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Sökning: WFRF:(Koch Marcus A.)

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1.
  • Klionsky, Daniel J., et al. (författare)
  • Guidelines for the use and interpretation of assays for monitoring autophagy
  • 2012
  • Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
  • Forskningsöversikt (refereegranskat)abstract
    • In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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2.
  • Docherty, Anna R, et al. (författare)
  • GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors.
  • 2023
  • Ingår i: The American journal of psychiatry. - : American Psychiatric Association Publishing. - 1535-7228 .- 0002-953X. ; 180:10, s. 723-738
  • Tidskriftsartikel (refereegranskat)abstract
    • Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and cross-validated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS meta-analysis of SA to date. Multi-ancestry and admixture-specific meta-analyses were conducted within groups of significant African, East Asian, and European ancestry admixtures.This study comprised 22 cohorts, including 43,871 SA cases and 915,025 ancestry-matched controls. Analytical methods across multi-ancestry and individual ancestry admixtures included inverse variance-weighted fixed-effects meta-analyses, followed by gene, gene-set, tissue-set, and drug-target enrichment, as well as summary-data-based Mendelian randomization with brain expression quantitative trait loci data, phenome-wide genetic correlation, and genetic causal proportion analyses.Multi-ancestry and European ancestry admixture GWAS meta-analyses identified 12 risk loci at p values <5×10-8. These loci were mostly intergenic and implicated DRD2, SLC6A9, FURIN, NLGN1, SOX5, PDE4B, and CACNG2. The multi-ancestry SNP-based heritability estimate of SA was 5.7% on the liability scale (SE=0.003, p=5.7×10-80). Significant brain tissue gene expression and drug set enrichment were observed. There was shared genetic variation of SA with attention deficit hyperactivity disorder, smoking, and risk tolerance after conditioning SA on both major depressive disorder and posttraumatic stress disorder. Genetic causal proportion analyses implicated shared genetic risk for specific health factors.This multi-ancestry analysis of suicide attempt identified several loci contributing to risk and establishes significant shared genetic covariation with clinical phenotypes. These findings provide insight into genetic factors associated with suicide attempt across ancestry admixture populations, in veteran and civilian populations, and in attempt versus death.
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3.
  • Mullins, Niamh, et al. (författare)
  • Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors
  • 2022
  • Ingår i: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 91:3, s. 313-327
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders.METHODS: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors.RESULTS: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged.CONCLUSIONS: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.
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4.
  • Leebens-Mack, James H., et al. (författare)
  • One thousand plant transcriptomes and the phylogenomics of green plants
  • 2019
  • Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 574:7780, s. 679-
  • Tidskriftsartikel (refereegranskat)abstract
    • Green plants (Viridiplantae) include around 450,000-500,000 species(1,2) of great diversity and have important roles in terrestrial and aquatic ecosystems. Here, as part of the One Thousand Plant Transcriptomes Initiative, we sequenced the vegetative transcriptomes of 1,124 species that span the diversity of plants in a broad sense (Archaeplastida), including green plants (Viridiplantae), glaucophytes (Glaucophyta) and red algae (Rhodophyta). Our analysis provides a robust phylogenomic framework for examining the evolution of green plants. Most inferred species relationships are well supported across multiple species tree and supermatrix analyses, but discordance among plastid and nuclear gene trees at a few important nodes highlights the complexity of plant genome evolution, including polyploidy, periods of rapid speciation, and extinction. Incomplete sorting of ancestral variation, polyploidization and massive expansions of gene families punctuate the evolutionary history of green plants. Notably, we find that large expansions of gene families preceded the origins of green plants, land plants and vascular plants, whereas whole-genome duplications are inferred to have occurred repeatedly throughout the evolution of flowering plants and ferns. The increasing availability of high-quality plant genome sequences and advances in functional genomics are enabling research on genome evolution across the green tree of life.
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5.
  • Hendriks, Kasper P., et al. (författare)
  • Global Brassicaceae phylogeny based on filtering of 1,000-gene dataset
  • 2023
  • Ingår i: Current Biology. - : Elsevier. - 0960-9822 .- 1879-0445. ; 33:19, s. 4052-4068
  • Tidskriftsartikel (refereegranskat)abstract
    • The mustard family (Brassicaceae) is a scientifically and economically important family, containing the model plant Arabidopsis thaliana and numerous crop species that feed billions worldwide. Despite its relevance, most phylogenetic trees of the family are incompletely sampled and often contain poorly supported branches. Here, we present the most complete Brassicaceae genus-level family phylogenies to date (Bras-sicaceae Tree of Life or BrassiToL) based on nuclear (1,081 genes, 319 of the 349 genera; 57 of the 58 tribes) and plastome (60 genes, 265 genera; all tribes) data. We found cytonuclear discordance between the two, which is likely a result of rampant hybridization among closely and more distantly related lineages. To eval-uate the impact of such hybridization on the nuclear phylogeny reconstruction, we performed five different gene sampling routines, which increasingly removed putatively paralog genes. Our cleaned subset of 297 genes revealed high support for the tribes, whereas support for the main lineages (supertribes) was moder-ate. Calibration based on the 20 most clock-like nuclear genes suggests a late Eocene to late Oligocene origin of the family. Finally, our results strongly support a recently published new family classification, dividing the family into two subfamilies (one with five supertribes), together representing 58 tribes. This includes five recently described or re-established tribes, including Arabidopsideae, a monogeneric tribe accommodating Arabidopsis without any close relatives. With a worldwide community of thousands of researchers working on Brassicaceae and its diverse members, our new genus-level family phylogeny will be an indispensable tool for studies on biodiversity and plant biology.
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6.
  • Plue, Jan, et al. (författare)
  • European soil seed bank communities across a climate and land-cover gradient
  • 2020
  • Annan publikationabstract
    • This is the data set used for the publication Buffering effects of soil seed banks on plant community composition in response to land use and climate, published in the journal Global Ecology and Biogeography.Aim.Climate and land use are key determinants of biodiversity, with past and ongoing changes posing serious threats to global ecosystems. Unlike most other organism groups, plant species can possess dormant life-history stages such as soil seed banks, which may help plant communities to resist or at least postpone the detrimental impact of global changes. This study investigates the potential for soil seed banks to achieve this.Location. EuropeTime period. 1978 – 2014Major taxa studied. Flowering plantsMethods.Using a space-for-time/warming approach, we study plant species richness and composition in the herb layer and the soil seed bank in 2796 community plots from 54 datasets in managed grasslands, forests and intermediate, successional habitats across a climate gradient.Results.Soil seed banks held more species than the herb layer, being compositionally similar across habitats. Species richness was lower in forests and successional habitats compared to grasslands, with annual temperature range more important than mean annual temperature for determining richness. Climate and land use effects were generally less pronounced when plant community richness included seed bank species richness, while there was no clear effect of land use and climate on compositional similarity between the seed bank and the herb layer.Main conclusions.High seed bank diversity and compositional similarity between the herb layer and seed bank plant communities may provide a potentially important functional buffer against the impact of ongoing environmental changes on plant communities. This capacity could, however, be threatened by climate warming. Dormant life-history stages can therefore be important sources of diversity in changing environments, potentially underpinning already observed time-lags in plant community responses to global change. However, as soil seed banks themselves appear, albeit less, vulnerable to the same changes, their potential to buffer change can only be temporary, and major community shifts may still be expected.MethodsThis dataset is a collection of 41 published and 5 unpublished data sets, consisting of 2796 plots with corresponding seed bank and herb layer community data. Sampling effort varied across data sets, but involved sampling of the soil and subsequent germination trials in a greenhouse to determine seed bank composition. Herb layer communities were determined by the identification of plants in relevés. Please consult the readme file and published paper for further details.Usage NotesPlease contact database or individual data set authors for further information and collaboration when using the data set or any of its component parts. Please also note that some of these data sets have already been published alongside their orginal papers. Finally, please cite data and datasets according to community standards.
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7.
  • Auffret, Alistair G., et al. (författare)
  • More warm-adapted species in soil seed banks than in herb layer plant communities across Europe
  • 2023
  • Ingår i: Journal of Ecology. - : John Wiley & Sons. - 0022-0477 .- 1365-2745. ; 111:5, s. 1009-1020
  • Tidskriftsartikel (refereegranskat)abstract
    • Responses to climate change have often been found to lag behind the rate of warming that has occurred. In addition to dispersal limitation potentially restricting spread at leading range margins, the persistence of species in new and unsuitable conditions is thought to be responsible for apparent time-lags. Soil seed banks can allow plant communities to temporarily buffer unsuitable environmental conditions, but their potential to slow responses to long-term climate change is largely unknown. As local forest cover can also buffer the effects of a warming climate, it is important to understand how seed banks might interact with land cover to mediate community responses to climate change. We first related species-level seed bank persistence and distribution-derived climatic niches for 840 plant species. We then used a database of plant community data from grasslands, forests and intermediate successional habitats from across Europe to investigate relationships between seed banks and their corresponding herb layers in 2763 plots in the context of climate and land cover. We found that species from warmer climates and with broader distributions are more likely to have a higher seed bank persistence, resulting in seed banks that are composed of species with warmer and broader climatic distributions than their corresponding herb layers. This was consistent across our climatic extent, with larger differences (seed banks from even warmer climates relative to vegetation) found in grasslands. Synthesis. Seed banks have been shown to buffer plant communities through periods of environmental variability, and in a period of climate change might be expected to contain species reflecting past, cooler conditions. Here, we show that persistent seed banks often contain species with relatively warm climatic niches and those with wide climatic ranges. Although these patterns may not be primarily driven by species’ climatic adaptations, the prominence of such species in seed banks might still facilitate climate-driven community shifts. Additionally, seed banks may be related to ongoing trends regarding the spread of widespread generalist species into natural habitats, while cool-associated species may be at risk from both short- and long-term climatic variability and change. 
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8.
  • Plue, Jan, et al. (författare)
  • Buffering effects of soil seed banks on plant community composition in response to land use and climate
  • 2020
  • Ingår i: Global Ecology and Biogeography. - : Wiley. - 1466-822X .- 1466-8238. ; 30:1, s. 128-139
  • Tidskriftsartikel (refereegranskat)abstract
    • AimClimate and land use are key determinants of biodiversity, with past and ongoing changes posing serious threats to global ecosystems. Unlike most other organism groups, plant species can possess dormant life‐history stages such as soil seed banks, which may help plant communities to resist or at least postpone the detrimental impact of global changes. This study investigates the potential for soil seed banks to achieve this.Location Europe.Time period 1978–2014.Major taxa studied Flowering plantsMethodsUsing a space‐for‐time/warming approach, we study plant species richness and composition in the herb layer and the soil seed bank in 2,796 community plots from 54 datasets in managed grasslands, forests and intermediate, successional habitats across a climate gradient.ResultsSoil seed banks held more species than the herb layer, being compositionally similar across habitats. Species richness was lower in forests and successional habitats compared to grasslands, with annual temperature range more important than mean annual temperature for determining richness. Climate and land‐use effects were generally less pronounced when plant community richness included seed bank species richness, while there was no clear effect of land use and climate on compositional similarity between the seed bank and the herb layer.Main conclusionsHigh seed bank diversity and compositional similarity between the herb layer and seed bank plant communities may provide a potentially important functional buffer against the impact of ongoing environmental changes on plant communities. This capacity could, however, be threatened by climate warming. Dormant life‐history stages can therefore be important sources of diversity in changing environments, potentially underpinning already observed time‐lags in plant community responses to global change. However, as soil seed banks themselves appear, albeit less, vulnerable to the same changes, their potential to buffer change can only be temporary, and major community shifts may still be expected.
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