Publications by authors named "Jieun Song"

52 Publications

Verbal Ability, Behavior Problems, and Mother-Child Relationship Quality in Autism Spectrum Disorder.

J Autism Dev Disord 2021 Jun 15. Epub 2021 Jun 15.

Waisman Center, University of Wisconsin-Madison, Madison, USA.

This study examined differences in mother-child relationship quality and parent-rated child behavior problems based on child verbal status (i.e., minimally verbal versus verbal) in mothers and their adolescent and adult children with autism spectrum disorder (n = 219 dyads; child M = 25.38 years, SD = 10.22). Relationship quality was assessed via parent-reported maternal burden and mother-child closeness, and coded speech samples ascertaining maternal critical and positive remarks regarding the child. Groups did not differ in relationship quality. The verbal group was more likely to display disruptive and socially inappropriate behaviors, but otherwise the groups did not differ in behavior problems. Verbal status moderated the relationship between behavior problems and negative (maternal burden, critical remarks) but not positive (mother-child closeness, positive remarks) aspects of relationship quality.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10803-021-05133-2DOI Listing
June 2021

Who Returns? Understanding Varieties of Longitudinal Participation in MIDUS.

J Aging Health 2021 May 17:8982643211018552. Epub 2021 May 17.

5228University of Wisconsin-Madison, Madison, WI, USA.

This study describes a major effort to reinstate dropouts from the MIDUS longitudinal study and compare baseline characteristics among subgroups of participants to better understand predictors of retention, attrition, and reinstatement. All living dropouts were contacted, and 651 reinstated participants were interviewed in person (31.4% response rate). Age, gender, education, marital status, parental status, and physical and mental health were compared among the following groups: longitudinal sample, reinstated sample, those fielded for reinstatement who did not return, and those who dropped out at the 2nd or 3rd wave. Multivariate analyses revealed that reinstated participants were younger, male, unmarried, and less educated and had children at baseline compared to longitudinal participants. Reinstatement was unsuccessful among those with poorer mental health at baseline compared to longitudinal participants. This study informs reinstatement efforts, adjustment for attrition bias, and use of to examine aging consequents of early life vulnerability.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/08982643211018552DOI Listing
May 2021

The role of prosodic and visual information in disambiguating wh-indeterminates: The case of Korean three-year-olds.

J Child Lang 2021 Mar 25:1-23. Epub 2021 Mar 25.

Department of Speech, Hearing & Phonetic Sciences, University College London, UK.

In Korean language, questions containing ambiguous wh-words may be interpreted as either wh-questions or yes-no questions. This study investigated 43 Korean three-year-olds' ability to disambiguate eight indeterminate questions using prosodic and visual cues. The intonation of each question provided a cue as to whether it should be interpreted as a wh-question or a yes-no question. The questions were presented alongside picture stimuli, which acted as either a matched (presentation of corresponding auditory-visual stimuli) or a mismatched contextual cue (presentation conflicting auditory-visual stimuli). Like adults, the children preferred to comprehend questions involving ambiguous wh-words as wh-questions, rather than yes-no questions. In addition, children were as effective as adults in disambiguating indeterminate questions using prosodic cues regardless of the visual cue. However, when confronted with conflicting auditory-visual stimuli (mismatched), the quality of children's responses was less accurate than adults' responses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1017/S0305000921000143DOI Listing
March 2021

Opioid Literacy of Korean Americans in Rural Alabama: Addressing the Role of Social Determinants of Health.

J Transcult Nurs 2021 Feb 20:1043659621995902. Epub 2021 Feb 20.

Pusan Catholic University, Geumjeong-gu, Busan, South Korea.

Introduction: Opioid crisis has disproportionately affected Alabamians with the highest opioid prescription rate, and it is subjected to affect Korean Americans (KA) negatively based on common predictors of opioid misuse that KA possess.

Method: Cross-sectional data of KA in rural Alabama ( = 230) were analyzed. Opioid literacy was assessed by the Brief Opioid Overdose Knowledge survey. Six social determinants of health factors were considered: financial status, educational attainment, English proficiency, household food insecurity, health literacy, and social contact.

Results: Participants had limited opioid literacy ( = 3.56, = 3.06). After adjusting for demographics and health covariates, higher levels of overall opioid literacy were associated with higher household income ( = .48, < .01), higher levels of health literacy ( = .71, < .01), and less frequent social contact ( = -.40, < .01). Significant social determinants of health predictors varied across subdomains of opioid literacy.

Discussion: The findings suggest that culturally competent and community-level interventions are needed to increase opioid literacy in KA in rural Alabama.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1043659621995902DOI Listing
February 2021

Potent antitumor effects of cell-penetrating peptides targeting STAT3 axis.

JCI Insight 2021 01 25;6(2). Epub 2021 Jan 25.

Department of Immuno-Oncology and.

To date, there are no inhibitors that directly and specifically target activated STAT3 and c-Myc in the clinic. Although peptide-based inhibitors can selectively block activated targets, their clinical usage is limited because of low cell penetration and/or serum stability. Here, we generated cell-penetrating acetylated (acet.) STAT3, c-Myc, and Gp130 targeting peptides by attaching phosphorothioated (PS) polymer backbone to peptides. The cell-penetrating peptides efficiently penetrated cells and inhibited activation of the intended targets and their downstream genes. Locally or systemically treating tumor-bearing mice with PS-acet.-STAT3 peptide at low concentrations effectively blocked STAT3 in vivo, resulting in significant antitumor effects in 2 human xenograft models. Moreover, PS-acet.-STAT3 peptide penetrated and activated splenic CD8+ T cells in vitro. Treating immune-competent mice bearing mouse melanoma with PS-acet.-STAT3 peptide inhibited STAT3 in tumor-infiltrating T cells, downregulating tumor-infiltrating CD4+ T regulatory cells while activating CD8+ T effector cells. Similarly, systemic injections of the cell-penetrating c-Myc and Gp130 peptides prevented pancreatic tumor growth and induced antitumor immune responses. Taken together, we have developed therapeutic peptides that effectively and specifically block challenging cancer targets, resulting in antitumor effects through both direct tumor cell killing and indirectly through antitumor immune responses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1172/jci.insight.136176DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934871PMC
January 2021

Auditory neural tracking and lexical processing of speech in noise: Masker type, spatial location, and language experience.

J Acoust Soc Am 2020 07;148(1):253

Department of Speech, Hearing and Phonetic Sciences, University College London, Chandler House, 2 Wakefield Street, London, WC1N 1PF, United Kingdom.

The present study investigated how single-talker and babble maskers affect auditory and lexical processing during native (L1) and non-native (L2) speech recognition. Electroencephalogram (EEG) recordings were made while L1 and L2 (Korean) English speakers listened to sentences in the presence of single-talker and babble maskers that were colocated or spatially separated from the target. The predictability of the sentences was manipulated to measure lexical-semantic processing (N400), and selective auditory processing of the target was assessed using neural tracking measures. The results demonstrate that intelligible single-talker maskers cause listeners to attend more to the semantic content of the targets (i.e., greater context-related N400 changes) than when targets are in babble, and that listeners track the acoustics of the target less accurately with single-talker maskers. L1 and L2 listeners both modulated their processing in this way, although L2 listeners had more difficulty with the materials overall (i.e., lower behavioral accuracy, less context-related N400 variation, more listening effort). The results demonstrate that auditory and lexical processing can be simultaneously assessed within a naturalistic speech listening task, and listeners can adjust lexical processing to more strongly track the meaning of a sentence in order to help ignore competing lexical content.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1121/10.0001477DOI Listing
July 2020

Association between Bone Mineral Density and Serum Iron Indices in Premenopausal Women in South Korea.

Korean J Fam Med 2020 May 20;41(3):175-182. Epub 2020 May 20.

Department of Family Medicine, Kyungpook National University Hospital, Daegu, Korea.

Background: Osteoporosis is characterized by a decrease in bone mineral density (BMD) and increased risk of fragility fractures. Serum iron level may interact with bone health status. This study investigated the correlations of BMD with serum iron level, hemoglobin level, and total iron-binding capacity (TIBC).

Methods: We performed a retrospective analysis of data from the medical records of premenopausal women in South Korea. The women's BMDs and the Z scores of the BMDs were verified using dual-energy X-ray absorption. The participants were stratified into quartiles for analyses of the associations of BMD with serum iron level, TIBC, and hemoglobin level.

Results: A simple linear regression analysis revealed associations of changes in BMD with iron level (β=-0.001, standard error [SE]=0.001, P<0.001), hemoglobin level (β=0.015, SE=0.003, P<0.001), and TIBC (β=0.001, SE=0.001, P<0.001). This pattern was also observed in a multiple linear regression analysis. A multivariate logistic regression analysis of iron level and TIBC for low BMD revealed odds ratios of 1.005 (P<0.001) and 0.995 (P<0.001), respectively.

Conclusion: This study demonstrated clear relationships of changes in BMD with serum iron level and TIBC, and thus confirms the usefulness of these markers in the clinical evaluation of iron storage and BMD in younger women.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4082/kjfm.18.0142DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7272370PMC
May 2020

Apolipoprotein ɛ4 Allele and Subjective Cognitive Functioning in Parents of Adults With Disabilities.

J Gerontol B Psychol Sci Soc Sci 2020 09;75(8):e189-e197

Waisman Center, University of Wisconsin-Madison.

Objectives: Parents of individuals with disabilities face ongoing responsibilities of providing care and support for their children, even during the child's adulthood. Past research has shown that this caregiving role is linked to chronic stress and subsequent adverse health outcomes for parents, including impaired cognition. This study examines the impacts of genetic risk for cognitive impairment (apolipoprotein [APOE] ɛ4 allele) among parents of adults with disabilities and comparison parents whose adult children do not have disabilities.

Method: We performed rank order regression analysis of data from the Wisconsin Longitudinal Study (2004-2006 and 2010-2012 surveys and DNA samples). Participants included parents of adults with disabilities (247 mothers and 159 fathers) and comparison parents whose adult children were not disabled (1,482 mothers and 954 fathers).

Results: Mothers who had adult children with disabilities and who were APOE ɛ4 carriers reported significantly declining levels of subjective cognitive functioning over time, but mothers of adults with disabilities who did not have the APOE ɛ4 allele did not manifest this change. Among comparison group mothers, cognitive change over time was not a function of their APOE ɛ4 carrier status. Fathers' cognitive function did not differ significantly by either parental status or APOE ɛ4 carrier status.

Discussion: The results show that older mothers of adults with disabilities are more susceptible to cognitive impairment than their age peers if they have the genetic risk factor of APOE ɛ4 allele.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/geronb/gbaa061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7489093PMC
September 2020

Integrin α6 signaling induces STAT3-TET3-mediated hydroxymethylation of genes critical for maintenance of glioma stem cells.

Oncogene 2020 03 9;39(10):2156-2169. Epub 2019 Dec 9.

Department of Immuno-Oncology, Beckman Research Institute at City of Hope Comprehensive Cancer Center, Duarte, CA, 91010, USA.

Both the extracellular matrix (ECM) and DNA epigenetic regulation are critical for maintaining stem cell phenotype and cancer progression. Whether and how ECM regulates epigenetic alterations to influence cancer stem cells (CSCs) remain to be explored. Here we report that ECM through laminin-integrin α6 upregulates ten-eleven translocation enzyme 3 (TET3) dioxygenase. TET3 in turn mediates DNA cytosine 5'-hydroxymethylation (5hmC) and upregulates genes critical for maintenance of glioma stem cells (GSCs). Activating integrin α6-FAK pathway increases STAT3 activity, TET3 expression and 5hmC levels in GSCs. Moreover, targeting STAT3 disrupts integrin α6-FAK signaling and inhibits TET3 GSC maturation in vivo. STAT3 directly regulates TET3 expression and the two proteins are co-localized with 5hmC in GSC clusters. 5hmC is upregulated by STAT3 at the promoters of several tumorigenic genes, including c-Myc, known to be critical for GSCs. In vivo silencing of TET3 in GSC-enriched tumors reduces 5hmC accumulation and expression of the GSC critical genes, leading to tumor growth inhibition. TET3 expression and 5hmC accumulation also co-segregate with integrin α6 in patient malignant glioma. Thus, ECM- integrin α6-STAT3-TET3 axis regulates hydroxymethylation of genes important for GSCs, thereby increasing GSC tumorigenicity and resistance to therapies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41388-019-1134-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7060098PMC
March 2020

STAT3 Activation-Induced Fatty Acid Oxidation in CD8 T Effector Cells Is Critical for Obesity-Promoted Breast Tumor Growth.

Cell Metab 2020 01 21;31(1):148-161.e5. Epub 2019 Nov 21.

Department of Immuno-Oncology, City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA. Electronic address:

Although obesity is known to be critical for cancer development, how obesity negatively impacts antitumor immune responses remains largely unknown. Here, we show that increased fatty acid oxidation (FAO) driven by activated STAT3 in CD8 T effector cells is critical for obesity-associated breast tumor progression. Ablating T cell Stat3 or treatment with an FAO inhibitor in obese mice spontaneously developing breast tumor reduces FAO, increases glycolysis and CD8 T effector cell functions, leading to inhibition of breast tumor development. Moreover, PD-1 ligation in CD8 T cells activates STAT3 to increase FAO, inhibiting CD8 T effector cell glycolysis and functions. Finally, leptin enriched in mammary adipocytes and fat tissues downregulates CD8 T cell effector functions through activating STAT3-FAO and inhibiting glycolysis. We identify a critical role of increased oxidation of fatty acids driven by leptin and PD-1 through STAT3 in inhibiting CD8 T effector cell glycolysis and in promoting obesity-associated breast tumorigenesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cmet.2019.10.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6949402PMC
January 2020

Activation of sonic hedgehog signaling by a Smoothened agonist restores congenital defects in mouse models of endocrine-cerebro-osteodysplasia syndrome.

EBioMedicine 2019 Nov 26;49:305-317. Epub 2019 Oct 26.

Department of Anatomy, Yonsei University College of Medicine, Seoul 03722, Korea; Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul 03722, Korea; BK21 PLUS project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Korea; Severance Biomedical Science Institute, Yonsei University College of Medicine, Seoul 03722, Korea. Electronic address:

Background: Endocrine-cerebro-osteodysplasia (ECO) syndrome is a genetic disorder associated with congenital defects of the endocrine, cerebral, and skeletal systems in humans. ECO syndrome is caused by mutations of the intestinal cell kinase (ICK) gene, which encodes a mitogen-activated protein (MAP) kinase-related kinase that plays a critical role in controlling the length of primary cilia. Lack of ICK function disrupts transduction of sonic hedgehog (SHH) signaling, which is important for development and homeostasis in humans and mice. Craniofacial structure abnormalities, such as cleft palate, are one of the most common defects observed in ECO syndrome patients, but the role of ICK in palatal development has not been studied.

Methods: Using Ick-mutant mice, we investigated the mechanisms by which ICK function loss causes cleft palate and examined pharmacological rescue of the congenital defects.

Findings: SHH signaling was compromised with abnormally elongated primary cilia in the developing palate of Ick-mutant mice. Cell proliferation was significantly decreased, resulting in failure of palatal outgrowth, although palatal adhesion and fusion occurred normally. We thus attempted to rescue the congenital palatal defects of Ick mutants by pharmacological activation of SHH signaling. Treatment of Ick-mutant mice with an agonist for Smoothened (SAG) rescued several congenital defects, including cleft palate.

Interpretations: The recovery of congenital defects by pharmacological intervention in the mouse models for ECO syndrome highlights prenatal SHH signaling modulation as a potential therapeutic measure to overcome congenital defects of ciliopathies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ebiom.2019.10.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6945271PMC
November 2019

Mortality in parents after the death of a child.

Soc Sci Med 2019 10 28;239:112522. Epub 2019 Aug 28.

Department of Psychology, University of Hawaii at Manoa, USA. Electronic address:

Objective: The death of a child is a traumatic stressor that takes a toll on the health of parents. This study examined long-term impacts of the death of a child on the risk of early mortality in bereaved parents. In a follow-up analysis, a twin subsample was analyzed to examine potential genetic confounding.

Method: We analyzed data from the Midlife in the United States (MIDUS) study. The primary sample consists of two groups of MIDUS 2 participants (2004-06); (1) parents who experienced the death of a child prior to MIDUS 2 (n = 451) and (2) comparison parents who had not experienced death of any children (n = 1804) (mean age = 63). We also analyzed 52 twin pairs in which one twin experienced the death of a child and 271 twin pairs in which both twins had all living children. Mortality status of parents was assessed in 2017.

Results: Parents who had experienced the death of a child had a 32% higher likelihood of early mortality (defined as dying earlier than life expectancy) than their peers who did not have any deceased children, and they were more likely to die of heart disease. Analyses of the twin subsample revealed significantly lower concordance for early mortality among the pairs with a bereaved twin than among control twins, consistent with non-genetic effects.

Conclusions: The findings suggest that the death of a child has lasting impacts on the risk of early mortality in bereaved parents. This study provides the first U.S. estimate of bereavement effects on mortality extending through the parents' full life course, with significant public health implications. In addition, analysis of concordance of early death rates in the twin subsample suggests the impact on mortality of parental bereavement, net of genetic factors.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.socscimed.2019.112522DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6802289PMC
October 2019

Fibroblast growth factor receptor influences primary cilium length through an interaction with intestinal cell kinase.

Proc Natl Acad Sci U S A 2019 03 19;116(10):4316-4325. Epub 2019 Feb 19.

Department of Biology, Faculty of Medicine, Masaryk University, 62500 Brno, Czech Republic;

Vertebrate primary cilium is a Hedgehog signaling center but the extent of its involvement in other signaling systems is less well understood. This report delineates a mechanism by which fibroblast growth factor (FGF) controls primary cilia. Employing proteomic approaches to characterize proteins associated with the FGF-receptor, FGFR3, we identified the serine/threonine kinase intestinal cell kinase (ICK) as an FGFR interactor. ICK is involved in ciliogenesis and participates in control of ciliary length. FGF signaling partially abolished ICK's kinase activity, through FGFR-mediated ICK phosphorylation at conserved residue Tyr15, which interfered with optimal ATP binding. Activation of the FGF signaling pathway affected both primary cilia length and function in a manner consistent with cilia effects caused by inhibition of ICK activity. Moreover, knockdown and knockout of ICK rescued the FGF-mediated effect on cilia. We provide conclusive evidence that FGF signaling controls cilia via interaction with ICK.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1073/pnas.1800338116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6410813PMC
March 2019

miRNA-mediated TUSC3 deficiency enhances UPR and ERAD to promote metastatic potential of NSCLC.

Nat Commun 2018 11 30;9(1):5110. Epub 2018 Nov 30.

Comprehensive Cancer Center, The Ohio State University, Columbus, OH, 43210, USA.

Non-small cell lung carcinoma (NSCLC) is leading cause of cancer-related deaths in the world. The Tumor Suppressor Candidate 3 (TUSC3) at chromosome 8p22 known to be frequently deleted in cancer is often found to be deleted in advanced stage of solid tumors. However, the role of TUSC3 still remains controversial in lung cancer and context-dependent in several cancers. Here we propose that miR-224/-520c-dependent TUSC3 deficiency enhances the metastatic potential of NSCLC through the alteration of three unfolded protein response pathways and HRD1-dependent ERAD. ATF6α-dependent UPR is enhanced whereas the affinity of HRD1 to its substrates, PERK, IRE1α and p53 is weakened. Consequently, the alteration of UPRs and the suppressed p53-NM23H1/2 pathway by TUSC3 deficiency is ultimately responsible for enhancing metastatic potential of lung cancer. These findings provide mechanistic insight of unrecognized roles of TUSC3 in cancer progression and the oncogenic role of HRD1-dependent ERAD in cancer metastasis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-018-07561-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6269493PMC
November 2018

Health of parents of individuals with developmental disorders or mental health problems: Impacts of stigma.

Soc Sci Med 2018 11 15;217:152-158. Epub 2018 Oct 15.

School of Social Work and Waisman Center, University of Wisconsin-Madison, Madison, USA. Electronic address:

Objective: Parents of individuals with developmental disorders or mental health problems often provide life-long care and support to their children, which negatively affects their health in part due to chronic stress. This study aimed to examine the experience of stigma as a source of chronic stress among parents of individuals with developmental disorders or mental health problems and the effect of stigma on parental health outcomes.

Method: Using data from the Survey of Midlife in the United States (MIDUS 2 and 3), we constructed a sample for a longitudinal analysis including 128 parents of individuals with developmental disorders (e.g., autism, cerebral palsy, epilepsy, Down syndrome, intellectual disabilities, brain injury, ADD/ADHD) or mental health problems (e.g., bipolar disorder, schizophrenia, major depression) and 2256 parents whose children were nondisabled.

Results: Parents who had children with developmental disorders or mental health problems prior to the beginning of the study (i.e., at MIDUS 1) reported higher levels of stigma related to embarrassment/shame and daily discrimination than parents of nondisabled individuals ten years later at MIDUS 2, which in turn were associated with poorer parental health outcomes (poorer self-rated health and a greater number of chronic conditions) nearly a decade after that at MIDUS 3.

Conclusions: The findings suggest that the stigma associated with parenting a child with disabilities may be one mechanism that places such parents at risk for poor health. Efforts to alleviate the stigma associated with developmental disorders or mental health problems may have beneficial effects on health of parents of individuals with such conditions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.socscimed.2018.09.044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6202233PMC
November 2018

Listening effort during speech perception enhances auditory and lexical processing for non-native listeners and accents.

Cognition 2018 10 26;179:163-170. Epub 2018 Jun 26.

Department of Speech, Hearing and Phonetic Sciences, University College London, Chandler House, 2 Wakefield Street, London WC1N 1PF, United Kingdom.

Speech communication in a non-native language (L2) can feel effortful, and the present study suggests that this effort affects both auditory and lexical processing. EEG recordings (electroencephalography) were made from native English (L1) and Korean listeners while they listened to English sentences spoken with two accents (English and Korean) in the presence of a distracting talker. Neural entrainment (i.e., phase locking between the EEG recording and the speech amplitude envelope) was measured for target and distractor talkers. L2 listeners had relatively greater entrainment for target talkers than did L1 listeners, likely because their difficulty with L2 speech recognition caused them to focus more attention on the speech signal. N400 was measured for the final word in each sentence, and L2 listeners had greater lexical processing in high-predictability sentences than did L1 listeners. L1 listeners had greater target-talker entrainment when listening to the more difficult L2 accent than their own L1 accent, and similarly had larger N400 responses for the L2 accent. It thus appears that the increased effort of L2 listeners, as well as L1 listeners understanding L2 speech, modulates their auditory and lexical processing during speech recognition. This may provide a mechanism to compensate for their perceptual challenges under adverse conditions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cognition.2018.06.001DOI Listing
October 2018

JAK/STAT3-Regulated Fatty Acid β-Oxidation Is Critical for Breast Cancer Stem Cell Self-Renewal and Chemoresistance.

Cell Metab 2018 01 14;27(1):136-150.e5. Epub 2017 Dec 14.

Department of Immuno-Oncology, Beckman Research Institute and City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA. Electronic address:

Cancer stem cells (CSCs) are critical for cancer progression and chemoresistance. How lipid metabolism regulates CSCs and chemoresistance remains elusive. Here, we demonstrate that JAK/STAT3 regulates lipid metabolism, which promotes breast CSCs (BCSCs) and cancer chemoresistance. Inhibiting JAK/STAT3 blocks BCSC self-renewal and expression of diverse lipid metabolic genes, including carnitine palmitoyltransferase 1B (CPT1B), which encodes the critical enzyme for fatty acid β-oxidation (FAO). Moreover, mammary-adipocyte-derived leptin upregulates STAT3-induced CPT1B expression and FAO activity in BCSCs. Human breast-cancer-derived data suggest that the STAT3-CPT1B-FAO pathway promotes cancer cell stemness and chemoresistance. Blocking FAO and/or leptin re-sensitizes them to chemotherapy and inhibits BCSCs in mouse breast tumors in vivo. We identify a critical pathway for BCSC maintenance and breast cancer chemoresistance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cmet.2017.11.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5777338PMC
January 2018

Electrocatalytic Conversion of Carbon Dioxide and Nitrate Ions to Urea by a Titania-Nafion Composite Electrode.

ChemSusChem 2017 10 19;10(20):3999-4003. Epub 2017 Sep 19.

Department of Chemistry and Korea Center for Artificial Photosynthesis, Sogang University, Seoul, 121-742, Korea.

CO and nitrate ions were successfully converted to urea by a TiO -Nafion nanocomposite electrode under ambient conditions. The composite electrode was constructed by dropcasting the mixture of P25 titania and Nafion solution on an indium-doped tin oxide (ITO) electrode. When the electrode was electrolyzed in CO -saturated 0.1 m KNO (pH 4.5) solution at -0.98 V versus Ag/AgCl, urea was formed with a Faradaic efficiency of 40 %. The other reduced products obtained were NH , CO, and H .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cssc.201701448DOI Listing
October 2017

Mangosteen Extract Prevents Dextran Sulfate Sodium-Induced Colitis in Mice by Suppressing NF-κB Activation and Inflammation.

J Med Food 2017 Aug 27;20(8):727-733. Epub 2017 Jun 27.

College of Pharmacy and Integrated Research Institute for Drug Development, Dongguk University-Seoul , Goyang, South Korea .

In this study, the anti-inflammatory effects of mangosteen extract (MGE) on dextran sulfate sodium (DSS)-induced colitis in mice and nuclear factor (NF)-κB pathway modulation were investigated. Acute colitis was induced by administering 3% DSS in drinking water for 7 days, and three groups of Institute of Cancer Research mice were treated with 30 and 120 mg/kg MGE or 5-aminosalicylic acid for 7 days; an additional two groups of mice served as healthy and disease controls. The results indicated that MGE significantly prevented weight loss, reduced disease activity index scores, and preserved colon length compared with the findings in the untreated colitis group. MGE downregulated the NF-κB pathway by inhibiting the phosphorylation of IκB and IKK in a dose-dependent manner. These findings suggest that MGE alleviates ulcerative colitis by modulating the NF-κB pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/jmf.2017.3944DOI Listing
August 2017

α-Mangostin ameliorates dextran sulfate sodium-induced colitis through inhibition of NF-κB and MAPK pathways.

Int Immunopharmacol 2017 Aug 7;49:212-221. Epub 2017 Jun 7.

College of Pharmacy, Integrated Research Institute for Drug Development, Dongguk University-Seoul, 32 Dongguk-lo, Ilsandong-gu, Goyang-si, Gyeonggi-do 10326, Republic of Korea. Electronic address:

Ulcerative colitis (UC) is a chronic inflammatory bowel disease (IBD) of the colon as a target site. Previous reports regarding the efficacy of α-mangostin (αMG) to inhibit nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs) as well as relatively high distribution to the colon suggested the therapeutic potential of this compound in UC model. In dextran sodium sulfate (DSS)-induced colitis mice (DSS mice), the disease activity index scores involving diarrhea, bloody stool, body weight reduction, and myeloperoxidase (MPO) activities of the esophagus and colon increased with the reduced colon length. Also histologic disturbances and changes of NF-κB and MAPK pathways including phosphorylation of IκB kinase, ERK1/2, SAPK/JNK and p38 were observed in the colon of the DSS mice. However, all of these impaired conditions in the DSS mice were restored by αMG treatment, and the intestinal metabolism of αMG decreased, increasing its distribution to the colons in the DSS mice compared with the control mice. All of these results suggest that high distribution of αMG in the colon might attenuate DSS-induced colitis by inhibiting NF-κB and MAPK pathways in the colon.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.intimp.2017.05.040DOI Listing
August 2017

Vaccinia-related kinase 3 (VRK3) sets the circadian period and amplitude by affecting the subcellular localization of clock proteins in mammalian cells.

Biochem Biophys Res Commun 2017 05 13;487(2):320-326. Epub 2017 Apr 13.

Neuroscience Graduate Program, Department of Biomedical Sciences, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-gu, Suwon, Kyunggi-do, 16499, Republic of Korea; Department of Brain Science, Ajou University School of Medicine, 164 Worldcup-ro, Yeongtong-gu, Suwon, Kyunggi-do, 16499, Republic of Korea. Electronic address:

In the eukaryotic circadian clock machinery, negative feedback repression of CLOCK (CLK) and BMAL1 transcriptional activity by PERIOD (PER) and CRYPTOCHROME (CRY) underlies the basis for 24 h rhythmic gene expression. Thus, precise regulation of the time-dependent nuclear entry of circadian repressors is crucial to generating normal circadian rhythms. Here, we sought to identify novel kinase(s) that regulate nuclear entry of mammalian CRY1 (mCRY1) with an unbiased screening using red fluorescent protein (RFP)-tagged human kinome expression plasmids in mammalian cells. Transient expression of human vaccinia-related kinase 3 (hVRK3) reduced the nuclear presence of mCRY1. hVRK3 expression also induced alterations in the subcellular localization of other core clock proteins, including mCRY2, mPER2, and BMAL1. In contrast, the subcellular localization of mCLK was not changed. Given that singly expressed mCLK mostly resides in the cytoplasm and that nuclear localization sequence (NLS) mutation of hVRK3 attenuated the effect of hVRK3 co-expression on subcellular localization, ectopically expressed hVRK3 presumably reduces the retention of proteins in the nucleus. Finally, downregulation of hvrk3 using siRNA reduced the amplitude and lengthened the period of the cellular bioluminescence rhythm. Taken together, these data suggest that VRK3 plays a role in setting the amplitude and period length of circadian rhythms in mammalian cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbrc.2017.04.057DOI Listing
May 2017

The Impact of the Great Recession on Midlife and Older parents of Individuals With a Mental Health Problem or a Developmental Disability.

Gerontologist 2018 05;58(3):448-455

School of Social Work and Waisman Center, University of Wisconsin-Madison.

Background And Objectives: Parents of sons and daughters with disabilities have ongoing financial burdens and vulnerability due to the demands of caregiving responsibilities and their related direct and indirect costs. This study aims to investigate whether midlife and older parents of individuals with a mental health problem or a developmental disability were particularly vulnerable to the impact of the recession.

Research Design And Methods: The data were drawn from Midlife in the United States (MIDUS), a longitudinal survey of a national probability sample in the United States, Waves II (2004-2006) and III (2013-2014; 84 parents of individuals with a mental health problem, 98 parents of individuals with a developmental disability, and 2,029 parents of individuals without any conditions as a comparison group).

Results: The findings suggest that the midlife and older parents whose son or daughter had a mental health problem experienced more recession impacts than comparison parents, even after controlling prerecession financial status and sociodemographic characteristics.

Discussion And Implications: The results indicate the need for policies that provide effective financial support and reduce restrictions on health service access in order to relieve the financial burden experienced by midlife and older parents of individuals with a mental health problem.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/geront/gnw269DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5946810PMC
May 2018

An inactivating mutation in intestinal cell kinase, ICK, impairs hedgehog signalling and causes short rib-polydactyly syndrome.

Hum Mol Genet 2016 09 27;25(18):3998-4011. Epub 2016 Jul 27.

Department of Biology, Faculty of Medicine, Masaryk University, 62500 Brno, Czech Republic.

The short rib polydactyly syndromes (SRPS) are a group of recessively inherited, perinatal-lethal skeletal disorders primarily characterized by short ribs, shortened long bones, varying types of polydactyly and concomitant visceral abnormalities. Mutations in several genes affecting cilia function cause SRPS, revealing a role for cilia function in skeletal development. To identify additional SRPS genes and discover novel ciliary molecules required for normal skeletogenesis, we performed exome sequencing in a cohort of patients and identified homozygosity for a missense mutation, p.E80K, in Intestinal Cell Kinase, ICK, in one SRPS family. The p.E80K mutation abolished serine/threonine kinase activity, resulting in altered ICK subcellular and ciliary localization, increased cilia length, aberrant cartilage growth plate structure, defective Hedgehog and altered ERK signalling. These data identify ICK as an SRPS-associated gene and reveal that abnormalities in signalling pathways contribute to defective skeletogenesis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/hmg/ddw240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5291234PMC
September 2016

Sulforaphene Interferes with Human Breast Cancer Cell Migration and Invasion through Inhibition of Hedgehog Signaling.

J Agric Food Chem 2016 Jul 29;64(27):5515-24. Epub 2016 Jun 29.

Department of Food Science and Technology, Chung-Ang University , Anseong, 456-756, South Korea.

Although inhibition of mammary tumorigenesis by isothiocyanates has been widely studied, little is known about the effects of sulforaphene on invasiveness of breast cancer. Here, sulforaphene significantly inhibited the migration and invasion of triple-negative SUM159 human breast cancer cells and suppressed the expression and activity of matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9). The Hedgehog (Hh) pathway, as an upstream signaling modulator, was significantly suppressed by sulforaphene. In particular, ciliary localization of Gli1 and its nuclear translocation were blocked by sulforaphene in a time-dependent manner. Consistently, downregulation of Hh signaling by vismodegib and Gli1 knockdown reduced the cellular migration and invasion as well as the expression of MMP-2 and MMP-9. These results indicate that the suppression of Hh/Gli1 signaling by sulforaphene may reduce the MMP-2 and MMP-9 activities and cellular invasiveness of human breast cancer cells, suggesting the potential efficacy of sulforaphene against breast cancer invasion and metastasis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.jafc.6b02195DOI Listing
July 2016

Primary cilia in energy balance signaling and metabolic disorder.

BMB Rep 2015 Dec;48(12):647-54

College of Pharmacy, Dongguk University, Goyang 10326, Korea.

Energy homeostasis in our body system is maintained by balancing the intake and expenditure of energy. Excessive accumulation of fat by disrupting the balance system causes overweight and obesity, which are increasingly becoming global health concerns. Understanding the pathogenesis of obesity focused on studying the genes related to familial types of obesity. Recently, a rare human genetic disorder, ciliopathy, links the role for genes regulating structure and function of a cellular organelle, the primary cilium, to metabolic disorder, obesity and type II diabetes. Primary cilia are microtubule based hair-like membranous structures, lacking motility and functions such as sensing the environmental cues, and transducing extracellular signals within the cells. Interestingly, the subclass of ciliopathies, such as Bardet-Biedle and Alström syndrome, manifest obesity and type II diabetes in human and mouse model systems. Moreover, studies on genetic mouse model system indicate that more ciliary genes affect energy homeostasis through multiple regulatory steps such as central and peripheral actions of leptin and insulin. In this review, we discuss the latest findings in primary cilia and metabolic disorders, and propose the possible interaction between primary cilia and the leptin and insulin signal pathways which might enhance our understanding of the unambiguous link of a cell's antenna to obesity and type II diabetes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4791320PMC
http://dx.doi.org/10.5483/bmbrep.2015.48.12.229DOI Listing
December 2015

The Relative Risk of Divorce in Parents of Children With Developmental Disabilities: Impacts of Lifelong Parenting.

Am J Intellect Dev Disabil 2015 Nov;120(6):514-26

and Frank J. Floyd, University of Hawaii at Manoa.

We prospectively examined the risk of divorce in 190 parents of children with developmental disabilities compared to 7,251 parents of children without disabilities based on a random sample drawn from the community and followed longitudinally for over 50 years. A significant interaction between the parental group status and number of children was found: In the comparison group, having a larger number of children was related to an increased risk of divorce, whereas the number of children did not increase divorce risk among parents of children with developmental disabilities.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1352/1944-7558-120.6.514DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4624231PMC
November 2015

Cognitive Aging in Parents of Children with Disabilities.

J Gerontol B Psychol Sci Soc Sci 2016 09 24;71(5):821-30. Epub 2015 Mar 24.

Department of Psychology, Brandeis University, Waltham, Massachusetts.

Objective: This study examines the cognitive functioning of parents of children with disabilities, specifically, whether there is an evidence of accelerated cognitive aging among these parents. In addition, the study investigates the moderating influences of two variables: parents' gender and stress from negative parenting experience.

Method: The analyses utilize data from the National Survey of Midlife in the United States (2005). The analytic sample consisted of two groups of parents, who completed the cognitive battery, the interview, and the mail-back survey: 128 parents who had children with childhood-onset disabilities and 512 matched comparison parents who had only nondisabled children.

Results: Age differences in episodic memory were more pronounced among mothers of children with disabilities than among mothers with nondisabled children, especially among mothers with higher levels of negative parenting experience. In contrast, there were no interaction effects of parenting status, age, and negative parenting experience among fathers.

Discussion: The results show that parenting children with disabilities over a prolonged period of time jeopardizes cognitive function (especially memory) among older mothers, possibly via the mechanism of heightened parenting stress due to higher levels of negative parenting experience.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/geronb/gbv015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4982381PMC
September 2016

Piperlongumine treatment inactivates peroxiredoxin 4, exacerbates endoplasmic reticulum stress, and preferentially kills high-grade glioma cells.

Neuro Oncol 2014 Oct 30;16(10):1354-64. Epub 2014 May 30.

Dardinger Neuro-oncology Center, Department of Neurological Surgery, Ohio State University, Columbus, Ohio (T.H.K., J.S., S.-H.K., A.K.P., I.N., B.K., C.-H.K.); Solid Tumor Program at the James Comprehensive Cancer Center, Columbus, Ohio (T.H.K., J.S., A.K.P., C.-H.K.); Center for Biostatistics, Ohio State University, Columbus, Ohio (X.M.); Department of Radiation Oncology, Ohio State University, Columbus, Ohio (K.P.); Division of Hematology, Department of Internal Medicine, Ohio State University, Columbus, Ohio (J.Y.); Department of Molecular and Cellular Biochemistry, Ohio State University Wexner Medical Center, Columbus, Ohio (S.O.Y.).

Backgrounds: Piperlongumine, a natural plant product, kills multiple cancer types with little effect on normal cells. Piperlongumine raises intracellular levels of reactive oxygen species (ROS), a phenomenon that may underlie the cancer-cell killing. Although these findings suggest that piperlongumine could be useful for treating cancers, the mechanism by which the drug selectively kills cancer cells remains unknown.

Methods: We treated multiple high-grade glioma (HGG) sphere cultures with piperlongumine and assessed its effects on ROS and cell-growth levels as well as changes in downstream signaling. We also examined the levels of putative piperlongumine targets and their roles in HGG cell growth.

Results: Piperlongumine treatment increased ROS levels and preferentially killed HGG cells with little effect in normal brain cells. Piperlongumine reportedly increases ROS levels after interactions with several redox regulators. We found that HGG cells expressed higher levels of the putative piperlongumine targets than did normal neural stem cells (NSCs). Furthermore, piperlongumine treatment in HGG cells, but not in normal NSCs, increased oxidative inactivation of peroxiredoxin 4 (PRDX4), an ROS-reducing enzyme that is overexpressed in HGGs and facilitates proper protein folding in the endoplasmic reticulum (ER). Moreover, piperlongumine exacerbated intracellular ER stress, an effect that was mimicked by suppressing PRDX4 expression.

Conclusions: Our results reveal that the mechanism by which piperlongumine preferentially kills HGG cells involves PRDX4 inactivation, thereby inducing ER stress. Therefore, piperlongumine treatment could be considered as a novel therapeutic option for HGG treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/neuonc/nou088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4165421PMC
October 2014

Intestinal cell kinase, a protein associated with endocrine-cerebro-osteodysplasia syndrome, is a key regulator of cilia length and Hedgehog signaling.

Proc Natl Acad Sci U S A 2014 Jun 22;111(23):8541-6. Epub 2014 May 22.

College of Pharmacy, Dongguk University-Seoul, Goyang, 410-820, Korea;

Endocrine-cerebro-osteodysplasia (ECO) syndrome is a recessive genetic disorder associated with multiple congenital defects in endocrine, cerebral, and skeletal systems that is caused by a missense mutation in the mitogen-activated protein kinase-like intestinal cell kinase (ICK) gene. In algae and invertebrates, ICK homologs are involved in flagellar formation and ciliogenesis, respectively. However, it is not clear whether this role of ICK is conserved in mammals and how a lack of functional ICK results in the characteristic phenotypes of human ECO syndrome. Here, we generated Ick knockout mice to elucidate the precise role of ICK in mammalian development and to examine the pathological mechanisms of ECO syndrome. Ick null mouse embryos displayed cleft palate, hydrocephalus, polydactyly, and delayed skeletal development, closely resembling ECO syndrome phenotypes. In cultured cells, down-regulation of Ick or overexpression of kinase-dead or ECO syndrome mutant ICK resulted in an elongation of primary cilia and abnormal Sonic hedgehog (Shh) signaling. Wild-type ICK proteins were generally localized in the proximal region of cilia near the basal bodies, whereas kinase-dead ICK mutant proteins accumulated in the distal part of bulged ciliary tips. Consistent with these observations in cultured cells, Ick knockout mouse embryos displayed elongated cilia and reduced Shh signaling during limb digit patterning. Taken together, these results indicate that ICK plays a crucial role in controlling ciliary length and that ciliary defects caused by a lack of functional ICK leads to abnormal Shh signaling, resulting in congenital disorders such as ECO syndrome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1073/pnas.1323161111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4060650PMC
June 2014
-->