Toxic effects of copper sulfate on the brains of term Hubbard broiler chicks: a stereological and biochemical study

Copper sulfate can cause different pathologies in different organ systems during development. We determined the effects of toxic levels of copper sulfate on brain development in term Hubbard broiler chicks using stereological and biochemical analyses. Hubbard broiler chicken eggs were divided into three groups: controls with no treatment, sham-treated animals and an experimental group. On day 1, 0.1 ml saline was injected into the air chambers of the sham and experimental groups. The experimental group received also 50 μg copper sulfate. At term (day 21), all chick brains were removed and their volumes were determined using the Cavalieri volume estimation. Parallel biochemical analyses were carried out for glutathione and malondialdehyde levels in the brain tissues as indicators of oxidative damage. With copper treatment, the mean brain volume (8079 μm³) was significantly decreased compared to both the control (10075 μm³) and sham (9547 μm³) groups. Copper treatment (143.8 nmol/g tissue) showed significantly decreased malondialdehyde levels compared to the control (293.6 nmol/g tissue) and sham groups (268.8 nmol/g tissue). Copper treatment (404.5 nmol/g tissue) showed significantly increased malondialdehyde levels compared to the control (158.6 nmol/g tissue) and sham (142.8 nmol/g tissue) groups. The morphological and biochemical parameters we measured demonstrated that in term Hubbard broiler chicks, toxic levels of copper sulfate cause developmental and oxidative brain damage.     

Different prion disease phenotypes result from inoculation of cattle with two temporally separated sources of sheep scrapie from Great Britain

Background

Given the theoretical proposal that bovine spongiform encephalopathy (BSE) could have originated from sheep scrapie, this study investigated the pathogenicity for cattle, by intracerebral (i.c.) inoculation, of two pools of scrapie agents sourced in Great Britain before and during the BSE epidemic. Two groups of ten cattle were each inoculated with pools of brain material from sheep scrapie cases collected prior to 1975 and after 1990. Control groups comprised five cattle inoculated with sheep brain free from scrapie, five cattle inoculated with saline, and for comparison with BSE, naturally infected cattle and cattle i.c. inoculated with BSE brainstem homogenate from a parallel study. Phenotypic characterisation of the disease forms transmitted to cattle was conducted by morphological, immunohistochemical, biochemical and biological methods.

Results

Disease occurred in 16 cattle, nine inoculated with the pre-1975 inoculum and seven inoculated with the post-1990 inoculum, with four cattle still alive at 83 months post challenge (as at June 2006). The different inocula produced predominantly two different disease phenotypes as determined by histopathological, immunohistochemical and Western immunoblotting methods and biological characterisation on transmission to mice, neither of which was identical to BSE. Whilst the disease presentation was uniform in all scrapie-affected cattle of the pre-1975 group, the post-1990 inoculum produced a more variable disease, with two animals sharing immunohistochemical and molecular profile characteristics with animals in the pre-1975 group.

Conclusion

The study has demonstrated that cattle inoculated with different pooled scrapie sources can develop different prion disease phenotypes, which were not consistent with the phenotype of BSE of cattle and whose isolates did not have the strain typing characteristics of the BSE agent on transmission to mice.     

The identification of informative genes from multiple datasets with increasing complexity

Background  

In microarray data analysis, factors such as data quality, biological variation, and the increasingly multi-layered nature of more complex biological systems complicates the modelling of regulatory networks that can represent and capture the interactions among genes. We believe that the use of multiple datasets derived from related biological systems leads to more robust models. Therefore, we developed a novel framework for modelling regulatory networks that involves training and evaluation on independent datasets. Our approach includes the following steps: (1) ordering the datasets based on their level of noise and informativeness; (2) selection of a Bayesian classifier with an appropriate level of complexity by evaluation of predictive performance on independent data sets; (3) comparing the different gene selections and the influence of increasing the model complexity; (4) functional analysis of the informative genes.     

B cell engagement with HIV-1 founder virus envelope predicts development of broadly neutralizing antibodies

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Effects of plasma- and cell-free perfusates on filtration coefficient of perfused canine lungs

The filtration coefficient (Kf,c) of the microvessels in isolated dog lungs were studied for whole and diluted blood, whole and diluted plasma, Tyrode's solution, and Tyrode's plus dextran (4%, 63,000 mol wt) perfusates. When whole blood and plasma were diluted, Kf,c increased abruptly at a plasma protein concentration between 4 and 5 g/l, an effect which was not dependent on the erythrocyte mass. Both Tyrode's and Tyrode's plus dextran produced increases in Kf,c (60 and 30%, respectively). The difference in Kf,c measured between these latter perfusates was completely abolished when Kf,c were corrected for viscosity differences. Thus the pulmonary microvasculature responds similarly to the systemic circulation in that complete removal of plasma proteins from the perfusate increases Kf,c by 50%. This effect is independent of erythrocyte mass or colloid osmotic pressure of the perfusate, since perfusion with dextran solutions alone also increased Kf,c.