1,720,954 research outputs found
Deciphering structural variations within the norovirus capsid
Get PDFNorovirus is one of the most common agents associated with acute gastroenteritis. Despite its
discovery 50 years ago, as of now there is no cure or treatment, and knowledge about the
infection cycle of norovirus is still limited.
Using cryo-electron microscopy, we determined the structure of different clinically relevant
GII.4 strain virus like particles (VLPs), and an engineered version of GII.4 that is in use as
vaccine candidate. Unexpectedly we found that these empty particles were composed of 240
copies of VP1 instead of the typical 180. We could show that this conformation is only
adopted by GII.4 strain VLPs, and that norovirus virions most likely assemble into T=3
icosahedral particles. Conversely, VP1 of GII.17, another strain that has become clinically
relevant in the last years, assembled into the characteristic T=3 icosahedral capsid, as
determined by cryo-electron microscopy.
Moreover, we characterized a panel of GII.4 specific Nanobodies and determined their
binding sites and influence on particle integrity using cryo-electron microscopy. Several
Nanobodies had a strong inhibition potential in surrogate assays against GII.4 VLPs, but
cross-reactivity to other strains was low. Structures of Nanobody/VLP complexes revealed
that the Nanobodies bound to a similar site on the lower part of the P domain. Moreover, the
structures showed that the P domains were flexibly rotated to distinct positions, but generally
particle conformation remained intact.
Likewise, we also worked on three GI.1 specific Nanobodies and found two Nanobodies with
great inhibition potential. Importantly, we found that combination of Nanobody with the
human milk oligosaccharide 2’FL was able to synergistically improve attachment inhibition
of VLPs to histo-blood group antigens, suggesting the use of combinational treatment against
norovirus infection.
In another study, we found that murine norovirus, which is commonly used as a model system
for human norovirus, is undergoing severe structural rearrangements after incubation with
ions, such as MgCl2 and CaCl2. The normally extended P domains are collapsing onto the
shell, accompanied by a rotational movement. Most likely, this movement is important to
facilitate infection. Importantly, we also characterized a Nanobody that was binding to the
lower part of the P domain, effectively inhibiting MNV infection by blocking this movement.
Taken together, these results broaden the understanding on general norovirus structure and
how noroviruses are interacting with antivirals and cofactors. Our basic research broadens the understanding of norovirus internal differences and capsid flexibilities, and can ultimately aid
in the development of a more effective treatment for norovirus infections
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
Natural extracts, honey, and propolis as human norovirus inhibitors
No full textNorovirus is the most important cause of acute gastroenteritis, yet there are still no antivirals, vaccines, or treatments available. Several studies have shown that norovirus-specific monoclonal antibodies, Nanobodies, and natural extracts might function as inhibitors. Therefore, the objective of this study was to determine the antiviral potential of additional natural extracts, honeys, and propolis samples. Norovirus GII.4 and GII.10 virus-like particles (VLPs) were treated with different natural samples and analyzed for their ability to block VLP binding to histo-blood group antigens (HBGAs), which are important norovirus co-factors. Of the 21 natural samples screened, date syrup and one propolis sample showed promising blocking potential. Dynamic light scattering indicated that VLPs treated with the date syrup and propolis caused particle aggregation, which was confirmed using electron microscopy. Several honey samples also showed weaker HBGA blocking potential. Taken together, our results found that natural samples might function as norovirus inhibitors
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
- …
