Search results for "31"
showing 10 items of 4401 documents
Genetic and Environmental Effects on Telomere Length and Lung Function: A Twin Study.
2015
Background The purpose of the study was to estimate the heritability of leukocyte telomere length (LTL) and lung function and to examine whether LTL and lung function share genetic or environmental effects in common. Methods 386 monozygotic and dizygotic Finnish twin sisters (age 68.4±3.4 years) were included. Relative LTL was determined from peripheral blood DNA by qPCR. Lung function measures of FEV1, FVC, FEV1/FVC, and PEF were derived from spirometry. Genetic modeling was performed with MPlus statistical software. Results Univariate analysis revealed that in LTL, 62% (95% confidence interval 50-72) of the variance was explained by additive genetic and 38% (28-50) by unique environmental…
Variants associated with HHIP expression have sex-differential effects on lung function
2021
Background: Lung function is highly heritable and differs between the sexes throughout life. However, little is known about sex-differential genetic effects on lung function. We aimed to conduct the first genome-wide genotype-by-sex interaction study on lung function to identify genetic effects that differ between males and females. Methods: We tested for interactions between 7,745,864 variants and sex on spirometry-based measures of lung function in UK Biobank (N=303,612), and sought replication in 75,696 independent individuals from the SpiroMeta consortium. Results: Five independent single-nucleotide polymorphisms (SNPs) showed genome-wide significant (P<5x10-8) interactions with sex …
Assessing statistical significance in multivariable genome wide association analysis
2016
Motivation: Although Genome Wide Association Studies (GWAS) genotype a very large number of single nucleotide polymorphisms (SNPs), the data are often analyzed one SNP at a time. The low predictive power of single SNPs, coupled with the high significance threshold needed to correct for multiple testing, greatly decreases the power of GWAS. Results: We propose a procedure in which all the SNPs are analyzed in a multiple generalized linear model, and we show its use for extremely high-dimensional datasets. Our method yields P-values for assessing significance of single SNPs or groups of SNPs while controlling for all other SNPs and the family wise error rate (FWER). Thus, our method tests whe…
Additives for vaccine storage to improve thermal stability of adenoviruses from hours to months
2016
Up to 80% of the cost of vaccination programmes is due to the cold chain problem (that is, keeping vaccines cold). Inexpensive, biocompatible additives to slow down the degradation of virus particles would address the problem. Here we propose and characterize additives that, already at very low concentrations, improve the storage time of adenovirus type 5. Anionic gold nanoparticles (10−8–10−6 M) or polyethylene glycol (PEG, molecular weight ∼8,000 Da, 10−7–10−4 M) increase the half-life of a green fluorescent protein expressing adenovirus from ∼48 h to 21 days at 37 °C (from 7 to >30 days at room temperature). They replicate the known stabilizing effect of sucrose, but at several orders of…
American Trypanosomiasis Chagas disease : one hundred years of research
2017
Abstract In understanding biodiversity, taxonomy and systematics work together, although the two terms are often confused. The objective of systematics is to understand the natural mechanisms responsible for the biodiversity, while the task of taxonomy is to set up a useful classification of the organisms concerned. The Triatominae (Hemiptera, Reduviidae) are the vectors of Chagas disease. Their classification faces frequent divergence between the modern concepts of systematics and the traditional, morphologically-based, classification. This chapter revises the main concepts of species in general, and their application to the Triatominae. We summarize the current classification of the vecto…
Under pressure: phenotypic divergence and convergence associated with microhabitat adaptations in Triatominae
2021
AbstractBackgroundTriatomine bugs, the vectors of Chagas disease, associate with vertebrate hosts in highly diverse ecotopes. When these blood-sucking bugs adapt to new microhabitats, their phenotypes may change. Although understanding phenotypic variation is key to the study of adaptive evolution and central to phenotype-based taxonomy, the drivers of phenotypic change and diversity in triatomines remain poorly understood.Methods/FindingsWe combined a detailed phenotypic appraisal (including morphology and morphometrics) with mitochondrialcytband nuclear ITS2 DNA-sequence analyses to studyRhodnius ecuadoriensispopulations from across the species’ range. We found three major, naked-eye phen…
Biological Effect of a Hybrid Anticancer Agent Based on Kinase and Histone Deacetylase Inhibitors on Triple-Negative (MDA-MB231) Breast Cancer Cells
2016
We examined the effects of the histone deacetylase inhibitor (HDACi) suberoylanilide\ud hydroxamic acid (SAHA) combined with the vascular endothelial growth factor receptor-1/2 inhibitor\ud (3Z)-5-hydroxy-3-(1H-pyrrol-2-ylmethylidene)-2,3-dihydro-1H-indol-2-one on MDA-MB-231 breast\ud cancer cells (triple-negative) in the form of both a cocktail of the separate compounds and a chemically\ud synthesized hybrid (N-hydroxy-N'-[(3Z)-2-oxo-3-(1H-pyrrol-2-ylmethylidene)-2,3-dihydro-1H-indol-\ud 5-yl]octanediamide). Comparative flow cytometric and Western blot analyses were performed on\ud cocktail- and hybrid-treated cells to evaluate cell cycle distribution, autophagy/apoptosis modulation,\ud an…
Surge of Peripheral Arginine Vasopressin in a Rat Model of Birth Asphyxia
2018
Mammalian birth is accompanied by a period of obligatory asphyxia, which consists of hypoxia (drop in blood O2 levels) and hypercapnia (elevation of blood CO2 levels). Prolonged, complicated birth can extend the asphyxic period, leading to a pathophysiological situation, and in humans, to the diagnosis of clinical birth asphyxia, the main cause of hypoxic-ischemic encephalopathy (HIE). The neuroendocrine component of birth asphyxia, in particular the increase in circulating levels of arginine vasopressin (AVP), has been extensively studied in humans. Here we show for the first time that normal rat birth is also accompanied by an AVP surge, and that the fetal AVP surge is further enhanced in…
A widely used sampling device in colorectal cancer screening programmes allows for large-scale microbiome studies.
2018
We read with interest the article by Passamonti et al ,1 reporting the performance of two different faecal immunochemical tests (FITs) highlighting the importance of standardisation and validation of screening methodologies. Conventionally, laboratory-based FIT is the preferred approach in testing for occult blood in faeces, which includes colorectal cancer screening programmes.2–4 The potential of preserving stable faecal samples in a widely used FIT buffer for microbiome research would enable prospective microbiome studies in generally healthy subjects undergoing colorectal cancer screening. For this purpose, we evaluated faecal sample stability in the commonly used OC-Sensor (Eiken Chemi…
Seroprevalence of Toxoplasma gondii in domestic pigs, sheep, cattle, wild boars, and moose in the Nordic-Baltic region: A systematic review and meta-…
2019
Background: Toxoplasma gondii is an important foodborne zoonotic parasite. Meat of infected animals is presumed to constitute a major source of human infection and may be a driver of geographical variation in the prevalence of anti-T. gondii antibodies in humans, which is substantial in the Nordic-Baltic region in northern Europe. However, data on seroprevalence of T. gondii in different animal species used for human consumption are scattered. Methods: We conducted a systematic review of seroprevalence studies and meta-analysis to estimate the seroprevalence of T. gondii in five animal species that are raised or hunted for human consumption in the Nordic-Baltic region: domestic pigs (Sus sc…