Pharmacological rescue of adult hippocampal neurogenesis in a mouse model of X-linked intellectual disability

Oligophrenin-1 (OPHN1) is a Rho GTPase activating protein whose mutations cause X-linked intellectual disability (XLID). How loss of function of Ophnl affects neuronal development is only partly understood. Here we have exploited adult hippocampal neurogenesis to dissect the steps of neuronal differentiation that are affected by Ophn1 deletion. We found that mice lacking Ophnl display a reduction in the number of newborn neurons in the dentate gyrus. A significant fraction of the Ophn1-deficient newly generated neurons failed to extend an axon towards CM, and showed an altered density of dendritic protrusions. Since Ophnl-deficient mice display overactivation of Rho-associated protein kinase (ROCK) and protein kinase A (PICA) signaling, we administered a clinically approved ROCK/PICA inhibitor (fasudil) to correct the neurogenesis defects. While administration of fasudil was not effective in rescuing axon formation, the same treatment completely restored spine density to control levels, and enhanced the long-term survival of adult-born neurons in mice lacking Ophn1. These results identify specific neurodevelopmental steps that are impacted by Ophn1 deletion, and indicate that they may be at least partially corrected by pharmacological treatment. (C) 2017 The Authors. Published by Elsevier Inc

TrkB signaling directs the incorporation of newly generated periglomerular cells in the adult olfactory bulb.

In the adult rodent brain, the olfactory bulb (OB) is continuously supplied with new neurons which survival critically depends on their successful integration into pre-existing networks. Yet, the extracellular signals that determine the selection which neurons will be ultimately incorporated into these circuits are largely unknown. Here, we show that immature neurons express the catalytic form of the brain-derived neurotrophic factor receptor TrkB [full-length TrkB (TrkB-FL)] only after their arrival in the OB, at the time when inte-gration commences. To unravel the role of TrkB signaling in newborn neurons, we conditionally ablated TrkB-FL in mice via Cre expression in adult neural stem and progenitor cells. TrkB-deficient neurons displayed a marked impairment in dendritic arborization and spine growth. By selectively manipulating the signaling pathways initiated by TrkB in vivo, we identified the transducers Shc/PI3K to be required for dendritic growth, whereas the activation of phospholipase C-was found to be responsible for spine formation. Further-more, long-term genetic fate mapping revealed that TrkB deletion severely compromised the survival of new dopaminergic neurons, leading to a substantial reduction in the overall number of adult-generated periglomerular cells (PGCs), but not of granule cells (GCs). Surprisingly, this loss of dopaminergic PGCs was mirrored by a corresponding increase in the number of calretinin PGCs, suggesting that distinct subsets of adult-born PGCs may respond differentially to common extracellular signals. Thus, our results identify TrkB signaling to be essential for balancing the incorporation of defined classes of adult-born PGCs and not GCs, reflecting their different mode of integration in the OB. \ua9 2013 the authors

KINANTHROPOMETRIC PROFILE OF PORTUGUESE WATER POLO PLAYERS

Our purpose was to describe physical and training background characteristics of Water Polo players and compare them according to their specialized playing positions. The International Working Group of Kinanthropometry guidelines were followed. A one-way unvaried measure ANOVA with Bonferroni post hoc was used to develop a multiple comparisons procedure between the specialized playing positions (α=0.05). It was concluded that the center players presented tendency for the highest values in 8 of the 10 parameters studied. Center backs are older than the drivers and center forwards have a higher BMI than the wingers and the goalkeepers. The somatotype is balanced mesomorph. Center forwards and Drivers tend to get closer endomorphy when compared with the remaining positions

Procesos de alfabetización inicial de jóvenes con Síndrome de Down: hacia la construcción de una inclusión socioeducativa

Este trabajo surge de uno más amplio consistente en un estudio de casos de carácter interdisciplinario con niños y jóvenes con diagnósticos específicos, integrados en escuelas públicas comunes, acerca de cómo aprenden a leer y a escribir con el fin de interpretar las mejores estrategias didácticas y/o terapéuticas, para acompañarlos en ese proceso. En este artículo se informan parcialmente los datos obtenidos a través de una metodología de base psicogenética y sociocultural con tres estudiantes adolescentes con Síndrome de Down en situaciones específicas de lectura y de escritura. La investigación, todavía en curso, pone de manifiesto que los jóvenes indagados desarrollan procesos cognitivos de carácter psicolingüístico complejos y avanzan en el dominio del lenguaje escrito bajo ciertas condiciones didácticas. Estos avances contribuyen a la reflexión acerca de las potencialidades cognitivas de estos estudiantes para el aprendizaje del lenguaje escrito y la incidencia de las modalidades de enseñanza en su posible desarrollo. A partir de este estudio se pretende aportar a la revisión y reformulación de las prácticas educativas en lo que a alfabetización se refiere para lograr la construcción de una educación efectivamente inclusiva.Fil: Báez, Mónica Orfilia. Universidad Nacional de Rosario; ArgentinaFil: Canossa, Cecilia Lucrecia. Universidad Nacional de Rosario; ArgentinaFil: Ponce de Perino, Stella M. Universidad Nacional de Rosario; Argentin

Avaliação de sensibilidade de leveduras neutras a linhagens killer não-Saccharomyces.

XV Congresso Latino-Americano de Viticultura e Enologia E XIII Congresso Brasileiro de Viticultura e Enologia. Bento Gonçalves-RS, 3 a 7 de Novembro de 2015

Learning curves: analysing pace and challenge in four successful puzzle games

The pace at which challenges are introduced in a game has long been identified as a key determinant of both the enjoyment and difficulty experienced by game players, and their ability to learn from game play. In order to understand how to best pace challenges in games, there is great value in analysing games already demonstrated as highly engaging. Play-through videos of four puzzle games (Portal, Portal 2 Co-operative mode, Braid and Lemmings), were observed and analysed using metrics derived from a behavioural psychology understanding of how people solve problems. Findings suggest that; 1) the main skills learned in each game are introduced separately, 2) through simple puzzles that require only basic performance of that skill, 3) the player has the opportunity to practice and integrate that skill with previously learned skills, and 4) puzzles increase in complexity until the next new skill is introduced. These data provide practical guidance for designers, support contemporary thinking on the design of learning structures in games, and suggest future directions for empirical research

Uma Revisão Sistêmica sobre os Plug-ins Moodle para Apoio as Tarefas Docente

This paper describes a study of alternatives to support teaching activities in virtual learning environments. Through a systematic review, we sought to identify plug-ins and papers that discuss or provide optimization solutions to teacher's tasks in Moodle. Altogether, 489 plug-ins and 346 papers of the event Moodle Moot were analyzed. The results demonstrate effort to assist teachers by researchers and developers, but indicate an underutilization of the potential offered by intelligent systems and a decentralization of the solutions presented with the original system

Convective and Wave Signatures in Ozone Profiles Over the Equatorial Americas: Views from TC4 (2007) and SHADOZ

During the months of July-August 2007 NASA conducted a research campaign called the Tropical Composition, Clouds and Climate Coupling (TC4) experiment. Vertical profiles of ozone were measured daily using an instrument known as an ozonesonde, which is attached to a weather balloon and launch to altitudes in excess of 30 km. These ozone profiles were measured over coastal Las Tablas, Panama (7.8N, 80W) and several times per week at Alajuela, Costa Rica (ION, 84W). Meteorological systems in the form of waves, detected most prominently in 100- 300 in thick ozone layer in the tropical tropopause layer, occurred in 50% (Las Tablas) and 40% (Alajuela) of the soundings. These layers, associated with vertical displacements and classified as gravity waves ("GW," possibly Kelvin waves), occur with similar stricture and frequency over the Paramaribo (5.8N, 55W) and San Cristobal (0.925, 90W) sites of the Southern Hemisphere Additional Ozonesondes (SHADOZ) network. The gravity wave labeled layers in individual soundings correspond to cloud outflow as indicated by the tracers measured from the NASA DC-8 and other aircraft data, confirming convective initiation of equatorial waves. Layers representing quasi-horizontal displacements, referred to as Rossby waves, are robust features in soundings from 23 July to 5 August. The features associated with Rossby waves correspond to extra-tropical influence, possibly stratospheric, and sometimes to pollution transport. Comparison of Las Tablas and Alajuela ozone budgets with 1999-2007 Paramaribo and San Cristobal soundings shows that TC4 is typical of climatology for the equatorial Americas. Overall during TC4, convection and associated meteorological waves appear to dominate ozone transport in the tropical tropopause layer