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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>
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>
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>
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>
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>
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.
창의성의 확산과 수렴적 사고를 중심으로 한 프로토타이핑의 활용도 고찰
이지연 ( Lee Jiyoun ),나건 ( Nah Ken ) 한국디자인혁신협회 2016 산업디자인학연구 Vol.10 No.3
This study looked into developing a methodology for the manifestation of creativity as a solution to changes in design concepts and the role of designers from environmental, especially technological change. This study understood prototype as practical implementation of ideas for creativity and their simulation and looked into the feasibility of various types of prototyping in the design process. In light of dividing creativity into divergent and convergent thinking, appropriate types of prototyping for each step of the design process was analyzed through literature review. Additionally, the study looked into the similarities and differences of various definitions of creativity and prototyping, and provides a case study of products created through prototyping that accord with both divergent thinking for various ideas and convergent thinking for a single answer. In order to increase the credibility of argument, 4 case studies were cited from successful design for corporations. Divergent thinking is utilized easily, quickly and repetitively in low-fidelity prototyping in order to help idea generation in the first half of the design process, and convergent thinking was found to be optimal in the second half when function and form are developed and certified based on user experience. Through this, the study reached a conclusion that repetition and appropriate disposition of divergent and convergent thinking of creativity during a design process help idea proliferation and the most optimal result through viewing of the resulting product and its closet model. For future studies, the paper expects the development of an evaluation and inspection system that's most appropriate for prototyping in order to maximize its effectiveness.
제품 디자인 프로세스에서 입체가 아이디에이션(ideation)에 미치는 영향 ; 디자인 고등학교 학생들을 중심으로
이지연 ( Lee Jiyoun ),나건 ( Nah Ken ) 한국디자인혁신협회 2017 산업디자인학연구 Vol.11 No.1
21C calls for the type of education, develops thinking ability for solving problems in a broaden range based on 3-dimensional thinking of the user-oriented. Thus, with the hypothesis that utilization of 3D & 3-dimensional thinking helps to improve individual competency among equivocalness & complexity, which occur rapid development of technology for product design, It aimed to find out the effect of 3D-based method on techniques & speed of problem solving in a PDP. The experiment was conducted with the hypothesis 3-dimensional thinking & expression can enhance value, for a result from product design uses 3D, 3D related technology. For experiment, questionnaire was done by students in design high school to find out the role of 3D in the stage of ideation among PDP, which is important part for concept decision, significance & effect of PDP the students think. According to results from analysis, prototyping based on 3D in PDP has varied role depending on degree of difficulty. This implies 3D significantly influences ideation & stages based on prototyping are correlated with 3D & it has a role of recognition, preparation, consideration, conception, verification depending on degree of difficulty. Furthermore, the conclusion saying that stages related to 3D in a PDP induces to think idea without difficulty in a variety which influence creativity & students can feel satisfied & confident through actualization of the idea, was drawn. It is expected that application of the results will help to develop PDP optimized for performer’s thinking & behavior pattern based on 3-dimensional thinking among students.