1,721,055 research outputs found
Going Beyond Counting First Authors in Author Co-citation Analysis
The 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
“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
We 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
Analysis of mRNA 3' tagging pathway components
RNA stability and translational repression have become a major area of scientific interest with relevance to a wide range of biological processes including quality control mechanisms and gene regulation. Currently, the molecular events that determine when an actively translating transcript is silenced are not fully understood. In this thesis we investigated the link between mRNA degradation and translational repression, investigating one of the eukaryotic signals that designate transcripts for degradation and translational repression. This work is focused on A. nidulans, a versatile, well developed model system which has been used extensively. Importantly, with respect to this study many pathways involved in RNA 3’ modification being studies are conserved with animal and plant systems, unlike the major model fungal system, Saccharomyces cerevisiae. Recent data suggests the addition of a pyrimidine tag to the transcripts 3’ end promotes ribosome dissociation and mRNA degradation. In this thesis we designed a protocol for the heterologous expression and purification of two ribonucleotidyl proteins, CutA and CutB, which are responsible for 3’ pyrimidine tagging. Characterisation of the enzyme activity of these two enzymes in vitro was consistent with in vivo analysis; CutA showing that it prefers CTP over UTP as a substrate, leading to the addition of a short tag of 1-3 nucleotides to an A15 mRNA oligomer. In the case of CutB preliminary data suggested a likely similarity with CutA. Interestingly, with ATP as a substrate both CutA and CutB are highly processive, leading to rapid polyadenylation of the A15 RNA in vitro. This activity was recently observed in vivo, determining a preliminary result for understanding a possible role of CutA and CutB in cytoplasmic mRNA transcript reactivation. The presence of different combinations of nucleotides resulted in the addition of only short 3’ tags, consistent with in vitro data using different RNA targets, which indicates that the terminal nucleotide significantly affects the enzyme activity, such that terminal cytosines and urydines interrupt the adenylation activity. Furthermore, we characterised the eRF1-eRF3 termination complex and the Upf1 helicase from A. nidulans, in order to preliminary understand their role in triggering CutA and CutB tagging by creating an in vitro mRNA surveillance complex. Additionally, we designed a protocol for the purification of A. nidulans ribosomes, and solved the structure of the wild type 70S ribosome from A. nidulans, using cryo-electron microscopy. Within the ribosomal study, we described preliminary evidence for an ubiquitination dependent, ribosome recycle pathway. This involved studying the ribosomes of A. nidulans strains disrupted for Lsm1 and
Dcp1, both of which are involved in mRNA decapping. The development of protocols for the purification of ribosomes and various protein factors involved in a surveillance complex, and the in vitro characterisation of CutA and CutB activities, represents a significant step toward understanding the functional links between specific proteins and the ribosome termination complex in RNA tagging and its role in modulating RNA stability and facilitating dissociation of stalled termination complexes
Dispelling the Myths Behind First-author Citation Counts
We 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
Investigating the role of host TTR-RBPs during SFV4 and MHV-68 infection
The stability and translation of messenger RNA (mRNA) in a cell is partially controlled by an array of turnover and translation regulatory RNA-binding proteins (TTR-RBPs). These proteins bind to the untranslated regions (UTRs) and poly(A) tail of mRNA and facilitate its processing, nuclear export, turnover and translation. Interestingly, a diverse range of viruses utilise different host TTR-RBPs to facilitate infection of host cells.
Human antigen R (HuR) is a TTR-RBP which binds uracil rich sequences in mRNA, leading to increased mRNA stability and translation. Mammalian HuR has been shown to bind RNA sequences rich in uracil in the 3’UTR of a range of alphavirus genomes. Disruption of this interaction via deletion of the HuR binding sequences in the viral genome or knock-down of HuR by RNAi has been to shown to significantly decrease virus titre during Sindbis virus (SINV) infection of mammalian cells. Semliki Forest virus (SFV) genomic RNA also binds HuR via a uracil rich element (URE) and a conserved sequence element (CSE) at the 3’ of its 3’UTR.
The main aim of this study was to investigate the significance of the URE and CSE of the SFV4 3’UTR during SFV4 infection of mammalian cells. This was achieved by engineering rSFV4 mutants with deletions of the URE and CSE from the SFV4 3’UTR and a rSFV4 with an additional four UREs in its 3’UTR. These rSFV4 mutants also expressed a reporter protein, either eGFP or Guassia luciferase for detection by confocal imaging and analysis of replication by luciferase assay, respectively.
Akin to infection with SINV, this study identified that during infection of mammalian cells with SFV4, host HuR translocates from the nucleus to the cytoplasm. Infection of NIH/3T3 cells with rSFV4 lacking the URE in its 3’UTR resulted in significantly less HuR relocalising to the cytoplasm. A concurrent reduction in infectious virions, a reduction in viral RNA abundance, and a reduction in viral gene expression was also observed. In comparison, an addition of four UREs to the SFV4 3’UTR, increased the rate and amount of HuR relocalising to the cytoplasm post-infection, increased the concentration of infectious virions, increased viral RNA abundance and increased viral gene expression. These results suggest a significant role for the URE of the SFV4 3’UTR during infection in mammalian cells and suggest that the interaction between the URE of SFV4 and host HuR may, at least in part, be responsible for this effect.
Mammalian cytoplasmic poly(A) binding protein (PABPC) protects mRNA transcripts from deadenylation and 3’ end degradation, facilitates mRNA nuclear export and mRNA translation. Infection of mammalian cells with the gammaherpesviruses of the Herpesviridae family results in the striking nuclear influx of PABPC from the cytoplasm. During lytic infection of mammalian cells with murine gammaherpevirus 68 (MHV-68) the viral protein muSOX elicits shut-off of host gene expression. This is achieved by the degradation of bulk host mRNA via an incompletely understood mechanism. The expression of muSOX on a transfected expression plasmid also results in the nuclear influx of PABPC suggesting a possible link between host shut-off and the nuclear influx of host PABPC.
The secondary aim of this study was to investigate the role that PABPC may play during the host shut-off of gene expression elicited by the viral muSOX protein during MHV-68 infection. To investigate this, an MHV-68 mutant encoding muSOX with a premature stop codon (MHV-68 ORF37stop) was utilised. This study found that the nuclear influx of PABPC during infection of mammalian cells with MHV-68 occurred gradually over the course of lytic infection and did not occur during infection with MHV-68 ORF37stop virus. Since gradual nuclear influx of PABPC occurs in mammalian cells following a block in mRNA nuclear export, the possibility of MHV-68 causing a block in mRNA nuclear export was investigated. By separation of the nuclear and cytoplasmic fractions post-infection and analysis of host mRNA abundance by RT-qPCR, no block in mRNA nuclear export was detected during MHV-68 infection despite PABPC relocalising to the nucleus.
The roles which TTR-RBPs play during infection of host cells with a range of viruses are still being fully elucidated. These results suggest that HuR plays a significant role during Semliki Forest virus infection of mammalian cells and proposes HuR and other TTR-RBPs as novel targets for antiviral drugs
An examination of the endoplasmic reticulum stress response in the filamentous fungus Aspergillus nidulans
Abstract
Filamentous fungi are used throughout the biotechnology industry for the production of both native and recombinant proteins. There is a marked difference in the level of recombinant protein production compared to native, with yields decreasing from grams to milligrams per litre. The endoplasmic reticulum stress response (ERSR) has been identified as a potential bottleneck for recombinant protein production. In higher eukaryotes the ERSR has three known sensors, ire1, perk and atf6. Through these sensors, ER stress is attenuated by upregulation of ERSR target genes, global translational repression and degradation of transcripts targeted to the ER. Fungi have only one confirmed sensor of the higher eukaryotic ERSR, coordinated by the functional homologue of ire1 (ireA) which induces the ERSR through activation of the transcription factor HacA. In this study, I examine the ERSR of the filamentous fungi Aspergillus nidulans, a model organism for Aspergillus spp, to elucidate the fungal ERSR in an attempt to identify targets for increased recombinant protein production (RPP) yields. In this thesis I show that IreA is required for viability outwith its role in HacA activation as overexpression of the TF did not recover a ΔireA strain’s lethal phenotype. Also, that during ER stress, IreA is required for degradation of two transcripts encoding ER processed proteases as is observed in higher eukaryotes. I provide evidence for a second transcriptional pathway regulating gene expression during ER stress in A. nidulans. Further to this, polysome profiling has shown global translational repression during ER stress similar to that observed in higher eukaryotes. The findings of this research project are that the fungal ERSR is more conserved with that of higher eukaryotes than previously assumed, providing several new targets to potentially increase recombinant protein production (RPP)
koamabayili/VECTRON-author-checklist: VECTRON author checklist
We 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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