Biology subjects

Quinn, C.

Publications and source records attributed to Quinn, C..

8 recordsLinked to original sources

bioRxiv2026

An auditory advantage of Rdl-resistant mosquitoes may promote its persistence in urban environments

Despite dieldrin being discontinued, resistance mutations in the GABA-gated chloride channel RDL (Resistance to dieldrin) continue at high frequencies in natural malaria mosquitoes, suggesting a selective advantage. We showed that RDL modulates the mosquito auditory sensitivity. Because acoustic recognition is essential for mate acquisition, we hypothesized that resistance mutations confer a pleiotropic effect on mating success, with potential consequences for sexual selection. We provide laboratory evidence that resistance mutations enhance auditory and mating behaviours. We then conduct field collections in the city of Bangui (Central African Republic) and rural areas, revealing an association between Rdl resistance genotypes and urban settings, and within the city, with the noisiest locations. We also show decreased mating success of susceptible females with increasing noise levels, suggesting detrimental effects. Together, our findings support that Rdl resistance mutations enhance auditory function and mating success. We propose that this auditory advantage may contribute, together with other selective pressures such as cross-selection by other insecticides, to the persistence of these alleles in nature and may facilitate urban colonization by malaria vectors.

evolutionary biology↗

bioRxiv2025

Passive Acoustic Monitoring within the Northwest Forest Plan Area: 2024 Annual Report

Passive acoustic monitoring (PAM) has become the primary framework for assessing the status, distribution, and habitat associations of forest-dependent wildlife under the Northwest Forest Plan (NWFP). In 2024, the NWFP PAM program continued to operate as a fully integrated, range-wide monitoring network, building on deployments initiated in 2018 and now conducting surveys across approximately 24 million acres of federal land. Using a randomized 2+20% sampling design, more than 4,000 autonomous recording units generated over 2 million hours of acoustic data analyzed with convolutional neural networks, enabling statistically rigorous inference at regional and range-wide scales. This report summarizes 2024 field efforts and analytical advancements in the context of recent peer-reviewed and in-progress studies. Updated analyses confirm persistent, low occupancy of northern spotted owls (Strix occidentalis caurina), with detections concentrated in the Klamath Mountains and southern Cascades, consistent with long-term demographic declines. Range-wide models of barred owl (Strix varia) landscape use continue to show high occupancy across much of the NWFP area, reinforcing competitive displacement as the dominant driver of spotted owl range contraction. The PAM network also advanced monitoring of marbled murrelets (Brachyramphus marmoratus), with 2024 results supporting PAM as a cost-efficient alternative to traditional audio-visual surveys for assessing inland nesting habitat use in coastal forests. Beyond focal species, the program increasingly supports multi-taxa biodiversity monitoring through bioacoustic bycatch and soundscape analyses, linking species occurrence, habitat condition, and disturbance dynamics. Collectively, 2024 results demonstrate that PAM has reached operational maturity as the cornerstone of Phase II NWFP effectiveness monitoring. Sustaining adequate sampling effort and field capacity remains a challenge but essential, as reduced deployment intensity would increase uncertainty and weaken inference. Continued investment in PAM infrastructure and expertise is critical for informing adaptive management, supporting sustainable timber harvest, and evaluating ecosystem resilience under changing disturbance regimes.

ecology↗

bioRxiv2025

Passive Acoustic Monitoring within the Northwest Forest Plan Area: 2023 Annual Report

Here we document progress in implementing large-scale passive acoustic monitoring across the Northwest Forest Plan area to track population trends of northern spotted owls (Strix occidentalis caurina), barred owls (S. varia), marbled murrelets (Brachyramphus marmoratus), and a broad array of forest-adapted wildlife. In 2023, we deployed 4,012 autonomous recording units across 1,009 randomly selected 5-km{superscript 2} hexagons, generating nearly 2.2 million hours of recordings, representing approximately 1 petabyte of acoustic data. These data were processed with PNW-Cnet v5, the latest version of our convolutional neural network model, trained on 135 sound classes representing over 80 species and environmental sounds. Model performance demonstrated high precision for focal species and many additional taxa, substantially reducing manual review effort while enabling broad-scale biodiversity assessments. Results confirmed northern spotted owl detections in all 20% sample areas, with occupancy varying geographically and declining notably in the Tyee study area. Barred owls were widely detected, with the highest prevalence in Oregon and Washington and comparatively lower occupancy in California. Marbled murrelets were consistently detected in coastal areas, particularly the Olympic Peninsula and Oregon Coast Range. Beyond these focal species, PAM and PNW-Cnet generated robust datasets for a wide range of birds, mammals, and disturbance indicators, underscoring the value of random-site, multi-species monitoring. The 2023 field season marked the first full implementation of the 2% + 20% NWFP sampling design, expanding monitoring coverage while strengthening collaborations with federal and state partners. These efforts provide the foundation for long-term, cost-effective wildlife monitoring and inform conservation strategies in dynamic forest ecosystems.

ecology↗

bioRxiv2024

Obesity-associated MRAP2 variants impair multiple MC4R-mediated signaling pathways

The melanocortin-4 receptor (MC4R) is a G protein-coupled receptor expressed at hypothalamic neurons that has an important role in appetite suppression and food intake. Mutations in MC4R are the most common cause of monogenic obesity and can affect multiple signaling pathways including Gs-cAMP, Gq, ERK1/2, {beta}-arrestin recruitment, internalization and cell surface expression. The melanocortin-2 receptor accessory protein 2 (MRAP2), is a single-pass transmembrane protein that interacts with and regulates signaling by MC4R. Variants in MRAP2 have also been identified in overweight and obese individuals. However, functional studies that have only measured the effect of MRAP2 variants on MC4R-mediated cAMP signaling have produced inconsistent findings and most do not reduce MC4R function. Here we investigated the effect of twelve of these previously reported MRAP2 variants and showed that all variants that have been identified in overweight or obese individuals impair MC4R function. When expressed at equal concentrations, seven MRAP2 variants impaired MC4R-mediated cAMP signaling, while nine variants impaired IP3 signaling. Four mutations in the MRAP2 C-terminus affected internalization. MRAP2 variants had no effect on total or cell surface expression of either the MRAP2 or MC4R proteins. Structural models predicted that MRAP2 interacts with MC4R transmembrane helices 5 and 6, and mutations in two MRAP2 residues in putative contact sites impaired the ability of MRAP2 to facilitate MC4R signaling. In summary, our studies demonstrate that human MRAP2 variants associated with obesity impair multiple MC4R signaling pathways and that both Gs-cAMP and Gq-IP3 pathways should be assessed to determine variant pathogenicity.

molecular biology↗

bioRxiv2023

An interactive web application for exploring human plasma and fibroblast metabolomics data from patients with inborn errors of metabolism

Metabolomic profiling is instrumental in understanding the systemic and cellular impact of inborn errors of metabolism (IEMs), monogenic disorders caused by pathogenic genomic variants in genes involved in metabolism. This study encompasses untargeted metabolomics analysis of plasma from 474 individuals and fibroblasts from 67 subjects, incorporating healthy controls, patients with 65 different monogenic diseases, and numerous undiagnosed cases. We introduce a web application designed for the in-depth exploration of this extensive metabolomics database. The application offers a user-friendly interface for data review, download, and detailed analysis of metabolic deviations linked to IEMs at the level of individual patients or groups of patients with the same diagnosis. It also provides interactive tools for investigating metabolic relationships and offers comparative analyses of plasma and fibroblast profiles. This tool emphasizes the metabolic interplay within and across biological matrices, enriching our understanding of metabolic regulation in health and disease. As a resource, the application provides broad utility in research, offering novel insights into metabolic pathways and their alterations in various disorders.

bioinformatics↗

bioRxiv2022

Secreted folate receptor-gamma drives fibrogenesis in nonalcoholic steatohepatitis by amplifying TGFβ signaling in hepatic stellate cells

Hepatic fibrosis is the primary determinant of mortality in nonalcoholic steatohepatitis (NASH) patients. Antagonism of transforming growth factor {beta} (TGF{beta}), a master profibrogenic cytokine, is a promising therapeutic target that has not yet been translated into an effective therapy, due in part to the lack of animal models resembling the human phenotype of NASH. Here we have identified that soluble secreted folate receptor gamma (FOLR3), expressed in humans but not rodents, is a secreted protein that is elevated in livers of NASH subjects but not in subjects with nonalcoholic fatty liver, type II diabetes, or healthy subjects. FOLR3, based on global proteomics, was the most highly expressed NASH-specific protein and positively correlated with increasing fibrosis stages, suggesting an impact on activated hepatic stellate cells (HSCs), the key fibrogenic cell in the liver. Exposure of stellate cells to exogenous FOLR3 led to elevated extracellular matrix (ECM) protein production, an effect synergistic with TGF{beta}1. Structurally, FOLR3 interacts with serine protease HTRA1, which downregulates TGF{beta} signaling through the degradation of its receptor TGFBR2. Administration of human FOLR3 to mice induced severe bridging fibrosis and an ECM pattern resembling human NASH. Our study uncovers a novel role of FOLR3 in enhancing fibrosis and identifies FOLR3 as a potential therapeutic target in NASH fibrosis. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=143 SRC="FIGDIR/small/500829v1_ufig1.gif" ALT="Figure 1"> View larger version (27K): org.highwire.dtl.DTLVardef@1ac3ce3org.highwire.dtl.DTLVardef@d1945corg.highwire.dtl.DTLVardef@1632eb1org.highwire.dtl.DTLVardef@8e8d21_HPS_FORMAT_FIGEXP M_FIG C_FIG

biochemistry↗

bioRxiv2022

Structural stability of Human serum albumin is modified in rheumatoid arthritis

Differential scanning calorimetry (DSC) can interrogate changes in structure and/or concentration of the most abundant proteins in a biological sample via heat denaturation curves (HDCs). In blood serum for example, HDC changes are a result of either concentration or altered thermal stabilities for 7-10 proteins and has previously been shown capable of differentiating between sick and healthy human subjects. Here, we compare HDCs and proteomic profiles of 50 patients experiencing joint-inflammatory symptoms, 27 of which were clinically diagnosed with rheumatoid arthritis (RA). The HDC of all 50 subjects appeared significantly different from expected healthy curves, but comparison of additional differences between the RA the non-RA subjects allowed more specific understanding of RA samples. We used mass spectrometry (MS) to investigate the reasons behind the additional HDC changes in RA patients. The HDC differences do not appear to be directly related to differences in the concentrations of abundant serum proteins. Rather, the differences can be attributed to modified thermal stability of the most abundant protein, human serum albumin (HSA). By quantifying differences in the frequency of artificially induced post translational modifications (PTMs), we found that HSA in RA subjects had a much lower surface accessibility, indicating potential ligand or protein binding partners in certain regions that could explain the shift in HSA melting temperature in the RA HDCs. Several low abundance proteins were found to have significant changes in concentration in RA subjects and could be involved in or related to binding of HSA. Certain amino acid sites clusters were found to be less accessible in RA subjects, suggesting changes in HSA structure that may be related to changes in protein-protein interactions. These results all support a change in behavior of HSA which may give insight into mechanisms of RA pathology.

biochemistry↗

bioRxiv2021

CRISPR-mediated knock-in of transgenes into the malaria vector Anopheles funestus

The ability to introduce mutations, or transgenes, of choice to precise genomic locations has revolutionised our ability to understand how genes and organisms work. In many mosquito species that are vectors of various human disease, the advent of CRISPR genome editing tools has shed light on basic aspects of their biology that are relevant to their efficiency as disease vectors. This allows a better understanding of how current control tools work and opens up the possibility of novel genetic control approaches, such as gene drives, that deliberately introduce genetic traits into populations. Yet for the Anopheles funestus mosquito, a significant vector of malaria in sub-Saharan Africa and indeed the dominant vector species in many countries, transgenesis has yet to be achieved. We describe herein an optimised transformation system based on the germline delivery of CRISPR components that allows efficient cleavage of a previously validated genomic site and preferential repair of these cut sites via homology-directed repair (HDR), which allows introduction of exogenous template sequence, rather than end-joining repair. The rates of transformation achieved are sufficiently high that it should be able to introduce alleles of choice to a target locus, and recover these, without the need to include additional dominant marker genes. Moreover, the high rates of HDR observed suggest that gene drives, which employ an HDR-type mechanism to ensure their proliferation in the genome, may be well suited to work in An. funestus.

genetics↗