Six new loci associated with body mass index highlight a neuronal influence on body weight regulation

Common variants at only two loci, FTO and MC4R, have been reproducibly associated with body mass index (BMI) in humans. To identify additional loci, we conducted meta-analysis of 15 genome-wide association studies for BMI (n > 32,000) and followed up top signals in 14 additional cohorts (n > 59,000). We strongly confirm FTO and MC4R and identify six additional loci (P < 5 x 10(-8)): TMEM18, KCTD15, GNPDA2, SH2B1, MTCH2 and NEGR1 (where a 45-kb deletion polymorphism is a candidate causal variant). Several of the likely causal genes are highly expressed or known to act in the central nervous system (CNS), emphasizing, as in rare monogenic forms of obesity, the role of the CNS in predisposition to obesity.

Increases in plasma sheet temperature with solar wind driving during substorm growth phases

During the substorm growth phase, magnetic reconnection extracts ~10^15 J from the solar wind through magnetic reconnection at the magnetopause, which is then stored in the magnetotail lobes. Plasma sheet pressure then increases to balance magnetic flux density increases in the lobes. We examine plasma sheet pressure, density and temperature during substorm growth phases using nine years of Cluster data (>316,000 data points). We show that plasma sheet pressure and temperature are higher during growth phases with higher solar wind driving whereas the density is approximately constant. We also show a weak correlation between plasma sheet temperature before onset and the minimum SuperMAG SML auroral index in the subsequent substorm. We discuss how energization of the plasma sheet before onset may result from thermodynamically adiabatic processes; how hotter plasma sheets may result in magnetotail instabilities and how this relates to the onset and size of the subsequent substorm expansion phase.

The solsticial pause on Mars: 1. A planetary wave reanalysis

Large-scale planetary waves are diagnosed from an analysis of profiles retrieved from the Thermal Emission Spectrometer aboard the Mars Global Surveyor spacecraft during its scientific mapping phase. The analysis is conducted by assimilating thermal profiles and total dust opacity retrievals into a Mars global circulation model. Transient waves are largest throughout the northern hemisphere autumn, winter and spring period and almost absent during the summer. The southern hemisphere exhibits generally weaker transient wave behaviour. A striking feature of the low-altitude transient waves in the analysis is that they show a broad subsidiary minimum in amplitude centred on the winter solstice, a period when the thermal contrast between the summer hemisphere and the winter pole is strongest and baroclinic wave activity might be expected to be strong. This behaviour, here called the ‘solsticial pause,’ is present in every year of the analysis. This strong pause is under-represented in many independent model experiments, which tend to produce relatively uniform baroclinic wave activity throughout the winter. This paper documents and diagnoses the transient wave solsticial pause found in the analysis; a companion paper investigates the origin of the phenomenon in a series of model experiments.

Ordinal judgements of depth in monocularly- and binocularly-viewed photographs of complex natural scenes

This study investigated the contribution of stereoscopic depth cues to the reliability of ordinal depth judgments in complex natural scenes. Participants viewed photographs of cluttered natural scenes, either monocularly or stereoscopically. On each trial, they judged which of two indicated points in the scene was closer in depth. We assessed the reliability of these judgments over repeated trials, and how well they correlated with the actual disparities of the points between the left and right eyes' views. The reliability of judgments increased as their depth separation increased, was higher when the points were on separate objects, and deteriorated for point pairs that were more widely separated in the image plane. Stereoscopic viewing improved sensitivity to depth for points on the same surface, but not for points on separate objects. Stereoscopic viewing thus provides depth information that is complementary to that available from monocular occlusion cues.

Phylogenetic relationships among species of Anopheles (Nyssorhynchus) (Diptera, Culicidae) based on nuclear and mitochondrial gene sequences

Phylogenetic relationships among 21 species of mosquitoes in subgenus Nyssorhynchus were inferred from the nuclear white and mitochondrial NADH dehydrogenase subunit 6 (ND6) genes. Bayestan phylogenetic methods found that none of the three Sections within Nyssorhynchus (Albimanus, Argyritarsis, Myzorhynchella) were supported in all analyses, although Myzorhynchella was found to be monophyletic at the combined genes Within the Albimanus Section the monophyly of the Stroder Subgroup was strongly supported and within the Myzorhynchella Section Anopheles anrunesi and An lutzu formed a strongly supported monophyletic group The epidemiologically significant Albitarsis Complex showed evidence of paraphyly (relative to An lanet-Myzorhynchella) and discordance across gene trees, and the previously synonomized species of An. dunhami and An goeldii were recovered as sister species Finally, there was evidence of complexes in several species, including An antunesi, An deaneorum, and An. strodei (c) 2010 Elsevier B.V. All rights reserved

MPO Inhibitors Selected by Virtual Screening

The hemeprotein myeloperoxidase (MPO) participates in innate immune defense through its ability to generate potent microbicidal oxidants. However, these oxidants are also key mediators of the tissue damage associated with many inflammatory diseases. Thus, there is considerable interest in developing therapeutically useful MPO inhibitors. Here, we used structure-based drug design (SBDD) and ligand-based drug design (LBDD) to select for potentially new and selective MPO inhibitors. A pharmacophore model was developed based on the crystal structure of human MPO in complex with salicylhydroxamic acid (SHA), a known inhibitor of the enzyme. The pharmacophore model was used to screen the ZINC database for potential ligands, which were further filtered on the basis of their physical-chemical properties and docking score. The filtered compounds were visually inspected, and nine were purchased for experimental studies. Surprisingly, almost all of the selected compounds belonged to the aromatic hydrazide class, which had been previously described as MPO inhibitors. The compounds selected by virtual screening were shown to inhibit the chlorinating activity of MPO; the top four compounds displayed IC(50) values ranging from 1.0 to 2.8 mM. MPO inactivation by the most effective compound was shown to be irreversible. Overall, our results show that SBDD and LBDD may be useful for the rational development of new MPO inhibitors.

Integration of Ligand- and Target-Based Virtual Screening for the Discovery of Cruzain Inhibitors

A myriad of methods are available for virtual screening of small organic compound databases. In this study we have successfully applied a quantitative model of consensus measurements, using a combination of 3D similarity searches (ROCS and EON), Hologram Quantitative Structure Activity Relationships (HQSAR) and docking (FRED, FlexX, Glide and AutoDock Vina), to retrieve cruzain inhibitors from collected databases. All methods were assessed individually and then combined in a Ligand-Based Virtual Screening (LBVS) and Target-Based Virtual Screening (TBVS) consensus scoring, using Receiving Operating Characteristic (ROC) curves to evaluate their performance. Three consensus strategies were used: scaled-rank-by-number, rank-by-rank and rank-by-vote, with the most thriving the scaled-rank-by-number strategy, considering that the stiff ROC curve appeared to be satisfactory in every way to indicate a higher enrichment power at early retrieval of active compounds from the database. The ligand-based method provided access to a robust and predictive HQSAR model that was developed to show superior discrimination between active and inactive compounds, which was also better than ROCS and EON procedures. Overall, the integration of fast computational techniques based on ligand and target structures resulted in a more efficient retrieval of cruzain inhibitors with desired pharmacological profiles that may be useful to advance the discovery of new trypanocidal agents.

Synthesis and Characterization of Ordered Intermetallic Nanostructured PtSn/C and PtSb/C and Evaluation as Electrodes for Alcohol Oxidation

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Proposal of convergence of e-Learning systems for t-Learning

This article presents considerations about viability on reutilize existing web based e-Learning systems on Interactive Digital TV environment according to Digital TV standard adopted in Brazil. Considering the popularity of Moodle system in academic and corporative area, such system was chosen as a foundation for a survey into its properties to create a specification of an Application Programming Interface (API) for convergence to t-Learning characteristics that demands efforts in interface design area due the fact that computer and TV concepts are totally different. This work aims to present studies concerning user interface design during two stages: survey and detail of functionalities from an e-Learning system and how to adapt them for the Interactive TV regarding usability context and Information Architecture concepts.

Electrochemical Properties of Oxo-Manganese Complex Biomimicking Enzyme Active Sites and Its Electrocatalytic Application for Dopamine Determination

This work describes the characterization of the [Mn2 IV,IVO2(terpy)2(H2O)2]4+ complex in aqueous solution by UV-vis spectrophotometry, cyclic voltammetry, and linear sweep voltammetry with a rotating disk electrode. The pH effect, potential scan rate, effect of perfluorosulfonate polymer, and anion of supporting electrode on the electrochemical behavior of the modified electrode for better performance were investigated. The potential peak of the modified electrode was linearly dependent upon the ratio [ionic charge]/[ionic radius]. The modified electrode exerted an electrocatalytic effect on dopamine oxidation in aqueous solution with a decrease in the overpotential compared with the unmodified glassy carbon electrode. This way, the modified electrode showed an enzymatic biomimicking behavior. Tafel plot analyses were used to elucidate the kinetics and mechanism of dopamine oxidation. © 2013 Springer Science+Business Media New York.

Improvement of the photocatalytic activity of magnetite by Mn-incorporation

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Dinâmica do relevo: quantificação de processos formadores

Pós-graduação em Geologia Regional - IGCE

Genome-wide methylation and transcriptome analysis in penile carcinoma: uncovering new molecular markers

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Avaliação do gasto energético de repouso em pacientes com sepse associada ou não à lesão renal aguda

Pós-graduação em Fisiopatologia em Clínica Médica - FMB