Modelos celulares de enfermedad mitocondrial causada por mutaciones en POLG

Las enfermedades mitocondriales constituyen un grupo de trastornos originados por una deficiente síntesis de ATP por el sistema OXPHOS. Mutaciones en la DNA polimerasa mitocondrial gamma (POLG), única DNA polimerasa mitocondrial humana conocida y esencial para la replicación y reparación del DNA mitocondrial, producen diversas enfermedades mitocondriales con manifestaciones clínicas muy heterogéneas. Sin embargo, estas mutaciones tienen en común la presencia de diversos grados de afectación neuronal, que lleva a neurodegeneración. A pesar de que el cerebro representa solo el 2 % del peso corporal, consume el 20 % de la energía corporal. La mayor parte de esta energía es consumida por las neuronas y es el sistema OXPHOS el que la produce. Con el objetivo final de caracterizar el efecto de mutaciones patológicas de la DNA polimerasa mitocondrial gamma en la diferenciación neuronal y en el sistema OXPHOS de neuronas maduras, en este trabajo, se han caracterizado a nivel genético, molecular y funcional líneas celulares derivadas de neuroblastoma (que pueden diferenciarse a neurona) sobreexpresando POLG silvestre, POLG con una variante portadora de una mutación autosómica dominante o POLG con una variante previamente asociada a Parkinson. Con estos estudios, hemos comprobado que la sobreexpresión de la mutación patológica afecta a la replicación del DNA mitocondrial en la línea SH-SY5Y en cultivo, quedando disponible para comenzar los estudios de diferenciación neuronal. Por otro lado, se han caracterizado a nivel genético y molecular 3 líneas cíbridas para los haplogrupos mitocondriales: H, UK y J, derivadas de neuroblastoma sobreexpresando POLG silvestre, o la variante de POLG previamente asociada a Parkinson. Una vez caracterizadas se estudiará el efecto combinado que pueden tener variaciones genéticas mitocondriales y nucleares en la diferenciación a neurona dopaminérgica

Dinamización y movilización de procesos estructurales en familias con un diagnóstico de paladar hendido y labio fisurado

El propósito de este trabajo de investigación, pretendió desde una mirada sistémica socioconstruccionista, analizar cómo se movilizan, dinamizan la organización y el funcionamiento en seis familias con hijos que padecen paladar hendido y labio figurado, por medio de una entrevista semi estructurada. Esta investigación fué realizada por medio de la ayuda de una odontóloga quien trabaja con pacientes que padecen de la patología, la cual brindó la información de las familias con las cuales se llevaran a cabo las entrevistas. Dichas conversaciones fueron integradas en una matriz de análisis, la cual fué analizada a la luz de la teoría de la psicología sistémica. Dichas conversaciones implican una interacción constante entre las seis familias y las investigadoras, las cuales favorecen principios dialógicos para la comprensión de procesos de identificación de la estructura familia y su funcionamiento entre sus miembros.The purpose of this investigation is to analyze, from the systemic psychology, how six families mobilize their organization and operation, when there is a son or daughter with Cleft palate and/or cleft lip. This investigation took place with help from a dentist that works with this type of patients. We accessed to this information using a semi structured interview, and data we recollected was analyzed and organized with guidance of the systemic psychology.Psicólogo (a)Pregrad

Cambios temporales en los transportes y la distribución de las masas de agua a lo largo de la sección 20º W de CAIBOX (Atlántico NE)

24 páginas, 3 tablas, 7 figuras[EN] The CAIBOX cruise was conducted from 25 July to 14 August 2009. Three consecutive transects (zonal, meridional, and transverse) formed a closed box to the west of the Strait of Gibraltar. This study aimed to analyze the thermohaline properties, volume transports, and water mass distributions (percentages) along the meridional section (30–41.5º N, 20º W). We identified the main geostrophic current (Azores Current) and its associated volume transport and interannual changes. Data from previous cruises (AZORES I, A16N, CLIVAR, OACES, and CHAOS) with similar tracks were employed to compare with the CAIBOX meridional section. All but one (CHAOS) were summer cruises. We estimated a mean transport for the Azores Current at 20º W of 9.3 ± 2.6 Sv. There appears to be an inverse relation between the position of this current and its associated transport, with relatively high (low) transports when the current is located roughly south (north) of 35º N. Regarding water masses, an increase of 14.4% was found for Mediterranean Water compared with the 1993, 1998, and 2003 cruises; however, Labrador Sea Water decreased its contribution and southward spreading between 1998 and 2009[ES] Entre el 25 de julio y el 14 de agosto de 2009 se llevó a cabo la campaña CAIBOX, que constó de tres transectos consecutivos (zonal, occidental y transversal) conformando una caja cerrada al oeste del estrecho de Gibraltar. El objetivo principal del presente trabajo fue el estudio de las propiedades termohalinas, los transportes (en términos de volumen) y la distribución de las masas de agua (en porcentajes) a lo largo de la sección occidental (30–41.5º N, 20º W). Se identificó la corriente geostrófica principal (Corriente de las Azores), el transporte asociado a ella y sus cambios interanuales. Adicionalmente se consideraron los datos de cinco campañas anteriores (AZORES I, A16N, CLIVAR, OACES y CHAOS) con secciones similares a las de la campaña CAIBOX. Todas excepto una (CHAOS) fueron campañas estivales. El transporte medio para la Corriente de las Azores a 20º W se estimó en 9.3 ± 2.6 Sv. Parece existir cierta relación inversa entre la posición de dicha corriente y su transporte asociado, con transportes relativamente altos (bajos) cuando la corriente se sitúa al sur (norte) de 35º N. En cuanto a las masas de agua, se observa un incremento de 14.4% del Agua Mediterránea en comparación con las campañas de 1993, 1998 y 2003; sin embargo, el Agua de Labrador ha disminuido su contribución y su propagación hacia el sur entre 1998 y 2009.An important part of the data presented in this paper was obtained through the CAIBEX project: Shelf-ocean Exchanges in the Canaries-Iberia Large Marine Ecosystem (CTM2007-66408-C02/MAR), supported by the Spanish Ministry of Education and Science. The first author, LIC, was funded by a FPU predoctoral fellowship from the National Human Resources Formation Program, within the framework of the 2008–2011 National Scientific Research, Development and Technological Innovation Plan of the Spanish Ministry of Education. The fourth author, NVR, was supported by the Isabel Barreto Program (IN840E) from the Xunta de Galicia.Peer reviewe

Biotecnología, sostenibilidad y mejoramiento genético * ITANOA

En un contexto mundial de cambio climático y aumento poblacional preocupante, la ciencia y el desarrollo tecnológico deberán aportar la ayuda necesaria paramitigar la creciente necesidad de alimentos y energía renovable.Este escenario plantea grandes desafíos para la producción agrícola en las próximas décadas. La ONU estimó que para el año 2030 se necesitarán mil millonesde toneladas más de cereales por año (UNDP, 2015). Esta cifra es preocupante si se piensa en lograr estos incrementos mediante la utilización de las estrategias empleadas hasta el momento, es decir, expandir la superficie cultivada avanzandosobre ecosistemas naturales e intensificando el uso de fertilizantes y otros productos agroquímicos sintéticos, ya que conduciría indefectiblemente a profundizar el daño a la salud humana y ambiental.Fil: Pardo, Esteban Mariano. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto de Tecnología Agroindustrial del Noroeste Argentino. Provincia de Tucumán. Ministerio de Desarrollo Productivo. Estación Experimental Agroindustrial "Obispo Colombres" (p). Instituto de Tecnología Agroindustrial del Noroeste Argentino; ArgentinaFil: Rocha, C. M. L.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto de Tecnología Agroindustrial del Noroeste Argentino. Provincia de Tucumán. Ministerio de Desarrollo Productivo. Estación Experimental Agroindustrial "Obispo Colombres" (p). Instituto de Tecnología Agroindustrial del Noroeste Argentino; ArgentinaFil: Garcia, M.G. M.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto de Tecnología Agroindustrial del Noroeste Argentino. Provincia de Tucumán. Ministerio de Desarrollo Productivo. Estación Experimental Agroindustrial "Obispo Colombres" (p). Instituto de Tecnología Agroindustrial del Noroeste Argentino; ArgentinaFil: Pérez Borroto, Lucía Sandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto de Tecnología Agroindustrial del Noroeste Argentino. Provincia de Tucumán. Ministerio de Desarrollo Productivo. Estación Experimental Agroindustrial "Obispo Colombres" (p). Instituto de Tecnología Agroindustrial del Noroeste Argentino; ArgentinaFil: Toum, L. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto de Tecnología Agroindustrial del Noroeste Argentino. Provincia de Tucumán. Ministerio de Desarrollo Productivo. Estación Experimental Agroindustrial "Obispo Colombres" (p). Instituto de Tecnología Agroindustrial del Noroeste Argentino; ArgentinaFil: Filippone, María Paula. Universidad Nacional de Tucuman. Facultad de Agronomia y Zootecnia. Departamento de Ecología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto de Tecnología Agroindustrial del Noroeste Argentino. Provincia de Tucumán. Ministerio de Desarrollo Productivo. Estación Experimental Agroindustrial "Obispo Colombres" (p). Instituto de Tecnología Agroindustrial del Noroeste Argentino; ArgentinaFil: Castagnaro, Atilio Pedro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto de Tecnología Agroindustrial del Noroeste Argentino. Provincia de Tucumán. Ministerio de Desarrollo Productivo. Estación Experimental Agroindustrial "Obispo Colombres" (p). Instituto de Tecnología Agroindustrial del Noroeste Argentino; Argentin

Hitler y el nazismo

14 p.Adolf Hitler fue un militar dictador nacido en Braunau am Inn, Austria el 20 de abril de 1889, fue el cuarto de seis hermanos, hijos de Alois Hitler y Klara Polzl. Adolf primeramente se interesó por las bellas artes a lo cual su padre Alois no estuvo de acuerdo, de igual manera también mostró desde una temprana edad interés frente al nacionalismo alemán y el rechazo de la autoridad Austria-Hungría lo que le dio un nuevo sentido y motivación para su vida.Biografía Carrera política Ideología nazi Terror nazi Obras Conclusión Bibliografí

Is the association between health-related quality of life and fatigue mediated by depression in patients with multiple sclerosis? A Spanish cross-sectional study

OBJECTIVES: To determine the mediating effects of depression on health-related quality of life and fatigue in individuals with multiple sclerosis (MS). DESIGN: A cross-sectional study. SETTING: Tertiary urban hospital. PARTICIPANTS: One hundred and eight patients (54% women) with MS participated in this study. OUTCOME MEASURES: Demographic and clinical data (weight, height, medication and neurological impairment), fatigue (Fatigue Impact Scale), depression (Beck Depression Inventory-II) and health-related quality of life (Short-Form Health Survey 36) were collected. RESULTS: Fatigue was significantly associated with bodily pain, physical function, mental health and depression. Depression was associated with bodily pain and mental health. The path analysis found direct effects from physical function, bodily pain and depression to fatigue (all, P<0.01). The path model analysis revealed that depression exerted a mediator effect from bodily pain to fatigue (B=-0.04, P<0.01), and from mental health to fatigue (B=-0.16, P<0.01). The amount of fatigue explained by all predictors in the path model was 37%. CONCLUSIONS: This study found that depression mediates the relationship between some health-related quality of life domains and fatigue in people with MS. Future longitudinal studies focusing on proper management of depressive symptoms in individuals with MS will help determine the clinical implications of these finding

Discovery of Homobivalent Bitopic Ligands of the Cannabinoid CB2 Receptor**

Single chemical entities with potential to simultaneously interact with two binding sites are emerging strategies in medicinal chemistry. We have designed, synthesized and functionally characterized the first bitopic ligands for the CB2 receptor. These compounds selectively target CB2 versus CB1 receptors. Their binding mode was studied by molecular dynamic simulations and site-directed mutagenesis

Effects of Enteromyxum spp. (Myxozoa) infection in the regulation of intestinal E‐cadherin: Turbot against gilthead sea bream

This is the peer reviewed version of the following article: Ronza, P, Estensoro, I, Bermúdez, R, et al. Effects of Enteromyxum spp. (Myxozoa) infection in the regulation of intestinal E‐cadherin: Turbot against gilthead sea bream. J Fish Dis. 2020; 43: 337– 346, which has been published in final form at https://doi.org/10.1111/jfd.13130. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived VersionsEnteromyxoses are relevant diseases for turbot and gilthead sea bream aquaculture. The myxozoan parasites invade the intestinal mucosa, causing a cachectic syndrome associated with intestinal barrier alteration; nonetheless, their pathological impact is different. Turbot infected by Enteromyxum scophthalmi develop more severe intestinal lesions, reaching mortality rates of 100%, whereas in E. leei‐infected gilthead sea bream, the disease progresses slowly, and mortality rates are lower. The mechanisms underlying the different pathogenesis are still unclear. We studied the distribution and expression changes of E‐cadherin, a highly conserved protein of the adherens junctions, in the intestine of both species by immunohistochemistry and quantitative PCR, using the same immunohistochemical protocol and common primers. The regular immunostaining pattern observed in control fish turned into markedly irregular in parasitized turbot, showing an intense immunoreaction at the host–parasite interface. Nevertheless, E‐cadherin gene expression was not significantly modulated in this species. On the contrary, no evident changes in the protein distribution were noticed in gilthead sea bream, whereas a significant gene downregulation occurred in advanced infection. The results contribute to the understanding of the different host–parasite interactions in enteromyxoses. Host and parasite cells appear to establish diverse relationships in these species, which could underlie the different pathological pictureThis work has been funded by the Spanish Ministry of Economy and Competitiveness and the European Regional Development Fund (ERDF) through the projects AGL2015‐67039‐C3‐1‐R, AGL2015‐67039‐C3‐3‐R and AGL‐2013‐48560‐R and by the Horizon 2020 Framework Programme through ParaFishControl Project (634429). I.E. was contracted under APOSTD/2016/037 grant by the “Generalitat Valenciana” and G.P.‐C. under the “Juan de la Cierva” programme, granted by the Spanish Ministry of Science and Innovation (JCI‐2011‐09438)S

Palaeolithic – Epipalaeolithic Seapeople of the Southern Iberian coast (Spain): an overview

The significance of coastal areas to human survival and expansion on the planet is undeniable. Their ecological diversity and their use as communication routes are some of their most distinctive qualities. However, the evidence of exploitation of these resources has had an uneven preservation, which is limited to certain regions and more recent events, mainly sites with deposits from the Upper Pleistocene and Holocene. This paper analyses the data available on the use of marine resources between MIS 6 and MIS 1 (c. 150 – 9 ka BP) in Southern Iberia, one of the first regions in Europe where marine faunal remains were discovered, in archaeological deposits from Middle and Upper Palaeolithic. Therefore their presence here has not been a criterion of separation between Neanderthals and Modern humans, but it may be relevant to analyze changes in the use of small preys or assess the economic diversification in regions where this came at an early date. One of the aims of this study was to evaluate the diachronic trends of the different palaeobiological marine remains recovered from coastal and inland archaeological sites. This preliminary extract indicates that the analysis of marine resource exploitation cannot be classed as a mere listing of palaeobiological remains. This information may be relevant in the initial stages, but it is insufficient in the evaluation of techno-economic and sociocultural transformations that can be linked to the use of marine resources. The distribution of palaeobiological marine remains differs over time and also according to the location of the sites with respect to the changing coastline throughout the period analysed. The known sites that preserve evidence of the use of marine resources as a food source are located mainly on the present coastline, or in a range of less than 10 km. Invertebrate remains have been identified in most, whereas fish, bird and mammal bones only in certain sites. Molluscs used as ornaments or pendants and containers are more widely distributed than other species used for food. Because these data must be contextualized, bone and stone tools linked to the exploitation of the marine environment have been added to the palaeobiological information, drawing inferences based on the analogy between both ethnologically and archaeologically documented tools. Symbolic expressions have also been studied, given the significant number of painted and engraved marine fauna depictions, specifically pisciforms and mammals, found in southern Iberia. Lastly, available molecular data has also been evaluated, from the results of isotope analysis on human remains. This combination of palaeobiological, techno-economic, graphic-symbolic and molecular data, allows a first assessment of the use of marine resources in the region

Health-related quality of life in well-differentiated metastatic gastroenteropancreatic neuroendocrine tumors

Spanish Neuroendocrine Tumor Group (GETNE)© 2015, Springer Science+Business Media New York. Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare neoplasms capable of producing hormones. The development of new treatments has improved progression-free survival, albeit with increased toxicity. Health-related quality of life (HRQoL) has become an important endpoint in clinical research to evaluate patients’ well-being in such a contradictory scenario. In this review, we examine key reported outcomes across clinical studies exploring HRQoL in patients with GEP-NETs. We have conducted a review of the literature using PubMed, The Cochrane Library, EMBASE, and Google Scholar. Selection criteria for articles were (1) publication in English between 1995 and 2014, (2) patients with GEP-NET, and (3) analysis of HRQoL, including mental health and psychological symptoms. Forty-nine studies met the inclusion criteria (31 clinical trials, 14 observational studies, and 4 developments of NET-specific HRQoL instruments). The scope and nature of the literature was diverse with 27 instruments used to measure aspects of HRQoL. EORTC QLQ-C30 was the most frequently used, in 38 of the 49 studies. Standardized measures revealed that in spite of generally good HRQoL, GEP-NET patients have specific psychological and physical complaints. The clinical benefit of somatostatin analogs and sunitinib has been clearly supported by HRQoL assessment. Improvement in HRQoL scores or symptom relief over time was also reported in 14 trials of peptide receptor radionuclide therapy, however the absence of randomized studies obviate definitive conclusions. We have also identified several unanswered questions that should be addressed in further research concerning chemotherapy, everolimus, surgery, local ablative therapies, and chemoembolization. Future research should incorporate GEP-NET-specific HRQoL instruments into phase III trials. This review may help both clinicians and researchers to select the most appropriate tools to assess changes in HRQoL in this population.This project was funded in part by a restricted educational grant from Novartis Spain and by support from the Spanish Neuroendocrine Tumor Group (GETNE).Peer Reviewe