Changes in redox status are a conspicuous feature of immune responses in a variety of eukaryotes, but the associated signalling mechanisms are not well understood. In plants, attempted microbial infection triggers the rapid synthesis of nitric oxide and a parallel accumulation of reactive oxygen intermediates, the latter generated by NADPH oxidases related to those responsible for the pathogen-activated respiratory burst in phagocytes. Both nitric oxide and reactive oxygen intermediates have been implicated in controlling the hypersensitive response, a programmed execution of plant cells at sites of attempted infection. However, the molecular mechanisms that underpin their function and coordinate their synthesis are unknown. Here we show genetic evidence that increases in cysteine thiols modified using nitric oxide, termed S-nitrosothiols, facilitate the hypersensitive response in the absence of the cell death agonist salicylic acid and the synthesis of reactive oxygen intermediates. Surprisingly, when concentrations of S-nitrosothiols were high, nitric oxide function also governed a negative feedback loop limiting the hypersensitive response, mediated by S-nitrosylation of the NADPH oxidase, AtRBOHD, at Cys 890, abolishing its ability to synthesize reactive oxygen intermediates. Accordingly, mutation of Cys 890 compromised S-nitrosothiol-mediated control of AtRBOHD activity, perturbing the magnitude of cell death development. This cysteine is evolutionarily conserved and specifically S-nitrosylated in both human and fly NADPH oxidase, suggesting that this mechanism may govern immune responses in both plants and animals.

1142I.1142II.1143III.1143IV.1144V.1144VI.1145VII.1147VIII.1148IX.1149X.1149XI.1151XII.1151XIII.1152XIV.11521153References1153 Summary Nitric oxide (NO), a gaseous, redox‐active small molecule, is gradually becoming established as a central regulator of growth, development, immunity and environmental interactions in plants. A major route for the transfer of NO bioactivity is S‐nitrosylation, the covalent attachment of an NO moiety to a protein cysteine thiol to form an S‐nitrosothiol (SNO). This chemical transformation is rapidly emerging as a prototypic, redox‐based post‐translational modification integral to the life of plants. Here we review the myriad roles of NO and SNOs in plant biology and, where known, the molecular mechanisms underpining their activity.

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The independent association of eveningness with nonremission of depression suggested a significant underpinning of circadian involvement in major depressive disorder. Our findings support the need for a comprehensive assessment of sleep and circadian disturbances as well as integration of sleep and chronotherapeutic intervention in the management of depression.

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Increased sympathetic activity as measured by 24-h urinary catecholamines might play a critical role in the pathogenesis mediating the relationship of insufficient sleep (quantity and quality) with subsequent cardiovascular and metabolic complications. Salivary awakening cortisol was not associated with sleep quantity and quality in healthy middle-aged adults.

Nocturnal sleep disturbances, particularly frequent insomnia and recurrent nightmares, were independently associated with enhanced suicidal risk among psychiatric patients. Future studies are warranted to investigate the underlying pathophysiologic mechanism and interventional responses.