Biology subjects

Wiscovitch-Russo, R.

Publications and source records attributed to Wiscovitch-Russo, R..

5 recordsLinked to original sources

bioRxiv2026

A Metabolic Enzyme, Pyruvate Carboxylase, Functions as a Sequence-Selective Small RNA Sensor for Antiviral Immunity

Interleukin-27 (IL-27) is an anti-HIV cytokine that induces 14 novel microRNAs (miRNAs) in primary CD4(+) T cells. We previously reported that transfection of two of these miRNA mimics, miRTC10 and miRTC14 into human primary macrophages, differentially induced interferon (IFN)-2, -8, -13, and -{lambda}1 expression. However, the mechanism underlying this activation remains unclear. Here, we demonstrate that miRTC14 does not directly target canonical IFN-regulatory genes but instead engages with pyruvate carboxylase (PC) and laboratory of genetics and physiology-2 (LGP2/DHX58) as direct binding partner proteins. Functional analysis revealed that miRTC14 transfection induces IFN expression by more than 100-fold (p<0.001), whereas PC or LGP2 depletion by siRNAs markedly attenuated this response (50-100-fold reduction, p<0.01). Reconstitution of PC and LGP2 in deficient HEK293 cells restored miRTC14-driven IFN induction. Notably, IFN activation depended on sequence features at the duplex termini. However, PC-miRTC14-LGP2 axis activates TBK1-dependent phosphorylation of IRF3/7, similarly to canonical RNA sensors (RIG-I/MDA5), but this process induced differential IFN subtype. These findings establish PC as a miRNA-binding protein and define a previously unrecognized RNA-sensing mechanism, linking metabolic enzymes to RNA sequence-dependent innate immunity. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=189 SRC="FIGDIR/small/735367v2_ufig1.gif" ALT="Figure 1"> View larger version (42K): org.highwire.dtl.DTLVardef@ea70d3org.highwire.dtl.DTLVardef@1953a73org.highwire.dtl.DTLVardef@305f16org.highwire.dtl.DTLVardef@1b2daff_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical Abstract:C_FLOATNO microRNA sequence-dependent activation of innate immunity by pyruvate carboxylase (PC). PC-miRTC14-LGP2 axis induces TBK1 phosphorylation via an as-yet-unidentified adapter(s). The activated TBK1 (p-TBK1) subsequently phosphorylates IRF3 and/or IRF7 leading to selective IFN subtypes (IFN-2, IFN-8, IFN-13, and IFN-{lambda}1). (Created in BioRender. Kariyawasam, U. (2027) https://BioRender.com/u82s04p) C_FIG

immunology↗

bioRxiv2026

Biological signatures of history: Examination of composite biomes and Y chromosome analysis from da Vinci-associated cultural artifacts

Cultural heritage objects can accumulate DNA from materials, environments, and repeated human contact, but biomolecular profiling of such items is constrained by nondestructive sampling requirements, ultra-low biomass, and high contamination risk. Here we present a minimally invasive workflow that integrates gentle swab collection, low- input whole-metagenome sequencing, taxonomic profiling, and Y-chromosome analyses to recover "biological signatures of history" from Renaissance-era artwork and archival correspondence associated with ancestors of Leonardo da Vinci. Across artifacts, we recovered heterogeneous mixtures of microbial and eukaryotic DNA (including bacteria, fungi, plants, and viruses) consistent with composite "biomes" that reflect differences in substrate, storage, conservation treatments, and handling. Multivariate comparisons show reproducible sample-to-sample separations. In parallel, we assessed human Y-chromosome signal using a panel of [~]90,000 phylogenetically informative markers and partial Y-STR profiling where feasible. Across multiple independent swabs from Leonardo da Vinci-associated items, the obtained Y chromosome marker data suggested assignments withing the broader E1b1/E1b1b clade. However, the control samples also indicate mixed contributions consistent with modern handling and other sources. Together, these data demonstrate the feasibility as well as limitations of combining metagenomics and human DNA marker analysis for cultural heritage science, providing a baseline workflow for future conservation science studies and hypothesis-driven investigations of provenance, authentication and handling history.

genomics↗

bioRxiv2025

Respiratory exposure to inert particulate matter during pregnancy leads to oxidative stress and cardiac proteome remodeling

Withdrawal StatementThe authors have withdrawn this manuscript because upon peer review major revisions have been identified as needed to ensure that the conclusions are in par with the presented data. Current studies are ongoing to provide a more complete version of the manuscript for peer review publication. Therefore, the authors do not wish this work to be cited as reference for the project in its current form. If you have any questions, please contact the corresponding author.

molecular biology↗

bioRxiv2024

Multiomic Insights into Human Health: Gut Microbiomes of Hunter-Gatherer, Agropastoral, and Western Urban Populations

Societies with exposure to preindustrial diets exhibit improved markers of health. Our study used a comprehensive multi-omic approach to reveal that the gut microbiome of the Ju/hoansi hunter-gatherers, one of the most remote KhoeSan groups, exhibit a higher diversity and richness, with an abundance of microbial species lost in the western population. The Ju/hoansi microbiome showed enhanced global transcription and enrichment of complex carbohydrate metabolic and energy generation pathways. The Ju/hoansi also show high abundance of short-chain fatty acids that are associated with health and optimal immune function. In contrast, these pathways and their respective species were found in low abundance or completely absent in Western populations. Amino acid and fatty acid metabolism pathways were observed prevalent in the Western population, associated with biomarkers of chronic inflammation. Our study provides the first in-depth multi-omic characterization of the Ju/hoansi microbiome, revealing uncharacterized species and functional pathways that are associated with health.

genomics↗

bioRxiv2022

A multiomics analysis of direct interkingdom dynamics between influenza A virus and Streptococcus pneumoniae uncovers host-independent changes to bacterial virulence fitness

BackgroundFor almost a century, it has been recognized that influenza A virus (IAV) infection can promote the development of secondary bacterial infections (SBI) mainly caused by Streptococcus pneumoniae (Spn). Recent observations have shown that IAV is able to directly bind to the surface of Spn. To gain a foundational understanding of how direct IAV-Spn interaction alters bacterial biological fitness we employed combinatorial multi-omic and molecular approaches. ResultsHere we show IAV significantly remodels the global transcriptome, proteome and phosphoproteome profiles of Spn independently of host effectors. We identified Spn surface proteins that interact with IAV proteins (hemagglutinin, nucleoprotein, and neuraminidase). In addition, IAV was found to directly modulate expression of Spn virulence determinants such as pneumococcal surface protein A, pneumolysin, and factors associated with antimicrobial resistance among many others. Metabolic pathways were significantly altered leading to changes in Spn growth rate. IAV was also found to drive Spn capsule shedding and the release of pneumococcal surface proteins. Released proteins were found to be involved in evasion of innate immune responses and actively reduced human complement hemolytic and opsonizing activity. IAV also led to phosphorylation changes in Spn proteins associated with metabolism and bacterial virulence. Validation of proteomic data showed significant changes in Spn galactose and glucose metabolism. Furthermore, supplementation with galactose rescued bacterial growth and promoted bacterial invasion, while glucose supplementation led to enhanced pneumolysin production and lung cell apoptosis. ConclusionsHere we demonstrate that IAV can directly modulate Spn biology without the requirement of host effectors and support the notion that inter-kingdom interactions between human viruses and commensal pathobionts can promote bacterial pathogenesis and microbiome dysbiosis.

microbiology↗