Excess amino acid polymorphism in mitochondrial DNA: contrasts among genes from Drosophila, mice, and humans

Recent studies of mitochondrial DNA (mtDNA) variation in mammals and Drosophila have shown an excess of amino acid variation within species (replacement polymorphism) relative to the number of silent and replacement differences fixed between species. To examine further this pattern of nonneutral mtDNA evolution, we present sequence data for the ND3 and ND5 genes from 59 lines of Drosophila melanogaster and 29 lines of D. simulans. Of interest are the frequency spectra of silent and replacement polymorphisms, and potential variation among genes and taxa in the departures from neutral expectations. The Drosophila ND3 and ND5 data show no significant excess of replacement polymorphism using the McDonald-Kreitman test. These data are in contrast to significant departures from neutrality for the ND3 gene in mammals and other genes in Drosophila mtDNA (cytochrome b and ATPase 6). Pooled across genes, however, both Drosophila and human mtDNA show very significant excesses of amino acid polymorphism. Silent polymorphisms at ND5 show a significantly higher variance in frequency than replacement polymorphisms, and the latter show a significant skew toward low frequencies (Tajima's D = -1.954). These patterns are interpreted in light of the nearly neutral theory where mildly deleterious amino acid haplotypes are observed as ephemeral variants within species but do not contribute to divergence. The patterns of polymorphism and divergence at charge-altering amino acid sites are presented for the Drosophila ND5 gene to examine the evolution of functionally distinct mutations. Excess charge-altering polymorphism is observed at the carboxyl terminal and excess charge-altering divergence is detected at the amino terminal. While the mildly deleterious model fits as a net effect in the evolution of nonrecombining mitochondrial genomes, these data suggest that opposing evolutionary pressures may act on different regions of mitochondrial genes and genomes.      

Associations of physical activity with gut microbiota in pre-adolescent children

[Purpose] To determine whether physical activity (PA), primarily the recommended 60 minutes of moderate-to-vigorous PA, is associated with gut bacterial microbiota in 10-year-old children.[Methods] The Block Physical Activity Screener, which provides minutes/day PA variables, was used to determine whether the child met the PA recommendations. 16S rRNA sequencing was performed on stool samples from the children to profile the composition of their gut bacterial microbiota. Differences in alpha diversity metrics (richness, Pielou’s evenness, and Faith’s phylogenetic diversity) by PA were determined using linear regression, whereas beta diversity (unweighted and weighted UniFrac) relationships were assessed using PERMANOVA. Taxon relative abundance differentials were determined using DESeq2.[Results] The analytic sample included 321 children with both PA and 16S rRNA sequencing data (mean age [SD] =10.2 [0.8] years; 54.2% male; 62.9% African American), where 189 (58.9%) met the PA recommendations. After adjusting for covariates, meeting the PA recommendations as well as minutes/day PA variables were not significantly associated with gut richness, evenness, or diversity (p ≥ 0.19). However, meeting the PA recommendations (weighted UniFrac R² = 0.014, p = 0.001) was significantly associated with distinct gut bacterial composition. These compositional differences were partly characterized by increased abundance of Megamonas and Anaerovorax as well as specific Christensenellaceae_R-7_group taxa in children with higher PA.[Conclusion] Children who met the recommendations of PA had altered gut microbiota compositions. Whether this translates to a reduced risk of obesity or associated metabolic diseases is still unclear.     

Association of polymorphisms in the human IL4 and IL5 genes with atopic bronchial asthma and severity of the disease

Two polymorphisms in the IL4 (G/C 3'-UTR) and IL5 (C-703T) genes were studied in a sample of families whose probands had atopic bronchial asthma (BA) (66 families, n = 183) and in a group of non-cognate individuals with the severe form of the disease (n = 34). The samples were collected from the Russian population in the city of Tomsk (Russia). Using the transmission/disequilibrium test (TDT), a significant association of allele C-703 IL5 with BA was established (TDT = 4.923, p = 0.007 +/- 0.0007). The analysis of 40 individuals with mild asthma and 49 patients with the severe form of the disease revealed a negative association of genotype GG IL4 (OR = 0.39, 95% CI = 0.15-0.99, p = 0.035), and also a trend towards a positive association of the GC IL4 genotype (OR = 2.52, 95% CI = 0.98-6.57, p = 0.052) with mild BA. There was a concordance of the clinical classification of BA severity with the 'genotype' (McNemar's chi(2) test with continuity correction constituted 0.03, d.f. = 1, p = 0.859). These results suggest that polymorphisms in the IL4 and IL5 genes contribute to the susceptibility to atopic BA and could determine the clinical course of the disease.     

Contractile properties of smooth muscles of bronchial tubes at formation of hyperreactance of airways

Contractile properties of smooth muscles of bronchial tubes of porpoises in formation of hyperreactance airways, were studied. Sensitization by ovalbumin results in formation of hyperresponsiveness of the airways as shown in increase in amplitude of contractile responses to histaminergic influences and oppression of adrenergic relaxations of segments. Respiratory epithelium oppresses contractile responses of airways in intact animals to histaminergic influences. Influence of epithelium on adrenergic responses depends on precontractile factor: they increase in prereduction by histamine. In formation of hyperresponse, the epithelium loses ability to modulate responses of smooth muscles of the airways. Incubation segments of smooth muscles of the airways in interleukin 5 increases contractile responses to histaminergic influences. Receptor of interleukin 5 (the soluble fraction) neutralizes the effect of exogenous interleukin 5, and incubation of receptor of sensitized animals oppresses histaminergic contractile responses.     

Opisthorchis felineus and Metorchis bilis are the main agents of liver fluke infection of humans in Russia

Liver fluke infections are gradually transforming from a local problem of individual geographic regions to a widespread problem. The observed expansion is likely to be connected with the ever-increasing intensity of traffic flow and migration of the infected carriers between cities, regions, and countries. Opisthorchis felineus, the trematode belonging to the family Opisthorchiidae, is a well known causative agent of the infection called opisthorchiasis. Metorchis bilis, also a member of the family Opisthorchiidae, causes metorchiasis, a disease very close to opisthorchiasis in symptomatology. Genetic markers can be used to develop methods for differential diagnostics of these diseases. However, the questions connected with epidemiology of these trematode infections, their clinical characteristics, prognosis and therapy remain open. This review briefs the general biological characteristics of O. felineus and M. bilis persisting in various countries of Eurasia, their geographical range, epidemiology and molecular diagnostics of these liver flukes.     

A radioimmunoprecipitation method in the serodiagnosis of HIV infection: the development of the optimal conditions for its performance and the evaluation of the possibilities for its use

The optimum conditions for using the method of radioimmunoprecipitation (RIP) for the detection of human immunodeficiency virus (HIV) in serum samples have been established. Out of several available cell lines persistently infected with HIV, specially selected line 17 has been chosen. The characteristic feature of this is the high and stable (under the conditions of prolonged cultivation) accumulation of virus-specific proteins in infected cells. The optimum conditions for making the test and its evaluation have also been established. The data of literature on the advantages of the method of RIP over such traditional methods as the enzyme immunoassay and immunoblotting have been confirmed. Thus, the presence of specific antibodies in several serum samples registered as false negative has been established. The intertypical reactivity of two serotypes of the virus, HIV-1 and HIV-2, has been studied. Cross reactivity of antibodies with respect to the HIV gene gag, but not with respect to viral glycoproteids, has been established. Ideas on the expediency and prospects of using RIP for the serological control of HIV infection are presented.     

Recruitment of TBK1 to cytosol‐invading Salmonella induces WIPI2‐dependent antibacterial autophagy

Mammalian cells deploy autophagy to defend their cytosol against bacterial invaders. Anti‐bacterial autophagy relies on the core autophagy machinery, cargo receptors, and “eat‐me” signals such as galectin‐8 and ubiquitin that label bacteria as autophagy cargo. Anti‐bacterial autophagy also requires the kinase TBK1, whose role in autophagy has remained enigmatic. Here we show that recruitment of WIPI2, itself essential for anti‐bacterial autophagy, is dependent on the localization of catalytically active TBK1 to the vicinity of cytosolic bacteria. Experimental manipulation of TBK1 recruitment revealed that engagement of TBK1 with any of a variety of Salmonella‐associated “eat‐me” signals, including host‐derived glycans and K48‐ and K63‐linked ubiquitin chains, suffices to restrict bacterial proliferation. Promiscuity in recruiting TBK1 via independent signals may buffer TBK1 functionality from potential bacterial antagonism and thus be of evolutionary advantage to the host.