Publications by authors named "Ju-Young Bae"

15 Publications

  • Page 1 of 1

Coombs-negative hemolytic anemia in a male with COVID-19.

Clin Case Rep 2021 Jul 6;9(7):e04503. Epub 2021 Jul 6.

Division of Hematology and Medical Oncology Greenwich Hospital Yale-New Haven Health System Greenwich CT USA.

This case illustrates the need to consider SARS-CoV-2 infection as a catalyst for Coombs-negative hemolytic anemia as well as the potential for IVIG to serve as an effective treatment for the condition.
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http://dx.doi.org/10.1002/ccr3.4503DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8259792PMC
July 2021

Seronegative Goodpasture's syndrome associated with organising pneumonia.

BMJ Case Rep 2021 Feb 9;14(2). Epub 2021 Feb 9.

Internal Medicine, Greenwich Hospital/Yale-New Haven Health, Greenwich, Connecticut, USA.

Goodpasture's syndrome is a rare vasculitis associated with anti-glomerular basement membrane (anti-GBM) autoantibodies that target type IV collagen found in the basement membranes of glomeruli and alveoli. We present a case of a 79-year-old man with seronegative Goodpasture's syndrome with predominant respiratory symptoms and mild acute kidney injury that initially improved. Final diagnosis was made by immunofluorescent staining on open lung biopsy which also revealed concomitant organising pneumonia. The patient underwent treatment with corticosteroids, cyclophosphamide, haemodialysis and plasmapheresis. This was an atypical presentation wherein the patient only exhibited pulmonary symptoms early in the course of illness in the setting of negative anti-GBM antibody serum testing, which made diagnosis challenging. With this case, we emphasise that clinicians should have a high suspicion for Goodpasture's syndrome in the setting of unexplained severe pulmonary or renal disease despite negative anti-GBM antibody testing.
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http://dx.doi.org/10.1136/bcr-2020-239390DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7875259PMC
February 2021

Diagnosis and treatment of transthyretin-related amyloidosis cardiomyopathy.

Clin Cardiol 2020 Nov 29;43(11):1223-1231. Epub 2020 Jul 29.

Molecular Cardiology Research, Texas Heart Institute, Houston, Texas, USA.

Transthyretin-related amyloidosis (ATTR) is a subgroup of amyloidosis that results from extracellular misassembled and toxic amyloid deposits affecting multiple organ systems, and cardiac tissues in particular. Because ATTR often presents as heart failure with preserved ejection fraction (HFpEF), it has been largely underdiagnosed. Once considered incurable with a grave prognosis, ATTR cardiomyopathy has seen the development of promising alternatives for diagnosis and treatment, with early diagnosis and treatment of ATTR cardiomyopathy highly beneficial due to its high mortality rate. For instance, diagnosing ATTR cardiomyopathy previously required a cardiac biopsy, but new modalities, such as cardiac magnetic resonance imaging and radionuclide bone scans, show promise in accurately diagnosing ATTR cardiomyopathy. Ongoing research and clinical trials have focused on identifying new treatments which primarily target amyloid fiber formation by inhibiting TTR gene expression, stabilizing the TTR tetramer, preventing oligomer aggregation, or affecting degradation of amyloid fibers. In this review, we describe the advances made in the diagnosis and treatment of ATTR in order to increase awareness of the disease and encourage a lower threshold for ATTR workup. Our review also highlights the need for improving the screening, diagnosis, and treatment guidelines for ATTR cardiomyopathy.
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http://dx.doi.org/10.1002/clc.23434DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7661658PMC
November 2020

System χ overexpression prevents 2-deoxy-d-ribose-induced β-cell damage.

Free Radic Biol Med 2020 06 16;153:17-25. Epub 2020 Apr 16.

Department of Internal Medicine, Jeju National University School of Medicine, 15 Aran 13-gil, Jeju, 63241, Republic of Korea; Department of Internal Medicine, Jeju National University Hospital, 15 Aran 13-gil, Jeju, 63241, Republic of Korea. Electronic address:

Pancreatic β-cells are vulnerable to oxidative stress, which promotes β-cell failure in type 2 diabetes. System χ is a sodium-independent, cystine/glutamate antiporter that mediates the exchange of extracellular l-cystine and intracellular l-glutamate. The import of l-cystine through this transporter is the rate-limiting step in the glutathione (GSH) biosynthesis pathway that plays a significant role in antioxidative defense. Previously, we reported that 2-deoxy-d-ribose (dRib) induces oxidative damage through GSH depletion in pancreatic β-cells. In the current study, we elucidated the mechanism underlying the oxidative stress-induced β-cell damage. We measured the intracellular l-[C]cystine uptake, GSH content, reactive oxygen species (ROS) levels, cytotoxicity, and apoptosis in rat insulinoma cell line, RINm5F. Treatment of dRib decreased the intracellular l-[C]cystine uptake and GSH content and increased the intracellular ROS levels, cytotoxicity, and apoptosis in a time- and dose-dependent manner. Conversely, 2-mercaptoethanol (2-ME), a cystine uptake enhancer, recovered the dRib-induced decrease in l-[C]cystine uptake, GSH content, and cell viability in a Na-independent manner. In the case of isolated islets, dRib dose-dependently decreased the intracellular l-[C]cystine uptake and cell viability; however, dRib-induced cytotoxicity was completely recovered by adding N-acetyl cysteine (NAC). To confirm that system χ mediates the oxidative stress-induced β-cell damage, we overexpressed xCT (the substrate-specific subunit of system χ) using a lentiviral vector in RINm5F cells. Overexpression of xCT fully recovered the dRib-induced decrease in l-[C]cystine uptake and GSH content and prevented the dRib-induced increase in ROS levels, cytotoxicity, and apoptosis. The overexpression of xCT showed a protective effect against dRib-induced oxidative damage in RINm5F cells. Our study showed that dRib depletes intracellular GSH content through inhibition of cystine transport via system χ in β-cells.
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http://dx.doi.org/10.1016/j.freeradbiomed.2020.04.012DOI Listing
June 2020

Barley RNA viromes in six different geographical regions in Korea.

Sci Rep 2018 09 5;8(1):13237. Epub 2018 Sep 5.

Research Institute of Agriculture and Life Sciences, College of Agriculture and Life Sciences, Seoul National University, Seoul, 08826, Republic of Korea.

Barley is a kind of cereal grass belonging to the family Poaceae. To examine viruses infecting winter barley in Korea, we carried out a comprehensive study of barley RNA viromes using next-generation sequencing (NGS). A total of 110 barley leaf samples from 17 geographical locations were collected. NGS followed by extensive bioinformatics analyses revealed six different barley viromes: Barley yellow mosaic virus (BaYMV), Barley mild mosaic virus (BaMMV), Barley yellow dwarf virus (BYDV), Hordeum vulgare endornavirus (HvEV), and Barley virus G (BVG). BaYMV and HvEV were identified in all libraries, while other viruses were identified in some specific library. Based on the number of virus-associated reads, BaYMV was a dominant virus infecting winter barley in Korea causing yellow disease symptoms. We obtained nearly complete genomes of six BaYMV isolates and two BaMMV isolates. Phylogenetic analyses indicate that BaYMV and BaMMV were largely grouped based on geographical regions such as Asia and Europe. Single nucleotide polymorphisms analyses suggested that most BaYMV and BaMMV showed strong genetic variations; however, BaYMV isolate Jeonju and BaMMV isolate Gunsan exhibited a few and no SNPs, respectively, suggesting low level of genetic variation. Taken together, this is the first study of barley RNA viromes in Korea.
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http://dx.doi.org/10.1038/s41598-018-31671-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6125401PMC
September 2018

Complete genome sequence of rice virus A, a new member of the family Tombusviridae.

Arch Virol 2017 Oct 10;162(10):3247-3250. Epub 2017 Jul 10.

Plant Systems Engineering Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 305-806, South Korea.

An evaluation of the virus population in rice plants using next-generation sequencing technologies resulted in the discovery of a new RNA virus, tentatively named rice virus A (RVA). The complete RVA genome sequence was determined and analyzed, revealing a genome organization resembling that of viruses classified in the genera Aureusvirus, Tombusvirus and Zeavirus within the family Tombusviridae. With 4,832 nucleotides, the RVA genome may be the largest monopartite genome sequenced to date in the family Tombusviridae. The 453-amino acid RVA coat protein shares the highest identity with the gp3 protein of an unclassified carascovirus, SF1 (GenBank accession no. KF510027) isolated from San Francisco wastewater, rather than the coat protein of any known member of the family Tombusviridae. These novel characteristics represent a significant divergence from the genomes of viruses belonging to the sixteen existing genera of the family Tombusviridae, demonstrating that RVA is likely a new family member.
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http://dx.doi.org/10.1007/s00705-017-3472-4DOI Listing
October 2017

P2X7 receptor and NLRP3 inflammasome activation in head and neck cancer.

Oncotarget 2017 Jul;8(30):48972-48982

Department of Physiology, School of Dentistry, Seoul National University, Seoul 110-749, Korea.

In this study, we investigated purinergic receptor P2X7 and NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome expressions, and their role in head and neck cancer. We found upregulation of purinergic receptor P2X7 and all NLRP3 inflammasome components in biopsied head and neck squamous cell carcinoma tissues. Similarly, the expression of purinergic receptor P2X7, apoptosis-associated speck-like protein containing CARD, and pro-form caspase 1 in A253 cells derived from epidermoid carcinoma were highly upregulated in comparison to normal Human Salivary Gland cell line. Active caspase-1 and its final product, active interleukin-1β, both increased in primed A253 cells stimulated with purinergic receptor P2X7 agonists, while this elevated NLRP3 inflammasome activity was suppressed by purinergic receptor P2X7 antagonists. However, we observed none of these effects in Human Salivary Gland cells. Inhibition of both NLRP3 inflammasome and purinergic receptor P2X7 led to the significant cell death of primed A253 cells, but had no effect on the viability of primed HSG cells or the primary cultured human fibroblast cells. Furthermore, inhibition of either purinergic receptor P2X7 or NLRP3 inflammasome decreased invasiveness of A253, and this effect became more evident when both purinergic receptor P2X7 and NLRP3 inflammasome were simultaneously blocked. Therefore, it is concluded that the purinergic receptor P2X7 and the activation of NLRP3 inflammasome play important roles in the survival and invasiveness of head and neck squamous cell carcinoma in humans.
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http://dx.doi.org/10.18632/oncotarget.16903DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5564741PMC
July 2017

Induction of the viable but nonculturable state of Ralstonia solanacearum by low temperature in the soil microcosm and its resuscitation by catalase.

PLoS One 2014 8;9(10):e109792. Epub 2014 Oct 8.

Department of Applied Bioscience, Dong-A University, Busan, Republic of Korea.

Ralstonia solanacearum is the causal agent of bacterial wilt on a wide variety of plants, and enters a viable but nonculturable (VBNC) state under stress conditions in soil and water. Here, we adopted an artificial soil microcosm (ASM) to investigate the VBNC state of R. solanacearum induced by low temperature. The culturability of R. solanacearum strains SL341 and GMI1000 rapidly decreased at 4°C in modified ASM (mASM), while it was stably maintained at 25°C in mASM. We hypothesized that bacterial cells at 4°C in mASM are viable but nonculturable. Total protein profiles of SL341 cells at 4°C in mASM did not differ from those of SL341 culturable cells at 25°C in mASM. Moreover, the VBNC cells maintained in the mASM retained respiration activity. Catalase treatment effectively restored the culturability of nonculturable cells in mASM, while temperature increase or other treatments used for resuscitation of other bacteria were not effective. The resuscitated R. solanacearum from VBNC state displayed normal level of bacterial virulence on tomato plants compared with its original culturable bacteria. Expression of omp, oxyR, rpoS, dps, and the 16S rRNA gene quantified by RT-qPCR did not differ significantly between the culturable and VBNC states of R. solanacearum. Our results suggested that the VBNC bacterial cells in mASM induced by low temperature exist in a physiologically unique state.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0109792PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4190316PMC
October 2015

Self-oligomerization of the CARD domain prevents complex formation in the CARMA1 signalosome.

Int J Mol Med 2013 May 19;31(5):1280-7. Epub 2013 Mar 19.

School of Biotechnology and the Graduate School of Biochemistry, Yeungnam University, Gyeongsan, Republic of Korea.

The CARMA1 signalosome composed of CARMA1, BCL10 and MALT1 plays a pivotal role in antigen receptor-mediated lymphocyte activation via the NF-κB pathway. For assembly of the CARMA1 signalosome, BCL10 functions as an adaptor protein that interacts with CARMA1 via the CARD-CARD interaction and with MALT1 via interaction between the C-terminal Ser/Thr-rich region of BCL10 and the first Ig domain of MALT1. Despite the biological importance of the CARMA1 signalosome, structural and biochemical studies have been limited as CARD-containing proteins are prone to aggregation under physiological conditions. In the present study, we successfully purified and characterized CARMA1 CARD and BCL10 CARD and showed that both CARMA1 CARD and BCL10 CARD easily self-oligomerized under physiological conditions. This self-oligomerization of the CARD domain prevents complex formation in the CARMA1 signalosome in vitro. Finally, we propose an interaction mode between CARMA1 CARD and BCL10 CARD based on a structure-based modeling study.
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http://dx.doi.org/10.3892/ijmm.2013.1307DOI Listing
May 2013

Biocontrol potential of a lytic bacteriophage PE204 against bacterial wilt of tomato.

J Microbiol Biotechnol 2012 Dec;22(12):1613-20

Department of Medical Bioscience, Dong-A University, Busan, Korea.

Bacterial wilt caused by Ralstonia solanacearum is a devastating disease of many economically important crops. Since there is no promising control strategy for bacterial wilt, phage therapy could be adopted using virulent phages. We used phage PE204 as a model lytic bacteriophage to investigate its biocontrol potential for bacterial wilt on tomato plants. The phage PE204 has a short-tailed icosahedral structure and double-stranded DNA genome similar to that of the members of Podoviridae. PE204 is stable under a wide range of temperature and pH, and is also stable in the presence of the surfactant Silwet L-77. An artificial soil microcosm (ASM) to study phage stability in soil was adopted to investigate phage viability under a controlled system. Whereas phage showed less stability under elevated temperature in the ASM, the presence of host bacteria helped to maintain a stable phage population. Simultaneous treatment of phage PE204 at 10(8) PFU/ml with R. solanacearum on tomato rhizosphere completely inhibited bacterial wilt occurrence, and amendment of Silwet L-77 at 0.1% to the phage suspension did not impair the disease control activity of PE204. The biocontrol activities of phage PE204 application onto tomato rhizosphere before or after R. solanacearum inoculation were also investigated. Whereas pretreatment with the phage was not effective in the control of bacterial wilt, post-treatment of PE204 delayed bacterial wilt development. Our results suggested that appropriate application of lytic phages to the plant root system with a surfactant such as Silwet L-77 could be used to control the bacterial wilt of crops.
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http://dx.doi.org/10.4014/jmb.1208.08072DOI Listing
December 2012

Crystallization and preliminary X-ray crystallographic studies of the PYD domain of human NALP3.

Acta Crystallogr Sect F Struct Biol Cryst Commun 2011 Nov 27;67(Pt 11):1421-4. Epub 2011 Oct 27.

School of Biotechnology and Graduate School of Biochemistry, Yeungnam University, Gyeongsan, Republic of Korea.

The NALP3 inflammasome is a macromolecular complex that is responsible for the innate immune response against infection by bacterial and viral pathogens. The NALP3 inflammasome is composed of three protein components: NALP3, ASC and caspase 1. Interaction between NALP3 and ASC via PYD domains is critical for the assembly of the NALP3 inflammasome. In this study, human NALP3 PYD, corresponding to amino acids 3-110, was overexpressed in Escherichia coli using engineered C-terminal His tags. NALP3 PYD was then purified to homogeneity and crystallized at 293 K. Finally, X-ray diffraction data were collected to a resolution of 1.7 Å from a crystal belonging to the primitive monoclinic space group P2(1), with unit-cell parameters a = 42.03, b = 60.14, c = 51.61 Å, β = 107.40°.
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http://dx.doi.org/10.1107/S1744309111035937DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3212466PMC
November 2011

Crystal structure of NALP3 protein pyrin domain (PYD) and its implications in inflammasome assembly.

J Biol Chem 2011 Nov 31;286(45):39528-36. Epub 2011 Aug 31.

Graduate School of Biochemistry, and Research Institute of Protein Sensor, Yeungnam University, Gyeongsan, South Korea.

NALP3 inflammasome, composed of the three proteins NALP3, ASC, and Caspase-1, is a macromolecular complex responsible for the innate immune response against infection with bacterial and viral pathogens. Formation of the inflammasome can lead to the activation of inflammatory caspases, such as Caspase-1, which then activate pro-inflammatory cytokines by proteolytic cleavage. The assembly of the NALP3 inflammasome depends on the protein-interacting domain known as the death domain superfamily. NALP3 inflammasome is assembled via a pyrin domain (PYD)/PYD interaction between ASC and NALP3 and a caspase recruitment domain/caspase recruitment domain interaction between ASC and Caspase-1. As a first step toward elucidating the molecular mechanisms of inflammatory caspase activation by formation of inflammasome, we report the crystal structure of the PYD from NALP3 at 1.7-Å resolution. Although NALP3 PYD has the canonical six-helical bundle structural fold similar to other PYDs, the high resolution structure reveals the possible biologically important homodimeric interface and the dynamic properties of the fold. Comparison with other PYD structures shows both similarities and differences that may be functionally relevant. Structural and sequence analyses further implicate conserved surface residues in NALP3 PYD for ASC interaction and inflammasome assembly. The most interesting aspect of the structure was the unexpected disulfide bond between Cys-8 and Cys-108, which might be important for regulation of the activity of NALP3 by redox potential.
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http://dx.doi.org/10.1074/jbc.M111.278812DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3234776PMC
November 2011

Crystallization and preliminary X-ray crystallographic studies of β-transaminase from Mesorhizobium sp. strain LUK.

Acta Crystallogr Sect F Struct Biol Cryst Commun 2011 Feb 22;67(Pt 2):231-3. Epub 2011 Jan 22.

School of Biotechnology, Yeungnam University, Gyeongsan, Republic of Korea.

β-Transaminase (β-TA) catalyzes the transamination reaction between β-aminocarboxylic acids and keto acids. This enzyme is a particularly suitable candidate for use as a biocatalyst for the asymmetric synthesis of enantiochemically pure β-amino acids for pharmaceutical purposes. The β-TA from Mesorhizobium sp. strain LUK (β-TAMs) belongs to a novel class in that it shows β-transaminase activity with a broad and unique substrate specificity. In this study, β-TAMs was overexpressed in Escherichia coli with an engineered C-terminal His tag. β-TAMs was then purified to homogeneity and crystallized at 293 K. X-ray diffraction data were collected to a resolution of 2.5 Å from a crystal that belonged to the orthorhombic space group C222(1), with unit-cell parameters a = 90.91, b = 192.17, c = 52.75 Å.
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http://dx.doi.org/10.1107/S1744309110050876DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3034615PMC
February 2011

Crystallization and preliminary X-ray crystallographic studies of ω-transaminase from Vibrio fluvialis JS17.

Acta Crystallogr Sect F Struct Biol Cryst Commun 2010 Aug 29;66(Pt 8):923-5. Epub 2010 Jul 29.

School of Biotechnology and Graduate School of Biochemistry at Yeungnam University, Gyeongsan, Republic of Korea.

Omega-transaminase (ω-TA) catalyzes the transfer of an amino group from a non-alpha-position amino acid or an amine compound with no carboxylic group to an amino acceptor. ω-TA from Vibrio fluvialis JS17 (ω-TAVf) is a novel amine:pyruvate transaminase that is capable of stereoselective transamination of aryl chiral amines. In this study, omega-TAVf was overexpressed in Escherichia coli with engineered C-terminal His tags. ω-TAVf was then purified to homogeneity and crystallized at 292 K. X-ray diffraction data were collected to a resolution of 2.5 A from a crystal belonging to the orthorhombic space group P2(1)2(1)2(1), with unit-cell parameters a=78.43, b=95.95, c=122.89 A.
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http://dx.doi.org/10.1107/S1744309110021573DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2917292PMC
August 2010

Identification and analysis of dominant negative mutants of RAIDD and PIDD.

Biochim Biophys Acta 2010 Jul 18;1804(7):1557-63. Epub 2010 Apr 18.

Department of Biochemistry, School of Biotechnology, Yeungnam University, Gyeongsan, South Korea.

Caspases are cysteine proteases that are essential during the initiation and execution of apoptosis and inflammation. The formation of large oligomeric protein complexes is critical to the activation of caspases in apoptotic and inflammatory signaling pathways. These oligomeric protein complexes function as a platform to recruit caspases, which leads to caspase activation via a proximity-induced mechanism. One well-known oligomeric caspase-activating complex is the PIDDosome for caspase-2 activation, which is composed of 3 protein components, PIDD, RAIDD and Caspase-2. Despite the significant role that caspase-2 activated by PIDDosome plays during genotoxic stress-induced apoptosis, the oligomerization mechanism and the method by which the caspase-activating process is mediated by the formation of PIDDosome is currently not well understood. Here, we show that the assembly mechanism of the core of PIDDosome is time-dependent and salt concentration-dependent. In addition, we demonstrate that point mutations on RAIDD (R147E) and on PIDD (Y814A) exert a dominant negative effect on the formation of the PIDDosome, and that this effect cannot be applied after the PIDDosome has been formed.
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http://dx.doi.org/10.1016/j.bbapap.2010.04.006DOI Listing
July 2010