A5101554309- Receptor Mechanisms and Signaling
- Neuropeptides and Animal Physiology
- Immune Response and Inflammation
- Bioinformatics and Genomic Networks
- Stress Responses and Cortisol
- Neuroscience and Neuropharmacology Research
- interferon and immune responses
- Computational Drug Discovery Methods
- Inflammasome and immune disorders
- Tryptophan and brain disorders
- CRISPR and Genetic Engineering
- Trace Elements in Health
- Cancer-related gene regulation
- Genetic Associations and Epidemiology
- Neuroinflammation and Neurodegeneration Mechanisms
- Peptidase Inhibition and Analysis
- Immunotherapy and Immune Responses
- Molecular Biology Techniques and Applications
- Photoreceptor and optogenetics research
- Genomics and Phylogenetic Studies
- Health Systems, Economic Evaluations, Quality of Life
- Sulfur Compounds in Biology
- Nicotinic Acetylcholine Receptors Study
- Primary Care and Health Outcomes
- Plant Micronutrient Interactions and Effects
National Center for Advancing Translational Sciences
2019-2025
National Institutes of Health
2023-2025
European Bioinformatics Institute
2015-2023
United States Army Medical Research Institute of Infectious Diseases
2016
GlaxoSmithKline (United Kingdom)
2001-2015
Wellcome Trust
2015
Age UK
2012
Inserm
2011
Centre National de la Recherche Scientifique
2011
Institute of Genetics
2011
Rare genetic variants contribute to complex disease risk; however, the abundance of rare in human populations remains unknown. We explored this spectrum variation by sequencing 202 genes encoding drug targets 14,002 individuals. find are abundant (1 every 17 bases) and geographically localized, so that even with large sample sizes, variant catalogs will be largely incomplete. used observed patterns estimate population growth parameters, proportion a given frequency class putatively...
BioMart Central Portal is a first of its kind, community-driven effort to provide unified access dozens biological databases spanning genomics, proteomics, model organisms, cancer data, ontology information and more. Anybody can contribute an independently maintained resource the Portal, allowing it be exposed shared with research community, linking other resources in portal. Users take advantage common interface quickly utilize different sources without learning new system for each. The...
The chromatin-associated protein WDR5 is a promising target for pharmacological inhibition in cancer. Drug discovery efforts center on the blockade of "WIN site" WDR5, well-defined pocket that amenable to small molecule inhibition. Various cancer contexts have been proposed be targets WIN site inhibitors, but lack understanding genes and primary effects inhibitors hampers their utility. Here, by potent we demonstrate links chromatin at cohort loci, including specific subset ribosome genes....
Abstract The European Molecular Biology Laboratory's Bioinformatics Institute (EMBL-EBI) is one of the world's leading sources public biomolecular data. Based at Wellcome Genome Campus in Hinxton, UK, EMBL-EBI six sites Laboratory (EMBL), Europe's only intergovernmental life sciences organisation. This overview summarises latest developments services provided by data resources to scientific communities globally. These aim ensure meet current and future needs these communities, accelerating...
The sequence of squid (Loligo forbesi) rhodopsin was determined by protein and cDNA sequencing. has close similarity to octopus rhodopsin, having an N-terminal region (residues 1-340) which resembles other guanine-nucleotide-binding (G-protein)-linked receptors a repetitive proline-rich C-terminus 340-452). Comparison the with those members G-protein-linked receptor superfamily reveals features we predict have both structural functional importance.
CRF exerts a key neuroregulatory control on the function of hypothalamic-pituitary-adrenal axis. These effects are thought to be mediated primarily through activation Gs-coupled plasma membrane receptors. In present study, we investigated receptors by sauvagine signaling pathways that converge phosphorylation transcription factor calcium/cAMP response element-binding protein (CREB). Studies were undertaken using CHO cell lines transfected with either rat CRF-1 or CRF-2α Signaling...
In this study, cyclometallated gold(III) compounds were evaluated for their capability to promote C-Se coupling reactions under biocompatible conditions, and chemoselectivity towards selenium-containing substrates compared sulfur-containing analogs. The exhibited varying degrees of selectivity compounds, with [Au(bnopy)Cl₂] showing rapid bond formation. Competitive selenium sulfur highlighted the preference selenium, especially [Au(Mephpy)Cl₂], even in presence excess substrates. This was...
Abstract Trials have shown promising clinical activity of the selective SYK inhibitor entospletinib in patients with high expressing HOXA9/MEIS1 acute leukemias. As development resistance mechanisms is a common problem use targeted drugs, we performed chemical library screen to identify drug sensitivities resistant AML cells. We identified that cells displayed an increased sensitivity glucocorticoids. Glucocorticoids are potent immunosuppressants which work part by inhibiting transcription...
Background and purpose: Several P2X 7 receptor antagonists are allosteric inhibitors exhibit species difference in potency. Furthermore, N 2 ‐(3,4‐difluorophenyl)‐ 1 ‐(2‐methyl‐5‐(1‐piperazinylmethyl)phenyl)glycinamide dihydrochloride (GW791343) exhibits negative effects at the human but is a positive modulator of rat receptor. In this study we have identified several regions that contribute to differences antagonist effects. Experimental approach: Chimeric human‐rat receptors were...
The yeast Smf1p Nramp manganese transporter is posttranslationally regulated by environmental manganese. stabilized at the cell surface with starvation, but largely degraded in vacuole physiological through a mechanism involving Rsp5p adaptor complex Bsd2p/Tre1p/Tre2p. We now describe an additional level of regulation that occurs toxicity from manganese, not other essential metals. This Smf1p-specific. As toxic triggers vacuolar degradation trafficking multivesicular body. However, does...
Increased adiponectin levels have been shown to be associated with a lower risk of type 2 diabetes. To understand the relations between genetic variation at adiponectin-encoding gene, ADIPOQ, and levels, subsequently its role in disease, we conducted deep resequencing experiment ADIPOQ 14,002 subjects, including 12,514 Europeans, 594 African Americans, 567 Indian Asians. We identified 296 single nucleotide polymorphisms (SNPs), 30 amino acid changes, carried out association analyses subset...
Abstract The striatum has been implicated as the site of action mediating neurotoxic effects interleukin‐1 (IL‐1) during ischemia. However, molecular mechanisms underlying these events have yet to be fully addressed. In present study, primary cultures rat striatal cells were used a model for study IL‐1 signaling pathways in striatum. Immunocytochemical analyses revealed that consisted mixture neurones and astrocytes demonstrated expression type I receptor (IL‐1RI) on both cell types....
The potential importance of prostaglandin H synthase (PGHS) in the genotoxicity fecapentaene-12 (fec-12) has been indicated by finding that non-steroidal anti-inflammatory agents (NSAIDs) block induction oxidative DNA base damage fec-12 HeLa cells. To further investigate role PGHS metabolic 'activation' and fec-12, we have measured: (i) oxygen uptake with purified preparations PGHS; (ii) single-strand breaks (SSBs) cells exposed to absence or presence inhibitors. Oxygen occurred...
ADME SARfari is a freely available web resource that enables comparative analyses of drug-disposition genes. It does so by integrating number publicly data sources, which have subsequently been used to build mining services, predictive tools and visualizations for drug metabolism researchers. The include the interactions small molecules with (absorption, distribution, excretion) proteins responsible transport molecules; pharmacokinetic (PK) data; protein sequences ADME-related molecular...
Several lines of evidence suggest that interleukin-1 (IL-1) acts directly on the central nervous system, probably within hypothalamus, causing effects such as fever, activation immune response and sickness behaviour. IL-1 has also been shown to be involved in aetiology several neuronal diseases, including neurodegeneration, stroke Alzheimer's disease. However, question whether full-length type I receptor (IL-1RI) is expressed human hypothalamus yet addressed. Using polymerase chain reaction,...