1,722,493 research outputs found
La geografia di Domenico Ciampoli nella raccolta di novelle Cicuta.
No full textUn'interpretazione geografica della raccolta di novelle Cicut
Establishment of a new cell model to identify drugs curtailing axonal mitochondria depletion in ADOA retinal ganglion cells
No full textAutosomal dominant optic atrophy (ADOA) is a hereditary optic neuropathy characterized by the progressive bilateral loss of vision for which no treatment currently exists. Mutations in the nuclear encoded mitochondrial protein Optic Atrophy 1 (Opa1) are associated with ADOA which affect primarily Retinal Ganglion Cells (RGCs). Upon RGC death, the optic nerve composed of RGC axons degenerates resulting in blindness. The Scorrano lab has demonstrated that RGCs carrying mutated Opa1 display excess autophagy, accumulation of autophagosomes in axonal hillocks and mitochondrial depletion along axons, all associated with loss of vision in an ADOA mouse model. Remarkably, genetic inhibition of autophagy restored both axonal mitochondria distribution and vision in ADOA mice. We hence reasoned that pharmacological inhibition of pathways connecting ADOA mitochondria to autophagy hyperactivation could restore axonal mitochondrial distribution in ADOA RGCs, ultimately interrupting the pathogenetic cascade that leads to blindness. To this end, we seek to perform a high content imaging-based drug screening to identify compounds rescuing axonal mitochondrial content in ADOA RGCs. Such large-scale experiment however highlighted the technical bottleneck that is to work with primary mouse RGCs. Indeed, isolating primary RGC from mice cannot provide the sufficient amount of biological material that is necessary. To meet this demand, we have generated the first immortalized RGC line which will also facilitate our in vitro studies overall
C’è mercato per i taxi elettrici in Italia?
Get PDFIl lavoro presenta un modello di Costo Totale di Possesso per valutare la competitività in Italia dei taxi elettrici rispetto ai due sistemi di propulsione maggiormente utilizzati dai tassisti: l’ibrido e il diesel. Stimiamo in particolare il prezzo di listino di break-even, utilizzando dati reali raccolti attraverso interviste ai tassisti fiorentini. Dai nostri risultati emerge come i taxi elettrici
rappresentino già, almeno nelle grandi città, valide alternative ai taxi convenzionali non solo dal punto di vista ambientale ma anche da quello economico. In particolare, anche senza incentivi finanziari e considerando percorrenze annuali facilmente raggiungibili dai tassisti, i taxi elettrici risultano già competitivi rispetto ai diesel e quasi competitivi rispetto agli ibridi. Realizziamo
inoltre analisi di sensitività per testare la sensibilità dei risultati ottenuti alla distanza annuale percorsa, alla quota di viaggi urbani o extraurbani e alle abitudini di ricarica (a casa, o presso stazioni pubbliche, ed in che misura)
Opening the doors to cytochrome c: changes in mitochondrial shape and apoptosis.
No full textMitochondria are key organelles in the regulation of apoptosis induced by intrinsic stimuli. This is accomplished by the release in the cytoplasm of cytochrome c and of other cofactors that ensure the activation of effector caspases. Multiple changes in the shape of the organelle occur around the time of the release of these factors, including fragmentation of the mitochondrial network and the activation of the so-called "cristae remodeling" pathway. However, contrasting evidence exist on the functional role of these changes. Here we review the molecular mechanisms that control mitochondrial shape, their changes during apoptosis and the role that these changes might play in the amplification of the apoptotic cascade
Mobilità attiva prima e durante il Covid-19: il caso studio di Trieste
Get PDFIl contributo indaga la scelta della modalità di trasporto per raggiungere il centro urbano, con un focus sulla città di Trieste. Abbiamo raccolto dati di preferenza rivelata e dichiarata e stimato un modello logit a parametri casuali per individuare le principali determinanti della scelta. Abbiamo inoltre analizzato le abitudini di mobilità dei triestini prima e durante la pandemia da Covid-19. Si conferma che, anche nel caso di Trieste, l’emergenza sanitaria ha alterato in modo significativo le scelte della modalità di trasporto, avendo un forte impatto negativo sull’uso degli autobus e spostando gli utenti verso modalità private, sia motorizzate che non. Abbiamo poi applicato tale modello per valutare l’impatto sulla scelta modale di una maggiore densità di piste ciclabili e/o di una conseguente potenziale riduzione dei tempi di percorrenza. Le nostre stime indicano un potenziale aumento nell’uso della bici (propria e in sharing) che, però, non si tradurrebbe in un corrispondente aumento della quota di mobilità attiva, poiché la bici verrebbe impiegata per sostituire alcuni viaggi attualmente effettuati a piedi. Rileviamo, inoltre, che l’impatto sull’uso dei mezzi motorizzati sarebbe molto limitato, con una riduzione pertanto non significativa della congestione e dell'inquinamento atmosferico e acustico
Cristae Remodeling and Mitochondrial Fragmentation: A Checkpoint for Cytochrome c Release and Apoptosis?
No full textA crucial amplificatory event in several apoptotic cascades is the complete release of cytochrome c from mitochondria. This is accomplished by the activation of multidomain proapoptotic members of the Bcl-2 family and accompanied by changes in the internal structure of mitochondria, a process known as cristae remodelling, and by mitochondrial fragmentation. Here we illustrate the role of dynamin-related proteins controlling mitochondrial morphology in the regulation of cristae remodelling, organelle fragmentation, cytochrome c release, apoptosis and genetic diseases like dominant optic atrophy; and discuss the controversies on their functional role in apoptosis, with an outlook on the possible exploitation of the inhibition of these proteins in cancer chemotherapy
Caspase-8 goes cardiolipin: a new platform to provide mitochondria with microdomains of apoptotic signals?
No full textIn certain cell types, apoptosis in response to extracellular stimuli like Fas depends on a mitochondrial amplificatory loop: the apical caspase-8 cleaves and activates the BH3-only member of the Bcl-2 family BID. In turn, BID induces the release of cytochrome c from mitochondria to the cytoplasm, where it is required to fully activate effector caspases. In this issue of The Journal of Cell Biology, Gonzalvez et al. (see p. 681) show that when caspase-8 activation and production of functional BID is required, it is performed on mitochondrial platforms provided by the mitochondrion-specific lipid cardiolipin. Cardiolipin anchors caspase-8 at contact sites between inner and outer mitochondrial membranes, facilitating its self activation. These findings suggests that like other second messengers such as Ca(2+) and cAMP, production of apoptotic messengers can be compartmentalized in close proximity to their intracellular target
Mitochondrial Apoptosis Regulation by Bcl-2 Family Members
No full textA key ampLificatory mechanism of programmed cell death depends on the release of proapoptotic factors from the mitochondria, crucial organelles in intermediary metaboLism, and energy conversion characterized by a dynamic morphology, ultrastructure, and intracellular locaLization. The proapoptotic factor required for the assembly of the apoptosome and hence for the activation of effector caspases is the only soluble component of the mitochondrial electron transport chain, cytochrome c, whose submitochondrial locaLization is controlled by the organellar shape. Its release across the outer mitochondrial membrane is controlled by the cell death regulator proteins that belong to the family of B cell lymphoma (BCL)-2, the first oncogene to be discovered to function in the regulation of apoptosis. In this article, we will summarize how Bcl-2 family members recruit mitochondria in the apoptotic pathway, by causing their permeabiLization and morphological remodeLing
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