ORCID Profile
0000-0002-2763-8907
Current Organisation
Hong Kong University of Science and Technology
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Publisher: Proceedings of the National Academy of Sciences
Date: 05-11-2021
Abstract: The high spatial resolution of three-dimensional (3D) fluorescence imaging of myelinated fibers will greatly facilitate the understanding of 3D neural networks and the pathophysiology of demyelinating diseases. However, existing myelin probes are far from satisfactory because of their low–signal-to-background ratio and poor tissue permeability. We herein developed a near-infrared aggregation-induced emission-active probe, PM-ML, for high-performance myelin imaging. PM-ML could specifically image myelinated fibers in teased sciatic nerves and mouse brain tissues with high contrast, good photostability, and deep penetration depth. PM-ML staining is compatible with several tissue-clearing methods. Its application in assessing myelination for neuropathological studies was also demonstrated using a multiple sclerosis mouse model.
Publisher: Royal Society of Chemistry (RSC)
Date: 2011
DOI: 10.1039/C0MD00241K
Publisher: Springer Science and Business Media LLC
Date: 12-02-2021
DOI: 10.1038/S42003-021-01722-0
Abstract: The dysregulation of gene dosage due to duplication or haploinsufficiency is a major cause of autosomal dominant diseases such as Alzheimer’s disease. However, there is currently no rapid and efficient method for manipulating gene dosage in a human model system such as human induced pluripotent stem cells (iPSCs). Here, we demonstrate a simple and precise method to simultaneously generate iPSC lines with different gene dosages using paired Cas9 nickases. We first generate a Cas9 nickase variant with broader protospacer-adjacent motif specificity to expand the targetability of double-nicking–mediated genome editing. As a proof-of-concept study, we examine the gene dosage effects on an Alzheimer’s disease patient-derived iPSC line that carries three copies of APP ( amyloid precursor protein ). This method enables the rapid and simultaneous generation of iPSC lines with monoallelic, biallelic, or triallelic knockout of APP . The cortical neurons generated from isogenically corrected iPSCs exhibit gene dosage-dependent correction of disease-associated phenotypes of amyloid-beta secretion and Tau hyperphosphorylation. Thus, the rapid generation of iPSCs with different gene dosages using our method described herein can be a useful model system for investigating disease mechanisms and therapeutic development.
Publisher: Society for Neuroscience
Date: 23-06-2010
Publisher: Elsevier BV
Date: 06-2003
Publisher: CSIRO Publishing
Date: 2013
DOI: 10.1071/CH13035
Abstract: Twenty nine novel spiroketal derivatives related to the rubromycins were evaluated for their anti-telomerase activity using the real-time quantitative telomeric repeat lification protocol assay. The parent compound γ-rubromycin exhibited the highest potency against human telomerase activity within the series. Modification of the spiroketal motif by the introduction of heteroatoms and substituents at different positions produced analogues with varying bioactivity. Variation at the isocoumarin subunit of the title compound resulted in weaker activity, indicative of its importance in telomerase inhibition.
Publisher: Wiley
Date: 13-03-2002
DOI: 10.1016/S0014-5793(02)02367-0
Abstract: Ciliary neurotrophic factor (CNTF) is a member of the gp130 family of cytokines. The functional receptor complex of CNTF is composed of the CNTF receptor alpha (CNTFR), gp130 and the leukemia inhibitory factor receptor (LIFR). Three regions on CNTF have been identified as binding sites for its receptors. The ligand-receptor interactions are mediated through the cytokine binding domains (CBDs) and/or the immunoglobulin-like domains of the receptors. However, in the case of CNTF, the precise nature of the protein-protein contacts in the signaling complex has not yet been resolved. In this study, we provide the first demonstration that the membrane distal CBD (CBD1) of LIFR associates in vitro with soluble CNTFR in the absence of CNTF. Moreover, purified CBD1 partially blocks CNTF signaling, but not that of interleukin-6 or LIF, in human embryonal carcinoma cell line Ntera/D1 cells. These data raise the possibility that LIFR has the capability to form a ligand-free complex with CNTFR.
Publisher: Springer Science and Business Media LLC
Date: 2002
Publisher: Wiley
Date: 18-07-2005
DOI: 10.1016/J.FEBSLET.2005.06.061
Abstract: Ciliary neurotrophic factor (CNTF) forms a functional receptor complex containing the CNTF receptor, gp130, and the leukemia inhibitory factor receptor (LIFR). However, the nature and stoichiometry of the receptor-mediated interactions in this complex have not yet been fully resolved. We show here that signaling by CNTF, but not by LIF or oncostatin M (OSM), was abolished in cells overexpressing a LIFR mutant with the N-terminal cytokine binding domain deleted. Our results illustrate molecular differences between the CNTF active receptor complex and those of LIF and OSM and provide further support for the hexameric model of the CNTF receptor complex.
Publisher: Informa UK Limited
Date: 04-2012
DOI: 10.4161/AUTO.19496
Publisher: Informa UK Limited
Date: 02-01-2016
No related grants have been discovered for Nancy Yuk-Yu Ip.