Obstacles to Success of Students with Autism Spectrum Disorder in General Education Settings

The purpose of this study was to survey teacher opinions of 14 potential obstacles to teaching in general education classes attended by students with autism spectrum disorder (ASD). The anonymous participant responses were received from 16 elementary school teachers, 60 middle school teachers, and 131 high school teachers. Participants completed a questionnaire in which they rated 14 items. Rating data were uploaded to STATA data analysis software. The Kruskal-Wallis (K-W) statistic was used to analyze and interpret the data. Results identified items that significantly discriminated among teachers of the three grade levels and show a difference in the perceptions of teachers at different grade levels for some obstacles. Teachers at the elementary school level generally perceived greater obstacles than teachers at the middle school level, who perceived greater obstacles than those at the high school level. The results can be considered by educators and service providers when identifying professional development topics and resources to assist educators and service providers in the provision of instruction to maximize the potential for academic and social success for students with ASD in general education settings

Strategies to Promote Meaningful Student Engagement in Online Settings

Distance learning or online education has increased significantly over the past decade to coincide with easy access to technology and the availability of multifaceted learning management system software that can be used to develop asynchronous educational experiences (Ginder et al., 2018). The increased demand for online education, as well as unprecedented circumstances (Covid-19 Pandemic) that require quick changes to instructional delivery alternatives, have resulted in many traditional face-to-face programs transitioning into online and hybrid (e.g., part online and part face-to-face) programs across curriculum content areas to attract and retain full and part-time learners (DuPont et al., 2018). Effective online instruction must be engaging and meaningful/relevant. Course authors and instructors in higher education must incorporate strategies to maximize student engagement to develop high-quality learning experiences in online environments (Fallahi, 2019; Weidlich & Bastiaens, 2018). This article discusses the application of varied strategies and instructional practices to help instructors in post-secondary educational settings enhance the quality of teaching and social presence in the online learning environment. The strategies addressed are connected to the teachers’ ability to integrate multifaceted learning goals into instructional planning and delivery in order to create effective online learning environments that may improve outcomes for students across settings and content areas (Dixson, 2015; Henrie et al., 2015; Moore & Shemberger, 2019)

Activating mutations of STAT5B and STAT3 in lymphomas derived from γδ-T or NK cells

Lymphomas arising from NK or γδ-T cells are very aggressive diseases and little is known regarding their pathogenesis. Here we report frequent activating mutations of STAT3 and STAT5B in NK/T-cell lymphomas (n=51), γδ-T-cell lymphomas (n=43) and their cell lines (n=9) through next generation and/or Sanger sequencing. STAT5B N642H is particularly frequent in all forms of γδ-T-cell lymphomas. STAT3 and STAT5B mutations are associated with increased phosphorylated protein and a growth advantage to transduced cell lines or normal NK cells. Growth-promoting activity of the mutants can be partially inhibited by a JAK1/2 inhibitor. Molecular modelling and surface plasmon resonance measurements of the N642H mutant indicate a marked increase in binding affinity of the phosphotyrosine-Y699 with the mutant histidine. This is associated with the prolonged persistence of the mutant phosphoSTAT5B and marked increase of binding to target sites. Our findings suggest that JAK-STAT pathway inhibition may represent a therapeutic strategy. © 2015 Macmillan Publishers Limited. All rights reserved

Activating mutations of STAT5B and STAT3 in lymphomas derived from gamma delta-T or NK cells

Peer reviewe

Antagonist HIV-1 Gag Peptides Induce Structural Changes in HLA B8

In the cellular immune response, recognition by CTL-TCRs of viral antigens presented as peptides by HLA class I molecules, triggers destruction of the virally infected cell (Townsend, A.R.M., J. Rothbard, F.M. Gotch, G. Bahadur, D. Wraith, and A.J. McMichael. 1986. Cell. 44:959–968). Altered peptide ligands (APLs) which antagonise CTL recognition of infected cells have been reported (Jameson, S.C., F.R. Carbone, and M.J. Bevan. 1993. J. Exp. Med. 177:1541–1550). In one example, lysis of antigen presenting cells by CTLs in response to recognition of an HLA B8–restricted HIV-1 P17 (aa 24–31) epitope can be inhibited by naturally occurring variants of this peptide, which act as TCR antagonists (Klenerman, P., S. Rowland Jones, S. McAdam, J. Edwards, S. Daenke, D. Lalloo, B. Koppe, W. Rosenberg, D. Boyd, A. Edwards, P. Giangrande, R.E. Phillips, and A. McMichael. 1994. Nature (Lond.). 369:403– 407). We have characterised two CTL clones and a CTL line whose interactions with these variants of P17 (aa 24–31) exhibit a variety of responses. We have examined the high resolution crystal structures of four of these APLs in complex with HLA B8 to determine alterations in the shape, chemistry, and local flexibility of the TCR binding surface. The variant peptides cause changes in the recognition surface by three mechanisms: changes contributed directly by the peptide, effects transmitted to the exposed peptide surface, and induced effects on the exposed framework of the peptide binding groove. While the first two mechanisms frequently lead to antagonism, the third has more profound effects on TCR recognition

The Goldilocks Model for TCR—Too Much Attraction Might Not Be Best for Vaccine Design

Recent research on T cell-antigen interactions suggests that tighter binding is not always better at eliciting an effective immune response

A Role for Rebinding in Rapid and Reliable T Cell Responses to Antigen

Experimental work has shown that T cells of the immune system rapidly and specifically respond to antigenic molecules presented on the surface of antigen-presenting-cells and are able to discriminate between potential stimuli based on the kinetic parameters of the T cell receptor-antigen bond. These antigenic molecules are presented among thousands of chemically similar endogenous peptides, raising the question of how T cells can reliably make a decision to respond to certain antigens but not others within minutes of encountering an antigen presenting cell. In this theoretical study, we investigate the role of localized rebinding between a T cell receptor and an antigen. We show that by allowing the signaling state of individual receptors to persist during brief unbinding events, T cells are able to discriminate antigens based on both their unbinding and rebinding rates. We demonstrate that T cell receptor coreceptors, but not receptor clustering, are important in promoting localized rebinding, and show that requiring rebinding for productive signaling reduces signals from a high concentration of endogenous pMHC. In developing our main results, we use a relatively simple model based on kinetic proofreading. However, we additionally show that all our results are recapitulated when we use a detailed T cell receptor signaling model. We discuss our results in the context of existing models and recent experimental work and propose new experiments to test our findings

Enhancement of Transport Selectivity through Nano-Channels by Non-Specific Competition

The functioning of living cells requires efficient and selective transport of materials into and out of the cell, and between different cellular compartments. Much of this transport occurs through nano-scale channels that do not require large scale molecular re-arrangements (such as transition from a ‘closed’ to an ‘open’ state) and do not require a direct input of metabolic energy during transport. Nevertheless, these ‘always open’ channels are highly selective and pass only their cognate molecules, while efficiently excluding all others; indeed, these channels can efficiently transport specific molecules even in the presence of a vast excess of non-specific molecules. Such biological transporters have inspired the creation of artificial nano-channels. These channels can be used as nano-molecular sorters, and can also serve as testbeds for examining modes of biological transport. In this paper, we propose a simple kinetic mechanism that explains how the selectivity of such ‘always open’ channels can be based on the exclusion of non-specific molecules by specific ones, due to the competition for limited space inside the channel. The predictions of the theory account for the behavior of the nuclear pore complex and of artificial nanopores that mimic its function. This theory provides the basis for future work aimed at understanding the selectivity of various biological transport phenomena