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    Differential expression of SAPK isoforms in the rat brain. An in situ hybridisation study in the adult rat brain and during post-natal development

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    MAPK pathways transduce a broad variety of extracellular signals into cellular responses. Despite their pleiotropic effects and their ubiquitous distribution, surprisingly little is known about their involvement in the communication network of nerve cells. As a first step to elucidate the role of MAPK pathways in neuronal signalling, we studied the distribution of SAPK α/JNK2, SAPK β/JNK3, and SAPK γ/JNK1, three isoforms of SAPK/JNK, a stress-activated MAPK subfamily. We compared the mRNA localisation of the three main isoforms in the adult and developing rat brain using in situ hybridisation. In the adult brain, SAPK α and β were widely but heterogeneously distributed, reproducing the pattern of a probe that does not discriminate the isoforms. Differently, high labelling for the SAPK γ probe was exclusively localised in the endopiriform nucleus and medial habenula. Intermediate staining was detected in the hippocampus. During post-natal development, SAPK β showed the same localisation as in the adult. Nevertheless, the semi-quantitative analysis of optical densities showed significantly different mRNA levels. In the adult, SAPK γ signal was weak, whereas in newborn rats the labelling was intense and widely distributed. SAPK γ mRNA levels decreased during development, to reach the low signals detected in the adult. These results suggest that in the central nervous system SAPK-type MAP kinases perform significant physiological functions which are particularly relevant during post-natal development. The distinct distribution patterns of SAPK isoforms in the adult rat brain support the hypothesis that separate functions are performed by the products of the three SAPK genes

    Localization of the messenger RNA for the c-Jun NH2-terminal kinase kinase in the adult and developing rat brain: An in situ hybridization study

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    Stress-activated protein kinase/extracellular signal-regulated protein kinase-1/c-Jun NH2-terminal kinase kinase is a dual-specificity kinase which phosphorylates and activates stress-activated protein kinase/c-Jun NH2- terminal kinase, a recently discovered mitogen-activated protein kinase that is stimulated by stressful stimuli and that regulates cellular transcriptional activity. The distribution of the messenger RNA encoding for stress-activated protein kinase/extracellular signal-regulated protein kinase-1 was evaluated in the adult and developing rat central nervous system. In situ hybridization with a 35S-labelled 45mer oligodeoxynucleotide probe was used to map the distribution of the stress- activated protein kinase/extracellular signal-regulated protein kinase-1 messenger RNA in postnatal day 1, 3, 6, 9, 12, 15, 18, 21 and adult rat brains. Specific labelling was generally associated with neuronal profiles. In the adult central nervous system, high hybridization signals were observed in the hippocampus, the granular layer of the cerebellum, the medial habenula, the anterodorsal thalamic nucleus, the red nucleus, the pontine nuclei, the facial nucleus, the motor and mesencephalic nuclei of the trigeminal nerve, the hypoglossal nucleus, the vestibular nucleus and the nucleus ambiguus. Intermediate levels were present in diencephalic and mesencephalic regions and in the neocortex, while basal ganglia displayed a low hybridization signal. In the developing brain, the heterogeneous distribution of the hybridization signal observed in the adult brain was already present, but in the hippocampus and basal ganglia the stress- activated protein kinase/extracellular signal-regulated protein kinase-1 messenger RNA levels were significantly higher at postnatal day 3 and during the second postnatal week than in the adult. The results show that stress- activated protein kinase/extracellular signal-regulated protein kinase-1 is widely expressed in the rat central nervous system and co-localizes with its substrate stress-activated protein kinase. The observed changes in stress- activated protein kinase/extracellular signal-regulated protein kinase-1 messenger RNA levels during postnatal development suggest a role for this protein in the maturation of brain circuits

    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

    SARS-CoV-2 and extracellular vesicles: An intricate interplay in pathogenesis, diagnosis and treatment

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    Extracellular vesicles (EVs) are widely recognized as intercellular communication mediators. Among the different biological processes, EVs play a role in viral infections, supporting virus entrance and spread into host cells and immune response evasion. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection became an urgent public health issue with significant morbidity and mortality worldwide, being responsible for the current COVID-19 pandemic. Since EVs are implicated in SARS-CoV-2 infection in a morphological and functional level, they have gained growing interest for a better understanding of SARS-CoV-2 pathogenesis and represent possible diagnostic tools to track the disease progression. Furthermore, thanks to their biocompatibility and efficient immune activation, the use of EVs may also represent a promising strategy for the development of new therapeutic strategies against COVID-19. In this review, we explore the role of EVs in viral infections with a focus on SARS-CoV-2 biology and pathogenesis, considering recent morphometric studies. The common biogenesis aspects and structural similarities between EVs and SARS-CoV-2 will be examined, offering a panoramic of their multifaceted interplay and presenting EVs as a machinery supporting the viral cycle. On the other hand, EVs may be exploited as early diagnostic biomarkers and efficient carriers for drug delivery and vaccination, and ongoing studies will be reviewed to highlight EVs as potential alternative therapeutic strategies against SARS-CoV-2 infection

    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
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