Deciphering GRINA/Lifeguard1: Nuclear Location, Ca2+ Homeostasis and Vesicle Transport

The Glutamate Receptor Ionotropic NMDA-Associated Protein 1 (GRINA) belongs to the Lifeguard family and is involved in calcium homeostasis, which governs key processes, such as cell survival or the release of neurotransmitters. GRINA is mainly associated with membranes of the endoplasmic reticulum, Golgi, endosome, and the cell surface, but its presence in the nucleus has not been explained yet. Here we dissect, with the help of different software tools, the potential roles of GRINA in the cell and how they may be altered in diseases, such as schizophrenia or celiac disease. We describe for the first time that the cytoplasmic N-terminal half of GRINA (which spans a Proline-rich domain) contains a potential DNA-binding sequence, in addition to cleavage target sites and probable PY-nuclear localization sequences, that may enable it to be released from the rest of the protein and enter the nucleus under suitable conditions, where it could participate in the transcription, alternative splicing, and mRNA export of a subset of genes likely involved in lipid and sterol synthesis, ribosome biogenesis, or cell cycle progression. To support these findings, we include additional evidence based on an exhaustive review of the literature and our preliminary data of the protein–protein interaction network of GRINA

Programa de intervención comunitaria para promover el autocuidado individual y familiar en el Caserío Bello Horizonte, Distrito de la Banda de Shilcayo-Región San Martín. Junio 2014 – Julio 2015

Con el objetivo de desarrollar y fortalecer las habilidades para promover el autocuidado de las familias del caserío de Bello Horizonte, distrito de la Banda de Shilcayo, Provincia y Región San Martín; se implementó un “Programa de intervención comunitaria para promover el autocuidado individual y familiar en Bello Horizonte. Junio 2014 – Julio 2015”. Primero se realizó un diagnóstico para identificar y priorizar la problemática. Luego se diseñó cuatro módulos con temas: higiene, manipulación de alimentos, consumo de agua segura, autoestima y comunicación, nutrición, salud reproductiva, anticonceptivos, derechos sexuales, interculturalidad, violencia y cultura de paz. Seguidamente se desarrolló el programa con 75 familias que voluntariamente decidieron participar; se ejecutó 12 talleres de capacitación y 8 visitas domiciliarias a cada familia, con pre y post medición. Resultados: Las prácticas de higiene: tratamiento de agua para beber, acumulación y eliminación de basura, muestran una diferencia significativa (P<0.005); los conocimientos de las familias a pesar de evidenciar mejoras en la evaluación de salida en todos los ítems evaluados, sólo la enfermedades que produce la basura muestra diferencia significativa (p<0.05); la mayoría aprendió a lavarse las manos con agua y jabón en momentos críticos (p<0.05); todos los estilos de vida, la resolución de conflictos y la tenencia de normas de convivencia muestran diferencia significativa (p<0.05); los indicadores referenciales de la Red de Salud de San Martin son halagadores. La metodología aplicada y validada en el programa condicionó estos resultados. En conclusión el programa ha permitido cambios significativos de comportamiento sobre el cuidado de la salud.With the objective of developing and strengthening the skills to promote self-care of the families of the Bello Horizonte, district Banda of Shilcayo, San Martín Province and Region; a "Community intervention program to promote individual and family self-care in Bello Horizonte was implemented. June 2014 - July 2015 ". First, a diagnosis was made to identify and prioritize the problem. Then four modules were designed with themes: hygiene, food manipulation, safe water consumption, self-esteem and communication, nutrition, reproductive health, contraceptives, sexual rights, interculturality, violence and culture of peace. Then the program was developed with 75 families who voluntarily decided to participate; 12 training workshops were carried out and 8 home visits to each family, with pre- and post-measurement. Results: Hygienic practices: water treatment for drinking, accumulation and elimination of garbage, show a significant difference (P <0.005); the knowledge of the families in spite of evidencing improvements in the exit evaluation in all the evaluated items, only the diseases produced by the garbage show significant difference (p <0.05); most learned to wash their hands with soap and water at critical times (p <0.05); all lifestyles, conflict resolution and cohabitation rules show significant difference (p <0.05); The benchmarks of the San Martin Health Network are flattering. The methodology applied and validated in the program conditioned these results. In conclusion, the program has allowed significant changes in behavior regarding health care. In conclusion, the program has allowed significant changes in behavior regarding health care.Trabajo de investigaciónVancouve

Cannabinoid receptor CB2 drives HER2 pro-oncogenic signaling in breast cancer

Pharmacological activation of cannabinoid receptors elicits antitumoral responses in different models of cancer. However, the biological role of these receptors in tumor physio-pathology is still unknown. We analyzed CB2 cannabinoid receptor protein expression in two series of 166 and 483 breast tumor samples operated in the University Hospitals of Kiel, Tübingen and Freiburg between 1997 and 2010. CB2 mRNA expression was also analyzed in previously published DNA microarray datasets. The role of CB2 in oncogenesis was studied by generating a mouse line that expresses the HER2 rat ortholog (neu) and lacks CB2, and by a variety of biochemical and cell biology approaches in human breast cancer cells in culture and in vivo, upon modulation of CB2 expression by si/shRNAs and overexpression plasmids. CB2-HER2 molecular interaction was studied by co-localization, coimmunoprecipitation and proximity ligation assays. We show an association between elevated CB2 expression in HER2+ breast tumors and poor patient prognosis. We also demonstrate that genetic inactivation of CB2 impairs tumor generation and progression in MMTV-neu mice. Moreover, we show that HER2 upregulates CB2 expression by activating the transcription factor ELK1 via the ERK cascade, and that an increased CB2 expression activates the HER2 prooncogenic signaling machinery at the level of the tyrosine kinase c-SRC. Finally, HER2 and CB2 form heteromers in cancer cells. Our findings reveal an unprecedented role of CB2 as a pivotal regulator of HER2 pro-oncogenic signaling in breast cancer, and suggest that CB2 may be a biomarker with prognostic value in these tumors

Differentially Deregulated MicroRNAs as Novel Biomarkers for Neoplastic Progression in Ulcerative Colitis.

INTRODUCTION: Colorectal cancer (CRC) is a potentially life-threatening complication of long-standing ulcerative colitis (UC). MicroRNAs (miRNA) are epigenetic regulators that have been involved in the development of UC-associated CRC. However, their role as potential mucosal biomarkers of neoplastic progression has not been adequately studied. METHODS: In this study, we analyzed the expression of 96 preselected miRNAs in human formalin-fixed and paraffin-embedded tissue of 52 case biopsies (20 normal mucosa, 20 dysplasia, and 12 UC-associated CRCs) and 50 control biopsies (10 normal mucosa, 21 sporadic adenomas, and 19 sporadic CRCs) by using Custom TaqMan Array Cards. For validation of deregulated miRNAs, we performed individual quantitative real-time polymerase chain reaction in an independent cohort of 50 cases (13 normal mucosa, 25 dysplasia, and 12 UC-associated CRCs) and 46 controls (7 normal mucosa, 19 sporadic adenomas, and 20 sporadic CRCs). RESULTS: Sixty-four miRNAs were found to be differentially deregulated in the UC-associated CRC sequence. Eight of these miRNAs were chosen for further validation. We confirmed miR-31, -106a, and -135b to be significantly deregulated between normal mucosa and dysplasia, as well as across the UC-associated CRC sequence (all P < 0.01). Notably, these miRNAs also confirmed to have a significant differential expression compared with sporadic CRC (all P < 0.05). DISCUSSION: UC-associated and sporadic CRCs have distinct miRNA expression patterns, and some miRNAs indicate early neoplastic progression.This work was funded by grants from the Instituto de Salud Carlos III (PI12/01481; PI19/01050). Project PI19/ 01050 is funded by Instituto de Salud Carlos III (ISCIII) and co funded by the European Union. CIBEREHD is funded by the Insti tuto de Salud Carlos III and Beca Marató de TV3 (201932-30). Parts of this work were also supported by the Xarxa de Bancs de Tumors de Catalunya sponsored by Pla Director d’Oncología de Catalunya (XBTC) and by the Hospital Clínics Premi Fi de Residència (G.J). None of the funding parties has been involved in collection, analysis, and interpretation of the data

Stepwise strategy based on 1H-NMR fingerprinting in combination with chemometrics to determine the content of vegetable oils in olive oil mixtures

1H NMR fingerprinting of edible oils and a set of multivariate classification and regression models organised in a decision tree is proposed as a stepwise strategy to assure the authenticity and traceability of olive oils and their declared blends with other vegetable oils (VOs). Oils of the 'virgin olive oil' and 'olive oil' categories and their mixtures with the most common VOs, i.e. sunflower, high oleic sunflower, hazelnut, avocado, soybean, corn, refined palm olein and desterolized high oleic sunflower oils, were studied. Partial least squares (PLS) discriminant analysis provided stable and robust binary classification models to identify the olive oil type and the VO in the blend. PLS regression afforded models with excellent precisions and acceptable accuracies to determine the percentage of VO in the mixture. The satisfactory performance of this approach, tested with blind samples, confirm its potential to support regulations and control bodies. Keywords: Adulteration; Authentication; Decision tree; Multivariate data analysis; Nuclear magnetic resonance; Olive oil

Differentially Deregulated MicroRNAs as Novel Biomarkers for Neoplastic Progression in Ulcerative Colitis

Introduction: Colorectal cancer (CRC) is a potentially life-threatening complication of long-standing ulcerative colitis (UC). MicroRNAs (miRNA) are epigenetic regulators that have been involved in the development of UC-associated CRC. However, their role as potential mucosal biomarkers of neoplastic progression has not been adequately studied. Methods: In this study, we analyzed the expression of 96 preselected miRNAs in human formalin-fixed and paraffin-embedded tissue of 52 case biopsies (20 normal mucosa, 20 dysplasia, and 12 UC-associated CRCs) and 50 control biopsies (10 normal mucosa, 21 sporadic adenomas, and 19 sporadic CRCs) by using Custom TaqMan Array Cards. For validation of deregulated miRNAs, we performed individual quantitative real-time polymerase chain reaction in an independent cohort of 50 cases (13 normal mucosa, 25 dysplasia, and 12 UC-associated CRCs) and 46 controls (7 normal mucosa, 19 sporadic adenomas, and 20 sporadic CRCs). Results: Sixty-four miRNAs were found to be differentially deregulated in the UC-associated CRC sequence. Eight of these miRNAs were chosen for further validation. We confirmed miR-31, -106a, and -135b to be significantly deregulated between normal mucosa and dysplasia, as well as across the UC-associated CRC sequence (all P < 0.01). Notably, these miRNAs also confirmed to have a significant differential expression compared with sporadic CRC (all P < 0.05). Discussion: UC-associated and sporadic CRCs have distinct miRNA expression patterns, and some miRNAs indicate early neoplastic progression

Determination of Vegetable Oils in Olive Oil Mixtures Using a Stepwise Strategy Based on H-1-Nmr Fingerprinting and Pattern Recognition

Final version is available in open access in publisher’s site.-- This abstract is based on the published article: Rosa María Alonso-Salces, Luis Ángel Berrueta, Beatriz Quintanilla-Casas, Stefania Vichi, Alba Tres, María Isabel Collado, Carlos Asensio-Regalado, Gabriela Elena Viacava, Aimará Ayelen Poliero, Enrico Valli, Alessandra Bendini, Tullia Gallina Toschi, José Manuel Martínez-Rivas, Wenceslao Moreda, Blanca Gallo. Stepwise strategy based on 1H-NMR fingerprinting in combination with chemometrics to determine the content of vegetable oils in olive oil mixtures. Food Chemistry, Volume 366, 2022, 130588, https://doi.org/10.1016/j.foodchem.2021.130588.--http://hdl.handle.net/10261/261907Peer reviewe

Comunicación 6 : cuaderno de autoaprendizaje

Cuaderno de autoaprendizaje del área de Comunicación para el ciclo V. Este texto está conformado por ocho unidades, en las cuales los estudiantes encontrarán diversas actividades que los ayudarán a aprender y desarrollar sus conocimientos en el área

Comunicación 6to. grado : cuaderno de autoaprendizaje

Este cuaderno de autoaprendizaje ha sido preparado para ti con mucho cariño y dedicación por un equipo de profesoras y profesores. Su objetivo es brindarte la oportunidad de aprender a comunicarte a través de diversas situaciones retadoras, relacionadas con actividades socioproductivas de los diversos departamentos de nuestro país. Este cuaderno de autoaprendizaje está formado por ocho unidades. En cada una de ellas se plantean dos actividades retadoras que te permitirán dialogar, leer, escribir y expresarte sobre diversos temas. Además, encontrarás cuentos, poemas, adivinanzas, rimas, trabalenguas, canciones, afiches y otras expresiones literarias