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61.
Paschke R Kalbitz J Paetz C Luckner M Mueller T Schmoll HJ Mueller H Sorkau E Sinn E 《Journal of inorganic biochemistry》2003,94(4):335-342
This report continues our work on new compounds which consist of three functional parts--a transport fragment, a spacer and a biologically active 'drug' component. Here cholic acid functions as the transport fragment, linked via an alkyl spacer to a carboplatin analog, representing the drug (carbo-ChAPt-Fig. 1). We describe the synthesis and characterization of the series of complexes [Pt(Cyclobutane-1,1-dicarboxylato)(diamine)], [diamine=CholCOO(CH(2))(n)CH(CH(2)NH(2))(2) and THP(CH(2))(n)CH-(CH(2)NH(2))(2), n=4, 6, 8, 11]. The compounds were characterized by elemental analysis and NMR-measurements. Cytostatic activity data are given. In general, the cytostatic activity is similar to that of the parent compound and is strongly influenced by the length of the alkyl chain spacer separating the drug and transport fragments, the ones with long chain spacers being more toxic than the parent complexes. Preliminary investigations indicate the ability of the ChAPt to break resistance of tumor cells against common platinum tumor drugs, e.g. cisplatin. They are effective even on cell lines that have developed resistance to other drugs such as cis- and carboplatin. They are more cytotoxic so they are potentially effective at lower dose concentrations. The mode of cell death was examined by trypan-blue exclusion test and DNA gelelectrophoresis. Typical fragmentation of DNA was observed and the cells were still able to exclude trypan-blue. 相似文献
62.
Purification of the Pyruvate Dehydrogenase Multienzyme Complex of Zymomonas mobilis and Identification and Sequence Analysis of the Corresponding Genes 总被引:1,自引:0,他引:1
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Ute Neveling Ralf Klasen Stephanie Bringer-Meyer Hermann Sahm 《Journal of bacteriology》1998,180(6):1540-1548
The pyruvate dehydrogenase (PDH) complex of the gram-negative bacterium Zymomonas mobilis was purified to homogeneity. From 250 g of cells, we isolated 1 mg of PDH complex with a specific activity of 12.6 U/mg of protein. Analysis of subunit composition revealed a PDH (E1) consisting of the two subunits E1α (38 kDa) and E1β (56 kDa), a dihydrolipoamide acetyltransferase (E2) of 48 kDa, and a lipoamide dehydrogenase (E3) of 50 kDa. The E2 core of the complex is arranged to form a pentagonal dodecahedron, as shown by electron microscopic images, resembling the quaternary structures of PDH complexes from gram-positive bacteria and eukaryotes. The PDH complex-encoding genes were identified by hybridization experiments and sequence analysis in two separate gene regions in the genome of Z. mobilis. The genes pdhAα (1,065 bp) and pdhAβ (1,389 bp), encoding the E1α and E1β subunits of the E1 component, were located downstream of the gene encoding enolase. The pdhB (1,323 bp) and lpd (1,401 bp) genes, encoding the E2 and E3 components, were identified in an unrelated gene region together with a 450-bp open reading frame (ORF) of unknown function in the order pdhB-ORF2-lpd. Highest similarities of the gene products of the pdhAα, pdhAβ, and pdhB genes were found with the corresponding enzymes of Saccharomyces cerevisiae and other eukaryotes. Like the dihydrolipoamide acetyltransferases of S. cerevisiae and numerous other organisms, the product of the pdhB gene contains a single lipoyl domain. The E1β subunit PDH was found to contain an amino-terminal lipoyl domain, a property which is unique among PDHs. 相似文献
63.
64.
Eduard Solà Marta álvarez-Presas Cristina Frías-López D. Timothy J. Littlewood Julio Rozas Marta Riutort 《PloS one》2015,10(3)
Mitochondrial genomes (mitogenomes) are useful and relatively accessible sources of molecular data to explore and understand the evolutionary history and relationships of eukaryotic organisms across diverse taxonomic levels. The availability of complete mitogenomes from Platyhelminthes is limited; of the 40 or so published most are from parasitic flatworms (Neodermata). Here, we present the mitogenomes of two free-living flatworms (Tricladida): the complete genome of the freshwater species Crenobia alpina (Planariidae) and a nearly complete genome of the land planarian Obama sp. (Geoplanidae). Moreover, we have reanotated the published mitogenome of the species Dugesia japonica (Dugesiidae). This contribution almost doubles the total number of mtDNAs published for Tricladida, a species-rich group including model organisms and economically important invasive species. We took the opportunity to conduct comparative mitogenomic analyses between available free-living and selected parasitic flatworms in order to gain insights into the putative effect of life cycle on nucleotide composition through mutation and natural selection. Unexpectedly, we did not find any molecular hallmark of a selective relaxation in mitogenomes of parasitic flatworms; on the contrary, three out of the four studied free-living triclad mitogenomes exhibit higher A+T content and selective relaxation levels. Additionally, we provide new and valuable molecular data to develop markers for future phylogenetic studies on planariids and geoplanids. 相似文献
65.
Previous studies have shown that sensorimotor processing can often be described by Bayesian learning, in particular the integration of prior and feedback information depending on its degree of reliability. Here we test the hypothesis that the integration process itself can be tuned to the statistical structure of the environment. We exposed human participants to a reaching task in a three-dimensional virtual reality environment where we could displace the visual feedback of their hand position in a two dimensional plane. When introducing statistical structure between the two dimensions of the displacement, we found that over the course of several days participants adapted their feedback integration process in order to exploit this structure for performance improvement. In control experiments we found that this adaptation process critically depended on performance feedback and could not be induced by verbal instructions. Our results suggest that structural learning is an important meta-learning component of Bayesian sensorimotor integration. 相似文献
66.
67.
Male investment in testes and sperm duct gland in the polygamous nest breeding
two-spotted goby Gobiusculus flavescens (Fabricius) was
investigated in relation to time in reproductive season and individual physical
parameters. This small teleost fish is most likely the most abundant species
found along the rocky shores of the North East Atlantic. The two-spotted goby
has a single reproductive season, during which nest-caring males can raise
several clutches of offspring. According to the literature the males are on
average larger than the females. Here we report for the first time a population
showing a reversal of this trend, with males on average being smaller than
females, a difference likely caused by a large proportion of small males. Early
in the breeding season these small males have typical sneaker characters, with
relatively large testes and small seminal duct glands compared to the larger
dominant territorial males. The presence of these two alternative male
reproductive tactics is confirmed by histological studies, which shows the
presence of sperm in the sperm duct glands (SDG) of smaller males, but not in
the SDG of intermediate and larger males. To our knowledge, males with typical
sneaker characters have not been reported in earlier studied populations of
two-spotted goby. Interestingly we found that testes investment declined
significantly over the course of the breeding season, and that this reduction
was significantly more pronounced in small compared to the large males. Further,
a significant increase in seminal duct gland (SDG) mass was observed for the
smaller males over the breeding season. We propose that this indicates a
possible shift in mating tactic by smaller males from a parasitic to a
nest-holding tactic over the course of the breeding season. Thus, the observed
size dependent plasticity in investment in SDG over time suggests that the
reproductive tactic of G. flavescens is
conditional, and possibly influenced by mate availability and male—male
competition. 相似文献
68.
69.
Rupert Seidl Werner Rammer Panagiotis Bellos Eduard Hochbichler Manfred J. Lexer 《Trees - Structure and Function》2010,24(1):139-150
The allocation of carbohydrates from photosynthesis to various plant compartments is a key process in ecophysiology and consequently
an important element in process-based ecosystem modeling. In this study, we tested generalized empirical equations in a widely
applied partitioning concept based on compartment-specific biomass allometries. For an 88-year chronosequence of European
beech (Fagus sylvatica L.) in Austria, we used the individual-based hybrid forest model PICUS v1.4 to compare simulations employing foliage biomass
functions at different levels of generalization against runs with site-specific parameterization and observations. Sensitivities
of the individual tree model were generally in line with the original stand-level partitioning concept and ecological process
understanding. While stand-level leaf area increased with increasing allocation to foliage, net primary productivity showed
no significant response due to saturated radiation interception in the dense chronosequence stands. Strong sensitivities were
revealed at the individual tree level, where favoring allocation to the foliage compartment resulted in increasing asymmetry
of competition and height–diameter relationships. Applying a generalized parameterization based on data from the full range
of continental species distribution resulted in a significant overestimation of mean tree height and subsequently standing
volume stock at the chronosequence. At a lower hierarchical level of generality, however, simulations with a representative
regional parameterization performed satisfactorily compared to model runs using the site-specific allometry. In relation to
common accuracy demands, e.g., in forest management decision support, the study suggests the rejection of a generic parameterization
while corroborating the use of regional generalizations in ecosystem models. 相似文献
70.
Cashman JR MacDonald M Ghirmai S Okolotowicz KJ Sergienko E Brown B Garcia X Zhai D Dahl R Reed JC 《Bioorganic & medicinal chemistry letters》2010,20(22):6560-6564
High-throughput screening of 66,000 compounds using competitive binding of peptides comprising the BH3 domain to anti-apoptotic Bfl-1 led to the identification of 14 validated 'hits' as inhibitors of Bfl-1. N-Aryl maleimide 1 was among the validated 'hits'. A chemical library encompassing over 280 analogs of 1 was prepared following a two-step synthesis. Structure-activity studies for inhibition of Bfl-1 by analogs of N-aryl maleimide 1 revealed a preference for electron-withdrawing substituents in the N-aryl ring and hydrophilic amines appended to the maleimide core. Inhibitors of Bfl-1 are potential development candidates for anti-cancer therapeutics. 相似文献