Pathogenetic Significance of Long Non-Coding RNAs in the Development of Thoracic and Abdominal Aortic Aneurysms.

Aortic aneurysm (AA) is a life-threatening condition with a high prevalence and risk of severe complications. The aim of this review was to summarize the data on the role of long non-coding RNAs (lncRNAs) in the development of AAs of various location. Within less than a decade of studies on the role of lncRNAs in AA, using experimental and bioinformatic approaches, scientists have obtained the data confirming the involvement of these molecules in metabolic pathways and pathogenetic mechanisms critical for the aneurysm development. Regardless of the location of pathological process (thoracic or abdominal aorta), AA was found to be associated with changes in the expression of various lncRNAs in the tissue of the affected vessels. The consistency of changes in the expression level of lncRNA, mRNA and microRNA in aortic tissues during AA development has been recordedand regulatory networks implicated in the AA pathogenesis in which lncRNAs act as competing endogenous RNAs (ceRNA networks) have been identified. It was found that the same lncRNA can be involved in different ceRNA networks and regulate different biochemical and cellular events; on the other hand, the same pathological process can be controlled by different lncRNAs. Despite some similarities in pathogenesis and overlapping of involved lncRNAs, the ceRNA networks described for abdominal and thoracic AA are different. Interactions between lncRNAs and other molecules, including those participating in epigenetic processes, have also been identified as potentially relevant to the AA pathogenesis. The expression levels of some lncRNAs were found to correlate with clinically significant aortic features and biochemical parameters. Identification of regulatory RNAs functionally significant in the aneurysm development is important for clarification of disease pathogenesis and will provide a basis for early diagnostics and development of new preventive and therapeutic drugs.

Application of Long-Read Nanopore Sequencing to the Search for Mutations in Hypertrophic Cardiomyopathy.

Increasing evidence suggests that both coding and non-coding regions of sarcomeric protein genes can contribute to hypertrophic cardiomyopathy (HCM). Here, we introduce an experimental workflow (tested on four patients) for complete sequencing of the most common HCM genes (MYBPC3, MYH7, TPM1, TNNT2, and TNNI3) via long-range PCR, Oxford Nanopore Technology (ONT) sequencing, and bioinformatic analysis. We applied Illumina and Sanger sequencing to validate the results, FastQC, Qualimap, and MultiQC for quality evaluations, MiniMap2 to align data, Clair3 to call and phase variants, and Annovar's tools and CADD to assess pathogenicity of variants. We could not amplify the region encompassing exons 6-12 of MYBPC3. A higher sequencing error rate was observed with ONT (6.86-6.92%) than with Illumina technology (1.14-1.35%), mostly for small indels. Pathogenic variant p.Gln1233Ter and benign polymorphism p.Arg326Gln in MYBPC3 in a heterozygous state were found in one patient. We demonstrated the ability of ONT to phase single-nucleotide variants, enabling direct haplotype determination for genes TNNT2 and TPM1. These findings highlight the importance of long-range PCR efficiency, as well as lower accuracy of variant calling by ONT than by Illumina technology; these differences should be clarified prior to clinical application of the ONT method.

Prevalence of the Microsporidian Nosema spp. in Honey Bee Populations (Apis mellifera) in Some Ecological Regions of North Asia.

Two species of microsporidia, Nosema apis and Nosema ceranae, are obligate intracellular parasites that are widespread in the world and cause the infectious disease (Nosemosis) of the Western honey bee Apis mellifera. Information on the prevalence and distribution of Nosema species in North Asia conditions is scarce. The main aim of the present study is to determine the prevalence of Nosema spp. (Nosemosis) in honey bees inhabiting some inland regions of North Asia (Western and Eastern Siberia, Altai Territory, Russia, and northeastern part of Kazakhstan). The objective of the paper is also to assess the influence of climatic factors on the spread of N. ceranae. Eighty apiaries in four ecological regions of North Asia (southern taiga, sub-taiga zone, forest steppe, and mountain taiga forests) were investigated with regard to distribution, prevalence, and diversity of Nosema infection in honey bees using duplex-PCR. Nosema infected bees were found in 65% apiaries of ecoregions studied, and coinfection was predominant (36.3% of Nosema-positive apiaries). Both N. apis and N. ceranae occur across subarctic and warm summer continental climates, but while N. apis predominates in the former, N. ceranae is more predominant in the latter. No statistically significant differences in Nosema distribution were identified in various climatic zones. In the sub-taiga zone (subarctic climate), low presence of colonies with pure N. ceranae and a significantly higher proportion of coinfection apiaries were revealed. Long-term epidemiological study of Nosema spp. prevalence in the sub-taiga zone showed a surprising percentage increase of Nosema-positive apiaries from 46.2% to 74.1% during 2012-2017. From 2012 to 2015, N. apis became a predominant species, but in 2016-2017, the coinfection was mainly detected. In conclusion, the results of this investigation showed that N. ceranae is widespread in all study ecoregions of North Asia where it exists in combination with the N. apis, but there is no replacement of N. apis by N. ceranae in the studied bee populations.

The Role of MicroRNA in Atherogenesis.

This review provides modern data on the spectrum and the functional significance of micro-RNAs involved in atherogenesis and on some regulatory mechanisms that ensure the functioning of this class of molecules. We also outline some examples of micro-RNAs use as diagnostic and therapeutic targets.