Oncogenic Gain of Function in Glioblastoma Is Linked to Mutant p53 Amyloid Oligomers.

Tumor-associated p53 mutations endow cells with malignant phenotypes, including chemoresistance. Amyloid-like oligomers of mutant p53 transform this tumor suppressor into an oncogene. However, the composition and distribution of mutant p53 oligomers are unknown and the mechanism involved in the conversion is sparse. Here, we report accumulation of a p53 mutant within amyloid-like p53 oligomers in glioblastoma-derived cells presenting a chemoresistant gain-of-function phenotype. Statistical analysis from fluorescence fluctuation spectroscopy, pressure-induced measurements, and thioflavin T kinetics demonstrates the distribution of oligomers larger than the active tetrameric form of p53 in the nuclei of living cells and the destabilization of native-drifted p53 species that become amyloid. Collectively, these results provide insights into the role of amyloid-like mutant p53 oligomers in the chemoresistance phenotype of malignant and invasive brain tumors and shed light on therapeutic options to avert cancer

Phenolic compounds accumulation in soybean plants in response to Phakopsora pachyrhizi.

Asian soybean rust (ASR) is a soybean disease caused by Phakopsora pachyrhizi Sydow. The phenylpropanoid pathway is involved in many biological processes including the defense response to the fungus. This pathway results in the production of lignin and phytoalexins, which are an important defense against pathogens and insects. In the present work, we used high performance liquid chromatography (HPLC) to measure the production of compounds in the phenylpropanoid pathway in leaves of the resistant soybean genotype (PI459025B, Rpp4). Plants were either infected with P. pachyrhizi or mock infected with water, and leaf tissue was collected at 24, 48, 72, 96, 120, 161, 308 and 504 hours after inoculation (hai). Phenolic peak quantification was carried out by estimating the area of each detected peak from all wavelengths or their relative proportion compared to the estimated total phenolic level. ANOVA analysis followed by Tukey?s Honestly Significant Difference test was used to identify significant differences (P<.05) between treatments and time points. This study allowed identification of the conjugated isoflavones daidzin, malonyl daidzin and malonyl genistin and the isoflavones dadzein and glycitein. In addition, we identified several phenolic acids including caffeic acid, p-coumaric acid, ferulic acid and salicylic acid. The present study revealed many quantitative changes in the soluble phenolic profile of soybean in response to fungus inoculation and the accumulation of specific compounds varied over the infection time course

WHO draft guidelines on dietary saturated and trans fatty acids: time for a new approach?

The 2018 WHO draft guidelines on dietary saturated fatty acids and trans fatty acids recommend reducing total intake of saturated fat and replacing it with polyunsaturated and monounsaturated fatty acids. The recommendations fail to take into account considerable evidence that the health effects of saturated fat varies depending on the specific fatty acid and on the specific food source. Maintaining general advice to reduce total saturated fatty acids will work against the intentions of the guidelines and weaken their effect on chronic disease incidence and mortality. A food based translation of the recommendations for saturated fat intake would avoid unnecessary reduction or exclusion of foods that are key sources of important nutrients

PARP inhibitor efficacy depends on CD8+ T cell recruitment via intratumoral STING pathway activation in BRCA-deficient models of triple-negative breast cancer.

Combinatorial clinical trials of PARP inhibitors with immunotherapies are ongoing, yet the immunomodulatory effects of PARP inhibition have been incompletely studied. Here, we sought to dissect the mechanisms underlying PARP inhibitor-induced changes in the tumor microenvironment of BRCA1-deficient triple-negative breast cancer (TNBC). We demonstrate that the PARP inhibitor olaparib induces CD8+ T cell infiltration and activation in vivo, and that CD8+ T cell depletion severely compromises anti-tumor efficacy. Olaparib-induced T cell recruitment is mediated through activation of the cGAS/STING pathway in tumor cells with paracrine activation of dendritic cells and is more pronounced in HR-deficient compared to HR-proficient TNBC cells and in vivo models. CRISPR-knockout of STING in cancer cells prevents proinflammatory signaling and is sufficient to abolish olaparib-induced T cell infiltration in vivo. These findings elucidate an additional mechanism of action of PARP inhibitors and provide rationale for combining PARP inhibition with immunotherapies for the treatment of TNBC

Perfil da mortalidade infantil em Petrolina (PE) entre os anos de 1994 a 2005

Infant mortality is a public health problem that has experienced reductions in recent years in Brazil, due to better conditions of life and investments to promote maternal and child health. The aim of this study was to evaluate the profile of infant mortality in Petrolina-PE, between the years 1994 to 2005. There has been research that are descriptive and quantitative, using indicators of live births and infant mortality, describing the profile of infant mortality in Petrolina. We applied the system DATASUS for data collection, and the income was through graphs and tables. In the data analysis, we observed that, in Petrolina over the 12 years studied was an average of 25 infant deaths per thousand live births. In an attempt to minimize the mortality public health policies need to be more effective actions, with focus to education in maternal and child health, and invest in the achievement of pre-natal to better quality.A mortalidade infantil é um problema de saúde pública que vem sofrendo reduções nos últimos anos no Brasil, devido às melhores condições de vida da população e investimentos de promoção à saúde materno-infantil. O objetivo deste estudo foi avaliar o perfil da mortalidade infantil em Petrolina (PE), entre os anos de 1994 a 2005. Foi desenvolvida uma pesquisa de caráter descritivo e quantitativo, utilizando-se os indicadores de nascidos vivos e mortalidade infantil e descrevendo-se o perfil da mortalidade infantil em Petrolina. Empregou-se o sistema DATASUS para a coleta de dados, e a demonstração dos resultados ocorreu através de gráficos e tabelas. Na análise dos dados, observou-se que, em Petrolina, durante os 12 anos estudados, ocorreu uma média de 25 mortes infantis por mil nascidos vivos. Na tentativa de minimizar a mortalidade infantil, as políticas públicas de saúde necessitam de ações mais efetivas, com enfoque para a educação em saúde materno-infantil, além de investimentos na realização de um pré-natal de melhor qualidade

Aspectos clínicos de pacientes acometidos com asma brônquica / Clinical aspects of patients affected with bronchic asthma

Introdução: A asma é caracterizada por uma obstrução variável das vias aéreas inferiores e hiper-responsividade brônquica, isto é, uma resposta imunológica demasiada ao estimulo que seria inofensivo em pessoas normais, de caráter progressivo e degenerativo, e sem cura definitiva. (MOURA; CAMARGO; BLIC, 2002). Objetivos: Descrever de maneira sucinta o mecanismo de ação da asma no organismo. Metodologia: Foi realizada a seleção de material para leitura através de plataformas on line e literatura física, a qual delineou os aspectos a serem abordados na pesquisa. Resultados e Discussão: A pessoa acometida pela asma brônquica não precisa parar de realizar suas atividades de vida diária, ao ser diagnosticada se traçará uma linha de cuidados para que a mesma possa ser tratada, melhorando o seu condicionamento e qualidade de vida, evitando assim a ida constante a emergências. Considerações Finais: Verificou – se a necessidade de novos estudos na abordagem de terapias alternativas não farmacológicas para asma, pois estes ainda são escassos; os envolvidos devem ser orientados quanto as possibilidades de tratamento e cuidados a serem tomados para uma melhor obtenção de resultados e aceitação

Malaria in Kakuma refugee camp, Turkana, Kenya: facilitation of Anopheles arabiensis vector populations by installed water distribution and catchment systems

<p>Abstract</p> <p>Background</p> <p>Malaria is a major health concern for displaced persons occupying refugee camps in sub-Saharan Africa, yet there is little information on the incidence of infection and nature of transmission in these settings. Kakuma Refugee Camp, located in a dry area of north-western Kenya, has hosted ca. 60,000 to 90,000 refugees since 1992, primarily from Sudan and Somalia. The purpose of this study was to investigate malaria prevalence and attack rate and sources of <it>Anopheles </it>vectors in Kakuma refugee camp, in 2005-2006, after a malaria epidemic was observed by staff at camp clinics.</p> <p>Methods</p> <p>Malaria prevalence and attack rate was estimated from cases of fever presenting to camp clinics and the hospital in August 2005, using rapid diagnostic tests and microscopy of blood smears. Larval habitats of vectors were sampled and mapped. Houses were sampled for adult vectors using the pyrethrum knockdown spray method, and mapped. Vectors were identified to species level and their infection with <it>Plasmodium falciparum </it>determined.</p> <p>Results</p> <p>Prevalence of febrile illness with <it>P. falciparum </it>was highest among the 5 to 17 year olds (62.4%) while malaria attack rate was highest among the two to 4 year olds (5.2/1,000/day). Infected individuals were spatially concentrated in three of the 11 residential zones of the camp. The indoor densities of <it>Anopheles arabiensis</it>, the sole malaria vector, were similar during the wet and dry seasons, but were distributed in an aggregated fashion and predominantly in the same zones where malaria attack rates were high. Larval habitats and larval populations were also concentrated in these zones. Larval habitats were man-made pits of water associated with tap-stands installed as the water delivery system to residents with year round availability in the camp. Three percent of <it>A. arabiensis </it>adult females were infected with <it>P. falciparum </it>sporozoites in the rainy season.</p> <p>Conclusions</p> <p>Malaria in Kakuma refugee camp was due mainly to infection with <it>P. falciparum </it>and showed a hyperendemic age-prevalence profile, in an area with otherwise low risk of malaria given prevailing climate. Transmission was sustained by <it>A. arabiensis</it>, whose populations were facilitated by installation of man-made water distribution and catchment systems.</p