Replication stress and chromatin context link ATM activation to a role in DNA replication

ATM-mediated signaling in response to DNA damage is a barrier to tumorigenesis. Here we asked whether replication stress could also contribute to ATM signaling. We demonstrate that, in the absence of DNA damage, ATM responds to replication stress in a hypoxia-induced heterochromatin-like context. In certain hypoxic conditions, replication stress occurs in the absence of detectable DNA damage. Hypoxia also induces H3K9me3, a histone modification associated with gene repression and heterochromatin. Hypoxia-induced replication stress together with increased H3K9me3 leads to ATM activation. Importantly, ATM prevents the accumulation of DNA damage in hypoxia. Most significantly, we describe a stress-specific role for ATM in maintaining DNA replication rates in a background of increased H3K9me3. Furthermore, the ATM-mediated response to oncogene-induced replication stress is enhanced in hypoxic conditions. Together, these data indicate that hypoxia plays a critical role in the activation of the DNA damage response, therefore contributing to this barrier to tumorigenesis

HIF-1 alpha-independent hypoxia-induced rapid PTK6 stabilization is associated with increased motility and invasion

© 2014 Landes Bioscience. PTK6/Brk is a non-receptor tyrosine kinase overexpressed in cancer. Here we demonstrate that cytosolic PTK6 is rapidly and robustly induced in response to hypoxic conditions in a HIF-1-independent manner. Furthermore, a proportion of hypoxic PTK6 subsequently re-localized to the cell membrane. We observed that the rapid stabilization of PTK6 is associated with a decrease in PTK6 ubiquitylation and we have identified c-Cbl as a putative PTK6 E3 ligase in normoxia. The consequences of hypoxia-induced PTK6 stabilization and subcellular re-localization to the plasma membrane include increased cell motility and invasion, suggesting PTK6 targeting as a therapeutic approach to reduce hypoxia-regulated metastatic potential. This could have particular significance for breast cancer patients with triple negative disease

Produção de frutos de pedra-ume-caá em função de condições meteorológicas em Manaus-AM.

O objetivo do presente trabalho foi avaliar o comportamento da produção de frutos de pedra-ume-caá, espécie medicinal amazônica, em função das variações das condições meteorológicas em Manaus-AM

The impact of social risk in a paediatric department

Introdução: Os maus tratos a crianças correspondem a qualquer acção ou omissão não acidental, que ameace a sua segurança, dignidade e correcto desenvolvimento biopsicossocial. Pretendeu-se avaliar o seu impacto no internamento de Pediatria. Metodologia: Estudo retrospectivo dos doentes internados no Serviço de Pediatria de um hospital terciário entre 1/10/10 e 30/09/11, sinalizados ao Núcleo Hospitalar de Apoio a Crianças e Jovens em Risco (NHACJR). Foi considerada alta clínica o momento em que o doente já não apresentava critérios clínicos para o internamento. Na avaliação do impacto económico foi considerado o valor do custo diário de assistência hospitalar (85,00€) referido no DR 1ªsérie, de Janeiro de 2009. Resultados: Num total de 1052 internamentos, foi solicitada avaliação ao NHACJR em 4,1% (43) dos episódios. Os lactentes representaram 53,5% das sinalizações. O desemprego verificou-se em 66% dos pais e 37,2% destes tinham completadoo 3º ciclo de ensino básico. O modelo de família nuclear foi identificado em 37,2% dos casos. A presença de indicadores de risco social sem evidência aparente de maus tratos ocorreu em 48,8%. A negligência foi identificada em 39,5% das crianças, seguida dos maus tratos físicos com 6,9%. Quatro internamentos foram por motivos exclusivamente sociais, com um tempo médio de internamento de 10,5 dias. Dez crianças com critérios clínicos de internamento vieram a ter adiamento da alta hospitalar por motivos sociais, com um prolongamento médio do tempo de internamento de 33,2 dias. Neste grupo de catorze casos ocorreram seis infecções nosocomiais, um traumatismo crânio-encefálico e o custo adicional estimado de assistência hospitalar foi de 31.790,00€. Comentários: O impacto das razões sociais no internamento em Pediatria não é negligenciável quer do ponto de vista clínico quer económico. Uma reflexão multidisciplinar sobre a necessidade de maior apoio social na comunidade revela-se necessária, tendo por base os direitos da criança hospitalizada e o contexto socioeconómico actual

Ghrelin requires p53 to stimulate lipid storage in fat and liver

Ghrelin, a stomach-derived peptide, stimulates feeding behavior and adiposity. For its orexigenic action, ghrelin triggers a central SIRT1/p53/AMPK pathway. The tumor suppressor p53 also plays an important role in white adipose tissue (WAT), where it is up-regulated in the adipocytes of obese mice. It is not known, however, whether p53 has any role in mediating the peripheral action of ghrelin. In the present study, chronic peripheral ghrelin treatment resulted in increased body weight and fat-mass gain in wild-type mice. Correspondingly, mRNA levels of several adipogenic and fat-storage-promoting enzymes were up-regulated in WAT, whereas hepatic triglyceride content and lipogenic enzymes were also increased in wild-type mice following ghrelin treatment. In contrast, mice lacking p53 failed to respond to ghrelin treatment, with their body weight, fat mass, and adipocyte and hepatic metabolism remaining unchanged. Thus, our results show that p53 is necessary for the actions of ghrelin on WAT and liver, leading to changes in expression levels of lipogenic and adipogenic genes, and modifying body weight

Efficiency of Agricultural Upgrading as a Component of the Farming Extension System

Evaluation was effected through a participative-diagnosis  tool which integrates several techniques and the organ- izational work for agro producer training. Three participative exercises, i.e., brainstorming, questions, and the nine- square or the General Electric matrix, were performed. Deficiencies in the training process and how to solve them, the need of team work to diagnose demands, problems, program design, and program application were determined. Besides, the current situation of the School of Training for Agricultural Executives, affiliated to the Ministry of Ag- riculture division in Camagüey, was assessed, for capital and resource investment, and for introduction of new agro- products and services to the market

Annual Behavior of Milk Production Bio economic Indicators in Dairies of Ruta InvasoraCattle Raising Enterprise, Ciego de Ávila. II. Case Study Dairy.

Previous research of ten dairies at Ruta Invasora Cattle Raising Enterprise, in Ciego de Ávila, about the annual behavior of bioeconomic indicators of milk production singled out Dairy No. 1 as the most outstanding. It was then used as a comparison model in a case study, with the remaining nine units, based on the average reproductive, productive and economic indicators for the five-year period studied. Decomposition of seasonal time series to determine birth behavior was performed, using a multiplication model, considering 10 % above or below 100 %. Dairy No. 1 had birth peaks in the April-July period, with the highest values in May, which seemed to have determined a better behavior, especially in its best year, in relation with reproductive efficiency (78 % birth rate); productive, (1 393 kg/ha); and economic (0.86 CUP/kg of milk), in comparison with the rest of the units and the means from the years studied. These results corroborate the feasibility of improving milk production efficiency when the birth peaks occur within the rainy season