Estrous cycle-dependent changes of Fas expression in the bovine corpus luteum: influence of keratin 8/18 intermediate filaments and cytokines

Background Fas expression and Fas-induced apoptosis are mechanisms attributed to the selective destruction of cells of the corpus luteum (CL) during luteal regression. In certain cell-types, sensitivity to these death-inducing mechanisms is due to the loss or cleavage of keratin-containing intermediate filaments. Specifically, keratin 8/18 (K8/K18) filaments are hypothesized to influence cell death in part by regulating Fas expression at the cell surface. Methods Here, Fas expression on bovine luteal cells was quantified by flow cytometry during the early (Day 5, postovulation) and late stages (Days 16–18, postovulation) of CL function, and the relationship between Fas expression, K8/K18 filament expression and cytokine-induced cell death in vitro was evaluated. Results Both total and cell surface expression of Fas on luteal cells was greater for early versus late stage bovine CL (89% vs. 44% of cells for total Fas; 65% vs.18% of cells for cell surface Fas; respectively, P0.05, n=4 CL/stage), despite evidence these conditions increased Fas expression on HepG2 cells (P0.05) or stage of CL (P\u3e0.05, n= 4 CL/stage) on this outcome. Conclusion In conclusion, we rejected our null hypothesis that the cell surface expression of Fas does not differ between luteal cells of early and late stage CL. The results also did not support the idea that K8/K18 filaments influence the expression of Fas on the surface of bovine luteal cells. Potential downstream effects of these filaments on death signaling, however, remain a possibility. Importantly, the elevated expression of Fas observed on cells of early stage bovine CL compared to late stage bovine CL raises a provocative question concerning the physiological role(s) of Fas in the corpus luteum, particularly during early luteal development

Nuove procedure per l'assegnazione dei Bandwidth Constraints nei modelli di allocazione MAM, RDM e GRDM

La continua e vertiginosa crescita della rete Internet, la nascita di nuovi tipi di applicazioni che richiedono scambi di dati real-time e la sempre maggiore richiesta di capacità trasmissiva, hanno portato la comunità scientifica sensibile ai problemi dell’Information Technology a sviluppare nuovi metodi per una gestione più efficace delle risorse di rete a disposizione, per una differenziazione del traffico ed un’aderenza sempre maggiore alle esigenze dei client e dei provider. Due delle tecnologie proposte in questi ultimi anni sono state MPLS e DiffServ. MPLS fornisce un’infrastruttura di rete sulla quale è possibile inserire un routing più veloce e scalabile, che tiene conto dello stato della rete e che permette l’impiego di circuiti virtuali lungo cui instradare il traffico. DiffServ è invece un’architettura in grado di fornire servizi e trattamenti diversi ai pacchetti, operando una differenziazione all’interno delle code dei singoli router ed avendo come obiettivo principale quello di fornire supporto e gestione della qualità del servizio. Queste due tecnologie si sono poi rivelate compatibili l’una con l’altra, avendo molti punti in comune e obiettivi non troppo dissimili e congiuntamente raggiungibili; insieme, infatti, hanno dato vita ad un’architettura in grado di gestire le più disparate problematiche relative alla qualità del servizio. Inoltre, si è cominciato ad impiegare le tecniche teoriche di gestione del traffico, dette di Ingegneria del Traffico, e ad integrarle insieme ad MPLS e DiffServ: dall’insieme di queste innovazioni è nata l’architettura DiffServ – Aware MPLS Traffic Engeneering (DS-TE). Per valutare le prestazioni dell’architettura MPLS sono molto utili i simulatori, in quanto, ad oggi, non esistono implementazioni di tale tecnologia su larga scala sulle quali sia possibile effettuare misure in condizioni di traffico reale. Proseguendo il lavoro del Dipartimento di Ingegneria dell’ Informazione dell’Università di Pisa, durante questo lavoro di tesi, si è cercato di studiare delle nuove procedure in grado di migliorare e standardizzare un particolare aspetto del DS-TE, ossia la scelta adeguata dei Bandwidth Constraints, parametri decisivi nella nuova architettura per una gestione intelligente delle risorse di rete

Increased circulating levels of interleukin-6 induce perturbation in redox-regulated signaling cascades in muscle of dystrophic mice

Duchenne muscular dystrophy (DMD) is an X-linked genetic disease in which dystrophin gene is mutated, resulting in dysfunctional or absent dystrophin protein. The pathology of dystrophic muscle includes degeneration, necrosis with inflammatory cell invasion, regeneration, and fibrous and fatty changes. Nevertheless, the mechanisms by which the absence of dystrophin leads to muscle degeneration remain to be fully elucidated. An imbalance between oxidant and antioxidant systems has been proposed as a secondary effect of DMD. However, the significance and precise extent of the perturbation in redox signaling cascades is poorly understood. We report that mdx dystrophic mice are able to activate a compensatory antioxidant response at the presymptomatic stage of the disease. In contrast, increased circulating levels of IL-6 perturb the redox signaling cascade, even prior to the necrotic stage, leading to severe features and progressive nature of muscular dystrophy

MicroRNAs modulated by local mIGF-1 expression in mdx dystrophic mice

Duchenne muscular dystrophy (DMD) is a X-linked genetic disease in which the absence of dystrophin leads to progressive lethal skeletal muscle degeneration. It has been demonstrated that among genes which are important for proper muscle development and function, micro-RNAs (miRNAs) play a crucial role. Moreover, altered levels of miRNAs were found in several muscular disorders, including DMD. A specific group of miRNAs, whose expression depends on dystrophin levels and whose deregulation explains several DMD pathogenetic traits, has been identified. Here, we addressed whether the anabolic activity of mIGF-1 on dystrophic muscle is associated with modulation of microRNAs expression. We demonstrated that some microRNAs are strictly linked to the dystrophin expression and are not modulated by mIGF-1 expression. In contrast, local expression of mIGF-1 promotes the modulation of other microRNAs, such as miR-206 and miR-24, along with the modulation of muscle specific genes, which are associated with maturation of regenerating fibers and with the stabilization of the differentiated muscle phenotype. These data suggest that mIGF-1, modifying the expression of some of the active players of muscle homeostasis, is able, even in absence of dystrophin expression, to activate circuitries that confer robustness to dystrophic muscle