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321.
The Notch pathway in podocytes plays a role in the development of glomerular disease 总被引:1,自引:0,他引:1
Niranjan T Bielesz B Gruenwald A Ponda MP Kopp JB Thomas DB Susztak K 《Nature medicine》2008,14(3):290-298
322.
Vasileios I. Athanasopoulos Keshavan Niranjan Robert A. Rastall 《Journal of Molecular Catalysis .B, Enzymatic》2004,27(4-6):215-219
A novel 1,6-α-
-mannosidase was produced by Aspergillus phoenicis grown on a commercial manno-oligosaccharide preparation in liquid culture. The enzyme hydrolysed only α-
-Manp-(1→6)-
-Manp and did not act on α-
-Manp-(1→2)-
-Manp, or α-
-Manp-(1→3)-
-Manp. The 1,6-α-
-mannosidase was used for synthesis of manno-oligosaccharides by reverse hydrolysis reaction. The highest yields, expressed as percentages (w/w) of total sugar, were 21% mannobiose and 5% mannotriose, and they were obtained with 45% (w/w) initial mannose concentration at pH 4.5 after 12 days incubation at 55 °C. The disaccharide and trisaccharide products were separated and their structures determined by methylation analysis. Only 1–6 linkages were found in both of them. 相似文献
323.
Fnu Nagajyothi Mahalia S. Desruisseaux Niranjan Thiruvur Louis M. Weiss Vicki L. Braunstein Chris Albanese Mauro M. Teixeira Cecilia J. De Almeida Michael P. Lisanti Philipp E. Scherer Herbert B. Tanowitz 《Obesity (Silver Spring, Md.)》2008,16(9):1992-1997
Infection with Trypanosoma cruzi, the etiologic agent of Chagas disease is accompanied by an intense inflammatory reaction. Our laboratory group has identified adipose tissue as one of the major sites of inflammation during disease progression. Because adipose tissue is composed of many cell types, we were interested in investigating whether the adipocyte per se was a source of inflammatory mediators in this infection. Cultured adipocytes were infected with the Tulahuen strain of T. cruzi for 48–96 h. Immunoblot and quantitative PCR (qPCR) analyses demonstrated an increase in the expression of proinflammatory cytokines and chemokines, including interleukin (IL)‐1β, interferon‐γ, tumor necrosis factor‐α, CCL2, CCL5, and CXCL10 as well as an increase in the expression of Toll‐like receptors‐2 and 9 and activation of the notch pathway. Interestingly, caveolin‐1 expression was reduced while cyclin D1 and extracellular signal‐regulated kinase (ERK) expression was increased. The expression of PI3kinase and the activation of AKT (phosphorylated AKT) were increased suggesting that infection may induce components of the insulin/IGF‐1 receptor cascade. There was an infection‐associated decrease in adiponectin and peroxisome proliferator‐activated receptor‐γ (PPAR‐γ). These data provide a mechanism for the increase in the inflammatory phenotype that occurs in T. cruzi‐infected adipocytes. Overall, these data implicate the adipocyte as an important target of T. cruzi, and one which contributes significantly to the inflammatory response observed in Chagas disease. 相似文献
324.
Cross-clade protective immune responses to influenza viruses with H5N1 HA and NA elicited by an influenza virus-like particle 总被引:2,自引:0,他引:2
Bright RA Carter DM Crevar CJ Toapanta FR Steckbeck JD Cole KS Kumar NM Pushko P Smith G Tumpey TM Ross TM 《PloS one》2008,3(1):e1501
Background
Vaccination is a cost-effective counter-measure to the threat of seasonal or pandemic outbreaks of influenza. To address the need for improved influenza vaccines and alternatives to egg-based manufacturing, we have engineered an influenza virus-like particle (VLP) as a new generation of non-egg or non-mammalian cell culture-based candidate vaccine.Methodology/Principal Findings
We generated from a baculovirus expression system using insect cells, a non-infectious recombinant VLP vaccine from both influenza A H5N1 clade 1 and clade 2 isolates with pandemic potential. VLPs were administered to mice in either a one-dose or two-dose regimen and the immune responses were compared to those induced by recombinant hemagglutinin (rHA). Both humoral and cellular responses were analyzed. Mice vaccinated with VLPs were protected against challenge with lethal reassortant viruses expressing the H5N1 HA and NA, regardless if the H5N1 clade was homologous or heterologous to the vaccine. However, rHA-vaccinated mice showed considerable weight loss and death following challenge with the heterovariant clade virus. Protection against death induced by VLPs was independent of the pre-challenge HAI titer or cell-mediated responses to HA or M1 since vaccinated mice, with low to undetectable cross-clade HAI antibodies or cellular responses to influenza antigens, were still protected from a lethal viral challenge. However, an apparent association rate of antibody binding to HA correlated with protection and was enhanced using VLPs, particularly when delivered intranasally, compared to rHA vaccines.Conclusion/Significance
This is the first report describing the use of an H5N1 VLP vaccine created from a clade 2 isolate. The results show that a non-replicating virus-like particle is effective at eliciting a broadened, cross-clade protective immune response to proteins from emerging H5N1 influenza isolates giving rise to a potential pandemic influenza vaccine candidate for humans that can be stockpiled for use in the event of an outbreak of H5N1 influenza. 相似文献325.
326.
Hughes TV Xu G Wetter SK Connolly PJ Emanuel SL Karnachi P Pollack SR Pandey N Adams M Moreno-Mazza S Middleton SA Greenberger LM 《Bioorganic & medicinal chemistry letters》2008,18(17):4896-4899
A novel 5-[1,3,4-oxadiazol-2-yl]-N-aryl-4,6-pyrimidine diamine was synthesized and found to have potent dual EGFR/HER2 kinase inhibitory activity. The structure-based drug design of this molecule as well as the kinase and cellular inhibition of HER2 kinase dependent cell lines will be discussed. 相似文献
327.
Xu G Abad MC Connolly PJ Neeper MP Struble GT Springer BA Emanuel SL Pandey N Gruninger RH Adams M Moreno-Mazza S Fuentes-Pesquera AR Middleton SA 《Bioorganic & medicinal chemistry letters》2008,18(16):4615-4619
Members of a novel class of 4-amino-6-arylamino-pyrimidine-5-carbaldehyde hydrazones were identified as potent dual ErbB-2/EGFR kinase inhibitors using concept-guided design approach. These compounds inhibited the growth of ErbB-2 over-expressing human tumor cell lines (BT474, N87, and SK-BR-3) in vitro. Compound 15 emerged as a key lead and showed significant ability to inhibit growth factor-induced receptor phosphorylation in SK-BR-3 cells (IC(50)=54 nM) and cellular proliferation in vitro (IC(50)=14, 58, and 58 nM for BT474, N87, and SK-BR-3 respectively). The X-ray co-crystal structure of EGFR with a close analog (17) was determined and validated our design rationale. 相似文献
328.
329.
330.
Investigation of jumbo squid (Dosidicus gigas) skin gelatin peptides for their in vitro antioxidant effects 总被引:19,自引:0,他引:19
Peptides derived from tryptic hydrolysate of jumbo squid (Dosidicus gigas) skin gelatin were assessed for their antioxidant properties in different in vitro assay systems. The hydrolysate itself exhibited a strong lipid peroxidation inhibition and it was much higher than that of natural antioxidant, alpha-tocopherol. In addition, it could scavenge highly active free radicals in oxidative systems, in the order of hydroxyl and carbon-centered radicals. Two representative peptides with comparatively higher antioxidant potency were purified and characterized as Phe-Asp-Ser-Gly-Pro-Ala-Gly-Val-Leu (880.18 Da) and Asn-Gly-Pro-Leu-Gln-Ala-Gly-Gln-Pro-Gly-Glu-Arg (1241.59 Da). Furthermore, viability of radical-mediated oxidation-induced human lung fibroblasts was enhanced following the treatment of two peptides. However it did not exhibit substantial ion chelation, and we presumed that the observed radical scavenging potency of these peptides play a vital role for their strong antioxidant activity. Based on our results we suggest that hydrophobic amino acids present in peptide sequences contributed greatly for observed antioxidant activities. 相似文献