PTEN: A master regulator of neuronal structure, function, and plasticity.

PTEN (phosphatase and tensin homolog on chromosome ten) is a dual protein/lipid phosphatase that dephosphorylates PIP3, thereby inhibiting the AKT/mTOR pathway. This inhibition ultimately decreases protein translation, cell proliferation and cell growth. In the central nervous system, inhibition of PTEN leads to increased stem cell proliferation, somatic, dendritic and axonal growth, accelerated spine maturation, diminished synaptic plasticity, and altered intrinsic excitability. In agreement with these findings, patients carrying single-copy inactivating mutations of PTEN suffer from autism, macrocephaly, mental retardation, and epilepsy.(1) (-) (9) Understanding the mechanisms through which PTEN modulates the structure, function, and plasticity of cortical networks is a major focus of study. Preventing and reversing the changes induced by loss of Pten in model animals will pave the way for treatments in humans

State-Dependent Subnetworks of Parvalbumin-Expressing Interneurons in Neocortex.

Brain state determines patterns of spiking output that underlie behavior. In neocortex, brain state is reflected in the spontaneous activity of the network, which is regulated in part by neuromodulatory input from the brain stem and by local inhibition. We find that fast-spiking, parvalbumin-expressing inhibitory neurons, which exert state-dependent control of network gain and spike patterns, cluster into two stable and functionally distinct subnetworks that are differentially engaged by ascending neuromodulation. One group is excited as a function of increased arousal state; this excitation is driven in part by the increase in cortical norepinephrine that occurs when the locus coeruleus is active. A second group is suppressed during movement when acetylcholine is released into the cortex via projections from the nucleus basalis. These data establish the presence of functionally independent subnetworks of Parvalbumin (PV) cells in the upper layers of the neocortex that are differentially engaged by the ascending reticular activating system

The future use of internet as a communication, information and selling channel, by fast moving consumer goods companies.

A Internet é uma realidade, que tal como a conhecemos hoje, tem apenas 9 anos, e está a passar por um momento de indefinição sobre as suas mais valias como tecnologia que permita criar novos modelos de negócio, ou como um novo canal de comunicação e venda. A evolução da Internet continuará a ser muito rápida, mas existe ainda uma grande dificuldade das empresas em conseguirem perceber como será no futuro e como pode ou deve ser utilizada. Em ambientes estáveis as mudanças são previsíveis, mas em ambientes incertos, como é a Internet, torna-se difícil tomar decisões, implementar estratégias e fazer investimentos que podem ser elevados e de risco quanto ao retorno esperado. Este trabalho tem como objectivo encontrar respostas para algumas das incertezas relacionadas com o uso da Internet pelas empresas que podem vir a condicionar os seus mercados no futuro, bem como ter implicações nos respectivos negócios.Internet is a reality, that as we know it today, has only 9 years, and is now passing trough a moment of doubts about its potential as a technology that allows creating new business models or as a new communication and selling channel. The Internet evolution will keep on being very fast, but still existing high difficulties in organizations to understand how it will be in the future and how it can or should be used. In stable environments changes could be predicted, but in non-stable environments, as Internet, is very difficult for organizations to take decisions, develop new strategies or making high value investments taking the risk of uncertain returns. This work wants to find answers for some of the uncertainties related with the future use of Internet by organizations that could affect their markets, and this way, respective businesses

Integrando el aprendizaje en equipo, el estudio de casos y el aprendizaje basado en problemas en asignaturas de contabilidad: errores básicos y recomendaciones

El presente trabajo describe y analiza cinco años de experiencia en la integración de metodologías distintas pero complementarias en la docencia de Contabilidad, como son el Aprendizaje en Equipo, el Estudio de Casos y el Aprendizaje Basado en Problemas. Durante estos años, en dos asignaturas distintas ¿¿Management Accounting¿ y ¿Advanced Financial Accounting¿, los autores han ido refinando la metodología docente en base a un análisis conjunto de los factores que a priori condicionan la efectividad de estas metodologías y de la experiencia acumulada en años anteriores en la implementación de la metodología.Tres son los objetivos principales del trabajo: evaluar la efectividad en el proceso de aprendizaje de estas metodologías; reflexionar sobre la integración en la práctica real de las metodologías en el aula, basándonos en el análisis de diversas encuestas realizadas a los alumnos y entrevistas selectivas realizadas a los mismos; y elaborar una lista de errores básicos a evitar y de recomendaciones a seguir para facilitar al docente la utilización, integrada o no, de las metodologías antes citadas.Entre las conclusiones fundamentales, señalar que la satisfacción de los alumnos con la metodología seguida crecía cada año, por lo que las modificaciones hechas cada curso parecen efectivas. Igualmente, conocer las competencias iniciales de los alumnos que componen el grupo, es necesario para implementar la metodología con flexibilidad. Finalmente, se apunta la necesidad de incidir más en la formación específica en algunas competencias, como puede ser el trabajo en equipo, para conseguir una mayor eficiencia en el aprendizaje del alumno.Artículo revisado por pare

An inhibitory pull-push circuit in frontal cortex.

Push-pull is a canonical computation of excitatory cortical circuits. By contrast, we identify a pull-push inhibitory circuit in frontal cortex that originates in vasoactive intestinal polypeptide (VIP)-expressing interneurons. During arousal, VIP cells rapidly and directly inhibit pyramidal neurons; VIP cells also indirectly excite these pyramidal neurons via parallel disinhibition. Thus, arousal exerts a feedback pull-push influence on excitatory neurons-an inversion of the canonical push-pull of feedforward input

La imagen y la narrativa como herramientas para el abordaje psicosocial en escenarios de violencia. Departamento del Tolima. Municipios de Ibagué, Villarrica, Chaparral y Ortega

El documento tiene como propósito exponer análisis realizados de manera colaborativa acerca de sucesos violentos ocurridos en Colombia dentro del marco del conflicto armado. Desde una postura analítica el grupo colaborativo presenta informes sobre emergentes psicosociales, características de subjetividad individual y colectiva, impactos bio-psico-socio-culturales, recursos de afrontamiento y elementos resilientes en torno a tres situaciones: 1) el caso de Shimaia de la sección Historias que retornan, realizado por la Comisión de la Verdad; 2) el caso de la masacre de El Salado ocurrida en el departamento de Bolívar; y 3) sucesos ocurridos en 4 municipios del departamento del Tolima: Ibagué, Chaparral, Villarrica y Ortega. Es importante mencionar que desde el rol del psicólogo comunitario y teniendo como base preceptos del enfoque narrativo y la psicología positiva, el grupo expone dentro de este documento tres estrategias de abordaje psicosocial para atender la situación que afrontan los sobrevivientes de la masacre de El Salado, mediante las cuales se busca transformar la realidad de esa comunidad desarrollando acciones psicosociales que contribuyen a potencializar recursos de afrontamiento y su capacidad de resiliencia.The purpose of the document is to present analyzes carried out collaboratively about violent events that occurred in Colombia within the framework of the armed conflict. From an analytical position, the collaborative group presents reports on psychosocial emergents, characteristics of individual and collective subjectivity, bio-psycho-socio-cultural impacts, coping resources and resilient elements around three situations: 1) the case of Shimaia from the section Histories that return, prepared by the Truth Commission; 2) the case of the El Salado massacre that occurred in the department of Bolívar; and 3) events that occurred in 4 municipalities in the department of Tolima: Ibagué, Chaparral, Villarrica and Ortega. It is important to mention that from the role of the community psychologist and based on the precepts of the narrative approach and positive psychology, the collaborative work group exposes within this document three psychosocial approach strategies to address the situation faced by the survivors of the massacre of El Salado, through which it seeks to transform the reality of that community by developing psychosocial actions that contribute to potentiate coping resources and their resilience capacity

T1/T2-weighted ratio in multiple sclerosis: A longitudinal study with clinical associations

Clinically isolated syndrome; Magnetic resonance imaging; Multiple sclerosisSíndrome clínicamente aislado; Imágenes por resonancia magnética; Esclerosis múltipleSíndrome clínicament aïllat; Imatges per ressonància magnètica; Esclerosi múltipleBackground T1w/T2-w ratio has been proposed as a clinically feasible MRI biomarker to assess tissue integrity in multiple sclerosis. However, no data is available in the earliest stages of the disease and longitudinal studies analysing clinical associations are scarce. Objective To describe longitudinal changes in T1-w/T2-w in patients with clinically isolated syndrome (CIS) and multiple sclerosis, and to investigate their clinical associations. Methods T1-w/T2-w images were generated and the mean value obtained in the corresponding lesion, normal-appearing grey (NAGM) and white matter (NAWM) masks. By co-registering baseline to follow-up MRI, evolved lesions were assessed; and by placing the mask of new lesions to the baseline study, the pre-lesional tissue integrity was measured. Results We included 171 CIS patients and 22 established multiple sclerosis patients. In CIS, evolved lesions showed significant T1-w/T2-w increases compared to baseline (+7.6%, P < 0.001). T1-w/T2-w values in new lesions were lower than in pre-lesional tissue (-28.2%, P < 0.001), and pre-lesional tissue was already lower than baseline NAWM (-7.8%, P < 0.001). In CIS at baseline, higher NAGM T1-w/T2-w was associated with multiple sclerosis diagnosis, and longitudinal decreases in NAGM and NAWM T1-w/T2-w were associated with disease activity. In established multiple sclerosis, T1-w/T2-w was inversely correlated with clinical disability and disease duration. Conclusion A decrease in T1-w/T2-w ratio precedes lesion formation. In CIS, higher T1-w/T2-w was associated with multiple sclerosis diagnosis. In established multiple sclerosis, lower T1-w/T2-w values were associated with clinical disability. The possible differential impact of chronic inflammation, iron deposition and demyelination should be considered to interpret these findings.This project was developed as a part of Mateus Boaventura ECTRIMS Clinical Training Fellowship Programme 2018–2019. This study was partially supported by the Project PI18/00823, from the Fondo de Investigación Sanitaria (FIS), Instituto de Salud Carlos III

The Rise and Fall of "Respectable" Spanish Liberalism, 1808-1923: An Explanatory Framework

The article focuses on the reasons behind both the consolidation of what I have termed “respectable” liberalism between the 1830s and the 1840s and its subsequent decline and fall between 1900 and 1923. In understanding both processes I study the links established between “respectable” liberals and propertied elites, the monarchy, and the Church. In the first phase these links served to consolidate the liberal polity. However, they also meant that many tenets of liberal ideology were compromised. Free elections were undermined by the operation of caciquismo, monarchs established a powerful position, and despite the Church hierarchy working with liberalism, the doctrine espoused by much of the Church was still shaped by the Counter-Reformation. Hence, “respectable” liberalism failed to achieve a popular social base. And the liberal order was increasingly denigrated as part of the corrupt “oligarchy” that ruled Spain. Worse still, between 1916 and 1923 the Church, monarch, and the propertied elite increasingly abandoned the liberal Monarchist Restoration. Hence when General Primo de Rivera launched his coup the rug was pulled from under the liberals’ feet and there was no one to cushion the fall

Modifiable risk factors for RA: prevention, better than cure?

Objective. To perform a meta-synthesis of the evidence for modifiable lifestyle risk factors for inflammatory polyarthritis (IP) and RA