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991.
Knowledge of the rapidly developing hierarchy of controls affecting vascular development in placenta is required to understand how the growth factors and their receptor-mediated signals actually produce vessels. At the cell biological level, these events clearly require stable interactions between the cells, and cells with the surrounding ECM. The objective of the study was to understand the role of integrins and ECM on the expression and secretion of angiogenin in placentas and from trophoblasts in culture. Functionally active term placental explant culture and trophoblast cultures were used to demonstrate the differential secretion profile of angiogenin and real-time quantitative RT-PCR to demonstrate the mRNA expression in the presence or absence of ECM proteins. In this study, a significant increase in expression and secretion of angiogenin occurred in the presence of vitronectin (VN) and fibronectin (FN). Using antibody-blocking experiments it was also demonstrated that the angiogenin secretion is mediated by placental integrins, alpha(V)beta3 and alpha5beta1. In addition, exposure to hypoxic conditions resulted in diminished angiogenin secretion in the presence of both ECMs suggesting that angiogenin expression in the presence of ECM is modulated by local O2 concentration. In conclusion, this study provides evidence for the regulatory role of ECM and integrins on the mRNA expression and secretion of angiogenin in human placenta. ECMs may have a pivotal role in enhancing secretion of this peptide necessary for placental angiogenesis and provides the impetus as additional targets for the control of angiogenesis in pathological pregnancy.  相似文献   
992.
A population-based LD map of the human chromosome 6p   总被引:1,自引:0,他引:1  
Yu HX  Chia JM  Bourque G  Wong MV  Chan SH  Ren EC 《Immunogenetics》2005,57(8):559-565
The recent publication of the complete sequence of human chromosome 6 provides a platform from which to investigate genomic sequence variation. We report here a detailed linkage disequilibrium (LD) pattern map across the entire human chromosome 6p by using a set of 1152 single nucleotide polymorphisms (SNPs) in a population of 198 Singaporean Chinese, with 326 SNPs focused in the major histocompatibility complex (MHC) region. Our analysis shows some unexpectedly high segments of strong LD in a 10-Mb region that includes the extremely polymorphic and gene-rich MHC loci and many non-MHC genes. These include the telomeric peri-MHC region that harbors olfactory receptors, histones and zinc finger clusters, and the centromeric peri-MHC region that contains several unknown open reading frames. The data also help refine a human–mouse synteny break in the region between 28.6 and 29.4 Mb. The population-based LD map presented here will provide an essential resource for understanding the genomic sequence variation of chromosome 6p and LD mapping of disease genes of complex genetic traits. Electronic supplementary material Electronic supplementary material is available for this article at and accessible for authorised users. H. Yu and J.-M. Chia should be regarded as joint first authors.  相似文献   
993.
994.
We describe here a new enzyme-coupled assay for the quantitation of d-xylose using readily available enzymes that allows kinetic evaluation of hemicellulolytic enzymes using natural xylooligosaccharide substrates. Hydrogen peroxide is generated as an intermediary analyte, which allows flexibility in the choice of the chromophore or fluorophore used as the final reporter. Thus, we present d-xylose quantitation results for solution-phase assays performed with both the fluorescent reporter resorufin, generated from N-acetyl-3,7-dihydroxyphenoxazine (Amplex Red), and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate) (ABTS), whose corresponding radical cation has an absorbance maximum at approximately 400 nm. We also describe a useful solid-phase variation of the assay performed with the peroxidase substrate 3,3'-diaminobenzidine tetrahydrochloride, which produces an insoluble brown precipitate. In addition, kinetic parameters for hydrolysis of the natural substrates xylobiose and xylotriose were obtained using this assay for a glycosyl hydrolase family 39 beta-xylosidase from Thermoanaerobacterium sp. strain JW/SL YS485 (Swiss-Prot accession no. O30360). At higher xylobiose substrate concentrations the enzyme showed an increase in the rate indicative of transglycosylation, while for xylotriose marked substrate inhibition was observed. At lower xylobiose concentrations k(cat) was 2.7 +/- 0.4 s(-1), K(m) was 3.3 +/- 0.7 mM, and k(cat)/K(m) was 0.82 +/- 0.21 mM(-1) . s(-1). Nonlinear curve fitting to a substrate inhibition model showed that for xylotriose K(i) was 1.7 +/- 0.1 mM, k(cat) was 2.0 +/- 0.1 s(-1), K(m) was 0.144 +/- 0.011 mM, and k(cat)/K(m) was 14 +/- 1.3 mM(-1) . s(-1).  相似文献   
995.
Wong HY  Chu TS  Chan YW  Fok TF  Fung LW  Fung KP  Ho YY 《Life sciences》2005,76(16):1859-1872
Glucose is the principal fuel for brain metabolism and its movement across the blood-brain barrier depends on Glut1. Impaired glucose transport to the brain may have deleterious consequences. For example, Glut1 deficiency syndrome (Glut1DS) is the result of heterozygous loss of function Glut1 mutation leading to energy failure of the brain and subsequently, epileptic encephalopathy. To preserve the integrity of the energy supply to the brain in patients with compromised glucose transport function, consumption of compounds with glucose transport inhibiting properties should be avoided. Phenytoin is a widely used anticonvulsant that affects carbohydrate metabolism. In this study, the hypothesis that phenytoin and its metabolite 5-(4-hydroxyphenyl)-5-phenylhydantoin (HPPH) affect cellular glucose transport was tested. With a focus on Glut1, the effects of phenytoin and HPPH on cellular glucose transport were studied. Glucose uptake assay measuring the zero-trans influx of radioactive-labeled glucose analogues showed that phenytoin and HPPH did not exert immediate effects on erythrocyte Glut1 activity or glucose transport in Hs68 control fibroblasts, Glut1DS primary fibroblasts isolated from two patients, or in rat primary astrocytes. Prolonged exposure to the two compounds could stimulate glucose transport by up to 30-60% over the control level (p <0.05) in Hs68 and Glut1DS fibroblasts as well as in rat astrocytes. The stimulation of glucose transport by HPPH was dose-dependent and accompanied by an up-regulation of GLUT1 mRNA expression (p <0.05). In conclusion, phenytoin and HPPH do not compromise cellular glucose transport. Prolonged exposure to these compounds can modify carbohydrate homeostasis by up-regulating glucose transport in both normal and Glut1DS conditions in vitro.  相似文献   
996.
In this report, the antiviral activity of 80R immunoglobulin G1 (IgG1), a human monoclonal antibody against severe acute respiratory syndrome coronavirus (SARS-CoV) spike (S) protein that acts as a viral entry inhibitor in vitro, was investigated in vivo in a mouse model. When 80R IgG1 was given prophylactically to mice at doses therapeutically achievable in humans, viral replication was reduced by more than 4 orders of magnitude to below assay limits. The essential core region of S protein required for 80R binding was identified as a conformationally sensitive fragment (residues 324 to 503) that overlaps the receptor ACE2-binding domain. Amino acids critical for 80R binding were identified. In addition, the effects of various 80R-binding domain amino acid substitutions which occur in SARS-like-CoV from civet cats, and which evolved during the 2002/2003 outbreak and in a 2003/2004 Guangdong index patient, were analyzed. The results demonstrated that the vast majority of SARS-CoVs are sensitive to 80R. We propose that by establishing the susceptibility and resistance profiles of newly emerging SARS-CoVs through early S1 genotyping of the core 180-amino-acid neutralizing epitope of 80R, an effective immunoprophylaxis strategy with 80R should be possible in an outbreak setting. Our study also cautions that for any prophylaxis strategy based on neutralizing antibody responses, whether by passive or active immunization, a genotyping monitor will be necessary for effective use.  相似文献   
997.
Assessing the generality of global leaf trait relationships   总被引:14,自引:0,他引:14  
Global-scale quantification of relationships between plant traits gives insight into the evolution of the world's vegetation, and is crucial for parameterizing vegetation-climate models. A database was compiled, comprising data for hundreds to thousands of species for the core 'leaf economics' traits leaf lifespan, leaf mass per area, photosynthetic capacity, dark respiration, and leaf nitrogen and phosphorus concentrations, as well as leaf potassium, photosynthetic N-use efficiency (PNUE), and leaf N : P ratio. While mean trait values differed between plant functional types, the range found within groups was often larger than differences among them. Future vegetation-climate models could incorporate this knowledge. The core leaf traits were intercorrelated, both globally and within plant functional types, forming a 'leaf economics spectrum'. While these relationships are very general, they are not universal, as significant heterogeneity exists between relationships fitted to individual sites. Much, but not all, heterogeneity can be explained by variation in sample size alone. PNUE can also be considered as part of this trait spectrum, whereas leaf K and N : P ratios are only loosely related.  相似文献   
998.
Two novel hybrid molecules 3-O-sulfo-alpha/beta-galactosylceramide 3 and 4, which are derived from an immunostimulatory agent alpha-GalCer 1 and self-glycolipid ligand sulfatide 2, were designed and synthesized. Compound 3 was shown to efficiently stimulate human NKT cells to secret IL-4 and IFN-gamma, with activities similar to 1, suggesting that modification of the 3'-OH position of the galactose moiety with sulfate has no significant effect on NKT cell stimulation. As a comparison, the beta-isomer 4 has no affinity to NKT cells, which demonstrates that the alpha-glycosidic bond of galactosylceramide is crucial to the NKT cells activation.  相似文献   
999.
We report here the use of TEV protease cleavable fusion proteins to produce glycosylated bioactive peptides and proteins. Bacterial expression was utilized to produce two fusion proteins, GPRT-C37-H6 and His-tagged interleukin-2 (amino acids 6-133), which when cleaved by the tobacco etch virus NIa protease (TEV protease) to generate HIV entry inhibitor peptide C37-H6 and a truncated version of the cytokine interleukin-2, both containing N-terminal cysteines. The N-terminal cysteine containing C37-H6 and truncated interleukin-2 were then joined to a synthetic glycopeptide thioester utilizing native chemical ligation under nondenaturing and denaturing conditions, respectively. The ligations of the glycopeptide to the C37-H6 peptide and the truncated interleukin-2 protein both proceeded in high yield, though the size, and physical properties of the two polypeptides differ greatly.  相似文献   
1000.
Little is known about ciliogenesis as it proceeds through the entire airway tree, from the trachea to the terminal bronchioles, especially during the postnatal period. The purpose of this study was to define the spatial and temporal (prenatal and postnatal) pattern of normal cilia development in the mouse. Three airway generations representing the entire airway tree were examined: trachea, lobar bronchi, and terminal bronchiole. Ciliated cells in lung lobe whole mounts were labeled with a fluorescent dye for confocal microscopy, and ciliated cell surface density was measured for each airway generation and age. The same samples were examined by scanning electron microscopy to verify the appearance of ciliated cells among the differentiating epithelium of the airways. Ciliated cells were first detected in the trachea and lobar bronchi at 16 days gestational age (DGA) and in the terminal bronchioles at 18 DGA. Ciliated cell surface density increased with prenatal and postnatal age at all airway levels. However, the ciliated cell surface density of the trachea and lobar bronchi was always greater compared with the terminal bronchiole. In conclusion, the study revealed that in developing tracheobronchial airways of the mouse: 1) Ciliogenesis differs temporally and spatially by airway generation; 2) Ciliated cell surface density increases with age in all airway generations, but density decreases in a proximal to distal direction; and 3) A significant portion of ciliogenesis continues after birth. This study provides a healthy basis for investigations of neonatal pulmonary disease or pollutant toxicity affecting cilia and its functions.  相似文献   
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