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51.
Kieran F. Scott Timothy J. Mann Shadma Fatima Mila Sajinovic Anshuli Razdan Ryung Rae Kim Adam Cooper Aflah Roohullah Katherine J. Bryant Kasuni K. Gamage David G. Harman Fatemeh Vafaee Garry G. Graham W. Bret Church Pamela J. Russell Qihan Dong Paul de Souza 《Molecules (Basel, Switzerland)》2021,26(23)
Phospholipase A2 (PLA2) enzymes were first recognized as an enzyme activity class in 1961. The secreted (sPLA2) enzymes were the first of the five major classes of human PLA2s to be identified and now number nine catalytically-active structurally homologous proteins. The best-studied of these, group IIA sPLA2, has a clear role in the physiological response to infection and minor injury and acts as an amplifier of pathological inflammation. The enzyme has been a target for anti-inflammatory drug development in multiple disorders where chronic inflammation is a driver of pathology since its cloning in 1989. Despite intensive effort, no clinically approved medicines targeting the enzyme activity have yet been developed. This review catalogues the major discoveries in the human group IIA sPLA2 field, focusing on features of enzyme function that may explain this lack of success and discusses future research that may assist in realizing the potential benefit of targeting this enzyme. Functionally-selective inhibitors together with isoform-selective inhibitors are necessary to limit the apparent toxicity of previous drugs. There is also a need to define the relevance of the catalytic function of hGIIA to human inflammatory pathology relative to its recently-discovered catalysis-independent function. 相似文献
52.
M. Tauhidul Islam Lachlan J. Tantau Nicholas A. Rae Zwi Barnea Chanh Q. Tran Christopher T. Chantler 《Journal of synchrotron radiation》2014,21(2):413-423
The X‐ray mass attenuation coefficients of silver were measured in the energy range 5–20 keV with an accuracy of 0.01–0.2% on a relative scale down to 5.3 keV, and of 0.09–1.22% on an absolute scale to 5.0 keV. This analysis confirms that with careful choice of foil thickness and careful correction for systematics, especially including harmonic contents at lower energies, the X‐ray attenuation of high‐Z elements can be measured with high accuracy even at low X‐ray energies (<6 keV). This is the first high‐accuracy measurement of X‐ray mass attenuation coefficients of silver in the low energy range, indicating the possibility of obtaining high‐accuracy X‐ray absorption fine structure down to the L1 edge (3.8 keV) of silver. Comparison of results reported here with an earlier data set optimized for higher energies confirms accuracy to within one standard error of each data set collected and analysed using the principles of the X‐ray extended‐range technique (XERT). Comparison with theory shows a slow divergence towards lower energies in this region away from absorption edges. The methodology developed can be used for the XAFS analysis of compounds and solutions to investigate structural features, bonding and coordination chemistry. 相似文献
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Christopher T. Chantler Nicholas A. Rae M. Tauhidul Islam Stephen P. Best Joey Yeo Lucas F. Smale James Hester Narges Mohammadi Feng Wang 《Journal of synchrotron radiation》2012,19(2):145-158
Methods for the quantification of statistically valid measures of the uncertainties associated with X‐ray absorption fine structure (XAFS) data obtained from dilute solutions using fluorescence measurements are developed. Experimental data obtained from 10 mM solutions of the organometallic compound ferrocene, Fe(C5H5)2, are analysed within this framework and, following correction for various electronic and geometrical factors, give robust estimates of the standard errors of the individual measurements. The reliability of the refinement statistics of standard current XAFS structure approaches that do not include propagation of experimental uncertainties to assess subtle structural distortions is assessed in terms of refinements obtained for the staggered and eclipsed conformations of the C5H5 rings of ferrocene. Standard approaches (XFIT, IFEFFIT) give refinement statistics that appear to show strong, but opposite, preferences for the different conformations. Incorporation of experimental uncertainties into an IFEFFIT‐like analysis yield refinement statistics for the staggered and eclipsed forms of ferrocene which show a far more realistic preference for the eclipsed form which accurately reflects the reliability of the analysis. Moreover, the more strongly founded estimates of the refined parameter uncertainties allow more direct comparison with those obtained by other techniques. These XAFS‐based estimates of the bond distances have accuracies comparable with those obtained using single‐crystal diffraction techniques and are superior in terms of their use in comparisons of experimental and computed structures. 相似文献
55.
SK Das CS Lim SY Yang JH Han BR Cho 《Chemical communications (Cambridge, England)》2012,48(67):8395-8397
We report a two-photon probe (FS1) which shows a 21-fold two-photon excited fluorescence enhancement in response to H(2)S and can selectively detect H(2)S in a rat hippocampal slice at a depth of 90-190 μm by using two-photon microscopy. 相似文献
56.
Eun Won Seo Ji Hee Han Cheol Ho Heo Prof. Dr. Jae Ho Shin Prof. Dr. Hwan Myung Kim Prof. Dr. Bong Rae Cho 《Chemistry (Weinheim an der Bergstrasse, Germany)》2012,18(39):12388-12394
Two‐photon microscopy (TPM) has become an indispensable tool in the study of biology and medicine due to the capability of this method for molecular imaging deep inside intact tissues. For the maximum utilization of TPM, a variety of two‐photon (TP) probes for specific applications are needed. In this article, we report a small‐molecule TP probe (ANO1) for nitric oxide (NO) that shows a rapid and specific NO response, a 68‐fold fluorescence enhancement in response to NO, and a maximum TP‐action cross‐section of 170 GM (GM: 10?50 cm4 photon?1) upon reaction with excess NO. This probe can be easily loaded into cells and tissues and can real‐time monitor NO in living tissues at 100–180 μm depth for longer than 1200 s through the use of TPM, with minimum interference from other biologically relevant species. 相似文献
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59.
H. A. Oelkers W. Raetz K. Reintelen P. Fleischmann W. Peyer F. Gstirner S. Krishna T. P. Ghose N. Rusting C. A. Rojahn F. Struffmann L. Ekkert L. Rosenthaler J. Rae und S. A. Celsi 《Fresenius' Journal of Analytical Chemistry》1934,97(3-4):145-148
Ohne Zusammenfassung 相似文献
60.
Two broad resonances at 9.33 MeV and 9.65 MeV are observed in the inelastic excitation of 18O on a 12C target at a laboratory energy of 82 MeV. The α-decay of these states has been measured. A coherent sum of Jπ = 2+ and 3? is required to fit the correlations. The structure of these states and the excitation mechanism is discussed. 相似文献