784 research outputs found
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: 0.87â1.08, p-value = 0.55) for zinc to 1.07 (95% CI: 1.00â1.14, p-value = 0.06)âi.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: 0.87â1.09, p-value = 0.66) for vitamin K(1) to 1.07 (95% CI: 0.88â1.29, p-value = 0.49) for copper, and from 0.93 (95% CI: 0.72â1.19, p-value = 0.55) for vitamin K(1) to 1.21 (95% CI: 0.79â1.86, 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 âSobczyk, 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 textilesâstress 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 anotherâwere found insignificant in typical textile display environments unless the textiles are severely degraded or excessively strained in their mounting
Angular distributions in Monte Carlo event generation of weak single-pion production
One of the substantial sources of systematic errors in neutrino oscillation
experiments that utilize neutrinos from accelerator sources stems from a lack
of precision in modeling single-pion production (SPP). Oscillation analyses
rely on Monte Carlo event generators (MC), providing theoretical predictions of
neutrino interactions on nuclear targets. Pions produced in these processes
provide a significant fraction of oscillation signal and background on both
elementary scattering and detector simulation levels. Thus, it is of critical
importance to develop techniques that will allow us to accommodate
state-of-the-art theoretical models describing SPP into MCs.
In this work, we investigate various algorithms to implement single-pion
production models in Monte Carlo event generators. Based on comparison studies,
we propose a novel implementation strategy that combines satisfactory
efficiency with high precision in reproducing details of theoretical models
predictions, including pion angular distributions. The proposed implementation
is model-independent, thereby providing a framework that can include any model
for SPP. We have tested the new algorithm with the Ghent Low Energy Model for
single-pion production implemented in the NuWro Monte Carlo event generator.Comment: 13 pages, 8 figure
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