bioRxivPub Date : 2024-07-16DOI: 10.1101/2024.07.15.603503
Kohei Ito, Yutaro Ito
{"title":"Comparative genomic analysis of Latilactobacillus sakei strains provides new insights into their association with different niche adaptations","authors":"Kohei Ito, Yutaro Ito","doi":"10.1101/2024.07.15.603503","DOIUrl":"https://doi.org/10.1101/2024.07.15.603503","url":null,"abstract":"Latilactobacillus sakei, a lactic acid bacterium in diverse environments such as fermented foods, meat, and the human gastrointestinal tract, exhibits significant genetic diversity and niche-specific adaptations. This study conducts a comprehensive comparative genomic analysis of 30 complete L. sakei genomes to uncover the genetic mechanisms underlying these adaptations. Phylogenetic analysis divided the species into three distinct clades that did not correlate with the source of isolation and did not suggest any niche-specific evolutionary direction. The pan-genome analysis revealed a substantial core genome alongside a diverse genetic repertoire, indicating both high genetic conservation and adaptability. Predicted growth rates based on codon use bias analysis suggest that L. sakei strains have an overall faster growth rate and may be able to efficiently dominant in competitive environments. Plasmid analysis revealed a variety of plasmids carrying genes essential for carbohydrate metabolism, enhancing L. sakei’s ability to thrive in various fermentation substrates. It was also found that the number of genes belonging to the GH1 family among sugar metabolism-related genes present on chromosomes and plasmids varies between strains, and that AA1, which is involved in alcohol oxidation, has been acquired from plasmids. BLAST analysis revealed that some strains have environmental adaptation gene clusters of cell surface polysaccharides that may mediate attachment to food and mucosa. These findings not only underscore the genetic and functional diversity of L. sakei but also highlight its potential as a potent starter culture in fermentation and as a probiotic. The knowledge gleaned from this study lays a solid foundation for future research aimed at harnessing the genetic traits of L. sakei strains for industrial and health-related applications.","PeriodicalId":9124,"journal":{"name":"bioRxiv","volume":"5 11","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141642200","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}
bioRxivPub Date : 2024-07-16DOI: 10.1101/2024.07.11.603062
Yan Zhao, Hanshuo Zhu, Jinqian Li, Li Sun
{"title":"T3SS translocon induces pyroptosis by direct interaction with NLRC4/NAIP inflammasome","authors":"Yan Zhao, Hanshuo Zhu, Jinqian Li, Li Sun","doi":"10.1101/2024.07.11.603062","DOIUrl":"https://doi.org/10.1101/2024.07.11.603062","url":null,"abstract":"Type III secretion system (T3SS) is a virulence apparatus existing in many bacterial pathogens. Structurally, T3SS consists of the base, needle, tip, and translocon. The NLRC4 inflammasome is the major receptor for T3SS needle and basal rod proteins. Whether other T3SS components are recognized by NLRC4 is unclear. In this study, using Edwardsiella tarda as a model intracellular pathogen, we examined T3SS−inflammasome interaction and its effect on cell death. E. tarda induced pyroptosis in a manner that required the bacterial translocon and the host inflammasome proteins of NLRC4, NLRP3, ASC, and caspase 1/4. The translocon protein EseB triggered NLRC4/NAIP-mediated pyroptosis by binding NAIP via its C-terminal region, particularly the terminal 6 residues (T6R). EseB homologs exist widely in T3SS-positive bacteria and share high identities in T6R. Like E. tarda EseB, all of the representatives of the EseB homologs exhibited T6R-dependent NLRC4 activation ability. Together these results revealed the function and molecular mechanism of EseB to induce host cell pyroptosis and suggested a highly conserved inflammasome-activation mechanism of T3SS translocon in bacterial pathogens.","PeriodicalId":9124,"journal":{"name":"bioRxiv","volume":"21 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141644188","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}
bioRxivPub Date : 2024-07-16DOI: 10.1101/2024.07.10.602558
Art Riddle, Taasin Srivastava, Kang Wang, Eduardo Tellez, Hanna O’Neill, Xi Gong, Abigail O'Niel, Jaden A Bell, Jacob Raber, Matthew Lattal, James Maylie, Stephen A. Back
{"title":"Mild neonatal hypoxia disrupts adult hippocampal learning and memory and is associated with CK2-mediated dysregulation of synaptic calcium-activated potassium channel KCNN2","authors":"Art Riddle, Taasin Srivastava, Kang Wang, Eduardo Tellez, Hanna O’Neill, Xi Gong, Abigail O'Niel, Jaden A Bell, Jacob Raber, Matthew Lattal, James Maylie, Stephen A. Back","doi":"10.1101/2024.07.10.602558","DOIUrl":"https://doi.org/10.1101/2024.07.10.602558","url":null,"abstract":"Objective Although nearly half of preterm survivors display persistent neurobehavioral dysfunction including memory impairment without overt gray matter injury, the underlying mechanisms of neuronal or glial dysfunction, and their relationship to commonly observed cerebral white matter injury are unclear. We developed a mouse model to test the hypothesis that mild hypoxia during preterm equivalence is sufficient to persistently disrupt hippocampal neuronal maturation related to adult cellular mechanisms of learning and memory. Methods: Neonatal (P2) mice were exposed to mild hypoxia (8%O2) for 30 min and evaluated for acute injury responses or survived until adulthood for assessment of learning and memory and hippocampal neurodevelopment. Results Neonatal mild hypoxia resulted in clinically relevant oxygen desaturation and tachycardia without bradycardia and was not accompanied by cerebral gray or white matter injury. Neonatal hypoxia exposure was sufficient to cause hippocampal learning and memory deficits and abnormal maturation of CA1 neurons that persisted into adulthood. This was accompanied by reduced hippocampal CA3-CA1 synaptic strength and LTP and reduced synaptic activity of calcium-sensitive SK2 channels, key regulators of spike timing dependent neuroplasticity, including LTP. Structural illumination microscopy revealed reduced synaptic density, but intact SK2 localization at the synapse. Persistent loss of SK2 activity was mediated by altered casein kinase 2 (CK2) signaling. Interpretation Clinically relevant mild hypoxic exposure in the neonatal mouse is sufficient to produce morphometric and functional disturbances in hippocampal neuronal maturation independently of white matter injury. Additionally, we describe a novel persistent mechanism of potassium channel dysregulation after neonatal hypoxia. Collectively our findings suggest an unexplored explanation for the broad spectrum of neurobehavioral, cognitive and learning disabilities that paradoxically persist into adulthood without overt gray matter injury after preterm birth.","PeriodicalId":9124,"journal":{"name":"bioRxiv","volume":"91 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141642718","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}
bioRxivPub Date : 2024-07-16DOI: 10.1101/2024.07.11.603013
Noam Saadon-Grosman, Tsahi Asher, Y. Loewenstein
{"title":"On the Geometry of Somatosensory Representations in the Cortex","authors":"Noam Saadon-Grosman, Tsahi Asher, Y. Loewenstein","doi":"10.1101/2024.07.11.603013","DOIUrl":"https://doi.org/10.1101/2024.07.11.603013","url":null,"abstract":"It is well-known that cortical areas specializing in the processing of somatosensory information from different parts of the body are arranged in an orderly manner along the cortex. It is also generally accepted that in the cortex, somatosensory information is initially processed in the primary somatosensory cortex and from there, it is hierarchically processed in other cortical regions. Previous studies have focused on the organization of representation at a level of a single or few cortical regions, identifying multiple body maps. However, the question of the large-scale organization of these different maps, and their relation to the hierarchical organization has received little attention. This is primarily because the highly convoluted shape of the cortical surface makes it difficult to characterize the relationship between cortical areas that are centimeters apart. Here, we used functional MRI to characterize cortical responses to full-body light touch stimulation. Our results indicate that the organization of both body representation and hierarchy is radial, with a small number of extrema that reign over a large number of cortical regions. Quantitatively computing the local relationship between the gradients of body and hierarchy maps, we show that the interaction between these two radial geometries, body representation and hierarchy in S1 are approximately orthogonal. However, this orthogonality is restricted to S1. Similar organizational patterns in the visual and auditory systems suggest that radial topography may be a common feature across sensory systems. Significance statement The sensation of touch on our skin is represented in the brain as a map, where body parts are organized sequentially from head to toe. In the cerebral cortex, multiple body maps are distributed across numerous regions, processing signals at different hierarchical levels. Is there a large-scale organization of these body maps in the cerebral cortex? We show that all previously known body maps and their hierarchies are organized with a radial geometry. Similar radial geometry may also characterize the visual and auditory systems, indicating that radial geometry is a common organizational principle of sensory processing in the cortex.","PeriodicalId":9124,"journal":{"name":"bioRxiv","volume":"87 15","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141642728","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}
bioRxivPub Date : 2024-07-16DOI: 10.1101/2024.07.12.603135
A. García Jiménez, T. Gaboriau, L. M. Fitzgerald, Sara Heim, A. Marcionetti, S. Schmid, Joris A. M. Bertrand, G. Litsios, Abigail Shaughnessy, Carl Santiago, Ploypallin Rangseethampanya, Phurinat Ruttanachuchote, Wiphawan Aunkhongthong, Sittiporn Pengsakun, M. Sutthacheep, B. Frédérich, Fabio Cortesi, Thamasak Yemin, N. Salamin
{"title":"Specialization into Host Sea Anemones Impacted Clownfish Demographic Responses to Pleistocene Sea Level Changes","authors":"A. García Jiménez, T. Gaboriau, L. M. Fitzgerald, Sara Heim, A. Marcionetti, S. Schmid, Joris A. M. Bertrand, G. Litsios, Abigail Shaughnessy, Carl Santiago, Ploypallin Rangseethampanya, Phurinat Ruttanachuchote, Wiphawan Aunkhongthong, Sittiporn Pengsakun, M. Sutthacheep, B. Frédérich, Fabio Cortesi, Thamasak Yemin, N. Salamin","doi":"10.1101/2024.07.12.603135","DOIUrl":"https://doi.org/10.1101/2024.07.12.603135","url":null,"abstract":"Fluctuating sea levels during the Pleistocene led to habitat loss and fragmentation, impacting the evolutionary trajectories of reef fishes. Species with specialized ecological requirements or habitat preferences, like clownfishes (Amphiprioninae), may have been particularly vulnerable due to their intricate dependence on sea anemones. The diverse host specializations within this group likely contributed distinct responses to sea-level fluctuations, differentially shaping their recent evolutionary histories. Leveraging a comprehensive genomic dataset, we reveal demographic patterns and connectivity dynamics across multiple populations of ten clownfish species under different host specializations. Host-generalist species demonstrated strong resilience to habitat perturbations, while those specialized on single hosts suffered dramatic bottlenecks linked to sea-level fluctuations. Spatial analyses revealed the significant role of oceanic currents in shaping clownfish genetic diversity landscapes. Dispersal barriers were driven by environmental variables, with the Coral Triangle emerging as a hub of genetic diversity. Our results reveal how clownfish associative behavior influences their population dynamics, holding major implications for their conservation such as the need to consider their mutualism with sea anemones, particularly on host-specialists, to ensure their survival in the face of climate threats. These findings extend broader principles of conservation, improving our understanding of species’ responses to ecological constraints and environmental changes over evolutionary timescales.","PeriodicalId":9124,"journal":{"name":"bioRxiv","volume":"25 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141644146","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}
bioRxivPub Date : 2024-07-16DOI: 10.1101/2024.07.15.603602
Anusha D. Bhatt, Madeleine G. Brown, Aurora B. Wackford, Yuki Shindo, Amanda A. Amodeo
{"title":"Local nuclear to cytoplasmic ratio regulates chaperone-dependent H3 variant incorporation during zygotic genome activation","authors":"Anusha D. Bhatt, Madeleine G. Brown, Aurora B. Wackford, Yuki Shindo, Amanda A. Amodeo","doi":"10.1101/2024.07.15.603602","DOIUrl":"https://doi.org/10.1101/2024.07.15.603602","url":null,"abstract":"Early embryos often have relatively unstructured chromatin that lacks active and inactive domains typical of differentiated cells. In many species, these regulatory domains are established during zygotic genome activation (ZGA). In Drosophila, ZGA occurs after 13 fast, reductive, syncytial nuclear divisions during which the nuclear to cytoplasmic (N/C) ratio grows exponentially. These divisions incorporate maternally-loaded, cytoplasmic pools of histones into chromatin. Previous work found that chromatin incorporation of replication-coupled histone H3 decreases while its variant H3.3 increases in the cell cycles leading up to ZGA. In other cell types, H3.3 is associated with sites of active transcription as well as heterochromatin, suggesting a link between H3.3 incorporation and ZGA. Here, we examine the factors that contribute to H3.3 incorporation at ZGA. We identify a more rapid decrease in the nuclear availability of H3 than H3.3 over the final pre-ZGA cycles. We also observe an N/C ratio-dependent increase in H3.3 incorporation in mutant embryos with non-uniform local N/C ratios. We find that chaperone binding, not gene expression, controls incorporation patterns using H3/H3.3 chimeric proteins at the endogenous H3.3A locus. We test the specificity of the H3.3 chaperone pathways for H3.3 incorporation using Hira (H3.3 chaperone) mutant embryos. Overall, we propose a model in which local N/C ratios and specific chaperone binding regulate differential incorporation of H3.3 during ZGA. Graphical abstract","PeriodicalId":9124,"journal":{"name":"bioRxiv","volume":"5 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141641075","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}
bioRxivPub Date : 2024-07-16DOI: 10.1101/2024.07.12.603194
Zhifei Wu, Baoshan Liao, Julia Ying, Jan Keung, Zongli Zheng, Virpi Ahola, Wenjun Xiong
{"title":"Müller glia cell cycle re-activation by simultaneous cyclin D1 overexpression and p27kip1 knockdown promotes retinal regeneration in mice","authors":"Zhifei Wu, Baoshan Liao, Julia Ying, Jan Keung, Zongli Zheng, Virpi Ahola, Wenjun Xiong","doi":"10.1101/2024.07.12.603194","DOIUrl":"https://doi.org/10.1101/2024.07.12.603194","url":null,"abstract":"Harnessing the regenerative potential of endogenous stem cells to restore lost neurons is a promising strategy for treating neurodegenerative disorders. Müller glia (MG), the primary glial cell type in the retina, exhibit remarkable regenerative abilities in lower vertebrate species, such as zebrafish and amphibians, where injury induces MG to proliferate and differentiate into various retinal neuron types. The regenerative potential of mammalian MG is constrained by their inherent inability to re-enter the cell cycle, likely due to high levels of the cell cycle inhibitor p27Kip1 and low levels of cyclin D1 observed in adult mouse MG. In this study, we found that adeno-associated virus (AAV)-mediated cyclin D1 overexpression and p27Kip1 knockdown exerts a strong synergistic effect on MG proliferation. MG proliferation induced by this treatment was potent but self-limiting, as MG did not undergo uncontrolled proliferation or lead to retinal neoplasia. Single-cell RNA sequencing (scRNA-seq) revealed that cell cycle reactivation leads to immunosuppression and dedifferentiation of MG. Notably, scRNA-seq analysis identified a new cluster of rod-like MG cells expressing both rod and MG genes, which was further validated by RNA in situ hybridization. Cell cycle reactivation also led to de novo genesis of bipolar- and amacrine-like cells from MG. Overall, our findings suggest that AAV- mediated cyclin D1 overexpression and p27Kip1 knockdown stimulate MG proliferation and promote MG reprogramming. This approach may be a promising strategy, especially when combined with other regeneration-promoting factors, to enhance MG-mediated retinal repair.","PeriodicalId":9124,"journal":{"name":"bioRxiv","volume":"11 5","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141640546","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}
bioRxivPub Date : 2024-07-16DOI: 10.1101/2024.07.15.603480
Kejia Wu, Hanlun Jiang, Derrick R. Hicks, Caixuan Liu, Edin Muratspahić, T. A. Ramelot, Yuexuan Liu, Kerrie E. McNally, Amit Gaur, B. Coventry, Wei Chen, Asim K. Bera, A. Kang, Stacey R Gerben, Mila Lamb, Analisa Murray, Xinting Li, Madison A. Kennedy, Wei Yang, Gudrun Schober, Stuart M. Brierley, Michael H. Gelb, Gaetano T. Montelione, Emmanuel Derivery, David Baker
{"title":"Sequence-specific targeting of intrinsically disordered protein regions","authors":"Kejia Wu, Hanlun Jiang, Derrick R. Hicks, Caixuan Liu, Edin Muratspahić, T. A. Ramelot, Yuexuan Liu, Kerrie E. McNally, Amit Gaur, B. Coventry, Wei Chen, Asim K. Bera, A. Kang, Stacey R Gerben, Mila Lamb, Analisa Murray, Xinting Li, Madison A. Kennedy, Wei Yang, Gudrun Schober, Stuart M. Brierley, Michael H. Gelb, Gaetano T. Montelione, Emmanuel Derivery, David Baker","doi":"10.1101/2024.07.15.603480","DOIUrl":"https://doi.org/10.1101/2024.07.15.603480","url":null,"abstract":"A general approach to design proteins that bind tightly and specifically to intrinsically disordered regions (IDRs) of proteins and flexible peptides would have wide application in biological research, therapeutics, and diagnosis. However, the lack of defined structures and the high variability in sequence and conformational preferences has complicated such efforts. We sought to develop a method combining biophysical principles with deep learning to readily generate binders for any disordered sequence. Instead of assuming a fixed regular structure for the target, general recognition is achieved by threading the query sequence through diverse extended binding modes in hundreds of templates with varying pocket depths and spacings, followed by RFdiffusion refinement to optimize the binder-target fit. We tested the method by designing binders to 39 highly diverse unstructured targets. Experimental testing of ∼36 designs per target yielded binders with affinities better than 100 nM in 34 cases, and in the pM range in four cases. The co-crystal structure of a designed binder in complex with dynorphin A is closely consistent with the design model. All by all binding experiments for 20 designs binding diverse targets show they are highly specific for the intended targets, with no crosstalk even for the closely related dynorphin A and dynorphin B. Our approach thus could provide a general solution to the intrinsically disordered protein and peptide recognition problem.","PeriodicalId":9124,"journal":{"name":"bioRxiv","volume":"7 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141642787","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}
bioRxivPub Date : 2024-07-16DOI: 10.1101/2024.07.10.602916
Avery Hinks, Ethan Vlemmix, Geoffrey A. Power
{"title":"Submaximal eccentric resistance training increases serial sarcomere number and improves dynamic muscle performance in old rats","authors":"Avery Hinks, Ethan Vlemmix, Geoffrey A. Power","doi":"10.1101/2024.07.10.602916","DOIUrl":"https://doi.org/10.1101/2024.07.10.602916","url":null,"abstract":"The age-related loss of muscle mass is partly accounted for by the loss of sarcomeres in series. Serial sarcomere number (SSN) influences muscle mechanical function including the force-length and force-velocity-power relationships, and the age-related loss of SSN contributes to declining performance. Resistance training biased to active lengthening (eccentric) contractions increases SSN in young muscle, however, we showed maximal eccentric training in old rats did not alter SSN and further worsened performance. A submaximal eccentric training stimulus may be more conducive to adaptation for aged muscle. Therefore, the purpose of this study was to assess whether submaximal eccentric training can increase SSN and improve mechanical function in old rats. Twelve 32-month-old male F344/BN rats completed 4 weeks of submaximal (60% maximum) isokinetic eccentric plantar-flexion training 3 days/week. Pre- and post-training, we assessed in-vivo maximum isometric torque at a stretched and neutral ankle angle, the passive torque-angle relationship, and the isotonic torque-angular velocity-power relationship. The soleus and MG were harvested for SSN measurements via laser diffraction, with the untrained leg as a control. SSN increased 11% and 8%, and muscle wet weight increased 14% and 13% in the soleus and MG, respectively. Maximum isometric torque and shortening velocity were unaltered, but there was a shift towards longer muscle lengths for the optimal angle of torque production, a 42% reduction of passive torque, and 23% increase in peak isotonic power. Eccentric training at 60% maximum was beneficial for aged muscle, increasing SSN and muscle mass, reducing muscle passive tension, and improving dynamic performance. New & Noteworthy Four weeks of submaximal (60% of maximum) eccentric resistance training increased serial sarcomere number and muscle mass in old rats Increased serial sarcomere number corresponded to broadening of the torque-angle relationship following training, which contributed to increased peak isotonic power Submaximal eccentric training also led to a large reduction in passive torque throughout the range of motion","PeriodicalId":9124,"journal":{"name":"bioRxiv","volume":"31 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141643860","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}
bioRxivPub Date : 2024-07-16DOI: 10.1101/2024.07.12.603291
Ryan Pellow, J. M. Comeron
{"title":"A wavelet-based approach generates quantitative, scale-free and hierarchical descriptions of 3D genome structures and new biological insights","authors":"Ryan Pellow, J. M. Comeron","doi":"10.1101/2024.07.12.603291","DOIUrl":"https://doi.org/10.1101/2024.07.12.603291","url":null,"abstract":"Eukaryotes fold their genomes within nuclei in three-dimensional space, with coordinated multiscale structures including loops, topologically associating domains (TADs), and higher-order chromosome territories. This 3D organization plays essential roles in gene regulation and development, responses to physiological stress, and disease. However, current methodologies to infer these 3D structures from genomic data have limitations. These include varying outcomes depending on the resolution of the analysis and sequencing depth, qualitative results that hinder statistical comparisons, lack of insight into the frequency of the structures in samples with many genomes, and no direct inference of hierarchical structures. These shortcomings can make it difficult for the rigorous comparison of 3D properties across genomes, between experimental conditions, or species. To address these challenges, we developed a wavelet transform-based method (WaveTAD) that describes the 3D nuclear organization in a resolution-free, probabilistic, and hierarchical manner. WaveTAD generates probabilities that capture the variable frequency within samples and shows increased accuracy and sensitivity compared to current approaches. We applied WaveTAD to multiple datasets from Drosophila, mouse, and humans to illustrate new biological insights that our more sensitive and quantitative approach provides, such as the widespread presence of embryonic 3D organization before zygotic genome activation, the effect of multiple CTCF units on the stability of loops and TADs, and the association between gene expression and TAD structures in COVID-19 patients or sex-specific transcription in Drosophila.","PeriodicalId":9124,"journal":{"name":"bioRxiv","volume":"13 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141643928","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}