Glucose sensor O-GlcNAcylation coordinates with phosphorylation to regulate circadian clock.

Posttranslational modifications play central roles in myriad biological pathways including circadian regulation. We employed a circadian proteomic approach to demonstrate that circadian timing of phosphorylation is a critical factor in regulating complex GSK3β-dependent pathways and identified O-GlcNAc transferase (OGT) as a substrate of GSK3β. Interestingly, OGT activity is regulated by GSK3β; hence, OGT and GSK3β exhibit reciprocal regulation. Modulating O-GlcNAcylation levels alter circadian period length in both mice and Drosophila; conversely, protein O-GlcNAcylation is circadianly regulated. Central clock proteins, Clock and Period, are reversibly modified by O-GlcNAcylation to regulate their transcriptional activities. In addition, O-GlcNAcylation of a region in PER2 known to regulate human sleep phase (S662-S674) competes with phosphorylation of this region, and this interplay is at least partly mediated by glucose levels. Together, these results indicate that O-GlcNAcylation serves as a metabolic sensor for clock regulation and works coordinately with phosphorylation to fine-tune circadian clock

Circadian Control of Dendrite Morphology in the Visual System of Drosophila melanogaster

In the first optic neuropil (lamina) of the fly's visual system, monopolar cells L1 and L2 and glia show circadian rhythms in morphological plasticity. They change their size and shape during the day and night. The most pronounced changes have been detected in circadian size of the L2 axons. Looking for a functional significance of the circadian plasticity observed in axons, we examined the morphological plasticity of the L2 dendrites. They extend from axons and harbor postsynaptic sites of tetrad synaptic contacts from the photoreceptor terminals.The plasticity of L2 dendrites was evaluated by measuring an outline of the L2 dendritic trees. These were from confocal images of cross sections of L2 cells labeled with GFP. They were in wild-type and clock mutant flies held under different light conditions and sacrified at different time points. We found that the L2 dendrites are longest at the beginning of the day in both males and females. This rhythm observed under a day/night regime (LD) was maintained in constant darkness (DD) but not in continuous light (LL). This rhythm was not present in the arrhythmic per(01) mutant in LD or in DD. In the clock photoreceptor cry(b) mutant the rhythm was maintained but its pattern was different than that observed in wild-type flies.The results obtained showed that the L2 dendrites exhibit circadian structural plasticity. Their morphology is controlled by the per gene-dependent circadian clock. The L2 dendrites are longest at the beginning of the day when the daytime tetrad presynaptic sites are most numerous and L2 axons are swollen. The presence of the rhythm, but with a different pattern in cry(b) mutants in LD and DD indicates a new role of cry in the visual system. The new role is in maintaining the circadian pattern of changes of the L2 dendrite length and shape

Seasonality and spatial heterogeneity of the surface ocean carbonate system in the northwest European continental shelf

In 2014–5 the UK NERC sponsored an 18 month long Shelf Sea Biogeochemistry research programme which collected over 1500 nutrient and carbonate system samples across the NW European Continental shelf, one of the largest continental shelves on the planet. This involved the cooperation of 10 different Institutes and Universities, using 6 different vessels. Additional carbon dioxide (CO2) data were obtained from the underway systems on three of the research vessels. Here, we present and discuss these data across 9 ecohydrodynamic regions, adapted from those used by the EU Marine Strategy Framework Directive (MSFD). We observed strong seasonal and regional variability in carbonate chemistry around the shelf in relation to nutrient biogeochemistry. Whilst salinity increased (and alkalinity decreased) out from the near-shore coastal waters offshore throughout the year nutrient concentrations varied with season. Spatial and seasonal variations in the ratio of DIC to nitrate concentration were seen that could impact carbon cycling. A decrease in nutrient concentrations and a pronounced under-saturation of surface pCO2 was evident in the spring in most regions, especially in the Celtic Sea. This decrease was less pronounced in Liverpool Bay and to the North of Scotland, where nutrient concentrations remained measurable throughout the year. The near-shore and relatively shallow ecosystems such as the eastern English Channel and southern North Sea were associated with a thermally driven increase in pCO2 to above atmospheric levels in summer and an associated decrease in pH. Non-thermal processes (such as mixing and the remineralisation of organic material) dominated in winter in most regions but especially in the northwest of Scotland and in Liverpool Bay. The large database collected will improve understanding of carbonate chemistry over the North-Western European Shelf in relation to nutrient biogeochemistry, particularly in the context of climate change and ocean acidification

FOORUM: Milline on Eesti ajalooteaduse tulevik?

Kui teemanumbri seitse artiklit võtsid tagasivaatavalt vaagida Eesti ajalooteaduse arengusuundi vii­ masel kahel kümnendil, siis siinse foorumi seitse lühiesseed heidavad vastukaaluks pilgu ettepoole, arutledes Eesti ajalooteaduse võimalike suundumuste üle järgmisel kahel aastakümnel. Ettepanek foo­ rumisse panustada sai tehtud teadlikult vaid nendele eri põlvkondade Eesti ajaloolastele – doktorandist emeriitprofessoriteni –, kes on mõnda aega tegutsenud või tegutsevad praegu välismaa ülikoolides. Selle valiku taga on lihtne soov pakkuda avaramat vaadet, n­ö kõrvalt pilku, mida teises ühiskonnas töötamine eelduspäraselt pakub. Ühtlasi võib valikut käsitada tunnismärgina sellest, et uuel sajandil on üha enam Eesti ajaloolasi leidnud rakendust nimekates ülikoolides üle ilma. Tänan siinkohal toi­ metuse nimel kõiki, kes leidsid võimaluse ettepanek vastu võtta. Mõtteliselt võib siinse foorumi siduda kahekümne aasta taguse katsetusega ajakirjas Vikerkaar, kus palusin kümmekonnal Eesti ajaloolasel arutleda lühiessee vormis küsimuse üle „Kuidas kirjutada Eesti ajalugu“.1 Jääb vaid loota, et hiljemalt 2040. aastal saab see mõtteline traditsioon uue järje

Glucose sensor O-GlcNAcylation coordinates with phosphorylation to regulate circadian clock.

Posttranslational modifications play central roles in myriad biological pathways including circadian regulation. We employed a circadian proteomic approach to demonstrate that circadian timing of phosphorylation is a critical factor in regulating complex GSK3β-dependent pathways and identified O-GlcNAc transferase (OGT) as a substrate of GSK3β. Interestingly, OGT activity is regulated by GSK3β; hence, OGT and GSK3β exhibit reciprocal regulation. Modulating O-GlcNAcylation levels alter circadian period length in both mice and Drosophila; conversely, protein O-GlcNAcylation is circadianly regulated. Central clock proteins, Clock and Period, are reversibly modified by O-GlcNAcylation to regulate their transcriptional activities. In addition, O-GlcNAcylation of a region in PER2 known to regulate human sleep phase (S662-S674) competes with phosphorylation of this region, and this interplay is at least partly mediated by glucose levels. Together, these results indicate that O-GlcNAcylation serves as a metabolic sensor for clock regulation and works coordinately with phosphorylation to fine-tune circadian clock

Magnitude and Origin of the Anthropogenic CO2 Increase and the 13C Suess Effect in the Nordic Seas since 1981

This study evaluates the anthropogenic changes of CO2 (∆Cant) and δ13C (∆δ13Cant) in the Nordic seas, the northern limb of the Atlantic Meridional Overturning Circulation, that took place between 1981 and 2002/03. The changes have been determined by comparing data obtained during the Transient Tracers in the Ocean, North Atlantic Study (TTO-NAS) with data obtained during the Nordic seas surveys of R/V Knorr in 2002 and R/V G.O. Sars in 2003 using an extended multi-linear regression approach. The estimated ∆δ13Cant and ∆Cant and their relationship to each other and to water mass distribution suggest that the Polar Water entering the Nordic seas from the north is undersaturated with respect to the present atmospheric anthropogenic CO2 levels and promotes a local uptake of Cant within the Nordic seas. In contrast, the Atlantic Water entering from the south appears equilibrated. It carries with it anthropogenic carbon which will be sequestered at depth as the water overturns. This pre-equilibration leaves no room for further uptake of Cant in the parts of the Nordic seas dominated by Atlantic Water. The upper ocean pCO2 in these regions appears to have increased at a greater rate than the atmospheric pCO2 over the last two decades; this is reconcilable with a large lateral advective supply of Cant

DIXDC1 contributes to psychiatric susceptibility by regulating dendritic spine and glutamatergic synapse density via GSK3 and Wnt/β-catenin signaling.

Mice lacking DIX domain containing-1 (DIXDC1), an intracellular Wnt/β-catenin signal pathway protein, have abnormal measures of anxiety, depression and social behavior. Pyramidal neurons in these animals' brains have reduced dendritic spines and glutamatergic synapses. Treatment with lithium or a glycogen synthase kinase-3 (GSK3) inhibitor corrects behavioral and neurodevelopmental phenotypes in these animals. Analysis of DIXDC1 in over 9000 cases of autism, bipolar disorder and schizophrenia reveals higher rates of rare inherited sequence-disrupting single-nucleotide variants (SNVs) in these individuals compared with psychiatrically unaffected controls. Many of these SNVs alter Wnt/β-catenin signaling activity of the neurally predominant DIXDC1 isoform; a subset that hyperactivate this pathway cause dominant neurodevelopmental effects. We propose that rare missense SNVs in DIXDC1 contribute to psychiatric pathogenesis by reducing spine and glutamatergic synapse density downstream of GSK3 in the Wnt/β-catenin pathway