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Trubetskoy, D.

Publications and source records attributed to Trubetskoy, D..

2 recordsLinked to original sources

G4All: a database of experimentally confirmed G-quadruplex-forming sequences

G-quadruplexes (G4s) are non-canonical nucleic acid structures with critical roles in gene regulation, genomic stability, and disease, making them prime targets for therapeutic and biotechnological applications. However, the absence of a curated, centralized, experimentally validated repository of short (mostly synthetic) G4-forming sequences, paired with appropriate single-stranded or hairpin controls, has limited reproducibility and hindered progress in the field. Here, we introduce G4All, a comprehensive, curated database of G4-forming short DNA and RNA sequences, complemented by rigorously selected non-G4 controls, all studied under roughly similar experimental conditions (around 100 mM potassium ion at near neutral pH). G4All consolidates sequences validated by diverse experimental methods, including circular dichroism, NMR, UV spectroscopy, with standardized annotations for topology, thermal stability, and experimental conditions. By providing both positive and negative datasets, G4All enables rigorous comparative analyses, assay benchmarking, and the development of predictive models. The database supports a broad range of applications, from fundamental studies of G4 biophysics to the rational design of aptamers, as well as benchmarking prediction algorithms. Future developments will expand G4All to include user-submitted datasets and more RNA sequences. Freely accessible, G4All offers a searchable interface and downloadable datasets, establishing a community-driven hub to accelerate discovery and standardization in G4 research. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=81 SRC="FIGDIR/small/743020v1_ufig1.gif" ALT="Figure 1"> View larger version (30K): org.highwire.dtl.DTLVardef@111d015org.highwire.dtl.DTLVardef@74447corg.highwire.dtl.DTLVardef@13c5642org.highwire.dtl.DTLVardef@432469_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗

Activation of IL1A/IRAK1 axis and downstream proinflammatory signaling in healthy adult and neonatal African American skin

Differences in prevalence of inflammatory skin diseases including atopic dermatitis and psoriasis in African American (AA) versus White Non-Hispanic (WNH) population are well recognized. However, the underlying mechanisms are largely unknown. We previously observed significant differences in healthy AA skin transcriptome with differentially expressed genes (DEG) enriched for inflammation and cornification processes. Here we analyzed proteome in skin biopsies from healthy AA and WNH volunteers using Olink(R) Explore Inflammation 384 biomarker panel. Among proteins with higher expression in AA skin were IRAK1, IL1A, IL4, IL22RA1. IL1A binding to IL1R1 receptor is known to result in recruitment of adapter molecules such as IRAK1, and activation of downstream NF-{kappa}B and MAPK signaling. We confirmed NF-{kappa}B and ERK1/2 activation in AA skin by Western blot analysis of their phosphorylation at specific activating sites. Importantly, we observed similar differences between AA and WNH neonatal foreskin and between AA and WNH 3D skin organoids. Further analysis of DEG promoters by Gene Transcription Regulation Database (GTRD) pointed to NF-{kappa}B and AP1 as key transcription factors involved in AA DEG regulation. Overall, proinflammatory signaling in healthy AA skin starting early in childhood may contribute to the increased risk of certain inflammatory skin diseases within the AA population.

immunology↗