A multi-isotope approach to evaluate the potential of great cormorant eggs for contaminant monitoring

Contaminant monitoring in biota is important for determining environmental status and to detect or prioritize action on hazardous substances. Predators higher up a food chain are often used for monitoring of contaminants that bioaccumulate. However, it is not always possible to find higher predators that are both abundant and have a wide distribution for national or international contaminant monitoring. Great cormorants (Phalocrocorax carbo) are a widespread and increasingly common top predator of fish in fresh, brackish and salt water. We evaluate the suitability of great cormorant eggs as a matrix for contaminant monitoring by using stable isotopes of carbon, nitrogen and sulfur. Despite the fact that cormorants are migratory, egg isotope values showed a significant separation between five breeding colonies in Sweden (1 fresh water lake, 3 Baltic sites and 1 marine site). This high degree of separation indicates that eggs are primarily produced using local resources (not stored body resources) and that contaminants (mercury concentrations in this study) measured in eggs likely reflect levels in fish prey caught close to the breeding area. Compound specific stable isotope analysis was used to estimate cormorant trophic position (TP) and concentrations of mercury in eggs were positively related to TP. The results show that a multi-isotope approach, combined with good ecological diet knowledge allow for meaningful and comparative interpretation of mercury concentrations in biota and that great cormorant eggs appear a suitable matrix to measure locally derived and maternally transferred contaminants

Genome-Wide Association Study and Gene Expression Analysis Identifies CD84 as a Predictor of Response to Etanercept Therapy in Rheumatoid Arthritis

Anti-tumor necrosis factor alpha (anti-TNF) biologic therapy is a widely used treatment for rheumatoid arthritis (RA). It is unknown why some RA patients fail to respond adequately to anti-TNF therapy, which limits the development of clinical biomarkers to predict response or new drugs to target refractory cases. To understand the biological basis of response to anti-TNF therapy, we conducted a genome-wide association study (GWAS) meta-analysis of more than 2 million common variants in 2,706 RA patients from 13 different collections. Patients were treated with one of three anti-TNF medications: etanercept (n = 733), infliximab (n = 894), or adalimumab (n = 1,071). We identified a SNP (rs6427528) at the 1q23 locus that was associated with change in disease activity score (ΔDAS) in the etanercept subset of patients (P = 8×10-8), but not in the infliximab or adalimumab subsets (P>0.05). The SNP is predicted to disrupt transcription factor binding site motifs in the 3′ UTR of an immune-related gene, CD84, and the allele associated with better response to etanercept was associated with higher CD84 gene expression in peripheral blood mononuclear cells (P = 1×10-11 in 228 non-RA patients and P = 0.004 in 132 RA patients). Consistent with the genetic findings, higher CD84 gene expression correlated with lower cross-sectional DAS (P = 0.02, n = 210) and showed a non-significant trend for better ΔDAS in a subset of RA patients with gene expression data (n = 31, etanercept-treated). A small, multi-ethnic replication showed a non-significant trend towards an association among etanercept-treated RA patients of Portuguese ancestry (n = 139, P = 0.4), but no association among patients of Japanese ancestry (n = 151, P = 0.8). Our study demonstrates that an allele associated with response to etanercept therapy is also associated with CD84 gene expression, and further that CD84 expression correlates with disease activity. These findings support a model in which CD84 genotypes and/or expression may serve as a useful biomarker for response to etanercept treatment in RA patients of European ancestry. © 2013 Cui et al

Polychaete invader enhances resource utilization in a species-poor system

Ecosystem consequences of biodiversity change are often studied from a species loss perspective, while the effects of invasive species on ecosystem functions are rarely quantified. In this experimental study, we used isotope tracers to measure the incorporation and burial of carbon and nitrogen from a simulated spring phytoplankton bloom by communities of one to four species of deposit-feeding macrofauna found in the species-poor Baltic Sea. The recently invading polychaete Marenzelleriaarctia, which has spread throughout the Baltic Sea, grows more rapidly than the native species Monoporeia affinis, Pontoporeia femorata (both amphipods) and Macoma balthica (a bivalve), resulting in higher biomass increase (biomass production) in treatments including the polychaete. Marenzelleria incorporated and buried bloom material at rates similar to the native species. Multi-species treatments generally had higher isotope incorporation, indicative of utilization of bloom material, than expected from monoculture yields of the respective species. The mechanism behind this observed over-yielding was mainly niche complementarity in utilization of the bloom input, and was more evident in communities including the invader. In contrast, multi-species treatments had generally lower biomass increase than expected. This contrasting pattern suggests that there is little overlap in resource use of freshly deposited bloom material between Marenzelleria and the native species but it is likely that interference competition acts to dampen resulting community biomass. In conclusion, an invasive species can enhance incorporation and burial of organic matter from settled phytoplankton blooms, two processes fundamental for marine productivity

A Stronger Innate Immune Response During Hyperacute Human Immunodeficiency Virus Type 1 (HIV-1) Infection Is Associated With Acute Retroviral Syndrome.

BACKGROUND: Acute retroviral syndrome (ARS) is associated with human immunodeficiency virus type 1 (HIV-1) subtype and disease progression, but the underlying immunopathological pathways are poorly understood. We aimed to elucidate associations between innate immune responses during hyperacute HIV-1 infection (hAHI) and ARS. METHODS: Plasma samples obtained from volunteers (≥18.0 years) before and during hAHI, defined as HIV-1 antibody negative and RNA or p24 antigen positive, from Kenya, Rwanda, Uganda, Zambia, and Sweden were analyzed. Forty soluble innate immune markers were measured using multiplexed assays. Immune responses were differentiated into volunteers with stronger and comparatively weaker responses using principal component analysis. Presence or absence of ARS was defined based on 11 symptoms using latent class analysis. Logistic regression was used to determine associations between immune responses and ARS. RESULTS: Of 55 volunteers, 31 (56%) had ARS. Volunteers with stronger immune responses (n = 36 [65%]) had increased odds of ARS which was independent of HIV-1 subtype, age, and risk group (adjusted odds ratio, 7.1 [95% confidence interval {CI}: 1.7-28.8], P = .003). Interferon gamma-induced protein (IP)-10 was 14-fold higher during hAHI, elevated in 7 of the 11 symptoms and independently associated with ARS. IP-10 threshold >466.0 pg/mL differentiated stronger immune responses with a sensitivity of 84.2% (95% CI: 60.4-96.6) and specificity of 100.0% (95% CI]: 90.3-100.0). CONCLUSIONS: A stronger innate immune response during hAHI was associated with ARS. Plasma IP-10 may be a candidate biomarker of stronger innate immunity. Our findings provide further insights on innate immune responses in regulating ARS and may inform the design of vaccine candidates harnessing innate immunity

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

Quantification of HIV-2 DNA in Whole Blood

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Hospitalized frail elderly patients - atrial fibrillation, anticoagulation and 12 months outcomes

Background and objective: Multiple chronic conditions and recurring acute illness are frequent among elderly people. One such condition is atrial fibrillation (AF), which increases the risk of stroke up to fivefold. The aim of this study was to investigate the prevalence of AF among hospitalized frail elderly patients, their use of anticoagulation and their 12-month outcomes. Patients and methods: This was a clinical observational study of acutely hospitalized frail patients over the age of 75 years. The CHA2DS2-VASc Score was used to evaluate ischemic stroke risk in patients with AF. Clinically relevant outcomes were the composite of ischemic stroke and/or bleeding within 12 months, which was considered as primary in the analysis, ischemic stroke/transient ischemic attack (TIA), mortality, bleeding and hospital care consumption. Students (test, Fishers exact test, Mann Whitney U test and a Cox proportional hazards model were used for the analyses. Results: The prevalence of AF was 47%, and 63% of them were prescribed an anticoagulant. AF patients without anticoagulation were older, more often females, more often in residential care, and they had worse Mini Nutritional Assessment and activities of daily living scores. Of the patients without anticoagulation, 56% had a documented contraindication. In univariate analysis, there were significantly more events among AF patients without anticoagulation regarding the composite outcome of ischemic stroke and/or bleeding (hazard ratio [1112] 3.65, 95% CI = 1.70-7.86; p amp;lt; 0.001). When adjusting for potential confounders in Cox regression analysis, the difference remained significant (HR 4.54, 95% CI = 1.83-11.25; p = 0.001). Conclusion: The prevalence of AF in a hospitalized frail elderly population was 47%. Of these, 63% were prescribed anticoagulation therapy. Almost half of the patients without stroke pro-phylaxis had no documented contraindication. At 1 year, there were significantly more events in terms of ischemic stroke and/or bleeding among AF patients without anticoagulation therapy than among those with.Funding Agencies|Healthcare sub-committee, Region Vastra Gotaland, Sweden; Department of Research and Development, NU Hospital Group, Sweden; Fyrbodal Research and Development Council, Region Vastra Gotaland, Sweden</p

HIV-2 Neutralization Sensitivity in Relation to Co-Receptor Entry Pathways and Env Motifs

HIV-2, compared to HIV-1, elicits potent and broadly neutralizing antibodies, and uses a broad range of co-receptors. However, both sensitivity to neutralization and breadth of co-receptor use varies between HIV-2 isolates, and the molecular background is still not fully understood. Thus, in the current study, we have deciphered relationships between HIV-2 neutralization sensitivity, co-receptor use and viral envelope glycoprotein (Env) molecular motifs. A panel of primary HIV-2 isolates, with predefined use of co-receptors, was assessed for neutralization sensitivity using a set of HIV-2 Env-directed monoclonal antibodies and co-receptor indicator cell lines. Neutralization sensitivity of the isolates was analysed in relation target cell co-receptor expression, in addition to amino acid motifs and predicted structures of Env regions. Results showed that HIV-2 isolates were more resistant to neutralizing antibodies when entering target cells via the alternative co-receptor GPR15, as compared to CCR5. A similar pattern was noted for isolates using the alternative co-receptor CXCR6. Sensitivity to neutralizing antibodies appeared also to be linked to specific Env motifs in V1/V2 and C3 regions. Our findings suggest that HIV-2 sensitivity to neutralization depends both on which co-receptor is used for cell entry and on specific Env motifs. This study highlights the multifactorial mechanisms behind HIV-2 neutralization sensitivity