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91.
Madhura Pradhan Charu Suri Sinjan Choudhary Pradeep Kumar Naik 《Journal of biomolecular structure & dynamics》2018,36(1):195-208
Beta-sitosterol (β-SITO), a phytosterol present in many edible vegetables, has been reported to possess antineoplastic properties and cancer treatment potential. We have shown previously that it binds at a unique site (the ‘SITO-site’) compared to the colchicine binding site at the interface of α- and β-tubulin. In this study, we investigated the anticancer efficacy of β-SITO against invasive breast carcinoma using MCF-7 cells. Since ‘isotypes’ of β-tubulin show tissue-specific expression and many are associated with cancer drug resistance, using computer-assisted docking and atomistic molecular dynamic simulations, we also examined its binding interactions to all known isotypes of β-tubulin in αβ-tubulin dimer. β-SITO inhibited MCF-7 cell viability by up to 50%, compared to vehicle-treated control cells. Indicating its antimetastatic potential, the phytosterol strongly inhibited cell migration. Immunofluorescence imaging of β-SITO-treated MCF-7 cells exhibited disruption of the microtubules and chromosome organization. Far-UV circular dichroism spectra indicated loss of helical stability in tubulin when bound to β-SITO. Docking and MD simulation studies, combined with MM-PBSA and MM-GBSA calculations revealed that β-SITO preferentially binds with specific β-tubulin isotypes (βII and βIII) in the αβ-tubulin dimer. Both these β-tubulin isotypes have been implicated in drug resistance against tubulin-targeted chemotherapeutics. Our data show the tubulin-targeted anticancer potential of β-SITO, and its potential clinical utility against βII and βIII isotype-overexpressing neoplasms. 相似文献
92.
Rabindranath Ray Kaushik Ray Chinmay K. Panda 《Molecular and cellular biochemistry》1997,177(1-2):79-88
The uridylic acid rich nuclear RNAs (U1-U6 snRNAs) are involved mainly in the processing of pre-mRNA and pre-rRNA. So, any control of cell growth through pre-mRNA/pre-rRNA processing may have some regulation through altered UsnRNAs metabolism. With this idea, attempts have been made to see how the metabolism of the six major UsnRNAs' changed during the normal process of cellular proliferation associated with differentiation from pluripotent/totipotent stem cells of early embryonic stage to much more differentiated state of different cell/tissue lineages in different tissues/organs during the fetal and neonatal stages of growth. It has been seen that the levels of the six major UsnRNAs were high in day 8 embryo when the cells were mainly pluripotent/totipotent in nature, and during the progression of embryonic development the levels of these UsnRNAs gradually decreased (35-65%) up to the midgestational period (day 13) with some exception, when the organogenesis has already been started. However in the fetal life, the levels of these UsnRNAs were maximum or comparable around 18 ± 2 days of gestation in comparison to that in day 8 embryo when the kinetics of the maturational status of the different organs were quite high. But, the levels of these UsnRNAs' became low during day 21 of fetal life or in day 0 of birth (perturation period) in all the tissues/organs except high UsnRNAs' level in spleen. In the neonatal life, around 3 ± 1 days of birth these UsnRNAs' levels again became maximum in all the tissues/organs (except in thymus) followed by decrease up to 5/6 days, and to become steady with slight increase within one to two weeks, when the kinetics of the organ maturation reached to a steady state. In case of thymus, the levels of the U3-U6 snRNAs were high on day 0 of birth followed by decrease in their level on day 1/2 and then increased to become steady within 2-4 weeks; whereas the U1 and U2 snRNAs' levels were high on day 3 of birth and the subsequent changes were similar to that in other tissues/organs.Thus the different UsnRNAs' metabolism in the perturation period and in the early stages of neonatal life has indicated the differential cellular functions in these two stages of development. These alterations in the metabolism of these UsnRNAs might be due to the differential changes in the rate of synthesis of these UsnRNAs and/or with their differential turnover rate in the different stages of development. Also, the differential variations of these UsnRNAs' levels have been observed among the different tissues/organs at the respective stages of development indicating the differences in the UsnRNAs' metabolism among the different cell/tissue lineages. Thus, it can be concluded that the metabolism of these UsnRNAs were developmentally regulated with some cell/tissue lineage variations, which might have some role in the developmentally regulated cellular process of proliferation and differentiation, through altered RNA splicing and processing. 相似文献
93.
Summary The influence of different depths of submergence (6±1 and 3±1 cm) and moisture tensions (0, 20, 60, 350, 500 and 1000 millibar)
of lateritic sandy loam soil on root porosity and growth parameters of rice, variety IR8 was studied at two different growth
phases under controlled greenhouse conditions. Best rice growth occurred at 3±1 cm submergence and it significantly reduced
with the increase of soil moisture tension. Unlike other growth parameters, root length increased as the soil moisture tension
was raised. The development of pore spaces in rice roots decreased significantly with the increase in soil moisture tension.
However, higher root porosity was observed under greater depths of submergence. Irrespective of soil water condition, the
number and dry weight of the root system showed significant positive correlation with root porosity. Oxygen diffusion rate
in soil, which increased with the increasing moisture tension, was significantly and inversely related with the porosity of
rice root.
Contribution from the Agricultural Engineering Department, Indian Institute of Technology, Kharagpur, West Bengal, India. 相似文献
94.
Madhumita A. Pradhan John A. Blackford Jr. Ballachanda N. Devaiah Petria S. Thompson Carson C. Chow Dinah S. Singer S. Stoney Simons Jr. 《The Journal of biological chemistry》2016,291(1):342-354
Most of the steps in, and many of the factors contributing to, glucocorticoid receptor (GR)-regulated gene induction are currently unknown. A competition assay, based on a validated chemical kinetic model of steroid hormone action, is now used to identify two new factors (BRD4 and negative elongation factor (NELF)-E) and to define their sites and mechanisms of action. BRD4 is a kinase involved in numerous initial steps of gene induction. Consistent with its complicated biochemistry, BRD4 is shown to alter both the maximal activity (Amax) and the steroid concentration required for half-maximal induction (EC50) of GR-mediated gene expression by acting at a minimum of three different kinetically defined steps. The action at two of these steps is dependent on BRD4 concentration, whereas the third step requires the association of BRD4 with P-TEFb. BRD4 is also found to bind to NELF-E, a component of the NELF complex. Unexpectedly, NELF-E modifies GR induction in a manner that is independent of the NELF complex. Several of the kinetically defined steps of BRD4 in this study are proposed to be related to its known biochemical actions. However, novel actions of BRD4 and of NELF-E in GR-controlled gene induction have been uncovered. The model-based competition assay is also unique in being able to order, for the first time, the sites of action of the various reaction components: GR < Cdk9 < BRD4 ≤ induced gene < NELF-E. This ability to order factor actions will assist efforts to reduce the side effects of steroid treatments. 相似文献
95.
T Katsuno T K Pradhan R R Ryan S A Mantey W Hou P J Donohue M A Akeson E R Spindel J F Battey D H Coy R T Jensen 《Biochemistry》1999,38(22):7307-7320
Recently, a fourth member of the bombesin (Bn) receptor family (fBB4-R) was isolated from a cDNA library from the brain of the frog, Bombina orientalis. Its pharmacology and cell biology are largely unknown, and no known natural cell lines or tissues possess sufficient numbers of fBB4-R's to allow either of these to be determined. To address these issues, we have used three different strategies. fBB4-R expression in cells widely used for other Bn receptor subtypes was unsuccessful as was expression in two frog cell lines. However, stable fBB4-R cell lines were obtained in CHO-K1 cells which were shown to faithfully demonstrate the correct pharmacology of the related Bn receptor, the GRP receptor, when expressed in these cells. [DPhe6,betaAla11,Phe13,Nle14]Bn(6-14) was found to have high affinity (Ki = 0.4 nM) for the fBB4 receptor and 125I-[DTyr6,betaala11,Phe13,Nle14]Bn(6-14) to be an excellent ligand for this receptor. The fBB4-R had a unique pharmacology for naturally occurring Bn-related agonists, with the presence of a penultimate phenylalanine being critical for high-affinity interaction. It also had a unique profile for six classes of Bn antagonists. The fBB4-R was coupled to phospholipase C with activation increasing [3H]inositol phosphates and mobilizing Ca2+ almost entirely from cellular sources. There was a close correlation between agonist the receptor occupation and the receptor activation. Three of the five classes of Bn receptor antagonists that interacted with higher affinity with the fBB4-R functioned as fBB4-R antagonists and two as partial agonists. fBB4-R activation stimulated increases in phospholipase D (PLD) over the same range of concentrations at which it activated phospholipase C. These results demonstrate that the fBB4 receptor has a unique pharmacology for agonists and antagonists and is coupled to phospholipase C and D. The availability of these cell lines, this novel ligand, and the identification of three classes of antagonists that can be used as lead compounds should facilitate the further investigation of the pharmacology and cell biology of the BB4 receptor. 相似文献
96.
A Bacolla S Pradhan R J Roberts R D Wells 《The Journal of biological chemistry》1999,274(46):33011-33019
Initial velocity determinations were conducted with human DNA (cytosine-5) methyltransferase (DNMT1) on unmethylated and hemimethylated DNA templates in order to assess the mechanism of the reaction. Initial velocity data with DNA and S-adenosylmethionine (AdoMet) as variable substrates and product inhibition studies with methylated DNA and S-adenosylhomocysteine (AdoHcy) were obtained and evaluated as double-reciprocal plots. These relationships were linear for plasmid DNA, exon-1 from the imprinted small nuclear ribonucleoprotein-associated polypeptide N, (CGG.CCG)(12), (m(5)CGG. CCG)(12), and (CGG.CCG)(73) but were not linear for (CGG. Cm(5)CG)(12). Inhibition by AdoHcy was apparently competitive versus AdoMet and uncompetitive/noncompetitive versus DNA at =20 microM AdoMet. Addition of the product (methylated DNA) to unmethylated plasmid DNA increased V(max(app)) resulting in mixed stimulation and inhibition. Velocity equations indicated a two-step mechanism as follows: first, activation of DNMT1 by methylated DNA that bound to an allosteric site, and second, the addition of AdoMet and DNA to the catalytic site. The preference of DNMT1 for hemimethylated DNA may be the result of positive cooperativity of AdoMet binding mediated by allosteric activation by the methylated CG steps. We propose that this activation plays a role in vivo in the regulation of maintenance methylation. 相似文献
97.
TiD is a standalone application, which relies on basic assumption that a protein must be essential for pathogens survival and non-homologous with host to qualify as putative target. With an input bacterial proteome, TiD removes paralogous proteins, picks essential ones, and excludes proteins homologous with host organisms. The targets illustrate non-homology with at least 40 out of 84 gut microbes, considered safe for human. TiD classifies proposed targets as known, novel and virulent. Users can perform pathway analysis, choke point analysis, interactome analysis, subcellular localization and functional annotations through web servers cross-referenced with the application. Drug targets identified by TiD for Listeria monocytogenes, Bacillus anthracis and Pseudomonas aeruginosa have revealed significant overlaps with previous studies. TiD takes < 2 h to scan putative targets from a bacterial proteome with ~ 5000 proteins; hence, we propose it as a useful tool for rational drug design. TiD is available at http://bmicnip.in/TiD/. 相似文献
98.
Namrata Dhaka Kadambini Rout Satish K. Yadava Yaspal Singh Sodhi Vibha Gupta Deepak Pental Akshay K. Pradhan 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2017,130(2):293-307
Key message
Seed weight QTL identified in different populations were synthesized into consensus QTL which were shown to harbor candidate genes by in silico mapping. Allelic variation inferred would be useful in breeding B. juncea lines with high seed weight.Abstract
Seed weight is an important yield influencing trait in oilseed Brassicas and is a multigenic trait. Among the oilseed Brassicas, Brassica juncea harbors the maximum phenotypic variation wherein thousand seed weight varies from around 2.0 g to more than 7.0 g. In this study, we have undertaken quantitative trait locus/quantitative trait loci (QTL) analysis of seed weight in B. juncea using four bi-parental doubled-haploid populations. These four populations were derived from six lines (three Indian and three east European lines) with parental phenotypic values for thousand seed weight ranging from 2.0 to 7.6 g in different environments. Multi-environment QTL analysis of the four populations identified a total of 65 QTL ranging from 10 to 25 in each population. Meta-analysis of these component QTL of the four populations identified six ‘consensus’ QTL (C-QTL) in A3, A7, A10 and B3 by merging 33 of the 65 component Tsw QTL from different bi-parental populations. Allelic diversity analysis of these six C-QTL showed that Indian lines, Pusajaikisan and Varuna, hold the most positive allele in all the six C-QTL. In silico mapping of candidate genes with the consensus QTL localized 11 genes known to influence seed weight in Arabidopsis thaliana and also showed conserved crucifer blocks harboring seed weight QTL between the A subgenomes of B. juncea and B. rapa. These findings pave the way for a better understanding of the genetics of seed weight in the oilseed crop B. juncea and reveal the scope available for improvement of seed weight through marker-assisted breeding.99.
100.