Contextualización de la Agricultura y el Patrimonio a miras de Identificar y Caracterizar Productos de Interés Patrimonial/Contextualization of Agriculture and Heritage in order to Identify and Characterize Products of Patrimonial Interest

El Gobierno Provincial de Chimborazo contó con un proceso enriquecedor y participativo de alrededor de tres años que devino en la construcción de una Agenda De Competitividad, la misma que marca una línea de proyección para el fomento productivo de la Provincia de Chimborazo. Dentro de una lectura de estrategias agrícolas, se precisaron un conjunto de productos con una profunda relación social, pero que presentan serias debilidades en términos de productividad y posibilidades de mercado, como por ejemplo diversas variedades tubérculos andinos, o ciertas gramíneas, empero no por ello hay que extralimitar estos cultivos frente al desarrollo, al contrario, en función de la sostenibilidad son una prioridad de rescatar, mantener y valorizar. El objetivo de este trabajo es realizar una contextualización y conceptualización de manera preliminar con la finalidad de identificar y caracterizar los productos agrícolas de importancia patrimonial para la provincia de Chimborazo. Como parte del proceso de la Agenda de Competitividad de la Provincia de Chimborazo surgió la necesidad de establecer una investigación que amplié información de base para generar sustentos y criterios que permitan establecer estrategias apropiadas y oportunas, teniendo corresponsabilidad con el esfuerzo de la colectividad chimboracense, especialmente del sector rural, en la apropiación de sus condiciones y la búsqueda de la identidad productiva para la provincia. The Government of Province of Chimborazo had an enriching and participatory process of about three years that resulted in the construction of a Competitiveness Agenda to mark a line of projection for productive development. Within a reading of agricultural strategies, a set of products with a deep social relationship was required, but which present serious weaknesses in terms of productivity and market possibilities, for example, such as diverse varieties of Andean tubers, or certain gramineous, but not for this, we must overreach these crops against development, instead, depending on sustainability they are a priority to rescue, maintain and value. The objective of this work is to make a contextualization and conceptualization in a preliminary way in order to identify and characterize agricultural products of heritage importance for the province of Chimborazo. As part of process from Competitiveness Agenda of Province of Chimborazo, the need arose to establish an investigation that broadened base information to generate support and criteria for establishing appropriate and timely strategies, co-responsibility with the effort of the Chimboracense community, especially the rural sector, in the appropriation of their conditions and the search for productive identity for the province. Palabras clave: Gestión social, Sostenibilidad, Línea de tiempo, Salvaguardia, Sistematización. Keywords: Social management, Sustainability, Timeline, Safeguard, Systematization

Cell death in hepatocellular carcinoma: Pathogenesis and therapeutic opportunities

Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer and the third leading cause of cancer death worldwide. Closely associated with liver inflammation and fibrosis, hepatocyte cell death is a common trigger for acute and chronic liver disease arising from different etiologies, including viral hepatitis, alcohol abuse, and fatty liver. In this review, we discuss the con-tribution of different types of cell death, including apoptosis, necroptosis, pyroptosis, or autophagy, to the progression of liver disease and the development of HCC. Interestingly, inflammasomes have recently emerged as pivotal innate sensors with a highly pathogenic role in various liver diseases. In this regard, an increased inflammatory response would act as a key element promoting a pro-oncogenic microenvironment that may result not only in tumor growth, but also in the formation of a premetastatic niche. Importantly, nonparenchymal hepatic cells, such as liver sinusoidal endothelial cells, hepatic stellate cells, and hepatic macrophages, play an important role in establishing the tumor microenvironment, stimulating tumorigenesis by paracrine communication through cytokines and/or angiocrine factors. Finally, we update the potential therapeutic options to inhibit tumorige-nesis, and we propose different mechanisms to consider in the tumor microenvironment field for HCC resolution. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

Local uterine Ang-(1-7) infusion augments the expression of cannabinoid receptors and differentially alters endocannabinoid metabolizing enzymes in the decidualized uterus of pseudopregnant rats

Background Endocannabinoids (ECs) are important contributors to implantation and decidualization and are suppressed in early pregnancy. Elevated levels of anandamide (AEA), the endogenous ligand for the CB1 and CB2 receptors (R), interfere with receptivity of the blastocyst. Ang-(1–7) is down-regulated in the implantation site (IS) in normal pregnancy at day 7 of gestation. We determined the effects of intra-uterine angiotensin-(1–7) [Ang-(1–7)] (24 microg/kg/h) or vehicle given into the left uterine horn on the ECs in the decidualized uterus. Methods Ovariectomized rats were sensitized for the decidual cell reaction by steroid treatment and decidualization was induced by a bolus of oil injected into the left horn; the right horn served as a control. Results Decidualization increased endometrial permeability (3.1+/−0.2 vs. 7.1+/−0.5 uterus/muscle of cpm of (125)I-BSA, p \u3c 0.0001). VEGF mRNA was increased by the decidualization (1.4-fold, p \u3c 0.05) and by Ang-(1–7) (2.0-fold, p \u3c 0.001). CB1R mRNA was reduced by decidualization (2.7-fold, p \u3c 0.001), but increased by Ang-(1–7) (1.9-fold, p \u3c 0.05). CB2R mRNA was increased by decidualization (4-fold, p \u3c 0.05) and by Ang-(1–7) (2.4-fold, p \u3c 0.001). The enzyme metabolizing AEA, fatty acid amide hydrolase (FAAH), was reduced by decidualization (7.8 fold, p \u3c 0.001) and unchanged by Ang-(1–7) (p \u3e 0.05), whereas the enzyme metabolizing 2-arachidonoylglycerol, monoacyl glycerol lipase (MAGL), was unchanged by decidualization (p \u3e 0.05) and increased by Ang-(1–7) (1.7 fold, p \u3c 0.001). Conclusions These findings report for the first time that Ang-(1–7) augments the expression of CB1R, CB2R and MAGL in the decidualized uterus and thus may interfere with the early events of decidualization

Produtos químicos como desreguladores endócrinos: substâncias danosas e como devem ser testadas

This paper presents an analysis of the opinions of different groups from: scientists, international regulatory bodies, non-governmental organizations and industry; with an interest in the problem of identifying chemical substances with endocrine disrupting activity. There is also discussion of the consequences that exposure to endocrine disruptors may have for human health, considering concrete issues related to: the estimation of risk; the tests that must be used to detect endocrine disruption; the difficulties to establish an association between dose, time of exposure, individual susceptibility, and effect; and the attempts to create a census of endocrine disruptors. Finally, it is proposed that not all hormonal mimics should be included under the single generic denomination of endocrine disruptors.This work was supported by a 96/99 Research Project from the Health Department of the Andalusian Regional Government

Clinical relevance of the transcriptional signature regulated by CDC42 in colorectal cancer.

CDC42 is an oncogenic Rho GTPase overexpressed in colorectal cancer (CRC). Although CDC42 has been shown to regulate gene transcription, the specific molecular mechanisms regulating the oncogenic ability of CDC42 remain unknown. Here, we have characterized the transcriptional networks governed by CDC42 in the CRC SW620 cell line using gene expression analysis. Our results establish that several cancer-related signaling pathways, including cell migration and cell proliferation, are regulated by CDC42. This transcriptional signature was validated in two large cohorts of CRC patients and its clinical relevance was also studied. We demonstrate that three CDC42-regulated genes offered a better prognostic value when combined with CDC42 compared to CDC42 alone. In particular, the concordant overexpression of CDC42 and silencing of the putative tumor suppressor gene CACNA2D2 dramatically improved the prognostic value. The CACNA2D2/CDC42 prognostic classifier was further validated in a third CRC cohort as well as in vitro and in vivo CRC models. Altogether, we show that CDC42 has an active oncogenic role in CRC via the transcriptional regulation of multiple cancer-related pathways and that CDC42-mediated silencing of CACNA2D2 is clinically relevant. Our results further support the use of CDC42 specific inhibitors for the treatment of the most aggressive types of CRC

El dibujo de alumnos de primaria revelando sentimientos y emociones: una cuestión discutida por la inteligencia emocional

Emotions are associated with significant events that determine the individual's reactions to certain situations. They constitute the basis for the intellectual and sociocultural development of the individual, and the drawing reflects them, develops skills and, when used with colors, demonstrates the feelings at the time of the action, and can be applied to children, youth and adults. Its use provides instruments for the integral development of the person, allowing to learn to deal with emotions, life and development processes. Objective was to identify through drawings, feelings and emotions related to the learning process of the primary school student. Methodology was based on bibliographic and field research, where the drawings produced by children in the 2nd and 3rd year of primary school and presenting good oral communication were analyzed. Exclusion criteria: not being a student of the selected schools, presenting mental problems that contaminate the research, and students carrying psychic problems that make oral communication impossible. In this study, the aim has been to improve the psycho-pedagogical processes that involve school learning through the study of designs and emotional intelligence. Result: The analysis of drawings in school-age children is considered important, in order to understand situations experienced by students inside and outside the school, their fears, their anguish and anger, in addition to all kinds of emotions that may interfere with the teaching learning process.  Las emociones están asociadas a acontecimientos significativos que determinan a las reacciones del individuo ante ciertas situaciones. Constituyen la base para el desarrollo intelectual y sociocultural del individuo, y el dibujo las refleja, desarrolla habilidades y, cuando se utiliza con colores demuestra los sentimientos en el momento de la acción, pudiendo aplicarse a niños, jóvenes y adultos. Su uso proporciona instrumentos para el desarrollo integral de la persona, permitiendo aprender a lidiar con las emociones, la vida y los procesos de desarrollo. Objetivo fue identificar a través de dibujos, sentimientos y emociones relacionadas al proceso de aprendizaje del alumno de la enseñanza primaria. Metodología fue basada en investigación bibliográfica y de campo, donde se analizaron los dibujos producidos por niños del 2º y 3º año de la enseñanza primaria y que presentase buena comunicación oral. Criterios de exclusión: no ser alumno de las escuelas seleccionadas, presentar problemas mentales que contaminase la investigación, y alumnos portadores de problemas psíquicos que imposibiliten la comunicación oral. En este estudio se ha aspirado a mejorar los procesos psicopedagógicos que involucran el aprendizaje escolar a través del estudio de los diseños e inteligencia emocional. Resultado: Considerase importante el análisis de los dibujos en niños de edad escolar, con el fin de entender situaciones vividas por los alumnos dentro y fuera de la escuela, sus miedos, sus angustias y rabia, además de todo tipo de emoción que pueda interferir en el proceso de enseñanza aprendizaje. &nbsp

Listening In on the Past: What Can Otolith δ18O Values Really Tell Us about the Environmental History of Fishes?

Oxygen isotope ratios from fish otoliths are used to discriminate marine stocks and reconstruct past climate, assuming that variations in otolith δ18O values closely reflect differences in temperature history of fish when accounting for salinity induced variability in water δ18O. To investigate this, we exploited the environmental and migratory data gathered from a decade using archival tags to study the behaviour of adult plaice (Pleuronectes platessa L.) in the North Sea. Based on the tag-derived monthly distributions of the fish and corresponding temperature and salinity estimates modelled across three consecutive years, we first predicted annual otolith δ18O values for three geographically discrete offshore sub-stocks, using three alternative plausible scenarios for otolith growth. Comparison of predicted vs. measured annual δ18O values demonstrated >96% correct prediction of sub-stock membership, irrespective of the otolith growth scenario. Pronounced inter-stock differences in δ18O values, notably in summer, provide a robust marker for reconstructing broad-scale plaice distribution in the North Sea. However, although largely congruent, measured and predicted annual δ18O values of did not fully match. Small, but consistent, offsets were also observed between individual high-resolution otolith δ18O values measured during tag recording time and corresponding δ18O predictions using concomitant tag-recorded temperatures and location-specific salinity estimates. The nature of the shifts differed among sub-stocks, suggesting specific vital effects linked to variation in physiological response to temperature. Therefore, although otolith δ18O in free-ranging fish largely reflects environmental temperature and salinity, we counsel prudence when interpreting otolith δ18O data for stock discrimination or temperature reconstruction until the mechanisms underpinning otolith δ18O signature acquisition, and associated variation, are clarified

Seismic structure of the northern continental margin of Spain from ESCIN deep seismic profiles

By the end of the Carboniferous, the crust of the continental shelf in northwestern Spain was made up of deeply rooted structures related to the Variscan collision. From Permian to Triassic times the tectonic setting had changed to mainly extensional and the northern Iberian continental margin underwent rifting during Late Jurassic-Early Cretaceous times, along with sea-floor spreading and the opening of the Bay of Biscay until the Late Cretaceous. Subsequently, the northern Iberian margin was active during the north-south convergence of Eurasia and Iberia in the Tertiary. A multichannel seismic experiment, consisting of two profiles, one north-south (ESCIN-4) crossing the platform margin offshore Asturias, and another (ESCIN-3) crossing the platform margin to the northwest of Galicia, was designed to study the structure of the northern Iberian margin. The ESCIN-4 stacked section reveals inverted structures in the upper crust within the Le Danois Basin. North of the steep continental slope, ESCIN-4 shows a thick sedimentary package from 6 to 9.5 s, two-way travel time (TWT). Within this latter package, a 40-km-long, north-tapering wedge of inclined, mainly south-dipping reflections is thought to represent a buried, Alpine-age accretionary prism. In the north western part of the ESCIN-3 (ESCIN-3-1) stacked section, horizontal reflections from 6.5 to 8.5 s correspond to an undisturbed package of sediments lying above oceanic-type basement. In this part of the line, a few kilometres long, strong horizontal reflection at 11.2 s within the basement may represent an oceanic Moho reflection. Also, a band of reflections dips gently towards the southeast, from the base of the gently dipping continental slope. The part of ESCIN-3 line that runs parallel to the NW-Galicia coast (ESCIN-3-2), is characterized by bright, continuous lower crustal reflections from 8 to 10 s. Beneath the lower crustal reflectivity, a band of strong reflections dips gently toward the southwest from 10 to 13.5 s. The part of ESCIN-3 that parallels the northern margin (ESCIN 3-3), shows good reflectivity in all levels. Upper crustal reflections image the sedimentary fill of probable Mesozoic to recent basins. Mid-crustal reflectivity is characterized by dipping reflections until 8 s that are probably related to compressional Variscan features. The lower crustal level shows 'layered' reflections between 8 and 12 s. Dipping reflections are found below the continental Moho.J. Alvarez-Marrón held a post-doc research grant from the Ministry of Education and Science of Spain. The ESCI-N program was sponsored by the Spanish agencies CICYT (project GEO 90-0660) and FICYT, and STRIDE Program of the EU.Peer Reviewe

Combination of KIR2DS4 and FcγRIIa polymorphisms predicts the response to cetuximab in KRAS mutant metastatic colorectal cancer

Cetuximab is a standard-of-care treatment for RAS wild-type metastatic colorectal cancer (mCRC) but not for those harbor a KRAS mutation since MAPK pathway is constitutively activated. Nevertheless, cetuximab also exerts its effect by its immunomodulatory activity despite the presence of RAS mutation. The aim of this study was to determine the impact of polymorphism FcγRIIIa V158F and killer immunoglobulin-like receptor (KIR) genes on the outcome of mCRC patients with KRAS mutations treated with cetuximab. This multicenter Phase II clinical trial included 70 mCRC patients with KRAS mutated. We found KIR2DS4 gene was significantly associated with OS (HR 2.27; 95% CI, 1.08–4.77; P = 0.03). In non-functional receptor homozygotes the median OS was 2.6 months longer than in carriers of one copy of full receptor. Multivariate analysis confirmed KIR2DS4 as a favorable prognostic marker for OS (HR 6.71) in mCRC patients with KRAS mutation treated with cetuximab. These data support the potential therapeutic of cetuximab in KRAS mutated mCRC carrying non-functional receptor KIR2DS4 since these patients significantly prolong their OS even after heavily treatment. KIR2DS4 typing could be used as predictive marker for identifying RAS mutated patients that could benefit from combination approaches of anti-EGFR monoclonal antibodies and other immunotherapies to overcome the resistance mediated by mutation in RAS.This clinical trial was approved and supported by Merck S.L., an affiliate of Merck KGaA, Darmstadt. Germany [research project number 2010-023580-18, date: 05-06-2014

Tumor-suppressor activity of RRIG1 in breast cancer

<p>Abstract</p> <p>Background</p> <p>Retinoid receptor-induced gene-1 (RRIG1) is a novel gene that has been lost in several types of human cancers. The aim of this study was to determine whether RRIG1 plays a role in breast cancer, such as in the suppression of breast cancer cell growth and invasion.</p> <p>Methods</p> <p>Immunohistochemistry was used to detect RRIG1 expression in breast tissue specimens. Gene transfection was used to restore or knock down RRIG1 expression in breast cancer cell lines for analysis of cell viability, colony formation, and migration/invasion potential. Reverse-transcription polymerase chain reaction and western blot assays were used to detect the changes in gene expression. The RhoA activation assay was used to assess RRIG1-induced inhibition of RhoA activity.</p> <p>Results</p> <p>The immunohistochemical data showed that <it>RRIG1 </it>expression was reduced in breast cancer tissues compared with normal and atypical hyperplastic breast tissues. <it>RRIG1 </it>expression was inversely correlated with lymph node metastasis of breast cancer but was not associated with the status of hormone receptors, such as estrogen receptor, progesterone receptor, or HER2. Furthermore, restoration of <it>RRIG1 </it>expression inhibited proliferation, colony formation, migration, and invasion of breast cancer cells. Expression of RRIG1 also reduced phosphorylated Erk1/2 and Akt levels; c-Jun, MMP9, and Akt expressions; and RhoA activity. In contrast, knockdown of RRIG1 expression promoted breast cancer cell proliferation, colony formation, migration, and invasion potential.</p> <p>Conclusion</p> <p>The data from the current study indicated that <it>RRIG1 </it>expression was reduced or lost in breast cancer and that restoration of RRIG1 expression suppressed breast cancer cell growth and invasion capacity. Future studies will determine the underlying molecular mechanisms and define RRIG1 as a tumor-suppressor gene in breast cancer.</p