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4.
  • Schoch, CL, et al. (author)
  • Nuclear ribosomal internal transcribed spacer (ITS) region as a universal DNA barcode marker for Fungi
  • 2012
  • In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 109:16, s. 6241-6246
  • Journal article (peer-reviewed)abstract
    • Six DNA regions were evaluated as potential DNA barcodes for Fungi, the second largest kingdom of eukaryotic life, by a multinational, multilaboratory consortium. The region of the mitochondrial cytochrome c oxidase subunit 1 used as the animal barcode was excluded as a potential marker, because it is difficult to amplify in fungi, often includes large introns, and can be insufficiently variable. Three subunits from the nuclear ribosomal RNA cistron were compared together with regions of three representative protein-coding genes (largest subunit of RNA polymerase II, second largest subunit of RNA polymerase II, and minichromosome maintenance protein). Although the protein-coding gene regions often had a higher percent of correct identification compared with ribosomal markers, low PCR amplification and sequencing success eliminated them as candidates for a universal fungal barcode. Among the regions of the ribosomal cistron, the internal transcribed spacer (ITS) region has the highest probability of successful identification for the broadest range of fungi, with the most clearly defined barcode gap between inter- and intraspecific variation. The nuclear ribosomal large subunit, a popular phylogenetic marker in certain groups, had superior species resolution in some taxonomic groups, such as the early diverging lineages and the ascomycete yeasts, but was otherwise slightly inferior to the ITS. The nuclear ribosomal small subunit has poor species-level resolution in fungi. ITS will be formally proposed for adoption as the primary fungal barcode marker to the Consortium for the Barcode of Life, with the possibility that supplementary barcodes may be developed for particular narrowly circumscribed taxonomic groups.
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5.
  • Baron, J. S., et al. (author)
  • Synthesis Centers as Critical Research Infrastructure
  • 2017
  • In: Bioscience. - : Oxford University Press (OUP). - 0006-3568 .- 1525-3244. ; 67:8, s. 750-759
  • Journal article (peer-reviewed)abstract
    • Synthesis centers offer a unique amalgam of culture, infrastructure, leadership, and support that facilitates creative discovery on issues crucial to science and society. The combination of logistical support, postdoctoral or senior fellowships, complex data management, informatics and computing capability or expertise, and most of all, opportunity for group discussion and reflection lowers the "activation energy" necessary to promote creativity and the cross-fertilization of ideas. Synthesis centers are explicitly created and operated as community-oriented infrastructure, with scholarly directions driven by the ever-changing interests and needs of an open and inclusive scientific community. The last decade has seen a rise in the number of synthesis centers globally but also the end of core federal funding for several, challenging the sustainability of the infrastructure for this key research strategy. Here, we present the history and rationale for supporting synthesis centers, integrate insights arising from two decades of experience, and explore the challenges and opportunities for long-term sustainability.
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6.
  • Byrne, L. M., et al. (author)
  • Neurofilament light protein in blood as a potential biomarker of neurodegeneration in Huntington's disease: a retrospective cohort analysis
  • 2017
  • In: Lancet Neurology. - 1474-4422. ; 16:8, s. 601-609
  • Journal article (peer-reviewed)abstract
    • Background Blood biomarkers of neuronal damage could facilitate clinical management of and therapeutic development for Huntington's disease. We investigated whether neurofilament light protein NfL (also known as NF-L) in blood is a potential prognostic marker of neurodegeneration in patients with Huntington's disease. Methods We did a retrospective analysis of healthy controls and carriers of CAG expansion mutations in HTT participating in the 3-year international TRACK-HD study. We studied associations between NfL concentrations in plasma and clinical and MRI neuroimaging findings, namely cognitive function, motor function, and brain volume (global and regional). We used random effects models to analyse cross-sectional associations at each study visit and to assess changes from baseline, with and without adjustment for age and CAG repeat count. In an independent London-based cohort of 37 participants (23 HTT mutation carriers and 14 controls), we further assessed whether concentrations of NfL in plasma correlated with those in CSF. Findings Baseline and follow-up plasma samples were available from 97 controls and 201 individuals carrying HTT mutations. Mean concentrations of NfL in plasma at baseline were significantly higher in HTT mutation carriers than in controls (3.63 [SD 0.54] log pg/mL vs 2.68 [0.52] log pg/mL, p<0.0001) and the difference increased from one disease stage to the next. At any given timepoint, NfL concentrations in plasma correlated with clinical and MRI findings. In longitudinal analyses, baseline NfL concentration in plasma also correlated significantly with subsequent decline in cognition (symbol-digit modality test r=-0.374, p<0.0001; Stroop word reading r=-0.248, p=0.0033), total functional capacity (r=-0.289, p=0.0264), and brain atrophy (caudate r=0.178, p=0.0087; whole-brain r=0602, p<0.0001; grey matter r=0.518, p<00001; white matter r=0.588, p<0.0001; and ventricular expansion r=-0.589, p<0.0001). All changes except Stroop word reading and total functional capacity remained significant after adjustment for age and CAG repeat count. In 104 individuals with premanifest Huntington's disease, NfL concentration in plasma at baseline was associated with subsequent clinical onset during the 3-year follow-up period (hazard ratio 3.29 per log pg/mL, 95% CI 1.48-7.34, p=00036). Concentrations of NfL in CSF and plasma were correlated in mutation carriers (r=0868, p<0.0001). Interpretation NfL in plasma shows promise as a potential prognostic blood biomarker of disease onset and progression in Huntington's disease. Copyright (C) The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.
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7.
  • Costello, David M., et al. (author)
  • Global patterns and controls of nutrient immobilization on decomposing cellulose in riverine ecosystems
  • 2022
  • In: Global Biogeochemical Cycles. - : John Wiley & Sons. - 0886-6236 .- 1944-9224. ; 36:3
  • Journal article (peer-reviewed)abstract
    • Microbes play a critical role in plant litter decomposition and influence the fate of carbon in rivers and riparian zones. When decomposing low-nutrient plant litter, microbes acquire nitrogen (N) and phosphorus (P) from the environment (i.e., nutrient immobilization), and this process is potentially sensitive to nutrient loading and changing climate. Nonetheless, environmental controls on immobilization are poorly understood because rates are also influenced by plant litter chemistry, which is coupled to the same environmental factors. Here we used a standardized, low-nutrient organic matter substrate (cotton strips) to quantify nutrient immobilization at 100 paired stream and riparian sites representing 11 biomes worldwide. Immobilization rates varied by three orders of magnitude, were greater in rivers than riparian zones, and were strongly correlated to decomposition rates. In rivers, P immobilization rates were controlled by surface water phosphate concentrations, but N immobilization rates were not related to inorganic N. The N:P of immobilized nutrients was tightly constrained to a molar ratio of 10:1 despite wide variation in surface water N:P. Immobilization rates were temperature-dependent in riparian zones but not related to temperature in rivers. However, in rivers nutrient supply ultimately controlled whether microbes could achieve the maximum expected decomposition rate at a given temperature. Collectively, we demonstrated that exogenous nutrient supply and immobilization are critical control points for decomposition of organic matter.
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  • Jane, Stephen F., et al. (author)
  • Widespread deoxygenation of temperate lakes
  • 2021
  • In: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 594:7861, s. 66-70
  • Journal article (peer-reviewed)abstract
    • The concentration of dissolved oxygen in aquatic systems helps to regulate biodiversity(1,2), nutrient biogeochemistry(3), greenhouse gas emissions(4), and the quality of drinking water(5). The long-term declines in dissolved oxygen concentrations in coastal and ocean waters have been linked to climate warming and human activity(6,7), but little is known about the changes in dissolved oxygen concentrations in lakes. Although the solubility of dissolved oxygen decreases with increasing water temperatures, long-term lake trajectories are difficult to predict. Oxygen losses in warming lakes may be amplified by enhanced decomposition and stronger thermal stratification(8,9) or oxygen may increase as a result of enhanced primary production(10). Here we analyse a combined total of 45,148 dissolved oxygen and temperature profiles and calculate trends for 393 temperate lakes that span 1941 to 2017. We find that a decline in dissolved oxygen is widespread in surface and deep-water habitats. The decline in surface waters is primarily associated with reduced solubility under warmer water temperatures, although dissolved oxygen in surface waters increased in a subset of highly productive warming lakes, probably owing to increasing production of phytoplankton. By contrast, the decline in deep waters is associated with stronger thermal stratification and loss of water clarity, but not with changes in gas solubility. Our results suggest that climate change and declining water clarity have altered the physical and chemical environment of lakes. Declines in dissolved oxygen in freshwater are 2.75 to 9.3 times greater than observed in the world's oceans(6,7) and could threaten essential lake ecosystem services(2,3,5,11).
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10.
  • Tiegs, Scott D., et al. (author)
  • Global patterns and drivers of ecosystem functioning in rivers and riparian zones
  • 2019
  • In: Science Advances. - Washington : American Association of Advancement in Science. - 2375-2548. ; 5:1
  • Journal article (peer-reviewed)abstract
    • River ecosystems receive and process vast quantities of terrestrial organic carbon, the fate of which depends strongly on microbial activity. Variation in and controls of processing rates, however, are poorly characterized at the global scale. In response, we used a peer-sourced research network and a highly standardized carbon processing assay to conduct a global-scale field experiment in greater than 1000 river and riparian sites. We found that Earth's biomes have distinct carbon processing signatures. Slow processing is evident across latitudes, whereas rapid rates are restricted to lower latitudes. Both the mean rate and variability decline with latitude, suggesting temperature constraints toward the poles and greater roles for other environmental drivers (e.g., nutrient loading) toward the equator. These results and data set the stage for unprecedented "next-generation biomonitoring" by establishing baselines to help quantify environmental impacts to the functioning of ecosystems at a global scale.
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11.
  • Van Raamsdonk, Jeremy M., et al. (author)
  • Testicular degeneration in Huntington disease
  • 2007
  • In: Neurobiology of Disease. - : Elsevier BV. - 0969-9961. ; 26:3, s. 512-520
  • Journal article (peer-reviewed)abstract
    • Huntington disease (HD) is an adult onset, neurodegenerative disorder that results from CAG expansion in the HD gene. Recent work has demonstrated testicular degeneration in mouse models of HD and alterations in the hypothalamic-pituitary-gonadal (HPG) axis in HD patients. Here, we show that HD patients have specific testicular pathology with reduced numbers of germ cells and abnormal seminiferous tubule morphology. In the YAC128 mouse model, testicular degeneration develops prior to 12 months of age, but at 12 months, there is no evidence for decreased testosterone levels or loss of GnRH neurons in the hypothalamus. This suggests that testicular pathology results from a direct toxic effect of mutant huntingtin in the testis and is supported by the fact that huntingtin is highly expressed in the affected cell populations in the testis. Understanding the pathogenesis of HD in the testis may reveal common critical pathways which lead to degeneration in both the brain and testis.
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  • Björkqvist, Maria, et al. (author)
  • A novel pathogenic pathway of immune activation detectable before clinical onset in Huntington's disease.
  • 2008
  • In: Journal of Experimental Medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 205, s. 1869-1877
  • Journal article (peer-reviewed)abstract
    • Huntington's disease (HD) is an inherited neurodegenerative disorder characterized by both neurological and systemic abnormalities. We examined the peripheral immune system and found widespread evidence of innate immune activation detectable in plasma throughout the course of HD. Interleukin 6 levels were increased in HD gene carriers with a mean of 16 years before the predicted onset of clinical symptoms. To our knowledge, this is the earliest plasma abnormality identified in HD. Monocytes from HD subjects expressed mutant huntingtin and were pathologically hyperactive in response to stimulation, suggesting that the mutant protein triggers a cell-autonomous immune activation. A similar pattern was seen in macrophages and microglia from HD mouse models, and the cerebrospinal fluid and striatum of HD patients exhibited abnormal immune activation, suggesting that immune dysfunction plays a role in brain pathology. Collectively, our data suggest parallel central nervous system and peripheral pathogenic pathways of immune activation in HD.
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  • Connolly, C, et al. (author)
  • Enhanced immune response to MMP3 stimulation in microglia expressing mutant huntingtin
  • 2016
  • In: Neuroscience. - : Elsevier BV. - 1873-7544 .- 0306-4522. ; 325, s. 74-88
  • Journal article (peer-reviewed)abstract
    • Huntington's Disease (HD) is an inherited neurodegenerative disease caused by a polyglutamine expansion in the huntingtin protein. The YAC128 mouse model of HD expresses the full-length human huntingtin protein with 128 CAG repeats and replicates the phenotype and neurodegeneration that occur in HD. Several studies have implicated a role for neuroinflammation in HD pathogenesis. Studies on presymptomatic HD patients have illustrated microgliosis (activated microglia) in brain regions affected in HD. Mutant huntingtin expressing isolated primary monocytes (human HD patients) and primary macrophages (YAC128) are overactive in response to lipopolysaccharide (LPS) stimulation. In this study we demonstrate that cultured primary microglia (the resident immune cells of the brain cells) from YAC128 mice differentially express a wide number of cytokines compared to wildtype microglia cultures in response to LPS. Furthermore, this study outlines a direct interaction between mutant huntingtin and cytokine secretion in HD microglia. Increased cytokine release in YAC128 microglia can be blocked by cannabinoid activation or by mutant huntingtin knockdown with anti-sense oligonucleotide treatment. Matrix metalloprotease 3 (MMP3), an endogenous neuronal activator of microglia, also induces increased cytokine release from YAC128 microglia compared to wildtype microglia. We found elevated MMP levels in HD CSF, and MMP levels correlate with disease severity in HD. These data support a novel role for MMPs and microglial activation in HD pathogenesis. With an improved understanding of the specific cellular processes involved in HD neuroinflammation, novel therapeutic agents targeting these processes can be developed and hold great promise in the treatment of HD.
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  • Kraemer, Benjamin M., et al. (author)
  • Climate change drives widespread shifts in lake thermal habitat
  • 2021
  • In: Nature Climate Change. - : Springer Science and Business Media LLC. - 1758-678X .- 1758-6798. ; 11:6, s. 521-529
  • Journal article (peer-reviewed)abstract
    • Lake surfaces are warming worldwide, raising concerns about lake organism responses to thermal habitat changes. Species may cope with temperature increases by shifting their seasonality or their depth to track suitable thermal habitats, but these responses may be constrained by ecological interactions, life histories or limiting resources. Here we use 32 million temperature measurements from 139 lakes to quantify thermal habitat change (percentage of non-overlap) and assess how this change is exacerbated by potential habitat constraints. Long-term temperature change resulted in an average 6.2% non-overlap between thermal habitats in baseline (1978-1995) and recent (1996-2013) time periods, with non-overlap increasing to 19.4% on average when habitats were restricted by season and depth. Tropical lakes exhibited substantially higher thermal non-overlap compared with lakes at other latitudes. Lakes with high thermal habitat change coincided with those having numerous endemic species, suggesting that conservation actions should consider thermal habitat change to preserve lake biodiversity. Using measurements from 139 global lakes, the authors demonstrate how long-term thermal habitat change in lakes is exacerbated by species' seasonal and depth-related constraints. They further reveal higher change in tropical lakes, and those with high biodiversity and endemism.
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  • Pilla, Rachel M., et al. (author)
  • Global data set of long-term summertime vertical temperature profiles in 153 lakes
  • 2021
  • In: Scientific Data. - : Springer Nature. - 2052-4463. ; 8:1
  • Journal article (peer-reviewed)abstract
    • Climate change and other anthropogenic stressors have led to long-term changes in the thermal structure, including surface temperatures, deepwater temperatures, and vertical thermal gradients, in many lakes around the world. Though many studies highlight warming of surface water temperatures in lakes worldwide, less is known about long-term trends in full vertical thermal structure and deepwater temperatures, which have been changing less consistently in both direction and magnitude. Here, we present a globally-expansive data set of summertime in-situ vertical temperature profiles from 153 lakes, with one time series beginning as early as 1894. We also compiled lake geographic, morphometric, and water quality variables that can influence vertical thermal structure through a variety of potential mechanisms in these lakes. These long-term time series of vertical temperature profiles and corresponding lake characteristics serve as valuable data to help understand changes and drivers of lake thermal structure in a time of rapid global and ecological change.
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  • Schoch, Conrad L., et al. (author)
  • Finding needles in haystacks: linking scientific names, reference specimens and molecular data for Fungi
  • 2014
  • In: Database: The Journal of Biological Databases and Curation. - : Oxford University Press (OUP). - 1758-0463. ; 2014:bau061, s. 1-21
  • Journal article (peer-reviewed)abstract
    • DNA phylogenetic comparisons have shown that morphology-based species recognition often underestimates fungal diversity. Therefore, the need for accurate DNA sequence data, tied to both correct taxonomic names and clearly annotated specimen data, has never been greater. Furthermore, the growing number of molecular ecology and microbiome projects using high-throughput sequencing require fast and effective methods for en masse species assignments. In this article, we focus on selecting and re-annotating a set of marker reference sequences that represent each currently accepted order of Fungi. The particular focus is on sequences from the internal transcribed spacer region in the nuclear ribosomal cistron, derived from type specimens and/or ex-type cultures. Re-annotated and verified sequences were deposited in a curated public database at the National Center for Biotechnology Information (NCBI), namely the RefSeq Targeted Loci (RTL) database, and will be visible during routine sequence similarity searches with NR_prefixed accession numbers. A set of standards and protocols is proposed to improve the data quality of new sequences, and we suggest how type and other reference sequences can be used to improve identification of Fungi.
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  • Träger, Ulrike, et al. (author)
  • Characterisation of immune cell function in fragment and full-length Huntington's disease mouse models.
  • 2015
  • In: Neurobiology of Disease. - : Elsevier BV. - 0969-9961. ; 73, s. 388-398
  • Journal article (peer-reviewed)abstract
    • Inflammation is a growing area of research in neurodegeneration. In Huntington's disease (HD), a fatal inherited neurodegenerative disease caused by a CAG-repeat expansion in the gene encoding huntingtin, patients have increased plasma levels of inflammatory cytokines and circulating monocytes that are hyper-responsive to immune stimuli. Several mouse models of HD also show elevated plasma levels of inflammatory cytokines. To further determine the degree to which these models recapitulate observations in HD patients, we evaluated various myeloid cell populations from different HD mouse models to determine whether they are similarly hyper-responsive, as well as measuring other aspects of myeloid cell function. Myeloid cells from each of the three mouse models studied, R6/2, HdhQ150 knock-in and YAC128, showed increased cytokine production when stimulated. However, bone marrow CD11b(+) cells did not show the same hyper-responsive phenotype as spleen and blood cells. Furthermore, macrophages isolated from R6/2 mice show increased levels of phagocytosis, similar to findings in HD patients. Taken together, these results show significant promise for these mouse models to be used to study targeting innate immune pathways identified in human cells, thereby helping to understand the role the peripheral immune system plays in HD progression.
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18.
  • Wild, Edward J, et al. (author)
  • Quantification of mutant huntingtin protein in cerebrospinal fluid from Huntington's disease patients.
  • 2015
  • In: The Journal of clinical investigation. - 1558-8238. ; 125:5, s. 1979-1986
  • Journal article (peer-reviewed)abstract
    • Quantification of disease-associated proteins in the cerebrospinal fluid (CSF) has been critical for the study and treatment of several neurodegenerative disorders; however, mutant huntingtin protein (mHTT), the cause of Huntington's disease (HD), is at very low levels in CSF and, to our knowledge, has never been measured previously.
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  • Zeron, Melinda M, et al. (author)
  • Increased Sensitivity to N-Methyl-D-Aspartate Receptor-Mediated Excitotoxicity in a Mouse Model of Huntington's Disease.
  • 2002
  • In: Neuron. - 0896-6273. ; 33:6, s. 849-860
  • Journal article (peer-reviewed)abstract
    • Previous work suggests N-methyl-D-aspartate receptor (NMDAR) activation may be involved in degeneration of medium-sized spiny striatal neurons in Huntington's disease (HD). Here we show that these neurons are more vulnerable to NMDAR-mediated death in a YAC transgenic FVB/N mouse model of HD expressing full-length mutant huntingtin, compared with wild-type FVB/N mice. Excitotoxic death of these neurons was increased after intrastriatal injection of quinolinate in vivo, and after NMDA but not AMPA exposure in culture. NMDA-induced cell death was abolished by an NR2B subtype-specific antagonist. In contrast, NMDAR-mediated death of cerebellar granule neurons was not enhanced, consistent with cell-type and NMDAR subtype specificity. Moreover, increased NMDA-evoked current amplitude and caspase-3 activity were observed in transgenic striatal neurons. Our data support a role for NR2B-subtype NMDAR activation as a trigger for selective neuronal degeneration in HD.
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  • Bauer, D W, et al. (author)
  • Exploring the balance between DNA pressure and capsid stability in Herpes and phage.
  • 2015
  • In: Journal of Virology. - 1098-5514. ; 89:18, s. 9288-9298
  • Journal article (peer-reviewed)abstract
    • We have recently shown in both herpesviruses and phages that packaged viral DNA creates a pressure of tens of atmospheres pushing against the interior capsid wall. For the first time, using differential scanning microcalorimetry, we directly measure the energy powering the release of pressurized DNA from the capsid. Furthermore, using a new calorimetric assay to accurately determine the temperature inducing DNA release, we found a direct influence of internal DNA pressure on the stability of the viral particle. We show that the balance of forces between the DNA pressure and capsid strength, required for DNA retention between rounds of infection, is conserved between evolutionarily diverse bacterial viruses (phage λ and P22), as well as a eukaryotic virus, human Herpes Simplex 1 (HSV-1). Our data also suggest that the portal vertex in these viruses is the weakest point in the overall capsid structure and presents the "Achilles' heel" of virus's stability. Comparison between these viral systems shows that viruses with higher DNA packing density (resulting in higher capsid pressure) have inherently stronger capsid structures preventing spontaneous genome release prior to infection. This force balance is of key importance for viral survival and replication. Investigating the ways to disrupt this balance can lead to development of new mutation resistant anti-virals.
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  • Catalan, Jordi, et al. (author)
  • Global change revealed by palaeolimnological records from remote lakes : a review
  • 2013
  • In: Journal of Paleolimnology. - : Springer Netherlands. - 0921-2728 .- 1573-0417. ; 49:3, s. 513-535
  • Journal article (peer-reviewed)abstract
    • Over recent decades, palaeolimnological records from remote sites have provided convincing evidence for the onset and development of several facets of global environmental change. Remote lakes, defined here as those occurring in high latitude or high altitude regions, have the advantage of not being overprinted by local anthropogenic processes. As such, many of these sites record broad-scale environmental changes, frequently driven by regime shifts in the Earth system. Here, we review a selection of studies from North America and Europe and discuss their broader implications. The history of investigation has evolved synchronously with the scope and awareness of environmental problems. An initial focus on acid deposition switched to metal and other types of pollutants, then climate change and eventually to atmospheric deposition-fertilising effects. However, none of these topics is independent of the other, and all of them affect ecosystem function and biodiversity in profound ways. Currently, remote lake palaeolimnology is developing unique datasets for each region investigated that benchmark current trends with respect to past, purely natural variability in lake systems. Fostering conceptual and methodological bridges with other environmental disciplines will upturn contribution of remote lake palaeolimnology in solving existing and emerging questions in global change science and planetary stewardship.
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24.
  • Dalrymple, Annette, et al. (author)
  • Proteomic profiling of plasma in Huntington's disease reveals neuroinflammatory activation and biomarker candidates
  • 2007
  • In: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 6:7, s. 2833-2840
  • Journal article (peer-reviewed)abstract
    • Huntington's disease (HD) causes widespread CNS changes and systemic abnormalities including endocrine and immune dysfunction. HD biomarkers are needed to power clinical trials of potential treatments. We used multiplatform proteomic profiling to reveal plasma changes with HD progression. Proteins of interest were evaluated using immunoblotting and ELISA in plasma from 2 populations, CSF and R6/2 mice. The identified proteins demonstrate neuroinflammation in HD and warrant further investigation as possible biomarkers.
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  • Holtgrieve, Gordon W., et al. (author)
  • A Coherent Signature of Anthropogenic Nitrogen Deposition to Remote Watersheds of the Northern Hemisphere
  • 2011
  • In: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 334:6062, s. 1545-1548
  • Journal article (peer-reviewed)abstract
    • Humans have more than doubled the amount of reactive nitrogen (Nr) added to the biosphere, yet most of what is known about its accumulation and ecological effects is derived from studies of heavily populated regions. Nitrogen (N) stable isotope ratios (N-15:N-14) in dated sediments from 25 remote Northern Hemisphere lakes show a coherent signal of an isotopically distinct source of N to ecosystems beginning in 1895 +/- 10 years (+/- 1 standard deviation). Initial shifts in N isotope composition recorded in lake sediments coincide with anthropogenic CO2 emissions but accelerate with widespread industrial Nr production during the past half century. Although current atmospheric Nr deposition rates in remote regions are relatively low, anthropogenic N has probably influenced watershed N budgets across the Northern Hemisphere for over a century.
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26.
  • Johnson, Eileanoir B, et al. (author)
  • Neurofilament light protein in blood predicts regional atrophy in Huntington disease.
  • 2018
  • In: Neurology. - 1526-632X. ; 90:8
  • Journal article (peer-reviewed)abstract
    • Neurofilament light (NfL) protein in blood plasma has been proposed as a prognostic biomarker of neurodegeneration in a number of conditions, including Huntington disease (HD). This study investigates the regional distribution of NfL-associated neural pathology in HD gene expansion carriers.We examined associations between NfL measured in plasma and regionally specific atrophy in cross-sectional (n = 198) and longitudinal (n = 177) data in HD gene expansion carriers from the international multisite TRACK-HD study. Using voxel-based morphometry, we measured associations between baseline NfL levels and both baseline gray matter and white matter volume; and longitudinal change in gray matter and white matter over the subsequent 3 years in HD gene expansion carriers.After controlling for demographics, associations between increased NfL levels and reduced brain volume were seen in cortical and subcortical gray matter and within the white matter. After also controlling for known predictors of disease progression (age and CAG repeat length), associations were limited to the caudate and putamen. Longitudinally, NfL predicted subsequent occipital gray matter atrophy and widespread white matter reduction, both before and after correction for other predictors of disease progression.These findings highlight the value of NfL as a dynamic marker of brain atrophy and, more generally, provide further evidence of the strong association between plasma NfL level, a candidate blood biomarker, and pathologic neuronal change.
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29.
  • Leavitt, Peter R., et al. (author)
  • Paleolimnological evidence of the effects on lakes of energy and mass transfer from climate and humans
  • 2009
  • In: Limnology and Oceanography. - 0024-3590 .- 1939-5590. ; 54:6, s. 2330-2348
  • Research review (peer-reviewed)abstract
    • The premise of this article is that climate effects on lakes can be quantified most effectively by the integration of process-oriented limnological studies with paleolimnological research, particularly when both disciplines operate within a common conceptual framework. To this end, the energy (E)-mass (m) flux framework (Em flux) is developed and applied to selected retrospective studies to demonstrate that climate variability regulates lake structure and function over diverse temporal and spatial scales through four main pathways: rapid direct transfer of E to the lake surface by irradiance, heat, and wind; slow indirect effects of E via changes in terrestrial development and subsequent m subsidies to lakes; direct influx of m as precipitation, particles, and solutes from the atmosphere; and indirect influx of water, suspended particles, and dissolved substances from the catchment. Sedimentary analyses are used to illustrate the unique effects of each pathway on lakes but suggest that interactions among mechanisms are complex and depend on the landscape position of lakes, catchment characteristics, the range of temporal variation of individual pathways, ontogenetic changes in lake basins, and the selective effects of humans on m transfers. In particular, preliminary synthesis suggests that m influx can overwhelm the direct effects of E transfer to lakes, especially when anthropogenic activities alter m subsidies from catchments.
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31.
  • Liu, Y., et al. (author)
  • Anthropogenic Aerosols Cause Recent Pronounced Weakening of Asian Summer Monsoon Relative to Last Four Centuries
  • 2019
  • In: Geophysical Research Letters. - : American Geophysical Union (AGU). - 0094-8276 .- 1944-8007. ; 46:10, s. 5469-5479
  • Journal article (peer-reviewed)abstract
    • The Asian Summer Monsoon (ASM) affects ecosystems, biodiversity, and food security of billions of people. In recent decades, ASM strength (as represented by precipitation) has been decreasing, but instrumental measurements span only a short period of time. The initiation and the dynamics of the recent trend are unclear. Here for the first time, we use an ensemble of 10 tree ring-width chronologies from the west-central margin of ASM to reconstruct detail of ASM variability back to 1566 CE. The reconstruction captures weak/strong ASM events and also reflects major locust plagues. Notably, we found an unprecedented 80-year trend of decreasing ASM strength within the context of the 448-year reconstruction, which is contrary to what is expected from greenhouse warming. Our coupled climate model shows that increasing anthropogenic sulfate aerosol emissions over the Northern Hemisphere could be the dominant factor contributing to the ASM decrease. Plan Language Summary Monsoonal rainfall has a certain influence on agriculture and industry in the regions of Asian Summer Monsoon (ASM). An understanding of the spatial-temporal variability of the ASM and the associated dynamics is vital for terrestrial ecosystems, water resources, forests, and landscapes. We have developed a 448-year ASM reconstruction back to 1566 CE using 10 tree ring chronologies from the margin region of ASM. We find that historical severe droughts and locust plague disasters during weak ASM events. The recent decreasing ASM trend persisting for over 80 years is unprecedented over the past 448 years. Coupled climate models show that increasing anthropogenic aerosol emissions are the dominant underlying factor. Our aim is that the time series will find a wide range of utility for understanding past climate variability and for predicting future climate change.
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  • Liu, Yu, et al. (author)
  • Individual and pooled tree-ring stable-carbon isotope series in Chinese pine from the Nan Wutai region, China: Common signal and climate relationships
  • 2012
  • In: Chemical Geology. - : Elsevier BV. - 0009-2541. ; 330-331, s. 17-26
  • Journal article (peer-reviewed)abstract
    • To investigate the differences in the climatic signals in stable-carbon isotopic composition captured by averaging series from individual trees versus raw wood of trees pooled prior to analysis, we analyzed two groups of Chinese pine (Pinus tabulaeformis Carr.) from the Nan Wutai region of the Qinling Mountains, China. One group included three trees that were analyzed separately, and the other group comprised four other trees that were pooled prior to preparation and analysis. All δ13C series were positively correlated (r= 0.50–0.58, pb0.0001) for the period AD 1901–2003. After removing the effects of changing δ13C of atmospheric CO2, correlations between the meteorological data and all individual and pooled discrimination (Δ13C) series revealed significant negative responses to temperature for several specific months and for mean January to September (TJ–S) temperature. We used a “numerical mix method” (NMM, equivalent to unweighted mean), by averaging individual Δ13C series (NPS1+NPS2+NPS3), to generate a new series that more strongly correlated to climate series TJ–S (r=−0.67, pb0.0001). This time interval from January through September (J–S) includes the growing season and months prior to the growing season, but the temperature prior to the growing season may provide energy necessary for timely initiation of growth. Thus, the mean TJ–S is significant for plant growth and is consistent with the tree physiology in this region. Our results suggest that the numerical mix method with tree-ring stable isotope data from three trees provides a series quite satisfactory for climatic reconstruction. The relationship of the numerical mix model Δ13C with temperature was stronger than for the pooled series, suggesting numerical mixing of series can be more effective than raw wood sample pooling at least according to the trees in this study.
  •  
33.
  • Liu, Y., et al. (author)
  • Recent enhancement of central Pacific El Nino variability relative to last eight centuries
  • 2017
  • In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
  • Journal article (peer-reviewed)abstract
    • The far-reaching impacts of central Pacific El Nino events on global climate differ appreciably from those associated with eastern Pacific El Nino events. Central Pacific El Nino events may become more frequent in coming decades as atmospheric greenhouse gas concentrations rise, but the instrumental record of central Pacific sea-surface temperatures is too short to detect potential trends. Here we present an annually resolved reconstruction of NINO4 sea-surface temperature, located in the central equatorial Pacific, based on oxygen isotopic time series from Taiwan tree cellulose that span from 1190 AD to 2007 AD. Our reconstruction indicates that relatively warm Nino4 sea-surface temperature values over the late twentieth century are accompanied by higher levels of interannual variability than observed in other intervals of the 818-year-long reconstruction. Our results imply that anthropogenic greenhouse forcing may be driving an increase in central Pacific El Nino-Southern Oscillation variability and/or its hydrological impacts, consistent with recent modelling studies.
  •  
34.
  • Pilla, Rachel M., et al. (author)
  • Deeper waters are changing less consistently than surface waters in a global analysis of 102 lakes
  • 2020
  • In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
  • Journal article (peer-reviewed)abstract
    • Globally, lake surface water temperatures have warmed rapidly relative to air temperatures, but changes in deepwater temperatures and vertical thermal structure are still largely unknown. We have compiled the most comprehensive data set to date of long-term (1970–2009) summertime vertical temperature profiles in lakes across the world to examine trends and drivers of whole-lake vertical thermal structure. We found significant increases in surface water temperatures across lakes at an average rate of + 0.37 °C decade−1, comparable to changes reported previously for other lakes, and similarly consistent trends of increasing water column stability (+ 0.08 kg m−3 decade−1). In contrast, however, deepwater temperature trends showed little change on average (+ 0.06 °C decade−1), but had high variability across lakes, with trends in individual lakes ranging from − 0.68 °C decade−1 to + 0.65 °C decade−1. The variability in deepwater temperature trends was not explained by trends in either surface water temperatures or thermal stability within lakes, and only 8.4% was explained by lake thermal region or local lake characteristics in a random forest analysis. These findings suggest that external drivers beyond our tested lake characteristics are important in explaining long-term trends in thermal structure, such as local to regional climate patterns or additional external anthropogenic influences.
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35.
  • Reuss, Nina, et al. (author)
  • Development and application of sedimentary pigments for assessing effects of climatic and environmental changes on subarctic lakes in northern Sweden
  • 2010
  • In: Journal of Paleolimnology. - : Springer Science and Business Media LLC. - 0921-2728 .- 1573-0417. ; 43:1, s. 149-169
  • Journal article (peer-reviewed)abstract
    • A surface-sediment survey of pigments in 100 lakes in the Scandes Mountains, northern Sweden, was combined with a reconstruction of Holocene sedimentary pigments from Lake Seukokjaure to assess the major factors regulating phototrophic communities, and how these controls may have changed during the period from the deglaciation (similar to 9700 cal. years BP) to the present. The study area covers a pronounced gradient of temperature and precipitation, and encompasses the subarctic tree line, an important ecotonal boundary in this region. Lake Seukokjaure is located in a presently treeless basin close to the modern tree line. The spatial survey of sedimentary pigments was analyzed using principle components analysis (PCA) and redundancy analysis (RDA). PCA explained 73-83% of variance in pigment abundance and composition, whereas RDA explained 22-32% of variation in fossil assemblages. Dissolved organic carbon (DOC) content of lake water, sediment delta C-13, maximum lake depth, elevation and lake-water conductivity were all identified as environmental variables with significant association with pigment abundances in the spatial survey, although phototrophic communities of lakes situated in different vegetation zones (alpine, birch, conifer/birch) were incompletely distinguished by the ordinations. In the RDAs, the primary pigment variability occurred along a production gradient that was correlated negatively to water-column DOC content and delta C-13 signature of sediments. This pattern suggested that the important controls of primary production were light regime and terrestrial supplies of C-13-depleted carbon. In contrast, depth, elevation and conductivity were found to be more important for the differentiation of the phototrophic community composition. Application of these spatial survey results to the Holocene sediment record of Lake Seukokjaure demonstrated the importance of DOC for the temporal development of the lake, from an early state of high production to a period of slight oligotrophication. In general, the algal changes were regulated by the interaction of DOC and conductivity, although transitions in the phototrophic community during the late Holocene were less easily interpreted. Terrestrial vegetation development thus appears to be of utmost importance for the regulation of primary production in oligotrophic alpine and subarctic lakes and climate impacts on lakes, whereas other basin-specific factors may control the ontogeny of algal community composition.
  •  
36.
  • Rodrigues, F. B., et al. (author)
  • Cerebrospinal fluid total tau concentration predicts clinical phenotype in Huntington's disease
  • 2016
  • In: Journal of Neurochemistry. - : Wiley. - 0022-3042. ; 139:1, s. 22-25
  • Journal article (peer-reviewed)abstract
    • Huntington's disease (HD) is a hereditary neurodegenerative condition with no therapeutic intervention known to alter disease progression, but several trials are ongoing and biomarkers of disease progression are needed. Tau is an axonal protein, often altered in neurodegeneration, and recent studies pointed out its role on HD neuropathology. Our goal was to study whether cerebrospinal fluid (CSF) tau is a biomarker of disease progression in HD. After informed consent, healthy controls, pre-symptomatic and symptomatic gene expansion carriers were recruited from two HD clinics. All participants underwent assessment with the Unified HD Rating Scale ’99 (UHDRS). CSF was obtained according to a standardized lumbar puncture protocol. CSF tau was quantified using enzyme-linked immunosorbent assay. Comparisons between two groups were tested using ancova. Pearson's correlation coefficients were calculated for disease progression. Significance level was defined as p<0.05. Seventy-six participants were included in this cross-sectional multicenter international pilot study. Age-adjusted CSF tau was significantly elevated in gene expansion carriers compared with healthy controls (p=0.002). UHDRS total functional capacity was significantly correlated with CSF tau (r=−0.29, p=0.004) after adjustment for age, and UHDRS total motor score was significantly correlated with CSF tau after adjustment for age (r=0.32, p=0.002). Several UHDRS cognitive tasks were also significantly correlated with CST total tau after age-adjustment. This study confirms that CSF tau concentrations in HD gene mutation carriers are increased compared with healthy controls and reports for the first time that CSF tau concentration is associated with phenotypic variability in HD. These conclusions strengthen the case for CSF tau as a biomarker in HD. (Figure presented.) In the era of novel targeted approaches to Huntington's disease, reliable biomarkers are needed. We quantified Tau protein, a marker of neuronal death, in cerebrospinal fluid and found it was increased in patients with Huntington's disease and predicted motor, cognitive, and functional disability in patients. It is therefore likely to be a biomarker of disease progression, and possibly of therapeutic response. Read the Editorial Highlight for this article on page 9. © 2016 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry
  •  
37.
  • Savage, Candida, et al. (author)
  • Effects of land use, urbanization, and climate variability on coastal eutrophication in the Baltic Sea
  • 2010
  • In: Limnology and Oceanography. - : Wiley. - 0024-3590 .- 1939-5590. ; 55:3, s. 1033-1046
  • Journal article (peer-reviewed)abstract
    • Sedimentary records of organic matter inputs (stable nitrogen isotopes [delta N-15], nitrogen [N], and carbon [C] content), phytoplankton abundance (pigments, stable carbon isotopes [delta C-13]), and community composition (pigments) were used to reconstruct the history and pathway to water-quality degradation in a Swedish Baltic coastal bay. Changes in nutrient sources and cycling began in the 1800s, but eutrophication intensified only after the 1950s, coincident with intensified agricultural practices. Specifically, sedimentary N and C content doubled, delta 13C increased, and concentrations of pigments indicative of total algal biomass (beta-carotene, Chlorophyll a), diatoms (fucoxanthin, diatoxanthin), chlorophytes (lutein-zeaxanthin, Chlorophyll b), and cyanobacteria (canthaxanthin) increased significantly after 1950. Enhanced algal abundance was most strongly related to total N influx and secondly to total P influx. In particular, historical change in algae was related to agricultural N influx and only weakly to agricultural P. In recent decades, wastewater N influx has further stimulated algal biomass, particularly diatoms. In contrast, colonial cyanobacteria were more correlated to total P than total N inputs. Variance-partitioning analysis explained 60% of the changes in algal abundance and community composition since 1880, with diffuse and point nutrients jointly explaining 36% of the long-term change in algal biomass. Climate variability has become more important as a factor influencing coastal eutrophication in recent decades, explaining 14% of the variance in the algal data since 1975. Both urban and agricultural sources of nutrients have degraded water quality, illustrating the need for cooperation between stakeholders at regional levels to achieve ""good ecological status'' in the Baltic coastal environment.
  •  
38.
  • Thell, Arne, et al. (author)
  • A review of the lichen family Parmeliaceae - history, phylogeny and current taxonomy.
  • 2012
  • In: Nordic Journal of Botany. - : Wiley. - 0107-055X. ; 30:6, s. 641-664
  • Journal article (peer-reviewed)abstract
    • The largest family of lichen-forming fungi, the Parmeliaceae, is reviewed. It includes 79 genera in current use and ca 2726 species, a large majority of which belong to one of five main clades: the parmelioid, cetrarioid, usneoid, alectorioid and hypogymnioid. However, 21 genera are positioned outside these clades, and four genera in current use still lack DNA- data. The family has been shown to be monophyletic and the generic classification is relatively well-settled compared with other lecanoralean families. Each clade and its genera are presented here with the latest results from phylogenetic analyses and current taxonomy. In addition, a historical outline of the family and its most prominent researchers is provided.
  •  
39.
  • Tierney, Warren, et al. (author)
  • Creative destruction in science
  • 2020
  • In: Organizational Behavior and Human Decision Processes. - : Elsevier BV. - 0749-5978 .- 1095-9920. ; 161, s. 291-309
  • Journal article (peer-reviewed)abstract
    • Drawing on the concept of a gale of creative destruction in a capitalistic economy, we argue that initiatives to assess the robustness of findings in the organizational literature should aim to simultaneously test competing ideas operating in the same theoretical space. In other words, replication efforts should seek not just to support or question the original findings, but also to replace them with revised, stronger theories with greater explanatory power. Achieving this will typically require adding new measures, conditions, and subject populations to research designs, in order to carry out conceptual tests of multiple theories in addition to directly replicating the original findings. To illustrate the value of the creative destruction approach for theory pruning in organizational scholarship, we describe recent replication initiatives re-examining culture and work morality, working parents’ reasoning about day care options, and gender discrimination in hiring decisions.Significance statementIt is becoming increasingly clear that many, if not most, published research findings across scientific fields are not readily replicable when the same method is repeated. Although extremely valuable, failed replications risk leaving a theoretical void — reducing confidence the original theoretical prediction is true, but not replacing it with positive evidence in favor of an alternative theory. We introduce the creative destruction approach to replication, which combines theory pruning methods from the field of management with emerging best practices from the open science movement, with the aim of making replications as generative as possible. In effect, we advocate for a Replication 2.0 movement in which the goal shifts from checking on the reliability of past findings to actively engaging in competitive theory testing and theory building.Scientific transparency statementThe materials, code, and data for this article are posted publicly on the Open Science Framework, with links provided in the article.
  •  
40.
  • Wagner, Leona, et al. (author)
  • Proteolytic degradation of neuropeptide Y (NPY) from head to toe: Identification of novel NPY-cleaving peptidases and potential drug interactions in CNS and Periphery.
  • 2015
  • In: Journal of Neurochemistry. - : Wiley. - 1471-4159 .- 0022-3042. ; 135:5, s. 1019-1037
  • Journal article (peer-reviewed)abstract
    • The bioactivity of neuropeptide Y (NPY) is either N-terminally modulated with respect to receptor-selectivity by dipeptidyl-peptidase 4 (DP4)-like enzymes or proteolytic degraded by neprilysin or meprins, thereby abrogating signal transduction. However, neither the subcellular nor the compartmental differentiation of these regulatory mechanisms is fully understood. Using mass spectrometry, selective inhibitors and histochemistry, studies across various cell types, body fluids and tissues revealed that most frequently DP4-like enzymes, aminopeptidases P (AmpP), secreted meprin-A (Mep-A) and cathepsin D (CTSD) rapidly hydrolyze NPY, depending on the cell type and tissue under study. Novel degradation of NPY by cathepsins B, D, L, G, S and tissue kallikrein could also be identified. Expression of DP4, CTSD, and Mep-A at the median eminence indicates that the bioactivity of NPY is regulated by peptidases at the interphase between the periphery and the CNS. Detailed ex vivo studies on human sera and CSF samples recognized CTSD as the major NPY-cleaving enzyme in the CSF, whereas an additional C-terminal truncation by angiotensin-converting enzyme (ACE) could be detected in serum. The latter finding hints to potential drug interaction between antidiabetic DP4 inhibitors and anti-hypertensive ACE inhibitors, while it ablates suspected hypertensive side-effects of only antidiabetic DP4-inhibitors application. This article is protected by copyright. All rights reserved.
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