Discovery, structure and biological activities of the cyclotides

The cyclotides are a family of small disulfide rich proteins that have a cyclic peptide backbone and a cystine knot formed by three conserved disulfide bonds. The combination of these two structural motifs contributes to the exceptional chemical, thermal and enzymatic stability of the cyclotides, which retain bioactivity after boiling. They were initially discovered based on native medicine or screening studies associated with some of their various activities, which include uterotonic action, anti-HIV activity, neurotensin antagonism, and cytotoxicity. They are present in plants from the Rubiaceae, Violaceae and Cucurbitaccae families and their natural function in plants appears to be in host defense: they have potent activity against certain insect pests and they also have antimicrobial activity. There are currently around 50 published sequences of cyclotides and their rate of discovery has been increasing over recent years. Ultimately the family may comprise thousands of members. This article describes the background to the discovery of the cyclotides, their structural characterization, chemical synthesis, genetic origin, biological activities and potential applications in the pharmaceutical and agricultural industries. Their unique topological features make them interesting from a protein folding perspective. Because of their highly stable peptide framework they might make useful templates in drug design programs, and their insecticidal activity opens the possibility of applications in crop protection.

Gene expression profiles in murine hematopoietic stem cells revisited: Analysis of cDNA libraries reveals high levels of translational and metabolic activities

Gene expression studies from hematopoietic stem cell (HSC) populations purified to variable degrees have defined a set of sternness genes. Unexpectedly, results also hinted toward a HSC chromatin poised in a wide-open state. With the aim of providing a robust tool for further studies into the molecular biology of HSCs, the studies herein describe the construction and comparative molecular analysis of A-phage cDNA libraries from highly purified HSCs that retained their long-term repopulating activities (long-term HSCs [LT-HSCs]) and from short-term repopulating HSCs that were largely depleted of these activities. Microarray analysis of the libraries confirmed the previous results but also revealed an unforeseen preferential expression of translation- and metabolism-associated genes in the LT-HSCs. Therefore, these data indicate that HSCs are quiescent only in regard of proliferative activities but are in a state of readiness to provide the metabolic and translational activities required after induction of proliferation and exit from the HSC pool.

Growth temperature of four Campylobacter jejuni strains influences their subsequent survival in food and water

Aim: To determine if Campylobacter jejuni grown at 37 and 42 degrees C have different abilities to survive on beef and chicken, and in water. Methods and Results: Beef, chicken and water were separately inoculated with four Camp. jejuni (two poultry and two beef) strains grown at 37 or 42 degrees C. The matrices were stored at similar to 4 degrees C and Camp. jejuni numbers were monitored over time by plate counts. On beef there was a greater decrease in number for two strains (P < 0.05; similar to 0.7 and 1.3 log CFU cm(-2)) grown at 37 degrees C as compared with 42 degrees C. By contrast on chicken there was a decrease in numbers for two strains (P < 0.05; similar to 1.3 and 1 log CFU g(-1)) grown at 42 degrees C as compared with 37 degrees C. In water there was a greater decrease in numbers for all strains (P < 0.05; similar to 3-5.3 log CFU ml(-1)) grown at 42 degrees C as compared with 37 degrees C. Conclusions: Growth temperature influences the survival of Camp. jejuni on food and in water. Significance and Impact of this study: Campylobacter jejuni survival studies need to consider growth temperature to avoid erroneous results. Campylobacter jejuni grown at 37 degrees C, the body temperature of humans and cattle, may represent a greater public health risk in water than those grown at 42 degrees C, the body temperature of poultry.

Skin delivery potency and antitumor activities of temozolomide ester prodrugs

Clinical trials have shown temozolomide to be an effective agent for treatment of malignant melanoma. In order to investigate its suitability for delivery via the skin, a series of temozolomide esters was synthesized as prodrugs. In vitro assays demonstrated temozolomide, temozolomide acid and the hexyl ester equi-effective against selected cancer cell lines. The susceptibility of the esters to enzyme hydrolysis and their effectiveness for application to the skin were investigated. The esters effectively diffuse through rat skin and the hexyl ester demonstrated profound potency for penetrating through skin. Topical application of 5% (w/v) hexyl ester in DMSO solution on a mouse model demonstrated a significant inhibition of tumor growth. These results suggest that temozolomide esters could be an effective alternative to temozolomide in the treatment of skin cancer. © 2005 Elsevier Ireland Ltd. All rights reserved.

The interactive effect of workplace stressors and mood on creativity and implementation activities: a dual level approach

This thesis analyses the impact of workplace stressors and mood on innovation activities. Based on three competitive frameworks offered by cognitive spreading activation theory, mood repair perspective, and mood-as-information theory, different sets of predictions are developed. These hypotheses are tested in a field study involving 41 R&D teams and 123 individual R&D workers, and in an experimental study involving 54 teams of students. Results of the field study suggest that stressors and mood interact to predict innovation activities in such a way that with increasing stressors a high positive ( or negative) mood is more detrimental to innovation activities than a low positive (or negative) mood, lending support to the mood repair perspective. These effects are found for both individuals and teams. In the experimental study this effect is replicated and potential boundary conditions and mediators are tested. In addition, this thesis includes the development of an instrument to assess creativity and implementation activities within the realm of task-related innovative performance.

A simultaneous examination of the effects of salesperson relationship-building activities and marketing activities on retail buyers' purchase decisions

Firms’ contemporary selling practices often not only demand that salespeople meet sales quotas, but also that they build strong, profitable relationships with customers. Given the belief that relationship-building activities can develop closer customer ties and improve sales performance, scholars have increasingly studied salesperson behaviors aimed at nurturing buyer-salesperson relations. However, while previous sales research has investigated the effects of a number of relational activities on performance outcomes in isolation, knowledge about their effectiveness in comparison to other important performance drivers is virtually absent. The present study provides some first theoretical and empirical insights into this research gap by simultaneously examining the role of specific salesperson relationship-building activities, and product-focused variables, in retail buyers’ new product purchase decisions. Following an extensive literature review, a two-part qualitative field study was conducted to explore salesperson relationship-building activities that are regarded as important by retail buyers. Two key relational behaviors were suggested by the customer-centric and retail industry-specific data; salesperson consultation (communication-based) and salesperson helping behavior (action-based). Drawing on this as well as extant literature, a conceptual framework was developed concerning the influences of these relationship-building activities and other product-focused factors on retail buyers’ new product acceptance. The study’s quantitative component contained a mail and web survey of U.S. retail buyers, resulting in a total dataset of 192 responses. After a comprehensive measure validation process, the theoretical hypotheses were tested using logistic regression analysis. Contrary to existing assertions, the results suggest that salesperson relationship-building activities themselves do not directly and/or indirectly influence purchase decisions, but instead can moderate the effects of product-focused determinants on retail buyers’ new product selections. Data on actual purchase decisions provide a high level of external validity to the findings. The study closes with a concluding discussion, including theoretical and managerial implications of the findings, limitations of the research, and directions for future inquiry.

Crazy animals and other activities for teaching young learners

This is a book for primary school teachers of English written by primary school teachers of English. It brings together the experience and expertise of teachers from around the world to provide a range of stimulating and exciting classroom activities for the primary classroom. There are 50 tried and trusted activities which have been refined and improved over the years by teachers working in diverse contexts and environments. Children will enjoy practising their English through these stimulating and motivating activities. Over 1 000 teachers were contacted and asked to send their favourite activities for teaching English to young learners. The most original and creative activities received were selected for this book. This book grew out of an Aston University - British Council research project called ‘Investigating Global Practices in Teaching English to Young Learners’.