In Vivo Localization of Fas-Associated Death Domain Protein in the Nucleus and Cytoplasm of Normal Thyroid and Liver Cells

FADD (Fas-associated death domain) is the main death receptor adaptor molecule that transmits apoptotic signal. Recently, FADD protein was shown to be expressed both in the cytoplasm and nucleus of in vitro cell lines. In contrast to the cytoplasmic FADD, the nuclear FADD was shown to protect cells from apoptosis. However, in vivo subcellular localization of FADD was still unknown. Here, we demonstrated that FADD protein was expressed in both cytoplasmic and nuclear compartment in ex vivo thyroid cells demonstrating that nuclear sublocalization of FADD protein was a relevant phenomenon occurring in vivo. Moreover, we showed that in the nucleus of untransformed thyroid cells FADD localized mainly on euchromatin. We confirmed the nuclear localization of FADD in ex vivo liver and showed that in this organ FADD and MBD4 interact together. These results demonstrate that FADD is physiologically expressed in the nucleus of cells in at least two mouse organs. This particular localization opens new possible role of FADD in vivo either asan inhibitor of cell death, or as a transcription factor, or as a molecular link between apoptosis and genome surveillance

SEEDS - THE INTERNATIONAL MASTER PROGRAM FOR PREPARING THE YOUNG SYSTEMS ENGINEERS FOR SPACE EXPLORATION

The SEEDS initiative originated by Politecnico di Torino and Thales Alenia Space Italy in 2005. It aimed at establishing a Post Graduate International Master Course in Space Exploration and Development Systems "SEEDS", to offer an opportunity to young engineers to get prepared for the future of Europe in space exploration. The SEEDS project has been shared with Supaero Toulouse in France and with University at Bremen (together with ZARM) in Germany, as the three European towns (Torino, Toulouse and Bremen) have a long common tradition of space activities at both the industrial and academic level and represent three poles of the European cooperation in space programs. The SEEDS course comprises two different steps in sequence: an initial Learning Phase and a Project Work Phase. Both the Learning and the Project Work Phase pursue a multidisciplinary approach, where all specialized disciplines are blended together and integrated to enable the students to acquire the system view and then to accomplish the conceptual design, through the Systems Engineering approach, of a selected case-study. The distinguishing feature of SEEDS is without any doubt the Project Work activity, performed by all students together under the supervision of academic and industrial Tutors, coordinated by the Education Project Manager. Main objective of the Project Work is to train the students on the basic principles of the System Engineering Design, through their application on a well defined project related to a specific space exploration mission. The Project Work includes the Preparatory Work, during which the students, starting from the definition of the mission statement, focus on the identification of the complete architecture of the space exploration mission, and the Conceptual Design activities, performed in the three European sites to develop a limited number of building blocks identified during the Preparatory Work. The first year of activity started in November 2005, with a Plenary Opening which took place at the ESA-ERASMUS Centre, Noordwijk, with the full support of the Human Space-Flight Microgravity and Exploration Directorate of ESA. Five years of activities have passed since then and five project works have been successfully completed, dealing with various space exploration themes. This paper focuses on the description of the SEEDS course and on the main results achieved in terms of project work activities and development of the future space workforce. The positive experience of five years of SEEDS is brought to evidence and the lessons learned are discussed in view of the SEEDS continuatio

Termofluidodinamica (II edizione ampliata)

Questo testo, nella sua seconda edizione ampliata e rivista, è destinato agli studenti dei Corsi di Laurea in Ingegneria previsti dai nuovi ordinamenti degli studi ed in particolare di quelli in Ingegneria Aerospaziale. Esso si propone come tramite tra le nozioni fondamentali di termodinamica impartite nei corsi di fisica di base e le leggi generali del moto dei fluidi in vista delle applicazioni che saranno oggetto degli insegnamenti successivi

Termofluidodinamica (II edizione ampliata)

Questo testo, nella sua seconda edizione ampliata e rivista, è destinato agli studenti dei Corsi di Laurea in Ingegneria previsti dai nuovi ordinamenti degli studi ed in particolare di quelli in Ingegneria Aerospaziale. Esso si propone come tramite tra le nozioni fondamentali di termodinamica impartite nei corsi di fisica di base e le leggi generali del moto dei fluidi in vista delle applicazioni che saranno oggetto degli insegnamenti successiv

Estimating and visualising the trade-off between benefits and harms on multiple clinical outcomes in network meta-analysis.

BACKGROUND The relative treatment effects estimated from network meta-analysis can be employed to rank treatments from the most preferable to the least preferable option. These treatment hierarchies are typically based on ranking metrics calculated from a single outcome. Some approaches have been proposed in the literature to account for multiple outcomes and individual preferences, such as the coverage area inside a spie chart, that, however, does not account for a trade-off between efficacy and safety outcomes. We present the net-benefit standardised area within a spie chart, [Formula: see text] to explore the changes in treatment performance with different trade-offs between benefits and harms, according to a particular set of preferences. METHODS We combine the standardised areas within spie charts for efficacy and safety/acceptability outcomes with a value λ specifying the trade-off between benefits and harms. We derive absolute probabilities and convert outcomes on a scale between 0 and 1 for inclusion in the spie chart. RESULTS We illustrate how the treatments in three published network meta-analyses perform as the trade-off λ varies. The decrease of the [Formula: see text] quantity appears more pronounced for some drugs, e.g. haloperidol. Changes in treatment performance seem more frequent when SUCRA is employed as outcome measures in the spie charts. CONCLUSIONS [Formula: see text] should not be interpreted as a ranking metric but it is a simple approach that could help identify which treatment is preferable when multiple outcomes are of interest and trading-off between benefits and harms is important

Targeting CD226/DNAX accessory molecule-1 (DNAM-1) in collagen-induced arthritis mouse models

International audienceBackground: Genetic studies have pointed out that CD226 variants, encoding DNAM-1, could be associated with susceptibility to rheumatoid arthritis. Therefore, we aimed to determine the influence of DNAM-1 on the development of arthritis using the collagen-induced arthritis (CIA) mouse model. Methods: CIA was induced in mice on a DBA/1 background, treated in parallel with a DNAM-1 neutralizing monoclonal antibody, a control IgG and PBS, respectively. CIA was also induced in mice deficient for DNAM-1(dnam1−/−) and control dnam-1+/+ mice on a C57/BL6 background. Mice were monitored for clinical and ultrasound signs of arthritis. Histological analysis was performed to search for inflammatory infiltrates and erosions. The Mann–Whitney U test for non-related samples was used for statistical analysis. Results: There was a non-significant trend for a less arthritic phenotype in mice receiving anti-DNAM-1 mAb at both clinical, ultrasound and histological assessments. But, we did not observe any difference between dnam1+/+ and dnam1−/− mice for incidence nor severity of clinical arthritis. Histological analysis revealed inflammatory scores similar in both groups, without evidence of erosion. Collagen antibodies levels were similar in all mice, confirming immunization with collagen. Conclusion: Despite some clues suggesting a role of DNAM-1 in arthritis, these complementary approaches demonstrate no contribution of CD226/DNAM-1 in the arthritic phenotype. These results contrast with previous studies showing a role in vivo of DNAM-1 in some autoimmune disorders