1,721,066 research outputs found
De novo mammalian prion synthesis
No full textPrions are responsible for a heterogeneous group of fatal neurodegenerative diseases. They can be sporadic, genetic, or infectious disorders involving post-translational modifications of the cellular prion protein (PrP(C)). Prions (PrP(Sc)) are characterized by their infectious property and intrinsic ability to convert the physiological PrP(C) into the pathological form, acting as a template. The "protein-only" hypothesis, postulated by Stanley B. Prusiner, implies the possibility to generate de novo prions in vivo and in vitro. Here we describe major milestones towards proving this hypothesis, taking into account physiological environment/s, biochemical properties and interactors of the PrP(C)
Gene expression profiling and therapeutic interventions in neurodegenerative diseases: a comprehensive study on potentiality and limits
No full textNeurodegenerative diseases are incurable debilitating disorders of the nervous system that affect approximately 30 million people worldwide. Despite profuse efforts attempting to define the molecular mechanisms underlying neurodegeneration, many aspects of these pathologies remain elusive. The novelty of their mechanisms represents a challenge to biology, to their related biomarkers identification and drug discovery. Because of their multifactorial aspects and complexity, gene expression analysis plat- forms have been extensively used to investigate altered pathways during degeneration and to identify potential biomarkers and drug targets
Il sistema culturale: offerta, consumo, politiche
No full textThis paper is organized in two parts: the first represents a synthetic mapping of the current cultural
offer within Provincia di Trento. existing institution operating in the cultural field have therefore been
tracked, and sorted out depending from their field of activity (museums, ecomuseums, natural parks,
other organizations). Relations among organizations and institutions involved have been tracked as
well. Monographic XX in attachment for each institution involved complete the paper. The second part
analyses local cultural policies, starting from an historical overview, and going then in depth with the
specific issue of cultural policies arisen in this context
Gene expression profiling to identify druggable targets in prion diseases
No full textImportance of the field: Despite many recent advances in prion research, the
molecular mechanisms by which prions cause neurodegeneration have not
been established. In fact, the complexity and the novelty characterizing this
class of disorders pose a huge challenge to drug discovery. Pharmacogenomics
has recently adopted high-throughput transcriptome analyses to predict
potential drug target candidates, with promising results in various fields
of medicine.
Areas covered in this review: The present work offers an overview of the
transcriptional alterations induced by prion infection in different biological
systems. Hereafter, therapeutic approaches are discussed in light of the
identified altered processes.
What the reader will gain: This review offers readers a detailed overview on
microarray analyses, taking into account their advantages and limitations.
Our work can help readers, from many research areas, to design a suitable
microarray experiment.
Take home message: So far, drugs acting on the pathways identified by
microarray analysis have not been found to be effective in prion diseases
therapy. An integration of gene expression profiling, proteomics and
physiology should be applied to pursue this aim
The role of Bax and caspase-3 in doppel-induced apoptosis of cerebellar granule cells
No full textDoppel (Dpl) protein is a paralog of the prion protein (PrP) that shares 25% sequence similarity with the C-terminus of PrP, a common N-glycosylation site and a C-terminal signal peptide for attachment of a glycosylphophatidyl inositol anchor. Whereas PrPC is highly expressed in the central nervous system (CNS), Dpl is detected mostly in testes and its ectopic expression in the CNS leads to ataxia as well as Purkinje and granule cell degeneration in the cerebellum. The mechanism through which Dpl induces neurotoxicity is still debated. In the present work, primary neuronal cultures derived from postnatal cerebellar granule cells of wild-type and PrP-knockout FVB mice were used in order to investigate the molecular events that occur upon exposure to Dpl. Treatment of cultured cerebellar neurons with recombinant Dpl produced apoptosis that could be prevented by PrP co-incubation. When primary neuronal cultures from Bax-deficient mice were incubated with Dpl, no apoptosis was observed, suggesting an important role of Bax in triggering neurodegeneration. Similarly, cell survival increased when recDpl-treated cells were incubated with an inhibitor of caspase-3, which mediates apoptosis in mammalian cells. Together, our findings raise the possibility that Bax and caspase-3 feature in Dpl-mediated apoptosis
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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