67 research outputs found

    RiboAbacus: a model trained on polyribosome images predicts ribosome density and translational efficiency from mammalian transcriptomes

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    Fluctuations in mRNA levels only partially contribute to determine variations in mRNA availability for translation, producing the well-known poor correlation between transcriptome and proteome data. Recent advances in microscopy now enable researchers to obtain high resolution images of ribosomes on transcripts, providing precious snapshots of translation in vivo. Here we propose RiboAbacus, a mathematical model that for the first time incorporates imaging data in a predictive model of transcript-specific ribosome densities and translational efficiencies. RiboAbacus uses a mechanistic model of ribosome dynamics, enabling the quantification of the relative importance of different features (such as codon usage and the 5′ ramp effect) in determining the accuracy of predictions. The model has been optimized in the human Hek-293 cell line to fit thousands of images of human polysomes obtained by atomic force microscopy, from which we could get a reference distribution of the number of ribosomes per mRNA with unmatched resolution. After validation, we applied RiboAbacus to three case studies of known transcriptome-proteome datasets for estimating the translational efficiencies, resulting in an increased correlation with corresponding proteomes. RiboAbacus is an intuitive tool that allows an immediate estimation of crucial translation properties for entire transcriptomes, based on easily obtainable transcript expression levels

    Transcriptional Control of Steroid Biosynthesis Genes in the Drosophila Prothoracic Gland by Ventral Veins Lacking and Knirps.

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    Specialized endocrine cells produce and release steroid hormones that govern development, metabolism and reproduction. In order to synthesize steroids, all the genes in the biosynthetic pathway must be coordinately turned on in steroidogenic cells. In Drosophila, the steroid producing endocrine cells are located in the prothoracic gland (PG) that releases the steroid hormone ecdysone. The transcriptional regulatory network that specifies the unique PG specific expression pattern of the ecdysone biosynthetic genes remains unknown. Here, we show that two transcription factors, the POU-domain Ventral veins lacking (Vvl) and the nuclear receptor Knirps (Kni), have essential roles in the PG during larval development. Vvl is highly expressed in the PG during embryogenesis and is enriched in the gland during larval development, suggesting that Vvl might function as a master transcriptional regulator in this tissue. Vvl and Kni bind to PG specific cis-regulatory elements that are required for expression of the ecdysone biosynthetic genes. Knock down of either vvl or kni in the PG results in a larval developmental arrest due to failure in ecdysone production. Furthermore, Vvl and Kni are also required for maintenance of TOR/S6K and prothoracicotropic hormone (PTTH) signaling in the PG, two major pathways that control ecdysone biosynthesis and PG cell growth. We also show that the transcriptional regulator, Molting defective (Mld), controls early biosynthetic pathway steps. Our data show that Vvl and Kni directly regulate ecdysone biosynthesis by transcriptional control of biosynthetic gene expression and indirectly by affecting PTTH and TOR/S6K signaling. This provides new insight into the regulatory network of transcription factors involved in the coordinated regulation of steroidogenic cell specific transcription, and identifies a new function of Vvl and Knirps in endocrine cells during post-embryonic development

    In malga: indagine in quattro aree delle Alpi Centrali sugli atteggiamenti dei turisti-escursionisti riguardo agli alpeggi

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    This paper discusses the results of a survey carried out in the summer of 2003 with the aim of gaining a deeper understanding of the attitudes of contemporary tourists towards mountain pastures. 829 visitors were interviewed in four areas in the provinces of Bergamo, Sondrio and Trento using a brief questionnaire. Besides enabling us to gather information about the basic demographic features of the tourist, the questions focused on the motivations for the visit and the attitudes towards specific aspects of pasture land such as landscape, grazing animals and local produce. The tourist profile which emerged from the bivariate analysis ascribed major relevance to the culture and environment associated with mountain pastures rather than the functional meanings. The age of the interviewees was the most significant variable in discriminating the answers: older people tended to appreciate the various different aspects to a greater extent

    Sensibilit\ue0 Chimica Multipla (SCM): componenti psicologiche nell'evoluzione del disturbo.

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    Introduzione. La Sensibilit\ue0 Chimica Multipla (SCM) \ue8 una malattia dall\u2019eziologia ancora ignota, caratterizzata da sintomi attribuibili a un\u2019intolleranza per agenti chimici presenti nell\u2019ambiente, in assenza di altre spiegazioni mediche. Nonostante la patogenesi della malattia sia ancora incert,a sono stati chiamati in causa fattori sia psicologici, sia fisici per spiegarne le cause. Il presente studio qualitativo ha lo scopo di riportare le opinioni, le credenze e il modo di raccontare la malattia in pazienti affetti da MCS. Metodo. Hanno partecipato allo studio 40 soggetti, lamentanti sintomi riconducibili alla MCS, di et\ue0 compresa tra i 32 e i 78 anni. Tutti i soggetti hanno partecipato a un colloquio clinico guidato da intervista semi strutturata. Risultati. I sontomi maggiormente riportati dai partecipanti sono: ipersensibilit\ue0 olfattiva a sostanze chimiche, nausea, mal di testa, mancanza di concentrazione, difficolt\ue0 mnestiche. I pazienti riferiscono una bassa qualit\ue0 di vita, depressione, ansia ed episodi di attacco di panico. Conclusioni. Questo studio evidenzia la cronicit\ue0 e la condizione disabilitante in cui si trovano i pazienti con MCS e sottolinea l\u2019importanza di lavorare per il miglioramento della loro qualit\ue0 di vita.Comprendere l\u2019impatto della malattia sulla salute globale dei soggetti \ue9 fondamentale per comprendere e trattare le persone con MCS
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