Cerebral mGluR5 availability contributes to elevated sleep need and behavioral adjustment after sleep deprivation.

Increased sleep time and intensity quantified as low-frequency brain electrical activity after sleep loss demonstrate that sleep need is homeostatically regulated, yet the underlying molecular mechanisms remain elusive. We here demonstrate that metabotropic glutamate receptors of subtype 5 (mGluR5) contribute to the molecular machinery governing sleep-wake homeostasis. Using positron emission tomography, magnetic resonance spectroscopy, and electroencephalography in humans, we find that increased mGluR5 availability after sleep loss tightly correlates with behavioral and electroencephalographic biomarkers of elevated sleep need. These changes are associated with altered cortical myo-inositol and glycine levels, suggesting sleep loss-induced modifications downstream of mGluR5 signaling. Knock-out mice without functional mGluR5 exhibit severe dysregulation of sleep-wake homeostasis, including lack of recovery sleep and impaired behavioral adjustment to a novel task after sleep deprivation. The data suggest that mGluR5 contribute to the brain's coping mechanisms with sleep deprivation and point to a novel target to improve disturbed wakefulness and sleep

IDegLira Improves Both Fasting and Postprandial Glucose Control as Demonstrated Using Continuous Glucose Monitoring and a Standardized Meal Test

Objective: IDegLira is a novel, fixed-ratio combination of the long-acting basal insulin, insulin degludec, and the long-acting glucagon-like peptide-1 analog liraglutide. We studied the effect of IDegLira versus its components on postprandial glucose (PPG) in type 2 diabetes. Methods: In this substudy, 260 (15.6%) of the original 1663 patients with inadequate glycemic control participating in a 26-week, open-label trial (DUAL I) were randomized 2:1:1 to once-daily IDegLira, insulin degludec or liraglutide. Continuous glucose monitoring (CGM) for 72 hours and a meal test were performed. Results: At week 26, IDegLira produced a significantly greater decrease from baseline in mean PPG increment (normalized iAUC0-4h) than insulin degludec (estimated treatment difference [ETD] -'12.79 mg/dl [95% CI: -'21.08; -'4.68], P =.0023) and a similar magnitude of decrease as liraglutide (ETD -'1.62 mg/dl [95% CI: -'10.09; 6.67], P =.70). CGM indicated a greater reduction in change from baseline in PPG increment (iAUC0-4h) for IDegLira versus insulin degludec over all 3 main meals (ETD -'6.13 mg/dl [95% CI: -'10.27, -'1.98], P =.0047) and similar reductions versus liraglutide (ETD -'1.80 mg/dl [95% CI: -'2.52, 5.95], P =.4122). Insulin secretion ratio and static index were greater for IDegLira versus insulin degludec (P =.048 and P =.006, respectively) and similar to liraglutide (P =.45 and P =.895, respectively). Conclusions: Once-daily IDegLira provides significantly better PPG control following a mixed meal test than insulin degludec. The improvement is at least partially explained by higher endogenous insulin secretion and improved beta cell function with IDegLira. The benefits of liraglutide on PPG control are maintained across all main meals in the combination

Origins of the Ambient Solar Wind: Implications for Space Weather

The Sun's outer atmosphere is heated to temperatures of millions of degrees, and solar plasma flows out into interplanetary space at supersonic speeds. This paper reviews our current understanding of these interrelated problems: coronal heating and the acceleration of the ambient solar wind. We also discuss where the community stands in its ability to forecast how variations in the solar wind (i.e., fast and slow wind streams) impact the Earth. Although the last few decades have seen significant progress in observations and modeling, we still do not have a complete understanding of the relevant physical processes, nor do we have a quantitatively precise census of which coronal structures contribute to specific types of solar wind. Fast streams are known to be connected to the central regions of large coronal holes. Slow streams, however, appear to come from a wide range of sources, including streamers, pseudostreamers, coronal loops, active regions, and coronal hole boundaries. Complicating our understanding even more is the fact that processes such as turbulence, stream-stream interactions, and Coulomb collisions can make it difficult to unambiguously map a parcel measured at 1 AU back down to its coronal source. We also review recent progress -- in theoretical modeling, observational data analysis, and forecasting techniques that sit at the interface between data and theory -- that gives us hope that the above problems are indeed solvable.Comment: Accepted for publication in Space Science Reviews. Special issue connected with a 2016 ISSI workshop on "The Scientific Foundations of Space Weather." 44 pages, 9 figure

Apomixis conferred by expression of SERK interacting proteins

The present invention relates to a method for increasing the probability of vegetative reproduction of a new plant generation by transgenic expression of a gene encoding a protein acting in the signal transduction cascade triggered by the Somatic Embryogenesis Receptor Kinase (SERK). Apomictic seeds resulting therefrom, plants and progeny obtained through germination of such seeds, and genes encoding proteins acting in the signal transduction cascade triggered by SERK constitute further subject matters of the invention

Apomixis conferred by expression of SERK interacting proteins

The present invention relates to a method for increasing the probability of vegetative reproduction of a new plant generation by transgenic expression of a gene encoding a protein acting in the signal transduction cascade triggered by the Somatic Embryogenesis Receptor Kinase (SERK). Apomictic seeds resulting therefrom, plants and progeny obtained through germination of such seeds, and genes encoding proteins acting in the signal transduction cascade triggered by SERK constitute further subject matters of the invention