arXiv - QuanBio - Subcellular Processes最新文献

{"title":"Infer metabolic directions and magnitudes from moment differences of mass-weighted intensity distributions","authors":"Tuobang Li","doi":"arxiv-2402.14887","DOIUrl":"https://doi.org/arxiv-2402.14887","url":null,"abstract":"Metabolic pathways are fundamental maps in biochemistry that detail how\u0000molecules are transformed through various reactions. Metabolomics refers to the\u0000large-scale study of small molecules. High-throughput, untargeted, mass\u0000spectrometry-based metabolomics experiments typically depend on libraries for\u0000structural annotation, which is necessary for pathway analysis. However, only a\u0000small fraction of spectra can be matched to known structures in these libraries\u0000and only a portion of annotated metabolites can be associated with specific\u0000pathways, considering that numerous pathways are yet to be discovered. The\u0000complexity of metabolic pathways, where a single compound can play a part in\u0000multiple pathways, poses an additional challenge. This study introduces a\u0000different concept: mass-weighted intensity distribution, which is the empirical\u0000distribution of the intensities times their associated m/z values. Analysis of\u0000COVID-19 and mouse brain datasets shows that by estimating the differences of\u0000the point estimations of these distributions, it becomes possible to infer the\u0000metabolic directions and magnitudes without requiring knowledge of the exact\u0000chemical structures of these compounds and their related pathways. The overall\u0000metabolic momentum map, named as momentome, has the potential to bypass the\u0000current bottleneck and provide fresh insights into metabolomics studies. This\u0000brief report thus provides a mathematical framing for a classic biological\u0000concept.","PeriodicalId":501170,"journal":{"name":"arXiv - QuanBio - Subcellular Processes","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139980649","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":"Relaxation and noise-driven oscillations in a model of mitotic spindle dynamics","authors":"Dionn Hargreaves, Sarah Woolner, Oliver E. Jensen","doi":"arxiv-2402.10638","DOIUrl":"https://doi.org/arxiv-2402.10638","url":null,"abstract":"During cell division, the mitotic spindle moves dynamically through the cell\u0000to position the chromosomes and determine the ultimate spatial position of the\u0000two daughter cells. These movements have been attributed to the action of\u0000cortical force generators which pull on the astral microtubules to position the\u0000spindle, as well as pushing events by these same microtubules against the cell\u0000cortex and membrane. Attachment and detachment of cortical force generators\u0000working antagonistically against centring forces of microtubules have been\u0000modelled previously (Grill et al. 2005, Phys. Rev. Lett. 94:108104) via\u0000stochastic simulations and Fokker-Planck equations to predict oscillations of a\u0000spindle pole in one spatial dimension. Using systematic asymptotic methods, we\u0000reduce the Fokker-Planck system to a set of ordinary differential equations\u0000(ODEs), consistent with a set proposed by Grill et al., which provide accurate\u0000predictions of the conditions for the Fokker-Planck system to exhibit\u0000oscillations. In the limit of small restoring forces, we derive an algebraic\u0000prediction of the amplitude of spindle-pole oscillations and demonstrate the\u0000relaxation structure of nonlinear oscillations. We also show how noise-induced\u0000oscillations can arise in stochastic simulations for conditions in which the\u0000Fokker-Planck system predicts stability, but for which the period can be\u0000estimated directly by the ODE model.","PeriodicalId":501170,"journal":{"name":"arXiv - QuanBio - Subcellular Processes","volume":"9 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139902044","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":"Advecting Scaffolds: Controlling The Remodelling Of Actomyosin With Anillin","authors":"Denni Currin-RossCentre for Cell Biology of Chronic Disease, Institute for Molecular Bioscience, The University of Queensland, AustraliaSchool of Physics, UNSW, AustraliaEMBL Australia Node in Single Molecule Science, School of Biomedical Sciences, UNSW, Australia, Sami C. Al-IzziDepartment of Mathematics, Faculty of Mathematics and Natural Sciences, University of Oslo, Norway, Ivar NoordstraCentre for Cell Biology of Chronic Disease, Institute for Molecular Bioscience, The University of Queensland, Australia, Alpha S. YapCentre for Cell Biology of Chronic Disease, Institute for Molecular Bioscience, The University of Queensland, Australia, Richard G. MorrisSchool of Physics, UNSW, AustraliaEMBL Australia Node in Single Molecule Science, School of Biomedical Sciences, UNSW, Australia","doi":"arxiv-2402.07430","DOIUrl":"https://doi.org/arxiv-2402.07430","url":null,"abstract":"We propose and analyse an active hydrodynamic theory that characterises the\u0000effects of the scaffold protein anillin. Anillin is found at major sites of\u0000cortical activity, such as adherens junctions and the cytokinetic furrow, where\u0000the canonical regulator of actomyosin remodelling is the small GTPase, RhoA.\u0000RhoA acts via intermediary 'effectors' to increase both the rates of activation\u0000of myosin motors and the polymerisation of actin filaments. Anillin has been\u0000shown to scaffold this action of RhoA - improving critical rates in the\u0000signalling pathway without altering the essential biochemistry - but its\u0000contribution to the wider spatio-temporal organisation of the cortical\u0000cytoskeleton remains poorly understood. Here, we combine analytics and numerics\u0000to show how anillin can non-trivially regulate the cytoskeleton at hydrodynamic\u0000scales. At short times, anillin can amplify or dampen existing contractile\u0000instabilities, as well as alter the parameter ranges over which they occur. At\u0000long times, it can change both the size and speed of steady-state travelling\u0000pulses. The primary mechanism that underpins these behaviours is established to\u0000be the advection of anillin by myosin II motors, with the specifics relying on\u0000the values of two coupling parameters. These codify anillin's effect on local\u0000signalling kinetics and can be traced back to its interaction with the acidic\u0000phospholipid phosphatidylinositol 4,5-bisphosphate (PIP2), thereby establishing\u0000a putative connection between actomyosin remodelling and membrane composition.","PeriodicalId":501170,"journal":{"name":"arXiv - QuanBio - Subcellular Processes","volume":"55 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139759511","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":"Immunogenic cell death triggered by pathogen ligands via host germ line-encoded receptors","authors":"Chuang Li, Yichen Wei, Chao Qin, Shifan Chen, Xiaolong Shao","doi":"arxiv-2402.04422","DOIUrl":"https://doi.org/arxiv-2402.04422","url":null,"abstract":"The strategic induction of cell death serves as a crucial immune defense\u0000mechanism for the eradication of pathogenic infections within host cells.\u0000Investigating the molecular mechanisms underlying immunogenic cell pathways has\u0000significantly enhanced our understanding of the host's immunity. This review\u0000provides a comprehensive overview of the immunogenic cell death mechanisms\u0000triggered by pathogen infections, focusing on the critical role of pattern\u0000recognition receptors. In response to infections, host cells dictate a variety\u0000of cell death pathways, including apoptosis, pyroptosis, necrosis, and\u0000lysosomal cell death, which are essential for amplifying immune responses and\u0000controlling pathogen dissemination. Key components of these mechanisms are host\u0000cellular receptors that recognize pathogen-associated ligands. These receptors\u0000activate downstream signaling cascades, leading to the expression of\u0000immunoregulatory genes and the production of antimicrobial cytokines and\u0000chemokines. Particularly, the inflammasome, a multi-protein complex, plays a\u0000pivotal role in these responses by processing pro-inflammatory cytokines and\u0000inducing pyroptotic cell death. Pathogens, in turn, have evolved strategies to\u0000manipulate these cell death pathways, either by inhibiting them to facilitate\u0000their replication or by triggering them to evade host defenses. This dynamic\u0000interplay between host immune mechanisms and pathogen strategies highlights the\u0000intricate co-evolution of microbial virulence and host immunity.","PeriodicalId":501170,"journal":{"name":"arXiv - QuanBio - Subcellular Processes","volume":"16 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139759282","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":"Geometry controls diffusive target encounters and escape in tubular structures","authors":"Junyeong L. Kim, Aidan I. Brown","doi":"arxiv-2402.03059","DOIUrl":"https://doi.org/arxiv-2402.03059","url":null,"abstract":"The endoplasmic reticulum (ER) is a network of sheet-like and tubular\u0000structures that spans much of a cell and contains molecules undergoing\u0000diffusive searches for targets, such as unfolded proteins searching for\u0000chaperones and recently-folded proteins searching for export sites. By applying\u0000a Brownian dynamics algorithm to simulate molecule diffusion, we describe how\u0000ER tube geometry influences whether a searcher will encounter a nearby target\u0000or instead diffuse away to a region near to a distinct target, as well as the\u0000timescale of successful searches. We find that targets are more likely to be\u0000found for longer and narrower tubes, and larger targets, and that search in the\u0000tube volume is more sensitive to the search geometry compared to search on the\u0000tube surface. Our results suggest ER proteins searching for low-density targets\u0000in the membrane and the lumen are very likely to encounter the nearest target\u0000before diffusing to the vicinity of another target. Our results have\u0000implications for the design of target search simulations and calculations and\u0000interpretation of molecular trajectories on the ER network, as well as other\u0000organelles with tubular geometry.","PeriodicalId":501170,"journal":{"name":"arXiv - QuanBio - Subcellular Processes","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139759274","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":"Analysis of a detailed multi-stage model of stochastic gene expression using queueing theory and model reduction","authors":"Muhan Ma, Juraj Szavits-Nossan, Abhyudai Singh, Ramon Grima","doi":"arxiv-2401.12661","DOIUrl":"https://doi.org/arxiv-2401.12661","url":null,"abstract":"We introduce a biologically detailed, stochastic model of gene expression\u0000describing the multiple rate-limiting steps of transcription, nuclear pre-mRNA\u0000processing, nuclear mRNA export, cytoplasmic mRNA degradation and translation\u0000of mRNA into protein. The processes in sub-cellular compartments are described\u0000by an arbitrary number of processing stages, thus accounting for a\u0000significantly finer molecular description of gene expression than conventional\u0000models such as the telegraph, two-stage and three-stage models of gene\u0000expression. We use two distinct tools, queueing theory and model reduction\u0000using the slow-scale linear-noise approximation, to derive exact or approximate\u0000analytic expressions for the moments or distributions of nuclear mRNA,\u0000cytoplasmic mRNA and protein fluctuations, as well as lower bounds for their\u0000Fano factors in steady-state conditions. We use these to study the phase\u0000diagram of the stochastic model; in particular we derive parametric conditions\u0000determining three types of transitions in the properties of mRNA fluctuations:\u0000from sub-Poissonian to super-Poissonian noise, from high noise in the nucleus\u0000to high noise in the cytoplasm, and from a monotonic increase to a monotonic\u0000decrease of the Fano factor with the number of processing stages. In contrast,\u0000protein fluctuations are always super-Poissonian and show weak dependence on\u0000the number of mRNA processing stages. Our results delineate the region of\u0000parameter space where conventional models give qualitatively incorrect results\u0000and provide insight into how the number of processing stages, e.g. the number\u0000of rate-limiting steps in initiation, splicing and mRNA degradation, shape\u0000stochastic gene expression by modulation of molecular memory.","PeriodicalId":501170,"journal":{"name":"arXiv - QuanBio - Subcellular Processes","volume":"18 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139557438","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":"Target search in the CRISPR/Cas9 system: Facilitated diffusion with target cues","authors":"Qiao Lu, Simone Pigolotti","doi":"arxiv-2401.05714","DOIUrl":"https://doi.org/arxiv-2401.05714","url":null,"abstract":"We study how Cas9, a central component of the CRISPR/Cas9 system, searches\u0000for a target sequence on the DNA. We propose a model that includes as key\u0000ingredients 3D diffusion, 1D sliding along the DNA, and the effect of short\u0000binding sequences preceding the target (protospacer adjacent sequences --\u0000PAMs). This latter aspect constitutes the main difference with traditional\u0000facilitated diffusion of transcription factors. We solve our model, obtaining\u0000an expression for the average search time of Cas9 for its target. We find that\u0000experimentally measured kinetic parameters are close to the values yielding an\u0000optimal search time. Our results rationalize the role of PAMs in guiding the\u0000search process, and show that Cas9 searches for its targets in a nearly optimal\u0000way.","PeriodicalId":501170,"journal":{"name":"arXiv - QuanBio - Subcellular Processes","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139458844","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":"Optimal control of ribosome population for gene expression under periodic nutrient intake","authors":"Clément Soubrier, Eric Foxall, Luca Ciandrini, Khanh Dao Duc","doi":"arxiv-2401.06294","DOIUrl":"https://doi.org/arxiv-2401.06294","url":null,"abstract":"Translation of proteins is a fundamental part of gene expression that is\u0000mediated by ribosomes. As ribosomes significantly contribute to both cellular\u0000mass and energy consumption, achieving efficient management of the ribosome\u0000population is also crucial to metabolism and growth. Inspired by biological\u0000evidence for nutrient-dependent mechanisms that control both ribosome active\u0000degradation and genesis, we introduce a dynamical model of protein production,\u0000that includes the dynamics of resources and control over the ribosome\u0000population. Under the hypothesis that active degradation and biogenesis are\u0000optimal for maximizing and maintaining protein production, we aim to\u0000qualitatively reproduce empirical observations of the ribosome population\u0000dynamics. Upon formulating the associated optimization problem, we first\u0000analytically study the stability and global behaviour of solutions under\u0000constant resource input, and characterize the extent of oscillations and\u0000convergence rate to a global equilibrium. We further use these results to\u0000simplify and solve the problem under a quasi-static approximation. Using\u0000biophysical parameter values, we find that optimal control solutions lead to\u0000both control mechanisms and the ribosome population switching between periods\u0000of feeding and fasting, suggesting that the intense regulation of ribosome\u0000population observed in experiments allows to maximize and maintain protein\u0000production. Finally, we find some range for the control values over which such\u0000a regime can be observed, depending on the intensity of fasting.","PeriodicalId":501170,"journal":{"name":"arXiv - QuanBio - Subcellular Processes","volume":"35 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139470214","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":"Redox Poise during Rhodospirillum rubrum Phototrophic Growth Drives Large-scale Changes in Macromolecular Synthesis Pathways","authors":"William R. Cannon, Ethan King, Katherine A. Huening, Justin A. North","doi":"arxiv-2401.04862","DOIUrl":"https://doi.org/arxiv-2401.04862","url":null,"abstract":"During photoheterotrophic growth on organic substrates, purple nonsulfur\u0000photosynthetic bacteria like Rhodospirillum rubrum can acquire electrons by\u0000multiple means, including oxidation of organic substrates, oxidation of\u0000inorganic electron donors (e.g. H$_2$), and by reverse electron flow from the\u0000photosynthetic electron transport chain. These electrons are stored in the form\u0000of reduced electron-carrying cofactors (e.g. NAD(P)H and ferredoxin). The ratio\u0000of oxidized to reduced redox cofactors (e.g. ratio of NAD(P)+:NAD(P)H), or\u0000'redox poise` is difficult to understand or predict, as are the the cellular\u0000processes for dissipating these reducing equivalents. Using physics-based\u0000models that capture mass action kinetics consistent with the thermodynamics of\u0000reactions and pathways, a range of redox conditions for heterophototrophic\u0000growth are evaluated, from conditions in which the NADP+/NADPH levels\u0000approached thermodynamic equilibrium to conditions in which the NADP+/NADPH\u0000ratio is far above the typical physiological values. Modeling results together\u0000with experimental measurements of macro molecule levels (DNA, RNA, proteins and\u0000fatty acids) indicate that the redox poise of the cell results in large-scale\u0000changes in the activity of biosynthetic pathways. Phototrophic growth is less\u0000coupled than expected to producing reductant, NAD(P)H, by reverse electron flow\u0000from the quinone pool. Instead, it primarily functions for ATP production\u0000(photophosphorylation), which drives reduction even when NADPH levels are\u0000relatively low compared to NADP+. The model, in agreement with experimental\u0000measurements of macromolecule ratios of cells growing on different carbon\u0000substrates, indicate that the dynamics of nucleotide versus lipid and protein\u0000production is likely a significant mechanism of balancing oxidation and\u0000reduction in the cell.","PeriodicalId":501170,"journal":{"name":"arXiv - QuanBio - Subcellular Processes","volume":"30 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139421119","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":"Beyond Michaelis-Menten: Allosteric Rate Control of Chaos","authors":"Tjeerd V. olde Scheper","doi":"arxiv-2401.04786","DOIUrl":"https://doi.org/arxiv-2401.04786","url":null,"abstract":"The method developed by Michaelis and Menten was foundational in the\u0000development of our understanding of biochemical reaction kinetics. Extended\u0000models of metabolism encapsulated by reaction rate theory, stochastic reaction\u0000models, and dynamic flux estimation, amongst others, address aspects of this\u0000fundamental idea. The limitations of these approaches are well understood, and\u0000efforts to overcome those issues so far have been plentiful but with limited\u0000success. The known issues can be summarised as the sole dependent relation with\u0000substrate concentration, the encapsulation of rate in a single relevant scalar,\u0000and the subsequent lack of functional control that results from this\u0000assumption. The Rate Control of Chaos (RCC) is a nonlinear control method that\u0000has been shown to be effective in controlling the dynamic state of biological\u0000oscillators based on the concept of rate limitation of the exponential growth\u0000in chaotic systems. Extending RCC with allosteric properties allows robust\u0000control of the enzymatic process, and replicates the Michaelis-Menten kinetics.\u0000The emergent dynamics is robust to perturbations and noise but susceptible to\u0000regulatory adjustments. This control method adapts the control parameters\u0000dynamically in the presence of a ligand, and permits introduction of energy\u0000relations into the control function. The dynamic nature of the control\u0000eliminates the steady-state requirements and allows the modelling of\u0000large-scale dynamic behaviour, potentially addressing issues in metabolic\u0000disorder and failure of metabolic control.","PeriodicalId":501170,"journal":{"name":"arXiv - QuanBio - Subcellular Processes","volume":"9 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139422653","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}