3,514 research outputs found
Cooperative protein transport in cellular organelles
Compartmentalization into biochemically distinct organelles constantly
exchanging material is one of the hallmarks of eukaryotic cells. In the most
naive picture of inter-organelle transport driven by concentration gradients,
concentration differences between organelles should relax. We determine the
conditions under which cooperative transport, i.e. based on molecular
recognition, allows for the existence and maintenance of distinct organelle
identities. Cooperative transport is also shown to control the flux of material
transiting through a compartmentalized system, dramatically increasing the
transit time under high incoming flux. By including chemical processing of the
transported species, we show that this property provides a strong functional
advantage to a system responsible for protein maturation and sorting.Comment: 9 pages, 5 figure
Functional Genomics of Brain Aging and Alzheimer’s Disease: Focus on Selective Neuronal Vulnerability
Pivotal brain functions, such as neurotransmission, cognition, and memory, decline with advancing age and, especially, in neurodegenerative conditions associated with aging, such as Alzheimer’s disease (AD). Yet, deterioration in structure and function of the nervous system during aging or in AD is not uniform throughout the brain. Selective neuronal vulnerability (SNV) is a general but sometimes overlooked characteristic of brain aging and AD. There is little known at the molecular level to account for the phenomenon of SNV. Functional genomic analyses, through unbiased whole genome expression studies, could lead to new insights into a complex process such as SNV. Genomic data generated using both human brain tissue and brains from animal models of aging and AD were analyzed in this review. Convergent trends that have emerged from these data sets were considered in identifying possible molecular and cellular pathways involved in SNV. It appears that during normal brain aging and in AD, neurons vulnerable to injury or cell death are characterized by significant decreases in the expression of genes related to mitochondrial metabolism and energy production. In AD, vulnerable neurons also exhibit down-regulation of genes related to synaptic neurotransmission and vesicular transport, cytoskeletal structure and function, and neurotrophic factor activity. A prominent category of genes that are up-regulated in AD are those related to inflammatory response and some components of calcium signaling. These genomic differences between sensitive and resistant neurons can now be used to explore the molecular underpinnings of previously suggested mechanisms of cell injury in aging and AD
Single Molecule Michaelis-Menten Equation beyond Quasi-Static Disorder
The classic Michaelis-Menten equation describes the catalytic activities for
ensembles of enzyme molecules very well. But recent single-molecule experiment
showed that the waiting time distribution and other properties of single enzyme
molecule are not consistent with the prediction based on the viewpoint of
ensemble. It has been contributed to the slow inner conformational changes of
single enzyme in the catalytic processes. In this work we study the general
dynamics of single enzyme in the presence of dynamic disorder. We find that at
two limiting cases, the slow reaction and nondiffusion limits, Michaelis-Menten
equation exactly holds although the waiting time distribution has a
multiexponential decay behaviors in the nondiffusion limit.Particularly, the
classic Michaelis-Menten equation still is an excellent approximation other
than the two limits.Comment: 10 pages, 1 figur
Entropy driven key-lock assembly
The effective interaction between a sphere with an open cavity (lock) and a
spherical macroparticle (key), both immersed in a hard sphere fluid, is studied
by means of Monte Carlo simulations. As a result, a 2d map of the key-lock
effective interaction potential is constructed, which leads to the proposal of
a self-assembling mechanism: there exists trajectories through which the
key-lock pair could assemble avoiding trespassing potential barriers. Hence,
solely the entropic contribution can induce their self-assembling even in the
absence of attractive forces. This study points out the solvent contribution
within the underlying mechanisms of substrate-protein assembly/disassembly
processes, which are important steps of the enzyme catalysis and protein
mediated transport
Non-equilibrium dynamics of gene expression and the Jarzynski equality
In order to express specific genes at the right time, the transcription of
genes is regulated by the presence and absence of transcription factor
molecules. With transcription factor concentrations undergoing constant
changes, gene transcription takes place out of equilibrium. In this paper we
discuss a simple mapping between dynamic models of gene expression and
stochastic systems driven out of equilibrium. Using this mapping, results of
nonequilibrium statistical mechanics such as the Jarzynski equality and the
fluctuation theorem are demonstrated for gene expression dynamics. Applications
of this approach include the determination of regulatory interactions between
genes from experimental gene expression data
Living on the edge of chaos: minimally nonlinear models of genetic regulatory dynamics
Linearized catalytic reaction equations modeling e.g. the dynamics of genetic
regulatory networks under the constraint that expression levels, i.e. molecular
concentrations of nucleic material are positive, exhibit nontrivial dynamical
properties, which depend on the average connectivity of the reaction network.
In these systems the inflation of the edge of chaos and multi-stability have
been demonstrated to exist. The positivity constraint introduces a nonlinearity
which makes chaotic dynamics possible. Despite the simplicity of such minimally
nonlinear systems, their basic properties allow to understand fundamental
dynamical properties of complex biological reaction networks. We analyze the
Lyapunov spectrum, determine the probability to find stationary oscillating
solutions, demonstrate the effect of the nonlinearity on the effective in- and
out-degree of the active interaction network and study how the frequency
distributions of oscillatory modes of such system depend on the average
connectivity.Comment: 11 pages, 5 figure
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