Checkpoint kinase 2 controls insulin secretion and glucose homeostasis.

After the discovery of insulin, a century ago, extensive work has been done to unravel the molecular network regulating insulin secretion. Here we performed a chemical screen and identified AZD7762, a compound that potentiates glucose-stimulated insulin secretion (GSIS) of a human ß cell line, healthy and type 2 diabetic (T2D) human islets and primary cynomolgus macaque islets. In vivo studies in diabetic mouse models and cynomolgus macaques demonstrated that AZD7762 enhances GSIS and improves glucose tolerance. Furthermore, genetic manipulation confirmed that ablation of CHEK2 in human ß cells results in increased insulin secretion. Consistently, high-fat-diet-fed Chk2-/- mice show elevated insulin secretion and improved glucose clearance. Finally, untargeted metabolic profiling demonstrated the key role of the CHEK2-PP2A-PLK1-G6PD-PPP pathway in insulin secretion. This study successfully identifies a previously unknown insulin secretion regulating pathway that is conserved across rodents, cynomolgus macaques and human ß cells in both healthy and T2D conditions.

Authorship in Urology: A Gender Reveal.

OBJECTIVE: To evaluate female author representation in urologic literature as compared to the proportion of female practicing urologists. METHODS: A cross-sectional study was designed to analyze trends in women authorship of urology publications in 2019 as compared to AUA 2019 census data. The 5 highest impact urologic journals in 2019 were identified using the publicly available SCImago Journal Rank (SJR) indices. Author genders and study categorization were independently determined by 2 authors. Chi-squared test was used for statistical analyses. RESULTS: The 5 highest impact urologic journals in 2019 as per SJR were European Urology, Journal of Urology, British Journal of Urology International, Prostate Cancer and Prostatic Diseases, and Nature Reviews Urology. A total of 501 publications were included for analysis. Women comprised 22.1% of first authors and 14.6% of senior authors. The proportion of publications authored by women was significantly higher than would be expected based on population proportions from the AUA 2019 census data for women as both first (P < .0001) and senior author (P =.0005). Similarly, women authorship was significantly higher than expected for basic science (P < .0001), clinical medicine (P <.0001), economics/practice management (P =.0002), editorial (P =.0027), and review/meta-analysis (P <.0001) publications. CONCLUSION: The present study demonstrates that women contribute to the urologic literature significantly more than would be expected based on the proportion of practicing female urologists. However, with the persistence of gender gap in academic medicine promotions, further research into contributing factors and strategies for improvement are needed to promote greater women representation in academia.

Male germ cells support long-term propagation of Zika virus.

Evidence of male-to-female sexual transmission of Zika virus (ZIKV) and viral RNA in semen and sperm months after infection supports a potential role for testicular cells in ZIKV propagation. Here, we demonstrate that germ cells (GCs) are most susceptible to ZIKV. We found that only GCs infected by ZIKV, but not those infected by dengue virus and yellow fever virus, produce high levels of infectious virus. This observation coincides with decreased expression of interferon-stimulated gene Ifi44l in ZIKV-infected GCs, and overexpression of Ifi44l results in reduced ZIKV production. Using primary human testicular tissue, we demonstrate that human GCs are also permissive for ZIKV infection and production. Finally, we identified berberine chloride as a potent inhibitor of ZIKV infection in both murine and human testes. Together, these studies identify a potential cellular source for propagation of ZIKV in testes and a candidate drug for preventing sexual transmission of ZIKV.