The effect of dietary aflatoxin on wild turkey poults

Aflatoxins, toxic metabolites of Aspergillus flavus or Aspergillus parasiticus, cause poor feed utilization, decreased weight gains, depressed immune function, liver dysfunction, coagulation abnormalities, and death in a wide variety of species including humans. Conservationists have become concerned that increasingly popular wildlife feeding or baiting practices could expose wildlife to toxic amounts of aflatoxin-contaminated grains. In particular, the effects of aflatoxins on the wild turkey (Meleagris gallopova silvestris) are of concern because the conspecific domestic turkey is highly susceptible to aflatoxins. To evaluate the effect of dietary aflatoxin on wild turkeys, four groups of 4-mo-old wild turkeys were fed diets containing either 0, 100, 200, or 400 micrograms aflatoxin/kg feed for 2 wk in September and October 1996. Aflatoxin-fed poults had decreased feed consumption and weight gains as compared with control poults. Decreased liver-to-body weight ratios, liver enzyme alterations, slightly altered blood coagulation patterns, and mild histologic changes indicated low-level liver damage. Compromise of cell-mediated immunity was indicated by decreased lymphoblast transformation. The effects were apparent in all treatment groups to variable levels, but significant differences most often were found at 400 micrograms aflatoxin/kg feed. This study shows that short-term aflatoxin ingestion by wild turkeys can induce undesirable physiologic changes; therefore, exposure of wild turkeys to feeds containing aflatoxin levels of 100 micrograms aflatoxin/kg feed or more should be avoided.     

Identification of sequence motifs in oligonucleotides whose presence is correlated with antisense activity

Design of antisense oligonucleotides targeting any mRNA can be much more efficient when several activity-enhancing motifs are included and activity-decreasing motifs are avoided. This conclusion was made after statistical analysis of data collected from >1000 experiments with phosphorothioate-modified oligonucleotides. Highly significant positive correlation between the presence of motifs CCAC, TCCC, ACTC, GCCA and CTCT in the oligonucleotide and its antisense efficiency was demonstrated. In addition, negative correlation was revealed for the motifs GGGG, ACTG, AAA and TAA. It was found that the likelihood of activity of an oligonucleotide against a desired mRNA target is sequence motif content dependent.     

Acetaldehyde-stimulated PKC activity in airway epithelial cells treated with smoke extract from normal and smokeless cigarettes

Previously, we have found that acetaldehyde, a volatile component of cigarette smoke, stimulates the protein kinase C (PKC) pathway and inhibits ciliary motility. A "smokeless" cigarette (Eclipse) now exists in which most of the tobacco is not burned, reducing the pyrolyzed components in the extract. We hypothesized that acetaldehyde is a component of cigarette smoke that activates PKC in the airway epithelial cell, and therefore the Eclipse cigarette would not activate epithelial cell PKC. In this study, bovine bronchial epithelial cells (BBEC) were incubated with cigarette smoke extract (CSE) or Eclipse smoke extract (ESE). We found that PKC activity was significantly higher in cells exposed to 5% CSE than cells exposed to 5% ESE or media. When acetaldehyde levels of both extracts were measured by gas chromatography, CSE was found to have 15-20 times greater concentration (microM) of acetaldehyde than ESE. When BBEC were treated with 5% CSE, ciliary beating was further decreased from baseline levels. This decrease in ciliary beating was not observed in cells treated with ESE, suggesting that acetaldehyde contained in CSE slows cilia. These results suggest that volatile components such as acetaldehyde in cigarette smoke may inhibit ciliary motility via a PKC-dependent mechanism.     

Simulated brain tumor growth dynamics using a three-dimensional cellular automaton

We have developed a novel and versatile three-dimensional cellular automaton model of brain tumor growth. We show that macroscopic tumor behavior can be realistically modeled using microscopic parameters. Using only four parameters, this model simulates Gompertzian growth for a tumor growing over nearly three orders of magnitude in radius. It also predicts the composition and dynamics of the tumor at selected time points in agreement with medical literature. We also demonstrate the flexibility of the model by showing the emergence, and eventual dominance, of a second tumor clone with a different genotype. The model incorporates several important and novel features, both in the rules governing the model and in the underlying structure of the model. Among these are a new definition of how to model proliferative and non-proliferative cells, an isotropic lattice, and an adaptive grid lattice.