803 results on '"Chowdhury, Debashish"'
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2. The burden of headache disorders in North India: methodology, and validation of a Hindi version of the HARDSHIP questionnaire, for a community-based survey in Delhi and national capital territory region
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Duggal, Ashish, Chowdhury, Debashish, Krishnan, Anand, Amarchand, Ritvik, and Steiner, Timothy J.
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- 2024
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3. Coordination, cooperation, competition, crowding and congestion of molecular motors: Theoretical models and computer simulations
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Sen, Aritra, primary, Chowdhury, Debashish, additional, and Kunwar, Ambarish, additional
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- 2024
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4. Treatment in the emergency department
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Ling, Yu-Hsiang, primary, Chowdhury, Debashish, additional, and Wang, Shuu-Jiun, additional
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- 2024
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5. Eco-evolutionary games for harvesting self-renewing common resource: Effect of growing harvester population
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Bairagya, Joy Das, Mondal, Samrat Sohel, Chowdhury, Debashish, and Chakraborty, Sagar
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Quantitative Biology - Populations and Evolution ,Nonlinear Sciences - Adaptation and Self-Organizing Systems ,Physics - Biological Physics ,Physics - Physics and Society - Abstract
The tragedy of the commons (TOC) is a ubiquitous social dilemma witnessed in interactions between a population of living entities and shared resources available to them: The individuals in the population tend to selfishly overexploit a common resource as it is arguably the rational choice, or in case of non-human beings, it may be an evolutionarily uninvadable action. How to avert the TOC is a significant problem related to the conservation of resources. It is not hard to envisage situations where the resource could be self-renewing and the size of the population may be dependent on the state of the resource through the fractions of the population employing different exploitation rates. If the self-renewal rate of the resource lies between the maximum and the minimum exploitation rates, it is not a priori obvious under what conditions the TOC can be averted. In this paper, we address this question analytically and numerically using the setup of an evolutionary game theoretical replicator equation that models the Darwinian tenet of natural selection. Through the replicator equation, while we investigate how a population of replicators exploit the shared resource, the latter's dynamical feedback on the former is also not ignored. We also present a transparent bottom-up derivation of the game-resource feedback model to facilitate future studies on the stochastic effects on the findings presented herein., Comment: 10 pages, 3 figures
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- 2022
6. Length control of long cell protrusions: rulers, timers and transport
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Patra, Swayamshree, Chowdhury, Debashish, and Jülicher, Frank
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Physics - Biological Physics ,Condensed Matter - Statistical Mechanics ,Nonlinear Sciences - Adaptation and Self-Organizing Systems ,Quantitative Biology - Subcellular Processes - Abstract
A living cell uses long tubular appendages for locomotion and sensory purposes. Hence, assembling and maintaining a protrusion of correct length is crucial for its survival and overall performance. Usually the protrusions lack the machinery for the synthesis of building blocks and imports them from the cell body. What are the unique features of the transport logistics which facilitate the exchange of these building blocks between the cell and the protrusion? What kind of `rulers' and `timers' does the cell use for constructing its appendages of correct length on time? How do the multiple appendages coordinate and communicate among themselves during different stages of their existence? How frequently do the fluctuations drive the length of these dynamic protrusions out of the acceptable bounds? These questions are addressed from a broad perspective in this review which is organized in three parts. In part-I the list of all known cell protrusions is followed by a comprehensive list of the mechanisms of length control of cell protrusions reported in the literature. We review not only the dynamics of the genesis of the protrusions, but also their resorption and regrowth as well as regeneration after amputation. As a case study in part-II, the specific cell protrusion that has been discussed in detail is eukaryotic flagellum (also known as cilium); this choice was dictated by the fact that flagellar length control mechanisms have been studied most extensively over more than half a century in cells with two or more flagella. Although limited in scope, brief discussions on a few non-flagellar cell protrusions in part-III of this review is intended to provide a glimpse of the uncharted territories and challenging frontiers of research on subcellular length control phenomena that awaits vigorous investigations., Comment: Preprint of a Review Article; comments are welcome
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- 2022
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7. Game-environment feedback dynamics in growing population: Effect of finite carrying capacity
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Bairagya, Joy Das, Mondal, Samrat Sohel, Chowdhury, Debashish, and Chakraborty, Sagar
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Nonlinear Sciences - Adaptation and Self-Organizing Systems ,Physics - Biological Physics ,Quantitative Biology - Populations and Evolution - Abstract
The tragedy of the commons (TOC) is an unfortunate situation where a shared resource is exhausted due to uncontrolled exploitation by the selfish individuals of a population. Recently, the paradigmatic replicator equation has been used in conjunction with a phenomenological equation for the state of the shared resource to gain insight into the influence of the games on the TOC. The replicator equation, by construction, models a fixed infinite population undergoing microevolution. Thus, it is unable to capture any effect of the population growth and the carrying capacity of the population although the TOC is expected to be dependent on the size of the population. Therefore, in this paper, we present a mathematical framework that incorporates the density dependent payoffs and the logistic growth of the population in the eco-evolutionary dynamics modelling the game-resource feedback. We discover a bistability in the dynamics: a finite carrying capacity can either avert or cause the TOC depending on the initial states of the resource and the initial fraction of cooperators. In fact, depending on the type of strategic game-theoretic interaction, a finite carrying capacity can either avert or cause the TOC when it is exactly the opposite for the corresponding case with infinite carrying capacity., Comment: 12 pages, 5 figures, accepted in Physical Review E
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- 2021
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8. Flagellar length control in multiflagellated eukaryotes: a case study with Giardia
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Patra, Swayamshree and Chowdhury, Debashish
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Physics - Biological Physics - Abstract
Every organism has a size that is convenient for its function. Not only multicellular organisms but also uni-cellular organisms and even subcellular structures have convenient sizes. Flagella of eukaryotic cells are long dynamic cell protrusions. Because of their simple linear geometry, these cell appendages have been popular system for experimental investigation of the mechanisms of size control of organelles of eukaryotic cells. In the past most of the attention have been focussed on mono-flagellates and bi-flagellates. By extending our earlier model of bi-flagellates, here we develop a theoretical model for flagellar length control in {\it Giardia} which is an octo-flagellate. It has four pairs of flagella of four different lengths. Analyzing our model we predict the different sizes of the four pairs of flagella . This analysis not only provide insight into the physical origins of the different lengths but the predicted lengths are also consistent with the experimental data., Comment: Final version; Accepted for Publication in "Indian Journal of Physics", a pioneering journal founded by Sir C.V. Raman in 1926
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- 2021
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9. Galcanezumab in patients with episodic migraine: results from the open-label period of the phase 3 PERSIST study
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Zhou, Jiying, Zhong, Lianmei, Chowdhury, Debashish, Skorobogatykh, Kirill, Luo, Guogang, Yang, Xiaosu, Zhang, Mingjie, Sun, Lingli, Liu, Hui, Qian, Chenxi, and Yu, Shengyuan
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- 2023
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10. Flagellar length fluctuations: quantitative dependence on length control mechanism
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Patra, Swayamshree and Chowdhury, Debashish
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Physics - Biological Physics ,Nonlinear Sciences - Adaptation and Self-Organizing Systems ,Quantitative Biology - Subcellular Processes - Abstract
Organelles of optimum size are crucial for proper functioning of a living cell. The cell employs various mechanisms for actively sensing and controlling the size of its organelles. Recently Bauer et al have opened a new research frontier in the field of subcellular size control by shedding light on the noise and fluctuations of organelles of controlled size. Taking eukaryotic flagellum as a model organelle, which is quite popular for such studies because of its linear geometry and dynamic nature, Bauer et al have analysed the nature of fluctuations of its length. Here we summarize the key questions and the fundamental importance of the recent developments. Although our attention is focussed here mainly on the experimental and theoretical works on eukaryotic flagellum, the ideas are general and applicable to wide varieties of cell organelle., Comment: 3 pages, 1 figure
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- 2021
11. Decentralized decision making by an ant colony: drift-diffusion model of individual choice, quorum and collective decision
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Pradhan, Smriti, Patra, Swayamshree, and Chowdhury, Debashish
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Nonlinear Sciences - Adaptation and Self-Organizing Systems ,Physics - Biological Physics ,Physics - Physics and Society ,Quantitative Biology - Populations and Evolution - Abstract
Ants are social insects. When the existing nest of an ant colony becomes uninhabitable, the hunt for a new suitable location for migration of the colony begins. Normally, multiple sites may be available as the potential new nest site. Distinct sites may be chosen by different scout ants based on their own assessments. Since the individual assessment is error prone, many ants may choose inferior site(s). But, the collective decision that emerges from the sequential and decentralized decision making process is often far better. We develop a model for this multi-stage decision making process. A stochastic drift-diffusion model (DDM) captures the sequential information accumulation by individual scout ants for arriving at their respective individual choices. The subsequent tandem runs of the scouts, whereby they recruit their active nestmates, is modelled in terms of suitable adaptations of the totally asymmetric simple exclusion processes (TASEP). By a systematic analysis of the model we explore the conditions that determine the speed of the emergence of the collective decision and the quality of that decision. More specifically, we demonstrate that collective decision of the colony is much less error-prone that the individual decisions of the scout ants. We also compare our theoretical predictions with experimental data., Comment: 12 pages, including 4 figures and 1 table
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- 2021
12. Flagellar length control in monoflagellates by motorized transport: growth kinetics and correlations of length fluctuations
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Patra, Swayamshree and Chowdhury, Debashish
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Physics - Biological Physics ,Condensed Matter - Statistical Mechanics ,Quantitative Biology - Subcellular Processes - Abstract
How does a cell self-organize so that its appendages attain specific lengths that are convenient for their respective functions? What kind of 'rulers' does a cell use to measure the length of these appendages? How does a cell transport structure building materials between the cell body and distal tips of these appendages so as to regulate their dynamic lengths during various stages of its lifetime? Some of these questions are addressed here in the context of a specific cell appendage called flagellum (also called cilium). A "time of flight" (ToF) mechanism, adapted from the pioneering idea of Galileo, has been used successfully very recently to explain the length control of flagella by a biflagellate green algae. Using the same ToF mechanism, here we develop a stochastic model for the dynamics of flagella in two different types of monoflagellate unicellular organisms. A unique feature of these monoflagellates is that these become transiently multi-flagellated during a short span of their life time. The mean length of the flagella in our model reproduce the trend of their temporal variation observed in experiments. Moreover, for probing the intracellular molecular communication between the dynamic flagella of a given cell, we have computed the correlation in the fluctuations of their lengths during the multiflagellated stage of the cell cycle by Monte Carlo simulation., Comment: Accepted for Publication in "Physica A: Statistical Mechanics and its Applications"
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- 2020
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13. Comparison of Serum Holotranscobalamin with Serum Vitamin B12 in Population Prone to Megaloblastic Anemia and their Correlation with Nerve Conduction Study
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Verma, Abhishek, Aggarwal, Sunita, Garg, Sandeep, Kaushik, Smita, and Chowdhury, Debashish
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- 2023
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14. Level crossing statistics in a biologically motivated model of a long dynamic protrusion: passage times, random and extreme excursions
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Patra, Swayamshree and Chowdhury, Debashish
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Quantitative Biology - Subcellular Processes ,Condensed Matter - Statistical Mechanics ,Physics - Biological Physics - Abstract
Long cell protrusions, which are effectively one-dimensional, are highly dynamic subcellular structures. Length of many such protrusions keep fluctuating about the mean value even in the the steady state. We develop here a stochastic model motivated by length fluctuations of a type of appendage of an eukaryotic cell called flagellum (also called cilium). Exploiting the techniques developed for the calculation of level-crossing statistics of random excursions of stochastic process, we have derived analytical expressions of passage times for hitting various thresholds, sojourn times of random excursions beyond the threshold and the extreme lengths attained during the lifetime of these model flagella. We identify different parameter regimes of this model flagellum that mimic those of the wildtype and mutants of a well known flagellated cell. By analysing our model in these different parameter regimes, we demonstrate how mutation can alter the level-crossing statistics even when the steady state length remains unaffected by the same mutation. Comparison of the theoretically predicted level crossing statistics, in addition to mean and variance of the length, in the steady state with the corresponding experimental data can be used in near future as stringent tests for the validity of the models of flagellar length control. The experimental data required for this purpose, though never reported till now, can be collected, in principle, using a method developed very recently for flagellar length fluctuations., Comment: Thoroughly revised shorter version
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- 2020
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15. Flagellar length control in biflagellate eukaryotes: time-of-flight, shared pool, train traffic and cooperative phenomena
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Patra, Swayamshree, Jülicher, Frank, and Chowdhury, Debashish
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Physics - Biological Physics ,Condensed Matter - Statistical Mechanics ,Quantitative Biology - Subcellular Processes - Abstract
Flagella of eukaryotic cells are transient long cylindrical protrusions. The proteins needed to form and maintain flagella are synthesized in the cell body and transported to the distal tips. What `rulers' or `timers' a specific type of cells use to strike a balance between the outward and inward transport of materials so as to maintain a particular length of its flagella in the steady state is one of the open questions in cellular self-organization. Even more curious is how the two flagella of biflagellates, like Chlamydomonas Reinhardtii, communicate through their base to coordinate their lengths. In this paper we develop a stochastic model for flagellar length control based on a time-of-flight (ToF) mechanism. This ToF mechanism decides whether or not structural proteins are to be loaded onto an intraflagellar transport (IFT) train just before it begins its motorized journey from the base to the tip of the flagellum. Because of the ongoing turnover, the structural proteins released from the flagellar tip are transported back to the cell body also by IFT trains. We represent the traffic of IFT trains as a totally asymmetric simple exclusion process (TASEP). The ToF mechanism for each flagellum, together with the TASEP-based description of the IFT trains, combined with a scenario of sharing of a common pool of flagellar structural proteins in biflagellates, can account for all key features of experimentally known phenomena. These include ciliogenesis, resorption, deflagellation as well as regeneration after selective amputation of one of the two flagella. We also show that the experimental observations of Ishikawa and Marshall are consistent with the ToF mechanism of length control if the effects of the mutual exclusion of the IFT trains captured by the TASEP are taken into account. Moreover, we make new predictions on the flagellar length fluctuations and the role of the common pool., Comment: Revised presentation, 36 pages, including 17 figures
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- 2020
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16. Stochastic thermodynamics and modes of operation of a ribosome: a network theoretic perspective
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Dutta, Annwesha, Schütz, Gunter M, and Chowdhury, Debashish
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Condensed Matter - Statistical Mechanics ,Physics - Biological Physics ,Quantitative Biology - Subcellular Processes - Abstract
The ribosome is one of the largest and most complex macromolecular machines in living cells. It polymerizes a protein in a step-by-step manner as directed by the corresponding nucleotide sequence on the template messenger RNA (mRNA) and this process is referred to as `translation' of the genetic message encoded in the sequence of mRNA transcript. In each successful chemo-mechanical cycle during the (protein) elongation stage, the ribosome elongates the protein by a single subunit, called amino acid, and steps forward on the template mRNA by three nucleotides called a codon. Therefore, a ribosome is also regarded as a molecular motor for which the mRNA serves as the track, its step size is that of a codon and two molecules of GTP and one molecule of ATP hydrolyzed in that cycle serve as its fuel. What adds further complexity is the existence of competing pathways leading to distinct cycles, branched pathways in each cycle and futile consumption of fuel that leads neither to elongation of the nascent protein nor forward stepping of the ribosome on its track. We investigate a model formulated in terms of the network of discrete chemo-mechanical states of a ribosome during the elongation stage of translation. The model is analyzed using a combination of stochastic thermodynamic and kinetic analysis based on a graph-theoretic approach. We derive the exact solution of the corresponding master equations. We represent the steady state in terms of the cycles of the underlying network and discuss the energy transduction processes. We identify the various possible modes of operation of a ribosome in terms of its average velocity and mean rate of GTP hydrolysis. We also compute entropy production as functions of the rates of the interstate transitions and the thermodynamic cost for accuracy of the translation process., Comment: 62 pages; augmented model, new results, thoroughly revised text
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- 2019
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17. A biologically motivated three-species exclusion model: effects of leaky scanning and overlapping genes on initiation of protein synthesis
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Mishra, Bhavya and Chowdhury, Debashish
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Condensed Matter - Statistical Mechanics ,Nonlinear Sciences - Adaptation and Self-Organizing Systems ,Physics - Biological Physics ,Quantitative Biology - Subcellular Processes - Abstract
Totally asymmetric simple exclusion process (TASEP) was originally introduced as a model for the traffic-like collective movement of ribosomes on a messenger RNA (mRNA) that serves as the track for the motor-like forward stepping of individual ribosomes. In each step, a ribosome elongates a protein by a single unit using the track also as a template for protein synthesis. But, pre-fabricated, functionally competent, ribosomes are not available to begin synthesis of protein; a subunit directionally scans the mRNA in search of the pre-designated site where it is supposed to bind with the other subunit and begin the synthesis of the corresponding protein. However, because of `leaky' scanning, a fraction of the scanning subunits miss the target site and continue their search beyond the first target. Sometimes such scanners successfully identify the site that marks the site for initiation of the synthesis of a different protein. In this paper, we develop an exclusion model, with three interconvertible species of hard rods, to capture some of the key features of these biological phenomena and study the effects of the interference of the flow of the different species of rods on the same lattice. More specifically, we identify the meantime for the initiation of protein synthesis as appropriate mean {\it first-passage} time that we calculate analytically using the formalism of backward master equations. In spite of the approximations made, our analytical predictions are in reasonably good agreement with the numerical data that we obtain by performing Monte Carlo simulations. We also compare our results with a few experimental facts reported in the literature and propose new experiments for testing some of our new quantitative predictions., Comment: A new figure and discussions added
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- 2018
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18. A Biologically Motivated Asymmetric Exclusion Process: interplay of congestion in RNA polymerase traffic and slippage of nascent transcript
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Ghosh, Soumendu, Dutta, Annwesha, Patra, Shubhadeep, Sato, Jun, Nishinari, Katsuhiro, and Chowdhury, Debashish
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Condensed Matter - Statistical Mechanics ,Nonlinear Sciences - Adaptation and Self-Organizing Systems ,Physics - Biological Physics ,Quantitative Biology - Subcellular Processes - Abstract
We develope a theoretical framework, based on exclusion process, that is motivated by a biological phenomenon called transcript slippage (TS). In this model a discrete lattice represents a DNA strand while each of the particles that hop on it unidirectionally, from site to site, represents a RNA polymerase (RNAP). While walking like a molecular motor along a DNA track in a step-by-step manner, a RNAP simultaneously synthesizes a RNA chain; in each forward step it elongates the nascent RNA molecule by one unit, using the DNA track also as the template. At some special "slippery" position on the DNA, which we represent as a defect on the lattice, a RNAP can lose its grip on the nascent RNA and the latter's consequent slippage results in a final product that is either longer or shorter than the corresponding DNA template. We develope an exclusion model for RNAP traffic where the kinetics of the system at the defect site captures key features of TS events. We demonstrate the interplay of the crowding of RNAPs and TS. A RNAP has to wait at the defect site for longer period in a more congested RNAP traffic, thereby increasing the likelihood of its suffering a larger number of TS events. The qualitative trends of some of our results for a simple special case of our model are consistent with experimental observations. The general theoretical framework presented here will be useful for guiding future experimental queries and for analysis of the experimental data with more detailed versions of the same model., Comment: 14 pages, including 13 Figures
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- 2018
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19. First-passage processes on a filamentous track in a dense traffic: optimizing diffusive search for a target in crowding conditions
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Ghosh, Soumendu, Mishra, Bhavya, Kolomeisky, Anatoly B., and Chowdhury, Debashish
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Physics - Biological Physics ,Condensed Matter - Statistical Mechanics ,Nonlinear Sciences - Adaptation and Self-Organizing Systems ,Physics - Chemical Physics ,Quantitative Biology - Subcellular Processes - Abstract
Several important biological processes are initiated by the binding of a protein to a specific site on the DNA. The strategy adopted by a protein, called transcription factor (TF), for searching its specific binding site on the DNA has been investigated over several decades. In recent times the effects obstacles, like DNA-binding proteins, on the search by TF has begun to receive attention. RNA polymerase (RNAP) motors collectively move along a segment of the DNA during a genomic process called transcription. This RNAP traffic is bound to affect the diffusive scanning of the same segment of the DNA by a TF searching for its binding site. Motivated by this phenomenon, here we develop a kinetic model where a `particle', that represents a TF, searches for a specific site on a one-dimensional lattice. On the same lattice another species of particles, each representing a RNAP, hop from left to right exactly as in a totally asymmetric simple exclusion process (TASEP) which forbids simultaneous occupation of any site by more than one particle, irrespective of their identities. Although the TF is allowed to attach to or detach from any lattice site, the RNAPs can attach only to the first site at the left edge and detach from only the last site on the right edge of the lattice. We formulate the search as a {\it first-passage} process; the time taken to reach the target site {\it for the first time}, starting from a well defined initial state, is the search time. By approximate analytical calculations and Monte Carlo (MC) computer simulations, we calculate the mean search time. We show that RNAP traffic rectifies the diffusive motion of TF to that of a Brownian ratchet, and the mean time of successful search can be even shorter than that required in the absence of RNAP traffic. Moreover, we show that there is an optimal rate of detachment that corresponds to the shortest mean search time., Comment: 11 pages, including 6 Figures
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- 2018
20. Flagellar length control in multiflagellated eukaryotes: a case study with Giardia
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Patra, Swayamshree and Chowdhury, Debashish
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- 2022
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21. Clinical profile and quality of life in myasthenia gravis using MGQOL15 R(Hindi): An Indian perspective
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Majigoudra, Ganeshgouda, Duggal, Ashish, Chowdhury, Debashish, Koul, Arun, Todi, Vineet, and Roshan, Sujata
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Medical research ,Medicine, Experimental ,Myasthenia gravis -- Care and treatment ,Health - Abstract
Byline: Ganeshgouda. Majigoudra, Ashish. Duggal, Debashish. Chowdhury, Arun. Koul, Vineet. Todi, Sujata. Roshan Background: Myasthenia Gravis (MG) is a chronic fluctuating illness, due to the dysfunction of neuromuscular junction which [...]
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- 2023
22. Peer Review Report For: Research priorities for randomised controlled trials in chronic migraine preventive medication: A stakeholder consensus workshop [version 1; peer review: 1 approved with reservations]
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Chowdhury, Debashish, primary
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- 2024
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23. Interictal Dysfunctions of Attention, Vigilance, and Executive Functions in Migraine and Their Reversal by Preventive Treatment: A longitudinal Controlled Study
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Chowdhury, Debashish, primary, Datta, Debabrata, additional, Mundra, Ankit, additional, Duggal, Ashish, additional, and Krishnan, Anand, additional
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- 2024
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24. A pattern in the imaging data: mere artefact of spatio-temporal resolution
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Patra, Swayamshree, Dey, Swagata, Ray, Krishanu, and Chowdhury, Debashish
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Physics - Biological Physics ,Quantitative Biology - Quantitative Methods - Abstract
{\it ' Seeing is believing '} \cite{north06}- is the fundamental philosophy of optical imaging based on light microscopy \cite{ntziachristos10}. Since the pioneering works of Antonie van Leeuwenhoek and Robert Hooke in the 17th century, optical microscopy has served as one of the most important tools in biological sciences \cite{thorn16}. But interpreting visual observations with preconceived notions can potentially mislead one to erroneous conclusions.Here we report one such case where, at first sight, the interesting pattern extracted from the images of axonal transport may appear to reveal some hitherto unknown features of cargo transport driven by cytoskeletal motors \cite{ross16}. It may even be tempting to theorize about the possible molecular mechanisms that could give rise the observed pattern. But, as we conclusively demonstrate here, these patterns are mere artifacts of the spatial and temporal resolutions of imaging microscopes. These observed patterns, and their interpretations, are rather universal in the sense that in all those experiments where an observer (or machine), having limited spatial and temporal resolution, tracks the movement of classical objects moving on a one-dimensional track, such enticing patterns will invariably emerge. Our analysis here exposes pitfalls lurking in the way one interprets such patterns; unless critically analyzed, believing in whatever one is seeing, one could draw an illusory conclusion., Comment: Although technically sound, the interpretation is potentially misleading. We hope to report proper interpretation in future
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- 2018
25. Fidelity of bacterial translation initiation: a stochastic kinetic model
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Ghanti, Dipanwita, Caban, Kelvin, Frank, Joachim, Gonzalez, Jr., Ruben L., and Chowdhury, Debashish
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Physics - Biological Physics ,Physics - Chemical Physics ,Quantitative Biology - Subcellular Processes - Abstract
During the initiation stage of protein synthesis, a ribosomal initiation complex (IC) is assembled on a messenger RNA (mRNA) template. In bacteria, the speed and accuracy of this assembly process are regulated by the complementary activities of three essential initiation factors (IFs). Selection of an authentic N-formylmethionyl-transfer RNA (fMet-tRNA\textsuperscript{fMet}) and the canonical, triplet-nucleotide mRNA start codon are crucial events during assembly of a canonical, ribosomal 70S IC. Mis-initiation due to the aberrant selection of an elongator tRNA or a non-canonical start codon are rare events that result in the assembly of a pseudo 70S IC or a non-canonical 70S IC, respectively. Here, we have developed a theoretical model for the stochastic kinetics of canonical-, pseudo-, and non-canonical 70S IC assembly that includes all of the major steps of the IC assembly process that have been observed and characterized in ensemble kinetic-, single-molecule kinetic-, and structural studies of the fidelity of translation initiation. Specifically, we use the rates of the individual steps in the IC assembly process and the formalism of first-passage times to derive exact analytical expressions for the probability distributions for the assembly of canonical-, pseudo- and non-canonical 70S ICs. In order to illustrate the power of this analytical approach, we compare the theoretically predicted first-passage time distributions with the corresponding computer simulation data. We also compare the mean times required for completion of these assemblies with experimental estimates. In addition to generating new, testable hypotheses, our theoretical model can also be easily extended as new experimental 70S IC assembly data become available, thereby providing a versatile tool for interpreting these data and developing advanced models of the mechanism and regulation of translation initiation., Comment: Comments are welcome
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- 2018
26. A biologically inspired two-species exclusion model: effects of RNA polymerase motor traffic on simultaneous DNA replication
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Ghosh, Soumendu, Mishra, Bhavya, Patra, Shubhadeep, Schadschneider, Andreas, and Chowdhury, Debashish
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Quantitative Biology - Subcellular Processes ,Condensed Matter - Statistical Mechanics ,Physics - Biological Physics - Abstract
We introduce a two-species exclusion model to describe the key features of the conflict between the RNA polymerase (RNAP) motor traffic, engaged in the transcription of a segment of DNA, concomitant with the progress of two DNA replication forks on the same DNA segment. One of the species of particles ($P$) represents RNAP motors while the other ($R$) represents replication forks. Motivated by the biological phenomena that this model is intended to capture, a maximum of only two $R$ particles are allowed to enter the lattice from two opposite ends whereas the unrestricted number of $P$ particles constitute a totally asymmetric simple exclusion process (TASEP) in a segment in the middle of the lattice. Consequently, the lattice consists of three segments; the encounters of the $P$ particles with the $R$ particles are confined within the middle segment (segment $2$) whereas only the $R$ particles can occupy the sites in the segments $1$ and $3$. The model captures three distinct pathways for resolving the co-directional as well as head-collision between the $P$ and $R$ particles. Using Monte Carlo simulations and heuristic analytical arguments that combine exact results for the TASEP with mean-field approximations, we predict the possible outcomes of the conflict between the traffic of RNAP motors ($P$ particles engaged in transcription) and the replication forks ($R$ particles). The outcomes, of course, depend on the dynamical phase of the TASEP of $P$ particles. In principle, the model can be adapted to the experimental conditions to account for the data quantitatively., Comment: 10 pages, including 7 figures
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- 2017
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27. A Multispecies Exclusion Process with Fusion and Fission of Rods: a model inspired by Intraflagellar Transport
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Patra, Swayamshree and Chowdhury, Debashish
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Condensed Matter - Statistical Mechanics - Abstract
We introduce a multispecies exclusion model where length-conserving probabilistic fusion and fission of the hard rods are allowed. Although all rods enter the system with the same initial length ${\ell}=1$, their length can keep changing, because of fusion and fission, as they move in a step-by-step manner towards the exit. Two neighboring hard rods of lengths ${\ell}_{1}$ and ${\ell}_{2}$ can fuse into a single rod of longer length ${\ell}={\ell}_{1}+{\ell}_{2}$ provided ${\ell} \leq N$. Similarly, length-conserving fission of a rod of length ${\ell}' \leq N$ results in two shorter daughter rods. Based on the extremum current hypothesis, we plot the phase diagram of the model under open boundary conditions utilizing the results derived for the same model under periodic boundary condition using mean-field approximation. The density profile and the flux profile of rods are in excellent agreement with computer simulations. Although the fusion and fission of the rods are motivated by similar phenomena observed in Intraflagellar Transport (IFT) in eukaryotic flagella, this exclusion model is too simple to account for the quantitative experimental data for any specific organism. Nevertheless, the concepts of `flux profile' and `transition zone' that emerge from the interplay of fusion and fission in this model are likely to have important implications for IFT and for other similar transport phenomena in long cell protrusions., Comment: 20 pages, including 10 figures; thoroughly revised incorporating new results and discussions
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- 2017
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28. Michaelis-Menten at 100 and allosterism at 50: driving molecular motors in a hailstorm with noisy ATPase engines and allosteric transmission
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Chowdhury, Debashish
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Physics - Biological Physics ,Physics - Chemical Physics ,Quantitative Biology - Subcellular Processes - Abstract
Cytoskeletal motor proteins move on filamentous tracks by converting input chemical energy that they derive by catalyzing the hydrolysis of ATP. The ATPase site is the analog of an engine and hydrolysis of ATP is the analog of burning of chemical fuel. Moreover, the functional role of a segment of the motor is analogous to that of the transmission system of an automobile that consists of shaft, gear, clutch, etc. The operation of the engine is intrinsically "noisy" and the motor faces a molecular "hailstorm" in the aqueous medium. In this commemorative article, we celebrate the centenary of Michaelis and Menten's landmark paper of 1913 and the golden jubilee of Monod et al.'s classic paper of 1963 by highlighting their relevance in explaining the operational mechanisms of the engine and the transmission system, respectively, of cytoskeletal motors., Comment: This is an author-created, un-copyedited version of an article published in FEBS Journal (Federation of European Biochem. Soc.)
- Published
- 2017
- Full Text
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29. Quantitative Connection Between Ensemble Thermodynamics and Single-Molecule Kinetics: A Case Study Using Cryogenic Electron Microscopy and Single-Molecule Fluorescence Resonance Energy Transfer Investigations of the Ribosome
- Author
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Kinz-Thompson, Colin D., Sharma, Ajeet K., Frank, Joachim, Gonzalez, Jr., Ruben L., and Chowdhury, Debashish
- Subjects
Physics - Biological Physics ,Condensed Matter - Statistical Mechanics ,Physics - Chemical Physics ,Quantitative Biology - Subcellular Processes - Abstract
At equilibrium, thermodynamic and kinetic information can be extracted from biomolecular energy landscapes by many techniques. However, while static, ensemble techniques yield thermodynamic data, often only dynamic, single-molecule techniques can yield the kinetic data that describes transition-state energy barriers. Here we present a generalized framework based upon dwell-time distributions that can be used to connect such static, ensemble techniques with dynamic, single-molecule techniques, and thus characterize energy landscapes to greater resolutions. We demonstrate the utility of this framework by applying it to cryogenic electron microscopy (cryo-EM) and single-molecule fluorescence resonance energy transfer (smFRET) studies of the bacterial ribosomal pre-translocation complex. Among other benefits, application of this framework to these data explains why two transient, intermediate conformations of the pre-translocation complex, which are observed in a cryo-EM study, may not be observed in several smFRET studies., Comment: 43 pages, including 6 figures
- Published
- 2017
- Full Text
- View/download PDF
30. First Passage Time in Computation by Tape-Copying Turing Machines: Slippage of Nascent Tape
- Author
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Ghosh, Soumendu, Patra, Shubhadeep, and Chowdhury, Debashish
- Subjects
Physics - Biological Physics ,Condensed Matter - Statistical Mechanics ,Physics - Chemical Physics ,Quantitative Biology - Subcellular Processes - Abstract
Transcription of the genetic message encoded chemically in the sequence of the DNA template is carried out by a molecular machine called RNA polymerase (RNAP). Backward or forward slippage of the nascent RNA with respect to the DNA template strand give rise to a transcript that is, respectively, longer or shorter than the corresponding template. We model a RNAP as a "Tape-copying Turing machine" (TCTM) where the DNA template is the input tape while the nascent RNA strand is the output tape. Although the TCTM always steps forward the process is assumed to be stochastic that has a probability of occurrence per unit time. The time taken by a TCTM for each single successful forward stepping on the input tape, during which the output tape suffers lengthening or shortening by $n$ units because of backward or forward slippage, is a random variable; we report some of the statistical characteristics of this time by using the formalism for calculation of the distributions of {\it first-passage time}. The results are likely to find applications in the analysis of experimental data on "programmed" transcriptional error caused by transcriptional slippage which is a mode of "recoding" of genetic information., Comment: 10 pages, including 5 Figures
- Published
- 2017
31. Interference of two co-directional exclusion processes in the presence of a static bottleneck: a biologically motivated model
- Author
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Mishra, Bhavya and Chowdhury, Debashish
- Subjects
Physics - Biological Physics ,Condensed Matter - Statistical Mechanics ,Quantitative Biology - Subcellular Processes - Abstract
We develope a two-species exclusion process with a distinct pair of entry and exit sites for each species of rigid rods. The relatively slower forward stepping of the rods in an extended bottleneck region, located in between the two entry sites, controls the extent of interference of the co-directional flow of the two species of rods. The relative positions of the sites of entry of the two species of rods with respect to the location of the bottleneck are motivated by a biological phenomenon. However, the primary focus of the study here is to explore the effects of the interference of the flow of the two species of rods on their spatio-temporal organization and the regulations of this interference by the extended bottleneck. By a combination of mean-field theory and computer simulation we calculate the flux of both species of rods and their density profiles as well as the composite phase diagrams of the system. If the bottleneck is sufficiently stringent some of the phases become practically unrealizable although not ruled out on the basis of any fundamental physical principle. Moreover the extent of suppression of flow of the downstream entrants by the flow of the upstream entrants can also be regulated by the strength of the bottleneck. We speculate on the possible implications of the results in the context of the biological phenomenon that motivated the formulation of the theoretical model., Comment: This is an author-created, un-copyedited final preprint version of an article published in Physical Review E (APS)
- Published
- 2017
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32. Strength and stability of active ligand-receptor bonds: a microtubule attached to a wall by molecular motor tethers
- Author
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Ghanti, Dipanwita, Friddle, Raymond W., and Chowdhury, Debashish
- Subjects
Quantitative Biology - Subcellular Processes ,Physics - Biological Physics ,Physics - Chemical Physics - Abstract
We develop a stochastic kinetic model of a pre-formed attachment of a mictrotuble (MT) with a cell cortex, in which the MT is tethered to the cell by a group of active motor proteins. Such an attachment is a particularly unique case of ligand-receptor bonds: The MT ligand changes its length (and thus binding sites) with time by polymerization-depolymerization kinetics, while multiple motor receptors tend to walk actively along the MT length. These processes, combined with force-mediated unbinding of the motors, result in an elaborate behavior of the MT connection to the cell cortex. We present results for the strength and lifetime of the system through the well-established force-clamp and force-ramp protocols when external tension is applied to the MT. The simulation results reveal that the MT-cell attachment behaves as a catch-bond or slip-bond depending on system parameters. We provide analytical approximations of the lifetime and discuss implications of our results on in-vitro experiments., Comment: Thoroughly revised model, data, figures, text, bibliography and authorship
- Published
- 2016
- Full Text
- View/download PDF
33. Clinical profile and outcome of non-COVID strokes during pandemic and the pre pandemic period: COVID-Stroke Study Group (CSSG) India
- Author
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Bhatia, Rohit, Sylaja, P.N., Srivastava, M.V. Padma, Komakula, Snigdha, Iype, Thomas, Parthasarathy, Rajsrinivas, Khurana, Dheeraj, Pardasani, Vibhor, Pamidimukkala, Vijaya, Kumaravelu, S., Pandian, Jeyaraj, Kushwaha, Suman, Chowdhury, Debashish, Gupta, Salil, Rajendran, Srijithesh P., Reddy, Rajshekar, Roy, Jayanta, Sharma, Arvind, Nambiar, Vivek, Rai, Nirendra Kumar, Upadhyay, Ashish Datt, Parkipandla, Sathish, Singh, Mamta Bhushan, Vibha, Deepti, Vishnu, Venugopalan Y., Rajan, Roopa, Gupta, Anu, Pandit, Awadh Kishore, Agarwal, Ayush, Gaikwad, Shailesh B., Garg, Ajay, Joseph, Leve, Sreedharan, Sapna Erat, Reddy, Sritheja, Sreela, Krishna, Ramachandran, Dileep, George, Githin Benoy, Panicker, Praveen, Suresh, M.K., Gupta, Vipul, Ray, Sucharita, Suri, Vikas, Ahuja, Chirag, Kajal, Kamal, Lal, Vivek, Singh, Rakesh K., Oza, Harsh, Halani, Hiral, Sanivarapu, Srinivasareddy, Sahonta, Rajeshwar, Duggal, Ashish, Dixit, Prashant, Kulkarni, Girish Baburao, Taallapalli, A.V.R., Parmar, Mamta, Chalasani, Vamsi, Kashyap, Manshi, Misra, Biswamohan, Pachipala, Sudheer, Yogeesh, P.M., Salunkhe, Manish, and Gupta, Pranjal
- Published
- 2021
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34. Anti-N-methyl D-aspartate receptor encephalitis in India: A literature review
- Author
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Chowdhury, Debashish, Panda, Ashwin, Gupta, Ashutosh, Chowdhury, Samiran, Duggal, Ashish, and Koul, Arun
- Subjects
Encephalitis -- Statistics -- Care and treatment -- Diagnosis ,Autoimmune diseases -- Statistics -- Care and treatment -- Diagnosis ,Health - Abstract
Byline: Debashish. Chowdhury, Ashwin. Panda, Ashutosh. Gupta, Samiran. Chowdhury, Ashish. Duggal, Arun. Koul Anti N-methyl D-aspartate receptor encephalitis (NMDAR-E) though rare, is currently considered as the commonest antibody mediated encephalitis [...]
- Published
- 2023
35. Molecular force spectroscopy of kinetochore-microtubule attachment {\it in silico}: Mechanical signatures of an unusual catch bond and collective effects
- Author
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Ghanti, Dipanwita, Patra, Shubhadeep, and Chowdhury, Debashish
- Subjects
Physics - Biological Physics ,Quantitative Biology - Subcellular Processes - Abstract
Measurement of the life time of attachments formed by a single microtubule (MT) with a single kinetochore (kt) {\it in-vitro} under force-clamp conditions had earlier revealed a catch-bond-like behavior. In the past the physical origin of this apparently counter-intuitive phenomenon was traced to the nature of the force-dependence of the (de-)polymerization kinetics of the MTs. Here first the same model MT-kt attachment is subjected to external tension that increases linearly with time until rupture occurs. In our {\it force-ramp} experiments {\it in-silico}, the model displays the well known `mechanical signatures' of a catch-bond probed by molecular force spectroscopy. Exploiting this new evidence, we have further strengthened the analogy between MT-kt attachments and common ligand-receptor bonds in spite of the crucial differences in their underlying physical mechanisms. We then extend the formalism to model the stochastic kinetics of an attachment formed by a bundle of multiple parallel microtubules with a single kt considering the effect of rebinding under force-clamp and force-ramp conditions. From numerical studies of the model we predict the trends of variation of the mean life time and mean rupture force with the increasing number of MTs in the bundle. Both the mean life time and the mean rupture force display nontrivial nonlinear dependence on the maximum number of MTs that can attach simultaneously to the same kt., Comment: Thoroughly revised final version; published in Physical Review E
- Published
- 2016
- Full Text
- View/download PDF
36. Slip of grip of a molecular motor on a crowded track: Modeling shift of reading frame of ribosome on RNA template
- Author
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Mishra, Bhavya, Schütz, Gunter M., and Chowdhury, Debashish
- Subjects
Physics - Biological Physics ,Quantitative Biology - Subcellular Processes - Abstract
We develop a stochastic model for the programmed frameshift of ribosomes synthesizing a protein while moving along a mRNA template. Normally the reading frame of a ribosome decodes successive triplets of nucleotides on the mRNA in a step-by-step manner. We focus on the programmed shift of the ribosomal reading frame, forward or backward, by only one nucleotide which results in a fusion protein; it occurs when a ribosome temporarily loses its grip to its mRNA track. Special "slippery" sequences of nucleotides and also downstream secondary structures of the mRNA strand are believed to play key roles in programmed frameshift. Here we explore the role of an hitherto neglected parameter in regulating -1 programmed frameshift. Specifically, we demonstrate that the frameshift frequency can be strongly regulated also by the density of the ribosomes, all of which are engaged in simultaneous translation of the same mRNA, at and around the slippery sequence. Monte Carlo simulations support the analytical predictions obtained from a mean-field analysis of the stochastic dynamics., Comment: This is an author-created, un-copyedited final version of an article published in EPL
- Published
- 2016
- Full Text
- View/download PDF
37. A generalized Michaelis-Menten equation in protein synthesis: effects of mis-charged cognate tRNA and mis-reading of codon
- Author
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Dutta, Annwesha and Chowdhury, Debashish
- Subjects
Physics - Biological Physics ,Quantitative Biology - Quantitative Methods ,Quantitative Biology - Subcellular Processes - Abstract
The sequence of amino acid monomers in the primary structure of a protein is decided by the corresponding sequence of codons (triplets of nucleic acid monomers) on the template messenger RNA (mRNA). The polymerization of a protein, by incorporation of the successive amino acid monomers, is carried out by a molecular machine called ribosome. We develop a stochastic kinetic model that captures the possibilities of mis-reading of mRNA codon and prior mis-charging of a tRNA. By a combination of analytical and numerical methods we obtain the distribution of the times taken for incorporation of the successive amino acids in the growing protein in this mathematical model. The corresponding exact analytical expression for the average rate of elongation of a nascent protein is a `biologically motivated' generalization of the {\it Michaelis-Menten formula} for the average rate of enzymatic reactions. This generalized Michaelis-Menten-like formula (and the exact analytical expressions for a few other quantities) that we report here display the interplay of four different branched pathways corresponding to selection of four different types of tRNA., Comment: This is an author-created, un-copyedited version of an article published in BULLETIN OF MATHEMATICAL BIOLOGY (Official Journal of The Society for Mathematical Biology)
- Published
- 2015
- Full Text
- View/download PDF
38. A Multispecies Exclusion Model Inspired By Transcriptional Interference
- Author
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Ghosh, Soumendu, Bameta, Tripti, Ghanti, Dipanwita, and Chowdhury, Debashish
- Subjects
Physics - Biological Physics ,Condensed Matter - Statistical Mechanics ,Nonlinear Sciences - Adaptation and Self-Organizing Systems ,Quantitative Biology - Subcellular Processes - Abstract
We introduce exclusion models of two distinguishable species of hard rods with their distinct sites of entry and exit under open boundary conditions. In the first model both species of rods move in the same direction whereas in the other two models they move in the opposite direction. These models are motivated by the biological phenomenon known as Transcriptional Interference. Therefore, the rules for the kinetics of the models, particularly the rules for the outcome of the encounter of the rods, are also formulated to mimic those observed in Transcriptional Interference. By a combination of mean-field theory and computer simulation of these models we demonstrate how the flux of one species of rods is completely switched off by the other. Exploring the parameter space of the model we also establish the conditions under which switch-like regulation of two fluxes is possible; from the extensive analysis we discover more than one possible mechanism of this phenomenon., Comment: This is an author-created, un-copyedited version of an article published in the Journal of Statistical Mechanics: Theory and Experiment. IOP Publishing Ltd is not responsible for any errors or omissions in this version of the manuscript or any version derived from it
- Published
- 2015
- Full Text
- View/download PDF
39. Flux-density relation for traffic of army ants in a 3-lane bi-directional trail
- Author
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Pradhan, Smriti, Patra, Swayamshree, Dai, Yasar Efe, Schadschneider, Andreas, and Chowdhury, Debashish
- Published
- 2021
- Full Text
- View/download PDF
40. Flagellar length control in monoflagellates by motorized transport: Growth kinetics and correlations of length fluctuations
- Author
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Patra, Swayamshree and Chowdhury, Debashish
- Published
- 2021
- Full Text
- View/download PDF
41. Mixed molecular motor traffic on nucleic acid tracks: models of transcriptional interference and regulation of gene expression
- Author
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Bameta, Tripti, Chowdhury, Debashish, Ghanti, Dipanwita, and Ghosh, Soumendu
- Subjects
Physics - Biological Physics ,Condensed Matter - Statistical Mechanics ,Nonlinear Sciences - Adaptation and Self-Organizing Systems ,Quantitative Biology - Subcellular Processes - Abstract
RNA polymerase (RNAP) is molecular machine that polymerizes a RNA molecule, a linear heteropolymer, using a single stranded DNA (ssDNA) as the corresponding template; the sequence of monomers of the RNA is dictated by that of monomers on the ssDNA template. While polymerizing a RNA, the RNAP walks step-by-step on the ssDNA template in a specific direction. Thus, a RNAP can be regarded also as a molecular motor and the sites of start and stop of its walk on the DNA mark the two ends of the genetic message that it transcribes into RNA. Interference of transcription of two overlapping genes is believed to regulate the levels of their expression, i.e., the overall rate of the corresponding RNA synthesis, through suppressive effect of one on the other. Here we model this process as a mixed traffic of two groups of RNAP motors that are characterized by two distinct pairs of start and stop sites. Each group polymerizes identical copies of a RNA while the RNAs polymerized by the two groups are different. These models, which may also be viewed as two interfering totally asymmetric simple exclusion processes, account for all modes of transcriptional interference in spite of their extreme simplicity. A combination of mean-field theory and computer simulation of these models demonstrate the physical origin of the switch-like regulation of the two interfering genes in both co-directional and contra-directional traffic of the two groups of RNAP motors., Comment: 6+ pages, including 4 figures
- Published
- 2015
42. Single-enzyme kinetics with branched pathways: exact theory and series expansion
- Author
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Garai, Ashok and Chowdhury, Debashish
- Subjects
Physics - Chemical Physics ,Condensed Matter - Statistical Mechanics ,Physics - Biological Physics ,Quantitative Biology - Subcellular Processes - Abstract
The progress of the successive rounds of catalytic conversion of substrates into product(s) by a single enzyme is characterized by the distribution of turnover times. Establishing the most general form of dependence of this distribution on the substrate concentration [S] is one of the fundamental challenges in single molecule enzymology. The distribution of the times of dwell of a molecular motor at the successive positions on its track is an analogous quantity. We derive approximate series expansions for the [ATP]-dependence of the first two moments of the dwell time distributions of motors that catalyze hydrolysis of ATP to draw input energy. Comparison between our results for motors with branched pathways and the corresponding expressions reported earlier for linear enzymatic pathways provides deep insight into the effects of the branches. Such insight is likely to help in discovering the most general form of [S]-dependence of these fundamental distributions., Comment: 5 pages, including 4 figures
- Published
- 2014
43. Collective cargo hauling by a bundle of parallel microtubules: bi-directional motion caused by load-dependent polymerization and depolymerization
- Author
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Ghanti, Dipanwita and Chowdhury, Debashish
- Subjects
Quantitative Biology - Subcellular Processes ,Condensed Matter - Statistical Mechanics ,Nonlinear Sciences - Adaptation and Self-Organizing Systems ,Physics - Biological Physics - Abstract
A microtubule (MT) is a hollow tube of approximately 25 nm diameter. The two ends of the tube are dissimilar and are designated as `plus' and `minus' ends. Motivated by the collective push and pull exerted by a bundle of MTs during chromosome segregation in a living cell, we have developed here a much simplified theoretical model of a bundle of parallel dynamic MTs. The plus-end of all the MTs in the bundle are permanently attached to a movable `wall' by a device whose detailed structure is not treated explicitly in our model. The only requirement is that the device allows polymerization and depolymerization of each MT at the plus-end. In spite of the absence of external force and direct lateral interactions between the MTs, the group of polymerizing MTs attached to the wall create a load force against the group of depolymerizing MTs and vice-versa; the load against a group is shared equally by the members of that group. Such indirect interactions among the MTs gives rise to the rich variety of possible states of collective dynamics that we have identified by computer simulations of the model in different parameter regimes. The bi-directional motion of the cargo, caused by the load-dependence of the polymerization kinetics, is a "proof-of-principle" that the bi-directional motion of chromosomes before cell division does not necessarily need active participation of motor proteins., Comment: This is an author-created, un-copyedited version of an article published in the Journal of Statistical Mechanics: Theory and Experiment. IOP Publishing Ltd is not responsible for any errors or omissions in this version of the manuscript or any version derived from it
- Published
- 2014
- Full Text
- View/download PDF
44. TASEP on parallel tracks: effects of mobile bottlenecks in fixed segments
- Author
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Sinha, Sumit and Chowdhury, Debashish
- Subjects
Condensed Matter - Statistical Mechanics ,Nonlinear Sciences - Adaptation and Self-Organizing Systems - Abstract
We study the flux of totally asymmetric simple exclusion processes (TASEPs) on a twin co-axial square tracks. In this biologically motivated model the particles in each track act as mobile bottlenecks against the movement of the particles in the other although the particle are not allowed to move out of their respective tracks. So far as the outer track is concerned, the particles on the inner track act as bottlenecks only over a set of fixed segments of the outer track, in contrast to site-associated and particle-associated quenched randomness in the earlier models of disordered TASEP. In a special limiting situation the movement of particles in the outer track mimic a TASEP with a "point-like" immobile (i.e., quenched) defect where phase segregation of the particles is known to take place. The length of the inner track as well as the strength and number density of the mobile bottlenecks moving on it are the control parameters that determine the nature of spatio-temporal organization of particles on the outer track. Variation of these control parameters allow variation of the width of the phase-coexistence region on the flux-density plane of the outer track. Some of these phenomena are likely to survive even in the future extensions intended for studying traffic-like collective phenomena of polymerase motors on double-stranded DNA., Comment: This is an author-created, un-copyedited final version of the article published in PHYSICA A (copyright Elsevier). Elsevier is not responsible for any errors or omissions in this version of the manuscript or any version derived from it
- Published
- 2014
- Full Text
- View/download PDF
45. Abhijit Mookerjee (1946–2019)
- Author
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Chowdhury, Debashish and Roy, Sindhunil Barman
- Published
- 2019
46. Centenary of 'Researches on irritability of plants' by Jagadis Chandra Bose
- Author
-
Chowdhury, Debashish
- Subjects
Physics - History and Philosophy of Physics ,Quantitative Biology - Other Quantitative Biology - Abstract
This note celebrates the centenary of Jagadis Chandra Bose's classic monograph entitled "Researches on irritability of plants"., Comment: This is an author-created, un-copyedited final version of the article published in CURRENT SCIENCE (published by Current Science Association, in collaboration with Indian Academy of Sciences)
- Published
- 2013
47. Distribution of lifetimes of kinetochore-microtubule attachments: interplay of energy landscape, molecular motors and microtubule (de-)polymerization
- Author
-
Sharma, Ajeet K., Shtylla, Blerta, and Chowdhury, Debashish
- Subjects
Physics - Biological Physics ,Condensed Matter - Statistical Mechanics ,Quantitative Biology - Subcellular Processes - Abstract
Before a cell divides into two daughter cells, chromosomes are replicated resulting in two sister chromosomes embracing each other. Each sister chromosome is bound to a separate proteinous structure, called kinetochore (kt), that captures the tip of a filamentous protein, called microtubule (MT). Two oppositely oriented MTs pull the two kts attached to two sister chromosomes thereby pulling the two sisters away from each other. Here we theoretically study an even simpler system, namely an isolated kt coupled to a single MT; this system mimics an {\it in-vitro} experiment where a single kt-MT attachment is reconstituted using purified extracts from budding yeast. Our models not only account for the experimentally observed "catch-bond-like" behavior of the kt-MT coupling, but also make new predictions on the probability distribution of the lifetimes of the attachments. In principle, our new predictions can be tested by analyzing the data collected in the {\it in-vitro} experiments provided the experiment is repeated sufficiently large number of times. Our theory provides a deep insight into the effects of (a) size, (b) energetics, and (c) stochastic kinetics of the kt-MT coupling on the distribution of the lifetimes of these attachments., Comment: This is an author-created, un-copyedited version of an article accepted for publication in "Physical Biology" (IOP). IOP Publishing Ltd is not responsible for any errors or omissions in this version of the manuscript or any version derived from it
- Published
- 2013
- Full Text
- View/download PDF
48. A theoretical model for attachment lifetimes of kinetochore-microtubules: Mechano-kinetic 'catch-bond' mechanism for error-correction
- Author
-
Shtylla, Blerta and Chowdhury, Debashish
- Subjects
Physics - Biological Physics ,Condensed Matter - Statistical Mechanics ,Quantitative Biology - Subcellular Processes - Abstract
Before cell division, two identical copies of chromosomes are pulled apart by microtubule (MT) filaments that approach the chromosomes from the opposite poles a mitotic spindle. Connection between the MTs and the chromosomes are mediated by a molecular complex called kinetochore. An externally applied tension can lead to detachment of the MTs from the kinetochore; the mean lifetime of such an attachment is essentially a mean first-passage time. In their in-vitro pioneering single-kinetochore experiments, Akiyoshi et al. (Nature 468, 576 (2010)), observed that the mean lifetimes of reconstituted MT-kinetochore attachments vary non-monotonically with increasing tension. The counter-intuitive stabilization of the attachments by small load forces was interpreted in terms of a catch-bond-like mechanism based on a phenomenological 2-state kinetic model. Here we develop the first detailed microscopic model for studying the dependence of the lifetime of the MT-kinetochore attachment on (a) the structure, (b) energetics, and (c) kinetics of the coupling. The catch-bond-like mechanism emerges naturally from this model. Moreover, in-silico experiments on this model reveal further interesting phenomena, arising from the subtle effects of competing sub-processes, which are likely to motivate new experiments in this emerging area of single-particle biophysics.
- Published
- 2013
49. First-passage problems in DNA replication: effects of template tension on stepping and exonuclease activities of a DNA polymerase motor
- Author
-
Sharma, Ajeet K. and Chowdhury, Debashish
- Subjects
Quantitative Biology - Subcellular Processes ,Condensed Matter - Statistical Mechanics ,Physics - Biological Physics - Abstract
A DNA polymerase (DNAP) replicates a template DNA strand. It also exploits the template as the track for its own motor-like mechanical movement. In the polymerase mode it elongates the nascent DNA by one nucleotide in each step. But, whenever it commits an error by misincorporating an incorrect nucleotide, it can switch to an exonuclease mode. In the latter mode it excises the wrong nucleotide before switching back to its polymerase mode. We develop a stochastic kinetic model of DNA replication that mimics an {\it in-vitro} experiment where a single-stranded DNA, subjected to a mechanical tension $F$, is converted to a double-stranded DNA by a single DNAP. The $F$-dependence of the average rate of replication, which depends on the rates of both polymerase and exonuclease activities of the DNAP, is in good qualitative agreement with the corresponding experimental results. We introduce 9 novel distinct {\it conditional dwell times} of a DNAP. Using the methods of first-passage times, we also derive the exact analytical expressions for the probability distributions of these conditional dwell times. The predicted $F$-dependence of these distributions are, in principle, accessible to single-molecule experiments., Comment: 24 pages, including 5 figures; final version accepted for publication in the Special Issue on "physics of protein motility and motor proteins" in Journal of Physics: Condensed Matter
- Published
- 2013
- Full Text
- View/download PDF
50. Template-directed biopolymerization: tape-copying Turing machines
- Author
-
Sharma, Ajeet K. and Chowdhury, Debashish
- Subjects
Physics - Biological Physics ,Condensed Matter - Statistical Mechanics - Abstract
DNA, RNA and proteins are among the most important macromolecules in a living cell. These molecules are polymerized by molecular machines. These natural nano-machines polymerize such macromolecules, adding one monomer at a time, using another linear polymer as the corresponding template. The machine utilizes input chemical energy to move along the template which also serves as a track for the movements of the machine. In the Alan Turing year 2012, it is worth pointing out that these machines are "tape-copying Turing machines". We review the operational mechanisms of the polymerizer machines and their collective behavior from the perspective of statistical physics, emphasizing their common features in spite of the crucial differences in their biological functions. We also draw attention of the physics community to another class of modular machines that carry out a different type of template-directed polymerization. We hope this review will inspire new kinetic models for these modular machines., Comment: Author-edited final version of a review article published in Biophysical Reviews and Letters [copyright World Scientific Publishing Company]; publisher-edited electronic version available at http://www.worldscientific.com/doi/abs/10.1142/S1793048012300083
- Published
- 2012
- Full Text
- View/download PDF
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