Search tips
Search criteria

Results 1-4 (4)

Clipboard (0)

Select a Filter Below

more »
Year of Publication
Document Types
2.  Imperfect Duplicate Insertions Type of Mutations in Plasmepsin V Modulates Binding Properties of PEXEL Motifs of Export Proteins in Indian Plasmodium vivax 
PLoS ONE  2013;8(3):e60077.
Plasmepsin V (PM-V) have functionally conserved orthologues across the Plasmodium genus who's binding and antigenic processing at the PEXEL motifs for export about 200–300 essential proteins is important for the virulence and viability of the causative Plasmodium species. This study was undertaken to determine P. vivax plasmepsin V Ind (PvPM-V-Ind) PEXEL motif export pathway for pathogenicity-related proteins/antigens export thereby altering plasmodium exportome during erythrocytic stages.
We identify and characterize Plasmodium vivax plasmepsin-V-Ind (mutant) gene by cloning, sequence analysis, in silico bioinformatic protocols and structural modeling predictions based on docking studies on binding capacity with PEXEL motifs processing in terms of binding and accessibility of export proteins.
Cloning and sequence analysis for genetic diversity demonstrates PvPM-V-Ind (mutant) gene is highly conserved among all isolates from different geographical regions of India. Imperfect duplicate insertion types of mutations (SVSE from 246–249 AA and SLSE from 266–269 AA) were identified among all Indian isolates in comparison to P.vivax Sal-1 (PvPM-V-Sal 1) isolate. In silico bioinformatics interaction studies of PEXEL peptide and active enzyme reveal that PvPM-V-Ind (mutant) is only active in endoplasmic reticulum lumen and membrane embedding is essential for activation of plasmepsin V. Structural modeling predictions based on docking studies with PEXEL motif show significant variation in substrate protein binding of these imperfect mutations with data mined PEXEL sequences. The predicted variation in the docking score and interacting amino acids of PvPM-V-Ind (mutant) proteins with PEXEL and lopinavir suggests a modulation in the activity of PvPM-V in terms of binding and accessibility at these sites.
Our functional modeled validation of PvPM-V-Ind (mutant) imperfect duplicate insertions with data mined PEXEL sequences leading to altered binding and substrate accessibility of the enzyme makes it a plausible target to investigate export mechanisms for in silico virtual screening and novel pharmacophore designing.
PMCID: PMC3612065  PMID: 23555891
3.  Analysis of autosomal dominant spinocerebellar ataxia type 1 in an extended family of central India 
Indian Journal of Human Genetics  2012;18(3):299-304.
Spinocerebeller ataxia type 1 (SCA1) is a specific type of ataxia among a group of inherited diseases of the central nervous system. In SCA1, genetic defects lead to impairment of specific nerve fibers carrying messages to and from the brain, resulting in the degeneration of the cerebellum, the coordination center of the brain. We investigated 24 members of an extended family in Gwalior city, India, some of which were earlier clinically diagnosed to be suffering from yet unconfirmed type of SCA neurodegenerative disorder.
All the family members from each age group were screened clinically and the characteristics of those resembling with ataxia were recorded for diagnosis by MRI. The confirmed patients of the family were genetically tested by PCR based molecular testing to identify the type of SCA (i.e., SCA 1, 2, 3, 4, 6 or 7). Family tree of the disease inheritance was constructed by pedigree based method.
We found the clinical (symptoms and MRI) and genetic (Pedigree and PCR) results to be correlated. The PCR result revealed the disease to be of SCA 1 type being inherited in the family.
PMCID: PMC3656518  PMID: 23716937
Cerebellum; magnetic resonance imaging; polymerase chain reaction; pedigree; spinocerebeller ataxia
4.  Quantitative Assessment of Expression of Lactate Dehydrogenase and its Isoforms 3 and 4 may Serve as Useful Indicators of Progression of Gallbladder Cancer: A Pilot Study 
We have studied the expression of lactate dehydrogenase and its isoforms in gall bladder cancer, cholelithiasis and chronic cholecystitis. Quantitative and qualitative assays of lactate dehydrogenase and its various isoforms were carried out in the blood sera of patients and healthy controls along with parallel estimation of various liver function test enzymes. Statistical analysis was done using the software Graph Pad Prism. Significantly high expression of lactate dehydrogenase along with alkaline phosphatase and total bilirubin (P ≤ 0.05) was observed in all the three clinical conditions as compared to controls. LDH showed an increasing trend from stage I to stage IV of GBC indicating a significant positive association with the disease progression. The levels of LDH 3 and 4 isoforms appeared significantly more elevated in GBC than cholelithiasis or chronic cholecystitis. We suggest that a careful estimation of total LDH and its isoforms 3 and 4 alone or along with alkaline phosphatase and total bilirubin during different clinical stages, like chronic cholecystitis, cholelithiasis and GBC, may prove to be a potentially useful biomarker in the prognostic management of gall bladder diseases, specifically GBC.
PMCID: PMC3107415  PMID: 22468041
Gallbladder cancer; Lactate dehydrogenase; Cholelithiasis; Chronic cholecystitis

Results 1-4 (4)