Effect of voluntary exercise on number and volume of cardiomyocytes and their mitochondria in the mouse left ventricle

Voluntary exercise (VE) has a beneficial influence on the heart and mean lifespan. The present study evaluates structural adaptations of cardiomyocytes and their mitochondria due to VE by new, unbiased stereological methods. Female, 7-9-week-old mice were randomly assigned to a control (CG, n=7) or VE group (EG, n=7). EG animals were housed in cages with free access to a running wheel and had a mean running distance of 6.7 (1.8)km per day. After 4weeks, the hearts of all mice were processed for light and electron microscopy. We estimated the number and volume of cardiomyocytes by the disector method and the number and volume of mitochondria by estimation of the Euler number. In comparison to CG, VE did not have an effect on the myocardial volume of the left ventricle (CG: 93 (10), EG: 103 (17) (mm3)), the number of cardiomyocytes (CG: 2.81 (0.27), EG: 2.82 (0.43) (×106)) and their number-weighted mean volume. However, the composition of the cardiomyocytes changed due to VE. The total volume of mitochondria (CG: 21.8 (4.9), EG: 32.2 (4.3) (mm3), P<0.01) and the total number (CG: 3.76 (0.44), EG: 7.02 (1.13) (×1010), P<0.001) were significantly higher in EG than in CG. The mean number-weighted mitochondrial volume was smaller in EG than in CG (P<0.05). In summary, VE does not alter ventricular volume nor cardiomyocyte volume or number but the oxidative capacity of cardiomyocytes by an increased mitochondrial number and total volume in the left ventricle. These structural changes may participate in the beneficial effects of V

Control of Tungiasis through Intermittent Application of a Plant-Based Repellent: An Intervention Study in a Resource-Poor Community in Brazil

Tungiasis is a parasitic skin disease caused by the female sand flea Tunga penetrans. The disease is frequent in resource-poor communities in South America and sub-Saharan Africa and affects the poorest of the poor. Sand flea disease is associated with a considerable morbidity and may lead to tetanus in non-vaccinated individuals. The degree of morbidity depends on the intensity of infestation, i.e., the number of embedded sand fleas a person has. Since tungiasis is a zoonosis involving a host of animal reservoirs, and because an effective treatment is not at hand, in resource-poor settings elimination is not feasible. Preventing morbidity to develop is therefore the only means to protect exposed individuals from sand flea disease. Similar to other arthropods, sand fleas can be repelled before they penetrate into the skin. In this study we show that the intermittent application of a plant-based repellent, of which the major component is coconut oil, reduces the intensity of infestation dramatically during the whole transmission season and prevents tungiasis-associated morbidity from developing. The prevention can be performed at the household level by the affected individuals themselves with minimal input from the health sector

Polygenic prediction of educational attainment within and between families from genome-wide association analyses in 3 million individuals

We conduct a genome-wide association study (GWAS) of educational attainment (EA) in a sample of ~3 million individuals and identify 3,952 approximately uncorrelated genome-wide-significant single-nucleotide polymorphisms (SNPs). A genome-wide polygenic predictor, or polygenic index (PGI), explains 12-16% of EA variance and contributes to risk prediction for ten diseases. Direct effects (i.e., controlling for parental PGIs) explain roughly half the PGI's magnitude of association with EA and other phenotypes. The correlation between mate-pair PGIs is far too large to be consistent with phenotypic assortment alone, implying additional assortment on PGI-associated factors. In an additional GWAS of dominance deviations from the additive model, we identify no genome-wide-significant SNPs, and a separate X-chromosome additive GWAS identifies 57

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Genome-wide association study identifies 74 loci associated with educational attainment

Educational attainment is strongly influenced by social and other environmental factors, but genetic factors are estimated to account for at least 20% of the variation across individuals1. Here we report the results of a genome-wide association study (GWAS) for educational attainment that extends our earlier discovery sample1,2 of 101,069 individuals to 293,723 individuals, and a replication study in an independent sample of 111,349 individuals from the UK Biobank. We identify 74 genome-wide significant loci associated with the number of years of schooling completed. Single-nucleotide polymorphisms associated with educational attainment are disproportionately found in genomic regions regulating gene expression in the fetal brain. Candidate genes are preferentially expressed in neural tissue, especially during the prenatal period, and enriched for biological pathways involved in neural development. Our findings demonstrate that, even for a behavioural phenotype that is mostly environmentally determined, a well-powered GWAS identifies replicable associated genetic variants that suggest biologically relevant pathways. Because educational attainment is measured in large numbers of individuals, it will continue to be useful as a proxy phenotype in efforts to characterize the genetic influences of related phenotypes, including cognition and neuropsychiatric diseases

Improvements in heap leaching to recover silver and gold from low-grade resources /

Includes bibliographical references.Mode of access: Internet

Hydrogen chloride sparging crystallization of aluminum chloride hexahydrate /

Bibliography: p. 15.Mode of access: Internet

Leaching gold-silver ores with sodium cyanide and thiourea under comparable conditions /

Bibliography: p. 6-7.Mode of access: Internet

A strong acid-weak acid method for producing aluminum chloride hexahydrate from kaolinitic clay /

Bibliography: p. 7.Mode of access: Internet

Aluminum extraction from anorthosite by leaching with hydrochloric acid and fluoride /

Bibliography: p. 7.Mode of access: Internet