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During exercise, skeletal muscle produces reactive oxygen species (ROS) via NADPH oxidase (NOX2) while inducing cellular adaptations associated with contractile activity. The signals involved in this mechanism are still a matter of study. ATP is released from skeletal muscle during electrical stimulation and can autocrinely signal through purinergic receptors; we searched for an influence of this signal in ROS production. The aim of this work was to characterize ROS production induced by electrical stimulation and extracellular ATP. ROS production was measured using two alternative probes; chloromethyl-2,7- dichlorodihydrofluorescein diacetate or electroporation to express the hydrogen peroxide-sensitive protein Hyper. Electrical stimulation (ES) triggered a transient ROS increase in muscle fibers which was mimicked by extracellular ATP and was prevented by both carbenoxolone and suramin; antagonists of pannexin channel and purinergic receptors respectively. In addition, transient ROS increase was prevented by apyrase, an ecto-nucleotidase. MRS2365, a P2Y1 receptor agonist, induced a large signal while UTPyS (P2Y2 agonist) elicited a much smaller signal, similar to the one seen when using ATP plus MRS2179, an antagonist of P2Y1. Protein kinase C (PKC) inhibitors also blocked ES-induced ROS production. Our results indicate that physiological levels of electrical stimulation induce ROS production in skeletal muscle cells through release of extracellular ATP and activation of P2Y1 receptors. Use of selective NOX2 and PKC inhibitors suggests that ROS production induced by ES or extracellular ATP is mediated by NOX2 activated by PKC.  相似文献   
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BackgroundThe overall prognosis of colorectal cancer (CRC) patients is unsatisfactory due to cancer metastasis after operation. This study aims to investigate the clinical significance of plasma osteopontin (OPN) levels as minimally invasive, predictive, and surrogate biomarkers for prognosis of CRC patients.MethodsThis randomized study design consists of pre-operative and post-operative plasma samples from a total of 79 patients. We determined plasma levels of OPN by ELISA and examined their correlation with the clinicopathological parameters of CRC patients. The effects of endogenous and exogenous OPN on CRC metastasis were investigated by examination of the effect on regulators of epithelial to messenchymal transition and migration assay.ResultsOur findings demonstrated for the first time the clinical correlation of plasma OPN with metastasis of CRC patients. High post-operative plasma OPN level (>153.02 ng/ml) associated with development of metastasis after curative resection (p<0.001). Moreover, post-operative plasma OPN level correlated with disease-free survival of CRC patients (p=0.009) and was an independent factor for predicting development of metastasis in CRC patients after curative resection (p=0.036). Our in vitro model showed that OPN ectopic expression induced DLD1 cell migration through Snail and Twist1 overexpression and E-cadherin repression, and secretory OPN level enhanced cell migration.ConclusionsThe results of the current study suggest that post-operative plasma OPN correlated with post-operative metastasis, suggesting that it is a potential non-invasive biomarker for the development of future metastasis in CRC patients. In addition, OPN was shown to be involved in the metastatic process and thus inhibition of OPN is a potential therapeutic approach to treat CRC patients.  相似文献   
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Being Enzo     
Ariel Lefkowitz 《CMAJ》2014,186(14):1093-1094
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We report 24 records of giant armadillo roadkill on Brazilian highways in the Cerrado, Pantanal and Amazon biomes illustrating that highways are a threat to this species. However, we also documented the species using underpasses, demonstrating that these structures could help to reduce the risk of roadkill for giant armadillos.  相似文献   
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To investigate the relationship between atomic topology, vibrational and electronic properties and superconductivity of bismuth, a 216-atom amorphous structure (a-Bi216) was computer-generated using our undermelt-quench approach. Its pair distribution function compares well with experiment. The calculated electronic and vibrational densities of states (eDOS and vDOS, respectively) show that the amorphous eDOS is about 4 times the crystalline at the Fermi energy, whereas for the vDOS the energy range of the amorphous is roughly the same as the crystalline but the shapes are quite different. A simple BCS estimate of the possible crystalline superconducting transition temperature gives an upper limit of 1.3 mK. The e-ph coupling is more preponderant in a-Bi than in crystalline bismuth (x-Bi) as indicated by the λ obtained via McMillan’s formula, λc = 0.24 and experiment λa = 2.46. Therefore with respect to x-Bi, superconductivity in a-Bi is enhanced by the higher values of λ and of eDOS at the Fermi energy.  相似文献   
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Empathy reflects the natural ability to perceive and be sensitive to the emotional states of others, coupled with a motivation to care for their well-being. It has evolved in the context of parental care for offspring, as well as within kinship bonds, to help facilitate group living. In this paper, we integrate the perspectives of evolution, animal behaviour, developmental psychology, and social and clinical neuroscience to elucidate our understanding of the proximate mechanisms underlying empathy. We focus, in particular, on processing of signals of distress and need, and their relation to prosocial behaviour. The ability to empathize, both in animals and humans, mediates prosocial behaviour when sensitivity to others'' distress is paired with a drive towards their welfare. Disruption or atypical development of the neural circuits that process distress cues and integrate them with decision value leads to callous disregard for others, as is the case in psychopathy. The realization that basic forms of empathy exist in non-human animals is crucial for gaining new insights into the underlying neurobiological and genetic mechanisms of empathy, enabling translation towards therapeutic and pharmacological interventions.  相似文献   
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