732 research outputs found

    The self‐reference effect in attention deficit hyperactivity disorder

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    The self‐memory system depends on the prioritization and capture of self‐relevant information, so may be disrupted by difficulties in attending to, encoding and retrieving self‐relevant information. The current study compares memory for self‐referenced and other‐referenced items in children with ADHD and typically developing comparison groups matched for verbal and chronological age. Children aged 5–14 (N = 90) were presented with everyday objects alongside an own‐face image (self‐reference trials) or an unknown child's image (other‐referenced trials). They were asked whether the child shown would like the object, before completing a surprise source memory test. In a second task, children performed, and watched another person perform, a series of actions before their memory for the actions was tested. A significant self‐reference effect (SRE) was found in the typically developing children (i.e. both verbal and chronological age‐matched comparison groups) for the first task, with significantly better memory for self‐referenced than other‐referenced objects. However, children with ADHD showed no SRE, suggesting a compromised ability to bind information with the cognitive self‐concept. In the second task, all groups showed superior memory for actions carried out by the self, suggesting a preserved enactment effect in ADHD. Implications and applications for the self‐memory system in ADHD are discussed

    The Self Referent Effect in Attention Deficit Hyperactivity Disorder

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    The self-memory system depends on the prioritisation and capture of self-relevant information, so may be disrupted by difficulties in attending to, encoding and retrieving self-relevant information. The current study compares memory for self-referenced and other-referenced items in children with ADHD and typically-developing comparison groups matched for verbal and chronological age. Children aged 5-14 (N=90) were presented with everyday objects alongside an own-face image (self-reference trials) or an unknown child’s image (other-referenced trials). They were asked whether the child shown would like the object, before completing a surprise source memory test. In a second task, children performed, and watched another person perform, a series of actions before their memory for the actions was tested. A significant self-reference effect (SRE) was found in the typically-developing children (i.e., both verbal and chronological age-matched comparison groups) for the first task, with significantly better memory for self-referenced than other-referenced objects. However, children with ADHD showed no SRE, suggesting a compromised ability to bind information with the cognitive self-concept. In the second task, all groups showed superior memory for actions carried out by the self, suggesting a preserved enactment effect in ADHD. Implications and applications for the self-memory system in ADHD are discussed.<br/

    Particulate methane monooxygenase contains only mononuclear copper centers

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    Bacteria that oxidize methane to methanol are central to mitigating emissions of methane, a potent greenhouse gas. The nature of the copper active site in the primary metabolic enzyme of these bacteria, particulate methane monooxygenase (pMMO), has been controversial owing to seemingly contradictory biochemical, spectroscopic, and crystallographic results. We present biochemical and electron paramagnetic resonance spectroscopic characterization most consistent with two monocopper sites within pMMO: one in the soluble PmoB subunit at the previously assigned active site (CuB) and one ~2 nanometers away in the membrane-bound PmoC subunit (CuC). On the basis of these results, we propose that a monocopper site is able to catalyze methane oxidation in pMMO

    A life course model of self-rated health through adolescence and young adulthood

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    This paper proposes and tests a life course model of self-rated health (SRH) extending from late childhood to young adulthood, drawing on three waves of panel data from the U.S. National Longitudinal Study of Adolescent Health (Add Health). Very little research has examined SRH during the early decades, or whether and how these self-assessments reflect experiences in the family of origin. Background characteristics (parental education, income, and family structure), parental health conditions (asthma, diabetes, obesity, migraines), and early health challenges (physical abuse, presence of a disability, and parental alcoholism and smoking) predict SRH from adolescence to young adulthood. These experiences in the family-of-origin are substantially mediated by the young person’s health and health behaviors (as indicated by obesity, depression, smoking, drinking, and inactivity), although direct effects remain (especially for early health challenges). Associations between SRH and these mediators (especially obesity) strengthen with age. In turn, efforts to promote healthy behaviors in young adulthood, after the completion of secondary school, may be especially strategic in the promotion of health in later adulthood

    Parenting interventions for male young offenders: a review of the evidence on what works

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    Approximately one in four incarcerated male young offenders in the UK is an actual or expectant father. This paper reviews evidence on the effectiveness of parenting interventions for male young offenders. We conducted systematic searches across 20 databases and consulted experts. Twelve relevant evaluations were identified: 10 from the UK, of programmes for incarcerated young offenders, and two from the US, of programmes for young parolees. None used experimental methods or included a comparison group. They suggest that participants like the courses, find them useful, and the interventions may improve knowledge about, and attitudes to, parenting. Future interventions should incorporate elements of promising parenting interventions with young fathers in the community, for example, and/or with older incarcerated parents. Young offender fathers have specific developmental, rehabilitative, and contextual needs. Future evaluations should collect longer-term behavioural parent and child outcome data and should use comparison groups and, ideally, randomization

    The LKB1-AMPK-α1 signaling pathway triggers hypoxic pulmonary vasoconstriction downstream of mitochondria

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    International audienceHypoxic pulmonary vasoconstriction (HPV), which aids ventilation-perfusion matching in the lungs, is triggered by mechanisms intrinsic to pulmonary arterial smooth muscles. The unique sensitivity of these muscles to hypoxia is conferred by mitochondrial cytochrome c oxidase subunit 4 isoform 2, the inhibition of which has been proposed to trigger HPV through increased generation of mitochondrial reactive oxygen species. Contrary to this model, we have shown that the LKB1-AMPK-α1 signaling pathway is critical to HPV. Spectral Doppler ultrasound revealed that deletion of the AMPK-α1 catalytic subunit blocked HPV in mice during mild (8% O2) and severe (5% O2) hypoxia, whereas AMPK-α2 deletion attenuated HPV only during severe hypoxia. By contrast, neither of these genetic manipulations affected serotonin-induced reductions in pulmonary vascular flow. HPV was also attenuated by reduced expression of LKB1, a kinase that activates AMPK during energy stress, but not after deletion of CaMKK2, a kinase that activates AMPK in response to increases in cytoplasmic Ca2+ Fluorescence imaging of acutely isolated pulmonary arterial myocytes revealed that AMPK-α1 or AMPK-α2 deletion did not affect mitochondrial membrane potential during normoxia or hypoxia. However, deletion of AMPK-α1, but not of AMPK-α2, blocked hypoxia from inhibiting KV1.5, the classical "oxygen-sensing" K+ channel in pulmonary arterial myocytes. We conclude that LKB1-AMPK-α1 signaling pathways downstream of mitochondria are critical for the induction of HPV, in a manner also supported by AMPK-α2 during severe hypoxia

    Exposing the Interplay Between Enzyme Turnover, Protein Dynamics and the Membrane Environment in Monoamine Oxidase B

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    There is an increasing realization that structure-based drug design may show improved success rates by understanding the ensemble of conformations and sub-states accessible to an enzyme and how the environment affects this ensemble. Human monoamine oxidase B (MAO-B) catalyzes the oxidation of amines and is inhibited for the treatment of both Parkinson’s disease and depression. Despite its clinical importance, its catalytic mechanism remains unclear and routes to drugging this target would be valuable and relevant. Evidence of a radical in either the transition state or resting state of MAO-B is present throughout the literature, and is suggested to be a flavin semiquinone, a tyrosyl radical or both. Here we see evidence of a resting state flavin semiquinone, via absorption redox studies and electron paramagnetic resonance, suggesting that the anionic semiquinone is biologically relevant. Based on enzyme kinetic studies, enzyme variants and molecular dynamics simulations we find evidence for the crucial importance of the membrane environment in mediating the activity of MAO-B and that this mediation is related to effects on the protein dynamics of MAO-B. Further, our MD simulations identify a hitherto undescribed entrance for substrate binding, membrane modulated substrate access, and indications for half-site reactivity: only one active site is accessible to binding at a time. Our study combines both experimental and computational evidence to illustrate the subtle interplay between enzyme activity, protein dynamics and the immediate membrane environment. Understanding key biomedical enzymes to this level of detail will be crucial to inform strategies (and binding sites) for rational drug design for these drug targets

    Cotton breeding in Australia : meeting the challenges of the 21st century

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    The Commonwealth Scientific and Industrial Research Organisation (CSIRO) cotton breeding program is the sole breeding effort for cotton in Australia, developing high performing cultivars for the local industry which is worth∌AU$3 billion per annum. The program is supported by Cotton Breeding Australia, a Joint Venture between CSIRO and the program’s commercial partner, Cotton Seed Distributors Ltd. (CSD). While the Australian industry is the focus, CSIRO cultivars have global impact in North America, South America, and Europe. The program is unique compared with many other public and commercial breeding programs because it focuses on diverse and integrated research with commercial outcomes. It represents the full research pipeline, supporting extensive long-term fundamental molecular research; native and genetically modified (GM) trait development; germplasm enhancement focused on yield and fiber quality improvements; integration of third-party GM traits; all culminating in the release of new commercial cultivars. This review presents evidence of past breeding successes and outlines current breeding efforts, in the areas of yield and fiber quality improvement, as well as the development of germplasm that is resistant to pests, diseases and abiotic stressors. The success of the program is based on the development of superior germplasm largely through field phenotyping, together with strong commercial partnerships with CSD and Bayer CropScience. These relationships assist in having a shared focus and ensuring commercial impact is maintained, while also providing access to markets, traits, and technology. The historical successes, current foci and future requirements of the CSIRO cotton breeding program have been used to develop a framework designed to augment our breeding system for the future. This will focus on utilizing emerging technologies from the genome to phenome, as well as a panomics approach with data management and integration to develop, test and incorporate new technologies into a breeding program. In addition to streamlining the breeding pipeline for increased genetic gain, this technology will increase the speed of trait and marker identification for use in genome editing, genomic selection and molecular assisted breeding, ultimately producing novel germplasm that will meet the coming challenges of the 21st Century
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