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Teresa Fazia Daria Marzanati Anna Laura Carotenuto Ashley Beecham Athena Hadjixenofontos Jacob L. McCauley Valeria Saddi Marialuisa Piras Luisa Bernardinelli Davide Gentilini 《Current issues in molecular biology》2021,43(3):1778
Multiple Sclerosis (MS) is a complex multifactorial autoimmune disease, whose sex- and age-adjusted prevalence in Sardinia (Italy) is among the highest worldwide. To date, 233 loci were associated with MS and almost 20% of risk heritability is attributable to common genetic variants, but many low-frequency and rare variants remain to be discovered. Here, we aimed to contribute to the understanding of the genetic basis of MS by investigating potentially functional rare variants. To this end, we analyzed thirteen multiplex Sardinian families with Immunochip genotyping data. For five families, Whole Exome Sequencing (WES) data were also available. Firstly, we performed a non-parametric Homozygosity Haplotype analysis for identifying the Region from Common Ancestor (RCA). Then, on these potential disease-linked RCA, we searched for the presence of rare variants shared by the affected individuals by analyzing WES data. We found: (i) a variant (43181034 T > G) in the splicing region on exon 27 of CUL9; (ii) a variant (50245517 A > C) in the splicing region on exon 16 of ATP9A; (iii) a non-synonymous variant (43223539 A > C), on exon 9 of TTBK1; (iv) a non-synonymous variant (42976917 A > C) on exon 9 of PPP2R5D; and v) a variant (109859349-109859354) in 3′UTR of MYO16. 相似文献
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Tumorigenicity of EJ-ras oncogene transformed NIH 3T3 cells and expression of plasminogen activators
M K Sidhu M S Russo K A Zirvi L Scala S Kumar 《Cell biology international reports》1990,14(6):527-542
A number of clonal cell lines have been isolated from NIH 3T3 cells transfected with the plasmid, pSV2 gpt-EJ-ras. The plasmid expresses Val12 instead of Gly12 in p21 ras protein and can be selected for the expression of E. coli XGPRT gene in mammalian cells. Southern analyses of the Eco R1 and Bam H1 digests of chromosomal DNA shows that multiple copies of the plasmid are integrated in a tandem sequence in the clones used in this study. The transfectants showed refractile appearance and criss-crossed pattern of growth, exhibited elevated expression of ras mRNA and formed tumors in nude mice commensurate with the copy number of the integrated EJ-ras gene. The increased propensity to form tumors did not correlate with the expression of urinary or tissue plasminogen activators (u-PA or t-PA). The cellular and secreted activity of u-PA in fact decreased as the ras gene expression increased. These data show that the enhanced tumorigenicity of transformed murine cells is related to the tandem integration and expression of human EJ-ras. The overexpression of ras has very little effect on t-PA but appears to suppress u-PA activity. 相似文献
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Anthony R. Russo 《International Review of Hydrobiology》1984,69(4):521-528
The spatial patterns of sea anemones (genus: Anthopleura) were analyzed off the rocky intertidal of California. A. elegantissima partitions space in a regular or even pattern and interferes with conspecifics. Its associate A. xanthogrammica shows no signs of interference with conspecifics or congenerics and displays a clumped spatial distribution. 相似文献
998.
Even though Au crystallizes only as a simple FCC structure in bulk there have been many different and fascinating structures discovered experimentally for Au on the nanoscale. Unfortunately, for Au a direct ab-initio approach in studying dynamic growth mechanisms of nanostructures is prohibitively expensive from a computational perspective, so here we use methods based on accurate semi-empirical, many-body potentials whose parameters are obtained from a combination of empirical and ab-initio data as a viable alternative. We show that this method when combined with molecular dynamics may be used to simulate the growth of Au particles in a bath of solvent atoms (either in a gaseous or liquid state) which results in structures of a range of different morphologies. An analysis of the results indicates what characteristics of the solvent and its interactions are important in determining these different morphologies. 相似文献
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Valeria Silva-álvarez Gisela R. Franchini Jorge L. Pórfido Malcolm W. Kennedy Ana M. Ferreira Betina Córsico 《PLoS neglected tropical diseases》2015,9(3)
BackgroundThe hydatid disease parasite Echinococcus granulosus has a restricted lipid metabolism, and needs to harvest essential lipids from the host. Antigen B (EgAgB), an abundant lipoprotein of the larval stage (hydatid cyst), is thought to be important in lipid storage and transport. It contains a wide variety of lipid classes, from highly hydrophobic compounds to phospholipids. Its protein component belongs to the cestode-specific Hydrophobic Ligand Binding Protein family, which includes five 8-kDa isoforms encoded by a multigene family (EgAgB1-EgAgB5). How lipid and protein components are assembled into EgAgB particles remains unknown. EgAgB apolipoproteins self-associate into large oligomers, but the functional contribution of lipids to oligomerization is uncertain. Furthermore, binding of fatty acids to some EgAgB subunits has been reported, but their ability to bind other lipids and transfer them to acceptor membranes has not been studied.Conclusions/SignificanceWe show that EgAgB apolipoproteins can oligomerize in the absence of lipids, and can bind and transfer fatty acids to phospholipid membranes. Since imported fatty acids are essential for Echinococcus granulosus, these findings provide a mechanism whereby EgAgB could engage in lipid acquisition and/or transport between parasite tissues. These results may therefore indicate vulnerabilities open to targeting by new types of drugs for hydatidosis therapy. 相似文献
1000.
Gamma Interferon Is a Major Suppressive Factor Produced by Activated Human Peripheral Blood Lymphocytes That Is Able To Inhibit Foamy Virus-Induced Cytopathic Effects
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Valeria Falcone Matthias Schweizer Antonio Toniolo Dieter Neumann-Haefelin Andreas Meyerhans 《Journal of virology》1999,73(2):1724-1728
The activation of human peripheral blood lymphocytes by mitogens or by triggering the T-cell receptor with anti-CD3 antibodies leads to the production of a potent soluble inhibitory activity against foamy virus-induced cytopathic effects in vitro. The inhibitory activity acts in a species-specific manner. As a consequence, the isolation of foamy viruses from blood lymphocytes of infected humans is accelerated in a heterologous coculture system. Antibodies against gamma interferon (IFN-γ) are able to suppress most of the inhibitory activity, suggesting that IFN-γ is the dominant component. 相似文献