Search results for "techniques"
showing 10 items of 4426 documents
A web application for the unspecific detection of differentially expressed DNA regions in strand-specific expression data
2015
Abstract Genomic technologies allow laboratories to produce large-scale data sets, either through the use of next-generation sequencing or microarray platforms. To explore these data sets and obtain maximum value from the data, researchers view their results alongside all the known features of a given reference genome. To study transcriptional changes that occur under a given condition, researchers search for regions of the genome that are differentially expressed between different experimental conditions. In order to identify these regions several algorithms have been developed over the years, along with some bioinformatic platforms that enable their use. However, currently available appli…
A hypothetical model of the influence of inorganic phosphate on the kinetics of pyruvate kinase
2000
This paper presents a simple solution to the problem of approximating the calculated curve of reaction progress to the measured curve which is usually disturbed by initial oscillation of auxiliary lactate dehydrogenase (LDH) reaction. The experiments leading to the determination of the apparent Km for phosphoenolpyruvate (PEP) and Vm were performed. For precise estimation of kinetic parameters (Km and Vm) of the M1 isozyme of pyruvate kinase (PK), measured by coupling it to LDH reaction, the sequence of Michaelis‐Menten for pyruvate kinase and second-order kinetics for lactate dehydrogenase reaction as well as a non-zero initial concentration of lactate was assumed. The functions of apparen…
The Gaia-ESO survey: Discovery of a spatially extended low-mass population in the Vela OB2 association
2015
The nearby (distance~350-400 pc), rich Vela OB2 association, includes $\gamma^2$ Velorum, one of the most massive binaries in the solar neighbourhood and an excellent laboratory for investigating the formation and early evolution of young clusters. Recent Gaia-ESO survey observations have led to the discovery of two kinematically distinct populations in the young (10-15 Myr) cluster immediately surrounding $\gamma^2$ Velorum. Here we analyse the results of Gaia-ESO survey observations of NGC 2547, a 35 Myr cluster located two degrees south of $\gamma^2$ Velorum. The radial velocity distribution of lithium-rich pre-main sequence stars shows a secondary population that is kinematically distin…
Semisynthesis of antitumoral acetogenins: SAR of functionalized alkyl-chain bis-tetrahydrofuranic acetogenins, specific inhibitors of mitochondrial c…
2000
The acetogenins of Annonaceae are known by their potent cytotoxic activity. In fact, they are promising candidates as a new future generation of antitumoral drugs to fight against the current chemiotherapic resistant tumors. The main target enzyme of these compounds is complex I (NADH:ubiquinone oxidoreductase) of the mitochondrial respiratory chain, a key enzymatic complex of energy metabolism. In an attempt to characterize the relevant structural factor of the acetogenins that determines the inhibitory potency against this enzyme, we have prepared a series of bis-tetrahydrofuranic acetogenins with different functional groups along the alkyl chain. They comprise several oxo, hydroxylimino,…
Synthesis and pharmacology of 6-substituted benztropines: discovery of novel dopamine uptake inhibitors possessing low binding affinity to the dopami…
2005
A series of 6alpha- and 6beta-substituted benztropines were synthesized. A marked enantioselectivity was observed for the 6beta-methoxylated benztropines, the (1R)-isomers being more potent than the corresponding (1S) compounds. The racemic 6alpha-methoxy-3-(4',4' '-difluorodiphenylmethoxy)tropane (5 g) was the most potent compound. It has been found that modifications at the 6-position of benztropine might reduce the DAT binding affinity, maintaining otherwise a significant dopamine uptake inhibitory activity. A reinvestigation of the absolute configuration of 6beta-methoxytropinone proved the 6R configuration for the (+)-enantiomer.
Stereoselective metabolism of dibenz(a,h)anthracene to trans-dihydrodiols and their activation to bacterial mutagens.
1990
Dibenz(a,h)anthracene (DBA), a carcinogenic, polycyclic aromatic hydrocarbon ubiquitous in the environment, is metabolized by the hepatic microsomal fraction of immature Sprague-Dawley rats pretreated with Aroclor 1254 to 27 ethyl acetate-extractable metabolites. More than half of these metabolites (51%) consisted of trans-1,2-; -3,4-; and -5,6-dihydrodiols including their identified secondary metabolites. The three trans-dihydrodiols (4.9, 15.8, and 0.6% of total metabolic conversion) were highly enriched in their R,R enantiomers (85, 71, and 98%) as determined by high performance liquid chromatography on suitable chiral stationary phases. This is explained on the basis of the stereoselect…
Tetrandrine and Isotetrandrine, Two Bisbenzyltetrahydroisoquinoline Alkaloids from Menispermaceae, with Rat Uterine Smooth Muscle Relaxant Activity
1992
Abstract The effects of two bisbenzyltetrahydroisoquinoline alkaloids, 1S, 1′S tetrandrine and its isomer 1R, 1′S isotetrandrine, were investigated in rat isolated uterus in order to identify the mechanism of relaxant action and to study the influence of the absolute configuration on the activity of these alkaloids. Both inhibited the uterine contraction induced by high K+, acetylcholine and oxytocin. In Ca2+-free medium, isotetrandrine relaxed the sustained contraction induced by oxytocin but tetrandrine did not. The relaxant effects of the alkaloids may be due to blockade of calcium influx through specific channels. Tetrandrine and isotetrandrine modify the calcium channel in a nonreversi…
α-Adrenoceptor Interaction of Tetrandrine and Isotetrandrine in the Rat: Functional and Binding Assays
1998
Abstract The action of 1S,1′S-tetrandrine, a bisbenzyltetrahydroisoquinoline alkaloid, on α1-adrenoceptors has been compared with that of its isomer 1R,1′S-isotetrandrine. The work includes binding assays to analyse the affinity of these products for the [3H]prazosin binding site of rat cerebral cortical membranes and functional studies on rat isolated aorta to examine the effects of both alkaloids on intracellular calcium processes related or not to α-adrenoceptor activation. A radioligand receptor-binding study showed that both compounds interacted with the α1-adrenoceptors displacing [3H]prazosin from the specific binding site. The Ki values (inhibition constants) were 0.69±0.12 and 1.6±…
Synthesis, benzodiazepine receptor binding and molecular modelling of isochromeno[4,3-c]pyrazol-5(1H)-one derivatives
2012
Abstract A series of isochromeno[4,3-c]pyrazole-5(1H)-one derivatives 7b–h were prepared and tested at 10 μM for their ability to displace specific [3H]flunitrazepam from bovine brain membranes. The substitution pattern of the above derivatives was shown to influence the receptor affinity. The most active compound of the series was 7e, showing a 54% inhibition of [3H]flunitrazepam binding. Compounds 7a–d,i were compared with the known isomers chromeno[4,3-c]pyrazole-4(1H)-ones 14a–d,i, showing that the isochromene/chromene isomerism influences the activity.
Natural substances (acetogenins) from the family Annonaceae are powerful inhibitors of mitochondrial NADH dehydrogenase (Complex I).
1994
Natural products from the plants of the family Annonaceae, collectively called Annonaceous acetogenins, are very potent inhibitors of the NADH-ubiquinone reductase (Complex I) activity of mammalian mitochondria. The properties of five of such acetogenins are compared with those of rotenone and piericidin, classical potent inhibitors of Complex I. Rolliniastatin-1 and rolliniastatin-2 are more powerful than piericidin in terms of both their inhibitory constant and the protein-dependence of their titre in bovine submitochondrial particles. These acetogenins could be considered therefore the most potent inhibitors of mammalian Complex I. Squamocin and otivarin also have an inhibitory constant …