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| 2. |
- Kato, Norihiro, et al.
(author)
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Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation
- 2015
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In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 47:11, s. 1282-1293
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Journal article (peer-reviewed)abstract
- We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10−11 to 5.0 × 10−21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10−6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation.
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| 3. |
- Mun, Seungsoo, et al.
(author)
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Reconfigurable dual-mode optical encryption enabled by block copolymer photonic crystal with micro-imprinted holographic metasurface
- 2023
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In: Materials Today. - : ELSEVIER SCI LTD. - 1369-7021 .- 1873-4103. ; 70, s. 44-56
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Journal article (peer-reviewed)abstract
- Dual-mode optical encryption based on holographic metasurfaces and color components is of great attraction because of their enhanced information security and storage; however, the realization of independently as well as reversibly encodable holographic metasurfaces and color components remains unreported. Herein, we present reconfigurable dual-mode encryptions of structural colors (SC) and holograms, achieved through stimuli-responsive block copolymer (BCP) photonic crystals (PCs) with micro-imprinted holographic metasurfaces. Holographic images appear when the micro-imprinted BCP PCs, consisting of self-assembled alternating lamellae of two dielectrics, are exposed to an incident laser. A characteristic SC develops in the visible range when the imprinted film is immersed in a liquid agent that can swell one of the dielectrics, allowing for dual-mode holographic and SC encodings in the solid and liquid states, respectively. The dual-mode optical encoding is reconfigured. The holographic image can be erased and replaced with another micropattern, while preserving the SC. Moreover, an SC, set by crosslinking of the swellable lamellae, is reset by chemical de-crosslinking and subsequent transient re-crosslinking, enabling the SC reconfigurability of the BCP PC film. A prototype of a high-security reconfigurable dual encryption has been developed, wherein true information is decrypted when holographic passwords are confirmed with full-color visible SC passwords.
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| 4. |
- Wen, Wanqing, et al.
(author)
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Genome-wide association studies in East Asians identify new loci for waist-hip ratio and waist circumference
- 2016
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In: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Journal article (peer-reviewed)abstract
- Sixty genetic loci associated with abdominal obesity, measured by waist circumference (WC) and waist-hip ratio (WHR), have been previously identified, primarily from studies conducted in Europeanancestry populations. We conducted a meta-analysis of associations of abdominal obesity with approximately 2.5 million single nucleotide polymorphisms (SNPs) among 53,052 (for WC) and 48,312 (for WHR) individuals of Asian descent, and replicated 33 selected SNPs among 3,762 to 17,110 additional individuals. We identified four novel loci near the EFEMP1, ADAMTSL3, CNPY2, and GNAS genes that were associated with WC after adjustment for body mass index (BMI); two loci near the NID2 and HLA-DRB5 genes associated with WHR after adjustment for BMI, and three loci near the CEP120, TSC22D2, and SLC22A2 genes associated with WC without adjustment for BMI. Functional enrichment analyses revealed enrichment of corticotropin-releasing hormone signaling, GNRH signaling, and/or CDK5 signaling pathways for those newly-identified loci. Our study provides additional insight on genetic contribution to abdominal obesity.
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| 5. |
- Kim, Yonghyo, et al.
(author)
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Identification and validation of VEGFR2 kinase as a target of voacangine by a systematic combination of DARTS and MSI
- 2020
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In: Biomolecules. - : MDPI AG. - 2218-273X. ; 10:4
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Journal article (peer-reviewed)abstract
- Although natural products are an important source of drugs and drug leads, identification and validation of their target proteins have proven difficult. Here, we report the development of a systematic strategy for target identification and validation employing drug affinity responsive target stability (DARTS) and mass spectrometry imaging (MSI) without modifying or labeling natural compounds. Through a validation step using curcumin, which targets aminopeptidase N (APN), we successfully standardized the systematic strategy. Using label-free voacangine, an antiangiogenic alkaloid molecule as the model natural compound, DARTS analysis revealed vascular endothelial growth factor receptor 2 (VEGFR2) as a target protein. Voacangine inhibits VEGFR2 kinase activity and its downstream signaling by binding to the kinase domain of VEGFR2, as was revealed by docking simulation. Through cell culture assays, voacangine was found to inhibit the growth of glioblastoma cells expressing high levels of VEGFR2. Specific localization of voacangine to tumor compartments in a glioblastoma xenograft mouse was revealed by MSI analysis. The overlap of histological images with the MSI signals for voacangine was intense in the tumor regions and showed colocalization of voacangine and VEGFR2 in the tumor tissues by immunofluorescence analysis of VEGFR2. The strategy employing DARTS and MSI to identify and validate the targets of a natural compound as demonstrated for voacangine in this study is expected to streamline the general approach of drug discovery and validation using other biomolecules including natural products.
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| 6. |
- Papawassiliou, Wassilios, et al.
(author)
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Crystal and electronic facet analysis of ultrafine Ni2P particles by solid-state NMR nanocrystallography
- 2021
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Journal article (peer-reviewed)abstract
- Structural and morphological control of crystalline nanoparticles is crucial in the field of heterogeneous catalysis and the development of reaction specific catalysts. To achieve this, colloidal chemistry methods are combined with ab initio calculations in order to define the reaction parameters, which drive chemical reactions to the desired crystal nucleation and growth path. Key in this procedure is the experimental verification of the predicted crystal facets and their corresponding electronic structure, which in case of nanostructured materials becomes extremely difficult. Here, by employing P-31 solid-state nuclear magnetic resonance aided by advanced density functional theory calculations to obtain and assign the Knight shifts, we succeed in determining the crystal and electronic structure of the terminating surfaces of ultrafine Ni2P nanoparticles at atomic scale resolution. Our work highlights the potential of ssNMR nanocrystallography as a unique tool in the emerging field of facet-engineered nanocatalysts. Structural and morphological control of crystalline nanoparticles is crucial in heterogeneous catalysis. Applying DFT-assisted solid-state NMR spectroscopy, we determine the surface crystal and electronic structure of Ni2P nanoparticles, unveiling NMR nanocrystallography as an emerging tool in facet-engineered nanocatalysts.
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| 7. |
- Sakornsakolpat, Phuwanat, et al.
(author)
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Genetic landscape of chronic obstructive pulmonary disease identifies heterogeneous cell-type and phenotype associations
- 2019
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 51:3, s. 494-505
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Journal article (peer-reviewed)abstract
- Chronic obstructive pulmonary disease (COPD) is the leading cause of respiratory mortality worldwide. Genetic risk loci provide new insights into disease pathogenesis. We performed a genome-wide association study in 35,735 cases and 222,076 controls from the UK Biobank and additional studies from the International COPD Genetics Consortium. We identified 82 loci associated with P < 5 x 10-8; 47 of these were previously described in association with either COPD or population-based measures of lung function. Of the remaining 35 new loci, 13 were associated with lung function in 79,055 individuals from the SpiroMeta consortium. Using gene expression and regulation data, we identified functional enrichment of COPD risk loci in lung tissue, smooth muscle, and several lung cell types. We found 14 COPD loci shared with either asthma or pulmonary fibrosis. COPD genetic risk loci clustered into groups based on associations with quantitative imaging features and comorbidities. Our analyses provide further support for the genetic susceptibility and heterogeneity of COPD.
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| 8. |
- Jung, Young-Eun, et al.
(author)
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The Korean version of the Connor-Davidson Resilience Scale: An extended validation
- 2012
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In: Stress and Health. - : John Wiley & Sons. - 1532-3005 .- 1532-2998. ; 28:4, s. 319-326
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Journal article (peer-reviewed)abstract
- The Connor–Davidson Resilience Scale (CD‐RISC) is a brief self‐rating questionnaire for measuring resilience. The aims of the present study were to describe the development of a Korean version of the CD‐RISC (K‐CD‐RISC) and to more firmly establish its psychometric properties in terms of reliability and validity. The participants consisted of a general population sample (n = 194) and psychiatric outpatients (n = 127) with non‐psychotic mood or anxiety disorders. The K‐CD‐RISC score means (standard deviation) were 65.9 (13.6) in the general population and 50.4 (20.5) in the psychiatric outpatients. The mean score of the general population was significantly higher than that of the psychiatric outpatients. Exploratory factor analysis revealed five factors, and the obtained factor structure was verified through confirmatory factor analysis. In the general population, the Cronbach's α coefficient of the K‐CD‐RISC was found to be 0.92. Greater resilience was found to be associated with less perceived stress, anxiety and depression and with higher levels of positive affect and purpose in life. Taken together, our findings suggest that the K‐CD‐RISC has good psychometric properties and is a valid and reliable tool for assessing resilience.
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| 9. |
- Kim, Dongyoung, et al.
(author)
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FK506, an Immunosuppressive Drug, Induces Autophagy by Binding to the V-ATPase Catalytic Subunit A in Neuronal Cells
- 2017
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In: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 16:1, s. 55-64
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Journal article (peer-reviewed)abstract
- The drug FK506 (tacrolimus, fujimycin) exerts its immunosuppressive effects by regulating the nuclear factor of the activated T-cell (NFAT) family of transcription factors. However, FK506 also exhibits neuroprotective effects, but its direct target proteins that mediate these effects have not been determined. To identify the target proteins responsible for FK506's neuroprotective effects, the drug affinity responsive target stability (DARTS) method was performed using label-free FK506, and LC-MS/MS analysis of the FK506-treated proteome was also performed. Using DARTS and LC-MS/MS analyses in combination with reference studies, V-ATPase catalytic subunit A (ATP6V1A) was identified as a new target protein of FK506. The biological relevance of ATP6V1A in mediating the neuroprotective effects of FK506 was validated by analyzing FK506 activity with respect to autophagy via acridine orange staining and transcription factor EB (TFEB) translocation assay. These analyses demonstrated that the binding of FK506 with ATP6V1A induces autophagy by activating the translocation of TFEB from the cytosol into the nucleus. Because autophagy has been identified as a mechanism for treating neurodegenerative diseases and because we have demonstrated that FK506 induces autophagy, this study demonstrates that FK506 is a possible new therapy for treating neurodegenerative diseases.
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| 10. |
- Kim, Tae Young, et al.
(author)
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Dna polymerase alpha subunit b is a binding protein for erlotinib resistance in non-small cell lung cancer
- 2020
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In: Cancers. - : MDPI AG. - 2072-6694. ; 12:9, s. 1-14
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Journal article (peer-reviewed)abstract
- Erlotinib inhibits epithelial growth factor receptor (EGFR) kinase activity and is used to treat non-small cell lung cancer (NSCLC). Despite its high efficacy, recurrence can occur in patients who become resistant to the drug. To address the underlying mechanism of Erlotinib resistance, we investigated additional mechanisms related to mode-of-drug-action, by multiple protein-binding interactions, besides EGFR by using drug affinity responsive target stability (DARTS) and liquid chromatography-mass spectrometry (LC-MS/MS) methods with non-labeled Erlotinib. DNA polymerase alpha subunit B (POLA2) was identified as a new Erlotinib binding protein that was validated by the DARTS platform, complemented with cellular thermal shift assays. Genetic knock-down of POLA2 promoted the anti-proliferative effect of the drug in the Erlotinib-resistant cell line H1299 with high POLA2 expression, whereas the overexpression of POLA2 restored anti-proliferative effects in the Erlotinib-sensitive cell line HCC827 with low POLA2 expression. Importantly, POLA2 expression levels in four NSCLC cell lines were positively correlated with anti-proliferative Erlotinib efficacy (Pearson correlation coefficient, R = 0.9886). These results suggest that POLA2 is a novel complementary target protein of Erlotinib, and could clinically provide validity as a surrogate marker for drug resistance in patients with NSCLC.
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