CB1R chronic intermittent pharmacological activation facilitates amphetamine seeking and self-administration and changes in CB1R/CRFR1 expression in the amygdala and nucleus accumbens in rats.

Patterns of drug ingestion may have a dissimilar impact on the brain, and therefore also the development of drug addiction. One pattern is binge intoxication that refers to the ingestion of a high amount of drug on a single occasion followed by an abstinence period of variable duration. In this study, our goal was to contrast the effect of continuous low amounts with intermittent higher amounts of Arachidonyl-chloro-ethylamide (ACEA), a CB1R agonist, on amphetamine seeking and ingestion, and describe the effects on the expression of CB1R and CRFR1 in the central nucleus of the amygdala (CeA) and in the nucleus accumbens shell (NAcS). Adult male Wistar rats were treated with a daily administration of vehicle or 20 µg of ACEA, or four days of vehicle followed by 100 µg of ACEA on the fifth day, for a total of 30 days. Upon completion of this treatment, the CB1R and CRFR1 expression in the CeA and NAcS was evaluated by immunofluorescence. Additional groups of rats were evaluated for their anxiety levels (elevated plus maze, EPM), amphetamine (AMPH) self-administration (ASA) and breakpoint (A-BP), as well as AMPH-induced conditioned place preference (A-CPP). Results indicated that ACEA induced changes in the CB1R and CRFR1 expression in both the NAcS and CeA. An increase in anxiety-like behavior, ASA, A-BP and A-CPP was also observed. Since the intermittent administration of 100 µg of ACEA induced the most evident changes in most of the parameters studied, we concluded that binge-like ingestion of drugs induces changes in the brain that may make the subject more vulnerable to developing drug addiction.

La utilización del Método de Análisis de Conceptos para la comprensión del concepto de Autorregulación a el Aprendizaje / A utilização do método de análise de conceitos para a compreensão do conceito de aprendizagem autorregulada / The use of concept analysis method to understand the concept of self-regulation learning

Nas últimas décadas, o termo autorregulação tem sido mencionado em pesquisas de diferentes áreas, entre elas a Educação. Devido a essa crescente utilização, questiona-se: quais são os elementos comuns no conceito de aprendizagem autorregulada apresentados em pesquisas internacionais? Neste estudo foram associados os métodos de revisão integrativa e de análise de conceitos. Na primeira etapa da análise de conceitos foi realizado um levantamento de artigos revisados por pares no Portal de Periódicos da CAPES, resultando em 372 trabalhos que permitiram indicar as áreas de utilização do termo. Na segunda etapa, aplicando os critérios de revisão integrativa, foram selecionados 67 trabalhos na base de periódicos ERIC. Entre os fatores comuns foi possível identificar que o processo de aprendizagem autorregulada inclui planejamento, autonomia, implementação de objetivos, metas e estratégias, controle de emoções, gerenciamento do tempo, valorização do conhecimento e execução de tarefas com êxito.

En las últimas décadas, el término autorregulación ha sido mencionado en investigaciones de distintas áreas, entre ellas la Educación. Debido a esa creciente utilización, se cuestiona: ¿cuáles son los elementos comunes en el concepto aprendizaje autorregulado presentados en investigaciones internacionales? En este estudio se asociaron los métodos de revisión integrativa y de análisis de conceptos. En la primera etapa del análisis de conceptos se realizó una recopilación de artículos revisados por pares en el Portal de Periódicos de la CAPES, resultando en 372 estudios que permitieron indicar las áreas de utilización del término. En la segunda etapa, aplicando los criterios de revisión integrativa, se seleccionados 67 estudios en la base de periódicos ERIC. Entre los factores comunes se identificó que el proceso aprendizaje autorregulado incluye planeamiento, autonomía, implementación de objetivos, metas y estrategias, control de emociones, gerenciamiento del tiempo, valoración del conocimiento y ejecución de tareas con éxito.

In recent decades, the term self-regulation has been mentioned in research in different areas, including Education. Due to this growing use, the question is: what are the common elements in the concept of self-regulation learning presented in international research? In this study, integrative review and concept analysis methods were associated. In the first stage of the concept analysis, a survey of peer-reviewed articles was carried out on the CAPES Periodicals Portal, resulting in 372 articles that allowed indicating the areas of use of the term. In the second stage, applying the integrative review criteria, 67 articles were selected from the ERIC journals. Among the common factors, it was possible to identify that the self-regulation learning process includes planning, autonomy, implementation of objectives, goals and strategies, control of emotions, time management, appreciation of knowledge and successful execution of tasks.

Cellular metabolic reprogramming controls sugar appetite in Drosophila.

Cellular metabolic reprogramming is an important mechanism by which cells rewire their metabolism to promote proliferation and cell growth. This process has been mostly studied in the context of tumorigenesis, but less is known about its relevance for nonpathological processes and how it affects whole-animal physiology. Here, we show that metabolic reprogramming in Drosophila female germline cells affects nutrient preferences of animals. Egg production depends on the upregulation of the activity of the pentose phosphate pathway in the germline, which also specifically increases the animal's appetite for sugar, the key nutrient fuelling this metabolic pathway. We provide functional evidence that the germline alters sugar appetite by regulating the expression of the fat-body-secreted satiety factor Fit. Our findings demonstrate that the cellular metabolic program of a small set of cells is able to increase the animal's preference for specific nutrients through inter-organ communication to promote specific metabolic and cellular outcomes.

Metabolic cross-feeding in imbalanced diets allows gut microbes to improve reproduction and alter host behaviour.

The impact of commensal bacteria on the host arises from complex microbial-diet-host interactions. Mapping metabolic interactions in gut microbial communities is therefore key to understand how the microbiome influences the host. Here we use an interdisciplinary approach including isotope-resolved metabolomics to show that in Drosophila melanogaster, Acetobacter pomorum (Ap) and Lactobacillus plantarum (Lp) a syntrophic relationship is established to overcome detrimental host diets and identify Ap as the bacterium altering the host's feeding decisions. Specifically, we show that Ap uses the lactate produced by Lp to supply amino acids that are essential to Lp, allowing it to grow in imbalanced diets. Lactate is also necessary and sufficient for Ap to alter the fly's protein appetite. Our data show that gut bacterial communities use metabolic interactions to become resilient to detrimental host diets. These interactions also ensure the constant flow of metabolites used by the microbiome to alter reproduction and host behaviour.

Commensal bacteria and essential amino acids control food choice behavior and reproduction.

Choosing the right nutrients to consume is essential to health and wellbeing across species. However, the factors that influence these decisions are poorly understood. This is particularly true for dietary proteins, which are important determinants of lifespan and reproduction. We show that in Drosophila melanogaster, essential amino acids (eAAs) and the concerted action of the commensal bacteria Acetobacter pomorum and Lactobacilli are critical modulators of food choice. Using a chemically defined diet, we show that the absence of any single eAA from the diet is sufficient to elicit specific appetites for amino acid (AA)-rich food. Furthermore, commensal bacteria buffer the animal from the lack of dietary eAAs: both increased yeast appetite and decreased reproduction induced by eAA deprivation are rescued by the presence of commensals. Surprisingly, these effects do not seem to be due to changes in AA titers, suggesting that gut bacteria act through a different mechanism to change behavior and reproduction. Thus, eAAs and commensal bacteria are potent modulators of feeding decisions and reproductive output. This demonstrates how the interaction of specific nutrients with the microbiome can shape behavioral decisions and life history traits.

Microenvironment changes (in pH) affect VEGF alternative splicing.

Vascular endothelial growth factor-A (VEGF-A) has several isoforms, which differ in their capacity to bind extracellular matrix proteins and also in their affinity for VEGF receptors. Although the relative contribution of the VEGF isoforms has been studied in tumor angiogenesis, little is known about the mechanisms that regulate the alternative splicing process. Here, we tested microenvironment cues that might regulate VEGF alternative splicing. To test this, we used endometrial cancer cells that produce all VEGF isoforms as a model, and exposed them to varying pH levels, hormones, glucose and CoCl(2) (to mimic hypoxia). Low pH had the most consistent effects in inducing variations in VEGF splicing pattern (VEGF121 increased significantly, p < 0.001, when compared to VEGF145, 165 or 189). This was accompanied by activation of the p38 stress pathway and SR proteins (splicing factors) expression and phosphorylation. SF2/ASF, SRp20 and SRp40 down-regulation by siRNA impaired the effects of pH stimulation, blocking the shift in VEGF isoforms production. Taken together, we show for the first time that acidosis (low pH) regulates VEGF-A alternative splicing, may be through p38 activation and suggest the possible SR proteins involved in this process.

Autocrine VEGF loops, signaling pathways, and acute leukemia regulation.

Data obtained from animal models, and partially confirmed in pre-clinical studies, have provided clear evidence of the importance of angiogenesis for the growth of solid tumors. Similarly, in hematological cancers such as leukemias and lymphomas, the role of angiogenesis has been under intense scrutiny. However, the molecular singularities of leukemia, namely its cellular origin, have suggested a putative role for angiogenesis in these tumors may have distinct features. We and others have shown acute leukemia cells use angiogenic growth factor signaling pathways, namely those activated by vascular endothelial growth factor (VEGF) in autocrine and paracrine fashion. Autocrine and paracrine VEGF stimulation of subsets of leukemias results in cell proliferation, increased survival and migration. This review discusses recent advances in the field of leukemia angiogenesis, focusing on the role of VEGF and its receptors, acting in a paracrine or autocrine manner. We also briefly describe some of the novel anti-angiogenic compounds, namely VEGF blockers, and suggest their use to treat subsets of hematological malignancies may have clinical benefit.