1,721,000 research outputs found
Proteome effects of antidepressant medications.
No full textIn this review, we give an overview of the proteomic investigations aimed at elucidating the impact of antidepressants treatment on brain at the molecular level. We discuss the animal models in which currently available treatments of mood disorders have been investigated by proteomic approaches, with a critical analysis of the main studies and a comparison of the methodologies used. The results are reviewed in the light of the putative mechanism of action of antidepressant therapies, and overall suggest an activation of long-term events downstream of the neurotransmitter signalling
Progresses and challenges in Strongyloides spp. proteomics
No full textThe availability of high-quality data of helminth genomes provided over the past two decades has supported and accelerated large-scale 'omics studies and, consequently, the achievement of a more in-depth molecular characterization of a number of pathogens. This has also involved Strongyloides spp. and since their genome was made available transcriptomics has been rather frequently applied to investigate gene expression regulation across their life cycle. Strongyloides proteomics characterization has instead been somehow neglected, with only a few reports performing high-throughput or targeted analyses associated with protein identification by tandem mass spectrometry. Such investigations are however necessary in order to discern important aspects associated with human strongyloidiasis, including understanding parasite biology and the mechanisms of host-parasite interaction, but also to identify novel diagnostic and therapeutic targets. In this review article, we will give an overview of the published proteomics studies investigating strongyloidiasis at different levels, spanning from the characterization of the somatic proteome and excretory/secretory products of different parasite stages to the investigation of potentially immunogenic proteins. Moreover, in the effort to try to start filling the current gap in host-proteomics, we will also present the first serum proteomics analysis in patients suffering from human strongyloidiasis. This article is part of the Theo Murphy meeting issue 'Strongyloides: omics to worm-free populations'
Escitalopram modulates neuron-remodelling proteins in a rat gene-environment interaction model of depression as revealed by proteomics. Part I: genetic background.
No full textThe wide-scale analysis of protein expression provides a powerful strategy for the molecular exploration of complex pathophysiological mechanisms, such as the response to antidepressants. Using a 2D proteomic approach we investigated the Flinders Sensitive Line (FSL), a genetically selected rat model of depression, and the control Flinders Resistant Line (FRL). To evaluate gene–environment interactions, FSL and FRL pups were separated from their mothers for 3 h (maternal separation, MS), as early-life trauma is considered an important antecedent of depression. All groups were treated with either escitalopram (Esc) admixed to food (25 mg/kg.d) or vehicle for 1 month. At the week 3, forced swim tests were performed. Protein extracts from prefrontal/frontal cortex and hippocampus were separated by 2D electrophoresis. Proteins displaying statistically significant differences in expression levels were identified by mass spectrometry. Immobility time values in the forced swim test were higher in FSL rats and reduced by antidepressant treatment. Moreover, the Esc-induced reduction in immobility time was not detected in MS rats. The impact of genetic background in response to Esc was specifically investigated here. Bioinformatics analyses highlighted gene ontology terms showing tighter associations with the modulated proteins. Esc modulated protein belonging to cytoskeleton organization in FSL; carbohydrate metabolism and intracellular transport in FRL. Proteins differently modulated in the two strains after MS and Esc play a role in cytoskeleton organization, vesicle-mediated transport, apoptosis regulation and macromolecule catabolism. These findings suggest pathways involved in neuronal remodelling as molecular correlates of response to antidepressants in a model of vulnerability
Escitalopram affects cytoskeleton and synaptic plasticity pathways in a rat gene-environment interaction model of depression as revealed by proteomics. Part II: environmental challenge.
No full textLarge-scale investigations aimed at elucidating the molecular mechanism of action of antidepressant treatment are achievable through the application of proteomic technologies. We performed a proteomic study on the Flinders Sensitive Line (FSL), a genetically selected rat model of depression, and the control Flinders Resistant Line (FRL). To evaluate gene–environment interactions, FSL and FRL animals were separated from their mothers for 3 h from postnatal days 2 to 14 (maternal separation ; MS), since early-life trauma is considered an important antecedent of depression. All groups received either escitalopram (Esc) admixed to food pellets (25 mg/kg.d) or vehicle for 1 month. Protein extracts from prefrontal/frontal cortex and hippocampus were separated by 2D electrophoresis. Proteins differentially modulated were identified by mass spectrometry. Bioinformatics analyses were performed to discover gene ontology terms associated with the modulated proteins. This paper was focused on the modifications induced by the environmental challenge of MS, both on the predisposed genetic background and on the resistant phenotype. The combination between Esc treatment and MS was investigated by comparing the MS, Esc-treated rats with rats subjected to each single procedure. In MS rats, antidepressant treatment influenced mainly proteins involved in carbohydrate metabolism in FSL rats and in vesicle-mediated transport in FRL rats. When studying the interaction between Esc and MS vs. non-separated rats, proteins playing a role in cytoskeleton organization, neuronal development, vesicle-mediated transport and synaptic plasticity were identified. The results provide further support to the available reports that antidepressant treatment affects intracellular pathways and also suggest new potential targets for future therapeutic intervention
Proteomic analysis of rat brain tissue: Comparison of protocols for two-dimensional gel electrophoresis analysis based on different solubilizing agents
No full textThe present study reports a comparison of recently described solubilizing methods, to set up a simple protocol for obtaining two-dimensional (2-D) gel electrophoresis maps of brain tissue. Different protocols were used for preparing rat brain homogenates and the resulting maps were compared by image analysis. Three different detergents, two delipidation methods, and introduction of a fractionation step based on different protein solubility in surfactants, were evaluated. When using efficient zwitterionic detergents (3-[(3-cholamidopropyl)dimethylamino]-1-propanesulfonate, CHAPS; amidosulfobetaine 14, ASB-14), the patterns obtained by direct loading of total extracts were qualitatively overlapping with patterns obtained from fractionated samples. In contrast, a weaker nonionic agent (Nonidet P-40, NP-40) produced a different protein pattern in the collected fractions. Delipidation did not improve the results for all the different extraction methods. Immunoblots performed with antibodies recognizing cytosolic and membrane-spanning proteins, which were detected as nondegraded spots, showed that membrane proteins with intermediate molecular mass could be recovered. We suggest, as a simple and efficient method for preparing rat brain, maps, the homogenization in a solution containing an efficient zwitterionic surfactant, which allows to solubilize cytosolic and membrane proteins in a single step. Alternatively, a fractionation can be carried out on samples homogenized by a weak solubilizing agent, a more labor-intensive effort resulting in a larger number of proteins on two maps
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
Proteomics of rat hypothalamus, hippocampus and pre-frontal/frontal cortex after central administration of the neuropeptide PACAP
No full textPituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide that exerts pleiotropic functions, acting as a hypophysiotropic factor, a neurotrophic and a neuroprotective agent. The molecular pathways activated by PACAP to exert its physiological roles in brain are incompletely understood. In this study, adrenocorticotropic hormone (ACTH), prolactin, luteinising hormone (LH), follicle-stimulating hormone (FSH), thyroid-stimulating hormone (TSH), brain-derived neurotrophic factor and corticosterone blood levels were determined before and 20, 40, 60, and 120 min after PACAP intracerebroventricular administration. PACAP treatment increased ACTH, corticosterone, LH and FSH blood concentrations, while it decreased TSH levels. A proteomics investigation was carried out in hypothalamus, hippocampus and pre-frontal/frontal cortex (P/FC) using 2-dimensional gel electrophoresis at 120 min, the end-point suggested by studies on PACAP hypophysiotropic activities. Spots showing statistically significant alterations after PACAP treatment were identified by Matrix-assisted laser desorption/ionization-Time of flight mass spectrometry. Identified proteins were consistent with PACAP involvement in different molecular processes in brain. Altered expression levels were observed for proteins involved in cytoskeleton modulation and synaptic plasticity: actin in the hypothalamus; stathmin, dynamin, profilin and cofilin in hippocampus; synapsin in P/FC. Proteins involved in cellular differentiation were also modulated: glutathione-S-transferase α and peroxiredoxin in hippocampus; nucleoside diphosphate kinase in P/FC. Alterations were detected in proteins involved in neuroprotection, neurodegeneration and apoptosis: ubiquitin carboxyl-terminal hydrolase isozyme L1 and heat shock protein 90-β in hypothalamus; α-synuclein in hippocampus; glyceraldehyde-3-phosphate dehydrogenase and prohibitin in P/FC. This proteomics study identified new proteins involved in molecular mechanisms mediating PACAP functions in the central nervous system
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