Search

MicroRNAs are reported as promising biomarkers for the diagnosis and treatment of breast cancer. miR-1260b is identified as a tumor-associated noncoding microRNA in other cancers, although the role of miR-1260b and its clinical relevance in breast cancer remain unclear. In this study, miR-1260b as a potential prognostic biomarker was observed by univariate and multivariate Cox regression analyses in 102 breast tumor tissues. The tumorigenic role of miR-1260b in terms of proliferation, apoptosis, and migration of breast cancer cells was investigated using gain- and loss-of-function assays in vitro. Additionally, the potential early diagnosis and treatment monitoring marker of miR-1260b was validated in 129 plasma samples. We found that high miR-1260b expression was markedly associated with bulky tumor size, advanced stage, and lymph node invasion. Particularly, the high-miR-1260b-expression group showed shorter overall survival than the low-miR-1260b-expression group. The inhibition of oncogenic miR-1260b induced apoptosis and decreased migration and invasion of MDA-MB-231 cells. CASP8 was revealed as a direct target gene of miR-1260b, which is closely related to apoptosis. Furthermore, miR-1260b expression levels in plasma were significantly higher in patients with breast cancer than in healthy controls. The patients who tested positive for miR-1260b showed 16.3- and 18.2-fold higher risks in the early stage and locally advanced stage, respectively, compared with healthy controls, and the risk was decreased 6.2-fold after neoadjuvant chemotherapy. Taken together, miR-1260b may be a potential novel diagnostic, prognostic, and therapeutic target in breast cancer.

Background Tropomyosin-receptor kinase fused gene (TFG) functions as a regulator of intracellular protein packaging and trafficking at the endoplasmic reticulum exit sites. TFG has recently been proposed as a cause of multisystem proteinopathy. Objectives Here, we describe a Korean family presenting with Parkinson's disease or amyotrophic lateral sclerosis caused by a novel variant of TFG (c.1148 G > A, p.Arg383His). Methods We collected clinical, genetic, dopamine transporter imaging, nerve conduction, and electromyography data from the seven subjects. To verify the pathogenicity of the R383H variant, we studied cell viability and the abnormal aggregation of α-synuclein and TAR DNA-binding protein 43 (TDP-43) in HeLa cells expressing R383H-TFG. Results The clinical phenotypes of the R383H-TFG mutation varied; of the five family members, one had Parkinson's disease, three had subclinical parkinsonism, and one (the proband) had amyotrophic lateral sclerosis. The individual with multiple system atrophy was the proband's paternal cousin, but the TFG genotype was not confirmed due to unavailability of samples. Our in vitro studies showed that R383H-TFG overexpression impaired cell viability. In cells co-expressing R383H-TFG and α-synuclein, insoluble α-synuclein aggregates increased in concentration and were secreted from the cells and co-localized with R383H-TFG. The levels of cytoplasmic insoluble aggregates of TDP-43 increased in HeLa cells expressing R383H-TFG and co-localized with R383H-TFG. Conclusions Clinical and in vitro studies have supported the pathogenic role of the novel TFG mutation in α-synucleinopathy and TDP-43 proteinopathy. These findings expand the phenotypic spectrum of TFG and suggest a pivotal role of endoplasmic reticulum dysfunction during neurodegeneration. © 2021 International Parkinson and Movement Disorder Society.

This study evaluated the gap filler radar as an implementation of the 1.5 km CAPPI (constant altitude plan position indicator) data in Korea. The use of the 1.5 km CAPPI data was an inevitable choice, given the topography of the Korean Peninsula and the location of the radar. However, there still exists a significant portion of beam blockage, and thus there has been debate about the need to introduce the gap filler radar (or, the gap-filler). This study evaluated the possible benefits of introducing gap-fillers over the Korean Peninsula. As a first step, the radar data error was quantified by G/R ratio and root mean square error (RMSE), and the radar data over the Korean Peninsula were evaluated. The gap-fillers were then located where the error was high, and their effect was then evaluated by the decrease in the G/R ratio and RMSE. The mean values of the G/R ratio and RMSE of the 1.5 km CAPPI data over the Korean Peninsula were estimated to be about 2.5 and 4.5 mm h–1, respectively. Even after the mean-field bias correction, the RMSE of the 1.5 km CAPPI data was not decreased and mostly remained very high, around 4.4 mm h–1. Unfortunately, the effect of the gap-filler on the 1.5 km CAPPI data was also found to be very small, just 1–2%. However, the gap-filler could be beneficial, if the lowest elevation angle data were used instead of the 1.5 km CAPPI data. The effect of five gap-fillers could be up to 7% decrease in RMSE.

Recurrent chromosome translocations are the hallmark of many human cancers. A proportion of human extraskeletal myxoid chondrosarcomas (EMCs) are associated with the characteristic chromosomal translocation t(3;9)(q11-12;q22), which results in the formation of a chimeric protein in which the N-terminal domain of the TRK-fused gene (TFG) is fused to the translocated in extraskeletal chondrosarcoma (TEC; also called CHN, CSMF, MINOR, NOR1, and NR4A3) gene. The oncogenic effect of this translocation may be due to the higher transactivation ability of the TFG-TEC chimeric protein; however, downstream target genes of TFG-TEC have not yet been identified. The results presented here, demonstrate that TFG-TEC activates the human β-enolase promoter. EMSAs, ChIP assays, and luciferase reporter assays revealed that TFG-TEC upregulates β-enolase transcription by binding to two NGFI-B response element motifs located upstream of the putative transcription start site. In addition, northern blot, quantitative real-time PCR, and Western blot analyses showed that overexpression of TFG-TEC up-regulated β-enolase mRNA and protein expression in cultured cell lines. Finally, ChIP analyses revealed that TFG-TEC controls the activity of the endogenous β-enolase promoter by promoting histone H3 acetylation. Overall, the results presented here indicate that TFG-TEC triggers a regulatory gene hierarchy implicated in cancer cell metabolism. This finding may aid the development of new therapeutic strategies for the treatment of human EMCs. © 2015 Wiley Periodicals, Inc.

In this study, the correction problem of mean-field bias of radar rain rate was investigated using the concept of linear regression. Three different relationships were reviewed for their slopes to be used as the bias correction factor: Relationship 1 (R1) is based on the conventional linear regression, relationship 2 (R2) is forced to pass the origin and relationship 3 (R3) is the line whose slope is the G/R ratio. In other words, R1 is the regression line connecting the intercept and the mass centre of measurement pairs, R2 is the regression line forced to pass the origin, and R3 is the line connecting the origin and the mass centre. The slopes of all three relationships were reviewed analytically to compare them, and thereby, the effect of zero measurements could be evaluated. Additionally, the effect of using switched independent and dependent variables on the derived slopes was also evaluated. The theoretically derived results were then verified by analysing the rainfall event on 10–11 August 2010 in Korea. Finally, the difference between the bias-corrected radar rain rate and the rain gauge rain rate was quantified by root mean square error and mean error so that it could be used as a measure for the evaluation of bias correction factors. In conclusion, the slope of R2 was found to be the best for the bias correction factor. However, when deciding the slope of this R2, the radar rain rate should be used as the independent variable in the low rain rate region, and the rain gauge rain rate in the high rain rate region above a certain threshold. Copyright © 2013 John Wiley & Sons, Ltd.

For the first time, topological insulator bismuth selenide nanoparticles (Bi2 Se3 NP) are core-shelled with gold (Au@Bi2 Se3 ) i) to represent considerably small-sized (11 nm) plasmonic nanoparticles, enabling accurate bioimaging in the near-infrared region; ii) to substantially improve Bi2 Se3 biocompatibility, iii) water dispersibility, and iv) surface functionalization capability through straightforward gold-thiol interaction. The Au@Bi2 Se3 is subsequently functionalized for v) effective targeting of SH-SY5Y cancer cells, vi) disrupting the endosome/lysosome membrane, vii) traceable delivery of antagomiR-152 and further synergetic oncomiR knockdown and photothermal therapy (PTT). Unprecedentedly, it is observed that the Au shell thickness has a significant impact on evoking the exotic plasmonic features of Bi2 Se3 . The Au@Bi2 Se3 possesses a high photothermal conversion efficiency (35.5%) and a remarkable surface plasmonic effect (both properties are approximately twofold higher than those of 50 nm Au nanoparticles). In contrast to the siRNA/miRNA delivery methods, the antagomiR delivery is based on strand displacement, in which the antagomiR-152 is displaced by oncomiR-152 followed by a surface-enhanced Raman spectroscopy signal drop. This enables both cancer cell diagnosis and in vitro real-time monitoring of the antagomiR release. This selective PTT nanoparticle can also efficiently target solid tumors and undergo in vivo PTT, indicating its potential clinical applications.

The effects of a nonuniform electric field on vapor bubble detachment and heat transfer in subcooled pool boiling from a microheater array are investigated. The heater array faced downward to simulate a -1 g gravity condition and to eliminate the dominant masking effect of the buoyancy force. Experiments were conducted at different subcooling levels for various wall temperatures and electric field magnitudes. A dielectric fluid, FC-72, was used as the working fluid at ambient pressure. The array of 3 x 3 independently controlled microheaters was maintained at constant temperature and the rate of heat transfer from each heater was measured. Bubble images were recorded using a high-speed camera. The electric field was applied between the horizontal downward-facing microheater array, which was grounded, and a spherical, off-axis electrode beneath it. Boiling heat transfer results with and without the electric field are presented in this study. In the absence of the nonuniform electric field, compared to the same bulk fluid temperature and wall superheat settings in the +1 g situation, a much larger primary bubble was formed on the heater array, due to the coalescence of the secondary bubbles that nucleated on the heater array. The vapor bubble remained on the heater array surface and no bubble detachment was observed. With the nonuniform electric field applied, bubbles were lifted and sheared off from the heater array surface. The electric field was able to break up the primary bubble into several smaller bubbles--considerably greater heat transfer enhancement was measured than under similar conditions in +1 g.

Human extraskeletal myxoid chondrosarcoma (EMC) is caused by a chromosomal translocation that involves TEC (translocated in extraskeletal myxoid chondrosarcoma), and either EWS (Ewing's sarcoma) or hTAF(II)68 (human TATA-binding protein-associated factor II 68), which generates EWS-TEC or hTAF(II)68-TEC fusion proteins, respectively. Although there has been a great deal of progress in characterizing EWS-TEC, there is relatively little known about the biological function of hTAF(II)68-TEC. We have examined the functional consequences of the fusion of the amino terminal domain (NTD) of hTAF(II)68 to TEC in EMC. The chimeric gene encodes a nuclear protein that binds DNA with the same sequence specificity as parental TEC. Nuclear localization of hTAF(II)68-TEC was dependent on the DNA binding domain, and we identified a cluster of basic amino acids in the DNA binding domain, KRRR, that specifically mediate the nuclear localization of hTAF(II)68-TEC. The transactivation activity of hTAF(II)68-TEC was higher than TEC towards a known target promoter that contained several TEC binding sites. Finally, deletion analysis of hTAF(II)68-TEC indicated that the hTAF(II)68 NTD, and the AF1 and AF2 domains of hTAF(II)68-TEC are necessary for full transactivation potential. These results suggest that the oncogenic effect of the t(9;17) translocation may be due to the hTAF(II)68-TEC chimeric protein and that fusion of the hTAF(II)68 NTD to the TEC protein produces a gain of function chimeric product.

Phosphorylation of the p53 tumor suppressor at Ser20 (murine Ser23) has been proposed to be critical for disrupting p53 interaction with its negative regulator, MDM2, and allowing p53 stabilization. To determine the importance of Ser23 for the function of p53 in vivo, we generated a mouse in which the endogenous p53 locus was targeted to replace Ser23 with alanine. We show that, in mouse embryonic fibroblasts generated from Ser23 mutant mice, Ser23 mutation did not dramatically reduce IR-induced p53 protein stabilization or p53-dependent cell cycle arrest. However, in Ser23 mutant thymocytes and in the developing cerebellum, p53 stabilization following IR was decreased and resistance to apoptosis was observed. Homozygous Ser23 mutant animals had a reduced lifespan, but did not develop thymic lymphomas or sarcomas that are characteristic of p53−/− mice. Instead, Ser23 mutant animals died between 1 and 2 years with tumors that were most commonly of B-cell lineage. These data support an important role for Ser20/23 phosphorylation in p53 stabilization, apoptosis and tumor suppression.

GPR reflection energy varies with antenna orientation relative to the strike and dip of the reflector. This directional dependence of GPR responses was investigated through numerical experiments and was used to estimate the azimuth of fractures and joints. Three antenna configurations were considered in this study: perpendicular-broadside (YY mode), parallel-broadside (XX mode) and cross-polarization (YX mode). The reflection energy in the cross-polarization mode shows a shape characteristic similar to the strike, regardless of the dip angle. Those in the other two modes show quite different amplitudes from the strike, depending on the dip angle. We have developed a strike-direction-finding scheme using data obtained from the three different modes for the same survey line. The azimuth angle of each reflector was displayed in colour on the GPR profile. This scheme was applied to a field survey at a granite quarry in southern Korea. The GPR profiles showed different images of the reflectors depending on the antenna configuration. The estimated azimuths of reflectors obtained using our scheme matched fairly well with those of known fractures and joints.

Desmoplastic small round cell tumor (DSRCT) is a malignant human cancer that is associated with a specific t(11;22) chromosome translocation, where 265 amino acids from the EWS amino-terminus are fused to the DNA binding domain of the WT1 tumor suppressor gene. We have noticed the presence of several SH3 interacting domains within the amino-terminus of EWS and have assessed the potential of EWS/WT1 to interact with such motifs. We find that EWS/WT1 can associate with the SH3 domain of several proteins, including v-Src. Ectopic expression of v-Src phosphorylates EWS/WT1 in vivo, as well as enhances the transactivation ability of the EWS amino-terminal domain. Structural alteration of the v-Src SH2 or SH3 domains produced mutants that could not interact with EWS/WT1 nor augment the transcriptional properties of EWS. Taken together, our results suggest the possibility that some transcriptional properties of EWS/WT1 may be regulated by a cytoplasmic signaling pathway.

The polymerization of ethylene was studied by using a series of polysiloxane-bridged dinuclear zirconocenes [(SiMe 2 O) n SiMe 2 (C 5 H 4 ) 2 ][(C 9 H 7 )ZrCl 2 ]2 (7, n = 1; 8, n = 2; 9, n = 3), the corresponding mononuclear zirconocene (C 5 H 5 )(C 9 H 7 )ZrCl 2 , 10, and the pentamethylene-bridged dinuclear zirconocene [(CH 2 ) 5 (C 5 H 4 )2][C 9 H 7 )-ZrCl 2 ] 2 , 13. From the polymerization studies using these catalysts it was found that (i) activities of the polysiloxane dinuclear zirconocenes 7-9 were lower than that of the corresponding mononuclear zirconocene 10, (ii ) molecular weights of polyethylenes produced by the dinuclear metallocenes are greater than that of polyethylene produced by the mononuclear metallocene, (iii) the complex 9 holding the longest bridging ligand exhibited the highest activity but produced a polymer having the smallest molecular weight among the polysiloxane-bridged dinuclear zirconocenes, and (iv)the pentamethylene-bridged dinuclear metailocene 13 showed higher activity than the complexes 7-9 and the mononuclear zirconocene 10. The formation of the lowest molecular weight of polyethylene by 9 was attributed to the influence of electron withdrawal caused by the Lewis acid-base interaction between the acidic aluminum of the cocatalyst and the basic oxygen at the polysiloxane linkage as well as the lack of a steric problem. An increase in steric congestion around the metal center led to not only a decrease in catalytic activity due to preventing facile monomer access to the active site but also an increase in the molecular weight of polyethylenes due to supressing β-H elimination.

Dimensional tunability from two dimensions to one dimension is demonstrated for the first time using an artificial superlattice method in synthesizing 1D stripes from 2D layered materials. The 1D confinement of layered Sr2 IrO4 induces distinct 1D quantum-confined electronic states, as observed from optical spectroscopy and resonant inelastic X-ray scattering. This 1D superlattice approach is generalizable to a wide range of layered materials.

The effects of heat, CaCl2, and ethanol on activation of Bacillus spores were determined by monitoring the absorbance decrease during germination in inosine. Bacillus cereus T, B. subtilis A and B. megaterium QM B1551 spores were activated by heat- and CaCl2-treatments. Ethanol activated B. megaterium and B. subtilis spores yet did not activate B. cereus spores. CaCl2- and ethanol-activations were less effective than heat-activation as judged by optimal germination rates and germination extents. The presence of CaCl2 during heat-treatment inhibited heat-activation of all three Bacillus spores without affecting viability or dipicolinic acid content of the spores. The electrophoretic patterns of coat plus outer membrane proteins extracted from Bacillus spores treated with CaCl2 and heat in the presence of CaCl2 were similar to each other and were distinctively different from the patterns of proteins from unactivated spores or the spores treated with heat and/or ethanol.