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排序方式: 共有167条查询结果,搜索用时 31 毫秒
91.
92.
Noronha G Barrett K Cao J Dneprovskaia E Fine R Gong X Gritzen C Hood J Kang X Klebansky B Li G Liao W Lohse D Mak CC McPherson A Palanki MS Pathak VP Renick J Soll R Splittgerber U Wrasidlo W Zeng B Zhao N Zhou Y 《Bioorganic & medicinal chemistry letters》2006,16(21):5546-5550
We report the discovery and preliminary SAR studies of a series of structurally novel benzotriazine core based small molecules as inhibitors of Src kinase. To the best of our knowledge, benzotriazine template based compounds have not been reported as kinase inhibitors. The 3-(2-(1-pyrrolidinyl)ethoxy)phenyl analogue (43) was identified as one of the most potent inhibitors of Src kinase. 相似文献
93.
94.
George?M?WarimweEmail author Gema?Lorenzo Elena?Lopez-Gil Arturo?Reyes-Sandoval Matthew?G?Cottingham Alexandra?J?Spencer Katharine?A?Collins Matthew?DJ?Dicks Anita?Milicic Amar?Lall Julie?Furze Alison?V?Turner Adrian?VS?Hill Alejandro?Brun Sarah?C?Gilbert 《Virology journal》2013,10(1):349
Background
Rift Valley Fever (RVF) is a viral zoonosis that historically affects livestock production and human health in sub-Saharan Africa, though epizootics have also occurred in the Arabian Peninsula. Whilst an effective live-attenuated vaccine is available for livestock, there is currently no licensed human RVF vaccine. Replication-deficient chimpanzee adenovirus (ChAd) vectors are an ideal platform for development of a human RVF vaccine, given the low prevalence of neutralizing antibodies against them in the human population, and their excellent safety and immunogenicity profile in human clinical trials of vaccines against a wide range of pathogens.Methods
Here, in BALB/c mice, we evaluated the immunogenicity and efficacy of a replication-deficient chimpanzee adenovirus vector, ChAdOx1, encoding the RVF virus envelope glycoproteins, Gn and Gc, which are targets of virus neutralizing antibodies. The ChAdOx1-GnGc vaccine was assessed in comparison to a replication-deficient human adenovirus type 5 vector encoding Gn and Gc (HAdV5-GnGc), a strategy previously shown to confer protective immunity against RVF in mice.Results
A single immunization with either of the vaccines conferred protection against RVF virus challenge eight weeks post-immunization. Both vaccines elicited RVF virus neutralizing antibody and a robust CD8+ T cell response.Conclusions
Together the results support further development of RVF vaccines based on replication-deficient adenovirus vectors, with ChAdOx1-GnGc being a potential candidate for use in future human clinical trials.95.
Moorthy S.S. Palanki Abhijit Bhat Ben Bolanos Florence Brunel Joselyn Del Rosario Danielle Dettling Mark Horn Rodney Lappe Ryan Preston Annette Sievers Nebojsa Stankovic Gary Woodnut Gang Chen 《Bioorganic & medicinal chemistry letters》2013,23(2):402-406
Human growth hormone was conjugated to a carrier aldolase antibody, using a novel linker by connecting a disulphide bond in growth hormone to a lysine-94 amine located on the Fab arm of the antibody. The resulting CovX body showed reduced affinity towards human growth hormone receptor, reduced cell-based activity, but improved pharmacodynamic properties. We have demonstrated that this CovX-body, given once a week, showed comparable activity as growth hormone given daily in an in vivo hypophysectomized rat model. 相似文献
96.
Jiang W Couroucli XI Wang L Barrios R Moorthy B 《Biochemical and biophysical research communications》2011,(1):79-85
Background/aims
TEC, a member of the TEC family of non-receptor type protein tyrosine kinases, has recently been suggested to play a role in hepatocyte proliferation and liver regeneration. This study aims to investigate the putative mechanisms of TEC kinase regulation of hepatocyte differentiation, i.e. to explore which signaling pathway TEC is involved in, and how TEC is activated in hepatocyte after hepatectomy and hepatocyte growth factor (HGF) stimulation.Methods
We performed immunoprecipitation (IP) and immunoblotting (IB) to examine TEC tyrosine phosphorylation after partial hepatectomy in mice and HGF stimulation in WB F-344 hepatic cells. The TEC kinase activity was determined by in vitro kinase assay. Reporter gene assay, antisense oligonucleotide and TEC dominant negative mutant (TECKM) were used to examine the possible signaling pathways in which TEC is involved. The cell proliferation rate was evaluated by 3H-TdR incorporation.Results
TEC phosphorylation and kinase activity were increased in 1 h after hepatectomy or HGF treatment. TEC enhanced the activity of Elk and serum response element (SRE). Inhibition of MEK1 suppressed TEC phosphorylation. Blocking TEC activity dramatically decreased the activation of Erk. Reduced TEC kinase activity also suppressed the proliferation of WB F-344 cells. These results suggest TEC is involved in the Ras-MAPK pathway and acts between MEK1 and Erk.Conclusions
TEC promotes hepatocyte proliferation and regeneration and is involved in HGF-induced Erk signaling pathway. 相似文献97.
Mukhopadhyay P Chakraborty S Ponnusamy MP Lakshmanan I Jain M Batra SK 《Biochimica et biophysica acta》2011,1815(2):224-240
Mucins are high molecular weight, multifunctional glycoproteins comprised of two structural classes-the large transmembrane mucins and the gel-forming or secreted mucins. The primary function of mucins is to protect and lubricate the luminal surfaces of epithelium-lined ducts in the human body. Recent studies have identified a differential expression of both membrane bound (MUC1, MUC4 and MUC16) and secreted mucins (MUC2, MUC5AC, MUC5B and MUC6) in breast cancer tissues when compared with the non-neoplastic breast tissues. Functional studies have also uncovered many unique roles of mucins during the progression of breast cancer, which include modulation in proliferative, invasive and metastatic potential of tumor cells. Mucins function through many unique domains that can form complex association with various signaling molecules including growth factor receptors and intercellular adhesion molecules. While there is growing information about mucins in various malignancies including breast cancer, no focused review is there on the expression and functional roles of mucins in breast cancer. In this present review, we have discussed the differential expression and functional roles of mucins in breast cancer. The potential of mucins as diagnostic and prognostic markers and as therapeutic targets in breast cancer have also been discussed. 相似文献
98.
Jarugu Narasimha Moorthy Parthasarathy Venkatakrishnan Govardhan Savitha Richard G Weiss 《Photochemical & photobiological sciences》2006,5(10):903-913
We have examined the photobehavior of a set of isomers of 2-pyranone-annulated stilbenes (6-styrylcoumarin , 7-styrylcoumarin , 4-methyl-6-styrylcoumarin , and 4-methyl-7-styrylcoumarin, ) in their crystalline phases. While the cis isomers of undergo cis-->trans photoisomerizations in the solid state, cis- and the trans isomers of do not; the trans isomer of undergoes photo-induced intermolecular reactions. Solution-state irradiations of the trans isomers of lead to the cis isomers quite readily, as does cis- lead to trans-, which suggests that the absence of geometric isomerization of the trans isomers and the lack of reactivity of cis- in the solid state are due to molecular packing effects. X-Ray crystal structural analyses of reveal interesting conformational preferences for the styrenic moieties and differences in the total 'free' volumes within the lattices, but neither factor explains satisfactorily why some of the molecules undergo geometric isomerizations in their single crystals and others do not. Using the PLATON program, we have located the sizes and positions of 'void volumes' within the crystal lattices, and identified trajectories necessary for atomic motions to lead to geometric isomerizations to understand the reactivities of . The voids in the reactive cis isomers of crystals are located along the trajectories needed for geometric isomerization. The relevant voids in the crystals of cis- and the trans isomers of and (the non-isomerizing molecules for which suitable crystals could be grown for X-ray analyses) are located along a trajectory that does not permit isomerization. We hypothesize that the classical momentum gained from the initial motions that are facilitated due to the voids in the crystals of the cis isomers of , as well as the heat dissipated to the local environment by internal conversions and vibronic cascade of the Franck-Condon states, helps to drive the system over potential energy barriers that would not be possible otherwise. Cis- and the trans isomers of and , as well as other examples from the literature in which geometric isomerizations do or do not occur in the solid state, also follow the predictions based upon the PLATON analyses. On these bases, it is suggested that the methodology described may be generally applicable for predicting when geometric isomerizations (and possibly other reactive processes) in crystalline materials will occur. 相似文献
99.
Paradoxical DNA repair and peroxide resistance gene conservation in Bacillus pumilus SAFR-032 总被引:1,自引:0,他引:1
Gioia J Yerrapragada S Qin X Jiang H Igboeli OC Muzny D Dugan-Rocha S Ding Y Hawes A Liu W Perez L Kovar C Dinh H Lee S Nazareth L Blyth P Holder M Buhay C Tirumalai MR Liu Y Dasgupta I Bokhetache L Fujita M Karouia F Eswara Moorthy P Siefert J Uzman A Buzumbo P Verma A Zwiya H McWilliams BD Olowu A Clinkenbeard KD Newcombe D Golebiewski L Petrosino JF Nicholson WL Fox GE Venkateswaran K Highlander SK Weinstock GM 《PloS one》2007,2(9):e928
100.
Uropathogenic E. coli (UPEC) infection in vivo is characterized by invasion of bladder umbrella epithelial cells followed by endosomal escape and proliferation in the cytoplasm to form intracellular bacterial communities. By contrast, UPEC infection in tissue culture models results in bacteria being trapped within Lamp1‐positive endosomes where proliferation is limited. Pharmacological disruption of the actin cytoskeleton has been shown to facilitate UPEC endosomal escape in vitro and extracellular matrix stiffness is a well‐characterized physiological regulator of actin dynamics; therefore, we hypothesized that substrate stiffness may play a role in UPEC endosomal escape. Using functionalized polyacrylamide substrates, we found that at physiological stiffness, UPEC escaped the endosome and proliferated rapidly in the cytoplasm of bladder epithelial cells. Dissection of the cytoskeletal signaling pathway demonstrated that inhibition of the Rho GTPase RhoB or its effector PRK1 was sufficient to increase cytoplasmic bacterial growth and that RhoB protein level was significantly reduced at physiological stiffness. Our data suggest that tissue stiffness is a critical regulator of intracellular bacterial growth. Due to the ease of doing genetic and pharmacological manipulations in cell culture, this model system may provide a useful tool for performing mechanistic studies on the intracellular life cycle of uropathogens. 相似文献