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1.  MRS in Early and Presymptomatic Carriers of a Novel Octapeptide Repeat Insertion in the Prion Protein Gene 
To evaluate the proton MR spectroscopy (1H MRS) changes in carriers of a novel octapeptide repeat insertion in the Prion Protein Gene (PRNP) and family history of frontotemporal dementia with ataxia. Four at-risk mutation carriers and 13 controls were compared using single voxel, short TE, 1H MRS from the posterior cingulate gyrus. The mutation carriers had an increased choline/creatine, p=0.003 and increased myoinositol/creatine ratio, p=0.003. 1H MRS identified differences in markers of glial activity and choline metabolism in pre- and early symptomatic carriers of a novel PRNP gene octapeptide insertion. These findings expand the possible diagnostic utility of 1H MRS in familial prion disorders.
PMCID: PMC3480551  PMID: 22612156
MRS; MRI; familial prion disorders; frontotemporal dementia
2.  Lipotropes promote immunobiochemical plasticity and protect fish against low-dose pesticide-induced oxidative stress 
Cell Stress & Chaperones  2013;19(1):61-81.
An experiment was conducted to evaluate the role of different lipotropes in modulating immunity and biochemical plasticity under conditions of sublethal low-dose pesticide-induced stress in fish. Labeo rohita fish fingerlings were divided in two sets with one set of fish continuously exposed to low-dose endosulfan (1/10th of 96-h LC50) for 21 days, the other was unexposed, and both sets of fish were fed with practical diets supplemented with either 2 % lecithin, 0.5 % betaine, or 0.1 % choline and compared against unsupplemented diet. Low-dose endosulfan exposure had adverse effects (P < 0.05/P < 0.01) on hematological profile (erythrocyte count, hemoglobin, and hematocrit), serum protein (total protein, albumin, and globulin) and lipid profile (cholesterol and triglyceride), anti-oxidative status (ascorbic acid content of muscle, liver, brain, and kidney and activity of anti-oxidative enzymes: catalase and superoxide dismutase), neurotransmission (acetylcholinesterase activity in muscle and brain), immunological attributes (WBC count, albumin to globulin ratio, phagocytic activity, and serum cortisol), and metabolic plasticity as revealed from enzyme activities (muscle lactate dehydrogenase, liver and kidney glucose-6-phosphatase dehydrogenase-G6PDH activity). Dietary lipotropes prevented these effects completely or partially and the effects were lipotrope dependent. Kinetics (maximum velocity value Vmax, catalytic efficiency and Michaelis constant Km) of G6PDH enzyme from crude extracts of liver and kidney indicated inhibition due to endosulfan but lipotropes could protect enzyme and showed a stabilizing effect. The supplements also helped maintain integrity of histoarchitecture of the hepatocytes in endosulfan-exposed fish to a great extent. Feeding lipotropes to fish reared in endosulfan-free water also improved hematological and serum protein and lipid profiles and were immunostimulatory. In conclusion, dietary lipotropes, especially betaine and lecithin at the levels used, improve erythropoiesis, serum protein and lipid profile, anti-oxidant status, immunocompetence, neurotransmission, and protect the livers of L. rohita fingerlings even when continuously exposed to low-dose endosulfan.
PMCID: PMC3857435  PMID: 23666764
Lipotropes; Pesticide stress; Hematological profile; Serum protein and lipid profile; Anti-oxidant status; Immunocompetence; Acetylcholinesterase activity; Biochemical plasticity; G6PDH kinetics; Labeo rohita; Immunostimulants
3.  Lipotropes Protect against Pathogen-Aggravated Stress and Mortality in Low Dose Pesticide-Exposed Fish 
PLoS ONE  2014;9(4):e93499.
The decline of freshwater fish biodiversity corroborates the trends of unsustainable pesticide usage and increase of disease incidence in the last few decades. Little is known about the role of nonlethal exposure to pesticide, which is not uncommon, and concurrent infection of opportunistic pathogens in species decline. Moreover, preventative measures based on current knowledge of stress biology and an emerging role for epigenetic (especially methylation) dysregulation in toxicity in fish are lacking. We herein report the protective role of lipotropes/methyl donors (like choline, betaine and lecithin) in eliciting primary (endocrine), secondary (cellular and hemato-immunological and histoarchitectural changes) and tertiary (whole animal) stress responses including mortality (50%) in pesticide-exposed (nonlethal dose) and pathogen-challenged fish. The relative survival with betaine and lecithin was 10 and 20 percent higher. This proof of cause-and-effect relation and physiological basis under simulated controlled conditions indicate that sustained stress even due to nonlethal exposure to single pollutant enhances pathogenic infectivity in already nutritionally-stressed fish, which may be a driver for freshwater aquatic species decline in nature. Dietary lipotropes can be used as one of the tools in resurrecting the aquatic species decline.
PMCID: PMC3972094  PMID: 24690771
4.  The Effect of N-Alkyl Substituents on the Usability of Imidazolium Cation-Based Ionic Liquids in Microemulsion Systems: A Technical Note 
AAPS PharmSciTech  2013;14(2):551-557.
PMCID: PMC3666005  PMID: 23463260
drug delivery; hemolysis; imidazolium; ionic liquids; microemulsion
5.  Feedback about action performed can alter the sense of self-agency 
Sense of agency refers to the sense of authorship of an action and its outcome. Sense of agency is often explained through computational models of motor control (e.g., the comparator model). Previous studies using the comparator model have manipulated action-outcome contingency to understand its effect on the sense of agency. More recent studies have shown that cues related to outcome, priming outcome and priming action have an effect on agency attribution. However, relatively few studies have focused on the effect of recalibrating internal predictions on the sense of agency. This study aims to investigate how feedback about action can recalibrate prediction and modulates the sense of agency. While participants performed a Flanker task, we manipulated the feedback about the validity of the action performed, independent of their responses. When true feedback is given, the sense of agency would reflect congruency between the sensory outcome and the action performed. The results show an opposite effect on the sense of agency when false feedback was given. We propose that feedback about action performed can recalibrate the prediction of sensory outcome and thus alter the sense of agency.
PMCID: PMC3933776  PMID: 24611059
sense of agency; motor control; forward model; error monitoring mechanisms; Flanker task; error feedback; action intention
6.  Difficult mask ventilation due to a large oral tumour 
Indian Journal of Anaesthesia  2014;58(1):101-102.
PMCID: PMC3968642  PMID: 24700924
7.  Genomic architecture of HIV-1 infection: Current status & challenges 
Studies on host genomics have revealed the existence of identifiable HIV-1 specific protective factors among infected individuals who remain naturally resistant viraemia controllers with little or no evidence of virus replication. These factors are broadly grouped into those that are immune associated (MHC, chemokines, cytokines, CTLs and others), linked to viral entry (chemokine co-receptors and ligands), act as post-entry restriction elements (TRIM5a, APOBEC3) and those associated with viral replication (cytokines and others). These features have been identified through multiple experimental approaches ranging from candidate gene approaches, genome wide association studies (GWAS), expression analysis in conjunction with functional assays in humans to primate based models. Several studies have highlighted the individual and population level gross differences both in the viral clade sequences as well as host determined genetic associations. This review collates current information on studies involving major histocompatibility complex (MHC) as well as non MHC genes in the context of HIV-1 infection and AIDS involving varied ethnic groups. Special focus of the review is on the genetic studies carried out on the Indian population. Further challenges with regard to therapeutic interventions based on current knowledge have been discussed along with discussion on documented cases of stem cell therapy and very early highly active antiretroviral therapy (HAART) interventions.
PMCID: PMC3928698  PMID: 24434320
AIDS; chemokine; elite controllers; genes; HIV-1; HLA; restriction; viraemia
8.  Protocol optimization for enhanced production of pigments in Spirulina 
Spirulina has attracted special attention due to its importance as human foodstuff and natural colours with specific functional properties. These functional properties have been attributed to phycobilins, carotenoids, phenolics and unsaturated fatty acids. Present study was conducted under controlled phytotron conditions to identify the efficient strains of Spirulina in terms of pigment synthesis and to optimize their enhanced production. Methodology for enhanced production was standardized by varying specific environmental parameters (light intensity, temperature, carbon dioxide concentration, pH and NaCl level). Different strains of Spirulina depicted variability and environmental parameters showed distinct influence on pigments. Growth and pigment production was recorded to be most efficient under optimized conditions of light intensity (70 μmol m−2 s−1), temperature (30 °C), CO2 concentration (550 ppm and 750 ppm), pH (10.5) and NaCl level (2 g L−1).
PMCID: PMC3991003  PMID: 24764599
Mass production; Pigments; Spirulina
9.  Genetic Dissection of Yield and Its Component Traits Using High-Density Composite Map of Wheat Chromosome 3A: Bridging Gaps between QTLs and Underlying Genes 
PLoS ONE  2013;8(7):e70526.
Earlier we identified wheat (Triticum aestivum L.) chromosome 3A as a major determinant of grain yield and its component traits. In the present study, a high-density genetic linkage map of 81 chromosome 3A-specific markers was developed to increase the precision of previously identified yield component QTLs, and to map QTLs for biomass-related traits. Many of the previously identified QTLs for yield and its component traits were confirmed and were localized to narrower intervals. Four novel QTLs one each for shoot biomass (Xcfa2262-Xbcd366), total biomass (wPt2740-Xcfa2076), kernels/spike (KPS) (Xwmc664-Xbarc67), and Pseudocercosporella induced lodging (PsIL) were also detected. The major QTLs identified for grain yield (GY), KPS, grain volume weight (GVWT) and spikes per square meter (SPSM) respectively explained 23.2%, 24.2%, 20.5% and 20.2% of the phenotypic variation. Comparison of the genetic map with the integrated physical map allowed estimation of recombination frequency in the regions of interest and suggested that QTLs for grain yield detected in the marker intervals Xcdo549-Xbarc310 and Xpsp3047-Xbarc356 reside in the high-recombination regions, thus should be amenable to map-based cloning. On the other hand, QTLs for KPS and SPSM flanked by markers Xwmc664 and Xwmc489 mapped in the low-recombination region thus are not suitable for map-based cloning. Comparisons with the rice (Oryza sativa L.) genomic DNA sequence identified 11 candidate genes (CGs) for yield and yield related QTLs of which chromosomal location of two (CKX2 and GID2-like) was confirmed using wheat aneuploids. This study provides necessary information to perform high-resolution mapping for map-based cloning and for CG-based cloning of yield QTLs.
PMCID: PMC3722237  PMID: 23894667
10.  IgM-monoclonal gammopathy neuropathy and tremor: A first epidemiologic case control study 
Parkinsonism & related disorders  2012;18(6):748-752.
Small case series suggest tremor occurs frequently in IgM-monoclonal gammopathy of undetermined significance (IgM-MGUS) neuropathy. Epidemiologic study to confirm this association is lacking. Whether the neuropathy or another remote IgM-effect is causal remains unsettled.
Materials and methods
An IgM-MGUS neuropathy case cohort (n=207) was compared to age, gender, and neuropathy impairment score (NIS) matched, other-cause neuropathy controls (n=414). Tremor details were extracted from structured neurologic evaluation. All patients underwent nerve conductions.
Tremor occurrence was significantly higher in IgM-MGUS case cohort (29%) than in control cohort (9.2%) (p=0.001). In IgM-MGUS cases, tremor was associated with worse NIS (p=0.025) and demyelinating nerve conductions (p=0.020), but 11 of 60 (18%) IgM-MGUS cases with tremor had axonal neuropathy. In other-cause neuropathy controls, tremor was associated with axonal nerve conductions (p=0.03) but not with NIS severity (p=0.57). Tremor occurrence associated with older age in controls, (p=0.004) but not in IgM-MGUS cases (p=0.272). Most IgM-MGUS tremor cases (49/60) had a postural-kinetic tremor, 8 had rest tremor, 3 had mixed rest-action. Alternative causes of tremor was identified in 42% of IgM-MGUS cases, the most common type is inherited essential tremor 6/60 (p=0.04).
This first epidemiologic case-control study validates association between IgM-MGUS neuropathy and tremor. Among IgM-MGUS neuropathy cases, severity as well as type of neuropathy (demyelinating over axonal) correlated with tremor occurrence. IgM-MGUS paraproteinemia may increase tremor expression in persons recognized with common other risk factors for tremor.
PMCID: PMC3372617  PMID: 22475624
Tremor; Peripheral Neuropathy; IgM-MGUS
11.  Comment: Molar approach with backward, upward, right and posterior manoeuvre 
Indian Journal of Anaesthesia  2013;57(4):431-432.
PMCID: PMC3800354  PMID: 24163476
12.  Onosma L.: A review of phytochemistry and ethnopharmacology 
Pharmacognosy Reviews  2013;7(14):140-151.
The genus Onosma L. (Boraginaceae) includes about 150 species distributed world-wide in which only about 75 plants has been described for its morphology and less than 10 plants for their chemical constituents and clinical potential. The phytochemical reports of this genus revels that it comprise mainly aliphatic ketones, lipids, naphthazarins, alkaloids, phenolic compounds, naphthoquinones, flavones while most important are shikonins and onosmins. The plants are traditionally used as laxative, anthelmintic and for alexipharmic effects. The plants are also equally use in eye, blood diseases, bronchitis, abdominal pain, stangury, thirst, itch, lecoderma, fever, wounds, burns, piles and urinary calculi. The flowers of various plants are prescribed as stimulants, cardiotonic, in body swelling while leaves are used as purgative and in cutaneous eruptions. The roots are used for coloring food stuffs, oils and dying wool and in medicinal preparations. This review emphasizes the distribution, morphology, phytochemical constituents, ethnopharmacology, which may help in future research.
PMCID: PMC3841992  PMID: 24347922
Alkannin; hispidone; naphthoquinones; Ratanjot; shikonin
13.  Regulation of protumorigenic pathways by Insulin like growth factor binding protein2 and its association along with β-catenin in breast cancer lymph node metastasis 
Molecular Cancer  2013;12:63.
Insulin like growth factor binding proteins modulate the mitogenic and pro survival effects of IGF. Elevated expression of IGFBP2 is associated with progression of tumors that include prostate, ovarian, glioma among others. Though implicated in the progression of breast cancer, the molecular mechanisms involved in IGFBP2 actions are not well defined. This study investigates the molecular targets and biological pathways targeted by IGFBP2 in breast cancer.
Transcriptome analysis of breast tumor cells (BT474) with stable knockdown of IGFBP2 and breast tumors having differential expression of IGFBP2 by immunohistochemistry was performed using microarray. Differential gene expression was established using R-Bioconductor package. For validation, gene expression was determined by qPCR. Inhibitors of IGF1R and integrin pathway were utilized to study the mechanism of regulation of β-catenin. Immunohistochemical and immunocytochemical staining was performed on breast tumors and experimental cells, respectively for β-catenin and IGFBP2 expression.
Knockdown of IGFBP2 resulted in differential expression of 2067 up regulated and 2002 down regulated genes in breast cancer cells. Down regulated genes principally belong to cell cycle, DNA replication, repair, p53 signaling, oxidative phosphorylation, Wnt signaling. Whole genome expression analysis of breast tumors with or without IGFBP2 expression indicated changes in genes belonging to Focal adhesion, Map kinase and Wnt signaling pathways. Interestingly, IGFBP2 knockdown clones showed reduced expression of β- catenin compared to control cells which was restored upon IGFBP2 re-expression. The regulation of β-catenin by IGFBP2 was found to be IGF1R and integrin pathway dependent. Furthermore, IGFBP2 and β-catenin are co-ordinately overexpressed in breast tumors and correlate with lymph node metastasis.
This study highlights regulation of β-catenin by IGFBP2 in breast cancer cells and most importantly, combined expression of IGFBP2 and β-catenin is associated with lymph node metastasis of breast tumors.
PMCID: PMC3698021  PMID: 23767917
IGFBP2; Breast cancer; Wnt signaling; β-catenin; Integrin
14.  Ditosylate Salt of Itraconazole and Dissolution Enhancement Using Cyclodextrins 
AAPS PharmSciTech  2012;13(3):863-874.
Salt formation has been a promising approach for improving the solubility of poorly soluble acidic and basic drugs. The aim of the present study was to prepare the salt form of itraconazole (ITZ), a hydrophobic drug to improve the solubility and hence dissolution performance. Itraconazolium ditolenesulfonate salt (ITZDITOS) was synthesized from ITZ using acid addition reaction with p-toluenesulfonic acid. Salt characterization was performed using 1H NMR, mass spectrometry, Fourier transform infrared spectroscopy, differential scanning calorimetry, and X-ray diffraction. The particle size and morphology was studied using dynamic light scattering technique and scanning electron microscopy, respectively. The solubility of the salt in water and various pharmaceutical solvents was found multifold than ITZ. The dissolution study exhibited 5.5-fold greater percentage release value in 3 h of ITZDITOS (44.53%) as compared with ITZ (8.54%). Results of in vitro antifungal studies using broth microdilution technique indicate that ITZDITOS possessed similar antifungal profile as that of ITZ when tested against four fungal pathogens. Furthermore, the physical mixtures of ITZDITOS with two cyclodextrins, β-cyclodextrin (β-CD), and 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) were prepared in different molar ratios and were evaluated for in vitro release. It was observed that in only 30 min of dissolution study, about 74 and 81% of drug was released from 1:3 molar ratios of ITZDITOS with β-CD and ITZDITOS with HP-β-CD, respectively, which was distinctly higher than the drug released from ITZ commercial capsules (70%). The findings warrant further preclinical and clinical studies on ITZDITOS so that it can be established as an alternative to ITZ for developing oral formulations.
PMCID: PMC3429683  PMID: 22669594
antifungal; BCS class II; dissolution rate; insoluble; itraconazole
15.  Rupatadine 
In the title compound (systematic name: 8-chloro-11-{1-[(5-methyl­pyridin-3-yl)meth­yl]piperidin-4-yl­idene}-6,11-di­hydro-5H-benzo[5,6]cyclo­hepta­[1,2-b]pyridine), C26H26ClN3, the dihedral angle between the mean planes of the chloro­phenyl and cyclo­hepta­[1,2-b]pyridinyl rings fused to the cyclo­heptane ring is 56.6 (1)°. The mean planes of the cyclo­hepta­[1,2-b]pyridinyl and 5-methyl­pyridin-3-yl rings are twisted by 64.9 (4)°. The central piperizene group is in a slightly distorted chair configuration. A weak intra­molecular C—H⋯N inter­action is observed between the cyclo­hepta­[1,2-b]pyridinyl and piperidin-4-yl­idene moieties.
PMCID: PMC3685114  PMID: 23795133
16.  Activation of TGF-β Pathway by Areca Nut Constituents: A Possible Cause of Oral Submucous Fibrosis 
PLoS ONE  2012;7(12):e51806.
Oral submucous fibrosis (OSF) is a chronic inflammatory disease characterized by the accumulation of excess collagen, and areca nut chewing has been proposed as an important etiological factor for disease manifestation. Activation of transforming growth factor-β signaling has been postulated as the main causative event for increased collagen production in OSF. Oral epithelium plays important roles in OSF, and arecoline has been shown to induce TGF-β in epithelial cells. In an attempt to understand the role of areca nut constituents in the manifestation of OSF, we studied the global gene expression profile in epithelial cells (HaCaT) following treatment with areca nut water extract or TGF-β. Interestingly, 64% of the differentially regulated genes by areca nut water extract matches with the TGF-β induced gene expression profile. Out of these, expression of 57% of genes was compromised in the presence of ALK5 (TβRI) inhibitor and 7% were independently induced by areca nut, highlighting the importance of TGF-β in areca nut actions. Areca nut water extract treatment induced p-SMAD2 and TGF-β downstream targets in HaCaT cells but not in human gingival fibroblast cells (hGF), suggesting epithelial cells could be the source of TGF-β in promoting OSF. Water extract of areca nut consists of polyphenols and alkaloids. Both polyphenol and alkaloid fractions of areca nut were able to induce TGF-β signaling and its downstream targets. Also, SMAD-2 was phosphorylated following treatment of HaCaT cells by Catechin, Tannin and alkaloids namely Arecoline, Arecaidine and Guvacine. Moreover, both polyphenols and alkaloids induced TGF-β2 and THBS1 (activator of latent TGF-β) in HaCaT cells suggesting areca nut mediated activation of p-SMAD2 involves up-regulation and activation of TGF-β. These data suggest a major causative role for TGF-β that is induced by areca nut in OSF progression.
PMCID: PMC3526649  PMID: 23284772
17.  OA01.11. Toxicity study and testicular regeneration property of swarna vanga 
Ancient Science of Life  2012;32(Suppl 1):S11.
Swarna-Vanga (SV) is a famous Kupipakva metallic preparation, which are therapeutically used as rejuvenator, anti-diabetic, and for testicular regeneration (Spermatogenesis) etc since 18th century. It contains Parad (mercury-Hg), Vanga (tin-Sn) and Gandhaka (Sulphur-S) in major amounts and our ancient author use different proportion of mercury in SV with respect to tin. So, in present study an attempt has been made to evaluate testicular regeneration property of SV with its safety and efficacy on albino rats.
1. Pharmaceutical Study: Preparation of SV in different proportion of Sn:Hg as 1:1,1:1/2, 1:1/4, 1:1/6. 2. Experimental Study: a) Toxicity study of SV for short (14 days) and long(40 days) duration in different doses, b) Regeneration property of SV on induced CdCl2 (Cadmium Chloride) testicular germinal epithelium of albinorats.
SV is a metallic preparation which contains mercury, tin and sulphur in major amount and the best product of SV is made by half of the mercury with the tin. SV does not show any toxic effects on therapeutic dose (12.5-25 gm/body weight of albino rats) but show some toxic effects on higher dose in longer duration. The ability of SV in generation of testicular germinal epithelium is seen on partial damaged testis which is produced by inducing CdCl2.
1) The presence of mercury at least in half proportion to tin in is necessary in making the SV of good standards, 2) SV is not toxic in therapeutic dose and is slightly toxic on higher doses in long duration, 3) SV has the property to regenerate partially damaged testicular tissue.
PMCID: PMC3800863
18.  A new method for radiolabeling of human immunoglobulin-G and its biological evaluation 
Radiolabeled human Immunoglobulin-G (hIgG) has demonstrated its utility in inflammation and infection imaging. However, the present method of radiolabeling hIgG is time-consuming and complex.
To develop a simplified method of radiolabeling hIgG with technetium-99m (99mTc) via a nicotinyl hydrazine derivative (99mTc-HYNIC-hIgG) and its biological evaluation.
In vitro and in vivo studies showed that 99mTc-hIgG prepared by this method was fairly stable in physiological saline and human serum till 24 h. Only 4.3% degradation of the radiolabeled drug was seen till 24 h. Blood clearance pattern of the radiopharmaceutical exhibited biphasic exponential pattern. Biodistribution of 99mTc-HYNIC-hIgG in mice was observed up to 24 h. Significant accumulation of the radiotracer was found in liver (4.93 %), kidney (3.67%) and intestine (2.12 %) at 4 h interval by 24 h interval, it was reduced to 1.99%, 2.18% and 1.93 % respectively. Significant amount of radioactivity in liver, kidney and intestine suggest hepatobilliary as well as renal route of clearance for 99mTc-HYNIC-hIgG. The anterior whole body and spot scintigraphy images showed increased uptake of 99mTc-HYNIC-hIgG, with the area seen as a focal hot spot, indicating good localization of the radiolabeled hIgG at the site of infection.
The present findings indicate that 99mTc-HYNIC-hIgG holds great potential for the scintigraphy localization of inflammation. The shelf life of the developed kit, when stored at (–) 20°C was found to be at least 3 months.
PMCID: PMC3523523  PMID: 23248561
Human immunoglobulin-G; HYNIC; inflammation; radiolabeling; scintigraphy; technetium-99m
19.  Bacillus subtilis SepF Binds to the C-Terminus of FtsZ 
PLoS ONE  2012;7(8):e43293.
Bacterial cell division is mediated by a multi-protein machine known as the “divisome”, which assembles at the site of cell division. Formation of the divisome starts with the polymerization of the tubulin-like protein FtsZ into a ring, the Z-ring. Z-ring formation is under tight control to ensure bacteria divide at the right time and place. Several proteins bind to the Z-ring to mediate its membrane association and persistence throughout the division process. A conserved stretch of amino acids at the C-terminus of FtsZ appears to be involved in many interactions with other proteins. Here, we describe a novel pull-down assay to look for binding partners of the FtsZ C-terminus, using a HaloTag affinity tag fused to the C-terminal 69 amino acids of B. subtilis FtsZ. Using lysates of Escherichia coli overexpressing several B. subtilis cell division proteins as prey we show that the FtsZ C-terminus specifically pulls down SepF, but not EzrA or MinC, and that the interaction depends on a conserved 16 amino acid stretch at the extreme C-terminus. In a reverse pull-down SepF binds to full-length FtsZ but not to a FtsZΔC16 truncate or FtsZ with a mutation of a conserved proline in the C-terminus. We show that the FtsZ C-terminus is required for the formation of tubules from FtsZ polymers by SepF rings. An alanine-scan of the conserved 16 amino acid stretch shows that many mutations affect SepF binding. Combined with the observation that SepF also interacts with the C-terminus of E. coli FtsZ, which is not an in vivo binding partner, we propose that the secondary and tertiary structure of the FtsZ C-terminus, rather than specific amino acids, are recognized by SepF.
PMCID: PMC3418248  PMID: 22912848
20.  Characterization of Tarakeshwara Rasa: An Ayurvedic herbomineral formulation 
Ayu  2012;33(3):406-411.
Tarakeshwara Rasa (TR) is an Ayurvedic herbomineral compound formulation used in the intervention of Prameha vis-à-vis diabetes mellitus. The present study was executed to establish a fingerprint for this unique formulation, which can be adopted by the Ayurvedic pharmacies for drug standardization. TR is a formulation prepared by the trituration of four ingredients Abhraka Bhasma (AB), Loha Bhasma (LB), Vanga Bhasma (VB) and Rasa Sindhura (RS) in equal quantities with honey for one day. Each of the ingredients were prepared according to the norms of Ayurvedic classical texts and by employing Electric Muffle Furnace as heating device for incineration. To ensure the proper preparation of Bhasmas, standard tests (Bhasma Pariksha) were employed. After Bhasma complies these tests, TR was prepared and subjected for qualitative analysis, X-Ray Diffraction (XRD) and Scanning Electron Microscopy (SEM) studies. LB, AB, VB, RS and TR were also studied for free metal presence by employing phosphomolybdic acid. Chemical analysis of TR reveals that it contains Fe, Sn, Hg, Al, Mn, Ca and Mg. XRD study indicates that TR contains Fe2O3 (maghamite) in major phase and SnO2 (cassiterite), HgS, SiO2, HgO in minor phases. SEM study revealed that the compound is an agglomeration of particles. The particle size was in between 0.5 and 2 μ. Free metal detection by phosphomolybdic acid revealed the absence of free metals in the final Bhasmas. This is the first study establishing the characterization of Tarakeshwara Rasa.
PMCID: PMC3665084  PMID: 23723650
Bhasma; characterization; rasaushadhi; scanning electron microscopy; X-ray diffraction
21.  Clinical Characterization of a Kindred with a Novel Twelve Octapeptide Repeat Insertion in the Prion Protein Gene 
Archives of Neurology  2011;68(9):1165-1170.
To report the clinical, electroencephalographic, and neuroradiologic findings in a kindred with a novel insertion in the prion protein gene (PRNP).
Clinical description of a kindred.
Mayo Clinic Alzheimer’s Disease Research Center (Rochester).
Two pathologically-confirmed cases and their relatives.
Main outcome measures
Clinical features, electroencephalographic patterns, magnetic resonance imaging abnormalities, genetic analyses and neuropathological features.
The proband presented with clinical and neuroimaging features of atypical frontotemporal dementia (FTD) and ataxia. Generalized tonic-clonic seizures developed later in her course, and electroencephalography revealed spike and wave discharges but no periodic sharp wave complexes. Her affected sister and father also exhibited FTD-like features, and both experienced generalized tonic-clonic seizures and gait ataxia late in their course. Genetic analyses in the proband identified a novel defect in PRNP with one mutated allele carrying a 288 base pair insertion (BPI) consisting of 12 octapeptide repeats. Neuropathologic examination of the sister and proband revealed PrP-positive plaques and widespread tau-positive tangles.
This kindred has a unique combination of clinical and neuropathologic features associated with the largest BPI identified to date in PRNP, and underscores the need to consider familial prion disease in the differential diagnosis of a familial FTD-like syndrome.
PMCID: PMC3326586  PMID: 21911696
frontotemporal dementia; FTD; nonfluent aphasia; Gerstmann–Straüssler–Scheinker syndrome (GSS); Creutzfeldt-Jakob disease (CJD); prion; PRNP
22.  Gene Expression Signature of DMBA-Induced Hamster Buccal Pouch Carcinomas: Modulation by Chlorophyllin and Ellagic Acid 
PLoS ONE  2012;7(4):e34628.
Chlorophyllin (CHL), a water-soluble, semi-synthetic derivative of chlorophyll and ellagic acid (EA), a naturally occurring polyphenolic compound in berries, grapes, and nuts have been reported to exert anticancer effects in various human cancer cell lines and in animal tumour models. The present study was undertaken to examine the mechanism underlying chemoprevention and changes in gene expression pattern induced by dietary supplementation of chlorophyllin and ellagic acid in the 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis model by whole genome profiling using pangenomic microarrays. In hamsters painted with DMBA, the expression of 1,700 genes was found to be altered significantly relative to control. Dietary supplementation of chlorophyllin and ellagic acid modulated the expression profiles of 104 and 37 genes respectively. Microarray analysis also revealed changes in the expression of TGFβ receptors, NF-κB, cyclin D1, and matrix metalloproteinases (MMPs) that may play a crucial role in the transformation of the normal buccal pouch to a malignant phenotype. This gene expression signature was altered on treatment with chlorophyllin and ellagic acid. Our study has also revealed patterns of gene expression signature specific for chlorophyllin and ellagic acid exposure. Thus dietary chlorophyllin and ellagic acid that can reverse gene expression signature associated with carcinogenesis are novel candidates for cancer prevention and therapy.
PMCID: PMC3317635  PMID: 22485181
23.  Utility of saliva and hair follicles in donor selection for hematopoietic stem cell transplantation and chimerism monitoring 
Chimerism  2012;3(1):9-17.
Selection of an HLA identical donor is a critical pre-requisite for successful hematopoietic stem cell transplantation (HSCT). Most transplant centers utilize blood as the most common source of DNA for HLA testing. However, obtaining blood through phlebotomy is often challenging in patients with conditions like severe leucopenia or hemophilia, pediatric and elderly patients. We have used a simple in-house protocol and shown that HLA genotypes obtained on DNA extracted from saliva or hair are concordant with blood and hence can be used for selection of donors for HSCT or organ transplantation. Similarly, for post-HSCT chimerism monitoring, non-availability of pre-transplant DNA samples poses a major limitation of reference STR fingerprints. This study shows that DNA obtained post-HSCT from hair follicles can be used to generate pre-transplant patient specific fingerprints while the STR profiles obtained in saliva samples cannot as these display a mixed state of chimerism.
PMCID: PMC3370928  PMID: 22690267
chimerism; DNA; hair; HLA; saliva; transplantation
24.  Genomic Profiling Identifies Novel Mutations and SNPs in ABCD1 Gene: A Molecular, Biochemical and Clinical Analysis of X-ALD Cases in India 
PLoS ONE  2011;6(9):e25094.
X-linked adrenoleukodystrophy (X-ALD) affects the nervous system white matter and adrenal cortex secondary to mutations in the ABCD1 gene that encode the peroxisomal membrane protein. We conducted a genomic and protein expression study of susceptibility gene with its clinical and biochemical analysis. To the best of our knowledge this is the first preliminary comprehensive study in Indian population that identified novel mutations and SNPs in a relatively large group. We screened 17 Indian indigenous X-linked adrenoleukodystrophy cases and 70 controls for mutations and SNPs in the exonic regions (including flanking regions) of ABCD1 gene by direct sequencing with ABI automated sequencer along with Western blot analysis of its endogenous protein, ALDP, levels in peripheral blood mononuclear cells. Single germ line mutation was identified in each index case in ABCD1 gene. We detected 4 novel mutations (2 missense and 2 deletion/insertion) and 3 novel single nucleotide polymorphisms. We observed a variable protein expression in different patients. These findings were further extended to biochemical and clinical observations as it occurs with great clinical expression variability. This is the first major study in this population that presents a different molecular genetic spectrum as compared to Caucasian population due to geographical distributions of ethnicity of patients. It enhances our knowledge of the causative mutations of X-ALD that grants holistic base to develop effective medicine against X-ALD.
PMCID: PMC3178599  PMID: 21966424
25.  Chemical modification of L-glutamine to alpha-amino glutarimide on autoclaving facilitates Agrobacterium infection of host and non-host plants: A new use of a known compound 
BMC Chemical Biology  2011;11:1.
Accidental autoclaving of L-glutamine was found to facilitate the Agrobacterium infection of a non host plant like tea in an earlier study. In the present communication, we elucidate the structural changes in L-glutamine due to autoclaving and also confirm the role of heat transformed L-glutamine in Agrobacterium mediated genetic transformation of host/non host plants.
When autoclaved at 121°C and 15 psi for 20 or 40 min, L-glutamine was structurally modified into 5-oxo proline and 3-amino glutarimide (α-amino glutarimide), respectively. Of the two autoclaved products, only α-amino glutarimide facilitated Agrobacterium infection of a number of resistant to susceptible plants. However, the compound did not have any vir gene inducing property.
We report a one pot autoclave process for the synthesis of 5-oxo proline and α-amino glutarimide from L-glutamine. Xenobiotic detoxifying property of α-amino glutarimide is also proposed.
PMCID: PMC3130638  PMID: 21624145

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