Rapid modification of the glycocalyx caused by ischemia-reperfusion is inhibited by adenosine A2A receptor activation

Ischemia-reperfusion (I/R) has been shown to cause microvascular dysfunction and to alter the appearance of the glycocalyx in electron micrographs. We hypothesized that I/R injury might alter the structure and/or permeability of the glycocalyx. Prior work had shown a role for adenosine in protection from I/R injury, and, therefore, we also explored the idea that activation of the adenosine A(2A) receptor would attenuate I/R glycocalyx injury. Here, we report that I/R causes a rapid and dramatic decrease in the ability of the glycocalyx to exclude FITC-Dextran 70 (Dex70). Over a reperfusion period of 45 min, the glycocalyx dye exclusion zone for Dex70 decreased by one-half in capillaries and postcapillary venules, whereas the red blood cell exclusion zone was very slightly reduced in capillaries only. Pretreatment with the A(2A) agonist ATL-146e significantly inhibited the changes in both vessel types. The modifications of the glycocalyx appear to be an early step in the inflammatory cascade typically associated with reperfusion injury, and adenosine A(2A) receptor activation may play a role in protection from this injury.     

Biopharmaceutical liquid formulation: a review of the science of protein stability and solubility in aqueous environments

Formulation scientists employed in the biopharmaceutical industry face the challenge of creating liquid aqueous formulations for proteins that never had evolutionary pressure to be exceptionally stable or soluble. Yet commercial products usually need a shelf life of 2 years to be economically viable. The research done in this field is dominated by physical chemists who have developed theories like preferential interaction, preferential hydration and excluded volume to explain the mechanisms for the interaction between salt, small organic molecules and proteins. This review aims to translate the research findings on protein stability and solubility produced by the physical chemists and make it accessible to formulation scientists working within the biopharmaceutical industry.     

The Association of Blood Groups and Certain Eye Diseases

The blood of patients suffering from cataracts, glaucoma and strabismus was grouped and the distribution of their blood groups was compared with that of blood groups in volunteers at blood donor clinics. It was found that there was no significant difference between the distribution of groups among these patients and that among the controls.     

Long-term haemodialysis and thyroid function.

Several indices of thyroid function were assessed in 74 patients with chronic renal failure. Sixty patients had undergone haemodialysis for varying periods. Within the first six months of haemodialysis treatment protein-bound iodine and total thyroxine (T4) levels rose, but after this T4 levels and the free thyroxine index fell progressively. Three out of the 12 patients who had undergone haemodialysis for longer than three years had subnormal T4 and supranormal thyrotrophin concentrations and a subnormal response to thyrotrophin stimulation. Lon-term haemodialysis may be a cause of biochemical hypothyroidism.     

Interactions between Canopy Structure and Herbaceous Biomass along Environmental Gradients in Moist Forest and Dry Miombo Woodland of Tanzania

We have limited understanding of how tropical canopy foliage varies along environmental gradients, and how this may in turn affect forest processes and functions. Here, we analyse the relationships between canopy leaf area index (LAI) and above ground herbaceous biomass (AGB_H) along environmental gradients in a moist forest and miombo woodland in Tanzania. We recorded canopy structure and herbaceous biomass in 100 permanent vegetation plots (20 m × 40 m), stratified by elevation. We quantified tree species richness, evenness, Shannon diversity and predominant height as measures of structural variability, and disturbance (tree stumps), soil nutrients and elevation as indicators of environmental variability. Moist forest and miombo woodland differed substantially with respect to nearly all variables tested. Both structural and environmental variables were found to affect LAI and AGB_H, the latter being additionally dependent on LAI in moist forest but not in miombo, where other factors are limiting. Combining structural and environmental predictors yielded the most powerful models. In moist forest, they explained 76% and 25% of deviance in LAI and AGB_H, respectively. In miombo woodland, they explained 82% and 45% of deviance in LAI and AGB_H. In moist forest, LAI increased non-linearly with predominant height and linearly with tree richness, and decreased with soil nitrogen except under high disturbance. Miombo woodland LAI increased linearly with stem density, soil phosphorous and nitrogen, and decreased linearly with tree species evenness. AGB_H in moist forest decreased with LAI at lower elevations whilst increasing slightly at higher elevations. AGB_H in miombo woodland increased linearly with soil nitrogen and soil pH. Overall, moist forest plots had denser canopies and lower AGB_H compared with miombo plots. Further field studies are encouraged, to disentangle the direct influence of LAI on AGB_H from complex interrelationships between stand structure, environmental gradients and disturbance in African forests and woodlands.     

Understanding the structural and dynamic consequences of DNA epigenetic modifications: Computational insights into cytosine methylation and hydroxymethylation

We report a series of molecular dynamics (MD) simulations of up to a microsecond combined simulation time designed to probe epigenetically modified DNA sequences. More specifically, by monitoring the effects of methylation and hydroxymethylation of cytosine in different DNA sequences, we show, for the first time, that DNA epigenetic modifications change the molecule''s dynamical landscape, increasing the propensity of DNA toward different values of twist and/or roll/tilt angles (in relation to the unmodified DNA) at the modification sites. Moreover, both the extent and position of different modifications have significant effects on the amount of structural variation observed. We propose that these conformational differences, which are dependent on the sequence environment, can provide specificity for protein binding.