High-Affinity Quasi-Specific Sites in the Genome: How the DNA-Binding Proteins Cope with Them

AbstractMany prokaryotic transcription factors home in on one or a few target sites in the presence of a huge number of nonspecific sites. Our analysis of λ-repressor in the Escherichia coli genome based on single basepair substitution experiments shows the presence of hundreds of sites having binding energy within 3 Kcal/mole of the OR1 binding energy, and thousands of sites with binding energy above the nonspecific binding energy. The effect of such sites on DNA-based processes has not been fully explored. The presence of such sites dramatically lowers the occupation probability of the specific site far more than if the genome were composed of nonspecific sites only. Our Brownian dynamics studies show that the presence of quasi-specific sites results in very significant kinetic effects as well. In contrast to λ-repressor, the E. coli genome has orders of magnitude lower quasi-specific sites for GalR, an integral transcription factor, thus causing little competition for the specific site. We propose that GalR and perhaps repressors of the same family have evolved binding modes that lead to much smaller numbers of quasi-specific sites to remove the untoward effects of genomic DNA

Scalable Anytime Algorithms for Learning Fragments

International audienceAbstract Linear temporal logic (LTL) is a specification language for finite sequences (called traces) widely used in program verification, motion planning in robotics, process mining, and many other areas. We consider the problem of learning formulas in fragments of LTL without the $$\mathbf {U}$$ U -operator for classifying traces; despite a growing interest of the research community, existing solutions suffer from two limitations: they do not scale beyond small formulas, and they may exhaust computational resources without returning any result. We introduce a new algorithm addressing both issues: our algorithm is able to construct formulas an order of magnitude larger than previous methods, and it is anytime, meaning that it in most cases successfully outputs a formula, albeit possibly not of minimal size. We evaluate the performances of our algorithm using an open source implementation against publicly available benchmarks

Flavour equilibration in quark-gluon plasma

Within the framework of a dynamical and physically transparent model developed earlier, we study the time evolution of various quark flavours in the baryon-free region in ultrarelativistic heavy ion collisions. We show that even under optimistic conditions, the quark-gluon system fails to achieve chemical equilibrium

Effect of osmolytes and chaperone-like action of p-protein on folding of nucleocapsid protein of Chandipura virus

Amino acid sequences of nucleocapsid proteins are mostly conserved among different rhabdoviruses. The protein plays a common functional role in different RNA viruses by enwrapping the viral genomic RNA in an RNase-resistant form. Upon expression of the nucleocapsid protein alone in COS cells and in bacteria, it forms large insoluble aggregates. In this work, we have reported for the first time the full-length cloning of the N gene of Chandipura virus and its expression in Escherichia coli in a soluble monomeric form and purification using nonionic detergents. The biological activity of the soluble recombinant protein has been tested, and it was found to possess efficient RNA-binding ability. The state of aggregation of the recombinant protein was monitored using light scattering. In the absence of nonionic detergents, it formed large aggregates. Aggregation was significantly reduced in the presence of osmolytes such asd-sorbitol. Aggregate formation was suppressed in the presence of another viral product, phosphoprotein P, in a chaperone-like manner. Both the osmolyte and phosphoprotein P also suppressed aggregation to a great extent during refolding from a guanidine hydrochloride-denatured form. The function of the phosphoprotein and osmolyte appears to be synergistic to keep the N-protein in a soluble biologically competent form in virus-infected cells