Function of Armcx3 and Armc10/SVH genes in the regulation of progenitor proliferation and neural differentiation in the chicken spinal cord

The eutherian X-chromosome specific family of Armcx genes has been described as originating by retrotransposition from Armc10/SVH, a single Arm-containing somatic gene. Armcx3 and Armc10/SVH are characterized by high expression in the central nervous system and they play an important role in the regulation of mitochondrial distribution and transport in neurons. In addition, Armcx/Arm10 genes have several Armadillo repeats in their sequence. In this study we address the potential role of this gene family in neural development by using the chick neural tube as a model. We show that Armc10/SVH is expressed in the chicken spinal cord, and knocking-down Armc10/SVH by sh-RNAi electroporation in spinal cord reduces proliferation of neural precursor cells (NPCs). Moreover, we analyzed the effects of murine Armcx3 and Armc10 overexpression, showing that both proteins regulate progenitor proliferation, while Armcx3 overexpression also specifically controls neural maturation. We show that the phenotypes found following Armcx3 overexpression require its mitochondrial localization, suggesting a novel link between mitochondrial dynamics and regulation of neural development. Furthermore, we found that both Armcx3 and Armc10 may act as inhibitors of Wnt-β-catenin signaling. Our results highlight both common and differential functions of Armcx/Armc10 genes in neural development in the spinal cord.This work was supported by grants from Spanish MINECO (SAF2013-42445R), CIBERNED (ISCIII) and La Marató de TV3 Foundation to ES; Spanish MINECO (BFU2010-21507) to FU; BFU2013-46477-P to EMPeer Reviewe

Alendronate and etidronate do not regulate interleukin 6 and 11 synthesis in normal human osteoblasts in culture

Bisphosphonates exert a potent inhibitory effect on bone resorption. Several studies have been performed, with contradictory results, to ascertain whether the effect of bisphosphonates on osteoclasts could be produced, at least in part, by modulation of the synthesis of resorption-promoting factors by osteoblasts. The aim of this study was to evaluate the effect of etidronate (10)4–10)9 M) and alendronate (10)7–10)12 M) on the production of IL-6 and IL-11 using human osteoblast cultures. Cytokines were quantified by ELISA, and mRNA expression was tested. Treatment with alendronate and etidronate had no effect on the synthesis of IL-6 or IL-11, and IL-6 and IL-11 mRNA levels. These results were obtained both in nonstimulated cultures and in cultures stimulated by means of TNF-a, IL-1b, and TNF-a+IL-1b, with or without FCS. In conclusion, a possible indirect osteoclast-mediated effect of alendronate and etidronate on bone resorption would not be exerted through reduction in osteoblastic synthesis of IL-6 and IL-11.Postprint (published version

The non-canonical Wnt/PKC pathway regulates mitochondrial dynamics through degradation of the ARM-like domain-containing protein Alex3

The regulation of mitochondrial dynamics is vital in complex cell types, such as neurons, that transport and localize mitochondria in high energy-demanding cell domains. The Armcx3 gene encodes a mitochondrial-targeted protein (Alex3) that contains several arm-like domains. In a previous study we showed that Alex3 protein regulates mitochondrial aggregation and trafficking. Here we studied the contribution of Wnt proteins to the mitochondrial aggregation and dynamics regulated by Alex3. Overexpression of Alex3 in HEK293 cells caused a marked aggregation of mitochondria, which was attenuated by treatment with several Wnts. We also found that this decrease was caused by Alex3 degradation induced by Wnts. While the Wnt canonical pathway did not alter the pattern of mitochondrial aggregation induced by Alex3, we observed that the Wnt/PKC non-canonical pathway regulated both mitochondrial aggregation and Alex3 protein levels, thereby rendering a mitochondrial phenotype and distribution similar to control patterns. Our data suggest that the Wnt pathway regulates mitochondrial distribution and dynamics through Alex3 protein degradation

Function of Armcx3 and Armc10/svh genes in the regulation of progenitor proliferation and neural differentiation in the chicken spinal cord

The eutherian X-chromosome specific family of Armcx genes has been described asoriginating by retrotransposition from Armc10/SVH, a single Arm-containing somaticgene. Armcx3 and Armc10/SVH are characterized by high expression in the centralnervous system and they play an important role in the regulation of mitochondrialdistribution and transport in neurons. In addition, Armcx/Arm10 genes have severalArmadillo repeats in their sequence. In this study we address the potential role of thisgene family in neural development by using the chick neural tube as a model. Weshow that Armc10/SVH is expressed in the chicken spinal cord, and knocking-downArmc10/SVH by sh-RNAi electroporation in spinal cord reduces proliferation of neuralprecursor cells (NPCs). Moreover, we analyzed the effects of murine Armcx3 andArmc10 overexpression, showing that both proteins regulate progenitor proliferation,while Armcx3 overexpression also specifically controls neural maturation. We showthat the phenotypes found following Armcx3 overexpression require its mitochondriallocalization, suggesting a novel link between mitochondrial dynamics and regulation ofneural development. Furthermore, we found that both Armcx3 and Armc10 may act asinhibitors of Wnt-β-catenin signaling. Our results highlight both common and differentialfunctions of Armcx/Armc10 genes in neural development in the spinal cord

Análisis del discurso que maneja la serie española la casa de papel en sus dos primeras temporadas, como símbolo de resistencia en contra del sistema

The research work analyzes the discourse of the first two seasons of "La Casa de Papel", which were released in 2017 through the Spanish channel Antena 3. With the research and the general objective, the discourse is analyzed to know if it responds to a message of resistance against the system. In the specific objectives it is proposed: to identify the dialogues or scenes that show some indication of resistance. The research uses a qualitative methodology with an explanatory scope, being the main data collection tools four content analysis cards. The results obtained show that in the dialogues and actions of the main characters there is an essence of resistance. In conclusion, it is determined that the series handles resistance well in its characters, dialogues and symbols, but not in the plot.El trabajo de investigación analiza el discurso de las dos primeras temporadas de “La Casa de Papel”, que fueron estrenadas en el año 2017 a través de la cadena española Antena 3. Con la investigación y el objetivo general se analiza el discurso para conocer si responde a un mensaje de resistencia en contra del sistema. En los objetivos específicos se plantea: identificar los diálogos o escenas que manifiesten algún indicio de resistencia. En la investigación se utiliza una metodología cualitativa con alcance explicativo, siendo las principales herramientas de recolección de datos cuatro fichas de análisis de contenido. Los resultados obtenidos demuestran que, en los diálogos y accionar por parte los personajes protagonistas hay esencia de resistencia. En conclusión se determina que la serie maneja bien la resistencia en sus personajes, diálogos y símbolos; pero, en cuanto a la trama no

Blockade of the SNARE Protein Syntaxin 1 Inhibits Glioblastoma Tumor Growth

Glioblastoma (GBM) is the most prevalent adult brain tumor, with virtually no cure, and with a median overall survival of 15 months from diagnosis despite of the treatment. SNARE proteins mediate membrane fusion events in cells and are essential for many cellular processes including exocytosis and neurotransmission, intracellular trafficking and cell migration. Here we show that the blockade of the SNARE protein Syntaxin 1 (Stx1) function impairs GBM cell proliferation. We show that Stx1 loss-of-function in GBM cells, through ShRNA lentiviral transduction, a Stx1 dominant negative and botulinum toxins, dramatically reduces the growth of GBM after grafting U373 cells into the brain of immune compromised mice. Interestingly, Stx1 role on GBM progression may not be restricted just to cell proliferation since the blockade of Stx1 also reduces in vitro GBM cell invasiveness suggesting a role in several processes relevant for tumor progression. Altogether, our findings indicate that the blockade of SNARE proteins may represent a novel therapeutic tool against GB

EDUCACIÓN TECNOLÓGICA E INCLUSIVA PARA FORTALECER EL DESARROLLO DE HABILIDADES COGNITIVAS EN GRUPOS ANCESTRALES TSÁCHILAS

Computer-based teaching-learning processes are of great importance at present for the strengthening of cognitive skills in ancestral peoples, as well as the conservation of ethnic identity where there are still United Educational Units such as the Patricio Romero Barberis Educational Center from the Otongo Mapalí commune in Santo Domingo-Ecuador. The present project, more than an investigation, tries to implement new educational software alternatives in order to be an aid to teachers and children for the development and strengthening of cognitive abilities in ethnic groups of a Tsáchila community. The research approach is qualitative type, based on a documentary design which allows to have a scope of descriptive research linked to the elements that make up educational software, it is intended for children between the second and fourth year of basic general education of the commune mentioned above. The Adobe Animate platform was used as development tools for the design or layout part and for programming the Action Script 3.0 language under the Object Oriented paradigm. As a result, four modules are presented in which different cognitive abilities of thinking are organized through practical exercises.Los procesos de enseñanza aprendizaje basados en computación son de gran importancia en la actualidad para el fortalecimiento de habilidades cognitivas en los pueblos ancestrales, así como la conservación de la identidad étnica donde aún existes Unidades Educativas Unidocente como es el caso de Centro Educativo Patricio Romero Barberis de la comuna Otongo Mapalí en Santo Domingo-Ecuador. El presente proyecto, más que una investigación, trata de implementar nuevas alternativas de software educativo con el objeto de ser una ayuda a docentes y niños para el desarrollo y fortalecimiento de habilidades cognitivas en grupos étnicos de una comunidad Tsáchila. El enfoque de investigación es tipo cualitativo, basado en un diseño documental lo que permite tener un alcance de investigación descriptiva vinculado a los elementos que compone software educativo, el mismo está destinado para niños de entre segundo y cuarto año de educación general básica de la comuna antes mencionada. Como herramientas de desarrollo se utilizó la plataforma de Adobe Animate para la parte de diseño o maquetación y para la programación el lenguaje Action Script 3.0 bajo el paradigma Orientado a objetos. Como resultado se presenta cuatro módulos en la cual se organizan a través de ejercicios prácticos, diferentes habilidades cognitivas del pensamiento

Blockade of the SNARE protein syntaxin 1 inhibits glioblastoma tumor growth

Glioblastoma (GBM) is the most prevalent adult brain tumor, with virtually no cure, and with a median overall survival of 15 months from diagnosis despite of the treatment. SNARE pro- teins mediate membrane fusion events in cells and are essential for many cellular process- es including exocytosis and neurotransmission, intracellular trafficking and cell migration. Here we show that the blockade of the SNARE protein Syntaxin 1 (Stx1) function impairs GBM cell proliferation. We show that Stx1 loss-of-function in GBM cells, through ShRNA lentiviral transduction, a Stx1 dominant negative and botulinum toxins, dramatically reduces the growth of GBM after grafting U373 cells into the brain of immune compromised mice. In- terestingly, Stx1 role on GBM progression may not be restricted just to cell proliferation since the blockade of Stx1 also reduces in vitro GBM cell invasiveness suggesting a role in several processes relevant for tumor progression. Altogether, our findings indicate that the blockade of SNARE proteins may represent a novel therapeutic tool against GBM

The Armc10/SVH gene: Genome context, regulation of mitochondrial dynamics and protection against Aβ-induced mitochondrial fragmentation

Mitochondrial function and dynamics are essential for neurotransmission, neural function and neuronal viability. Recently, we showed that the eutherian-specific Armcx gene cluster (Armcx1-6 genes), located in the X chromosome, encodes for a new family of proteins that localise to mitochondria, regulating mitochondrial trafficking. The Armcx gene cluster evolved by retrotransposition of the Armc10 gene mRNA, which is present in all vertebrates and is considered to be the ancestor gene. Here we investigate the genomic organisation, mitochondrial functions and putative neuroprotective role of the Armc10 ancestor gene. The genomic context of the Armc10 locus shows considerable syntenic conservation among vertebrates, and sequence comparisons and CHIP-data suggest the presence of at least three conserved enhancers. We also show that the Armc10 protein localises to mitochondria and that it is highly expressed in the brain. Furthermore, we show that Armc10 levels regulate mitochondrial trafficking in neurons, but not mitochondrial aggregation, by controlling the number of moving mitochondria. We further demonstrate that the Armc10 protein interacts with the KIF5/Miro1-2/Trak2 trafficking complex. Finally, we show that overexpression of Armc10 in neurons prevents A beta-induced mitochondrial fission and neuronal death. Our data suggest both conserved and differential roles of the Armc10/Armcx gene family in regulating mitochondrial dynamics in neurons, and underscore a protective effect of the Armc10 gene against A beta-induced toxicity. Overall, our findings support a further degree of regulation of mitochondrial dynamics in the brain of more evolved mammals