Structurally-related (−)-epicatechin metabolites in humans: assessment using de novo chemically synthesized authentic standards

Accumulating data suggest that diets rich in flavanols and procyanidins are beneficial for human health. In this context, there has been a great interest in elucidating the systemic levels and metabolic profiles at which these compounds occur in humans. While recent progress has been made, there still exist considerable differences and various disagreements with regard to the mammalian metabolites of these compounds, which in turn is largely a consequence of the lack of availability of authentic standards that would allow for the directed development and validation of expedient analytical methodologies. In the present study, we developed a method for the analysis of structurally-related flavanol metabolites using a wide range of authentic standards. Applying this method in the context of a human dietary intervention study using comprehensively characterized and standardized flavanol- and procyanidin-containing cocoa, we were able to identify the structurally-related (−)-epicatechin metabolites (SREM) postprandially extant in the systemic circulation of humans. Our results demonstrate that (−)-epicatechin-3′-β-D-glucuronide, (−)-epicatechin-3′-sulfate, and a 3′-O-methyl(−)-epicatechin-5/7-sulfate are the predominant SREM in humans, and further confirm the relevance of the stereochemical configuration in the context of flavanol metabolism. In addition, we also identified plausible causes for the previously reported discrepancies regarding flavanol metabolism, consisting to a significant extent of inter-laboratory differences in sample preparation (enzymatic treatment and sample conditioning for HPLC analysis) and detection systems. Thus, these findings may also aid in the establishment of consensus on this topic.

Gut microbial catabolism of grape seed flavan-3-ols by human faecal microbiota. Targetted analysis of precursor compounds, intermediate metabolites and end-products.

In vitro batch culture fermentations were conducted with grape seed polyphenols and human faecal microbiota, in order to monitor both changes in precursor flavan-3-ols and the formation of microbial-derived metabolites. By the application of UPLC-DAD-ESI-TQ MS, monomers, and dimeric and trimeric procyanidins were shown to be degraded during the first 10 h of fermentation, with notable inter-individual differences being observed between fermentations. This period (10 h) also coincided with the maximum formation of intermediate metabolites, such as 5-(3′,4′-dihydroxyphenyl)-γ-valerolactone and 4-hydroxy-5-(3′,4′-dihydroxyphenyl)-valeric acid, and of several phenolic acids, including 3-(3,4-dihydroxyphenyl)-propionic acid, 3,4-dihydroxyphenylacetic acid, 4-hydroxymandelic acid, and gallic acid (5–10 h maximum formation). Later phases of the incubations (10–48 h) were characterised by the appearance of mono- and non-hydroxylated forms of previous metabolites by dehydroxylation reactions. Of particular interest was the detection of γ-valerolactone, which was seen for the first time as a metabolite from the microbial catabolism of flavan-3-ols. Changes registered during fermentation were finally summarised by a principal component analysis (PCA). Results revealed that 5-(3′,4′-dihydroxyphenyl)-γ-valerolactone was a key metabolite in explaining inter-individual differences and delineating the rate and extent of the microbial catabolism of flavan-3-ols, which could finally affect absorption and bioactivity of these compounds.

Neural correlates of true and false memory in mild cognitive impairment

The goal of this research was to investigate the changes in neural processing in mild cognitive impairment. We measured phase synchrony, amplitudes, and event-related potentials in veridical and false memory to determine whether these differed in participants with mild cognitive impairment compared with typical, age-matched controls. Empirical mode decomposition phase locking analysis was used to assess synchrony, which is the first time this analysis technique has been applied in a complex cognitive task such as memory processing. The technique allowed assessment of changes in frontal and parietal cortex connectivity over time during a memory task, without a priori selection of frequency ranges, which has been shown previously to influence synchrony detection. Phase synchrony differed significantly in its timing and degree between participant groups in the theta and alpha frequency ranges. Timing differences suggested greater dependence on gist memory in the presence of mild cognitive impairment. The group with mild cognitive impairment had significantly more frontal theta phase locking than the controls in the absence of a significant behavioural difference in the task, providing new evidence for compensatory processing in the former group. Both groups showed greater frontal phase locking during false than true memory, suggesting increased searching when no actual memory trace was found. Significant inter-group differences in frontal alpha phase locking provided support for a role for lower and upper alpha oscillations in memory processing. Finally, fronto-parietal interaction was significantly reduced in the group with mild cognitive impairment, supporting the notion that mild cognitive impairment could represent an early stage in Alzheimer’s disease, which has been described as a ‘disconnection syndrome’.

The APE atlas

This Atlas presents statistical analyses of the simulations submitted to the Aqua-Planet Experiment (APE) data archive. The simulations are from global Atmospheric General Circulation Models (AGCM) applied to a water-covered earth. The AGCMs include ones actively used or being developed for numerical weather prediction or climate research. Some are mature, application models and others are more novel and thus less well tested in Earth-like applications. The experiment applies AGCMs with their complete parameterization package to an idealization of the planet Earth which has a greatly simplified lower boundary that consists of an ocean only. It has no land and its associated orography, and no sea ice. The ocean is represented by Sea Surface Temperatures (SST) which are specified everywhere with simple, idealized distributions. Thus in the hierarchy of tests available for AGCMs, APE falls between tests with simplified forcings such as those proposed by Held and Suarez (1994) and Boer and Denis (1997) and Earth-like simulations of the Atmospheric Modeling Intercomparison Project (AMIP, Gates et al., 1999). Blackburn and Hoskins (2013) summarize the APE and its aims. They discuss where the APE fits within a modeling hierarchy which has evolved to evaluate complete models and which provides a link between realistic simulation and conceptual models of atmospheric phenomena. The APE bridges a gap in the existing hierarchy. The goals of APE are to provide a benchmark of current model behaviors and to stimulate research to understand the cause of inter-model differences., APE is sponsored by the World Meteorological Organization (WMO) joint Commission on Atmospheric Science (CAS), World Climate Research Program (WCRP) Working Group on Numerical Experimentation (WGNE). Chapter 2 of this Atlas provides an overview of the specification of the eight APE experiments and of the data collected. Chapter 3 lists the participating models and includes brief descriptions of each. Chapters 4 through 7 present a wide variety of statistics from the 14 participating models for the eight different experiments. Additional intercomparison figures created by Dr. Yukiko Yamada in AGU group are available at http://www.gfd-dennou.org/library/ape/comparison/. This Atlas is intended to present and compare the statistics of the APE simulations but does not contain a discussion of interpretive analyses. Such analyses are left for journal papers such as those included in the Special Issue of the Journal of the Meteorological Society of Japan (2013, Vol. 91A) devoted to the APE. Two papers in that collection provide an overview of the simulations. One (Blackburn et al., 2013) concentrates on the CONTROL simulation and the other (Williamson et al., 2013) on the response to changes in the meridional SST profile. Additional papers provide more detailed analysis of the basic simulations, while others describe various sensitivities and applications. The APE experiment data base holds a wealth of data that is now publicly available from the APE web site: http://climate.ncas.ac.uk/ape/. We hope that this Atlas will stimulate future analyses and investigations to understand the large variation seen in the model behaviors.

The water balance of northern Africa during the mid-Holocene: an evaluation of the 6ka BP PMIP simulations

Runoff fields over northern Africa (10–25°N, 20°W–30°E) derived from 17 atmospheric general circulation models driven by identical 6 ka BP orbital forcing, sea surface temperatures, and CO2 concentration have been analyzed using a hydrological routing scheme (HYDRA) to simulate changes in lake area. The AGCM-simulated runoff produced six-fold differences in simulated lake area between models, although even the largest simulated changes considerably underestimate the observed changes in lake area during the mid-Holocene. The inter-model differences in simulated lake area are largely due to differences in simulated runoff (the squared correlation coefficient, R2, is 0.84). Most of these differences can be attributed to differences in the simulated precipitation (R2=0.83). The higher correlation between runoff and simulated lake area (R2=0.92) implies that simulated differences in evaporation have a contributory effect. When runoff is calculated using an offline land-surface scheme (BIOME3), the correlation between runoff and simulated lake area is (R2=0.94). Finally, the spatial distribution of simulated precipitation can exert an important control on the overall response.

Ocean heat uptake processes: a model intercomparison

We compare the quasi-equilibrium heat balances, as well as their responses to 4×CO2 perturbation, among three global climate models with the aim to identify and explain inter-model differences in ocean heat uptake (OHU) processes. We find that, in quasi-equilibrium, convective and mixed layer processes, as well as eddy-related processes, cause cooling of the subsurface ocean. The cooling is balanced by warming caused by advective and diapycnally diffusive processes. We also find that in the CO2-perturbed climates the largest contribution to OHU comes from changes in vertical mixing processes and the mean circulation, particularly in the extra-tropics, caused both by changes in wind forcing, and by changes in high-latitude buoyancy forcing. There is a substantial warming in the tropics, a significant part of which occurs because of changes in horizontal advection in extra-tropics. Diapycnal diffusion makes only a weak contribution to the OHU, mainly in the tropics, due to increased stratification. There are important qualitative differences in the contribution of eddy-induced advection and isopycnal diffusion to the OHU among the models. The former is related to the different values of the coefficients used in the corresponding scheme. The latter is related to the different tapering formulations of the isopycnal diffusion scheme. These differences affect the OHU in the deep ocean, which is substantial in two of the models, the dominant region of deep warming being the Southern Ocean. However, most of the OHU takes place above 2000 m, and the three models are quantitatively similar in their global OHU efficiency and its breakdown among processes and as a function of latitude.

Exploration of the neural correlates of cerebral palsy for sensorimotor BCI control

Cerebral palsy (CP) includes a broad range of disorders, which can result in impairment of posture and movement control. Brain-computer interfaces (BCIs) have been proposed as assistive devices for individuals with CP. Better understanding of the neural processing underlying motor control in affected individuals could lead to more targeted BCI rehabilitation and treatment options. We have explored well-known neural correlates of movement, including event-related desynchronization (ERD), phase synchrony, and a recently-introduced measure of phase dynamics, in participants with CP and healthy control participants. Although present, significantly less ERD and phase locking were found in the group with CP. Additionally, inter-group differences in phase dynamics were also significant. Taken together these findings suggest that users with CP exhibit lower levels of motor cortex activation during motor imagery, as reflected in lower levels of ongoing mu suppression and less functional connectivity. These differences indicate that development of BCIs for individuals with CP may pose additional challenges beyond those faced in providing BCIs to healthy individuals.

Entrepreneurial activity across European cities

The importance of entrepreneurship as a driving force in the economic development has been widely recognised. Respectively, a growing number of empirical studies have focused on explaining variation in entrepreneurial activity at various spatial levels with the majority of them taking either a cross-country perspective or looking at the inter-regional differences. More recent studies on entrepreneurship have shifted their focus to examining cross-city variation in entrepreneurship. However, overall, given limited city-level data availability, scarce work has been undertaken so far on cross-city entrepreneurship within the spatially oriented entrepreneurship research. Furthermore, to our best knowledge, no empirical studies exist on entrepreneurship in European cities and our paper aims to fill this gap

Diferencial de salários e produtividade no setor de serviços brasileiro

This paper provides new information about inter-industry wage di§erentials in Brazil. Using data from the National Survey Sample of Households, we can see that from 1983 to 1995 the relative average wage of the service sector compared to the goods sector decreased, whereas from 1995 to 2007 it increased at a higher level than the previous decrease. After controlling for a variety of work characteristics, we can still see the positive evolution of rel- ative ages in the service sector. We conclude that this development has some explanations: the period of economic growth and stabilization that started after 1994 generated a positive income e§ect, and the service sector beneÖted more from it. Also, the structural transfor- mation that the developed countries already went through still hasn¥t Önished in Brazil. That probably helped improving relative wages in the service sector and it¥s expected the continuation of this process, so as the structural transformation evolves inter-industry wage di§erentials will converge.

Rent-sharing in Brazil: using trade liberalization as a natural experiment

This paper examines the extent of rent-sharing in Brazil, between 1988 and 1995, combining two different data sets: annual industrial surveys (pIA) and annual household surveys (PNADs). The aim is to use the trade liberalization policies that took place in Brazil in the early 1990s as a "natural experiment" to examine the impact ofproduct market rents on wages. We first estimate inter-industry wage differentials in Brazil, using the household surveys, afier controlling for various observable workers' characteristics. In a reduced form fixed effects equation, these controlled inter-industry differentials are seen to depend on the industries' rate of effective tariff. We also find that LSDV estimates of the effect of value-added per worker (computed using the industrial surveys) on the wage differentials are positive, but somewhat small. However, we find that instrumenting the valued-added with the effective tariffs more than doubles the estimated rent-sharing coefficient. The paper concludes that rent-sharing is prevalent in the Brazilian manufacturing sector, and this mechanism transferred part of the productivity gains due to trade liberalization to manufacturing workers in the form ofhigher (controlled) wage premium.

Effects of age and gender on upper airway, lower airway and upper lip growth

The aim of the present retrospective study was to evaluate the influence of age and gender on upper and lower airway width and upper lip length. In this study, 390 lateral cephalograms were divided into 13 age groups (ranging from 6 to 18 years) and were analyzed. The inter-group differences were analyzed using a MANOVA (Multivariate Analysis of the Variance), and the intragroup differences were analyzed using an ANOVA (Analysis of the Variance) and Tukey's test. The results of the present study indicated that although the airway width and the upper lip length increased with age, the lower airway width exhibited variable growth between the ages of six and eighteen years. The airway width was significantly greater in females than males, whereas the upper airway width was similar between these two genders. The lip length was significantly shorter in females than males. The lower airway width and upper lip length were significantly different between males and females, whereas the upper airway width was similar for the genders. The upper airway width and upper lip exhibited incremental growth between the ages of six and eighteen years. The upper lip closely followed the growth pattern of the upper airway width; the growth plateaued between the ages of 6 and 9 years, increased from 9 to 16 years and plateaued from 16 to 18 years.

The People's Republic of China and Latin America and the Caribbean: towards a strategic relationship

Includes bibliography

Forum for East Asia-Latin America Cooperation (FEALAC): new biregional trade and investment relations in a changing world economic environment$c

Includes bibliography

Latin America and Asia Pacific trade and investment relations at a time of international financial crisis

Includes Bibliography

Growth and carbon isotopes of Mediterranean trees reveal contrasting responses to increased carbon dioxide and drought

Forest dynamics will depend upon the physiological performance of individual tree species under more stressful conditions caused by climate change. In order to compare the idiosyncratic responses of Mediterranean tree species (Quercus faginea, Pinus nigra, Juniperus thurifera) coexisting in forests of central Spain, we evaluated the temporal changes in secondary growth (basal area increment; BAI) and intrinsic water-use efficiency (iWUE) during the last four decades, determined how coexisting species are responding to increases in atmospheric CO2 concentrations (Ca) and drought stress, and assessed the relationship among iWUE and growth during climatically contrasting years. All species increased their iWUE (ca. +15 to +21 %) between the 1970s and the 2000s. This increase was positively related to Ca for J. thurifera and to higher Ca and drought for Q. faginea and P. nigra. During climatically favourable years the study species either increased or maintained their growth at rising iWUE, suggesting a higher CO2 uptake. However, during unfavourable climatic years Q. faginea and especially P. nigra showed sharp declines in growth at enhanced iWUE, likely caused by a reduced stomatal conductance to save water under stressful dry conditions. In contrast, J. thurifera showed enhanced growth also during unfavourable years at increased iWUE, denoting a beneficial effect of Ca even under climatically harsh conditions. Our results reveal significant inter-specific differences in growth driven by alternative physiological responses to increasing drought stress. Thus, forest composition in the Mediterranean region might be altered due to contrasting capacities of coexisting tree species to withstand increasingly stressful conditions. © 2013 Springer-Verlag Berlin Heidelberg.