Replication enhancer elements within the open reading frame of tick-borne encephalitis virus and their evolution within the Flavivirus genus

We provide experimental evidence of a replication enhancer element (REE) within the capsid gene of tick-borne encephalitis virus (TBEV, genus Flavivirus). Thermodynamic and phylogenetic analyses predicted that the REE folds as a long stable stem–loop (designated SL6), conserved among all tick-borne flaviviruses (TBFV). Homologous sequences and potential base pairing were found in the corresponding regions of mosquito-borne flaviviruses, but not in more genetically distant flaviviruses. To investigate the role of SL6, nucleotide substitutions were introduced which changed a conserved hexanucleotide motif, the conformation of the terminal loop and the base-paired dsRNA stacking. Substitutions were made within a TBEV reverse genetic system and recovered mutants were compared for plaque morphology, single-step replication kinetics and cytopathic effect. The greatest phenotypic changes were observed in mutants with a destabilized stem. Point mutations in the conserved hexanucleotide motif of the terminal loop caused moderate virus attenuation. However, all mutants eventually reached the titre of wild-type virus late post-infection. Thus, although not essential for growth in tissue culture, the SL6 REE acts to up-regulate virus replication. We hypothesize that this modulatory role may be important for TBEV survival in nature, where the virus circulates by non-viraemic transmission between infected and non-infected ticks, during co-feeding on local rodents.

The SV2A ligand levetiracetam inhibits presynaptic Ca2+ channels via an intracellular pathway

Levetiracetam (LEV) is a prominent antiepileptic drug (AED) which binds to neuronal synaptic vesicle glycoprotein 2A (SV2A) protein and has reported effects on ion channels, but retains a poorly-defined mechanism of action. Here, we investigate inhibition of voltage-dependent Ca2+ (CaV) channels as a potential mechanism by which LEV imparts effects on neuronal activity. We used electrophysiological methods to investigate the effects of LEV on cholinergic synaptic transmission and CaV channel activity in superior cervical ganglion neurons (SCGNs). In parallel, we investigated effects of the LEV ‘inactive’ R-enantiomer, UCB L060. Thus, LEV, but not UCB L060 (each 100 μM), inhibited synaptic transmission between SCGNs in long-term culture in a time-dependent manner, significantly reducing excitatory postsynaptic potentials (EPSP) following ≥30 min application. In isolated SCGNs, LEV pretreatment (≥1 h), but not acute (5 min) application, significantly inhibited whole-cell IBa amplitude. In current clamp recordings, LEV reduced the amplitude of the afterhyperpolarizing potential (AHP) in a Ca2+-dependent manner, but also increased action potential (AP) latency in a Ca2+-independent manner, suggesting further mechanisms associated with reduced excitability. Intracellular LEV application (4-5 min) caused a rapid inhibition of IBa amplitude to an extent comparable to that seen following extracellular LEV pretreatment ( ≥ 1 h). Neither pretreatment nor intracellular application of UCB L060 produced any inhibitory effects on IBa amplitude. These results identify a stereospecific intracellular pathway by which LEV inhibits presynaptic CaV channels; resultant reductions in neuronal excitability are proposed to contribute to the anticonvulsant effects of LEV.

Intergenerational wealth mobility in rural Bangladesh

Unique residential history data with retrospective information on parental assets are used to study household wealth mobility in 141 villages in rural Bangladesh. Regression estimates of father–son correlations and analyses of intergenerational transition matrices show substantial persistence in wealth even when we correct for measurement errors in parental wealth. We do not find wealth mobility to be higher between periods of a person's life than between generations. We find that the process of household division plays an important role: sons who splinter off from the father's household experience greater (albeit downward) mobility in wealth. Despite significant occupational mobility across generations, its contribution to wealth mobility, net of human capital attainment of individuals, appears insignificant. Low wealth mobility in our data is primarily explained by intergenerational persistence in educational attainment.

Within-host evolution of Staphylococcus aureus during asymptomatic carriage

Background Staphylococcus aureus is a major cause of healthcare associated mortality, but like many important bacterial pathogens, it is a common constituent of the normal human body flora. Around a third of healthy adults are carriers. Recent evidence suggests that evolution of S. aureus during nasal carriage may be associated with progression to invasive disease. However, a more detailed understanding of within-host evolution under natural conditions is required to appreciate the evolutionary and mechanistic reasons why commensal bacteria such as S. aureus cause disease. Therefore we examined in detail the evolutionary dynamics of normal, asymptomatic carriage. Sequencing a total of 131 genomes across 13 singly colonized hosts using the Illumina platform, we investigated diversity, selection, population dynamics and transmission during the short-term evolution of S. aureus. Principal Findings We characterized the processes by which the raw material for evolution is generated: micro-mutation (point mutation and small insertions/deletions), macro-mutation (large insertions/deletions) and the loss or acquisition of mobile elements (plasmids and bacteriophages). Through an analysis of synonymous, non-synonymous and intergenic mutations we discovered a fitness landscape dominated by purifying selection, with rare examples of adaptive change in genes encoding surface-anchored proteins and an enterotoxin. We found evidence for dramatic, hundred-fold fluctuations in the size of the within-host population over time, which we related to the cycle of colonization and clearance. Using a newly-developed population genetics approach to detect recent transmission among hosts, we revealed evidence for recent transmission between some of our subjects, including a husband and wife both carrying populations of methicillin-resistant S. aureus (MRSA). Significance This investigation begins to paint a picture of the within-host evolution of an important bacterial pathogen during its prevailing natural state, asymptomatic carriage. These results also have wider significance as a benchmark for future systematic studies of evolution during invasive S. aureus disease.

Experimental evolution for generalists and specialists reveals multivariate genetic constraints on thermal reaction norms

Theory predicts the emergence of generalists in variable environments and antagonistic pleiotropy to favour specialists in constant environments, but empirical data seldom support such generalist–specialist trade-offs. We selected for generalists and specialists in the dung fly Sepsis punctum (Diptera: Sepsidae) under conditions that we predicted would reveal antagonistic pleiotropy and multivariate trade-offs underlying thermal reaction norms for juvenile development. We performed replicated laboratory evolution using four treatments: adaptation at a hot (31 °C) or a cold (15 °C) temperature, or under regimes fluctuating between these temperatures, either within or between generations. After 20 generations, we assessed parental effects and genetic responses of thermal reaction norms for three correlated life-history traits: size at maturity, juvenile growth rate and juvenile survival. We find evidence for antagonistic pleiotropy for performance at hot and cold temperatures, and a temperature-mediated trade-off between juvenile survival and size at maturity, suggesting that trade-offs associated with environmental tolerance can arise via intensified evolutionary compromises between genetically correlated traits. However, despite this antagonistic pleiotropy, we found no support for the evolution of increased thermal tolerance breadth at the expense of reduced maximal performance, suggesting low genetic variance in the generalist–specialist dimension.

Patriarchal values : girls are more apt to change

Patriarchal values: girls are more apt to change How has the family value system changed between generations, especially when taking into account the gender dimension? This article presents some results from a study carried outin 2007 in one village of the Gourani tribe where the people are followers of Ahle Hagh in Islamabad Gharb (west of Iran). The differences between generations (those born and raised before and after the Islamic Revolution) in patriarchal values in the family are statistically significant. The older generation opts for the man of the family to make most of the decisions; on children’s education, marriage, naming, the families expenditure, the place for residence, the social network of the family and even the number of children. The younger generation has a different value system and it has moved towards a more egalitarian type of family. With the gender variable included in the findings we see that although the values of the younger male population have evolved toward a less patriarchal decision making structure inthe family, the degree of changes among the young women is much higher. Looking into the preferences for male sex for the first child as well as a larger number of boys in the family, the difference between generations is significant. However data on the differences analyzed with the gender variable proves that the changes concerning the equality of sexes are mainly due to drastic changes in the young women’s value system. That is, the male population, young or old, still prefer to have a boy as their first born and to have more sons in the family. But the young female generation in the rural area sees less difference in having boys or girls in the family. It is concluded that reforms in the old value system is an evolving process of everyday life and that the girls are the main social force for change.

Men barnen då? : Ekonomiskt bistånd och det sociala arvet mellan föräldrar och barn

I denna kvalitativa studie har vi valt att undersöka hur man på enheten för ekonomiskt bistånd arbetar förebyggande för att motverka att det långvariga biståndstagandet går i socialt arv mellan föräldrar och barn. För att ta reda på detta har vi intervjuat socialsekreterare med erfarenhet och kompetens inom området. Det insamlade materialet har analyserats utifrån den sociala inlärningsteorin som ett försök till att förstå hur det sociala arvet kan föras vidare mellan generationer. Som ett komplement till teorin används även barnperspektivet i analysen då barnen har stor del i studien. Denna studie visar och bekräftar att långvarigt ekonomiskt biståndstagande kan komma att gå i socialt arv mellan föräldrar och barn. Studien visar även på vilket sätt förebyggande arbete för dessa familjer sker på enheten för ekonomiskt bistånd.

Should educational policies be regressive?

In this paper, we show that when the government is able to transfer wealth between generations, regressive policies are no longer optimal. The optimal educational policy can be decentralized through appropriate Pigouvian taxes and credit provision, is not regressive, and provides equality of opportunities in education (in the sense of irrelevance of parental income for the amount of education). Moreover, in the presence of default, the optimal policy can be implemented through income-contingent payments.

A internacionalização da publicidade brasileira - 1970/2002

O processo de globalização da economia tem moldado um cenário complexo e desafiante para o setor publicitário brasileiro. A fusão e incorporação entre agências, com a absorção de muitas por grandes grupos de comunicação, é uma das mais visíveis transformações estruturais desde a década de 1980. O presente estudo investigou as seguintes questões: o impacto da internacionalização da publicidade brasileira nas relações entre as agências, anunciantes e veículos de comunicação; como as agências brasileiras têm ajustado seu modo de operação e competição, visando vantagem competitiva e lucratividade; as alternativas de continuidade das agências brasileiras diante da transmissão do poder aos sucessores legais e das propostas de fusão ou incorporação de grupos estrangeiros. Este estudo se insere na linha de pesquisa "Estudos da Cultura e do Consumo", desenvolvida pelo CECC - Centro de Estudos da Cultura e do Consumo, da EAESP/FGV.

Three essays on education from the perspective of the economics of public setor

This work consists of three essays organized into chapters that seek to answer questions at first sight unrelated, but with one common denominator, which is the scarcity of public resources devoted to education, overall, especially in lower education. . The first chapter deals with the scarcity of resources devoted to education in a context of population aging. Two hypotheses were tested for Brazilian municipalities on the relationship between the aging of the population and educational expenditure. The first, already proven in the literature, is that there is an intergenerational conflict for resources and the increase of the share of elderly in the population reduces the educational expenditure. The second, proposed here for the first time, is that there should be reduction of competition for resources if there is a relationship of co-residence between young and old. The results indicated that an increase in the share of elderly reduces the educational expenditure per youth. But the results also illustrate that an increase in the share of elderly co-residing with youth (family arrangement more common in Latin American countries) raises the educational expenditure, which reflects a reduction of competition for resources between generations. The second chapter assesses the allocative efficiency of investments in Higher Education. Using the difference between first-year and last-year students’ scores from Enade aggregated by HEI as a product in the Stochastic Production Function, is possible to contribute with a new element in the literature aimed at estimating the production function of education. The results show that characteristics of institutions are the variables that best explain the performance of students, and that public institutions are more inefficient than the private ones. Finally, the third chapter presents evidence that the allocation of public resources in early childhood education is important for a better future school performance. In this chapter was calculated the effects of early childhood education on literacy scores of children attending the 2nd grade of elementary school. The results using OLS and propensity score matching show that students who started school at the ages to 5, 4, and 3 years had literacy scores between 12.22 and 19.54 points higher than the scores of those who began school at the ages 6 years or late. The results also suggest that the returns in terms of literacy scores diminish in relation to the number of years of early childhood education.

Essays on industrial organization

Esta tese compõe-se de três ensaios que versam sobre o formato, em termos de estrutura de governança, das indústrias e como a estrutura interna das mesmas in fluenciam esses formatos e seus produtos. O primeiro capítulo apresenta um modelo de como a qualidade institucional, confiança e incompleteza contratual afetam as decisiões das firmas sobre a melhor forma de se organizarem internacionalmente. O segundo capítulo vai na mesma direcão de explicar a organização das indústrias, mas com foco no efeito da transmissão de informação entre as unidades constituintes das organizações sobre o formato ótimo das mesmas. Ambos trabalhos usam modelos dinâmicos. O terceiro capítulo se utiliza da modelagem de organização industrial para mostrar como a estrutura interna de uma indústria in fluencia no risco de crédito consignado.

Public debt and the limits of fiscal policy to increase economic growth

Research that seeks to estimate the effects of fiscal policies on economic growth has ignored the role of public debt in this relationship. This study proposes a theoretical model of endogenous growth, which demonstrates that the level of the public debt-to-gross domestic product (GDP) ratio should negatively impact the effect of fiscal policy on growth. This occurs because government indebtedness extracts part of the savings of the young to pay interest on the debts of the older generation, who are no longer saving. Therefore, the payment of debt interest assumes an allocation exchange role between generations that is similar to a pay-as-you-go pension system, which results in changes in the savings rate of the economy. The major conclusions of the theoretical model were tested using an econometric model to provide evidence for the validity of this conclusion. Our empirical analysis controls for timeinvariant, country-specific heterogeneity in the growth rates. We also address endogeneity issues and allow for heterogeneity across countries in the model parameters and for cross-sectional dependence.

Estudo ergonômico sobre o calor

O calor, no ambiente onde o ser humano vive ou trabalha, atribui-se a: -fatores físicos: relação entre temperatura, radiação, umidade e movimento do ar; fatores humanos: o ser humano atua como fonte de energia através de seu metabolismo e atividade física. o calor caracterizado por um determinado meio ambiente é o resultado da atuação de diferentes variáveis, tais como: sistema de construção, situação geográfica do ambiente físico, climatização artificial, etc.; idade, sexo, capacidade física, estado de aclimatação, vestuário, tipo, carga e regime de trabalho, etc. A partir do momento em que o indivíduo for introduzido num determinado meio ambiente térmico, todos estes fatores vão influenciar a transmissão de calor entre ele e o ambiente. Na pretensão de haver equilíbrio térmico no meio ambiente quente, constata-se a necessidade de providenciar medidas de proteção a nível do sujeito e do ambiente, para que prevaleçam situações ambientais "confortáveis", ou pelo menos, "tolerantes". Desse modo, através da: definição das condições térmicas tolerantes e de conforto, parte-se para projetar meios ambientes de trabalho, que tornem praticáveis um isolamento térmico do calor exterior, assim como a perda de calor de dentro para fora. Atuando-se sobre variáveis individuais e ambientais estaremos incidindo diretamente sobre os meios de transmissão, procurando-se diminuir a quantidade de calor que o organismo produz e/ou recebe e aumentar a possibilidade de dissipá-lo.

Fatores que influenciam a utilização de trading companies nos processos de exportação de empresas brasileiras

O presente estudo procurou identificar quais são os fatores que influenciam a utilização de trading companies nos processos de exportação de empresas brasileiras, tendo como uma das principais justificativas o fato da exportação ser uma das atividades econômicas que apresentam o maior crescimento e contribuição para a economia mundial. O modelo de pesquisa investigou a influência da distância psíquica, distância física, conteúdo de commodity dos produtos exportados, complexidade do ambiente de negócios e risco associado aos países de destino das exportações brasileiras. Serviram como base para a pesquisa a teoria dos custos de transação, estudos relativos aos modos de entrada em mercados internacionais e exportações indiretas. Os testes foram conduzidos a partir de um banco de dados secundários que continha informações relativas às exportações brasileiras realizadas entre os anos de 2006 e 2009, totalizando 450.475 operações. Deste total 80,1% eram exportações diretas e 19.9% exportações indiretas. Os resultados apontam o risco país e a distância psíquica como os fatores que mais influenciam a utilização de trading companies nos processos de exportação das empresas brasileiras. Em relação ao conteúdo de commodity os testes apresentaram resultados parcialmente favoráveis. Conclui-se que quanto maior o risco país e a distância psíquica entre o Brasil e os países de destino das operações de exportação maiores as chances de utilização das trading companies.

Perfil motivacional da geração Y comparado ao de outros grupos etários: investigação em uma instituição financeira nacional

A presente dissertação investiga o perfil motivacional de empregados de uma grande instituição financeira brasileira, inseridos no corte demográfico designado de “Geração Y” (Y’s). Tal perfil foi comparado ao de empregados pertencentes a outros grupos etários da mesma instituição. Para dar suporte à pesquisa, o referencial teórico analisa os cortes geracionais – com enfoque na Geração Y – e diferentes visões sobre o tema da motivação, bem como debate a importância do conhecimento do perfil motivacional desses empregados, para uma adequada formulação de estratégias de motivação laboral. Secundariamente, para essa análise a pesquisa busca auxílio na teoria do contrato psicológico de trabalho. Na coleta de dados da pesquisa foi utilizada a Escala de Valores de Schwartz (Schwartz Value Survey), em sua versão PVQ – Portrait Value Questionnaire, com o objetivo de prescrutar os tipos motivacionais mais relevantes dos Y’s e seus cohorts, permitindo-se, com isso, traçar um perfil motivacional de cada grupo demográfico. Com base na amostra coletada, o estudo conclui que não há evidência sobre a existência de diferenças no perfil motivacional, sob o ponto de vista estatístico, entre os cortes geracionais dentro da organização pesquisada.