Host genotype and genetic diversity shape the evolution of a novel bacterial infection

Pathogens continue to emerge from increased contact with novel host species. Whilst these hosts can represent distinct environments for pathogens, the impacts of host genetic background on how a pathogen evolves post-emergence are unclear. In a novel interaction, we experimentally evolved a pathogen (Staphylococcus aureus) in populations of wild nematodes (Caenorhabditis elegans) to test whether host genotype and genetic diversity affect pathogen evolution. After ten rounds of selection, we found that pathogen virulence evolved to vary across host genotypes, with differences in host metal ion acquisition detected as a possible driver of increased host exploitation. Diverse host populations selected for the highest levels of pathogen virulence, but infectivity was constrained, unlike in host monocultures. We hypothesise that population heterogeneity might pool together individuals that contribute disproportionately to the spread of infection or to enhanced virulence. The genomes of evolved populations were sequenced, and it was revealed that pathogens selected in distantly-related host genotypes diverged more than those in closely-related host genotypes. S. aureus nevertheless maintained a broad host range. Our study provides unique empirical insight into the evolutionary dynamics that could occur in other novel infections of wildlife and humans

Carnitine Acetyltransferase Mitigates Metabolic Inertia and Muscle Fatigue during Exercise

SummaryAcylcarnitine metabolites have gained attention as biomarkers of nutrient stress, but their physiological relevance and metabolic purpose remain poorly understood. Short-chain carnitine conjugates, including acetylcarnitine, derive from their corresponding acyl-CoA precursors via the action of carnitine acetyltransferase (CrAT), a bidirectional mitochondrial matrix enzyme. We show here that contractile activity reverses acetylcarnitine flux in muscle, from net production and efflux at rest to net uptake and consumption during exercise. Disruption of this switch in mice with muscle-specific CrAT deficiency resulted in acetyl-CoA deficit, perturbed energy charge, and diminished exercise tolerance, whereas acetylcarnitine supplementation produced opposite outcomes in a CrAT-dependent manner. Likewise, in exercise-trained compared to untrained humans, post-exercise phosphocreatine recovery rates were positively associated with CrAT activity and coincided with dramatic shifts in muscle acetylcarnitine dynamics. These findings show acetylcarnitine serves as a critical acetyl buffer for working muscles and provide insight into potential therapeutic strategies for combatting exercise intolerance

Comparison of s- and d-wave gap symmetry in nonequilibrium superconductivity

Recent application of ultrafast pump/probe optical techniques to superconductors has renewed interest in nonequilibrium superconductivity and the predictions that would be available for novel superconductors, such as the high-Tc cuprates. We have reexamined two of the classical models which have been used in the past to interpret nonequilibrium experiments with some success: the mu* model of Owen and Scalapino and the T* model of Parker. Predictions depend on pairing symmetry. For instance, the gap suppression due to excess quasiparticle density n in the mu* model, varies as n^{3/2} in d-wave as opposed to n for s-wave. Finally, we consider these models in the context of S-I-N tunneling and optical excitation experiments. While we confirm that recent pump/probe experiments in YBCO, as presently interpreted, are in conflict with d-wave pairing, we refute the further claim that they agree with s-wave.Comment: 14 pages, 11 figure

Genetic polymorphisms of diabetes-related genes, their interaction with diabetes status, and breast cancer incidence and mortality: The Long Island Breast Cancer Study Project

To examine 143 diabetes risk single nucleotide polymorphisms (SNPs), identified from genome-wide association studies, in association with breast cancer (BC) incidence and subsequent mortality. A population-based sample of Caucasian women with first primary invasive BC (n = 817) and controls (n = 1021) were interviewed to assess diabetes status. Using the National Death Index, women with BC were followed for >18 years during which 340 deaths occurred (139 BC deaths). Genotyping was done using DNA extracted from blood samples. We used unconditional logistic regression to estimate age-adjusted odds ratios and 95% confidence intervals (CIs) for BC incidence, and Cox regression to estimate age-adjusted hazard ratios and CIs for all-cause and BC-specific mortality. Twelve SNPs were associated with BC risk in additive genotype models, at α = 0.05. The top three significant SNPs included SLC30A8-rs4876369 (P = 0.0034), HHEX-rs11187146 (P = 0.0086), and CDKN2A/CDKN2B-rs1333049 (P = 0.0094). Diabetes status modified the associations between rs4876369 and rs2241745 and BC incidence, on the multiplicative interaction scale. Six SNPs were associated with all-cause (CDKAL1-rs981042, P = 0.0032; HHEX-rs1111875, P = 0.0361; and INSR-rs919275, P = 0.0488) or BC-specific (CDKN2A/CDKN2B-rs3218020, P = 0.0225; CDKAL1-rs981042, P = 0.0246; and TCF2/HNF1B-rs3094508, P = 0.0344) mortality in additive genotype models, at α = 0.05. Genetic polymorphisms that increase the risk of developing diabetes may also increase the risk of developing and dying from BC

Efficacy of a Commercial Weight Management Program Compared with a Do-It-Yourself Approach: A Randomized Clinical Trial

Importance: Given the prevalence of obesity, accessible and effective treatment options are needed to manage obesity and its comorbid conditions. Commercial weight management programs are a potential solution to the lack of available treatment, providing greater access at lower cost than clinic-based approaches, but few commercial programs have been rigorously evaluated. Objective: To compare the differences in weight change between individuals randomly assigned to a commercial weight management program and those randomly assigned to a do-it-yourself (DIY) approach. Design, Setting, and Participants: This 1-year, randomized clinical trial conducted in the United States, Canada, and United Kingdom between June 19, 2018, and November 30, 2019, enrolled 373 adults aged 18 to 75 years with a body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) of 25 to 45. Assessors were blinded to treatment conditions. Interventions: A widely available commercial weight management program that included reduced requirements for dietary self-monitoring and recommendations for a variety of DIY approaches to weight loss. Main Outcomes and Measures: The primary outcomes were the difference in weight change between the 2 groups at 3 and 12 months. The a priori hypothesis was that the commercial program would result in greater weight loss than the DIY approach at 3 and 12 months. Analyses were performed on an intention-To-Treat basis. Results: The study include 373 participants (272 women [72.9%]; mean [SD] BMI, 33.8 [5.2]; 77 [20.6%] aged 18-34 years, 74 [19.8%] aged 35-43 years, 82 [22.0%] aged 44-52 years, and 140 [37.5%] aged 53-75 years). At 12 months, retention rates were 88.8% (166 of 187) for the commercial weight management program group and 95.7% (178 of 186) for the DIY group. At 3 months, participants in the commercial program had a mean (SD) weight loss of-3.8 (4.1) kg vs-1.8 (3.7) kg among those in the DIY group. At 12 months, participants in the commercial program had a mean (SD) weight loss of-4.4 (7.3) kg vs-1.7 (7.3) kg among those in the DIY group. The mean difference between groups was-2.0 kg (97.5% CI,-2.9 to-1.1 kg) at 3 months (P <.001) and-2.6 kg (97.5% CI,-4.3 to-0.8 kg) at 12 months (P <.001). A greater percentage of participants in the commercial program group than participants in the DIY group achieved loss of 5% of body weight at both 3 months (40.7% [72 of 177] vs 18.6% [34 of 183]) and 12 months (42.8% [71 of 166] vs 24.7% [44 of 178]). Conclusions and Relevance: Adults randomly assigned to a commercial weight management program with reduced requirements for dietary self-monitoring lost more weight and were more likely to achieve weight loss of 5% at 3 and 12 months than adults following a DIY approach. This study contributes data on the efficacy of commercial weight management programs and DIY weight management approaches. Trial Registration: ClinicalTrials.gov Identifier: NCT03571893

Longitudinal double-spin asymmetry and cross section for inclusive neutral pion production at midrapidity in polarized proton collisions at sqrt(s) = 200 GeV

We report a measurement of the longitudinal double-spin asymmetry A_LL and the differential cross section for inclusive Pi0 production at midrapidity in polarized proton collisions at sqrt(s) = 200 GeV. The cross section was measured over a transverse momentum range of 1 < p_T < 17 GeV/c and found to be in good agreement with a next-to-leading order perturbative QCD calculation. The longitudinal double-spin asymmetry was measured in the range of 3.7 < p_T < 11 GeV/c and excludes a maximal positive gluon polarization in the proton. The mean transverse momentum fraction of Pi0's in their parent jets was found to be around 0.7 for electromagnetically triggered events.Comment: 6 pages, 3 figures, submitted to Phys. Rev. D (RC

Evolution of the differential transverse momentum correlation function with centrality in Au+Au collisions at sNN=200\sqrt{s_{NN}} = 200 GeV

We present first measurements of the evolution of the differential transverse momentum correlation function, {\it C}, with collision centrality in Au+Au interactions at $\sqrt{s_{NN}} = 200$ GeV. {\it C} exhibits a strong dependence on collision centrality that is qualitatively similar to that of number correlations previously reported. We use the observed longitudinal broadening of the near-side peak of {\it C} with increasing centrality to estimate the ratio of the shear viscosity to entropy density, $\eta/s$, of the matter formed in central Au+Au interactions. We obtain an upper limit estimate of $\eta/s$ that suggests that the produced medium has a small viscosity per unit entropy.Comment: 7 pages, 4 figures, STAR paper published in Phys. Lett.

High pTp_{T} non-photonic electron production in pp+pp collisions at s\sqrt{s} = 200 GeV

We present the measurement of non-photonic electron production at high transverse momentum ($p_T >$ 2.5 GeV/$c$) in $p$ + $p$ collisions at $\sqrt{s}$ = 200 GeV using data recorded during 2005 and 2008 by the STAR experiment at the Relativistic Heavy Ion Collider (RHIC). The measured cross-sections from the two runs are consistent with each other despite a large difference in photonic background levels due to different detector configurations. We compare the measured non-photonic electron cross-sections with previously published RHIC data and pQCD calculations. Using the relative contributions of B and D mesons to non-photonic electrons, we determine the integrated cross sections of electrons ($\frac{e^++e^-}{2}$) at 3 GeV/$c < p_T <~$10 GeV/$c$ from bottom and charm meson decays to be ${d\sigma_{(B\to e)+(B\to D \to e)} \over dy_e}|_{y_e=0}$ = 4.0$\pm0.5$({\rm stat.})$\pm1.1$({\rm syst.}) nb and ${d\sigma_{D\to e} \over dy_e}|_{y_e=0}$ = 6.2$\pm0.7$({\rm stat.})$\pm1.5$({\rm syst.}) nb, respectively.Comment: 17 pages, 17 figure

Longitudinal scaling property of the charge balance function in Au + Au collisions at 200 GeV

We present measurements of the charge balance function, from the charged particles, for diverse pseudorapidity and transverse momentum ranges in Au + Au collisions at 200 GeV using the STAR detector at RHIC. We observe that the balance function is boost-invariant within the pseudorapidity coverage [-1.3, 1.3]. The balance function properly scaled by the width of the observed pseudorapidity window does not depend on the position or size of the pseudorapidity window. This scaling property also holds for particles in different transverse momentum ranges. In addition, we find that the width of the balance function decreases monotonically with increasing transverse momentum for all centrality classes.Comment: 6 pages, 3 figure