Characteristic structural features of indolicidin: effects of the cis-trans isomerism on its conformation

Indolicidin is an antimicrobial peptide showing a broad spectrum of antibacterial and antifungal activities, and according to the cis-trans isomerism of three Xaa-Pro peptide bonds, eight different stereoisomers could be distinguished for this peptide. As the cis-trans isomerism about the Xaa-Pro peptide bonds was not considered in previous studies, the structural features of distinct stereoisomeric forms were not characterized in detail, so far. In this theoretical study, the influences of cis-trans isomerism on the conformation of indolicidin were investigated, as well as the typical structural properties of each stereoisomer were determined, focusing on the secondary structures and intramolecular interactions. Based on the results derived from the molecular dynamics simulations, it could be concluded that the eight different stereoisomeric forms of indolicidin adopted characteristic conformational features. Nevertheless, the appearance of various turn structures and intramolecular interactions proved to be dependent on the cis or trans nature of Xaa-Pro peptide bonds, indicating the relevant role of Pro amino acids in determining the three-dimensional structure of this peptide

ATM, ATR and DNA-PKcs expressions correlate to adverse clinical outcomes in epithelial ovarian cancers

Background: Ataxia-telangiectasia mutated (ATM), ataxia-telangiectasia mutated and rad3 related (ATR) and DNA-dependent protein kinase catalytic sub-unit (DNA-PKcs) play critical roles in DNA damage response (DDR) by linking DNA damage sensing to DDR effectors that regulate cell cycle progression and DNA repair. Our objective was to evaluate if ATM, ATR and DNA-PKcs expressions could predict response to therapy and clinical outcome in epithelial ovarian cancers. Methods: We investigated ATM, ATR, and DNA-PKcs expressions in ovarian epithelial cancers [protein expression (n = 194 patients), mRNA expression (n = 156 patients)] and correlated to clinicopathological outcomes as well as expression of X-ray repair cross-complementing protein 1 (XRCC1), cell division cycle-45 (CDC45), cyclin-dependent kinase 1(CDK1) and Ki-67 in tumours. Results: High ATM protein expression was associated with serous cystadenocarcinomas (p = 0.021) and platinum resistance (p = 0.017). High DNA-PKcs protein expression was associated with serous cystadenocarcinomas (p = 0.006) and advanced stage tumours (p = 0.018). High ATM protein (p = 0.001), high ATM mRNA (p = 0.018), high DNA-PKcs protein (p = 0.002), high DNA-PKcs mRNA (p = 0.044) and high ATR protein (p = 0.001) expressions are correlated with poor ovarian cancer specific survival (OCSS). In multivariate Cox model, high DNA-PKcs (p = 0.006) and high ATR (p = 0.043) protein expressions remain independently associated with poor OCSS. Conclusions: ATM, ATR and DNA-PKcs expressions may have prognostic and predictive significances in epithelial ovarian cancer. General significance: The data presented here provides evidence that ATM, ATR and DNA-PKcs involved in DDR are not only promising biomarkers but are also rational targets for personalized therapy in ovarian cancer

Synthesis of multisubstituted pyrroles by nickel-catalyzed arylative cyclizations of N-tosyl alkynamides

The synthesis of multisubstituted pyrroles by the nickel-catalyzed reaction of N-tosylalkynamides with arylboronic acids is reported. These reactions are triggered by alkyne arylnickelation, followed by cyclization of the resulting alkenylnickel species onto the amide. The reversible E/Z isomerization of the alkenylnickel species is critical for cyclization. This method was applied to the synthesis of pyrroles that are precursors to BODIPY derivatives and a biologically active compound

Establishing consensus of position-specific predictors for elite youth soccer in England

Purpose: To construct a valid and reliable methodology for the development of position-specific predictors deemed appropriate for talent identification purposes within elite youth soccer in England. Method: N = 10 panel experts participated in a three-step modified e-Delphi poll to generate consensus on a series of generic youth player attributes. A follow-up electronic survey completed by coaches, scouts and recruitment staff (n = 99) ranked these attributes to specific player-positions. Results: A final list of 44 player attributes found consensus using the three-step modified e-Delphi poll. Findings indicated that player-positional attributes considered most important in the youth phase are more psychological and technical than physiological or anthropometric. Despite ‘hidden’ attributes (e.g., coachability, flair, versatility, and vision) finding consensus on the e-Delphi poll, there was no evidence to support these traits when associated with a specific playing position. Conclusion: For those practitioners responsible for talent recruitment, our findings may provide greater understanding of the multiple attributes required for some playing positions. However, further ecological research is required to assess the veracity of our claims

Engineering Colloidal Metal-Semiconductor Nanorods Hybrid Nanostructures for Photocatalysis

Comprehensive Summary Emerging engineering strategies of colloidal metal-semiconductor nanorod hybrid nanostructures spanning from type, size, dimension, and location of both metal nanoparticles and semiconductors, co-catalyst, band gap structure, surface ligand to hole scavenger are elaborated symmetrically to rationalize the design of this type of intriguing materials for efficient photocatalytic applications. This article is protected by copyright. All rights reserved

Hypermedia learning and prior knowledge: Domain expertise vs. system expertise

Prior knowledge is often argued to be an important determinant in hypermedia learning, and may be thought of as including two important elements: domain expertise and system expertise. However, there has been a lack of research considering these issues together. In an attempt to address this shortcoming, this paper presents a study that examines how domain expertise and system expertise influence students’ learning performance in, and perceptions of, a hypermedia system. The results indicate that participants with lower domain knowledge show a greater improvement in their learning performance than those with higher domain knowledge. Furthermore, those who enjoy using the Web more are likely to have positive perceptions of non-linear interaction. Discussions on how to accommodate the different needs of students with varying levels of prior knowledge are provided based on the results