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Shiv Nadar University

(SoNS) School of Natural Sciences

The entry of the dengue virus is mediated by the conformational change in the envelope protein due to change in the endosomal pH. The structural study reveals that domain-III of the dengue envelope protein (DENV) shows the largest shift in its position during the entry of the virus. Therefore, targeting the hinge region of the domain-III may block the conformational changes in the DENV. In the present work, we have targeted the domain I/III hinge region using four known ligands used for the dengue envelope protein (serotype-2) and have intended to explore the specificity of one ligand R1 (5-(3-chlorophenyl)-N-(2-phenyl-2H-benzo[d][1,2,3]triazol-6-yl)furan-2-carboxamide) that succeeded the dengue inhibition by the molecular dynamics (MD) simulations in conjunction of the molecular docking and the binding free energy calculations. The residue interactions map shows Lys 296 of domain-III of the DENV-2, which might be responsible for binding small molecules between domain I/III interface, as an important residue conserved in all the dengue serotypes. © 2017, Springer-Verlag Berlin Heidelberg.

Chemistry

World University root node

Journal of Molecular Modeling

Targeting domain-III hinging of dengue envelope (DENV-2) protein by MD simulations, docking and free energy calculations

We report a discrete variant of Farkas’ Lemma in the setting of a module over a linearly ordered commutative ring. The ring may contain zero divisors, and need not be associative nor unital, but we need a certain hypothesis about the ring. Finally, we discuss the result and compare it with other related results found in the literature. © 2017 Elsevier B.V.

Mathematics

Operations Research Letters

A discrete variant of Farkas’ Lemma

Adv. Mater. 2017, 29, 1700244 In Figure 2d of the originally published article, the (+) and (−) labels denoting the presence or absence of linker DNA were placed over the wrong samples. The figure is corrected here:. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Fulltext

Advanced Materials

Correction to: Gold and Hairpin DNA Functionalization of Upconversion Nanocrystals for Imaging and In Vivo Drug Delivery (Advanced Materials, (2017), 29, 18, (1700244), 10.1002/adma.201700244)

We have discussed the possibility where the observed deviations in the b → sµ+µ− data including the variables RK(*) are addressed, in the context of vectorlike compositeness (or so called hypercolor). Major virtues of this type of scenario are as follows: (i) The theory is manifestly gauge anomaly free; (ii) A desirable form in flavor-changing interactions is naturally realized by exchanges of the hypercolor vector ρ mesons, which are composite spin-1 particles being analogous to the vector ρ mesons in the quantum chromodynamics. We can address the RK(*) anomaly consistently, while negligible effects happen in the observables RRD(*) due to the structure of a global symmetry in the scenario. © Copyright owned by the author(s) under the terms of the Creative Commons.

Physics

Proceedings of Science

Vector-like compositeness meets B-physics RK(*) anomaly

We report electron-hole conduction asymmetry in monolayer graphene. Previously, it has been claimed that electron-hole conduction asymmetry is due to imbalanced carrier injection from metallic electrodes. Here, we show that metallic contacts have negligible impact on asymmetric conduction and may be either sample or device-dependent phenomena. Electrical measurements show that monolayer graphene based devices exhibit suppressed electron conduction compared to hole conduction due to the presence of donor impurities which scatter electrons more efficiently. This can be explained by the relativistic nature of charge carriers in a graphene monolayer and can be reconciled with the fact that in a relativistic quantum system transport cross section does depend on the sign of scattering potential in contrast to a nonrelativistic quantum system. © 2017 American Physical Society.

Physical Review B

Relativistic nature of carriers: Origin of electron-hole conduction asymmetry in monolayer graphene

Nitrogen heteroarenes form an important class of compounds which can be found in natural products, synthetic drugs, building blocks etc. Among the diverse strategies that were developed for the synthesis of nitrogen heterocycles, oxidative dehydrogenation is extremely effective. This review discusses various oxidative dehydrogenation strategies of C-C and C-N bonds to generate nitrogen heteroarenes from their corresponding heterocyclic substrates. The strategies are categorized under stoichiometric and catalytic usage of reagents that facilitate such transformations. The application of these strategies in the synthesis of nitrogen heteroarene natural products and synthetic drug intermediates are also discussed. We hope this review will arouse sufficient interest among the scientific community to further advance the application of oxidative dehydrogenation in the synthesis of nitrogen heteroarenes. © 2017 Hati et al.; Licensee Beilstein-Institut.

Beilstein Journal of Organic Chemistry

Oxidative dehydrogenation of C-C and C-N bonds: A convenient approach to access diverse (dihydro)heteroaromatic compounds

DNA polymerases are essential enzymes that faithfully and efficiently replicate genomic information.1-3 The mechanism of nucleotide incorporation by DNA polymerases has been extensively studied structurally and kinetically, but several key steps following phosphodiester bond formation remain structurally uncharacterized due to utilization of natural nucleotides. It is thought that the release of pyrophosphate (PPi) triggers reverse conformational changes in a polymerase in order to complete a full catalytic cycle as well as prepare for DNA translocation and subsequent incorporation events. Here, by using the triphosphates of chain-terminating antiviral drugs lamivudine ((-)3TC-TP) and emtricitabine ((-)FTC-TP), we structurally reveal the correct sequence of post-chemistry steps during nucleotide incorporation by human DNA polymerase $\beta$ (hPol$\beta$) and provide a structural basis for PPi release. These post-catalytic structures reveal hPol$\beta$ in an open conformation with PPi bound in the active site, thereby strongly suggesting that the reverse conformational changes occur prior to PP; release. The results also help to refine the role of the newly discovered third divalent metal ion for DNA polymerase-catalyzed nucleotide incorporation. Furthermore, a post-chemistry structure of hPol$\beta$ in the open conformation, following incorporation of (-)3TC-MP, with a second (-)3TC-TP molecule bound to the active site in the absence of PPi, suggests that nucleotide binding stimulates PPi dissociation and occurs before polymerase translocation. Our structural characterization defines the order of the elusive post-chemistry steps in the canonical mechanism of a DNA polymerase.

Life Sciences

Journal of the American Chemical Society

Structural insights into the post-chemistry steps of nucleotide incorporation catalyzed by a DNA polymerase

Microbial load of nurses’ white coats in a hospital was determined on polyester cotton blend and polyester fabric after the first and second work shift. Contamination on the blend fabric was significantly higher (P < .05) than on polyester. After the second shift, bacterial colonies on polyester and blend fabrics increased by ~98\% and ~70\%, respectively. Among the isolates detected on polyester after the second shift, Escherichia coli was the most abundant (47.8\%), followed by staphylococci (19.1\%). © 2017 Association for Professionals in Infection Control and Epidemiology, Inc.

American Journal of Infection Control

Bacterial contamination of nurses’ white coats after first and second shift

Unraveling transcriptional heterogeneity and the labyrinthine nature of neurodevelopment can probe insights into neuropsychiatric disorders. It is noteworthy that adult neurogenesis is restricted to the subventricular and subgranular zones of the brain. Recent studies suggest long non-coding RNAs (lncRNAs) as an avant-garde class of regulators implicated in neurodevelopment. But, paucity exists in the knowledge regarding lncRNAs in neurogenesis and their associations with neurodevelopmental defects. To address this, we extensively reviewed the existing literature databases as well as performed relevant in-silico analysis. We utilized Allen Brain Atlas (ABA) differential search module and generated a catalogue of ∼30,000 transcripts specific to the neurogenic zones, including coding and non-coding transcripts. To explore the existing lncRNAs reported in neurogenesis, we performed extensive literature mining and identified 392 lncRNAs. These degenerate lncRNAs were mapped onto the ABA transcript list leading to detection of 20 lncRNAs specific to neurogenic zones (Dentate gyrus/Lateral ventricle), among which 10 showed associations to several neurodevelopmental disorders following in-silico mapping onto brain disease databases like Simons Foundation Autism Research Initiative, AutDB, and lncRNADisease. Notably, using ABA correlation module, we could establish lncRNA-to-mRNA coexpression networks for the above 10 candidate lncRNAs. Finally, pathway prediction revealed physical, biochemical, or regulatory interactions for nine lncRNAs. In addition, ABA differential search also revealed 54 novel significant lncRNAs from the null set (∼30,000). Conclusively, this review represents an updated catalogue of lncRNAs in neurogenesis and neurological diseases, and overviews the field of OMICs-based data analysis for understanding lncRNome-based regulation in neurodevelopment. © 2017, Mary Ann Liebert, Inc.

Stem Cells and Development

Decoding Crucial LncRNAs Implicated in Neurogenesis and Neurological Disorders

Visceral Leishmaniasis is a deadly parasitic disease caused by Leishmania donovani. Paucity exists in the discovery of novel chemotherapeutics against Leishmaniasis. In this study, we synthesized a natural product inspired Diversity Oriented Synthesis library of L. donovani Trypanothione reductase (LdTR) inhibitor β-carboline-quinazolinone hybrids, which are different in stereochemical architecture and diverse in the bioactive chemical space. It is noteworthy that chirality affects drug-to-protein binding affinity since proteins in any living system are present only in one of the chiral forms. Upon evaluation of the hybrids, one of the chiral forms i.e. Compound 1 showed profound cytotoxic effect in micromolar range as compared to its other chiral form i.e. Compound 2. In-silico docking studies confirmed high binding efficiency of Compound 1 with the catalytic pocket of LdTR. Treatment of L. donovani parasites with Compound 1 inhibits LdTR activity, induces imbalance in redox homeostasis by enhancing ROS, disrupts the mitochondrial membrane potential, modifies actin polymerization and alters the surface topology and architecture. All these cellular modifications eventually led to apoptosis-like death of promastigotes. Furthermore, we synthesized the analogues of Compound 1 and found that these compounds show profound antileishmanial activity in the nanomolar range both in promastigotes and intracellular amastigotes. The enhanced inhibitory potential of these compounds was further supported by in-silico analysis of protein-ligand interactions which revealed high binding efficiency towards the catalytic pocket of LdTR. Taken together, this study reports the serendipitous discovery of β-carboline-quinazolinone hybrids with enhanced antileishmanial activity along with the in-depth structure-activity relationships and mechanism of action of these analogues. © 2016 Elsevier Inc.