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51.
Tanvir Khaliq Pragya Misra Swati Gupta K. Papi Reddy Ruchir Kant P.R. Maulik Anuradha Dube T. Narender 《Bioorganic & medicinal chemistry letters》2009,19(9):2585-2586
Protozoic infections caused by genus Leishmania pose an enormous public health threat in developing countries, compounded by the toxicity and resistance to current therapies. Under the aegis of our ongoing program on drug discovery and development on antileishmanial agents from plants, we carried out bioassay guided fractionation on Peganum harmala seeds which resulted in the isolation of 1 as an antileishmanial agent. 2D-NMR spectral data and single crystal X-ray crystallography data indicated 1 as peganine hydrochloride in dihydrated form. The compound 1 exhibited in-vitro activity against both extracellular promastigotes as well as intracellular amastigotes residing within murine macrophages in Leishmania donovani. Furthermore, 1 also exhibited in-vivo activity, 79.6 (±8.07)% against established VL in hamsters at a dose of 100 mg/kg b.wt. 相似文献
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53.
Sharma P Dube D Sinha M Mishra B Dey S Mal G Pathak KM Kaur P Sharma S Singh TP 《The Journal of biological chemistry》2011,286(36):31723-31730
The peptidoglycan recognition protein PGRP-S is an innate immunity molecule that specifically interacts with microbial peptidoglycans and other pathogen-associated molecular patterns. We report here two structures of the unique tetrameric camel PGRP-S (CPGRP-S) complexed with (i) muramyl dipeptide (MDP) at 2.5 Å resolution and (ii) GlcNAc and β-maltose at 1.7Å resolution. The binding studies carried out using surface plasmon resonance indicated that CPGRP-S binds to MDP with a dissociation constant of 10−7 m, whereas the binding affinities for GlcNAc and β-maltose separately are in the range of 10−4 m to 10−5 m, whereas the dissociation constant for the mixture of GlcNAc and maltose was estimated to be 10−6 m. The data from bacterial suspension culture experiments showed a significant inhibition of the growth of Staphylococcus aureus cells when CPGRP-S was added to culture medium. The ELISA experiment showed that the amount of MDP-induced production of TNF-α and IL-6 decreased considerably after the introduction of CPGRP-S. The crystal structure determinations of (i) a binary complex with MDP and (ii) a ternary complex with GlcNAc and β-maltose revealed that MDP, GlcNAc, and β-maltose bound to CPGRP-S in the ligand binding cleft, which is situated at the interface of molecules C and D of the homotetramer formed by four protein molecules A, B, C, and D. In the binary complex, the muramyl moiety of MDP is observed at the C-D interface, whereas the peptide chain protrudes into the center of tetramer. In the ternary complex, GlcNAc and β-maltose occupy distinct non-overlapping positions belonging to different subsites. 相似文献
54.
Parasitic plants are increasingly becoming the focus of research in many ecosystems. They have been shown to alter litterfall properties and decomposition rates in environments where they occur. Despite this recognition, the role of mistletoes in nutrient cycling in semi-arid savanna remains poorly understood. We investigated the litter input, element returns, and associated below-canopy soil nutrient concentrations of three mistletoe species (Erianthemum ngamicum, Plicosepalus kalachariensis, and Viscum verrucosum) that parasitize Acacia karroo trees in a semi-arid savanna, southwest Zimbabwe. Element concentrations in mistletoe leaf litter were enriched relative to the host. Litterfall from mistletoes significantly increased overall litterfall by up to 173 %, with E. ngamicum and P. kalachariensis having greater litterfall than their host trees. Associated with these changes in litterfall was an increase in element returns and the below-canopy soil nutrient concentrations. The increase in nutrient returns was due to both the effect of enriched mistletoe litter and increased volumes of litterfall beneath host trees. Litterfall, element returns, and the below-canopy soil nutrient concentrations were significantly influenced by mistletoe density, with higher values at high mistletoe density. Overall, E. ngamicum and P. kalachariensis had greater influence on litterfall, element returns, and soil nutrient concentrations than V. verrucosum. These findings are consistent with current understanding of enhanced nutrient cycling in the presence of parasitic plants particularly in nutrient-poor ecosystems. We conclude that the introduction of nutrients and associated increase in resource heterogeneity play an important role in determining ecosystem structure and function in semi-arid savannas. 相似文献
55.
Jorge L. Medina Jacqueline J. Coalson Edward G. Brooks Claude Jourdan Le Saux Vicki T. Winter Adriana Chaparro Molly F. R. Principe Laura Solis T. R. Kannan Joel B. Baseman Peter H. Dube 《PloS one》2014,9(7)
Mycoplasma pneumoniae causes a range of airway and extrapulmonary pathologies in humans. Clinically, M. pneumoniae is associated with acute exacerbations of human asthma and a worsening of experimentally induced asthma in mice. Recently, we demonstrated that Community Acquired Respiratory Distress Syndrome (CARDS) toxin, an ADP-ribosylating and vacuolating toxin synthesized by M. pneumoniae, is sufficient to induce an asthma-like disease in BALB/cJ mice. To test the potential of CARDS toxin to exacerbate preexisting asthma, we examined inflammatory responses to recombinant CARDS toxin in an ovalbumin (OVA) murine model of asthma. Differences in pulmonary inflammatory responses between treatment groups were analyzed by histology, cell differentials and changes in cytokine and chemokine concentrations. Additionally, assessments of airway hyperreactivity were evaluated through direct pulmonary function measurements. Analysis of histology revealed exaggerated cellular inflammation with a strong eosinophilic component in the CARDS toxin-treated group. Heightened T-helper type-2 inflammatory responses were evidenced by increased expression of IL-4, IL-13, CCL17 and CCL22 corresponding with increased airway hyperreactivity in the CARDS toxin-treated mice. These data demonstrate that CARDS toxin can be a causal factor in the worsening of experimental allergic asthma, highlighting the potential importance of CARDS toxin in the etiology and exacerbation of human asthma. 相似文献
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57.
M P Svetlova L M Perelygina Sh Dube N V Tomilin 《Molekuliarnaia genetika, mikrobiologiia i virusologiia》1988,(4):19-22
In nuclear extract of HeLa cells two proteins were identified having the specific binding activity to cloned 1.8kb fragment of human satellite DNA III (HS3). One of the satellite binding proteins (SBP1) purified by column chromatography using DEAE-, phospho- and DNA-cellulose steps interacted also with adenovirus 5 replication enhancer (ARE), another protein (SBP2) was separated during phosphocellulose chromatography from ARE-binding protein. It is suggested that SBP1 is possibly identical to the nuclear factor I purified earlier from the nuclear extract of HeLa cells by other authors. 相似文献
58.
G P Dube Y H Baik P L Vaghy A Schwartz 《Biochemical and biophysical research communications》1985,128(3):1295-1302
Bay k 8644 and nitrendipine, dihydropyridines classified as calcium channel agonist and antagonist, respectively, produced concentration-dependent biphasic responses (contraction and relaxation) in porcine coronary artery rings. Nitrendipine relaxed rings (IC50 = 60 nM) that were contracted with 100 nM Bay k 8644. Pretreatment of rings with 60 nM nitrendipine caused paradoxical potentiation of Bay k 8644-induced contraction. The data are consistent with a model that consists of two functionally-distinct dihydropyridine "receptors" with which Bay k 8644 and nitrendipine interact as partial agonists. We propose that these excitatory and inhibitory dihydropyridine receptor subtypes mediate contraction and relaxation, respectively, by dihydropyridines. 相似文献
59.
D K Dube J D Parker D C French D S Cahill S Dube M S Horwitz K M Munir L A Loeb 《Biochemistry》1991,30(51):11760-11767
We have obtained 42 active artificial mutants of HSV-1 thymidine kinase (ATP:thymidine 5'-phosphotransferase, EC 2.7.1.21) by replacing codons 166 and 167 with random nucleotide sequences. Codons 166 and 167 are within the putative nucleoside binding site in the HSV-1 tk gene. The spectrum of active mutations indicates that neither Ile166 nor Ala167 is absolutely required for thymidine kinase activity. Each of these amino acids can be replaced by some but not all of the 19 other amino acids. The active mutants can be classified as high activity or low activity on two bases: (1) growth of Escherichia coli KY895 (a strain lacking thymidine kinase activity) in the presence of thymidine and (2) uptake of thymidine by this strain, when harboring plasmids with the random insertions. E. coli KY895 harboring high-activity plasmids or wild-type plasmids can grow in the presence of low amounts of thymidine (less than 1 microgram/mL), but are unable to grow in the presence of high amounts of thymidine. On the other hand, E. coli KY895 harboring low-activity plasmids can grow at a high concentration of thymidine (greater than 50 microgram/mL) in the media. The high-activity plasmids also have an enhanced [3H]dT uptake. The amounts of thymidine kinase activity in vitro in unfractionated extracts do not correlate with either growth at low thymidine concentration or the rate of thymidine uptake. Heat inactivation studies indicate that the mutant enzymes are without exception more temperature-sensitive than the wild-type enzyme.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
60.
Germinal vesicle breakdown (GVBD) is the first visible response of the oocyte of Spisula solidissima to the neurohormone serotonin. Pharmacological characterization of this response was performed by using 24 serotonin-related compounds. Dose-response curves were assessed by quantification of GVBD. Rank orders of potency obtained were among agonists: serotonin greater than 8-hydroxy-2-(di-N-propylamino)tetralin hydrobromide greater than 2-methyl-serotonin greater than 1-(3-trifluoromethylphenyl)piperazine; among antagonists; ritanserin ritanserin greater than ICS205930 greater than mianserin = ketanserin = propranolol greater than metoclopramide = yohimbine greater than spiperone. Various other monoaminergic compounds tested were inefficient, demonstrating the specificity of the oocyte response to serotonin. Transduction mechanisms underlying this response were then investigated. Ca2+ appeared to be involved since serotonin induced an increase in the uptake of 45Ca2+ and since it was inefficient in calcium-free sea water. The absence of synergy between serotonin and KCl suggested that both compounds use a common transduction pathway. Exposure of the oocyte to the protein kinase C activator TPA inhibited serotonin-dependent maturation. Our data thus point to an original, previously uncharacterized pharmacological profile and transduction mechanism by which serotonin induces oocyte meiosis reinitiation in Spisula solidissima. 相似文献