Colony-stimulating factor-1 suppresses responses to CpG DNA and expression of toll-like receptor 9 but enhances responses to lipopolysaccharide in murine macrophages

During bacterial infections, the balance between resolution of infection and development of sepsis is dependent upon the macrophage response to bacterial products. We show that priming of murine bone marrow-derived macrophages (BMMs) with CSF-1 differentially regulates the response to two such stimuli, LPS and immunostimulatory (CpG) DNA. CSF-1 pretreatment enhanced IL-6, IL-12, and TNF-alpha production in response to LPS but suppressed the same response to CpG DNA. CSF-1 also regulated cytokine gene expression in response to CpG DNA and LPS; CpG DNA-induced IL-12 p40, IL-12 p35, and TNF-alpha mRNAs were all suppressed by CSF-1 pretreatment. CSF-1 pretreatment enhanced LPS-induced IL-12 p40 mRNA but not TNF-alpha and IL-12 p35 mRNAs, suggesting that part of the priming effect is posttranscriptional. CSF-1 pretreatment also suppressed CpG DNA-induced nuclear translocation of NF-kappaB and phosphorylation of the mitogen-activated protein kinases p38 and extracellular signal-related kinases-1/2 in BMMs, indicating that early events in CpG DNA signaling were regulated by CSF-1. Expression of Toll-like receptor (TLR)9, which is necessary for responses to CpG DNA, was markedly suppressed by CSF-1 in both BMMs and thioglycolate-elicited peritoneal macrophages. CSF-1 also down-regulated expression of TLR1, TLR2, and TLR6, but not the LPS receptor, TLR4, or TLR5. Hence, CSF-1 may regulate host responses to pathogens through modulation of TLR expression. Furthermore, these results suggest that CSF-1 and CSF-1R antagonists may enhance the efficacy of CpG DNA in vivo.

Matrix metalloproteinase-2 and-9 involvement in canine tumors

Matrix metalloproteinases (MMPs) are a family of enzymes implicated in the degradation and remodeling of extracellular matrix and in vascularization. They are also involved in pathologic processes such as tumor invasion and metastasis in experimental cancer models and in human malignancies. We used gelatin zymography and inummohistochemistry to determine whether MMP-2 and MMP-9 are present in canine tumors and normal tissues and whether MMP production correlates with clinicopathologic parameters of prognostic importance. High levels of pro-MMP-9, pro-MMP-2, and active MMP-2 were detected in most canine tumors. Significantly higher MMP levels were measured in canine tumors than in nontumors, malignancies had higher MMP levels than benign tumors, and sarcomas had higher active MMP-2 than carcinomas. Cartilaginous tumors produced higher MMP levels than did nonsarcomatous malignancies, benign tumors, and normal tissues, and significantly greater MMP-2 than osteosarcomas and fibrosarcomas. Pro-MMP-9 production correlated with the histologic grade of osteosarcomas. The 62-kd form of active MMP-2 was detected only in high-grade, p53-positive, metastatic malignancies. Zymography proved to be a sensitive and quantitative technique for the assessment of MMP presence but has the limitation of requiring fresh tissue; inummohistochemistry is qualitative and comparatively insensitive but could be of value in archival studies. MMP presence was shown in a range of canine tumors, and their link to tumor type and grade was demonstrated for the first time. This study will allow a substantially improved evaluation of veterinary cancer patients and provides baseline information necessary for the design of clinical trials targeting MMPs.

Large sets of large sets of Steiner triple systems of order 9

We describe a direct method of partitioning the 840 Steiner triple systems of order 9 into 120 large sets. The method produces partitions in which all of the large sets are isomorphic and we apply the method to each of the two non-isomorphic large sets of STS(9).

Decreased coumarin 7-hydroxylase activities and CYP2A6 expression levels in humans caused by genetic polymorphism in CYP2A6 promoter region (CYP2A6*9)

One of seven poor metabolizers of coumarin found in Thai subjects was previously genotyped as heterozygote for the CYP2A6*4 (whole deletion) and CYP2A6*9. Thus, we aimed to investigate the relationship between the genetic polymorphism in the TATA box of the CYP2A6 gene (CYP2A6*9), expression levels of CYP2A6 mRNA and coumarin 7-hydroxylase activities in human livers. Levels of CYP2A6 mRNA were quantified by real-time quantitative reverse transcriptase-polymerase chain reaction. The mean expression levels of CYP2A6 mRNA in individuals with CYP2A6*1/*4, CYP2A6*1/*9 and CYP2A6*4/*9 were 58%, 71% and 21% of the individuals genotyped as CYP2A6*1/*1, respectively. The mean in-vitro coumarin 7-hydroxylase activities in subjects carrying CYP2A6*1/*4, CYP2A6*1/*9 and CYP2A6*4/*9 were 41%, 71% and 12%, respectively, compared to those of the subjects judged as wild-type. Vmax values for coumarin 7-hydroxylation in the liver microsomes from human subjects with genotypes of CYP2A6*1/*1, CYP2A6*1/*4, CYP2A6*1/*9 and CYP2A6*4/*9 were 0.58, 0.26, 0.44 and 0.13 nmol/min/nmol total P450, respectively. CYP2A6 protein levels in human liver microsomes with the CYP2A6*4 and the CYP2A6*9 alleles were markedly decreased. These results suggest that the genetic polymorphism in the promoter region of the CYP2A6 gene (CYP2A6*9) reduced the expression levels of CYP2A6 mRNA and protein in human livers, resulting in the decrease of coumarin 7-hydroxylase activities. Individuals judged as CYP2A6*4/*9 were expected to be poor metabolizers, having extremely low activity of CYP2A6.

The synthesis and X-ray crystal structure of 9-carboxyhexahydro-7-methoxy-4a,7-ethano-benzopyran-5-en-1-one

9-Carboxyhexahydro-7-methoxy-4a,7-ethano-benzopyran-5-en-1-one (1) was prepared and examined by X-ray crystallography to probe its potential as a new peptide scaffold/template. The crystal structure of the anhydride precursor 7-(2-acetoxyethyl)-4-methoxy-3a,4,7,7a-tetrahydro-4,7-ethanoisobenzofuran-1,3-dione (6) is also reported.

A????es premiadas no 9?? Concurso Inova????o na Gest??o P??blica Federal 2004

Nesta publica????o, referente ao 9?? Concurso Inova????o na Gest??o P??blica Federal, o leitor encontrar?? iniciativas inovadoras nas seguintes ??reas: Articula????o de parcerias; atendimento ao cidad??o e inclus??o digital; gerenciamento de custos; planejamento e gest??o estrat??gica; simplifica????o e agiliza????o de procedimentos

Texto para discuss??o 9: administra????o p??blica gerencial: estrat??gia e estrutura para um novo Estado

Na d??cada de 80, logo depois da eclos??o da crise de endividamento internacional, o tema que prendeu a aten????o de pol??ticos e economistas em todo o mundo foi o ajuste estrutural ou, em termos mais anal??ticos, o ajuste fiscal e as reformas orientadas para o mercado. Nos anos 90, embora o ajuste estrutural permane??a entre os principais objetivos, a ??nfase deslocou-se para a reforma do Estado, particularmente para a reforma administrativa. A quest??o central hoje ?? como reconstruir o Estado ??? como redefinir o novo Estado que est?? surgindo em um mundo globalizado

M??dulo 9 - comiss??o de licita????o: curso legisla????o aplicada ?? log??stica de suprimentos Lei 8.666/93, preg??o e registro de pre??os

Este documento trata de: aspectos conceituais da lei: finalidade, import??ncia e hierarquia da lei.; no????es gerais da lei de licita????es - Lei n?? 8.666/93; tipos de licita????o:menor pre??o, melhor t??cnica, t??cnica e pre??o e maior lance ou oferta; modalidades de licita????o: concorr??ncia, tomada de pre??os, convite, concurso e leil??o; exce????es ?? obrigatoriedade de licita????o: dispensa e inexigibilidade; regime de execu????o indireta; comiss??o de licita????o; etapas do processo licitat??rio: edital, procedimentos/documentos do certame, registro cadastral, habilita????o dos interessados, julgamento e encerramento; preg??o; registro de pre??os

Curso de especializa????o em gest??o p??blica: 9?? edi????o - 2013/2014

A especializa????o em Gest??o P??blica ?? um curso de p??s-gradua????o "lato sensu" oferecido pela ENAP desde 2002. ?? um curso que busca contribuir para a melhoria da gest??o p??blica, promovendo a forma????o profissional dos servidores p??blicos do Poder Executivo Federal. O curso foi concebido de forma a aproximar os participantes das quest??es concretas da pr??tica governamental, com estrat??gias de ensino te??rico-aplicado, por meio de instrumentos did??tico-pedag??gicos que facilitem a apropria????o daquela realidade, sua an??lise e enfrentamento dos problemas identificados

Disciplina 4.9: sistema de or??amento federal

O Sistema de Or??amento Federal: ??rg??o central (SOF), ??rg??os setoriais e seccionais; processo e sistema or??ament??rio. As fun????es do or??amento. Aspectos institucionais e legais da fun????o or??ament??ria. Contexto legal e normativo do processo or??ament??rio. Modelos or??ament??rios. A reforma gerencial do or??amento (nova concep????o de programa). Classifica????es or??ament??rias e a transpar??ncia das opera????es or??ament??rias. Classifica????o funcional e estrutura program??tica, tipos de opera????es or??ament??rias (atividades, projetos e opera????es especiais). Classifica????o da despesa. A Lei de Responsabilidade Fiscal: princ??pios de responsabilidade na gest??o das finan??as p??blicas nacionais; a LRF como mecanismo de controle das contas p??blicas; as inova????es or??ament??rias; novas atribui????es da Lei de Diretrizes Or??ament??rias; a Receita P??blica ap??s a LRF; as Novas Exig??ncias para a Gera????o de Despesas P??blicas; a D??vida P??blica; a transpar??ncia na elabora????o e execu????o dos instrumentos de planejamento, execu????o e presta????o de contas; a responsabilidade civil, penal e administrativa dos gestores p??blicos.

9?? Encontro Nacional de Escolas de Governo

Este relat??rio apresenta uma s??ntese dos resultados do IX Encontro Nacional de Escolas de Governo, realizado na Escola Nacional de Administra????o P??blica, ENAP, nos dias 24 e 25 de maio de 2012, Em Bras??lia.

9?? concurso inova????o na gest??o p??blica federal: id??ias que fazem diferen??a

Para premiar e incentivar a gera????o e incorpora????o de novas pr??ticas e conhecimentos na gest??o p??blica, a ENAP e o Minist??rio do Planejamento, Or??amento e Gest??o promovem, desde 1996, o Concurso Inova????o na Gest??o P??blica Federal. Em 2004, os tr??s primeiros colocados foram o Sistema Radar Comercial, do Minist??rio do Desenvolvimento, Ind??stria e Com??rcio Exterior (MDIC), o Sistema de Custos e Informa????es Gerenciais, do Banco Central (Bacen), e o Centro de Pesquisas do HCPA: Inovando a gest??o da pesquisa, por meio de laborat??rios compartilhados, do Hospital de Cl??nicas de Porto Alegre (HCPA). A RSP conversou com as equipes vencedoras do 9?? Concurso Inova????o na Gest??o P??blica Federal para relatar um pouco de suas experi??ncias.