bioRxiv : the preprint server for biology最新文献

{"title":"Connectional axis of individual functional variability: Patterns, structural correlates, and relevance for development and cognition.","authors":"Hang Yang, Guowei Wu, Yaoxin Li, Xiaoyu Xu, Jing Cong, Haoshu Xu, Yiyao Ma, Yang Li, Runsen Chen, Adam Pines, Ting Xu, Valerie Jill Sydnor, Theodore D Satterthwaite, Zaixu Cui","doi":"10.1101/2023.03.08.531800","DOIUrl":"10.1101/2023.03.08.531800","url":null,"abstract":"<p><p>The human cerebral cortex exhibits intricate interareal functional synchronization at the macroscale, with substantial individual variability in these functional connections. However, the spatial organization of functional connectivity (FC) variability across the human connectome edges and its significance in cognitive development remain unclear. Here, we identified a connectional axis in the edge-level FC variability. The variability declined continuously along this axis from within-network to between-network connections, and from the edges linking association networks to those linking the sensorimotor and association networks. This connectional axis of functional variability is associated with spatial pattern of structural connectivity variability. Moreover, the connectional variability axis evolves in youth with an increasing flatter axis slope. We also observed that the slope of connectional variability axis was positively related to the performance in the higher-order cognition. Together, our results reveal a connectional axis in functional variability that is linked with structural connectome variability, refines during development, and is relevant to cognition.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c8/8f/nihpp-2023.03.08.531800v1.PMC10028904.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9186956","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":"Next-Generation Breast Organoids Capture Human Organogenesis with High-Resolution Live Imaging.","authors":"Gat Rauner, Nicole C Traugh, Colin J Trepicchio, Meadow E Parrish, Kenan Mushayandebvu, Charlotte Kuperwasser","doi":"10.1101/2023.10.02.560364","DOIUrl":"10.1101/2023.10.02.560364","url":null,"abstract":"<p><p>Organoids have emerged as a powerful tool for modeling tissue growth and diseases. In this study, we introduce a groundbreaking organotypic culture technique that replicates the morphology, scale, and heterogeneity of human breast tissue, and includes a mesenchymal-like stromal component. A standout feature of this approach is the use of long-term live imaging at high temporal resolution to directly observe stem cell dynamics during organogenesis, from single cells to mature organ tissue. The system is adaptable for high throughput applications and allows for genetic manipulation of the cells. Real-time imaging of ex-vivo tissue formation reveals a non-canonical process of ductal-lobular morphogenesis and branching, and de-novo generation of a supportive stroma. Incorporating patient-derived single cells from multiple donors offers an enhanced representation of the spectrum of individual responses and the impacts of distinct exposures. While developed for breast tissue, the principles of this technology can serve as a model for the development of similar systems in other tissues, where organoids do not merely reproduce the tissue, but where their regeneration can also be observed and studied. In addition, this model provides a quantitative experimental system to study mechanisms of embryogenesis, development, and tissue organization where biomechanics plays an important role.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10592625/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49694436","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":"Animal septins contain functional transmembrane domains.","authors":"Jenna A Perry, Michael E Werner, Shizue Omi, Bryan W Heck, Paul S Maddox, Manos Mavrakis, Amy S Maddox","doi":"10.1101/2023.11.20.567915","DOIUrl":"10.1101/2023.11.20.567915","url":null,"abstract":"<p><p>Septins, a conserved family of filament-forming proteins, contribute to eukaryotic cell division, polarity, and membrane trafficking. Septins scaffold other proteins to cellular membranes, but it is not fully understood how septins associate with membranes. We identified and characterized an isoform of <i>Caenorhabditis elegans</i> septin UNC-61 that was predicted to contain a transmembrane domain (TMD). The TMD isoform is expressed in a subset of tissues where the known septins were known to act, and TMD function was required for tissue integrity of the egg-laying apparatus. We found predicted TMD-containing septins across much of opisthokont phylogeny and demonstrated that the TMD-containing sequence of a primate TMD-septin is sufficient for localization to cellular membranes. Together, our findings reveal a novel mechanism of septin-membrane association with profound implications for septin dynamics and regulation.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10690161/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138479601","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":"<i>Inversions Can Accumulate Balanced Sexual Antagonism: Evidence from Simulations and</i> Drosophila <i>Experiments</i>.","authors":"Christopher S McAllester, John E Pool","doi":"10.1101/2023.10.02.560529","DOIUrl":"10.1101/2023.10.02.560529","url":null,"abstract":"<p><p>Chromosomal inversion polymorphisms can be common, but the causes of their persistence are often unclear. We propose a model for the maintenance of inversion polymorphism, which requires that some variants contribute antagonistically to two phenotypes, one of which has negative frequency-dependent fitness. These conditions yield a form of frequency-dependent disruptive selection, favoring two predominant haplotypes segregating alleles that favor opposing antagonistic phenotypes. An inversion associated with one haplotype can reduce the fitness load incurred by generating recombinant offspring, reinforcing its linkage to the haplotype and enabling both haplotypes to accumulate more antagonistic variants than expected otherwise. We develop and apply a forward simulator to examine these dynamics under a tradeoff between survival and male display. These simulations indeed generate inversion-associated haplotypes with opposing sex-specific fitness effects. Antagonism strengthens with time, and can ultimately yield karyotypes at surprisingly predictable frequencies, with striking genotype frequency differences between sexes and between developmental stages. To test whether this model may contribute to well-studied yet enigmatic inversion polymorphisms in <i>Drosophila melanogaster</i>, we track inversion frequencies in laboratory crosses to test whether they influence male reproductive success or survival. We find that two of the four tested inversions show significant evidence for the tradeoff examined, with <i>ln(3R)K</i> favoring survival and <i>ln(3L)Ok</i> favoring male reproduction. In line with the apparent sex-specific fitness effects implied for both of those inversions, <i>ln(3L)Ok</i> was also found to be less costly to the viability and/or longevity of males than females, whereas <i>ln(3R)K</i> was more beneficial to female survival. Based on this work, we expect that balancing selection on antagonistically pleiotropic traits may provide a significant and underappreciated contribution to the maintenance of natural inversion polymorphism.</p>","PeriodicalId":72407,"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/PMC10592935/pdf/nihpp-2023.10.02.560529v2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49694590","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":"Programming megakaryocytes to produce engineered platelets for delivering non-native proteins.","authors":"Farhana Islam, Shwan B Javdan, Mitchell R Lewis, James D Craig, Han Wu, Tara L Deans","doi":"10.1101/2023.10.13.562311","DOIUrl":"10.1101/2023.10.13.562311","url":null,"abstract":"<p><p>Platelets are anucleate cells naturally filled with secretory granules that store large amounts of protein to be released in response to certain physiological conditions. Cell engineering can endow platelets with the ability to deliver non-native proteins by modifying them as they develop during the cell fate process. This study presents a strategy to efficiently generate mouse platelets from pluripotent stem cells and demonstrates their potential as bioengineered protein delivery platforms. By modifying megakaryocytes, the progenitor cells of platelets, we successfully engineered platelets capable of packaging and delivering non-native proteins. These engineered platelets can offer flexible delivery platforms to release non-native proteins in a controlled manner upon activation when packaged into α-granules or deliver active enzymes to genetically alter recipient cells. Our findings highlight platelets as a promising tool for protein delivery in cell therapy applications.</p>","PeriodicalId":72407,"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/PMC10592833/pdf/nihpp-2023.10.13.562311v1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49694667","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":"Neural substrates of cold nociception in <i>Drosophila</i> larva.","authors":"Atit A Patel, Albert Cardona, Daniel N Cox","doi":"10.1101/2023.07.31.551339","DOIUrl":"10.1101/2023.07.31.551339","url":null,"abstract":"<p><p>Metazoans detect and differentiate between innocuous (non-painful) and/or noxious (harmful) environmental cues using primary sensory neurons, which serve as the first node in a neural network that computes stimulus specific behaviors to either navigate away from injury-causing conditions or to perform protective behaviors that mitigate extensive injury. The ability of an animal to detect and respond to various sensory stimuli depends upon molecular diversity in the primary sensors and the underlying neural circuitry responsible for the relevant behavioral action selection. Recent studies in <i>Drosophila</i> larvae have revealed that somatosensory class III multidendritic (CIII md) neurons function as multimodal sensors regulating distinct behavioral responses to innocuous mechanical and nociceptive thermal stimuli. Recent advances in circuit bases of behavior have identified and functionally validated <i>Drosophila</i> larval somatosensory circuitry involved in innocuous (mechanical) and noxious (heat and mechanical) cues. However, central processing of cold nociceptive cues remained unexplored. We implicate multisensory integrators (Basins), premotor (Down-and-Back) and projection (A09e and TePns) neurons as neural substrates required for cold-evoked behavioral and calcium responses. Neural silencing of cell types downstream of CIII md neurons led to significant reductions in cold-evoked behaviors and neural co-activation of CIII md neurons plus additional cell types facilitated larval contraction (CT) responses. Further, we demonstrate that optogenetic activation of CIII md neurons evokes calcium increases in these neurons. Finally, we characterize the premotor to motor neuron network underlying cold-evoked CT and delineate the muscular basis of CT response. Collectively, we demonstrate how <i>Drosophila</i> larvae process cold stimuli through functionally diverse somatosensory circuitry responsible for generating stimulus-specific behaviors.</p>","PeriodicalId":72407,"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://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/52/50/nihpp-2023.07.31.551339v1.PMC10418107.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10055686","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":"Cell autonomous polarization by the planar cell polarity signaling pathway.","authors":"Alexis T Weiner, Silas Boye Nissen, Kaye Suyama, Bomsoo Cho, Gandhy Pierre-Louis, Jeffrey D Axelrod","doi":"10.1101/2023.09.26.559449","DOIUrl":"10.1101/2023.09.26.559449","url":null,"abstract":"<p><p>Planar Cell Polarity (PCP) signaling polarizes epithelial cells in a plane orthogonal to their apical-basal axis. A core PCP signaling module segregates two distinct molecular subcomplexes to opposite sides of cells and coordinates the direction of polarization between neighboring cells. Homodimers of the atypical cadherin Flamingo are thought to scaffold these subcomplexes and are required for intercellular polarity signaling. Feedback is required for polarization, but whether feedback requires intercellular and/or intracellular pathways is unknown, and traditional genetic tools have limited utility in dissecting these mechanisms. Using novel tools, we show that cells lacking Flamingo, or bearing a homodimerization-deficient Flamingo, do polarize, indicating that functional PCP subcomplexes form and segregate cell-autonomously. We identify feedback pathways and propose a competitive binding-based asymmetry amplifying mechanism that each operate cell-autonomously. The intrinsic logic of PCP signaling is therefore more similar to that in single cell polarizing systems than was previously recognized.</p>","PeriodicalId":72407,"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://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/bc/3e/nihpp-2023.09.26.559449v1.PMC10557733.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41123282","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":"Direct detection of deformation modes on varying length scales in active biopolymer networks.","authors":"Samantha Stam, Margaret L Gardel, Kimberly L Weirich","doi":"10.1101/2023.05.15.540780","DOIUrl":"10.1101/2023.05.15.540780","url":null,"abstract":"<p><p>Correlated flows and forces that emerge from active matter orchestrate complex processes such as shape regulation and deformations in biological cells and tissues. The active materials central to cellular mechanics are cytoskeletal networks, where molecular motor activity drives deformations and remodeling. Here, we investigate deformation modes in contractile actin networks driven by the molecular motor myosin II through quantitative fluorescence microscopy. We examine the deformation anisotropy at different length scales in networks of sparsely cross-linked and bundled actin. In sparsely cross-linked networks, we find myosin-dependent biaxial buckling modes across length scales. Interestingly, both long and short-wavelength buckling may contribute to network contractility. In cross-linked bundled networks, uniaxial contraction predominates on long length scales, while the uniaxial or biaxial nature of the deformation depends on bundle microstructure at shorter length scales. The anisotropy of deformations may provide insight to the mechanical origins of contractility in actin networks and regulation of collective behavior in a variety of active materials.</p>","PeriodicalId":72407,"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://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/55/eb/nihpp-2023.05.15.540780v1.PMC10245561.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9638838","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":"Spatial periodicity in grid cell firing is explained by a neural sequence code of 2-D trajectories.","authors":"R G Rebecca, Giorgio A Ascoli, Nate M Sutton, Holger Dannenberg","doi":"10.1101/2023.05.30.542747","DOIUrl":"10.1101/2023.05.30.542747","url":null,"abstract":"<p><p>Spatial periodicity in grid cell firing has been interpreted as a neural metric for space providing animals with a coordinate system in navigating physical and mental spaces. However, the specific computational problem being solved by grid cells has remained elusive. Here, we provide mathematical proof that spatial periodicity in grid cell firing is the only possible solution to a neural sequence code of 2-D trajectories and that the hexagonal firing pattern of grid cells is the most parsimonious solution to such a sequence code. We thereby provide a likely teleological cause for the existence of grid cells and reveal the underlying nature of the global geometric organization in grid maps as a direct consequence of a simple local sequence code. A sequence code by grid cells provides intuitive explanations for many previously puzzling experimental observations and may transform our thinking about grid cells.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e7/c4/nihpp-2023.05.30.542747v1.PMC10312530.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9820138","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":"QPPLab: A generally applicable software package for detecting, analyzing, and visualizing large-scale quasiperiodic spatiotemporal patterns (QPPs) of brain activity.","authors":"Nan Xu, Behnaz Yousefi, Nmachi Anumba, Theodore J LaGrow, Xiaodi Zhang, Shella Keilholz","doi":"10.1101/2023.09.25.559086","DOIUrl":"10.1101/2023.09.25.559086","url":null,"abstract":"<p><p>Quasi-periodic patterns (QPPs) are prominent spatiotemporal brain dynamics observed in functional neuroimaging data, reflecting the alternation of high and low activity across brain regions and their propagation along cortical gradients. QPPs have been linked to neural processes such as attention, arousal fluctuations, and cognitive function. Despite their significance, existing QPP analysis tools are limited by study-specific parameters and complex workflows. To address these challenges, we present <b><i>QPPLab</i></b> , an open-source MATLAB-based toolbox for detecting, analyzing, and visualizing QPPs from fMRI time series. QPPLab integrates correlation-based iterative algorithms, supports customizable parameter settings, and features automated workflows to simplify analysis. Processing times vary depending on dataset size and the selected mode, with the fast detection mode completing analyses that can be 4-6 times faster than the robust detection mode. Results include spatiotemporal templates of QPPs, sliding correlation time courses, and functional connectivity maps. By reducing manual parameter adjustments and providing user-friendly tools, QPPLab enables researchers to efficiently study QPPs across diverse datasets and species, advancing our understanding of intrinsic brain dynamics.</p>","PeriodicalId":72407,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10557593/pdf/nihpp-2023.09.25.559086v1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41172029","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}