Biology subjects

Barton, E.

Publications and source records attributed to Barton, E..

3 recordsLinked to original sources

bioRxiv2025

Fibro-Adipogenic Progenitors require autocrine IGF-I in homeostatic and regenerating skeletal muscle

Fibro-Adipogenic Progenitors (FAPs) are mesenchymal stem cells that are vital for muscle homeostasis and regeneration but produce fibrosis and intramuscular fat under pathological conditions. Insulin-like Growth Factor-I (IGF-I) is a key regulator of muscle repair, satellite cell activity, macrophage polarization, and extracellular matrix (ECM) remodeling. We generated inducible FAP-specific Igf1 deficient (FID) mice to determine the necessity of FAP IGF-I. After BaCl2 injury, FID mice exhibited impaired muscle regeneration, with fewer Pax7+ cells, increased macrophage accumulation, smaller fibers, reduced ECM, and depressed FAP proliferation. Following glycerol injury, FID muscles exhibited reduced adipocyte accumulation. Primary FAPs isolated from injured FID muscles had blunted growth, upregulation of immune-regulatory genes and downregulation of ECM and cell proliferation genes, with delayed responses to fibrogenic and to adipogenic media. FAP property alterations were already present in homeostatic muscle, indicated by scRNASeq, with decreased indices of protein translation and ECM production as well as increased markers of senescence, confirmed in vivo and in vitro. Overall, FAP IGF-I is a critical autocrine factor, with further paracrine consequences for muscle regenerative capacity.

molecular biology↗

bioRxiv2025

Vertical transmission of chronic wasting disease in free-ranging white-tailed deer populations

Chronic wasting disease (CWD) is a fatal neurodegenerative disease affecting cervids across North America, Northern Europe, and Asia. Disease transmission among cervids has historically been attributed to direct animal-to-animal contact with secreta (saliva, blood, urine, and feces) containing the infectious agent, and indirect contact with the agent shed to the environment in these bodily components. Mounting evidence provides another mechanism of CWD transmission, that from mother-to-offspring, including during pregnancy (vertical transmission). Here we describe the detection of the infectious CWD agent and prion seeding in fetal and reproductive tissues collected from healthy-appearing free-ranging white-tailed deer (Odocoileus virginianus) from multiple U.S. states by mouse bioassay and in vitro prion amplification assays. This is the first report of the infectious agent in several in utero derived fetal and maternal-fetal reproductive tissues, providing evidence that CWD infections are propagated within gestational fetal tissues of white-tailed deer populations. This work confirms previous experimental and field findings in several cervid species supporting vertical transmission as a mechanism of CWD transmission and helps to further explain the facile dissemination of this disease among captive and free-ranging cervid populations.

neuroscience↗

bioRxiv2019

Tomato yellow leaf curl virus V2 protein plays a critical role in the nuclear export of V1 protein and viral systemic infection

Geminiviruses are an important group of circular, single-stranded DNA viruses that cause devastating diseases in crops. Geminiviruses replicate their genomic DNA in the nucleus. The newly-synthesized viral DNA is subsequently transported to the cytoplasm, moved to adjacent cells through plasmodesmata with the help of viral movement proteins, and, ultimately, moved long-distance to establish systemic infection. Thus, the nucleocytoplasmic transportation is crucial for a successful infection by geminiviruses. For Tomato yellow leaf curl virus (TYLCV), the V1 protein is known to bind and shuttle viral genomic DNA, but the role of V2 protein in this process is still unclear. Here, we report that the nucleus-localized V1 protein dramatically decreases when co-expressed with V2 protein, and that V2-facilitated nuclear export of V1 protein depends on host exportin- and a specific V1-V2 interaction. Chemical inhibition of exportin- or a substitutions at cysteine 85 of V2 protein, which abolishes the V1-V2 interaction, blocks the promoted redistribution of V1 protein to the perinuclear region and the cytoplasm. When the V2C85S mutation is incorporated into a TYLCV infectious clone, the TYLCV-C85S causes delayed onset of very mild symptoms compared to wild-type TYLCV, indicating that the V1-V2 interaction and, thus, V2-mediated nuclear export of V1 protein is crucial for viral spread and systemic infection. Our data point to a critical role of the V2 protein in promoting the nuclear export of the V1 protein, likely by promoting V1-mediated nucleocytoplasmic transportation of TYLCV genomic DNA, and in turn, promoting viral systemic infection.\n\nAuthor summaryAs both replication and the transcription of geminiviruses occur in the nucleus, transportation of the viral genomic DNA into and out of the nucleus of the infected cells is essential for a successful infection cycle. However, the nuclear export of geminiviruses is still little known and even less is known about the process for monopartite geminiviruses. We use TYLCV, a typical monopartite begomovirus in the family Geminiviridae, to examine the nucleocytoplasmic transportation. In this study, we found TYLCV V2 is able to redistribute the nucleus-localized V1 protein to the perinuclear region. Moreover, the nuclear export of V1 protein is dependent on the V1-V2 interaction and host exportin-. Blocking the V1-V2 interaction impeded the V2-mediated V1 protein redistribution and decrease TYLCV infection efficiency with delayed and mild symptoms. This report shows us a new explanation for the role of V2 in the nuclear export of V1 protein and TYLCV viral systemic infection.

pathology↗