• Title/Summary/Keyword: Biology and Life Science

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Stomach clusterin as a gut-derived feeding regulator

  • Cherl NamKoong;Bohye Kim;Ji Hee Yu;Byung Soo Youn;Hanbin Kim;Evonne Kim;So Young Gil;Gil Myoung Kang;Chan Hee Lee;Young-Bum Kim;Kyeong-Han Park;Min-Seon Kim;Obin Kwon
    • BMB Reports
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    • v.57 no.3
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    • pp.149-154
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    • 2024
  • The stomach has emerged as a crucial endocrine organ in the regulation of feeding since the discovery of ghrelin. Gut-derived hormones, such as ghrelin and cholecystokinin, can act through the vagus nerve. We previously reported the satiety effect of hypothalamic clusterin, but the impact of peripheral clusterin remains unknown. In this study, we administered clusterin intraperitoneally to mice and observed its ability to suppress fasting-driven food intake. Interestingly, we found its synergism with cholecystokinin and antagonism with ghrelin. These effects were accompanied by increased c-fos immunoreactivity in nucleus tractus solitarius, area postrema, and hypothalamic paraventricular nucleus. Notably, truncal vagotomy abolished this response. The stomach expressed clusterin at high levels among the organs, and gastric clusterin was detected in specific enteroendocrine cells and the submucosal plexus. Gastric clusterin expression decreased after fasting but recovered after 2 hours of refeeding. Furthermore, we confirmed that stomachspecific overexpression of clusterin reduced food intake after overnight fasting. These results suggest that gastric clusterin may function as a gut-derived peptide involved in the regulation of feeding through the gut-brain axis.

miR-185 inhibits endoplasmic reticulum stress-induced apoptosis by targeting Na+/H+ exchanger-1 in the heart

  • Kim, Jin Ock;Kwon, Eun Jeong;Song, Dong Woo;Lee, Jong Sub;Kim, Do Han
    • BMB Reports
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    • v.49 no.4
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    • pp.208-213
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    • 2016
  • Prolonged ER stress (ERS) can be associated with the induction of apoptotic cell death in various heart diseases. In this study, we searched for microRNAs affecting ERS in the heart using in silico and in vitro methods. We found that miR-185 directly targets the 3′-untranslated region of Na+/H+ exchanger-1 (NHE-1), a protein involved in ERS. Cardiomyocyte ERS-triggered apoptosis induced by 100 ng/ml tunicamycin (TM) or 1 μM thapsigargin (TG), ERS inducers, was significantly reduced by miR-185 overexpression. Protein expression of pro-apoptotic markers such as CCAAT/enhancer-binding protein homologous protein (CHOP) and cleaved-caspase-3 was also markedly reduced by miR-185 in a dose-dependent manner. Cariporide (20 μM), a pharmacological inhibitor of NHE-1, also attenuated ERS-induced apoptosis in cardiomyocytes and CHOP protein expression, suggesting that NHE-1 plays an important role in ERS-associated apoptosis in cardiomyocytes. Collectively, the present results demonstrate that miR-185 is involved in cardio-protection against ERS-mediated apoptotic cell death.

Isolation and Identification of Entomopathogenic Fungus from the Pine Wilt Disease Vector, Monochamus alternatus Hope(Coleoptera: Cerambycidae) in Korea

  • Shin, Tae-Young;Choi, Jae-Bang;Bae, Sung-Min;Cha, Ye-Rim;Oh, Jeong-Mi;Koo, Hyun-Na;Woo, Soo-Dong
    • International Journal of Industrial Entomology and Biomaterials
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    • v.18 no.2
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    • pp.125-129
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    • 2009
  • Entomopathogenic fungi were isolated directly from a cadaver of adult Monochamus alternatus supporting fungal sporulation, using a semi-selective medium and then screened several fungal colonies. The pathogenicity of each fungus was tested using oak longicorn beetle, Moechotypa diphysis, as substitutive insect. As the result, only one of them showed high pathogenicity against M. diphysis, with up to 100% mortality within 21 days of inoculation. Selected fungus was named as MaW1 and identified by Beauveria bassiana using microscopic examination and DNA analysis. Pathogenicity was also evaluated to M. alternatus.

Structural insights showing how arginine is able to be glycosylated by pathogenic effector proteins

  • Park, Jun Bae;Yoo, Youngki;Cho, Hyun-Soo
    • BMB Reports
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    • v.51 no.12
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    • pp.609-610
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    • 2018
  • Glycosylation is one form of protein modification and plays a key role in protein stability, function, signaling regulation and even cancer. NleB and SseK are bacterial effector proteins and possess glycosyltransferase activity, even though they have different substrate preferences. NleB/SseKs transfer the GlcNAc sugar to an arginine residue of host proteins, leading to reduced $NF-{\kappa}B-dependent$ responses. By combining X-ray crystallography, NMR, molecular dynamics, enzyme kinetic assays and in vivo experiments, we demonstrated that a conserved HEN (His-Glu-Asn) motif in the active site plays a key role in enzyme catalysis and virulence. The lid-domain regulates the opening and closing of the active site and the HLH domain determines the substrate specificity. Our findings provide evidence for the enzymatic mechanism by which arginine can be glycosylated by SseK/NleB enzymes.

Synthesis of Substituted Imidazolidin-2-ones as Aminoacyl-tRNA Synthase Inhibitors

  • Eum, Hee-Sung;Lee, Yu-No;Kim, Song-Mi;Baek, A-Young;Son, Min-Ky;Lee, Keun-Woo;Ko, Seung-Whan;Kim, Sung-Hoon;Yun, Sae-Young;Lee, Won-Koo;Ha, Hyun-Joon
    • Bulletin of the Korean Chemical Society
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    • v.31 no.3
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    • pp.611-614
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    • 2010
  • Substituted imidazolidin-2-ones deduced as potential inhibitors of IleRS by docking simulations were synthesized from an aziridine-2-carboxaldehyde. Reductive amination of an aziridine-2-carboxaldehyde with dipeptides for the substituents at N1 and followed by aziridine-ring expansion with triphosgene afforded 4-chloromethylimidazolidin-2-ones whose chloride were further manipulated towards phenylurea, pyrimidin-2-yl-urea or benzenesulfonamide at C4.

Molecular Characterization of Small Heat Shock Protein(hsp20.8A) from the Silkworm, Bombyx mori

  • Hwang, Jae-Sam;Go, Hyun-Jeong;Goo, Tae-Won;Seong, Su-Il;Yun, Eun-Young;Ahn, Mi-Young;Kim, Seong-Ryul;Park, Kwan-Ho;Kim, Ik-Soo;Jeon, Jae-Pil;Kang, Seok-Woo
    • International Journal of Industrial Entomology and Biomaterials
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    • v.15 no.1
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    • pp.75-78
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    • 2007
  • To define the molecular mechanism of initiation and termination of diapause during the embryogenesis of silkworm, Bombyx mori, mRNA transcripts from diapausing eggs and diapause activated eggs were compared with differential expression using cDNA array. Among those clones, mRNA transcript from hsp20.8A, which was expressed at a high level in diapausing eggs that had been incubated at $25^{\circ}C$ for 30 days after oviposition, whereas, in the eggs exposed to $15^{\circ}C$ for 30 days, $5^{\circ}C$ for 60 days, the expression of mRNA decreased. On the other hand, the expression of mRNA during embryogenesis observed abundantly at 4 to 6 days after heat-HCl treatment and later at 9 to 10 days after just before hatching. This result was suggested for us that hsp20.8A was expressed in response to embryogenesis as well as physical stress.

The Role of Hippo Pathway in Cancer Stem Cell Biology

  • Park, Jae Hyung;Shin, Ji Eun;Park, Hyun Woo
    • Molecules and Cells
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    • v.41 no.2
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    • pp.83-92
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    • 2018
  • The biological significance and deregulation of the Hippo pathway during organ growth and tumorigenesis have received a surge of interest in the past decade. The Hippo pathway core kinases, MST1/2 and LATS1/2, are tumor suppressors that inhibit the oncogenic nuclear function of YAP/TAZ and TEAD. In addition to earlier studies that highlight the role of Hippo pathway in organ size control, cell proliferation, and tumor development, recent evidence demonstrates its critical role in cancer stem cell biology, including EMT, drug resistance, and self-renewal. Here we provide a brief overview of the regulatory mechanisms of the Hippo pathway, its role in cancer stem cell biology, and promising therapeutic interventions.

Molecular Characterization and Morphology of Two Endophytic Peyronellaea Species from Pinus koraiensis in Korea

  • Deng, Jian Xin;Paul, Narayan Chandra;Li, Mei Jia;Seo, Eun-Young;Sung, Gi-Ho;Yu, Seung-Hun
    • Mycobiology
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    • v.39 no.4
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    • pp.266-271
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    • 2011
  • Species of Phoma and its allies were isolated during a survey on the diversity of endophytic fungi associated with pine trees in Korea. Based on the phylogenetic analyses of internal transcribed spacer and ${\beta}$-tubulin gene sequences, two Phoma-like species from the needles of Pinus koraiensis were identified as Peyronellaea calorpreferens and P. glomerata. They were also morphologically identified based on the previous descriptions. Here, we report P. calorpreferens and P. glomerata being present in Korea as endophytic fungi in Pinus koraiensis.

CRISPR base editor-based targeted random mutagenesis (BE-TRM) toolbox for directed evolution

  • Rahul Mahadev Shelake;Dibyajyoti Pramanik;Jae-Yean Kim
    • BMB Reports
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    • v.57 no.1
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    • pp.30-39
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    • 2024
  • Directed evolution (DE) of desired locus by targeted random mutagenesis (TRM) tools is a powerful approach for generating genetic variations with novel or improved functions, particularly in complex genomes. TRM-based DE involves developing a mutant library of targeted DNA sequences and screening the variants for the desired properties. However, DE methods have for a long time been confined to bacteria and yeasts. Lately, CRISPR/Cas and DNA deaminase-based tools that circumvent enduring barriers such as longer life cycle, small library sizes, and low mutation rates have been developed to facilitate DE in native genetic environments of multicellular organisms. Notably, deaminase-based base editing-TRM (BE-TRM) tools have greatly expanded the scope and efficiency of DE schemes by enabling base substitutions and randomization of targeted DNA sequences. BE-TRM tools provide a robust platform for the continuous molecular evolution of desired proteins, metabolic pathway engineering, creation of a mutant library of desired locus to evolve novel functions, and other applications, such as predicting mutants conferring antibiotic resistance. This review provides timely updates on the recent advances in BE-TRM tools for DE, their applications in biology, and future directions for further improvements.