864 research outputs found

    38th annual New England Intercollegiate Geological Excursion: Mount Washington, New Hampshire, October 5 and 6, 1946

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    Trip A: Percy Quadrangle: Trip B: Gorham and Mt. Washington quadrangles; Trip C: Northern part of Mt. Washington quadrangle; Trip D: Lower northern slopes of Mt. Adams and Mt. Madison; Trip E: Emergency trip

    Peripheral brain-derived neurotrophic factor contributes to chronic osteoarthritis joint pain

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    Brain-derived neurotrophic factor (BDNF) and the high-affinity receptor tropomyosin receptor kinase B (TrkB) have important roles in neuronal survival and in spinal sensitization mechanisms associated with chronic pain. Recent clinical evidence also supports a peripheral role of BDNF in osteoarthritis (OA), with synovial expression of TrkB associated with higher OA pain. The aim of this study was to use clinical samples and animal models to explore the potential contribution of knee joint BDNF/TrkB signalling to chronic OA pain. Brain-derived neurotrophic factor and TrkB mRNA and protein were present in knee synovia from OA patients (16 women, 14 men, median age 67 years [interquartile range: 61-73]). There was a significant positive correlation between mRNA expression of NTRK2 (TrkB) and the proinflammatory chemokine fractalkine in the OA synovia. Using the surgical medial meniscal transection (MNX) model and the chemical monosodium iodoacetate (MIA) model of OA pain in male rats, the effects of peripheral BDNF injection, vs sequestering endogenous BDNF with TrkB-Fc chimera, on established pain behaviour were determined. Intra-articular injection of BDNF augmented established OA pain behaviour in MIA rats, but had no effect in controls. Intra-articular injection of the TrkB-Fc chimera acutely reversed pain behaviour to a similar extent in both models of OA pain (weight-bearing asymmetry MIA: -11 ± 4%, MNX: -12 ± 4%), compared to vehicle treatment. Our data suggesting a contribution of peripheral knee joint BDNF/TrkB signalling in the maintenance of chronic OA joint pain support further investigation of the therapeutic potential of this target

    Cell type–specific super-resolution imaging reveals an increase in calcium-permeable AMPA receptors at spinal peptidergic terminals as an anatomical correlate of inflammatory pain

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    Spinal hyperexcitability is a key event in the development of persistent pain, and arises partly from alterations in the number and localization of α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)-type glutamate receptors. However, determining precisely where these changes occur is challenging due to the requirement for multiplex labelling and nanoscale resolution. The recent development of super-resolution light microscopy provides new tools to address these challenges. Here, we apply combined confocal/direct STochastic Optical Reconstruction Microscopy (dSTORM) to reveal changes in calcium-permeable subunits of AMPA-type glutamate receptors (GluA1) at identified spinal cord dorsal horn (SCDH) peptidergic axon terminals in a model of inflammatory pain. L4/5 lumbar spinal cord was collected from adult male C57BL/6J mice 24 hours after unilateral hind paw injection of saline or 1% carrageenan (n = 6/group). Tissue was immunolabelled for markers of peptidergic axon terminals (substance P; SP), presynaptic active zones (Bassoon), and GluA1. Direct stochastic optical reconstruction microscopy revealed a 59% increase in total GluA1 immunolabelling in the SCDH in the carrageenan group, which was not detected by confocal microscopy. Cell type–specific analyses identified a 10-fold increase in GluA1 localized to SP+ structures, and identified GluA1 nanodomains that scaled with behavioural hypersensitivity, and were associated with synaptic release sites. These findings demonstrate that dSTORM has the sensitivity and power to detect nanoscale anatomical changes in the SCDH, and provides new evidence for synaptic insertion of GluA1+-AMPA-Rs at spinal peptidergic nociceptive terminals in a model of inflammatory pain

    Magazine and reader constructions of 'metrosexuality' and masculinity: a membership categorisation analysis

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    Since the launch of men's lifestyle magazines in the 1980s, academic literature has predominantly focused on them as a cultural phenomenon arising from entrepreneurial and commercial initiatives and/or as cultural texts that proffer representations of masculinity such as 'new lad' and 'new dad'. This paper steps aside from the focus on culture and, instead, treats magazine content as a discursive space in which gender and sexuality are oriented to, negotiated, and accomplished within and beyond the magazine itself (i.e. through readers' responses). Specifically, membership categorisation analysis is deployed to explore how the relatively new (and perhaps alternative) category for men - 'metrosexual' - is presented and received. Our analysis suggests that masculinity concerns are central in debates about 'metrosexuality', with self-identified 'metrosexuals' invoking heterosexual prowess and self-respect on the one hand, and critics (e.g. selfidentified 'real men') lamenting 'metrosexuality' for its perceived effeminacy and lack of authenticity on the other. Implications for understanding contemporary masculinities are discussed

    Serum levels of hydroxylated metabolites of arachidonic acid cross-sectionally and longitudinally predict knee pain progression: an observational cohort study

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    Objective: To examine associations between serum oxylipins, which regulate tissue repair and pain signalling, and knee pain/radiographic osteoarthritis (OA) at baseline and knee pain at 3 year follow-up.Method: Baseline, and 3 year follow-up, knee pain phenotypes were assessed from 154 participants in the Knee Pain in the Community Cohort (KPIC) study. Serum and radiographic Kellgren and Lawrence (KL) and Nottingham line drawing atlas (NLDA) OA scores were collected at baseline. Oxylipin levels were quantified using liquid chromatography coupled with mass spectrometry (LC-MS/MS). Associations were measured by linear regression and Receiver Operator Characteristics (ROC).Results: Serum levels of 8,9-epoxyeicosatrienoic acid (EET) (β(95%CI)=1.809(-0.71-2.91)), 14,15-dihydroxyeicosatrienoic acid (DHET) (β(95%CI)=0.827(0.34-1.31)), and 12-hydroxyeicosatetraenoic acid (β(95%CI)=4.090(1.92-6.26)) and anandamide (β(95%CI)=3.060(1.35-4.77)) were cross-sectionally associated with current self-reported knee pain scores (NRS item 3, average pain). Serum levels of 9- (β(95%CI)=0.467(0.18-0.75)) & 15-hydroxyeicosatetraenoic acid (β(95%CI)=0.759(0.29-1.22)), 14-hydroxydocosahexaenoic acid (β(95%CI)=0.483(0.24-0.73)), and the ratio of 8,9-EET:DHET (β(95%CI)=0.510(0.19-0.82)) were cross-sectionally associated with K/L scores. Baseline serum concentrations of 8,9-EET (β(95%CI)=2.166(0.89-3.44)), 5,6-DHET (β(95%CI)=152.179(69.39-234.97)), and 5-HETE (β(95%CI)=1.724(0.677-2.77) showed positive longitudinal associations with follow-up knee pain scores (NRS item 3, average pain). Combined serum 8,9-EET and 5-HETE concentration showed the strongest longitudinal association (β(95%CI)=1.156(0.54-1.77) with pain scores at 3 years, and ROC curves distinguished between participants with no pain and high pain scores at follow-up (AUC(95%CI)=0.71(0.61-0.82)).Conclusions: Serum levels of a combination of hydroxylated metabolites of arachidonic acid may have prognostic utility for knee pain, providing a potential novel approach to identify people who are more likely to have debilitating pain in the future.Keywords: arachidonic acid; biomarkers; knee pain; osteoarthritis; oxylipins

    Search for displaced vertices arising from decays of new heavy particles in 7 TeV pp collisions at ATLAS

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    We present the results of a search for new, heavy particles that decay at a significant distance from their production point into a final state containing charged hadrons in association with a high-momentum muon. The search is conducted in a pp-collision data sample with a center-of-mass energy of 7 TeV and an integrated luminosity of 33 pb^-1 collected in 2010 by the ATLAS detector operating at the Large Hadron Collider. Production of such particles is expected in various scenarios of physics beyond the standard model. We observe no signal and place limits on the production cross-section of supersymmetric particles in an R-parity-violating scenario as a function of the neutralino lifetime. Limits are presented for different squark and neutralino masses, enabling extension of the limits to a variety of other models.Comment: 8 pages plus author list (20 pages total), 8 figures, 1 table, final version to appear in Physics Letters
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