Optonongenetic enhancement of activity in primary cortical neurons

It has been recently demonstrated that the exposure of naive neuronal cells to light—at the basis of optogenetic techniques and calcium imaging measurements—may alter neuronal firing. Indeed, understanding the effect of light on nongenetically modified neurons is crucial for a correct interpretation of calcium imaging and optogenetic experiments. Here we investigated the effect of continuous visible LED light exposure (490 nm, 0.18−1.3 mW/mm2) on spontaneous activity of primary neuronal networks derived from the early postnatal mouse cortex. We demonstrated, by calcium imaging and patch clamp experiments, that illumination higher than 1.0 mW/mm2 causes an enhancement of network activity in cortical cultures. We investigated the possible origin of the phenomena by blocking the transient receptor potential vanilloid 4 (TRPV4) channel, demonstrating a complex connection between this temperature-dependent channel and the measured effect. The results presented here shed light on an exogenous artifact, potentially present in all calcium imaging experiments, that should be taken into account in the analysis of fluorescence data

Exploring the use of dimethyl fumarate as microglia modulator for neurodegenerative diseases treatment

The maintenance of redox homeostasis in the brain is critical for the prevention of the development of neurodegenerative diseases. Drugs acting on brain redox balance can be promising for the treatment of neurodegeneration. For more than four decades, dimethyl fumarate (DMF) and other derivatives of fumaric acid ester compounds have been shown to mitigate a number of pathological mechanisms associated with psoriasis and relapsing forms of multiple sclerosis (MS). Recently, DMF has been shown to exert a neuroprotective effect on the central nervous system (CNS), possibly through the modulation of microglia detrimental actions, observed also in multiple brain injuries. In addition to the hypothesis that DMF is linked to the activation of NRF2 and NF-kB transcription factors, the neuroprotective action of DMF may be mediated by the activation of the glutathione (GSH) antioxidant pathway and the regulation of brain iron homeostasis. This review will focus on the role of DMF as an antioxidant modulator in microglia processes and on its mechanisms of action in the modulation of different pathways to attenuate neurodegenerative disease progression

Collective behavior and self-organization in neural rosette morphogenesis

Neural rosettes develop from the self-organization of differentiating human pluripotent stem cells. This process mimics the emergence of the embryonic central nervous system primordium, i.e., the neural tube, whose formation is under close investigation as errors during such process result in severe diseases like spina bifida and anencephaly. While neural tube formation is recognized as an example of self-organization, we still do not understand the fundamental mechanisms guiding the process. Here, we discuss the different theoretical frameworks that have been proposed to explain self-organization in morphogenesis. We show that an explanation based exclusively on stem cell differentiation cannot describe the emergence of spatial organization, and an explanation based on patterning models cannot explain how different groups of cells can collectively migrate and produce the mechanical transformations required to generate the neural tube. We conclude that neural rosette development is a relevant experimental 2D in-vitro model of morphogenesis because it is a multi-scale self-organization process that involves both cell differentiation and tissue development. Ultimately, to understand rosette formation, we first need to fully understand the complex interplay between growth, migration, cytoarchitecture organization, and cell type evolution

Leaf Fragment Identification of Subtropical Native Grass Species

The present study was carried out to characterise leaf fragments of important plant species of a subtropical native sward in the southernmost state of Brazil. Thirteen important grass species were collected from April to May 1999. Both sides of the leaves were observed using a stereomicroscope. In addition, two approaches were tested to provide a clearer characterisation of the leaves of each species: the leaves were either dried or frozen. The kind and number of veins, the kind and number of hair, and the arrangements and number of stomates on both sides of each leaf are the most useful characteristics to differentiate fragments of native grass species’ leaves. These characteristics can be more easily observed when the plant material is dried

Dinámica lateral de una dupla ferroviaria articulada

Las duplas ferroviarias articuladas son vehículos modulares conformados por dos coches y una unidad motriz (UM) situada entre ellos. Cada coche exhibe la particularidad de poseer sólo un bogie en un extremo y estar apoyado sobre la UM. Estos tipos de vehículos presentan condiciones particulares de inestabilidad debido a la naturaleza propia de la configuración utilizada. Todo fenómeno producido en la dinámica del sistema es magnificado por la complejidad de la distribución de la formación analizada. El módulo de propulsión (UM) constituye el componente con mayor influencia sobre la dinámica de los coches conducidos, generando así, el interés de su estudio. El objetivo general es identificar la gama de parámetros de prueba necesarios para la evaluación del rendimiento del vehículo y determinar las condiciones críticas que limitan la velocidad longitudinal de desplazamiento, lo cual produce la reducción del confort de marcha y afectan la seguridad frente al descarrilamiento. Una limitación importante en el transporte ferroviario es el producido por las vibraciones laterales como respuesta al contacto con la vía. Dichas vibraciones en los coches de pasajeros reducen el confort de marcha, y son capaces de generar un severo desgaste tanto de los rieles como en las ruedas del bogie. Bajo condiciones extremas, estas oscilaciones pueden dar lugar al descarrilamiento de la formación. Existen dos conceptos básicos a considerar en el comportamiento dinámico lateral de vehículos ferroviarios: es el fenómeno conocido como hunting, y la velocidad crítica. El primero de ellos, refiere a la utilización de una sección cónica variable en los perfiles de ruedas, es un movimiento armónico, periódico y oscilante. El segundo, es la velocidad crítica, la cual puede definirse como la velocidad a partir de la cual el vehículo presenta un cambio considerable en su comportamiento dinámico. A bajas velocidades (< 30 km/h), el fenómeno se observa como una oscilación del coche, de gran amplitud, baja frecuencia, a velocidades más elevadas (> 70 km/h), aumenta la probabilidad de producirse una oscilación de aparición violenta, alta frecuencia, generando el peligro de un eventual descarrilamiento. En el presente estudio, se ha realizado el análisis dinámico de la dupla articulada denominada “Alerce”, de la empresa EMEPA. Dicha dupla se encuentra actualmente en funcionamiento como transporte de pasajeros en la línea Belgrano Norte, en el área metropolitana

Neuroinflammatory processes, A1 astrocyte activation and protein aggregation in the retina of Alzheimer’s disease patients, possible biomarkers for early diagnosis

Alzheimer's disease (AD), a primary cause of dementia in the aging population, is characterized by extracellular amyloid-beta peptides aggregation, intracellular deposits of hyperphosphorylated tau, neurodegeneration and glial activation in the brain. It is commonly thought that the lack of early diagnostic criteria is among the main causes of pharmacological therapy and clinical trials failure; therefore, the actual challenge is to define new biomarkers and non-invasive technologies to measure neuropathological changes in vivo at pre-symptomatic stages. Recent evidences obtained from human samples and mouse models indicate the possibility to detect protein aggregates and other pathological features in the retina, paving the road for non-invasive rapid detection of AD biomarkers. Here, we report the presence of amyloid beta plaques, tau tangles, neurodegeneration and detrimental astrocyte and microglia activation according to a disease associated microglia phenotype (DAM). Thus, we propose the human retina as a useful site for the detection of cellular and molecular changes associated with Alzheimer's disease

Pseudo cardiac tamponade in the setting of excess pericardial fat

Cardiac tamponade is the phenomenon of hemodynamic compromise caused by a pericardial effusion. Following a myocardial infarction, the most common causes of pericardial fluid include early pericarditis, Dressler's syndrome, and hemopericardium secondary to a free wall rupture. On transthoracic echocardiography, pericardial fluid appears as an echo-free space in between the visceral and parietal layers of the pericardium. Pericardial fat has a similar appearance on echocardiography and it may be difficult to discern the two entities. We present a case of a post-MI patient demonstrating pseudo tamponade physiology in the setting of excessive pericardial fat

Proliferation Index: A Continuous Model to Predict Prognosis in Patients with Tumours of the Ewing's Sarcoma Family

The prognostic value of proliferation index (PI) and apoptotic index (AI), caspase-8, -9 and -10 expression have been investigated in primary Ewing's sarcoma family of tumours (ESFT). Proliferating cells, detected by immunohistochemistry for Ki-67, were identified in 91% (91/100) of tumours with a median PI of 14 (range 0–87). Apoptotic cells, identified using the TUNEL assay, were detected in 96% (76/79) of ESFT; the median AI was 3 (range 0–33). Caspase-8 protein expression was negative (0) in 14% (11/79), low (1) in 33% (26/79), medium (2) in 38% (30/79) and high (3) in 15% (12/79) of tumours, caspase-9 expression was low (1) in 66% (39/59) and high (3) in 34% (20/59), and caspase-10 protein was low (1) in 37% (23/62) and negative (0) in 63% (39/62) of primary ESFT. There was no apparent relationship between caspase-8, -9 and -10 expression, PI and AI. PI was predictive of relapse-free survival (RFS; p = 0.011) and overall survival (OS; p = <0.001) in a continuous model, whereas AI did not predict outcome. Patients with tumours expressing low levels of caspase-9 protein had a trend towards a worse RFS than patients with tumours expressing higher levels of caspase-9 protein (p = 0.054, log rank test), although expression of caspases-8, -9 and/or -10 did not significantly predict RFS or OS. In a multivariate analysis model that included tumour site, tumour volume, the presence of metastatic disease at diagnosis, PI and AI, PI independently predicts OS (p = 0.003). Consistent with previous publications, patients with pelvic tumours had a significantly worse OS than patients with tumours at other sites (p = 0.028); patients with a pelvic tumour and a PI≥20 had a 6 fold-increased risk of death. These studies advocate the evaluation of PI in a risk model of outcome for patients with ESFT