1,720,953 research outputs found

    Site-directed mutagenesis of charged amino acid residues on the CpxASD and CpxP in E. coli, potentially important for signaling and direct interaction

    Full text link
    Bacterial pathogens must endure diverse environmental stresses that they encounter while colonizing and infecting a host. Two-component signal transduction systems (TCSTs) are the most widespread regulatory systems in bacteria, but importantly absent in mammals. In general, TCSTs sense and interpret stimuli, then use such information to respond by modulating the repertoire of genes expressed, allowing to ultimately mediate adaptations for survival. The CpxRA TCST envelope stress response (ESR) system in Escherichia coli and other Gram-negatives has been linked to virulence factors, antibiotic resistance and envelope stress. The CpxRA system is made up of the sensor histidine kinase (HK) CpxA, the cytosolic response regulator (RR) CpxR, and the periplasmic accessory inhibitor CpxP. In the absence of inducers, the periplasmic sensor domain of CpxA has been proposed to interact with CpxP, inhibiting CpxA autokinase activity and causing it to act as a phosphatase for CpxR~P dephosphorylation, maintaining the pathway in an off state. Intriguingly, the mechanism by which CpxA detects and transduces signals, as well as the one allowing for it to directly interact with CpxP, are still not completely understood. In the present study, I sought to determine whether some of the recently identified surface-exposed amino acid residues comprising large negatively charged patches in the CpxASD of E. coli are important for pathway activation and partner interaction (specifically with CpxP). Experimental analyses were performed by following a site-directed specific mutational approach, based on structural and electrostatic analysis of the CpxASD. The effects of cpxA lysine and alanine mutations were analyzed by transforming them into a ΔcpxA E. coli strain. Such strains were grown in either acid, neutral or alkaline pH, or in the presence of nlpE or cpxP overexpression. Cpx activity levels were then determined using a Cpx-regulated lacZ reporter gene (cpxP'-lacZ+) to indirectly measure pathway activation through β-galactosidase assays. The cpxA strains harboring the E91K, D113K or E91K+D113K mutated alleles displayed constitutive pathway hyperactivation activities and lost sensitivity toward overproduction of CpxP and NlpE. Protein levels however did not seem to be affected by the introduced mutations. I also investigated the potential for specific positively charged residues in CpxP to be direct interaction points of the previosuly characterized negatively charged residues in CpxASD, using complementary charge mutations. I determined that a specific direct-contact site could be located between the D113 negatively charged amino acid residue in the CpxASD and the R139 positively charged residue in the CpxP concave surface. This represents the first time in which a specific localized interaction site between two amino acid residues of the CpxA and CpxP components has been described. A better understanding and characterization of such interaction could open the path for targeted inhibition of the pathway in the future, leading to alternative therapeutic treatments for diseases such as infectious diarrhea

    Going Beyond Counting First Authors in Author Co-citation Analysis

    Full text link
    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

    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 link
    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

    Dispelling the Myths Behind First-author Citation Counts

    Full text link
    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

    No full text
    Nao informado

    koamabayili/VECTRON-author-checklist: VECTRON author checklist

    No full text
    We have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used

    Author Under Sail The Imagination of Jack London, 1893-1902

    No full text
    In Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Intro -- Title Page -- Copyright Page -- Dedication -- Contents -- Acknowledgments -- Introduction -- 1. Spirit Truth -- 2. From Absorption to Theatricality and Back Again -- 3. "I Will Build a New Present" -- 4. Sons as Authors -- 5. Fathers as Publishers -- 6. The Daughter as Author -- 7. Lovers as Authors -- 8. At Sea with the Family -- 9. Yellow News, Yellow Stories -- 10. The Return Home -- Notes -- Bibliography -- Index -- About Jay WilliamsIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Description based on publisher supplied metadata and other sources.Electronic reproduction. Ann Arbor, Michigan : ProQuest Ebook Central, YYYY. Available via World Wide Web. Access may be limited to ProQuest Ebook Central affiliated libraries
    corecore