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Action of ciliary neurotrophic factor on mouse brain feeding centers
Full text linkIl fattore neurotrofico ciliare (CNTF) induce sazietà e aumento della spesa energetica nell’uomo e nei roditori, agendo a livello cellulare con un meccanismo simile a quello della leptina, attraverso la via di trasduzione Jak-STAT3. Studi recenti hanno evidenziato che nell’ipotalamo tuberale di topo il CNTF è espresso da cellule gliali e il suo meccanismo d’azione è potenziato in modelli sperimentali di obesità. Mediante studi di immunoistochimica, abbiamo dimostrato che la somministrazione di CNTF induce l’attivazione di STAT1 e STAT5 nell’ipotalamo tuberale, in particolare nelle cellule ependimali del terzo ventricolo, nei β-taniciti e cellule gliali dell’eminenza mediana. In questa sede, inoltre, il CNTF attiva il c-Fos, marker di attivazione cellulare. Abbiamo poi verificato l’ipotesi che il CNTF potesse agire anche a livello dei centri truncali, altra sede importante per il controllo del comportamento alimentare. Il CNTF nell’area postrema di topo, come nell’eminenza mediana, attiva STAT3, STAT1 e STAT5. Studi di co-localizzazione hanno evidenziato che gran parte di queste cellule gliali responsive al CNTF esprimono tipici marker di immaturità, nestina e vimentina. Dopo 120 minuti dal trattamento con CNTF abbiamo osservato una forte attivazione di c-Fos nei neuroni del nucleo del tratto solitario e una debole attivazione dello stesso marker in alcuni neuroni colinergici del nucleo motore dorsale del vago. Il doppio trattamento con CNTF (120 minuti, per indurre espressione di c-Fos) e con leptina (25 minuti, per indurre fosforilazione di STAT3) ha permesso di dimostrare la co-localizzazione dei due marker in una piccola popolazione di neuroni nella porzione caudale del nucleo del tratto solitario. Inoltre, nell’area postrema, si evidenzia una notevole discrepanza tra le numerose cellule responsive al CNTF e quelle che lo producono, le quali sono poche cellule gliali situate nel funiculus separans e nelle meningi. Questo disaccoppiamento tra espressione del CNTF e del suo recettore è stato confermato da studi di RT-qPCR, sia a livello dell’area postrema che dell’ipotalamo. Il CNTF rappresenta quindi un nuovo fattore di sazietà coinvolto nella regolazione del bilancio energetico che esercita un’azione parallela e ridondante a livello dell’ipotalamo e del tronco encefalico.The ciliary neurotrophic factor (CNTF) induces satiety and increase of energy expenditure in rodents and human through a leptin-like activation of the Jak-STAT3 signaling pathway. Recent studies demonstrated that CNTF is constitutively produced by hypothalamic glial cells and that its expression is up-regulated in obese mice. By immunohistochemistry studies, we demonstrated that after systemic treatment, rat recombinant CNTF induced activation of STAT1 and STAT5 in the tuberal hypothalamus of mice, in particular in ependymal cells bordering the third ventricle floor and lateral recesses, and in median eminence β-tanycytes and glial cells. Moreover, STAT activation was accompanied by c-Fos expression in β-tanycytes and median eminence cells of CNTF-treated mice. We tested the hypothesis that CNTF also affects the brainstem centers involved in energy homeostasis. In the area postrema of mice, as well as in the median eminence, CNTF activates STAT3, STAT1 and STAT5. Co-localization studies showed that a significant proportion of CNTF-responsive glial cells were also positive for immaturity and plasticity markers nestin and vimentin. After 120 min from the treatment, we observed a strong c-Fos expression in several neurons of the rostral and caudal solitary tract nucleus (NTS) and a weak c-Fos immunostaining in some cholinergic neurons of the dorsal motor nucleus of the vagus. Treatment with CNTF (120 min, to induce c-Fos expression) and leptin (25 min, to induce STAT3 phosphorylation) demonstrated the co-localization of the two markers in a small percentage of neurons in the caudal NTS portion. In contrast to the high responsiveness to CNTF, in the area postrema CNTF immunoreactivity is weak and sparse, and mainly detected in glial cells of the funiculus separans and meninges. RT-qPCR in micropunched area postrema and hypothalamus mouse tissues highlights the big discrepancy between CNTF and CNTF receptor expression in both the two brain regions examined.
In conclusion, CNTF represents a new satiety factor involved in the pathophysiological regulation of the energy balance that exerts a parallel and redundant action in hypothalamic and brainstem feeding centers
Neuronal nitric oxyde synthase positive neurons in human indusium griseum
Full text linkThe study was designed to analyze the nNOS positive neurons present in the indusium griseum by describing their distribution and morphology. To this purpose, sagittal serial sections from paraffin or frozen autopsy specimens of corpus callosum including the overlying indusium griseum were processed by immunohistochemistry and immunofluorescence, using an antibody against the neuronal form of the enzyme nitric oxyde synthase. To test the specificity of the antibody used, Western Blot was performed in the indusium griseum of the same specimens. The stainings revealed the presence of many neuronal nitric oxyde synthase-immunopositive neurons in human indusium griseum, located along both rostral-caudal and medio-lateral directions. In particular, they were more numerous 1 mm apart from the midline, and their number peaked over the body of the corpus callosum. They showed different morphologies; in some cases, they were located at the boundary between indusium griseum and corpus callosum, more densely packed in proximity to the pial arteries penetrating into the corpus callosum. The significant presence and distribution of neuronal nitric oxyde synthase-immunopositive neurons suggests that indusium griseum likely plays a functional role in the neurovascular regulation within the corpus callosum. Schematic representation of human adult IG and the neurovascular unit originating from sopracallosal artery (Sca) that branches into smaller arterioles (Br) (created in PowerPoint). The arterioles cross the three layers of IG (layers I, II and III) and penetrate into the CC separated from IG by the Virchow-Robin space (VRs). As the arterioles go deeper, this space disappears and the vascular basement membrane comes into direct contact with the astrocytic end-feets (intracallosal arterioles and capillaries). nNOS-immunopositive neurons (nNOSIP N) surround the arterioles and control the vasomotore tone secreting nitric oxyde (NO). Two morphological types of nNOSIP N can be appreciated by the use of different colors: fusiform (blue) and ovoidal (pink). Also NeuN-immunopositive neurons (N) and many astrocytes (As) are present, more numerous in IG than in CC
Ciliary neurotrophic factor (CNTF) and its receptor (CNTFRα) signal through MAPK/ERK pathway in human prostate tissues: a morphological and biomolecular study
No full textCiliary neurotrophic factor (CNTF) is a member of interleukin-6 type cytokine family. The CNTF receptor complex is a heterodimer including gp130 and CNTF receptor α (CNTFRα) proteins triggering the activation of multiple intracellular signaling pathways including AKT/PI3K, MAPK/ERK and Jak/STAT pathways. At present no data are available on the localization of CNTF and CNTFRα in prostate as well as on the role of CNTF in this organ. In this study we have analyzed the localization of CNTF and CNTFRα by immunohistochemistry and we have used PWR-1E cell line as a model for normal glandular cell to investigate the role of this cytokine. Our results show that CNTF and CNTFRa are expressed in the staminal compart of the prostate and that CNTF selectively inhibits ERK pathway. In conclusion, we suggest that CNTF could be considered as key molecule to maintenance epithelium homeostasis via pERK downregulation by an autocrine mechanism. Further CNTF studies in prostate cancer could be useful to verify the potential role of this cytokine in carcinogenesis
Activation of transcription factors STAT1 and STAT5 in the mouse median eminence after systemic ciliary neurotrophic factor administration
No full textExogenously administered ciliary neurotrophic factor (CNTF) causes weight loss in obese rodents and humans through leptin-like activation of the Jak-STAT3 signaling pathway in hypothalamic arcuate neurons. Here we report for the first time that 40min after acute systemic treatment, rat recombinant CNTF (intraperitoneal injection of 0.3mg/kg of body weight) induced nuclear translocation of the tyrosine-phosphorylated forms of STAT1 and STAT5 in the mouse median eminence and other circumventricular organs, including the vascular organ of the lamina terminalis and the subfornical organ. In the tuberal hypothalamus of treated mice, specific nuclear immunostaining for phospo-STAT1 and phospho-STAT5 was detected in ependymal cells bordering the third ventricle floor and lateral recesses, and in median eminence cells. Co-localization studies documented STAT1 and STAT5 activation in median eminence β-tanycytes and underlying radial glia-like cells. A few astrocytes in the arcuate nucleus responded to CNTF by STAT5 activation. The vast majority of median eminence tanycytes and radial glia-like cells showing phospho-STAT1 and phospho-STAT5 immunoreactivity were also positive for phospho-STAT3. In contrast, STAT3 was the sole STAT isoform activated by CNTF in arcuate nucleus and median eminence neurons. Finally, immunohistochemical evaluation of STAT activation 20, 40, 80, and 120min from the injection demonstrated that cell activation was accompanied by c-Fos expression. Collectively, our findings show that CNTF activates STAT3, STAT1, and STAT5 in vivo. The distinctive activation pattern of these STAT isoforms in the median eminence may disclose novel targets and pathways through which CNTF regulates food intake
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
HTRA1 in Placental Cell Models: A Possible Role in Preeclampsia
Full text linkThe HtrA serine peptidase 1 (HTRA1) is a multidomain secretory protein with serine–protease activity involved in the regulation of many cellular processes in both physiological and pathological conditions. HTRA1 is normally expressed in the human placenta, and its expression is higher in the first trimester compared to the third trimester, suggesting an important role of this serine protease in the early phases of human placenta development. The aim of this study was to evaluate the functional role of HTRA1 in in vitro models of human placenta in order to define the role of this serine protease in preeclampsia (PE). BeWo and HTR8/SVneo cells expressing HTRA1 were used as syncytiotrophoblast and cytotrophoblast models, respectively. Oxidative stress was induced by treating BeWo and HTR8/SVneo cells with H2O2 to mimic PE conditions in order to evaluate its effect on HTRA1 expression. In addition, HTRA1 overexpression and silencing experiments were performed to evaluate the effects on syncytialization, cell mobility, and invasion processes. Our main data showed that oxidative stress significantly increased HTRA1 expression in both BeWo and HTR8/SVneo cells. In addition, we demonstrated that HTRA1 has a pivotal role in cell motility and invasion processes. In particular, HTRA1 overexpression increased while HTRA1 silencing decreased cell motility and invasion in HTR8/SVneo cell model. In conclusion, our results suggest an important role of HTRA1 in regulating extravillous cytotrophoblast invasion and motility during the early stage of placentation in the first trimester of gestation, suggesting a key role of this serine protease in PE onset
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