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https://www.readbyqxmd.com/read/28714461/predicting-the-dynamics-of-bacterial-growth-inhibition-by-ribosome-targeting-antibiotics
#1
Philip Greulich, Jakub Dolezal, Matthew Scott, Martin R Evans, Rosalind J Allen
Understanding how antibiotics inhibit bacteria can help to reduce antibiotic use and hence avoid antimicrobial resistance - yet few theoretical models exist for bacterial growth inhibition by a clinically relevant antibiotic treatment regimen. In particular, in the clinic, antibiotic treatment is time-dependent. Here, we use a theoretical model, previously applied to steady-state bacterial growth, to predict the dynamical response of a bacterial cell to a time-dependent dose of ribosome-targeting antibiotic...
July 17, 2017: Physical Biology
https://www.readbyqxmd.com/read/28699625/mutation-supply-and-the-repeatability-of-selection-for-antibiotic-resistance
#2
Thomas van Dijk, Sungmin Hwang, Joachim Krug, Arjan Gm de Visser, Mark Peter Zwart
Whether evolution can be predicted is a key question in evolutionary biology. Here we set out to better understand the repeatability of evolution, which is a necessary condition for predictability. We explored experimentally the effect of mutation supply and the strength of selective pressure on the repeatability of selection from standing genetic variation. Different sizes of mutant libraries of antibiotic resistance gene TEM-1 β-lactamase in Escherichia coli, generated by error-prone PCR, were subjected to different antibiotic concentrations...
July 12, 2017: Physical Biology
https://www.readbyqxmd.com/read/28698411/estimation-of-turgor-pressure-through-comparison-between-single-plant-cell-and-pressurized-shell-mechanics
#3
Pauline Durand-Smet, Nicolas Chastrette, Estelle Gauquelin, Arezki Boudaoud, Atef Asnacios
While plant growth is well known to rely on turgor pressure, it is challenging to quantify the contribution of turgor pressure to plant cell rheology. Here we used a custom-made micro-rheometer to quantify the viscoelastic behavior of isolated plant cells while varying their internal turgor pressure. To get insight into how plant cells adapt their internal pressure to the osmolarity of their medium, we compared the mechanical behavior of single plant cells to that of a simple, passive, pressurized shell: a soccer ball...
July 12, 2017: Physical Biology
https://www.readbyqxmd.com/read/28675379/non-steady-state-mass-action-dynamics-without-rate-constants-dynamics-of-coupled-reactions-using-chemical-potentials
#4
William Cannon, Scott Baker
Comprehensive and predictive simulation of coupled reaction networks has long been a goal of biology and other fields. Currently, metabolic network models that utilize enzyme mass action kinetics have predictive power but are limited in scope and application by the fact that the determination of enzyme rate constants is laborious and low throughput. We present a statistical thermodynamic formulation of the law of mass action for coupled reactions at both steady states and non-stationary states. The formulation uses chemical potentials instead of rate constants...
July 4, 2017: Physical Biology
https://www.readbyqxmd.com/read/28649958/modeling-mechanical-interactions-in-growing-populations-of-rod-shaped-bacteria
#5
James Winkle, Oleg A Igoshin, Matthew Bennett, Kreso Josic, William Ott
Advances in synthetic biology allow us to engineer bacterial collectives with pre-specified characteristics. However, the behavior of these collectives is difficult to understand, as cellular growth and division as well as extra-cellular fluid flow lead to complex, changing arrangements of cells within the population. To rationally engineer and control the behavior of cell collectives we need theoretical and computational tools to understand their emergent spatiotemporal dynamics. Here, we present an agent-based model that allows growing cells to detect and respond to mechanical interactions...
June 26, 2017: Physical Biology
https://www.readbyqxmd.com/read/28635615/topography-on-a-subcellular-scale-modulates-cellular-adhesions-and-actin-stress-fiber-dynamics-in-tumor-associated-fibroblasts
#6
Mikheil Azatov, Xiaoyu Sun, Alexandra Suberi, John T Fourkas, Arpita Upadhyaya
Cells can sense and adapt to mechanical properties of their environment. The local geometry of the extracellular matrix, such as its topography, has been shown to modulate cell morphology, migration, and proliferation. Here we investigate the effect of micro/nanotopography on the morphology and cytoskeletal dynamics of human pancreatic tumor-associated fibroblast cells (TAFs). We use arrays of parallel nanoridges with variable spacings on a subcellular scale to investigate the response of TAFs to the topography of their environment...
June 21, 2017: Physical Biology
https://www.readbyqxmd.com/read/28656904/mapping-quorum-sensing-onto-neural-networks-to-understand-collective-decision-making-in-heterogeneous-microbial-communities
#7
Tahir I Yusufaly, James Q Boedicker
Microbial communities frequently communicate via quorum sensing (QS), where cells produce, secrete, and respond to a threshold level of an autoinducer (AI) molecule, thereby modulating gene expression. However, the biology of QS remains incompletely understood in heterogeneous communities, where variant bacterial strains possess distinct QS systems that produce chemically unique AIs. AI molecules bind to 'cognate' receptors, but also to 'non-cognate' receptors found in other strains, resulting in inter-strain crosstalk...
July 19, 2017: Physical Biology
https://www.readbyqxmd.com/read/28649977/convection-shapes-the-trade-off-between-antibiotic-efficacy-and-the-selection-for-resistance-in-spatial-gradients
#8
Matti Gralka, Diana Fusco, Stephen Martis, Oskar Hallatschek
Since penicillin was discovered about 90 years ago, we have become used to using drugs to eradicate unwanted pathogenic cells. However, using drugs to kill bacteria, viruses or cancer cells has the serious side effect of selecting for mutant types that survive the drug attack. A crucial question therefore is how one could eradicate as many cells as possible for a given acceptable risk of drug resistance evolution. We address this general question in a model of drug resistance evolution in spatial drug gradients, which recent experiments and theories have suggested as key drivers of drug resistance...
July 19, 2017: Physical Biology
https://www.readbyqxmd.com/read/28639563/the-role-of-apical-contractility-in-determining-cell-morphology-in-multilayered-epithelial-sheets-and-tubes
#9
Rui Zhen Tan, Tanny Lai, K-H Chiam
A multilayered epithelium is made up of individual cells that are stratified in an orderly fashion, layer by layer. In such tissues, individual cells can adopt a wide range of shapes ranging from columnar to squamous. From histological images, we observe that, in flat epithelia such as the skin, the cells in the top layer are squamous while those in the middle and bottom layers are columnar, whereas in tubular epithelia, the cells in all layers are columnar. We develop a computational model to understand how individual cell shape is governed by the mechanical forces within multilayered flat and curved epithelia...
July 19, 2017: Physical Biology
https://www.readbyqxmd.com/read/28510539/statistical-physics-approaches-to-subnetwork-dynamics-in-biochemical-systems
#10
B Bravi, P 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...
July 19, 2017: Physical Biology
https://www.readbyqxmd.com/read/28661893/exact-lower-and-upper-bounds-on-stationary-moments-in-stochastic-biochemical-systems
#11
Khem Raj Ghusinga, Cesar A Vargas-Garcia, Andrew Lamperski, Abhyudai Singh
In the stochastic description of biochemical reaction systems, the time evolution of statistical moments for species population counts is described by a linear dynamical system. However, except for some ideal cases (such as zero- and first-order reaction kinetics), the moment dynamics is underdetermined as lower-order moments depend upon higher-order moments. Here, we propose a novel method to find exact lower and upper bounds on stationary moments for a given arbitrary system of biochemical reactions. The method exploits the fact that statistical moments of any positive-valued random variable must satisfy some constraints that are compactly represented through the positive semidefiniteness of moment matrices...
June 29, 2017: Physical Biology
https://www.readbyqxmd.com/read/28597848/effects-of-soft-interactions-and-bound-mobility-on-diffusion-in-crowded-environments-a-model-of-sticky-and-slippery-obstacles
#12
Michael W Stefferson, Samantha L Norris, Franck J Vernerey, Meredith D Betterton, Loren E Hough
Crowded environments modify the diffusion of macromolecules, generally slowing their movement and inducing transient anomalous subdiffusion. The presence of obstacles also modifies the kinetics and equilibrium behavior of tracers. While previous theoretical studies of particle diffusion have typically assumed either impenetrable obstacles or binding interactions that immobilize the particle, in many cellular contexts bound particles remain mobile. Examples include membrane proteins or lipids with some entry and diffusion within lipid domains and proteins that can enter into membraneless organelles or compartments such as the nucleolus...
June 29, 2017: Physical Biology
https://www.readbyqxmd.com/read/28597843/dynamical-predictors-of-an-imminent-phenotypic-switch-in-bacteria
#13
Huijing Wang, J Christian J Ray
Single cells can stochastically switch across thresholds imposed by regulatory networks. Such thresholds can act as a tipping point, drastically changing global phenotypic states. In ecology and economics, imminent transitions across such tipping points can be predicted using dynamical early warning indicators. A typical example is 'flickering' of a fast variable, predicting a longer-lasting switch from a low to a high state or vice versa. Considering the different timescales between metabolite and protein fluctuations in bacteria, we hypothesized that metabolic early warning indicators predict imminent transitions across a network threshold caused by enzyme saturation...
June 29, 2017: Physical Biology
https://www.readbyqxmd.com/read/28585521/structural-evaluation-of-an-amyloid-fibril-model-using-small-angle-x-ray-scattering
#14
Eshan Dahal, Mina Choi, Nadia Alam, Ashwinkumar A Bhirde, Serge L Beaucage, Aldo Badano
Amyloid fibrils are highly structured protein aggregates associated with a wide range of diseases including Alzheimer's and Parkinson's. We report a structural investigation of an amyloid fibril model prepared from a commonly used plasma protein (bovine serum albumin (BSA)) using small-angle x-ray scattering (SAXS) technique. As a reference, the size estimates from SAXS are compared to dynamic light scattering (DLS) data and the presence of amyloid-like fibrils is confirmed using Congo red absorbance assay...
June 29, 2017: Physical Biology
https://www.readbyqxmd.com/read/28656905/probing-cooperative-force-generation-in-collective-cancer-invasion
#15
Amani A Alobaidi, Yaopengxiao Xu, Shaohua Chen, Yang Jiao, Bo Sun
Collective cellular dynamics in the three-dimensional extracellular matrix (ECM) plays a crucial role in many physiological processes such as cancer invasion. Both chemical and mechanical signaling support cell-cell communications on a variety of length scales, leading to collective migratory behaviors. Here we conduct experiments using 3D in vitro tumor models and develop a phenomenological model in order to probe the cooperativity of force generation in the collective invasion of breast cancer cells. In our model, cell-cell communication is characterized by a single parameter that quantifies the correlation length of cellular migration cycles...
June 28, 2017: Physical Biology
https://www.readbyqxmd.com/read/28617678/single-variant-bottleneck-in-the-early-dynamics-of-h-influenzae-bacteremia-in-neonatal-rats-questions-the-theory-of-independent-action
#16
Xinxian Shao, Bruce Levin, Ilya Nemenman
There is an abundance of information about the genetic basis, physiological and molecular mechanisms of bacterial pathogenesis. In contrast, relatively little is known about population dynamic processes, by which bacteria colonize hosts and invade tissues and cells and thereby cause disease. In an article published in 1978, Moxon and Murphy presented evidence that, when inoculated intranasally with a mixture streptomycin sensitive and resistant (Sm (S) and Sm (R) ) and otherwise isogenic strains of Haemophilus influenzae type b (Hib), neonatal rats develop a bacteremic infection that often is dominated by only one strain, Sm (S) or Sm (R) ...
June 15, 2017: Physical Biology
https://www.readbyqxmd.com/read/28510537/converging-evolution-leads-to-near-maximal-junction-diversity-through-parallel-mechanisms-in-b-and-t-cell-receptors
#17
Jennifer I C Benichou, Jeroen W J van 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 emerges as to whether they can produce a diverse CDR3 repertoire. In order to address the genetic diversity of the adaptive immune system, appropriate quantitative measures for diversity and large-scale sequencing are required...
June 15, 2017: Physical Biology
https://www.readbyqxmd.com/read/28586319/rev-erb-and-ror-therapeutic-targets-for-treating-myopathies
#18
REVIEW
Ryan D Welch, Colin A Flaveny
Muscle is primarily known for its mechanical roles in locomotion, maintenance of posture, and regulation of cardiac and respiratory function. There are numerous medical conditions that adversely affect muscle, myopathies that disrupt muscle development, regeneration and protein turnover to detrimental effect. Skeletal muscle is also a vital secretory organ that regulates thermogenesis, inflammatory signaling and directs context specific global metabolic changes in energy substrate preference on a daily basis...
June 6, 2017: Physical Biology
https://www.readbyqxmd.com/read/28586314/microrna-mediated-regulatory-circuits-outlook-and-perspectives
#19
REVIEW
Davide Cora', Angela Re, Michele Caselle, Federico Bussolino
MicroRNAs have been found to be necessary for regulating genes implicated in almost all signaling pathways, and consequently their dysfunction influences many diseases, including cancer. Understanding of the complexity of the microRNA-mediated regulatory network has grown in terms of size, connectivity and dynamics with the development of computational and, more recently, experimental high-throughput approaches for microRNA target identification. Newly developed studies on recurrent microRNA-mediated circuits in regulatory networks, also known as network motifs, have substantially contributed to addressing this complexity, and therefore to helping understand the ways by which microRNAs achieve their regulatory role...
June 6, 2017: Physical Biology
https://www.readbyqxmd.com/read/28586313/physical-insights-into-the-blood-brain-barrier-translocation-mechanisms
#20
REVIEW
Panagiotis E Theodorakis, Erich A Müller, Richard V Craster, Omar K Matar
The number of individuals suffering from diseases of the central nervous system (CNS) is growing with an aging population. While candidate drugs for many of these diseases are available, most of these pharmaceutical agents cannot reach the brain rendering most of the drug therapies that target the CNS inefficient. The reason is the blood-brain barrier (BBB), a complex and dynamic interface that controls the influx and efflux of substances through a number of different translocation mechanisms. Here, we present these mechanisms providing, also, the necessary background related to the morphology and various characteristics of the BBB...
June 6, 2017: Physical Biology
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