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Purine nucleosides on position 9 of eukaryal and archaeal tRNAs are frequently modified in vivo by the post-transcriptional addition of a methyl group on their N1 atom. The methyltransferase Trm10 is responsible for this modification in both these domains of life. While certain Trm10 orthologues specifically methylate either guanosine or adenosine at position 9 of tRNA, others have a dual specificity. Until now structural information about this enzyme family was only available for the catalytic SPOUT domain of Trm10 proteins that show specificity toward guanosine. Here, we present the first crystal structure of a full length Trm10 orthologue specific for adenosine, revealing next to the catalytic SPOUT domain also N- and C-terminal domains. This structure hence provides crucial insights in the tRNA binding mechanism of this unique monomeric family of SPOUT methyltransferases. Moreover, structural comparison of this adenosine-specific Trm10 orthologue with guanosine-specific Trm10 orthologues suggests that the N1 methylation of adenosine relies on additional catalytic residues.

Objectives: This study examines the effects of sleep restricted to four hours for three consecutive nights on blood parameters, known to be associated with cardiovascular risk, in young healthy men. Material and methods: Eight young healthy men (age 24.5 ± 3.3 years) were studied in the sleep restricted group. Nine young healthy men (age 24 ± 2 years) were included in the control group and spent the days and nights in the sleep lab, while sleeping eight hours/night. One baseline night was followed by three nights of sleep restriction to four hours and by one recovery night of eight hours. Blood samplings were performed after the baseline night and after the third night of sleep restriction or without restriction for the control group. Results: A signifi cant increase in white blood cells (WBC) (5.79 ± 1.05 vs. 6.89 ± 1.31 10 3 cell/μl, p = 0.03), and neutrophils (3.17 ± 0.69 vs 4.24 ± 0.97 10 3 cell/μl, p = 0.01) was observed after the third night of sleep restriction. Other blood parameters were not affected. No signifi cant variation was observed in the control group. Conclusion: Sleep restriction affected WBC count, mainly neutrophils, considered as risk factor for cardiovascular disease. Stress induced by the short term sleep restriction could be involved in this observation.

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ObjectivesMany studies have evaluated the ways in which sleep disturbances may influence inflammation and the possible links of this effect to cardiovascular risk. Our objective was to investigate the effects of chronic sleep restriction and recovery on several blood cardiovascular biomarkers.Methods and ResultsNine healthy male non-smokers, aged 22–29 years, were admitted to the Sleep Laboratory for 11 days and nights under continuous electroencephalogram polysomnography. The study consisted of three baseline nights of 8 hours sleep (from 11 pm to 7 am), five sleep-restricted nights, during which sleep was allowed only between 1 am and 6 am, and three recovery nights of 8 hours sleep (11 pm to 7 am). Myeloperoxidase-modified low-density lipoprotein levels increased during the sleep-restricted period indicating an oxidative stress. A significant increase in the quantity of slow-wave sleep was measured during the first recovery night. After this first recovery night, insulin-like growth factor-1 levels increased and myeloperoxidase concentration peaked.ConclusionsWe observed for the first time that sleep restriction and the recovery process are associated with differential changes in blood biomarkers of cardiovascular disease.

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