Temporal change in phytoplankton diversity and functional group composition

One of the key challenges in managing eutrophication in coastal marine ecosystems is the harmonized cross-border assessment of phytoplankton. Some general understanding of the consequences of shifting nutrient regimes can be derived from the detailed investigation of the phytoplankton community and its biodiversity. Here, we combined long-term monitoring datasets of German and Dutch coastal stations and amended these with additional information on species biomass. Across the integrated and harmonized dataset, we used multiple biodiversity descriptors to analyse temporal trends in the Wadden Sea phytoplankton. Biodiversity, measured as the number of species (S) and the effective number of species (ENS), has decreased in the Dutch stations over the last 20 years, while biomass has increased, indicating that fewer species are becoming more dominant in the system. However, biodiversity and biomass did not show substantial changes in the German stations. Although there were some differences in trends between countries, shifts in community composition and relative abundance were consistent across stations and time. We emphasise the importance of continuous and harmonized monitoring programmes and multi-metric approaches that can detect changes in the communities that are indicative of changes in the environment

Immunogenicity, safety, and efficacy of the HPV vaccines among people living with HIV: A systematic review and meta-analysis

Background: Vaccines have been demonstrated to protect against high-risk human papillomavirus infection (HPV), including HPV-16/18, and cervical lesions among HIV negative women. However, their efficacy remains uncertain for people living with HIV (PLHIV).We systematically reviewed available evidence on HPV vaccine on immunological, virological, or other biological outcomes in PLHIV. Methods: We searched five electronic databases (PubMed, Medline and Embase, clinicaltrials.gov and the WHO clinical trial database) for longitudinal prospective studies reporting immunogenicity, virological, cytological, histological, clinical or safety endpoints following prophylactic HPV vaccination among PLHIV. We included studies published by February 11th, 2021. We summarized results, assessed study quality, and conducted meta-analysis and subgroup analyses, where possible. Findings: We identified 43 publications stemming from 18 independent studies (Ns =18), evaluating the quadrivalent (Ns =15), bivalent (Ns =4) and nonavalent (Ns =1) vaccines. A high proportion seroconverted for the HPV vaccine types. Pooled proportion seropositive by 28 weeks following 3 doses with the bivalent, quadrivalent, and nonavalent vaccines were 0.99 (95% confidence interval: 0.95-1.00, Ns =1), 0.99 (0.98-1.00, Ns =9), and 1.00 (0.99-1.00, Ns =1) for HPV-16 and 0.99 (0.96-1.00, Ns =1), 0.94 (0.91-0.96, Ns =9), and 1.00 (0.99-1.00, Ns =1) for HPV-18, respectively. Seropositivity remained high among people who received 3 doses despite some declines in antibody titers and lower seropositivity over time, especially for HPV-18, for the quadrivalent than the bivalent vaccine, and for HIV positive than negative individuals. Seropositivity for HPV-18 at 29-99 weeks among PLHIV was 0.72 (0.66-0.79, Ns =8) and 0.96 (0.92-0.99, Ns =2) after 3 doses of the quadrivalent and bivalent vaccine, respectively and 0.94 (0.90-0.98, Ns =3) among HIV-negative historical controls. Evidence suggests that the seropositivity after vaccination declines over time but it can lasts at least 2-4 years. The vaccines were deemed safe among PLHIV with few serious adverse events. Evidence of HPV vaccine efficacy against acquisition of HPV infection and/or associated disease from the eight trials available was inconclusive due to the low quality. Interpretation: PLHIV have a robust and safe immune response to HPV vaccination. Antibody titers and seropositivity rates decline over time but remain high. The lack of a formal correlate of protection and efficacy results preclude definitive conclusions on the clinical benefits. Nevertheless, given the burden of HPV disease in PLHIV, although the protection may be shorter or less robust against HPV-18, the robust immune response suggests that PLHIV may benefit from receiving HPV vaccination after acquiring HIV. Better quality studies are needed to demonstrate the clinical efficacy among PLHIV. Funding: World Health Organization. MRC Centre for Global Infectious Disease Analysis, Canadian Institutes of Health Research, UK Medical Research Council (MRC)

Epigenetic regulation of PPARGC1A in human type 2 diabetic islets and effect on insulin secretion

Aims/hypothesis Insulin secretion in pancreatic islets is dependent upon mitochondrial function and production of ATP. The transcriptional coactivator peroxisome proliferator activated receptor gamma coactivator-1 alpha (protein PGC-1 alpha; gene PPARGC1A) is a master regulator of mitochondrial genes and its expression is decreased and related to impaired oxidative phosphorylation in muscle from patients with type 2 diabetes. Whether it plays a similar role in human pancreatic islets is not known. We therefore investigated if PPARGC1A expression is altered in islets from patients with type 2 diabetes and whether this expression is influenced by genetic (PPARGC1A Gly482Ser polymorphism) and epigenetic (DNA methylation) factors. We also tested if experimental downregulation of PPARGC1A expression in human islets influenced insulin secretion. Methods The PPARGC1A Gly482Ser polymorphism was genotyped in human pancreatic islets from 48 non-diabetic and 12 type 2 diabetic multi-organ donors and related to PPARGC1A mRNA expression. DNA methylation of the PPARGC1A promoter was analysed in pancreatic islets from ten type 2 diabetic and nine control donors. Isolated human islets were transfected with PPARGC1A silencing RNA (siRNA). Results PPARGC1A mRNA expression was reduced by 90% (p < 0.005) and correlated with the reduction in insulin secretion in islets from patients with type 2 diabetes. After downregulation of PPARGC1A expression in human islets by siRNA, insulin secretion was reduced by 41% (p <= 0. 01). We were able to ascribe reduced PPARGC1A expression in islets to both genetic and epigenetic factors, i.e. a common PPARGC1A Gly482Ser polymorphism was associated with reduced PPARGC1A mRNA expression (p < 0.00005) and reduced insulin secretion (p < 0.05). In support of an epigenetic influence, the PPARGC1A gene promoter showed a twofold increase in DNA methylation in diabetic islets compared with non-diabetic islets (p < 0.04). Conclusions/Interpretation We have shown for the first time that PPARGC1A might be important in human islet insulin secretion and that expression of PPARGC1A in human islets can be regulated by both genetic and epigenetic factors

(Micro)evolutionary changes and the evolutionary potential of bird migration

Seasonal migration is the yearly long-distance movement of individuals between their breeding and wintering grounds. Individuals from nearly every animal group exhibit this behavior, but probably the most iconic migration is carried out by birds, from the classic V-shape formation of geese on migration to the amazing nonstop long-distance flights undertaken by Arctic Terns Sterna paradisaea. In this chapter, we discuss how seasonal migration has shaped the field of evolution. First, this behavior is known to turn on and off quite rapidly, but controversy remains concerning where this behavior first evolved geographically and whether the ancestral state was sedentary or migratory (Fig. 7.1d, e). We review recent work using new analytical techniques to provide insight into this topic. Second, it is widely accepted that there is a large genetic basis to this trait, especially in groups like songbirds that migrate alone and at night precluding any opportunity for learning. Key hypotheses on this topic include shared genetic variation used by different populations to migrate and only few genes being involved in its control. We summarize recent work using new techniques for both phenotype and genotype characterization to evaluate and challenge these hypotheses. Finally, one topic that has received less attention is the role these differences in migratory phenotype could play in the process of speciation. Specifically, many populations breed next to one another but take drastically different routes on migration (Fig. 7.2). This difference could play an important role in reducing gene flow between populations, but our inability to track most birds on migration has so far precluded evaluations of this hypothesis. The advent of new tracking techniques means we can track many more birds with increasing accuracy on migration, and this work has provided important insight into migration's role in speciation that we will review here

Association of Genetic Variants of Melatonin Receptor 1B with Gestational Plasma Glucose Level and Risk of Glucose Intolerance in Pregnant Chinese Women

BACKGROUND: This study aimed to explore the association of MTNR1B genetic variants with gestational plasma glucose homeostasis in pregnant Chinese women. METHODS: A total of 1,985 pregnant Han Chinese women were recruited and evaluated for gestational glucose tolerance status with a two-step approach. The four MTNR1B variants rs10830963, rs1387153, rs1447352, and rs2166706 which had been reported to associate with glucose levels in general non-pregnant populations, were genotyped in these women. Using an additive model adjusted for age and body mass index (BMI), association of these variants with gestational fasting and postprandial plasma glucose (FPG and PPG) levels were analyzed by multiple linear regression; relative risk of developing gestational glucose intolerance was calculated by logistic regression. Hardy-Weinberg Equilibrium was tested by Chi-square and linkage disequilibrium (LD) between these variants was estimated by measures of D' and r(2). RESULTS: In the pregnant Chinese women, the MTNR1B variant rs10830963, rs1387153, rs2166706 and rs1447352 were shown to be associated with the increased 1 hour PPG level (p=8.04 × 10(-10), 5.49 × 10(-6), 1.89 × 10(-5) and 0.02, respectively). The alleles were also shown to be associated with gestational glucose intolerance with odds ratios (OR) of 1.64 (p=8.03 × 10(-11)), 1.43 (p=1.94 × 10(-6)), 1.38 (p=1.63 × 10(-5)) and 1.24 (p=0.007), respectively. MTNR1B rs1387153, rs2166706 were shown to be associated with gestational FPG levels (p=0.04). Our data also suggested that, the LD pattern of these variants in the studied women conformed to that in the general populations: rs1387153 and rs2166706 were in high LD, they linked moderately with rs10830963, but might not linked with rs1447352;rs10830963 might not link with rs1447352, either. In addition, the MTNR1B variants were not found to be associated with any other traits tested. CONCLUSIONS: The MTNR1B is likely to be involved in the regulation of glucose homeostasis during pregnancy

Virtual screening and evaluation of Ketol-Acid Reducto-Isomerase (KARI) as a putative drug target for Aspergillosis

Aspergillus is a leading causative agent for fungal morbidity and mortality in immuno-compromised patients. To identify a putative target to design or identify new antifungal drug, against Aspergillus is required. In our previous work, we have analyzed the various biochemical pathways, and we found Ketol Acid Reducto-Isomerase (KARI) an enzyme involves in the amino acid biosynthesis, could be a better target. This enzyme was found to be unique by comparing to host proteome through BLASTp analysis. A homology based model of KARI was generated by Swiss model server. The generated model had been validated by PROCHECK and WHAT IF programs. The Zinc library was generated within the limitation of the Lipinski rule of five, for docking study. Based on the dock-score six molecules have been studied for ADME/TOX analysis and subjected for pharmacophore model generation. The Zinc ID of the potential inhibitors is ZINC00720614, ZINC01068126, ZINC0923, ZINC02090678, ZINC00663057 and ZINC02284065 and found to be pharmacologically active agonist and antagonist of KARI. This study is an attempt to Insilco evaluation of the KARI as a drug target and the screened inhibitors could help in the development of the better drug against Aspergillus

Bayesian reassessment of the epigenetic architecture of complex traits

Linking epigenetic marks to clinical outcomes improves insight into molecular processes, disease prediction, and therapeutic target identification. Here, a statistical approach is presented to infer the epigenetic architecture of complex disease, determine the variation captured by epigenetic effects, and estimate phenotype-epigenetic probe associations jointly. Implicitly adjusting for probe correlations, data structure (cell-count or relatedness), and single-nucleotide polymorphism (SNP) marker effects, improves association estimates and in 9,448 individuals, 75.7% (95% CI 71.70–79.3) of body mass index (BMI) variation and 45.6% (95% CI 37.3–51.9) of cigarette consumption variation was captured by whole blood methylation array data. Pathway-linked probes of blood cholesterol, lipid transport and sterol metabolism for BMI, and xenobiotic stimuli response for smoking, showed >1.5 times larger associations with >95% posterior inclusion probability. Prediction accuracy improved by 28.7% for BMI and 10.2% for smoking over a LASSO model, with age-, and tissue-specificity, implying associations are a phenotypic consequence rather than causal

Assessing the potential impact of disruptions due to COVID-19 on HIV among key and lower-risk populations in the largest cities of Cameroon and Benin

Background: The COVID-19 pandemic indirectly impacts HIV epidemiology in Central/West Africa. We estimated the potential impact of COVID-19-related disruptions to HIV prevention/treatment services and sexual partnerships on HIV incidence and HIV-related deaths among key populations including female sex workers (FSW), their clients, men who have sex with men (MSM), and overall. Setting: Yaoundé (Cameroon) and Cotonou (Benin). Methods: We used mathematical models of HIV calibrated to city- and risk-population-specific demographic/behavioural/epidemic data. We estimated the relative change in 1-year HIV incidence and HIV-related deaths for various disruption scenarios of HIV prevention/treatment services and decreased casual/commercial partnerships, compared to a scenario without COVID-19. Results: A 50% reduction in condom use in all partnerships over 6 months would increase 1-year HIV incidence by 39%, 42%, 31% and 23% among MSM, FSW, clients, and overall in Yaoundé respectively, and 69%, 49% and 23% among FSW, clients and overall respectively in Cotonou. Combining a 6-month interruption of ART initiation and 50% reduction in HIV prevention/treatment use would increase HIV incidence by 50% and HIV-related deaths by 20%. This increase in HIV infections would be halved by a simultaneous 50% reduction in casual and commercial partnerships. Conclusions: Reductions in condom use following COVID-19 would increase infections among key populations disproportionately, particularly FSW in Cotonou, who need uninterrupted condom provision. Disruptions in HIV prevention/treatment services have the biggest impacts on HIV infections and deaths overall, only partially mitigated by equal reductions in casual/commercial sexual partnerships. Maintaining ART provision must be prioritised to minimise short-term excess HIV-related deaths

How to find simple and accurate rules for viral protease cleavage specificities

<p>Abstract</p> <p>Background</p> <p>Proteases of human pathogens are becoming increasingly important drug targets, hence it is necessary to understand their substrate specificity and to interpret this knowledge in practically useful ways. New methods are being developed that produce large amounts of cleavage information for individual proteases and some have been applied to extract cleavage rules from data. However, the hitherto proposed methods for extracting rules have been neither easy to understand nor very accurate. To be practically useful, cleavage rules should be accurate, compact, and expressed in an easily understandable way.</p> <p>Results</p> <p>A new method is presented for producing cleavage rules for viral proteases with seemingly complex cleavage profiles. The method is based on orthogonal search-based rule extraction (OSRE) combined with spectral clustering. It is demonstrated on substrate data sets for human immunodeficiency virus type 1 (HIV-1) protease and hepatitis C (HCV) NS3/4A protease, showing excellent prediction performance for both HIV-1 cleavage and HCV NS3/4A cleavage, agreeing with observed HCV genotype differences. New cleavage rules (consensus sequences) are suggested for HIV-1 and HCV NS3/4A cleavages. The practical usability of the method is also demonstrated by using it to predict the location of an internal cleavage site in the HCV NS3 protease and to correct the location of a previously reported internal cleavage site in the HCV NS3 protease. The method is fast to converge and yields accurate rules, on par with previous results for HIV-1 protease and better than previous state-of-the-art for HCV NS3/4A protease. Moreover, the rules are fewer and simpler than previously obtained with rule extraction methods.</p> <p>Conclusion</p> <p>A rule extraction methodology by searching for multivariate low-order predicates yields results that significantly outperform existing rule bases on out-of-sample data, but are more transparent to expert users. The approach yields rules that are easy to use and useful for interpreting experimental data.</p