HLA-DRB1*03 is strongly associated with anti-Jo-1-positive idiopathic inflammatory myopathies (IIM) and there is now increasing evidence that Jo-1 antigen is preferentially expressed in lung tissue. ...This study examined whether smoking was associated with the development of anti-Jo-1 antibodies in HLA-DRB1*03-positive IIM.
IIM cases were selected with concurrent information regarding HLA-DRB1 status, smoking history and anti-Jo-1 antibody status. DNA was genotyped at DRB1 using a commercial sequence-specific oligonucleotide kit. Anti-Jo-1 antibody status was established using a line blot assay or immunoprecipitation.
557 Caucasian IIM patients were recruited from Hungary (181), UK (99), Sweden (94) and Czech Republic (183). Smoking frequency was increased in anti-Jo-1-positive IIM cases, and reached statistical significance in Hungarian IIM (45% Jo-1-positive vs 17% Jo-1-negative, OR 3.94, 95% CI 1.53 to 9.89, p<0.0001). A strong association between HLA-DRB1*03 and anti-Jo-1 status was observed across all four cohorts (DRB1*03 frequency: 74% Jo-1-positive vs 35% Jo-1-negative, OR 5.55, 95% CI 3.42 to 9.14, p<0.0001). The frequency of HLA-DRB1*03 was increased in smokers. The frequency of anti-Jo-1 was increased in DRB1*03-positive smokers vs DRB1*03-negative non-smokers (42% vs 8%, OR 7.75, 95% CI 4.21 to 14.28, p<0.0001) and DRB1*03-positive non-smokers (42% vs 31%, p=0.08). In DRB1*03-negative patients, anti-Jo-1 status between smokers and non-smokers was not significantly different. No significant interaction was noted between smoking and DRB1*03 status using anti-Jo-1 as the outcome measure.
Smoking appears to be associated with an increased risk of possession of anti-Jo-1 in HLA-DRB1*03-positive IIM cases. The authors hypothesise that an interaction between HLA-DRB1*03 and smoking may prime the development of anti-Jo-1 antibodies.
Trophic cascades have been documented in a diversity of ecological systems and can be important in determining biomass distribution within a community. To date, the literature on trophic cascades has ...focused on whether and in which systems cascades occur. Many biological (e.g., productivity : biomass ratios) and methodological (e.g., experiment size or duration) factors vary with the ecosystem in which data were collected, but ecosystem type, per se, does not provide mechanistic insights into factors controlling cascade strength. Here, we tested various hypotheses about why trophic cascades occur and what determines their magnitude using data from 114 studies that measured the indirect trophic effects of predators on plant community biomass in seven aquatic and terrestrial ecosystems. Using meta-analysis, we examined the relationship between the indirect effect of predator manipulation on plants and 18 biological and methodological factors quantified from these studies. We found, in contrast to predictions, that high system productivity and low species diversity do not consistently generate larger trophic cascades. A combination of herbivore and predator metabolic factors and predator taxonomy (vertebrate vs. invertebrate) explained 31% of the variation in cascade strength among all 114 studies. Within systems, 18% of the variation in cascade strength was explained with similar predator and herbivore characteristics. Within and across all systems, the strongest cascades occurred in association with invertebrate herbivores and endothermic vertebrate predators. These associations may result from a combination of true biological differences among species with different physiological requirements and bias among organisms studied in different systems. Thus, although cascade strength can be described by biological characteristics of predators and herbivores, future research on indirect trophic effects must further examine biological and methodological differences among studies and systems.
Autoantibodies to a novel autoantigen small ubiquitin-like modifier activating enzyme (SAE) associated with dermatomyositis (DM) have previously been identified. The aim of this study was to ...establish the frequency of anti-SAE autoantibodies in a UK myositis cohort and investigate clinicoimmunogenetic associations.
Clinical data and sera were studied from 266 patients recruited to the Adult Onset Myositis Immunogenetic Collaboration. Myositis sera, control sera including 250 patients with other connective tissue diseases and 50 healthy participants were screened using radio-immunoprecipitation. Immunodepletion was performed on all sera immunoprecipitating 40 and 90 kDa bands to confirm the presence of anti-SAE. DNA from 202 patients with myositis was genotyped for human leucocyte antigen (HLA)-DRB1 and DQB1; DQA1 data were inferred.
Out of 266 patients with myositis, 11 (4%) were positive for anti-SAE, which was found exclusively in DM with a frequency of 8%. Patients with anti-SAE had a high frequency of cutaneous lesions including heliotrope (82%) and Gottron rash (82%). Of the 11, 9 (82%) had systemic features and 7 of 9 (78%) developed dysphagia. Of those nine, seven (78%) presented with skin disease before myositis onset. All patients with anti-SAE possessed at least one copy of HLA-DQB1*03. HLA-DRB1*04-DQA1*03-DQB1*03 was a significant risk factor in anti-SAE positive versus patients who were anti-SAE negative (haplotype frequency 18% vs 6%, p<0.001, OR 5.7, 95% CI 1.9 to 17.3).
Anti-SAE is a myositis-specific autoantibody that identifies a subset of patients with adult DM. The majority of patients with anti-SAE presented with cutaneous disease and progressed to myositis with systemic features including dysphagia. This novel autoantibody has a strong association with the HLA-DRB1*04-DQA1*03-DQB1*03 haplotype.
The chemical senses are crucial for squamates (lizards and snakes). The extent to which squamates utilize their chemosensory system, however, varies greatly among taxa and species’ foraging ...strategies, and played an influential role in squamate evolution. In lizards, ‘Scleroglossa’ evolved a state where species use chemical cues to search for food (active foragers), whereas ‘Iguania’ retained the use of vision to hunt prey (ambush foragers). However, such strict dichotomy is flawed as shifts in foraging modes have occurred in all clades. Here, we attempted to disentangle effects of foraging ecology from phylogenetic trait conservatism as leading cause of the disparity in chemosensory investment among squamates. To do so, we used species’ tongue‐flick rate (TFR) in the absence of ecological relevant chemical stimuli as a proxy for its fundamental level of chemosensory investigation, that is baseline TFR. Based on literature data of nearly 100 species and using phylogenetic comparative methods, we tested whether and how foraging mode and diet affect baseline TFR. Our results show that baseline TFR is higher in active than ambush foragers. Although baseline TFRs appear phylogenetically stable in some lizard taxa, that is a consequence of concordant stability of foraging mode: when foraging mode shifts within taxa, so does baseline TFR. Also, baseline TFR is a good predictor of prey chemical discriminatory ability, as we established a strong positive relationship between baseline TFR and TFR in response to prey. Baseline TFR is unrelated to diet. Essentially, foraging mode, not phylogenetic relatedness, drives convergent evolution of similar levels of squamate chemosensory investigation.
We present experimental results from the first systematic study of performance scaling with drive parameters for a magnetoinertial fusion concept. In magnetized liner inertial fusion experiments, the ...burn-averaged ion temperature doubles to 3.1 keV and the primary deuterium-deuterium neutron yield increases by more than an order of magnitude to 1.1 × 1013 (2 kJ deuterium-tritium equivalent) through a simultaneous increase in the applied magnetic field (from 10.4 to 15.9 T), laser preheat energy (from 0.46 to 1.2 kJ), and current coupling (from 16 to 20 MA). Individual parametric scans of the initial magnetic field and laser preheat energy show the expected trends, demonstrating the importance of magnetic insulation and the impact of the Nernst effect for this concept. A drive-current scan shows that present experiments operate close to the point where implosion stability is a limiting factor in performance, demonstrating the need to raise fuel pressure as drive current is increased. Simulations that capture these experimental trends indicate that another order of magnitude increase in yield on the Z facility is possible with additional increases of input parameters.
Osteoarthritis affects the whole joint structure with progressive changes in cartilage, menisci, ligaments and subchondral bone, and synovial inflammation. Biomarkers are being developed to quantify ...joint remodelling and disease progression. This article was prepared following a working meeting of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis convened to discuss the value of biochemical markers of matrix metabolism in drug development in osteoarthritis. The best candidates are generally molecules or molecular fragments present in cartilage, bone or synovium and may be specific to one type of joint tissue or common to them all. Many currently investigated biomarkers are associated with collagen metabolism in cartilage or bone, or aggrecan metabolism in cartilage. Other biomarkers are related to non-collagenous proteins, inflammation and/or fibrosis. Biomarkers in osteoarthritis can be categorised using the burden of disease, investigative, prognostic, efficacy of intervention, diagnostic and safety classification. There are a number of promising candidates, notably urinary C-terminal telopeptide of collagen type II and serum cartilage oligomeric protein, although none is sufficiently discriminating to differentiate between individual patients and controls (diagnostic) or between patients with different disease severities (burden of disease), predict prognosis in individuals with or without osteoarthritis (prognostic) or perform so consistently that it could function as a surrogate outcome in clinical trials (efficacy of intervention). Future avenues for research include exploration of underlying mechanisms of disease and development of new biomarkers; technological development; the 'omics' (genomics, metabolomics, proteomics and lipidomics); design of aggregate scores combining a panel of biomarkers and/or imaging markers into single diagnostic algorithms; and investigation into the relationship between biomarkers and prognosis.
The distance separating predator and prey when the predator begins to approach, starting distance, was recently shown to affect flight initiation distance in many bird species, raising questions ...about the effect's generality, variation with ecological factors, and economic basis. I studied the effect in two lizard species that forage by ambush and escape into nearby refuges. Monitoring costs during approach are absent because ambushers remain immobile while scanning for prey and predators. Risks are minimized because of the proximity to refuge. Flight initiation distance increased weakly with starting distance in Sceloporus virgatus Smith, 1938 significantly only at rapid approach speed. It was not significant in Urosaurus ornatus (Baird and Girard, 1852) at slow approach speed. Flight initiation distance is predicted to increase with starting distance, owing to monitoring costs and assessment by prey of greater risk during prolonged approaches. The significant effect in S. virgatus, which lacks monitoring costs, is the first indication that risk affects the relationship between starting distance and flight initiation distance. Conditions in which starting distance is important and its possible effects in earlier studies are discussed, as well as standardizing approaches and possible artifactual effects of starting distance.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objectives:There is a known association between myositis and cancer. The risk is greater in dermatomyositis (DM) than polymyositis (PM), although reliable methods to predict cancer risk in specific ...patients with myositis are not presently available. This study was undertaken to determine whether risk of developing cancer in myositis can be predicted by antibody profiling.Methods:A cross-sectional study of UK Caucasian adults with PM (n = 109), DM (n = 103) and connective tissue disease overlap (myositis/CTD-overlap, n = 70). Patients were tested for a comprehensive range of myositis-specific/associated autoantibodies. Sensitivity and specificity analyses were performed for the optimal identification of cancer risk.Results:Sixteen patients had cancer-associated myositis (CAM) (15 DM, 1 myositis/CTD-overlap). CAM patients were older at disease onset, and patients without myositis-specific/associated autoantibodies on “routine” laboratory testing (negative for anti-Jo-1, anti-PM-Scl, anti-U1-RNP, anti-U3-RNP, anti-Ku antibodies) had a significantly increased risk of CAM. Possession of the antibody against 155 kDa and 140 kDa protein specificities (anti-155/140 antibody) represented a significant risk factor for CAM, and was found exclusively in DM. A positive anti-155/140 antibody result proved highly specific, moderately sensitive, with high negative predictive value for CAM. A “negative routine myositis antibody panel” result was highly sensitive, with high negative predictive value for CAM. The combination of these two approaches was 94% sensitive, detecting 15 of 16 CAM, with 100% sensitivity and negative predictive value in DM.Conclusions:These results may help clinicians predict which patients with myositis are at greater risk of developing cancer, thus identifying those requiring aggressive diagnostic evaluation and intensive cancer surveillance at myositis onset and follow-up.
This study aimed to identify the relationships between lower limb muscle characteristics and mechanical variables derived from the vertical (jumping) and horizontal (sprinting) force-velocity-power ...(FVP) profiles.
Nineteen subelite male rugby league players performed a series of squat jumps and linear 30-m sprints to derive the vertical and horizontal FVP profiles, respectively. The theoretical maximal force (F0), velocity (V0), and power (Pmax) were derived from both the vertical (i.e., vF0, vV0, and vPmax) and the horizontal (i.e., hF0, hV0, and hPmax) FVP profiles. Vastus lateralis (VL), biceps femoris long head, and gastrocnemius medialis (GM) and lateralis muscle fascicle length, pennation angle, and thickness were measured using B-mode ultrasonography. Magnetic resonance imaging was used to calculate volumes of major lower limb muscles, whereas proton magnetic resonance spectroscopy was used to quantify the carnosine content of the GM to estimate muscle fiber typology.
Variation in vPmax was best explained by GM muscle fiber typology (i.e., greater estimated proportion of Type II fibers) and VL volume (adjusted r2 = 0.440, P = 0.006), whereas adductor and vastus medialis volume and GM muscle fiber typology explained the most variation in hPmax (adjusted r2 = 0.634, P = 0.032). Rectus femoris and VL volume explained variation in vF0 (r2 = 0.430, P = 0.008), whereas adductor and vastus medialis volume explained variation in hF0 (r2 = 0.432, P = 0.007). Variations in vV0 and hV0 were best explained by GM muscle fiber typology (adjusted r2 = 0.580, P < 0.001) and GM muscle fiber typology and biceps femoris short head volume (adjusted r2 = 0.590, P < 0.001), respectively.
Muscle fiber typology and muscle volume are strong determinants of maximal muscle power in jumping and sprinting by influencing the velocity- and force-oriented mechanical variables.
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