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排序方式: 共有493条查询结果,搜索用时 15 毫秒
51.
Ramasamy KS Amador RB Habib Q Rong F Han X Li DY Huang J Hong Z An H 《Nucleosides, nucleotides & nucleic acids》2005,24(10-12):1947-1970
The synthesis of pyrazolo[4,3-d]pyrimidine nucleoside library using solid-phase parallel synthesis methodology is described. Glycosylation of the trimethylsilyl (TMS) derivative of 1- and 2-(methyl)-1H and 2H-pyrazolo[4,3-d]pyrimidine-5,7-(4H, 6H)-dione (5) with 1-O-acetyl-2,3,5-tri-O-benzoyl-D-ribofuranose in the presence of TMS triflate provided two novel protected nucleosides 6 and 7. The structures of 6 and 7 were assigned by 1H and 2D NMR experiments. Nucleosides 6 and 7 were then transformed to the key intermediates 12 and 15 respectively. Reaction of 12 and 15 with MMTCl resin in the presence of 2,6-lutidine afforded the necessary scaffolds B and C. Different amines (96) were introduced selectively by nucleophilic substitution on scaffolds B and C using solid-phase parallel semi-automated synthesizer. Cleavage of the products from the solid support with 30% HFIP in a parallel fashion yielded nucleoside libraries simultaneously, and they were analyzed and characterized by high-throughput LC-MS. 相似文献
52.
Brian J. Hawkins Krishna M. Irrinki Karthik Mallilankaraman Yu-Chin Lien Youjun Wang Cunnigaiper D. Bhanumathy Ramasamy Subbiah Michael F. Ritchie Jonathan Soboloff Yoshihiro Baba Tomohiro Kurosaki Suresh K. Joseph Donald L. Gill Muniswamy Madesh 《The Journal of cell biology》2010,190(3):391-405
Oxidant stress influences many cellular processes, including cell growth, differentiation, and cell death. A well-recognized link between these processes and oxidant stress is via alterations in Ca2+ signaling. However, precisely how oxidants influence Ca2+ signaling remains unclear. Oxidant stress led to a phenotypic shift in Ca2+ mobilization from an oscillatory to a sustained elevated pattern via calcium release–activated calcium (CRAC)–mediated capacitive Ca2+ entry, and stromal interaction molecule 1 (STIM1)– and Orai1-deficient cells are resistant to oxidant stress. Functionally, oxidant-induced Ca2+ entry alters mitochondrial Ca2+ handling and bioenergetics and triggers cell death. STIM1 is S-glutathionylated at cysteine 56 in response to oxidant stress and evokes constitutive Ca2+ entry independent of intracellular Ca2+ stores. These experiments reveal that cysteine 56 is a sensor for oxidant-dependent activation of STIM1 and demonstrate a molecular link between oxidant stress and Ca2+ signaling via the CRAC channel. 相似文献
53.
Gallego Romero I Basu Mallick C Liebert A Crivellaro F Chaubey G Itan Y Metspalu M Eaaswarkhanth M Pitchappan R Villems R Reich D Singh L Thangaraj K Thomas MG Swallow DM Mirazón Lahr M Kivisild T 《Molecular biology and evolution》2012,29(1):249-260
Milk consumption and lactose digestion after weaning are exclusively human traits made possible by the continued production of the enzyme lactase in adulthood. Multiple independent mutations in a 100-bp region--part of an enhancer--approximately 14-kb upstream of the LCT gene are associated with this trait in Europeans and pastoralists from Saudi Arabia and Africa. However, a single mutation of purported western Eurasian origin accounts for much of observed lactase persistence outside Africa. Given the high levels of present-day milk consumption in India, together with archaeological and genetic evidence for the independent domestication of cattle in the Indus valley roughly 7,000 years ago, we sought to determine whether lactase persistence has evolved independently in the subcontinent. Here, we present the results of the first comprehensive survey of the LCT enhancer region in south Asia. Having genotyped 2,284 DNA samples from across the Indian subcontinent, we find that the previously described west Eurasian -13910 C>T mutation accounts for nearly all the genetic variation we observed in the 400- to 700-bp LCT regulatory region that we sequenced. Geography is a significant predictor of -13910*T allele frequency, and consistent with other genomic loci, its distribution in India follows a general northwest to southeast declining pattern, although frequencies among certain neighboring populations vary substantially. We confirm that the mutation is identical by descent to the European allele and is associated with the same>1 Mb extended haplotype in both populations. 相似文献
54.
Long-lasting siRNA-based down-regulation of gene of interest can be achieved by lentiviral-based expression vectors driving the production of short hairpin RNA (shRNA). We investigated an attractive therapeutic approach to target the expression of proinflammatory GMF by using lentiviral vector encoding GMF-specific shRNA to reduce GMF levels in the spinal cord and brain of mice. To determine the effect of GMF-shRNA on GMF protein levels, we performed quantitative ELISA analysis in brain and in thoracic, cervical and lumbar regions of spinal cord from mice followed by GMF-shRNA (G-shRNA) or control shRNA (C-shRNA) treatments. Our results show a marked reduction of GMF protein levels in brain and spinal cord of mice treated with GMF-shRNA compared to control shRNA treatment. Consistent with the GMF protein analysis, the immunohistochemical examination of the spinal cord sections of EAE mice treated with GMF-shRNA showed significantly reduced GMF-immunoreactivity. Thus, the down-regulation of GMF by GMF-shRNA was efficient and wide spread in CNS as evident by the significantly reduced levels of GMF protein in the brain and spinal cord of mice. 相似文献
55.
56.
MohanKumar K Kaza N Jagadeeswaran R Garzon SA Bansal A Kurundkar AR Namachivayam K Remon JI Bandepalli CR Feng X Weitkamp JH Maheshwari A 《American journal of physiology. Gastrointestinal and liver physiology》2012,303(1):G93-102
Necrotizing enterocolitis (NEC) is an inflammatory bowel necrosis of premature infants. In tissue samples of NEC, we identified numerous macrophages and a few neutrophils but not many lymphocytes. We hypothesized that these pathoanatomic characteristics of NEC represent a common tissue injury response of the gastrointestinal tract to a variety of insults at a specific stage of gut development. To evaluate developmental changes in mucosal inflammatory response, we used trinitrobenzene sulfonic acid (TNBS)-induced inflammation as a nonspecific insult and compared mucosal injury in newborn vs. adult mice. Enterocolitis was induced in 10-day-old pups and adult mice (n = 25 animals per group) by administering TNBS by gavage and enema. Leukocyte populations were enumerated in human NEC and in murine TNBS-enterocolitis using quantitative immunofluorescence. Chemokine expression was measured using quantitative polymerase chain reaction, immunoblots, and immunohistochemistry. Macrophage recruitment was investigated ex vivo using intestinal tissue-conditioned media and bone marrow-derived macrophages in a microchemotaxis assay. Similar to human NEC, TNBS enterocolitis in pups was marked by a macrophage-rich leukocyte infiltrate in affected tissue. In contrast, TNBS-enterocolitis in adult mice was associated with pleomorphic leukocyte infiltrates. Macrophage precursors were recruited to murine neonatal gastrointestinal tract by the chemokine CXCL5, a known chemoattractant for myeloid cells. We also demonstrated increased expression of CXCL5 in surgically resected tissue samples of human NEC, indicating that a similar pathway was active in NEC. We concluded that gut mucosal injury in the murine neonate is marked by a macrophage-rich leukocyte infiltrate, which contrasts with the pleomorphic leukocyte infiltrates in adult mice. In murine neonatal enterocolitis, macrophages were recruited to the inflamed gut mucosa by the chemokine CXCL5, indicating that CXCL5 and its cognate receptor CXCR2 merit further investigation as potential therapeutic targets in NEC. 相似文献
57.
Kumar MS Praveenkumar R Ilavarasi A Rajeshwari K Thajuddin N 《Biotechnology letters》2012,34(2):247-251
Cr(VI) at 2.5, 5, 7.5 and 10 mg/l was removed over 1–5 days by a freshwater cyanobacterium, Chroococcus sp. 2.5 mg Cr(VI)/l gave the optimum rate. With 5 mg Cr(VI)/l, activities of superoxide dismutase and catalase were increased.
Amounts of palmitic (16:0), stearic (18:0) and oleic acid (18:1) in the cell also increased after exposure to Cr(VI). 相似文献
58.
The formation of advanced glycation endproducts (AGEs) occurs in diverse settings such as diabetes, aging, renal failure,
inflammation and hypoxia. The chief cellular receptor for AGEs, RAGE, transduces the effects of AGEs via signal transduction,
at least in part via processes requiring the RAGE cytoplasmic domain binding partner, diaphanous-1 or mDia1. Data suggest
that RAGE perpetuates the inflammatory signals initiated by AGEs via multiple mechanisms. AGE–RAGE interaction stimulates
generation of reactive oxygen species and inflammation—mechanisms which enhance AGE formation. Further, recent data in type
1 diabetic kidney reveal that deletion of RAGE prevents methylglyoxal accumulation, at least in part via RAGE-dependent regulation
of glyoxalase-1, a major enzyme involved in methylglyoxal detoxification. Taken together, these considerations place RAGE
in the center of biochemical and molecular stresses that characterize the complications of diabetes and chronic disease. Stopping
RAGE-dependent signaling may hold the key to interrupting cycles of cellular perturbation and tissue damage in these disorders. 相似文献
59.
60.
Carolin Lau Emily R. Adkins Ramaraja P. Ramasamy Heather R. Luckarift Glenn R. Johnson Plamen Atanassov 《Liver Transplantation》2012,2(1):162-168
Multicopper oxidases, such as laccase or bilirubin oxidase, are known to reduce molecular oxygen at very high redox potentials, which makes them attractive biocatalysts for enzymatic cathodes in biological fuel cells. By designing an enzymatic gas‐diffusion electrode, molecular oxygen can be supplied through the gaseous phase, avoiding solubility and diffusion limitations typically associated with liquid electrolytes. In doing so, the current density of enzymatic cathodes can theoretically be enhanced. This publication presents a material study of carbon/Teflon composites that aim to optimize the functionality of the gas‐diffusion and catalytic layers for application in enzymatic systems. The modification of the catalytic layer with multiwalled carbon nanotubes, for example, creates the basis for stronger π–π stacking interactions through tethered enzymatic linkers, such as pyrenes or perylene derivates. Cyclic voltammograms show the effective direct electron contact of laccase with carbon nanotube‐modified electrodes via tethered crosslinking molecules as a model system. The polarization behavior of laccase‐modified gas‐diffusion electrodes reveals open‐circuit potentials of +550 mV (versus Ag/AgCl) and current densities approaching 0.5 mA cm2 (at zero potential) in air‐breathing mode. 相似文献