199 research outputs found
Force-induced misfolding in RNA
RNA folding is a kinetic process governed by the competition of a large
number of structures stabilized by the transient formation of base pairs that
may induce complex folding pathways and the formation of misfolded structures.
Despite of its importance in modern biophysics, the current understanding of
RNA folding kinetics is limited by the complex interplay between the weak
base-pair interactions that stabilize the native structure and the disordering
effect of thermal forces. The possibility of mechanically pulling individual
molecules offers a new perspective to understand the folding of nucleic acids.
Here we investigate the folding and misfolding mechanism in RNA secondary
structures pulled by mechanical forces. We introduce a model based on the
identification of the minimal set of structures that reproduce the patterns of
force-extension curves obtained in single molecule experiments. The model
requires only two fitting parameters: the attempt frequency at the level of
individual base pairs and a parameter associated to a free energy correction
that accounts for the configurational entropy of an exponentially large number
of neglected secondary structures. We apply the model to interpret results
recently obtained in pulling experiments in the three-helix junction S15 RNA
molecule (RNAS15). We show that RNAS15 undergoes force-induced misfolding where
force favors the formation of a stable non-native hairpin. The model reproduces
the pattern of unfolding and refolding force-extension curves, the distribution
of breakage forces and the misfolding probability obtained in the experiments.Comment: 28 pages, 11 figure
Dissemination of antibiotic resistance genes associated with the sporobiota in sediments impacted by wastewater.
Aquatic ecosystems serve as a dissemination pathway and a reservoir of both antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARG). In this study, we investigate the role of the bacterial sporobiota to act as a vector for ARG dispersal in aquatic ecosystems. The sporobiota was operationally defined as the resilient fraction of the bacterial community withstanding a harsh extraction treatment eliminating the easily lysed fraction of the total bacterial community. The sporobiota has been identified as a critical component of the human microbiome, and therefore potentially a key element in the dissemination of ARG in human-impacted environments. A region of Lake Geneva in which the accumulation of ARG in the sediments has been previously linked to the deposition of treated wastewater was selected to investigate the dissemination of <i>tet</i> (W) and <i>sul</i> 1, two genes conferring resistance to tetracycline and sulfonamide, respectively. Analysis of the abundance of these ARG within the sporobiome (collection of genes of the sporobiota) and correlation with community composition and environmental parameters demonstrated that ARG can spread across the environment with the sporobiota being the dispersal vector. A highly abundant OTU affiliated with the genus <i>Clostridium</i> was identified as a potential specific vector for the dissemination of <i>tet</i> (W), due to a strong correlation with <i>tet</i> (W) frequency (ARG copy numbers/ng DNA). The high dispersal rate, long-term survival, and potential reactivation of the sporobiota constitute a serious concern in terms of dissemination and persistence of ARG in the environment
Trap models with slowly decorrelating observables
We study the correlation and response dynamics of trap models of glassy
dynamics, considering observables that only partially decorrelate with every
jump. This is inspired by recent work on a microscopic realization of such
models, which found strikingly simple linear out-of-equilibrium
fluctuation-dissipation relations in the limit of slow decorrelation. For the
Barrat-Mezard model with its entropic barriers we obtain exact results at zero
temperature for arbitrary decorrelation factor . These are then
extended to nonzero , where the qualitative scaling behaviour and all
scaling exponents can still be found analytically. Unexpectedly, the choice of
transition rates (Glauber versus Metropolis) affects not just prefactors but
also some exponents. In the limit of slow decorrelation even complete scaling
functions are accessible in closed form. The results show that slowly
decorrelating observables detect persistently slow out-of-equilibrium dynamics,
as opposed to intermittent behaviour punctuated by excursions into fast,
effectively equilibrated states.Comment: 29 pages, IOP styl
Tailoring symmetry groups using external alternate fields
Macroscopic systems with continuous symmetries subjected to oscillatory
fields have phases and transitions that are qualitatively different from their
equilibrium ones. Depending on the amplitude and frequency of the fields
applied, Heisenberg ferromagnets can become XY or Ising-like -or, conversely,
anisotropies can be compensated -thus changing the nature of the ordered phase
and the topology of defects. The phenomena can be viewed as a dynamic form of
"order by disorder".Comment: 4 pages, 2 figures finite dimension and selection mechanism clarifie
Exploiting the fungal highway: development of a novel tool for the in situ isolation of bacteria migrating along fungal mycelium
Fungi and bacteria form various associations that are central to numerous environmental processes. In the so-called fungal highway, bacteria disperse along fungal mycelium. We developed a novel tool for the in situ isolation of bacteria moving along fungal hyphae as well as for the recovery of fungi potentially involved in dispersal, both of which are attracted towards a target culture medium. We present the validation and the results of the first in situ test. Couples of fungi and bacteria were isolated from soil. Amongst the enriched organisms, we identified several species of fast-growing fungi (Fusarium sp. and Chaetomium sp.), as well as various potentially associated bacterial groups, including Variovorax soli, Olivibacter soli, Acinetobacter calcoaceticus, and several species of the genera Stenotrophomonas, Achromobacter and Ochrobactrum. Migration of bacteria along fungal hyphae across a discontinuous medium was confirmed in most of the cases. Although the majority of the bacteria for which migration was confirmed were also positive for flagellar motility, not all motile bacteria dispersed using their potential fungal partner. In addition, the importance of hydrophobicity of the fungal mycelial surface was confirmed. Future applications of the columns include targeting different types of microorganisms and their interactions, either by enrichment or by state of the art molecular biological method
Number partitioning as random energy model
Number partitioning is a classical problem from combinatorial optimisation.
In physical terms it corresponds to a long range anti-ferromagnetic Ising spin
glass. It has been rigorously proven that the low lying energies of number
partitioning behave like uncorrelated random variables. We claim that
neighbouring energy levels are uncorrelated almost everywhere on the energy
axis, and that energetically adjacent configurations are uncorrelated, too.
Apparently there is no relation between geometry (configuration) and energy
that could be exploited by an optimization algorithm. This ``local random
energy'' picture of number partitioning is corroborated by numerical
simulations and heuristic arguments.Comment: 8+2 pages, 9 figures, PDF onl
Dynamical transition for a particle in a squared Gaussian potential
We study the problem of a Brownian particle diffusing in finite dimensions in
a potential given by where is Gaussian random field.
Exact results for the diffusion constant in the high temperature phase are
given in one and two dimensions and it is shown to vanish in a power-law
fashion at the dynamical transition temperature. Our results are confronted
with numerical simulations where the Gaussian field is constructed, in a
standard way, as a sum over random Fourier modes. We show that when the number
of Fourier modes is finite the low temperature diffusion constant becomes
non-zero and has an Arrhenius form. Thus we have a simple model with a fully
understood finite size scaling theory for the dynamical transition. In addition
we analyse the nature of the anomalous diffusion in the low temperature regime
and show that the anomalous exponent agrees with that predicted by a trap
model.Comment: 18 pages, 4 figures .eps, JPA styl
Experimental free energy measurements of kinetic molecular states using fluctuation theorems
Recent advances in non-equilibrium statistical mechanics and single molecule
technologies make it possible to extract free energy differences from
irreversible work measurements in pulling experiments. To date, free energy
recovery has been focused on native or equilibrium molecular states, whereas
free energy measurements of kinetic states (i.e. finite lifetime states that
are generated dynamically and are metastable) have remained unexplored. Kinetic
states can play an important role in various domains of physics, such as
nanotechnology or condensed matter physics. In biophysics, there are many
examples where they determine the fate of molecular reactions: protein and
peptide-nucleic acid binding, specific cation binding, antigen-antibody
interactions, transient states in enzymatic reactions or the formation of
transient intermediates and non-native structures in molecular folders. Here we
demonstrate that it is possible to obtain free energies of kinetic states by
applying extended fluctuation relations. This is shown by using optical
tweezers to mechanically unfold and refold DNA structures exhibiting
intermediate and misfolded kinetic states.Comment: main paper (16 pages, 5 figures) and supplementary information (22
pages, 14 figures
A dynamical model reveals gene co-localizations in nucleus
Co-localization of networks of genes in the nucleus is thought to play an important role in determining gene expression patterns. Based upon experimental data, we built a dynamical model to test whether pure diffusion could account for the observed co-localization of genes within a defined subnuclear region. A simple standard Brownian motion model in two and three dimensions shows that preferential co-localization is possible for co-regulated genes without any direct interaction, and suggests the occurrence may be due to a limitation in the number of available transcription factors. Experimental data of chromatin movements demonstrates that fractional rather than standard Brownian motion is more appropriate to model gene mobilizations, and we tested our dynamical model against recent static experimental data, using a sub-diffusion process by which the genes tend to colocalize more easily. Moreover, in order to compare our model with recently obtained experimental data, we studied the association level between genes and factors, and presented data supporting the validation of this dynamic model. As further applications of our model, we applied it to test against more biological observations. We found that increasing transcription factor number, rather than factory number and nucleus size, might be the reason for decreasing gene co-localization. In the scenario of frequency-or amplitude-modulation of transcription factors, our model predicted that frequency-modulation may increase the co-localization between its targeted genes
- …