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- 저자 : Ewers, Brent E. (검색결과 3 건)
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Nils Peters,Esther van Leijsen,Anil M. Tuladhar,Christian Barro,Marek J. Konieczny,Michael Ewers,Philippe Lyrer,Stefan T. Engelter,Jens Kuhle,Marco Duering,Frank-Erik de Leeuw 대한뇌졸중학회 2020 Journal of stroke Vol.22 No.3
Background and Purpose Serum neurofilament light (NfL)-chain is a circulating marker for neuroaxonal injury and is also associated with severity of cerebral small vessel disease (SVD) crosssectionally. Here we explored the association of serum-NfL with imaging and cognitive measures in SVD longitudinally. Methods From 503 subjects with SVD, baseline and follow-up magnetic resonance imaging (MRI) was available for 264 participants (follow-up 8.7±0.2 years). Baseline serum-NfL was measured by an ultrasensitive single-molecule-assay. SVD-MRI-markers including white matter hyperintensity (WMH)-volume, mean diffusivity (MD), lacunes, and microbleeds were assessed at both timepoints. Cognitive testing was performed in 336 participants, including SVD-related domains as well as global cognition and memory. Associations with NfL were assessed using linear regression analyses and analysis of covariance (ANCOVA). Results Serum-NfL was associated with baseline WMH-volume, MD-values and presence of lacunes and microbleeds. SVD-related MRI- and cognitive measures showed progression during follow-up. NfL-levels were associated with future MRI-markers of SVD, including WMH, MD and lacunes. For the latter, this association was independent of baseline lacunes. Furthermore, NfL was associated with incident lacunes during follow-up (P=0.040). NfL-levels were associated with future SVD-related cognitive impairment (processing speed: β=–0.159; 95% confidence interval [CI], –0.242 to –0.068; P=0.001; executive function β=–0.095; 95% CI, –0.170 to –0.007; P=0.033), adjusted for age, sex, education, and depression. Dementia-risk increased with higher NfL-levels (hazard ratio, 5.0; 95% CI, 2.6 to 9.4; P<0.001), however not after adjusting for age. Conclusions Longitudinally, serum-NfL is associated with markers of SVD, especially with incident lacunes, and future cognitive impairment affecting various domains. NfL may potentially serve as an additional marker for disease monitoring and outcome in SVD, potentially capturing both vascular and neurodegenerative processes in the elderly. Keywords Stroke; Dementia; Small vessel diseases; Neurofilament
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Xie, Qiguang,Lou, Ping,Hermand, Victor,Aman, Rashid,Park, Hee Jin,Yun, Dae-Jin,Kim, Woe Yeon,Salmela, Matti Juhani,Ewers, Brent E.,Weinig, Cynthia,Khan, Sarah L.,Schaible, D. Loring P.,McClung, C. Rob National Academy of Sciences 2015 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.112 No.12
<P><B>Significance</B></P><P>The plant circadian clock affects many aspects of growth and development and influences both fitness in natural settings and performance in cultivated conditions. We show that <I>GIGANTEA</I> (<I>GI</I>) underlies a major quantitative trait locus for circadian period in <I>Brassica rapa</I> by fine-mapping, analysis of heterogeneous inbred lines, and transgenic rescue of an <I>Arabidopsis gi-201</I> loss-of-function mutant. Analysis of chimeric and mutated <I>B. rapa GI</I> alleles identified the causal nucleotide polymorphism responsible for the allelic variation in circadian period, cold and salt tolerance, and red light inhibition of hypocotyl elongation. Allelic variation of <I>GI</I> and of clock genes in general offers targets for marker-assisted (molecular) breeding for enhanced stress tolerance and potentially for improved crop yield.</P><P><I>GIGANTEA</I> (<I>GI</I>) was originally identified by a late-flowering mutant in <I>Arabidopsis</I>, but subsequently has been shown to act in circadian period determination, light inhibition of hypocotyl elongation, and responses to multiple abiotic stresses, including tolerance to high salt and cold (freezing) temperature. Genetic mapping and analysis of families of heterogeneous inbred lines showed that natural variation in <I>GI</I> is responsible for a major quantitative trait locus in circadian period in <I>Brassica rapa.</I> We confirmed this conclusion by transgenic rescue of an <I>Arabidopsis gi-201</I> loss of function mutant. The two <I>B. rapa GI</I> alleles each fully rescued the delayed flowering of <I>Arabidopsis gi-201</I> but showed differential rescue of perturbations in red light inhibition of hypocotyl elongation and altered cold and salt tolerance. The <I>B. rapa</I> R500 <I>GI</I> allele, which failed to rescue the hypocotyl and abiotic stress phenotypes, disrupted circadian period determination in <I>Arabidopsis</I>. Analysis of chimeric <I>B. rapa GI</I> alleles identified the causal nucleotide polymorphism, which results in an amino acid substitution (S264A) between the two GI proteins. This polymorphism underlies variation in circadian period, cold and salt tolerance, and red light inhibition of hypocotyl elongation. Loss-of-function mutations of <I>B. rapa GI</I> confer delayed flowering, perturbed circadian rhythms in leaf movement, and increased freezing and increased salt tolerance, consistent with effects of similar mutations in <I>Arabidopsis</I>. Collectively, these data suggest that allelic variation of <I>GI</I>—and possibly of clock genes in general—offers an attractive target for molecular breeding for enhanced stress tolerance and potentially for improved crop yield.</P>
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