15,982 research outputs found

    Domains of invasion organelle proteins from apicomplexan parasites are homologous with the Apple domains of blood coagulation factor XI and plasma pre-kallikrein and are members of the PAN module superfamily

    Get PDF
    AbstractMicronemes are specialised organelles, found in all apicomplexan parasites, which secrete molecules that are essential for parasite attachment to and invasion of host cells. Regions of several microneme proteins have sequence similarity to the Apple domains (A-domains) of blood coagulation factor XI (FXI) and plasma pre-kallikrein (PK). We have used mass spectrometry on a recombinant-expressed, putative A-domain from the microneme protein EtMIC5 from Eimeria tenella, to demonstrate that three intramolecular disulphide bridges are formed. These bridges are analogous to those that stabilise A-domains in FXI and PK. The data confirm that the apicomplexan domains are structural homologues of A-domains and are therefore novel members of the PAN module superfamily, which also includes the N-terminal domains of members of the plasminogen/hepatocyte growth factor family. The role of A-domains/PAN modules in apicomplexan parasites is not known, but their presence in the microneme suggests that they may be important for mediating protein–protein or protein–carbohydrate interactions during parasite attachment and host cell invasion

    Addressing the needs of the children’s integrated workforce: A method for developing collaborative practice through joint learning

    Get PDF
    The delivery of welfare, health and educational provision to the majority of children aged 0–18 in England is primarily led by local authorities via their children’s integrated service. In 2004 the children’s integrated service model was launched and it promised the benefits of an integrated and collaborative system of working, regarding flexibility and responsiveness to national policy, local development and capacity building (Robinson et al, 2008). However, the implementation and emergence of this model has been characterised by competing local and national agendas, practitioner misunderstanding and lack of trust, a lack of strong leadership and also financial restrictions. It can therefore be contended that conceptually children’s integrated services are not operating fully with a collaborative and integrated workforce. As a possible solution to the current situation, it is proposed that joint learning, along with a combined continual professional development (CPD) framework, be made available as a valuable starting point for such organisations. Learning and working together has benefits for children and practitioners, and especially, as this article will argue, for playwork practitioners

    Two Decades of Imperial Failure: Theorizing U.S. Regime Change Efforts in Venezuela from Bush II to Trump

    Get PDF
    Former Venezuelan President Hugo Chávez ushered in the Pink Tide and the rise of the left in Latin America at the turn of the 21st century. Chávez initially won presidential elections in 1998 based on the promise of participatory democracy and tackling economic inequality, and thereafter by championing 21st Century Socialism. From the beginning, Chávez challenged U.S. global leadership by condemning its vision for the world and by cultivating an anti-imperial nexus of allies. This pattern has continued under current President Nicolás Maduro. In response, the U.S. has opposed the Venezuelan socialists throughout three successive presidential administrations: Bush II, Obama, and Trump. Taking influence from Michael Mann’s IEMP model of social power, we detail the ideological, economic, military, and political strategies these administrations have used to undermine the Venezuelan government and assist right-wing opposition parties and civil society groups in Venezuela. While Bush II and Obama primarily sought to depose Chávez by bolstering right-wing political parties and groups that aimed to unseat Chávez at the ballot box, Trump has recognized a parallel government open to an extra-legal change of government and openly called for coercive regime change through a military coup d’état

    Carrying capacity models should not use fixed prey density thresholds: a plea for using more tools of behavioural ecology

    Get PDF
    Earlier studies have developed models of carrying capacity to predict the number of animals a certain area can support. These models assume that resources are not renewed after consumption (‘standing stock’ models), and that the initial number of prey and the rate of prey consumption determine the time a population of foragers can live in an area. Within such areas, foragers give up feeding at a sub-site or patch when intake rates no longer cover energy expenditure. To improve the success rate of the models’ predictions, we here change the existing rate-maximising models into fitness-maximising models, and include dynamics in the availability of patches. These new (conceptual) models show that the approaches used so far may over- as well as underestimate carrying capacity. We review empirical studies that have aimed to estimate carrying capacity, and discuss how concepts have been confused. We make explicit suggestions on how to proceed in predicting carrying capacities in future studies.

    Barriers That Influence Adoption of ACL Injury Prevention Programs Among High School Girls’ Soccer Coaches

    Get PDF
    Click the PDF icon to download the abstract

    Experiences of Establishing an Academic Early Phase Clinical Trials Unit

    Get PDF
    Background: Early phase trials are essential in drug development, determining appropriate dose levels and assessing preliminary activity. These trials are undertaken by industry and academia, with increasing collaborations between the two. There is pressure to perform these trials quickly, safely and robustly. However, there are inherent differences between developing and managing early phase, compared to late phase, drug trials. This paper describes an approach to establishing an academically-led early phase trial portfolio, highlighting lessons learned and sharing experiences. Methods: In 2009 the University of Leeds Clinical Trials Research Unit became the Clinical Trials Coordinating Office for Myeloma UK’s phase I and II trials. We embarked on a transition from working extensively in phase III to early phase trials development and conduct. This involved evaluating and revising our well-established standard operating procedures, visiting other academic early phase units, and developing essential new documentation and processes. Results: A core team of trial and data managers and statisticians was established to facilitate expertise and knowledge retention. A detailed training plan was implemented focusing on essential standard practices for early phase. These included pharmacovigilance, recruitment, trial design and set-up, data and site monitoring, and oversight committees. Training in statistical methods for early phase trials was incorporated. Conclusion: Initial scoping of early phase trial management and conduct was essential in establishing this early phase portfolio. Many of the processes developed were successful. However, regular review and evaluation were implemented to enable changes and ensure efficiencies. It is recommended that others embarking on this venture build on the experiences described in this article
    • …
    corecore