Identification of a novel <i>FAM83H</i> mutation and microhardness of an affected molar in autosomal dominant hypocalcified amelogenesis imperfecta

Hyun, H.-K.,Lee, S.-K.,Lee, K.-E.,Kang, H.-Y.,Kim, E.-J.,Choung, P.-H.,Kim, J.-W. Blackwell Publishing Ltd 2009 International endodontic journal Vol.42 No.11

<P>Abstract</P><P>Aim </P><P>To determine the underlying molecular genetic aetiology of a family with the hypocalcified form of amelogenesis imperfecta and to investigate the hardness of the enamel and dentine of a known <I>FAM83H</I> mutation.</P><P>Methodology </P><P>Mutational screening of the <I>FAM83H</I> on the basis of candidate gene approach was performed. All exons and exon–intron boundaries was amplified and sequenced. A microhardness test was performed to measure the Vickers microhardness value.</P><P>Results </P><P>A novel nonsense mutation (c.1354C>T, p.Q452X) was identified in the last exon of <I>FAM83H</I>, which resulted in soft, uncalcified enamel. The affected enamel was extremely soft (about 17% of the normal control), but the underlying dentine was as hard as the normal control.</P><P>Conclusions </P><P>Mutational analysis revealed a novel mutation in <I>FAM83H</I> gene. Hardness of dentine was not affected by the mutation, whilst the enamel was extremely soft.</P>

Development of multifunctional metabolic synergists to suppress the evolution of resistance against pyrethroids in insects that blood feed on humans

Hardstone, Melissa C,Strycharz, Joseph P,Kim, Junheon,Park, Il‐,Kwon,Yoon, Kyong Sup,Ahn, Young Joon,Harrington, Laura C,Lee, Si Hyeock,Clark, J Marshall John Wiley Sons, Ltd 2015 Pest Management Science Vol.71 No.6

<P><B>Abstract</B></P><P><B>BACKGROUND</B></P><P>Pyrethroids are the insecticides of choice when exposure to humans is likely, such as occurs in vector and public‐health‐related control programs. Unfortunately, the pyrethroids share a common resistance mechanism with dichlorodiphenyltrichloroethane (DDT), knockdown resistance (<I>kdr</I>), and prior extensive use of DDT has predisposed the pyrethroids to cross‐resistance via <I>kdr</I>. Given the widespread occurrence of <I>kdr</I>, the use of synergists with pyrethroids is considered to be prudent to guard against the selection of multiply resistant insects.</P><P><B>RESULTS</B></P><P>3‐Phenoxybenzyl hexanoate (PBH) was synthesized as a multifunctional pyrethroid synergist that, besides being a surrogate substrate for sequestration/hydrolytic carboxylesterases, now also functions as a substrate for oxidative xenobiotic metabolism. The addition of PBH to permethrin‐treated females of the ISOP450 strain of <I>Culex pipiens quinquefasciatus</I> resulted in a threefold increase in synergism, as judged by the synergistic ratio. Similarly, PBH synergized the action of deltamethrin sixfold on females of the common bed bug, <I>Cimex lectularius</I>, and was 2.8‐fold more synergistic than piperonyl butoxide (PBO).</P><P><B>CONCLUSIONS</B></P><P>PBH synergized the action of both type I and type II pyrethroids in a mosquito vector (<I>Cx. p. quinquefasciatus</I>) and in a public‐health pest, <I>C. lectularius</I>, respectively, indicating a broad spectrum of action on blood‐feeding insects. PBH appears to have residual properties similar to permethrin and is itself non‐toxic, unlike PBO, and therefore should be compatible with existing pyrethroid formulations used for insecticide‐treated nets and home/residential sprays. © 2014 Society of Chemical Industry</P>

MicroRNA signatures associated with immortalization of EBV‐transformed lymphoblastoid cell lines and their clinical traits

Lee, J.‐,E.,Hong, E.‐,J.,Nam, H.‐,Y.,Kim, J.‐,W.,Han, B.‐,G.,Jeon, J.‐,P. Blackwell Publishing Ltd 2011 Cell proliferation Vol.44 No.1

<P><B>Abstract</B></P><P><B>Objective: </B> MicroRNAs (miRNAs) are negative regulators of gene expression that play important roles in cell processes such as proliferation, development and differentiation. Recently, it has been reported that miRNAs are related to development of carcinogenesis. The aim of this study was to identify miRNAs associated with terminal immortalization of Epstein–Barr virus (EBV)‐transformed lymphoblastoid cell line (LCL) and associated clinical traits.</P><P><B>Material and Methods: </B> Hence, we performed miRNA microarray approach with early‐ (p6) and late‐passage (p161) LCLs.</P><P><B>Results and Conclusion: </B> Microarray data showed that nine miRNAs (miR‐20b*, miR‐28‐5p, miR‐99a, miR‐125b, miR‐151‐3p, miR‐151:9.1, miR‐216a, miR‐223* and miR‐1296) were differentially expressed in most LCLs during long‐term culture. In particular, miR‐125b was up‐regulated in all the tested late‐passage LCLs. miR‐99a, miR‐125b, miR‐216a and miR‐1296 were putative negative regulators of <I>RASGRP3</I>, <I>GPR160</I>, <I>PRKCH</I> and <I>XAF1</I>, respectively, which were found to be differentially expressed in LCLs during long‐term culture in a previous study. Linear regression analysis showed that miR‐200a and miR‐296‐3p correlated with triglyceride and HbA1C levels, respectively, suggesting that miRNA signatures of LCLs could provide information on the donor’s health. In conclusion, our study suggests that expression changes of specific miRNAs may be required for terminal immortalization of LCLs. Thus, differentially expressed miRNAs would be a potential marker for completion of cell immortalization during EBV‐mediated tumorigenesis.</P>

High performance photodiodes based on chemically processed Cu doped SnS₂ nanoflakes

Mohan Kumar, G.,Xiao, Fu,Ilanchezhiyan, P.,Yuldashev, Sh.,Madhan Kumar, A.,Cho, H.D.,Lee, D.J.,Kang, T.W. Elsevier 2018 APPLIED SURFACE SCIENCE - Vol.455 No.-

<P><B>Abstract</B></P> <P>In this work, Cu doped SnS<SUB>2</SUB> nanoflakes were synthesized through a simple hydrothermal method. The influence of Cu doping on the structural, optical and electrical properties of SnS<SUB>2</SUB> were investigated in detail. Optical properties explores the Cu doping in SnS<SUB>2</SUB> crystal lattice to result with a red-shift in absorption spectrum, which benefits visible-light absorption. Photodiodes were further fabricated by spin coating Cu doped SnS<SUB>2</SUB> nanoflakes on p-type silicon (Si). Electrical and photoelectrical parameters of Cu doped SnS<SUB>2</SUB> nanoflakes were determined by studying their impedance and current–voltage (I–V) characteristics, respectively. The diodes were found to exhibit excellent rectifying behavior and good sensitivity on par to pristine photodiodes. Impedance results identified the resistance of device to reduce considerably on Cu doping. The enhanced photoelectrical properties of the heterojunctions has been ascribed to Cu ions, which act as effective dopant and contribute to the varied carrier concentration in SnS<SUB>2</SUB>. Finally the obtained results suggest the potential of Cu-doped SnS<SUB>2</SUB> for application in photodetection and sensors applications.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Cu doped SnS<SUB>2</SUB> nanoflakes were synthesized in hexagonal phase. </LI> <LI> Nature of charge carriers/carrier density was determined using Mott-Schottky plots. </LI> <LI> Photodiode based on Cu doped SnS<SUB>2</SUB> nanoflakes were fabricated on p-Si substrate. </LI> <LI> Photodiode revealed improved photocurrent and responsitivity values under illumination. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Serine palmitoyltransferase inhibitor myriocin induces growth inhibition of B16F10 melanoma cells through G₂/M phase arrest

Lee, Y.‐,S.,Choi, K.‐,M.,Choi, M.‐,H.,Ji, S.‐,Y.,Lee, S.,Sin, D.‐,M.,Oh, K.‐,W.,Lee, Y.‐,M.,Hong, J.‐,T.,Yun, Y.‐,P.,Yoo, H.‐,S. Blackwell Publishing Ltd 2011 Cell proliferation Vol.44 No.4

<P><B>Abstract</B></P><P><B>Objectives: </B> Melanoma is the most aggressive form of skin cancer, and it resists chemotherapy. Candidate drugs for effective anti‐cancer treatment have been sought from natural resources. Here, we have investigated anti‐proliferative activity of myriocin, serine palmitoyltransferase inhibitor, in the <I>de novo</I> sphingolipid pathway, and its mechanism in B16F10 melanoma cells.</P><P><B>Material and methods: </B> We assessed cell population growth by measuring cell numbers, DNA synthesis, cell cycle progression, and expression of cell cycle regulatory proteins. Ceramide, sphingomyelin, sphingosine and sphingosine‐1‐phosphate levels were analysed by HPLC.</P><P><B>Results: </B> Myriocin inhibited proliferation of melanoma cells and induced cell cycle arrest in the G<SUB>2</SUB>/M phase. Expressions of cdc25C, cyclin B1 and cdc2 were decreased in the cells after exposure to myriocin, while expression of p53 and p21<SUP>waf1/cip1</SUP> was increased. Levels of ceramide, sphingomyelin, sphingosine and sphingosine‐1‐phosphate in myriocin‐treated cells after 24 h were reduced by approximately 86%, 57%, 75% and 38%, respectively, compared to levels in control cells.</P><P><B>Conclusions: </B> Our results suggest that inhibition of sphingolipid synthesis by myriocin in melanoma cells may inhibit expression of cdc25C or activate expression of p53 and p21<SUP>waf1/cip1</SUP>, followed by inhibition of cyclin B1 and cdc2, resulting in G<SUB>2</SUB>/M arrest of the cell cycle and cell population growth inhibition. Thus, modulation of sphingolipid metabolism by myriocin may be a potential target of mechanism‐based therapy for this type of skin cancer.</P>

Feasibility of proposed single-nucleotide polymorphisms as predictive markers for targeted regimens in metastatic colorectal cancer

Kim, J C,Ha, Y J,Roh, S A,Choi, E Y,Yoon, Y S,Kim, K P,Hong, Y S,Kim, T W,Cho, D H,Kim, S Y,Kim, Y S Nature Publishing Group 2013 The British journal of cancer Vol.108 No.9

<P><B>Background:</B></P><P>Surrogate biomarkers for metastatic colorectal cancer (mCRC) are urgently needed to achieve the best outcomes for targeted therapy.</P><P><B>Methods:</B></P><P>A clinical association analysis was performed to examine the three single-nucleotide polymorphisms (SNPs) that were previously proposed as markers of chemosensitivity to the cetuximab (124 patients) and bevacizumab regimens (100 patients) in mCRC patients. In addition, biological correlations were examined for the candidate SNPs in terms of their regulatory pathway.</P><P><B>Results:</B></P><P>For cetuximab regimens, patients homozygous for the wild-type alleles (<I>GG</I>) of <I>LIFR rs3729740</I> exhibited a 1.9 times greater overall response rate (ORR) and 1.4 months longer progression-free survival (PFS) than those homozygous or heterozygous for the mutant allele (<I>GA</I> and <I>AA</I>; <I>P</I>=0.022 and 0.027, respectively). For bevacizumab regimens, patients homozygous for the minor alleles (<I>TT</I>) of <I>ANXA11 rs1049550</I> exhibited an ORR twice as high as those homozygous or heterozygous for the ancestral allele (<I>CC</I> and <I>CT</I>; <I>P</I>=0.031). Overall response rate gain was achieved up to 10% in patients with wild-type <I>LIFR rs3729740</I> patients either with wild-type <I>KRAS</I> or skin toxicity (<I>P</I>=0.001) respectively. Specifically in clones treated with cetuximab and bevacizumab regimens, active p-ERK and MMP-9 expressions were significantly reduced in clones expressing wild-type <I>LIFR rs3729740</I> (<I>P</I>=0.044) and in those expressing minor-type <I>ANXA11 rs1049550</I> (<I>P</I>=0.007), respectively.</P><P><B>Conclusion:</B></P><P><I>LIFR rs3729740</I> and possibly <I>ANXA11 rs1049550</I> may be useful as biomarkers for predicting whether mCRC patients are sensitive to relevant target regimens, although further validation in large cohorts is needed.</P>

Toward high efficiency organic photovoltaic devices with enhanced thermal stability utilizing P3HT-b-P3PHT block copolymer additives

Zhu, M.,Kim, H.,Jang, Y.,Park, S.,Ryu, D.,Kim, K.,Tang, P.,Qiu, F.,Kim, D.,Peng, J. Royal Society of Chemistry 2016 Journal of Materials Chemistry A Vol.4 No.47

<P>Organic photovoltaics (OPVs) have drawn an extensive amount of attention due to their low cost, processibility and flexibility. However, a cell based on a blend of poly(3-hexylthiophene) (P3HT) and [6,6]-phenyl-C-61-butyric acid methyl ester (PC61BM) has a limited power conversion efficiency (PCE) due to the short exciton diffusion length of similar to 10 nm. We address this issue by designing a series of all-conjugated diblock copolymers, poly(3-hexylthiophene)-b-poly(3-(6-diethylphosphonatohexyl) thiophene) (P3HT-b-P3PHT), intended for use as additives to improve the performance of P3HT:PC61BM-based photovoltaic devices. The PCE of the devices improved from 3.30% to 4.03% with the addition of P3HT-b-P3PHT (3 : 1). The thermal stability of devices with P3HT-b-P3PHT additives improved significantly relative to that of the P3HT:PC61BM reference device, where the devices including a copolymer with a higher P3PHT content exhibited a better thermal stability. It was found that the fill factor (FF) could be regulated by simply varying the block ratio of P3HT-b-P3PHT and played a crucial role in improving both the PCE and the thermal stability. The P3HT-b-P3PHT diffused at the P3HT:PC61BM interface, improved the miscibility between P3HT and PC61BM, optimized the nanoscale morphology of the photoactive layer, and reduced the active layer roughness, all of which improved the FF and thus contributed to an improvement in device performance.</P>

Search for Λc+→ϕpπ0 and branching fraction measurement of Λc+→K−π+pπ0

Pal, B.,Schwartz, A. J.,Adachi, I.,Aihara, H.,Al Said, S.,Asner, D. M.,Aushev, T.,Ayad, R.,Badhrees, I.,Bakich, A. M.,Bansal, V.,Behera, P.,Berger, M.,Bhardwaj, V.,Biswal, J.,Bobrov, A.,Bozek, A.,Bra& American Physical Society 2017 Physical review. D Vol.96 No.5

<P>We have searched for the Cabibbo-suppressed decay Lambda(+)(c) -> pi p(0) in e(+) e(-) collisions using a data sample corresponding to an integrated luminosity of 915 fb(-1). The data were collected by the Belle experiment at the KEKB e(+) e(-) asymmetric-energy collider running at or near the (4S) and (5S) resonances. No significant signal is observed, and we set an upper limit on the branching fraction of B(Lambda(+)(c) -> phi p(0)) < 15.3 x 10(-5) at 90% confidence level. The contribution of nonresonant Lambda(+)(c) -> K+ K- p pi(0) decays is found to be consistent with zero, and the corresponding upper limit on its branching fraction is set to be B(Lambda(+)(c) ->. K+ K- p pi(0))(NR) < 6.3 x 10(-5) at 90% confidence level. We also search for an intermediate hidden-strangeness pentaquark decay P-s(+) -> phi p. We see no evidence for this intermediate decay and set an upper limit on the product branching fraction of B(Lambda(+)(c) -> P-s(+) pi(0)) x B(P-s(+) -> phi p) < 8.3 x 10(-5) at 90% confidence level. Finally, we measure the branching fraction for the Cabibbo-favored decay Lambda(+)(c) -> K- pi(+) p pi(0); the result is B(Lambda(+)(c) -> K- pi(+) p pi(0)) = (4.42 +/- 0.05(stat)+/- 0.12(syst)+/- 0.16(norm))%, which is the most precise measurement to date.</P>

Foxp3 is a key downstream regulator of p53-mediated cellular senescence

Kim, J-E,Shin, J-S,Moon, J-H,Hong, S-W,Jung, D-J,Kim, J H,Hwang, I-Y,Shin, Y J,Gong, E-Y,Lee, D H,Kim, S-M,Lee, E Y,Kim, Y S,Kim, D,Hur, D,Kim, T W,Kim, K-p,Jin, D-H,Lee, W-J Macmillan Publishers Limited 2017 Oncogene Vol.36 No.2

<P>The downstream events and target genes of p53 in the process of senescence are not fully understood. Here, we report a novel function of the forkhead transcription factor Foxp3, which is a key player in mediating T-cell inhibitory functions, in p53-mediated cellular senescence. The overexpression of Foxp3 in mouse embryonic fibroblasts (MEFs) accelerates senescence, whereas Foxp3 knockdown leads to escape from p53-mediated senescence in p53-expressing MEFs. Consistent with these results, Foxp3 expression resulted in the induction of senescence in epithelial cancer cells, including MCF7 and HCT116 cells. Foxp3 overexpression also increased the intracellular levels of reactive oxygen species (ROS). The ROS inhibitor N-acetyl-L-cysteine rescued cells from Foxp3-expression-induced senescence. Furthermore, the elevated ROS levels that accompanied Foxp3 overexpression were paralleled by an increase in p21 expression. Knockdown of p21 in Foxp3-expressing MEFs abrogated the Foxp3-dependent increase in ROS levels, indicating that Foxp3 acts through the induction of p21 and the subsequent ROS elevation to trigger senescence. Collectively, these results suggest that Foxp3 is a downstream target of p53 that is sufficient to induce p21 expression, ROS production and p53-mediated senescence.</P>

Balanced intake of protein and carbohydrate maximizes lifetime reproductive success in the mealworm beetle, Tenebrio molitor (Coleoptera: Tenebrionidae)

Rho, M.S.,Lee, K.P. Pergamon Press 2016 Journal of insect physiology Vol.91 No.-

<P>Recent developments in insect gerontological and nutritional research have suggested that the dietary protein:carbohydrate (P:C) balance is a critical determinant of lifespan and reproduction in many insects. However, most studies investigating this important role of dietary P:C balance have been conducted using dipteran and orthopteran species. In this study, we used the mealworm beetles, Tenebrio molitor L. (Coleoptera: Tenebrionidae), to test the effects of dietary P:C balance on lifespan and reproduction. Regardless of their reproductive status, both male and female beetles had the shortest lifespan at the protein-biased ratio of P:C 5:1. Mean lifespan was the longest at P:C 1:1 for males and at both P:C 1:1 and 1:5 for females. Mating significantly curtailed the lifespan of both males and females, indicating the survival cost of mating. Age-specific egg laying was significantly higher at P:C 1:1 than at the two imbalanced P:C ratios (1:5 or 5:1) at any given age throughout their lives, resulting in the highest lifetime reproductive success at P:C 1:1. When given a choice, beetles actively regulated their intake of protein and carbohydrate to a slightly carbohydrate-biased ratio (P:C 1:1.54-1:1.64 for males and P:C 1:1.31:1.36 for females). The self-selected P:C ratio was significantly higher for females than males, reflecting a higher protein requirement for egg production. Collectively, our results add to a growing body of evidence suggesting the key role played by dietary macronutrient balance in shaping lifespan and reproduction in insects. (C) 2016 Elsevier Ltd. All rights reserved.</P>