1,721,324 research outputs found
Small Heat Shock Proteins in Neurodegenerative Diseases.
No full textThe small heat shock proteins (sHSP) comprise 10 members in mammals where they are called the HspB proteins (HspB1-10). Like other HSP, the HspB proteins have chaperone activity in vitro. This activity is poorly characterized in vivo, however, many of these proteins protect cells against diverse stress and have been associated, in numerous studies, with protein conformation diseases. HspB proteins are upregulated in neurodegenerative disorders, including brain amyloidosis, and immunohistochemicalstudies showed that they are often trapped within proteininclusions that are formed in these diseases. Moreover, HspB proteins show a protective effect against protein aggregation and toxicity in cellular model of conformational diseases. Furthermore, mutations in four HspB proteins (HspB1, HspB4, HspB5 and HspB8) have been associated with neuromuscular and other protein conformation disorders. These observations constitute strong support for an important role of the HspB proteins in neurodegenerative disorders
Role of HspB1 and HspB8 in hereditary peripheral neuropathies: beyond the chaperone function
No full textWithin the last ten years, mutations in genes encoding the small heat shock proteins (also called HspB) HspB1, HspB4, HspB5 and HspB8 have been associated with neurological and muscular disorders. In particular, HspB1 and HspB8 mutations result in hereditary peripheral neuropathies, which primarily affect motor and/or sensory peripheral neurons. Due to their extremely long axons, peripheral neurons are particularly dependent on an efficient vesicular trafficking and axonal transport, whose defects have been directly linked to the development of hereditary peripheral neuropathies. Genetic analyses generated new insights into the molecular pathways involved in hereditary peripheral neuropathies, which include not only vesicular trafficking but also protein quality control, protein degradation and RNA processing. This review summarizes the current understanding of HspB implication in motor diseases, starting with a general picture of HspB functions followed by a description of new emerging roles for HspB1 and HspB8 in axonal transport, protein sorting and degradation
HspB8 and Bag3: A new chaperone complex targeting misfolded proteins to macroautophagy
No full textProtein quality control involves molecular chaperones that recognize misfolded proteins thereby preventing their aggregation, and associated co-chaperones that modulate substrate sorting between renaturation and proteasomal degradation. We recently described a new chaperone complex that stimulates degradation of protein substrates by macroautophagy. The complex is formed of HspB8, a member of the HspB family of molecular chaperones, which is found mutated in neuromuscular diseases, and Bag3, a member of the co-chaperone family of Bag domain-containing proteins. In this complex, Bag3 was shown to be responsible for macroautophagy stimulation. Here we analyzed the role of the three Bag3 canonical protein interaction domains. We show that the proline-rich region is essential for the Bag3-mediated stimulation of mutated huntingtin clearance. Surprisingly, deletion of the BAG domain that mediates Bag3 interaction with Hsp70 and Blc-2, did not affect its activity. We propose that in the HspB8- Bag3 complex, HspB8 is responsible for recognizing the misfolded proteins whereas Bag3, at least in part through its proline-rich domain, might recruit and activate the macroautophagy machinery in close proximity to the chaperone-loaded substrates
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
Regional differences in intrinsic PEEP (PEEPi) elucidated by direct measurement of alveolar pressure
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