Mercury trends in colonial waterbird eggs downstream of the oil sands region of Alberta, Canada.

Mercury levels were measured in colonial waterbird eggs collected from two sites in northern Alberta and one site in southern Alberta, Canada. Northern sites in the Peace-Athabasca Delta and Lake Athabasca were located in receiving waters of the Athabasca River which drains the oil sands industrial region north of Fort McMurray, Alberta. Temporal trends in egg mercury (Hg) levels were assessed as were egg stable nitrogen isotope values as an indicator of dietary change. In northern Alberta, California and Ring-billed Gulls exhibited statistically significant increases in egg Hg concentrations in 2012 compared to data from the earliest year of sampling. Hg levels in Caspian and Common Tern eggs showed a nonstatistically significant increase. In southern Alberta, Hg concentrations in California Gull eggs declined significantly through time. Bird dietary change was not responsible for any of these trends. Neither were egg Hg trends related to recent forest fires. Differences in egg Hg temporal trends between northern and southern Alberta combined with greater Hg levels in eggs from northern Alberta identified the likely importance of local Hg sources in regulating regional Hg trends. Hg concentrations in gull and Common Tern eggs were generally below generic thresholds associated with toxic effects in birds. However, in 2012, Hg levels in the majority of Caspian Tern eggs exceeded the lower toxicity threshold. Increasing Hg levels in eggs of multiple species nesting downstream of the oil sands region of northern Alberta warrant continued monitoring and research to further evaluate Hg trends and to conclusively identify sources.

Learning From Student Experience: Development of an International Multimodal Patient Safety Education Package.

BACKGROUND: Patient safety is a global concern. Learning to provide safe, high-quality care is core to nursing education. PROBLEM: Students are exposed to diverse clinical practices, and experiences may vary between placements and across countries. Student experience is seldom used as an educational resource. APPROACH: An international, European Union-funded project, Sharing Learning from Practice for Patient Safety (SLIPPs), aimed to develop an innovative online educational package to assist patient safety learning. Based on student reported data and educational theory, multiple elements were iteratively developed by a multicountry, multidisciplinary group. OUTCOMES: The educational package is freely available on the SLIPPs Web site. Materials include a student reporting and reflection tool, virtual seminars, student reports data set, pedagogical game, high-fidelity simulation scenarios, scenario development and use guidelines, debriefing session model, and videos of simulations already performed. CONCLUSIONS: E-learning enables removal of physical barriers, allowing educators, professionals, and students from all over the world to collaborate, interact, and learn from each other.

Development of an International Tool for Students to Record and Reflect on Patient Safety Learning Experiences.

BACKGROUND: Underpinning all nursing education is the development of safe practitioners who provide quality care. Learning in practice settings is important, but student experiences vary. PURPOSE: This study aimed to systematically develop a robust multilingual, multiprofessional data collection tool, which prompts students to describe and reflect on patient safety experiences. APPROACH: Core to a 3-year, 5-country, European project was development of the SLIPPS (Sharing Learning from Practice for Patient Safety) Learning Event Recording Tool (SLERT). Tool construction drew on literature, theory, multinational and multidisciplinary experience, and involved pretesting and translation. Piloting included assessing usability and an initial exploration of impact via student interviews. OUTCOMES: The final SLERT (provided for readers) is freely available in 5 languages and has face validity for nursing across 5 countries. Student reports (n = 368) were collected using the tool. CONCLUSIONS: The tool functions well in assisting student learning and for collecting data. Interviews indicated the tool promoted individual learning and has potential for wider clinical teams.

Manipulating glucocorticoids in wild animals: basic and applied perspectives.

One of the most comprehensively studied responses to stressors in vertebrates is the endogenous production and regulation of glucocorticoids (GCs). Extensive laboratory research using experimental elevation of GCs in model species is instrumental in learning about stressor-induced physiological and behavioural mechanisms; however, such studies fail to inform our understanding of ecological and evolutionary processes in the wild. We reviewed emerging research that has used GC manipulations in wild vertebrates to assess GC-mediated effects on survival, physiology, behaviour, reproduction and offspring quality. Within and across taxa, exogenous manipulation of GCs increased, decreased or had no effect on traits examined in the reviewed studies. The notable diversity in responses to GC manipulation could be associated with variation in experimental methods, inherent differences among species, morphs, sexes and age classes, and the ecological conditions in which responses were measured. In their current form, results from experimental studies may be applied to animal conservation on a case-by-case basis in contexts such as threshold-based management. We discuss ways to integrate mechanistic explanations for changes in animal abundance in altered environments with functional applications that inform conservation practitioners of which species and traits may be most responsive to environmental change or human disturbance. Experimental GC manipulation holds promise for determining mechanisms underlying fitness impairment and population declines. Future work in this area should examine multiple life-history traits, with consideration of individual variation and, most importantly, validation of GC manipulations within naturally occurring and physiologically relevant ranges.

Binding between Crossveinless-2 and Chordin von Willebrand factor type C domains promotes BMP signaling by blocking Chordin activity.

BACKGROUND: Crossveinless-2 (CV2) is an extracellular BMP modulator protein of the Chordin family, which can either enhance or inhibit BMP activity. CV2 binds to BMP2 via subdomain 1 of the first of its five N-terminal von Willebrand factor type C domains (VWC1). Previous studies showed that this BMP binding is required for the anti-, but not for the pro-BMP effect of CV2. More recently, it was shown that CV2 can also bind to the BMP inhibitor Chordin. However, it remained unclear which domains mediate this binding, and whether it accounts for an anti- or pro-BMP effect. PRINCIPAL FINDINGS: Here we report that a composite interface of CV2 consisting of subdomain 2 of VWC1 and of VWC2-4, which are dispensable for BMP binding, binds to the VWC2 domain of Chordin. Functional data obtained in zebrafish embryos indicate that this binding of Chordin is required for CV2's pro-BMP effect, which actually is an anti-Chordin effect and, at least to a large extent, independent of Tolloid-mediated Chordin degradation. We further demonstrate that CV2 mutant versions that per se are incapable of BMP binding can attenuate the Chordin/BMP interaction. CONCLUSIONS: We have physically dissected the anti- and pro-BMP effects of CV2. Its anti-BMP effect is obtained by binding to BMP via subdomain1 of the VWC1 domain, a binding that occurs in competition with Chordin. In contrast, its pro-BMP effect is achieved by direct binding to Chordin via subdomain 2 of VWC1 and VWC2-4. This binding seems to induce conformational changes within the Chordin protein that weaken Chordin's affinity to BMP. We propose that in ternary Chordin-CV2-BMP complexes, both BMP and Chordin are directly associated with CV2, whereas Chordin is pushed away from BMP, ensuring that BMPs can be more easily delivered to their receptors.

Control of Dpp morphogen signalling by a secreted feedback regulator.

In many instances during development, morphogens specify cell fates by forming concentration gradients. In the Drosophila melanogaster wing imaginal disc, Decapentaplegic (Dpp), a bone morphogenetic protein (BMP), functions as a long-range morphogen to control patterning and growth. Dpp is secreted from a stripe of cells at the anterior-posterior compartment boundary and spreads into both compartments to generate a characteristic BMP activity gradient. Ever since the identification of the morphogen activity of Dpp in the developing wing, the system has served as a paradigm to understand how long-range gradients are established and how cells respond to such gradients. Here we reveal the tight and direct connection of these two processes with the identification and characterization of pentagone (pent), a transcriptional target of BMP signalling encoding a secreted regulator of the pathway. Absence of pent in the wing disc causes a severe contraction of the BMP activity gradient resulting in patterning and growth defects. We show that Pent interacts with the glypican Dally to control Dpp distribution and provide evidence that proper establishment of the BMP morphogen gradient requires the inbuilt feedback loop embodied by Pent.

Crystal structure analysis reveals how the Chordin family member crossveinless 2 blocks BMP-2 receptor binding.

Crossveinless 2 (CV-2) is an extracellular BMP modulator protein belonging to the Chordin family. During development it is expressed at sites of high BMP signaling and like Chordin CV-2 can either enhance or inhibit BMP activity. CV-2 binds to BMP-2 via its N-terminal Von Willebrand factor type C (VWC) domain 1. Here we report the structure of the complex between CV-2 VWC1 and BMP-2. The tripartite VWC1 binds BMP-2 only through a short N-terminal segment, called clip, and subdomain (SD) 1. Mutational analysis establishes that the clip segment and SD1 together create high-affinity BMP-2 binding. All four receptor-binding sites of BMP-2 are blocked in the complex, demonstrating that VWC1 acts as competitive inhibitor for all receptor types. In vivo experiments reveal that the BMP-enhancing (pro-BMP) activity of CV-2 is independent of BMP-2 binding by VWC1, showing that pro- and anti-BMP activities are structurally separated in CV-2.

The transcription factors Scl and Lmo2 act together during development of the hemangioblast in zebrafish.

The transcription factors Scl and Lmo2 are crucial for development of all blood. An important early requirement for Scl in endothelial development has also been revealed recently in zebrafish embryos, supporting previous findings in scl(-/-) embryoid bodies. Scl depletion culminates most notably in failure of dorsal aorta formation, potentially revealing a role in the formation of hemogenic endothelium. We now present evidence that the requirements for Lmo2 in zebrafish embryos are essentially the same as for Scl. The expression of important hematopoietic regulators is lost, reduced, or delayed, panendothelial gene expression is down-regulated, and aorta-specific marker expression is lost. The close similarity of the phenotypes for Scl and Lmo2 suggest that they perform these early functions in hemangioblast development within a multiprotein complex, as shown for erythropoiesis. Consistent with this, we find that scl morphants cannot be rescued by a non-Lmo2-binding form of Scl but can be rescued by non-DNA-binding forms, suggesting tethering to target genes through DNA-binding partners linked via Lmo2. Interestingly, unlike other hematopoietic regulators, the Scl/Lmo2 complex does not appear to autoregulate, as neither gene's expression is affected by depletion of the other. Thus, expression of these critical regulators is dependent on continued expression of upstream regulators, which may include cell-extrinsic signals.

Scl is required for dorsal aorta as well as blood formation in zebrafish embryos.

Blood and endothelial cells arise in close association in developing embryos, possibly from a shared precursor, the hemangioblast, or as hemogenic endothelium. The transcription factor, Scl/Tal1 (stem cell leukemia protein), is essential for hematopoiesis but thought to be required only for remodeling of endothelium in mouse embryos. By contrast, it has been implicated in hemangioblast formation in embryoid bodies. To resolve the role of scl in endothelial development, we knocked down its synthesis in zebrafish embryos where early precursors and later phenotypes can be more easily monitored. With respect to blood, the zebrafish morphants phenocopied the mouse knockout and positioned scl in the genetic hierarchy. Importantly, endothelial development was also clearly disrupted. Dorsal aorta formation was substantially compromised and gene expression in the posterior cardinal vein was abnormal. We conclude that scl is especially critical for the development of arteries where adult hematopoietic stem cells emerge, implicating scl in the formation of hemogenic endothelium.