Total Blood Carbon Monoxide: Alternative to Carboxyhemoglobin as Biological Marker for Carbon Monoxide Poisoning Determination.

As one of the most abundant toxic contaminants in the atmosphere, carbon monoxide (CO) plays a significant role in toxicology and public health. Every year, around half of the accidental non-fire-related poisoning deaths are attributed to CO in the USA, UK and many other countries. However, due to the non-specificity of the symptoms and often encountered inconsistency of these with the results obtained from measurements of the biomarker for CO poisonings, carboxyhemoglobin (COHb), there is a high rate of misdiagnoses. The mechanism of toxicity of CO includes not only the reduced transport of oxygen caused by COHb but also the impairment of cellular respiration and activation of oxidative metabolism by binding to other proteins. Therefore, in this study we propose the measurement of the total amount of CO in blood (TBCO) by airtight gas syringe-gas chromatography-mass spectrometry (AGS-GC-MS) as an alternative to COHb for the determination of CO exposures. The method is validated for a clinical range with TBCO concentrations of 1.63-104 nmol/mL of headspace (HS) (0.65-41.6 μmol/mL blood). The limit of quantification was found between 2 and 5 nmol/mL HS (0.8 and 2 μmol/mL blood). The method is applied to a cohort of 13 patients, who were exposed to CO under controlled conditions, and the results are compared to those obtained by CO-oximetry. Furthermore, samples were compared before and after a "flushing" step to remove excess CO. Results showed a significant decrease in TBCO when samples were flushed (10-60%), whereas no constant trend was observed for COHb. Therefore, measurement of TBCO by AGS-GC-MS suggests the presence of more dissolved CO than previously known. This constitutes a first step into the acknowledgment of a possibly significant amount of CO present not in the form of COHb, but as free CO, which might help explain the incongruences with symptoms and decrease misdiagnoses

Carbon monoxide analysis method in human blood by Airtight Gas Syringe - Gas Chromatography - Mass Spectrometry (AGS-GC-MS): Relevance for postmortem poisoning diagnosis.

Carbon monoxide is one of the most abundant toxic air pollutants. Symptoms of a CO intoxication are non-specific, leading to a high number of misdiagnosed CO poisoning cases that are missing in the disease statistics. The chemical nature of the molecule makes it difficult to detect for long periods and at low levels, thus requiring a very accurate and sensitive method. Current methods capable of accurate and sensitive analyses are available, however an inconsistency between results and symptoms are frequently reported. Therefore, an improved method for the analysis of carbon monoxide in blood and in the headspace (HS) of the sampling tube with the use of Airtight Gas Syringe - Gas Chromatography - Mass Spectrometry (AGS-GC-MS) is hereby presented and validated, for CO concentrations in a range of 10-200 nmol/mL HS (2-40 μmol/mL blood). Analytical LOQ is found at 0.9 nmol/mL HS (0.18 μmol/mL blood) and LOD at 0.1 nmol/mL gas. Application to intoxicated samples from autopsies and comparison to previously published methods show that this method is more appropriate, since performed under fully controlled conditions. Results show higher CO concentrations compared to previous approaches, indicating that results might have been underestimating the true blood CO burden. Therefore, this approach has the potential to help reduce the misdiagnosed cases and the gap between measurement and diagnosis of CO poisonings

Inhibition of cell proliferation, migration and invasion of B16-F10 melanoma cells by α-mangostin

In this study, we have evaluated the potential antineoplastic effects of α-mangostin (α-M), the most representative xanthone in Garcinia mangostana pericarp, on melanoma cell lines. This xanthone markedly inhibits the proliferation of high-metastatic B16-F10 melanoma cells. Furthermore, by deeply analyzing which steps in the metastatic process are influenced by xanthone it was observed that α-M strongly interferes with homotypic aggregation, adhesion, plasticity and invasion ability of B16-F10 cells, probably by the observed reduction of metalloproteinase-9 activity. The antiproliferative and antimetastatic properties of α-M have been established in human SK-MEL-28 and A375 melanoma cells. In order to identify pathways potentially involved in the antineoplastic properties of α-M, a comparative mass spectrometry proteomic approach was employed. These findings may improve our understanding of the molecular mechanisms underlying the anti-cancer effects of α-M on melanoma

The spermidine analogue GC7 (N1-guanyl-1,7-diamineoheptane) induces autophagy through a mechanism not involving the hypusination of eIF5A

The exogenous administration of spermidine promotes longevity in many model organisms. It has been proposed that this anti-age activity of spermidine is related to this polyamine's ability to promote autophagy. Since spermidine is the substrate for the eIF5A post-translational modification by hypusination, we asked ourselves whether mature eIF5A may represent the link between spermidine and autophagy induction. To test this hypothesis, we inhibited the conversion of native eIF5A by a pharmacological approach, using the N1-guanyl-1,7-diamineoheptane (GC7), a spermidine analogue which competitively and reversibly inhibits deoxyhypusine synthase (DHS). In addition, we also employed genetic approaches by ablating both the eIF5A protein itself and DHS, the rate limiting enzyme catalyzing the conversion of lysine to hypusine. Collectively the data presented in this study demonstrate that the mature eIF5A (hypusinated form) is not involved in the autophagic pathway and that the inhibitor of DHS, GC7, produces off-target effect(s) resulting in marked induction of basal autophagy. These data are relevant in light of the fact that GC7 is considered a potent and selective inhibitor of DHS and is a potential candidate drug for cancer, diabetes and HIV therapy

Antarctic food web architecture under varying dynamics of sea ice cover

open7noIn the Ross Sea, biodiversity organisation is strongly influenced by sea-ice cover, which is characterised by marked spatio-temporal variations. Expected changes in seasonal sea-ice dynamics will be reflected in food web architecture, providing a unique opportunity to study effects of climate change. Based on individual stable isotope analyses and the high taxonomic resolution of sampled specimens, we described benthic food webs in contrasting conditions of seasonal sea-ice persistence (early vs. late sea-ice break up) in medium-depth waters in Terra Nova Bay (Ross Sea). The architecture of biodiversity was reshaped by the pulsed input of sympagic food sources following sea-ice break up, with food web simplification, decreased intraguild predation, potential disturbance propagation and increased vulnerability to biodiversity loss. Following our approach, it was possible to describe in unprecedented detail the complex structure of biodiverse communities, emphasising the role of sympagic inputs, regulated by sea-ice dynamics, in structuring Antarctic medium-depth benthic food webs.openRossi L.; Sporta Caputi S.; Calizza E.; Careddu G.; Oliverio M.; Schiaparelli S.; Costantini M.L.Rossi, L.; Sporta Caputi, S.; Calizza, E.; Careddu, G.; Oliverio, M.; Schiaparelli, S.; Costantini, M. L

High genetic connectivity in a gastropod with long-lived planktonic larvae

Genetic connectivity plays a crucial role in shaping the geographic structure of species. Our aim in this study was to explore the pattern of genetic connectivity in Bursa scrobilator, an iconic marine caenogastropod with long-lived pelagic larvae. Our study was based on the analysis of DNA sequence data for the 658-bp barcoding fragment of the mitochondrial cytochrome c oxidase subunit I (COI) gene. This is the largest DNA sequence dataset assembled to date for B. scrobilator. These data confirm that the two recently described subspecies B. scrobilator scrobilator (Linnaeus, 1758), from the Mediterranean and Macaronesia, and B. s. coriacea (Reeve, 1844), from West Africa, constitute two evolutionarily significant units (ESUs). We found that for the nominal subspecies, the variation in morphology (shell, radula and gross anatomy) and DNA sequences was not geographically structured, and this agrees with what we would expect in a species with high connectivity at the larval stage. The divergence between the two subspecies cannot be easily explained by isolation by distance, and we would argue that one or more extrinsic factors may have played a role in isolating the two ESUs and maintaining that isolation

Community clinic-based lifestyle change for prevention of metabolic syndrome: Rationale, design and methods of the ‘Vida Sana/healthy life’ program

Purpose and Objectives: The risk of diseases associated with Metabolic Syndrome (MetS) is higher for Hispanics living in the northeastern United States than for other racial and ethnic groups. Higher risk of diabetes, high blood lipids, obesity and limited access to continuity of care are all factors that also contribute to disproportionately poorer chronic disease outcomes for Hispanics. Intervention approach: This article describes the planning and implementation of, and evaluation plans for the Vida Sana Program (VSP), a community-based group intervention created to address the identified MetS risks by encouraging healthier diet and physical activity behaviors among a low-income, largely Spanish speaking, and literacy limited uninsured population. Developed in response to recent calls for culturally-tailored interventions, VSP is conducted by trained bicultural/bilingual Navegantes, who deliver a culturally sensitive, fun and engaging eight-week, in-person educational series through group meetings. The intervention also includes a 40-page colorful, picture and graphic enhanced booklet to be used in the group setting and at home. The intervention focused on screening for MetS-associated disease risk factors, understanding chronic disease management, encouraging medication adherence, increasing physical activity, and healthful dietary changes such as limiting alcohol, sodium, unhealthy fats and excess carbohydrate intake, while emphasizing portion control, whole grains and healthy fats. Conclusions: This creative, community-based approach fills an important gap in the community and in the public health literature, is well liked by health literacy limited patients, and will provide an important model of successfully engaging the Hispanic community on these important health issues

Estabilidade das propriedades hidráulicas do solo em um sistema de plantio direto em longo prazo

The area under the no-tillage system (NT) has been increasing over the last few years. Some authors indicate that stabilization of soil physical properties is reached after some years under NT while other authors debate this. The objective of this study was to determine the effect of the last crop in the rotation sequence (1st year: maize, 2nd year: soybean, 3rd year: wheat/soybean) on soil pore configuration and hydraulic properties in two different soils (site 1: loam, site 2: sandy loam) from the Argentinean Pampas region under long-term NT treatments in order to determine if stabilization of soil physical properties is reached apart from a specific time in the crop sequence. In addition, we compared two procedures for evaluating water-conducting macroporosities, and evaluated the efficiency of the pedotransfer function ROSETTA in estimating the parameters of the van Genuchten-Mualem (VGM) model in these soils. Soil pore configuration and hydraulic properties were not stable and changed according to the crop sequence and the last crop grown in both sites. For both sites, saturated hydraulic conductivity, K0, water-conducting macroporosity, εma, and flow-weighted mean pore radius, R0ma, increased from the 1st to the 2nd year of the crop sequence, and this was attributed to the creation of water-conducting macropores by the maize roots. The VGM model adequately described the water retention curve (WRC) for these soils, but not the hydraulic conductivity (K) vs tension (h) curve. The ROSETTA function failed in the estimation of these parameters. In summary, mean values of K0 ranged from 0.74 to 3.88 cm h-1. In studies on NT effects on soil physical properties, the crop effect must be considered.Nos últimos anos, o sistema plantio direto (NT) tem aumentado. Alguns autores indicam que os atributos físicos do solo ficam estáveis após anos cultivando nesse sistema, sendo esse fato discutido por outros autores. O objetivo deste trabalho foi avaliar o efeito do último cultivo após a rotação (1º ano: milho; 2º ano: soja; e 3º ano: trigo/soja) sobre a configuração do sistema poroso do solo e das suas propriedades hidráulicas de diferentes tipos de textura (solo 1: franco; e solo 2: franco-arenoso) da região do pampa argentino, em NT por um longo prazo, para determinar se a estabilidade das propriedades físicas do solo independe do momento da rotação. Adicionalmente, foram comparados os procedimentos para avaliar a macroporosidade, bem como avaliada a eficiência da função de pedotransferência ROSETTA, para estimar os parâmetros do modelo de van Genuchten-Mualen (VGM) desses solos. A configuração do sistema poroso do solo e as propriedades hidráulicas não foram estáveis e se alteraram em razão da rotação da cultura e do último cultivo utilizado na rotação em ambos os solos. Nos dois locais, a condutividade hidráulica do solo saturado (K0 ), a macroporosidade (εma) e o raio médio ponderado do poro por fluxo (R0ma) aumentaram do 1º para o 2º ano da rotação de culturas e isso se atribuiu ao aumento de macroporos condutores de água pra as raízes de milho. O modelo VGM descreveu adequadamente a curva de retenção de água (WCR) nos dois solos, porém não foi adequada para as curvas de condutividade hidráulica (K) vs tensão (h). A função ROSETTA não foi eficiente para a estimativa dos parâmetros. Em resumo, os valores médios de K0 variaram entre 0,74 e 3,88 cm h-1. Com relação às propriedades físicas do solo no NT, o efeito do cultivo deve ser considerado.Facultad de Ciencias Agrarias y Forestale

A gene expression atlas for different kinds of stress in the mouse brain

Stressful experiences are part of everyday life and animals have evolved physiological and behavioral responses aimed at coping with stress and maintaining homeostasis. However, repeated or intense stress can induce maladaptive reactions leading to behavioral disorders. Adaptations in the brain, mediated by changes in gene expression, have a crucial role in the stress response. Recent years have seen a tremendous increase in studies on the transcriptional effects of stress. The input raw data are freely available from public repositories and represent a wealth of information for further global and integrative retrospective analyses. We downloaded from the Sequence Read Archive 751 samples (SRA-experiments), from 18 independent BioProjects studying the effects of different stressors on the brain transcriptome in mice. We performed a massive bioinformatics re-analysis applying a single, standardized pipeline for computing differential gene expression. This data mining allowed the identification of novel candidate stress-related genes and specific signatures associated with different stress conditions. The large amount of computational results produced was systematized in the interactive “Stress Mice Portal”