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GIT1 is associated with ADHD in humans and ADHD-like behaviors in mice
Won, Hyejung,Mah, Won,Kim, Eunjin,Kim, Jae-Won,Hahm, Eun-Kyoung,Kim, Myoung-Hwan,Cho, Sukhee,Kim, Jeongjin,Jang, Hyeran,Cho, Soo-Churl,Kim, Boong-Nyun,Shin, Min-Sup,Seo, Jinsoo,Jeong, Jaeseung,Choi, S Nature Publishing Group, a division of Macmillan P 2011 Nature medicine Vol.17 No.5
Attention deficit hyperactivity disorder (ADHD) is a psychiatric disorder that affects ??% of school-aged children; however, the mechanisms underlying ADHD remain largely unclear. Here we report a previously unidentified association between G protein??coupled receptor kinase??interacting protein-1 (GIT1) and ADHD in humans. An intronic single-nucleotide polymorphism in GIT1, the minor allele of which causes reduced GIT1 expression, shows a strong association with ADHD susceptibility in humans. Git1-deficient mice show ADHD-like phenotypes, with traits including hyperactivity, enhanced electroencephalogram theta rhythms and impaired learning and memory. Hyperactivity in Git1<SUP>??/??</SUP> mice is reversed by amphetamine and methylphenidate, psychostimulants commonly used to treat ADHD. In addition, amphetamine normalizes enhanced theta rhythms and impaired memory. GIT1 deficiency in mice leads to decreases in ras-related C3 botulinum toxin substrate-1 (RAC1) signaling and inhibitory presynaptic input; furthermore, it shifts the neuronal excitation-inhibition balance in postsynaptic neurons toward excitation. Our study identifies a previously unknown involvement of GIT1 in human ADHD and shows that GIT1 deficiency in mice causes psychostimulant-responsive ADHD-like phenotypes.
Autism spectrum disorder causes, mechanisms, and treatments: focus on neuronal synapses
Won, Hyejung,Mah, Won,Kim, Eunjoon Frontiers Media S.A. 2013 Frontiers in molecular neuroscience Vol.6 No.-
<P>Autism spectrum disorder (ASD) is a group of developmental disabilities characterized by impairments in social interaction and communication and restricted and repetitive interests/behaviors. Advances in human genomics have identified a large number of genetic variations associated with ASD. These associations are being rapidly verified by a growing number of studies using a variety of approaches, including mouse genetics. These studies have also identified key mechanisms underlying the pathogenesis of ASD, many of which involve synaptic dysfunctions, and have investigated novel, mechanism-based therapeutic strategies. This review will try to integrate these three key aspects of ASD research: human genetics, animal models, and potential treatments. Continued efforts in this direction should ultimately reveal core mechanisms that account for a larger fraction of ASD cases and identify neural mechanisms associated with specific ASD symptoms, providing important clues to efficient ASD treatment.</P>
Selected SALM (synaptic adhesion-like molecule) family proteins regulate synapse formation.
Mah, Won,Ko, Jaewon,Nam, Jungyong,Han, Kihoon,Chung, Woo Suk,Kim, Eunjoon The Society 2010 The Journal of neuroscience Vol.30 No.16
<P>Synaptic cell adhesion molecules regulate various steps of synapse formation. Despite the great diversity of neuronal synapses, relatively few adhesion molecules with synaptogenic activity have been identified. Synaptic adhesion-like molecules (SALMs) are members of a family of cell adhesion molecules known to regulate neurite outgrowth and synapse maturation; however, the role of SALMs in synapse formation remains unknown. We found that expression of the SALM family proteins SALM3 and SALM5 in nonneural and neural cells induces both excitatory and inhibitory presynaptic differentiation in contacting axons. SALM3 and SALM5 proteins are enriched in synaptic fractions, and form strong (SALM3) or weak (SALM5) complexes with postsynaptic density-95 (PSD-95), an abundant postsynaptic scaffolding protein at excitatory synapses. Aggregation of SALM3, but not SALM5, on dendritic surfaces induces clustering of PSD-95. Knockdown of SALM5 reduces the number and function of excitatory and inhibitory synapses. These results suggest that selected SALM family proteins regulate synapse formation, and that SALM3 and SALM5 may promote synapse formation through distinct mechanisms.</P>
Autistic-like social behaviour in Shank2-mutant mice improved by restoring NMDA receptor function
Won, Hyejung,Lee, Hye-Ryeon,Gee, Heon Yung,Mah, Won,Kim, Jae-Ick,Lee, Jiseok,Ha, Seungmin,Chung, Changuk,Jung, Eun Suk,Cho, Yi Sul,Park, Sae-Geun,Lee, Jung-Soo,Lee, Kyungmin,Kim, Daesoo,Bae, Yong Chul Nature Publishing Group, a division of Macmillan P 2012 Nature Vol.486 No.7402
Autism spectrum disorder (ASD) is a group of conditions characterized by impaired social interaction and communication, and restricted and repetitive behaviours. ASD is a highly heritable disorder involving various genetic determinants. Shank2 (also known as ProSAP1) is a multi-domain scaffolding protein and signalling adaptor enriched at excitatory neuronal synapses, and mutations in the human SHANK2 gene have recently been associated with ASD and intellectual disablility. Although ASD-associated genes are being increasingly identified and studied using various approaches, including mouse genetics, further efforts are required to delineate important causal mechanisms with the potential for therapeutic application. Here we show that Shank2-mutant (Shank2<SUP>??/??</SUP>) mice carrying a mutation identical to the ASD-associated microdeletion in the human SHANK2 gene exhibit ASD-like behaviours including reduced social interaction, reduced social communication by ultrasonic vocalizations, and repetitive jumping. These mice show a marked decrease in NMDA (N-methyl-d-aspartate) glutamate receptor (NMDAR) function. Direct stimulation of NMDARs with d-cycloserine, a partial agonist of NMDARs, normalizes NMDAR function and improves social interaction in Shank2<SUP>??/??</SUP> mice. Furthermore, treatment of Shank2<SUP>??/??</SUP> mice with a positive allosteric modulator of metabotropic glutamate receptor 5 (mGluR5), which enhances NMDAR function via mGluR5 activation, also normalizes NMDAR function and markedly enhances social interaction. These results suggest that reduced NMDAR function may contribute to the development of ASD-like phenotypes in Shank2<SUP>??/??</SUP> mice, and mGluR modulation of NMDARs offers a potential strategy to treat ASD.
안경사 국가시험 문항개발 기준 ( 2000 년판 ) 작성 연구 ( 2 )
이원진(Won Jin Lee),원찬희(Chan Hee Won),마기중(Ki Choong Mah),강성수(Sung Soo Kang),육도진(Do Jin Ruck),박혜정(Hae Jong Park) 한국안광학회 2001 한국안광학회지 Vol.6 No.1
In this study, the results were that the duty of optician was analysed with DACUM(Developing A Curriculum Method). Task/Skill Matrix was formed and selected the elements above 2.15 points with the job description. The job specification made out the job description and the preference survey for the optician with the job model. These elements made a draft of drawing up standard of the Optician National Licensing Examination by Job Analysis.
설문조사에서 불성실 응답의 원인과 조사설계 단계에서의 예방
박원우(Won-Woo Park),이유우(Yoowoo Lee),마성혁(Sunghyuck Mah),김자영(Jayoung Kim),배수현(Suhyun Bae),지선영(Seonyoung Ji) 한국경영학회 2021 經營學硏究 Vol.50 No.5
This study investigates the level of Korean researchers awareness of careless responding (CR) in surveys, the causes of CR, as well as the potential remedies available with regards to survey design. We first reviewed 827 survey studies published in seven major journals in the field of business administration and analyzed the level of recognition of Korean researchers regarding CR. We also investigated the causes of CR through a literature review that particularly focused on the motives and burdens of respondents. We then conducted in-depth interviews with academic and practical experts to investigate the perceptions and practices regarding CR. Finally, based on the literature review and the in-depth interviews, we drew up measures to prevent CR. We suggest that there need to be academic standards that prompt researchers to report specific CR prevention or detection methods used for their research in a more detailed manner. This study, as a cornerstone, contributes to further discussions and the development of preventive measures of CR in the Korean scholarly community, particularly in the field of business administration.
이원진,원찬희,마기중,성덕용,강성수,육도진,박혜정 한국보건의료인국가시험원 2004 보건의료교육평가 Vol.1 No.1
This study shows the optician' s job analysis, some questionaire and their analysis. Job description drafed, the standard of questionaire was fixed. Job description is establised on the results of the job analysis by DACUM( Developing A Curriculum Method). The job description formed above 2.15 referred to the results of survey of the importance and perfomance frequency of the job. These elements made a draft of drawing up standard of the Optician National Licensing Examination by Job Analysis.
박원우(Won-woo Park),마성혁(Sung Hyuck Mah),배수현(Su hyun Bae),지선영(Seon Young Ji),이유우(Yoo Woo Lee),김자영(Ja Young Kim) 한국경영학회 2020 經營學硏究 Vol.49 No.2
This study investigates the phenomenon of ‘careless responding’ that prevails in surveys. Specifically, we focus on methods of detection and the effects of screening careless responding. First, this study discusses the diverse definitions and types of careless responding. Methods of detection are introduced in the following triangular categorization: direct, unobtrusive, and statistical. The theoretical review portion provides a comparative summary of detection methods and their advantages and disadvantages to help future researchers apply a suitable one to their own study designs. Furthermore, this study conducts an empirical study to identify the impact of screening careless responding on statistical results, analyzing survey data from 3,030 employees working in a major conglomerate in Korea. The major findings are as follows: (1) According to the applied method, the target and the proportion of screened responses varied, ranging from 0.5% to 14% at maximum. Only a small proportion was detected coincidentally by two or more methods. (2) The screening of careless responding only had a slight impact on statistical figures of factor analysis, correlations, and regression. Such less than moderate impacts were in line with earlier findings and less threatening to the validation of research models. (3) Lastly, we demonstrated a multi-hurdling method that adopted two methods sequentially. To conclude, the study discusses possible applications of detection methods and avenues for future research.