Constant time delay to teach reading to students with intellectual disability and autism: a review.

The ability to read promotes academic success and serves as an essential prerequisite skill for many postsecondary opportunities. However, developing proficient reading skills is particularly difficult for many individuals with intellectual disability (ID) and autism spectrum disorder (ASD). Reading is an important life skill for all individuals, and it is essential for reading instruction to be grounded in research to achieve optimal learning outcomes. We conducted a review of the literature covering a 15-year period (2005-2020) to examine research measuring the effects of an evidence-based practice, constant time delay (CTD), when used as a reading intervention to teach participants with ID and/or ASD. Studies evaluated the acquisition of functional or academic reading skills across two instructional delivery methods: teacher-delivered and technology-based CTD. All reviewed research used a single case research design to experimentally validate the effects of CTD as a reading intervention, and findings across studies revealed a functional relationship between variables. That is, when applied as a reading intervention, CTD led to acquisition of academic or functional reading skills in participants with ID and/or ASD regardless of delivery method. Recommendations for research and practical application of CTD when teaching reading are provided.

The Extracellular Matrix Protein Brevican Limits Time-Dependent Enhancement of Cocaine Conditioned Place Preference.

Cocaine-associated environmental cues sustain relapse vulnerability by reactivating long-lasting memories of cocaine reward. During periods of abstinence, responding to cocaine cues can time-dependently intensify a phenomenon referred to as 'incubation of cocaine craving'. Here, we investigated the role of the extracellular matrix protein brevican in recent (1 day after training) and remote (3 weeks after training) expression of cocaine conditioned place preference (CPP). Wild-type and Brevican heterozygous knock-out mice, which express brevican at ~50% of wild-type levels, received three cocaine-context pairings using a relatively low dose of cocaine (5 mg/kg). In a drug-free CPP test, heterozygous mice showed enhanced preference for the cocaine-associated context at the remote time point compared with the recent time point. This progressive increase was not observed in wild-type mice and it did not generalize to contextual-fear memory. Virally mediated overexpression of brevican levels in the hippocampus, but not medial prefrontal cortex, of heterozygous mice prevented the progressive increase in cocaine CPP, but only when overexpression was induced before conditioning. Post-conditioning overexpression of brevican did not affect remote cocaine CPP, suggesting that brevican limited the increase in remote CPP by altering neuro-adaptive mechanisms during cocaine conditioning. We provide causal evidence that hippocampal brevican levels control time-dependent enhancement of cocaine CPP during abstinence, pointing to a novel substrate that regulates incubation of responding to cocaine-associated cues.

Structural basis for cpSRP43 chromodomain selectivity and dynamics in Alb3 insertase interaction.

Canonical membrane protein biogenesis requires co-translational delivery of ribosome-associated proteins to the Sec translocase and depends on the signal recognition particle (SRP) and its receptor (SR). In contrast, high-throughput delivery of abundant light-harvesting chlorophyll a,b-binding proteins (LHCPs) in chloroplasts to the Alb3 insertase occurs post-translationally via a soluble transit complex including the cpSRP43/cpSRP54 heterodimer (cpSRP). Here we describe the molecular mechanisms of tethering cpSRP to the Alb3 insertase by specific interaction of cpSRP43 chromodomain 3 with a linear motif in the Alb3 C-terminal tail. Combining NMR spectroscopy, X-ray crystallography and biochemical analyses, we dissect the structural basis for selectivity of chromodomains 2 and 3 for their respective ligands cpSRP54 and Alb3, respectively. Negative cooperativity in ligand binding can be explained by dynamics in the chromodomain interface. Our study provides a model for membrane recruitment of the transit complex and may serve as a prototype for a functional gain by the tandem arrangement of chromodomains.