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121.
The search for safer non-steroidal anti-inflammatory drugs (NSAIDs) continues with the failure of anticipated 'ideal' anti-inflammatory agents, the coxibs, on long-term usage. Increased gastric motility and acidity due to the free carboxy group are involved in the etiology of gastric toxicity, common to conventional NSAIDs. Keeping this fact in mind, it was planned to modify some of the conventional NSAIDs to amino-alcohol ester derivatives, which satisfied the structural requirements for these compounds to possess anticholinergic activity in the intact form. Besides blocking the acidic carboxylic group, incorporation of anticholinergic acivity in these molecules was expected to reduce the gastric toxicity by decreasing gastric acid secretion and motility. Synthesis and pharmacological evaluation of six different N,N-disubstituted amino-ethyl ester derivatives, structurally resembling the amino-alcohol ester class of anticholinergic agents, each for [1,1'-biphenyl]-4-acetic acid (3) and flurbiprofen (10), have been reported as potential substitutes for these NSAIDs, with improved therapeutic profile. All the ester derivatives were found to have sufficient chemical stability in buffers (pH 2.0 and 7.4), ensuring them to be absorbed as intact moieties from the gastrointestinal tract. A significant reduction in ulcerogenic potency in comparison to the parent drugs with a slightly higher anti-inflammatory potency suggests that the majority of these candidates have an improved therapeutic profile over their parent drugs. Hence, a promising novel approach, different from the conventional prodrug concept, has been successfully worked out to overcome the local gastric toxicity, yielding therapeutically better compounds for long-term oral anti-inflammatory therapy. 相似文献
122.
Impedance characteristics of lens tissue has been studied using the AC impedance system (EG&G PARC, model 318) at different low voltage excitations using a Cole-Cole Plot. The extracellular resistance (Re), intracellular resistance (Ri), depressed angle (theta), total impedance (/Z/), and phase angle (phi) of the tissue were measured. The impedance locus between the real part (Z') and imaginary part (Z') of the complex impedance of lens was examined at discrete frequencies ranging from 10 mHz to 10 Hz. A decrease in extra-cellular resistance (Re) and increase in distribution of the factor (alpha) of 56.8 KOmega, 48.1 KOmega, 32.8 KOmega, 13.4 KOmega, and 0.40, 0.43, 0.46, 0.53 were found at 0 mV, 50 mV, 100 mV, and 200 mV, respectively. The total impedance (/Z/) and phase angle (phi) were also evaluated and the observed frequency dependent for the frequency range was tested as a function of excitation voltage. An attempt has been made to explain the effect of voltage stress on lens impedance. 相似文献
123.
124.
Broad-spectrum Blast Resistance Gene Pi-k
h Cloned from Rice Line Tetep Designated as Pi54 总被引:1,自引:0,他引:1
T. R. Sharma A. K. Rai S. K. Gupta N. K. Singh 《Journal of plant biochemistry and biotechnology.》2010,19(1):87-89
Blast disease caused by Magnaporthe oryzae is one of the important biotic stresses of rice. So far more than 85 blast resistance genes have been identified of these more than 14 have already been cloned. A broad spectrum rice blast resistance gene Pi-k h was cloned from the rice line Tetep. The gene was named Pi-k h based on the earlier reports on its genetic analysis in various rice lines. However, with the advances in molecular genetics and genomics of rice, the Pik locus has now been mapped more precisely. Since there are two reports on the mapping of Pi-k h gene from different rice lines, there is some confusion in the naming of this gene. In this report the name of Pi-k h gene cloned from the rice line Tetep has been designated as per the standard guidelines of Committee on Gene Symbolization, Nomenclature and Linkage (CGSNL) and its physical location on rice chromosome 11, which is ~2.5 Mbp away from the Pik locus mapped recently. Hence Pi-k h gene cloned from Tetep is now designated as Pi54. 相似文献
125.
Leonardo Faoro Patrick A. Singleton Gustavo M. Cervantes Frances E. Lennon Nicholas W. Choong Rajani Kanteti Benjamin D. Ferguson Aliya N. Husain Maria S. Tretiakova Nithya Ramnath Everett E. Vokes Ravi Salgia 《The Journal of biological chemistry》2010,285(24):18575-18585
Non-small cell lung cancer (NSCLC) has a poor prognosis and improved therapies are needed. Expression of EphA2 is increased in NSCLC metastases. In this study, we investigated EphA2 mutations in NSCLC and examined molecular pathways involved in NSCLC. Tumor and cell line DNA was sequenced. One EphA2 mutation was modeled by expression in BEAS2B cells, and functional and biochemical studies were conducted. A G391R mutation was detected in H2170 and 2/28 squamous cell carcinoma patient samples. EphA2 G391R caused constitutive activation of EphA2 with increased phosphorylation of Src, cortactin, and p130Cas. Wild-type (WT) and G391R cells had 20 and 40% increased invasiveness; this was attenuated with knockdown of Src, cortactin, or p130Cas. WT and G391R cells demonstrated a 70% increase in focal adhesion area. Mammalian target of rapamycin (mTOR) phosphorylation was increased in G391R cells with increased survival (55%) compared with WT (30%) and had increased sensitivity to rapamycin. A recurrent EphA2 mutation is present in lung squamous cell carcinoma and increases tumor invasion and survival through activation of focal adhesions and actin cytoskeletal regulatory proteins as well as mTOR. Further study of EphA2 as a therapeutic target is warranted. 相似文献
126.
127.
P.A. Wadegaonkar K.A. Bhagwat M.K. Rai 《Plant Cell, Tissue and Organ Culture》2006,84(2):100202-100204
Direct rooting from leaf explants of Withania somnifera was achieved on half strength Murashige and Skoog’s medium supplemented with 15 g l−1 sucrose, and different concentrations of growth regulators. Basal medium supplemented with 2.85 μM indoleacetic acid and
9.85 μM indolebutyric acid achieved maximum number of roots with 100% response. The roots were cultured on MS liquid medium
for the establishment of root-organ culture with the same plant growth regulators and incubated on an orbital shaker at 80 rpm
at 25 ± 2 °C. A root biomass of 6.15 ± 0.17 g was obtained after 5 weeks. When 1 g roots were inoculated to 2.5 l bubble column
reactor, 47 g roots were obtained after 6 weeks. The concentration of alkaloids was increased as compared to field grown roots.
The maximum concentration of withanolides (10 mg g−1 dry weight) was obtained in the bioreactor. 相似文献
128.
Zebra fish Dnmt1 and Suv39h1 regulate organ-specific terminal differentiation during development 总被引:1,自引:0,他引:1
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Rai K Nadauld LD Chidester S Manos EJ James SR Karpf AR Cairns BR Jones DA 《Molecular and cellular biology》2006,26(19):7077-7085
DNA methylation and histone methylation are two key epigenetic modifications that help govern heterochromatin dynamics. The roles for these chromatin-modifying activities in directing tissue-specific development remain largely unknown. To address this issue, we examined the roles of DNA methyltransferase 1 (Dnmt1) and the H3K9 histone methyltransferase Suv39h1 in zebra fish development. Knockdown of Dnmt1 in zebra fish embryos caused defects in terminal differentiation of the intestine, exocrine pancreas, and retina. Interestingly, not all tissues required Dnmt1, as differentiation of the liver and endocrine pancreas appeared normal. Proper differentiation depended on Dnmt1 catalytic activity, as Dnmt1 morphants could be rescued by active zebra fish or human DNMT1 but not by catalytically inactive derivatives. Dnmt1 morphants exhibited dramatic reductions of both genomic cytosine methylation and genome-wide H3K9 trimethyl levels, leading us to investigate the overlap of in vivo functions of Dnmt1 and Suv39h1. Embryos lacking Suv39h1 had organ-specific terminal differentiation defects that produced largely phenocopies of Dnmt1 morphants but retained wild-type levels of DNA methylation. Remarkably, suv39h1 overexpression rescued markers of terminal differentiation in Dnmt1 morphants. Our results suggest that Dnmt1 activity helps direct histone methylation by Suv39h1 and that, together, Dnmt1 and Suv39h1 help guide the terminal differentiation of particular tissues. 相似文献
129.
In the present study, we have investigated the effects of NaCl concentrations on the growth and phosphate metabolism of an
Anabaena doliolum strain isolated from a paddy field, in order to determine the possible effects of salinization. Growth rate, chlorophyll
content, and protein content decreased with increasing salt concentration in the growth medium, while carbohydrate concentration
increased. Phosphate content and phosphate uptake rate decreased. There was an increase in total alkaline phosphatase activity,
with an approximately 7-fold increase in extracellular activity compensating for an approximately 3-fold decrease in cell-bound
activity. NaCl effects on protein and chlorophyll concentrations were greater in P-deficient medium, while presence or absence
of P in the medium had little effect on cellular carbohydrate concentrations. It is concluded that growth in high salt likely
leads to reduced phosphate uptake in A. doliolum. 相似文献
130.
MukB is a bacterial SMC (structural maintenance of chromosome) protein required for faithful chromosome segregation in Escherichia coli. We report here that purified MukB introduces right-handed knots into DNA in the presence of type-2 topoisomerase, indicating that the protein promotes intramolecular DNA condensation. The pattern of generated knots suggests that MukB, similar to eukaryotic condensins, stabilizes large right-handed DNA loops. In contrast to eukaryotic condensins, however, the net supercoiling stabilized by MukB was negative. Furthermore, DNA reshaping by MukB did not require ATP. These data establish that bacterial condensins alter the shape of double-stranded DNA in vitro and lend support to the notions that the right-handed knotting is the most conserved biochemical property of condensins. Finally, we found that MukB can be eluted from a heparin column in two distinct forms, one of which is inert in DNA binding or reshaping. Furthermore, we find that the activity of MukB is reversibly attenuated during chromatographic separation. Thus, MukB has a unique set of topological properties, compared with other SMC proteins, and is likely to exist in two different conformations. 相似文献