1,721,549 research outputs found
Small-Molecule-Induced Soluble Oligomers of α-Synuclein with Helical Structure
Full text linkAccumulation of α-synuclein (αSyn) aggregates constitutes the hallmark of synucleinopathies including Parkinson's disease. However, many steps from the innocuous, monomeric αSyn toward misfolded oligomers and fibrillar species remain unclear. Here, we show that αSyn can form in solution α-helical oligomers, which are off-pathway to fibrillization, through interaction with the tetrapyrrole phthalocyanine tetrasulfonate. Chemical cross-linking combined with mass spectrometry reveals a large number of intermolecular cross-links along the entire αSyn sequence in the phthalocyanine tetrasulfonate-stabilized αSyn oligomers. Our study suggests that stabilization of structured oligomers by small molecules provides a viable strategy to interfere with αSyn fibrillization.Fil: Fonseca Ornelas, Luis. Max Planck Institute for Biophysical Chemistry; AlemaniaFil: Schmidt, Carla. Martin Luther University Halle-Wittenberg; AlemaniaFil: Camacho Zarco, Aldo R.. German Center for Neurodegenerative Diseases ; AlemaniaFil: Fernandez, Claudio Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario. Universidad Nacional de Rosario. Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario; Argentina. Max Planck Institute for Biophysical Chemistry; AlemaniaFil: Becker, Stefan. Max Planck Institute for Biophysical Chemistry; AlemaniaFil: Zweckstetter, Markus. Max Planck Institute for Biophysical Chemistry; Alemania. German Center for Neurodegenerative Diseases ; Alemania. Universität Göttingen; Alemani
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
Small molecule-mediated stabilization of vesicle-associated helical Alpha-synuclein inhibits patogenic misfolding and aggregation
Full text linkα-synuclein is an abundant presynaptic protein that is important for regulation of synaptic vesicle trafficking, and whose misfolding plays a key role in Parkinson’s disease. While α-synuclein is disordered in solution, it folds into a helical conformation when bound to synaptic vesicles. Stabilization of helical, folded α-synuclein might therefore interfere with α-synuclein-induced neurotoxicity. Here we show that several small molecules, which delay aggregation of α-synuclein in solution, including the Parkinson’s disease drug selegiline, fail to interfere with misfolding of vesicle-bound α-synuclein. In contrast, the porphyrin phtalocyanine tetrasulfonate directly binds to vesicle-bound α-synuclein, stabilizes its helical conformation and thereby delays pathogenic misfolding and aggregation. Our study suggests that small-molecule-mediated stabilization of helical vesicle-bound α-synuclein opens new possibilities to target Parkinson’s disease and related synucleinopathiesFil: Fonseca Ornelas, Luis. Max Planck Institute for Biophysical Chemistry; AlemaniaFil: Eisbach, Sybille E.. University Medicine; AlemaniaFil: Paulat, Maria. Max Planck Institute for Biophysical Chemistry; AlemaniaFil: Giller, Karin. Max Planck Institute for Biophysical Chemistry; AlemaniaFil: Fernandez, Claudio Oscar. Universidad Nacional de Rosario; Argentina. Instituto de Investigaciones para el Descubrimiento de Farmacos de Rosario; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Outeiro, Tiago F. University Medicine; Alemania. University Medical Center; AlemaniaFil: Becker, Stefan. Max Planck Institute for Biophysical Chemistry; AlemaniaFil: Zweckstetter, Markus. Max Planck Institute for Biophysical Chemistry; Alemania. University Medical Center; Alemania. German Center for Neurodegenerative Diseases; Alemani
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
Structure of the RBD-PRDI fragment of the antiterminator protein GlcT
No full textGlcT is a transcriptional antiterminator protein that is involved in regulation of glucose metabolism in Bacillus subtilis. Antiterminator proteins bind specific RNA sequences, thus preventing the formation of overlapping terminator stem-loops. The structure of a fragment (residues 3-170) comprising the RNA-binding domain (RBD) and the first regulatory domain (PRDI) of GlcT was solved at 2.0 angstrom resolution with one molecule in the asymmetric unit. The two domains are connected by a helical linker. Their interface is mostly constituted by hydrophobic interactions.Max Planck Societ
Extending the detectable time window of fast protein dynamics using 1HN E-CPMG
No full textAbstract Recent advances in high power NMR relaxation dispersion experiments have significantly enhanced our ability to study fast µs timescale motions in proteins, which are crucial for understanding their biological functions. Here, we have extended the detectable time window of such fast dynamics with the development of e xtreme power 1 H C arr- P urcell- M eiboom- G ill ( 1 H E-CPMG) experiments targeted at the backbone amide protons ( 1 H N ). Using this methodology, artifact-free relaxation dispersion profiles can be obtained up to extreme pulsing conditions with minimal setup effort using commonly used standard NMR hardware. We demonstrate the utility of ¹H E-CPMG on human ubiquitin, revealing that the previously reported peptide flip motion influences a larger region of the protein backbone than previously recognized. Additionally, we directly observed a faster dynamic process at residue T09, aligning with previously predicted pincer mode motion. These findings underscore the effectiveness of 1 H E-CPMG in extending the temporal resolution at which biologically relevant fast protein dynamics can be studied
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
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