bioRxiv最新文献

{"title":"EPHA1 and EPHB4 tyrosine kinase receptors regulate epithelial morphogenesis","authors":"Noémie Lavoie, Anaëlle Scribe, François J. M. Chartier, Karim Ghani, Alexandra Jetté, Sara L. Banerjee, Manuel Caruso, Mélanie Laurin, A. Freywald, S. Elowe, P. Laprise, Nicolas Bisson","doi":"10.1101/2024.07.15.603563","DOIUrl":"https://doi.org/10.1101/2024.07.15.603563","url":null,"abstract":"Organ formation and homeostasis require the coordination of cell-cell adhesion, epithelial cell polarity and orientation of cell division to organize epithelial tissue architecture. We have previously identified proximity protein networks acting downstream of members of the EPH family of tyrosine kinase receptors and found within these networks an enrichment of components associated with cell morphogenesis and cell-cell junctions. Here, we show that two EPH receptors, EPHA1 and EPHB4, are localized to the basolateral domain of Caco-2 cells in spheroidal cultures. Depletion of either EPHA1 or EPHB4 disrupts spheroid morphogenesis, without affecting cell polarity, but via randomizing mitotic spindle orientation during cell division. Strikingly, EPHA1 and EPHB4 exert this function independently of their catalytic activity but still requiring EFN ligand binding. Consistent with this, the most abundantly expressed EPHB4 ligand in Caco-2 cells, EFNB2, is also compartmentalized at the basolateral domain in spheroids, and is required for epithelial morphogenesis. Taken together, our data reveal a new role for EPHRs in epithelial morphogenesis.","PeriodicalId":9124,"journal":{"name":"bioRxiv","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141641133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The flow state is not accompanied by frontal-midline theta activity: An EEG investigation of more than 700 video gameplay sessions","authors":"Hirotaka Sugino, Takuya Ideriha, Ryoichiro Yamazaki, Junichi Ushiyama","doi":"10.1101/2024.07.11.603158","DOIUrl":"https://doi.org/10.1101/2024.07.11.603158","url":null,"abstract":"People sometimes experience a “flow state”—characterized by hyperfocus, time distortion, and loss of self-awareness—during sports or video gameplay. Previous neuropsychological studies using simple laboratory tasks have reported that the flow state is associated with activation in the frontal lobe, reflected in theta (4–7 Hz) band rhythmic neural activity in medial prefrontal regions (frontal-midline theta [FMT] activity). However, the findings of previous studies might be problematic because they did not appropriately capture the neural activity associated with the flow state for the following reasons: 1) they used unfamiliar and unmotivating tasks; 2) they defined the neural basis of the flow state as neural activity occurring during tasks of optimal difficulty, disregarding trial-to-trial variations in subjective experience of the flow state; 3) the duration of the experiment or the number of trials was not sufficient to capture the rare experience of flow; or 4) they ignored individual differences in neural activities related to flow experiences. Thus, we examined the relationship between the flow state and FMT activity, recorded via scalp electroencephalography, in an experimental paradigm that addressed these four issues. First, participants played their favorite competitive video games, which they had been routinely playing. Second, task difficulty was kept as uniform as possible across trials by employing rank matching to directly examine the correlation between subjective flow level and FMT activity across trials. Third, to address the concern regarding the low frequency of the flow experience, more than 100 trials were completed over 10 days by each participant. Lastly, we adopted a within-participant statistical approach to examine individual differences in the nature of the flow experience. The results showed no correlation between FMT activity and the degree of subjective flow in six out of seven participants, contrary to previous reports. Our results challenge the conventional view that frontal lobe activity, as reflected in FMT activity, is instrumental in entering into the flow state.","PeriodicalId":9124,"journal":{"name":"bioRxiv","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141641298","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IFNγ initiates TLR9-dependent autoimmune hepatitis in DNase II deficient mice","authors":"Kaiyuan Hao, K. M. Gao, Melissa Strauss, Sharon Subramanian, Ann Marshak-Rothstein","doi":"10.1101/2024.07.10.602775","DOIUrl":"https://doi.org/10.1101/2024.07.10.602775","url":null,"abstract":"Patients with biallelic hypomorphic mutation in DNASE2 develop systemic autoinflammation and early-onset liver fibrosis. Prior studies showed that Dnase2-/- Ifnar-/- double knockout (DKO) mice develop Type I IFN-independent liver inflammation, but immune mechanisms were unclear. We now show that DKO mice recapitulate many features of human autoimmune hepatitis (AIH), including periportal and interstitial inflammation and fibrosis and elevated ALT. Infiltrating cells include CD8+ tissue resident memory T cells, type I innate lymphoid cells, and inflammatory monocyte/macrophage cells that replace the Kupffer cell pool. Importantly, TLR9 expression by bone marrow-derived cells is required for the the development of AIH. TLR9 is highly expressed by inflammatory myeloid cells but not long-lived Kupffer cells. Furthermore, the initial recruitment of TLR9 expressing monocytes and subsequent activation of lymphocytes requires IFNγ signaling. These findings highlight a critical role of feed forward loop between TLR9 expressing monocyte-lineage cells and IFNg producing lymphocytes in autoimmune hepatitis.","PeriodicalId":9124,"journal":{"name":"bioRxiv","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141641762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Resident memory T cells in dirty mice suppress innate cell activation and infiltration into the skin following stimulation with alarmins","authors":"Meaghan E. Story, Laura K. Ferris, A. Mathers","doi":"10.1101/2024.07.11.602963","DOIUrl":"https://doi.org/10.1101/2024.07.11.602963","url":null,"abstract":"Trm cells are sequestered at barrier tissues as a swift first line defense against peripheral reinfections in both antigen dependent and antigen independent bystander modes. Trm cells are also capable of mediating autoimmune diseases, such as psoriasis, wherein autoreactive Trm cells are aberrantly activated. To quickly combat infections, activated Trm cells can stimulate the influx and activation of memory T cells and innate immune cells. However, there is significant heterogeneity in the inflammatory responses that Trm cell populations can induce, specifically in the activation of the innate profile. Most studies to date have utilized a reductionist approach to examine single Trm populations, specific pathogens, and defined tissues. Herein, we adopted a more holistic approach utilizing barrier-free ‘dirty’ mice to profile activated innate cells attracted to the skin in the presence of quiescent cutaneous Trm cells. Notably, dirty mice are a more human predictive model due to having a diverse microbial experience that leads to the development of a complete complement of Trm cells in the skin. We demonstrate that in the dirty mouse model mice have a significant reduction in cutaneous neutrophils and monocytes compared to SPF mice following local treatment with two separate innate stimuli. These findings reveal that cutaneous Trm cells have the capacity to temper the innate immune response and further substantiate the implication that Trm cells are heterogenous in their functions depending in large part on their tissue residency. However, in an autoimmune microenvironment Trm cells are capable of recruiting innate cells to the site of an exposure to a damage-associated molecular pattern. Likely due to the imbalance of IL-17 and IFN-γ.","PeriodicalId":9124,"journal":{"name":"bioRxiv","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141641923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of leg immobilization and recovery resistance training on skeletal muscle-molecular markers in previously resistance trained versus untrained adults","authors":"J. M. Michel, Joshua S. Godwin, Daniel L. Plotkin, Mason Mcintosh, Madison L. Mattingly, Philip Agostinelli, Breanna J. Mueller, Derick A. Anglin, Alexander C. Berry, Marina Meyer Vega, Autumn A. Pipkin, Matt S. Stock, Zachary A. Graham, Harsimran S. Baweja, C. B. Mobley, M. Bamman, Michael D Roberts","doi":"10.1101/2024.07.12.603321","DOIUrl":"https://doi.org/10.1101/2024.07.12.603321","url":null,"abstract":"We sought to examine how resistance training (RT) status in young healthy individuals, either well-trained (T, n=10 (8 males)) or untrained (UT, n=11 (8 males)), affected muscle size and molecular markers with leg immobilization followed by recovery RT. All participants underwent two weeks of left leg immobilization via the use of crutches and a locking leg brace. After this two-week period, all participants underwent eight weeks (3 d/week) of knee extensor focused progressive RT. Vastus lateralis (VL) ultrasound-derived thickness and muscle cross-sectional area were measured at baseline (PRE), immediately after disuse (MID), and after RT (POST) with VL muscle biopsies collected at these time points. T and UT presented lower ultrasound derived VL size (cross-sectional area and thickness) values at MID versus PRE (p≤0.001), and values increased in both groups from MID to POST (p<0.05); however, VL size increased from PRE to POST in UT only (p<0.001). Mean and type II myofiber cross-sectional area (fCSA) values demonstrated a main effect of time where PRE and POST were greater than MID (p<0.05) and main effect of training status where T was greater than UT (P≤0.012). In both groups, satellite cell number was not affected by leg immobilization but increased in response to RT (p≤0.014), with T being greater than UT across all time points (p=0.004). Additionally, ribosome content (total RNA) decreased (p=0.010) from PRE to MID while the endoplasmic reticulum stress proteins (BiP, Xbp1s, and CHOP) increased from MID to POST regardless of training status. Finally, the phosphorylation states of mechanistic target of rapamycin complex-1 signaling proteins were not significantly altered for either group throughout the intervention. In conclusion, immobilization-induced muscle atrophy and recovery RT hypertrophy outcomes are similar between UT and T participants, and the lack of molecular signature differences between groups supports these findings. However, these data are limited to younger adults undergoing non-complicated disuse. Thus, further investigation to determine the impact of training status on prolonged leg immobilization models mirroring current medical protocols (e.g., following orthopedic injury and surgery) is warranted.","PeriodicalId":9124,"journal":{"name":"bioRxiv","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141642951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ExPOSE: A comprehensive toolkit to perform expansion microscopy in plant protoplast systems","authors":"Kevin L. Cox, Sarah A. Pardi, Lily O’Connor, Anastasiya Klebanovych, David Huss, Dmitri A. Nusinow, Blake C. Meyers, Kirk J. Czymmek","doi":"10.1101/2024.07.12.603300","DOIUrl":"https://doi.org/10.1101/2024.07.12.603300","url":null,"abstract":"Expansion microscopy (ExM) achieves nanoscale imaging by physical expansion of fixed biological tissues embedded in a swellable hydrogel, enhancing the resolution of any optical microscope several-fold. While ExM is commonly used in animal cells and tissues, there are few plant specific protocols. Protoplasts are a widely used cell system across plant species, especially in studying biomolecule localization. Here, we present an approach to achieve robust expansion of plant protoplasts, termed Expansion microscopy in plant PrOtoplast SystEms (ExPOSE). We demonstrate that coupling ExPOSE with other imaging techniques, immunofluorescence and in situ hybridization chain reaction to visualize proteins and mRNAs, respectively, greatly enhances the spatial resolution of endogenous biomolecules. Additionally, in this study, we tested the effectiveness and versatility of this technique to observe biomolecular condensates in Arabidopsis protoplasts and transcription factors in maize protoplasts at increased resolution. ExPOSE can be relatively inexpensive, fast, and simple to implement.","PeriodicalId":9124,"journal":{"name":"bioRxiv","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141640613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The evolution of an individual-like dispersive stage in colonial siphonophores","authors":"Maciej K. Mańko, C. Munro, L. Leclère","doi":"10.1101/2024.07.15.603641","DOIUrl":"https://doi.org/10.1101/2024.07.15.603641","url":null,"abstract":"Evolutionary transitions between individual and colonial organisms remain enigmatic. Siphonophores, abundant pelagic cnidarians, exhibit a complex colony structure composed of repeated individual (zooid) clusters called cormidia. Many siphonophores release their posterior-most cormidia as independent fragments known as eudoxids, ensuring sexual reproduction. However, the mechanisms of eudoxid production and its evolutionary origins are unknown. Using live imaging, immunohistochemistry and pharmacological inhibition we provide a mechanistic understanding of eudoxid formation. We demonstrate that eudoxid release is controlled by a dedicated muscle and involves tissue remodeling, leading to the formation of an integrated dispersive unit with specific behaviors and a different buoyancy. We show that eudoxids and parental colonies often have different spatial or temporal distributions, suggesting niche partitioning. We infer that eudoxids evolved once through the concomitant evolution of multiple cormidium subparts. This study reveals how the acquisition of an individual-like dispersal stage, through muscle evolution and colony modification, contributed to the ecological success of a primary carnivore in marine planktonic ecosystems. Teaser Co-option of a muscle in siphonophores enabled life cycle complexification and ecological diversification","PeriodicalId":9124,"journal":{"name":"bioRxiv","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141643231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prophage-DB: A comprehensive database to explore diversity, distribution, and ecology of prophages","authors":"Etan Dieppa-Colón, Cody Martin, Karthik Anantharaman","doi":"10.1101/2024.07.11.603044","DOIUrl":"https://doi.org/10.1101/2024.07.11.603044","url":null,"abstract":"Background Viruses that infect prokaryotes (phages) constitute the most abundant group of biological agents, playing pivotal roles in microbial systems. They are known to impact microbial community dynamics, microbial ecology, and evolution. Efforts to document the diversity, host range, infection dynamics, and effects of bacteriophage infection on host cell metabolism are extremely underexplored. Phages are classified as virulent or temperate based on their life cycles. Temperate phages adopt the lysogenic mode of infection, where the genome integrates into the host cell genome forming a prophage. Prophages enable viral genome replication without host cell lysis, and often contribute novel and beneficial traits to the host genome. Current phage research predominantly focuses on lytic phages, leaving a significant gap in knowledge regarding prophages, including their biology, diversity, and ecological roles. Results Here we develop and describe Prophage-DB, a database of prophages, their proteins, and associated metadata that will serve as a resource for viral genomics and microbial ecology. To create the database, we identified and characterized prophages from genomes in three of the largest publicly available databases. We applied several state-of-the-art tools in our pipeline to annotate these viruses, cluster and taxonomically classify them, and detect their respective auxiliary metabolic genes. In total, we identify and characterize over 350,000 prophages and 35,000 auxiliary metabolic genes. Our prophage database is highly representative based on statistical results and contains prophages from a diverse set of archaeal and bacterial hosts which show a wide environmental distribution. Conclusion Prophages are particularly overlooked in viral ecology and merit increased attention due to their vital implications for microbiomes and their hosts. Here, we created Prophage-DB to advance our comprehension of prophages in microbiomes through a comprehensive characterization of prophages in publicly available genomes. We propose that Prophage-DB will serve as a valuable resource for advancing phage research, offering insights into viral taxonomy, host relationships, auxiliary metabolic genes, and environmental distribution.","PeriodicalId":9124,"journal":{"name":"bioRxiv","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141643624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Closing the gap in the clinical adoption of computational pathology: a standardized, open-source framework to integrate deep-learning algorithms into the laboratory information system","authors":"Miriam Angeloni, Davide Rizzi, Simon Schoen, Alessandro Caputo, Francesco Merolla, Arndt Hartmann, F. Ferrazzi, Filippo Fraggetta","doi":"10.1101/2024.07.11.603091","DOIUrl":"https://doi.org/10.1101/2024.07.11.603091","url":null,"abstract":"Digital pathology (DP) has revolutionized cancer diagnostics, allowing the development of deep-learning (DL) models supporting pathologists in their daily work and contributing to the improvement of patient care. However, the clinical adoption of such models remains challenging. Here we describe a proof-of-concept framework that, leveraging open-source DP software and Health Level 7 (HL7) standards, allows the integration of DL models in the clinical workflow. Development and testing of the workflow were carried out in a fully digitized Italian pathology department. A Python-based server-client architecture was implemented to interconnect the anatomic pathology laboratory information system (AP-LIS) with an external artificial intelligence decision support system (AI-DSS) containing 16 pre-trained DL models through HL7 messaging. Open-source toolboxes for DL model deployment, including WSInfer and WSInfer-MIL, were used to run DL model inference. Visualization of model predictions as colored heatmaps was performed in QuPath. As soon as a new slide is scanned, DL model inference is automatically run on the basis of the slide’s tissue type and staining. In addition, pathologists can initiate the analysis on-demand by selecting a specific DL model from the virtual slides tray. In both cases the AP-LIS transmits an HL7 message to the AI-DSS, which processes the message, runs DL model inference, and creates the appropriate type of colored heatmap on the basis of the employed classification model. The AI-DSS transmits model inference results to the AP-LIS, where pathologists can visualize the output in QuPath and/or directly from the virtual slides tray. The developed framework supports multiple DL toolboxes and it is thus suitable for a broad range of applications. In addition, this integration workflow is a key step to enable the future widespread adoption of DL models in pathology diagnostics.","PeriodicalId":9124,"journal":{"name":"bioRxiv","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141641815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatial Transcriptomics and Single-Nucleus Multi-omics Analysis Revealing the Impact of High Maternal Folic Acid Supplementation on Offspring Brain Development","authors":"Xiguang Xu, Yu Lin, Liduo Yin, Priscila da Silva Serpa, Benjamin Conacher, Christina Pacholac, Francisco Carvallo, Terry Hrubec, Shannon Farris, Kurt Zimmerman, Xiaobin Wang, Hehuang Xie","doi":"10.1101/2024.07.12.603269","DOIUrl":"https://doi.org/10.1101/2024.07.12.603269","url":null,"abstract":"Folate, an essential vitamin B9, is crucial for diverse biological processes including neurogenesis. Folic acid (FA) supplementation during pregnancy is a standard practice for preventing neural tube defects (NTDs). However, concerns are growing over the potential risks of excessive maternal FA intake. Here, we employed mouse model and spatial transcriptomics and single-nucleus multi-omics approaches to investigate the impact of high maternal FA supplementation during the periconceptional period on offspring brain development. Maternal high FA supplementation affected gene pathways linked to neurogenesis and neuronal axon myelination across multiple brain regions, as well as gene expression alterations related to learning and memory in thalamic and ventricular regions. Single-nucleus multi-omics analysis revealed that maturing excitatory neurons in the dentate gyrus (DG) are particularly vulnerable to high maternal FA intake, leading to aberrant gene expressions and chromatin accessibility in pathways governing ribosomal biogenesis critical for synaptic formation. Our findings provide new insights into specific brain regions, cell types, gene expressions and pathways that can be affected by maternal high FA supplementation.","PeriodicalId":9124,"journal":{"name":"bioRxiv","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141641064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}