Some reflections on 25 years of the association for behavior analysis: Past, present, and future.

This paper offers some reflections on the discipline and profession of behavior analysis, as well as on the Association for Behavior Analysis (ABA), on the occasion of the association's 25th anniversary. It is based on a panel session conducted at the 1999 convention that included six past presidents of ABA (Donald M. Baer, Judith E. Favell, Sigrid S. Glenn, Philip N. Hineline, Jack Michael, and Edward K. Morris) and its current Executive Director and Secretary-Treasurer (Maria E. Malott). Among the topics addressed were (a) the survival of behavior analysis in university and cultural contexts, (b) the training of behavior-analytic researchers and practitioners, (c) relations between basic and applied research, (d) convergences between behavior analysis and other disciplines, (e) the structure and function of ABA, and (f) the importance of students for the future of the association, the discipline, and the profession. Questions from the audience raised issues concerning the relevance of major behavior-analytic journals, advances in behavior analysis since the death of B. F. Skinner, and the availability of accessible, popular material on applied behavior analysis.

DNA methylation at mammalian replication origins.

In Escherichia coli, DNA methylation regulates both origin usage and the time required to reassemble prereplication complexes at replication origins. In mammals, at least three replication origins are associated with a high density cluster of methylated CpG dinucleotides, and others whose methylation status has not yet been characterized have the potential to exhibit a similar DNA methylation pattern. One of these origins is found within the approximately 2-kilobase pair region upstream of the human c-myc gene that contains 86 CpGs. Application of the bisulfite method for detecting 5-methylcytosines at specific DNA sequences revealed that this region was not methylated in either total genomic DNA or newly synthesized DNA. Therefore, DNA methylation is not a universal component of mammalian replication origins. To determine whether or not DNA methylation plays a role in regulating the activity of origins that are methylated, the rate of remethylation and the effect of hypomethylation were determined at origin beta (ori-beta), downstream of the hamster DHFR gene. Remethylation at ori-beta did not begin until approximately 500 base pairs of DNA was synthesized, but it was then completed by the time that 4 kilobase pairs of DNA was synthesized (<3 min after release into S phase). Thus, DNA methylation cannot play a significant role in regulating reassembly of prereplication complexes in mammalian cells, as it does in E. coli. To determine whether or not DNA methylation plays any role in origin activity, hypomethylated hamster cells were examined for ori-beta activity. Cells that were >50% reduced in methylation at ori-beta no longer selectively activated ori-beta. Therefore, at some loci, DNA methylation either directly or indirectly determines where replication begins.

Activity of the c-myc replicator at an ectopic chromosomal location.

DNA replication starts at multiple discrete sites across the human chromosomal c-myc region, including two or more sites within 2.4 kb upstream of the c-myc gene. The corresponding 2.4-kb c-myc origin fragment confers autonomously replicating sequence (ARS) activity on plasmids, which specifically initiate replication in the origin fragment in vitro and in vivo. To test whether the region that displays plasmid replicator activity also acts as a chromosomal replicator, HeLa cell sublines that each contain a single copy of the Saccharomyces cerevisiae FLP recombinase target (FRT) sequence flanked by selectable markers were constructed. A clonal line containing a single unrearranged copy of the transduced c-myc origin was produced by cotransfecting a donor plasmid containing the 2.4-kb c-myc origin fragment and FRT, along with a plasmid expressing the yeast FLP recombinase, into cells containing a chromosomal FRT acceptor site. The amount of short nascent DNA strands at the chromosomal acceptor site was quantitated before and after targeted integration of the origin fragment. Competitive PCR quantitation showed that the c-myc origin construct substantially increased the amount of nascent DNA relative to that at the unoccupied acceptor site and to that after the insertion of non-myc DNA. The abundance of nascent strands was greatest close to the c-myc insert of the integrated donor plasmid, and significant increases in nascent strand abundance were observed at sites flanking the insertion. These results provide biochemical and genetic evidence for the existence of chromosomal replicators in metazoan cells and are consistent with the presence of chromosomal replicator activity in the 2.4-kb region of c-myc origin DNA.

Response rate, latency, and resistance to change.

Pigeons were trained on a multiple variable-interval/variable-interval schedule with pacing contingencies that generated high response rates in one component and low response rates in the other. Timeout periods separated the schedule components. During resistance-to-change tests, response-independent food was presented during the timeout periods, and the duration of that food presentation was varied among test sessions. Response rates in the schedule components decreased and latencies to the first response increased as a function of the duration of food presentations during the timeout. Both dependent measures changed about the same amount relative to their own baseline levels. The conclusions are that baseline response rates controlled by pacing contingencies are equally resistant to change, given equal reinforcement densities, and latency is a sensitive measure of resistance to change.