption, (2) vegetable consumption, (3) monounsaturated fatty acid (MUFA)/saturated fatty acid (SFA) ratio, and decreases in (4) sweets and pastries consumption, (5) and meat consumption. Univariate and multivariate logistic regression analyses were used to examine associations between the candidate predictors and likelihood of attaining optimum dietary change (improved adherence to a MeDiet). RESULTS: Among men, positive changes toward better compliance with the MeDiet were more frequent among non-diabetics, and among those with worse dietary habits at baseline (higher consumption of meat, higher SFA intake, lower consumption of fruit and vegetables). Among women, marital status (married) and worse baseline dietary habits (high in meats, low in fruits and vegetables) were the strongest predictors of success in improving adherence to the MeDiet. CONCLUSIONS: Some participant characteristics (marital status and baseline dietary habits) could contribute to predicting the likelihood of achieving dietary goals in interventions aimed to improve adherence to a MeDiet, and may be useful for promoting individualized long-term dietary changes and improving the effectiveness of dietary counseling

Primary prevention of cardiovascular disease with a Mediterranean diet

BACKGROUND: Observational cohort studies and a secondary prevention trial have shown an inverse association between adherence to the Mediterranean diet and cardiovascular risk. We conducted a randomized trial of this diet pattern for the primary prevention of cardiovascular events. METHODS: In a multicenter trial in Spain, we randomly assigned participants who were at high cardiovascular risk, but with no cardiovascular disease at enrollment, to one of three diets: a Mediterranean diet supplemented with extra-virgin olive oil, a Mediterranean diet supplemented with mixed nuts, or a control diet (advice to reduce dietary fat). Participants received quarterly individual and group educational sessions and, depending on group assignment, free provision of extra-virgin olive oil, mixed nuts, or small nonfood gifts. The primary end point was the rate of major cardiovascular events (myocardial infarction, stroke, or death from cardiovascular causes). On the basis of the results of an interim analysis, the trial was stopped after a median follow-up of 4.8 years. RESULTS: A total of 7447 persons were enrolled (age range, 55 to 80 years); 57% were women. The two Mediterranean-diet groups had good adherence to the intervention, according to self-reported intake and biomarker analyses. A primary end-point event occurred in 288 participants. The multivariable-adjusted hazard ratios were 0.70 (95% confidence interval [CI], 0.54 to 0.92) and 0.72 (95% CI, 0.54 to 0.96) for the group assigned to a Mediterranean diet with extra-virgin olive oil (96 events) and the group assigned to a Mediterranean diet with nuts (83 events), respectively, versus the control group (109 events). No diet-related adverse effects were reported. CONCLUSIONS: Among persons at high cardiovascular risk, a Mediterranean diet supplemented with extra-virgin olive oil or nuts reduced the incidence of major cardiovascular events

Quality control for the first large areas of triple-GEM chambers for the CMS endcaps

The CMS Collaboration plans to equip the very forward muon system with triple-GEM detectors that can withstand the environment of the High-Luminosity LHC.This project is at the final stages of R&D and moving to production. A large area of several 100 m 2 are to be instrumented with GEM detectors which will be produced in six different sites around the world. A common construction and quality control procedure is required to ensure the performance of each detector.The quality control steps will include optical inspection,cleaning and baking of all materials and parts used to build the detector,leakage current tests of the GEM foils,high voltage tests,gas leak tests of the chambers and monitoring pressures time,gain calibration to know the optimal operation region of the detector,gain uniformity tests, and studying the efficiency,noise and tracking performance of the detectors in a cosmic stand using scintillator

Measurement of the Top Quark Pair Production Cross Section in pbar-p Collisions Using Multijet Final States

We have studied tbar-t production using multijet final states in pbar-p collisions at a center-of-mass energy of 1.8 TeV, with an integrated luminosity of 110.3 pb(-1). Each of the top quarks with these final states decays exclusively to a bottom quark and a W boson, with the W bosons decaying into quark-antiquark pairs. The analysis has been optimized using neural networks to achieve the smallest expected fractional uncertainty on the tbar-t production cross section, and yields a cross section of 7.1 +/- 2.8(stat.) +/- 1.5(syst.) pb, assuming a top quark mass of 172.1 GeV/c^(2). Combining this result with previous D0 measurements, where one or both of the W bosons decay leptonically, gives a tbar t production cross section of 5.9 +/- 1.2(stat) +/- 1.1(syst) pb.Comment: 30 pages, 32 figures; no substative change in revisio

Update on the correlation of the highest energy cosmic rays with nearby extragalactic matter

Data collected by the Pierre Auger Observatory through 31 August 2007 showed evidence for anisotropy in the arrival directions of cosmic rays above the Greisen-Zatsepin-Kuz'min energy threshold, \nobreak{$6\times 10^{19}$eV}. The anisotropy was measured by the fraction of arrival directions that are less than $3.1^\circ$ from the position of an active galactic nucleus within 75 Mpc (using the V\'eron-Cetty and V\'eron $12^{\rm th}$ catalog). An updated measurement of this fraction is reported here using the arrival directions of cosmic rays recorded above the same energy threshold through 31 December 2009. The number of arrival directions has increased from 27 to 69, allowing a more precise measurement. The correlating fraction is $(38^{+7}_{-6})$, compared with $21$ expected for isotropic cosmic rays. This is down from the early estimate of $(69^{+11}_{-13})$. The enlarged set of arrival directions is examined also in relation to other populations of nearby extragalactic objects: galaxies in the 2 Microns All Sky Survey and active galactic nuclei detected in hard X-rays by the Swift Burst Alert Telescope. A celestial region around the position of the radiogalaxy Cen A has the largest excess of arrival directions relative to isotropic expectations. The 2-point autocorrelation function is shown for the enlarged set of arrival directions and compared to the isotropic expectation.Comment: Accepted for publication in Astroparticle Physics on 31 August 201