2,015 research outputs found

    Regulation mechanisms of human D-amino acid oxidase

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    The human peroxisomal FAD-dependent enzyme D-amino acid oxidase (hDAAO, EC 1.4.3.3) plays a key role in important physiological processes by catalyzing the stereospecific degradation of several D-amino acids (D-AAs). A number of studies demonstrated that a dysregulation in processes regulating D-AAs concentration is related to the mechanism(s) predisposing to several pathologies. The important role played by hDAAO in modulating D-AAs levels increased the interest for this flavoenzyme: while structural and biochemical properties have been extensively investigated, several aspects in the modulation of its functionality remain elusive. Furthermore, it has been recently suggested that DAAO could be mistargeted to the nucleus or secreted in the (mouse) intestinal lumen, where it could select the composition of gut microbiota by generating H2O2. Here, some biochemical properties of the recombinant enzyme were investigated. Moreover, we focused on mistargeting of DAAO by studying a variant lacking the N-terminal signal peptide (thus shedding light on the mechanism of microbiota selection) and two variants at position 120 (a residue belonging to a putative nuclear translocation signal): the cellular targeting of the flavoenzyme seems a way to modulate hDAAO functionality. This modulation allows hDAAO to fulfil different physiological functions, such as the control of the level of D-Ser in the brain and of other D-AAs in different tissues or the selection of microbiota in the gut

    Negative ion Time Projection Chamber operation with SF6_{6} at nearly atmospheric pressure

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    We present measurements of drift velocities and mobilities of some innovative negative ion gas mixtures at nearly atmospheric pressure based on SF6_{6} as electronegative capture agent and of pure SF6_{6} at various pressures, performed with the NITEC detector. NITEC is a Time Projection Chamber with 5 cm drift distance readout by a GEMPix, a triple thin GEMs coupled to a Quad-Timepix chip, directly sensitive to the deposited charge on each of the 55 ×\times 55 μ\mum2^2 pixel. Our results contribute to expanding the knowledge on the innovative use of SF6_{6} as negative ion gas and extend to triple thin GEMs the possibility of negative ion operation for the first time. Above all, our findings show the feasibility of negative ion operation with He:CF4_4:SF6_{6} at 610 Torr, opening extremely interesting possibility for next generation directional Dark Matter detectors at 1 bar

    The Role of The Ecomuseo Dei Terrazzamenti E Della Vite, (Cortemilia, Italy) in Community Development

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    One important reaction to globalization in the twenty-first century has been the democratization of culture and heritage. Local communities have increasingly attempted to recognise and conserve their heritage resources and use them to create sustainable economic development through ecotourism and cultural tourism. Ecomuseum philosophy and practical processes, although they originated in France, have been used in many countries to enable local residents to define, validate and celebrate local distinctiveness and local identity. This article introduces and critiques these philosophies and processes and then describes how one community in the north of Italy (Cortemilia) used them to harness the natural and cultural resources of its locality to enable local people to re-identify their own ‘sense of place’ and rekindle pride in their community. The conclusion compares the processes and outcomes in Cortemilia with two other ecomuseums created to aid community development

    Possibilità produttive di alcune varietà di soia: risultati di un triennio di esperienze condotte in Sardegna

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    During 1975-76-77, 25 soybeans varieties belonging to different groups of maturity were compared. Experiments - carried out in two different pedoclimatic environments - pointed out the importance of the choice of variety both for production purposes and with reference to harvest time. In the trial carried in the Northern Sardinia, on a calcareous soil, the following varieties showed to be the most productive: «Hodyson» (46.2 q/ha), «Amsoy 71» (45.2 q/ha), «Wells» (43.2 q/ha), « Beeson» (42.9 q/ha), «Corsoy» (42.1 q/ha) and «Williams» (41.5 q/ha). On the contrary, on clayish soils the above varieties were slightly productive, while other ones («Semmes», «Rillito», «Davis»), which gave yields of about 30 q/ha, resulted to be too late. Further trials are required to detect cultivars which, both for the bioiogica1 cycle span and for the yields may be successfully cultivated in southern pedoclimatic environments similar to those where experiments were carried out. Nel corso degli anni 1975-76-77 sono state confrontate 25 varietà di soia appartenenti a differenti classi di maturazione. Le esperienze, condotte in due differenti ambienti pedoclimatici, hanno evidenziato l'importanza della scelta varietale sia ai fini produttivi che con riferimento all'epoca di raccolta. Nella prova condotta nella Sardegna settentrionale, su terreno di origine calcareo, sono risultate più produttive le varietà «Hodgson» (46,2 q/ha), «Amsoy 71» (45,2 q/ha), «Wells» (43,2 q/ha), «Beeson» (42,9 q/ha), «Corsoy» (42,1 q/ha) e «Williams» (41,5 q/ha). Su terreni argillosi dell'Oristanese, invece, le stesse varietà hanno mostrato scarse attitudini produttive, mentre altre («Semmes», «Rillito», «Davis»), che hanno fornito rese intorno a 30 q/ha, sono risultate troppo tardive. Si ritengono pertanto necessarie ulteriori prove agronomiche tendenti all'individuazione di cultivar che, sia per lunghezza del ciclo biologico che per le rese unitarie, possano essere inserite con successo in ambienti pedoclimatici meridionali del tipo di quelli sede delle prove

    Cutaneous Melanoma Classification: The Importance of High-Throughput Genomic Technologies

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    Cutaneous melanoma is an aggressive tumor responsible for 90% of mortality related to skin cancer. In the recent years, the discovery of driving mutations in melanoma has led to better treatment approaches. The last decade has seen a genomic revolution in the field of cancer. Such genomic revolution has led to the production of an unprecedented mole of data. High-throughput genomic technologies have facilitated the genomic, transcriptomic and epigenomic profiling of several cancers, including melanoma. Nevertheless, there are a number of newer genomic technologies that have not yet been employed in large studies. In this article we describe the current classification of cutaneous melanoma, we review the current knowledge of the main genetic alterations of cutaneous melanoma and their related impact on targeted therapies, and we describe the most recent highthroughput genomic technologies, highlighting their advantages and disadvantages. We hope that the current review will also help scientists to identify the most suitable technology to address melanoma-related relevant questions. The translation of this knowledge and all actual advancements into the clinical practice will be helpful in better defining the different molecular subsets of melanoma patients and provide new tools to address relevant questions on disease management. Genomic technologies might indeed allow to better predict the biological - and, subsequently, clinical - behavior for each subset of melanoma patients as well as to even identify all molecular changes in tumor cell populations during disease evolution toward a real achievement of a personalized medicine

    Cutaneous Melanoma Classification: The Importance of High-Throughput Genomic Technologies

    Get PDF
    Cutaneous melanoma is an aggressive tumor responsible for 90% of mortality related to skin cancer. In the recent years, the discovery of driving mutations in melanoma has led to better treatment approaches. The last decade has seen a genomic revolution in the field of cancer. Such genomic revolution has led to the production of an unprecedented mole of data. High-throughput genomic technologies have facilitated the genomic, transcriptomic and epigenomic profiling of several cancers, including melanoma. Nevertheless, there are a number of newer genomic technologies that have not yet been employed in large studies. In this article we describe the current classification of cutaneous melanoma, we review the current knowledge of the main genetic alterations of cutaneous melanoma and their related impact on targeted therapies, and we describe the most recent high-throughput genomic technologies, highlighting their advantages and disadvantages. We hope that the current review will also help scientists to identify the most suitable technology to address melanoma-related relevant questions. The translation of this knowledge and all actual advancements into the clinical practice will be helpful in better defining the different molecular subsets of melanoma patients and provide new tools to address relevant questions on disease management. Genomic technologies might indeed allow to better predict the biological - and, subsequently, clinical - behavior for each subset of melanoma patients as well as to even identify all molecular changes in tumor cell populations during disease evolution toward a real achievement of a personalized medicine
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