Increased Nitric Oxide and Attenuated Diastolic Blood Pressure Variability in African Americans with Mildly Impaired Renal Function

We investigated the relationship between renal function, blood pressure variability (BPV), and nitric oxide (NO) in a group of African Americans with normal or mildly impaired renal function. 24-hour ambulatory blood pressure monitoring was performed, NO measured, and glomerular filtration rate (GFR) calculated in 38 African Americans. Participants were categorized as having normal (GFR > 90 mL/min per 1.73 m2) or mildly impaired (GFR 60–89 mL/min per 1.73 m2) renal function. Diastolic BPV was significantly lower in the mildly impaired renal function group. Regression analyses revealed a significant positive association between GFR and diastolic BPV for the entire study group. Plasma NO levels were significantly higher in the mildly impaired renal function group and negatively correlated with diastolic BPV. In conclusion, diastolic BPV was reduced in African Americans with mildly impaired renal function, which may be the result of increased NO production. These results conflict with previous findings in diseased and nonblack populations and could provide rationale for studying BPV early in the disease state when BP-buffering mechanisms are still preserved

Effects of Moderate Aerobic Exercise Training on Vascular Health and Blood Pressure in African Americans

As healthcare progresses toward individualized medicine, understanding how different racial groups respond to lifestyle interventions is valuable. It is established that African Americans have disproportionate levels of cardiovascular disease and impaired vascular health, and clinical practice guidelines suggest lifestyle interventions as the first line of treatment. Recently, the authors reported that 6 months of aerobic exercise improved inflammatory markers, flow-mediated dilation (FMD), and levels of circulating endothelial microparticles (EMPs) in African American adults. This study is a subgroup analysis of the aerobic exercise–induced changes in vascular health and blood pressure (BP) measures, including carotid artery intima-media thickness (IMT), nitroglycerin-mediated dilation (NMD), ambulatory BP, and office BP. Sedentary African American adults (53.4±6.2 years; 21 women and 5 men) showed improved vascular health but no change in BP. Carotid artery IMT decreased 6.4%, plasma nitric oxide levels increased 76.6%, plasma EMP levels decreased, percentage of FMD increased 59.6%, and FMD/NMD ratio increased 36.2% (P<.05 for all). Six months of aerobic exercise training is sufficient to elicit improvements in vascular structure and function in African Americans, even without improvements in BP measures or NMD (ie, smooth muscle function). To our knowledge, this is the first study to report such findings in African Americans

Effects of Moderate Aerobic Exercise Training on Vascular Health and Blood Pressure in African Americans

As healthcare progresses toward individualized medicine, understanding how different racial groups respond to lifestyle interventions is valuable. It is established that African Americans have disproportionate levels of cardiovascular disease and impaired vascular health, and clinical practice guidelines suggest lifestyle interventions as the first line of treatment. Recently, the authors reported that 6 months of aerobic exercise improved inflammatory markers, flow-mediated dilation (FMD), and levels of circulating endothelial microparticles (EMPs) in African American adults. This study is a subgroup analysis of the aerobic exercise–induced changes in vascular health and blood pressure (BP) measures, including carotid artery intima-media thickness (IMT), nitroglycerin-mediated dilation (NMD), ambulatory BP, and office BP. Sedentary African American adults (53.4±6.2 years; 21 women and 5 men) showed improved vascular health but no change in BP. Carotid artery IMT decreased 6.4%, plasma nitric oxide levels increased 76.6%, plasma EMP levels decreased, percentage of FMD increased 59.6%, and FMD/NMD ratio increased 36.2% (P<.05 for all). Six months of aerobic exercise training is sufficient to elicit improvements in vascular structure and function in African Americans, even without improvements in BP measures or NMD (ie, smooth muscle function). To our knowledge, this is the first study to report such findings in African Americans

Endothelial Activation Microparticles and Inflammation Status Improve with Exercise Training in African Americans

African Americans have the highest prevalence of hypertension in the world which may emanate from their predisposition to heightened endothelial inflammation. The purpose of this study was to determine the effects of a 6-month aerobic exercise training (AEXT) intervention on the inflammatory biomarkers interleukin-10 (IL-10), interleukin-6 (IL-6), and endothelial microparticle (EMP) CD62E+ and endothelial function assessed by flow-mediated dilation (FMD) in African Americans. A secondary purpose was to evaluate whether changes in IL-10, IL-6, or CD62E+ EMPs predicted the change in FMD following the 6-month AEXT intervention. A pre-post design was employed with baseline evaluation including office blood pressure, FMD, fasting blood sampling, and graded exercise testing. Participants engaged in 6 months of AEXT. Following the AEXT intervention, all baseline tests were repeated. FMD significantly increased, CD62E+ EMPs and IL-6 significantly decreased, and IL-10 increased but not significantly following AEXT. Changes in inflammatory biomarkers did not significantly predict the change in FMD. The change in significantly predicted the change in IL-10. Based on these results, AEXT may be a viable, nonpharmacological method to improve inflammation status and endothelial function and thereby contribute to risk reduction for cardiovascular disease in African Americans

Reviewing research evidence and the case of participation in sport and physical recreation by black and minority ethnic communities

The paper addresses the implications of using the process of systematic review in the many areas of leisure where there is a dearth of material that would be admitted into conventional Cochrane Reviews. This raises important questions about what constitutes legitimate knowledge, questions that are of critical import not just to leisure scholars, but to the formulation of policy. The search for certainty in an area that lacks conceptual consensus results in an epistemological imperialism that takes a geocentric form. While clearly, there is a need for good research design whatever the style of research, we contend that the wholesale rejection of insightful research is profligate and foolhardy. A mechanism has to be found to capitalise on good quality research of whatever form. In that search, we draw upon our experience of conducting a review of the material available on participation in sport and physical recreation by people from Black and minority ethnic groups. The paper concludes with a proposal for a more productive review process that makes better use of the full panoply of good quality research available. © 2012 © 2012 Taylor & Francis

Cmr1/WDR76 defines a nuclear genotoxic stress body linking genome integrity and protein quality control

DNA replication stress is a source of genomic instability. Here we identify ​changed mutation rate 1 (​Cmr1) as a factor involved in the response to DNA replication stress in Saccharomyces cerevisiae and show that ​Cmr1—together with ​Mrc1/​Claspin, ​Pph3, the chaperonin containing ​TCP1 (CCT) and 25 other proteins—define a novel intranuclear quality control compartment (INQ) that sequesters misfolded, ubiquitylated and sumoylated proteins in response to genotoxic stress. The diversity of proteins that localize to INQ indicates that other biological processes such as cell cycle progression, chromatin and mitotic spindle organization may also be regulated through INQ. Similar to ​Cmr1, its human orthologue ​WDR76 responds to proteasome inhibition and DNA damage by relocalizing to nuclear foci and physically associating with CCT, suggesting an evolutionarily conserved biological function. We propose that ​Cmr1/​WDR76 plays a role in the recovery from genotoxic stress through regulation of the turnover of sumoylated and phosphorylated proteins

Tracheal Replacement Therapy with a Stem Cell-Seeded Graft: Lessons from Compassionate Use Application of a GMP-Compliant Tissue-Engineered Medicine

Tracheal replacement for the treatment of end-stage airway disease remains an elusive goal. The use of tissue-engineered tracheae in compassionate use cases suggests that such an approach is a viable option. Here, a stem cell-seeded, decellularized tissue-engineered tracheal graft was used on a compassionate basis for a girl with critical tracheal stenosis after conventional reconstructive techniques failed. The graft represents the first cell-seeded tracheal graft manufactured to full good manufacturing practice (GMP) standards. We report important preclinical and clinical data from the case, which ended in the death of the recipient. Early results were encouraging, but an acute event, hypothesized to be an intrathoracic bleed, caused sudden airway obstruction 3 weeks post-transplantation, resulting in her death. We detail the clinical events and identify areas of priority to improve future grafts. In particular, we advocate the use of stents during the first few months post-implantation. The negative outcome of this case highlights the inherent difficulties in clinical translation where preclinical in vivo models cannot replicate complex clinical scenarios that are encountered. The practical difficulties in delivering GMP grafts underscore the need to refine protocols for phase I clinical trials

Preferential regulation of stably expressed genes in the human genome suggests a widespread expression buffering role of microRNAs

In this study, we comprehensively explored the stably expressed genes (SE genes) and fluctuant genes (FL genes) in the human genome by a meta-analysis of large scale microarray data. We found that these genes have distinct function distributions. miRNA targets are shown to be significantly enriched in SE genes by using propensity analysis of miRNA regulation, supporting the hypothesis that miRNAs can buffer whole genome expression fluctuation. The expression-buffering effect of miRNA is independent of the target site number within the 3'-untranslated region. In addition, we found that gene expression fluctuation is positively correlated with the number of transcription factor binding sites in the promoter region, which suggests that coordination between transcription factors and miRNAs leads to balanced responses to external perturbations

Bodies on the margins: regulating bodies, regulatory bodies

Sport is all about bodies, but some bodies are seen as on the margins and policies are directed at re-situating them into the mainstream. This article explores some of the ways in which embodied selves are the target of diversity policies and practices, especially those implemented by fan-based, anti-racist organisations. I use the phenomenological concepts of lived bodies and embodied selves to explore some of the processes involved in addressing 'bodies on the margins' in sport. Sport has long been considered a site for the creation of healthy citizens, a tradition which has been rearticulated to encompass diverse groups of people who are seen as under-represented in sport. This article looks at which embodied selves are encouraged to participate by non-governmental regulatory bodies in sport, to investigate the tension between the positive and negative dimensions of diversity politics in sport, as an example of what Paul Gilroy calls 'conviviality'

Survival and Growth of Yeast without Telomere Capping by Cdc13 in the Absence of Sgs1, Exo1, and Rad9

Maintenance of telomere capping is absolutely essential to the survival of eukaryotic cells. Telomere capping proteins, such as Cdc13 and POT1, are essential for the viability of budding yeast and mammalian cells, respectively. Here we identify, for the first time, three genetic modifications that allow budding yeast cells to survive without telomere capping by Cdc13. We found that simultaneous inactivation of Sgs1, Exo1, and Rad9, three DNA damage response (DDR) proteins, is sufficient to allow cell division in the absence of Cdc13. Quantitative amplification of ssDNA (QAOS) was used to show that the RecQ helicase Sgs1 plays an important role in the resection of uncapped telomeres, especially in the absence of checkpoint protein Rad9. Strikingly, simultaneous deletion of SGS1 and the nuclease EXO1, further reduces resection at uncapped telomeres and together with deletion of RAD9 permits cell survival without CDC13. Pulsed-field gel electrophoresis studies show that cdc13-1 rad9Δ sgs1Δ exo1Δ strains can maintain linear chromosomes despite the absence of telomere capping by Cdc13. However, with continued passage, the telomeres of such strains eventually become short and are maintained by recombination-based mechanisms. Remarkably, cdc13Δ rad9Δ sgs1Δ exo1Δ strains, lacking any Cdc13 gene product, are viable and can grow indefinitely. Our work has uncovered a critical role for RecQ helicases in limiting the division of cells with uncapped telomeres, and this may provide one explanation for increased tumorigenesis in human diseases associated with mutations of RecQ helicases. Our results reveal the plasticity of the telomere cap and indicate that the essential role of telomere capping is to counteract specific aspects of the DDR