Parasitoids of Leptoglossus occidentalis Heidemann (Heteroptera: Coreidae) in British Columbia

Eggs of the western conifer seed bug, Leptoglossus occidentalis Heidemann, were parasitized in the field in British Columbia, Canada, by Gryon pennsylvanicum (Ashmead), Anastatus pearsalli Ashmead and an unidentified Ooencyrtus spp. Ashmead. Leptoglossus occidentalis represents a new host record for all three parasitoids. Gryon pennsylvanicum has not previously been reported in Canada

Water resources data, models and decisions: International expert opinion on knowledge management for an uncertain but resilient future

© 2019 The Authors. Assessing the resilience of water resources systems requires knowledge of properties and performance, which depends on data availability and use within models and decision making. Connections between data, models and decision making are crucial to plan for uncertainty and invest in interventions. To explore international perceptions of these connections, we conducted a threeround Delphi survey with an expert panel (see Supplementary material, available with the online version of this paper). Consensus and divergence existed within and between countries on ability to manage data, modelling and decision making, with the most consensus seen on use of hydrometric databases. There was a wide range of models and tools utilised by participants and a shift occurred between first and second rounds to a preference for trying new modelling. There was consensus between and within all countries that every data type was important. River flow data consistently scored highest. Access to data and models primarily impacted evaluating future capacity, planning under uncertainty, policy implementation and conflict resolution. The panel called for reviewing existing and developing new policy, collaborative research and available funding all focusing on water resources data-model-decision integration. Findings offer a strategic view on knowledge management regarding connections between data, models and decision making through identification of consensus areas for future focus and dissensus areas for reprioritisation

Leading an Interprofessional Geriatric Clinical Skills Fair: A Train the Trainer Seminar

Objectives • Practice teaching skills related to interprofessional education (IPE) and geriatric competencies • Formulate an Action Plan and prepare to introduce an Interprofessional Geriatric Clinical Skills Fair at their own institutions • Recognize essential elements of a measurement tool that evaluates the effectiveness of an Interprofessional Geriatric Clinical Skills Fai

Glucosyltransferase-dependent and independent effects of Clostridioides difficile toxins during infection

Clostridioides difficile infection (CDI) is the leading cause of nosocomial diarrhea and pseudomembranous colitis in the USA. In addition to these symptoms, patients with CDI can develop severe inflammation and tissue damage, resulting in life-threatening toxic megacolon. CDI is mediated by two large homologous protein toxins, TcdA and TcdB, that bind and hijack receptors to enter host cells where they use glucosyltransferase (GT) enzymes to inactivate Rho family GTPases. GT-dependent intoxication elicits cytopathic changes, cytokine production, and apoptosis. At higher concentrations TcdB induces GT-independent necrosis in cells and tissue by stimulating production of reactive oxygen species via recruitment of the NADPH oxidase complex. Although GT-independent necrosis has been observed in vitro, the relevance of this mechanism during CDI has remained an outstanding question in the field. In this study we generated novel C. difficile toxin mutants in the hypervirulent BI/NAP1/PCR-ribotype 027 R20291 strain to test the hypothesis that GT-independent epithelial damage occurs during CDI. Using the mouse model of CDI, we observed that epithelial damage occurs through a GT-independent process that does not involve immune cell influx. The GT-activity of either toxin was sufficient to cause severe edema and inflammation, yet GT activity of both toxins was necessary to produce severe watery diarrhea. These results demonstrate that both TcdA and TcdB contribute to disease pathogenesis when present. Further, while inactivating GT activity of C. difficile toxins may suppress diarrhea and deleterious GT-dependent immune responses, the potential of severe GT-independent epithelial damage merits consideration when developing toxin-based therapeutics against CDI

Evaluation of an Interprofessional Geriatric Clinical Skills Fair

Objectives •Describe the utilization of an interprofessional geriatric clinical skills fair to impart knowledge and skills pertaining to both core geriatric and IPE competencies. •Prepare to introduce an Interprofessional Geriatric Clinical Skills Fair at one’s own institution •Recognize essential elements of a measurement tool that evaluates the effectiveness of an Interprofessional Geriatric Clinical Skills Fai

The Public Playground Paradox: "Child’s Joy" or Heterotopia of Fear?

Literature depicts children of the Global North withdrawing from public space to“acceptable islands”. Driven by fears both of and for children, the publicplayground – one such island – provides clear-cut distinctions between childhoodand adulthood. Extending this argument, this paper takes the original approach oftheoretically framing the playground as a heterotopia of deviance, examining –for the first time – three Greek public playground sites in relation to adjacentpublic space. Drawing on an ethnographic study in Athens, findings show fear tounderpin surveillance, control and playground boundary porosity. Normativeclassification as “children’s space” discourages adult engagement. However, in anovel and significant finding, a paradoxical phenomenon sees the playground’spresence simultaneously legitimizing playful behaviour in adjacent public spacefor children and adults. Extended playground play creates alternate orderings andnegotiates norms and hierarchies, suggesting significant wider potential toreconceptualise playground-urban design for an intergenerational public realm

BRAF/MAPK and GSK3 signaling converge to control MITF nuclear export

The close integration of the MAPK, PI3K, and WNT signaling pathways underpins much of development and is deregulated in cancer. In principle, combinatorial posttranslational modification of key lineage-specific transcription factors would be an effective means to integrate critical signaling events. Understanding how this might be achieved is central to deciphering the impact of microenvironmental cues in development and disease. The microphthalmia-associated transcription factor MITF plays a crucial role in the development of melanocytes, the retinal pigment epithelium, osteoclasts, and mast cells and acts as a lineage survival oncogene in melanoma. MITF coordinates survival, differentiation, cell-cycle progression, cell migration, metabolism, and lysosome biogenesis. However, how the activity of this key transcription factor is controlled remains poorly understood. Here, we show that GSK3, downstream from both the PI3K and Wnt pathways, and BRAF/MAPK signaling converges to control MITF nuclear export. Phosphorylation of the melanocyte MITF-M isoform in response to BRAF/MAPK signaling primes for phosphorylation by GSK3, a kinase inhibited by both PI3K and Wnt signaling. Dual phosphorylation, but not monophosphorylation, then promotes MITF nuclear export by activating a previously unrecognized hydrophobic export signal. Nonmelanocyte MITF isoforms exhibit poor regulation by MAPK signaling, but instead their export is controlled by mTOR. We uncover here an unanticipated mode of MITF regulation that integrates the output of key developmental and cancer-associated signaling pathways to gate MITF flux through the import–export cycle. The results have significant implications for our understanding of melanoma progression and stem cell renewal

Enhanced tonic GABAA inhibition in typical absence epilepsy

The cellular mechanisms underlying typical absence seizures, which characterize various idiopathic generalized epilepsies, are not fully understood, but impaired GABAergic inhibition remains an attractive hypothesis. In contrast, we show here that extrasynaptic GABAA receptor–dependent ‘tonic’ inhibition is increased in thalamocortical neurons from diverse genetic and pharmacological models of absence seizures. Increased tonic inhibition is due to compromised GABA uptake by the GABA transporter GAT–1 in the genetic models tested, and GAT–1 is critical in governing seizure genesis. Extrasynaptic GABAA receptors are a requirement for seizures in two of the best characterized models of absence epilepsy, and the selective activation of thalamic extrasynaptic GABAA receptors is sufficient to elicit both electrographic and behavioural correlates of seizures in normal animals. These results identify an apparently common cellular pathology in typical absence seizures that may have epileptogenic significance, and highlight novel therapeutic targets for the treatment of absence epilepsy.peer-reviewe