Minimal Differences Between Males and Females in Exercise-Induced Increase of Circulating T Cells Subsets in Older Adults

PURPOSE: To examine potential differences between older adult males and females’ acute post-exercise circulating T cell response. METHODS: Participants were healthy older adults with an average age of 63.0 ± 1.0 years (n= 24, females = 70.8%) and BMI of 24.7 ± 0.7 kg∙m-2. All females were post-menopausal. A single bout of cardiorespiratory exercise at ~70% heart rate reserve and a separate bout of eight resistance exercises at ~70% 1 repetition maximum were conducted at least one week apart. T cell count changes were determined via blood sample at rest and immediately post-exercise for each bout. Multi-color flow cytometry was used for T cell counts of each subset. Subsets in the project included CD3+, CD8+, and CD4+ naïve, central and effector memory, and cytotoxic T cells, as well as Th17 cells. Multilinear regression models were utilized to determine predictors and covariates of the exercise-induced T cell differences. RESULTS: In total, 16 T cell types were analyzed for response to both acute CRE and RE bouts of exercise. Although there was a varying response to each acute exercise bout, CD8+ EMRA T cell subset was the only one influenced by male (pre- to post-exercise difference: 56.41 ± 0.81 cells/mL) or female (pre- to post-exercise difference: 18.89 ± 0.27 cells/mL) sex in response to the CRE bout (sex difference p=0.0113). There were no other T cell subsets where the model selection included sex as a covariate. CONCUSSION: EMRA CD8+ T cells after a CRE bout were the only studied T cells with sex included in the model selection for post-exercise increase to either acute CRE or RE. Given the small effect size and it being the only effected T cell subset, it is possible that the sex influence is an artifact in the model. These results support that sex may not be considered a primary influence on post-exercise T cell response in either CRE or RE acute bouts for healthy older adults where all the females are post-menopausal

Impact of Camera and Lighting Position on Video Detection Precision

On well-illuminated approaches, vehicle headlight reflections on the pavement were observed to cause video detection units to activate early. This early activation results in a dramatic increase in the length of the effective vehicle detection zone. This observed variation in the effective length of the vehicle detection zone that varies by ambient lighting condition and camera placement presents a very serious impediment for traffic engineers to design vehicle extension intervals that operate correctly during day, night and transition periods. Furthermore, the stochastic variation in the length of the vehicle detection zone length has the potential to create driver expectancy issues. Tables are included that reports the observed average and range of detection zone length variations for 16 observed video cameras that were extensively calibrated by the manufacturer at the test site. The paper concludes by recommending near-side placement of video detection devices to reduce the stochastic variation in detection zone length

MAPPING QTL WITH COVARIATES

Quantitative trait loci (QTL) analysis is an effective tool for locating regions of the genome associated with a trait. Quantitative trait data are complex, and when statistically testing for the location of a QTL, the distribution of the test statistic is typically unknown. Historically, asymptotic thresholds have been difficult to derive for QTL analysis. Permutation testing has successfully provided significance thresholds for QTL analysis, but the need for exchangeability among the observations limits these empirically derived thresholds to simple linear models and does not permit the inclusion of important covariates in the model. We address the limitation of permutation theory for supplying empirically derived QTL significance threshold using a novel bootstrap threshold that is appropriate for multiple regression based interval mapping models. Simulation studies demonstrate that the proposed bootstrap thresholds improve detection and estimation of additive effects in QTL studies

Effect of the lysosomotropic agent chloroquine on mTORC1 activation and protein synthesis in human skeletal muscle

Background Previous work in HEK-293 cells demonstrated the importance of amino acid-induced mTORC1 translocation to the lysosomal surface for stimulating mTORC1 kinase activity and protein synthesis. This study tested the conservation of this amino acid sensing mechanism in human skeletal muscle by treating subjects with chloroquine—a lysosomotropic agent that induces in vitro and in vivo lysosome dysfunction. Methods mTORC1 signaling and muscle protein synthesis (MPS) were determined in vivo in a randomized controlled trial of 14 subjects (10 M, 4 F; 26 ± 4 year) that ingested 10 g of essential amino acids (EAA) after receiving 750 mg of chloroquine (CHQ, n = 7) or serving as controls (CON, n = 7; no chloroquine). Additionally, differentiated C2C12 cells were used to assess mTORC1 signaling and myotube protein synthesis (MyPS) in the presence and absence of leucine and the lysosomotropic agent chloroquine. Results mTORC1, S6K1, 4E-BP1 and rpS6 phosphorylation increased in both CON and CHQ 1 h post EAA ingestion (P \u3c 0.05). MPS increased similarly in both groups (CON, P = 0.06; CHQ, P \u3c 0.05). In contrast, in C2C12 cells, 1 mM leucine increased mTORC1 and S6K1 phosphorylation (P \u3c 0.05), which was inhibited by 2 mg/ml chloroquine. Chloroquine (2 mg/ml) was sufficient to disrupt mTORC1 signaling, and MyPS. Conclusions Chloroquine did not inhibit amino acid-induced activation of mTORC1 signaling and skeletal MPS in humans as it does in C2C12 muscle cells. Therefore, different in vivo experimental approaches are required for confirming the precise role of the lysosome and amino acid sensing in human skeletal muscle

Analysis of a Panel of 48 Cytokines in BAL Fluids Specifically Identifies IL-8 Levels as the Only Cytokine that Distinguishes Controlled Asthma from Uncontrolled Asthma, and Correlates Inversely with FEV1

We sought to identify cells and cytokines in bronchoalveolar lavage (BAL) fluids that distinguish asthma from healthy control subjects and those that distinguish controlled asthma from uncontrolled asthma. Following informed consent, 36 human subjects were recruited for this study. These included 11 healthy control subjects, 15 subjects with controlled asthma with FEV1≥80% predicted and 10 subjects with uncontrolled asthma with FEV1 2.4%) were a higher BAL fluid IL-8 levels, and a lower FEV1 in the latter group. By contrast, compared to eosinophil-normal asthma (eosinophils≤0.3%), eosinophil-high asthma (eosinophils>0.3%) had higher levels of IL-5, IL-13, IL-16, and PDGF-bb, but same neutrophil percentage, IL-8, and FEV1. Our results identify neutrophils and IL-8 are the only inflammatory components in BAL fluids that distinguish controlled asthma from uncontrolled asthma, and both correlate inversely with FEV1

Biochemical genesis of enzymatic and non-enzymatic post-translational modifications

Post-translational modifications (PTMs) alter protein structure, function, and localization and play a pivotal role in physiological and pathophysiological conditions. Many PTMs arise from endogenous metabolic intermediates and serve as sensors for metabolic feedback to maintain cell growth and homeostasis. A key feature to PTMs is their biochemical genesis, which can result from either non-enzymatic adduction (nPTMs) or through enzyme-catalyzed reactions (ePTMs). The abundance and site-specificity of PTMs are determined by dedicated classes of enzymes that add (writers) or remove (erasers) the chemical addition. In this review we will highlight the biochemical genesis and regulation of a few of the 700+ PTMs that have been identified.NIGMS12 month embargo; available online 24 November 2021This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

A Short-Term Paleolithic Dietary Intervention Does Not Alter Adipokines Linked to Adiposity

International Journal of Exercise Science 14(2): 113-122, 2021. The Paleolithic diet, characterized by an emphasis on hunter-gatherer type foods accompanied by an exclusion of grains, dairy products, and highly processed food items, is often promoted for weight loss and a reduction in cardiometabolic disease risk factors. Specific adipokines, such as adiponectin, omentin, nesfatin, and vaspin are reported to be dysregulated with obesity and may respond favorably to diet-induced fat loss. We aimed to evaluate the effects of an eight-week Paleolithic dietary intervention on circulating adiponectin, omentin, nesfatin, and vaspin in a cohort of physically inactive, but otherwise healthy adults. Methods: Seven inactive adults participated in eight weeks of adherence to the Paleolithic Diet. Fasting blood samples, anthropometric, and body composition data were collected from each participant pre- and post-intervention. Serum adiponectin, omentin, nesfatin, and vaspin were measured. Results: After eight weeks of following the Paleolithic diet, there were reductions (p\u3c0.05) in relative body fat (-4.4%), waist circumference (-5.9 cm), and sum of skinfolds (-36.8 mm). No changes were observed in waist to hip ratio (WHR), or in adiponectin, omentin, and nesfatin (p\u3e0.05), while serum vaspin levels for all participants were undetectable. Conclusions: It is possible that although eight weeks resulted in modest body composition changes, short-term fat loss will not induce changes in adiponectin, omentin, and nesfatin in apparently healthy adults. Larger, long-term intervention studies that examine Paleolithic diet-induced changes across sex, body composition, and in populations with metabolic dysregulation are warranted

Polymorphisms of immunity genes and susceptibility to otitis media in children.

Acute otitis media (OM) is a common disease which often develops through complex interactions between the host, the pathogen and environmental factors. We studied single nucleotide polymorphisms (SNPs) of genes involved in innate and adaptive immunity, and other host and environmental factors for their role in OM.Using Sequenom Massarray platform, 21 SNPs were studied in 653 children from prospective (n = 202) and retrospective (n = 451) cohorts. Data were analyzed for the relationship between SNPs and upper respiratory infection (URI) frequency, risk of acute OM during URI episodes, and proneness to recurrent OM.Increased risk for OM proneness was associated with CX3CR1 (Thr280Met) SNP and with a jointly interactive group of IL-10 (-1082) SNP, IL-1β (-511) wild type genotype and white race. Family history of OM proneness independently increased the risk for frequent URIs, OM occurrence during URI, and OM proneness. Additionally, IL-1β (-31) SNP was associated with increased risk for frequent URIs, but IL-10 (-592), IL-1β (-511), IL-5 (-746) and IL-8 (-251) SNPs were associated with decreased risk of URI.IL-1β (-31), CX3CR1 (Thr280Met), IL-10 (-1082) and IL-1β (-511) SNPs were associated with increased risk for frequent URIs or OM proneness