Autoantibodies against NMDAR subunit NR1 disappear from blood upon anesthesia

Anesthetics penetrate the blood-brain-barrier (BBB) and - as confirmed preclinically – transiently disrupt it. An analogous consequence in humans has remained unproven. In mice, we previously reported that upon BBB dysfunction, the brain acts as ‘immunoprecipitator’ of autoantibodies against N-methyl-D-aspartate-receptor subunit-NR1 (NMDAR1-AB). We thus hypothesized that during human anesthesia, pre-existing NMDAR1-AB will specifically bind to brain. Screening of N = 270 subjects undergoing general anesthesia during cardiac surgery for serum NMDAR1-AB revealed N = 25 NMDAR1-AB seropositives. Only N = 14 remained positive post-surgery. No changes in albumin, thyroglobulin or CRP were associated with reduction of serum NMDAR1-AB. Thus, upon anesthesia, BBB opening likely occurs also in humans

Efficient Numerical Self-consistent Mean-field Approach for Fermionic Many-body Systems by Polynomial Expansion on Spectral Density

We propose an efficient numerical algorithm to solve Bogoliubov de Gennes equations self-consistently for inhomogeneous superconducting systems with a reformulated polynomial expansion scheme. This proposed method is applied to typical issues such as a vortex under randomly distributed impurities and a normal conducting junction sandwiched between superconductors. With various technical remarks, we show that its efficiency becomes remarkable in large-scale parallel performance.Comment: 16 pages, 5 figures (published version

Ablation of Ventricular Myosin Regulatory Light Chain Phosphorylation in Mice Causes Cardiac Dysfunction in Situ and Affects Neighboring Myofilament Protein Phosphorylation*

There is little direct evidence on the role of myosin regulatory light chain phosphorylation in ejecting hearts. In studies reported here we determined the effects of regulatory light chain (RLC) phosphorylation on in situ cardiac systolic mechanics and in vitro myofibrillar mechanics. We compared data obtained from control nontransgenic mice (NTG) with a transgenic mouse model expressing a cardiac specific nonphosphorylatable RLC (TG-RLC(P-). We also determined whether the depression in RLC phosphorylation affected phosphorylation of other sarcomeric proteins. TG-RLC(P-) demonstrated decreases in base-line load-independent measures of contractility and power and an increase in ejection duration together with a depression in phosphorylation of myosin-binding protein-C (MyBP-C) and troponin I (TnI). Although TG-RLC(P-) displayed a significantly reduced response to β1-adrenergic stimulation, MyBP-C and TnI were phosphorylated to a similar level in TG-RLC(P-) and NTG, suggesting cAMP-dependent protein kinase signaling to these proteins was not disrupted. A major finding was that NTG controls were significantly phosphorylated at RLC serine 15 following β1-adrenergic stimulation, a mechanism prevented in TG-RLC(P-), thus providing a biochemical difference in β1-adrenergic responsiveness at the level of the sarcomere. Our measurements of Ca2+ tension and Ca2+-ATPase rate relations in detergent-extracted fiber bundles from LV trabeculae demonstrated a relative decrease in maximum Ca2+-activated tension and tension cost in TG-RLC(P-) fibers, with no change in Ca2+ sensitivity. Our data indicate that RLC phosphorylation is critical for normal ejection and response to β1-adrenergic stimulation. Our data also indicate that the lack of RLC phosphorylation promotes compensatory changes in MyBP-C and TnI phosphorylation, which when normalized do not restore function