187,894 research outputs found
Anti-apoptotic gene therapy in Parkinson's disease
No full textApoptosis, whether caspase-dependent or caspase-independent, has been implicated as one of the important mechanisms leading to the death of dopaminergic neurons in the substantia nigra of Parkinson's disease patients. Major advances of our understanding of apoptosis have been achieved in studies of 1-methyl-4-phenyl-1,2,3,6-tetra-hydropyridine (MPTP) toxicity in mice and monkeys and 6-hydroxydopamine (6-OHDA) toxicity in rats and monkeys. The use of viral vectors to either express anti-apoptotic proteins or to downregulate pro-apoptotic proteins has the major advantage of addressing selective molecular targets, bypassing the blood-brain-barrier to specifically target the nigrostriatal pathway by their stereotaxic application and by the choice of the appropriate virus and promotor. Used thus far have been virus-mediated overexpression of inhibitor of apoptosis proteins, inhibitors of the c-jun-N-terminal kinase (JNK) pathway, inhibitors of calpains and dominant negative inhibitors of the protease activating factor (APAF)-1 and cdk5. Most studies implicate the endogenous, mitochondrial pathway in the apoptosis of dopaminergic neurons. The results suggest that only an inhibition of this pathway upstream of caspase activation will also result in the protection of nigrostriatal dopaminergic terminals and behavioral benefit, whereas an inhibition of caspases alone may not be sufficient to prevent the degeneration of terminals, although it may promote the survival of neuronal cell bodies for some time
Anti-apoptotic gene therapy in Parkinson's disease
No full textApoptosis, whether caspase-dependent or caspase-independent, has been implicated as one of the important mechanisms leading to the death of dopaminergic neurons in the substantia nigra of Parkinson's disease patients. Major advances of our understanding of apoptosis have been achieved in studies of 1-methyl-4-phenyl-1,2,3,6-tetra-hydropyridine (MPTP) toxicity in mice and monkeys and 6-hydroxydopamine (6-OHDA) toxicity in rats and monkeys. The use of viral vectors to either express anti-apoptotic proteins or to downregulate pro-apoptotic proteins has the major advantage of addressing selective molecular targets, bypassing the blood-brain-barrier to specifically target the nigrostriatal pathway by their stereotaxic application and by the choice of the appropriate virus and promotor. Used thus far have been virus-mediated overexpression of inhibitor of apoptosis proteins, inhibitors of the c-jun-N-terminal kinase (JNK) pathway, inhibitors of calpains and dominant negative inhibitors of the protease activating factor (APAF)-1 and cdk5. Most studies implicate the endogenous, mitochondrial pathway in the apoptosis of dopaminergic neurons. The results suggest that only an inhibition of this pathway upstream of caspase activation will also result in the protection of nigrostriatal dopaminergic terminals and behavioral benefit, whereas an inhibition of caspases alone may not be sufficient to prevent the degeneration of terminals, although it may promote the survival of neuronal cell bodies for some time
Limitations of cellular models in Parkinson's disease research
No full textCell cultures for Parkinson's disease research have the advantage of virtually unlimited access, they allow rapid screening for disease pathogenesis and drug candidates, and they restrict the necessary number of animal experiments. Limitations of cell cultures, include that the survival of neurons is dependent upon the culture conditions; that the cells do not develop their natural neuronal networks. In most cases, neurons are deprived from the physiological afferent and efferent connections. In Parkinson's disease research, mesencephalic slice cultures, primary immature doparninergic neurons and immortalized cell lines - either in a proliferating state or in a differentiated state - are used. Neuronal cultures may be plated in the presence or absence of glial cells and serum. These different culture conditions as well as the selection of outcome parameters (morphological evaluation, viability assays, biochemical assays, metabolic assays) have a strong influence on the results of the experiments and the conclusions drawn from them. A primary example is the question of whether L-Dopa is toxic to doparninergic neurons or whether it provides neurotrophic effects: In pure, neuronal-like cultures, L-Dopa provides toxicity, whereas in the presence of glial cells, it provides trophic effects when applied. The multitude of factors that influence the data generated from cell culture experiments indicates that in order to obtain clear-cut and unambiguous results, investigators need to choose their model carefully and are encouraged to verify their main results with different models
Online_Supplements_(Tables) – Supplemental material for Fertility Intentions and Their Realization in Couples: How the Division of Household Chores Matters
No full textSupplemental material, Online_Supplements_(Tables) for Fertility Intentions and Their Realization in Couples: How the Division of Household Chores Matters by Bernhard Riederer, Isabella Buber-Ennser and Zuzanna Brzozowska in Journal of Family Issues</p
Limitations of cellular models in Parkinson's disease research
No full textCell cultures for Parkinson's disease research have the advantage of virtually unlimited access, they allow rapid screening for disease pathogenesis and drug candidates, and they restrict the necessary number of animal experiments. Limitations of cell cultures, include that the survival of neurons is dependent upon the culture conditions; that the cells do not develop their natural neuronal networks. In most cases, neurons are deprived from the physiological afferent and efferent connections. In Parkinson's disease research, mesencephalic slice cultures, primary immature doparninergic neurons and immortalized cell lines - either in a proliferating state or in a differentiated state - are used. Neuronal cultures may be plated in the presence or absence of glial cells and serum. These different culture conditions as well as the selection of outcome parameters (morphological evaluation, viability assays, biochemical assays, metabolic assays) have a strong influence on the results of the experiments and the conclusions drawn from them. A primary example is the question of whether L-Dopa is toxic to doparninergic neurons or whether it provides neurotrophic effects: In pure, neuronal-like cultures, L-Dopa provides toxicity, whereas in the presence of glial cells, it provides trophic effects when applied. The multitude of factors that influence the data generated from cell culture experiments indicates that in order to obtain clear-cut and unambiguous results, investigators need to choose their model carefully and are encouraged to verify their main results with different models
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
Going Beyond Counting First Authors in Author Co-citation Analysis
No full textThe 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
Appropriate Similarity Measures for Author Cocitation Analysis
No full textWe 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
Dispelling the Myths Behind First-author Citation Counts
No full textWe 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
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