Elasticity and electrostatics of plectonemic DNA

We present a self-contained theory for the mechanical response of DNA in single molecule experiments. Our model is based on a 1D continuum description of the DNA molecule and accounts both for its elasticity and for DNA-DNA electrostatic interactions. We consider the classical loading geometry used in experiments where one end of the molecule is attached to a substrate and the other one is pulled by a tensile force and twisted by a given number of turns. We focus on configurations relevant to the limit of a large number of turns, which are made up of two phases, one with linear DNA and the other one with superhelical DNA. The model takes into account thermal fluctuations in the linear phase and electrostatic interactions in the superhelical phase. The values of the torsional stress, of the supercoiling radius and angle, and key features of the experimental extension-rotation curves, namely the slope of the linear region and thermal buckling threshold, are predicted. They are found in good agreement with experimental data.Comment: 19 pages and 6 figure

The EDELWEISS Experiment : Status and Outlook

The EDELWEISS Dark Matter search uses low-temperature Ge detectors with heat and ionisation read- out to identify nuclear recoils induced by elastic collisions with WIMPs from the galactic halo. Results from the operation of 70 g and 320 g Ge detectors in the low-background environment of the Modane Underground Laboratory (LSM) are presented.Comment: International Conference on Dark Matter in Astro and Particle Physics (Dark 2000), Heidelberg, Germany, 10-16 Jul 2000, v3 minor revision

Dark Matter Search in the Edelweiss Experiment

Preliminary results obtained with 320g bolometers with simultaneous ionization and heat measurements are described. After a few weeks of data taking, data accumulated with one of these detectors are beginning to exclude the upper part of the DAMA region. Prospects for the present run and the second stage of the experiment, EDELWEISS-II, using an innovative reversed cryostat allowing data taking with 100 detectors, are briefly described.Comment: IDM 2000, 3rd International Workshop on the Identification of Dark Matter, York (GB), 18-22/09/2000, v2.0 minor modification

Event categories in the EDELWEISS WIMP search experiment

Four categories of events have been identified in the EDELWEISS-I dark matter experiment using germanium cryogenic detectors measuring simultaneously charge and heat signals. These categories of events are interpreted as electron and nuclear interactions occurring in the volume of the detector, and electron and nuclear interactions occurring close to the surface of the detectors(10-20 mu-m of the surface). We discuss the hypothesis that low energy surface nuclear recoils,which seem to have been unnoticed by previous WIMP searches, may provide an interpretation of the anomalous events recorded by the UKDMC and Saclay NaI experiments. The present analysis points to the necessity of taking into account surface nuclear and electron recoil interactions for a reliable estimate of background rejection factors.Comment: 11 pages, submitted to Phys. Lett.

First Results of the EDELWEISS WIMP Search using a 320 g Heat-and-Ionization Ge Detector

The EDELWEISS collaboration has performed a direct search for WIMP dark matter using a 320 g heat-and-ionization cryogenic Ge detector operated in a low-background environment in the Laboratoire Souterrain de Modane. No nuclear recoils are observed in the fiducial volume in the 30-200 keV energy range during an effective exposure of 4.53 kg.days. Limits for the cross-section for the spin-independent interaction of WIMPs and nucleons are set in the framework of the Minimal Supersymmetric Standard Model (MSSM). The central value of the signal reported by the experiment DAMA is excluded at 90% CL.Comment: 14 pages, Latex, 4 figures. Submitted to Phys. Lett.

DNA cruciform arms nucleate through a correlated but non-synchronous cooperative mechanism

Inverted repeat (IR) sequences in DNA can form non-canonical cruciform structures to relieve torsional stress. We use Monte Carlo simulations of a recently developed coarse-grained model of DNA to demonstrate that the nucleation of a cruciform can proceed through a cooperative mechanism. Firstly, a twist-induced denaturation bubble must diffuse so that its midpoint is near the centre of symmetry of the IR sequence. Secondly, bubble fluctuations must be large enough to allow one of the arms to form a small number of hairpin bonds. Once the first arm is partially formed, the second arm can rapidly grow to a similar size. Because bubbles can twist back on themselves, they need considerably fewer bases to resolve torsional stress than the final cruciform state does. The initially stabilised cruciform therefore continues to grow, which typically proceeds synchronously, reminiscent of the S-type mechanism of cruciform formation. By using umbrella sampling techniques we calculate, for different temperatures and superhelical densities, the free energy as a function of the number of bonds in each cruciform along the correlated but non-synchronous nucleation pathways we observed in direct simulations.Comment: 12 pages main paper + 11 pages supplementary dat

Helical Chirality: a Link between Local Interactions and Global Topology in DNA

DNA supercoiling plays a major role in many cellular functions. The global DNA conformation is however intimately linked to local DNA-DNA interactions influencing both the physical properties and the biological functions of the supercoiled molecule. Juxtaposition of DNA double helices in ubiquitous crossover arrangements participates in multiple functions such as recombination, gene regulation and DNA packaging. However, little is currently known about how the structure and stability of direct DNA-DNA interactions influence the topological state of DNA. Here, a crystallographic analysis shows that due to the intrinsic helical chirality of DNA, crossovers of opposite handedness exhibit markedly different geometries. While right-handed crossovers are self-fitted by sequence-specific groove-backbone interaction and bridging Mg2+ sites, left-handed crossovers are juxtaposed by groove-groove interaction. Our previous calculations have shown that the different geometries result in differential stabilisation in solution, in the presence of divalent cations. The present study reveals that the various topological states of the cell are associated with different inter-segmental interactions. While the unstable left-handed crossovers are exclusively formed in negatively supercoiled DNA, stable right-handed crossovers constitute the local signature of an unusual topological state in the cell, such as the positively supercoiled or relaxed DNA. These findings not only provide a simple mechanism for locally sensing the DNA topology but also lead to the prediction that, due to their different tertiary intra-molecular interactions, supercoiled molecules of opposite signs must display markedly different physical properties. Sticky inter-segmental interactions in positively supercoiled or relaxed DNA are expected to greatly slow down the slithering dynamics of DNA. We therefore suggest that the intrinsic helical chirality of DNA may have oriented the early evolutionary choices for DNA topology

Transdimensional inversion of receiver functions and surface wave dispersion

International audienceWe present a novel method for joint inversion of receiver functions and surface wave dispersion data, using a transdimensional Bayesian formulation. This class of algorithm treats the number of model parameters (e.g. number of layers) as an unknown in the problem. The dimension of the model space is variable and a Markov chain Monte Carlo (McMC) scheme is used to provide a parsimonious solution that fully quantifies the degree of knowledge one has about seismic structure (i.e constraints on the model, resolution, and trade-offs). The level of data noise (i.e. the covariance matrix of data errors) effectively controls the information recoverable from the data and here it naturally determines the complexity of the model (i.e. the number of model parameters). However, it is often difficult to quantify the data noise appropriately, particularly in the case of seismic waveform inversion where data errors are correlated. Here we address the issue of noise estimation using an extended Hierarchical Bayesian formulation, which allows both the variance and covariance of data noise to be treated as unknowns in the inversion. In this way it is possible to let the data infer the appropriate level of data fit. In the context of joint inversions, assessment of uncertainty for different data types becomes crucial in the evaluation of the misfit function. We show that the Hierarchical Bayes procedure is a powerful tool in this situation, because it is able to evaluate the level of information brought by different data types in the misfit, thus removing the arbitrary choice of weighting factors. After illustrating the method with synthetic tests, a real data application is shown where teleseismic receiver functions and ambient noise surface wave dispersion measurements from the WOMBAT array (South-East Australia) are jointly inverted to provide a probabilistic 1D model of shear-wave velocity beneath a given station

Oscillatory stimuli differentiate adapting circuit topologies

This is the author accepted manuscript. The final version is available from Springer Nature via the DOI in this record.Biology emerges from interactions between molecules, which are challenging to elucidate with current techniques. An orthogonal approach is to probe for 'response signatures' that identify specific circuit motifs. For example, bistability, hysteresis, or irreversibility are used to detect positive feedback loops. For adapting systems, such signatures are not known. Only two circuit motifs generate adaptation: negative feedback loops (NFLs) and incoherent feed-forward loops (IFFLs). On the basis of computational testing and mathematical proofs, we propose differential signatures: in response to oscillatory stimulation, NFLs but not IFFLs show refractory-period stabilization (robustness to changes in stimulus duration) or period skipping. Applying this approach to yeast, we identified the circuit dominating cell cycle timing. In Caenorhabditis elegans AWA neurons, which are crucial for chemotaxis, we uncovered a Ca2+ NFL leading to adaptation that would be difficult to find by other means. These response signatures allow direct access to the outlines of the wiring diagrams of adapting systems.The work was supported by US National Institutes of Health grant 5RO1-GM078153-07 (F.R.C.), NRSA Training Grant CA009673-36A1 (S.J.R.), a Merck Postdoctoral Fellowship at The Rockefeller University (S.J.R.), and the Simons Foundation (S.J.R.). J.L. was supported by a fellowship from the Boehringer Ingelheim Fonds. E.D.S. was partially supported by the US Office of Naval Research (ONR N00014-13-1-0074) and the US Air Force Office of Scientific Research (AFOSR FA9550-14-1-0060)

Oscillatory Dynamics of Cell Cycle Proteins in Single Yeast Cells Analyzed by Imaging Cytometry

Progression through the cell division cycle is orchestrated by a complex network of interacting genes and proteins. Some of these proteins are known to fluctuate periodically during the cell cycle, but a systematic study of the fluctuations of a broad sample of cell-cycle proteins has not been made until now. Using time-lapse fluorescence microscopy, we profiled 16 strains of budding yeast, each containing GFP fused to a single gene involved in cell cycle regulation. The dynamics of protein abundance and localization were characterized by extracting the amplitude, period, and other indicators from a series of images. Oscillations of protein abundance could clearly be identified for Cdc15, Clb2, Cln1, Cln2, Mcm1, Net1, Sic1, and Whi5. The period of oscillation of the fluorescently tagged proteins is generally in good agreement with the inter-bud time. The very strong oscillations of Net1 and Mcm1 expression are remarkable since little is known about the temporal expression of these genes. By collecting data from large samples of single cells, we quantified some aspects of cell-to-cell variability due presumably to intrinsic and extrinsic noise affecting the cell cycle