1,721,020 research outputs found

    Experimental early‐life febrile seizures cause a sustained increase in excitatory neurotransmission in newborn dentate granule cells

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    Prolonged febrile seizures (FS) are a risk factor for the development of hippocampal-associated temporal lobe epilepsy. The dentate gyrus is the major gateway to the hippocampal network and one of the sites in the brain where neurogenesis continues postnatally. Previously, we found that experimental FS increase the survival rate and structural integration of newborn dentate granule cells (DGCs). In addition, mature post-FS born DGCs express an altered receptor panel. Here, we aimed to study if these molecular and structural changes are accompanied by an altered cellular functioning. Experimental FS were induced by hyperthermia in 10-days-old Sprague-Dawley rats. Proliferating progenitor cells were labeled the next day by injecting green fluorescent protein expressing retroviral particles bilaterally in the dentate gyri. Eight weeks later, spontaneous excitatory and inhibitory postsynaptic events (sEPSCs and sIPSCs, respectively) were recorded from labeled DGCs using the whole-cell patch-clamp technique. Experimental FS resulted in a robust decrease of the inter event interval (p < .0001) and a small decrease of the amplitude of sEPSCs (p < .001). Collectively the spontaneous excitatory charge transfer increased (p < .01). Experimental FS also slightly increased the frequency of sIPSCs (p < .05), while the amplitude of these events decreased strongly (p < .0001). The net inhibitory charge transfer remained unchanged. Experimental, early-life FS have a long-term effect on post-FS born DGCs, as they display an increased spontaneous excitatory input when matured. It remains to be established if this presents a mechanism for FS-induced epileptogenesis.Funding information: ‘Bijzonder Onderzoeksfonds’ grant from Hasselt Universit

    Proteomics en peptidomics in de zoektocht naar (vroege) biomerkers voor astma

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    Occupational asthma (OA) is the most common work-related lung disease in the industrialized world and is characterized by reversible airway obstruction, non-specific airway hyperreactivity and airway inflammation. In 90% of the cases, a complaints-free latency period precedes the development of immunologically mediated OA resulting in late diagnosis of these workers. Proteomics and peptidomics techniques could help to find (new) proteins or peptides related to the pathophysiology and onset of OA, leading to novel biomarkers to identify ‘sensitized’ workers. So far, theuse of these techniques in pulmonary research is limited. The research unit of Lung Toxicology has described a well-characterized and validated mouse model of chemical-induced asthma. Two dermal sensitizations and a single airway challenge with a chemical sensitizer, such as toluene diisocyanate resulted in several phenotypical characteristics of chemical-induced asthma, including lymphocyte proliferation and activation, non-specific airway hyperreactivity and neutrophilic lung inflammation. In this doctoral thesis we focused on:a) applying a proteomics approach to find biomarkers of sensitization caused by chemicals and biomarkers of chemical-induced asthma (Chapter 2 and 3)b) investigating the role of B lymphocytes during sensitization (Chapter 4)c) optimizing a label-free peptidomics approach to study peptide biomarkers (Chapter 5) We used two dimensional difference gel electrophoresis (2D-DIGE) to search for possible biomarkers of sensitization in auricular lymph nodes and serum of mice that were sensitized once andtwice. In the auricular lymph nodes, a large portion of the differentially expressed proteins are structural proteins (e.g. actin, vimentin), while another substantial group are immune related proteins (e.g. lymphocyte specific protein-1, coronin 1a). Most of the identified proteins in serum, after one or two sensitizations are involved in binding/transport (e.g. hemopexin, apolipoprotein E). Three potential biomarkers, lymphocyte specific protein-1, coronin 1a and hemopexin, were verified in an independent experiment by Western blot analysis or ELISA. In a next step, we aim to validate this set of proteins in TDI-exposed workerswith the potential of advancing early diagnosis of OA. To investigate possible biomarkers of disease (chemical-induced asthma), we compared the proteome changes in auricular lymph nodes, bronchoalveolar lavage (BAL) and serum of mice after the establishment of asthma. A majority of differentially expressed proteins (e.g. lymphocyte specific protein-1, vitamin D binding protein, apolipoprotein E, hemopexin and haptoglobin) could be directly linked to inflammation (both locally in the lung as systemically in serum), a hallmark of asthma. For the first time,a systematic proteomics approach was implemented using different samples obtained from the same mice in the setting of chemical-induced asthma.The role of B lymphocytes in the development of chemical-induced asthma is still unclear. Recently, it was shown that B lymphocytes from sensitized mice could carry a ‘sensitized signature’ compared to B lymphocytes of naïve mice. We isolated B lymphocytes from sensitized and non-sensitized mice and studied this ‘sensitized signature’ by using 2D-DIGE. The altered expression of cyclophilin A, cofilin 1 and zinc finger containing CCHC domain protein 11 in sensitized B lymphocytes could be linked directly to the function of B lymphocytes as initiators of T lymphocyte independent asthma-like responses. The low molecular weight proteome ( In conclusion, the introduction of proteomics and (in a lesser extent) peptidomics in a mouse model of chemical-induced asthma has led to the discovery of several potential biomarkers of sensitization and disease, encouraging further validation of these results in humans.status: Publishe

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The 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

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    “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

    Experimental febrile seizures increase dendritic complexity of newborn dentate granule cells

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    Objective: Febrile seizures (FS) are fever-associated convulsions, being the most common seizure disorder in early childhood. A subgroup of these children later develops epilepsy characterized by a hyperexcitable neuronal network in the hippocampus. Hippocampal excitability is regulated by the hippocampal dentate gyrus (DG) where postnatal neurogenesis occurs. Experimental FS increase the survival of newborn hippocampal dentate granule cells (DGCs), yet the significance of this neuronal subpopulation to the hippocampal network remains unclear. In the current study, we characterized the temporal maturation and structural integration of these post-FS born DGCs in the DG. Methods: Experimental FS were induced in 10-day-old rat pups. The next day, retroviral particles coding for enhanced green fluorescent protein (eGFP) were stereotactically injected in the DG to label newborn cells. Histochemical analyses of eGFP expressing DGCs were performed one, 4, and 8 weeks later and consisted of the following: (1) colocalization with neurodevelopmental markers doublecortin, calretinin, and the mature neuronal marker NeuN; (2) quantification of dendritic complexity; and (3) quantification of spine density and morphology. Results: At neither time point were neurodevelopmental markers differently expressed between FS animals and normothermia (NT) controls. One week after treatment, DGCs from FS animals showed dendrites that were 66% longer than those from NT controls. At 4 and 8 weeks, Sholl analysis of the outer 83% of the molecular layer showed 20-25% more intersections in FS animals than in NT controls (p <0.01). Although overall spine density was not affected, an increase in mushroom-type spines was observed after 8 weeks. Significance: Experimental FS increase dendritic complexity and the number of mushroom- type spines in post-FS born DGCs, demonstrating a more mature phenotype and suggesting increased incoming excitatory information. The consequences of this hyperconnectivity to signal processing in the DG and the output of the hippocampus remain to be studied

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We 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

    Coupling matters - A combination of liquid chromatography and mass spectrometry for peptidomic research

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    The guest authors describe the use of LC-MS for the analysis of peptides. They deal with peptide extraction, peptidomic analysis in organisms with and without genomic databases, identification of peptides with conserved N- and C- terminal sequences, and in situ MALDI-TOF peptide profiling.status: Publishe
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