Disrupted in schizophrenia 1 (DISC1): regulation of the neuropeptide VGF and role in neurodevelopment and synapses

Since Disrupted in schizophrenia 1 (Disc1) was discovered, it has become one of the most convincing risk genes for major mental illness. Disc1 was first identified in a large Scottish family in which a genomic translocation affecting this gene cosegregated with major psychiatric diseases including schizophrenia, major depression and bipolar disorder. The protein encoded (DISC1) is highly expressed in the brain and, to date, no evidence of enzymatic activity has been reported. However, DISC1 binds more than 200 different proteins and acts as a molecular scaffold regulating the activity of such proteins. Thus, through these interactions, DISC1 participates in several processes in the brain such as neuronal proliferation, migration and differentiation as well as neurite outgrowth and synapse regulation. In order to gain new insight into the functions of DISC1, knock-down of the protein was performed in primary cortex and hippocampus mouse neurons as well as in the human neuroblastoma SH-SY5Y cell line by means of infection with small hairpin RNA (shRNA)-carrying lentivirus. In the present study DISC1 knock-down was found to lead to an important decrease in the levels of the neuropeptide VGF (non-acronymic) in SH-SY5Y as well as in primary cortical and hippocampal mouse neurons. Of note, VGF displays antidepressant properties and has been also shown to be implicated in different neuropsychiatric disorders including depression, bipolar disorder and schizophrenia. The fall of VGF levels produced by DISC1 knock-down seems to be mediated by a drop in the activity of the PI3K/AKT/CREB signaling as indicated by decreased levels of the active forms of AKT and CREB. Additionally, a decline in the levels of Grb2, an essential protein for PI3K activation and the subsequent signaling route, was observed in SH-SY5Y cells. In addition, knock-down of DISC1 was found to result in changes in the quantity and phosphorylation of GSK3β in primary mouse neurons suggesting the deregulation of the activity of the kinase. Furthermore, by means of a proteomic approach, the knock-down of DISC1 was observed to cause the differential regulation of a number of proteins in primary mouse neurons. Twelve of the proteins affected by the lack of DISC1 are involved in neurodevelopment and twelve participate in different aspects of the synapses. Of note, seven of these proteins share functions in both processes. Some of these proteins are known DISC1 binding partners; however, this is the first time that their expression is described to be dependent on DISC1. Supporting a role for DISC1 in neurodevelopment, its knock-down also produced deficits in the neurite outgrowth in SH-SY5Y cells treated with retinoic acid to induce their differentiation. The DISC1-VGF connection showed in the present study might be important for the development of new therapies for the treatment of mental diseases. In addition, the results show a new mechanism by which DISC1 regulates the activity of several proteins in neurons through the regulation of their levels

La investigación sobre libros de texto y materiales curriculares

Este trabalho apresenta uma classificação das diferentes perspetivas e linhas de pesquisa que foram analisadas e desenvolvidas nos últimos anos sobre materiais didáticos. Essas perspetivas foram as seguintes: (i) papel e influência dos manuais escolares e dos materiais curriculares nas práticas de aula; (ii) discurso ideológico subjacente aos materiais; (iii) análise dos aspetos formais nos manuuais escolares e noutros materiais curriculares; (iv) impacto das políticas e processos de reforma educacional sobre as características desses materiais; (v) função e estudo desses materiais nas diferentes áreas do currículo e nas didáticas específicas; (vi) análise do manual escolar e de outros materiais como discurso curricular e de profissionalização docente; (vii) processos de comercialização dos manuais escolares e programas de gratuidade; (viii) diretrizes para avaliação e análise de manuais escolares; e (ix) investigação sobre a elaboração de materiais pedagógicos alternativos. Neste estudo, apresentamos algumas investigações que nos parecem interessantes vir a desenvolver sobre manuais escolaires nos próximos anosThis paper presents a classification of the different perspectives and research lines analyzed and developed in recent years regarding textbooks. The perspectives considered were: (i) The role and influence in the classroom practices of textbooks and curriculum materials; (ii) Underlying ideological speech in educational materials; (iii) Analysis of the formal aspects in textbooks and other instructional materials; (iv) The impact of policies and educational reform processes on the characteristics of materials; (v) The function and the study of materials in different areas of the curriculum and specific didactics; (vi) Analysis of textbook and other curricular materials speech and teacher professionalism; (vii) Processes marketing of textbooks and free programs; (viii) Guidelines for evaluation and analysis of texts; (ix) Research on the development of alternative materials. The paper concludes by mentioning some research that seems interesting to develop in relation to textbooks in the coming yearsCet article présente une classification des différentes perspectives et axes de recherche analysés et développés au cours des dernières années concernant les manuels scolaires. Les perspectives considérés ont été les suivantes: (i) Le rôle et l’influence des manuels et de matériels pédagogiques dans les pratiques de classe; (ii) Discours idéologique soustendu dans le matériel pédagogique; (iii) L’analyse des aspects formels dans les manuels scolaires et autres matériels didactiques; (iv) L’impact des politiques et des processus de réforme de l’éducation sur les caractéristiques des matériaux; (v) La fonction et l’étude des matériaux dans différents domaines du programme scolaire et didactique spécifiques; (vi) Manuel d’analyse et d’autres matières scolaires telles que la parole et le professionnalisme des enseignants; (vii) Processus de commercialisation des manuels scolaires et les programmes libres; (viii) Lignes directrices pour l’évaluation et l’analyse des textes; (ix) La recherche sur le développement de matériaux alternatifs. Le document conclut en mentionnant quelques recherches qui semblent intéressantes à développer par rapport aux manuels scolaires dans les années à venirEste artículo presenta una clasificación de las distintas perspectivas y líneas de investigación que se analizaron y desarrollaron en los últimos años en relación con los libros de texto. Las líneas de investigación consideradas fueron las siguientes: (i) El papel y la influencia en las prácticas de aula de los libros de texto y materiales curriculares; (ii) Discurso ideológico subyacente en los materiales educativos; (iii) Análisis de los aspectos formales en los libros de texto y otros materiales curriculares; (iv) La repercusión de las políticas y los procesos de Reforma Educativa sobre las características de los materiales; (v) La función y el estudio de los materiales en las diferentes áreas del curriculum y en las didácticas específicas; (vi) Análisis del libro de texto y otros materiales como discurso curricular y de profesionalidad docente; (vii) Procesos de comercialización de los libros de texto y programas de gratuidad; (viii) Guías de evaluación y análisis de textos; e (ix) Investigaciones sobre la elaboración de materiales alternativos. El artículo concluye mencionando algunas líneas de investigación que parece interesante desarrollar en relación con los libros de texto en los próximos añosS

Literature review on research related to textbooks and learning materials in physical education in the Spanish context

Este trabajo muestra una revisión de los trabajos de investigación que se han realizado en los últimos años en el contexto español en relación con los libros de texto, materiales didácticos y el ámbito de la Educación Física. La información utilizada está basada en la revisión de estudios que han sido publicados en diversas bases de datos tales como: ISOC, DIALNET, GOOGLE SCHOLAR, TESEO, REDALYC entre otras. De la misma manera se han considerado los congresos, jornadas y actividades que recientemente han tenido lugar tanto a nivel nacional como internacional y que han estado dirigidas especialmente al ámbito de la Educación Física y los materiales didácticos. Inicialmente presentaremos algunas reflexiones iniciales sobre la necesidad de realizar la revisión y posteriormente mostraremos una síntesis de los principales trabajos encontrados y su clasificaciónHere we carry out a review of recent research in the Spanish context regarding textbooks, didactic materials and the field of Physical Education. Information is drawn from studies available in various databases such as ISOC, DIALNET, GOOGLE SCHOLAR, TESEO, and REDALYC. Special attention has also been given to congresses, seminars and activities that have recently been held nationally and internationally and which have focused on the fields of Physical Education and teaching materials. We will begin with some initial comments on the need to carry out the present review and we will go on to summarize and classify the main studies foundS

Elaboración de blogs como herramienta virtual de aprendizaje y trabajo en equipo

Este proyecto de innovación se enmarca dentro de las actividades académicas no presenciales. Se trata de la elaboración de blogs como herramienta virtual de aprendizaje. Los blogs son un recurso de aprendizaje individual o grupal, de gran versatilidad y dinamización del aula. Además, promueve el desarrollo de competencias generales, específicas y transversales que los alumnos deben adquirir durante su formación. Creemos que su aplicación es especialmente interesante en asignaturas como “Bases Celulares de la Genética Humana” impartida en primero de Medicina, donde los alumnos se encuentran con una dificultad añadida a la complejidad de sus fundamentos: unos conceptos complejos con una terminología muy específica para asimilarlos. Los futuros médicos deberán ser capaces, de explicar con un lenguaje sencillo y comprensible a los pacientes la implicación de la genética en las patologías. Consideramos que el uso de blogs está especialmente indicado en este caso para facilitar la adquisición de esta competencia específica, además de apoyar el aprendizaje de parte de los contenidos de la asignatura y promover el trabajo en equipo. Esta herramienta aporta a los alumnos las competencias necesarias para su formación integral como profesional de la salud promoviendo el intercambio colaborativo. Es además, un recurso que puede ser utilizado tanto para la evaluación continua, por parte del profesor durante y a la finalización del diseño del blog, así como para la coevaluación entre los alumnos. Por tanto, esta propuesta facilita el aprendizaje creando espacios para ello. En definitiva, crea oportunidades de aprendizaje

Flexure Strength and Fracture Propagation in Zirconia Ceramic Composites with Exfoliated Graphene Nanoplatelets

In this work, the flexure strength and fracture propagation mechanisms in yttria tetragonal zirconia (3YTZP) dense composites with 1 and 5 vol.% exfoliated graphene nanoplatelets (e-GNP) were assessed. The composite powders were processed by dry planetary ball milling to exfoliate the as-received GNP, and then densified by spark plasma sintering (SPS). The hardness and Young’s modulus were measured by Vickers indentation and the impulse-echo technique, respectively. Flexural strength and modulus were estimated by four-point bending tests. Finally, cracks originated by Vickers indentations were analyzed by scanning electron microscopy (SEM). The Raman spectra and SEM observations showed a reduction in the number of graphene layers and most remarkably in the lateral size of the e-GNP, achieving a very homogeneous distribution in the ceramic matrix. The hardness, elastic modulus, and flexural strength of the 3YTZP matrix did not vary significantly with the addition of 1 vol.% e-GNP, but they decreased when the content increased to 5 vol.%. The addition of e-GNP to 3YTZP increased its reliability under bending, and the small lateral size of the e-GNP produced isotropic fracture propagation. However, the energy dissipation mechanisms conventionally attributed to the larger GNP such as fracture deflection or blocking were limited.Ministerio de Economía y Competitividad MAT 2015-67889-PMinisterio de Ciencia, Innovación y Universidades PGC 2018–101377–B-10

Evaluation of Prescribed Fires from Unmanned Aerial Vehicles (UAVs) Imagery and Machine Learning Algorithms

Producción CientíficaPrescribed fires have been applied in many countries as a useful management tool to prevent large forest fires. Knowledge on burn severity is of great interest for predicting post-fire evolution in such burned areas and, therefore, for evaluating the efficacy of this type of action. In this research work, the severity of two prescribed fires that occurred in “La Sierra de Uría” (Asturias, Spain) in October 2017, was evaluated. An Unmanned Aerial Vehicle (UAV) with a Parrot SEQUOIA multispectral camera on board was used to obtain post-fire surface reflectance images on the green (550 nm), red (660 nm), red edge (735 nm), and near-infrared (790 nm) bands at high spatial resolution (GSD 20 cm). Additionally, 153 field plots were established to estimate soil and vegetation burn severity. Severity patterns were explored using Probabilistic Neural Networks algorithms (PNN) based on field data and UAV image-derived products. PNN classified 84.3% of vegetation and 77.8% of soil burn severity levels (overall accuracy) correctly. Future research needs to be carried out to validate the efficacy of this type of action in other ecosystems under different climatic conditions and fire regimes.Ministerio de Economía, Industria y Competitividad - Fondo Europeo de Desarrollo Regional (project AGL2017-86075-C2-1-R)Junta de Castilla y León (project LE001P17

Proteomic Studies Reveal Disrupted in Schizophrenia 1 as a Player in Both Neurodevelopment and Synaptic Function

A balanced chromosomal translocation disrupting DISC1 (Disrupted in Schizophrenia 1) gene has been linked to psychiatric diseases, such as major depression, bipolar disorder and schizophrenia. Since the discovery of this translocation, many studies have focused on understating the role of the truncated isoform of DISC1, hypothesizing that the gain of function of this protein could be behind the neurobiology of mental conditions, but not so many studies have focused in the mechanisms impaired due to its loss of function. For that reason, we performed an analysis on the cellular proteome of primary neurons in which DISC1 was knocked down with the goal of identifying relevant pathways directly affected by DISC1 loss of function. Using an unbiased proteomic approach, we found that the expression of 31 proteins related to neurodevelopment (e.g., CRMP-2, stathmin) and synaptic function (e.g., MUNC-18, NCS-1) is altered by DISC1 in primary mouse neurons. Hence, this study reinforces the idea that DISC1 is a unifying regulator of both neurodevelopment and synaptic function, thereby providing a link between these two key anatomical and cellular circuitries.This research was funded by ERANET-NEURON, grant DISCover (National funding institution grants: ISCIII PI09/2688 and BMBF 01EW1003, respectively, to J.R.R. and C.K.), and grants from the DFG (Ko1679/3-1), NARSAD 2013 Independent Investigator Award #20350 and EU-FP MC-ITN "IN-SENS" #607616) (C.K.); The Spanish Ministry of Science and Innovation (SAF2011-30494 and BFU2017-86692-P, partially funded by European Union regional funds (FRDER)); the Departments of Industry, Tourism and Trade (Etortek) and Innovation Technology of the Government of the Autonomous Community of the Basque Country (R.M.K. and I.G-E.); and the Spanish Ministry of Economy and Competitiveness (SAF2013-45014-R, A.G., SAF2011-30494 (R.M.K. and I.G-E.))S

Predicting pharmaceutical inkjet printing outcomes using machine learning

[Abstract]: Inkjet printing has been extensively explored in recent years to produce personalised medicines due to its low cost and versatility. Pharmaceutical applications have ranged from orodispersible films to complex polydrug implants. However, the multi-factorial nature of the inkjet printing process makes formulation (e.g., composition, surface tension, and viscosity) and printing parameter optimization (e.g., nozzle diameter, peak voltage, and drop spacing) an empirical and time-consuming endeavour. Instead, given the wealth of publicly available data on pharmaceutical inkjet printing, there is potential for a predictive model for inkjet printing outcomes to be developed. In this study, machine learning (ML) models (random forest, multilayer perceptron, and support vector machine) to predict printability and drug dose were developed using a dataset of 687 formulations, consolidated from in-house and literature-mined data on inkjet-printed formulations. The optimized ML models predicted the printability of formulations with an accuracy of 97.22%, and predicted the quality of the prints with an accuracy of 97.14%. This study demonstrates that ML models can feasibly provide predictive insights to inkjet printing outcomes prior to formulation preparation, affording resource- and time-savings.The research was partially supported by MCIN (PID 2020-113881RB-I00/AEI/10.13039/501100011033), Spain, Xunta de Galicia (ED431C 2020/17), and FEDER.L.R.P. acknowledges the predoctoral fellowship provided by the Ministerio de Universidades (Formación de Profesorado Universitario (FPU 2020). I.S.V. acknowledges Consellería de Cultura, Educación e Universidade for her Postdoctoral Fellowship (Xunta de Galicia, Spain; ED481B-2021-019). L.R.P. acknowledges the predoctoral fellowship provided by the Ministerio de Universidades (Formación de Profesorado Universitario (FPU 2020) .Xunta de Galicia; ED431C 2020/17Xunta de Galicia; ED481B-2021-01

Concordance among methods of nutritional assessment in patients included on the waiting list for liver transplantation

[Abstract] Background: The aim of the present study was to determine the extent of malnutrition in patients waiting for a liver transplant. The agreement among the methods of nutritional assessment and their diagnostic validity were evaluated. Methods: Patients on the waiting list for liver transplantation (n = 110) were studied. The variables were: body mass index, analytical parameters, liver disease etiology, and complications. Liver dysfunction was evaluated using the Child-Pugh Scale. Nutritional state was studied using the Controlling Nutritional Status (CONUT), the Spanish Society of Parenteral and Enteral Nutrition (SENPE) criteria, the Nutritional Risk Index (NRI), the Prognostic Nutritional Index (PNI-O), and the Subjective Global Assessment (SGA). Agreement was determined using the Kappa index. Area under receiver operator characteristic curves (AUCs), the Youden index (J), and likelihood ratios were computed. Results: Malnutrition varied depending on the method of evaluation. The highest value was detected using the CONUT (90.9%) and the lowest using the SGA (50.9%). The pairwise agreement among the methods ranged from K = 0.041 to K = 0.826, with an overall agreement of each criteria with the remaining methods between K = 0.093 and K = 0.364. PNI-O was the method with the highest overall agreement. Taking this level of agreement into account, we chose the PNI-O as a benchmark method of comparison. The highest positive likelihood ratio for the diagnosis of malnutrition was obtained from the Nutritional Risk Index (13.56). Conclusions: Malnutrition prevalence is high and prevalence estimates vary according the method used, with low concordance among methods. PNI-O and NRI are the most consistent methods to identify malnutrition in these patients.Instituto de Salud Carlos III; PI11/012

Bioactives Overproduction through Operational Strategies in the Ichthyotoxic Microalga Heterosigma akashiwo Culture

The red tide-forming microalga Heterosigma akashiwo has been associated with massive events of fish deaths, both wild and cultured. Culture conditions are responsible for the synthesis or accumulation of some metabolites with different interesting bioactivities. H. akashiwo LC269919 strain was grown in a 10 L bubble column photobioreactor artificially illuminated with multi-coloured LED lights. Growth and production of exopolysaccharides, polyunsaturated fatty acids (PUFAs), and carotenoids were evaluated under different culture modes (batch, fed-batch, semicontinuous, and continuous) at two irradiance levels (300 and 700 µE·s−1·m−2). Continuous mode at the dilution rate of 0.2·day−1 and 700 µE·s−1·m−2 provided the highest production of biomass, PUFAs (132.6 and 2.3 mg·L−1·day−1), and maximum fucoxanthin productivity (0.16 mg·L−1·day−1). The fed-batch mode accumulated exopolysaccharides in a concentration (1.02 g·L−1) 10-fold over the batch mode. An extraction process based on a sequential gradient partition with water and four water-immiscible organic solvents allowed the isolation of bioactive fucoxanthin from methanolic extracts of H. akashiwo. Metabolites present in H. akashiwo, fucoxanthin and polar lipids (i.e., eicosapentaenoic acid (EPA)), or probably such as phytosterol (β-Sitosterol) from other microalgae, were responsible for the antitumor activity obtained.This research was funded by the General Secretariat of Universities, Research and Technology of the Andalusian Government (grant: P18-RT-2477) and the State Research Agency (grants PID2019-109476RB-C22) of the Spanish Ministry of Science, Innovation and Universities