101 research outputs found

    Prediction of cis-regulatory elements controlling genes differentially expressed by retinal and choroidal vascular endothelial cells

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    Cultured endothelial cells of the human retina and choroid demonstrate distinct patterns of gene expression. We hypothesized that differential gene expression reflected differences in the interactions of transcription factors and respective cis-regulatory motifs(s) in these two endothelial cell subpopulations, recognizing that motifs often exist as modules. We tested this hypothesis in silico by using TRANSFAC Professional and CisModule to identify cis-regulatory motifs and modules in genes that were differentially expressed by human retinal versus choroidal endothelial cells, as identified by analysis of a microarray data set. Motifs corresponding to eight transcription factors were significantly (p < 0.05) differentially abundant in genes that were relatively highly expressed in retinal (i.e., glucocorticoid receptor, high mobility group AT-hook 1, heat shock transcription factor 1, p53, vitamin D receptor) or choroidal (i.e., transcription factor E2F, Yin Yang 1, zinc finger 5) endothelial cells. Predicted cis-regulatory modules were quite different for these two groups of genes. Our findings raise the possibility of exploiting specific cis-regulatory motifs to target therapy at the ocular endothelial cells subtypes responsible for neovascular age-related macular degeneration or proliferative diabetic retinopathy

    Who wants a slimmer body? The relationship between body weight status, education level and body shape dissatisfaction among young adults in Hong Kong

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    Background: Body shape dissatisfaction has been thought to have an indispensable impact on weight control behaviors. We investigated the prevalence of body shape dissatisfaction (BSD) and explored its association with weight status, education level and other determinants among young adults in Hong Kong. Methods. Information on anthropometry, BSD, and socio-demographics was collected from a random sample of 1205 young adults (611 men and 594 women) aged 18-27 in a community-based household survey. BSD was defined as a discrepancy between current and ideal body shape based on a figure rating scale. Cross-tabulations, homogeneity tests and logistic regression models were applied. Results: The percentages of underweight men and women were 16.5% and 34.9% respectively, and the corresponding percentages of being overweight or obese were 26.7% and 13.2% for men and women respectively. Three-quarters of young adults had BSD. Among women, 30.9% of those underweight and 75.5% of those with normal weight desired a slimmer body shape. Overweight men and underweight women with lower education level were more likely to have a mismatch between weight status and BSD than those with higher education level. After controlling for other determinants, underweight women were found to have a higher likelihood to maintain their current body shapes than other women. Men were found to be less likely to have a mismatch between weight status and BSD than women. Conclusions: Overweight and obesity in men and underweight in women were prevalent among Hong Kong young adults. Inappropriate body shape desire might predispose individuals to unhealthy weight loss or gain behaviors. Careful consideration of actual weight status in body shape desire is needed in health promotion and education, especially for underweight and normal weight women and those with a low education level. © 2011 Cheung et al; licensee BioMed Central Ltd.published_or_final_versio

    The dopamine β-hydroxylase -1021C/T polymorphism is associated with the risk of Alzheimer's disease in the Epistasis Project

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    Contains fulltext : 88930.pdf (publisher's version ) (Open Access)BACKGROUND: The loss of noradrenergic neurones of the locus coeruleus is a major feature of Alzheimer's disease (AD). Dopamine beta-hydroxylase (DBH) catalyses the conversion of dopamine to noradrenaline. Interactions have been reported between the low-activity -1021T allele (rs1611115) of DBH and polymorphisms of the pro-inflammatory cytokine genes, IL1A and IL6, contributing to the risk of AD. We therefore examined the associations with AD of the DBH -1021T allele and of the above interactions in the Epistasis Project, with 1757 cases of AD and 6294 elderly controls. METHODS: We genotyped eight single nucleotide polymorphisms (SNPs) in the three genes, DBH, IL1A and IL6. We used logistic regression models and synergy factor analysis to examine potential interactions and associations with AD. RESULTS: We found that the presence of the -1021T allele was associated with AD: odds ratio = 1.2 (95% confidence interval: 1.06-1.4, p = 0.005). This association was nearly restricted to men < 75 years old: odds ratio = 2.2 (1.4-3.3, 0.0004). We also found an interaction between the presence of DBH -1021T and the -889TT genotype (rs1800587) of IL1A: synergy factor = 1.9 (1.2-3.1, 0.005). All these results were consistent between North Europe and North Spain. CONCLUSIONS: Extensive, previous evidence (reviewed here) indicates an important role for noradrenaline in the control of inflammation in the brain. Thus, the -1021T allele with presumed low activity may be associated with misregulation of inflammation, which could contribute to the onset of AD. We suggest that such misregulation is the predominant mechanism of the association we report here

    Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial

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    Aims  The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results  Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. Conclusion  After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.For complete list of authors see http://dx.doi.org/10.1093/eurheartj/ehz299</p

    Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

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    In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

    A 3,000-year-old Egyptian emmer wheat genome reveals dispersal and domestication history

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    Tetraploid emmer wheat (Triticum turgidum ssp. dicoccon) is a progenitor of the world’s most widely grown crop, hexaploid bread wheat (Triticum aestivum), as well as the direct ancestor of tetraploid durum wheat (T. turgidum subsp. turgidum). Emmer was one of the first cereals to be domesticated in the old world; it was cultivated from around 9700 BC in the Levant1,2 and subsequently in south-western Asia, northern Africa and Europe with the spread of Neolithic agriculture3,4. Here, we report a whole-genome sequence from a museum specimen of Egyptian emmer wheat chaff, 14C dated to the New Kingdom, 1130–1000 BC. Its genome shares haplotypes with modern domesticated emmer at loci that are associated with shattering, seed size and germination, as well as within other putative domestication loci, suggesting that these traits share a common origin before the introduction of emmer to Egypt. Its genome is otherwise unusual, carrying haplotypes that are absent from modern emmer. Genetic similarity with modern Arabian and Indian emmer landraces connects ancient Egyptian emmer with early south-eastern dispersals, whereas inferred gene flow with wild emmer from the Southern Levant signals a later connection. Our results show the importance of museum collections as sources of genetic data to uncover the history and diversity of ancient cereals

    G6PD deficiency in Latin America: systematic review on prevalence and variants

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    Plasmodium vivax radical cure requires the use of primaquine (PQ), a drug that induces haemolysis in glucose-6-phosphate dehydrogenase deficient (G6PDd) individuals, which further hampers malaria control efforts. The aim of this work was to study the G6PDd prevalence and variants in Latin America (LA) and the Caribbean region. A systematic search of the published literature was undertaken in August 2013. Bibliographies of manuscripts were also searched and additional references were identified. Low prevalence rates of G6PDd were documented in Argentina, Bolivia, Mexico, Peru and Uruguay, but studies from Curaçao, Ecuador, Jamaica, Saint Lucia, Suriname and Trinidad, as well as some surveys carried out in areas of Brazil, Colombia and Cuba, have shown a high prevalence (> 10%) of G6PDd. The G6PD A-202A mutation was the variant most broadly distributed across LA and was identified in 81.1% of the deficient individuals surveyed. G6PDd is a frequent phenomenon in LA, although certain Amerindian populations may not be affected, suggesting that PQ could be safely used in these specific populations. Population-wide use of PQ as part of malaria elimination strategies in LA cannot be supported unless a rapid, accurate and field-deployable G6PDd diagnostic test is made available
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