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Geometry-sensitive protrusion growth directs confined cell migration 几何敏感的突起生长指导有限的细胞迁移
arXiv - QuanBio - Subcellular Processes Pub Date : 2023-08-16 DOI: arxiv-2308.08372
Johannes Flommersfeld, Stefan Stöberl, Omar Shah, Joachim O. Rädler, Chase P. Broedersz
{"title":"Geometry-sensitive protrusion growth directs confined cell migration","authors":"Johannes Flommersfeld, Stefan Stöberl, Omar Shah, Joachim O. Rädler, Chase P. Broedersz","doi":"arxiv-2308.08372","DOIUrl":"https://doi.org/arxiv-2308.08372","url":null,"abstract":"The migratory dynamics of cells can be influenced by the complex\u0000micro-environment through which they move. It remains unclear how the motility\u0000machinery of confined cells responds and adapts to their micro-environment.\u0000Here, we propose a biophysical mechanism for a geometry-dependent coupling\u0000between the front of the cell and the nucleus that leads to directed migration.\u0000We apply our model to geometry-guided cell migration to obtain insights into\u0000the origin of directed migration on asymmetric adhesive micro-patterns and the\u0000polarization enhancement of cells observed under strong confinement.\u0000Remarkably, for cells that can choose between channels of different size, our\u0000model predicts an intricate dependence for cellular decision making as a\u0000function of the two channel widths, which we confirm experimentally.","PeriodicalId":501170,"journal":{"name":"arXiv - QuanBio - Subcellular Processes","volume":"58 44","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138510938","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}
引用次数: 0
UQSA -- An R-Package for Uncertainty Quantification and Sensitivity Analysis for Biochemical Reaction Network Models UQSA——一个用于生化反应网络模型不确定度定量和敏感性分析的r包
arXiv - QuanBio - Subcellular Processes Pub Date : 2023-08-10 DOI: arxiv-2308.05527
Andrei Kramer, Federica Milinanni, Pierre Nyquist, Alexandra Jauhiainen, Olivia Eriksson
{"title":"UQSA -- An R-Package for Uncertainty Quantification and Sensitivity Analysis for Biochemical Reaction Network Models","authors":"Andrei Kramer, Federica Milinanni, Pierre Nyquist, Alexandra Jauhiainen, Olivia Eriksson","doi":"arxiv-2308.05527","DOIUrl":"https://doi.org/arxiv-2308.05527","url":null,"abstract":"We present an R-package developed for modeling of biochemical reaction\u0000networks, uncertainty quantification (UQ) and sensitivity analysis (SA).\u0000Estimating parameters and quantifying their uncertainty (and resulting\u0000prediction uncertainty), is required for data-driven systems biology modeling.\u0000Sampling methods need to be efficient when confronted with high-dimensional,\u0000correlated parameter distributions. We have developed the UQSA package to be\u0000fast for this problem class and work well with other tools for modelling. We\u0000aim for simplicity, and part of that is our use of the SBtab format for the\u0000unified storage of model and data. Our tool-set is modular enough, that parts\u0000can be replaced. We use intermediate formats that are not hidden from the user\u0000to make this feasible. UQ is performed through Markov chain Monte Carlo (MCMC)\u0000sampling in an Approximate Bayesian Computation (ABC) setting. This can be\u0000followed by a variance-decomposition based global sensitivity analysis. If\u0000needed, complex parameter distributions can be described, evaluated, and\u0000sampled from, with the help of Vine-copulas that are available in R. This\u0000approach is especially useful when new experimental data become available, and\u0000a previously calibrated model needs to be updated. Implementation: R is a high-level language and allows the use of\u0000sophisticated statistical methods. The ode solver we used is written in C\u0000(gsl_odeiv2, interface to R is ours). We use the SBtab tabular format for the\u0000model description, as well as the data and an event system to be able to model\u0000inputs frequently encountered in systems biology and neuroscience. The code has\u0000been tested on one node with 256 cores of a computing cluster, but smaller\u0000examples are included in the repository that can be run on a laptop. Source code: https://github.com/icpm-kth/uqsa","PeriodicalId":501170,"journal":{"name":"arXiv - QuanBio - Subcellular Processes","volume":"58 39","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138510943","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}
引用次数: 0
Strategies for targeting chondrosarcomas in vivo and molecular dissection of oncogenic events in chondrosarcomas: is epigenetics the culprit? 体内靶向软骨肉瘤的策略和软骨肉瘤致癌事件的分子解剖:表观遗传学是罪魁祸首吗?
arXiv - QuanBio - Subcellular Processes Pub Date : 2023-07-30 DOI: arxiv-2307.16231
Rédoane Daoudi
{"title":"Strategies for targeting chondrosarcomas in vivo and molecular dissection of oncogenic events in chondrosarcomas: is epigenetics the culprit?","authors":"Rédoane Daoudi","doi":"arxiv-2307.16231","DOIUrl":"https://doi.org/arxiv-2307.16231","url":null,"abstract":"It is obvious that both epigenetic and non-epigenetic actors contribute to\u0000tumorigenesis in chondrosarcomas and more generally in other cancers. Thus, the\u0000main altered pathways in chondrosarcomas are now well established and include\u0000both epigenetic and non-epigenetic pathways such as the PI3K-AKT signaling,\u0000EGFR overexpression, SPARC overexpression, c-myc overexpression, IHH/GLI1 axis,\u0000loss of Rb function, HIF1-alpha stabilization, IDH1 mutations, hypermethylation\u0000and SIRT1. This review aims to provide a detailed analysis of these pathways\u0000and highlights recurrent interactions between non-epigenetic and epigenetic\u0000actors in chondrosarcomas, raising the intriguing possibility of developing\u0000therapeutics targeting both epigenetic and non-epigenetic actors and supporting\u0000data from previous studies. Finally, we propose some strategies for targeting\u0000chondrosarcomas in vivo based on properties of this tumor.","PeriodicalId":501170,"journal":{"name":"arXiv - QuanBio - Subcellular Processes","volume":"58 40","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138510942","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}
引用次数: 0
Unravelling the fluorescence kinetics of light-harvesting proteins with simulated measurements 用模拟测量揭示光捕获蛋白的荧光动力学
arXiv - QuanBio - Subcellular Processes Pub Date : 2023-07-26 DOI: arxiv-2307.14043
Callum Gray, Lekshmi Kailas, Peter G. Adams, Christopher D. P. Duffy
{"title":"Unravelling the fluorescence kinetics of light-harvesting proteins with simulated measurements","authors":"Callum Gray, Lekshmi Kailas, Peter G. Adams, Christopher D. P. Duffy","doi":"arxiv-2307.14043","DOIUrl":"https://doi.org/arxiv-2307.14043","url":null,"abstract":"The plant light-harvesting pigment-protein complex LHCII is the major antenna\u0000sub-unit of PSII and is generally (though not universally) accepted to play a\u0000role in photoprotective energy dissipation under high light conditions, a\u0000process known Non-Photochemical Quenching (NPQ). The underlying mechanisms of\u0000energy trapping and dissipation within LHCII are still debated. Various\u0000proposed models differ considerably in their molecular and kinetic detail, but\u0000are often based on different interpretations of very similar transient\u0000absorption measurements of isolated complexes. Here we present a simulated\u0000measurement of the fluorescence decay kinetics of quenched LHCII aggregates to\u0000determine whether this relatively simple measurement can discriminate between\u0000different potential NPQ mechanisms. We simulate not just the underlying physics\u0000(excitation, energy migration, quenching and singlet-singlet annihilation) but\u0000also the signal detection and typical experimental data analysis. Comparing\u0000this to a selection of published fluorescence decay kinetics we find that: (1)\u0000Different proposed quenching mechanisms produce noticeably different\u0000fluorescence kinetics even at low (annihilation free) excitation density,\u0000though the degree of difference is dependent on pulse width. (2) Measured decay\u0000kinetics are consistent with most LHCII trimers becoming relatively slow\u0000excitation quenchers. A small sub-population of very fast quenchers produces\u0000kinetics which do not resemble any observed measurement. (3) It is necessary to\u0000consider at least two distinct quenching mechanisms in order to accurately\u0000reproduce experimental kinetics, supporting the idea that NPQ is not a simple\u0000binary switch switch.","PeriodicalId":501170,"journal":{"name":"arXiv - QuanBio - Subcellular Processes","volume":"58 34","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138510946","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}
引用次数: 0
Involvement of calcium channels Orai3 in the chemoresistance to cisplatin in non-small cell lung cancer (NSCLC) 钙通道Orai3参与非小细胞肺癌(NSCLC)顺铂化疗耐药
arXiv - QuanBio - Subcellular Processes Pub Date : 2023-07-18 DOI: arxiv-2307.10289
Rédoane Daoudi
{"title":"Involvement of calcium channels Orai3 in the chemoresistance to cisplatin in non-small cell lung cancer (NSCLC)","authors":"Rédoane Daoudi","doi":"arxiv-2307.10289","DOIUrl":"https://doi.org/arxiv-2307.10289","url":null,"abstract":"This is the second part of the previous review. In the previous review we\u0000suspected that Orai3 channels were involved in lung cancer and more precisely\u0000in several cancers. Here we confirm that calcium dysregulation is important for\u0000cancer development. in this paper we show that Orai3 is an upstream activator\u0000of AKT and we prove that AKT is involved in chemoresistance in NSCLC.","PeriodicalId":501170,"journal":{"name":"arXiv - QuanBio - Subcellular Processes","volume":"58 52","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138510842","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}
引用次数: 0
High-density single-molecule maps reveal transient membrane receptor interactions within a dynamically varying environment 高密度单分子图揭示瞬态膜受体相互作用在动态变化的环境
arXiv - QuanBio - Subcellular Processes Pub Date : 2023-07-14 DOI: arxiv-2307.07334
Nicolas Mateos, Parijat Sil, Sankarshan Talluri, Carlo Manzo, Satyajit Mayor, Maria Garcia-Parajo
{"title":"High-density single-molecule maps reveal transient membrane receptor interactions within a dynamically varying environment","authors":"Nicolas Mateos, Parijat Sil, Sankarshan Talluri, Carlo Manzo, Satyajit Mayor, Maria Garcia-Parajo","doi":"arxiv-2307.07334","DOIUrl":"https://doi.org/arxiv-2307.07334","url":null,"abstract":"Over recent years, super-resolution and single-molecule imaging methods have\u0000delivered unprecedented details on the nanoscale organization and dynamics of\u0000individual molecules in different contexts. Yet, visualizing single-molecule\u0000processes in living cells with the required spatial and temporal resolution\u0000remains highly challenging. Here, we report on an analytical approach that\u0000extracts such information from live-cell single-molecule imaging at\u0000high-labeling densities using standard fluorescence probes. Our\u0000high-density-mapping (HiDenMap) methodology provides single-molecule nanometric\u0000localization accuracy together with millisecond temporal resolution over\u0000extended observation times, delivering multi-scale spatiotemporal data that\u0000report on the interaction of individual molecules with their dynamic\u0000environment. We validated HiDenMaps by simulations of Brownian trajectories in\u0000the presence of patterns that restrict free diffusion with different\u0000probabilities. We further generated and analyzed HiDenMaps from single-molecule\u0000images of transmembrane proteins having different interaction strengths to\u0000cortical actin, including the transmembrane receptor CD44. HiDenMaps uncovered\u0000a highly heterogenous and multi-scale spatiotemporal organization for all the\u0000proteins that interact with the actin cytoskeleton. Notably, CD44 alternated\u0000between periods of random diffusion and transient trapping, likely resulting\u0000from actin-dependent CD44 nanoclustering. Whereas receptor trapping was dynamic\u0000and lasted for hundreds of milliseconds, actin remodeling occurred at the\u0000timescale of tens of seconds, coordinating the assembly and disassembly of CD44\u0000nanoclusters rich regions. Together, our data demonstrate the power of\u0000HiDenMaps to explore how individual molecules interact with and are organized\u0000by their environment in a dynamic fashion.","PeriodicalId":501170,"journal":{"name":"arXiv - QuanBio - Subcellular Processes","volume":"58 38","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138510944","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}
引用次数: 0
Understanding AKT-mediated chemoresistance: the relationship between ion channels and AKT activation 了解AKT介导的化学耐药:离子通道与AKT激活之间的关系
arXiv - QuanBio - Subcellular Processes Pub Date : 2023-07-13 DOI: arxiv-2307.07427
Rédoane Daoudi
{"title":"Understanding AKT-mediated chemoresistance: the relationship between ion channels and AKT activation","authors":"Rédoane Daoudi","doi":"arxiv-2307.07427","DOIUrl":"https://doi.org/arxiv-2307.07427","url":null,"abstract":"Overcoming chemoresistance is a challenge for multiple chemotherapeutics\u0000agents like cisplatin. ABC transporters such as MDR1 or MRPs and PI3K/AKT\u0000pathway have been proposed as actors of chemoresistance in several cancers. In\u0000this review we describe two downstream targets of Akt: c-myc and p53 in the\u0000chemoresistance. We suggest a potential link between p53, c-myc and ABC\u0000transporters expression. Consequently a link between Akt and ABC\u0000transporters-mediated chemoresistance may exist. Finally we show that Akt\u0000activation may be Orai-dependent and/or TRPC-dependent, suggesting that these\u0000ion channels could constitute a therapeutic target in cancer.","PeriodicalId":501170,"journal":{"name":"arXiv - QuanBio - Subcellular Processes","volume":"51 47","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138511047","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}
引用次数: 0
Charting the landscape of stochastic gene expression models using queueing theory 利用排队理论绘制随机基因表达模型的图景
arXiv - QuanBio - Subcellular Processes Pub Date : 2023-07-06 DOI: arxiv-2307.03253
Juraj Szavits-Nossan, Ramon Grima
{"title":"Charting the landscape of stochastic gene expression models using queueing theory","authors":"Juraj Szavits-Nossan, Ramon Grima","doi":"arxiv-2307.03253","DOIUrl":"https://doi.org/arxiv-2307.03253","url":null,"abstract":"Stochastic models of gene expression are typically formulated using the\u0000chemical master equation, which can be solved exactly or approximately using a\u0000repertoire of analytical methods. Here, we provide a tutorial review of an\u0000alternative approach based on queuing theory that has rarely been used in the\u0000literature of gene expression. We discuss the interpretation of six types of\u0000infinite server queues from the angle of stochastic single-cell biology and\u0000provide analytical expressions for the stationary and non-stationary\u0000distributions and/or moments of mRNA/protein numbers, and bounds on the Fano\u0000factor. This approach may enable the solution of complex models which have\u0000hitherto evaded analytical solution.","PeriodicalId":501170,"journal":{"name":"arXiv - QuanBio - Subcellular Processes","volume":"58 31","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138511031","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}
引用次数: 0
Membrane Thickness Sensitivity of Avian Prestin: Implications 禽Prestin膜厚度敏感性:意义
arXiv - QuanBio - Subcellular Processes Pub Date : 2023-07-05 DOI: arxiv-2307.02440
Kuni H Iwasa
{"title":"Membrane Thickness Sensitivity of Avian Prestin: Implications","authors":"Kuni H Iwasa","doi":"arxiv-2307.02440","DOIUrl":"https://doi.org/arxiv-2307.02440","url":null,"abstract":"Avian prestin is sensitive to membrane thickness as much as mammalian\u0000prestin, which undergoes conformational transitions in membrane area and\u0000thereby drives length changes of the cylindrical cell body of outer hair cells.\u0000The membrane thickness dependence of mammalian prestin stems from changes in\u0000hydrophobic profile in conformational states, accompanied by changes in their\u0000membrane area. Even though such area changes are not detected for avian\u0000prestin, it nonetheless bends hair bundles of avian short hair cells. Here it\u0000is suggested that the motile function of avian prestin can be based on\u0000conformational transitions involving shearing deformation of the membrane\u0000protein, which also leads to membrane thickness sensitivity.","PeriodicalId":501170,"journal":{"name":"arXiv - QuanBio - Subcellular Processes","volume":"58 51","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138510843","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}
引用次数: 0
Modelling cargo transport in crowded environments: effect of motor association to cargos 拥挤环境下的货物运输建模:机动关联对货物的影响
arXiv - QuanBio - Subcellular Processes Pub Date : 2023-07-03 DOI: arxiv-2307.00778
Sutapa Mukherji, Dhruvi K. Patel
{"title":"Modelling cargo transport in crowded environments: effect of motor association to cargos","authors":"Sutapa Mukherji, Dhruvi K. Patel","doi":"arxiv-2307.00778","DOIUrl":"https://doi.org/arxiv-2307.00778","url":null,"abstract":"In intracellular transports, motor proteins transport macromolecules as\u0000cargos to desired locations by moving on biopolymers such as microtubules.\u0000Recent experiments suggest that cargos that can associate motor proteins during\u0000their translocation have larger run-length, association time and can overcome\u0000the motor traffic on microtubule tracks. Here, we model the dynamics of a cargo\u0000that can associate at the most m free motors present on the track as obstacles\u0000to its motion. The proposed models display competing effects of association and\u0000crowding, leading to a peak in the run-length with the free motor density. This\u0000result is consistent with past experimental observations. For m=2 and 3, we\u0000show that this feature is governed by the largest eigenvalue of the transition\u0000matrix describing the cargo dynamics. In all the above cases, free motors are\u0000assumed to be present as stalled obstacles. We finally compare simulation\u0000results for the run-length for general scenarios where the free motors undergo\u0000processive motion in addition to binding and unbinding to or from the\u0000microtubule.","PeriodicalId":501170,"journal":{"name":"arXiv - QuanBio - Subcellular Processes","volume":"52 15","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138511045","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}
引用次数: 0
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