NMDA receptor subunit-dependent [Ca2+] signaling in individual hippocampal dendritic spines

Ca2+ influx through synaptic NMDA receptors (NMDA-Rs) triggers a variety of adaptive cellular processes. To probe NMDA-R-mediated [Ca2+] signaling, we used two-photon glutamate uncaging to stimulate NMDA-Rs on individual dendritic spines of CA1 pyramidal neurons in rat brain slices. We measured NMDA-R currents at the soma and NMDA-R-mediated [Ca2+] transients in stimulated spines (Delta[Ca2+]). Uncaging-evoked NMDA-R current amplitudes were independent of the size of the stimulated spine, implying that smaller spines contain higher densities of functional NMDA-Rs. The ratio of Delta[Ca2+] over NMDA-R current was highly variable (factor of 10) across spines, especially for small spines. These differences were not explained by heterogeneity in spine sizes or diffusional coupling between spines and their parent dendrites. In addition, we find that small spines have NMDA-R currents that are sensitive to NMDA-R NR2B subunit-specific antagonists. With block of NR2B-containing receptors, the range of Delta[Ca2+]/NMDA-R current ratios and their average value were much reduced. Our data suggest that individual spines can regulate the subunit composition of their NMDA-Rs and the effective fractional Ca2+ current through these receptors

Theory of STM junctions for \pi-conjugated molecules on thin insulating films

A microscopic theory of the transport in a scanning tunnelling microscope (STM) set-up is introduced for \pi-conjugated molecules on insulating films, based on the density matrix formalism. A key role is played in the theory by the energy dependent tunnelling rates which account for the coupling of the molecule to the tip and to the substrate. In particular, we analyze how the geometrical differences between the localized tip and extended substrate are encoded in the tunnelling rate and influence the transport characteristics. Finally, using benzene as an example of a planar, rotationally symmetric molecule, we calculate the STM current voltage characteristics and current maps and analyze them in terms of few relevant angular momentum channels.Comment: 19 pages, 12 figures, minor changes to conform to published versio

The Effect of Circulating Zinc, Selenium, Copper and Vitamin K1 on COVID-19 Outcomes:A Mendelian Randomization Study

Background & Aims: Previous results from observational, interventional studies and in vitro experiments suggest that certain micronutrients possess anti-viral and immunomodulatory activities. In particular, it has been hypothesized that zinc, selenium, copper and vitamin K(1) have strong potential for prophylaxis and treatment of COVID-19. We aimed to test whether genetically predicted Zn, Se, Cu or vitamin K(1) levels have a causal effect on COVID-19 related outcomes, including risk of infection, hospitalization and critical illness. Methods: We employed a two-sample Mendelian Randomization (MR) analysis. Our genetic variants derived from European-ancestry GWAS reflected circulating levels of Zn, Cu, Se in red blood cells as well as Se and vitamin K(1) in serum/plasma. For the COVID-19 outcome GWAS, we used infection, hospitalization or critical illness. Our inverse-variance weighted (IVW) MR analysis was complemented by sensitivity analyses including a more liberal selection of variants at a genome-wide sub-significant threshold, MR-Egger and weighted median/mode tests. Results: Circulating micronutrient levels show limited evidence of association with COVID-19 infection, with the odds ratio [OR] ranging from 0.97 (95% CI: 0.87–1.08, p-value = 0.55) for zinc to 1.07 (95% CI: 1.00–1.14, p-value = 0.06)—i.e., no beneficial effect for copper was observed per 1 SD increase in exposure. Similarly minimal evidence was obtained for the hospitalization and critical illness outcomes with OR from 0.98 (95% CI: 0.87–1.09, p-value = 0.66) for vitamin K(1) to 1.07 (95% CI: 0.88–1.29, p-value = 0.49) for copper, and from 0.93 (95% CI: 0.72–1.19, p-value = 0.55) for vitamin K(1) to 1.21 (95% CI: 0.79–1.86, p-value = 0.39) for zinc, respectively. Conclusions: This study does not provide evidence that supplementation with zinc, selenium, copper or vitamin K(1) can prevent SARS-CoV-2 infection, critical illness or hospitalization for COVID-19

Reply to Janssen et al. Comment on “Sobczyk, M.K.; Gaunt, T.R. The Effect of Circulating Zinc, Selenium, Copper and Vitamin K1 on COVID-19 Outcomes: A Mendelian Randomization Study. Nutrients 2022, 14, 233

In their correspondence arising from our recent manuscript [...

Nonlinear [Ca2+] signaling in dendrites and spines caused by activity-dependent depression of Ca2+ extrusion

Spine Ca2+ triggers the induction of synaptic plasticity and other adaptive neuronal responses. The amplitude and time course of Ca2+ signals specify the activation of the signaling pathways that trigger different forms of plasticity such as long-term potentiation and depression. The shapes of Ca2+ signals are determined by the dynamics of Ca2+ sources, Ca2+ buffers, and Ca2+ extrusion mechanisms. Here we show in rat CA1 pyramidal neurons that plasma membrane Ca2+ pumps (PMCAs) and Na+/Ca2+ exchangers are the major Ca2+ extrusion pathways in spines and small dendrites. Surprisingly, we found that Ca2+ extrusion via PMCA and Na+/Ca2+ exchangers slows in an activity-dependent manner, mediated by intracellular Na+ and Ca2+ accumulations. This activity-dependent depression of Ca2+ extrusion is, in part, attributable to Ca2+-dependent inactivation of PMCAs. Ca2+ extrusion recovers from depression with a time constant of 0.5 s. Depression of Ca2+ extrusion provides a positive feedback loop, converting small differences in stimuli into large differences in Ca2+ concentration. Depression of Ca2+ extrusion produces Ca2+ concentration dynamics that depend on the history of neuronal activity and therefore likely modulates the induction of synaptic plasticity

Risk of climate-induced damage in historical textiles

Eleven wool and silk historic textiles and two modern artist's canvases were examined to determine their water vapour adsorption, moisture dimensional response and tensile behaviour. All the textiles showed a similar general pattern of moisture response. A rise in ambient relative humidity (RH) from dry conditions produced expansion of a textile until a certain critical RH level after which a contraction occurred to a greater or lesser degree depending on the yarn crimp and the weave geometry. The largest expansion recorded between the dry state and 80% RH was 1.2 and 0.9% for wool and silk textiles, respectively. The largest shrinkage of 0.8% at high RH range was experienced by a modern linen canvas. Two potential damage mechanisms related to the moisture response of the textiles—stress building as a result of shrinkage of the textile restrained in its dimensional response and the fretting fatigue when yarns move with friction one against another—were found insignificant in typical textile display environments unless the textiles are severely degraded or excessively strained in their mounting

C5AC_5^A axial form factor from bubble chamber experiments

A careful reanalysis of both Argonne National Laboratory and Brookhaven National Laboratory data for weak single pion production is done. We consider deuteron nuclear effects and normalization (flux) uncertainties in both experiments. We demonstrate that these two sets of data are in good agreement. For the dipole parametrization of $C_5^A(Q^2)$, we obtain $C_5^A(0)=1.19\pm 0.08$, $M_A=0.94\pm 0.03$ GeV. As an application we present the discussion of the uncertainty of the neutral current 1$\pi^0$ production cross section, important for the T2K neutrino oscillation experiment.Comment: 16 pages, 8 figures, 2 table