| 1. |
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- 2019
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Wang, Li-San, et al.
(författare)
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Rarity of the Alzheimer Disease-Protective APP A673T Variant in the United States.
- 2015
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Ingår i: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 72:2
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Tidskriftsartikel (refereegranskat)abstract
- Recently, a rare variant in the amyloid precursor protein gene (APP) was described in a population from Iceland. This variant, in which alanine is replaced by threonine at position 673 (A673T), appears to protect against late-onset Alzheimer disease (AD). We evaluated the frequency of this variant in AD cases and cognitively normal controls to determine whether this variant will significantly contribute to risk assessment in individuals in the United States.
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| 3. |
- Lorenzen, Eline D., et al.
(författare)
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Species-specific responses of Late Quaternary megafauna to climate and humans
- 2011
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 479:7373, s. 359-364
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Tidskriftsartikel (refereegranskat)abstract
- Despite decades of research, the roles of climate and humans in driving the dramatic extinctions of large-bodied mammals during the Late Quaternary period remain contentious. Here we use ancient DNA, species distribution models and the human fossil record to elucidate how climate and humans shaped the demographic history of woolly rhinoceros, woolly mammoth, wild horse, reindeer, bison and musk ox. We show that climate has been a major driver of population change over the past 50,000 years. However, each species responds differently to the effects of climatic shifts, habitat redistribution and human encroachment. Although climate change alone can explain the extinction of some species, such as Eurasian musk ox and woolly rhinoceros, a combination of climatic and anthropogenic effects appears to be responsible for the extinction of others, including Eurasian steppe bison and wild horse. We find no genetic signature or any distinctive range dynamics distinguishing extinct from surviving species, emphasizing the challenges associated with predicting future responses of extant mammals to climate and human-mediated habitat change.
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| 4. |
- Sung, Yun Ju, et al.
(författare)
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A multi-ancestry genome-wide study incorporating gene-smoking interactions identifies multiple new loci for pulse pressure and mean arterial pressure
- 2019
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Ingår i: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 28:15, s. 2615-2633
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Tidskriftsartikel (refereegranskat)abstract
- Elevated blood pressure (BP), a leading cause of global morbidity and mortality, is influenced by both genetic and lifestyle factors. Cigarette smoking is one such lifestyle factor. Across five ancestries, we performed a genome-wide gene–smoking interaction study of mean arterial pressure (MAP) and pulse pressure (PP) in 129 913 individuals in stage 1 and follow-up analysis in 480 178 additional individuals in stage 2. We report here 136 loci significantly associated with MAP and/or PP. Of these, 61 were previously published through main-effect analysis of BP traits, 37 were recently reported by us for systolic BP and/or diastolic BP through gene–smoking interaction analysis and 38 were newly identified (P < 5 × 10−8, false discovery rate < 0.05). We also identified nine new signals near known loci. Of the 136 loci, 8 showed significant interaction with smoking status. They include CSMD1 previously reported for insulin resistance and BP in the spontaneously hypertensive rats. Many of the 38 new loci show biologic plausibility for a role in BP regulation. SLC26A7 encodes a chloride/bicarbonate exchanger expressed in the renal outer medullary collecting duct. AVPR1A is widely expressed, including in vascular smooth muscle cells, kidney, myocardium and brain. FHAD1 is a long non-coding RNA overexpressed in heart failure. TMEM51 was associated with contractile function in cardiomyocytes. CASP9 plays a central role in cardiomyocyte apoptosis. Identified only in African ancestry were 30 novel loci. Our findings highlight the value of multi-ancestry investigations, particularly in studies of interaction with lifestyle factors, where genomic and lifestyle differences may contribute to novel findings.
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| 5. |
- 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
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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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| 6. |
- Anderson, Tovi M., et al.
(författare)
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Molecular and Evolutionary History of Melanism in North American Gray Wolves
- 2009
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 323:5919, s. 1339-1343
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Tidskriftsartikel (refereegranskat)abstract
- Morphological diversity within closely related species is an essential aspect of evolution and adaptation. Mutations in the Melanocortin 1 receptor (Mc1r) gene contribute to pigmentary diversity in natural populations of fish, birds, and many mammals. However, melanism in the gray wolf, Canis lupus, is caused by a different melanocortin pathway component, the K locus, that encodes a beta-defensin protein that acts as an alternative ligand for Mc1r. We show that the melanistic K locus mutation in North American wolves derives from past hybridization with domestic dogs, has risen to high frequency in forested habitats, and exhibits a molecular signature of positive selection. The same mutation also causes melanism in the coyote, Canis latrans, and in Italian gray wolves, and hence our results demonstrate how traits selected in domesticated species can influence the morphological diversity of their wild relatives.
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| 7. |
- Barsh, Gregory S., et al.
(författare)
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How the Gray Wolf Got Its Color - Response
- 2009
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 325:5936, s. 34-34
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Tidskriftsartikel (refereegranskat)
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| 8. |
- 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
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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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| 9. |
- Ellinger, Eleunthia, Wong, et al.
(författare)
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Skin in the Game : The Transformational Potential of Decentralized Autonomous Organizations
- 2024
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Ingår i: MIS Quarterly: Management Information Systems. - : Management Information Systems Research Center. - 2162-9730 .- 0276-7783. ; 48:1, s. 245-272
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Tidskriftsartikel (refereegranskat)abstract
- Decentralized autonomous organizations (DAOs)—collectively owned human-machine systems deployed on a blockchain that self-govern through smart contracts and the voluntary contributions of autonomous community members—exhibit the potential to facilitate collective action in managing digital commons. Yet the promise of decentralization and collective action is difficult to sustain. To this end, this paper critically examines the transformational potential of DAOs in the case of decentralized finance. Using a polycentric governance lens, we contribute to the literature on technology-enabled forms of organizing with a model explaining the transformational potential of DAOs to facilitate collective action in digital commons. Our study highlights that (1) DAOs are a new form of organizing enabled by blockchain technology in which individuals are free to pursue their objectives within a general system of rules enforced by smart contracts, (2) collective action for managing digital commons can be sustained through a set of three mechanisms—sustained participation, collective direction, and scaled organizing, and (3) DAOs tend to strike a balance between centralized and fully decentralized or community-based governance by implementing a polycentric governance system involving a combination of human and machine agency that creates skin in the game.
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| 10. |
- Mähring, Magnus, et al.
(författare)
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Paradoxes and the nature of ambidexterity in IT transformation programs
- 2015
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Ingår i: Information Systems Research. - : INFORMS (Institute for Operations Research and Management Sciences). - 1047-7047 .- 1526-5536. ; 26:1, s. 57-80
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Tidskriftsartikel (refereegranskat)abstract
- Though information technology (IT) transformation programs are gaining in importance, we know little about the nature of the challenges involved in such programs and how to manage them. Using grounded theory methodology, we conducted a multiyear case study of a large IT transformation program in a major commercial bank, during which we encountered the interrelated themes of paradoxes and ambidexterity. Grounded in our case, we construct a substantive theory of ambidexterity in IT transformation programs that identifies and explains the paradoxes that managers need to resolve in IT transformation programs. The ambidexterity areas we identified are (1) IT portfolio decisions (i.e., IT efficiency versus IT innovation), (2) IT platform design (i.e., IT standardization versus IT differentiation), (3) IT architecture change (i.e., IT integration versus IT replacement), (4) IT program planning (i.e., IT program agility versus IT project stability), (5) IT program governance (i.e., IT program control versus IT project autonomy), and (6) IT program delivery (i.e., IT program coordination versus IT project isolation). What weaves these six areas together is the combined need for IT managers to employ ambidextrous resolution strategies to ensure short-term IT contributions and continuous progress of IT projects while simultaneously working toward IT transformation program success as a foundation for IT-enabled business transformation. However, in addition to this commonality, we find that the nature of paradoxical tensions differs across the six areas and requires slightly different management strategies for paradox resolution. Ambidexterity areas (1), (2), and (3) are associated with IT transformation strategizing and, in addition to balancing short- and long-term goals, require the mutual accommodation and blending of business and IT interests in the spirit of IT-business partnering to achieve IT-enabled business change and IT-based competitiveness. Ambidexterity areas (4), (5), and (6) are associated with IT program and project execution and, in addition to balancing short- and long-term requirements, require a recurrent and dynamic act of balancing "local" needs at the IT project level and "global" needs at the IT program level.
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| 11. |
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