Dengue-induced autophagy, virus replication and protection from cell death require ER stress (PERK) pathway activation

Avirus that reproduces in a host without killing cells can easily establish a successful infection. Previously, we showed that dengue-2, a virus that threatens 40% of the world, induces autophagy, enabling dengue to reproduce in cells without triggering cell death. Autophagy further protects the virus-laden cells from further insults. In this study, we evaluate how it does so; we show that dengue upregulates host pathways that increase autophagy, namely endoplasmic reticulum (ER) stress and ataxia telangiectasiamutated (ATM) signaling followed by production of reactive oxygen species (ROS). Inhibition of ER stress or ATM signaling abrogates the dengueconferred protection against other cell stressors. Direct inhibition of ER stress response in infected cells decreases autophagosome turnover, reduces ROS production and limits reproduction of dengue virus. Blocking ATM activation, which is an early response to infection, decreases transcription of ER stress response proteins, but ATM has limited impact on production of ROS and virus titers. Production of ROS determines only late-onset autophagy in infected cells and is not necessary for dengue-induced protection from stressors. Collectively, these results demonstrate that among the multiple autophagy-inducing pathways during infection, ER stress signaling is more important to viral replication and protection of cells than either ATM or ROS-mediated signaling. To limit virus production and survival of dengue-infected cells, one must address the earliest phase of autophagy, induced by ER stress

Social roles and aging from a life-span perspective

Este trabalho investigou os papéis sociais e as tarefas evolutivas desempenhados por adultos. O local escolhido para investigação foi um assentamento de famílias de baixa renda do Distrito Federal criado em 1989. Utilizou-se um questionário contendo 17 questões abertas e 15 questões fechadas, preenchido pela primeira autora durante uma visita domiciliar. Participaram 98 respondentes (73 F e 25 M), sendo 51 entre 50 e 59 anos e 47 a partir de 60 anos. Os resultados apontaram que este grupo é heterogêneo e que seus papéis sociais são influenciados pelas variáveis demográficas (idade, sexo, escolaridade, ocupação, naturalidade e estado civil) e também pelas variáveis relativas à moradia atual. Concluiu-se também que as expectativas sociais, o suporte social e a escolarização são fatores de suma importância para oferecer recursos para a otimização e compensação necessárias a um envelhecimento bem sucedido. __________________________________________________________________________________________________________ ABSTRACTThis study investigated the social roles and developmental tasks of adults. The study took place in a settlement of low-income families, created in The Federal District in 1989. Data were collected through a questionnaire composed of 17 open and 15 closed questions, administered by the first author during a home visit. There were 98 respondents, 73 female and 25 male, being 51 between 50 to 59 years old and 47 elders above the age of 60. The result indicated that this group is heterogeneous and that its social roles are influenced by the demographic variables - age, sex, educational level, work, place of the birth and marital status, as well for the relative variables to current residence. The data allow the conclusion that social expectations, social support and the educational level are important resources for the optimization and necessary compensation to successful aging

Feeling older and wanting to be younger

Two samples of middle-aged women were compared using a questionnaire adapted from Rossi (1980). One sample ( N = 20) consisted of women who felt older than and desired to be younger than their own age. The second sample ( N = 19) was comprised of women who felt and desired to be their own age. Statistically significant differences between the groups were that women who felt older reported more physical changes of aging, less satisfaction with their life context, and more worries than the women who felt their chronological age. Results of this study suggest that current life stress contributes to middle-aged women's perceptions of feeling older and desiring to be younger than their own age.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42987/1/10823_2004_Article_BF00116678.pd

Lack of Bax Prevents Influenza A Virus-Induced Apoptosis and Causes Diminished Viral Replication ▿

The ectopic overexpression of Bcl-2 restricts both influenza A virus-induced apoptosis and influenza A virus replication in MDCK cells, thus suggesting a role for Bcl-2 family members during infection. Here we report that influenza A virus cannot establish an apoptotic response without functional Bax, a downstream target of Bcl-2, and that both Bax and Bak are directly involved in influenza A virus replication and virus-induced cell death. Bak is substantially downregulated during influenza A virus infection in MDCK cells, and the knockout of Bak in mouse embryonic fibroblasts yields a dramatic rise in the rate of apoptotic death and a corresponding increase in levels of virus replication, suggesting that Bak suppresses both apoptosis and the replication of virus and that the virus suppresses Bak. Bax, however, is activated and translocates from the cytosol to the mitochondria; this activation is required for the efficient induction of apoptosis and virus replication. The knockout of Bax in mouse embryonic fibroblasts blocks the induction of apoptosis, restricts the infection-mediated activation of executioner caspases, and inhibits virus propagation. Bax knockout cells still die but by an alternative death pathway displaying characteristics of autophagy, similarly to our previous observation that influenza A virus infection in the presence of a pancaspase inhibitor leads to an increase in levels of autophagy. The knockout of Bax causes a retention of influenza A virus NP within the nucleus. We conclude that the cell and virus struggle to control apoptosis and autophagy, as appropriately timed apoptosis is important for the replication of influenza A virus

Ancient jades map 3,000 years of prehistoric exchange in Southeast Asia

We have used electron probe microanalysis to examine Southeast Asian nephrite (jade) artifacts, many archeologically excavated, dating from 3000 B.C. through the first millennium A.D. The research has revealed the existence of one of the most extensive sea-based trade networks of a single geological material in the prehistoric world. Green nephrite from a source in eastern Taiwan was used to make two very specific forms of ear pendant that were distributed, between 500 B.C. and 500 A.D., through the Philippines, East Malaysia, southern Vietnam, and peninsular Thailand, forming a 3,000-km-diameter halo around the southern and eastern coastlines of the South China Sea. Other Taiwan nephrite artifacts, especially beads and bracelets, were distributed earlier during Neolithic times throughout Taiwan and from Taiwan into the Philippines