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341.
Constantinos D. Antoniadis Emiliana D'Oria Panagiotis G. Karamertzanis Derek A. Tocher Alastair J. Florence Sarah L. Price Alan G. Jones 《Chirality》2010,22(4):447-455
Following the computation of a lattice energy landscape which predicted that there should be more stable, denser forms of (R)‐1‐phenylethylammonium‐(S)‐2‐phenylbutyrate, crystallizations from a range of solvents were performed to search for other polymorphs and investigate the possibility that the known P41 structure could be a hydrate. Extensive crystallization experiments from a wide range of solvents gave fine needles or microcrystalline samples. A redetermination of the P41 structure by powder X‐ray diffraction located all protons, and in conjunction with other experimental and computational evidence showed that the structure was anhydrous. Evidence for two additional forms was found as mixtures with form I. These include an orthorhombic form, possibly a Z′ = 3 polymorph, and another as yet unidentified form obtained as a minor component from dichloromethane solution. However, both these forms appear to be metastable with respect to form I (P41), which is therefore probably the most thermodynamically stable form that can be crystallized from solution under ambient conditions. This determination of the solid state behavior of the less readily crystallized member of the diastereomeric salt system (R)‐1‐phenylethylammonium‐(R/S)‐2‐phenylbutyrate provides a challenge to the theoretical modeling to explain its ideal resolution behavior. Chirality 2010. © 2009 Wiley‐Liss, Inc. 相似文献
342.
A rise in intracellular calcium concentration ([Ca(2+)](i)) is necessary for platelet activation. A major component of the [Ca(2+)](i) elevation occurs through store-operated Ca(2+) entry (SOCE). The aim of this study was to understand the contribution of the classical PKC isoform, PKCα to platelet SOCE, using platelets from PKCα-deficient mice. SOCE was reduced by approximately 50% in PKCα(-/-) platelets, or following treatment with bisindolylmaleimide I, a PKC inhibitor. However, TG-induced Mn(2+) entry was unaffected, which suggests that divalent cation entry through store-operated channels is not directly regulated. Blocking the autocrine action of secreted ADP or 5-HT on its receptors did not reproduce the effect of PKCα deficiency. In contrast, SN-6, a Na(+)/Ca(2+) exchanger inhibitor, did reduce SOCE to the same extent as loss of PKCα, as did replacing extracellular Na(+) with NMDG(+). These treatments had no further effect in PKCα(-/-) platelets. These data suggest that PKCα enhances the extent of SOCE in mouse platelets by regulating Ca(2+) entry through the Na(+)/Ca(2+) exchanger. 相似文献
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344.
Donald AD Clark VL Patel S Day FA Rowlands MG Wibata J Stimson L Hardcastle A Eccles SA McNamara D Needham LA Raynaud FI Aherne W Moffat DF 《Bioorganic & medicinal chemistry letters》2010,20(22):6657-6660
Inhibition of histone deacetylase activity represents a promising new modality in the treatment of a number of cancers. A novel HDAC series demonstrating inhibitory activity in cell proliferation assays is described. Optimisation based on the introduction of basic amine linkers to effect good drug distribution to tumour led to the identification of a compound with oral activity in a human colon cancer xenograft study associated with increased histone H3 acetylation in tumour tissue. 相似文献
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346.
Cheryl-lynn Y Ong Scott A Beatson Makrina Totsika Christiane Forestier Alastair G McEwan Mark A Schembri 《BMC microbiology》2010,10(1):183
Background
Catheter-associated urinary tract infection (CAUTI) is the most common nosocomial infection in the United States and is caused by a range of uropathogens. Biofilm formation by uropathogens that cause CAUTI is often mediated by cell surface structures such as fimbriae. In this study, we characterised the genes encoding type 3 fimbriae from CAUTI strains of Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Citrobacter koseri and Citrobacter freundii. 相似文献347.
348.
Richard J. A. Goodwin Alastair M. Lang Heather Allingham Mats Borén Andrew R. Pitt 《Proteomics》2010,10(9):1751-1761
The effectiveness of rapid and controlled heating of intact tissue to inactivate native enzymatic activity and prevent proteome degradation has been evaluated. Mouse brains were bisected immediately following excision, with one hemisphere being heat treated followed by snap freezing in liquid nitrogen while the other hemisphere was snap frozen immediately. Sections were cut by cryostatic microtome and analyzed by MALDI‐MS imaging and minimal label 2‐D DIGE, to monitor time‐dependent relative changes in intensities of protein and peptide signals. Analysis by MALDI‐MS imaging demonstrated that the relative intensities of markers varied across a time course (0–5 min) when the tissues were not stabilized by heat treatment. However, the same markers were seen to be stabilized when the tissues were heat treated before snap freezing. Intensity profiles for proteins indicative of both degradation and stabilization were generated when samples of treated and nontreated tissues were analyzed by 2‐D DIGE, with protein extracted before and after a 10‐min warming of samples. Thus, heat treatment of tissues at the time of excision is shown to prevent subsequent uncontrolled degradation of tissues at the proteomic level before any quantitative analysis, and to be compatible with downstream proteomic analysis. 相似文献
349.
William W. Lockwood Raj Chari Bradley P. Coe Kelsie L. Thu Cathie Garnis Chad A. Malloff Jennifer Campbell Ariane C. Williams Dorothy Hwang Chang-Qi Zhu Timon P. H. Buys John Yee John C. English Calum MacAulay Ming-Sound Tsao Adi F. Gazdar John D. Minna Stephen Lam Wan L. Lam 《PLoS medicine》2010,7(7)
350.