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Sökning: WFRF:(Jordan J) > (2020)

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2.
  • Bryois, J., et al. (författare)
  • Genetic identification of cell types underlying brain complex traits yields insights into the etiology of Parkinson’s disease
  • 2020
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 52:5, s. 482-493
  • Tidskriftsartikel (refereegranskat)abstract
    • Genome-wide association studies have discovered hundreds of loci associated with complex brain disorders, but it remains unclear in which cell types these loci are active. Here we integrate genome-wide association study results with single-cell transcriptomic data from the entire mouse nervous system to systematically identify cell types underlying brain complex traits. We show that psychiatric disorders are predominantly associated with projecting excitatory and inhibitory neurons. Neurological diseases were associated with different cell types, which is consistent with other lines of evidence. Notably, Parkinson’s disease was genetically associated not only with cholinergic and monoaminergic neurons (which include dopaminergic neurons) but also with enteric neurons and oligodendrocytes. Using post-mortem brain transcriptomic data, we confirmed alterations in these cells, even at the earliest stages of disease progression. Our study provides an important framework for understanding the cellular basis of complex brain maladies, and reveals an unexpected role of oligodendrocytes in Parkinson’s disease. © 2020, The Author(s), under exclusive licence to Springer Nature America, Inc.
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3.
  • Kattge, Jens, et al. (författare)
  • TRY plant trait database - enhanced coverage and open access
  • 2020
  • Ingår i: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188
  • Tidskriftsartikel (refereegranskat)abstract
    • Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
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4.
  • Duffy, J. M. N., et al. (författare)
  • Top 10 priorities for future infertility research: an international consensus development study
  • 2020
  • Ingår i: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 35:12, s. 2715-2724
  • Tidskriftsartikel (refereegranskat)abstract
    • STUDY QUESTION: Can the priorities for future research in infertility be identified? SUMMARY ANSWER: The top 10 research priorities for the four areas of male infertility, female and unexplained infertility, medically assisted reproduction and ethics, access and organization of care for people with fertility problems were identified. WHAT IS KNOWN ALREADY: Many fundamental questions regarding the prevention, management and consequences of infertility remain unanswered. This is a barrier to improving the care received by those people with fertility problems. STUDY DESIGN, SIZE, DURATION: Potential research questions were collated from an initial international survey, a systematic review of clinical practice guidelines and Cochrane systematic reviews. A rationalized list of confirmed research uncertainties was prioritized in an interim international survey. Prioritized research uncertainties were discussed during a consensus development meeting. Using a formal consensus development method, the modified nominal group technique, diverse stakeholders identified the top 10 research priorities for each of the categories male infertility, female and unexplained infertility, medically assisted reproduction and ethics, access and organization of care. PARTICIPANTS/MATERIALS, SETTING, METHODS: Healthcare professionals, people with fertility problems and others (healthcare funders, healthcare providers, healthcare regulators, research funding bodies and researchers) were brought together in an open and transparent process using formal consensus methods advocated by the James Lind Alliance. MAIN RESULTS AND THE ROLE OF CHANCE: The initial survey was completed by 388 participants from 40 countries, and 423 potential research questions were submitted. Fourteen clinical practice guidelines and 162 Cochrane systematic reviews identified a further 236 potential research questions. A rationalized list of 231 confirmed research uncertainties was entered into an interim prioritization survey completed by 317 respondents from 43 countries. The top 10 research priorities for each of the four categories male infertility, female and unexplained infertility (including age-related infertility, ovarian cysts, uterine cavity abnormalities and tubal factor infertility), medically assisted reproduction (including ovarian stimulation, IUI and IVF) and ethics, access and organization of care were identified during a consensus development meeting involving 41 participants from I I countries. These research priorities were diverse and seek answers to questions regarding prevention, treatment and the longer-term impact of infertility. They highlight the importance of pursuing research which has often been overlooked, including addressing the emotional and psychological impact of infertility, improving access to fertility treatment, particularly in lower resource settings and securing appropriate regulation. Addressing these priorities will require diverse research methodologies, including laboratory-based science, qualitative and quantitative research and population science. LIMITATIONS, REASONS FOR CAUTION: We used consensus development methods, which have inherent limitations, including the representativeness of the participant sample, methodological decisions informed by professional judgment and arbitrary consensus definitions. WIDER IMPLICATIONS OF THE FINDINGS: We anticipate that identified research priorities, developed to specifically highlight the most pressing clinical needs as perceived by healthcare professionals, people with fertility problems and others, will help research funding organizations and researchers to develop their future research agenda.
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5.
  • Hogan, K. A., et al. (författare)
  • Revealing the former bed of Thwaites Glacier using sea-floor bathymetry: implications for warm-water routing and bed controls on ice flow and buttressing
  • 2020
  • Ingår i: Cryosphere. - : Copernicus GmbH. - 1994-0416. ; 14:9, s. 2883-2908
  • Tidskriftsartikel (refereegranskat)abstract
    • The geometry of the sea floor immediately beyond Antarctica's marine-terminating glaciers is a fundamental control on warm-water routing, but it also describes former topographic pinning points that have been important for ice-shelf buttressing. Unfortunately, this information is often lacking due to the inaccessibility of these areas for survey, leading to modelled or interpolated bathymetries being used as boundary conditions in numerical modelling simulations. At Thwaites Glacier (TG) this critical data gap was addressed in 2019 during the first cruise of the International Thwaites Glacier Collaboration (ITGC) project. We present more than 2000 km(2) of new multibeam echo-sounder (MBES) data acquired in exceptional sea-ice conditions immediately offshore TG, and we update existing bathymetric compilations. The cross-sectional areas of sea-floor troughs are under-predicted by up to 40% or are not resolved at all where MBES data are missing, suggesting that calculations of trough capacity, and thus oceanic heat flux, may be significantly underestimated. Spatial variations in the morphology of topographic highs, known to be former pinning points for the floating ice shelf of TG, indicate differences in bed composition that are supported by landform evidence. We discuss links to ice dynamics for an overriding ice mass including a potential positive feedback mechanism where erosion of soft erodible highs may lead to ice-shelf ungrounding even with little or no ice thinning. Analyses of bed roughnesses and basal drag contributions show that the sea-floor bathymetry in front of TG is an analogue for extant bed areas. Ice flow over the sea-floor troughs and ridges would have been affected by similarly high basal drag to that acting at the grounding zone today. We conclude that more can certainly be gleaned from these 3D bathymetric datasets regarding the likely spatial variability of bed roughness and bed composition types underneath TG. This work also addresses the requirements of recent numerical ice-sheet and ocean modelling studies that have recognised the need for accurate and high-resolution bathymetry to determine warm-water routing to the grounding zone and, ultimately, for predicting glacier retreat behaviour.
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6.
  • Gresle, MM, et al. (författare)
  • Multiple sclerosis risk variants regulate gene expression in innate and adaptive immune cells
  • 2020
  • Ingår i: Life science alliance. - : Life Science Alliance, LLC. - 2575-1077. ; 3:7
  • Tidskriftsartikel (refereegranskat)abstract
    • At least 200 single-nucleotide polymorphisms (SNPs) are associated with multiple sclerosis (MS) risk. A key function that could mediate SNP-encoded MS risk is their regulatory effects on gene expression. We performed microarrays using RNA extracted from purified immune cell types from 73 untreated MS cases and 97 healthy controls and then performed Cis expression quantitative trait loci mapping studies using additive linear models. We describe MS risk expression quantitative trait loci associations for 129 distinct genes. By extending these models to include an interaction term between genotype and phenotype, we identify MS risk SNPs with opposing effects on gene expression in cases compared with controls, namely, rs2256814 MYT1 in CD4 cells (q = 0.05) and rs12087340 RF00136 in monocyte cells (q = 0.04). The rs703842 SNP was also associated with a differential effect size on the expression of the METTL21B gene in CD8 cells of MS cases relative to controls (q = 0.03). Our study provides a detailed map of MS risk loci that function by regulating gene expression in cell types relevant to MS.
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7.
  • Duffy, J. M. N., et al. (författare)
  • Standardizing definitions and reporting guidelines for the infertility core outcome set: an international consensus development study
  • 2020
  • Ingår i: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 35:12, s. 2735-2745
  • Tidskriftsartikel (refereegranskat)abstract
    • STUDY QUESTION: Can consensus definitions for the core outcome set for infertility be identified in order to recommend a standardized approach to reporting? SUMMARY ANSWER: Consensus definitions for individual core outcomes, contextual statements and a standardized reporting table have been developed. WHAT IS KNOWN ALREADY: Different definitions exist for individual core outcomes for infertility. This variation increases the opportunities for researchers to engage with selective outcome reporting, which undermines secondary research and compromises clinical practice guideline development. STUDY DESIGN, SIZE, DURATION: Potential definitions were identified by a systematic review of definition development initiatives and clinical practice guidelines and by reviewing Cochrane Gynaecology and Fertility Group guidelines. These definitions were discussed in a face-to-face consensus development meeting, which agreed consensus definitions. A standardized approach to reporting was also developed as part of the process. PARTICIPANTS/MATERIALS, SETTING, METHODS: Healthcare professionals, researchers and people with fertility problems were brought together in an open and transparent process using formal consensus development methods. MAIN RESULTS AND THE ROLE OF CHANCE: Forty-four potential definitions were inventoried across four definition development initiatives, including the Harbin Consensus Conference Workshop Group and International Committee for Monitoring Assisted Reproductive Technologies, 12 clinical practice guidelines and Cochrane Gynaecology and Fertility Group guidelines. Twenty-seven participants, from 11 countries, contributed to the consensus development meeting. Consensus definitions were successfully developed for all core outcomes. Specific recommendations were made to improve reporting. LIMITATIONS, REASONS FOR CAUTION: We used consensus development methods, which have inherent limitations. There was limited representation from low- and middle-income countries. WIDER IMPLICATIONS OF THE FINDINGS: A minimum data set should assist researchers in populating protocols, case report forms and other data collection tools. The generic reporting table should provide clear guidance to researchers and improve the reporting of their results within journal publications and conference presentations. Research funding bodies, the Standard Protocol Items: Recommendations for Interventional Trials statement, and over 80 specialty journals have committed to implementing this core outcome set.
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8.
  • Gemmell, Neil J., et al. (författare)
  • The tuatara genome reveals ancient features of amniote evolution
  • 2020
  • Ingår i: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 584:7821, s. 403-409
  • Tidskriftsartikel (refereegranskat)abstract
    • The tuatara (Sphenodon punctatus)—the only living member of the reptilian order Rhynchocephalia (Sphenodontia), once widespread across Gondwana1,2—is an iconic species that is endemic to New Zealand2,3. A key link to the now-extinct stem reptiles (from which dinosaurs, modern reptiles, birds and mammals evolved), the tuatara provides key insights into the ancestral amniotes2,4. Here we analyse the genome of the tuatara, which—at approximately 5 Gb—is among the largest of the vertebrate genomes yet assembled. Our analyses of this genome, along with comparisons with other vertebrate genomes, reinforce the uniqueness of the tuatara. Phylogenetic analyses indicate that the tuatara lineage diverged from that of snakes and lizards around 250 million years ago. This lineage also shows moderate rates of molecular evolution, with instances of punctuated evolution. Our genome sequence analysis identifies expansions of proteins, non-protein-coding RNA families and repeat elements, the latter of which show an amalgam of reptilian and mammalian features. The sequencing of the tuatara genome provides a valuable resource for deep comparative analyses of tetrapods, as well as for tuatara biology and conservation. Our study also provides important insights into both the technical challenges and the cultural obligations that are associated with genome sequencing.
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9.
  • Manini, T. M., et al. (författare)
  • Identification of Sarcopenia Components That Discriminate Slow Walking Speed: A Pooled Data Analysis
  • 2020
  • Ingår i: Journal of the American Geriatrics Society. - : Wiley. - 0002-8614 .- 1532-5415. ; 68:7, s. 1419-1428
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND The Sarcopenia Definitions and Outcomes Consortium (SDOC) sought to identify cut points for muscle strength and body composition measures derived from dual-energy x-ray absorptiometry (DXA) that discriminate older adults with slow walking speed. This article presents the core analyses used to guide the SDOC position statements. DESIGN Cross-sectional data analyses of pooled data. SETTING University-based research assessment centers. PARTICIPANTS Community-dwelling men (n = 13,652) and women: (n = 5,115) with information on lean mass by DXA, grip strength (GR), and walking speed. MEASUREMENTS Thirty-five candidate sarcopenia variables were entered into sex-stratified classification and regression tree (CART) models to agnostically choose variables and cut points that discriminate slow walkers (<0.80 m/s). Models with alternative walking speed outcomes were also evaluated (<0.60 and <1.0 m/s and walking speed treated continuously). RESULTS CART models identified GR/body mass index (GRBMI) and GR/total body fat (GRTBF) as the primary discriminating variables for slowness in men and women, respectively. Men with GRBMI of 1.05 kg/kg/m(2)or less were approximately four times more likely to be slow walkers than those with GRBMI of greater than 1.05 kg/kg/m(2). Women with GRTBF of less than 0.65 kg/kg were twice as likely to be slow walkers than women with GRTBF of 0.65 kg/kg or greater. Models with alternative walking speed outcomes selected only functions of GR as primary discriminators of slowness in both men and women. DXA-derived lean mass measures did not consistently discriminate slow walkers. CONCLUSION GR with and without adjustments for body size and composition consistently discriminated older adults with slowness. CART models did not select DXA-based lean mass as a primary discriminator of slowness. These results were presented to an SDOC Consensus Panel, who used them and other information to develop the SDOC Position Statements.
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10.
  • Peace, Alexander L., et al. (författare)
  • A review of Pangaea dispersal and Large Igneous Provinces : In search of a causative mechanism
  • 2020
  • Ingår i: Earth-Science Reviews. - : Elsevier BV. - 0012-8252 .- 1872-6828. ; 206
  • Forskningsöversikt (refereegranskat)abstract
    • The breakup of Pangaea was accompanied by extensive, episodic, magmatic activity. Several Large Igneous Provinces (LIPs) formed, such as the Central Atlantic Magmatic Province (CAMP) and the North Atlantic Igneous Province (NAIP). Here, we review the chronology of Pangaea breakup and related large-scale magmatism. We review the Triassic formation of the Central Atlantic Ocean, the breakup between East and West Gondwana in the Middle Jurassic, the Early Cretaceous opening of the South Atlantic, the Cretaceous separation of India from Antarctica, and finally the formation of the North Atlantic in the Mesozoic-Cenozoic. We demonstrate that throughout the dispersal of Pangaea, major volcanism typically occurs distal from the locus of rift initiation and initial oceanic crust accretion. There is no location where extension propagates away from a newly formed LIP. Instead, LIPs are coincident with major lithosphere-scale shear movements, aborted rifts and splinters of continental crust rifted far out into the oceanic domain. These observations suggest that a fundamental reappraisal of the causes and consequences of breakup-related LIPs is in order.
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