Polymer-grafted multiwall carbon nanotubes functionalized by nitrene chemistry: effect on cooperativity and phase miscibility

The demixing of polystyrene (PS) and poly(vinyl methylether) (PVME) was systematically investigated in the presence of surface functionalized multiwall carbon nanotubes (MWNTs) by melt rheology. As PS-PVME blends are weakly interacting blends, the contribution of conformational entropy increases, resulting in thermo-rheological complexity wherein the concentration fluctuation persists even beyond the critical demixing temperature. These phenomenal changes were followed here in the presence of MWNTs with different surface functional groups. Polystyrene was synthesised by atom transfer radical polymerization and was immobilized onto carboxyl acid functionalized multiwall carbon nanotubes (COOH-MWNTs) via nitrene chemistry in order to improve the phase miscibility in PS-PVME blends. Interestingly, blends with 0.25 wt% polystyrene grafted multiwall carbon nanotubes (PS-g-MWNTs) delayed the spinodal decomposition temperature in the blends by similar to 33 degrees C with respect to both control blends and those with COOH-MWNTs. While the localization of COOH-MWNTs in PVME was explained from a thermodynamic point of view, the localization of PS-g-MWNTs was understood to result from favorable PS-PVME contact and the degree of surface coverage of PS on the surface of MWNTs. The length of the cooperative rearranging region (xi) decreased in presence of PS-g-MWNTs, suggesting confinement effects on large scale motions and enhanced interchain concentration fluctuation.

Universal power law in crossover from integrability to quantum chaos

We study models of interacting fermions in one dimension to investigate the crossover from integrability to nonintegrability, i.e., quantum chaos, as a function of system size. Using exact diagonalization of finite-sized systems, we study this crossover by obtaining the energy level statistics and Drude weight associated with transport. Our results reinforce the idea that for system size L -> infinity nonintegrability sets in for an arbitrarily small integrability-breaking perturbation. The crossover value of the perturbation scales as a power law similar to L-eta when the integrable system is gapless. The exponent eta approximate to 3 appears to be robust to microscopic details and the precise form of the perturbation. We conjecture that the exponent in the power law is characteristic of the random matrix ensemble describing the nonintegrable system. For systems with a gap, the crossover scaling appears to be faster than a power law.

Serum proteomics of hepatitis C virus infection reveals retinol-binding protein 4 as a novel regulator

Persistent infection of hepatitis C virus (HCV) can lead to liver cirrhosis and hepatocellular carcinoma, which are currently diagnosed by invasive liver biopsy. Approximately 15-20% of cases of chronic liver diseases in India are caused by HCV infection. In North India, genotype 3 is predominant, whereas genotype 1 is predominant in southern parts of India. The aim of this study was to identify differentially regulated serum proteins in HCV-infected Indian patients (genotypes 1 and 3) using a two-dimensional electrophoresis approach. We identified eight differentially expressed proteins by MS. Expression levels of one of the highly upregulated proteins, retinol-binding protein 4 (RBP4), was validated by ELISA and Western blotting in two independent cohorts. We also confirmed our observation in the JFH1 infectious cell culture system. Interestingly, the HCV core protein enhanced RBP4 levels and partial knockdown of RBP4 had a positive impact on HCV replication, suggesting a possible role for this cellular protein in regulating HCV infection. Analysis of RBP4-interacting partners using a bioinformatic approach revealed novel insights into the possible involvement of RBP4 in HCV-induced pathogenesis. Taken together, this study provided information on the proteome profile of the HCV-infected Indian population, and revealed a link between HCV infection, RBP4 and insulin resistance.

Mycobacterium tuberculosis Rho Is an NTPase with Distinct Kinetic Properties and a Novel RNA-Binding Subdomain

Two mechanisms - factor independent and dependent termination - ensure the completion of RNA synthesis in eubacteria. Factor-dependent mechanism relies on the Rho protein to terminate transcription by interacting with RNA polymerase. Although well studied in Escherichia coli, the properties of the Rho homologs from most bacteria are not known. The rho gene is unusually large in genus Mycobacterium and other members of actinobacteria, having,150 additional residues towards the amino terminal end. We describe the distinct properties of Rho from Mycobacterium tuberculosis. It is an NTPase with a preference for purine nucleoside triphosphates with kinetic properties different from E. coli homolog and an ability to use various RNA substrates. The N-terminal subdomain of MtbRho can bind to RNA by itself, and appears to contribute to the interaction of the termination factor with RNAs. Furthermore, the interaction with RNA induces changes in conformation and oligomerization of MtbRho.

Finite size scaling in crossover among different random matrix ensembles in microscopic lattice models

Using numerical diagonalization we study the crossover among different random matrix ensembles (Poissonian, Gaussian orthogonal ensemble (GOE), Gaussian unitary ensemble (GUE) and Gaussian symplectic ensemble (GSE)) realized in two different microscopic models. The specific diagnostic tool used to study the crossovers is the level spacing distribution. The first model is a one-dimensional lattice model of interacting hard-core bosons (or equivalently spin 1/2 objects) and the other a higher dimensional model of non-interacting particles with disorder and spin-orbit coupling. We find that the perturbation causing the crossover among the different ensembles scales to zero with system size as a power law with an exponent that depends on the ensembles between which the crossover takes place. This exponent is independent of microscopic details of the perturbation. We also find that the crossover from the Poissonian ensemble to the other three is dominated by the Poissonian to GOE crossover which introduces level repulsion while the crossover from GOE to GUE or GOE to GSE associated with symmetry breaking introduces a subdominant contribution. We also conjecture that the exponent is dependent on whether the system contains interactions among the elementary degrees of freedom or not and is independent of the dimensionality of the system.

Fine-tuning solid-state luminescence in NPIs (1,8-naphthalimides): impact of the molecular environment and cumulative interactions

An investigation of a series of seven angular ``V'' shaped NPIs (1-7) is presented. The effect of substitution of these structurally similar NPIs on their photophysical properties in the solution-state and the solid-state is presented and discussed in light of experimental and computational findings. Compounds 1-7 show negligible to intensely strong emission yields in their solid-state depending on the nature of substituents appended to the oxoaryl moiety. The solution and solid-state properties of the compounds can be directly correlated with their structural rigidity, nature of substituents and intermolecular interactions. The versatile solid-state structures of the NPI siblings are deeply affected by the pendant substituents. All of the NPIs (1-7) show antiparallel dimeric pi-pi stacking interactions in their solid-state which can further extend in a parallel, alternate, orthogonal or lateral fashion depending on the steric and electronic nature of the C-4' substituents. Structural investigations including Hirshfeld surface analysis methods reveal that where strongly interacting systems show weak to moderate emission in their condensed states, weakly interacting systems show strong emission yields under the same conditions. The nature of packing and extended structures also affects the emission colors of the NPIs in their solid-states. Furthermore, DFT computational studies were utilized to understand the molecular and cumulative electronic behaviors of the NPIs. The comprehensive studies provide insight into the condensed-state luminescence of aggregationprone small molecules like NPIs and help to correlate the structure-property relationships.

Iron(III) Catecholates for Cellular Imaging and Photocytotoxicity in Red Light

Iron(III) complexes Fe(L)(L') (NO3)]-in which L is phenyl-N, N-bis(pyridin-2-yl) methyl]methanamine (1), (anthracen-9-yl)N, N-bis(pyridin-2-yl) methyl] methanamine (2), (pyreny-1-yl)-N, N-bis(pyridin- 2-yl) methyl] methanamine (3-5), and L' is catecholate (1-3), 4-tert-butyl catecholate (4), and 4-(2-aminoethyl)benzene- 1,2-diolate (5)-were synthesized and their photocytotoxic proper-ties examined. The five electron-paramagnetic complexes displayed a FeIII/ Fe-II redox couple near similar to 0.4 V versus a saturated calomel electrode (SCE) in DMF/0.1m tetrabutylammonium perchlorate (TBAP). They showed unpre-cedented photocytotoxicity in red light (600-720 nm) to give IC50-15 mm in various cell lines by means of apoptosis to generate reactive oxygen species. They were ingested in the nucleus of HeLa and HaCaT cells in 4 h, thereby interacting favorably with calf thymus (ct)-DNA and photocleaving pUC19 DNA in red light of 785 nm to form hydroxyl radicals.

Flocking at a distance in active granular matter

The self-organized motion of vast numbers of creatures in a single direction is a spectacular example of emergent order. Here, we recreate this phenomenon using actuated nonliving components. We report here that millimetre-sized tapered rods, rendered motile by contact with an underlying vibrated surface and interacting through a medium of spherical beads, undergo a phase transition to a state of spontaneous alignment of velocities and orientations above a threshold bead area fraction. Guided by a detailed simulation model, we construct an analytical theory of this flocking transition, with two ingredients: a moving rod drags beads; neighbouring rods reorient in the resulting flow like a weathercock in the wind. Theory and experiment agree on the structure of our phase diagram in the plane of rod and bead concentrations and power-law spatial correlations near the phase boundary. Our discovery suggests possible new mechanisms for the collective transport of particulate or cellular matter.

Re-analysis of cryoEM data on HCV IRES bound to 40S subunit of human ribosome integrated with recent structural information suggests new contact regions between ribosomal proteins and HCV RNA

In this study, we combine available high resolution structural information on eukaryotic ribosomes with low resolution cryo-EM data on the Hepatitis C Viral RNA (IRES) human ribosome complex. Aided further by the prediction of RNA-protein interactions and restrained docking studies, we gain insights on their interaction at the residue level. We identified the components involved at the major and minor contact regions, and propose that there are energetically favorable local interactions between 40S ribosomal proteins and IRES domains. Domain II of the IRES interacts with ribosomal proteins S5 and S25 while the pseudoknot and the downstream domain IV region bind to ribosomal proteins S26, S28 and S5. We also provide support using UV cross-linking studies to validate our proposition of interaction between the S5 and IRES domains II and IV. We found that domain IIIe makes contact with the ribosomal protein S3a (S1e). Our model also suggests that the ribosomal protein S27 interacts with domain IIIc while S7 has a weak contact with a single base RNA bulge between junction IIIabc and IIId. The interacting residues are highly conserved among mammalian homologs while IRES RNA bases involved in contact do not show strict conservation. IRES RNA binding sites for S25 and S3a show the best conservation among related viral IRESs. The new contacts identified between ribosomal proteins and RNA are consistent with previous independent studies on RNA-binding properties of ribosomal proteins reported in literature, though information at the residue level is not available in previous studies.

Fluorine prefers hydrogen bonds over halogen bonds! Insights from crystal structures of some halofluorobenzenes

Crystal structures of a series of isomers of chlorofluorobenzene, bromofluorobenzene and iodofluorobenzene, all of which are liquids under ambient conditions, are determined by a technique of in situ cryocrystallography. These simple dihalo substituted benzenes provide clear insights into subtle interplay of packing interactions preferred by fluorine and heavier halogens for example, C-H center dot center dot center dot X hydrogen bonds vs. X center dot center dot center dot X halogen bonds (X=F, Cl, Br, I). The interaction patterns noted here are purely characteristic of halogens, having not been influenced by other stronger interactions. Variability of principal supramolecular synthons among the isomers highlights the importance of molecular shape and relative position of interacting atoms while preserving the basic intermolecular bonds. Mutually exclusive occurrence of homo (I center dot center dot center dot I) and hetero (I center dot center dot center dot F) halogen bonds in polymorphs of 4-iodofluorobenzene questions the robustness and reliability of these interactions.

Hydrophobic hydration driven self-assembly of curcumin in water: Similarities to nucleation and growth under large metastability, and an analysis of water dynamics at heterogeneous surfaces

As the beneficial effects of curcumin have often been reported to be limited to its small concentrations, we have undertaken a study to find the aggregation properties of curcumin in water by varying the number of monomers. Our molecular dynamics simulation results show that the equilibrated structure is always an aggregated state with remarkable structural rearrangements as we vary the number of curcumin monomers from 4 to 16 monomers. We find that the curcumin monomers form clusters in a very definite pattern where they tend to aggregate both in parallel and anti-parallel orientation of the phenyl rings, often seen in the formation of beta-sheet in proteins. A considerable enhancement in the population of parallel alignments is observed with increasing the system size from 12 to 16 curcumin monomers. Due to the prevalence of such parallel alignment for large system size, a more closely packed cluster is formed with maximum number of hydrophobic contacts. We also follow the pathway of cluster growth, in particular the transition from the initial segregated to the final aggregated state. We find the existence of a metastable structural intermediate involving a number of intermediate-sized clusters dispersed in the solution. We have constructed a free energy landscape of aggregation where the metatsable state has been identified. The course of aggregation bears similarity to nucleation and growth in highly metastable state. The final aggregated form remains stable with the total exclusion of water from its sequestered hydrophobic core. We also investigate water structure near the cluster surface along with their orientation. We find that water molecules form a distorted tetrahedral geometry in the 1st solvation layer of the cluster, interacting rather strongly with the hydrophilic groups at the surface of the curcumin. The dynamics of such quasi-bound water molecules near the surface of curcumin cluster is considerably slower than the bulk signifying a restricted motion as often found in protein hydration layer. (C) 2014 AIP Publishing LLC.

Collective eigenstates of emission in an N-entity heterostructure and the evaluation of its Green tensors and self-energy components

Optical emission from emitters strongly interacting among themselves and also with other polarizable matter in close proximity has been approximated by emission from independent emitters. This is primarily due to our inability to evaluate the self-energy matrices and radiative properties of the collective eigenstates of emitters in heterogeneous ensembles. A method to evaluate self-energy matrices that is not limited by the geometry and material composition is presented to understand and exploit such collective excitations. Numerical evaluations using this method are used to highlight the significant differences between independent and the collective modes of emission in nanoscale heterostructures. A set of N Lorentz emitters and other polarizable entities is used to represent the coupled system of a generalized geometry in a volume integral approach. Closed form relations between the Green tensors of entity pairs in free space and their correspondents in a heterostructure are derived concisely. This is made possible for general geometries because the global matrices consisting of all free-space Green dyads are subject to conservation laws. The self-energy matrix can then be assembled using the evaluated Green tensors of the heterostructure, but a decomposition of its components into their radiative and nonradiative decay contributions is nontrivial. The relations to compute the observables of the eigenstates (such as quantum efficiency, power/energy of emission, radiative and nonradiative decay rates) are presented. A note on extension of this method to collective excitations, which also includes strong interactions with a surface in the near-field, is added. (C) 2014 Optical Society of America

Interaction of Sesbania mosaic virus (SeMV) RNA-dependent RNA polymerase (RdRp) with the p10 domain of polyprotein 2a and its implications in SeMV replication

Identification of viral encoded proteins that interact with RNA-dependent RNA polymerase (RdRp) is an important step towards unraveling the mechanism of replication. Sesbania mosaic virus (SeMV) RdRp was shown to interact strongly with p10 domain of polyprotein 2a and moderately with the protease domain. Mutational analysis suggested that the C-terminal disordered domain of RdRp is involved in the interaction with p10. Coexpression of full length RdRp and p10 resulted in formation of RdRp-p10 complex which showed significantly higher polymerase activity than RdRp alone. Interestingly, C Delta 43 RdRp also showed a similar increase in activity. Thus, p10 acts as a positive regulator of RdRp by interacting with the C-terminal disordered domain of RdRp. (C) 2014 The Authors. Published by Elsevier B.V.

Chemical specificity and conformational flexibility in proteinase-inhibitor interaction: Scaffolds for promiscuous binding

One of the most important roles of proteins in cellular milieu is recognition of other biomolecules including other proteins. Protein protein complexes are involved in many essential cellular processes. Interfaces of protein protein complexes are traditionally known to be conserved in evolution and less flexible than other solvent interacting tertiary structural surface. But many examples are emerging where these features do not hold good. An understanding of inter-play between flexibility and sequence conservation is emerging, providing a fresh dimension to the paradigm of sequence structure function relationship. The functional manifestation of the inter-relation between sequence conservation and flexibility of interface is exemplified in this review using proteinase inhibitor protein complexes. (C) 2014 Elsevier Ltd. All rights reserved.

From Workstations to Workbenches: Towards Predicting Physicochemically Viable Protein-Protein Interactions Across a Host and a Pathogen

The understanding of protein-protein interactions is indispensable in comprehending most of the biological processes in a cell. Small-scale experiments as well as large-scale high-throughput techniques over the past few decades have facilitated identification and analysis of protein-protein interactions which form the basis of much of our knowledge on functional and regulatory aspects of proteins. However, such rich catalog of interaction data should be used with caution when establishing protein-protein interactions in silico, as the high-throughput datasets are prone to false positives. Numerous computational means developed to pursue genome-wide studies on protein-protein interactions at times overlook the mechanistic and molecular details, thus questioning the reliability of predicted protein-protein interactions. We review the development, advantages, and shortcomings of varied approaches and demonstrate that by providing a structural viewpoint in terms of shape complementarity and interaction energies at protein-protein interfaces coupled with information on expression and localization of proteins homologous to an interacting pair, it is possible to assess the credibility of predicted interactions in biological context. With a focus on human pathogen Mycobacterium tuberculosis H37Rv, we show that such scrupulous use of details at the molecular level can predict physicochemically viable protein-protein interactions across host and pathogen. Such predicted interactions have the potential to provide molecular basis of probable mechanisms of pathogenesis and hence open up ways to explore their usefulness as targets in the light of drug discovery. (c) 2014 IUBMB Life, 66(11):759-774, 2014