Meridianin C inhibits the growth of YD‐10B human tongue cancer cells through macropinocytosis and the down‐regulation of Dickkopf‐related protein‐3

Park, Nam&#x2010,Sook,Park, Yu&#x2010,Kyoung,Ramalingam, Mahesh,Yadav, Anil Kumar,Cho, Hyo&#x2010,Rim,Hong, Victor Sukbong,More, Kunal N.,Bae, Jae&#x2010,Hoon,Bishop&#x2010,Bailey, David,Kano, Junko,N John Wiley and Sons Inc. 2018 Journal of cellular and molecular medicine Vol.22 No.12

<P><B>Abstract</B></P><P>Meridianin C is a marine natural product known for its anti‐cancer activity. At present, the anti‐tumour effects of meridianin C on oral squamous cell carcinoma are unknown. Here, we investigated the effect of meridianin C on the proliferation of four different human tongue cancer cells, YD‐8, YD‐10B, YD‐38 and HSC‐3. Among the cells tested, meridianin C most strongly reduced the growth of YD‐10B cells; the most aggressive and tumorigenic of the cell lines tested. Strikingly, meridianin C induced a significant accumulation of macropinosomes in the YD‐10B cells; confirmed by the microscopic and TEM analysis as well as the entry of FITC‐dextran, which was sensitive to the macropinocytosis inhibitor amiloride. SEM data also revealed abundant long and thin membrane extensions that resemble lamellipodia on the surface of YD‐10B cells treated with meridianin C, pointing out that meridianin C‐induced macropinosomes was the result of macropinocytosis. In addition, meridianin C reduced cellular levels of Dickkopf‐related protein‐3 (DKK‐3), a known negative regulator of macropinocytosis. A role for DKK‐3 in regulating macropinocytosis in the YD‐10B cells was confirmed by siRNA knockdown of endogenous DKK‐3, which led to a partial accumulation of vacuoles and a reduction in cell proliferation, and by exogenous DKK‐3 overexpression, which resulted in a considerable inhibition of the meridianin C‐induced vacuole formation and decrease in cell survival. In summary, this is the first study reporting meridianin C has novel anti‐proliferative effects via macropinocytosis in the highly tumorigenic YD‐10B cell line and the effects are mediated in part through down‐regulation of DKK‐3.</P>

Large‐Deformation Behavior of Honeycomb‐Structured Polymer Sheets as a Function of Polar Angle

Jin, Kwang&#x2010,Yong,Kim, Dae&#x2010,Yoon,Kim, So&#x2010,Eun,Kuo, Shiao&#x2010,Wei,Lee, Joong Hee,Lyu, Min‐,Young,Hwang, Seok&#x2010,Ho,Gent, Alan N.,Nah, Changwoon,Jeong, Kwang&#x2010,Un WILEY‐VCH Verlag 2011 Macromolecular chemistry and physics Vol.212 No.9

<P><B>Abstract</B></P><P>To construct the structure/property relationships of patterned polymer architectures depending on symmetry, the large‐deformation behavior of 2D HSPS with respect to the polar angle was studied. Holes aligned along the HSPS apex were more effective in decreasing tensile force and reducing stress concentration than those located along the plane. On varying the polar angle from 0 to 30°, the tensile force fluctuated up and down like an undamped negative sinusoidal wave with a wavelength of 15°. Additionally, molecular orientations of HSPS were monitored in situ. By comparing experimental measurements with computer simulations, it was concluded that the tensile force depends on the number of holes as well as the orientation of the axes of the honeycomb structure. </P>

Association of thromboxane A2 receptor (<i>TBXA2R</i>) gene polymorphism in patients with aspirin‐intolerant acute urticaria

Palikhe, N. S.,Kim, S.&#x2010,H.,Lee, H.&#x2010,Y.,Kim, J.&#x2010,H.,Ye, Y.&#x2010,M.,Park, H.&#x2010,S. Blackwell Publishing Ltd 2011 Clinical and experimental allergy Vol.41 No.2

<P>Cite this as: N. S. Palikhe, S.‐H. Kim,H.‐Y. Lee, J.‐H. Kim, Y.‐M. Ye and H.‐S. Park, Clinical & Experimental Allergy, 2011 (41) 179–185.</P><P><B>Summary</B></P><P><B>Background </B> The thromboxane A2 receptor (<I>TBXA2R</I>) is a potent broncho‐ and vaso‐constrictor and is associated with leukotriene synthesis. Polymorphisms in the <I>TBXA2R</I> gene have been linked to atopy, asthma, and atopic dermatitis. This study evaluated the association between genetic <I>TBXA2R</I> variants and the development of acetyl salicylic acid (ASA)‐intolerant acute urticaria (AIAU).</P><P><B>Methods </B> AIAU patients (<I>n</I>=167), ASA‐intolerant chronic urticaria (AICU) patients (<I>n</I>=149), and healthy controls (NC) (<I>n</I>=265) were included. All patients were enrolled at Ajou University Hospital in Suwon, Korea. Two <I>TBXA2R</I> polymorphisms (−4684T>C and 795T>C) were genotyped by primer extension using a SNAPshot ddNTP primer extension kit. Luciferase activity was measured using a dual‐luciferase reporter assay kit. An electrophoretic mobility shift assay (EMSA) was performed using a nuclear extract from a human mast cell line (HMC‐1).</P><P><B>Results </B> Genetic association data demonstrated that compared with NC subjects, AIAU patients had a significantly higher frequency of the homozygous TT genotype of <I>TBXA2R</I>−4684T>C (<I>P=</I>0.005, <I>P</I><SUB>corr</SUB>=0.03). No differences were identified between the AICU and the NC groups. Luciferase activity, reflecting promoter activity, was significantly lower with the <I>TBXA2R</I>−4684T‐containing construct than with the −4684C‐containing construct (<I>P</I><0.001); the activity decreased further upon co‐transfection with ETS‐like gene transcription factor‐1 (ELK‐1) (<I>P=</I>0.012). EMSA revealed that the −4684T allele produced a specific shifted band, with a greater affinity than that produced by the −4684C allele.</P><P><B>Conclusion and clinical relevance </B> These results suggest that the <I>TBXA2R</I>−4684T allele may be associated with lower TBXA2R expression, which may contribute to the development of the AIAU phenotype.</P>

Acute necrotic stomatitis (noma) associated with methicillin‐resistant <i>Staphylococcus aureus</i> infection in a newly acquired rhesus macaque (<i>Macaca mulatta</i>)

Lee, J.&#x2010,I.,Kim, K.&#x2010,S.,Oh, B.&#x2010,C.,Kim, N.&#x2010,A.,Kim, I.&#x2010,H.,Park, C.&#x2010,G.,Kim, S.&#x2010,J. Blackwell Publishing Ltd 2011 Journal of medical primatology Vol.40 No.3

<P><B>Abstract</B></P><P><B>Backgroud </B> A newly acquired rhesus macaque was suffering from rapid destruction of the left cheek caused by necrotizing stomatitis.</P><P><B>Methods </B> To restore reconstructive surgery and intensive care with antibiotics, wound protection, wound healing agents, and debridement were applied.</P><P><B>Results </B> <I>Staphylococcus aureus</I> and <I>Enterococcus faecalis</I> were isolated from the culture of the lesion, and the antibiotic susceptibility test revealed methicillin‐resistant <I>Staphylococcus aureus</I> infection. Vancomycin and ampicillin‐sulbactam effectively treated the bacterial infections, and reconstructive surgery was performed once the infection was cleared. Topical application of recombinant human epidermal growth factor (rhEGF) was useful to treat exposed wound of the noma lesion.</P><P><B>Conclusions </B> Simian noma associated with methicillin‐resistant <I>Staphylococcus aureus</I> (MRSA) had not previously been reported in non‐human primates. Although noma associated with MRSA is hard to cure because of its rapid and destructive progress, the aggressive therapy used in this study led to the successful resolution of an acute necrotic stomatitis lesion in a rhesus macaque.</P>

Molecular genetic diversity and population structure of a selected core set in garlic and its relatives using novel SSR markers

Zhao, W.&#x2010,G.,Chung, J.&#x2010,W.,Lee, G.&#x2010,A.,Ma, K.&#x2010,H.,Kim, H.&#x2010,H.,Kim, K.&#x2010,T.,Chung, I.&#x2010,M.,Lee, J.&#x2010,K.,Kim, N.&#x2010,S.,Kim, S.&#x2010,M.,Park, Y.&#x2010 Blackwell Publishing Ltd 2011 Plant breeding Vol.130 No.1

<P> <I>With 7 figures and 6 tables</I> </P><P><B>Abstract</B></P><P>Garlic is widely consumed for its culinary and medical benefits. Six hundred and thirteen accessions of garlic and its relatives with diverse origin were evaluated for genetic diversity at eight recently novel simple sequence repeat loci in this study. A total of 113 alleles were detected, the average allelic richness was 14.1 alleles per locus. Using a heuristic approach, a core set of 95 accessions was successfully developed, which showed 100% coverage of alleles with minimum redundancy. The model‐based structure analysis here revealed the presence of four subpopulations in the selected core set, which was basically consistent with clustering based on the genetic distance. The analysis of molecular variance based on this core set showed that between‐population component of genetic variance is <15.6% in contrast to 84.4% for the within population component. Overall <I>F</I><SUB>ST</SUB> value was 0.1560, indicating a moderate differentiation among the four groups. These results will provide an effective aid for future allele mining, association genetics, mapping and cloning gene(s), germplasm conservation, and improvement programs.</P>

Hypoxic resistance to articular chondrocyte apoptosis – a possible mechanism of maintaining homeostasis of normal articular cartilage

Seol, J.&#x2010,W.,Lee, H.&#x2010,B.,Lee, Y.&#x2010,J.,Lee, Y.&#x2010,H.,Kang, H.&#x2010,s.,Kim, I.&#x2010,s.,Kim, N.&#x2010,S.,Park, S.&#x2010,Y. Blackwell Publishing Ltd 2009 FEBS JOURNAL Vol.276 No.24

<P>Hypoxia and hypoxia‐related genes are important factors in articular chondrocytes during cartilage homeostasis and osteoarthritis. We have investigated the various apoptotic factors that show significance in synovial fluid obtained from normal and experimental osteoarthritic animal models and have evaluated the effect of hypoxia on articular chondrocyte apoptosis induced by these apoptotic factors. Mature beagle dogs underwent surgical transections of ligaments and medial meniscectomies to explore the underlying mechanisms of osteoarthritis. Cartilage and synovial fluid obtained from normal animals and those with osteoarthritis were evaluated via proteasome inhibition, tumour necrosis factor‐related apoptosis‐inducing ligand (TRAIL) protein expression, mitochondrial transmembrane potential and levels of reactive oxygen species. Canine chondrocytes were exposed to the proteasome inhibitor <I>N</I>‐acetyl‐Leu‐Leu‐Norleu‐al and treated with recombinant TRAIL protein under normoxic and hypoxic conditions, measuring chondrocyte cell viability, proteasome activity and levels of apoptotic factors. TRAIL protein expression and ubiquitinated proteins were increased significantly, but the proteasome activity in the synovial fluid of osteoarthritic joints relative to that in normal joints was not. Primary cultured articular chondrocytes cotreated with the proteasome inhibitor and TRAIL progressed to severe apoptosis under normoxic conditions, but the sensitization caused by the combined treatment was suppressed by exposure to hypoxia. Caspase‐8 activation, c‐Jun N‐terminal kinase phosphorylation, the mitochondrial transmembrane potential and the generation of reactive oxygen species involved in cell death regulation were significantly inhibited under hypoxic conditions. These findings suggest that proteasome inhibition and TRAIL may be possible mechanisms in cartilage degradation and joint‐related diseases. Furthermore, the maintenance of hypoxic conditions or therapy with hypoxia‐related genes in the joint may be successful for the treatment of joint‐related diseases, including osteoarthritis.</P>

Crystal structure of the protein A t3g01520, a eukaryotic universal stress protein‐like protein from <i>arabidopsis thaliana</i> in complex with AMP

Kim, Do Jin,Bitto, Eduard,Bingman, Craig A.,Kim, Hyun‐,Jung,Han, Byung Woo,Phillips Jr., George N. John Wiley and Sons Inc. 2015 Proteins Vol.83 No.7

<P><B>ABSTRACT</B></P><P>Members of the universal stress protein (USP) family are conserved in a phylogenetically diverse range of prokaryotes, fungi, protists, and plants and confer abilities to respond to a wide range of environmental stresses. <I>Arabidopsis thaliana</I> contains 44 USP domain‐containing proteins, and USP domain is found either in a small protein with unknown physiological function or in an N‐terminal portion of a multi‐domain protein, usually a protein kinase. Here, we report the first crystal structure of a eukaryotic USP‐like protein encoded from the gene At3g01520. The crystal structure of the protein At3g01520 was determined by the single‐wavelength anomalous dispersion method and refined to an <I>R</I> factor of 21.8% (<I>R</I><SUB>free</SUB> = 26.1%) at 2.5 Å resolution. The crystal structure includes three At3g01520 protein dimers with one AMP molecule bound to each protomer, comprising a Rossmann‐like α/β overall fold. The bound AMP and conservation of residues in the ATP‐binding loop suggest that the protein At3g01520 also belongs to the ATP‐binding USP subfamily members. Proteins 2015; 83:1368–1373. © 2015 The Authors. Proteins: Structure, Function, and Bioinformatics Published by Wiley Periodicals, Inc.</P>

OGLE‐2008‐BLG‐510: first automated real‐time detection of a weak microlensing anomaly – brown dwarf or stellar binary?

Bozza, V.,Dominik, M.,Rattenbury, N. J.,Jørgensen, U. G.,Tsapras, Y.,Bramich, D. M.,Udalski, A.,Bond, I. A.,Liebig, C.,Cassan, A.,Fouqué,, P.,Fukui, A.,Hundertmark, M.,Shin, I.&#x2010,G.,Lee, S. Blackwell Publishing Ltd 2012 MONTHLY NOTICES- ROYAL ASTRONOMICAL SOCIETY Vol.424 No.2

<P><B>ABSTRACT</B></P><P>The microlensing event OGLE‐2008‐BLG‐510 is characterized by an evident asymmetric shape of the peak, promptly detected by the Automated Robotic Terrestrial Exoplanet Microlensing Search (ARTEMiS) system in real time. The skewness of the light curve appears to be compatible both with binary‐lens and binary‐source models, including the possibility that the lens system consists of an M dwarf orbited by a brown dwarf. The detection of this microlensing anomaly and our analysis demonstrate that: (1) automated real‐time detection of weak microlensing anomalies with immediate feedback is feasible, efficient and sensitive, (2) rather common weak features intrinsically come with ambiguities that are not easily resolved from photometric light curves, (3) a modelling approach that finds all features of parameter space rather than just the ‘favourite model’ is required and (4) the data quality is most crucial, where systematics can be confused with real features, in particular small higher order effects such as orbital motion signatures. It moreover becomes apparent that events with weak signatures are a silver mine for statistical studies, although not easy to exploit. Clues about the apparent paucity of both brown‐dwarf companions and binary‐source microlensing events might hide here.</P>

Identification of a novel HLA‐DRB1 allele, DRB1*11:95

Sohn, Y.&#x2010,H.,Oh, H.&#x2010,B.,Heo, Y.&#x2010,S.,Park, N.,Kwon, O.&#x2010,J. Blackwell Publishing Ltd 2011 Tissue antigens Vol.77 No.2

<P>The DRB1*11:95 showed a single nucleotide difference with the DRB1*11:01:01 allele at codon 10 (TAC/TGC).</P>

Reduced expression of the RNA‐binding protein HuD in pancreatic neuroendocrine tumors correlates with low p27^Kip1 levels and poor prognosis

Kim, Chongtae,Jeong, Da Eun,Heo, Sungeun,Ji, Eunbyul,Rho, Jun Gi,Jung, Myeongwoo,Ahn, Sojin,Kim, Ye&#x2010,Jin,Kim, Yong&#x2010,Sung,Nam, Suk Woo,Kulkarni, Rohit N,Lee, Kyoung Bun,Lee, Eun Kyung,Kim, Longman 2018 The Journal of pathology Vol.246 No.2

<P><B>Abstract</B></P><P>For the majority of patients diagnosed with pancreatic neuroendocrine tumors (NETs), there is significant malignant potential with a poor prognosis; however, the molecular abnormalities and pathogenesis of pancreatic NETs have not been firmly established. Here, we report that loss of expression of the RNA‐binding protein HuD correlates with low p27<SUP>Kip1</SUP> (p27) levels and poor prognosis in pancreatic NETs. HuD expression was frequently lost in many human pancreatic NETs, and these pancreatic NETs showed aggressive clinicopathological phenotypes with low p27 levels, increased tumor size, higher World Health Organization grade and pT stage of the tumor, and the presence of angioinvasion. Furthermore, loss of HuD was an independent, progression‐free prognostic factor in multivariate survival analysis. However, the level of HuR, a member of the same Hu protein family as HuD, was not significantly correlated with pancreatic NET size and progression. Mechanistically, HuD enhanced <I>p27</I> mRNA translation by interacting with both the 5′‐untranslated region (UTR) and the 3′‐UTR of <I>p27</I> mRNA, and consequently suppressed cell cycle progression and tumor growth. In addition, HuD competed with miR‐30a‐3p for binding to the 3′‐UTR of <I>p27</I> mRNA, suggesting an interplay between HuD and miR‐30a‐3p in controlling <I>p27</I> translation. Our results identify HuD as a pivotal suppressor of pancreatic NET growth, and suggest that HuD has potential value as a prognostic factor of pancreatic NETs. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.</P>