• 제목/요약/키워드: translational research

검색결과 530건 처리시간 0.026초

Ataxin-2 Dysregulation Triggers a Compensatory Fragile X Mental Retardation Protein Decrease in Drosophila C4da Neurons

  • Cha, In Jun;Lee, Davin;Park, Sung Soon;Chung, Chang Geon;Kim, Seung Yeon;Jo, Min Gu;Kim, Seung Yeol;Lee, Byung-Hoon;Lee, Young-Sam;Lee, Sung Bae
    • 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.

Lipid emulsion inhibits vasodilation induced by a toxic dose of bupivacaine by suppressing bupivacaine-induced PKC and CPI-17 dephosphorylation but has no effect on vasodilation induced by a toxic dose of mepivacaine

  • Cho, Hyunhoo;Ok, Seong Ho;Kwon, Seong Chun;Lee, Soo Hee;Baik, Jiseok;Kang, Sebin;Oh, Jiah;Sohn, Ju-Tae
    • The Korean Journal of Pain
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    • 제29권4호
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    • pp.229-238
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    • 2016
  • Background: The goal of this in vitro study was to investigate the effect of lipid emulsion on vasodilation caused by toxic doses of bupivacaine and mepivacaine during contraction induced by a protein kinase C (PKC) activator, phorbol 12,13-dibutyrate (PDBu), in an isolated endothelium-denuded rat aorta. Methods: The effects of lipid emulsion on the dose-response curves induced by bupivacaine or mepivacaine in an isolated aorta precontracted with PDBu were assessed. In addition, the effects of bupivacaine on the increased intracellular calcium concentration ($[Ca^{2+}]_i$) and contraction induced by PDBu were investigated using fura-2 loaded aortic strips. Further, the effects of bupivacaine, the PKC inhibitor GF109203X and lipid emulsion, alone or in combination, on PDBu-induced PKC and phosphorylation-dependent inhibitory protein of myosin phosphatase (CPI-17) phosphorylation in rat aortic vascular smooth muscle cells (VSMCs) was examined by western blotting. Results: Lipid emulsion attenuated the vasodilation induced by bupivacaine, whereas it had no effect on that induced by mepivacaine. Lipid emulsion had no effect on PDBu-induced contraction. The magnitude of bupivacaine-induced vasodilation was higher than that of the bupivacaine-induced decrease in $[Ca^{2+}]_i$. PDBu promoted PKC and CPI-17 phosphorylation in aortic VSMCs. Bupivacaine and GF109203X attenuated PDBu-induced PKC and CPI-17 phosphorylation, whereas lipid emulsion attenuated bupivacaine-mediated inhibition of PDBu-induced PKC and CPI-17 phosphorylation. Conclusions: These results suggest that lipid emulsion attenuates the vasodilation induced by a toxic dose of bupivacaine via inhibition of bupivacaine-induced PKC and CPI-17 dephosphorylation. This lipid emulsion-mediated inhibition of vasodilation may be partly associated with the lipid solubility of local anesthetics.

치과용 CAD/CAM 밀링기에 대한 치과의료종사자들의 선호도 조사 (Survey study on the Preference of Dental Medical Personnel for Dental CAD/CAM Milling Machines)

  • 송은성;김봉주;임영준;이준재
    • 대한치과보철학회지
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    • 제56권3호
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    • pp.188-198
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    • 2018
  • 목적: 최근 디지털 기술의 발달과 더불어 치과영역에서도 다양한 보철물 제작을 위해 Computer aided design/computer aided manufacture (CAD/CAM) 시스템의 사용이 확대되고 있다. CAD/CAM 시스템은 전통적인 방식의 보철물 제작의 단점을 극복하여, 치과의사와 치기공사가 보철물을 제작할 때, 환자에게 한 두 번의 병원 방문으로도 정확하고 정밀도 높은 보철물의 제공이 가능하게 할 수 있다. 본 논문은 현재 국내의 CAD/CAM 시스템 현황 및 인식을 파악함으로써 새로 장비를 도입할 때 고려해야 할 항목에 대한 조언을 제공하고자 한다. 대상 및 방법: 본 설문 조사는 서울대학교 치과 병원을 포함한 전국 298 명의 치과의사, 치과위생사 및 치과기공사를 대상으로 2016년 11월부터 12월까지 2 개월간 우편을 통해 실시하였다. 결과: 치과용 CAD/CAM 밀링기 구매 시 가장 고려하는 요인은 밀링기의 성능(64.43%)이었으며 용도는 치과보철물 제작과 임플란트용 맞춤형 지대주 제작이 49.33%로 가장 높았다. 또한, 응답자의 약 60% 이상이 CAD/CAM 밀링기가 만족할 만한 성능으로 개선된다면 새로운 장비의 구매에 대해 긍정적인 답변을 보였다. 결론: 설문조사 분석결과, 성능이 개선된 CAD/CAM 밀링기 디지털화 및 4차 산업혁명을 대비하는 치과산업에서 중요한 역할을 할 것으로 여겨진다.

수치해석을 활용한 마찰교반용접 공정의 온도 특성 분석 연구 (Study on Temperature Characteristics of Friction Stir Welding Process by Numerical Analysis)

  • 김무선
    • 한국산학기술학회논문지
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    • 제20권12호
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    • pp.513-518
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    • 2019
  • 마찰교반용접(Friction Stir Welding) 기술은 금속 소재를 대상으로 하는 용접기술 중의 하나로 용접대상이 되는 소재와 고속으로 회전하는 용접툴 사이의 마찰로 인한 열을 활용하여 소재의 융점 이하 온도에서 접합하는 기술이다. 이번 연구에서는 마찰교반용접을 진행할 때, 용접 대상물의 내부 온도 변화를 분석하기 위한 방법으로 수치해석기법을 사용하였다. 용접소재로는 마그네슘 합금인 AZ31을 고려하였으며, 용접현상을 멜팅풀(melting-pool)이 생성되는 유동특성으로 간주하고 유동해석을 수행하기 위해 유동특성 수치해석 툴인 FLUENT를 이용하였다. 용접과정의 유동해석을 진행하기 위해 용접소재는 고점도 뉴턴 유체로 가정하였고, 용접툴과 용접대상 소재의 경계면은 마찰 및 미끄러짐이 동시에 발생하는 조건으로 경계조건을 선정하였다. 그리고 용접툴의 회전속도 및 용접속도를 변수로 하여 다양한 해석을 진행하였다. 해석 결과로부터 용접툴의 회전속도가 높을수록, 용접속도가 느릴수록 소재 내 최고온도가 증가함을 확인할 수 있었으며, 그 중 용접툴의 회전속도 차이가 온도 변화에 더 큰 영향을 보임을 확인하였다.

히스톤 3 아세틸화(H3Ac)를 통한 De-Etiolated 1 (DET1)의 애기장대 생체시계 조절 (Regulation of Arabidopsis Circadian Clock by De-Etiolated 1 (DET1) Possibly via Histone 3 Acetylation (H3Ac))

  • 송해룡
    • 생명과학회지
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    • 제22권8호
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    • pp.999-1008
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    • 2012
  • 자기 현가적(self-sustaining) 조절 장치인 생체시계는 24시간 주기의 생체리듬을 조절하며 또한 생물체로 하여금 매일 변화하는 자연환경의 외부 신호를 인지할 수 있도록 해준다. 생체시계 유전자의 발현 조절은 전사/해독의 역환류 기작을 통해 이루어진다. 애기장대 LATE ELONGATED HYPOCOTYL (LHY)와 CIRCADIAN CLOCK-ASSOCIATED 1 (CCA1)는 아침에 최고조로 발현되며 해독된 LHY and CCA1는 저녁에 최고로 발현되는 TIMING OF CAB EXPRESSION1 (TOC1)의 발현을 억제한다. TOC1단백질은 LHY와 CCA1 발현을 촉진시킴으로써 생체시계의 핵심 진자(oscillator)를 형성한다. 동물에서 생체시계의 주요 전사 인자인CLOCK은 아세틸화효소 활성 기능을 가지며, 이는 생체시계의 기능 유지에 아세틸화의 중요함을 의미한다. 하지만 애기장대 생체시계에 아세틸화를 담당하는 인자에 대한 정보는 현재 보고된 바가 없다. 본 연구에서 DET1 (De-Etiolated1)는 암조건하에서 애기장대 생체시계 관련 핵심인자 중 하나인 LHY발현을 억제하는데 필요하며 이의 억제는 H3Ac 조절을 통해 이루어짐을 증명하였다. 하지만 LHY 아세틸화를 담당하는 효소의 발굴 및 이들 효소와 DET1과의 연결을 찾는 문제는 여전히 미재로 남아있다.

Effects of three-dimensionally printed polycaprolactone/β-tricalcium phosphate scaffold on osteogenic differentiation of adipose tissue- and bone marrow-derived stem cells

  • Park, Hannara;Kim, Jin Soo;Oh, Eun Jung;Kim, Tae Jung;Kim, Hyun Mi;Shim, Jin Hyung;Yoon, Won Soo;Huh, Jung Bo;Moon, Sung Hwan;Kang, Seong Soo;Chung, Ho Yun
    • 대한두개안면성형외과학회지
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    • 제19권3호
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    • pp.181-189
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    • 2018
  • Background: Autogenous bone grafts have several limitations including donor-site problems and insufficient bone volume. To address these limitations, research on bone regeneration is being conducted actively. In this study, we investigate the effects of a three-dimensionally (3D) printed polycaprolactone (PCL)/tricalcium phosphate (TCP) scaffold on the osteogenic differentiation potential of adipose tissue-derived stem cells (ADSCs) and bone marrow-derived stem cells (BMSCs). Methods: We investigated the extent of osteogenic differentiation on the first and tenth day and fourth week after cell culture. Cytotoxicity of the 3D printed $PCL/{\beta}-TCP$ scaffold was evaluated by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay, prior to osteogenic differentiation analysis. ADSCs and BMSCs were divided into three groups: C, only cultured cells; M, cells cultured in the 3D printed $PCL/{\beta}-TCP$ scaffold; D, cells cultured in the 3D printed $PCL/{\beta}-TCP$ scaffold with a bone differentiation medium. Alkaline phosphatase (ALP) activity assay, von Kossa staining, reverse transcription-polymerase chain reaction (RT-PCR), and Western blotting were performed for comparative analysis. Results: ALP assay and von Kossa staining revealed that group M had higher levels of osteogenic differentiation compared to group C. RT-PCR showed that gene expression was higher in group M than in group C, indicating that, compared to group C, osteogenic differentiation was more extensive in group M. Expression levels of proteins involved in ossification were higher in group M, as per the Western blotting results. Conclusion: Osteogenic differentiation was increased in mesenchymal stromal cells (MSCs) cultured in the 3D printed PCL/TCP scaffold compared to the control group. Osteogenic differentiation activity of MSCs cultured in the 3D printed PCL/TCP scaffold was lower than that of cells cultured on the scaffold in bone differentiation medium. Collectively, these results indicate that the 3D printed PCL/TCP scaffold promoted osteogenic differentiation of MSCs and may be widely used for bone tissue engineering.

Stage specific transcriptome analysis of liver tissue from a crossbred Korean Native Pig (KNP × Yorkshire)

  • Kumar, Himansu;Srikanth, Krishnamoorthy;Park, Woncheol;Lee, Kyung-Tai;Choi, Bong-Hwan;Kim, Jun-Mo;Lim, Dajeong;Park, Jong-Eun
    • Journal of Biomedical and Translational Research
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    • 제19권4호
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    • pp.116-124
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    • 2018
  • Korean Native Pig (KNP) has a uniform black coat color, excellent meat quality, white colored fat, solid fat structure and good marbling. However, its growth performance is low, while the western origin Yorkshire pig has high growth performance. To take advantage of the unique performance of the two pig breeds, we raised crossbreeds (KNP ${\times}$ Yorkshire to make use of the heterotic effect. We then analyzed the liver transcriptome as it plays an important role in fat metabolism. We sampled at two stages: 10 weeks and at 26 weeks. The stages were chosen to correspond to the change in feeding system. A total of 16 pigs (8 from each stage) were sampled and RNA sequencing was performed. The reads were mapped to the reference genome and differential expression analysis was performed with edgeR package. A total of 324 genes were found to be significantly differentially expressed (${\left|log2FC\right|}$ > 1 & q < 0.01), out of which 180 genes were up-regulated and 144 genes were down-regulated. Principal Component Analysis (PCA) showed that the samples clustered according to stages. Functional annotation of significant DEGs (differentially expressed genes) showed that GO terms such as DNA replication, cell division, protein phosphorylation, regulation of signal transduction by p53 class mediator, ribosome, focal adhesion, DNA helicase activity, protein kinase activity etc. were enriched. KEGG pathway analysis showed that the DEGs functioned in cell cycle, Ras signaling pathway, p53 signaling pathway, MAPK signaling pathway etc. Twenty-nine transcripts were also part of the DEGs, these were predominantly Cys2His2-like fold group (C2H2) family of zinc fingers. A protein-protein interaction (PPI) network analysis showed that there were three highly interconnected clusters, suggesting an enrichment of genes with similar biological function. This study presents the first report of liver tissue specific gene regulation in a cross-bred Korean pig.

필발(Piper longum Linn.)로부터 전립선암 세포사멸물질 pipernonaline의 분리 및 동정 (Purification and Identification of Apoptosis Modulator Pipernonaline from Piper longum Linn. against Prostate Cancer Cells)

  • 김광연;김윤진;이완;유선녕;조효진;이선이;이한승;손재학;오현철;안순철
    • 생명과학회지
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    • 제19권5호
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    • pp.671-675
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    • 2009
  • Prostate cancer has been a critical health problem due to an increase of prostate cancer-related deaths worldwide. Also, a frequent treatment option for prostate cancer is androgen ablation, but this treatment has a limited scope, especially for hormone-refractory cancer. There is an urgent need for the identification of alternative therapeutic strategies for prostate cancer. Previously, over one hundred species of dried-plant methanol extracts were tested for inhibitory effects on proliferation. One of them, Piper longum Linn. was selected based on its potent anti-proliferation effect. The dried root of P. longum Linn. was extracted with 100% methanol for 2-3 days and its extract was fractionated using chloroform. The chloroform layer was then subjected to column chromatography on silica gel, reverse phase-18 (RP-18) and Sephadex LH-20, in turn. Finally, the pure compound was obtained and identified as pipernonaline by NMR spectroscopic and physico-chemical analysis. In this study, anti-proliferation and cell cycle arrest effects of pipernonaline on human prostate cancer PC-3 cells were investigated using the MTT and PI staining, respectively. Our findings suggest that pipernonaline represents a dose-dependent growth inhibition pattern on PC-3 cells and, moreover, its growth inhibition is associated with sub-G1 and G0/G1 cell cycle accumulation in PC-3 cells. Also, these results provide an anticancer candidate for human prostate cancer.

Molecular Characterization of Ischemia-Responsive Protein 94 (irp94) Response to Unfolded Protein Responses in the Neuron

  • ;;;;권오유
    • 대한의생명과학회지
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    • 제12권2호
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    • pp.81-89
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    • 2006
  • The ischemia-responsive 94 gene (irp94) encoding a 94 kDa endoplasmic reticulum resident protein was investigated its molecular properties associated with unfoled protein responses. First, the expression of irp94 mRNA was tested after the reperfusion of the transient forebrain ischemia induction at the central nervous system in three Mongolian gerbils. Second, irp94 expression in PC12 cells, which are derived from transplantable rat pheochromocytoma cultured in the DMEM media, was tested at transcriptional and translational levels. The half life of irp94 mRNA was also determined In PC12 cells. Last, the changes of irp94 mRNA expression were investigated by the addition of various ER stress inducible chemicals (A23187, BFA, tunicamycin, DTT and $H_2O_2$) and proteasome inhibitors, and heat shock. High level expression of irp94 mRNA was detected after 3 hours reperfusion in the both sites of the cerebral cortex and hippocampus of the gerbil brain. The main regulation of irp94 mRNA expression in PC 12 cells was determined at the transcriptional level. The half life of irp94 mRNA in PC12 cells was approximately 5 hours after the initial translation. The remarkable expression of irp94 mRNA was detected by the treatment of tunicamycin, which blocks glycosylation of newly synthesized polypeptides, and $H_2O_2$, which induces apoptosis. When PC12 cells were treated with the cytosol proteasome inhibitors such as ALLN (N-acetyl-leucyl-norleucinal) and MG 132 (methylguanidine), irp94 mRNA expression was increased. These results indicate that expression of irp94 was induced by ER stress including oxidation condition and glycosylation blocking in proteins. Expression of irp94 was increased when the cells were chased after heat shock, suggesting that irp94 may be involved in recovery rather than protection against ER stresses. In addition, irp94 expression was remarkably increased when cytosol proteasomes were inhibited by ALLN and MG 132, suggesting that irp94 plays an important role for maintaining the ERAD (endoplasmic reticulum associated degradation) function.

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Spoilage Lactic Acid Bacteria in the Brewing Industry

  • Xu, Zhenbo;Luo, Yuting;Mao, Yuzhu;Peng, Ruixin;Chen, Jinxuan;Soteyome, Thanapop;Bai, Caiying;Chen, Ling;Liang, Yi;Su, Jianyu;Wang, Kan;Liu, Junyan;Kjellerup, Birthe V.
    • Journal of Microbiology and Biotechnology
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    • 제30권7호
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    • pp.955-961
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    • 2020
  • Lactic acid bacteria (LAB) have caused many microbiological incidents in the brewing industry, resulting in severe economic loss. Meanwhile, traditional culturing method for detecting LAB are time-consuming for brewers. The present review introduces LAB as spoilage microbes in daily life, with focus on LAB in the brewing industry, targeting at the spoilage mechanism of LAB in brewing industry including the special metabolisms, the exist of the viable but nonculturable (VBNC) state and the hop resistance. At the same time, this review compares the traditional and novel rapid detection methods for these microorganisms which may provide innovative control and detection strategies for preventing alcoholic beverage spoilage, such as improvement of microbiological quality control using advanced culture media or different isothermal amplification methods.