The purpose of the study was to examine the effectiveness and feasibility of using tiered instruction to increase the frequency of conversational turn taking (CTT) among preschoolers with and without disabilities in an inclusive setting. Three CTT interventions (Universal Design for Learning, Peer Mediated Instruction, and Milieu Teaching) were organized on a hierarchy of intensity and implemented in an additive manner. Using an increasing intensity across participants with a reversal design, child progress was monitored over time and children were moved through tiers based on level of need. A functional relationship between tiered instruction and CTT was found for nine of 13 child participants and the strongest intervention effects were observed at tier one. All but one child participant showed an increase in conversational turn taking from baseline to reinstatement. Teacher fidelity of implementation was monitored at each tier. Her overall average was 90% with the highest percent occurring in tier one. Resulting contributions to the literature include a better understanding of the feasibility of tiered instruction for the inclusive early childhood classroom, the effectiveness of tiered instruction for increasing CTT, and practical considerations for implementation of tiered instruction across tiers and phase change decisions.

Abstract: The interferon (IFN)-stimulated gene product 15 (ISG15) represents an ubiquitin-like protein (Ubl), which in a process termed ISGylation can be covalently linked to target substrates via a cascade of E1, E2, and E3 enzymes. Furthermore, ISG15 exerts functions in its free form both, as an intracellular and as a secreted protein. In agreement with its role as a type I IFN effector, most functions of ISG15 and ISGylation are linked to the anti-pathogenic response. However, also key roles in other cellular processes such as protein translation, cytoskeleton dynamics, exosome secretion, autophagy or genome stability and cancer were described. Ubiquitin-specific protease 18 (USP18) constitutes the major ISG15 specific protease which counteracts ISG15 conjugation. Remarkably, USP18 also functions as a critical negative regulator of the IFN response irrespective of its enzymatic activity. Concordantly, lack of USP18 function causes fatal interferonopathies in humans and mice. The negative regulatory function of USP18 in IFN signaling is regulated by various protein-protein interactions and its stability is controlled via proteasomal degradation. The broad repertoire of physiological functions and regulation of ISG15 and USP18 offers a variety of potential intervention strategies which might be of therapeutic use. Due to the high mutation rates of pathogens which are often species specific and constantly give rise to a variety of immune evasion mechanisms, immune effector systems are under constant evolutionarily pressure. Therefore, it is not surprising that considerable differences in ISG15 with respect to function and sequence exist even among closely related species. Hence, it is essential to thoroughly evaluate the translational potential of results obtained in model organisms especially for therapeutic strategies. This review covers existing and conceptual assay systems to target and identify modulators of ISG15, ISGylation, USP18 function, and protein-protein interactions within this context. Strategies comprise mouse models for translational perspectives, cell-based and biochemical assays as well as chemical probes