803 research outputs found
Stochastic theory of large-scale enzyme-reaction networks: Finite copy number corrections to rate equation models
Chemical reactions inside cells occur in compartment volumes in the range of
atto- to femtolitres. Physiological concentrations realized in such small
volumes imply low copy numbers of interacting molecules with the consequence of
considerable fluctuations in the concentrations. In contrast, rate equation
models are based on the implicit assumption of infinitely large numbers of
interacting molecules, or equivalently, that reactions occur in infinite
volumes at constant macroscopic concentrations. In this article we compute the
finite-volume corrections (or equivalently the finite copy number corrections)
to the solutions of the rate equations for chemical reaction networks composed
of arbitrarily large numbers of enzyme-catalyzed reactions which are confined
inside a small sub-cellular compartment. This is achieved by applying a
mesoscopic version of the quasi-steady state assumption to the exact
Fokker-Planck equation associated with the Poisson Representation of the
chemical master equation. The procedure yields impressively simple and compact
expressions for the finite-volume corrections. We prove that the predictions of
the rate equations will always underestimate the actual steady-state substrate
concentrations for an enzyme-reaction network confined in a small volume. In
particular we show that the finite-volume corrections increase with decreasing
sub-cellular volume, decreasing Michaelis-Menten constants and increasing
enzyme saturation. The magnitude of the corrections depends sensitively on the
topology of the network. The predictions of the theory are shown to be in
excellent agreement with stochastic simulations for two types of networks
typically associated with protein methylation and metabolism.Comment: 13 pages, 4 figures; published in The Journal of Chemical Physic
How accurate are the non-linear chemical Fokker-Planck and chemical Langevin equations?
The chemical Fokker-Planck equation and the corresponding chemical Langevin
equation are commonly used approximations of the chemical master equation.
These equations are derived from an uncontrolled, second-order truncation of
the Kramers-Moyal expansion of the chemical master equation and hence their
accuracy remains to be clarified. We use the system-size expansion to show that
chemical Fokker-Planck estimates of the mean concentrations and of the variance
of the concentration fluctuations about the mean are accurate to order
for reaction systems which do not obey detailed balance and at
least accurate to order for systems obeying detailed balance,
where is the characteristic size of the system. Hence the chemical
Fokker-Planck equation turns out to be more accurate than the linear-noise
approximation of the chemical master equation (the linear Fokker-Planck
equation) which leads to mean concentration estimates accurate to order
and variance estimates accurate to order . This
higher accuracy is particularly conspicuous for chemical systems realized in
small volumes such as biochemical reactions inside cells. A formula is also
obtained for the approximate size of the relative errors in the concentration
and variance predictions of the chemical Fokker-Planck equation, where the
relative error is defined as the difference between the predictions of the
chemical Fokker-Planck equation and the master equation divided by the
prediction of the master equation. For dimerization and enzyme-catalyzed
reactions, the errors are typically less than few percent even when the
steady-state is characterized by merely few tens of molecules.Comment: 39 pages, 3 figures, accepted for publication in J. Chem. Phy
The potential for linking cohort participants to official criminal records:a pilot study using the Avon Longitudinal Study of Parents and Children (ALSPAC)
Introduction: Linking longitudinal cohort resources with police-recorded records of criminal activity has the potential to inform public health style approaches to policing, and may reduce potential sources of bias from self-reported criminal data collected by cohort studies. A pilot linkage of police records to the Avon Longitudinal Study of Parents and Children (ALSPAC) allows us to consider the acceptability of this linkage, its utility as a data resource, differences in self-reported crime according to consent status for data linkage, and the appropriate governance mechanism to support such a linkage. Methods: We carried out a pilot study linking data from the ALSPAC birth cohort to Ministry of Justice (MoJ) records on criminal cautions and convictions. This pilot was conducted on a fully anonymous basis, meaning we cannot link the identified records to any participant or the wider information within the dataset. Using ALSPAC data, we used summary statistics to investigate differences in socio-economic background and self-reported criminal activity by consent status for crime linkage. We used MoJ records to identify the geographic and temporal concentration of criminality in the ALSPAC cohort. Results: We found that the linkage appears acceptable to participants (4% of the sample opted out), levels of criminal caution and conviction are high enough to support research, and that the majority of crimes occurred in Avon & Somerset (the policing area local to ALSPAC). Those who did not respond to consent requests had higher levels of self-reported criminal behaviour compared to participants who provided explicit consent. Conclusions: These findings suggest that data linkage in ALSPAC provides opportunities to study criminal behaviour and that linked individual-level records could provide robust research in the area. Our findings also suggest the potential for bias when only including participants who have explicitly consented to data linkage, highlighting the limitations of opt-in consent strategies
TeV Particle Astrophysics II: Summary comments
A unifying theme of this conference was the use of different approaches to
understand astrophysical sources of energetic particles in the TeV range and
above. In this summary I review how gamma-ray astronomy, neutrino astronomy and
(to some extent) gravitational wave astronomy provide complementary avenues to
understanding the origin and role of high-energy particles in energetic
astrophysical sources.Comment: 6 pages, 4 figures; Conference summary talk for "TeV Particle
Astrophysics II" at University of Wisconsin, Madison, 28-31 August 200
A stochastic automaton shows how enzyme assemblies may contribute to metabolic efficiency
<p>Abstract</p> <p>Background</p> <p>The advantages of grouping enzymes into metabolons and into higher order structures have long been debated. To quantify these advantages, we have developed a stochastic automaton that allows experiments to be performed in a virtual bacterium with both a membrane and a cytoplasm. We have investigated the general case of transport and metabolism as inspired by the phosphoenolpyruvate:sugar phosphotransferase system (PTS) for glucose importation and by glycolysis.</p> <p>Results</p> <p>We show that PTS and glycolytic metabolons can increase production of pyruvate eightfold at low concentrations of phosphoenolpyruvate. A fourfold increase in the numbers of enzyme EI led to a 40% increase in pyruvate production, similar to that observed <it>in vivo </it>in the presence of glucose. Although little improvement resulted from the assembly of metabolons into a hyperstructure, such assembly can generate gradients of metabolites and signaling molecules.</p> <p>Conclusion</p> <p><it>in silico </it>experiments may be performed successfully using stochastic automata such as HSIM (Hyperstructure Simulator) to help answer fundamental questions in metabolism about the properties of molecular assemblies and to devise strategies to modify such assemblies for biotechnological ends.</p
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Viability Conditions for a Compartmentalized Protometabolic System: A Semi-Empirical Approach
In this work we attempt to find out the extent to which realistic prebiotic compartments, such as fatty acid vesicles, would constrain the chemical network dynamics that could have sustained a minimal form of metabolism. We combine experimental and simulation results to establish the conditions under which a reaction network with a catalytically closed organization (more specifically, an ()-system) would overcome the potential problem of self-suffocation that arises from the limited accessibility of nutrients to its internal reaction domain. The relationship between the permeability of the membrane, the lifetime of the key catalysts and their efficiency (reaction rate enhancement) turns out to be critical. In particular, we show how permeability values constrain the characteristic time scale of the bounded protometabolic processes. From this concrete and illustrative example we finally extend the discussion to a wider evolutionary context
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