Kidney plays a major role in ammonia homeostasis after portasystemic shunting in patients with cirrhosis

The kidney plays an important role in ammonia metabolism. In this study the hypothesis was tested that the kidney can acutely diminish ammonia release after portacaval shunting. Thirteen patients with cirrhosis (6 female/7 male, age 54.4 +/- 3.3 yr) were studied. Blood was sampled prior to and 1 h after transjugular intrahepatic stent-shunt (TIPSS) insertion from the portal vein, a hepatic vein, the right renal vein, and the femoral vein, and renal and liver plasma flow were measured. Prior to TIPSS, renal ammonia release was significantly higher than ammonia release from the splanchnic region, which was not significantly different from zero. TIPSS insertion did not change arterial ammonia concentration or ammonia release from the splanchnic region but reduced renal ammonia release into the circulation (P < 0.05) to values that were not different from zero. TIPSS resulted in a tendency toward increased venous-arterial ammonia concentration differences across leg muscle. Post-TIPSS ammonia efflux via portasystemic shunts was estimated to be seven times higher than renal efflux. Kidneys have the ability to acutely diminish systemic ammonia release after portacaval shunting. Diminished renal ammonia release and enhanced muscle ammonia uptake are important mechanisms by which the cirrhotic patient maintains ammonia homeostasis after portasystemic shunting.     

The effects of manganese on glutamate, dopamine and gamma-aminobutyric acid regulation

Exposure to high levels of manganese (Mn) results in a neurological disorder, termed manganism, which shares a similar phenotype to Parkinson's disease due to the involvement of the basal ganglia circuitry in both. The initial symptoms of manganism are likely due to the involvement of the globus pallidus, a region rich in gamma-aminobutyric acid (GABA) projections, while those of Parkinson's disease are related to the degeneration of the substantia nigra, a dopaminergic nucleus. Additionally, it is known that glutamate regulation is affected by increases in brain Mn levels. As Mn predominantly accumulates in the basal ganglia, it potentially could affect the regulation and interactions of all three neurotransmitters. This review will focus on the circuitry of these neurotransmitters within the basal ganglia and address potential sites for, as well as the temporal relationship, between Mn exposure and changes in the levels of these neurotransmitters. While most research has focused on perturbations in the dopaminergic system, there is evidence to support that early consequences of manganism also include disturbances in GABA regulation as well as glutamatergic-related excitotoxicity. Finally, we suggest that current research focus on the interdependence of these basal ganglial neurochemicals, with a greater emphasis on the GABAergic and glutamatergic systems.     

人乳腺癌多药耐药细胞系MCF-7/MDRa的建立及其生物学特性的初步研究

实验以MCF-7细胞株为亲本细胞,采用阿霉素(ADM)低浓度持续加量诱导法建立了多药耐药的人乳腺癌细胞系MCF-7/MDRa,并对其耐药谱、动力学周期分布、表型变化、药物的蓄积量等生物学特性进行了初步分析评价。结果表明,MCF-7/MDRa细胞较亲本细胞的ADM半数致死浓度(IC50)高500倍,撤药培养150天后耐药指数仍维持在200倍以上,并对多种化疗药物产生交叉耐药性;耐药细胞分化程度低于同步传代的MCF-7细胞,细胞倍增时间与亲本细胞接近,S期细胞显著增加,G1期细胞减少;随着撤药时间的延长,细胞的增殖速度加快;耐药细胞P-gP、LRP和GSTπ的表达水平较亲本细胞有显著增加,ER阳性表达丢失;在稳定生长的撤药培养6天的细胞中仍有ADM蓄积。建立的MCF-7/MDRa模型具有多药耐药细胞的基本生物学特性,可用于肿瘤多药耐药机制的研究。     

Wnt activation and alternative promoter repression of LEF1 in colon cancer

Alternative promoters within the LEF1 locus produce polypeptides of opposing biological activities. Promoter 1 produces full-length LEF-1 protein, which recruits beta-catenin to Wnt target genes. Promoter 2 produces a truncated form that cannot interact with beta-catenin and instead suppresses Wnt regulation of target genes. Here we show that promoter 1 is aberrantly activated in colon cancers because it is a direct target of the Wnt pathway. T-cell factor (TCF)-beta-catenin complexes bind to Wnt response elements in exon 1 and dynamically regulate chromatin acetylation and promoter 1 activity. Promoter 2 is delimited to the intron 2/exon 3 boundary and, like promoter 1, is also directly regulated by TCF-beta-catenin complexes. Promoter 2 is nevertheless silent in colon cancer because an upstream repressor selectively targets the basal promoter leading to destabilized TCF-beta-catenin binding. We conclude that the biological outcome of aberrant LEF1 activation in colon cancer is directed by differential promoter activation and repression.     

Nectar sugar composition and volumes of 47 species of Gentianales from a southern Ecuadorian montane forest

BACKGROUND AND AIMS: This study investigates 47 taxonomically related species (Gentianales), all native to a tropical montane forest in southern Ecuador, in terms of nectar chemistry and nectar volumes in relation to pollination biology. METHODS: Nectar volumes of covered (24-h production) and uncovered (standing crop) flowers were measured in the natural habitat. Sucrose, fructose and glucose were quantified in the nectar using high performance liquid chromatography. Flower visitors were observed. KEY RESULTS: Nectar sugar concentration did not differ significantly among the pollination syndromes. Regarding sugar composition, the only significant differences were found in chiropterophilous and myiophilous flowers, which had a significantly lower sugar ratio than sphingophilous flowers. A separation of chiropterophilous and myiophilous flowers from the other pollination syndromes is further substantiated by non-linear multidimensional scaling using the chord-normalized expected species shared index of dissimilarity based on nectar sugar compositions. The matrix test revealed no correlation of observed floral visitors to nectar concentrations; however, a weak significant correlation was found between floral visitors and nectar sugar compositions. The nectar volumes of covered and uncovered flowers are related to, and differ significantly among, pollination syndromes. Matrix tests revealed correlation between floral visitors and nectar volume of covered flowers and, to a lesser extent, of uncovered flowers. CONCLUSIONS: Sucrose is the predominant floral nectar sugar in the order Gentianales, suggesting that nectar sugar composition is a conservative characteristic. However, some degree of an adaptive convergence of floral nectar compositions to principal pollinator type within the constraints set by phylogenetic history is likely. The driving force to visitation appears to be the volume of nectar the visitor can expect to consume.     

Effects of selective estrogen receptor modulator raloxifene plus 17-beta estradiol in aorta and mammary gland of female experimental atherosclerosis rabbits and possible involvement of ERK signal transduction pathway

The present study investigated the effects of raloxifene, a second generation selective estrogen receptor modulator (SERM), plus 17-betaE2 on aortic atherosclerosis and mammary gland hyperplasia in ovariectomized, cholesterol-fed rabbits. Following 10 weeks of raloxifene, 17-betaE2, or raloxifene plus 17-betaE2 administration, serum total cholesterol, triglyceride, low density lipoprotein were significantly decreased in the drug groups compared to the placebo group. Consistent with serum lipid results, the total lesion area for each aorta of the drug groups decreased significantly as compared to the placebo group. HE staining of aorta paraffin section showed that in the drug groups the endothelial monolayer was almost continuous. While in mammary gland, HE staining of paraffin sections indicated the hyperplasia of epithelial cells (in 17-betaE2 group) was obviously inhibited in raloxifene plus 17-betaE2 group. In cultured vascular smooth muscle cell (VSMC), the results of MTT and [3H]TdR incorporation showed that the drug groups could inhibit AngII-induced proliferation of VSMC. Western blotting proved that raloxifene plus 17-betaE2 inhibited the expression of phosphorylated ERK protein, similar to 17-betaE2 but different from raloxifene. This effect was inhibited by PD98059 (inhibitor of MAPK) or ICI182780 (ER antagonist). In conclusion, this study suggests that SERM raloxifene plus 17-betaE2 improves the lipid metabolism and relieves the aorta changes of female experimental atherosclerosis rabbits, which are partly implemented by the inhibition of VSMC growth through ERK cascade. The hyperplasia of mammary gland epithelial cells could be significantly inhibited by raloxifene plus 17-betaE2.     

Very-long-chain secondary alcohols and alkanediols in cuticular waxes of Pisum sativum leaves

In cuticular waxes from leaves of Pisum sativum, 19 secondary alcohols, 10 primary/secondary alkanediols and three secondary/secondary alkanediols were identified by various chemical transformations with product assignment employing GC-MS. The homologous series of C29-C33 secondary alcohols (1.1 microg/cm2) was dominated by hentriacontanol isomers (94%). Only octacosanediols and trace amounts of hexacosanediols (< 1%) were detected in the primary/secondary alkanediol faction (0.7 microg/cm2). The secondary/secondary alkanediols (0.12 microg/cm2) contained a single homologue with chain length C31. All three compound classes showed characteristic isomer distributions with secondary functional groups predominantly located between C-14 and C-16. Based on the isomer compositions, the sequence of biosynthetic steps introducing the hydroxyl functions is discussed.     

Performance of wheat crops with different chromosome ploidy: root-sourced signals, drought tolerance, and yield performance

Pot-culture experiments were carried out to estimate the role of non-hydraulic root signals (nHRS) and the relation of these signals to drought tolerance and grain yield formation under drought stress in six wheat varieties. These were two modern hexaploid wheat (Triticum aestivum L., AABBDD) Plateau602 and Longchun8139-2, two diploid wheat (Triticum monococcum L., AB) MO1 and MO4, and two tetraploid wheat (Triticum dicoccum Schuebl L., AABB) DM22 and DM31. In the two diploid relatives, the nHRS was switched on and off at a soil water content (SWC) of approximately 53–45% field water capacity (FWC). In contrast, in the modern hexaploid varieties, Longchun8139-2 and Plateau602 the nHRS occurred between a SWC of about 71 and 35% FWC, a much wider soil moisture range. The two tetraploid relatives, DM22 and DM31, were generally intermediate. The nHRS threshold range in SWC also narrowed as all six varieties went through successive developmental stages from shooting to grain filling. The two hexaploid wheat varieties had the longest duration of survival after the water supply ceased, and the best yield stability under drought stress, similar to with tetraploid wheat varieties; the diploid wheat varieties were least robust. These two parameters were both significantly correlated with the nHRS soil moisture threshold range (r=0.9456** and 0.8608*, respectively). Based on these patterns, we propose a ‘triple Z’ model to describe the features of non-hydraulic stomatal sensitivity versus soil drought in wheat growth.     

Enhanced production of recombinant nattokinase in Bacillus subtilis by the elimination of limiting factors

By systematic investigation, glutamate and a mixture of metal ions were identified as factors limiting the production of nattokinase in Bacillus subtilis. Consequently, in medium supplemented with these materials, the recombinant strain secreted 4 times more nattokinase (260 mg l⁻¹) than when grown in the unsupplemented medium.