15 research outputs found

    Arhitektonska dekoracija Augusteuma iz Narone

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    U tekstu je obrađena arhitektonska dekoracija Augusteuma iz Narone u odnosu na dosad poznatu rimsku arhitektonsku dekoraciju. Datirana je u srednje Augustovo doba

    Heparin Protects Human Neural Progenitor Cells from Zika Virus-Induced Cell Death While Preserving Their Differentiation into Mature Neuroglial Cells

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    Zika virus (ZIKV) is an arbovirus member of the Flaviviridae family that causes severe congenital brain anomalies in infected fetuses. The key target cells of ZIKV infection, human neural progenitor cells (hNPCs), are highly permissive to infection that causes the inhibition of cell proliferation and induces cell death. We have previously shown that pharmaceutical-grade heparin inhibits virus-induced cell death with negligible effects on in vitro virus replication in ZIKV-infected hNPCs at the "high" multiplicity of infection (MOI) of 1. Here, we show that heparin inhibits formation of ZIKV-induced intracellular vacuoles, a signature of paraptosis, and inhibits necrosis and apoptosis of hNPCs grown as neurospheres (NS). To test whether heparin preserved the differentiation of ZIKV-infected hNPCs into neuroglial cells, hNPCs were infected at the MOI of 0.001. In this experimental condition, heparin inhibited ZIKV replication by ca. 2 log10, mostly interfering with virion attachment, while maintaining its protective effect against ZIKV-induced cytopathicity. Heparin preserved differentiation into neuroglial cells of hNPCs that were obtained from either human-induced pluripotent stem cells (hiPSC) or by fetal tissue. Quite surprisingly, multiple additions of heparin to hNPCs enabled prolonged virus replication while preventing virus-induced cytopathicity. Collectively, these results highlight the potential neuroprotective effect of heparin that could serve as a lead compound to develop novel agents for preventing the damage of ZIKV infection on the developing brain. IMPORTANCE ZIKV is a neurotropic virus that invades neural progenitor cells (NPCs), causing inhibition of their proliferation and maturation into neurons and glial cells. We have shown previously that heparin, an anticoagulant also used widely during pregnancy, prevents ZIKV-induced cell death with negligible inhibition of virus replication. Here, we demonstrate that heparin also exerts antiviral activity against ZIKV replication using a much lower infectious inoculum. Moreover, heparin interferes with different modalities of virus-induced cell death. Finally, heparin-induced prevention of virus-induced NPC death allows their differentiation into neuroglial cells despite the intracellular accumulation of virions. These results highlight the potential use of heparin, or pharmacological agents derived from it, in pregnant women to prevent the devastating effects of ZIKV infection on the developing brain of their fetuses

    Gli edifici ecclesiastici di Phoinike e del suo territorio tra tarda Antichit\ue0 e Medioevo

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    Last season of excavation in Phoinike (Albania) helped to better define the chronology and plan of the late antique basilica inserted in a wider Bishop complex. In the meantime a new ecclesiastical building was found on the top of the hill close to the \u2018Laurus Nobilis\u2019. This church was built during the 7th c. and abandoned in the late 15th century, when the city of Phonike was already controlled by the Sultan of Epirus. It is a church square with a central apse and three small aisles, preceded by a rectangular vestibule. In the second phase, the building was restricted to two aisles. Around the ecclesiastical complex was settled a large cemetery. Some architectural elements, found in the collapsing layers, show an interior decoration made up of limestone capitals and pulvini sculpted by local craftsman. The church sets and reuses the structures of an imposing Sto\ue0, located in one of the most prestigious areas of the city. In this paper we will try to frame the phenomenon of transformation of Albanian cities in an attempt to verify the data collected at Phoinike in a wider regional context, both in terms of new religious structures and other aspects of medieval topography

    Territory, city, and private life at <i>Suasa</i>

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    L'Augusteum di Fanum Fortunae. Un edificio del culto imperiale nella Fano d'et\ue0 romana

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    Il libro riassume le ricerche, avviate nel 1899 e riprese nel 2006, sul sito di un importante quartiere della citt\ue0 romana di Fano. Per lungo tempo le scoperte avvenute in occasione della costruzione di un edificio scolastico furono mal comprese e interpretate erroneamente come un edificio termale. Il riesame di tutta la documentazione e le interpretazioni inedite che ne sono consegiite sono raccolte nei nove capitoli del libro, tre dei quali, oltre alla prefazione, scritti dal curatore. Il rilevante complesso archeologico esaminato si rivela comprendere un importante edificio sacro destinato al culto imperiale, dell'et\ue0 di Claudio. Sono proposte alcune importanti ricostruzioni dell'edificio e dei suoi rivestimenti pavimentali e parietali. Si presenta anche tutto il materiale recuparato nel corso dei recenti scavi stratigrafici, che hanno permesso una precisa cronologia dell'edifico attorno al 45 d.C. Viene anche riesaminato il corredo figurativo superstite, comprendete fra l'altro una statua dell'imperatore Claudio e quella del suo figlio giovinetto Britannico

    A Defective Circulating Mitochondrial Bioenergetics Profile Reflects the Hepatic One and Outlines Genetic MASLD

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    Genetics and mitochondrial (mt) dysfunction contribute to metabolic dysfunction-associated steatotic liver disease (MASLD). Recently, we demonstrated that the co-presence of PNPLA3, TM6SF2 and MBOAT7 polymorphisms predisposes to disease progression in MASLD patients and that their deletion triggers mt maladaptation in vitro. Here, we deepened the impact of the silencing of these genes on mt dynamism and respiration by reintroducing TM6SF2 and/or MBOAT7 wild-type proteins in deleted cells through lentiviral infection. Since hepatic mt bioenergetics is impaired in MASLD, in the attempt to identify a non-invasive signature, we then compared the enzymatic mt activity of seahorses, which was assessed in liver biopsies and peripheral blood mononuclear cells (PBMCs) of biopsy-proven MASLD patients (n = 44; Discovery cohort) stratified according to the number of the three at-risk variants (3NRV). Concerning the in vitro results, the rescue of MBOAT7 and/or TM6SF2 wild-type proteins resulted in the assembly of spaghetti-shaped mitochondria with improved oxidative phosphorylation (OXPHOS) capacity. In the Discovery cohort, the hepatic bioenergetic profile fully reflected that in PBMCs and was impaired especially in 3NRV carriers. A lowered serum respiration rate was confirmed in noninvasively assessed MASLD (n = 45; Fibroscan-MASLD cohort), while it did not change in unrelated liver disease patients (n = 45). In summary, we firstly demonstrated that mt circulating respirometry reflects that in liver and is specific in defining genetic MASLD

    Heparin protects human neural progenitor cells from Zika Virus-induced cell death and preserves their differentiation into mature neural-glia cells

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    AbstractZika virus (ZIKV) is an arbovirus member of the Flaviviridae family that causes severe congenital brain anomalies in infected fetuses. Human neural progenitor cells (hNPCs) are highly permissive to ZIKV infection, causing inhibition of cell proliferation concomitant with an induction of cell death. We previously demonstrated that pharmaceutical-grade heparin inhibited virus-induced cell death with minor effects on in vitro virus replication in ZIKV-infected hNPCs. Here we show that heparin prevented ZIKV-induced intracellular vacuoles, a signature characteristic of paraptosis, but also inhibited necrosis and apoptosis of hNPCs when grown as neurospheres (NS). Furthermore, heparin preserved the differentiation of both ZIKV-infected human-induced pluripotent stem cells (hiPSC) derived-NPCs and fetus-derived NPCs into neural-glial cells. Collectively, these results highlight the potential neuroprotective effect of heparin that could be re-purposed and exploited to drive the development of novel agents for preventing ZIKV damage.</jats:p

    La consulenza immobiliare nel private banking

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    Che agli italiani piaccia investire nel mattone non è una novità. Anzi, la proprietà immobiliare è un obiettivo di investimento parallelo se non precedente a quello finanziario. Ciò che invece manca è una vera offerta di servizi di real estate advisory, che consenta di sfruttare tutte le potenzialità del patrimonio immobiliare. Il libro illustra le opportunità connesse allo sviluppo di questo tipo di consulenza, analizza le principali tematiche e i fattori che causano una inefficiente o non oculata gestione degli immobili, erodendo una componente significativa del rendimento rispetto alle vaste possibilità di ottimizzazione che un approccio fornito da attori qualificati consentirebb
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