1,720,973 research outputs found
A possible molecular mechanism for parasitic inhibition by lactoferrin
No full textTransferrins (Tfs) belong to a family of iron-binding glycoproteins
possessing similar aminoacid sequence though they have different
biological functions and locations. Lactoferrin (Lf) is expressed and
secreted from glandular epithelial cells and from mature neutrophiles of
mammalian and it is an important component of the aspecific host defence
or natural immunity, including resistance to parasitic infections. Serum
transferrin (sTf) is synthesized by the liver of mammals and secreted into
the blood stream; its primary function is iron transport. Ovotransferrin
(Otrf), synthesized by avians, displays both iron transport and protective
functions.
Parasites synthesize papain-like cysteine proteases that are relevant
for the virulence and pathogenicity of parasites, being involved in several
aspects of the parasite life cycle, it is therefore possible that the antiparasitic
activity of Lf could be due to the inhibition of parasitic papain-like cysteine
protease that we have recently observed.
In this study we have investigated the thermodynamic parameters
of hLf, bLf and Otrf inhibition of the parasitic papain-like type I cysteine
proteases from Leishmania infantum, Trypanosoma cruzi and Trypanosoma
brucei. bLf, hLf and Otrf, both in the apo- and olo-forms, showed time- and
concentration-dependent inhibition of the catalytic activity of papain and of
type I proteases from L.infantum, T. cruzi and T. brucei. The KI values
observed for bLf and hLf inhibition of L. infantum, T. cruzi and T. brucei
proteases were in the nanomolar range (KI = 3.1 nM), lower than KI values
observed for papain inhibition (KI = 24 nM). Otrf showed lower inhibition
of cysteine proteases (KI = 0.6 µM). On the contrary, sTf did not display any
inhibition towards parasitic proteases, according to its different role in
mammals. The inhibition of parasitic cysteine proteases by hLf, bLf and
Otrf appeared to conform to a competitive mechanism. The observed pH
optimum for bLf inhibition of parasitic proteases was around neutrality,
while it was acidic for hLf and alkaline for Otrf. The further quantitative
analysis of pH dependence of the intrinsic ligand-independent inhibition
constant KI allowed the evaluation of pKa values that define the acid-base
equilibrium of amino acidic residue(s) modulating the enzyme(s)-inhibitor
recognition events. SDS-PAGE showed that hLf, bLf and Otrf were easily
degraded by either papain or parasitic type I protease during the assay
incubation time (few minutes) and it is likely that one or more protease
inhibitory peptides were generated from protein hydrolysis.
As a matter of fact, a sequence present near the C-terminus of
human (hLf) and bovine (bLf) lactoferrin shows homology with the
sequence of the active site of cystatins, which are competitive inhibitors of
papain-like cysteine proteases. The same sequence is present, though with
lower homology, in Otrf and, with even lower homology, in sTf.
Therefore, we have charactherized by MALDI-TOF the profile of
Lf cleavage by papain and preliminary data suggest the presence of a
cystatin-like peptide in two proteolytic fragments of hLf and in one
proteolytic fragment of bLf.Le transferrine (Tfs) sono una famiglia di glicoproteine in grado di
legare reversibilmente il ferro, e presentano un’elevata omologia di
sequenza tra tutti i membri di questa famiglia. In particolare la lattoferrina
(Lf) è prodotta e secreta nelle cellule ghiandolari epiteliali ed è presente nei
granuli dei granulociti neutrofili dei mammiferi. Essa rappresenta
un’importante componente della difesa immunitaria aspecifica dell’ospite.
La siero transferrina (sTf) invece è sintetizzata nel fegato, ed è coinvolta
unicamente nel trasporto del ferro. L’ovotransferrina (Otrf), l’omologa
aviaria della Lf , svolge sia una funzione di difesa che di trasporto del ferro.
Le proteasi a cisteina papaina-simili da protozoi e metazoi
parassiti, secretorie e di membrana, partecipano ai processi di morfogenesi
degli organismi patogeni, sono implicate nell’invasione delle cellule e dei
tessuti da parte dei parassiti, riducono la risposta immunitaria dell’ospite e
costituiscono uno dei fattori più rilevanti nelle patologie associate alle
infestazioni da parassiti. Pertanto, a fronte della capacità della Lf di
svolgere un’azione antiparassitaria, noi abbiamo ipotizzato che la Lf possa
svolgere tale azione grazie all’inattivazione delle suddette proteasi a
cisteina.
Nel presente lavoro abbiamo studiato le proprietà termodinamiche
dell’inibizione delle proteasi a cisteina di alcuni parassiti, quali Leishmania
infantum, Tripanosoma cruzi e Trypanosoma brucei. Tale studio è stato
esteso anche verso la papaina, capostipite di questa famiglia. Innanzitutto è
emerso una maggiore affinità delle transferrine studiate (bLf, hLf e Otrf, in
forma apo e olo) verso le proteasi parassitarie (KI = 3.1 nM) rispetto a
quella verso la papaina (KI = 24 nM). Otrf risulta essere l’inibitore con
minore affinità (KI = 0.6 µM). Inoltre è emerso che la sTf non è in grado di
svolgere un’azione inibitoria, coerentemente con la sua funzione nei
mammiferi. L’inibizione di tutte le proteasi risulta essere conforme ad un
meccanismo di inibizione competitivo.
Da un’analisi della dipendenza del pH dei suddetti fenomeni di
inibizione si è osservato una maggiore attività della bLf a pH fisiologico
mentre la hLf inibisce più efficacemente a valori di pH acidi (pH = 5.0) e la
Otrf a valori di pH alcalini (pH = 9.0). La dipendenza dal pH del parametro
KI relativo all’interazione degli inibitori studiati con gli enzimi, ha permesso
di evidenziare la variazione di diversi valori di pKa, ascrivibili ad eventi di
protonazione e deprotonazione di differenti gruppi ionizzabili.
Inoltre si è osservato, a seguito di SDS-page, una parziale idrolisi
della Lf e della Otrf durante diverse incubazioni con la papaina e con le
proteasi parassitarie, e l’insieme di tali dati suggerisce la liberazione di un
peptide, che può quindi inibire competitivamente le suddette proteasi a
cisteina.
A supporto di tale ipotesi, si è osservato in presenza della porzione
C-terminale della Lf, una sequenza aminoacidica che presenta un’elevata
omologia con il sito attivo delle cistatine, una (super)famiglia di proteina,
riconosciute essere gli inibitori reversibili per eccellenza delle proteasi a
cisteina papaina-simili. Abbiamo quindi caratterizzato, mediante MALDI
TOF, il profilo di idrolisi della Lf ad opera della papaina, ed è stata
riscontrata la presenza di frammenti contenenti tale sequenza cistatinosimile, sia nella bLf che nell’hLf
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
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
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe 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-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
Author Under Sail The Imagination of Jack London, 1893-1902
No full textIn 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
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