Publications by authors named "Nayoung Lee"

58 Publications

Sex Difference and Smoking Effect of Lung Cancer Incidence in Asian Population.

Cancers (Basel) 2020 Dec 31;13(1). Epub 2020 Dec 31.

Department of Pulmonary, Allergy and Critical Care Medicine, Hallym University Sacred Heart Hospital, Anyang 14068, Korea.

This study analyzed the sex difference in the effect of smoking exposure on lung cancer in terms of absolute and relative risks despite the increasing lung cancer incidence in Asian female never smokers. A retrospective cohort study was conducted on individuals aged 40-79 years who participated in the national health screening program in 2007 and 2008 with linkage to the Korea Central Cancer Registry records. We evaluated sex differences in the age-standardized incidence rate (ASR) of lung cancer by smoking history and the hazard ratio (HR) after adjusting for potential confounders. ASRs for male and female never smokers were 92.5 and 38.3 per 100,000 person-years, respectively (rate ratio (RR) = 2.4; 95% confidence interval (CI) = 2.3-2.5). ASRs for male and female current smokers with a 30 pack-year smoking history were 305.3 and 188.4 per 100,000 person-years, respectively (RR = 1.6; 95% CI = 1.3-2.0). Smoking was significantly associated with lung cancer risk for both sexes. HRs for former smokers versus never smokers were 1.27 (95% CI = 1.23-1.33) for men and 1.43 (95% CI = 1.16-1.81) for women. HRs for current smokers versus never smokers were 2.71 (95% CI = 2.63-2.79) for men and 2.70 (95% CI = 2.48-2.94) for women. HRs for lung cancer increased similarly in both men and women according to smoking status. However, among Korean individuals with comparable smoking statuses, lung cancer incidence is higher in men than in women. Sex should be considered in combination with smoking history in the selection of a lung cancer screening target population.
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http://dx.doi.org/10.3390/cancers13010113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7794680PMC
December 2020

Neuroprotective Effects of Baicalein, Wogonin, and Oroxylin A on Amyloid Beta-Induced Toxicity via NF-κB/MAPK Pathway Modulation.

Molecules 2020 Nov 2;25(21). Epub 2020 Nov 2.

Department of Food Science and Nutrition, Dong-A University, Busan 49315, Korea.

Amyloid beta (Aβ) peptide, one of the most important pathogenic traits of Alzheimer's disease (AD), invokes a cascade of oxidative damage and eventually leads to neuronal death. In the present study, baicalein, wogonin, and oroxylin A, main active flavones in , were evaluated for their neuroprotective effects against Aβ-stimulated damage. All tested compounds decreased Aβ-induced ROS generation and cell cycle arrest. In particular, baicalein exhibited the strongest antioxidant activity. In addition, these compounds suppressed apoptosis by attenuating mitochondrial dysfunction such as loss of membrane potential, Ca accumulation and Bax/Bcl-2 ratio. Furthermore, all tested flavones inhibited the expression of iNOS and COX-2, which resulted in suppressing inflammatory cytokines including TNF-α, NO, and PGE. Noticeably, all compounds exhibited the anti-inflammatory effects through downregulating NF-κB/MAPK pathway. Especially, oroxylin A was effective against both p65 and IκBα, while wogonin and baicalein were suppressed phospho-p65 and phospho-IκBα, respectively. Taken together, baicalein, wogonin, and oroxylin A can effectively relieve Aβ-stimulated neuronal apoptosis and inflammation in PC12 cells via downregulating NF-κB/MAPK signaling pathway.
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http://dx.doi.org/10.3390/molecules25215087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7662334PMC
November 2020

Discovery of Sulforaphane as a Potent BACE1 Inhibitor Based on Kinetics and Computational Studies.

Nutrients 2020 Oct 2;12(10). Epub 2020 Oct 2.

Department of Food Science and Nutrition, College of Health Sciences, Dong-A University, Busan 49315, Korea.

BACE1 is the rate-limiting enzyme involved in the production and deposition of β-amyloid (Aβ). Since neurotoxic Aβ plays a critical role in Alzheimer's disease (AD) pathogenesis, BACE1 has emerged as a key target for preventing AD. In the present study, the potential of sulforaphane, an isothiocyanate found in cruciferous vegetables, as a BACE1 inhibitor has been investigated. Sulforaphane exhibited six times more potent activity against BACE1 compared to well-known positive controls including resveratrol and quercetin. Sulforaphane presented selective and non-competitive BACE1 inhibitory activity with low off-target inhibition of BACE2 and other aspartic and serine proteases. In addition, sulforaphane presented negative binding energy, suggesting that the compound had a high affinity for BACE1. It interacted with locations other than the active binding sites of BACE1 through van der Waals forces. Overall, sulforaphane appeared to be a promising candidate with potent and selective BACE1 inhibitory properties that play an important role in AD prevention.
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http://dx.doi.org/10.3390/nu12103026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7601397PMC
October 2020

Utility of confocal microscopy in the management of lentigo maligna and lentigo maligna melanoma.

J Am Acad Dermatol 2020 Aug 29. Epub 2020 Aug 29.

The Ronald O. Perelman Department of Dermatology, NYU Grossman School of Medicine New York, New York 10016. Electronic address:

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http://dx.doi.org/10.1016/j.jaad.2020.08.101DOI Listing
August 2020

Chemical Controllable Gene Drive in .

ACS Synth Biol 2020 09 24;9(9):2362-2377. Epub 2020 Aug 24.

Department of Pharmacology, BK21 PLUS Project for Medical Science, Yonsei University College of Medicine, 50-1Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea.

Gene drive systems that propagate transgenes via super-Mendelian inheritance can potentially control insect-borne diseases and agricultural pests. However, concerns have been raised regarding unforeseen ecological consequences, and methods that prevent undesirable gene drive effects have been proposed. Here, we report a chemical-induced control of gene drive. We prepared a CRISPR-based gene drive system that can be removed by a site-specific recombinase, Rippase, the expression of which is induced by the chemical RU486 in fruit flies. Exposure of fruit flies to RU486 resulted in 7-12% removal of gene drive elements at each generation, leading to a significant reduction in gene drive-fly propagation. Mathematical modeling and simulation suggest that our system offers several advantages over a previously reported gene drive control system. Our chemical control system can provide a proof-of-principle for the reversible control of gene drive effects depending on ecological status and human needs.
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http://dx.doi.org/10.1021/acssynbio.0c00117DOI Listing
September 2020

Building customizable auto-luminescent luciferase-based reporters in plants.

Elife 2020 03 25;9. Epub 2020 Mar 25.

Department Genetics, Cell Biology, & Development, University of Minnesota, Minneapolis, United States.

Bioluminescence is a powerful biological signal that scientists have repurposed as a reporter for gene expression in plants and animals. However, there are downsides associated with the need to provide a substrate to these reporters, including its high cost and non-uniform tissue penetration. In this work we reconstitute a fungal bioluminescence pathway (FBP) using a composable toolbox of parts. We demonstrate that the FBP can create luminescence across various tissues in a broad range of plants without external substrate addition. We also show how our toolbox can be used to deploy the FBP to build auto-luminescent reporters for the study of gene-expression and hormone fluxes. A low-cost imaging platform for gene expression profiling is also described. These experiments lay the groundwork for future construction of programmable auto-luminescent plant traits, such as light driven plant-pollinator interactions or light emitting plant-based sensors.
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http://dx.doi.org/10.7554/eLife.52786DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7164954PMC
March 2020

Characterizing index keratinocytic carcinomas in commercially insured adults younger than age 50 years in the United States.

J Am Acad Dermatol 2020 Nov 8;83(5):1458-1460. Epub 2020 Mar 8.

The Ronald O. Perelman Department of Dermatology, New York University Grossman School of Medicine, New York. Electronic address:

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http://dx.doi.org/10.1016/j.jaad.2020.02.074DOI Listing
November 2020

A Split-Scar Study Investigating the Effectiveness of Early Intervention With Electroabrasion on Improving the Cosmetic Appearance of Postsurgical Scars.

Dermatol Surg 2020 10;46(10):1300-1305

Dermatology, Dermatologic and Mohs Micrographic Surgery, University of California San Diego, San Diego, California.

Background: Electroabrasion, which uses an in-office electrosurgical device, is a method of surgical planning that ablates the skin to the papillary dermis. Several reports demonstrate that intraoperative ablative interventions with lasers or dermabrasion can modulate scar formation more effectively. This investigation uses electroabrasion intraoperatively to mitigate scar formation.

Objective: To evaluate the effectiveness of intraoperative electroabrasion for scar revision.

Materials And Methods: This was a prospective, randomized, observer-blinded, split-scar study with 24 linear scar segments resulting from primary closures in patients undergoing Mohs micrographic surgery. After placement of dermal sutures, half of the wound was randomly treated with electroabrasion. The other half was used as the control. Scar appearance was assessed by a blinded observer and by the patient using the Patient and Observer Scar Assessment Scale at 1 to 2 weeks, 1 month, and 3 months after surgery.

Results: At the 3-month follow-up, both patient and observer variables measuring scar contour improved on the treated side, whereas erythema was worse. Overall, no difference was seen in total scores between the 2 sides.

Conclusion: Based on this pilot study, scars treated with electroabrasion revealed improved surface topography but worsened erythema. Future studies with more refined electrosurgical settings are needed for further evaluation.
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http://dx.doi.org/10.1097/DSS.0000000000002324DOI Listing
October 2020

ICT-Based Comprehensive Health and Social-Needs Assessment System for Supporting Person-Centered Community Care.

Healthc Inform Res 2019 Oct 31;25(4):338-343. Epub 2019 Oct 31.

Social Economy Institute, Daejeon, Korea.

Objectives: This study developed an information and communication technology (ICT)-based comprehensive health and social-needs assessment (CHSNA) system based on the International Classification of Functioning, Disability, and Health (ICF) with the aim of enhancing person-centered community care for community residents and supporting healthcare professionals and social workers who provide healthcare and social services in the community.

Methods: Items related to a CHSNA tool were developed and mapped with ICF codes. Experts validated the CHSNA system design and process using the Delphi method, and a pilot test of the initial version of the system was conducted.

Results: The following three steps of CHSNA were embedded in the system, which had a user-friendly screen and images: basic health assessment, life and activity assessment, and in-depth health assessment. The assessment results for the community residents were presented with visualized health profiles, including images, graphs, and an ICF model.

Conclusions: The developed CHSNA system can be used by healthcare professionals, social workers, and community residents to evaluate the reasoning underlying health and social needs, to facilitate the identification of more appropriate healthcare plans, and to guide community residents to receive the best healthcare services. A CHSNA system can improve the implementation of standardized terminology utilizing the ICF and the accuracy of needs assessments of community residents.
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http://dx.doi.org/10.4258/hir.2019.25.4.338DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6859262PMC
October 2019

Pilot Testing of an ICT-Based Care Management Support System to Deliver Integrated Community Care.

Stud Health Technol Inform 2019 Aug;264:1821-1822

College of Nursing, Chungnam, National University, Daejeon, Republic of Korea.

The purpose of this study was to develop an ICT-based care-management support system and to assess its validity and applicability through pilot testing. The system links users' health and social needs to community resources. Users and care managers participated in each step of care management through an interactive decision support system. The system contributes to facilitate person-centered community care.
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http://dx.doi.org/10.3233/SHTI190665DOI Listing
August 2019

Development of ICT-Based Comprehensive Health and Social-Needs Assessment System to Enhance Person-Centered Community Care.

Stud Health Technol Inform 2019 Aug;264:1694-1695

College of Nursing, Chungnam, National University, Daejeon, Republic of Korea.

We developed a comprehensive health and social-need assessment system to evaluate the diverse needs of elders with chronic illnesses in the community and to enhance the connection of their needs to health and social services. A comprehensive needs-assessment tool and profiles were integrated into the ICT system. We found that care managers could assess elders' needs comprehensively and connect those needs to suitable health and social services systematically.
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http://dx.doi.org/10.3233/SHTI190601DOI Listing
August 2019

Quantification of the Dynamic Phosphorylation Process of ERK Using Stable Isotope Dilution Selective Reaction Monitoring Mass Spectrometry.

Proteomics 2019 09 7;19(17):e1900086. Epub 2019 Aug 7.

Department of Applied Chemistry, Institute of Natural Science, Global Center for Pharmaceutical Ingredient Materials, Kyung Hee University, Yongin, 17104, Republic of Korea.

Mitogen-activated protein (MAP) kinase signaling is critical for various cellular responses, including cell proliferation, differentiation, and cell death. The MAP kinase cascade is conserved in the eukaryotic kingdom as a three-tiered kinase module-MAP kinase kinase kinase, MAP kinase kinase, and MAP kinase-that transduces signals via sequential phosphorylation upon stimulation. Dual phosphorylation of MAP kinase on the conserved threonine-glutamic acid-tyrosine (TEY) motif is essential for its catalytic activity and signal activation; however, the molecular mechanism by which the two residues are phosphorylated remains elusive. In the present study, the pattern of dual phosphorylation of extracellular signal-regulated kinase (ERK) is profiled on the TEY motif using stable isotope dilution (SID)-selective reaction monitoring (SRM) mass spectrometry (MS) to elucidate the order and magnitude of endogenous ERK phosphorylation in cellular model systems. The SID-SRM-MS analysis of phosphopeptides demonstrates that tyrosine phosphorylation in the TEY motif is dynamic, while threonine phosphorylation is static. Analyses of the mono-phosphorylatable mutants ERK and ERK indicate that phosphorylation of tyrosine is not affected by the phosphorylation state of threonine, while threonine phosphorylation depends on tyrosine phosphorylation. The data suggest that dual phosphorylation of ERK is a highly ordered and restricted mechanism determined by tyrosine phosphorylation.
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http://dx.doi.org/10.1002/pmic.201900086DOI Listing
September 2019

The genome of the giant Nomura's jellyfish sheds light on the early evolution of active predation.

BMC Biol 2019 03 29;17(1):28. Epub 2019 Mar 29.

Ecological Risk Research Division, Korea Institute of Ocean Science and Technology (KIOST), Geoje, 53201, Republic of Korea.

Background: Unique among cnidarians, jellyfish have remarkable morphological and biochemical innovations that allow them to actively hunt in the water column and were some of the first animals to become free-swimming. The class Scyphozoa, or true jellyfish, are characterized by a predominant medusa life-stage consisting of a bell and venomous tentacles used for hunting and defense, as well as using pulsed jet propulsion for mobility. Here, we present the genome of the giant Nomura's jellyfish (Nemopilema nomurai) to understand the genetic basis of these key innovations.

Results: We sequenced the genome and transcriptomes of the bell and tentacles of the giant Nomura's jellyfish as well as transcriptomes across tissues and developmental stages of the Sanderia malayensis jellyfish. Analyses of the Nemopilema and other cnidarian genomes revealed adaptations associated with swimming, marked by codon bias in muscle contraction and expansion of neurotransmitter genes, along with expanded Myosin type II family and venom domains, possibly contributing to jellyfish mobility and active predation. We also identified gene family expansions of Wnt and posterior Hox genes and discovered the important role of retinoic acid signaling in this ancient lineage of metazoans, which together may be related to the unique jellyfish body plan (medusa formation).

Conclusions: Taken together, the Nemopilema jellyfish genome and transcriptomes genetically confirm their unique morphological and physiological traits, which may have contributed to the success of jellyfish as early multi-cellular predators.
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http://dx.doi.org/10.1186/s12915-019-0643-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6441219PMC
March 2019

The Draft Genome of an Octocoral, Dendronephthya gigantea.

Genome Biol Evol 2019 03;11(3):949-953

Ecological Risk Research Division, Korea Institute of Ocean Science and Technology (KIOST), Geoje, Republic of Korea.

Coral reefs composed of stony corals are threatened by global marine environmental changes. However, soft coral communities of octocorallian species, appear more resilient. The genomes of several cnidarians species have been published, including from stony corals, sea anemones, and hydra. To fill the phylogenetic gap for octocoral species of cnidarians, we sequenced the octocoral, Dendronephthya gigantea, a nonsymbiotic soft coral, commonly known as the carnation coral. The D. gigantea genome size is ∼276 Mb. A high-quality genome assembly was constructed from PacBio long reads (29.85 Gb with 108× coverage) and Illumina short paired-end reads (35.54 Gb with 128× coverage) resulting in the highest N50 value (1.4 Mb) reported thus far among cnidarian genomes. About 12% of the genome is repetitive elements and contained 28,879 predicted protein-coding genes. This gene set is composed of 94% complete BUSCO ortholog benchmark genes, which is the second highest value among the cnidarians, indicating high quality. Based on molecular phylogenetic analysis, octocoral and hexacoral divergence times were estimated at 544 MYA. There is a clear difference in Hox gene composition between these species: unlike hexacorals, the Antp superclass Evx gene was absent in D. gigantea. Here, we present the first genome assembly of a nonsymbiotic octocoral, D. gigantea to aid in the comparative genomic analysis of cnidarians, including stony and soft corals, both symbiotic and nonsymbiotic. The D. gigantea genome may also provide clues to mechanisms of differential coping between the soft and stony corals in response to scenarios of global warming.
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http://dx.doi.org/10.1093/gbe/evz043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6447388PMC
March 2019

Doxorubicin-induced heart failure in cancer patients: A cohort study based on the Korean National Health Insurance Database.

Cancer Med 2018 12 19;7(12):6084-6092. Epub 2018 Nov 19.

Department of Cardiology, Center for Clinical Specialty, National Cancer Center, Goyang-si, Korea.

Background: Doxorubicin is a typical anticancer drug that causes cardiomyopathy and heart failure (HF). The aim of our study was to investigate incidence, risk factors for doxorubicin-induced HF in Korean cancer patients and their survival rate, utilizing a nationwide population-based cohort.

Methods: We analyzed 58 541 cancer patients who received doxorubicin between 2003 and 2010. Descriptive analysis was performed in patients with breast cancer, hematologic malignancy, gynecological malignancy, and sarcoma. Risk factors associated with doxorubicin-induced HF were investigated using a Cox proportional hazards model. The survival rate of doxorubicin-induced HF patients was compared with that of patients without doxorubicin-induced HF.

Results: A total of 2324 (4%) were diagnosed with doxorubicin-induced HF. In patients with breast cancer, predictive risk factors for doxorubicin-induced HF included age over 65 years [hazard ratio (HR) 1.34, 95% confidence interval (CI) 1.05-1.72], hypertension [HR 2.45 (2.12- 2.84)], diabetes mellitus [HR 1.26 (1.05-1.51)], coronary artery disease [HR 2.08 (1.63-2.66)], advanced stage [HR 1.31 (1.13-1.50)], and trastuzumab administration [HR 2.94 (2.54-3.40)]. In patients with hematologic malignancy, predictive risk factors included age over 65 years [HR 1.75 (1.49-2.07)], hypertension [HR 1.62 (1.37-1.92)], and coronary artery disease [HR 2.28 (1.80-2.89)]. Five-year survival rates of patients with doxorubicin-induced HF were significantly lower relative to those of patients without HF in breast cancer and hematologic malignancy: 80% vs 84% and 69% vs 75%, respectively (P < 0.001).

Conclusions: In cancer patients treated with doxorubicin, management of risk factors, early detection, and treatment for doxorubicin-induced HF might be critical for patient survival.
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http://dx.doi.org/10.1002/cam4.1886DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6308087PMC
December 2018

Increased Prevalence of Thalassemia in Young People in Korea: Impact of Increasing Immigration.

Ann Lab Med 2019 Mar;39(2):133-140

Department of Laboratory Medicine, Seoul National University Hospital, Seoul, Korea.

Background: Thalassemia is highly prevalent in Southeast Asia but is rare in Korea; however, Southeast Asian immigrant population is recently rising in Korea. We investigated the prevalence of thalassemia in Korea in the context of increasing immigration.

Methods: This prospective, observational, multicenter study was conducted between September 2015 and August 2017. A total of 669 subjects <30 years living in Korea were grouped into the multiethnic (N=314) and Korean (N=355) groups. Hb electrophoresis and complete blood count (CBC) were performed. If low mean corpuscular volume with high red blood cell distribution width coefficient of variation or a high fetal Hb (HbF) or Hb alpha 2 (HbA₂) level was observed, genetic testing of the α- and β-globin genes was performed. In addition, the number of potential thalassemia carriers in Korea was estimated by multiplying the prevalence of thalassemia in a specific ethnicity by the number of immigrants of that ethnicity.

Results: Twenty-six multiethnic and 10 Korean subjects showed abnormal results for Hb electrophoresis and CBC. Eighteen multiethnic subjects and four Korean subjects were tested for α-globin and β-globin gene mutations. Within the multiethnic group, five subjects (1.5%) were α-thalassemia carriers, and six (1.9%) were β-thalassemia minor. The deletion in and , and c. 126_129delCTTT (p.Phe42Leufs*19) mutation of were the dominant inherited mutations.

Conclusions: The prevalence of thalassemia in young people in Korea is increasing due to the increasing number of Southeast Asian immigrants.
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http://dx.doi.org/10.3343/alm.2019.39.2.133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6240526PMC
March 2019

Evaluation of similar quality attribute characteristics in SB5 and reference product of adalimumab.

MAbs 2019 01 19;11(1):129-144. Epub 2018 Oct 19.

b Bioanalysis Team , Samsung Bioepis Co., Ltd ., Incheon , South Korea.

Biosimilars are biologic products that are highly similar to a licensed reference product in terms of quality, safety, and efficacy. SB5 is a biosimilar of Humira® (adalimumab) developed by Samsung Bioepis. To demonstrate its biosimilarity in quality to Humira®, we performed a comprehensive characterization in terms of structure, physicochemical properties, and biological properties following the International Conference on Harmonization, US Food and Drug Administration, and European Medicines Agency guidelines. We analyzed all available batches of SB5 and more than 100 EU- and US-sourced lots of Humira® using state-of-the-art methods whenever possible, and compared the two sets of data. The structural properties comprised primary and higher-order structures and N-glycosylation. The physicochemical characteristics were categorized into liquid chromatographic patterns and electrophoretic pattern concerning size and charge heterogeneity. The biological properties were examined by in vitro functional assays. Overall, SB5 and Humira® were shown to be similar to each other in terms of quality attributes. For some of the quality attributes, minor differences were observed. However, the observed differences have been adequately addressed and demonstrated these do not translate into clinically meaningful differences in terms of safety, purity, and potency.
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http://dx.doi.org/10.1080/19420862.2018.1530920DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6343792PMC
January 2019

Molecular basis of flowering under natural long-day conditions in Arabidopsis.

Nat Plants 2018 10 24;4(10):824-835. Epub 2018 Sep 24.

Department of Biology, University of Washington, Seattle, WA, USA.

Plants sense light and temperature changes to regulate flowering time. Here, we show that expression of the Arabidopsis florigen gene, FLOWERING LOCUS T (FT), peaks in the morning during spring, a different pattern than we observe in the laboratory. Providing our laboratory growth conditions with a red/far-red light ratio similar to open-field conditions and daily temperature oscillation is sufficient to mimic the FT expression and flowering time in natural long days. Under the adjusted growth conditions, key light signalling components, such as phytochrome A and EARLY FLOWERING 3, play important roles in morning FT expression. These conditions stabilize CONSTANS protein, a major FT activator, in the morning, which is probably a critical mechanism for photoperiodic flowering in nature. Refining the parameters of our standard growth conditions to more precisely mimic plant responses in nature can provide a powerful method for improving our understanding of seasonal response.
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http://dx.doi.org/10.1038/s41477-018-0253-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6195122PMC
October 2018

Uncoupling FT Protein Transport from its Function.

Plant Cell Physiol 2018 08;59(8):1487-1489

Department of Biology, University of Washington, Seattle, WA, USA.

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http://dx.doi.org/10.1093/pcp/pcy123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6454791PMC
August 2018

Time-Lapse Live-Cell Imaging Reveals Dual Function of Oseg4, WDR35, in Ciliary Protein Trafficking.

Mol Cells 2018 Jul 9;41(7):676-683. Epub 2018 Jul 9.

Department of Oral Biology, BK21 PLUS, Yonsei University College of Dentistry, Seoul 03722, Korea.

Cilia are highly specialized antennae-like organelles that extend from the cell surface and act as cell signaling hubs. Intraflagellar transport (IFT) is a specialized form of intracellular protein trafficking that is required for the assembly and maintenance of cilia. Because cilia are so important, mutations in several IFT components lead to human disease. Thus, clarifying the molecular functions of the IFT proteins is a high priority in cilia biology. Live imaging in various species and cellular preparations has proven to be an important technique in both the discovery of IFT and the mechanisms by which it functions. Live imaging of cilia, however, has not yet been reported. Here, we have visualized the movement of IFT in cilia using time-lapse live imaging for the first time. We found that NOMPB-GFP (IFT88) moves according to distinct parameters depending on the ciliary segment. NOMPB-GFP moves at a similar speed in proximal and distal cilia toward the tip (~0.45 μm/s). As it returns to the ciliary base, however, NOMPB-GFP moves at ~0.12 μm/s in distal cilia, accelerating to ~0.70 μm/s in proximal cilia. Furthermore, while live imaging NOMPB-GFP, we observed one of the IFT proteins required for retrograde movement, Oseg4 (WDR35), is also required for anterograde movement in distal cilia. We anticipate our time-lapse live imaging analysis technique in cilia will be a good starting point for a more sophisticated analysis of IFT and its molecular mechanisms.
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http://dx.doi.org/10.14348/molcells.2018.0179DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6078859PMC
July 2018

Incorporation of Si and Zr into Pure HfO₂ and Its Effects on Dielectric Integrity.

J Nanosci Nanotechnol 2018 09;18(9):5899-5903

College of Information and Communication Engineering, Sungkyunkwan University, Suwon 16419, Republic of Korea.

Hafnium-silicate (HfSiO4, (HfO2)x(SiO2)1-x) and hafnium-zirconate (HfZrO4, (HfO2)x(ZrO2)1-x) films were employed as a gate dielectric to enhance the electrical properties of pure HfO2. (HfO2)x(SiO2)1-x and (HfO2)x(ZrO2)1-x films were formed onto p-Si substrates with varying degrees of Hf content x (x = 1, 0.9, 0.7, and 0.5) via solution processing. With regard to (HfO2)x(SiO2)1-x, the leakage current decreased from 1.94 × 10-8 to 4.29 × 10-9 A/cm2 at a gate voltage of VG = -1 V when the HfO2 content was reduced. These resulted from the reduction of leakage paths through the interface between HfSiO4 and Si substrate. Additionally, (HfO2)x(ZrO2)1-x exhibited the lowest interfacial trap density of 3.4 × 1011 cm-2 eV-1 for x = 0.5 due to a reduction in root mean square (RMS) roughness of the film from 6.0 to 4.2 nm. From the results, it was found that (HfO2)0.5(SiO2)0.5 demonstrated excellent oxide integrity in contact with Si substrates, whereas (HfO2)0.5(ZrO2)0.5 demonstrated an enhanced film morphology and maintained a high dielectric constant value. Finally, the HfZrO4/HfSiO4/Si structure revealed a gate oxide with enhanced integrity compared to pure HfO2-based devices.
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http://dx.doi.org/10.1166/jnn.2018.15584DOI Listing
September 2018

The FBH family of bHLH transcription factors controls ACC synthase expression in sugarcane.

J Exp Bot 2018 04;69(10):2511-2525

Departamento de Genética, Evolução, Microbiologia e Imunologia, Instituto de Biologia, Universidade Estadual de Campinas, CP, Campinas, SP, Brazil.

Ethylene is a phytohormone involved in the regulation of several aspects of plant development and in responses to biotic and abiotic stress. The effects of exogenous application of ethylene to sugarcane plants are well characterized as growth inhibition of immature internodes and stimulation of sucrose accumulation. However, the molecular network underlying the control of ethylene biosynthesis in sugarcane remains largely unknown. The chemical reaction catalyzed by 1-aminocyclopropane-1-carboxylic acid synthase (ACS) is an important rate-limiting step that regulates ethylene production in plants. In this work, using a yeast one-hybrid approach, we identified three basic helix-loop-helix (bHLH) transcription factors, homologs of Arabidopsis FBH (FLOWERING BHLH), that bind to the promoter of ScACS2 (Sugarcane ACS2), a sugarcane type 3 ACS isozyme gene. Protein-protein interaction assays showed that sugarcane FBH1 (ScFBH1), ScFBH2, and ScFBH3 form homo- and heterodimers in the nucleus. Gene expression analysis revealed that ScFBHs and ScACS2 transcripts are more abundant in maturing internodes during afternoon and night. In addition, Arabidopsis functional analysis demonstrated that FBH controls ethylene production by regulating transcript levels of ACS7, a homolog of ScACS2. These results indicate that ScFBHs transcriptionally regulate ethylene biosynthesis in maturing internodes of sugarcane.
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http://dx.doi.org/10.1093/jxb/ery083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5920332PMC
April 2018

Benchmarking Implications: Analysis of Medicare Accountable Care Organizations Spending Level and Quality of Care.

J Healthc Qual 2018 Nov/Dec;40(6):344-353

Early evidence has shown that Accountable Care Organizations (ACOs) have achieved some success in improving the quality of care and reducing Medicare costs. However, it has been argued that the ACO rewarding model may disproportionately affect relatively low-spending (LS; considered as efficient) organizations that have fewer options to cut unnecessary services compared with high-spending (HS; inefficient) organizations. We conducted a cross-sectional retrospective study to compare ACO financial and quality of care performance between HS-ACO and LS-ACO. After adjusting for ACO organizational factors and beneficiary characteristics, we found that HS-ACOs generated greater savings per beneficiary than LS-ACOs ($501 vs. -$108, p < .001); however, HS-ACOs had a lower quality of care performance (48.79 vs. 53.29, p = .002). Specifically, LS-ACOs had better quality performance than HS-ACOs in patient experience/satisfaction (p = .02), preventive care services (p = .004), and hospitalization management (p = .001), whereas HS-ACOs better performed in routine checkup/follow-up (p < .001) and risk population management (p = .048). Our findings indicated that Medicare ACO rewarding model seems to be advantageous for HS-ACOs regardless of the overall quality of care performance.
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http://dx.doi.org/10.1097/JHQ.0000000000000123DOI Listing
September 2019

Assessing Skin Cancer Using Epidermal Genetic Information Retrieved by Adhesive Patch Skin Surface Sampling.

Dermatol Clin 2017 Oct 7;35(4):521-524. Epub 2017 Aug 7.

Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, 1600 NW 10th Avenue, Miami, FL 33136, USA; Private Practice, Skin and Cancer Associates, Plantation, FL 33324, USA. Electronic address:

The detection of melanoma can be challenging. Many patients have clinically equivocal lesions in cosmetically sensitive areas or have multiple suspicious lesions. Epidermal genetic information retrieval is a noninvasive diagnostic method involving the application of adhesive tape onto the skin's surface to recover genomic material from the epidermis. This genomic material can then be used in assays to determine gene expression profiles. Studies have shown the potential of this technology to aid clinicians in differentiating between melanomas and nevi. Although this technology is not meant to replace a biopsy, it can help guide the decision whether to biopsy.
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http://dx.doi.org/10.1016/j.det.2017.06.013DOI Listing
October 2017

Confocal microscopy in the diagnosis of fibreglass dermatitis.

Contact Dermatitis 2017 Oct;77(4):266-267

Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL, 33136, USA.

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http://dx.doi.org/10.1111/cod.12818DOI Listing
October 2017

IgA multiple myeloma in a patient with an IgG pemphigus foliaceus-like exanthem.

Int J Dermatol 2017 Oct 30;56(10):1058-1060. Epub 2017 Aug 30.

Department of Dermatology, Harvard Medical School, Boston, MA, USA.

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http://dx.doi.org/10.1111/ijd.13721DOI Listing
October 2017

Plant array chip for the germination and growth screening of Arabidopsis thaliana.

Lab Chip 2017 09;17(18):3071-3077

Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), 291 Daehak-ro, Yuseong-gu, Daejeon 34141, Republic of Korea.

A screening process for the germination and growth of seed is generally required for plant research. Such a repetitive screening process is costly and time-consuming, and its bulky setup requires a lot of space. In particular, the control of the variables, such as light, nutrients, hormones and temperature, is difficult due to the limited space for incubation. In addition, small seeds such as Arabidopsis thaliana are difficult to handle as they are hundreds of microns in diameter and require a more precisely controllable screening environment. However, conventional screening methods involve the seeding of multiple seeds on a single agarose plate without physical partitions. Such methods need to be improved because they lack control over the growth environment and the results are highly dependent on the researchers. To overcome the above-mentioned limitations, a novel seeding array chip has been developed which can be filled with conventional solid agarose while enabling more efficient screening. Individual seeds can be partitioned from each other and a number of different agarose conditions can be tested in a single plant array chip. As a demonstration, we tested the effect of various concentrations of Murashige and Skoog medium and a plant hormone (e.g., abscisic acid) on the growth of Arabidopsis. The chip can efficiently save the space required for screening by providing different conditions for ∼400 seeds in a 59 × 55 mm chip, and it also provides easy observation and analysis of seed growth. The proposed plant array chip is expected to contribute to more efficient screening of essential phenotypes such as germination and growth for both academic and industrial purposes.
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http://dx.doi.org/10.1039/c7lc00463jDOI Listing
September 2017

The Neuroprotective Marine Compound Psammaplysene A Binds the RNA-Binding Protein HNRNPK.

Mar Drugs 2017 Aug 7;15(8). Epub 2017 Aug 7.

Department of Pediatrics, Division of Neurology, Research Institute, Children's Hospital of Philadelphia, Room 814, 3615 Civic Center Boulevard, Philadelphia, PA 19104, USA.

In previous work, we characterized the strong neuroprotective properties of the marine compound Psammaplysene A (PA) in in vitro and in vivo models of neurodegeneration. Based on its strong neuroprotective activity, the current work attempts to identify the physical target of PA to gain mechanistic insight into its molecular action. Two distinct methods, used in parallel, to purify protein-binding partners of PA led to the identification of HNRNPK as a direct target of PA. Based on surface plasmon resonance, we find that the binding of PA to HNRNPK is RNA-dependent. These findings suggest a role for HNRNPK-dependent processes in neurodegeneration/neuroprotection, and warrant further study of HNRNPK in this context.
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http://dx.doi.org/10.3390/md15080246DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5577601PMC
August 2017

Physicochemical and biological characterization of SB2, a biosimilar of Remicade® (infliximab).

MAbs 2017 Feb/Mar;9(2):364-382. Epub 2016 Dec 22.

c Department of Medical Affairs , Biosimilars , Biogen , Zug , Switzerland.

A biosimilar is a biological medicinal product that contains a version of the active substance of an already authorized original biological medicinal product. Biosimilarity to the reference product (RP) in terms of quality characteristics, such as physicochemical and biological properties, safety, and efficacy, based on a comprehensive comparability exercise needs to be established. SB2 (Flixabi® and Renflexis®) is a biosimilar to Remicade® (infliximab). The development of SB2 was performed in accordance with relevant guidelines of the International Conference on Harmonisation, the European Medicines Agency, and the United States Food and Drug Administration. To determine whether critical quality attributes meet quality standards, an extensive characterization test was performed with more than 80 lots of EU- and US-sourced RP. The physicochemical characterization study results revealed that SB2 was similar to the RP. Although a few differences in physicochemical attributes were observed, the evidence from the related literature, structure-activity relationship studies, and comparative biological assays showed that these differences were unlikely to be clinically meaningful. The biological characterization results showed that SB2 was similar to the RP in terms of tumor necrosis factor-α (TNF-α) binding and TNF-α neutralization activities as a main mode of action. SB2 was also similar in Fc-related biological activities including antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity, neonatal Fc receptor binding, C1q binding, and Fc gamma receptor binding activities. These analytical findings support that SB2 is similar to the RP and also provide confidence of biosimilarity in terms of clinical safety and efficacy.
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http://dx.doi.org/10.1080/19420862.2016.1264550DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5297515PMC
November 2017