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1.
Herpes simplex virus type 1 glycoprotein C-negative mutants exhibit multiple phenotypes, including secretion of truncated glycoproteins 总被引:39,自引:33,他引:6 下载免费PDF全文
A virus-neutralizing monoclonal antibody specific for glycoprotein C (gC) of herpes simplex virus type 1 strain KOS was used to select a number of neutralization-resistant mutants. A total of 103 of these mutants also were resistant to neutralization by a pool of gC-specific antibodies and thus were operationally defined as gC-. Analysis of mutant-infected cell mRNA showed that a 2.7-kilobase mRNA, comparable in size to the wild-type gC mRNA, was produced by nearly all mutants. However, six mutants, gC-5, gC-13, gC-21, gC-39, gC-46, and gC-98, did not produce the normal-size gC mRNA but rather synthesized a novel 1.1-kilobase RNA species. These mutants had deletions of 1.6 kilobases in the coding sequence of the gC structural gene, which explains their gC- phenotype. Despite the production of an apparently normal mRNA by the remaining 97 mutants, only 7 mutants produced a detectable gC polypeptide. In contrast to wild-type gC, which is a membrane-bound glycoprotein with an apparent molecular weight of 130,000 (130K), five of these mutants quantitatively secreted proteins of lower molecular weight into the culture medium. These were synLD70 (101K), gC-8 (109K), gC-49 (112K), gC-53 (108K), and gC-85 (106K). The mutant gC-3 secreted a protein that was indistinguishable in molecular weight from wild-type KOS gC. Another mutant, gC-44, produced a gC protein which also was indistinguishable from wild-type gC by molecular weight and which remained cell associated. Pulse-labeling of infected cells in the presence and absence of the glycosylation inhibitor tunicamycin demonstrated that these proteins were glycosylated and provided estimates of the molecular weights of the nonglycosylated primary translation products. The smallest of these proteins was produced by synLD70 and was 48K, about two-thirds the size of the wild-type polypeptide precursor (73K). Physical mapping of the mutations in synLD70 and gC-8 by marker rescue placed these mutations in the middle third of the gC coding sequence. Mapping of the mutations in other gC- mutants, including two in which no protein product was detected, also placed these mutations within or very close to the gC gene. The biochemical and genetic data available on mutants secreting gC gene products suggest that secretion is due to the lack of a functional transmembrane anchor sequence on these mutant glycoproteins. 相似文献
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Bloom Syndrome and Maternal Uniparental Disomy for Chromosome 15 总被引:4,自引:1,他引:3
Trevor Woodage Madhuri Prasad Joanne W. Dixon Roslyn E. Selby Dennis R. Romain Letizia M. Columbano-Green David Graham Peter K. Rogan James R. Seip Arabella Smith Ronald J. Trent 《American journal of human genetics》1994,55(1):74-80
Bloom syndrome (BS) is an autosomal recessive disorder characterized by increases in the frequency of sister-chromatid exchange and in the incidence of malignancy. Chromosome-transfer studies have shown the BS locus to map to chromosome 15q. This report describes a subject with features of both BS and Prader-Willi syndrome (PWS). Molecular analysis showed maternal uniparental disomy for chromosome 15. Meiotic recombination between the two disomic chromosomes 15 has resulted in heterodisomy for proximal 15q and isodisomy for distal 15q. In this individual BS is probably due to homozygosity for a gene that is telomeric to D15S95 (15q25), rather than to genetic imprinting, the mechanism responsible for the development of PWS. This report represents the first application of disomy analysis to the regional localization of a disease gene. This strategy promises to be useful in the genetic mapping of other uncommon autosomal recessive conditions. 相似文献
3.
While most research suggests mitochondrial DNA (mtDNA) harbors low or no methylation, a few studies claim to report evidence of high-level methylation in the mtDNA. The reasons behind these contradictory results are likely to be methodological but remain largely unexplored. Here, we critically reanalyzed a recent study by Patil et al. (2019) reporting extensive methylation in human mtDNA in a non-CpG context. Our analyses refute the original findings and show that these do not reflect the biology of the tested samples, but rather stem from a combination of methodological and technical pitfalls. The authors employ an oversimplified model that defines as methylated all reference positions with methylation proportions above an arbitrary cutoff of 9%. This substantially exacerbates the overestimation of methylated cytosines due to the selective degradation of unmethylated cytosine-rich regions. Additional limitations are the small sample sizes and lack of sample-specific controls for bisulfite conversion efficiency. In conclusion, using the same dataset employed in the original study by Patil et al., we find no evidence supporting the existence of extensive non-CpG methylation in the human mtDNA. 相似文献
4.
Pribat A Noiriel A Morse AM Davis JM Fouquet R Loizeau K Ravanel S Frank W Haas R Reski R Bedair M Sumner LW Hanson AD 《The Plant cell》2010,22(10):3410-3422
Tetrahydropterin-dependent aromatic amino acid hydroxylases (AAHs) are known from animals and microbes but not plants. A survey of genomes and ESTs revealed AAH-like sequences in gymnosperms, mosses, and algae. Analysis of full-length AAH cDNAs from Pinus taeda, Physcomitrella patens, and Chlamydomonas reinhardtii indicated that the encoded proteins form a distinct clade within the AAH family. These proteins were shown to have Phe hydroxylase activity by functional complementation of an Escherichia coli Tyr auxotroph and by enzyme assays. The P. taeda and P. patens AAHs were specific for Phe, required iron, showed Michaelian kinetics, and were active as monomers. Uniquely, they preferred 10-formyltetrahydrofolate to any physiological tetrahydropterin as cofactor and, consistent with preferring a folate cofactor, retained activity in complementation tests with tetrahydropterin-depleted E. coli host strains. Targeting assays in Arabidopsis thaliana mesophyll protoplasts using green fluorescent protein fusions, and import assays with purified Pisum sativum chloroplasts, indicated chloroplastic localization. Targeting assays further indicated that pterin-4a-carbinolamine dehydratase, which regenerates the AAH cofactor, is also chloroplastic. Ablating the single AAH gene in P. patens caused accumulation of Phe and caffeic acid esters. These data show that nonflowering plants have functional plastidial AAHs, establish an unprecedented electron donor role for a folate, and uncover a novel link between folate and aromatic metabolism. 相似文献
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Bouyoucos Ian A. Romain Martin Azoulai Lorine Eustache Kim Mourier Johann Rummer Jodie L. Planes Serge 《Coral reefs (Online)》2020,39(5):1209-1214
Coral Reefs - Sharks play important functional roles in coral reef ecosystems. Studying reef shark populations’ spatial ecology also contributes important data for effective conservation... 相似文献
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Cedric Minkin Lenny Blackman Jarrett Newbrey Selma Pokress Robert Posek Marlin Walling 《Biochemical and biophysical research communications》1977,76(3):875-881
Peritoneal mononuclear phagocytes elicited by thioglycollate demonstrate responsiveness to parathyroid hormone (PTH) and calcitonin (CT) which differs from that seen in the normal resident population. PTH causes a twofold stimulation of adenylate cyclase activity in elicited cells but inhibits this activity in resident cells. CT causes a greater stimulation of adenylate cyclase in elicited than in resident cells. Both CT and PTH cause an increase in cyclic AMP accumulation in cultures of elicited mononuclear phagocytes. These results indicate that cells of the mononuclear phagocyte lineage have functional receptors for both PTH and CT. This is the first biochemical evidence to support the hypothesis that mononuclear phagocytes are precursors of the bone resorbing osteoclast. 相似文献
10.
APS (adaptor protein with PH and SH2 domains) is an adaptor protein phosphorylated by several tyrosine kinase receptors including the insulin receptor. To identify novel binding partners of APS, we performed yeast two-hybrid screening. We identified Enigma, a PDZ and LIM domain-containing protein that was previously shown to be associated with the actin cytoskeleton. In HEK 293 cells, Enigma interacted specifically with APS, but not with the APS-related protein SH2-B. This interaction required the NPTY motif of APS and the LIM domains of Enigma. In NIH-3T3 cells that express the insulin receptor, Enigma and APS were partially co-localised with F-actin in small ruffling structures. Insulin increased the complex formation between APS and Enigma and their co-localisation in large F-actin containing ruffles. While in NIH-3T3 and HeLa cells the co-expression of both Enigma and APS did not modify the actin cytoskeleton organisation, expression of Enigma alone led to the formation of F-actin clusters. Similar alteration in actin cytoskeleton organisation was observed in cells expressing both Enigma and APS with a mutation in the NPTY motif. These results identify Enigma as a novel APS-binding protein and suggest that the APS/Enigma complex plays a critical role in actin cytoskeleton organisation. 相似文献