315 research outputs found

    Development and Evaluation of an Undergraduate Science Communication Module

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    This paper describes the design and evaluation of an undergraduate final year science communication module for the Science Faculty at the University of East Anglia. The module focuses specifically on science communication and aims to bring an understanding of how science is disseminated to the public. Students on the module are made aware of the models surrounding science communication and investigate how the science culture interfaces with the public. During the module they learn how to adapt science concepts for different audiences and how to talk confidently about science to a lay-audience. Student motivation for module choice centres on the acquisition of transferable skills and students develop these skills through designing, running and evaluating a public outreach event at a school or in a public area. These transferable skills acquired include communication, interaction with different organisations such as museums and science centres, developing understanding of both the needs of different audiences and the importance of time management. They also develop skills relating to self-reflection and how to use this as a tool for future self development. The majority of students completing the module go on to further study, either a PhD, MSc or teacher training. The module can be sustained in its present formed if capped at 40 students, however it is recognised that to increase cohort size, further investment of faculty time and resources would be required

    Illuminating the bacterial microbiome of Australian ticks with 16S and Rickettsia-specific next-generation sequencing

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    Next-generation sequencing (NGS) studies show that mosquito and tick microbiomes influence the transmission of pathogens, opening new avenues for vector-borne pathogen control. Recent microbiological studies of Australian ticks highlight fundamental knowledge gaps of tick-borne agents. This investigation explored the composition, diversity and prevalence of bacteria in Australian ticks (n = 655) from companion animals (dogs, cats and horses). Bacterial 16S NGS was used to identify most bacterial taxa and a Rickettsia-specific NGS assay was developed to identify Rickettsia species that were indistinguishable at the V1-2 regions of 16S. Sanger sequencing of near full-length 16S was used to confirm whether species detected by 16S NGS were novel. The haemotropic bacterial pathogens Anaplasma platys, Bartonella clarridgeiae, “Candidatus Mycoplasma haematoparvum” and Coxiella burnetii were identified in Rhipicephalus sanguineus (s.l.) from Queensland (QLD), Western Australia, the Northern Territory (NT), and South Australia, Ixodes holocyclus from QLD, Rh. sanguineus (s.l.) from the NT, and I. holocyclus from QLD, respectively. Analysis of the control data showed that cross-talk compromises the detection of rare species as filtering thresholds for less abundant sequences had to be applied to mitigate false positives. A comparison of the taxonomic assignments made with 16S sequence databases revealed inconsistencies. The Rickettsia-specific citrate synthase gene NGS assay enabled the identification of Rickettsia co-infections with potentially novel species and genotypes most similar (97.9–99.1%) to Rickettsia raoultii and Rickettsia gravesii. “Candidatus Rickettsia jingxinensis” was identified for the first time in Australia. Phylogenetic analysis of near full-length 16S sequences confirmed a novel Coxiellaceae genus and species, two novel Francisella species, and two novel Francisella genotypes. Cross-talk raises concerns for the MiSeq platform as a diagnostic tool for clinical samples. This study provides recommendations for adjustments to Illuminaʼs 16S metagenomic sequencing protocol that help track and reduce cross-talk from cross-contamination during library preparation. The inconsistencies in taxonomic assignment emphasise the need for curated and quality-checked sequence databases

    A new look at energy release rates for quasistatically propagating cracks in inelastic materials

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    A mapping technique is used to derive an integral expression for the energy release rate for a quasistatically propagating crack. The derivation does not depend on any assumptions in regard to the contitutive behavior of the material. It leads to a contour integral around the crack tip, plus an area integral over the region enclosed by this contour. Only the stress and displacement fields appear in the integrands. Although for stationary crack solutions known to the authors the area integral is not convergent, for propagating crack solutions in elastoplastic material, the integrals are convergent, and lead to zero energy release rate. This confirms conclusions by Rice from an independent point of view.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42773/1/10704_2004_Article_BF00012388.pd

    TRIM33 switches off Ifnb1 gene transcription during the late phase of macrophage activation

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    Despite its importance during viral or bacterial infections, transcriptional regulation of the interferon-β gene (Ifnb1) in activated macrophages is only partially understood. Here we report that TRIM33 deficiency results in high, sustained expression of Ifnb1 at late stages of toll-like receptor-mediated activation in macrophages but not in fibroblasts. In macrophages, TRIM33 is recruited by PU.1 to a conserved region, the Ifnb1 Control Element (ICE), located 15 kb upstream of the Ifnb1 transcription start site. ICE constitutively interacts with Ifnb1 through a TRIM33-independent chromatin loop. At late phases of lipopolysaccharide activation of macrophages, TRIM33 is bound to ICE, regulates Ifnb1 enhanceosome loading, controls Ifnb1 chromatin structure and represses Ifnb1 gene transcription by preventing recruitment of CBP/p300. These results characterize a previously unknown mechanism of macrophage-specific regulation of Ifnb1 transcription whereby TRIM33 is critical for Ifnb1 gene transcription shutdown

    Associations of Maternal Early-Pregnancy Glucose Concentrations With Placental Hemodynamics, Blood Pressure, and Gestational Hypertensive Disorders

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    BACKGROUND: Gestational diabetes mellitus is associated with increased risks of gestational hypertension and preeclampsia. We hypothesized that high maternal glucose concentrations in early pregnancy are associated with adverse placental adaptations and subsequently altered uteroplacental hemodynamics during pregnancy, predisposing to an increased risk of gestational hypertensive disorders. METHODS: In a population-based prospective cohort study from early pregnancy onwards, among 6,078 pregnant women, maternal early-pregnancy non-fasting glucose concentrations were measured. Mid and late pregnancy uterine and umbilical artery resistance indices were assessed by Doppler ultrasound. Maternal blood pressure was measured in early, mid, and late pregnancy and the occurrence of gestational hypertensive disorders was assessed using hospital registries. RESULTS: Maternal early-pregnancy glucose concentrations were not associated with mid or late pregnancy placental hemodynamic markers. A 1 mmol/l increase in maternal early-pregnancy glucose concentrations was associated with 0.71 mm Hg (95% confidence interval 0.22-1.22) and 0.48 mm Hg (95% confidence interval 0.10-0.86) higher systolic and diastolic blood pressure in early pregnancy, respectively, but not with blood pressure in later pregnancy. Also, maternal glucose concentrations were not associated with the risks of gestational hypertension or preeclampsia. CONCLUSIONS: Maternal early-pregnancy non-fasting glucose concentrations within the normal range are associated with blood pressure in early pregnancy, but do not seem to affect placental hemodynamics and the risks of gestational hypertensive disorders

    Design and rationale of the Cardiovascular Health and Text Messaging (CHAT) Study and the CHAT-Diabetes Mellitus (CHAT-DM) Study: two randomised controlled trials of text messaging to improve secondary prevention for coronary heart disease and diabetes

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    INTRODUCTION:Mobile health interventions have the potential to promote risk factor management and lifestyle modification, and are a particularly attractive approach for scaling across healthcare systems with limited resources. We are conducting two randomised trials to evaluate the efficacy of text message-based health messages in improving secondary coronary heart disease (CHD) prevention among patients with or without diabetes. METHODS AND ANALYSIS:The Cardiovascular Health And Text Messaging (CHAT) Study and the CHAT-Diabetes Mellitus (CHAT-DM) Study are multicentre, single-blind, randomised controlled trials of text messaging versus standard treatment with 6 months of follow-up conducted in 37 hospitals throughout 17 provinces in China. The intervention group receives six text messages per week which target blood pressure control, medication adherence, physical activity, smoking cessation (when appropriate), glucose monitoring and lifestyle recommendations including diet (in CHAT-DM). The text messages were developed based on behavioural change techniques, using models such as the information-motivation-behavioural skills model, goal setting and provision of social support. A total sample size of 800 patients would be adequate for CHAT Study and sample size of 500 patients would be adequate for the CHAT-DM Study. In CHAT, the primary outcome is the change in systolic blood pressure (SBP) at 6 months. Secondary outcomes include a change in proportion of patients achieving a SBP <140 mm Hg, low-density lipoprotein cholesterol (LDL-C), physical activity, medication adherence, body mass index (BMI) and smoking cessation. In CHAT-DM, the primary outcome is the change in glycaemic haemoglobin (HbA1C) at 6 months. Secondary outcomes include a change in the proportion of patients achieving HbA1C<7%, fasting blood glucose, SBP, LDL-C, BMI, physical activity and medication adherence. ETHICS AND DISSEMINATION:The central ethics committee at the China National Center for Cardiovascular Disease and the Yale University Institutional Review Board approved the CHAT and CHAT-DM studies. Results will be disseminated via usual scientific forums including peer-reviewed publications. TRIAL REGISTRATION NUMBER:CHAT (NCT02888769) and CHAT-DM (NCT02883842); Pre-results.Xiqian Huo, Erica S Spatz, Qinglan Ding, Paul Horak, Xin Zheng, Claire Masters ... et al

    Phenomenology of the Lense-Thirring effect in the Solar System

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    Recent years have seen increasing efforts to directly measure some aspects of the general relativistic gravitomagnetic interaction in several astronomical scenarios in the solar system. After briefly overviewing the concept of gravitomagnetism from a theoretical point of view, we review the performed or proposed attempts to detect the Lense-Thirring effect affecting the orbital motions of natural and artificial bodies in the gravitational fields of the Sun, Earth, Mars and Jupiter. In particular, we will focus on the evaluation of the impact of several sources of systematic uncertainties of dynamical origin to realistically elucidate the present and future perspectives in directly measuring such an elusive relativistic effect.Comment: LaTex, 51 pages, 14 figures, 22 tables. Invited review, to appear in Astrophysics and Space Science (ApSS). Some uncited references in the text now correctly quoted. One reference added. A footnote adde

    Virtual discovery of melatonin receptor ligands to modulate circadian rhythms

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    The neuromodulator melatonin synchronizes circadian rhythms and related physiological functions through the actions of two G-protein-coupled receptors: MT1 and MT2. Circadian release of melatonin at night from the pineal gland activates melatonin receptors in the suprachiasmatic nucleus of the hypothalamus, synchronizing the physiology and behaviour of animals to the light–dark cycle1–4. The two receptors are established drug targets for aligning circadian phase to this cycle in disorders of sleep5,6 and depression1–4,7–9. Despite their importance, few in vivo active MT1-selective ligands have been reported2,8,10–12, hampering both the understanding of circadian biology and the development of targeted therapeutics. Here we docked more than 150 million virtual molecules to an MT1 crystal structure, prioritizing structural fit and chemical novelty. Of these compounds, 38 high-ranking molecules were synthesized and tested, revealing ligands with potencies ranging from 470 picomolar to 6 micromolar. Structure-based optimization led to two selective MT1 inverse agonists—which were topologically unrelated to previously explored chemotypes—that acted as inverse agonists in a mouse model of circadian re-entrainment. Notably, we found that these MT1-selective inverse agonists advanced the phase of the mouse circadian clock by 1.3–1.5 h when given at subjective dusk, an agonist-like effect that was eliminated in MT1- but not in MT2-knockout mice. This study illustrates the opportunities for modulating melatonin receptor biology through MT1-selective ligands and for the discovery of previously undescribed, in vivo active chemotypes from structure-based screens of diverse, ultralarge libraries. © 2020, The Author(s), under exclusive licence to Springer Nature Limited
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