1,754 research outputs found

    The Apoptosome Pathway to Caspase Activation in Primary Human Neutrophils Exhibits Dramatically Reduced Requirements for Cytochrome c

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    Caspase activation is a central event in numerous forms of apoptosis and results in the proteolytic degradation of multiple substrate proteins that contribute to the apoptotic phenotype. An important route to caspase activation proceeds via assembly of the “apoptosome” as a result of the cell stress–associated release of mitochondrial cytochrome c. Previous studies have shown that primary neutrophils are largely incapable of mitochondrial respiration, suggesting that these cells either lack functional mitochondria or possess a defective respiratory chain. This prompted us to examine whether neutrophils retain an intact cytochrome c/apoptotic protease-activating factor 1 (Apaf-1) pathway to caspase activation and apoptosis. We show that primary human neutrophils contain barely detectable levels of cytochrome c as well as other mitochondrial proteins. Surprisingly, neutrophil cell–free extracts readily supported Apaf-1–dependent caspase activation, suggesting that these cells may assemble cytochrome c–independent apoptosomes. However, further analysis revealed that the trace amount of cytochrome c present in neutrophils is both necessary and sufficient for Apaf-1–dependent caspase activation in these cells. Thus, neutrophils have a lowered threshold requirement for cytochrome c in the Apaf-1–dependent cell death pathway. These observations suggest that neutrophils retain cytochrome c for the purpose of assembling functional apoptosomes rather than for oxidative phosphorylation

    Musculoskeletal Pain:Current and Future Directions of Physical Therapy Practice

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    Musculoskeletal (MSK) pain is 1 of the most common problems managed by clinicians in MSK care. This article reviews current frameworks for the assessment and management of MSK pain within evidence-based physical therapy practice. Key considerations related to the biopsychosocial model of pain, evidence-based practice, assessment, treatment, physical activity/movement behavior, risk stratification, communication as well as patient education and self-management skills within physical therapy and physical and rehabilitation medicine are addressed. The future direction of MSK pain management is also discussed, including strategies to promote evidence-based practice, behavior change, social prescribing, and the use of technologies.status: Published onlin

    Design and development of an eHealth intervention to support self-management in people with musculoskeletal disorders - ‘eHealth: It’s TIME’: a study protocol [version 2; peer review: 2 approved]

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    Background: Musculoskeletal disorders (MSDs) are a leading cause of global morbidity, with the burden expected to increase in the near future. Self-management, with the support of healthcare professionals, is recommended for many MSDs. However, frequent clinical contact is not feasible. Previous research has highlighted the need for a co-designed eHealth-mediated self-management follow-up support intervention which integrates remote monitoring and behavioural change. Thus, the current study aims to develop and design a user-centred, eHealth-mediated self-management support prototype for people with MSDs. Methods: A three-step, iterative system development cycle will be utilised to develop and design the “eHealth: It’s TIME prototype”. The three-step process will include creating website features and content using two sequential focus groups with people with MSDs (n = 6 – 8); heuristic testing using the 10 heuristic principles of Nielsen (n = 5); and usability testing through in-person 60-minute interviews with people with MSDs (n = 3 – 5) and musculoskeletal physiotherapists (n = 3 – 5). Conclusion: The eHealth: It’s TIME prototype will be a systematically developed, follow-up self-management support intervention guided by behavioural change theory and the preferences of end users

    Quark helicity distributions from longitudinal spin asymmetries in muon-proton and muon-deuteron scattering

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    Double-spin asymmetries for production of charged pions and kaons in semi-inclusive deep-inelastic muon scattering have been measured by the COMPASS experiment at CERN. The data, obtained by scattering a 160 GeV muon beam off a longitudinally polarised NH_3 target, cover a range of the Bjorken variable x between 0.004 and 0.7. A leading order evaluation of the helicity distributions for the three lightest quarks and antiquark flavours derived from these asymmetries and from our previous deuteron data is presented. The resulting values of the sea quark distributions are small and do not show any sizable dependence on x in the range of the measurements. No significant difference is observed between the strange and antistrange helicity distributions, both compatible with zero. The integrated value of the flavour asymmetry of the helicity distribution of the light-quark sea, \Delta u-bar - \Delta d-bar, is found to be slightly positive, about 1.5 standard deviations away from zero.Comment: 13 pages, 5 figure

    The Deuteron Spin-dependent Structure Function g1d and its First Moment

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    We present a measurement of the deuteron spin-dependent structure function g1d based on the data collected by the COMPASS experiment at CERN during the years 2002-2004. The data provide an accurate evaluation for Gamma_1^d, the first moment of g1d(x), and for the matrix element of the singlet axial current, a0. The results of QCD fits in the next to leading order (NLO) on all g1 deep inelastic scattering data are also presented. They provide two solutions with the gluon spin distribution function Delta G positive or negative, which describe the data equally well. In both cases, at Q^2 = 3 (GeV/c)^2 the first moment of Delta G is found to be of the order of 0.2 - 0.3 in absolute value.Comment: fits redone using MRST2004 instead of MRSV1998 for G(x), correlation matrix adde

    Spin asymmetry A_1^d and the spin-dependent structure function g_1^d of the deuteron at low values of x and Q^2

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    We present a precise measurement of the deuteron longitudinal spin asymmetry A_1^d and of the deuteron spin-dependent structure function g_1^d at Q^2 < 1 GeV^2 and 4*10^-5 < x < 2.5*10^-2 based on the data collected by the COMPASS experiment at CERN during the years 2002 and 2003. The statistical precision is tenfold better than that of the previous measurement in this region. The measured A_1^d and g_1^d are found to be consistent with zero in the whole range of x.Comment: 17 pages, 10 figure