地塞美松中间体的C1,4脱氢和11α-羟基化

地塞美松 (Ｄｅｘａｍｅｔｈａｓｏｎｅ)为高效肾上腺皮质激素药物 ,临床上广泛使用。开拓用梯可吉宁 (Ｔｉｇｏｇｅｎｉｎ)为起始原料生产从化学结构和合成技术上讲较为合理 ,而且适合于资源综合利用[1] 。在合成过程中 ,除了Ａ环需引入Ｃ1,2 和Ｃ4 ,5两个双键 (含Ｃ-3 羟基氧化 )外 ,还需用微生物法在Ｃ-11位引入羟基。国外常采用化学法脱氢 ,然后再用霉菌 11α 羟基化[2 ,3 ] 。本文报道用两类微生物菌种 ,节杆菌 (Ａｒｔｈｒｏｂａｃｔｅｒｓｐ .)ＡＸ86和绿僵菌 (Ｍｅｔａｒｈｉｚｉｕｍｓｐ .)Ｍ 88,混合转化一步完成脱氢和羟基化反应…     

甾体1，4-脱氢和11α-羟基化反应的两种不同微生物转化

Two kinds of micro-organism, Arthrobacter sp. AX86(1,4-dehdrogenator)and Absidia sp. A28(11α-hydroxylator) were used in this experiment. Two different fermentation techniques were performed to accomplish the multiple conversional reactions for producing 16β-methyl-11α, 17α, 21-trihydroxy-1,4-pregnadiene-3,20-dione (Ⅲ) from 16β-methyl-3β, 17α,21-trihydroxy-5α-pregnane-20-one-21-acetate(1) 1)To produce product(Ⅲ)by means of a two-step fermentation method which were independently performed first by Arthrobacter and next by Abslaia, and 2)the product was obtained by a sequential fermentation system of aforesaid two micro-organisms in a single fermentor without isolation of the intermediates from the mixture. Our results showed that in both fermentation systems high yield of product was obtained. However, according to the technical simplicity, shorter duration of fermentation cycle and efficient yield of product, the second method is better than the first one.     

Modulation of P-glycoprotein-mediated drug transport by alterations in lipid fluidity of rat liver canalicular membrane vesicles.

P-glycoprotein (P-gp) is believed to function as an ATP-dependent efflux pump for natural product anti-cancer drugs in multidrug-resistant (MDR) tumor cells and in certain normal tissues. P-gp has been localized to the apical plasma membrane of the bile canaliculus where it has been shown to transport [3H]daunomycin. In this study, we investigated whether alterations in membrane lipid fluidity of canalicular membrane vesicles (CMV) could modulate the P-gp-mediated accumulation of [3H]daunomycin and [3H]vinblastine. Accumulation of both cytotoxic agents was stimulated by ATP, exhibited temperature dependence and osmotic sensitivity, and followed Michaelis-Menten kinetics. Alterations in CMV lipid fluidity were induced by the known fluidizers, 2-(2-methoxyethoxy)ethyl 8-(cis-2-n-octylcyclopropyl)octanoate (A2C) and benzyl alcohol, and were assessed by fluorescence polarization techniques using the fluorescent probe, 1,6-diphenyl-1,3,5-hexatriene (DPH). Both A2C (2.5-5.0 microM) and benzyl alcohol (10-20 mM) produced a dose-dependent increase in CMV lipid fluidity. Moreover, both fluidizers, at the above doses, significantly inhibited (p < 0.05) the ATP-dependent accumulation of [3H]daunomycin. [3H]Vinblastine accumulation was also inhibited by A2C (p < 0.05). Lower doses of A2C (0.6 microM) and benzyl alcohol (1 mM) failed to influence either lipid fluidity or P-gp-mediated drug accumulation. Kinetic analysis revealed that A2C (5.0 microM) noncompetitively inhibited [3H]daunomycin accumulation and uncompetitively inhibited [3H]vinblastine accumulation with apparent Ki values of approximately 1.5 and approximately 1.2 microM, respectively. Verapamil competitively inhibited P-gp-mediated accumulation of [3H]daunomycin but failed to alter the fluidity of CMV. Taken together, the present results demonstrate that while increases in membrane fluidity of CMV are not necessarily required to inhibit P-gp-mediated drug accumulation, they can inhibit these processes, at least in CMV. Alterations in the physical state of CMV, therefore, appear to be at least one important modulator of P-gp function.     

Influence of habitat characteristics on small mammals in a Mexican high-altitude grassland

Small mammals in a high-altitude grassland area close to Mexico City were studied. Populations of 10 species were censused using live traps in 48 sample quadrats. Within each quadrat, vegetation characterization, including complete floristic listings, cover values for species and layers and values of habitat modification, were assessed. Habitats were described according to plant communities identified using ordination and classification methods. Nine different plant communities were obtained. Densities and abundance of all small mammal species were calculated for each of the habitats classified. Peromyscus alsloni was the most abundant species in all habitats, reaching maximum densities of 55 ha⁻¹ in pine forest with dense ground and herb layer. Peromyscus melanotis also occurred in all habitats but at lower densities (maximum 29 ha⁻¹). Reithrodontomys megalotis was found in all habitats except in tall dense grassland. Densities for this species were generally low (1-9 ha⁻¹) but reached 19 ha⁻¹ in short dense grassland. All other species were largely absent from 4–8 habitats and showed very low densities (0.75–4 ha⁻¹). The densities of the more abundant species were largely correlated with more open habitats and higher indices of habitat modification. Lower altitude grassland habitats have a greater abundance of small mammals and a higher species richness than the medium and higher altitude, physiognomically more complex habitats. Species richness was highest in tall pine-alder forest with a species-rich, dense herb layer and lowest in pine forest with dense ground and herb layers. Species richness was positively correlated with overall small mammal density.     

Conditional QTL mapping of protein content in wheat with respect to grain yield and its components

Grain protein content in wheat (Triticum aestivum L.) is generally considered a highly heritable character that is negatively correlated with grain yield and yield-related traits. Quantitative trait loci (QTL) for protein content was mapped using data on protein content and protein content conditioned on the putatively interrelated traits to evaluate possible genetic interrelationships between protein content and yield, as well as yield-related traits. Phenotypic data were evaluated in a recombinant inbred line population with 302 lines derived from a cross between the Chinese cultivar Weimai 8 and Luohan 2. Inclusive composite interval mapping using IciMapping 3.0 was employed for mapping unconditional and conditional QTL with additives. A strong genetic relationship was found between protein content and grain yield, and yield-related traits. Unconditional QTL mapping analysis detected seven additive QTL for protein content, with additive effects ranging in absolute size from 0.1898% to 0.3407% protein content, jointly accounting for 43.45% of the trait variance. Conditional QTL mapping analysis indicated two QTL independent from yield, which can be used in marker-assisted selection for increasing yield without affecting grain protein content. Three additional QTL with minor effects were identified in the conditional mapping. Of the three QTLs, two were identified when protein content was conditioned on yield, which had pleiotropic effects on those two traits. Conditional QTL mapping can be used to dissect the genetic interrelationship between two traits at the individual QTL level for closely correlated traits. Further, conditional QTL mapping can reveal additional QTL with minor effects that are undetectable in unconditional mapping.     

Impacts of hunting on mammals in African tropical moist forests: a review and synthesis

• 1 Available information on the consumption of wild meat in West and Central Africa is reviewed. We show that mammals are the prime source of bushmeat, and that ungulates and rodents make up the highest proportion of biomass extracted.
• 2 We present data on current knowledge of extraction patterns of wild mammals in West and Central Africa, and evidence that at current off‐take levels, within the range states, mammals as bushmeat are being depleted on an unprecedented scale. Extraction rates are orders of magnitude higher there than in comparable ecosystems like the Amazon, and much less likely to be sustainable.
• 3 However, basic knowledge of the biology of harvestable tropical moist forest mammals, and the consequences of hunting on mammalian communities, which permits accurate estimation of maximal production rate (the excess of growth over replacement rate), is largely unavailable, and this hinders estimation of hunting quotas and sustainability. Comparisons are made with the existing information available on Amazon basin mammals and hunting patterns reported there.

     

A comparison of univariate and multivariate gene selection techniques for classification of cancer datasets

Background  

Gene selection is an important step when building predictors of disease state based on gene expression data. Gene selection generally improves performance and identifies a relevant subset of genes. Many univariate and multivariate gene selection approaches have been proposed. Frequently the claim is made that genes are co-regulated (due to pathway dependencies) and that multivariate approaches are therefore per definition more desirable than univariate selection approaches. Based on the published performances of all these approaches a fair comparison of the available results can not be made. This mainly stems from two factors. First, the results are often biased, since the validation set is in one way or another involved in training the predictor, resulting in optimistically biased performance estimates. Second, the published results are often based on a small number of relatively simple datasets. Consequently no generally applicable conclusions can be drawn.