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1.
  • Arnold, Polly L., et al. (författare)
  • Controlled Photocatalytic Hydrocarbon Oxidation by Uranyl Complexes
  • 2019
  • Ingår i: ChemCatChem. - : Wiley-VCH Verlagsgesellschaft. - 1867-3880 .- 1867-3899. ; 11:16, s. 3786-3790
  • Tidskriftsartikel (refereegranskat)abstract
    • Controlled, photocatalytic C-H bond activations are key reactions in the toolkits of the modern synthetic chemist. While it is known that the uranyl(VI) ion, [(UO2)-O-VI](2+), the environmentally dominant form of uranium, is photoactive, most literature examines its luminescent properties, neglecting its potential synthetic utility for photocatalytic C-H bond cleavage. Here, we synthesise and fully characterise an air-stable and hydrocarbon-soluble uranyl phenanthroline complex, [(UO2)-O-VI(NO3)(2)(Ph(2)phen)], U-Ph2phen, and demonstrate that it can catalytically abstract hydrogen atoms from a variety of organic substrates under visible light irradiation. We show that the commercially available parent complex, uranyl nitrate ([(UO2)-O-VI(NO3)(2)(OH2)(2)]center dot 4H(2)O; U-NO3), is also competent, but from electronic spectroscopy we attribute the higher rates and selectivity of U-Ph2phen to ligand-mediated electronic effects. Ketones are selectively formed over other oxygenated products (alcohols, etc.), and the catalytic oxidation of substrates containing a benzylic C-H position is particularly improved for U-Ph2phen. We also show uranyl-mediated photocatalytic C-C bond cleavage in a model lignin compound for the first time.
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  • Botvinik-Nezer, Rotem, et al. (författare)
  • Variability in the analysis of a single neuroimaging dataset by many teams
  • 2020
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 582, s. 84-88
  • Tidskriftsartikel (refereegranskat)abstract
    • Data analysis workflows in many scientific domains have become increasingly complex and flexible. Here we assess the effect of this flexibility on the results of functional magnetic resonance imaging by asking 70 independent teams to analyse the same dataset, testing the same 9 ex-ante hypotheses(1). The flexibility of analytical approaches is exemplified by the fact that no two teams chose identical workflows to analyse the data. This flexibility resulted in sizeable variation in the results of hypothesis tests, even for teams whose statistical maps were highly correlated at intermediate stages of the analysis pipeline. Variation in reported results was related to several aspects of analysis methodology. Notably, a meta-analytical approach that aggregated information across teams yielded a significant consensus in activated regions. Furthermore, prediction markets of researchers in the field revealed an overestimation of the likelihood of significant findings, even by researchers with direct knowledge of the dataset(2-5). Our findings show that analytical flexibility can have substantial effects on scientific conclusions, and identify factors that may be related to variability in the analysis of functional magnetic resonance imaging. The results emphasize the importance of validating and sharing complex analysis workflows, and demonstrate the need for performing and reporting multiple analyses of the same data. Potential approaches that could be used to mitigate issues related to analytical variability are discussed. The results obtained by seventy different teams analysing the same functional magnetic resonance imaging dataset show substantial variation, highlighting the influence of analytical choices and the importance of sharing workflows publicly and performing multiple analyses.
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5.
  • Dussex, Nicolas, et al. (författare)
  • Adaptation to the High-Arctic island environment despite long-term reduced genetic variation in Svalbard reindeer
  • 2023
  • Ingår i: iScience. - 2589-0042. ; 26:10
  • Tidskriftsartikel (refereegranskat)abstract
    • Typically much smaller in number than their mainland counterparts, island populations are ideal systems to investigate genetic threats to small populations. The Svalbard reindeer (Rangifer tarandus platyrhynchus) is an endemic subspecies that colonized the Svalbard archipelago ca. 6,000–8,000 years ago and now shows numerous physiological and morphological adaptations to its arctic habitat. Here, we report a de-novo chromosome-level assembly for Svalbard reindeer and analyze 133 reindeer genomes spanning Svalbard and most of the species’ Holarctic range, to examine the genomic consequences of long-term isolation and small population size in this insular subspecies. Empirical data, demographic reconstructions, and forward simulations show that long-term isolation and high inbreeding levels may have facilitated the reduction of highly deleterious—and to a lesser extent, moderately deleterious—variation. Our study indicates that long-term reduced genetic diversity did not preclude local adaptation to the High Arctic, suggesting that even severely bottlenecked populations can retain evolutionary potential.
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6.
  • Escott-Price, Valentina, et al. (författare)
  • Gene-Wide Analysis Detects Two New Susceptibility Genes for Alzheimer's Disease
  • 2014
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:6, s. e94661-
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls. Principal Findings: In addition to earlier reported genes, we detected genome-wide significant loci on chromosomes 8 (TP53INP1, p = 1.4x10(-6)) and 14 (IGHV1-67 p = 7.9x10(-8)) which indexed novel susceptibility loci. Significance: The additional genes identified in this study, have an array of functions previously implicated in Alzheimer's disease, including aspects of energy metabolism, protein degradation and the immune system and add further weight to these pathways as potential therapeutic targets in Alzheimer's disease.
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  • Gratz, Regina, et al. (författare)
  • Organic nitrogen nutrition: LHT1.2 protein from hybrid aspen (Populus tremula L. x tremuloides Michx) is a functional amino acid transporter and a homolog of Arabidopsis LHT1
  • 2021
  • Ingår i: Tree Physiology. - : Oxford University Press (OUP). - 0829-318X .- 1758-4469. ; 41, s. 1479–1496-
  • Tidskriftsartikel (refereegranskat)abstract
    • The contribution of amino acids (AAs) to soil nitrogen (N) fluxes is higher than previously thought. The fact that AA uptake is pivotal for N nutrition in boreal ecosystems highlights plant AA transporters as key components of the N cycle. At the same time, very little is known about AA transport and respective transporters in trees. Tree genomes may contain 13 or more genes encoding the lysine histidine transporter (LHT) family proteins, and this complicates the study of their significance for tree N-use efficiency. With the strategy of obtaining a tool to study N-use efficiency, our aim was to identify and characterize a relevant AA transporter in hybrid aspen (Populus tremula L. x tremuloides Michx.). We identified PtrLHT1.2, the closest homolog of Arabidopsis thaliana (L.) Heynh AtLHT1, which is expressed in leaves, stems and roots. Complementation of a yeast AA uptake mutant verified the function of PtrLHT1.2 as an AA transporter. Furthermore, PtrLHT1.2 was able to fully complement the phenotypes of the Arabidopsis AA uptake mutant lht1 aap5, including early leaf senescence-like phenotype, reduced growth, decreased plant N levels and reduced root AA uptake. Amino acid uptake studies finally showed that PtrLHT1.2 is a high affinity transporter for neutral and acidic AAs. Thus, we identified a functional AtLHT1 homolog in hybrid aspen, which harbors the potential to enhance overall plant N levels and hence increase biomass production. This finding provides a valuable tool for N nutrition studies in trees and opens new avenues to optimizing tree N-use efficiency.
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8.
  • Guo, Qianqian, et al. (författare)
  • Depletion of carbohydrate reserves limits nitrate uptake during early regrowth in Lolium perenne L.
  • 2017
  • Ingår i: Journal of Experimental Botany. - : Oxford University Press. - 0022-0957 .- 1460-2431. ; 68:7, s. 1569-1583
  • Tidskriftsartikel (refereegranskat)abstract
    • The mechanisms linking C/N balance to N uptake and assimilation are central to plant responses to changing soil nutrient levels. Defoliation and subsequent regrowth of grasses both impact C partitioning, thereby creating a significant point of interaction with soil N availability. Using defoliation as an experimental treatment, we investigated the dynamic relationships between plant carbohydrate status and NO3--responsive uptake systems, transporter gene expression, and nitrate assimilation in Lolium perenne L. High- and low-affinity NO3- uptake was reduced in an N-dependent manner in response to a rapid and large shift in carbohydrate remobilization triggered by defoliation. This reduction in NO3- uptake was rescued by an exogenous glucose supplement, confirming the carbohydrate dependence of NO3- uptake. The regulation of NO3- uptake in response to the perturbation of the plant C/N ratio was associated with changes in expression of putative high- and low-affinity NO3- transporters. Furthermore, NO3- assimilation appears to be regulated by the C-N status of the plant, implying a mechanism that signals the availability of C metabolites for NO3- uptake and assimilation at the whole-plant level. We also show that cytokinins may be involved in the regulation of N acquisition and assimilation in response to the changing plant C/N ratio.
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  • Jones, Lesley, et al. (författare)
  • Convergent genetic and expression data implicate immunity in Alzheimer's disease
  • 2015
  • Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 11:6, s. 658-671
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Late-onset Alzheimer's disease (AD) is heritable with 20 genes showing genome-wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease, we extended these genetic data in a pathway analysis. Methods: The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain. Results: ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (P = 3.27 X 10(-12) after multiple testing correction for pathways), regulation of endocytosis (P = 1.31 X 10(-11)), cholesterol transport (P = 2.96 X 10(-9)), and proteasome-ubiquitin activity (P = 1.34 X 10(-6)). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected P = .002-.05). Conclusions: The immime response, regulation of endocytosis, cholesterol transport, and protein ubiquitination represent prime targets for AD therapeutics.
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