99 research outputs found
Reliability of genetic networks is evolvable
Control of the living cell functions with remarkable reliability despite the
stochastic nature of the underlying molecular networks -- a property presumably
optimized by biological evolution. We here ask to what extent the property of a
stochastic dynamical network to produce reliable dynamics is an evolvable
trait. Using an evolutionary algorithm based on a deterministic selection
criterion for the reliability of dynamical attractors, we evolve dynamical
networks of noisy discrete threshold nodes. We find that, starting from any
random network, reliability of the attractor landscape can often be achieved
with only few small changes to the network structure. Further, the evolvability
of networks towards reliable dynamics while retaining their function is
investigated and a high success rate is found.Comment: 5 pages, 3 figure
Self-Organized Criticality model for Brain Plasticity
Networks of living neurons exhibit an avalanche mode of activity,
experimentally found in organotypic cultures. Here we present a model based on
self-organized criticality and taking into account brain plasticity, which is
able to reproduce the spectrum of electroencephalograms (EEG). The model
consists in an electrical network with threshold firing and activity-dependent
synapse strenghts. The system exhibits an avalanche activity power law
distributed. The analysis of the power spectra of the electrical signal
reproduces very robustly the power law behaviour with the exponent 0.8,
experimentally measured in EEG spectra. The same value of the exponent is found
on small-world lattices and for leaky neurons, indicating that universality
holds for a wide class of brain models.Comment: 4 pages, 3 figure
Chiral Symmetry and Diffractive Neutral Pion Photo- and Electroproduction
We show that diffractive production of a single neutral pion in
photon-induced reactions at high energy is dynamically suppressed due to the
approximate chiral symmetry of QCD. These reactions have been proposed as a
test of the odderon exchange mechanism. We show that the odderon contribution
to the amplitude for such reactions vanishes exactly in the chiral limit. This
result is obtained in a nonperturbative framework and by using PCAC relations
between the amplitudes for neutral pion and axial vector current production.Comment: 22 pages, 7 figure
The effect of scale-free topology on the robustness and evolvability of genetic regulatory networks
We investigate how scale-free (SF) and Erdos-Renyi (ER) topologies affect the
interplay between evolvability and robustness of model gene regulatory networks
with Boolean threshold dynamics. In agreement with Oikonomou and Cluzel (2006)
we find that networks with SFin topologies, that is SF topology for incoming
nodes and ER topology for outgoing nodes, are significantly more evolvable
towards specific oscillatory targets than networks with ER topology for both
incoming and outgoing nodes. Similar results are found for networks with SFboth
and SFout topologies. The functionality of the SFout topology, which most
closely resembles the structure of biological gene networks (Babu et al.,
2004), is compared to the ER topology in further detail through an extension to
multiple target outputs, with either an oscillatory or a non-oscillatory
nature. For multiple oscillatory targets of the same length, the differences
between SFout and ER networks are enhanced, but for non-oscillatory targets
both types of networks show fairly similar evolvability. We find that SF
networks generate oscillations much more easily than ER networks do, and this
may explain why SF networks are more evolvable than ER networks are for
oscillatory phenotypes. In spite of their greater evolvability, we find that
networks with SFout topologies are also more robust to mutations than ER
networks. Furthermore, the SFout topologies are more robust to changes in
initial conditions (environmental robustness). For both topologies, we find
that once a population of networks has reached the target state, further
neutral evolution can lead to an increase in both the mutational robustness and
the environmental robustness to changes in initial conditions.Comment: 16 pages, 15 figure
The putative Tumor Suppressor VILIP-1 Counteracts Epidermal Growth Factor-Induced Epidermal-Mesenchymal Transition in Squamous Carcinoma Cells
Epithelial-mesenchymal transition (EMT) is a crucial step for the acquisition of invasive properties of carcinoma cells during tumor progression. Epidermal growth factor (EGF)-treatment of squamous cell carcinoma (SCC) cells provokes changes in the expression of lineage markers, morphological changes, and a higher invasive and metastatic potential. Here we show that chronic stimulation with EGF induces EMT in skin-derived SCC cell lines along with the down-regulation of the epithelial marker E-cadherin, and of the putative tumor suppressor VILIP-1 (visinin-like protein 1). In esophageal squamous cell carcinoma and non-small cell lung carcinoma the loss of VILIP-1 correlates with clinicopathological features related to enhanced invasiveness. VILIP-1 has previously been shown to suppress tumor cell invasion via enhancing cAMP-signaling in a murine SCC model. In mouse skin SCC cell lines the VILIP-1-negative tumor cells have low cAMP levels, whereas VILIP-1-positive SCCs possess high cAMP levels, but low invasive properties. We show that in VILIP-1-negative SCCs, Snail1, a transcriptional repressor involved in EMT, is up-regulated. Snail1 expression is reduced by ectopic VILIP-1-expression in VILIP-1-negative SCC cells, and application of the general adenylyl cyclase inhibitor 2′,3′-dideoxyadenosine attenuated this effect. Conversely, EGF-stimulation of VILIP-1-positive SCC cells leads to the down-regulation of VILIP-1 and the induction of Snail1 expression. The induction of Snail is inhibited by elevated cAMP levels. The role of cAMP in EMT was further highlighted by its suppressive effect on the EGF-induced enhancement of migration in VILIP-1-positive SCC cells. These findings indicate that VILIP-1 is involved in EMT of SCC by regulating the transcription factor Snail1 in a cAMP-dependent manner
Boolean network model predicts cell cycle sequence of fission yeast
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.Comment: 10 pages, 3 figure
Odderon in baryon-baryon scattering from the AdS/CFT correspondence
Based on the AdS/CFT correspondence, we present a holographic description of
various C-odd exchanges in high energy baryon-baryon and baryon-antibaryon
scattering, and calculate their respective contributions to the difference in
the total cross sections. We predict that, due to the warp factor of AdS_5, the
total cross section in pp collisions is larger than in p\bar{p} collisions at
asymptotically high energies.Comment: 23 pages, v2: minor changes, to be published in JHE
Quantifying evolvability in small biological networks
We introduce a quantitative measure of the capacity of a small biological
network to evolve. We apply our measure to a stochastic description of the
experimental setup of Guet et al. (Science 296:1466, 2002), treating chemical
inducers as functional inputs to biochemical networks and the expression of a
reporter gene as the functional output. We take an information-theoretic
approach, allowing the system to set parameters that optimize signal processing
ability, thus enumerating each network's highest-fidelity functions. We find
that all networks studied are highly evolvable by our measure, meaning that
change in function has little dependence on change in parameters. Moreover, we
find that each network's functions are connected by paths in the parameter
space along which information is not significantly lowered, meaning a network
may continuously change its functionality without losing it along the way. This
property further underscores the evolvability of the networks.Comment: 8 pages, 3 figure
VILIP-1 Downregulation in Non-Small Cell Lung Carcinomas: Mechanisms and Prediction of Survival
VILIP-1, a member of the neuronal Ca++ sensor protein family, acts as a tumor suppressor gene in an experimental animal model by inhibiting cell proliferation, adhesion and invasiveness of squamous cell carcinoma cells. Western Blot analysis of human tumor cells showed that VILIP-1 expression was undetectable in several types of human tumor cells, including 11 out of 12 non-small cell lung carcinoma (NSCLC) cell lines. The down-regulation of VILIP-1 was due to loss of VILIP-1 mRNA transcripts. Rearrangements, large gene deletions or mutations were not found. Hypermethylation of the VILIP-1 promoter played an important role in gene silencing. In most VILIP-1-silent cells the VILIP-1 promoter was methylated. In vitro methylation of the VILIP-1 promoter reduced its activity in a promoter-reporter assay. Transcriptional activity of endogenous VILIP-1 promoter was recovered by treatment with 5′-aza-2′-deoxycytidine (5′-Aza-dC). Trichostatin A (TSA), a histone deacetylase inhibitor, potently induced VILIP-1 expression, indicating that histone deacetylation is an additional mechanism of VILIP-1 silencing. TSA increased histone H3 and H4 acetylation in the region of the VILIP-1 promoter. Furthermore, statistical analysis of expression and promoter methylation (n = 150 primary NSCLC samples) showed a significant relationship between promoter methylation and protein expression downregulation as well as between survival and decreased or absent VILIP-1 expression in lung cancer tissues (p<0.0001). VILIP-1 expression is silenced by promoter hypermethylation and histone deacetylation in aggressive NSCLC cell lines and primary tumors and its clinical evaluation could have a role as a predictor of short-term survival in lung cancer patients
Sparse canonical correlation analysis for identifying, connecting and completing gene-expression networks
<p>Abstract</p> <p>Background</p> <p>We generalized penalized canonical correlation analysis for analyzing microarray gene-expression measurements for checking completeness of known metabolic pathways and identifying candidate genes for incorporation in the pathway. We used Wold's method for calculation of the canonical variates, and we applied ridge penalization to the regression of pathway genes on canonical variates of the non-pathway genes, and the elastic net to the regression of non-pathway genes on the canonical variates of the pathway genes.</p> <p>Results</p> <p>We performed a small simulation to illustrate the model's capability to identify new candidate genes to incorporate in the pathway: in our simulations it appeared that a gene was correctly identified if the correlation with the pathway genes was 0.3 or more. We applied the methods to a gene-expression microarray data set of 12, 209 genes measured in 45 patients with glioblastoma, and we considered genes to incorporate in the glioma-pathway: we identified more than 25 genes that correlated > 0.9 with canonical variates of the pathway genes.</p> <p>Conclusion</p> <p>We concluded that penalized canonical correlation analysis is a powerful tool to identify candidate genes in pathway analysis.</p
- …