Astrocytes regulate brain extracellular pH via a neuronal activity-dependent bicarbonate shuttle

Brain cells continuously produce and release protons into the extracellular space, with the rate of acid production corresponding to the levels of neuronal activity and metabolism. Efficient buffering and removal of excess H+ is essential for brain function, not least because all the electrogenic and biochemical machinery of synaptic transmission is highly sensitive to changes in pH. Here, we describe an astroglial mechanism that contributes to the protection of the brain milieu from acidification. In vivo and in vitro experiments conducted in rodent models show that at least one third of all astrocytes release bicarbonate to buffer extracellular H+ loads associated with increases in neuronal activity. The underlying signalling mechanism involves activity-dependent release of ATP triggering bicarbonate secretion by astrocytes via activation of metabotropic P2Y1 receptors, recruitment of phospholipase C, release of Ca2+ from the internal stores, and facilitated outward HCO3− transport by the electrogenic sodium bicarbonate cotransporter 1, NBCe1. These results show that astrocytes maintain local brain extracellular pH homeostasis via a neuronal activity-dependent release of bicarbonate. The data provide evidence of another important metabolic housekeeping function of these glial cells

CO2 signaling mediates neurovascular coupling in the cerebral cortex

Neurovascular coupling is a fundamental brain mechanism that regulates local cerebral blood flow (CBF) in response to changes in neuronal activity. Functional imaging techniques are commonly used to record these changes in CBF as a proxy of neuronal activity to study the human brain. However, the mechanisms of neurovascular coupling remain incompletely understood. Here we show in experimental animal models (laboratory rats and mice) that the neuronal activity-dependent increases in local CBF in the somatosensory cortex are prevented by saturation of the CO2-sensitive vasodilatory brain mechanism with surplus of exogenous CO2 or disruption of brain CO2/HCO3− transport by genetic knockdown of electrogenic sodium-bicarbonate cotransporter 1 (NBCe1) expression in astrocytes. A systematic review of the literature data shows that CO2 and increased neuronal activity recruit the same vasodilatory signaling pathways. These results and analysis suggest that CO2 mediates signaling between neurons and the cerebral vasculature to regulate brain blood flow in accord with changes in the neuronal activity

Numerical and experimental analysis of wrinkling during the cup drawing of an AA5042 aluminium alloy

The recent trend to reduce the thickness of metallic sheets used in forming processes strongly increases the likelihood of the occurrence of wrinkling. Thus, in order to obtain defect-free components, the prediction of this kind of defect becomes extremely important in the tool design and selection of process parameters. In this study, the sheet metal forming process proposed as a benchmark in the Numisheet 2014 conference is selected to analyse the influence of the tool geometry on wrinkling behaviour, as well as the reliability of the developed numerical model. The side-wall wrinkling during the deep drawing process of a cylindrical cup in AA5042 aluminium alloy is investigated through finite element simulation and experimental measurements. The material plastic anisotropy is modelled with an advanced yield criterion beyond the isotropic (von Mises) material behaviour. The results show that the shape of the wrinkles predicted by the numerical model is strongly affected by the finite element mesh used in the blank discretization. The accurate modelling of the plastic anisotropy of the aluminium alloy yields numerical results that are in good agreement with the experiments, particularly the shape and location of the wrinkles. The predicted punch force evolution is strongly influenced by the friction coefficient used in the model. Moreover, the two punch geometries provide drawn cups with different wrinkle waves, mainly differing in amplitude.The authors gratefully acknowledge the financial support of the Portuguese Foundation for Science and Technology (FCT) under project PTDC/EMS-TEC/1805/2012. The first author is also grateful to the FCT for the Postdoctoral grant SFRH/BPD/101334/2014 and P.D. Barros is grateful to the FCT for the PhD Grant SFRH/BD/98545/2013info:eu-repo/semantics/publishedVersio

Avaliação das técnicas de massagem e ordenha no tratamento do ingurgitamento mamário por termografia

OBJETIVO: evaluar los métodos de masaje y bombeo en el tratamiento de la congestión mamaria posparto a través de la termografía. MÉTODO: el estudio se realizó en el Banco de Leche Humana de un hospital en Curitiba, Brasil. Se seleccionaron al azar 16 mujeres en periodo de lactancia con congestión con clasificación lobar, ampular y glandular, moderada e intensa. Se compararon los patrones diferenciales de temperatura, antes y después del tratamiento por medio de masaje y bombeo. RESULTADOS: se encontró un degradado negativo de 0,3°C de temperatura entre el pre y post-tratamiento en el grupo experimental. Las mamas con intensa congestión eran 0,7°C más caliente en comparación a aquellos con congestión moderada. CONCLUSIÓN: el masaje y el bombeo electromecánico fueron superiores a los métodos manuales cuando se evaluaron por termografía. REBEC: U1111-1136-9027.OBJETIVO: avaliar técnicas de massagem e ordenha no tratamento do ingurgitamento mamário puerperal, por meio da termografia. MÉTODO: a pesquisa foi realizada no Banco de Leite Humano de um hospital de Curitiba, Brasil. Selecionaram-se, aleatoriamente, 16 lactantes com ingurgitamento com classificação lobar, ampolar e glandular moderado e intenso. Compararam-se os padrões diferenciais de temperatura, antes e após o tratamento realizado, por meio de massagem e ordenha. RESULTADOS: constatou-se um gradiente negativo de 0,3ºC de temperatura entre o pré e o pós-tratamento no grupo experimental. Mamas com ingurgitamento intenso foram 0,7ºC mais quentes quando comparadas com ingurgitamento moderado. CONCLUSÃO: a massagem e ordenha eletromecânicas são superiores às manuais, quando avaliadas por termografia. REBEC: U1111-1136-9027.OBJECTIVE: to evaluate techniques of massage and pumping in the treatment of postpartum breast engorgement through thermography. METHOD: the study was conducted in the Human Milk Bank of a hospital in Curitiba, Brazil. We randomly selected 16 lactating women with engorgement with the classification lobar, ampullary and glandular, moderate and intense. We compared the differential patterns of temperature, before and after the treatment by means of massage and pumping. RESULTS: we found a negative gradient of 0.3°C of temperature between the pre- and post-treatment in the experimental group. Breasts with intense engorgement were 0.7°C warmer when compared with moderate engorgement. CONCLUSION: massage and electromechanical pumping were superior to manual methods when evaluated by thermography. REBEC: U1111-1136-9027

Genome of the Avirulent Human-Infective Trypanosome—Trypanosoma rangeli

Background: Trypanosoma rangeli is a hemoflagellate protozoan parasite infecting humans and other wild and domestic mammals across Central and South America. It does not cause human disease, but it can be mistaken for the etiologic agent of Chagas disease, Trypanosoma cruzi. We have sequenced the T. rangeli genome to provide new tools for elucidating the distinct and intriguing biology of this species and the key pathways related to interaction with its arthropod and mammalian hosts.  Methodology/Principal Findings: The T. rangeli haploid genome is ,24 Mb in length, and is the smallest and least repetitive trypanosomatid genome sequenced thus far. This parasite genome has shorter subtelomeric sequences compared to those of T. cruzi and T. brucei; displays intraspecific karyotype variability and lacks minichromosomes. Of the predicted 7,613 protein coding sequences, functional annotations could be determined for 2,415, while 5,043 are hypothetical proteins, some with evidence of protein expression. 7,101 genes (93%) are shared with other trypanosomatids that infect humans. An ortholog of the dcl2 gene involved in the T. brucei RNAi pathway was found in T. rangeli, but the RNAi machinery is non-functional since the other genes in this pathway are pseudogenized. T. rangeli is highly susceptible to oxidative stress, a phenotype that may be explained by a smaller number of anti-oxidant defense enzymes and heatshock proteins.  Conclusions/Significance: Phylogenetic comparison of nuclear and mitochondrial genes indicates that T. rangeli and T. cruzi are equidistant from T. brucei. In addition to revealing new aspects of trypanosome co-evolution within the vertebrate and invertebrate hosts, comparative genomic analysis with pathogenic trypanosomatids provides valuable new information that can be further explored with the aim of developing better diagnostic tools and/or therapeutic targets

Atmospheric-Pressure Plasma Jet Induces Apoptosis Involving Mitochondria via Generation of Free Radicals

The plasma jet has been proposed as a novel therapeutic method for anticancer treatment. However, its biological effects and mechanism of action remain elusive. Here, we investigated its cell death effects and underlying molecular mechanisms, using air and N2 plasma jets from a micro nozzle array. Treatment with air or N2 plasma jets caused apoptotic death in human cervical cancer HeLa cells, simultaneously with depolarization of mitochondrial membrane potential. In addition, the plasma jets were able to generate reactive oxygen species (ROS), which function as surrogate apoptotic signals by targeting the mitochondrial membrane potential. Antioxidants or caspase inhibitors ameliorated the apoptotic cell death induced by the air and N2 plasma jets, suggesting that the plasma jet may generate ROS as a proapoptotic cue, thus initiating mitochondria-mediated apoptosis. Taken together, our data suggest the potential employment of plasma jets as a novel therapy for cancer