Biomedical subjects

Ruslan Sadreyev

Publications and source records attributed to Ruslan Sadreyev.

6 recordsLinked to original sources

PubMed2026

LINE-1 repeats are a defining feature of the Xce.

During early development, female mammals inactivate one X chromosome to balance their X-linked gene dosage with males. While allelic choice is random in inbred mouse populations, choice can be significantly skewed in interstrain hybrids. The genetic basis of skewing has long been attributed to the mysterious "X chromosome controlling element(s)" (Xce) with different strengths among species, subspecies, and strains. When two X-chromosomes with different Xce strengths are inherited by offspring, the X chromosome with the stronger Xce will have a higher probability of remaining active. Here, we provide evidence that L1Tf repeats-a subfamily of long interspersed nuclear elements 1-plays a role in determining Xce strength. L1Tf elements form a condensed core within the inactive X (Xi) territory. Mouse strains with varying Xce strengths differ in the L1Tf copy number on the X chromosome, with the strength of the Xce allele being inversely related to L1Tf copy number. L1Tf expression mediates the Xce effect. However, in contrast to a prior report, L1Tf RNA does not coat the Xi. Rather, L1Tf promotes condensation of the Xi core. Intriguingly, L1Tfs recruit and sequester YY1 from active genes, accelerating XCI in cis. Thus, L1Tf copy number, expression, and binding of YY1 are key defining features of the Xce. We propose a model in which the Xce influences the choice of Xist alleles by promoting YY1 binding to the nucleation site for the initiation of Xist spreading.

Animals↗

PubMed2025

Pitavastatin, Procollagen Pathways, and Plaque Stabilization in Patients With HIV: A Secondary Analysis of the REPRIEVE Randomized Clinical Trial.

IMPORTANCE: In a mechanistic substudy of the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) randomized clinical trial, pitavastatin reduced noncalcified plaque (NCP) volume, but specific protein and gene pathways contributing to changes in coronary plaque remain unknown. OBJECTIVE: To use targeted discovery proteomics and transcriptomics approaches to interrogate biological pathways beyond low-density lipoprotein cholesterol (LDL-C), relating statin outcomes to reduce NCP volume and promote plaque stabilization among people with HIV (PWH). DESIGN, SETTING, AND PARTICIPANTS: This was a post hoc analysis of the double-blind, placebo-controlled, REPRIEVE randomized clinical trial. Participants underwent coronary computed tomography angiography (CTA), plasma protein analysis, and transcriptomic analysis at baseline and 2-year follow-up. The trial enrolled PWH from April 2015 to February 2018 at 31 US research sites. PWH without known cardiovascular diseases taking antiretroviral therapy and with low to moderate 10-year cardiovascular risk were eligible. Data analyses were conducted from October 2023 to February 2024. INTERVENTION: Oral pitavastatin calcium, 4 mg per day. MAIN OUTCOMES AND MEASURES: Relative change in plasma proteomics, transcriptomics, and noncalcified plaque volume among those receiving treatment vs placebo. RESULTS: Among 558 individuals (mean [SD] age, 51 [6] years; 455 male [82%]) included in the proteomics assessment, 272 (48.7%) received pitavastatin and 286 (51.3%) received placebo. After adjusting for false discovery rates, pitavastatin increased abundance of procollagen C-endopeptidase enhancer 1 (PCOLCE), neuropilin 1 (NRP-1), major histocompatibility complex class I polypeptide-related sequence A (MIC-A) and B (MIC-B), and decreased abundance of tissue factor pathway inhibitor (TFPI), tumor necrosis factor ligand superfamily member 10 (TRAIL), angiopoietin-related protein 3 (ANGPTL3), and mannose-binding protein C (MBL2). Among these proteins, the association of pitavastatin with PCOLCE (a rate-limiting enzyme of collagen deposition) was greatest, with an effect size of 24.3% (95% CI, 18.0%-30.8%; P < .001). In a transcriptomic analysis, individual collagen genes and collagen gene sets showed increased expression. Among the 195 individuals with plaque at baseline (88 [45.1%] taking pitavastatin, 107 [54.9%] taking placebo), changes in NCP volume were most strongly associated with changes in PCOLCE (%change NCP volume/log2-fold change = -31.9%; 95% CI, -42.9% to -18.7%; P < .001), independent of changes in LDL-C level. Increases in PCOLCE related most strongly to change in the fibro-fatty (<130 Hounsfield units) component of NCP (%change fibro-fatty volume/log2-fold change = -38.5%; 95% CI, -58.1% to -9.7%; P = .01) with a directionally opposite, although nonsignificant, increase in calcified plaque (%change calcified volume/log2-fold change = 34.4%; 95% CI, -7.9% to 96.2%; P = .12). CONCLUSIONS AND RELEVANCE: Results of this secondary analysis of the REPRIEVE randomized clinical trial suggest that PCOLCE may be associated with the atherosclerotic plaque stabilization effects of statins by promoting collagen deposition in the extracellular matrix transforming vulnerable plaque phenotypes to more stable coronary lesions. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02344290.

Humans↗

PubMed2003

Probabilistic scoring measures for profile-profile comparison yield more accurate short seed alignments.

MOTIVATION: The development of powerful automatic methods for the comparison of protein sequences has become increasingly important. Profile-to-profile comparisons allow for the use of broader information about protein families, resulting in more sensitive and accurate comparisons of distantly related sequences. A key part in the comparison of two profiles is the method for the calculation of scores for the position matches. A number of methods based on various theoretical considerations have been proposed. We implemented several previously reported scoring functions as well as our own functions, and compared them on the basis of their ability to produce accurate short ungapped alignments of a given length. RESULTS: Our results suggest that the family of the probabilistic methods (log-odds based methods and prof_sim) may be the more appropriate choice for the generation of initial 'seeds' as the first step to produce local profile-profile alignments. The most effective scoring systems were the closely related modifications of functions previously implemented in the COMPASS and Picasso methods.

Algorithms↗

PubMed2003

PCMA: fast and accurate multiple sequence alignment based on profile consistency.

UNLABELLED: PCMA (profile consistency multiple sequence alignment) is a progressive multiple sequence alignment program that combines two different alignment strategies. Highly similar sequences are aligned in a fast way as in ClustalW, forming pre-aligned groups. The T-Coffee strategy is applied to align the relatively divergent groups based on profile-profile comparison and consistency. The scoring function for local alignments of pre-aligned groups is based on a novel profile-profile comparison method that is a generalization of the PSI-BLAST approach to profile-sequence comparison. PCMA balances speed and accuracy in a flexible way and is suitable for aligning large numbers of sequences. AVAILABILITY: PCMA is freely available for non-commercial use. Pre-compiled versions for several platforms can be downloaded from ftp://iole.swmed.edu/pub/PCMA/.

Algorithms↗

PubMed2003

COMPASS: a tool for comparison of multiple protein alignments with assessment of statistical significance.

We present a novel method for the comparison of multiple protein alignments with assessment of statistical significance (COMPASS). The method derives numerical profiles from alignments, constructs optimal local profile-profile alignments and analytically estimates E-values for the detected similarities. The scoring system and E-value calculation are based on a generalization of the PSI-BLAST approach to profile-sequence comparison, which is adapted for the profile-profile case. Tested along with existing methods for profile-sequence (PSI-BLAST) and profile-profile (prof_sim) comparison, COMPASS shows increased abilities for sensitive and selective detection of remote sequence similarities, as well as improved quality of local alignments. The method allows prediction of relationships between protein families in the PFAM database beyond the range of conventional methods. Two predicted relations with high significance are similarities between various Rossmann-type folds and between various helix-turn-helix-containing families. The potential value of COMPASS for structure/function predictions is illustrated by the detection of an intricate homology between the DNA-binding domain of the CTF/NFI family and the MH1 domain of the Smad family.

Amino Acid Motifs↗

PubMedDate not supplied

COG4849 is a novel family of nucleotidyltransferases.

Only a minority of currently known protein families is characterized structurally. This makes homology-based structure modeling an essential instrument that can be viewed as the first approximation to experimental determination of protein structure. Using sequence similarity searches, we detected a distant similarity between a family of uncharacterized hypothetical proteins, COG4849, and the family of tRNA nucleotidyltransferases. The suggested remote homology between the N-terminal domain of COG4849 and the catalytic domain of tRNA nucleotidyltransferase was further supported by comparison of sequence profiles, methods for fold recognition and structure modeling. The combined multiple alignment of the two families reveals shared conservation of functionally important motifs and suggests the similarity in catalytic mechanisms of the performed reactions. Our results suggest that (i) the N-terminal domain of proteins from COG4849 shares structural similarity with the catalytic domain of tRNA nucleotidyltransferase, and (ii) this domain catalyzes the nucleotidyl transfer reaction involving two metal ions.

Bacterial Proteins↗