1,720,962 research outputs found
Purinergic signaling and cell proliferation and differentiation in a neuronal pheocromocytoma PC12 cell model
No full textEXPRESSION AND ACTIVITY OF GPR17, A NEW NUCLEOTIDE-CYSTEINYL-LEUKOTRIENE RECEPTOR, IN NEURONAL PC12 CELL MODEL.
No full textNovel classes of potent and selective antagonists at the A1 and A3 adenosine receptors designed by database searching and molecular simplification
No full textPurinergic system: involvement in brain injury and repair
No full textStroke is one of the main cause of death and adult disability in the world, but up to now only limited therapeutically strategies exist. In the last years several studies have been conducted to individuate new potential targets, but none of the trials of drugs can be recommended for use in the regular therapy of cerebral ischemia. In the central nervous system the metabolic stress related to hypoxia, ischemia and trauma elicits large increase in the concentration of nucleotides and adenosine, which has an important role in controlling subsequent tissue damage. In this work two therapeutic strategies for ischemic brain damage involving the purinergic system have been proposed.
Considering the dangerous role of the activation of A3 adenosine receptor in ischemic damage, three classes of heterocyclic ligands were tested at human adenosine receptor subtypes and the best combination of substituentes was found to individuate the most affine and selective antagonists at human A3 adenosine receptor. The most interesting compound from the Pyrido[2,3-e]-1,2,4-triazolo[4,3-a]pyrazin-1-one derivatives was also tested in a rat in vitro model of cerebral ischemia showing an attractive effect on preventing the failure of synaptic activity induced by oxygen glucose deprivation.
An emerging approach to treat the ischemic brain damage is the self brain repair. Given the difficulty to use exogenous stem cells for neuronal restoration, the best strategy could be to induce the self brain repair of damage acting on the activation of neural precursor or potentiating the action of neurotrophic factors. Nucleotides and leukotrienes are to unrelated class of ligands that are both released after a neuronal damage, and several studies have been carried out about the involvement of nucleotides as trophic agents in neuronal survival and neurotigenesis in regenerative conditions. In this work it has been demonstrated that uracil-sugar nucleotides and leukotrienes can improve the action of the nerve growth factors in a cell model of neuronal differentiation (PC12 cells) and so behave as neurotrophic agents. It has been suggested a possible mechanism of these effects, through the activation of the new P2Y- like receptor GPR17 which is a dualistic receptor activated by both uracil nucleotides and cysteinyl leukotrienes
Engineered Kidney Tubules for Modeling Patient-Specific Diseases and Drug Discovery
No full textThe lack of engineering systems able to faithfully reproduce complex kidney structures in vitro has made it difficult to efficiently model kidney diseases and development. Using polydimethylsiloxane (PDMS) scaffolds and a kidney-derived cell line we developed a system to rapidly engineer custom-made 3D tubules with typical renal epithelial properties. This system was successfully employed to engineer patient-specific tubules, to model polycystic kidney disease (PKD) and test drug efficacy, and to identify a potential new pharmacological treatment. By optimizing our system we constructed functional ureteric bud (UB)-like tubules from human induced pluripotent stem cells (iPSCs), and identified a combination of growth factors that induces budding morphogenesis like embryonic kidneys do. Finally, we applied this assay to investigate budding defects in UB-like tubules derived from a patient with a PAX2 mutation.Our system enables the modeling of human kidney disease and development, drug testing and discovery, and lays the groundwork for engineering anatomically correct kidney tissues in vitro and developing personalized medicine applications. Keywords: Tubule engineering, Human pluripotent stem cells, Polycystic kidney disease, Ureteric bud, Drug discovery, PAX
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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