Mutant huntingtin enhances activation of dendritic Kv4 K+ channels in striatal spiny projection neurons

Huntington\u27s disease (HD) is initially characterized by an inability to suppress unwanted movements, a deficit attributable to impaired synaptic activation of striatal indirect pathway spiny projection neurons (iSPNs). To better understand the mechanisms underlying this deficit, striatal neurons in ex vivo brain slices from mouse genetic models of HD were studied using electrophysiological, optical and biochemical approaches. Distal dendrites of iSPNs from symptomatic HD mice were hypoexcitable, a change that was attributable to increased association of dendritic Kv4 potassium channels with auxiliary KChIP subunits. This association was negatively modulated by TrkB receptor signaling. Dendritic excitability of HD iSPNs was rescued by knocking-down expression of Kv4 channels, by disrupting KChIP binding, by restoring TrkB receptor signaling or by lowering mutant-Htt (mHtt) levels with a zinc finger protein. Collectively, these studies demonstrate that mHtt induces reversible alterations in the dendritic excitability of iSPNs that could contribute to the motor symptoms of HD

Coherent c-axis transport in the underdoped cuprate superconductor YBCO

The electrical resistivity rho_c of the underdoped cuprate superconductor YBCO was measured perpendicular to the CuO_2 planes on ultra-high quality single crystals in magnetic fields large enough to suppress superconductivity. The incoherent insulating-like behavior of rho_c at high temperature, characteristic of all underdoped cuprates, is found to cross over to a coherent regime of metallic behavior at low temperature. This crossover coincides with the emergence of the small electron pocket detected in the Fermi surface of YBCO via quantum oscillations, the Hall and Seebeck coefficients and with the detection of a unidirectional modulation of the charge density as seen by high-field NMR measurements. The low coherence temperature is quantitatively consistent with the small hopping integral t_perp inferred from the splitting of the quantum oscillation frequencies. We conclude that the Fermi-surface reconstruction in YBCO at dopings from p = 0.08 to at least p = 0.15, attributed to stripe order, produces a metallic state with 3D coherence deep in the underdoped regime.Comment: 7 pages, 7 figure

Axion quasiparticles for axion dark matter detection

It has been suggested that certain antiferromagnetic topological insulators contain axion quasiparticles (AQs), and that such materials could be used to detect axion dark matter (DM). The AQ is a longitudinal antiferromagnetic spin fluctuation coupled to the electromagnetic Chern-Simons term, which, in the presence of an applied magnetic field, leads to mass mixing between the AQ and the electric field. The electromagnetic boundary conditions and transmission and reflection coefficients are computed. A model for including losses into this system is presented, and the resulting linewidth is computed. It is shown how transmission spectroscopy can be used to measure the resonant frequencies and damping coefficients of the material, and demonstrate conclusively the existence of the AQ. The dispersion relation and boundary conditions permit resonant conversion of axion DM into THz photons in a material volume that is independent of the resonant frequency, which is tuneable via an applied magnetic field. A parameter study for axion DM detection is performed, computing boost amplitudes and bandwidths using realistic material properties including loss. The proposal could allow for detection of axion DM in the mass range between 1 and 10 meV using current and near future technology

Incorporating chemical signalling factors into cell-based models of growing epithelial tissues

In this paper we present a comprehensive computational framework within which the effects of chemical signalling factors on growing epithelial tissues can be studied. The method incorporates a vertex-based cell model, in conjunction with a solver for the governing chemical equations. The vertex model provides a natural mesh for the finite element method (FEM), with node movements determined by force laws. The arbitrary Lagrangian–Eulerian formulation is adopted to account for domain movement between iterations. The effects of cell proliferation and junctional rearrangements on the mesh are also examined. By implementing refinements of the mesh we show that the finite element (FE) approximation converges towards an accurate numerical solution. The potential utility of the system is demonstrated in the context of Decapentaplegic (Dpp), a morphogen which plays a crucial role in development of the Drosophila imaginal wing disc. Despite the presence of a Dpp gradient, growth is uniform across the wing disc. We make the growth rate of cells dependent on Dpp concentration and show that the number of proliferation events increases in regions of high concentration. This allows hypotheses regarding mechanisms of growth control to be rigorously tested. The method we describe may be adapted to a range of potential application areas, and to other cell-based models with designated node movements, to accurately probe the role of morphogens in epithelial tissues

Preserving the impossible: conservation of soft-sediment hominin footprint sites and strategies for three-dimensional digital data capture.

Human footprints provide some of the most publically emotive and tangible evidence of our ancestors. To the scientific community they provide evidence of stature, presence, behaviour and in the case of early hominins potential evidence with respect to the evolution of gait. While rare in the geological record the number of footprint sites has increased in recent years along with the analytical tools available for their study. Many of these sites are at risk from rapid erosion, including the Ileret footprints in northern Kenya which are second only in age to those at Laetoli (Tanzania). Unlithified, soft-sediment footprint sites such these pose a significant geoconservation challenge. In the first part of this paper conservation and preservation options are explored leading to the conclusion that to 'record and digitally rescue' provides the only viable approach. Key to such strategies is the increasing availability of three-dimensional data capture either via optical laser scanning and/or digital photogrammetry. Within the discipline there is a developing schism between those that favour one approach over the other and a requirement from geoconservationists and the scientific community for some form of objective appraisal of these alternatives is necessary. Consequently in the second part of this paper we evaluate these alternative approaches and the role they can play in a 'record and digitally rescue' conservation strategy. Using modern footprint data, digital models created via optical laser scanning are compared to those generated by state-of-the-art photogrammetry. Both methods give comparable although subtly different results. This data is evaluated alongside a review of field deployment issues to provide guidance to the community with respect to the factors which need to be considered in digital conservation of human/hominin footprints

A Unifying Model of Genome Evolution Under Parsimony

We present a data structure called a history graph that offers a practical basis for the analysis of genome evolution. It conceptually simplifies the study of parsimonious evolutionary histories by representing both substitutions and double cut and join (DCJ) rearrangements in the presence of duplications. The problem of constructing parsimonious history graphs thus subsumes related maximum parsimony problems in the fields of phylogenetic reconstruction and genome rearrangement. We show that tractable functions can be used to define upper and lower bounds on the minimum number of substitutions and DCJ rearrangements needed to explain any history graph. These bounds become tight for a special type of unambiguous history graph called an ancestral variation graph (AVG), which constrains in its combinatorial structure the number of operations required. We finally demonstrate that for a given history graph $G$, a finite set of AVGs describe all parsimonious interpretations of $G$, and this set can be explored with a few sampling moves.Comment: 52 pages, 24 figure

Mechanochemical preparation of ceria-zirconia catalysts for the total oxidation of propane and naphthalene Volatile Organic Compounds

A range of ceria-zirconia mixed metal oxide catalysts were synthesised by mechanochemical milling from nitrate precursors and tested for propane and naphthalene total oxidation. The mixed CeZrOx metal oxide catalysts were more active compared to pure CeO2 and ZrO2, with the Ce0.90Zr0.10Ox catalyst the most active for both propane and naphthalene total oxidation. Catalysts were characterised by XRD, TGA, Raman spectroscopy, BET surface area, XPS, TEM and SEM-EDX techniques. Formation of CeZrOx solid solutions were observed for Zr content ranging from 5 to 25%, and phase separated materials were observed for higher Zr content of 50%. The incorporation of Zr into the CeO2 lattice increased the surface area compared to pure CeO2 and ZrO2, with evidence of a surface enrichment of Zr when concentrations were compared to the bulk. Incorporation of Zr was found to increase the surface concentration of oxygen defects in the CeZrOx mixed metal oxides, the concentration of these defect on the catalysts follows a similar trend to the propane and naphthalene total oxidation activity: The increased presence of oxygen defects and reducibility are factors responsible for the enhanced total oxidation activity of the mixed metal oxide catalysts, and the mechanochemical method is an effective preparation route for these active catalysts