Inhibitory Activity of - and -Functionalized Monoterpene Diols Towards Monoamine Oxidases A and B.

Monoamine oxidase B (MAO-B) inhibitors are widely used as part of combination drug therapy for Parkinson's disease. As demonstrated in both in vitro and in vivo experiments, the monoterpenoid Prottremine and some of its derivatives exhibit high antiparkinsonian activity. In this study, the inhibitory activity of Prottremine and its derivatives (including 14 new 9-- and -derivatives) against MAO-A and MAO-B enzymes has been investigated for the first time.

Blood Lipid Polygenic Risk Score Development and Application for Atherosclerosis Ultrasound Parameters.

The present study investigates the feasibility of using three previously published genome-wide association studies (GWAS) results on blood lipids to develop polygenic risk scores (PRS) for population samples from the European part of the Russian Federation. Two population samples were used in the study - one from the Ivanovo region ( = 1673) and one from the Vologda region ( = 817). We investigated three distinct approaches to PRS development: using the straightforward PRS approach with original effect sizes and fine-tuning with PRSice-2 and LDpred2.

Generation and characterization of two induced pluripotent stem cell lines (ICGi052-A and ICGi052-B) from a patient with frontotemporal dementia with parkinsonism-17 associated with the pathological variant c.2013T>G in the MAPT gene.

Frontotemporal dementia with parkinsonism-17 is a neurodegenerative disease characterised by pathological aggregation of the tau protein with the formation of neurofibrillary tangles and subsequent neuronal death. The inherited form of frontotemporal dementia can be caused by mutations in several genes, including the MAPT gene on chromosome 17, which encodes the tau protein. As there are currently no medically approved treatments for frontotemporal dementia, there is an urgent need for research using in vitro cell models to understand the molecular genetic mechanisms that lead to the development of the disease, to identify targets for therapeutic intervention and to test potential drugs to prevent neuronal death.

Clinical and biochemical features of atherogenic hyperlipidemias with different genetic basis: A comprehensive comparative study.

Patients with genetically-based hyperlipidemias exhibit a wide phenotypic variability. Investigation of clinical and biochemical features is important for identifying genetically-based hyperlipidemias, determining disease prognosis, and initiating timely treatment. We analyzed genetic data from 3374 samples and compared clinical data, lipid levels (low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, triglycerides, and lipoprotein (a)), frequency, age at onset of coronary heart disease (CHD), and the severity of carotid and femoral atherosclerosis (plaque number, maximum stenosis, total stenosis, maximum plaque height, and plaque score) among patients with familial hypercholesterolemia (FH), familial dysbetalipoproteinemia (FD), polygenic hypercholesterolemia (HCL), severe HCL, and those without lipid disorders (n = 324).

Spectrum and Prevalence of Rare Variants and Their Association with Familial Dysbetalipoproteinemia.

Familial dysbetalipoproteinemia (FD) is a highly atherogenic, prevalent genetically based lipid disorder. About 10% of FD patients have rare variants associated with autosomal dominant FD. However, there are insufficient data on the relationship between rare variants and FD.

A Rare Coincidence of Three Inherited Diseases in a Family with Cardiomyopathy and Multiple Extracardiac Abnormalities.

A genetic diagnosis of primary cardiomyopathies can be a long-unmet need in patients with complex phenotypes. We investigated a three-generation family with cardiomyopathy and various extracardiac abnormalities that had long sought a precise diagnosis. The 41-year-old proband had hypertrophic cardiomyopathy (HCM), left ventricular noncompaction, myocardial fibrosis, arrhythmias, and a short stature.

Applicability of Diagnostic Criteria and High Prevalence of Familial Dysbetalipoproteinemia in Russia: A Pilot Study.

Familial dysbetalipoproteinemia (FD) is a highly atherogenic genetically based lipid disorder with an underestimated actual prevalence. In recent years, several biochemical algorithms have been developed to diagnose FD using available laboratory tests. The practical applicability of FD diagnostic criteria and the prevalence of FD in Russia have not been previously assessed.

Learning the native pond odor as one of the mechanisms of olfactory orientation in juvenile smooth newt Lissotriton vulgaris.

Olfaction is an important mechanism of orientation in amphibians toward the breeding site. It is known that anurans can memorize the odor of the native pond during larval development and prefer this odor prior to the beginning of dispersion. However, such a mechanism in urodeles has not been studied yet.

The Metagenomic Analysis of Viral Diversity in Colorado Potato Beetle Public NGS Data.

The Colorado potato beetle (CPB) is one of the most serious insect pests due to its high ecological plasticity and ability to rapidly develop resistance to insecticides. The use of biological insecticides based on viruses is a promising approach to control insect pests, but the information on viruses which infect leaf feeding beetles is scarce. We performed a metagenomic analysis of 297 CPB genomic and transcriptomic samples from the public National Center for Biotechnology Information Sequence Read Archive (NCBI SRA) database.

A Case of Severe Left-Ventricular Noncompaction Associated with Splicing Altering Variant in the Gene.

Left ventricular noncompaction (LVNC) is a highly heterogeneous primary disorder of the myocardium. Its clinical features and genetic spectrum strongly overlap with other types of primary cardiomyopathies, in particular, hypertrophic cardiomyopathy. Study and the accumulation of genotype-phenotype correlations are the way to improve the precision of our diagnostics.

Generation of induced pluripotent stem cell line, ICGi034-A, by reprogramming peripheral blood mononuclear cells from a patient with Parkinson's disease associated with GBA mutation.

Mutation in the glucocerebrosidase encoding gene (GBA) is one of the most frequent genetic cause of Parkinson's disease. ICGi034-A induced pluripotent stem cell (iPSC) line obtained by reprogramming peripheral blood mononuclear cells (PBMCs) of a patient with heterozygous c.1226A > G (p.

Targeted Sequencing of 242 Clinically Important Genes in the Russian Population From the Ivanovo Region.

We performed a targeted sequencing of 242 clinically important genes mostly associated with cardiovascular diseases in a representative population sample of 1,658 individuals from the Ivanovo region northeast of Moscow. Approximately 11% of 11,876 detected variants were not found in the Single Nucleotide Polymorphism Database (dbSNP) or reported earlier in the Russian population. Most novel variants were singletons and doubletons in our sample, and virtually no novel alleles presumably specific for the Russian population were able to reach the frequencies above 0.

Very long intergenic non-coding (vlinc) RNAs directly regulate multiple genes in cis and trans.

Background: The majority of the human genome is transcribed in the form of long non-coding (lnc) RNAs. While these transcripts have attracted considerable interest, their molecular mechanisms of function and biological significance remain controversial. One of the main reasons behind this lies in the significant challenges posed by lncRNAs requiring the development of novel methods and concepts to unravel their functionality.

Generation of an induced pluripotent stem cell line, ICGi028-A, by reprogramming peripheral blood mononuclear cells of a patient suffering from hypertrophic cardiomyopathy and carrying a heterozygous p.E510Q mutation in HADHA.

Hypertrophic cardiomyopathy (HCM) is a frequent cardiovascular pathology caused by a huge number of mutations in sarcomere-associated proteins. This genetic diversity leads to differences in pathogenetic mechanisms and hampers HCM therapy. Cardiomyocytes derived from patient-specific induced pluripotent stem cells give new opportunities for studying underlying HCM mechanisms.

Study of the effect of the introduction of mitochondrial import determinants into the gRNA structure on the activity of the gRNA/SpCas9 complex in vitro.

It has long been known that defects in the structure of the mitochondrial genome can cause various neuromuscular and neurodegenerative diseases. Nevertheless, at present there is no effective method for treating mitochondrial diseases. The major problem with the treatment of such diseases is associated with mitochondrial DNA (mtDNA) heteroplasmy.

Style transfer with variational autoencoders is a promising approach to RNA-Seq data harmonization and analysis.

Motivation: The transcriptomic data are being frequently used in the research of biomarker genes of different diseases and biological states. The most common tasks there are the data harmonization and treatment outcome prediction. Both of them can be addressed via the style transfer approach.

Generation of induced pluripotent stem cell lines ICGi021-A and ICGi022-A from peripheral blood mononuclear cells of two healthy individuals from Siberian population.

ICGi021-A and ICGi022-A iPSC lines were obtained by reprogramming PBMCs of two healthy women of the Siberian population using episomal non-integrating vectors expressing Yamanaka factors. iPSC lines expressed pluripotency markers, had a normal karyotype and demonstrated the ability to differentiate into derivatives of the three germ layers. Clinical exome sequencing data of the original biosamples of the donors are available in the NCBI SRA database.

Generation of three Duchenne muscular dystrophy patient-derived induced pluripotent stem cell (iPSC) lines ICGi002-A, ICGi002-B and ICGi002-C.

Duchenne muscular dystrophy (DMD) is a severe and rapidly progressive hereditary muscular disease with X-linked recessive inheritance, occurring mainly in males. A complete loss of dystrophin resulted from out-of-frame deletion mutations in the DMD gene leads to Duchenne muscular dystrophy. DMD induced pluripotent stem cells (iPSCs) are a suitable cell model to study muscle development and disease mechanisms underlying muscular dystrophy and to screen novel compounds with potential therapeutic effects.

Generation of two clonal iPSC lines, ICGi019-A and ICGi019-B, by reprogramming peripheral blood mononuclear cells of a patient suffering from hypertrophic cardiomyopathy and carrying a heterozygous p.M659I mutation in MYH7.

Hypertrophic cardiomyopathy (HCM) is one of the most frequent cardiovascular diseases but no methods to prevent its progression have been developed. Cardiomyocytes derived from patient-specific induced pluripotent stem cells can become a platform to study pathogenesis of the disease and to search for more effective therapy methods. We generated two iPSC lines from peripheral blood mononuclear cells of an HCM patient with heterozygous p.

Generation of two iPSC lines, (ICGi015-A and ICGi015-B), by reprogramming peripheral blood mononuclear cells from a patient with Parkinson's disease.

Studying Parkinson's disease (PD), one of the most common neurodegenerative disorders worldwide, requires different model systems, including patient-specific induced pluripotent stem cell lines. With the help of non-integrating episomal vectors the iPSC lines ICGi015-A and ICGi015-B were generated from blood mononuclear cells of PD patient, carrying three SNPs, associated with PD development. The obtained iPSC lines express pluripotency markers and demonstrate the ability to in vitro differentiate into the three germ layers.

A New MicroRNA Cluster Involved in the Reprogramming to a Pluripotent State.

Reprogramming of somatic cells to a pluripotent state is a complex, multistage process that is regulated by many factors. Among these factors, non-coding RNAs and microRNAs (miRNAs) have been intensively studied in recent years. MiRNAs play an important role in many processes, particularly in cell reprogramming.