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Article ; Online: MicroRNA-212-5p and its target PAFAH1B2 suppress vascular proliferation and contraction via the downregulation of RhoA.

Gwi Ran Kim / Tingwei Zhao / Hae Jin Kee / Seung-Jung Kee / Myung Ho Jeong

PLoS ONE, Vol 16, Iss 3, p e

2021 Volume 0249146

Abstract: Vascular remodeling and contraction contribute to the development of hypertension. We investigated the role of miR-212-5p and its downstream target in vascular smooth muscle cell (VSMC) proliferation, migration, and contraction. MicroRNA microarray and ... ...

Abstract	Vascular remodeling and contraction contribute to the development of hypertension. We investigated the role of miR-212-5p and its downstream target in vascular smooth muscle cell (VSMC) proliferation, migration, and contraction. MicroRNA microarray and PCR analyses showed that miR-212-5p expression was increased with angiotensin II treatment in vivo and in vitro. Moreover, miR-212-5p mimic treatment attenuated and miR-212-5p inhibitor treatment increased VSMC proliferation and migration. Additionally, miR-212-5p mimic treatment suppressed VSMC contraction and related gene expression [Ras homolog gene family member A (RhoA) and Rho-associated protein kinase 2], while miR-212-5p inhibitor treatment exerted opposite effects. Bioinformatics analysis revealed that platelet-activating factor acetylhydrolase 1B2 (PAFAH1B2) is a target of miR-212-5p. miR-212-5p mimic treatment significantly reduced and miR-212-5p inhibitor treatment increased PAFAH1B2 expression. Furthermore, PAFAH1B2 expression was decreased in angiotensin II-treated aortic tissues and VSMCs. PAFAH1B2 was ubiquitously expressed in most adult rat tissues. In the vasculature, PAFAH1B2 was only distributed in the cytoplasm. PAFAH1B2 overexpression decreased A10 cell proliferation, while PAFAH1B2 knockdown increased A10 cell proliferation and cyclin D1 mRNA levels. PAFAH1B2 knockdown stimulated VSMC contraction and RhoA expression. These results suggest that miR-212-5p and PAFAH1B2 are novel negative regulators of VSMC proliferation, migration, and contraction in hypertension.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Under-diagnosis of vector-borne diseases among individuals suspected of having Scrub Typhus in South Korea.

Eun Jeong Won / Seong Hoon Kim / Kyeong Hwan Byeon / Chae-Hyeon Jeon / Seung-Ji Kang / Joo-Heon Park / Seung-Jung Kee / Hyun-Woo Choi

PLoS ONE, Vol 18, Iss 6, p e

2023 Volume 0286631

Abstract: Due to environmental and ecological changes and suitable habitats, the occurrence of vector-borne diseases is increasing. We investigated the seroprevalence of four major vector-borne pathogens in human patients with febrile illness who were clinically ... ...

Abstract	Due to environmental and ecological changes and suitable habitats, the occurrence of vector-borne diseases is increasing. We investigated the seroprevalence of four major vector-borne pathogens in human patients with febrile illness who were clinically suspected of having Scrub Typhus (ST) caused by Orientia tsutsugamushi. A total of 187 samples (182 patient whole blood and sera samples, including 5 follow-up) were collected. Antibodies to Anaplasma phagocytophilum, Ehrlichia chaffeensis, Borrelia burgdorferi, and Bartonella henselae were tested by using indirect immunofluorescence assays. Molecular diagnoses were performed using real-time PCR. Of the 182 cases, 37 (20.3%) cases were designated as confirmed cases of ST, and the remaining 145 (79.7%) cases as other febrile diseases (OFDs). The seroprevalence of A. phagocytophilum, E. chaffeensis, B. burgdorferi, and B. henselae was 51.4% (19/37), 10.8% (4/37), 86.5% (32/37), and 10.8% (4/37) among the ST group, and 42.8% (62/145), 10.4% (19/145), 57.7% (105/145), and 15.9% (29/145) among the OFD group, respectively. There were no significant differences in the seroprevalence between the ST and the OFD groups. Considering the co-occurrence, 89.0% (162/182) had at least one antibody to tick-borne pathogens, 37.0% (60/162) were positive for two pathogens, 17.3% (28/162) for three pathogens, and 6.2% (10/162) for four pathogens. In real-time PCR, O. tsutsugamushi was positive in 16 cases [15 (40.5%) in ST group and 1 (2.2%) in OFD group], and the four other pathogens were negative in all cases except one confirmed as anaplasmosis. In evaluating the five follow-up samples, the appearance of new antibodies or an increase in the pre-existing antibody titers was detected. Our data highlighted that acute febrile illness and manifestations suggestive of a vector-borne infection must be recognized and further considered for coinfections in clinical practice and the laboratory.
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 ; Online: Protocatechuic acid attenuates isoproterenol-induced cardiac hypertrophy via downregulation of ROCK1–Sp1–PKCγ axis

Liyan Bai / Hae Jin Kee / Xiongyi Han / Tingwei Zhao / Seung-Jung Kee / Myung Ho Jeong

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

2021 Volume 16

Abstract: Abstract Cardiac hypertrophy is an adaptive response of the myocardium to pressure overload or adrenergic agonists. Here, we investigated the protective effects and the regulatory mechanism of protocatechuic acid, a phenolic compound, using a mouse model ...

Abstract	Abstract Cardiac hypertrophy is an adaptive response of the myocardium to pressure overload or adrenergic agonists. Here, we investigated the protective effects and the regulatory mechanism of protocatechuic acid, a phenolic compound, using a mouse model of isoproterenol-induced cardiac hypertrophy. Our results demonstrated that protocatechuic acid treatment significantly downregulated the expression of cardiac hypertrophic markers (Nppa, Nppb, and Myh7), cardiomyocyte size, heart weight to body weight ratio, cross-sectional area, and thickness of left ventricular septum and posterior wall. This treatment also reduced the expression of isoproterenol-induced ROCK1, Sp1, and PKCγ both in vivo and in vitro. To investigate the mechanism, we performed knockdown and overexpression experiments. The knockdown of ROCK1, Sp1, or PKCγ decreased the isoproterenol-induced cell area and the expression of hypertrophic markers, while the overexpression of Sp1 or PKCγ increased the levels of hypertrophic markers. Protocatechuic acid treatment reversed these effects. Interestingly, the overexpression of Sp1 increased cell area and induced PKCγ expression. Furthermore, experiments using transcription inhibitor actinomycin D showed that ROCK1 and Sp1 suppression by protocatechuic acid was not regulated at the transcriptional level. Our results indicate that protocatechuic acid acts via the ROCK1/Sp1/PKCγ axis and therefore has promising therapeutic potential as a treatment for cardiac hypertrophy.
Keywords	Medicine ; R ; Science ; Q
Subject code	616
Language	English
Publishing date	2021-08-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Natural Killer T Cells Are Numerically and Functionally Deficient in Patients with Trauma

Young-Goun Jo / Jung-Chul Kim / Hye-Mi Jin / Young-Nan Cho / Seung-Jung Kee / Yong-Wook Park

Journal of Innate Immunity, Pp 1-

2020 Volume 11

Abstract: Natural killer T (NKT) cells rapidly produce Th1 and Th2 cytokines such as interferon-γ (IFN-γ) and interleukin (IL)-4. This study examined the frequency and function of NKT cells in trauma patients. Frequencies, proliferative responses to α- ... ...

Abstract	Natural killer T (NKT) cells rapidly produce Th1 and Th2 cytokines such as interferon-γ (IFN-γ) and interleukin (IL)-4. This study examined the frequency and function of NKT cells in trauma patients. Frequencies, proliferative responses to α-galactosylceramide (α-GalCer), and Th1/Th2 cytokine secretion levels of NKT cells in peripheral blood mononuclear cells from trauma patients and healthy controls (HC) were measured by flow cytometry. Circulating NKT cell levels were significantly reduced in trauma patients. Proliferation and IFN-γ production of circulating NKT cells in response to α-GalCer were markedly decreased in trauma patients. CD69 expression levels produced by NKT cells were significantly upregulated in trauma patients compared to those in HC. In addition, annexin V+ NKT cells were profoundly increased in trauma patients after α-GalCer stimulation. Trauma patients had higher plasma levels of IL-6, IL-8, and TNF-α compared to HC. In particular, the proliferative response of NKT cells to α-GalCer was significantly decreased in the presence of these cytokines. Such decrease was partially recovered after treatment with blocking antibodies against these cytokines. This study demonstrates that circulating NKT cells are numerically deficient and functionally impaired in IFN-γ production in trauma patients. These findings provide an important insight into the trauma-related innate immune response.
Keywords	α-galactosylceramide ; cytokine ; natural killer t cells ; proliferation ; trauma ; Medicine ; R ; Internal medicine ; RC31-1245
Subject code	610 ; 616
Language	English
Publishing date	2020-05-01T00:00:00Z
Publisher	Karger Publishers
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Activation, Deficiency, and Reduced IFN-γ Production of Mucosal-Associated Invariant T Cells in Patients with Inflammatory Bowel Disease

Jae Kyun Ju / Young-Nan Cho / Ki-Jeong Park / Han Deok Kwak / Hye-Mi Jin / Seon-Young Park / Hyun Soo Kim / Seung-Jung Kee / Yong-Wook Park

Journal of Innate Immunity, Pp 1-

2020 Volume 12

Abstract: Mucosal-associated invariant T (MAIT) cells are innate-like T cells that can activate either in response to T-cell receptor (TCR) engagement or through activating cytokines and play an important role in autoimmune disorders. The study examined the level ... ...

Abstract	Mucosal-associated invariant T (MAIT) cells are innate-like T cells that can activate either in response to T-cell receptor (TCR) engagement or through activating cytokines and play an important role in autoimmune disorders. The study examined the level and function of MAIT cells in patients with inflammatory bowel disease (IBD). Circulating MAIT cell levels were significantly reduced in IBD patients. This MAIT cell deficiency was correlated with IBD disease activity grades, hemoglobin, and CRP. IFN-γ production of circulating MAIT cells in response to both MHC class 1b-like related protein (MR1)-dependent and -independent stimulations was decreased in IBD patients, which was partially associated with reduced activation of nuclear factor of activated T cells 1 (NFAT1) transcription factor, a main regulator of IFN-γ production. Expression levels of CD69, programmed death-1 (PD-1), and annexin V in MAIT cells were elevated in IBD patients. CCL20, CXCL10, CXCL16, and CCL25 were expressed higher in inflamed intestinal tissues than in noninflamed tissues. This study demonstrates that circulating MAIT cells are activated and numerically and functionally deficient in IBD patients. Furthermore, activated MAIT cells have the potential to migrate to inflamed tissues. These findings suggest an important role of MAIT cells in mucosal immunity in IBD.
Keywords	inflammatory bowel disease ; interferon-γ ; mucosal-associated invariant t cells ; migration ; activation ; Medicine ; R ; Internal medicine ; RC31-1245
Subject code	610 ; 616
Language	English
Publishing date	2020-06-01T00:00:00Z
Publisher	Karger Publishers
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Gentisic acid prevents the transition from pressure overload-induced cardiac hypertrophy to heart failure

Simei Sun / Hae Jin Kee / Yuhee Ryu / Sin Young Choi / Gwi Ran Kim / Hyung-Seok Kim / Seung-Jung Kee / Myung Ho Jeong

Scientific Reports, Vol 9, Iss 1, Pp 1-

2019 Volume 14

Abstract: Abstract We previously reported that gentisic acid attenuates cardiac hypertrophy and fibrosis in transverse aortic constriction (TAC)-induced cardiac hypertrophy. Here, we examined whether gentisic acid prevents the development of heart failure. Heart ... ...

Abstract	Abstract We previously reported that gentisic acid attenuates cardiac hypertrophy and fibrosis in transverse aortic constriction (TAC)-induced cardiac hypertrophy. Here, we examined whether gentisic acid prevents the development of heart failure. Heart failure was induced in mice via chronic TAC. Mice were administered the vehicle, gentisic acid (10 and 100 mg∙kg−1∙day−1), or bisoprolol (0.5 mg∙kg−1∙day−1) orally for 3 weeks, beginning 3 weeks after TAC. After oral administration of gentisic acid (2000 mg∙kg−1), no significant differences in organ weight, histology, or analyzed serum and hematological parameters were observed between female mice in the control and gentisic acid-treated groups. Gentisic acid administration inhibited cardiac dysfunction in a dose-dependent manner, and reduced cardiac hypertrophy and fibrosis, as was revealed via western blotting, quantitative real-time PCR, and Masson’s trichrome staining. Gentisic acid dose-dependently reduced the expression of fibrosis marker genes, suppressed the renin-angiotensin-aldosterone system, and reduced lung size and pulmonary vascular remodeling. Our data indicate that gentisic acid prevents cardiac hypertrophy, fibrosis, cardiac dysfunction, and pulmonary pathology in TAC-induced heart failure. These findings suggest that supplementation with gentisic acid may provide an advantage in preventing the progression from cardiac hypertrophy to heart failure.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publishing date	2019-02-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Class I histone deacetylase inhibitor MS-275 attenuates vasoconstriction and inflammation in angiotensin II-induced hypertension.

Yuhee Ryu / Hae Jin Kee / Simei Sun / Young Mi Seok / Sin Young Choi / Gwi Ran Kim / Seung-Jung Kee / Marc Pflieger / Thomas Kurz / Hyung-Seok Kim / Myung Ho Jeong

PLoS ONE, Vol 14, Iss 3, p e

2019 Volume 0213186

Abstract: OBJECTIVE:Non-selective histone deacetylase (HDAC) inhibitors are known to improve hypertension. Here, we investigated the therapeutic effect and regulatory mechanism of the class I HDAC selective inhibitors, MS-275 and RGFP966, in angiotensin (Ang) II- ... ...

Abstract	OBJECTIVE:Non-selective histone deacetylase (HDAC) inhibitors are known to improve hypertension. Here, we investigated the therapeutic effect and regulatory mechanism of the class I HDAC selective inhibitors, MS-275 and RGFP966, in angiotensin (Ang) II-induced hypertensive mice. METHODS AND RESULTS:MS-275 inhibited the activity of HDAC1, HDAC2, and HDAC3, while RGFP966 weakly inhibited that of HDAC3 in a cell-free system. MS-275 and RGFP966 treatment reduced systolic blood pressure and thickness of the aorta wall in Ang II-induced hypertensive mice. MS-275 treatment reduced aorta collagen deposition, as determined by Masson's trichrome staining. MS-275 decreased the components of the renin angiotensin system and increased vascular relaxation of rat aortic rings via the nitric oxide (NO) pathway. NO levels reduced by Ang II were restored by MS-275 treatment in vascular smooth muscle cells (VSMCs). However, MS-275 dose (3 mg·kg-1·day-1) was not enough to induce NO production in vivo. In addition, MS-275 did not prevent endothelial nitric oxide synthase (eNOS) uncoupling in the aorta of Ang II-induced mice. Treatment with MS-275 failed to inhibit Ang II-induced expression of NADPH oxidase (Nox)1, Nox2, and p47phox. MS-275 treatment reduced proinflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and monocyte chemoattractant protein (MCP)-1, as well as adhesion molecules. Histological analysis showed that Ang II-induced macrophage infiltration was reduced by MS-275 and RGFP966 administration. CONCLUSIONS:Our results indicate that class I HDAC selective inhibitors may be good therapeutic agents for the treatment of hypertension through the regulation of vascular remodeling and vasoconstriction, as well as inflammation.
Keywords	Medicine ; R ; Science ; Q
Subject code	630
Language	English
Publishing date	2019-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Increased level and interferon-γ production of circulating natural killer cells in patients with scrub typhus.

Seung-Ji Kang / Hye-Mi Jin / Young-Nan Cho / Seong Eun Kim / Uh Jin Kim / Kyung-Hwa Park / Hee-Chang Jang / Sook-In Jung / Seung-Jung Kee / Yong-Wook Park

PLoS Neglected Tropical Diseases, Vol 11, Iss 7, p e

2017 Volume 0005815

Abstract: Natural killer (NK) cells are essential immune cells against several pathogens. Not much is known regarding the roll of NK cells in Orientia tsutsugamushi infection. Thus, this study aims to determine the level, function, and clinical relevance of NK ... ...

Abstract	Natural killer (NK) cells are essential immune cells against several pathogens. Not much is known regarding the roll of NK cells in Orientia tsutsugamushi infection. Thus, this study aims to determine the level, function, and clinical relevance of NK cells in patients with scrub typhus.This study enrolled fifty-six scrub typhus patients and 56 health controls (HCs). The patients were divided into subgroups according to their disease severity. A flow cytometry measured NK cell level and function in peripheral blood. Circulating NK cell levels and CD69 expressions were significantly increased in scrub typhus patients. Increased NK cell levels reflected disease severity. In scrub typhus patients, tests showed their NK cells produced higher amounts of interferon (IFN)-γ after stimulation with interleukin (IL)-12 and IL-18 relative to those of HCs. Meanwhile, between scrub typhus patients and HCs, the cytotoxicity and degranulation of NK cells against K562 were comparable. CD69 expressions were recovered to the normal levels in the remission phase.This study shows that circulating NK cells are activated and numerically increased, and they produced more IFN-γ in scrub typhus patients.
Keywords	Arctic medicine. Tropical medicine ; RC955-962 ; Public aspects of medicine ; RA1-1270
Subject code	610
Language	English
Publishing date	2017-07-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Multiplex Real-Time PCR Assay Targeting Eight Parasites Customized to the Korean Population

Eun Jeong Won / Soo Hyun Kim / Seung Jung Kee / Jong Hee Shin / Soon Pal Suh / Jong Yil Chai / Dong Wook Ryang / Myung Geun Shin

PLoS ONE, Vol 11, Iss 11, p e

Potential Use for Detection in Diarrheal Stool Samples from Gastroenteritis Patients.

2016 Volume 0166957

Abstract: Intestinal parasitic diseases occur worldwide and can cause diarrhea or gastroenteritis; however, their diagnosis is quite difficult, especially in low-endemism countries. We developed a multiplex real-time PCR assay for detection of eight intestinal ... ...

Abstract	Intestinal parasitic diseases occur worldwide and can cause diarrhea or gastroenteritis; however, their diagnosis is quite difficult, especially in low-endemism countries. We developed a multiplex real-time PCR assay for detection of eight intestinal parasites and prospectively evaluated it for patients with gastroenteritis. The assay targeted Cryptosporidium parvum, Giardia lamblia, Entamoeba histolytica, Blastocystis hominis, Dientamoeba fragilis, Clonorchis sinensis, Metagonimus yokogawai, and Gymnophalloides seoi. Performance characteristics were evaluated based on recovery after DNA extraction, analytical sensitivity, specificity, reproducibility, cross-reactivity, and interference characteristics. Clinical performance was validated against microscopy on 123 diarrheal samples. The assay demonstrated strong correlations between DNA concentrations and Ct values (R2, 0.9924-0.9998), and had a high PCR efficiency (83.3%-109.5%). Polymerase chain reactions detected as few as 10-30 copies of genomic DNA, and coefficient of variance was 0-7%. There was no cross-reactivity to the other 54 microorganisms tested. Interference occurred only in presence of high concentrations of erythrocytes or leukocytes. This assay had a higher correct identification rate (100.0% vs. 90.2%) and lower incorrect ID rate (0.0% vs. 9.8%) when compared to microscopy. Overall, this assay showed a higher sensitivity (100.0%; 95% confidence interval [CI] of 80.5-100.0) than microscopy (29.4%; 95% CI 10.31-55.96), and the specificity levels were comparable for both methods (100.0%; 95% CI 96.58-100.0). This newly developed multiplex real-time PCR assay offers a potential use for detecting intestinal parasitic pathogens customized to the Korean population.
Keywords	Medicine ; R ; Science ; Q
Subject code	610
Language	English
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Activation, Impaired Tumor Necrosis Factor-α Production, and Deficiency of Circulating Mucosal-Associated Invariant T Cells in Patients with Scrub Typhus.

Seung-Ji Kang / Hye-Mi Jin / Eun Jeong Won / Young-Nan Cho / Hyun-Ju Jung / Yong-Soo Kwon / Hae Jin Kee / Jae Kyun Ju / Jung-Chul Kim / Uh Jin Kim / Hee-Chang Jang / Sook-In Jung / Seung-Jung Kee / Yong-Wook Park

PLoS Neglected Tropical Diseases, Vol 10, Iss 7, p e

2016 Volume 0004832

Abstract: BACKGROUND:Mucosal-associated invariant T (MAIT) cells contribute to protection against certain microorganism infections. However, little is known about the role of MAIT cells in Orientia tsutsugamushi infection. Hence, the aims of this study were to ... ...

Abstract	BACKGROUND:Mucosal-associated invariant T (MAIT) cells contribute to protection against certain microorganism infections. However, little is known about the role of MAIT cells in Orientia tsutsugamushi infection. Hence, the aims of this study were to examine the level and function of MAIT cells in patients with scrub typhus and to evaluate the clinical relevance of MAIT cell levels. METHODOLOGY/PRINCIPAL FINDINGS:Thirty-eight patients with scrub typhus and 53 health control subjects were enrolled in the study. The patients were further divided into subgroups according to disease severity. MAIT cell level and function in the peripheral blood were measured by flow cytometry. Circulating MAIT cell levels were found to be significantly reduced in scrub typhus patients. MAIT cell deficiency reflects a variety of clinical conditions. In particular, MAT cell levels reflect disease severity. MAIT cells in scrub typhus patients displayed impaired tumor necrosis factor (TNF)-α production, which was restored during the remission phase. In addition, the impaired production of TNF-α by MAIT cells was associated with elevated CD69 expression. CONCLUSIONS:This study shows that circulating MAIT cells are activated, numerically deficient, and functionally impaired in TNF-α production in patients with scrub typhus. These abnormalities possibly contribute to immune system dysregulation in scrub typhus infection.
Keywords	Arctic medicine. Tropical medicine ; RC955-962 ; Public aspects of medicine ; RA1-1270
Subject code	610 ; 616
Language	English
Publishing date	2016-07-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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