Cellular excitability and the regulation of functional neuronal identity: from gene expression to neuromodulation

The intrinsic properties of a neuron determine the translation of synaptic input to axonal output. It is this input– output relationship that is the heart of all nervous system activity. As such, the overall regulation of the intrinsic excitability of a neuron directly determines the output of that neuron at a given point in time, giving the cell a unique “functional identity.” To maintain this distinct functional output, neurons must adapt to changing patterns of synaptic excitation. These adaptations are essential to prevent neurons from either falling silent as synaptic excitation falls or becoming saturated as excitation increases. In the absence of stabilizing mechanisms, activity-dependent plasticity could drive neural activity to saturation or quiescence. Furthermore, as cells adapt to changing patterns of synaptic input, presumably the overall balance of intrinsic conductances of the cell must be maintained so that reliable output is achieved (Daoudal and Debanne, 2003; Turrigiano and Nelson, 2004; Frick and Johnston, 2005). Although these regulatory phenomena have been well documented, the molecular and physiological mechanisms involved are poorly understood

Development and validation of a chemostat gut model to study both planktonic and biofilm modes of growth of Clostridium difficile and human microbiota

Copyright: 2014 Crowther et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.The human gastrointestinal tract harbours a complex microbial community which exist in planktonic and sessile form. The degree to which composition and function of faecal and mucosal microbiota differ remains unclear. We describe the development and characterisation of an in vitro human gut model, which can be used to facilitate the formation and longitudinal analysis of mature mixed species biofilms. This enables the investigation of the role of biofilms in Clostridium difficile infection (CDI). A well established and validated human gut model of simulated CDI was adapted to incorporate glass rods that create a solid-gaseous-liquid interface for biofilm formation. The continuous chemostat model was inoculated with a pooled human faecal emulsion and controlled to mimic colonic conditions in vivo. Planktonic and sessile bacterial populations were enumerated for up to 46 days. Biofilm consistently formed macroscopic structures on all glass rods over extended periods of time, providing a framework to sample and analyse biofilm structures independently. Whilst variation in biofilm biomass is evident between rods, populations of sessile bacterial groups (log10 cfu/g of biofilm) remain relatively consistent between rods at each sampling point. All bacterial groups enumerated within the planktonic communities were also present within biofilm structures. The planktonic mode of growth of C. difficile and gut microbiota closely reflected observations within the original gut model. However, distinct differences were observed in the behaviour of sessile and planktonic C. difficile populations, with C. difficile spores preferentially persisting within biofilm structures. The redesigned biofilm chemostat model has been validated for reproducible and consistent formation of mixed species intestinal biofilms. This model can be utilised for the analysis of sessile mixed species communities longitudinally, potentially providing information of the role of biofilms in CDI.Peer reviewe

Nodeless superconductivity in the noncentrosymmetric Mo3_3Rh2_2N superconductor: a μ\muSR study

The noncentrosymmetric superconductor Mo$_3$Rh$_2$N, with $T_c = 4.6$ K, adopts a $\beta$-Mn-type structure (space group $P$4$_1$32), similar to that of Mo$_3$Al$_2$C. Its bulk superconductivity was characterized by magnetization and heat-capacity measurements, while its microscopic electronic properties were investigated by means of muon-spin rotation and relaxation ($\mu$SR). The low-temperature superfluid density, measured via transverse-field (TF)-$\mu$SR, evidences a fully-gapped superconducting state with $\Delta_0 = 1.73 k_\mathrm{B}T_c$, very close to 1.76 $k_\mathrm{B}T_c$ - the BCS gap value for the weak coupling case, and a magnetic penetration depth $\lambda_0 = 586$ nm. The absence of spontaneous magnetic fields below the onset of superconductivity, as determined by zero-field (ZF)-$\mu$SR measurements, hints at a preserved time-reversal symmetry in the superconducting state. Both TF-and ZF-$\mu$SR results evidence a spin-singlet pairing in Mo$_3$Rh$_2$N.Comment: 5 figures and 5 pages. Accepted for publication as a Rapid Communication in Phys. Rev.

Automatic estimation of flux distributions of astrophysical source populations

In astrophysics a common goal is to infer the flux distribution of populations of scientifically interesting objects such as pulsars or supernovae. In practice, inference for the flux distribution is often conducted using the cumulative distribution of the number of sources detected at a given sensitivity. The resulting "$\log(N>S)$-$\log (S)$" relationship can be used to compare and evaluate theoretical models for source populations and their evolution. Under restrictive assumptions the relationship should be linear. In practice, however, when simple theoretical models fail, it is common for astrophysicists to use prespecified piecewise linear models. This paper proposes a methodology for estimating both the number and locations of "breakpoints" in astrophysical source populations that extends beyond existing work in this field. An important component of the proposed methodology is a new interwoven EM algorithm that computes parameter estimates. It is shown that in simple settings such estimates are asymptotically consistent despite the complex nature of the parameter space. Through simulation studies it is demonstrated that the proposed methodology is capable of accurately detecting structural breaks in a variety of parameter configurations. This paper concludes with an application of our methodology to the Chandra Deep Field North (CDFN) data set.Comment: Published in at http://dx.doi.org/10.1214/14-AOAS750 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Constrained by managerialism : caring as participation in the voluntary social services

The data in this study show that care is a connective process, underlying and motivating participation and as a force that compels involvement in the lives of others, care is at least a micro-participative process. Care or affinity not only persisted in the face of opposition, but it was also used by workers as a counter discourse and set of practices with which to resist the erosion of worker participation and open up less autonomized practices and ways of connecting with fellow staff, clients and the communities they served. The data suggest that while managerialism and taylorised practice models may remove or reduce opportunities for worker participation, care is a theme or storyline that gave workers other ways to understand their work and why they did it, as well as ways they were prepared to resist managerial priorities and directives, including the erosion of various kinds of direct and indirect participation. The degree of resistance possible, even in the highly technocratic worksite in Australia, shows that cracks and fissures exist within managerialism

Quantum Coherence at Low Temperatures in Mesoscopic Systems: Effect of Disorder

We study the disorder dependence of the phase coherence time of quasi one-dimensional wires and two-dimensional (2D) Hall bars fabricated from a high mobility GaAs/AlGaAs heterostructure. Using an original ion implantation technique, we can tune the intrinsic disorder felt by the 2D electron gas and continuously vary the system from the semi-ballistic regime to the localized one. In the diffusive regime, the phase coherence time follows a power law as a function of diffusion coefficient as expected in the Fermi liquid theory, without any sign of low temperature saturation. Surprisingly, in the semi-ballistic regime, it becomes independent of the diffusion coefficient. In the strongly localized regime we find a diverging phase coherence time with decreasing temperature, however, with a smaller exponent compared to the weakly localized regime.Comment: 21 pages, 30 figure

Cassini atmospheric chemistry mapper. Volume 1. Investigation and technical plan

The Cassini Atmospheric Chemistry Mapper (ACM) enables a broad range of atmospheric science investigations for Saturn and Titan by providing high spectral and spatial resolution mapping and occultation capabilities at 3 and 5 microns. ACM can directly address the major atmospheric science objectives for Saturn and for Titan, as defined by the Announcement of Opportunity, with pivotal diagnostic measurements not accessible to any other proposed Cassini instrument. ACM determines mixing ratios for atmospheric molecules from spectral line profiles for an important and extensive volume of the atmosphere of Saturn (and Jupiter). Spatial and vertical profiles of disequilibrium species abundances define Saturn's deep atmosphere, its chemistry, and its vertical transport phenomena. ACM spectral maps provide a unique means to interpret atmospheric conditions in the deep (approximately 1000 bar) atmosphere of Saturn. Deep chemistry and vertical transport is inferred from the vertical and horizontal distribution of a series of disequilibrium species. Solar occultations provide a method to bridge the altitude range in Saturn's (and Titan's) atmosphere that is not accessible to radio science, thermal infrared, and UV spectroscopy with temperature measurements to plus or minus 2K from the analysis of molecular line ratios and to attain an high sensitivity for low-abundance chemical species in the very large column densities that may be achieved during occultations for Saturn. For Titan, ACM solar occultations yield very well resolved (1/6 scale height) vertical mixing ratios column abundances for atmospheric molecular constituents. Occultations also provide for detecting abundant species very high in the upper atmosphere, while at greater depths, detecting the isotopes of C and O, constraining the production mechanisms, and/or sources for the above species. ACM measures the vertical and horizontal distribution of aerosols via their opacity at 3 microns and, particularly, at 5 microns. ACM recovers spatially-resolved atmospheric temperatures in Titan's troposphere via 3- and 5-microns spectral transitions. Together, the mixing ratio profiles and the aerosol distributions are utilized to investigate the photochemistry of the stratosphere and consequent formation processes for aerosols. Finally, ring opacities, observed during solar occultations and in reflected sunlight, provide a measurement of the particle size and distribution of ring material. ACM will be the first high spectral resolution mapping spectrometer on an outer planet mission for atmospheric studies while retaining a high resolution spatial mapping capability. ACM, thus, opens an entirely new range of orbital scientific studies of the origin, physio-chemical evolution and structure of the Saturn and Titan atmospheres. ACM provides high angular resolution spectral maps, viewing nadir and near-limb thermal radiation and reflected sunlight; sounds planetary limbs, spatially resolving vertical profiles to several atmospheric scale heights; and measures solar occultations, mapping both atmospheres and rings. ACM's high spectral and spatial resolution mapping capability is achieved with a simplified Fourier Transform spectrometer with a no-moving parts, physically compact design. ACM's simplicity guarantees an inherent stability essential for reliable performance throughout the lengthy Cassini Orbiter mission

Transport through side-coupled double quantum dots: from weak to strong interdot coupling

We report low-temperature transport measurements through a double quantum dot device in a configuration where one of the quantum dots is coupled directly to the source and drain electrodes, and a second (side-coupled) quantum dot interacts electrostatically and via tunneling to the first one. As the interdot coupling increases, a crossover from weak to strong interdot tunneling is observed in the charge stability diagrams that present a complex pattern with mergings and apparent crossings of Coulomb blockade peaks. While the weak coupling regime can be understood by considering a single level on each dot, in the intermediate and strong coupling regimes, the multi-level nature of the quantum dots needs to be taken into account. Surprisingly, both in the strong and weak coupling regimes, the double quantum dot states are mainly localized on each dot for most values of the parameters. Only in an intermediate coupling regime the device presents a single dot-like molecular behavior as the molecular wavefunctions weight is evenly distributed between the quantum dots. At temperatures larger than the interdot coupling energy scale, a loss of coherence of the molecular states is observed.Comment: 9 pages, 5 figure