Rare autosomal dominant hereditary hemochromatosis associated with SLC40A1 gene: ferroportin disease or type 4 hereditary hemochromatosis?

Ferroportin (FPN1), encoded by the SLC40A1 gene, is the unique cellular iron exporter identified in mammals. FPN1 transfers iron from the intestine and macrophages into the bloodstream. This function is negatively regulated by hepcidin. Mutations in SLC40A1 may affect FPN1 function, originating distinct autosomal dominant diseases: (i) the Ferroportin Disease (FD), due to loss-of-function mutations, is characterized by decreased iron export from enterocytes and severely affected iron transfer in macrophages, giving rise to a marked iron accumulation in spleen and liver; and (ii) the Type 4 Hereditary Hemochromatosis (HH), resulting from gain-of-function mutations conferring resistance to hepcidin-mediated FPN1 degradation and consequently high cellular iron export. In this study, 335 individuals suspected of having non-classic HH were enrolled. Six genes related with iron metabolism were analysed by SSCP, dHPLC or NGS. The latter used TruSeq or Nextera XT libraries and a MiSeq platform (Illumina). Genetic variants found were validated by Sanger sequencing. Predictive consequences at protein level were evaluated using Polyphen-2 and SIFT softwares. From all patients analysed, three SLC40A1 pathogenic variants were detected in heterozygosity in three women: two missense, c.238G>A, p.Gly80Ser and c.610G>A, p.Gly204Ser; and one deletion, c.485_487delTTG; p.Val162del. These variants had been reported in public databases, but they were not known to be present in the Portuguese population. The p.Gly80Ser and the p.Val162del are FPN1 loss-of-function mutations and were found associated with hyperferritinemia and low transferrin saturation (FD). In contrast, the p.Gly204Ser induced a gain of FPN1 function with a full iron export capacity giving the patient a type 4-HH phenotype, which includes iron overload, hyperferritinemia and high transferrin saturation. Detailed clinical evaluation of the suspected patients are useful to unravel the effect of different mutations in FPN1 function, expression and regulation.This work was partially supported by INSA_2013DGH910 and GenomePT (POCI-01-0145-FEDER-022184).info:eu-repo/semantics/publishedVersio

Novel mutation in addition to functional TMPRSS6 gene polymorphisms originate an IRIDA-like phenotype in an African child

Iron-refractory iron deficiency anemia (IRIDA) is a rare autosomal recessive anemia often unresponsive to oral iron intake and partially responsive to parenteral iron treatment. The disease originates from mutations in TMPRSS6 gene, encoding Matriptase 2, a transmembrane serine protease that plays an essential role in down-regulating hepcidin. Once TMPRSS6 is mutated, the corresponding protein is absent or inactive at the hepatocyte membrane leading to uncontrolled high levels of hepcidin and impaired iron absorption. This study aimed to investigate a 4-year-old boy of sub-Saharan ancestry (Mozambique/Angola), presenting with microcytic hypochromic anemia, low transferrin saturation, normal ferritin, and having a partial response to intravenous iron treatment. He is a -α3.7-thalassemia carrier. TMPRSS6 was screened for variants by Next-Generation Sequencing using Nextera XT libraries in a MiSeq platform (Illumina). Genetic variants found were validated by Sanger sequencing. In silico analyses were performed in HSF, SIFT, Poly-Phen2 and Missense3D softwares. A novel missense mutation (c.871G>A) was found in heterozygosity, in TMPRSS6 exon 8. In silico analysis indicates the conserved amino acid change (G291S) may be damaging to the protein stability. Due to its location in the CUB1 domain, it may also affect the enzyme activation and substrate recognition. Additionally, 3 SNPs previously associated with a greater risk of developing iron deficiency anemia (K253E, V736A and Y739Y) were also identified in TMPRSS6. Although IRIDA is known as an autosomal recessive disease, we conclude that, in this case, the result of a digenic inheritance of the novel damaging mutation (c.871G>A; G291S) and the 3 common modulating SNPs in the same gene and a co-inheritance of the α-thalassemia HBA deletion may lead to an IRIDA-like phenotype. Further functional studies of the mutated protein as well as family studies should be conducted.This work was partially supported by INSA_2013DGH910 and GenomePT (POCI-01-0145-FEDER-022184).info:eu-repo/semantics/publishedVersio

Spontaneous Neonatal Humeral Artery Thromboembolism: a Case Report

info:eu-repo/semantics/publishedVersio

Eficiência do processo de biodigestão em fossa séptica biodigestora inoculada com esterco de ovino.

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Insights into the accessory genome of two pseudomonas aeruginosa clinical isolates using comparative genomics

Recently, we have set a collaboration with Hospital de Braga, located in the North of Portugal, that handles over 600 P. aeruginosa isolates per year, aiming to rouse a holistic research approach to provide relevant information and tools to the clinicians to circumvent the multi-resistance phenomena in P. aeruginosa. Since then, we have set procedures aiming a systematic phenotypic characterization of the clinical isolates and developed strategies for the identification of pathogenicity islands and SNPs among the clinical isolates via comparative genomics. In this context, we have determined the full genome sequence of two clinical isolates using the high-throughput system Illumina Genome Analyzer IIx. These two clinical isolates, named 138244 and 152504, are representatives of allelic sequence types ST175 (widely disseminated and associated with multidrug-resistance) and ST560 (rare allele), respectively. Importantly, under standardized experimental procedures, isolate 138244 did not produce pigments and evidenced an antibiotic pan-resistant phenotype whereas 152504 produced a high amount of pyocyanin pigment and was susceptible to all antibiotics tested. A comparative genomic analysis using the genome sequences of both isolates and of all P. aeruginosa strains deposited in Genbank so far, allowed the identification of the accessory genome content of both isolates. Apparently, isolate 152504 harbors in its genome 254 unique genes, often clustered together in the same locus. Based on the genome annotation information, the pool of unique genes mainly encode several virulence factors, chemical stress resistance systems as well as 183 hypothetical proteins, 45 of which predicted members of the secretome of P. aeruginosa 152504. The accessory genome of 138244 mainly includes genes associated with mobile elements (phages, transposases, integrons) and genes encoding for 160 hypothetical proteins. Currently, research approaches are focused on the functional elucidation of sets of genes encoding hypothetical proteins of both isolates and in the description and characterization of their secretomes.Fundação para a Ciência e a Tecnologia (FCT

A Relevância de um sistema ERP no processo de gerenciamento dos custos: um estudo de caso em uma concessionária de automóveis

TCC (graduação) - Universidade Federal de Santa Catarina, Centro Sócio Econômico, Curso de Ciências ContábeisO aumento da concorrência e as altas exigências do mercado têm reduzido a margem de lucro das empresas ao longo dos anos. Diante deste cenário, as empresas estão mais preocupadas em controlar e buscar alternativas para reduzir seus custos. Nesse sentido, a Gestão de Custos está cada vez mais presente nas organizações, através de ferramentas disponibilizadas pela Contabilidade Gerencial e pela Contabilidade de Custos, que podem auxiliar os gestores no planejamento e tomada de decisões. A fim de obter as informações de custos e as demais informações utilizadas pelos gestores, as empresas de médio e grande porte têm investido fortemente nos sistemas de informações integrados. Conhecidos como Enterprise Resourse Planning (ERP), estes sistemas permitem uma visão completa das operações da empresa, pois podem abranger os processos de todos os seus departamentos, por meio de uma única base de dados. Desta forma, o objetivo da presente pesquisa é identificar quais informações, obtidas por meio de um sistema ERP, podem auxiliar no processo de gerenciamento dos custos de uma concessionária de automóveis. Para alcançar tal objetivo, foram utilizadas a pesquisa bibliográfica, o estudo de caso, a pesquisa e observação participante, e entrevistas semiestruturadas. Após abordar os principais conceitos sobre a Contabilidade Gerencial, Contabilidade de Custos e sobre os sistemas de informações, apresenta-se o estudo de caso, realizado em uma concessionária de automóveis da cidade de Florianópolis, onde foi possível obter as informações necessárias através de entrevistas semi-estruturadas com a gerente administrativa e o gerente do departamento de pós-venda. Por meio da análise dos dados, conclui-se que as informações de custos são tratadas pela empresa de forma distinta para fins contábeis e gerenciais, e que o sistema ERP utilizado, auxilia os gestores a efetuar o controle dos custos, além de atender suas demais necessidades gerenciais. Isso porque disponibiliza diversos relatórios úteis para o planejamento e tomada de decisão, onde é possível ter acesso a informações relevantes como o desempenho das vendas gerais e por departamento, a situação financeira e patrimonial da empresa, a produtividade dos colaboradores, as operações realizadas entre os departamentos, entre outra