Postnatal catch-up growth leads to higher p66Shc and mitochondrial dysfunction.

Epidemiological data suggest an inverse relationship between birth weight and long-term metabolic deficits, which is exacerbated by postnatal catch-up growth. We have previously demonstrated that rat offspring subject to maternal protein restriction (MPR) followed by catch-up growth exhibit impaired hepatic function and ER stress. Given that mitochondrial dysfunction is associated with various metabolic pathologies, we hypothesized that altered expression of p66Shc, a gatekeeper of oxidative stress and mitochondrial function, contributes to the hepatic defects observed in MPR offspring. To test this hypothesis, pregnant Wistar rats were fed a control (20% protein) diet or an isocaloric low protein (8%; LP) diet throughout gestation. Offspring born to control dams received a control diet in postnatal life, while MPR offspring remained on a LP diet (LP1) or received a control diet post-weaning (LP2) or at birth (LP3). At four months, LP2 offspring exhibited increased protein abundance of both p66Shc and the cis-trans isomerase Pin1. This was further associated with aberrant markers of oxidative stress (i.e., elevated 4-HNE, SOD-1 and SOD2, decreased catalase) and aerobic metabolism (i.e., increased phospho-PDH and LDHa, decreased complex II, citrate synthase and TFAM). We further demonstrated that tunicamycin-induced ER stress in HepG2 cells led to increased p66Shc protein abundance, suggesting that ER stress may underlie the programmed effects observed in vivo. In summary, because these defects are exclusive to adult LP2 offspring, it is possible that a low protein diet during perinatal life, a period of liver plasticity, followed by catch-up growth is detrimental to long-term mitochondrial function

Characterization of a second open reading frame in genome segment 10 of bluetongue virus

Viruses have often evolved overlapping reading frames in order to maximise their coding capacity. Until recently, the segmented double-stranded (ds) RNA genome of viruses of the Orbivirus genus was thought to be monocistronic but the identification of the bluetongue virus (BTV) NS4 protein changed this assumption. A small open reading frame (ORF) in segment 10, overlapping the NS3 ORF in the +1 position that is maintained in more than 300 strains of the 26 different BTV serotypes and in more of 200 strains of the phylogenetically related African horse sickness (AHSV). In BTV, this ORF (named S10-ORF2 in this study) encodes a putative protein of 50-59 amino acid residues in length and appears to be under a strong positive selection. HA- or GFP-tagged versions of S10-ORF2 expressed from transfected plasmids localised within the nucleoli of transfected cells unless a putative nucleolar localisation signal was mutated S10-ORF2 inhibited gene expression, but not RNA translation, in transient transfection reporter assays. In both mammalian and insect cells, BTV S10-ORF2 deletion mutants (BTV8ΔS10-ORF2) displayed similar replication kinetics to wild type virus. In vivo, S10-ORF2 deletion mutants were pathogenic in mouse models of disease. Although further evidence is required for S10-ORF2 expression during infection, the data presented provide an initial characterisation of this open reading frame

Olive oil diet in mild pre-gestational diabetes impacts offspring β-cell development.

Maternal diabetes impairs fetal development and increases the risk of metabolic diseases in the offspring. Previously, we showed maternal dietary supplementation with 6% of olive oil prevents diabetes-induced embryo and fetal defects, in part, through the activation of peroxisome proliferator-activated receptors (PPARs). In this study we examined the effects of this diet on neonatal and adult pancreatic development in both male and female offspring. A mild diabetic model was developed by injecting neonatal rats with streptozotocin (90 mg/kg). During pregnancy these dams were fed a chow diet supplemented or not with 6% olive oil. Dual immunohistochemistry was performed to detect α and β cells in islets at post-natal day 2 and at 5 months of age. Morphometric analysis was carried out to determine the number of islets, α and β cell clusters and β-cell mass. At 5 months, male offspring of diabetic mothers had reduced β-cell mass. Moreover, this β-cell pancreatic deficit was prevented by the maternal supplementation with olive oil. While no changes in PPARα expression was detected in the pancreas, both PPARβ/δ and PPARγ expression were reduced in 5-month-old male offspring of diabetic rats. Interestingly, the reduction in PPAR β/δ expression was prevented by maternal olive-oil supplementation. To further explore the direct effects on PPARs, INS-1E (β) and αTC1-6 (α) cell lines were treated with oleic acid. Interestingly PPARβ/δ expression is highly expressed in INS-1E. Collectively, these findings suggest that olive oil supplementation in utero may prevent diabetes-induced β cell loss in postnatal life by modulating pancreatic PPARs

Addition of olive oil to diet of rats with mild pre-gestational diabetes impacts offspring β-cell development

Maternal diabetes impairs fetal development and increases the risk of metabolic diseases in the offspring. Previously, we demonstrated that maternal dietary supplementation with 6% of olive oil prevents diabetes-induced embryo and fetal defects, in part, through the activation of peroxisome proliferator-activated receptors (PPARs). In this study, we examined the effects of this diet on neonatal and adult pancreatic development in male and female offspring of mothers affected with pre-gestational diabetes. A mild diabetic model was developed by injecting neonatal rats with streptozotocin (90 mg/kg). During pregnancy, these dams were fed a chow diet supplemented or not with 6% olive oil. Offspring pancreata was examined at day 2 and 5 months of age by immunohistochemistry followed by morphometric analysis to determine number of islets, α and β cell clusters and β-cell mass. At 5 months, male offspring of diabetic mothers had reduced β-cell mass that was prevented by maternal supplementation with olive oil. PPARα and PPARγ were localized mainly in α cells and PPARβ/δ in both α and β cells. Although Pparβ/δ and Pparγ RNA expression showed reduction in 5-month-old male offspring of diabetic rats, Pparβ/δ expression returned to control levels after olive-oil supplementation. Interestingly, in vitro exposure to oleic acid (major component of olive oil) and natural PPAR agonists such as LTB4, CPC and 15dPGJ2 also significantly increased expression of all Ppars in αTC1–6 cells. However, only oleic acid and 15dPGJ2 increased insulin and Pdx-1 expression in INS-1E cells suggesting a protective role in β-cells. Olive oil may be considered a dietary supplement to improve islet function in offspring of affected mothers with pre-gestational diabetes.Fil: Taqui, Bushra. Western University; CanadáFil: Asadi, Farzad. Western University; CanadáFil: Capobianco, Evangelina Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Hardy, Daniel Barry. Western University; CanadáFil: Jawerbaum, Alicia Sandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Arany, Edith Juliana. Western University; Canad

Piloted Simulation Tests of Propulsion Control as Backup to Loss of Primary Flight Controls for a B747-400 Jet Transport

Partial failures of aircraft primary flight control systems and structural damages to aircraft during flight have led to catastrophic accidents with subsequent loss of lives (e.g. DC-10, B-747, C-5, B-52, and others). Following the DC-10 accident at Sioux City, Iowa in 1989, the National Transportation Safety Board recommended 'Encourage research and development of backup flight control systems for newly certified wide-body airplanes that utilize an alternate source of motive power separate from that source used for the conventional control system.' This report describes the concept of a propulsion controlled aircraft (PCA), discusses pilot controls, displays, and procedures; and presents the results of a PCA piloted simulation test and evaluation of the B747-400 airplane conducted at NASA Ames Research Center in December, 1996. The purpose of the test was to develop and evaluate propulsion control throughout the full flight envelope of the B747-400 including worst case scenarios of engine failures and out of trim moments. Pilot ratings of PCA performance ranged from adequate to satisfactory. PCA performed well in unusual attitude recoveries at 35,000 ft altitude, performed well in fully coupled ILS approaches, performed well in single engine failures, and performed well at aft cg. PCA performance was primarily limited by out-of-trim moments

OpenTox predictive toxicology framework: toxicological ontology and semantic media wiki-based OpenToxipedia

<p>Abstract</p> <p>Background</p> <p>The OpenTox Framework, developed by the partners in the OpenTox project (<url>http://www.opentox.org</url>), aims at providing a unified access to toxicity data, predictive models and validation procedures. Interoperability of resources is achieved using a common information model, based on the OpenTox ontologies, describing predictive algorithms, models and toxicity data. As toxicological data may come from different, heterogeneous sources, a deployed ontology, unifying the terminology and the resources, is critical for the rational and reliable organization of the data, and its automatic processing.</p> <p>Results</p> <p>The following related ontologies have been developed for OpenTox: a) Toxicological ontology – listing the toxicological endpoints; b) Organs system and Effects ontology – addressing organs, targets/examinations and effects observed in <it>in vivo</it> studies; c) ToxML ontology – representing semi-automatic conversion of the ToxML schema; d) OpenTox ontology– representation of OpenTox framework components: chemical compounds, datasets, types of algorithms, models and validation web services; e) ToxLink–ToxCast assays ontology and f) OpenToxipedia community knowledge resource on toxicology terminology.</p> <p>OpenTox components are made available through standardized REST web services, where every compound, data set, and predictive method has a unique resolvable address (URI), used to retrieve its Resource Description Framework (RDF) representation, or to initiate the associated calculations and generate new RDF-based resources.</p> <p>The services support the integration of toxicity and chemical data from various sources, the generation and validation of computer models for toxic effects, seamless integration of new algorithms and scientifically sound validation routines and provide a flexible framework, which allows building arbitrary number of applications, tailored to solving different problems by end users (e.g. toxicologists).</p> <p>Availability</p> <p>The OpenTox toxicological ontology projects may be accessed via the OpenTox ontology development page <url>http://www.opentox.org/dev/ontology</url>; the OpenTox ontology is available as OWL at <url>http://opentox.org/api/1 1/opentox.owl</url>, the ToxML - OWL conversion utility is an open source resource available at <url>http://ambit.svn.sourceforge.net/viewvc/ambit/branches/toxml-utils/</url></p

The high-velocity clouds and the Magellanic Clouds

From an analysis of the sky and velocity distributions of the high-velocity clouds (HVCs) we show that the majority of the HVCs has a common origin. We conclude that the HVCs surround the Galaxy, forming a metacloud of 300 kpc in size and with a mass of 3 10^9 M_sun, and that they are the product of a powerful ``superwind'' (about 10^58 ergs), which occurred in the Magellanic Clouds about 570 Myr ago as a consequence of the interaction of the Large and Small Magellanic Clouds. The HVCs might be magnetic bubbles of semi-ionized gas, blown from the Magellanic Clouds around 570 Myr ago, that circulate largely through the halo of the Galaxy as a stream or flow of gas.Comment: 28 pages with 23 figure

The eNanoMapper database for nanomaterial safety information

Background: The NanoSafety Cluster, a cluster of projects funded by the European Commision, identified the need for a computational infrastructure for toxicological data management of engineered nanomaterials (ENMs). Ontologies, open standards, and interoperable designs were envisioned to empower a harmonized approach to European research in nanotechnology. This setting provides a number of opportunities and challenges in the representation of nanomaterials data and the integration of ENM information originating from diverse systems. Within this cluster, eNanoMapper works towards supporting the collaborative safety assessment for ENMs by creating a modular and extensible infrastructure for data sharing, data analysis, and building computational toxicology models for ENMs. Results: The eNanoMapper database solution builds on the previous experience of the consortium partners in supporting diverse data through flexible data storage, open source components and web services. We have recently described the design of the eNanoMapper prototype database along with a summary of challenges in the representation of ENM data and an extensive review of existing nano-related data models, databases, and nanomaterials-related entries in chemical and toxicogenomic databases. This paper continues with a focus on the database functionality exposed through its application programming interface (API), and its use in visualisation and modelling. Considering the preferred community practice of using spreadsheet templates, we developed a configurable spreadsheet parser facilitating user friendly data preparation and data upload. We further present a web application able to retrieve the experimental data via the API and analyze it with multiple data preprocessing and machine learning algorithms. Conclusion: We demonstrate how the eNanoMapper database is used to import and publish online ENM and assay data from several data sources, how the “representational state transfer” (REST) API enables building user friendly interfaces and graphical summaries of the data, and how these resources facilitate the modelling of reproducible quantitative structure–activity relationships for nanomaterials (NanoQSAR)

I am great, but only when I also want to dominate: Maladaptive narcissism moderates the relationship between adaptive narcissism and performance under pressure

Narcissism-performance research has focused on grandiose narcissism but has not examined the interaction between its so-called adaptive (reflecting over-confidence) and maladaptive (reflecting a domineering orientation) components. In this research, we tested interactions between adaptive and maladaptive narcissism using two motor tasks (basketball and golf in Experiments 1-2, respectively) and a cognitive task (letter transformation; Experiment 3). Across all experiments, adaptive narcissism predicted performance under pressure only when maladaptive narcissism was high. In the presence of maladaptive narcissism, adaptive narcissism also predicted decreased pre-putt time in Experiment 2 and an adaptive psychophysiological response in Experiment 3, reflecting better processing efficiency. Findings suggest that individuals high in both aspects of narcissism perform better under pressure thanks to superior task processing. In performance contexts, the terms “adaptive” and “maladaptive” – adopted from social psychology – are over-simplistic and inaccurate. We believe that self-inflated narcissism and dominant narcissism are better monikers for these constructs.N/