bioRxiv : the preprint server for biology最新文献

{"title":"Dietary protein source mediates colitis pathogenesis through bacterial modulation of bile acids.","authors":"Simon M Gray, Michael C Wood, Samantha C Mulkeen, Sunjida Ahmed, Shrey D Thaker, Bo Chen, William R Sander, Vladimira Bibeva, Xiaoyue Zhang, Jie Yang, Jeremy W Herzog, Shiying Zhang, Belgin Dogan, Kenneth W Simpson, R Balfour Sartor, David C Montrose","doi":"10.1101/2025.01.24.634824","DOIUrl":"https://doi.org/10.1101/2025.01.24.634824","url":null,"abstract":"<p><p>Evidence-based dietary recommendations for individuals with inflammatory bowel diseases (IBD) are limited. Red meat consumption is associated with increased IBD incidence and relapse in patients, suggesting that switching to a plant-based diet may limit gut inflammation. However, the mechanisms underlying the differential effects of these diets remain poorly understood. Feeding diets containing plant- or animal-derived proteins to murine colitis models revealed that mice given a beef protein (BP) diet exhibited the most severe colitis, while mice fed pea protein (PP) developed mild inflammation. The colitis-promoting effects of BP were microbially-mediated as determined by bacterial elimination or depletion and microbiota transplant studies. In the absence of colitis, BP-feeding reduced abundance of <i>Lactobacillus johnsonii</i> and <i>Turicibacter sanguinis</i> and expanded <i>Akkermansia muciniphila</i> , which localized to the mucus in association with decreased mucus thickness and quality. BP-fed mice had elevated primary and conjugated fecal bile acids (BAs), and taurocholic acid administration to PP-fed mice worsened colitis. Dietary psyllium protected against BP-mediated inflammation, restored BA-modulating commensals and normalized BA ratios. Collectively, these data suggest that the protein component of red meat may be responsible, in part, for the colitis-promoting effects of this food source and provide insight into dietary factors that may influence IBD severity.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11785241/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143081892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of systemic oxytocin and beta-3 receptor agonist (CL 316243) treatment on body weight and adiposity in male diet-induced obese rats.","authors":"Jared D Slattery, June R Rambousek, Edison Tsui, Mackenzie K Honeycutt, Matvey Goldberg, James L Graham, Tomasz A Wietecha, Tami Wolden-Hanson, Amber L Williams, Kevin D O'Brien, Peter J Havel, James E Blevins","doi":"10.1101/2024.09.27.615550","DOIUrl":"10.1101/2024.09.27.615550","url":null,"abstract":"<p><p>Previous studies have implicated hindbrain oxytocin (OT) receptors in the control of food intake and brown adipose tissue (BAT) thermogenesis. We recently demonstrated that hindbrain [fourth ventricle (4V)] administration of oxytocin (OT) could be used as an adjunct to drugs that directly target beta-3 adrenergic receptors (β3-AR) to elicit weight loss in diet-induced obese (DIO) rodents. What remains unclear is whether systemic OT can be used as an adjunct with the β3-AR agonist, CL 316243, to increase BAT thermogenesis and elicit weight loss in DIO rats. We hypothesized that systemic OT and β3-AR agonist (CL 316243) treatment would produce an additive effect to reduce body weight and adiposity in DIO rats by decreasing food intake and stimulating BAT thermogenesis. To test this hypothesis, we determined the effects of systemic (subcutaneous) infusions of OT (50 nmol/day) or vehicle (VEH) when combined with daily systemic (intraperitoneal) injections of CL 316243 (0.5 mg/kg) or VEH on body weight, adiposity, food intake and brown adipose tissue temperature (T _IBAT ). OT and CL 316243 monotherapy decreased body weight by 8.0±0.9% ( <i>P</i> <0.05) and 8.6±0.6% ( <i>P</i> <0.05), respectively, but OT in combination with CL 316243 produced more substantial weight loss (14.9±1.0%; <i>P</i> <0.05) compared to either treatment alone. These effects were associated with decreased adiposity, energy intake and elevated T _IBAT during the treatment period. The findings from the current study suggest that the effects of systemic OT and CL 316243 to elicit weight loss are additive and appear to be driven primarily by OT-elicited changes in food intake and CL 316243-elicited increases in BAT thermogenesis.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11537314/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142585458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EPISeg: Automated segmentation of the spinal cord on echo planar images using open-access multi-center data.","authors":"Rohan Banerjee, Merve Kaptan, Alexandra Tinnermann, Ali Khatibi, Alice Dabbagh, Christian Büchel, Christian W Kündig, Christine S W Law, Dario Pfyffer, David J Lythgoe, Dimitra Tsivaka, Dimitri Van De Ville, Falk Eippert, Fauziyya Muhammad, Gary H Glover, Gergely David, Grace Haynes, Jan Haaker, Jonathan C W Brooks, Jürgen Finsterbusch, Katherine T Martucci, Kimberly J Hemmerling, Mahdi Mobarak-Abadi, Mark A Hoggarth, Matthew A Howard, Molly G Bright, Nawal Kinany, Olivia S Kowalczyk, Patrick Freund, Robert L Barry, Sean Mackey, Shahabeddin Vahdat, Simon Schading, Stephen B McMahon, Todd Parish, Véronique Marchand-Pauvert, Yufen Chen, Zachary A Smith, Kenneth A Weber, Benjamin De Leener, Julien Cohen-Adad","doi":"10.1101/2025.01.07.631402","DOIUrl":"10.1101/2025.01.07.631402","url":null,"abstract":"<p><p>Functional magnetic resonance imaging (fMRI) of the spinal cord is relevant for studying sensation, movement, and autonomic function. Preprocessing of spinal cord fMRI data involves segmentation of the spinal cord on gradient-echo echo planar imaging (EPI) images. Current automated segmentation methods do not work well on these data, due to the low spatial resolution, susceptibility artifacts causing distortions and signal drop-out, ghosting, and motion-related artifacts. Consequently, this segmentation task demands a considerable amount of manual effort which takes time and is prone to user bias. In this work, we (i) gathered a multi-center dataset of spinal cord gradient-echo EPI with ground-truth segmentations and shared it on OpenNeuro [https://openneuro.org/datasets/ds005143/versions/1.3.0], and (ii) developed a deep learning-based model, EPISeg, for the automatic segmentation of the spinal cord on gradient-echo EPI data. We observe a significant improvement in terms of segmentation quality compared to other available spinal cord segmentation models. Our model is resilient to different acquisition protocols as well as commonly observed artifacts in fMRI data. The training code is available at [https://github.com/sct-pipeline/fmri-segmentation/], and the model has been integrated into the Spinal Cord Toolbox as a command-line tool.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11741348/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143019811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatiotemporal Complexity in the Psychotic Brain.","authors":"Qiang Li, Jingyu Liu, Godfrey D Pearlson, Jiayu Chen, Yu-Ping Wang, Jessica A Turner, Vince D Calhoun","doi":"10.1101/2025.01.14.632764","DOIUrl":"10.1101/2025.01.14.632764","url":null,"abstract":"<p><p>Psychotic disorders, such as schizophrenia and bipolar disorder, pose significant diagnostic challenges with major implications on mental health. The measures of resting-state fMRI spatiotemporal complexity offer a powerful tool for identifying irregularities in brain activity. To capture global brain connectivity, we employed information-theoretic metrics, overcoming the limitations of pairwise correlation analysis approaches. This enables a more comprehensive exploration of higher-order interactions and multiscale intrinsic connectivity networks (ICNs) in the psychotic brain. In this study, we provide converging evidence suggesting that the psychotic brain exhibits states of randomness across both spatial and temporal dimensions. To further investigate these disruptions, we estimated brain network connectivity using redundancy and synergy measures, aiming to assess the integration and segregation of topological information in the psychotic brain. Our findings reveal a disruption in the balance between redundant and synergistic information, a phenomenon we term brainquake in this study, which highlights the instability and disorganization of brain networks in psychosis. Moreover, our exploration of higher-order topological functional connectivity reveals profound disruptions in brain information integration. Aberrant information interactions were observed across both cortical and subcortical ICNs. We specifically identified the most easily affected irregularities in the sensorimotor, visual, temporal, default mode, and fronto-parietal networks, as well as in the hippocampal and amygdalar regions, all of which showed disruptions. These findings underscore the severe impact of psychotic states on multiscale critical brain networks, suggesting a profound alteration in the brain's complexity and organizational states.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11761638/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143049593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Solution biophysics identifies lipid nanoparticle non-sphericity, polydispersity, and dependence on internal ordering for efficacious mRNA delivery.","authors":"Marshall S Padilla, Sarah J Shepherd, Andrew R Hanna, Martin Kurnik, Xujun Zhang, Michelle Chen, James Byrnes, Ryann A Joseph, Hannah M Yamagata, Adele S Ricciardi, Kaitlin Mrksich, David Issadore, Kushol Gupta, Michael J Mitchell","doi":"10.1101/2024.12.19.629496","DOIUrl":"10.1101/2024.12.19.629496","url":null,"abstract":"<p><p>Lipid nanoparticles (LNPs) are the most advanced delivery system currently available for RNA therapeutics. Their development has accelerated since the success of Patisiran, the first siRNA-LNP therapeutic, and the mRNA vaccines that emerged during the COVID-19 pandemic. Designing LNPs with specific targeting, high potency, and minimal side effects is crucial for their successful clinical use. However, our understanding of how the composition and mixing method influences the structural, biophysical, and biological properties of the resulting LNPs remains limited, hindering the development of LNPs. Our lack of structural understanding extends from the physical and compositional polydispersity of LNPs, which render traditional characterization methods, such as dynamic light scattering (DLS), unable to accurately quantitate the physicochemical characteristics of LNPs. In this study, we address the challenge of structurally characterizing polydisperse LNP formulations using emerging solution-based biophysical methods that have higher resolution and provide biophysical data beyond size and polydispersity. These techniques include sedimentation velocity analytical ultracentrifugation (SV-AUC), field-flow fractionation followed by multi-angle light scattering (FFF-MALS), and size-exclusion chromatography in-line with synchrotron small-angle X-ray scattering (SEC-SAXS). Here, we show that the LNPs have intrinsic polydispersity in size, RNA loading, and shape, and that these parameters are dependent on both the formulation technique and lipid composition. Lastly, we demonstrate that these biophysical methods can be employed to predict transfection in human primary T cells, intravenous administration, and intramuscular administration by examining the relationship between mRNA translation and physicochemical characteristics. We envision that employing solution-based biophysical methods will be essential for determining LNP structure-function relationships, facilitating the creation of new design rules for LNPs.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11702722/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142974378","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Durable reconstitution of sinonasal epithelium by transplant of CFTR gene corrected airway stem cells.","authors":"Dawn T Bravo, Sriram Vaidyanathan, Jeannette Baker, Vrishti Sinha, Esmond Tsai, Pooya Roozdar, William W Kong, Patrick J Atkinson, Zara M Patel, Peter H Hwang, Vidya K Rao, Robert S Negrin, Jeffrey J Wine, Carlos Milla, Zachary M Sellers, Tushar J Desai, Matthew H Porteus, Jayakar V Nayak","doi":"10.1101/2025.01.24.634776","DOIUrl":"https://doi.org/10.1101/2025.01.24.634776","url":null,"abstract":"<p><p>Modulator agents that restore cystic fibrosis transmembrane conductance regulator (CFTR) function have revolutionized outcomes in cystic fibrosis, an incurable multisystem disease. Barriers exist to modulator use, making local CFTR gene and cell therapies attractive, especially in the respiratory tract. We used CRISPR to gene-correct CFTR in upper airway basal stem cells (UABCs) and show durable local engraftment into recipient murine respiratory epithelium. Interestingly, the human cells recapitulate the <i>in vivo</i> organization and differentiation of human sinus epithelium, with little expansion or contraction of the engrafted population over time, while retaining expression of the CFTR transgene. Our results indicate that human airway stem cell transplantation with locoregional restoration of CFTR function is a feasible approach for treating CF and potentially other diseases of the respiratory tract.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11785248/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143082844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RNAbpFlow: Base pair-augmented SE(3)-flow matching for conditional RNA 3D structure generation.","authors":"Sumit Tarafder, Debswapna Bhattacharya","doi":"10.1101/2025.01.24.634669","DOIUrl":"https://doi.org/10.1101/2025.01.24.634669","url":null,"abstract":"<p><strong>Motivation: </strong>Despite the groundbreaking advances in deep learning-enabled methods for bimolecular modeling, predicting accurate three-dimensional (3D) structures of RNA remains challenging due to the highly flexible nature of RNA molecules combined with the limited availability of evolutionary sequences or structural homology.</p><p><strong>Results: </strong>We introduce RNAbpFlow, a novel sequence- and base-pair-conditioned SE(3)-equivariant flow matching model for generating RNA 3D structural ensemble. Leveraging a nucleobase center representation, RNAbpFlow enables end-to-end generation of all-atom RNA structures without the explicit or implicit use of evolutionary information or homologous structural templates. Experimental results show that base pairing conditioning leads to broadly generalizable performance improvements over current approaches for RNA topology sampling and predictive modeling in large-scale benchmarking.</p><p><strong>Availability: </strong>RNAbpFlow is freely available at https://github.com/Bhattacharya-Lab/RNAbpFlow .</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11785242/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143083068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Striatal cell-type specific stability and reorganization underlying agency and habit.","authors":"Melissa Malvaez, Alvina Liang, Baila S Hall, Jacqueline R Giovanniello, Natalie Paredes, Julia Y Gonzalez, Garrett J Blair, Ana C Sias, Michael D Murphy, Wanyi Guo, Alicia Wang, Malika Singh, Nicholas K Griffin, Samuel P Bridges, Anna Wiener, Jenna S Pimenta, Sandra M Holley, Carlos Cepeda, Michael S Levine, H Tad Blair, Andrew M Wikenheiser, Kate M Wassum","doi":"10.1101/2025.01.26.634924","DOIUrl":"https://doi.org/10.1101/2025.01.26.634924","url":null,"abstract":"<p><p>Adaptive decision making requires agency, knowledge that actions produce particular outcomes. For well- practiced routines, agency is relinquished in favor of habit. Here, we asked how dorsomedial striatum D1 ⁺ and D2/A2A ⁺ neurons contribute to agency and habit. We imaged calcium activity of these neurons as mice learned to lever press with agency and formed habits with overtraining. Whereas many D1 ⁺ neurons stably encoded actions throughout learning and developed encoding of reward outcomes, A2A ⁺ neurons reorganized their encoding of actions from initial action-outcome learning to habit formation. Chemogenetic manipulations indicated that both D1 ⁺ and A2A ⁺ neurons support action-outcome learning, but only D1 ⁺ neurons enable the use of such agency for adaptive, goal-directed decision making. These data reveal coordinated dorsomedial striatum D1 ⁺ and A2A ⁺ function for the development of agency, cell-type specific stability and reorganization underlying agency and habit, and important insights into the neuronal circuits of how we learn and decide.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11785256/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143083116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Feature-Driven Whole-Tissue Imaging with Subcellular Resolution.","authors":"Jinlong Lin, Zach Marin, Xiaoding Wang, Hazel M Borges, Pierre-Emmanuel Y N'Guetta, Xuemei Luo, Baylee A Porter, Yuanyuan Xue, Md Torikul Islam, Tai Ngo, Arin B Aurora, Hu Zhao, Suzanne D Conzen, Sean J Morrison, Shuang Liang, Zhenyu Zhong, Lori L O'Brien, Kevin M Dean","doi":"10.1101/2025.01.23.634600","DOIUrl":"https://doi.org/10.1101/2025.01.23.634600","url":null,"abstract":"<p><p>Understanding how subcellular structures and events shape tissue-wide phenomena remains a central challenge in biology. We present Multiscale Cleared Tissue Axially Swept Light-Sheet Microscopy (MCT-ASLM), a platform combining cm-scale imaging with targeted high-resolution interrogation of intact tissues in human-guided or autonomous modes. Capable of capturing fields of view up to 21 mm at micron-scale resolution, MCT-ASLM can seamlessly transition to submicron (~300 nm) isotropic resolution for targeted imaging. This versatility enables comprehensive studies of hierarchical organization and spatially complex processes, including mapping neuronal circuits in rat brains, visualizing glomerular innervation in mouse kidneys, and examining metastatic tumor microenvironments. By bridging subcellular to tissue-level scales, MCT-ASLM offers a powerful method for unraveling how local events contribute to global biological phenomena.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11785217/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143082948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fexinidazole and Corallopyronin A target <i>Wolbachia</i> -infected sheath cells present in filarial nematodes.","authors":"Laura Chappell, Ricardo Peguero, William R Conner, Sommer Fowler, Brandon Cooper, Kenneth Pfarr, Achim Hoerauf, Sara Lustigman, Judy Sakanari, William Sullivan","doi":"10.1101/2025.01.23.634442","DOIUrl":"https://doi.org/10.1101/2025.01.23.634442","url":null,"abstract":"<p><p>The discovery of the endosymbiotic bacteria <i>Wolbachia</i> as an obligate symbiont of filarial nematodes has led to antibiotic-based treatments for filarial diseases. While lab and clinical studies have yielded promising results, recent animal studies reveal that <i>Wolbachia</i> levels may rebound following treatment with suboptimal doses of the antibiotic rifampicin. Previous work showed that a likely source of the bacterial rebound in females were dense clusters of <i>Wolbachia</i> in ovarian tissue. The number, size, and density of these <i>Wolbachia</i> clusters were not diminished despite antibiotic treatment. Here we define the cellular characteristics of the <i>Wolbachia</i> clusters in <i>Brugia pahangi</i> (wBp) and identify drugs that also target them. We have evidence that the <i>Wolbachia</i> clusters originate from newly formed sheath cells adjacent to the ovarian Distal Tip Cells. The dramatically enlarged volume of an infected sheath cell is strikingly similar to endosymbiont-induced bacteriocytes found in many insect species. Ultrastructural analysis reveals that the clustered <i>Wolbachia</i> present within the sheath cells exhibit a distinct morphology and form direct connections with the oocyte membrane and possibly the cytoplasm. This includes membrane-based channels providing a connection between <i>Wolbachia</i> -infected sheath cells and oocytes. We also determined that the <i>Wolbachia</i> within the sheath cells are either quiescent or replicating at a very low rate. Screens of known antibiotics and other drugs revealed that two drugs, Fexinidazole and Corallopyronin A, significantly reduced the number of clustered <i>Wolbachia</i> located within the sheath cells.</p>","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11785234/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143083011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}