Impact of San-mediated Signaling on Glioblastoma and Neuroblastoma Metabolism

Glioblastoma (GBM) is the most common and aggressive type of brain cancer, with an average life expectancy of 15 months. The standard of care for GBM, surgery accompanied by radiation and chemotherapy (temozolomide-TMZ), has not changed in over 10 years illustrating the need for new and efficacious treatments. Therefore, it is imperative to improve our knowledge of GBM physiology to understand the mechanisms driving recurrence and chemoresistance so that more effective therapeutic options can be developed. Mitochondria-cell communication is key to monitor and maintain both mitochondrial and cellular health, and signaling events on the outer mitochondrial membrane (OMM) have emerged as a crucial signal integration site for cellular responses. Consequently, proteins on the OMM are crucial to determining cellular survival and dictating organelle physiology. Thus, the goal of our current study is to evaluate OMM proteins to determine how alterations in organelle regulation may impact CNS tumor biology. We first measured the concentrations of Bcl-2 family proteins on mitochondria from ten continuous GBM cell lines and correlated the protein levels to IC50values of genotoxic agents TMZ and irinotecan. We found that Bcl-2 levels corresponded to chemoresistance, while increased Bim concentrations promoted chemosensitivity. In contrast to our studies in gynecological cancers, the concentrations of the pro-dysfunction OMM scaffold protein Sab had no impact on chemosensitivity of the GBM cell lines, despite diminished Sab expression in GBM patients. However, we identified a novel truncated variant of Sab in the GBM cell lines. We found that GBM cells expressing only full-length Sab had a slower proliferation rate than those with the variant, which could be attributed to increased glycolysis in GBM cells expressing the Sab variant. To determine if the lack of Sab-mediated apoptosis was consistent across CNS tumors, we analyzed publicly-available patient data and found that Sab expression is down-regulated in neuroblastoma patients, a pediatric malignancy responsible for 12% of childhood cancer deaths. We found that that inhibiting Sab-mediated signaling in human neuroblastoma (SH-SY5Y cells) enhanced oxidative phosphorylation in a pyruvate dehydrogenase-dependent manner, increased BCl-2 levels (pro-survival), decreased Bim concentrations (pro-apoptotic), and promoted chemoresistance. Furthermore, examination of additional neuroblastoma cells derived from CNS tumors revealed that Sab levels correspond to proliferation rate, metabolic phenotype, and chemosensitivity. Our studies demonstrate the importance of OMM signaling in CNS tumor physiology and emphasizes the importance of cellular context to the outcomes of OMM signaling events

ENTRE VIDAS NO JORNALISMO LITERÁRIO E ESTUDOS POLÍTICOS: diversidade de olhares na construção da Comunicação

A Revista Observatório apresenta seu sexto número de 2018, com capa produzida pelos colegas do Coletivo Fabulografias (UNICAMP/UNISO), trazendo dois dossiês especiais! O primeiro, intitulado JORNALISMO LITERÁRIO, foi organizado pelos colegas Dra. Monica Martinez, da Universidade de Sorocaba (UNISO) e pelo Dr. Mateus Yuri Passos, Universidade Metodista de São Paulo (UNIMEP) e tem o objetivo de socializar as pesquisas sobre histórias de vida de pesquisadores de Jornalismo Literário. O segundo, intitulado COMUNICAÇÃO, POLÍTICA E AMAZÔNIA, foi organizado pelos colegas Dra. Cynthia Mara Miranda, Universidade Federal do Tocantins (UFT), Dra. Danila Gentil Rodriguez Cal, da Universidade Federal do Pará (UFPA) e Dra. Li-Chang Shuen, da Universidade Federal do Maranhão (UFMA) e  tem como foco trazer artigos que versem sobre as relações de Comunicação e Política no contexto da Amazônia Legal como estudos realizados por pesquisadores (as) que estão vinculados a instituições de ensino e pesquisa sediados na região e que pesquisam Comunicação e Política

Incidence and clearance of anal high-risk human papillomavirus in HIV-positive men who have sex with men: Estimates and risk factors

Background: To estimate incidence and clearance of high-risk human papillomavirus (HR-HPV), and their risk factors, in men who have sex with men (MSM) recently infected by HIV in Spain; 2007-2013. Methods: Multicenter cohort. HR-HPV infection was determined and genotyped with linear array. Two-state Markov models and Poisson regression were used. Results: We analysed 1570 HR-HPV measurements of 612 MSM over 13 608 person-months (p-m) of follow-up. Median (mean) number of measurements was 2 (2.6), median time interval between measurements was 1.1 years (interquartile range: 0.89-1.4). Incidence ranged from 9.0 [95% confidence interval (CI) 6.8-11.8] per 1000 p-m for HPV59 to 15.9 (11.7-21.8) per 1000 p-m for HPV51. HPV16 and HPV18 had slightly above average incidence: 11.9/1000 p-m and 12.8/1000 p-m. HPV16 showed the lowest clearance for both 'prevalent positive' (15.7/1000 p-m; 95% CI 12.0-20.5) and 'incident positive' infections (22.1/1000 p-m; 95% CI 11.8-41.1). More sexual partners increased HR-HPV incidence, although it was not statistically significant. Age had a strong effect on clearance (P-value < 0.001) due to the elevated rate in MSM under age 25; the effect of HIV-RNA viral load was more gradual, with clearance rate decreasing at higher HIV-RNA viral load (P-value 0.008). Conclusion: No large variation in incidence by HR-HPV type was seen. The most common incident types were HPV51, HPV52, HPV31, HPV18 and HPV16. No major variation in clearance by type was observed, with the exception of HPV16 which had the highest persistence and potentially, the strongest oncogenic capacity. Those aged below 25 or with low HIV-RNA- viral load had the highest clearanceThis work was supported by grants from the Fondo de Investigacio´n Sanitaria [PI06/0372, PS09/2181], Red de Investigacio´n en SIDA (RIS) [RD06/006/0026 and RD12/0017/0018 to C.G.] and CIBERESP [group 54A-CB06/02/1009

First Colombian Multicentric Newborn Screening for Congenital Toxoplasmosis

Congenital toxoplasmosis can result in permanent sequel as blindness or neurological damage in children and it seems to be more severe in South America than in other continents. There is a lack of information about this frequency in Colombia, where no control program is established, although it is a recognized cause of potentially preventable congenital blindness. We propose the first Colombian multicentric study to determine the frequency and impact of congenital toxoplasmosis. More than 15,000 newborns in seven cities were studied. Newborns were tested at birth by doing a cord blood test for toxoplasmosis. Additionally, children from mothers with history of toxoplasmosis acquired during pregnancy were recalled for a follow-up. The program identified fifteen children otherwise undiagnosed; three of these children died as consequence of congenital toxoplasmosis. The frequency of the congenital infection varied significantly between cities, being higher in Armenia and Florencia, intermediate in Bogota, Bucaramanga and Barranquilla and very low in western cities such as Cucuta and Riohacha. For the first time a significant correlation was found between mean rainfall at the city and the incidence of this congenital infection

Recuperación monumental ambiental de la Alameda Central de la Ciudad de México

752 páginas. Especialización en Diseño.El presente trabajo se centra en el estudio, análisis y rescate de la Alameda Central de la Ciudad de México, la cual se sitúa hoy en el corazón de la gran ciudad, siendo ésta el paseo más antiguo de América y lugar que ha visto acontecer los cambios políticos, sociales y culturales de una nación, que es hoy México. El estudio es una recopilación cronológica de los sucesos que dieron origen al primer parque público de México, así como su desarrollo y los cambios morfológicos que ha presentado a lo largo de los años, lo que le otorga un carácter relevante y lo define como el paseo más importante del país

Brettanomyces bruxellensis yeasts: impact on wine and winemaking

Yeasts belonging to the Brettanomyces/Dekkera genus are non-conventional yeasts, which affect winemaking by causing wine spoilage all over the world. This mini-review focuses on recent results concerning the presence of Brettanomyces bruxellensis throughout the wine processing chain. Here, culture-dependent and independent methods to detect this yeast on grapes and at the very early stage of wine production are encompassed. Chemical, physical and biological tools, devised for the prevention and control of such a detrimental species during winemaking are also presented. Finally, the mini-review identifies future research areas relevant to the improvement of wine safety and sensory profiles

SmokeHaz: systematic reviews and meta-analyses of the effects of smoking on respiratory health

Background: Smoking tobacco increases the risk of respiratory disease in adults and children, but communicating the magnitude of these effects in a scientific manner that is accessible and usable by public and policymakers presents a challenge. We have therefore summarised scientific data on the impact of smoking on respiratory diseases to provide the content for a unique resource, SmokeHaz. Methods: We conducted systematic reviews and meta-analyses of longitudinal studies (published to 2013) identified from electronic databases, grey literature, and experts. Random effect meta-analyses were used to pool the findings. Results: We included 216 papers. Among adult smokers, we confirmed substantially increased risks of lung cancer (Risk Ratio (RR) 10.92, 95% CI 8.28-14.40; 34 studies), COPD (RR 4.01, 95% CI 3.18-5.05; 22 studies) and asthma (RR 1.61, 95% CI 1.07-2.42; 8 studies). Exposure to passive smoke significantly increased the risk of lung cancer in adult non-smokers; and increased the risks of asthma, wheeze, lower respiratory infections, and reduced lung function in children. Smoking significantly increased the risk of sleep apnoea, and asthma exacerbations in adult and pregnant populations; and active and passive smoking increased the risk of tuberculosis. Conclusions: These findings have been translated into easily digestible content and published on the SmokeHaz website (www.smokehaz.eu)

Progressive skin fibrosis is associated with a decline in lung function and worse survival in patients with diffuse cutaneous systemic sclerosis in the European Scleroderma Trials and Research (EUSTAR) cohort.

Objectives To determine whether progressive skin fibrosis is associated with visceral organ progression and mortality during follow-up in patients with diffuse cutaneous systemic sclerosis (dcSSc). Methods We evaluated patients from the European Scleroderma Trials and Research database with dcSSc, baseline modified Rodnan skin score (mRSS) ≥7, valid mRSS at 12±3 months after baseline and ≥1 annual follow-up visit. Progressive skin fibrosis was defined as an increase in mRSS &gt;5 and ≥25% from baseline to 12±3 months. Outcomes were pulmonary, cardiovascular and renal progression, and all-cause death. Associations between skin progression and outcomes were evaluated by Kaplan-Meier survival analysis and multivariable Cox regression. Results Of 1021 included patients, 78 (7.6%) had progressive skin fibrosis (skin progressors). Median follow-up was 3.4 years. Survival analyses indicated that skin progressors had a significantly higher probability of FVC decline ≥10% (53.6% vs 34.4%; p&lt;0.001) and all-cause death (15.4% vs 7.3%; p=0.003) than non-progressors. These significant associations were also found in subgroup analyses of patients with either low baseline mRSS (≤22/51) or short disease duration (≤15 months). In multivariable analyses, skin progression within 1 year was independently associated with FVC decline ≥10% (HR 1.79, 95% CI 1.20 to 2.65) and all-cause death (HR 2.58, 95% CI 1.31 to 5.09). Conclusions Progressive skin fibrosis within 1 year is associated with decline in lung function and worse survival in dcSSc during follow-up. These results confirm mRSS as a surrogate marker in dcSSc, which will be helpful for cohort enrichment in future trials and risk stratification in clinical practice