Subversion of Ras Small GTPases in Cutaneous Melanoma Aggressiveness

The rising incidence and mortality rate associated with the metastatic ability of cutaneous melanoma represent a major public health concern. Cutaneous melanoma is one of the most invasive human cancers, but the molecular mechanisms are poorly understood. Moreover, currently available therapies are not efficient in avoiding melanoma lethality. In this context, new biomarkers of prognosis, metastasis, and response to therapy are necessary to better predict the disease outcome. Additionally, the knowledge about the molecular alterations and dysregulated pathways involved in melanoma metastasis may provide new therapeutic targets. Members of the Ras superfamily of small GTPases regulate various essential cellular activities, from signaling to membrane traffic and cytoskeleton dynamics. Therefore, it is not surprising that they are differentially expressed, and their functions subverted in several types of cancer, including melanoma. Indeed, Ras small GTPases were found to regulate melanoma progression and invasion. Hence, a better understanding of the mechanisms regulated by Ras small GTPases that are involved in melanoma tumorigenesis and progression may provide new therapeutic strategies to block these processes. Here, we review the current knowledge on the role of Ras small GTPases in melanoma aggressiveness and the molecular mechanisms involved. Furthermore, we summarize the known involvement of these proteins in melanoma metastasis and how these players influence the response to therapy.publishersversionpublishe

Unraveling the relevance of arl gtpases in cutaneous melanoma prognosis through integrated bioinformatics analysis

Funding Information: Funding: This research was funded by iNOVA4Health—UIDB/04462/2020, a program financially supported by the Fundação para a Ciência e Tecnologia/Ministério da Educação e Ciência. M.P. was funded by the Liga Portuguesa Contra o Cancro ‒ Núcleo Regional do Sul (LPCC‐NRS). D.B. was funded by the FCT Investigator Program (IF/00501/2014/CP1252/CT0001). Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.Cutaneous melanoma (CM) is the deadliest skin cancer, whose molecular pathways underlying its malignancy remain unclear. Therefore, new information to guide evidence‐based clinical decisions is required. Adenosine diphosphate (ADP)‐ribosylation factor‐like (ARL) proteins are membrane trafficking regulators whose biological relevance in CM is undetermined. Here, we investigated ARL expression and its impact on CM prognosis and immune microenvironment through integrated bioinformatics analysis. Our study found that all 22 ARLs are differentially expressed in CM. Specifically, ARL1 and ARL11 are upregulated and ARL15 is downregulated regardless of mutational frequency or copy number variations. According to TCGA data, ARL1 and ARL15 represent independent prognostic factors in CM as well as ARL11 based on GEPIA and OncoLnc. To investigate the mechanisms by which ARL1 and ARL11 increase patient survival while ARL15 reduces it, we evaluated their correlation with the immune microenvironment. CD4+ T cells and neutrophil infiltrates are significantly increased by ARL1 expression. Furthermore, ARL11 expression was correlated with 17 out of 21 immune infiltrates, including CD8+ T cells and M2 macrophages, described as having anti‐tumoral activity. Likewise, ARL11 is interconnected with ZAP70, ADAM17, and P2RX7, which are implicated in immune cell activation. Collectively, this study provides the first evidence that ARL1, ARL11, and ARL15 may influence CM progression, prognosis, and immune microenvironment remodeling.publishersversionpublishe

Fruit set and development of tomato grown in greenhouse : application of variable doses of plant growth regulators.

Las hormonas vegetales son capaces de controlar el desarrollo reproductivo, desde la diferenciación floral hasta los últimos estadios del desarrollo de los frutos. En particular, la etapa de fructificación y desarrollo depende del contenido endógeno de estas sustancias, y es posible manipular la iniciación del desarrollo del fruto por aplicación externa de hormonas. Previamente se evaluó el proceso de fructificación y desarrollo en el cultivo de tomate en invernadero en respuesta a la aplicación de b-NOA y AG3 en dosis fijas: se observó sensibilidad diferencial dependiendo del genotipo y tipo de regulador. El objetivo de este trabajo fue establecer dosis y momento óptimo para la aplicación de b-NOA y AG3 como formas de mejorar la fructificación y el desarrollo de frutos partenocárpicos. Como factores se consideraron tipo de regulador -b-NOA y AG3- en dosis y momentos de aplicación variables. Empleando ovarios no polinizados como sistema experimental fue posible concluir que la aplicación de 40 ppm de b-NOA a 7 días post antesis ofrece las mayores ventajas desde el punto de vista del rendimiento y menor impacto fisiológico, sin alterar el período de desarrollo de los frutos.Vegetable hormones are capable of controlling the reproductive development, from the flower differentiation until the last stages in the fruit development. In particular, the fruit set and development stage depends on the endogenous content of this substance, being possible to manipulate the beginning of the fruit development by external application of hormones. We have previously evaluated the fruit set and development process in tomato cultivation in greenhouse in response to the application of b-NOA and GA3 in fixed doses. Differential sensitivity was observed depending on the genotype and regulator type. The purpose of this work is to establish the optimum dose and moment for the application of b-NOA and GA3 as ways to improve the fruit set and development of parthenocarpic fruits. Regulator types b-NOA and GA3 in variable doses and application moments were considered as factors. Using unpollinated ovaries as an experimental system, it was possible to conclude that the application of 40 ppm of b-NOA at 7 days post antesis would offer the best advantages from a performance point of view and a lower physiologic impact, not altering the period of fruit development.Fil: Agüero, Marta S..Fil: Barral, Gabriela.Fil: Miguelisse, Nancy E..Fil: Castillo, Oscar E.

Long-term avian influenza virus epidemiology in a small Spanish wetland ecosystem is driven by the breeding Anseriformes community

During 2007–2009 and 2012–2014, avian influenza virus (AIV) was studied in a wild avian community of a northern Spanish wetland using non-invasive sampling methods and host identification by COI barcoding. The aim of this longitudinal study was to evaluate AIV dynamics in a natural wetland ecosystem, taking into account both virological aspects and ecological traits of hosts. Global AIV prevalence decreased significantly during the second sampling period (0.3%) compared to the first (6.6%). Circulating subtype distributions were also different between periods, with a noteworthy H5 and H7 subtype richness during the first sampling period. Mallard Anas platyrhynchos was identified as the main AIV host, although not all positive samples could be ascribed to the host. We modelled AIV prevalence with regard to the avian host community composition and meteorological data from the wetland. Statistical analysis revealed seasonal differences in AIV detection, with higher prevalence during the breeding season compared to other phenological events. The model also shows that the lower AIV prevalence during the second study period was associated with a significant reduction of breeding Anseriformes in the wetland, revealing a long-term fluctuation of AIV prevalence driven by the breeding Anseriformes community. This longitudinal study on AIV epidemiology in a natural ecosystem reveals that although prevalence follows seasonal and annual patterns, long-term prevalence fluctuation is linked to the breeding community composition and size. These results are relevant to understanding the influence of host ecology on pathogen transmission for preventing and managing influenza emergence.This study has been funded by the Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA) (RTA2011-00111-C03 Grant) and Departamento de Desarrollo Económico e Infraestructuras del Gobierno Vasco. OT was recipient of an INIA predoctoral grant. PA is supported by Ministerio de Economia, industria y competitividad del Gobierno de España and Universidad de Castilla-La Mancha through “Ramón y Cajal” contract (RYC-2012-11970).Peer reviewe

Fruit set and development of tomato grown in greenhouse : effect of plant growth regulators

El proceso de fructificación y desarrollo en tomate puede ser inducido naturalmente por polinización o partenocarpia y artificialmente por aplicación de reguladores; esta respuesta es variable según tipo y dosis de hormona, momento de aplicación y cultivar involucrado. El objetivo de este trabajo fue evaluar la capacidad de auxinas y giberelinas para inducir el desarrollo partenocárpico en genotipos de crecimiento indeterminado. Como factores se consideraron tipo de regulador -AG3 y β-NOA- en dosis fija, momento de aplicación -0, 5, 12, 19, 26 dpa- y genotipo -Rutgers, Fortaleza F1 y Colt 45-. Las mejores respuestas a nivel de porcentaje de fructificación y peso fresco se obtuvieron con β-NOA en comparación con AG3. Considerando todos los factores analizados, solamente la aplicación de β-NOA a 5 dpa permitió alcanzar porcentajes de fructificación y tamaño final de frutos similares a los obtenidos por autopolinización. El período de sensibilidad y el tamaño final de los frutos presentaron interacción con las variables genotipo, momento de aplicación y tipo de regulador. Se observó además que AG3 provocó un escaso desarrollo placentario y ausencia de óvulos mientras que β-NOA indujo un desarrollo de placentas y óvulos similar al de los frutos obtenidos por autopolinización.The process of fruit set and development in tomato can be naturally induced by pollination or parthenocarpy and artificiall y by hormonal application; this response is variable according to type and dose of the hormone, moment of application and cultivar involved. The purpose of this work was to evaluate the capacity of auxins and gibberellins to induce the parthenocarpic development in genotypes of undetermined growth. The considered factors were type of regulator -AG3 and β-NOAin set dose, moment of application -0, 5, 12, 19, 26 dpa-, and genotype -Rutgers, Fortaleza F1 and Colt 45-. The best responses regarding percentage of fructification and fresh weight are obtained with β-NOA in comparison with AG3. Considering all the analyzed factors, only the application of β-NOA to 5 dpa allowed to obtain the percentages of fruit set and final size of fruits similar to the ones obtained by autopollination. The period of sensitivity and the final size of fruits presented interaction with the genotype variables, moment of application and type of regulator. It was also observed that AG3 caused a scarce placental development and ovule absence while β-NOA induced a placenta and ovule development similar to the one in fruits obtained by autopollination.Fil: Castillo, Oscar E..Fil: Barral, Gabriela.Fil: Rodríguez, Gustavo.Fil: Miguelisse, Nancy E..Fil: Agüero, Marta S.

Bottle aging and storage of wines: a review

Wine is perhaps the most ancient and popular alcoholic beverage worldwide. Winemaking practices involve careful vineyard management alongside controlled alcoholic fermentation and potential aging of the wine in barrels. Afterwards, the wine is placed in bottles and stored or distributed in retail. Yet, it is considered that wine achieves its optimum properties after a certain storage time in the bottle. The main outcome of bottle storage is a decrease of astringency and bitterness, improvement of aroma and a lighter and more stable color. This is due to a series of complex chemical changes of its components revolving around the minimized and controlled passage of oxygen into the bottle. For this matter, antioxidants like sulfur oxide are added to avoid excessive oxidation and consequent degradation of the wine. In the same sense, bottles must be closed with appropriate stoppers and stored in adequate, stable conditions, as the wine may develop unappealing color, aromas and flavors otherwise. In this review, features of bottle aging, relevance of stoppers, involved chemical reactions and storage conditions affecting wine quality will be addressed.The research leading to these results was funded by FEDER under the program Interreg V-A Spain-Portugal (POPTEC) 2014-2020 ref. 0377_IBERPHENOL_6_E and ref. 0181_NANOEATERS_ 01_E; to Xunta de Galicia supporting with the Axudas Conecta Peme the IN852A 2018/58 NeuroFood Project and the program EXCELENCIA-ED431F 2020/12; to Ibero-American Program on Science and Technology (CYTED—AQUA-CIBUS, P317RT0003) and by the Bio Based Industries Joint Undertaking (JU) under grant agreement No 888003 UP4HEALTH Project (H2020-BBIJTI-2019), the JU receives support from the European Union’s Horizon 2020 research and innovation program and the Bio Based Industries Consortium. The research leading to these results was supported by MICINN supporting the Ramón & Cajal grant for M.A. Prieto (RYC-2017-22891); by Xunta de Galicia and University of Vigo supporting the post-doctoral grant of M. Fraga-Corral (ED481B-2019/096).info:eu-repo/semantics/publishedVersio

Development and validation of an enzyme-linked immunosorbent assay for antibodies against Mycobacterium bovis in european wild boar

<p>Abstract</p> <p>Background</p> <p>Bovine tuberculosis (bTB) remains a significant problem in some parts of Spain largely because of contacts between cattle and wildlife reservoirs in extensive grazing systems. European Wild boar (<it>Sus scrofa</it>) is one of the species involved in the transmission of the disease to other species. Fast and simple detection methods would be critical for assessing infection prevalence, study the mechanisms of pathogen transmission and monitoring the effects of TB control measures.</p> <p>Results</p> <p>An enzyme-linked immunosorbent assay (ELISA) to detect antibodies against <it>Mycobacterium bovis </it>in wild boar serum was developed and validated on 185 sera from TB positive and negative wild boar. Based on antigen inoculation of captive animals as well as tuberculosis compatible lesions, culture results and molecular analysis of hunted individuals, animals were allocated into two groups: tuberculosis positive group and tuberculosis negative group. After optimization of the positive to negative ratio using different combinations of serum dilutions and conjugate concentrations, the test yielded a sensitivity of 72.60% and a specificity of 96.43% for the best cut-off.</p> <p>Conclusion</p> <p>Although some negative group animals showed an ELISA positive reaction (< 3%), this assay showed a high potential for accurate diagnosis of TB in wild boar, as its large dynamic range supported a good discriminatory power and a satisfactory balance between sensitivity and specificity.</p

Ditopic receptors containing urea groups for solvent extraction of Cu(II) salts

[Abstract] The ditopic receptor L3 [1-(2-((7-(4-(tert-butyl)benzyl)-1,4,7,10-tetraazacyclododecan-1-yl)methyl)phenyl)-3-(3-nitrophenyl)urea] containing a macrocyclic cyclen unit for Cu(II)-coordination and a urea moiety for anion binding was designed for recognition of metal salts. The X-ray structure of [CuL3(SO4)] shows that the sulfate anion is involved in cooperative binding via coordination to the metal ion and hydrogen-bonding to the urea unit. This behaviour is similar to that observed for the related receptor L1 [1-(2-((bis(pyridin-2-ylmethyl)amino)methyl)phenyl)-3-(3-nitrophenyl)urea], which forms a dimeric [CuL1(μ-SO4)]2 structure in the solid state. In contrast, the single crystal X-ray structure of [ZnL3(NO3)2] contains a 1 : 2 complex (metal : anion) where one anion coordinates to the metal and the other is hydrogen-bonded to the urea group. Spectrophotometric titrations performed for the [CuL3(OSMe2)]2+ complex indicate that this system is able to bind a wide range of anions with an affinity sequence: MeCO2− > Cl− > H2PO4− > Br− > NO2− > HSO4− > NO3−. Lipophilic analogues of L1 and L3 extract CuSO4 and CuCl2 from water into chloroform with high selectivity over the corresponding Co(II), Ni(II) and Zn(II) salts.Xunta de Galicia; EM 2012/088Xunta de Galicia; CN-2012/01

Análisis de los factores que otorgan credibilidad al presentador de informativos en televisión

La credibilidad es un concepto clave para asentar la eficacia comunicativa de un informativo en televisión. Sobre el presentador recae en muchas ocasiones la responsabilidad de que la información emitida llegue a los espectadores de la manera más creíble y profesional posible. El presentador se convierte entonces en el último y fundamental eslabón de la cadena de producción, el responsable de establecer un “gancho” con la audiencia que dará lugar a una relación diaria y fiel. En el presente trabajo nos proponemos analizar los factores que contribuyen a la credibilidad del presentador desde un punto de vista teórico a través de la revisión de la literatura existente y también práctico, mediante un análisis cualitativo que toma como referencia las opiniones de destacados presentadores de informativos españoles, en televisiones públicas y privadas, de ámbito nacional y también autonómico