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Characterisation of a human herpesvirus 6 variant A 'amplicon' and replication modulation by U94-Rep 'latency gene'
No full textThe human herpesvirus 6 (HHV-6) variant A genome has conserved sequences which are signals for initiating lytic replication (origin, 'ori-lyt') and DNA packaging into the virion (pac2/1). Here these are functionally characterised and used to construct a gene-expression amplifiable-vector, an 'amplicon', with applications for gene delivery to lymphoid-myeloid cells or their progenitor stem cells. A minimal efficient ori-lyt for replication was identified which was enhanced in the presence of the imperfect direct repeated DNA domain (IDR). In A variant strains these are arranged as three adjacent repeats with the most divergence in IDR3. Addition of the pac2/1 sequences also enhanced detection of ori-lyt replication and conferred DNA packaging properties, thus, the amplicon could be packaged with 'helper' virus. An HHV-6 specific factor, which inhibits amplicon replication was identified by trans replication assays. This is the U94-Rep 'latency' gene product, which can modulate efficiency of such amplifiable vectors, based on the lytic origin. It could also affect maintenance of viral genomes or vectors during latency
Novel, nonconsensus cellular splicing regulates expression of a gene encoding a chemokine-like protein that shows high variation and is specific for human herpesvirus 6.
No full textThere are few genes that are specific and diagnostic for human herpesvirus-6. U83 and U22 are two of them. U22 is unique, whereas U83 encodes distant similarity with some cellular chemokines. Reverse transcription-polymerase chain reaction, cDNA cloning, and sequence analyses show polyadenylated RNA transcripts corresponding to minor full-length and abundant spliced forms of U83 in human herpesvirus 6-infected cells. The splice donor and acceptor sites do not fit consensus sequences for either major GT-AG or minor AT-AC introns. However, the spliced form can also be detected in a U83 transfected cell line; thus the novel sites are used by cellular mechanisms. This intron may represent a new minor CT-AC splicing class. The novel splicing regulates gene expression by introducing a central stop codon that abrogates production of the chemokine-like molecule, resulting in an encoded truncated peptide. The use of metabolic inhibitors and an infection time course showed expression of the two RNA transcripts with immediate early kinetics. However, the full-length product accumulated later, dependent on virus DNA replication, similar to U22. Sequence analyses of 16 strains showed high variation (13%) in U83, with conservation of the novel splice sites. Representative strain variants had similar kinetics of expression and spliced products
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Human Cytomegalovirus Transmission in Early Childhood and Impact of Maternal HIV in Zambia: A Molecular Study
Get PDFHuman cytomegalovirus (HCMV) is the leading infectious cause of birth defects and neurodevelopmental delay, with worst outcomes in congenital infection. HCMV exacerbates neurological disease and progression to AIDS in HIV co-infected infants. In Zambia HCMV has adverse effects on growth and development even in maternally HIV-exposed uninfected infants, affecting a third. Transmission to infants can be congenital or postnatal primarily through breast milk, similar to HIV. However, the route affecting infant development is not established, but critical to understand for deployment of appropriate interventions and hospital diagnostics. In this thesis, congenital HCMV infection was investigated in newborns using PCR and nucleotide sequencing of saliva and umbilical cord DNA, and showed 1% prevalence, which was too low to account for the widespread adverse growth effects. Therefore, maternal HCMV secretion via breast milk and the effects of maternal HIV were investigated. HCMV viral loads were measured by qPCR in 461 breast milk samples from both HIV-infected and uninfected mothers at postpartum day 3 and weeks 2, 4, 9, 12, and 16. Results showed higher HCMV viral loads and longer secretion in HIV-positive compared to negative mothers, peaking at week 4 (p=.026) and remaining elevated at week 16 (p<.001). HCMV strains were investigated using the hypervariable glycoprotein gO, with all eight genotypes detected, but no relationship to viral load. Next, Illumina NGS was used to further analyse strains and mixed infections in order to assess the burden of infection. A script was developed to identify linked gO and gN 'Molecular tags' via analyses of FASTQ reads. In 21 samples, mixed infections were identified, showing 1-7 genotypes and a dominant genotype constituting 45-100%. ZMB240, a full-length HCMV genome - the first reference strain from a healthy donor representing a transmission population, and also first from Africa - was derived directly from breast milk DNA and found similar to elsewhere, including the reference Merlin. Overall, the thesis provided evidence that breast milk is the principal route for early HCMV infection in breastfed Zambian infants, and that maternal HIV increases HCMV load, burden of infection, and duration of secretion in breast milk, thereby escalating and prolonging risk of early infant HCMV infection
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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