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  • 1
    In: Brain, Oxford University Press (OUP), Vol. 146, No. 7 ( 2023-07-03), p. 2957-2974
    Abstract: Reactive astrogliosis is a hallmark of Alzheimer’s disease (AD). However, a clinically validated neuroimaging probe to visualize the reactive astrogliosis is yet to be discovered. Here, we show that PET imaging with 11C-acetate and 18F-fluorodeoxyglucose (18F-FDG) functionally visualizes the reactive astrocyte-mediated neuronal hypometabolism in the brains with neuroinflammation and AD. To investigate the alterations of acetate and glucose metabolism in the diseased brains and their impact on the AD pathology, we adopted multifaceted approaches including microPET imaging, autoradiography, immunohistochemistry, metabolomics, and electrophysiology. Two AD rodent models, APP/PS1 and 5xFAD transgenic mice, one adenovirus-induced rat model of reactive astrogliosis, and post-mortem human brain tissues were used in this study. We further curated a proof-of-concept human study that included 11C-acetate and 18F-FDG PET imaging analyses along with neuropsychological assessments from 11 AD patients and 10 healthy control subjects. We demonstrate that reactive astrocytes excessively absorb acetate through elevated monocarboxylate transporter-1 (MCT1) in rodent models of both reactive astrogliosis and AD. The elevated acetate uptake is associated with reactive astrogliosis and boosts the aberrant astrocytic GABA synthesis when amyloid-β is present. The excessive astrocytic GABA subsequently suppresses neuronal activity, which could lead to glucose uptake through decreased glucose transporter-3 in the diseased brains. We further demonstrate that 11C-acetate uptake was significantly increased in the entorhinal cortex, hippocampus and temporo-parietal neocortex of the AD patients compared to the healthy controls, while 18F-FDG uptake was significantly reduced in the same regions. Additionally, we discover a strong correlation between the patients’ cognitive function and the PET signals of both 11C-acetate and 18F-FDG. We demonstrate the potential value of PET imaging with 11C-acetate and 18F-FDG by visualizing reactive astrogliosis and the associated neuronal glucose hypometablosim for AD patients. Our findings further suggest that the acetate-boosted reactive astrocyte-neuron interaction could contribute to the cognitive decline in AD.
    Type of Medium: Online Resource
    ISSN: 0006-8950 , 1460-2156
    RVK:
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
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    SSG: 12
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  • 2
    Online Resource
    Online Resource
    SAGE Publications ; 2006
    In:  Journal of Information Science Vol. 32, No. 2 ( 2006-04), p. 176-190
    In: Journal of Information Science, SAGE Publications, Vol. 32, No. 2 ( 2006-04), p. 176-190
    Abstract: Exact match queries, wildcard match queries, and k mismatch queries are widely used in various molecular biology applications including the searching of ESTs (Expressed Sequence Tags) and DNA transcription factors. In this paper, we suggest an efficient indexing and processing mechanism for such queries. Our indexing method places a sliding window at every possible location of a DNA sequence and extracts its signature by considering the occurrence frequency of each nucleotide. It then stores a set of signatures using a multi-dimensional index such as the R*-tree. Also, by assigning a weight to each position of a window, it prevents signatures from being concentrated around a few spots in indexing space. Our query processing method converts a query sequence into a multi-dimensional rectangle and searches the index for the signatures overlapping with the rectangle. Experiments with real biological data sets have revealed that the proposed approach is at least 4.4 times, 2.1 times, and several orders of magnitude faster than the previous one in performing exact match, wildcard match, and k-mismatch queries, respectively.
    Type of Medium: Online Resource
    ISSN: 0165-5515 , 1741-6485
    RVK:
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2006
    detail.hit.zdb_id: 439125-1
    detail.hit.zdb_id: 2025062-9
    SSG: 24,1
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  • 3
    Online Resource
    Online Resource
    SAGE Publications ; 2006
    In:  Journal of Information Science Vol. 32, No. 1 ( 2006-02), p. 88-104
    In: Journal of Information Science, SAGE Publications, Vol. 32, No. 1 ( 2006-02), p. 88-104
    Abstract: In molecular biology, DNA sequence matching is one of the most crucial operations. Since DNA databases contain a huge volume of sequences, fast indexes are essential for efficient processing of DNA sequence matching. In this paper, we first point out the problems of the suffix tree, an index structure widely-used for DNA sequence matching, in respect of storage overhead, search performance, and difficulty in seamless integration with DBMS. Then, we propose a new index structure that resolves such problems. The proposed index structure consists of two parts: the primary part realizes the trie as binary bit-string representation without any pointers, and the secondary part helps fast access to the trie's leaf nodes that need to be accessed for post-processing. We also suggest efficient algorithms based on that index for DNA sequence matching. To verify the superiority of the proposed approach, we conduct performance evaluation via a series of experiments. The results reveal that the proposed approach, which requires smaller storage space, can be a few orders of magnitude faster than the suffix tree.
    Type of Medium: Online Resource
    ISSN: 0165-5515 , 1741-6485
    RVK:
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2006
    detail.hit.zdb_id: 439125-1
    detail.hit.zdb_id: 2025062-9
    SSG: 24,1
    Location Call Number Limitation Availability
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  • 4
    Online Resource
    Online Resource
    Elsevier BV ; 2007
    In:  Information Sciences Vol. 177, No. 22 ( 2007-11), p. 4859-4876
    In: Information Sciences, Elsevier BV, Vol. 177, No. 22 ( 2007-11), p. 4859-4876
    Type of Medium: Online Resource
    ISSN: 0020-0255
    RVK:
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2007
    detail.hit.zdb_id: 218760-7
    detail.hit.zdb_id: 1478990-5
    SSG: 24,1
    SSG: 7,11
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  • 5
    Online Resource
    Online Resource
    Elsevier BV ; 2010
    In:  Information Sciences Vol. 180, No. 8 ( 2010-4), p. 1292-1312
    In: Information Sciences, Elsevier BV, Vol. 180, No. 8 ( 2010-4), p. 1292-1312
    Type of Medium: Online Resource
    ISSN: 0020-0255
    RVK:
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2010
    detail.hit.zdb_id: 218760-7
    detail.hit.zdb_id: 1478990-5
    SSG: 24,1
    SSG: 7,11
    Location Call Number Limitation Availability
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