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1.
Steyn SJ Pieterse DJ Mienie LJ Van der Schyf CJ 《Journal of biochemical and biophysical methods》2005,62(1):25-40
Most mitochondria-based methods used to investigate toxins require the use of relatively large amounts of material and hence compromised sensitivity in assay. We adopted procedures from methods initially developed to diagnose mitochondrial encephalomyopathies and unified these into a single assay. Eukaryotic cell membranes are selectively permeabilized with digitonin to render a system in which mitochondrial respiration can be measured rapidly and with considerable sensitivity. Mitochondria remain intact, uninjured, and in their natural environment where mitochondrial respiration can be measured in situ under physiologically relevant conditions. This approach furthermore allows measurement of toxin effects on individual mitochondrial complexes. Numerous compounds at varying concentrations can be screened for mitochondrial toxicity, while the site of mitochondrial inhibition can be determined simultaneously. We used this assay to investigate, in murine neuroblastoma (N-2alpha) cells, the mitochondrial inhibitory properties of the parkinsonian-inducing proneurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), and its neurotoxic monoamine oxidase-B (MAO-B)-generated metabolite, the 1-methyl-4-phenylpyridinium species (MPP(+)). Within the time frame of each measurement (15 min), MPTP (< or = 1 mM) did not interfere with in situ mitochondrial respiration. As expected, MPP(+) was found to be a potent Complex I inhibitor but surprisingly also found to inhibit Complex IV. Optimized conditions for performing this assay are provided. 相似文献
2.
Lippa B Kauffman GS Arcari J Kwan T Chen J Hungerford W Bhattacharya S Zhao X Williams C Xiao J Pustilnik L Su C Moyer JD Ma L Campbell M Steyn S 《Bioorganic & medicinal chemistry letters》2007,17(11):3081-3086
The synthesis and biological evaluation of potent and selective inhibitors of the erbB2 kinase is presented. Based on the 4-anilinoquinazoline chemotype, the syntheses of several new series of erbB2 inhibitors are described with quinazoline and pyrido[4,3-d]pyrimidine cores. The vast majority of these compounds are found to be >100x selective over the closely related EGFR kinase. Two lead compounds are further shown to have low clearance and moderate bioavailability in rat. 相似文献
3.
Stefanus Otto 《Inorganica chimica acta》2010,363(13):3316-3320
The substitution behaviour of [PtCl(R)(COD)] (R− = Me and Fc) complexes, by the stepwise addition of phosphine ligands, L (L = PPh3, PEt3 and P(NMe2)3), were investigated in situ by 1H and 31P NMR spectroscopy. Addition of less than two equivalents of the phosphine ligand results in the formation of dimeric molecules with the general formula trans-[Pt(R)(μ-Cl)(L)]2 for the sterically demanding systems where R− = Me/L = P(NMe2)3 and R− = Fc/L = PEt3, PPh3 and P(NMe2)3 while larger quantities resulted in cis- and trans mixtures of mononuclear complexes being formed. In the case of the relatively small steric demanding, strongly coordinating, PEt3 ligand the trans-[PtCl(R)(PEt3)2] mononuclear complexes were exclusively observed in both cases. The crystal structures of the two substrates, [PtCl(R)(COD)] (R− = Me or Fc), as well as the cis-[PtCl(Fc)(PPh3)2] substitution product are reported. 相似文献
4.
Jeanet ConradieGert J. Lamprecht Stefanus OttoJannie C. Swarts 《Inorganica chimica acta》2002,328(1):191-203
The synthesis of new β-diketonato rhodium(I) complexes of the type [Rh(FcCOCHCOR)(CO)2] and [Rh(FcCOCHCOR)(CO)(PPh3)] with Fc=ferrocenyl and R=Fc, C6H5, CH3 and CF3 are described. 1H, 13C and 31P NMR data showed that for each of the non-symmetric β-diketonato mono-carbonyl rhodium(I) complexes, two isomers exist in solution. The equilibrium constant, Kc, which relates these two isomers in an equilibrium reaction, are concentration independent but temperature and solvent dependent. ΔrG, ΔrH and ΔrS values for this equilibrium have been determined and a linear relationship between solvent polarity on the Dimroth scale and Kc exists. The relationship between RhP bond lengths, d(RhP), and 31P NMR peak positions as well as coupling constants 1J(31P103Rh) has been quantified to allow calculation of approximate d(RhP) values. Variations in d(RhP) for [Rh(RCOCHCOR′)(CO)(PPh3)] complexes have also been related to the group electronegativities (Gordy scale) of the terminal β-diketonato R groups trans to PPh3. A measure of the electron density on the rhodium centre of [Rh(RCOCHCOR′)(CO)(PPh3)] may be expressed in terms of the IR carbonyl stretching wave number, ν(CO), the sum of the group electronegativities of the R and R′ groups, (χR+χR′), or the observed pKa′ values of the free β-diketones RCOCH2COR′. An empirical relationship between ν(CO) and either pKa′ or (χR+χR′) has also been quantified. 相似文献
5.
New tricks of an old pattern: structural versatility of scorpion toxins with common cysteine spacing
Saucedo AL Flores-Solis D Rodríguez de la Vega RC Ramírez-Cordero B Hernández-López R Cano-Sánchez P Noriega Navarro R García-Valdés J Coronas-Valderrama F de Roodt A Brieba LG Domingos Possani L del Río-Portilla F 《The Journal of biological chemistry》2012,287(15):12321-12330
Scorpion venoms are a rich source of K(+) channel-blocking peptides. For the most part, they are structurally related small disulfide-rich proteins containing a conserved pattern of six cysteines that is assumed to dictate their common three-dimensional folding. In the conventional pattern, two disulfide bridges connect an α-helical segment to the C-terminal strand of a double- or triple-stranded β-sheet, conforming a cystine-stabilized α/β scaffold (CSα/β). Here we show that two K(+) channel-blocking peptides from Tityus scorpions conserve the cysteine spacing of common scorpion venom peptides but display an unconventional disulfide pattern, accompanied by a complete rearrangement of the secondary structure topology into a CS helix-loop-helix fold. Sequence and structural comparisons of the peptides adopting this novel fold suggest that it would be a new elaboration of the widespread CSα/β scaffold, thus revealing an unexpected structural versatility of these small disulfide-rich proteins. Acknowledgment of such versatility is important to understand how venom structural complexity emerged on a limited number of molecular scaffolds. 相似文献
6.
A large‐area,spatially continuous assessment of land cover map error and its impact on downstream analyses 下载免费PDF全文
Lyndon Estes Peng Chen Stephanie Debats Tom Evans Stefanus Ferreira Tobias Kuemmerle Gabrielle Ragazzo Justin Sheffield Adam Wolf Eric Wood Kelly Caylor 《Global Change Biology》2018,24(1):322-337
Land cover maps increasingly underlie research into socioeconomic and environmental patterns and processes, including global change. It is known that map errors impact our understanding of these phenomena, but quantifying these impacts is difficult because many areas lack adequate reference data. We used a highly accurate, high‐resolution map of South African cropland to assess (1) the magnitude of error in several current generation land cover maps, and (2) how these errors propagate in downstream studies. We first quantified pixel‐wise errors in the cropland classes of four widely used land cover maps at resolutions ranging from 1 to 100 km, and then calculated errors in several representative “downstream” (map‐based) analyses, including assessments of vegetative carbon stocks, evapotranspiration, crop production, and household food security. We also evaluated maps’ spatial accuracy based on how precisely they could be used to locate specific landscape features. We found that cropland maps can have substantial biases and poor accuracy at all resolutions (e.g., at 1 km resolution, up to ~45% underestimates of cropland (bias) and nearly 50% mean absolute error (MAE, describing accuracy); at 100 km, up to 15% underestimates and nearly 20% MAE). National‐scale maps derived from higher‐resolution imagery were most accurate, followed by multi‐map fusion products. Constraining mapped values to match survey statistics may be effective at minimizing bias (provided the statistics are accurate). Errors in downstream analyses could be substantially amplified or muted, depending on the values ascribed to cropland‐adjacent covers (e.g., with forest as adjacent cover, carbon map error was 200%–500% greater than in input cropland maps, but ~40% less for sparse cover types). The average locational error was 6 km (600%). These findings provide deeper insight into the causes and potential consequences of land cover map error, and suggest several recommendations for land cover map users. 相似文献
7.
de Roodt AR Estévez J Dolab JA Manzanelli MV Piñeiro N Paniagua JF Vogt AU 《Revista de biología tropical》2006,54(3):889-901
Bothrops cotiara is a venomous snake sporadically found in the province of Misiones in Argentina, South of Brazil and Paraguay. Data on the clinics of the envenomation produced by its bite and on its venom are scarce. There is no information on the neutralizing capacity of the antivenoms available. In this study, the lethal potency, hemorrhagic, necrotizing, coagulant and thrombin-like, defibrinogenating, indirect hemolytic and fibrinolytic activities of the venom of B. cotiara specimens from the province of Misiones were determined. The toxic activities were within the range of those described for the other Bothrops species from Argentina, and the electrophoretic and chromatographic studies showed similarities with those described for the other bothropic venoms. The immunochemical reactivity of six South American anti Viper antivenoms (ELISA) have a strong reactivity with all the antivenoms studied. The neutralizing capacity of three of these therapeutic antivenoms against the lethal potency and hemorrhagic, necrotizing, coagulant, thrombin-like and hemolytic activities showed a very close neutralizing capacity. Our data strongly suggest that the antivenoms for therapeutic use available in this area of South America are useful to neutralize the toxic and enzymatic activities of the venom of this uncommon specie of Bothrops. 相似文献
8.
Steffen Fritz Linda See Ian McCallum Liangzhi You Andriy Bun Elena Moltchanova Martina Duerauer Fransizka Albrecht Christian Schill Christoph Perger Petr Havlik Aline Mosnier Philip Thornton Ulrike Wood‐Sichra Mario Herrero Inbal Becker‐Reshef Chris Justice Matthew Hansen Peng Gong Sheta Abdel Aziz Anna Cipriani Renato Cumani Giuliano Cecchi Giulia Conchedda Stefanus Ferreira Adriana Gomez Myriam Haffani Francois Kayitakire Jaiteh Malanding Rick Mueller Terence Newby Andre Nonguierma Adeaga Olusegun Simone Ortner D. Ram Rajak Jansle Rocha Dmitry Schepaschenko Maria Schepaschenko Alexey Terekhov Alex Tiangwa Christelle Vancutsem Elodie Vintrou Wu Wenbin Marijn van der Velde Antonia Dunwoody Florian Kraxner Michael Obersteiner 《Global Change Biology》2015,21(5):1980-1992
A new 1 km global IIASA‐IFPRI cropland percentage map for the baseline year 2005 has been developed which integrates a number of individual cropland maps at global to regional to national scales. The individual map products include existing global land cover maps such as GlobCover 2005 and MODIS v.5, regional maps such as AFRICOVER and national maps from mapping agencies and other organizations. The different products are ranked at the national level using crowdsourced data from Geo‐Wiki to create a map that reflects the likelihood of cropland. Calibration with national and subnational crop statistics was then undertaken to distribute the cropland within each country and subnational unit. The new IIASA‐IFPRI cropland product has been validated using very high‐resolution satellite imagery via Geo‐Wiki and has an overall accuracy of 82.4%. It has also been compared with the EarthStat cropland product and shows a lower root mean square error on an independent data set collected from Geo‐Wiki. The first ever global field size map was produced at the same resolution as the IIASA‐IFPRI cropland map based on interpolation of field size data collected via a Geo‐Wiki crowdsourcing campaign. A validation exercise of the global field size map revealed satisfactory agreement with control data, particularly given the relatively modest size of the field size data set used to create the map. Both are critical inputs to global agricultural monitoring in the frame of GEOGLAM and will serve the global land modelling and integrated assessment community, in particular for improving land use models that require baseline cropland information. These products are freely available for downloading from the http://cropland.geo-wiki.org website. 相似文献
9.
The cloning and sequencing of the UDP-galactose 4-epimerase gene (galE) from Avibacterium paragallinarum. 总被引:1,自引:0,他引:1
The putative uridine diphosphate (UDP)-galactose 4-epimerase encoding gene, galE, was isolated from Avibacterium paragallinarum with the use of degenerate primers, colony hybridization and inverse PCR. The data revealed an open reading frame of 1017 bp encoding a protein of 338 amino acids with a molecular weight of 37 kDa and an isoelectric point of 5.5. High sequence homology was obtained with an 87, 91 and 89% sequence identity on protein level towards the galE genes from Actinobacillus pleuropneumoniae, Haemophilus influenza and Pasteurella multocida, respectively. To verify that the cloned galE gene encodes for a UDP-galactose 4-epimeras, this gene was cloned into the pYES-2 expression vector, followed by transformation in a Saccharomyces cerevisiae gal10 deletion strain. Complementation of the gal10 deletion mutant with the galE gene confirmed that this gene encodes a UDP-galactose 4-epimerase. 相似文献
10.
The cis effects of phosphine, arsine and stibine ligands have been evaluated by measuring the IR stretching frequency in dichloromethane of the carbonyl ligand in a series of Rh(I) Vaska-type complexes, trans-[RhCl(CO)(L)2]. These data were correlated with those obtained by Tolman for the electronic trans influences in the [Ni(L)(CO)3] complexes. The electronic contribution, χFc, of ferrocenyl was determined as 0.8 from these plots by evaluating PPh2Fc as ligand. In order to accommodate arsine and stibine ligands an additional correction term, to compensate for differences in the donor atom, was added to Tolman’s equation for calculation of the Tolman electronic parameter of phosphine ligands. In the resulting equation: ν(CONi)=2056.1+∑i=13χi+CL values for CL of CP=0, CAs=−1.5 and CSb=−3.1 are suggested for phosphine, arsine and stibine ligands, respectively. The crystal and molecular structures of trans-[RhCl(CO)(PPh2Fc)2] · 2C6H6, trans-[RhCl(CO){P(NMe2)3}2] and trans-[RhCl(CO)(AsPh3)2] are reported. The Tolman cone angles for PPh2Fc and P(NMe2)3 were determined as 169° and 166°, while the effective cone angles for PPh2Fc, P(NMe2)3 and AsPh3 were determined as 171°, 168° and 147°, respectively. 相似文献