1,720,957 research outputs found
Parkinson’s disease and mitochondrial disfunctions: exploring the effect of PARK2 mutations in human skin fibroblasts
Full text linkParkinson’s disease is a complex and multifactorial neurodegenerative disease whose etiology has not been totally clarified yet. Strong evidences suggest that a complex interplay between environmental and genetic factors are involved in PD pathogenesis. Many of the molecular pathways implicated in PD etiology converge on mitochondria, resulting in their dysfunction. Mutations in PARK2 gene are the most frequent cause of familial forms of PD. This gene encodes Parkin, an E3 ubiquitin ligase involved in the mitophagy process. Parkin loss-of-function is responsible for the cellular accumulation of damaged mitochondria. Given the importance of mitochondrial dysfunctions and mitophagy impairment in PD pathogenesis, PARK2-mutated primary skin fibroblasts were used as a cellular model to explore the effects of PARK2 mutations both on the mitochondrial function and morphology and on the total and mitochondrial proteome. The first part of this thesis investigates the impact of Parkin impairment on mitochondrial function and network in primary skin fibroblasts of five PARK2 patients and five control subjects. The second part of this project is focused on the characterization of the mitochondrial and the total proteome alterations that characterize patients carrying PARK2 mutations. In conclusion, the present work highlighted new molecular factors and pathways altered by PARK2 mutations, which will unravel possible biochemical pathways altered in the sporadic form of the disease. The Peptide Transporters of teleost fish, an emerging model in translational research: functional characterization and comparative study of SLC15A1a (PepT1a) and SLC15A1b (PepT1b) transporters
Network analysis identifies disease-specific pathways for parkinson’s disease
Full text linkNeurodegenerative diseases are characterized by the progressive loss of specific neurons in selected regions of the central nervous system. The main clinical manifestation (movement disorders, cognitive impairment, and/or psychiatric disturbances) depends on the neuron population being primarily affected. Parkinson’s disease is a common movement disorder, whose etiology remains mostly unknown. Progressive loss of dopaminergic neurons in the substantia nigra causes an impairment of the motor control. Some of the pathogenetic mechanisms causing the progressive deterioration of these neurons are not specific for Parkinson’s disease but are shared by other neurodegenerative diseases, like Alzheimer’s disease and amyotrophic lateral sclerosis. Here, we performed a meta-analysis of the literature of all the quantitative proteomic investigations of neuronal alterations in different models of Parkinson’s disease, Alzheimer’s disease, and amyotrophic lateral sclerosis to distinguish between general and Parkinson’s disease-specific pattern of neurodegeneration. Then, we merged proteomics data with genetics information from the DisGeNET database. The comparison of gene and protein information allowed us to identify 25 proteins involved uniquely in Parkinson’s disease and we verified the alteration of one of them, i.e., transaldolase 1 (TALDO1), in the substantia nigra of 5 patients. By using open-source bioinformatics tools, we identified the biological processes specifically affected in Parkinson’s disease, i.e., proteolysis, mitochondrion organization, and mitophagy. Eventually, we highlighted four cellular component complexes mostly involved in the pathogenesis: the proteasome complex, the protein phosphatase 2A, the chaperonins CCT complex, and the complex III of the respiratory chain
Systems biology analysis of the proteomic alterations in Parkinson's disease: Common and disease-specific pathways
No full textObjectives: Many biochemical mechanisms have been proposed to play a role in different neurodegenerative disorders. To distinguish what is disease-specific from what is generically linked to a neurodegenerative state is essential to better describe Parkinson's disease (PD) pathogenesis. PD and Amyotrophic Lateral Sclerosis (ALS) share some common mechanisms. Moreover, a high incidence of comorbidity may be explained by common biochemical altered pathways.
Methods: We performed a bioinformatics meta-analysis of all the proteomic investigations of neuronal alterations in PD, ALS and Alzheimer's disease (AD), used as control (non-motor neurodegenerative disease). We combined these data with genes found in a curated disease-gene database (DisGeNET). Moreover, we are currently going to analyze Peripheral Blood Mononuclear Cells samples coming from 20 ALS patients, 20 PD patients and 20 comorbid ALS/PD patients by two-dimensional electrophoresis.
Results: From our bioinformatics analysis some proteins were associated uniquely to PD, whereas others were associated to both diseases. Biological processes mostly associated to PD turned out to be chromatin organization, mitochondrion organization and protein folding. In addition, we found common dysregulated pathways, i.e., translation, SRP-dependent protein targeting to membrane and protein transport.
Conclusions: PD and ALS pathogenesis have some common mechanisms, due to the fact that they are both neurodegenerative diseases. The combination of bioinformatics tools and proteomic analysis of samples coming from comorbid patients will allow u also to highlight the disease-specific pathways, which may justify the degeneration of different neuron populations
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
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
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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