Tempo and Mode in Evolution of Transcriptional Regulation

Perennial questions of evolutionary biology can be applied to gene regulatory systems using the abundance of experimental data addressing gene regulation in a comparative context. What is the tempo (frequency, rate) and mode (way, mechanism) of transcriptional regulatory evolution? Here we synthesize the results of 230 experiments performed on insects and nematodes in which regulatory DNA from one species was used to drive gene expression in another species. General principles of regulatory evolution emerge. Gene regulatory evolution is widespread and accumulates with genetic divergence in both insects and nematodes. Divergence in cis is more common than divergence in trans. Coevolution between cis and trans shows a particular increase over greater evolutionary timespans, especially in sex-specific gene regulation. Despite these generalities, the evolution of gene regulation is gene- and taxon-specific. The congruence of these conclusions with evidence from other types of experiments suggests that general principles are discoverable, and a unified view of the tempo and mode of regulatory evolution may be achievable

Meeting report: moving upstream-evaluating adverse upstream end points for improved risk assessment and decision-making.

BackgroundAssessing adverse effects from environmental chemical exposure is integral to public health policies. Toxicology assays identifying early biological changes from chemical exposure are increasing our ability to evaluate links between early biological disturbances and subsequent overt downstream effects. A workshop was held to consider how the resulting data inform consideration of an "adverse effect" in the context of hazard identification and risk assessment.ObjectivesOur objective here is to review what is known about the relationships between chemical exposure, early biological effects (upstream events), and later overt effects (downstream events) through three case studies (thyroid hormone disruption, antiandrogen effects, immune system disruption) and to consider how to evaluate hazard and risk when early biological effect data are available.DiscussionEach case study presents data on the toxicity pathways linking early biological perturbations with downstream overt effects. Case studies also emphasize several factors that can influence risk of overt disease as a result from early biological perturbations, including background chemical exposures, underlying individual biological processes, and disease susceptibility. Certain effects resulting from exposure during periods of sensitivity may be irreversible. A chemical can act through multiple modes of action, resulting in similar or different overt effects.ConclusionsFor certain classes of early perturbations, sufficient information on the disease process is known, so hazard and quantitative risk assessment can proceed using information on upstream biological perturbations. Upstream data will support improved approaches for considering developmental stage, background exposures, disease status, and other factors important to assessing hazard and risk for the whole population

Dendropanax morbifera Léveille extract ameliorates cadmium-induced impairment in memory and hippocampal neurogenesis in rats

BACKGROUND: Cadmium leads to learning and memory impairment. Dendropanax morbifera Léveille stem extract (DMS) reduces cadmium-induced oxidative stress in the hippocampus. We investigated the effects of DMS on cadmium-induced impairments in memory in rats. METHODS: Cadmium (2 mg/kg), with or without DMS (100 mg/kg), was orally administered to 7-week-old Sprague-Dawley rats for 28 days. Galantamine (5 mg/kg), an acetylcholinesterase inhibitor, was intraperitoneally administered as a positive control. A novel-object recognition test was conducted 2 h after the final administration. Cell proliferation and neuroblast differentiation were assessed by immunohistochemistry for Ki67 and doublecortin, respectively. Acetylcholinesterase activity in the synaptosomes of the hippocampus was also measured based on the formation of 5,5′-dithio-bis-acid nitrobenzoic acid. RESULTS: An increase in the preferential exploration time of new objects was observed in both vehicle-treated and cadmium-treated rats. In addition, DMS administration increased cell proliferation and neuroblast differentiation in the dentate gyrus of vehicle-treated and cadmium-treated rats. Acetylcholinesterase activity in the hippocampal synaptosomes was also significantly higher in the DMS-treated group than in the vehicle-treated group. The effect of DMS on cadmium-induced memory impairment and cell proliferation in the hippocampus was comparable to that of galantamine. CONCLUSIONS: These results suggest that DMS ameliorates cadmium-induced memory impairment via increase in cell proliferation, neuroblast differentiation, and acetylcholinesterase activity in the hippocampus. The consumption of DMS may reduce cadmium-induced neurotoxicity in animals or humans