Singularities in ternary mixtures of k-core percolation

Heterogeneous k-core percolation is an extension of a percolation model which has interesting applications to the resilience of networks under random damage. In this model, the notion of node robustness is local, instead of global as in uniform k-core percolation. One of the advantages of k-core percolation models is the validity of an analytical mathematical framework for a large class of network topologies. We study ternary mixtures of node types in random networks and show the presence of a new type of critical phenomenon. This scenario may have useful applications in the stability of large scale infrastructures and the description of glass-forming systems.Comment: To appear in Complex Networks, Studies in Computational Intelligence, Proceedings of CompleNet 201

Weak percolation on multiplex networks

peer-reviewedBootstrap percolation is a simple but nontrivial model. It has applications in many areas of science and has been explored on random networks for several decades. In single-layer (simplex) networks, it has been recently observed that bootstrap percolation, which is defined as an incremental process, can be seen as the opposite of pruning percolation, where nodes are removed according to a connectivity rule. Here we propose models of both bootstrap and pruning percolation for multiplex networks. We collectively refer to these two models with the concept of "weak" percolation, to distinguish them from the somewhat classical concept of ordinary ("strong") percolation. While the two models coincide in simplex networks, we show that they decouple when considering multiplexes, giving rise to a wealth of critical phenomena. Our bootstrap model constitutes the simplest example of a contagion process on a multiplex network and has potential applications in critical infrastructure recovery and information security. Moreover, we show that our pruning percolation model may provide a way to diagnose missing layers in a multiplex network. Finally, our analytical approach allows us to calculate critical behavior and characterize critical clusters.PUBLISHEDpeer-reviewe

Control of template positioning during de novo initiation of RNA synthesis by the bovine viral diarrhea virus NS5B polymerase

The RNA-dependent RNA polymerase of the hepatitis C virus and the bovine viral diarrhea virus (BVDV) is able to initiate RNA synthesis de novo in the absence of a primer. Previous crystallographic datahave pointed to the existence of a GTP-specific binding site (G-site) that is located in the vicinity of the active site of the BVDV enzyme. Here we have studied the functional role of the G-site and present evidence to show that specific GTP binding affects the positioning of the template during de novo initiation. Following the formation of the first phosphodiester bond, the polymerase translocates relative to the newly synthesized dinucleotide, which brings the 5′-end of the primer into the G-site, releasing the previously bound GTP. At this stage, the 3′-end of the template can remain opposite to the 5′-end of the primer or be repositioned to its original location before RNA synthesis proceeds. We show that the template can freely move between the two locations, and both complexes can isomerize to equilibrium. These data suggest that the bound GTP can stabilize the interaction between the 3′-end of the template and the priming nucleotide, preventing the template to overshoot and extend beyond the active site during de novo initiation. The hepatitis C virus enzyme utilizes a dinucleotide primer exclusively from the blunt end; the existence of a functionally equivalent G-site is therefore uncertain. For the BVDV polymerase we showed that de novo initiation is severely compromised by the T320A mutant that likely affects hydrogen bonding between the G-site and the guanine base. Dinucleotide-primed reactions are not influenced by this mutation, which supports the notion that the G-site is located in close proximity but not at the active site of the enzyme. © 2006 by The American Society for Biochemistry and Molecular Biology, Inc

The new low-toxic histone deacetylase inhibitor S-(2) induces apoptosis in various acute myeloid leukemia cells

Histone deacetylase inhibitors (HDACi) induce tumour cell cycle arrest and/or apoptosis, and some of them are currently used in cancer therapy. Recently, we described a series of powerful HDACi characterized by a 1,4-benzodiazepine (BDZ) ring hybridized with a linear alkyl chain bearing a hydroxamate function as Zn(++)-chelating group. Here, we explored the anti-leukaemic properties of three novel hybrids, namely the chiral compounds (S)-2 and (R)-2, and their non-chiral analogue 4, which were first comparatively tested in promyelocytic NB4 cells. (S)-2 and partially 4– but not (R)-2 – caused G0/G1 cell-cycle arrest by up-regulating cyclin G2 and p21 expression and down-regulating cyclin D2 expression, and also apoptosis as assessed by cell morphology and cytofluorimetric assay, histone H2AX phosphorylation and PARP cleavage. Notably, these events were partly prevented by an anti-oxidant. Moreover, novel HDACi prompted p53 and α-tubulin acetylation and, consistently, inhibited HDAC1 and 6 activity. The rank order of potency was (S)-2 > 4 > (R)-2, reflecting that of other biological assays and addressing (S)-2 as the most effective compound capable of triggering apoptosis in various acute myeloid leukaemia (AML) cell lines and blasts from patients with different AML subtypes. Importantly, (S)-2 was safe in mice (up to 150 mg/kg/week) as determined by liver, spleen, kidney and bone marrow histopathology; and displayed negligible affinity for peripheral/central BDZ-receptors. Overall, the BDZ-hydroxamate (S)-2 showed to be a low-toxic HDACi with powerful anti-proliferative and pro-apototic activities towards different cultured and primary AML cells, and therefore of clinical interest to support conventional anti-leukaemic therapy

Insights into the architecture and stoichiometry of Escherichia coli PepA•DNA complexes involved in transcriptional control and site-specific DNA recombination by atomic force microscopy

Multifunctional Aminopeptidase A (PepA) from Escherichia coli is involved in the control of two distinct DNA transaction processes: transcriptional repression of the carAB operon, encoding carbamoyl phosphate synthase and site-specific resolution of ColE1-type plasmid multimers. Both processes require communication at a distance along a DNA molecule and PepA is the major structural component of the nucleoprotein complexes that underlie this communication. Atomic Force Microscopy was used to analyze the architecture of PepA·carAB and PepA·cer site complexes. Contour length measurements, bending angle analyses and volume determinations demonstrate that the carP1 operator is foreshortened by ∼235 bp through wrapping around one PepA hexamer. The highly deformed part of the operator extends from slightly upstream of the –35 hexamer of the carP1 promoter to just downstream of the IHF-binding site, and comprises the binding sites for the PurR and RutR transcriptional regulators. This extreme remodeling of the carP1 control region provides a straightforward explanation for the strict requirement of PepA in the establishment of pyrimidine and purine-specific repression of carAB transcription. We further provide a direct physical proof that PepA is able to synapse two cer sites in direct repeat in a large interwrapped nucleoprotein complex, likely comprising two PepA hexamers

Atomistic model of diopside–K-jadeite (CaMgSi2O6–KAlSi2O6) solid solution

Atomistic model was proposed to describe the thermodynamics of mixing in the diopside–K-jadeite solid solution (CaMgSi2O6–KAlSi2O6). The simulations were based on minimization of the latticeenergies of 800 structures within a 2 × 2 × 4 supercell of C2/c diopside with the compositions betweenCaMgSi2O6 and KAlSi2O6 and with variable degrees of order/disorder in the arrangement of Ca/K cations in M2 site and Mg/Al in Ml site. The energy minimization was performed with the help of a force-field model. The results of the calculations were used to define a generalized Ising model, which included 37 pair interaction parameters. Isotherms of the enthalpy of mixing within the range of 273–2023 K were calculated with a Monte Carlo algorithm, while the Gibbs free energies of mixing were obtained by thermodynamic integration of the enthalpies of mixing. The calculated T–X diagram for the system CaMgSi2O6–KAlSi2O6 at temperatures below 1000 K shows several miscibility gaps, which are separated by intervals of stability of intermediate ordered compounds. At temperatures above 1000 K a homogeneous solid solution is formed. The standard thermodynamic properties of K-adeite (KAlSi2O6) evaluated from quantum mechanical calculations were used to determine location of several mineral reactions with the participation of the diopside–K-jadeite solid solution. The results of the simulations suggest that the low content of KalSi2O6 in natural clinopyroxenes is not related to crystal chemical factors preventing isomorphism, but is determined by relatively high standard enthalpy of this end member