1,721,009 research outputs found
Dopamine-depletion and increased alpha-synuclein load induce degeneration of cortical cholinergic fibers in mice
No full textCognitive dysfunction can be common among Parkinson's disease (PD) patients, and multiplication of the gene alpha-synuclein (alpha syn) increases the risk of dementia. Here, we studied the role of dopamine-depletion and increased asyn load and aggregation on cholinergic structures in vivo. Wild-type (WT) and mice with A30P asyn overexpression were treated subacutely with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MFTP), and the number of cholinergic cells in their nucleus basalis magnocellularis-substantia innominata (NBM-SI), their cortical fiber density and their expression of different genes 1 day or 90 days after the last MPTP-injection were measured. Long-term dopamine depletion decreased the expression of choline acetyl transferase (ChAT) in the NBM-SI of WT mice, but no neuron loss was observed. In contrast, cortical cholinergic fiber density was decreased three months after MPTP-injection. Increased brain-derived neurotrophic factor expression could maintain cholinergic functions under these conditions. Expression of A30P alpha syn in six-months-old transgenic mice resulted in decreased tyrosine receptor kinase B expression, and lower cortical cholinergic fiber density. Dopamine-depletion by MPTP induced cholinergic cell loss in the NBM-SI and increased cortical fiber loss. Our findings may explain why cholinergic cells are more vulnerable in PD, leading to an increased probability of dementia. (C) 2011 Elsevier B.V. All rights reserved
A30P alpha-synuclein impairs dopaminergic fiber regeneration and interacts with L-DOPA replacement in MPTP-treated mice
No full textParkinson's disease (PD) is the most common neurodegenerative movement disorder and is characterized by the loss of dopaminergic neurons from the substantia nigra pars compacta (SNpc). alpha-synuclein (alpha syn) has been linked to the pathophysiology of PD, because of its mutations causing familial PD and its accumulation in brains of patients with familial and sporadic PD. Dopamine (DA) replacement is the most effective therapy for ameliorating the motor symptoms of PD; however, it remains controversial whether DA-replacement boosts regeneration in the dopaminergic system or accelerates disease progression and enhances neuronal loss. Here, we studied the effect of chronic L-DOPA treatment on dopaminergic neurons in wild-type (WT) and A30P alpha syn transgenic mice after MPTP treatment. Acute MPTP intoxication induced degeneration of dopaminergic neurons in both WT and A30P alpha syn transgenic mice. A strong regeneration of dopaminergic fibers at 90 days after MPTP was observed in WT mice. In contrast, regeneration was less pronounced in A30P alpha syn mice. Chronic L-DOPA treatment after MPTP intoxication did not only reduce the regeneration of nigrostriatal fibers but also led to an increased apoptotic gene-expression profile in the SNpc and to a decline of TH-positive neurons in A30P alpha syn. Our findings reveal that the presence of A30P alpha syn inhibits the regeneration of nigrostriatal dopaminergic fibers, and that L-DOPA treatment might interact with the pathogenesis in PD. (C) 2011 Elsevier Inc. All rights reserved
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
Non-SUMOylated alternative spliced isoforms of alpha-synuclein are more aggregation-prone and toxic
No full textDispelling 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
Sirtuin 2 enhances dopaminergic differentiation via the AKT/GSK-3β/β-catenin pathway
No full text\ua9 2017 Elsevier Inc. Proper and efficient differentiation of dopaminergic (DA) neurons is essential for the cell-based dopamine replacement strategies that have become an attractive therapeutical option in Parkinson\u27s disease, a disorder typically known for the degeneration of the nigral DA neurons. Here, we established that the nicotinamide adenine dinucleotide-dependent deacetylase sirtuin 2 (SIRT2) interacts with protein kinase B, and, via the glycogen synthase kinase 3β/β-catenin pathway, modulates the differentiation of DA neurons. Deletion of SIRT2 resulted in a decreased number of DA neurons in the substantia nigra and lower striatal fiber density in SIRT2 knock-out mice. Similarly, we found a decreased ratio of DA neurons in primary midbrain cultures treated with the SIRT2 inhibitor AK-7. Using protein kinase B and glycogen synthase kinase 3β inhibitors, we found that those molecules act downstream of SIRT2. Thus, SIRT2 acts as a novel regulator of the differentiation process of DA neurons, further supporting its potential as a therapeutic target in Parkinson\u27s disease
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