Molecular mechanism of influenza A NS1-mediated TRIM25 recognition and inhibition

RIG-I is a viral RNA sensor that induces the production of type I interferon (IFN) in response to infection with a variety of viruses. Modification of RIG-I with K63-linked poly-ubiquitin chains, synthesised by TRIM25, is crucial for activation of the RIG-I/MAVS signalling pathway. TRIM25 activity is targeted by influenza A virus non-structural protein 1 (NS1) to suppress IFN production and prevent an efficient host immune response. Here we present structures of the human TRIM25 coiled-coil-PRYSPRY module and of complexes between the TRIM25 coiled-coil domain and NS1. These structures show that binding of NS1 interferes with the correct positioning of the PRYSPRY domain of TRIM25 required for substrate ubiquitination and provide a mechanistic explanation for how NS1 suppresses RIG-I ubiquitination and hence downstream signalling. In contrast, the formation of unanchored K63-linked poly-ubiquitin chains is unchanged by NS1 binding, indicating that RING dimerisation of TRIM25 is not affected by NS1

Worries, mental and emotional health difficulties of portuguese university students

Copyright © Society for Science and Education, United KingdomThe aim of this study was to reach an in-depth understanding on how Portuguese university students feel towards life in general, which are their worries, how often they feel worried, and how intense their worries are. Moreover, it was intended to identify the kind of psychosocial variables involved, strategies they use as well as which are the sources of their well-being. A total of 2991 university students, participated in the quantitative study and in the qualitative study, there were 50 participants between 18 and 35 years old. A significant minority of students got worried frequently, allowing their worries to interfere significantly in their lives. Gender and age differences were found. Having worries demonstrated to be relevant and negatively associated with young people’s perception of well-being, self-regulation and resilience; showing that the mental health of the Portuguese university students is at risk, mainly when their social emotional skills are underdeveloped.Foundation for Science and Technology (FCT) (Grants: Marta Reis-SFRH/BPD/110905/2015)info:eu-repo/semantics/publishedVersio

Positive youth development : interactions between healthy lifestyle behaviours and psychosocial variables

Copyright © 2006 - 2018 The Canadian Center of Science and Education. All Rights Reserved .Copyright for this article is retained by the author(s), with first publication rights granted to the journal. This is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).The Positive Youth Development - PYD concept emphasised the importance of strengthening developmental assets in youth’s networks and contexts. This paper examines the correlation between PYD, healthy lifestyle behaviours and psychosocial variables (self-regulation, resilience, and anxiety); and the impact of PYD and psychosocial variables on healthy lifestyle behaviours. 2700 youths (73.3% girls; mean age 21.3±2.79 years) were included. Results showed that all variables mostly had significantly correlational associations. Specifically, the linear regression model evidenced that the promotion of PYD and self-regulation, along with the reduction of anxiety can be relevant for improving healthy lifestyle behaviours. Such results suggest a dynamic interdependence between all the present variables, reinforcing the need to study positive indicators for youth development. Having more knowledge in this area can help health professionals, educators, and policy-makers, in order to better plan interventions/policies and to improve an integral healthy perspective for youths, based on interdisciplinary and transdisciplinary work.info:eu-repo/semantics/publishedVersio

Understanding consumer acceptability of verjuice, its potential applications and sensory and chemical drivers of liking

The wine sector is working to add value, enhance sustainability and reduce waste, yet often creating new products with unknown consumer acceptance. Verjuice, juice made from discarded unripe thinned grapes, is an example. Whilst verjuice has various culinary uses, its versatility in beverages continues to expand. However, its sensory drivers of liking when consumed as a drink, and their potential impact on its application remain unclear. Chemical drivers of sensory characteristics are also unknown representing a critical knowledge gap needed to guide product innovation. This study aimed to provide new knowledge regarding consumer acceptability of verjuice by identifying its sensory drivers of liking as a beverage, evaluating its potential use in different applications and identifying chemical drivers of its sensory characteristics. New Zealand consumers (n = 93) evaluated 13 verjuice samples from different countries. Furthermore, verjuice familiarity and its influence on emotional response was investigated to determine likely future consumer engagement. Sweetness was the most positive driver of liking in verjuice overall, followed by fruity and floral notes, smoothness, and to a lesser extent citrus flavour. Consumers expressed varied preferences for verjuice’s sensory profile, with fruity, floral, and honey flavours driving beverage application, whilst winey and green apple notes were more associated with culinary scenarios. Some association between chemical parameters and sensory attributes were evident (e.g. sugars were highly associated with perceived sweetness, fruity, and floral attributes; these attributes also shared proximity with 1-hexanol and cyclohexanol). The general idea of verjuice elicited positive valence emotions, but consumers who were ‘not familiar’ felt more curious, and those ‘familiar’ felt happier and more satisfied. Findings highlight the potential to tailor verjuice for specific applications by understanding desired sensory profiles and related chemical parameters. Recognising the interplay between familiarity level and emotional response is crucial for positioning the product in the marketplace and fostering consumer engagement. Marketing initiatives are needed to increase verjuice familiarity and support product innovation, leading to increased product appeal.fals

Alienation and health in adolescents : an original evaluation tool

Copyright © 2018 by authors and Open Access Library Inc. This work is licensed under the Creative Commons Attribution International License (CC BY 4.0).The present work aims to construct and validate a tool enabling to evaluate alienation in Portuguese adolescents. Participants were a group of adolescents that participated in the Portuguese survey of the European study Health Behaviour in School-aged Children (HBSC). For this study, only adolescents from the 8th and 10th grades were included in the sample, comprising 3869 students. The results show a good adequacy of the confirmatory factorial analysis (CFA) model. This model revealed 3 subscales proposals—Demotivation, Isolation and Instability, and a full scale—Total Alienation. When analyzed in relation to other variables (gender, grade, wellbeing indicator and risk indicator), the alienation subscales showed an association between alienation and risk. These results are consistent with other studies about alienation which emphasizes that having good social relationships is associated with higher levels of wellbeing and quality of life and less involvement in risk behaviours by young peopleinfo:eu-repo/semantics/publishedVersio

Transcription of toll-like receptors 2, 3, 4 and 9, FoxP3 and Th17 cytokines in a susceptible experimental model of canine Leishmania infantum infection

Canine leishmaniosis (CanL) due to Leishmania infantum is a chronic zoonotic systemic disease resulting from complex interactions between protozoa and the canine immune system. Toll-like receptors (TLRs) are essential components of the innate immune system and facilitate the early detection of many infections. However, the role of TLRs in CanL remains unknown and information describing TLR transcription during infection is extremely scarce. The aim of this research project was to investigate the impact of L. infantum infection on canine TLR transcription using a susceptible model. The objectives of this study were to evaluate transcription of TLRs 2, 3, 4 and 9 by means of quantitative reverse transcription polymerase chain reaction (qRT-PCR) in skin, spleen, lymph node and liver in the presence or absence of experimental L. infantum infection in Beagle dogs. These findings were compared with clinical and serological data, parasite densities in infected tissues and transcription of IL-17, IL-22 and FoxP3 in different tissues in non-infected dogs (n = 10), and at six months (n = 24) and 15 months (n = 7) post infection. Results revealed significant down regulation of transcription with disease progression in lymph node samples for TLR3, TLR4, TLR9, IL-17, IL-22 and FoxP3. In spleen samples, significant down regulation of transcription was seen in TLR4 and IL-22 when both infected groups were compared with controls. In liver samples, down regulation of transcription was evident with disease progression for IL-22. In the skin, upregulation was seen only for TLR9 and FoxP3 in the early stages of infection. Subtle changes or down regulation in TLR transcription, Th17 cytokines and FoxP3 are indicative of the silent establishment of infection that Leishmania is renowned for. These observations provide new insights about TLR transcription, Th17 cytokines and Foxp3 in the liver, spleen, lymph node and skin in CanL and highlight possible markers of disease susceptibility in this model

Monocarboxylate transporter 4 (MCT4) and CD147 overexpression is associated with poor prognosis in prostate cancer

BACKGROUND. Monocarboxylate transporters (MCTs) are transmembrane proteins involved in the transport of monocarboxylates across the plasma membrane, which appear to play an important role in solid tumours, however the role of MCTs in prostate cancer is largely unknown.The aim of the present work was to evaluate the clinico-pathological value of monocarboxylate transporters (MCTs) expression, namely MCT1, MCT2 and MCT4, together with CD147 and gp70 as MCT1/4 and MCT2 chaperones, respectively, in prostate carcinoma. METHODS. Prostate tissues were obtained from 171 patients, who performed radical prostatectomy and 14 patients who performed cystoprostatectomy. Samples and clinico-pathological data were retrieved and organized into tissue microarray (TMAs) blocks. Protein expression was evaluated by immunohistochemistry in neoplastic (n= 171), adjacent non-neoplastic tissues (n= 135), PIN lesions (n=40) and normal prostatic tissue (n=14). Protein expression was correlated with patients' clinicopathologic characteristics. RESULTS. In the present study, a significant increase of MCT2 and MCT4 expression in the cytoplasm of tumour cells and a significant decrease in both MCT1 and CD147 expression in prostate tumour cells was observed when compared to normal tissue. All MCT isoforms and CD147 were expressed in PIN lesions. Importantly, for MCT2 and MCT4 the expression levels in PIN lesions were between normal and tumour tissue, which might indicate a role for these MCTs in the malignant transformation. Associations were found between MCT1, MCT4 and CD147 expressions and poor prognosis markers; importantly MCT4 and CD147 overexpression correlated with higher PSA levels, Gleason score and pT stage, as well as with perineural invasion and biochemical recurrence. CONCLUSIONS. Our data provides novel evidence for the involvement of MCTs in prostate cancer. According to our results, we consider that MCT2 should be further explored as tumour marker and both MCT4 and CD147 as markers of poor prognosis in prostate cancer.NPG, CP and VMG received fellowships from the Portuguese Foundation for Science and Technology (FCT), refs. SFRH/BD/61027/2009, SFRH/BPD/69479/ 2010 and SFRH/BI/33503/2008, respectively. This work was supported by the FCT grant ref. PTDC/SAU-FCF/104347/2008, under the scope of Programa Operacional Temático Factores de Competitividade” (COMPETE) of Quadro Comunitário de Apoio III and co-financed by Fundo Comunitário Europeu FEDER

Mental health promotion in school context : validation of the ES’COOL scale for teachers

Copyright: © Tomé G (2018). This Article is distributed under the terms of Creative Commons Attribution 4.0 International License.Introduction: In general, a large proportion of young people report themselves as healthy, happy and satisfied with their circumstances. However, it was estimated that about 20%of youths experience significant stress at times, which raised concerns about the long-term impact of this distress on future adjustment. However, there is evidence that only a small proportion of young people with disorders receive treatment, and that their personal distress is steadily linked to negative outcomes at school and to overall maladjustment ...info:eu-repo/semantics/publishedVersio

Understanding the chronology and occupation dynamics of oversized pit houses in the southern Brazilian highlands

A long held view about the occupation of southern proto-Je pit house villages of the southern Brazilian highlands is that these sites represent cycles of long-term abandonment and reoccupation. However, this assumption is based on an insufficient number of radiocarbon dates for individual pit houses. To address this problem, we conducted a programme of comprehensive AMS radiocarbon dating and Bayesian modelling at the deeply stratified oversized pit Houe 1, Baggio 1 site (Cal. A.D. 1395-1650), Campo Belo do Sul, Santa Catarina, Brazil. The straigraphy of House 1 revealed an unparalleled sequence of twelve well preserved floors evidencing a major change in occupation dynamics including five completely burnt collapsed roofs. The results of the radiocarbon dating allowed us to understand for the first time the occupation dynamics of an oversized pit house in the southern Brazilian highlands. The Bayesian model demonstrates that House 1 was occupied for over two centuries with no evidence of major periods of abandonment, calling into question previous models of long-term abandonment. In addition, the House 1 sequence allowed us to tie transformations in ceramic style and lithic technology to an absolute chronology. Finally, we can provide new evidence that the emergence of oversized domestic structures is a relatively recent phenomenon among the southern proto-Je. As monumental pit houses start to be bulit, small pit houses continue to be inhabited, evidencing emerging disparities in domestic architecture after AD 1000. Our research shows the importance of programmes of intensive dating of individual structures to understand occupation dynamcis and site permanence, and challenges long held assumptions that the southern Brazilian highlands were home to marginal cultures in the context of lowland South America