FUNCTIONAL POLYMORPHISM OF THE PRO-INFLAMMATORY CYTOKINE GENES IN PULMONARY TUBERCULOSIS

In the present time, incidence of pulmonary tuberculosis (TB) becomes broader, due to spreading resistance of Mycobacterium tuberculosis (MBT) to anti-tuberculosis drugs and infection with highly virulent strains of M. tuberculosis. The MBT antigens can cause dysfunction of the receptors and modulate the cytokine secreting function of immunocompetent cells. Polymorphic genes of pro-inflammatory cytokines involved in the mechanisms of defense responses of innate immunity, determine the degree of resistance to individual mycobacterial infection, as well as severity and duration of the disease in cases of clinical manifestations. The aim of the study was to investigate the connections between allelic polymorphisms of IL2, IFNG and TNFA genes and changes in secretion of the corresponding pro-inflammatory cytokines IL-2, IFNγ, and TNFα in vitro in patients with the newly diagnosed pulmonary tuberculosis (TB), depending on the clinical form of the disease.A total of 334 patients (220 men and 114 women) aged 23 to 50 years with newly diagnosed infiltrative and disseminated TB were enrolled into the study. The control group consisted of 183 healthy donors (130 men and 53 women) of corresponding age. The material of the research included DNA extracted from the whole blood and supernatants of culture suspensions of mononuclear leukocytes isolated from venous blood in healthy volunteers and patients with TB. The evaluation of cytokines secretion was performed by measuring their concentration in the blood mononuclear cell culture supernatants. using enzyme-linked immunosorbent assay (ELISA). To study polymorphic regions of cytokine genes, a polymerase chain reaction (PCR) was applied. Analysis of the obtained data was carried out by means of the program Statistica for Windows Version 6.0 (StatSoft Inc., USA).It was found that the imbalance of secretion of pro-inflammatory cytokines in TB patients was associated with the polymorphic variants of genes of these cytokines. It was found that the hypo-secretion of IL-2 is determined by the carriage of the G allele and genotype GG (T-330G) of the IL2 gene in both the control group and in patients with TB, regardless of the clinical form. In patients with DTB carriers of the homozygous genotype TT (T-330G) of the IL2gene, increased protein secretion was established. The maximum secretion of TNFб was recorded in patients with the AA genotype (G-308A) of the TNFA gene in the control group and in ITB patients; the minimum concentration of TNFα was associated with the carrier of the homozygous GG genotype (G-308A) of the TNFA gene in all the examined groups. In patients with ITB and DTB, an increase in IFNγ secretion by mononuclear blood leukocytes is not associated with the carrier of polymorphism +874A/T of the IFNG gene.Reduced secretion of IL-2 and TNFα in TB patients is associated with polymorphisms of their genes – (T-330G) of IL2 gene and (G-308A) of TNFA gene, respectively. The polymorphism (+874A/T) of the IFNG gene does not have a modulatory effect on the secretion of IFNγ in patients with TB, regardless of clinical form of the disease

Evolution of Sex-Specific Traits through Changes in HOX-Dependent doublesex Expression

Analysis in Drosophila suggests that evolutionary changes in the spatial regulation of the transcription factor doublesex play a key role in the origin, diversification, and loss of sex-specific structures

Resolved photometry of extragalactic young massive star clusters

We present colour-magnitude diagrams (CMDs) for a sample of seven young massive clusters in the galaxies NGC 1313, NGC 1569, NGC 1705, NGC 5236 and NGC 7793. The clusters have ages in the range 5-50 million years and masses of 10^5 -10^6 Msun. Although crowding prevents us from obtaining photometry in the central regions of the clusters, we are still able to measure up to 30-100 supergiant stars in each of the richest clusters, along with the brighter main sequence stars. The resulting CMDs and luminosity functions are compared with photometry of artificially generated clusters, designed to reproduce the photometric errors and completeness as realistically as possible. In agreement with previous studies, our CMDs show no clear gap between the H-burning main sequence and the He-burning supergiant stars, contrary to predictions by common stellar isochrones. In general, the isochrones also fail to match the observed number ratios of red-to-blue supergiant stars, although the difficulty of separating blue supergiants from the main sequence complicates this comparison. In several cases we observe a large spread (1-2 mag) in the luminosities of the supergiant stars that cannot be accounted for by observational errors. This spread can be reproduced by including an age spread of 10-30 million years in the models. However, age spreads cannot fully account for the observed morphology of the CMDs and other processes, such as the evolution of interacting binary stars, may also play a role.Comment: 15 pages, 12 figures, accepted for publication in A&

Highly Contiguous Assemblies of 101 Drosophilid Genomes

Over 100 years of studies in Drosophila melanogaster and related species in the genus Drosophila have facilitated key discoveries in genetics, genomics, and evolution. While high-quality genome assemblies exist for several species in this group, they only encompass a small fraction of the genus. Recent advances in long-read sequencing allow high-quality genome assemblies for tens or even hundreds of species to be efficiently generated. Here, we utilize Oxford Nanopore sequencing to build an open community resource of genome assemblies for 101 lines of 93 drosophilid species encompassing 14 species groups and 35 sub-groups. The genomes are highly contiguous and complete, with an average contig N50 of 10.5 Mb and greater than 97% BUSCO completeness in 97/101 assemblies. We show that Nanopore-based assemblies are highly accurate in coding regions, particularly with respect to coding insertions and deletions. These assemblies, along with a detailed laboratory protocol and assembly pipelines, are released as a public resource and will serve as a starting point for addressing broad questions of genetics, ecology, and evolution at the scale of hundreds of species

Опыт применения препарата бедаквилин у ребенка раннего возраста с лекарственно-устойчивым туберкулезом на фоне первичного иммунодефицита

The article describes a clinical case of the treatment of a young child with a complicated course of tuberculosis with multiple localizations and concurrent primary immunodeficiency. The new anti-tuberculosis drug of bedaquiline was successfully used in the treatment regimen. The child received bedaquiline for 6 months without any adverse events, after 2 months no acid-fast mycobacteria were detected, there were pronounced positive radiological changes which remained until the end of treatment. This clinical case provides evidence that bedaquiline can be used safely and effectively in MDR TB chemotherapy regimens in children under 5 years of age.Представлено клиническое наблюдение лечения ребенка раннего возраста с осложненным течением туберкулеза множественных локализаций на фоне первичного иммунодефицита. В схеме лечения успешно использован новый противотуберкулезный препарат бедаквилин. Ребенок получал бедаквилин в течение 6 мес. без нежелательных явлений, через 2 мес. прекратилось выделение кислотоустойчивых микобактерий, отмечалась выраженная положительная рентгенологическая динамика, сохранявшаяся до конца лечения. Клиническое наблюдение свидетельствует, что бедаквилин может быть безопасно и эффективно использован в схеме химиотерапии МЛУ-туберкулеза у детей младше 5 лет