Modulation of ion channels by hydrogen sulfide

Increasing current awareness and understanding of the roles and mechanisms of action of ion channel regulation by H(2)S will open opportunities for therapeutic intervention with clear clinical benefits, and inform future therapies. In addition, more sensitive methods for detecting relevant physiological concentrations of H(2)S will allow for clarification of specific ion channel regulation with reference to physiological or pathophysiological settings.

The detection of atmospheric rivers in atmospheric reanalyses and their links to British winter floods and the large-scale climatic circulation

Atmospheric Rivers (ARs), narrow plumes of enhanced moisture transport in the lower troposphere, are a key synoptic feature behind winter flooding in midlatitude regions. This article develops an algorithm which uses the spatial and temporal extent of the vertically integrated horizontal water vapor transport for the detection of persistent ARs (lasting 18 h or longer) in five atmospheric reanalysis products. Applying the algorithm to the different reanalyses in the vicinity of Great Britain during the winter half-years of 1980–2010 (31 years) demonstrates generally good agreement of AR occurrence between the products. The relationship between persistent AR occurrences and winter floods is demonstrated using winter peaks-over-threshold (POT) floods (with on average one flood peak per winter). In the nine study basins, the number of winter POT-1 floods associated with persistent ARs ranged from approximately 40 to 80%. A Poisson regression model was used to describe the relationship between the number of ARs in the winter half-years and the large-scale climate variability. A significant negative dependence was found between AR totals and the Scandinavian Pattern (SCP), with a greater frequency of ARs associated with lower SCP values.

Future changes in atmospheric rivers and their implications for winter flooding in Britain

Within the warm conveyor belt of extra-tropical cyclones, atmospheric rivers (ARs) are the key synoptic features which deliver the majority of poleward water vapour transport, and are associated with episodes of heavy and prolonged rainfall. ARs are responsible for many of the largest winter floods in the mid-latitudes resulting in major socioeconomic losses; for example, the loss from United Kingdom (UK) flooding in summer/winter 2012 is estimated to be about $1.6 billion in damages. Given the well-established link between ARs and peak river flows for the present day, assessing how ARs could respond under future climate projections is of importance in gauging future impacts from flooding. We show that North Atlantic ARs are projected to become stronger and more numerous in the future scenarios of multiple simulations from five state-of-the-art global climate models (GCMs) in the fifth Climate Model Intercomparison Project (CMIP5). The increased water vapour transport in projected ARs implies a greater risk of higher rainfall totals and therefore larger winter floods in Britain, with increased AR frequency leading to more flood episodes. In the high emissions scenario (RCP8.5) for 2074–2099 there is an approximate doubling of AR frequency in the five GCMs. Our results suggest that the projected change in ARs is predominantly a thermodynamic response to warming resulting from anthropogenic radiative forcing.

Phenolic acid intake, delivered via moderate champagne wine consumption, improves spatial working memory via the modulation of hippocampal and cortical protein expression/activation.

Aims: While much data exist for the effects of flavonoid-rich foods on spatial memory in rodents, there are no such data for foods/beverages predominantly containing hydroxycinnamates and phenolic acids. To address this, we investigated the effects of moderate Champagne wine intake, which is rich in these components, on spatial memory and related mechanisms relative to the alcohol- and energy-matched controls. Results: In contrast to the isocaloric and alcohol-matched controls, supplementation with Champagne wine (1.78 ml/kg BW, alcohol 12.5% vol.) for 6 weeks led to an improvement in spatial working memory in aged rodents. Targeted protein arrays indicated that these behavioral effects were paralleled by the differential expression of a number of hippocampal and cortical proteins (relative to the isocaloric control group), including those involved in signal transduction, neuroplasticity, apoptosis, and cell cycle regulation. Western immunoblotting confirmed the differential modulation of brain-derived neurotrophic factor, cAMP response-element-binding protein (CREB), p38, dystrophin, 2',3'-cyclic-nucleotide 3'-phosphodiesterase, mammalian target of rapamycin (mTOR), and Bcl-xL in response to Champagne supplementation compared to the control drink, and the modulation of mTOR, Bcl-xL, and CREB in response to alcohol supplementation. Innovation: Our data suggest that smaller phenolics such as gallic acid, protocatechuic acid, tyrosol, caftaric acid, and caffeic acid, in addition to flavonoids, are capable of exerting improvements in spatial memory via the modulation in hippocampal signaling and protein expression. Conclusion: Changes in spatial working memory induced by the Champagne supplementation are linked to the effects of absorbed phenolics on cytoskeletal proteins, neurotrophin expression, and the effects of alcohol on the regulation of apoptotic events in the hippocampus and cortex. Antioxid. Redox Signal. 00, 000-000.

Increased whole grain consumption does not affect blood biochemistry, body composition or gut microbiology in healthy low habitual whole grain consumers

Background Whole grain (WG) foods have been suggested to reduce the risk of cardiovascular disease, but studies are inconsistent and effects on cardiovascular risk markers are not clear. Objective The objective of this study was to assess the impact of increasing WG consumption to at least 80 g/d on overall dietary intake, body composition, blood pressure (BP), blood lipids, blood glucose, gastrointestinal microbiology and gastrointestinal symptoms in healthy, middle-age adults with habitual WG intake < 24 g/d. The trial was registered as ISRCTN36521837. Methods Eligible subjects (12 men, 21 women, aged 40-65 y and BMI 20-35 kg/m2) were identified using food frequency questionnaires and subsequently completed 3-day food diaries (3DFD) to confirm habitual WG consumption. Subjects consumed diets high in WG (> 80 g/d) or low in WG (< 16 g/d, refined grain [RG] diet) in a crossover study, with 6-week intervention periods, separated by a 4-week washout. Adherence was achieved by specific dietary advice and provision of a range of cereal food products. The 3DFD, diet compliance diaries and plasma alkylresorcinols (ARs) were used to verify compliance. Results On the WG intervention, consumption increased from 28 g/d to 168 g/d (P < 0.001), accompanied by an increase in plasma ARs (P < 0.001) and total fiber intake (P < 0.001), without any effect on energy or other macronutrients. While there were no effects on studied parameters, there were trends towards increased 24 h fecal weight (P = 0.08) and reduction in body weight (P = 0.10) and BMI (P = 0.08) during the WG compared to the RG period. Conclusion A combination of dietary advice and provision of commercially available food items enabled subjects with a low-moderate habitual consumption of WG to substantially increase their WG intake, but there was little effect on blood biochemical parameters, body composition, BP, fecal measurements or gut microbiology.

Effects of increased wholegrain consumption on immune and inflammatory markers in healthy low habitual wholegrain consumers

Purpose Wholegrain (WG) consumption is associated with reduced risk of cardiovascular disease, but clinical data on inflammation and immune function is either conflicting or limited. The objective of this study was to assess the impact of increasing WG consumption to at least 80 g/d on markers of inflammation and glucose metabolism and on phenotypic and functional aspects of the immune system, in healthy, middle-aged adults with low habitual WG intake. Methods Subjects consumed a diet high in WG (> 80 g/d) or low in WG (< 16 g/d, refined grain diet) in a crossover study, with 6-week intervention periods, separated by a 4-week washout. Adherence to the dietary regimes was achieved by dietary advice and provision of a range of food products, with compliance verified through analysis of plasma alkylresorcinols (ARs). Results On the WG intervention, WG consumption reached 168 g/d (P < 0.001), accompanied by an increase in plasma ARs (P < 0.001) and fibre intake (P < 0.001), without affecting other aspects of dietary intake. On the WG arm there were trends for lower ex vivo activation of CD4+ T cells and circulating concentrations of IL-10, C-reactive protein, C-peptide, insulin and plasminogen activator inhibitor-1. The percentage of CD4+ central memory T cells and circulating levels of adipsin tended to increase during the WG intervention. Conclusions Despite the dramatic increase in WG consumption, there were no effects on phenotypic or functional immune parameters, markers of inflammation or metabolic markers.

Atmospheric rivers do not explain UK summer extreme rainfall

Extreme rainfall events continue to be one of the largest natural hazards in the UK. In winter, heavy precipitation and floods have been linked with intense moisture transport events associated with atmospheric rivers (ARs), yet no large-scale atmospheric precursors have been linked to summer flooding in the UK. This study investigates the link between ARs and extreme rainfall from two perspectives: 1) Given an extreme rainfall event, is there an associated AR? 2) Given an AR, is there an associated extreme rainfall event? We identify extreme rainfall events using the UK Met Office daily rain-gauge dataset and link these to ARs using two different horizontal resolution atmospheric datasets (ERA-Interim and 20th Century Re-analysis). The results show that less than 35% of winter ARs and less than 15% of summer ARs are associated with an extreme rainfall event. Consistent with previous studies, at least 50% of extreme winter rainfall events are associated with an AR. However, less than 20% of the identified summer extreme rainfall events are associated with an AR. The dependence of the water vapor transport intensity threshold used to define an AR on the years included in the study, and on the length of the season, is also examined. Including a longer period (1900-2012) compared to previous studies (1979-2005) reduces the water vapor transport intensity threshold used to define an AR.

Oxidative stress and growth-regulating intracellular signaling pathways in cardiac myocytes

The toxic effects of oxidative stress on cells (including cardiac myocytes, the contractile cells of the heart) are well known. However, an increasing body of evidence has suggested that increased production of reactive oxygen species (ROS) promotes cardiac myocyte growth. Thus, ROS may be 'second messenger' molecules in their own right, and growth-promoting neurohumoral agonists might exert their effects by stimulating production of ROS. The authors review the principal growth-promoting intracellular signaling pathways that are activated by ROS in cardiac myocytes, namely the mitogen-activated protein kinase cascades (extracellular signal-regulated kinases 1/2, c-Jun N-terminal kinases, and p38-mitogen-activated protein kinases) and the phosphoinositide 3-kinase/protein kinase B (Akt) pathway. Possible mechanisms are discussed by which these pathways are activated by ROS, including the oxidation of active site cysteinyl residues of protein and lipid phosphatases with their consequent inactivation, the potential involvement of protein kinase C or the apoptosis signal-regulating kinase 1, and the current models for the activation of the guanine nucleotide binding protein Ras.

LIMITS OF TILTING MODULES

We study the problem of when a direct limit of tilting modules is still a tilting module.

Surface-enhanced Raman scattering study of alizarin red S

This paper presents the application of surface-enhanced resonance Raman spectroscopy (SERRS) for the structural study of alizarin red S (ARS) and the nature of its interaction with silver nanoparticles. SERRS data for ARS over nanostructured silver electrodes suggest a surface-induced reaction of the adsorbed dye and the formation of an ion stabilized by the dye and alkali ions adsorbed at the metal surface. We found that precoating the SERS active substrate with 1-propanethiol inhibits the surface-induced modification of ARS. In addition to preventing structural modifications of ARS, the coating also concentrates the hydrophobic dye close enough to the SERS active interface enabling the observation of excellent Raman spectra of ARS in aqueous environment at ppm levels. The influence of resonance Raman effect and of the pH on the SERS spectra of ARS was also investigated. (C) 2010 Elsevier B.V. All rights reserved.

Comparing value-at-risk methodologies

In this paper, we compare four different Value-at-Risk (V aR) methodologies through Monte Carlo experiments. Our results indicate that the method based on quantile regression with ARCH effect dominates other methods that require distributional assumption. In particular, we show that the non-robust methodologies have higher probability to predict V aRs with too many violations. We illustrate our findings with an empirical exercise in which we estimate V aR for returns of S˜ao Paulo stock exchange index, IBOVESPA, during periods of market turmoil. Our results indicate that the robust method based on quantile regression presents the least number of violations.

Estudo comparativo da reprodutibilidade de medidas cefalométricas realizadas por radiologistas odontológicos e clínicas de radiologia

A análise cefalométrica é utilizada pelos cirurgiões-dentistas como auxiliar no diagnóstico, planejamento e acompanhamento do tratamento de seus pacientes ortodônticos, cirúrgicos e ortopédicos. No entanto, não é uma ferramenta tão precisa, pois erros significantes estão presentes nas medidas obtidas pelo mesmo ou diferentes examinadores. Assim, faz-se necessário um maior controle dos erros implicados na identificação dos pontos cefalométricos. O objetivo deste estudo foi avaliar a reprodutibilidade de medidas cefalométricas obtidas de cefalogramas realizados por três especialistas em radiologia e compará-la aos resultados obtidos por três clínicas de radiologia odontológica. Para tanto, os examinadores realizaram cefalogramas de 39 telerradiografias pertencentes à amostra de Silveira, 2003. Através do teste ANOVA, verificou-se reprodutibilidade para 17 dos 32 valores dos fatores cefalométricos analisados, o que corresponde a uma concordância em 53,1% dos fatores, enquanto as clínicas de radiologia concordaram em apenas 12,5% destes. A partir dos resultados encontrados, concluiu-se que os três especialistas em radiologia apresentaram maior reprodutibilidade nos traçados cefalométricos do que as clínicas de radiologia estudadas.