Unc13A dynamically stabilizes vesicle priming at synaptic release sites for short-term facilitation and homeostatic potentiation

Summary: Presynaptic plasticity adjusts neurotransmitter (NT) liberation. Short-term facilitation (STF) tunes synapses to millisecond repetitive activation, while presynaptic homeostatic potentiation (PHP) of NT release stabilizes transmission over minutes. Despite different timescales of STF and PHP, our analysis of Drosophila neuromuscular junctions reveals functional overlap and shared molecular dependence on the release-site protein Unc13A. Mutating Unc13A’s calmodulin binding domain (CaM-domain) increases baseline transmission while blocking STF and PHP. Mathematical modeling suggests that Ca2+/calmodulin/Unc13A interaction plastically stabilizes vesicle priming at release sites and that CaM-domain mutation causes constitutive stabilization, thereby blocking plasticity. Labeling the functionally essential Unc13A MUN domain reveals higher STED microscopy signals closer to release sites following CaM-domain mutation. Acute phorbol ester treatment similarly enhances NT release and blocks STF/PHP in synapses expressing wild-type Unc13A, while CaM-domain mutation occludes this, indicating common downstream effects. Thus, Unc13A regulatory domains integrate signals across timescales to switch release-site participation for synaptic plasticity

Double-trap measurement of the proton magnetic moment at 0.3 parts per billion precision

Precise knowledge of the fundamental properties of the proton is essential for our understanding of atomic structure as well as for precise tests of fundamental symmetries. We report on a direct high-precision measurement of the magnetic moment μ_p of the proton in units of the nuclear magneton μ_N. The result, μ_p = 2.79284734462 (±0.00000000082) μ_N, has a fractional precision of 0.3 parts per billion, improves the previous best measurement by a factor of 11, and is consistent with the currently accepted value. This was achieved with the use of an optimized double–Penning trap technique. Provided a similar measurement of the antiproton magnetic moment can be performed, this result will enable a test of the fundamental symmetry between matter and antimatter in the baryonic sector at the 10⁻¹⁰ level

Progress towards an improved comparison of the proton-to-antiproton charge-to-mass ratios

High-precision comparisons of the proton-to-antiproton charge-to-mass ratios provide sensitive tests of the fundamental charge, parity, time (CPT) invariance. In 2014, we performed such a measurement with a fractional precision of 69 parts in a trillion (p.p.t.). In this article, we describe technical developments which were implemented to improve the precision of our previous measurement by at least a factor of 3

350-fold improved measurement of the antiproton magnetic moment using a multi-trap method

We summarize our recent 1.5 parts per billion measurement of the antiproton magnetic moment using the multi Penning-trap system of the BASE collaboration. The result was achieved by combining the detection of individual spin-transitions of a single antiproton with a novel two-particle spectroscopy technique, which dramatically improved the data sampling rate. This measurement contributes to improve the test of the fundamental charge, parity, time reversal (CPT) invariance in the baryon sector by a factor of 350 compared to our last measurement, and by a factor of 3000 compared to the best competing measurement. We review the measurement technique and discuss the improved limits on CPT-violating physics imposed by this measurement

C-reactive protein modifies lipoprotein(a)-related risk for coronary heart disease:the BiomarCaRE project

BACKGROUND AND AIMS: Recent investigations have suggested an interdependence of lipoprotein(a) [Lp(a)]-related risk for cardiovascular disease with background inflammatory burden. The aim the present analysis was to investigate whether high-sensitive C-reactive protein (hsCRP) modulates the association between Lp(a) and coronary heart disease (CHD) in the general population.METHODS: Data from 71 678 participants from 8 European prospective population-based cohort studies were used (65 661 without/6017 with established CHD at baseline; median follow-up 9.8/13.8 years, respectively). Fine and Gray competing risk-adjusted models were calculated according to accompanying hsCRP concentration (&lt;2 and ≥2 mg/L).RESULTS: Among CHD-free individuals, increased Lp(a) levels were associated with incident CHD irrespective of hsCRP concentration: fully adjusted sub-distribution hazard ratios [sHRs (95% confidence interval)] for the highest vs. lowest fifth of Lp(a) distribution were 1.45 (1.23-1.72) and 1.48 (1.23-1.78) for a hsCRP group of &lt;2 and ≥2 mg/L, respectively, with no interaction found between these two biomarkers on CHD risk (Pinteraction = 0.82). In those with established CHD, similar associations were seen only among individuals with hsCRP ≥ 2 mg/L [1.34 (1.03-1.76)], whereas among participants with a hsCRP concentration &lt;2 mg/L, there was no clear association between Lp(a) and future CHD events [1.29 (0.98-1.71)] (highest vs. lowest fifth, fully adjusted models; Pinteraction = 0.024).CONCLUSIONS: While among CHD-free individuals Lp(a) was significantly associated with incident CHD regardless of hsCRP, in participants with CHD at baseline, Lp(a) was related to recurrent CHD events only in those with residual inflammatory risk. These findings might guide adequate selection of high-risk patients for forthcoming Lp(a)-targeting compounds.</p