Melanocortins and the cholinergic anti-inflammatory pathway.

Experimental evidence indicates that small concentrations of inflammatory molecules produced by damaged tissues activate afferent signals through ascending vagus nerve fibers, that act as the sensory arm of an "inflammatory reflex". The subsequent activation of vagal efferent fibers, which represent the motor arm of the inflammatory reflex, rapidly leads to acetylcholine release in organs of the reticuloendothelial system. Acetylcholine interacts with α7 subunit-containing nicotinic receptors in tissue macrophages and other immune cells and rapidly inhibits the synthesis/release of tumor necrosis factor-α and other inflammatory cytokines. This neural anti-inflammatory response called "cholinergic anti-inflammatory pathway" is fast and integrated through the central nervous system. Preclinical studies are in progress, with the aim to develop therapeutic agents able to activate the cholinergic anti-inflammatory pathway. Melanocortin peptides bearing the adrenocorticotropin/α-melanocyte-stimulating hormone sequences exert a protective and life-saving effect in animals and humans in conditions of circulatory shock. These neuropeptides are likewise protective in other severe hypoxic conditions, such as prolonged respiratory arrest, myocardial ischemia, renal ischemia and ischemic stroke, as well as in experimental heart transplantation. Moreover, experimental evidence indicates that melanocortins reverse circulatory shock, prevent myocardial ischemia/reperfusion damage and exert neuroprotection against ischemic stroke through activation of the cholinergic anti-inflammatory pathway. This action occurs via stimulation of brain melanocortin MC3/MC4 receptors. Investigations that determine the molecular mechanisms of the cholinergic anti-inflammatory pathway activation could help design of superselective activators of this pathway

Adeno-associated viral vector-mediated human vascular endothelial growth factor gene transfer stimulates angiogenesis and wound healing in the genetically diabetic mouse

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Lie for me: How empathy, alexithymia and emotional intelligence influence the ability to conform facial expression to a prosocial untrue verbal message

The aim of this work was to investigate the association between emotional variables (empathy, emotional intelligence, alexithymia) and lying skills. The hypothesis was that a higher emotional competence was associated to a better ability to lie. In an experimental setting, thirty-four participants were videotaped in two separate session: The first in which they were telling the truth and the second in which, motivated by a social and empathetical intention, they were lying about some emotionally arousing images they viewed. Moreover, all participant filled three self-report questionnaires: The 20-Item Toronto Alexithymia Scale, The Interpersonal Reactivity Index and The Trait Emotional Intelligence Questionnaire Short Form. The coding of facial responses was carried out using the Facial Action Coding System. The findings suggested that emotional competence is associated with the ability to lie and to conform facial expression to a prosocial untrue statement. Conversely, individuals with higher levels of alexithymia and lower emotional ability manifested more marker of discomfort as facial manipulators in lying, other than inconsistencies in verbal/nonverbal messages even telling the truth, probably due to their difficulties to identify and express emotions

How do we comprehend linguistic and visual narratives? A study in children with typical development

The present study investigated the comprehension of narrative with reference to global coherence, i.e., the global representation of story meaning and connectedness, across two different expressive modalities: stories conveyed through written language and stories conveyed through sequences of images. Two cognitive abilities possibly underpinning such comprehension were assessed: Central Coherence (CC) and Theory of Mind (ToM). Two groups of children with typical development aged between 8.00 and 10.11 years were included in the study: 40 participants received the narrative comprehension task in the linguistic modality; 40 participants were administered the narrative comprehension task in the visual condition. Analyses revealed that a change in the expressive code used to convey narratives did not entail a change in the overall comprehension performance: children of the two groups performed similarly on the narrative task. As for the cognitive abilities, CC and ToM scores were positively correlated with narrative comprehension score only in the visual narrative comprehension task, and not in the linguistic one. Moreover, a regression analysis showed that, along with age, CC significantly predicted the visual narrative comprehension score. The implications of these results are discussed.(c) 2022 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Beneficial Effects of Polydeoxyribonucleotide (PDRN) in an In Vitro Model of Fuchs Endothelial Corneal Dystrophy

Fuchs endothelial corneal dystrophy (FECD) is a bilateral, hereditary syndrome characterized by progressive irreversible injury in the corneal endothelium; it is the most frequent cause for corneal transplantation worldwide. Oxidative stress induces the apoptosis of corneal endothelial cells (CECs), and has a crucial function in FECD pathogenesis. The stimulation of the adenosine A2A receptor (A2Ar) inhibits oxidative stress, reduces inflammation and modulates apoptosis. Poly-deoxyribonucleotide (PDRN) is a registered drug that acts through adenosine A2Ar. Thus, the goal of this study was to assess the effect of PDRN in an in vitro FECD model. Human Corneal Endothelial Cells (IHCE) were challenged with H2O2 (200 µM) alone or in combination with PDRN (100 µg/mL), PDRN plus ZM241385 (1 µM) as an A2Ar antagonist, and CGS21680 (1 µM) as a well-known A2Ar agonist. H2O2 reduced the cells’ viability and increased the expression of the pro-inflammatory markers NF-κB, IL-6, IL-1β, and TNF-α; by contrast, it decreased the expression of the anti-inflammatory IL-10. Moreover, the pro-apoptotic genes Bax, Caspase-3 and Caspase-8 were concurrently upregulated with a decrease of Bcl-2 expression. PDRN and CGS21680 reverted the negative effects of H2O2. Co-incubation with ZM241385 abolished the effects of PDRN, indicating that A2Ar is involved in the mode of action of PDRN. These data suggest that PDRN defends IHCE cells against H2O2-induced damage, potentially as a result of its antioxidant, anti-inflammatory and antiapoptotic properties, suggesting that PDRN could be used as an FECD therapy

Optimization clustering techniques on register unemployment data

An important strategy for data classification consists in organising data points in clusters. The k-means is a traditional optimisation method applied to cluster data points. Using a labour market database, aiming the segmentation of this market taking into account the heterogeneity resulting from different unemployment characteristics observed along the Portuguese geographical space, we suggest the application of an alternative method based on the computation of the dominant eigenvalue of a matrix related with the distance among data points. This approach presents results consistent with the results obtained by the k-means.info:eu-repo/semantics/publishedVersio

Endometrioid Cancer Associated With Endometriosis: From the Seed and Soil Theory to Clinical Practice

Endometriosis is a benign condition characterized by the presence of ectopic endometrial tissue. It is still debated whether endometriosis is a disease that can predispose to the pathogenesis of endometrial cancer outside the uterus. Deficiencies in mismatch repair (MMR) genes are a known risk factor for developing endometrioid cancer. Starting from two cases of patients with abnormal MMR endometrioid carcinoma of the uterus and synchronous endometrioid carcinoma in non-ovarian and ovarian endometriosis, we performed a somatic mutation profile and phylogenetic analysis of the lesions in order to identify if they were metastasis or primary de novo tumors. In the first case, we identified de novo activating mutations in PIK3CA and KRAS in endometrioid cancer lesions but not in endometriosis. Although the acquisition of a de novo mutation in ESR1 and a decrease in mutant allele fraction (MAF) from the endometrial tumor to the localizations in the endometriosis lesions, the clonal relationship was confirmed by the limited number of heteroplasmic mutations in D-loop mitochondrial DNA region. In the other case, the clonal behavior was demonstrated by the overlap of MAF at each site. Our data support the hypothesis of a retrograde dissemination of tumor cells, moving from the primary carcinoma in the endometrium to ectopic sites of endometriosis where localizations of tumor arise

Gaia data release 1: Principles of the photometric calibration of the G band

Context. Gaia is an ESA cornerstone mission launched on 19 December 2013 aiming to obtain the most complete and precise 3D map of our Galaxy by observing more than one billion sources. This paper is part of a series of documents explaining the data processing and its results for Gaia Data Release 1, focussing on the G band photometry. Aims. This paper describes the calibration model of the Gaia photometric passband for Gaia Data Release 1. Methods. The overall principle of splitting the process into internal and external calibrations is outlined. In the internal calibration, a self-consistent photometric system is generated. Then, the external calibration provides the link to the absolute photometric flux scales. Results. The Gaia photometric calibration pipeline explained here was applied to the first data release with good results. Details are given of the various calibration elements including the mathematical formulation of the models used and of the extraction and preparation of the required input parameters (e.g. colour terms). The external calibration in this first release provides the absolute zero point and photometric transformations from the Gaia G passband to other common photometric systems. Conclusions. This paper describes the photometric calibration implemented for the first Gaia data release and the instrumental effects taken into account. For this first release no aperture losses, radiation damage, and other second-order effects have not yet been implemented in the calibration.Comment: 15 pages, 16 figures, Gaia data release 1 documentation special volum

An asymmetric explosion as the origin of spectral evolution diversity in type Ia supernovae

Type Ia Supernovae (SNe Ia) form an observationally uniform class of stellar explosions, in that more luminous objects have smaller decline-rates. This one-parameter behavior allows SNe Ia to be calibrated as cosmological `standard candles', and led to the discovery of an accelerating Universe. Recent investigations, however, have revealed that the true nature of SNe Ia is more complicated. Theoretically, it has been suggested that the initial thermonuclear sparks are ignited at an offset from the centre of the white-dwarf (WD) progenitor, possibly as a result of convection before the explosion. Observationally, the diversity seen in the spectral evolution of SNe Ia beyond the luminosity decline-rate relation is an unresolved issue. Here we report that the spectral diversity is a consequence of random directions from which an asymmetric explosion is viewed. Our findings suggest that the spectral evolution diversity is no longer a concern in using SNe Ia as cosmological standard candles. Furthermore, this indicates that ignition at an offset from the centre of is a generic feature of SNe Ia.Comment: To appear in Nature, 1st July 2010 issue. 36 pages including supplementary materials. 4 figures, 3 supplementary figures, 1 supplementary tabl

SN 2003du: 480 days in the life of a normal type Ia supernova

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