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Bharati K.,Translational Health Science and Technology Institute | Bhattacharya S.K.,Indian Council of Medical Research
Current Topics in Microbiology and Immunology | Year: 2014

This chapter highlights the cholera situation in South Asia and the Bay of Bengal region, the original 'homeland' of cholera. A detailed discussion of cholera outbreaks in individual countries in South-East Asia follows. The countries of the World Health Organization (WHO) SEARO (South-East Asia Region) region are discussed first, followed by discussions about the other countries in South-East Asia that do not fall within the purview of the WHO SEARO classification of the member countries of the region. Therefore, the chapter attempts to provide a comprehensive yet precise outline of the major cholera outbreaks that have occurred in the region over the years. © 2014 Springer-Verlag Berlin Heidelberg. Source

Das S.,Translational Health Science and Technology Institute
Current Protein and Peptide Science | Year: 2015

Integrase interactor 1 (INI1/hSNF5) is a core component of the SWI/SNF chromatin remodeling complex that alters the structure of chromatin in order to facilitate DNA-dependent cellular processes like transcription, replication, and repair. INI1/hSNF5 plays an important role in a variety of cellular processes. Inactivation of the Snf5 gene in mice leads to embryonic lethality suggesting a critical role for INI1/hSNF5 in cellular function, viability, and development. Biallelic loss-of-function of INI1/hSNF5 leads to certain cancers, most frequently rhabdoid tumors, demonstrating that INI1/hSNF5 is a tumor suppressor gene. INI1/hSNF5 regulates several essential steps in the propagation of the HIV-1 virus within the host cell, particularly HIV-1 integration. The mode of function of INI1/hSNF5 is only beginning to be understood. Given its importance in the normal functioning of the cell and its association with two diseases with high morbidity and mortality rates, it is imperative that the functions of this protein is delineated in greater detail in order to develop therapeutic interventions in certain cancers and AIDS. In this review, I have summarized the literature of published results on INI1/hSNF5 with emphasis on its molecular organization, role in different cellular pathways and involvement in AIDS and cancer. © 2015 Bentham Science Publishers. Source

Midonet C.,CNRS Institute of Integrative Biology | Das B.,Translational Health Science and Technology Institute | Sherratt D.J.,University of Oxford
Proceedings of the National Academy of Sciences of the United States of America | Year: 2014

As in most bacteria, topological problems arising from the circularity of the two Vibrio cholerae chromosomes, chrI and chrII, are resolved by the addition of a crossover at a specific site of each chromosome, dif, by two tyrosine recombinases, XerC and XerD. The reaction is under the control of a cell division protein, FtsK, which activates the formation of a Holliday Junction (HJ) intermediate by XerD catalysis that is resolved into product by XerC catalysis. Many plasmids and phages exploit Xer recombination for dimer resolution and for integration, respectively. In all cases so far described, they rely on an alternative recombination pathway in which XerC catalyzes the formation of a HJ independently of FtsK. This is notably the case for CTXφ, the cholera toxin phage. Here, we show that in contrast, integration of TLCφ, a toxin-linked cryptic satellite phage that is almost always found integrated at the chrI dif site before CTXφ, depends on the formation of a HJ by XerD catalysis, which is then resolved by XerC catalysis. The reaction nevertheless escapes the normal cellular control exerted by FtsK on XerD. In addition, we show that the same reaction promotes the excision of TLCφ, along with any CTXφ copy present between dif and its left attachment site, providing a plausible mechanism for how chrI CTXφ copies can be eliminated, as occurred in the second wave of the current cholera pandemic. Source

Appaiahgari M.B.,Translational Health Science and Technology Institute | Vrati S.,Translational Health Science and Technology Institute | Vrati S.,National Institute of Immunology
Expert Review of Vaccines | Year: 2010

Japanese encephalitis (JE) is a disease of the CNS caused by Japanese encephalitis virus (JEV). The disease appears in the form of frequent outbreaks in most south- and southeast Asian countries and the virus has become endemic in several areas. There is no licensed therapy available and disease control by vaccination is considered to be most effective. Mouse brain-derived inactivated JE vaccines, although immunogenic, have several limitations in terms of safety, availability and requirement for multiple doses. Owing to these drawbacks, the WHO called for the development of novel, safe and more efficacious JE vaccines. Several candidate vaccines have been developed and at least three of them that demonstrated strong immunogenicity after one or two doses of the vaccine in animal models were subsequently tested in various clinical trials. One of these vaccines, IMOJEV® (JE-CV and previously known as ChimeriVax™-JE), is a novel recombinant chimeric virus vaccine, developed using the Yellow fever virus (YFV) vaccine vector YFV17D, by replacing the cDNA encoding the envelope proteins of YFV with that of an attenuated JEV strain SA14-14-2. IMOJEV was found to be safe, highly immunogenic and capable of inducing long-lasting immunity in both preclinical and clinical trials. Moreover, a single dose of IMOJEV was sufficient to induce protective immunity, which was similar to that induced in adults by three doses of JE-VAX®, a mouse brain-derived inactivated JE vaccine. Recently, Phase III trials evaluating the immunogenicity and safety of the chimeric virus vaccine have been successfully completed in some JE-endemic countries and the vaccine manufacturers have filed an application for vaccine registration. IMOJEV may thus be licensed for use in humans as an improved alternative to the currently licensed JE vaccines. © 2010 Expert Reviews Ltd. Source

Choudhary E.,Translational Health Science and Technology Institute | Bishai W.,Johns Hopkins University | Agarwal N.,Translational Health Science and Technology Institute
PLoS ONE | Year: 2014

Mycobacterium tuberculosis (Mtb) secretes excess of a second messenger molecule, 3',5'-cyclic AMP (cAMP), which plays a critical role in the survival of Mtb in host macrophages. Although Mtb produces cAMP in abundance, its exact role in the physiology of mycobacteria is elusive. In this study we have analyzed the expression of 16 adenylate cyclases (ACs) and kinetics of intracellular cAMP levels in Mtb during in vitro growth under the regular culture conditions, and after exposure to different stress agents. We observed a distinct expression pattern of these ACs which is correlated with intracellular cAMP levels. Interestingly cAMP levels are significantly elevated in Mtb following heat stress, whereas other stress conditions such as oxidative, nitrosative or low pH do not affect intracellular cAMP pool in vitro. A significant increase in expression by > 2- fold of five ACs namely Rv1647, Rv2212, Rv1625c, Rv2488c and Rv0386 after heat stress further suggested that cAMP plays an important role in controlling Mtb response to heat stress. In the light of these observations, effect of exogenous cAMP on global gene expression profile was examined by using microarrays. The microarray gene expression analysis demonstrated that cAMP regulates expression of a subset of heat stress-induced genes comprising of dnaK, grpE, dnaJ, and Rv2025c. Further we performed electrophoretic mobility shift assay by using cAMP-receptor protein of Mtb (CRPM), which demonstrated that CRPM specifically recognizes a sequence 2301AGCGACCGTCAGCACG2286 in 5'-untranslated region of dnaK. © 2014 Choudhary et al. Source

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