45 research outputs found

    Inah Park, Organ

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    Choral Improvisation sur le Victimae Paschali Laudes / Charles Tournemire; Partita Ach, was soll ich Sünder machen BWV 770 / Johann Sebastian Bach; Sonate Der 94. Psalm / Julius Reuk

    Inah Park, Organ

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    Concerto in D minor, BWV 596 / Johann Sebastian Bach; From Trios, Op. 47 / Max Reger; Passacaglia et thema fugatum, BWV 582 / Johann Sebastian Bach; Fantasie über den Choral “Ein feste Burg ist unser Gott” / Max Rege

    Inah Park, Organ

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    Präludium und Fuge a-Moll, BWV 543 / Johann Sebastian Bach; Fantasie No.3 Es-Dur / Johann Gottfried Müthel; Schmücke dich, o liebe Seele, BWV 654 / J.S. Bach; Jesus Christus, unser Heiland, BWV 688 / J.S. Bach; Von Gott will ich nicht lassen, BWV 658 / J.S. Bach; Fantasie und Fuge c-Moll, Wq. 119, No. 7 / Carl Philipp Emanuel Bach; Toccata E-Dur, BWV 566 (C Major Version) / J.S. Bac

    Gut Microbial Metabolites Induce Changes in Circadian Oscillation of Clock Gene Expression in the Mouse Embryonic Fibroblasts

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    Circadian rhythm is an endogenous oscillation of about 24-h period in many physiological processes and behaviors. This daily oscillation is maintained by the molecular clock machinery with transcriptional-translational feedback loops mediated by clock genes including Period2 (Per2) and Bmal1. Recently, it was revealed that gut microbiome exerts a significant impact on the circadian physiology and behavior of its host; however, the mechanism through which it regulates the molecular clock has remained elusive. 3-(4-hydroxyphenyl)propionic acid (4-OH-PPA) and 3-phenylpropionic acid (PPA) are major metabolites exclusively produced by Clostridium sporogenes and may function as unique chemical messengers communicating with its host. In the present study, we examined if two C. sporogenes-derived metabolites can modulate the oscillation of mammalian molecular clock. Interestingly, 4-OH-PPA and PPA increased the amplitude of both PER2 and Bmal1 oscillation in a dosedependent manner following their administration immediately after the nadir or the peak of their rhythm. The phase of PER2 oscillation responded differently depending on the mode of administration of the metabolites. In addition, using an organotypic slice culture ex vivo, treatment with 4-OH-PPA increased the amplitude and lengthened the period of PER2 oscillation in the suprachiasmatic nucleus and other tissues. In summary, two C. sporogenes-derived metabolites are involved in the regulation of circadian oscillation of Per2 and Bmal1 clock genes in the host's peripheral and central clock machineries.1

    Multiplexed CRISPR-Cas9 system in a single adeno-associated virus to simultaneously knock out redundant clock genes

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    The mammalian molecular clock is based on a transcription-translation feedback loop (TTFL) comprising the Period1, 2 (Per1, 2), Cryptochrome1, 2 (Cry1, 2), and Brain and Muscle ARNT-Like 1 (Bmal1) genes. The robustness of the TTFL is attributed to genetic redundancy among some essential clock genes, deterring genetic studies on molecular clocks using genome editing targeting single genes. To manipulate multiple clock genes in a streamlined and efficient manner, we developed a CRISPR-Cas9-based single adeno-associated viral (AAV) system targeting the circadian clock (CSAC) for essential clock genes including Pers, Crys, or Bmal1. First, we tested several single guide RNAs (sgRNAs) targeting individual clock genes in silico and validated their efficiency in Neuro2a cells. To target multiple genes, multiplex sgRNA plasmids were constructed using Golden Gate assembly and packaged into AAVs. CSAC efficiency was evident through protein downregulation in vitro and ablated molecular oscillation ex vivo. We also measured the efficiency of CSAC in vivo by assessing circadian rhythms after injecting CSAC into the suprachiasmatic nuclei of Cas9-expressing knock-in mice. Circadian locomotor activity and body temperature rhythms were severely disrupted in these mice, indicating that our CSAC is a simple yet powerful tool for investigating the molecular clock in vivo. © 2021, The Author(s).1

    Projection of Cancer Incidence and Mortality From 2020 to 2035 in the Korean Population Aged 20 Years and Older

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    Objectives: This study aimed to identify the current patterns of cancer incidence and estimate the projected cancer incidence and mortality between 2020 and 2035 in Korea. Methods: Data on cancer incidence cases were extracted from the Korean Statistical Information Service from 2000 to 2017, and data on cancer-related deaths were extracted from the National Cancer Center from 2000 to 2018. Cancer cases and deaths were classified according to the International Classification of Diseases, 10th edition. For the current patterns of cancer incidence, age-standardized incidence rates (ASIRs) and age-standardized mortality rates were investigated using the 2000 mid-year estimated population aged over 20 years and older. A joinpoint regression model was used to determine the 2020 to 2035 trends in cancer. Results: Overall, cancer cases were predicted to increase from 265 299 in 2020 to 474 085 in 2035 (growth rate: 1.8%). The greatest increase in the ASIR was projected for prostate cancer among male (7.84 vs. 189.53 per 100 000 people) and breast cancer among female (34.17 vs. 238.45 per 100 000 people) from 2000 to 2035. Overall cancer deaths were projected to increase from 81 717 in 2020 to 95 845 in 2035 (average annual growth rate: 1.2%). Although most cancer mortality rates were projected to decrease, those of breast, pancreatic, and ovarian cancer among female were projected to increase until 2035. Conclusions: These up-to-date projections of cancer incidence and mortality in the Korean population may be a significant resource for implementing cancer-related regulations or developing cancer treatments

    Current Situation and Issue of Industrial Accident Compensation Insurance

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    Industrial Accident Compensation Insurance (IACI) has a history of about 50 yr, and is the oldest social insurance system in Korea. After more than 20 times of revision improvements in benefits, its contents and claim systems have been upgraded. It became the protector of injured workers and their families, and at the same time became the system which could cope with both financial burden of employers and their responsibilities. However, there are some issues to be reformed to upgrade the IACI: 1) the problems in the approval system of occupational diseases, 2) quality improvement of workers' compensation medical care, 3) vocational rehabilitation and return to work, 4) workers' compensation premiums and out-of-pocket money of injured workers, 5) issues in application of IACI. Growth of IACI cannot be achieved by an effort of an individual. Efforts by workers, owners, and government, in addition to physicians and welfare professionals toward the same goal are required for the next level improvement of IACI

    DNMT (DNA methyltransferase) inhibitors radiosensitize human cancer cells by suppressing DNA repair activity

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    <p>Abstract</p> <p>Background</p> <p>Histone modifications and DNA methylation are two major factors in epigenetic phenomenon. Unlike the histone deacetylase inhibitors, which are known to exert radiosensitizing effects, there have only been a few studies thus far concerning the role of DNA methyltransferase (DNMT) inhibitors as radiosensitizers. The principal objective of this study was to evaluate the effects of DNMT inhibitors on the radiosensitivity of human cancer cell lines, and to elucidate the mechanisms relevant to that process.</p> <p>Methods</p> <p>A549 (lung cancer) and U373MG (glioblastoma) cells were exposed to radiation with or without six DNMT inhibitors (5-azacytidine, 5-aza-2'-deoxycytidine, zebularine, hydralazine, epigallocatechin gallate, and psammaplin A) for 18 hours prior to radiation, after which cell survival was evaluated via clonogenic assays. Cell cycle and apoptosis were analyzed via flow cytometry. Expressions of DNMT1, 3A/3B, and cleaved caspase-3 were detected via Western blotting. Expression of γH2AX, a marker of radiation-induced DNA double-strand break, was examined by immunocytochemistry.</p> <p>Results</p> <p>Pretreatment with psammaplin A, 5-aza-2'-deoxycytidine, and zebularine radiosensitized both A549 and U373MG cells. Pretreatment with psammaplin A increased the sub-G1 fraction of A549 cells, as compared to cells exposed to radiation alone. Prolongation of γH2AX expression was observed in the cells treated with DNMT inhibitors prior to radiation as compared with those treated by radiation alone.</p> <p>Conclusions</p> <p>Psammaplin A, 5-aza-2'-deoxycytidine, and zebularine induce radiosensitivity in both A549 and U373MG cell lines, and suggest that this effect might be associated with the inhibition of DNA repair.</p

    miRNA 에 의한 생체시계 유전자 Per2 조절

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    Circadian clock controls an organism&rsquo;s biological rhythm and regulates physiological conditions in response to external time cues. Most of living organisms have their own time-keeping mechanism that is maintained by transcriptional-translational autoregulatory feedback loops involving several clock genes such as Periods, Cryptochromes, Clock and Bmal1. Recent discoveries have found the relevance between changes in circadian oscillation and post-transcriptional modification by microRNAs (miRNAs). However, the specific mechanisms of miRNAs on circadian oscillation still remain unclear. This study demonstrated the regulatory effects of miR-24-3p and miR-25-3p on Period2 (Per2) expression by direct interaction with 3&rsquo; untranslated region (UTR) of Per2 using luciferase reporter assay. Furthermore, real-time bioluminescence analyses demonstrated that PER2 oscillation patterns were sensitive to intracellular concentration of miR-24-3p or miR-25-3p. Elevation of either miR-24-3p or miR-25p-3p resulted phase advancing and dampening, while down regulation of miR-24-3p and miR-25-3p caused phase delay and increase in relative amplitude of PER2 oscillation. In summary, miR-24-3p and miR-25-3p are involved in fine-tuning of circadian rhythmicity through regulating PER2 oscillation in conjunction with other post-translational modulators. ⓒ 2017 DGIST1. Introduction 7-- 2. Materials and Methods 11-- 3. Results 14-- 3.1 Functional Validation of Candidate microRNAs Targeting 3&rsquo;UTR of mouse Period2 mRNA 14-- 3.2 Overexpression of miR-24-3p or miR-25-3p Downregulates PER2 Expression in Real-time Bioluminescence Analysis 15-- 3.3 Inhibition of Endogenous miR-24-3p or miR-25-3p Upregulates PER2 Expression in Real-time Bioluminescence Analysis 16-- 3.4 3&rsquo; Untranslated Region of Per2 mRNA is Essential for miR-24-3p and miR-25-3p for Modulating Circadian Oscillation 16-- 4. Discussion 38-- 5. References 42생체시계는 24 시간의 주기성을 가지며 외부 환경에 대한 정보에 민감하게 반응하여 생체 주기를 조절하며 생물의 항상성 조절에 중요한 역할을 한다. 생체리듬은 자가 전사-번역을 조절하는 기작으로 구성되어 있으며 여러 종류의 생체시계 유전자가 관여한다. 지난 수 십년 간의 생체리듬 연구에 따르면 생체시계 관련 유전자의 자가 되먹임 조절 고리에 의하여 한 개체가 24 시간의 생체 내 일주기성을 지니게 된다는 결과가 밝혀졌다. 더욱 흥미로운 것은 miRNA 역시 특정 mRNA 의 전사 후 조절을 통하여 생체리듬의 세밀한 조절 역할을 수행한다는 것이다. 본 연구에서는 실시간 인광 분석 장비와 Per2::Luc Knock-in 배아섬유아세포를 응용하여 miRNA 가 PER2::LUC 단백질의 일주기 발현 양상에 어떠한 영향을 미치는가에 대한 실험을 수행하였다. In silico 데이터 분석을 통하여miR-24-3p와 miR-25-3p를 선별하였고 이 miRNA들이 Per2 mRNA 의 3&rsquo;-비번역 부위에 작용하는지 여부를 확인하기 위하여 유전자 조작을 가한 리포터 벡터를 사용하여 miRNA-mRNA 의 상호작용 확인하였다. 따라서 본 연구를 통하여 miR-24-3p 와 miR-25-3p 가 Per2 mRNA 의 3&rsquo;-비번역부위에 작용하여 Per2 유전자의 발현이 조절됨을 밝혔다. ⓒ 2017 DGISTMasterdCollectio
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