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921.
Massimo Gianotti Corrado Corti Sonia Delle Fratte Romano Di Fabio Colin P. Leslie Francesca Pavone Laura Piccoli Luigi Stasi Mark J. Wigglesworth 《Bioorganic & medicinal chemistry letters》2010,20(17):5069-5073
A novel imidazobenzazepine template (5a) with potent dual H1/5-HT2A antagonist activity was identified. Application of a zwitterionic approach to this poorly selective and poorly developable starting point successfully delivered a class of high quality leads, 3-[4-(3-R1-2-R-5H-imidazo[1,2-b][2]benzazepin-11-yl)-1-piperazinyl]-2,2-dimethylpropanoic acids (e.g., 9, 19, 20, and 21), characterized by potent and balanced H1/5-HT2A receptor antagonist activities and good developability profiles. 相似文献
922.
Elise Isabel Kevin P. Bateman Nathalie Chauret Wanda Cromlish Sylvie Desmarais Le T. Duong Jean-Pierre Falgueyret Jacques Yves Gauthier Sonia Lamontagne Cheuk K. Lau Serge Léger Tammy LeRiche Jean-François Lévesque Chun Sing Li Frédéric Massé Daniel J. McKay Christophe Mellon Deborah A. Nicoll-Griffith Renata M. Oballa M. David Percival W. Cameron Black 《Bioorganic & medicinal chemistry letters》2010,20(3):887-892
MK-0674 is a potent and selective cathepsin K inhibitor from the same structural class as odanacatib with a comparable inhibitory potency profile against Cat K. It is orally bioavailable and exhibits long half-life in pre-clinical species. In vivo studies using deuterated MK-0674 show stereoselective epimerization of the alcohol stereocenter via an oxidation/reduction cycle. From in vitro incubations, two metabolites could be identified: the hydroxyleucine and the glucuronide conjugate which were confirmed using authentic synthetic standards. 相似文献
923.
Sonia Gómez-Galera Eduard Rojas Duraialagaraja Sudhakar Changfu Zhu Ana M. Pelacho Teresa Capell Paul Christou 《Transgenic research》2010,19(2):165-180
Staple food crops, in particular cereal grains, are poor sources of key mineral nutrients. As a result, the world’s poorest
people, generally those subsisting on a monotonous cereal diet, are also those most vulnerable to mineral deficiency diseases.
Various strategies have been proposed to deal with micronutrient deficiencies including the provision of mineral supplements,
the fortification of processed food, the biofortification of crop plants at source with mineral-rich fertilizers and the implementation
of breeding programs and genetic engineering approaches to generate mineral-rich varieties of staple crops. This review provides
a critical comparison of the strategies that have been developed to address deficiencies in five key mineral nutrients—iodine,
iron, zinc, calcium and selenium—and discusses the most recent advances in genetic engineering to increase mineral levels
and bioavailability in our most important staple food crops. 相似文献
924.
Background
Taurine and zinc exert neurotrophic effects in the central nervous system. Current studies demonstrate that Na+/Cl- dependent neurotransmitter transporters, similar to that of taurine, are modulated by micromolar concentrations of zinc. This study examined the effect of zinc sulfate ex vivo on [3H]taurine transport in goldfish retina.Methods
Isolated cells were incubated in Ringer with zinc (0.1–100 µM). Taurine transport was done with 50 nM [3H]taurine or by isotopic dilution with taurine (0.001–1 mM) and 50 nM [3H]taurine.Results
Zinc reduced the capacity of taurine transport without changes in affinity, and caused a noncompetitive inhibition of high affinity taurine transport, with an EC50= 0.072 µM. The mechanism by which zinc affects taurine transport is unknown at the present.Conclusions
There may be a binding site of zinc in the transporter that affects union or translocation of taurine, or possibly the formation of taurine-zinc complexes, rather than free zinc, could affect the operation of the transporter.925.
926.
Duong Thi Huong Giang Edilbert Van Driessche Isabel Vandenberghe Bart Devreese Sonia Beeckmans 《Fish & shellfish immunology》2010,28(5-6):743-753
From the serum of Pangasianodon hypophthalmus, two proteins were isolated by affinity chromatography on Sepharose and phosphorylcholine–Sepharose. Their binding on the affinity matrices critically depends on the presence of Ca2+ ions. N-terminal sequencing and sequencing of internal tryptic peptides identified the proteins as pentraxins and from their binding properties they are identified as SAP (serum amyloid P component) and CRP (C-reactive protein). Per ml serum, 36 μg SAP and 56 μg CRP was purified. Upon gel filtration, both the SAP and CRP elute as trimers of respectively 24 kDa and 28 kDa subunits. Both proteins are devoid of inter-chain disulfide bonds. Both SAP and CRP are glycosylated and agglutinate rabbit erythrocytes and pathogenic bacteria Edwardsiella ictaluri and Aeromonas hydrophila, but not Micrococcus lysodeikticus or Escherichia coli. Haemagglutination of SAP and CRP is inhibited by galactose (MIC = 1 mM) and by phosphorylcholine (MIC = 1–2 mM), respectively. Circular dichroism studies revealed that antiparallel β-pleated sheets are dominating the secondary structure. Upon removing the Ca2+ ions by EDTA, slight structural changes are observed by CD spectroscopy in the near-UV region. Immunodiffusion shows that P. hypophthalmus SAP and CRP do not cross-react. 相似文献
927.
Arianna Tavanti Lambert AM Hensgens Selene Mogavero László Majoros Sonia Senesi Mario Campa 《BMC microbiology》2010,10(1):203
Background
Candida parapsilosis is known to show limited genetic variability, despite different karyotypes and phenotypes have been described. To further investigate this aspect, a collection of 62 sensu strictu C. parapsilosis independent isolates from 4 geographic regions (Italy, n = 19; New Zealand, n = 15; Argentina, n = 14; and Hungary, n = 14) and different body sites (superficial and deep seated) were analysed for their genetic and phenotypic traits. Amplification fragment length polymorphism (AFLP) analysis was used to confirm species identification and to evaluate intraspecific genetic variability. Phenotypic characterisation included clinically relevant traits, such as drug susceptibility, in vitro biofilm formation and aspartyl protease secretion. 相似文献928.
Natacha Olieric Melanie Kuchen Sandro Wagen Marion Sauter Stephanie Crone Sonia Edmondson Daniel Frey Christian Ostermeier Michel O Steinmetz Rolf Jaussi 《BMC biotechnology》2010,10(1):56
Background
Molecular DNA cloning is crucial to many experiments and with the trend to higher throughput of modern approaches automated techniques are urgently required. We have established an automated, fast and flexible low-cost expression cloning approach requiring only vector and insert amplification by PCR and co-transformation of the products. 相似文献929.
Miriam Bellido Laura Lugo Jorge A Roman-Blas Santos Castañeda Jose R Caeiro Sonia Dapia Emilio Calvo Raquel Largo Gabriel Herrero-Beaumont 《Arthritis research & therapy》2010,12(4):R152-11
Introduction
Osteoporosis (OP) increases cartilage damage in a combined rabbit model of OP and osteoarthritis (OA). Accordingly, we assessed whether microstructure impairment at subchondral bone aggravates cartilage damage in this experimental model. 相似文献930.
Libersou S Albertini AA Ouldali M Maury V Maheu C Raux H de Haas F Roche S Gaudin Y Lepault J 《The Journal of cell biology》2010,191(1):199-210
The entry of enveloped viruses into cells requires the fusion of viral and cellular membranes, driven by conformational changes in viral glycoproteins. Many studies have shown that fusion involves the cooperative action of a large number of these glycoproteins, but the underlying mechanisms are unknown. We used electron microscopy and tomography to study the low pH-induced fusion reaction catalyzed by vesicular stomatitis virus glycoprotein (G). Pre- and post-fusion crystal structures were observed on virions at high and low pH, respectively. Individual fusion events with liposomes were also visualized. Fusion appears to be driven by two successive structural rearrangements of G at different sites on the virion. Fusion is initiated at the flat base of the particle. Glycoproteins located outside the contact zone between virions and liposomes then reorganize into regular arrays. We suggest that the formation of these arrays, which have been shown to be an intrinsic property of the G ectodomain, induces membrane constraints, achieving the fusion reaction. 相似文献