Functional analysis of the leading malaria vaccine candidate AMA-1 reveals an essential role for the cytoplasmic domain in the invasion process

A key process in the lifecycle of the malaria parasite Plasmodium falciparum is the fast invasion of human erythrocytes. Entry into the host cell requires the apical membrane antigen 1 (AMA-1), a type I transmembrane protein located in the micronemes of the merozoite. Although AMA-1 is evolving into the leading blood-stage malaria vaccine candidate, its precise role in invasion is still unclear. We investigate AMA-1 function using live video microscopy in the absence and presence of an AMA-1 inhibitory peptide. This data reveals a crucial function of AMA-1 during the primary contact period upstream of the entry process at around the time of moving junction formation. We generate a Plasmodium falciparum cell line that expresses a functional GFP-tagged AMA-1. This allows the visualization of the dynamics of AMA-1 in live parasites. We functionally validate the ectopically expressed AMA-1 by establishing a complementation assay based on strain-specific inhibition. This method provides the basis for the functional analysis of essential genes that are refractory to any genetic manipulation. Using the complementation assay, we show that the cytoplasmic domain of AMA-1 is not required for correct trafficking and surface translocation but is essential for AMA-1 function. Although this function can be mimicked by the highly conserved cytoplasmic domains of P. vivax and P. berghei, the exchange with the heterologous domain of the microneme protein EBA-175 or the rhoptry protein Rh2b leads to a loss of function. We identify several residues in the cytoplasmic tail that are essential for AMA-1 function. We validate this data using additional transgenic parasite lines expressing AMA-1 mutants with TY1 epitopes. We show that the cytoplasmic domain of AMA-1 is phosphorylated. Mutational analysis suggests an important role for the phosphorylation in the invasion process, which might translate into novel therapeutic strategies.

Intercultural relations in a global world

The exploration of cross-cultural contact in a global and transnational world is essential for understanding how we can learn to live with difference in ways that go beyond tolerance. This book explores such contact in Euro-American/Australian societies as well as non-western multiethnic societies such as China, Malaysia, Indonesia and countries within Easter Europe. The contributors in this book expose the power relations underpinning such encounters as well as explore the possibilities for meaningful dialogue.

Medication administration via enteral tubes : a survey of nurses' practices

Aim: This article is a report of a study examining the practices of acute care nurses when administering medication via enteral tubes. Background. Administering medication via enteral tubes is predominantly a nursing responsibility across countries. It is important to establish what nurses actually do when giving enteral medication to inform policy and continuing education development.

Method: In 2007, a survey was conducted using a random sample of acute care nurses at two large metropolitan hospitals in Melbourne, Australia. There were 181 Registered Nurses who participated in the study; 92 (50Æ8%) practised in intensive care units, 52 (28Æ7%) in surgical areas, 30 (16Æ6%) in medical areas and 7 (3Æ9%) were from combined medical–surgical areas. The questionnaire was developed by the researchers and a pilot study was conducted in August 2006 to test reliability, face validity and user-friendliness of the tool.

Results: Nurses reported using a range of methods to verify enteral tube position prior to administering enteral medication; some were unreliable methods. A majority reported administering enteric-coated and slow or extended release forms of medication, and giving solid forms of medication when liquid form was available. Nearly all (96%) reported flushing a tube after giving medication, 28% before, and 12% always flushed between each medication.

Conclusion: Enteral medication administration practices are inconsistent. Some nurses are using unsafe practices and may therefore compromise patient care.

International collaborative project to compare and monitor the nutritional composition of processed foods

Background: Chronic diseases are the leading cause of premature death and disability in the world with overnutrition a primary cause of diet-related ill health. Excess energy intake, saturated fat, sugar, and salt derived from processed foods are a major cause of disease burden. Our objective is to compare the nutritional composition of processed foods between countries, between food companies, and over time.

Design: Surveys of processed foods will be done in each participating country using a standardized methodology. Information on the nutrient composition for each product will be sought either through direct chemical analysis, from the product label, or from the manufacturer. Foods will be categorized into 14 groups and 45 categories for the primary analyses which will compare mean levels of nutrients at baseline and over time. Initial commitments to collaboration have been obtained from 21 countries.

Conclusions: This collaborative approach to the collation and sharing of data will enable objective and transparent tracking of processed food composition around the world. The information collected will support government and food industry efforts to improve the nutrient composition of processed foods around the world.

Role of microstructure in the low cycle fatigue of multi-phase steels

The low cycle fatigue (LCF) behaviour of several commercially-produced multiphase steels was studied; including dual-phase (DP) and transformation induced plasticity (TRIP). In addition, a novel TRIP980 hybrid microstructure was examined that consisted of coarse ferrite grains along with low temperature bainite regions interspersed with retained austenite. Fully reversed strain controlled fatigue tests were conducted on the different steels to determine the cyclic stress response and strain to failure. The effects of the cyclic deformation on the microstructures were analysed using electron backscattered diffraction (EBSD) and X-ray diffraction (XRD). Results showed that the initial cyclic hardening behaviour and low cyclic softening ratio observed in the TRIP steels was not necessarily due to austenite to martensite transformation. Differences between the austenite transformation behaviour of the conventional and novel hybrid TRIP microstructures was related to the different surrounding phases and the size of the retained austenite.

Strain differences in coping behaviour, novelty seeking behaviour, and susceptibility to socially conditioned fear : a comparison between Wistar and Sprague Dawley rats

The aim of the current study was to generate socially conditioned fear in two different strains of rat (Wistar, W and Sprague Dawley, SD) using social conflict, in order to investigate whether the magnitude of the conditioned fear responses in each strain was related to behaviour exhibited prior to or during fear induction (i.e. social conflict). On day one of the study, all intruders were assessed for exploratory activity in a novel environment. Twenty four hours following the novel environment test the locomotor activity of the intruders was assessed, while they underwent a single familiarisation exposure to the arena in which the conflict was subsequently to occur in. Twenty-four hours following familiarisation, intruders underwent either a 10 min social conflict or sham conflict session. One day later we examined the response of the intruders when they were returned to the vacant resident's cage. Upon return to the conflict context, we examined the intruder's ultrasonic distress vocalisations and the extent to which locomotor activity was inhibited. We found that W rats displayed significantly more immobility (i.e. conditioned fear) upon return to context than did SD rats (p < 0.05). Importantly, we observed that the differences in the two strains behaviour upon return to context appeared to be related to their quite different patterns of coping behaviour. The results of the current study indicate that preclinical between-strain comparisons potentially have much to offer in regard to understanding the basis of resilience to social stress.