The association between pain diagram area, fear-avoidance beliefs, and pain catastrophising

BACKGROUND: The development of clinical practice guidelines for managing spinal pain have been informed by a biopsychosocial framework which acknowledges that pain arises from a combination of psychosocial and biomechanical factors. There is an extensive body of evidence that has associated various psychosocial factors with an increased risk of experiencing persistent pain. Clinicians require instruments that are brief, easy to administer and score, and capable of validly identifying psychosocial factors. The pain diagram is potentially such an instrument. The aim of our study was to examine the association between pain diagram area and psychosocial factors. METHODS: 183 adults, aged 20–85, with spinal pain were recruited. We administered a demographic checklist; pain diagram; 11-point Numerical Rating Scale assessing pain intensity; Pain Catastrophising Scale (PCS); MOS 36 Item Short Form Health Survey (SF-36); and the Fear Avoidance Beliefs Questionnaire (FABQ). Open source software, GIMP, was used to calculate the total pixilation area on each pain diagram. Linear regression was used to examine the relationship between pain diagram area and the following variables: age; gender; pain intensity; PCS total score; FABQ-Work scale score; FABQ-Activity scale score; and SF-36 Mental Health scale score. RESULTS: There were no significant associations between pain diagram area and any of the clinical variables. CONCLUSION: Our findings showed that that pain diagram area was not a valid measure to identify psychosocial factors. Several limitations constrained our results and further studies are warranted to establish if pain diagram area can be used assess psychosocial factors

A low density of 0.8 g/cc for the Trojan binary asteroid 617 Patroclus

The Trojan population consists of two swarms of asteroids following the same orbit as Jupiter and located at the L4 and L5 Lagrange points of the Jupiter-Sun system (leading and following Jupiter by 60 degrees). The asteroid 617 Patroclus is the only known binary Trojan (Merline et al. 2001). The orbit of this double system was hitherto unknown. Here we report that the components, separated by 680 km, move around the system centre of mass, describing roughly a circular orbit. Using the orbital parameters, combined with thermal measurements to estimate the size of the components, we derive a very low density of 0.8 g/cc. The components of Patroclus are therefore very porous or composed mostly of water ice, suggesting that they could have been formed in the outer part of the solar system.Comment: 10 pages, 3 figures, 1 tabl

Neurodevelopmental and neuropsychiatric behaviour defects arise from 14-3-3ζ deficiency.

Complex neuropsychiatric disorders are believed to arise from multiple synergistic deficiencies within connected biological networks controlling neuronal migration, axonal pathfinding and synapse formation. Here, we show that deletion of 14-3-3ζ causes neurodevelopmental anomalies similar to those seen in neuropsychiatric disorders such as schizophrenia, autism spectrum disorder and bipolar disorder. 14-3-3ζ-deficient mice displayed striking behavioural and cognitive deficiencies including a reduced capacity to learn and remember, hyperactivity and disrupted sensorimotor gating. These deficits are accompanied by subtle developmental abnormalities of the hippocampus that are underpinned by aberrant neuronal migration. Significantly, 14-3-3ζ-deficient mice exhibited abnormal mossy fibre navigation and glutamatergic synapse formation. The molecular basis of these defects involves the schizophrenia risk factor, DISC1, which interacts isoform specifically with 14-3-3ζ. Our data provide the first evidence of a direct role for 14-3-3ζ deficiency in the aetiology of neurodevelopmental disorders and identifies 14-3-3ζ as a central risk factor in the schizophrenia protein interaction network

Observations of DG Tauri with the Keck Interferometer

We present the first science results from the Keck Interferometer, a direct-detection infrared interferometer utilizing the two 10-meter Keck telescopes. The instrument and system components are briefly described. We then present observations of the T Tauri object DG Tau, which is resolved by the interferometer. The resolved component has a radius of 0.12 to 0.24 AU, depending on the assumed stellar and extended component fluxes and the model geometry used. Possible origins and implications of the resolved emission are discussed.Comment: 10 pages, 2 figures, to appear in ApJ Letter

A dual role for the N-terminal domain of the IL-3 receptor in cell signalling

The interleukin-3 (IL-3) receptor is a cell-surface heterodimer that links the haemopoietic, vascular and immune systems and is overexpressed in acute and chronic myeloid leukaemia progenitor cells. It belongs to the type I cytokine receptor family in which the α-subunits consist of two fibronectin III-like domains that bind cytokine, and a third, evolutionarily unrelated and topologically conserved, N-terminal domain (NTD) with unknown function. Here we show by crystallography that, while the NTD of IL3Rα is highly mobile in the presence of IL-3, it becomes surprisingly rigid in the presence of IL-3 K116W. Mutagenesis, biochemical and functional studies show that the NTD of IL3Rα regulates IL-3 binding and signalling and reveal an unexpected role in preventing spontaneous receptor dimerisation. Our work identifies a dual role for the NTD in this cytokine receptor family, protecting against inappropriate signalling and dynamically regulating cytokine receptor binding and function.Sophie E. Broughton, Timothy R. Hercus, Tracy L. Nero, Winnie L. Kan ... Timothy P. Hughes, Angel F. Lopez ... et al

Perverted responses of the human granulocyte-macrophage colony-stimulating factor receptor in mouse cell lines due to cross-species b-subunit association

Transfected murine cell lines are commonly used to study the function of many human cytokine or receptor mutants. This study reports the inappropriate activation of the human granulocyte-macrophage colony-stimulating factor (hGM-CSF) receptor by the human GM-CSF antagonist, E21R, when the human receptor is introduced into the murine cell line BaF-B03. E21R-induced proliferation of the BaF-B03 cells is dependent on transfection with both hGM-CSF receptor alpha and beta(c) subunits. Studies on the underlying mechanism revealed constitutive association between human and mouse beta(c) and GM-CSF receptor-alpha, tyrosine phosphorylation of mouse and human beta(c), and association of phosphorylated mouse beta(c) into an activated human GM-CSF receptor complex in response to E21R and GM-CSF. This interspecies receptor cross-talk of receptor signaling subunits may produce misleading results and emphasizes the need to use cell lines devoid of the cognate endogenous receptors for functional analysis of ligand and receptor mutants

The dimeric versus monomeric status of 14-3-3z is controlled by phosphorylation of Ser58 at the dimer interface

The 14-3-3 proteins play a central role in the regulation of cell growth, cycling, and apoptosis by modulating the functional activities of key signaling proteins. Through binding to a phosphoserine motif, 14-3-3 alters target proteins activities by sequestering them, relocalizing them, conformationally altering their functional activity, or by promoting interaction with other proteins. These functions of 14-3-3 are facilitated by, if not dependent on, its dimeric structure. We now show that the dimeric status of 14-3-3 is regulated by site-specific serine phosphorylation. We found that a sphingosine-dependent kinase phosphorylates 14-3-3 in vitro and in vivo on a serine residue (Ser58) located within the dimer interface. Furthermore, by developing an antibody that specifically recognizes 14-3-3zeta phosphorylated on Ser58 and employing native-PAGE and cross-linking techniques, we found that 14-3-3 phosphorylated on Ser58 is monomeric both in vitro and in vivo. Phosphorylated 14-3-3 was detected solely as a monomer, indicating that phosphorylation of a single monomer within a dimer is sufficient to disrupt the dimeric structure. Significantly, phosphorylation-induced monomerization did not prevent 14-3-3 binding to a phosphopeptide target. We propose that this regulated monomerization of 14-3-3 controls its ability to modulate the activity of target proteins and thus may have significant implications for 14-3-3 function and the regulation of many cellular processes.Joanna M. Woodcock, Jane Murphy, Frank C. Stomski, Michael C. Berndt, and Angel F. Lope