Publications by authors named "Yoojin Kwon"

7 Publications

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Coordinate regulation of the senescent state by selective autophagy.

Dev Cell 2021 May 28;56(10):1512-1525.e7. Epub 2021 Apr 28.

School of Biological Sciences, Seoul National University, Seoul 08826, South Korea. Electronic address:

Cellular senescence is a complex stress response implicated in aging. Autophagy can suppress senescence but is counterintuitively necessary for full senescence. Although its anti-senescence role is well described, to what extent autophagy contributes to senescence establishment and the underlying mechanisms is poorly understood. Here, we show that selective autophagy of multiple regulatory components coordinates the homeostatic state of senescence. We combined a proteomic analysis of autophagy components with protein stability profiling, identifying autophagy substrate proteins involved in several senescence-related processes. Selective autophagy of KEAP1 promoted redox homeostasis during senescence. Furthermore, selective autophagy limited translational machinery components to ameliorate senescence-associated proteotoxic stress. Lastly, selective autophagy of TNIP1 enhanced senescence-associated inflammation. These selective autophagy networks appear to operate in vivo senescence during human osteoarthritis. Our data highlight a caretaker role of autophagy in the stress support network of senescence through regulated protein stability and unravel the intertwined relationship between two important age-related processes.
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May 2021

Autophagy Is Pro-Senescence When Seen in Close-Up, but Anti-Senescence in Long-Shot.

Mol Cells 2017 Sep 20;40(9):607-612. Epub 2017 Sep 20.

School of Biological Sciences, Seoul National University, Seoul 08826, Korea.

When mammalian cells and animals face a variety of internal or external stresses, they need to make homeostatic changes so as to cope with various stresses. To this end, mammalian cells are equipped with two critical stress responses, autophagy and cellular senescence. Autophagy and cellular senescence share a number of stimuli including telomere shortening, DNA damage, oncogenic stress and oxidative stress, suggesting their intimate relationship. Autophagy is originally thought to suppress cellular senescence by removing damaged macromolecules or organelles, yet recent studies also indicated that autophagy promotes cellular senescence by facilitating the synthesis of senescence-associated secretory proteins. These seemingly opposite roles of autophagy may reflect a complex picture of autophagic regulation on cellular senescence, including different types of autophagy or a unique spatiotemporal activation of autophagy. Thus, a better understanding of autophagy process will lead us to not only elucidate the conundrum how autophagy plays dual roles in the regulation of cellular senescence but also helps the development of new therapeutic strategies for many human diseases associated with cellular senescence. We address the pro-senescence and anti-senescence roles of autophagy while focusing on the potential mechanistic aspects of this complex relationship between autophagy and cellular senescence.
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September 2017

PCNA-Dependent Cleavage and Degradation of SDE2 Regulates Response to Replication Stress.

PLoS Genet 2016 Dec 1;12(12):e1006465. Epub 2016 Dec 1.

Department of Pharmacological Sciences, Stony Brook University, Stony Brook, New York, United States of America.

Maintaining genomic integrity during DNA replication is essential for cellular survival and for preventing tumorigenesis. Proliferating cell nuclear antigen (PCNA) functions as a processivity factor for DNA replication, and posttranslational modification of PCNA plays a key role in coordinating DNA repair against replication-blocking lesions by providing a platform to recruit factors required for DNA repair and cell cycle control. Here, we identify human SDE2 as a new genome surveillance factor regulated by PCNA interaction. SDE2 contains an N-terminal ubiquitin-like (UBL) fold, which is cleaved at a diglycine motif via a PCNA-interacting peptide (PIP) box and deubiquitinating enzyme activity. The cleaved SDE2 is required for negatively regulating ultraviolet damage-inducible PCNA monoubiquitination and counteracting replication stress. The cleaved SDE2 products need to be degraded by the CRL4CDT2 ubiquitin E3 ligase in a cell cycle- and DNA damage-dependent manner, and failure to degrade SDE2 impairs S phase progression and cellular survival. Collectively, this study uncovers a new role for CRL4CDT2 in protecting genomic integrity against replication stress via regulated proteolysis of PCNA-associated SDE2 and provides insights into how an integrated UBL domain within linear polypeptide sequence controls protein stability and function.
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December 2016

Adoption of e-health technology by physicians: a scoping review.

J Multidiscip Healthc 2016 1;9:335-44. Epub 2016 Aug 1.

Department of Community Health Sciences, W21C Research and Innovation Centre, University of Calgary, Calgary.

Objective: The goal of this scoping review was to summarize the current literature identifying barriers and opportunities that facilitate adoption of e-health technology by physicians.

Design: Scoping review.

Setting: MEDLINE, EMBASE, and PsycINFO databases as provided by Ovid were searched from their inception to July 2015. Studies captured by the search strategy were screened by two reviewers and included if the focus was on barriers and facilitators of e-health technology adoption by physicians.

Results: Full-text screening yielded 74 studies to be included in the scoping review. Within those studies, eleven themes were identified, including cost and liability issues, unwillingness to use e-health technology, and training and support.

Conclusion: Cost and liability issues, unwillingness to use e-health technology, and training and support were the most frequently mentioned barriers and facilitators to the adoption of e-health technology. Government-level payment incentives and privacy laws to protect health information may be the key to overcome cost and liability issues. The adoption of e-health technology may be facilitated by tailoring to the individual physician's knowledge of the e-health technology and the use of follow-up sessions for physicians and on-site experts to support their use of the e-health technology. To ensure the effective uptake of e-health technologies, physician perspectives need to be considered in creating an environment that enables the adoption of e-health strategies.
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August 2016

Use of ward closure to control outbreaks among hospitalized patients in acute care settings: a systematic review.

Syst Rev 2015 Nov 7;4:152. Epub 2015 Nov 7.

W21C Research and Innovation Centre, Cumming School of Medicine, University of Calgary, GD01 TRW Building, 3280 Hospital Drive NW, Calgary, Alberta, Canada, T2N 4Z6.

Background: Though often used to control outbreaks, the efficacy of ward closure is unclear. This systematic review sought to identify studies defining and describing ward closure in outbreak control and to determine impact of ward closure as an intervention on outbreak containment.

Methods: We searched these databases with no language restrictions: MEDLINE, 1946 to 7 July 2014; EMBASE, 1974 to 7 July 2014; CINAHL, 1937 to 8 July 2014; and Cochrane Database of Systematic Reviews, 2005 to May 2014. We also searched the following: IndMED; LILACS; reference lists from retrieved articles; conference proceedings; and websites of the CDCP, the ICID, and the WHO. We included studies of patients hospitalized in acute care facilities; used ward closure as a control measure; used other control measures; and discussed control of the outbreak(s) under investigation. A component approach was used to assess study quality.

Results: We included 97 English and non-English observational studies. None included a controlled comparison between ward closure and other interventions. We found that ward closure was often used as part of a bundle of interventions but could not determine its direct impact separate from all the other interventions whether used in parallel or in sequence with other interventions. We also found no universal definition of ward closure which was widely accepted.

Conclusions: With no published controlled studies identified, ward closure for control of outbreaks remains an intervention that is not evidence based and healthcare personnel will need to continue to balance the competing risks associated with its use, taking into consideration the nature of the outbreak, the type of pathogen and its virulence, mode of transmission, and the setting in which it occurs. Our review has identified a major research gap in this area.
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November 2015

Identifying and removing duplicate records from systematic review searches.

J Med Libr Assoc 2015 Oct;103(4):184-8

Objective: The purpose of this study was to compare effectiveness of different options for de-duplicating records retrieved from systematic review searches.

Methods: Using the records from a published systematic review, five de-duplication options were compared. The time taken to de-duplicate in each option and the number of false positives (were deleted but should not have been) and false negatives (should have been deleted but were not) were recorded.

Results: The time for each option varied. The number of positive and false duplicates returned from each option also varied greatly.

Conclusion: The authors recommend different de-duplication options based on the skill level of the searcher and the purpose of de-duplication efforts.
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October 2015

An assessment of the efficacy of searching in biomedical databases beyond MEDLINE in identifying studies for a systematic review on ward closures as an infection control intervention to control outbreaks.

Syst Rev 2014 Nov 11;3:135. Epub 2014 Nov 11.

Health Sciences Library, Libraries and Cultural Resources, University of Calgary, HSC 1450, Health Sciences Centre, 3330 Hospital Drive NW, Calgary, Alberta T2N 4N1, Canada.

Background: The purpose of our study is to determine the value and efficacy of searching biomedical databases beyond MEDLINE for systematic reviews.

Methods: We analyzed the results from a systematic review conducted by the authors and others on ward closure as an infection control practice. Ovid MEDLINE including In-Process & Other Non-Indexed Citations, Ovid Embase, CINAHL Plus, LILACS, and IndMED were systematically searched for articles of any study type discussing ward closure, as were bibliographies of selected articles and recent infection control conference abstracts. Search results were tracked, recorded, and analyzed using a relative recall method. The sensitivity of searching in each database was calculated.

Results: Two thousand ninety-five unique citations were identified and screened for inclusion in the systematic review: 2,060 from database searching and 35 from hand searching and other sources. Ninety-seven citations were included in the final review. MEDLINE and Embase searches each retrieved 80 of the 97 articles included, only 4 articles from each database were unique. The CINAHL search retrieved 35 included articles, and 4 were unique. The IndMED and LILACS searches did not retrieve any included articles, although 75 of the included articles were indexed in LILACS. The true value of using regional databases, particularly LILACS, may lie with the ability to search in the language spoken in the region. Eight articles were found only through hand searching.

Conclusions: Identifying studies for a systematic review where the research is observational is complex. The value each individual study contributes to the review cannot be accurately measured. Consequently, we could not determine the value of results found from searching beyond MEDLINE, Embase, and CINAHL with accuracy. However, hand searching for serendipitous retrieval remains an important aspect due to indexing and keyword challenges inherent in this literature.
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November 2014