| 1. |
- Mann, P. J., et al.
(författare)
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The biogeochemistry of carbon across a gradient of streams and rivers within the Congo Basin
- 2014
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Ingår i: Journal of Geophysical Research: Biogeosciences. - 2169-8953. ; 119:4, s. 687-702
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Tidskriftsartikel (refereegranskat)abstract
- Dissolved organic carbon (DOC) and inorganic carbon (DIC, pCO(2)), lignin biomarkers, and theoptical properties of dissolved organic matter (DOM) were measured in a gradient of streams and rivers within the Congo Basin, with the aim of examining how vegetation cover and hydrology influences the composition and concentration of fluvial carbon (C). Three sampling campaigns (February 2010, November 2010, and August 2011) spanning 56 sites are compared by subbasin watershed land cover type (savannah, tropical forest, and swamp) and hydrologic regime (high, intermediate, and low). Land cover properties predominately controlled the amount and quality of DOC, chromophoric DOM (CDOM) and lignin phenol concentrations (Sigma(8)) exported in streams and rivers throughout the Congo Basin. Higher DIC concentrations and changing DOM composition (lower molecular weight, less aromatic C) during periods of low hydrologic flow indicated shifting rapid overland supply pathways in wet conditions to deeper groundwater inputs during drier periods. Lower DOC concentrations in forest and swamp subbasins were apparent with increasing catchment area, indicating enhanced DOC loss with extended water residence time. Surface water pCO(2) in savannah and tropical forest catchments ranged between 2,600 and 11,922 mu atm, with swamp regions exhibiting extremely high pCO(2) (10,598-15,802 mu atm), highlighting their potential as significant pathways for water-air efflux. Our data suggest that the quantity and quality of DOM exported to streams and rivers are largely driven by terrestrial ecosystem structure and that anthropogenic land use or climate change may impact fluvial C composition and reactivity, with ramifications for regional C budgets and future climate scenarios.
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| 2. |
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| 3. |
- Barker, Roger A., et al.
(författare)
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GDNF and Parkinson's Disease : Where Next? A Summary from a Recent Workshop
- 2020
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Ingår i: Journal of Parkinson's Disease. - 1877-7171. ; 10:3, s. 875-891
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Tidskriftsartikel (refereegranskat)abstract
- The concept of repairing the brain with growth factors has been pursued for many years in a variety of neurodegenerative diseases including primarily Parkinson's disease (PD) using glial cell line-derived neurotrophic factor (GDNF). This neurotrophic factor was discovered in 1993 and shown to have selective effects on promoting survival and regeneration of certain populations of neurons including the dopaminergic nigrostriatal pathway. These observations led to a series of clinical trials in PD patients including using infusions or gene delivery of GDNF or the related growth factor, neurturin (NRTN). Initial studies, some of which were open label, suggested that this approach could be of value in PD when the agent was injected into the putamen rather than the cerebral ventricles. In subsequent double-blind, placebo-controlled trials, the most recent reporting in 2019, treatment with GDNF did not achieve its primary end point. As a result, there has been uncertainty as to whether GDNF (and by extrapolation, related GDNF family neurotrophic factors) has merit in the future treatment of PD. To critically appraise the existing work and its future, a special workshop was held to discuss and debate this issue. This paper is a summary of that meeting with recommendations on whether there is a future for this therapeutic approach and also what any future PD trial involving GDNF and other GDNF family neurotrophic factors should consider in its design.
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| 4. |
- Ekblom, Robert, et al.
(författare)
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Female choice and male humoral immune response in the lekking great snipe (Gallinago media)
- 2005
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Ingår i: Behavioral Ecology. - : Oxford University Press (OUP). - 1045-2249 .- 1465-7279. ; 16:2, s. 346-351
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Tidskriftsartikel (refereegranskat)abstract
- Parasites and diseases constitute major evolutionary forces in many natural populations, and thus having an efficient immune defense to resist infections is crucial for many organisms. Properties of the immune response may also influence mate choice decisions in many animals. Theory predicts several advantages for females when choosing males with superior immune systems. These benefits can be both direct (e.g. increased paternal care and reduced disease transmission) and indirect (good genes). We have investigated female choice with respect to antibody response to two novel antigens in males of a lekking bird, the great snipe (Gallinago media). Because of the lek mating system, female choice probably mainly incurs indirect (genetic) rather than direct benefits. Males responded to vaccination with diphtheria and tetanus toxoids by producing specific antibodies to both antigens. Triggering the immune system had no negative impact on display activities or survival. Males that were chosen by females as mates had on average higher antibody response to the tetanus antigen than their neighbors. We did not, however, find any covariance between the strength of the antibody response and male mating success.
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| 5. |
- Fiske, P, et al.
(författare)
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Mating success in lekking males: a meta-analysis
- 1998
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Ingår i: BEHAVIORAL ECOLOGY. - : OXFORD UNIV PRESS INC. - 1045-2249. ; 9:4, s. 328-338
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Traits that are correlated with mating success are likely to be subject to sexual selection. In lekking species, a male's mating success can be estimated as the number of females that he copulates with. Earlier reviews of sexual selection in lekking speci
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| 6. |
- Grenn, Francis P., et al.
(författare)
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The Parkinson's Disease Genome-Wide Association Study Locus Browser
- 2020
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Ingår i: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257.
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Tidskriftsartikel (refereegranskat)abstract
- Background: Parkinson's disease (PD) is a neurodegenerative disease with an often complex component identifiable by genome-wide association studies. The most recent large-scale PD genome-wide association studies have identified more than 90 independent risk variants for PD risk and progression across more than 80 genomic regions. One major challenge in current genomics is the identification of the causal gene(s) and variant(s) at each genome-wide association study locus. The objective of the current study was to create a tool that would display data for relevant PD risk loci and provide guidance with the prioritization of causal genes and potential mechanisms at each locus. Methods: We included all significant genome-wide signals from multiple recent PD genome-wide association studies including themost recent PD risk genome-wide association study, age-at-onset genome-wide association study, progression genome-wide association study, and Asian population PD risk genome-wide association study. We gathered data for all genes 1 Mb up and downstream of each variant to allow users to assess which gene(s) are most associated with the variant of interest based on a set of self-ranked criteria. Multiple databases were queried for each gene to collect additional causal data. Results: We created a PD genome-wide association study browser tool (https://pdgenetics.shinyapps.io/GWASBrowser/) to assist the PD research community with the prioritization of genes for follow-up functional studies to identify potential therapeutic targets. Conclusions: Our PD genome-wide association study browser tool provides users with a useful method of identifying potential causal genes at all known PD risk loci from large-scale PD genome-wide association studies. We plan to update this tool with new relevant data as sample sizes increase and new PD risk loci are discovered.
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| 7. |
- Heckman, Michael G., et al.
(författare)
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Population-specific Frequencies for LRRK2 Susceptibility Variants in the Genetic Epidemiology of Parkinson's Disease (GEO-PD) Consortium
- 2013
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Ingår i: Movement Disorders. - : Wiley. - 0885-3185. ; 28:12, s. 1740-1744
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundVariants within the leucine-rich repeat kinase 2 gene are recognized as the most frequent genetic cause of Parkinson's disease. Leucine-rich repeat kinase 2 variation related to disease susceptibility displays many features that reflect the nature of complex, late-onset sporadic disorders like Parkinson's disease. MethodsThe Genetic Epidemiology of Parkinson's Disease Consortium recently performed the largest genetic association study for variants in the leucine-rich repeat kinase 2 gene across 23 different sites in 15 countries. ResultsHerein, we detail the allele frequencies for the novel risk factors (p.A419V and p.M1646T) and the protective haplotype (p.N551K-R1398H-K1423K) nominated in the original publication. Simple population allele frequencies not only can provide insight into the clinical relevance of specific variants but also can help genetically define patient groups. ConclusionsEstablishing individual patient-based genomic susceptibility profiles that incorporate both risk factors and protective factors will determine future diagnostic and treatment strategies. (c) 2013 International Parkinson and Movement Disorder Society
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| 8. |
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| 11. |
- Lundgren, Markus, et al.
(författare)
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Analgesic antipyretic use among young children in the TEDDY study : No association with islet autoimmunity
- 2017
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Ingår i: BMC Pediatrics. - : Springer Science and Business Media LLC. - 1471-2431. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The use of analgesic antipyretics (ANAP) in children have long been a matter of controversy. Data on their practical use on an individual level has, however, been scarce. There are indications of possible effects on glucose homeostasis and immune function related to the use of ANAP. The aim of this study was to analyze patterns of analgesic antipyretic use across the clinical centers of The Environmental Determinants of Diabetes in the Young (TEDDY) prospective cohort study and test if ANAP use was a risk factor for islet autoimmunity. Methods: Data were collected for 8542 children in the first 2.5 years of life. Incidence was analyzed using logistic regression with country and first child status as independent variables. Holm's procedure was used to adjust for multiplicity of intercountry comparisons. Time to autoantibody seroconversion was analyzed using a Cox proportional hazards model with cumulative analgesic use as primary time dependent covariate of interest. For each categorization, a generalized estimating equation (GEE) approach was used. Results: Higher prevalence of ANAP use was found in the U.S. (95.7%) and Sweden (94.8%) compared to Finland (78.1%) and Germany (80.2%). First-born children were more commonly given acetaminophen (OR 1.26; 95% CI 1.07, 1.49; p = 0.007) but less commonly Non-Steroidal Anti-inflammatory Drugs (NSAID) (OR 0.86; 95% CI 0.78, 0.95; p = 0.002). Acetaminophen and NSAID use in the absence of fever and infection was more prevalent in the U.S. (40.4%; 26.3% of doses) compared to Sweden, Finland and Germany (p < 0.001). Acetaminophen or NSAID use before age 2.5 years did not predict development of islet autoimmunity by age 6 years (HR 1.02, 95% CI 0.99-1.09; p = 0.27). In a sub-analysis, acetaminophen use in children with fever weakly predicted development of islet autoimmunity by age 3 years (HR 1.05; 95% CI 1.01-1.09; p = 0.024). Conclusions: ANAP use in young children is not a risk factor for seroconversion by age 6 years. Use of ANAP is widespread in young children, and significantly higher in the U.S. compared to other study sites, where use is common also in absence of fever and infection.
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| 12. |
- Ross, Owen A., et al.
(författare)
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Association of LRRK2 exonic variants with susceptibility to Parkinson's disease: a case-control study
- 2011
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Ingår i: Lancet Neurology. - 1474-4465. ; 10:10, s. 898-908
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Tidskriftsartikel (refereegranskat)abstract
- Background The leucine-rich repeat kinase 2 gene (LRRK2) harbours highly penetrant mutations that are linked to familial parkinsonism. However, the extent of its polymorphic variability in relation to risk of Parkinson's disease (PD) has not been assessed systematically. We therefore assessed the frequency of LRRK2 exonic variants in individuals with and without PD, to investigate the role of the variants in PD susceptibility. Methods LRRK2 was genotyped in patients with PD and controls from three series (white, Asian, and Arab-Berber) from sites participating in the Genetic Epidemiology of Parkinson's Disease Consortium. Genotyping was done for exonic variants of LRRK2 that were identified through searches of literature and the personal communications of consortium members. Associations with PD were assessed by use of logistic regression models. For variants that had a minor allele frequency of 0.5% or greater, single variant associations were assessed, whereas for rarer variants information was collapsed across variants. Findings 121 exonic LRRK2 variants were assessed in 15 540 individuals: 6995 white patients with PD and 5595 controls, 1376 Asian patients and 962 controls, and 240 Arab-Berber patients and 372 controls. After exclusion of carriers of known pathogenic mutations, new independent risk associations were identified for polymorphic variants in white individuals (M1646T, odds ratio 1.43, 95% CI 1.15-1.78; p=0.0012) and Asian individuals (A419V, 2.27, 1.35-3.83; p=0.0011). A protective haplotype (N551K-R1398H-K1423K) was noted at a frequency greater than 5% in the white and Asian series, with a similar finding in the Arab-Berber series (combined odds ratio 0.82, 0.72-0.94; p=0.0043). Of the two previously reported Asian risk variants, G2385R was associated with disease (1.73, 1.20-2.49; p=0.0026), but no association was noted for R1628P (0.62, 0.36-1.07; p=0.087). In the Arab-Berber series, Y2189C showed potential evidence of risk association with PD (4.48, 133-15.09; p=0.012). Interpretation The results for LRRK2 show that several rare and common genetic variants in the same gene can have independent effects on disease risk. LRRK2, and the pathway in which it functions, is important in the cause and pathogenesis of PD in a greater proportion of patients with this disease than previously believed. These results will help discriminate those patients who will benefit most from therapies targeted at LRRK2 pathogenic activity. Funding Michael J Fox Foundation and National Institutes of Health.
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| 13. |
- Saether, Stein Are, et al.
(författare)
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Inferring local adaptation from QST-FST comparisons : neutral genetic and quantitative trait variation in European populations of great snipe
- 2007
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Ingår i: Journal of Evolutionary Biology. - : Wiley. - 1010-061X .- 1420-9101. ; 20:4, s. 1563-1576
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Tidskriftsartikel (refereegranskat)abstract
- We applied a phenotypic QST (PST) vs. FST approach to study spatial variation in selection among great snipe (Gallinago media) populations in two regions of northern Europe. Morphological divergence between regions was high despite low differentiation in selectively neutral genetic markers, whereas populations within regions showed very little neutral divergence and trait differentiation. QST > FST was robust against altering assumptions about the additive genetic proportions of variance components. The homogenizing effect of gene flow (or a short time available for neutral divergence) has apparently been effectively counterbalanced by differential natural selection, although one trait showed some evidence of being under uniform stabilizing selection. Neutral markers can hence be misleading for identifying evolutionary significant units, and adopting the PST–FST approach might therefore be valuable when common garden experiments is not an option. We discuss the statistical difficulties of documenting uniform selection as opposed to divergent selection, and the need for estimating measurement error. Instead of only comparing overall QST and FST values, we advocate the use of partial matrix permutation tests to analyse pairwise QST differences among populations, while statistically controlling for neutral differentiation.
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| 14. |
- Saether, SA, et al.
(författare)
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Male mate choice, sexual conflict and strategic allocation of copulations in a lekking bird
- 2001
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Ingår i: PROCEEDINGS OF THE ROYAL SOCIETY OF LONDON SERIES B-BIOLOGICAL SCIENCES. - : ROYAL SOC LONDON. - 0962-8452. ; 268:1481, s. 2097-2102
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Tidskriftsartikel (refereegranskat)abstract
- The males of lekking species are not expected to be choosy about mating because a reduced reproductive rate due to lost mating opportunities should outweigh any benefits of male choice. Females have traditionally not been expected to be competitive in thi
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| 15. |
- Vehik, Kendra, et al.
(författare)
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Methods, quality control and specimen management in an international multicentre investigation of type 1 diabetes: TEDDY
- 2013
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Ingår i: Diabetes/Metabolism Research & Reviews. - : Wiley. - 1520-7552. ; 29:7, s. 557-567
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe vast array and quantity of longitudinal samples collected in The Environmental Determinants of Diabetes in the Young study present a series of challenges in terms of quality control procedures and data validity. To address this, pilot studies have been conducted to standardize and enhance both biospecimen collection and sample obtainment in terms of autoantibody collection, stool sample preservation, RNA, biomarker stability, metabolic biomarkers and T-cell viability. Research Design and MethodsThe Environmental Determinants of Diabetes in the Young is a multicentre, international prospective study (n=8677) designed to identify environmental triggers of type 1 diabetes (T1D) in genetically at-risk children from ages 3months until 15years. The study is conducted through six primary clinical centres located in four countries. ResultsAs of May 2012, over three million biological samples and 250 million total data points have been collected, which will be analysed to assess autoimmunity status, presence of inflammatory biomarkers, genetic factors, exposure to infectious agents, dietary biomarkers and other potentially important environmental exposures in relation to autoimmunity and progression to T1D. ConclusionsDetailed procedures were utilized to standardize both data harmonization and management when handling a large quantity of longitudinal samples obtained from multiple locations. In addition, a description of the available specimens is provided that serve as an invaluable repository for the elucidation of determinants in T1D focusing on autoantibody concordance and harmonization, transglutaminase autoantibody, inflammatory biomarkers (T-cells), genetic proficiency testing, RNA lab internal quality control testing, infectious agents (monitoring cross-contamination, virus preservation and nasal swab collection validity) and HbA(1c) testing. Copyright (c) 2013 John Wiley & Sons, Ltd.
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