bioRxiv : the preprint server for biology最新文献_第7页

Data Processing in Multidimensional MRI For Biomarker Identification: Is It Necessary?

bioRxiv : the preprint server for biology Pub Date : 2025-03-29 DOI: 10.1101/2025.03.25.645236

Kristofor Pas, Dan Benjamini, Peter Basser, Gustavo Rohde

{"title":"Data Processing in Multidimensional MRI For Biomarker Identification: Is It Necessary?","authors":"Kristofor Pas, Dan Benjamini, Peter Basser, Gustavo Rohde","doi":"10.1101/2025.03.25.645236","DOIUrl":"https://doi.org/10.1101/2025.03.25.645236","url":null,"abstract":"Multidimensional MRI (MD-MRI) is an emerging technique that holds promise for identifying tissue characteristics that could be indicative of pathologies. Before these characteristics can be interpreted, MD-MRI measurements are converted into an spectrum. These spectra are then utilized to obtain some understanding of the underlying tissue microstructure, often through the use of statistical, machine learning, and mathematical modeling methods. The aim of this study was to compare outcomes of using unprocessed MDMRI signals for statistical regression in comparison to the corresponding spectra. Backed by a theoretical argument, we described an experimental procedure regressing both MDMRI signals and spectra to histological outcomes intrasubject. Through using multiple conventional ML methods, and a proposed method using convex sets, we aimed to see which yielded the highest accuracy. Both theory and experimental evidence suggest that, without a priori information, statistical regression was best performed on the MDMRI signal. We conclude, barring any a priori information regarding tissue changes, there is no significant advantage to performing regression analysis on reconstructed spectra in the process of biomarker identification.","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11974882/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143805188","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}

引用次数: 0

BLADE-R: streamlined RNA extraction for molecular diagnostics and high-throughput applications. BLADE-R：用于分子诊断和高通量应用的简化 RNA 提取。

bioRxiv : the preprint server for biology Pub Date : 2025-03-29 DOI: 10.1101/2025.03.27.645479

Anam Tajammal, Samuel Haddox, Shafaque Zahra, Robert Cornelison, Adelaide Ohui Fierti, Hui Li

{"title":"BLADE-R: streamlined RNA extraction for molecular diagnostics and high-throughput applications.","authors":"Anam Tajammal, Samuel Haddox, Shafaque Zahra, Robert Cornelison, Adelaide Ohui Fierti, Hui Li","doi":"10.1101/2025.03.27.645479","DOIUrl":"https://doi.org/10.1101/2025.03.27.645479","url":null,"abstract":"Efficient nucleic acid extraction and purification are crucial for cellular and molecular biology research, yet they pose challenges for large-scale clinical RNA sequencing and PCR assays. Here, we present BLADE-R, a magnetic bead-based protocol that simplifies the process by combining cellular lysis and nucleic acid binding into a single step, followed by a unique on-bead rinse for nuclease-free separation of genomic DNA and RNA. The Agilent TapeStation and RT-qPCR analyses show that RNA extracted from HEK293T cell line using BLADE-R outperforms the TRIzol protocol in terms of time and cost. RNA sequencing reveals no differences in sequence quality or gene count variance between samples processed with BLADE-R and those processed with TRIzol followed by RNA kit clean-up. Additionally, BLADE-R outperformed TRIzol in RNA extraction from frozen tissue and whole blood samples, as confirmed by RT-qPCR. Our protocol can be adapted to a 96-well plate format, enabling RNA purification of up to 96 human blood samples in less time than a single-sample traditional extraction. Using BLADE-R in this format, we confirmed minimal well-to-well contamination in RNA purification, cDNA synthesis, and PCR. Therefore, our novel BLADE-R protocol, suitable for both low and high-throughput formats, is effective even in limited-resource settings for preparing clinical samples for PCR and sequencing assays. Thus, our new BLADE-R technique works well even in low-resource environments to prepare clinical samples for PCR and sequencing experiments. It can be adapted for both low- and high-throughput formats.","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11974778/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143805343","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}

引用次数: 0

Synaptic editing of frontostriatal circuitry prevents excessive grooming in SAPAP3-deficient mice.

bioRxiv : the preprint server for biology Pub Date : 2025-03-29 DOI: 10.1101/2025.03.27.645613

Kathryn K Walder-Christensen, Hannah A Soliman, Nicole Calakos, Kafui Dzirasa

引用次数: 0

Three-dimensional cellularization in chytrid fungi uses distinct mechanisms from those driving one- and two-dimensional cytokinesis in animals and yeast. 糜烂真菌的三维细胞化采用了与动物和酵母的一维和二维细胞分裂不同的驱动机制。

bioRxiv : the preprint server for biology Pub Date : 2025-03-29 DOI: 10.1101/2025.01.30.635136

Edgar M Medina, Mary W Elting, Lillian Fritz-Laylin

{"title":"Three-dimensional cellularization in chytrid fungi uses distinct mechanisms from those driving one- and two-dimensional cytokinesis in animals and yeast.","authors":"Edgar M Medina, Mary W Elting, Lillian Fritz-Laylin","doi":"10.1101/2025.01.30.635136","DOIUrl":"https://doi.org/10.1101/2025.01.30.635136","url":null,"abstract":"Chytrid fungi provide a model for studying three-dimensional cellularization, where nuclei that are dispersed throughout the cytoplasm are synchronously compartmentalized into daughter cells. This organization poses geometric challenges not faced by cells undergoing conventional cytokinesis or Drosophila cellularization, where nuclei are organized in one- or two-dimensional arrangements. We use the chytrid Spizellomyces punctatus to show that chytrid cellularization begins with nuclei and centrosomes migrating to the plasma membrane, where centrosome-associated vesicles define sites of membrane invagination. The resulting tubular furrows extend, creating a foam-like tessellation of polyhedral compartments, each with a nucleus and cilium. Using inhibitors and laser ablation, we show that actomyosin networks drive cellularization, while microtubules pattern but are not essential for cellularization. Finally, we suggest that chytrids may have incorporated mechanisms associated with ciliogenesis in animals to coordinate the association of internal nuclei with actomyosin networks and membranes to solve the unique challenges associated with three-dimensional cellularization.","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11974727/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143805485","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}

引用次数: 0

Alpha-actinin-1 stabilizes focal adhesions to facilitate sarcomere assembly in cardiac myocytes.

bioRxiv : the preprint server for biology Pub Date : 2025-03-29 DOI: 10.1101/2025.03.28.645933

James B Hayes, Anna M Bainbridge, Dylan T Burnette

{"title":"Alpha-actinin-1 stabilizes focal adhesions to facilitate sarcomere assembly in cardiac myocytes.","authors":"James B Hayes, Anna M Bainbridge, Dylan T Burnette","doi":"10.1101/2025.03.28.645933","DOIUrl":"https://doi.org/10.1101/2025.03.28.645933","url":null,"abstract":"Cardiac sarcomere assembly is a highly orchestrated process requiring integration between intracellular contractile components and extracellular adhesions. While α-actinin-2 (ACTN2) is well known for its structural role at Z-discs, the function of the \"non-muscle\" paralog α-actinin-1 (ACTN1) in cardiomyocytes remains unclear. Using human induced pluripotent stem cell-derived cardiac myocytes (hiCMs), we demonstrate that ACTN1 is essential for sarcomere assembly. siRNA-mediated depletion of ACTN1 disrupted Z-line formation and impaired sarcomere organization, defects that were rescued by exogenous ACTN1 but not ACTN2, revealing non-redundant functions. Unlike ACTN2, ACTN1 localized predominantly to focal adhesions and was required for adhesion maturation, as evidenced by reduced adhesion size and number following ACTN1 depletion. Live-cell imaging of vinculin dynamics showed decreased stability of adhesion-associated vinculin in ACTN1-deficient cells, whereas paxillin dynamics were unaffected. These results suggest that ACTN1 stabilizes focal adhesions to promote effective force transmission during sarcomere assembly.","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11974845/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143804808","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}

引用次数: 0

IL-25-induced memory ILC2s mediate long-term small intestinal adaptation.

bioRxiv : the preprint server for biology Pub Date : 2025-03-29 DOI: 10.1101/2025.03.25.645270

Victor S Cortez, Sara Viragova, Satoshi Koga, Meizi Liu, Claire E O'Leary, Roberto R Ricardo-Gonzalez, Andrew W Schroeder, Nathan Kochhar, Ophir D Klein, Michael S Diamond, Hong-Erh Liang, Richard M Locksley

{"title":"IL-25-induced memory ILC2s mediate long-term small intestinal adaptation.","authors":"Victor S Cortez, Sara Viragova, Satoshi Koga, Meizi Liu, Claire E O'Leary, Roberto R Ricardo-Gonzalez, Andrew W Schroeder, Nathan Kochhar, Ophir D Klein, Michael S Diamond, Hong-Erh Liang, Richard M Locksley","doi":"10.1101/2025.03.25.645270","DOIUrl":"https://doi.org/10.1101/2025.03.25.645270","url":null,"abstract":"The adaptation of intestinal helminths to vertebrates evolved strategies to attenuate host tissue damage to support reproductive needs of parasites necessary to disseminate offspring to the environment. Helminths initiate the IL-25-mediated tuft cell-ILC2 circuit that enhances barrier protection of the host although viable parasites can target and limit the pathway. We used IL-25 to create small intestinal adaptation marked by anatomic, cell compositional and immunologic changes that persisted months after induction. Small intestinal adaptation was associated with heightened resistance to barrier pathogens, including in the lung, and sustained by transcriptionally and epigenetically modified, tissue-resident, memory-effector ILC2s distinct from those described by innate 'training'; epithelial stem cells remained unaltered. Despite requiring IL-25 for induction, memory ILC2s maintained an activated state in the absence of multiple alarmins and supported mucosal resilience while avoiding adverse sensitization to chronic inflammation, revealing a pathway for deploying innate immune cells to coordinate a distributed mucosal defense.","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11974837/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143805213","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}

引用次数: 0

Suspended Tissue Open Microfluidic Patterning (STOMP). 悬浮组织开放式微流控芯片（STOMP）。

bioRxiv : the preprint server for biology Pub Date : 2025-03-29 DOI: 10.1101/2024.10.04.616662

Amanda J Haack, Lauren G Brown, Alex J Goldstein, Priti Mulimani, Jean Berthier, Asha R Viswanathan, Irina Kopyeva, Jamison M Whitten, Ariel Lin, Serena H Nguyen, Thomas P Leahy, Ella E Bouker, Ruby M Padgett, Natalie A Mazzawi, Jodie C Tokihiro, Ross C Bretherton, Aaliyah Wu, Stephen J Tapscott, Cole A DeForest, Tracy E Popowics, Erwin Berthier, Nathan J Sniadecki, Ashleigh B Theberge

{"title":"Suspended Tissue Open Microfluidic Patterning (STOMP).","authors":"Amanda J Haack, Lauren G Brown, Alex J Goldstein, Priti Mulimani, Jean Berthier, Asha R Viswanathan, Irina Kopyeva, Jamison M Whitten, Ariel Lin, Serena H Nguyen, Thomas P Leahy, Ella E Bouker, Ruby M Padgett, Natalie A Mazzawi, Jodie C Tokihiro, Ross C Bretherton, Aaliyah Wu, Stephen J Tapscott, Cole A DeForest, Tracy E Popowics, Erwin Berthier, Nathan J Sniadecki, Ashleigh B Theberge","doi":"10.1101/2024.10.04.616662","DOIUrl":"10.1101/2024.10.04.616662","url":null,"abstract":"Free-standing tissue structures tethered between pillars are powerful mechanobiology tools for studying cell contraction. To model interfaces ubiquitous in natural tissues and upgrade existing single-region suspended constructs, we developed Suspended Tissue Open Microfluidic Patterning (STOMP), a method to create multi-regional suspended tissues. STOMP uses open microfluidics and capillary pinning to pattern subregions within free-standing tissues, facilitating the study of complex tissue interfaces, such as diseased-healthy boundaries (e.g., fibrotic-healthy) and tissue-type interfaces (e.g., bone-ligament). We observed altered contractile dynamics in fibrotic-healthy engineered heart tissues compared to single-region tissues and differing contractility in bone-ligament enthesis constructs compared to single-tissue periodontal ligament models. STOMP is a versatile platform - surface tension-driven patterning removes material requirements common with other patterning methods (e.g., shear-thinning, photopolymerizable) allowing tissue generation in multiple geometries with native extracellular matrices and advanced 4D materials. STOMP combines the contractile functionality of suspended tissues with precise patterning, enabling dynamic and spatially controlled studies.","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11482760/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142485523","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}

引用次数: 0

Multiple Wnt signaling pathways direct epithelial tubule interconnection in the regenerating zebrafish kidney.

bioRxiv : the preprint server for biology Pub Date : 2025-03-29 DOI: 10.1101/2025.03.26.645545

Caramai N Kamei, William G B Sampson, Carolin Albertz, Oliver Aries, Amber Wolf, Rohan M Upadhyay, Samuel M Hughes, Heiko Schenk, Frederic Bonnet, Bruce W Draper, Kyle W McCracken, Denise K Marciano, Leif Oxburgh, Iain A Drummond

{"title":"Multiple Wnt signaling pathways direct epithelial tubule interconnection in the regenerating zebrafish kidney.","authors":"Caramai N Kamei, William G B Sampson, Carolin Albertz, Oliver Aries, Amber Wolf, Rohan M Upadhyay, Samuel M Hughes, Heiko Schenk, Frederic Bonnet, Bruce W Draper, Kyle W McCracken, Denise K Marciano, Leif Oxburgh, Iain A Drummond","doi":"10.1101/2025.03.26.645545","DOIUrl":"https://doi.org/10.1101/2025.03.26.645545","url":null,"abstract":"Epithelial tubule fusion is fundamental for kidney morphogenesis. Differentiating nephron tubules interconnect with collecting system epithelia to generate a lumenal pathway for fluid excretion. In the adult zebrafish kidney, nephrogenesis occurs as a regenerative response to injury and provides a model to explore cell signaling pathways required for tubule interconnection. We show that canonical Wnt signaling at the junction between two tubules induces a mesenchymal, invasive cell phenotype and is required, along with Src kinase and rac1, to generate basal cell protrusions. The Wnt ligands wnt9b and wnt4 are both required for new nephron formation after injury. Mutation in wnt4 or treatment with the canonical Wnt inhibitor IWR1 blocks formation of basal protrusions in forming nephrons. Mutation in the Wnt receptor frizzled9b reveals a fusion-associated non-canonical Wnt pathway that acts to 1) restrict canonical Wnt gene expression, 2) drive Rho kinase-dependent apical constriction of epithelial cells, and 3) position basal protrusions and generate orthogonal tubule lumenal connections. As a result, frizzled9b mutant nephrons fail to fully interconnect with target distal tubules. Our results indicate that canonical and non-canonical Wnt signaling interact in the same cells to orient and drive tubule interconnection in the regenerating zebrafish kidney.","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11974930/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143805186","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}

引用次数: 0

Epistatic impacts of cis - and trans -regulatory mutations on the distribution of mutational effects for gene expression in Saccharomyces cerevisiae.

bioRxiv : the preprint server for biology Pub Date : 2025-03-29 DOI: 10.1101/2025.03.26.645465

Eden McQueen, Bing Yang, Patricia J Wittkopp

{"title":"Epistatic impacts of cis - and trans -regulatory mutations on the distribution of mutational effects for gene expression in Saccharomyces cerevisiae.","authors":"Eden McQueen, Bing Yang, Patricia J Wittkopp","doi":"10.1101/2025.03.26.645465","DOIUrl":"https://doi.org/10.1101/2025.03.26.645465","url":null,"abstract":"Epistasis can influence evolution by causing the distribution of phenotypic effects for new mutations to vary among genotypes. Here, we investigate how epistatic interactions between new mutations and an existing regulatory mutation might impact the evolution of gene expression using Saccharomyces cerevisiae. We do so by estimating the distribution of mutational effects for expression of a fluorescent reporter protein driven by the S. cerevisiae TDH3 promoter in a reference strain as well as in eight mutant strains. Each of the mutant strains differed from the reference strain by a single mutation affecting expression of the focal gene. We found that half of these regulatory mutations changed the variance and/or skewness of the distribution of mutational effects. A change in variance indicates a change in mutational robustness, and we found that one initial regulatory mutation increased mutational robustness while another decreased it. A change in skewness indicates a change in the relative frequency and/or effect size of mutations increasing or decreasing expression, and we found that the initial regulatory mutation in four strains had such an effect. Strikingly, in all four of these cases, the change in skewness increased the likelihood that new mutations would at least partially compensate for the effects of the initial regulatory mutation. If this form of epistatic impact on the distribution of mutational effects is common, it could provide a neutral mechanism reducing the divergence of gene expression and help explain the prevalence of alleles with compensatory effects in natural populations of S. cerevisiae .","PeriodicalId":519960,"journal":{"name":"bioRxiv : the preprint server for biology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11974906/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143805373","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}

引用次数: 0

Structured Random Binding: a minimal model of protein-protein interactions. 结构化随机结合：蛋白质-蛋白质相互作用的最小模型。

bioRxiv : the preprint server for biology Pub Date : 2025-03-29 DOI: 10.1101/2025.03.26.645477

Ling-Nan Zou

引用次数: 0