1,720,966 research outputs found
Proteostasis and Proteolysis
No full textProteins are the key decision-making workforce for practically all cellular signals. The precise equilibrium between protein translation, folding, function and timely degradation, also known as "proteostasis", determine cellular health as well as organismal maintenance and survival. Loss of cellular proteostasis is linked with physiological processes of deterioration such as aging, with conditions characterized by supraphysiological oxidative stress as well as with illness, including age-related diseases, neurodegeneration, inflammation, dystrophies and cancer. This book includes 18 chapters logically organized to allow comprehensive understanding of how maintenance of proteostasis protects cellular and organismal health, and how environmental and metabolic pressure can impair proteostasis and lead to disequilibrium and disease. Each chapter contains up-to-date information on its respective topic while some of them review the interplay of certain proteostatic mechanisms, a newly arising topic. Importantly, most chapters include tangible examples of how failure of proteostasis can underlie aging and disease. We hope that the compilation of the above topics will assist both novice and experienced researchers and students to become more familiar with the subject of proteostasis. In the long run, we hope that this book will inspire its readers and eventually promote new ideas and new research studies
Role of Sumoylation in Neurodegenerative Diseases and Inflammation
No full textSUMOylation, the post-translational attachment of the small ubiquitin-related modifier (SUMO) to target proteins, is essential for proper neuronal function and has emerged as a potential target in regulating Alzheimer's, Parkinson's and polyglutamine diseases. Many of the players in those diseases have been identified as SUMO substrates, like the amyloid precursor protein and tau, α-synuclein, huntingtin or ataxin-1 and -3. Aside from modifying key players in the neurodegenerative pathways, SUMO regulates inflammation and, more specifically, neuroinflammation mediated by astrocytes and microglia, which is frequently observed in neurodegenerative disorders. Here, we present recent insights into the roles for SUMOylation in these disorders, anticipating that emerging approaches to modify the SUMOylation pathway may be promising candidate therapies.MINECO/FEDER, EU (BFU2017- 84653-P)Severo Ochoa Excellence Program (SEV-2016-0644)UbiCODE Program (765445- EU)UBIRed Program (SAF2017-90900-REDT)Basque Country Government (IT1165-19)SPI 2018UE
S.cerevisiae as a tool to select inhibitors of the deneddylating activity of the COP9 signalome Angela Cirigliano, Sergio Menta, Mattia Mori, Valerio Licursi, Svetlana Danovska, Valentina Vapore, Giovanna Serino, Elah Pick, Bruno Botta, Rodolfo Negri, and Teresa Rinaldi
No full textThe COP9 signalosome (CSN) protein complex plays a key role in regulating cullin-RING ligases and is a central mediator of cellular functions essential for cancer progression. The CSN5/Jab1 gene, encoding the catalytic subunit of the complex, has been found amplified in many tumors; however, due to its pleiotropic effects, it has been difficult to dissect Csn5 function and its involvement in cancer progression. Moreover, while a growing body of evidence point to the neddylation pathway as a good target for drug development, specific inhibitors have not yet been developed for the Csn5 enzyme.
Deneddylation by the CSN is conserved in the budding yeast Saccharomyces cerevisiae and, in contrast to human or plants, lack of Csn5 does not compromise viability of budding yeast. We have recently performed a transcriptomic and proteomic analysis of a csn5 strain to assess its function in budding yeast, and we have shown that Csn5 is involved in the modulation of the genes controlling amino acid and lipid metabolism and in particular of the ergosterol biosynthesis; this observation correlates with lower ergosterol level in csn5 cells (Licursi et al., (2014). FEBS Journal, 281(1), 175-190)
In the study shown here, we have used budding yeast as a model to identify novel inhibitors of Csn5 deneddylating activity. We present our preliminary results obtained using a combined approach of molecular modelling and simple genetic tools to identify small molecules as selective inhibitors of Csn5 deneddylating functio
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
Yeast as a tool to select inhibitors of the cullin deneddylating enzyme Csn5
Get PDFThe CSN complex plays a key role in various cellular pathways: through a metalloprotease activity of its Csn5 deneddylating enzyme, it regulates the activity of Cullin-RING ligases (CRLs). Indeed, Csn5 has been found amplified in many tumors, but, due to its pleiotropic effects, it is difficult to dissect its function and the involvement in cancer progression. Moreover, while growing evidences point to the neddylation function as a good target for drug development; specific inhibitors have not yet been developed for the CSN. Here, we propose the yeast Saccharomyces cerevisiae as a model system to screen libraries of small molecules as inhibitors of cullins deneddylation, taking advantage of the unique feature of this organism to survive without a functional CSN5 gene and to accumulate a fully neddylated cullin substrate. By combining molecular modeling and simple genetic tools, we were able to identify two small molecular fragments as selective inhibitors of Csn5 deneddylation function
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
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