Effect of coordinated ions on structure and flexibility of parallel G-quadruplexes: A molecular dynamics study

ingle tract guanine residues can associate to form stable parallel quadruplex structures in the presence of certain cations. Nanosecond scale molecular dynamics simulations have been performed on fully solvated fibre model of parallel d(G(7)) quadruplex structures with Na+ or K+ ions coordinated in the cavity formed by the O6 atoms of the guanine bases. The AMBER 4.1 force field and Particle Mesh Ewald technique for electrostatic interactions have been used in all simulations. There quadruplex structures are stable during the simulation, with the middle four base tetrads showing root mean square deviation values between 0.5 to 0.8 Angstrom from the initial structure as well the high resolution crystal structure. Even in the absence of any coordinated ion in the initial structure, the G-quadruplex structure remains intact throughout the simulation. During the 1.1 ns MD simulation, one Nai counter ion from the solvent as well as several water molecules enter the central cavity to occupy the empty coordination sites within the parallel quadruplex and help stabilize the structure. Hydrogen bonding pattern depends on the nature of the coordinated ion, with the G-tetrad undergoing local structural variation to accommodate cations of different sizes. in the absence of any coordinated ion. due to strong mutual repulsion, O6 atoms within G-tetrad are forced farther apart from each other, which leads to a considerably different hydrogen bonding scheme within the G-tetrads and very favourable interaction energy between the guanine bases constituting a G-tetrad. However, a coordinated ion between G-tetrads provides extra stacking energy for the G-tetrads and makes the quadruplex structure more rigid. Na+ ions, within the quadruplex cavity, are more mobile than coordinated K+ ions. A number of hydrogen bonded water molecules are observed within the grooves of all quadruplex structures.

Reactions of coordinated bivalent tetradentate schiff-base chelates of nickel (II) and palladium (II)

Reactions of N,N′-n-propylene-bis(acetylacetoneimino) metal (II), M[n-P-(AI)2], where M=Ni(II) or Pd(II), with nitrosating reagents have been investigated. Mono- and di-nitrosated complexes were obtained selectively, depending upon the concentration of the nitrosating reagents and the reaction time. In both the cases, the γ-CH group is transformed to an ambidentate isonitroso group (>C=NOH), which coordinates to the metal ion by dislodging the already coordinated carbonyl group. The factors influencing the mode of binding of the isonitroso group have been discussed. The bromination reactions of the mono-nitrosated products of M[n-P-(AI)2] and Pd (II) complexes, Pd [E/i-P-(AI)2], where E/i-P-(AI)2 is a dianion of ethylene/i-propylene-bis (acetylacetoneimine), are also reported. The reaction products have been characterized by elemental analyses, electrical conductivity molecular weight determination, and ir, pmr and electronic spectral data.

Organometallic derivatives of diphosphazanes. 2. Seven-coordinated Group 6 metal tricarbonyl complexes of diphosphazane ligands. X-ray crystal structure of [WI2(CO)3{P(OPh)2}2NPh]

The reactions of the complexes [MI2(CO)3-(NCMe)2] (M = Mo, W) with the diphosphazane ligands RN{P(OPh)2}2 (R = Me, Ph) in CH2Cl2 at room temperature afford new seven-coordinated complexes of the type [MI2(CO)3{P(OPh)2}2NR]. The molybdenum complexes are sensitive to air oxidation even in the solid state, whereas the tungsten complexes are more stable in the solid state and in solution. The structure of the tungsten complex [WI2(CO)3{P(OPh)2}2NPh] has been determined by single-crystal X-ray diffraction. It crystallizes in the orthorhombic system with the space group Pna 2(1), a = 19.372 (2) angstrom, b = 11.511 (1) angstrom, c = 15.581 (1) angstrom, and Z = 4. Full-matrix least-squares refinement with 3548 reflections (I > 2.5-sigma-(I)) led to final R and R(w) values of 0.036 and 0.034, respectively. The complex adopts a slightly distorted pentagonal-bypyramidal geometry rarely observed for such a type of complexes; two phosphorus atoms of the diphosphazane ligand, two iodine atoms, and a carbonyl group occupy the equatorial plane, and the other two carbonyl groups, the apical positions.

A nanosecond molecular dynamics study of antiparallel d(G)(7) quadruplex structures: Effect of the coordinated cations

Nanosecond scale molecular dynamics simulations have been performed on antiparallel Greek key type d(G(7)) quadruplex structures with different coordinated ions, namely Na+ and K+ ion, water and Na+ counter ions, using the AMBER force field and Particle Mesh Ewald technique for electrostatic interactions. Antiparallel structures are stable during the simulation, with root mean square deviation values of similar to1.5 Angstrom from the initial structures. Hydrogen bonding patterns within the G-tetrads depend on the nature of the coordinated ion, with the G-tetrad undergoing local structural variation to accommodate different cations. However, alternating syn-anti arrangement of bases along a chain as well as in a quartet is maintained through out the MD simulation. Coordinated Na+ ions, within the quadruplex cavity are quite mobile within the central channel and can even enter or exit from the quadruplex core, whereas coordinated K+ ions are quite immobile. MD studies at 400 K indicate that K+ ion cannot come out from the quadruplex core without breaking the terminal G-tetrads. Smaller grooves in antiparallel structures are better binding sites for hydrated counter ions, while a string of hydrogen bonded water molecules are observed within both the small and large grooves. The hydration free energy for the K+ ion coordinated structure is more favourable than that for the Na+ ion coordinated antiparallel quadruplex structure.

Effect of coordinated ions on structure and flexiblity of parallel G-quandruplexes: a molecular dynamics study

Single tract guanine residues can associate to form stable parallel quadruplex structures in the presence of certain cations. Nanosecond scale molecular dynamics simulations have been performed on fully solvated fibre model of parallel d(G7) quadruplex structures with Na+ or K+ ions coordinated in the cavity formed by the 06 atoms of the guanine bases. The AMBER 4.1 force field and Particle Mesh Ewald technique for electrostatic interactions have been used in all simulations. These quadruplex structures are stable during the simulation, with the middle four base tetrads showing root mean square deviation values between 0.5 to 0.8 A from the initial structure as well the high resolution crystal structure. Even in the absence of any coordinated ion in the initial structure, the G-quadruplex structure remains intact throughout the simulation. During the 1.1 ns MD simulation, one Na+ counter ion from the solvent as well as several water molecules enter the central cavity to occupy the empty coordination sites within the parallel quadruplex and help stabilize the structure. Hydrogen bonding pattern depends on the nature of the coordinated ion, with the G-tetrad undergoing local structural variation to accommodate cations of different sizes. In the absence of any coordinated ion, due to strong mutual repulsion, 06 atoms within G-tetrad are forced farther apart from each other, which leads to a considerably different hydrogen bonding scheme within the G-tetrads and very favourable interaction energy between the guanine bases constituting a G-tetrad. However, a coordinated ion between G-tetrads provides extra stacking energy for the G-tetrads and makes the quadruplex structure more rigid. Na+ ions, within the quadruplex cavity, are more mobile than coordinated K+ ions. A number of hydrogen bonded water molecules are observed within the grooves of all quadruplex structures

Worker piping triggers hissing for coordinated colony defence in the dwarf honeybee Apis florea

Defending a large social insect colony containing several thousands of workers requires the simultaneous action of many individuals. Ideally this action involves communication between the workers, enabling coordinated action and a fast response. The Asian dwarf honeybee, Apis florea, is a small honeybee with an open nesting habit and a comparatively small colony size, features that leave them particularly exposed to predators. We describe here a novel defence response of these bees in which the emission of an initial warning signal from one individual (“piping”) is followed 0.3 to 0.7 seconds later by a general response from a large number of bees (“hissing”). Piping is audible to the human ear, with a fundamental frequency of 384 ± 31Hz and lasting for 0.82 ± 0.35 seconds. Hissing is a broad band, noisy signal, clearly audible to the human observer and produced by slight but visible movements of the bees' wings. Hissing begins in individuals close to the piping bee, spreads rapidly to neighbours and results in an impressive coordinated crescendo occasionally involving the entire colony. Piping and hissing are accompanied by a marked decrease, or even cessation, of worker activities such as forager dancing and departures from the colony. We show that whereas hissing of the colony can be elicited without piping, the sequential and correlated piping and hissing response is specific to the presence of potential predators close to the colony. We suggest that the combined audio-visual effect of the hissing might deter small predators, while the cessation of flight activity could decrease the risk of predation by birds and insects which prey selectively on flying bees.

String-like propagation of the 5-coordinated defect state in supercooled water: molecular origin of dynamic and thermodynamic anomalies

We find that at low temperature water, large amplitude (similar to 60 degrees) rotational jumps propagate like a string, with the length of propagation increasing with lowering temperature. The strings are formed by mobile 5-coordinated water molecules which move like a Glarum defect (J. Chem. Phys., 1960, 33, 1371), causing water molecules on the path to change from 4-coordinated to 5-coordinated and again back to 4-coordinated water, and in the process cause the tagged water molecule to jump, by following essentially the Laage-Hynes mechanism (Science, 2006, 311, 832-835). The effects on relaxation of the propagating defect causing large amplitude jumps are manifested most dramatically in the mean square displacement (MSD) and also in the rotational time correlation function of the O-H bond of the molecule that is visited by the defect (transient transition to the 5-coordinated state). The MSD and the decay of rotational time correlation function, both remain quenched in the absence of any visit by the defect, as postulated by Glarum long time ago. We establish a direct connection between these propagating events and the known thermodynamic and dynamic anomalies in supercooled water. These strings are found largely in the regions that surround the relatively rigid domains of 4-coordinated water molecules. The propagating strings give rise to a noticeable dynamical heterogeneity, quantified here by a sharp rise in the peak of the four-point density response function, chi(4)(t). This dynamics heterogeneity is also responsible for the breakdown of the Stokes-Einstein relation.

ESAT-6 induced COX-2 expression involves coordinated interplay between PI3K and MAPK signaling

Macrophages, as sentinels of robust host immunity, are key regulators of innate immune responses against invading mycobacteria; however, pathogenic mycobacteria survive in the infected host by subverting host innate immunity. Infection dependent expression of early secreted antigenic target protein 6 (ESAT-6) by Mycobacterium tuberculosis is strongly correlated with subversion of innate immune responses against invading mycobacteria. As a part of multifaceted immunity to mycobacterial infection, induced expression of cyclooxygenase-2 (COX-2) may act as an important influencing factor towards effective host immunity. In the current investigation, we demonstrate that ESAT-6 triggers COX-2 expression both in vitro and in vivo in a TLR2 dependent manner. Signaling perturbation data suggest that signaling dynamics of PI3K and p38 and JNK1/2 MAPK assume critical importance in ESAT-6 triggered expression of COX-2 in macrophages. Interestingly, ESAT-6 triggered PI3K-MAPK signaling axis holds the capacity to regulate coordinated activation of NF-kappa B and AP-1. Overall, current investigation provides mechanistic insights into ESAT-6 induced COX-2 expression and unravels TLR2 mediated interplay of PI3K and MAPK signaling axis as a rate-determining step during intricate host immune responses. These findings would serve as a paradigm to understand pathogenesis of mycobacterial infection and clearly pave a way towards development of novel therapeutics. (C) 2011 Elsevier Ltd. All rights reserved.

A Coordinated Interdependent Protein Circuitry Stabilizes the Kinetochore Ensemble to Protect CENP-A in the Human Pathogenic Yeast Candida albicans

Unlike most eukaryotes, a kinetochore is fully assembled early in the cell cycle in budding yeasts Saccharomyces cerevisiae and Candida albicans. These kinetochores are clustered together throughout the cell cycle. Kinetochore assembly on point centromeres of S. cerevisiae is considered to be a step-wise process that initiates with binding of inner kinetochore proteins on specific centromere DNA sequence motifs. In contrast, kinetochore formation in C. albicans, that carries regional centromeres of 3-5 kb long, has been shown to be a sequence independent but an epigenetically regulated event. In this study, we investigated the process of kinetochore assembly/disassembly in C. albicans. Localization dependence of various kinetochore proteins studied by confocal microscopy and chromatin immunoprecipitation (ChIP) assays revealed that assembly of a kinetochore is a highly coordinated and interdependent event. Partial depletion of an essential kinetochore protein affects integrity of the kinetochore cluster. Further protein depletion results in complete collapse of the kinetochore architecture. In addition, GFP-tagged kinetochore proteins confirmed similar time-dependent disintegration upon gradual depletion of an outer kinetochore protein (Dam1). The loss of integrity of a kinetochore formed on centromeric chromatin was demonstrated by reduced binding of CENP-A and CENP-C at the centromeres. Most strikingly, Western blot analysis revealed that gradual depletion of any of these essential kinetochore proteins results in concomitant reduction in cellular protein levels of CENP-A. We further demonstrated that centromere bound CENP-A is protected from the proteosomal mediated degradation. Based on these results, we propose that a coordinated interdependent circuitry of several evolutionarily conserved essential kinetochore proteins ensures integrity of a kinetochore formed on the foundation of CENP-A containing centromeric chromatin.

Predatory Fish Select for Coordinated Collective Motion in Virtual Prey

Movement in animal groups is highly varied and ranges from seemingly disordered motion in swarms to coordinated aligned motion in flocks and schools. These social interactions are often thought to reduce risk from predators, despite a lack of direct evidence. We investigated risk-related selection for collective motion by allowing real predators ( bluegill sunfish) to hunt mobile virtual prey. By fusing simulated and real animal behavior, we isolated predator effects while controlling for confounding factors. Prey with a tendency to be attracted toward, and to align direction of travel with, near neighbors tended to form mobile coordinated groups and were rarely attacked. These results demonstrate that collective motion could evolve as a response to predation, without prey being able to detect and respond to predators.

Rice LHS1/OsMADS1 Controls Floret Meristem Specification by Coordinated Regulation of Transcription Factors and Hormone Signaling Pathways

SEPALLATA (SEP) MADS box transcription factors mediate floral development in association with other regulators. Mutants in five rice (Oryza sativa) SEP genes suggest both redundant and unique functions in panicle branching and floret development. LEAFY HULL STERILE1/OsMADS1, from a grass-specific subgroup of LOFSEP genes, is required for specifying a single floret on the spikelet meristem and for floret organ development, but its downstream mechanisms are unknown. Here, key pathways and directly modulated targets of OsMADS1 were deduced from expression analysis after its knockdown and induction in developing florets and by studying its chromatin occupancy at downstream genes. The negative regulation of OsMADS34, another LOFSEP gene, and activation of OsMADS55, a SHORT VEGETATIVE PHASE-like floret meristem identity gene, show its role in facilitating the spikelet-to-floret meristem transition. Direct regulation of other transcription factor genes like OsHB4 (a class III homeodomain Leu zipper member), OsBLH1 (a BEL1-like homeodomain member), OsKANADI2, OsKANADI4, and OsETTIN2 show its role in meristem maintenance, determinacy, and lateral organ development. We found that the OsMADS1 targets OsETTIN1 and OsETTIN2 redundantly ensure carpel differentiation. The multiple effects of OsMADS1 in promoting auxin transport, signaling, and auxin-dependent expression and its direct repression of three cytokinin A-type response regulators show its role in balancing meristem growth, lateral organ differentiation, and determinacy. Overall, we show that OsMADS1 integrates transcriptional and signaling pathways to promote rice floret specification and development.

A three-component protocol for the enantiodifferentiation of amines using triphenyl borate and BINOL: is it an ion pair or an amine-coordinated complex?

The structure of the borate complex responsible for the enantiodifferentiation of amines using a previously reported three-component protocol has been established. The choice between an ion pair and an amine-coordinated complex with the N atom of the amine coordinated to the B atom is favored for the former structure based on the DFT-calculated B-11 NMR chemical shifts. In contrast to expectations, the anisotropies of the quadrupolar B-11 nucleus for the two structures were calculated to be indistinguishable with regard to their effect on the linewidth of the NMR signal. (C) 2014 Elsevier Ltd. All rights reserved.

Models and algorithms for detection and tracking of coordinated groups

In this paper, we describe models and algorithms for detection and tracking of group and individual targets. We develop two novel group dynamical models, within a continuous time setting, that aim to mimic behavioural properties of groups. We also describe two possible ways of modeling interactions between closely using Markov Random Field (MRF) and repulsive forces. These can be combined together with a group structure transition model to create realistic evolving group models. We use a Markov Chain Monte Carlo (MCMC)-Particles Algorithm to perform sequential inference. Computer simulations demonstrate the ability of the algorithm to detect and track targets within groups, as well as infer the correct group structure over time. ©2008 IEEE.