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Physical Biology

Barbara Bravi, Peter Sollich
We apply a Gaussian variational approximation to model reduction in large biochemical networks of unary and binary reactions. We focus on a small subset of variables (subnetwork) of interest, e.g. because they are accessible experimentally, embedded in a larger network (bulk). The key goal is to write dynamical equations reduced to the subnetwork but still retaining the effects of the bulk. As a result, the subnetwork-reduced dynamics contains a memory term and an extrinsic noise term with non-trivial temporal correlations...
May 16, 2017: Physical Biology
Jennifer Israel Cohen, Jeroen Heijst, Jacob Glanville, Yoram Louzoun
T and B cell receptor (TCR and BCR) complementarity determining region 3 (CDR3) genetic diversity is produced through multiple diversification and selection stages. Potential holes in the CDR3 repertoire were argued to be linked to immunodeficiencies and diseases. In contrast with BCRs, TCRs have practically no Dβ germline genetic diversity, and the question whether they can produce a diverse CDR3 repertoire emerges. In order to address the genetic diversity of the adaptive immune system, appropriate quantitative measures for diversity and large scale sequencing are required...
May 16, 2017: Physical Biology
Xingbo Yang, Kelson Kaj, David Schwab, Eva-Maria Schoetz Collins
Uncovering the mechanisms that control size, growth, and division rates of systems reproducing through binary division means understanding basic principles of their life cycle. Recent work has focused on how division rates are regulated in bacteria and yeast, but this question has not yet been addressed in more complex, multicellular organisms. We have acquired a unique large-scale data set on the growth and asexual reproduction of two freshwater planarian species, Dugesia japonica and Dugesia tigrina, which reproduce by transverse fission and succeeding regeneration of head and tail pieces into new planarians...
May 3, 2017: Physical Biology
Dongya Jia, Mohit Kumar Jolly, William Harrison, Marcelo Boareto, Eshel Ben-Jacob, Herbert Levine
Many cell-fate decisions during embryonic development are governed by a motif comprised of two transcription factors (TFs) A and B that mutually inhibit each other and may self-activate. This motif, called as a self-activating toggle switch (SATS), can typically have three stable states (phenotypes) - two corresponding to differentiated cell fates, each of which has a much higher level of one TF than the other - (A, B) = (1,0) or (0,1) - and the third state corresponding to an 'undecided' stem-like state with similar levels of both A and B - (A, B) = (1/2,1/2)...
April 26, 2017: Physical Biology
Sean D Lawley, James Keener
The behavior of many biochemical processes depends crucially on molecules rapidly rebinding after dissociating. In the case of multisite protein modification, the importance of rebinding has been demonstrated both experimentally and through several recent computational studies involving stochastic spatial simulations. As rebinding stems from spatio-temporal correlations, theorists have resorted to models that explicitly include space to properly account for the effects of rebinding. However, for reactions in three space dimensions it was recently shown that well-mixed ordinary differential equation (ODE) models can incorporate rebinding by adding connections to the reaction network...
April 26, 2017: Physical Biology
Isabell Weber, Seok-Hyun Yun, Guillano Scarcelli, Kristian Franze
Cells in the central nervous system (CNS) respond to the stiffness of their environment. CNS tissue is mechanically highly heterogeneous, thus providing motile cells with region-specific mechanical signals. While CNS mechanics has been measured with a variety of techniques, reported values of tissue stiffness vary greatly, and the morphological structures underlying spatial changes in tissue stiffness remain poorly understood. We here exploited two complementary techniques, contact-based atomic force microscopy and contact-free Brillouin microscopy, to determine the mechanical properties of ruminant retinae, which are built up by different tissue layers...
April 13, 2017: Physical Biology
Josephine Lembong, Benedikt Sabass, Howard Stone
The maintenance of tissue integrity is essential for the life of multicellular organisms. Healing of a skin wound is a paradigm for how various cell types localize and repair tissue perturbations in an orchestrated fashion. To investigate biophysical mechanisms associated with wound localization, we focus on a model system consisting of a fibroblast monolayer on an elastic substrate. We find that the creation of an edge in the monolayer causes cytosolic calcium oscillations throughout the monolayer. The oscillation frequency increases with cell density, which shows that wound-induced calcium oscillations occur collectively...
April 5, 2017: Physical Biology
Hamid Teimouri, Elgin Korkmazhan, Joel Stavans, Erel Levine
Small non-coding RNAs can exert significant regulatory activity on gene expression in bacteria. In recent years, substantial progress has been made in understanding bacterial gene expression by sRNAs. However, recent findings that demonstrate that families of mRNAs show non-trivial sub-cellular distributions raise the question of how localization may affect the regulatory activity of sRNAs. Here we address this question within a simple mathematical model. We show that the non-uniform spatial distributions of mRNA can alter the threshold-linear response that characterizes sRNAs that act stoichiometrically, and modulate the hierarchy among targets co-regulated by the same sRNA...
March 28, 2017: Physical Biology
Rob Johnson, Brian Munsky
Population modeling aims to capture and predict the dynamics of cell populations in constant or fluctuating environments. At the elementary level, population growth proceeds through sequential divisions of individual cells. Due to stochastic effects, populations of cells are inherently heterogeneous in phenotype, and some phenotypic variables have an effect on division or survival rates, as can be seen in partial drug resistance. Therefore, when modeling population dynamics where the control of growth and division is phenotype dependent, the corresponding model must take account of the underlying cellular heterogeneity...
May 11, 2017: Physical Biology
Thomas Blasi, Florian Buettner, Michael K Strasser, Carsten Marr, Fabian J Theis
Accessing gene expression at a single-cell level has unraveled often large heterogeneity among seemingly homogeneous cells, which remains obscured when using traditional population-based approaches. The computational analysis of single-cell transcriptomics data, however, still imposes unresolved challenges with respect to normalization, visualization and modeling the data. One such issue is differences in cell size, which introduce additional variability into the data and for which appropriate normalization techniques are needed...
May 11, 2017: Physical Biology
Victoria Tarle, Estelle Gauquelin, S R K Vedula, Joseph D'Alessandro, C T Lim, Benoit Ladoux, Nir S Gov
Monolayer expansion has generated great interest as a model system to study collective cell migration. During such an expansion the culture front often develops 'fingers', which we have recently modeled using a proposed feedback between the curvature of the monolayer's leading edge and the outward motility of the edge cells. We show that this model is able to explain the puzzling observed increase of collective cellular migration speed of a monolayer expanding into thin stripes, as well as describe the behavior within different confining geometries that were recently observed in experiments...
May 3, 2017: Physical Biology
David Pincus, Orna Resnekov, Kimberly A Reynolds
Allosteric regulation provides a way to control protein activity at the time scale of milliseconds to seconds inside the cell. An ability to engineer synthetic allosteric systems would be of practical utility for the development of novel biosensors, creation of synthetic cell signaling pathways, and design of small molecule pharmaceuticals with regulatory impact. To this end, we outline a general approach-termed rational engineering of allostery at conserved hotspots (REACH)-to introduce novel regulation into a protein of interest by exploiting latent allostery that has been hard-wired by evolution into its structure...
April 28, 2017: Physical Biology
Dolores Marín, Bartolomé Sabater
Cancer cells consume more glucose by glycolytic fermentation to lactate than by respiration, a characteristic known as the Warburg effect. In contrast with the 36 moles of ATP produced by respiration, fermentation produces two moles of ATP per mole of glucose consumed, which poses a puzzle with regard to the function of the Warburg effect. The production of free energy (ΔG), enthalpy (ΔH), and entropy (ΔS) per mole linearly varies with the fraction (x) of glucose consumed by fermentation that is frequently estimated around 0...
April 28, 2017: Physical Biology
R M Noest, Z Jane Wang
Tiger beetles pursue prey by adjusting their heading according to a time-delayed proportional control law that minimizes the error angle (Haselsteiner et al 2014 J. R. Soc. Interface 11 20140216). This control law can be further interpreted in terms of mechanical actuation: to catch prey, tiger beetles exert a sideways force by biasing their tripod gait in proportion to the error angle measured half a stride earlier. The proportional gain was found to be nearly optimal in the sense that it minimizes the time to point directly toward the prey...
April 20, 2017: Physical Biology
Eleanor C Ory, Lekhana Bhandary, Amanda E Boggs, Kristi R Chakrabarti, Joshua Parker, Wolfgang Losert, Stuart S Martin
The periphery of epithelial cells is shaped by opposing cytoskeletal physical forces generated predominately by two dynamic force generating systems-growing microtubule ends push against the boundary from the cell center, and the actin cortex contracts the attached plasma membrane. Here we investigate how changes to the structure and dynamics of the actin cortex alter the dynamics of microtubules. Current drugs target actin polymerization and contraction to reduce cell division and invasiveness; however, the impacts on microtubule dynamics remain incompletely understood...
April 20, 2017: Physical Biology
A V Paraskevov, D K Zendrikov
We show that in model neuronal cultures, where the probability of interneuronal connection formation decreases exponentially with increasing distance between the neurons, there exists a small number of spatial nucleation centers of a network spike, from where the synchronous spiking activity starts propagating in the network typically in the form of circular traveling waves. The number of nucleation centers and their spatial locations are unique and unchanged for a given realization of neuronal network but are different for different networks...
March 23, 2017: Physical Biology
Kien Nguyen, Paul Charles Whitford
For decades, protein folding and functional dynamics have been described in terms of diffusive motion across an underlying energy landscape. With continued advances in structural biology and high-performance computing, the field is positioned to extend these approaches to large biomolecular assemblies. Through the application of energy landscape techniques to the ribosome, one may work towards establishing a comprehensive description of the dynamics, which will bridge theoretical concepts and experimental observations...
March 22, 2017: Physical Biology
Eric E Keaveny, André E X Brown
A basic issue in the physics of behaviour is the mechanical relationship between an animal and its surroundings. The model nematode C. elegans provides an excellent platform to explore this relationship due to its anatomical simplicity. Nonetheless, the physics of nematode crawling, in which the worm undulates its body to move on a wet surface, is not completely understood and the mathematical models often used to describe this phenomenon are empirical. We confirm that linear resistive force theory, one such empirical model, is effective at predicting a worm's path from its sequence of body postures for forward crawling, reversing, and turning and for a broad range of different behavioural phenotypes observed in mutant worms...
March 22, 2017: Physical Biology
Peeyush Sahay, Pradeep K Shukla, Hemendra M Ghimire, Huda M Almabadi, Vibha Tripathi, Samarendra K Mohanty, Radhakrishna Rao, Prabhakar Pradhan
Chronic alcoholism is known to alter the morphology of the hippocampus, an important region of cognitive function in the brain. Therefore, to understand the effect of chronic alcoholism on hippocampal neural cells, we employed a mouse model of chronic alcoholism and quantified intranuclear nanoscale structural alterations in these cells. Transmission electron microscopy (TEM) images of hippocampal neurons were obtained, and the degree of structural alteration in terms of mass density fluctuation was determined using the light-localization properties of optical media generated from TEM imaging...
March 1, 2017: Physical Biology
M Schenkelberger, S Shanak, M Finkler, E G Worst, V Noireaux, V Helms, A Ott
Cytosine methylation plays an important role in the epigenetic regulation of eukaryotic gene expression. The methyl-CpG binding domain (MBD) is common to a family of eukaryotic transcriptional regulators. How MBD, a stretch of about 80 amino acids, recognizes CpGs in a methylation dependent manner, and as a function of sequence, is only partly understood. Here we show, using an Escherichia coli cell-free expression system, that MBD from the human transcriptional regulator MeCP2 performs as a specific, methylation-dependent repressor in conjunction with the BDNF (brain-derived neurotrophic factor) promoter sequence...
March 1, 2017: Physical Biology
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