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The act of distinguishing oneself is a common practice in any complex society, where difference and hierarchy serve as regulatory bases. Focusing on the eighteenth and nineteenth centuries, this article examines the distinctive discourses of silversmith artisans, whether through individual or group initiatives, as a professional group of seemingly higher social standing. Using a wide range of documentary sources, from legal proceedings to personal wardrobes, this perspective applies a social approach to a subject rooted in cultural history, as these discourses must be evaluated in terms of their societal acceptance. La acción de distinguirse se impone como una práctica usual en toda sociedad compleja, en la que la diferen-cia y la jerarquía son sus bases reguladoras. Atendiendo a los siglos XVIII y XIX, el presente artículo se centra en los discursos distintivos de los artesanos plateros, ya sea desde iniciativas individuales o grupales, en tanto que grupo profesional portador de una aparente consideración social mayor. Sobre una amplia tipología documental que permite analizar desde procesos judiciales hasta los guardarropas personales, la presente perspectiva plantea la aplicación de un enfoque social a un tema vinculado a la historia cultural, en tanto que los discursos han de ser confrontados con su capacidad de aceptación.

El artesanado rural no ha asumido la atención que merece en la historiografía del retorno gremial, y son todavía muchos los interrogantes que falta por contestar. Asumido como uno de los desafíos actuales de la historia del trabajo manufacturero, en este artículo nos centramos en las platerías de dos agrociudades del sureste peninsular, Antequera y Lorca, con el objetivo identificar las pautas de comportamiento del artesanado en relación con el gremio, las formas de reproducción del oficio y la pluriactividad. Junto a ello, se hace conveniente la reconstrucción de trayectorias familiares en las que poder analizar todas estas cuestiones en el marco del proceso de cambio social; a fin de cuentas, arrogándole una capacidad de readaptación frente a unas sociedades rurales estereotipadas como inmóviles.

El artículo se centra en el estudio de las migraciones laborales artesanas entre los siglos XVIII y XIX, tomando como muestras los Colegio-Congregación de plateros del sureste peninsular. Así, se aporta una visión diferente, adscrita a mercados laborales más limitados, frente a los trabajos publicados hasta la fecha interesados en otros con mayor capacidad de atracción de mano de obra. Siguiendo planteamientos de la historia social de la población, a tenor de las posibilidades documentales ofrecidas fundamentalmente por recuentos poblacionales y escrituras notariales, se examinan los movimientos migratorios en función de la distancia recorrida: corta-media, donde se agrupa la existente en el entorno geográfico cercano u otras regiones hispánicas peninsulares, y larga distancia, adscrita únicamente al aporte extranjero. El objetivo, además de ponderar el aporte migrante en la reproducción del oficio e identificar los lugares de procedencia, avanza sobre la importancia cualitativa y las trayectorias de los emigrantes artesanos, dibujando una realidad diversa y compleja.

El artículo se centra en el estudio de las migraciones laborales artesanas entre los siglos XVIII y XIX, tomando como muestras los Colegio-Congregación de plateros del sureste peninsular. Así, se aporta una visión diferente, adscrita a mercados laborales más limitados, frente a los trabajos publicados hasta la fecha interesados en otros con mayor capacidad de atracción de mano de obra. Siguiendo planteamientos de la historia social de la población, a tenor de las posibilidades documentales ofrecidas fundamentalmente por recuentos poblacionales y escrituras notariales, se examinan los movimientos migratorios en función de la distancia recorrida: corta-media, donde se agrupa la existente en el entorno geográfico cercano u otras regiones hispánicas peninsulares, y larga distancia, adscrita únicamente al aporte extranjero. El objetivo, además de ponderar el aporte migrante en la reproducción del oficio e identificar los lugares de procedencia, avanza sobre la importancia cualitativa y las trayectorias de los emigrantes artesanos, dibujando una realidad diversa y compleja.

Pan‐cyclin‐dependent‐kinase (CDK) inhibitors are a new class of targeted therapies that can act on multiple CDKs, with dinaciclib being one of the most promising compounds. Although used as a monotherapy, an interesting approach could be to combine it with radiotherapy. Here, we show that dinaciclib increases radiosensitivity in some experimental models of lung and colon cancer (A549 or HCT 116) but not in others (H1299 or HT‐29). Dinaciclib did not alter serine‐protein kinase ATM signalling or cell cycle profiling after ionising‐radiation exposure, which have been described for other CDK inhibitors. Interestingly, in terms of apoptosis, although the combination renders a clear increase, no potentiation of the ionising‐radiation‐induced apoptosis was observed. Mechanistically, inhibition of CDK12 by dinaciclib diminishes BRCA1 expression, which decreases homologous recombination (HR) and probably promotes the nonhomologous end joining repair process (NHEJ), which ultimately promotes the induction of ionising‐radiation‐associated cellular senescence in a TP53‐dependent manner, explaining the lack of effect observed in some experimental models. In conclusion, our report proposes a molecular mechanism, based on the signalling axis CDK12–BRCA1, involved in this newly identified therapeutic effect of dinaciclib, although other players implicated in HR should not be discarded. In addition, our data provide a rationale for more selective and personalised chemo/radiotherapy treatment according to the genetic background of the tumour. Dinaciclib blocks CDK12 activity, leading to downregulation of BRCA1, and probably other proteins involved in homologous recombination, promoting nonhomologous end joining. In this scenario, the presence of ionising radiation triggers a p53‐dependent senescent response that yields increased radiosensitivity.

This research was partially supported by the Grant BIO2010-18239 from the Comisión Interministerial de Ciencia y Tecnología and Fondo Europeo de Desarrollo Regional (Spain), and by Iden Biotechnology S.L. G.A. acknowledges a fellowship from the Public University of Navarra.

Background X-linked hypophosphatemia (XLH) is a hereditary rare disease caused by loss-of-function mutations in PHEX gene leading tohypophosphatemia and high renal loss of phosphate. Rickets and growth retardation are the major manifestations of XLH in children, but there is a broad phenotypic variability. Few publications have reported large series of patients. Current data on the clinical spectrum of the disease, the correlation with the underlying gene mutations, and the long-term outcome of patients on conventional treatment are needed, particularly because of the recent availability of new specific medications to treat XLH. Results The RenalTube database was used to retrospectively analyze 48 Spanish patients (15 men) from 39 different families, ranging from 3 months to 8 years and 2 months of age at the time of diagnosis (median age of 2.0 years), and with XLH confirmed by genetic analysis. Bone deformities, radiological signs of active rickets and growth retardation were the most common findings at diagnosis. Mean (± SEM) height was − 1.89 ± 0.19 SDS and 55% (22/40) of patients had height SDS below—2. All cases had hypophosphatemia, serum phosphate being − 2.81 ± 0.11 SDS. Clinical manifestations and severity of the disease were similar in both genders. No genotype—phenotype correlation was found. Conventional treatment did not attenuate growth retardation after a median follow up of 7.42 years (IQR = 11.26; n = 26 patients) and failed to normalize serum concentrations of phosphate. Eleven patients had mild hyperparathyroidism and 8 patients nephrocalcinosis. Conclusions This study shows that growth retardation and rickets were the most prevalent clinical manifestations at diagnosis in a large series of Spanish pediatric patients with XLH confirmed by mutations in the PHEX gene. Traditional treatment with phosphate and vitamin D supplements did not improve height or corrected hypophosphatemia and was associated with a risk of hyperparathyroidism and nephrocalcinosis. The severity of the disease was similar in males and females.

To fully clarify the role of Mitogen Activated Protein Kinase in the therapeutic response to Sorafenib in Renal Cell Carcinoma as well as the cell death mechanism associated to this kinase inhibitor, we have evaluated the implication of several Mitogen Activated Protein Kinases in Renal Cell Carcinoma-derived cell lines. An experimental model of Renal Cell Carcinoma-derived cell lines (ACHN and 786-O cells) was evaluated in terms of viability by MTT assay, induction of apoptosis by caspase 3/7 activity, autophagy induction by LC3 lipidation, and p62 degradation and kinase activity using phospho-targeted antibodies. Knock down of ATG5 and ERK5 was performed using lentiviral vector coding specific shRNA. Our data discard Extracellular Regulated Kinase 1/2 and 5 as well as p38 Mitogen Activated Protein Kinase pathways as mediators of Sorafenib toxic effect but instead indicate that the inhibitory effect is exerted through the PI3K/Akt signalling pathway. Furthermore, we demonstrate that inhibition of Akt mediates cell death associated to Sorafenib without caspase activation, and this is consistent with the induction of autophagy, as indicated by the use of pharmacological and genetic approaches. The present report demonstrates that Sorafenib exerts its toxic effect through the induction of autophagy in an Akt-dependent fashion without the implication of Mitogen Activated Protein Kinase. Therefore, our data discard the use of inhibitors of the RAF-MEK-ERK1/2 signalling pathway in RCC and support the use of pro-autophagic compounds, opening new therapeutic opportunities for Renal Cell Carcinoma.