Integrative Biology最新文献

{"title":"The cellular zeta potential: cell electrophysiology beyond the membrane.","authors":"Michael Pycraft Hughes","doi":"10.1093/intbio/zyae003","DOIUrl":"10.1093/intbio/zyae003","url":null,"abstract":"<p><p>The standard model of the cell membrane potential Vm describes it as arising from diffusion currents across a membrane with a constant electric field, with zero electric field outside the cell membrane. However, the influence of Vm has been shown to extend into the extracellular space where it alters the cell's ζ-potential, the electrical potential measured a few nm from the cell surface which defines how the cell interacts with charged entities in its environment, including ions, molecules, and other cells. The paradigm arising from surface science is that the ζ-potential arises only from fixed membrane surface charge, and has consequently received little interest. However, if the ζ-potential can mechanistically and dynamically change by alteration of Vm, it allows the cell to dynamically alter cell-cell and cell-molecule interactions and may explain previously unexplained electrophysiological behaviours. Whilst the two potentials Vm and ζ are rarely reported together, they are occasionally described in different studies for the same cell type. By considering published data on these parameters across multiple cell types, as well as incidences of unexplained but seemingly functional Vm changes correlating with changes in cell behaviour, evidence is presented that this may play a functional role in the physiology of red blood cells, macrophages, platelets, sperm, ova, bacteria and cancer. Understanding how these properties will improve understanding of the role of electrical potentials and charges in the regulation of cell function and in the way in which cells interact with their environment. Insight  The zeta (ζ) potential is the electrical potential a few nm beyond the surface of any suspensoid in water. Whilst typically assumed to arise only from fixed charges on the cell surface, recent and historical evidence shows a strong link to the cell's membrane potential Vm, which the cell can alter mechanistically through the use of ion channels. Whilst these two potentials have rarely been studied simultaneously, this review collates data across multiple studies reporting Vm, ζ-potential, electrical properties of changes in cell behaviour. Collectively, this points to Vm-mediated ζ-potential playing a significant role in the physiology and activity of blood cells, immune response, developmental biology and egg fertilization, and cancer among others.</p>","PeriodicalId":80,"journal":{"name":"Integrative Biology","volume":"16 ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139641216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: The cellular zeta potential: cell electrophysiology beyond the membrane.","authors":"","doi":"10.1093/intbio/zyae006","DOIUrl":"https://doi.org/10.1093/intbio/zyae006","url":null,"abstract":"","PeriodicalId":80,"journal":{"name":"Integrative Biology","volume":"16 ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140011677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated analysis revealing novel associations between dietary patterns and the immune system in older adults.","authors":"Jessica Conway, Animesh Acharjee, Niharika A Duggal","doi":"10.1093/intbio/zyae010","DOIUrl":"10.1093/intbio/zyae010","url":null,"abstract":"<p><p>With the expanding ageing population, there is a growing interest in the maintenance of immune health to support healthy ageing. Enthusiasm exists for unravelling the impact of diet on the immune system and its therapeutic potential. However, a key challenge is the lack of studies investigating the effect of dietary patterns and nutrients on immune responses. Thus, we have used an integrative analysis approach to improve our understanding of diet-immune system interactions in older adults. To do so, dietary data were collected in parallel with performing immunophenotyping and functional assays from healthy older (n = 40) participants. Food Frequency Questionnaire (FFQ) was utilised to derive food group intake and multi-colour flow cytometry was performed for immune phenotypic and functional analysis. Spearman correlation revealed the strength of association between all combinations of dietary components, micronutrients, and hallmarks of immunesenescence. In this study, we propose for the first time that higher adherence to the Mediterranean diet is associated with a positive immune-ageing trajectory (Lower IMM-AGE score) in older adults due to the immune protective effects of high dietary fibre and PUFA intake in combating accumulation or pro-inflammatory senescent T cells. Furthermore, a diet rich in Vit A, Vit B6 and Vit B12 is associated with fewer features of immunesenescence [such as accumulation of terminally differentiated memory CD8 T cells] in older adults. Based on our findings we propose a future nutrition-based intervention study evaluating the efficacy of adherence to the MED diet alongside a multi-nutrient supplementation on immune ageing in older adults to set reliable dietary recommendations with policymakers that can be given to geriatricians and older adults. Insight box: There is a growing interest in the maintenance of immune health to boost healthy ageing. However, a key challenge is the lack of studies investigating the effect of dietary patterns and nutrients on immune responses. Thus, to do so we collected dietary data in parallel with performing immunophenotyping and functional assays on healthy older (n = 40) participants, followed by an integrative analysis approach to improve our understanding of diet-immune system interactions in older adults. We strongly believe that these new findings are appropriate for IB and will be of considerable interest to its broad audience.</p>","PeriodicalId":80,"journal":{"name":"Integrative Biology","volume":"16 ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141173749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional characterization of novel RbTI gene from ricebean and validation of its insecticidal properties in transgenic tobacco.","authors":"Rajan Katoch, Sunil Kumar Singh, Kiran Raj, Sandeep Kumar, Neelam Thakur, Vipin Hallan, Sudesh Kumar","doi":"10.1093/intbio/zyae017","DOIUrl":"https://doi.org/10.1093/intbio/zyae017","url":null,"abstract":"<p><p>Plant protease inhibitors (PI's) inhibit the activity of gut proteases and thus provide resistance against insect attack. Previously we have published first report on cloning and characterization of a novel Bowman-Birk protease inhibitor gene (RbTI) from ricebean (Vigna umbellata). In this study, the RbTI gene was further characterized and validated as a potential candidate for transferring insect resistance in economically important crops. We have successfully generated transgenic tobacco plants expressing RbTI gene constitutively under CaMV35S promoter using Agrobacterium transformation. Genomic PCR and GUS analysis confirmed the successful integration of RbTI gene into tobacco plant genome. qRT-PCR analysis revealed highest RbTI gene expression in transformed tobacco leaves nearing maturity. Feeding of transformed tobacco leaf tissue showed prominent effect on larval mortality throughout the larval growth stages mainly during first three days of feeding. For functional analysis of RbTI gene, we estimated the inhibitory activity of protein extracts from normal and transformed tobacco plants against gut proteases of Spodoptera litura and H. armigera larval instars. Maximum inhibition of trypsin (82.42% and 73.25%) and chymotrypsin (69.50% and 60.64%) enzymes was recorded at early larval stages of both insects. The results of this study validated the future use of RbTI gene from ricebean legume as a potential candidate for transferring insect resistance in economically important crops. Insight, innovation, integration: Present study was conducted with the aim to utilize the state of art biotechnological techniques for transferring key pest resistant genes from underutilized promising crop ricebean. The tobacco plant has been utilized as modern plant for proof of concept where a protease inhibitor gene from Ricebean has been transferred to tobacco plant which induced larval mortality within first three days of feeding at all larval developmental stages. The biochemical assays on mid-gut total protein extract showed that the transgenic tobacco leaves have inhibiting effect on trypsin and chymotrypsin enzymes of insect which is otherwise required for digestion of food by them. Hence, we provide a novel gene that could be utilized for pest resistance in other crops different developmental stages.</p>","PeriodicalId":80,"journal":{"name":"Integrative Biology","volume":"16 ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting IKZF1 via HDAC1: Combating Acute Myeloid Leukemia.","authors":"Sathyanarayan Balaji, Suvitha Anbarasu, Sudha Ramaiah, Anand Anbarasu","doi":"10.1093/intbio/zyae022","DOIUrl":"https://doi.org/10.1093/intbio/zyae022","url":null,"abstract":"<p><p>Acute myeloid leukemia (AML) accounts for 1.3% of all cancers, with a limited survival of only 30%, and treating AML is a continuous challenge in medicine. IKZF1 is a DNA-binding protein that is highly mutated and undruggable but significant in causing AML. The current study aims to target its transcription factors (TFs) modulating IKZF1 activity. The TF network was constructed and analyzed which revealed a dense Markov cluster (MCL) cluster and five hub genes namely, HDAC1, EP300, CREBBP, TP53, and MYC; the first node clusters were generated for the hub genes. Functional enrichment analysis found AML pathway enriched in all the clusters. Gene ontology terms were majorly related to transcription regulation terms including RNA polymerase transcription regulation, DNA binding activity, DNA templated transcription, and transcription factor binding. Further, the mutation profile of all the TFs found HDAC1 with a very low mutation profile of 0.1% and the survival plot found HDAC1 with a hazard ratio of 1.17 with increased survival upon low expression. Also, among the hub genes, HDAC1 was the only first node interactor with IKZF1. Thus, HDAC1 could be a potential biomarker candidate as well as a key target in treating AML. Insight Box The study has an integrated approach for identifying a potential target through network analysis, functional enrichment analysis, mutation profiling survival prognosis, and target screening. The study employs a better strategy for targeting IKZF1, a significantly upregulated gene in AML by regulating its transcription factors. The analysis revealed a network of TFs regulating IKZF1, among which HDAC1 emerged as a promising candidate due to its low mutation rate, association with better survival outcomes, and direct interaction with IKZF1. This suggests HDAC1 could be a valuable biomarker and therapeutic target for AML treatment.</p>","PeriodicalId":80,"journal":{"name":"Integrative Biology","volume":"16 ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142826738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: Mimicking the topography of the epidermal-dermal interface with elastomer substrates.","authors":"","doi":"10.1093/intbio/zyae004","DOIUrl":"10.1093/intbio/zyae004","url":null,"abstract":"","PeriodicalId":80,"journal":{"name":"Integrative Biology","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139690745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An integrative biology approach to understanding keratinocyte collective migration as stimulated by bioglass.","authors":"","doi":"10.1093/intbio/zyae009","DOIUrl":"https://doi.org/10.1093/intbio/zyae009","url":null,"abstract":"","PeriodicalId":80,"journal":{"name":"Integrative Biology","volume":"16 ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140853559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modeling Shiga toxin-induced human renal-specific microvascular injury.","authors":"Russell Whelan, Daniel Lih, Jun Xue, Jonathan Himmelfarb, Ying Zheng","doi":"10.1093/intbio/zyae001","DOIUrl":"10.1093/intbio/zyae001","url":null,"abstract":"<p><p>Shiga toxin (Stx) causes significant renal microvascular injury and kidney failure in the pediatric population, and an effective targeted therapy has yet to be demonstrated. Here we established a human kidney microvascular endothelial cell line for the study of Stx mediated injuries with respect to their morphologic, phenotypic, and transcriptional changes, and modeled Stx induced thrombotic microangiopathy (TMA) in flow-mediated 3D microvessels. Distinct from other endothelial cell lines, both isolated primary and immortalized human kidney microvascular endothelial cells demonstrate robust cell-surface expression of the Stx receptor Gb3, and concomitant dose-dependent toxicity to Stx, with significant contributions from caspase-dependent cell death. Use of a glucosylceramide synthase inhibitor (GCSi) to target disruption of the synthetic pathway of Gb3 resulted in remarkable protection of kidney microvascular cells from Stx injury, shown in both cellular morphologies, caspase activation and transcriptional analysis from RNA sequencing. Importantly, these findings are recapitulated in 3D engineered kidney microvessels under flow. Moreover, whole blood perfusion through Stx-treated microvessels led to marked platelet binding on the vessel wall, which was significantly reduced with the treatment of GCSi. These results validate the feasibility and utility of a bioengineered ex vivo human microvascular model under flow to recapitulate relevant blood-endothelial interactions in STEC-HUS. The profound protection afforded by GCSi demonstrates a preclinical opportunity for investigation in human tissue approximating physiologic conditions. Moreover, this work provides a broad foundation for novel investigation into TMA injury pathogenesis and treatment. Insight Box: Shiga toxin (Stx) causes endothelial injury that results in significant morbidity and mortality in the pediatric population, with no effective targeted therapy. This paper utilizes human kidney microvascular cells to examine Stx mediated cell death in both 2D culture and flow-mediated 3D microvessels, with injured microvessels also developing marked platelet binding and thrombi formation when perfused with blood, consistent with the clinical picture of HUS. This injury is abrogated with a small molecule inhibitor targeting the synthetic pathway of the Shiga toxin receptor. Our findings shed light onto Stx-induced vascular injuries and pave a way for broad investigation into thrombotic microangiopathies.</p>","PeriodicalId":80,"journal":{"name":"Integrative Biology","volume":"16 ","pages":""},"PeriodicalIF":1.5,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11458155/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139544881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Vicsek-type model of confined cancer cells with variable clustering affinities.","authors":"Zachary Kirchner, Anna Geohagan, Agnieszka Truszkowska","doi":"10.1093/intbio/zyae005","DOIUrl":"https://doi.org/10.1093/intbio/zyae005","url":null,"abstract":"<p><p>Clustering of cells is an essential component of many biological processes from tissue formation to cancer metastasis. We develop a minimal, Vicsek-based model of cellular interactions that robustly and accurately captures the variable propensity of different cells to form groups when confined. We calibrate and validate the model with experimental data on clustering affinities of four lines of tumor cells. We then show that cell clustering or separation tendencies are retained in environments with higher cell number densities and in cell mixtures. Finally, we calibrate our model with experimental measurements on the separation of cells treated with anti-clustering agents and find that treated cells maintain their distances in denser suspensions. We show that the model reconstructs several cell interaction mechanisms, which makes it suitable for exploring the dynamics of cell cluster formation as well as cell separation. Insight: We developed a model of cellular interactions that captures the clustering and separation of cells in an enclosure. Our model is particularly relevant for microfluidic systems with confined cells and we centered our work around one such emerging assay for the detection and research on clustering breast cancer cells. We calibrated our model using the existing experimental data and used it to explore the functionality of the assay under a broader set of conditions than originally considered. Future usages of our model can include purely theoretical and computational considerations, exploring experimental devices, and supporting research on small to medium-sized cell clusters.</p>","PeriodicalId":80,"journal":{"name":"Integrative Biology","volume":"16 ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139970027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Continuum interpretation of mechano-adaptation in micropatterned epithelia informed by in vitro experiments.","authors":"Bernard L Cook,&nbsp;Patrick W Alford","doi":"10.1093/intbio/zyad009","DOIUrl":"https://doi.org/10.1093/intbio/zyad009","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Epithelial tissues adapt their form and function following mechanical perturbations, or mechano-adapt, and these changes often result in reactive forces that oppose the direction of the applied change. Tissues subjected to ectopic tensions, for example, employ behaviors that lower tension, such as increasing proliferation or actomyosin turnover. This oppositional behavior suggests that the tissue has a mechanical homeostasis. Whether attributed to maintenance of cellular area, cell density, or cell and tissue tensions, epithelial mechanical homeostasis has been implicated in coordinating embryonic morphogenesis, wound healing, and maintenance of adult tissues. Despite advances toward understanding the feedback between mechanical state and tissue response in epithelia, more work remains to be done to examine how tissues regulate mechanical homeostasis using epithelial sheets with defined micropatterned shapes. Here, we used cellular microbiaxial stretching (CμBS) to investigate mechano-adaptation in micropatterned tissues of different shape consisting of Madin-Darby canine kidney cells. Using the CμBS platform, tissues were subjected to a 30% stretch that was held for 24 h. We found that, following stretch, tissue stresses immediately increased then slowly evolved over time, approaching their pre-stretch values by 24 h. Organization of the actin cytoskeletal was found to play a role in this process: anisotropic ally structured tissues exhibited anisotropic stress patterns, and the cytoskeletal became more aligned following stretch and reorganized over time. Interestingly, in unstretched tissues, stresses also decreased, which was found to be driven by proliferation-induced cellular confinement and change in tissue thickness. We modeled these behaviors with a continuum-based model of epithelial growth that accounted for stress-induced actin remodeling and proliferation, and found this model to strongly capture experimental behavior. Ultimately, this combined experimental-modeling approach suggests that epithelial mechano-adaptation depends on cellular architecture and proliferation, which can be modeled with a field-averaged approach applicable to more specific contexts in which change is driven by epithelial mechanical homeostasis. Insight box Epithelial tissues adapt their form and function following mechanical perturbation, and it is thought that this 'mechano-adaptation' plays an important role in driving processes like embryonic morphogenesis, wound healing, and adult tissue maintenance. Here, we use cellular microbiaxial stretching to probe this process in vitro in small epithelial tissues whose geometries were both controlled and varied. By using a highly precise stretching device and a continuum mechanics modeling framework, we revealed that tissue mechanical state changes following stretch and over time, and that this behavior can be explained by stress-dependent changes in actin fibers and proliferation. Integration of these approac","PeriodicalId":80,"journal":{"name":"Integrative Biology","volume":"15 ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2023-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10318950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}