Dual activation of pathways regulated by steroid receptors and peptide growth factors in primary prostate cancer revealed by Factor Analysis of microarray data

BACKGROUND: We use an approach based on Factor Analysis to analyze datasets generated for transcriptional profiling. The method groups samples into biologically relevant categories, and enables the identification of genes and pathways most significantly associated to each phenotypic group, while allowing for the participation of a given gene in more than one cluster. Genes assigned to each cluster are used for the detection of pathways predominantly activated in that cluster by finding statistically significant associated GO terms. We tested the approach with a published dataset of microarray experiments in yeast. Upon validation with the yeast dataset, we applied the technique to a prostate cancer dataset. RESULTS: Two major pathways are shown to be activated in organ-confined, non-metastatic prostate cancer: those regulated by the androgen receptor and by receptor tyrosine kinases. A number of gene markers (HER3, IQGAP2 and POR1) highlighted by the software and related to the later pathway have been validated experimentally a posteriori on independent samples. CONCLUSION: Using a new microarray analysis tool followed by a posteriori experimental validation of the results, we have confirmed several putative markers of malignancy associated with peptide growth factor signalling in prostate cancer and revealed others, most notably ERRB3 (HER3). Our study suggest that, in primary prostate cancer, HER3, together or not with HER4, rather than in receptor complexes involving HER2, could play an important role in the biology of these tumors. These results provide new evidence for the role of receptor tyrosine kinases in the establishment and progression of prostate cancer

Dual activation of pathways regulated by steroid receptors and peptide growth factors in primary prostate cancer revealed by Factor Analysis of microarray data

BACKGROUND: We use an approach based on Factor Analysis to analyze datasets generated for transcriptional profiling. The method groups samples into biologically relevant categories, and enables the identification of genes and pathways most significantly associated to each phenotypic group, while allowing for the participation of a given gene in more than one cluster. Genes assigned to each cluster are used for the detection of pathways predominantly activated in that cluster by finding statistically significant associated GO terms. We tested the approach with a published dataset of microarray experiments in yeast. Upon validation with the yeast dataset, we applied the technique to a prostate cancer dataset. RESULTS: Two major pathways are shown to be activated in organ-confined, non-metastatic prostate cancer: those regulated by the androgen receptor and by receptor tyrosine kinases. A number of gene markers (HER3, IQGAP2 and POR1) highlighted by the software and related to the later pathway have been validated experimentally a posteriori on independent samples. CONCLUSION: Using a new microarray analysis tool followed by a posteriori experimental validation of the results, we have confirmed several putative markers of malignancy associated with peptide growth factor signalling in prostate cancer and revealed others, most notably ERRB3 (HER3). Our study suggest that, in primary prostate cancer, HER3, together or not with HER4, rather than in receptor complexes involving HER2, could play an important role in the biology of these tumors. These results provide new evidence for the role of receptor tyrosine kinases in the establishment and progression of prostate cancer

Área de puesta del listado, Katsuwonus pelamis (Scombridae), en el Mediterráneo occidental

Skipjack is an important commercial species with a tropical distribution, although captures in the Mediterranean Sea have been recorded for decades. The western Mediterranean Sea, specifically the Balearic Sea, is a spawning area for several tuna species. We hypothesized that the western Mediterranean warming in the last few decades could lead to the expansion of skipjack tuna spawning areas from tropical areas to the Mediterranean Sea. We analysed 454 individuals (41.8-81 cm straight fork length) caught by sport fishing vessels in offshore trolling championships in Spanish Mediterranean waters during summer months from 2014 to 2019. Analysis of the gonadosomatic index and microscopic examination of the ovaries (n=192) showed that the skipjack is reproductively active in the western Mediterranean, particularly in the Balearic Sea. These results indicate that the skipjack has expanded its distribution and spawning area from tropical waters to the Mediterranean, probably owing to the gradual warming detected in the area in the last few decades. This new spawning activity in the area should be monitored in the near future to study the possible impact on other tuna species that share the distribution range and spawning area with skipjack tuna in the western Mediterranean.El listado (Katsuwonus pelamis) es una especie muy importante a nivel comercial. Aunque su distribución es tropical, desde hace décadas se registran capturas en el Mediterráneo. El Mediterráneo occidental, concretamente el mar Balear, es zona de puesta de varias especies de túnidos. Este trabajo planteó la hipótesis de que el calentamiento registrado en las últimas décadas en el Mediterráneo occidental podría producir la expansión de las áreas de puesta del Listado desde las zonas tropicales hasta el mar Mediterráneo. Analizamos 454 ejemplares (41,8-81 cm SFL) capturados por embarcaciones de pesca recreativa en campeonatos de curricán de altura durante los meses de verano de 2014 a 2019 en aguas del Mediterráneo español. El análisis del Índice Gonadosomático y el análisis microscópico de los ovarios (n=192) mostraron que la especie es reproductivamente activa en el Mediterráneo occidental, particularmente en el mar Balear. Estos resultados indican que el Listado ha ampliado su área de distribución y puesta desde aguas tropicales hasta el Mediterráneo, probablemente debido al calentamiento gradual detectado en la zona en las últimas décadas. Además, es de interés realizar un seguimiento de esta nueva actividad de puesta en un futuro próximo para estudiar el posible impacto sobre otras especies de túnidos con las que comparte tanto área de distribución como zona de puesta en el Mediterráneo occidental

Dark Matter Searches Using NaI(Tl) at the Canfranc Underground Laboratory: Past, Present and Future

Sodium Iodide Thallium doped (NaI(Tl)) scintillation detectors have been applied to the direct searches for dark matter since the 1980s and have produced one of the most challenging results in the field-the observation by the DAMA/LIBRA collaboration of an annual modulation in the detection rate for more than twenty cycles. This result is very difficult to reconcile with negative results derived from other experiments using a large variety of target materials and detection techniques. However, it has been neither confirmed nor refuted in a model independent way up to the present. Such a model independent test of the DAMA/LIBRA result is the goal of the ANAIS-112 experiment, presently in the data taking phase at the Canfranc Underground Laboratory in Spain. ANAIS-112 design and operation leans on the expertise acquired at the University of Zaragoza in direct searches for Dark Matter particles using different targets and techniques and in particular using NaI(Tl) scintillation detectors for about thirty years, which are reviewed in the first section of this manuscript. In addition to presenting the status and more recent results of the ANAIS-112 experiment, open research lines, continuing this effort, will be presented

Changes in hematological, biochemical, and blood gases prameters in response to progressive inclusion of nitrate in the diet of Holstein calves

Background and Aim: Nitrate (NO3-) reduces enteric methane emissions and could be a source of non-protein nitrogen in ruminant feeds. Nonetheless, it has a potential toxic effect that could compromise animal health and production. The purpose of this study was to determine the effects of progressive inclusion of NO3- in the diet on the hematological, biochemical, and blood gases parameters, in turn, the effects on feed intake and live weight gain (LWG) in Holstein calves. Materials and Methods: Eighteen Holstein heifers and steers (nine animals/treatment) were maintained in individual pens for 45 days. Animals were randomly allocated to either a control or nitrate diet (ND) (containing 15 g of NO3-/kg of dry matter [DM]). The biochemical parameters and blood gases were analyzed only in the NO3- group on days: -1, 1, 7, 13, 19, and 25 corresponding to 0, 20, 40, 60, 80, and 100% of the total inclusion of NO3- in the diet, respectively. In addition, DM intake (DMI) and LWG were evaluated among dietary treatments. Results: Feeding the ND did not influence DMI or LWG (p>0.05). Methemoglobin (MetHb) and deoxyhemoglobin increased according to the NO3- concentrations in the diet (p0.05). However, glucose, urea, aspartate aminotransferase (AST), and retinol concentrations increased (p<0.05) according to the NO3- concentrations in the diet.Instituto de PatobiologíaFil: Ortiz Chura, Abimael. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patobiología; ArgentinaFil: Ortiz Chura, Abimael. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Marcoppido, Gisela Ariana. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patobiología; ArgentinaFil: Marcoppido, Gisela Ariana. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Gere, José. Universidad Tecnológica Nacional. División Investigación y Desarrollo de Ingenierías; ArgentinaFil: Gere, José. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Depetris, Gustavo. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Balcarce; ArgentinaFil: Stefañuk Bahamonte, Francisco José. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Balcarce; ArgentinaFil: Trangoni, Marcos David. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular. ArgentinaFil: Trangoni, Marcos David. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cravero, Silvio Lorenzo Pedro. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; ArgentinaFil: Cravero, Silvio Lorenzo Pedro. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Faverin, Claudia. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Balcarce; ArgentinaFil: Cataldi, Angel Adrian. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Agrobiotecnología y Biología Molecular; ArgentinaFil: Cataldi, Angel Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ceron Cucchi, Maria Esperanza. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Patobiología; ArgentinaFil: Ceron Cucchi, Maria Esperanza. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Planeamiento estratégico de la empresa DS - periodo 2019-2022

El presente trabajo de investigación analiza el caso de la empresa Delta Signal dentro de la industria de venta de autopartes electrónicas, en un contexto de márgenes bajos y un entorno altamente competitivo, y busca plantear un plan estratégico que permita mejorar la situación de la empresa y hacerla sostenible en el tiempo. Delta Signal es una empresa de venta de autopartes electrónicas que, a través del negocio business-to-business (B2B) con empresas fabricantes y ensambladoras de autos en el mercado de los Estados Unidos, ha llegado a tener prestigio en cuanto a innovación y calidad de sus productos. Sin embargo, aún no cuentan con una rentabilidad que le permita ser sostenible en el tiempo. Se espera que, a través de la implementación de las propuestas basadas en el análisis del entorno, el análisis interno y las estrategias alineadas con las ventajas diferenciales de la empresa, entre otros aspectos a tomar en cuenta, se logre que Delta Signal crezca de manera rentable, a pesar de la competencia existente y los márgenes bajos del mercado

New Trends and Challenges in Condition Monitoring Strategies for Assessing the State-of-charge in Batteries

Condition monitoring strategies play an important key role to ensure the proper operation and/or working conditions in electrical, mechanical, and electronic systems; in this sense, condition monitoring methods are commonly implemented aiming to avoid undesired breakdowns and are also implemented to extend the useful life of the evaluated elements as much as possible. Therefore, the objective of this work is to report the new trends and challenges related to condition monitoring strategies for assessing the state-of-charge in batteries under the Industry 4.0 framework. Specifically, this work is focused on the analysis of those signal processing and artificial intelligence techniques that are implemented in experimental and model-based assessing approaches. With this work, important aspects may be highlighted as well as the conclusions and prospects may be included for the development trend of condition monitoring strategies to assess and ensure the state-of-charge in batteries

Hypoxia Promotes Glycogen Accumulation through Hypoxia Inducible Factor (HIF)-Mediated Induction of Glycogen Synthase 1

When oxygen becomes limiting, cells reduce mitochondrial respiration and increase ATP production through anaerobic fermentation of glucose. The Hypoxia Inducible Factors (HIFs) play a key role in this metabolic shift by regulating the transcription of key enzymes of glucose metabolism. Here we show that oxygen regulates the expression of the muscle glycogen synthase (GYS1). Hypoxic GYS1 induction requires HIF activity and a Hypoxia Response Element within its promoter. GYS1 gene induction correlated with a significant increase in glycogen synthase activity and glycogen accumulation in cells exposed to hypoxia. Significantly, knockdown of either HIF1α or GYS1 attenuated hypoxia-induced glycogen accumulation, while GYS1 overexpression was sufficient to mimic this effect. Altogether, these results indicate that GYS1 regulation by HIF plays a central role in the hypoxic accumulation of glycogen. Importantly, we found that hypoxia also upregulates the expression of UTP:glucose-1-phosphate urydylyltransferase (UGP2) and 1,4-α glucan branching enzyme (GBE1), two enzymes involved in the biosynthesis of glycogen. Therefore, hypoxia regulates almost all the enzymes involved in glycogen metabolism in a coordinated fashion, leading to its accumulation. Finally, we demonstrated that abrogation of glycogen synthesis, by knock-down of GYS1 expression, impairs hypoxic preconditioning, suggesting a physiological role for the glycogen accumulated during chronic hypoxia. In summary, our results uncover a novel effect of hypoxia on glucose metabolism, further supporting the central importance of metabolic reprogramming in the cellular adaptation to hypoxia

Targeting ribosomal G-quadruplexes with naphthalene-diimides as RNA polymerase I inhibitors for colorectal cancer treatment

17 pags., 6 figs., 2 tabs.Sanchez-Martin et al. report a mode of action for naphthalene-diimides, a well-known class of G-quadruplexes ligands. Their work provides evidence of naphthalene-diimides targeting G-quadruplexes in ribosomal DNA, inducing a blockade of RNA polymerase I-mediated transcription and cell death. These compounds could be exploited in colorectal cancer treatment.This work was supported by the European Commission (TAR- BRAINFECT to J.A.G.-S.) and the National Institutes of Health (GM084946 to D.A.S.). The Government of Spain granted with PhD fellowships FPU16/ 05822 to V.S.-M. and FPU17/05413 to A.S.-L. The University of Almeria granted with PhD fellowship to M.O.-G. Funding for open access charge: Eu- ropean Commissio