• Biomolecules & Therapeutics
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• 제25권3호
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• pp.231-238
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• 2017

Myelin is a specialized structure of the nervous system that both enhances electrical conductance and insulates neurons from external risk factors. In the central nervous system, polarized oligodendrocytes form myelin by wrapping processes in a spiral pattern around neuronal axons through myelin-related gene regulation. Since these events occur at a distance from the cell body, post-transcriptional control of gene expression has strategic advantage to fine-tune the overall regulation of protein contents in situ. Therefore, many research interests have been focused to identify RNA binding proteins and their regulatory mechanism in myelinating compartments. Fragile X mental retardation protein (FMRP) is one such RNA binding protein, regulating its target expression by translational control. Although the majority of works on FMRP have been performed in neurons, it is also found in the developing or mature glial cells including oligodendrocytes, where its function is not well understood. Here, we will review evidences suggesting abnormal translational regulation of myelin proteins with accompanying white matter problem and neurological deficits in fragile X syndrome, which can have wider mechanistic and pathological implication in many other neurological and psychiatric disorders.

• 대한생식의학회:학술대회논문집
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• 대한불임학회 2003년도 제44차 춘계학술대회
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• pp.47-53
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• 2003

• Journal of the Korean Academy of Child and Adolescent Psychiatry
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• 제2권1호
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• pp.66-75
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• 1991

자폐장애의 유전적 요소를 조사하기 위하여 DSM-III-R의 진단기준으로 자폐장애에 부합한 38명의 아동에서 염색체 검사를 실시하였다. 본 연구의 대상은 남아 28명과 여아 10명이었으며, 평균 연령은 $108.8{\pm}28.5개월(70{\sim}156개월)$이었다. 염색체 핵형검사 결과 모든 대상 아동에서 46XX 혹은 46XY로서 염색체 수에는 이상이 없었다. Fragile X는 한 명에서도 발견되지 않았다. Fragile X 이외의 염색체 구조의 이상은 14명(36.8%)에서 발견되었으며, 그 양상은 breakage 11명, gap 2명, breakage와 gap이 공존하는 경우 1명이었다. Denver의 염색체 분류에 의한 이상 염색체 군은 A군 4명, C군 3명, 두 군 이상의 이상은 A군과 B군 동시에 발견된 경우가 1명, A군과 C군 동시 발견이 3명, A군과 E군 동시 발견이 1명, C군과 E군 동시 발견이 1명, A군 B군과 C군 동시 발견이 1명이었다. 염색체 구조에 이상이 있는 집단과 이상이 없는 집단을 DSM-III-R에 의한 자폐장애 증상 항목별로 비교하여 본 바, 모든 증상의 빈도는 양 집단간에 통계적으로 유의한 차이가 없었다.

• BMB Reports
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• 제39권6호
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• pp.766-773
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• 2006

Fragile-X-syndrome (FXS) is the most common type of inherited cognitive impairment. The underlying molecular alteration consists of a CGG-repeat amplification within the FMR-1 gene. The phenotype is only apparent once a threshold in the number of repeats has been exceeded (full mutation). The aim of this study was to characterize the FMR-1 CGG-repeat status in Argentine patients exhibiting mental retardation. A total of 330 blood samples from patients were analyzed by PCR and Southern blot analysis. Initially, DNA from 78 affected individuals were studied by PCR. Since this method is unable to detect high molecular weight alleles, however, we undertook a second approach using the Southern blotting technique to analyze the CGG repeat number and methylation status. Southern blot analysis showed an altered pattern in 14 out of 240 (6%) unrelated patients, with half of them presenting a mosaic pattern. Eight out of 17 families (47%) showed a (suggest deleting highlight). The characteristic FXS pattern was identified in 8/17 families (47%), and in 4 of these families 25% of the individuals presented with a mosaic model. The expansion from pre-mutation to full mutation was shown to occur both at the pre and post zygotic levels. The detection of FXS mutations has allowed us to offer more informed genetic counseling, prenatal diagnosis and reliable patient follow-up.

• Asian-Australasian Journal of Animal Sciences
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• 제21권8호
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• pp.1103-1108
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• 2008

An investigation to determine frequency and distribution of folate sensitive chromosomal fragile sites was carried out in a Pakistani breed of Lohi sheep to uncover fragile site phenomena. The means and standard errors of aberrant cell count (AC) and Number of aberrations (NoA) in Lohi sheep were $0.56{\pm}0.15$ and $0.59{\pm}0.16$ in the control cultures. FUdR treated cells showed significantly higher (p<0.001) AC and NoA means ($2.18{\pm}0.33$ and $2.65{\pm}0.50$). The sex comparison for the frequency of expression indicated that males had significantly higher number of aberrant cells and total number of aberrations in FUdR cultures than the female group in Lohi sheep. The comparison of control cultures was however, not significantly different between the two groups. The regression analysis of FUdR-induced chromosomal fragility data analysis of the fragility data predicted very low ${\beta}$ of 0.325 and 0.412 for AC and NoA respectively. Lohi chromosomes expressed lesions in only 7 and 24 bands in the control and FUdR cultures respectively. The total number of significantly fragile bands in the Lohi genome was only 4. The X-chromosome of the Lohi sheep was highly stable at $5{\mu}g/ml$ FUdR with no fragile sites. The sex comparison for the distribution of fragile sites across the Lohi genome did not reveal any noticeable differences.

• 대한예방의학회:학술대회논문집
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• 대한예방의학회 2001년도 춘계 심포지움 연제집
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• pp.78-78
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• 2001

• Food Science and Biotechnology
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• 제17권5호
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• pp.976-982
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• 2008

The 10 species of marine green algae was collected from Jejudo(Island) in Korea. Methanolic and aqueous extracts were prepared and screened for inhibition activities against tumor cell growth. Of the tested samples, the sea staghorn (Codium fragile) aqueous extract (CFAE) showed the highest activity on CT-26 cell growth. Therefore, CFAE was selected for further experiments and the possibility to induce apoptosis by the CFAE was investigated. Flow cytometric analysis revealed that it dose-dependently increased apoptotic cells with hypodiploid DNA contents in CT-26 cell line. These results indicated that CFAE can suppress the growth of CT-26 cells through apoptosis. The CFAE decreased the protein expression of anti-apoptotic Bcl-xL and led to the activation of caspase-3 and -7. A crude polysaccharide was separated from CFAE and it mainly constituted with 61.2% galactose and 30.5% arabinose as analyzed by high performance liquid chromatography (HPLC).

• 한국동물학회:학술대회논문집
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• 한국동물학회 1999년도 한국생물과학협회 학술발표대회
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• pp.253.2-253
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• 1999

No Abstract, See Full Text

• BMB Reports
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• 제52권5호
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• pp.304-311
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• 2019

The cytoplasmic FMR1-interacting protein family (CYFIP1 and CYFIP2) are evolutionarily conserved proteins originally identified as binding partners of the fragile X mental retardation protein (FMRP), a messenger RNA (mRNA)-binding protein whose loss causes the fragile X syndrome. Moreover, CYFIP is a key component of the heteropentameric WAVE regulatory complex (WRC), a critical regulator of neuronal actin dynamics. Therefore, CYFIP may play key roles in regulating both mRNA translation and actin polymerization, which are critically involved in proper neuronal development and function. Nevertheless, compared to CYFIP1, neuronal function and dysfunction of CYFIP2 remain largely unknown, possibly due to the relatively less well established association between CYFIP2 and brain disorders. Despite high amino acid sequence homology between CYFIP1 and CYFIP2, several in vitro and animal model studies have suggested that CYFIP2 has some unique neuronal functions distinct from those of CYFIP1. Furthermore, recent whole-exome sequencing studies identified de novo hot spot variants of CYFIP2 in patients with early infantile epileptic encephalopathy (EIEE), clearly implicating CYFIP2 dysfunction in neurological disorders. In this review, we highlight these recent investigations into the neuronal function and dysfunction of CYFIP2, and also discuss several key questions remaining about this intriguing neuronal protein.

• Molecules and Cells
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• 제43권10호
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• pp.870-879
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• 2020

Dendrites require precise and timely delivery of protein substrates to distal areas to ensure the correct morphology and function of neurons. Many of these protein substrates are supplied in the form of ribonucleoprotein (RNP) complex consisting of RNA-binding proteins (RBPs) and mRNAs, which are subsequently translated in distal dendritic areas. It remains elusive, however, whether key RBPs supply mRNA according to local demands individually or in a coordinated manner. In this study, we investigated how Drosophila sensory neurons respond to the dysregulation of a disease-associated RBP, Ataxin-2 (ATX2), which leads to dendritic defects. We found that ATX2 plays a crucial role in spacing dendritic branches for the optimal dendritic receptive fields in Drosophila class IV dendritic arborization (C4da) neurons, where both expression level and subcellular location of ATX2 contribute significantly to this effect. We showed that translational upregulation through the expression of eukaryotic translation initiation factor 4E (eIF4E) further enhanced the ATX2-induced dendritic phenotypes. Additionally, we found that the expression level of another disease-associated RBP, fragile X mental retardation protein (FMRP), decreased in both cell bodies and dendrites when neurons were faced with aberrant upregulation of ATX2. Finally, we revealed that the PAM2 motif of ATX2, which mediates its interaction with poly(A)-binding protein (PABP), is potentially necessary for the decrease of FMRP in certain neuronal stress conditions. Collectively, our data suggest that dysregulation of RBPs triggers a compensatory regulation of other functionally-overlapping RBPs to minimize RBP dysregulation-associated aberrations that hinder neuronal homeostasis in dendrites.