Membrane targeting cationic antimicrobial peptides

Objectives Though antimicrobial peptides (AMPs) show great potential as novel antibiotics, therapeutic applications are hindered by their low stability, toxicity and high manufacturing cost. Various chemical modification strategies are employed to overcome these problems. However, chemical modifications often significantly increase the manufacturing cost of AMPs with only limited pharmacokinetic advantages. Therefore, we developed AMPs with enhanced stability and cell specificity that can be economically produced. Methods Peptides were designed by systematic amino acid arrangement without the incorporation of both non-natural amino acids and peptidomimetics. Antimicrobial activities were measured against Gram-positive bacteria, Gram-negative bacteria and fungi by MIC evaluation under both standard and physiologically relevant conditions. Cytotoxicity towards human cells was evaluated to verify selective antimicrobial activity. The antibacterial mechanism of the peptides was elucidated by β-galactosidase assay and scanning electron microscopy. Results Among the designed peptides, GNU6 and GNU7 showed potent antimicrobial activity against bacteria and fungi and maintained their activity in the presence of 150 mM NaCl and 10% serum. These peptides were not digested by exposure to trypsin, chymotrypsin and aureolysin for up to 12 h and showed potent antimicrobial activity against methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci. Moreover, they did not affect the viability of erythrocytes, keratinocytes and fibroblasts up to 128 mg/L. A membrane permeabilization assay and scanning electron microscopy analysis showed that GNU6 and GNU7 compromised membrane integrity and function in microorganisms. Conclusions This study suggests that GNU6 and GNU7 might overcome serious problems that currently prevent the clinical use of AMPs and be developed as novel antimicrobial agents.

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De novo generation of short antimicrobial peptides with enhanced stability and cell specificity

Membrane permeabilizing peptides (MPPs) are as ubiquitous as the lipid bilayer membranes they act upon. Produced by all forms of life, most membrane permeabilizing peptides are used offensively or defensively against the membranes of other organisms. Just as nature has found many uses for them, translational scientists have worked for decades to design or optimize membrane permeabilizing peptides for applications in the laboratory and in the clinic ranging from antibacterial and antiviral therapy and prophylaxis to anticancer therapeutics and drug delivery. Here, we review the field of membrane permeabilizing peptides. We discuss the diversity of their sources and structures, the systems and methods used to measure their activities, and the behaviors that are observed. We discuss the fact that “mechanism” is not a discrete or a static entity for an MPP but rather the result of a heterogeneous and dynamic ensemble of structural states that vary in response to many different experimental conditions. This ha...

Mechanistic Landscape of Membrane-Permeabilizing Peptides.

Contract cheating, where students use a third party to complete their assignments, is frequently reported to be increasing, presenting a threat to academic standards and quality. Many incidents involve payment of the third party, giving contract cheating a commercial aspect. This study synthesised findings from prior research to try and understand how common self-report of contract cheating is in Higher Education, and test whether it is increasing. It also sought to evaluate the quality of the research evidence which addresses those questions. 71 samples were identified from 65 studies, going back to 1978. These included 54514 participants. Contract cheating was self-reported by a historic average of 3.52 % of students, with evidence that this has increased in recent years; a positive relationship was found between time and the percentage of students admitting to contract cheating, and in samples from 2014 to present the figure is 15.7%, representing approximately 31 million students around the world. This increase may be due to an overall increase in self-reported cheating, rather than contract cheating specifically. Most samples were collected using designs which makes it likely that contract cheating is under-reported, for example using convenience sampling, with a very low response rate and without guarantees of anonymity for participants. Recommendations are made for future studies on academic integrity and contract cheating specifically.

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How Common Is Commercial Contract Cheating in Higher Education and Is It Increasing? A Systematic Review

52 Application of gee procedures for sample size calculations in repeated measures experiments

Academic cheating among nursing students

Purpose: In this study factors affecting job satisfaction and turnover intention of nurses were explored in the context of organizational culture, self- leadership, and empowerment. Methods: Participants were 286 nurses drawn from 3 general hospitals. Data were analyzed using t-test, one-way ANOVA, Pearson correlation, and hierarchial multiple regression with the SPSS/WIN 18.0 program. Results: Significant differences in job satisfaction and turnover intention were found according to organizational culture types. Significant positive correlations were found between self-leadership, empowerment, task oriented organizational culture, relationship oriented organizational culture, innovation oriented organizational culture and job satisfaction. On the other hand, significant negative relationships were found between empowerment, relationship oriented organizational culture, innovation oriented organizational culture and turnover intention. The factors that enhance job satisfaction were found to be higher innovation-oriented organizational culture. Lower turnover intention was shown to be positively associated with relationship- or innovation oriented organization culture. Conclusion: Innovation oriented organizational culture is needed in order to raise job satisfaction and reduce turnover intention of nurses.

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Effects of Organizational Culture, Self-Leadership and Empowerment on Job Satisfaction and Turnover Intention in General Hospital Nurses

PURPOSE The aim of this study was to compare the predictors of physical activity between urban and rural dwelling Korean older adults. METHODS This study was a cross-sectional descriptive survey. A self-report questionnaire or face to face interviews were used to collect data from 336 older adults (urban: 129, rural: 207) who visited public health centers or welfare centers in 2008. RESULTS About half of the participants (urban: 50.4%, rural: 47.3%) were classified as the minimally active group. Cognitive function (odds ratio [OR]=1.106, p=.004) and loneliness (OR=0.965, p=.044) were predicting factors for physical activity in rural elderly. Age (OR=0.326, p=.037), gender (OR=2.841, p=.021) and depression (OR=0.799, p<.001) were significant factors predicting physical activity in urban elders. CONCLUSION These findings provide information that is relevant in designing interventions to enhance physical activity in older adults. There is a need to develop effective mutifaceted physical activity interventions that include reducing psychological barriers such as depression, loneliness.

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Predictors of Physical Activity in Korean Older Adults: Distinction between Urban and Rural Areas

Purpose: This study was conducted to compare the degree of depression between men and women and to identify factors influencing their depression. Methods: Participants in this cross-sectional descriptive study were 263 persons over 65 years old (men: 103, women: 160). Data were collected through face to face interviews using questionnaires and were done in two urban areas in 2010. Research instruments utilized in this study were SGDS, MMSE-K, SRH, FILE, sleep pattern scale, family and friend support scale, and social support scale. Multivariate regression analysis was performed to identify factors influencing depression in elders. Results: The proportions of participants with depression were significantly different between men and women (52.4% vs. 67.5%). Regression model for depression in elderly men significantly accounted for 54%; disease stress (32%), economic stress (10%), perceived health status (4%), and family support, educational level, age, and hypertension. Regression model for depression in elderly women significantly accounted for 47%; disease stress (25%), perceived social loneliness (8%), friend support (5%), family stress (4%), and sleep satisfaction, and family support. Conclusion: Results demonstrate that depression is an important health problem for elders, and show gender differences for factors influencing depression. These results could be used in the developing depression prevention programs.

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[Gender difference in risk factors for depression in community-dwelling elders].

Cationic antimicrobial peptides (AMPs) have attracted a great deal of interest as a promising candidate for a novel class of antibiotics that might effectively treat recalcitrant infections caused by a variety of microbes that are resistant to currently available drugs. However, the AMPs are inherently limited in that they are inevitably susceptible to attacks by proteases generated by human and pathogenic microbes; this vulnerability severely hinders their pharmaceutical use in human therapeutic protocols. In this study, we report that a halocidin-derived AMP, designated HG1, was found to be resistant to proteolytic degradation. As a result of its unique structural features, HG1 proved capable of preserving its antimicrobial activity after incubation with trypsin, chymotrypsin, and human matrix metalloprotease 7 (MMP-7). Additionally, HG1 was observed to exhibit profound antimicrobial activity in the presence of fluid from human skin wounds or proteins extracted from the culture supernatants of Staphylococcus aureus and Pseudomonas aeruginosa. Greater understanding of the structural motifs of HG1 required for its protease resistance might provide feasible ways to solve the problems intrinsic to the development of an AMP-based antibiotic.

Seungmi Park

Papers

Academic cheating among nursing students

Effects of Organizational Culture, Self-Leadership and Empowerment on Job Satisfaction and Turnover Intention in General Hospital Nurses

Predictors of Physical Activity in Korean Older Adults: Distinction between Urban and Rural Areas

[Gender difference in risk factors for depression in community-dwelling elders].

Antimicrobial Activity of a Halocidin-Derived Peptide Resistant to Attacks by Proteases