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Photodynamic therapy (PDT) is a treatment combining a photosensitiser, molecular oxygen and visible light of characteristic wavelength to produce cytotoxic reactive oxygen species (ROS). Within our centre, a series of phenothiazinium salts were synthesised and initial characterisation studies performed to determine any potential use for PDT. All photosensitisers within the series were shown to have useful spectral properties for PDT, with absorbance lambdamax above 667 nm. The Log P values of the compounds were shown to range from -0.9 to > +2.0. Furthermore, Log P values were shown to be important in determining the site of subcellular localisation and as such the site of photooxidative damage. Derivatives with a Log P value of greater than +1.0 were shown to initially localise to the lysosomes then relocalise throughout the cytoplasm following illumination, whereas compounds with intermediate Log P values (-0.7 to +1.0) all remained lysosomal. Only methylene blue (Log P-0.9) was shown to redistribute to the nucleus upon illumination. Following treatment of RIF-1 cells with each phenothiazinium salt for 1 h and subsequent exposure to 665 nm laser light at a fluence rate of 10 mW cm(-2)(18 J cm(-2)), it was determined that the most potent photosensitiser was 260-fold more potent than methylene blue. Furthermore, the PDT efficacy of the photosensitisers was shown to be related to the level of mitochondrial damage induced directly following illumination.  相似文献   
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Spider Lamb Syndrome (SLS) is a semi-lethal congenital disorder, causing severe skeletal abnormalities in sheep. The syndrome has now been disseminated into several sheep breeds in the United States, Canada, and Australia. The mode of inheritance for SLS is autosomal recessive, making the identification and culling of carrier animals difficult due to their normal phenotype. Two large pedigrees segregating for the SLS mutation were established, and a genome scan with genetic markers from previously published genome maps of cattle and sheep was used to map the locus causing SLS. Genetic linkage between SLS and several microsatellite markers, OarJMP8, McM214, OarJMP12, and BL1038, was detected, thereby mapping the SLS locus to the telomeric end of ovine Chromosome (Chr) 6. Alignment of ovine Chr 6 with its evolutionary ortholog, human Chr 4, revealed a positional candidate gene, fibroblast growth factor receptor 3 (FGFR3). Received: 10 June 1998 / Accepted: 23 September 1998  相似文献   
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Secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein that inhibits cellular adhesion and proliferation. In this study, we report the detection of SPARC in the interphase nuclei of embryonic chicken cells in vivo. Differential partitioning of SPARC was also noted in the cytoplasm of these cells during discrete stages of M-phase: cells in metaphase and anaphase exhibited strong cytoplasmic immunoreactivity, whereas cells in telophase were devoid of labeling. Immunocytochemical analysis of embryonic chicken cells in vitro likewise showed the presence of SPARC in the nucleus. Furthermore, elution of soluble proteins and DNA from these cells indicated that SPARC might be a component of the nuclear matrix. We subsequently examined cultured bovine aortic endothelial cells, which initially appeared to express SPARC only in the cytoplasm. However, after elution of soluble proteins and chromatin, we also detected SPARC in the nuclear matrix of these cells. Embryonic chicken cells incubated with recombinant SPARC were seen to take up the protein and to translocate it to the nucleus progressively over a period of 17 h. These observations provide new information about SPARC, generally recognized as a secreted glycoprotein that mediates interactions between cells and components of the extracellular matrix. The evidence presented in this study indicates that SPARC might subserve analogous functions in the nuclear matrix.  相似文献   
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1-Hydroxycyclopropane carboxylic acid phosphate has been synthesized from diethyl succinate by acyloin condensation followed by ring contraction and phosphorylation. This compound is a potent competitive inhibitor of enzymes utilizing phosphoenolpyruvate. For phosphoenolpyruvate from maize, Ki = 7.3 μM at pH 8.0 in the presence of Mg2+. For pyruvate kinase, Ki = 2.0 mM at pH 7.0. For enolase, Ki = 8.0 μM at pH 8.0. In each case, this compound is a substantially better inhibitor than the commonly used phosphoenolpyruvate analogs phosphoglycolate and phospholactate, presumably because of the similarity in geometric and electronic structure between the cyclopropane compound and phosphoenolpyruvate.  相似文献   
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We measured the size of eggs produced by populations of Drosophila melanogaster that had been collected along latitudinal gradients in different continents or that had undergone several years of culture at different temperatures in the laboratory. Australian and South American populations from higher latitudes produced larger eggs when all were compared at a standard temperature. Laboratory populations that had been evolving at 16.5°C produced larger eggs than populations that had evolved at 25°C or 29°C, suggesting that temperature may be an important selective agent in producing the latitudinal clines. Flies from laboratory populations produced larger eggs at an experimental temperature of 16.5°C than at 25°C, and there was no indication of genotype-environment interaction for egg size. Evolution of egg size in response to temperature cannot be accounted for by differences in adult body size between populations. It is not clear which life-history traits are direct targets of thermal selection and which are showing correlated responses, and disentangling these is a task for the future.  相似文献   
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