http://chineseinput.net/에서 pinyin(병음)방식으로 중국어를 변환할 수 있습니다.
변환된 중국어를 복사하여 사용하시면 됩니다.
Generation of Dyrk1a knockout rat by using CRISPR-Cas9 system
Kyungrim Yi,Yonghun Sung,Dongkyu Kim,Hee-Kyung Kim,Tae-Jun Kwon,Dongseon Kim,Chang-Hoon Shin,Hee-Young Yang 한국실험동물학회 2021 한국실험동물학회 학술발표대회 논문집 Vol.2021 No.7
Backgrounds Dyrk1a (the dual specificity tyrosine phosphorylation-regulated kinase 1A) is an enzyme that in humans is encoded by the DYRK1A gene. Dyrk1a is a member of the DYRK family which plays key roles in the control of cell proliferation and differentiation. Dyrk1a is known for their importance in body growth and brain physiology. Previous studies have shown that homozygotes knockout mice are embryonic lethal, though haploinsufficiency of Dyrk1a leads to developmental delay and decreased brain size in mice. To investigate the effect of the knockdown of Dyrk1a in rats is identical which observed in mice, we generated genetically engineered rat model of haploinsufficiency of DYRK1A gene. Methods To figure out the roles of DYRK1A gene, we induced Dyrk1a knockdown rats by deleting 11 nucleotides in exon 7 using CRISPR/Cas9 system. We selected a target showed higher efficiency in their activity for generating Dyrk1a haploinsufficiency rats. Oocytes were collected from hyper-ovulated female SD rats, and genetically modified by micro-injection of purified RNA and CRISPR/Cas9 protein. Results We performed embryo transfer to surrogate female rats 5 times and got 6 to 14 pups per one recipient rat. Dyrk1a haploinsufficiency rats showed smaller body size and decreased brain size compared to wild-type rats. The protein level of sirtuin1(SirT1) phosphorylated by Dyrk1a also decreased in the brain of knockdown rats. Seeing that the protein level of signal transducer and activator of transcription3(STAT3) was also decreased, it suggests that SirT1 and STAT3 activities in brain are down-regulated in Dyrk1a haploinsufficiency rats. Conclusion The results obtained in this study indicate that Dyrk1a haploinsufficiency rats showed comparable phenotype with mice. The exact molecular and cellular mechanisms that are targeted by the inhibition of Dyrk1a are still to be discovered. Rats are more preferred to study in brain diseases, we propose this model can be a powerful tool in brain research such as Autism and Alzheimer’s.
Prevalence of insomnia and its relationship to menopausal status in middle-aged Korean women
SHIN, CHOL,LEE, SANGYEOL,LEE, TAEWOOK,SHIN, KYUNGRIM,YI, HYERYEON,KIMM, KUCHAN,CHO, NAMHAN Blackwell Science Pty 2005 Psychiatry and clinical neurosciences Vol.59 No.4
<P>Abstract </P><P>Although the prevalence of insomnia and the association of insomnia with menopause have been well reported, not much work has been conducted in population-based research on insomnia and menopause in Korea. The purpose of the present report was to determine overall and different prevalence of insomnia by menopausal status, and the relationship between insomnia and menopause in a population-based sample of middle-aged Korean women. A total of 96.1% of 2497 randomly selected middle-aged Korean women participated. Insomnia was defined as occurring three times a week or more in the previous month. Subjects were categorized into three groups: premenopaues, perimenopause, and postmenopause. The overall prevalence of insomnia in middle-aged Korean women was 14.3%. The most common symptom of insomnia was difficulty maintaining sleep (9.7%), followed by difficulty initiating sleep (7.9%), and early morning awakening (7.5%). Multiple logistic regression analysis revealed that menopause was independently associated with insomnia after adjusting for confounding factors such as age, income, and depression. Perimenopause was significantly associated with a dramatic increase in the risk of insomnia, but there was no significant association for postmenopause. The major finding is that insomnia is significantly associated with the menopausal transition. The prevalence of insomnia increases significantly by the transition from premenopause to perimenopause, but not to postmenopause. A further prospective study is needed to investigate the influence of menopause on insomnia.</P>
KIM, JINYOUNG,CHOI, CHANGHO,SHIN, KYUNGRIM,YI, HYERYEON,PARK, MINGYU,CHO, NAMHAN,KIMM, KUCHAN,SHIN, CHOL Blackwell Science Pty 2005 Psychiatry and clinical neurosciences Vol.59 No.3
<P>Abstract </P><P>The present study was purposed to identify the prevalence of restless legs syndrome (RLS) and its associated factors in the Korean adult population. Among a total of 9939 participants derived from the Korean Health and Genome Study, 12.1% of subjects (men, 8.5%; women, 15.4%) suffered from RLS. Factors independently related with RLS were older age and frequent fatigue in both men and women.</P>
Ha, Shinwon,Jeong, Seol-Hwa,Yi, Kyungrim,Chung, Kyung Min,Hong, Caroline Jeeyeon,Kim, Seong Who,Kim, Eun-Kyoung,Yu, Seong-Woon American Society for Biochemistry and Molecular Bi 2017 The Journal of biological chemistry Vol.292 No.33
<P>In the adult brain, programmed death of neural stem cells is considered to be critical for tissue homeostasis and cognitive function and is dysregulated in neurodegeneration. Previously, we have reported that adult rat hippocampal neural (HCN) stem cells undergo autophagic cell death (ACD) following insulin withdrawal. Because the apoptotic capability of the HCN cells was intact, our findings suggested activation of unique molecular mechanisms linking insulin withdrawal to ACD rather than apoptosis. Here, we report that phosphorylation of autophagy-associated protein p62 by AMP-activated protein kinase (AMPK) drives ACD and mitophagy in HCN cells. Pharmacological inhibition of AMPK or genetic ablation of the AMPK alpha 2 subunit by clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 genome editing suppressed ACD, whereas AMPK activation promoted ACD in insulin-deprived HCN cells. We found that following insulin withdrawal AMPK phosphorylated p62 at a novel site, Ser-293/Ser-294 (in rat and human p62, respectively). Phosphorylated p62 translocated to mitochondria and induced mitophagy and ACD. Interestingly, p62 phosphorylation at Ser-293 was not required for staurosporine-induced apoptosis in HCN cells. To the best of our knowledge, this is the first report on the direct phosphorylation of p62 by AMPK. Our data suggest that AMPK-mediated p62 phosphorylation is an ACD-specific signaling event and provide novel mechanistic insight into the molecular mechanisms in ACD.</P>