Browsing Harvard Medical School by Title
Now showing items 4568-4587 of 18442
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Discovery and Characterization of a Disulfide-Locked C2-Symmetric Defensin Peptide
(American Chemical Society, 2014)We report the discovery of HD5-CD, an unprecedented C2-symmetric β-barrel-like covalent dimer of the cysteine-rich host-defense peptide human defensin 5 (HD5). Dimerization results from intermonomer disulfide exchange ... -
Discovery and Fine-Mapping of Glycaemic and Obesity-Related Trait Loci Using High-Density Imputation
(Public Library of Science, 2015)Reference panels from the 1000 Genomes (1000G) Project Consortium provide near complete coverage of common and low-frequency genetic variation with minor allele frequency ≥0.5% across European ancestry populations. Within ... -
Discovery and Functional Annotation of SIX6 Variants in Primary Open-Angle Glaucoma
(Public Library of Science, 2014)Glaucoma is a leading cause of blindness worldwide. Primary open-angle glaucoma (POAG) is the most common subtype and is a complex trait with multigenic inheritance. Genome-wide association studies have previously identified ... -
Discovery and genotyping of genome structural polymorphism by sequencing on a population scale
(2016)Accurate and complete analysis of genome variation in large populations will be required to understand the role of genome variation in complex disease. We present an analytical framework for characterizing genome deletion ... -
Discovery and Refinement of Loci Associated with Lipid Levels
(2013)Low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, and total cholesterol are heritable, modifiable, risk factors for coronary artery disease. To identify new loci and ... -
Discovery and replication of a peripheral tissue DNA methylation biosignature to augment a suicide prediction model
(BioMed Central, 2016)Background: Suicide is the second leading cause of death among adolescents in the USA, and rates are rising. Methods to identify individuals at risk are essential for implementing prevention strategies, and the development ... -
Discovery and saturation analysis of cancer genes across 21 tumor types
(2014)Summary While a few cancer genes are mutated in a high proportion of tumors of a given type (>20%), most are mutated at intermediate frequencies (2–20%). To explore the feasibility of creating a comprehensive catalog of ... -
Discovery and validation of sub-threshold genome-wide association study loci using epigenomic signatures
(eLife Sciences Publications, Ltd, 2016)Genetic variants identified by genome-wide association studies explain only a modest proportion of heritability, suggesting that meaningful associations lie 'hidden' below current thresholds. Here, we integrate information ... -
Discovery of 1,3-Diaminobenzenes as Selective Inhibitors of Platelet Activation at the PAR1 Receptor
(American Chemical Society, 2012)A high-throughput screen of the NIH-MLSMR compound collection, along with a series of secondary assays to identify potential targets of hit compounds, previously identified a 1,3-diaminobenzene scaffold that targets ... -
Discovery of 3,5-Diamino-1,2,4-triazole Ureas as Potent Anaplastic Lymphoma Kinase Inhibitors
(American Chemical Society, 2011)A series of novel 3,5-diamino-1,2,4-triazole benzyl ureas was identified as having potent anaplastic lymphoma kinase (ALK) inhibition exemplified by 15a, 20a, and 23a, which exhibited antiproliferative IC50 values of 70, ... -
Discovery of 3-Formyl-Tyrosine Metabolites from Pseudoalteromonas tunicata through Heterologous Expression
(American Chemical Society, 2009)Genome mining and identification of natural product gene clusters typically relies on the presence of canonical nonribosomal polypeptide synthetase (NRPS) or polyketide synthase (PKS) domains. Recently, other condensation ... -
Discovery of a Novel Polymer for Human Pluripotent Stem Cell Expansion and Multilineage Differentiation
(John Wiley and Sons Inc., 2015)A scalable and cost‐effective synthetic polymer substrate that supports robust expansion and subsequent multilineage differentiation of human pluripotent stem cells (hPSCs) with defined commercial media is presented. This ... -
Discovery of a Potent and Selective DDR1 Receptor Tyrosine Kinase Inhibitor
(American Chemical Society, 2013)The DDR1 receptor tyrosine kinase is activated by matrix collagens and has been implicated in numerous cellular functions such as proliferation, differentiation, adhesion, migration, and invasion. Here we report the discovery ... -
Discovery of a Potent, Covalent BTK Inhibitor for B-Cell Lymphoma
(American Chemical Society, 2014)BTK is a member of the TEC family of non-receptor tyrosine kinases whose deregulation has been implicated in a variety of B-cell-related diseases. We have used structure-based drug design in conjunction with kinome profiling ... -
Discovery of a Small-Molecule Probe for V-ATPase Function
(American Chemical Society, 2015)Lysosomes perform a critical cellular function as a site of degradation for diverse cargoes including proteins, organelles, and pathogens delivered through distinct pathways, and defects in lysosomal function have been ... -
Discovery of bioactive microbial gene products in inflammatory bowel disease
(Springer Science and Business Media LLC, 2022-05-25)Microbial communities and their associated bioactive compounds are often disrupted in conditions such as the inflammatory bowel diseases (IBD). However, even in well-characterized environments (e.g. the human gastrointestinal ... -
Discovery of Catalytically Active Orthologues of the Parkinson's Disease Kinase PINK1: Analysis of Substrate Specificity and Impact of Mutations
(The Royal Society, 2011)Missense mutations of the phosphatase and tensin homolog (PTEN)-induced kinase 1 (PINK1) gene cause autosomal-recessive Parkinson's disease. To date, little is known about the intrinsic catalytic properties of PINK1 since ... -
Discovery of CD8+ T cell epitopes in Chlamydia trachomatis infection through use of caged class I MHC tetramers
(National Academy of Sciences, 2008)Class I MHC tetramers allow direct phenotypic identification of CD8(+) T cell populations, but their production remains laborious. A peptide exchange strategy that employs class I MHC products loaded with conditional ligands ... -
Discovery of Dual-Action Membrane-Anchored Modulators of Incretin Receptors
(Public Library of Science, 2011)Background: The glucose-dependent insulinotropic polypeptide (GIP) and the glucagon-like peptide-1 (GLP-1) receptors are considered complementary therapeutic targets for type 2 diabetes. Using recombinant membrane-tethered ... -
Discovery of Genes Essential for Heme Biosynthesis through Large-Scale Gene Expression Analysis
(Elsevier BV, 2009)Heme biosynthesis consists of a series of eight enzymatic reactions that originate in mitochondria and continue in the cytosol before returning to mitochondria. Although these core enzymes are well studied, additional ...