Crossover recombination facilitates accurate segregation of homologous chromosomes during meiosis1,2. In mammals, poorly characterized regulatory processes ensure every pair of chromosomes obtains at least one crossover, even though the majority of recombination sites yield non-crossovers3. Designation of crossovers involves selective localization of SUMO-ligase RNF212 to a minority of recombination sites where it stabilizes pertinent factors, such as MutSγ4. Here we show ubiquitin-ligase HEI10/CCNB1IP15,6 is essential for this crossover/non-crossover differentiation process. In Hei10 mutant mice, RNF212 localizes to most recombination sites and dissociation of RNF212 and MutSγ from chromosomes is blocked. Consequently, recombination is impeded and crossing-over fails. In wild-type mice, HEI10 accumulates at designated crossover sites suggesting a late role to implement crossing-over. Like RNF212, dosage-sensitivity indicates HEI10 is a limiting factor for crossing-over. We suggest SUMO and ubiquitin play antagonistic roles during meiotic recombination that are balanced to effect differential stabilization of recombination factors at crossover and non-crossover sites.

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Aims We determined whether high diabetes distress (DD) in young adults with type 1 diabetes was associated with higher glycated haemoglobin (HbA1c) levels and whether this association was similar among those who were and were not using diabetes devices (insulin pumps and/or continuous glucose monitors [CGMs]). Methods In 2017, an online survey was completed by 423 of 743 (57%) young adults (19–31 years) with type 1 diabetes receiving care at a specialty clinic in New York City. HbA1c level was the primary outcome measure, and high DD (Diabetes Distress Scale score ≥3) was the primary exposure. Associations were adjusted for sociodemographic covariates. Results Of the 419 respondents with complete DD data, 59% were female and 69% were non‐Hispanic white. Both devices (pump and CGM) were used by 35%, either device by 42% and neither device by 24%. The mean (SD) HbA1c was 64 (19) mmol/mol (8.0 [1.7] %) and 24% had high DD. The adjusted mean (95% confidence interval) HbA1c was 10 (6, 14) mmol/mol (0.9 [0.5, 1.2] %) greater in those with high DD than in those without it. This HbA1c difference associated with high DD was similar regardless of device use: 9 (3, 15) mmol/mol (0.8 [0.3, 1.4] %) greater among those using both devices; and 9 (−0.9, 18) mmol/mol (0.8 [−0.1, 1.7] %) greater among those using neither device. Conclusions High DD in young adults requires more attention because it is associated with higher HbA1c levels, even among those using insulin pumps and CGMs.

IMPORTANCE Higher levels of childhood family connection have been associated with measures of adult flourishing or eudaimonic well-being, such as purpose, self-acceptance, positive relationships, and growth. However, this association has not been examined among those with childhood-onset chronic disease. OBJECTIVES To investigate whether higher levels of childhood family connection were associated with greater flourishing in young adulthood among those with type 1 diabetes and, secondarily, whether this association was present across levels of adverse childhood experiences and childhood social position.