1,721,009 research outputs found
Density Peak clustering of protein sequences associated to a Pfam clan reveals clear similarities and interesting differences with respect to manual family annotation
No full textBackground: The identification of protein families is of outstanding practical importance for in silico protein annotation and is at the basis of several bioinformatic resources. Pfam is possibly the most well known protein family database, built in many years of work by domain experts with extensive use of manual curation. This approach is generally very accurate, but it is quite time consuming and it may suffer from a bias generated from the hand-curation itself, which is often guided by the available experimental evidence. Results: We introduce a procedure that aims to identify automatically putative protein families. The procedure is based on Density Peak Clustering and uses as input only local pairwise alignments between protein sequences. In the experiment we present here, we ran the algorithm on about 4000 full-length proteins with at least one domain classified by Pfam as belonging to the Pseudouridine synthase and Archaeosine transglycosylase (PUA) clan. We obtained 71 automatically-generated sequence clusters with at least 100 members. While our clusters were largely consistent with the Pfam classification, showing good overlap with either single or multi-domain Pfam family architectures, we also observed some inconsistencies. The latter were inspected using structural and sequence based evidence, which suggested that the automatic classification captured evolutionary signals reflecting non-trivial features of protein family architectures. Based on this analysis we identified a putative novel pre-PUA domain as well as alternative boundaries for a few PUA or PUA-associated families. As a first indication that our approach was unlikely to be clan-specific, we performed the same analysis on the P53 clan, obtaining comparable results. Conclusions: The clustering procedure described in this work takes advantage of the information contained in a large set of pairwise alignments and successfully identifies a set of putative families and family architectures in an unsupervised manner. Comparison with the Pfam classification highlights significant overlap and points to interesting differences, suggesting that our new algorithm could have potential in applications related to automatic protein classification. Testing this hypothesis, however, will require further experiments on large and diverse sequence datasets
Molecular modeling studies on CNG channel from bovine retinal rod: a structural model of the cyclic nucleotide-binding domain
No full textMovement of the C-Helix during the Gating of Cyclic Nucleotide-Gated Channels
No full textAbstractMovements within the cyclic nucleotide-binding domain of cyclic nucleotide-gated channels are thought to underlie the initial phase of channel gating (Tibbs, G. R., D. T. Liu, B. G. Leypold, and S. A. Siegelbaum. 1998. J. Biol. Chem. 273:4497–4505; Zong, X., H. Zucker, F. Hofmann, and M. Biel. 1998. EMBO J. 17:353–362; Matulef, K., G. E. Flynn, and W. N. Zagotta. 1999. Neuron. 24:443–452; Paoletti, P., E. C. Young, and S. A. Siegelbaum. 1999. J. Gen. Physiol. 113:17–33; Johnson, J. P., and W. N. Zagotta. 2001. Nature. 412:917–921). To investigate these movements, cysteine mutation was performed on each of the 28 residues (Leu-583 to Asn-610), which span the agonist-binding domain of the α-subunit of the bovine rod cyclic nucleotide-gated channel. The effects of Cd2+ ions, 2-trimethylammonioethylmethane thiosulfonate (MTSET) and copper phenanthroline (CuP) on channel activity were examined, in excised inside-out patches in the presence and in the absence of a saturating concentration of cGMP. The application of 100μM Cd2+ in the presence of saturating concentration of cGMP caused an irreversible and almost complete reduction of the current in mutant channels E594C, I600C, and L601C. In the absence of cGMP, the presence of 100μM Cd2+ caused a strong current reduction in all cysteine mutants from Asp-588 to Leu-607, with the exception of mutant channels A589C, M592C, M602C, K603C, and L606C. The selective effect of Cd2+ ions was very similar to that observed when adding the oxidizing agent CuP to the bath medium, except for mutant channel G597C, where CuP caused a stronger current decrease (67±7%) than Cd2+ (23±4%). In the absence of cGMP, MTSET caused a reduction of the current by >40% in mutant channels L607C, L601C, I600C, G597C, and E594C, whereas in the presence of cGMP only mutant channel L601C was affected. The application of MTSET protected many mutant channels from the effects of Cd2+ and CuP. These results suggest that, when CNG channels are in the open state, residues from Asp-588 to Leu-607 are in an α-helical structure, homologous to the C-helix of the catabolite gene activator protein (Weber, I. T., and T. A. Steitz. 1987. J. Mol. Biol. 198:311–326). Furthermore, residues Glu-594, Gly-597, Ile-600, and Leu-601 of these helices belonging to two different subunits must be in close proximity. In the closed state the C-helices are in a different configuration and undergo significant fluctuations
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
Un sogno per l'imperatore. La teoria politica del De ortu et fine Romani imperii di Engelbert di Admont
No full textL'articolo sostiene che, a dispetto della carriera di Engelbert di Admont come monaco e abate benedettino attivo in un'area marginale dell'Impero, il suo De ortu et fine Romani Imperii può essere considerato una fonte importante per il linguaggio politoco e per le idee politiche dei sostenitori dell'Impero durante il regno di Enrico VII. L'autore mostra come Engelbert, adottando uno stile scolastico standard, argomenti a favore dell'Impero, fondandosi sia sulla Politica di Aristotele sia sul De civitate dei di Agostino. Engelbert è inoltre a conoscenza di speculazioni escatologiche che pongono in connessione la dissoluzione dell'Impero e l'avvento dell'Anticristo. Radicate nella tradizione dell'ideoalogia imperiale, le tesi dell'abate della Stiria convergono con le idee espresse nei documenti ufficiali di Enrico VI
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
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