Pharmacometabonomic characterization of xenobiotic and endogenous metabolic phenotypes that account for inter-individual variation in isoniazid-induced toxicological response

An NMR-based pharmacometabonomic approach was applied to investigate inter-animal variation in response to isoniazid (INH; 200 and 400 mg/kg) in male Sprague-Dawley rats, alongside complementary clinical chemistry and histopathological analysis. Marked inter-animal variability in central nervous system (CNS) toxicity was identified following administration of a high dose of INH, which enabled characterization of CNS responders and CNS non-responders. High-resolution post-dose urinary (1)H NMR spectra were modeled both by their xenobiotic and endogenous metabolic information sets, enabling simultaneous identification of the differential metabolic fate of INH and its associated endogenous metabolic consequences in CNS responders and CNS non-responders. A characteristic xenobiotic metabolic profile was observed for CNS responders, which revealed higher urinary levels of pyruvate isonicotinylhydrazone and β-glucosyl isonicotinylhydrazide and lower levels of acetylisoniazid compared to CNS non-responders. This suggested that the capacity for acetylation of INH was lower in CNS responders, leading to increased metabolism via conjugation with pyruvate and glucose. In addition, the endogenous metabolic profile of CNS responders revealed higher urinary levels of lactate and glucose, in comparison to CNS non-responders. Pharmacometabonomic analysis of the pre-dose (1)H NMR urinary spectra identified a metabolic signature that correlated with the development of INH-induced adverse CNS effects and may represent a means of predicting adverse events and acetylation capacity when challenged with high dose INH. Given the widespread use of INH for the treatment of tuberculosis, this pharmacometabonomic screening approach may have translational potential for patient stratification to minimize adverse events.

Beta event-related desynchronization as an index of individual differences in processing human facial expression: further investigations of autistic traits in typically developing adults

The human mirror neuron system (hMNS) has been associated with various forms of social cognition and affective processing including vicarious experience. It has also been proposed that a faulty hMNS may underlie some of the deficits seen in the autism spectrum disorders (ASDs). In the present study we set out to investigate whether emotional facial expressions could modulate a putative EEG index of hMNS activation (mu suppression) and if so, would this differ according to the individual level of autistic traits [high versus low Autism Spectrum Quotient (AQ) score]. Participants were presented with 3 s films of actors opening and closing their hands (classic hMNS mu-suppression protocol) while simultaneously wearing happy, angry, or neutral expressions. Mu-suppression was measured in the alpha and low beta bands. The low AQ group displayed greater low beta event-related desynchronization (ERD) to both angry and neutral expressions. The high AQ group displayed greater low beta ERD to angry than to happy expressions. There was also significantly more low beta ERD to happy faces for the low than for the high AQ group. In conclusion, an interesting interaction between AQ group and emotional expression revealed that hMNS activation can be modulated by emotional facial expressions and that this is differentiated according to individual differences in the level of autistic traits. The EEG index of hMNS activation (mu suppression) seems to be a sensitive measure of the variability in facial processing in typically developing individuals with high and low self-reported traits of autism.

Global to city scale urban anthropogenic heat flux: model and variability

The large scale urban consumption of energy (LUCY) model simulates all components of anthropogenic heat flux (QF) from the global to individual city scale at 2.5 × 2.5 arc-minute resolution. This includes a database of different working patterns and public holidays, vehicle use and energy consumption in each country. The databases can be edited to include specific diurnal and seasonal vehicle and energy consumption patterns, local holidays and flows of people within a city. If better information about individual cities is available within this (open-source) database, then the accuracy of this model can only improve, to provide the community data from global-scale climate modelling or the individual city scale in the future. The results show that QF varied widely through the year, through the day, between countries and urban areas. An assessment of the heat emissions estimated revealed that they are reasonably close to those produced by a global model and a number of small-scale city models, so results from LUCY can be used with a degree of confidence. From LUCY, the global mean urban QF has a diurnal range of 0.7–3.6 W m−2, and is greater on weekdays than weekends. The heat release from building is the largest contributor (89–96%), to heat emissions globally. Differences between months are greatest in the middle of the day (up to 1 W m−2 at 1 pm). December to February, the coldest months in the Northern Hemisphere, have the highest heat emissions. July and August are at the higher end. The least QF is emitted in May. The highest individual grid cell heat fluxes in urban areas were located in New York (577), Paris (261.5), Tokyo (178), San Francisco (173.6), Vancouver (119) and London (106.7). Copyright © 2010 Royal Meteorological Society

Individual differences and the role of the L1 in L2 processing: an ERP investigation

This study used ERP (event-related potentials) to examine both the role of the L1 and the role of individual differences in the processing of agreement violations. Theories of L2 acquisition differ with regard to whether or not native-like acquisition of L2 features is possible (Schwartz and Sprouse, 1994, 1996; Tsimpli and Mastropavlou, 2007), and the results of previous ERP studies are inconsistent when it comes to whether or not native-like processing is observed in response to L2 agreement violations (e.g., Sabourin, 2003; Tokowicz and MacWhinney, 2005). Furthermore, studies of learners in early stages of L2 acquisition have found variability in the emergence of native-like responses (e.g., McLaughlin et al., 2010; Tanner et al., 2009), but sources of variability have not been investigated. The current study examines responses to gender and number agreement violations in English-speaking learners of Spanish (n=24). Stimuli targeted agreement in three conditions: subject-verb agreement (el barco flota/*flotan), which is similar in Spanish and English; number agreement on adjectival predicates (la isla rocosa/*rocosas), a context in which agreement is not instantiated in English; and gender agreement on adjectival predicates (la isla rocosa/*rocoso), which is unique to Spanish. Grammaticality judgments and ERP responses were also tested for correlations with aptitude scores on the Modern Languages Aptitude Test (MLAT; Carroll and Sapon, 1959) and the Raven Advanced Progressive Matrices (Raven, 1965). Results are in line with theories that claim native-like processing is acquirable, since learners demonstrated similar ERP responses to a control group of native Spanish-speakers (n=8) with regard to all three agreement types. Additionally, the MLAT (but not the Raven) was significantly correlated with sensitivity to number violations, both in terms of grammaticality judgments and ERP amplitudes, indicating a role for verbal but not nonverbal aptitude in L2 processing.

Investigation of the accuracy of historical irradiance products and interannual variability of solar irradiance using Met Office ground data

Met Office station data from 1980 to 2012 has been used to characterise the interannual variability of incident solar irradiance across the UK. The same data are used to evaluate four popular historical irradiance products to determine which are most suitable for use by the UK PV industry for site selection and system design. The study confirmed previous findings that interannual variability is typically 3–6% and weighted average probability of a particular percentage deviation from the mean at an average site in the UK was calculated. This weighted average showed that fewer than 2% of site-years could be expected to fall below 90% of the long-term site mean. The historical irradiance products were compared against Met Office station data from the input years of each product. This investigation has found that all products perform well. No products have a strong spatial trend. Meteonorm 7 is most conservative (MBE = −2.5%), CMSAF is most optimistic (MBE = +3.4%) and an average of all four products performs better than any one individual product (MBE = 0.3%)

Variability and trends in England and Wales precipitation

The England and Wales precipitation (EWP) dataset is a homogeneous time series of daily accumulations from 1931 to 2014, composed from rain gauge observations spanning the region. The daily regional-average precipitation statistics are shown to be well described by a Weibull distribution, which is used to define extremes in terms of percentiles. Computed trends in annual and seasonal precipitation are sensitive to the period chosen, due to large variability on interannual and decadal timescales. Atmospheric circulation patterns associated with seasonal precipitation variability are identified. These patterns project onto known leading modes of variability, all of which involve displacements of the jet stream and storm-track over the eastern Atlantic. The intensity of daily precipitation for each calendar season is investigated by partitioning all observations into eight intensity categories contributing equally to the total precipitation in the dataset. Contrary to previous results based on shorter periods, no significant trends of the most intense categories are found between 1931 and 2014. The regional-average precipitation is found to share statistical properties common to the majority of individual stations across England and Wales used in previous studies. Statistics of the EWP data are examined for multi-day accumulations up to 10 days, which are more relevant for river flooding. Four recent years (2000, 2007, 2008 and 2012) have a greater number of extreme events in the 3-and 5-day accumulations than any previous year in the record. It is the duration of precipitation events in these years that is remarkable, rather than the magnitude of the daily accumulations.

Large variability of proanthocyanidin content and composition in sainfoin (onobrychis viciifolia)

Proanthocyanidins (PAs) in sainfoin (Onobrychis viciifolia Scop.) are of interest to ameliorate the sustainability of livestock production. However, sainfoin forage yield and PA concentrations, as well as their composition, require optimization. Individual plants of 27 sainfoin accessions from four continents were analyzed with LC-ESI-QqQ-MS/MS for PA concentrations and simple phenolic compounds. Large variability existed in PA concentrations (23.0–47.5 mg g–1 leaf dry matter (DM)), share of prodelphinidins (79–96%), and mean degree of polymerization (11–14) among, but also within, accessions. PAs were mainly located in leaves (26.8 mg g–1 DM), whereas stems had less PAs (7.8 mg g–1 DM). Overall, high-yielding plants had lower PA leaf concentrations (R2 = 0.16, P < 0.001) and fewer leaves (R2 = 0.66, P < 0.001). However, the results show that these two trade-offs between yield and bioactive PAs can be overcome.

Interannual-decadal variability of wintertime mixed layer depths in the North Pacific detected by an ensemble of ocean syntheses

The interannual-decadal variability of the wintertime mixed layer depths (MLDs) over the North Pacific is investigated from an empirical orthogonal function (EOF) analysis of an ensemble of global ocean reanalyses. The first leading EOF mode represents the interannual MLD anomalies centered in the eastern part of the central mode water formation region in phase opposition with those in the eastern subtropics and the central Alaskan Gyre. This first EOF mode is highly correlated with the Pacific decadal oscillation index on both the interannual and decadal time scales. The second leading EOF mode represents the MLD variability in the subtropical mode water (STMW) formation region and has a good correlation with the wintertime West Pacific (WP) index with time lag of 3 years, suggesting the importance of the oceanic dynamical response to the change in the surface wind field associated with the meridional shifts of the Aleutian Low. The above MLD variabilities are in basic agreement with previous observational and modeling findings. Moreover the reanalysis ensemble provides uncertainty estimates. The interannual MLD anomalies in the first and second EOF modes are consistently represented by the individual reanalyses and the amplitudes of the variabilities generally exceed the ensemble spread of the reanalyses. Besides, the resulting MLD variability indices, spanning the 1948–2012 period, should be helpful for characterizing the North Pacific climate variability. In particular, a 6-year oscillation including the WP teleconnection pattern in the atmosphere and the oceanic MLD variability in the STMW formation region is first detected.

Fast and slow precipitation responses to individual climate forcers: a PDRMIP multi-model study

Precipitation is expected to respond differently to various drivers of anthropogenic climate change. We present the first results from the Precipitation Driver and Response Model Intercomparison Project (PDRMIP), where nine global climate models have perturbed CO2, CH4, black carbon, sulfate, and solar insolation. We divide the resulting changes to global mean and regional precipitation into fast responses that scale with changes in atmospheric absorption and slow responses scaling with surface temperature change. While the overall features are broadly similar between models, we find significant regional intermodel variability, especially over land. Black carbon stands out as a component that may cause significant model diversity in predicted precipitation change. Processes linked to atmospheric absorption are less consistently modeled than those linked to top-of-atmosphere radiative forcing. We identify a number of land regions where the model ensemble consistently predicts that fast precipitation responses to climate perturbations dominate over the slow, temperature-driven responses.

Caracterização dos resíduos esgotados de sistemas de tratamento individual de esgotos de Natal

In Natal still dominates the use of individual disposal systems for domestic sewage, once only 29% of the city has a sewarage system. Wastes that are accumulated in these individual treatment systems should be exhausted periodically, service provided by collector entrepreneurs. Some of these companies causing major damage to the environment. In Natal, only two companies have their own septage (RESTI) treatment system, which were designed with parameters from domestic sewage generating strain and inefficient systems. Therefore, the characterization becomes essential as a source of parameters for their design. Thus, this work presents the physical-chemical and microbiological characterization of waste pumped from individual sewage treatment systems. Samples collections were made weekly from 5 different trucks at the reception point on the treatment plant on the point of the preliminary treatment. From each truck it was taken 5 samples during the discharge in order to make a composite sample. Afterwards, samples were carried out to laboratory and analyses for determination of temperature, pH, conductivity, BOD, COD, nitrogen (ammonia e organic), alkalinity, oils, phosphorus, solids, faecal coliforms and helminth egg. The results were treated as a single database, and ranked according to its generating source (multi and single house, lodging, health, services and / or food), area of origin (metropolitan, south and north) and type of system (cesspits, septic tank and / or sink). Through these data it was possible to verify that the type of system adopted by most in Natal and the metropolitan region is cesspit, besides to confirm the difference between the septage of areas with a population have different social and economical characteristics. It was found that the septage have higher concentrations than domestic sewage, except for thermotolerant coliforms that showed concentrations of 1,38E+07. Among the parameters studied, is the median values identified for COD (3,549 mg / L), BOD (973mg / L) and total solids (3.557mg / L). The volatile fraction constitutes about 70% of the total solids of the septage. For helminths has been a median of 7 eggs/L. In general, the characteristics of the waste followed the variability found in the literature reviewed for all variables, showing high amplitudes

Comparison of the Polar S810i monitor and the ECG for the analysis of heart rate variability in the time and frequency domains

The aim of the present study was to compare heart rate variability (HRV) at rest and during exercise using a temporal series obtained with the Polar S810i monitor and a signal from a LYNX® signal conditioner (BIO EMG 1000 model) with a channel configured for the acquisition of ECG signals. Fifteen healthy subjects aged 20.9 ± 1.4 years were analyzed. The subjects remained at rest for 20 min and performed exercise for another 20 min with the workload selected to achieve 60% of submaximal heart rate. RR series were obtained for each individual with a Polar S810i instrument and with an ECG analyzed with a biological signal conditioner. The HRV indices (rMSSD, pNN50, LFnu, HFnu, and LF/HF) were calculated after signal processing and analysis. The unpaired Student t-test and intraclass correlation coefficient were used for data analysis. No statistically significant differences were observed when comparing the values analyzed by means of the two devices for HRV at rest and during exercise. The intraclass correlation coefficient demonstrated satisfactory correlation between the values obtained by the devices at rest (pNN50 = 0.994; rMSSD = 0.995; LFnu = 0.978; HFnu = 0.978; LF/HF = 0.982) and during exercise (pNN50 = 0.869; rMSSD = 0.929; LFnu = 0.973; HFnu = 0.973; LF/HF = 0.942). The calculation of HRV values by means of temporal series obtained from the Polar S810i instrument appears to be as reliable as those obtained by processing the ECG signal captured with a signal conditioner.

Chromosomes of Theridiidae spiders (Entelegynae): interspecific karyotype diversity in Argyrodes and diploid number intraspecific variability in Nesticodes rufipes

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Uncertainties in the prediction of spatial variability of soil CO2 emissions and related properties

A emissão de CO2 do solo apresenta alta variabilidade espacial, devido à grande dependência espacial observada nas propriedades do solo que a influenciam. Neste estudo, objetivou-se: caracterizar e relacionar a variabilidade espacial da respiração do solo e propriedades relacionadas; avaliar a acurácia dos resultados fornecidos pelo método da krigagem ordinária e simulação sequencial gaussiana; e avaliar a incerteza na predição da variabilidade espacial da emissão de CO2 do solo e demais propriedades utilizando a simulação sequencial gaussiana. O estudo foi conduzido em uma malha amostral irregular com 141 pontos, instalada sobre a cultura de cana-de-açúcar. Nesses pontos foram avaliados a emissão de CO2 do solo, a temperatura do solo, a porosidade livre de água, o teor de matéria orgânica e a densidade do solo. Todas as variáveis apresentaram estrutura de dependência espacial. A emissão de CO2 do solo mostrou correlações positivas com a matéria orgânica (r = 0,25, p < 0,05) e a porosidade livre de água (r = 0,27, p <0,01) e negativa com a densidade do solo (r = -0,41, p < 0,01). No entanto, quando os valores estimados espacialmente (N=8833) são considerados, a porosidade livre de água passa a ser a principal variável responsável pelas características espaciais da respiração do solo, apresentando correlação de 0,26 (p < 0,01). As simulações individuais propiciaram, para todas as variáveis analisadas, melhor reprodução das funções de distribuição acumuladas e dos variogramas, em comparação à krigagem e estimativa E-type. As maiores incertezas na predição da emissão de CO2 estiveram associadas às regiões da área estudada com maiores valores observados e estimados, produzindo estimativas, ao longo do período estudado, de 0,18 a 1,85 t CO2 ha-1, dependendo dos diferentes cenários simulados. O conhecimento das incertezas gerado por meio dos diferentes cenários de estimativa pode ser incluído em inventários de gases do efeito estufa, resultando em estimativas mais conservadoras do potencial de emissão desses gases.

Population structure and genetic variability in the Murrah dairy breed of water buffalo in Brazil accessed via pedigree analysis

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Seleção individual com teste de progênies em crambe (Crambe abyssinica Hochst)

Pós-graduação em Agronomia (Agricultura) - FCA