Searcharxiv⌕ Search

SEARCH · Searcharxiv

Results for “q-bio.SC”

Search indexed arXiv papers on artificial intelligence, large language models, computer vision and robotics. Read source abstracts and follow links to arXiv.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 73 records · Page 4Linked to original sources
arXiv2008

A quantitative comparison of sRNA-based and protein-based gene regulation

Small, non-coding RNAs (sRNAs) play important roles as genetic regulators in prokaryotes. sRNAs act post-transcriptionally via complementary pairing with target mRNAs to regulate protein expression. We use a quantitative approach to compare and contrast sRNAs with conventional transcription factors (TFs) to better understand the advantages of each form of regulation. In particular, we calculate the steady-state behavior, noise properties, frequency-dependent gain (amplification), and dynamical response to large input signals of both forms of regulation. While the mean steady-state behavior of sRNA-regulated proteins exhibits a distinctive tunable threshold-linear behavior, our analysis shows that transcriptional bursting leads to significantly higher intrinsic noise in sRNA-based regulation than in TF-based regulation in a large range of expression levels and limits the ability of sRNAs to perform quantitative signaling. Nonetheless, we find that sRNAs are better than TFs at filtering noise in input signals. Additionally, we find that sRNAs allow cells to respond rapidly to large changes in input signals. These features suggest a niche for sRNAs in allowing cells to transition quickly yet reliably between distinct states. This functional niche is consistent with the widespread appearance of sRNAs in stress-response and quasi-developmental networks in prokaryotes.

q-bio.MN↗
arXiv2008

The influence of microwave radiation on the state of chromatin in human cells

Isolated human buccal epithelium cell were irradiated by microwaves at frequency f=35 GHz and surface power density E=30 mcW/cm2. The state of chromatin in human cells was determined by methodsof light and electron microscopy. The state of cell membranes was evaluated by the method of vital indigo carmine staining. The microwave-induced condensation of chromatin in human cells was revealed. Left side circulary polarized waves induced less effect than linearly polarized radiation. The linearly polarized electromagnetic waves induced cell membrane damage revealed by the increase of cell stainability. The data obtained are discussed in connection with the mechanisms of biologica effect of electromagnetic waves.

q-bio.MN↗
arXiv2009

Investigating the two-moment characterisation of subcellular biochemical networks

While ordinary differential equations (ODEs) form the conceptual framework for modelling many cellular processes, specific situations demand stochastic models to capture the influence of noise. The most common formulation of stochastic models for biochemical networks is the chemical master equation (CME). While stochastic simulations are a practical way to realise the CME, analytical approximations offer more insight into the influence of noise. Towards that end, the two-moment approximation (2MA) is a promising addition to the established analytical approaches including the chemical Langevin equation (CLE) and the related linear noise approximation (LNA). The 2MA approach directly tracks the mean and (co)variance which are coupled in general. This coupling is not obvious in CME and CLE and ignored by LNA and conventional ODE models. We extend previous derivations of 2MA by allowing a) non-elementary reactions and b) relative concentrations. Often, several elementary reactions are approximated by a single step. Furthermore, practical situations often require the use relative concentrations. We investigate the applicability of the 2MA approach to the well established fission yeast cell cycle model. Our analytical model reproduces the clustering of cycle times observed in experiments. This is explained through multiple resettings of MPF, caused by the coupling between mean and (co)variance, near the G2/M transition.

q-bio.SC↗
arXiv2008

Target Location by DNA-Binding Proteins: Effects of Roadblocks and DNA Looping

The model of facilitated diffusion describes how DNA-binding proteins, such as transcription factors (TFs), find their chromosomal targets by combining 3D diffusion through the cytoplasm and 1D sliding along nonspecific DNA sequences. The redundant 1D diffusion near the specific binding site extends the target size and facilitates target location. While this model successfully predicts the kinetics measured in test tubes, it has not been extended to account for the highly crowded environment in living cells. Here, we investigate the effect of other DNA-binding proteins that partially occupy the bacterial chromosome. We show how they would slow down the search process, mainly through restricted sliding near the target. This implies that increasing the overall DNA-binding protein concentration would have a marginal effect in reducing the search time, because any additional proteins would restrict the search process for each other. While the presence of other proteins prevents sliding from the flanking DNA, DNA looping provides an alternative path to transfer from neighboring sites to the target efficiently. We propose that, when looping is faster than the initial search process, the auxiliary binding sites further extend the effective target region and therefore facilitate the target location.

q-bio.QM↗
arXiv2008

Ribosome collisions and Translation efficiency: Optimization by codon usage and mRNA destabilization

Individual mRNAs are translated by multiple ribosomes that initiate translation with a few seconds interval. The ribosome speed is codon dependant, and ribosome queuing has been suggested to explain specific data for translation of some mRNAs in vivo. By modelling the stochastic translation process as a traffic problem, we here analyze conditions and consequences of collisions and queuing. The model allowed us to determine the on-rate (0.8 to 1.1 initiations per sec) and the time (1 sec) the preceding ribosome occludes initiation for Escherichia coli lacZ mRNA in vivo. We find that ribosome collisions and queues are inevitable consequences of a stochastic translation mechanism that reduce the translation efficiency substantially on natural mRNAs. The cells minimize collisions by having its mRNAs being unstable and by a highly selected codon usage in the start of the mRNA. The cost of mRNA breakdown is offset by the concomitant increase in translational efficiency.

q-bio.SC↗
arXiv2008

A thermodynamic switch for chromosome colocalization

A general model for the early recognition and colocalization of homologous DNA sequences is proposed. We show, on a thermodynamic ground, how the distance between two homologous DNA sequences is spontaneously regulated by the concentration and affinity of diffusible mediators binding them, which act as a switch between two phases corresponding to independence or colocalization of pairing regions.

q-bio.SC↗
arXiv2008

Stochastic models and numerical algorithms for a class of regulatory gene networks

Regulatory gene networks contain generic modules like those involving feedback loops, which are essential for the regulation of many biological functions. We consider a class of self-regulated genes which are the building blocks of many regulatory gene networks, and study the steady state distributions of the associated Gillespie algorithm by providing efficient numerical algorithms. We also study a regulatory gene network of interest in synthetic biology and in gene therapy, using mean-field models with time delays. Convergence of the related time-nonhomogeneous Markov chain is established for a class of linear catalytic networks with feedback loops

q-bio.SC↗
arXiv2008

The switching dynamics of the bacterial flagellar motor

Many swimming bacteria are propelled by flagellar motors that stochastically switch between the clockwise and counterclockwise rotation direction. While the switching dynamics are one of the most important characteristics of flagellar motors, the mechanisms that control switching are poorly understood. We present a statistical-mechanical model of the flagellar rotary motor, which consists of a number of stator proteins that drive the rotation of a ring of rotor proteins, which in turn drives the rotation of a flagellar filament. At the heart of our model is the assumption that the rotor protein complex can exist in two conformational states corresponding to the two respective rotation directions, and that switching between these states depends on interactions with the stator proteins. This naturally couples the switching dynamics to the rotation dynamics, making the switch sensitive to torque and speed. Another key element of our model is that after a switching event, it takes time for the load to build up, due to polymorphic transitions of the filament. Our model predicts that this slow relaxation dynamics of the filament, in combination with the load dependence of the switching frequency, leads to a characteristic switching time, in agreement with recent observations.

q-bio.SC↗
arXiv2008

Tumor suppressor and anti-inflammatory protein: an expanded view on insulin-degrading enzyme (IDE)

In 1994, I conjectured that insulin-degrading enzyme (IDE) acts as an inhibitor of malignant transformation by degrading insulin and thus preventing this major growth-stimulatory hormone from binding and thereby inactivating the retinoblastoma tumor suppressor protein (RB). Ten years later, I discovered that a carboxyterminal RB amino acid sequence resembles the catalytic center of IDE. This structural homology raised the possibility that insulin degradation is a basic mechanism for tumor suppression shared by RB and IDE. Subsequently, a first immunohistochemical study on the differential expression of human IDE in normal tissues, primary tumors and their corresponding lymph node metastases further corroborated the initial conjecture on IDE being an antineoplastic molecule. In this report, it is shown that IDE harbors ankyrin repeat-like amino acid sequences through which it might bind and, as a result, antagonize the pro-inflammatory factor NF-kappaB as well as cyclin-dependent kinases (CDKs). As equally revealed here, IDE also contains 2 RXL cyclin-binding motifs which could contribute to its presumed inhibition of CDKs. These new findings suggest that IDE is potentially able to suppress both inflammation and oncogenesis by several mechanisms that ultimately ensure RB function.

q-bio.BM↗
arXiv2009

Fundamentally different strategies for transcriptional regulation are revealed by information-theoretical analysis of binding motifs

To regulate a particular gene, a transcription factor (TF) needs to bind a specific genome location. How is this genome address specified amid the presence of ~10^6-10^9 decoy sites? Our analysis of 319 known TF binding motifs clearly demonstrates that prokaryotes and eukaryotes use strikingly different strategies to target TFs to specific genome locations; eukaryotic TFs exhibit widespread nonfunctional binding and require clustering of sites in regulatory regions for specificity.

q-bio.GN↗
arXiv2008

From random to directed motion: Understanding chemotaxis in E. Coli within a simplified model

The bacterium E.Coli swims in a zig-zag manner, in a series of straight runs and tumbles occurring alternately, with the run-durations dependent on the local spatial gradient of chemo-attractants/repellants. This enables the organism to move towards nutrient sources and move away from toxins. The signal transduction network of E.Coli has been well-characterized, and theoretical modeling has been used, with some success, in understanding its many remarkable features, including the near-perfect adaptation to spatially uniform stimulus. We study a reduced form of this network, with 3 methylation states for the receptor instead of 5. We derive an analytical form of the response function of the tumbling rate and use it to compute the drift velocity of the bacterium in the presence of a weak spatial attractant gradient.

q-bio.CB↗
arXiv2009

RNA polymerase motor on DNA track: effects of interactions, external force and torque

RNA polymerase (RNAP) is a mobile molecular workshop that polymerizes a RNA molecule by adding monomeric subunits one by one, while moving step by step on the DNA template itself. Here we develop a theoretical model by incorporating the steric interactions of the RNAPs and their mechanochemical cycles which explicitly captures the cyclical shape changes of each motor. Using this model, we explain not only the dependence of the average velocity of a RNAP on the externally applied load force, but also predict a {\it nonmotonic} variation of the average velocity on external torque. We also show the effect of steric interactions of the motors on the total rate of RNA synthesis. In principle, our predictions can be tested by carrying out {\it in-vitro} experiments which we suggest here.

physics.bio-ph↗
arXiv2008

A physical model of nicotinic ACh receptor kinetics

We present a new approach to nicotinic receptor kinetics and a new model explaining random variabilities in the duration of open events. The model gives new interpretation on brief and long receptor openings and predicts (for two identical binding sites) the presence of three components in the open time distribution: two brief and a long. We also present the physical model of the receptor block. This picture naturally and universally explains receptor desensitization, the phenomenon of central importance in cellular signaling. The model is based on single-channel experiments concerning the effects of hydrocortisone (HC) on the kinetics of control wild-type (WT) and mutated alphaD200Q mouse nicotinic acetylcholine receptors (nAChRs), expressed in HEK 293 cells. The appendix contains an original result from probability renewal theory: a derivation of the probability distribution function for the duration of a process performed by two independent servers.

q-bio.NC↗
arXiv2009

Bidirectional cooperative motion of myosin-II motors on actin tracks with randomly alternating polarities

The cooperative action of many molecular motors is essential for dynamic processes such as cell motility and mitosis. This action can be studied by using motility assays in which the motion of cytoskeletal filaments over a surface coated with motor proteins is tracked. In previous studies of actin-myosin II systems, fast directional motion was observed, reflecting the tendency of myosin II motors to propagate unidirectionally along actin filaments. Here, we present a motility assay with actin bundles consisting of short filamentous segments with randomly alternating polarities. These actin tracks exhibit bidirectional motion with macroscopically large time intervals (of the order of several seconds) between direction reversals. Analysis of this bidirectional motion reveals that the characteristic reversal time, $τ_{rev}$, does not depend on the size of the moving bundle or on the number of motors, $N$. This observation contradicts previous theoretical calculations based on a two-state ratchet model [Badoual et al., Proc. Natl. Acad. Sci. USA, vol. 99, p. 6696 (2002)], predicting an exponential increase of $τ_{rev}$ with $N$. We present a modified version of this model that takes into account the elastic energy due to the stretching of the actin track by the myosin II motors. The new model yields a very good quantitative agreement with the experimental results.

cond-mat.soft↗
arXiv2009

Dynamics of the bacterial flagellar motor with multiple stators - Supporting Information

In this supporting information we briefly describe the torque-speed measurement procedure. We show the hook spring compliance used in the simulations. We analyze the distribution functions of the moving and waiting time intervals. We study the dependence of the torque plateau region on the stator jumping rate and the cutoff angle, and the robustness of the results against different rotor-stator- potential and load-rotor forces.

q-bio.SC↗
arXiv2009

The role of cooperative binding on noise expression

The origin of stochastic fluctuations in gene expression has received considerable attention recently. Fluctuations in gene expression are particularly pronounced in cellular systems because of the small copy number of species undergoing transitions between discrete chemical states and the small size of biological compartments. In this paper, we propose a stochastic model for gene expression regulation including several binding sites, considering elementary reactions only. The model is used to investigate the role of cooperativity on the intrinsic fluctuations of gene expression, by means of master equation formalism. We found that the Hill coefficient and the level of noise increases as the interaction energy between activators increases. Additionally, we show that the model allows to distinguish between two cooperative binding mechanisms.

q-bio.SC↗
arXiv2009

Power Spectrum of Out-of-equilibrium Forces in Living Cells : Amplitude and Frequency Dependence

Living cells exhibit an important out-of-equilibrium mechanical activity, mainly due to the forces generated by molecular motors. These motor proteins, acting individually or collectively on the cytoskeleton, contribute to the violation of the fluctuation-dissipation theorem in living systems. In this work we probe the cytoskeletal out-of-equilibrium dynamics by performing simultaneous active and passive microrheology experiments, using the same micron-sized probe specifically bound to the actin cortex. The free motion of the probe exhibits a constrained, subdiffusive behavior at short time scales (t < 2s), and a directed, superdiffusive behavior at larger time scales, while, in response to a step force, its creep function presents the usual weak power law dependence with time. Combining the results of both experiments, we precisely measure for the first time the power spectrum of the force fluctuations exerted on this probe, which lies more than one order of magnitude above the spectrum expected at equilibrium, and greatly depends on frequency. We retrieve an effective temperature Teff of the system, as an estimate of the departure from thermal equilibrium. This departure is especially pronounced on long time scales, where Teff bears the footprint of the cooperative activity of motors pulling on the actin network. ATP depletion reduces the fluctuating force amplitude and results in a sharp decrease of Teff towards equilibrium.

physics.bio-ph↗