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

Transit Timing and Duration Variations for the Discovery and Characterization of Exoplanets

Transiting exoplanets in multi-planet systems have non-Keplerian orbits which can cause the times and durations of transits to vary. The theory and observations of transit timing variations (TTV) and transit duration variations (TDV) are reviewed. Since the last review, the Kepler spacecraft has detected several hundred perturbed planets. In a few cases, these data have been used to discover additional planets, similar to the historical discovery of Neptune in our own Solar System. However, the more impactful aspect of TTV and TDV studies has been characterization of planetary systems in which multiple planets transit. After addressing the equations of motion and parameter scalings, the main dynamical mechanisms for TTV and TDV are described, with citations to the observational literature for real examples. We describe parameter constraints, particularly the origin of the mass/eccentricity degeneracy and how it is overcome by the high-frequency component of the signal. On the observational side, derivation of timing precision and introduction to the timing diagram are given. Science results are reviewed, with an emphasis on mass measurements of transiting sub-Neptunes and super-Earths, from which bulk compositions may be inferred.Comment: Revised version. Invited review submitted to 'Handbook of Exoplanets,' Exoplanet Discovery Methods section, Springer Reference Works, Juan Antonio Belmonte and Hans Deeg, Eds. TeX and figures may be found at https://github.com/ericagol/TTV_revie

The development and application of a new tool to assess the adequacy of the content and timing of antenatal care

Abstract Background: Current measures of antenatal care use are limited to initiation of care and number of visits. This study aimed to describe the development and application of a tool to assess the adequacy of the content and timing of antenatal care. Methods: The Content and Timing of care in Pregnancy (CTP) tool was developed based on clinical relevance for ongoing antenatal care and recommendations in national and international guidelines. The tool reflects minimal care recommended in every pregnancy, regardless of parity or risk status. CTP measures timing of initiation of care, content of care (number of blood pressure readings, blood tests and ultrasound scans) and whether the interventions were received at an appropriate time. Antenatal care trajectories for 333 pregnant women were then described using a standard tool (the APNCU index), that measures the quantity of care only, and the new CTP tool. Both tools categorise care into 4 categories, from ‘Inadequate’ (both tools) to ‘Adequate plus’ (APNCU) or ‘Appropriate’ (CTP). Participants recorded the timing and content of their antenatal care prospectively using diaries. Analysis included an examination of similarities and differences in categorisation of care episodes between the tools. Results: According to the CTP tool, the care trajectory of 10,2% of the women was classified as inadequate, 8,4% as intermediate, 36% as sufficient and 45,3% as appropriate. The assessment of quality of care differed significantly between the two tools. Seventeen care trajectories classified as ‘Adequate’ or ‘Adequate plus’ by the APNCU were deemed ‘Inadequate’ by the CTP. This suggests that, despite a high number of visits, these women did not receive the minimal recommended content and timing of care. Conclusions: The CTP tool provides a more detailed assessment of the adequacy of antenatal care than the current standard index. However, guidelines for the content of antenatal care vary, and the tool does not at the moment grade over-use of interventions as ‘Inappropriate’. Further work needs to be done to refine the content items prior to larger scale testing of the impact of the new measure

Physical activity and medicine use: evidence from a population-based study

BACKGROUND: Few studies have investigated the association between physical activity practice and medicine use; data from these studies are inconsistent. The aim of this study was to evaluate the association between level of physical activity and medicine use in adults aged 20 years or more. METHODS: A population-based cross-sectional study was carried out in the first semester of 2002 in the urban area of Pelotas; a medium-sized Southern Brazilian city. Physical activity was assessed with the short version of the International Physical Activity Questionnaire. A physical activity score was created as the weekly time spent in moderate-intensity activities plus twice the weekly time spent in vigorous-intensity activities. Medicine use in the 15 days prior to the interview was also assessed. Adjusted analyses taking into account the sampling design was carried out using Poisson regression. Wald tests for heterogeneity and linear trend were used to calculate significance. RESULTS: Out of the 3,182 individuals interviewed, 41% were not sufficiently active according to current physical activity guidelines. Only 34% of the subjects did not use medicines in the previous 15 days, and 18% used three or more drugs in the same period. Level of physical activity was inversely associated with the number of medicines used both in the crude and in the adjusted analyses. CONCLUSION: There are well-documented benefits of physical activity for several chronic diseases in the literature. Data from the present study suggest that medicine use is also positively affected by physical activity behavior

Direct enzymatic esterification of cotton and Avicel with wild-type and engineered cutinases

In this work, the surface of cellulose, either Avicel or cotton fabric, was modified using cutinases without any previous treatment to swell or to solubilise the polymer. Aiming further improvement of cutinase ester synthase activity on cellulose, an engineered cutinase was investigated. Wild-type cutinase from Fusarium solani and its fusion with the carbohydrate-binding module N1 from Cellulomonas fimi were able to esterify the hydroxyl groups of cellulose with distinct efficiencies depending on the acid substrate/solvent system used, as shown by titration and by ATR-FTIR. The carbonyl stretching peak area increased significantly after enzymatic treatment during 72 h at 30 °C. Cutinase treatment resulted in relative increases of 31 and 9 % when octanoic acid and vegetable oil were used as substrates, respectively. Cutinase-N1 treatment resulted in relative increases of 11 and 29 % in the peak area when octanoic acid and vegetable oil were used as substrates, respectively. The production and application of cutinase fused with the domain N1 as a cellulose ester synthase, here reported for the first time, is therefore an interesting strategy to pursuit.This work was co-funded by the European Social Fund through the management authority POPH and FCT, Postdoctoral fellowship reference: SFRH/BPD/47555/2008. The authors also want to thank Doctor Raul Machado for his valuable help on FTIR spectral data treatment