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101.
Hiroaki Iwaki Stephan Grosse Hélène Bergeron Hannes Leisch Krista Morley Yoshie Hasegawa Peter C. K. Lau 《Applied and environmental microbiology》2013,79(10):3282-3293
Whereas the biochemical properties of the monooxygenase components that catalyze the oxidation of 2,5-diketocamphane and 3,6-diketocamphane (2,5-DKCMO and 3,6-DKCMO, respectively) in the initial catabolic steps of (+) and (−) isomeric forms of camphor (CAM) metabolism in Pseudomonas putida ATCC 17453 are relatively well characterized, the actual identity of the flavin reductase (Fred) component that provides the reduced flavin to the oxygenases has hitherto been ill defined. In this study, a 37-kDa Fred was purified from a camphor-induced culture of P. putida ATCC 17453 and this facilitated cloning and characterization of the requisite protein. The active Fred is a homodimer with a subunit molecular weight of 18,000 that uses NADH as an electron donor (Km = 32 μM), and it catalyzes the reduction of flavin mononucleotide (FMN) (Km = 3.6 μM; kcat = 283 s−1) in preference to flavin adenine dinucleotide (FAD) (Km = 19 μM; kcat = 128 s−1). Sequence determination of ∼40 kb of the CAM degradation plasmid revealed the locations of two isofunctional 2,5-DKCMO genes (camE25–1 for 2,5-DKCMO-1 and camE25–2 for 2,5-DKCMO-2) as well as that of a 3,6-DKCMO-encoding gene (camE36). In addition, by pulsed-field gel electrophoresis, the CAM plasmid was established to be linear and ∼533 kb in length. To enable functional assessment of the two-component monooxygenase system in Baeyer-Villiger oxidations, recombinant plasmids expressing Fred in tandem with the respective 2,5-DKCMO- and 3,6-DKCMO-encoding genes in Escherichia coli were constructed. Comparative substrate profiling of the isofunctional 2,5-DCKMOs did not yield obvious differences in Baeyer-Villiger biooxidations, but they are distinct from 3,6-DKCMO in the stereoselective oxygenations with various mono- and bicyclic ketone substrates. 相似文献
102.
Zhinxin Zhao Roberto Gambari Kenneth Ka-Ho Lee Stanton Hon-Lung Kok Raymond Siu-Ming Wong Fung-Yi Lau Johnny Cheuk-On Tang Kim-Hung Lam Chor-Hing Cheng Desmond Kwok Po Hau Chung-Hin Chui Wai-Yeung Wong Wai-Kwok Wong 《Bioorganic & medicinal chemistry letters》2013,23(8):2373-2376
We explore the possible cellular cytotoxic activity of an amphiphilic silicon(IV) phthalocyanine with axially ligated rhodamine B under ambient light experimental environment as well as its in vivo antitumour potential using Hep3B hepatoma cell model. After loading into the Hep3B hepatoma cells, induction of cellular cytotoxicity and cell cycle arrest were detected. Strong growth inhibition of tumour xenograft together with significant tumour necrosis and limited toxicological effects exerted on the nude mice could be identified. 相似文献
103.
Colin H. MacKinnon Kevin Lau Jason D. Burch Yuan Chen Jonathon Dines Xiao Ding Charles Eigenbrot Alexander Heifetz Allan Jaochico Adam Johnson Joachim Kraemer Susanne Kruger Thomas M. Krülle Marya Liimatta Justin Ly Rosemary Maghames Christian A.G.N. Montalbetti Daniel F. Ortwine Zhonghua Pei 《Bioorganic & medicinal chemistry letters》2013,23(23):6331-6335
Inhibition of the non-receptor tyrosine kinase ITK, a component of the T-cell receptor signalling cascade, may represent a novel treatment for allergic asthma. Here we report the structure-based optimization of a series of benzothiazole amides that demonstrate sub-nanomolar inhibitory potency against ITK with good cellular activity and kinase selectivity. We also elucidate the binding mode of these inhibitors by solving the X-ray crystal structures of several inhibitor-ITK complexes. 相似文献
104.
Chiou-Yeong Saw Tsai-Ju Chang Po-Ya Chen Fan-Jhen Dai Yie-Qie Lau Ting-Yu Chen 《Bioscience, biotechnology, and biochemistry》2013,77(12):2327-2333
ABSTRACTThis study was aimed to investigate the presence of Bacillus coagulans vegetative cells in the intestine and fecal samples in rats fed B. coagulans spores as well as to estimate the ratios of spores and vegetative cells in these samples. A two-step process has been developed to enumerate B. coagulans in different mixed bacterial samples, specifically (1) observation of yellow ring formation on modified GYEA medium upon incubation at 55°C, (2) microscopic examination of spore formation after 7 d of incubation. Our results have demonstrated the presence of vegetative cells in the intestinal and fecal samples in rats fed B. coagulans spores. The ratios of B. coagulans spores and vegetative cells in cecal fluid, colonic content, and feces were approximately 2:8, 2:8, and 4:6, respectively. The existence of B. coagulans vegetative cells improved the intestinal milieu through an elevated short-chain fatty acid concentrations, higher fecal moisture, and lower fecal pH. 相似文献
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107.
Yang Wang Xu Li Xiaoliang Wang Waynebond Lau Yajing Wang Yuan Xing Xing Zhang Xinliang Ma Feng Gao 《PloS one》2013,8(8)
Evidence suggests Ginsenoside Rd (GSRd), a biologically active extract from the medical plant Panax Ginseng, exerts antioxidant effect, decreasing reactive oxygen species (ROS) formation. Current study determined the effect of GSRd on myocardial ischemia/reperfusion (MI/R) injury (a pathological condition where ROS production is significantly increased) and investigated the underlying mechanisms. The current study utilized an in vivo rat model of MI/R injury and an in vitro neonatal rat cardiomyocyte (NRC) model of simulated ischemia/reperfusion (SI/R) injury. Infarct size was measured by Evans blue/TTC double staining. NRC injury was determined by MTT and lactate dehydrogenase (LDH) leakage assay. ROS accumulation and apoptosis were assessed by flow cytometry. Mitochondrial membrane potential (MMP) was determined by 5, 5′, 6, 6′-tetrachloro-1, 1′, 3, 3′-tetrathylbenzimidazol carbocyanine iodide (JC-1). Cytosolic translocation of mitochondrial cytochrome c and expression of caspase-9, caspase-3, Bcl-2 family proteins, and phosphorylated Akt and GSK-3β were determined by western blot. Pretreatment with GSRd (50 mg/kg) significantly augmented rat cardiac function, as evidenced by increased left ventricular ejection fraction (LVEF) and ±dP/dt. GSRd reduced myocardial infarct size, apoptotic cell death, and blood creatine kinase/lactate dehydrogenase levels after MI/R. In NRCs, GSRd (10 µM) inhibited SI/R-induced ROS generation (P<0.01), decreased cellular apoptosis, stabilized the mitochondrial membrane potential (MMP), and attenuated cytosolic translocation of mitochondrial cytochrome c. GSRd inhibited activation of caspase-9 and caspase-3, increased the phosphorylated Akt and GSK-3β, and increased the Bcl-2/Bax ratio. Together, these data demonstrate GSRd mediated cardioprotective effect against MI/R–induced apoptosis via a mitochondrial-dependent apoptotic pathway. 相似文献
108.
Critical Role of Grain Boundaries for Ion Migration in Formamidinium and Methylammonium Lead Halide Perovskite Solar Cells 下载免费PDF全文
109.
Early Weight Loss with Liraglutide 3.0 mg Predicts 1‐Year Weight Loss and is Associated with Improvements in Clinical Markers 下载免费PDF全文
110.
William Whittaker Laura Anselmi S?ren Rud Kristensen Yiu-Shing Lau Simon Bailey Peter Bower Katherine Checkland Rebecca Elvey Katy Rothwell Jonathan Stokes Damian Hodgson 《PLoS medicine》2016,13(9)
BackgroundHealth services across the world increasingly face pressures on the use of expensive hospital services. Better organisation and delivery of primary care has the potential to manage demand and reduce costs for hospital services, but routine primary care services are not open during evenings and weekends.Extended access (evening and weekend opening) is hypothesized to reduce pressure on hospital services from emergency department visits. However, the existing evidence-base is weak, largely focused on emergency out-of-hours services, and analysed using a before-and after-methodology without effective comparators.ConclusionsThe study found that extending access was associated with a reduction in emergency department visits in the first 12 months. The results of the research have already informed the decision by National Health Service England to extend primary care access across Greater Manchester from 2016. However, further evidence is needed to understand whether extending primary care access is cost-effective and sustainable. 相似文献