Tart cherry supplementation and recovery from strenuous exercise: a systematic review and meta-analysis: Tart cherry juice and recovery

The aim of this study was to determine the efficacy of tart cherry (TC) supplementation on recovery following strenuous exercise. A systematic review and meta-analysis were conducted using studies investigating TC supplementation on measures of muscle soreness, muscular strength, muscular power, creatine kinase, C-reactive protein, Interleukin-6, and tumor necrosis factor alpha. A literature search ending in July 2020 was conducted in three databases (SPORTDiscus, Web of Science, and PubMed). Data from 14 studies were extracted and pooled for analysis. Tart cherry supplementation had a small beneficial effect in reducing muscle soreness (effect size [ES] = −0.44, 95% confidence interval [CI] [−0.87, −0.02]). A moderate beneficial effect was observed for recovery of muscular strength (ES = −0.78, 95% CI [−1.11, −0.46]). A moderate effect was observed for muscular power (ES = −0.53, 95% CI [−0.77, −0.29]); a further subgroup analysis on this variable indicated a large effect of TC supplementation on recovery of jump height (ES = −0.82, 95% CI [−1.18, −0.45]) and a small significant effect of supplementation on sprint time (ES = −0.32, 95% CI [−0.60, −0.04]). A small effect was observed for both C-reactive protein (ES = −0.46, 95% CI [−0.93, −0.00]) and Interleukin-6 (ES = −0.35, 95% CI [−0.68, −0.02]. No significant effects were observed for creatine kinase and tumor necrosis factor alpha. These results indicate that the consumption of a TC supplement can aid aspects of recovery from strenuous exercise

A 4-week, lifestyle-integrated, home-based exercise training programme elicits improvements in physical function and lean mass in older men and women: a pilot study

Background: Developing alternative exercise programmes that can alleviate certain barriers to exercise such as psychological, environmental or socio-economical barriers, but provide similar physiological benefits e.g. increases in muscle mass and strength, is of grave importance. This pilot study aimed to assess the efficacy of an unsupervised, 4-week, whole-body home-based exercise training (HBET) programme, incorporated into daily living activities, on skeletal muscle mass, power and strength. Methods: Twelve healthy older volunteers (63±3 years, 7 men: 5 women, BMI: 29±1 kg/m²) carried out the 4-week “lifestyle-integrated” HBET of 8 exercises, 3x12 repetitions each, every day. Before and after HBET, a number of physical function tests were carried out: unilateral leg extension 1-RM (one- repetition maximum), MVC (maximal voluntary contraction) leg extension, lower leg muscle power (via Nottingham Power Rig), handgrip strength and SPPBT (short physical performance battery test). A D3-Creatine method was used for assessment of whole-body skeletal muscle mass, and ultrasound was used to measure the quadriceps cross-sectional area (CSA) and vastus lateralis muscle thickness. Results: Four weeks HBET elicited significant (p<0.05) improvements in leg muscle power (276.7±38.5 vs. 323.4±43.4 W), maximal voluntary contraction (60°: 154.2±18.4 vs. 168.8±15.2 Nm, 90°: 152.1±10.5 vs. 159.1±11.4 Nm) and quadriceps CSA (57.5±5.4 vs. 59.0±5.3 cm2), with a trend for an increase in leg strength (1-RM: 45.7±5.9 vs. 49.6±6.0 kg, P=0.08). This was despite there being no significant differences in whole-body skeletal muscle mass, as assessed via D3-Creatine. Conclusions: This study demonstrates that increases in multiple aspects of muscle function can be achieved in older adults with just 4-weeks of “lifestyle-integrated” HBET, with a cost-effective means. This training mode may prove to be a beneficial alternative for maintaining and/or improving muscle mass and function in older adults

Tart cherry supplementation and recovery from strenuous exercise: a systematic review and meta-analysis

The aim of this study was to determine the efficacy of tart cherry supplementation on recovery following strenuous exercise. A systematic review and meta-analysis was conducted using studies investigating tart cherry supplementation on measures of muscle soreness, muscular strength, muscular power, creatine kinase (CK), C reactive protein (CRP), Interleukin-6 (IL-6) and tumour necrosis factor alpha (TNFα). A literature search ending in July 2020 was conducted in 3 databases (SPORTDiscus, Web of Science and Pubmed). Data from 14 studies was extracted and pooled for analysis. Tart cherry supplementation had a small beneficial effect in reducing muscle soreness (ES = -0.44, 95% CI [-0.87, -0.02]). A moderate beneficial effect was observed for recovery of muscular strength (ES = -0.78, 95% CI [-1.11, -0.46]). A moderate effect was observed for muscular power (ES = -0.53, 95% CI [-0.77, -0.29]), a further subgroup analysis on this variable indicated a large effect of tart cherry supplementation on recovery of jump height (ES = -0.82, 95% CI [-1.18, -0.45]) and a small significant effect of supplementation on sprint time (ES = -0.32, 95% CI [-0.60, -0.04]). A small effect was observed for both CRP (ES = -0.46, 95% CI [-0.93, -0.00]) and IL-6 (ES = -0.35, 95% CI [-0.68, -0.02]. No significant effects were observed for CK, and TNFα. These results indicate that the consumption of a tart cherry supplement can aid aspects of recovery from strenuous exercise

Spire, an Actin Nucleation Factor, Regulates Cell Division during Drosophila Heart Development

The Drosophila dorsal vessel is a beneficial model system for studying the regulation of early heart development. Spire (Spir), an actin-nucleation factor, regulates actin dynamics in many developmental processes, such as cell shape determination, intracellular transport, and locomotion. Through protein expression pattern analysis, we demonstrate that the absence of spir function affects cell division in Myocyte enhancer factor 2-, Tinman (Tin)-, Even-skipped- and Seven up (Svp)-positive heart cells. In addition, genetic interaction analysis shows that spir functionally interacts with Dorsocross, tin, and pannier to properly specify the cardiac fate. Furthermore, through visualization of double heterozygous embryos, we determines that spir cooperates with CycA for heart cell specification and division. Finally, when comparing the spir mutant phenotype with that of a CycA mutant, the results suggest that most Svp-positive progenitors in spir mutant embryos cannot undergo full cell division at cell cycle 15, and that Tin-positive progenitors are arrested at cell cycle 16 as double-nucleated cells. We conclude that Spir plays a crucial role in controlling dorsal vessel formation and has a function in cell division during heart tube morphogenesis

Clinical impact of genomic testing in patients with suspected monogenic kidney disease

Purpose: To determine the diagnostic yield and clinical impact of exome sequencing (ES) in patients with suspected monogenic kidney disease. Methods: We performed clinically accredited singleton ES in a prospectively ascertained cohort of 204 patients assessed in multidisciplinary renal genetics clinics at four tertiary hospitals in Melbourne, Australia. Results: ES identified a molecular diagnosis in 80 (39%) patients, encompassing 35 distinct genetic disorders. Younger age at presentation was independently associated with an ES diagnosis (p < 0.001). Of those diagnosed, 31/80 (39%) had a change in their clinical diagnosis. ES diagnosis was considered to have contributed to management in 47/80 (59%), including negating the need for diagnostic renal biopsy in 10/80 (13%), changing surveillance in 35/80 (44%), and changing the treatment plan in 16/80 (20%). In cases with no change to management in the proband, the ES result had implications for the management of family members in 26/33 (79%). Cascade testing was subsequently offered to 40/80 families (50%). Conclusion: In this pragmatic pediatric and adult cohort with suspected monogenic kidney disease, ES had high diagnostic and clinical utility. Our findings, including predictors of positive diagnosis, can be used to guide clinical practice and health service design

Chromatin States Accurately Classify Cell Differentiation Stages

Gene expression is controlled by the concerted interactions between transcription factors and chromatin regulators. While recent studies have identified global chromatin state changes across cell-types, it remains unclear to what extent these changes are co-regulated during cell-differentiation. Here we present a comprehensive computational analysis by assembling a large dataset containing genome-wide occupancy information of 5 histone modifications in 27 human cell lines (including 24 normal and 3 cancer cell lines) obtained from the public domain, followed by independent analysis at three different representations. We classified the differentiation stage of a cell-type based on its genome-wide pattern of chromatin states, and found that our method was able to identify normal cell lines with nearly 100% accuracy. We then applied our model to classify the cancer cell lines and found that each can be unequivocally classified as differentiated cells. The differences can be in part explained by the differential activities of three regulatory modules associated with embryonic stem cells. We also found that the “hotspot” genes, whose chromatin states change dynamically in accordance to the differentiation stage, are not randomly distributed across the genome but tend to be embedded in multi-gene chromatin domains, and that specialized gene clusters tend to be embedded in stably occupied domains

The Drosophila afadin homologue Canoe regulates linkage of the actin cytoskeleton to adherens junctions during apical constriction

Cadherin-based adherens junctions (AJs) mediate cell adhesion and regulate cell shape change. The nectin–afadin complex also localizes to AJs and links to the cytoskeleton. Mammalian afadin has been suggested to be essential for adhesion and polarity establishment, but its mechanism of action is unclear. In contrast, Drosophila melanogaster’s afadin homologue Canoe (Cno) has suggested roles in signal transduction during morphogenesis. We completely removed Cno from embryos, testing these hypotheses. Surprisingly, Cno is not essential for AJ assembly or for AJ maintenance in many tissues. However, morphogenesis is impaired from the start. Apical constriction of mesodermal cells initiates but is not completed. The actomyosin cytoskeleton disconnects from AJs, uncoupling actomyosin constriction and cell shape change. Cno has multiple direct interactions with AJ proteins, but is not a core part of the cadherin–catenin complex. Instead, Cno localizes to AJs by a Rap1- and actin-dependent mechanism. These data suggest that Cno regulates linkage between AJs and the actin cytoskeleton during morphogenesis

MuRF1 activity is present in cardiac mitochondria and regulates reactive oxygen species production in vivo

Erratum: https://link.springer.com/article/10.1007/s10863-014-9597-1MuRF1 is a previously reported ubiquitin-ligase found in striated muscle that targets troponin I and myosin heavy chain for degradation. While MuRF1 has been reported to interact with mitochondrial substrates in yeast two-hybrid studies, no studies have identified MuRF1’s role in regulating mitochondrial function to date. In the present study, we measured cardiac mitochondrial function from isolated permeabilized muscle fibers in previously phenotyped MuRF1 transgenic and MuRF1−/− mouse models to determine the role of MuRF1 in intermediate energy metabolism and ROS production. We identified a significant decrease in reactive oxygen species production in cardiac muscle fibers from MuRF1 transgenic mice with increased α-MHC driven MuRF1 expression. Increased MuRF1 expression in ex vivo and in vitro experiments revealed no alterations in the respiratory chain complex I and II function. Working perfusion experiments on MuRF1 transgenic hearts demonstrated significant changes in glucose oxidation. This is an factual error as written; however, total oxygen consumption was decreased. This data provides evidence for MuRF1 as a novel regulator of cardiac ROS, offering another mechanism by which increased MuRF1 expression may be cardioprotective in ischemia reperfusion injury, in addition to its inhibition of apoptosis via proteasome-mediate degradation of c-Jun. The lack of mitochondrial function phenotype identified in MuRF1−/− hearts may be due to the overlapping interactions of MuRF1 and MuRF2 with energy regulating proteins found by yeast two-hybrid studies reported here, implying a duplicity in MuRF1 and MuRF2’s regulation of mitochondrial function.Funding support from Medical Research Council, United Kingdom; National Institutes of Health, United States; British Heart Foundation, United Kingdo

Fine mapping of type 1 diabetes susceptibility loci and evidence for colocalization of causal variants with lymphoid gene enhancers.

Genetic studies of type 1 diabetes (T1D) have identified 50 susceptibility regions, finding major pathways contributing to risk, with some loci shared across immune disorders. To make genetic comparisons across autoimmune disorders as informative as possible, a dense genotyping array, the Immunochip, was developed, from which we identified four new T1D-associated regions (P < 5 × 10(-8)). A comparative analysis with 15 immune diseases showed that T1D is more similar genetically to other autoantibody-positive diseases, significantly most similar to juvenile idiopathic arthritis and significantly least similar to ulcerative colitis, and provided support for three additional new T1D risk loci. Using a Bayesian approach, we defined credible sets for the T1D-associated SNPs. The associated SNPs localized to enhancer sequences active in thymus, T and B cells, and CD34(+) stem cells. Enhancer-promoter interactions can now be analyzed in these cell types to identify which particular genes and regulatory sequences are causal.This research uses resources provided by the Type 1 Diabetes Genetics Consortium, a collaborative clinical study sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), the National Institute of Allergy and Infectious Diseases (NIAID), the National Human Genome Research Institute (NHGRI), the National Institute of Child Health and Human Development (NICHD) and JDRF and supported by grant U01 DK062418 from the US National Institutes of Health. Further support was provided by grants from the NIDDK (DK046635 and DK085678) to P.C. and by a joint JDRF and Wellcome Trust grant (WT061858/09115) to the Diabetes and Inflammation Laboratory at Cambridge University, which also received support from the NIHR Cambridge Biomedical Research Centre. ImmunoBase receives support from Eli Lilly and Company. C.W. and H.G. are funded by the Wellcome Trust (089989). The Cambridge Institute for Medical Research (CIMR) is in receipt of a Wellcome Trust Strategic Award (100140). We gratefully acknowledge the following groups and individuals who provided biological samples or data for this study. We obtained DNA samples from the British 1958 Birth Cohort collection, funded by the UK Medical Research Council and the Wellcome Trust. We acknowledge use of DNA samples from the NIHR Cambridge BioResource. We thank volunteers for their support and participation in the Cambridge BioResource and members of the Cambridge BioResource Scientific Advisory Board (SAB) and Management Committee for their support of our study. We acknowledge the NIHR Cambridge Biomedical Research Centre for funding. Access to Cambridge BioResource volunteers and to their data and samples are governed by the Cambridge BioResource SAB. Documents describing access arrangements and contact details are available at http://www.cambridgebioresource.org.uk/. We thank the Avon Longitudinal Study of Parents and Children laboratory in Bristol, UK, and the British 1958 Birth Cohort team, including S. Ring, R. Jones, M. Pembrey, W. McArdle, D. Strachan and P. Burton, for preparing and providing the control DNA samples. This study makes use of data generated by the Wellcome Trust Case Control Consortium, funded by Wellcome Trust award 076113; a full list of the investigators who contributed to the generation of the data is available from http://www.wtccc.org.uk/.This is the author accepted manuscript. The final version is available via NPG at http://www.nature.com/ng/journal/v47/n4/full/ng.3245.html