| 1. |
- Fenstermacher, M.E., et al.
(author)
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DIII-D research advancing the physics basis for optimizing the tokamak approach to fusion energy
- 2022
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In: Nuclear Fusion. - : IOP Publishing. - 0029-5515 .- 1741-4326. ; 62:4
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Journal article (peer-reviewed)abstract
- DIII-D physics research addresses critical challenges for the operation of ITER and the next generation of fusion energy devices. This is done through a focus on innovations to provide solutions for high performance long pulse operation, coupled with fundamental plasma physics understanding and model validation, to drive scenario development by integrating high performance core and boundary plasmas. Substantial increases in off-axis current drive efficiency from an innovative top launch system for EC power, and in pressure broadening for Alfven eigenmode control from a co-/counter-I p steerable off-axis neutral beam, all improve the prospects for optimization of future long pulse/steady state high performance tokamak operation. Fundamental studies into the modes that drive the evolution of the pedestal pressure profile and electron vs ion heat flux validate predictive models of pedestal recovery after ELMs. Understanding the physics mechanisms of ELM control and density pumpout by 3D magnetic perturbation fields leads to confident predictions for ITER and future devices. Validated modeling of high-Z shattered pellet injection for disruption mitigation, runaway electron dissipation, and techniques for disruption prediction and avoidance including machine learning, give confidence in handling disruptivity for future devices. For the non-nuclear phase of ITER, two actuators are identified to lower the L-H threshold power in hydrogen plasmas. With this physics understanding and suite of capabilities, a high poloidal beta optimized-core scenario with an internal transport barrier that projects nearly to Q = 10 in ITER at ∼8 MA was coupled to a detached divertor, and a near super H-mode optimized-pedestal scenario with co-I p beam injection was coupled to a radiative divertor. The hybrid core scenario was achieved directly, without the need for anomalous current diffusion, using off-axis current drive actuators. Also, a controller to assess proximity to stability limits and regulate β N in the ITER baseline scenario, based on plasma response to probing 3D fields, was demonstrated. Finally, innovative tokamak operation using a negative triangularity shape showed many attractive features for future pilot plant operation.
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| 7. |
- Mullins, Niamh, et al.
(author)
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Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors
- 2022
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In: Biological Psychiatry. - : Elsevier. - 0006-3223 .- 1873-2402. ; 91:3, s. 313-327
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Journal article (peer-reviewed)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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| 8. |
- Docherty, Anna R, et al.
(author)
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GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors.
- 2023
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In: The American journal of psychiatry. - : American Psychiatric Association Publishing. - 1535-7228 .- 0002-953X. ; 180:10, s. 723-738
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Journal article (peer-reviewed)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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| 12. |
- Shupe, M. D., et al.
(author)
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Overview of the MOSAiC expedition : Atmosphere
- 2022
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In: Elementa. - : University of California Press. - 2325-1026. ; 10:1
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Journal article (peer-reviewed)abstract
- With the Arctic rapidly changing, the needs to observe, understand, and model the changes are essential. To support these needs, an annual cycle of observations of atmospheric properties, processes, and interactions were made while drifting with the sea ice across the central Arctic during the Multidisciplinary drifting Observatory for the Study of Arctic Climate (MOSAiC) expedition from October 2019 to September 2020. An international team designed and implemented the comprehensive program to document and characterize all aspects of the Arctic atmospheric system in unprecedented detail, using a variety of approaches, and across multiple scales. These measurements were coordinated with other observational teams to explore crosscutting and coupled interactions with the Arctic Ocean, sea ice, and ecosystem through a variety of physical and biogeochemical processes. This overview outlines the breadth and complexity of the atmospheric research program, which was organized into 4 subgroups: atmospheric state, clouds and precipitation, gases and aerosols, and energy budgets. Atmospheric variability over the annual cycle revealed important influences from a persistent large-scale winter circulation pattern, leading to some storms with pressure and winds that were outside the interquartile range of past conditions suggested by long-term reanalysis. Similarly, the MOSAiC location was warmer and wetter in summer than the reanalysis climatology, in part due to its close proximity to the sea ice edge. The comprehensiveness of the observational program for characterizing and analyzing atmospheric phenomena is demonstrated via a winter case study examining air mass transitions and a summer case study examining vertical atmospheric evolution. Overall, the MOSAiC atmospheric program successfully met its objectives and was the most comprehensive atmospheric measurement program to date conducted over the Arctic sea ice. The obtained data will support a broad range of coupled-system scientific research and provide an important foundation for advancing multiscale modeling capabilities in the Arctic.
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| 13. |
- Carmona-Gutierrez, D., et al.
(author)
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Guidelines and recommendations on yeast cell death nomenclature
- 2018
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In: Microbial Cell. - : Shared Science Publishers OG. - 2311-2638. ; 5:1, s. 4-31
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Research review (peer-reviewed)abstract
- Elucidating the biology of yeast in its full complexity has major implications for science, medicine and industry. One of the most critical processes determining yeast life and physiology is cellular demise. However, the investigation of yeast cell death is a relatively young field, and a widely accepted set of concepts and terms is still missing. Here, we propose unified criteria for the definition of accidental, regulated, and programmed forms of cell death in yeast based on a series of morphological and biochemical criteria. Specifically, we provide consensus guidelines on the differential definition of terms including apoptosis, regulated necrosis, and autophagic cell death, as we refer to additional cell death routines that are relevant for the biology of (at least some species of) yeast. As this area of investigation advances rapidly, changes and extensions to this set of recommendations will be implemented in the years to come. Nonetheless, we strongly encourage the authors, reviewers and editors of scientific articles to adopt these collective standards in order to establish an accurate framework for yeast cell death research and, ultimately, to accelerate the progress of this vibrant field of research.
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| 15. |
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| 16. |
- Liu, DJ, et al.
(author)
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Schizophrenia risk conferred by rare protein-truncating variants is conserved across diverse human populations
- 2023
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In: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 55:3, s. 369-
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Journal article (peer-reviewed)abstract
- Schizophrenia (SCZ) is a chronic mental illness and among the most debilitating conditions encountered in medical practice. A recent landmark SCZ study of the protein-coding regions of the genome identified a causal role for ten genes and a concentration of rare variant signals in evolutionarily constrained genes1. This recent study—and most other large-scale human genetics studies—was mainly composed of individuals of European (EUR) ancestry, and the generalizability of the findings in non-EUR populations remains unclear. To address this gap, we designed a custom sequencing panel of 161 genes selected based on the current knowledge of SCZ genetics and sequenced a new cohort of 11,580 SCZ cases and 10,555 controls of diverse ancestries. Replicating earlier work, we found that cases carried a significantly higher burden of rare protein-truncating variants (PTVs) among evolutionarily constrained genes (odds ratio = 1.48; P = 5.4 × 10−6). In meta-analyses with existing datasets totaling up to 35,828 cases and 107,877 controls, this excess burden was largely consistent across five ancestral populations. Two genes (SRRM2 and AKAP11) were newly implicated as SCZ risk genes, and one gene (PCLO) was identified as shared by individuals with SCZ and those with autism. Overall, our results lend robust support to the rare allelic spectrum of the genetic architecture of SCZ being conserved across diverse human populations.
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| 17. |
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| 18. |
- Powers, M. B., et al.
(author)
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A Randomized Controlled Trial of Animated Versus Live Action Virtual Reality Therapy for Anxiety & Pain in a Level I Trauma Center
- 2018
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Conference paper (other academic/artistic)abstract
- While virtual reality exposure therapy (VRET) shows promise as a treatment for anxiety and pain (Powers & Emmelkamp, 2008), many users complain that computer-generated virtual reality (VR) stimuli appear unrealistic, eccentric, and too much like a video game (Kwon, Powell, & Chalmers, 2013). Historically, programmers using video game assets and computer-generated imagery (CGI) created VR content. While CGI can be used to make intricate virtual environments, unless there is a team of expert digital artists, the virtual stimulus may look unrealistic and exhibit a number of graphical glitches that could prove distracting in therapy. Furthermore, CGI often suffers from the uncanny valley effect, where CGI representations of people are perceived as unsettling as the representations become more lifelike. Thus, the only method to overcome the uncanny valley effect is to present the VR as less realistic (CGI) or photorealistic. In addition, current CGI VR packages are expensive and difficult to implement in widespread medical settings. Recently, however, an exciting alternative to traditional computer-generated VR has emerged: 360-Degree 3-D HD Video VR (Live Action). The benefit of Live Action VR as opposed to CGI VR is that it is photorealistic and doesn’t cause the uncanny valley effect of CGI. In addition, the projected cost of the end product is approximately $500 and delivered using a portable VR headset. In this RCT, participants in a Level I Trauma Center reporting pain (N = 78) were randomized to waitlist, 10-minutes of CGI VR, or 10-minutes of Live Action VR. Consistent with prediction, both VR conditions showed greater reduction in anxiety relative to waitlist (p < .05). However, there was no difference between the conditions. The two VR conditions also showed significantly greater reductions in pain (p < .001) and pain interference (p < .001) relative to the waitlist with no differences between conditions. As expected, participants rated Live Action VR significantly more realistic than CGI VR (p < .001) and reported a greater sense of being in the virtual world (p < .05). Finally, 92% of participants in the waitlist preferred to view the Live Action VR.
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| 19. |
- Hampton, Stephanie E., et al.
(author)
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Ecology under lake ice
- 2017
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In: Ecology Letters. - : Wiley. - 1461-023X .- 1461-0248. ; 20:1, s. 98-111
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Research review (peer-reviewed)abstract
- Winter conditions are rapidly changing in temperate ecosystems, particularly for those that experience periods of snow and ice cover. Relatively little is known of winter ecology in these systems, due to a historical research focus on summer ‘growing seasons’. We executed the first global quantitative synthesis on under-ice lake ecology, including 36 abiotic and biotic variables from 42 research groups and 101 lakes, examining seasonal differences and connections as well as how seasonal differences vary with geophysical factors. Plankton were more abundant under ice than expected; mean winter values were 43.2% of summer values for chlorophyll a, 15.8% of summer phytoplankton biovolume and 25.3% of summer zooplankton density. Dissolved nitrogen concentrations were typically higher during winter, and these differences were exaggerated in smaller lakes. Lake size also influenced winter-summer patterns for dissolved organic carbon (DOC), with higher winter DOC in smaller lakes. At coarse levels of taxonomic aggregation, phytoplankton and zooplankton community composition showed few systematic differences between seasons, although literature suggests that seasonal differences are frequently lake-specific, species-specific, or occur at the level of functional group. Within the subset of lakes that had longer time series, winter influenced the subsequent summer for some nutrient variables and zooplankton biomass.
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| 20. |
- Ankarcrona, M., et al.
(author)
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Current and future treatment of amyloid diseases
- 2016
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In: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 280:2, s. 177-202
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Research review (peer-reviewed)abstract
- There are more than 30 human proteins whose aggregation appears to cause degenerative maladies referred to as amyloid diseases or amyloidoses. These disorders are named after the characteristic cross--sheet amyloid fibrils that accumulate systemically or are localized to specific organs. In most cases, current treatment is limited to symptomatic approaches and thus disease-modifying therapies are needed. Alzheimer's disease is a neurodegenerative disorder with extracellular amyloid -peptide (A) fibrils and intracellular tau neurofibrillary tangles as pathological hallmarks. Numerous clinical trials have been conducted with passive and active immunotherapy, and small molecules to inhibit A formation and aggregation or to enhance A clearance; so far such clinical trials have been unsuccessful. Novel strategies are therefore required and here we will discuss the possibility of utilizing the chaperone BRICHOS to prevent A aggregation and toxicity. Type 2 diabetes mellitus is symptomatically treated with insulin. However, the underlying pathology is linked to the aggregation and progressive accumulation of islet amyloid polypeptide as fibrils and oligomers, which are cytotoxic. Several compounds have been shown to inhibit islet amyloid aggregation and cytotoxicity in vitro. Future animal studies and clinical trials have to be conducted to determine their efficacy in vivo. The transthyretin (TTR) amyloidoses are a group of systemic degenerative diseases compromising multiple organ systems, caused by TTR aggregation. Liver transplantation decreases the generation of misfolded TTR and improves the quality of life for a subgroup of this patient population. Compounds that stabilize the natively folded, nonamyloidogenic, tetrameric conformation of TTR have been developed and the drug tafamidis is available as a promising treatment. Read more articles from the symposium: Amyloid - a multifaceted player in human health and disease.
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| 21. |
- Geerts, Bart, et al.
(author)
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The COMBLE Campaign : A Study of Marine Boundary Layer Clouds in Arctic Cold-Air Outbreaks
- 2022
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In: Bulletin of The American Meteorological Society - (BAMS). - 0003-0007 .- 1520-0477. ; 103:5, s. E1371-E1389
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Journal article (peer-reviewed)abstract
- One of the most intense air mass transformations on Earth happens when cold air flows from frozen surfaces to much warmer open water in cold-air outbreaks (CAOs), a process captured beautifully in satellite imagery. Despite the ubiquity of the CAO cloud regime over high-latitude oceans, we have a rather poor understanding of its properties, its role in energy and water cycles, and its treatment in weather and climate models. The Cold-Air Outbreaks in the Marine Boundary Layer Experiment (COMBLE) was conducted to better understand this regime and its representation in models. COMBLE aimed to examine the relations between surface fluxes, boundary layer structure, aerosol, cloud, and precipitation properties, and mesoscale circulations in marine CAOs. Processes affecting these properties largely fall in a range of scales where boundary layer processes, convection, and precipitation are tightly coupled, which makes accurate representation of the CAO cloud regime in numerical weather prediction and global climate models most challenging. COMBLE deployed an Atmospheric Radiation Measurement Mobile Facility at a coastal site in northern Scandinavia (69°N), with additional instruments on Bear Island (75°N), from December 2019 to May 2020. CAO conditions were experienced 19% (21%) of the time at the main site (on Bear Island). A comprehensive suite of continuous in situ and remote sensing observations of atmospheric conditions, clouds, precipitation, and aerosol were collected. Because of the clouds’ well-defined origin, their shallow depth, and the broad range of observed temperature and aerosol concentrations, the COMBLE dataset provides a powerful modeling testbed for improving the representation of mixed-phase cloud processes in large-eddy simulations and large-scale models.
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| 22. |
- Pustovalova, Y., et al.
(author)
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NUScon: a community-driven platform for quantitative evaluation of nonuniform sampling in NMR
- 2021
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In: Magnetic Resonance. - : Copernicus GmbH. - 2699-0016. ; 2:2, s. 843-861
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Journal article (peer-reviewed)abstract
- Although the concepts of nonuniform sampling (NUS) and non-Fourier spectral reconstruction in multidimensional NMR began to emerge 4 decades ago (Bodenhausen and Ernst, 1981; Barna and Laue, 1987), it is only relatively recently that NUS has become more commonplace. Advantages of NUS include the ability to tailor experiments to reduce data collection time and to improve spectral quality, whether through detection of closely spaced peaks (i.e., “resolution”) or peaks of weak intensity (i.e., “sensitivity”). Wider adoption of these methods is the result of improvements in computational performance, a growing abundance and flexibility of software, support from NMR spectrometer vendors, and the increased data sampling demands imposed by higher magnetic fields. However, the identification of best practices still remains a significant and unmet challenge. Unlike the discrete Fourier transform, non-Fourier methods used to reconstruct spectra from NUS data are nonlinear, depend on the complexity and nature of the signals, and lack quantitative or formal theory describing their performance. Seemingly subtle algorithmic differences may lead to significant variabilities in spectral qualities and artifacts. A community-based critical assessment of NUS challenge problems has been initiated, called the “Nonuniform Sampling Contest” (NUScon), with the objective of determining best practices for processing and analyzing NUS experiments. We address this objective by constructing challenges from NMR experiments that we inject with synthetic signals, and we process these challenges using workflows submitted by the community. In the initial rounds of NUScon our aim is to establish objective criteria for evaluating the quality of spectral reconstructions. We present here a software package for performing the quantitative analyses, and we present the results from the first two rounds of NUScon. We discuss the challenges that remain and present a roadmap for continued community-driven development with the ultimate aim of providing best practices in this rapidly evolving field. The NUScon software package and all data from evaluating the challenge problems are hosted on the NMRbox platform.
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| 25. |
- Berlin Kolm, Sofia, et al.
(author)
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Genetic diversity, population structure and phenotypic variation in European Salix viminalis L. (Salicaceae)
- 2014
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In: Tree Genetics & Genomes. - : Springer Science and Business Media LLC. - 1614-2942 .- 1614-2950. ; 10:6, s. 1595-1610
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Journal article (peer-reviewed)abstract
- To investigate the potential of association genetics for willow breeding, Salix viminalis germplasm was assembled from UK and Swedish collections (comprising accessions from several European countries) and new samples collected from nature. A subset of the germplasm was planted at two sites (UK and Sweden), genotyped using 38 SSR markers and assessed for phenological and biomass traits. Population structure, genetic differentiation (F-ST) and quantitative trait differentiation (Q(ST)) were investigated. The extent and patterns of trait adaptation were assessed by comparing F-ST and Q(ST) parameters. Of the 505 genotyped diploid accessions, 27 % were not unique. Genetic diversity was high: 471 alleles was amplified; the mean number of alleles per locus was 13.46, mean observed heterozygosity was 0.55 and mean expected heterozygosity was 0.62. Bayesian clustering identified four subpopulations which generally corresponded to Western Russia, Western Europe, Eastern Europe and Sweden. All pairwise F-ST values were highly significant (p<0.001) with the greatest genetic differentiation detected between the Western Russian and the Western European subpopulations (F-ST = 0.12), and the smallest between the Swedish and Eastern European populations (F-ST = 0.04). The Swedish population also had the highest number of identical accessions, supporting the view that S. viminalis was introduced into this country and has been heavily influenced by humans. Q(ST) values were high for growth cessation and leaf senescence, and to some extent stem diameter, but low for bud burst time and shoot number. Overall negative clines between longitudinal coordinates and leaf senescence, bud burst and stem diameter were also found.
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| 26. |
- Gei, Maga, et al.
(author)
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Legume abundance along successional and rainfall gradients in Neotropical forests
- 2018
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In: Nature Ecology & Evolution. - : Springer Science and Business Media LLC. - 2397-334X. ; 2:7
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Journal article (peer-reviewed)abstract
- The nutrient demands of regrowing tropical forests are partly satisfied by nitrogen-fixing legume trees, but our understanding of the abundance of those species is biased towards wet tropical regions. Here we show how the abundance of Leguminosae is affected by both recovery from disturbance and large-scale rainfall gradients through a synthesis of forest inventory plots from a network of 42 Neotropical forest chronosequences. During the first three decades of natural forest regeneration, legume basal area is twice as high in dry compared with wet secondary forests. The tremendous ecological success of legumes in recently disturbed, water-limited forests is likely to be related to both their reduced leaflet size and ability to fix N2, which together enhance legume drought tolerance and water-use efficiency. Earth system models should incorporate these large-scale successional and climatic patterns of legume dominance to provide more accurate estimates of the maximum potential for natural nitrogen fixation across tropical forests.
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| 27. |
- Halban, Philippe A, et al.
(author)
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β-Cell Failure in Type 2 Diabetes: Postulated Mechanisms and Prospects for Prevention and Treatment.
- 2014
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In: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 37:6, s. 1751-1758
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Journal article (peer-reviewed)abstract
- This article examines the foundation of β-cell failure in type 2 diabetes (T2D) and suggests areas for future research on the underlying mechanisms that may lead to improved prevention and treatment.RESEARCH DESIGN AND METHODS: A group of experts participated in a conference on 14-16 October 2013 cosponsored by the Endocrine Society and the American Diabetes Association. A writing group prepared this summary and recommendations.RESULTS: The writing group based this article on conference presentations, discussion, and debate. Topics covered include genetic predisposition, foundations of β-cell failure, natural history of β-cell failure, and impact of therapeutic interventions.CONCLUSIONS: β-Cell failure is central to the development and progression of T2D. It antedates and predicts diabetes onset and progression, is in part genetically determined, and often can be identified with accuracy even though current tests are cumbersome and not well standardized. Multiple pathways underlie decreased β-cell function and mass, some of which may be shared and may also be a consequence of processes that initially caused dysfunction. Goals for future research include to 1) impact the natural history of β-cell failure; 2) identify and characterize genetic loci for T2D; 3) target β-cell signaling, metabolic, and genetic pathways to improve function/mass; 4) develop alternative sources of β-cells for cell-based therapy; 5) focus on metabolic environment to provide indirect benefit to β-cells; 6) improve understanding of the physiology of responses to bypass surgery; and 7) identify circulating factors and neuronal circuits underlying the axis of communication between the brain and β-cells.
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| 28. |
- Halban, Philippe A, et al.
(author)
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β-cell Failure in Type 2 Diabetes: Postulated Mechanisms and Prospects for Prevention and Treatment.
- 2014
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In: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 1945-7197 .- 0021-972X. ; 99:6, s. 1983-1992
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Journal article (peer-reviewed)abstract
- Objective: This report examines the foundation of β-cell failure in type 2 diabetes and suggests areas for future research on the underlying mechanisms that may lead to improved prevention and treatment. Participants: A group of experts participated in a conference on October 14-16, 2013 cosponsored by The Endocrine Society and the American Diabetes Association. A writing group prepared this summary and recommendations. Evidence: The writing group based this report on conference presentations, discussion, and debate. Topics covered include genetic predisposition, the foundations of β-cell failure, natural history of β-cell failure, and impact of therapeutic interventions. Conclusions: β-cell failure is central to the development and progression of type 2 diabetes. It antedates and predicts diabetes onset and progression, is in part genetically determined, and often can be identified with accuracy even though current tests are cumbersome and not well standardized. Multiple pathways underlie decreased β-cell function and mass, some of which may be shared and may also be a consequence of processes that initially caused dysfunction. Goals for future research include: 1) Impact the natural history of β-cell failure; 2) Identify and characterize genetic loci for type 2 diabetes; 3) Target β-cell signaling, metabolic, and genetic pathways to improve function/mass; 4) Develop alternative sources of β-cells for cell-based therapy; 5) Focus on metabolic environment to provide indirect benefit to β-cells; 6) Improve understanding of the physiology of responses to bypass surgery; 7) Identify circulating factors and neuronal circuits underlying the axis of communication between the brain and β-cells.
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| 29. |
- Hallingbäck, Henrik, et al.
(author)
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Association mapping in Salix viminalis L. (Salicaceae) - identification of candidate genes associated with growth and phenology
- 2016
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In: Global Change Biology Bioenergy. - : Wiley. - 1757-1693 .- 1757-1707. ; 8:3, s. 670-685
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Journal article (peer-reviewed)abstract
- Willow species (Salix) are important as short-rotation biomass crops for bioenergy, which creates a demand for faster genetic improvement and breeding through deployment of molecular marker-assisted selection (MAS). To find markers associated with important adaptive traits, such as growth and phenology, for use in MAS, we genetically dissected the trait variation of a Salix viminalis (L.) population of 323 accessions. The accessions were sampled throughout northern Europe and were established at two field sites in Pustnas, Sweden, and at Woburn, UK, offering the opportunity to assess the impact of genotype-by-environment interactions (GxE) on trait-marker associations. Field measurements were recorded for growth and phenology traits. The accessions were genotyped using 1536 SNP markers developed from phenology candidate genes and from genes previously observed to be differentially expressed in contrasting environments. Association mapping between 1233 of these SNPs and the measured traits was performed taking into account population structure and threshold selection bias. At a false discovery rate (FDR) of 0.2, 29 SNPs were associated with bud burst, leaf senescence, number of shoots or shoot diameter. The percentage of accession variation explained by these associations ranged from 0.3% to 4.4%, suggesting that the studied traits are controlled by many loci of limited individual impact. Despite this, a SNP in the EARLY FLOWERING 3 gene was repeatedly associated (FDR<0.2) with bud burst. The rare homozygous genotype exhibited 0.4-1.0 lower bud burst scores than the other genotype classes on a five-grade scale. Consequently, this marker could be promising for use in MAS and the gene deserves further study. Otherwise, associations were less consistent across sites, likely due to their small estimates and to considerable GxE interactions indicated by multivariate association analyses and modest trait accession correlations across sites (0.32-0.61).
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| 30. |
- Lifke, V., et al.
(author)
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Elecsys® Total-Tau and Phospho-Tau (181P) CSF assays: Analytical performance of the novel, fully automated immunoassays for quantification of tau proteins in human cerebrospinal fluid
- 2019
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In: Clinical Biochemistry. - : Elsevier BV. - 0009-9120. ; 72, s. 30-38
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Journal article (peer-reviewed)abstract
- Background: Total tau (tTau) and phosphorylated 181P tau (pTau) are supportive diagnostic cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease. Manual CSF tau assays are limited by lot-to-lot and between-laboratory variability and long incubation/turnaround times. Elecsys® Total-Tau CSF and Phospho-Tau (181P) CSF immunoassays were developed for fully automated cobas e analyzers, allowing broader access in clinical practice and trials. Methods: Analytical performance, reproducibility, method comparisons with commercially available assays, and lot-to-lot and platform comparability (cobas e 601/411) of the Elecsys® CSF assays were assessed. Tau distributions and concentration ranges were evaluated in CSF samples from two clinical cohorts. Results: Both assays showed high sensitivity (limit of quantitation [LoQ]: 63 pg/mL [tTau]; 4 pg/mL [pTau]) and linearity over the measuring range (80–1300 pg/mL; 8–120 pg/mL), which covered the entire concentration range measured in clinical samples. Lot-to-lot and platform comparability demonstrated good consistency (Pearson's r: 0.998; 1.000). Multicenter evaluation coefficients of variation (CVs): repeatability, < 1.8%; intermediate precision, < 2.8%; between-laboratory variability, < 2.7% (both assays); and total reproducibility, < 6.7% (tTau) and < 4.7% (pTau). Elecsys® CSF assays demonstrated good correlation with commercially available tau assays. Conclusions: Elecsys® Total-Tau CSF and Phospho-Tau (181P) CSF assays demonstrate good analytical performance with clinically relevant measuring ranges; data support their use in clinical trials and practice. © 2019
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| 32. |
- Storm, Petter, et al.
(author)
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Conserved features of cancer cells define their sensitivity to HAMLET-induced death; c-Myc and glycolysis.
- 2011
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In: Oncogene. - : Springer Science and Business Media LLC. - 1476-5594 .- 0950-9232. ; 30, s. 4765-4779
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Journal article (peer-reviewed)abstract
- HAMLET is the first member of a new family of tumoricidal protein-lipid complexes that kill cancer cells broadly, while sparing healthy, differentiated cells. Many and diverse tumor cell types are sensitive to the lethal effect, suggesting that HAMLET identifies and activates conserved death pathways in cancer cells. Here, we investigated the molecular basis for the difference in sensitivity between cancer cells and healthy cells. Using a combination of small-hairpin RNA (shRNA) inhibition, proteomic and metabolomic technology, we identified the c-Myc oncogene as one essential determinant of HAMLET sensitivity. Increased c-Myc expression levels promoted sensitivity to HAMLET and shRNA knockdown of c-Myc suppressed the lethal response, suggesting that oncogenic transformation with c-Myc creates a HAMLET-sensitive phenotype. Furthermore, HAMLET sensitivity was modified by the glycolytic state of tumor cells. Glucose deprivation sensitized tumor cells to HAMLET-induced cell death and in the shRNA screen, hexokinase 1 (HK1), 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 1 and hypoxia-inducible factor 1α modified HAMLET sensitivity. HK1 was shown to bind HAMLET in a protein array containing ∼8000 targets, and HK activity decreased within 15 min of HAMLET treatment, before morphological signs of tumor cell death. In parallel, HAMLET triggered rapid metabolic paralysis in carcinoma cells. Tumor cells were also shown to contain large amounts of oleic acid and its derivatives already after 15 min. The results identify HAMLET as a novel anti-cancer agent that kills tumor cells by exploiting unifying features of cancer cells such as oncogene addiction or the Warburg effect.
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| 33. |
- Wang, Gang, et al.
(author)
-
Photovoltaic Blend Microstructure for High Efficiency Post-Fullerene Solar Cells. To Tilt or Not To Tilt?
- 2019
-
In: Journal of the American Chemical Society. - : American Chemical Society (ACS). - 0002-7863 .- 1520-5126. ; 141:34, s. 13410-13420
-
Journal article (peer-reviewed)abstract
- Achieving efficient polymer solar cells (PSCs) requires a structurally optimal donor-acceptor heterojunction morphology. Here we report the combined experimental and theoretical characterization of a benzodithiophene-benzo-thiadiazole donor polymer series (PBTZF4-R; R = alkyl substituent) blended with the non-fullerene acceptor ITIC-Th and analyze the effects of substituent dimensions on blend morphology, charge transport, carrier dynamics, and PSC metrics. Varying substituent dimensions has a pronounced effect on the blend morphology with a direct link between domain purity, to some extent domain dimensions, and charge generation and collection. The polymer with the smallest alkyl substituent yields the highest PSC power conversion efficiency (PCE, 11%), reflecting relatively small, high-purity domains and possibly benefiting from "matched" donor polymer-small molecule acceptor orientations. The distinctive morphologies arising from the substituents are investigated using molecular dynamics (MD) simulations which reveal that substituent dimensions dictate a well-defined set of polymer conformations, in turn driving chain aggregation and, ultimately, the various film morphologies and mixing with acceptor small molecules. A straightforward energetic parameter explains the experimental polymer domain morphological trends, hence PCE, and suggests strategies for substituent selection to optimize PSC materials morphologies.
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| 34. |
- Cai, Qing, et al.
(author)
-
Enhanced expression of VEGF-A in β cells increases endothelial cell number but impairs islet morphogenesis and β cell proliferation.
- 2012
-
In: Developmental Biology. - : Elsevier BV. - 0012-1606 .- 1095-564X. ; 367:1, s. 40-54
-
Journal article (peer-reviewed)abstract
- There is a reciprocal interaction between pancreatic islet cells and vascular endothelial cells (EC) in which EC-derived signals promote islet cell differentiation and islet development while islet cell-derived angiogenic factors promote EC recruitment and extensive islet vascularization. To examine the role of angiogenic factors in the coordinated development of islets and their associated vessels, we used a "tet-on" inducible system (mice expressing rat insulin promoter-reverse tetracycline activator transgene and a tet-operon-angiogenic factor transgene) to increase the β cell production of vascular endothelial growth factor-A (VEGF-A), angiopoietin-1 (Ang1), or angiopoietin-2 (Ang2) during islet cell differentiation and islet development. In VEGF-A overexpressing embryos, ECs began to accumulate around epithelial tubes residing in the central region of the developing pancreas (associated with endocrine cells) as early as embryonic day 12.5 (E12.5) and increased dramatically by E16.5. While α and β cells formed islet cell clusters in control embryos at E16.5, the increased EC population perturbed endocrine cell differentiation and islet cell clustering in VEGF-A overexpressing embryos. With continued overexpression of VEGF-A, α and β cells became scattered, remained adjacent to ductal structures, and never coalesced into islets, resulting in a reduction in β cell proliferation and β cell mass at postnatal day 1. A similar impact on islet morphology was observed when VEGF-A was overexpressed in β cells during the postnatal period. In contrast, increased expression of Ang1 or Ang2 in β cells in developing or adult islets did not alter islet differentiation, development, or morphology, but altered islet EC ultrastructure. These data indicate that (1) increased EC number does not promote, but actually impairs β cell proliferation and islet formation; (2) the level of VEGF-A production by islet endocrine cells is critical for islet vascularization during development and postnatally; (3) angiopoietin-Tie2 signaling in endothelial cells does not have a crucial role in the development or maintenance of islet vascularization.
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| 35. |
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| 36. |
- Carl, Emily, et al.
(author)
-
Virtual reality exposure therapy for anxiety and related disorders : A meta-analysis of randomized controlled trials
- 2019
-
In: Journal of Anxiety Disorders. - : Elsevier BV. - 0887-6185 .- 1873-7897. ; 61, s. 27-36
-
Journal article (peer-reviewed)abstract
- Trials of virtual reality exposure therapy (VRET) for anxiety-related disorders have proliferated in number and diversity since our previous meta-analysis that examined 13 total trials, most of which were for specific phobias (Powers & Emmelkamp, 2008). Since then, new trials have compared VRET to more diverse anxiety and related disorders including social anxiety disorder (SAD), posttraumatic stress disorder (PTSD), and panic disorder (PD) with and without agoraphobia. With the availability of this data, it is imperative to re-examine the efficacy of VRET for anxiety. A literature search for randomized controlled trials of VRET versus control or in vivo exposure yielded 30 studies with 1057 participants. Fourteen studies tested VRET for specific phobias, 8 for SAD or performance anxiety, 5 for PTSD, and 3 for PD. A random effects analysis estimated a large effect size for VRET versus waitlist (g = 0.90) and a medium to large effect size for VRET versus psychological placebo conditions (g = 0.78). A comparison of VRET and in vivo conditions did not show significantly different effect sizes (g = −0.07). These findings were relatively consistent across disorders. A meta-regression analysis revealed that larger sample sizes were associated with lower effect sizes in VRET versus control comparisons (β = −0.007, p < 0.05). These results indicate that VRET is an effective and equal medium for exposure therapy.
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| 37. |
- Chazdon, Robin L., et al.
(author)
-
Carbon sequestration potential of second-growth forest regeneration in the Latin American tropics
- 2016
-
In: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 2:5
-
Journal article (peer-reviewed)abstract
- Regrowth of tropical secondary forests following complete or nearly complete removal of forest vegetation actively stores carbon in aboveground biomass, partially counterbalancing carbon emissions from deforestation, forest degradation, burning of fossil fuels, and other anthropogenic sources. We estimate the age and spatial extent of lowland second-growth forests in the Latin American tropics and model their potential aboveground carbon accumulation over four decades. Our model shows that, in 2008, second-growth forests (1 to 60 years old) covered 2.4 million km2 of land (28.1% of the total study area). Over 40 years, these lands can potentially accumulate a total aboveground carbon stock of 8.48 Pg C (petagrams of carbon) in aboveground biomass via low-cost natural regeneration or assisted regeneration, corresponding to a total CO2 sequestration of 31.09 Pg CO2. This total is equivalent to carbon emissions from fossil fuel use and industrial processes in all of Latin America and the Caribbean from 1993 to 2014. Ten countries account for 95% of this carbon storage potential, led by Brazil, Colombia, Mexico, and Venezuela. We model future land-use scenarios to guide national carbon mitigation policies. Permitting natural regeneration on 40% of lowland pastures potentially stores an additional 2.0 Pg C over 40 years. Our study provides information and maps to guide national-level forest-based carbon mitigation plans on the basis of estimated rates of natural regeneration and pasture abandonment. Coupled with avoided deforestation and sustainable forest management, natural regeneration of second-growth forests provides a low-cost mechanism that yields a high carbon sequestration potential with multiple benefits for biodiversity and ecosystem services.
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| 38. |
- Cusack, Daniela Francis, et al.
(author)
-
Tradeoffs and Synergies in Tropical Forest Root Traits and Dynamics for Nutrient and Water Acquisition : Field and Modeling Advances
- 2021
-
In: Frontiers in Forests and Global Change. - : Frontiers Media S.A.. - 2624-893X. ; 4
-
Research review (peer-reviewed)abstract
- Vegetation processes are fundamentally limited by nutrient and water availability, the uptake of which is mediated by plant roots in terrestrial ecosystems. While tropical forests play a central role in global water, carbon, and nutrient cycling, we know very little about tradeoffs and synergies in root traits that respond to resource scarcity. Tropical trees face a unique set of resource limitations, with rock-derived nutrients and moisture seasonality governing many ecosystem functions, and nutrient versus water availability often separated spatially and temporally. Root traits that characterize biomass, depth distributions, production and phenology, morphology, physiology, chemistry, and symbiotic relationships can be predictive of plants’ capacities to access and acquire nutrients and water, with links to aboveground processes like transpiration, wood productivity, and leaf phenology. In this review, we identify an emerging trend in the literature that tropical fine root biomass and production in surface soils are greatest in infertile or sufficiently moist soils. We also identify interesting paradoxes in tropical forest root responses to changing resources that merit further exploration. For example, specific root length, which typically increases under resource scarcity to expand the volume of soil explored, instead can increase with greater base cation availability, both across natural tropical forest gradients and in fertilization experiments. Also, nutrient additions, rather than reducing mycorrhizal colonization of fine roots as might be expected, increased colonization rates under scenarios of water scarcity in some forests. Efforts to include fine root traits and functions in vegetation models have grown more sophisticated over time, yet there is a disconnect between the emphasis in models characterizing nutrient and water uptake rates and carbon costs versus the emphasis in field experiments on measuring root biomass, production, and morphology in response to changes in resource availability. Closer integration of field and modeling efforts could connect mechanistic investigation of fine-root dynamics to ecosystem-scale understanding of nutrient and water cycling, allowing us to better predict tropical forest-climate feedbacks.
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| 39. |
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| 40. |
- Dorigo, Wouter, et al.
(author)
-
The International Soil Moisture Network : Serving Earth system science for over a decade
- 2021
-
In: Hydrology and Earth System Sciences. - : Copernicus GmbH. - 1027-5606 .- 1607-7938. ; 25:11, s. 5749-5804
-
Research review (peer-reviewed)abstract
- In 2009, the International Soil Moisture Network (ISMN) was initiated as a community effort, funded by the European Space Agency, to serve as a centralised data hosting facility for globally available in situ soil moisture measurements . The ISMN brings together in situ soil moisture measurements collected and freely shared by a multitude of organisations, harmonises them in terms of units and sampling rates, applies advanced quality control, and stores them in a database. Users can freely retrieve the data from this database through an online web portal (https://ismn.earth/en/, last access: 28 October 2021). Meanwhile, the ISMN has evolved into the primary in situ soil moisture reference database worldwide, as evidenced by more than 3000 active users and over 1000 scientific publications referencing the data sets provided by the network. As of July 2021, the ISMN now contains the data of 71 networks and 2842 stations located all over the globe, with a time period spanning from 1952 to the present. The number of networks and stations covered by the ISMN is still growing, and approximately 70 % of the data sets contained in the database continue to be updated on a regular or irregular basis. The main scope of this paper is to inform readers about the evolution of the ISMN over the past decade, including a description of network and data set updates and quality control procedures. A comprehensive review of the existing literature making use of ISMN data is also provided in order to identify current limitations in functionality and data usage and to shape priorities for the next decade of operations of this unique community-based data repository.
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| 41. |
- Gomaa, Fatma, et al.
(author)
-
Multiple integrated metabolic strategies allow foraminiferan protists to thrive in anoxic marine sediments
- 2021
-
In: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 7:22
-
Journal article (peer-reviewed)abstract
- Oceanic deoxygenation is increasingly affecting marine ecosystems; many taxa will be severely challenged, yet certain nominally aerobic foraminifera (rhizarian protists) thrive in oxygen-depleted to anoxic, sometimes sulfidic, sediments uninhabitable to most eukaryotes. Gene expression analyses of foraminifera common to severely hypoxic or anoxic sediments identified metabolic strategies used by this abundant taxon. In field-collected and laboratory-incubated samples, foraminifera expressed denitrification genes regardless of oxygen regime with a putative nitric oxide dismutase, a characteristic enzyme of oxygenic denitrification. A pyruvate:ferredoxin oxidoreductase was highly expressed, indicating the capability for anaerobic energy generation during exposure to hypoxia and anoxia. Near-complete expression of a diatom’s plastid genome in one foraminiferal species suggests kleptoplasty or sequestration of functional plastids, conferring a metabolic advantage despite the host living far below the euphotic zone. Through a unique integration of functions largely unrecognized among “typical” eukaryotes, benthic foraminifera represent winning microeukaryotes in the face of ongoing oceanic deoxygenation.
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| 42. |
- Hammarström, Per, et al.
(author)
-
Sequence-dependent denaturation energetics : A major determinant in amyloid disease diversity
- 2002
-
In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 99:SUPPL. 4, s. 16427-16432
-
Conference paper (other academic/artistic)abstract
- Several misfolding diseases commence when a secreted folded protein encounters a partially denaturing microenvironment, enabling its self assembly into amyloid. Although amyloidosis is modulated by numerous environmental and genetic factors, single point mutations within the amyloidogenic protein can dramatically influence disease phenotype. Mutations that destabilize the native state predispose an individual to disease, however, thermodynamic stability alone does not reliably predict disease severity. Here we show that the rate of transthyretin (TTR) tetramer dissociation required for amyloid formation is strongly influenced by mutation (V30M, L55P, T119M, V122I), with rapid rates exacerbating and slow rates reducing amyloidogenicity. Although these rates are difficult to predict a priori, they notably influence disease penetrance and age of onset. L55P TTR exhibits severe pathology because the tetramer both dissociates quickly and is highly destabilized. Even though V30M and L55P TTR are similarly destabilized, the V30M disease phenotype is milder because V30M dissociates more slowly, even slower than wild type (WT). Although WT and V122I TTR have nearly equivalent tetramer stabilities, V122I cardiomyopathy, unlike WT cardiomyopathy, has nearly complete penetrance-presumably because of its 2-fold increase in dissociation rate. We show that the T119M homotetramer exhibits kinetic stabilization and therefore dissociates exceedingly slowly, likely explaining how it functions to protect V30M/T119M compound heterozygotes from disease. An understanding of how mutations influence both the kinetics and thermodynamics of misfolding allows us to rationalize the phenotypic diversity of amyloid diseases, especially when considered in concert with other genetic and environmental data.
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| 43. |
- Hannan, Johanna L., et al.
(author)
-
Impaired contraction and decreased detrusor innervation in a female rat model of pelvic neuropraxia
- 2017
-
In: International Urogynecology Journal. - : Springer Science and Business Media LLC. - 0937-3462 .- 1433-3023. ; 28:7, s. 1049-1056
-
Journal article (peer-reviewed)abstract
- Introduction and hypothesis: Bilateral pelvic nerve injury (BPNI) is a model of post-radical hysterectomy neuropraxia, a common sequela. This study assessed the time course of changes to detrusor autonomic innervation, smooth muscle (SM) content and cholinergic-mediated contraction post-BPNI. Methods: Female Sprague–Dawley rats underwent BPNI or sham surgery and were evaluated 3, 7, 14, and 30 days post-BPNI (n = 8/group). Electrical field-stimulated (EFS) and carbachol-induced contractions were measured. Gene expression was assessed by qPCR for muscarinic receptor types 2 (M2) and 3 (M3), collagen type 1α1 and 3α1, and SM actin. Western blots measured M2 and M3 protein expression. Bladder sections were stained with Masson’s trichrome for SM content and immunofluorescence staining for nerve terminals expressing vesicular acetylcholine transporter (VAChT), tyrosine hydroxylase (TH), and neuronal nitric oxide synthase (nNOS). Results: Bilateral pelvic nerve injury caused larger bladders with less SM content and increased collagen type 1α1 and 3α1 gene expression. At early time points, cholinergic-mediated contraction increased, whereas EFS-mediated contraction decreased and returned to baseline by 30 days. Protein and gene expression of M3 was decreased 3 and 7 days post-BPNI, whereas M2 was unchanged. TH nerve terminals surrounding the detrusor decreased in all BPNI groups, whereas VAChT and nNOS terminals decreased 14 and 30 days post-BPNI. Conclusions: Bilateral pelvic nerve injury increased bladder size, impaired contractility, and decreased SM and autonomic innervation. Therapeutic strategies preventing nerve injury-mediated decline in neuronal input and SM content may prevent the development of a neurogenic bladder and improve quality of life after invasive pelvic surgery.
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| 44. |
- Hartmann, Henrik, et al.
(author)
-
Climate Change Risks to Global Forest Health : Emergence of Unexpected Events of Elevated Tree Mortality Worldwide
- 2022
-
In: Annual Review of Plant Biology. - : Annual Reviews. - 1543-5008 .- 1545-2123. ; 73, s. 673-702
-
Research review (peer-reviewed)abstract
- Recent observations of elevated tree mortality following climate extremes, like heat and drought, raise concerns about climate change risks to global forest health. We currently lack both sufficient data and understanding to identify whether these observations represent a global trend toward increasing tree mortality. Here, we document events of sudden and unexpected elevated tree mortality following heat and drought events in ecosystems that previously were considered tolerant or not at risk of exposure. These events underscore the fact that climate change may affect forests with unexpected force in the future. We use the events as examples to highlight current difficulties and challenges for realistically predicting such tree mortality events and the uncertainties about future forest condition. Advances in remote sensing technology and greater availably of high-resolution data, from both field assessments and satellites, are needed to improve both understanding and prediction of forest responses to future climate change.
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| 45. |
- Hernandez, Frank J, et al.
(author)
-
Noninvasive imaging of Staphylococcus aureus infections with a nuclease-activated probe
- 2014
-
In: Nature Medicine. - : Nature Publishing Group. - 1078-8956 .- 1546-170X. ; 20:3, s. 301-306
-
Journal article (peer-reviewed)abstract
- Technologies that enable the rapid detection and localization of bacterial infections in living animals could address an unmet need for infectious disease diagnostics. We describe a molecular imaging approach for the specific, noninvasive detection of S. aureus based on the activity of the S. aureus secreted nuclease, micrococcal nuclease (MN). Several short synthetic oligonucleotides, rendered resistant to mammalian serum nucleases by various chemical modifications and flanked with a fluorophore and quencher, were activated upon degradation by purified MN and in S. aureus culture supernatants. A probe consisting of a pair of deoxythymidines flanked by several 2′-O-methyl-modified nucleotides was activated in culture supernatants of S. aureus but not in culture supernatants of several other pathogenic bacteria. Systemic administration of this probe to mice bearing S. aureus muscle infections resulted in probe activation at the infection sites in an MN-dependent manner. This new bacterial imaging approach has potential clinical applicability for infections with S. aureus and several other medically important pathogens. © 2014 Nature America, Inc.
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| 46. |
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| 47. |
- Letcher, Susan G., et al.
(author)
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Environmental gradients and the evolution of successional habitat specialization : a test case with 14 Neotropical forest sites
- 2015
-
In: Journal of Ecology. - : Wiley. - 0022-0477 .- 1365-2745. ; 103:5
-
Journal article (peer-reviewed)abstract
- * Successional gradients are ubiquitous in nature, yet few studies have systematically examined the evolutionary origins of taxa that specialize at different successional stages. Here we quantify successional habitat specialization in Neotropical forest trees and evaluate its evolutionary lability along a precipitation gradient. Theoretically, successional habitat specialization should be more evolutionarily conserved in wet forests than in dry forests due to more extreme microenvironmental differentiation between early and late-successional stages in wet forest. * We applied a robust multinomial classification model to samples of primary and secondary forest trees from 14 Neotropical lowland forest sites spanning a precipitation gradient from 788 to 4000 mm annual rainfall, identifying species that are old-growth specialists and secondary forest specialists in each site. We constructed phylogenies for the classified taxa at each site and for the entire set of classified taxa and tested whether successional habitat specialization is phylogenetically conserved. We further investigated differences in the functional traits of species specializing in secondary vs. old-growth forest along the precipitation gradient, expecting different trait associations with secondary forest specialists in wet vs. dry forests since water availability is more limiting in dry forests and light availability more limiting in wet forests. * Successional habitat specialization is non-randomly distributed in the angiosperm phylogeny, with a tendency towards phylogenetic conservatism overall and a trend towards stronger conservatism in wet forests than in dry forests. However, the specialists come from all the major branches of the angiosperm phylogeny, and very few functional traits showed any consistent relationships with successional habitat specialization in either wet or dry forests. * Synthesis. The niche conservatism evident in the habitat specialization of Neotropical trees suggests a role for radiation into different successional habitats in the evolution of species-rich genera, though the diversity of functional traits that lead to success in different successional habitats complicates analyses at the community scale. Examining the distribution of particular lineages with respect to successional gradients may provide more insight into the role of successional habitat specialization in the evolution of species-rich taxa.
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| 48. |
- Metson, Genevieve, 1988-, et al.
(author)
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Socio-environmental consideration of phosphorus flows in the urban sanitation chain of contrasting cities
- 2018
-
In: Regional Environmental Change. - Heildelberg : Springer. - 1436-3798 .- 1436-378X. ; 18:5, s. 1387-1401
-
Journal article (peer-reviewed)abstract
- Understanding how cities can transform organic waste into a valuable resource is critical to urban sustainability. The capture and recycling of phosphorus (P), and other essential nutrients, from human excreta is particularly important as an alternative organic fertilizer source for agriculture. However, the complex set of socio-environmental factors influencing urban human excreta management is not yet sufficiently integrated into sustainable P research. Here, we synthesize information about the pathways P can take through urban sanitation systems along with barriers and facilitators to P recycling across cities. We examine five case study cities by using a sanitation chains approach: Accra, Ghana; Buenos Aires, Argentina; Beijing, China; Baltimore, USA; and London, England. Our cross-city comparison shows that London and Baltimore recycle a larger percentage of P from human excreta back to agricultural lands than other cities, and that there is a large diversity in socio-environmental factors that affect the patterns of recycling observed across cities. Our research highlights conditions that may be "necessary but not sufficient" for P recycling, including access to capital resources. Path dependencies of large sanitation infrastructure investments in the Global North contrast with rapidly urbanizing cities in the Global South, which present opportunities for alternative sanitation development pathways. Understanding such city-specific social and environmental barriers to P recycling options could help address multiple interacting societal objectives related to sanitation and provide options for satisfying global agricultural nutrient demand.
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| 49. |
- Minns, Sean, et al.
(author)
-
Immersive 3D exposure-based treatment for spider fear : A randomized controlled trial
- 2018
-
In: Journal of Anxiety Disorders. - : Elsevier. - 0887-6185 .- 1873-7897. ; 58, s. 1-7
-
Journal article (peer-reviewed)abstract
- Stereoscopic 3D gives the viewer the same shape, size, perspective and depth they would experience viewing the real world and could mimic the perceptual threat cues present in real life. This is the first study to investigate whether an immersive stereoscopic 3D video exposure-based treatment would be effective in reducing fear of spiders. Participants with a fear of spiders (N = 77) watched two psychoeducational videos with facts about spiders and phobias. They were then randomized to a treatment condition that watched a single session of a stereoscopic 3D immersive video exposure-based treatment (six 5-min exposures) delivered through a virtual reality headset or a psychoeducation only control condition that watched a 30-min neutral video (2D documentary) presented on a computer monitor. Assessments of spider fear (Fear of Spiders Questionnaire [FSQ], Behavioral Approach Task [BAT], & subjective ratings of fear) were completed pre- and post-treatment. Consistent with prediction, the stereoscopic 3D video condition outperformed the control condition in reducing fear of spiders showing a large between-group effect size on the FSQ (Cohen's d = 0.85) and a medium between group effect size on the BAT (Cohen's d = 0.47). This provides initial support for stereoscopic 3D video in treating phobias.
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| 50. |
- Minns, Sean, et al.
(author)
-
Immersive 3D exposure-based treatment for spider fear : A randomized controlled trial
- 2019
-
In: Journal of Anxiety Disorders. - : Elsevier BV. - 0887-6185 .- 1873-7897. ; 61, s. 37-44
-
Journal article (peer-reviewed)abstract
- Stereoscopic 3D gives the viewer the same shape, size, perspective and depth they would experience viewing the real world and could mimic the perceptual threat cues present in real life. This is the first study to investigate whether an immersive stereoscopic 3D video exposure-based treatment would be effective in reducing fear of spiders. Participants with a fear of spiders (N = 77) watched two psychoeducational videos with facts about spiders and phobias. They were then randomized to a treatment condition that watched a single session of a stereoscopic 3D immersive video exposure-based treatment (six 5-minute exposures) delivered through a virtual reality headset or a psychoeducation only control condition that watched a 30-minute neutral video (2D documentary) presented on a computer monitor. Assessments of spider fear (Fear of Spiders Questionnaire [FSQ], Behavioral Approach Task [BAT], & subjective ratings of fear) were completed pre- and post-treatment. Consistent with prediction, the stereoscopic 3D video condition outperformed the control condition in reducing fear of spiders showing a large between-group change effect size on the FSQ (Cohen's d = 0.85) and a medium between-group effect size on the BAT (Cohen's d = 0.47). This provides initial support for stereoscopic 3D video in treating phobias.
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