Honoring Native American Code Talkers
In: American Indian Culture and Research Journal, Band 35, Heft 3, S. 1-36
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In: American Indian Culture and Research Journal, Band 35, Heft 3, S. 1-36
In: Heritage & Society, Band 2, Heft 1, S. 138-139
ISSN: 2159-0338
In: Great plains research: a journal of natural and social sciences, Band 30, Heft 2, S. 162-162
ISSN: 2334-2463
In: Drug Enforcement and Policy Center, No. 13, October 2019
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Working paper
In: American Indian culture and research journal: AICRJ, Band 40, Heft 2, S. 91-121
In: Plains anthropologist, Band 58, Heft 226, S. 5-30
ISSN: 2052-546X
In: Heritage Management, Band 2, Heft 1, S. 138-139
ISSN: 1940-8439
In: Plains anthropologist, Band 52, Heft 202, S. 229-244
ISSN: 2052-546X
In: The journal of military history, Band 65, Heft 1, S. 207-208
ISSN: 0899-3718
In: The Journal of Military History, Band 65, Heft 1, S. 207
In: Plains anthropologist, Band 46, Heft 177, S. 233-237
ISSN: 2052-546X
In: American Indian Culture and Research Journal, Band 30, Heft 1, S. 131-181
In: https://www.repository.cam.ac.uk/handle/1810/252374
The mechanisms by which mutations in FUS and other RNA binding proteins cause ALS and FTD remain controversial. We propose a model in which low-complexity (LC) domains of FUS drive its physiologically reversible assembly into membrane-free, liquid droplet and hydrogel-like structures. ALS/FTD mutations in LC or non-LC domains induce further phase transition into poorly soluble fibrillar hydrogels distinct from conventional amyloids. These assemblies are necessary and sufficient for neurotoxicity in a C. elegans model of FUS-dependent neurodegeneration. They trap other ribonucleoprotein (RNP) granule components and disrupt RNP granule function. One consequence is impairment of new protein synthesis by cytoplasmic RNP granules in axon terminals, where RNP granules regulate local RNA metabolism and translation. Nuclear FUS granules may be similarly affected. Inhibiting formation of these fibrillar hydrogel assemblies mitigates neurotoxicity and suggests a potential therapeutic strategy that may also be applicable to ALS/FTD associated with mutations in other RNA binding proteins. ; Supported by Canadian Institutes of Health Research (PEF, PStGH), Alzheimer Society of Ontario (PEF, PStGH), Wellcome Trust (PStGH, MEV, CFK, GSK, DR, CEH), Medical Research Council (PStGH, MEV, CFK, GSK), National Institutes of Health Research, Alzheimer Research UK (CFK, GSK), Gates Cambridge Scholarship (JQL), Engineering and Physical Sciences Research Council (CFK, GSK), European Research Council Starting Grant RIBOMYLOME_309545 (GGT), European Research Council under the European Union's Seventh Framework Programme (FP/2007-2013) / ERC Grant Agreement no. 322817 (CEH), and National Institute of Neurological Disorders and Stroke R01 NS07377 (NAS). The authors thank Tom Cech and Roy Parker for helpful discussions. ; This is the final version of the article. It was first available from Elsevier via http://dx.doi.org/10.1016/j.neuron.2015.10.030
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