Identification of Pharmacological Modulators of HMGB1-Induced Inflammatory Response by Cell-Based Screening

High mobility group box 1 (HMGB1), a highly conserved, ubiquitous protein, is released into the circulation during sterile inflammation (e.g. arthritis, trauma) and circulatory shock. It participates in the pathogenesis of delayed inflammatory responses and organ dysfunction. While several molecules have been identified that modulate the release of HMGB1, less attention has been paid to identify pharmacological inhibitors of the downstream inflammatory processes elicited by HMGB1 (C23-C45 disulfide C106 thiol form). In the current study, a cell-based medium-throughput screening of a 5000+ compound focused library of clinical drugs and drug-like compounds was performed in murine RAW264.7 macrophages, in order to identify modulators of HMGB1-induced tumor-necrosis factor alpha (TNFα) production. Clinically used drugs that suppressed HMGB1-induced TNFα production included glucocorticoids, beta agonists, and the anti-HIV compound indinavir. A re-screen of the NIH clinical compound library identified beta-agonists and various intracellular cAMP enhancers as compounds that potentiate the inhibitory effect of glucocorticoids on HMGB1-induced TNFα production. The molecular pathways involved in this synergistic anti-inflammatory effect are related, at least in part, to inhibition of TNFα mRNA synthesis via a synergistic suppression of ERK/IκB activation. Inhibition of TNFα production by prednisolone+salbutamol pretreatment was also confirmed in vivo in mice subjected to HMGB1 injection; this effect was more pronounced than the effect of either of the agents administered separately. The current study unveils several drug-like modulators of HMGB1-mediated inflammatory responses and offers pharmacological directions for the therapeutic suppression of inflammatory responses in HMGB1-dependent diseases. © 2013 Gerö et al

Personal and institutional predictors of work-life balance among women and men faculty of color

This study examines predictors of perceived work-life balance among women and men faculty of color using data from the Collaborative on Academic Careers in Higher Education (COACHE). Asian American men faculty report higher perceived work-life balance, while African American women faculty report lower perceived work-life balance as compared to other faculty members. Findings from multivariate analyses show that the strongest, most consistent positive predictor of perceived work-life balance was the faculty perception that the institution does what it can to make personal/family obligations and an academic career compatible. The findings offer important implications for institutional and departmental climate and policy

Correlates of work-life balance for faculty across racial/ethnic groups

Very few studies have examined issues of work-life balance among faculty of different racial/ethnic backgrounds. Utilizing data from Harvard University’s Collaborative on Academic Careers in Higher Education project, this study examined predictors of work-life balance for 2953 faculty members from 69 institutions. The final sample consisted of 1059 (36%) Asian American faculty, 512 (17%) African American faculty, 359 (12%) Latina/o faculty, and 1023 (35%) White/Caucasian faculty. There were 1184 (40%) women faculty and 1769 (60%) men faculty. The predictors of worklife balance included faculty characteristics, departmental/institutional characteristics and support, and faculty satisfaction with work. While African American women faculty reported less work-life balance than African American men, the reverse was true for Latina/o faculty. In addition, White faculty who were single with no children were significantly less likely to report having work-life balance than their married counterparts with children. Faculty rank was a significant positive predictor of work-life balance for all faculty. Notably, the findings highlight the importance of department and institutional support for making personal/family obligations and an academic career compatible. Institutional support for making personal/family obligations and an academic career compatible was consistently the strongest positive predictor of perceived work-life balance for all faculty. In addition, satisfaction with time spent on research had positive associations with work-life balance for all faculty, highlighting how faculty from all racial/ethnic backgrounds value being able to spend enough time on their own research