62 research outputs found

    Creating Control Amidst the Chaos: Collaborating on a Controlled Vocabulary During COVID

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    While having a controlled vocabulary for our IR was an aspiration, with limited staffing and ad hoc additions, it was not a priority. Some items were added with keywords, most often supplied by faculty focused solely on their subject area, and others had no keywords. It seemed with every addition, the idea of implementing—and more importantly editing earlier submissions—slipped further away. However, when the shift to remote work meant that staff needed projects, many items on the IR wish list became a reality, including the controlled vocabulary. During this session, we will walk you through the process of how we assessed what we had, implemented order, and made a plan of how to maintain (and expand) the controlled vocabulary going forward. You will hear about what worked, what did not, and how we turned our 2020 lemons into some pretty sweet IR lemonade

    An alternative strategy for trypanosome survival in the mammalian bloodstream revealed through genome and transcriptome analysis of the ubiquitous bovine parasite Trypanosoma (Megatrypanum) theileri

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    There are hundreds of Trypanosoma species that live in the blood and tissue spaces of their vertebrate hosts. The vast majority of these do not have the ornate system of antigenic variation that has evolved in the small number of African trypanosome species, but can still maintain long term infections in the face of the vertebrate adaptive immune system. Trypanosoma theileri is a typical example, it has a restricted host range of cattle and other Bovinae and is only occasionally reported to cause patent disease although no systematic survey of the effect of infection on agricultural productivity has been performed. Here, a detailed genome sequence and a transcriptome analysis of gene expression in bloodstream form T. theileri have been performed. Analysis of the genome sequence and expression showed that T. theileri has a typical kinetoplastid genome structure and allowed a prediction that it is capable of meiotic exchange, gene silencing via RNA interference and, potentially, density-dependent growth control. In particular, the transcriptome analysis has allowed a comparison of two distinct trypanosome cell surfaces, T. brucei and T. theileri, that have each evolved to enable the maintenance of a long-term extracellular infection in cattle. The T. theileri cell surface can be modelled to contain a mixture of proteins encoded by four novel large and divergent gene families and by members of a major surface protease gene family. This surface composition is distinct from the uniform variant surface glycoprotein coat on African trypanosomes providing an insight into a second mechanism used by trypanosome species that proliferate in an extracellular milieu in vertebrate hosts to avoid the adaptive immune response

    Structure of the trypanosome transferrin receptor reveals mechanisms of ligand recognition and immune evasion.

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    To maintain prolonged infection of mammals, African trypanosomes have evolved remarkable surface coats and a system of antigenic variation1. Within these coats are receptors for macromolecular nutrients such as transferrin2,3. These must be accessible to their ligands but must not confer susceptibility to immunoglobulin-mediated attack. Trypanosomes have a wide host range and their receptors must also bind ligands from diverse species. To understand how these requirements are achieved, in the context of transferrin uptake, we determined the structure of a Trypanosoma brucei transferrin receptor in complex with human transferrin, showing how this heterodimeric receptor presents a large asymmetric ligand-binding platform. The trypanosome genome contains a family of around 14 transferrin receptors4, which has been proposed to allow binding to transferrin from different mammalian hosts5,6. However, we find that a single receptor can bind transferrin from a broad range of mammals, indicating that receptor variation is unlikely to be necessary for promiscuity of host infection. In contrast, polymorphic sites and N-linked glycans are preferentially found in exposed positions on the receptor surface, not contacting transferrin, suggesting that transferrin receptor diversification is driven by a need for antigenic variation in the receptor to prolong survival in a host

    The Brief Solastalgia Scale: A Psychometric Evaluation and Revision

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    Witnessing degradation and loss to one’s home environment can cause the negative emotional experience of solastalgia. We review the psychometric properties of the 9-item Solastalgia subscale from the Environmental Distress Scale (Higginbotham et al. (EcoHealth 3:245–254, 2006)). Using data collected from three large, independent, adult samples (N = 4229), who were surveyed soon after the 2019/20 Australian bushfires, factor analyses confirmed the scale’s unidimensionality, while analyses derived from Item Response Theory highlighted the poor psychometric performance and redundant content of specific items. Consequently, we recommend a short-form scale consisting of five items. This Brief Solastalgia Scale (BSS) yielded excellent model fit and internal consistency in both the initial and cross-validation samples. The BSS and its parent version provide very similar patterns of associations with demographic, health, life satisfaction, climate emotion, and nature connectedness variables. Finally, multi-group confirmatory factor analysis demonstrated comparable construct architecture (i.e. configural, metric, and scalar invariance) across validation samples, gender categories, and age. As individuals and communities increasingly confront and cope with climate change and its consequences, understanding related emotional impacts is crucial. The BSS promises to aid researchers, decision makers, and practitioners to understand and support those affected by negative environmental change

    Mental health, wellbeing and resilience after the 2019-20 bushfires: The Australian national bushfire health and wellbeing survey - A preliminary report

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    This report provides an overview of the mental health and wellbeing following Australia’s 2019-20 bushfires, with data recorded 12-18 months after the bushfire season ended. Findings are based on 3,083 adults' responses in an online survey to standard measures of psychological distress (i.e., symptoms of depression, anxiety, stress and posttraumatic stress disorder), loneliness, social connectedness, financial security and psychological resilience (i.e., resilient coping, posttraumatic growth and psychological wellbeing). A novel framework for classifying respondents' severity of bushfire exposure is used based on respondents' range of experiences, rather than their postal code alone. High rates of depression, anxiety and stress were recorded across the whole sample, with severity of bushfire exposure associated with greater severity of distress. For men and women with high bushfire exposure, one in five reported symptoms associated with the clinical cut-off for PTSD. Parents with dependents impacted by bushfire reported more behavioural and emotional challenges in their children than children in communities not impacted by bushfire. Psychological distress among Aboriginal and Torres Strait Islander peoples was especially high among women affected by bushfire, compared to Indigenous men and non-Indigenous people. Markers of psychological resilience across the whole sample included endorsement of resilient coping, personal growth and psychological wellbeing. Notably, bushfire-affected, Indigenous, and parent respondents all reported higher levels of wellbeing and growth. Six key recommendations are put forward to meet the ongoing mental health and wellbeing needs of people affected by bushfire.This research was supported by the Australian Government’s Medical Research Future Fund (MRFF), National Health and Medical Research Council (NHMRC), Stream 2: Mental health impacts of bushfires on affected communities (Grant ID: APP1201732)

    A single dose of antibody-drug conjugate cures a stage 1 model of African trypanosomiasis.

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    Infections of humans and livestock with African trypanosomes are treated with drugs introduced decades ago that are not always fully effective and often have severe side effects. Here, the trypanosome haptoglobin-haemoglobin receptor (HpHbR) has been exploited as a route of uptake for an antibody-drug conjugate (ADC) that is completely effective against Trypanosoma brucei in the standard mouse model of infection. Recombinant human anti-HpHbR monoclonal antibodies were isolated and shown to be internalised in a receptor-dependent manner. Antibodies were conjugated to a pyrrolobenzodiazepine (PBD) toxin and killed T. brucei in vitro at picomolar concentrations. A single therapeutic dose (0.25 mg/kg) of a HpHbR antibody-PBD conjugate completely cured a T. brucei mouse infection within 2 days with no re-emergence of infection over a subsequent time course of 77 days. These experiments provide a demonstration of how ADCs can be exploited to treat protozoal diseases that desperately require new therapeutics

    Mainstreaming forecast based action into national disaster risk management systems: experience from drought risk management in Kenya

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    Drought and food security crises heighten risks to lives and livelihoods in East Africa. In recent years, a shift towards acting in advance of such events has gained momentum, notably among the humanitarian and development community. This shift is premised on tools that link climate forecasts with pre-agreed actions and funding, known as Forecast-based Action (FbA), or anticipatory action more widely. While FbA approaches have been developed by a number of humanitarian agencies, the key to scaling-up is mainstreaming these approaches into national risk management systems. This paper addresses this gap in the context of drought risk management in Kenya. We analyse Kenya's current drought management system to assess the potential usability of climate forecast information within the existing system, and outline steps towards improved usability of climate information. Further, we note the critical importance of enabling institutions and reliable financing to ensure that information can be consistently used to trigger early action. We discuss the implications of this for scaling-up FbA into national risk management systems

    Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

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    Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

    A receptor for the complement regulator factor H increases transmission of trypanosomes to tsetse flies

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    Abstract: Persistent pathogens have evolved to avoid elimination by the mammalian immune system including mechanisms to evade complement. Infections with African trypanosomes can persist for years and cause human and animal disease throughout sub-Saharan Africa. It is not known how trypanosomes limit the action of the alternative complement pathway. Here we identify an African trypanosome receptor for mammalian factor H, a negative regulator of the alternative pathway. Structural studies show how the receptor binds ligand, leaving inhibitory domains of factor H free to inactivate complement C3b deposited on the trypanosome surface. Receptor expression is highest in developmental stages transmitted to the tsetse fly vector and those exposed to blood meals in the tsetse gut. Receptor gene deletion reduced tsetse infection, identifying this receptor as a virulence factor for transmission. This demonstrates how a pathogen evolved a molecular mechanism to increase transmission to an insect vector by exploitation of a mammalian complement regulator
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