Host Factor Nucleophosmin 1 (NPM1/B23) Exerts Antiviral Effects against Chikungunya Virus by Its Interaction with Viral Nonstructural Protein 3.

Chikungunya virus (CHIKV) hijacks host cell machinery to support its replication. Nucleophosmin 1 (NPM1/B23), a nucleolar phosphoprotein, is one of the host proteins known to restrict CHIKV infection; however, the mechanistic details of the antiviral role of NPM1 are not elucidated. It was seen in our experiments that the level of NPM1 expression affected the expression levels of interferon-stimulated genes (ISGs) that play antiviral roles in CHIKV infection, such as , , , and , indicating that one of the antiviral mechanisms could be through modulation of interferon-mediated pathways.

Novel small synthetic HIV-1 V3 crown variants: CCR5 targeting ligands.

The CC chemokine receptor 5 (CCR5) antagonism represents a promising pharmacological strategy for therapeutic intervention as it plays a significant role in reducing the severity and progression of a wide range of pathological conditions. Here we designed and generated peptide ligands targeting the chemokine receptor, CCR5, that were derived from the critical interaction sites of the V3 crown domain of envelope protein glycoprotein gp120 (TRKSIHIGPGRAFYTTGEI) of HIV-1 using computational biology approach and the peptide sequence corresponding to this region was taken as the template peptide, designated as TMP-1. The peptide variants were synthesized by employing Fmoc chemistry using polymer support and were labelled with rhodamine B to study their interaction with the CCR5 receptor expressed on various cells.

Genomic attributes differ between Vibrio parahaemolyticus environmental and clinical isolates including pathotypes.

Vibrio parahaemolyticus is a marine bacterium and causes opportunistic gastroenteritis in humans. Clinical strains of V. parahaemolyticus contain haemolysin and type III secretion systems (T3SS) that define their pathotype.

Low Abundance in the Lower Gut Microbiota Is Associated With -Related Gastric Ulcer and Gastric Cancer.

infection in stomach leads to gastric cancer, gastric ulcer, and duodenal ulcer. More than 1 million people die each year due to these diseases, but why most -infected individuals remain asymptomatic while a certain proportion develops such severe gastric diseases remained an enigma. Several studies indicated that gastric and intestinal microbiota may play a critical role in the development of the -associated diseases.

Pax6 modulates intra-retinal axon guidance and fasciculation of retinal ganglion cells during retinogenesis.

Intra-retinal axon guidance involves a coordinated expression of transcription factors, axon guidance genes, and secretory molecules within the retina. Pax6, the master regulator gene, has a spatio-temporal expression typically restricted till neurogenesis and fate-specification. However, our observation of persistent expression of Pax6 in mature RGCs led us to hypothesize that Pax6 could play a major role in axon guidance after fate specification.

Adaptive laboratory evolution of Vibrio cholerae to doxycycline associated with spontaneous mutation.

Cholera, caused by the Gram-negative bacterium Vibrio cholerae, remains a serious threat in underdeveloped countries. Although rehydration therapy has been the mainstay of disease management, antibiotics are also being used as an adjunct treatment, resulting in an increase in the circulation of antimicrobial-resistant V. cholerae strains.

Prospects of multitarget drug designing strategies by linking molecular docking and molecular dynamics to explore the protein-ligand recognition process.

The designing of drugs that can simultaneously affect different protein targets is one novel and promising way to treat complex diseases. Multitarget drugs act on multiple protein receptors each implicated in the same disease state, and may be considered to be more beneficial than conventional drug therapies. For example, these drugs can have improved therapeutic potency due to synergistic effects on multiple targets, as well as improved safety and resistance profiles due to the combined regulation of potential primary therapeutic targets and compensatory elements and lower dosage typically required.

Molecular trail for the anticancer behavior of a novel copper carbohydrazone complex in BRCA1 mutated breast cancer.

Novel chelated metal complexes were synthesized from carbohydrazones to thiocarbohydrazones using metal-based drug designing platforms and their combination effect with Pb, a naphthaquinone were analyzed for anticancer activity in breast cancer cell lines. A panel of BRCA1 wild-type and mutated breast cancer cells: MCF-7 (BRCA1 /ER ), MDA-MB-231 (BRCA1 /ERα ), HCC-1937 (BRCA1 /ERα ), HCC1937/wt BRCA1, MX1 (BRCA1 /ERα ), and MDA-MB-436 (BRCA1 /ERα ) were screened for anti-cancer activity. Cu (HL)(HSO ) · H O]SO  · 6 H O (CS2) is the most potent anticancer agent among the copper carbohydrazone and thiocarbohydrazone complexes analyzed in this study.

miR Cluster 143/145 Directly Targets Nrl and Regulates Rod Photoreceptor Development.

Retinal histogenesis requires coordinated and temporal functioning of factors by which different cell types are generated from multipotent progenitors. Development of rod photoreceptors is regulated by multiple transcription factors, and Nrl is one of the major factors involved in their fate specification. Presence or absence of Nrl at the postnatal stages decides the generation of cone photoreceptors or other later retinal cells.

The multiple stress responsive transcriptional regulator Rv3334 of Mycobacterium tuberculosis is an autorepressor and a positive regulator of kstR.

Rv3334 protein of Mycobacterium tuberculosis belongs to the MerR family of transcriptional regulators and is upregulated during hypoxia and other stress conditions. Employing GFP reporter constructs, mobility shift assays and ChIP assays, we demonstrate that Rv3334 binds to its own promoter and acts as an autorepressor. We were able to locate a 22 bp palindrome in its promoter that we show to be the cognate binding sequence of Rv3334.

Correlation of phylogenetic clade diversification and in vitro infectivity differences among Cosmopolitan genotype strains of Chikungunya virus.

Cosmopolitan genotypes of Chikungunya virus caused the large-scale febrile disease outbreaks in the last decade in Asian and African continents. Molecular analyses of these strains had revealed significant genetic diversification and occurrence of novel mosquito-adaptive mutations. In the present study we looked into whether the genetic diversification has implications in the infectivity phenotype.

A systems biology approach to model neural stem cell regulation by notch, shh, wnt, and EGF signaling pathways.

The Notch, Sonic Hedgehog (Shh), Wnt, and EGF pathways have long been known to influence cell fate specification in the developing nervous system. Here we attempted to evaluate the contemporary knowledge about neural stem cell differentiation promoted by various drug-based regulations through a systems biology approach. Our model showed the phenomenon of DAPT-mediated antagonism of Enhancer of split [E(spl)] genes and enhancement of Shh target genes by a SAG agonist that were effectively demonstrated computationally and were consistent with experimental studies.

PKSIIIexplorer: TSVM approach for predicting Type III polyketide synthase proteins.

Unlabelled: PKSIIIexplorer, a web server based on 'transductive Support Vector Machine' allows fast and reliable prediction of Type III polyketide synthase proteins. It provides a simple unique platform to identify the probability of a particular sequence, being a type III polyketide synthases or not with moderately high accuracy. We hope that our method could serve as a useful program for the type III polyketide researchers.

Molecular dynamics simulation studies and in vitro site directed mutagenesis of avian beta-defensin Apl_AvBD2.

Background: Defensins comprise a group of antimicrobial peptides, widely recognized as important elements of the innate immune system in both animals and plants. Cationicity, rather than the secondary structure, is believed to be the major factor defining the antimicrobial activity of defensins. To test this hypothesis and to improve the activity of the newly identified avian beta-defensin Apl_AvBD2 by enhancing the cationicity, we performed in silico site directed mutagenesis, keeping the predicted secondary structure intact.