The biosynthesis of some bacterial and fungal polyketide metabolites

Methylmalonyl-CoA is a key building block in the biosynthesis of propionate derived polyketide metabolites. There are several known metabolic sources of methylmalonyl-CoA, e.g. succinyl-CoA (citric acid cycle), valine and isoleudne. An objective of this research was to investigate the role of the DNA base, thymine, as a source of methyhnalonyl-CoA in Streptomyces and hence probe the link between primary and secondary metabolism. Feeding key intermediates of the thymine and valine cataboHc pathways, i.e. [(^13)C(^2)H(_3)-methyl]-thymine, [(^13)C-methyl]- and [l-(613)c]-β- aminoisobutyric acid, sodium [3-(^13)C]-isobutyrate, sodium [(^13)C-methyl]- methacrylate and sodium [l-(^13)C]-methacrylate, to the monensin A producer, Streptomyces cinnamonensis, provided evidence of the reductive catabolism of thymine occurring in Streptomyces, analogous to mammals. The results also provided evidence which supports the existence of a novel deaminase enzyme mediating the transformation of β-aminoisobutyric add and methacrylyl-CoA. Cubensic add, isolated from Xylaria cubensis, is a long chain fungal metabolite possessing eight pendant methyl groups. Its biosynthesis from acetate and L-methionine units was demonstrated with the aid of feeding experiments, proving a classical fungal mode of assembly. Attempts to incorporate an advanced methylated precursor into cubensic add were unsuccessful. Biological intramolecular Diels-Alder reactions are implicated in the biosynthesis of a wide range of polyketide metabolites, e.g. nargenicin, solanapyrones. Attempts to demonstrate, by feeding an isotopically labelled precursor, an intramolecular Diels-Alder mechanism for the formation of the sbc membered ring in cytochalasin D, proved inconclusive. In the event, the precursor was degraded to acetate. This degradation was suppressed in the second attempt by the addition of a β-oxidation inhibitor, but still no incorporation of labelled precursor was evident

Around the table: Are multiple-touch surfaces better than single-touch for children's collaborative interactions?

This paper presents a classroom study that investigated the potential of using touch tabletop technology to support children's collaborative learning interactions. Children aged 7-10 worked in groups of three on a collaborative planning task in which they designed a seating plan for their classroom. In the single-touch condition, the tabletop surface allowed only one child to interact with the digital content at a time. In the multiple-touch condition, the children could interact with the digital content simultaneously. Results showed that touch condition did not affect the frequency or equity of interactions, but did influence the nature of children's discussion. In the multiple-touch condition, children talked more about the task; in the single-touch condition, they talked more about turn taking. We also report age and gender differences

In for a penny, in for a pound: methylphenidate reduces the inhibitory effect of high stakes on persistent risky choice

Methylphenidate (MPH) is a stimulant that increases extracellular levels of dopamine and noradrenaline. It can diminish risky decision-making tendencies in certain clinical populations. MPH is also used, without license, by healthy adults, but the impact on their decision-making is not well established. Previous work has found that dopamine receptor activity of healthy adults can modulate the influence of stake magnitude on decisions to persistently gamble after incurring a loss. In this study, we tested for modulation of this effect by MPH in 40 healthy human adults. In a double-blind experiment, 20 subjects received 20 mg of MPH, while 20 matched controls received a placebo. All were provided with 30 rounds of opportunities to accept an incurred loss from their assets or opt for a "double-or-nothing" gamble that would either avoid or double it. Rounds began with a variable loss that would double with every failed gamble until it was accepted, recovered, or reached a specified maximum. Probability of recovery on any gamble was low and ambiguous. Subjects receiving placebo gambled less as the magnitude of the stake was raised and as the magnitude of accumulated loss escalated over the course of the task. In contrast, subjects treated with MPH gambled at a consistent rate, well above chance, across all stakes and trials. Trait reward responsiveness also reduced the impact of high stakes. The findings suggest that elevated catecholamine activity by MPH can disrupt inhibitory influences on persistent risky choice in healthy adults

Using Physician Champions to Extend the Reach of the Let’s Go! 5-2-1-0 Obesity Prevention Program in Clinical Practice

ABSTRACT Introduction: There is limited evidence for large scale interventions to address childhood obesity. Let’s Go! is a Maine-based obesity prevention program that deploys a consistent message across multiple community settings to encourage children and families to make healthy choices. This report describes implementation of Let\u27s Go! in primary care offices. Methods: Consideration for physician champion recruitment included previous involvement with Let’s Go! and ensuring statewide geographic coverage. Champions received standardized training and became local leaders in obesity prevention and treatment. 13 champions engaged 99 practices at baseline; 71 practices were engaged all 4 years (2012-2015). Data were analyzed on 46 of 71 practices that completed surveys all 4 years, representing 226 clinicians. Results: Increases were observed in achievement of 3 basic criteria from 39% in 2012 to 87% in 2015 (p \u3c .001). Criteria include displaying program posters, documenting BMI, and discussing healthy behaviors at well-child visits. Discussion: The Let’s Go! strategy of engaging and supporting primary care practices resulted in widespread, standardized adoption of recommendations to prevent and treat childhood obesity. Conclusion: Physician champions have been effective in advancing childhood obesity interventions in Maine. This model could be applied to other public health problems wherever broad-based action is necessary. Keywords: children, obesity, prevention, primary care, physicia

The First Passage Probability of Intracellular Particle Trafficking

The first passage probability (FPP), of trafficked intracellular particles reaching a displacement L, in a given time t or inverse velocity S = t/L, can be calculated robustly from measured particle tracks, and gives a measure of particle movement in which different types of motion, e.g. diffusion, ballistic motion, and transient run-rest motion, can readily be distinguished in a single graph, and compared with mathematical models. The FPP is attractive in that it offers a means of reducing the data in the measured tracks, without making assumptions about the mechanism of motion: for example, it does not employ smoothing, segementation or arbitrary thresholds to discriminate between different types of motion in a particle track. Taking experimental data from tracked endocytic vesicles, and calculating the FPP, we see how three molecular treatments affect the trafficking. We show the FPP can quantify complicated movement which is neither completely random nor completely deterministic, making it highly applicable to trafficked particles in cell biology.Comment: Article: 13 pages, 8 figure

Let’s Go! 2022-2023 Educational Programs: A Realist Evaluation

Introduction: Let’s Go! is a community engagement initiative working to improve health behaviors that impact obesity. Let’s Go! provides educational programming for all medical learners and attending staff throughout Maine. A realist evaluation is a theory-led approach to evaluation that seeks to understand what works for whom, in what circumstances, and in what respects an intervention is more likely to succeed. This project used the realist evaluation framework to evaluate Let’s Go! educational programming in 2022-2023.https://knowledgeconnection.mainehealth.org/lambrew-retreat-2023/1030/thumbnail.jp

Management of massive splenomegaly.

A case demonstrating diagnostic and therapeutic rational for surgical management of massive splenomegaly

Biosimilar infliximab use in paediatric IBD

Background Biosimilar infliximab became available in the UK in 2015. Paediatric experience to date on its use is limited. We prospectively evaluated the safety and efficacy of biosimilar infliximab (Remsima) in two paediatric gastroenterology networks in patients with inflammatory bowel disease. Methods Prospective clinical data were collected from laboratory reports, electronic patient records and case notes of 40 patients starting Remsima for the first time. Disease activity scores together with blood and stool biomarkers were used to assess response. Results Our data set highlights that Remsima was associated with a significant clinical and biochemical improvement (p<0.01 or less for all parameters assessed) in Crohn’s disease post induction. There were no significant safety issues noted. The total cost saving was £47 800, representing a 38% reduction from originator. Conclusion We found that biosimilar infliximab is as effective as originator infliximab and its use is associated with significant cost savings

University for the Creative Arts staff research 2011

This publication brings together a selection of the University’s current research. The contributions foreground areas of research strength including still and moving image research, applied arts and crafts, as well as emerging fields of investigations such as design and architecture. It also maps thematic concerns across disciplinary areas that focus on models and processes of creative practice, value formations and processes of identification through art and artefacts as well as cross-cultural connectivity. Dr. Seymour Roworth-Stoke