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61.
The red quinone C20H14O8 (mp 322–324), named bikaverin was isolated from mycelium ofGibberella fujikuroi. Bikaverin is specifically effective againstLeishmania brasiliensis while is not effective against other protozoa, bacteria and fungi. For production of bikaverin in a submerged culture the
most convenient media are those with a natural source of nitrogen (corn-steep liquor, soyabean meal) in which the content
of bikaverin ranged from 1.0 to 1.7% of dry weight of mycelium. 相似文献
62.
Raf kinases: function, regulation and role in human cancer 总被引:3,自引:0,他引:3
Leicht DT Balan V Kaplun A Singh-Gupta V Kaplun L Dobson M Tzivion G 《Biochimica et biophysica acta》2007,1773(8):1196-1212
The Ras-Raf-MAPK pathway regulates diverse physiological processes by transmitting signals from membrane based receptors to various nuclear, cytoplasmic and membrane-bound targets, coordinating a large variety of cellular responses. Function of Raf family kinases has been shown to play a role during organism development, cell cycle regulation, cell proliferation and differentiation, cell survival and apoptosis and many other cellular and physiological processes. Aberrations along the Ras-Raf-MAPK pathway play an integral role in various biological processes concerning human health and disease. Overexpression or activation of the pathway components is a common indicator in proliferative diseases such as cancer and contributes to tumor initiation, progression and metastasis. In this review, we focus on the physiological roles of Raf kinases in normal and disease conditions, specifically cancer, and the current thoughts on Raf regulation. 相似文献
63.
Paul S. Humphries John W. Benbow Paul D. Bonin David Boyer Shawn D. Doran Richard K. Frisbie David W. Piotrowski Gayatri Balan Bruce M. Bechle Edward L. Conn Kenneth J. Dirico Robert M. Oliver Walter C. Soeller James A. Southers Xiaojing Yang 《Bioorganic & medicinal chemistry letters》2009,19(9):2400-2403
The development of a series of novel 1,2,3,4-tetrahydroisoquinolin-1-ones as antagonists of G protein-coupled receptor 40 (GPR40) is described. The synthesis, in vitro inhibitory values for GPR40, in vitro microsomal clearance and rat in vivo clearance data are discussed. Initial hits displayed high rat in vivo clearances that were higher than liver blood flow. Optimization of rat in vivo clearance was achieved and led to the identification of 15i, whose rat oral pharmacokinetic data is reported. 相似文献
64.
Gayatri Balan Jonathan Bauman Samit Bhattacharya Mayda Castrodad David R. Healy Michael Herr Paul Humphries Sandra Jennings Amit S. Kalgutkar Brendon Kapinos Vishal Khot Kimberly Lazarra Mei Li Yan Li Constantin Neagu Robert Oliver David W. Piotrowski David Price Hong Qi Holly A. Simmons Vishwas M. Paralkar 《Bioorganic & medicinal chemistry letters》2009,19(12):3328-3332
The design and profile of a series of zwitterionic calcium sensing receptor negative allosteric modulators is described. Evaluation of key analogues using a rat model demonstrate a robust response, significantly improved potency over ronacaleret and have the potential as an oral, anabolic treatment for osteoporosis. 相似文献
65.
Green kiwifruit modulates the colonic microbiota in growing pigs 总被引:1,自引:0,他引:1
Aims: To investigate whether green kiwifruit modulates the composition of colonic microbiota in growing pigs. Methods and Results: Thirty‐two pigs were fed the control diet or one of the three test diets containing either cellulose, freeze‐dried kiwifruit or kiwifruit fibre as the sole fibre source for 14‐day study. A Ward’s dendrogram of similarity cluster analysis on PCR‐DGGE gels revealed that inclusion of freeze‐dried kiwifruit and kiwifruit fibre into diets altered the bacterial community, indicating the presence of two distinct clusters. Quantification of different bacterial groups by qPCR demonstrated that pigs fed the freeze‐dried kiwifruit or kiwifruit fibre diets had a significantly higher number (P < 0·05) of total bacteria and Bacteroides group and a lower number of Enterobacteria and Escherichia coli group, as well as a greater ratio of Lactobacillus to Enterobacteria when compared to pigs fed the control or cellulose diets. Conclusions: Green kiwifruit, mainly because of fibre, modulated the colonic microbiota, leading to an improved intestinal environment in growing pigs. Significance and Impact of the Study: This is the first report regarding the effect of green kiwifruit on gut microbiota using the in vivo pig model. These results provide the first evidence of interaction between green kiwifruit and colonic microbiota. 相似文献
66.
Amy?P. Guilfoyle Chandrika?N. Deshpande Gerhard Schenk Megan?J. Maher Mika Jormakka 《Bioscience reports》2014,34(6)
GDP release from GTPases is usually extremely slow and is in general assisted by external factors, such as association with guanine exchange factors or membrane-embedded GPCRs (G protein-coupled receptors), which accelerate the release of GDP by several orders of magnitude. Intrinsic factors can also play a significant role; a single amino acid substitution in one of the guanine nucleotide recognition motifs, G5, results in a drastically altered GDP release rate, indicating that the sequence composition of this motif plays an important role in spontaneous GDP release. In the present study, we used the GTPase domain from EcNFeoB (Escherichia coli FeoB) as a model and applied biochemical and structural approaches to evaluate the role of all the individual residues in the G5 loop. Our study confirms that several of the residues in the G5 motif have an important role in the intrinsic affinity and release of GDP. In particular, a T151A mutant (third residue of the G5 loop) leads to a reduced nucleotide affinity and provokes a drastically accelerated dissociation of GDP. 相似文献
67.
Irnayuli R. Sitepu Mingjie Jin J. Enrique Fernandez Leonardo da Costa Sousa Venkatesh Balan Kyria L. Boundy-Mills 《Applied microbiology and biotechnology》2014,98(17):7645-7657
Microbial oil is a potential alternative to food/plant-derived biodiesel fuel. Our previous screening studies identified a wide range of oleaginous yeast species, using a defined laboratory medium known to stimulate lipid accumulation. In this study, the ability of these yeasts to grow and accumulate lipids was further investigated in synthetic hydrolysate (SynH) and authentic ammonia fiber expansion (AFEX?)-pretreated corn stover hydrolysate (ACSH). Most yeast strains tested were able to accumulate lipids in SynH, but only a few were able to grow and accumulate lipids in ACSH medium. Cryptococcus humicola UCDFST 10-1004 was able to accumulate as high as 15.5 g/L lipids, out of a total of 36 g/L cellular biomass when grown in ACSH, with a cellular lipid content of 40 % of cell dry weight. This lipid production is among the highest reported values for oleaginous yeasts grown in authentic hydrolysate. Preculturing in SynH media with xylose as sole carbon source enabled yeasts to assimilate both glucose and xylose more efficiently in the subsequent hydrolysate medium. This study demonstrates that ACSH is a suitable medium for certain oleaginous yeasts to convert lignocellullosic sugars to triacylglycerols for production of biodiesel and other valuable oleochemicals. 相似文献
68.
Gangaraju Rajashekhar Ahmed Ramadan Chandrika Abburi Breedge Callaghan Dmitry O. Traktuev Carmella Evans-Molina Raj Maturi Alon Harris Timothy S. Kern Keith L. March 《PloS one》2014,9(1)
Diabetic retinopathy (DR) is the leading cause of blindness in working-age adults. Early stage DR involves inflammation, vascular leakage, apoptosis of vascular cells and neurodegeneration. In this study, we hypothesized that cells derived from the stromal fraction of adipose tissue (ASC) could therapeutically rescue early stage DR features. Streptozotocin (STZ) induced diabetic athymic nude rats received single intravitreal injection of human ASC into one eye and saline into the other eye. Two months post onset of diabetes, administration of ASC significantly improved “b” wave amplitude (as measured by electroretinogram) within 1–3 weeks of injection compared to saline treated diabetic eyes. Subsequently, retinal histopathological evaluation revealed a significant decrease in vascular leakage and apoptotic cells around the retinal vessels in the diabetic eyes that received ASC compared to the eyes that received saline injection. In addition, molecular analyses have shown down-regulation in inflammatory gene expression in diabetic retina that received ASC compared to eyes that received saline. Interestingly, ASC were found to be localized near retinal vessels at higher densities than seen in age matched non-diabetic retina that received ASC. In vitro, ASC displayed sustained proliferation and decreased apoptosis under hyperglycemic stress. In addition, ASC in co-culture with retinal endothelial cells enhance endothelial survival and collaborate to form vascular networks. Taken together, our findings suggest that ASC are able to rescue the neural retina from hyperglycemia-induced degeneration, resulting in importantly improved visual function. Our pre-clinical studies support the translational development of adipose stem cell-based therapy for DR to address both retinal capillary and neurodegeneration. 相似文献
69.
Chandrika J. Piyathilake Gary L. Johanning Andra R. Frost Martin A. Whiteside Upender Marine William E. Grizzle Douglas C. Heimburger Alain Niveleau 《Biotechnic & histochemistry》2000,75(6):251-258
The in vitro radiolabeled methyl incorporation assay, a commonly used technique to evaluate global methylation of DNA, has some disadvantages and limitations. The purpose of the present study was to compare the results of global DNA methylation evaluated by radiolabeled methyl incorporation (CPM/μg of DNA) with immunohistochemical staining of the same tissue sections with a monoclonal antibody developed against 5-methylcytosine (5-mc). We used archival specimens of squamous cell cancer (SCC) of the human lung with a matched uninvolved specimen (n = 18 pairs) and 18 lung specimens from subjects without lung cancer (noncancer specimens) to make this comparison. The immunostaining for 5-mc was reported as a percentage of cells positive for staining as well as a weighted average of the intensity score. The results suggested that both radiolabeled methyl incorporation assay and immunostaining for 5-mc can be used to demonstrate hypomethylation of DNA in SCC tissues compared to matched uninvolved tissues. An advantage of immunostaining, however, is its ability to demonstrate hypomethylation of SCC compared to adjacent bronchial mucosa on the same archival specimen, obviating the need to use sections from both SCC and matched uninvolved tissues. Only by using the immunostaining technique were we able to document a statistically significant difference in DNA methylation between SCC and noncancer tissues. We conclude that the immunostaining technique has advantages over the radiolabeled methyl incorporation assay and may be best suited for evaluation of global DNA methylation when the methylation status of cancer cannot be normalized by methyl incorporation of normal tissues or when the number of samples available for evaluation is small. 相似文献
70.
Design of experiments in the biodegradation of phenol using immobilized Pseudomonas pictorum (NICM-2077) on activated carbon 总被引:1,自引:0,他引:1
G. Annadurai S. Mathalai Balan T. Murugesan 《Bioprocess and biosystems engineering》2000,22(2):101-107
Pseudomonas pictorum (NICM-2077) immobilized on various matrices are used to protect the microbes from confronting shock loads of concentrated phenol. The cells were immobilized in activated carbon and were used in biodegradation of phenol. Biodegradation of phenol using immobilized Activated Carbon matrix played an important role in reducing the toxicity of phenol. The degradation was carried and using the Box-Behnken model and analysis of variance have been applied to the experimental degradation studies. Response surface method with three levels of phenol concentration (0.200, 0.400, 0.600 g/l), activated carbon (0.5, 1.0, 1.5 g/l) and pH (7, 8, 9) were used in the identification of significant effects and interactions in the biodegradation studies. Phenol removal rate increases especially when the degradation medium was supplemented with utilizable carbon sources. A first-order polynomial regression model, which was used at first for analysis of the experiment had a significant lack of fit. Therefore, linear and quadratic terms were incorporated into the regression model through variable selection procedures. Effect of incubation phenol concentration, activated carbon and pH were significant. The predicted values using Box-Behnken model was found to be in close agreement with the experimental values, as indicated by the correlation coefficient values of 0.9463. 相似文献