The RNA-binding protein HuR contributes to neuroinflammation by promoting C-C chemokine receptor 6 (CCR6) expression on Th17 cells.

In both multiple sclerosis and experimental autoimmune encephalomyelitis (EAE), the C-C chemokine receptor 6 (CCR6) is critical for pathogenic T helper 17 (Th17) cell migration to the central nervous system (CNS). Whereas many cytokines and their receptors are potently regulated via post-transcriptional mechanisms in response to various stimuli, how CCR6 expression is post-transcriptionally regulated in Th17 cells is unknown. Here, using RNA-binding protein HuR conditional knock-out (KO) and wild-type (WT) mice, we present evidence that HuR post-transcriptionally regulates CCR6 expression by binding to and stabilizing Ccr6 mRNA and by promoting CCR6 translation. We also found that HuR down-regulates several microRNA expressions, which could target the 3\u27-UTR of Ccr6 mRNA for decay. Accordingly, knock-out of HuR reduced CCR6 expression on Th17 cells and impaired their migration to CNS compared with the response of WT Th17 cells and thereby ameliorated EAE. Together, these findings highlight how HuR contributes to Th17 cell-mediated autoimmune neuroinflammation and support the notion that targeting HuR might be a potential therapeutic intervention for managing autoimmune disorders of the CNS

The static allometry of sexual and non-sexual traits in vervet monkeys

Sexual traits vary tremendously in static allometry. This variation may be explained in part by body size-related differences in the strength of selection. We tested this hypothesis in two populations of vervet monkeys, using estimates of the level of condition dependence for different morphological traits as a proxy for body size-related variation in the strength of selection. In support of the hypothesis, we found that the steepness of allometric slopes increased with the level of condition dependence. One trait of particular interest, the penis, had shallow allometric slopes and low levels of condition dependence, in agreement with one of the most consistent patterns yet detected in the study of allometry, namely that of genitalia exhibiting shallow allometries.This research was supported by NIH grant R01RR0163009

Needed Research on the Englishes of Appalachia

Information about the 79th annual meeting of the Southeastern Conference on Linguistics (SECOL) organized by Jennifer Cramer at the University of Kentucky on April 2012 in Lexington, Kentucky. Topics discussed at the meeting includes current state of research studies on linguistic processes in Appalachia, traditional dialectological and ethnographic. The meeting also featured panel experts including Bridget L. Anderson, Michael Montgomery and Walt Wolfram

Evidence of Differential Effects of Vitamin D Receptor Variants on Epithelial Ovarian Cancer Risk by Predicted Vitamin D Status

Introduction: Experimental studies suggest vitamin D inhibits ovarian carcinogenesis. Yet, epidemiologic studies of ovarian cancer risk and lifestyle correlates of vitamin D status, plasma 25-hydroxyvitamin D [25(OH)D], or vitamin D receptor (VDR) variants have been inconsistent. Objective: To evaluate VDR genetic associations by high vs. low predicted 25(OH)D, scores derived from known determinants of plasma 25(OH)D. To assess ovarian cancer associations with variants identified in genome-wide association studies (GWAS) of plasma 25(OH)D. Methods: We genotyped up to seven VDR and eight 25(OH)D GWAS variants in the Nurses’ Health Studies (562 cases, 1,553 controls) and New England Case–Control study (1,821 cases, 1,870 controls). We estimated haplotype scores using expectation-maximization-based algorithms. We used unconditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CI). We combined study results using DerSimonian and Laird meta-analysis. Results: Ovarian cancer risk increased per A allele of rs7975232 (VDR; OR = 1.12, 95% CI = 1.01–1.25) among all women. When stratified by predicted 25(OH)D, ovarian cancer was associated with rs731236 (VDR; per C allele OR = 1.31) and rs7975232 (OR = 1.38) among women with high predicted 25(OH)D, but not among women with low levels (P ≤ 0.009). We also observed heterogeneity by predicted 25(OH)D for the ovarian cancer association with VDR 3′ end haplotypes (P = 0.009). Of 25(OH)D-associated GWAS loci, rs7041 was associated with reduced ovarian cancer risk (per T allele OR = 0.92, 95% CI = 0.85-0.99), which did not differ by predicted 25(OH)D status. Conclusion: Our study suggests an influence of VDR 3′ end variants on ovarian cancer risk may be observed in women with high predicted 25(OH)D, which remained even after taking multiple comparisons into consideration. Future studies are needed to confirm our results and explore further the relation between vitamin D exposure, genetic variants, and ovarian cancer risk

Beta-alanine supplementation and high-intensity interval training augments metabolic adaptations and endurance performance in college-aged men

A randomized, double-blind, placebo-controlled study was conducted to evaluate the effects β-alanine supplementation and high-intensity interval training (HIIT) on endurance performance

Pre-workout consumption of Celsius® enhances the benefits of chronic exercise on body composition and cardiorespiratory fitness

The functional beverage Celsius®, has recently been shown, after acute and chronic (28 days) consumption, to increase resting metabolism and serum blood markers of lipolysis in healthy, college-aged men and women. The purpose of this study was to examine the combined effects of a 10-week exercise program while consuming Celsius® on body composition and cardiorespiratory fitness changes in sedentary men and women

Effects of β-alanine supplementation and high-intensity interval training on endurance performance and body composition in men; a double-blind trial

Background: Intermittent bouts of high-intensity exercise result in diminished stores of energy substrates, followed by an accumulation of metabolites, promoting chronic physiological adaptations. In addition, β-alanine has been accepted has an effective physiological hydrogen ion (H+) buffer. Concurrent high-intensity interval training (HIIT) and β-alanine supplementation may result in greater adaptations than HIIT alone. The purpose of the current study was to evaluate the effects of combining β-alanine supplementation with high-intensity interval training (HIIT) on endurance performance and aerobic metabolism in recreationally active college-aged men. Methods: Forty-six men (Age: 22.2 ± 2.7 yrs; Ht: 178.1 ± 7.4 cm; Wt: 78.7 ± 11.9; VO2peak: 3.3 ± 0.59 l·min-1) were assessed for peak O2 utilization (VO2peak), time to fatigue (VO2TTE), ventilatory threshold (VT), and total work done at 110% of pre-training VO2peak (TWD). In a double-blind fashion, all subjects were randomly assigned into one either a placebo (PL – 16.5 g dextrose powder per packet; n = 18) or β-alanine (BA – 1.5 g β-alanine plus 15 g dextrose powder per packet; n = 18) group. All subjects supplemented four times per day (total of 6 g/day) for the first 21-days, followed by two times per day (3 g/day) for the subsequent 21 days, and engaged in a total of six weeks of HIIT training consisting of 5–6 bouts of a 2:1 minute cycling work to rest ratio. Results: Significant improvements in VO2peak, VO2TTE, and TWD after three weeks of training were displayed (p \u3c 0.05). Increases in VO2peak, VO2TTE, TWD and lean body mass were only significant for the BA group after the second three weeks of training. Conclusion: The use of HIIT to induce significant aerobic improvements is effective and efficient. Chronic BA supplementation may further enhance HIIT, improving endurance performance and lean body mass

Effects of β-alanine supplementation and high-intensity interval training on endurance performance and body composition in men; a double-blind trial

Background: Intermittent bouts of high-intensity exercise result in diminished stores of energy substrates, followed by an accumulation of metabolites, promoting chronic physiological adaptations. In addition, β-alanine has been accepted has an effective physiological hydrogen ion (H+) buffer. Concurrent high-intensity interval training (HIIT) and β-alanine supplementation may result in greater adaptations than HIIT alone. The purpose of the current study was to evaluate the effects of combining β-alanine supplementation with high-intensity interval training (HIIT) on endurance performance and aerobic metabolism in recreationally active college-aged men. Methods: Forty-six men (Age: 22.2 ± 2.7 yrs; Ht: 178.1 ± 7.4 cm; Wt: 78.7 ± 11.9; VO2peak: 3.3 ± 0.59 l·min-1) were assessed for peak O2 utilization (VO2peak), time to fatigue (VO2TTE), ventilatory threshold (VT), and total work done at 110% of pre-training VO2peak (TWD). In a double-blind fashion, all subjects were randomly assigned into one either a placebo (PL – 16.5 g dextrose powder per packet; n = 18) or β-alanine (BA – 1.5 g β-alanine plus 15 g dextrose powder per packet; n = 18) group. All subjects supplemented four times per day (total of 6 g/day) for the first 21-days, followed by two times per day (3 g/day) for the subsequent 21 days, and engaged in a total of six weeks of HIIT training consisting of 5–6 bouts of a 2:1 minute cycling work to rest ratio. Results: Significant improvements in VO2peak, VO2TTE, and TWD after three weeks of training were displayed (p < 0.05). Increases in VO2peak, VO2TTE, TWD and lean body mass were only significant for the BA group after the second three weeks of training. Conclusion: The use of HIIT to induce significant aerobic improvements is effective and efficient. Chronic BA supplementation may further enhance HIIT, improving endurance performance and lean body mass