Levoamphetamine and Dextroamphetamine: Differential Effect on Aggression and Hyperkinesis in Children and Dogs

In laboratory experiments with hyperkinetic, untrainable dogs and in a comparison of levoamphetamine, dextroamphetamine, and placebo in children, levoamphetamine and dextroamphetamine were found to be approximately equal in calming an aggressive, hostile dog and in benefiting "unsocialized-aggressive" children; dextroamphetamine was more effective than levoamphetamine in calming "nervousness" and hyperactivity in dogs and in overanxious-hyperkinetic children. These data suggest that in the hyperkinetic syndrome, aggression and hostility may be benefited equally by levoamphetamine or dextroamphetamine via a dopaminergic mechanism, while anxiety and overactivity may be benefited significantly only by the dextro isomer via a norepinephrinergic mechanism

Location analysis for the estrogen receptor-α reveals binding to diverse ERE sequences and widespread binding within repetitive DNA elements

Location analysis for estrogen receptor-α (ERα)-bound cis-regulatory elements was determined in MCF7 cells using chromatin immunoprecipitation (ChIP)-on-chip. Here, we present the estrogen response element (ERE) sequences that were identified at ERα-bound loci and quantify the incidence of ERE sequences under two stringencies of detection: <10% and 10–20% nucleotide deviation from the canonical ERE sequence. We demonstrate that ∼50% of all ERα-bound loci do not have a discernable ERE and show that most ERα-bound EREs are not perfect consensus EREs. Approximately one-third of all ERα-bound ERE sequences reside within repetitive DNA sequences, most commonly of the AluS family. In addition, the 3-bp spacer between the inverted ERE half-sites, rather than being random nucleotides, is C(A/T)G-enriched at bona fide receptor targets. Diverse ERα-bound loci were validated using electrophoretic mobility shift assay and ChIP-polymerase chain reaction (PCR). The functional significance of receptor-bound loci was demonstrated using luciferase reporter assays which proved that repetitive element ERE sequences contribute to enhancer function. ChIP-PCR demonstrated estrogen-dependent recruitment of the coactivator SRC3 to these loci in vivo. Our data demonstrate that ERα binds to widely variant EREs with less sequence specificity than had previously been suspected and that binding at repetitive and nonrepetitive genomic targets is favored by specific trinucleotide spacers