1,721,126 research outputs found
The three-dimensional structure of a type I module from titin: a prototype of intracellular fibronectin type III domains
No full textAbstractBackground: Titin is a huge protein (∼3 MDa) that is present in the contractile unit (sarcomere) of striated muscle and has a key role in muscle assembly and elasticity. Titin is mainly composed of two types of module (type I and II). Type I modules are found exclusively in the region of titin localised in the A band, where they are arranged in a super-repeat pattern that correlates with the ultrastructure of the thick filament. No structure of a titin type I module has been reported so far.Results: We have determined the structure of a representative type I module, A71, using nuclear magnetic resonance (NMR) spectroscopy. The structure has the predicted fibronectin type III fold. Titin-specific conserved residues are either located at the putative module–module interfaces or along one side of the protein surface. Several proline residues that contribute to two stretches in a polyproline II helix conformation are solvent-exposed and line up as a continuous ribbon extending over more than two-thirds of the module surface. Homology models of the type I module N-terminal to A71 (A70) and the double module A70–A71 were used to discuss possible intermodule interactions and their role in module–module orientation.Conclusions: As residues at the module–module interfaces are highly conserved, we speculate that similar interactions govern all of the interfaces between type I modules in titin. This conservation would lead to a regular multiple array of similar surface structures. Such an arrangement would allow arrays of contiguous type I modules to expose multiple proline stretches in a highly regular way and these may act as binding sites for other thick filament proteins
Weighting of experimental evidence in macromolecular structure determination
No full textThe determination of macromolecular structures requires weighting of experimental evidence relative to prior physical information. Although it can critically affect the quality of the calculated structures, experimental data are routinely weighted on an empirical basis. At present, cross-validation is the most rigorous method to determine the best weight. We describe a general method to adaptively weight experimental data in the course of structure calculation. It is further shown that the necessity to define weights for the data can be completely alleviated. We demonstrate the method on a structure calculation from NMR data and find that the resulting structures are optimal in terms of accuracy and structural quality. Our method is devoid of the bias imposed by an empirical choice of the weight and has some advantages over estimating the weight by cross-validation
The three-dimensional structure of a type I module from titin: A prototype of intracellular fibronectin type III domains
No full textBACKGROUND:
Titin is a huge protein ( approximately 3 MDa) that is present in the contractile unit (sarcomere) of striated muscle and has a key role in muscle assembly and elasticity. Titin is mainly composed of two types of module (type I and II). Type I modules are found exclusively in the region of titin localised in the A band, where they are arranged in a super-repeat pattern that correlates with the ultrastructure of the thick filament. No structure of a titin type I module has been reported so far.
RESULTS:
We have determined the structure of a representative type I module, A71, using nuclear magnetic resonance (NMR) spectroscopy. The structure has the predicted fibronectin type III fold. Titin-specific conserved residues are either located at the putative module-module interfaces or along one side of the protein surface. Several proline residues that contribute to two stretches in a polyproline II helix conformation are solvent-exposed and line up as a continuous ribbon extending over more than two-thirds of the module surface. Homology models of the type I module N-terminal to A71 (A70) and the double module A70-A71 were used to discuss possible intermodule interactions and their role in module-module orientation.
CONCLUSIONS:
As residues at the module-module interfaces are highly conserved, we speculate that similar interactions govern all of the interfaces between type I modules in titin. This conservation would lead to a regular multiple array of similar surface structures. Such an arrangement would allow arrays of contiguous type I modules to expose multiple proline stretches in a highly regular way and these may act as binding sites for other thick filament proteins
ISD: A Software Package for Bayesian NMR Structure Calculation
No full textSUMMARY: The conventional approach to calculating biomolecular structures from nuclear magnetic resonance (NMR) data is often viewed as subjective due to its dependence on rules of thumb for deriving geometric constraints and suitable values for theory parameters from noisy experimental data. As a result, it can be difficult to judge the precision of an NMR structure in an objective manner. The Inferential Structure Determination (ISD) framework, which has been introduced recently, addresses this problem by using Bayesian inference to derive a probability distribution that represents both the unknown structure and its uncertainty. It also determines additional unknowns, such as theory parameters, that normally need be chosen empirically. Here we give an overview of the ISD software package, which implements this methodology. AVAILABILITY: The program is available at http://www.bioc.cam.ac.uk/is
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
ARIA: automated NOE assignment and NMR structure calculation.
No full textMOTIVATION: In the light of several ongoing structural genomics projects, faster and more reliable methods for structure calculation from NMR data are in great demand. The major bottleneck in the determination of solution NMR structures is the assignment of NOE peaks (nuclear Overhauser effect). Due to the high complexity of the assignment problem, most NOEs cannot be directly converted into unambiguous inter-proton distance restraints. RESULTS: We present version 1.2 of our program ARIA (Ambiguous Restraints for Iterative Assignment) for automated assignment of NOE data and NMR structure calculation. We summarize recent progress in correcting for spin diffusion with a relaxation matrix approach, representing non-bonded interactions in the force field and refining final structures in explicit solvent. We also discuss book-keeping, data exchange with spectra assignment programs and deposition of the analysed experimental data to the databases. AVAILABILITY: ARIA 1.2 is available from: http://www.pasteur.fr/rec herche/unites/Binfs/aria/. SUPPLEMENTARY INFORMATION: XML DTDs (for chemical shifts and NOE crosspeaks), Python scripts for the conversion of various NMR data formats and the results of example calculations using data from the S. cerevisiae HRDC domain are available from: http://www.pasteur.fr/recherche/unites/Binfs/aria
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
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