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        A Lignin Molecular Brace Controls Precision Processing of Cell Walls Critical for Surface Integrity in <i>Arabidopsis</i>

        Lee, Yuree,Yoon, Taek Han,Lee, Jiyoun,Jeon, So Yeon,Lee, Jae Ho,Lee, Mi Kyoung,Chen, Huize,Yun, Ju,Oh, Se Yun,Wen, Xiaohong,Cho, Hui Kyung,Mang, Hyunggon,Kwak, June M. Elsevier 2018 Cell Vol.173 No.6

        <P><B>Summary</B></P> <P>The cell wall, a defining feature of plants, provides a rigid structure critical for bonding cells together. To overcome this physical constraint, plants must process cell wall linkages during growth and development. However, little is known about the mechanism guiding cell-cell detachment and cell wall remodeling. Here, we identify two neighboring cell types in <I>Arabidopsis</I> that coordinate their activities to control cell wall processing, thereby ensuring precise abscission to discard organs. One cell type produces a honeycomb structure of lignin, which acts as a mechanical “brace” to localize cell wall breakdown and spatially limit abscising cells. The second cell type undergoes transdifferentiation into epidermal cells, forming protective cuticle, demonstrating <I>de novo</I> specification of epidermal cells, previously thought to be restricted to embryogenesis. Loss of the lignin brace leads to inadequate cuticle formation, resulting in surface barrier defects and susceptible to infection. Together, we show how plants precisely accomplish abscission.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Two neighboring cell types coordinate cellular activities for organ separation </LI> <LI> A honeycomb structure of lignin acts as a “molecular brace” </LI> <LI> The lignin brace spatially restricts cell wall breakdown </LI> <LI> Lignin deposition ensures surface integrity of transdifferentiated epidermal cells </LI> </UL> </P> <P><B>Graphical Abstract</B></P> <P>[DISPLAY OMISSION]</P>

      • Synthesis and biological evaluation of 3-(2-aminoethyl) uracil derivatives as gonadotropin-releasing hormone (GnRH) receptor antagonists

        Kim, Seon-Mi,Lee, Minhee,Lee, So Young,Lee, Soo-Min,Kim, Eun Jeong,Kim, Jae Sun,Ann, Jihyae,Lee, Jiyoun,Lee, Jeewoo Elsevier 2018 European journal of medicinal chemistry Vol.145 No.-

        <P><B>Abstract</B></P> <P>We investigated a series of uracil analogues by introducing various substituents on the phenyl ring of the <I>N</I>-3 aminoethyl side chain and evaluated their antagonistic activity against human gonadotropin-releasing hormone (GnRH) receptors. Analogues with substituents at the ortho or meta position demonstrated potent in vitro antagonistic activity. Specifically, the introduction of a 2-OMe group enhanced nuclear factor of activated T-cells (NFAT) inhibition up to 6-fold compared to the unsubstituted analogue. We identified compound <B>12c</B> as a highly potent GnRH antagonist with moderate CYP inhibition. Compound <B>12c</B> showed potent and prolonged LH suppression after a single dose was orally administered in castrated monkeys compared to a known antagonist, Elagolix. We believe that our SAR study offers useful insights to design GnRH antagonists as a potential treatment option for endometriosis.</P> <P><B>Highlights</B></P> <P> <UL> <LI> A series of 3-(2-aminoethyl) uracil analogues were synthesized as GnRH antagonists. </LI> <LI> Compound <B>12c</B> showed highly potent GnRH antagonism with moderate CYP inhibition. </LI> <LI> Compound <B>12c</B> exhibited potent and prolonged LH suppression in castrated monkeys. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

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        Discovery of an Orally Bioavailable Gonadotropin-Releasing Hormone Receptor Antagonist

        Kim, Seon-Mi,Lee, Minhee,Lee, So Young,Park, Euisun,Lee, Soo-Min,Kim, Eun Jeong,Han, Min Young,Yoo, Taekyung,Ann, Jihyae,Yoon, Suyoung,Lee, Jiyoun,Lee, Jeewoo American Chemical Society 2016 Journal of medicinal chemistry Vol.59 No.19

        <P>We developed a compound library for orally available gonadotropin-releasing hormone (GnRH) receptor antagonists that were based on a uracil scaffold. On the basis of in vitro activity and CYP inhibition profile, we selected 18a (SKI2496) for further in vivo studies. Compound 18a exhibited more selective antagonistic activity toward the human GnRH receptors over the GnRHRs in monkeys and rats, and this compound also showed inhibitory effects on GnRH-mediated signaling pathways. Pharmacokinetic and pharmacodynamic evaluations of 18a revealed improved bioavailability and superior gonadotropic suppression activity compared with Elagolix, the most clinically advanced compound. Considering that 18a exhibited highly potent and selective antagonistic activity toward the hGnRHRs along with favorable pharmacokinetic profiles, we believe that 18a may represent a promising candidate for an orally available hormonal therapy.</P>

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        Education as a Protective Factor Moderating the Effect of Depression on Memory Impairment in Elderly Women

        Jiyoun Lee,Heyeon Park,Jeanyung Chey 대한신경정신의학회 2018 PSYCHIATRY INVESTIGATION Vol.15 No.1

        ObjectiveaaThe cognitive reserve theory explicates individual differences observed in the clinical manifestation of dementia despite similar brain pathology. Education, a popular proxy of the cognitive reserve, has been shown to have protective effects delaying the onset of clinical symptoms including memory. This study was conducted to test whether education can moderate the negative effect of depressive mood on memory performance in elderly women residing in the community. Methodsaa29 elderly “unschooled” female (less than 6 years of formal education) and 49 “schooled” female (6 or more years) people were compared with regard to association between depressive mood and verbal memory functioning, which were measured by the Geriatric Depression Scale and the Elderly Verbal Learning Test, respectively. ResultsaaThe results showed that completing or receiving more than primary school education significantly reduced the negative association between depressive mood and memory performance. Participants who did not complete primary schooling showed a decline in memory test scores depending on the level of depressive mood; whereas participants who have completed or received more than primary education displayed relatively stable memory function despite varying level of depressive mood. ConclusionaaOur findings imply that education in early life may have protective effects against memory impairment related to elderly depression.

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        Systematic editing of synthetic RIG-I ligands to produce effective antiviral and anti-tumor RNA immunotherapies

        Lee, Janghyun,Park, Eun-Byeol,Min, Jiyoun,Sung, Si-Eun,Jang, Yejin,Shin, Jin Soo,Chun, Dongmin,Kim, Ki-Hun,Hwang, Jihyun,Lee, Mi-Kyung,Go, Yun Young,Kwon, Dohyeong,Kim, Meehyein,Kang, Suk-Jo,Choi, Byo Oxford University Press 2018 Nucleic acids research Vol.46 No.4

        <P><B>Abstract</B></P><P>Retinoic acid-inducible gene I (RIG-I) recognizes double-stranded viral RNAs (dsRNAs) containing two or three 5′ phosphates. A few reports of 5′-PPP-independent RIG-I agonists have emerged, but little is known about the molecular principles underlying their recognition. We recently found that the bent duplex RNA from the influenza A panhandle promoter activates RIG-I even in the absence of a 5′-triphosphate moiety. Here, we report that non-canonical synthetic RNA oligonucleotides containing G-U wobble base pairs that form a bent helix can exert RIG-I-mediated antiviral and anti-tumor effects in a sequence- and site-dependent manner. We present synthetic RNAs that have been systematically modified to enhance their efficacy and we outline the basic principles for engineering RIG-I agonists applicable to immunotherapy.</P>

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        Effect of side chain hydrophobicity and cationic charge on antimicrobial activity and cytotoxicity of helical peptoids

        Lee, Jiyoun,Kang, Dahyun,Choi, Jieun,Huang, Wei,Wadman, Mayken,Barron, Annelise E.,Seo, Jiwon Elsevier 2018 Bioorganic & medicinal chemistry letters Vol.28 No.2

        <P><B>Abstract</B></P> <P>Peptoids are peptidomimetic polymers that are resistant to proteolysis and less prone to immune responses; thus, they can provide a practical alternative to peptides. Among the various therapeutic applications that have been explored, cationic amphipathic peptoids have demonstrated broad-spectrum antibacterial activity, including activity towards drug-resistant bacterial strains. While their potency and activity spectrum can be manipulated by sequence variations, bacterial selectivity and systemic toxicity need to be improved for further clinical development. To this aim, we incorporated various hydrophobic or cationic residues to improve the selectivity of the previously developed antibacterial peptoid <B>1</B>. The analogs with hydrophobic residues demonstrated non-specific cytotoxicity, while those with an additional cationic residue showed improved selectivity and comparable antibacterial activity. Specifically, compared to <B>1</B>, peptoid <B>7</B> showed much lower hemolysis and cytotoxicity, while maintaining the antibacterial activity. Therefore, we believe that peptoid <B>7</B> has the potential to serve as a promising alternative to current antimicrobial therapies.</P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

      • KCI등재

        백신 접종의 혜택-위험 이해도 제고를 위한 통계정보 시각화 3종의 개발과 효과 검증

        이지연(Lee, Jiyoun),한영애(Hahn, Youngae) 인제대학교 디자인연구소 2021 Journal of Integrated Design Research (JIDR) Vol.20 No.4

        연구배경 코로나19 백신접종 개시 이후 질병관리청에서 게재해온 백신접종 후 이상반응 통계표는 (1)이상반응의 신고 비율(%)을 증상별 구분 없이 제시하고, (2)경증·중증·사망의 신고 건(count) 정보만 제시하며, (3)접종 후 이상반응이 없는 신고없음의 통계를 제시하지 않는다. 결과적으로 일부 뉴스 독자들이 현 통계표의 이상반응 신고 비율을 경증과 중증을 합산이 아니라 중증 비율로 오해하거나, 신고없음·경증·중증·사망의 비율을 실제보다 낮거나 높게 오인하면 향후 접종률의 저하 등 부정적인 결과로 이어질 수 있다. 연구방법 따라서 독자를 오도(誤導)하는 현 통계표의 문제점에 대응하여 개선된 통계표 3종(표, 막대_%, 막대_건)을 모바일 뉴스그래픽의 형식으로 제작하였다. 개선된 통계표는 (1)독자의 계산 착오를 방지하기 위해 접종 후 신고없음·경증·중증·사망의 건과 비율을 모두 계산하여 표로 제시하고, (2)여러 확률값을 직관적으로 비교할 수 있도록 막대그래프를 건과 비율 기준으로 시각화하여 병기하였다. 또 (3)중증·사망 통계는 0.05% 미만의 희박한 확률이지만 백신간 안전성 비교에 중요한 정보이므로 척도를 달리한 확대 그래프를 추가하여 강조하였다. (4 사망통계는 코로나19 확진 후 사망 비율보다 백신 접종 후 사망 비율이 낮음을 알리기 위해 두 비율값을 비교 제시하였다. 이후 20-30대 코로나 백신 미접종자를 대상으로 현 통계표와 개선된 통계표 3종의 커뮤니케이션 효과를 비교하는 온라인 설문조사를 실시하여 피험자 390명이 3개 그룹에 무작위로 할당되어 대조 조건(현 통계표)과 실험 조건 3종 중 1개를 순서대로 보고 응답하였다. 연구결과 백신접종의 혜택–위험 판단에 필요한 정보로 피험자들이 선택한 항목은 사망(%), 중증(%), 사망(건), 경증(%), 신고없음(%) 순으로 나타나 이상반응 비율 정보 제공의 필요성이 발견되었다. 또 실험 조건 3종은 이상반응 크기의 축어적(verbatim), 핵심적(gist) 지식의 전달에서 모두 대조 조건에 비해 높은 효과를 보였으나 실험 조건 3종간 유의한 차이는 없다. 학력 그룹 간 비교에서는 일부 대조 조건과 3개 실험 조건 모두에서 대재졸-고졸 그룹간 유의한 이해도의 차이가 발견되었다. 개선 통계표를 보고 접종후 신고없음의 비율이 높고 중증 비율이 낮으며 사망 비율은 코로나19 확진후 사망비율에 비해 낮음을 알게된 피험자들의 인지된 백신접종의 혜택-위험 크기는 전체적으로 혜택을 크게 인지하는 방향으로 변화하였다. 결론 현 통계표의 불충분한 정보와 부정 관점을 비율 정보 시각화 및 긍정-부정의 균형 잡힌 관점으로 교정한 개선 통계표(표, 막대_%, 막대_건)는 현 통계표 보다 (1)정확한 축어적 지식전달에 효과적이었으며, (2)그 중 막대_%, 막대_건 그래프는 핵심적 지식전달에 효과적이었고 (3)피험자의 인지된 혜택-위험 크기는 개선된 통계표를 본 뒤 혜택 방향으로 유의하게 향상되었다. 본 연구의 발견 사항은 단기적으로는 중증 이상 부작용의 확률을 과장되게 인식하여 백신접종을 꺼리는 집단의 인식을 교정하는 목적으로 활용될 수 있다. 보다 장기적으로는 향후 코로나19와 같은 모든 신종 감염병의 예방을 위한 백신 안전성의 대국민 커뮤니케이션이 필요한 경우 그 가이드라인 수립의 기초자료로 채택될 수 있다. Background In South Korea, the government-issued Adverse Reaction Statistics following COVID-19 Vaccination table, which has been cited in many news articles, is problematic in that (1) the adverse reaction rate(%) is calculated with all adverse reaction cases combined, (2) while the individual counts of mild, severe, and death cases are presented without rates, and (3) the counts and rate of asymptomatic cases are not reported at all. As a result, the table can cause news readers to misperceive the severe case rate higher while asymptomatic case rate lower than the real rates. Such a misunderstanding can lower the reader’s vaccination intention. Methods Three alternative statistics tables were developed to provide all counts and rates of asymptomatic, mild, severe, and death cases: one as a table and the other two designed with additional bar graph visualizations of the rate(%) and count. As the severe case and death rates are small probabilities less than 0.05%, magnified graphs were added for the reader’s between-vaccine safety comparison; the COVID-19 death rate was also added for accurate vaccination benefit-risk comparison. The communication effectiveness of alternative tables was tested in an online quantitative study with 390 participants who were randomly assigned to one of the three groups to read the current table and one of the alternative tables. Results Participants responded that the rates(%) of all asymptomatic, mild, severe, and death cases were important, in addition to the death counts, for accurate comparison of vaccination benefit-risk. All alternative tables were more effective in communicating verbatim and gist knowledge than the current table, so the participants’ comprehension scores were significantly improved. The score differences between the alternatives were not significant, but the differences between educational levels were significant. After reading the alternative tables, the participants’ perceived benefit was significantly increased. Conclusions The findings from this study-the effectiveness of investigating what information the readers need for vaccination benefit-risk comparison from a balanced perspective first and presenting the needed rates of asymptomatic, mild, severe, and death cases with visualizations-can be applied to improve the information quality of related news graphics, and more fundamentally, to the development of guidelines for public benefit-risk communication of health behavior including vaccination.

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