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71.
72.
Haejeong Heo Jong-Hwan Kim Hyun Jung Lim Jeong-Hwan Kim Miso Kim Jaemoon Koh Joo-Young Im Bo-Kyung Kim Misun Won Ji-Hwan Park Yang-Ji Shin Mi Ran Yun Byoung Chul Cho Yong Sung Kim Seon-Young Kim Mirang Kim 《Experimental & molecular medicine》2022,54(8):1236
Acquired resistance to inhibitors of anaplastic lymphoma kinase (ALK) is a major clinical challenge for ALK fusion-positive non-small-cell lung cancer (NSCLC). In the absence of secondary ALK mutations, epigenetic reprogramming is one of the main mechanisms of drug resistance, as it leads to phenotype switching that occurs during the epithelial-to-mesenchymal transition (EMT). Although drug-induced epigenetic reprogramming is believed to alter the sensitivity of cancer cells to anticancer treatments, there is still much to learn about overcoming drug resistance. In this study, we used an in vitro model of ceritinib-resistant NSCLC and employed genome-wide DNA methylation analysis in combination with single-cell (sc) RNA-seq to identify cytidine deaminase (CDA), a pyrimidine salvage pathway enzyme, as a candidate drug target. CDA was hypomethylated and upregulated in ceritinib-resistant cells. CDA-overexpressing cells were rarely but definitively detected in the naïve cell population by scRNA-seq, and their abundance was increased in the acquired-resistance population. Knockdown of CDA had antiproliferative effects on resistant cells and reversed the EMT phenotype. Treatment with epigenome-related nucleosides such as 5-formyl-2′-deoxycytidine selectively ablated CDA-overexpressing resistant cells via accumulation of DNA damage. Collectively, our data suggest that targeting CDA metabolism using epigenome-related nucleosides represents a potential new therapeutic strategy for overcoming ALK inhibitor resistance in NSCLC.Subject terms: Gene expression, Epigenomics, Non-small-cell lung cancer 相似文献
73.
74.
Hye Jin Heo Hyoung Kyu Kim Jae Boum Youm Sung Woo Cho In-Sung Song Sun Young Lee Tae Hee Ko Nari Kim Kyung Soo Ko Byoung Doo Rhee Jin Han 《Experimental & molecular medicine》2016,48(8):e254
Mitochondria are crucial for maintaining the properties of embryonic stem cells (ESCs) and for regulating their subsequent differentiation into diverse cell lineages, including cardiomyocytes. However, mitochondrial regulators that manage the rate of differentiation or cell fate have been rarely identified. This study aimed to determine the potential mitochondrial factor that controls the differentiation of ESCs into cardiac myocytes. We induced cardiomyocyte differentiation from mouse ESCs (mESCs) and performed microarray assays to assess messenger RNA (mRNA) expression changes at differentiation day 8 (D8) compared with undifferentiated mESCs (D0). Among the differentially expressed genes, Pdp1 expression was significantly decreased (27-fold) on D8 compared to D0, which was accompanied by suppressed mitochondrial indices, including ATP levels, membrane potential, ROS and mitochondrial Ca2+. Notably, Pdp1 overexpression significantly enhanced the mitochondrial indices and pyruvate dehydrogenase activity and reduced the expression of cardiac differentiation marker mRNA and the cardiac differentiation rate compared to a mock control. In confirmation of this, a knockdown of the Pdp1 gene promoted the expression of cardiac differentiation marker mRNA and the cardiac differentiation rate. In conclusion, our results suggest that mitochondrial PDP1 is a potential regulator that controls cardiac differentiation at an early differentiation stage in ESCs. 相似文献
75.
Optical properties of PbS quantum dots (QDs) precipitated inside the oxide glass matrix were investigated. Photoluminescence (PL) from the PbS QDs showed peak wavelengths located at 1170–1680 nm with widths of 150–550 nm. Radii of QDs in glasses were 2.3–4.7 nm depending upon the thermal treatment. Peak wavelengths of PL bands shifted as much as 70 nm as the temperatures and excitation irradiances increased. Calculated effective local temperatures indicated that these shifts of PL spectra were associated with local heating induced by the temperatures and laser beam. 相似文献
76.
Aram Hong Chang Min Choi Han Jun Eun Changseop Jeong Prof. Jiyoung Heo Prof. Nam Joon Kim 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2014,126(30):7939-7942
The CD spectroscopy of a chiral compound in solution yields an average CD value derived from all of the conformations of a chiral molecule. By contrast, CD spectroscopy of cold chiral molecules in the gas phase distinguishes specific conformers of a chiral molecule, but the weak CD effect has limited the practical application of this technique. Reported herein is the first resonant two‐photon ionization CD spectra of ephedrines in a supersonic jet using circularly polarized laser pulses, which were generated by synchronizing the oscillation of the photoelastic modulator with the laser firing. The spectra exhibited well‐resolved CD bands which were specific for the conformations and vibrational modes of each enantiomer. The CD signs and magnitudes of the jet‐cooled chiral molecules were very sensitive to their conformations and thus offered crucial information for determining the three‐dimensional structures of chiral species, as conducted in combination with quantum chemical calculations. 相似文献
77.
Casey P. Johnson Hye-Young Heo Daniel R. Thedens John A. Wemmie Vincent A. Magnotta 《Magnetic resonance imaging》2014
Functional T1ρ mapping has been proposed as a method to assess pH and metabolism dynamics in the brain with high spatial and temporal resolution. The purpose of this work is to describe and evaluate a variant of the spin-locked echo-planar imaging sequence for functional T1ρ mapping at 3 T. The proposed sequence rapidly acquires a time series of T1ρ maps with 4.0 second temporal resolution and 10 slices of volumetric coverage. Simulation, phantom, and in vivo experiments are used to evaluate many aspects of the sequence and its implementation including fidelity of measured T1ρ dynamics, potential confounds to the T1ρ response, imaging parameter tradeoffs, time series analysis approaches, and differences compared to blood oxygen level dependent functional magnetic resonance imaging. It is shown that the high temporal resolution and volumetric coverage of the sequence are obtained with some expense including underestimation of the T1ρ response, sensitivity to T1 dynamics, and reduced signal-to-noise ratio. In vivo studies using a flashing checkerboard functional magnetic resonance imaging paradigm suggest differences between T1ρ and blood oxygen level dependent activation patterns. Possible sources of the functional T1ρ response and potential sequence improvements are discussed. The capability of T1ρ to map whole-brain pH and metabolism dynamics with high temporal and spatial resolution is potentially unique and warrants further investigation and development. 相似文献
78.
Natural convection heat transfer phenomena on horizontal cylinders were investigated experimentally in order to explore the
applicability of analogy experimental method using the copper electroplating system and to visualize the local heat transfer
depending on the angular position and the diameter of the horizontal cylinder. The diameters of the cylinders are varied from
0.01 to 0.15 m, which correspond to the Rayleigh numbers of 1.73 × 107–5.69 × 1011. The measured mass transfer coefficients show good agreements with the existing heat transfer correlations. The patterns
of copper plated on the aluminum cathodes for various Rayleigh numbers reveal and visualize the local heat transfer depending
on the angular position and show good agreement with the works of Kitamura et al. The hydrogen bubbles produced at higher
applied potential visualize the plumes appeared on top region of the cylinders. 相似文献
79.
A neutral Dirac fermion ψ with a nonzero magnetic dipole moment is supplied as a singlet within the context of the standard model and is considered as a dark matter candidate near the electroweak scale (10–1000 GeV). We discuss its dynamics with the ordinary matters through the magnetic dipole moment. The magnetic dipole moment constrained by the relic abundance may be as large as 10−18–10−17e⋅cm. We show that the elastic scattering is due to a spin–spin interaction for the direct detections and the predictions are under experimental exclusion limits of the current direct detectors, XENON10 and CDMS II, and consider the possibility of dark matter detection in the future. 相似文献
80.
Tiefeng Xu Feifei Chen Shixun Dai Xiang Shen Xunsi Wang Qiuhua Nie Chao Liu Kai Xu Jong Heo 《Journal of Non》2011,357(11-13):2219-2222
Tellurite glasses from TeO2–Bi2O3–BaO pseudo-ternary system were prepared using a conventional melt-quenching method and its glass-forming region was determined. A series of glasses were selected and their third-order optical nonlinearities (TONL) were measured by employing the Z-scan method at a wavelength of 800 nm with femtosecond laser pulses. The results showed that glass former Te4+ ions exhibited positive influences on the TONL and glass modifiers Ba2+ ions behaved similarly; low concentrated Bi3+ ions as glass modifiers weakened the nonlinearities, but an excess amount of Bi3+ behaved oppositely. FTIR measurements demonstrated that chemical bonds especially Te–Oeq vibrated at a high energy level remarkably promoted the TONL susceptibility χ(3), and the glass sample with the highest Bi2O3 content exhibited the largest χ(3) value which was due to the presence of BiO3 polyhedra. 相似文献