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The rapid adoption of generative AI in software development has impacted the industry, yet its efects on developers with visual impairments remain largely unexplored. To address this gap, we used an Activity Theory framework to examine how developers with visual impairments interact with AI coding assistants. For this purpose, we conducted a study where developers who are visually impaired completed a series of programming tasks using a generative AI coding assistant. We uncovered that, while participants found the AI assistant benefcial and reported signifcant advantages, they also highlighted accessibility challenges. Specifcally, the AI coding assistant often exacerbated existing accessibility barriers and introduced new challenges. For example, it overwhelmed users with an excessive number of suggestions, leading developers who are visually impaired to express a desire for “AI timeouts.” Additionally, the generative AI coding assistant made it more difcult for developers to switch contexts between the AI-generated content and their own code. Despite these challenges, participants were optimistic about the potential of AI coding assistants to transform the coding experience for developers with visual impairments. Our fndings emphasize the need to apply activity-centered design principles to generative AI assistants, ensuring they better align with user behaviors and address specifc accessibility needs. This approach can enable the assistants to provide more intuitive, inclusive, and efective experiences, while also contributing to the broader goal of enhancing accessibility in software developmentmore » « lessFree, publicly-accessible full text available April 25, 2026
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Ganesan, A (Ed.)Mammalian protein arginine methyltransferase 7 (PRMT7) has been shown to target substrates with motifs containing two arginine residues separated by one other residue (RXR motifs). In particular, the repression domain of human histone H2B (29-RKRSR-33) has been a key substrate in determining PRMT7 activity. We show that incubating human PRMT7 and [3H]-AdoMet with full-lengthXenopus laevishistone H2B, containing the substitutions K30R and R31K (RKRSR to RRKSR), results in greatly reduced methylation activity. Using synthetic peptides, we have now focused on the enzymology behind this specificity. We show for the human and Xenopus peptide sequences 23–37 the difference in activity results from changes in the Vmaxrather than the apparent binding affinity of the enzyme for the substrates. We then characterized six additional peptides containing a single arginine or a pair of arginine residues flanked by glycine and lysine residues. We have corroborated previous findings that peptides with an RXR motif have much higher activity than peptides that contain only one Arg residue. We show that these peptides have similar apparent kmvalues but significant differences in their Vmaxvalues. Finally, we have examined the effect of ionic strength on these peptides. We found the inclusion of salt had little effect on the Vmaxvalue but a considerable increase in the apparent kmvalue, suggesting that the inhibitory effect of ionic strength on PRMT7 activity occurs largely by decreasing apparent substrate-enzyme binding affinity. In summary, we find that even subtle substitutions in the RXR recognition motif can dramatically affect PRMT7 catalysis.more » « less
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Inflammation and oxidative stress in pancreatic islets amplify the appearance of various posttranslational modifications to self-proteins. In this study, we identified a select group of carbonylated islet proteins arising before the onset of hyperglycemia in NOD mice. Of interest, we identified carbonyl modification of the prolyl-4-hydroxylase β subunit (P4Hb) that is responsible for proinsulin folding and trafficking as an autoantigen in both human and murine type 1 diabetes. We found that carbonylated P4Hb is amplified in stressed islets coincident with decreased glucose-stimulated insulin secretion and altered proinsulin-to-insulin ratios. Autoantibodies against P4Hb were detected in prediabetic NOD mice and in early human type 1 diabetes prior to the onset of anti-insulin autoimmunity. Moreover, we identify autoreactive CD4+ T-cell responses toward carbonyl-P4Hb epitopes in the circulation of patients with type 1 diabetes. Our studies provide mechanistic insight into the pathways of proinsulin metabolism and in creating autoantigenic forms of insulin in type 1 diabetes.more » « less
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