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  • 1
    Online Resource
    Online Resource
    Visualizing reactive astrocyte-neuron interaction in Alzheimer’s disease using 11C-acetate and 18F-FDG
    Oxford University Press (OUP) ; 2023
    In:  Brain Vol. 146, No. 7 ( 2023-07-03), p. 2957-2974
    Details
    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
    URL: Article
    DOI: 10.1093/brain/awad037
    RVK:
    XA 10000
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
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  • 2
    Online Resource
    Online Resource
    The Role of the Pars Recta and Pars Oblique of Cricothyroid Muscle in Speech Production
    Elsevier BV ; 2001
    In:  Journal of Voice Vol. 15, No. 4 ( 2001-12), p. 512-518
    Details
    In: Journal of Voice, Elsevier BV, Vol. 15, No. 4 ( 2001-12), p. 512-518
    Type of Medium: Online Resource
    ISSN: 0892-1997
    URL: Article
    DOI: 10.1016/S0892-1997(01)00051-0
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2001
    detail.hit.zdb_id: 2111437-7
    SSG: 7,11
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  • 3
    Online Resource
    Online Resource
    Targeted knockout of a chemokine-like gene increases anxiety and fear responses
    Proceedings of the National Academy of Sciences ; 2018
    In:  Proceedings of the National Academy of Sciences Vol. 115, No. 5 ( 2018-01-30)
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 115, No. 5 ( 2018-01-30)
    Abstract: Emotional responses, such as fear and anxiety, are fundamentally important behavioral phenomena with strong fitness components in most animal species. Anxiety-related disorders continue to represent a major unmet medical need in our society, mostly because we still do not fully understand the mechanisms of these diseases. Animal models may speed up discovery of these mechanisms. The zebrafish is a highly promising model organism in this field. Here, we report the identification of a chemokine-like gene family, samdori ( sam ), and present functional characterization of one of its members, sam2 . We show exclusive mRNA expression of s am2 in the CNS, predominantly in the dorsal habenula, telencephalon, and hypothalamus. We found knockout (KO) zebrafish to exhibit altered anxiety-related responses in the tank, scototaxis and shoaling assays, and increased crh mRNA expression in their hypothalamus compared with wild-type fish. To investigate generalizability of our findings to mammals, we developed a Sam2 KO mouse and compared it to wild-type littermates. Consistent with zebrafish findings, homozygous KO mice exhibited signs of elevated anxiety. We also found bath application of purified SAM2 protein to increase inhibitory postsynaptic transmission onto CRH neurons of the paraventricular nucleus. Finally, we identified a human homolog of SAM2 , and were able to refine a candidate gene region encompassing SAM2 , among 21 annotated genes, which is associated with intellectual disability and autism spectrum disorder in the 12q14.1 deletion syndrome. Taken together, these results suggest a crucial and evolutionarily conserved role of sam2 in regulating mechanisms associated with anxiety.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1707663115
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2018
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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  • 4
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    Online Resource
    Wafer-scale single-crystal hexagonal boron nitride film via self-collimated grain formation
    American Association for the Advancement of Science (AAAS) ; 2018
    In:  Science Vol. 362, No. 6416 ( 2018-11-16), p. 817-821
    Details
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 362, No. 6416 ( 2018-11-16), p. 817-821
    Abstract: Although polycrystalline hexagonal boron nitride (PC-hBN) has been realized, defects and grain boundaries still cause charge scatterings and trap sites, impeding high-performance electronics. Here, we report a method of synthesizing wafer-scale single-crystalline hBN (SC-hBN) monolayer films by chemical vapor deposition. The limited solubility of boron (B) and nitrogen (N) atoms in liquid gold promotes high diffusion of adatoms on the surface of liquid at high temperature to provoke the circular hBN grains. These further evolve into closely packed unimodal grains by means of self-collimation of B and N edges inherited by electrostatic interaction between grains, eventually forming an SC-hBN film on a wafer scale. This SC-hBN film also allows for the synthesis of wafer-scale graphene/hBN heterostructure and single-crystalline tungsten disulfide.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    URL: Article
    DOI: 10.1126/science.aau2132
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2018
    detail.hit.zdb_id: 128410-1
    detail.hit.zdb_id: 2066996-3
    detail.hit.zdb_id: 2060783-0
    SSG: 11
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  • 5
    Online Resource
    Online Resource
    Epidermal Electronics
    American Association for the Advancement of Science (AAAS) ; 2011
    In:  Science Vol. 333, No. 6044 ( 2011-08-12), p. 838-843
    Details
    In: Science, American Association for the Advancement of Science (AAAS), Vol. 333, No. 6044 ( 2011-08-12), p. 838-843
    Abstract: We report classes of electronic systems that achieve thicknesses, effective elastic moduli, bending stiffnesses, and areal mass densities matched to the epidermis. Unlike traditional wafer-based technologies, laminating such devices onto the skin leads to conformal contact and adequate adhesion based on van der Waals interactions alone, in a manner that is mechanically invisible to the user. We describe systems incorporating electrophysiological, temperature, and strain sensors, as well as transistors, light-emitting diodes, photodetectors, radio frequency inductors, capacitors, oscillators, and rectifying diodes. Solar cells and wireless coils provide options for power supply. We used this type of technology to measure electrical activity produced by the heart, brain, and skeletal muscles and show that the resulting data contain sufficient information for an unusual type of computer game controller.
    Type of Medium: Online Resource
    ISSN: 0036-8075 , 1095-9203
    URL: Article
    DOI: 10.1126/science.1206157
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: American Association for the Advancement of Science (AAAS)
    Publication Date: 2011
    detail.hit.zdb_id: 128410-1
    detail.hit.zdb_id: 2066996-3
    detail.hit.zdb_id: 2060783-0
    SSG: 11
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  • 6
    Online Resource
    Online Resource
    Identification of genetic risk factors in the Chinese population implicates a role of immune system in Alzheimer’s disease pathogenesis
    Proceedings of the National Academy of Sciences ; 2018
    In:  Proceedings of the National Academy of Sciences Vol. 115, No. 8 ( 2018-02-20), p. 1697-1706
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 115, No. 8 ( 2018-02-20), p. 1697-1706
    Abstract: Alzheimer’s disease (AD) is a leading cause of mortality among the elderly. We performed a whole-genome sequencing study of AD in the Chinese population. In addition to the variants identified in or around the APOE locus (sentinel variant rs73052335, P = 1.44 × 10 −14 ), two common variants, GCH1 (rs72713460, P = 4.36 × 10 −5 ) and KCNJ15 (rs928771, P = 3.60 × 10 −6 ), were identified and further verified for their possible risk effects for AD in three small non-Asian AD cohorts. Genotype–phenotype analysis showed that KCNJ15 variant rs928771 affects the onset age of AD, with earlier disease onset in minor allele carriers. In addition, altered expression level of the KCNJ15 transcript can be observed in the blood of AD subjects. Moreover, the risk variants of GCH1 and KCNJ15 are associated with changes in their transcript levels in specific tissues, as well as changes of plasma biomarkers levels in AD subjects. Importantly, network analysis of hippocampus and blood transcriptome datasets suggests that the risk variants in the APOE , GCH1 , and KCNJ15 loci might exert their functions through their regulatory effects on immune-related pathways. Taking these data together, we identified common variants of GCH1 and KCNJ15 in the Chinese population that contribute to AD risk. These variants may exert their functional effects through the immune system.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1715554115
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2018
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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  • 7
    Online Resource
    Online Resource
    Nitric Oxide Protects PC12 Cells from Serum Deprivation-Induced Apoptosis by cGMP-Dependent Inhibition of Caspase Signaling
    Society for Neuroscience ; 1999
    In:  The Journal of Neuroscience Vol. 19, No. 16 ( 1999-08-15), p. 6740-6747
    Details
    In: The Journal of Neuroscience, Society for Neuroscience, Vol. 19, No. 16 ( 1999-08-15), p. 6740-6747
    Type of Medium: Online Resource
    ISSN: 0270-6474 , 1529-2401
    URL: Article
    DOI: 10.1523/JNEUROSCI.19-16-06740.1999
    Language: English
    Publisher: Society for Neuroscience
    Publication Date: 1999
    detail.hit.zdb_id: 1475274-8
    SSG: 12
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  • 8
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    Online Resource
    Virulence and transmissibility of H1N2 influenza virus in ferrets imply the continuing threat of triple-reassortant swine viruses
    Proceedings of the National Academy of Sciences ; 2012
    In:  Proceedings of the National Academy of Sciences Vol. 109, No. 39 ( 2012-09-25), p. 15900-15905
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 109, No. 39 ( 2012-09-25), p. 15900-15905
    Abstract: Efficient worldwide swine surveillance for influenza A viruses is urgently needed; the emergence of a novel reassortant pandemic H1N1 (pH1N1) virus in 2009 demonstrated that swine can be the direct source of pandemic influenza and that the pandemic potential of viruses prevalent in swine populations must be monitored. We used the ferret model to assess the pathogenicity and transmissibility of predominant Korean triple-reassortant swine (TRSw) H1N2 and H3N2 influenza viruses genetically related to North American strains. Although most of the TRSw viruses were moderately pathogenic, one [A/Swine/Korea/1204/2009; Sw/1204 (H1N2)] was virulent in ferrets, causing death within 10 d of inoculation, and was efficiently transmitted to naive contact ferrets via respiratory droplets. Although molecular analysis did not reveal known virulence markers, the Sw/1204 virus acquired mutations in hemagglutinin (HA) (Asp-225-Gly) and neuraminidase (NA) (Ser-315-Asn) proteins during the single ferret passage. The contact-Sw/1204 virus became more virulent in mice, replicated efficiently in vitro, extensively infected human lung tissues ex vivo, and maintained its ability to replicate and transmit in swine. Reverse-genetics studies further indicated that the HA 225G and NA 315N substitutions contributed substantially in altering virulence and transmissibility. These findings support the continuing threat of some field TRSw viruses to human and animal health, reviving concerns on the capacity of pigs to create future pandemic viruses. Apart from warranting continued and enhanced global surveillance, this study also provides evidence on the emerging roles of HA 225G and NA 315N as potential virulence markers in mammals.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.1205576109
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2012
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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  • 9
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    Online Resource
    Combinatorial approach for ferroelectric material libraries prepared by liquid source misted chemical deposition method
    Proceedings of the National Academy of Sciences ; 2007
    In:  Proceedings of the National Academy of Sciences Vol. 104, No. 4 ( 2007-01-23), p. 1134-1139
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 104, No. 4 ( 2007-01-23), p. 1134-1139
    Abstract: Combinatorial approach for discovering novel functional materials in the huge diversity of chemical composition and processing conditions has become more important for breakthrough in thin film electronic and energy-conversion devices. The efficiency of combinatorial method depends on the preparation of a reliable high-density composition thin-film library. The physico-chemical properties of each sample on the library should be similar to those of the corresponding samples prepared by one-by-one conventional methods. We successfully developed the combinatorial liquid source misted chemical deposition (LSMCD) method and demonstrated its validity in screening the chemical composition of Bi 3.75 La x Ce 0.25-x Ti 3 O 12 (BLCT) for high remanent polarization ( P r ). LSMCD is a cheap promising combinatorial screening tool. It can control the composition up to ppm level and produce homogeneous multicomponent library. LSMCD method allows us to prepare BLCT thin-film library at the variation of 0.4 mol% of La. Maximum 2 P r is 35 μC/cm −2 at x = 0.21. The intensity of (117) XRD peak is quantitatively related to 2 P r . Newly developed scanning piezoelectric deformation measurement for nano-sized samples using scanning probe microscope (SPM) is also found out to be reliable for determining the relative ranking of P r value rapidly.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.0610146104
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2007
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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  • 10
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    Online Resource
    Sound transmission loss of multi-layered infinite micro-perforated plates
    Acoustical Society of America (ASA) ; 2020
    In:  The Journal of the Acoustical Society of America Vol. 147, No. 1 ( 2020-01-01), p. 508-515
    Details
    In: The Journal of the Acoustical Society of America, Acoustical Society of America (ASA), Vol. 147, No. 1 ( 2020-01-01), p. 508-515
    Abstract: In this paper, the sound transmission loss (STL) of multi-layered infinite micro-perforated plates (MPPs) is studied. A prediction model for the STL of the multi-layered infinite MPPs is developed, where each MPP may or may not have a perforation, and the number of MPPs is arbitrary. When the frequency of interest is well below the critical frequency of the plate such that the effect of flexural vibration can be neglected compared to that of the inertia term, the mass is replaced by an equivalent complex mass. For numerical examples, single-, double- and triple-layered MPPs are studied. As the perforation ratio increases, the magnitude of the equivalent complex mass decreases rapidly, which in turn results in a decrease of the STL. It is observed that for very small perforation ratios, the mass-spring resonance frequencies in double- and triple-layered MPPs move toward a higher frequency as the perforation ratios increase. In addition, the dips at the resonance frequencies become blunt with increases in the perforation ratios due to the artificial damping induced by micro-perforations. It is also found that at a high frequency, the STL shows dips regardless of the perforation ratios when the wavenumber and air gap depths satisfy certain conditions.
    Type of Medium: Online Resource
    ISSN: 0001-4966 , 1520-8524
    URL: Article
    DOI: 10.1121/10.0000600
    RVK:
    EQ 1000
    Language: English
    Publisher: Acoustical Society of America (ASA)
    Publication Date: 2020
    detail.hit.zdb_id: 1461063-2
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