arXiv
(422,153 recursos)
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Mostrando recursos 161 - 180 de 4,680
161.
Remodeling of biological tissue: Mechanically induced reorientation of a
transversely isotropic chain network - Kuhl, E.; Garikipati, K.; Arruda, E. M.; Grosh, K.
A new class of micromechanically motivated chain network models for soft
biological tissues is presented. On the microlevel, it is based on the
statistics of long chain molecules. A wormlike chain model is applied to
capture the behavior of the collagen microfibrils. On the macrolevel, the
network of collagen chains is represented by a transversely isotropic eight
chain unit cell introducing one characteristic material axis. Biomechanically
induced remodeling is captured by allowing for a continuous reorientation of
the predominant unit cell axis driven by a biomechanical stimulus. To this end,
we adopt the gradual alignment of the unit cell axis with the direction of
maximum principal strain. The evolution...
162.
Opportunistic infection as a cause of transient viremia in chronically
infected HIV patients under treatment with HAART - Jones, Laura E.; Perelson, Alan S.
When highly active antiretroviral therapy is administered for long periods of
time to HIV-1 infected patients, most patients achieve viral loads that are
``undetectable'' by standard assay (i.e., HIV-1 RNA $ < 50$ copies/ml). Yet
despite exhibiting sustained viral loads below the level of detection, a number
of these patients experience unexplained episodes of transient viremia or viral
"blips". We propose here that transient activation of the immune system by
opportunistic infection may explain these episodes of viremia. Indeed, immune
activation by opportunistic infection may spur HIV replication, replenish viral
reservoirs and contribute to accelerated disease progression. In order to
investigate the effects of concurrent infection on chronically infected...
163.
Why high-error-rate random mutagenesis libraries are enriched in
functional and improved proteins - Drummond, D. Allan; Iverson, Brent L.; Georgiou, George; Arnold, Frances H.
Recently, several groups have used error-prone polymerase chain reactions to
construct mutant libraries containing up to 27 nucleotide mutations per gene on
average, and reported a striking observation: although retention of protein
function initially declines exponentially with mutations as has previously been
observed, orders of magnitude more proteins remain viable at the highest
mutation rates than this trend would predict. Mutant proteins having improved
or novel activity were isolated disproportionately from these heavily mutated
libraries, leading to the suggestion that distant regions of sequence space are
enriched in useful cooperative mutations and that optimal mutagenesis should
target these regions. If true, these claims have profound implications for
laboratory evolution and...
164.
Native geometry and the dynamics of protein folding - Faisca, P. F. N.; da Gama, M. M. Telo
In this paper we investigate the role of native geometry on the kinetics of
protein folding based on simple lattice models and Monte Carlo simulations.
Results obtained within the scope of the Miyazawa-Jernigan indicate the
existence of two dynamical folding regimes depending on the protein chain
length. For chains larger than 80 amino acids the folding performance is
sensitive to the native state's conformation. Smaller chains, with less than 80
amino acids, fold via two-state kinetics and exhibit a significant correlation
between the contact order parameter and the logarithmic folding times. In
particular, chains with N=48 amino acids were found to belong to two broad
classes of folding, characterized...
165.
Systematic identification of abundant A-to-I editing sites in the human
transcriptome - Levanon, Erez Y.; Eisenberg, Eli; Yelin, Rodrigo; Nemzer, Sergey; Hallegger, Martina; Shemesh, Ronen; Fligelman, Zipora Y.; Shoshan, Avi; Pollock, Sarah R.; Sztybel, Dan; Olshansky, Moshe; Rechavi, Gideon; Jantsch, Michael F.
RNA editing by members of the double-stranded RNA-specific ADAR family leads
to site-specific conversion of adenosine to inosine (A-to-I) in precursor
messenger RNAs. Editing by ADARs is believed to occur in all metazoa, and is
essential for mammalian development. Currently, only a limited number of human
ADAR substrates are known, while indirect evidence suggests a substantial
fraction of all pre-mRNAs being affected. Here we describe a computational
search for ADAR editing sites in the human transcriptome, using millions of
available expressed sequences. 12,723 A-to-I editing sites were mapped in 1,637
different genes, with an estimated accuracy of 95%, raising the number of known
editing sites by two orders of...
166.
Evolutionary dynamics of adult stem cells: Comparison of random and
immortal strand segregation mechanisms - Tannenbaum, Emmanuel; Sherley, James L.; Shakhnovich, Eugene I.
This paper develops a point-mutation model describing the evolutionary
dynamics of a population of adult stem cells. Such a model may prove useful for
quantitative studies of tissue aging and the emergence of cancer. We consider
two modes of chromosome segregation: (1) Random segregation, where the daughter
chromosomes of a given parent chromosome segregate randomly into the stem cell
and its differentiating sister cell. (2) ``Immortal DNA strand''
co-segregation, for which the stem cell retains the daughter chromosomes with
the oldest parent strands. Immortal strand co-segregation is a mechanism,
originally proposed by Cairns (J. Cairns, {\it Nature} {\bf 255}, 197 (1975)),
by which stem cells preserve the integrity of...
167.
A Statistical Analysis of RNA Folding Algorithms Through Thermodynamic
Parameter Perturbation - Layton, D. M.; Bundschuh, R.
Computational RNA secondary structure prediction is rather well established.
However, such prediction algorithms always depend on a large number of
experimentally measured parameters. Here, we study how sensitive structure
prediction algorithms are to changes in these parameters. We find that already
for changes corresponding to the actual experimental error to which these
parameters have been determined 30% of the structure are falsly predicted and
the ground state structure is preserved under parameter perturbation in only 5%
of all cases. We establish that base pairing probabilities calculated in a
thermal ensemble are a viable though not perfect measure for the reliability of
the prediction of individual structure elements. A new...
168.
Cognitive styles sex the brain, compete neurally, and quantify deficits
in autism - Goldenfeld, Nigel; Wheelwright, Sally; Baron-Cohen, Simon
Introduction: Two key dimensions of the mind are understanding and responding
to another's mental state (empathizing), and analysing lawful behaviour
(systemizing).
Methods: Two questionnaires, the Systemizing Quotient (SQ) and the Empathy
Quotient (EQ), were administered to a normal control group and a group of
individuals with Asperger Syndrome (AS) or High-Functioning Autism (HFA). The
multivariate correlations of the joint scores were analysed using principal
components analysis.
Results: The principal components were well-approximated by the sums and
differences of the SQ and EQ scores. The differences in the scores corresponded
to sex differences within the control group and also separated out the AS/HFA
group, which showed stronger systemizing than the...
169.
A Structured-Population Model of Proteus mirabilis Swarm-Colony
Development - Ayati, Bruce P.
In this paper we present continuous age- and space-structured models and
numerical computations of Proteus mirabilis swarm-colony development. We base
the mathematical representation of the cell-cycle dynamics of Proteus mirabilis
on those developed by Esipov and Shapiro, which are the best understood aspects
of the system, and we make minimum assumptions about less-understood
mechanisms, such as precise forms of the spatial diffusion. The models in this
paper have explicit age-structure and, when solved numerically, display both
the temporal and spatial regularity seen in experiments, whereas the Esipov and
Shapiro model, when solved accurately, shows only the temporal regularity.
The composite hyperbolic-parabolic partial differential equations used to
model Proteus mirabilis...
170.
Looking at structure, stability, and evolution of proteins through the
principal eigenvector of contact matrices and hydrophobicity profiles - Bastolla, Ugo; Porto, Markus; Roman, H. Eduardo; Vendruscolo, Michele
We review and further develop an analytical model that describes how
thermodynamic constraints on the stability of the native state influence
protein evolution in a site-specific manner. To this end, we represent both
protein sequences and protein structures as vectors: Structures are represented
by the principal eigenvector (PE) of the protein contact matrix, a quantity
that resembles closely the effective connectivity of each site; Sequences are
represented through the ``interactivity'' of each amino acid type, using novel
parameters that are correlated with hydropathy scales. These interactivity
parameters are more strongly correlated than the other hydropathy scales that
we examine with: (1) The change upon mutations of the unfolding free...
171.
Transcriptional Regulation by the Numbers 1: Models - Bintu, Lacramioara; Buchler, Nicolas E.; Garcia, Hernan G.; Gerland, Ulrich; Hwa, Terence; Kondev, Jane'; Phillips, Rob
The study of gene regulation and expression is often discussed in
quantitative terms. In particular, the expression of genes is regularly
characterized with respect to how much, how fast, when and where. Whether
discussing the level of gene expression in a bacterium or its precise location
within a developing embryo, the natural language for these experiments is that
of numbers. Such quantitative data demands quantitative models. We review a
class of models ("thermodynamic models") which exploit statistical mechanics to
compute the probability that RNA polymerase is at the appropriate promoter.
This provides a mathematically precise elaboration of the idea that activators
are agents of recruitment which increase the probability...
172.
Transcriptional Regulation by the Numbers 2: Applications - Bintu, Lacramioara; Buchler, Nicolas E.; Garcia, Hernan G.; Gerland, Ulrich; Hwa, Terence; Kondev, Jane'; Kuhlman, Thomas; Phillips, Rob
With the increasing amount of experimental data on gene expression and
regulation, there is a growing need for quantitative models to describe the
data and relate them to the different contexts. The thermodynamic models
reviewed in the preceding paper provide a useful framework for the quantitative
analysis of bacterial transcription regulation. We review a number of
well-characterized bacterial promoters that are regulated by one or two species
of transcription factors, and apply the thermodynamic framework to these
promoters. We show that the framework allows one to quantify vastly different
forms of gene expression using a few parameters. As such, it provides a compact
description useful for higher-level studies, e.g.,...
173.
A double-deletion method to quantifying incremental binding energies in
proteins from experiment. Example of a destabilizing hydrogen bonding pair - Campos, Luis A.; Cuesta-Lopez, Santiago; Lopez-Llano, Jon; Falo, Fernando; Sancho, Javier
The contribution of a specific hydrogen bond in apoflavodoxin to protein
stability is investigated by combining theory, experiment and simulation.
Although hydrogen bonds are major determinants of protein structure and
function, their contribution to protein stability is still unclear and widely
debated. The best method so far devised to estimate the contribution of
side-chain interactions to protein stability is double-mutant-cycle analysis,
but the interaction energies so derived are not identical to incremental
binding energies (the energies quantifying net contributions of two interacting
groups to protein stability). Here we introduce double-deletion analysis of
isolated residue pairs as a means to precisely quantify incremental binding.
The method is exemplified by studying a...
174.
A one-dimensional Lattice Boltzmann method for modeling the dynamic
pole-to-pole oscillations of Min proteins for determining the position of the
midcell division plane - Ngamsaad, Waipot; Triampo, Wannapong; Kanthang, Paisan; Tang, I-Ming; Nuttawut, Narin; Modjung, Charin
Determining the middle of the bacteria cell and the proper placement of the
septum is essential to the division of the bacterial cell. In E. coli, this
process depends on the proteins MinC, MinD, and MinE. Here, the Lattice
Boltzmann method (LBM) is used to study the dynamics of the oscillations of the
min proteins from pole to pole. This determines the midcell division plane at
the cellular level. The LBM is applied to the set of the deterministic reaction
diffusion equations proposed by Howard et. al. [1] to describe the dynamics of
the Min proteins. The LBM results are in good agreement with those of Howard...
175.
A New DNA Sequences Vector Space on a Genetic Code Galois Field - Sanchez, Robersy; Perfetti, Luis A.; Grau, Ricardo; Morgado, Eberto
A new n-dimensional vector space of the DNA sequences on the Galois field of
the 64 codons (GF(64)) is proposed. In this vector space gene mutations can be
considered linear transformations or translations of the wild type gene. In
particular, the set of translations that preserve the chemical type of the
third base position in the codon is a subgroup which describes the most
frequent mutations observed in mutational variants of four genes: human
phenylalanine hydroxylase (PAH), human beta globin (HBG), HIV-1 Protease (HIVP)
and HIV-1 Reverse transcriptase (HIVRT). Furthermore, an inner pseudo-product
defined between codons tends to have a positive value when the codons code to
similar amino...
176.
The dynamics of the min proteins of Escherichia coli under the constant
external fields - Kanthang, Paisan; Ngamsaad, Waipot; Modchang, Charin; Triampo, Wannapong; Nuttawut, Narin; Tang, I-Ming; Lenbury, Yongwimol
In E. coli the determination of the middle of the cell and the proper
placement of the septum is essential to the division of the cell. This step
depends on the proteins MinC, MinD, and MinE. Exposure to a constant external
field e.g., an electric field or magnetic field may cause the bacteria cell
division mechanism to change resulting in an abnormal cytokinesis. To have
insight into the effects of an external field on this process, we model the
process using a set of the deterministic reaction diffusion equations, which
incorporate the influence of an external field, min protein reactions, and
diffusion of all species. Using the numerical...
177.
Conformational transformations of DNA macromolecule in heteronomous
conformation - Kanevska, P. P.; Volkov, S. N.
To understand the mechanism of TATA-box conformational transformations we
model structure mobility and find the types of conformational excitations of
DNA macromolecule in heteronomous conformation. We have constructed the
two-component model for describing DNA conformational transformation with
simultaneous transitions in the furanos rings of the monomer link. Internal
component describes the change of the base pair position in the double helix.
External component describes the displacement of mass center of the monomer
link. Nonlinearity of the system is accounted with a form of potential energy
describing C3'-C2' and C2'-C3' sugars transitions in monomer link, and
interrelation between monomer conformational transition and macromolecule
deformation. The comparison of our results with experimental...
178.
Forcing reversibility in the no strand-bias substitution model allows
for the theoretical and practical identifiability of its 5 parameters from
pairwise DNA sequence comparisons - Zagordi, O.; Lobry, J. R.
Because of the base pairing rules in DNA, some mutations experienced by a
portion of DNA during its evolution result in the same substitution, as we can
only observe differences in coupled nucleotides. Then, in the absence of a bias
between the two DNA strands, a model with at most 6 different parameters
instead of 12 is sufficient to study the evolutionary relationship between
homologous sequences derived from a common ancestor. On the other hand the same
symmetry reduces the number of independent observations which can be made. Such
a reduction can in some cases invalidate the calculation of the parameters. A
compromise between biologically acceptable hypotheses and...
179.
Tradeoff between short-term and long-term adaptation in a changing
environment - Forster, Robert; Wilke, Claus O.
We investigate the competition dynamics of two microbial or viral strains
that live in an environment that switches periodically between two states. One
of the strains is adapted to the long-term environment, but pays a short-term
cost, while the other is adapted to the short-term environment and pays a cost
in the long term. We explore the tradeoff between these alternative strategies
in extensive numerical simulations, and present a simple analytic model that
can predict the outcome of these competitions as a function of the mutation
rate and the time scale of the environmental changes. Our model is relevant for
arboviruses, which alternate between different host species on...
180.
Love before Sex - Abdullah, Wan Ahmad Tajuddin Wan
Much has been debated about the benefit of sexual over asexual reproduction
in terms of evolutionary fitness. Here we focus on the advantage that may be
brought about by the process of mating, where the choosing of mates contributes
to the increase in fitness in a constructive way. We carry out computer
simulations of such mating systems and investigate, on one hand, how mate
phenotypes contribute to offspring fitness, and, on the other hand, how
selection affects mate phenotypes. We discuss how helpful such a mechanism may
be in determining trajectories on rugged energy landscapes leading to global
optimum.
161.
