Steady-state stabilization due to random delays in maps with self-feedback loops and in globally delayed-coupled maps

We study the stability of the fixed-point solution of an array of mutually coupled logistic maps, focusing on the influence of the delay times, $\tau_{ij}$, of the interaction between the $i$th and $j$th maps. Two of us recently reported [Phys. Rev. Lett. {\bf 94}, 134102 (2005)] that if $\tau_{ij}$ are random enough the array synchronizes in a spatially homogeneous steady state. Here we study this behavior by comparing the dynamics of a map of an array of $N$ delayed-coupled maps with the dynamics of a map with $N$ self-feedback delayed loops. If $N$ is sufficiently large, the dynamics of a map of the array is similar to the dynamics of a map with self-feedback loops with the same delay times. Several delayed loops stabilize the fixed point, when the delays are not the same; however, the distribution of delays plays a key role: if the delays are all odd a periodic orbit (and not the fixed point) is stabilized. We present a linear stability analysis and apply some mathematical theorems that explain the numerical results.Comment: 14 pages, 13 figures, important changes (title changed, discussion, figures, and references added

Trapping and Characterization of a Reaction Intermediate in Carbapenem Hydrolysis by \u3cem\u3eB. cereus\u3c/em\u3e Metallo-β-lactamase

Metallo-β-lactamases hydrolyze most β-lactam antibiotics. The lack of a successful inhibitor for them is related to the previous failure to characterize a reaction intermediate with a clinically useful substrate. Stopped-flow experiments together with rapid freeze−quench EPR and Raman spectroscopies were used to characterize the reaction of Co(II)−BcII with imipenem. These studies show that Co(II)−BcII is able to hydrolyze imipenem in both the mono- and dinuclear forms. In contrast to the situation met for penicillin, the species that accumulates during turnover is an enzyme−intermediate adduct in which the β-lactam bond has already been cleaved. This intermediate is a metal-bound anionic species with a novel resonant structure that is stabilized by the metal ion at the DCH or Zn2 site. This species has been characterized based on its spectroscopic features. This represents a novel, previously unforeseen intermediate that is related to the chemical nature of carbapenems, as confirmed by the finding of a similar intermediate for meropenem. Since carbapenems are the only substrates cleaved by B1, B2, and B3 lactamases, identification of this intermediate could be exploited as a first step toward the design of transition-state-based inhibitors for all three classes of metallo-β-lactamases

Molecular Techniques for Dicistrovirus Detection without RNA Extraction or Purification

Dicistroviridae is a new family of small, nonenveloped, and +ssRNA viruses pathogenic to both beneficial arthropods and insect pests as well. Triatoma virus (TrV), a dicistrovirus, is a pathogen of Triatoma infestans (Hemiptera: Reduviidae), one of the main vectors of Chagas disease. In this work, we report a single-step method to identify TrV, a dicistrovirus, isolated from fecal samples of triatomines. The identification method proved to be quite sensitive, even without the extraction and purification of RNA virus.Centro de Estudios Parasitológicos y de Vectore

Descripción geoquímica y geocronológica de secuencias volcánicas neogenas de Trasarco, en el extremo oriental de la Cadena Volcánica Transversal del Quevar (Noroeste de Argentina)

Se realizaron 34 nuevas dataciones K/Ar y 39 análisis geoquímicos de elementos mayoritarios, trazas y tierras raras, que implican n u evas aportaciones sobre las secuencias volcánicas neógenas de trasarco pertenecientes a la cadena volcánica transversal del Queva r. Esta cadena volcánica parte del arco volcánico actual con dirección W N W-ESE hasta las cercanías de la localidad de San Antonio de los Cobres. Se han reconocido y estudiado centros volcánicos ubicados en el extremo oriental de la misma. Los diferentes pulsos detectados en cada uno de estos centros (Aguas Calientes, Acay, El Morro-Organullo y Tocomar) son geoquímica y petrogr á ficamente homogéneos. Se interpreta que las cámaras magmáticas involucradas no han estado estratificadas composicionalmente ni han tenido sectores enriquecidos en cristales. Como excepción, el centro eru p t ivo A c ay muestra un rango composicional desde términos andesíticos a riolíticos. En este caso, se interpreta un fraccionamiento de la cámara magmática en pulsos de edad similar. La composición isotópica del centro eruptivo Aguas Calientes indica una fuerte componente cortical en la formación de los magmas. Es posible explicar su origen a partir de fusión cortical. Las determinaciones geocronológicas realizadas muestran pulsos volcánicos a los 17-19 Ma, 13-12 Ma, 10 Ma, 7-6 Ma, 1-0.5 Ma en esta región de los Andes Centrales

Solvents to Fragments to Drugs: MD Applications in Drug Design

Simulations of molecular dynamics (MD) are playing an increasingly important role in structure-based drug discovery (SBDD). Here we review the use of MD for proteins in aqueous solvation, organic/aqueous mixed solvents (MDmix) and with small ligands, to the classic SBDD problems: Binding mode and binding free energy predictions. The simulation of proteins in their condensed state reveals solvent structures and preferential interaction sites (hot spots) on the protein surface. The information provided by water and its cosolvents can be used very effectively to understand protein ligand recognition and to improve the predictive capability of well-established methods such as molecular docking. The application of MD simulations to the study of the association of proteins with drug-like compounds is currently only possible for specific cases, as it remains computationally very expensive and labor intensive. MDmix simulations on the other hand, can be used systematically to address some of the common tasks in SBDD. With the advent of new tools and faster computers we expect to see an increase in the application of mixed solvent MD simulations to a plethora of protein targets to identify new drug candidates

Virion Structure and In Vitro Genome Release Mechanism of Dicistrovirus Kashmir Bee Virus

Infections with Kashmir bee virus (KBV) are lethal for honeybees and have been associated with colony collapse disorder. KBV and closely related viruses contribute to the ongoing decline in the number of honeybee colonies in North America, Europe, Australia, and other parts of the world. Despite the economic and ecological impact of KBV, its structure and infection process remain unknown. Here, we present the structure of the virion of KBV determined to a resolution of 2.8 angstrom. We show that the exposure of KBV to acidic pH induces a reduction in interpentamer contacts within capsids and the reorganization of its RNA genome from a uniform distribution to regions of high and low density. Capsids of KBV crack into pieces at acidic pH, resulting in the formation of open particles lacking pentamers of capsid proteins. The large openings of capsids enable the rapid release of genomes and thus limit the probability of their degradation by RNases. The opening of capsids may be a shared mechanism for the genome release of viruses from the family Dicistroviridae. IMPORTANCE The western honeybee (Apis mellifera) is indispensable for maintaining agricultural productivity as well as the abundance and diversity of wild flowering plants. However, bees suffer from environmental pollution, parasites, and pathogens, including viruses. Outbreaks of virus infections cause the deaths of individual honeybees as well as collapses of whole colonies. Kashmir bee virus has been associated with colony collapse disorder in the United States, and no cure for the disease is currently available. Here, we report the structure of an infectious particle of Kashmir bee virus and show how its protein capsid opens to release the genome. Our structural characterization of the infection process determined that therapeutic compounds stabilizing contacts between pentamers of capsid proteins could prevent the genome release of the virus.We gratefully acknowledge the Cryoelectron Microscopy and Tomography core facility of CEITEC supported by MEYS CR (LM2018127) . This research was carried out under the project CEITEC 2020 (LQ1601) , with financial support from the MEYS of the Czech Republic under National Sustainability Program II. This work was supported by IT4I project (CZ.1.05/1.1.00/02.0070) , funded by the European Regional Development Fund and the national budget of the Czech Republic via the RDIOP, as well as the MEYS via the grant (LM2011033) . The research of G.A.M. was supported by the grants CONICET (PIP 20150288) , 247 Agencia Nacional de Promocion Cientifica y Tecnica, Argentina (PICT no. 2015-248 0665, PICT No. 20181545) , and Universidad Nacional de La Plata, Argentina. The research of D.M.A.G. was supported by a Grupos Consolidados grant from the University of the Basque Country, Spain (GIU18/172) . The research leading to these results received funding from the Grant Agency of the Czech Republic grant GX19-25982X to P.P

Role of PheE15 gate in ligand entry and nitric oxide detoxification function of Mycobacterium tuberculosis truncated hemoglobin N

The truncated hemoglobin N, HbN, of Mycobacterium tuberculosis is endowed with a potent nitric oxide dioxygenase (NOD) activity that allows it to relieve nitrosative stress and enhance in vivo survival of its host. Despite its small size, the protein matrix of HbN hosts a two-branched tunnel, consisting of orthogonal short and long channels, that connects the heme active site to the protein surface. A novel dual-path mechanism has been suggested to drive migration of O(2) and NO to the distal heme cavity. While oxygen migrates mainly by the short path, a ligand-induced conformational change regulates opening of the long tunnel branch for NO, via a phenylalanine (PheE15) residue that acts as a gate. Site-directed mutagenesis and molecular simulations have been used to examine the gating role played by PheE15 in modulating the NOD function of HbN. Mutants carrying replacement of PheE15 with alanine, isoleucine, tyrosine and tryptophan have similar O(2)/CO association kinetics, but display significant reduction in their NOD function. Molecular simulations substantiated that mutation at the PheE15 gate confers significant changes in the long tunnel, and therefore may affect the migration of ligands. These results support the pivotal role of PheE15 gate in modulating the diffusion of NO via the long tunnel branch in the oxygenated protein, and hence the NOD function of HbN

Structure of the Triatoma virus capsid

The members of the Dicistroviridae family are non-enveloped positive-sense single-stranded RNA (+ssRNA) viruses pathogenic to beneficial arthropods as well as insect pests of medical importance. Triatoma virus (TrV), a member of this family, infects several species of triatomine insects (popularly named kissing bugs), which are vectors for human trypanosomiasis, more commonly known as Chagas disease. The potential use of dicistroviruses as biological control agents has drawn considerable attention in the past decade, and several viruses of this family have been identified, with their targets covering honey bees, aphids and field crickets, among others. Here, the crystal structure of the TrV capsid at 2.5 14;Å resolution is reported, showing that as expected it is very similar to that of Cricket paralysis virus (CrPV). Nevertheless, a number of distinguishing structural features support the introduction of a new genus (Triatovirus; type species TrV) under the Dicistroviridae family. The most striking differences are the absence of icosahedrally ordered VP4 within the infectious particle and the presence of prominent projections that surround the fivefold axis. Furthermore, the structure identifies a second putative autoproteolytic DDF motif in protein VP3, in addition to the conserved one in VP1 which is believed to be responsible for VP0 cleavage during capsid maturation. The potential meaning of these new findings is discussed.Centro de Estudios Parasitológicos y de Vectore

Dynamics of delayed-coupled chaotic logistic maps: influence of network topology, connectivity and delay times

We review our recent work on the synchronization of a network of delay-coupled maps, focusing on the interplay of the network topology and the delay times that take into account the finite velocity of propagation of interactions. We assume that the elements of the network are identical ($N$ logistic maps in the regime where the individual maps, without coupling, evolve in a chaotic orbit) and that the coupling strengths are uniform throughout the network. We show that if the delay times are sufficiently heterogeneous, for adequate coupling strength the network synchronizes in a spatially homogeneous steady-state, which is unstable for the individual maps without coupling. This synchronization behavior is referred to as ``suppression of chaos by random delays'' and is in contrast with the synchronization when all the interaction delay times are homogeneous, because with homogeneous delays the network synchronizes in a state where the elements display in-phase time-periodic or chaotic oscillations. We analyze the influence of the network topology considering four different types of networks: two regular (a ring-type and a ring-type with a central node) and two random (free-scale Barabasi-Albert and small-world Newman-Watts). We find that when the delay times are sufficiently heterogeneous the synchronization behavior is largely independent of the network topology but depends on the networks connectivity, i.e., on the average number of neighbors per node.Comment: 5 pages, 7 figures. Also submitted to Pramana: the journal of the Indian Academy of Sciences. To appear in the Proceedings of "Perspectives on Nonlinear Dynamics 2007

Molecular Techniques for Dicistrovirus Detection without RNA Extraction or Purification

Dicistroviridae is a new family of small, nonenveloped, and +ssRNA viruses pathogenic to both beneficial arthropods and insect pests as well. Triatoma virus (TrV), a dicistrovirus, is a pathogen of Triatoma infestans (Hemiptera: Reduviidae), one of the main vectors of Chagas disease. In this work, we report a single-step method to identify TrV, a dicistrovirus, isolated from fecal samples of triatomines. The identification method proved to be quite sensitive, even without the extraction and purification of RNA virus.Centro de Estudios Parasitológicos y de Vectore