Lipidation of Pneumococcal Antigens Leads to Improved Immunogenicity and Protection

Streptococcus pneumoniaeinfections lead to high morbidity and mortality rates worldwide.Pneumococcal polysaccharide conjugate vaccines significantly reduce the burden of disease but havea limited range of protection, which encourages the development of a broadly protective protein-basedalternative. We and others have shown that immunization with pneumococcal lipoproteins that lackthe lipid anchor protects against colonization. Since immunity againstS. pneumoniaeis mediatedthrough Toll-like receptor 2 signaling induced by lipidated proteins, we investigated the effects ofa lipid modification on the induced immune responses in either intranasally or subcutaneouslyvaccinated mice. Here, we demonstrate that lipidation of recombinant lipoproteins DacB and PnrAstrongly improves their immunogenicity. Mice immunized with lipidated proteins showed enhancedantibody concentrations and different induction kinetics. The induced humoral immune responsewas modulated by lipidation, indicated by increased IgG2/IgG1 subclass ratios related to Th1-typeimmunity. In a mouse model of colonization, immunization with lipidated antigens led to a moderatebut consistent reduction of pneumococcal colonization as compared to the non-lipidated proteins,indicating that protein lipidation can improve the protective capacity of the coupled antigen. Thus,protein lipidation represents a promising approach for the development of a serotype-independentpneumococcal vaccine

Metabolic effects of early life stress and pre-pregnancy obesity are long lasting and sex specific in mice

Early life stress (ELS) is associated with metabolic, cognitive, and psychiatric diseases and has a very high prevalence, highlighting the urgent need for a better understanding of the versatile physiological changes and identification of predictive biomarkers. In addition to programming the hypothalamic-pituitary-adrenal (HPA) axis, ELS may also affect the gut microbiota and metabolome, opening up a promising research direction for identifying early biomarkers of ELS-induced (mal)adaptation. Other factors affecting these parameters include maternal metabolic status and diet, with maternal obesity shown to predispose offspring to later metabolic disease. The aim of the present study was to investigate the long-term effects of ELS and maternal obesity on the metabolic and stress phenotype of rodent offspring. To this end, offspring of both sexes were subjected to an adverse early-life experience, and their metabolic and stress phenotypes were examined. In addition, we assessed whether a prenatal maternal and an adult high-fat diet (HFD) stressor further shape observed ELS-induced phenotypes. We show that ELS has long-term effects on male body weight (BW) across the lifespan, whereas females more successfully counteract ELS-induced weight loss, possibly by adapting their microbiota, thereby stabilizing a balanced metabolome. Furthermore, the metabolic effects of a maternal HFD on BW are exclusively triggered by a dietary challenge in adult offspring and are more pronounced in males than in females. Overall, our study suggests that the female microbiota protects against an ELS challenge, rendering them more resilient to additional maternal- and adult nutritional stressors than males.This work was supported by the “GUTMOM” grant of the ERA-Net Cofund HDHL-INTIMIC (INtesTInal MIcrobiomics) under the JPI HDHL (Joint Programming Initiative – A healthy diet for a healthy life) umbrella (01EA1805; MVS), the SCHM2360-5-1 grant (MVS) from the German Research Foundation (DFG), the ZonMw grant from the Netherlands Organisation for Health Research and Development (project number 529051019), the DIM-ELI-2 grant of La Fundación La Marató-TV3 (ref. 2018-27/30-31), the PID2019-108973RB-C22 and PCIN2017-117 grants from the Ministerio de Ciencia e Innovación of Spain and the grants GV/2020/048 and IDIFEDER/2021/072 from the Generalitat Valenciana of Spain. Open Access funding enabled and organized by Projekt DEAL.Peer reviewe

Computational approaches for network-based integrative multi-omics analysis

Advances in omics technologies allow for holistic studies into biological systems. These studies rely on integrative data analysis techniques to obtain a comprehensive view of the dynamics of cellular processes, and molecular mechanisms. Network-based integrative approaches have revolutionized multi-omics analysis by providing the framework to represent interactions between multiple different omics-layers in a graph, which may faithfully reflect the molecular wiring in a cell. Here we review network-based multi-omics/multi-modal integrative analytical approaches. We classify these approaches according to the type of omics data supported, the methods and/or algorithms implemented, their node and/or edge weighting components, and their ability to identify key nodes and subnetworks. We show how these approaches can be used to identify biomarkers, disease subtypes, crosstalk, causality, and molecular drivers of physiological and pathological mechanisms. We provide insight into the most appropriate methods and tools for research questions as showcased around the aetiology and treatment of COVID-19 that can be informed by multi-omics data integration. We conclude with an overview of challenges associated with multi-omics network-based analysis, such as reproducibility, heterogeneity, (biological) interpretability of the results, and we highlight some future directions for network-based integration

Novel high-resolution targeted sequencing of the cervicovaginal microbiome

BACKGROUND: The cervicovaginal microbiome (CVM) plays a significant role in women's cervical health and disease. Microbial alterations at the species level and characteristic community state types (CST) have been associated with acquisition and persistence of high-risk human papillomavirus (hrHPV) infections that may result in progression of cervical lesions to malignancy. Current sequencing methods, especially most commonly used multiplex 16S rRNA gene sequencing, struggle to fully clarify these changes because they generally fail to provide sufficient taxonomic resolution to adequately perform species-level associative studies. To improve CVM species designation, we designed a novel sequencing tool targeting microbes at the species taxonomic rank and examined its potential for profiling the CVM. RESULTS: We introduce an accessible and practical circular probe-based RNA sequencing (CiRNAseq) technology with the potential to profile and quantify the CVM. In vitro and in silico validations demonstrate that CiRNAseq can distinctively detect species in a mock mixed microbial environment, with the output data reflecting its ability to estimate microbes' abundance. Moreover, compared to 16S rRNA gene sequencing, CiRNAseq provides equivalent results but with improved sequencing sensitivity. Analyses of a cohort of cervical smears from hrHPV-negative women versus hrHPV-positive women with high-grade cervical intraepithelial neoplasia confirmed known differences in CST occurring in the CVM of women with hrHPV-induced lesions. The technique also revealed variations in microbial diversity and abundance in the CVM of hrHPV-positive women when compared to hrHPV-negative women. CONCLUSIONS: CiRNAseq is a promising tool for studying the interplay between the CVM and hrHPV in cervical carcinogenesis. This technology could provide a better understanding of cervicovaginal CST and microbial species during health and disease, prompting the discovery of biomarkers, additional to hrHPV, that can help detect high-grade cervical lesions

Organização do trabalho de enfermagem na Atenção Básica: uma questão para a saúde do trabalhador

Contains fulltext : 208073.pdf (publisher's version ) (Open Access

Maternal pre-pregnancy overweight and neonatal gut bacterial colonization are associated with cognitive development and gut microbiota composition in pre-school-age offspring

: Maternal gestational obesity is a risk factor for offspring's neurodevelopment and later neuro-cognitive disorders. Altered gut microbiota composition has been found in patients with neurocognitive disorders, and in relation to maternal metabolic health. We explored the associations between gut microbiota and cognitive development during infancy, and their link with maternal obesity. In groups of children from the Pisa birth Cohort (PISAC), we analysed faecal microbiota composition by 16S rRNA marker gene sequencing of first-pass meconium samples and of faecal samples collected at age 3, 6, 12, 24, 36 months, and its relationship with maternal gestational obesity or diabetes, and with cognitive development, as measured from 6 to 60 months of age by the Griffith's Mental Development Scales. Gut microbiota composition in the first phases of life is dominated by Bifidobacteria (Actinobacteria phylum), with contribution of Escherichia/Shigella and Klebsiella genera (Proteobacteria phylum), whereas Firmicutes become more dominant at 36 months of age. Maternal overweight leads to lower abundance of Bifidobacterium, Blautia and Ruminococcus, and lower practical reasoning scores in the offspring at the age of 36 months. In the whole population, microbiota in the first-pass meconium samples shows much higher alpha diversity compared to later samples, and its composition, particularly Bifidobacterium and Veillonella abundances, correlates with practical reasoning scores at 60 months of age. Maternal overweight correlates with bacterial colonization and with the development of reasoning skills at pre-school age. Associations between neonatal gut colonization and later cognitive function provide new perspectives of primary (antenatal) prevention of neurodevelopmental disorders

Reduce manual curation by combining gene predictions from multiple annotation engines, a case study of start codon prediction

Contains fulltext : 117193.pdf (publisher's version ) (Open Access)Nowadays, prokaryotic genomes are sequenced faster than the capacity to manually curate gene annotations. Automated genome annotation engines provide users a straight-forward and complete solution for predicting ORF coordinates and function. For many labs, the use of AGEs is therefore essential to decrease the time necessary for annotating a given prokaryotic genome. However, it is not uncommon for AGEs to provide different and sometimes conflicting predictions. Combining multiple AGEs might allow for more accurate predictions. Here we analyzed the ab initio open reading frame (ORF) calling performance of different AGEs based on curated genome annotations of eight strains from different bacterial species with GC% ranging from 35-52%. We present a case study which demonstrates a novel way of comparative genome annotation, using combinations of AGEs in a pre-defined order (or path) to predict ORF start codons. The order of AGE combinations is from high to low specificity, where the specificity is based on the eight genome annotations. For each AGE combination we are able to derive a so-called projected confidence value, which is the average specificity of ORF start codon prediction based on the eight genomes. The projected confidence enables estimating likeliness of a correct prediction for a particular ORF start codon by a particular AGE combination, pinpointing ORFs notoriously difficult to predict start codons. We correctly predict start codons for 90.5+/-4.8% of the genes in a genome (based on the eight genomes) with an accuracy of 81.1+/-7.6%. Our consensus-path methodology allows a marked improvement over majority voting (9.7+/-4.4%) and with an optimal path ORF start prediction sensitivity is gained while maintaining a high specificity

Correction: Supplementation of diet with non-digestible oligosaccharides alters the intestinal microbiota, but not arthritis development, in IL-1 receptor antagonist deficient mice.

[This corrects the article DOI: 10.1371/journal.pone.0219366.]

არჩილ გოგელია ახლობლებთან ერთად

მარცხნიდან: მესამე არჩილ გოგელია. გადაღების ადგილი და თარიაღი უცნობიაარჩილ გოგელია – გაზეთ „ ლელოს“ კორესპონდენტი (1962-1968) ტელევიზიისა და რადიო მაუწყებლობის სპორტულ გადაცემათა უფროსი, რედაქტორი გაზეთ „ლელოს“განყოფილების გამგე (1969-75) ჟურნალ „მართვეს“ დამაარსებელი დარედაქტორი. ჟურმალ „სკოლა და ცხოვრების“ მთავარი რედაქტორი გაზეთ „ლელოს“ მთავარი რედაქტორი გაზეთ „თბილისის“ მთავარი რედაქტორი(1985-1989) ტელერადიო მაუწყებლობის თავმჯდომარე( 1989-1991) საქარტველოს ჟურნალისტთა კავშირის მდივანი გაზეთ „დრონის“ დამაარსებელი და მთავარი რედაქტორი (1991- 1992) საქართველოს ინფორმაციის მინისტრი, ტელერადიო მაუწყებლობის პრეზიდენტი(1992- 1999) საქართველოს პარლამენტის წევრი (1999-2003) სეოკ-ის პრეზიდიუმის, ჟურნალისთა საერთაშორისო კავშირის წევრი, საქართველოს დამსახურებული ჟურნალისტი, 1000-ზე მეტიპუბლიცისტური წერილებისა და წიგნების : „მუშკეტერები“ და „ასეთია სპორტული ცხოვრება“ ავტორი. სპორტული მიღწევები: საქართველოს მრავალგზის ჩემპიონი სსრკ ხალხთა სპარტაკიადისა და ჩემპიონატების პრიზიორი საბჭოთა კავშირის თასის ფინალისტი საზოგადოება „სპარტაკის“ და სსრკ პროფკავშირების სპარტაკიადის ჩემპიონი სპორტის ოსტატი ფარიკაობაშ