Germline mutations in TMEM127 confer susceptibility to pheochromocytoma

Pheochromocytomas, which are catecholamine-secreting tumors of neural crest origin, are frequently hereditary(1). However, the molecular basis of the majority of these tumors is unknown(2). We identified the transmembrane-encoding gene TMEM127 on chromosome 2q11 as a new pheochromocytoma susceptibility gene. In a cohort of 103 samples, we detected truncating germline TMEM127 mutations in approximately 30% of familial tumors and about 3% of sporadic-appearing pheochromocytomas without a known genetic cause. The wild-type allele was consistently deleted in tumor DNA, suggesting a classic mechanism of tumor suppressor gene inactivation. Pheochromocytomas with mutations in TMEM127 are transcriptionally related to tumors bearing NF1 mutations and, similarly, show hyperphosphorylation of mammalian target of rapamycin (mTOR) effector proteins. Accordingly, in vitro gain-of-function and loss-of-function analyses indicate that TMEM127 is a negative regulator of mTOR. TMEM127 dynamically associates with the endomembrane system and colocalizes with perinuclear (activated) mTOR, suggesting a subcompartmental-specific effect. Our studies identify TMEM127 as a tumor suppressor gene and validate the power of hereditary tumors to elucidate cancer pathogenesis.

Mycobacterium tuberculosis Culture Filtrate Proteins plus CpG Oligodeoxynucleotides Confer Protection to Mycobacterium bovis BCG-Primed Mice by Inhibiting Interleukin-4 Secretion

Culture filtrate proteins (CFP) are potential targets for tuberculosis vaccine development. We previously showed that despite the high level of gamma interferon (IFN-gamma) production elicited by homologous immunization with CFP plus CpG oligodeoxynucleotides (CFP/CpG), we did not observe protection when these mice were challenged with Mycobacterium tuberculosis. In order to use the IFN-gamma-inducing ability of CFP antigens, in this study we evaluated a prime-boost heterologous immunization based on CFP/CpG to boost Mycobacterium bovis BCG vaccination in order to find an immunization schedule that could induce protection. Heterologous BCG-CFP/CpG immunization provided significant protection against experimental tuberculosis, and this protection was sustained during the late phase of infection and was even better than that conferred by a single BCG immunization. The protection was associated with high levels of antigen-specific IFN-gamma and interleukin-17 (IL-17) and low IL-4 production. The deleterious role of IL-4 was confirmed when IL-4 knockout mice vaccinated with CFP/CpG showed consistent protection similar to that elicited by BCG-CFP/CpG heterologous immunization. These findings show that a single dose of CFP/CpG can represent a new strategy to boost the protection conferred by BCG vaccination. Moreover, different immunological parameters, such as IFN-gamma and IL-17 and tightly regulated IL-4 secretion, seem to contribute to the efficacy of this tuberculosis vaccine.

TNF microsatellite alleles may confer protection against the development of lipodystrophy syndrome in Brazilian HIV patients

P>The aim of this study was to evaluate the frequency of TNFa-e microsatellites and the promoter region (TNF-308 and TNF-238) in HIV/AIDS-infected patients presenting or not lipodystrophy syndrome (LS). The design is the genetic case-control association study. Microsatellite and the TNF promoter region polymorphisms were amplified by PCR and submitted to polyacrylamide gel electrophoresis. The genotypes and allele frequencies for 67 HIV-positive patients with lipodystrophy were compared with 50 HIV-positive patients with no evidence of lipodystrophy and with 131 healthy HIV-negative individuals. The presence of the TNFa5 allele could provide HIV/AIDS patients with protection against developing LS. The presence of TNF-308G allele, as well as of its homozygote TNF-308GG, were associated with susceptibility to developing LS. In addition, the presence of the haplotype TNFe3-d3-238G-308A-c1-a5-b7 suggests protection against developing that syndrome. This study highlights that polymorphic sites spanning the region nearby the TNF locus are associated with LS development in HIV/AIDS patients.

Genetic linkage analysis of the lesser grain borer Rhyzopertha dominica identifies two loci that confer high-level resistance to the fumigant phosphine

High levels of inheritable resistance to phosphine in Rhyzopertha dominica have recently, been detected in Australia and hi art effort to isolate the genes responsible For resistance we have used random amplified DNA fingerprinting (RAF) to produce a genetic linkage map of R. dominica. The map consists of 94 dominant DNA markers with art average distance between markers of 4.6 cM and defines nine linkage groups with a total recombination distance of 390.1 cM. We have identified two loci that are responsible for high-level resistance. One provides similar to50x resistance to phosphine while the other provides 12.5x resistance and in combination, the two genes act synergistically to provide a resistance level 250 x greater than that of fully susceptible beetles. The haploid genome size has been determined to be 4.76 x 10(8) bp, resulting in an average physical distance of 1.2 Mbp per map unit. No recombination has been observed between either of the two resistance loci and their adjacent DNA markers in a population of 44 fully resistant F-5 individuals, which indicates that the genes are likely to reside within 0.91 cM (1.1 Mbp) of the DNA markers.

Confer??ncias nacionais de sa??de e processos participativos na administra????o p??blica federal brasileira

Este caso aborda as Confer??ncias Nacionais de Sa??de (CNS) enquanto espa??os institucionais leg??timos de participa????o social que contribuem para a emerg??ncia de uma governan??a apoiada em cidadania mais engajada e ativa. O estudo de caso pretende fomentar o debate sobre a emerg??ncia de novos padr??es de rela????o entre o Estado e sociedade, e sobre o avan??o da resili??ncia nas organiza????es sociais e nas institui????es p??blicas. Pretende tamb??m levantar os novos desafios colocados para os gestores p??blicos com a amplia????o da participa????o e diversidade dos atores, al??m de maior especificidade das demandas, o que gera maiores dificuldades na obten????o de consensos e na elei????o de prioridades. O caso pode ser aplicado em cursos que abordem tem??ticas relacionadas ?? participa????o social, redes sociais, governan??a, democracia e pol??ticas p??blicas

O lugar do género, dos homens e das mulheres na sociologia portuguesa: uma análise a partir da Associação Portuguesa de Sociologia e seus congressos

O e-working paper que se apresenta insere-se no campo analítico da sociologia da ciência, e tem como objectivos, por um lado, compreender como o género se constitui, ou não, como um elemento estruturante na distribuição dos actores pelo campo disciplinar e, por outro lado, explorar as configurações que a sociologia do género tem assumido na produção científica nacional. Os Congressos Portugueses de Sociologia (1988 a 2008), e a Associação Portuguesa de Sociologia constituíram o material empírico que possibilitou o exercício. This e-working paper integrates the realm of sociology of science, and aimed, on one hand, to understand how gender is a structural element in the distribution of actors within the disciplinary field and, on the other hand, to explore the configurations of sociology of gender in the scientific production. Therefore, the analysis is produced from two privileged empirical objects: the Portuguese Congress of Sociology (1988 to 2008) and the Portuguese Association of Sociology.

Fiscalização da empreitada do "Centro de Congressos, Feiras e Exposições de Oeiras": estrutura metálica da cobertura

O presente relatório é referente ao trabalho realizado na empresa Prospectiva, S.A. , e procurou descrever os trabalhos realizados para a execução da estrutura metálica da cobertura do Centro de Congressos de Oeiras. Foi feita uma pequena apresentação da empresa assim como uma descrição global mas pouco detalhada da obra em causa. Foram descritas as principais fases da execução de estruturas metálicas como, o fabrico e a montagem dos elementos, assim como o seu enquadramento com as principais disposições regulamentares impostas a este tipo de estrutura. Na fase de fabrico foram descritos todos os processos envolvidos desde a recepção da matéria-prima até ao produto final das peças, fazendo sempre um acompanhamento com o Plano de Inspecção e Ensaio da fase de fabrico. No caso da montagem da estrutura foi feita a descrição do processo de transporte e o acompanhamento das principais fases da montagem, como o seu planeamento e faseamento, até a sua importância no próprio planeamento global da obra. Foram também apresentados os equipamentos utilizados, estruturas de apoio à montagem e os tipos de ligações executadas.

Immunoglobulin Fc receptors in clinical strains of Staphylococcus aureus do not confer resistance to Phagocytosis in an in vitro assay

Staphylococcus aureus binds Immunoglobulin G (IgG) on its external surface due to the presence of specific receptors for the Fc domain of this immunoglobulin. This mechanism represents a kind of camouflage against phagocytic cells. In order to confirm that possibility an in vitro evaluation of the phagocytic activity of leukocytes polymorpho-nuclear (PMN) against strains of Staphylococcus aureus was done, comparing 18 strains isolated from clinical samples and 16 from healthy individuals. The presence of Fc receptors was evaluated by haemagglutination (HA) with erythrocytes group A after incubation of the strains with IgG anti blood group A. Phagocytosis of S. aureus was carried out by mixing live bacteria with a suspension of human PMN and incubating at 37 °C for 1 h; survivors were counted as colony forming units by plating. The strains from clinical specimens showed higher HA than those from healthy individuals (p = 0.01); but the former were killed more efficiently than the latter (80-90% and 40%, respectively). It is may be possible that S. aureus showed different behavior in vivo, where could express other virulence factors to prevent the action of phagocytes.

CD4+, CD8+ and CD4- CD8- T cell-subsets can confer protection against Leishmania m. mexicana infection

We studied the role of CD4+, CD8+, CD4- CD8- T cells and IgG anti-Leishmania after infection or vaccination in the CBA/ca mouse. Mice were either infected with L. m. mexicana promastigotes or vaccinated with parasite-membrane antigens incorporated into liposomes. Successfully vaccinated mice were used as cell-donors in adoptive transfer experiments. Naive, syngeneic recipients received highly-enriched CD4+, CD8+ or CD4- CD8- T cells from those two set of donors and challenged with live parasites. Our results showed that, both CD4+ and CD8+ T cells from infected or vaccinated donors conferred significant disease-resistance to naive recipients. In addition, adoptive transfer of CD4- CD8- T cells from vaccinated donors significantly delayed lesion growth in recipient mice. We concluded that vaccination of CBA mice correlates with the induction of protective CD4+, CD8+ and CD4- CD8- T cells and the synthesis of IgG anti-Leishmania.

Natural Arabidopsis brx loss-of-function alleles confer root adaptation to acidic soil.

Soil acidification is a major agricultural problem that negatively affects crop yield. Root systems counteract detrimental passive proton influx from acidic soil through increased proton pumping into the apoplast, which is presumably also required for cell elongation and stimulated by auxin. Here, we found an unexpected impact of extracellular pH on auxin activity and cell proliferation rate in the root meristem of two Arabidopsis mutants with impaired auxin perception, axr3 and brx. Surprisingly, neutral to slightly alkaline media rescued their severely reduced root (meristem) growth by stimulating auxin signaling, independent of auxin uptake. The finding that proton pumps are hyperactive in brx roots could explain this phenomenon and is consistent with more robust growth and increased fitness of brx mutants on overly acidic media or soil. Interestingly, the original brx allele was isolated from a natural stock center accession collected from acidic soil. Our discovery of a novel brx allele in accessions recently collected from another acidic sampling site demonstrates the existence of independently maintained brx loss-of-function alleles in nature and supports the notion that they are advantageous in acidic soil pH conditions, a finding that might be exploited for crop breeding.

16p11.2 600 kb Duplications confer risk for typical and atypical Rolandic epilepsy.

Rolandic epilepsy (RE) is the most common idiopathic focal childhood epilepsy. Its molecular basis is largely unknown and a complex genetic etiology is assumed in the majority of affected individuals. The present study tested whether six large recurrent copy number variants at 1q21, 15q11.2, 15q13.3, 16p11.2, 16p13.11 and 22q11.2 previously associated with neurodevelopmental disorders also increase risk of RE. Our association analyses revealed a significant excess of the 600 kb genomic duplication at the 16p11.2 locus (chr16: 29.5-30.1 Mb) in 393 unrelated patients with typical (n = 339) and atypical (ARE; n = 54) RE compared with the prevalence in 65,046 European population controls (5/393 cases versus 32/65,046 controls; Fisher's exact test P = 2.83 × 10(-6), odds ratio = 26.2, 95% confidence interval: 7.9-68.2). In contrast, the 16p11.2 duplication was not detected in 1738 European epilepsy patients with either temporal lobe epilepsy (n = 330) and genetic generalized epilepsies (n = 1408), suggesting a selective enrichment of the 16p11.2 duplication in idiopathic focal childhood epilepsies (Fisher's exact test P = 2.1 × 10(-4)). In a subsequent screen among children carrying the 16p11.2 600 kb rearrangement we identified three patients with RE-spectrum epilepsies in 117 duplication carriers (2.6%) but none in 202 carriers of the reciprocal deletion. Our results suggest that the 16p11.2 duplication represents a significant genetic risk factor for typical and atypical RE.

Distinct sets of alphabeta TCRs confer similar recognition of tumor antigen NY-ESO-1157-165 by interacting with its central Met/Trp residues.

Naturally acquired immune responses against human cancers often include CD8(+) T cells specific for the cancer testis antigen NY-ESO-1. Here, we studied T cell receptor (TCR) primary structure and function of 605 HLA-A*0201/NY-ESO-1(157-165)-specific CD8 T cell clones derived from five melanoma patients. We show that an important proportion of tumor-reactive T cells preferentially use TCR AV3S1/BV8S2 chains, with remarkably conserved CDR3 amino acid motifs and lengths in both chains. All remaining T cell clones belong to two additional sets expressing BV1 or BV13 TCRs, associated with alpha-chains with highly diverse VJ usage, CDR3 amino acid sequence, and length. Yet, all T cell clonotypes recognize tumor antigen with similar functional avidity. Two residues, Met-160 and Trp-161, located in the middle region of the NY-ESO-1(157-165) peptide, are critical for recognition by most of the T cell clonotypes. Collectively, our data show that a large number of alphabeta TCRs, belonging to three distinct sets (AVx/BV1, AV3/BV8, AVx/BV13) bind pMHC with equal antigen sensitivity and recognize the same peptide motif. Finally, this in-depth study of recognition of a self-antigen suggests that in part similar biophysical mechanisms shape TCR repertoires toward foreign and self-antigens.

Congressos amb més articles Campus del Baix Llobregat (CBL) - 2011

Es presenta la llista de congressos en les que més han participat els autors del CBL ordenat per centres. Si el centre no apareix vol dir que els congressos en el que han participat els seus autors no están buidats a l’SCOPUS.

Nous conceptes en cosmètica. La importància de la innovació i dels congressos.

El 2010 la cosmètica va generar un volum de negoci de 5.200 milions a Espanya.