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191.
Strategic genome-scale prioritization of unique drug targets: A case study of Streptococcus gordonii
Sandeep Telkar Hulikal shivashankara Santosh Kumar Nagaraja Deeplanaik Riaz Mahmood 《Bioinformation》2013,9(19):983-987
The current reach of genomics extends facilitated identification of microbial virulence factors, a primary objective for antimicrobial
drug and vaccine design. Many putative proteins are yet to be identified which can act as potent drug targets. There is lack and
limitation of methods which appropriately combine several omics ways for putative and new drug target identification. The study
emphasizes a combined bioinformatic and theoretical method of screening unique and putative drug targets, lacking similarity
with experimentally reported essential genes and drug targets. Synteny based comparison was carried out with 11 streptococci
considering S. gordonii as reference genome. It revealed 534 non-homologous genes of which 334 were putative. Similarity search
against host proteome, metabolic pathway annotation and subcellular localization predication identified 16 potent drug targets.
This is a first attempt of several combinational approaches of similarity search with target protein structural features for screening
drug targets, yielding a pipeline which can be substantiated to other human pathogens. 相似文献
192.
SUMMARY
Restriction-modification (R-M) systems are ubiquitous and are often considered primitive immune systems in bacteria. Their diversity and prevalence across the prokaryotic kingdom are an indication of their success as a defense mechanism against invading genomes. However, their cellular defense function does not adequately explain the basis for their immaculate specificity in sequence recognition and nonuniform distribution, ranging from none to too many, in diverse species. The present review deals with new developments which provide insights into the roles of these enzymes in other aspects of cellular function. In this review, emphasis is placed on novel hypotheses and various findings that have not yet been dealt with in a critical review. Emerging studies indicate their role in various cellular processes other than host defense, virulence, and even controlling the rate of evolution of the organism. We also discuss how R-M systems could have successfully evolved and be involved in additional cellular portfolios, thereby increasing the relative fitness of their hosts in the population. 相似文献193.
Although microdamage is known to accumulate in trabecular bone with overloading and aging, the tissue-level stresses and strains associated with local bone failure are not well known. Local correlation of microdamage with microstructural stresses and strains requires methods to accurately register histological sections with micro-computed tomography (micro-CT) based finite element models. In addition, the resolution of correlation (i.e., grid size) selected for analysis may affect the observed results. Therefore, an automated, repeatable, and accurate image registration algorithm was developed to determine the range of local stresses and strains associated with microdamage initiation. Using a two-dimensional rigid registration algorithm, bone structures from histology and micro-CT imaging were aligned. Once aligned, microdamaged regions were spatially correlated with local stresses and strains obtained from micro-CT based finite element analysis. Using this more sophisticated registration technique, we were able to analyze the effects of varying spatial grid resolution on local stresses and strains initiating microdamage. The results indicated that grid refinement to the individual pixel level (pixel-by-pixel method) more precisely defined the range of microdamage initiation compared to manually selected individual damaged and undamaged trabeculae. Using the pixel-by-pixel method, we confirmed that trabecular bone from younger cows sustained higher local strains prior to microdamage initiation compared to older bone. 相似文献
194.
Gamma glutamyl transferases (GGT) are highly conserved enzymes that occur from bacteria to humans. They remove terminal y-glutamyl residue from peptides and amides. GGTs play an important role in the homeostasis of glutathione (a major cellular antioxidant) and in the detoxification of xenobiotics in mammals. They are implicated in diseases like diabetes, inflammation, neurodegenerative diseases and cardiovascular diseases. The physiological role of GGTs in bacteria is still unclear. Nothing is known about the basis for the strong conservation of the enzyme across the living system. The review focuses on the enzyme's physiology, chemistry and structural properties of the enzyme with emphasis on the evolutionary relationships. The available data indicate that the members of the GGT family share common structural features but are functionally heterogenous. 相似文献
195.
Sasikala M Surya P Radhika G Kumar PP Rao MS Mukherjee RM Rao PN Reddy DN 《World journal of stem cells》2011,3(7):63-69
AIM:To identify circulating CD90 + CD73 + CD45 cells and evaluate their in vitro proliferating abilities.METHODS:Patients with cirrhosis(n=43),and healthy volunteers(n=40)were recruited to the study.Mononuclear cells were isolated and cultured from the peripheral blood of controls and cirrhosis patients.Fibroblast-like cells that appeared in cultures were analyzed for morphological features,enumerated by flow cytometry and confirmed by immunocytochemistry(ICC).Colony forming efficiency(CFE)of these cells was assessed and expressed as a percentage.RESULTS:In comparison to healthy volunteers,cells obtained from cirrhotic patients showed a significantincrease(P<0.001)in the percentage of CD90+CD73+ CD45 cells in culture.Cultured cells also showed 10 fold increases in CFE.Flow cytometry and ICC confirmed that the proliferating cells expressed CD90 + CD73 + in the cultures from cirrhosis patients.CONCLUSION:These results indicate the presence of circulating CD90 + CD73 + CD45 cells in patients with liver cirrhosis that have the potential to proliferate at a higher rate. 相似文献
196.
Haloperidol is an antipsychotic drug that exerts its' antipsychotic effects by inhibiting dopaminergic neurons. Although the exact pathophysiology of haloperidol extrapyramidal symptoms are not known, the role of reactive oxygen species in inducing oxidative stress has been proposed as one of the mechanisms of prolonged haloperidol-induced neurotoxicity. In the present study, we evaluate the protective effect of alpha lipoic acid against haloperidol-induced oxidative stress in the rat brain. Sprague Dawley rats were divided into control, alpha lipoic acid alone (100 mg/kg p.o for 21 days), haloperidol alone (2 mg/kg i.p for 21 days), and haloperidol with alpha lipoic acid groups (for 21 days). Haloperidol treatment significantly decreased levels of the brain antioxidant enzymes super oxide dismutase and glutathione peroxidase and concurrent treatment with alpha lipoic acid significantly reversed the oxidative effects of haloperidol. Histopathological changes revealed significant haloperidol-induced damage in the cerebral cortex, internal capsule, and substantia nigra. Alpha lipoic acid significantly reduced this damage and there were very little neuronal atrophy. Areas of angiogenesis were also seen in the alpha lipoic acid-treated group. In conclusion, the study proves that alpha lipoic acid treatment significantly reduces haloperidol-induced neuronal damage. 相似文献
197.
198.
Mapping human chromosomes by walking with sequence-tagged sites from end fragments of yeast artificial chromosome inserts. 总被引:17,自引:0,他引:17
Sequence-tagged sites (STSs) derived from end fragments of chromosome-specific yeast artificial chromosomes (YACs) can facilitate the assembly of an overlapping YAC/STS map. Contigs form rapidly by iteratively screening YAC collections with end-fragment STSs from YACs that have not yet been detected by any previous STS. The map is rendered rapidly useful during its assembly by incorporating supplementary STSs from genes and genetic linkage probes with known locations. Methods for the systematic development and testing of the end-fragments STSs are given here, and a group of 100 STSs is presented for the X chromosome. The mapping strategy is shown to be successful in simulations with portions of the X chromosome already largely mapped into overlapping YACs by other means. 相似文献
199.
The mycotoxin citrinin, is produced by several species of Penicillium, Aspergillus and Monascus, and is capable of inducing cytotoxicity, oxidative stress and apoptosis. The aim of the present study was to investigate the effect of citrinin in mouse skeletal muscle cells (C2C12) and to overcome the cellular adverse effects by supplementing green tea extract (GTE) rich in polyphenols. C2C12 myoblasts were differentiated to myotubes and were exposed to citrinin in a dose dependent manner (0–100 µM) for 24 h and IC50 value was found to be 100 µM that resulted in decreased cell viability, increased LDH leakage and compromised membrane integrity. Mitochondrial membrane potential loss, increased accumulation of intracellular ROS and sub G1 phase of cell cycle was observed. To ameliorate the cytotoxic effects of CTN, C2C12 cells were pretreated with GTE (20, 40, 80 µg/ml) for 2 h followed by citrinin (100 µM) treatment for 24 h. GTE pretreatment combated citrinin-induced cytotoxicity and oxidative stress. GTE at 40 and 80 µg/ml significantly promoted cell survival and upregulated antioxidant enzyme activities (CAT, SOD, GPx) and endogenous antioxidant GSH, while the gene and protein expression levels were significantly restored through its effective antioxidant mechanism. Present study results suggested the antioxidant properties of GTE as a herbal source in ameliorating the citrinin-induced oxidative stress. 相似文献
200.
Jerzy Woyke Jerzy Wilde Maria Wilde Venkataramegowda Sivaram Cleofas Cervancia Narajanappa Nagaraja Muniswamyreddy Reddy 《Journal of Insect Behavior》2008,21(6):481-494
Defense behavior of three, free living giant (Megapis) honey bee subspecies, Apis laboriosa, A. dorsata dorsata and A. dorsata breviligula, was compared. Disturbed worker bees responded with characteristic dorso-ventral defense body twisting (DBT). Workers of
A. laboriosa twisted the thorax by 55°, and the two other A. dorsata subspecies by about 10° more. A. laboriosa workers raised the tip of the abdomen by 90° and workers of the two other bee subspecies by about 20° higher. Differences
in those traits were highly significant between A. laboriosa and both A. dorsata subspecies, but were not significant between those two subspecies. The whole cycle of DBT was the most vigorous in A. d. breviligula (0.11 s), and it was twice as vigorous as in A. d. dorsata (0.26 s) and trice as in A. laboriosa (0.32 s). A. laboriosa twisted the body together with wings folded over the abdomen, while the two A. dorsata subspecies raised the abdomen between spread wings. This supports the opinion to treat A. laboriosa as a separate species.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献