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Singh, Thoudam Debraj,Song, Jaeyoung,Kim, Jina,Chin, Jungwook,Ji, Hyun Dong,Lee, Jae-Eon,Lee, Sang Bong,Yoon, Heeseok,Yu, Ji Hoon,Kim, Sang Kyoon,Yoon, Ghil Suk,Hwang, Hayoung,Lee, Ho Won,Oh, Ji Min,L American Association for Cancer Research 2019 Clinical Cancer Research Vol.25 No.16
<P><B>Purpose:</B></P><P>New strategies to restore sodium iodide symporter (NIS) expression and function in radioiodine therapy–refractive anaplastic thyroid cancers (ATCs) are urgently required. Recently, we reported the regulatory role of estrogen-related receptor gamma (ERRγ) in ATC cell NIS function. Herein, we identified DN200434 as a highly potent (functional IC<SUB>50</SUB> = 0.006 μmol/L), selective, and orally available ERRγ inverse agonist for NIS enhancement in ATC.</P><P><B>Experimental Design:</B></P><P>We sought to identify better ERRγ-targeting ligands and explored the crystal structure of ERRγ in complex with DN200434. After treating ATC cells with DN200434, the change in iodide-handling gene expression, as well as radioiodine avidity was examined. ATC tumor–bearing mice were orally administered with DN200434, followed by <SUP>124</SUP>I-positron emission tomography/CT (PET/CT). For radioiodine therapy, ATC tumor–bearing mice treated with DN200434 were administered <SUP>131</SUP>I (beta ray–emitting therapeutic radioiodine) and then bioluminescent imaging was performed to monitor the therapeutic effects. Histologic analysis was performed to evaluate ERRγ expression status in normal tissue and ATC tissue, respectively.</P><P><B>Results:</B></P><P>DN200434–ERRγ complex crystallographic studies revealed that DN200434 binds to key ERRγ binding pocket residues through four-way interactions. DN200434 effectively upregulated iodide-handling genes and restored radioiodine avidity in ATC tumor lesions, as confirmed by <SUP>124</SUP>I-PET/CT. DN200434 enhanced ATC tumor radioiodine therapy susceptibility, markedly inhibiting tumor growth. Histologic findings of patients with ATC showed higher ERRγ expression in tumors than in normal tissue, supporting ERRγ as a therapeutic target for ATC.</P><P><B>Conclusions:</B></P><P>DN200434 shows potential clinical applicability for diagnosis and treatment of ATC or other poorly differentiated thyroid cancers.</P>
MEGF10 functions as a receptor for the uptake of amyloid-β
Singh, Thoudam Debraj,Park, Seung-Yoon,Bae, Jae-sung,Yun, Youngeun,Bae, Yong-Chul,Park, Rang-Woon,Kim, In-San Elsevier 2010 FEBS letters Vol.584 No.18
<P><B>Abstract</B></P><P>MEGF10 is predominantly expressed in the brain and known to function as a phagocytic receptor. Here, we provide evidence that MEGF10 is involved in the uptake of amyloid-β peptide (Aβ42) in the brain. Overexpression of MEGF10 dramatically increased Aβ42 uptake in Hela cells. Knockdown of endogenous MEGF10 expression significantly decreased Aβ42 uptake in N2A neuroblastoma cells. MEGF10-mediated Aβ uptake is mostly dependent on lipid raft endocytosis pathway. Furthermore, site-directed mutagenesis revealed that the conserved cytoplasmic NPxY and YxxØ motifs are crucial for MEGF10-mediated uptake of Aβ42 peptide. Thus, the identification of the MEGF10 as a functional receptor that mediates the uptake of amyloid-β peptide will help elucidate the molecular mechanisms of amlyoid-β clearance in Alzheimer’s disease.</P><P><B>Structured summary</B></P><P>MINT-7993537: <I>ctxB</I> (uniprotkb:P01556) and <I>Abeta</I> (uniprotkb:P05067) <I>colocalize</I> (MI:0403) by <I>fluorescence microscopy</I> (MI:0416)</P>
Synthesis of functionalized titanium-carboxylate molecular clusters and their catalytic activity
김수연,Debraj Sarkar,김영익,박명환,윤민영,김영조,김민 한국공업화학회 2017 Journal of Industrial and Engineering Chemistry Vol.53 No.-
Various organic functionalities were successfully introduced into titanium-carboxylate molecular clusters, and functional group tolerances of cluster, along with their catalytic activities have been investigated. Amino groups were installed in the para-position relative to the carboxylate, and the secondary functionality was placed at the ortho-position. The molecular structure of the obtained titanium clusters was confirmed by single X-ray crystallography. Overall, functionalized titanium clusters have shown good activities for catalyzing both carbon dioxide cycloadditions and photocatalytic degradation. This study is a good and practical method for the preparation of functionalized titanium materials which can act as catalysts.
Keerthi Katam,Debraj Bhattacharyya,Satoshi Soda,Toshiyuki Shimizu 한국공업화학회 2021 Journal of Industrial and Engineering Chemistry Vol.102 No.-
In this study, the efficiency of a trickling photo-bioreactor (TPBR), seeded with activated sludge andmicroalgae, was evaluated for domestic wastewater treatment. TPBR was operated completely on naturalaeration at 2-, 4-, and 6-h hydraulic retention time (HRT) with a 12:12 h light: dark cycle. The totalorganic carbon (TOC) and total nutrient (TN) removal were negatively affected by decreasing the HRTfrom 6 to 2 h. The TPBR was able to reduce TOC from 93 to 9 mg/L, TN from 34 to 18 mg/L, and phosphorusfrom 23.5 to 4 mg/L at 6-h HRT. The chlorophyll concentration (5 – 7 mg per liter of sponge volume)was observed to be highest in the middle of the reactor. Altogether, 106 organic micropollutants of differentclasses like pharmaceutical, personal care products, pesticides, herbicides, and fungicides weredetected in the influent wastewater sample. However, in the treated effluent, only 17 micropollutantswere detected at 6-h HRT. This shows that the algal-bacterial consortia are capable of removing micropollutantsfrom wastewater. The energy input was 0.06 kWh/kg COD removed which is much less than theconventional activated sludge processes. The results indicate that this novel system is capable of providinga sustainable wastewater treatment solution.
Keerthi Katam,Debraj Bhattacharyya 한국공업화학회 2019 Journal of Industrial and Engineering Chemistry Vol.69 No.-
This study compares the performance of two different systems (i) immobilized microalgae and suspended activated sludge (System A) and (ii) suspended co-culture (System B) in simultaneous treatment and biofuel production from domestic wastewater at different HRTs. The System A showed higher lipid content and carbon, nitrogen and phosphorous removal (40, 88, 91, and 93%) than System B (16, 87, 58, and 80%). C18:0 and C18:1n9t are dominant fatty acids observed in System A and C16:0 and C18:1n9t in System B. The immobilization of microalgae exhibited more benefits than suspended co-culture in terms of treatment and biofuel production.
Graph theoretic methods in the study of structural issues in control
Madhu N. Belur,Debraj Chakraborty 제어로봇시스템학회 2009 제어로봇시스템학회 국제학술대회 논문집 Vol.2009 No.8
This paper addresses questions regarding controllability and observability for ‘generic parameter’ dynamical systems. We use graph theoretic methods and hence the sequestions are answered in a ‘structural sense’. We formulate necessary and sufficient conditions for controllability in terms of suitable maximum matchings in the bipartite graph constructed fro the constraints and variables. The conditions for observability turn out to be similar. We relate the setests to Gilbert ’scontrollability and observability tests.
Lee, Ho Won,Singh, Thoudam Debraj,Lee, Sang‐,Woo,Ha, Jeoung‐,Hee,Rehemtulla, Alnawaz,Ahn, Byeong‐,Cheol,Jeon, Young Hyun,Lee, Jaetae Federation of American Society for Experimental Bi 2014 The FASEB Journal Vol.28 No.7
Natural killer (NK) cell-based immunotherapy is a promising strategy for cancer treatment, and caspase-3 is an important effector molecule in NK cell-mediated apoptosis in cancers. Here, we evaluated the antitumor effects of NK cell-based immunotherapy by serial noninvasive imaging of apoptosis using a caspase-3 sensor in mice with human glioma xenografts. Human glioma cells expressing both a caspase-3 sensor as a surrogate marker for caspase-3 activation and Renilla luciferase (Rluc) as a surrogate marker for cell viability were established and referred to as D54-CR cells. Human NK92 cells were used as effector cells. Treatment with NK92 cells resulted in a time-and effector number-dependent increase in bioluminescence imaging (BLI) activity of the caspase-3 sensor in D54-CR cells in vitro. Caspase-3 activation by NK92 treatment was blocked by Z-VAD treatment in D54-CR cells. Transfusion of NK92 cells induced an increase of the BLI signal by caspase-3 activation in a dose-and time-dependent manner in D54-CR tumor-bearing mice but not in PBS-treated mice. Accordingly, sequential BLI with the Rluc reporter gene revealed marked retardation of tumor growth in the NK92-treatment group but not in the PBS-treatment group. These data suggest that noninvasive imaging of apoptosis with a caspase-3 sensor can be used as an effective tool for evaluation of therapeutic efficacy as well as for optimization of NK cell-based immunotherapy.
Kang, Sungmin,Lee, Ho Won,Jeon, Young Hyun,Singh, Thoudam Debraj,Choi, Yun Ju,Park, Ji Young,Kim, Jun Sung,Lee, Hyunseung,Hong, Kwan Soo,Lee, Inkyu,Jeong, Shin Young,Lee, Sang-Woo,Ha, Jeoung-Hee,Ahn, Elsevier Science 2015 Molecular imaging and biology Vol.17 No.5
<P>This study aimed to track the migration of primary macrophages labeled with near-infrared (NIR) fluorescent magnetic nanoparticles toward chemically induced acute inflammatory lesions in mice and to visualize the effect of anti-inflammatory drugs on macrophage migration using combined fluorescence and magnetic resonance imaging (FLI/MRI).</P>
Ahn, Su-Bi,Lee, Sang Bong,Singh, Thoudam Debraj,Cho, Sung Jin,Kim, Sang Kyoon,Lee, In-Kyu,Jeong, Shin Young,Ahn, Byeong-Cheol,Lee, Jaetae,Lee, Sang-Woo,Jeon, Yong Hyun Neoplasia Press 2017 Translational oncology Vol.10 No.2
<P>Here, we sought to monitor bone marrow–derived dendritic cell (BMDC) migration and antitumor effects using a multimodal reporter imaging strategy in living mice. BMDCs were transduced with retroviral vector harboring human sodium iodide symporter (<I>hNIS</I>, nuclear imaging reporter), firefly <I>luc2</I> (optical imaging reporter), and <I>thy1.1</I> (surrogate marker of <I>NIS</I> and <I>luc2</I>) genes (BMDC/NF cells). No significant differences in biological functions, including cell proliferation, antigen uptake, phenotype expression, and migration ability, were observed between BMDC and BMDC/NF cells. Combined bioluminescence imaging and I-124 positron emission tomography/computed tomography clearly revealed the migration of BMDC/NF cells to draining popliteal lymph nodes at day 7 postinjection. Interestingly, marked tumor protection was observed in mice immunized with TC-1 lysate-pulsed BMDC/NF cells. Our findings suggested that multimodal reporter gene imaging of NIS and luciferase could provide insights into the biological behaviors of dendritic cells in living organisms and could be a useful tool for the optimization of DC-based immunotherapy protocols.</P>