Executive control in Parkinson's disease: effects of dopaminergic medication and deep brain stimulation on anti-cue keypress performance.

Using an anti-cue keypress task, we examined executive control in Parkinson's disease (PD) patients treated with deep brain stimulation (DBS) of the subthalamic nucleus (STN) and dopaminergic medication. Across sessions, we varied stimulation (on, off) and dopaminergic medication (on, off). Reaction time (RT) results of the PD patients and their age-matched controls showed a consistent pattern of RT costs and benefits generated by anti-cues with short and long preparation intervals, respectively.

Down-regulation of endogenes mediated by a transitive silencing signal.

Some RNA silencing systems in plants, nematodes, and fungi show spreading of silencing along target sequences, termed transitive silencing. Here, we address the question of whether endogenous targets can be silenced by a transitive silencing signal in plants. In transgenic Arabidopsis thaliana plants that harbored a silencing-inducing locus and a transgenic chimeric primary target, silencing of a secondary transgenic target occurred and the expression of the endogenous catalase genes was down-regulated, coinciding with a knock-down phenotype.

The frequency and efficiency of endogene suppression by transitive silencing signals is influenced by the length of sequence homology.

Transitivity, the spread of RNA silencing along primary target sequences, leads to the degradation of secondary targets that have no sequence homology to the initial silencing trigger. We demonstrate that increasing the distance between direct and adjacent target sequences in a transgenic primary target delays the onset of silencing of a secondary target gene. Silencing can spread in a 3' to 5' direction over a distance of at least 500 nucleotides (nt), but this requires consistently more time compared to a distance of 98 nt or 250 nt.

Introduction of silencing-inducing transgenes does not affect expression of known transcripts.

While the RNA interference (RNAi) mechanism has only been discovered a decade ago, RNAi is now often used to study gene function by sequence-specific knockdown of gene expression. However, it is still unknown whether introduction of silencing-inducing transgenes alters the transcriptome. To address this question, genome-wide transcriptional changes in silenced and non-silenced backgrounds were monitored through microarray analysis.

The trans-silencing capacity of invertedly repeated transgenes depends on their epigenetic state in tobacco.

We studied the in trans-silencing capacities of a transgene locus that carried the neomycin phosphotransferase II reporter gene linked to the 35S promoter in an inverted repeat (IR). This transgene locus was originally posttranscriptionally silenced but switched to a transcriptionally silenced epiallele after in vitro tissue culture. Here, we show that both epialleles were strongly methylated in the coding region and IR center.