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51.
Soyombo AA Tjon-Kon-Sang S Rbaibi Y Bashllari E Bisceglia J Muallem S Kiselyov K 《The Journal of biological chemistry》2006,281(11):7294-7301
Mucolipidosis type IV (MLIV) is caused by mutations in the ion channel mucolipin 1 (TRP-ML1). MLIV is typified by accumulation of lipids and membranous materials in intracellular organelles, which was hypothesized to be caused by the altered membrane fusion and fission events. How mutations in TRP-ML1 lead to aberrant lipolysis is not known. Here we present evidence that MLIV is a metabolic disorder that is not associated with aberrant membrane fusion/fission events. Thus, measurement of lysosomal pH revealed that the lysosomes in TRP-ML1(-/-) cells obtained from the patients with MLIV are over-acidified. TRP-ML1 can function as a H(+) channel, and the increased lysosomal acidification in TRP-ML1(-/-) cells is likely caused by the loss of TRP-ML1-mediated H(+) leak. Measurement of lipase activity using several substrates revealed a marked reduction in lipid hydrolysis in TRP-ML1(-/-) cells, which was rescued by the expression of TRP-ML1. Cell fractionation indicated specific loss of acidic lipase activity in TRP-ML1(-/-) cells. Furthermore, dissipation of the acidic lysosomal pH of TRP-ML1(-/-) cells by nigericin or chloroquine reversed the lysosomal storage disease phenotype. These findings provide a new mechanism to account for the pathogenesis of MLIV. 相似文献
52.
Duncton MA Piatnitski EL Katoch-Rouse R Smith LM Kiselyov AS Milligan DL Balagtas C Wong WC Kawakami J Doody JF 《Bioorganic & medicinal chemistry letters》2006,16(6):1579-1581
A novel class of 1-(isoquinolin-5-yl)-4-arylamino-phthalazines is described as inhibitors of vascular endothelial growth factor receptor II (VEGFR-2). Many compounds display VEGFR-2 inhibitory activity with an IC(50) as low as 0.017 microM in an HTRF enzymatic assay. The compounds also inhibit VEGFR-1, a related tyrosine kinase. 相似文献
53.
Kiselyov AS Semenova M Semenov VV Piatnitski E 《Bioorganic & medicinal chemistry letters》2006,16(6):1726-1730
Novel potent derivatives of (azol-1-yl)methyl-N-arylbenzamides with improved solubility (>3mM) are described as ATP-competitive inhibitors of vascular endothelial growth factor receptor 2 (VEGFR-2). Many compounds display VEGFR-2 inhibitory activity reaching IC(50)<100 nM in the enzymatic assay. The compounds also inhibit the related tyrosine kinase, VEGFR-1, with similar potencies. Several compounds containing bulky lipophilic substituents at the benzamide pharmacophore yielded 10- to 17-fold selectivity for the VEGFR-2 versus VEGFR-1 kinase. 相似文献
54.
ANDREA FERREIRA DA COSTA PABLO JOSÉ FRANCISCO PENA RODRIGUES MARIA DAS GRAÇAS LAPA WANDERLEY 《Botanical journal of the Linnean Society. Linnean Society of London》2009,159(1):163-181
The species related to Vriesea paraibica (Bromeliaceae, Tillandsioideae) have controversial taxonomic limits. For several decades, this group has been identified in herbarium collections as V. × morreniana, an artificial hybrid that does not grow in natural habitats. The aim of this study was to assess the morphological variation in the V. paraibica complex through morphometric analyses of natural populations. Two sets of analyses were performed: the first involved six natural populations (G1) and the second was carried out on taxa that emerged from the first analysis, but using material from herbarium collections (G2). Univariate ANOVA was used, as well as discriminant analysis of 16 morphometric variables in G1 and 18 in G2. The results of the analyses of the two groups were similar and led to the selection of diagnostic traits of four species. Lengths of the lower and median floral bracts were significant for the separation of red and yellow floral bracts. Vriesea paraibica and V. interrogatoria have red bracts; these two species are differentiated by the widths of the lower and median portions of the inflorescence and by scape length. These structures are larger in the former and smaller in the latter. Of the species with yellow floral bracts, V. eltoniana is distinguished by longer leaf blades and scapes and V. flava is characterized by its shorter sepal lengths. © 2009 The Linnean Society of London, Botanical Journal of the Linnean Society, 2009, 159 , 163–181. 相似文献
55.
Alexander S. Kiselyov Marina Semenova Victor V. Semenov 《Bioorganic & medicinal chemistry letters》2009,19(5):1344-1348
Derivatives of (1,2,3-triazol-4-yl)benzenamines are described as potent and ATP-competitive inhibitors of vascular endothelial growth factor receptors I and II (VEGFR-1/2). A number of compounds exhibited VEGFR-2 and VEGFR-1 inhibitory activity comparable to that of Vatalanib? in both HTRF enzymatic and cellular assays. 相似文献
56.
57.
YIT ARN TEH OLIVIER MAZÉAS ALYSSA R. ATWOOD TRIFFID ABEL ROBERT C. RHEW 《Global Change Biology》2009,15(2):330-345
The Arctic tundra has been shown to be a potentially significant regional sink for methyl chloride (CH3Cl) and methyl bromide (CH3Br), although prior field studies were spatially and temporally limited, and did not include gross flux measurements. Here we compare net and gross CH3Cl and CH3Br fluxes in the northern coastal plain and continental interior. As expected, both regions were net sinks for CH3Cl and CH3Br. Gross uptake rates (−793 nmol CH3Cl m−2 day−1 and −20.3 nmol CH3Br m−2 day−1) were 20–240% greater than net fluxes, suggesting that the Arctic is an even greater sink than previously believed. Hydrology was the principal regulator of methyl halide flux, with an overall trend towards increasing methyl halide uptake with decreasing soil moisture. Water table depth was one of the best predictors of net and gross uptake, with uptake increasing proportionately with water table depth. In drier areas, gross uptake was very high, averaging −1201 nmol CH3Cl m−2 day−1 and −34.9 nmol CH3Br m−2 day−1; in flooded areas, gross uptake was significantly lower, averaging −61 nmol CH3Cl m−2 day−1 and −2.3 nmol CH3Br m−2 day−1. Net and gross uptake was greater in the continental interior than in the northern coastal plain, presumably due to drier inland conditions. Within certain microtopographic features (low‐ and high‐centered polygons), uptake rates were positively correlated with soil temperature, indicating that temperature played a secondary role in methyl halide uptake. Incubations suggested that the inverse relationship between water content and methyl halide uptake was the result of mass transfer limitation in saturated soils, rather than because of reduced microbial activity under anaerobic conditions. These findings have potential regional significance, as the Arctic is expected to become warmer and drier due to anthropogenic climate forcing, potentially enhancing the Arctic sink for CH3Cl and CH3Br. 相似文献
58.
Research laboratories studying the genetics of companion animals have no database tools specifically designed to aid in the
management of the many kinds of data that are generated, stored and analyzed. We have developed a relational database, "DOG-SPOT,"
to provide such a tool. Implemented in MS-Access, the database is easy to extend or customize to suit a lab's particular needs.
With DOG-SPOT a lab can manage data relating to dogs, breeds, samples, biomaterials, phenotypes, owners, communications, amplicons,
sequences, markers, genotypes and personnel. Such an integrated data structure helps ensure high quality data entry and makes
it easy to track physical stocks of biomaterials and oligonucleotides. 相似文献
59.
60.
Homer binds TRPC family channels and is required for gating of TRPC1 by IP3 receptors 总被引:12,自引:0,他引:12
Yuan JP Kiselyov K Shin DM Chen J Shcheynikov N Kang SH Dehoff MH Schwarz MK Seeburg PH Muallem S Worley PF 《Cell》2003,114(6):777-789