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551.
Khunza Meraj Manoj Kumar Mahto N Blessy Christina Nidhi Desai Sajad Shahbazi Matcha Bhaskar 《Bioinformation》2012,8(23):1139-1146
The sodium “channelopathies” are the first among the ion channel diseases identified and have attracted widespread clinical and
scientific interests. Human voltage gated sodium channels are sites of action of several antiarrhythmic drugs, local anesthetics and
related antiepileptic drugs. The present study aims to optimize the activity of Disopyramide, by modification in its structures
which may improve the drug action by reducing its side effects. Herein, we have selected Human voltage-gated sodium channel
protein type 5 as a potent molecular target. Nearly eighty analogs of Disopyramide are designed and optimized. Thirty are selected
for energy minimization using Discovery studio and the LigPrep 2.5. Prior to docking, the active sites of all the proteins are
identified. The processing, optimization and minimization of all the proteins is done in Protein preparation wizard. The docking
study is performed using the GLIDE. Finally top five ranked lead molecules with better dock scores are identified as having strong
binding affinity to 2KAV protein than Disopyramide based on XP G scores. These five leads are further docked with other similar
voltage gated sodium channel proteins (PDB IDs: 2KBI, 4DCK, 2L53 and 4DJC) and the best scoring analog with each protein is
identified. Drug likeliness and comparative bioactivity analysis for all the analogs is done using QikProp 3.4. Results have shown
that the top five lead molecules would have the potential to act as better drugs as compared to Disopyramide and would be of
interest as promising starting point for designing compounds against various Sodium channelopathies. 相似文献
552.
553.
A study was undertaken to determine the rate of population expansion of an ischnoceran Phthiraptera, Goniocotes gallinae (infesting the domestic fowl, Gallus gallus domesticus), on the basis of in vitro and in vivo studies. Data obtained from in vitro rearing were utilized to construct the life history of the louse. The values of the gross reproductive rate (12.49 female eggs/female), net reproductive rate (8.31 female eggs/female), mean length of generation (36.91 days), precise generation time (35.65 days), finite rate of increase (1.06 female/days), and intrinsic rate of natural increase (0.059) of G. gallinae were determined. However, doubling-time values recorded during in vivo studies (14 days) was comparatively higher than those during in vitro rearing (11.73 days). 相似文献
554.
Nidhi Sharma Qianzheng Zhu Gulzar Wani Jingshan He Qi-En Wang Altaf A Wani 《Cell cycle (Georgetown, Tex.)》2014,13(1):106-114
Histone ubiquitination plays a vital role in DNA damage response (DDR), which is important for maintaining genomic integrity in eukaryotic cells. In DDR, ubiquitination of histone H2A and γH2AX by the concerted action of ubiquitin (Ub) ligases, RNF168 and RNF8, generates a cascade of ubiquitination signaling. However, little is known about deubiquitinating enzymes (DUBs) that may catalyze the removal of Ub from these histones. This study demonstrated that USP3, an apparent DUB for mono-ubiquitinated H2A, is indeed the enzyme for deubiquitinating Ub conjugates of γH2AX and H2A from lysine sites, where the ubiquitination is initiated by RNF168. Here, we showed that ectopic expression of USP3 led to the deubiquitination of both H2A and γH2AX in response to UV-induced DNA damage. Moreover, ectopic USP3 expression abrogated FK2 antibody-reactive Ub-conjugate foci, which co-localize with damage-induced γH2AX foci. In addition, USP3 overexpression impaired the accumulation of downstream repair factors BRCA1 and 53BP1 at the damage sites in response to both UV and γ-irradiation. We further identified that the USP3 removes Ub at lysine 13 and 15 of H2A and γH2AX, as well as lysine 118 and 119 of H2AX in response to DNA damage. Taken together, the results suggested that USP3 is a negative regulator of ubiquitination signaling, counteracting RNF168- and RNF8-mediated ubiquitination. 相似文献
555.
Michael Waisberg Alvaro Molina-Cruz Daniella M. Mizurini Nidhi Gera Beatriz C. Sousa Dongying Ma Ana C. Leal Tainá Gomes Michalis Kotsyfakis José M. C. Ribeiro Jan Lukszo Karine Reiter Stephen F. Porcella Carlo J. Oliveira Robson Q. Monteiro Carolina Barillas-Mury Susan K. Pierce Ivo M. B. Francischetti 《PLoS pathogens》2014,10(9)
Background
Invasion of mosquito salivary glands (SGs) by Plasmodium falciparum sporozoites is an essential step in the malaria life cycle. How infection modulates gene expression, and affects hematophagy remains unclear.Principal Findings
Using Affimetrix chip microarray, we found that at least 43 genes are differentially expressed in the glands of Plasmodium falciparum-infected Anopheles gambiae mosquitoes. Among the upregulated genes, one codes for Agaphelin, a 58-amino acid protein containing a single Kazal domain with a Leu in the P1 position. Agaphelin displays high homology to orthologs present in Aedes sp and Culex sp salivary glands, indicating an evolutionarily expanded family. Kinetics and surface plasmon resonance experiments determined that chemically synthesized Agaphelin behaves as a slow and tight inhibitor of neutrophil elastase (KD∼10 nM), but does not affect other enzymes, nor promotes vasodilation, or exhibit antimicrobial activity. TAXIscan chamber assay revealed that Agaphelin inhibits neutrophil chemotaxis toward fMLP, affecting several parameter associated with cell migration. In addition, Agaphelin reduces paw edema formation and accumulation of tissue myeloperoxidase triggered by injection of carrageenan in mice. Agaphelin also blocks elastase/cathepsin-mediated platelet aggregation, abrogates elastase-mediated cleavage of tissue factor pathway inhibitor, and attenuates neutrophil-induced coagulation. Notably, Agaphelin inhibits neutrophil extracellular traps (NETs) formation and prevents FeCl3-induced arterial thrombosis, without impairing hemostasis.Conclusions
Blockade of neutrophil elastase emerges as a novel antihemostatic mechanism in hematophagy; it also supports the notion that neutrophils and the innate immune response are targets for antithrombotic therapy. In addition, Agaphelin is the first antihemostatic whose expression is induced by Plasmodium sp infection. These results suggest that an important interplay takes place in parasite-vector-host interactions. 相似文献556.
Travis A. Dittmer Nidhi Sahni Nard Kubben David E. Hill Marc Vidal Rebecca C. Burgess Vassilis Roukos Tom Misteli 《Molecular biology of the cell》2014,25(9):1493-1510
Laminopathies are a collection of phenotypically diverse diseases that include muscular dystrophies, cardiomyopathies, lipodystrophies, and premature aging syndromes. Laminopathies are caused by >300 distinct mutations in the LMNA gene, which encodes the nuclear intermediate filament proteins lamin A and C, two major architectural elements of the mammalian cell nucleus. The genotype–phenotype relationship and the basis for the pronounced tissue specificity of laminopathies are poorly understood. Here we seek to identify on a global scale lamin A–binding partners whose interaction is affected by disease-relevant LMNA mutations. In a screen of a human genome–wide ORFeome library, we identified and validated 337 lamin A–binding proteins. Testing them against 89 known lamin A disease mutations identified 50 disease-associated interactors. Association of progerin, the lamin A isoform responsible for the premature aging disorder Hutchinson–Gilford progeria syndrome, with its partners was largely mediated by farnesylation. Mapping of the interaction sites on lamin A identified the immunoglobulin G (IgG)–like domain as an interaction hotspot and demonstrated that lamin A variants, which destabilize the Ig-like domain, affect protein–protein interactions more globally than mutations of surface residues. Analysis of a set of LMNA mutations in a single residue, which result in three phenotypically distinct diseases, identified disease-specific interactors. The results represent a systematic map of disease-relevant lamin A interactors and suggest loss of tissue-specific lamin A interactions as a mechanism for the tissue-specific appearance of laminopathic phenotypes. 相似文献
557.
558.
The extraction and carrier-facilitated transport of amino acids (leucine, valine and glycine) was studied through chloroform bulk liquid membrane system using a series of non-cyclic receptors such as diethylene glycol (1), diethylene glycol dimethyl ether (2), diethylene glycol dibutyl ether (3), diethylene glycol dibenzoate (4), triethylene glycol (5) and tetraethylene glycol (6). The amount of amino acid extracted and transported depends mainly upon the structure and the concentration of the receptors and also on the concentration of amino acid. The receptors 1 to 4, having small chain length and flexible end groups, formed stable complexes with amino acids, and the flexibility of receptors in different conformational forms was responsible for their carrier ability, while the receptors 5 and 6, having larger chain length showed poor carrier ability. Hydrophobicity of amino acids also play an important role in the extraction as well as transport process. 相似文献
559.
Batish DR Singh HP Setia N Kaur S Kohli RK 《Zeitschrift für Naturforschung. C, Journal of biosciences》2006,61(7-8):465-471
A total of 23 volatile constituents was identified and characterized by GC and GC-MS in the volatile essential oil extracted from intact (juvenile and adult) and fallen (senescent and leaf litter) leaves of lemon-scented eucalyptus (Eucalyptus citriodora Hook.). The leaves differed in their pigment, water and protein content, and C/N ratio. The oils were, in general, monoterpenoid in nature with 18 monoterpenes and 5 sesquiterpenes. However, a great variability in the amount of essential oils and their individual constituents was observed in different leaf tissues. The amount was maximum in the senescent leaves collected from the floor of the tree closely followed by that from juvenile leaves. In all, 19 constituents were identified in oil from juvenile and senescent leaves compared to 23 in adult leaves and 20 in leaf litter, respectively. Citronellal, a characteristic monoterpene of the oil reported hitherto was found to be more (77-78%) in the juvenile and senescent leaves compared to 48 and 54%, respectively, in the adult leaves and leaf litter. In the adult leaves, however, the content of citronellol--another important monoterpene-- was very high (21.9%) compared to other leaf types (7.8-12.2%). Essential oil and its two major monoterpenes viz. citronellal and citronellol were tested for their phytotoxicity against two weeds (Amaranthus viridis and Echinochloa crus-galli) and two crops (Triticum aestivum and Oryza sativa) under laboratory conditions. A difference in the phytotoxicity, measured in terms of seedling length and dry weight, of oil from different leaves and major monoterpenes was observed. Oil from adult leaves was found to be most phytotoxic although it occurs in smaller amount (on unit weight basis). The different toxicity of different oil types was due to the relative amount of individual monoterpenes present in the oil, their solubility and interactive action. The study concludes that oil from senescent and juvenile leaves being rich in citronellal could be used as commercial source of citronellal whereas that from adult leaves for weed management programmes as it was the most phytotoxic. 相似文献
560.
Olivarimbola Andrianoelina Hery Rakotondraoelina Lolona Ramamonjisoa Jean Maley Pascal Danthu Jean-Marc Bouvet 《Biodiversity and Conservation》2006,15(4):1109-1128
There is an urgent need to maintain and restore a broad genetic base for the management of Dalbergia monticola, a very economically important but endangered tree species in Madagascar. Random amplified polymorphism DNAs (RAPDs) and
chloroplast microsatellite markers were used to quantify the genetic variation and to analyse the geographic distribution
of diversity. Ten locations covering most of the natural range were sampled. Sixty-three RAPD polymorphic and 15 monomorphic
loci were obtained from 122 individuals. Genetic diversity was low and very close among populations and regions. The unrooted
neighbour-joining tree exhibited 4 groups, representing 6% (p = 0.000) of the total variation. The greater part of the variance, 81%, was observed within populations. A Mantel test suggested
that genetic distances between populations were weakly correlated with geographic distances (R = 0.46, p = 0.12). The three chloroplast microsatellite primers assayed on 100 individuals gave 13 chlorotypes. Most of the populations
showed 2 or 3 haplotypes. Haplotype diversity for the total population was equal to HeCp = 0.83 and ranged from 0.00 to 0.80 among the populations. The unrooted neighbour-joining tree exhibited 4 groups corresponding
to the four regions representing 80% (p = 0.0000) of the total variation. Genetic diversity varies with regions, the north and south being less variable. Chlorotype
distribution, the phylogenetic tree and historical information suggest that putative refugias in the centre-north region originating
from the early Holocene could explain the pattern of variation observed today. By combining the results obtained at nuclear
and organellar loci, a strategy of conservation based on evolutionarily significant units is proposed. 相似文献