De Novo Design and Synthesis of Ultra-Short Peptidomimetic Antibiotics Having Dual Antimicrobial and Anti-Inflammatory Activities

Ravichandran N. Murugan, Mija Ahn, Eunha Hwang, Ji-Hyung Seo, Chaejoon Cheong, Jeong Kyu Bang, Division of Magnetic Resonance, Korea Basic Science Institute, Ochang, Chung-Buk, Republic of KoreaBinu Jacob, Song Yub Shin, Department of Bio-Materials, Graduate School and Department of Cellular and Molecular Medicine, School of Medicine, Chosun University, Gwangju, Republic of KoreaHoik Sohn, Department of Chemistry and Biochemistry, University of Texas at Austin, Austin, Texas, United States of AmericaHyo-Nam Park, Jae-Kyung Hyun, Division of Electron Microscopic Research, Korea Basic Science Institute, Daejeon, Republic of KoreaEunjung Lee, Ki-Woong Jeong, Yangmee Kim, Department of Bioscience and Biotechnology, Institute of SMART Biotechnology, Konkuk University, Seoul, Republic of KoreaKy-Youb Nam, Bioinformatics and Molecular Design Research Center, Yonsei University Research Complex, Seoul, Republic of KoreaBackground: Much attention has been focused on the design and synthesis of potent, cationic antimicrobial peptides (AMPs) that possess both antimicrobial and anti-inflammatory activities. However, their development into therapeutic agents has been limited mainly due to their large size (12 to 50 residues in length) and poor protease stability.-- Methodology/Principal Findings: In an attempt to overcome the issues described above, a set of ultra-short, His-derived antimicrobial peptides (HDAMPs) has been developed for the first time. Through systematic tuning of pendant hydrophobic alkyl tails at the N(π)- and N(τ)-positions on His, and the positive charge of Arg, much higher prokaryotic selectivity was achieved, compared to human AMP LL-37. Additionally, the most potent HDAMPs showed promising dual antimicrobial and anti-inflammatory activities, as well as anti–methicillin-resistant Staphylococcus aureus (MRSA) activity and proteolytic resistance. Our results from transmission electron microscopy, membrane depolarization, confocal laser-scanning microscopy, and calcein-dye leakage experiments propose that HDAMP-1 kills microbial cells via dissipation of the membrane potential by forming pore/ion channels on bacterial cell membranes. -- Conclusion/Significance: The combination of the ultra-short size, high-prokaryotic selectivity, potent anti-MRSA activity, anti-inflammatory activity, and proteolytic resistance of the designed HDAMP-1, -3, -5, and -6 makes these molecules promising candidates for future antimicrobial therapeutics.This work was supported in part by the Korea Basic Science Institute's research program grants T33418 (J.K.B) and T33518 (J-k.H.), and the Korea Research Foundation, funded by the Korean Government (KRF-2011-0009039 to S.Y.S.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.ChemistryBiochemistryEmail: [email protected] (JKB)Email: [email protected] (SYS

Expertise in EFL textbook evaluation

This thesis reports on a study of expertise in English as a foreign language (EFL) textbook evaluation. So far, studies in the area of EFL textbook evaluation have focused on what evaluators should do, rather than what they actually do. However, this thesis describes the procedures used in practice by a group of teacher evaluators in terms of what they focused on and their manner of doing so, in their actual evaluation of an EFL textbook. The study was conducted in the Korean high school setting, where school teachers are required to choose from among the 'authorised' EFL textbooks approved by the Ministry of Education. The primary heuristic involved in the study was the concept of 'expertise' . The attempt was therefore made to distinguish between the textbook evaluation approach of the research subjects who were conceptualised as, on the one hand, 'expert' evaluators and, on the other, those thought of as 'non-experts'. Thus, twelve Korean EFL school teachers were chosen to evaluate one of the authorised EFL textbooks, and data gathered concerning their evaluations by means of concurrent verbalisation, i.e., the research subjects were audio-taped while providing 'think-aloud' accounts of their evaluation procedures. A 'judgment group', comprising a panel of personnel with distinguished records in the areas of textbook evaluation and production in the Korean context, then examined the data from the evaluations and made judgements on their quality in terms of whether they were considered 'expert', 'non-expert' or 'in- between' the two. The transcripts of the evaluation session tapes were coded using a 'grounded' approach, in order to distinguish the features attaching to each of the three main categories of evaluators. The analysis indicated that the expert evaluators evaluated at a much deeper level than the non-experts, as evinced by what they considered, what their priorities were, and the nature of the cognitive activities they used. The study is seen to have pedagogic implications for both textbook development and teacher development, as well as for the development of a research framework that bridges a current gap in textbook evaluation studies. It is also seen as contributing to widening the potential for the application of an expertise perspective within applied linguistics in general.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Design and implementation of S-compiler interpass

Typescript (photocopy).Digitized by Kansas Correctional Industrie

Understanding Gender Differences in Students’ Perceptions of Competency Certification for Enhancing Sustainability in Higher Education

This study of 1780 college students in Korea explored gender differences in perceptions of competency certification programs in order to enhance sustainability in higher education. Structural equation modeling explained the optimal validity of the two-factor structure of perceptions between female and male students, and the structural relations between the two factors of competency were invariant across gender groups. A significant difference in latent means was found as well. The findings suggest that, for sustainable development, universities should develop systematic competency certification policies to accommodate students’ needs, as well as those of society, and help bridge the gender gap in the job market

Isolation of a polyethylene-degrading bacterium, Acinetobacter guillouiae, using a novel screening method based on a redox indicator

Plastic, a polymer synthesized from petrochemicals, is used worldwide. However, natural degradation of plastic is difficult, causing environmental pollution, with microplastics posing a serious threat to human health. In this study, we aimed to use a new screening method based on the oxidation-reduction indicator, 2,6-dichlorophenolindophenol, to isolate a polyethylene-degrading bacterium, Acinetobacter guillouiae, from insect larvae. Plastic-degrading strains are identified by the color change in the redox indicator from blue to colorless as plastic metabolism occurs. Polyethylene biodegradation by A. guillouiae was verified through weight loss, surface erosion, physiological evidence, and chemical changes on the plastic surface. In addition, we analyzed the characteristics of hydrocarbon metabolism in polyethylene-degrading bacteria. Results suggested that alkane hydroxylation and alcohol dehydrogenation were key steps in polyethylene degradation. This novel screening method will pave the way for high-throughput screening of polyethylene-degrading microorganisms and extending its application to other types of plastics may potentially address plastic pollution

Survey on Contamination of Fusarium Mycotoxins in 2011-harvested Rice and Its By-products from Rice Processing Complexes in Korea

To investigate Fusarium mycotoxin contamination in rice samples from rice processing complexes (RPCs), paddy rice and rice-milling products such as husks, brown rice, blue-tinged rice, broken rice, rice bran, discolored rice, and polished rice were collected from nationwide in 2012. Three hundred seventy one samples of rice and its by-products were analyzed for three trichothethenes including nivalenol (NIV), deoxynivalenol (DON), and zearalenone (ZEA) by LC/MS. Discolored rice samples were found to have the highest contamination of DON, NIV or ZEA, followed by broken rice. Polished rice samples were largely free from mycotoxins, except three samples which were contaminated with NIV or DON at safety level. The rice byproduct samples were contaminated at higher level and frequencies than polished rice samples

A step forward:Investigating expertise in materials evaluation

This article reports on a study investigating the textbook evaluation techniques of novice and experienced teachers, which was conducted by the Language Teaching Expertise Research Group (or LATEX) within Lancaster University's Department of Linguistics and English Language. Three ELT teachers were chosen to evaluate the student and teacher editions of a newly-released ELT textbook using the technique of concurrent verbalization. The results of the research add to the growing body of knowledge on expertise, providing insight into the differences between the teachers with respect to their various evaluation strategies. They also point to implications for the development of teacher education and training

Structural basis for recognition of Emi2 by Polo-like kinase 1 and development of peptidomimetics blocking oocyte maturation and fertilization

Photograph of a scene at the Philbrook Museum of Art

Molecular Basis for Unidirectional Scaffold Switching of Human Plk4 in Centriole Biogenesis

Polo-like kinase 4 (Plk4) is a key regulator of centriole duplication, an event critical for the maintenance of genomic integrity. Here we showed that Plk4 relocalizes from the inner Cep192 ring to the outer Cep152 ring as newly recruited Cep152 assembles around the Cep192-encircled daughter centriole. Crystal structure analyses revealed that Cep192 - and Cep152-derived peptides bind the cryptic polo box (CPB) of Plk4 in opposite orientations and in a mutually exclusive manner. The Cep152-peptide bound to the CPB markedly better than the Cep192-peptide and effectively snatched the CPB away from a preformed CPB–Cep192-peptide complex. A cancer-associated Cep152 mutation impairing the Plk4 interaction induced defects in procentriole assembly and chromosome segregation. Thus, Plk4 is intricately regulated in time and space through ordered interactions with two distinct scaffolds, Cep192 and Cep152, and a failure in this process may lead to human cancer