THE RELATIONSHIP BETWEEN MUSCULOSKELETAL STRENGTH, PHYSIOLOGICAL CHARACTERISTICS, AND KNEE KINESTHESIA FOLLOWING FATIGUING EXERCISE

Fatiguing exercise may result in impaired functional joint stability and increased risk of unintentional injury. While there are several musculoskeletal and physiological characteristics related to fatigue onset, their relationship with proprioceptive changes following fatigue has not been examined. The purpose of this study was to establish the relationship between musculoskeletal and physiological characteristics and changes in proprioception, measured by threshold to detect passive motion (TTDPM), following fatiguing exercise. Twenty, physically active females participated (age: 28.65 ± 5.6 years, height: 165.6 ± 4.3 cm, weight: 61.8 ± 8.0 kg, BMI: 22.5± 2.3 kg/m2, BF: 23.3 ± 5.4%). During Visit 1, subjects completed an exercise history and 24-hour dietary questionnaire, and body composition, TTDPM familiarization, isokinetic knee strength, and maximal oxygen uptake/lactate threshold assessments. During Visit 2, subjects completed TTDPM and isometric knee strength testing prior to and following a fatiguing exercise protocol. Wilcoxon signed rank tests determined TTDPM and isometric knee strength changes from pre- to post- fatigue. Spearman’s rho correlation coefficients determined the relationship between strength and physiological variables with pre- to post-fatigue changes in TTDPM and with pre-fatigue and post-fatigue TTDPM in extension and flexion (α=0.05). No significant differences were demonstrated from pre-fatigue to post-fatigue TTDPM despite a significant decrease in isometric knee flexion strength (P<0.01) and flexion/extension ratio (P<0.05) following fatigue. No significant correlations were observed between strength or physiological variables and changes in TTDPM from pre- to post-fatigue in extension or flexion. Flexion/extension ratio was significantly correlated with pre-fatigue TTDPM in extension (r=-0.231, P<0.05). Peak oxygen uptake was significantly correlated with pre-fatigue (r=-0.500, P<0.01) and post-fatigue (r=-0.520, P<0.05) TTDPM in extension. No significant relationships were demonstrated between musculoskeletal and physiological characteristics and changes in TTDPM following fatigue. The results suggest that highly trained individuals may have better proprioception, and that the high fitness level of subjects in this investigation may have contributed to absence of TTDPM deficits following fatigue despite reaching a high level of perceptual and physiological fatigue. Future studies should consider various subject populations, other musculoskeletal strength characteristics, and different modalities of proprioception to determine the most important contributions to proprioceptive changes following fatigue

Role of Polarized G Protein Signaling in Tracking Pheromone Gradients

SummaryYeast cells track gradients of pheromones to locate mating partners. Intuition suggests that uniform distribution of pheromone receptors over the cell surface would yield optimal gradient sensing. However, yeast cells display polarized receptors. The benefit of such polarization was unknown. During gradient tracking, cell growth is directed by a patch of polarity regulators that wanders around the cortex. Patch movement is sensitive to pheromone dose, with wandering reduced on the up-gradient side of the cell, resulting in net growth in that direction. Mathematical modeling suggests that active receptors and associated G proteins lag behind the polarity patch and act as an effective drag on patch movement. In vivo, the polarity patch is trailed by a G protein-rich domain, and this polarized distribution of G proteins is required to constrain patch wandering. Our findings explain why G protein polarization is beneficial and illuminate a novel mechanism for gradient tracking

Impact of Booster Breaks and Computer Prompts on Physical Activity and Sedentary Behavior Among Desk-Based Workers: A Cluster-Randomized Controlled Trial

Introduction The 15-minute work break provides an opportunity to promote health, yet few studies have examined this part of the workday. We studied physical activity and sedentary behavior among office workers and compared the results of the Booster Break program with those of a second intervention and a control group to determine whether the Booster Break program improved physical and behavioral health outcomes. Methods We conducted a 3-arm, cluster-randomized controlled trial at 4 worksites in Texas from 2010 through 2013 to compare a group-based, structured Booster Break program to an individual-based computer-prompt intervention and a usual-break control group; we analyzed physiologic, behavioral, and employee measures such as work social support, quality of life, and perceived stress. We also identified consistent and inconsistent attendees of the Booster Break sessions. Results We obtained data from 175 participants (mean age, 43 y; 67% racial/ethnic minority). Compared with the other groups, the consistent Booster Break attendees had greater weekly pedometer counts (P \u3c .001), significant decreases in sedentary behavior and self-reported leisure-time physical activity (P \u3c .001), and a significant increase in triglyceride concentrations (P = .02) (levels remained within the normal range). Usual-break participants significantly increased their body mass index, whereas Booster Break participants maintained body mass index status during the 6 months. Overall, Booster Break participants were 6.8 and 4.3 times more likely to have decreases in BMI and weekend sedentary time, respectively, than usual-break participants. Conclusion Findings varied among the 3 study groups; however, results indicate the potential for consistent attendees of the Booster Break intervention to achieve significant, positive changes related to physical activity, sedentary behavior, and body mass index

Overview of Grid-Scale Machinery-Based Energy Storage Technologies

TutorialGrid-scale energy storage is needed to smooth variable renewable power sources and enable deep penetration of renewable power generators into the energy mix. There are many existing or developing machinery-based energy storage systems, including pumped hydro, flywheels, compressed air, gravitational, liquid air, pumped thermal, and various thermochemical technologies such as hydrogen, ammonia, synthetic natural gas, or sulfur. This tutorial reviews all of these technologies including basic working principles, role of turbomachinery, hybridization with existing power generators, state of development, advantages and disadvantages relative to other technologies, and research & development needs for system improvements and commercialization

Applying phylogenomics to understand the emergence of Shiga Toxin producing Escherichia coli O157:H7 strains causing severe human disease in the United Kingdom

Shiga Toxin producing Escherichia coli (STEC) O157:H7 is a recently emerged zoonotic pathogen with considerable morbidity. Since the serotype emerged in the 1980s, research has focussed on unravelling the evolutionary events from the E. coli O55:H7 ancestor to the contemporaneous globally dispersed strains. In this study the genomes of over 1000 isolates from human clinical cases and cattle, spanning the history of STEC O157:H7 in the United Kingdom were sequenced. Phylogenetic analysis reveals the ancestry, key acquisition events and global context of the strains. Dated phylogenies estimate the time to the most recent common ancestor of the current circulating global clone to 175 years ago, followed by rapid diversification. We show the acquisition of specific virulence determinates occurred relatively recently and coincides with its recent detection in the human population. Using clinical outcome data from 493 cases of STEC O157:H7 we assess the relative risk of severe disease including HUS from each of the defined clades in the population and show the dramatic effect Shiga toxin complement has on virulence. We describe two strain replacement events that have occurred in the cattle population in the UK over the last 30 years; one resulting in a highly virulent strain that has accounted for the majority of clinical cases in the UK over the last decade. This work highlights the need to understand the selection pressures maintaining Shiga-toxin encoding bacteriophages in the ruminant reservoir and the study affirms the requirement for close surveillance of this pathogen in both ruminant and human populations

Cancer-associated mutations reveal a novel role for EpCAM as an inhibitor of cathepsin-L and tumor cell invasion

BACKGROUND: EpCAM (Epithelial cell adhesion molecule) is often dysregulated in epithelial cancers. Prior studies implicate EpCAM in the regulation of oncogenic signaling pathways and epithelial-to-mesenchymal transition. It was recently demonstrated that EpCAM contains a thyroglobulin type-1 (TY-1) domain. Multiple proteins with TY-1 domains are known to inhibit cathepsin-L (CTSL), a cysteine protease that promotes tumor cell invasion and metastasis. Analysis of human cancer sequencing studies reveals that somatic EpCAM mutations are present in up to 5.1% of tested tumors. METHODS: The Catalogue of Somatic Mutations in Cancer (COSMIC) database was queried to tabulate the position and amino acid changes of cancer associated EpCAM mutations. To determine how EpCAM mutations affect cancer biology we studied C66Y, a damaging TY-1 domain mutation identified in liver cancer, as well as 13 other cancer-associated EpCAM mutations. In vitro and in vivo models were used to determine the effect of wild type (WT) and mutant EpCAM on CTSL activity and invasion. Immunoprecipitation and localization studies tested EpCAM and CTSL protein binding and determined compartmental expression patterns of EpCAM mutants. RESULTS: We demonstrate that WT EpCAM, but not C66Y EpCAM, inhibits CTSL activity in vitro, and the TY-1 domain of EpCAM is responsible for this inhibition. WT EpCAM, but not C66Y EpCAM, inhibits tumor cell invasion in vitro and lung metastases in vivo. In an extended panel of human cancer cell lines, EpCAM expression is inversely correlated with CTSL activity. Previous studies have demonstrated that EpCAM germline mutations can prevent EpCAM from being expressed at the cell surface. We demonstrate that C66Y and multiple other EpCAM cancer-associated mutations prevent surface expression of EpCAM. Cancer-associated mutations that prevent EpCAM cell surface expression abrogate the ability of EpCAM to inhibit CTSL activity and tumor cell invasion. CONCLUSIONS: These studies reveal a novel role for EpCAM as a CTSL inhibitor, confirm the functional relevance of multiple cancer-associated EpCAM mutations, and suggest a therapeutic vulnerability in cancers harboring EpCAM mutations

A massive stellar bulge in a regularly rotating galaxy 1.2 billion years after the Big Bang.

Cosmological models predict that galaxies forming in the early Universe experience a chaotic phase of gas accretion and star formation, followed by gas ejection due to feedback processes. Galaxy bulges may assemble later via mergers or internal evolution. Here we present submillimeter observations (with spatial resolution of 700 parsecs) of ALESS 073.1, a starburst galaxy at redshift [Formula: see text] when the Universe was 1.2 billion years old. This galaxy's cold gas forms a regularly rotating disk with negligible noncircular motions. The galaxy rotation curve requires the presence of a central bulge in addition to a star-forming disk. We conclude that massive bulges and regularly rotating disks can form more rapidly in the early Universe than predicted by models of galaxy formation.ERC STF

Evaluating the QUIT-PRIMO clinical practice ePortal to increase smoker engagement with online cessation interventions: a national hybrid type 2 implementation study

BACKGROUND: Effective web-assisted tobacco interventions (WATIs) have been underutilized by smokers; moreover, despite practice guideline recommendations, clinical teams do not routinely refer smokers to WATIs. Our goal was to test a clinical practice innovation, an ePortal designed to change practice and patient behavior. Our hypotheses were that the integrated system would result in increased smoker referrals, with an automated follow-up system resulting in more smoker registrations and finally augmentations of the WATI would result in more smokers quitting at 6 months. METHODS: Practice ePortal Implementation Trial: Practices (n = 174) were randomized to an online practice ePortal with an e-referral tool to the WATI (e-referred smokers received automated email reminders from the practice) and with practice feedback reports with patient tracking and practice-to-patient secure messaging versus comparison (a paper referral prescription ). Implementation success was measured by the number of smokers referred and smokers registering. Clinical Effectiveness Trial: To estimate the effectiveness of the WATI components on 6-month smoking cessation, registered smokers were randomized into three groups: a state-of-the-art tailored WATI control [control], the WATI enhanced with proactive, pushed tailored email motivational messaging (messaging), and the WATI with messaging further enhanced with personal secure messaging with a tobacco treatment specialist and an online support group (personalized). RESULTS: Practice ePortal Trial results: A total of 4789 smokers were referred. The mean smokers referred per practice was not statistically different by group (ePortal 24.89 (SD 22.29) versus comparison 30.15 (SD 25.45), p = 0.15). The e-referral portal implementation program resulted in nearly triple the rate of smoker registration (31 % of all smokers referred registered online) versus comparison (11 %, p \u3c 0.001). Clinical Effectiveness Trial results: Active smokers randomized to the personalized group had a 6-month cessation rate of 25.2 %, compared with the messaging group (26.7 %) and the control (17 %). Next, when using an inverse probability weighted selection model to account for attrition, those randomized to the two groups that received motivational messaging (messaging or personalized) were more likely to quit than those in the control (p = 0.04). CONCLUSIONS: Among all smokers referred, the e-referral resulted in nearly threefold greater registrants (31 %) than paper (11 %). The practice ePortal smokers received multiple reminders (increasing registration opportunities), and the practices could track patient progress. The result was more smokers registering and, thus, more cessation opportunities. Combining the proactive referral and the WATI resulted in higher rates of smoking cessation. TRIAL REGISTRATION: Web-delivered Provider Intervention for Tobacco Control (QUIT-PRIMO) - a randomized controlled trial: NCT00797628