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Grasses accumulate large amounts of silicon (Si) which acts as a highly effective physical defence against insect herbivory, however recent evidence shows that Si supplementation also modifies plant secondary metabolite concetrations. Changes in plant secondary metabolites concentrations can have cascading effects on higher trophic levels, such as parasitoids, as they are dependent on the host herbivore for growth and development. However, relatively little is known about how Si application affects higher trophic levels. We examined the effects of Si addition on alkaloid content in leaves of Phalaris aquatica (Poaceae) and the effect on interactions between an aphid (Rhopalosiphum padi) and its parasitoid (Aphidius colemani). Si supplementation had no effect on aphid abundance or parasitism rate. Adult aphids, aphid mummies (parasitised aphids) and the emergent parasitoids were, however, significantly smaller on Si+ plants. Parasitoid traits (size and emergence) were correlated with aphid mummy size. Si addition reduced parasitoid emergence rate and size due to reduced host mummy size, in addition, significantly fewer females emerged from mummies on Si+ plants. Aphid infestation significantly altered alkaloids concentrations, reducing gramine by 80% while increasing tryptamine by 91% in Si- plants. Si addition reduced aphid-induced tryptamine concentrations by 64% and increased 5-MeO-tryptamine by over 800% in control and 142% in aphid infested plants. Our results show that while Si addition has modest impacts on the herbivore, it significantly alters secondary metabolites and has stronger effects on the higher trophic level through changes in the quality of the parasitised host.

This paper highlights both an overreliance on legal perspectives in the study of paradiplomacy at the expense of more dynamic understandings of agency, and also the affective force of waiting and o...

Background and aims Many undergraduate medical curricula include reflective practice sessions based on traditional Balint-groups. Those sessions can help students to acknowledge that experiencing ‘negative’ feelings in relation to patients is normal and may contain important information about the clinical encounter. They may also help to protect students from some of the emotional challenges of studying medicine. The Edinburgh University scheme provides all students in their first clinical year with two dedicated reflective practice sessions. Here we report on experience of the first two years. Methods Students’ attitudes to the sessions were ascertained using a questionnaire, and views of the group leaders were assessed using a questionnaire and through informal verbal and email discussions. Practical difficulties were recorded as they arose. Results Students generally rated the sessions positively with regard to exploring relationships and self-reflection, and they found the sessions interesting and helpful. The sessions did not seem to affect career choice. The free-text comments suggested four positive themes and four areas for future modification. Conclusion We have succeeded in providing all undergraduate students with an opportunity to take part in a reflective practice. We have highlighted aspects which have been successful and suggested future improvements.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The neuroactive mycotoxin lolitrem B causes a neurological syndrome in grazing livestock resulting in hyperexcitability, muscle tremors, ataxia and, in severe cases, clonic seizures and death. To define the effects of the major toxin lolitrem B in the brain, a functional metabolomic study was undertaken in which motor coordination and tremor were quantified and metabolomic profiling undertaken to determine relative abundance of both toxin and key neurotransmitters in various brain regions in male mice. Marked differences were observed in the duration of tremor and coordination between lolitrem B pathway members, with some showing protracted effects and others none at all. Lolitrem B was identified in liver, kidney, cerebral cortex and thalamus but not in brainstem or cerebellum which were hypothesised previously to be the primary site of action. Metabolomic profiling showed significant variation in specific neurotransmitter and amino acid profiles over time. This study demonstrates accumulation of lolitrem B in the brain, with non-detectable levels of toxin in the brainstem and cerebellum, inducing alterations in metabolites such as tyrosine, suggesting a dynamic catecholaminergic response over time. Temporal characterisation of key pathways in the pathophysiological response of lolitrem B in the brain were also identified.

Recent research into the benefits of feeding pomegranate (Punica granatum L.) peels or extracts to dairy cattle has suggested these supplements may increase the health and productivity of these animals. However, in Victoria, Australia, several cattle died after consuming large amounts of pomegranate fruit, causing suspicion about the safety of pomegranates to cattle. An in vitro bioassay mediated approach was used to purify and identify metabolites from a crude extract of pomegranate fruit obtained from the affected farm. The metabolites that are most likely to cause cytotoxicity to bovine kidney epithelial cells (MDBK) were identified as gallic acid (IC50 41.2 ± 19.0 μg/mL), ellagic acid, and punicalagin (IC50 314.1 ± 110.7 μg/mL). Although only small concentrations of gallic acid (8 μg/mg dried extract) were detected in the pomegranate fruit extract, microbial metabolism of punicalagin (276.2 μg/mg dried extract) in the rumen could result in the formation of substantial amounts of gallic acid, potentially contributing to significant toxicity.

Grasses accumulate large amounts of silicon (Si) which acts as a highly effective physical defence against insect herbivory, however recent evidence shows that Si supplementation also modifies plant secondary metabolite concetrations. Changes in plant secondary metabolites concentrations can have cascading effects on higher trophic levels, such as parasitoids, as they are dependent on the host herbivore for growth and development. However, relatively little is known about how Si application affects higher trophic levels. We examined the effects of Si addition on alkaloid content in leaves of Phalaris aquatica (Poaceae) and the effect on interactions between an aphid (Rhopalosiphum padi) and its parasitoid (Aphidius colemani). Si supplementation had no effect on aphid abundance or parasitism rate. Adult aphids, aphid mummies (parasitised aphids) and the emergent parasitoids were, however, significantly smaller on Si+ plants. Parasitoid traits (size and emergence) were correlated with aphid mummy size. Si addition reduced parasitoid emergence rate and size due to reduced host mummy size, in addition, significantly fewer females emerged from mummies on Si+ plants. Aphid infestation significantly altered alkaloids concentrations, reducing gramine by 80% while increasing tryptamine by 91% in Si- plants. Si addition reduced aphid-induced tryptamine concentrations by 64% and increased 5-MeO-tryptamine by over 800% in control and 142% in aphid infested plants. Our results show that while Si addition has modest impacts on the herbivore, it significantly alters secondary metabolites and has stronger effects on the higher trophic level through changes in the quality of the parasitised host.

Cheese microbiota and metabolites and their inter-relationships that underpin specific cheese quality attributes remain poorly understood. Here we report that multi-omics and integrative data analysis (multiple co-inertia analysis, MCIA) can be used to gain deeper insights into these relationships and identify microbiota and metabolite fingerprints that could be used to monitor product quality and authenticity. Our study into different brands of artisanal and industrial cheddar cheeses showed that Streptococcus, Lactococcus and Lactobacillus were the dominant taxa with overall microbial community structures differing not only between industrial and artisanal cheeses but also among different cheese brands. Metabolome analysis also revealed qualitative and semi-quantitative differences in metabolites between different cheeses. This also included the presence of two compounds (3-hydroxy propanoic acid and O-methoxycatechol-O-sulphate) in artisanal cheese that have not been previously reported in any type of cheese. Integrative analysis of multi-omics datasets revealed that highly similar cheeses, identical in age and appearance, could be distinctively clustered according to cheese type and brand. Furthermore, the analysis detected strong relationships, some previously unknown, which existed between the cheese microbiota and metabolome, and uncovered specific taxa and metabolites that contributed to these relationships. These results highlight the potential of this approach for identifying product specific microbe/metabolite signatures that could be used to monitor and control cheese quality and product authenticity.

The calcite tests of foraminifera lie in marine sediments for thousands to millions of years, before being analysed to generate trace element and isotope palaeoproxy records. These sediments constitute a distinct physio-chemical environment from the conditions in which the tests formed. Storage in sediments can modify the trace element and isotopic content of foraminiferal calcite through diagenetic alteration, which has the potential to confound their palaeoceanographic interpretation. A previous study of G. tumida from the Ontong Java Plateau, western equatorial Pacific, found that preferential dissolution of higher-Mg chamber calcite, and the preservation of a low-Mg crust on the tests significantly reduced whole-test Mg/Ca and Sr/Ca [Brown and Elderfield, 1996]. Here, we revisit these specimens with a combination of synchrotron X-ray computed tomography (sXCT) and electron probe micro-analyses (EPMA) to re-evaluate the nature of their diagenetic alteration. The dissolution of higher-Mg calcite with depth was directly observed in the sXCT data, confirming the inference of the previous study. The sXCT data further reveal a thickening of the chemically and structurally distinct calcite crust with depth. We propose that these crusts have a diagenetic origin, driven by the simultaneous dissolution of high-Mg chamber calcite and precipitation of low-Mg crust from the resulting modified pore-water solution. While the breadth of the study is limited by the nature of the techniques, the observation of both dissolution and re-precipitation of foraminiferal calcite serves to demonstrate the action of two simultaneous diagenetic alteration processes, with significant impacts on the resulting palaeoproxy signals.

This study employed a semi-quantitative, multiplexed tandem PCR (MT-PCR) to assess the prevalence and infection intensity of four genotypes (buffeli, chitose, ikeda and type 5) of Theileria orientalis in cattle in Australia. Genomic DNA samples from blood samples (n=448) collected from 27 to 32 dairy cows from each of 15 dairy herds with a history of recent theileriosis outbreaks (Group 1), and from blood samples available from 24 cows with or without oriental theileriosis (Group 2) were tested using MT-PCR. Results revealed that all four genotypes were present in Group 1 cattle; genotype buffeli had the highest prevalence (80.5%), followed by genotypes ikeda (71.4%), chitose (38.6%) and type 5 (20.3%). Genotype ikeda had the highest average infection intensity in the cattle (relating to 55,277 DNA copies), followed by buffeli, chitose and type 5 (6354-51,648 copies). For Group 2, results indicated that genotype ikeda had a significantly higher average intensity of infection than buffeli in symptomatic cattle (P

Phalaris aquatica is known to cause toxicity in livestock in the form of acute or chronic staggers or sudden death neurological (SDN) syndrome. Breeding of cultivars that produce lower concentrations of suspected alkaloid toxins has been conducted, but these cultivars continue to cause staggers and SDN toxicity. Field samples of grazed phalaris pasture were collected during one growth season (February–June 2016), and from pastures where cases of staggers and/or SDN had occurred in previous years, and immediately after two cases of toxicity. Pasture collected from a paddock where a case of SDN occurred 4 days prior had elevated levels of 5-methoxy-N,N-dimethyltryptamine (5-MeO DMT) and slightly elevated levels of dimethyltryptamine (DMT) compared with other collections from the region. Pasture collected from a paddock at the time of a case of phalaris staggers did not have elevated levels of the quantified alkaloids. Across the measurement period, potentially toxic alkaloids gramine, hordenine, DMT and 5-MeO DMT were observed to decrease in concentration, whereas β-carboline (norharmane) was not detected in any sample. Excessive drying out of dormant plants was hypothesised to be a risk factor for phalaris toxicity. Continued management of potentially toxic phalaris pasture could include measures to manipulate the physiological processes that result in increased toxic alkaloids, including methods to reduce drying out of dormant phalaris plants, and managing stocking rates and grazing species to mitigate potential toxicity.

The transcriptome is extensively and dynamically regulated by a network of RNA modifying factors. RNA editing enzymes APOBEC (apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like) and ADAR (adenosine deaminase, RNA-specific) irreversibly recode primary RNA sequences, whereas newly described methylases (writers) and de-methylases (erasers) dynamically alter RNA molecules in response to environmental conditions. RNA modifications can affect RNA splicing, nuclear-cytoplasmic transport, translation, and regulation of gene expression by RNA interference. In addition, tRNA base modifications, processing, and regulated cleavage have been shown to alter global patterns of mRNA translation in response to cellular stress pathways. Recent studies, some of which were discussed at this workshop, have rekindled interest in the emerging roles of RNA modifications in health and disease. On September 10th, 2014, the Division of Cancer Biology, NCI sponsored a workshop to explore the role of epitranscriptomic RNA modifications and tRNA processing in cancer progression. The workshop attendees spanned a scientific range including chemists, virologists, and RNA and cancer biologists. The goal of the workshop was to explore the interrelationships between RNA editing, epitranscriptomics, and RNA processing and the enzymatic pathways that regulate these activities in cancer initiation and progression. At the conclusion of the workshop, a general discussion focused on defining the major challenges and opportunities in this field, as well as identifying the tools, technologies, resources and community efforts required to accelerate research in this emerging area.

In a set of independent student focus groups conducted at Leeds University by the Royal academy of engineering, a common concern regarding laboratory sessions was that an emphasis on assessment often meant that, due to time pressures, students concentrated on gathering data rather than understanding the underlying engineering principles. In 2008, with support from the Higher education academy engineering Subject Centre, the DaSh system was developed to allow students to upload and share data, in order to promote collaborative and deeper learning. Data could be uploaded in real-time, via the internet, allowing results to be made available immediately for comparison with their peers’, whilst still in the laboratory in front of the equipment. This facilitated learning in two distinct ways. at a basic level, students were able to rapidly spot and correct measurement or calculation errors. at a more advanced level, conclusions could be drawn from the observation of hundreds of data points (rather than just five or ten), something that would otherwise have been impossible, had they worked independently. Following its positive impact on the student learning experience, data sharing was incorporated into a ReLOaD (Real Labs Operated at Distance) session, allowing the experiment to be repeated anywhere with internet access. DaSh was evaluated by comparing performance on similar sessions run with and without data sharing, observing behaviour within the laboratory, completion of questionnaires after the sessions and from focus groups. Through these methods, results have shown that the system has worked well, has been popular with the students and has been beneficial to their learning.

This paper looks at potential issues that may be encountered by engineering departments in the delivery of their curriculum to a more diverse student base resulting from the success of widening participation (WP). This paper outlines a piloted solution to these issues by setting up weblabs: short interactive experiments that can be carried out by the students at any time from anywhere and shows how a system originally developed to allow remote access to real experimental equipment (ReLOAD) can also be used to support the learning needs of a diverse student base. ReLOAD was incorporated into two different courses at University College London (UCL) and The University of Leeds, each with high proportions of WP students; and the use of the tool and feedback from the students was recorded. What can be seen from this research is that, whilst supporting the general student population in a positive way, the tool can also be shown to give specific support for issues encountered by WP students.

A hybrid laser arc welding system incorporating a plasma arc in a triangulated configuration (plasma augmented laser welding – PALW) was used to produce bead on plate welds in 6 mm low carbon steel. Laser powers up to 5 kW and arc currents up to 150 A were investigated. Plasma augmented laser welding allowed an increase in full penetration welding speed of 100% or an increase in penetration of between 25 and 100%, compared with the laser alone. At speeds of 2 m min−1 and above, PALW and laser alone were found to be equal with respect to fusion zone area per kW (mm2 kW−1). Plasma augmented laser welding was equivalent in terms of welding energy utilisation (mm3 J−1 of fusion zone) at 2 m min−1 and superior above 2 m min−1. Full penetrating PALW allows significant energy losses via the keyhole root exit. Only when the keyhole root closes can the full benefits of the hybrid process be manifested in the workpiece.

Previous studies have indicated that human immunodeficiency virus type 1 (HIV-1) protease inhibitors (PIs) are less active at blocking viral replication in HIV-1 infected peripheral blood monocytes/macrophages (M/M) than in HIV-1-infected T cells. We explored the hypothesis that oxidative modification and/or metabolism of the PIs in M/M might account for this reduced potency. We first tested the susceptibility of several PIs (kynostatin-272 [KNI-272], saquinavir, indinavir, ritonavir, or JE-2147) to oxidation after exposure to hydrogen peroxide (H2O2): only KNI-272 was highly susceptible to oxidation. Treatment of KNI-272 with low millimolar concentrations of H2O2resulted in mono-oxidation of the sulfur in theS-methyl cysteine (methioalanine) moiety, as determined by reversed-phase high-performance liquid chromatography and mass spectrometry (RP-HPLC/MS). Higher concentrations of H2O2led to an additional oxidation of the sulfur in the thioproline moiety of KNI-272. None of the PIs were metabolized or oxidized when added to T cells and cultured for up to 12 days. However, when KNI-272 was added to M/M, the concentration of the original KNI-272 steadily decreased with a corresponding increase in the production of three KNI-272 metabolites as identified by RP-HPLC/MS. The structures of these metabolites were different from those produced by H2O2treatment. The two major products of M/M metabolism of KNI-272 were identified as isomeric forms of KNI-272 oxidized solely on the thioproline ring. Both metabolites had reduced capacities to inhibit HIV-1 protease activity when tested in a standard HIV-1 protease assay. These studies demonstrate that antiviral compounds can be susceptible to oxidative modification in M/M and that this can affect their antiviral potency.

The impetus for this multiphased project was the realization that rheumatoid arthritis (RA) is not only physically debilitating, but also a cause of severe psychological distress, which is often unacknowledged. A small sample of patients (n=15) were interviewed to identify their main areas of psychological distress caused by RA, and data were analysed thematically. These themes formed the basis of a questionnaire that was distributed to a random sample of inpatients and outpatients with RA. This larger sample (n=140) prioritized the areas of distress that were identified by the interviewed sample of patients. This led to the development of an education programme for nurses.The authors describe the impetus for the project, the activities and processes associated with data collection, and the development and evaluation of the education programme.