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Mansilla A.,Instituto Cajal | Martin F.A.,Instituto Cajal | Martin D.,Institute Biologia Evolutiva | Ferrus A.,Instituto Cajal
Cell Death and Differentiation | Year: 2016

The active form of the Drosophila steroid hormone ecdysone, 20-hydroxyecdysone (20E), binds the heterodimer EcR/USP nuclear receptor to regulate target genes that elicit proliferation, cell death and differentiation during insect development. Although the 20E effects are relatively well known, the physiological relevance of its receptors remains poorly understood. We show here that the prothoracic gland (PG), the major steroid-producing organ of insect larvae, requires EcR and USP to survive in a critical period previous to metamorphosis, and that this requirement is 20E-independent. The cell death induced by the downregulation of these receptors involves the activation of the JNK-encoding basket gene and it can be rescued by upregulating EcR isoforms which are unable to respond to 20E. Also, while PG cell death prevents ecdysone production, blocking hormone synthesis or secretion in normal PG does not lead to cell death, demonstrating further the ecdysone-independent nature of the receptor-deprivation cell death. In contrast to PG cells, wing disc or salivary glands cells do not require these receptors for survival, revealing their cell and developmental time specificity. Exploring the potential use of this feature of steroid receptors in cancer, we assayed tumor overgrowth induced by altered yorkie signaling. This overgrowth is suppressed by EcR downregulation in PG, but not in wing disc, cells. The mechanism of all these cell death features is based on the transcriptional regulation of reaper. These novel and context-dependent functional properties for EcR and USP receptors may help to understand the heterogeneous responses to steroid-based therapies in human pathologies. © 2016 Macmillan Publishers Limited.


Verdu-Ricoy J.,CSIC - National Museum of Natural Sciences | Carranza S.,Institute Biologia Evolutiva | Salvador A.,CSIC - National Museum of Natural Sciences | Busack S.D.,North Carolina State Museum of Natural science | Diaz J.A.,Complutense University of Madrid
Amphibia Reptilia | Year: 2010

Relationships among Psammodromus algirus populations from the Iberian Peninsula and North Africa, including recently described P. jeanneae and P. manuelae, were estimated from mitochondrial DNA gene sequences. This enlarged data set confirmed the presence of two divergent eastern and western mitochondrial DNA lineages on the Iberian Peninsula, the distributions for which are separated by a narrow zone of contact across the centre of the Peninsula. Paratypes of P. jeanneae and topotypes of P. manuelae represent southern and northern clades of the western lineage, respectively, making P. algirus paraphyletic. This, together with the low level of allozymic and mitochondrial DNA substructuring within western populations, is not sufficient to retain P. jeanneae and P. manuelae as valid species, and we relegate them to the status of junior synonyms of P. algirus. © 2010 Brill Academic Publishers.


Rosas A.,CSIC - National Museum of Natural Sciences | Estalrrich A.,CSIC - National Museum of Natural Sciences | Garcia-Tabernero A.,CSIC - National Museum of Natural Sciences | Huguet R.,Rovira i Virgili University | And 10 more authors.
Cuaternario y Geomorfologia | Year: 2015

The archaeological project in the Gallery of the Osario of the cave of El Sidrón (Asturias, Spain) has recently concluded after 13 field seasons of detailed, methodical excavation. We present here a summary of the lines of research and the paleoanthropological studies carried out to date, as well as a brief perspective of the ongoing investigations. More than 2550 neandertal fossil remains have been recovered from this singular deposit, together with 400 pieces of Mousterian lithic industry, and less than 60 non-human remains. Sedimentological, taphonomic and structural analyses of the karst clarify that this fossil assemblage is in a secondary position and comes by mudflow from a gallery/shelter located in a superior level of the karst. All the skeletal parts are represented, and 13 individuals have been identified: 7 adults (3 males, 4 females), 3 adolescents (2 males, 1 female), 2 male juveniles and an infant. The El Sidrón collection constitutes the most numerous and diverse neandertal sample of the Iberian Peninsula, allowing systemic studies on tempo and modo of appearance of the derived characters in the neandertal lineage. The wide undertaken paleobiological research program includes the study of the different levels of biological organization, from demographic and evolutionary dynamics to molecular aspects. With regard to the latter, the extraction of DNA sequences has played a central role, with the characterization of the mt-DNA haplotype of 12 individuals, and with the inclusion of samples from El Sidrón in the Neandertal Genome and Exome projects. Results from the genetic and osteological studies define El Sidrón neandertals as a homogenous group, with narrow kinship bonds between their individuals. Finally, the numerous evidences of human-induced treatment of the bones make of El Sidrón a paradigmatic example of practices of cannibalism between the neandertals. © 2015, Asociacion Espanola para el Estudio del Cuaternario (AEQUA). All rights reserved.


PubMed | Instituto Cajal and Institute Biologia Evolutiva
Type: Journal Article | Journal: Cell death and differentiation | Year: 2016

The active form of the Drosophila steroid hormone ecdysone, 20-hydroxyecdysone (20E), binds the heterodimer EcR/USP nuclear receptor to regulate target genes that elicit proliferation, cell death and differentiation during insect development. Although the 20E effects are relatively well known, the physiological relevance of its receptors remains poorly understood. We show here that the prothoracic gland (PG), the major steroid-producing organ of insect larvae, requires EcR and USP to survive in a critical period previous to metamorphosis, and that this requirement is 20E-independent. The cell death induced by the downregulation of these receptors involves the activation of the JNK-encoding basket gene and it can be rescued by upregulating EcR isoforms which are unable to respond to 20E. Also, while PG cell death prevents ecdysone production, blocking hormone synthesis or secretion in normal PG does not lead to cell death, demonstrating further the ecdysone-independent nature of the receptor-deprivation cell death. In contrast to PG cells, wing disc or salivary glands cells do not require these receptors for survival, revealing their cell and developmental time specificity. Exploring the potential use of this feature of steroid receptors in cancer, we assayed tumor overgrowth induced by altered yorkie signaling. This overgrowth is suppressed by EcR downregulation in PG, but not in wing disc, cells. The mechanism of all these cell death features is based on the transcriptional regulation of reaper. These novel and context-dependent functional properties for EcR and USP receptors may help to understand the heterogeneous responses to steroid-based therapies in human pathologies.

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