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1.
Processing of viral envelope glycoprotein by the endomannosidase pathway: evaluation of host cell specificity 总被引:4,自引:2,他引:2
Endo-alpha-D-mannosidase is an enzyme involved in N-linked oligosaccharide
processing which through its capacity to cleave the internal linkage
between the glucose-substituted mannose and the remainder of the
polymannose carbohydrate unit can provide an alternate pathway for
achieving deglucosylation and thereby make possible the continued formation
of complex oligosaccharides during a glucosidase blockade. In view of the
important role which has been attributed to glucose on nascent
glycoproteins as a regulator of a number of biological events, we chose to
further define the in vivo action of endomannosidase by focusing on the
well characterized VSV envelope glycoprotein (G protein) which can be
formed by the large array of cell lines susceptible to infection by this
pathogen. Through an assessment of the extent to which the G protein was
converted to an endo-beta-N- acetylglucosaminidase (endo H)-resistant form
during a castanospermine imposed glucosidase blockade, we found that
utilization of the endomannosidase-mediated deglucosylation route was
clearly host cell specific, ranging from greater than 90% in HepG2 and PtK1
cells to complete absence in CHO, MDCK, and MDBK cells, with intermediate
values in BHK, BW5147.3, LLC-PK1, BRL, and NRK cell lines. In some of the
latter group the electrophoretic pattern after endo H treatment suggested
that only one of the two N-linked oligosaccharides of the G protein was
processed by endomannosidase. In the presence of the specific
endomannosidase inhibitor, Glcalpha1-->3(1- deoxy)mannojirimycin, the
conversion of the G protein into an endo H- resistant form was completely
arrested. While the lack of G protein processing by CHO cells was
consistent with the absence of in vitro measured endomannosidase activity
in this cell line, the failure of MDBK and MDCK cells to convert the G
protein into an endo H-resistant form was surprising since these cell lines
have substantial levels of the enzyme. Similarly, we observed that
influenza virus hemagglutinin was not processed in castanospermine-treated
MDCK cells. Our findings suggest that studies which rely on glucosidase
inhibition to explore the function of glucose in controlling such critical
biological phenomena as intracellular movement or quality control should be
carried out in cell lines in which the glycoprotein under study is not a
substrate for endomannosidase action.
相似文献
2.
Background
Although cystic fibrosis is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, the severity of disease is highly variable indicating the influence of modifier genes. The intestines of Cftr deficient mice (CF mice: Cftr tm1Unc ) are prone to obstruction by excessive mucus accumulation and are used as a model of meconium ileus and distal intestinal obstruction syndrome. This phenotype is strongly dependent on the genetic background of the mice. On the C57Bl/6 background, the majority of CF mice cannot survive on solid mouse chow, have inflammation of the small intestine, and are about 30% smaller than wild type littermates. In this work potential modifier loci of the CF intestinal phenotype were identified.Results
CF mice on a mixed genetic background (95% C57Bl/6 and 5% 129Sv) were compared to CF mice congenic on the C57Bl/6 background for several parameters of the intestinal CF phenotype. CF mice on the mixed background exhibit significantly greater survival when fed dry mouse chow, have reduced intestinal inflammation as measured by quantitative RT-PCR for marker genes, have near normal body weight gain, and have reduced mucus accumulation in the intestinal crypts. There was an indication of a gender effect for body weight gain: males did not show a significant improvement at 4 weeks of age, but were of normal weight at 8 weeks, while females showed improvement at both 4 and 8 weeks. By a preliminary genome-wide PCR allele scanning, three regions were found to be potentially associated with the milder phenotype. One on chr.1, defined by marker D1Mit36, one on chr. 9 defined by marker D9Mit90, and one on chr. 10, defined by marker D10Mit14.Conclusion
Potential modifier regions were found that have a positive impact on the inflammatory phenotype of the CF mouse small intestine and animal survival. Identification of polymorphisms in specific genes in these regions should provide important new information about genetic modifiers of the CF intestinal phenotype. 相似文献3.
Phylogeny of the M superhaplogroup inferred from complete mitochondrial genome sequence of Indian specific lineages
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Revathi Rajkumar Jheelam Banerjee Hima Bindu Gunturi R Trivedi VK Kashyap 《Genome biology》2004,6(2):P3
Background
Phylogenetic analysis of human complete mitochondrial DNA sequences has largely contributed to resolving phylogenies and antiquity of different lineages belonging to the majorhaplogroups L, N and M (East-Asian lineages). In the absence of whole mtDNA sequence information of M lineages reported in India that exhibits highest diversity within the sub-continent, the present study was undertaken to provide a detailed analysis of this haplogroup to precisely characterize the lineages and unravel their intricate phylogeny. 相似文献4.
A Puri R Sethi B Singh SK Dwivedi VS Narain RK Saran VK Puri 《Indian pacing and electrophysiology journal》2009,9(3):186-189
A 25-year-old previously asymptomatic pregnant woman at 36 weeks'' gestation was noticed to have repetitive monomorphic ventricular tachycardia. A dilated left ventricle with moderately reduced systolic function was found on echocardiographic examination. This is a very rare presentation of peripartum cardiomyopathy (PPCMP) presenting with repetitive monomorphic ventricular tachycardia. 相似文献
5.
6.
A Rajor R Sharma VK Sood Dr V Ramamurthy 《Journal of industrial microbiology & biotechnology》1996,16(4):237-240
Sawdust, a bulky waste generated by wood processing industries, has very few profitable and ecofriendly uses and poses a problem of proper disposal. Treatment with the fungusVolvariella volvaceae and a dilute solution of urea converted sawdust from a phytoinhibitory material to a phytostimulatory soil conditioner. In different types of soils, the soil conditioner increased the moisture retention and facilitated the cohesive interaction of particles. Analyses of the major biopolymers of sawdust after fungal treatment indicated that levels of cellulose, hemicellulose and lignin decreased; however, these changes did not account for the plant growth stimulatory property attained by this material. 相似文献
7.
Pei-Lung Chen Dimitrios Avramopoulos Virginia K. Lasseter John A. McGrath M. Daniele Fallin Kung-Yee Liang Gerald Nestadt Ningping Feng Gary Steel Andrew S. Cutting Paula Wolyniec Ann E. Pulver David Valle 《American journal of human genetics》2009,84(1):21-34
Linkage studies have implicated 10q22-q23 as a schizophrenia (SZ) susceptibility locus in Ashkenazi Jewish (AJ) and Han Chinese from Taiwan populations. To further explore our previous linkage signal in the AJ population (NPL score: 4.27, empirical p = 2 × 10−5), we performed a peakwide association fine mapping study by using 1414 SNPs across ~12.5 Mb in 10q22-q23. We genotyped 1515 AJ individuals, including 285 parent-child trios, 173 unrelated cases, and 487 unrelated controls. We analyzed the binary diagnostic phenotype of SZ and 9 heritable quantitative traits derived from a principal components factor analysis of 73 items from our consensus diagnostic ratings and direct assessment interviews. Although no marker withstood multiple test correction for association with the binary SZ phenotype, we found strong evidence of association by using the “delusion” factor as the quantitative trait at three SNPs (rs10883866, rs10748842, and rs6584400) located in a 13 kb interval in intron 1 of Neuregulin 3 (NRG3). Our best p value from family-based association analysis was 7.26 × 10−7. We replicated this association in the collection of 173 unrelated AJ cases (p = 1.55 × 10−2), with a combined p value of 2.30 × 10−7. After performing 10,000 permutations of each of the phenotypes, we estimated the empirical study-wide significance across all 9 factors (90,000 permutations) to be p = 2.7 × 10−3. NRG3 is primarily expressed in the central nervous system and is one of three paralogs of NRG1, a gene strongly implicated in SZ. These biological properties together with our linkage and association results strongly support NRG3 as a gene involved in SZ. 相似文献
8.
Genomewide linkage scan for schizophrenia susceptibility loci among Ashkenazi Jewish families shows evidence of linkage on chromosome 10q22 总被引:3,自引:0,他引:3
Fallin MD Lasseter VK Wolyniec PS McGrath JA Nestadt G Valle D Liang KY Pulver AE 《American journal of human genetics》2003,73(3):601-611
Previous linkage studies in schizophrenia have been discouraging due to inconsistent findings and weak signals. Genetic heterogeneity has been cited as one of the primary culprits for such inconsistencies. We have performed a 10-cM autosomal genomewide linkage scan for schizophrenia susceptibility regions, using 29 multiplex families of Ashkenazi Jewish descent. Although there is no evidence that the rate of schizophrenia among the Ashkenazim differs from that in other populations, we have focused on this population in hopes of reducing genetic heterogeneity among families and increasing the detectable effects of any particular locus. We pursued both allele-sharing and parametric linkage analyses as implemented in Genehunter, version 2.0. Our strongest signal was achieved at chromosome 10q22.3 (D10S1686), with a nonparametric linkage score (NPL) of 3.35 (genomewide empirical P=.035) and a dominant heterogeneity LOD score (HLOD) of 3.14. Six other regions gave NPL scores >2.00 (on chromosomes 1p32.2, 4q34.3, 6p21.31, 7p15.2, 15q11.2, and 21q21.2). Upon follow-up with an additional 23 markers in the chromosome 10q region, our peak NPL score increased to 4.27 (D10S1774; empirical P=.00002), with a 95% confidence interval of 12.2 Mb for the location of the trait locus (D10S1677 to D10S1753). We find these results encouraging for the study of schizophrenia among Ashkenazi families and suggest further linkage and association studies in this chromosome 10q region. 相似文献
9.
Background
The Kuki-Chin-Mizo population comprising traditionally endogamous tribal groups residing in the state of Mizoram, India claim their descent from the ten lost tribes of Israel that were exiled by the Assyrians. To ascertain their oral history, we analysed DNA markers comprising 15 autosomal microsatellite markers, 5 biallelic and 20 microsatellite markers on Y-chromosome and the maternally inherited mitochondrial DNA sequence variations on 414 individuals belonging to 5 tribal communities from Mizoram (Hmar, Kuki, Mara, Lai and Lusei). The genetic profiles obtained were compared either with populations sharing Jewish ancestry or with local populations along the probable route of migration of the Jewish ancestry claimant Mizoram tribes. 相似文献10.
Revathi Rajkumar Jheelam Banerjee Hima Bindu Gunturi R Trivedi VK Kashyap 《Genome biology》2005,6(2):1-23