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Mechanism of membrane perturbation by the antibiotic peptide trichogin GA IV: a physico-chemical study on fluorescent analogs = Il meccanismo di azione del peptide antibiotico Tricogina GA IV: studi chimico-fisici su analoghi fluorescenti
No full text“Il meccanismo di azione del peptide antibiotico Tricogina GA IV: studi chimico-fisici su analoghi fluorescenti” dr. Claudia Mazzuca
La Tricogina GA IV è il componente principale della famiglia dei lipopeptaibolici, un’importante classe di peptidi lineari, che agiscono perturbando il doppio strato lipidico. La sua sequenza è::
Oct-Aib-Gly-Leu-Aib-Gly-Gly-Leu-Aib-Gly-Ile-Lol dove Oct è il gruppo n-octanoile e Lol il leucinolo.
Questo peptide risulta essere estremamente attivo nei confronti di batteri ed eritrociti; tuttavia, i dettagli del suo meccanismo d’azione non sono ancora stati chiariti.
Al fine di studiare in dettaglio il comportamento della tricogina attraverso l’impiego della spettroscopia di fluorescenza (tecnica particolarmente sensibile), sono stati sintetizzati due analoghi – chiamati A3 ed F10 – contenenti le sonde fluorescenti azulene e fluorene rispettivamente in posizione 3 e 10 della catena.
Per stabilire quale sia, tra i tre possibili (formazione di canali, trasportatore di ioni o micellizzazione), il meccanismo d’azione del peptide, sono stati confrontati i risultati di diversi esperimenti indipendenti. In particolare, misure di luce diffusa e di rilascio di sonde di differenti dimensioni dai liposomi hanno permesso di escludere la micellizzazione. Questo risultato è stato anche confermato da esperimenti di microscopia ottica su liposomi giganti. Inoltre, è stato possibile escludere anche che il peptide agisca da trasportatore di ioni, sulla base di misure di rilascio effettuate su membrane a differente viscosità.
Scendendo più in dettaglio a livello molecolare, esperimenti di fluorescenza risolta in tempo hanno mostrano la presenza di un equilibrio monomero-aggregato non solo in acqua, ma anche in membrana: è stato quindi possibile determinare sia le popolazioni relative delle quattro specie che le costanti che regolano gli equilibri tra esse. È stato inoltre possibile dimostrare che solamente gli aggregati in fase lipidica sono responsabili della permeabilizzazione della membrana.
Esperimenti di smorzamento di fluorescenza da parte di lipidi marcati con il gruppo dossile in differenti posizioni lungo la catena hanno mostrato che il peptide è inserito all’interno della membrana: per valori di concentrazione peptidica ai quali non si ha attività, sia l’azulene di A3 che il fluorene di F10 sono posizionati a circa 10 Å dal centro del doppio strato. Tuttavia, quando la concentrazione peptidica raggiunge valori sufficienti ad avere attività, lo smorzamento causato dai dossili posizionati vicino al centro del doppio strato aumenta significativamente, indicando un cambiamento nella topologia del peptide. Si è osservata una stretta correlazione tra la frazione di peptide profondamente inserito in membrana e la frazione di aggregati.
Si può quindi concludere che l’aumento della concentrazione peptidica provoca una transizione a due stati da una forma monomerica inattiva, localizzata sulla superficie della membrana ad una forma aggregata, inserita all’interno del doppio strato, la quale, formando canali, è responsabile della permeabilizzazione e dell’attività biologica.“Mechanism of membrane perturbation by the antibiotic peptide Trichogin GAIV: a physico-chemical study on fluorescent analogs” dr. Claudia Mazzuca
Trichogin GA IV is the main component of the lipopeptaibol family, an important class of antibiotic linear peptides, which exert their action by perturbing the permeability of cell membranes, without interacting with any specific receptor. Trichogin sequence is characterized by an N-terminal fatty acyl group, a C-terminal 1,2-amino alcohol and a high proportion of Aib residues: Oct-Aib-Gly-Leu-Aib-Gly-Gly-Leu-Aib-Gly-Ile-Lol where Oct is n-octanoyl and Lol is leucinol.
This peptide displays a remarkable antibacterial and hemolytic activity, but the details of its mode of action are still unsettled. In order to characterize the behavior of trichogin, we decided to take advantage of the high sensibility of fluorescence spectroscopy: therefore, two trichogin analogues marked with fluorescent probes (fluorene and azulene) were synthesized:
Oct-Aib-Gly-Aal-Aib-Gly-Gly-Leu-Aib-Gly-Dab(Boc)-Leu-OMe (A3)
Oct-Aib-Gly-Leu-Aib-Gly-Gly-Leu-Aib-Gly-Dab(Fmc)-Leu-OMe (F10)
where Aal denotes b-(1-azulenyl)-L-alanine and Fmc the fluorenyl-9-methylcarbonyl group. These analogs display structural and functional properties comparable to those of the parent peptide.
To clarify the mechanism of action (pore formation, ion carrier or detergent- like mechanisms), we compared the outcomes of several independent experiments. Release measurements of markers of different size from liposomes, and scattering measurements allowed us to rule out micellization as the trichogin mechanism of membrane perturbation. These results were confirmed by optical microscopy experiments performed on giant unilamellar vesicles. On the other hand, an ion-carrier mode of action was also excluded, based on peptide-induced leakage experiments using liposomes with membranes of different viscosities. Indeed, voltage-dependent measurements on BLMs confirm that trichogin acts by forming channels of well-defined size.
The molecular details about trichogin mode of action were first investigated performing time-resolved fluorescence experiments. These measurements demonstrate that in water trichogin analogs have a strong tendency to self-associate. A monomer-aggregate equilibrium is found also in the membrane phase. The relative population of the four species present in a water-membrane system, and the constants regulating the equilibria among them were determined. Interestingly, we found that while aggregates are present both in solution and in the lipid phase, membrane leakage is due to peptide oligomers only.
Fluorescence quenching experiments were then performed with water-soluble quenchers (iodide and acrilamide) and with lipids labeled with the doxyl quencher at different positions along the chain. These data show that trichogin is inserted in the lipid phase: at peptide concentration values where no membrane leakage is observed, both the azulene of A3 and the fluorene of F10 are positioned at about 10 Å from the bilayer center. However, as peptide concentration reaches values able to induce liposome leakage, the quenching caused by doxyls located near the center of the bilayer increases markedly, indicating a change in peptide topology. A strict correlation between the fraction of peptide deeply inserted in the membrane and the fraction of trichogin aggregates was found.
Therefore, we can conclude that the increase in peptide concentration brings about a two-state transition from a monomeric, surface-bound and inactive peptide to a buried, aggregated state, forming channels responsible for membrane leakage and bioactivity
Grounded Cognition, Linguistic Relativity, and Abstract Concepts
No full text: Kemmerer's paper convincingly claims that the grounded cognition model (GCM) entails linguistic relativity. Here, we underline that tackling linguistic relativity and cultural differences is vital for GCM. First, it allows GCM to focus more on flexible rather than stable aspects of cognition. Second, it highlights the centrality of linguistic experience for human cognition. While GCM-inspired research underscored the similarity between linguistic and nonlinguistic concepts, it is now paramount to understand when and how language(s) influence knowledge. To this aim, we argue that linguistic variation might be particularly relevant for more abstract concepts-which are more debatable and open to revisions
Overusing the pacifier during infancy sets a footprint on abstract words processing
No full textPerturbations to the speech articulators induced by frequently using an interfering object during infancy (i.e., pacifier) might shape children's language experience and the building of conceptual representations. Seventy-one
typically developing third graders performed a semantic categorization task with abstract, concrete and emotional words. Children who used the pacifier for a more extended period were slower than the others. Moreover, overusing the pacifier increased response time of abstract words, whereas emotional and (above all) concrete words were less affected. Results support the view that abstract words are grounded both in perception-action and in linguistic experience
Exposing implicit biases and stereotypes in human and artificial intelligence: state of the art and challenges with a focus on gender
Full text linkBiases in cognition are ubiquitous. Social psychologists suggested biases and stereotypes serve a multifarious set of cognitive goals, while at the same time stressing their potential harmfulness. Recently, biases and stereotypes became the purview of heated debates in the machine learning community too. Researchers and developers are becoming increasingly aware of the fact that some biases, like gender and race biases, are entrenched in the algorithms some AI applications rely upon. Here, taking into account several existing approaches that address the problem of implicit biases and stereotypes, we propose that a strategy to cope with this phenomenon is to unmask those found in AI systems by understanding their cognitive dimension, rather than simply trying to correct algorithms. To this extent, we present a discussion bridging together findings from cognitive science and insights from machine learning that can be integrated in a state-of-the-art semantic network. Remarkably, this resource can be of assistance to scholars (e.g., cognitive and computer scientists) while at the same time contributing to refine AI regulations affecting social life. We show how only through a thorough understanding of the cognitive processes leading to biases, and through an interdisciplinary effort, we can make the best of AI technology
The TECo Database: Insights on The Semantic Organization of The Ecological Domain.
No full textContrasting the climate change emergency represents one of
the major challenges of modern times. Knowing how people
represent ecology-related phenomena is crucial to inform
interventions aimed at promoting more effective proenvironmental
behaviors. Despite this, literature on the topic is
still scarce. To fill this gap, we asked 340 participants to rate
200 concepts—among which Ecological (N = 50, e.g.,
deforestation)—on numerous semantic dimensions (N = 39),
drawing insights from the literature on conceptual
organization. A Principal Component Analysis on our dataset
revealed the presence of three major components explaining
overall the variability of our set of concepts. Interestingly,
Ecological concepts had a major role in all of them. Indeed,
when compared to other conceptual categories—both related
(i.e., Natural—e.g., water—and Geographical/Geopolitical—
e.g., ocean, city) and not related (i.e., Technological—e.g.,
Internet) to the green domain—they figured among the most
abstract (Component 1), impacting our political, social, and
personal spheres (Component 2), scientific, emotionally
charged, and evoking sensorimotor experiences (Component 3)
concepts. Overall, our study has a threefold relevance. On a
theoretical side, it can contribute to enriching theories on
concepts by investigating a new semantic domain that
jeopardizes the concrete-abstract dichotomy; on a scientific
side, it might broaden categorization research by providing
semantic norms for new conceptual domains (the TECo
Database); on a societal side, it can enhance politics on these
timely themes
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
Abstract Concepts, Social Interaction, and Beliefs
No full textWhy might research on abstract concepts be relevant to literature on beliefs? We contend
that it is significant for various reason
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
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