2,274 research outputs found
Hebb and the art of spine remodeling
The notion that synaptic remodeling underlies certain forms of learning is one of the main tenets of Hebb's inspiring theories dating from the 1940s. Until recently, however, direct evidence for tight relationships between synaptic remodeling and behavior has been scarce. Fascinating data from recent studies on the remodeling of postsynaptic structures known as dendritic spines indicates that such relationships might be more complex than initially expected
Serially-regulated biological networks fully realize a constrained set of functions
We show that biological networks with serial regulation (each node regulated
by at most one other node) are constrained to {\it direct functionality}, in
which the sign of the effect of an environmental input on a target species
depends only on the direct path from the input to the target, even when there
is a feedback loop allowing for multiple interaction pathways. Using a
stochastic model for a set of small transcriptional regulatory networks that
have been studied experimentally, we further find that all networks can achieve
all functions permitted by this constraint under reasonable settings of
biochemical parameters. This underscores the functional versatility of the
networks.Comment: 9 pages, 3 figure
Relation between stress heterogeneity and aftershock rate in the rate-and-state model
We estimate the rate of aftershocks triggered by a heterogeneous stress
change, using the rate-and-state model of Dieterich [1994].We show that an
exponential stress distribution Pt(au) ~exp(-tautau_0) gives an Omori law decay
of aftershocks with time ~1/t^p, with an exponent p=1-A sigma_n/tau_0, where A
is a parameter of the rate-and-state friction law, and \sigma_n the normal
stress. Omori exponent p thus decreases if the stress "heterogeneity" tau_0
decreases. We also invert the stress distribution P(tau) from the seismicity
rate R(t), assuming that the stress does not change with time. We apply this
method to a synthetic stress map, using the (modified) scale invariant "k^2"
slip model [Herrero and Bernard, 1994]. We generate synthetic aftershock
catalogs from this stress change.The seismicity rate on the rupture area shows
a huge increase at short times, even if the stress decreases on average.
Aftershocks are clustered in the regions of low slip, but the spatial
distribution is more diffuse than for a simple slip dislocation. Because the
stress field is very heterogeneous, there are many patches of positive stress
changes everywhere on the fault.This stochastic slip model gives a Gaussian
stress distribution, but nevertheless produces an aftershock rate which is very
close to Omori's law, with an effective p<=1, which increases slowly with time.
We obtain a good estimation of the stress distribution for realistic catalogs,
when we constrain the shape of the distribution. However, there are probably
other factors which also affect the temporal decay of aftershocks with time. In
particular, heterogeneity of A\sigma_n can also modify the parameters p and c
of Omori's law. Finally, we show that stress shadows are very difficult to
observe in a heterogeneous stress context.Comment: In press in JG
Biological interaction networks are conserved at the module level
<p>Abstract</p> <p>Background</p> <p>Orthologous genes are highly conserved between closely related species and biological systems often utilize the same genes across different organisms. However, while sequence similarity often implies functional similarity, interaction data is not well conserved even for proteins with high sequence similarity. Several recent studies comparing high throughput data including expression, protein-protein, protein-DNA, and genetic interactions between close species show conservation at a much lower rate than expected.</p> <p>Results</p> <p>In this work we collected comprehensive high-throughput interaction datasets for four model organisms (<it>S. cerevisiae, S. pombe, C. elegans</it>, and <it>D. melanogaster</it>) and carried out systematic analyses in order to explain the apparent lower conservation of interaction data when compared to the conservation of sequence data. We first showed that several previously proposed hypotheses only provide a limited explanation for such lower conservation rates. We combined all interaction evidences into an integrated network for each species and identified functional modules from these integrated networks. We then demonstrate that interactions that are part of functional modules are conserved at much higher rates than previous reports in the literature, while interactions that connect between distinct functional modules are conserved at lower rates.</p> <p>Conclusions</p> <p>We show that conservation is maintained between species, but mainly at the module level. Our results indicate that interactions within modules are much more likely to be conserved than interactions between proteins in different modules. This provides a network based explanation to the observed conservation rates that can also help explain why so many biological processes are well conserved despite the lower levels of conservation for the interactions of proteins participating in these processes.</p> <p>Accompanying website: <url>http://www.sb.cs.cmu.edu/CrossSP</url></p
Multiple breast cancer risk variants are associated with differential transcript isoform expression in tumors.
Genome-wide association studies have identified over 70 single-nucleotide polymorphisms (SNPs) associated with breast cancer. A subset of these SNPs are associated with quantitative expression of nearby genes, but the functional effects of the majority remain unknown. We hypothesized that some risk SNPs may regulate alternative splicing. Using RNA-sequencing data from breast tumors and germline genotypes from The Cancer Genome Atlas, we tested the association between each risk SNP genotype and exon-, exon-exon junction- or transcript-specific expression of nearby genes. Six SNPs were associated with differential transcript expression of seven nearby genes at FDR < 0.05 (BABAM1, DCLRE1B/PHTF1, PEX14, RAD51L1, SRGAP2D and STXBP4). We next developed a Bayesian approach to evaluate, for each SNP, the overlap between the signal of association with breast cancer and the signal of association with alternative splicing. At one locus (SRGAP2D), this method eliminated the possibility that the breast cancer risk and the alternate splicing event were due to the same causal SNP. Lastly, at two loci, we identified the likely causal SNP for the alternative splicing event, and at one, functionally validated the effect of that SNP on alternative splicing using a minigene reporter assay. Our results suggest that the regulation of differential transcript isoform expression is the functional mechanism of some breast cancer risk SNPs and that we can use these associations to identify causal SNPs, target genes and the specific transcripts that may mediate breast cancer risk
Efficient LZ78 factorization of grammar compressed text
We present an efficient algorithm for computing the LZ78 factorization of a
text, where the text is represented as a straight line program (SLP), which is
a context free grammar in the Chomsky normal form that generates a single
string. Given an SLP of size representing a text of length , our
algorithm computes the LZ78 factorization of in time
and space, where is the number of resulting LZ78 factors.
We also show how to improve the algorithm so that the term in the
time and space complexities becomes either , where is the length of the
longest LZ78 factor, or where is a quantity
which depends on the amount of redundancy that the SLP captures with respect to
substrings of of a certain length. Since where
is the alphabet size, the latter is asymptotically at least as fast as
a linear time algorithm which runs on the uncompressed string when is
constant, and can be more efficient when the text is compressible, i.e. when
and are small.Comment: SPIRE 201
Dynamic Fluctuation Phenomena in Double Membrane Films
Dynamics of double membrane films is investigated in the long-wavelength
limit including the overdamped squeezing mode. We demonstrate that thermal
fluctuations essentially modify the character of the mode due to its nonlinear
coupling to the transversal shear hydrodynamic mode. The corresponding Green
function acquires as a function of the frequency a cut along the imaginary
semi-axis. Fluctuations lead to increasing the attenuation of the squeezing
mode it becomes larger than the `bare' value.Comment: 7 pages, Revte
Synapse integrity and function: Dependence on protein synthesis and identification of potential failure points
Synaptic integrity and function depend on myriad proteins - labile molecules with finite lifetimes that need to be continually replaced with freshly synthesized copies. Here we describe experiments designed to expose synaptic (and neuronal) properties and functions that are particularly sensitive to disruptions in protein supply, identify proteins lost early upon such disruptions, and uncover potential, yet currently underappreciated failure points. We report here that acute suppressions of protein synthesis are followed within hours by reductions in spontaneous network activity levels, impaired oxidative phosphorylation and mitochondrial function, and, importantly, destabilization and loss of both excitatory and inhibitory postsynaptic specializations. Conversely, gross impairments in presynaptic vesicle recycling occur over longer time scales (days), as does overt cell death. Proteomic analysis identified groups of potentially essential ‘early-lost’ proteins including regulators of synapse stability, proteins related to bioenergetics, fatty acid and lipid metabolism, and, unexpectedly, numerous proteins involved in Alzheimer’s disease pathology and amyloid beta processing. Collectively, these findings point to neuronal excitability, energy supply and synaptic stability as early-occurring failure points under conditions of compromised supply of newly synthesized protein copies
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