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71.
Background
The Drosophila Male Specific Lethal (MSL) complex contains chromatin modifying enzymes and non-coding roX RNA. It paints the male X at hundreds of bands where it acetylates histone H4 at lysine 16. This epigenetic mark increases expression from the single male X chromosome approximately twofold above what gene-specific factors produce from each female X chromosome. This equalises X-linked gene expression between the sexes. Previous screens for components of dosage compensation relied on a distinctive male-specific lethal phenotype. 相似文献72.
Jaya Prabhakaran Vattoly J. Majo Matthew S. Milak Pratap Mali Lyudmila Savenkova J. John Mann Ramin V. Parsey J.S. Dileep Kumar 《Bioorganic & medicinal chemistry letters》2010,20(12):3654-3657
Radiosynthesis and in vivo evaluation of [N-methyl-11C] 5-methyl-3-[4-(3-phenylallyl)-piperazin-1-ylmethyl]-3,3a,4,5-tetrahydroisoxazolo[4,3-c]quinoline (1), a potential PET tracer for alpha2-adrenergic receptors is described. Syntheses of nonradioactive standard 1 and corresponding desmethyl precursor 2 were achieved from 2-aminobenzaldehyde in 40% and 65% yields, respectively. Methylation using [11C]CH3I in presence of aqueous potassium hydroxide in DMSO afforded [11C]1 in 25% yield (EOS) with >99% chemical and radiochemical purities with a specific activity ranged from 3–4 Ci/μmol (n = 6). The total synthesis time was 30 min from EOB. PET studies in anesthetized baboon show that [11C]1 penetrates BBB and accumulates in alpha2A-AR enriched brain areas. 相似文献
73.
Raghupathy Anchala Emanuele Di Angelantonio Dorairaj Prabhakaran Oscar H. Franco 《PloS one》2013,8(11)
Background
Hypertension remains the top global cause of disease burden. Decision support systems (DSS) could provide an adequate and cost-effective means to improve the management of hypertension at a primary health care (PHC) level in a developing country, nevertheless evidence on this regard is rather limited.Methods
Development of DSS software was based on an algorithmic approach for (a) evaluation of a hypertensive patient, (b) risk stratification (c) drug management and (d) lifestyle interventions, based on Indian guidelines for hypertension II (2007). The beta testing of DSS software involved a feedback from the end users of the system on the contents of the user interface. Software validation and piloting was done in field, wherein the virtual recommendations and advice given by the DSS were compared with two independent experts (government doctors from the non-participating PHC centers).Results
The overall percent agreement between the DSS and independent experts among 60 hypertensives on drug management was 85% (95% CI: 83.61 - 85.25). The kappa statistic for overall agreement for drug management was 0.659 (95% CI: 0.457 - 0.862) indicating a substantial degree of agreement beyond chance at an alpha fixed at 0.05 with 80% power. Receiver operator curve (ROC) showed a good accuracy for the DSS, wherein, the area under curve (AUC) was 0.848 (95% CI: 0.741 - 0.948). Sensitivity and specificity of the DSS were 83.33 and 85.71% respectively when compared with independent experts.Conclusion
A point of care, pilot tested and validated DSS for management of hypertension has been developed in a resource constrained low and middle income setting and could contribute to improved management of hypertension at a primary health care level. 相似文献74.
Seetharama D. S. Jois Latha M. Nagarajarao M. Prabhakaran A. Balasubramaniam 《Journal of biomolecular structure & dynamics》2013,31(1):497-508
Abstract Neuropeptide Y (NPY), receptors belong to the G-protein coupled receptor superfamily. NPY mediates several physiological responses, such as blood pressure, food intake, sedation. These actions of NPY are mediated by six receptor subtypes denoted as Y1-Y5 and y6. Modeling of receptor subtypes and binding site identification is an important step in developing new therapeutic agents. We have attempted to model the three NPY receptor types, Y1, Y4, and Y5 using homology modeling and threading methods. The models are consistent with previously reported experimental evidence. To understand the interaction and selectivity of NPY analogues with different neuropeptide receptors, docking studies of two neuropeptide analogues (BVD10 and BVD15) with receptors Y1 and Y4 were carried out. Results of the docking studies indicated that the interaction of ligands BVD10 and BVD15 with Y1 and Y4 receptors are different. These results were evaluated for selectivity of peptide analogues BVD10 and BVD15 towards the receptors. 相似文献
75.
Quorum quenching (QQ) is an effective approach for the prevention of bacterial infections involving biofilms. This study reports the QQ and anti-biofilm activities of a rhizospheric bacterium identified as Stenotrophomonas maltophilia BJ01. The QQ activity was demonstrated using Chromobacterium violaceum CV026 as a biosensor. A maximum of 95% reduction in violacein production, a quorum sensing-regulated behavior, was observed. Gas chromatography–mass spectroscopy of the extract showed that the active compound was cis-9-octadecenoic acid, which was confirmed by electronspray ionization–mass spectroscopy data. The extract also inhibited biofilm formation of Pseudomonas aeruginosa ATCC 9027 without affecting its growth. Scanning electron and atomic force microscopy showed architectural disruption of the biofilm when treated with the extract. This is the first report of the QQ and anti-biofilm activities of cis-9-octadecenoic acid isolated from any bacterium. It may have the potential to combat detrimental infections with P. aeruginosa. Further validation is required for any possible medical application. 相似文献
76.
R. Prabhakaran P. Kalaivani P. Poornima F. Dallemer R Huang V. Vijaya Padma K. Natarajan 《Bioorganic & medicinal chemistry》2013,21(21):6742-6752
A series of four new thiosemicarbazone complexes of palladium have been synthesized, characterized and evaluated for their DNA/protein binding with CT-DNA and BSA, respectively. The new complexes bound to CT-DNA by intercalation mode and in protein binding studies, the complexes bound to BSA binding mechanism was found as static quenching. Among them the complex 4 had a strong binding affinity with BSA. In addition, in vitro cytotoxic studies were carried out on lung cancer (A549) and liver cancer (HepG2) cell lines and found that the complexes exhibited better activity than their parent thiosemicarbazone analogues. The complex 3 exhibited better activity than other complexes and this fact supported by the increased accumulation of the complexes in to the cancer cells which are evident from inter cellular uptake studies. 相似文献
77.
Liu F Majo VJ Prabhakaran J Castrillion J Mann JJ Martinez D Kumar JS 《Bioorganic & medicinal chemistry letters》2012,22(6):2172-2174
Radiosynthesis of [N-methyl-(11)C](S)-N-([1,1'-biphenyl]-2-yl)-1-(2-((1-methyl-1H-benzo[d]imidazol-2-yl)thio)acetyl)pyrrolidine-2-carboxamide ([(11)C]BBAC or [(11)C]3) and [N-methyl-(11)C] (S)-N-([1,1'-biphenyl]-2-yl)-1-(3-(1-methyl-1H-benzo[d]imidazol-2-yl)propanoyl)pyrrolidine-2-carboxamide ([(11)C]BBPC or [(11)C]-4), two potential PET tracers for orexin2 receptors are described. Syntheses of non-radioactive standards 3, 4 and corresponding desmethyl precursors 1, 2 were achieved from common intermediate (S)-2-([1,1'-biphenyl]-2-yl)-1-(pyrrolidin-2-yl)ethanone. Methylation using [(11)C]CH(3)OTf in the presence of base in acetone afforded [(11)C]3 and [(11)C]4 in 30±5% yield (EOS) with >99 % radiochemical purities with a specific activity ranged from 2.5±0.5 Ci/μmol (EOB). The logP of [(11)C]3 and [(11)C]4 were determined as 3.4 and 2.8, respectively. The total synthesis time was 30 min from EOB. However, PET scans performed in a rhesus monkey did not show tracer retention or appropriate brain uptake. Hence [(11)C]3 and [(11)C]4 cannot be used as PET tracers for imaging orexin2 receptors. 相似文献
78.
Laura Kelly Shivani A. Patel K. M. Venkat Narayan Dorairaj Prabhakaran Solveig A. Cunningham 《PloS one》2014,9(8)
Social networks are believed to affect health-related behaviors and health. Data to examine the links between social relationships and health in low- and middle-income country settings are limited. We provide guidance for introducing an instrument to collect social network data as part of epidemiological surveys, drawing on experience in urban India. We describe development and fielding of an instrument to collect social network information relevant to health behaviors among adults participating in a large, population-based study of non-communicable diseases in Delhi, India. We discuss basic characteristics of social networks relevant to health including network size, health behaviors of network partners (i.e., network exposures), network homogeneity, network diversity, strength of ties, and multiplexity. Data on these characteristics can be collected using a short instrument of 11 items asked about up to 5 network members and 3 items about the network generally, administered in approximately 20 minutes. We found high willingness to respond to questions about social networks (97% response). Respondents identified an average of 3.8 network members, most often relatives (80% of network ties), particularly blood relationships. Ninety-one percent of respondents reported that their primary contacts for discussing health concerns were relatives. Among all listed ties, 91% of most frequent snack partners and 64% of exercise partners in the last two weeks were relatives. These results demonstrate that family relationships are the crux of social networks in some settings, including among adults in urban India. Collecting basic information about social networks can be feasibly and effectively done within ongoing epidemiological studies. 相似文献
79.
Kalaivani P Prabhakaran R Dallemer F Poornima P Vaishnavi E Ramachandran E Padma VV Renganathan R Natarajan K 《Metallomics : integrated biometal science》2012,4(1):101-113
The coordination propensities of 4(N,N')-diethylaminosalicylaldehyde-4(N)-substituted thiosemicarbazones (H(2)L(1-4)) were investigated by reacting with an equimolar amount of [PdCl(2)(PPh(3))(2)]. The new complexes were characterized by various spectroscopic techniques. The structure determination of the complexes [Pd(DeaSal-tsc)(PPh(3))] (1), [Pd(DeaSal-mtsc)(PPh(3))] (2) and [Pd(DeaSal-etsc)(PPh(3))] (3) by X-ray crystallography showed that ligands are coordinated in a dibasic tridentate ONS donor fashion forming stable five and six membered chelate rings. The binding ability of complexes (1-4) to calf-thymus DNA (CT DNA) has been explored by absorption and emission titration methods. Based on the observations, an electrostatic and an intercalative binding mode have been proposed. The protein binding studies have been monitored by quenching of tryptophan and tyrosine residues in the presence of complexes using lysozyme as a model protein. As determined by MTT assays, complex 3 exhibited a higher cytotoxic effect towards human lung cancer cell line (A549) and liver cancer cells (HepG2). LDH, NO assay and cellular uptake of the complexes have been studied. Further, antibacterial activity studies of the complexes have been screened against the pathogenic bacteria such as Enterococcus faecalis, Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa, MIC50 values of the complexes showed that the complexes exhibited significant activity against the pathogens and among the complexes, 3 exhibited higher activity. 相似文献
80.
Moore SC Gunter MJ Daniel CR Reddy KS George PS Yurgalevitch S Devasenapathy N Ramakrishnan L Chatterjee N Chanock SJ Berndt SI Mathew A Prabhakaran D Sinha R 《Obesity (Silver Spring, Md.)》2012,20(9):1902-1908
Recent studies have identified common genetic variants that are unequivocally associated with central adiposity, BMI, and/or fasting plasma glucose among individuals of European descent. Our objective was to evaluate these associations in a population of Asian-Indians. We examined 16 single-nucleotide polymorphisms (SNPs) from loci previously linked to waist circumference, BMI, or fasting glucose in 1,129 Asian-Indians from New Delhi and Trivandrum. Trained medical staff measured waist circumference, height, and weight. Fasting plasma glucose was measured from collected blood specimens. Genotype-phenotype associations were evaluated using linear regression, with adjustments for age, gender, religion, and study region. For gene-environment interaction tests, total physical activity (PA) during the past 7 days was assessed by the International Physical Activity Questionnaire (IPAQ). The T allele at the FTO rs3751812 locus was associated with increased waist circumference (per allele effect of +1.58 cm, P(trend) = 0.0015) after Bonferroni adjustment for multiple testing (P(adj) = 0.04). We also found a nominally statistically significant FTO-PA interaction (P(interaction) = 0.008). Among participants with <81 metabolic equivalent (MET)-h/wk of PA, the rs3751812 variant was associated with increased waist size (+2.68 cm; 95% confidence interval (CI) = 1.24, 4.12), but not among those with 212+ MET-h/wk (-1.79 cm; 95% CI = -4.17, 0.58). No other variant had statistically significant associations, although statistical power was modest. In conclusion, we confirmed that an FTO variant associated with central adiposity in European populations is associated with central adiposity among Asian-Indians and corroborated prior reports indicating that high PA attenuates FTO-related genetic susceptibility to adiposity. 相似文献