1,721,035 research outputs found

    CHK2 kinase in the DNA damage response and beyond

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    The serine/threonine kinase CHK2 is a key component of the DNA damage response. In human cells, following genotoxic stress, CHK2 is activated and phosphorylates more than 20 proteins to induce the appropriate cellular response, which, depending on the extent of damage, the cell type, and other factors, could be cell cycle checkpoint activation, induction of apoptosis or senescence, DNA repair, or tolerance of the damage. Recently, CHK2 has also been found to have cellular functions independent of the presence of nuclear DNA lesions. In particular, CHK2 participates in several molecular processes involved in DNA structure modification and cell cycle progression. In this review, we discuss the activity of CHK2 in response to DNA damage and in the maintenance of the biological functions in unstressed cells. These activities are also considered in relation to a possible role of CHK2 in tumorigenesis and, as a consequence, as a target of cancer therapy

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The 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

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    “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

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    We 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

    Chk2 kinase regulation by Nbs1 and search for Chk2 interacting proteins

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    The mammalian Chk2 protien kinase has a key role in the activation of DNA damaged induced cell cycle checkpoints. After low doses of IR Chk2, activated in an ataxia telangiectasia mutataed (ATM)- dependent manner, can phosphorylate several substartes causing arrest in G1, S and G2-M. Recently we found that the activation of Chk2 by gamma-radiation requires, besides ATM, also Nbs1, the gene product invovled in the Nijmegen Breakage Syndrome (NBS), a disorder that shares with AT a variety of phenotypic defects. In NBS cells, the defective Chk2 phosphoryaltion and kinase activation can be complemented by reintroduction of wild type Nbs1, but neither by a C-terminal deletion mutant of Nbs1 at aa 59, that cannot form a complex with Mre11 and Rad50, nor by a Nbs1 mutated at Ser343, the ATM phosphorylation site. Because in NBS cells Chk2 maintains its nuclear localization, we can exclude a mislocalization as a the cause of its failed activation. Importantly, the failure of NBS cells to stop entry into mitosis after IR be corrected by the reintroduction of a wild type Nbs1, but not by a Ser343 mutant, suggesting that this checkpoint defect may result from the inability to activate Chk2.To find out Chk2 interacting proteins we have undertaken yeast two hybrid screens using the full lenght Chk2 as a bait and two different cDNA libraries. About 250 clones were analyzed, with 5 clones strongly interacting and 12 weakly interacting with Chk2. Some of these encode for cytoplasmic proteins while others for nuclear proteins involved on checkpoint controls, nucleotide metabolism, transcription, translation and degradation. Studies are in progress to determine the in vivo interaction of these cDNA products with Chk2

    The Saccharomyces cerevisiae SDA1 gene is required for actin cytoskeleton organization and cell cycle progression

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    The organization of the actin cytoskeleton is essential for several cellular processes. Here we report the characterization of a Saccharomyces cerevisiae novel gene, SDA1, encoding a highly conserved protein, which is essential for cell viability and is localized in the nucleus. Depletion or inactivation of Sda1 cause cell cycle arrest in G 1 by blocking both budding and DNA replication, without loss of viability. Furthermore, sda1-1 temperature-sensitive mutant cells arrest at the non-permissive temperature mostly without detectable structures of polymerized actin, although a normal actin protein level is maintained, indicating that Sda1 is required for proper organization of the actin cytoskeleton. To our knowledge, this is the first mutation shown to cause such a phenotype. Recovery of Sda1 activity restores proper assembly of actin structures, as well as budding and DNA replication. Furthermore we show that direct actin perturbation, either in sda1-1 or in cdc28-13 cells released from G 1 block, prevents recovery of budding and DNA replication. We also show that the block in G 1 caused by loss of Sda1 function is independent of Swe1. Altogether our results suggest that disruption of F-actin structure can block cell cycle progression in G 1 and that Sda1 is involved in the control of the actin cytoskeleton

    Un GIS per il territorio litoraneo: la Sicilia sud orientale

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    La costa è un ambiente complesso in cui interagiscono diversi argomenti, per la cui documentazione archeologica la gestione dei dati topografici e cartografici trova una sede naturale nelle piattaforme software dei sistemi informativi ‘geografici e territoriali’. Com’è noto, infatti, in molti ambiti archeologici, e negli studi su scala territoriale in particolare, i sistemi GIS possono essere non solo uno strumento atto ad acquisire, gestire e visualizzare dati topografici, ma anche ad integrare e analizzare dati alfanumerici e grafici, mediante un approccio multiscalare. L’acronimo GIS, ossia Geographic Information System, può considerarsi l’equivalente anglosassone dell’italiano SIT, vale a dire Sistema Informativo Territoriale. Con tale terminologia (GIS) si vuole indicare in questa sede un sistema digitale in grado di associare dei dati topografici e archeologici alla loro posizione geografica sulla superficie terrestre e di elaborarli per estrarne informazioni: la maggiore potenzialità della tecnologia GIS è, infatti, la capacità di integrazione in un unico ambiente digitale le operazioni legate all'uso di database con l'analisi geografica consentita dalle cartografie numeriche, sia raster che vettoriali, attraverso interrogazioni. Proprio per tale ragione si fa ricorso nella sua definizione al termine sistema, in quanto tale risorsa non va considerata come mero strumento o software specifico, ma come un insieme composto da varie entità, indipendenti ma tra loro interconnesse: la piattaforma di software cartografico e una la base informativa. Peraltro, il sistema è definito informativo proprio perché in grado di gestire, elaborare e implementare informazioni di vario genere, se ovviamente adeguatamente organizzate in archivi (dataset): attraverso l’aiuto di un calcolatore (il computer), il GIS è, infatti, in grado di gestire le relazioni che possono sussistere tra grandi quantità di dati e condurre analisi complesse (cartografiche, statistiche, etc.). Si tratta, quindi, di un sistema complesso, fatto di entità e relazioni, la cui struttura viene definita e calibrata in base alle caratteristiche del caso studio e che prescinde dal supporto informatico, il quale va inteso solamente come strumento che agevola una gestione più veloce e precisa. La base informativa del sistema informativo geografico (GIS) che si presenta consiste nella digitalizzazione di dati scaturiti da ricerche condotte nell’ultimo ventennio sulla costa sud orientale della Sicilia, i cui risultati sono raccolti in questo volume. Il catalogo delle unità topografiche (UT), in appendice, è costituito da 116 schede, che rappresentano altrettante aree o punti di produzione, antichi e moderni, censiti nel corso delle ricognizioni sul litorale e in indagini coordinate nell’ambito delle fonti cartografiche storiche: sono qui riportate in formato tabellare le relative schede topografiche, ordinate e numerate seguendo un ordine da Nord a Sud. Oltre al toponimo, al comune di pertinenza, alla posizione, di ogni UT è data una breve indicazione della categoria di pertinenza nell’ambito delle produzioni litoranee

    Dispelling the Myths Behind First-author Citation Counts

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    We 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

    Author Index

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