CAPS-1 and CAPS-2 are essential synaptic vesicle priming proteins

SummaryBefore transmitter-filled synaptic vesicles can fuse with the plasma membrane upon stimulation they have to be primed to fusion competence. The regulation of this priming process controls the strength and plasticity of synaptic transmission between neurons, which in turn determines many complex brain functions. We show that CAPS-1 and CAPS-2 are essential components of the synaptic vesicle priming machinery. CAPS-deficient neurons contain no or very few fusion competent synaptic vesicles, which causes a selective impairment of fast phasic transmitter release. Increases in the intracellular Ca2+ levels can transiently revert this defect. Our findings demonstrate that CAPS proteins generate and maintain a highly fusion competent synaptic vesicle pool that supports phasic Ca2+ triggered release of transmitters

Switching between dynamic states in intermediate-length Josephson junctions

The appearance of zero-field steps (ZFS’s) in the current-voltage characteristics of intermediate-length overlap-geometry Josephson tunnel junctions described by a perturbed sine-Gordon equation (PSGE) is associated with the growth of parametrically excited instabilities of the McCumber background curve (MCB). A linear stability analysis of a McCumber solution of the PSGE in the asymptotic linear region of the MCB and in the absence of magnetic field yields a Hill’s equation which predicts how the number, locations, and widths of the instability regions depend on the junction parameters. A numerical integration of the PSGE in terms of truncated series of time-dependent Fourier spatial modes verifies that the parametrically excited instabilities of the MCB evolve into the fluxon oscillations characteristic of the ZFS’s. An approximate analysis of the Fourier mode equations in the presence of a small magnetic field yields a field-dependent Hill’s equation which predicts that the major effect of such a field is to reduce the widths of the instability regions. Experimental measurements on Nb-NbxOy-Pb junctions of intermediate length, performed at different operating temperatures in order to vary the junction parameters and for various magnetic field values, verify the physical existence of switching from the MCB to the ZFS’s. Good qualitative, and in many cases quantitative, agreement between analytic, numerical, and experimental results is obtained

Superconductivity enhanced conductance fluctuations in few layer graphene nanoribbons

We investigate the mesoscopic disorder induced rms conductance variance $\delta G$ in a few layer graphene nanoribbon (FGNR) contacted by two superconducting (S) Ti/Al contacts. By sweeping the back-gate voltage, we observe pronounced conductance fluctuations superimposed on a linear background of the two terminal conductance G. The linear gate-voltage induced response can be modeled by a set of inter-layer and intra-layer capacitances. $\delta G$ depends on temperature T and source-drain voltage $V_{sd}$. $\delta G$ increases with decreasing T and $|V_{sd}|$. When lowering $|V_{sd}|$, a pronounced cross-over at a voltage corresponding to the superconducting energy gap $\Delta$ is observed. For |V_{sd}|\ltequiv \Delta the fluctuations are markedly enhanced. Expressed in the conductance variance $G_{GS}$ of one graphene-superconducutor (G-S) interface, values of 0.58 e^2/h are obtained at the base temperature of 230 mK. The conductance variance in the sub-gap region are larger by up to a factor of 1.4-1.8 compared to the normal state. The observed strong enhancement is due to phase coherent charge transfer caused by Andreev reflection at the nanoribbon-superconductor interface.Comment: 15 pages, 5 figure

Regulation of releasable vesicle pool sizes by protein kinase A-dependent phosphorylation of SNAP-25

AbstractProtein kinase A (PKA) is a key regulator of neurosecretion, but the molecular targets remain elusive. We combined pharmacological manipulations of kinase and phosphatase activities with mutational studies on the exocytotic machinery driving fusion of catecholamine-containing vesicles from chromaffin cells. We found that constitutive PKA activity was necessary to maintain a large number of vesicles in the release-ready, so-called primed, state, whereas calcineurin (protein phosphatase 2B) activity antagonized this effect. Overexpression of the SNARE protein SNAP-25a mutated in a PKA phosphorylation site (Thr-138) eliminated the effect of PKA inhibitors on the vesicle priming process. Another, unidentified, PKA target regulated the relative size of two different primed vesicle pools that are distinguished by their release kinetics. Overexpression of the SNAP-25b isoform increased the size of both primed vesicle pools by a factor of two, and mutations in the conserved Thr-138 site had similar effects as in the a isoform

Basic Surgical Techniques in the Göttingen Minipig: Intubation, Bladder Catheterization, Femoral Vessel Catheterization, and Transcardial Perfusion

The emergence of the Göttingen minipig in research of topics such as neuroscience, toxicology, diabetes, obesity, and experimental surgery reflects the close resemblance of these animals to human anatomy and physiology 1-6.The size of the Göttingen minipig permits the use of surgical equipment and advanced imaging modalities similar to those used in humans 6-8. The aim of this instructional video is to increase the awareness on the value of minipigs in biomedical research, by demonstrating how to perform tracheal intubation, transurethral bladder catheterization, femoral artery and vein catheterization, as well as transcardial perfusion

Isotope Effect in the Presence of Magnetic and Nonmagnetic Impurities

The effect of impurities on the isotope coefficient is studied theoretically in the framework of Abrikosov-Gor'kov approach generalized to account for both potential and spin-flip scattering in anisotropic superconductors. An expression for the isotope coefficient as a function of the critical temperature is obtained for a superconductor with an arbitrary contribution of spin-flip processes to the total scattering rate and an arbitrary degree of anisotropy of the superconducting order parameter, ranging from isotropic s-wave to d-wave and including anisotropic s-wave and mixed (s+d)-wave as particular cases. It is found that both magnetic and nonmagnetic impurities enhance the isotope coefficient, the enhancement due to magnetic impurities being generally greater than that due to nonmagnetic impurities. From the analysis of the experimental results on La-Sr-Cu-M-O high temperature superconductor, it is concluded that the symmetry of the pairing state in this system differs from a pure d-wave.Comment: 4 pages, 3 figure