bioRxiv : the preprint server for biology最新文献

{"title":"Lung lipid deposition in pneumonias of different etiologies.","authors":"Daria M Potashnikova, Anna V Tvorogova, Alexey A Komissarov, Aleena A Saidova, Tatiana N Sotnikova, Valeria O Makarova, Eugene A Arifulin, Tatiana V Lipina, Olesya M Shirokova, Eugene S Melnikov, Tatiana A Rodina, Anna A Valyaeva, Anastasia A Zharikova, George O Zayratyants, Oleg V Zayratyants, Eugene V Sheval, Leonid B Margolis, Elena J Vasilieva","doi":"10.1101/2022.12.30.522299","DOIUrl":"10.1101/2022.12.30.522299","url":null,"abstract":"<p><p>Pneumonia is an acute respiratory disease of varying etiology that has drawn much attention during the COVID-19 pandemic. Among the many thoroughly studied aspects of pneumonia, lipid metabolism has not been sufficiently addressed. Here, we investigated lipid deposition in the <i>post mortem</i> lung specimens of patients who died from COVID-19 and non-COVID-19 pneumonias. We used semi-thin sections and cryosections stained with Sudan III to visualize lipid droplet deposition within cells and in the extracellular space, most notably in small lung vessels. Electron microscopy analysis of the ultrathin sections was used to confirm the homogeneous structure of the droplets. Morphometric analysis revealed that the area of lipid deposition was increased in pneumonia compared to control lung tissue. Likewise, it was increased in the macroscopically inflamed vs. the macroscopically intact area of the same pneumonia lung. The lipid profiling by chromato-mass spectrometry revealed that lipid droplet accumulation in pneumonia was associated with a specific fatty acid content of the inflamed lung tissue. The gene expression analysis pointed to changes of lipid metabolism in the inflamed lung tissue compared to control lungs. Taken together, our data indicate a number of morphologic and metabolic changes associated with inflammation and common for pneumonias of different etiologies that likely contribute to pneumonia pathogenesis. Therefore, targeting lipid metabolism can be considered a new therapeutic strategy.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9928036/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10716025","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":"A Molecular, Spatial, and Regulatory Atlas of the <i>Hydra vulgaris</i> Nervous System.","authors":"Hannah Morris Little, Abby S Primack, Jennifer Tsverov, Susanne Mühlbauer, Ben D Cox, Christina Busse, Sandra Schneid, Amber Louwagie, Jack F Cazet, Charles N David, Jeffrey A Farrell, Celina E Juliano","doi":"10.1101/2023.03.15.531610","DOIUrl":"10.1101/2023.03.15.531610","url":null,"abstract":"<p><p><i>Hydra vulgaris</i>, a cnidarian with a simple nerve net, is an emerging model for developmental, regenerative, and functional neuroscience. Its genetic tractability and capacity for whole-system imaging make it well suited for studying neuron replacement, regeneration, and neural circuit function. Here, we present the most comprehensive molecular and spatial characterization of the <i>H. vulgaris</i> nervous system to date. Using single-cell RNA sequencing, we identified eight neuron types, each defined by distinct neuropeptide expression, and further resolved these into fifteen transcriptionally distinct subtypes with unique spatial distributions and morphologies. To investigate the gene regulatory networks underlying neuronal differentiation, we applied trajectory inference, identified key transcription factors, and performed ATAC-seq on sorted neurons to map chromatin accessibility. All datasets are available through an interactive, user-friendly web portal to support broad use by the research community. Together, these resources provide a foundation for uncovering molecular mechanisms that govern nervous system development, homeostasis, and regeneration in <i>H. vulgaris</i>.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/fb/a4/nihpp-2023.03.15.531610v2.PMC10055148.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9347787","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":"WITHDRAWN: UBC13-mediated template switching promotes replication stress resistance.","authors":"Alexandra Hawks, Amy Bergmann, Tyler J McCraw, Jennifer M Mason","doi":"10.1101/2023.09.04.556280","DOIUrl":"10.1101/2023.09.04.556280","url":null,"abstract":"<p><p>The authors have withdrawn this manuscript because experiments completed with more sensitive detection methods have led to results inconsistent with the original data and conclusions of the original manuscript. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/95/1e/nihpp-2023.09.04.556280v2.PMC10508767.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41175161","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":"Ras-dependent activation of BMAL2 regulates hypoxic metabolism in pancreatic cancer.","authors":"Alvaro Curiel-Garcia, Sam R Holmstrom, Cristina Castillo, Carmine F Palermo, Steven A Sastra, Anthony Andren, Lorenzo Tomassoni, Li Zhang, Tessa Y S Le Large, Irina Sagalovskiy, Daniel R Ross, Winston Wong, Kaitlin Shaw, Jeanine Genkinger, Hanina Hibshoosh, Gulam A Manji, Alina C Iuga, Roland M Schmid, Kristen Johnson, Michael A Badgley, Pasquale Laise, Costas A Lyssiotis, Yatrik M Shah, Andrea Califano, H Carlo Maurer, Kenneth P Olive","doi":"10.1101/2023.03.19.533333","DOIUrl":"10.1101/2023.03.19.533333","url":null,"abstract":"<p><p>KRAS is the archetypal oncogenic driver of pancreatic cancer. To identify new modulators of KRAS activity in human pancreatic ductal adenocarcinoma (PDAC), we performed regulatory network analysis on a large collection of expression profiles from laser capture microdissected samples of PDAC and benign controls. We discovered that BMAL2, a member of the PAS family of transcription factors, promotes tumor initiation, progression, and post-resection survival, and is highly correlated with KRAS activity. Functional analysis of BMAL2 target genes suggested a role in regulating the hypoxia response, a hallmark of PDAC. Knockout of <i>BMAL2</i> in multiple human PDAC cell lines reduced cancer cell viability, invasion, and glycolysis, leading to broad dysregulation of cellular metabolism, particularly under hypoxic conditions. We find that BMAL2 directly regulates hypoxia-responsive target genes and is necessary for the stabilization of HIF1A under low oxygen conditions, while simultaneously destabilizing HIF2A. Notably, <i>in vivo</i> xenograft studies demonstrated that BMAL2 loss significantly impairs tumor growth and reduces tumor volume, underscoring its functional importance in tumor progression. We conclude that BMAL2 is a master transcriptional regulator of hypoxia responses in PDAC that works downstream of KRAS signaling, possibly serving as a long-sought molecular switch that distinguishes HIF1A- and HIF2A-dependent modes of hypoxic metabolism.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/18/7c/nihpp-2023.03.19.533333v1.PMC10055246.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9543699","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":"Failed Cellular Surveillance Enables Pathogenic Matrix Deposition in a <i>COL2A1</i> -Related Osteoarthritis.","authors":"Kathryn M Yammine, Sophia Mirda Abularach, Michael Xiong, Seo-Yeon Kim, Agata A Bikovtseva, Vincent L Butty, Richard P Schiavoni, John F Bateman, Shireen R Lamandé, Matthew D Shoulders","doi":"10.1101/2023.10.19.562780","DOIUrl":"10.1101/2023.10.19.562780","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Mutations in the &lt;i&gt;COL2A1&lt;/i&gt; gene, encoding procollagen-II, cause various chondrodysplasias, including precocious osteoarthritis with mild spondyloepiphyseal dysplasia engendered by the p.Arg719Cys substitution. The molecular mechanisms underlying these disorders remain incompletely understood, largely owing to the absence of models faithfully recapitulating the human disease. Here, we developed an &lt;i&gt;in vitro&lt;/i&gt; human cartilage model using isogenic induced pluripotent stem cell (iPSC) lines carrying either wild-type or Arg719Cys &lt;i&gt;COL2A1&lt;/i&gt; . Directed differentiation into chondrocytes yielded cartilage tissues that were analyzed by immunohistochemistry, electron microscopy, SDS-PAGE, and RNA-sequencing. Tissues derived from Arg719Cys heterozygotes displayed a deficient matrix, closely reflecting the human disease phenotype. Arg719Cys procollagen-II was excessively post-translationally modified and partially retained within the endoplasmic reticulum (ER), leading to ER distention. Notably, despite introduction of an aberrant cysteine residue-expected to engage redox-sensitive folding and quality control pathways-Arg719Cys procollagen-II was not detectably recognized by the ER proteostasis network. The resulting inability to mount a quality control response, including activation of the unfolded protein response, indicates a failure in cellular surveillance. As a result, malformed procollagen-II both accumulates intracellularly and is secreted, contributing to the deposition of a structurally compromised extracellular matrix that drives disease pathology. The iPSC-derived cartilage model presented here provides a genetically defined and expandable, human-based system for dissecting the mechanisms of failed proteostasis in collagenopathies. These findings shed light on the types of substitutions in procollagen that cells can or cannot recognize, and underscore the therapeutic potential of targeting cellular surveillance and collagen quality control pathways in &lt;i&gt;COL2A1&lt;/i&gt; -related disorders and beyond.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Significance: &lt;/strong&gt;The p.Arg719Cys substitution in &lt;i&gt;COL2A1&lt;/i&gt; is known to cause dominantly inherited precocious osteoarthritis with mild spondyloepiphyseal dysplasia, but its molecular pathogenesis remains poorly understood. Prior work suggests disrupted fibrillogenesis as the molecular etiology, yet phenotypically relevant human models are lacking. Here, we use human iPSC-derived cartilage to uncover how the Arg719Cys substitution alters procollagen-II folding, modification, trafficking, and matrix deposition. We observe hallmark disease phenotypes, including a sparse collagen-II matrix and distended endoplasmic reticulum (ER), consistent with intracellular accumulation of procollagen-II. Surprisingly, the mutant procollagen-II does not appear to be differentially engaged by the ER proteostasis network, despite the incorporation of an aberrant and apparently non-disulfide bond-forming Cys residue, suggesting a fundam","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10614947/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71415478","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":"Heme-Mediated Selection of Encapsulated <i>Streptococcus pneumoniae</i> in the Lungs by Oxidative Stress.","authors":"Babek Alibayov, Ana G Jop Vidal, Landon Murin, Anna Scasny, Kenichi Takeshita, Komal Beeton, Kristin S Edwards, Tracy Punshon, Brian P Jackson, Larry S McDaniel, Jorge E Vidal","doi":"10.1101/2023.11.14.567109","DOIUrl":"10.1101/2023.11.14.567109","url":null,"abstract":"<p><p><i>Streptococcus pneumoniae</i> (the pneumococcus) causes cytotoxicity and encapsulates within the lung parenchyma, leading to pneumococcal pneumonia. However, the underlying mechanisms remain unclear and likely involve multiple bacterial and host factors. We investigated the selection process of encapsulated pneumococci, a critical factor in lung damage during pneumococcal pneumonia. Our study revealed that pneumococci initially lack capsules but re-encapsulate upon reaching the alveoli. This process is driven by <i>S. pneumoniae</i>-derived hydrogen peroxide (Spn-H₂O₂), which oxidizes lung hemoglobin, leading to heme release and polymerized hemoglobin formation. Physiologically relevant levels of heme were found to promote the selection of encapsulated bacteria. Furthermore, encapsulation protects bacteria from intracellular heme toxicity, a defense absent in non-encapsulated strains. Ultrastructural analysis demonstrated interactions between hemoglobin and both encapsulated and non-encapsulated pneumococci in human sputum. These findings reveal a critical connection between oxidative stress-mediated lung damage and the selection of encapsulated pneumococci, suggesting potential therapeutic avenues by targeting these oxidative processes.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10680745/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138447302","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":"Protein phase change batteries drive innate immune signaling and cell fate.","authors":"Alejandro Rodriguez Gama, Tayla Miller, Shriram Venkatesan, Jeffrey J Lange, Jianzheng Wu, Xiaoqing Song, Dan Bradford, Malcolm Cook, Jay R Unruh, Randal Halfmann","doi":"10.1101/2023.03.20.533581","DOIUrl":"10.1101/2023.03.20.533581","url":null,"abstract":"<p><p>How minute pathogenic signals trigger decisive immune responses is a fundamental question in biology. Classical signaling often relies on ATP-driven enzymatic cascades, but innate immunity frequently employs death fold domain (DFD) self-assembly. The energetic basis of this assembly is unknown. Here, we show that specific DFDs function as energy reservoirs through metastable supersaturation. Characterizing all 109 human DFDs, we identified sequence-encoded nucleation barriers specifically in the central adaptors of inflammatory signalosomes, allowing them to accumulate far above their saturation concentration while remaining soluble and poised for activation. We demonstrate that the inflammasome adaptor ASC is constitutively supersaturated <i>in vivo</i>, retaining energy to power on-demand cell death. Swapping a non-supersaturable DFD in the apoptosome with a supersaturable one sensitized cells to sublethal stimuli. Mapping all DFD nucleating interactions revealed that supersaturated adaptors are specifically templated by other DFDs in their respective pathways, limiting deleterious crosstalk. Across human cell types, adaptor supersaturation strongly correlates with cell turnover, implicating this thermodynamic principle in the trade-off between immunity and longevity. Profiling homologues from fish, sponge, and bacteria, we find nucleation barriers to be ancestrally conserved. These findings reveal DFD adaptors as biological phase-change materials that function like batteries, storing and privatizing energy for life-or-death decisions.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10055258/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10045545","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":"Gene expression variation across genetically identical individuals predicts reproductive traits.","authors":"Amy K Webster, John H Willis, Erik Johnson, Peter Sarkies, Patrick C Phillips","doi":"10.1101/2023.10.13.562270","DOIUrl":"10.1101/2023.10.13.562270","url":null,"abstract":"<p><p>In recent decades, genome-wide association studies (GWAS) have been the major approach to understand the biological basis of individual differences in traits and diseases. However, GWAS approaches have limited predictive power to explain individual differences, particularly for complex traits and diseases in which environmental factors play a substantial role in their etiology. Indeed, individual differences persist even in genetically identical individuals, although fully separating genetic and environmental causation is difficult in most organisms. To understand the basis of individual differences in the absence of genetic differences, we measured two quantitative reproductive traits in 180 genetically identical young adult <i>Caenorhabditis elegans</i> roundworms in a shared environment and performed single-individual transcriptomics on each worm. We identified hundreds of genes for which expression variation was strongly associated with reproductive traits, some of which depended on individuals' historical environments and some of which was random. Multiple small sets of genes together were highly predictive of reproductive traits, explaining on average over half and over a quarter of variation in the two traits. We manipulated mRNA levels of predictive genes to identify a set of causal genes, demonstrating the utility of this approach for both prediction and understanding underlying biology. Finally, we found that the chromatin environment of predictive genes was enriched for H3K27 trimethylation, suggesting that gene expression variation may be driven in part by chromatin structure. Together, this work shows that individual, non-genetic differences in gene expression are both highly predictive and causal in shaping reproductive traits.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10592811/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49694486","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":"Amyloid β instigates cardiac neurotrophic signaling impairment, driving Alzheimer's associated heart disease.","authors":"Andrea Elia, Rebecca Parodi-Rullan, Rafael Vazquez-Torres, Ashley Carey, Sabzali Javadov, Silvia Fossati","doi":"10.1101/2023.07.11.548558","DOIUrl":"10.1101/2023.07.11.548558","url":null,"abstract":"<p><p>While a link between cardiovascular risk factors and increased Alzheimer's disease (AD) risk has been reported, it remains unclear whether AD pathology has a direct effect on cardiac function and myocardial innervation. AD and amyloidosis are known to impair neuronal function and affect brain neurotrophic factors (NGF and BDNF) expression. Amyloid aggregates and neuro-signaling impairments may also expose AD patients to peripheral nervous system deficits, promoting cardiac disorders. Here, we characterize cardiac physiology, amyloid pathology, neurotrophic factors loss, and the impoverishment of cardiac neuronal fibers in Tg2576-AD mice hearts, human cardiomyocytes in culture, and human AD post-mortem left ventricular (LV) heart tissue. We reveal that Tg2576 animals exhibit increased myocardial fibrosis, amyloid β (Aβ) deposition, and brain/heart-axis neurotrophic deficiencies, resulting in myocardial denervation and cardiac dysfunction. Aβ oligomers reduce BDNF expression in both human immortalized and iPSC-derived cardiomyocytes, by disrupting TrkB/CREB signaling. Analysis of human LV AD post-mortem tissue confirmed cell and animal results. Our findings elucidate a previously unknown mechanism of Aβ-induced cardiac neurotrophic signaling dysregulation, underscoring the relevance of heart degeneration in AD.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/7a/e3/nihpp-2023.07.11.548558v1.PMC10369880.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9922816","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":"Expanding salivary biomarker detection by creating a synthetic neuraminic acid sensor via chimeragenesis.","authors":"Samuel J Verzino, Sharona A Priyev, Valeria A Sánchez Estrada, Ali GholamianMogaddan, Gemma X Crowley, Alexandra Rutkowski, Amelia C Lam, Elizabeth S Nazginov, Paola Kotemelo, Agustina Bacelo, Jack D Flannery, Ksenya Gavrilov, Desiree T Sukhram, Frank X Vázquez, Javier F Juárez","doi":"10.1101/2024.06.13.598939","DOIUrl":"10.1101/2024.06.13.598939","url":null,"abstract":"<p><p>Accurate and timely diagnosis of oral squamous cell carcinoma (OSCC) is crucial in preventing its progression to advanced stages with poorer prognosis. As such, the construction of sensors capable of detecting previously established disease biomarkers for the early and non-invasive diagnosis of this and many other conditions has enormous therapeutic potential. In this work, we apply synthetic biology techniques for the development of a whole-cell biosensor (WCB) that leverages the physiology of engineered bacteria <i>in vivo</i> to promote the expression of an observable effector upon detection of a soluble molecule. To this end, we have constructed a bacterial strain expressing a novel chimeric transcription factor (Sphnx) for the detection of N-acetyl-D-neuraminic acid (Neu5Ac), a salivary biomolecule correlated with the onset of OSCC. This WCB serves as the proof-of-concept of a platform that can eventually be applied to clinical screening panels for a multitude of oral and systemic medical conditions whose biomarkers are present in saliva.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11195194/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141447942","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}