25 research outputs found

    Role of S&T in Korea's economic development

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    노트 : The Annual 2001 Conference of the American Society for Public Administration at Rutgers University, New Jersey, USA. 행사명 : 파키스탄 경제개발전략과

    A Preterm Infant with Feeding Aspiration Diagnosed with BOR Syndrome, Confirmed Case by Whole-Genome Sequencing and Structural Variant Calling

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    Branchiootorenal (BOR) syndrome is a rare autosomal dominant inherited disease with a prevalence of approximately 1 in 40,000 newborns. This disease is characterized by hearing loss, preauricular pits, branchial fistulas or cysts, and renal dysplasia. We discovered a case of BOR syndrome in a premature 2-week-old female infant with a gestational age of 32 weeks and two days. She and her family had major symptoms and a family history of BOR. BOR syndrome was confirmed by whole-genome sequencing and structural variant calling, which revealed an EYA1 exon 5–6 deletion. The infant had recurrent sleep and feeding cyanosis with second branchial anomalies. Via videofluoroscopic swallowing study and a modified barium swallow test, penetration into the vocal cords was observed before and during swallowing when bottle feeding. This is the first report of a preterm infant early diagnosed with BOR syndrome in which deletion margin was accurately identified by whole-genome sequencing and structural variant calling in Republic of Korea

    Daily injection of melatonin inhibits insulin resistance induced by chronic mealtime shift

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    Shift work disorders have become an emerging concern worldwide. Shift disorders encompass a wide range of illnesses that have yet to be identified. The study focused on the relationship between shift work disorders and insulin resistance. Previously, it was reported that advancing the usual mealtime of mice triggered insulin resistance. Here, the hypothesis that chronic mealtime shifts induce oxidative damage leading to chronic diseases such as type 2 diabetes was tested. It was found that mealtime shift causes imbalances between anti-oxidative capacity and reactive oxygen species (ROS) levels, indicating increased oxidative damage during the light/rest phase. This study further demonstrated that daily supplementation of antioxidants at the appropriate time of day inhibited insulin resistance caused by chronic mealtime shifts, suggesting significant and chronic health implications for shift workers. In conclusion, it was confirmed that increased ROS levels caused by mealtime shift induce insulin resistance, which is inhibited by the antioxidant melatonin. © 2022 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.TRU

    Disrupted-in-schizophrenia 1 enhances the quality of circadian rhythm by stabilizing BMAL1

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    Disrupted-in-schizophrenia 1 (DISC1) is a scaffold protein that has been implicated in multiple mental disorders. DISC1 is known to regulate neuronal proliferation, signaling, and intracellular calcium homeostasis, as well as neurodevelopment. Although DISC1 was linked to sleep-associated behaviors, whether DISC1 functions in the circadian rhythm has not been determined yet. In this work, we revealed that Disc1 expression exhibits daily oscillating pattern and is regulated by binding of circadian locomotor output cycles kaput (CLOCK) and Brain and muscle Arnt-like protein-1 (BMAL1) heterodimer to E-box sequences in its promoter. Interestingly, Disc1 deficiency increases the ubiquitination of BMAL1 and de-stabilizes it, thereby reducing its protein levels. DISC1 inhibits the activity of GSK3 beta, which promotes BMAL1 ubiquitination, suggesting that DISC1 regulates BMAL1 stability by inhibiting its ubiquitination. Moreover, Disc1-deficient cells and mice show reduced expression of other circadian genes. Finally, Disc1-LI (Disc1 knockout) mice exhibit damped circadian physiology and behaviors. Collectively, these findings demonstrate that the oscillation of DISC1 expression is under the control of CLOCK and BMAL1, and that DISC1 contributes to the core circadian system by regulating BMAL1 stability.11Nsciescopu

    The representative protein expression profiles of the liver.

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    <p>Mouse liver tissues were harvested at the indicated circadian times and analyzed by western blotting. The circadian expression profiles of clock proteins in WT, <i>Bmal1</i><sup><i>+/GTΔC</i></sup>, <i>Bmal1</i><sup><i>GTΔC/GTΔC</i></sup>, <i>Bmal1</i><sup><i>+/—</i></sup>and <i>Bmal1</i><sup><i>-/-</i></sup> mice (n = 3).</p

    A Novel <i>Bmal1</i> Mutant Mouse Reveals Essential Roles of the C-Terminal Domain on Circadian Rhythms

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    <div><p>The mammalian circadian clock is an endogenous biological timer comprised of transcriptional/translational feedback loops of clock genes. <i>Bmal1</i> encodes an indispensable transcription factor for the generation of circadian rhythms. Here, we report a new circadian mutant mouse from gene-trapped embryonic stem cells harboring a C-terminus truncated <i>Bmal1</i> (<i>Bmal1</i><sup><i>GTΔC</i></sup>) allele. The homozygous mutant (<i>Bmal1</i><sup><i>GTΔC/GTΔC</i></sup>) mice immediately lost circadian behavioral rhythms under constant darkness. The heterozygous (<i>Bmal1</i><sup><i>+/GTΔC</i></sup>) mice displayed a gradual loss of rhythms, in contrast to <i>Bmal1</i><sup><i>+/-</i></sup> mice where rhythms were sustained. <i>Bmal1</i><sup><i>GTΔC/GTΔC</i></sup> mice also showed arrhythmic mRNA and protein expression in the SCN and liver. Lack of circadian reporter oscillation was also observed in cultured fibroblast cells, indicating that the arrhythmicity of <i>Bmal1</i><sup><i>GTΔC/GTΔC</i></sup> mice resulted from impaired molecular clock machinery. Expression of clock genes exhibited distinct responses to the mutant allele in <i>Bmal1</i><sup><i>+/GTΔC</i></sup> and <i>Bmal1</i><sup><i>GTΔC/GTΔC</i></sup> mice. Despite normal cellular localization and heterodimerization with CLOCK, overexpressed BMAL1<sup>GTΔC</sup> was unable to activate transcription of <i>Per1</i> promoter and BMAL1-dependent CLOCK degradation. These results indicate that the C-terminal region of <i>Bmal1</i> has pivotal roles in the regulation of circadian rhythms and the <i>Bmal1</i><sup><i>GTΔC</i></sup> mice constitute a novel model system to evaluate circadian functional mechanism of BMAL1.</p></div
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