Suprathreshold heat pain response predicts activity-related pain, but not rest-related pain, in an exercise-induced injury model

© 2014 Coronado et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Exercise-induced injury models are advantageous for studying pain since the onset of pain is controlled and both pre-injury and post-injury factors can be utilized as explanatory variables or predictors. In these studies, rest-related pain is often considered the primary dependent variable or outcome, as opposed to a measure of activity-related pain. Additionally, few studies include pain sensitivity measures as predictors. In this study, we examined the influence of pre-injury and post-injury factors, including pain sensitivity, for induced rest and activity-related pain following exercise induced muscle injury. The overall goal of this investigation was to determine if there were convergent or divergent predictors of rest and activityrelated pain. One hundred forty-three participants provided demographic, psychological, and pain sensitivity information and underwent a standard fatigue trial of resistance exercise to induce injury of the dominant shoulder. Pain at rest and during active and resisted shoulder motion were measured at 48- and 96-hours post-injury. Separate hierarchical models were generated for assessing the influence of pre-injury and post-injury factors on 48- and 96-hour rest-related and activityrelated pain. Overall, we did not find a universal predictor of pain across all models. However, pre-injury and post-injury suprathreshold heat pain response (SHPR), a pain sensitivity measure, was a consistent predictor of activity-related pain, even after controlling for known psychological factors. These results suggest there is differential prediction of pain. A measure of pain sensitivity such as SHPR appears more influential for activity-related pain, but not rest-related pain, and may reflect different underlying processes involved during pain appraisal

Opening a new window to other worlds with spectropolarimetry

A high level of diversity has already been observed among the planets of our own Solar System. As such, one expects extrasolar planets to present a wide range of distinctive features, therefore the characterisation of Earth- and super Earth-like planets is becoming of key importance in scientific research. The SEARCH (Spectropolarimetric Exoplanet AtmospheRe CHaracerisation) mission proposal of this paper represents one possible approach to realising these objectives. The mission goals of SEARCH include the detailed characterisation of a wide variety of exoplanets, ranging from terrestrial planets to gas giants. More specifically, SEARCH will determine atmospheric properties such as cloud coverage, surface pressure and atmospheric composition, and may also be capable of identifying basic surface features. To resolve a planet with a semi major axis of down to 1.4AU and 30pc distant SEARCH will have a mirror system consisting of two segments, with elliptical rim, cut out of a parabolic mirror. This will yield an effective diameter of 9 meters along one axis. A phase mask coronagraph along with an integral spectrograph will be used to overcome the contrast ratio of star to planet light. Such a mission would provide invaluable data on the diversity present in extrasolar planetary systems and much more could be learned from the similarities and differences compared to our own Solar System. This would allow our theories of planetary formation, atmospheric accretion and evolution to be tested, and our understanding of regions such as the outer limit of the Habitable Zone to be further improved.Comment: 23 pages, accepted for publication in Experimental Astronom

Cytokinesis in bloodstream stage Trypanosoma brucei requires a family of katanins and spastin

Microtubule severing enzymes regulate microtubule dynamics in a wide range of organisms and are implicated in important cell cycle processes such as mitotic spindle assembly and disassembly, chromosome movement and cytokinesis. Here we explore the function of several microtubule severing enzyme homologues, the katanins (KAT80, KAT60a, KAT60b and KAT60c), spastin (SPA) and fidgetin (FID) in the bloodstream stage of the African trypanosome parasite, Trypanosoma brucei. The trypanosome cytoskeleton is microtubule based and remains assembled throughout the cell cycle, necessitating its remodelling during cytokinesis. Using RNA interference to deplete individual proteins, we show that the trypanosome katanin and spastin homologues are non-redundant and essential for bloodstream form proliferation. Further, cell cycle analysis revealed that these proteins play essential but discrete roles in cytokinesis. The KAT60 proteins each appear to be important during the early stages of cytokinesis, while downregulation of KAT80 specifically inhibited furrow ingression and SPA depletion prevented completion of abscission. In contrast, RNA interference of FID did not result in any discernible effects. We propose that the stable microtubule cytoskeleton of T. brucei necessitates the coordinated action of a family of katanins and spastin to bring about the cytoskeletal remodelling necessary to complete cell divisio

Generation and characterization of antibodies specific for caspase-cleaved neo-epitopes: a novel approach

Apoptosis research has been significantly aided by the generation of antibodies against caspase-cleaved peptide neo-epitopes. However, most of these antibodies recognize the N-terminal fragment and are specific for the protein in question. The aim of this project was to create antibodies, which could identify caspase-cleaved proteins without a priori knowledge of the cleavage sites or even the proteins themselves. We hypothesized that many caspase-cleavage products might have a common antigenic shape, given that they must all fit into the same active site of caspases. Rabbits were immunized with the eight most prevalent exposed C-terminal tetrapeptide sequences following caspase cleavage. After purification of the antibodies we demonstrated (1) their specificity for exposed C-terminal (but not internal) peptides, (2) their ability to detect known caspase-cleaved proteins from apoptotic cell lysates or supernatants from apoptotic cell culture and (3) their ability to detect a caspase-cleaved protein whose tetrapeptide sequence differs from the eight tetrapeptides used to generate the antibodies. These antibodies have the potential to identify novel neo-epitopes produced by caspase cleavage and so can be used to identify pathway-specific caspase cleavage events in a specific cell type. Additionally this methodology may be applied to generate antibodies against products of other proteases, which have a well-defined and non-promiscuous cleavage activity

A rocky composition for an Earth-sized exoplanet

Planets with sizes between that of Earth (with radius R[subscript circle in cross]) and Neptune (about 4 R[subscript circle in cross]) are now known to be common around Sun-like stars. Most such planets have been discovered through the transit technique, by which the planet’s size can be determined from the fraction of starlight blocked by the planet as it passes in front of its star. Measuring the planet’s mass—and hence its density, which is a clue to its composition—is more difficult. Planets of size 2–4 R[subscript circle in cross] have proved to have a wide range of densities, implying a diversity of compositions, but these measurements did not extend to planets as small as Earth. Here we report Doppler spectroscopic measurements of the mass of the Earth-sized planet Kepler-78b, which orbits its host star every 8.5 hours (ref. 6). Given a radius of 1.20 ± 0.09 R[subscript circle in cross] and a mass of 1.69 ± 0.41 M[subscript circle in cross], the planet’s mean density of 5.3 ± 1.8 g cm[superscript −3] is similar to Earth’s, suggesting a composition of rock and iron.Kepler Participating Scientist Progra

Expression of Distal-less, dachshund, and optomotor blind in Neanthes arenaceodentata (Annelida, Nereididae) does not support homology of appendage-forming mechanisms across the Bilateria

The similarity in the genetic regulation of arthropod and vertebrate appendage formation has been interpreted as the product of a plesiomorphic gene network that was primitively involved in bilaterian appendage development and co-opted to build appendages (in modern phyla) that are not historically related as structures. Data from lophotrochozoans are needed to clarify the pervasiveness of plesiomorphic appendage forming mechanisms. We assayed the expression of three arthropod and vertebrate limb gene orthologs, Distal-less (Dll), dachshund (dac), and optomotor blind (omb), in direct-developing juveniles of the polychaete Neanthes arenaceodentata. Parapodial Dll expression marks premorphogenetic notopodia and neuropodia, becoming restricted to the bases of notopodial cirri and to ventral portions of neuropodia. In outgrowing cephalic appendages, Dll activity is primarily restricted to proximal domains. Dll expression is also prominent in the brain. dac expression occurs in the brain, nerve cord ganglia, a pair of pharyngeal ganglia, presumed interneurons linking a pair of segmental nerves, and in newly differentiating mesoderm. Domains of omb expression include the brain, nerve cord ganglia, one pair of anterior cirri, presumed precursors of dorsal musculature, and the same pharyngeal ganglia and presumed interneurons that express dac. Contrary to their roles in outgrowing arthropod and vertebrate appendages, Dll, dac, and omb lack comparable expression in Neanthes appendages, implying independent evolution of annelid appendage development. We infer that parapodia and arthropodia are not structurally or mechanistically homologous (but their primordia might be), that Dll’s ancestral bilaterian function was in sensory and central nervous system differentiation, and that locomotory appendages possibly evolved from sensory outgrowths

Comparison of outcomes of percutaneous coronary intervention on proximal versus non-proximal left anterior descending coronary artery, proximal left circumflex, and proximal right coronary artery: A cross-sectional study

BACKGROUND: Previous studies have shown that lesions in proximal left anterior descending coronary artery (LAD) may develop more restenosis after balloon angioplasty than lesions in other coronary segments. However, stenting seems to have reduced this gap. In this study, we compared outcomes of percutaneous coronary intervention (PCI) on proximal LAD versus proximal left circumflex (LCX) or right coronary artery (RCA) and proximal versus non-proximal LAD. METHODS: From 1737 patients undergoing PCI between March 2004 and 2005, those with cardiogenic shock, primary PCI, total occlusions, and multivessel or multi-lesion PCI were excluded. Baseline characteristics and in-hospital outcomes were compared in 408 patients with PCI on proximal LAD versus 133 patients with PCI on proximal LCX/RCA (study I) and 244 patients with PCI on non-proximal LAD (study II). From our study populations, 449 patients in study I and 549 patients in study II participated in complete follow-up programs, and long-term PCI outcomes were compared within these groups. The statistical methods included Chi-square or Fisher's exact test, student's t-test, stratification methods, multivariate logistic regression and Cox proportional hazards model. RESULTS: In the proximal LAD vs. proximal LCX/RCA groups, smoking and multivessel disease were less frequent and drug-eluting stents were used more often (p = 0.01, p < 0.001, and p < 0.001, respectively). Patients had longer and smaller-diameter stents (p = 0.009, p < 0.001, respectively). In the proximal vs. non-proximal LAD groups, multivessel disease was less frequent (p = 0.05). Patients had larger reference vessel diameters (p < 0.001) and were more frequently treated with stents, especially direct stenting technique (p < 0.001). Angiographic success rate was higher in the proximal LAD versus proximal LCX/RCA and non-proximal LAD groups (p = 0.004 and p = 0.05, respectively). In long-term follow-up, major adverse cardiac events showed no difference. After statistical adjustment for significant demographic, angiographic or procedural characteristics, long-term PCI outcomes were still similar in the proximal LAD versus proximal LCX/RCA and non-proximal LAD groups. CONCLUSION: Despite the known worse prognosis of proximal LAD lesions, in the era of stenting, our long-term outcomes were similar in patients with PCI on proximal LAD versus proximal LCX/RCA and non-proximal LAD. Furthermore, we had better angiographic success rates in patients with PCI on proximal LAD