Effect of genome sequence on the force-induced unzipping of a DNA molecule

We considered a dsDNA polymer in which distribution of bases are random at the base pair level but ordered at a length of 18 base pairs and calculated its force elongation behaviour in the constant extension ensemble. The unzipping force $F(y)$ vs. extension $y$ is found to have a series of maxima and minima. By changing base pairs at selected places in the molecule we calculated the change in $F(y)$ curve and found that the change in the value of force is of the order of few pN and the range of the effect depending on the temperature, can spread over several base pairs. We have also discussed briefly how to calculate in the constant force ensemble a pause or a jump in the extension-time curve from the knowledge of $F(y)$

Discrete elastic model for stretching-induced flagellar polymorphs

Force-induced reversible transformations between coiled and normal polymorphs of bacterial flagella have been observed in recent optical-tweezer experiment. We introduce a discrete elastic rod model with two competing helical states governed by a fluctuating spin-like variable that represents the underlying conformational states of flagellin monomers. Using hybrid Brownian dynamics Monte-Carlo simulations, we show that a helix undergoes shape transitions dominated by domain wall nucleation and motion in response to externally applied uniaxial tension. A scaling argument for the critical force is presented in good agreement with experimental and simulation results. Stretching rate-dependent elasticity including a buckling instability are found, also consistent with the experiment

Brane Bremsstrahlung in DBI Inflation

We consider the effect of trapped branes on the evolution of a test brane whose motion generates DBI inflation along a warped throat. The coupling between the inflationary brane and a trapped brane leads to the radiation of non-thermal particles on the trapped brane. We calculate the Gaussian spectrum of the radiated particles and their backreaction on the DBI motion of the inflationary brane. Radiation occurs for momenta lower than the speed of the test brane when crossing the trapped brane. The slowing down effect is either due to a parametric resonance when the interaction time is small compared to the Hubble time or a tachyonic resonance when the interaction time is large. In both cases the motion of the inflationary brane after the interaction is governed by a chameleonic potential,which tends to slow it down. We find that a single trapped brane can hardly slow down a DBI inflaton whose fluctuations lead to the Cosmic Microwave Background spectrum. A more drastic effect is obtained when the DBI brane encounters a tightly spaced stack of trapped branes.Comment: 20 pages, 1 figur

Syntectonic mobility of supergene nickel ores of New Caledonia (Southwest Pacific). Evidence from faulted regolith and garnierite veins.

International audienceSupergene nickel deposits of New Caledonia that have been formed in the Neogene by weathering of obducted ultramafic rocks are tightly controlled by fracture development. The relationship of tropical weathering and tectonic structures, faults and tension gashes, have been investigated in order to determine whether fractures have play a passive role only, as previously thought; or alternatively, if brittle tectonics was acting together with alteration. From the observation of time-relationship, textures, and mineralogy of various fracture fills and fault gouges, it may be unambiguously established that active faulting has play a prominent role not only in facilitating drainage and providing room for synkinematic crystallisation of supergene nickel silicate, but also in mobilising already formed sparse nickel ore, giving birth to the very high grade ore nicknamed "green gold"

Theory of High-Force DNA Stretching and Overstretching

Single molecule experiments on single- and double stranded DNA have sparked a renewed interest in the force-extension of polymers. The extensible Freely Jointed Chain (FJC) model is frequently invoked to explain the observed behavior of single-stranded DNA. We demonstrate that this model does not satisfactorily describe recent high-force stretching data. We instead propose a model (the Discrete Persistent Chain, or ``DPC'') that borrows features from both the FJC and the Wormlike Chain, and show that it resembles the data more closely. We find that most of the high-force behavior previously attributed to stretch elasticity is really a feature of the corrected entropic elasticity; the true stretch compliance of single-stranded DNA is several times smaller than that found by previous authors. Next we elaborate our model to allow coexistence of two conformational states of DNA, each with its own stretch and bend elastic constants. Our model is computationally simple, and gives an excellent fit through the entire overstretching transition of nicked, double-stranded DNA. The fit gives the first values for the elastic constants of the stretched state. In particular we find the effective bend stiffness for DNA in this state to be about 10 nm*kbt, a value quite different from either B-form or single-stranded DNAComment: 33 pages, 11 figures. High-quality figures available upon reques

Pairwise stimulations of pathogen-sensing pathways predict immune responses to multi-adjuvant combinations

The immune system makes decisions in response to combinations of multiple microbial inputs. We do not understand the combinatorial logic governing how higher-order combinations of microbial signals shape immune responses. Here, using coculture experiments and statistical analyses, we discover a general property for the combinatorial sensing of microbial signals, whereby the effects of triplet combinations of microbial signals on immune responses can be predicted by combining the effects of single and pairs. Mechanistically, we find that singles and pairs dictate the information signaled by triplets in mouse and human DCs at the levels of transcription, chromatin, and protein secretion. We exploit this simplifying property to develop cell-based immunotherapies prepared with adjuvant combinations that trigger protective responses in mouse models of cancer. We conclude that the processing of multiple input signals by innate immune cells is governed by pairwise effects, which will inform the rationale combination of adjuvants to manipulate immunity

Modeling a bacterial ecosystem through chemotaxis simulation of a single cell

International audienceWe present in this paper an artificial life ecosystem in which bacteria are evolved to perform chemotaxis. In this system, surviving bacteria have to overcome the problems of detecting resources (or sensing the environment), modulating their motion to generate a foraging behavior, and communicating with their kin to produce more sophisticated behaviors. A cell’s chemotactic pathway is modulated by a hybrid approach that uses an algebraic model for the receptor clusters activity, an ordinary differential equation for the adaptation dynamics, and a metabolic model that converts nutrients into biomass. The results show some analysis of the motion obtained from some bacteria and their effects on the evolved population behavior. The evolutionary process improves the bacteria’s ability to react to their environment, enhancing their growth and allowing them to better survive. As future work, we propose to investigate the effect of emergent bacterial communication as new species arise, and to explore the dynamics of colonies

Modeling DNA Structure, Elasticity and Deformations at the Base-pair Level

We present a generic model for DNA at the base-pair level. We use a variant of the Gay-Berne potential to represent the stacking energy between neighboring base-pairs. The sugar-phosphate backbones are taken into account by semi-rigid harmonic springs with a non-zero spring length. The competition of these two interactions and the introduction of a simple geometrical constraint leads to a stacked right-handed B-DNA-like conformation. The mapping of the presented model to the Marko-Siggia and the Stack-of-Plates model enables us to optimize the free model parameters so as to reproduce the experimentally known observables such as persistence lengths, mean and mean squared base-pair step parameters. For the optimized model parameters we measured the critical force where the transition from B- to S-DNA occurs to be approximately $140{pN}$. We observe an overstretched S-DNA conformation with highly inclined bases that partially preserves the stacking of successive base-pairs.Comment: 15 pages, 25 figures. submitted to PR

Single-molecule studies of the stringency factors and rates governing the polymerization of RecA on double-stranded DNA

RecA is a key protein in homologous recombination. During recombination, one single-stranded DNA (ssDNA) bound to site I in RecA exchanges Watson–Crick pairing with a sequence-matched ssDNA that was part of a double-stranded DNA molecule (dsDNA) bound to site II in RecA. After strand exchange, heteroduplex dsDNA is bound to site I. In vivo, direct polymerization of RecA on dsDNA through site I does not occur, though it does in vitro. The mechanisms underlying the difference have been unclear. We use single-molecule experiments to decouple the two steps involved in polymerization: nucleation and elongation. We find that elongation is governed by a fundamental clock that is insensitive to force and RecA concentration from 0.2 and 6 µM, though rates depend on ionic conditions. Thus, we can probe nucleation site stability by creating nucleation sites at high force and then measuring elongation as a function of applied force. We find that in the presence of ATP hydrolysis a minimum force is required for polymerization. The minimum force decreases with increasing RecA or ATP concentrations. We propose that force reduces the off-rate for nucleation site binding and that nucleation site stability is the stringency factor that prevents in vivo polymerization