Rac1 and Rac3 GTPases Control Synergistically the Development of Cortical and Hippocampal GABAergic Interneurons

The intracellular mechanisms driving postmitotic development of cortical γ-aminobutyric acid (GABA)ergic interneurons are poorly understood. We have addressed the function of Rac GTPases in cortical and hippocampal interneuron development. Developing neurons express both Rac1 and Rac3. Previous work has shown that Rac1 ablation does not affect the development of migrating cortical interneurons. Analysis of mice with double deletion of Rac1 and Rac3 shows that these GTPases are required during postmitotic interneuron development. The number of parvalbumin-positive cells was affected in the hippocampus and cortex of double knockout mice. Rac depletion also influences the maturation of interneurons that reach their destination, with reduction of inhibitory synapses in both hippocampal CA1 and cortical pyramidal cells. The decreased number of cortical migrating interneurons and their altered morphology indicate a role of Rac1 and Rac3 in regulating the motility of cortical interneurons, thus interfering with their final localization. While electrophysiological passive and active properties of pyramidal neurons including membrane capacity, resting potential, and spike amplitude and duration were normal, these cells showed reduced spontaneous inhibitory currents and increased excitability. Our results show that Rac1 and Rac3 contribute synergistically to postmitotic development of specific populations of GABAergic cells, suggesting that these proteins regulate their migration and differentiation

Itinerários do "estado da arte da educação ambiental superior na Argentina" (Earte-Ar): caminhos, resultados preliminares e desafios

Este artículo tiene un objetivo doble: describe el itinerario recorrido por el grupo argentino (EArte Ar) del Estado del Arte de la Educación Ambiental en América Latina y el Caribe (Arte-ALyC), y presenta los resultados preliminares de su estudio sobre las tesis de maestría y doctorado asociadas al citado campo de conocimiento en el país. Tras enmarcar el estudio en la discusión más amplia alrededor de la educación ambiental, la sección metodológica describe y justifica cada uno de los pasos del proceso iterativo a través del cual se construyeron criterios e instrumentos de recolección y selección de las 52 tesis que constituyen el universo del capítulo argentino de este estudio más amplio. En materia de hallazgos, se muestran dos núcleos de información. El primero, refiere a los repositorios de tesis de posgrado, que en Argentina exhiben un incipiente proceso de digitalización y una alta disparidad de situaciones. El segundo núcleo refiere al universo de tesis de posgrado que abordan la relación procesos educativos y ambiente. Aquí se describe: 1) el mayor peso cuantitativo de tesis pertenecientes a programas de maestría sobre las de doctorado; 2) la predominancia de tesis producidas desde las áreas de las ciencias naturales y biológicas, y en menor medida, desde las ciencias sociales y humanidades; 3) y, por último, el año 2014 como el más fértil en materia de producción de las tesis que interesan al estudio. Aunque se describen algunos temas específicos de la relación procesos educativos y ambiente, el artículo plantea que uno de los desafíos para el mediano plazo es la sistematización rigurosa y el análisis del tipo de temáticas estudiadas en las tesis seleccionadas para el estudio.he present article deals with a double objective. First, we intend to describe the itinerary covered by the Argentine group (EArte-Ar) of the State of the Art of Higher Environmental Education in Latin America and the Caribbean (Arte-ALyC). Secondly, we present the preliminary results of its study on the master’s and doctoral theses associated with the field, as mentioned earlier, of knowledge in the country. After framing the analysisin a broader discussion of environmental education, the methodological section describes and justifies each of the steps of the iterative process, detailing the criteria and instruments employed for collecting and selecting the 52 theses that constitute the final universe of theses built by the Argentinian group. In terms of findings, two nuclei of information are exhibited. The first refers to postgraduate thesis repositories, which indicate an incipient digitization process and a high disparity of situations in Argentina. The second moment refers to the universe of doctoral theses that address the relationship between educational methods and the environment. The second finding describes a 1) greater quantitative weight of theses that belongs to masters’ programs over doctoral ones; 2) the predominance of theses produced from the areas of natural and biological sciences, and to a lesser extent, from the social sciences and humanities; 3) and, finally, 2014 is shown as the most fertile year in terms of production of theses. Although some specific issues related to educational processes and the environment are described, this article states that one of the challenges for the medium term is the rigorous systematization and analysis of the type of issues studied in the theses selected for the study.Este artigo tem um duplo objetivo: descreve o itinerário percorrido pelo grupo argentino (EArte-Ar) do Estado da Arte da Educação Ambiental na América Latina e Caribe (Arte-ALyC) e apresenta os resultados preliminares de seu estudo a partir de dissertações e teses associadas à referida área de conhecimento no país. Após enquadrar o estudo na discussão mais ampla em torno da pesquisa em educação ambiental, a seção metodológica descreve e justifica cada uma das etapas do processo iterativo por meio do qual foram construídos critérios e instrumentos de coleta e seleção das 52 produções acadêmicas que constituem o universo documental deste estudo maior. Em termos de resultados, é possível evidenciar dois núcleos de informação. A primeira refere-se aos repositórios de dissertações e teses, que na Argentina apresentam um processo de digitalização incipiente e uma grande disparidade de situações. O segundo núcleo refere-se ao universo das dissertações e teses que abordam a relação entre os processos educativos e o meio ambiente. Aqui se descreve: 1) o maior peso quantitativo das dissertações de mestrado sobre as teses de doutorado; 2) a predominância de teses produzidas nas áreas das ciências naturais e biológicas e, em menor grau, das ciências sociais e humanas; 3) e, por fim, o ano de 2014 como o mais fértil em termos de produção das teses que interessam ao estudo. Embora sejam descritas algumas questões específicas relacionadas aos processos educacionais e ao meio ambiente, o artigo afirma que um dos desafios para o médio prazo é a rigorosa sistematização e análise do tipo de questões estudadas nas teses selecionadas para o estudo.Fil: Franco, Andrea Daniela. Universidad Nacional de la Patagonia "San Juan Bosco"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: de la Vega Avila Tulian, Candela. Universidad Nacional de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Truchet, Daniela María. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Marinas y Costeras. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Marinas y Costeras; ArgentinaFil: Pereyra, Daniel Augusto. Universidad Nacional de la Patagonia "San Juan Bosco"; ArgentinaFil: Maldonado, José Antonio. Universidad Nacional de Santiago del Estero; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet Noa Sur. Instituto de Estudios para el Desarrollo Social. - Universidad Nacional de Santiago del Estero. Facultad de Humanidades Ciencias Sociales y de la Salud. Instituto de Estudios para el Desarrollo Social; ArgentinaFil: Foradori, María Laura. Universidad Nacional de Villa María; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Ithuralde, Raúl Esteban. Universidad Nacional de Santiago del Estero; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Alvino, Sandra Andrea. Universidad Nacional de Tres de Febrero; ArgentinaFil: Corbetta, Silvina Andrea. Universidad Nacional de Santiago del Estero; Argentina. Universidad Nacional de Hurlingham; Argentin

Quantifying Age-Related Differences in Information Processing Behaviors When Viewing Prescription Drug Labels

Adverse drug events (ADEs) are a significant problem in health care. While effective warnings have the potential to reduce the prevalence of ADEs, little is known about how patients access and use prescription labeling. We investigated the effectiveness of prescription warning labels (PWLs, small, colorful stickers applied at the pharmacy) in conveying warning information to two groups of patients (young adults and those 50+). We evaluated the early stages of information processing by tracking eye movements while participants interacted with prescription vials that had PWLs affixed to them. We later tested participants’ recognition memory for the PWLs. During viewing, participants often failed to attend to the PWLs; this effect was more pronounced for older than younger participants. Older participants also performed worse on the subsequent memory test. However, when memory performance was conditionalized on whether or not the participant had fixated the PWL, these age-related differences in memory were no longer significant, suggesting that the difference in memory performance between groups was attributable to differences in attention rather than differences in memory encoding or recall. This is important because older adults are recognized to be at greater risk for ADEs. These data provide a compelling case that understanding consumers’ attentive behavior is crucial to developing an effective labeling standard for prescription drugs

A path forward in the debate over health impacts of endocrine disrupting chemicals

Several recent publications reflect debate on the issue of “endocrine disrupting chemicals” (EDCs), indicating that two seemingly mutually exclusive perspectives are being articulated separately and independently. Considering this, a group of scientists with expertise in basic science, medicine and risk assessment reviewed the various aspects of the debate to identify the most significant areas of dispute and to propose a path forward. We identified four areas of debate. The first is about the definitions for terms such as “endocrine disrupting chemical”, “adverse effects”, and “endocrine system”. The second is focused on elements of hormone action including “potency”, “endpoints”, “timing”, “dose” and “thresholds”. The third addresses the information needed to establish sufficient evidence of harm. Finally, the fourth focuses on the need to develop and the characteristics of transparent, systematic methods to review the EDC literature. Herein we identify areas of general consensus and propose resolutions for these four areas that would allow the field to move beyond the current and, in our opinion, ineffective debate

Status Update and Interim Results from the Asymptomatic Carotid Surgery Trial-2 (ACST-2)

Objectives: ACST-2 is currently the largest trial ever conducted to compare carotid artery stenting (CAS) with carotid endarterectomy (CEA) in patients with severe asymptomatic carotid stenosis requiring revascularization. Methods: Patients are entered into ACST-2 when revascularization is felt to be clearly indicated, when CEA and CAS are both possible, but where there is substantial uncertainty as to which is most appropriate. Trial surgeons and interventionalists are expected to use their usual techniques and CE-approved devices. We report baseline characteristics and blinded combined interim results for 30-day mortality and major morbidity for 986 patients in the ongoing trial up to September 2012. Results: A total of 986 patients (687 men, 299 women), mean age 68.7 years (SD ± 8.1) were randomized equally to CEA or CAS. Most (96%) had ipsilateral stenosis of 70-99% (median 80%) with contralateral stenoses of 50-99% in 30% and contralateral occlusion in 8%. Patients were on appropriate medical treatment. For 691 patients undergoing intervention with at least 1-month follow-up and Rankin scoring at 6 months for any stroke, the overall serious cardiovascular event rate of periprocedural (within 30 days) disabling stroke, fatal myocardial infarction, and death at 30 days was 1.0%. Conclusions: Early ACST-2 results suggest contemporary carotid intervention for asymptomatic stenosis has a low risk of serious morbidity and mortality, on par with other recent trials. The trial continues to recruit, to monitor periprocedural events and all types of stroke, aiming to randomize up to 5,000 patients to determine any differential outcomes between interventions. Clinical trial: ISRCTN21144362. © 2013 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved

Magnetic Resonance Imaging Correlates of Immune Microenvironment in Glioblastoma

Background: Glioblastoma (GBM) is the most commonly occurring primary malignant brain tumor, and it carries a dismal prognosis. Focusing on the tumor microenvironment may provide new insights into pathogenesis, but no clinical tools are available to do this. We hypothesized that the infiltration of different leukocyte populations in the tumoral and peritumoral brain tissues may be measured by magnetic resonance imaging (MRI). Methods: Pre-operative MRI was combined with immune phenotyping of intraoperative tumor tissue based on flow cytometry of myeloid cell populations that are associated with immune suppression, namely, microglia and bone marrow-derived macrophages (BMDM). These cell populations were measured from the central and marginal areas of the lesion identified intraoperatively with 5-aminolevulinic acid-guided surgery. MRI features (volume, mean and standard deviation of signal intensity, and fractality) were derived from all MR sequences (T1w, Gd+ T1w, T2w, FLAIR) and ADC MR maps and from different tumor areas (contrast- and non-contrast-enhancing tumor, necrosis, and edema). The principal components of MRI features were correlated with different myeloid cell populations by Pearson’s correlation. Results: We analyzed 126 samples from 62 GBM patients. The ratio between BMDM and microglia decreases significantly from the central core to the periphery. Several MRI-derived principal components were significantly correlated (p <0.05, r range: [−0.29, −0.41]) with the BMDM/microglia ratio collected in the central part of the tumor. Conclusions: We report a significant correlation between structural MRI clinical imaging and the ratio of recruited vs. resident macrophages with different immunomodulatory activities. MRI features may represent a novel tool for investigating the microenvironment of GBM

Generation and Characterization of Rac3 Knockout Mice

Rac proteins are members of the Rho family of GTPases involved in the regulation of actin dynamics. The three highly homologous Rac proteins in mammals are the ubiquitous Rac1, the hematopoiesis-specific Rac2, and the least-characterized Rac3. We show here that Rac3 mRNA is widely and specifically expressed in the developing nervous system, with highest concentration at embryonic day 13 in the dorsal root ganglia and ventral spinal cord. At postnatal day 7 Rac3 appears particularly abundant in populations of projection neurons in several regions of the brain, including the fifth layer of the cortex and the CA1-CA3 region of the hippocampus. We generated mice deleted for the Rac3 gene with the aim of analyzing the function of this GTPase in vivo. Rac3 knockout animals survive embryogenesis and show no obvious developmental defects. Interestingly, specific behavioral differences were detected in the Rac3-deficient animals, since motor coordination and motor learning on the rotarod was superior to that of their wild-type littermates. No obvious histological or immunohistological differences were observed at major sites of Rac3 expression. Our results indicate that, in vivo, Rac3 activity is not strictly required for normal development in utero but may be relevant to later events in the development of a functional nervous system

Modulation of MEG resting state networks during rest and natural vision

https://lirias.kuleuven.be/1778492?limo=