816 research outputs found
Fluctuation-Facilitated Charge Migration along DNA
We propose a model Hamiltonian for charge transfer along the DNA double helix
with temperature driven fluctuations in the base pair positions acting as the
rate limiting factor for charge transfer between neighboring base pairs. We
compare the predictions of the model with the recent work of J.K. Barton and
A.H. Zewail (Proc.Natl.Acad.Sci.USA, {\bf 96}, 6014 (1999)) on the unusual
two-stage charge transfer of DNA.Comment: 4 pages, 2 figure
Exact solution of a linear molecular motor model driven by two-step fluctuations and subject to protein friction
We investigate by analytical means the stochastic equations of motion of a
linear molecular motor model based on the concept of protein friction. Solving
the coupled Langevin equations originally proposed by Mogilner et al. (A.
Mogilner et al., Phys. Lett. {\bf 237}, 297 (1998)), and averaging over both
the two-step internal conformational fluctuations and the thermal noise, we
present explicit, analytical expressions for the average motion and the
velocity-force relationship. Our results allow for a direct interpretation of
details of this motor model which are not readily accessible from numerical
solutions. In particular, we find that the model is able to predict
physiologically reasonable values for the load-free motor velocity and the
motor mobility.Comment: 12 pages revtex, 6 eps-figure
The compositional and evolutionary logic of metabolism
Metabolism displays striking and robust regularities in the forms of
modularity and hierarchy, whose composition may be compactly described. This
renders metabolic architecture comprehensible as a system, and suggests the
order in which layers of that system emerged. Metabolism also serves as the
foundation in other hierarchies, at least up to cellular integration including
bioenergetics and molecular replication, and trophic ecology. The
recapitulation of patterns first seen in metabolism, in these higher levels,
suggests metabolism as a source of causation or constraint on many forms of
organization in the biosphere.
We identify as modules widely reused subsets of chemicals, reactions, or
functions, each with a conserved internal structure. At the small molecule
substrate level, module boundaries are generally associated with the most
complex reaction mechanisms and the most conserved enzymes. Cofactors form a
structurally and functionally distinctive control layer over the small-molecule
substrate. Complex cofactors are often used at module boundaries of the
substrate level, while simpler ones participate in widely used reactions.
Cofactor functions thus act as "keys" that incorporate classes of organic
reactions within biochemistry.
The same modules that organize the compositional diversity of metabolism are
argued to have governed long-term evolution. Early evolution of core
metabolism, especially carbon-fixation, appears to have required few
innovations among a small number of conserved modules, to produce adaptations
to simple biogeochemical changes of environment. We demonstrate these features
of metabolism at several levels of hierarchy, beginning with the small-molecule
substrate and network architecture, continuing with cofactors and key conserved
reactions, and culminating in the aggregation of multiple diverse physical and
biochemical processes in cells.Comment: 56 pages, 28 figure
Observation of the Early Structural Changes Leading to the Formation of Protein Superstructures.
Formation of superstructures in protein aggregation processes has been indicated as a general pathway for several proteins, possibly playing a role in human pathologies. There is a severe lack of knowledge on the origin of such species in terms of both mechanisms of formation and structural features. We use equine lysozyme as a model protein, and by combining spectroscopic techniques and microscopy with X-ray fiber diffraction and ab initio modeling of Small Angle X-ray Scattering data, we isolate the partially unfolded state from which one of these superstructures (i.e., particulate) originates. We reveal the low-resolution structure of the unfolded state and its mechanism of formation, highlighting the physicochemical features and the possible pathway of formation of the particulate structure. Our findings provide a novel detailed knowledge of such a general and alternative aggregation pathway for proteins, this being crucial for a basic and broader understanding of the aggregation phenomena.This is the author's accepted manuscript and will be under embargo until the 3rd of September 2015. The final version is published by ACS in The Journal of Physical Chemistry Letters here: http://pubs.acs.org/doi/abs/10.1021/jz501614e
Two-Photon Fluorescence Microscopy Imaging of Cellular Oxidative Stress Using Profluorescent Nitroxides
A range of varying chromophore nitroxide free radicals and their nonradical methoxyamine analogues were synthesized and their linear photophysical properties examined. The presence of the proximate free radical masks the chromophoreâs usual fluorescence emission, and these species are described as profluorescent. Two nitroxides incorporating anthracene and fluorescein chromophores (compounds 7 and 19, respectively) exhibited two-photon absorption (2PA) cross sections of approximately 400 G.M. when excited at wavelengths greater than 800 nm. Both of these profluorescent nitroxides demonstrated low cytotoxicity toward Chinese hamster ovary (CHO) cells. Imaging colocalization experiments with the commercially available CellROX Deep Red oxidative stress monitor demonstrated good cellular uptake of the nitroxide probes. Sensitivity of the nitroxide probes to H2O2-induced damage was also demonstrated by both one- and two-photon fluorescence microscopy. These profluorescent nitroxide probes are potentially powerful tools for imaging oxidative stress in biological systems, and they essentially âlight upâ in the presence of certain species generated from oxidative stress. The high ratio of the fluorescence quantum yield between the profluorescent nitroxide species and their nonradical adducts provides the sensitivity required for measuring a range of cellular redox environments. Furthermore, their reasonable 2PA cross sections provide for the option of using two-photon fluorescence microscopy, which circumvents commonly encountered disadvantages associated with one-photon imaging such as photobleaching and poor tissue penetration
Fluctuation Induced Homochirality
We propose a new mechanism for the achievment of homochirality in life
without any autocatalytic production process. Our model consists of a
spontaneous production together with a recycling cross inhibition in a closed
system.
It is shown that although the rate equations for this system predict no
chiral symmetry breaking, the stochastic master equation predicts complete
homochirality. This is because the fluctuation induced by the discreteness of
population numbers of participating molecules plays essential roles. This
fluctuation conspires with the recyling cross inhibition to realize the
homochirality.Comment: 13 pages, 6 figure
The effect of adenosine monophosphate deaminase overexpression on the accumulation of umami-related metabolites in tomatoes
Taste is perceived as one of a combination of five sensations, sweet, sour, bitter, salty, and umami. The umami taste is best known as a savoury sensation and plays a central role in food flavour, palatability, and eating satisfaction. Umami flavour can be imparted by the presence of glutamate and is greatly enhanced by the addition of ribonucleotides, such as inosine monophosphate (IMP) and guanosine monophosphate (GMP). The production of IMP is regulated by the enzyme adenosine monophosphate (AMP) deaminase which functions to convert AMP into IMP. We have generated transgenic tomato (Solanum lycopersicum) lines over expressing AMP deaminase under the control of a fruit-specific promoter. The transgenic lines showed substantially enhanced levels of AMP deaminase expression in comparison to the wild-type control. Elevated AMP deaminase levels resulted in the reduced accumulation of glutamate and increased levels of the umami nucleotide GMP. AMP concentrations were unchanged. The effects on the levels of glutamate and GMP were unexpected and are discussed in relation to the metabolite flux within this pathway
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