1,721,098 research outputs found
The phytotoxin fusicoccin: a regulator of multiple 14-3-3 targets
No full textL’identificazione della fusicoccina come metabolita responsabile degli effetti tossici di Phomopsis amygdali, dovuti alla sua capacità di attivare irreversibilmente l’H+-ATPasi di plasmalemma, ha dato impulso al chiarimento del meccanismo molecolare di azione della tossina. L’H+-ATPasi di plasmalemma è, ad oggi, l’unico bersaglio dell’azione della FC individuato. La mancata identificazione di siti di legame per la FC in batteri, lieviti, funghi e animali ha fatto ritenere che l’azione della tossina fosse quindi ristretta al regno vegetale. In questo lavoro è dimostrata la capacità della fitotossina di influenzare il processo di aggregazione piastrinica. In particolare, da un’analisi, condotta nel nostro laboratorio è stata identificato il recettore piastrinico GPIb-IX-V come possibile bersaglio dell’azione della fusicoccina. Infatti, la tossina è in grado di promuovere il legame delle proteine regolatrici 14-3-3 alla glicoproteina Ibα e di inibire l’associazione con la subunità Ibβ. Da ciò ne risulta la stimolazione dell’adesione piastrinica al fattore di von Willebrand che determina la diffusione piastrinica e l’attivazione delle integrine αIIbβ3. Tali risultati incoraggiano il proseguimento degli studi volti a stabilire se la fusicoccina possa essere utilizzata nella terapia o nella diagnosi di patologie associate alla coagulazione del sangue. Inoltre, questo lavoro pone le basi ad una futura ricerca volta a determinare la possibile applicazione della tossina ad altri complessi 14-3-3/target.
Inoltre, la disponibilità di un gran numero di derivati e analoghi della fusicoccina ha reso possibile un’analisi dettagliata della correlazione tra attività e struttura chimica. A tale scopo, è stata saggiata l’attività di questi composti correlati alla fusicoccina in saggi sia in vivo che in vitro.The fungal toxin fusicoccin induces plant wilting by affecting ion transport across the plasma membrane of plant cell. The activity of this toxin is so far unknown in humans. In this work, we show that fusicoccin is able to affect the platelet aggregation process.
The toxin associates to platelet intracellular binding sites and induces aggregation in platelet-rich plasma in a dose-dependent manner. We identified the adhesion receptor glycoprotein Ib-IX-V as fusicoccin target. The toxin promotes the binding of the regulatory 14-3-3 proteins to glycoprotein Ibα and hampers that to glycoprotein Ibβ subunit. As a result, platelet adhesion to von Willebrand Factor is stimulated, leading to platelet spreading and integrin αIIbβ3 activation.
We anticipate our study to be a starting point for future therapeutic use of fusicoccin in genetic bleeding diseases characterized by qualitative or quantitative abnormalities of the platelet membrane adhesion receptors. Furthermore, we demonstrated that fusicoccin action can be widen also to other 14-3-3 clients, provided that a mode III motif with an appropriate C terminal amino acid is present. Results obtained suggest also the rationale for fusicoccin inability to promote 14-3-3 binding to targets with a mode I consensus sequence.
In addition, the availability of a large number of fusicoccin derivatives and analogues made possible a detailed analysis of the relationship between activity and chemical structure. The activity of these fusicoccin-related compounds has been tested either in vivo and in vitro
From plant to human physiology: role of the phytotoxin fusicoccin in the platelet aggregation process
No full text
Fungal phytotoxin fusicoccin for the treatmant and diagnosis of coagulation-correlated pathologies.
No full textFusicoccin is a fungal phytotoxin known to induce a strong and permanent activation of the plant plasma membrane H+-ATPase. Fusicoccin promotes the association of 14-3-3 proteins to a mode III binding motif located at the C-terminal end of the enzyme.
Here we show that fusicoccin can stimulate binding of 14-3-3 proteins to the platelet protein Glycoprotein Ib, which also contains a mode III 14-3-3 binding sequence. Glycoprotein Ib is the platelet receptor for von Willebrand Factor and it is essential in the first step of the coagulation process. Fusicoccin binding promotes activation of Glycoprotein Ib and consequent adhesion of platelets to von Willebrand Factor, therefore triggering the aggregation process. Our data propose fusicoccin as a novel compound able to induce platelet aggregation. Therapeutic implications of this finding are also discussed
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
Binding of phosphatidic acid to 14-3-3 proteins hampers their ability to activate the plant plasma membrane H(+) -ATPase
No full textPhosphatidic acid is a phospholipid second messenger implicated in various cellular processes in eukaryotes. In plants, production of phosphatidic acid is triggered in response to a number of biotic and abiotic stresses. Here, we show that phosphatidic acid binds to 14-3-3 proteins, a family of regulatory proteins which bind client proteins in a phosphorylation-dependent manner. Binding of phosphatidic acid involves the same 14-3-3 region engaged in protein target binding. Consequently, micromolar phosphatidic acid concentrations significantly hamper the interaction of 14-3-3 proteins with the plasma membrane H(+) -ATPase, a well characterized plant 14-3-3 target, thus inhibiting the phosphohydrolitic enzyme activity. Moreover, the proton pump is inhibited when endogenous PA production is triggered by phospholipase D and the G protein agonist mastoparan-7. Hence, our data propose a possible mechanism involving PA that regulates 14-3-3-mediated cellular processes in response to stress. © 2012 IUBMB IUBMB Life, 2012
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
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