11 research outputs found

    Legionella pneumophila Secretes a Mitochondrial Carrier Protein during Infection

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    The Mitochondrial Carrier Family (MCF) is a signature group of integral membrane proteins that transport metabolites across the mitochondrial inner membrane in eukaryotes. MCF proteins are characterized by six transmembrane segments that assemble to form a highly-selective channel for metabolite transport. We discovered a novel MCF member, termed Legionella nucleotide carrier Protein (LncP), encoded in the genome of Legionella pneumophila, the causative agent of Legionnaire's disease. LncP was secreted via the bacterial Dot/Icm type IV secretion system into macrophages and assembled in the mitochondrial inner membrane. In a yeast cellular system, LncP induced a dominant-negative phenotype that was rescued by deleting an endogenous ATP carrier. Substrate transport studies on purified LncP reconstituted in liposomes revealed that it catalyzes unidirectional transport and exchange of ATP transport across membranes, thereby supporting a role for LncP as an ATP transporter. A hidden Markov model revealed further MCF proteins in the intracellular pathogens, Legionella longbeachae and Neorickettsia sennetsu, thereby challenging the notion that MCF proteins exist exclusively in eukaryotic organisms

    Finishing the euchromatic sequence of the human genome

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    The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

    A Family-Oriented Software Development Process for Engine Controllers

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    Abstract. This paper presents a family-based software development process for aero-engine control software. The process uses a “family capability ” derived from family analysis of the embedding system. This analysis allows reuse capability to be designed into the process by exploiting prior knowledge of the differences between members of an engine family. The process described follows the traditional software lifecycle. However, the nature of the stages is modified to incorporate the use of the family capability, essentially to allow systematic application of both compositional and generational reuse throughout the development process. The process described was evaluated on a trial project to develop, and subsequently modify, a thurst reverser system for a small aero-engine. Initial results show that this process can reduce effort for both initial and subsequent developments through the use of the family capability

    Chapter 2 - Philology’s roommate: hermeneutics, antiquity, and the seminar

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    This chapter starts from the extraordinary historical circumstance that Schleiermacher and Schlegel, a theologian and classical scholar and philosopher, who both had a huge influence on the development of their disciplines and the institution of the university, shared lodgings as students. It explores their relationship, and the importance of it for their subsequent careers, and expands from this to consider how the seminary, as dominant theological educational institution, was overtaken in the university by the seminar – to explore how both educational forums show similar negotiations of the dynamic between personal, affective relationships and methodological rigour. It thus raises questions about how the public and the private, emotion and objectivity became values of scholarship between philology and theology in the universit

    Chapter 2 - Philology’s roommate: hermeneutics, antiquity, and the seminar

    No full text
    This chapter starts from the extraordinary historical circumstance that Schleiermacher and Schlegel, a theologian and classical scholar and philosopher, who both had a huge influence on the development of their disciplines and the institution of the university, shared lodgings as students. It explores their relationship, and the importance of it for their subsequent careers, and expands from this to consider how the seminary, as dominant theological educational institution, was overtaken in the university by the seminar – to explore how both educational forums show similar negotiations of the dynamic between personal, affective relationships and methodological rigour. It thus raises questions about how the public and the private, emotion and objectivity became values of scholarship between philology and theology in the universit
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