18 research outputs found
Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function.
Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways
An identification key for eggs and egg sacs of spiders of potential agroeconomic importance: a feasibility study
Volume: 41Start Page: 176End Page: 18
An identification key for eggs and egg sacs of spiders of potential agroeconomic importance: a feasibility study
Stress factors associated with forest decline in xeric oak forests of south-central United States
A crossānational comparison of transparency signaling in corporate social responsibility reporting: The United States, South Korea, and China cases
DNA methylation arrays as surrogate measures of cell mixture distribution
<p>Abstract</p> <p>Background</p> <p>There has been a long-standing need in biomedical research for a method that quantifies the normally mixed composition of leukocytes beyond what is possible by simple histological or flow cytometric assessments. The latter is restricted by the labile nature of protein epitopes, requirements for cell processing, and timely cell analysis. In a diverse array of diseases and following numerous immune-toxic exposures, leukocyte composition will critically inform the underlying immuno-biology to most chronic medical conditions. Emerging research demonstrates that DNA methylation is responsible for cellular differentiation, and when measured in whole peripheral blood, serves to distinguish cancer cases from controls.</p> <p>Results</p> <p>Here we present a method, similar to regression calibration, for inferring changes in the distribution of white blood cells between different subpopulations (e.g. cases and controls) using DNA methylation signatures, in combination with a previously obtained external validation set consisting of signatures from purified leukocyte samples. We validate the fundamental idea in a cell mixture reconstruction experiment, then demonstrate our method on DNA methylation data sets from several studies, including data from a Head and Neck Squamous Cell Carcinoma (HNSCC) study and an ovarian cancer study. Our method produces results consistent with prior biological findings, thereby validating the approach.</p> <p>Conclusions</p> <p>Our method, in combination with an appropriate external validation set, promises new opportunities for large-scale immunological studies of both disease states and noxious exposures.</p
Inhibition of Hippocampal Ī²-Adrenergic Receptors Impairs Retrieval But Not Reconsolidation of Cocaine-Associated Memory and Prevents Subsequent Reinstatement
Treatment of Adrenocorticotropin-Dependent Cushingās Syndrome: A Consensus Statement
Objective: Our objective was to evaluate the published literature and reach a consensus on the treatment of patients with ACTH-dependent Cushingās syndrome, because there is no recent consensus on the management of this rare disorder