1,721,084 research outputs found
Il silenzio significativo come misura di semplificazione dell'attività edilizia: dubbi e prospettive
L'articolo si occupa di esaminare l'istituto del silenzio significativo al fine di valutare l'impatto della semplificazione amministrativa sull'attività edilizia
Il silenzio significativo come misura di semplificazione dell'attività edilizia: dubbi e prospettive
L'articolo si occupa di esaminare l'istituto del silenzio significativo al fine di valutare l'impatto della semplificazione amministrativa sull'attività edilizia
Thermodynamic Assessment of the Interaction of Food Fatty Acids with Pancreatic Model Membranes: Links Between Obesity and T2DM
Il presente lavoro ha avuto come obiettivo la realizzazione e lo studio calorimetrico di membrane cellulari modello allo scopo di simulare al meglio le membrane delle cellule β di Langerhans. In particolare ci si è focalizzati sull’influenza della composizione e delle dimensioni di tali membrane sulla loro stabilità. La successiva aggiunta di tre acidi grassi liberi (FFAs) alimentari, la quale mira a riprodurre l’effetto dell’elevata concentrazione ematica di FFAs tipica dei soggetti obesi e/o affetti da Diabete Mellito di Tipo 2 (T2DM) sul doppio strato fosfolipidico cellulare, ha permesso di evidenziarne e quantificarne gli effetti termodinamici su tali sistemi in relazione alla natura dell’acido.The aim of this work was the preparation and the calorimetric study of model cell membranes in order to simulate as best as possible the Langerhans β-cells’ membranes. Specifically, it was focused on the influence of the composition and the size of such model membranes on their stability. The consequent addition of three food Free Fatty Acids (FFAs), which aims to mimic the effect of high blood FFAs concentration typical of obese subjects and/or ones affected by Type 2 Diabetes Mellitus (T2DM) on the cell phospholipid bilayers, allowed to highlight and quantify their thermodynamic effects on such systems in relation to the nature of the acids
Calorimetric study of new model cell membranes to assess the influence of food fatty acids and Ca2+ in the frame of T2DM onset and progression
L’obiettivo di questo progetto di tesi di dottorato è quello di preparare e caratterizzare (termodinamicamente e spettroscopicamente) delle membrane modello che simulino al meglio i doppi strati fosfolipidici delle cellule β di Langerhans al fine di comprendere gli effetti della composizione lipidica e dello stress di origine alimentare (alte concentrazioni di Ca2+ e FFA) sulla stabilità di membrana. La successiva interazione di hIAPP con le membrane modello aiuterà a comprendere il peso della stabilità delle membrane cellulari nella patogenesi del T2DM.The aim of this PhD thesis research project is to prepare and characterize (thermodynamically and spectroscopically) model membranes which simulate as possible the phospholipid bilayers of the Langerhans β-cells in order to understand the effects of the lipid composition and the action of foodborne stress (high Ca2+ and FFA concentrations) on membrane stability. Furthermore, the interaction between these model membranes and hIAPP will be studied in order to highlight the role of cell membrane stability on the pathogenesis of T2DM
Il principio dello sviluppo sostenibile
Il capitolo analizza il principio dello sviluppo sostenibile, ripercorrendone l'evoluzione dalle origini internazionali fino alla codificazione ad opera del Codice dell'ambiente. Secondo l'Autore il principio incarna la matrice di doverosità del diritto ambientale ed è necessario analizzare il legame che vi è tra principi giuridici ed etica.
Il libro è frutto del lavoro di un gruppo di studiosi che si riunisce periodicamente per discutere dell'evoluzione del diritto amministrativo
Calorimetric approach to biomembrane thermodynamics: spotting the key points
The investigation of the forces that drive the self-assembly of phospholipid bilayers and that induce a particular thermodynamic behaviour is crucial for the determination of their roles in biological environments. For this reason, proper consideration should be paid to both endogenous and exogenous factors involved in biomembrane stability.
In this frame, a stepwise study of vesicles with different morphology and lipid composition was performed through high-sensitivity differential scanning calorimetry at physiological pH with the purpose of comprehending the role played by some of the main factors that contribute to the thermodynamic stability of cell membranes, e.g., lamellarity, curvature, phospholipid/non-phospholipid composition [1,2].
The nature and the magnitude of the effects arising from the interaction of lipid membranes with several external agents, such as proteins, lipids and other compounds, have also been evaluated in different case studies [3,4]. The high sensitivity of the DSC technique in revealing modifications in membrane thermodynamic stability is noteworthy for gaining insights on molecular aspects of the interaction mechanism, leading to several applications in biological, food and pharmaceutical fields
Proteins and Calorimetry: from diluted solutions to food systems
Thermal analysis and calorimetry are widely used for the characterization of bio-systems. The rather well defined general picture of the field implies the use of techniques and theoretical approaches that depend not only on the chemical peculiarities of the system (proteins, membranes, etc.) but mainly on its status with respect to the aqueous medium and the co-solutes.
In the case of proteins studied in diluted solutions, data obtained through HS-DSC (High Sensitive Differential Scanning Calorimetry) provide quantitative information about the mechanisms of the conformational transitions (protein denaturation) and the thermal stability of the macromolecules’ energetic domains, according to the formal expressions of thermodynamics and statistical mechanics.
The above picture is substantially modified in case proteins are included in a complex matrix where different bio-polymers (polysaccharides, etc.) are present in the same aqueous environment such as food. Indeed, these biopolymers are often thermodynamically incompatible, leading to the formation of several distinct aqueous phases in the system which may modify the protein’s properties both in terms of thermal stability and interactions. In these circumstances, the classical DSC technique is rather suitable for studying food products and processes mainly because it permits an easy evaluation of the relevant energetics of the systems on the basis of data collected from samples that do not demand any previous separation of the system’s components and that can therefore be reliably related to real products
Thermodynamic stability of complex model membranes: the role of composition, morphology and food fatty acids
Free Fatty Acids (FFAs) have been shown to be involved in several membrane-mediated cellular processes as lipid-assisted protein transport across the bilayer, fusion of lipid vesicles/cells and signalling for several cell mechanisms (e.g. insulin secretion). However, altered plasma FFAs levels typical of obese and/or diabetic subjects have been proposed to contribute to the onset and progression of type 2 diabetes mellitus through both their possible involvement in altered metabolic pathways and their direct action on cell membranes. Moreover, the action of FFAs has also been hypothesized to play a role in the interaction of amylin, an amyloidogenic protein, with cell membranes likely leading to the pancreatic β-cells failure by apoptosis.
Among several studies highlighting the FFAs-membrane interaction by means of spectroscopic, imaging, molecular dynamics and/or theoretical approaches, few works are devoted to a thermodynamic characterization of the role of FFAs on the overall membrane stability, however without considering the compositional and morphological complexity of real biological vesicles.
In such a frame, the present work was aimed at the calorimetric investigation of small, large and giant unilamellar vesicles prepared as pure and mixed systems of phospholipids with different length and unsaturation level. The preparation of a final model membrane was finally achieved mimicking the phospholipid bilayer of Insulin Secretory Granules (ISGs), vesicles located in the pancreatic Langerhans β-cells and which are responsible for insulin and amylin storage and secretion in response to nutrients intake. This study was performed through micro-DSC and allowed to discriminate each single thermodynamic contribution among the main factors that dictate the overall thermodynamic stability of these complex unilamellar systems (phospholipid unsaturations > phospholipid tail length > membrane curvature). The effect of three different FFAs, such as palmitic, stearic and oleic acids, added in different percentages both to a completely saturated ternary model membrane and to an unsaturated one (i.e. the final model membrane made by the saturated one including the 5% of 1,2-dioleoyl-sn-glycero-3-phosphocholine, DOPC) was eventually investigated highlighting a strong stabilizing effect as well as more pronounced phase segregations in the case of saturated acids, whereas the opposite effect was observed in the case of unsaturated FFAs. Moreover, the stabilizing effects deriving from saturated FFAs were more pronounced in less stable membranes, i.e. the unsaturated one, whereas the destabilizing effects deriving from the unsaturated FFAs were more pronounced in more stable membranes, i.e. the completely saturated one
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