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Article ; Online: Human Cardiac Fibroblast Number and Activation State Modulate Electromechanical Function of hiPSC-Cardiomyocytes in Engineered Myocardium

Cassady E. Rupert / Tae Yun Kim / Bum-Rak Choi / Kareen L. K. Coulombe

Stem Cells International, Vol

2020 Volume 2020

Abstract: Cardiac tissue engineering using hiPSC-derived cardiomyocytes is a promising avenue for cardiovascular regeneration, pharmaceutical drug development, cardiotoxicity evaluation, and disease modeling. Limitations to these applications still exist due in ... ...

Abstract	Cardiac tissue engineering using hiPSC-derived cardiomyocytes is a promising avenue for cardiovascular regeneration, pharmaceutical drug development, cardiotoxicity evaluation, and disease modeling. Limitations to these applications still exist due in part to the need for more robust structural support, organization, and electromechanical function of engineered cardiac tissues. It is well accepted that heterotypic cellular interactions impact the phenotype of cardiomyocytes. The current study evaluates the functional effects of coculturing adult human cardiac fibroblasts (hCFs) in 3D engineered tissues on excitation and contraction with the goal of recapitulating healthy, nonarrhythmogenic myocardium in vitro. A small population (5% of total cell number) of hCFs in tissues improves tissue formation, material properties, and contractile function. However, two perturbations to the hCF population create disease-like phenotypes in engineered cardiac tissues. First, increasing the percentage of hCFs to 15% resulted in tissues with increased ectopic activity and spontaneous excitation rate. Second, hCFs undergo myofibroblast activation in traditional two-dimensional culture, and this altered phenotype ablated the functional benefits of hCFs when incorporated into engineered cardiac tissues. Taken together, the results of this study demonstrate that human cardiac fibroblast number and activation state modulate electromechanical function of hiPSC-cardiomyocytes and that a low percentage of quiescent hCFs are a valuable cell source to advance a healthy electromechanical response of engineered cardiac tissue for regenerative medicine applications.
Keywords	Internal medicine ; RC31-1245
Subject code	610
Language	English
Publishing date	2020-01-01T00:00:00Z
Publisher	Hindawi Limited
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Geographical Distribution of B orrelia burgdorferi sensu lato in Ticks Collected from Wild Rodents in the Republic of Korea

Seong Yoon Kim / Tae-Kyu Kim / Tae Yun Kim / Hee Il Lee

Pathogens, Vol 9, Iss 866, p

2020 Volume 866

Abstract: Lyme disease is a tick-borne zoonotic disease caused by Borrelia burgdorferi sensu lato (s. l.) via transmission cycles involving competent tick vectors and vertebrate reservoirs. Here, we determined the prevalence and distribution of Borrelia ... ...

Abstract	: Lyme disease is a tick-borne zoonotic disease caused by Borrelia burgdorferi sensu lato (s. l.) via transmission cycles involving competent tick vectors and vertebrate reservoirs. Here, we determined the prevalence and distribution of Borrelia genospecies in 738 ticks of at least three species from wild rodents in nine regions of the Republic of Korea (ROK). Ticks were analyzed using nested PCR targeting partial flagellin B gene sequences, followed by sequence analysis. The prevalence of B orrelia infection was 33.6%, and the most common genospecies were B. afzelii (62.5%), B. valaisiana (31.9%), B. yangtzensis (2.4%), B. garinii (1.6%), and B. tanukii (1.6%). Borrelia afzelii was found in all regions except Jeju Island; this predominant genospecies was found in the northern and central sampling regions . Borrelia valaisiana , B. yangtzensis , and B. tanukii were found only in the southern regions with B. valaisiana being the most common, whereas B. yangtzensis and B. tanukii were only found on Jeju Island. Our study is the first to describe the nationwide prevalence of B. burgdorferi s. l. in ticks from wild rodents in the ROK. Continuous surveillance in ticks, animals, humans, and different regions is required to avoid disease distribution and possible transmission to humans in the ROK.
Keywords	lyme disease ; Borrelia burgdorferi sensu lato ; tick ; wild rodent ; Medicine ; R
Subject code	630
Language	English
Publishing date	2020-10-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Action potential metrics and automated data analysis pipeline for cardiotoxicity testing using optically mapped hiPSC-derived 3D cardiac microtissues.

Arvin H Soepriatna / Allison Navarrete-Welton / Tae Yun Kim / Mark C Daley / Peter Bronk / Celinda M Kofron / Ulrike Mende / Kareen L K Coulombe / Bum-Rak Choi

PLoS ONE, Vol 18, Iss 2, p e

2023 Volume 0280406

Abstract: Recent advances in human induced pluripotent stem cell (hiPSC)-derived cardiac microtissues provide a unique opportunity for cardiotoxic assessment of pharmaceutical and environmental compounds. Here, we developed a series of automated data processing ... ...

Abstract	Recent advances in human induced pluripotent stem cell (hiPSC)-derived cardiac microtissues provide a unique opportunity for cardiotoxic assessment of pharmaceutical and environmental compounds. Here, we developed a series of automated data processing algorithms to assess changes in action potential (AP) properties for cardiotoxicity testing in 3D engineered cardiac microtissues generated from hiPSC-derived cardiomyocytes (hiPSC-CMs). Purified hiPSC-CMs were mixed with 5-25% human cardiac fibroblasts (hCFs) under scaffold-free conditions and allowed to self-assemble into 3D spherical microtissues in 35-microwell agarose gels. Optical mapping was performed to quantify electrophysiological changes. To increase throughput, AP traces from 4x4 cardiac microtissues were simultaneously acquired with a voltage sensitive dye and a CMOS camera. Individual microtissues showing APs were identified using automated thresholding after Fourier transforming traces. An asymmetric least squares method was used to correct non-uniform background and baseline drift, and the fluorescence was normalized (ΔF/F0). Bilateral filtering was applied to preserve the sharpness of the AP upstroke. AP shape changes under selective ion channel block were characterized using AP metrics including stimulation delay, rise time of AP upstroke, APD30, APD50, APD80, APDmxr (maximum rate change of repolarization), and AP triangulation (APDtri = APDmxr-APD50). We also characterized changes in AP metrics under various ion channel block conditions with multi-class logistic regression and feature extraction using principal component analysis of human AP computer simulations. Simulation results were validated experimentally with selective pharmacological ion channel blockers. In conclusion, this simple and robust automated data analysis pipeline for evaluating key AP metrics provides an excellent in vitro cardiotoxicity testing platform for a wide range of environmental and pharmaceutical compounds.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2023-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Site selection for offshore wind farms in the southwest coast of South Korea

Kim, Choong-Ki / Seonju Jang / Tae Yun Kim

Renewable energy. 2018 May, v. 120

2018

Abstract: This study is to provide guidance for selecting sites suitable for offshore wind farm developments with lower social, economic, and environmental impacts in the South Korea southwest coastal area with its complicated shoreline configuration, large ... ...

Abstract	This study is to provide guidance for selecting sites suitable for offshore wind farm developments with lower social, economic, and environmental impacts in the South Korea southwest coastal area with its complicated shoreline configuration, large ecologically important tidal flats, and various marine-based human activities. To analyze the economic feasibility of offshore wind farms, harvestable energy was calculated using an InVEST (Integrated Valuation of Environmental Services and Tradeoffs) model that has been used widely for marine ecosystem service analysis. Capital costs for grid connection and electricity transmission, operation and maintenance costs, and other costs were integrated together to calculate a net present value (NPV) of a 60-MW offshore wind farm assuming a lifetime of 20 years of operation. It is important to note that NPVs of offshore wind farms are affected significantly by the proximity to the closest inland substations, showing the importance of grid connection. Criteria that may cause social and environmental conflicts were grouped into three categories: nature conservation and landscape protection, marine-based human activities, and marine environment and marine ecosystem. Available datasets for each category were compiled and incorporated into GIS-based maps. Many social and environmental criteria overlapped spatially, and areas influenced by one or more criteria were designated as areas of potential conflicts. Economic analysis results and potential social and environmental conflicts were considered together to select areas that could produce wind energy more efficiently with minimum social and environmental conflicts. Economic, social, and environmental assessment strategies and procedures provided in this study can be used as an effective decision-making support tool to find sites for offshore wind farm development and various other offshore developments as well.
Keywords	capital ; coasts ; data collection ; decision making ; economic feasibility ; ecosystem services ; electricity ; energy ; environmental assessment ; environmental impact ; geographic information systems ; humans ; landscape management ; marine ecosystems ; marine environment ; models ; natural resources conservation ; shorelines ; wind farms ; wind power ; South Korea
Language	English
Dates of publication	2018-05
Size	p. 151-162.
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	2001449-1
ISSN	0960-1481
ISSN	0960-1481
DOI	10.1016/j.renene.2017.12.081
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Application of ferroelectric materials for improving output power of energy harvesters

Tae Yun Kim / Sung Kyun Kim / Sang-Woo Kim

Nano Convergence, Vol 5, Iss 1, Pp 1-

2018 Volume 16

Abstract: Abstract In terms of advances in technology, especially electronic devices for human use, there are needs for miniaturization, low power, and flexibility. However, there are problems that can be caused by these changes in terms of battery life and size. ... ...

Abstract	Abstract In terms of advances in technology, especially electronic devices for human use, there are needs for miniaturization, low power, and flexibility. However, there are problems that can be caused by these changes in terms of battery life and size. In order to compensate for these problems, research on energy harvesting using environmental energy (mechanical energy, thermal energy, solar energy etc.) has attracted attention. Ferroelectric materials which have switchable dipole moment are promising for energy harvesting fields because of its special properties such as strong dipole moment, piezoelectricity, pyroelectricity. The strong dipole moment in ferroelectric materials can increase internal potential and output power of energy harvesters. In this review, we will provide an overview of the recent research on various energy harvesting fields using ferroelectrics. A brief introduction to energy harvesting and the properties of the ferroelectric material are described, and applications to energy harvesters to improve output power are described as well.
Keywords	Ferroelectricity ; Energy harvesting ; Piezoelectricity ; Triboelectric effect ; Photovoltaic effect ; Technology ; T ; Chemical technology ; TP1-1185 ; Biotechnology ; TP248.13-248.65 ; Science ; Q ; Physics ; QC1-999
Subject code	690
Language	English
Publishing date	2018-11-01T00:00:00Z
Publisher	SpringerOpen
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Molecular evidence of zoonotic Babesia species, other than B. microti, in ixodid ticks collected from small mammals in the Republic of Korea

Tae Yun Kim / Seong Yoon Kim / Tae‐Kyu Kim / Hee IL Lee / Shin‐Hyeong Cho / Wook‐Gyo Lee / Hyunwoo Kim

Veterinary Medicine and Science, Vol 7, Iss 6, Pp 2427-

2021 Volume 2433

Abstract: Abstract The occurrence of tick‐borne infectious diseases, including zoonotic babesiosis, has become a serious concern in recent years. In this study, we detected Babesia spp. using polymerase chain reaction (PCR) amplification of the 18S rRNA of the ... ...

Abstract	Abstract The occurrence of tick‐borne infectious diseases, including zoonotic babesiosis, has become a serious concern in recent years. In this study, we detected Babesia spp. using polymerase chain reaction (PCR) amplification of the 18S rRNA of the parasites isolated from ixodid ticks collected from small mammals in the Republic of Korea (ROK). Sequence analysis of the PCR amplicon revealed the presence of B. duncani, B. venatorum, B. capreoli/divergens, and, the most prevalent, B. microti in the ticks. The molecular phylogenetic analysis showed that the four species‐specific18S rRNA sequences clustered in four distinct clades. This is the first study to provide molecular evidence for the presence of zoonotic Babesia spp. other than B. microti in ticks in the ROK.
Keywords	babesiosis ; Ixodidae ; ribosomal RNA ; the Republic of Korea ; tick ; Veterinary medicine ; SF600-1100
Language	English
Publishing date	2021-11-01T00:00:00Z
Publisher	Wiley
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: First Identification and Genotyping of Enterocytozoon bieneusi and Prevalence of Encephalitozoon intestinalis in Patients with Acute Diarrhea in the Republic of Korea

Ji-Young Kwon / Ji-Ye Seo / Tae-Yun Kim / Hee-Il Lee / Jung-Won Ju

Pathogens, Vol 10, Iss 1424, p

2021 Volume 1424

Abstract: Encephalitozoon intestinalis and Enterocytozoon bieneusi can cause diarrhea in humans, especially severe diarrhea in immunocompromised patients. However, there have been few studies on Enc. intestinalis and Ent. bieneusi in patients with acute diarrhea ... ...

Abstract	Encephalitozoon intestinalis and Enterocytozoon bieneusi can cause diarrhea in humans, especially severe diarrhea in immunocompromised patients. However, there have been few studies on Enc. intestinalis and Ent. bieneusi in patients with acute diarrhea in the Republic of Korea (ROK). In this study, fecal samples were collected from 1241 patients with acute diarrhea in 2020. Among these, 24 cases of Enc. intestinalis and one case of Ent. bieneusi were detected via PCR amplification of small subunit ribosomal RNA. Genotyping of the internal transcribed spacer region sequence revealed that the detected Ent. bieneusi genotype was in Group 1. This study provides the first evidence that Ent. bieneusi exists in humans in addition to animals in the ROK. To identify the causative agent, continuous monitoring of Enc. intestinalis and Ent. bieneusi is necessary for patients with acute diarrhea in the ROK.
Keywords	Encephalitozoon intestinalis ; Enterocytozoon bieneusi ; patient ; genotype ; phylogeny ; microsporidia ; Medicine ; R
Subject code	610
Language	English
Publishing date	2021-11-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Comparison of acute phase reactant levels of Kawasaki disease patients who visited with less than 5 days duration of fever and with 5 days or longer

Hyun Jeong Do / Jin Hee Jeong / Dong Hoon Kim / Tae Yun Kim / Changwoo Kang / Soo Hoon Lee / Sang Bong Lee

Pediatric Emergency Medicine Journal, Vol 6, Iss 1, Pp 11-

2019 Volume 16

Abstract: Purpose Kawasaki disease (KD) is a common, acute systemic vasculitis in children. Acute phase reactants (APRs) have been used to assist diagnosis, and to predict outcome in children with KD. However, it remains unknown on levels of APRs depending on ... ...

Abstract	Purpose Kawasaki disease (KD) is a common, acute systemic vasculitis in children. Acute phase reactants (APRs) have been used to assist diagnosis, and to predict outcome in children with KD. However, it remains unknown on levels of APRs depending on duration of fever. We aimed to compare APR levels of children with KD who visited with < 5 days duration of fever and with ≥ 5 days. Methods Children (≤ 15 years) with complete KD who visited the emergency department were enrolled from March 2012 through February 2018. The children were divided into the early (fever < 5 days) and late (fever ≥ 5 days) presenters. The baseline characteristics, APR levels, such as platelet count, and outcomes were compared between the 2 groups. Results A total of 145 children with complete KD were enrolled. Median age was 27.0 (interquartile range [IQR], 12.0-46.5) months, and boys accounted for 60.0%. The early presenters (63 [43.4%]) had a younger age (17.0 [IQR, 7.0-45.0] vs. 32.5 [IQR, 14.0-48.0] months; P = 0.006), shorter duration of fever (3.0 [IQR, 2.0-4.0] days vs. 6.0 [IQR, 5.0-7.0] days; P < 0.001), and a lower platelet count (336.7 ± 105.2 [× 103/μL] vs. 381.6 ± 121.8 [× 103/μL], P = 0.02) than the late presenters. The other APR levels, and frequency of resistance to intravenous immunoglobulin and coronary artery abnormalities showed no differences between the 2 groups. Conclusion Children with KD who visited with < 5 days duration of fever had a lower platelet count compared to those with ≥ 5 days. No differences were found in the other APR levels and the outcomes. It may be necessary to consider the differences in APR levels depending on duration of fever when treating children with KD.
Keywords	blood platelets ; c-reactive protein ; fever ; leukocyte count ; mucocutaneous lymph node syndrome ; Medicine ; R
Subject code	610
Language	English
Publishing date	2019-06-01T00:00:00Z
Publisher	Korean Society of Pediatric Emergency Medicine
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A predictive in vitro risk assessment platform for pro-arrhythmic toxicity using human 3D cardiac microtissues

Celinda M. Kofron / Tae Yun Kim / Fabiola Munarin / Arvin H. Soepriatna / Rajeev J. Kant / Ulrike Mende / Bum-Rak Choi / Kareen L. K. Coulombe

Scientific Reports, Vol 11, Iss 1, Pp 1-

2021 Volume 16

Abstract: Abstract Cardiotoxicity of pharmaceutical drugs, industrial chemicals, and environmental toxicants can be severe, even life threatening, which necessitates a thorough evaluation of the human response to chemical compounds. Predicting risks for arrhythmia ...

Abstract	Abstract Cardiotoxicity of pharmaceutical drugs, industrial chemicals, and environmental toxicants can be severe, even life threatening, which necessitates a thorough evaluation of the human response to chemical compounds. Predicting risks for arrhythmia and sudden cardiac death accurately is critical for defining safety profiles. Currently available approaches have limitations including a focus on single select ion channels, the use of non-human species in vitro and in vivo, and limited direct physiological translation. We have advanced the robustness and reproducibility of in vitro platforms for assessing pro-arrhythmic cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes and human cardiac fibroblasts in 3-dimensional microtissues. Using automated algorithms and statistical analyses of eight comprehensive evaluation metrics of cardiac action potentials, we demonstrate that tissue-engineered human cardiac microtissues respond appropriately to physiological stimuli and effectively differentiate between high-risk and low-risk compounds exhibiting blockade of the hERG channel (E4031 and ranolazine, respectively). Further, we show that the environmental endocrine disrupting chemical bisphenol-A (BPA) causes acute and sensitive disruption of human action potentials in the nanomolar range. Thus, this novel human 3D in vitro pro-arrhythmic risk assessment platform addresses critical needs in cardiotoxicity testing for both environmental and pharmaceutical compounds and can be leveraged to establish safe human exposure levels.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2021-05-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Myofibroblast senescence promotes arrhythmogenic remodeling in the aged infarcted rabbit heart

Brett C Baggett / Kevin R Murphy / Elif Sengun / Eric Mi / Yueming Cao / Nilufer N Turan / Yichun Lu / Lorraine Schofield / Tae Yun Kim / Anatoli Y Kabakov / Peter Bronk / Zhilin Qu / Patrizia Camelliti / Patrycja Dubielecka / Dmitry Terentyev / Federica del Monte / Bum-Rak Choi / John Sedivy / Gideon Koren

eLife, Vol

2023 Volume 12

Abstract: Progressive tissue remodeling after myocardial infarction (MI) promotes cardiac arrhythmias. This process is well studied in young animals, but little is known about pro-arrhythmic changes in aged animals. Senescent cells accumulate with age and ... ...

Abstract	Progressive tissue remodeling after myocardial infarction (MI) promotes cardiac arrhythmias. This process is well studied in young animals, but little is known about pro-arrhythmic changes in aged animals. Senescent cells accumulate with age and accelerate age-associated diseases. Senescent cells interfere with cardiac function and outcome post-MI with age, but studies have not been performed in larger animals, and the mechanisms are unknown. Specifically, age-associated changes in timecourse of senescence and related changes in inflammation and fibrosis are not well understood. Additionally, the cellular and systemic role of senescence and its inflammatory milieu in influencing arrhythmogenesis with age is not clear, particularly in large animal models with cardiac electrophysiology more similar to humans than previously studied animal models. Here, we investigated the role of senescence in regulating inflammation, fibrosis, and arrhythmogenesis in young and aged infarcted rabbits. Aged rabbits exhibited increased peri-procedural mortality and arrhythmogenic electrophysiological remodeling at the infarct border zone (IBZ) compared to young rabbits. Studies of the aged infarct zone revealed persistent myofibroblast senescence and increased inflammatory signaling over a 12-week timecourse. Senescent IBZ myofibroblasts in aged rabbits appear to be coupled to myocytes, and our computational modeling showed that senescent myofibroblast-cardiomyocyte coupling prolongs action potential duration (APD) and facilitates conduction block permissive of arrhythmias. Aged infarcted human ventricles show levels of senescence consistent with aged rabbits, and senescent myofibroblasts also couple to IBZ myocytes. Our findings suggest that therapeutic interventions targeting senescent cells may mitigate arrhythmias post-MI with age.
Keywords	cardiac arrhythmia ; sudden cardiac death ; myocardial infarction ; senescence ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
Subject code	610
Language	English
Publishing date	2023-05-01T00:00:00Z
Publisher	eLife Sciences Publications Ltd
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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