Microenvironment involved in FPR1 expression by human glioblastomas

Formyl peptide receptor 1 (FPR1) activity in U87 glioblastoma (GBM) cells contributes to tumor cell motility. The present study aimed to evaluate the FPR1 expression in human GBM, the possibility to elicit agonist induced FPR1 activation of GBM cells and inhibit this activation with chemotaxis inhibitory protein of Staphylococcus aureus (CHIPS). Immunohistochemistry was used to assess FPR1 expression in GBM patient samples, which was present in all 178 samples. Also FPR1 mRNA levels measured with quantitative PCR, could be detected in all 25 GBM patient samples tested. Activation of FPR1 in U87 cells, as measured by human mitochondrial-derived agonists, increased calcium mobilization, AKT and ERK1/2 phosphorylation, and ligand-induced migration. Inhibition of all responses could be achieved with CHIPS. Eight early passage human Groningen Glioma (GG) cell lines, isolated from primary GBM tissue were screened for the presence of FPR1. FPR1 mRNA and protein expression as well as receptor activation could not be detected in any of these early passage GG cell lines. However FPR1 was present in ex vivo tumors formed by the same GG cell lines after being implanted in mouse brains. FPR1 is highly expressed in human GBM specimens, it can be activated by human mitochondrial-derived agonists in U87 and inhibited with CHIPS. FPR1 cannot be detected in early passage GG cell lines in vitro, however when engrafted in the mouse brain these cells show FPR1 expression. These results suggest a role of the brain microenvironment in FPR1 expression in GBM.</p

Adjusted Light and Dark Cycles Can Optimize Photosynthetic Efficiency in Algae Growing in Photobioreactors

Biofuels from algae are highly interesting as renewable energy sources to replace, at least partially, fossil fuels, but great research efforts are still needed to optimize growth parameters to develop competitive large-scale cultivation systems. One factor with a seminal influence on productivity is light availability. Light energy fully supports algal growth, but it leads to oxidative stress if illumination is in excess. In this work, the influence of light intensity on the growth and lipid productivity of Nannochloropsis salina was investigated in a flat-bed photobioreactor designed to minimize cells self-shading. The influence of various light intensities was studied with both continuous illumination and alternation of light and dark cycles at various frequencies, which mimic illumination variations in a photobioreactor due to mixing. Results show that Nannochloropsis can efficiently exploit even very intense light, provided that dark cycles occur to allow for re-oxidation of the electron transporters of the photosynthetic apparatus. If alternation of light and dark is not optimal, algae undergo radiation damage and photosynthetic productivity is greatly reduced. Our results demonstrate that, in a photobioreactor for the cultivation of algae, optimizing mixing is essential in order to ensure that the algae exploit light energy efficiently

Determining of the profile of patients and evaluation of treatment of latent tuberculosis infection in candidates for the use of tumor necrosis factor-alpha blockers in University Hospital Walter CantÃdio (HUWC/UFC).

nÃo hÃA introduÃÃo na prÃtica clÃnica dos agentes bloqueadores do TNF-&#945; representou uma revoluÃÃo no tratamento das doenÃas inflamatÃrias crÃnicas: artrite reumatÃide (AR), espondilite anquilosante (EA), doenÃa de Crohn (DC) e psorÃase. Desde entÃo, seu uso tem sido ampliado, contudo essa terapia de alto custo econÃmico elevou o risco de desenvolvimento das doenÃas infecciosas entre elas, à tuberculose (TB). Por este motivo recomenda-se a investigaÃÃo da Tuberculose latente (TBL) antes do inÃcio da terapÃutica com os bloqueadores do TNF-&#945;. O objetivo do nosso estudo foi traÃar o perfil clÃnico-epidemiolÃgico dos pacientes nessa condiÃÃo clÃnica e avaliar os desfechos de tratamento de pacientes submetidos ao tratamento da TBL por indicaÃÃo do uso de bloqueadores do TNF-&#945; no AmbulatÃrio de Tisiologia do Hospital UniversitÃrio Walter CantÃdeo (HUWC/UFC). MÃtodo: Foi realizada no perÃodo de 2008-2009 uma anÃlise descritiva prospectiva desse grupo de pacientes seguido de um estudo analÃtico observacional do tipo transversal do desfecho. Resultados: Foram estudados 45 pacientes classificados como portadores de TBL por apresentarem teste tuberculÃnico (TT) &#8805; 5 mm e radiografia de tÃrax normal ou com lesÃes residuais mÃnimas. A maioria era do sexo feminino (56%), cerca da metade estava na faixa etÃria de 40 a 49 anos (45%). Em relaÃÃo à doenÃa de base tivemos diagnÃsticos reumatolÃgicos â artrite reumatÃide e espondilite (49,0%), dermatolÃgicos â psorÃase (37,7%) e doenÃa de Chron (13,3%). A presenÃa de 01 comorbidades foi observada em15/45 (33,3%) e em 6/45 (13,3%) pacientes apresentavam mais de uma doenÃa associada. Contato com paciente de TB foi relatado em 9/45 (20%) dos indivÃduos estudados. Dois pacientes referiram TB pulmonar tratada anteriormente. A maioria (88,9%) era de assintomÃticos respiratÃrios. O resultado mÃdio do TT foi 14,6mm, variando de 5 a 30 mm, sendo que 30/45 (66,7%) apresentou TT >10 mm. O uso de medicaÃÃo antiinflamatÃria nÃo influiu no resultado do TT. A anÃlise radiolÃgica do tÃrax foi normal em 64,4% e em 35,6 % foram observadas alteraÃÃes radiolÃgicas mÃnimas. Dos 45 pacientes estudados 37 utilizaram fÃrmacos para tratamento da doenÃa de base, 20 (54,0%) usaram corticosterÃides (prednisona) e 36 (97,3%) relataram o uso de imunossupressores, principalmente o Metrotexato. A isoniazida 300mg/dia foi utilizada no tratamento da TBL e os efeitos colaterais ocorreram em 15,6 % dos pacientes. Em relaÃÃo ao desfecho foi observado que 41 completaram o tratamento. Houve 01 abandono, 01 transferÃncia e 02 suspensÃes de tratamento por hepatite medicamentosa. ConclusÃo: A determinaÃÃo do perfil do paciente candidato ao tratamento da TBL pode contribuir para a uniformizaÃÃo dos procedimentos de rastreio e prevenÃÃo da TB, bem como para estabelecer os protocolos clÃnicos de uso e acompanhamento dos fÃrmacos anti-TNF. Todos os pacientes continuam em acompanhamento no ambulatÃrio de tisiologia do HUWC/UFC por um perÃodo mÃnimo de 5 anos

Glucocorticoids induce the production of the chemoattractant CCL20 in airway epithelium

Th17-mediated neutrophilic airway inflammation has been implicated in decreased response to glucocorticoids in asthma. We aimed to investigate the effect of glucocorticoids on the airway epithelial release of the neutrophilic and Th17-cell chemoattractant CCL20. We studied CCL20 and CXCL8 sputum levels in asthmatic subjects using inhaled glucocorticoids or not, and the effect of budesonide on CCL20 and CXCL8 production in primary bronchial epithelial cells. The mechanism behind the effect of budesonide-induced CCL20 production was studied in 16HBE14o- cells using inhibitors for the glucocorticoid receptor, intracellular pathways and metalloproteases. We observed higher levels of CCL20, but not CXCL8, in the sputum of asthmatics who used inhaled glucocorticoids. CCL20 levels correlated with inhaled glucocorticoid dose and sputum neutrophils. Budesonide increased tumour necrosis factor (TNE)-alpha-induced CCL20 by primary bronchial epithelium, while CXCL8 was suppressed. In 16HBE14o- cells, similar effects were observed at the CCL20 protein and mRNA levels, indicating transcriptional regulation. Although TNF-alpha-induced CCL20 release was dependent on the ERK, p38 and STAT3 pathways, the increase by budesonide was not. Inhibition of glucocorticoid receptor or ADAM17 abrogated the budesonide-induced increase in CCL20 levels. We show that glucocorticoids enhance CCL20 production by bronchial epithelium, which may constitute a novel mechanism in Th17-mediated glucocorticoid-insensitive inflammation in asthma

On the complexities of utilizing large-scale lightpath-connected distributed cyberinfrastructure

In Autumn 2013, we—an international team of climate scientists, computer scientists, eScience researchers, and e-Infrastructure specialists—participated in the enlighten your research global competition, organized to showcase advanced lightpath technologies in support of state-of-the-art research questions. As one of the winning entries, our enlighten your research global team embarked on a very ambitious project to run an extremely high resolution climate model on a collection of supercomputers distributed over two continents and connected using an advanced 10 G lightpath networking infrastructure. Although good progress was made, we were not able to perform all desired experiments due to a varying combination of technical problems, configuration issues, policy limitations and lack of (budget for) human resources to solve these issues. In this paper, we describe our goals, the technical and non-technical barriers, we encountered and provide recommendations on how these barriers can be removed so future project of this kind may succeed.</p