Publications by authors named "Jinho Kim"

190 Publications

Gender differences in the relationship between perceived discrimination and personality traits in young adulthood: Evidence using sibling fixed effects.

Soc Sci Med 2021 Oct 20;286:114329. Epub 2021 Aug 20.

College of Medicine, Florida State University, Tallahassee, FL, USA.

Rationale: Although perceived discrimination (PD) is known to be associated with personality traits, family background characteristics may confound this association. Moreover, little is known about whether the relationship differs by gender.

Objective: This study investigates whether the association between PD and personality traits is confounded by family background characteristics. Given gender differences in contexts and perceptions of discrimination as well as personality traits, this study also explores whether the association between PD and personality traits differs for men and women.

Methods: Using data from the National Longitudinal Study of Adolescent to Adult Health, this study examines the association between PD and Big Five personality traits among young adults. This study uses sibling fixed effects models with a lagged dependent variable to account for unobservable family-level characteristics, such as genetics, parental characteristics, family environment, and childhood social contexts.

Results: Sibling fixed effects estimates showed that PD was associated with lower levels of conscientiousness and extraversion and higher levels of neuroticism. There were also gender differences such that PD was associated with lower conscientiousness only for women and lower extraversion only for men. The positive association with neuroticism was apparent for both men and women.

Conclusion: This study suggests that the association between PD and personality traits is generally not confounded by stable family-level characteristics shared by siblings. This study also documents gender differences in the relationship between PD and personality traits. Given substantial implications of personality for a broad range of outcomes, especially among young adults, the findings of this study reaffirm the commitment of the whole society to eradicate any form of discrimination.
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http://dx.doi.org/10.1016/j.socscimed.2021.114329DOI Listing
October 2021

In Situ Formation of Ag Nanoparticles for Fiber Strain Sensors: Toward Textile-Based Wearable Applications.

ACS Appl Mater Interfaces 2021 Aug 12;13(33):39868-39879. Epub 2021 Aug 12.

Soft Biomedical Devices Lab, Department of Robotics Engineering, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu-si 42988, Republic of Korea.

Wearable electronic devices have attracted significant attention as important components in several applications. Among various wearable electronic devices, interest in textile electronic devices is increasing because of their high deformability and portability in daily life. To develop textile electronic devices, fiber-based electronic devices should be fundamentally studied. Here, we report a stretchable and sensitive fiber strain sensor fabricated using only harmless materials during an in situ formation process. Despite using a mild and harmless reducing agent instead of typical strong and hazardous reducing agents, the developed fiber strain sensors feature a low initial electrical resistance of 0.9 Ω/cm, a wide strain sensing range (220%), high sensitivity (∼5.8 × 10), negligible hysteresis, and high stability against repeated stretching-releasing deformation (5000 cycles). By applying the fiber sensors to various textiles, we demonstrate that the smart textile system can monitor various gestures in real-time and help users maintain accurate posture during exercise. These results will provide meaningful insights into the development of next-generation wearable applications.
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http://dx.doi.org/10.1021/acsami.1c09879DOI Listing
August 2021

Screening sexual performance enhancing compounds and their analogues in counterfeit and illicit erectile dysfunction drugs by high-performance liquid chromatography and liquid chromatography-tandem mass spectrometry.

J Forensic Leg Med 2021 Aug 28;82:102224. Epub 2021 Jul 28.

Center for Advanced Analysis, National Institute of Food and Drug Safety Evaluation, Ministry of Food and Drug Safety, Osongsaengmyeong 2-ro, Osong-eup, Cheongju-si, Chungcheongbuk-do, 28159, Republic of Korea. Electronic address:

The growth of the counterfeit and illicit drugs market is attributable in part to phosphodiesterase type-5 inhibitor (PDE-5is) medications for erectile dysfunction (ED). PDE-5is and their analogues are being increasingly supplied as counterfeit and illicit drugs marketed to enhance sexual performance. Herein, we screened and confirmed a total of 181 such counterfeit and illicit drugs used to date to enhance sexual performance by high-performance liquid chromatography (HPLC) and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Out of 181 samples, PDE-5is and their analogues were detected in 156 samples, with 49.4% containing two or more components in a single sample. Sildenafil, tadalafil, and miscellaneous group were detected a rates of 64.1%, 34.4%, and 1.5% times and concentrations of 0.04-496 mg/g, 0.02-147 mg/g, and 0.54-16.4 mg/g, respectively with multiple compound groups also detected in single samples. Overdosing on these drugs can lead to adverse effects, the toxicities of combined administrations have not been researched, and administering multiple components in a single sample can be fatal. We recommend that counterfeit and illicit drugs for enhancing sexual performance be continuously controlled and supervised for the protection of public health, and more studies into toxicity and side effects are required.
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http://dx.doi.org/10.1016/j.jflm.2021.102224DOI Listing
August 2021

Expansion of cytotoxic natural killer cells in multiple myeloma patients using K562 cells expressing OX40 ligand and membrane-bound IL-18 and IL-21.

Cancer Immunol Immunother 2021 Jul 20. Epub 2021 Jul 20.

Research Center for Cancer Immunotherapy, Gwangju, South Korea.

Background: Natural killer (NK) cell-based immunotherapy is a promising treatment approach for multiple myeloma (MM), but obtaining a sufficient number of activated NK cells remains challenging. Here, we report an improved method to generate ex vivo expanded NK (eNK) cells from MM patients based on genetic engineering of K562 cells to express OX40 ligand and membrane-bound (mb) IL-18 and IL-21.

Methods: K562-OX40L-mbIL-18/-21 cells were generated by transducing K562-OX40L cells with a lentiviral vector encoding mbIL-18 and mbIL-21, and these were used as feeder cells to expand NK cells from peripheral blood mononuclear cells of healthy donors (HDs) and MM patients in the presence of IL-2/IL-15. Purity, expansion rate, receptor expression, and functions of eNK cells were determined over four weeks of culture.

Results: NK cell expansion was enhanced by short exposure of soluble IL-18 and IL-21 with K562-OX40L cells. Co-culture of NK cells with K562-OX40L-mbIL-18/-21 cells resulted in remarkable expansion of NK cells from HDs (9,860-fold) and MM patients (4,929-fold) over the 28-day culture period. Moreover, eNK cells showed increased expression of major activation markers and enhanced cytotoxicity towards target K562, U266, and RPMI8226 cells.

Conclusions: Our data suggest that genetically engineered K562 cells expressing OX40L, mbIL-18, and mbIL-21 improve the expansion of NK cells, increase activation signals, and enhance their cytolytic activity towards MM cells.
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http://dx.doi.org/10.1007/s00262-021-02982-9DOI Listing
July 2021

Depressive symptoms among cancer patients: Variation by gender, cancer type, and social engagement.

Res Nurs Health 2021 Oct 13;44(5):811-821. Epub 2021 Jul 13.

Department of Health Policy and Management, Korea University, Seoul, Republic of Korea.

Prior literature has documented an association between cancer and depressive symptoms. There has been a limited understanding about whether the association between cancer and depressive symptoms varies by gender and whether social engagement moderates this association. Using seven waves of the Korean Longitudinal Study of Ageing (N = 10,055), we examine the association between cancer and depressive symptoms among middle- and older-aged adults in Korea. We conduct fixed-effects regression models to account for unobserved characteristics of individuals that may confound this association. We first investigate whether the association between cancer and depressive symptom differs by gender. We distinguish among cancer types to assess potentially distinctive mental health consequences of different types of cancer. Then, we explore whether social engagement moderates the cancer-depressive symptoms association. Naive OLS models yielded significant associations between cancer and depressive symptoms for both men and women. However, our preferred fixed effects estimates revealed that the association was statistically significant only for men, and not for women. This association was especially pronounced for lung cancer. We also found that one's level of social engagement including informal connections and formal social activities moderates the link between cancer and depressive symptoms. Cancer is not only a leading cause of death, but also a serious threat to one's mental health. This study sheds light on gender differences in psychological reactions to cancer among Korean adults. Findings of this study hold important implications for programs aiming to improve the mental health and quality of life of cancer patients.
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http://dx.doi.org/10.1002/nur.22168DOI Listing
October 2021

Future expectations of receiving care and all-cause mortality among older adults in Korea.

Health Soc Care Community 2021 Jul 10. Epub 2021 Jul 10.

Department of Health Policy and Management, Korea University, Seoul, Republic of Korea.

While demand for care-giving is increasing rapidly among older adults in Korea, there are large unmet care needs. In the face of an elder care crisis, older adults feel uncertain about how and by whom they will be cared for. This study examines the relationship between expectations of receiving care in the future and all-cause mortality among Korean older adults. We explore whether mortality risk differs by sources of care (non-family vs. family caregivers), and further disaggregate different sources of care by family member type (spouse, sons and daughters). Using data from the Korean Longitudinal Study of Ageing (N = 3,111 participants aged 65 or older), we estimate Cox proportional hazards regression models predicting all-cause mortality. Expecting to receive care from either non-family or family members is significantly associated with lower mortality risk. Expecting care from a spouse and/or daughter was associated with lower mortality risk, but expecting care from sons was not. After adjusting for covariates, expecting future care from a spouse and/or daughter predicted lower mortality risk (HR = 0.83; 95% CI = 0.71-0.97 [spouse], HR = 0.79; 95% CI = 0.67-0.94 [daughter]), and the coefficient for expectations of formal care from non-family members became statistically insignificant. After controlling for family structure, only the association between expecting care from daughters and mortality remained statistically significant (HR = 0.78; 95% CI = 0.66-0.94). These effects are more pronounced among women than men. Initiatives to support and maintain high-quality family relationships across the life course and remove barriers that obstruct family members from providing care to their elders would improve older adults' longevity.
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http://dx.doi.org/10.1111/hsc.13495DOI Listing
July 2021

Sex Difference in Peripheral Inflammatory Biomarkers in Drug-Naïve Patients with Major Depression in Young Adulthood.

Biomedicines 2021 Jun 22;9(7). Epub 2021 Jun 22.

Department of Health Sciences and Technology, GAIHST, Gachon University, Incheon 21936, Korea.

The number of patients with major depressive disorder (MDD) is increasing worldwide. In particular, the early onset of MDD from adolescence to young adulthood is more problematic than the later onset. The specific and expeditious identification of MDD before the occurrence of severe symptoms is significant for future interventions or therapies; however, there is no accurate diagnostic marker that has sufficient sensitivity and specificity for clinical use. In the present study, to identify the possibility of blood markers for depression, we first measured the baseline inflammatory biomarkers in the peripheral blood of 50 treatment-naïve young adults with MDD and 50 matched healthy controls. We then analyzed the correlation between prospective biomarkers and depressive symptoms using scores from various clinical depression indices. We also identified differential responses between males and females in prospective biomarkers. In young adulthood, men with MDD had increased peripheral interleukin (IL)-17 levels, whereas women with MDD had significantly increased IL-1β, IL-6, and C-reactive protein (CRP) levels compared with healthy controls. However, tumor necrosis factor-α (TNF-α), CCL1, CCL2, adiponectin, and cortisol were not significantly different in young adult individuals with MDD. Higher levels of IL-17 in the male group and of IL-1β, IL-6, and CRP in the female group may have been associated with the clinical symptoms of MDD, including depressive moods, hopelessness, suicidal ideation, low self-esteem, and reduced psychological resilience. Our findings will be useful in developing diagnostic tools or treatments for MDD in young adulthood.
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http://dx.doi.org/10.3390/biomedicines9070708DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8301344PMC
June 2021

Geographic variation in Alzheimer's disease mortality.

PLoS One 2021 1;16(7):e0254174. Epub 2021 Jul 1.

Departments of Sociology, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.

Objective: Accumulating evidence suggests the possibility that early life exposures may contribute to risk of Alzheimer's Disease (AD). This paper explores geographic disparities in AD mortality based on both state of residence in older age as well as state of birth measures in order to assess the relative importance of these factors.

Methods: We use a subset of a large survey, the NIH-AARP Diet and Health Study, of over 150,000 individuals aged 65-70 with 15 years of mortality follow-up, allowing us to study over 1050 cases of AD mortality. We use multi-level logistic regression, where individuals are nested within states of residence and/or states of birth, to assess the contributions of place to AD mortality variation.

Results: We show that state of birth explains a modest amount of variation in AD mortality, approximately 4%, which is consistent with life course theories that suggest that early life conditions can produce old age health disparities. However, we also show that nearly all of the variation from state of birth is explained by state of residence in old age.

Conclusions: These results suggest that later life factors are potentially more consequential targets for intervention in reducing AD mortality and provide some evidence against the importance of macro-level environmental exposures at birth as a core determinant of later AD.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0254174PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8248693PMC
July 2021

Association and pathways of birth in the stroke belt on old age dementia and stroke Mortality.

SSM Popul Health 2021 Sep 8;15:100841. Epub 2021 Jun 8.

Department of Sociology, University of Wisconsin-Madison, USA.

This paper uses data from the Diet and Health Study (DHS) to examine associations between being born in a "stroke belt" state and old age stroke and mortality outcomes. Adding to prior work that used administrative data, our paper explores educational and health mechanisms that are both stratified by geography and by mortality outcomes. Using logistic regression, we first replicate earlier findings of elevation in risk of dementia mortality (OR 1.13, CI [1.07, 1.20]) and stroke mortality (OR 1.17, CI [1.07, 1.29]) for white individuals born in a stroke belt state. These associations are largely unaffected by controls for educational attainment or by experiences with surviving a stroke and are somewhat attenuated by controls for self-rated health status in old age. The results suggest a need to consider additional life course mechanisms in order to understand the persistent effects of place of birth on old age mortality patterns.
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http://dx.doi.org/10.1016/j.ssmph.2021.100841DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8233219PMC
September 2021

Homeownership and Psychological Resources Among Older Adults: Do Gender and Mortgage Status Moderate Homeownership Effects?

J Aging Health 2021 Jul 1:8982643211029174. Epub 2021 Jul 1.

34973Korea University, Seoul, Republic of Korea.

This study examined whether homeownership is associated with life satisfaction and depressive symptoms among older adults aged 65 or over and whether these associations differ by gender. This study further distinguished mortgagors from owner-occupiers. Using six waves of the Korean Longitudinal Study of Ageing ( = 3540), we used generalized estimating equations as well as random- and fixed-effects regression analyses. Gender-stratified fixed-effects models showed that the associations between homeownership and psychological resources are largely driven by men. Owner-occupiers are more satisfied with life and report fewer depressive symptoms than renters. By contrast, although mortgagors are more satisfied with life than renters, they have depressive symptoms similar to those of renters. These patterns are more pronounced among men than women. Our findings lend support to policies that promote affordable homeownership as a way to reduce social inequalities in psychological well-being and health, especially among older men.
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http://dx.doi.org/10.1177/08982643211029174DOI Listing
July 2021

Non-destructive vacuum-assisted measurement of lung elastic modulus.

Acta Biomater 2021 09 27;131:370-380. Epub 2021 Jun 27.

Department of Biomedical Engineering, Stevens Institute of Technology, Hoboken, NJ, United States. Electronic address:

In living tissues, mechanical stiffness and biological function are intrinsically linked. Alterations in the stiffness of tissues can induce pathological interactions that affect cellular activity and tissue function. Underlying connections between tissue stiffness and disease highlights the importance of accurate quantitative characterizations of soft tissue mechanics, which can improve our understanding of disease and inform therapeutic development. In particular, accurate measurement of lung mechanical properties has been especially challenging due to the anatomical and mechanobiological complexities of the lung. Discrepancies between measured mechanical properties of dissected lung tissue samples and intact lung tissues in vivo has limited the ability to accurately characterize integral lung mechanics. Here, we report a non-destructive vacuum-assisted method to evaluate mechanical properties of soft biomaterials, including intact tissues and hydrogels. Using this approach, we measured elastic moduli of rat lung tissue that varied depending on stress-strain distribution throughout the lung. We also observed that the elastic moduli of enzymatically disrupted lung parenchyma increased by at least 64%. The reported methodology enables assessment of the nonlinear viscoelastic characteristics of intact lungs under normal and abnormal (i.e., injured, diseased) conditions and allows measurement of mechanical properties of tissue-mimetic biomaterials for use in therapeutics or in vitro models. STATEMENT OF SIGNIFICANCE: Accurate quantification of tissue stiffness is critical for understanding mechanisms of disease and developing effective therapeutics. Current modalities to measure tissue stiffness are destructive and preclude accurate assessment of lung mechanical properties, as lung mechanics are determined by complex features of the intact lung. To address the need for alternative methods to assess lung mechanics, we report a non-destructive vacuum-based approach to quantify tissue stiffness. We applied this method to correlate lung tissue mechanics with tissue disruption, and to assess the stiffness of biomaterials. This method can be used to inform the development of tissue-mimetic materials for use in therapeutics and disease models, and could potentially be applied for in-situ evaluation of tissue stiffness as a diagnostic or prognostic tool.
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http://dx.doi.org/10.1016/j.actbio.2021.06.037DOI Listing
September 2021

Longitudinal Associations Between Expectations of Receiving Care in the Future and Life Satisfaction Among Older Adults in Korea.

J Gerontol B Psychol Sci Soc Sci 2021 Jun 30. Epub 2021 Jun 30.

Department of Health Policy and Management, Korea University, Seoul, Republic of Korea.

Objectives: Uncertainty about receiving care and assistance in the future has been increasing among older adults in Korea. This study examines whether expectations about receiving care from various sources (i.e., formal and/or filial caregivers) are related to life satisfaction among older adults in Korea.

Methods: Using data from the Korean Longitudinal Study of Ageing (N = 3,607, aged 65 or older), this study estimated fixed effects regression models to investigate longitudinal within-person associations between future care expectations and life satisfaction.

Results: The results of this study revealed that developing expectations of care from family caregivers is positively associated with life satisfaction. Beginning to expect care from non-family caregivers, however, is not associated with life satisfaction. When disaggregating different sources of care by family member type, expecting care from a spouse or daughter(s), but not son(s), is associated with higher life satisfaction. Gender-specific analyses showed that expecting care from daughter(s) is positively associated with life satisfaction among both men and women, whereas expectations of spousal care are associated with only men's life satisfaction. This study also found suggestive but not conclusive evidence that an association between care expectations from family caregivers and life satisfaction is stronger among older adults with lower education.

Discussion: Reducing uncertainty about future care may improve older adults' subjective well-being. Policymakers may consider policies and programs that support family care of the aged, and more fundamentally, encourage family involvement in the lives of older people.
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http://dx.doi.org/10.1093/geronb/gbab121DOI Listing
June 2021

Interaction of genetic and environmental factors for body fat mass control: observational study for lifestyle modification and genotyping.

Sci Rep 2021 Jun 23;11(1):13180. Epub 2021 Jun 23.

Samsung Genome Institute, Samsung Medical Center, Sungkyunkwan University, Ilwon-ro 81, Gangnam-gu, Seoul, 06351, South Korea.

Previous studies suggested that genetic, environmental factors and their interactions could affect body fat mass (BFM). However, studies describing these effects were performed at a single time point in a population. In this study, we investigated the interaction between genetic and environmental factors in affecting BFM and implicate the healthcare utilization of lifestyle modifications from a personalized and genomic perspective. We examined how nutritional intake or physical activity changes in the individuals affect BFM concerning the genetic composition. We conducted an observational study including 259 adult participants with single nucleotide polymorphism (SNP) genotyping and longitudinal lifestyle monitoring, including food consumption and physical activities, by following lifestyle modification guidance. The participants' lifelog data on exercise and diet were collected through a wearable device for 3 months. Moreover, we measured anthropometric and serologic markers to monitor their potential changes through lifestyle modification. We examined the influence of genetic composition on body fat reduction induced by lifestyle changes using genetic risk scores (GRSs) of three phenotypes: GRS-carbohydrate (GRS-C), GRS-fat (GRS-F), and GRS-exercise (GRS-E). Our results showed that lifestyle modifications affected BFM more significantly in the high GRS class compared to the low GRS class, indicating the role of genetic factors affecting the efficiency of the lifestyle modification-induced BFM changes. Interestingly, the influence of exercise modification in the low GRS class with active lifestyle change was lower than that in the high GRS class with inactive lifestyle change (P = 0.022), suggesting the implication of genetic factors for efficient body fat control.
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http://dx.doi.org/10.1038/s41598-021-92229-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8222320PMC
June 2021

Personality, health behaviours and physical health in young adulthood.

Authors:
Jinho Kim

Psychol Health 2021 Jun 16:1-20. Epub 2021 Jun 16.

Department of Health Policy and Management, Korea University, Seoul, Republic of Korea.

Objective: Personality traits and health are strongly correlated, but unobserved family-level characteristics may confound this relationship. This study investigates whether associations between personality traits and physical health are spurious owing to unobserved family background.

Design: Participants were from the National Longitudinal Study of Adolescent to Adult Health. This study employed sibling fixed-effect approach to account for unobserved family characteristics.

Main Outcome Measures: Main dependent variables were Framingham Risk Scores for 30-year full cardiovascular disease (CVD) and metabolic syndrome.

Results: Sibling fixed-effects models showed that conscientiousness is associated with reductions in CVD risk and metabolic syndrome, and that neuroticism is associated with an increase in both conditions. A higher extraversion score is positively associated with CVD risk. The adverse effect of extraversion on CVD risk is larger among females, and the protective effect of conscientiousness is larger among males. Moreover, while extraversion, neuroticism and conscientiousness are associated with health behaviours in somewhat distinct ways, the associations for agreeableness and openness are spurious owing to unobserved family background.

Conclusion: This study ruled out the concern that unobserved family background drives the personality-physical health link. Mechanisms linking personality to physical health may be gendered.
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http://dx.doi.org/10.1080/08870446.2021.1934468DOI Listing
June 2021

The Relationship Between Children's Gender Composition and Parents' All-Cause Mortality Among Older Adults in Korea.

Authors:
Jinho Kim

J Appl Gerontol 2021 May 19:7334648211012122. Epub 2021 May 19.

Korea University, Seoul, Republic of Korea.

Using data from the Korean Longitudinal Study of Aging ( = 3,356 participants aged 65 or older) and estimating Cox proportional hazard regression models, this study investigated the association between gender composition of children and parents' mortality risk. This study showed that compared with having both daughters and sons, having exclusively daughters (but not exclusively sons) was associated with higher mortality risk. This association, however, was significant for mothers, but not for fathers. To shed light on source of this association, this study distinguished between mothers with only daughters who receive and do not receive regular financial support from children. Results showed that mothers had elevated mortality risk only if they do not receive regular financial support from their children. Traditional caregiving roles of sons for older parents in Korea may lead to a mortality disadvantage among mothers of daughters vis-à-vis a reduction in financial assistance from children.
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http://dx.doi.org/10.1177/07334648211012122DOI Listing
May 2021

The Role of Violent and Nonviolent Delinquent Behavior in Educational Attainment.

Authors:
Jinho Kim

Youth Soc 2020 Apr 14;52(3):377-402. Epub 2018 Jun 14.

Department of Sociology, University of Wisconsin-Madison, 1180 Observatory Drive, Madison, WI 53706.

Given large variations in the etiology and developmental trajectories of violent and nonviolent delinquency, this study examines whether educational outcomes of violent and nonviolent offenders might differ. In particular, this study attempts to remove environmental influences such as family background and neighborhood effects from the effects of delinquency because these factors are likely to differentially confound the effects of violent and nonviolent delinquency on educational attainment. By exploiting variation within sibling pairs, this study finds that the effects of engagement in violent delinquency on education is driven spuriously by shared family background, whereas the effects of nonviolent delinquency are quite robust to adjustment for family fixed effects. Moreover, relying on fixed effects estimates, this study finds that the effects of engagement in nonviolent delinquent activity on educational attainment occur in part through disruption of educational progress, rather than through institutional responses to student delinquency and social-psychological processes.
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http://dx.doi.org/10.1177/0044118x18781641DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8075283PMC
April 2020

Transcriptomic profiling of three-dimensional cholangiocyte spheroids long term exposed to repetitive Clonorchis sinensis excretory-secretory products.

Parasit Vectors 2021 Apr 20;14(1):213. Epub 2021 Apr 20.

Department of Convergence Medicine, University of Ulsan College of Medicine and Asan Institute for Life Sciences, Asan Medical Center, Seoul, 05505, Republic of Korea.

Background: Biliary tract infection with the carcinogenic human liver fluke, Clonorchis sinensis, provokes chronic inflammation, epithelial hyperplasia, periductal fibrosis, and even cholangiocarcinoma. Complications are proportional to the intensity and duration of the infection. In addition to mechanical irritation of the biliary epithelia from worms, their excretory-secretory products (ESPs) cause chemical irritation, which leads to inflammation, proliferation, and free radical generation.

Methods: A three-dimensional in vitro cholangiocyte spheroid culture model was established, followed by ESP treatment. This allowed us to examine the intrinsic pathological mechanisms of clonorchiasis via the imitation of prolonged and repetitive in vivo infection.

Results: Microarray and RNA-Seq analysis revealed that ESP-treated cholangiocyte H69 spheroids displayed global changes in gene expression compared to untreated spheroids. In ESP-treated H69 spheroids, 185 and 63 probes were found to be significantly upregulated and downregulated, respectively, corresponding to 209 genes (p < 0.01, fold change > 2). RNA-Seq was performed for the validation of the microarray results, and the gene expression patterns in both transcriptome platforms were well matched for 209 significant genes. Gene ontology analysis demonstrated that differentially expressed genes were mainly classified into immune system processes, the extracellular region, and the extracellular matrix. Among the upregulated genes, four genes (XAF1, TRIM22, CXCL10, and BST2) were selected for confirmation using quantitative RT-PCR, resulting in 100% similar expression patterns in microarray and RNA-Seq.

Conclusions: These findings broaden our understanding of the pathological pathways of liver fluke-associated hepatobiliary disorders and suggest a novel therapeutic strategy for this infectious cancer.
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http://dx.doi.org/10.1186/s13071-021-04717-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8056535PMC
April 2021

The complete mitochondrial genome of (Clupeiformes: Clupeidae).

Mitochondrial DNA B Resour 2021 Mar 24;6(3):1178-1180. Epub 2021 Mar 24.

Department of Life Science & Biotechnology, Soonchunhyang University, Asan, Republic of Korea.

The complete mitogenome of was determined by next-generation sequencing. The . mitogenome was a circular 16,307 bp molecule that contained 13 protein-coding genes, 22 tRNA genes, 2 rRNA genes, and one control region (D-loop). The gene arrangement was consistent with other mitogenomes. The phylogenetic relationships of 29 Clupeoidei species based on 13 protein-coding genes from the available mitogenomes were analyzed. clustered with among Clupeidae, suggesting a closer relationship with this genus. These results will be useful for understanding the phylogenetic relationships, taxonomic classification, and phylogeography of the genus relative to other genera of Clupeoidei.
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http://dx.doi.org/10.1080/23802359.2021.1902407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7995902PMC
March 2021

Complete mitochondrial DNA sequence of Norwegian skates ( Lafont, 1871) imported to Korea.

Mitochondrial DNA B Resour 2021 Mar 15;6(3):865-867. Epub 2021 Mar 15.

Department of Life Science & Biotechnology, Soonchunhyang University, Asan, Republic of Korea.

In this study, the complete mitochondrial genome of Norwegian skates imported to Korea was sequenced with a circular molecule of 17,121 bp, which consisted of 13 protein-coding genes (PCGs), 2 ribosomal RNAs, 22 transfer RNA genes, and a control region (D-loop). And among these sequences, 193 bp sequence in the D-loop of the genus suggested the possibility of being used as a genetic marker for classification of and species. The BI phylogenetic tree by using the nucleotide sequences of 13 PCGs from 15 available mitogenomes of family Rajidae confirmed also that Norwegian skates imported to Korea form a group with species with high branch value, and that this was a species of . As above, these results would be expected to provide for the further understanding on the phylogenetic relationship, taxonomic classification and phylogeography of the family Rajidae.
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http://dx.doi.org/10.1080/23802359.2021.1886003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7971281PMC
March 2021

Transcriptome Analysis Reveals HgCl Induces Apoptotic Cell Death in Human Lung Carcinoma H1299 Cells through Caspase-3-Independent Pathway.

Int J Mol Sci 2021 Feb 18;22(4). Epub 2021 Feb 18.

Department of Life Science, Chung-Ang University, Seoul 06974, Korea.

Mercury is one of the detrimental toxicants that can be found in the environment and exists naturally in different forms; inorganic and organic. Human exposure to inorganic mercury, such as mercury chloride, occurs through air pollution, absorption of food or water, and personal care products. This study aimed to investigate the effect of HgCl on cell viability, cell cycle, apoptotic pathway, and alters of the transcriptome profiles in human non-small cell lung cancer cells, H1299. Our data show that HgCl treatment causes inhibition of cell growth via cell cycle arrest at G/G- and S-phase. In addition, HgCl induces apoptotic cell death through the caspase-3-independent pathway. Comprehensive transcriptome analysis using RNA-seq indicated that cellular nitrogen compound metabolic process, cellular metabolism, and translation for biological processes-related gene sets were significantly up- and downregulated by HgCl treatment. Interestingly, comparative gene expression patterns by RNA-seq indicated that mitochondrial ribosomal proteins were markedly altered by low-dose of HgCl treatment. Altogether, these data show that HgCl induces apoptotic cell death through the dysfunction of mitochondria.
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http://dx.doi.org/10.3390/ijms22042006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7922270PMC
February 2021

Bisphenol A Exposure Changes the Transcriptomic and Proteomic Dynamics of Human Retinoblastoma Y79 Cells.

Genes (Basel) 2021 02 11;12(2). Epub 2021 Feb 11.

Department of Life Science, Chung-Ang University, Seoul 06974, Korea.

Bisphenol A (BPA) is a xenoestrogen chemical commonly used to manufacture polycarbonate plastics and epoxy resin and might affect various human organs. However, the cellular effects of BPA on the eyes have not been widely investigated. This study aimed to investigate the cellular cytotoxicity by BPA exposure on human retinoblastoma cells. BPA did not show cytotoxic effects, such as apoptosis, alterations to cell viability and cell cycle regulation. Comparative analysis of the transcriptome and proteome profiles were investigated after long-term exposure of Y79 cells to low doses of BPA. Transcriptome analysis using RNA-seq revealed that mRNA expression of the post-transcriptional regulation-associated gene sets was significantly upregulated in the BPA-treated group. Cell cycle regulation-associated gene sets were significantly downregulated by exposure to BPA. Interestingly, RNA-seq analysis at the transcript level indicated that alternative splicing events, particularly retained introns, were noticeably altered by low-dose BPA treatment. Additionally, proteome profiling using MALDI-TOF-MS identified a total of nine differentially expressed proteins. These results suggest that alternative splicing events and altered gene/protein expression patterns are critical phenomena affected by long-term low-dose BPA exposure. This represents a novel marker for the detection of various diseases associated with environmental pollutants such as BPA.
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http://dx.doi.org/10.3390/genes12020264DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7918513PMC
February 2021

Multifunctional Microparticles with Stimulation and Sensing Capabilities for Facile NK Cell Activity Assay.

ACS Sens 2021 03 19;6(3):693-697. Epub 2021 Feb 19.

Research Institute of Advanced Materials (RIAM), Seoul National University, Seoul, 08826, South Korea.

Natural killer (NK) cells are a subset of innate lymphoid cells playing an important role in immune surveillance and early defense against infection and cancer. They recognize and directly kill infected or transformed cells. At the same time, they produce various cytokines and chemokines to regulate other immune cells. NK cell activity can be a useful marker for health screenings because impaired NK cell functions may indicate a more susceptible environment for infection or tumor development. Currently, most NK cell activity assays are focused on measuring either cytokine secretion, in particular, interferon γ (IFN-γ), or cytotoxicity against target cells such as K562, thus only providing partial information on NK cell activity. In order to develop a comprehensive test for measuring NK cell function, cytotoxicity and cytokine secretion ability should be measured simultaneously. In addition, current NK cell assays are performed by stimulating NK cells with cocktails of cytokines, antibody-coated beads, or live target cells. In this study, we developed multifunctional microparticles for NK cell activity assay (MNAs) that allow simultaneous stimulation and sensing various NK cell activities, including cytokine secretion and cytotoxicity. The surfaces of MNAs are decorated with multiple functional biomolecules, including antibodies that stimulate NK cells by engaging NK cell activating receptors, antibodies that can capture cytokines secreted by NK cells, and a peptide sensor that reacts with granzyme B, a key molecule released by NK cells for cytotoxicity. The performances of MNAs are assessed using flow cytometry and live cell imaging. NK cell activity is measured by simply mixing MNAs with NK cells and performing flow cytometry, and the results are comparable to those measured by standard NK cell activity assays.
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http://dx.doi.org/10.1021/acssensors.0c02138DOI Listing
March 2021

Engineering Saccharomyces cerevisiae for isoprenol production.

Metab Eng 2021 03 10;64:154-166. Epub 2021 Feb 10.

Joint BioEnergy Institute, 5885 Hollis Street, Emeryville, CA 94608, USA; Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA. Electronic address:

Isoprenol (3-methyl-3-butene-1-ol) is a valuable drop-in biofuel and an important precursor of several commodity chemicals. Synthetic microbial systems using the heterologous mevalonate pathway have recently been developed for the production of isoprenol in Escherichia coli, and a significant yield and titer improvement has been achieved through a decade of research. Saccharomyces cerevisiae has been widely used in the biotechnology industry for isoprenoid production, but there has been no good example of isoprenol production reported in this host. In this study, we engineered the budding yeast S. cerevisiae for improved biosynthesis of isoprenol. The strain engineered with the mevalonate pathway achieved isoprenol production at the titer of 36.02 ± 0.92 mg/L in the flask. The IPP (isopentenyl diphosphate)-bypass pathway, which has shown more efficient isoprenol production by avoiding the accumulation of the toxic intermediate in E. coli, was also constructed in S. cerevisiae and improved the isoprenol titer by 2-fold. We further engineered the strains by deleting a promiscuous endogenous kinase that could divert the pathway flux away from the isoprenol production and improved the titer to 130.52 ± 8.01 mg/L. Finally, we identified a pathway bottleneck using metabolomics analysis and overexpressed a promiscuous alkaline phosphatase to relieve this bottleneck. The combined efforts resulted in the titer improvement to 383.1 ± 31.62 mg/L in the flask. This is the highest isoprenol titer up to date in S. cerevisiae and this work provides the key strategies to engineer yeast as an industrial platform for isoprenol production.
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http://dx.doi.org/10.1016/j.ymben.2021.02.002DOI Listing
March 2021

Spatial memory deficiency early in 6xTg Alzheimer's disease mouse model.

Sci Rep 2021 01 14;11(1):1334. Epub 2021 Jan 14.

Department of Pharmacology, College of Medicine, Gachon University, Incheon, 21999, Republic of Korea.

Alzheimer's disease (AD) is mainly characterized by the deposition of extracellular amyloid plaques and intracellular accumulation of neurofibrillary tangles (NFTs). While the recent 5xFAD AD mouse model exhibits many AD-related phenotypes and a relatively early and aggressive amyloid β production, it does not show NFTs. Here, we developed and evaluated a novel AD mouse model (6xTg-AD, 6xTg) by crossbreeding 5xFAD mice with mice expressing mutant (P301L) tau protein (MAPT). Through behavioral and histopathological tests, we analyzed cognitive changes and neuropathology in 6xTg mice compared to their respective parental strains according to age. Spatial memory deficits occurred in 6xTg mice at 2 months of age, earlier than they occurred in 5xFAD mice. Histopathological data revealed aggressive Aβ42 and p-tau accumulation in 6xTg mice. Microglial activation occurred in the cortex and hippocampus of 6xTg mice beginning at 2 months. In 6xTg model mice, the synaptic loss was observed in the cortex from 4 months of age and in the hippocampus from 6 months of age, and neuronal loss appeared in the cortex from 4 months of age and in the hippocampus 6 months of age, earlier than it is observed in the 5xFAD and JNPL3 models. These results showed that each pathological symptom appeared much faster than in their parental animal models. In conclusion, these novel 6xTg-AD mice might be an advanced animal model for studying AD, representing a promising approach to developing effective therapy.
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http://dx.doi.org/10.1038/s41598-020-79344-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809274PMC
January 2021

Interleukin-17 induced by cumulative mild stress promoted depression-like behaviors in young adult mice.

Mol Brain 2021 01 13;14(1):11. Epub 2021 Jan 13.

Department of Health Sciences and Technology, GAIHST, Gachon University, Incheon, 21936, Korea.

The number of young adult patients with major depression, one of the most common mental disorders, is gradually increasing in modern society. Stressful experiences in early life are considered one of the risk factors for chronic depressive symptoms, along with an abnormal inflammatory response in later life. Although increased inflammatory activity has been identified in patients with depression, the cause of long-lasting depressive states is still unclear. To identify the effects of cumulative mild stress in brain development periods, we generated a young adult depression mouse model exposed to cumulative mild stress (CPMS; cumulative mild prenatal stress, mild maternal separation, and mild social defeat) to mimic early life adversities. CPMS mice exhibited more long-lasting anxiety and depression-like behaviors than groups exposed to single or double combinations of mild stress in young adult age. Using the molecular works, we found that inflammatory cytokines, especially interleukin (IL)-17, upregulated microglial activation in the hippocampus, amygdala, and prefrontal cortex of CPMS mice. In the brains of CPMS mice, we also identified changes in the T helper (Th)-17 cell population as well as differentiation. Finally, anti-IL-17 treatment rescued anxiety and depression-like behavior in CPMS mice. In conclusion, we found that cumulative mild stress promoted long-lasting depressive symptoms in CPMS mice through the upregulation of IL-17. We suggest that the CPMS model may be useful to study young adult depression and expect that IL-17 may be an important therapeutic target for depression in young adults.
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http://dx.doi.org/10.1186/s13041-020-00726-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7805143PMC
January 2021

A disposable smart microfluidic platform integrated with on-chip flow sensors.

Biosens Bioelectron 2021 Mar 16;176:112897. Epub 2020 Dec 16.

Department of Nanoscience and Engineering, Center for Nano Manufacturing, Inje University, Gimhae-si, 50834, South Korea. Electronic address:

Microfluidic devices are powerful tools for biological, biomedical, chemical, and pharmaceutical applications, but their commercialization is still hindered by the lack of methods to automatically control fluid flow in a low-cost, simple, accurate, and safe manner. This study introduces a disposable smart microfluidic platform (DIS-μChip), which can be fully automated and utilized for a wide range of applications. On-chip microfluidic flow sensors are integrated with the platform and placed at all inlet and outlet channels, thereby allowing the DIS-μChip to be fully automated with a pressure control system. Furthermore, these confer a self-diagnosis function through monitoring of all the input and output flow rates. The DIS-μChip consists of a disposable polymeric microchannel superstrate and a permanent multifunctional substrate, which could be assembled and disassembled using only vacuum pressure. The superstrate was fabricated by combining a polydimethylsiloxane microchannel structure with a polyethylene terephthalate (PET) thin film. The substrate contains sense electrodes for the on-chip-integrated flow sensors and functional components for creating an energy field, which can penetrate the PET thin film and manipulate the fluid in the microchannels of the superstrate. Owing to the film-chip technique, the superstrate was disposable and could prevent biological cross-contamination, which cannot be realized with conventional flow sensors. The usefulness of the DIS-μChip was demonstrated by using it to isolate circulating tumor cells from the blood of patients with pancreatic cancer and to obtain cancer-specific genetic information from them with droplet digital PCR.
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http://dx.doi.org/10.1016/j.bios.2020.112897DOI Listing
March 2021

Analysis of total corneal astigmatism with a rotating Scheimpflug camera in keratoconus.

BMC Ophthalmol 2020 Dec 3;20(1):475. Epub 2020 Dec 3.

Department of Ophthalmology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea.

Background: To analyze mean corneal powers and astigmatisms on anterior, posterior, and total cornea in patients with keratoconus as calculated according to various keratometric measurements using a Scheimpflug camera.

Methods: We examined the left eyes of 64 patients (41 males and 23 females; mean age 29.94 ± 6.63 years) with keratoconus. We measured simulated K (Sim-K), posterior K, true net power (TNP) and four types of total corneal refractive powers (TCRP). We then used the obtained values to analyze mean K, and corneal astigmatism. TCRP were measured at 2.0 ~ 5.0 mm.

Results: Mean corneal powers from Sim K, posterior K, and TNP were 49.12 ± 3.99, - 7.39 ± 0.79, and 47.78 ± 4.09 diopters, respectively. For TCRP centered on the pupil, mean K tended to decrease with measurement area (all p < 0.01). While, both mean K and astigmatism measured using TCRP centered on the apex decreased with measurement area (all p < 0.001). TCRP centered on the apex were greater than those centered on the pupil for mean K values calculated using TCRP (all p < 0.001). The proportion of WTR was greatest on the anterior and total cornea. As the measurement area moved to the periphery, the proportion of WTR increased.

Conclusions: Mean corneal powers and astigmatisms on total cornea with keratoconus change depending on calculation methods and measurement areas.
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http://dx.doi.org/10.1186/s12886-020-01747-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7713345PMC
December 2020

Chemotherapy induces dynamic immune responses in breast cancers that impact treatment outcome.

Nat Commun 2020 12 2;11(1):6175. Epub 2020 Dec 2.

Oncology Research & Development, Pfizer, San Diego, CA, USA.

To elucidate the effects of neoadjuvant chemotherapy (NAC), we conduct whole transcriptome profiling coupled with histopathology analyses of a longitudinal breast cancer cohort of 146 patients including 110 pairs of serial tumor biopsies collected before treatment, after the first cycle of treatment and at the time of surgery. Here, we show that cytotoxic chemotherapies induce dynamic changes in the tumor immune microenvironment that vary by subtype and pathologic response. Just one cycle of treatment induces an immune stimulatory microenvironment harboring more tumor infiltrating lymphocytes (TILs) and up-regulation of inflammatory signatures predictive of response to anti-PD1 therapies while residual tumors are immune suppressed at end-of-treatment compared to the baseline. Increases in TILs and CD8+ T cell proportions in response to NAC are independently associated with pathologic complete response. Further, on-treatment immune response is more predictive of treatment outcome than immune features in paired baseline samples although these are strongly correlated.
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http://dx.doi.org/10.1038/s41467-020-19933-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710739PMC
December 2020

Multigene model for predicting metastatic prostate cancer using circulating tumor cells by microfluidic magnetophoresis.

Cancer Sci 2021 Feb 11;112(2):859-870. Epub 2020 Dec 11.

Department of Nanoscience and Engineering Center for Nano Manufacturing, Inje University, Gimhae, South Korea.

We aimed to isolate circulating tumor cells (CTCs) using a microfluidic technique with a novel lateral magnetophoretic microseparator. Prostate cancer-specific gene expressions were evaluated using mRNA from the isolated CTCs. A CTC-based multigene model was then developed for identifying advanced prostate cancer. Peripheral blood samples were obtained from five healthy donors and patients with localized prostate cancer (26 cases), metastatic hormone-sensitive prostate cancer (mHSPC, 10 cases), and metastatic castration-resistant prostate cancer (mCRPC, 28 cases). CTC recovery rate and purity (enriched CTCs/total cells) were evaluated according to cancer stage. The areas under the curves of the six gene expressions were used to evaluate whether multigene models could identify mHSPC or mCRPC. The number of CTCs and their purity increased at more advanced cancer stages. In mHSPC/mCRPC cases, the specimens had an average of 27.5 CTCs/mL blood, which was 4.2 × higher than the isolation rate for localized disease. The CTC purity increased from 2.1% for localized disease to 3.8% for mHSPC and 6.7% for mCRPC, with increased CTC expression of the genes encoding prostate-specific antigen (PSA), prostate-specific membrane antigen (PSMA), and cytokeratin 19 (KRT19). All disease stages exhibited expression of the genes encoding androgen receptor (AR) and epithelial cell adhesion molecule (EpCAM), although expression of the AR-V7 variant was relatively rare. Relative to each gene alone, the multigene model had better accuracy for predicting advanced prostate cancer. Our lateral magnetophoretic microseparator can be used for identifying prostate cancer biomarkers. In addition, CTC-based genetic signatures may guide the early diagnosis of advanced prostate cancer.
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http://dx.doi.org/10.1111/cas.14745DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7893993PMC
February 2021
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