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- Binder, J., et al.
(author)
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Machine learning prediction and tau-based screening identifies potential Alzheimer's disease genes relevant to immunity
- 2022
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In: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 5:1
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Journal article (peer-reviewed)abstract
- With increased research funding for Alzheimer's disease (AD) and related disorders across the globe, large amounts of data are being generated. Several studies employed machine learning methods to understand the ever-growing omics data to enhance early diagnosis, map complex disease networks, or uncover potential drug targets. We describe results based on a Target Central Resource Database protein knowledge graph and evidence paths transformed into vectors by metapath matching. We extracted features between specific genes and diseases, then trained and optimized our model using XGBoost, termed MPxgb(AD). To determine our MPxgb(AD) prediction performance, we examined the top twenty predicted genes through an experimental screening pipeline. Our analysis identified potential AD risk genes: FRRS1, CTRAM, SCGB3A1, FAM92B/CIBAR2, and TMEFF2. FRRS1 and FAM92B are considered dark genes, while CTRAM, SCGB3A1, and TMEFF2 are connected to TREM2-TYROBP, IL-1 beta-TNF alpha, and MTOR-APP AD-risk nodes, suggesting relevance to the pathogenesis of AD. Jessica Binder et al. developed a machine learning model to discover potential drug targets for Alzheimer's disease. They validated their 20 top candidates in several in vitro models, and highlight FRRS1, CTRAM, SCGB3A1, FAM92B/CIBAR2, and TMEFF2 as potential AD risk genes.
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- Burli, S., et al.
(author)
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A common soil temperature threshold for the upper limit of alpine grasslands in European mountains
- 2021
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In: Alpine Botany. - : Springer Science and Business Media LLC. - 1664-2201 .- 1664-221X. ; 131, s. 41-52
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Journal article (peer-reviewed)abstract
- While climatic research about treeline has a long history, the climatic conditions corresponding to the upper limit of closed alpine grasslands remain poorly understood. Here, we propose a climatic definition for this limit, the 'grassline', in analogy to the treeline, which is based on the growing season length and the soil temperature. Eighty-seven mountain summits across ten European mountain ranges, covering three biomes (boreal, temperate, Mediterranean), were inventoried as part of the GLORIA project. Vascular plant cover was estimated visually in 326 plots of 1 x 1 m. Soil temperatures were measured in situ for 2-7 years, from which the length of the growing season and mean temperature were derived. The climatic conditions corresponding to 40% plant cover were defined as the thresholds for alpine grassland. Closed vegetation was present in locations with a mean growing season soil temperature warmer than 4.9 degrees C, or a minimal growing season length of 85 days, with the growing season defined as encompassing days with daily mean >= 1 degrees C. Hence, the upper limit of closed grasslands was associated with a mean soil temperature close to that previously observed at the treeline, and in accordance with physiological thresholds to growth in vascular plants. In contrast to trees, whose canopy temperature is coupled with air temperature, small-stature alpine plants benefit from the soil warmed by solar radiation and consequently, they can grow at higher elevations. Since substrate stability is necessary for grasslands to occur at their climatic limit, the grassline rarely appears as a distinct linear feature.
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- Staude, I. R., et al.
(author)
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Directional turnover towards larger-ranged plants over time and across habitats
- 2022
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In: Ecology Letters. - : Wiley. - 1461-023X .- 1461-0248. ; 25:2, s. 466-82
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Journal article (peer-reviewed)abstract
- Species turnover is ubiquitous. However, it remains unknown whether certain types of species are consistently gained or lost across different habitats. Here, we analysed the trajectories of 1827 plant species over time intervals of up to 78 years at 141 sites across mountain summits, forests, and lowland grasslands in Europe. We found, albeit with relatively small effect sizes, displacements of smaller- by larger-ranged species across habitats. Communities shifted in parallel towards more nutrient-demanding species, with species from nutrient-rich habitats having larger ranges. Because these species are typically strong competitors, declines of smaller-ranged species could reflect not only abiotic drivers of global change, but also biotic pressure from increased competition. The ubiquitous component of turnover based on species range size we found here may partially reconcile findings of no net loss in local diversity with global species loss, and link community-scale turnover to macroecological processes such as biotic homogenisation.
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- Winkler, M., et al.
(author)
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The rich sides of mountain summits - a pan-European view on aspect preferences of alpine plants
- 2016
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In: Journal of Biogeography. - : Wiley. - 0305-0270. ; 43:11, s. 2261-2273
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Journal article (peer-reviewed)abstract
- Aim In the alpine life zone, plant diversity is strongly determined by local topography and microclimate. We assessed the extent to which aspect and its relatedness to temperature affect plant species diversity, and the colonization and disappearance of species on alpine summits on a pan-European scale. Methods Vascular plant species and their percentage cover were recorded in permanent plots in each cardinal direction on 123 summits in 32 regions across Europe. For a subset from 17 regions, resurvey data and 6-year soil temperature series were available. Differences in temperature sum and Shannon index as well as species richness, colonization and disappearance of species among cardinal directions were analysed using linear mixed-effects and generalised mixed-effects models, respectively. Results Temperature sums were higher in east-and south-facing aspects than in the north-facing ones, while the west-facing ones were intermediate; differences were smallest in northern Europe. The patterns of temperature sums among aspects were consistent among years. In temperate regions, thermal differences were reflected by plant diversity, whereas this relationship was weaker or absent on Mediterranean and boreal mountains. Colonization of species was positively related to temperature on Mediterranean and temperate mountains, whereas disappearance of species was not related to temperature. Main conclusions Thermal differences caused by solar radiation determine plant species diversity on temperate mountains. Advantages for plants on eastern slopes may result from the combined effects of a longer diurnal period of radiation due to convection cloud effects in the afternoon and the sheltered position against the prevailing westerly winds. In northern Europe, long summer days and low sun angles can even out differences among aspects. On Mediterranean summits, summer drought may limit species numbers on the warmer slopes. Warmer aspects support a higher number of colonization events. Hence, aspect can be a principal determinant of the pace of climate-induced migration processes.
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- Avram, S., et al.
(author)
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DrugCentral 2021 supports drug discovery and repositioning
- 2021
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In: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 49:D1
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Journal article (peer-reviewed)abstract
- DrugCentral is a public resource (http://drugcentral.org) that serves the scientific community by providing up-to-date drug information, as described in previous papers. The current release includes 109 newly approved (October 2018 through March 2020) active pharmaceutical ingredients in the US, Europe, Japan and other countries; and two molecular entities (e.g. mefuparib) of interest for COVID19. New additions include a set of pharmacokinetic properties for similar to 1000 drugs, and a sex-based separation of side effects, processed from FAERS (FDA Adverse Event Reporting System); as well as a drug repositioning prioritization scheme based on the market availability and intellectual property rights forFDA approved drugs. In the context of the COVID19 pandemic, we also incorporated REDIAL-2020, a machine learning platform that estimates anti-SARS-CoV-2 activities, as well as the `drugs in news' feature offers a brief enumeration of the most interesting drugs at the present moment. The full database dump and data files are available for download fromthe DrugCentral web portal.
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- Bologa, C. G., et al.
(author)
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Emerging trends in the discovery of natural product antibacterials
- 2013
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In: Current Opinion in Pharmacology. - : Elsevier BV. - 1471-4892. ; 13:5, s. 678-687
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Journal article (peer-reviewed)abstract
- This article highlights current trends and advances in exploiting natural sources for the deployment of novel and potent anti-infective countermeasures. The key challenge is to therapeutically target bacterial pathogens that exhibit a variety of puzzling and evolutionarily complex resistance mechanisms. Special emphasis is given to the strengths, weaknesses, and opportunities in the natural product antibacterial drug discovery arena, and to emerging applications driven by advances in bioinformatics, chemical biology, and synthetic biology in concert with exploiting bacterial phenotypes. These efforts have identified a critical mass of natural product antibacterial lead compounds and discovery technologies with high probability of successful implementation against emerging bacterial pathogens.
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- Oprea, Tudor I, et al.
(author)
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Unexplored therapeutic opportunities in the human genome
- 2018
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In: Nature Reviews Drug Discovery. - : Springer Science and Business Media LLC. - 1474-1776 .- 1474-1784. ; 17:5, s. 317-332
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Journal article (peer-reviewed)abstract
- A large proportion of biomedical research and the development of therapeutics is focused on a small fraction of the human genome. In a strategic effort to map the knowledge gaps around proteins encoded by the human genome and to promote the exploration of currently understudied, but potentially druggable, proteins, the US National Institutes of Health launched the Illuminating the Druggable Genome (IDG) initiative in 2014. In this article, we discuss how the systematic collection and processing of a wide array of genomic, proteomic, chemical and disease-related resource data by the IDG Knowledge Management Center have enabled the development of evidence-based criteria for tracking the target development level (TDL) of human proteins, which indicates a substantial knowledge deficit for approximately one out of three proteins in the human proteome. We then present spotlights on the TDL categories as well as key drug target classes, including G protein-coupled receptors, protein kinases and ion channels, which illustrate the nature of the unexplored opportunities for biomedical research and therapeutic development.
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