7 research outputs found

    Direct binding of CEP85 to STIL ensures robust PLK4 activation and efficient centriole assembly.

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    Centrosomes are required for faithful chromosome segregation during mitosis. They are composed of a centriole pair that recruits and organizes the microtubule-nucleating pericentriolar material. Centriole duplication is tightly controlled in vivo and aberrations in this process are associated with several human diseases, including cancer and microcephaly. Although factors essential for centriole assembly, such as STIL and PLK4, have been identified, the underlying molecular mechanisms that drive this process are incompletely understood. Combining protein proximity mapping with high-resolution structural methods, we identify CEP85 as a centriole duplication factor that directly interacts with STIL through a highly conserved interaction interface involving a previously uncharacterised domain of STIL. Structure-guided mutational analyses in vivo demonstrate that this interaction is essential for efficient centriolar targeting of STIL, PLK4 activation and faithful daughter centriole assembly. Taken together, our results illuminate a molecular mechanism underpinning the spatiotemporal regulation of the early stages of centriole duplication

    Once and only once: mechanisms of centriole duplication and their deregulation in disease.

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    Centrioles are conserved microtubule-based organelles that form the core of the centrosome and act as templates for the formation of cilia and flagella. Centrioles have important roles in most microtubule-related processes, including motility, cell division and cell signalling. To coordinate these diverse cellular processes, centriole number must be tightly controlled. In cycling cells, one new centriole is formed next to each pre-existing centriole in every cell cycle. Advances in imaging, proteomics, structural biology and genome editing have revealed new insights into centriole biogenesis, how centriole numbers are controlled and how alterations in these processes contribute to diseases such as cancer and neurodevelopmental disorders. Moreover, recent work has uncovered the existence of surveillance pathways that limit the proliferation of cells with numerical centriole aberrations. Owing to this progress, we now have a better understanding of the molecular mechanisms governing centriole biogenesis, opening up new possibilities for targeting these pathways in the context of human disease

    Nutrition in relation to organic aquaculture: Sources and strategies

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    Organic production is a system of farm management and food production that combines best environmental practices, a high level of biodiversity, the preservation of natural resources, the application of high animal welfare standards and a production method in line with the preference of certain consumers for products produced using natural substances and processes. Mie et al. (2017) reviewed existing evidence on the impact of organic food on human health and compared organic versus conventional food production with respect to parameters important to human health. The review emphasised several documented human health benefits associated with organic food production and production methods and concluded that it is likely to be beneficial within the conventional agriculture, for example, in integrated pest management and antibiotics. This chapter covers aspects of current use of formulated feeds, feed composition, aquafeed technology, sustainable alternatives to common feed ingredients, nutritional physiology and general nutritional principles and product quality in the context of the organic aquaculture. It reviews new knowledge and presents research results to update and may modify the criteria and standards for organic aquaculture in relation to nutrition and thus to provide high-quality products for the consumers. This chapter is based on the current European regulation on organic aquaculture, as well as on the proposed revision of the European regulation, which is currently being approved after a long process for getting the agreement of the European Parliament, European Council and the European Commission

    Once and only once: mechanisms of centriole duplication and their deregulation in disease

    No full text
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