1,720,955 research outputs found
Ruolo delle proprietà meccaniche e termodinamiche nell'attività dei sistemi biologici
No full textStoricamente, i campi della biologia strutturale e della fisiologia hanno trascurato l’approccio tipico della scienza dei materiali per lo studio dei sistemi biologici. Tuttavia, l’indagine delle proprietà fisiche – meccaniche e termodinamiche, ma anche ottiche e/o magnetiche – della materia biologica e del modo in cui queste caratteristiche rispondono alla modifica di fattori ambientali, può consentire di capire in modo più approfondito i processi funzionali e fisiologici che avvengono dalla nanoscala alla macroscala.
La necessità di un approccio biofisico deriva, in parte, anche dai progressi effettuati nel campo della medicina rigenerativa e, più in generale, nelle ricerche su biomateriali che devono interagire col corpo in un modo specifico e predicibile. In parallelo, lo sviluppo di nuove tecnologie – sia dal punto di vista teorico/computazionale che sperimentale – ha concesso nuovi strumenti per lo studio approfondito delle proprietà più strutturali dei sistemi biologici, dalle cellule, ai tessuti, ad interi organi.
In questo lavoro sperimentale, la microscopia a forza atomica (AFM) – insieme ad altre tecniche complementari, come l’aspirazione con micropipette (MAT) e la spettroscopia infrarossa (FTIR) – vengono impiegate per studiare e caratterizzare le proprietà meccaniche e termodinamiche di sistemi biologici diversi, in relazione allo specifico target di applicazione, che spazia, in questo caso, dalla farmacologia, alla medicina rigenerativa, all’ingegneria tissutale.
Dopo un’introduzione nella quale vengono specificate le principali motivazioni e viene tracciato il quadro dello stato dell’arte (Capitolo 1), viene affrontata la descrizione dei campioni biologici investigati (Capitolo 2) e delle tecniche sperimentali utilizzate (Capitolo 3). I metodi e i protocolli impiegati sono riportati in dettaglio nel Capitolo 4. Nel Capitolo 5 sono presentati i risultati relativi all’effetto di molecole di interesse farmacologico e in particolare neurosteroidi (allopregnanolone (Allo), isoallopregnanolone (isoAllo) e pregnenolone solfato (Preg-S)) su modelli di membrana biologica. Le variazioni delle proprietà meccaniche e termodinamiche sono contestualizzate nell’ambito dell’ipotesi dei lipid rafts. Nel Capitolo 6, le proprietà enantiospecifiche dei bilayer lipidici vengono valutate studiando l’effetto degli enantiomeri dei neurosteroidi impiegati (ent-Allo e ent-isoAllo) su modelli di membrana biologica. Il Capitolo 7 riguarda l’effetto dei neurosteroidi Allo e dehydroepiandrosterone (DHEA) – che hanno una provata funzione neuroregenerativa – su cellule rilevanti per il funzionamento del sistema nervoso centrale, sia per quanto riguarda la riorganizzazione delle strutture citoscheletriche, sia per ciò che concerne una modificazione delle proprietà meccaniche. Il Capitolo 8 è relativo allo studio di strutture di fibrina+cheratinociti di interesse per la medicina rigenerativa e, in particolare, per il trapianto della cornea. La caratterizzazione meccanica viene effettuata utilizzando, in questo caso, il modello poroelastico e i dati derivanti dagli esperimenti di indentation modulation. Infine, nel Capitolo 9 sono riassunti i principali risultati ottenuti e vengono delineate le possibili future prospettive di indagine.Historically, the fields of structural biology and physiology have tended to overlook materials-science approaches when investigating biological matter. However, studies of the physical - mechanical and thermodynamical, but also optical and/or magnetic - properties of biological systems and the investigation of how these features responds to changing environmental factors, provides opportunities to improve understanding of functional and physiological processes at all scales, from molecular and nanoscale to the
macroscale.
The emergence of biological materials science is due, in part, to the advent of regenerative medicine, as this discipline needs biomaterials that interact with the body in a specific, predictable manner. In parallel, the development of new technologies - both theoretical/computational and experimental - allows researchers the possibility to use new tools to study, in great detail, the structural properties of biological materials, whether cells,
tissue samples or complete organs.
In this experimental work we exploit Atomic Force Microscopy (AFM) - combined with other different and complementary techniques, like Micropipette Aspiration Technique (MAT) and Fourier Trasformed Infrared Spectroscopy (FTIR) - to study and characterize different biological samples, in order to have a better insight on their mechanical and thermodynamical properties, according to the specific target of application, which spaces from pharmacology to regenerative medicine and to tissue engineering.
After an introduction where the state of the art and the main motivations for this work are pointed out (Chapter 1), we present and describe the investigated materials (Chapter 2), as well as the employed experimental techniques (Chapter 3). The complete methods and protocols used for our characterization are reported in Chapter 4. In Chapter 5 we present the results concerning the effect of molecules of pharmacological interest like neurosteroids (allopregnanolone (Allo), isoallopregnanolone (isoAllo), pregnenolone sulfate (Preg-S)) on model lipid membranes. Mechanical and thermodynamical modification due to the presence of the neurosteroids are remarked and contextualized in the framework of the raft hypothesis. In Chapter 6 the effects of neurosteroids' enantiomers (ent-Allo and ent-isoAllo) on model lipid bilayers are studied in order to evaluate the enantiospecific properties of the membrane. Chapter 7 deals with the effects of the neurosteroids Allo and dehydroepiandrosterone (DHEA) - which are proved to have a neuroregenerative function - on cells relevant for the central nervous system, whether regarding the cytoskeleton reorganization or modifications in the mechanical properties.
Chapter 8 deals with the topographical and mechanical characterization of fibrin+keratinocytes samples for regenerative medicine and, in particular, for corneas transplantations. Data emerging from the characterization of the bare fibrin are for the first time analyzed in the context of the poroelastic theory and indentation modulation measurements are also presented. Finally, in Chapter 9 the results obtained in this work are briefly summarized and the main conclusions are presented, as well as future perspectives
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
Effect of neurosteroids on a model lipid bilayer including cholesterol: An Atomic Force Microscopy study
No full textAmphiphilic molecules which have a biological effect on specific membrane proteins, could also affect lipid bilayer properties possibly resulting in a modulation of the overall membrane behavior. In light of this consideration, it is important to study the possible effects of amphiphilic molecule of pharmacological interest on model systems which recapitulate some of the main properties of the biological plasma membranes. In this work we studied the effect of a neurosteroid, Allopregnanolone (3α,5α-tetrahydroprogesterone or Allo), on a model bilayer composed by the ternary lipid mixture DOPC/bSM/chol. We chose ternary mixtures which present, at room temperature, a phase coexistence of liquid ordered (Lo) and liquid disordered (Ld) domains and which reside near to a critical point. We found that Allo, which is able to strongly partition in the lipid bilayer, induces a marked increase in the bilayer area and modifies the relative proportion of the two phases favoring the Ld phase. We also found that the neurosteroid shifts the miscibility temperature to higher values in a way similarly to what happenswhen the cholesterol concentration is decreased. Interestingly, an isoform of Allo, Isoallopregnanolone (3β,5α -tetrahydroprogesterone or isoAllo), known to inhibit the effects of Allo on GABAA receptors, has an opposite effect on the bilayer properties
Effects of neurosteroids on a model membrane including cholesterol: A micropipette aspiration study
No full textAmphiphilic molecules supposed to affect membrane protein activity could strongly interact also with the lipid component of the membrane itself. Neurosteroids are amphiphilic molecules that bind to plasma membrane receptors of cells in the central nervous system but their effect on membrane is still under debate. For this reason it is interesting to investigate their effects on pure lipid bilayers as model systems. Using the micropipette aspiration technique (MAT), here we studied the effects of a neurosteroid, allopregnanolone (3α,5α-tetrahydroprogesterone or Allo) and of one of its isoforms, isoallopregnanolone (3β,5α-tetrahydroprogesterone or isoAllo), on the physical properties of pure lipid bilayers composed by DOPC/bSM/chol. Allo is a well-known positive allosteric modulator of GABAA receptor activity while isoAllo acts as a non-competitive functional antagonist of Allo modulation. We found that Allo, when applied at nanomolar concentrations (50-200 nM) to a lipid bilayer model system including cholesterol, induces an increase of the lipid bilayer area and a decrease of the mechanical parameters. Conversely, isoAllo, decreases the lipid bilayer area and, when applied, at the same nanomolar concentrations, it does not affect significantly its mechanical parameters. We characterized the kinetics of Allo uptake by the lipid bilayer and we also discussed its aspects in relation to the slow kinetics of Allo gating effects on GABAA receptors. The overall results presented here show that a correlation exists between the modulation of Allo and isoAllo of GABAA receptor activity and their effects on a lipid bilayer model system containing cholesterol
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
- …
