Differential distribution of endothelin receptor subtypes in placentae from normal and growth-restricted pregnancies

The endothelins (ETs) are potent vasoconstrictor peptides that bind to two distinct receptors, ETA and ETB. This study compares the localization of ETA and ETB receptors in placentae complicated by intrauterine growth retardation (IUGR) and abnormal umbilical Doppler waveform, gestationally matched controls, fetuses that were small for gestational age (SGA), and normal term placentae. Quantitative autoradiography was performed using ETA and ETB subtype-selective ligands. Both ETA and ETB receptors were expressed in the human placenta. Gestational and fetal size effects on the receptor density within stem villi were found, but no effect of abnormal placental blood flow could be demonstrated. A distinct spatial distribution of receptor subtypes within the placenta was observed. Smooth muscle cells expressed both receptors with ETA expression predominant in the proximal regions of the villous tree and ETB abundant in the periphery and decidua. Both receptors were also expressed at lower density on paravascular stromal cells in stem villi. Although these data do not demonstrate aberrant localization of ET receptors in IUGR and SGA placentae, the spatially distinct distribution of ET receptors in the human placenta suggests that ETs play a role in modulation of placental blood flow.     

Model structure of decorin and implications for collagen fibrillogenesis

The three-dimensional structure of human decorin, a secreted proteoglycan involved in the regulation of collagen fibrillogenesis and cellular growth, has been modeled based on the crystal structure of the porcine ribonuclease inhibitor. Both proteins contain leucine-rich repeats and share 18% identical residues. This model structure of decorin has an arch shape with the single glycosaminoglycan chain and the three N-linked oligosaccharides located on the same side of the molecule. Decorin was modeled as binding to a polar sequence of collagen type I found in the d band. The inner concave surface is the appropriate size and shape to accommodate only one collagen triple helix of approximately 3 nm in length. The binding of one collagen triple helix to decorin is proposed to play a major role in the formation of the staggered arrangement of collagen molecules within the microfibrils by preventing lateral fusion of collagen molecules.     

Virus and host-specific adaptations in the BL1 and BR1 genes of bipartite geminiviruses

The host range of individual geminiviruses may be quite narrow, and closely related viruses can exhibit distinct host adaptations. Two such bipartite geminiviruses are bean golden mosaic virus (GBMV) and tomato golden mosaic virus (TGMV). In both, the BL1 and BR1 genes are required for the spread of virus infection in plants. We have investigated the contributions of BL1 and BR1 to host-specific phenotypes of BGMV and TGMV by constructing hybrid viruses in which these coding regions were exchanged. Hybrids were assayed on bean, a good host for BGMV, and Nicotiana benthamiana, a good host for TGMV. A BGMV hybrid having TGMV BL1 and BR1 efficiently infected beans, but elicited attenuated symptoms. In N. benthamiana, this hybrid had slightly increased virulence and DNA accumulation relative to wild-type BGMV. A TGMV hybrid having BGMV BL1 and BR1 was virulent in N. benthamiana, but elicited attenuated symptoms. However, this hybrid exhibited no gain of function in beans relative to wild-type TGMV. Hybrid viruses with TGMV BL1 and BGMV BR1 had severely defective phenotypes in either viral or host background. Although exchanging BL1 and BR1 between BGMV and TGMV did not change host range, some host adaptation of these genes is suggested. However, virus-specific compatibility between BL1 and BR1 is of more importance for viability. Thus, these gene products may act in concert to potentiate virus movement.     

Mutagenesis of human adenosine deaminase to active forms that partially resist inhibition by pentostatin

Human adenosine deaminase (ADA) cDNA was randomly mutagenized in vitro and bacterial transformants were selected for resistance to the potent enzyme inhibitor, pentostatin (dCF). Cells transformed with mutant plasmids dCF-R2 and dCF-R6 were able to grow in the presence of 10(-6) M dCF, whereas 10(-11) M dCF blocked growth of cells complemented with wild-type ADA. DNA sequence analysis revealed double G/A conversions mutating Lys11 and Gln255 in dCF-R2, and Gly 31 and Glu 99 in dCF-R6, to different amino acids. Located far from the enzyme active site, these substitutions did not greatly affect the Km or Ki of the enzyme but were predicted to destabilize interactions within the enzyme structure. Mutants such as these may be useful to analysis of the stereology of inhibitor binding to ADA and toxicity of dCF.     

2006年5月份笔记本电脑性价比排名

NO.1索尼V G N-SZ12C●处理器:IntelCore Solo T1300处理器(1.3GHz主频,2MB二级缓存)●显卡:IntelGMA950集成显卡+NvidiaGeForce Go7400独立显卡●屏幕:13.3英寸宽屏●内存:512M DDR2533●硬盘:80G●光驱:COMBO价格:14988元索尼SZ最吸引人的卖点要数双显卡的设计,在娱乐的时候,使用独立显卡保证性能的强劲,而在移动使用的时候,切换到集成显卡就能增加整机的续航时间,最长可达7小时。除此之外,采用13.3英寸宽屏的SZ具有十分出色的便携性,整机的性能也足够强劲。SZ的出现,无疑展示了索尼的高超制造工艺。NO.2宏鸉T ravelM a…     

Ambulatory esophageal manometry/pH-metry discriminates between patients with different esophageal symptoms

The use of glutathione glycoside (GSH-glyc), a compound newly synthesized in our laboratory, was highly effective in raising cellular GSH levels both in vitro and in vivo. Based on mass spectrometry and 1H NMR data, the structure of GSH-glyc was determined to be that of an S-glycoside. Rapid GSH uptake was observed by confocal microscopy in both A549 cells and mouse astrocytes following incubation with GSH-glyc. Intraperitoneal (i.p.) and per oral administration of GSH-glyc in C57BL/6J mice raised GSH concentrations in brain and liver to significantly higher levels than normal. Methyl mercury (MeHg) poisoning of mice with multiple doses of methylmercuric chloride (MMC) induced severe toxic effects associated with marked depletion of brain and liver GSH progressing to death in all animals, whereas the animals primed with GSH-glyc and given MMC and GSH-glyc concurrently were devoid of toxic signs. We suggest, on the basis of D-[3H]glucose and [2- 3H]deoxyglucose uptake studies, that the transport of GSH-glyc across the blood-brain barrier may occur through one of the glucose transport pathways. Although the precise mechanism by which GSH-glyc protects against MeHg poisoning is not clear, it is probable that any one of a number of factors, including conjugation of MeHg, scavenging of free radicals, restoration of reactive thiol groups, and enhancement of MeHg efflux, may have been instrumental. GSH-glyc is a nontoxic compound that can be used to transport GSH into cells, including those of brain and liver, and may prove to be useful for prophylaxis and therapy of tissue injury induced by various neurotoxic compounds, particularly when the capacity to synthesize or regenerate GSH has been compromised.