Fms-like tyrosine kinase 3 ligand administration overcomes a genetically determined dendritic cell deficiency in NOD mice and protects against diabetes development

A dendritic cell (DC) imbalance with a marked deficiency in CD4(-)8(+) DC occurs in non-obese diabetic (NOD) mice, a model of human autoimmune diabetes mellitus. Using a NOD congenic mouse strain, we find that this CD4(-)8(+) DC deficiency is associated with a gene segment on chromosome 4, which also encompasses non-MHC diabetes susceptibility loci. Treatment of NOD mice with fms-like tyrosine kinase 3 ligand (FL) enhances the level of CD4(-)8(+) DC, temporarily reversing the DC subtype imbalance. At the same time, fms-like tryosine kinase 3 ligand treatment blocks early stages of the diabetogenic process and with appropriately timed administration can completely prevent diabetes development. This points to a possible clinical use of FL to prevent autoimmune disease.

A highly conserved c-fms gene intronic element controls macrophage-specific and regulated expression

The c fins gene encodes the receptor for macrophage colony-stimulating factor-1. This gene is expressed selectively in the macrophage cell lineage. Previous studies have implicated sequences in intron 2 that control transcript elongation in tissue-specific and regulated expression of c -fms. Four macrophage-specific deoxyribonuclease I (DNase I)-hypersensitive sites (DHSS) were identified within mouse intron 2. Sequences of these DHSS were found to be highly conserved compared with those in the human gene. A 250-bp region we refer to as the fins intronic regulatory element (FIRE), which is even more highly conserved than the c-fins proximal promoter, contains many consensus binding sites for macrophage-expressed transcription factors including Spl, PU.1, and C/EBP. FIRE was found to act as a macrophage-specific enhancer and as a promoter with an antisense orientation preference in transient transfections. In stable transfections of the macrophage line RAW264, as well as in clones selected for high and low-level c -fms mRNA expression, the presence of intron 2 increased the frequency and level of expression of reporter genes compared with those attained using the promoter alone. Removal of FIRE abolished reporter gene expression, revealing a suppressive activity in the remaining intronic sequences. Hence, FIRE is shown to be a key regulatory element in the fins gene.

Teste de envelhecimento acelerado em sementes de crambe (Crambe abyssinica Hochst), cultivar FMS Brilhante

A utilização de sementes de alta qualidade fisiológica merece destaque na instalação de qualquer cultura, sendo necessário avaliá-las por meio dos testes de germinação e de vigor. O objetivo deste trabalho foi avaliar a eficiência do teste de envelhecimento acelerado na determinação do vigor de sementes de crambe. Foram utilizados cinco lotes de sementes de crambe, cultivar FMS Brilhante, e a qualidade inicial de cada lote foi avaliada pela determinação do teor de água, germinação, primeira contagem de germinação, emergência de plântulas e índice de velocidade de emergência. Para o teste de envelhecimento acelerado, as sementes foram submetidas a temperaturas de 41 e 43 ºC, em câmara tipo BOD, durante 48, 72 e 96 horas. No final de cada período de envelhecimento, as sementes foram colocadas para germinar, conforme método descrito para o teste de germinação. O delineamento experimental foi inteiramente casualizado, com quatro repetições por lote. O teste de envelhecimento acelerado na condição de 41 ºC, por 72 h, proporciona maior diferenciação do vigor entre os lotes de sementes de crambe, cultivar FMS Brilhante.

The Effect of Operational Disturbances on Reliability and Operation Time Distribution of NCmachine Tools in FMS

This thesis concentrates on studying the operational disturbance behavior of machine tools integrated into FMS. Operational disturbances are short term failures of machine tools which are especially disruptive to unattended or unmanned operation of FMS. The main objective was to examine the effect of operational disturbances on reliability and operation time distribution for machine tools. The theoretical part of the thesis covers the fimdamentals of FMS relating to the subject of this study. The concept of FMS, its benefits and operator's role in FMS operation are reviewed. The importance of reliability is presented. The terms describing the operation time of machine tools are formed by adopting standards and references. The concept of failure and indicators describing reliability and operational performance for machine tools in FMSs are presented. The empirical part of the thesis describes the research methodology which is a combination of automated (ADC) and manual data collection. By using this methodology it is possible to have a complete view of the operation time distribution for studied machine tools. Data collection was carried out in four FMSs consisting of a total of 17 machine tools. Each FMS's basic features and the signals of ADC are described. The indicators describing the reliability and operation time distribution of machine tools were calculated according to collected data. The results showed that operational disturbances have a significant influence on machine tool reliability and operational performance. On average, an operational disturbance occurs every 8,6 hours of operation time and has a down time of 0,53 hours. Operational disturbances cause a 9,4% loss in operation time which is twice the amount of losses caused by technical failures (4,3%). Operational disturbances have a decreasing influence on the utilization rate. A poor operational disturbance behavior decreases the utilization rate. It was found that the features of a part family to be machined and the method technology related to it are defining the operational disturbance behavior of the machine tool. Main causes for operational disturbances were related to material quality variations, tool maintenance, NC program errors, ATC and machine tool control. Operator's role was emphasized. It was found that failure recording activity of the operators correlates with the utilization rate. The more precisely the operators record the failure, the higher is the utilization rate. Also the FMS organizations which record failures more precisely have fewer operational disturbances.

A pesquisa como dispositivo para o exercício no PET-Saúde UFF/FMS Niterói

O PET-Saúde (Programa de Educação pelo Trabalho para a Saúde) proposto pela Universidade Federal Fluminense (UFF) e pela Fundação Municipal de Saúde de Niterói (FMS) iniciou suas atividades em abril de 2010 com a proposta de desenvolver o processo de ensino-aprendizagem de forma participativa, tendo como eixo central o trabalho no cotidiano dos serviços de saúde, utilizando as ferramentas da pesquisa e avaliação em saúde como elemento disparador do aprendizado. As atividades são desenvolvidas na perspectiva da construção de um diagnóstico de saúde da área de abrangência de cada unidade de saúde à qual o grupo PET está vinculado. A metodologia adotada pelos grupos consiste na investigação participativa, com o envolvimento de profissionais, alunos, usuários e docentes. Como ferramenta vem sendo utilizada a construção da história local, com levantamento de documentos e depoimentos da comunidade. Destaca-se a atividade de cadastramento e recadastramento de famílias e o levantamento do perfil epidemiológico dos territórios. Neste primeiro estágio, identificamos a interação em grupo multiprofissional como um desafio que vem proporcionando grandes avanços no entendimento do processo saúde-doença entre estudantes, docentes e profissionais.

Hermanos Maristas de la Enseñanza -FMS-.

La orden de los Maristas es fundada en el siglo XVIII en Francia por Marcelino Champagnat. Inicia su labor educativa en pequeños municipios y aldeas y ahora está presente en setenta y seis países del mundo. Las primeras comunidades trabajan con el precepto de formar buenos cristianos y buenos ciudadanos. El modelo de educación marista se ha ido adaptando con los tiempos y está en renovación constante. Están dedicados a la educación de los jóvenes, en especial de los más desfavorecidos. Adjunta una ficha con los datos y direcciones de la congregación.

First-trimester serum levels of soluble endoglin and soluble fms-like tyrosine kinase-1 as first-trimester markers for late-onset preeclampsia

OBJECTIVE: The aim of this investigation was to assess soluble endoglin (sEng) and soluble fms-like tyrosine kinase-1 (sFlt1) as first-trimester serum markers to predict preeclampsia. STUDY DESIGN: First-trimester sera were obtained from 46 women with subsequent late-onset preeclampsia and from 92 controls. sEng and sFlt1 concentrations were determined immunoanalytically. Correlation analysis with inhibin A and placental growth factor levels was performed. RESULTS: sEng and sFlt1 serum concentrations were higher in women with subsequent preeclampsia than in controls (mean +/- SD, sEng: 5.57 +/- 1.18 ng/mL vs 5.02 +/- 1.01 ng/mL, P = .009; sFlt1: 1764 +/- 757 pg/mL vs 1537 +/- 812 pg/mL, P = .036). Sensitivities and specificities for predicting preeclampsia were 63% and 57% for sEng and 64% and 56% for sFlt1, respectively. When sEng and inhibin A were combined, the sensitivity increased to 68%, whereas the specificity was 61%. CONCLUSION: sEng and sFlt1 are increased in the first trimester in women with subsequent late-onset preeclampsia and might therefore prove useful to predict preeclampsia.

Pluripotent hematopoietic stem cells contain high levels of mRNA for c-kit, GATA-2, p45 NF-E2, and c-myb and low levels or no mRNA for c-fms and the receptors for granulocyte colony-stimulating factor and interleukins 5 and 7.

Pluripotent hematopoietic stem cells (PHSCs) were highly enriched from mouse bone marrow by counterflow centrifugal elutriation, lineage subtraction, and fluorescence-activated cell sorting based on high c-kit receptor expression (c-kitBR). We used reverse transcriptase polymerase chain reaction to assay the c-kitBR subset and the subsets expressing low (c-kitDULL) and no (c-kitNEG) c-kit receptor for expression of mRNA encoding hematopoietic growth factor receptors and transcription factors. The c-kitBR cells had approximately 3.5-fold more c-kit mRNA than unfractionated bone marrow cells. The c-kitDULL cells had 47-58% of the c-kit mRNA found in c-kitBR cells and the c-kitNEG cells had 4-9% of the c-kit mRNA present in c-kitBR cells. By comparing mRNA levels in c-kitBR cells (enriched for PHSCs) with those of unfractionated bone marrow, we demonstrated that c-kitBR cells contained low or undetectable levels of mRNA for c-fms, granulocyte colony-stimulating factor receptor, interleukin 5 receptor (IL-5R), and IL-7R. These same cells had moderate levels of mRNA for erythropoietin receptor, IL-3R subunits IL-3R alpha (SUT-1), AIC-2A, and AIC-2B, IL-6R and its partner gp-130, and the transcription factor GATA-1 and high levels of mRNA for transcription factors GATA-2, p45 NF-E2, and c-myb. We conclude from these findings that PHSCs are programmed to interact with stem cell factor, IL-3, and IL-6 but not with granulocyte or macrophage colony-stimulating factor. These findings also indicate that GATA-2, p45 NF-E2, and c-myb activities may be involved in PHSC maintenance or proliferation.

Expression of the fms-like tyrosine kinase 4 gene becomes restricted to lymphatic endothelium during development.

We have recently cloned the human fms-like tyrosine kinase 4 gene FLT4, whose protein product is related to two vascular endothelial growth factor receptors FLT1 and KDR/FLK1. Here the expression of FLT4 has been analyzed by in situ hybridization during mouse embryogenesis and in adult human tissues. The FLT4 mRNA signals first became detectable in the angioblasts of head mesenchyme, the cardinal vein, and extraembryonally in the allantois of 8.5-day postcoitus (p.c.) embryos. In 12.5-day p.c. embryos, the FLT4 signal decorated developing venous and presumptive lymphatic endothelia, but arterial endothelia were negative. During later stages of development, FLT4 mRNA became restricted to vascular plexuses devoid of red cells, representing developing lymphatic vessels. Only the lymphatic endothelia and some high endothelial venules expressed FLT4 mRNA in adult human tissues. Increased expression occurred in lymphatic sinuses in metastatic lymph nodes and in lymphangioma. Our results suggest that FLT4 is a marker for lymphatic vessels and some high endothelial venules in human adult tissues. They also support the theory on the venous origin of lymphatic vessels.