The conduction pathway of potassium channels is water free under physiological conditions.

Ion conduction through potassium channels is a fundamental process of life. On the basis of crystallographic data, it was originally proposed that potassium ions and water molecules are transported through the selectivity filter in an alternating arrangement, suggesting a "water-mediated" knock-on mechanism. Later on, this view was challenged by results from molecular dynamics simulations that revealed a "direct" knock-on mechanism where ions are in direct contact. Using solid-state nuclear magnetic resonance techniques tailored to characterize the interaction between water molecules and the ion channel, we show here that the selectivity filter of a potassium channel is free of water under physiological conditions. Our results are fully consistent with the direct knock-on mechanism of ion conduction but contradict the previously proposed water-mediated knock-on mechanism

GluR1 links structural and functional plasticity at excitatory synapses

Long-term potentiation (LTP), a cellular model of learning and memory, produces both an enhancement of synaptic function and an increase in the size of the associated dendritic spine. Synaptic insertion of AMPA receptors is known to play an important role in mediating the increase in synaptic strength during LTP, whereas the role of AMPA receptor trafficking in structural changes remains unexplored. Here, we examine how the cell maintains the correlation between spine size and synapse strength during LTP. We found that cells exploit an elegant solution by linking both processes to a single molecule: the AMPA-type glutamate receptor subunit 1 (GluR1). Synaptic insertion of GluR1 is required to permit a stable increase in spine size, both in hippocampal slice cultures and in vivo. Synaptic insertion of GluR1 is not sufficient to drive structural plasticity. Although crucial to the expression of LTP, the ion channel function of GluR1 is not required for the LTP-driven spine size enhancement. Remarkably, a recombinant cytosolic C-terminal fragment (C-tail) of GluR1 is driven to the postsynaptic density after an LTP stimulus, and the synaptic incorporation of this isolated GluR1 C-tail is sufficient to permit spine enlargement even when postsynaptic exocytosis of endogenous GluR1 is blocked. We conclude that during plasticity, synaptic insertion of GluR1 has two functions: the established role of increasing synaptic strength via its ligand-gated ion channel, and a novel role through the structurally stabilizing effect of its C terminus that permits an increase in spine size

Glutamate receptor exocytosis and spine enlargement during chemically induced long-term potentiation

The changes in synaptic morphology and receptor content that underlie neural plasticity are poorly understood. Here, we use a pH-sensitive green fluorescent protein to tag recombinant glutamate receptors and monitor their dynamics onto dendritic spine surfaces. We show that chemically induced long-term potentiation (chemLTP) drives robust exocytosis of AMPA receptors. In contrast, the same stimulus produces a small reduction of NMDA receptors from the spine surface. chemLTP produces similar modification of small and large spines. Interestingly, during chemLTP induction, spines increase in volume before accumulation of AMPA receptors on their surface, indicating that distinct mechanisms underlie changes in morphology and receptor content

A robust automated method to analyze rodent motion during fear conditioning

A central question in the study of LTP has been to determine what role it plays in memory formation and storage. One valuable form of learning for addressing this issue is associative fear conditioning. In this paradigm an animal learns to associate a tone and shock, such that subsequent presentation of a tone evokes a fear response (freezing behavior). Recent studies indicate that overlapping cellular processes underlie fear conditioning and LTP. The fear response has generally been scored manually which is both labor-intensive and subject to potential artifacts such as inconsistent or biased results. Here we describe a simple automated method that provides unbiased and rapid analysis of animal motion. We show that measured motion, in units termed significant motion pixels (SMPs), is both linear and robust over a wide range of animal speeds and detection thresholds and scores freezing in a quantitatively similar manner to trained human observers. By comparing the frequency distribution of motion during baseline periods and to the response to fox urine (which causes unconditioned fear), we suggest that freezing and non-freezing are distinct behaviors. Finally, we show how this algorithm can be applied to a fear conditioning paradigm yielding information on long and short-term associative memory as well as habituation. This automated analysis of fear conditioning will permit a more rapid and accurate assessment of the role of LTP in memory

Analysis of time-profiles with in-beam PET monitoring in charged particle therapy

Background: Treatment verification with PET imaging in charged particle therapy is conventionally done by comparing measurements of spatial distributions with Monte Carlo (MC) predictions. However, decay curves can provide additional independent information about the treatment and the irradiated tissue. Most studies performed so far focus on long time intervals. Here we investigate the reliability of MC predictions of space and time (decay rate) profiles shortly after irradiation, and we show how the decay rates can give an indication about the elements of which the phantom is made up. Methods and Materials: Various phantoms were irradiated in clinical and near-clinical conditions at the Cyclotron Centre of the Bronowice proton therapy centre. PET data were acquired with a planar 16x16 cm$^2$ PET system. MC simulations of particle interactions and photon propagation in the phantoms were performed using the FLUKA code. The analysis included a comparison between experimental data and MC simulations of space and time profiles, as well as a fitting procedure to obtain the various isotope contributions in the phantoms. Results and conclusions: There was a good agreement between data and MC predictions in 1-dimensional space and decay rate distributions. The fractions of $^{11}$C, $^{15}$O and $^{10}$C that were obtained by fitting the decay rates with multiple simple exponentials generally agreed well with the MC expectations. We found a small excess of $^{10}$C in data compared to what was predicted in MC, which was clear especially in the PE phantom.Comment: 9 pages, 5 figures, 1 table. Proceedings of the 20th International Workshop on Radiation Imaging Detectors (iWorid2018), 24-28 June 2018, Sundsvall, Swede

Temperature-doping phase diagram of layered superconductors

The superconducting properties of a layered system are analyzed for the cases of zero- and non-zero angular momentum of the pairs. The effective thermodynamic potential for the quasi-2D XY-model for the gradients of the phase of the order parameter is derived from the microscopic superconducting Hamiltonian. The dependence of the superconducting critical temperature T_c on doping, or carrier density, is studied at different values of coupling and inter-layer hopping. It is shown that the critical temperature T_c of the layered system can be lower than the critical temperature of the two-dimensional Berezinskii-Kosterlitz-Thouless transition T_BKT at some values of the model parameters, contrary to the case when the parameters of the XY-model do not depend on the microscopic Hamiltonian parameters.Comment: To be published in Phys. Rev.

Time reparametrization group and the long time behaviour in quantum glassy systems

We study the long time dynamics of a quantum version of the Sherrington-Kirkpatrick model. Time reparametrizations of the dynamical equations have a parallel with renormalization group transformations, and within this language the long time behaviour of this model is controlled by a reparametrization group (R$_p$G) fixed point of the classical dynamics. The irrelevance of the quantum terms in the dynamical equations in the aging regime explains the classical nature of the violation of the fluctuation-dissipation theorem.Comment: 4 page

Interaction-induced Bose Metal in 2D

We show here that the regularization of the conductivity resulting from the bosonic interactions on the `insulating' (quantum disordered) side of an insulator-superconductor transition in 2D gives rise to a metal with a finite conductivity, $\sigma =(2/\pi) 4 e^2/h$, as temperature tends to zero. The Bose metal is stable to weak disorder and hence represents a concrete example of an interaction-induced metallic phase. Phenomenological inclusion of dissipation reinstates the anticipated insulating behaviour in the quantum-disordered regime. Hence, we conclude that the traditionally-studied insulator-superconductor transition, which is driven solely by quantum fluctuations, corresponds to a superconductor-metal transition. The possible relationship to experiments on superconducting thin films in which a low-temperature metallic phase has been observed is discussed.Comment: A figure has been added and the physics has been clarified. To appear in PR

Monitoring Proton Therapy Through In-Beam PET: An Experimental Phantom Study

In this paper, we investigate the use of a positron emission tomography (PET) system to monitor the proton therapy. The monitoring procedure is based on the comparison between the β+ activity generated in the irradiated volume during the treatment, with the β+ activity distribution obtained with Monte Carlo (MC) simulation. The dedicated PET system is a dual head detection system; each head is composed of nine scintillating LYSO crystal matrices read out independently with a custom modularized acquisition system. Our experimental data were acquired at the Cyclotron Centre Bronowice, Institute Nuclear Physics in Kraków, Poland, and were simulated with the FLUKA MC code. Homogeneous and heterogeneous plastic phantoms were irradiated with monoenergetic 130 MeV protons. The capabilities of our PET system to distinguish different irradiated materials were investigated, and the proton pencil-beams were used as probes. Our focus was to analyze the activity width and the total activity event number in several cases. Irradiations were performed using either single pencil-beams one at a time, or two pencil-beams during the same data taking. The comparison of 1-D activity profile for experimental data and MC simulation were always in good agreement showing that, the treatment quality assessment in proton therapy can be based on β+ activity measurements