1,721,214 research outputs found
Guanine nucleotide depletion induces differentiation and aberrant neurite outgrowth in human dopaminergic neuroblastoma lines: a model for basal ganglia dysfunction in Lesch-Nyhan disease.
No full textLesch-Nyhan disease (LND), caused by complete deficiency of hypoxanthine guanine phosphoribosyltransferase (HPRT), is characterized by a neurological deficit, the etiology of which is unknown. Evidence has accumulated indicating that it might be related to dys A function of the basal ganglia with a prominent loss of striatal dopamine fibers. Guanine nucleoftide depletion has been shown to occur in cells from Lesch-Nyhan patients. In this study we demonstrate that chronic guanine nucleotide depletion induced by inhibition of inosine monophosphate dehydrogenase with low levels (50 nM) of mycophenolic acid (MPA) lead human neuroblastoma cell lines to differentiate toward the neuronal phenotype. The MPA-induced morphological changes were more evident in the dopaminergic line LAN5, than in the cholinergic line IMR32. MPA-induced differentiation, unlike that induced, by retinoic acid, caused a less extensive neurite outgrowth and branching (similar to that observed in cultured HPRT-deficient dopaminergic neurons) and involved up-regulation of p53, p21 and bax, and bcl-2 down-regulation without p27 protein accumulation. These results suggest that guanine nucleotide depletion following HPRT deficiency, might lead to earlier and abnormal brain development mainly affecting the basal ganglia, displaying the highest HPRT activity, and could be responsible for the specific neurobehavioral features of LN
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
Metabolic network of nucleosides in the brain
No full textBrain relies on circulating nucleosides, mainly synthesised de novo in the liver, for the synthesis of nucleotides, RNA, nuclear and mitochondrial DNA, coenzymes, and pyrimidine sugar- and lipid-conjugates. Essentially, the paths of nucleoside salvage in the brain include a two step conversion of inosine and guanosine to IMP and GMP, respectively, and a one step conversion of adenosine, uridine, and cytidine, to AMP, UMP, and CMP, respectively. With the exception of IMP, the other four nucleoside monophosphates are converted to their respective triphosphates via two successive phosphorylation steps. Brain ribonucleotide reductase converts nucleoside diphosphates to their deoxy counterparts. The delicate qualitative and quantitative balance of intracellular brain nucleoside triphosphates is maintained by the relative concentrations of circulating nucleosides, the specificity and the K(m) values of the transport systems and of cytosolic and mitochondrial nucleoside kinases and 5'-nucleotidases, and the relative rates of nucleoside triphosphate extracellular release. A cross talk between extra- and intra-cellular nucleoside metabolism exists, in which released nucleoside triphosphates, utilised as neuroactive signals, are catabolised by a membrane bound ectonucleotidase cascade system to their respective nucleosides, which are uptaken into brain cytosol, and converted back to nucleoside triphosphates by the salvage enzymes. Finally, phosphorolysis of brain nucleosides generates pentose phosphates, which are utilised for nucleoside interconversion, 5-phosphoribosyl-1-pyrophosphate synthesis, and energy repletion. This review focuses on these aspects of brain nucleoside metabolism, with the aim of giving a comprehensive picture of the metabolic network of nucleosides in normoxic conditions, with some hints on the derangements in anoxic/ischemic conditions
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
Pediatric neurological syndromes and inborn errors of purine metabolism
No full textThis review is devised to gather the presently known inborn errors of purine metabolism that manifest neurological pediatric syndromes. The aim is to draw a comprehensive picture of these rare diseases, characterized by unexpected and often devastating neurological symptoms. Although investigated for many years, most purine metabolism disorders associated to psychomotor dysfunctions still hide the molecular link between the metabolic derangement and the neurological manifestations. This basically indicates that many of the actual functions of nucleosides and nucleotides in the development and function of several organs, in particular central nervous system, are still unknown. Both superactivity and deficiency of phosphoribosylpyrophosphate synthetase cause hereditary disorders characterized, in most cases, by neurological impairments. The deficiency of adenylosuccinate lyase and 5-amino-4-imidazolecarboxamide ribotide transformylase/IMP cyclohydrolase, both belonging to the de novo purine synthesis pathway, is also associated to severe neurological manifestations. Among catabolic enzymes, hyperactivity of ectosolic 5'-nucleotidase, as well as deficiency of purine nucleoside phosphorylase and adenosine deaminase also lead to syndromes affecting the central nervous system. The most severe pathologies are associated to the deficiency of the salvage pathway enzymes hypoxanthine-guanine phosphoribosyltransferase and deoxyguanosine kinase: the former due to an unexplained adverse effect exerted on the development and/or differentiation of dopaminergic neurons, the latter due to a clear impairment of mitochondrial functions. The assessment of hypo- or hyperuricemic conditions is suggestive of purine enzyme dysfunctions, but most disorders of purine metabolism may escape the clinical investigation because they are not associated to these metabolic derangements. This review may represent a starting point stimulating both scientists and physicians involved in the study of neurological dysfunctions caused by inborn errors of purine metabolism with the aim to find novel therapeutical approache
Animal and cell models for Lesch-Nyhan syndrome
No full textLesch–Nyhan Disease (LND) is a rare X-linked recessive metabolic and neurological syndrome due to the deficiency of hypoxanthine-guanine phosphoribosyltransferase (HPRT). Peculiar neurological symptoms occur in LND: dystonia, choreoathetosis, compulsive self-injurious behaviour, with no obvious correlation to the deficiency of this purine salvage anzyme. A dopaminergic deficit was found to underlie the neurologic symptoms, but the aetiology for such alteration seemed inexplicable. Several lines of research were carried out to find the molecular basis for the neurological phenotype, and HPRT deficient animal and cellular models were developed. None of them, animal or cellular model, can be considered the completely proper one. Available animal models are rodents, which share several biochemical and molecular abnormalities with HPRT deficient patients, but do not display similar neurologic symptoms. Cellular models obtained from different cell lines present notable biochemical and molecular aberrations though many discrepancies suggest significant differences depending upon cell types and tissue source. Nevertheless, experimental studies on both models provided remarkable information on the biochemical and molecular pathways potentially responsible for the neurological damage in this disease, demonstrating transcriptional aberrations affecting different genes in various metabolic pathways and gene dysregulations in neuronal development and differentiation, producing neurotransmission defects. These findings led to attribute an unexpected paramount role in neurodevelopment to HPRT, beside the well-known metabolic functions.
© 2019 Elsevier Lt
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