1,720,987 research outputs found
Functional and Molecular Studies of the Crosstalk between Intestinal Microbioma and Enteric Nervous System and Potential Effects on the Gut-Brain Axis
Get PDFL'interazione fra costituenti della parete intestinale e microflora commensale costituisce il principale artefice del mantenimento della barriera mucosale, della promozione dello sviluppo del tratto gastrointestinale (GI) e della modulazione delle funzioni GI. In questo contesto, giocano un ruolo chiave i recettori Toll-like (TLRs), un sistema di proteine che attivano la risposta immunitaria innata e assicurano l'integrità funzionale e strutturale del SNE. In questo studio sono state caratterizzate le alterazioni strutturali e funzionali del SNE murino indotte da: i) cambiamenti nel segnale dell’immunità innata, mediato dal recettore TLR4, ii) una miscela di fosfolipidi ossidati (OxPAPC), implicati nel blocco del segnale generato dai recettori TLR2 e TLR4 e iii) anomalie nella composizione del microbiota.
Data l’importanza di un corretto segnale TLRs-dipendente nel mantenimento della rete nervosa e del codice neurochimico del SNE, segmenti di ileo provenienti da topi WT e TLR4-/- hanno evidenziato anomalie nell’attività contrattile neuromuscolare associate ad un’eccessiva modulazione inibitoria da NO ed ATP, a sostegno della presenza di un dialogo tra TLR4, SNE e microflora, fondamentale per la modulazione della funzione neuromuscolare. Studi strutturali su preparati di ileo di topi TLR4-/- evidenziano un’alterata architettura del SNE a livello gliale, indicando un coinvolgimento del recettore TLR4 nel mantenimento dell'integrità della rete gliale enterica mediato dalla produzione di ATP e della trasmissione purinergica evidenziano il ruolo di TLR4 nell’omeostasi strutturale e funzionale del SNE. Inoltre, è stato dimostrato che la mancanza del recettore TLR4 determina nell’ippocampo, come a livello del SNE, una compromessa neuroplasticità caratterizzata da alterazioni nella densità neuronale associata a variazioni della distribuzione della rete gliale, a confermare un ruolo fondamentale del segnale TLRs anche a livello centrale.
In parallelo, è stato indagato il ruolo del segnale mediato dai TLRs nell’asse microbiota-TLRs-SNE, tramite la somministrazione in acuto con OxPAPC, inibitore del segnale mediato da entrambi i recettori TLR2 e TLR4, in topi adolescenti (3 ± 1 settimane). Il trattamento con OxPAPC ha causato un’alterazione significativa della risposta neuromuscolare associata a modifiche della rete neuro-gliale del SNE, confermando l’importanza del segnale mediato da tali recettori nell'assicurare l’integrità funzionale e strutturale del SNE durante l'adolescenza. Recenti studi riportano un ruolo primario nel dialogo tra i recettori TLRs e il sistema serotoninergico ed è stato evidenziato come OxPAPC comporti iperesponsività alla serotonina, alterazioni nella distribuzione recettoriale serotoninergica associata a variazioni nel metabolismo del triptofano, a sostegno della presenza di un dialogo tra immunità innata e sistema serotoninergico.
Al fine di approfondire il ruolo dell'asse microbiota-intestino nell’omeostasi del SNE è stato messo a punto un modello animale di deplezione di microbiota intestinale attraverso la somministrazione di 4 antibiotici a topi adolescenti. Tale trattamento ha determinato un fenotipo simil germ-free ed alterazioni della motilità intestinale e dell'integrità della rete neuronale e gliale enterica. Data l’importanza di una corretta composizione del microbiota commensale nel mantenimento del codice neurochimico del SNE che nella produzione di neurotrasmettitori a livello enterico, sono state studiate le vie di neurotrasmissione coinvolte nella sensibilità viscerale. Un’alterata composizione del microbiota intestinale altera la sensibilità viscerale associata anomalie nella risposta neuromuscolare alla serotonina accompagnate da una compromessa rete recettoriale serotoninergica e del metabolismo del triptofano, sottolineando l’importanza di una corretta composizione del microbiota nel mantenimento delle funzioni mediate dal sistema serotoninergico
Lipid-based DNA/siRNA transfection agents disrupt neuronal bioenergetics and mitophagy
No full textA multitude of natural and artificial compounds have been recognized to modulate autophagy, providing direct or, through associated pathways, indirect entry points to activation and inhibition. While these pharmacological tools are extremely useful in the study of autophagy, their abundance also suggests the potential presence of unidentified autophagic modulators that may interfere with experimental designs if applied unknowingly. Here, we report unanticipated effects on autophagy and bioenergetics in neuronal progenitor cells (NPCs) incubated with the widely used lipid-based transfection reagent lipofectamine (LF), which induced mitochondria depolarization followed by disruption of electron transport. When NPCs were exposed to LF for 5 h followed by 24, 48, and 72 h in LF-free media, an immediate increase in mitochondrial ROS production and nitrotyrosine formation was observed. These events were accompanied by disrupted mitophagy (accumulation of dysfunctional and damaged mitochondria, and of LC3II and p62), in an mTOR- and AMPK-independent manner, and despite the increased mitochondrial PINK1 (PTEN-inducible kinase 1) localization. Evidence supported a role for a p53-mediated abrogation of parkin translocation and/or abrogation of membrane fusion between autophagosome and lysosomes. While most of the outcomes were LF-specific, only two were shared by OptiMEM exposure (with no serum and reduced glucose levels) albeit at lower extents. Taken together, our findings show that the use of transfection reagents requires critical evaluation with respect to consequences for overall cellular health, particularly in experiments designed to address autophagy-inducing effects and/or energy stress.</jats:p
Effects of Toll-like receptors 2 and 4 inhibition in intestinal contractility and in serotonergic system of mouse enteric nervous system
No full textClinical features and psychological impact of celiac disease at diagnosis
No full textWe aimed to describe the socio-demographic, behavioral and clinical profiles of adult patients with newly diagnosed celiac disease (CeD) and their possible association with QoL and psychological symptoms
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Get PDF“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
Get PDFWe 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
Get PDFWe 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
- …
