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Park, Jimin,Du, Ping,Jeon, Jin‐,Kyung,Jang, Gun Hyuk,Hwang, Mintai Peter,Han, Hyung‐,Seop,Park, Kwideok,Lee, Kwan Hyi,Lee, Jee‐,Wook,Jeon, Hojeong,Kim, Yu‐,Chan,Park, Jong Woon WILEY‐VCH Verlag 2015 Angewandte Chemie Vol.127 No.49
<P><B>Abstract</B></P><P>Although the use of reactive oxygen species (ROS) has been extensively studied, current systems employ external stimuli such as light or electrical energy to produce ROS, which limits their practical usage. In this report, biocompatible metals were used to construct a novel electrochemical system that can spontaneously generate H<SUB>2</SUB>O<SUB>2</SUB> without any external light or voltage. The corrosion of Mg transfers electrons to Au‐decorated oxidized Ti in an energetically favorable process, and the spontaneous generation of H<SUB>2</SUB>O<SUB>2</SUB> in an oxygen reduction reaction was revealed to occur at titanium by combined spectroscopic and electrochemical analyses. The controlled release of H<SUB>2</SUB>O<SUB>2</SUB> noticeably enhanced in vitro angiogenesis even in the absence of growth factors. Finally, a new titanium implant prototype was developed by Mg incorporation, and its potential for promoting angiogenesis was demonstrated.</P>
A New Water Oxidation Catalyst: Lithium Manganese Pyrophosphate with Tunable Mn Valency
Park, Jimin,Kim, Hyunah,Jin, Kyoungsuk,Lee, Byung Ju,Park, Yong-Sun,Kim, Hyungsub,Park, Inchul,Yang, Ki Dong,Jeong, Hui-Yun,Kim, Jongsoon,Hong, Koo Tak,Jang, Ho Won,Kang, Kisuk,Nam, Ki Tae American Chemical Society 2014 JOURNAL OF THE AMERICAN CHEMICAL SOCIETY - Vol.136 No.11
<P>The development of a water oxidation catalyst has been a demanding challenge for the realization of overall water-splitting systems. Although intensive studies have explored the role of Mn element in water oxidation catalysis, it has been difficult to understand whether the catalytic capability originates mainly from either the Mn arrangement or the Mn valency. In this study, to decouple these two factors and to investigate the role of Mn valency on catalysis, we selected a new pyrophosphate-based Mn compound (Li<SUB>2</SUB>MnP<SUB>2</SUB>O<SUB>7</SUB>), which has not been utilized for water oxidation catalysis to date, as a model system. Due to the monophasic behavior of Li<SUB>2</SUB>MnP<SUB>2</SUB>O<SUB>7</SUB> with delithiation, the Mn valency of Li<SUB>2-<I>x</I></SUB>MnP<SUB>2</SUB>O<SUB>7</SUB> (<I>x</I> = 0.3, 0.5, 1) can be controlled with negligible change in the crystal framework (e.g., volume change ∼1%). Moreover, inductively coupled plasma mass spectrometry, X-ray photoelectron spectroscopy, ex-situ X-ray absorption near-edge structure, galvanostatic charging–discharging, and cyclic voltammetry analysis indicate that Li<SUB>2-<I>x</I></SUB>MnP<SUB>2</SUB>O<SUB>7</SUB> (<I>x</I> = 0.3, 0.5, 1) exhibits high catalytic stability without additional delithiation or phase transformation. Notably, we observed that, as the averaged oxidation state of Mn in Li<SUB>2-<I>x</I></SUB>MnP<SUB>2</SUB>O<SUB>7</SUB> increases from 2 to 3, the catalytic performance is enhanced in the series Li<SUB>2</SUB>MnP<SUB>2</SUB>O<SUB>7</SUB> < Li<SUB>1.7</SUB>MnP<SUB>2</SUB>O<SUB>7</SUB> < Li<SUB>1.5</SUB>MnP<SUB>2</SUB>O<SUB>7</SUB> < LiMnP<SUB>2</SUB>O<SUB>7</SUB>. Moreover, Li<SUB>2</SUB>MnP<SUB>2</SUB>O<SUB>7</SUB> itself exhibits superior catalytic performance compared with MnO or MnO<SUB>2</SUB>. Our study provides valuable guidelines for developing an efficient Mn-based catalyst under neutral conditions with controlled Mn valency and atomic arrangement.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/jacsat/2014/jacsat.2014.136.issue-11/ja410223j/production/images/medium/ja-2013-10223j_0012.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/ja410223j'>ACS Electronic Supporting Info</A></P>
Crystal Structure of Hypothetical Fructose-Specific EIIB from Escherichia coli
Park, Jimin,Kim, Mi-Sun,Joo, Keehyung,Jhon, Gil-Ja,Berry, Edward A.,Lee, Jooyoung,Shin, Dong Hae Korean Society for Molecular and Cellular Biology 2016 Molecules and cells Vol.39 No.6
We have solved the crystal structure of a predicted fructose-specific enzyme $IIB^{fruc}$ from Escherichia coli ($EcEIIB^{fruc}$) involved in the phosphoenolpyruvate-carbohydrate phosphotransferase system transferring carbohydrates across the cytoplasmic membrane. $EcEIIB^{fruc}$ belongs to a sequence family with more than 5,000 sequence homologues with 25-99% amino-acid sequence identity. It reveals a conventional Rossmann-like ${\alpha}-{\beta}-{\alpha}$ sandwich fold with a unique ${\beta}$-sheet topology. Its C-terminus is longer than its closest relatives and forms an additional ${\beta}$-strand whereas the shorter C-terminus is random coil in the relatives. Interestingly, its core structure is similar to that of enzyme $IIB^{cellobiose}$ from E. coli ($EcIIB^{cel}$) transferring a phosphate moiety. In the active site of the closest $EcEIIB^{fruc}$ homologues, a unique motif CXXGXAHT comprising a P-loop like architecture including a histidine residue is found. The conserved cysteine on this loop may be deprotonated to act as a nucleophile similar to that of $EcIIB^{cel}$. The conserved histidine residue is presumed to bind the negatively charged phosphate. Therefore, we propose that the catalytic mechanism of $EcEIIB^{fruc}$ is similar to that of $EcIIB^{cel}$ transferring phosphoryl moiety to a specific carbohydrate.
Park, Hansoo,Cho, Sung-Yup,Kim, Hyerim,Na, Deukchae,Han, Jee Yun,Chae, Jeesoo,Park, Changho,Park, Ok-Kyoung,Min, Seoyeon,Kang, Jinjoo,Choi, Boram,Min, Jimin,Kwon, Jee Young,Suh, Yun-Suhk,Kong, Seong-H National Academy of Sciences 2015 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.112 No.40
<P><B>Significance</B></P><P>Gastric cancer (GC) is one of the major causes of cancer-related deaths worldwide, but targeted therapy for GC is limited. Here, we identified two druggable targets from genomic alteration profiling of 103 patients with GC from Asia and validated the target suitability using patient-derived GC xenograft models, which recapitulate the tumor biology observed in patients. Combination therapy of irinotecan (standard treatment) with a <I>BCL2L1</I> (<I>BCL2</I>-like 1)-targeted drug was effective in size reduction of GC tumors having amplification of the <I>BCL2L1</I> gene, and genomic mutations of deleted in liver cancer 1 (<I>DLC1</I>) were associated with increased sensitivity to a ROCK inhibitor. Therefore, our study strongly suggests that <I>BCL2L1</I> and <I>DLC1</I> can serve as targets for novel GC therapies.</P><P>Gastric cancer (GC) is the third leading cause of cancer-related deaths worldwide. Recent high-throughput analyses of genomic alterations revealed several driver genes and altered pathways in GC. However, therapeutic applications from genomic data are limited, largely as a result of the lack of druggable molecular targets and preclinical models for drug selection. To identify new therapeutic targets for GC, we performed array comparative genomic hybridization (aCGH) of DNA from 103 patients with GC for copy number alteration (CNA) analysis, and whole-exome sequencing from 55 GCs from the same patients for mutation profiling. Pathway analysis showed recurrent alterations in the Wnt signaling [<I>APC</I>, <I>CTNNB1</I>, and <I>DLC1</I> (deleted in liver cancer 1)], ErbB signaling (<I>ERBB2</I>, <I>PIK3CA</I>, and <I>KRAS</I>), and p53 signaling/apoptosis [<I>TP53</I> and <I>BCL2L1</I> (BCL2-like 1)] pathways. In 18.4% of GC cases (19/103), amplification of the antiapoptotic gene <I>BCL2L1</I> was observed, and subsequently a <I>BCL2L1</I> inhibitor was shown to markedly decrease cell viability in <I>BCL2L1</I>-amplified cell lines and in similarly altered patient-derived GC xenografts, especially when combined with other chemotherapeutic agents. In 10.9% of cases (6/55), mutations in <I>DLC1</I> were found and were also shown to confer a growth advantage for these cells via activation of Rho-ROCK signaling, rendering these cells more susceptible to a ROCK inhibitor. Taken together, our study implicates <I>BCL2L1</I> and <I>DLC1</I> as potential druggable targets for specific subsets of GC cases.</P>
Park, Jimin,Lee, Chany,Lee, Sangjun,Im, Chang-Hwan Elsevier 2019 Computers in biology and medicine Vol.114 No.-
<P><B>Abstract</B></P> <P>Recent experimental studies have shown that static magnetic field can be effective in modulating human brain functions. Following this discovery, a new noninvasive brain stimulation technique was developed: the transcranial static magnetic stimulation (tSMS). Various types of permanent magnets have been used in previous experimental studies, with the aim of validating the effectiveness of tSMS; nevertheless, the spatial distributions of magnetic field generated by these permanent magnets have not been fully investigated. In this study, we compared the distributions of magnetic field on the human cortical surface generated by five different cylindrical magnets (of various dimensions), using the finite element method. Our simulation results demonstrated that the magnitude of magnetic flux density induced in the cortical grey matter of the human brain is proportional to the volume of permanent magnets used, while the magnetic field gradient is not necessarily proportional to the volume of the magnets. Additionally, we showed that the use of magnets with internal holes might not be advantageous. The differences in magnetic field properties induced by various types of permanent magnets suggested that their careful selection, based on magnetic field simulations, might be necessary to increase the effectiveness of tSMS.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Spatial distributions of magnetic field generated by various permanent magnets for tSMS were investigated. </LI> <LI> A new 3D FEM approach that can readily employ different head models was suggested. </LI> <LI> Slight modification in the shape of permanent magnets considerably alters the magnetic field quantities. </LI> <LI> Cylindrical permanent magnet with a hole is disadvantageous over ones without a hole. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>Brief graphical representation of the overall pipeline for the numerical simulations of magnetic field properties in human cortical grey matter induced by five different permanent magnets.</P> <P>[DISPLAY OMISSION]</P>