70 research outputs found

    Comparative Genomics and Transcriptomics of Propionibacterium acnes

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    The anaerobic Gram-positive bacterium Propionibacterium acnes is a human skin commensal that is occasionally associated with inflammatory diseases. Recent work has indicated that evolutionary distinct lineages of P. acnes play etiologic roles in disease while others are associated with maintenance of skin homeostasis. To shed light on the molecular basis for differential strain properties, we carried out genomic and transcriptomic analysis of distinct P. acnes strains. We sequenced the genome of the P. acnes strain 266, a type I-1a strain. Comparative genome analysis of strain 266 and four other P. acnes strains revealed that overall genome plasticity is relatively low; however, a number of island-like genomic regions, encoding a variety of putative virulence-associated and fitness traits differ between phylotypes, as judged from PCR analysis of a collection of P. acnes strains. Comparative transcriptome analysis of strains KPA171202 (type I-2) and 266 during exponential growth revealed inter-strain differences in gene expression of transport systems and metabolic pathways. In addition, transcript levels of genes encoding possible virulence factors such as dermatan-sulphate adhesin, polyunsaturated fatty acid isomerase, iron acquisition protein HtaA and lipase GehA were upregulated in strain 266. We investigated differential gene expression during exponential and stationary growth phases. Genes encoding components of the energy-conserving respiratory chain as well as secreted and virulence-associated factors were transcribed during the exponential phase, while the stationary growth phase was characterized by upregulation of genes involved in stress responses and amino acid metabolism. Our data highlight the genomic basis for strain diversity and identify, for the first time, the actively transcribed part of the genome, underlining the important role growth status plays in the inflammation-inducing activity of P. acnes. We argue that the disease-causing potential of different P. acnes strains is not only determined by the phylotype-specific genome content but also by variable gene expression

    TXNIP Regulates Peripheral Glucose Metabolism in Humans

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    BACKGROUND: Type 2 diabetes mellitus (T2DM) is characterized by defects in insulin secretion and action. Impaired glucose uptake in skeletal muscle is believed to be one of the earliest features in the natural history of T2DM, although underlying mechanisms remain obscure. METHODS AND FINDINGS: We combined human insulin/glucose clamp physiological studies with genome-wide expression profiling to identify thioredoxin interacting protein (TXNIP) as a gene whose expression is powerfully suppressed by insulin yet stimulated by glucose. In healthy individuals, its expression was inversely correlated to total body measures of glucose uptake. Forced expression of TXNIP in cultured adipocytes significantly reduced glucose uptake, while silencing with RNA interference in adipocytes and in skeletal muscle enhanced glucose uptake, confirming that the gene product is also a regulator of glucose uptake. TXNIP expression is consistently elevated in the muscle of prediabetics and diabetics, although in a panel of 4,450 Scandinavian individuals, we found no evidence for association between common genetic variation in the TXNIP gene and T2DM. CONCLUSIONS: TXNIP regulates both insulin-dependent and insulin-independent pathways of glucose uptake in human skeletal muscle. Combined with recent studies that have implicated TXNIP in pancreatic β-cell glucose toxicity, our data suggest that TXNIP might play a key role in defective glucose homeostasis preceding overt T2DM

    Coevolution between a Family of Parasite Virulence Effectors and a Class of LINE-1 Retrotransposons

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    Parasites are able to evolve rapidly and overcome host defense mechanisms, but the molecular basis of this adaptation is poorly understood. Powdery mildew fungi (Erysiphales, Ascomycota) are obligate biotrophic parasites infecting nearly 10,000 plant genera. They obtain their nutrients from host plants through specialized feeding structures known as haustoria. We previously identified the AVRk1 powdery mildew-specific gene family encoding effectors that contribute to the successful establishment of haustoria. Here, we report the extensive proliferation of the AVRk1 gene family throughout the genome of B. graminis, with sequences diverging in formae speciales adapted to infect different hosts. Also, importantly, we have discovered that the effectors have coevolved with a particular family of LINE-1 retrotransposons, named TE1a. The coevolution of these two entities indicates a mutual benefit to the association, which could ultimately contribute to parasite adaptation and success. We propose that the association would benefit 1) the powdery mildew fungus, by providing a mechanism for amplifying and diversifying effectors and 2) the associated retrotransposons, by providing a basis for their maintenance through selection in the fungal genome

    Gêneses urbanas do colonialismo: síntese de encontros culturais

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    Investigações sobre a gênese das vilas litorâneas de Cananeia, Iguape, São Vicente, Santos, São Sebastião e Ubatuba, no atual estado de São Paulo, evidenciam a significativa contribuição das sociedades indígenas nas ocupações do colonialismo. Presentes alguns séculos antes da chegada dos europeus, elas elegeram essa frente atlântica como habitat, estabelecendo em nichos ecológicos seus lugares de vivência. Tais escolhas balizaram as futuras instalações. Uma recorrência simboliza o encontro cultural entre indígenas e europeus: a articulação do módulo espacial da Matriz com a contiguidade da "rua direita"

    Um mundo novo no Atlântico: marinheiros e ritos de passagem na linha do equador, séculos XV-XX

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    Navigatio in Brasiliam Americae ...

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    Pertenece a la serie 'Grandes Viajes' de BrySign.: a-b4, A-Z4, Aa-Pp4, Qq3.Texto con apost. marg., inic. grab. y ornam., port. calc. arquitectónica.Pt. 2, con port. propia en p. [135]: Navigatio in Brasiliam Americae, qua auctoris navigatio, quae memoriae prodenda in mari viderit, ... / a Ioanne Lerio Burgundo Gallicè primum scripta, deinde latinitate donata ; variis autem figuris illustrata per Theodorum de Bry ... -- Pt. 3, con port. propia en p. 285: Exemplar duarum litterarum, quibus breviter explicantur, et navigatio Nicolai Villagagnonis equitis melitensis, in illam Americae Provinciam, quae vltra Aequatorem ad Tropicum vsque Capricorni extenditur: & mores consuetudinesque Incolarum eius regionis / Scriptae quidem illae ad flumen Ganabara (Lusitanis Rio de Genero dictum) & in Galliam missae à quodam è Villagagnonis domesticis ; nunc vero recens Latio donatae à C.C.A. -- Francofurti : Matthiae Beckeri, 1605
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