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This study aimed to elucidate the effects of change in estrogen during the menstrual cycle and menopause on shear-mediated dilation of the internal carotid artery (ICA), a potential index of cerebrovascular endothelial function. Shear-mediated dilation of the ICA and serum estradiol were measured in 11 premenopausal (Pre-M, 21 ± 1 yr), 13 perimenopausal (Peri-M, 49 ± 2 yr), and 10 postmenopausal (Post-M, 65 ± 7 yr) women. Measurements were made twice within the Pre-M group at their early follicular (EF, lower estradiol) and late follicular (LF, higher estradiol) phases. Shear-mediated dilation was induced by 3 min of hypercapnia (target PETCO2 + 10 mmHg from individual baseline) and was calculated as the percent rise in peak diameter relative to baseline diameter. ICA diameter and blood velocity were simultaneously measured by Doppler ultrasound. In Pre-M, shear-mediated dilation was higher during the LF phase than during the EF phase (P less then 0.01). Comparing all groups, shear-mediated dilation was redpausal women. Shear-mediated dilation of the ICA was increased from the low- to high-estradiol phases in naturally cycling premenopausal women and was reduced with advancing menopause stages. Furthermore, lower estradiol was associated with reduced shear-mediated dilation of the ICA, independent of age.Brain capillary pericytes have been suggested to play a role in the regulation of cerebral blood flow under physiological and pathophysiological conditions. ATP has been shown to cause constriction of capillaries under ischemic conditions and suggested to be involved in the "no-reflow" phenomenon. To investigate the effects of extracellular ATP on pericyte cell contraction, we studied purinergic receptor activation of cultured bovine brain capillary pericytes. We measured intracellular Ca2+ concentration ([Ca2+]i) responses to purinergic agonists with the fluorescent indicators fura-2 and Cal-520 and estimated contraction of pericytes as relative change in cell area, using real-time confocal imaging. Addition of ATP caused an increase in cytosolic calcium and contraction of the brain capillary pericytes, both reversible and inhibited by the purinergic receptor antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS). Furthermore, we demonstrated that ATP-induced contraction could be eliminated lation of cerebral blood flow. We show that extracellular ATP causes contraction of primary brain pericytes by stimulation of purinergic receptors and subsequent release of intracellular Ca2+ concentration ([Ca2+]i). The contraction is mainly mediated through activation of P2Y-receptor subtypes, including P2Y1 and P2Y2. These findings add more mechanistic understanding of the role of pericytes in regulation of capillary blood flow. click here ATP was earlier suggested to be involved in capillary constriction in brain pathologies, and our study gives a detailed account of a part of this important mechanism.Protein disulfide isomerases (PDIs) are pivotal protein folding catalysts in the endoplasmic reticulum (ER) through formation of disulfide bond, isomerization, and inhibition of misfolded protein aggregation. When protein folding capacity is overwhelmed by the demands during transitions between growth phases or under environmental changes, the accumulation of unfolded or misfolded proteins in the ER triggers ER stress. However, little is known about the PDI gene family in the model legume Medicago truncatula, especially the responses to ER stress. Therefore, we identified 17 putative PDI genes from the genome of M. truncatula and present their gene and protein structures, phylogenetic relationships, chromosomal distributions, and synteny analysis with the orthologs in four other eudicot species, including Arabidopsis thaliana, Glycine max, Brassica rapa, and Vitis vinifera. Moreover, expression profiles derived from transcriptome data showed distinct expression patterns of MtPDI genes among plant organs, while real-time quantitative PCR analysis and data from the proteome revealed the potential roles of MtPDI genes in response to ER stress. Our study provides a foundation for further investigations of the biological roles of PDI genes in Medicago, especially their roles in response to ER stress.Objectives While injuries among collegiate athletes are common and well-studied, there have been no studies comparing which sports and injury types have the highest operation rates. This information would be valuable for athlete governing bodies and providers to improve player safety. Our hypothesis was the surgery incidence rates vary substantially between sports and injury types, with football and knee injuries representing the sport and injury type with the highest respective surgery rates. Methods This was a descriptive epidemiology study of all injuries requiring surgery as recorded in the National Collegiate Athletic Association (NCAA) Injury Surveillance Program (ISP) for academic years 2004-2005 to 2013-2014. Surgery incidence rates (and 95% confidence intervals, CI) were calculated for each sport (per 10,000 athletic exposures [AE]) and for the most common injury types, by academic year. In addition, absolute numbers of performed surgeries were calculated as well as rates of return to sport. Results Sports with the highest surgery incidence rate (per 10,000 AEs) were women's gymnastics (8.9; 95% CI 7.2-10.9), men's football (6.1; 95% CI 5.8-6.4), and men's wrestling (5.3; 95% CI 4.5-6.3). Absolute numbers of injury-related surgeries performed were greatest for men's football (n = 31,043), women's basketball (6,625), and men's basketball (5,717). Anterior cruciate ligament tears had the greatest surgery incidence rate per 100,000 AEs for all sports combined (7.95; 95% CI = 7.5 to 8.5), and also represented the injuries with the lowest rate of return to sport. Conclusion Women's gymnastics, men's football, and men's and women's basketball are NCAA sports with an elevated risk of injury requiring of surgery. The results from this study can guide the NCAA and providers regarding which sports should be the focus of future research, new injury prevention strategies, and healthcare personnel allocation during events.

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