523 research outputs found

    Complex translational regulation of BACE1 involves upstream AUGs and stimulatory elements within the 5′ untranslated region

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    BACE1 is the protease responsible for the production of amyloid-β peptides that accumulate in the brain of Alzheimer's disease (AD) patients. BACE1 expression is regulated at the transcriptional, as well as post-transcriptional level. Very high BACE1 mRNA levels have been observed in pancreas, but the protein and activity were found mainly in brain. An up-regulation of the protein has been described in some AD patients without a change in transcript levels. The features of BACE1 5′ untranslated region (5′ UTR), such as the length, GC content, evolutionary conservation and presence of upstream AUGs (uAUGs), indicate an important regulatory role of this 5′ UTR in translational control. We demonstrate that, in brain and pancreas, almost all of the native BACE1 mRNA contains the full-length 5′ UTR. RNA transfection and in vitro translation show that translation is mainly inhibited by the presence of the uAUGs. We provide a mutational analysis that highlight the second uAUG as the main inhibitory element while mutations of all four uAUGs fully de-repress translation. Furthermore, we have evidence that a sequence within the region 222-323 of the BACE1 5′ UTR has a stimulatory effect on translation that might depend on the presence of trans-acting factors

    Donor contributions to the strengthening of the African peace and security architecture

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    "On the African continent the establishment of the African Union (AU) in the year 2003 was significant in terms of the development of a new African Peace and Security Architecture (APSA). In reaction to the African reform dynamics and the emerging international security agenda, external actors have begun to adjust their instruments and rethink their choices for action. New security concepts as well as recent approaches in development policy and other policy fields explicitly aim to support the peace and security architecture in Africa. When it comes to external support these developments have led to a search for changing approaches spanning foreign, security and development policy. This study sets out to analyse the new APSA in the context of changing concepts for external support to it." (author's abstract
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