| 1. |
- Alexander, Stephen P. H., et al.
(författare)
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The Concise Guide to PHARMACOLOGY 2023/24: G protein-coupled receptors
- 2023
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Ingår i: BRITISH JOURNAL OF PHARMACOLOGY. - : British pharmacological society. - 0007-1188 .- 1476-5381. ; 180, s. S23-S144
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Tidskriftsartikel (refereegranskat)abstract
- The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and about 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at . G protein-coupled receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2023, and supersedes data presented in the 2021/22, 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.
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| 2. |
- Christopoulos, Arthur, et al.
(författare)
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THE CONCISE GUIDE TO PHARMACOLOGY 2021/22: G protein-coupled receptors.
- 2021
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Ingår i: British journal of pharmacology. - : Wiley. - 1476-5381 .- 0007-1188. ; 178 Suppl 1, s. S27-S156
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Forskningsöversikt (refereegranskat)abstract
- The Concise Guide to PHARMACOLOGY 2021/22 is the fifth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of nearly 1900 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes over 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/bph.15538. G protein-coupled receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2021, and supersedes data presented in the 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.
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| 3. |
- Roselli, Carolina, et al.
(författare)
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Multi-ethnic genome-wide association study for atrial fibrillation
- 2018
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 50:9, s. 1225-1233
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Tidskriftsartikel (refereegranskat)abstract
- Atrial fibrillation (AF) affects more than 33 million individuals worldwide(1) and has a complex heritability(2). We conducted the largest meta-analysis of genome-wide association studies (GWAS) for AF to date, consisting of more than half a million individuals, including 65,446 with AF. In total, we identified 97 loci significantly associated with AF, including 67 that were novel in a combined-ancestry analysis, and 3 that were novel in a European-specific analysis. We sought to identify AF-associated genes at the GWAS loci by performing RNA-sequencing and expression quantitative trait locus analyses in 101 left atrial samples, the most relevant tissue for AF. We also performed transcriptome-wide analyses that identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci implicate genes enriched within cardiac developmental, electrophysiological, contractile and structural pathways. These results extend our understanding of the biological pathways underlying AF and may facilitate the development of therapeutics for AF.
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| 4. |
- Gardiner, Nicholas J., et al.
(författare)
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The crustal architecture of Myanmar imaged through zircon U-Pb, Lu-Hf and O isotopes : Tectonic and metallogenic implications
- 2018
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Ingår i: Gondwana Research. - : Elsevier BV. - 1342-937X .- 1878-0571. ; 62, s. 27-60
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Tidskriftsartikel (refereegranskat)abstract
- The Tethys margin in central and eastern Asia is comprised of continental terranesseparated by suture zones, some of which remain cryptic. Determining the crustal architecture, and therefore the geological history, of the Eastern Tethyan margin remains challenging. Sited in the heart of this region, Myanmar is a highly prospective but poorly explored minerals jurisdiction. A better understanding of Myanmar's mineralization can only be realized through a better understanding of its tectonic history, itself reflected in at least four major magmatic belts. The Eastern and the Main Range Provinces are associated with the Late Permian to Early Triassic closure of Palaeo-Tethys. The Mogok–Mandalay–Mergui Belt and Wuntho–Popa Arc are a response to the Eocene closure of Neo-Tethys. However, magmatic ages outside these two orogenic events are also recorded. We present new zirconU-Pb, Lu-Hf and O isotope data from magmatic rocks across Myanmar, which we append to the existing dataset to isotopically characterize Myanmar's magmatic belts. Eastern Province Permian I-type magmatism has evolved εHf (−10.9 to −6.4), whilst Main Range Province Triassic S-type magmatism also records evolved εHf (−13.5 to −8.8). The Mogok-Mandalay-Mergui Belt is here divided into the Tin Province and the Mogok Metamorphic Belt. The Tin Province hosts ca. 77–50 Ma magmatism with evolved εHf (−1.2 to −15.2), and δ18O of 5.6–8.3‰. The Mogok Metamorphic Belt exhibits a more complex magmatic and metamorphic history, and granitoids record Jurassic, Late Cretaceous, and Eocene to Miocene phases of magmatism, all of which exhibit evolved εHf values between −4.6 and −17.6, and δ18O between 6.3 and 9.2‰. From the Tagaung-Myitkyina Belt, we report a magmatic age of 172 Ma and εHf of 18.1 to 10.8. To accommodate the geological evidence, we propose a tectonic model for Myanmar involving a greater Sibumasu – where the documented zircon isotopic variations reflect compositional variations in magmatic source – and invoke the role of a Tengchong Block. The Baoshan Block and Greater Sibumasu were likely assembled on or before the Triassic, a former Andean margin and suture which may lie across the Northern Shan Plateau, and reflected in isotopic differences between the northern and southern parts of the Mogok Metamorphic Belt. This contiguous Sibumasu–Baoshan Block then sutured onto the Indochina margin in the Late Triassic. We propose that a Tengchong Block within Myanmar provides for a southerly termination of the Meso-Tethys suture immediately north of the Mogok area. A discrete Tengchong Block may explain a discontinuous arc of Late Triassic to Jurassic I-type magmatism in central Myanmar, representing an Andean-type margin sited above a subducting Meso-Tethys on the margin of Sibumasu. The Tengchong Block sutured onto Greater Sibumasu before the Late Cretaceous, after which subduction of Neo-Tethys drove the magmatism of the Wuntho-Popa Arc and ultimately that of the Tin Province. The metallogenic character of granite belts in Myanmar reflects the crustal architecture of the region, which is remarkable for its prolific endowment of granite-hosted Sn-W mineralization in two quite distinct granite belts related to sequential Indosinian and Himalayan orogenesis.
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| 5. |
- Charney, Alexander W, et al.
(författare)
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Contribution of Rare Copy Number Variants to Bipolar Disorder Risk Is Limited to Schizoaffective Cases.
- 2019
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Ingår i: Biological psychiatry. - : Elsevier BV. - 1873-2402 .- 0006-3223. ; 86:2, s. 110-119
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Tidskriftsartikel (refereegranskat)abstract
- Genetic risk for bipolar disorder (BD) is conferred through many common alleles, while a role for rare copy number variants (CNVs) is less clear. Subtypes of BD including schizoaffective disorder bipolar type (SAB), bipolar I disorder (BD I), and bipolar II disorder (BD II) differ according to the prominence and timing of psychosis, mania, and depression. The genetic factors contributing to the combination of symptoms among these subtypes are poorly understood.Rare large CNVs were analyzed in 6353 BD cases (3833 BD I [2676 with psychosis, 850 without psychosis, and 307 with unknown psychosis history], 1436 BD II, 579 SAB, and 505 BD not otherwise specified) and 8656 controls. CNV burden and a polygenic risk score (PRS) for schizophrenia were used to evaluate the relative contributions of rare and common variants to risk of BD, BD subtypes, and psychosis.CNV burden did not differ between BD and controls when treated as a single diagnostic entity. However, burden in SAB was increased relative to controls (p = .001), BD I (p = .0003), and BD II (p = .0007). Burden and schizophrenia PRSs were increased in SAB compared with BD I with psychosis (CNV p = .0007, PRS p = .004), and BD I without psychosis (CNV p = .0004, PRS p = 3.9 × 10-5). Within BD I, psychosis was associated with increased schizophrenia PRSs (p = .005) but not CNV burden.CNV burden in BD is limited to SAB. Rare and common genetic variants may contribute differently to risk for psychosis and perhaps other classes of psychiatric symptoms.
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| 6. |
- Smith, Gustav, et al.
(författare)
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Discovery of Genetic Variation on Chromosome 5q22 Associated with Mortality in Heart Failure
- 2016
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Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 12:5
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Tidskriftsartikel (refereegranskat)abstract
- Failure of the human heart to maintain sufficient output of blood for the demands of the body, heart failure, is a common condition with high mortality even with modern therapeutic alternatives. To identify molecular determinants of mortality in patients with new-onset heart failure, we performed a meta-analysis of genome-wide association studies and follow-up genotyping in independent populations. We identified and replicated an association for a genetic variant on chromosome 5q22 with 36% increased risk of death in subjects with heart failure (rs9885413, P = 2.7x10-9). We provide evidence from reporter gene assays, computational predictions and epigenomic marks that this polymorphism increases activity of an enhancer region active in multiple human tissues. The polymorphism was further reproducibly associated with a DNA methylation signature in whole blood (P = 4.5x10-40) that also associated with allergic sensitization and expression in blood of the cytokine TSLP (P = 1.1x10-4). Knockdown of the transcription factor predicted to bind the enhancer region (NHLH1) in a human cell line (HEK293) expressing NHLH1 resulted in lower TSLP expression. In addition, we observed evidence of recent positive selection acting on the risk allele in populations of African descent. Our findings provide novel genetic leads to factors that influence mortality in patients with heart failure.
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