Molecular Design, Functional Characterization and Structural Basis of a Protein Inhibitor Against the HIV-1 Pathogenicity Factor Nef

Increased spread of HIV-1 and rapid emergence of drug resistance warrants development of novel antiviral strategies. Nef, a critical viral pathogenicity factor that interacts with host cell factors but lacks enzymatic activity, is not targeted by current antiviral measures. Here we inhibit Nef function by simultaneously blocking several highly conserved protein interaction surfaces. This strategy, referred to as “wrapping Nef”, is based on structure-function analyses that led to the identification of four target sites: (i) SH3 domain interaction, (ii) interference with protein transport processes, (iii) CD4 binding and (iv) targeting to lipid membranes. Screening combinations of Nef-interacting domains, we developed a series of small Nef interacting proteins (NIs) composed of an SH3 domain optimized for binding to Nef, fused to a sequence motif of the CD4 cytoplasmic tail and combined with a prenylation signal for membrane association. NIs bind to Nef in the low nM affinity range, associate with Nef in human cells and specifically interfere with key biological activities of Nef. Structure determination of the Nef-inhibitor complex reveals the molecular basis for binding specificity. These results establish Nef-NI interfaces as promising leads for the development of potent Nef inhibitors

Developing a clinical presentation dental education model and a pilot test

Introduction Accurate clinical decision-making of dentists should be based on their knowledge and experience. In the past 10 years, interest in competency-based dentistry education has rapidly increased, but there has been little attention paid to methods of improving dental education competency. The purpose of this study was to develop a clinical presentation education model that provides opportunities for students to practice problem-solving from the moment they greet the patient so that students can obtain the practical experience of competency-based education and the effectiveness of this model can be confirmed through pilot test. Methods This article is divided two parts: First, developing the clinical presentation dental education model (CPDEM) and Second, a pilot study adopted CPDEM. To confirm the effectiveness of this model, the students' satisfaction, their perception of self-achievement were analysed. Results Clinical presentation dental education model has been developed to provide practice-related education experience and provide linkage between basic science and clinical science. The result of applying this education model to 10 students as a pilot test was shown an overall high satisfaction level. In addition, self-achievement students' reported of all intended competencies was higher than for non-participating students of this model. Conclusions This study focuses on practical education centring on clinical presentation. This model could get a meaningful and realistic experiences through the practice using clinical presentation of patients, use their metacognition for organizing and memorizing the patient's case by using concept map. It can be used as a future instructional method to enhance students' competency.N

Effects of Bt maize on the herbivore Spodoptera littoralis (Lepidoptera: Noctuidae) and the parasitoid Cotesia marginiventris (Hymenoptera: Braconidae)

Recent studies have shown that transgenic insect resistant plants can have negative effects on non-target herbivores as well as on beneficial insects. The studyof tritrophic interactions gives insight into the complex mechanisms of food webs in the field and can easily be incorporated into a tiered risk assessment framework. We investigated the effects of transgenic maize (Zea mays) expressing insecticidal proteins derived from Bacillus thuringiensis (Bt maize) on Spodoptera littoralis, a non-target herbivore, and on the hymenopteran parasitoid Cotesia marginiventris. In a laboratory study, S. littoralis larvae were reared for their whole lifespan on a mixture of leaves and stems from 2–4-week old Bt maize plants. S. littoralis survival, developmental times and larval weights were significantly affected by Bt maize diet. However, adult moths, which survived development on Bt maize, were the same size as the adults from the control group. C. marginiventris survival, developmental times and cocoon weights were significantly negatively affected if their S. littoralis host larva had been fed Bt maize. ELISA tests confirmed that S. littoralis larvae ingest high amounts of Cry1A(b) toxin while feeding on Bt maize. In S. littoralis pupae and in C. marginiventris cocoon silk, only traces of the toxin could be detected. No toxin was found in S. littoralis and C. marginiventris adults. Thus the toxin is not accumulating in the trophic levels and in fact appears to be excreted. Our results suggest that the effects on C. marginiventris when developing in susceptible S. littoralis larvae are indirect (host mediated). The biological relevance of those results and the significance of this study in risk assessment are discussed