Computing effective tax rates on factor incomes and consumption An international macroeconomic perspective

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Chemical Screening Identifies Enhancers of Mutant Oligodendrocyte Survival and Unmasks a Distinct Pathological Phase in Pelizaeus-Merzbacher Disease

Summary: Pelizaeus-Merzbacher disease (PMD) is a fatal X-linked disorder caused by loss of myelinating oligodendrocytes and consequent hypomyelination. The underlying cellular and molecular dysfunctions are not fully defined, but therapeutic enhancement of oligodendrocyte survival could restore functional myelination in patients. Here we generated pure, scalable quantities of induced pluripotent stem cell-derived oligodendrocyte progenitor cells (OPCs) from a severe mouse model of PMD, Plp1jimpy. Temporal phenotypic and transcriptomic studies defined an early pathological window characterized by endoplasmic reticulum (ER) stress and cell death as OPCs exit their progenitor state. High-throughput phenotypic screening identified a compound, Ro 25–6981, which modulates the ER stress response and rescues mutant oligodendrocyte survival in jimpy, in vitro and in vivo, and in human PMD oligocortical spheroids. Surprisingly, increasing oligodendrocyte survival did not restore subsequent myelination, revealing a second pathological phase. Collectively, our work shows that PMD oligodendrocyte loss can be rescued pharmacologically and defines a need for multifactorial intervention to restore myelination. : Tesar and colleagues interrogate the severe genetic myelin disorder Pelizaeus-Merzbacher disease (PMD) using iPSC-derived oligodendrocyte progenitor cells (OPCs). Using high-throughput phenotypic screening, they rescue cell death of mutant oligodendrocytes immediately after initiation of differentiation with chemical modulators, including Ro 25–6981. Interestingly oligodendrocyte restoration did not lead to widespread myelination, unmasking a new phase of the disease. Keywords: iPSC disease modeling, high-throughput screening, oligodendrocyte progenitor cells, oligodendrocytes, myelin, Pelizaeus-Merzbacher disease, proteolipid protein 1, endoplasmic reticulum stress, PLP1, rare diseas

Determinantes do fluxo de investimentos de portfólio para o mercado acionário brasileiro

Este artigo estuda como os fluxos de investimento para o mercado acionário brasileiro são afetados pelo retorno do índice Ibovespa, variação cambial, taxa SELIC e risco país. São utilizados dados mensais para o período entre 1995 e 2005 e verificadas as relações de causalidade e exogeneidade. Os resultados apontam para o comportamento racional do investidor estrangeiro, entrando no mercado após quedas e saindo após elevações. Os retornos defasados influenciam o fluxo. Há diminuição da posição do investidor estrangeiro quando a moeda doméstica se valoriza em relação ao dólar. A crise cambial de janeiro de 1999 afetou negativamente o investimento. A melhoria do indicador de risco país incentiva a entrada de investimentos. Os fluxos estão relacionados à taxa SELIC, que influencia a formação de expectativas. O índice de Sharpe positivo mostra que o maior risco do mercado brasileiro é compensado por maior rendimento. Após diversos testes diagnósticos, constata-se que o modelo proposto é adequado para inferência, mas não para a formulação de políticas e realização de previsões.<br>This work investigates the effects of equity returns, exchange rates, interest rates and a country risk measure on foreign portfolio investment flows to the Brazilian equity market. Data is monthly from 1995 to 2005. Causality and exogeneity relations are tested. The results point out the rational behavior of foreign investors, who enter the market after a fall and withdraw after a rise of the Bovespa index. Past returns are found to be important in the investment decision. When the domestic currency appreciates in face to the US dollar, foreign investors reduce their exposure to the Brazilian market. The evidence also indicates the exchange crises of January 1999 affected foreign investment. Inflows of investments are stimulated by better external debt evaluation and are also related to the Brazilian interest rate. The Sharpe ratio shows that the higher risk of the Brazilian market is rewarded by higher return. After several diagnostic tests, the model proposed is found to be appropriate for inference use, but not for prediction or policy purposes