Genetic insights into resting heart rate and its role in cardiovascular disease.

Resting heart rate is associated with cardiovascular diseases and mortality in observational and Mendelian randomization studies. The aims of this study are to extend the number of resting heart rate associated genetic variants and to obtain further insights in resting heart rate biology and its clinical consequences. A genome-wide meta-analysis of 100 studies in up to 835,465 individuals reveals 493 independent genetic variants in 352 loci, including 68 genetic variants outside previously identified resting heart rate associated loci. We prioritize 670 genes and in silico annotations point to their enrichment in cardiomyocytes and provide insights in their ECG signature. Two-sample Mendelian randomization analyses indicate that higher genetically predicted resting heart rate increases risk of dilated cardiomyopathy, but decreases risk of developing atrial fibrillation, ischemic stroke, and cardio-embolic stroke. We do not find evidence for a linear or non-linear genetic association between resting heart rate and all-cause mortality in contrast to our previous Mendelian randomization study. Systematic alteration of key differences between the current and previous Mendelian randomization study indicates that the most likely cause of the discrepancy between these studies arises from false positive findings in previous one-sample MR analyses caused by weak-instrument bias at lower P-value thresholds. The results extend our understanding of resting heart rate biology and give additional insights in its role in cardiovascular disease development

Perfil eletroforético das proteínas séricas de frangos de corte alimentados com dietas contendo aflatoxinas e/ou argila clinoptilolita natural Electrophoresis profile of serum proteins in broilers fed with diets containing aflatoxins and/or natural clinoptilolite clay

O objetivo do presente trabalho foi avaliar o perfil eletroforético das proteínas séricas de frangos de corte alimentados com dietas contendo aflatoxinas e/ou argila clinoptilolita natural. Foram utilizados 528 frangos de corte, machos, da linhagem Ross, distribuídos em seis tratamentos com 4 repetições cada: T1 - testemunha (ração sem aflatoxinas ou clinoptilolita), T2 - ração com 5ppm de aflatoxinas, T3 - ração com 0,25% de clinoptilolita, T4 - ração com 5ppm de aflatoxinas e 0,25% de clinoptilolita, T5 - ração com 0,5% de clinoptilolita e T6 - ração com 5ppm de aflatoxinas e 0,5% de clinoptilolita. Os animais ficaram alojados em 24 boxes, e submetidos aos tratamentos do 1&deg; ao 42&deg; dia, quando foram sacrificados. Foram analisadas as proteínas totais, as frações albumina, alfa 1, alfa 2, beta e gama. Com exceção das médias da fração gama, o teste de Tukey revelou diferenças significativas (P<0,05) nas médias de todas as proteínas totais e frações protéicas nos tratamentos onde as aflatoxinas estavam presentes. A ação das aflatoxinas nas proteínas totais ocorre na síntese de albumina e globulinas (frações alfa e beta). As gamaglobulinas não são afetadas pelas aflatoxinas. Em relação ao controle, as aves alimentadas com dietas com aflatoxinas e clinoptilolita apresentaram baixos (P<0,05) níveis de proteína total, albumina e globulinas (alfa e beta). Conclui-se que as aflatoxinas alteram o perfil eletroforético e que a clinoptilolita adicionada na ração não é capaz de evitar essas alterações.<br>This study was aimed at evaluating the electrophoresis profile of serum protein in broilers fed with diets containing aflatoxins and natural clinoptilolite clay. Five hundred and twenty eight male broilers Ross were distributed in six treatments and each one with 4 replications: T1 - control (without aflatoxins or clinoptilolite), T2 -5ppm of aflatoxins, T3 -0.25% of clinoptilolite, T4 -5ppm of aflatoxins and 0.25% of clinoptilolite, T5 -0.5% of clinoptilolite and T6 - 5ppm of aflatoxins and 0.5% of clinoptilolite. The broilers were allocated in 24 boxes and submitted to a treatments for 42 days, when they were slaughtered. Total proteins, albumin fractions, alpha 1, alpha 2, beta and gamma were analyzed. Except gamma fraction the Tukey test showed differences (P<0.05) on serum total proteins and proteins fractions in all treatments which aflatoxin was present. The clinoptilolite did not modify (P<0.05) the serum proteins. The control broilers fed with diets containing aflatoxins and clinoptilolite presented low levels (P<0.05) of total protein, albumin, and globulins (alpha and beta fractions). In conclusion, aflatoxins change the electrophoresis profile and clinoptilolite is not able to protect avoid these changes

The consequences of disrupted dispersal in fragmented red-cockaded woodpecker Picoides borealis populations.

1. Habitat fragmentation may adversely affect animal populations through several mechanisms. However, little is known about how the impacts of some of these mechanisms are manifested in altered dynamics of wild populations. 2. We used a spatially explicit individual-based simulation model to examine the potential effects of disrupted dispersal due to fragmentation on the population dynamics of the endangered, co-operatively breeding, red-cockaded woodpecker Picoides borealis. 3. We simulated population dynamics as a function of population size and spatial aggregation of territories. Dispersal success (but not mortality or fecundity) was an emergent property of model runs. In the model all female and some male fledglings dispersed in straight lines in random directions, and the remaining males stayed on their natal territories as helpers and competed for breeding vacancies in their immediate neighbourhood. 4. Population trend was tied to the higher dispersal success of both males and females in larger and less fragmented populations. Helpers were more successful than dispersing males. Male breeder recruitment depended entirely on helpers when populations were small (25 or 100 territories). 5. Declining populations were characterized by high emigration rates and both failure and delay in female recruitment. The large numbers of unpaired males resulted in lowered reproductive output at the population level and in the loss of territories. Populations of 25 territories were stable when territories were highly aggregated, despite high emigration rates. These results closely match empirical observations. 6. A number of co-operatively breeding species are endangered. The unusual dispersal behaviour of helpers may make such species sensitive to habitat fragmentation but also resilient to reductions in population size when territories are aggregated. Small populations of co-operative breeders may have considerable conservation value as a source of genetic diversity

Meta-analysis identifies six new susceptibility loci for atrial fibrillation.

Atrial fibrillation is a highly prevalent arrhythmia and a major risk factor for stroke, heart failure and death(1). We conducted a genome-wide association study (GWAS) in individuals of European ancestry, including 6,707 with and 52,426 without atrial fibrillation. Six new atrial fibrillation susceptibility loci were identified and replicated in an additional sample of individuals of European ancestry, including 5,381 subjects with and 10,030 subjects without atrial fibrillation (P &lt; 5 x 10(-8)). Four of the loci identified in Europeans were further replicated in silico in a GWAS of Japanese individuals, including 843 individuals with and 3,350 individuals without atrial fibrillation. The identified loci implicate candidate genes that encode transcription factors related to cardiopulmonary development, cardiac-expressed ion channels and cell signaling molecules

DNA methylation signature of chronic low-grade inflammation and its role in cardio-respiratory diseases

Chronic inflammation, marked by C-reactive protein, has been associated with changes in methylation, but the causal relationship is unclear. Here, the authors perform a Epigenome-wide association meta-analysis for C-reactive protein levels and find that these methylation changes are likely the consequence of inflammation and could contribute to disease.We performed a multi-ethnic Epigenome Wide Association study on 22,774 individuals to describe the DNA methylation signature of chronic low-grade inflammation as measured by C-Reactive protein (CRP). We find 1,511 independent differentially methylated loci associated with CRP. These CpG sites show correlation structures across chromosomes, and are primarily situated in euchromatin, depleted in CpG islands. These genomic loci are predominantly situated in transcription factor binding sites and genomic enhancer regions. Mendelian randomization analysis suggests altered CpG methylation is a consequence of increased blood CRP levels. Mediation analysis reveals obesity and smoking as important underlying driving factors for changed CpG methylation. Finally, we find that an activated CpG signature significantly increases the risk for cardiometabolic diseases and COPD