VASA-induced cytoplasmic localization of CYTB-positive mitochondrial substance occurs by destructive and nondestructive mitochondrial effusion, respectively, in early and late spermatogenic cells of the Manila clam

To analyze the release of mitochondrial material, a process that is believed to be (i) induced by the VASA protein derived from germplasm granules, and (ii) which appears to play an important role during meiotic differentiation, the localization of the CYTB protein was studied in the process of spermatogenesis of the bivalve mollusk Ruditapes philippinarum (Manila clam). It was found that in early spermatogenic cells, such as spermatogonia and spermatocytes, the CYTB protein shows dispersion in the cytoplasm following the total disaggregation of VASA-invaded mitochondria, what is called here as \u201cdestructive mitochondrial effusion (DME).\u201d It was found that the mitochondria of the maturing sperm cells also uptake VASA. It is accompanied by extramitochondrial transmembrane localization of CYTB assuming mitochondrial content release without mitochondrion demolishing. This phenomenon is called here as \u201cnondestructive mitochondrial effusion (NDME).\u201d Thus, in the spermatogenesis of the Manila clam, two patterns of mitochondrial release, DME and NDME, were found, which function, respectively, in early spermatogenic cells and in maturing spermatozoa. Despite the morphological difference, it is assumed that both DME and NDME have a similar functional nature. In both cases, the intramitochondrial localization of VASA coincides with the extramitochondrial localization of the mitochondrial matrix

Characterization of toxigenic Corynebacterium diphtheriae strains isolated in Russia

The aim of the study was to characterize toxigenic strains of Corynebacterium diphtheriae by examining 12 toxigenic strains of C. diphtheriae isolated in Russia between January, 2017 to June, 2019. The morphological, toxigenic and biochemical properties of C. diphtheriae was studied. Genotyping of C. diphtheriae strains was performed using MLST and dtxR gene sequencing with subsequent phylogenetic analysis. Results. Toxigenic strains of C. diphtheriae were isolated in the Novosibirsk, Samara and Chelyabinsk Regions, the Khanty-Mansi Autonomous Okrug — Yugra as well as the Republic of Northern Ossetia — Alania. Among these strains, 5 were isolated from diphtheria patients (moderate disease found in one case, mild course — remaining patients) and 7 strains were isolated from bacterial carriers. In two cases C. diphtheriae from diphtheria patients were identified as ST25 sequence type, gravis variant; in one case — ST8 type, gravis variant; two cases — ST67 sequence type, mitis variant. In asymptomatic carriers of tox-positive C. diphtheriae strains they belonged to ST25 sequence type, gravis variant — in two cases, ST67 type, mitis variant — in four cases. A sequencing type was not identified in one case. All sequence types were widespread globally being presented by a large number of isolates in the PubMLST and characterized by a substantial amount of derivative sequence types. At the same time, they belonged to different clonal complexes and differed markedly from each other contributing to their reliable difference as assessed by MLST. Study of gene dtxR sequence diversity showed that all allelic variants were typical for the representatives of these sequence types. New alleles of gene dtxR were not revealed in strains examined. It was shown that non-synonymous substitution C440T leading to A147V amino acid substitution was found solely in one allele distributed in ST8, ST185, ST195 and ST451 types suggesting at late mutation. In contrast, the polymorphism C640A resulting in the amino acid substitution L214I was found not only in the same allele, but also in the basal tree branches indicating that isoleucine was in the ancestral sequence of the protein

КЛИНИЧЕСКИЙ ОПЫТ ПРИМЕНЕНИЯ ВНУТРИПРОСВЕТНОЙ БРАХИТЕРАПИИ НА АППАРАТЕ «MULTISOURCE» У БОЛЬНЫХ РАКОМ ЛЕГКИХ И ТРАХЕИ

Treatment of primary and recurrent cancer of the trachea and main bronchi is a complex clinical problem. The article presents own experience of contact intraluminal radiation therapy in patients of this group. Efficacy and toxicity of this treatment was evaluated.Лечение первичного и рецидивного рака трахеи и главных бронхов является сложной клинической задачей. В статье представлен собственный опыт применения внутрипросветной контактной лучевой терапии улиц данной группы. Дана оценка эффективности и токсичности данного вида лечения

РЕЗУЛЬТАТЫ СОЧЕТАННОЙ ЛУЧЕВОЙ ТЕРАПИИ РАКА ПИЩЕВОДА С ПРИМЕНЕНИЕМ БРАХИТЕРАПИИ ВЫСОКОЙ МОЩНОСТИ

Between 2008 and 2015, 82 patients with inoperable esophageal cancer were treated with radiation therapy. The patients were divided into 3 groups. Group I consisted of 30 patients, who received external beam radiation therapy (EBRT) in combination with brachytherapy. Group II and group III patients (30 and 22 patients, respectively) received EBRT alone. Patients of group II received EBRT at a total dose of 60–70 Gy and patients of group III received EBRT at a total dose of 40–50 Gy. Treatment outcomes were better in patients treated with combination of EBRT and brachytherapy than in patients treated with EBRT alone. There was no significant difference between groups 2 and 3 with regard to their survival rates. Two-year overall survival rates in group I, II and III were 36 %, 12 % and 12 % and the median overall survival time was 15.7; 9.7 and 6.6 months, respectively.Проведено сравнительное исследование с включением 82 пациентов, страдающих раком пищевода, получивших самостоятельный курс лучевой терапии. В первую группу вошли 30 пациентов, получивших сочетанную лучевую терапию с брахитерапией, во 2-ю группу – 30 пациентов, получивших дистанционную лучевую терапию (ДЛТ) до суммарной дозы 60–70 Гр, у 22 пациентов 3-й группы суммарная доза ДЛТ была ограничена 40–50 Гр. Результаты лечения оказались лучше в группе сочетанной лучевой терапии, в то время как значение суммарной дозы ДЛТ не повлияло на показатели выживаемости. Двухлетняя общая выживаемость в сравниваемых группах составила 36, 12 и 12 %, медиана общей выживаемости – 15,7; 9,7 и 6,6 мес соответственно.

A common haplotype lowers PU.1 expression in myeloid cells and delays onset of Alzheimer's disease

A genome-wide survival analysis of 14,406 Alzheimer's disease (AD) cases and 25,849 controls identified eight previously reported AD risk loci and 14 novel loci associated with age at onset. Linkage disequilibrium score regression of 220 cell types implicated the regulation of myeloid gene expression in AD risk. The minor allele of rs1057233 (G), within the previously reported CELF1 AD risk locus, showed association with delayed AD onset and lower expression of SPI1 in monocytes and macrophages. SPI1 encodes PU.1, a transcription factor critical for myeloid cell development and function. AD heritability was enriched within the PU.1 cistrome, implicating a myeloid PU.1 target gene network in AD. Finally, experimentally altered PU.1 levels affected the expression of mouse orthologs of many AD risk genes and the phagocytic activity of mouse microglial cells. Our results suggest that lower SPI1 expression reduces AD risk by regulating myeloid gene expression and cell function

Blood-based biomarkers for Alzheimer disease: mapping the road to the clinic.

Biomarker discovery and development for clinical research, diagnostics and therapy monitoring in clinical trials have advanced rapidly in key areas of medicine - most notably, oncology and cardiovascular diseases - allowing rapid early detection and supporting the evolution of biomarker-guided, precision-medicine-based targeted therapies. In Alzheimer disease (AD), breakthroughs in biomarker identification and validation include cerebrospinal fluid and PET markers of amyloid-β and tau proteins, which are highly accurate in detecting the presence of AD-associated pathophysiological and neuropathological changes. However, the high cost, insufficient accessibility and/or invasiveness of these assays limit their use as viable first-line tools for detecting patterns of pathophysiology. Therefore, a multistage, tiered approach is needed, prioritizing development of an initial screen to exclude from these tests the high numbers of people with cognitive deficits who do not demonstrate evidence of underlying AD pathophysiology. This Review summarizes the efforts of an international working group that aimed to survey the current landscape of blood-based AD biomarkers and outlines operational steps for an effective academic-industry co-development pathway from identification and assay development to validation for clinical use.I recieved an honorarium from Roche Diagnostics for my participation in the advisory panel meeting leading to this pape

Influence of cure activator on the structure and properties of rubbers

The influence of vulcanization activator type on the properties of the compositions and elastic-strength characteristics of rubber was studied. Found that the modification of zinc oxide as the basis of actual formation curing vulcanization agents leads to an increase of vulcanization active centers, providing an increase in the velocity of rubber vulcanization and improvement of physical and mechanical rubber’s properties

In the Sea of Japan and the Adriatic Sea, a COX1 DNA test revealed genetic similarity of Manila clams, although shell parameters, spermatogenesis patterns, and sperm characteristics are area specific

The two Manila clam forms living in the Sea of Japan and in the Adriatic Sea were compared genetically and morphologically to identify traits that could be used to authenticate these geographic forms. COX1 DNA barcoding confirmed that both forms of these venerid bivalve belong to the species Ruditapes philippinarum (Adams and Reeve, 1850). It has also been shown that, based on COX1 analysis, it is not possible to separate these forms into different clusters based on geographic origin. However, some morphological features make it possible to differentiate these forms. It is noted that the contour of the shells of the Adriatic and Pacific molluscs is rounded and oblong, respectively. Underwater analysis of Pacific clams showed that shell color may be specific to specimens found at certain collection sites and differ between specimens taken from different collection sites. In the spermatogenesis of Adriatic and Pacific clams, a difference was found in the cellular mechanism of interaction between germplasm granules and mitochondria, manifested by distant contact and direct contact. Spermiogenesis has three similar lines of acrosome development, but differs in the number of ways in which the nucleus is formed. Due to the variability of the ways of sperm formation, heteromorphic morphs of spermatozoa are formed, the total number of which is six for the species R. philippinarum. In the Adriatic Manila clam, five morphs from this set are expressed. The Pacific Manila clam has only three sperm morphs. Only two sperm morphs are similar in both forms. In addition, each form is distinguished by the presence of unique sperm morphs and each form has its own type of dominant spermatozoon. Thus, the contour and color of the shells, as well as cytologic markers that have been found in the mechanisms of differentiation of meiotic cells and the characteristics of spermatozoa, can be used to distinguish the Adriatic and Pacific forms of the bivalve mollusc R. philippinarum