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  • 1
    In: Nature, Springer Science and Business Media LLC, Vol. 600, No. 7889 ( 2021-12-16), p. 472-477
    Abstract: The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-19 1,2 , host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases 3–7 . They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease.
    Type of Medium: Online Resource
    ISSN: 0028-0836 , 1476-4687
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    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
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    detail.hit.zdb_id: 1413423-8
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  • 2
    In: Nature, Springer Science and Business Media LLC, Vol. 607, No. 7917 ( 2022-07-07), p. 97-103
    Abstract: Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care 1 or hospitalization 2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling ( IL10RB and PLSCR1 ), leucocyte differentiation ( BCL11A ) and blood-type antigen secretor status ( FUT2 ). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase ( ATP11A ), and increased expression of a mucin ( MUC1 )—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules ( SELE , ICAM5 and CD209 ) and the coagulation factor F8 , all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease.
    Type of Medium: Online Resource
    ISSN: 0028-0836 , 1476-4687
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    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 120714-3
    detail.hit.zdb_id: 1413423-8
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  • 3
    In: Genome Biology, Springer Science and Business Media LLC, Vol. 17, No. 1 ( 2016-12)
    Type of Medium: Online Resource
    ISSN: 1474-760X
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2016
    detail.hit.zdb_id: 2040529-7
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  • 4
    Online Resource
    Online Resource
    Proceedings of the National Academy of Sciences ; 2019
    In:  Proceedings of the National Academy of Sciences Vol. 116, No. 49 ( 2019-12-03), p. 24729-24737
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 116, No. 49 ( 2019-12-03), p. 24729-24737
    Abstract: The order Coleoptera (beetles) is arguably the most speciose group of animals, but the evolutionary history of beetles, including the impacts of plant feeding (herbivory) on beetle diversification, remain poorly understood. We inferred the phylogeny of beetles using 4,818 genes for 146 species, estimated timing and rates of beetle diversification using 89 genes for 521 species representing all major lineages and traced the evolution of beetle genes enabling symbiont-independent digestion of lignocellulose using 154 genomes or transcriptomes. Phylogenomic analyses of these uniquely comprehensive datasets resolved previously controversial beetle relationships, dated the origin of Coleoptera to the Carboniferous, and supported the codiversification of beetles and angiosperms. Moreover, plant cell wall-degrading enzymes (PCWDEs) obtained from bacteria and fungi via horizontal gene transfers may have been key to the Mesozoic diversification of herbivorous beetles—remarkably, both major independent origins of specialized herbivory in beetles coincide with the first appearances of an arsenal of PCWDEs encoded in their genomes. Furthermore, corresponding (Jurassic) diversification rate increases suggest that these novel genes triggered adaptive radiations that resulted in nearly half of all living beetle species. We propose that PCWDEs enabled efficient digestion of plant tissues, including lignocellulose in cell walls, facilitating the evolution of uniquely specialized plant-feeding habits, such as leaf mining and stem and wood boring. Beetle diversity thus appears to have resulted from multiple factors, including low extinction rates over a long evolutionary history, codiversification with angiosperms, and adaptive radiations of specialized herbivorous beetles following convergent horizontal transfers of microbial genes encoding PCWDEs.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
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    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2019
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  • 5
    In: Sedimentology, Wiley, Vol. 67, No. 2 ( 2020-02), p. 1014-1044
    Abstract: This paper details and describes a suite of 143 sub‐seismic‐scale clastic injectites encountered within the early Cretaceous, early post‐rift of the deep‐lacustrine North Falkland Basin. The injectites, referred to here as the Sea Lion Injectite System, are encountered below, above and in between the hydrocarbon‐bearing, deep‐lacustrine turbidite sandstones of the Bleaker 30, Sea Lion North, Sea Lion, Casper and Beverley fans. Sedimentary structures are documented within the injectites including: planar laminations, mud‐clast imbrication and clast alignment. Clasts align along centimetre‐scale foresets formed through ripple‐scale bedform migration in a hydraulically‐open fracture. The style of flow within the injectite system is interpreted as initially through fluid turbulence during an open fracture phase, which was followed by a later stage where laminar flow dominated, most likely during the closing phase of the fracture system. The host rocks display evidence for ductile deformation, which along with ptygmatic folding of dykes and internally injected mud‐clasts, suggests a period of injection into relatively uncompacted sediments. Evidence for brittle fracturing, in the form of stepped margins may be indicative of a separate phase of emplacement into more‐compacted sediments. This variability in deformation styles is related to multi‐phased injection episodes into host strata at different stages of consolidation and lithification at shallow burial depths. Injectites have been identified in four stratigraphic groupings: above the Bleaker 30 Fan and within/above the Sea Lion North Fan; within the hydrocarbon‐bearing Sea Lion Fan; overlying the Sea Lion Fan; and above/below the hydrocarbon‐bearing Casper and Beverley fans. This spatial association with the hydrocarbon‐bearing fans of the North Falkland Basin is important, considering the ability of injectite networks to form effective fluid‐flow conduits in the subsurface. Consequently, the findings of this study will improve the characterization of sub‐seismic scale injectites (and therefore fluid conduits) within otherwise impermeable strata.
    Type of Medium: Online Resource
    ISSN: 0037-0746 , 1365-3091
    URL: Issue
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    Language: English
    Publisher: Wiley
    Publication Date: 2020
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    detail.hit.zdb_id: 206889-8
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  • 6
    In: Sedimentology, Wiley, Vol. 69, No. 4 ( 2022-06), p. 1891-1926
    Abstract: Hybrid event beds are texturally and compositionally‐diverse deposits preserved within deepwater settings. They are deposited by flows exhibiting ‘mixed behaviour’, forming complex successions of sandstone and mudstone, which are often challenging to predict. Hybrid event beds are documented in deep‐marine settings, where they have been thoroughly characterized, and are well‐known as effective fluid transmissibility barriers and baffles in reservoirs. By comparison, there are far‐fewer studies of hybrid event beds from deep‐lacustrine settings, where their character and distribution remains relatively under‐explored. In order to provide insights into these deposits, this study presents the detailed analysis of three‐dimensional seismic data, wireline logs and core from a series of ancient deep‐lacustrine fan systems in the North Falkland Basin. Results confirm that deep‐lacustrine hybrid event beds comprise the same idealized sequence of the ‘H1–H5’ divisions. However, in this study H3 ‘debrite’ units can be sub‐divided into ‘H3a–H3c’, based on: sharp or erosional intra‐H3 contacts, bulk lithology, mud‐content and discrete sedimentary textures. This study interprets the H3a–H3c sub‐units as the products of multiple flow components formed through significant rearward longitudinal flow transformation processes, during the emplacement of a single hybrid event bed. Hybrid event beds are observed within lobe fringes, where flow types, energies and transport mechanisms diversify as a result of flow transformation. The temporal context of hybrid event bed occurrences is considered in relation to stages of fan evolution, including: the Initiation; Growth (I); Growth (II); By‐pass; Abandonment; and Termination phases. Hybrid event beds are mainly found in either the initiation phase where flow interaction and erosion of initial substrates promoted mixed flow behaviour, or in the abandonment phase as facies belts retreated landward. The results of this study have important implications in terms of flow processes of hybrid event bed emplacement, in particular sub‐division of the H3 unit, as well as the prediction of hybrid event bed occurrence and character within ancient deep‐lacustrine fan settings, in general.
    Type of Medium: Online Resource
    ISSN: 0037-0746 , 1365-3091
    URL: Issue
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    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2020955-1
    detail.hit.zdb_id: 206889-8
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  • 7
    In: Global Ecology and Biogeography, Wiley, Vol. 25, No. 11 ( 2016-11), p. 1367-1376
    Abstract: We propose and test a climate tolerance and trait choice hypothesis of urban macroecological variation in which strong filtering associated with low winter temperatures restricts urban biodiversity while weak filtering associated with warmer temperatures and irrigation allows dispersal of species from a global source pool, thereby increasing urban biodiversity. Location Twenty cities across the USA and Canada. Methods We examined variation in tree community taxonomic diversity, origins and production of an aesthetic ecosystem service trait in a cross‐section of urban field surveys. We correlated urban tree community composition indicators with a key climate restriction, namely mean minimum winter temperature, and evaluated alternative possible drivers: precipitation, summer maximum temperature, population size and the percentage of adults with a college education. Results Species accumulation curves differed substantially among cities, with observed richness varying from 22 to 122 species. Similarities in tree communities decreased exponentially with increases in climatic differences. Ordination of tree communities showed strong separation among cities with component axes correlated with minimum winter temperature and annual precipitation. Variation among urban tree communities in richness, origins and the provisioning of an aesthetic ecosystem service were all correlated with minimum winter temperature. Main conclusions The urban climate tolerance and trait choice hypothesis provides a coherent mechanism to explain the large variation among urban tree communities resulting from an interacting environment, species and human decisions. Reconciling the feedbacks between human decision making and biophysical limitations provides a foundation for an urban ecological theory that can better understand and predict the dynamics of other linked biotic communities, associated ecosystem dynamics and resulting services provided to urban residents.
    Type of Medium: Online Resource
    ISSN: 1466-822X , 1466-8238
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2016
    detail.hit.zdb_id: 1479787-2
    detail.hit.zdb_id: 2021283-5
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  • 8
    In: physica status solidi c, Wiley, Vol. 9, No. 12 ( 2012-12), p. 2247-2250
    Abstract: Photoluminescence (PL), PL lifetime, and radioluminescence (RL) measurements were made on LaF 3 nanoparticles doped with Eu 3+ or Sm 3+ . The radiative lifetimes decreased with increasing rare earth concentrations, which can be attributed to energy transfer to the surface of the nanoparticles followed by non‐radiative recombination. The RL signal increases with increasing concentration for Eu 3+ concentrations up to 20% Eu 3+ but it saturates and disappears for 〉 10% Sm 3+ . A dose‐independent RL was observed up to 10 kGy during continual X‐ray irradiation for Eu 3+ and Sm 3+ doped nanoparticles, which is advantageous for real time dosimetry applications (© 2012 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
    Type of Medium: Online Resource
    ISSN: 1862-6351 , 1610-1642
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2012
    detail.hit.zdb_id: 2105580-4
    detail.hit.zdb_id: 2102966-0
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  • 9
    Online Resource
    Online Resource
    Informa UK Limited ; 2014
    In:  Alcheringa: An Australasian Journal of Palaeontology Vol. 38, No. 4 ( 2014-10-02), p. 557-562
    In: Alcheringa: An Australasian Journal of Palaeontology, Informa UK Limited, Vol. 38, No. 4 ( 2014-10-02), p. 557-562
    Type of Medium: Online Resource
    ISSN: 0311-5518 , 1752-0754
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 2014
    detail.hit.zdb_id: 2272537-4
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  • 10
    Online Resource
    Online Resource
    Coleopterists Society ; 2004
    In:  The Coleopterists Bulletin Vol. 58, No. 4 ( 2004-12), p. 601-602
    In: The Coleopterists Bulletin, Coleopterists Society, Vol. 58, No. 4 ( 2004-12), p. 601-602
    Type of Medium: Online Resource
    ISSN: 0010-065X , 1938-4394
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    Language: English
    Publisher: Coleopterists Society
    Publication Date: 2004
    detail.hit.zdb_id: 2175913-3
    SSG: 12
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