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Thiruvananthapuram, India

Chandra V.,Kerala University | Chandra V.,College of Engineering, Trivandrum | Girijadevi R.,Translational Cancer Research Laboratory | Nair A.S.,Kerala University | Pillai R.M.,Translational Cancer Research Laboratory
BMC Bioinformatics | Year: 2010

Background: MicroRNAs (miRNAs) play an essential task in gene regulatory networks by inhibiting the expression of target mRNAs. As their mRNA targets are genes involved in important cell functions, there is a growing interest in identifying the relationship between miRNAs and their target mRNAs. So, there is now a imperative need to develop a computational method by which we can identify the target mRNAs of existing miRNAs. Here, we proposed an efficient machine learning model to unravel the relationship between miRNAs and their target mRNAs.Results: We present a novel computational architecture MTar for miRNA target prediction which reports 94.5% sensitivity and 90.5% specificity. We identified 16 positional, thermodynamic and structural parameters from the wet lab proven miRNA:mRNA pairs and MTar makes use of these parameters for miRNA target identification. It incorporates an Artificial Neural Network (ANN) verifier which is trained by wet lab proven microRNA targets. A number of hitherto unknown targets of many miRNA families were located using MTar. The method identifies all three potential miRNA targets (5' seed-only, 5' dominant, and 3' canonical) whereas the existing solutions focus on 5' complementarities alone.Conclusion: MTar, an ANN based architecture for identifying functional regulatory miRNA-mRNA interaction using predicted miRNA targets. The area of target prediction has received a new momentum with the function of a thermodynamic model incorporating target accessibility. This model incorporates sixteen structural, thermodynamic and positional features of residues in miRNA: mRNA pairs were employed to select target candidates. So our novel machine learning architecture, MTar is found to be more comprehensive than the existing methods in predicting miRNA targets, especially human transcritome. © 2010 Chandra et al; licensee BioMed Central Ltd.

Krishnan V.,Sri Sankara Dental College | Krishnan A.,Translational Cancer Research Laboratory | Remya R.,Kerala University | Ravikumar K.K.,Indian National Institute for Interdisciplinary Science and Technology | And 5 more authors.
Acta Biomaterialia | Year: 2011

The present research was aimed at developing surface coatings on β titanium orthodontic archwires capable of protection against fluoride-induced corrosion. Cathodic arc physical vapor deposition PVD (CA-PVD) and magnetron sputtering were utilized to deposit thin films of titanium aluminium nitride (TiAlN) and tungsten carbide/carbon (WC/C) coatings on β titanium orthodontic archwires. Uncoated and coated specimens were immersed in a high fluoride ion concentration mouth rinse, following a specially designed cycle simulating daily use. All specimens thus obtained were subjected to critical evaluation of parameters such as electrochemical corrosion behaviour, surface analysis, mechanical testing, microstructure, element release, and toxicology. The results confirm previous research that β titanium archwires undergo a degradation process when in contact with fluoride mouth rinses. The study confirmed the superior nature of the TiAlN coating, evident as many fewer changes in properties after fluoride treatment when compared with the WC/C coating. Thus, coating with TiAlN is recommended in order to reduce the corrosive effects of fluorides on β titanium orthodontic archwires. © 2010 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Sreekumar E.,Rajiv Gandhi Center for Biotechnology | Issac A.,Rajiv Gandhi Center for Biotechnology | Nair S.,Rajiv Gandhi Center for Biotechnology | Hariharan R.,Translational Cancer Research Laboratory | And 7 more authors.
Virus Genes | Year: 2010

Chikungunya virus (CHIKV), a positive-stranded alphavirus, causes epidemic febrile infections characterized by severe and prolonged arthralgia. In the present study, six CHIKV isolates (2006 RGCB03, RGCB05; 2007 RGCB80, RGCB120; 2008 RGCB355, RGCB356) from three consecutive Chikungunya outbreaks in Kerala, South India, were analyzed for genetic variations by sequencing the 11798 bp whole genome of the virus. A total of 37 novel mutations were identified and they were predominant in the 2007 and 2008 isolates among the six isolates studied. The previously identified E1 A226V critical mutation, which enhances mosquito adaptability, was present in the 2007 and 2008 samples. An important observation was the presence of two coding region substitutions, leading to nsP2 L539S and E2 K252Q change. These were identified in three isolates (2007 RGCB80 and RGCB120; 2008 RGCB355) by full-genome analysis, and also in 13 of the 31 additional samples (42%), obtained from various parts of the state, by sequencing the corresponding genomic regions. These mutations showed 100% co-occurrence in all these samples. In phylogenetic analysis, formation of a new genetic clade by these isolates within the East, Central and South African (ECSA) genotypes was observed. Homology modeling followed by mapping revealed that at least 20 of the identified mutations fall into functionally significant domains of the viral proteins and are predicted to affect protein structure. Eighteen of the identified mutations in structural proteins, including the E2 K252Q change, are predicted to disrupt T-cell epitope immunogenicity. Our study reveals that CHIK virus with novel genetic changes were present in the severe Chikungunya outbreaks in 2007 and 2008 in South India. © 2009 Springer Science+Business Media, LLC.

Kartik R.,Translational Cancer Research Laboratory | Kartik R.,National Botanical Research Institute | Rao C.V.,Translational Cancer Research Laboratory | Rao C.V.,National Botanical Research Institute | And 3 more authors.
Indian Journal of Pharmacology | Year: 2010

Objective: The prevalence of oxidative stress may be implicated in the etiology of many pathological conditions. Protective antioxidant action imparted by many plant extracts and plant products make them a promising therapeutic drug for free-radical-induced pathologies. In this study, we assessed the antioxidant potential and suppressive effects of Achyranthes aspera by evaluating the hepatic diagnostic markers on chemical-induced hepatocarcinogenesis. Materials and Methods: The in vivo model of hepatocarcinogenesis was studied in Swiss albino rats. Experimental rats were divided into five groups: control, positive control (NDEA and CCl 4 ), A. aspera treated (100, 200, and 400 mg/kg b.w.). At 20 weeks after the administration of NDEA and CCl 4 , treated rats received A. aspera extract (AAE) at a dose of 100, 200, and 400 mg/kg once daily route. At the end of 24 weeks, the liver and relative liver weight and body weight were estimated. Lipid peroxidation (LPO), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST), and reduced glutathione (GSH) were assayed. The hepatic diagnostic markers namely serum glutamic oxaloacetic transminase (AST), serum glutamic pyruvate transminase (ALT), serum alkaline phosphatase (ALP), gamma glutamyl transpeptidase (GGT), and bilirubin (BL) were also assayed, and the histopathological studies were investigated in control, positive control, and experimental groups. Results: The extract did not show acute toxicity and the per se effect of the extract showed decrease in LPO, demonstrating antioxidant potential and furthermore no change in the hepatic diagnosis markers was observed. Administration of AAE suppressed hepatic diagnostic and oxidative stress markers as revealed by decrease in NDEA and CCl 4 -induced elevated levels of SGPT, SGOT, SALP, GGT, bilirubin, and LPO. There was also a significant elevation in the levels of SOD, CAT, GPx, GST, and GSH as observed after AAE treatment. The liver and relative liver weight were decreased after treatment with AAE in comparison to positive control group. The architecture of hepatic tissue was normalized upon treatment with extract at different dose graded at 100, 200, and 400 mg/kg. b.w. in comparison to positive control group. Conclusion: These results suggest that A. aspera significantly alleviate hepatic diagnostic and oxidative stress markers which signify its protective effect against NDEA and CCl 4 -induced two-stage hepatocarcinogenesis.

Krishnan A.,Translational Cancer Research Laboratory | Nair S.A.,Translational Cancer Research Laboratory | Pillai M.R.,Translational Cancer Research Laboratory
Journal of Cellular and Molecular Medicine | Year: 2010

Genetic and biochemical studies have provided considerable insight into the multiple functions of cyclin-dependent kinase subunit (cks)1 in cell division cycle. In addition to enhanced substrate targeting by specific ubiquitin ligases SCFskp2 and APC/C, its direct interaction with proteasome components normalizes multiple cell cycle regulators. Importantly, it also acts as a transcriptional regulator. cks1 overexpression reflects poor prognosis in malignancy thus indicating its possible role in tumour diagnosis and management. The present review compiles the multiple functional roles of cks1 in cell division with specific emphasis on its molecular mechanisms. Its docking functions and the possible downstream proteolytic and transcriptional targets are described. The spatial configuration of cks1-cdk2 complex and the structural organization of cks1-p27-skp2 assembly required for p27 ubiquitination are discussed in detail. In addition to enhanced p27 degradation, the possible other mechanisms which underlie its pathological functions in human cancer progression are also discussed. Though there are apparent gaps in information, the turnover mechanism of cks1 is well addressed and presents opportunity to exploit the target for disease management. © 2009 The Authors Journal compilation © 2010 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd.

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