Gal-1 and LAT1 as regulatory molecules in skin inflammatory diseases

Tesis Doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina. Departamento de Bioquímica. Fecha de Lectura: 15-07-2021Skin diseases are common disorders with a high prevalence among occupational diseases. Allergic contact dermatitis (ACD) and psoriasis are complex and frequent inflammatory skin pathologies in which the immune system and epithelial alterations play an important role in their development. ACD, also known as contact hypersensitivity (CHS), is a frequent T-cell mediated inflammatory skin disease characterized by red, itchy, swollen and cracked skin. It is caused by the direct contact with an allergen and/or irritant. Galectin-1 (Gal-1) is a β-galactoside-binding lectin which is highly expressed in several types of immune cells. The role of endogenous Gal-1 in CHS is not known. We found that Gal-1-deficient mice display more sustained and prolonged skin inflammation than wild-type mice after oxazolone treatment. Gal-1-deficient mice have increased CD8+ T cells and neutrophilic infiltration in the skin. After the sensitization phase, Gal-1-depleted mice showed increased frequency of central memory CD8+ T cells and IFNγ secretion by CD8+ T cells. The absence of Gal-1 does not affect migration of transferred CD4+ and CD8+ T cells from the blood to the lymph nodes or to the skin. Depletion of CD4+ T lymphocytes as well as adoptive transfer experiments demonstrated that endogenous expression of Gal-1 on CD8+ T lymphocytes exerts a major role in the control of CHS model. These data underscore the protective role of endogenous Gal-1 in CD8+ but not CD4+ T cells in the development of CHS disease. Psoriasis is a common chronic skin disorder characterized by a thickened epidermis caused by keratinocyte (KC) proliferation and dermal inflammatory infiltrate. The main clinical manifestation is the presence of raised, squamous, erythematous oval plaques. The progress of this pathology can be affected by diverse causes such as immune system, genetic, autoantigens and environmental factors. It is mainly mediated by IL-23, IL-1β, and IL-17. Although psoriasis is a hyperproliferative skin disorder, the possible role of amino acid transporters has remained unexplored. Thus, we sought to investigate the role of the essential amino acid transporter L-type amino acid transporter 1 (LAT1) in psoriasis. We found that LAT1 expression is increased in KCs and skin-infiltrating lymphocytes of psoriatic lesions in human subjects and mice. LAT1 deletion in KCs does not dampen the inflammatory response or their proliferation, which could be maintained by increased expression of the alternative amino acid transporters LAT2 and LAT3. Specific deletion of LAT1 in γδ and CD4+ T cells controls the inflammatory response induced by imiquimod (IMQ). LAT1 deletion or inhibition by JPH203 blocks expansion of IL-17-secreting γ4+δ4+ and CD4+ T cells and dampens the release of IL-1β, IL-17, and IL-22 in the IMQ-induced model. Moreover, inhibition of LAT1 blocks expansion of human γδ T cells and IL-17 secretion by human CD4+ T cells. IL-23 and IL-1β stimulation upregulates LAT1 expression and induces mTOR activation in IL-17+ γδ and Th17 cells. Deletion or inhibition of LAT1 efficiently controls IL-23-and IL-1β-induced phosphatidylinositol 3-kinase/AKT/mTOR activation independent of T-cell receptor signaling. Overall, this thesis work underscores the protective role of endogenous Gal-1 in CD8+ T cells in the development of CHS and the novel strategy to control skin inflammation in psoriasis mediated by the IL23/IL-1β/IL-17 axis through targeting LAT1-mediated amino acid upta

Methodology to Evaluate the State of Conservation of Historical Plasterwork and Its Polychrome to Promote Its Conservation

This research was funded by the I+D+i PGC2018-093470-B-I00 project financed by MCIN/AEI/10.13039/501100011033.This work presents a methodology for the assessment of ancient plasterworks based on traditional inspection techniques, such as organoleptic tests and chemical characterization, and also on digital tools, such as photogrammetric surveys, thermography images, and measurement of ambient conditions with thermohygrometers. This method allows not only defining the alterations detected and establishing the state of conservation but also digitalizing the plasterworks to preserve the heritage and replicate the model if necessary (i.e., replacement of a detachment piece), drawing a hypothesis of the original hidden design of the plasterwork, and conducting a chronological study about the polychromies used over time. In some cases, the assessment has shown that the liming and repolychrome interventions to which plasterworks have been subjected and the powdery state of some areas do not ensure the possibility of the complete polychromy restoration, only its preservation by taking conservation and maintenance measures.MCIN/AEI I+D+i PGC2018-093470-B-I0

Therapeutic Applications and Effects of Lupinus angustifolius (Blue Lupin) and Its Components: A Systematic Review and Meta-Analysis

Lupinus angustifolius has a unique nutrient profile among legumes and may have beneficial health effects when included in the diet. The aim of this study was to investigate the biological properties of blue lupin (Lupinus angustifolius), its chemical components, and their relevance for monitoring biological and anthropometric health markers, including triglycerides (TGs), low-density lipoprotein cholesterol (LDL-C), BMI, weight, and glycemia, compared with control groups with other kinds of diets. PubMed,Web of Science, and Scopus databases, updated to December 2023, were searched. Out of the 194 studies identified, a total of 7 randomized controlled trials (RCTs) comprising 302 participants met the eligibility criteria. The results of our study indicated that the blue lupin diet has a direct relationship with parameters such as blood glucose, weight, and LDL-C but not with TGs or BMI. In conclusion, the research described in this review clearly indicates that L. angustifolius may play an important role in the dietary prevention of hyperlipidemia and hypertension. Therefore, it would be highly advisable to increase its consumption in diets. However, further studies, ideally in humans, are required to truly establish L. angustifolius’s health-promoting properties

Difficulties that influence the English teaching learning process in Students of second year morning shift at the National Institute San Jorge in Terrabona- Matagalpa during the second semester of 2011

Nowadays, there are many difficulties in the English Teaching Learning Process (ETLP) in high school which restrain a satisfactory assimilation of English as a foreign language. These difficulties cover different aspects of the ETLP. This research talks about poor vocabulary, students’ misbehavior, lack of motivation, lack of dedication to study, and lack of interest in English class in second year at San Jorge Institute in Terrabona, during the second semester 2011. In this municipality no one had previously investigated the reasons why the high school students have many difficulties in learning English. To carry out this research, first of all it was observed that this group was achieving the lowest academic performance in San Jorge Institute and based on this observation, it was considered pertinent to make an intense analysis of this situation. The bibliography on this theme was read and then two surveys were applied, one survey for the teacher and one survey for the students and one guide for the observation. These instruments of investigation were based on some important aspects that the experts point out about onveying the ETLP, in order to get a satisfactory performance in the learning of a foreign language. After that, the information was processed and a statement was written about the information collected and the contribution of the scientific theory. It was considered important to research the difficulties of the English Teaching-Learning Process. The goal of all early language education should be to gaze students when they are young and keep them interested in learning English for the rest of their lives

Aplicación del modelo de Lewin a una OCS: cambio organizacional y liderazgo

Las Organizaciones de la Sociedad Civil (OSC), pequeñas, se caracterizan por problemas estructurales en su interior. En particular, muestran tanto dependencia de las decisiones del líder-fundador como resistencia al cambio, al influir en los niveles de eficiencia y responsabilidad de los colaboradores. Esta situación es de consideración mayor dado el rol que las OSC desempeñan en términos de desarrollo social. El objetivo del documento es analizar, por medio de las dos primeras etapas del modelo de cambio propuesto por Lewin, el proceso de transformación de una asociación civil en México. Para ello, se revisa la importancia teórica del líder-fundador y del cambio organizacional. Se describe brevemente la teoría del cambio de Lewin para identificar las fuerzas obstaculizadoras e impulsoras, así como las etapas de descongelamiento, cambio y recongelamiento en esta asociación. Se encuentra que el uso del modelo de Lewin permite reducir la resistencia al cambio a través de un plan que brinde certidumbre a quienes establecen el proyecto de cambio al generar mayor participación de los colaboradores mediante su empoderamiento.Small Civil Society Organizations (OSC) are characterized by structural problems within. Particularlly, they show a dependence of decisions made by the Leader-Founder and resistence to change, which impact on levels of eficiency and accountability of their collaborators. This situation is of major consideration given the role they play in terms of social development. The aim of the paper is to analyze, through the first two steps of the model of change proposed by Lewin, the process of change of a Mexican civil association. For doing that, the theoretically relevance of the leader-founder and of organizational change is reviewed. Also, Lewin´s theory of change is described in order to identify driving and restraining forces, as well as the stages of unfreeze, change and refreeze of this association. It is found that the use of Lewin´s model allows reducing resistence to change with a plan that provides certainty to those implementing the project of change by generating greater participation of its collaborators through their empowerment

Photoelectrochemical water splitting with ITO/WO3/BiVO4/CoPi multishell nanotubes fabricated by soft-templating in vacuum

A well-established procedure for the photoelectrochemical (PEC) splitting of water relies on using porous electrodes of WO3 sensitized with BiVO4 as a visible scavenger photoanode semiconductor. In this work, we propose an evolved photoelectrode fabricated by a soft-template approach consisting of supported multishell nanotubes (NTs). These NTs are formed by a concentric layered structure of indium tin oxide (ITO), WO3, and BiVO4, together with a final film of cobalt phosphate (CoPi) co-catalyst. Photoelectrode manufacturing is easily implemented at large scale and combines thermal evaporation of single crystalline organic nanowires (ONWs), magnetron sputtering (for ITO and WO3), solution dripping, and electrochemical deposition processes (for BiVO4 and CoPi, respectively) plus annealing under mild conditions. The obtained NT electrodes depict a large electrochemically active surface and outperform by more than one order of magnitude the efficiency of equivalent planar-layered electrodes. A thorough electrochemical analysis of the electrodes under blue and solar light illumination demonstrates the critical role of the WO3/BiVO4 Schottky barrier heterojunction in the control of the NT electrode efficiency and its dependence on the BiVO4 outer layer thickness. Oxygen evolution reaction (OER) performance was maximized with the CoPi electrocatalyst, rendering high photocurrents under one sun illumination. The reported results demonstrate the potential of the soft-template methodology for the large area fabrication of highly efficient multishell ITO/WO3/BiVO4/CoPi NT electrodes, or other alternative combinations, for the photoelectrochemical splitting of water.Comment: Manuscript: 39 pages, 8 figures and 1 table. SI: 15 pages, 9 figures and 1 tabl

DESPIDO OBJETIVO A CAUSA DE INCAPACIDAD TEMPORAL CUANDO HAY UNA DISCAPACIDAD

Analizare algunas cuestiones, en las que la procedencia del despido objetivo por causas como la “Ineptitud sobrevenida del trabajador”, o el “Absentismo” contempladas en el artículo 52 apartado a) y d) del Real Decreto Legislativo 2/2015, de 23 de octubre, por el que se aprueba el texto refundido de la Ley del Estatuto de los Trabajadores. Puede resultar algo confuso cuando hablamos de “DESPIDO OBJETIVO A CAUSA DE INCAPACIDAD TEMPORAL CUANDO HAY UNA DISCAPACIDAD”.<br /

The Minor Allele of rs7574865 in the STAT4 Gene Is Associated with Increased mRNA and Protein Expression

We studied 201 patients (80% female; median age, 54 years; median disease duration, 5.4 months) from PEARL study. Demographic, clinical, laboratory and therapeutic data were collected at each visit. IL-6 serum levels were measured by enzyme immune assay. The rs7574865 was genotyped using TaqMan probes. The expression levels of STAT4 mRNA were determined at 182 visits from 69 patients using quantitative real-time polymerase chain reaction. STAT4 protein was assessed by western blot in 62 samples from 34 patients. To determine the effect of different variables on the expression of STAT4 mRNA and protein, we performed multivariate longitudinal analyses using generalized linear models.This work was supported by grants awarded to IGA from the RETICS Program (RD08/0075/0004 and RD12/0009/0017 [RIER]) and FIS Program (PI11/0551) and to JM from RETICS Program (RD08/0075/0011 and RD12/0009/0004 [RIER]) from the Instituto de Salud Carlos III (www.isciii.es). Measurement of IL-6 levels described in this article was supported by different research grants from Roche to IGA. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewe