Biology subjects

Witt, C.

Publications and source records attributed to Witt, C..

4 recordsLinked to original sources

bioRxiv2026

Loss of the Y chromosome is transcriptionally silent in clear cell renal cell carcinoma and across cancer entities

Tumors in men often lose the Y chromosome. In some tumor types, this is predictive of poor outcome. Given the male predominance and high LOY frequency in clear cell renal cell carcinoma (ccRCC), we asked whether LOY might impact the transcriptome of ccRCC. We determined somatic Y chromosome status and performed differential expression analysis on tumor RNA-sequencing samples of two human ccRCC cohorts (TCGA-KIRC, CPTAC-ccRCC) and in an autochthonous murine ccRCC model with renal epithelium-specific deletion of Vhl, Trp53 and Rb1. We additionally derived five isogenic Y-deficient and five Y chromosome-retaining clones of the human ccRCC cell line 786-O. Across all three settings, transcriptional changes were largely restricted to the expected gene dosage effects of male-specific Y (MSY) and pseudoautosomal region (PAR) genes, without large effects on autosomal genes. At the pathway level, we identified a modest but reproducible response in the human cohorts, converging on cell cycle, ribosomal biogenesis and DNA repair genes. A pan-cancer meta-analysis across TCGA entities recovered the same pattern, with no autosomal gene showing a large consistent effect. In some entities, but not in ccRCC, cancer/testis antigen expression was higher in LOY tumors. We conclude that, apart from direct gene dosage, modest pathway-level shifts and altered silencing of cancer/testis antigens, LOY is transcriptionally silent in adult humans and mice. Y-chromosomal genes are therefore unlikely to act as transcriptional drivers of ccRCC and other cancer entities.

cancer biology↗

bioRxiv2026

Reverse genetics and comparative pathogenesis of Lone star virus.

Lone star virus (LSV) is a bandavirus first isolated from Amblyomma americanum ticks in the United States (U.S.) and is phylogenetically related to severe fever with thrombocytopenia syndrome virus (SFTSV), Heartland virus (HRTV), and Bhanja virus, each of which has been associated with severe human disease. In contrast to these better-characterized bandaviruses, LSV remains poorly studied, and its pathogenic potential is not well defined. Recent detection of LSV RNA in cerebrospinal fluid from an immunocompromised patient in Idaho, U.S., with fatal meningoencephalitis further highlights the need for experimental systems to investigate LSV biology. Here, we rescued recombinant (r) LSV from cloned cDNA and used it to characterize LSV. rLSV replicated similarly to the parental isolate in mammalian cells and caused rapid, systemic, and lethal disease in IFNAR-/- mice, with widespread detection of viral (v) RNA across multiple tissues, hepatic and splenic pathology, and induction of inflammatory cytokines. In contrast, C57BL/6J mice controlled infection and exhibited no clinical disease. To place LSV within a broader comparative framework, we generated rSFTSV from cloned cDNA and compared rLSV, rSFTSV, and HRTV in cell culture and IFNAR-/- mice. Our studies revealed distinct disease kinetics among these related tick-borne bandaviruses and showed that HRTV-induced immunity protected against homologous HRTV rechallenge and heterologous rSFTSV challenge, but not rLSV challenge. Together, these findings establish reverse-genetics platforms and small-animal models for comparative bandavirus studies, define key features of LSV pathogenesis, and place this neglected virus within a framework of related bandaviruses that differ in virulence and immunological overlap. ImportanceTick-borne bandaviruses include several viruses associated with severe human disease, yet many related viruses remain poorly characterized. Lone star virus (LSV) was first isolated from Amblyomma americanum ticks decades ago, but experimental tools and animal models to study LSV infection have been lacking. Here, we generated a recombinant LSV and used it to define the outcome of infection in immunocompromised and immunocompetent mice. We show that LSV can cause rapid, systemic, and lethal disease when type I interferon signaling is absent, whereas immunocompetent mice restrict infection and remain clinically normal. By comparing LSV with Heartland virus and severe fever with thrombocytopenia syndrome virus, we also show that related tick-borne bandaviruses differ in disease kinetics and immune protection. These findings provide foundational tools for studying LSV and highlight the importance of experimentally characterizing neglected tick-borne viruses before their pathogenic potential is fully understood.

microbiology↗

bioRxiv2025

History of divergence and gene flow shaping geographic variation in Andean warblers (Myioborus)

Studying how genetic variation is structured across space, and how it relates to divergence in phenotypic traits relevant to reproductive isolation, is important for our overall understanding of the speciation process. We used reduced-representation genomic data (ddRAD-seq) to examine patterns of genetic variation across the full distribution of an Andean warbler species complex (Myioborus ornatus-melanocephalus), which includes a known hybrid zone between two strikingly different plumage forms. Genetic structure largely reflects geographic variation in head plumage, some of which corresponds to major topographic barriers in the Andes. We also found evidence of isolation by distance shaping genetic patterns across the groups broad latitudinal range. We found that chrysops and bairdi, two taxa with marked plumage differences that have a known hybrid zone, were characterized by low overall genetic divergence. Based on our cline analyses of both plumage and genomic hybrid indices, this hybrid zone extends for approximately 250 km, where advanced generation hybrids are likely most common. We also identified a slight difference in the centers of the plumage and genomic clines, potentially suggesting the asymmetric introgression of chrysops-like plumage traits. By studying genetic variation in a phenotypically complex group distributed across a topographically complex area, which includes a hybrid zone, we were able to show how both geographic features and potentially sexually selected plumage traits may play a role in species formation in tropical mountains

evolutionary biology↗

bioRxiv2020

Behavior-specific occupancy patterns of Pinyon Jays (Gymnorhinus cyanocephalus) in three Great Basin study areas and significance for pinyon-juniper woodland management

AbstractThe Pinyon Jay is a highly-social, year-round inhabitant of pinyon-juniper woodlands in the western United States. Range-wide, Pinyon Jays have declined ~ 3 - 4% per year for at least the last half-century. At the same time, large acreages of pinyon-juniper woodland have been removed or thinned to improve habitat for Greater Sage-Grouse or other game species across much of the Great Basin, which is home to nearly half of the global population of Pinyon Jays. Occupancy patterns and habitat use of Pinyon Jays have not been well characterized across much of the species range, and obtaining this information is necessary for better understanding the causes of ongoing declines and determining useful conservation strategies. Our goal of this study was to identify the characteristics of areas used by Pinyon Jays for several critical life history components and to thereby facilitate the inclusion of Pinyon Jay conservation measures in the design of vegetation management projects. To accomplish this, we studied Pinyon Jays in three widely separated study areas using radio telemetry and direct observation, and measured key attributes of their locations and a separate set of randomly-selected control sites using the U. S. Forest Services Forest Inventory Analysis protocol. Data visualizations, non-metric dimension scaling ordinations, and logistic regressions of the resulting data indicated that Pinyon Jay occupancy was concentrated in a distinct subset of available pinyon-juniper woodland habitat, and further that Pinyon Jays used different habitats, arrayed along elevational and tree-cover gradients, for seed caching, foraging, and nesting. Caching was concentrated in low-elevation, relatively flat areas with low tree cover; foraging occurred at slightly higher elevations with moderate tree cover, and nesting was concentrated in somewhat higher areas with greater tree cover and higher stand density. All three of these Pinyon Jay behavior types were highly concentrated within the lower-elevation band of pinyon-juniper woodland close to the woodland-shrubland ecotone. Because woodland removal projects in the Great Basin are often concentrated in these same areas, it is critical to incorporate conservation measures informed by Pinyon Jay occupancy patterns into existing woodland management paradigms, protocols, and practices.

ecology↗