Alterations in receptor binding properties of recent human influenza H3N2 viruses are associated with reduced natural killer cell lysis of infected cells

Natural killer (NK) cell recognition of influenza virus-infected cells involves hemagglutinin (HA) binding to sialic acid (SA) on activating NK receptors. SA also acts as a receptor for the binding of influenza virus to its target host cells. The SA binding properties of H3N2 influenza viruses have been observed to change during circulation in humans: recent isolates are unable to agglutinate chicken red blood cells and show reduced affinity for synthetic glycopolymers representing SA-alpha-2,3-lactose (3'SL-PAA) and SA-alpha-2,6-N-acetyl lactosamine (6'SLN-PAA) carbohydrates. Here, NK lysis of cells infected with human H3N2 influenza viruses isolated between 1969 and 2003 was analyzed. Cells infected with recent isolates (1999 to 2003) were found to be lysed less effectively than cells infected with older isolates (1969 to 1996). This change occurred concurrently with the acquisition of two new potential glycosylation site motifs in RA. Deletion of the potential glycosylation site motif at 133 to 135 in HA1 from a recent isolate partially restored the agglutination phenotype to a recombinant virus, indicating that the HA-SA interaction is inhibited by the glycosylation modification. Deletion of either of the recently acquired potential glycosylation sites from HA led to increased NK lysis of cells infected with recombinant viruses carrying modified HA. These results indicate that alterations in RA glycosylation may affect NK cell recognition of influenza virus-infected cells in addition to virus binding to host cells.

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.

Hurricanes and climate: the U.S. CLIVAR working group on hurricanes

While a quantitative climate theory of tropical cyclone formation remains elusive, considerable progress has been made recently in our ability to simulate tropical cyclone climatologies and understand the relationship between climate and tropical cyclone formation. Climate models are now able to simulate a realistic rate of global tropical cyclone formation, although simulation of the Atlantic tropical cyclone climatology remains challenging unless horizontal resolutions finer than 50 km are employed. This article summarizes published research from the idealized experiments of the Hurricane Working Group of U.S. CLIVAR (CLImate VARiability and predictability of the ocean-atmosphere system). This work, combined with results from other model simulations, has strengthened relationships between tropical cyclone formation rates and climate variables such as mid-tropospheric vertical velocity, with decreased climatological vertical velocities leading to decreased tropical cyclone formation. Systematic differences are shown between experiments in which only sea surface temperature is increased versus experiments where only atmospheric carbon dioxide is increased, with the carbon dioxide experiments more likely to demonstrate the decrease in tropical cyclone numbers previously shown to be a common response of climate models in a warmer climate. Experiments where the two effects are combined also show decreases in numbers, but these tend to be less for models that demonstrate a strong tropical cyclone response to increased sea surface temperatures. Further experiments are proposed that may improve our understanding of the relationship between climate and tropical cyclone formation, including experiments with two-way interaction between the ocean and the atmosphere and variations in atmospheric aerosols.

Functional analysis of a novel missense NBC1 mutation and of other mutations causing proximal renal tubular acidosis

Mutations in the Na+-HCO3- cotransporter NBC1 cause severe proximal tubular acidosis (pRTA) associated with ocular abnormalities. Recent studies have suggested that at least some NBC1 mutants show abnormal trafficking in the polarized cells. This study identified a new homozygous NBC1 mutation (G486R) in a patient with severe pRTA. Functional analysis in Xenopus oocytes failed to detect the G486R activity due to poor surface expression. In ECV304 cells, however, G486R showed the efficient membrane expression, and its transport activity corresponded to approximately 50% of wild-type (WT) activity. In Madin-Darby canine kidney (MDCK) cells, G486R was predominantly expressed in the basolateral membrane domain as observed for WT. Among the previously identified NBC1 mutants that showed poor surface expression in oocytes, T485S showed the predominant basolateral expression in MDCK cells. On the other hand, L522P was exclusively retained in the cytoplasm in ECV304 and MDCK cells, and functional analysis in ECV304 cells failed to detect its transport activity. These results indicate that G486R, like T485S, is a partial loss of function mutation without major trafficking abnormalities, while L522P causes the clinical phenotypes mainly through its inability to reach the plasma membranes. Multiple experimental approaches would be required to elucidate potential disease mechanism by NBC1 mutations.

ADRB2 and LEPR Gene Polymorphisms: Synergistic Effects on the Risk of Obesity in Japanese

The objective of the present study was to validate a recently reported synergistic effect between variants located in the leptin receptor (LEPR) gene and in the beta-2 adrenergic receptor (ADRB2) gene on the risk of overweight/obesity. We studied a middle-aged/ elderly sample of 4,193 nondiabetic Japanese subjects stratified according gender (1,911 women and 2,282 men). The LEPR Gln223Arg (rs1137101) variant as well as both ADRB2 Arg16Gly (rs1042713) and Gln27Glu (rs1042714) polymorphisms were analyzed. The primary outcome was the risk of overweight/obesity defined as BMI >= 25 kg/m(2), whereas secondary outcomes included the risk of a BMI >= 27 kg/m(2) and BMI as a continuous variable. None of the studied polymorphisms showed statistically significant individual effects, regardless of the group or phenotype studied. Haplotype analysis also did not disclose any associations of ADRB2 polymorphisms with BMI. However, dimensionality reduction-based models confirmed significant interactions among the investigated variants for BMI as a continuous variable as well as for the risk of obesity defined as BMI >= 27 kg/m(2). All disclosed interactions were found in men only. Our results provide external validation for a male specific ADRB2-LEPR interaction effect on the risk of overweight/obesity, but indicate that effect sizes associated with these interactions may be smaller in the population studied.

Isolation and characterization of 15 microsatellite loci in the stingless bee Plebeia remota (Apidae: Meliponini)

The destruction of Brazilian natural habitats has reduced bee populations and negative impacts of native flora pollination have been noticed. This work describes the isolation and characterization of microsatellite loci and evaluates them as molecular markers to study genetic variability of the stingless bee Plebeia remota. A microsatellite enriched genomic library was constructed and 15 primer pairs were designed for this species. The survey was conducted by analyzing 21 unrelated individuals. Genetic diversity indexes were calculated. The mean allelic richness was 6.3, the observed heterozygosity was 0.568, and the percentage of polymorphic loci was 93.33%. Also the primers were tested in cross-species amplification and showed promising results for P. droryana, P. emerina, P. lucii, P. meridionalis, P. pugnax, and P. saiqui. The microsatellite loci described here will be useful to evaluate genetic variability of stingless bees, and certainly will improve our knowledge about population dynamics especially in threatened environments.

Characterization of microsatellite loci of Tetragonisca angustula (Hymenoptera, Apidae, Meliponini)

An enriched genomic library was constructed from Tetragonisca angustula, a stingless bee species widely distributed in Brazil. The library was screened using two simple-repeat oligonucleotide probes and 21 microsatellite primer pairs were designed flanking a selection of repeat sequences within positive clones. The polymorphism of the microsatellite loci was analyzed by screening a sample of 19 unrelated T. angustula workers. Fifteen out of 21 loci were shown to be polymorphic, with observed heterozygosity estimates ranging from 0.00 to 0.89. The primers were also successfully used to amplify microsatellite loci from other stingless bee species, Tetragonisca fiebrigi, Tetragonisca weyrauchi, Lestrimelitta maracaia and Schwarziana quadripunctata. The results from variability analyses suggest that the microsatellite loci isolated from T. angustula will be useful in further population studies for the species and also for other Meliponini.

Localization of Cathepsins D and B at the Maternal-Fetal Interface and the Invasiveness of the Trophoblast during the Postimplantation Period in the Mouse

A survey of existing data suggests that trophoblast cells produce factors involved in extracellular matrix degradation. In this study, we correlated the expression of cathepsins D and B in the murine ectoplacental cone with the ultrastructural progress of decidual invasion by trophoblast cells. Both proteases were immunolocalized at implantation sites in lysosome-endosome-like compartments of trophoblast giant cells. Cathepsin D, but not cathepsin B, was also detected ultrastructurally in extracellular compartments surrounded by processes of the invading trophoblast containing extracellular matrix components and endometrial cell debris. The expression of cathepsins D and B by trophoblast cells was confirmed by RT-PCR in ectoplacental cones isolated from implantation chambers at gestation day 7.5. Our data addressed a positive relationship between the expression and presence of cathepsin D at the extracellular compartment of the maternal-fetal interface and the invasiveness of the trophoblast during the postimplantation period, suggesting a participation of invading trophoblast cells in the cathepsin D release. Such findings indicate that mouse trophoblast cells might exhibit a proteolytic ability to partake in the decidual invasion process at the maternal-fetal interface. Copyright (C) 2010 S. Karger AG, Basel

Effects of cyclooxygenase inhibitors on parasite burden, anemia and oxidative stress in murine Trypanosoma cruzi infection

Prostaglandins are known to be produced by macrophages when challenged with Trypanosoma cruzi, the etiological agent of Chagas` disease. It is not known whether these lipid mediators play a role in oxidative stress in host defenses against this important protozoan parasite. In this study, we demonstrated that inducible cyclooxygenase-mediated prostaglandin production is a key chemical mediator in the control of parasite burden and erythrocyte oxidative stress during T. cruzi infection in C57BL/6 and BALB/c mice, prototype hosts for the study of resistance and susceptibility in murine Chagas` disease. The results suggested the existence of at least two mechanisms of oxidative stress, dependent or independent with regard to the nitric oxide and cyclooxygenase pathway, where one or the other is more evident depending on the mouse strain.

5-Lipoxygenase plays a role in the control of parasite burden and contributes to oxidative damage of erythrocytes in murine Chagas` disease

Chagas` disease is accompanied by severe anemia and oxidative stress, which may contribute to mortality. In this study, we investigated the role of 5-lipoxygenase (5-LO) in the control of parasitism and anemia associated with oxidative damage of erythrocytes in experimental Trypanosoma cruzi infection. Wild-type C57BL/6, 129Sv mice treated or not with nordihydroguaiaretic acid (NDGA, 5-LO inhibitor), mice lacking the 5-LO enzyme gene (5-LO(-/-)) and inducible nitric oxide synthase gene (iNOS(-/-)) were infected with the Y strain of T cruzi. impairment of 5-LO resulted in increased numbers of trypomastigote forms in the blood and amastigote forms in the heart of infected mice. We assessed oxidative stress in erythrocytes by measuring oxygen uptake, induction time and chemiluminescence following treatment with tert-butyl hydroperoxide (TBH). Our results show that 5-LO metabolites increased lipid peroxidation levels in erythrocytes during the early phase of murine T cruzi infection. NDGA treatment reduced oxidative damage of erythrocytes in C57BL/6 T cruzi-infected mice but not in C57BL/6 iNOS-/- infected mice, showing that the action of NDGA is dependent on endogenous nitric oxide (NO). In addition, our results show that 5-LO metabolites do not participate directly in the development of anemia in infected mice. We conclude that 5-LO products may not only play a major role in controlling heart tissue parasitism, i.e., host resistance to acute infection with T cruzi in vivo, but in the event of an infection also play an important part in erythrocyte oxidative stress, an NO-dependent effect. (C) 2009 Elsevier B.V. All rights reserved.

Economias de escala e eficiência de gastos na saúde : novas evidências

Uma das mais importantes diretrizes do Sistema Único de Saúde (SUS) é a descentralização da gestão dos serviços de saúde, visando uma maior proximidade dos agentes tomadores de decisão com a população local. Contudo, um dos argumentos contrários à descentralização é de que esta pode implicar em consideráveis perdas de escala. Este trabalho tem como objetivo investigar a existência de economias de escala no setor de saúde pública no Brasil. Alguns estudos empíricos nacionais já encontraram evidências de economias de escala na provisão de serviços públicos em geral, incluindo o caso específico do setor de saúde, como os trabalhos de Souza, Cribari-Neto e Stosic (2005) e Mattos et al. (2009). Este estudo busca acrescentar novas evidências a esse tema, a partir de uma nova investigação que difere das anteriores em metodologia. Inicialmente é calculado um score de eficiência (através do método DEA - Data envelopment analysis) com base em três variáveis de insumo (gastos em saúde, cobertura de esgoto e de abastecimento de água encanada) e três variáveis de produto (mortalidade infantil, internação por doenças infecciosas e taxa de acesso ao sistema de saúde). Após o cálculo deste score, analisa-se a relação entre tamanho da população e outras variáveis demográficas e a eficiência dos municípios na provisão de saúde. Para isso foi feita uma regressão usando dados de painel que inclui 537 dos 645 municípios do Estado de São Paulo ao longo do período 2002-2007, o que permite o controle do efeito fixo dos municípios, além do controle de características como renda per capita, violência, educação, entre outros. Os resultados confirmam aqueles já encontrados por outros pesquisadores a partir de outras metodologias, revelando que o tamanho do município é um importante determinante de sua eficiência na área de saúde. Assim sendo, por fim, investigam-se possíveis explicações para o forte impacto da escala na eficiência de gastos em saúde. A questão que surge é a identificação dos fatores que determinam essas economias de escala, que podem vir, por exemplo, dos gastos em infra-estrutura – como quantidade de leitos e estabelecimentos – ou de gastos com recursos humanos, equipamentos, materiais ou remédios. Parte desta questão é analisada ao se estimar um modelo de regressões aparentemente não correlacionadas, no qual se identificam diferenças relevantes na intensidade de utilização de diferentes categorias de insumos de acordo com o tamanho da população.

Flexible information acquisition and optimal Tobin tax in tractable dynamic global games

My dissertation focuses on dynamic aspects of coordination processes such as reversibility of early actions, option to delay decisions, and learning of the environment from the observation of other people’s actions. This study proposes the use of tractable dynamic global games where players privately and passively learn about their actions’ true payoffs and are able to adjust early investment decisions to the arrival of new information to investigate the consequences of the presence of liquidity shocks to the performance of a Tobin tax as a policy intended to foster coordination success (chapter 1), and the adequacy of the use of a Tobin tax in order to reduce an economy’s vulnerability to sudden stops (chapter 2). Then, it analyzes players’ incentive to acquire costly information in a sequential decision setting (chapter 3). In chapter 1, a continuum of foreign agents decide whether to enter or not in an investment project. A fraction λ of them are hit by liquidity restrictions in a second period and are forced to withdraw early investment or precluded from investing in the interim period, depending on the actions they chose in the first period. Players not affected by the liquidity shock are able to revise early decisions. Coordination success is increasing in the aggregate investment and decreasing in the aggregate volume of capital exit. Without liquidity shocks, aggregate investment is (in a pivotal contingency) invariant to frictions like a tax on short term capitals. In this case, a Tobin tax always increases success incidence. In the presence of liquidity shocks, this invariance result no longer holds in equilibrium. A Tobin tax becomes harmful to aggregate investment, which may reduces success incidence if the economy does not benefit enough from avoiding capital reversals. It is shown that the Tobin tax that maximizes the ex-ante probability of successfully coordinated investment is decreasing in the liquidity shock. Chapter 2 studies the effects of a Tobin tax in the same setting of the global game model proposed in chapter 1, with the exception that the liquidity shock is considered stochastic, i.e, there is also aggregate uncertainty about the extension of the liquidity restrictions. It identifies conditions under which, in the unique equilibrium of the model with low probability of liquidity shocks but large dry-ups, a Tobin tax is welfare improving, helping agents to coordinate on the good outcome. The model provides a rationale for a Tobin tax on economies that are prone to sudden stops. The optimal Tobin tax tends to be larger when capital reversals are more harmful and when the fraction of agents hit by liquidity shocks is smaller. Chapter 3 focuses on information acquisition in a sequential decision game with payoff complementar- ity and information externality. When information is cheap relatively to players’ incentive to coordinate actions, only the first player chooses to process information; the second player learns about the true payoff distribution from the observation of the first player’s decision and follows her action. Miscoordination requires that both players privately precess information, which tends to happen when it is expensive and the prior knowledge about the distribution of the payoffs has a large variance.

Do encantamento dos números à realidade dos fatos: conciliação entre os balanços patrimonial e social da ALUNORTE

The social balance is turning into an instrument capable of identifying the Organizational Commitment socio-environmental. The objective of the Social Balance is to present the application of company resources on socio-environmental investments internally and externally. The research was developed based on the Balance Social and Sheet from Alumina North Brazil S / A, ALUNORTE, for fiscal years 2008 and 2009, with the purpose of describing the finding of the Balance Social and Sheet from ALUNORTE about social responsibility. To validate the proposal were doing comparisons between accounting and financial datas from Alunorte and Y.Yamada, in order to highlight what they say and indicators confirm the privileges of the first against second

Modo de aplicação e eficiência de inseticidas granulados sistêmicos para o controle de cigarras (Hemiptera: Cicadidae) do cafeeiro

Avaliou-se a eficiência de métodos de aplicação de inseticidas granulados sistêmicos para o controle das cigarras Quesada gigas (Olivier) e Dorisiana drewseni (Stål) do cafeeiro (Coffea arabica). O ensaio foi conduzido em cafezal cv. Mundo Novo com idade de seis anos, espaçamento de 3,5 X 1,5 m, com uma planta/cova, no ano agrícola 1992/1993. Utilizou-se um delineamento em blocos casualizados, com 21 tratamentos e 4 repetições, cada uma contendo parcelas de cinco plantas. Os tratamentos consistiram nas aplicações dos produtos triadimenol + disulfoton 1,5% + 7,5% (26 g/cova), aldicarb 150G (10,00 g/cova), ethoprophos 100G (30,00 g/cova), phorate 5G (80,00 g/cova) e terbufos 5G (40,00 g/cova) em quatro modalidades de aplicação: aplicador costal manual Mebuki TF8; canequinha, lançando o produto para o ápice da planta; aplicador tratorizado Kamaq CK2-AG; e sulcos em meia lua, abertos manualmente, na projeção da copa. As avaliações foram realizadas aos 70, 105 e 140 dias após aplicação dos produtos, onde foram efetuadas aberturas de trincheiras de 50 X 50 X 50cm por cova, procedendo-se a contagem do número de ninfas vivas. Concluiu-se que o aplicador costal manual e canequinha revelaram-se os mais eficientes (86,0 - 93,5% e 76,8 - 86,7%, respectivamente); aplicação tratorizada e sulcos na projeção de copa tiveram sua eficiência variável com o produto utilizado; terbufos apresentou maior redução da população (98,2 - 100%) e phorate (79,6 - 99,1%) e a mistura triadimenol + disulfoton (82,3 - 97,3%) apresentaram alta eficiência, não diferindo do terbufos. Aldicarb apresentou desempenho satisfatório (68,1 - 85,0%) conforme o modo de aplicação e ethoprophos não foi eficaz quando aplicado com o aplicador costal manual (58,4%), canequinha (45,1%) e sulco (31,9%).