Proteomic Analysis of Tendon Extracellular Matrix Reveals Disease Stage- specific Fragmentation and Differential Cleavage of COMP ( Cartilage Oligomeric Matrix Protein)

During inflammatory processes the extracellular matrix (ECM) is extensively remodeled, and many of the constituent components are released as proteolytically cleaved fragments. These degradative processes are better documented for inflammatory joint diseases than tendinopathy even though the pathogenesis has many similarities. The aims of this study were to investigate the proteomic composition of injured tendons during early and late disease stages to identify disease-specific cleavage patterns of the ECM protein cartilage oligomeric matrix protein (COMP). In addition to characterizing fragments released in naturally occurring disease, we hypothesized that stimulation of tendon explants with proinflammatory mediators in vitro would induce fragments of COMP analogous to natural disease. Therefore, normal tendon explants were stimulated with IL-1β and prostaglandin E2, and their effects on the release of COMP and its cleavage patterns were characterized. Analyses of injured tendons identified an altered proteomic composition of the ECM at all stages post injury, showing protein fragments that were specific to disease stage. IL-1β enhanced the proteolytic cleavage and release of COMP from tendon explants, whereas PGE2 had no catabolic effect. Of the cleavage fragments identified in early stage tendon disease, two fragments were generated by an IL-1-mediated mechanism. These fragments provide a platform for the development of neo-epitope assays specific to injury stage for tendon disease

Parameter inference in mechanistic models of cellular regulation and signalling pathways using gradient matching

A challenging problem in systems biology is parameter inference in mechanistic models of signalling pathways. In the present article, we investigate an approach based on gradient matching and nonparametric Bayesian modelling with Gaussian processes. We evaluate the method on two biological systems, related to the regulation of PIF4/5 in Arabidopsis thaliana, and the JAK/STAT signal transduction pathway

Time-dependent models of dense PDRs with complex molecules

We present a study of the chemistry of a dense photon-dominated region (PDR) using a time-dependent chemical model. Our major interest is to study the spatial distribution of complex molecules such as hydrocarbons and cyanopolyynes in the cool dense material bordering regions where star formation has taken place. Our standard model uses a homogeneous cloud of density 2x10e4 cm-3 and temperature T=40 K, which is irradiated by a far-ultraviolet radiation field of intermediate intensity, given by X=100. We find that over a range of times unsaturated hydrocarbons (e.g., C2H, C4H, C3H2) have relatively high fractional abundances in the more external layers of the PDR, whereas their abundances in the innermost layers are several orders of magnitudes lower. On the other hand, molecules that are typical of late-time chemistry are usually more abundant in the inner parts of the PDR. We also present results for models with different density, temperature, intensity of the radiation field and initial fractional abundances. Our results are compared with both high- and moderate-angular resolution observations of the Horsehead nebula. Our standard model is partially successful in reproducing the observations. Additional models run with different physical parameters are able to reproduce the abundance of many of the observed molecules, but we do not find a single model that fits all the observations at the same time. We discuss the suitability of a time-dependent model of a dense PDR such as ours as an estimator of the age of a PDR, provided that enough observational data exist.Comment: 15 pages, 12 figures, 8 tables, to be published in MNRA

Regulation of vascular endothelial growth factor bioactivity in patients with acute lung injury

Background: Reduced bioactive vascular endothelial growth factor (VEGF) has been demonstrated in several inflammatory lung conditions including the acute respiratory distress syndrome (ARDS). sVEGFR-1, a soluble form of VEGF-1 receptor, is a potent natural inhibitor of VEGF. We hypothesised that sVEGFR-1 plays an important role in the regulation of the bioactivity of VEGF within the lung in patients with ARDS. Methods: Forty one patients with ARDS, 12 at risk of developing ARDS, and 16 normal controls were studied. Bioactive VEGF, total VEGF, and sVEGFR-1 were measured by ELISA in plasma and bronchoalveolar lavage (BAL) fluid. Reverse transcriptase polymerase chain reaction for sVEGFR-1 was performed on BAL cells. Results: sVEGFR-1 was detectable in the BAL fluid of 48% (20/41) of patients with early ARDS (1.4– 54.8 ng/ml epithelial lining fluid (ELF)) compared with 8% (1/12) at risk patients (p = 0.017) and none of the normal controls (p = 0.002). By day 4 sVEGFR-1 was detectable in only 2/18 ARDS patients (p = 0.008). Patients with detectable sVEGFR-1 had lower ELF median (IQR) levels of bioactive VEGF than those without detectable sVEGFR-1 (1415.2 (474.9–3192) pg/ml v 4761 (1349–7596.6) pg/ml, median difference 3346 pg/ml (95% CI 305.1 to 14711.9), p = 0.016), but there was no difference in total VEGF levels. BAL cells expressed mRNA for sVEGFR-1 and produced sVEGFR-1 protein which increased following incubation with tumour necrosis factor a. Conclusion: This study shows for the first time the presence of sVEGFR-1 in the BAL fluid of patients with ARDS. This may explain the presence of reduced bioactive VEGF in patients early in the course of ARDS

The Effect of Carbon Dioxide on Nitrate Accumulation in Carrington Loam

Most microorganisms obtain carbon as well as energy from the oxidation of organic compounds but the nitrifying bacteria assimilate carbon dioxide from the air as a source of carbon. The sulfur bacteria and the hydrogen oxidizing bacteria also assimilate carbon dioxide from the air. Other bacteria that cannot assimilate carbon dioxide from the air are greatly stimulated by its presence. Increasing the concentration of carbon dioxide in the air about cultures of Lactobacillus acidophilus produces higher plate counts and larger colonies than cultures in carbon dioxide-free air. An increased concentration of carbon dioxide in the soil air stimulates the growth of certain of the fungi, particularly those associated with root-rot of the higher plants. Some of the fleshy fungi, the so-called lignin-destroying fungi, are greatly retarded in growth by the removal of carbon dioxide from the atmosphere in which they grow. On the other hand, there are cases on record in which carbon dioxide has acted as a growth depressant or germicide. The spores of Mucor, Aspergillus and Penicillium are prevented from germination by very high concentrations of carbon dioxide. The growth rate of yeast and fermentation of solutions have been retarded by certain concentrations of carbon dioxide

A Method for Determining the Exchange Capacity of Organic Matter in the Presence of Nitrogen and Calcium

Many methods have been used for determining the base exchange capacity of soils and certain advantages have been claimed by each investigator for his particular method. Fewer studies on the base exchange reactions of organic matter have been made and the nature of the material makes many of the methods used for soils impracticable and inaccurate when applied to organic matter. According to McGeorge (1) the monovalent lignin salts are soluble in alcohol and the use of alcohol in base exchange studies on organic matter is of questionable value. The removal of excess soluble salt from the base exchange complex preparatory to determining the amount of base fixed, by the use of water, allows too great a hydrolysis of monovalent salts and, therefore, will lead to low results. Then again, the monovalent lignin salts are soluble under certain conditions in salt solution, and especially in acetate solutions which hydrolyze and yield OH ions

The Effect of Carbon Dioxide on the Yield, Phosphorus and Calcium Contents of Wheat

The concentration of carbon dioxide in the atmosphere is normally about 0.03 per cent but the soil atmosphere usually contains considerably more than this amount especially in the vicinity of roots of rapidly growing plants. The carbon dioxide produced by the plant roots and by microbiological action diffuses from the soil and increases the concentration of carbon dioxide in the atmosphere immediately surrounding the above-ground portions of the plant. It is this carbon dioxide from the soil which the plant utilizes in its growth and hence the significance of an adequate supply is at once apparent. The influence of carbon dioxide on plant growth and on bacterial action in the soil and its effect on the availability of phosphorus and potassium have been studied to some extent but the problem as a whole is far from solved as yet

The Relative Solubility of Soil Phosphorus in Different Solvents

Various investigators have shown that carbon dioxide is important in the soil in making the plant food elements available. As a result attempts have been made to use solvents which are similar to carbon dioxide in their solubility effects on soil phosphorus. In many cases, the available phosphorus as measured by these solvents has correlated rather well with crop responses to phosphate fertilizer in the field, but the correlation is not perfect in all soils

Cloth & memory

This book was published to accompany an exhibition of the same name at Salts Mills, Saltaire, Yorkshire, UK, in summer 2012, conceived and directed by Lesley Millar MBE, Professor of Textile Culture at the University for the Creative Arts. The exhibition and accompanying publication includes work by the artists Beverley Ayling-Smith, Carol Quarini, and Bob White. All visited Salts Mills and Saltaire and have created their work as a response to the history of the place: the memory of cloth and the making of cloth that has seeped into the fabric of the building. This exhibition is the first of two; Cloth and Memory 2 taking place in 2013