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0704.0021
Yuichi Togashi
Vanessa Casagrande, Yuichi Togashi, Alexander S. Mikhailov
Molecular Synchronization Waves in Arrays of Allosterically Regulated Enzymes
5 pages, 4 figures
Phys. Rev. Lett. 99, 048301 (2007)
10.1103/PhysRevLett.99.048301
null
nlin.PS physics.chem-ph q-bio.MN
null
Spatiotemporal pattern formation in a product-activated enzymic reaction at high enzyme concentrations is investigated. Stochastic simulations show that catalytic turnover cycles of individual enzymes can become coherent and that complex wave patterns of molecular synchronization can develop. The analysis based on the mean-field approximation indicates that the observed patterns result from the presence of Hopf and wave bifurcations in the considered system.
2007-07-24
0704.0034
Vasily Ogryzko V
Vasily Ogryzko
Origin of adaptive mutants: a quantum measurement?
5 pages
null
null
null
q-bio.PE q-bio.CB quant-ph
null
This is a supplement to the paper arXiv:q-bio/0701050, containing the text of correspondence sent to Nature in 1990.
2007-05-23
0704.0036
Eduardo D. Sontag
Liming Wang and Eduardo D. Sontag
A remark on the number of steady states in a multiple futile cycle
Resubmit with new results on the upper bound of the number of steady states. 20 pages, 2 figures, See http://www.math.rutgers.edu/~sontag/PUBDIR/index.html for online preprints and reprints of related work
null
null
null
q-bio.QM q-bio.MN
null
The multisite phosphorylation-dephosphorylation cycle is a motif repeatedly used in cell signaling. This motif itself can generate a variety of dynamic behaviors like bistability and ultrasensitivity without direct positive feedbacks. In this paper, we study the number of positive steady states of a general multisite phosphorylation-dephosphorylation cycle, and how the number of positive steady states varies by changing the biological parameters. We show analytically that (1) for some parameter ranges, there are at least n+1 (if n is even) or n (if n is odd) steady states; (2) there never are more than 2n-1 steady states (in particular, this implies that for n=2, including single levels of MAPK cascades, there are at most three steady states); (3) for parameters near the standard Michaelis-Menten quasi-steady state conditions, there are at most n+1 steady states; and (4) for parameters far from the standard Michaelis-Menten quasi-steady state conditions, there is at most one steady state.
2011-11-09
0704.0158
Huijie Yang
Fangcui Zhao, Huijie Yang, and Binghong Wang
Complexities of Human Promoter Sequences
5 pages, 3 figures, To appear in Journal of Theoretical Biology
Journal of Theoretical Biology 247 (2007) 645?C649
10.1016/j.jtbi.2007.03.035
null
q-bio.OT
null
By means of the diffusion entropy approach, we detect the scale-invariance characteristics embedded in the 4737 human promoter sequences. The exponent for the scale-invariance is in a wide range of $[ {0.3,0.9} ]$, which centered at $\delta_c = 0.66$. The distribution of the exponent can be separated into left and right branches with respect to the maximum. The left and right branches are asymmetric and can be fitted exactly with Gaussian form with different widths, respectively.
2011-11-09
0704.0191
Peter Virnau
Peter Virnau (1), Leonid A. Mirny (1,2), Mehran Kardar (1) ((1) Massachusetts Institute of Technology, Department of Physics, Cambridge, MA, United States of America, (2) Massachusetts Institute of Technology, Harvard-MIT Division of Health Science and Technology, Cambridge, MA, United States of America)
Intricate Knots in Proteins: Function and Evolution
6 pages, 2 figures, 1 table
P. Virnau, L. A. Mirny, M. Kardar, PLoS Comp Biol 2, 1074-1079 (2006)
null
null
physics.bio-ph physics.data-an q-bio.BM
null
A number of recently discovered protein structures incorporate a rather unexpected structural feature: a knot in the polypeptide backbone. These knots are extremely rare, but their occurrence is likely connected to protein function in as yet unexplored fashion. Our analysis of the complete Protein Data Bank reveals several new knots which, along with previously discovered ones, can shed light on such connections. In particular, we identify the most complex knot discovered to date in human ubiquitin hydrolase, and suggest that its entangled topology protects it against unfolding and degradation by the proteasome. Knots in proteins are typically preserved across species and sometimes even across kingdoms. However, we also identify a knot which only appears in some transcarbamylases while being absent in homologous proteins of similar structure. The emergence of the knot is accompanied by a shift in the enzymatic function of the protein. We suggest that the simple insertion of a short DNA fragment into the gene may suffice to turn an unknotted into a knotted structure in this protein.
2007-05-23
0704.0271
Edgardo Brigatti
E. Brigatti, V. Schwammle and Minos A. Neto
An individual based model with global competition interaction: fluctuations effects in pattern formation
9 pages, 9 figures, minor changes
Physical Review E 77, 021914 (2008)
10.1103/PhysRevE.77.021914
null
cond-mat.stat-mech q-bio.PE
null
We present some numerical results obtained from a simple individual based model that describes clustering of organisms caused by competition. Our aim is to show how, even when a deterministic description developed for continuum models predicts no pattern formation, an individual based model displays well defined patterns, as a consequence of fluctuations effects caused by the discrete nature of the interacting agents.
2009-11-13
0704.0304
Carlos Gershenson
Carlos Gershenson
The World as Evolving Information
16 pages. Extended version, three more laws of information, two classifications, and discussion added. To be published (soon) in International Conference on Complex Systems 2007 Proceedings
Minai, A., Braha, D., and Bar-Yam, Y., eds. Unifying Themes in Complex Systems VII, pp. 100-115. Springer, Berlin Heidelberg, 2012
10.1007/978-3-642-18003-3_10
null
cs.IT cs.AI math.IT q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
This paper discusses the benefits of describing the world as information, especially in the study of the evolution of life and cognition. Traditional studies encounter problems because it is difficult to describe life and cognition in terms of matter and energy, since their laws are valid only at the physical scale. However, if matter and energy, as well as life and cognition, are described in terms of information, evolution can be described consistently as information becoming more complex. The paper presents eight tentative laws of information, valid at multiple scales, which are generalizations of Darwinian, cybernetic, thermodynamic, psychological, philosophical, and complexity principles. These are further used to discuss the notions of life, cognition and their evolution.
2013-04-05
0704.0305
Yongxing Guo
Yongxing Guo, Yifeng Liu, Jay X. Tang, and James M. Valles Jr
Polymerization Force Driven Buckling of Microtubule Bundles Determines the Wavelength of Patterns Formed in Tubulin Solutions
4 pages, 4 figures
Phys. Rev. Lett. 98, 198103 (2007)
10.1103/PhysRevLett.98.198103
null
physics.bio-ph
null
We present a model for the spontaneous formation of a striated pattern in polymerizing microtubule solutions. It describes the buckling of a single microtubule (MT) bundle within an elastic network formed by other similarly aligned and buckling bundles and unaligned MTs. Phase contrast and polarization microscopy studies of the temporal evolution of the pattern imply that the polymerization of MTs within the bundles creates the driving compressional force. Using the measured rate of buckling, the established MT force-velocity curve and the pattern wavelength, we obtain reasonable estimates for the MT bundle bending rigidity and the elastic constant of the network. The analysis implies that the bundles buckle as solid rods.
2007-06-13
0704.0322
Liu Quanxing
Quan-Xing Liu, Gui-Quan Sun, Bai-Lian Li and Zhen Jin
Emergence of spatiotemporal chaos driven by far-field breakup of spiral waves in the plankton ecological systems
9 Figures and 11 pages, REVTeX 4
2009 Chinese Phys. B 18 506-515
10.1088/1674-1056/18/2/021
null
nlin.PS nlin.CD q-bio.PE
null
Alexander B. Medvinsky \emph{et al} [A. B. Medvinsky, I. A. Tikhonova, R. R. Aliev, B.-L. Li, Z.-S. Lin, and H. Malchow, Phys. Rev. E \textbf{64}, 021915 (2001)] and Marcus R. Garvie \emph{et al} [M. R. Garvie and C. Trenchea, SIAM J. Control. Optim. \textbf{46}, 775-791 (2007)] shown that the minimal spatially extended reaction-diffusion model of phytoplankton-zooplankton can exhibit both regular, chaotic behavior, and spatiotemporal patterns in a patchy environment. Based on that, the spatial plankton model is furtherly investigated by means of computer simulations and theoretical analysis in the present paper when its parameters would be expected in the case of mixed Turing-Hopf bifurcation region. Our results show that the spiral waves exist in that region and the spatiotemporal chaos emerge, which arise from the far-field breakup of the spiral waves over large ranges of diffusion coefficients of phytoplankton and zooplankton. Moreover, the spatiotemporal chaos arising from the far-field breakup of spiral waves does not gradually involve the whole space within that region. Our results are confirmed by means of computation spectra and nonlinear bifurcation of wave trains. Finally, we give some explanations about the spatially structured patterns from the community level.
2009-05-29
0704.0331
C. Soule
J.-L. Jestin, C. Soule (IHES)
Symmetries by base substitutions in the genetic code predict 2' or 3' aminoacylation of tRNAs
Accepted for publication in the Journal of Theoretical Biology
null
null
null
q-bio.OT
null
This letter reports complete sets of two-fold symmetries between partitions of the universal genetic code. By substituting bases at each position of the codons according to a fixed rule, it happens that properties of the degeneracy pattern or of tRNA aminoacylation specificity are exchanged.
2007-05-23
0704.0357
Gergely J Sz\"oll\H{o}si
Gergely J Szollosi and Imre Derenyi
Evolutionary games on minimally structured populations
Supporting information available as EPAPS Document No. E-PLEEE8-78-144809 at http://ftp.aip.org/epaps/phys_rev_e/E-PLEEE8-78-144809/
PHYSICAL REVIEW E 78, 031919 (2008)
10.1103/PhysRevE.78.031919
null
q-bio.PE q-bio.OT
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
Population structure induced by both spatial embedding and more general networks of interaction, such as model social networks, have been shown to have a fundamental effect on the dynamics and outcome of evolutionary games. These effects have, however, proved to be sensitive to the details of the underlying topology and dynamics. Here we introduce a minimal population structure that is described by two distinct hierarchical levels of interaction. We believe this model is able to identify effects of spatial structure that do not depend on the details of the topology. We derive the dynamics governing the evolution of a system starting from fundamental individual level stochastic processes through two successive meanfield approximations. In our model of population structure the topology of interactions is described by only two parameters: the effective population size at the local scale and the relative strength of local dynamics to global mixing. We demonstrate, for example, the existence of a continuous transition leading to the dominance of cooperation in populations with hierarchical levels of unstructured mixing as the benefit to cost ratio becomes smaller then the local population size. Applying our model of spatial structure to the repeated prisoner's dilemma we uncover a novel and counterintuitive mechanism by which the constant influx of defectors sustains cooperation. Further exploring the phase space of the repeated prisoner's dilemma and also of the "rock-paper-scissor" game we find indications of rich structure and are able to reproduce several effects observed in other models with explicit spatial embedding, such as the maintenance of biodiversity and the emergence of global oscillations.
2009-11-13
0704.0392
Marcus Kaiser
Marcus Kaiser, Robert Martin, Peter Andras and Malcolm P. Young
Simulation of Robustness against Lesions of Cortical Networks
submitted to European Journal of Neuroscience (under review)
European Journal of Neuroscience, 25:3185--3192, 2007
10.1111/j.1460-9568.2007.05574.x
null
q-bio.NC cond-mat.dis-nn physics.soc-ph
null
Structure entails function and thus a structural description of the brain will help to understand its function and may provide insights into many properties of brain systems, from their robustness and recovery from damage, to their dynamics and even their evolution. Advances in the analysis of complex networks provide useful new approaches to understanding structural and functional properties of brain networks. Structural properties of networks recently described allow their characterization as small-world, random (exponential) and scale-free. They complement the set of other properties that have been explored in the context of brain connectivity, such as topology, hodology, clustering, and hierarchical organization. Here we apply new network analysis methods to cortical inter-areal connectivity networks for the cat and macaque brains. We compare these corticocortical fibre networks to benchmark rewired, small-world, scale-free and random networks, using two analysis strategies, in which we measure the effects of the removal of nodes and connections on the structural properties of the cortical networks. The brain networks' structural decay is in most respects similar to that of scale-free networks. The results implicate highly connected hub-nodes and bottleneck connections as structural basis for some of the conditional robustness of brain systems. This informs the understanding of the development of brain networks' connectivity.
2008-08-27
0704.0429
Ping Ao
P. Ao
Quantitative Resolution to some "Absolute Discrepancies" in Cancer Theories: a View from Phage lambda Genetic Switch
latex, 7 pages
CellularOncology29:67-69,2007
null
null
q-bio.SC q-bio.CB
null
Is it possible to understand cancer? Or more specifically, is it possible to understand cancer from genetic side? There already many answers in literature. The most optimistic one has claimed that it is mission-possible. Duesberg and his colleagues reviewed the impressive amount of research results on cancer accumulated over 100 years. It confirms the a general opinion that considering all available experimental results and clinical observations there is no cancer theory without major difficulties, including the prevailing gene-based cancer theories. They have then listed 9 "absolute discrepancies" for such cancer theory. In this letter the quantitative evidence against one of their major reasons for dismissing mutation cancer theory, by both in vivo experiment and a first principle computation, is explicitly pointed out.
2008-11-26
0704.0464
Edward Lyman Ph.D.
Edward Lyman and Daniel M. Zuckerman
Annealed importance sampling of dileucine peptide
null
null
10.1063/1.2754267
null
q-bio.BM
null
Annealed importance sampling is a means to assign equilibrium weights to a nonequilibrium sample that was generated by a simulated annealing protocol. The weights may then be used to calculate equilibrium averages, and also serve as an ``adiabatic signature'' of the chosen cooling schedule. In this paper we demonstrate the method on the 50-atom dileucine peptide, showing that equilibrium distributions are attained for manageable cooling schedules. For this system, as naively implemented here, the method is modestly more efficient than constant temperature simulation. However, the method is worth considering whenever any simulated heating or cooling is performed (as is often done at the beginning of a simulation project, or during an NMR structure calculation), as it is simple to implement and requires minimal additional CPU expense. Furthermore, the naive implementation presented here can be improved.
2009-11-13
0704.0598
Ignazio Licata
Ignazio Licata, Luigi Lella
Evolutionary Neural Gas (ENG): A Model of Self Organizing Network from Input Categorization
16 pages, 8 figures
EJTP,vol.4,, No.14 (2007),31-50
null
null
physics.gen-ph q-bio.PE
null
Despite their claimed biological plausibility, most self organizing networks have strict topological constraints and consequently they cannot take into account a wide range of external stimuli. Furthermore their evolution is conditioned by deterministic laws which often are not correlated with the structural parameters and the global status of the network, as it should happen in a real biological system. In nature the environmental inputs are noise affected and fuzzy. Which thing sets the problem to investigate the possibility of emergent behaviour in a not strictly constrained net and subjected to different inputs. It is here presented a new model of Evolutionary Neural Gas (ENG) with any topological constraints, trained by probabilistic laws depending on the local distortion errors and the network dimension. The network is considered as a population of nodes that coexist in an ecosystem sharing local and global resources. Those particular features allow the network to quickly adapt to the environment, according to its dimensions. The ENG model analysis shows that the net evolves as a scale-free graph, and justifies in a deeply physical sense- the term gas here used.
2010-04-26
0704.0615
Trevor Bruen TB
Trevor Bruen, David Bryant
Parsimony via concensus
Final published version of article
Systematic Biology (2008), 57(2): 251-56
10.1080/10635150802040597
null
q-bio.PE
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The parsimony score of a character on a tree equals the number of state changes required to fit that character onto the tree. We show that for unordered, reversible characters this score equals the number of tree rearrangements required to fit the tree onto the character. We discuss implications of this connection for the debate over the use of consensus trees or total evidence, and show how it provides a link between incongruence of characters and recombination.
2013-10-02
0704.0634
Mark Bathe
Mark Bathe
A Finite Element framework for computation of protein normal modes and mechanical response
null
null
null
null
q-bio.BM q-bio.QM
null
A coarse-grained computational procedure based on the Finite Element Method is proposed to calculate the normal modes and mechanical response of proteins and their supramolecular assemblies. Motivated by the elastic network model, proteins are modeled as homogeneous isotropic elastic solids with volume defined by their solvent-excluded surface. The discretized Finite Element representation is obtained using a surface simplification algorithm that facilitates the generation of models of arbitrary prescribed spatial resolution. The procedure is applied to compute the normal modes of a mutant of T4 phage lysozyme and of filamentous actin, as well as the critical Euler buckling load of the latter when subject to axial compression. Results compare favorably with all-atom normal mode analysis, the Rotation Translation Blocks procedure, and experiment. The proposed methodology establishes a computational framework for the calculation of protein mechanical response that facilitates the incorporation of specific atomic-level interactions into the model, including aqueous-electrolyte-mediated electrostatic effects. The procedure is equally applicable to proteins with known atomic coordinates as it is to electron density maps of proteins, protein complexes, and supramolecular assemblies of unknown atomic structure.
2007-05-23
0704.0648
Kaushik Majumdar
Kaushik Majumdar
Behavioral response to strong aversive stimuli: A neurodynamical model
Submitted to journal
null
null
null
q-bio.NC
null
In this paper a theoretical model of functioning of a neural circuit during a behavioral response has been proposed. A neural circuit can be thought of as a directed multigraph whose each vertex is a neuron and each edge is a synapse. It has been assumed in this paper that the behavior of such circuits is manifested through the collective behavior of neurons belonging to that circuit. Behavioral information of each neuron is contained in the coefficients of the fast Fourier transform (FFT) over the output spike train. Those coefficients form a vector in a multidimensional vector space. Behavioral dynamics of a neuronal network in response to strong aversive stimuli has been studied in a vector space in which a suitable pseudometric has been defined. The neurodynamical model of network behavior has been formulated in terms of existing memory, synaptic plasticity and feelings. The model has an analogy in classical electrostatics, by which the notion of force and potential energy has been introduced. Since the model takes input from each neuron in a network and produces a behavior as the output, it would be extremely difficult or may even be impossible to implement. But with the help of the model a possible explanation for an hitherto unexplained neurological observation in human brain has been offered. The model is compatible with a recent model of sequential behavioral dynamics. The model is based on electrophysiology, but its relevance to hemodynamics has been outlined.
2007-05-23
0704.0673
Mark McDonnell
Mark D. McDonnell, Nigel G. Stocks and Derek Abbott
Optimal stimulus and noise distributions for information transmission via suprathreshold stochastic resonance
Accepted for publication by Physical Review E, 28 pages of text and references, 5 figures, 2 tables
Phys. Rev. E 75, 061105 (2007)
10.1103/PhysRevE.75.061105
null
cond-mat.stat-mech q-bio.NC
null
Suprathreshold stochastic resonance (SSR) is a form of noise enhanced signal transmission that occurs in a parallel array of independently noisy identical threshold nonlinearities, including model neurons. Unlike most forms of stochastic resonance, the output response to suprathreshold random input signals of arbitrary magnitude is improved by the presence of even small amounts of noise. In this paper the information transmission performance of SSR in the limit of a large array size is considered. Using a relationship between Shannon's mutual information and Fisher information, a sufficient condition for optimality, i.e. channel capacity, is derived. It is shown that capacity is achieved when the signal distribution is Jeffrey's prior, as formed from the noise distribution, or when the noise distribution depends on the signal distribution via a cosine relationship. These results provide theoretical verification and justification for previous work in both computational neuroscience and electronics.
2007-07-02
0704.1147
Giulio Ruffini
Giulio Ruffini
Information, complexity, brains and reality (Kolmogorov Manifesto)
This is a live essay, kind of a mental log book on a series of topics under the theme of information and compression
null
null
Starlab TN00054
physics.gen-ph physics.bio-ph
null
I discuss several aspects of information theory and its relationship to physics and neuroscience. The unifying thread of this somewhat chaotic essay is the concept of Kolmogorov or algorithmic complexity (Kolmogorov Complexity, for short). I argue that it is natural to interpret cognition as the art of finding algorithms that apprach the Solomonoff-Kolmogorov-Chaitin (algorithmic) Complexity limit with appropriate tradeoffs. In addition, I claim that what we call the universe is an interpreted abstraction--a mental construct--based on the observed coherence between multiple sensory input streams and our own interactions. Hence, the notion of Universe is itself a model.
2007-05-23
0704.1169
Dirson Jian Li
Dirson Jian Li, Shengli Zhang
Holographic bound and protein linguistics
4 pages, 4 figures. A trial application of holographic bound in life science
null
null
null
q-bio.GN hep-th q-bio.QM
null
The holographic bound in physics constrains the complexity of life. The finite storage capability of information in the observable universe requires the protein linguistics in the evolution of life. We find that the evolution of genetic code determines the variance of amino acid frequencies and genomic GC content among species. The elegant linguistic mechanism is confirmed by the experimental observations based on all known entire proteomes.
2007-05-23
0704.1362
J.H. van Hateren
J. H. van Hateren
Fast recursive filters for simulating nonlinear dynamic systems
20 pages, 8 figures, 1 table. A comparison with 4th-order Runge-Kutta integration shows that the new algorithm is 1-2 orders of magnitude faster. The paper is in press now at Neural Computation
Neural Computation 20:1821-1846 (2008)
null
null
q-bio.QM q-bio.NC
null
A fast and accurate computational scheme for simulating nonlinear dynamic systems is presented. The scheme assumes that the system can be represented by a combination of components of only two different types: first-order low-pass filters and static nonlinearities. The parameters of these filters and nonlinearities may depend on system variables, and the topology of the system may be complex, including feedback. Several examples taken from neuroscience are given: phototransduction, photopigment bleaching, and spike generation according to the Hodgkin-Huxley equations. The scheme uses two slightly different forms of autoregressive filters, with an implicit delay of zero for feedforward control and an implicit delay of half a sample distance for feedback control. On a fairly complex model of the macaque retinal horizontal cell it computes, for a given level of accuracy, 1-2 orders of magnitude faster than 4th-order Runge-Kutta. The computational scheme has minimal memory requirements, and is also suited for computation on a stream processor, such as a GPU (Graphical Processing Unit).
2008-06-20
0704.1390
Azam Gholami
Azam Gholami, Martin Falcke, Erwin Frey
Velocity oscillations in actin-based motility
5 pages, 6 figures
null
10.1088/1367-2630/10/3/033022
HMI 18779, LMU-ASC 18/07
q-bio.CB
null
We present a simple and generic theoretical description of actin-based motility, where polymerization of filaments maintains propulsion. The dynamics is driven by polymerization kinetics at the filaments' free ends, crosslinking of the actin network, attachment and detachment of filaments to the obstacle interfaces and entropic forces. We show that spontaneous oscillations in the velocity emerge in a broad range of parameter values, and compare our findings with experiments.
2015-05-13
0704.1546
Richard A Neher
Richard A. Neher, Wolfram Mobius, Erwin Frey, Ulrich Gerland
Optimal flexibility for conformational transitions in macromolecules
4 pages, 4 figures
null
10.1103/PhysRevLett.99.178101
LMU-ASC 22/07
q-bio.BM
null
Conformational transitions in macromolecular complexes often involve the reorientation of lever-like structures. Using a simple theoretical model, we show that the rate of such transitions is drastically enhanced if the lever is bendable, e.g. at a localized "hinge''. Surprisingly, the transition is fastest with an intermediate flexibility of the hinge. In this intermediate regime, the transition rate is also least sensitive to the amount of "cargo'' attached to the lever arm, which could be exploited by molecular motors. To explain this effect, we generalize the Kramers-Langer theory for multi-dimensional barrier crossing to configuration dependent mobility matrices.
2009-11-13
0704.1547
Martin Castelnovo
Fabien Montel, Emeline Fontaine, Philippe St-Jean, Martin Castelnovo, Cendrine Moskalenko-Faivre
AFM Imaging of SWI/SNF action: mapping the nucleosome remodeling and sliding
25 pages,5 figures, to appear in Biophysical Journal
null
10.1529/biophysj.107.105569
null
physics.bio-ph cond-mat.soft q-bio.BM
null
We propose a combined experimental (Atomic Force Microscopy) and theoretical study of the structural and dynamical properties of nucleosomes. In contrast to biochemical approaches, this method allows to determine simultaneously the DNA complexed length distribution and nucleosome position in various contexts. First, we show that differences in the nucleo-proteic structure observed between conventional H2A and H2A.Bbd variant nucleosomes induce quantitative changes in the in the length distribution of DNA complexed with histones. Then, the sliding action of remodeling complex SWI/SNF is characterized through the evolution of the nucleosome position and wrapped DNA length mapping. Using a linear energetic model for the distribution of DNA complexed length, we extract the net wrapping energy of DNA onto the histone octamer, and compare it to previous studies.
2009-11-13
0704.1571
Philippe Gambette
Philippe Gambette (LIAFA), St\'ephane Vialette (LRI)
On restrictions of balanced 2-interval graphs
null
Dans Lecture Notes In Computer Science - 33rd International Workshop on Graph-Theoretic Concepts in Computer Science (WG'07), Dornburg : Allemagne (2007)
10.1007/978-3-540-74839-7_6
null
cs.DM q-bio.QM
null
The class of 2-interval graphs has been introduced for modelling scheduling and allocation problems, and more recently for specific bioinformatic problems. Some of those applications imply restrictions on the 2-interval graphs, and justify the introduction of a hierarchy of subclasses of 2-interval graphs that generalize line graphs: balanced 2-interval graphs, unit 2-interval graphs, and (x,x)-interval graphs. We provide instances that show that all the inclusions are strict. We extend the NP-completeness proof of recognizing 2-interval graphs to the recognition of balanced 2-interval graphs. Finally we give hints on the complexity of unit 2-interval graphs recognition, by studying relationships with other graph classes: proper circular-arc, quasi-line graphs, K_{1,5}-free graphs, ...
2008-02-04
0704.1667
Erel Levine
Erel Levine and Terence Hwa
Stochastic fluctuations in metabolic pathways
null
PNAS 2007
10.1073/pnas.0610987104
null
q-bio.MN cond-mat.stat-mech
null
Fluctuations in the abundance of molecules in the living cell may affect its growth and well being. For regulatory molecules (e.g., signaling proteins or transcription factors), fluctuations in their expression can affect the levels of downstream targets in a network. Here, we develop an analytic framework to investigate the phenomenon of noise correlation in molecular networks. Specifically, we focus on the metabolic network, which is highly inter-linked, and noise properties may constrain its structure and function. Motivated by the analogy between the dynamics of a linear metabolic pathway and that of the exactly soluable linear queueing network or, alternatively, a mass transfer system, we derive a plethora of results concerning fluctuations in the abundance of intermediate metabolites in various common motifs of the metabolic network. For all but one case examined, we find the steady-state fluctuation in different nodes of the pathways to be effectively uncorrelated. Consequently, fluctuations in enzyme levels only affect local properties and do not propagate elsewhere into metabolic networks, and intermediate metabolites can be freely shared by different reactions. Our approach may be applicable to study metabolic networks with more complex topologies, or protein signaling networks which are governed by similar biochemical reactions. Possible implications for bioinformatic analysis of metabolimic data are discussed.
2009-11-13
0704.1672
Ilia Solov'yov
Ilia A. Solov'yov, Alexander V. Yakubovich, Andrey V. Solov'yov and Walter Greiner
Two center multipole expansion method: application to macromolecular systems
23 pages, 7 figures, 1 table
null
10.1103/PhysRevE.75.051912
null
physics.bio-ph physics.comp-ph
null
We propose a new theoretical method for the calculation of the interaction energy between macromolecular systems at large distances. The method provides a linear scaling of the computing time with the system size and is considered as an alternative to the well known fast multipole method. Its efficiency, accuracy and applicability to macromolecular systems is analyzed and discussed in detail.
2009-11-13
0704.1763
Ilia Solov'yov
Ilia A. Solov'yov, Walter Greiner
Towards understanding of birds magnetoreceptor mechanism
10 pages, 4 figures
null
null
null
physics.bio-ph
null
In the present letter we suggest a new theoretical model for a quantitative description of the magnetoreception mechanism in birds. The considered mechanism involves two types of iron minerals (magnetite and maghemite) which were found in subcellular compartments within sensory dendrites of the upper beak of several bird species. The analysis of forces acting between the iron particles shows that the orientation of the external geomagnetic field can significantly change the probability of the mechanosensitive ion channels opening and closing. The performed theoretical analysis shows that the suggested magnetoreceptor system might be a sensitive biological magnetometer providing an essential part of the magnetic map for navigation.
2007-05-23
0704.1811
Samarth Swarup
Samarth Swarup and Les Gasser
Unifying Evolutionary and Network Dynamics
11 pages, 12 figures, Accepted for publication in Physical Review E
null
10.1103/PhysRevE.75.066114
null
q-bio.QM q-bio.PE
null
Many important real-world networks manifest "small-world" properties such as scale-free degree distributions, small diameters, and clustering. The most common model of growth for these networks is "preferential attachment", where nodes acquire new links with probability proportional to the number of links they already have. We show that preferential attachment is a special case of the process of molecular evolution. We present a new single-parameter model of network growth that unifies varieties of preferential attachment with the quasispecies equation (which models molecular evolution), and also with the Erdos-Renyi random graph model. We suggest some properties of evolutionary models that might be applied to the study of networks. We also derive the form of the degree distribution resulting from our algorithm, and we show through simulations that the process also models aspects of network growth. The unification allows mathematical machinery developed for evolutionary dynamics to be applied in the study of network dynamics, and vice versa.
2009-11-13
0704.1885
Jesse Bloom
Jesse D. Bloom, Zhongyi Lu, David Chen, Alpan Raval, Ophelia S. Venturelli, and Frances H. Arnold
Evolution favors protein mutational robustness in sufficiently large populations
null
BMC Biology 5:29 (2007)
10.1186/1741-7007-5-29
null
q-bio.PE q-bio.BM
null
BACKGROUND: An important question is whether evolution favors properties such as mutational robustness or evolvability that do not directly benefit any individual, but can influence the course of future evolution. Functionally similar proteins can differ substantially in their robustness to mutations and capacity to evolve new functions, but it has remained unclear whether any of these differences might be due to evolutionary selection for these properties. RESULTS: Here we use laboratory experiments to demonstrate that evolution favors protein mutational robustness if the evolving population is sufficiently large. We neutrally evolve cytochrome P450 proteins under identical selection pressures and mutation rates in populations of different sizes, and show that proteins from the larger and thus more polymorphic population tend towards higher mutational robustness. Proteins from the larger population also evolve greater stability, a biophysical property that is known to enhance both mutational robustness and evolvability. The excess mutational robustness and stability is well described by existing mathematical theories, and can be quantitatively related to the way that the proteins occupy their neutral network. CONCLUSIONS: Our work is the first experimental demonstration of the general tendency of evolution to favor mutational robustness and protein stability in highly polymorphic populations. We suggest that this phenomenon may contribute to the mutational robustness and evolvability of viruses and bacteria that exist in large populations.
2009-04-16
0704.1908
Radek Erban
Radek Erban, Jonathan Chapman and Philip Maini
A practical guide to stochastic simulations of reaction-diffusion processes
35 pages
null
null
null
q-bio.SC physics.ed-ph q-bio.QM
null
A practical introduction to stochastic modelling of reaction-diffusion processes is presented. No prior knowledge of stochastic simulations is assumed. The methods are explained using illustrative examples. The article starts with the classical Gillespie algorithm for the stochastic modelling of chemical reactions. Then stochastic algorithms for modelling molecular diffusion are given. Finally, basic stochastic reaction-diffusion methods are presented. The connections between stochastic simulations and deterministic models are explained and basic mathematical tools (e.g. chemical master equation) are presented. The article concludes with an overview of more advanced methods and problems.
2007-11-19
0704.1912
Adrian Melott
L.C. Natarajan, A.L. Melott, B.M. Rothschild, and L.D. Martin (University of Kansas)
Bone Cancer Rates in Dinosaurs Compared with Modern Vertebrates
As published in Transactions of the Kansas Academy of Science
TKAS 110, 155-158 (2007)
null
null
q-bio.PE astro-ph physics.geo-ph
null
Data on the prevalence of bone cancer in dinosaurs is available from past radiological examination of preserved bones. We statistically test this data for consistency with rates extrapolated from information on bone cancer in modern vertebrates, and find that there is no evidence of a different rate. Thus, this test provides no support for a possible role of ionizing radiation in the K-T extinction event.
2007-10-16
0704.2114
A. Mary Selvam
A. M. Selvam
Universal spectrum for DNA base CG frequency distribution in Takifugu rubripes (Puffer fish) genome
32 pages, 8 figures
null
null
null
physics.gen-ph physics.bio-ph
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
The frequency distribution of DNA bases A, C, G, T exhibit fractal fluctuations ubiquitous to dynamical systems in nature. The power spectra of fractal fluctuations exhibit inverse power law form signifying long-range correlations between local (small-scale) and global (large-scale) perturbations. The author has developed a general systems theory based on classical statistical physics for fractal fluctuations which predicts that the probability distribution of eddy amplitudes and the variance (square of eddy amplitude)spectrum of fractal fluctuations follow the universal Boltzmann inverse power law expressed as a function of the golden mean. The model predicted distribution is very close to statistical normal distribution for fluctuations within two standard deviations from the mean and exhibits a fat long tail. In this paper it is shown that DNA base CG frequency distribution in Takifugu rubripes (Puffer fish) Genome Release 4 exhibit universal inverse power law form consistent with model prediction. The observed long-range correlations in the DNA bases implies that the non-coding 'junk' or 'selfish' DNA which appear to be redundant, may also contribute to the efficient functioning of the protein coding DNA, a result supported by recent studies.
2011-03-07
0704.2132
Roberto Chignola
C. Tomelleri, E. Milotti, C. Dalla Pellegrina, O. Perbellini, A. Del Fabbro, M. T. Scupoli and R. Chignola
A quantitative study on the growth variability of tumour cell clones in vitro
31 pages, 5 figures
null
null
null
q-bio.CB q-bio.QM
null
Objectives: In this study, we quantify the growth variability of tumour cell clones from a human leukemia cell line. Materials and methods: We have used microplate spectrophotometry to measure the growth kinetics of hundreds of individual cell clones from the Molt3 cell line. The growth rate of each clonal population has been estimated by fitting experimental data with the logistic equation. Results: The growth rates were observed to vary among different clones. Up to six clones with a growth rate above or below the mean growth rate of the parent population were further cloned and the growth rates of their offsprings were measured. The distribution of the growth rates of the subclones did not significantly differ from that of the parent population thus suggesting that growth variability has an epigenetic origin. To explain the observed distributions of clonal growth rates we have developed a probabilistic model assuming that the fluctuations in the number of mitochondria through successive cell cycles are the leading cause of growth variability. For fitting purposes, we have estimated experimentally by flow cytometry the maximum average number of mitochondria in Molt3 cells. The model fits nicely the observed distributions of growth rates, however, cells in which the mitochondria were rendered non functional (rho-0 cells) showed only a 30% reduction in the clonal growth variability with respect to normal cells. Conclusions: A tumor cell population is a dynamic ensemble of clones with highly variable growth rate. At least part of this variability is due to fluctuations in the number of mitochondria.
2007-05-23
0704.2191
Bo Deng
Bo Deng
Mismatch Repair Error Implies Chargaff's Second Parity Rule
null
null
null
null
q-bio.GN
null
Chargaff's second parity rule holds empirically for most types of DNA that along single strands of DNA the base contents are equal for complimentary bases, A = T, G = C. A Markov chain model is constructed to track the evolution of any single base position along single strands of genomes whose organisms are equipped with replication mismatch repair. Under the key assumptions that mismatch error rates primarily depend the number of hydrogen bonds of nucleotides and that the mismatch repairing process itself makes strand recognition error, the model shows that the steady state probabilities for any base position to take on one of the 4 nucleotide bases are equal for complimentary bases. As a result, Chargaff's second parity rule is the manifestation of the Law of Large Number acting on the steady state probabilities. More importantly, because the model pinpoints mismatch repair as a basis of the rule, it is suitable for experimental verification.
2007-09-20
0704.2200
Stefan Bornholdt
Maria I. Davidich, Stefan Bornholdt
Boolean network model predicts cell cycle sequence of fission yeast
10 pages, 3 figures
null
10.1371/journal.pone.0001672
null
q-bio.MN
null
A Boolean network model of the cell-cycle regulatory network of fission yeast (Schizosaccharomyces Pombe) is constructed solely on the basis of the known biochemical interaction topology. Simulating the model in the computer, faithfully reproduces the known sequence of regulatory activity patterns along the cell cycle of the living cell. Contrary to existing differential equation models, no parameters enter the model except the structure of the regulatory circuitry. The dynamical properties of the model indicate that the biological dynamical sequence is robustly implemented in the regulatory network, with the biological stationary state G1 corresponding to the dominant attractor in state space, and with the biological regulatory sequence being a strongly attractive trajectory. Comparing the fission yeast cell-cycle model to a similar model of the corresponding network in S. cerevisiae, a remarkable difference in circuitry, as well as dynamics is observed. While the latter operates in a strongly damped mode, driven by external excitation, the S. pombe network represents an auto-excited system with external damping.
2015-05-13
0704.2260
Frederick Matsen IV
Frederick A. Matsen and Mike Steel
Phylogenetic mixtures on a single tree can mimic a tree of another topology
null
null
null
null
q-bio.PE
null
Phylogenetic mixtures model the inhomogeneous molecular evolution commonly observed in data. The performance of phylogenetic reconstruction methods where the underlying data is generated by a mixture model has stimulated considerable recent debate. Much of the controversy stems from simulations of mixture model data on a given tree topology for which reconstruction algorithms output a tree of a different topology; these findings were held up to show the shortcomings of particular tree reconstruction methods. In so doing, the underlying assumption was that mixture model data on one topology can be distinguished from data evolved on an unmixed tree of another topology given enough data and the ``correct'' method. Here we show that this assumption can be false. For biologists our results imply that, for example, the combined data from two genes whose phylogenetic trees differ only in terms of branch lengths can perfectly fit a tree of a different topology.
2007-06-30
0704.2346
Marcio Rocha
M. S. Rocha, M. C. Ferreira, and O. N. Mesquita
Transition on the entropic elasticity of DNA induced by intercalating molecules
This experimental article shows and discuss a transition observed in the persistence length of DNA molecules when studied as a function of some intercalating drug concentrations, like daunomycin and ethidium bromide. It has 15 pages and 4 figures. The article presented here is in preprint format
null
10.1063/1.2768945
null
physics.bio-ph physics.chem-ph
null
We use optical tweezers to perform stretching experiments on DNA molecules when interacting with the drugs daunomycin and ethidium bromide, which intercalate the DNA molecule. These experiments are performed in the low-force regime from zero up to 2 pN. Our results show that the persistence length of the DNA-drug complexes increases strongly as the drug concentration increases up to some critical value. Above this critical value, the persistence length decreases abruptly and remains practically constant for larger drug concentrations. The contour length of the molecules increases monotonically and saturates as drugs concentration increases. Measured in- tercalants critical concentrations for the persistence length transition coincide with reported values for the helix-coil transition of DNA-drug complexes, obtained from sedimentation experiments.
2009-11-13
0704.2409
Jose Vilar
Leonor Saiz and Jose M.G. Vilar
Multilevel Deconstruction of the In Vivo Behavior of Looped DNA-Protein Complexes
Open Access article available at http://www.plosone.org/article/fetchArticle.action?articleURI=info%3Adoi%2F10.1371%2Fjournal.pone.0000355
PLoS ONE 2(4): e355 (2007)
10.1371/journal.pone.0000355
null
q-bio.BM q-bio.SC
null
Protein-DNA complexes with loops play a fundamental role in a wide variety of cellular processes, ranging from the regulation of DNA transcription to telomere maintenance. As ubiquitous as they are, their precise in vivo properties and their integration into the cellular function still remain largely unexplored. Here, we present a multilevel approach that efficiently connects in both directions molecular properties with cell physiology and use it to characterize the molecular properties of the looped DNA-lac repressor complex while functioning in vivo. The properties we uncover include the presence of two representative conformations of the complex, the stabilization of one conformation by DNA architectural proteins, and precise values of the underlying twisting elastic constants and bending free energies. Incorporation of all this molecular information into gene-regulation models reveals an unprecedented versatility of looped DNA-protein complexes at shaping the properties of gene expression.
2007-05-23
0704.2454
Vahid Rezania
Vahid Rezania, Jack Tuszynski, Michael Hendzel
Modeling transcription factor binding events to DNA using a random walker/jumper representation on a 1D/2D lattice with different affinity sites
24 pages, 9 figures
Physical Biology, 4, 256-267 (2007)
10.1088/1478-3975/4/4/003
null
q-bio.QM q-bio.BM
null
Surviving in a diverse environment requires corresponding organism responses. At the cellular level, such adjustment relies on the transcription factors (TFs) which must rapidly find their target sequences amidst a vast amount of non-relevant sequences on DNA molecules. Whether these transcription factors locate their target sites through a 1D or 3D pathway is still a matter of speculation. It has been suggested that the optimum search time is when the protein equally shares its search time between 1D and 3D diffusions. In this paper, we study the above problem using a Monte Carlo simulation by considering a very simple physical model. A 1D strip, representing a DNA, with a number of low affinity sites, corresponding to non-target sites, and high affinity sites, corresponding to target sites, is considered and later extended to a 2D strip. We study the 1D and 3D exploration pathways, and combinations of the two modes by considering three different types of molecules: a walker that randomly walks along the strip with no dissociation; a jumper that represents dissociation and then re-association of a TF with the strip at later time at a distant site; and a hopper that is similar to the jumper but it dissociates and then re-associates at a faster rate than the jumper. We analyze the final probability distribution of molecules for each case and find that TFs can locate their targets fast enough even if they spend 15% of their search time diffusing freely in the solution. This indeed agrees with recent experimental results obtained by Elf et al. 2007 and is in contrast with theoretical expectation.
2009-11-13
0704.2474
Yi Xiao
Changjun Chen and Yi Xiao
Observation of Multiple folding Pathways of beta-hairpin Trpzip2 from Independent Continuous Folding Trajectories
13 pages, 8 figures
null
null
null
q-bio.BM
null
We report 10 successfully folding events of trpzip2 by molecular dynamics simulation. It is found that the trizip2 can fold into its native state through different zipper pathways, depending on the ways of forming hydrophobic core. We also find a very fast non-zipper pathway. This indicates that there may be no inconsistencies in the current pictures of beta-hairpin folding mechanisms. These pathways occur with different probabilities. zip-out is the most probable one. This may explain the recent experiment that the turn formation is the rate-limiting step for beta-hairpin folding.
2007-05-23
0704.2533
Frank Schweitzer
Frank Schweitzer
Multi-Agent Approach to the Self-Organization of Networks
20 papges, to appear in: F. Reed-Tsochas, N. F. Johnson, J. Efstathiou: Understanding and Managing Complex Agent-Based Dynamical Networks, Singapore: World Scientific (2007)
null
null
null
nlin.AO physics.bio-ph q-bio.QM
null
Is it possible to link a set of nodes without using preexisting positional information or any kind of long-range attraction of the nodes? Can the process of generating positional information, i.e. the detection of ``unknown'' nodes and the estabishment of chemical gradients, \emph{and} the process of network formation, i.e. the establishment of links between nodes, occur in parallel, on a comparable time scale, as a process of co-evolution? The paper discusses a model where the generation of relevant information for establishing the links between nodes results from the interaction of many \emph{agents}, i.e. subunits of the system that are capable of performing some activities. Their collective interaction is based on (indirect) communication, which also includes memory effects and the dissemination of information in the system. The relevant (``pragmatic'') information that leads to the establishment of the links then emerges from an evolutionary interplay of selection and reamplification.
2007-05-23
0704.2547
Remi Monasson
Valentina Baldazzi (LPS), Serena Bradde (LPS), Simona Cocco (LPS), Enzo Marinari, Remi Monasson (LPTENS)
Inferring DNA sequences from mechanical unzipping data: the large-bandwidth case
null
Phys. Rev. E 75 (2007) 011904
10.1103/PhysRevE.75.011904
null
q-bio.BM cond-mat.stat-mech
null
The complementary strands of DNA molecules can be separated when stretched apart by a force; the unzipping signal is correlated to the base content of the sequence but is affected by thermal and instrumental noise. We consider here the ideal case where opening events are known to a very good time resolution (very large bandwidth), and study how the sequence can be reconstructed from the unzipping data. Our approach relies on the use of statistical Bayesian inference and of Viterbi decoding algorithm. Performances are studied numerically on Monte Carlo generated data, and analytically. We show how multiple unzippings of the same molecule may be exploited to improve the quality of the prediction, and calculate analytically the number of required unzippings as a function of the bandwidth, the sequence content, the elasticity parameters of the unzipped strands.
2015-05-13
0704.2551
Sophie Lebre
Sophie L\`ebre (SG)
Inferring dynamic genetic networks with low order independencies
null
null
null
null
math.ST q-bio.QM stat.TH
http://arxiv.org/licenses/nonexclusive-distrib/1.0/
In this paper, we propose a novel inference method for dynamic genetic networks which makes it possible to face with a number of time measurements n much smaller than the number of genes p. The approach is based on the concept of low order conditional dependence graph that we extend here in the case of Dynamic Bayesian Networks. Most of our results are based on the theory of graphical models associated with the Directed Acyclic Graphs (DAGs). In this way, we define a minimal DAG G which describes exactly the full order conditional dependencies given the past of the process. Then, to face with the large p and small n estimation case, we propose to approximate DAG G by considering low order conditional independencies. We introduce partial qth order conditional dependence DAGs G(q) and analyze their probabilistic properties. In general, DAGs G(q) differ from DAG G but still reflect relevant dependence facts for sparse networks such as genetic networks. By using this approximation, we set out a non-bayesian inference method and demonstrate the effectiveness of this approach on both simulated and real data analysis. The inference procedure is implemented in the R package 'G1DBN' freely available from the CRAN archive.
2009-05-29
0704.2554
Yannick Brohard
Brigitte Meyer-Berthaud (AMAP), Anne-Laure Decombeix (AMAP)
A tree without leaves
null
Nature 446, 7138 (2006) 861-862
10.1038/446861a
A-07-09
q-bio.PE
null
The puzzle presented by the famous stumps of Gilboa, New York, finds a solution in the discovery of two fossil specimens that allow the entire structure of these early trees to be reconstructed.
2007-05-23
0704.2649
Mike Steel Prof.
Mike Steel, Aki Mimoto, Arne O. Mooers
Hedging our bets: the expected contribution of species to future phylogenetic diversity
19 pages, 2 figures
null
null
null
q-bio.PE
null
If predictions for species extinctions hold, then the `tree of life' today may be quite different to that in (say) 100 years. We describe a technique to quantify how much each species is likely to contribute to future biodiversity, as measured by its expected contribution to phylogenetic diversity. Our approach considers all possible scenarios for the set of species that will be extant at some future time, and weights them according to their likelihood under an independent (but not identical) distribution on species extinctions. Although the number of extinction scenarios can typically be very large, we show that there is a simple algorithm that will quickly compute this index. The method is implemented and applied to the prosimian primates as a test case, and the associated species ranking is compared to a related measure (the `Shapley index'). We describe indices for rooted and unrooted trees, and a modification that also includes the focal taxon's probability of extinction, making it directly comparable to some new conservation metrics.
2007-05-23
0704.2700
Ivan Degtyarenko Mr.
Ivan Degtyarenko, Karl J. Jalkanen, Andrey A. Gurtovenko and Risto M. Nieminen
The aqueous and crystalline forms of L-alanine zwitterion
preprint of 22 pages, 7 figures, and 2 tables
null
null
null
physics.bio-ph physics.chem-ph physics.comp-ph
null
The structural properties of L-alanine amino acid in aqueous solution and in crystalline phase have been studied by means of density-functional electronic-structure and molecular dynamics simulations. The solvated zwitterionic structure of L-alanine (+NH3-C2H4-COO-) was systematically compared to the structure of its zwitterionic crystalline analogue acquired from both computer simulations and experiments. It turns out that the structural properties of an alanine molecule in aqueous solution can differ significantly from those in crystalline phase, these differences being mainly attributed to hydrogen bonding interactions. In particular, we found that the largest difference between the two alanine forms can be seen for the orientation and bond lengths of the carboxylate (COO-) group: in aqueous solution the C-O bond lengths appear to strongly correlate with the number of water molecules which form hydrogen bonds with the COO- group. Furthermore, the hydrogen bond lengths are shorter and the hydrogen bond angles are larger for L-alanine in water as compared to crystal. Overall, our findings strongly suggest that the generally accepted approach of extending the structural information acquired from crystallographic data to a L-alanine molecule in aqueous solution should be used with caution.
2007-05-23
0704.2750
Nikolai Lebovka I
Nikolai Lebovka, Eugene Vorobiev
The kinetics of inactivation of spheroidal microbial cells by pulsed electric fields
12 pages, 10 figures
null
null
null
physics.bio-ph
null
The nature of non-exponential kinetics in microbial cells inactivation by pulsed electric fields (PEF) is discussed. It was demonstrated that possible mechanism of non-exponential kinetics can be related to orientational disorder in suspension of microbial cells of anisotropic form. A numerical studies of spheroidal cell suspensions was carried out. The most pronounced deviations from the exponential kinetics were observed for disordered suspensions of prolate spheroids at small electric field strength $E$ or at large aspect ratio $a$. For partially oriented suspensions, efficiency of inactivation enhances with increasing of order parameter and field strength. A possibility of the PEF-induced orientational ordering in microbial suspensions is discussed.
2007-05-23
0704.2793
Matthew Scott
Matthew Scott, Terence Hwa and Brian Ingalls
Deterministic characterization of stochastic genetic circuits
6 pages (Supplementary Information is appended)
Proceedings of the National Academy of Sciences USA (2007), vol. 104(18): 7402-7407
10.1073/pnas.0610468104
null
q-bio.MN q-bio.QM
null
For cellular biochemical reaction systems where the numbers of molecules is small, significant noise is associated with chemical reaction events. This molecular noise can give rise to behavior that is very different from the predictions of deterministic rate equation models. Unfortunately, there are few analytic methods for examining the qualitative behavior of stochastic systems. Here we describe such a method that extends deterministic analysis to include leading-order corrections due to the molecular noise. The method allows the steady-state behavior of the stochastic model to be easily computed, facilitates the mapping of stability phase diagrams that include stochastic effects and reveals how model parameters affect noise susceptibility, in a manner not accessible to numerical simulation. By way of illustration we consider two genetic circuits: a bistable positive-feedback loop and a negative-feedback oscillator. We find in the positive feedback circuit that translational activation leads to a far more stable system than transcriptional control. Conversely, in a negative-feedback loop triggered by a positive-feedback switch, the stochasticity of transcriptional control is harnessed to generate reproducible oscillations.
2009-11-13
0704.2794
Rafael Quintero-Torres
R. Quintero-Torres and J.L. Aragon, M. Torres, M. Estrada and L. Cros
Strong far field coherent scattering of ultraviolet radiation by holococcolithophores
4 pages and 4 figures
Phys Rev E Stat Nonlin Soft Matter Phys. 2006 Sep;74:2006 Sep 12
null
null
physics.bio-ph
null
By considering the structure of holococcoliths (calcite plates that cover holococcolithophores, a haploid phase of the coccolithophore life cycle) as a photonic structure, we apply a discrete dipolar approximation to study the light backscattering properties of these algae. We show that some holococcolith structures have the ability to scatter the ultraviolet (UV) radiation. This property may represent an advantage for holococcolithophores possessing it, by allowing them to live higher in the water column than other coccolithophores.
2007-05-23
0704.2896
Adrian Melott
Bruce S.Lieberman and Adrian L. Melott (University of Kansas)
Considering the Case for Biodiversity Cycles: Reexamining the Evidence for Periodicity in the Fossil Record
Minor modifications to reflect final published version
PLoS ONE 2(8): e759 (2007)
10.1371/journal.pone.0000759
null
q-bio.PE astro-ph physics.geo-ph
null
Medvedev and Melott (2007) have suggested that periodicity in fossil biodiversity may be induced by cosmic rays which vary as the Solar System oscillates normal to the galactic disk. We re-examine the evidence for a 62 million year (Myr) periodicity in biodiversity throughout the Phanerozoic history of animal life reported by Rohde & Mueller (2005), as well as related questions of periodicity in origination and extinction. We find that the signal is robust against variations in methods of analysis, and is based on fluctuations in the Paleozoic and a substantial part of the Mesozoic. Examination of origination and extinction is somewhat ambiguous, with results depending upon procedure. Origination and extinction intensity as defined by RM may be affected by an artifact at 27 Myr in the duration of stratigraphic intervals. Nevertheless, when a procedure free of this artifact is implemented, the 27 Myr periodicity appears in origination, suggesting that the artifact may ultimately be based on a signal in the data. A 62 Myr feature appears in extinction, when this same procedure is used. We conclude that evidence for a periodicity at 62 Myr is robust, and evidence for periodicity at approximately 27 Myr is also present, albeit more ambiguous.
2007-08-22
0704.2964
Ashok Palaniappan
Ashok Palaniappan
Fourier Analysis of Biological Evolution: Concept of Selection Moment
null
null
null
null
q-bio.BM q-bio.QM
null
Secondary structure elements of many protein families exhibit differential conservation on their opposing faces. Amphipathic helices and beta-sheets by definition possess this property, and play crucial functional roles. This type of evolutionary trajectory of a protein family is usually critical to the functions of the protein family, as well as in creating functions within subfamilies. That is, differential conservation maintains properties of a protein structure related to its orientation, and that are important in packing, recognition, and catalysis. Here I define and formulate a new concept, called the selection moment, that detects this evolutionary process in protein sequences. A treatment of its various applications is detailed.
2007-05-23
0704.3005
Yasser Roudi
Yasser Roudi, Peter E. Latham
A balanced memory network
Accepted for publications in PLoS Comp. Biol
null
10.1371/journal.pcbi.0030141
null
q-bio.NC cond-mat.dis-nn
null
A fundamental problem in neuroscience is understanding how working memory -- the ability to store information at intermediate timescales, like 10s of seconds -- is implemented in realistic neuronal networks. The most likely candidate mechanism is the attractor network, and a great deal of effort has gone toward investigating it theoretically. Yet, despite almost a quarter century of intense work, attractor networks are not fully understood. In particular, there are still two unanswered questions. First, how is it that attractor networks exhibit irregular firing, as is observed experimentally during working memory tasks? And second, how many memories can be stored under biologically realistic conditions? Here we answer both questions by studying an attractor neural network in which inhibition and excitation balance each other. Using mean field analysis, we derive a three-variable description of attractor networks. From this description it follows that irregular firing can exist only if the number of neurons involved in a memory is large. The same mean field analysis also shows that the number of memories that can be stored in a network scales with the number of excitatory connections, a result that has been suggested for simple models but never shown for realistic ones. Both of these predictions are verified using simulations with large networks of spiking neurons.
2015-05-13
0704.3049
Ryan Gutenkunst
Ryan N. Gutenkunst, Fergal P. Casey, Joshua J. Waterfall, Christopher R. Myers, James P. Sethna
Extracting falsifiable predictions from sloppy models
4 pages, 2 figures. Submitted to the Annals of the New York Academy of Sciences for publication in "Reverse Engineering Biological Networks: Opportunities and Challenges in Computational Methods for Pathway Inference"
Annals of the New York Academy of Sciences 1115:203-211 (2007)
10.1196/annals.1407.003
null
q-bio.QM
null
Successful predictions are among the most compelling validations of any model. Extracting falsifiable predictions from nonlinear multiparameter models is complicated by the fact that such models are commonly sloppy, possessing sensitivities to different parameter combinations that range over many decades. Here we discuss how sloppiness affects the sorts of data that best constrain model predictions, makes linear uncertainty approximations dangerous, and introduces computational difficulties in Monte-Carlo uncertainty analysis. We also present a useful test problem and suggest refinements to the standards by which models are communicated.
2007-11-24
0704.3071
Karina Mazzitello
K. I. Mazzitello, C. M. Arizmendi, and H. G. E. Hentschel
Converting genetic network oscillations into somite spatial pattern
7 pages, 7 figures
null
10.1103/PhysRevE.78.021906
null
q-bio.QM
null
In most vertebrate species, the body axis is generated by the formation of repeated transient structures called somites. This spatial periodicity in somitogenesis has been related to the temporally sustained oscillations in certain mRNAs and their associated gene products in the cells forming the presomatic mesoderm. The mechanism underlying these oscillations have been identified as due to the delays involved in the synthesis of mRNA and translation into protein molecules [J. Lewis, Current Biol. {\bf 13}, 1398 (2003)]. In addition, in the zebrafish embryo intercellular Notch signalling couples these oscillators and a longitudinal positional information signal in the form of an Fgf8 gradient exists that could be used to transform these coupled temporal oscillations into the observed spatial periodicity of somites. Here we consider a simple model based on this known biology and study its consequences for somitogenesis. Comparison is made with the known properties of somite formation in the zebrafish embryo . We also study the effects of localized Fgf8 perturbations on somite patterning.
2009-11-13
0704.3079
Ilia Solov'yov
Alexander V. Yakubovich, Ilia A. Solov'yov, Andrey V. Solov'yov and Walter Greiner
Ab initio theory of helix-coil phase transition
24 pages, 3 figures
null
10.1140/epjd/e2007-00328-9
null
physics.bio-ph physics.chem-ph
null
In this paper we suggest a theoretical method based on the statistical mechanics for treating the alpha-helix-random coil transition in alanine polypeptides. We consider this process as a first-order phase transition and develop a theory which is free of model parameters and is based solely on fundamental physical principles. It describes essential thermodynamical properties of the system such as heat capacity, the phase transition temperature and others from the analysis of the polypeptide potential energy surface calculated as a function of two dihedral angles, responsible for the polypeptide twisting. The suggested theory is general and with some modification can be applied for the description of phase transitions in other complex molecular systems (e.g. proteins, DNA, nanotubes, atomic clusters, fullerenes).
2009-11-13
0704.3085
Ilia Solov'yov
Ilia A. Solov'yov, Alexander V. Yakubovich, Andrey V. Solov'yov and Walter Greiner
Alpha helix-coil phase transition: analysis of ab initio theory predictions
34 pages, 12 figures
null
10.1140/epjd/e2007-00327-x
null
physics.bio-ph physics.chem-ph
null
In the present paper we present results of calculations obtained with the use of the theoretical method described in our preceding paper [1] and perform detail analysis of alpha helix-random coil transition in alanine polypeptides of different length. We have calculated the potential energy surfaces of polypeptides with respect to their twisting degrees of freedom and construct a parameter-free partition function of the polypeptide using the suggested method [1]. From the build up partition function we derive various thermodynamical characteristics for alanine polypeptides of different length as a function of temperature. Thus, we analyze the temperature dependence of the heat capacity, latent heat and helicity for alanine polypeptides consisting of 21, 30, 40, 50 and 100 amino acids. Alternatively, we have obtained same thermodynamical characteristics from the use of molecular dynamics simulations and compared them with the results of the new statistical mechanics approach. The comparison proves the validity of the statistical mechanic approach and establishes its accuracy.
2009-11-13
0704.3138
Branislav Brutovsky
Branislav Brutovsky, Denis Horvath and Vladimir Lisy
Inverse Geometric Approach to the Simulation of the Circular Growth. The Case of Multicellular Tumor Spheroids
null
null
10.1016/j.physa.2007.10.036
null
q-bio.CB
null
We demonstrate the power of the genetic algorithms to construct the cellular automata model simulating the growth of 2-dimensional close-to-circular clusters revealing the desired properties, such as the growth rate and, at the same time, the fractal behavior of their contours. The possible application of the approach in the field of tumor modeling is outlined.
2009-11-13
0704.3172
Debaprasad Giri
Sanjay Kumar and Debaprasad Giri
Force induced conformational transition in a system of interacting stiff polymer: Application to unfolding
RevTeX v4, 9 pages with 6 eps figures
Phys. Rev. E 72, 052901 (2005)
10.1103/PhysRevE.72.052901
BHU-PHY/CMPT/05-01
cond-mat.soft cond-mat.stat-mech physics.bio-ph
null
We consider a stiff polymer chain in poor solvent and apply a force at one end of the chain. We find that by varying the stiffness parameter, polymer undergoes a transition from the globule state to the folded like state. The conformation of folded state mimics the $\beta$-sheet as seen in titin molecule. Using exact enumeration technique, we study the extension-force and force-temperature diagrams of such a system. Force-temperature diagram shows the re-entrance behaviour for flexible chain. However, for stiff chain this re-entrance behaviour is absent and there is an enhancement in $\theta$-temperature with the rise of stiffness. We further propose that the internal information about the frozen structure of polymer can be read from the distribution of end-to-end distance which shows saw-tooth like behaviour.
2015-05-13
0704.3174
Ma\'ira Aguiar
Ma\'ira Aguiar, Nico Stollenwerk
A new chaotic attractor in a basic multi-strain epidemiological model with temporary cross-immunity
16 pages, 15 figures
null
null
null
nlin.CD q-bio.PE
null
An epidemic multi-strain model with temporary cross-immunity shows chaos, even in a previously unexpected parameter region. Especially dengue fever models with strong enhanced infectivity on secondary infection have previously shown deterministic chaos motivated by experimental findings of antibody-dependent-enhancement (ADE). Including temporary cross-immunity in such models, which is common knowledge among field researchers in dengue, we find a deterministically chaotic attractor in the more realistic parameter region of reduced infectivity on secondary infection (''inverse ADE'' parameter region). This is realistic for dengue fever since on second infection people are more likely to be hospitalized, hence do not contribute to the force of infection as much as people with first infection. Our finding has wider implications beyond dengue in any multi-strain epidemiological systems with altered infectivity upon secondary infection, since we can relax the condition of rather high infectivity on secondary infection previously required for deterministic chaos. For dengue the finding of wide ranges of chaotic attractors open new ways to analysis of existing data sets.
2007-06-25
0704.3175
Debaprasad Giri
Debaprasad Giri and Sanjay Kumar
Effects of Eye-phase in DNA unzipping
RevTeX v4, 9 pages with 7 eps figures
Phys. Rev. E 73, 050903(R) (2006)
10.1103/PhysRevE.73.050903
BHU-PHY/CMPT/05-03
cond-mat.soft cond-mat.stat-mech physics.bio-ph
null
The onset of an "eye-phase" and its role during the DNA unzipping is studied when a force is applied to the interior of the chain. The directionality of the hydrogen bond introduced here shows oscillations in force-extension curve similar to a "saw-tooth" kind of oscillations seen in the protein unfolding experiments. The effects of intermediates (hairpins) and stacking energies on the melting profile have also been discussed.
2015-05-13
0704.3193
Elsa Henriques S
Elsa S. Henriques, Andrey V. Solov'yov
A Rational Method for Probing Macromolecules Dissociation: The Antibody-Hapten System
22 pages, 10 figures
null
10.1140/epjd/e2008-00009-3
null
physics.bio-ph physics.chem-ph
null
The unbinding process of a protein-ligand complex of major biological interest was investigated by means of a computational approach at atomistic classical mechanical level. An energy minimisation-based technique was used to determine the dissociation paths of the system by probing only a relevant set of generalized coordinates. The complex problem was reduced to a low-dimensional scanning along a selected distance between the protein and the ligand. Orientational coordinates of the escaping fragment (the ligand) were also assessed in order to further characterise the unbinding. Solvent effects were accounted for by means of the Poisson--Boltzmann continuum model. The corresponding dissociation time was derived from the calculated barrier height, in compliance with the experimentally reported Arrhenius-like behaviour. The computed results are in good agreement with the available experimental data.
2009-11-13
0704.3221
Manuel Lladser
Manuel Lladser, M. D. Betterton, Rob Knight
Multiple pattern matching: A Markov chain approach
Final version to appear in the Journal of Mathematical Biology
null
null
null
math.PR math.CO math.ST q-bio.GN q-bio.QM stat.TH
null
RNA motifs typically consist of short, modular patterns that include base pairs formed within and between modules. Estimating the abundance of these patterns is of fundamental importance for assessing the statistical significance of matches in genomewide searches, and for predicting whether a given function has evolved many times in different species or arose from a single common ancestor. In this manuscript, we review in an integrated and self-contained manner some basic concepts of automata theory, generating functions and transfer matrix methods that are relevant to pattern analysis in biological sequences. We formalize, in a general framework, the concept of Markov chain embedding to analyze patterns in random strings produced by a memoryless source. This conceptualization, together with the capability of automata to recognize complicated patterns, allows a systematic analysis of problems related to the occurrence and frequency of patterns in random strings. The applications we present focus on the concept of synchronization of automata, as well as automata used to search for a finite number of keywords (including sets of patterns generated according to base pairing rules) in a general text.
2007-05-23
0704.3223
Benedikt Obermayer
Benedikt Obermayer and Oskar Hallatschek
Coupling of transverse and longitudinal response in stiff polymers
4 pages, 3 figures, 1 table; final version
Phys. Rev. Lett. 99 (2007) 098302
10.1103/PhysRevLett.99.098302
LMU-ASC 25/07
cond-mat.soft q-bio.BM
null
The time-dependent transverse response of stiff polymers, represented as weakly-bending wormlike chains (WLCs), is well-understood on the linear level, where transverse degrees of freedom evolve independently from the longitudinal ones. We show that, beyond a characteristic time scale, the nonlinear coupling of transverse and longitudinal motion in an inextensible WLC significantly weakens the polymer response compared to the widely used linear response predictions. The corresponding feedback mechanism is rationalized by scaling arguments and quantified by a multiple scale approach that exploits an inherent separation of transverse and longitudinal correlation length scales. Crossover scaling laws and exact analytical and numerical solutions for characteristic response quantities are derived for different experimentally relevant setups. Our findings are applicable to cytoskeletal filaments as well as DNA under tension.
2007-09-03
0704.3226
Radhakrishnan Nagarajan
Radhakrishnan Nagarajan
Delay estimation in a two-node acyclic network
33 Pages, 6 Figures
Physica A: Volume 376, 15 March 2007, Pages 725-737
10.1016/j.physa.2006.10.067
null
q-bio.QM q-bio.MN
null
Linear measures such as cross-correlation have been used successfully to determine time delays from the given processes. Such an analysis often precedes identifying possible causal relationships between the observed processes. The present study investigates the impact of a positively correlated driver whose correlation function decreases monotonically with lag on the delay estimation in a two-node acyclic network with one and two-delays. It is shown that cross-correlation analysis of the given processes can result in spurious identification of multiple delays between the driver and the dependent processes. Subsequently, delay estimation of increment process as opposed to the original process under certain implicit constraints is explored. Short-range and long-range correlated driver processes along with those of their coarse-grained counterparts are considered.
2015-05-13
0704.3259
James P. Sethna
Christopher R. Myers, Ryan N. Gutenkunst, and James. P. Sethna
Python Unleashed on Systems Biology
Submitted to special issue of CiSE
null
null
null
q-bio.QM q-bio.MN
null
We have built an open-source software system for the modeling of biomolecular reaction networks, SloppyCell, which is written in Python and makes substantial use of third-party libraries for numerics, visualization, and parallel programming. We highlight here some of the powerful features that Python provides that enable SloppyCell to do dynamic code synthesis, symbolic manipulation, and parallel exploration of complex parameter spaces.
2007-05-23
0704.3263
Dominique Jean-Marie Mornet
Karim Hnia, G\'erald Hugon, Ahmed Masmoudi, Jacques Mercier, Fran\c{c}ois Rivier, Dominique Jean-Marie Mornet
Effect of beta-Dystroglycan Processing on Utrophin / DP116 Anchorage in Normal and MDX Mouse Schwann Cell Membrane
null
Neuroscience 141 (18/04/2006) 607-620
10.1016/J.neuroscience.2006.04.043
null
q-bio.NC
null
In the peripheral nervous system, utrophin and the short dystrophin isoform (Dp116) are co-localized at the outermost layer of the myelin sheath of nerve fibers; together with the dystroglycan complex. In peripheral nerve, matrix metalloproteinase (MMP) creates a 30 kDa fragment of beta-dystroglycan, leading to a disruption of the link between the extracellular matrix and the cell membrane. Here we asked if the processing of the beta-dystroglycan could influence the anchorage of Dp116 or/and utrophin in normal and mdx Schwann cell membrane. We showed that MMP-9 was more activated in mdx nerve than in wild-type one. This activation leads to an accumulation of the 30 kDa beta-dystroglycan isoform and have an impact on the anchorage of Dp116 and utrophin isoforms in mdx Schwann cells membrane. Our results showed that Dp116 had greater affinity to the full length form of beta-dystroglycan than the 30 kDa form. Moreover, we showed for the first time that the short isoform of utrophin (Up71) was over-expressed in mdx Schwann cells compared to wild-type. In addition, this utrophin isoform (Up71) seems to have greater affinity to the 30 kDa beta-dystroglycan which could explain a more stabilization of this 30 kDa at the membrane compartment. Our results highlight the potential participation of the short utrophin isoform and the cleaved form of beta-dystroglycan in mdx Schwann cell membrane architecture.
2007-05-23
0704.3264
Jose Vilar
Leonor Saiz and Jose M. G. Vilar
Efficiency and versatility of distal multisite transcription regulation
null
null
null
null
q-bio.SC q-bio.MN
null
Transcription regulation typically involves the binding of proteins over long distances on multiple DNA sites that are brought close to each other by the formation of DNA loops. The inherent complexity of the assembly of regulatory complexes on looped DNA challenges the understanding of even the simplest genetic systems, including the prototypical lac operon. Here we implement a scalable quantitative computational approach to analyze systems regulated through multiple DNA sites with looping. Our approach applied to the lac operon accurately predicts the transcription rate over five orders of magnitude for wild type and seven mutants accounting for all the combinations of deletions of the three operators. A quantitative analysis of the model reveals that the presence of three operators provides a mechanism to combine robust repression with sensitive induction, two seemingly mutually exclusive properties that are required for optimal functioning of metabolic switches.
2007-05-23
0704.3312
Yohan Payan
Nicolas Vuillerme (TIMC - IMAG), Olivier Chenu (TIMC - IMAG), Alexandre Moreau-Gaudry (TIMC - IMAG), Jacques Demongeot (TIMC - IMAG), Yohan Payan (TIMC - IMAG)
Artificial Tongue-Placed Tactile Biofeedback for perceptual supplementation: application to human disability and biomedical engineering
null
Human Machine iNteraction Conference Human'07 (2007) 105-112
null
null
physics.med-ph q-bio.NC
null
The present paper aims at introducing the innovative technologies, based on the concept of "sensory substitution" or "perceptual supplementation", we are developing in the fields of human disability and biomedical engineering. Precisely, our goal is to design, develop and validate practical assistive biomedical and/technical devices and/or rehabilitating procedures for persons with disabilities, using artificial tongue-placed tactile biofeedback systems. Proposed applications are dealing with: (1) pressure sores prevention in case of spinal cord injuries (persons with paraplegia, or tetraplegia); (2) ankle proprioceptive acuity improvement for driving assistance in older and/or disabled adults; and (3) balance control improvement to prevent fall in older and/or disabled adults. This paper presents results of three feasibility studies performed on young healthy adults.
2007-05-23
0704.3321
Chikara Furusawa
Chikara Furusawa and Kunihiko Kaneko
A generic mechanism for adaptive growth rate regulation
14 pages, 5 figures, submitted to PLoS Computational Biology
null
10.1371/journal.pcbi.0040003
null
q-bio.MN
null
How can a microorganism adapt to a variety of environmental conditions despite there exists a limited number of signal transduction machineries? We show that for any growing cells whose gene expression is under stochastic fluctuations, adaptive cellular state is inevitably selected by noise, even without specific signal transduction network for it. In general, changes in protein concentration in a cell are given by its synthesis minus dilution and degradation, both of which are proportional to the rate of cell growth. In an adaptive state with a higher growth speed, both terms are large and balanced. Under the presence of noise in gene expression, the adaptive state is less affected by stochasticity since both the synthesis and dilution terms are large, while for a non-adaptive state both the terms are smaller so that cells are easily kicked out of the original state by noise. Hence, escape time from a cellular state and the cellular growth rate are negatively correlated. This leads to a selection of adaptive states with higher growth rates, and model simulations confirm this selection to take place in general. The results suggest a general form of adaptation that has never been brought to light - a process that requires no specific machineries for sensory adaptation. The present scheme may help explain a wide range of cellular adaptive responses including the metabolic flux optimization for maximal cell growth.
2015-05-13
0704.3356
Yohan Payan
Alexandre Moreau-Gaudry (TIMC - IMAG), Anne Prince (CMUDD), Jacques Demongeot (TIMC - IMAG), Yohan Payan (TIMC - IMAG)
Pr\'evention des escarres chez les parapl\'egiques : une nouvelle approche par \'electrostimulation linguale
null
Actes de la 4\`eme Conf\'erence Handicap 2006 "Nouvelles Technologies au service de l'homme" (2006) 216-220
null
null
physics.med-ph q-bio.NC
null
Pressure ulcers are recognized as a major health issue in individuals with spinal cord injuries and new approaches to prevent this pathology are necessary. An innovative health strategy is being developed through the use of computer and sensory substitution via the tongue in order to compensate for the sensory loss in the buttock area for individuals with paraplegia. This sensory compensation will enable individuals with spinal cord injuries to be aware of a localized excess of pressure at the skin/seat interface and, consequently, will enable them to prevent the formation of pressure ulcers by relieving the cutaneous area of suffering. This work reports an initial evaluation of this approach and the feasibility of creating an adapted behavior, with a change in pressure as a response to electro-stimulated information on the tongue. Obtained during a clinical study in 10 healthy seated subjects, the first results are encouraging, with 92% success in 100 performed tests. These results, which have to be completed and validated in the paraplegic population, may lead to a new approach to education in health to prevent the formation of pressure ulcers within this population. Keywords: Spinal Cord Injuries, Pressure Ulcer, Sensory Substitution, Health Education, Biomedical Informatics.
2007-05-23
0704.3365
Takehiro Nagasima
Takehiro Nagasima, Akira R. Kinjo, Takashi Mitsui, Ken Nishikawa
Wang-Landau molecular dynamics technique to search for low-energy conformational space of proteins
8 pages, 7 figures, accepted for publication in Physical Review E
Phys. Rev. E 75, 066706 (2007)
10.1103/PhysRevE.75.066706
null
physics.comp-ph physics.bio-ph
null
Multicanonical molecular dynamics (MD) is a powerful technique for sampling conformations on rugged potential surfaces such as protein. However, it is notoriously difficult to estimate the multicanonical temperature effectively. Wang and Landau developed a convenient method for estimating the density of states based on a multicanonical Monte Carlo method. In their method, the density of states is calculated autonomously during a simulation. In this paper we develop a set of techniques to effectively apply the Wang-Landau method to MD simulations. In the multicanonical MD, the estimation of the derivative of the density of states is critical. In order to estimate it accurately, we devise two original improvements. First, the correction for the density of states is made smooth by using the Gaussian distribution obtained by a short canonical simulation. Second, an approximation is applied to the derivative, which is based on the Gaussian distribution and the multiple weighted histogram technique. A test of this method was performed with small polypeptides, Met-enkephalin and Trp-cage, and it is demonstrated that Wang-Landau MD is consistent with replica exchange MD but can sample much larger conformational space.
2007-11-01
0704.3406
Martin Weigt
Hamed Mahmoudi, Andrea Pagnani, Martin Weigt, Riccardo Zecchina
Propagation of external regulation and asynchronous dynamics in random Boolean networks
19 pages, 14 figures, to appear in Chaos
Chaos 17, 026109 (2007)
10.1063/1.2742931
null
cond-mat.stat-mech cond-mat.dis-nn q-bio.MN
null
Boolean Networks and their dynamics are of great interest as abstract modeling schemes in various disciplines, ranging from biology to computer science. Whereas parallel update schemes have been studied extensively in past years, the level of understanding of asynchronous updates schemes is still very poor. In this paper we study the propagation of external information given by regulatory input variables into a random Boolean network. We compute both analytically and numerically the time evolution and the asymptotic behavior of this propagation of external regulation (PER). In particular, this allows us to identify variables which are completely determined by this external information. All those variables in the network which are not directly fixed by PER form a core which contains in particular all non-trivial feedback loops. We design a message-passing approach allowing to characterize the statistical properties of these cores in dependence of the Boolean network and the external condition. At the end we establish a link between PER dynamics and the full random asynchronous dynamics of a Boolean network.
2007-07-19
0704.3453
Tshilidzi Marwala
S. Mohamed, D. Rubin, and T. Marwala
An Adaptive Strategy for the Classification of G-Protein Coupled Receptors
9 pages, 5 tables, 3 figures
null
null
null
cs.AI q-bio.QM
null
One of the major problems in computational biology is the inability of existing classification models to incorporate expanding and new domain knowledge. This problem of static classification models is addressed in this paper by the introduction of incremental learning for problems in bioinformatics. Many machine learning tools have been applied to this problem using static machine learning structures such as neural networks or support vector machines that are unable to accommodate new information into their existing models. We utilize the fuzzy ARTMAP as an alternate machine learning system that has the ability of incrementally learning new data as it becomes available. The fuzzy ARTMAP is found to be comparable to many of the widespread machine learning systems. The use of an evolutionary strategy in the selection and combination of individual classifiers into an ensemble system, coupled with the incremental learning ability of the fuzzy ARTMAP is proven to be suitable as a pattern classifier. The algorithm presented is tested using data from the G-Coupled Protein Receptors Database and shows good accuracy of 83%. The system presented is also generally applicable, and can be used in problems in genomics and proteomics.
2007-06-25
0704.3551
J\"org Langowski
Annika Wedemeier, Holger Merlitz, Chen-Xu Wu, and J\"org Langowski
Modelling diffusional transport in the interphase cell nucleus
9 pages, 8 figures
null
10.1063/1.2753158
null
physics.bio-ph physics.comp-ph
null
In this paper a lattice model for diffusional transport of particles in the interphase cell nucleus is proposed. Dense networks of chromatin fibers are created by three different methods: randomly distributed, non-interconnected obstacles, a random walk chain model, and a self avoiding random walk chain model with persistence length. By comparing a discrete and a continuous version of the random walk chain model, we demonstrate that lattice discretization does not alter particle diffusion. The influence of the 3D geometry of the fiber network on the particle diffusion is investigated in detail, while varying occupation volume, chain length, persistence length and walker size. It is shown that adjacency of the monomers, the excluded volume effect incorporated in the self avoiding random walk model, and, to a lesser extent, the persistence length, affect particle diffusion. It is demonstrated how the introduction of the effective chain occupancy, which is a convolution of the geometric chain volume with the walker size, eliminates the conformational effects of the network on the diffusion, i.e., when plotting the diffusion coefficient as a function of the effective chain volume, the data fall onto a master curve.
2009-11-13
0704.3560
Christian Blum
Christian Blum, Willem L. Vos, and Vinod Subramaniam
Tuning Spontaneous Emission versus Forster Energy Transfer in Biological Systems by Manipulating the Density of Photonic States
12 pages, 3 figures, pdf
null
null
null
physics.chem-ph physics.bio-ph
null
We theoretically discuss how to tune the competition between Forster transfer and spontaneous emission in a continuous and nondestructive fashion. The proposed approach is especially suitable for delicate biological systems like light harvesting complexes and fluorescent protein oligomers. We demonstrate that the manipulation of the density of photonic states at the emission frequency of the energy donor results in a change of the quantum efficiencies of the competing energy transfer and spontaneous emission processes. This change will be manifested in a modification of the donor and acceptor emission intensities. Thus, by controlling the local density of photonic states Forster coupled systems can be manipulated and analyzed without the need to physically separate donor and acceptor chromophores for individual analysis, which is of interest, for example, for oligomeric reef coral fluorescent proteins.
2007-06-19
0704.3619
Marcus Kaiser
Luciano da F Costa, Marcus Kaiser, Claus C Hilgetag
Predicting the connectivity of primate cortical networks from topological and spatial node properties
null
BMC Systems Biology 2007, 1:16
10.1186/1752-0509-1-16
null
q-bio.NC physics.soc-ph
null
The organization of the connectivity between mammalian cortical areas has become a major subject of study, because of its important role in scaffolding the macroscopic aspects of animal behavior and intelligence. In this study we present a computational reconstruction approach to the problem of network organization, by considering the topological and spatial features of each area in the primate cerebral cortex as subsidy for the reconstruction of the global cortical network connectivity. Starting with all areas being disconnected, pairs of areas with similar sets of features are linked together, in an attempt to recover the original network structure. Inferring primate cortical connectivity from the properties of the nodes, remarkably good reconstructions of the global network organization could be obtained, with the topological features allowing slightly superior accuracy to the spatial ones. Analogous reconstruction attempts for the C. elegans neuronal network resulted in substantially poorer recovery, indicating that cortical area interconnections are relatively stronger related to the considered topological and spatial properties than neuronal projections in the nematode. The close relationship between area-based features and global connectivity may hint on developmental rules and constraints for cortical networks. Particularly, differences between the predictions from topological and spatial properties, together with the poorer recovery resulting from spatial properties, indicate that the organization of cortical networks is not entirely determined by spatial constraints.
2007-05-23
0704.3639
Filipe Tostevin
Filipe Tostevin, Pieter Rein ten Wolde, Martin Howard
Fundamental Limits to Position Determination by Concentration Gradients
24 pages, 2 figures
PLoS Computational Biology 3 e78 (2007)
10.1371/journal.pcbi.0030078
null
q-bio.SC cond-mat.stat-mech
null
Position determination in biological systems is often achieved through protein concentration gradients. Measuring the local concentration of such a protein with a spatially-varying distribution allows the measurement of position within the system. In order for these systems to work effectively, position determination must be robust to noise. Here, we calculate fundamental limits to the precision of position determination by concentration gradients due to unavoidable biochemical noise perturbing the gradients. We focus on gradient proteins with first order reaction kinetics. Systems of this type have been experimentally characterised in both developmental and cell biology settings. For a single gradient we show that, through time-averaging, great precision can potentially be achieved even with very low protein copy numbers. As a second example, we investigate the ability of a system with oppositely directed gradients to find its centre. With this mechanism, positional precision close to the centre improves more slowly with increasing averaging time, and so longer averaging times or higher copy numbers are required for high precision. For both single and double gradients, we demonstrate the existence of optimal length scales for the gradients, where precision is maximized, as well as analyzing how precision depends on the size of the concentration measuring apparatus. Our results provide fundamental constraints on the positional precision supplied by concentration gradients in various contexts, including both in developmental biology and also within a single cell.
2007-05-23
0704.3640
Dennis Wylie
Dennis Cates Wylie
Linked by Loops: Network Structure and Switch Integration in Complex Dynamical Systems
21 pages, 5 figures. Paper simplified and shortened. Quantities presented in table 1 are different, though related, to quantities previously presented in table 1
null
null
null
q-bio.QM cond-mat.dis-nn math.DS nlin.CD
null
Simple nonlinear dynamical systems with multiple stable stationary states are often taken as models for switchlike biological systems. This paper considers the interaction of multiple such simple multistable systems when they are embedded together into a larger dynamical "supersystem." Attention is focused on the network structure of the resulting set of coupled differential equations, and the consequences of this structure on the propensity of the embedded switches to act independently versus cooperatively. Specifically, it is argued that both larger average and larger variance of the node degree distribution lead to increased switch independence. Given the frequency of empirical observations of high variance degree distributions (e.g., power-law) in biological networks, it is suggested that the results presented here may aid in identifying switch-integrating subnetworks as comparatively homogenous, low-degree, substructures. Potential applications to ecological problems such as the relationship of stability and complexity are also briefly discussed.
2008-04-10
0704.3715
Pablo Echenique
Pablo Echenique, J. L. Alonso
Efficient model chemistries for peptides. I. Split-valence Gaussian basis sets and the heterolevel approximation in RHF and MP2
54 pages, 16 figures, LaTeX, AMSTeX, Submitted to J. Comp. Chem
J. Comp. Chem. (2008) 1408-1422
10.1002/jcc.20900
null
q-bio.QM cond-mat.soft q-bio.BM
null
We present an exhaustive study of more than 250 ab initio potential energy surfaces (PESs) of the model dipeptide HCO-L-Ala-NH2. The model chemistries (MCs) used are constructed as homo- and heterolevels involving possibly different RHF and MP2 calculations for the geometry and the energy. The basis sets used belong to a sample of 39 selected representants from Pople's split-valence families, ranging from the small 3-21G to the large 6-311++G(2df,2pd). The reference PES to which the rest are compared is the MP2/6-311++G(2df,2pd) homolevel, which, as far as we are aware, is the more accurate PES of a dipeptide in the literature. The aim of the study presented is twofold: On the one hand, the evaluation of the influence of polarization and diffuse functions in the basis set, distinguishing between those placed at 1st-row atoms and those placed at hydrogens, as well as the effect of different contraction and valence splitting schemes. On the other hand, the investigation of the heterolevel assumption, which is defined here to be that which states that heterolevel MCs are more efficient than homolevel MCs. The heterolevel approximation is very commonly used in the literature, but it is seldom checked. As far as we know, the only tests for peptides or related systems, have been performed using a small number of conformers, and this is the first time that this potentially very economical approximation is tested in full PESs. In order to achieve these goals, all data sets have been compared and analyzed in a way which captures the nearness concept in the space of MCs.
2013-06-21
0704.3724
Paul Smolen
Paul Smolen
A Model of Late Long-Term Potentiation Simulates Aspects of Memory Maintenance
Accepted to PLoS One. 8 figures at end
null
10.1371/journal.pone.0000445
null
q-bio.NC q-bio.MN
null
Late long-term potentiation (L-LTP) appears essential for the formation of long-term memory, with memories at least partly encoded by patterns of strengthened synapses. How memories are preserved for months or years, despite molecular turnover, is not well understood. Ongoing recurrent neuronal activity, during memory recall or during sleep, has been hypothesized to preferentially potentiate strong synapses, preserving memories. This hypothesis has not been evaluated in the context of a mathematical model representing biochemical pathways important for L-LTP. I incorporated ongoing activity into two such models: a reduced model that represents some of the essential biochemical processes, and a more detailed published model. The reduced model represents synaptic tagging and gene induction intuitively, and the detailed model adds activation of essential kinases by Ca. Ongoing activity was modeled as continual brief elevations of [Ca]. In each model, two stable states of synaptic weight resulted. Positive feedback between synaptic weight and the amplitude of ongoing Ca transients underlies this bistability. A tetanic or theta-burst stimulus switches a model synapse from a low weight to a high weight stabilized by ongoing activity. Bistability was robust to parameter variations. Simulations illustrated that prolonged decreased activity reset synapses to low weights, suggesting a plausible forgetting mechanism. However, episodic activity with shorter inactive intervals maintained strong synapses. Both models support experimental predictions. Tests of these predictions are expected to further understanding of how neuronal activity is coupled to maintenance of synaptic strength.
2015-05-13
0704.3730
Volkan Sevim
Volkan Sevim, Per Arne Rikvold
Network Growth with Preferential Attachment for High Indegree and Low Outdegree
null
Physica A, Volume 387, Issue 11, 2631-2636 (2008)
10.1016/j.physa.2008.01.034
null
cond-mat.stat-mech q-bio.PE
null
We study the growth of a directed transportation network, such as a food web, in which links carry resources. We propose a growth process in which new nodes (or species) preferentially attach to existing nodes with high indegree (in food-web language, number of prey) and low outdegree (or number of predators). This scheme, which we call inverse preferential attachment, is intended to maximize the amount of resources available to each new node. We show that the outdegree (predator) distribution decays at least exponentially fast for large outdegree and is continuously tunable between an exponential distribution and a delta function. The indegree (prey) distribution is poissonian in the large-network limit.
2008-03-17
0704.3748
Gerald A. Miller
Gerald A. Miller, Yi Y. Shi, Hong Qian, and Karol Bomsztyk
Clustering Coefficients of Protein-Protein Interaction Networks
16 pages, 3 figures, in Press PRE uses pdflatex
Phys. Rev. E 75, 051910 (2007)
10.1103/PhysRevE.75.051910
null
q-bio.QM cond-mat.stat-mech physics.bio-ph q-bio.MN
null
The properties of certain networks are determined by hidden variables that are not explicitly measured. The conditional probability (propagator) that a vertex with a given value of the hidden variable is connected to k of other vertices determines all measurable properties. We study hidden variable models and find an averaging approximation that enables us to obtain a general analytical result for the propagator. Analytic results showing the validity of the approximation are obtained. We apply hidden variable models to protein-protein interaction networks (PINs) in which the hidden variable is the association free-energy, determined by distributions that depend on biochemistry and evolution. We compute degree distributions as well as clustering coefficients of several PINs of different species; good agreement with measured data is obtained. For the human interactome two different parameter sets give the same degree distributions, but the computed clustering coefficients differ by a factor of about two. This shows that degree distributions are not sufficient to determine the properties of PINs.
2009-11-13
0704.3771
James P. Crutchfield
Olof Gornerup and James P. Crutchfield
Primordial Evolution in the Finitary Process Soup
7 pages, 10 figures; http://cse.ucdavis.edu/~cmg/compmech/pubs/pefps.htm
null
10.1142/9789812779953_0012
null
q-bio.PE q-bio.MN
null
A general and basic model of primordial evolution--a soup of reacting finitary and discrete processes--is employed to identify and analyze fundamental mechanisms that generate and maintain complex structures in prebiotic systems. The processes--$\epsilon$-machines as defined in computational mechanics--and their interaction networks both provide well defined notions of structure. This enables us to quantitatively demonstrate hierarchical self-organization in the soup in terms of complexity. We found that replicating processes evolve the strategy of successively building higher levels of organization by autocatalysis. Moreover, this is facilitated by local components that have low structural complexity, but high generality. In effect, the finitary process soup spontaneously evolves a selection pressure that favors such components. In light of the finitary process soup's generality, these results suggest a fundamental law of hierarchical systems: global complexity requires local simplicity.
2016-11-23
0704.3808
Jakob Enemark
Jakob Enemark and Kim Sneppen
On Gene Duplication Models for Evolving Regulatory Networks
14 pages, 7 figures
null
10.1088/1742-5468/2007/11/P11007
null
q-bio.PE q-bio.OT
null
Background: Duplication of genes is important for evolution of molecular networks. Many authors have therefore considered gene duplication as a driving force in shaping the topology of molecular networks. In particular it has been noted that growth via duplication would act as an implicit way of preferential attachment, and thereby provide the observed broad degree distributions of molecular networks. Results: We extend current models of gene duplication and rewiring by including directions and the fact that molecular networks are not a result of unidirectional growth. We introduce upstream sites and downstream shapes to quantify potential links during duplication and rewiring. We find that this in itself generates the observed scaling of transcription factors for genome sites in procaryotes. The dynamical model can generate a scale-free degree distribution, p(k)∝ 1/k^γ, with exponent γ=1 in the non-growing case, and with γ>1 when the network is growing. Conclusions: We find that duplication of genes followed by substantial recombination of upstream regions could generate main features of genetic regulatory networks. Our steady state degree distribution is however to broad to be consistent with data, thereby suggesting that selective pruning acts as a main additional constraint on duplicated genes. Our analysis shows that gene duplication can only be a main cause for the observed broad degree distributions, if there is also substantial recombinations between upstream regions of genes.
2009-11-13
0704.3809
Laurent Cognet
David Lasne (CPMOH), Gerhard A. Blab (CPMOH), St\'ephane Berciaud (CPMOH), Martin Heine (PCS), Laurent Groc (PCS), Daniel Choquet (PCS), Laurent Cognet (CPMOH), Brahim Lounis (CPMOH)
Single NanoParticle Photothermal Tracking (SNaPT) of 5 nm gold beads in live cells
null
Biophysical Journal 91, 12 (15/12/2006) 4598
10.1529/biophysj.106.089771
null
physics.bio-ph physics.optics
null
Tracking individual nano-objets in live cells during arbitrary long times is an ubiquitous need in modern biology. We present here a method for tracking individual 5 nm gold nanoparticles on live cells. It relies on the photothermal effect and the detection of the Laser Induced Scattering around a NanoAbsorber (LISNA). The key point for recording trajectories at video rate is the use of a triangulation procedure. The effectiveness of the method is tested against Single fluorescent Molecule Tracking in live COS7 cells on subsecond time scales. We further demonstrate recordings for several minutes of AMPA receptors trajectories on the plasma membrane of live neurons. SNaPT has the unique potential to record arbitrary long trajectory of membrane proteins using non-fluorescent nanometer sized labels.
2007-05-23
0704.3816
Laurent Cognet
Laurent Cognet (CPMOH), Catherine Tardin (CPMOH), David Boyer (CPMOH), Daniel Choquet (PCS), Philippe Tamarat (CPMOH), Brahim Lounis (CPMOH)
Single metallic nanoparticle imaging for protein detection in cells
null
Proceeding of the national academy of sciences 100, 20 (30/09/2003) 11350
10.1073/pnas.1534635100
null
physics.optics physics.bio-ph
null
We performed a visualization of membrane proteins labeled with 10-nm gold nanoparticles in cells, using an all-optical method based on photothermal interference contrast. The high sensitivity of the method and the stability of the signals allows 3D imaging of individual nanoparticles without the drawbacks of photobleaching and blinking inherent to fluorescent markers. A simple analytical model is derived to account for the measurements of the signal amplitude and the spatial resolution. The photothermal interference contrast method provides an efficient, reproducible, and promising way to visualize low amounts of proteins in cells by optical means.
2007-05-23
0704.3826
Mark Ya. Azbel'
Mark Ya. Azbel
Non-coding DNA programs express adaptation and its universal law
Refined version 19 pages, 10 figs
null
null
null
q-bio.GN cond-mat.other nlin.AO q-bio.OT q-bio.PE q-bio.QM
null
Significant fraction (98.5% in humans) of most animal genomes is non- coding dark matter. Its largely unknown function (1-5) is related to programming (rather than to spontaneous mutations) of accurate adaptation to rapidly changing environment. Programmed adaptation to the same universal law for non-competing animals from anaerobic yeast to human is revealed in the study of their extensively quantified mortality (6-21). Adaptation of animals with removed non-coding DNA fractions may specify their contribution to genomic programming. Emergence of new adaptation programs and their (non-Mendelian) heredity may be studied in antibiotic mini-extinctions (22-24). On a large evolutionary scale rapid universal adaptation was vital for survival, and evolved, in otherwise lethal for diverse species major mass extinctions (25-28). Evolutionary and experimental data corroborate these conclusions (6-21, 29-32). Universal law implies certain biological universality of diverse species, thus quantifies applicability of animal models to humans). Genomic adaptation programming calls for unusual approach to its study and implies unanticipated perspectives, in particular, directed biological changes.
2007-08-02
0704.3853
Laurent Cognet
Laurent Cognet (CPMOH), Fran\c{c}oise Coussen (PCS), Daniel Choquet (PCS), Brahim Lounis (CPMOH)
Fluorescence microscopy of single autofluorescent proteins for cellular biology
null
Comptes Rendus de l Acad\'emie des Sciences - Series IV - Physics 3 (15/08/2002) 645
null
null
physics.optics physics.bio-ph
null
In this paper we review the applicability of autofluorescent proteins for single-molecule imaging in biology. The photophysical characteristics of several mutants of the Green Fluorescent Protein (GFP) and those of DsRed are compared and critically discussed for their use in cellular biology. The alternative use of two-photon excitation at the single-molecule level or Fluorescence Correlation Spectroscopy is envisaged for the study of individual autofluorescent proteins. Single-molecule experiments performed in live cells using eGFP and preferably eYFP fusion proteins are reviewed. Finally, the first use at the single-molecule level of citrine, a more photostable variant of the eYFP is reported when fused to a receptor for neurotransmitter in live cells.
2007-05-23
0704.3854
Laurent Cognet
Laurent Cognet (CPMOH), Laurent Groc (PCS), Brahim Lounis (CPMOH), Daniel Choquet (PCS)
Multiple Routes for Glutamate Receptor Trafficking: Surface Diffusion and Membrane Traffic Cooperate to Bring Receptors to Synapses
null
Science's STKE (electronic resource) : signal transduction knowledge environment 327 (21/03/2006) 13
null
null
physics.optics physics.bio-ph
null
Trafficking of glutamate receptors into and out of synapses is critically involved in the plasticity of excitatory synaptic transmission. Endocytosis and exocytosis of receptors have initially been thought to account alone for this trafficking. However, membrane proteins also traffic through surface lateral diffusion in the plasma membrane. We describe developments in electrophysiological and optical approaches that have allowed for the real time measurement of glutamate receptor surface trafficking in live neurons. These include (i) specific imaging of surface receptors using a pH sensitive fluorescent protein, (ii) design of a photoactivable drug to inactivate locally surface receptors and monitor electrophysiologically their recovery, and (iii)application of single molecule fluorescence microscopy to directly track the movement of individual surface receptors with nanometer resolution inside and outside synapses. Altogether, these approaches have demonstrated that glutamate receptors diffuse at high rates in the neuronal membrane and suggest a key role for surface diffusion in the regulation of receptor numbers at synapses.
2007-05-23
0704.3855
Laurent Cognet
Piet H M Lommerse, Gerhard A Blab, Laurent Cognet, Gregory S Harms, B Ewa Snaar-Jagalska, Herman P Spaink, Thomas Schmidt
Single-molecule imaging of the H-ras membrane-anchor reveals domains in the cytoplasmic leaflet of the cell membrane
null
Biophys J 86, 1 Pt 1 (01/2004) 609-16
null
null
physics.optics physics.bio-ph
null
In the last decade evidence has accumulated that small domains of 50-700 nm in diameter are located in the exoplasmic leaflet of the plasma membrane. Most of these domains supposedly consist of specific sets of lipids and proteins, and are believed to coordinate signal transduction cascades. Whether similar domains are also present in the cytoplasmic leaflet of the plasma membrane is unclear so far. To investigate the presence of cytoplasmic leaflet domains, the H-Ras membrane-targeting sequence was fused to the C-terminus of the enhanced yellow fluorescent protein. Using single-molecule fluorescence microscopy, trajectories of individual molecules diffusing in the cytoplasmic leaflet of the plasma membrane were recorded. From these trajectories, the diffusion of individual membrane-anchored enhanced yellow fluorescent protein molecules was studied in live cells on timescales from 5 to 200 ms. The results show that the diffusion of 30-40% of the molecules is constrained in domains with a typical size of 200 nm. Neither breakdown of actin nor cholesterol extraction changed the domain characteristics significantly, indicating that the observed domains may not be related to the membrane domains identified so far.
2007-05-23
0704.3858
Laurent Cognet
Catherine Tardin (CPMOH), Laurent Cognet (CPMOH), C\'ecile Bats (PCS), Brahim Lounis (CPMOH), Daniel Choquet (PCS)
Direct imaging of lateral movements of AMPA receptors inside synapses
null
EMBO J 22, 18 (15/09/2003) 4656-65
10.1093/emboj/cdg463
null
physics.optics physics.bio-ph
null
Trafficking of AMPA receptors in and out of synapses is crucial for synaptic plasticity. Previous studies have focused on the role of endo/exocytosis processes or that of lateral diffusion of extra-synaptic receptors. We have now directly imaged AMPAR movements inside and outside synapses of live neurons using single-molecule fluorescence microscopy. Inside individual synapses, we found immobile and mobile receptors, which display restricted diffusion. Extra-synaptic receptors display free diffusion. Receptors could also exchange between these membrane compartments through lateral diffusion. Glutamate application increased both receptor mobility inside synapses and the fraction of mobile receptors present in a juxtasynaptic region. Block of inhibitory transmission to favor excitatory synaptic activity induced a transient increase in the fraction of mobile receptors and a decrease in the proportion of juxtasynaptic receptors. Altogether, our data show that rapid exchange of receptors between a synaptic and extra-synaptic localization occurs through regulation of receptor diffusion inside synapses.
2007-05-23
0704.3948
Alexey Mazur K
Alexey K. Mazur
The Worm-Like Chain Theory And Bending Of Short DNA
4 pages, 3 figures, to appear in PRL
Phys. Rev. Lett. 98, 218102, 2007.
10.1103/PhysRevLett.98.218102
null
q-bio.BM cond-mat.soft physics.bio-ph
null
The probability distributions for bending angles in double helical DNA obtained in all-atom molecular dynamics simulations are compared with theoretical predictions. The computed distributions remarkably agree with the worm-like chain theory for double helices of one helical turn and longer, and qualitatively differ from predictions of the semi-elastic chain model. The computed data exhibit only small anomalies in the apparent flexibility of short DNA and cannot account for the recently reported AFM data (Wiggins et al, Nature nanotechnology 1, 137 (2006)). It is possible that the current atomistic DNA models miss some essential mechanisms of DNA bending on intermediate length scales. Analysis of bent DNA structures reveals, however, that the bending motion is structurally heterogeneous and directionally anisotropic on the intermediate length scales where the experimental anomalies were detected. These effects are essential for interpretation of the experimental data and they also can be responsible for the apparent discrepancy.
2009-11-13
0704.3957
Vasily Ogryzko V
Vasily Ogryzko
Erwin Schroedinger, Francis Crick and epigenetic stability
New and improved version of the essay, now published in the online journal 'Biology Direct'. Contains more expanded discussion on entanglement. 18 pages, 2 figures. The file includes open reviews by E.Koonin, V.Vedral and E.Karsenti
Biol Direct. 2008 Apr 17;3(1):15
null
null
physics.gen-ph q-bio.MN
null
Schroedinger's book 'What is Life?' is widely credited for having played a crucial role in development of molecular and cellular biology. My essay revisits the issues raised by this book from the modern perspective of epigenetics and systems biology. I contrast two classes of potential mechanisms of epigenetic stability: 'epigenetic templating' and 'systems biology' approaches, and consider them from the point of view expressed by Schroedinger. I also discuss how quantum entanglement, a nonclassical feature of quantum mechanics, can help to address the 'problem of small numbers' that lead Schroedinger to promote the idea of molecular code-script for explanation of stability of biological order.
2008-05-30
0705.0078
Claudius Gros
Claudius Gros
Neural networks with transient state dynamics
null
New J.Phys.9:109,2007
10.1088/1367-2630/9/4/109
null
cond-mat.dis-nn astro-ph cond-mat.other nlin.AO q-bio.NC
null
We investigate dynamical systems characterized by a time series of distinct semi-stable activity patterns, as they are observed in cortical neural activity patterns. We propose and discuss a general mechanism allowing for an adiabatic continuation between attractor networks and a specific adjoined transient-state network, which is strictly dissipative. Dynamical systems with transient states retain functionality when their working point is autoregulated; avoiding prolonged periods of stasis or drifting into a regime of rapid fluctuations. We show, within a continuous-time neural network model, that a single local updating rule for online learning allows simultaneously (i) for information storage via unsupervised Hebbian-type learning, (ii) for adaptive regulation of the working point and (iii) for the suppression of runaway synaptic growth. Simulation results are presented; the spontaneous breaking of time-reversal symmetry and link symmetry are discussed.
2010-02-11
0705.0201
Jesse Bloom
Jesse D Bloom, Philip A Romero, Zhongyi Lu, and Frances H Arnold
Neutral genetic drift can aid functional protein evolution
null
Biology Direct 2:17 (2007)
10.1186/1745-6150-2-17
null
q-bio.PE q-bio.BM
null
BACKGROUND: Many of the mutations accumulated by naturally evolving proteins are neutral in the sense that they do not significantly alter a protein's ability to perform its primary biological function. However, new protein functions evolve when selection begins to favor other, "promiscuous" functions that are incidental to a protein's biological role. If mutations that are neutral with respect to a protein's primary biological function cause substantial changes in promiscuous functions, these mutations could enable future functional evolution. RESULTS: Here we investigate this possibility experimentally by examining how cytochrome P450 enzymes that have evolved neutrally with respect to activity on a single substrate have changed in their abilities to catalyze reactions on five other substrates. We find that the enzymes have sometimes changed as much as four-fold in the promiscuous activities. The changes in promiscuous activities tend to increase with the number of mutations, and can be largely rationalized in terms of the chemical structures of the substrates. The activities on chemically similar substrates tend to change in a coordinated fashion, potentially providing a route for systematically predicting the change in one function based on the measurement of several others. CONCLUSIONS: Our work suggests that initially neutral genetic drift can lead to substantial changes in protein functions that are not currently under selection, in effect poising the proteins to more readily undergo functional evolution should selection "ask new questions" in the future.
2007-07-18
0705.0227
Graeme J. Ackland
Graeme J. Ackland, Richard D.L.Hanes, Morrel H. Cohen
Self assembly of a model multicellular organism resembling the Dictyostelium slime molds
null
null
null
null
q-bio.CB q-bio.PE
null
The evolution of multicellular organisms from monocellular ancestors represents one of the greatest advances of the history of life. The assembly of such multicellular organisms requires signalling and response between cells: over millions of years these signalling processes have become extremely sophisticated and refined by evolution, such that study of modern organisms may not be able to shed much light on the original ancient processes . Here we are interested in determining how simple a signalling method can be, while still achieving self-assembly. In 2D a coupled cellular automaton/differential equation approach models organisms and chemotaxic chemicals, producing spiralling aggregation. In 3D Lennard-Jones-like particles are used to represent single cells, and their evolution in response to signalling is followed by molecular dynamics. It is found that if a single cell is able to emit a signal which induces others to move towards it, then a colony of single-cell organisms can assemble into shapes as complex as a tower, a ball atop a stalk, or a fast-moving slug. The similarity with the behaviour of modern Dictyostelium slime molds signalling with cyclic adenosine monophosphate (cAMP) is striking.
2007-05-23
0705.0313
Gasper Tkacik
Gasper Tkacik, Curtis G Callan Jr, William Bialek
Information flow and optimization in transcriptional control
5 pages, 4 figures
Proc Natl Acad Sci USA 105 (2008): 12265-12270
10.1073/pnas.0806077105
null
q-bio.MN
null
In the simplest view of transcriptional regulation, the expression of a gene is turned on or off by changes in the concentration of a transcription factor (TF). We use recent data on noise levels in gene expression to show that it should be possible to transmit much more than just one regulatory bit. Realizing this optimal information capacity would require that the dynamic range of TF concentrations used by the cell, the input/output relation of the regulatory module, and the noise levels of binding and transcription satisfy certain matching relations. This parameter-free prediction is in good agreement with recent experiments on the Bicoid/Hunchback system in the early Drosophila embryo, and this system achieves ~90% of its theoretical maximum information transmission.
2013-08-01
0705.0374
Razvan Radulescu M.D.
Razvan T. Radulescu, Angelika Jahn, Daniela Hellmann and Gregor Weirich
Immunohistochemical pitfalls in the demonstration of insulin-degrading enzyme in normal and neoplastic human tissues
17 pages, 6 figures
null
null
null
q-bio.TO q-bio.QM
null
Previously, we have identified the cytoplasmic zinc metalloprotease insulin-degrading enzyme(IDE) in human tissues by an immunohistochemical method involving no antigen retrieval (AR) by pressure cooking to avoid artifacts by endogenous biotin exposure and a detection kit based on the labeled streptavidin biotin (LSAB) method. Thereby, we also employed 3% hydrogen peroxide(H2O2) for the inhibition of endogenous peroxidase activity and incubated the tissue sections with the biotinylated secondary antibody at room temperature (RT). We now add the immunohistochemical details that had led us to this optimized procedure as they also bear a more general relevance when demonstrating intracellular tissue antigens. Our most important result is that endogenous peroxidase inhibition by 0.3% H2O2 coincided with an apparently positive IDE staining in an investigated breast cancer specimen whereas combining a block by 3% H2O2 with an incubation of the biotinylated secondary antibody at RT, yet not at 37 degrees Celsius, revealed this specimen as almost entirely IDE-negative. Our present data caution against three different immunohistochemical pitfalls that might cause falsely positive results and artifacts when using an LSAB- and peroxidase-based detection method: pressure cooking for AR, insufficient quenching of endogenous peroxidases and heating of tissue sections while incubating with biotinylated secondary antibodies.
2007-05-23
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