Applications of the Premack Principle: A Review of the Literature.

The Premack principle states that any Response A can reinforce any other Response B if the independent rate of A is greater than the independent rate of B. This theory demonstrates reinforcer relativity, where the relative probabilities of responses can be more impactful than preference. Applying the Premack principle involves arranging the environment to restrict access to certain responses based on relative probabilities of a set of given responses. Though the Premack principle is described in modern behavior analytic texts, Konarski et al. identified a lack of empirical evidence to support its application. The purpose of the current paper is to systematically review the extant literature using the Premack principle and evaluate how and if researchers have applied reinforcer relativity as described by Premack and the subsequent effectiveness of these procedures. Additionally, we make recommendations for practitioners and future researchers based on our findings.

Augmentative and Alternative Communication and Speech Production for Individuals with ASD: A Systematic Review.

This review evaluated the effects of augmentative and alternative communication (AAC) on speech development in children with autism spectrum disorders (ASD); replicated, updated, and extended the systematic review by Schlosser and Wendt (American Journal of Speech-Language Pathology 17:212-230, 2008). Twenty-five single case design articles and three group design articles published between 1975 and May 2020 met inclusion criteria related to participant characteristics, intervention type, design, and visual analysis of dependent variable outcomes. Overall, AAC resulted in improved speech production; however, speech gains that did occur did not surpass AAC use.

cAMP signaling regulates histone H3 phosphorylation and mitotic entry through a disruption of G2 progression.

cAMP signaling is known to have significant effects on cell growth, either inhibitory or stimulatory depending on the cell type. Study of cAMP-induced growth inhibition in mammalian somatic cells has focused mainly on the combined role of protein kinase A (PKA) and mitogen-activated protein (MAP) kinases in regulation of progression through the G1 phase of the cell cycle. Here we show that cAMP signaling regulates histone H3 phosphorylation in a cell cycle-dependent fashion, increasing it in quiescent cells but dramatically reducing it in cycling cells. The latter is due to a rapid and dramatic loss of mitotic histone H3 phosphorylation caused by a disruption in G2 progression, as evidenced by the inhibition of mitotic entry and decreased activity of the CyclinB/Cdk1 kinase. The inhibition of G2 progression induced through cAMP signaling is dependent on expression of the catalytic subunit of PKA and is highly sensitive to intracellular cAMP concentration. The mechanism by which G2 progression is inhibited is independent of both DNA damage and MAP kinase signaling. Our results suggest that cAMP signaling activates a G2 checkpoint by a unique mechanism and provide new insight into normal cellular regulation of G2 progression.

Modulation of RNA polymerase assembly dynamics in transcriptional regulation.

The interaction of transcription factors with target genes is highly dynamic. Whether the dynamic nature of these interactions is merely an intrinsic property of transcription factors or serves a regulatory role is unknown. Here we have used single-cell fluorescence imaging combined with computational modeling and chromatin immunoprecipitation to analyze transcription complex dynamics in gene regulation during the cell cycle in living cells. We demonstrate a link between the dynamics of RNA polymerase I (RNA Pol I) assembly and transcriptional output. We show that transcriptional upregulation is accompanied by prolonged retention of RNA Pol I components at the promoter, resulting in longer promoter dwell time, and an increase in the steady-state population of assembling polymerase. As a consequence, polymerase assembly efficiency and, ultimately, the rate of entry into processive elongation are elevated. Our results show that regulation of rDNA transcription in vivo occurs via modulation of the efficiency of transcription complex subunit capture and assembly.

cAMP signaling induces rapid loss of histone H3 phosphorylation in mammary adenocarcinoma-derived cell lines.

The phosphorylation of histone H3 is known to play a role in regulation of transcription as well as preparation of chromosomes for mitosis. Various signaling cascades induce H3 phosphorylation, particularly at genes activated by these pathways. In this study, we show that signaling can also have the opposite effect. Activators of cAMP signaling induce a rapid and potent loss of H3 phosphorylation. This effect is not mediated through a cAMP metabolite since a membrane-permeable form of AMP had no effect on H3 phosphorylation and a phosphodiesterase-resistant cAMP analog efficiently reduced it. cAMP is also the likely regulator of H3 phosphorylation under physiological conditions since only supra-pharmacological doses of cGMP induce the loss of H3 phosphorylation. The loss of phosphorylation is specific for histone H3 since we do not observe drastic losses in total phosphorylation of other histones. In addition, other H3 modifications are unaffected with the exception of lysine 9 methylation, which is elevated. Analysis of cell growth and cell cycle shows that cAMP signaling inhibits cell growth and arrests cells at both G1 and G2/M. Similar effects of cAMP signaling on H3 phosphorylation are observed in a variety of mammary adenocarcinoma-derived cell lines. In syngeneic human breast-derived cell lines, one diploid and non-transformed, the other derived from a ductal carcinoma, the loss of H3 phosphorylation is significantly more sensitive to cAMP concentration in the transformed cell line.

Chromatin-dependent regulation of the MMTV promoter by cAMP signaling is mediated through distinct pathways.

The nucleoprotein structure of the mouse mammary tumor virus (MMTV) promoter defines its response to cAMP signaling. A stably replicating MMTV template in highly organized chromatin is repressed in the presence of cAMP, whereas a transiently transfected template with a disorganized structure is activated. In this study, we investigate the nature of the cAMP-induced signal(s) by which these opposing responses occur to gain insight into their mechanism. We demonstrate that the transcriptional changes observed at both templates are mediated through cAMP-dependent protein kinase A (PKA). In addition, the MMTV promoter lacks a consensus cAMP response element (CRE) and neither template requires cAMP response element-binding protein (CREB) to elicit a response to cAMP signaling. However, the responses of the two templates differ mechanistically in that the CREB-binding protein p300 potentiates activation from the transient template in a manner dependent on its Cys/His-rich region 3, but does not appear to affect the repression of the replicating chromatin template. Chromatin immunoprecipitation assays show that cAMP treatment results in a decrease in acetylation of histone H4, and in multiple modifications of histone H3 at specific nucleosomes in the promoter region of the stable MMTV template. These findings suggest novel CREB-independent, chromatin-dependent pathways for transcriptional regulation by cAMP.

Quantitation of calcitonin gene-related peptide mRNA and neuronal cell death in facial motor nuclei following axotomy and 633 nm low power laser treatment.

BACKGROUND AND OBJECTIVES: A persistent increase in calcitonin gene-related peptide (CGRP) immunoreactivity in motoneurons may serve as an indicator for regeneration after peripheral nerve injury [Borke et al., J Neurocytol 1993;22:141-153]. STUDY DESIGN/MATERIALS AND METHODS: We examined the effects of low power laser treatment (633 nm) on axotomy-induced changes in alpha-CGRP mRNA and long-term neuronal survival in facial motoneurons. A quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) assay for alpha-CGRP mRNA was used to detect changes in the response to axotomy and laser irradiation. Cell counts of neurons in injured and non-injured facial motor nuclei of laser-treated and non-treated rats were done to estimate neuronal survival. RESULTS: A 10-fold increase (P < 0.0001) in mRNA for alpha-CGRP at 11 days post-transection and an almost threefold increase (P < 0.0001) in neuronal survival at 6-9 months post-transection were found in 633 nm light treated rats. DISCUSSION: These findings demonstrate that 633 nm laser light upregulates CGRP mRNA and support the theory that laser irradiation increases the rate of regeneration, target reinnervation, and neuronal survival of the axotomized neuron.