1,233 research outputs found
Stochastic approach to molecular interactions and computational theory of metabolic and genetic regulations
Binding and unbinding of ligands to specific sites of a macromolecule are one
of the most elementary molecular interactions inside the cell that embody the
computational processes of biological regulations. The interaction between
transcription factors and the operators of genes and that between ligands and
binding sites of allosteric enzymes are typical examples of such molecular
interactions. In order to obtain the general mathematical framework of
biological regulations, we formulate these interactions as finite Markov
processes and establish a computational theory of regulatory activities of
macromolecules based mainly on graphical analysis of their state transition
diagrams. The contribution is summarized as follows: (1) Stochastic
interpretation of Michaelis-Menten equation is given. (2) Notion of
\textit{probability flow} is introduced in relation to detailed balance. (3) A
stochastic analogy of \textit{Wegscheider condition} is given in relation to
loops in the state transition diagram. (4) A simple graphical method of
computing the regulatory activity in terms of ligands' concentrations is
obtained for Wegscheider cases.Comment: 20 pages, 13 figure
Visualizing RAD51-mediated joint molecules: implications for recombination mechanism and the effect of sequence heterology
The defining event in homologous recombination is the exchange of base-paired partners between a single-stranded (ss) DNA and a homologous duplex driven by recombinase proteins, such as human RAD51. To understand the mechanism of this essential genome maintenance event, we analyzed the structure of RAD51–DNA complexes representing strand exchange intermediates at nanometer resolution by scanning force microscopy. Joint molecules were formed between substrates with a defined ssDNA segment and homologous region on a double-stranded (ds) partner. We discovered and quantified several notable architectural features of RAD51 joint molecules. Each end of the RAD51-bound joints had a distinct structure. Using linear substrates, a 10-nt region of mispaired bases blocked extension of joint molecules in all examples observed, whereas 4 nt of heterology only partially blocked joint molecule extension. Joint molecules, including 10 nt of heterology, had paired DNA on either side of the heterologous substitution, indicating that pairing could initiate from the free 3′end of ssDNA or from a region adjacent to the ss–ds junction. RAD51 filaments covering joint ss–dsDNA regions were more stable to disassembly than filaments covering dsDNA. We discuss how distinct structural features of RAD51-bound DNA joints can play important roles as recognition sites for proteins that facilitate and control strand exchange
Structure of the hDmc1-ssDNA filament reveals the principles of its architecture
In eukaryotes, meiotic recombination is a major source of genetic diversity, but its defects in humans lead to abnormalities such as Down's, Klinefelter's and other syndromes. Human Dmc1 (hDmc1), a RecA/Rad51 homologue, is a recombinase that plays a crucial role in faithful chromosome segregation during meiosis. The initial step of homologous recombination occurs when hDmc1 forms a filament on single-stranded (ss) DNA. However the structure of this presynaptic complex filament for hDmc1 remains unknown. To compare hDmc1-ssDNA complexes to those known for the RecA/Rad51 family we have obtained electron microscopy (EM) structures of hDmc1-ssDNA nucleoprotein filaments using single particle approach. The EM maps were analysed by docking crystal structures of Dmc1, Rad51, RadA, RecA and DNA. To fully characterise hDmc1-DNA complexes we have analysed their organisation in the presence of Ca2+, Mg2+, ATP, AMP-PNP, ssDNA and dsDNA. The 3D EM structures of the hDmc1-ssDNA filaments allowed us to elucidate the principles of their internal architecture. Similar to the RecA/Rad51 family, hDmc1 forms helical filaments on ssDNA in two states: extended (active) and compressed (inactive). However, in contrast to the RecA/Rad51 family, and the recently reported structure of hDmc1-double stranded (ds) DNA nucleoprotein filaments, the extended (active) state of the hDmc1 filament formed on ssDNA has nine protomers per helical turn, instead of the conventional six, resulting in one protomer covering two nucleotides instead of three. The control reconstruction of the hDmc1-dsDNA filament revealed 6.4 protein subunits per helical turn indicating that the filament organisation varies depending on the DNA templates. Our structural analysis has also revealed that the N-terminal domain of hDmc1 accomplishes its important role in complex formation through domain swapping between adjacent protomers, thus providing a mechanistic basis for coordinated action of hDmc1 protomers during meiotic recombination
Stochastic Inflation Revisited: Non-Slow Roll Statistics and DBI Inflation
Stochastic inflation describes the global structure of the inflationary
universe by modeling the super-Hubble dynamics as a system of matter fields
coupled to gravity where the sub-Hubble field fluctuations induce a stochastic
force into the equations of motion. The super-Hubble dynamics are ultralocal,
allowing us to neglect spatial derivatives and treat each Hubble patch as a
separate universe. This provides a natural framework in which to discuss
probabilities on the space of solutions and initial conditions. In this article
we derive an evolution equation for this probability for an arbitrary class of
matter systems, including DBI and k-inflationary models, and discover
equilibrium solutions that satisfy detailed balance. Our results are more
general than those derived assuming slow roll or a quasi-de Sitter geometry,
and so are directly applicable to models that do not satisfy the usual slow
roll conditions. We discuss in general terms the conditions for eternal
inflation to set in, and we give explicit numerical solutions of highly
stochastic, quasi-stationary trajectories in the relativistic DBI regime.
Finally, we show that the probability for stochastic/thermal tunneling can be
significantly enhanced relative to the Hawking-Moss instanton result due to
relativistic DBI effects.Comment: 38 pages, 2 figures. v3: minor revisions; version accepted into JCA
Brane Inflation and Cosmic String Tension in Superstring Theory
In a simple reanalysis of the KKLMMT scenario, we argue that the slow roll
condition in the D3-anti-D3-brane inflationary scenario in superstring theory
requires no more than a moderate tuning. The cosmic string tension is very
sensitive to the conformal coupling: with less fine-tuning, the cosmic string
tension (as well as the ratio of tensor to scalar perturbation mode) increases
rapidly and can easily saturate the present observational bound. In a
multi-throat brane inflationary scenario, this feature substantially improves
the chance of detecting and measuring the properties of the cosmic strings as a
window to the superstring theory and our pre-inflationary universe.Comment: Combined bounds from WMAP and SDSS Lyman alpha experiments are added
for analysis, changes are added to the tabl
A Note on Noncommutative Brane Inflation
In this paper, we investigate the noncommutative KKLMMT D3/anti-D3 brane
inflation scenario in detail. Incorporation of the brane inflation scenario and
the noncommutative inflation scenario can nicely explain the large negative
running of the spectral index as indicated by WMAP three-year data and can
significantly release the fine-tuning for the parameter . Using the WMAP
three year results (blue-tilted spectral index with large negative running), we
explore the parameter space and give the constraints and predictions for the
inflationary parameters and cosmological observables in this scenario. We show
that this scenario predicts a quite large tensor/scalar ratio and what is more,
a too large cosmic string tension (assuming that the string coupling is
in its likely range from 0.1 to 1) to be compatible with the present
observational bound. A more detailed analysis reveals that this model has some
inconsistencies according to the fit to WMAP three year results.Comment: 20 pages, 5 figures; accepted for publication in JCA
The Use of High-Solids Loadings in Biomass Pretreatment – A Review
The use of high‐solids loadings (≥ 15% solids, w/w) in the unit operations of lignocellulose conversion processes potentially offers many advantages over lower‐solids loadings, including increased sugar and ethanol concentrations and decreased production and capital costs. Since the term lignocellulosic materials refers to a wide range of feedstocks (agricultural and forestry residues, distillery by‐products, and dedicated energy crops like grasses), the term “solids loading” here is defined by the amount of dry material that enters the process divided by the total mass of material and water added to the material. The goal of this study is to provide a consolidated review of studies using a high‐solids pretreatment step in the conversion process. Included in this review is a brief discussion of the limitations, such as the lack of available water to promote mass transfer, increased substrate viscosity, and increased concentration of inhibitors produced affecting pretreatment, as well as descriptions and findings of pretreatment studies performed at high solids, the latest reactor designs developed for pretreatment at bench‐ and pilot‐scales to address some of the limitations, and high‐solids pretreatment operations that have been scaled‐up and incorporated into demonstration facilities
Inter-subunit interactions that coordinate Rad51's activities
Rad51 is the central catalyst of homologous recombination in eukaryotes and is thus critical for maintaining genomic integrity. Recent crystal structures of filaments formed by Rad51 and the closely related archeal RadA and eubacterial RecA proteins place the ATPase site at the protomeric interface. To test the relevance of this feature, we mutated conserved residues at this interface and examined their effects on key activities of Rad51: ssDNA-stimulated ATP hydrolysis, DNA binding, polymerization on DNA substrates and catalysis of strand-exchange reactions. Our results show that the interface seen in the crystal structures is very important for nucleoprotein filament formation. H352 and R357 of yeast Rad51 are essential for assembling the catalytically competent form of the enzyme on DNA substrates and coordinating its activities. However, contrary to some previous suggestions, neither of these residues is critical for ATP hydrolysis
Evolutionary Analysis of Mitogenomes from Parasitic and Free-Living Flatworms
Copyright: © 2015 Solà et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The attached file is the published version of the article
A denitrifying community associated with a major, marine nitrogen fixer
The diazotrophic cyanobacterium, Trichodesmium, is an integral component of the marine nitrogen cycle and contributes significant amounts of new nitrogen to oligotrophic, tropical/subtropical ocean surface waters. Trichodesmium forms macroscopic, fusiform (tufts), spherical (puffs) and raft-like colonies that provide a pseudobenthic habitat for a host of other organisms including marine invertebrates, microeukaryotes and numerous other microbes. The diversity and activity of denitrifying bacteria found in association with the colonies was interrogated using a series of molecular-based methodologies targeting the gene encoding the terminal step in the denitrification pathway, nitrous oxide reductase (nosZ). Trichodesmium spp. sampled from geographically isolated ocean provinces (the Atlantic Ocean, the Red Sea and the Indian Ocean) were shown to harbor highly similar, taxonomically related communities of denitrifiers whose members are affiliated with the Roseobacter clade within the Rhodobacteraceae (Alphaproteobacteria). These organisms were actively expressing nosZ in samples taken from the mid-Atlantic Ocean and Red Sea implying that Trichodesmium colonies are potential sites of nitrous oxide consumption and perhaps earlier steps in the denitrification pathway also. It is proposed that coupled nitrification of newly fixed N is the most likely source of nitrogen oxides supporting nitrous oxide cycling within Trichodesmium colonies
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