Avian Health across the Landscape: Nestling Immunity Covaries with Changing Landcover.

The landscape composition of an organism's home range or territory should influence aspects of its condition, including measures of immune function. Changes in immunocompetence arising from variation in landcover may provide important links between habitat changes and patterns of disease spread. To establish a baseline understanding for whether immune measures covary with changes in landcover, we examined associations between immunological parameters and landcover composition for adults and nestlings of five shrubland bird species. Specifically, we examined the bacteria-killing ability (BKA) of the blood plasma and profiles of the five avian leukocytes as our measures of immune function, and assessed the proportion of area around each bird's nest that was composed of the four major landcover types in the Midwestern USA: row crop agriculture, developed, forest, and grass/shrub. We performed landcover assessments at 100 and 1000 m radius buffers to identify whether associations between habitat and immune function differed at the two spatial scales. As part of this work, we examined age and species-related immunological variation, as well as associations among the immune parameters. There was little evidence linking variation in immune function to landcover composition for the adults at either spatial scale, but there were numerous associations for nestlings, and these were stronger at the 1000 than 100 m spatial scale. The proportion of grass/shrub around the nest had the largest impact on immune function, although the effect varied by immune parameter and species. BKA and basophils were inversely associated with grass/shrub for all species, whereas lymphocytes were positively associated with grass/shrub for all species. We also documented species-level differences among adults and nestlings for BKA and all leukocytes except monocytes. As expected, we found that nestlings had reduced levels of BKA, lymphocytes, monocytes, and elevated heterophils compared with adults (except for field sparrow-Spizella pusilla-nestlings, which had higher lymphocytes). Basophils generally did not differ by age class, and eosinophils exhibited species-specific patterns, in which they were higher for nestling American robins (Turdus migratorius) and gray catbirds (Dumetella carolinensis) compared with adults, but lower in the other nestlings. Heterophils and lymphocytes were inversely associated for all species and age classes, and basophil levels were positively associated with BKA across species and age classes. Together, these findings bolster our understanding of age and species-specific variation in immune function, and provide evidence that immune measures can covary with changes in landcover.

Assessment of wall shear stress in arteries, applied to the coronary circulation.

Time dependent wall shear rates cannot be directly or accurately measured in arteries using presently available techniques. Here a simple method is presented for calculating them from a single measured velocity waveform (either centreline or cross-sectionally averaged velocity). The method involves only Fourier analysis and the application of given formulae, and it is expected to be approximately valid in any segment of artery which has no branches or sharp curves for a distance of several diameters. It is shown, however, that a frequency response of 30 Hz is required in the velocity measuring device if the resulting wall shear rate waveform is to be accurate throughout the cycle although 10 Hz is adequate if only the rms value is desired. This restriction on accuracy applies to this or any other method of estimating time-dependent wall shear. The method is applied to a prediction of wall shear in the left coronary arteries of the horse, based on measured velocities where they are available and calculated ones where they are not; the results show that in vivo the amplitude of wall shear fluctuations is much greater than the mean. The method is also applied to a scaled down model of the horse coronaries, thought to be representative of man; here the unsteadiness is still important but no longer dominant. The variation of wall shear with distance along the artery is discussed in the context of atherogenesis.

Classification of disability and distress by ward nurses: a reliability study.

In a series of trials, ward nurses independently classified the disability and distress states of medical and surgical patients. Criteria for inter-rater reliability, in terms of correlation and absence of bias, were met after each rater had taken part in a training session which gave immediate feedback about performance.

Rationally designed selective inhibitors of trypanothione reductase. Phenothiazines and related tricyclics as lead structures.

Trypanothione reductase, an essential component of the anti-oxidant defences of parasitic trypanosomes and Leishmania, differs markedly from the equivalent host enzyme, glutathione reductase, in the binding site for the disulphide substrate. Molecular modelling of this region suggested that certain tricyclic compounds might bind selectively to trypanothione reductase without inhibiting host glutathione reductase. This was confirmed by testing 30 phenothiazine and tricyclic antidepressants, of which clomipramine was found to be the most potent, with a K(i) of 6 microM, competitive with respect to trypanothione. Many of these compounds have been noted previously to have anti-trypanosomal and anti-leishmanial activity and thus they can serve as lead structures for rational drug design.

Rational design of peptide-based inhibitors of trypanothione reductase as potential antitrypanosomal drugs.

The rational design of ligands for the substrate-binding site of a homology-modelled trypanothione reductase (TR) was performed. Peptides were designed to be selective for TR over human glutathione reductase (GR). The design process capitalized on the proposed differences between the activesites of TR and human GR, subsequently confirmed by the TR crystal structure. Enzyme kinetics confirmed that forT. cruzi TR benzoyl-Leu-Arg-Arg-ß-naphthylamide was an inhibitor (Ki 13.8µM) linearly competitive with the native substrate, trypanothione disulphide, and did not inhibit glutathione reductase.