Modeling the Influence of Vitamin D Deficiency on Cigarette Smoke-Induced Emphysema

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide. While the primary risk factor for COPD is cigarette smoke exposure, vitamin D deficiency has been epidemiologically implicated as a factor in the progressive development of COPD-associated emphysema. Because of difficulties inherent to studies involving multiple risk factors in the progression of COPD in humans, we developed a murine model in which to study the separate and combined effects of vitamin D deficiency and cigarette smoke exposure. During a 16-week period, mice were exposed to one of four conditions, control diet breathing room air (CD-NS), control diet with cigarette smoke exposure (CD-CSE), vitamin D deficient diet breathing room air (VDD-NS) or vitamin D deficient diet with cigarette smoke exposure (VDD-CSE). At the end of the exposure period, the lungs were examined by a pathologist and separately by morphometric analysis. In parallel experiments, mice were anesthetized for pulmonary function testing followed by sacrifice and analysis. Emphysema (determined by an increase in alveolar mean linear intercept length) was more severe in the VDD-CSE mice compared to control animals and animals exposed to VDD or CSE alone. The VDD-CSE and the CD-CSE mice had increased total lung capacity and increased static lung compliance. There was also a significant increase in the matrix metalloproteinase-9: tissue inhibitor of metalloproteinases-1 (TIMP-1) ratio in VDD-CSE mice compared with all controls. Alpha-1 antitrypsin (A1AT) expression was reduced in VDD-CSE mice as well. In summary, vitamin D deficiency, when combined with cigarette smoke exposure, seemed to accelerate the appearance of emphysemas, perhaps by virtue of an increased protease-antiprotease ratio in the combined VDD-CSE animals. These results support the value of our mouse model in the study of COPD

Exposure and fetal growth-associated miRNA alterations in the human placenta

Researchers have begun to examine epigenetic alterations in the placenta, making key advances in understanding the epigenetic regulatory mechanisms of the placenta that define underlying processes of human development and disease. Examining changes in microRNA (miRNA) expression associated with environmental exposures and fetal growth is providing critical insights into the biology of development, response to in utero exposure, and future disease risk assessment. This review aims to highlight previous studies describing changes in miRNA expression in the human placenta associated with in utero exposure and fetal growth and seeks to assess the future directions in this exciting field of research

‘Race’ Talk! Tensions and Contradictions in Sport and PE

Background: The universal sport discourses of inclusion, belonging, meritocracy, agency, and equality are so widespread that few challenge them. It is clear from the most cursory interest in sport, PE and society that the lived reality is quite different and ambiguous. Racial disparities in the leadership and administration of sport are commonplace world wide; yet from research into ‘race’ in sport and PE the public awareness of these issues is widespread, where many know that racism takes place it is always elsewhere For many this racism is part of the game and something that enables an advantage to be stolen, for others it is trivial and not worthy of deeper thought. This paper explores the contradictions and tensions of the author’s experience of how sport and PE students talk about ‘race’. ‘Race’ talk is considered here in the context of passive everyday ‘race’ talk, dominant discourses in sporting cultures, and colour-blindness. This paper focuses on the pernicious yet persistent nature of ‘race’ talk while demystifying its multifarious, spurious, and more persuasive daily iterations. Theoretical framework: Drawing on Guinier and Torres’ (2003) ideas of resistance through political race consciousness and Bonilla-Silva’s (2010) notion of colour-blindness the semantics of ‘race’ and racialisation in sport and PE are interrogated through the prism of Critical Race Theory (CRT). Critical race scholarship has been used in sport and PE to articulate a political application of ‘race’ as a starting point for critical activism, to disrupt whiteness, and to explore the implications of ‘race’ and racism. CRT is used here to centre ‘race’ and racialised relations where disciplines have consciously or otherwise excluded them. Importantly, the centreing of ‘race’ by critical race scholars has advanced a strategic and pragmatic engagement with this slippery concept that recognises its paradoxical but symbolic location in social relations. Discussion: Before exploring ‘race’ talk in the classroom, using images from the sport media as a pedagogical tool, the paper considers how effortlessly ‘race’ is recreated and renewed. The paper then turns to explore how the effortless turn to everyday ‘race’ talk in the classroom can be viewed as an opportunity to disrupt common racialised assumptions with the potential to implicate those that passively engage in it. Further the diagnostic, aspirational and activist goals of political race consciousness are established as vehicles for a positive sociological experience in the classroom. Conclusion: The work concludes with a pragmatic consideration of the uses and dangers of passive everyday ‘race’ talk and the value of a political race consciousness in sport and PE. Part of the explanation for the perpetuation of ‘race’ talk and the relative lack of concern with its impact in education and wider society is focused on how the sovereignty of sport and PE trumps wider social concerns of ‘race’ and racism because of at least four factors 1) the liberal left discourses of sporting utopianism 2) the ‘race’ logic that pervades sport, based upon the perceived equal access and fairness of sport as it coalesces with the, 3) 'incontrovertible facts' of black and white superiority [and inferiority] in certain sports, ergo the racial justifications for patterns of activity in sport and PE 4) the racist logic of the Right perpetuated through a biological reductionism in sport and PE discourses. Keywords: ‘Race’ Talk; Critical Race Theory; Political Race Consciousnes

Genetic Ancestry, Social Classification, and Racial Inequalities in Blood Pressure in Southeastern Puerto Rico

The role of race in human genetics and biomedical research is among the most contested issues in science. Much debate centers on the relative importance of genetic versus sociocultural factors in explaining racial inequalities in health. However, few studies integrate genetic and sociocultural data to test competing explanations directly.We draw on ethnographic, epidemiologic, and genetic data collected in Southeastern Puerto Rico to isolate two distinct variables for which race is often used as a proxy: genetic ancestry versus social classification. We show that color, an aspect of social classification based on the culturally defined meaning of race in Puerto Rico, better predicts blood pressure than does a genetic-based estimate of continental ancestry. We also find that incorporating sociocultural variables reveals a new and significant association between a candidate gene polymorphism for hypertension (alpha(2C) adrenergic receptor deletion) and blood pressure.This study addresses the recognized need to measure both genetic and sociocultural factors in research on racial inequalities in health. Our preliminary results provide the most direct evidence to date that previously reported associations between genetic ancestry and health may be attributable to sociocultural factors related to race and racism, rather than to functional genetic differences between racially defined groups. Our results also imply that including sociocultural variables in future research may improve our ability to detect significant allele-phenotype associations. Thus, measuring sociocultural factors related to race may both empower future genetic association studies and help to clarify the biological consequences of social inequalities

Cigarette Smoke Extract (CSE) Delays NOD2 Expression and Affects NOD2/RIPK2 Interactions in Intestinal Epithelial Cells

Genetic and environmental factors influence susceptibility to Crohn's disease (CD): NOD2 is the strongest individual genetic determinant and smoking the best-characterised environmental factor. Carriage of NOD2 mutations predispose to small-intestinal, stricturing CD, a phenotype also associated with smoking. We hypothesised that cigarette smoke extract (CSE) altered NOD2 expression and function in intestinal epithelial cells.Intestinal epithelial cell-lines (SW480, HT29, HCT116) were stimulated with CSE and nicotine (to mimic smoking) ±TNFα (to mimic inflammation). NOD2 expression was measured by qRT-PCR and western blotting; NOD2-RIPK2 interactions by co-immunoprecipitation (CoIP); nuclear NFκB-p65 by ELISA; NFκB activity by luciferase reporter assays and chemokines (CCL20, IL8) in culture supernatants by ELISA. In SW480 and HT29 cells the TNFα-induced NOD2 expression at 4 hours was reduced by CSE (p = 0.0226), a response that was dose-dependent (p = 0.003) and time-dependent (p = 0.0004). Similar effects of CSE on NOD2 expression were seen in cultured ileal biopsies from healthy individuals. In SW480 cells CSE reduced TNFα-induced NFκB-p65 translocation at 15 minutes post-stimulation, upstream of NOD2. Levels of the NOD2-RIPK2 complex were no different at 8 hours post-stimulation with combinations of CSE, nicotine and TNFα, but at 18 hours it was increased in cells stimulated with TNFα+CSE but decreased with TNFα alone (p = 0.0330); CSE reduced TNFα-induced NFκB activity (p = 0.0014) at the same time-point. At 24 hours, basal CCL20 and IL8 (p<0.001 for both) and TNFα-induced CCL20 (p = 0.0330) production were decreased by CSE. CSE also reduced NOD2 expression, CCL20 and IL8 production seen with MDP-stimulation of SW480 cells pre-treated with combinations of TNFα and CSE.CSE delayed TNFα-induced NOD2 mRNA expression and was associated with abnormal NOD2/RIPK2 interaction, reduced NFκB activity and decreased chemokine production. These effects may be involved in the pathogenesis of small-intestinal CD and may have wider implications for the effects of smoking in NOD2-mediated responses

La semántica fugitiva: "raza, color y vida cotidiana en Puerto Rico.

Resumen en inglés.Resumen en español

Racismo en Puerto Rico: Surveying perceptions of racism

This study engaged the relatively new method of on-line survey methodology to address a few key questions about perceptions of racism in Puerto Rico. The questions addressed whether Puerto Ricans perceive anti-black racism to exist; whether they have experienced it personally, or observed racist behaviors and practices; and in what realms of social life they perceive racism to exist. The article correlates these findings with the way respondents described themselves racially. Thus, this article reports on three distinct areas: (1) the use of on-line survey methodology to address questions of race and racism; (2) quantitative response patterns about racism in PR and among Puerto Ricans and their relationship to how people selfdescribed racially; and (3) to how, when, and where racism is manifested according to respondents

Modeling the influence of vitamin D deficiency on cigarette smoke-induced emphysema.

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide. While the primary risk factor for COPD is cigarette smoke exposure, vitamin D deficiency has been epidemiologically implicated as a factor in the progressive development of COPD-associated emphysema. Because of difficulties inherent to studies involving multiple risk factors in the progression of COPD in humans, we developed a murine model in which to study the separate and combined effects of vitamin D deficiency and cigarette smoke exposure. During a 16 week period, mice were exposed to one of four conditions, control diet breathing room air (CD-NS), control diet with cigarette smoke exposure (CD-CSE), vitamin D deficient diet breathing room air (VDD-NS) or vitamin D deficient diet with cigarette smoke exposure (VDD-CSE). At the end of the exposure period, the lungs were examined by a pathologist and separately by morphometric analysis. In parallel experiments, mice were anesthetized for pulmonary function testing followed by sacrifice and analysis. Emphysema (determined by an increase in alveolar mean linear intercept length) was more severe in the VDD-CSE mice compared to control animals and animals exposed to VDD or CSE alone. The VDD-CSE and the CD-CSE mice had increased total lung capacity and increased static lung compliance. There was also a significant increase in the matrix metalloproteinase-9: tissue inhibitor of metalloproteinases-1 ratio in VDD-CSE mice compared with all controls. Alpha-1 antitrypsin expression was reduced in VDD-CSE mice as well. In summary, vitamin D deficiency, when combined with cigarette smoke exposure, seemed to accelerate the appearance of emphysemas, perhaps by virtue of an increased protease-antiprotease ratio in the combined VDD-CSE animals. These results support the value of our mouse model in the study of COPD