22 research outputs found

    A large scale hearing loss screen reveals an extensive unexplored genetic landscape for auditory dysfunction

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    The developmental and physiological complexity of the auditory system is likely reflected in the underlying set of genes involved in auditory function. In humans, over 150 non-syndromic loci have been identified, and there are more than 400 human genetic syndromes with a hearing loss component. Over 100 non-syndromic hearing loss genes have been identified in mouse and human, but we remain ignorant of the full extent of the genetic landscape involved in auditory dysfunction. As part of the International Mouse Phenotyping Consortium, we undertook a hearing loss screen in a cohort of 3006 mouse knockout strains. In total, we identify 67 candidate hearing loss genes. We detect known hearing loss genes, but the vast majority, 52, of the candidate genes were novel. Our analysis reveals a large and unexplored genetic landscape involved with auditory function

    The mammalian gene function resource: the International Knockout Mouse Consortium.

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    In 2007, the International Knockout Mouse Consortium (IKMC) made the ambitious promise to generate mutations in virtually every protein-coding gene of the mouse genome in a concerted worldwide action. Now, 5 years later, the IKMC members have developed high-throughput gene trapping and, in particular, gene-targeting pipelines and generated more than 17,400 mutant murine embryonic stem (ES) cell clones and more than 1,700 mutant mouse strains, most of them conditional. A common IKMC web portal (www.knockoutmouse.org) has been established, allowing easy access to this unparalleled biological resource. The IKMC materials considerably enhance functional gene annotation of the mammalian genome and will have a major impact on future biomedical research

    The mammalian gene function resource: the international knockout mouse consortium

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    Investigation of Long Term Cycle Stability - First Results of Metal Hydride Composites

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    Reversible reactions of solid powders and hydrogen can be used for hydrogen storage as well as for thermal applications like heat storages or heat conversion systems. For all applications, one of the fundamental prerequisites is the cycle stability of the reaction material and - if required - its bulk structure. At the Institute of Technical Thermodynamics at the German Aerospace Center a test bench to investigate the cycle stability of reversible gas/solid-reactions has been developed and brought into operation (Figure 1, left). The main feature is the possibility to investigate larger quantities of the materials and therefore to investigate also complete structures, e.g. matrixes for heat transfer enhancement. Until now Hydralloy C5 pellets have been cycled more than 1000 times. The bench can be operated automatically, provide temperature levels between 50 and 400°C and a pressure up to 100 bar. The temperature is controlled by a thermostatic bath and allows monitoring any shift in the heat transfer during cycling. The pressure can be increased or decreased quickly so highly dynamic tests can be run. The measurement of temperature and pressure is carried out online at different positions and the overall conversion is measured by an included Sievert’s apparatus. In cooperation with the Fraunhofer Institute for Manufacturing Technology and Advanced Materials IFAM we have recently investigated different compositions of hydralloy C5 and graphite as well as four different pellets of metal hydride with different diameter at the same time. Figure 1, right shows the temperature (T), pressure (p) and pressure difference caused by absorption (DSD) for two cycles of one of these pellets as an example

    Cryo-EM structure of the Shigella type III needle complex.

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    The Type III Secretion Systems (T3SS) needle complex is a conserved syringe-shaped protein translocation nanomachine with a mass of about 3.5 MDa essential for the survival and virulence of many Gram-negative bacterial pathogens. This system is composed of a membrane-embedded basal body and an extracellular needle that deliver effector proteins into host cells. High-resolution structures of the T3SS from different organisms and infection stages are needed to understand the underlying molecular mechanisms of effector translocation. Here, we present the cryo-electron microscopy structure of the isolated Shigella T3SS needle complex. The inner membrane (IM) region of the basal body adopts 24-fold rotational symmetry and forms a channel system that connects the bacterial periplasm with the export apparatus cage. The secretin oligomer adopts a heterogeneous architecture with 16- and 15-fold cyclic symmetry in the periplasmic N-terminal connector and C-terminal outer membrane ring, respectively. Two out of three IM subunits bind the secretin connector via a β-sheet augmentation. The cryo-EM map also reveals the helical architecture of the export apparatus core, the inner rod, the needle and their intervening interfaces
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