bioRxiv最新文献

{"title":"The open to closed D-loop conformational switch determines length in filopodia-like actin bundles","authors":"Jonathan R. Gadsby, P. S. Ioannou, Richard Butler, Julia Mason, Alison Smith, U. Dobramysl, Stacey Chin, Claire L. Dobson, J. Gallop","doi":"10.1101/2024.08.09.607305","DOIUrl":"https://doi.org/10.1101/2024.08.09.607305","url":null,"abstract":"Filopodia, microspikes and cytonemes are implicated in sensing the environment and in dissemination of morphogens, organelles and pathogens across tissues. Their major structural component is parallel bundles of actin filaments that assemble from the cell membrane. Whilst the length of filopodia is central to their function, it is not known how their lengths are determined by actin bundle dynamics. Here, we identified a set of monoclonal antibodies that lengthen filopodia-like structures formed in a cell-free reconstitution system, and used them to uncover a key molecular switch governing length regulation. Using immunolabelling, enzyme-linked immunosorbent assays, immunoprecipitation and immunoblock experiments, we identified four antibodies that lengthen actin bundles by selectively binding the open DNase 1-binding loop (D-loop) of actin filaments. The antibodies inhibit actin disassembly and their effects can be alleviated by providing additional actin or cofilin. This work indicates that maintaining an open state of the actin filament D-loop is a mechanism of generating the long projections of filopodia-like actin bundles.","PeriodicalId":505198,"journal":{"name":"bioRxiv","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141924500","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":"PTEN neddylation aggravates CDK4/6 inhibitor resistance in breast cancer","authors":"Fan Liu, Weixiao Liu, Yawen Tan, Yaxin Shang, Sihui Ling, Xiaokun Jiang, Zhen Zhang, Shiyao Sun, Ping Xie","doi":"10.1101/2024.08.06.606911","DOIUrl":"https://doi.org/10.1101/2024.08.06.606911","url":null,"abstract":"The gradual emergence of a novel therapeutic approach lies in the restoration of tumor suppressive machinery, specifically targeting PTEN. Protein neddylation modification contributes to PTEN inactivation and fuels breast cancer progression. Here, we highlight elevated level of PTEN neddylation is markedly associated with resistance against Palbociclib, a CDK4/6 inhibitor used in HR+/HER2-breast cancer patients. Strikingly, we identified a potent inhibitor of PTEN neddylation which could obviously re-sensitized Palbociclib-therapy-resistant breast cancer. Mechanistically, PTEN neddylation activates the PI3K/Akt signaling pathway, and more importantly, it stabilizes JUND by disrupting the interplay with its E3 ubiquitin ligase, ITCH. Therefore, the enhanced stability of JUND activates the AP-1/MAPK signaling pathway, resulting in the release of cytokines and chemokines, in turn, reprograming the tumor microenvironment, contributing to drug resistance, tumor recurrence and metastasis. This novel insight underscores the potential of targeting PTEN neddylation as a promising strategy for restoring the activity of key tumor suppressor and overcoming resistance in breast cancer therapy.","PeriodicalId":505198,"journal":{"name":"bioRxiv","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141921733","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":"Renal cancer cells acquire immune surface protein through trogocytosis and horizontal gene transfer","authors":"Haley Q. Marcarian, Anutr Sivakoses, Anika M. Arias, Olivia C. Ihedioha, Benjamin R. Lee, Maria C. Bishop, Alfred L.M. Bothwell","doi":"10.1101/2024.08.07.607036","DOIUrl":"https://doi.org/10.1101/2024.08.07.607036","url":null,"abstract":"Trogocytosis is an underappreciated phenomenon that shapes the immune microenvironment surrounding many types of solid tumors. The consequences of membrane-bound proteins being deposited from a donor immune cell to a recipient cancer cell via trogocytosis are still unclear. Here, we report that human clear cell renal carcinoma tumors stably express the lymphoid markers CD45, CD56, CD14, and CD16. Flow cytometry performed on fresh kidney tumors revealed consistent CD45 expression on tumor cells, as well as varying levels of the other markers mentioned previously. These results were consistent with our immunofluorescent analysis, which also revealed colocalization of lymphoid markers with carbonic anhydrase 9 (CAIX), a standard kidney tumor marker. RNA analysis showed a significant upregulation of genes typically associated with immune cells in tumor cells following trogocytosis. Finally, we show evidence of chromosomal DNA being transferred from immune cells to tumor cells during trogocytosis. This horizontal gene transfer has transcriptional consequences in the recipient tumor cell, resulting in a fusion phenotype that expressed both immune and cancer specific proteins. This work demonstrates a novel mechanism by which tumor cell protein expression is altered through the acquisition of surface membrane fragments and genomic DNA from infiltrating lymphocytes. These results alter the way in which we understand tumor-immune cell interactions and may reveal new insights into the mechanisms by which tumors develop. Additionally, further studies into trogocytosis will help push the field towards the next generation of immunotherapies and biomarkers for treating renal cell carcinoma and other types of cancers. SIGNIFICANCE STATEMENT We have identified trogocytosis as a mechanism by which human clear cell renal carcinoma tumors acquire lymphocyte surface protein expression from tumor infiltrating immune cells. In addition to the transfer of membrane fragments, we have provided evidence to show that genomic DNA is transferred from a normal immune cell to a tumor cell during trogocytosis. This process alters the transcriptome of cancer cells such that they express significantly more mRNA for immune proteins such as the lymphocyte marker CD45 compared to tumor cells that have not undergone trogocytosis. This study provides an in-depth analysis of the interactions between cancer cells and tumor infiltrating lymphocytes, and how these interactions alter the development of human tumors.","PeriodicalId":505198,"journal":{"name":"bioRxiv","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141923095","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":"Cellular context specific tuning of actomyosin ring contractility within a common cytoplasm","authors":"John B. Linehan, Alexandra Zampetaki, Michael E. Werner, Bryan W. Heck, Paul S. Maddox, Sebastian Fürthauer, A. S. Maddox","doi":"10.1101/2024.08.08.607200","DOIUrl":"https://doi.org/10.1101/2024.08.08.607200","url":null,"abstract":"The non-muscle actomyosin cytoskeleton generates contractile force through the dynamic rearrangement of its constituent parts. Actomyosin rings are a specialization of the non-muscle actomyosin cytoskeleton that are associated with a number of cell biological processes. To explore how contractile forces are generated by actomyosin rings, we studied three instances of ring closure within the common cytoplasm of the C. elegans oogenic germline: when germline stem cells (GSCs) divide mitotically, when meiotic compartments undergo apoptosis, and when nascent oocytes cellularize. We found that each of these rings closed with unique kinetics, protein density and abundance dynamics. These measurements suggested that the mechanism of contractile force generation varied across the subcellular contexts. Next, we formulated a physical model that related the forces generated by filament-filament interactions to the material properties of these rings that dictate the kinetics of their closure. Using this framework, we related the density of conserved cytoskeletal proteins anillin and myosin to the kinematics of ring closure. We found that actomyosin ring closure results from the asymmetric distribution of protein along the length of F-actin, which occurs naturally due to differences in crosslinker and NMMII bundle size. Our work predicts that the role of myosin varies across these ring types, due in part to its distribution along F-actin and motoring.","PeriodicalId":505198,"journal":{"name":"bioRxiv","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141923210","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":"All-Diamond Boron-Doped Microelectrodes for Neurochemical Sensing with Fast-Scan Cyclic Voltammetry","authors":"Bhavna Gupta, Brandon Kepros, Jann B. Landgraf, Michael F. Becker, Wen Li, Erin K. Purcell, James R. Siegenthaler","doi":"10.1101/2024.08.07.606919","DOIUrl":"https://doi.org/10.1101/2024.08.07.606919","url":null,"abstract":"Neurochemical sensing with implantable devices has gained remarkable attention over the last few decades. A promising area of this research is the progress of novel electrodes as electrochemical tools for neurotransmitter detection in the brain. The boron-doped diamond (BDD) electrode is one such candidate that previously has been reported for its excellent electrochemical properties, including a wide working potential, superior chemical inertness and mechanical stability, good biocompatibility and resistance to fouling. Meanwhile, limited research has been conducted on the BDD as a microelectrode for neurochemical detection. Our team has developed a freestanding, all diamond microelectrode consisting of a boron-doped polycrystalline diamond core, encapsulated in an insulating polycrystalline diamond shell, with a cleaved planar tip for electrochemical sensing. This all-diamond electrode is advantageous due to its – (1) batch fabrication using wafer technology that eliminates traditional hand fabrication errors and inconsistencies, (2) absence of metal-based wires, or foundations, to improve biocompatibility and flexibility, and (3) sp3 carbon surface with resistance to biofouling, i.e. adsorption of proteins or unwanted molecules at the electrode surface in a biological environment that impedes overall electrode performance. Here, we provide findings on further in vitro testing and development of the freestanding boron-doped diamond microelectrode (BDDME) for neurotransmitter detection using fast scan cyclic voltammetry (FSCV). In this report, we elaborate on – 1) an updated fabrication scheme and work flow to generate all diamond BDDMEs, 2) slow scan cyclic voltammetry measurements of reference and target analytes to understand basic electrochemical behavior of the electrode, and 3) FSCV characterization of common neurotransmitters, and overall favorability of serotonin (5-HT) detection. The BDDME showed a 2-fold increased FSCV response for 5-HT in comparison to dopamine (DA), with a limit of detection of 0.16 µM for 5-HT and 0.26 µM for DA. These results are intended to expand on the development of the next generation BDDME and guide future in vivo experiments, adding to the growing body of literature on implantable devices for neurochemical sensing.","PeriodicalId":505198,"journal":{"name":"bioRxiv","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141924187","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 effect of performance contingent reward prospects flexibly adapts to more versus less specific task goals","authors":"Nathalie Liegel, Daniel Schneider, Edmund Wascher, Laura-Isabelle Klatt, Stefan Arnau","doi":"10.1101/2024.08.07.607018","DOIUrl":"https://doi.org/10.1101/2024.08.07.607018","url":null,"abstract":"In some situations, e.g., when we expect to gain a reward in case of good performance, goal-driven top-down attention is particularly strong. Little is known about the task specificity of such increases of top-down attention due to environmental factors. To understand to what extent performance-contingent reward prospects can result in specific and unspecific changes in cognitive processing, we here investigate reward effects under different levels of task specification. Thirty-two participants performed a visual or an auditory discrimination task cued by two consecutive visual stimuli: First, a reward cue indicated if good performance was rewarded. Second, a task cue announced either which of the two tasks would follow (precise cue) or that both tasks would follow equally likely (imprecise cue). Reward and task cue preciseness both significantly improved performance. Moreover, the response time difference between precisely and imprecisely cued trials was significantly stronger in rewarded than in unrewarded trials. These effects were reflected in ERP slow wave amplitudes: Reward and preciseness both significantly enhanced the contingent negative variation (CNV) prior to the task stimulus. In an early CNV time interval, both factors also showed an interaction. A negative slow wave prior to the task cue was also significantly enhanced for rewarded trials. This effect correlated with the reward difference in response times. These results indicate that reward prospects trigger task-specific changes in preparatory top-down attention which can flexibly adapt over time and across different task requirements. This highlights that a reward-induced increase of cognitive control can occur on different specificity levels.","PeriodicalId":505198,"journal":{"name":"bioRxiv","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141924505","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":"Expanding kinetoplastid genome annotation through protein structure comparison","authors":"J.M. Trinidad-Barnech, J.R. José Sotelo-Silveira, D. Fernandez Do Porto, P. Smircich","doi":"10.1101/2024.08.07.607044","DOIUrl":"https://doi.org/10.1101/2024.08.07.607044","url":null,"abstract":"Kinetoplastids belong to the supergroup Discobids, an early divergent eukaryotic clade. Although the amount of genomic information on these parasites has grown substantially, assigning gene functions through traditional sequence-based homology methods remains challenging. Recently, significant advancements have been made in in silico protein structure prediction and algorithms for rapid and precise large-scale protein structure comparisons. In this work, we developed a protein structure-based homology search pipeline (ASC, Annotation by Structural Comparisons) and applied it to annotate all kinetoplastid proteins available in TriTrypDB. Our pipeline assigned functional annotation to 23,000 hypothetical proteins across all 35 kinetoplastid species in the database. Among these, we identified ubiquitous eukaryotic proteins that had not been previously detected in kinetoplastid genomes. The resulting annotations (KASC, Kinetoplastid Annotation by Structural Comparison) are openly available to the community (kasc.fcien.edu.uy). Author Summary Kinetoplastids are a group of parasites that cause severe diseases in the poorest regions of the world. Despite the increasing amount of genomic information available on these parasites, predicting the function of many of their genes using traditional methods has been difficult. Recently, there have been significant advancements in predicting protein structures and comparing them on a large scale. In this study, we created a new method called ASC (Annotation by Structural Comparisons) to find functions for all the kinetoplastid genes listed in the TriTrypDB database. Our strategy successfully assigned functions to 23,000 proteins in kinetoplastids. Among these, we discovered important proteins found in all eukaryotes that had not been previously identified in kinetoplastids. This information (KASC, Kinetoplastid Annotation by Structural Comparison) is freely available at kasc.fcien.edu.uy.","PeriodicalId":505198,"journal":{"name":"bioRxiv","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141923243","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":"HCM-associated mutations in MYH6/7 drive pathologic expression of TGF-β1 in cardiomyocytes within weeks of developmental specification","authors":"Jeanne Hsieh, Megan A. L. Hall, Mohammad Shameem, Patrick J. Ernst, Forum Kamdar, Bhairab N. Singh, Robert L. Meisel, Brenda M. Ogle","doi":"10.1101/2024.08.08.606705","DOIUrl":"https://doi.org/10.1101/2024.08.08.606705","url":null,"abstract":"Hypertrophic cardiomyopathy (HCM) is characterized by myocyte hypertrophy, sarcomere disarray, and myocardial fibrosis, leading to significant morbidity and mortality. As the most common inherited cardiomyopathy, HCM largely results from mutations in sarcomeric protein genes. Current treatments for HCM primarily focus on alleviating late-stage symptoms, with a critical gap in the detailed understanding of early-stage deficiencies that drive disease progression. We recently showed, in monolayers of cardiomyocytes derived from human induced pluripotent stem cells (hiPSCs) with MYH7 R723C and MYH6 R725C mutations, altered expression of several extracellular matrix (ECM)-related genes with associated defects in cardiomyocyte-ECM adhesion. To better evaluate the cardiomyocyte-ECM interface and pathological ECM dynamics in early-stage HCM, here we adopted a 3D engineered heart tissue (EHT) model containing both cardiomyocytes and fibroblasts, the primary contributor to ECM remodeling. Mutant EHTs showed aberrant cardiomyocyte distribution, augmented calcium handling, and force generation compared to controls. Altered proteoglycan deposition and increased phosphorylated focal adhesion kinase (pFAK) further indicated changes in ECM composition and connectivity. Elevated transforming growth factor beta-1 (TGF-β1) secretion and a higher proportion of activated fibroblasts were identified in mutant EHTs, along with sustained TGF-β1 transcription specifically in mutant cardiomyocytes. Remarkably, blocking TGF-β1 receptor signaling reduced fibroblast activation and contraction force to control levels. This study underscores the early interplay of mutant hiPSC-CMs with fibroblasts, wherein mutant cardiomyocytes initiate fibroblast activation via TGF-β1 overexpression, independent of the immune system. These findings provide a promising foundation for developing and implementing novel strategies to treat HCM well before the manifestation of clinically detectable fibrosis and cardiac dysfunction.","PeriodicalId":505198,"journal":{"name":"bioRxiv","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141923890","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":"Msh2-Msh3 DNA-binding is not sufficient to promote trinucleotide repeat expansions in Saccharomyces cerevisiae","authors":"Katherine M. Casazza, Gregory M. Williams, Lauren Johengen, Gavin Twoey, J. Surtees","doi":"10.1101/2024.08.08.607243","DOIUrl":"https://doi.org/10.1101/2024.08.08.607243","url":null,"abstract":"Mismatch repair (MMR) is a highly conserved DNA repair pathway that recognizes mispairs that occur spontaneously during DNA replication and coordinates their repair. In Saccharomyces cerevisiae, Msh2-Msh3 and Msh2-Msh6 initiate MMR by recognizing and binding insertion deletion loops (in/dels) up to ∼ 17 nucleotides (nt.) and base-base mispairs, respectively; the two complexes have overlapping specificity for small (1-2 nt.) in/dels. The DNA-binding specificity for the two complexes resides in their respective mispair binding domains (MBDs) and have distinct DNA-binding modes. Msh2-Msh3 also plays a role in promoting CAG/CTG trinucleotide repeat (TNR) expansions, which underlie many neurodegenerative diseases such as Huntington’s Disease and Myotonic Dystrophy Type 1. Models for Msh2-Msh3’s role in promoting TNR tracts expansion have invoked its specific DNA-binding activity and predict that the TNR structure alters its DNA binding and downstream activities to block repair. Using a chimeric Msh complex that replaces the MBD of Msh6 with the Msh3 MBD, we demonstrate that Msh2-Msh3 DNA-binding activity is not sufficient to promote TNR expansions. We propose a model for Msh2-Msh3-mediated TNR expansions that requires a fully functional Msh2-Msh3 including DNA binding, coordinated ATP binding and hydrolysis activities and interactions with Mlh complexes that are analogous to those required for MMR. Article Summary The mismatch repair (MMR) protein complex Msh2-Msh3 promotes trinucleotide repeat (TNR) expansions that can lead to neurodegenerative diseases, while the Msh2-Msh6 complex does not. We tested the hypothesis that Msh2-Msh3’s specific DNA binding activity is sufficient to promote TNR expansions, using a chimeric MSH complex in vivo and in vitro. We found that the Msh2-Msh3-like DNA-binding was not sufficient to promote TNR expansions. Our findings indicate that Msh2-Msh3 plays an active, pathogenic role in promoting TNR expansions beyond simply binding to TNR structures.","PeriodicalId":505198,"journal":{"name":"bioRxiv","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141922521","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":"UltraTimTrack: a Kalman-filter-based algorithm to track muscle fascicles in ultrasound image sequences","authors":"Tim J. van der Zee, Paolo Tecchio, Daniel Hahn, B. Raiteri","doi":"10.1101/2024.08.07.607010","DOIUrl":"https://doi.org/10.1101/2024.08.07.607010","url":null,"abstract":"Background Brightness-mode (B-mode) ultrasound is a valuable tool to non-invasively image skeletal muscle architectural changes during movement, but automatically estimating architectural features such as fascicle length remains a major challenge. Existing fascicle tracking algorithms either require time-consuming drift corrections or yield noisy estimates that require post-processing. We therefore aimed to develop an algorithm that tracks fascicles without drift and noise across a range of experimental conditions and image acquisition settings. Methods We applied a Kalman filter to combine fascicle length and fascicle angle estimates from existing and openly available UltraTrack and TimTrack algorithms into a hybrid algorithm called UltraTimTrack. We applied the hybrid algorithm to ultrasound image sequences collected from the human medial gastrocnemius of healthy individuals (N=8, 4 women), who performed cyclical submaximal plantar flexion contractions or remained at rest during passive ankle joint rotations at given frequencies and amplitudes whilst seated in a dynamometer chair. We quantified the algorithm’s tracking accuracy, noise, and drift as the respective mean, cycle-to-cycle, and accumulated between-contraction variability in fascicle length and fascicle angle. We expected UltraTimTrack’s estimates to be less noisy and to drift less across experimental conditions and image acquisition settings, compared with estimates from its parent algorithms. Results The proposed algorithm had low-noise estimates like UltraTrack and was drift-free like TimTrack across the broad range of conditions we tested. Estimated fascicle length and fascicle angle deviations accumulated to 2.1 ± 1.3 mm (mean ± s.d.) and 0.8 ± 0.7 deg, respectively, over 120 cyclical contractions. Average cycle-to-cycle variability was 1.4 ± 0.4 mm and 0.6 ± 0.3 deg, respectively. In comparison, UltraTrack had similar cycle-to-cycle variability (1.1 ± 0.3 mm, 0.5 ± 0.1 deg) but greater cumulative deviation (67.0 ± 59.3 mm, 9.3 ± 8.6 deg), whereas TimTrack had similar cumulative deviation (1.9 ± 2.2 mm, 0.9 ± 1.0 deg) but greater variability (3.5 ± 1.0 mm, 1.4 ± 0.5 deg). UltraTimTrack was significantly less affected by experimental conditions and image acquisition settings than its parent algorithms. It also performed well on a previously published image sequence from the human tibialis anterior, yielding a smaller root-mean-square deviation from manual tracking (fascicle length: 2.7 mm, fascicle angle: 0.7 deg) than a recently proposed hybrid algorithm (fascicle length: 4.5 mm, fascicle angle: 0.8 deg) and a machine-learning (DL_Track) algorithm (fascicle length: 8.2 mm, fascicle angle: 4.8 deg). Conclusion We developed a Kalman-filter-based method to improve fascicle tracking from B-mode ultrasound image sequences. The proposed algorithm provides low-noise, drift-free estimates of muscle architectural changes that may better inform muscle function interpretations.","PeriodicalId":505198,"journal":{"name":"bioRxiv","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141922706","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}