Low-level brain somatic mutations in exonic regions are collectively implicated in autism with germline mutations in autism risk genes

Kim Il Bin,Kim Myeong-Heui,Jung Saehoon,Kim Woo Kyeong,Lee Junehawk,Ju Young Seok,Webster Maree J.,Kim Sanghyeon,Kim Ja Hye,Kim Hyun Jung,Kim Junho,Kim Sangwoo,Lee Jeong Ho 생화학분자생물학회 2024 Experimental and molecular medicine Vol.56 No.-

Low-level somatic mutations in the human brain are implicated in various neurological disorders. The contribution of low-level brain somatic mutations to autism spectrum disorder (ASD), however, remains poorly understood. Here, we performed high-depth exome sequencing with an average read depth of 559.3x in 181 cortical, cerebellar, and peripheral tissue samples to identify brain somatic single nucleotide variants (SNVs) in 24 ASD subjects and 31 controls. We detected ~2.4 brain somatic SNVs per exome per single brain region, with a variant allele frequency (VAF) as low as 0.3%. The mutational profiles, including the number, signature, and type, were not significantly different between the ASD patients and controls. Intriguingly, when considering genes with low-level brain somatic SNVs and ASD risk genes with damaging germline SNVs together, the merged set of genes carrying either somatic or germline SNVs in ASD patients was significantly involved in ASD-associated pathophysiology, including dendrite spine morphogenesis (p = 0.025), mental retardation (p = 0.012), and intrauterine growth retardation (p = 0.012). Additionally, the merged gene set showed ASD-associated spatiotemporal expression in the early and mid-fetal cortex, striatum, and thalamus (all p < 0.05). Patients with damaging mutations in the merged gene set had a greater ASD risk than did controls (odds ratio = 3.92, p = 0.025, 95% confidence interval = 1.12–14.79). The findings of this study suggest that brain somatic SNVs and germline SNVs may collectively contribute to ASD-associated pathophysiology.

<i>In Vitro</i> Bactericidal Effects of 625, 525, and 425 nm Wavelength (Red, Green, and Blue) Light-Emitting Diode Irradiation

Kim, SangWoo,Kim, JiSun,Lim, WonBong,Jeon, SangMi,Kim, OkSu,Koh, Jeong-Tae,Kim, Chang-Su,Choi, HongRan,Kim, OkJoon Mary Ann Liebert 2013 Photomedicine and laser surgery Vol.31 No.11

Brain somatic mutations in MTOR cause focal cortical dysplasia type II leading to intractable epilepsy

Lim, Jae Seok,Kim, Woo-il,Kang, Hoon-Chul,Kim, Se Hoon,Park, Ah Hyung,Park, Eun Kyung,Cho, Young-Wook,Kim, Sangwoo,Kim, Ho Min,Kim, Jeong A,Kim, Junho,Rhee, Hwanseok,Kang, Seok-Gu,Kim, Heung Dong,Kim, Nature Publishing Group 2015 Nature medicine Vol. No.

Focal cortical dysplasia type II (FCDII) is a sporadic developmental malformation of the cerebral cortex characterized by dysmorphic neurons, dyslamination and medically refractory epilepsy. It has been hypothesized that FCD is caused by somatic mutations in affected regions. Here, we used deep whole-exome sequencing (read depth, 412–668×) validated by site-specific amplicon sequencing (100–347,499×) in paired brain-blood DNA from four subjects with FCDII and uncovered a de novo brain somatic mutation, mechanistic target of rapamycin (MTOR) c.7280T>C (p.Leu2427Pro) in two subjects. Deep sequencing of the MTOR gene in an additional 73 subjects with FCDII using hybrid capture and PCR amplicon sequencing identified eight different somatic missense mutations found in multiple brain tissue samples of ten subjects. The identified mutations accounted for 15.6% of all subjects with FCDII studied (12 of 77). The identified mutations induced the hyperactivation of mTOR kinase. Focal cortical expression of mutant MTOR by in utero electroporation in mice was sufficient to disrupt neuronal migration and cause spontaneous seizures and cytomegalic neurons. Inhibition of mTOR with rapamycin suppressed cytomegalic neurons and epileptic seizures. This study provides, to our knowledge, the first evidence that brain somatic activating mutations in MTOR cause FCD and identifies mTOR as a treatment target for intractable epilepsy in FCD.

Effects of HSP27 downregulation on PDT resistance through PDT-induced autophagy in head and neck cancer cells

KIM, JISUN,LIM, HAESOON,KIM, SANGWOO,CHO, HYEJUNG,KIM, YONG,LI, XIAOJIE,CHOI, HONGRAN,KIM, OKJOON Spandidos Publications 2016 Oncology Reports Vol.35 No.4

<P>We previously reported that photodynamic therapy (PDT) induces cell death in head and neck cancer through both autophagy and apoptosis. Regulation of cell death by autophagy and apoptosis is important to enhance the effects of PDT. Autophagy maintains a balance between cell death and PDT resistance. Downregulation of heat shock protein 27 (HSP27) induces PDT resistance in head and neck cancer cells. Furthermore, HSP70 regulates apoptosis during oxidative stress. However, the role of HSPs in PDT-induced cell death through autophagy and apoptosis is unclear. Therefore, in the present study, we investigated the effects of HSP27 and HSP70 on PDT-induced cell death of oral cancer cells through autophagy and apoptosis. Cancer cells were treated with hematoporphyrin at varying doses, followed by irradiation at 635 nm with an energy density of 5 mW/cm(2). We determined the changes in HSP expression by determining the levels of PARP-1 and LC3II in PDT-resistant cells. Furthermore, we assessed cell death signaling after downregulating HSPs by transfecting specific siRNAs. We observed that PDT decreased HSP27 expression but increased HSP70 expression in the head and neck cancer cells. Treatment of cells with LC3II and PARP-1 inhibitors resulted in upregulation of HSP70 and HSP27 expression, respectively. Downregulation of HSP27 and HSP70 induced cell death and PDT resistance through autophagy and apoptosis. Moreover, downregulation of HSP27 in PDT-resistant cells resulted in enhanced survival. These results indicate that the regulation of HSP27 and HSP70 plays a principal role in increasing the effects of PDT by inducing autophagic and apoptotic cell death.</P>

기능성 위장장애 환자의 소화불량 제증상 치료에 있어서 콤비짐^(�)정의 임상효과

김동의,주재환,추상우,김형륵,조철균,김영진,김현종,김신곤 中央醫學社 1996 中央醫學 Vol.61 No.12

Functional dyspepsia has been considered, until recently, to be a nebulous syndrome, in part because of the lack of a structural explanation for the symptoms and because of the apparent heterogeneity of the patients labeled with this diagnosis. Although many definitions have been offered, there is now reasonable consensus that dyspepsia refers to persistent or recurrent pain or discomfort that is centered on the upper abdomen ; the discomfort may be characterized by postprandial fullness, early satiety, nausea or upper abdominal bloating. The diagnosis of dyspepsia must not be restricted to those with meal-related symptoms because there is no clinical condition, including chronic peptic ulceration, in which the symptoms are exclusively confined to the postprandial period. The majority of the patients with chronic or recurrent dyspepsia do not have a peptic ulcer or any other recognized structural or biochemical abnormality that definitely explains the symptoms ; these patients are classified as having functional dyspepsia. Ideally, therapy for functional dyspepsia should be targeted at correcting an individual's underlying pathophysiologic disturbances. However, the mechanisms that produce symptoms in patients with functional dyspepsia remain poorly understood. A polyvalent digestive product Combizym� has a powerful combination of enzymes with broad activity and broad pH spectrum. It acts from the stomach to the small intestine and has a complete digestive effect on protein, carbohyrate and fat. We treated Combizym� in patients with functional dyspepsia with open, noncomparative study. The results are as follows ; 1. The improvement of the symptoms were 96.4 % in nausea and vomiting, 92.6 % in bloating, other symptoms were also improved over 75 %. 2. There was only mild pruritus in a patient and others were well tolerated during the experiment. 3. Overall improvement rate was 86.7 % of 30 patients. In conclusion, Combizym� is a safe and effective digestive drug in patients with functional dyspepsia.

Synthesis, Characterization and Gas‑Sensing Properties of Pristine and SnS2 Functionalized TeO2 Nanowires

Sangwoo Kim,방재훈,최명식,Wansik Oum,Ali Mirzaei,Namgue Lee,Hyouk‑Chon Kwon,Dohyung Lee,Hyeongtag Jeon,Sang Sub Kim,Hyoun Woo Kim 대한금속·재료학회 2019 METALS AND MATERIALS International Vol.25 No.3

We report the gas-sensing properties of pristine and SnS2functionalized TeO2nanowires (NWs). TeO2NWs were synthesizedby a vapor–liquid–solid growth method, and SnS2functionalization was performed using an atomic layer depositiontechnique followed by thermal treatment. Structural and morphological analyses verified the formation of pristine and SnS2functionalized TeO2NWs with desired composition, phase, and morphology. Interestingly, sensing results showed that thepristine TeO2NW gas sensor had better sensing properties relative to the SnS2functionalized TeO2NW gas sensor. Anunderlying sensing mechanism is explained in detail, and reasons for the decrease of sensing performance with the SnS2functionalized TeO2NW sensor was attributed to the coverage of TeO2surface by the SnS2nanoparticles.

Nutrition and feed approach according to pig physiology

Sangwoo Park,Byeonghyeon Kim,Younghoon Kim,Sheena Kim,Kibeom Jang,Younghwa Kim,Juncheol Park,Minho Song,Sangnam Oh 충남대학교 농업과학연구소 2016 Korean Journal of Agricultural Science Vol.43 No.5

MIL 시뮬레이터를 이용한 6속 AT 기반 2축 병렬형 하이브리드 자동차의 과도상태 해석

김상우(Sangwoo Kim),황현수(Hyunsoo Hwang),김정민(Jeongmin Kim),홍정호(Jeongho Hong),김현수(Hyunsoo Kim) 한국자동차공학회 2009 한국자동차공학회 부문종합 학술대회 Vol.2009 No.4

Model in the loop(MIL) simulator is developed for a 6 speed AT based 2-shaft parallel hybrid electric vehicle(HEV) to investigate the transient characteristics such as mode change, tip-in and tip-out etc. First, powertrain model of the HEV is constructed using AMESim and control algorithm of the HCU is developed based on MATLAB Simulink. Using the AMESim simulator and MATLAB based HCU, MIL simulator is developed. It is found from the MIL simulation results that the transient characteristics such as driveshaft torque, engine and motor torque, clutch engagement state can be effectively evaluated.

Cloning metallothionein gene in Zacco platypus and its potential as an exposure biomarker against cadmium.

Lee, Sangwoo,Kim, Cheolmin,Kim, Jungkon,Kim, Woo-Keun,Shin, Hyun Suk,Lim, Eun-Suk,Lee, Jin Wuk,Kim, Sunmi,Kim, Ki-Tae,Lee, Sung-Kyu,Choi, Cheol Young,Choi, Kyungho D. Reidel Pub. Co ; Springer 2015 Environmental monitoring and assessment Vol.187 No.7

<P>Zacco platypus, pale chub, is an indigenous freshwater fish of East Asia including Korea and has many useful characteristics as indicator species for water pollution. While utility of Z. platypus as an experimental species has been recognized, genetic-level information is very limited and warrants extensive research. Metallothionein (MT) is widely used and well-known biomarker for heavy metal exposure in many experimental species. In the present study, we cloned MT in Z. platypus and evaluated its utility as a biomarker for metal exposure. For this purpose, we sequenced complete complementary DNA (cDNA) of MT in Z. platypus and carried out phylogenetic analysis with its sequences. The transcription-level responses of MT gene following the exposure to CdCl2 were also assessed to validate the utility of this gene as an exposure biomarker. Analysis of cDNA sequence of MT gene demonstrated high conformity with those of other fish. MT messenger RNA (mRNA) expression and enzymatic MT content significantly increased following CdCl2 exposure in a concentration-dependent manner. The level of CdCl2 that resulted in significant MT changes in Z. platypus was within the range that was reported from other fish. The MT gene of Z. platypus sequenced in the present study can be used as a useful biomarker for heavy metal exposure in the aquatic environment of Korea and other countries where this freshwater fish species represents the ecosystem.</P>

한국어판 지각된 강요(Perceived Coercion Questionnaire) 척도의 타당화 연구

김용석(Kim, Yongseok),이종호(Lee, Jongho),신수경(Shin, Sookyung),김용묵(Kim, Yongmug),송승연(Song, Seungyeon),이경진(Lee, Kyoungjin),김소연(Kim, Soyeon),김상우(Kim, Sangwoo) 한국정신건강사회복지학회 2018 정신보건과 사회사업 Vol.46 No.2

다수의 중독 클라이언트가 강요에 의해서 치료에 참여하기 때문에 강요의 역할을 이해하는 것이 중요하다. 그러나 지금까지 알코올사용장애 클라이언트가 경험했던 강요에 대해서 연구된 바는 없다. 강요에 대한 연구가 부족한 이유는 다양하겠지만, 강요를 측정할 수 있는 도구의 부재도 관련이 있을 것이다. 지각된 강요 척도(PCQ)는 치료 강요에 대한 중독 클라이언트의 주관적 지각을 측정할 뿐 아니라 다양한 강요의 출처를 측정해주는 유용한 도구이다. 본 연구는 중독분야에서 사용할 수 있는 지각된 강요 척도의 한국어판을 개발하여 관련 연구의 활성화에 기여하고자 하였다. 217명의 알코올사용장애 클라이언트를 대상으로 실시된 한국어판 지각된 강요 척도에 대한 평가결과는 매우 양호하였다. 확인적 요인분석에서 한국어판 지각된 강요 척도는 영어판 척도처럼 6개의 하위요인으로 구성된 것으로 나타났다. 한국어판 지각된 강요 척도의 내적 일관성 신뢰도는 다양한 방법으로 평가되었고 평가결과는 매우 양호하였다. 또한, 한국어판 지각된 강요 척도의 수렴타당도와 판별타당도 결과도 양호하였다. 이는 한국어판 지각된 강요 척도를 구성하는 6개 하위요인에 적재된 문항들은 동일한 요인을 측정하였고 각 요인이 서로 구별되는 개념을 측정하는 정도가 양호하다는 의미로 해석될 수 있다. 한국어판 지각된 강요 척도의 개발은 중독 클라이언트가 인지하는 강요를 측정 가능하게 하여 관련 연구의 활성화에 기여할 것으로 기대된다. Since many people with alcohol use disorder enter treatment by coercion, it is important to understand the role of coercion in treatment entry process. However, studies on coercion have been very scarce. The reason for the lack of research on coercion may be related to the absence of proper instruments measuring the construct. The Perceived Coercion Questionnaire is an instrument not only to measure individuals’ perception of coercion but also measuring various sources of coercion. The purpose of this study is to develop a Korean version of the Perceived Coercion Questionnaire (PCQ). A total of 217 people with alcohol use disorder participated in this study. The findings of this study were satisfactory. Confirmatory factor analysis confirmed that the Korean version of the PCQ, like its English version, is composed of 6 factors (self, family, legal, finance, health, work). The Korean version of the PCQ showed high internal consistency reliability and satisfactory construct validity. The development of the Korean version of the PCQ would contribute to conducting scientific studies on coercion.