TXNDC5, a newly discovered disulfide isomerase with a key role in cell physiology and pathology

Thioredoxin domain-containing 5 (TXNDC5) is a member of the protein disulfide isomerase family, acting as a chaperone of endoplasmic reticulum under not fully characterized conditions As a result, TXNDC5 interacts with many cell proteins, contributing to their proper folding and correct formation of disulfide bonds through its thioredoxin domains. Moreover, it can also work as an electron transfer reaction, recovering the functional isoform of other protein disulfide isomerases, replacing reduced glutathione in its role. Finally, it also acts as a cellular adapter, interacting with the N-terminal domain of adiponectin receptor. As can be inferred from all these functions, TXNDC5 plays an important role in cell physiology; therefore, dysregulation of its expression is associated with oxidative stress, cell ageing and a large range of pathologies such as arthritis, cancer, diabetes, neurodegenerative diseases, vitiligo and virus infections. Its implication in all these important diseases has made TXNDC5 a susceptible biomarker or even a potential pharmacological target

Listeria monocytogenes Inhibits Serotonin Transporter in Human Intestinal Caco-2 Ce

Listeria monocytogenes is a Gram-positive bacterium that can cause a serious infection. Intestinal microorganisms have been demonstrated to contribute to intestinal physiology not only through immunological responses but also by modulating the intestinal serotonergic system. Serotonin (5- HT) is a neuromodulator that is synthesized in the intestinal epithelium and regulates the whole intestinal physiology. The serotonin transporter (SERT), located in enterocytes, controls intestinal 5-HT availability and therefore serotonin’s effects. Infections caused by L. monocytogenes are well described as being due to the invasion of intestinal epithelial cells; however, the effect of L. monocytogenes on the intestinal epithelium remains unknown. The main aim of this work, therefore, was to study the effect of L. monocytogenes on SERT. Caco2/TC7 cell line was used as an enterocyte-like in vitro model, and SERT functional and molecular expression assays were performed. Our results demonstrate that living L. monocytogenes inhibits serotonin uptake by reducing SERT expression at the brush border membrane. However, neither inactivated L. monocytogenes nor soluble metabolites were able to affect SERT. The results also demonstrate that L. monocytogenes yields TLR2 and TLR10 transcriptional changes in intestinal epithelial cells and suggest that TLR10 is potentially involved in the inhibitory effect observed on SERT. Therefore, L. monocytogenes, through TLR10-mediated SERT inhibition, may induce increased intestinal serotonin availability and potentially contributing to intestinal physiological changes and the initiation of the inflammatory response.This work was funded by grants from the Spanish Ministry of Science and Innovation and the European Regional Development Fund (ERDF/FEDER) (BFU2010-18971), Zaragoza University (UZ2014- BIO-03), European Social Found (ESF), and the Aragon Regional Government (B61) and the Foundation for the Study of Inflammatory Bowel Diseases in Aragón (ARAINF 2012/0567). E. Latorre and E. Layunta are PhD student fellows from Aragon Regional Government (B105/11 and B022/13)

Aportación metodológica para determinar el índice de calidad del medio ambiente urbano y edificado del Área Metropolitana de Barcelona

El presente trabajo está orientado hacia la determinación de una metodología que evalúa características socio-residenciales, diagnostica el estado de bienestar del medio ambiente urbano del Área Metropolitana de Barcelona (AMB), responde al estado en que se encuentran las viviendas pre-existentes al 2001. La investigación incorpora una aportación al enfoque de valoración inmobiliaria sustentada en técnicas de valores sociales como parte de un contexto integral. La orientación al desarrollo sostenible constituye dar un enfoque de valoración inmobiliaria, es decir, retomando el valor de uso como una combinación de valores urbanos y de satisfacción residencial en la base del análisis. La hipótesis de la investigación nace a partir de desarrollar una metodología sustentada en indicadores parciales (simples) idóneos para la obtención del Índice de Calidad Edificada del AMB obtenido por el método del indicador sintético de distancia DP2. El objetivo de la investigación es demostrar la validación del método del indicador sintético de distancia.This work is oriented towards the determination of a methodology to assess socio-residential characteristics, diagnoses the welfare state of the urban environment in the metropolitan area of Barcelona (AMB), responds to the state that are pre-existing dwellings to 2001 . The research incorporates a contribution to real estate valuation approach supported by techniques of social values as part of a comprehensive context. The sustainable development orientation is an approach to property valuation, returning the value in use as a combination of urban values and residential satisfaction in the analysis. The hypothesis of the research stems from developing a methodology supported by partial indicators (simple) suitable for obtaining Built Quality Index of AMB obtained by the method of the synthetic indicator DP2 away. The objective of this research is to demonstrate the validation of the method of the synthetic indicator away.Peer Reviewe

A randomized, double blind, cross-over, placebo-controlled clinical trial to assess the effects of Candesartan on the insulin sensitivity on non diabetic, non hypertense subjects with dysglyce mia and abdominal obesity. "ARAMIA"

BACKGROUND: The raising prevalence of type-2 diabetes mellitus and obesity has been recognized as a major problem for public health, affecting both developed and developing countries. Impaired fasting plasma glucose has been previously associated with endothelial dysfunction, higher levels of inflammatory markers and increased risk of developing insulin resistance and cardiovascular events. Besides life-style changes, the blockade of the renin-angiotensin system has been proposed as a useful alternative intervention to improve insulin resistance and decrease the number of new type-2 diabetes cases. The aim of this clinical trial is to study the effect of the treatment with Candesartan, an angiotensin II receptor antagonist, on the insulin resistance, the plasma levels of adipoquines, oxidative stress and prothrombotic markers, in a group of non diabetic, non hypertensive, dysglycemic and obese subjects. METHODS AND DESIGN: A randomized, double blind, cross-over, placebo-controlled, clinical trial was designed to assess the effects of Candesartan (up to 32 mg/day during 6 months) on the Homeostasis Model Assessment (HOMA) index, lipid profile, protrombotic state, oxidative stress and plasma levels of inflammatory markers. The participants will be recruited in the "Fundación Cardiovascular de Colombia". Subjects who fullfil selection criteria will receive permanent educational, nutritional and exercise support during their participation in the study. After a 15 days-run-in period with placebo and life-style recommendations, the patients who have a treatment compliance equal or greater than 80% will be randomlly assigned to one of the treatment groups. Group A will receive Candesartan during 6 months and placebo during 6 months. Group B will receive placebo during the first 6 months, and then, Candesartan during the last 6 months. Control visits will be programed monthly and all parameters of interest will be evaluated every 6 months. HYPOTHESIS: Treatment with Candesartan, could improve the HOMA index, the response to the oral glucose tolerance test and reduce the plasma levels of adipoquines, oxidative stress and prothrombotic markers, in non diabetic, non hypertense subjects with dysglycemia and abdominal obesity, recruited from a population at high risk of developing insulin resistance. These effects are independent of the changes in arterial blood pressure. Trial registration: NCT0031920

RET signalling provides tumorigenic mechanism and tissue specificity for AIP-related somatotrophinomas

International audienceIt is unclear how loss-of-function germline mutations in the widely-expressed co-chaperone AIP , result in young-onset growth hormone secreting pituitary tumours. The RET receptor, uniquely co-expressed in somatotrophs with PIT1, induces apoptosis when unliganded, while RET supports cell survival when it is bound to its ligand. We demonstrate that at the plasma membrane, AIP is required to form a complex with monomeric-intracellular-RET, caspase-3 and PKCδ resulting in PIT1/CDKN2A-ARF/p53-apoptosis pathway activation. AIP-deficiency blocks RET/caspase-3/PKCδ activation preventing PIT1 accumulation and apoptosis. The presence or lack of the inhibitory effect on RET-induced apoptosis separated pathogenic AIP variants from non-pathogenic ones. We used virogenomics in neonatal rats to demonstrate the effect of mutant AIP protein on the RET apoptotic pathway in vivo. In adult male rats altered AIP induces elevated IGF-1 and gigantism, with pituitary hyperplasia through blocking the RET-apoptotic pathway. In females, pituitary hyperplasia is induced but IGF-1 rise and gigantism are blunted by puberty. Somatotroph adenomas from pituitary-specific Aip -knockout mice overexpress the RET-ligand GDNF, therefore, upregulating the survival pathway. Somatotroph adenomas from patients with or without AIP mutation abundantly express GDNF, but AIP -mutated tissues have less CDKN2A-ARF expression. Our findings explain the tissue-specific mechanism of AIP-induced somatotrophinomas and provide a previously unknown tumorigenic mechanism, opening treatment avenues for AIP -related tumours

Internet of things

Manual of Digital Earth / Editors: Huadong Guo, Michael F. Goodchild, Alessandro Annoni .- Springer, 2020 .- ISBN: 978-981-32-9915-3Digital Earth was born with the aim of replicating the real world within the digital world. Many efforts have been made to observe and sense the Earth, both from space (remote sensing) and by using in situ sensors. Focusing on the latter, advances in Digital Earth have established vital bridges to exploit these sensors and their networks by taking location as a key element. The current era of connectivity envisions that everything is connected to everything. The concept of the Internet of Things(IoT)emergedasaholisticproposaltoenableanecosystemofvaried,heterogeneous networked objects and devices to speak to and interact with each other. To make the IoT ecosystem a reality, it is necessary to understand the electronic components, communication protocols, real-time analysis techniques, and the location of the objects and devices. The IoT ecosystem and the Digital Earth (DE) jointly form interrelated infrastructures for addressing today’s pressing issues and complex challenges. In this chapter, we explore the synergies and frictions in establishing an efficient and permanent collaboration between the two infrastructures, in order to adequately address multidisciplinary and increasingly complex real-world problems. Although there are still some pending issues, the identified synergies generate optimism for a true collaboration between the Internet of Things and the Digital Earth

Latest language policy proposals in education in the Valencian Country

15th International Conference of the Spanish Association of Language and Literature Education, 15th International Conference SEDLL, 19-21 November 2014, Valencia, SpainIn this paper, the language policy proposals included in the election programmes of the political parties and coalitions which obtained representation in the Valencian Parliament after the 2011 May elections are analysed. Their consistency and coherence is studied from a sociolinguistic perspective. From a critical discourse analysis perspective, these sets of proposals are compared to the language perception which appears in them. The comparison of the proposals of the different groups represented in the Parliament complements the study of the past and present Valencian language policy. Although the real possibilities to access the government of the different parties are not analysed, by including the parties which now represent the government and the opposition, the maximum and minimum threshold for language policy development in the mid-term are established. To analyse the Valencian language policy, it is necessary to consider Spanish, the other official language and common to the rest of the Spanish state, and see whether there are direct or implicit references to it. Regarding the educational environment, the presence of English and its importance in the school curricula in a generalised discourse context which advocates for its learning can be determining in the design and use of the teaching languages in the Valencian educational system.Mas Castells, JA.; Mestre-Mestre, EM. (2015). Latest language policy proposals in education in the Valencian Country. Procedia Social and Behavioral Sciences. 178:151-156. doi:10.1016/j.sbspro.2015.03.172S15115617