The infectivity and behaviour of exsheathed and ensheathed Heterorhabditis megidis infective juveniles

The consequencesof sheath loss on infectivityand behaviourof infective juveniles (IJ) were investigatedin Heterorhabditis megidis. Ensheathed IJ were more infective, killing 32% of wax moth larvae, compared to 18% killed by exsheathed IJ. The percentage of time engaged in seven behavioural activitieswas recordedfor individuallystored IJ but no differenceswere found between exsheathed and ensheathed IJ. Immobility was the most common behavioural category exhibited by both exsheathed and ensheathed IJ, occupying one third of the observation time. Storage conditions affected the rate of exsheathment; 40% of IJ stored for 28 days in water in bulk (50 in 8 ml) exsheathed compared to only 23% of those stored individually (1 in 2 ml)

SMART Binary: Sample Size Calculation for Comparing Adaptive Interventions in SMART studies with Longitudinal Binary Outcomes

Sequential Multiple-Assignment Randomized Trials (SMARTs) play an increasingly important role in psychological and behavioral health research. This experimental approach enables researchers to answer scientific questions about how to sequence and match interventions to the unique, changing needs of individuals. A variety of sample size planning resources for SMART studies have been developed in recent years; these enable researchers to plan SMARTs for addressing different types of scientific questions. However, relatively limited attention has been given to planning SMARTs with binary (dichotomous) outcomes, which often require higher sample sizes relative to continuous outcomes. Existing resources for estimating sample size requirements for SMARTs with binary outcomes do not consider the potential to improve power by including a baseline measurement and/or multiple repeated outcome measurements. The current paper addresses this issue by providing sample size simulation code and approximate formulas for two-wave repeated measures binary outcomes (i.e., two measurement times for the outcome variable, before and after receiving the intervention). The simulation results agree well with the formulas. We also discuss how to use simulations to calculate power for studies with more than two outcome measurement occasions. The results show that having at least one repeated measurement of the outcome can substantially improve power under certain conditions.Comment: 73 pages, 2 figures, submitted to Multivariate Behavioral Researc

Combined magnetic and chemical patterning for neural architectures

In vitro investigation of neural architectures requires cell positioning. For that purpose, micro-magnets have been developed on silicon substrates and combined with chemical patterning to attract cells to adhesive sites and keep them there during incubation. We have shown that the use of micro-magnets allows to achieve a high filling factor (~90%) of defined adhesive sites in neural networks and prevents migration of cells during growth. This approach has great potential for neural interfacing by providing accurate and time-stable coupling with integrated nanodevices

Breast Milk, a Source of Beneficial Microbes and Associated Benefits for Infant Health

peer-reviewedHuman breast milk is considered the optimum feeding regime for newborn infants due to its ability to provide complete nutrition and many bioactive health factors. Breast feeding is associated with improved infant health and immune development, less incidences of gastrointestinal disease and lower mortality rates than formula fed infants. As well as providing fundamental nutrients to the growing infant, breast milk is a source of commensal bacteria which further enhance infant health by preventing pathogen adhesion and promoting gut colonisation of beneficial microbes. While breast milk was initially considered a sterile fluid and microbes isolated were considered contaminants, it is now widely accepted that breast milk is home to its own unique microbiome. The origins of bacteria in breast milk have been subject to much debate, however, the possibility of an entero-mammary pathway allowing for transfer of microbes from maternal gut to the mammary gland is one potential pathway. Human milk derived strains can be regarded as potential probiotics; therefore, many studies have focused on isolating strains from milk for subsequent use in infant health and nutrition markets. This review aims to discuss mammary gland development in preparation for lactation as well as explore the microbial composition and origins of the human milk microbiota with a focus on probiotic development

A dyad of lymphoblastic lysosomal cysteine proteases degrades the antileukemic drug L-asparaginase

l-Asparaginase is a key therapeutic agent for treatment of childhood acute lymphoblastic leukemia (ALL). There is wide individual variation in pharmacokinetics, and little is known about its metabolism. The mechanisms of therapeutic failure with l-asparaginase remain speculative. Here, we now report that 2 lysosomal cysteine proteases present in lymphoblasts are able to degrade l-asparaginase. Cathepsin B (CTSB), which is produced constitutively by normal and leukemic cells, degraded asparaginase produced by Escherichia coli (ASNase) and Erwinia chrysanthemi. Asparaginyl endopeptidase (AEP), which is overexpressed predominantly in high-risk subsets of ALL, specifically degraded ASNase. AEP thereby destroys ASNase activity and may also potentiate antigen processing, leading to allergic reactions. Using AEP-mediated cleavage sequences, we modeled the effects of the protease on ASNase and created a number of recombinant ASNase products. The N24 residue on the flexible active loop was identified as the primary AEP cleavage site. Sole modification at this site rendered ASNase resistant to AEP cleavage and suggested a key role for the flexible active loop in determining ASNase activity. We therefore propose what we believe to be a novel mechanism of drug resistance to ASNase. Our results may help to identify alternative therapeutic strategies with the potential of further improving outcome in childhood ALL