Estereotipos de género en el dibujo infantil: análisis y estrategias de intervención

El presente Trabajo Fin de Grado expone un estudio sobre los estereotipos de género en el dibujo infantil. Se presenta una base teórica que plantea la importancia de una educación en valores basada en la igualdad de género. Se explica el origen y pervivencia de este tipo de estereotipos tan arraigados en la sociedad que permiten que ciertas desigualdades de género aún perduren. Explicaremos por qué la etapa de infantil es especialmente susceptible a los estereotipos de género. Nos basaremos en el dibujo como medio de análisis y medida de la expresión de estereotipos de género clave que detectamos, en concreto realizaremos un estudio en un aula de primero de Educación Infantil. Reflexionamos sobre las posibles consecuencias de continuar sin tratar este tema desde la escuela y plantearemos propuestas y estrategias de intervención que nos permitan comprobar si los estereotipos de género son algo que pueda “desaprenderse” o superarse una vez adquiridos.Grado en Educación Infanti

SMN Requirement for Synaptic Vesicle, Active Zone and Microtubule Postnatal Organization in Motor Nerve Terminals

Low levels of the Survival Motor Neuron (SMN) protein produce Spinal Muscular Atrophy (SMA), a severe monogenetic disease in infants characterized by muscle weakness and impaired synaptic transmission. We report here severe structural and functional alterations in the organization of the organelles and the cytoskeleton of motor nerve terminals in a mouse model of SMA. The decrease in SMN levels resulted in the clustering of synaptic vesicles (SVs) and Active Zones (AZs), reduction in the size of the readily releasable pool (RRP), and the recycling pool (RP) of synaptic vesicles, a decrease in active mitochondria and limiting of neurofilament and microtubule maturation. We propose that SMN is essential for the normal postnatal maturation of motor nerve terminals and that SMN deficiency disrupts the presynaptic organization leading to neurodegeneration

Indice estatal de libertad de expresión 2019. Nuevo León [Introducción]

En México hablar de democracia, implica la referencia obligada de las relaciones Estado -sociedad y sus principios de vinculación constitucional. Estas relaciones no se han caracterizado por ser libres, con principios de igualdad y equidad, que son los parámetros básicos para medir el grado real de democratización. Exponer los procesos de transición que han existido en México, implica hacer referencias a las diversas luchas que se han emprendido en diversos frentes para alcanzar estos principios básicos. Una de ellas, particularmente es el ejercicio pleno del derecho a la libertad de expresión, garantizado en los artículos sexto y séptimo constitucionales. De forma resumida, señalamos que el sentido clásico de la libertad de expresión estriba en primer término en incentivar el desarrollo tanto personal como social. En segundo término, se hace referencia a los incentivos que se generan a partir del cumplimiento de este derecho fundamental, a la deliberación pública democrática (Madrazo, 2011:18-19). Evidentemente, al contrastar esta teorización con los casos empíricos y medir el grado de libertad de expresión, podemos encontrar hondas diferencias si revisamos a las entidades federativas. El estado de Nuevo León, a pesar de que ha experimentado procesos de alternancia política, esto no ha significado necesariamente un avance sustantivo en la democracia (Medellín, 2011) y en un eficaz Estado de derecho, que es una de las arenas indispensables de la consolidación del modelo democrático (Linz y Stepan, 1996). En mediciones recientes, Nuevo León está clasificado con un grado de impunidad muy alto [ocupando el lugar 17], mostrando un atraso importante en la procuración de justicia en el estado (Le Clercq y Rodríguez, 2018:40). En Nuevo León, al igual que en otros estados, se han incrementado los niveles de criminalidad y de presencia activa de carteles de narcotráfico. De acuerdo a un estudio de México Peace Index, hubo un aumento de la violencia en 87% en los años del 2003 al 2012, llegando al lugar 30 de 32 con los peores promedios de deterioro (Mexico Peace Index 2013: 11)

Notch Signaling Pathway Is Activated in Motoneurons of Spinal Muscular Atrophy

Spinal muscular atrophy (SMA) is a neurodegenerative disease produced by low levels of Survival Motor Neuron (SMN) protein that affects alpha motoneurons in the spinal cord. Notch signaling is a cell-cell communication system well known as a master regulator of neural development, but also with important roles in the adult central nervous system. Aberrant Notch function is associated with several developmental neurological disorders; however, the potential implication of the Notch pathway in SMA pathogenesis has not been studied yet. We report here that SMN deficiency, induced in the astroglioma cell line U87MG after lentiviral transduction with a shSMN construct, was associated with an increase in the expression of the main components of Notch signaling pathway, namely its ligands, Jagged1 and Delta1, the Notch receptor and its active intracellular form (NICD). In the SMNΔ7 mouse model of SMA we also found increased astrocyte processes positive for Jagged1 and Delta1 in intimate contact with lumbar spinal cord motoneurons. In these motoneurons an increased Notch signaling was found, as denoted by increased NICD levels and reduced expression of the proneural gene neurogenin 3, whose transcription is negatively regulated by Notch. Together, these findings may be relevant to understand some pathologic attributes of SMA motoneurons.This work was supported by grants from Fundación Genoma España, GENAME to JL, LT and RMS, and from Instituto de Salud Carlos III-Fondo de Investigaciones Sanitarias (PI11/01047) to RMS. AG holds a postdoctoral contract from Genoma España. VC-M and AC-R have been supported by a predoctoral fellowship from “Govern de les Illes Balears, Conselleria d’Educació, Cultura i Universitats” under a program of joint financing with the European Social Fund

Design of an intelligent decision support system applied to the diagnosis of obstructive sleep apnea

Obstructive sleep apnea (OSA), characterized by recurrent episodes of partial or total obstruction of the upper airway during sleep, is currently one of the respiratory pathologies with the highest incidence worldwide. This situation has led to an increase in the demand for medical appointments and specific diagnostic studies, resulting in long waiting lists, with all the health consequences that this entails for the affected patients. In this context, this paper proposes the design and development of a novel intelligent decision support system applied to the diagnosis of OSA, aiming to identify patients suspected of suffering from the pathology. For this purpose, two sets of heterogeneous information are considered. The first one includes objective data related to the patient’s health profile, with information usually available in electronic health records (anthropometric information, habits, diagnosed conditions and prescribed treatments). The second type includes subjective data related to the specific OSA symptomatology reported by the patient in a specific interview. For the processing of this information, a machine-learning classification algorithm and a set of fuzzy expert systems arranged in cascade are used, obtaining, as a result, two indicators related to the risk of suffering from the disease. Subsequently, by interpreting both risk indicators, it will be possible to determine the severity of the patients’ condition and to generate alerts. For the initial tests, a software artifact was built using a dataset with 4400 patients from the Álvaro Cunqueiro Hospital (Vigo, Galicia, Spain). The preliminary results obtained are promising and demonstrate the potential usefulness of this type of tool in the diagnosis of OSA.Xunta de Galicia | Ref. ED481A-2020/03

microRNA Expression and Its Association With Disability and Brain Atrophy in Multiple Sclerosis Patients Treated With Glatiramer Acetate.

Background: MicroRNAs are small non-coding RNA that regulate gene expression at a post-transcriptional level affecting several cellular processes including inflammation, neurodegeneration and remyelination. Different patterns of miRNAs expression have been demonstrated in multiple sclerosis compared to controls, as well as in different courses of the disease. For these reason they have been postulated as promising biomarkers candidates in multiple sclerosis. Objective: To correlate serum microRNAs profile expression with disability, cognitive functioning and brain volume in patients with remitting-relapsing multiple sclerosis. Methods: Cross-sectional study in relapsing-remitting multiple sclerosis patients treated with glatiramer acetate. Disability was measured with Expanded Disability Status Scale (EDSS) and cognitive function was studied with Symbol Digit Modalities Test (SDMT). Brain volume was analyzed with automatic software NeuroQuant® . Results: We found an association between miR.146a.5p (rs:0.434, p=0.03) and miR.9.5p (rs:0.516, p=0.028) with EDSS; and miR-146a.5p (rs:-0.476, p=0.016) and miR-126.3p (rs:-0.528, p=0.007) with SDMT. Regarding to the brain volume, miR.9.5p correlated with thalamus (rs:-0.545, p=0.036); miR.200c.3p with pallidum (rs:-0.68, p=0.002) and cerebellum (rs:-0.472, p=0.048); miR-138.5p with amygdala (rs:0.73, p=0.016) and pallidum (rs:0.64, p=0.048); and miR-223.3p with caudate (rs:0.46, p=0.04). Conclusions: These data support the hypothesis of microRNA as potential biomarkers in this disease. More studies are needed to validate these results and to better understand the role of microRNAs in the pathogenesis, monitoring and therapeutic response of multiple sclerosis.post-print1410 K

Regulation of BDNF Release by ARMS/Kidins220 through Modulation of Synaptotagmin-IV Levels

BDNF is a growth factor with important roles in the nervous system in both physiological and pathological conditions, but the mechanisms controlling its secretion are not completely understood. Here, we show that ARMS/Kidins220 negatively regulates BDNF secretion in neurons from the CNS and PNS. Downregulation of the ARMS/Kidins220 protein in the adult mouse brain increases regulated BDNF secretion, leading to its accumulation in the striatum. Interestingly, two mouse models of Huntington's disease (HD) showed increased levels of ARMS/Kidins220 in the hippocampus and regulated BDNF secretion deficits. Importantly, reduction of ARMS/Kidins220 in hippocampal slices from HD mice reversed the impaired regulated BDNF release. Moreover, there are increased levels of ARMS/Kidins220 in the hippocampus and PFC of patients with HD. ARMS/Kidins220 regulates Synaptotagmin-IV levels, which has been previously observed to modulate BDNF secretion. These data indicate that ARMS/Kidins220 controls the regulated secretion of BDNF and might play a crucial role in the pathogenesis of HD.SIGNIFICANCE STATEMENT BDNF is an important growth factor that plays a fundamental role in the correct functioning of the CNS. The secretion of BDNF must be properly controlled to exert its functions, but the proteins regulating its release are not completely known. Using neuronal cultures and a new conditional mouse to modulate ARMS/Kidins220 protein, we report that ARMS/Kidins220 negatively regulates BDNF secretion. Moreover, ARMS/Kidins220 is overexpressed in two mouse models of Huntington's disease (HD), causing an impaired regulation of BDNF secretion. Furthermore, ARMS/Kidins220 levels are increased in brain samples from HD patients. Future studies should address whether ARMS/Kidins220 has any function on the pathophysiology of HD

Neurocalcin Delta Knockout Impairs Adult Neurogenesis Whereas Half Reduction Is Not Pathological

Neurocalcin delta (NCALD) is a brain-enriched neuronal calcium sensor and its reduction acts protective against spinal muscular atrophy (SMA). However, the physiological function of NCALD and implications of NCALD reduction are still elusive. Here, we analyzed the ubiquitous Ncald knockout in homozygous (NcaldKO/KO) and heterozygous (NcaldKO/WT) mice to unravel the physiological role of NCALD in the brain and to study whether 50% NCALD reduction is a safe option for SMA therapy. We found that NcaldKO/KO but not NcaldKO/WT mice exhibit significant changes in the hippocampal morphology, likely due to impaired generation and migration of newborn neurons in the dentate gyrus (DG). To understand the mechanism behind, we studied the NCALD interactome and identified mitogen-activated protein kinase kinase kinase 10 (MAP3K10) as a novel NCALD interacting partner. MAP3K10 is an upstream activating kinase of c-Jun N-terminal kinase (JNK), which regulates adult neurogenesis. Strikingly, the JNK activation was significantly upregulated in the NcaldKO/KO brains. Contrary, neither adult neurogenesis nor JNK activation were altered by heterozygous Ncald deletion. Taken together, our study identifies a novel link between NCALD and adult neurogenesis in the hippocampus, possibly via a MAP3K10-JNK pathway and emphasizes the safety of using NCALD reduction as a therapeutic option for SMA

Plastin 3 is upregulated in iPSC-derived motoneurons from asymptomatic SMN1-deleted individuals

Spinal muscular atrophy (SMA) is a devastating motoneuron (MN) disorder caused by homozygous loss of SMN1. Rarely, SMN1-deleted individuals are fully asymptomatic despite carrying identical SMN2 copies as their SMA III-affected siblings suggesting protection by genetic modifiers other than SMN2. High plastin 3 (PLS3) expression has previously been found in lymphoblastoid cells but not in fibroblasts of asymptomatic compared to symptomatic siblings. To find out whether PLS3 is also upregulated in MNs of asymptomatic individuals and thus a convincing SMA protective modifier, we generated induced pluripotent stem cells (iPSCs) from fibroblasts of three asymptomatic and three SMA III-affected siblings from two families and compared these to iPSCs from a SMA I patient and control individuals. MNs were differentiated from iPSC-derived small molecule neural precursor cells (smNPCs). All four genotype classes showed similar capacity to differentiate into MNs at day 8. However, SMA I-derived MN survival was significantly decreased while SMA III- and asymptomatic-derived MN survival was moderately reduced compared to controls at day 27. SMN expression levels and concomitant gem numbers broadly matched SMN2 copy number distribution; SMA I presented the lowest levels, whereas SMA III and asymptomatic showed similar levels. In contrast, PLS3 was significantly upregulated in mixed MN cultures from asymptomatic individuals pinpointing a tissue-specific regulation. Evidence for strong PLS3 accumulation in shaft and rim of growth cones in MN cultures from asymptomatic individuals implies an important role in neuromuscular synapse formation and maintenance. These findings provide strong evidence that PLS3 is a genuine SMA protective modifier

Neurocalcin Delta Suppression Protects against Spinal Muscular Atrophy in Humans and across Species by Restoring Impaired Endocytosis

This document is the Accepted Manuscript version of the following article: Riessland et al., 'Neurocalcin Delta Suppression Protects against Spinal Muscular Atrophy in Humans and across Species by Restoring Impaired Endocytosis', The American Journal of Human Genetics, Vol. 100 (2): 297-315, first published online 26 January 2017. The final, published version is available online at doi: http://dx.doi.org/10.1016/j.ajhg.2017.01.005 © 2017 American Society of Human Genetics.Homozygous SMN1 loss causes spinal muscular atrophy (SMA), the most common lethal genetic childhood motor neuron disease. SMN1 encodes SMN, a ubiquitous housekeeping protein, which makes the primarily motor neuron-specific phenotype rather unexpected. SMA-affected individuals harbor low SMN expression from one to six SMN2 copies, which is insufficient to functionally compensate for SMN1 loss. However, rarely individuals with homozygous absence of SMN1 and only three to four SMN2 copies are fully asymptomatic, suggesting protection through genetic modifier(s). Previously, we identified plastin 3 (PLS3) overexpression as an SMA protective modifier in humans and showed that SMN deficit impairs endocytosis, which is rescued by elevated PLS3 levels. Here, we identify reduction of the neuronal calcium sensor Neurocalcin delta (NCALD) as a protective SMA modifier in five asymptomatic SMN1-deleted individuals carrying only four SMN2 copies. We demonstrate that NCALD is a Ca(2+)-dependent negative regulator of endocytosis, as NCALD knockdown improves endocytosis in SMA models and ameliorates pharmacologically induced endocytosis defects in zebrafish. Importantly, NCALD knockdown effectively ameliorates SMA-associated pathological defects across species, including worm, zebrafish, and mouse. In conclusion, our study identifies a previously unknown protective SMA modifier in humans, demonstrates modifier impact in three different SMA animal models, and suggests a potential combinatorial therapeutic strategy to efficiently treat SMA. Since both protective modifiers restore endocytosis, our results confirm that endocytosis is a major cellular mechanism perturbed in SMA and emphasize the power of protective modifiers for understanding disease mechanism and developing therapies.Peer reviewedFinal Accepted Versio