1,720,957 research outputs found
Structure and Function of Multimeric BTB Proteins and Cullin3 Substrate Adaptors
No full textOligomerization and ubiquitylation are fundamental to the function of many proteins. Protein oligomerization confers numerous advantages including allosteric regulation, increased coding efficiency, and reduced transcriptional and translational error rates. Ubiquitylation is a widespread post-translational modification that targets modified proteins to a variety of fates including degradation by the 26S proteasome. Dysfunctional protein degradation is a common mechanism shared by a diverse range of human diseases.
Many members of the BTB domain superfamily have roles centered on protein oligomerization and ubiquitylation. The BTB domain can facilitate self-assembly to form dimers, tetramers, and pentamers. In addition, many BTB proteins provide substrate specificity for the Cullin3 (Cul3) E3 ubiquitin ligase. Dysfunctional BTB/Cullin3 ubiquitinylation complexes are involved in certain forms of prostate cancer, medulloblastoma, hereditary hypertension and other diseases. Thus, understanding the details of BTB protein oligomerization and Cul3 interaction is important towards many aspects of human disease.
The research presented in this thesis addresses several areas of BTB/Cul3 biology. The mechanism of dimeric BTB protein to Cul3 association was expanded to include the contributions from the BACK domain observed in the crystal structure of KLHL3/Cul3. Several KLHL3 mutations associated with familial hypertension were found to disrupt Cul3 binding. Next, the structure and oligomeric state of several KCTD family BTB proteins were investigated and found to be pentameric instead of tetrameric. The Cul3 binding properties of several KCTD proteins were characterized and found to be heterogeneous in contrast to other BTB protein families. The structural and functional properties of several KCTD proteins were used to propose a mechanism of KCTD/Cul3 association and the determinants for Cul3 binding. Finally, the structure of the KCTD5/Cul3/Gβγ complex was characterized and the binding affinities of Cul3 and Gβγ to KCTD5 were determined. Overall, these results provide insight into the assembly of multimeric BTB/Cul3 ubiquitylation complexes.Ph.D.2019-03-02 00:00:0
Structure and Function of Multimeric BTB Proteins and Cullin3 Substrate Adaptors
Get PDFOligomerization and ubiquitylation are fundamental to the function of many proteins. Protein oligomerization confers numerous advantages including allosteric regulation, increased coding efficiency, and reduced transcriptional and translational error rates. Ubiquitylation is a widespread post-translational modification that targets modified proteins to a variety of fates including degradation by the 26S proteasome. Dysfunctional protein degradation is a common mechanism shared by a diverse range of human diseases.
Many members of the BTB domain superfamily have roles centered on protein oligomerization and ubiquitylation. The BTB domain can facilitate self-assembly to form dimers, tetramers, and pentamers. In addition, many BTB proteins provide substrate specificity for the Cullin3 (Cul3) E3 ubiquitin ligase. Dysfunctional BTB/Cullin3 ubiquitinylation complexes are involved in certain forms of prostate cancer, medulloblastoma, hereditary hypertension and other diseases. Thus, understanding the details of BTB protein oligomerization and Cul3 interaction is important towards many aspects of human disease.
The research presented in this thesis addresses several areas of BTB/Cul3 biology. The mechanism of dimeric BTB protein to Cul3 association was expanded to include the contributions from the BACK domain observed in the crystal structure of KLHL3/Cul3. Several KLHL3 mutations associated with familial hypertension were found to disrupt Cul3 binding. Next, the structure and oligomeric state of several KCTD family BTB proteins were investigated and found to be pentameric instead of tetrameric. The Cul3 binding properties of several KCTD proteins were characterized and found to be heterogeneous in contrast to other BTB protein families. The structural and functional properties of several KCTD proteins were used to propose a mechanism of KCTD/Cul3 association and the determinants for Cul3 binding. Finally, the structure of the KCTD5/Cul3/Gβγ complex was characterized and the binding affinities of Cul3 and Gβγ to KCTD5 were determined. Overall, these results provide insight into the assembly of multimeric BTB/Cul3 ubiquitylation complexes.Ph.D.2019-03-02 00:00:0
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
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
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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