Oncogenic transformation of mesenchymal stem cells decreases Nrf2 expression favoring in vivo tumor growth and poorer survival

BACKGROUND: The transcription factor Nrf2 is a key regulator of the cellular antioxidant response, and its activation by chemoprotective agents has been proposed as a potential strategy to prevent cancer. However, activating mutations in the Nrf2 pathway have been found to promote tumorigenesis in certain models. Therefore, the role of Nrf2 in cancer remains contentious. METHODS: We employed a well-characterized model of stepwise human mesenchymal stem cell (MSC) transformation and breast cancer cell lines to investigate oxidative stress and the role of Nrf2 during tumorigenesis. The Nrf2 pathway was studied by microarray analyses, qRT-PCR, and western-blotting. To assess the contribution of Nrf2 to transformation, we established tumor xenografts with transformed MSC expressing Nrf2 (n = 6 mice per group). Expression and survival data for Nrf2 in different cancers were obtained from GEO and TCGA databases. All statistical tests were two-sided. RESULTS: We found an accumulation of reactive oxygen species during MSC transformation that correlated with the transcriptional down-regulation of antioxidants and Nrf2-downstream genes. Nrf2 was repressed in transformed MSC and in breast cancer cells via oncogene-induced activation of the RAS/RAF/ERK pathway. Furthermore, restoration of Nrf2 function in transformed cells decreased reactive oxygen species and impaired in vivo tumor growth (P = 0.001) by mechanisms that included sensitization to apoptosis, and a decreased hypoxic/angiogenic response through HIF-1α destabilization and VEGFA repression. Microarray analyses showed down-regulation of Nrf2 in a panel of human tumors and, strikingly, low Nrf2 expression correlated with poorer survival in patients with melanoma (P = 0.0341), kidney (P = 0.0203) and prostate (P = 0.00279) cancers. CONCLUSIONS: Our data indicate that oncogene-induced Nrf2 repression is an adaptive response for certain cancers to acquire a pro-oxidant state that favors cell survival and in vivo tumor growth

Exploring working conditions as determinants of job satisfaction: an empirical test among Catalonia service workers

Job satisfaction is particularly important in the service industry since it involves direct contact with customers and thus has a direct influence on company performance. We analyzed the impact of ten working conditions on job satisfaction by means of structural equation modelling in a representative stratified random sample of 1553 service sector employees in Catalonia (Spain). We found significant effects in social aspects (recognition of a job well done and social support), followed by psychological loads (emotional demands and job insecurity) and by task contents (development & meaning and predictability). These variables explained 50% of the variance in job satisfaction

Regulation of neutrophil senescence by microRNAs

Neutrophils are rapidly recruited to sites of tissue injury or infection, where they protect against invading pathogens. Neutrophil functions are limited by a process of neutrophil senescence, which renders the cells unable to respond to chemoattractants, carry out respiratory burst, or degranulate. In parallel, aged neutrophils also undergo spontaneous apoptosis, which can be delayed by factors such as GMCSF. This is then followed by their subsequent removal by phagocytic cells such as macrophages, thereby preventing unwanted inflammation and tissue damage. Neutrophils translate mRNA to make new proteins that are important in maintaining functional longevity. We therefore hypothesised that neutrophil functions and lifespan might be regulated by microRNAs expressed within human neutrophils. Total RNA from highly purified neutrophils was prepared and subjected to microarray analysis using the Agilent human miRNA microarray V3. We found human neutrophils expressed a selected repertoire of 148 microRNAs and that 6 of these were significantly upregulated after a period of 4 hours in culture, at a time when the contribution of apoptosis is negligible. A list of predicted targets for these 6 microRNAs was generated from http://mirecords.biolead.org and compared to mRNA species downregulated over time, revealing 83 genes targeted by at least 2 out of the 6 regulated microRNAs. Pathway analysis of genes containing binding sites for these microRNAs identified the following pathways: chemokine and cytokine signalling, Ras pathway, and regulation of the actin cytoskeleton. Our data suggest that microRNAs may play a role in the regulation of neutrophil senescence and further suggest that manipulation of microRNAs might represent an area of future therapeutic interest for the treatment of inflammatory disease

The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) family

The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin motifs) enzymes are secreted, multi-domain matrix-associated zinc metalloendopeptidases that have diverse roles in tissue morphogenesis and patho-physiological remodeling, in inflammation and in vascular biology. The human family includes 19 members that can be sub-grouped on the basis of their known substrates, namely the aggrecanases or proteoglycanases (ADAMTS1, 4, 5, 8, 9, 15 and 20), the procollagen N-propeptidases (ADAMTS2, 3 and 14), the cartilage oligomeric matrix protein-cleaving enzymes (ADAMTS7 and 12), the von-Willebrand Factor proteinase (ADAMTS13) and a group of orphan enzymes (ADAMTS6, 10, 16, 17, 18 and 19). Control of the structure and function of the extracellular matrix (ECM) is a central theme of the biology of the ADAMTS, as exemplified by the actions of the procollagen-N-propeptidases in collagen fibril assembly and of the aggrecanases in the cleavage or modification of ECM proteoglycans. Defects in certain family members give rise to inherited genetic disorders, while the aberrant expression or function of others is associated with arthritis, cancer and cardiovascular disease. In particular, ADAMTS4 and 5 have emerged as therapeutic targets in arthritis. Multiple ADAMTSs from different sub-groupings exert either positive or negative effects on tumorigenesis and metastasis, with both metalloproteinase-dependent and -independent actions known to occur. The basic ADAMTS structure comprises a metalloproteinase catalytic domain and a carboxy-terminal ancillary domain, the latter determining substrate specificity and the localization of the protease and its interaction partners; ancillary domains probably also have independent biological functions. Focusing primarily on the aggrecanases and proteoglycanases, this review provides a perspective on the evolution of the ADAMTS family, their links with developmental and disease mechanisms, and key questions for the future

Cytochrome P450/ABC transporter inhibition simultaneously enhances ivermectin pharmacokinetics in the mammal host and pharmacodynamics in Anopheles gambiae

Mass administration of endectocides, drugs that kill blood-feeding arthropods, has been proposed as a complementary strategy to reduce malaria transmission. Ivermectin is one of the leading candidates given its excellent safety profile. Here we provide proof that the effect of ivermectin can be boosted at two different levels by drugs inhibiting the cytochrome or ABC transporter in the mammal host and the target mosquitoes. Using a mini-pig model, we show that drug-mediated cytochrome P450/ABC transporter inhibition results in a 3-fold increase in the time ivermectin remains above mosquito-killing concentrations. In contrast, P450/ABC transporter induction with rifampicin markedly impaired ivermectin absorption. The same ketoconazole-mediated cytochrome/ABC transporter inhibition also occurs outside the mammal host and enhances the mortality of Anopheles gambiae. This was proven by using the samples from the mini-pig experiments to conduct an ex-vivo synergistic bioassay by membrane-feeding Anopheles mosquitoes. Inhibiting the same cytochrome/xenobiotic pump complex in two different organisms to simultaneously boost the pharmacokinetic and pharmacodynamic activity of a drug is a novel concept that could be applied to other systems. Although the lack of a dose-response effect in the synergistic bioassay warrants further exploration, our study may have broad implications for the control of parasitic and vector-borne diseases

Fractionation of eucalyptus globulus wood by glycerol-water pretreatment: optimization and modeling

A glycerol-organosolv process can be a good alternative for Eucalyptus wood fractionation into its main compounds, improving the enzymatic saccharification of the cellulose. A study of process variables - glycerol−water percent content, temperature, and process time - was carried out using a Box-Behnken experimental design. The cellulose obtained from pretreated solids was recovered almost quantitatively, leading to a solid with a high percentage of cellulose (77 g/100 g of pretreated solid), low lignin content (9 g/100 g of pretreated solid), and 18% of residual hemicellulose in the solid at 200 °C, 56% of glycerol−water and 69 min. The enzymatic saccharification was enhanced achieving 98% cellulose-to-glucose conversion (under conditions: liquid to solid ratio 20 g/g and enzyme loading 20 FPU/g of solid). This study contributes to the improvement of biomass fractionation by exploring an eco-friendly treatment which allows for almost complete wood fractionation into constituents and high levels of glucose recovery available for subsequent yeast fermentation to bioethanol.The authors A. Romani and F. B. Pereira thank to the Portuguese Foundation for Science and Technology (FCT, Portugal) for their fellowships (grant number: SFRH/BPD/77995/2011 and SFRH/BD/64776/2009, respectively)

Incorporating pleiotropic quantitative trait loci in dissection of complex traits: seed yield in rapeseed as an example

© The Author(s) 2017 This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 International License http://creativecommons.org/licenses/by/4.0/), which permits use, duplication, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.Most agronomic traits of interest for crop improvement (including seed yield) are highly complex quantitative traits controlled by numerous genetic loci, which brings challenges for comprehensively capturing associated markers/ genes. We propose that multiple trait interactions underlie complex traits such as seed yield, and that considering these component traits and their interactions can dissect individual quantitative trait loci (QTL) effects more effectively and improve yield predictions. Using a segregating rapeseed (Brassica napus) population, we analyzed a large set of trait data generated in 19 independent experiments to investigate correlations between seed yield and other complex traits, and further identified QTL in this population with a SNP-based genetic bin map. A total of 1904 consensus QTL accounting for 22 traits, including 80 QTL directly affecting seed yield, were anchored to the B. napus reference sequence. Through trait association analysis and QTL meta-analysis, we identified a total of 525 indivisible QTL that either directly or indirectly contributed to seed yield, of which 295 QTL were detected across multiple environments. A majority (81.5%) of the 525 QTL were pleiotropic. By considering associations between traits, we identified 25 yield-related QTL previously ignored due to contrasting genetic effects, as well as 31 QTL with minor complementary effects. Implementation of the 525 QTL in genomic prediction models improved seed yield prediction accuracy. Dissecting the genetic and phenotypic interrelationships underlying complex quantitative traits using this method will provide valuable insights for genomics-based crop improvement.Peer reviewedFinal Published versio

Spatial and temporal analysis of surface temperature in the Apacheta micro-basin using Landsat thermal data

[EN] High Andean ecosystems, such as grasslands and peatlands, are fragile and, due to the effects of climate change, their sustainability is being jeopardized. A key factor hampering sustainable management efforts from the government and communities, is the lack or scarcity of in-situ eco-hydrological and climate data. In that sense, remote sensing techniques offers a powerful alternative for the assessment of the evolution of these ecosystems, by providing a holistic view of the territory. The objective of this work is to determine both the spatial and temporal evolution of the local atmospheric temperature of the Apacheta micro-basin in Ayacucho over the past 34 years, using the soil surface temperature (SST) as a proxy. For this, thermal data of Landsat series (TM, ETM+ and TIRS sensors), covering the period from 1985 to 2018, were used. The TSS estimates were made from the emissivity correction of the brightness temperatures at the top of the atmosphere, considering the negligible atmospheric effect due to the conditions of high atmospheric transmissivity in the study area. The results show a positive trend of the SST with an increase of 4.9 °C, equivalent to 27.5% of the SST. Trends are higher (5.8 °C) in the snowy areas (equivalent to 35.3% of the TSS in the whole micro-basin). The SST in the snow area explains the 83.6% of the behavior of the snow cover derived by the NDSI, with a decreasing surface as SST increase.[ES] Los ecosistemas altoandinos, como los pastizales y las turberas, son frágiles y, debido a los efectos del cambio climático, su sostenibilidad está en peligro. Un factor clave que obstaculiza los esfuerzos de gestión sostenible del gobierno y las comunidades es la falta o escasez de datos eco-hidrológicos y climáticos in situ. En ese sentido, las técnicas de teledetección ofrecen una poderosa alternativa para la evaluación de la evolución de esos ecosistemas, al proporcionar una visión holística del territorio. El objetivo de este trabajo es determinar la evolución espacial y temporal de la temperatura atmosférica local de la microcuenca Apacheta en Ayacucho en los últimos 34 años, utilizando la temperatura superficial del suelo (TSS) como aproximación. Para ello, se utilizaron los datos térmicos de la serie Landsat (sensores TM, ETM+ y TIRS), que abarcan el período comprendido entre 1985 y 2018. Las estimaciones de TSS se realizaron a partir de la corrección de emisividad de las temperaturas de brillo a nivel del techo de la atmósfera, considerando el efecto atmosférico despreciable debido a las condiciones de alta transmisividad atmosférica de la zona de estudio. Los resultados muestran una tendencia positiva de la TSS con un aumento de 4,9 °C, equivalente al 27,5% de la TSS. Las tendencias son más altas (5,8 °C) en las zonas nevadas (equivalente al 35,3% de la TSS en toda la microcuenca). La TSS en la zona de nieve explica el 83,6% del comportamiento de la cubierta de nieve derivado del NDSI, con una superficie decreciente a medida que la TSS aumenta.Este trabajo ha sido posible gracias al apoyo financiero de los proyectos “Strengthening resilience of Andean river basin headwaters facing global change” (PGA_084063) y “Agua-Andes: Ecological infrastructure strategies for enhancing water sustainability in the semi-arid Andes” financiados por el Programa PEER de USAID, y el proyecto “International Water Security Network”, financiado por el Lloyd’s Register Foundation. Los autores agradecen a la Universidad Nacional de San Cristóbal de Huamanga por su incondicional apoyo.Moncada, W.; Willems, B. (2020). Análisis espacial y temporal de la temperatura superficial en la microcuenca Apacheta mediante datos térmicos Landsat. Revista de Teledetección. 0(57):51-63. https://doi.org/10.4995/raet.2020.13855OJS5163057Aguilar, H., Mora, R., Vargas, C. 2014. Metodología para la corrección atmosférica de imágenes Aster, Rapideye, Spot 2 y Landsat 8 con el módulo Flaash del software Envi. Revista Geográfica de América Central, 2(53), 39-59. https://doi.org/10.15359/rgac.2-53.2Aguilar, J., Espinoza, R., Espinoza, J.C., Rojas, J., Willems, B.L., Leyva, W.M. 2019. Elevationdependent warming of land surface temperatures in the Andes assessed using MODIS LST time series (2000-2017). International Journal of Applied Earth Observation and Geoinformation, 77, 119- 128. https://doi.org/10.1016/j.jag.2018.12.013Araghi, A., Mousavi-Baygi, M., Adamowski, J. 2017. Detecting soil temperature trends in Northeast Iran from 1993 to 2016. Soil and Tillage Research, 174, 177-192. https://doi.org/10.1016/j.still.2017.07.010Artis, D. A., Carnahan, W.H. 1982. Survey of emissivity variability in thermography of urban areas. Remote Sensing of Environment, 12(4), 313-329. https://doi.org/10.1016/0034-4257(82)90043-8Arvidson, T., Barsi, J., Jhabvala, M., Reuter, D. 2013. Landsat and Thermal Infrared Imaging. En C. Kuenzer & S. Dech (Eds.), Thermal Infrared Remote Sensing: Sensors, Methods, Applications (pp. 177-196). Springer Netherlands. https://doi.org/10.1007/978-94-007-6639-6_9Avdan, U., Jovanovska, G. 2016. Algorithm for Automated Mapping of Land Surface Temperature Using Landsat 8 Satellite Data. Journal of Sensors, 2016, 1480307-1480307. https://doi.org/10.1155/2016/1480307Carlson, T.N., Ripley, D.A. 1997. On the relation between NDVI, fractional vegetation cover, and leaf area index. Remote Sensing of Environment, 62(3), 241-252. https://doi.org/10.1016/S0034-4257(97)00104-1Caselles, E., Abad, F.J., Valor, E., Caselles, V. 2011. Automatic Generation of Land Surface Emissivity Maps. Climate Change - Research and Technology for Adaptation and Mitigation, 15. https://doi.org/10.5772/24968Chi, Y., Sun, J., Sun, Y., Liu, S., Fu, Z. 2020. Multitemporal characterization of land surface temperature and its relationships with normalized difference vegetation index and soil moisture content in the Yellow River Delta, China. Global Ecology and Conservation, 23, e01092. https://doi.org/10.1016/j.gecco.2020.e01092Dozier, J. 1989. Spectral signature of alpine snow cover from the Landsat thematic mapper. Remote Sensing of Environment, 28, 9-22. https://doi.org/10.1016/0034-4257(89)90101-6Gutman, G., Ignatov, A. 1998. The derivation of the green vegetation fraction from NOAA/AVHRR data for use in numerical weather prediction models. International Journal of Remote Sensing, 19(8), 1533- 1543. https://doi.org/10.1080/014311698215333Huete, A., Didan, K., Miura, T., Rodriguez, E.P., Gao, X., Ferreira, L.G. 2002. Overview of the radiometric and biophysical performance of the MODIS vegetation indices. Remote Sensing of Environment, 83(1), 195-213. https://doi.org/10.1016/S0034-4257(02)00096-2ITT Visual Information Solutions. 2009. ENVI Atmospheric Correction Module: QUAC and FLAASH User's Guide, Version 4.7, pp. 44. http://www.harrisgeospatial.com/portals/0/pdfs/ envi/Flaash_Module.pdfJiménez-Muñoz, J.C., Sobrino, J.A., Skoković, D., Mattar, C., Cristóbal, J. 2014. Land Surface Temperature Retrieval Methods From Landsat-8 Thermal Infrared Sensor Data. IEEE Geoscience and Remote Sensing Letters, 11(10), 1840-1843. https://doi.org/10.1109/LGRS.2014.2312032Mendoza, J.N. 2014. Implementación de un método operativo para la estimación de la temperatura superficial terrestre en la Región Callao usando datos de las imágenes satelitales. Universidad Nacional del Callao, 53. http://repositorio.unac.edu.pe/handle/UNAC/966Moncada, W., Pereda, A., Aldana, C., Masias, M., Jiménez, J. 2015. Cuantificación hidrográfica de la cuenca del río Cachi-Ayacucho, mediante imágenes satelitales. Instituto de Investigación Científica e innovación Tecnológica de la UNSCH, II.Moncada, W., Willems, B., Rojas, J. 2020. Estimación de estadíos estacionales a partir de parámetros climáticos medidos en la estación meteorológica de la microcuenca Apacheta, Región Ayacucho, 2000 al 2018. Revista de Investigación de Física. UNMSM, 23(2), 17-25. https://fisica.unmsm.edu.pe/ rif/previo_files/2020-2/03moncada.pdfPereda, A., Moncada, W., Verde, L. 2018. Respuesta nival de la cabecera de cuenca Cachi-Apacheta de Ayacucho: Vol. I. Editorial Académica Española. https://www.morebooks.shop/store/es/book/ respuesta-nival-de-la-cabecera-de-cuenca-cachiapacheta-de-ayacucho/isbn/978-620-2-12620-5Quispe, B.J., Révolo, R.H. 2020. Temperatura superficial y estado de la vegetación del bosque de Polylepis spp, distrito de San Marcos de Rocchac, Huancavelica - Perú. Enfoque UTE, 11(3), 69-86. https://doi.org/10.29019/enfoque.v11n3.592Rudjord, Due, 2012. Evaluation of FLAASH atmospheric correction (SAMBA/10/12; p. 24). Norwegian Computing Center. http://publications. nr.no/1338298623/Rudjord-Trier_FLAASH_2012. pdfSantos, B. 2016. Cubierta Nival y Temperaturas de Superficie en Sierra Nevada a través del tratamiento digital de imágenes de satélite [Tesis Doctoral, Universitat de Barcelona]. http://diposit.ub.edu/dspace/handle/2445/108441Sayão, V.M., Demattê, J.A.M., Bedin, L.G., Nanni, M.R., Rizzo, R. 2018. Satellite land surface temperature and reflectance related with soil attributes. Geoderma, 325, 125-140. https://doi.org/10.1016/j.geoderma.2018.03.026Sobrino, J., Jiménez, J., Paolini, L. 2004. Land surface temperature retrieval from Landsat TM 5. Remote Sensing of Environment, 90(4), 434-440. https://doi.org/10.1016/j.rse.2004.02.003Solman, S.A., Nuñez, M.N., Cabré, M.F. 2008. Regional climate change experiments over southern South America. I: Present climate. Climate Dynamics, 30(5), 533-552. https://doi.org/10.1007/s00382-007-0304-3USGS, Landsat Collections, Landsat Missions. Consultado el 14 de octubre de 2019, de https://www.usgs.gov/land-resources/nli/landsat.Vuille, M., Bradley, R.S. 2000. Mean annual temperature trends and their vertical structure in the tropical Andes. Geophysical Research Letters, 27(23), 3885- 3888. https://doi.org/10.1029/2000GL011871Weng, Q., Lu, D., Schubring, J. 2004. Estimation of land surface temperature-vegetation abundance relationship for urban heat island studies. Remote Sensing of Environment, 89(4), 467-483. https://doi.org/10.1016/j.rse.2003.11.005Xu, C., Qu, J.J., Hao, X., Zhu, Z., Gutenberg, L. 2020. Surface soil temperature seasonal variation estimation in a forested area using combined satellite observations and in-situ measurements. 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Identifying chondroprotective diet-derived bioactives and investigating their synergism

Osteoarthritis (OA) is a multifactorial disease and nutrition is a modifiable factor that may contribute to disease onset or progression. A detailed understanding of mechanisms through which diet-derived bioactive molecules function and interact in OA is needed. We profiled 96 diet-derived, mainly plant-based bioactives using an in vitro model in chondrocytes, selecting four candidates for further study. We aimed to determine synergistic interactions between bioactives that affected the expression of key genes in OA. Selected bioactives, sulforaphane, apigenin, isoliquiritigenin and luteolin, inhibited one or more interleukin-1-induced metalloproteinases implicated in OA (MMP1, MMP13, ADAMTS4, ADAMTS5). Isoliquiritigenin and luteolin showed reactive oxygen species scavenging activity in chondrocytes whereas sulforaphane had no effect and apigenin showed only a weak trend. Sulforaphane inhibited the IL-1/NFκB and Wnt3a/TCF/Lef pathways and increased TGFβ/Smad2/3 and BMP6/Smad1/5/8 signalling. Apigenin showed potent inhibition of the IL-1/NFκB and TGFβ/Smad2/3 pathways, whereas luteolin showed only weak inhibition of the IL-1/NFκB pathway. All four bioactives inhibited cytokine-induced aggrecan loss from cartilage tissue explants. The combination of sulforaphane and isoliquiritigenin was synergistic for inhibiting MMP13 gene expression in chondrocytes. We conclude that dietary-derived bioactives may be important modulators of cartilage homeostasis and synergistic relationships between bioactives may have an anti-inflammatory and chondroprotective role

Evaluación del valor nutritivo de la variedad de maíz ICA V557 adaptada a clima frío, en cerdos en crecimiento y acabado.

Se pretende mostrar el alto valor nutritivo de la variedad de maíz ICA V 557 comparado con el maíz común, en la alimentación de cerdos en crecimiento y acabado. El experimetno se realiza en la Sabana de Bogotá, Colombia, a 2.640 m.s.n.m. Se emplean 18 cerdos con peso promedio inicial de 18.8 kg, los que se asignan a tres tratamientos en un diseño completamente al azar, sobre la base de peso, sexo y raza. Cada tratamiento tuvo 2 repeticiones. En el tratamiento 1 se suministra maíz normal y torta de soya, el tratamiento 2 es a base de maíz opaco, el tratamiento 3 es a base de maíz normal. Los animales reciben dieta de crecimiento hasta los 50 a 55 kg, momento en que se cambia a dieta de acabado. El tratamiento con maíz opaco hace superior en 30 por ciento el aumento de peso diario en comparación con los resultados con maíz normal. La eficiencia de conversión alimenticia es mejor significativamente para los cerdos bajo el régimen de maíz normal más torta de soya y de maíz opaco. Estos resultados se obtienen en la fase de crecimiento. En la fase de acabado se obtienen los siguientes resultados. Los cerdos sometidos al tratamiento con maíz opaco crecieron tan rápida y eficientemente como los que consumieron maíz y soya. Los cerdos alimentados con maíz normal tuvieron ganancias de peso más lentas y menos eficientes. Los cerdos bajo el régimen de maíz opaco presentaron el mayor espesor de la grasa dorsal, así como los mayores rendimientos en canal y área de la sección transversal del músculo longissimusdorsiMaíz-zea maysPorcicultur