1,451 research outputs found

    Exclusive neuronal expression of SUCLA2 in the human brain

    Get PDF
    SUCLA2 encodes the ATP-forming subunit (A-SUCL-) of succinyl-CoA ligase, an enzyme of the citric acid cycle. Mutations in SUCLA2 lead to a mitochondrial disorder manifesting as encephalomyopathy with dystonia, deafness and lesions in the basal ganglia. Despite the distinct brain pathology associated with SUCLA2 mutations, the precise localization of SUCLA2 protein has never been investigated. Here we show that immunoreactivity of A-SUCL- in surgical human cortical tissue samples was present exclusively in neurons, identified by their morphology and visualized by double labeling with a fluorescent Nissl dye. A-SUCL- immunoreactivity co-localized >99% with that of the d subunit of the mitochondrial F0-F1 ATP synthase. Specificity of the anti-A-SUCL- antiserum was verified by the absence of labeling in fibroblasts from a patient with a complete deletion of SUCLA2. A-SUCL- immunoreactivity was absent in glial cells, identified by antibodies directed against the glial markers GFAP and S100. Furthermore, in situ hybridization histochemistry demonstrated that SUCLA2 mRNA was present in Nissl-labeled neurons but not glial cells labeled with S100. Immunoreactivity of the GTP-forming subunit (G-SUCL-) encoded by SUCLG2, or in situ hybridization histochemistry for SUCLG2 mRNA could not be demonstrated in either neurons or astrocytes. Western blotting of post mortem brain samples revealed minor G-SUCL- immunoreactivity that was however, not upregulated in samples obtained from diabetic versus non-diabetic patients, as has been described for murine brain. Our work establishes that SUCLA2 is expressed exclusively in neurons in the human cerebral cortex

    Sex-linked mating strategies diverge with a manipulation of genital salience

    Get PDF
    Trivers (Sexual selection and the descent of man, Aldine-Atherton, Chicago, pp 136–179, 1972) proposed that evolutionary factors should favor divergent mating strategies for males versus females. Such differences may be less pronounced among human beings than other animals and social norms and sex roles are also pertinent influences. The present experiment (N = 133 college undergraduates, 74 female) sought to bypass some of these other influences. Participants were randomly assigned to a condition designed to increase attention to the genital region (a downward pointing arrow) or not (an upward pointing arrow). They then reported on their interest in short-term (e.g., a one-night stand) and long-term (e.g., a potential marital partner) mating opportunities. A theory-consistent three-way interaction occurred such that the genital salience manipulation primed a shorter-term reproductive strategy among men and a longer-term reproductive strategy among women. The results provide unique support for evolution-linked ideas about sex differences in the form of a role for bodily attention

    Observation of associated near-side and away-side long-range correlations in √sNN=5.02  TeV proton-lead collisions with the ATLAS detector

    Get PDF
    Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT

    The deuteron: structure and form factors

    Get PDF
    A brief review of the history of the discovery of the deuteron in provided. The current status of both experiment and theory for the elastic electron scattering is then presented.Comment: 80 pages, 33 figures, submited to Advances in Nuclear Physic

    Distinct Actin and Lipid Binding Sites in Ysc84 Are Required during Early Stages of Yeast Endocytosis

    Get PDF
    During endocytosis in S. cerevisiae, actin polymerization is proposed to provide the driving force for invagination against the effects of turgor pressure. In previous studies, Ysc84 was demonstrated to bind actin through a conserved N-terminal domain. However, full length Ysc84 could only bind actin when its C-terminal SH3 domain also bound to the yeast WASP homologue Las17. Live cell-imaging has revealed that Ysc84 localizes to endocytic sites after Las17/WASP but before other known actin binding proteins, suggesting it is likely to function at an early stage of membrane invagination. While there are homologues of Ysc84 in other organisms, including its human homologue SH3yl-1, little is known of its mode of interaction with actin or how this interaction affects actin filament dynamics. Here we identify key residues involved both in Ysc84 actin and lipid binding, and demonstrate that its actin binding activity is negatively regulated by PI(4,5)P2. Ysc84 mutants defective in their lipid or actin-binding interaction were characterized in vivo. The abilities of Ysc84 to bind Las17 through its C-terminal SH3 domain, or to actin and lipid through the N-terminal domain were all shown to be essential in order to rescue temperature sensitive growth in a strain requiring YSC84 expression. Live cell imaging in strains with fluorescently tagged endocytic reporter proteins revealed distinct phenotypes for the mutants indicating the importance of these interactions for regulating key stages of endocytosis

    Historical perspectives on pastoralism and land tenure transformation in Ngamiland, Botswana: What are the policy and institutional lessons?

    Get PDF
    Pastoral societies in dryland Africa continue to face changes to their pastoral systems. These systems are influenced by a range of historical factors but little use is made of this information to design policies that suit pastoralists’ landscapes. This article provides a synthesis of historical perspectives on pastoral land use and tenure transformations in Ngamiland, south of the Okavango Delta, Botswana. Little documentation of herders’ historical perspectives exists and less is known about how past experiences can be applied to sustainable pastoralism policies. In this article, current land use pressing issues are examined and analysed within the context of past experiences. We use a series of oral histories with key informants, focus group discussions, expert interviews and rangelands field observations. Ngamiland historical perspectives depict a pastoral landscape that has been shaped by a variety of factors; livestock diseases, Human-wildlife-conflicts, droughts, land tenure transformations associated with rangeland policies and the pastoral identity of the Ovaherero/Ovambanderu ethnic groups. Pastoralists have followed unique trajectories, specific to their rangeland conditions and socio-cultural context. Resilience to climate shocks and diseases has been weakened by inequitable patterns of control over rangeland resources. We recommend institutional diversity such that from experiences of the past, lessons can be drawn of the sort of processes and institutions required for pastoralism policies including targeted pastoralists’ adaptations. Using pastoralists to provide information, especially in the area of indigenous knowledge, strategies can be developed to link conservation of wildlife and rangelands with pastoral production by developing ecologically-sensitive low-volume tourism that pastoral communities can tap in to diversify their livelihoods

    Developing the principles of chair based exercise for older people: a modified Delphi study

    Get PDF
    Background Chair based exercise (CBE) is suggested to engage older people with compromised health and mobility in an accessible form of exercise. A systematic review looking at the benefits of CBE for older people identified a lack of clarity regarding a definition, delivery, purpose and benefits. This study aimed to utilise expert consensus to define CBE for older people and develop a core set of principles to guide practice and future research. Methods The framework for consensus was constructed through a team workshop identifying 42 statements within 7 domains. A four round electronic Delphi study with multi-disciplinary health care experts was undertaken. Statements were rated using a 5 point Likert scale of agreement and free text responses. A threshold of 70% agreement was used to determine consensus. Free text responses were analysed thematically. Between rounds a number of strategies (e.g., amended wording of statements, generation and removal of statements) were used to move towards consensus. Results 16 experts agreed on 46 statements over four rounds of consultation (Round 1: 22 accepted, 3 removed, 5 new and 17 modified; Round 2: 16 accepted, 0 removed, 4 new and 6 modified; Round 3: 4 accepted, 2 removed, 0 new and 4 modified; Round 4: 4 accepted, 0 removed, 0 new, 0 modified). Statements were accepted in all seven domains: the definition of CBE (5), intended users (3), potential benefits (8), structure (12), format (8), risk management (7) and evaluation (3). The agreed definition of CBE had five components: 1. CBE is primarily a seated exercise programme; 2. The purpose of using a chair is to promote stability in both sitting and standing; 3. CBE should be considered as part of a continuum of exercise for frail older people where progression is encouraged; 4. CBE should be used flexibly to respond to the changing needs of frail older people; and 5. Where possible CBE should be used as a starting point to progress to standing programmes. Conclusions Consensus has been reached on a definition and a set of principles governing CBE for older people; this provides clarity for implementation and future research about CBE

    Sustaining interventions in care homes initiated by quality improvement projects: a qualitative study

    Get PDF
    This article relates to a research study that included patients or members of the workforce as study participants from GP practices in Nottingham and Nottinghamshire.Introduction: Inadequate and varied quality of care in care homes has led to a proliferation of quality improvement (QI) projects. This study examined the sustainability of interventions initiated by such projects. Method: This qualitative study explored the sustainability of seven interventions initiated by three QI projects between 2016 and 2018 in UK care homes and explored the perceived influences to the sustainability of interventions. QI projects were followed up in 2019. Staff leading QI projects (n=9) and care home (n=21, from 13 care homes) and healthcare (n=2) staff took part in semi-structured interviews. Interventions were classified as sustained if the intervention was continued at the point of the study. Thematic analysis of interview data was performed, drawing on the Consolidated Framework for Sustainability (CFS), a 40-construct model of sustainability of interventions. Results: Three interventions were sustained and four interventions were not. Seven themes described perceptions around what influenced sustainability: monitoring outcomes and regular check-in; access to replacement intervention materials; staff willingness to dedicate time and effort towards interventions; continuity of staff and thorough handover/inductions in place for new staff; ongoing communication and awareness raising; perceived effectiveness; and addressing care home priorities. All study themes fell within 18 of the 40 CFS constructs. Discussion: Our findings resonate with the CFS and are also consistent with implementation theories, suggesting sustainability is best addressed during implementation rather than treated as a separate process which follows implementation. Commissioning and funding QI projects should address these considerations early on, during implementation
    corecore