1,032 research outputs found

    The Drosophila caspase Ice is important for many apoptotic cell deaths and for spermatid individualization, a nonapoptotic process

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    Caspase family proteases play important roles in the regulation of apoptotic cell death. Initiator caspases are activated in response to death stimuli, and they transduce and amplify these signals by cleaving and thereby activating effector caspases. In Drosophila, the initiator caspase Nc (previously Dronc) cleaves and activates two short-prodomain caspases, Dcp-1 and Ice (previously Drice), suggesting these as candidate effectors of Nc killing activity. dcp-1-null mutants are healthy and possess few defects in normally occurring cell death. To explore roles for Ice in cell death, we generated and characterized an Ice null mutant. Animals lacking Ice show a number of defects in cell death, including those that occur during embryonic development, as well as during formation of adult eyes, arista and wings. Ice mutants exhibit subtle defects in the destruction of larval tissues, and do not prevent destruction of salivary glands during metamorphosis. Cells from Ice animals are also markedly resistant to several stresses, including X-irradiation and inhibition of protein synthesis. Mutations in Ice also suppress cell death that is induced by expression of Rpr, Wrinkled (previously Hid) and Grim. These observations demonstrate that Ice plays an important non-redundant role as a cell death effector. Finally, we demonstrate that Ice participates in, but is not absolutely required for, the non-apoptotic process of spermatid differentiation

    Defining Ecological Drought for the Twenty-First Century

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    THE RISING RISK OF DROUGHT. Droughts of the twenty-first century are characterized by hotter temperatures, longer duration, and greater spatial extent, and are increasingly exacerbated by human demands for water. This situation increases the vulnerability of ecosystems to drought, including a rise in drought-driven tree mortality globally (Allen et al. 2015) and anticipated ecosystem transformations from one state to another—for example, forest to a shrubland (Jiang et al. 2013). When a drought drives changes within ecosystems, there can be a ripple effect through human communities that depend on those ecosystems for critical goods and services (Millar and Stephenson 2015). For example, the “Millennium Drought” (2002–10) in Australia caused unanticipated losses to key services provided by hydrological ecosystems in the Murray–Darling basin—including air quality regulation, waste treatment, erosion prevention, and recreation. The costs of these losses exceeded AUD $800 million, as resources were spent to replace these services and adapt to new drought-impacted ecosystems (Banerjee et al. 2013). Despite the high costs to both nature and people, current drought research, management, and policy perspectives often fail to evaluate how drought affects ecosystems and the “natural capital” they provide to human communities. Integrating these human and natural dimensions of drought is an essential step toward addressing the rising risk of drought in the twenty-first century

    Cryo-EM structure of the active, Gs-protein complexed, human CGRP receptor

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    Calcitonin gene-related peptide (CGRP) is a widely expressed neuropeptide that plays a major role in sensory neurotransmission. The CGRP receptor is a heterodimer of the calcitonin receptor-like receptor (CLR) class B G-protein-coupled receptor and the type 1 transmembrane domain protein, receptor activity modifying protein (RAMP) 1. Herein, we report the 3.3 Ă… structure of the human CGRP receptor in complex with CGRP and the Gs40 protein heterotrimer determined by Volta phase plate cryo-electron microscopy. The RAMP transmembrane domain sits at the interface between transmembrane domains 3, 4 and 5 of CLR, and stabilises CLR extracellular loop 2. RAMP1 makes only limited direct interaction with CGRP, consistent with allosteric modulation of CLR as its key function. Molecular dynamics simulations indicate that RAMP1 provides stability to the receptor complex, particularly the location of the CLR extracellular domain. The work provides novel insight into the control of G-protein-coupled receptor function

    Rationale, design and methods for a randomised and controlled trial of the impact of virtual reality games on motor competence, physical activity, and mental health in children with developmental coordination disorder.

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    This is the final version of the article. Available from BioMed Central via the DOI in this record.BACKGROUND: A healthy start to life requires adequate motor development and physical activity participation. Currently 5-15% of children have impaired motor development without any obvious disorder. These children are at greater risk of obesity, musculoskeletal disorders, low social confidence and poor mental health. Traditional electronic game use may impact on motor development and physical activity creating a vicious cycle. However new virtual reality (VR) game interfaces may provide motor experiences that enhance motor development and lead to an increase in motor coordination and better physical activity and mental health outcomes. VR games are beginning to be used for rehabilitation, however there is no reported trial of the impact of these games on motor coordination in children with developmental coordination disorder. METHODS: This cross-over randomised and controlled trial will examine whether motor coordination is enhanced by access to active electronic games and whether daily activity, attitudes to physical activity and mental health are also enhanced. Thirty children aged 10-12 years with poor motor coordination (≤ 15th percentile) will be recruited and randomised to a balanced ordering of 'no active electronic games' and 'active electronic games'. Each child will participate in both conditions for 16 weeks, and be assessed prior to participation and at the end of each condition. The primary outcome is motor coordination, assessed by kinematic and kinetic motion analysis laboratory measures. Physical activity and sedentary behaviour will be assessed by accelerometry, coordination in daily life by parent report questionnaire and attitudes to physical activity, self-confidence, anxiety and depressed mood will be assessed by self report questionnaire. A sample of 30 will provide a power of > 0.9 for detecting a 5 point difference in motor coordination on the MABC-2 TIS scale (mean 17, sd = 5). DISCUSSION: This is the first trial to examine the impact of new virtual reality games on motor coordination in children with developmental coordination disorder. The findings will provide critical information to understand whether these electronic games can be used to have a positive impact on the physical and mental health of these children. Given the importance of adequate motor coordination, physical activity and mental health in childhood, this project can inform interventions which could have a profound impact on the long term health of this group of children. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12611000400965.This randomised and controlled trial is funded by the National Health and Medical Research Council (NHMRC) of Australia through project grant #533526. Professor Leon Straker and Doctor Anne Smith are supported by fellowships awarded from the NHMRC. No funding or other input to the study has been received from any electronic game design, manufacture or supply company

    Young pregnant women's views on the acceptability of screening for chlamydia as part of routine antenatal care

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    <p>Abstract</p> <p>Background</p> <p>In pregnancy, untreated chlamydia infection has been associated with adverse outcomes for both mother and infant. Like most women, pregnant women infected with chlamydia do not report genital symptoms, and are therefore unlikely to be aware of their infection. The aim of this study was to determine the acceptability of screening pregnant women aged 16-25 years for chlamydia as part of routine antenatal care.</p> <p>Methods</p> <p>As part of a larger prospective, cross-sectional study of pregnant women aged 16-25 years attending antenatal services across Melbourne, Australia, 100 women were invited to participate in a face-to-face, semi structured interview on the acceptability of screening for chlamydia during pregnancy. Women infected with chlamydia were oversampled (n = 31).</p> <p>Results</p> <p>Women had low levels of awareness of chlamydia before the test, retained relatively little knowledge after the test and commonly had misconceptions around chlamydia transmission, testing and sequelae. Women indicated a high level of acceptance and support for chlamydia screening, expressing their willingness to undertake whatever care was necessary to ensure the health of their baby. There was a strong preference for urine testing over other methods of specimen collection. Women questioned why testing was not already conducted alongside other antenatal STI screening tests, particularly in view of the risks chlamydia poses to the baby. Women who tested positive for chlamydia had mixed reactions, however, most felt relief and gratitude at having had chlamydia detected and reported high levels of partner support.</p> <p>Conclusions</p> <p>Chlamydia screening as part of routine antenatal care was considered highly acceptable among young pregnant women who recognized the benefits of screening and strongly supported its implementation as part of routine antenatal care. The acceptability of screening is important to the uptake of chlamydia screening in future antenatal screening strategies.</p

    Cognitive interviewing of the US National Cancer Institute’s Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)

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    The National Cancer Institute’s Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) is a library of question items that enables patient reporting of adverse events (AEs) in clinical trials. This study contributes content validity evidence of the PRO-CTCAE by incorporating cancer patient input of the relevance and comprehensiveness of the item library

    Gender, gender role identity, and children's reported feelings toward the same and opposite sex

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    The present study explored the relative importance of gender role identity, gender role attitudes, and biological gender in determining the intensity of anger, disgust, hurt, envy, fear, pity, and liking reported toward same- and opposite-sex children. Sixty male and 60 female 6–12-year-old children reported on the intensity of emotions that a hypothetical child would experience toward same- and opposite-sex children in various situations. The Children's Personal Attitudes Questionnaire, the Children's Attitudes toward Women Scale, and a self-reported toy preference measure were used to assess gender role identity and attitudes. The results indicated that girls were more angry at males than at females, and that both sexes tended to be more hurt and disgusted by opposite-sex than by same-sex children. Girls also tended to report more fear than did boys, and both sexes tended to report more fear of males than of females. Most importantly, gender role identity and attitudes accounted for more of the variance in predicting the quality of reported emotions than did biological gender. Biological gender predicted to only one feeling: pity toward males, after the variance accounted for by the gender role traits was removed. In general, both boys and girls who scored highly on feminine gender role identity were both communal and vulnerable in their reported emotions (high in reported liking, fear, and hurt). Children's reported feelings toward the same- and opposite-sex children seemed to be based on the evaluation of whether other children's biological gender differed from the children's own gender role identity characteristics.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45596/1/11199_2004_Article_BF00289226.pd
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