1,720,953 research outputs found
Structure-function analysis of the small heat shock protein sequestrase Hsp42 from Saccharomyces cerevisiae
No full textCells have evolved a complex network of mechanisms to maintain protein homeostasis.
Among these, protein sequestration executed by small heat shock proteins (sHsps) serves as a
strategy to prevent deleterious aggregation by capturing misfolded proteins into complexes
that remain amenable to disaggregation by ATP-dependent chaperones. The size and
morphology of these complexes are determined by the sHsp involved, the substrate, and the
aggregation conditions. Some sHsps form only small, soluble assemblies (holdase activity),
while others additionally generate large, microscopically visible inclusions (aggregase
activity). The precise mechanisms governing the architecture of these complexes remain
incompletely understood.
In this study, I investigated the structure and function of the Saccharomyces cerevisiae sHsp
Hsp42, which exhibits both holdase and aggregase activities. Hsp42 is distinguished from
other sHsps by an extended intrinsically disordered N-terminal region, which comprises a
prion-like domain (PrLD) and a classical intrinsically disordered domain (IDD), defined by
their amino acid composition. To dissect the structural organization of Hsp42, I employed a
combination of biophysical, microscopic, and computational approaches. My data reveal that
Hsp42 assembles into a range of oligomeric states, from dimers to decamers, with octamers
being the predominant species. This oligomerization is dynamic and responsive to
environmental triggers such as temperature and pH. Additionally, Hsp42 undergoes extremely
rapid subunit exchange, a feature critical for its chaperone function.
Structural modeling predicts that Hsp42 forms planar ring-like octamers made of folded
domains, flanked by disordered regions extending outward. This novel arrangement of ACDs
in sHsp was never reported in other sHsps. This model was partially validated by cross-linking
mass spectrometry, which identified proximity regions within the oligomer, and by limited
proteolysis coupled to mass spectrometry, which identified exposed and protected regions.
I further demonstrate that Hsp42 forms substrate-dependent complexes of varying size. Cross�linking mass spectrometry identified multiple substrate-binding regions within Hsp42.
Importantly, my findings confirm that Hsp42 and bound substrate are not passively released
from these complexes and that complex dissolution requires the coordinated action of the
Hsp70/Hsp40/Hsp100 disaggregation machinery.
Finally, I dissected the contributions of PrLD, IDD, and other domains and conserved motifs
of Hsp42 to substrate sequestration and recovery. Using a series of deletion and point mutants,
I show that distinct domains of Hsp42 mediate substrate interaction and complex formation,
with the PrLD playing a central role – its deletion markedly reduced chaperone activity. In
contrast, other domains are required for efficient substrate handover to the disaggregase
system. The IDD was found to be essential for forming large Hsp42-substrate complexes and
to confer temperature-dependent aggregase activity. Moreover, the IDD appears to influence
complex architecture in a manner that facilitates access by Hsp70, while blocking access by
standalone Hsp100 disaggregase
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
Full text link“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
Full text linkWe 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
Full text linkWe 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
Author Under Sail The Imagination of Jack London, 1893-1902
No full textIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Intro -- Title Page -- Copyright Page -- Dedication -- Contents -- Acknowledgments -- Introduction -- 1. Spirit Truth -- 2. From Absorption to Theatricality and Back Again -- 3. "I Will Build a New Present" -- 4. Sons as Authors -- 5. Fathers as Publishers -- 6. The Daughter as Author -- 7. Lovers as Authors -- 8. At Sea with the Family -- 9. Yellow News, Yellow Stories -- 10. The Return Home -- Notes -- Bibliography -- Index -- About Jay WilliamsIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Description based on publisher supplied metadata and other sources.Electronic reproduction. Ann Arbor, Michigan : ProQuest Ebook Central, YYYY. Available via World Wide Web. Access may be limited to ProQuest Ebook Central affiliated libraries
- …
