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Chauhan I.S.,CSIR Central Drug Research Institute | Kaur J.,Shri Ram Murti Smarak Institute of Medical science | Krishna S.,CSIR Central Drug Research Institute | Ghosh A.,Xcelris Genomics | And 3 more authors.
BMC Evolutionary Biology | Year: 2015

Background: Leptomonas is monogenetic kinetoplastid parasite of insects and is primitive in comparison to Leishmania. Comparative studies of these two kinetoplastid may share light on the evolutionary transition to dixenous parasitism in Leishmania. In order to adapt and survive within two hosts, Leishmania species must have acquired virulence factors in addition to mechanisms that mediate susceptibility/resistance to infection in the pathology associated with disease. Rab proteins are key mediators of vesicle transport and contribute greatly to the evolution of complexity of membrane transport system. In this study we used our whole genome sequence data of these two divergent kinetoplastids to analyze the orthologues/paralogues of Rab proteins. Results: During change of lifestyle from monogenetic (Leptomonas) to digenetic (Leishmania), we found that the prenyl machinery remained unchanged. Geranylgeranyl transferase-I (GGTase-I) was absent in both Leishmania and its sister Leptomonas. Farnesyltransferase (FTase) and geranylgeranyl transferase-II (GGTase-II) were identified for protein prenylation. We predict that activity of the missing alpha-subunit (aα-subunit) of GGTase-II in Leptomonas was probably contributed by the aα-subunit of FTase, while beta-subunit (β-subunit) of GGTase-II was conserved and indicated functional conservation in the evolution of these two kinetoplastids. Therefore the β-subunit emerges as an excellent target for compounds inhibiting parasite activity in clinical cases of co-infections. We also confirmed that during the evolution to digenetic life style in Leishmania, the parasite acquired capabilities to evade drug action and maintain parasite virulence in the host with the incorporation of short-chain dehydrogenase/reductase (SDR/MDR) superfamily in Rab genes. Conclusion: Our study based on whole genome sequences is the first to build comparative evolutionary analysis and identification of prenylation proteins in Leishmania and its sister Leptomonas. The information presented in our present work has importance for drug design targeted to kill L. donovani in humans but not affect the human form of the prenylation enzymes. © 2015 Chauhan et al. Source


Singh N.,CSIR - Central Electrochemical Research Institute | Chikara S.,Xcelris Genomics | Sundar S.,Banaras Hindu University
PLoS ONE | Year: 2013

Background: Known as 'neglected disease' because relatively little effort has been applied to finding cures, leishmaniasis kills more than 150,000 people every year and debilitates millions more. Visceral leishmaniasis (VL), also called Kala Azar (KA) or black fever in India, claims around 20,000 lives every year. Whole genome analysis presents an excellent means to identify new targets for drugs, vaccine and diagnostics development, and also provide an avenue into the biological basis of parasite virulence in the L. donovani complex prevalent in India. Methodology/Principal Findings: In our presently described study, the next generation SOLiD™ platform was successfully utilized for the first time to carry out whole genome sequencing of L. donovani clinical isolates from India. We report the exceptional occurrence of insect trypanosomatids in clinical cases of visceral leishmaniasis (Kala Azar) patients in India. We confirm with whole genome sequencing analysis data that isolates which were sequenced from Kala Azar (visceral leishmaniasis) cases were genetically related to Leptomonas. The co-infection in splenic aspirate of these patients with a species of Leptomonas and how likely is it that the infection might be pathogenic, are key questions which need to be investigated. We discuss our results in the context of some important probable hypothesis in this article. Conclusions/Significance: Our intriguing results of unusual cases of Kala Azar found to be most similar to Leptomonas species put forth important clinical implications for the treatment of Kala Azar in India. Leptomonas have been shown to be highly susceptible to several standard leishmaniacides in vitro. There is very little divergence among these two species viz. Leishmania sp. and L. seymouri, in terms of genomic sequence and organization. A more extensive perception of the phenomenon of co-infection needs to be addressed from molecular pathogenesis and eco-epidemiological standpoint. © 2013 Singh et al. Source


Debnath M.,Central University of Rajasthan | Pandey M.,Xcelris Genomics | Bisen P.S.,Jiwaji University
OMICS A Journal of Integrative Biology | Year: 2011

Abiotic stress can lead to changes in development, productivity, and severe stress and may even threaten survival of plants. Several environmental stresses cause drastic changes in the growth, physiology, and metabolism of plants leading to the increased accumulation of secondary metabolites. As medicinal plants are important sources of drugs, steps are taken to understand the effect of stress on the physiology, biochemistry, genomic, proteomic, and metabolic levels. The molecular responses of plants to abiotic stress are often considered as a complex process. They are mainly based on the modulation of transcriptional activity of stress-related genes. Many genes have been induced under stress conditions. The products of stress-inducible genes protecting against these stresses includes the enzymes responsible for the synthesis of various osmoprotectants. Genetic engineering of tolerance to abiotic stresses help in molecular understanding of pathways induced in response to one or more of the abiotic stresses. Systems biology and virtual experiments allow visualizing and understanding how plants work to overcome abiotic stress. This review discusses the omic approach to understand the plant response to abiotic stress with special emphasis on medicinal plant. © Copyright 2011, Mary Ann Liebert, Inc. Source


Sharma R.,Rani Durgavati University | Sharma R.,Tropolite Foods Pvt Ltd | Sanodiya B.S.,Tropolite Foods Pvt Ltd | Bagrodia D.,Tropolite Foods Pvt Ltd | And 4 more authors.
International Journal of Pharma and Bio Sciences | Year: 2012

Lactic acid bacteria are safe microorganisms that are capable of providing healthy conditions to human beings and animals. They might be effective in exerting beneficial effects on human host in terms of maintenance of homeostasis and promotion of health. Some studies suggest that fermented food products of the bacteria provide better digestibility, nutrient assimilation and effects on constipation. The anti-microbial, anti-allergic, anti-inflammatory and anti-viral activity against urogenital and respiratory infections expresses the ability of the microbe to resist pathogens while immunomodulatory, lactose intolerance, hypocholesterolemic, anti-cancerous, prevention from dairrhoea, tooth decay, stomach ulcers and various other gastrointestinal problems results in an approach towards improved health conditions. The metabolites from the microbe; bacteriocins are very common in food industry with their ability to preserve food products for longer times. Modern science also suggests the use of lactic acid bacteria as live vaccines. There is a need to reconcile the applications and tremendous approach of lactic acid bacteria, which will provide a broader view of its potential in health modulation. Source


Thakur G.S.,Tropilite Foods Pvt. Ltd | Sharma R.,Tropilite Foods Pvt. Ltd | Sanodiya B.S.,Tropilite Foods Pvt. Ltd | Pandey M.,Xcelris Genomics | And 3 more authors.
Journal of Applied Pharmaceutical Science | Year: 2012

Gymnema sylvestre (Asclepiadaceae) also known as 'gurmar' or 'sugar destroyer' is a woody, climbing traditional medicinal herb which has many therapeutic applications in Ayurvedic system of medicine. It is used for lowering serum cholesterol, triglycerides and blood glucose level (hypoglycemic or antihyperglycemic), hypolipidaemic, weight loss, stomach ailments, constipation, water retention and liver diseases, either high or low blood pressure, tachycardia or arrhythmias, and used as aperitive, purgative, in eye troubles, antiinflammatory, smooth muscle relaxant, prevention of dental caries, cataract and as anticancer-cytotoxic agent. Its flowers, leaves, and fruits contains alkaloids, flavones, saponins, sapogenins, anthraquinones, hentri-acontane, pentatriacontane, a and ß-chlorophylls, phytin, resins, d-quercitol, tartaric acid, formic acid, butyric acid, lupeol, ß-amyrin related glycosides and stigmasterol having main principle bioactive compunds viz. gymnemic acids, gymnemasides, gymnemagenin, gurmarin, gymnemosides, gymnemanol, gymnemasins, gypenoside, and conduritol which act as therapeutic agent and play vital role in many therapeutic applications. Gymnemic acids are thought to be responsible for its antidiabetic activity and it is the major component of an extract shown to stimulate insulin release from the pancreas. Another anti-sweet agent gumarin is utilized as a pharmacological tool in the study of sweet-taste transduction. The commercial exploitation of this plant and their secondary metabolites are some of the major prospective of this rare medicinal herb. The focus of the present review is to achieve the potential of therapeutic value of this herb and mechanism and action of their secondary metabolites. Source

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