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proliferation and copy number variation of bel-like long terminal repeat retrotransposons within the diabrotica virgifera virgifera genome.the proliferation of retrotransposons within a genome can contribute to increased size and affect the function of eukaryotic genes. bel/pao-like long-terminal repeat (ltr) retrotransposons were annotated from the highly adaptable insect species diabrotica virgifera virgifera, the western corn rootworm, using survey sequences from bacterial artificial chromosome (bac) inserts and contigs derived from a low coverage next-generation genome sequence assembly. eleven unique d. v. virgifera bel elemen ...201324513336
serological evidence for multiple strains of canine norovirus in the uk dog population.noroviruses are associated with intestinal disease in humans, cows, pigs, mice, and, more recently, dogs. in 2007, the first canine norovirus (cnv) was identified and characterized in italy. subsequent studies have identified cnv in stools of dogs from portugal, greece, and the united states. to investigate the prevalence of cnv in the uk dog population, 228 canine stool samples were screened for cnv by qpcr, and 396 serum samples were screened for anti-cnv antibodies. qpcr of rna extracted from ...201324339947
the effect of functional mapkapk2 copy number variation cnv-30450 on elevating nasopharyngeal carcinoma risk is modulated by ebv infection.mitogen-activated protein kinase-activated protein kinase 2 (mapkapk2) is recognized as oncogenic and simulative role on tumorigenesis by virtue of abnormal expression in cancer including nasopharyngeal carcinoma (npc). we hypothesized that the copy number variation (cnv)-30450, which duplicates the mapkapk2 promoter, may affect mapkapk2 expression and be associated with npc risk. in two independent case-control panels of southern and eastern chinese with a total of 1590 npc patients and 1979 ca ...201424056810
characterization of dominant-negative and temperature-sensitive mutants of tombusvirus replication proteins affecting replicase assembly.the assembly of the viral replicase complex (vrc) on subcellular membranes is a key step in the replication process of plus-stranded rna viruses. in this work, we have identified lethal and temperature sensitive (ts) point mutations within the essential p33:p33/p92 interaction domain of p33 and p92 replication proteins of cucumber necrosis virus, a tombusvirus. mutations within the p33:p33/p92 interaction domain also affected viral rna recombination in yeast model host. an in vitro approach base ...201323332599
atomic structure of cucumber necrosis virus and the role of the capsid in vector transmission.cucumber necrosis virus (cnv) is a member of the genus tombusvirus and has a monopartite positive-sense rna genome packaged in a t=3 icosahedral particle. cnv is transmitted in nature via zoospores of the fungus olpidium bornovanus. cnv undergoes a conformational change upon binding to the zoospore that is required for transmission, and specific polysaccharides on the zoospore surface have been implicated in binding. to better understand this transmission process, we have determined the atomic s ...201324006433
micrornas in human lymphoblastoid cell lines.human lymphoblastoid cell lines (lcls) are generated by ebv-mediated b-cell transformation to provide unlimited genomic resources for human genetics and immunological studies. the lcl is a good in vitro cell model for assessing population differences in the basal expression of genes and mirnas as well as in cellular responses to various stimulators. recently, the utility of lcls was extended to pharmacogenomic studies to discover genetic factors underlying individual variations in response to ch ...201223140160
inhibition of choroidal and corneal pathologic neovascularization by plgf1-de gene transfer.ocular neovascularization (nv), the primary cause of blindness, typically is treated via inhibition of vegf-a activity. however, besides vegf-a, other proteins of the same family, including vegf-b and placental growth factor (plgf, all together vegfs), have a crucial role in the angiogenesis process. plgf and vegf, which form heterodimers if co-expressed, both are required for pathologic angiogenesis. we generated a plgf1 variant, named plgf1-de, which is unable to bind and activate vegfr-1, but ...201223139276
copy number variation in chemokine superfamily: the complex scene of ccl3l-ccl4l genes in health and disease.genome copy number changes (copy number variations: cnvs) include inherited, de novo and somatically acquired deviations from a diploid state within a particular chromosomal segment. cnvs are frequent in higher eukaryotes and associated with a substantial portion of inherited and acquired risk for various human diseases. cnvs are distributed widely in the genomes of apparently healthy individuals and thus constitute significant amounts of population-based genomic variation. human cnv loci are en ...201020659124
a non membrane-targeted human soluble cd59 attenuates choroidal neovascularization in a model of age related macular degeneration.age related macular degeneration (amd) is the most common cause of blindness amongst the elderly. approximately 10% of amd patients suffer from an advanced form of amd characterized by choroidal neovascularization (cnv). recent evidence implicates a significant role for complement in the pathogenesis of amd. activation of complement terminates in the incorporation of the membrane attack complex (mac) in biological membranes and subsequent cell lysis. elevated levels of mac have been documented o ...201121552568
Targeted decorin gene therapy delivered with adeno-associated virus effectively retards corneal neovascularization in vivo.Decorin, small leucine-rich proteoglycan, has been shown to modulate angiogenesis in nonocular tissues. This study tested a hypothesis that tissue-selective targeted decorin gene therapy delivered to the rabbit stroma with adeno-associated virus serotype 5 (AAV5) impedes corneal neovascularization (CNV) in vivo without significant side effects. An established rabbit CNV model was used. Targeted decorin gene therapy in the rabbit stroma was delivered with a single topical AAV5 titer (100 µl; 5×10 ...201122039486
macrophage activation associated with chronic murine cytomegalovirus infection results in more severe experimental choroidal neovascularization.the neovascular (wet) form of age-related macular degeneration (amd) leads to vision loss due to choroidal neovascularization (cnv). since macrophages are important in cnv development, and cytomegalovirus (cmv)-specific igg serum titers in patients with wet amd are elevated, we hypothesized that chronic cmv infection contributes to wet amd, possibly by pro-angiogenic macrophage activation. this hypothesis was tested using an established mouse model of experimental cnv. at 6 days, 6 weeks, or 12 ...201222570607
emergence of a viral rna polymerase variant during gene copy number amplification promotes rapid evolution of vaccinia virus.viruses are under relentless selective pressure from host immune defenses. to study how poxviruses adapt to innate immune detection pathways, we performed serial vaccinia virus infections in primary human cells. independent courses of experimental evolution with a recombinant strain lacking e3l revealed several high-frequency point mutations in conserved poxvirus genes, suggesting important roles for essential poxvirus proteins in innate immune subversion. two distinct mutations were identified ...201727928012
evidence that hsc70 is associated with cucumber necrosis virus particles and plays a role in particle disassembly.uncoating of a virus particle to expose its nucleic acid is a critical aspect of the viral multiplication cycle, as it is essential for the establishment of infection. in the present study, we investigated the role of plant hsp70 homologs in the uncoating process of cucumber necrosis virus (cnv), a nonenveloped positive-sense single-stranded rna [(+)ssrna] virus having a t=3 icosahedral capsid. we have found through western blot analysis and mass spectrometry that the hsp70 homolog hsc70-2 copur ...201727807229
biofilter as a functional annotation pipeline for common and rare copy number burden.recent studies on copy number variation (cnv) have suggested that an increasing burden of cnvs is associated with susceptibility or resistance to disease. a large number of genes or genomic loci contribute to complex diseases such as autism. thus, total genomic copy number burden, as an accumulation of copy number change, is a meaningful measure of genomic instability to identify the association between global genetic effects and phenotypes of interest. however, no systematic annotation pipeline ...201626776200
subretinal aav2.comp-ang1 suppresses choroidal neovascularization and vascular endothelial growth factor in a murine model of age-related macular degeneration.to assess whether tie2-mediated vascular stabilization ameliorates neovascular age-related macular degeneration (amd), we investigated the impact of adeno-associated virus-mediated gene therapy with cartilage oligomeric matrix protein angiopoietin-1 (aav2.comp-ang1) on choroidal neovascularization (cnv), vascular endothelial growth factor (vegf), and hypoxia-inducible factor (hif) in a mouse model of the disease. we treated mice with subretinal injections of aav2.comp-ang1 or control (aav2.acgfp ...201626775053
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