39 research outputs found

    The central proline rich region of POB1/REPS2 plays a regulatory role in epidermal growth factor receptor endocytosis by binding to 14-3-3 and SH3 domain-containing proteins

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    Background. The human POB1/REPS2 (Partner of RalBP1) protein is highly conserved in mammals where it has been suggested to function as a molecular scaffold recruiting proteins involved in vesicular traffic and linking them to the actin cytoskeleton remodeling machinery. More recently POB1/REPS2 was found highly expressed in androgen-dependent prostate cancer cell lines, while one of its isoforms (isoform 2) is down regulated during prostate cancer progression. Results. In this report we characterize the central proline rich domain of POB1/REPS2 and we describe for the first time its functional role in receptor endocytosis. We show that the ectopic expression of this domain has a dominant negative effect on the endocytosis of activated epidermal growth factor receptor (EGFR) while leaving transferrin receptor endocytosis unaffected. By a combination of different approaches (phage display, bioinformatics predictions, peptide arrays, mutagenic analysis, in vivo co-immunoprecipitation), we have identified two closely spaced binding motifs for 14-3-3 and for the SH3 of the proteins Amphiphysin II and Grb2. Differently from wild type, proline rich domains that are altered in these motifs do not inhibit EGFR endocytosis, suggesting that these binding motifs play a functional role in this process. Conclusion. Our findings are relevant to the characterization of the molecular mechanism underlying the involvement of POB1/REPS2, SH3 and 14-3-3 proteins in receptor endocytosis, suggesting that 14-3-3 could work by bridging the EGF receptor and the scaffold protein POB1/REPS2. © 2008 Tomassi et al; licensee BioMed Central Ltd

    Inclusione di un estratto di farina di grano fermentata in liposomi per la somministrazione orale: effetto su cellule intestinali HT-29

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    Lisosan G (LG) è una farina di grano fermentata contenente polifenoli, acido alfa-lipoico, acidi grassi polinsaturi e vitamine con proprietà antiossidanti e antinfiammatorie (Gabriele et al., 2018). Questi costituenti sono spesso caratterizzati da instabilità chimica, bassa solubilità e biodisponibilità nonché scarso assorbimento, che ne limitano l'applicazione terapeutica. L‘impiego di liposomi, sistemi nanoparticellati che possono incorporare composti con diverse proprietà chimico-fisiche, consente di proteggere le componenti bioattive dalla degradazione, aumentarne la solubilità, modularne il rilascio e facilitarne la diffusione attraverso le membrane biologiche (Hendawy, 2021). In questo studio, abbiamo formulato e caratterizzato liposomi contenenti l'estratto acquoso di LG per la somministrazione orale. È stato utilizzato il polimero enterico Eudragit® per proteggere i liposomi dall'ambiente gastrico, e sono state ottenute vescicole unilamellari di circa 100 nm. È stata quindi valutata la Ioro stabilità in fluidi gastrointestinali simulati, la Ioro potenziale tossicità nelle cellule intestinali umane HT-29, tramite saggio MTT e gli effetti sulla produzione di specie reattive dell'ossigeno (ROS) intracellulari, rilevati in seguito all'esposizione delle cellule alla DCFH-DA, una sonda fluorescente permeabile alla membrana cellulare. I risultati hanno mostrato gastro-resistenza degli Eudragit-liposomi, che non hanno alterato la vitalità delle cellule HT-29, non differendo tra LG libero e LG internalizzato nel liposoma. lnoltre, gli Eudragit-liposomi non hanno indotto variazioni dei livelli intracellulari dei ROS. I liposomi rappresentano pertanto un sistema efficiente per la veicolazione di estratti ottenuti da alimenti complessi e, se formulati correttamente, possono offrire protezione dalla degradazione fisiologica senza effetti tossici sulle cellule intestinali

    Hot potassium carbonate-based CO2 capture with vacuum solvent regeneration: pilot plant experimental tests and process simulation

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    reservedCarbon capture technologies have become crucial in reducing greenhouse gas emissions, combatting climate change, and reaching carbon neutrality while transitioning away from fossil fuels and petroleum-based industries. The hot potassium carbonate (HPC) process has emerged as an extremely promising solution among these technologies due to its effectiveness in capturing carbon dioxide (CO2) from a broad range of industrial flue gases. Offering potential advantages such as being environmentally friendly and requiring lower energy consumption at the regeneration stage, potassium carbonate (K2CO3) is being proposed as a greener alternative to the more established amine-based methods. However, the K2CO3 process also faces challenges that necessitate additional research to ensure high CO2 absorption capacity and promote its wider application at the industrial level. This master’s thesis investigates the performance of a hot potassium carbonate-based CO2 capture process with vacuum solvent regeneration through pilot plant experimental tests and process simulation. The first chapter provides a comprehensive review of the existing CO2 capture technologies, emphasising the benefits and drawbacks of potassium carbonate-based techniques. The feasibility and efficiency of the proposed process are evaluated by carrying out a pilot plant experimental campaign. The flexible structure of the pilot plant enables the configuration of many different process layouts, encompassing a wide range of operating parameters, to investigate the process's performance under different conditions. Given the scope of the thesis, three levels of stripping pressures were examined while modifying the other two parameters, namely the absorber pressure and the solvent flowrate, which were studied at two and four distinct levels, respectively. The second chapter discusses the experimental design and technique, while the third summarises the main findings. The thesis concludes with a process simulation using Aspen Plus® software to compare experimental and simulated results, providing useful insights into the influence of process variables on the overall carbon capture performance. The outcomes of this research contribute to the ongoing efforts in developing sustainable CO2 capture technologies and provide a solid basis for further process optimisation, potentially paving the way for the use of HPC-based CO2 capture in industrial settings

    STUDIO DEI MECCANISMI PROTETTIVI DEL NaHS SULLA CITOTOSSICITA' INDOTTA DAL CISPLATINO NELLE CELLULE DELL'ORGANO DI CORTI (HEI-OC1)

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    Le cellule “House Ear Institute-Organ of Corti 1” (HEI-OC1) sono cellule che derivano dall’organo uditivo di Corti del topo transgenico Immortomouse ™. Queste cellule presentano marcatori molecolari caratteristici delle cellule sensoriali dell’organo di Corti e un’elevata sensibilità a farmaci ototossici, per questo sono utilizzate come modello in vitro per l’indagine dei meccanismi molecolari coinvolti nell’ototossicità. Uno dei farmaci che causano ototossicità è il cisplatino, un chemioterapico utilizzato nella cura di vari tipi di tumori solidi quali tumori alle ovaie, al polmone, al cervello al collo fino e al testicolo. Il cisplatino può infatti causare danni in varie aree dell’orecchio interno inducendo la morte, o mancata funzionalità, delle cellule ciliate dell’organo del Corti e la perdita uditiva bilaterale, permanente alle alte frequenze. La tossicità causata dal cisplatino è da attribuire sia al legame dei suoi prodotti di idrolisi con il DNA, sia all’aumentata produzione di specie reattive dell’ossigeno (ROS), che portano all’arresto del ciclo cellulare e alla morte. Lo scopo della presente tesi è di indagare se diverse sostanze con attività antiossidante (quercetina, lisosan G, NaHS) aumentino la vitalità delle cellule HEI-OC1 trattate con cisplatino. Sono stati condotti esperimenti di immunoblotting per individuare l’espressione di marcatori di autofagia (LC3-II) e di proteine coinvolte nel meccanismo di morte cellulare indotto da cisplatino quali p53, Akt ed ERK1/2. Inoltre sono state quantificate le attività delle caspasi 3 (caspasi esecutrice dell’apoptosi), 8 e 9 e la formazione dei ROS. Lo studio in oggetto ha evidenziato la protezione dose-dipendente del NaHS, dalla citotossicità del cisplatino. NaHS è in grado di diminuire la produzione di ROS, l’attività della caspasi 3 e della caspasi 8. I risultati suggeriscono quindi il NaHS come possibile agente protettivo nei confronti dell’ototossicità indotta dal cisplatin

    La tradición o la endeblez de lo grande

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    Exploración de la idea de tradición en la obra del filosofo colombiano Nicolás Gómez Dávila a través de una selección de escolios, notas y textos contrastados con algunos autores clásicos y la novela El GatopardoAn exploration of the idea of tradition in the works of the Colombian philosopher Nicolás Gómez Dávila. The investigation is done through the selection of various scholia, which are then contrasted with classical authors and the Leopard; the best-known work of Italian writer Giussepe Tomassi di LampedusaLiteratoPregrad

    Tackling the challenges of the oral administration of a fermented flour extract with liposomes: Effect on intestinal HT-29 cells

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    LisosanG is a fermented flour that contains polyphenols, polyunsaturated fatty acids, vitamins, and alpha-lipoic acid with antioxidant/anti-inflammatory properties. These compounds are often characterized by instability, low solubility/bioavailability, and poor absorption that restrict their application in therapy. These problems can be solved by using delivery systems among which liposomes have emerged as prominent candidates. Liposomes can load compounds with varied physico-chemical properties, providing protection from degradation, increased solubility, modulation of release, and facilitated diffusion across biomembranes. Lisosan G liposomes tailored for oral administration were prepared. Eudragit® enteric polymer was added to protect the liposomes from acidic pH. The Eudragit-liposomes were around 100 nm and unilamellar. They were resistant to acidic conditions and did not alter cell viability, nor intracellular ROS levels. These findings confirm that liposomes are an efficient system for the loading of multicomponent-based extracts and that, when properly formulated, can offer protection from physiological degradation, and be safely applied to cells.The authors wish to thank Agrisan Srl for providing Lisosan G. Jaume Caelles, from the SAXS-WAXS service at IQAC, is acknowledged for helping with the SAXS determinations.Peer reviewe

    Depression is associated with increased disease activity and higher disability in a large Italian cohort of patients with rheumatoid arthritis

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    Depression is a quite common comorbidity in patients with rheumatoid arthritis (RA) and is thought to influence its severity. This study aims to estimate, in a large cohort of Italian patients with RA, the prevalence of depression and to investigate the clinical correlates of depression in terms of disease activity and disability

    San Felipe los Alzati: Michoacán

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    La información de esta miniguía se basa en los trabajos de los arqueólogos Otto Schondube Baumbach, Jesús Teja Andrade, Wanda Tomassi de Magrelli y Estela Peña DelgadoEl asentamiento formaba parte de la frontera oriente del señorío tarasco. Se desconoce el nombre prehispánico del lugar; en la época colonial se llamó San Felipe Calvario, y en 1895, éste último se le cambió por el apellido Los Alzati, en honor de los hermanos José María, Marcos y Darío, héroes locales de la época de la intervención francesa. Las exploraciones arqueológicas llevadas a cabo en el sitio han sido escasas, por lo que sólo se ha descubierto una pequeña parte que corresponde a la zona ceremonial, ésta es, el área visitable.</p

    The Ecovillage of Pescomaggiore (L'Aquila) Birth and death of a self-determined post-disaster community (2009-2014)

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    Purpose - The purpose of this paper is to aim at exploring the relationship between community building and the changes occurred in the context of a post-disaster self-built ecovillage (EcoVillaggio Autocostruito (EVA)), spontaneously born after the L'Aquila earthquake in 2009. The community eventually dissolved in 2014, following a series of changes in the organization, that resulted in an increasingly centralized decision-making process, and in individual and community relationships, that were fueled by conflicts and contrasts.   Design/methodology/approach - Through a self-ethnography method, the paper provides the insider perspective of the lead author who was a part of EVA since the beginning. Self-ethnography allowed developing a narrative of EVA across its life course.   Findings - Findings reveal that the community into EVA was initially pursuing community-building goals through self-construction, sustainability, mutuality and reciprocity relationships out of market. However, several events occurred and changed community goals, organization and decision making. Eventually, individual goals and vertical decision making emerged among the community members, leading to the death of EVA.   Research limitations/implications - The paper just considered those main events that marked the collective and individual life of the lead author since the beginning until the end of the ecovillage. Others events, equally important, were not considered due to word length. In addition, self-ethnography is still considered by some authors as a subjective method.   Originality/value - The paper is one of the few exploring community experiences into post-disaster ecovillages. Moreover, there are no papers investigating post-disaster ecovillages through a self-ethnography approach. Therefore, the paper offers an innovative and original perspective on the under-investigated topic of post-disaster ecovillages and employs a promising research method in disaster studies
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