1,354,563 research outputs found
The potential of AFM in studying the role of the nanoscale amphipathic nature of (lipo)-peptides interacting with lipid bilayers
No full textAntimicrobial peptides (AMPs) and lipopeptides (LPs) represent very promising molecules to fight resistant bacterial infections due to their broad-spectrum of activity, their first target, i.e. the bacterial membrane, and the rapid bactericidal action. For both types of molecules, the action mechanism starts from the membrane of the pathogen agents, producing a disorganization of their phase structure or the formation of pores of different size altering their permeability. This mechanism of action is based on physical interactions more than on a lock-and-key recognition event and it is difficult for the pathogens to rapidly develop an effective resistance. Very small differences in the sequence of both AMPs and LPs might lead to very different effects on the target membrane. Therefore, a correct understanding of their mechanism of action is required with the aim of developing new synthetic peptides, analogues of the natural ones, with specific and more powerful bactericidal activity. Atomic force microscopy (AFM), with its high resolution and the associated force spectroscopy resource, provides a valuable technique to investigate the reorganization of lipid bilayers exposed to antimicrobial or lipopeptides. Here, we present AFM results obtained by ours and other groups on the action of AMPs and LPs on supported lipid bilayers (SLBs) of different composition. We also consider data obtained by fluorescence microscopy to compare the AFM data with another technique which can be used on different lipid bilayer model systems such as SLBs and giant unilamellar vesicles. The outcomes here presented highlight the powerful of AFM-based techniques in detecting nanoscale peptide-membrane interactions and strengthen their use as an exceptional complementary tool to in vivo investigations. Indeed, the combination of these approaches can help decipher the mechanisms of action of different antimicrobials and lipopeptides at both the micro and nanoscale levels, and to design new and more efficient antimicrobial compounds
Dal modello geotecnico del sottosuolo all’intervento di consolidamento del terreno di fondazione
No full textIl risultato principale dell’intervento di consolidamento eseguito sul terreno di fondazione del campanile dei Frari è certamente costituito dal nuovo andamento dei cedimenti del campanile. Tale evoluzione, se confermata nel prossimo futuro, sembra rispondere a tutti gli obbiettivi iniziali.
Naturalmente, durante ma soprattutto al termine dell’intervento, si è ritenuto opportuno andare a controllarne gli effetti anche sul terreno stesso. A questo proposito, sono stati effettuati sondaggi a carotaggio continuo e prove geotecniche in sito (prove penetrometriche e dilatometriche) per la valutazione sperimentale delle caratteristiche meccaniche del terreno conseguite con il trattamento di soil fracturing.
Si noti come un sostanziale miglioramento delle caratteristiche meccaniche del terreno (tanto in termini di resistenza quanto di rigidezza) venga ottenuto in corrispondenza dei cicli finali di iniezione, con andamento piuttosto variabile in conseguenza della presenza delle lame di miscela cementizia, che si sono venute progressivamente formando. Risulta peraltro confermata la marcata non linearità tra il miglioramento delle caratteristiche meccaniche del terreno trattato e l’intensità di trattamento, crescente con i vari cicli di iniezione, già evidenziata in occasione delle misure inclinometriche.
La diffusa presenza delle lame di miscela cementizia, di spessore compreso tra pochi decimi di mm fino a circa 3 mm, è stata inoltre direttamente individuata anche nel corso delle ispezioni dirette del terreno consolidato, eseguite dopo l’intervento mediante sondaggi a carotaggio continuo con prelievo di campioni indisturbati. La direzione prevalente delle lamelle è risultata sub-verticale, in direzione ortogonale alla tensione principale minima.
Dai campioni indisturbati di terreno sottoposti a prove di compressione in condizioni confinate (prove edometriche), si può infine riscontrare un’ulteriore conferma dell’aumento della rigidezza del terreno trattato rispetto alle medesime caratteristiche del terreno originario. I moduli edometrici sono riferiti ai rispettivi gradini di carico raggiunti durante le prove: essi raddoppiano per livelli tensionali di 50 kPa ed aumentano di circa il 20% per livelli tensionali di 400 kPa. Pertanto la sovraconsolidazione, determinatasi in ragione delle iniezioni di soil fracturing, appare più significativa per bassi livelli tensionali e tende progressivamente ad attenuarsi con la profondità.
Nel complesso, le varie indagini geotecniche eseguite al termine dell’intervento forniscono concordemente un notevole miglioramento delle caratteristiche meccaniche del terreno, ottenuto non soltanto grazie alla diffusa presenza delle lame di miscela cementizia all’interno del terreno, ma soprattutto in virtù dell’azione di sovraconsolidazione esercitata dalle iniezioni ripetute e selettive.
Il terreno perimetrale al masso fondale risulta pertanto decisamente rinforzato e, unitamente alle file pressoché continue di canne metalliche, dovrebbe ora essere in grado di fornire un maggior confinamento allo strato argilloso di fondazione, riducendo sensibilmente l’evoluzione dei cedimenti nel tempo
Surgical field isolation through rubber dam to prevent covid-19 exposure during tooth extraction: Case report
No full textBackground: At the beginning of 2020, a new pathogen named SARS-CoV-2 spread from China to the globe, becoming responsible for a potentially lethal acute respiratory syndrome: COVID-19. Direct contact and airborne contamination are the most frequent infection ways of SARS-CoV-2. During routine dental practice, SARS-CoV-2 transmission can occur through direct contact with mucous membranes, oral fluids, and contaminated instruments or inhalation of aerosol from infected patients. Introduction: Tooth extraction often involves exposure to blood and oral fluids, and the use of a rubber dam could be indicated to minimize direct contact and to decrease the amount of potentially infected droplets around the operatory field. The aim of this clinical case is to show how the use of a rubber dam could help in preventing or minimizing COVID-19 exposure during dental extraction. Materials and Methods: A 32-year-old patient reported severe pain and discomfort to an upper first molar due to a deep carious lesion and vertical tooth fracture. Under local anaesthesia, a rubber dam was placed, isolating the whole upper right sextant, and an atraumatic extraction was performed. Results: All three roots were intact, the bone septum was stable, and no oro-antral communication was present. A gauze swab was placed onto the socket and compressed slightly. After 5 minutes, the socket stopped bleeding, and both clamp and rubber dam, were removed. Conclusion: Within the limits of this single case report, the use rubber dam prior to tooth extraction could be a useful device to decrease aerosol spread and exposure to blood
Daptomycin Strongly Affects the Phase Behavior of Model Lipid Bilayers
No full textDaptomycin (DAP) is a calcium-dependent cyclic lipopeptide with great affinity for negatively charged phospholipids bearing the phosphatidylglycerol (PG) headgroup and has been used since 2003 as a last resort antibiotic in the treatment of severe infections caused by Gram-positive bacteria. The first step of its mechanism of action involves the interaction with the bacterial membrane, which not only represents a physical barrier but also accommodates transmembrane proteins, such as receptors, transporters, and enzymes, whose activity is crucial for the survival of bacteria. This results in a less efficient development of resistance strategies by pathogens compared to common antibiotics that activate or inhibit biochemical pathways connected to specific target proteins. Although already on the market, the molecular mechanism of action of DAP is still a controversial subject of investigation and it is most likely the result of a combination of distinct effects. Understanding how DAP targets the membrane of pathogens could be of great help in finding its analogues that could better avoid the development of resistance. Here, exploiting fluorescence microscopy and atomic force microscopy (AFM), we demonstrated that DAP affects the thermodynamic behavior of lipid mixtures containing PG moieties. Regardless of whether the PG lipids are in the liquid or solid phase, DAP preferably interacts with this headgroup and is able to penetrate more deeply into the lipid bilayer in the regions where this headgroup is present. In particular, considering the results of an AFM/spectroscopy investigation, DAP appears to produce a stiffening effect of the domains where PG lipids are mainly in the fluid phase, whereas it causes fluidification of the domains where PG lipids are in the solid phase
Term formation as a collaborative practice: between translation and cooperation among experts
No full textThis study describes a 19th-century debate among scholars on the periodisation of English medieval
architecture. Through this example, in this article, I explore the creation of architectural vocabulary
as a collaborative act, whereby the cooperation among experts shaped concepts and terms. At the
same time, a translational perspective is offered through the comparison of English and French
nomenclatures, which contributed to the creation of a European code of medieval architecture. To
illustrate such collaborative practices of terminologists, original quotes from the debate are presented
and discussed.
The analysis reveals that while “proper” term translation was not considered as possible,
given the exclusively national character of architecture, experts drew inspirations from foreign
scholars in the formation of terms, thus fostering international communication and exchange of
ideas. Moreover, term formation, as theorised by Sager (1990), is described as a collaborative,
and sometimes non-collaborative practice, where multiple actors and factors, including the co-
existence of an official and several conversational nomenclatures, contributed to making scientific
language evolve
Ancora su Coluccio Salutati. A proposito del ms. A. 146 dell'Archiginnasio di Bologna
No full textScheda di descrizione e studio paleografico del ms. A. 146 della Biblioteca Comunale dell’Archiginnasio di Bologna, testimone trecentesco dell' "Epitoma rei militaris" di Vegezio appartenuto a Coluccio Salutati
Catalogazione, storia della scrittura, storia del libro. I manoscritti datati d'Italia vent'anni dopo, a cura di T. De Robertis e N. Giovè Marchioli
No full textRecensione del seguente volume: "Catalogazione, storia della scrittura, storia del libro. I manoscritti datati d'Italia vent'anni dopo", a cura di T. De Robertis e N. Giovè Marchioli, Firenze, SISMEL- Edizioni del Galluzzo, 2017 (mediEVI, 16). Il libro contiene gli Atti del Convegno Internazionale di Studi, svoltosi presso la Biblioteca Malatestiana di Cesena nel dicembre 2014, in occasione del ventennale del progetto di ricerca "Manoscritti datati d'Italia", promosso dall'associazione Italiana Manoscritti Datati (AIMD)
Harmonising concepts and terms for the development of knowledge. A study on the need for names and the necessity for harmonisation in the 19th century
No full textMeccanobiologia di sistemi biologici: da doppi strati lipidici a cellule in-vitro
No full textLe proprietà meccaniche dei sistemi biologici hanno una grande importanza nel determinare il loro comportamento. Molti potenziali farmaci possono modificare le proprietà meccaniche della membrana biologica e indirettamente modulare la funzione di proteine di membrana. Analogamente, molti stati patologici a livello cellulare presentano un fenotipo con proprietà meccaniche alterate e la modifica di tali proprietà è tipicamente il risultato di una riorganizzazione del citoscheletro. Allo stesso tempo, le cellule sondano le proprietà reologiche della matrice extracellulare (ECM) attivando, a seconda della risposta ottenuta, diversi percorsi biochimici. Tali fenomeni sono spesso caratterizzati da una riorganizzazione citoscheletrica a seguito di stimoli periodici, come avviene ad esempio nel sistema cardiovascolare o nei polmoni. La scienza che tratta questi fenomeni è la meccanobiologia. Il lavoro di questa tesi di dottorato è dedicato all’analisi delle proprietà meccaniche di costituenti biologici, da semplici modelli di membrana, come doppi-strati-lipidici supportati (SLB) e vescicole giganti unilamellari (GUV), a sistemi quali colture cellulari in-vitro. Le tecniche di indagine usate hanno coinvolto: microscopia ottica in contrasto di fase, DIC e fluorescente; microscopia a forza atomica (AFM). Sono stati sviluppati, all’interno della tesi, metodi di analisi e dispositivi dedicati per specifiche applicazioni e misure di campioni. È stato progettato, testato e impiegato un incubatore per esperimenti di live-cell imaging da integrare direttamente sul tavolino (on-stage) di un microscopio ottico. Sono stati ottenuti simultaneamente parametri di migrazione di cellule esposte a diversi trattamenti, o poste su substrati aventi diversa rigidità meccanica. Lo stesso incubatore è stato ridisegnato per poter alloggiare uno stretcher uniassiale in grado di fornire al substrato specifiche funzioni periodiche di deformazione e valutare la conseguente risposta delle cellule in termini di migrazione e polarizzazione. Tra i metodi di indagine, è stata sviluppata l’analisi quantitativa di migrazione di singola cellula, ed è stato impiegato il modello “Persistence-Random-Walk”. Lo scopo era quello di analizzare l’effetto citostatico di un potenziale farmaco nelle cellule U87MG, usate come modello del glioblastoma multiforme. L’analisi effettuata ha infatti mostrato l’efficacia sia citostatica che antimitotica della molecola. Sono stati indagati inoltre i possibili meccanismi biochimici alla base di tali effetti. Nel contesto dei SLB e GUV è stata implementata rispettivamente l’analisi sulla tensione di linea di domini che simulano lipid-rafts e la costante di bending, basandosi sulla teoria delle fluttuazioni di membrana. Nel primo caso sono stati confrontati i risultati sulla misura della tensione di linea di miscele ternarie costituite da diverse componenti rilevanti nella formazione di lipid-rafts. Nel secondo caso, è stato valutato il ruolo di molecole esogene (peptidi antimicrobici e lipopeptidi) nella determinazione della costante di bending. Nella caratterizzazione visco-elastica del citoscheletro con AFM, è stato implementato un software basato sul modello di Ting, in grado di estrapolare i parametri viscoelastici dalle singole curve andata-ritorno. Si è studiato l’effetto del potenziale farmaco prima citato, sulle proprietà reologiche di cellule U87MG al fine di correlare migrazione e proprietà meccaniche cellulari. Sono stati sviluppati software dedicati alla ricerca di eventi Jump-Through-Force nell’analisi di SLB, e di eventi di estrazioni di tubi durante la retrazione della punta AFM sulla membrana plasmatica come possibile metodo per evidenziare variazioni di proprietà reologiche di membrane esposte a diversi trattamenti farmacologici.Mechanical properties of biological systems play a crucial role for their own behavior. As an example, many potential drugs could modify mechanical properties of the biological membrane and indirectly modulate transmembrane protein functions. Similarly, many pathological conditions at the cellular level are characterized by a phenotype with altered mechanical properties, and these alterations are due to cytoskeleton reorganization. At the same time, cells continuously probe rheological properties of extracellular matrix (ECM) enabling, depending on response obtained by the substrate, different downstream signaling cascades. In many cases, cytoskeleton reorganization occurs also when cells are experiencing periodic mechanical stimuli, as it happens for example in the cardiovascular system or in lungs. All these aspects are treated by a recent branch of physic and biology sciences: “Mechano-biology”. This PhD thesis work has been devoted to study some specific aspects of mechanical properties of biological systems: from simple models of the biological-membrane, like supported-lipid-bilayer (SLB) or giant-unilamellar-vescicle (GUV), to in-vitro cells. Investigation techniques exploited in this work include: phase-contrast optical microscopy, DIC and fluorescence microscopy and atomic force microscopy (AFM). In the thesis we developed analysis-methods and devices dedicated to specific application and measurements of biological samples. It has been designed, tested and employed successfully an on-stage cell incubator for live cell imaging. From time-lapse microscopy experiments we obtained different quantitative migration parameters both for cell exposed to different drugs and for cells seeded on substrates with different mechanical rigidity. The same cell incubator has been modified to include an uniaxial stretcher, able to provide specific periodic deformation functions to the substrate on which cells are growing, and we studied the effect of the periodic stimulation on cell migration and polarization. Among the different analysis methods, a single cell migration analysis protocol has been developed, exploiting the “Persistence-Random-Walk” model. The ultimate goal was that of analyzing the cytostatic effect of a potential drug for U87MG cell line, employed as model of the glioblastoma multiforme disease. The analysis has in fact shown the efficiency of this molecule for both migration and replication of this cell line. Furthermore, possible biochemical mechanisms of action involved in these effects have been investigated. In the context of SLBs and GUVs a line tension analysis of domains recapitulating lipid-raft and a bending constant measurement have been implemented, both based on Flickering spectroscopy theory. In the former case, line tension results of ternary mixture containing different components relevant for lipid-rafts formation have been compared for different lipid compositions. In the latter case, the role of exogenous molecules (antimicrobial peptides and lipopeptides) on the bending constant has been investigated. In viscoelastic characterization of the cell cytoskeleton through AFM, a Ting model-based software has been implemented, allowing to extrapolate viscoelastic parameters from single indentation-retraction curves. Using this method, the effect of the previously mentioned potential drug has been investigated, trying to correlate rheological properties to migration capabilities of U87MG. Finally, software dedicated to Jump-Through-Force curves by AFM to identify specific events on SLB, and tether pulling events during AFM tip retraction on plasma-membrane have been developed; in order to find possible methods to highlight variations in rheological properties of membrane exposed to different drug treatments
A modified intraoral resin mouthguard to prevent self-mutilations in lesch-nyhan patients
No full textLesch-Nyhan syndrome, described in 1964 by Lesch and Nyhan, is a X-linked recessive disorder, occurring in 1 : 100000 to 1 : 380000 live births. LNS is characterized by a decrease in activity of hypoxanthine guanine phosphoribosyl transferase, an enzyme involved in purine metabolism, resulting in overproduction of uric acid. Hyperuricemia and neurological features including choreoathetoid spasticity, self-mutilation, and mental retardation clinically characterize this syndrome. In LNS patients the typical feature is loss of tissue from biting themselves with partial or complete amputation of fingers, lips, and tongue. The self-mutilation compares with the eruption of the deciduous teeth. Several drugs trials have been administered to improve self-destructive behavior and invasive treatment approaches, such as extractions of teeth and orthognathic surgery, have been suggested with variable effectiveness. Nowadays prevention is, therefore, the standard of care. The role of dentistry is essential in the management of the self-mutilating behavior, because the teeth represent the main self-injury instrument. This report presents a revision of various therapeutic approaches to manage self-destruction, highlighting the effectiveness of a preventive treatment. It describes a new technique: a resin mouthguard, realized at Gaslini Hospital, to obtain immediate healing of the oral lesions, confirmed in the follow-up period
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