ATP is released from nerve terminals and from activated muscle fibres on stimulation of the rat phrenic nerve

Nerve stimulation increases the concentration of ATP in the synaptic cleft, which can act as a neurotransmitter or as a presynaptic neuromodulator. Using the luciferin-luciferase assay, we observed that the extracellular concentration of ATP increased by 11-26 nM over a basal concentration of 6 nM, in a frequency dependent manner (1-5 Hz), in the adult rat phrenic nerve-hemidiaphragm preparation. This ATP release depends on nerve activity since it was abolished by tetrodotoxin (1 [mu]M) and is strictly dependent on the presence of extracellular calcium. However, more than half of this nerve-evoked release of ATP is derived from activated muscle fibres since the selective post-synaptic nicotinic receptor antagonist, [alpha]-bungarotoxin (1 [mu]M), inhibited by over 60% the evoked release of ATP. The presently observed post-synaptic release of ATP together with the previously reported lack of post-synaptic effects of ATP and to the ability of ATP to act as a presynaptic modulator open the possibility that ATP may behave as a retrograde messenger at this neuromuscular junction.http://www.sciencedirect.com/science/article/B6T0G-47S6YPN-X/1/e09fe63a6ed4383fc2ed5996ece6ac4

Constructal design method dealing with stiffened plates and symmetry boundaries

A new computational procedure for modelling the structural behavior of stiffened plates with symmetry boundary conditions is here presented. It uses two-dimensional finite elements as a way to decrease computational time without losing precision thanks to a relatively small number of elements applied for analyzing out-of-plane displacements (deflections) and stresses. Adding, the constructal design method was included in the procedure, together with the exhaustive search technique, with the scope to optimize the stress/strain status of stiffened plates by design changes. For the purpose, a reference plate without stiffeners was initially design and used as starting point. Part of the volume was reshaped into stiffeners: thickness was reduced maintaining unchanged weight, length and width. The main goal was to minimize strains and stresses by geometric changes. Results demonstrated that, thanks to this design procedure, it is always possible to find an adequate geometry transformation from reference plate into stiffeners, allowing significant improvements in mechanical behavior

Produção de painéis compensados com resina fenólica e melamínica sem formaldeído

O objetivo desta pesquisa foi avaliar o potencial técnico de duas resinas sem formaldeído para a produção de compensados laminados para ambiente interno e externo não abrigado. Para tanto, as resinas foram comparadas com as tradicionalmente utilizadas pelo setor. O plano experimental foi composto por 05 tratamentos, sendo: com resina fenol sem formaldeído (T1) e com formaldeído (T2), com resina melamina uréia com formaldeído (T3) e sem formaldeído (T4), e com resina uréia formaldeído (T5). Foram produzidos painéis compensados laminados com 07 lâminas de 2,7 mm, com composição do adesivo e parâmetros de processo conforme recomendado pelos fabricantes das resinas. Os resultados das propriedades tecnológicas dos painéis foram inicialmente submetidos a testes de normalidade dos dados e homogeneidade das variâncias, e na sequência avaliados por meio da análise de variância e teste de Scott Knot a 95% de probabilidade. Observou-se que para ambiente externo não abrigado, a resina melamínica uréia sem formaldeído demonstrou potencial de utilização; já a resina fenólica sem formaldeído (em pó) apresentou resultados pouco expressivos. Para ambiente interno, a resina melamínica uréia sem formaldeído se apresentou como potencial técnico para substituição da uréia formaldeído

GLUT1 expression in malignant tumors and its use as an immunodiagnostic marker

OBJECTIVE: To analyze glucose transporter 1 expression patterns in malignant tumors of various cell types and evaluate their diagnostic value by immunohistochemistry. INTRODUCTION: Glucose is the major source of energy for cells, and glucose transporter 1 is the most common glucose transporter in humans. Glucose transporter 1 is aberrantly expressed in several tumor types. Studies have implicated glucose transporter 1 expression as a prognostic and diagnostic marker in tumors, primarily in conjunction with positron emission tomography scan data. METHODS: Immunohistochemistry for glucose transporter 1 was performed in tissue microarray slides, comprising 1955 samples of malignant neoplasm from different cell types. RESULTS: Sarcomas, lymphomas, melanomas and hepatoblastomas did not express glucose transporter 1. Fortyseven per cent of prostate adenocarcinomas were positive, as were 29% of thyroid, 10% of gastric and 5% of breast adenocarcinomas. Thirty-six per cent of squamous cell carcinomas of the head and neck were positive, as were 42% of uterine cervix squamous cell carcinomas. Glioblastomas and retinoblastomas showed membranous glucose transporter 1 staining in 18.6% and 9.4% of all cases, respectively. Squamous cell carcinomas displayed membranous expression, whereas adenocarcinomas showed cytoplasmic glucose transporter 1 expression. CONCLUSION: Glucose transporter 1 showed variable expression in various tumor types. Its absence in sarcomas, melanomas, hepatoblastomas and lymphomas suggests that other glucose transporters mediate the glycolytic pathway in these tumors. The data suggest that glucose transporter 1 is a valuable immunohistochemical marker that can be used to identify patients for evaluation by positron emission tomography scan. The function of cytoplasmic glucose transporter 1 in adenocarcinomas must be further examined

Neuromodulation and neuroprotective effects of chlorogenic acids in excitatory synapses of mouse hippocampal slices

The increased healthspan afforded by coffee intake provides novel opportunities to identify new therapeutic strategies. Caffeine has been proposed to afford benefits through adenosine A2A receptors, which can control synaptic dysfunction underlying some brain disease. However, decaffeinated coffee and other main components of coffee such as chlorogenic acids, also attenuate brain dysfunction, although it is unknown if they control synaptic function. We now used electrophysiological recordings in mouse hippocampal slices to test if realistic concentrations of chlorogenic acids directly affect synaptic transmission and plasticity. 3-(3,4-dihydroxycinnamoyl)quinic acid (CA, 1–10 μM) and 5-O-(trans-3,4-dihydroxycinnamoyl)-D-quinic acid (NCA, 1–10 μM) were devoid of effect on synaptic transmission, paired-pulse facilitation or long-term potentiation (LTP) and long-term depression (LTD) in Schaffer collaterals-CA1 pyramidal synapses. However, CA and NCA increased the recovery of synaptic transmission upon re-oxygenation following 7 min of oxygen/glucose deprivation, an in vitro ischemia model. Also, CA and NCA attenuated the shift of LTD into LTP observed in hippocampal slices from animals with hippocampal-dependent memory deterioration after exposure to β-amyloid 1–42 (2 nmol, icv), in the context of Alzheimer’s disease. These findings show that chlorogenic acids do not directly affect synaptic transmission and plasticity but can indirectly affect other cellular targets to correct synaptic dysfunction. Unraveling the molecular mechanisms of action of chlorogenic acids will allow the design of hitherto unrecognized novel neuroprotective strategies

Caffeine Consumption Prevents Diabetes-Induced Memory Impairment and Synaptotoxicity in the Hippocampus of NONcZNO10/LTJ Mice

Diabetic conditions are associated with modified brain function, namely with cognitive deficits, through largely undetermined processes. More than understanding the underlying mechanism, it is important to devise novel strategies to alleviate diabetes-induced cognitive deficits. Caffeine (a mixed antagonist of adenosine A1 and A2A receptors) emerges as a promising candidate since caffeine consumption reduces the risk of diabetes and effectively prevents memory deficits caused by different noxious stimuli. Thus, we took advantage of a novel animal model of type 2 diabetes to investigate the behavioural, neurochemical and morphological modifications present in the hippocampus and tested if caffeine consumption might prevent these changes. We used a model closely mimicking the human type 2 diabetes condition, NONcNZO10/LtJ mice, which become diabetic at 7–11 months when kept under an 11% fat diet. Caffeine (1 g/l) was applied in the drinking water from 7 months onwards. Diabetic mice displayed a decreased spontaneous alternation in the Y-maze accompanied by a decreased density of nerve terminal markers (synaptophysin, SNAP25), mainly glutamatergic (vesicular glutamate transporters), and increased astrogliosis (GFAP immunoreactivity) compared to their wild type littermates kept under the same diet. Furthermore, diabetic mice displayed up-regulated A2A receptors and down-regulated A1 receptors in the hippocampus. Caffeine consumption restored memory performance and abrogated the diabetes-induced loss of nerve terminals and astrogliosis. These results provide the first evidence that type 2 diabetic mice display a loss of nerve terminal markers and astrogliosis, which is associated with memory impairment; furthermore, caffeine consumption prevents synaptic dysfunction and astrogliosis as well as memory impairment in type 2 diabetes

Selective Decrease of Components of the Creatine Kinase System and ATP Synthase Complex in Chronic Chagas Disease Cardiomyopathy

Chronic Chagas disease cardiomyopathy (CCC) affects millions in endemic areas and is presenting in growing numbers in the USA and European countries due to migration currents. Clinical progression, length of survival and overall prognosis are significantly worse in CCC patients when compared to patients with dilated cardiomyopathy of non-inflammatory etiology. Impairment of energy metabolism seems to play a role in heart failure due to cardiomyopathies. Herein, we have analyzed energy metabolism enzymes in myocardium samples of CCC patients comparing to other non-inflammatory cardiomyopathies. We found that myocardial tissue from CCC patients displays a significant reduction of both myocardial protein levels of ATP synthase alpha and creatine kinase enzyme activity, in comparison to control heart samples, as well as idiopathic dilated cardiomyopathy and ischemic cardiomyopathy. Our results suggest that CCC myocardium displays a selective energetic deficit, which may play a role in the reduced heart function observed in such patients

Currículos socioemocionais, habilidades do século XXI e o investimento econômico na educação: as novas políticas curriculares em exame

RESUMO Nos regimes de implementação das políticas curriculares contemporâneas, noções como competências socioemocionais, habilidades do século XXI, paradigma holístico, currículo socioemocional e abordagem transversal tornaram-se recorrentes nos debates educacionais mobilizados pelos diferentes sistemas de ensino. O presente artigo é decorrente de uma pesquisa que, a partir do campo de Estudos das Políticas de Currículo, tem como objetivo problematizar a difusão de um modelo contemporâneo de currículo socioemocional que toma os estudantes como capital humano a ser investido. Para tanto, definiu-se como corpus de análise do artigo um modelo de currículo socioemocional colocado em ação no Rio de Janeiro, no qual são examinados: a) as racionalidades governamentais que operam na implementação do currículo; b) os sentidos de conhecimento escolar e formação humana engendrados na trama discursiva curricular. O artigo apresenta, então, um diagnóstico das articulações entre infância, escolarização e neoliberalismo. A seguir, discute alguns desdobramentos subjetivos da teorização contemporânea nomeada como Big Five, analisando a promoção de um modelo de currículo socioemocional colocado em ação no Rio de Janeiro. Por fim, a partir das análises, infere que a indústria educacional contemporânea, motivada pelo imperativo de investimento econômico em educação, tem planejado tecnologias que operam no mapeamento e na tentativa de potencialização das competências socioemocionais dos alunos, tendo em vista sua qualificação enquanto capital humano