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    Escherichia coli RNA fragmenteerimine MazF ning MqsR toksiinide poolt

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    Väitekirja elektrooniline versioon ei sisalda publikatsiooneBakterite elu on täis väljakutseid: nad peavad toime tulema ohtlike kemikaalide, vaenulike naabrite ja toitainete puudusega. Erinevate ohtude vastu võitlemiseks on bakteritel välja arenenud mitmed stressile reageerimise mehhanismid. Bakteriaalsed toksiin-antitoksiin süsteemid on väikesed parasiitsed üksused, millest mõned on rakud suutnud värvata stressivastuse radadesse. Nendelt geneetilised üksustelt toodetakse raku kasvu pärssivat toksilist valku ja seda inaktiveerivat antitoksiini. Kuna antitoksiinid on ebastabiilseid tuleb neid stabiilsete toksiinide kontrolli all hoidmiseks pidevalt juurde toota. Seega, kui moodul peaks kaotsi minema või antitoksiinide tootmine on takistatud, vabanevad toksiinid ning pärsivad rakkude kasvu. Stressivastuses osalevaid toksiine peetakse peamiselt kasvuregulaatoriteks, mis vastusena kahjulikele teguritele vähendavad rakkude metaboolset aktiivsust. Hiljutised uurimused väidavad, et osadel toksiin-antitoksiini süsteemidel on rakus keerukam funktsioon - nad reguleerivad spetsiifiliste geenide avaldumist. Selle kõige silmapaistvamaks näiteks on Escherichia coli endoribonukleaasist toksiin MazF, mis arvatakse erinevate stresside korral ümberprogrammeerivat kogu raku translatsioonilise masinavärgi. Spekuleeritakse, et MazF muudab ribosoomide translatsioonilist eelistust eemaldades 16S rRNA küljest anti-Shine-Dalgarno järjestuse. Sellised ribosoomid arvatakse transleerivat kärbitud 5’ otstega stressiga seotud geenide mRNA-sid, mis on samuti MazFi poolt tekitatud. Me uurisime RNA lõikamist MazFi ja teise endoribonukelasse toksiini, MqsRi, poolt Escherichia colis ning ei näinud mingeid tõendeid, mis toetaks sellist keerukat translatsiooni ümberprogrammeerimise mehhanismi. Me näeme, et MazF ja MqsR käituvad ainult kui kasvupärssijad, mis lõikavad kõike kättesaadavat struktureerimata RNA-d. Traditsiooniliselt peetakse Escherichia coli endoribonukleaasidest toksiine ainult mRNA lagundajateks, kuid meie andmed viitavad sellele, et kasvu pidurdatakse ka läbi prekursor rRNA-de lagundamise.Lives of bacteria are full of perils: they have to cope with dangerous chemicals, hostile neighbours and limited nutrients. To counter various hazards, bacteria have developed many stress response mechanisms. Bacterial toxin-antitoxin systems are small parasitic modules, which have been in some cases also adopted into stress response pathways. These genetic units encode for an autotoxic protein and an antitoxin that neutralizes the toxin. Antitoxins are labile and need to be constantly produced to inhibit the extremely stable toxins. Thus, when the module is lost or antitoxin production gets hindered the toxins become free to inhibit the growth. Toxins involved in stress response are mainly considered to be regulators of growth, which reduce the metabolic activity of cells in response to harmful conditions. Recently, some toxin-antitoxin systems have been reported to have a more sophisticated function: the regulation of specific genes. The most prominent example is the MazF toxin of Escherichia coli, which is an endoribonuclease hypothesized to reprogram the translational machinery during various stresses. It is speculated that MazF removes a piece of the 3’ end from 16S rRNA in mature ribosomes, which results in altered translational specificity. Such modified ribosomes are thought to translate stress-related transcripts with truncated 5’ UTR-s, which are hypothesized to also be generated by MazF. We studied the RNA cleavage by MazF and another endoribonuclease toxin, MqsR, in Escherichia coli and saw no evidence for such elaborate translational reprogramming. Instead, we show that MazF and MqsR act as growth inhibitors, which cleave unstructured RNA. Traditionally, endoribonuclease toxins of Escherichia coli are viewed only as degraders of mRNA, but our data implies that growth arrest is also facilitated through degradation of precursor rRNA.https://www.ester.ee/record=b520943

    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

    Characterisation of Type II toxins discovered through iterative guilt-by-association search

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    The classical toxin-antitoxin (TA) system is encoded as a bicistronic operon consisting of toxin and antitoxin genes. Toxin-antitoxin systems have been studied for more than 30 years and have been shown to play an important role in bacterial immunity and stress response. The most common and best-studied class of TA systems is type II, where both the toxin and the antitoxin are proteins, and the toxin is neutralized by the antitoxin via direct interaction. My thesis helps to uncover the molecular mechanisms of type II toxins found by the bioinformatics tool NetFlax (standing for Network of Flanking genes for toxins and antitoxins) via metabolic labelling assays. I characterize several toxins from different functional domains and show how the toxins affect the bacterial cell using Escherichia coli as the model organism

    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

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