282 research outputs found

    Assessing FOXA1-driven mRNA processing in prostate cancer with Nanopore long-read sequencing

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    Despite advances in the diagnosis and treatment of early stage of prostate cancer (PC), there are few therapeutic options for end-stage metastatic castration-resistant PC. The disease is difficult to tackle in part due to considerable phenotypic heterogeneity, underpinned by genomic alterations within different oncogenes or tumor suppressors. FOXA1 is the sly key oncogene of PC. As a pioneer transcription factor, FOXA1 opens up chromatin for DNA binding by distinct factors to drive PC initiation and progression to metastasis. We recently revealed a novel role for FOXA1 in orchestrating alternative splicing regulation in PC impacting patient survival. However, to which extent FOXA1 may be considered a guardian of the transcriptome is still to be determined. In this talk will show you how we addressed this challenge exploiting direct mRNA Oxford Nanopore sequencing. In particular I will discuss our data on FOXA1-mediated regulation of co- and post-transcriptional mRNA processing in PC

    A Combined Approach for the Analysis of Ocular Fluid Dynamics in the Presence of Saccadic Movements

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    One of the main ocular diseases is age-related macular degeneration, actually treated with antibodies injections into the eye. This problem has been faced by computational approaches, taking into account either the influence of the tissues surrounding the vitreous, or the saccades. The aim of this work is to propose a combined fluid dynamic model of the vitreous chamber that analyses the impact of the saccades on the fluid dynamic mechanisms. The ocular vitreous humor was modeled considering liquefaction occurring in presence of age-related macular degeneration. We identified two kinds of boundary conditions, one related to the physiological environment outside the chamber, and one related to the saccades. The scleral hydraulic conductivity was evaluated by means of experimental permeability tests. An exponential decay was used to describe the trend of the scleral hydraulic conductivity with the acting pressure drop. The streamline analysis shows two main stagnant regions on the equatorial plane and peculiar fluid dynamics in absence of saccades. This study demonstrates the major role played by the saccades in determining the fluid dynamic mechanisms inside the vitreous chamber of the eye and represents a powerful tool to investigate vitreous dynamics and its relation to clinical issues

    Evaluation of the ocular fluid dynamic effects on intraocular magnesium-based device: A comparison between CFD and FSI approaches

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    Magnesium is an essential element for the ocular functions and used for the realization of medical de- vices due to its low corrosion resistance, bioresorbable nature and biocompatibility. Wet age-related mac- ular degeneration is one of the main causes of blindness with patients treated by intravitreal injections of inhibitor drugs. According to the need to reduce the number of injections, the development of new drug delivery devices able to extend the therapeutical outcomes is mandatory and magnesium can be considered as a promising candidate. The aim of the work concerns the evaluation of the ocular fluid dy- namic role on a magnesium-based device placed in the vitreous chamber. Particularly, the fluid-induced shear stress field on the surfaces in contact with the liquefied vitreous was studied. Both computational fluid dynamic and fluid-structure interaction approaches were proposed and then compared. Saccadic motion was implemented to recreate the vitreous fluid dynamics. High changes in terms of fluid-induced shear stress field varying the CFD and FSI numerical approaches and kinematic parameters of the saccadic function can be noticed. The comparison between CFD and FSI approaches showed minor significant dif- ferences and both implementations suggested the possibility to obtain a uniform and controlled corrosion of the device

    A drug delivery analysis of large molecules in ocular vitreous chamber: Dependency on saccadic movements after intravitreal injection

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    The purpose of this study is to investigate the effect of vitreous sloshing induced by saccades on the intravitreal delivery of large molecule drugs. The vitreous body was considered in its age-related liquefaction condition. Fluid dynamics and large molecule distribution were described by the coupling of mass conservation's and Fick's laws with continuity and momentum equations for a Newtonian incompressible fluid in a 3D unsteady analysis. Two injection sites were analyzed, in both the mixing effect of a 50° periodic saccade leads to uniform drug distribution in 30 s of simulation, the initial bolus site being left after 3 s of simulation. In absence of saccadic movements, the dominant transport contribution is the diffusive one and large molecules hardly reach their uniform distribution inside the vitreous cavity. A model describing the intravitreal distribution of large molecules in presence of saccades was developed, improving the understanding of drug transport mechanism after an intravitreal injection and highlighting how advection contribution enhances its distribution in the vitreous chamber

    Rigenerare beni comuni: il valore educativo della partecipazione

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    Da diversi anni a questa parte sempre più comuni italiani hanno iniziato ad adottare regolamenti o patti di collaborazione per la “rigenerazione di beni comuni”: si tratta di accordi fondati sul principio di sussidiarietà che, attraverso atti amministrativi di natura non autoritativa, consentono ad amministratori e cittadini di intraprendere azioni di cura o presa in carico di beni materiali, immateriali o digitali riconosciuti come funzionali al benessere individuale e collettivo. Nel contributo che si propone all’interno del panel “pedagogia e politica”, questo genere di iniziative vengono lette attraverso la prospettiva pedagogica per le ricadute sul piano educativo che lo sviluppo di comunità presuppone, restituendo proprio alla politica il suo significato più autentico di responsabilità condivisa dell’interesse comune. Attraverso l’analisi documentale di decine di regolamenti comunali, si riconosce come già nell’uso dei termini, questi dispositivi presentino significative assonanze con il linguaggio pedagogico – responsabilità, sostenibilità, prossimità, inclusione – che inducono a considerarli esempi virtuosi della transizione in atto nel nostro sistema di welfare da una logica assistenziale a una logica generativa. Si tratta di un modo diverso di declinare i rapporti fra amministrazioni e cittadinanza, reso possibile anche dalla capillare azione di operatori sociali ed educativi sui territori: sono soprattutto queste figure, infatti, a fare da mediatori nelle pratiche di amministrazione condivisa e cura dei beni comuni e a presidiare quegli avamposti in cui le istanze della (buona) politica e quelle dei cittadini si incrociano
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