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1.
Sci Adv ; 6(19): eaaz2433, 2020 05.
Article in English | MEDLINE | ID: mdl-32494709

ABSTRACT

Coxsackievirus B (CVB) enteroviruses are common human pathogens known to cause severe diseases including myocarditis, chronic dilated cardiomyopathy, and aseptic meningitis. CVBs are also hypothesized to be a causal factor in type 1 diabetes. Vaccines against CVBs are not currently available, and here we describe the generation and preclinical testing of a novel hexavalent vaccine targeting the six known CVB serotypes. We show that the vaccine has an excellent safety profile in murine models and nonhuman primates and that it induces strong neutralizing antibody responses to the six serotypes in both species without an adjuvant. We also demonstrate that the vaccine provides immunity against acute CVB infections in mice, including CVB infections known to cause virus-induced myocarditis. In addition, it blocks CVB-induced diabetes in a genetically permissive mouse model. Our preclinical proof-of-concept studies demonstrate the successful generation of a promising hexavalent CVB vaccine with high immunogenicity capable of preventing CVB-induced diseases.


Subject(s)
Coxsackievirus Infections , Myocarditis , Animals , Coxsackievirus Infections/prevention & control , Enterovirus B, Human , Mice , Primates , Vaccines, Combined
2.
Insect Mol Biol ; 25(6): 701-711, 2016 12.
Article in English | MEDLINE | ID: mdl-27438898

ABSTRACT

Most parthenogenetic weevil species are postulated to have originated via hybridization, but Wolbachia has also been speculated to play a role via the induction of parthenogenesis. Here, we examine the molecular diversity of Wolbachia and parthenogenetic host genomes. The host species studied here, Eusomus ovulum, is known to be exclusively parthenogenetic and triploid. The E. ovulum populations that we examined had a low genetic diversity of mitochondrial (cytochrome oxidase I gene) and nuclear markers (internal transcribed spacer 2 and elongation factor 1-α gene), and they all were infected by only single bacteria strains (genotyped for five genes according to the multilocus sequence typing system). We found significant signs of linkage disequilibrium and a lack of recombination amongst all of the examined genomes (bacteria and host), which strongly indicates a selective sweep. The lack of heterozygosity in host nuclear genes, missing bisexual populations and selective sweep between the parthenogenetic host and bacteria genomes suggest that parthenogenesis in this species could have originated as a result of infection rather than hybridization. However, the finding that highly similar Wolbachia strains are also present in other parthenogenetic weevils from the same habitat suggests the opposite scenario: bacteria may have infected the already parthenogenetic lineage and taken advantage of the host's unisexual reproduction.


Subject(s)
Genes, Bacterial , Genetic Variation , Genome, Insect , Insect Proteins/genetics , Linkage Disequilibrium , Weevils/genetics , Wolbachia/physiology , Animals , Cell Nucleus/genetics , Cell Nucleus/metabolism , DNA, Ribosomal Spacer/genetics , DNA, Ribosomal Spacer/metabolism , Electron Transport Complex IV/genetics , Electron Transport Complex IV/metabolism , Female , Insect Proteins/metabolism , Mitochondrial Proteins/genetics , Mitochondrial Proteins/metabolism , Multilocus Sequence Typing , Parthenogenesis , Peptide Elongation Factor 1/genetics , Peptide Elongation Factor 1/metabolism , Phylogeography , Sequence Analysis, DNA , Weevils/microbiology , Wolbachia/genetics
3.
Mol Ecol ; 24(15): 4023-38, 2015 Aug.
Article in English | MEDLINE | ID: mdl-26084200

ABSTRACT

DNA barcoding facilitates many evolutionary and ecological studies, including the examination of the dietary diversity of herbivores. In this study, we present a survey of ecological associations between herbivorous beetles and host plants from seriously threatened European steppic grasslands. We determined host plants for the majority (65%) of steppic leaf beetles (55 species) and weevils (59) known from central Europe using two barcodes (trnL and rbcL) and two sequencing strategies (Sanger for mono/oligophagous species and Illumina for polyphagous taxa). To better understand the ecological associations between steppic beetles and their host plants, we tested the hypothesis that leaf beetles and weevils differ in food selection as a result of their phylogenetic relations (within genera and between families) and interactions with host plants. We found 224 links between the beetles and the plants. Beetles belonging to seven genera feed on the same or related plants. Their preferences were probably inherited from common ancestors and/or resulted from the host plant's chemistry. Beetles from four genera feed on different plants, possibly reducing intrageneric competition and possibly due to an adaptation to different plant chemical defences. We found significant correlations between the numbers of leaf beetle and weevil species feeding on particular plants for polyphagous taxa, but not for nonpolyphagous beetles. Finally, we found that the previous identifications of host plants based on direct observations are generally concordant with host plant barcoding from insect gut. Our results expand basic knowledge about the trophic relations of steppic beetles and plants and are immediately useful for conservation purposes.


Subject(s)
Coleoptera/classification , Ecosystem , Herbivory , Plants/classification , Weevils/classification , Animals , DNA Barcoding, Taxonomic , Europe , Molecular Sequence Data , Phylogeny
4.
Article in Russian | MEDLINE | ID: mdl-7223216

ABSTRACT

The paper concerns results of the use of an information bank for purposes of optimizing, from the standpoint of a total systems approach, the structure and activity of psychiatric services in the region and enhancing the effectivity of the rehabilitative programmes. The main principles of forming the bank of information, including computer analogues of case histories, the system of managing the bases and models of optimizing the activities of facilities and their subunits, are described. A systemic coordination of such models provided a complete continuity in the activities of hospitals, dispensaries and intermediate subunits. This circumstance allowed an implementation of successful outpatient treatment in a large group of patients with a protracted development of diseases and consequently to enhance the efficacy of the activities of mental health services in the region.


Subject(s)
Information Systems , Mental Disorders/rehabilitation , Mental Health Services/organization & administration , Computers , Day Care, Medical/organization & administration , Hospitals, Psychiatric/organization & administration , Humans , Medical Records , Night Care/organization & administration , Rehabilitation, Vocational
5.
Article in Russian | MEDLINE | ID: mdl-7257686

ABSTRACT

The systems analysis approach to the work of a regional psychiatric service is described. Standard rehabilitation programs for principal groups of patients have been developed. These programs allow one to choose an optimal structure of the rehabilitation complex based on real requirements of the population. The complex includes a dispensary division, a hospital, a home treatment service, daytime and night wards, and workshops for occupational therapy. The disjunction of purposes and functions has provided complete succession in the work of all those services. The purposes and functions of each service are presented.


Subject(s)
Mental Disorders/rehabilitation , Mental Health Services/organization & administration , Systems Analysis , Ambulatory Care/organization & administration , Day Care, Medical/organization & administration , Home Care Services/organization & administration , Hospitalization , Humans , Night Care/organization & administration , Rehabilitation, Vocational , Social Adjustment , USSR
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