G-quadruplexes in an SVA retrotransposon cause aberrant TAF1 gene expression in X-linked dystonia parkinsonism.

G-quadruplexes (G4s) are non-canonical nucleic acid structures that form in guanine (G)-rich genomic regions. X-linked dystonia parkinsonism (XDP) is an inherited neurodegenerative disease in which a SINE-VNTR-Alu (SVA) retrotransposon, characterised by amplification of a G-rich repeat, is inserted into the coding sequence of TAF1, a key partner of RNA polymerase II. XDP SVA alters TAF1 expression, but the cause of this outcome in XDP remains unknown.

The histone H4K20 methyltransferase SUV4-20H1/KMT5B is required for multiciliated cell differentiation in Xenopus.

H4 lysine 20 dimethylation (H4K20me2) is the most abundant histone modification in vertebrate chromatin. It arises from sequential methylation of unmodified histone H4 proteins by the mono-methylating enzyme PR-SET7/KMT5A, followed by conversion to the dimethylated state by SUV4-20H (KMT5B/C) enzymes. We have blocked the deposition of this mark by depleting Xenopus embryos of SUV4-20H1/H2 methyltransferases.

HIV-1 infection activates endogenous retroviral promoters regulating antiviral gene expression.

Although endogenous retroviruses (ERVs) are known to harbor cis-regulatory elements, their role in modulating cellular immune responses remains poorly understood. Using an RNA-seq approach, we show that several members of the ERV9 lineage, particularly LTR12C elements, are activated upon HIV-1 infection of primary CD4+ T cells. Intriguingly, HIV-1-induced ERVs harboring transcription start sites are primarily found in the vicinity of immunity genes.

Sensorimotor and sensory gating in depression, anxiety, and their comorbidity.

Objectives: Abnormal attentional and cognitive processes are thought to increase the risk for depression and anxiety. To improve understanding of brain mechanisms of anxiety and depressive disorders and condition of their comorbidity, the study of early attentional processes was provided.

Methods: Participants were patients with depressive (80 s.

Systematic dissection of biases in whole-exome and whole-genome sequencing reveals major determinants of coding sequence coverage.

Advantages and diagnostic effectiveness of the two most widely used resequencing approaches, whole exome (WES) and whole genome (WGS) sequencing, are often debated. WES dominated large-scale resequencing projects because of lower cost and easier data storage and processing. Rapid development of 3 generation sequencing methods and novel exome sequencing kits predicate the need for a robust statistical framework allowing informative and easy performance comparison of the emerging methods.

Analytical "bake-off" of whole genome sequencing quality for the Genome Russia project using a small cohort for autoimmune hepatitis.

A comparative analysis of whole genome sequencing (WGS) and genotype calling was initiated for ten human genome samples sequenced by St. Petersburg State University Peterhof Sequencing Center and by three commercial sequencing centers outside of Russia. The sequence quality, efficiency of DNA variant and genotype calling were compared with each other and with DNA microarrays for each of ten study subjects.

Transcriptome of the bivalve Limecola balthica L. from Western Pacific: A new resource for studies of European populations.

The Baltic clam Limecola balthica L. (Tellinidae) is broadly used in ecophysiological, toxicological, evolutionary and environmental monitoring studies. However, it is poorly studied in respect of genome and gene functions.

Alternative spliceosome assembly pathways revealed by single-molecule fluorescence microscopy.

Removal of introns from nascent transcripts (pre-mRNAs) by the spliceosome is an essential step in eukaryotic gene expression. Previous studies have suggested that the earliest steps in spliceosome assembly in yeast are highly ordered and the stable recruitment of U1 small nuclear ribonucleoprotein particle (snRNP) to the 5' splice site necessarily precedes recruitment of U2 snRNP to the branch site to form the "prespliceosome." Here, using colocalization single-molecule spectroscopy to follow initial spliceosome assembly on eight different S.

β-carboline compounds, including harmine, inhibit DYRK1A and tau phosphorylation at multiple Alzheimer's disease-related sites.

Harmine, a β-carboline alkaloid, is a high affinity inhibitor of the dual specificity tyrosine phosphorylation regulated kinase 1A (DYRK1A) protein. The DYRK1A gene is located within the Down Syndrome Critical Region (DSCR) on chromosome 21. We and others have implicated DYRK1A in the phosphorylation of tau protein on multiple sites associated with tau pathology in Down Syndrome and in Alzheimer's disease (AD).

Potential bridges of heterosexual HIV transmission from drug users to the general population in St. Petersburg, Russia: is it easy to be a young female?

The epidemic of HIV in St. Petersburg, which is currently concentrated among injection drug users (IDUs), may be penetrating into the general population. Non-IDUs who have IDU sex partners (SP) could be potential bridges in an expanding epidemic.

The potential for bridging of HIV transmission in the Russian Federation: sex risk behaviors and HIV prevalence among drug users (DUs) and their non-DU sex partners.

The HIV epidemic that began in Russia in the mid-1990s has been concentrated mostly among drug users (DUs). Recent evidence of increasing HIV cases among non-DUs attributed to sexual behavior raises potential concern about a more generalized epidemic. The purpose of this analysis is to examine the potential for HIV transmission from DUs to their non-DU sex partners.

[MRI-parameters of frontal lobes in schizophrenia: correlations with the level of autoantibodies to nerve growth factor in the blood serum].

The relationship between MRI-parameters of frontal lobes and levels of autoantibodies to nerve growth factor (Aab-NGF) in the blood serum of patients with schizophrenia and their relatives was studied. The negative correlation between the Aab-NGF level and the total volume of frontal lobes (r= -0,59; p<0,01) was found in the group of patients. No significant correlations were found in the control groups of healthy subjects without family history of schizophrenia and relatives of patients.

Rapid quantification and analysis of kinetic •OH radical footprinting data using SAFA.

The use of highly reactive chemical species to probe the structure and dynamics of nucleic acids is greatly simplified by software that enables rapid quantification of the gel images that result from these experiments. Semiautomated footprinting analysis (SAFA) allows a user to quickly and reproducibly quantify a chemical footprinting gel image through a series of steps that rectify, assign, and integrate the relative band intensities. The output of this procedure is raw band intensities that report on the relative reactivity of each nucleotide with the chemical probe.

Hydroxyl-radical footprinting to probe equilibrium changes in RNA tertiary structure.

Hydroxyl-radical footprinting utilizes the ability of a highly reactive species to nonspecifically cleave the solvent accessible regions of a nucleic acid backbone. Thus, changes in a nucleic acids structure can be probed either as a function of time or of a reagent's concentration. When combined with techniques that allow single nucleotide resolution of the resulting fragments, footprinting experiments provide richly detailed information about local changes in tertiary structure of a nucleic acid accompanying its folding or ligand binding.

[Molecular-genetic and epidemiologic examination of personnel subjected to occupational irradiation in Russian Federal Nuclear Center (Sarov). Report 3. Genetic characteristics of adaptive norm].

Was undertaken the effort to define the limits of the adaptive norms and of high risk groups in regard to the work connected with fissile materials (FM), radioactive materials (RM) and ionizing radiation sources (IRS). In view of the aforementioned goal it was made a comparative evaluation of the individual radiosensitivity measurements and anthropometric indicators in the cohort formed from VNIIEF personnel, which was exposed to a constant occupational gamma-neutron irradiation, as well as the non-irradiated cohort. There were analyzed the dispersion dependencies on height, on chest and on head circumference and heterozygosis by 9 loci.

[Molecular-genetic and epidemiologic examination of personnel subjected to occupational irradiation in the Russian Federal Nuclear Center (Sarov). Report 2. Genetic and non-genetic risk factors of morbidity].

Below is given a comparative evaluation of the genetic and the epidemiological examination of the cohort comprised by VNIIEF personnel subjected chronically to gamma-neutron ionizing radiation (74 persons), as well as nonirradiated cohort (74 persons). There are obtained data on the influence of the integral genotype structure on the health of an individual in case of occupational irradiation. The epidemiological analysis revealed statistically meaningful differences between the main and the control cohorts in the following five cases: acute respiratory diseases, diseases of upper respiratory tract, brain vessel malfunctions; illnesses connected with vision organs and cardio-vascular system and traumas.

[Molecular-genetic and epidemiologic examination of personnel subjected to occupational irradiation in Russian Federal Nuclear Center (Sarov). Report 1. Genome structural damage rate and radiosensitivity].

A comparative evaluation of the cytological and dosimetric examination of the cohort comprised by VNIEF personnel subjected chronically to gamma-neutron ionizing radiation, as well as non-irradiated cohort is given. The obtained data on the influence of the occupational and on X-ray irradiation, age and smoking on the rate of structural genome damage, as well as the activity of the human repair system activity are presented. The influence of the individual heterozygosis by 9 polymorphous loci: Hp, Tf, Gc; 6-PGD, EsD, ACP, PGM1, microsatellite lici SCF1PO and F13AO1 is shown.

Energy barriers, pathways, and dynamics during folding of large, multidomain RNAs.

Large, multidomain RNA molecules are generally thought to fold following multiple pathways down rugged landscapes populated with intermediates and traps. A challenge to understanding RNA folding reactions is the complex relationships that exist between the structure of the RNA and its folding landscape. The identification of intermediate species that populate folding landscapes and characterization of elements of their structures are the key components to solving the RNA folding problem.

Function and structural organization of Mot1 bound to a natural target promoter.

Mot1 is an essential, conserved TATA-binding protein (TBP)-associated factor in Saccharomyces cerevisiae and a member of the Snf2/Swi2 ATPase family. Mot1 uses ATP hydrolysis to displace TBP from DNA, an activity that can be readily reconciled with its global role in gene repression. Less well understood is how Mot1 directly activates gene expression.

High-throughput single-nucleotide structural mapping by capillary automated footprinting analysis.

The use of capillary electrophoresis with fluorescently labeled nucleic acids revolutionized DNA sequencing, effectively fueling the genomic revolution. We present an application of this technology for the high-throughput structural analysis of nucleic acids by chemical and enzymatic mapping ('footprinting'). We achieve the throughput and data quality necessary for genomic-scale structural analysis by combining fluorophore labeling of nucleic acids with novel quantitation algorithms.

Monitoring structural changes in nucleic acids with single residue spatial and millisecond time resolution by quantitative hydroxyl radical footprinting.

Hydroxyl radical (.OH) footprinting provides comprehensive site-specific quantitative information about the structural changes associated with macromolecular folding, interactions and ligand binding. 'Fast Fenton' footprinting is a laboratory-based method for time-resolved .

Following molecular transitions with single residue spatial and millisecond time resolution.

"Footprinting" describes assays in which ligand binding or structure formation protects polymers such as nucleic acids and proteins from either cleavage or modification; footprinting allows the accessibility of individual residues to be mapped in solution. Equilibrium and time-dependent footprinting links site-specific structural information with thermodynamic and kinetic transitions, respectively. The hydroxyl radical (*OH) is a uniquely insightful footprinting probe by virtue of it being among the most reactive chemical oxidants; it reports the solvent accessibility of reactive sites on macromolecules with as fine as a single residue resolution.

Distinct contribution of electrostatics, initial conformational ensemble, and macromolecular stability in RNA folding.

We distinguish the contribution of the electrostatic environment, initial conformational ensemble, and macromolecular stability on the folding mechanism of a large RNA using a combination of time-resolved "Fast Fenton" hydroxyl radical footprinting and exhaustive kinetic modeling. This integrated approach allows us to define the folding landscape of the L-21 Tetrahymena thermophila group I intron structurally and kinetically from its earliest steps with unprecedented accuracy. Distinct parallel pathways leading the RNA to its native form upon its Mg(2+)-induced folding are observed.