Responses to projected changes in climate and UV-B at the species level

Environmental manipulation experiments showed that species respond individualistically to each environmental-change variable. The greatest responses of plants were generally to nutrient, particularly nitrogen, addition. Summer warming experiments showed that woody plant responses were dominant and that mosses and lichens became less abundant. Responses to warming were controlled by moisture availability and snow cover. Many invertebrates increased population growth in response to summer warming, as long as desiccation was not induced. CO2 and UV-B enrichment experiments showed that plant and animal responses were small. However, some microorganisms and species of fungi were sensitive to increased UV-B and some intensive mutagenic actions could, perhaps, lead to unexpected epidemic outbreaks. Tundra soil heating, CO 2 enrichment and amendment with mineral nutrients generally accelerated microbial activity. Algae are likely to dominate cyanobacteria in milder climates. Expected increases in winter freeze-thaw cycles leading to ice-crust formation are likely to severely reduce winter survival rate and disrupt the population dynamics of many terrestrial animals. A deeper snow cover is likely to restrict access to winter pastures by reindeer/caribou and their ability to flee from predators while any earlier onset of the snow-free period is likely to stimulate increased plant growth. Initial species responses to climate change might occur at the sub-species level: an Arctic plant or animal species with high genetic/racial diversity has proved an ability to adapt to different environmental conditions in the past and is likely to do so also in the future. Indigenous knowledge, air photographs, satellite images and monitoring show that changes in the distributions of some species are already occurring: Arctic vegetation is becoming more shrubby and more productive, there have been recent changes in the ranges of caribou, and "new" species of insects and birds previously associated with areas south of the treeline have been recorded. In contrast, almost all Arctic breeding bird species are declining and models predict further quite dramatic reductions of the populations of tundra birds due to warming. Species-climate response surface models predict potential future ranges of current Arctic species that are often markedly reduced and displaced northwards in response to warming. In contrast, invertebrates and microorganisms are very likely to quickly expand their ranges northwards into the Arctic

Lymphocyte Subpopulations in Lymph Nodes and Peripheral Blood: A Comparison between Patients with Stable Angina and Acute Coronary Syndrome

Objective: Atherosclerosis is characterized by a chronic inflammatory response involving activated T cells and impairment of natural killer (NK) cells. An increased T cell activity has been associated with plaque instability and risk of acute cardiac events. Lymphocyte analyses in blood are widely used to evaluate the immune status. However, peripheral blood contains only a minor proportion of lymphocytes. In this study, we hypothesized that thoracic lymph nodes from patients with stable angina (SA) and acute coronary syndrome (ACS) might add information to peripheral blood analyses. less thanbrgreater than less thanbrgreater thanMethods: Peripheral blood and lymph nodes were collected during coronary by-pass surgery in 13 patients with SA and 13 patients with ACS. Lymphocyte subpopulations were assessed by flow cytometry using antibodies against CD3, CD4, CD8, CD19, CD16/56, CD25, Foxp3, CD69, HLA-DR, IL-18 receptor (R) and CCR4. less thanbrgreater than less thanbrgreater thanResults: Lymph nodes revealed a lymphocyte subpopulation profile substantially differing from that in blood including a higher proportion of B cells, lower proportions of CD8(+) T cells and NK cells and a 2-fold higher CD4/CD8 ratio. CD4(+)CD69(+) cells as well as Foxp3(+) regulatory T cells were markedly enriched in lymph nodes (p andlt; 0.001) while T helper 1-like (CD4(+)IL-18R(+)) cells were more frequent in blood (p andlt; 0.001). The only significant differences between ACS and SA patients involved NK cells that were reduced in the ACS group. However, despite being reduced, the NK cell fraction in ACS patients contained a significantly higher proportion of IL-18R(+) cells compared with SA patients (p andlt; 0.05). less thanbrgreater than less thanbrgreater thanConclusion: There were several differences in lymphocyte subpopulations between blood and lymph nodes. However, the lymphocyte perturbations in peripheral blood of ACS patients compared with SA patients were not mirrored in lymph nodes. The findings indicate that lymph node analyses in multivessel coronary artery disease may not reveal any major changes in the immune response that are not detectable in blood.Funding Agencies|Swedish Heart-Lung Foundation|20090489|Swedish Research Council|2008-2282

Fourteen sequence variants that associate with multiple sclerosis discovered by meta-analysis informed by genetic correlations

A meta-analysis of publicly available summary statistics on multiple sclerosis combined with three Nordic multiple sclerosis cohorts (21,079 cases, 371,198 controls) revealed seven sequence variants associating with multiple sclerosis, not reported previously. Using polygenic risk scores based on public summary statistics of variants outside the major histocompatibility complex region we quantified genetic overlap between common autoimmune diseases in Icelanders and identified disease clusters characterized by autoantibody presence/absence. As multiple sclerosis-polygenic risk scores captures the risk of primary biliary cirrhosis and vice versa (P = 1.6 x 10(-7), 4.3 x 10(-9)) we used primary biliary cirrhosis as a proxy-phenotype for multiple sclerosis, the idea being that variants conferring risk of primary biliary cirrhosis have a prior probability of conferring risk of multiple sclerosis. We tested 255 variants forming the primary biliary cirrhosis-polygenic risk score and found seven multiple sclerosis-associating variants not correlated with any previously established multiple sclerosis variants. Most of the variants discovered are close to or within immune-related genes. One is a low-frequency missense variant in TYK2, another is a missense variant in MTHFR that reduces the function of the encoded enzyme affecting methionine metabolism, reported to be dysregulated in multiple sclerosis brain.publishedVersio

Fourteen sequence variants that associate with multiple sclerosis discovered by meta-analysis informed by genetic correlations

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked FilesA meta-analysis of publicly available summary statistics on multiple sclerosis combined with three Nordic multiple sclerosis cohorts (21,079 cases, 371,198 controls) revealed seven sequence variants associating with multiple sclerosis, not reported previously. Using polygenic risk scores based on public summary statistics of variants outside the major histocompatibility complex region we quantified genetic overlap between common autoimmune diseases in Icelanders and identified disease clusters characterized by autoantibody presence/absence. As multiple sclerosis-polygenic risk scores captures the risk of primary biliary cirrhosis and vice versa (P = 1.6 x 10(-7), 4.3 x 10(-9)) we used primary biliary cirrhosis as a proxy-phenotype for multiple sclerosis, the idea being that variants conferring risk of primary biliary cirrhosis have a prior probability of conferring risk of multiple sclerosis. We tested 255 variants forming the primary biliary cirrhosis-polygenic risk score and found seven multiple sclerosis-associating variants not correlated with any previously established multiple sclerosis variants. Most of the variants discovered are close to or within immune-related genes. One is a low-frequency missense variant in TYK2, another is a missense variant in MTHFR that reduces the function of the encoded enzyme affecting methionine metabolism, reported to be dysregulated in multiple sclerosis brain.Swedish Research Council Knut and Alice Wallenberg Foundation AFA Foundation Swedish Brain Foundatio

Modelling the Genetic Risk in Age-Related Macular Degeneration

Late-stage age-related macular degeneration (AMD) is a common sight-threatening disease of the central retina affecting approximately 1 in 30 Caucasians. Besides age and smoking, genetic variants from several gene loci have reproducibly been associated with this condition and likely explain a large proportion of disease. Here, we developed a genetic risk score (GRS) for AMD based on 13 risk variants from eight gene loci. The model exhibited good discriminative accuracy, area-under-curve (AUC) of the receiver-operating characteristic of 0.820, which was confirmed in a cross-validation approach. Noteworthy, younger AMD patients aged below 75 had a significantly higher mean GRS (1.87, 95% CI: 1.69–2.05) than patients aged 75 and above (1.45, 95% CI: 1.36–1.54). Based on five equally sized GRS intervals, we present a risk classification with a relative AMD risk of 64.0 (95% CI: 14.11–1131.96) for individuals in the highest category (GRS 3.44–5.18, 0.5% of the general population) compared to subjects with the most common genetic background (GRS −0.05–1.70, 40.2% of general population). The highest GRS category identifies AMD patients with a sensitivity of 7.9% and a specificity of 99.9% when compared to the four lower categories. Modeling a general population around 85 years of age, 87.4% of individuals in the highest GRS category would be expected to develop AMD by that age. In contrast, only 2.2% of individuals in the two lowest GRS categories which represent almost 50% of the general population are expected to manifest AMD. Our findings underscore the large proportion of AMD cases explained by genetics particularly for younger AMD patients. The five-category risk classification could be useful for therapeutic stratification or for diagnostic testing purposes once preventive treatment is available

GWAS of thyroid stimulating hormone highlights pleiotropic effects and inverse association with thyroid cancer

Correction: Volume12, Issue1 Article Number7354 DOI10.1038/s41467-021-27675-w PublishedDEC 16 2021Thyroid stimulating hormone (TSH) is critical for normal development and metabolism. To better understand the genetic contribution to TSH levels, we conduct a GWAS meta-analysis at 22.4 million genetic markers in up to 119,715 individuals and identify 74 genome-wide significant loci for TSH, of which 28 are previously unreported. Functional experiments show that the thyroglobulin protein-altering variants P118L and G67S impact thyroglobulin secretion. Phenome-wide association analysis in the UK Biobank demonstrates the pleiotropic effects of TSH-associated variants and a polygenic score for higher TSH levels is associated with a reduced risk of thyroid cancer in the UK Biobank and three other independent studies. Two-sample Mendelian randomization using TSH index variants as instrumental variables suggests a protective effect of higher TSH levels (indicating lower thyroid function) on risk of thyroid cancer and goiter. Our findings highlight the pleiotropic effects of TSH-associated variants on thyroid function and growth of malignant and benign thyroid tumors. Thyroid stimulating hormone (TSH) is critical for normal development and metabolism. Here, the authors conduct a GWAS and suggest protective effect of higher TSH on risk of thyroid cancer and goitre.Peer reviewe

Author Correction:GWAS of thyroid stimulating hormone highlights the pleiotropic effects and inverse association with thyroid cancer

The original version of this article contained an error in the results, in the second paragraph of the subsection entitled “Fine-mapping for potentially causal variants among TSH loci”, in which effect sizes for two variants were incorrectly reported

GWAS of thyroid stimulating hormone highlights pleiotropic effects and inverse association with thyroid cancer

Thyroid stimulating hormone (TSH) is critical for normal development and metabolism. To better understand the genetic contribution to TSH levels, we conduct a GWAS meta-analysis at 22.4 million genetic markers in up to 119,715 individuals and identify 74 genome-wide significant loci for TSH, of which 28 are previously unreported. Functional experiments show that the thyroglobulin protein-altering variants P118L and G67S impact thyroglobulin secretion. Phenome-wide association analysis in the UK Biobank demonstrates the pleiotropic effects of TSH-associated variants and a polygenic score for higher TSH levels is associated with a reduced risk of thyroid cancer in the UK Biobank and three other independent studies. Two-sample Mendelian randomization using TSH index variants as instrumental variables suggests a protective effect of higher TSH levels (indicating lower thyroid function) on risk of thyroid cancer and goiter. Our findings highlight the pleiotropic effects of TSH-associated variants on thyroid function and growth of malignant and benign thyroid tumors

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Does Aerobic Exercise Influence Intrinsic Brain Activity? An Aerobic Exercise Intervention among Healthy Old Adults

Previous studies have indicated that aerobic exercise could reduce age related decline in cognition and brain functioning. Here we investigated the effects of aerobic exercise on intrinsic brain activity. Sixty sedentary healthy males and females (64–78 years) were randomized into either an aerobic exercise group or an active control group. Both groups recieved supervised training, 3 days a week for 6 months. Multimodal brain imaging data was acquired before and after the intervention, including 10 min of resting state brain functional magnetic resonance imaging (rs-fMRI) and arterial spin labeling (ASL). Additionally, a comprehensive battery of cognitive tasks assessing, e.g., executive function and episodic memory was administered. Both the aerobic and the control group improved in aerobic capacity (VO2-peak) over 6 months, but a significant group by time interaction confirmed that the aerobic group improved more. Contrary to our hypothesis, we did not observe any significant group by time interactions with regard to any measure of intrinsic activity. To further probe putative relationships between fitness and brain activity, we performed post hoc analyses disregarding group belongings. At baseline, VO2-peak was negativly related to BOLD-signal fluctuations (BOLDSTD) in mid temporal areas. Over 6 months, improvements in aerobic capacity were associated with decreased connectivity between left hippocampus and contralateral precentral gyrus, and positively to connectivity between right mid-temporal areas and frontal and parietal regions. Independent component analysis identified a VO2-related increase in coupling between the default mode network and left orbitofrontal cortex, as well as a decreased connectivity between the sensorimotor network and thalamus. Extensive exploratory data analyses of global efficiency, connectome wide multivariate pattern analysis (connectome-MVPA), as well as ASL, did not reveal any relationships between aerobic fitness and intrinsic brain activity. Moreover, fitness-predicted changes in functional connectivity did not relate to changes in cognition, which is likely due to absent cross-sectional or longitudinal relationships between VO2-peak and cognition. We conclude that the aerobic exercise intervention had limited influence on patterns of intrinsic brain activity, although post hoc analyses indicated that individual changes in aerobic capacity preferentially influenced mid-temporal brain areas