Presentación del dossier: Los tiempos de las paces populares. Pluralidades de(s)coloniales contra la hegemonía (neo)liberal

Presentation of the dossier: The times of popular peace. De(s)colonial pluralities against neoliberal hegemony  Presentación del dossier: Los tiempos de las paces populares. Pluralidades de(s)coloniales contra la hegemonía (neo)liberalPresentación del dossier: Los tiempos de las paces populares. Pluralidades de(s)coloniales contra la hegemonía (neo)libera

Metastatic risk and resistance to BRAF inhibitors in melanoma defined by selective allelic loss of ATG5

Melanoma is a paradigm of aggressive tumors with a complex and heterogeneous genetic background. Still, melanoma cells frequently retain developmental traits that trace back to lineage specification programs. In particular, lysosome-associated vesicular trafficking is emerging as a melanoma-enriched lineage dependency. However, the contribution of other lysosomal functions such as autophagy to melanoma progression is unclear, particularly in the context of metastasis and resistance to targeted therapy. Here we mined a broad spectrum of cancers for a meta-analysis of mRNA expression, copy number variation and prognostic value of 13 core autophagy genes. This strategy identified heterozygous loss of ATG5 at chromosome band 6q21 as a distinctive feature of advanced melanomas. Importantly, partial ATG5 loss predicted poor overall patient survival in a manner not shared by other autophagy factors and not recapitulated in other tumor types. This prognostic relevance of ATG5 copy number was not evident for other 6q21 neighboring genes. Melanocyte-specific mouse models confirmed that heterozygous (but not homozygous) deletion of Atg5 enhanced melanoma metastasis and compromised the response to targeted therapy (exemplified by dabrafenib, a BRAF inhibitor in clinical use). Collectively, our results support ATG5 as a therapeutically relevant dose-dependent rheostat of melanoma progression. Moreover, these data have important translational implications in drug design, as partial blockade of autophagy genes may worsen (instead of counteracting) the malignant behavior of metastatic melanomas.M.S.S. is funded by grants from the Spanish Ministry of Economy and Innovation (projects SAF2011-28317, SAF2014-56868-R and RTC-2014-2442-1), as well as a Team Science Award by the Melanoma Research Alliance, and grants from the Worldwide Cancer Research and the Asociacion Espanola Contra el Cancer (AECC). M.G-F was funded by a Juan de la ~ Cierva postdoctoral fellowship from the Spanish Ministry of Education and P.K and M.C. by predoctoral fellowships from Fundación La Caixa

El Sistema de El Hayéu del Osu, Mazizo Occidental de los Picos de Europa

Los Picos de Europa representan la mayor concentración de cuevas profundas del mundo. No obstante, también incluyen cuevas poco profundas con varios kilómetros de desarrollo, donde cada año se descubren nuevos pasajes subterráneos. Dichos pasajes incluyen 1,7 km de conductos hallados en la el Sistema del Hayéu del Osu, que ya alcanza los 3,5 km de desarrollo. Su desnivel máximo se incrementó hasta los 226 m al encontrarse una nueva entrada superior, llamada Torcana.Grupo Espeleológico Polifemo, EspañaGES Montañeiros Celtas, EspañaGrupo de Espeleología Diañu Burlón, EspañaGrupo d’Espeleoloxía Gorfolí, EspañaUnidad de Oviedo, Instituto Geológico y Minero de España, Españ

p62/SQSTM1 Fuels Melanoma Progression by Opposing mRNA Decay of a Selective Set of Pro-metastatic Factors

Modulators of mRNA stability are not well understood in melanoma, an aggressive tumor with complex changes in the transcriptome. Here we report the ability of p62/SQSTM1 to extend mRNA half-life of a spectrum of pro-metastatic factors. These include FERMT2 and other transcripts with no previous links to melanoma. Transcriptomic, proteomic, and interactomic analyses, combined with validation in clinical biopsies and mouse models, identified a selected set of RNA-binding proteins (RBPs) recruited by p62, with IGF2BP1 as a key partner. This p62-RBP interaction distinguishes melanoma from other tumors where p62 controls autophagy or oxidative stress. The relevance of these data is emphasized by follow-up analyses of patient prognosis revealing p62 and FERMT2 as adverse determinants of disease-free survival.M.S.S. is funded by grants from the Spanish Ministry of Economy and Innovation (SAF2014-56868-R; SAF2017-89533-R), the Asociación Española Contra el Cáncer (AECC), TV’13-20131430 (Marato de TV3), the Worldwide Cancer Research, an Established Investigator Award by the Melanoma Research Alliance (MRA), and a L'Oreal-Paris USA-MRA Team Science Award for Women in Scientific Research. M.S.S. also acknowledges a donation from “Fundación Causa Alexandra”, Spain. P.K. was a recipient of a predoctoral fellowship from Fundación La Caixa. E.R.-F. was funded by Fundación Mutua Madrileña (FMM-2013) and was a recipient of a fellowship from ‘‘Fundación Científica de la Asociación Española Contra el Cáncer”. The CNIO Proteomics Unit belongs to ProteoRed, PRB2-ISCIII, supported by grant PT13/0001. J.M. is also supported by Ramon y Cajal Programme (MINECO) RYC-2012-10651. J.L.R.-P. is funded by FIS 2014/173711/02568 and CIBERONC, and P.L.O.-R. by FIS 11/17592014/01784, from the Spanish Ministry of Health

RAB7 Controls Melanoma Progression by Exploiting a Lineage-Specific Wiring of the Endolysosomal Pathway

Although common cancer hallmarks are well established, lineage-restricted oncogenes remain less understood. Here, we report an inherent dependency of melanoma cells on the small GTPase RAB7, identified within a lysosomal gene cluster that distinguishes this malignancy from over 35 tumor types. Analyses in human cells, clinical specimens, and mouse models demonstrated that RAB7 is an early-induced melanoma driver whose levels can be tuned to favor tumor invasion, ultimately defining metastatic risk. Importantly, RAB7 levels and function were independent of MITF, the best-characterized melanocyte lineage-specific transcription factor. Instead, we describe the neuroectodermal master modulator SOX10 and the oncogene MYC as RAB7 regulators. These results reveal a unique wiring of the lysosomal pathway that melanomas exploit to foster tumor progression.M.S.S. is funded by Projects SAF2011-28317 and Consolider RNAREG from the Spanish Ministry of Economy and Innovation, R01CA125017 from the NIH, and a Team Science Award by the Melanoma Research Foundation. J.L.R.-P. and P.O.-R. are funded by grants FIS 11/025685 and FIS 11/1759, respectively, from the Spanish Ministry of Health. J.L.R.-P. was also supported by grant FMM-2008-106 of Fundación Mutua Madrileña, and P.O.-R. by Red Tematica de Investigacion Cooperativa en Cancer. D.A.-C. and E.P.-G. are recipients of Scientists in Training predoctoral fellowships from the Spanish Ministry of Science and Innovation. M.C. and P.K. are funded by predoctoral fellowships of Fundación La Caixa. E.R.-F. is the recipient of a postdoctoral fellowship from Fundación Científica de la Asociación Española Contra el Cáncer, and J.A.J. and H.-W.W. are funded by the American Cancer Society (RSG-12-076-01-LIB)

Análisis de iniciativas de disminución de tiempos no productivos en las empresas contratistas de preparación minera DET

Ingeniero Civil de Minas01/06/202

Relaciones entre los caracteres de comportamiento del toro de lidia

Resumen de la comunicación presentada al III Congreso Ibérico sobre Recursos Genéticos Animale

Genetic parameters of aggressiveness, ferocity and mobility in the fighting bull breed

Genetic parameter estimates for Aggressiveness, Ferocity and Mobility in the fighting bull bovine breed were obtained using the restricted maximum likelihood (REML) methodology applied to a multiple trait animal model. The year of birth and the sex of the animal were the environmental fixed effects considered in the model. Genetic trends were determined from the average predicted breeding value over the year of birth. The behavioural traits considered showed an important additive genetic component which can be used to modulate the phenotype expression by selection. Heritability values around 0.3 (0.286–0.362) for all traits could explain the successful empirical selection carried out on the Aggressiveness trait. Similarly, the lack of genetic correlation (P > 0.05) between all traits explains the absence of a correlated response for the Ferocity and Mobility traits.Paramètres génétiques pour les caractères Agressivité, Férocité et Mobilité chez le taureau de combat. Les estimations des paramètres génétiques pour les caractères Agressivité, Férocité et Mobilité chez le taureau de combat ont été obtenues en utilisant la méthode du maximum de vraisemblance restreint (REML) appliquée à un modèle animal multi caractères. L’année de naissance et le sexe ont été retenus comme effets fixes. Les tendances génétiques ont été déterminées à partir de la valeur additive moyenne au cours de l'année de naissance. Les caractères de comportement considérés montrent des composantes génétiques additives importantes qui peuvent être utilisées pour moduler l'expression phénotypique par sélection. Les valeurs d'héritabilité pour tous les caractères sont d’environ 0,3 (0,286–0,362) ce qui peut expliquer l’efficacité de la sélection empirique sur le caractère Agressivité. De la même manière, le manque de corrélation génétique (P > 0,05) entre tous les caractères explique l'absence d'une réponse corrélée pour les caractères Férocité et Mobilité

Metastatic risk and resistance to BRAF inhibitors in melanoma defined by selective allelic loss of <i>ATG5</i>

<p>Melanoma is a paradigm of aggressive tumors with a complex and heterogeneous genetic background. Still, melanoma cells frequently retain developmental traits that trace back to lineage specification programs. In particular, lysosome-associated vesicular trafficking is emerging as a melanoma-enriched lineage dependency. However, the contribution of other lysosomal functions such as autophagy to melanoma progression is unclear, particularly in the context of metastasis and resistance to targeted therapy. Here we mined a broad spectrum of cancers for a meta-analysis of mRNA expression, copy number variation and prognostic value of 13 core autophagy genes. This strategy identified heterozygous loss of <i>ATG5</i> at chromosome band 6q21 as a distinctive feature of advanced melanomas. Importantly, partial <i>ATG5</i> loss predicted poor overall patient survival in a manner not shared by other autophagy factors and not recapitulated in other tumor types. This prognostic relevance of <i>ATG5</i> copy number was not evident for other 6q21 neighboring genes. Melanocyte-specific mouse models confirmed that heterozygous (but not homozygous) deletion of <i>Atg5</i> enhanced melanoma metastasis and compromised the response to targeted therapy (exemplified by dabrafenib, a BRAF inhibitor in clinical use). Collectively, our results support ATG5 as a therapeutically relevant dose-dependent rheostat of melanoma progression. Moreover, these data have important translational implications in drug design, as partial blockade of autophagy genes may worsen (instead of counteracting) the malignant behavior of metastatic melanomas.</p