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The autoimmune regulator (AIRE) induces the transcription of thousands of peripheral tissue genes (PTGs) in thymic epithelial cells (TECs) to mediate immunological tolerance. The chromatin state required for optimal AIRE function in TECs and how this state is induced remains unclear. We tested the role of the histone acetyltransferase, KAT7 (also known as HBO1 or MYST2), which is essential for acetylation of histone 3 lysine 14, in TEC differentiation, AIRE-mediated PTG expression, and thymic tolerance. We find that KAT7 is required for optimal expansion of medullary TEC and has a major role in the expression of AIRE-dependent PTGs, associated with enhanced chromatin accessibility at these gene loci in TECs. Mice with TEC-specific Kat7 deletion develop organ-specific autoimmunity with features resembling those observed in Aire-deficient mice. These findings highlight critical roles for KAT7-mediated acetylation in promoting a chromatin state at PTG loci that enables AIRE function and the establishment of immunological tolerance. [ABSTRACT FROM AUTHOR]

Background: eGFR equations are used to monitor progression of kidney disease, but their performance is incompletely understood in young adults with T1D and preserved GFR. To address this deficit, we compared two eGFR equations (creatinine-based CKD-EPI and modified Schwartz) to mGFR in this population. Methods: GFR based on plasma iohexol clearance was measured in 53 patients (24 males) with T1D, as part of the CAN-SOLVE CKD study Results: Mean age was 20.6±2.1 yrs with mean diabetes duration of 13.1±3.3 yrs. Mean HbA1c and ACR were 8.1±1.3 and 1.6±1.9 mg/mmol, respectively. Mean mGFR was 107.6±15.9 ml/min/1.73 m2. The Schwartz eGFR had a smaller mean bias (5.6 vs. 27.4 ml/min/1.73m2), better accuracy, and overall correlation compared to the CKD-EPI eGFR, while the latter had slightly superior precision. However, both equations were in poor agreement with mGFR. Examination of the Bland Altman plots reveals that, in the lower normal range, the CKD-EPI equation overestimated mGFR. The modified Schwartz equation showed no discernible tendencies. Conclusion: In young adults with T1D and preserved GFR, the modified Schwartz eGFR performed slightly better than CKD-EPI eGFR. Overall, however, both were in poor agreement with mGFR suggesting caution about the use of eGFR as a surrogate outcome in longitudinal studies and emphasizing the need to develop novel equations for this population. Disclosure: K. Gaebe: None. C. A. White: None. F. H. Mahmud: Advisory Panel; Self; Insulet Corporation, Lilly Diabetes. J. W. Scholey: None. L. Motran: None. M. Palaganas: None. Y. T. Elia: None. D. Cherney: Other Relationship; Self; AbbVie Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Janssen Scientific Affairs, LLC., Lilly Diabetes, Merck & Co., Inc., Mitsubishi-Tanabe, Maze Inc, Prometic, Novo Nordisk, Sanofi. E. B. Sochett: None. Funding: Canadian Institutes of Health Research (20R26070); JDRF [ABSTRACT FROM AUTHOR]

This article includes comments on each contributing author's article in this special issue of Humor. The articles represent an assessment of McGhee's research, work on practical applications or influence in the following areas: 1) the development of children's humor, 2) construction and validation of the Sense of Humor Scale (SHS), 3) usefulness of specific subscales of the SHS, including "playfulness" and "laughing at yourself," 4) development and evaluation of the 7 Humor Habits Program—a training program for learning to use humor to cope with stress, 5) humor's impact on physical health and emotional well being, 6) impact on the field of nursing, and 7) humor and the brain. McGhee provides here his response to each contributed article. [ABSTRACT FROM AUTHOR]