The autophagic response to Staphylococcus aureus provides an intracellular niche in neutrophils

Staphylococcus aureus is a major human pathogen causing multiple pathologies, from cutaneous lesions to life-threatening sepsis. Although neutrophils contribute to immunity against S. aureus, multiple lines of evidence suggest that these phagocytes can provide an intracellular niche for staphylococcal dissemination. However, the mechanism of neutrophil subversion by intracellular S. aureus remains unknown. Targeting of intracellular pathogens by macroautophagy/autophagy is recognized as an important component of host innate immunity, but whether autophagy is beneficial or detrimental to S. aureus-infected hosts remains controversial. Here, using larval zebrafish, we showed that the autophagy marker Lc3 rapidly decorates S. aureus following engulfment by macrophages and neutrophils. Upon phagocytosis by neutrophils, Lc3-positive, non-acidified spacious phagosomes are formed. This response is dependent on phagocyte NADPH oxidase as both cyba/p22phox knockdown and diphenyleneiodonium (DPI) treatment inhibited Lc3 decoration of phagosomes. Importantly, NADPH oxidase inhibition diverted neutrophil S. aureus processing into tight acidified vesicles, which resulted in increased host resistance to the infection. Some intracellular bacteria within neutrophils were also tagged by Sqstm1/p62-GFP fusion protein and loss of Sqstm1 impaired host defense. Together, we have shown that intracellular handling of S. aureus by neutrophils is best explained by Lc3-associated phagocytosis (LAP), which appears to provide an intracellular niche for bacterial pathogenesis, while the selective autophagy receptor Sqstm1 is host-protective. The antagonistic roles of LAP and Sqstm1-mediated pathways in S. aureus-infected neutrophils may explain the conflicting reports relating to anti-staphylococcal autophagy and provide new insights for therapeutic strategies against antimicrobial-resistant Staphylococci

Investigation into individual health and exposure to infectious agents of platypuses (Ornithorhynchus anatinus) in two river catchments in northwest Tasmania

Changes in the health of individuals within wildlife populations can be a cause or effect of population declines in wildlife species. Aspects of individual platypus (Ornithorhynchus anatinus) health have been reported. However, holistic studies investigating potential synergistic effects of both pathogens and environmental factors are needed to expand understanding of platypus individual health. We collected baseline data on the health of platypuses in two Tasmanian river catchments (including evidence of the potentially fatal fungal disease mucormycosis) and on individual, demographic, and geographic patterns associated with health data results. We examined 130 wild platypuses from the Inglis River Catchment and 24 platypuses from the Seabrook Creek Catchment in northwest Tasmania between 29 August 2011 and 31 August 2013. More than 90% of captured platypuses were infected with ticks, Theileria spp., and trypanosomes. Evidence of exposure to other infections, including Salmonella spp., Leptospira spp., and intestinal parasites, was low (<10%). Three platypuses had single fungal granulomas in the webbing of a forefoot, but no evidence of mucormycosis was found in any of the study animals. Possible subclinical hepatopathies or cholangiohepatopathies were found in six platypuses. Exposure to infectious agents did not cluster geographically, demographically, or in individuals, and there was minimal evidence of morbidity resulting from infection. This study has provided important baseline data for monitoring the effects of threatening processes, including mucormycosis, on the health of infected populations

Aging and Immortality in a Cell Proliferation Model

We investigate a model of cell division in which the length of telomeres within the cell regulate their proliferative potential. At each cell division the ends of linear chromosomes change and a cell becomes senescent when one or more of its telomeres become shorter than a critical length. In addition to this systematic shortening, exchange of telomere DNA between the two daughter cells can occur at each cell division. We map this telomere dynamics onto a biased branching diffusion process with an absorbing boundary condition whenever any telomere reaches the critical length. As the relative effects of telomere shortening and cell division are varied, there is a phase transition between finite lifetime and infinite proliferation of the cell population. Using simple first-passage ideas, we quantify the nature of this transition.Comment: 6 pages, 1 figure, 2-column revtex4 format; version 2: final published form; contains various improvements in response to referee comment

The staggered domain wall fermion method

A different lattice fermion method is introduced. Staggered domain wall fermions are defined in 2n+1 dimensions and describe 2^n flavors of light lattice fermions with exact U(1) x U(1) chiral symmetry in 2n dimensions. As the size of the extra dimension becomes large, 2^n chiral flavors with the same chiral charge are expected to be localized on each boundary and the full SU(2^n) x SU(2^n) flavor chiral symmetry is expected to be recovered. SDWF give a different perspective into the inherent flavor mixing of lattice fermions and by design present an advantage for numerical simulations of lattice QCD thermodynamics. The chiral and topological index properties of the SDWF Dirac operator are investigated. And, there is a surprise ending...Comment: revtex4, 7 figures, minor revisions, 2 references adde

Tracer Tests in a Fractured Dolomite: 3. Analysis of Mass Transfer in Single-Well Injection-Withdrawal Tests

We investigated multiple-rate diffusion as a possible explanation for observed behavior in a suite of single-well injection-withdrawal (SWIW) tests conducted in a fractured dolomite. We first investigated the ability of a conventional double-porosity model and a multirate diffusion model to explain the data. This revealed that the multirate diffusion hypothesis/model is most consistent with all available data, and is the only model to date that is capable of matching each of the recovery curves entirely. Second, we studied the sensitivity of the SWIW recovery curves to the distribution of diffusion rate coefficients and other parameters. We concluded that the SWIW test is very sensitive to the distribution of rate coefficients, but is relatively insensitive to other flow and transport parameters such as advective porosity and dispersivity. Third, we examined the significance of the constant double-log late-time slopes ({minus}2. 1 to {minus}2.8), which are present in several data sets. The observed late-time slopes are significantly different than would be predicted by either conventional double-porosity or single-porosity media, and are found to be a distinctive feature of multirate diffusion under SWIW test conditions. Fourth, we found that the estimated distributions of diffusion rate coefficients are very broad, with the distributions spanning a range of at least 3.6 to 5.7 orders of magnitude

Rotational and Vibrational Dynamics of Interstitial Molecular Hydrogen

The calculation of the hindered roton-phonon energy levels of a hydrogen molecule in a confining potential with different symmetries is systematized for the case when the rotational angular momentum $J$ is a good quantum number. One goal of this program is to interpret the energy-resolved neutron time of flight spectrum previously obtained for H$_{2}$C$_{60}$. This spectrum gives direct information on the energy level spectrum of H$_2$ molecules confined to the octahedral interstitial sites of solid C$_{60}$. We treat this problem of coupled translational and orientational degrees of freedom a) by construction of an effective Hamiltonian to describe the splitting of the manifold of states characterized by a given value of $J$ and having a fixed total number of phonon excitations, b) by numerical solutions of the coupled translation-rotation problem on a discrete mesh of points in position space, and c) by a group theoretical symmetry analysis. Results obtained from these three different approaches are mutually consistent. The results of our calculations explain several hitherto uninterpreted aspects of the experimental observations, but show that a truly satisfactory orientational potential for the interaction of an H$_2$ molecule with a surrounding array of C atoms has not yet been developed.Comment: 53 pages, 9 figures, to appear in Phys. Rev B (in press). Phys. Rev. B (in press

Improvements in obtaining and characterizing mouse cerebrospinal fluid. Application to mouse hepatitis virus-induced encephalomyelitis

This report describes advances in techniques for analyzing cellular and humoral immune components in the cerebrospinal fluid (CSF) of the mouse that are applicable to other laboratory animals. CSF studies undertaken during experimental infection of mice with JHM strain virus (JHMV) of mouse hepatitis virus are presented. A critical pitfall which can lead to erroneous or invalid results is contamination of the CSF by even minute quantities of blood. Means of avoiding this contamination are attention to anatomical reference points, the use of a micropipet, and prior intracardiac perfusion of animals with phosphate-buffered saline. Cells in the CSF were typed as either B, T, polymorphonuclear, or mononuclear cells by the combination of a microcytotoxicity assay and histologic stains. A radioimmunoassay (RIA) allowed quantification of antibodies to JHMV in the CSF and indicated the presence of intrathecal synthesis of antibody in chronically infected mice. The combined use of these sensitive methods makes possible CSF analysis in individual mice rather than in pooled groups

Time and Frequency Domain Identification and Analysis of a Gas Turbine Engine

The NARMAX (Nonlinear Auto Regressive Moving Average model with eXogenous inputs) approach has been used to analyse the dynamics of a gas turbine engine. The fuel flow-shaft speed relationship is analysed by identifying both time and frequency domain models of the system. The frequency domain analysis is studied by mapping the discrete-time NARMAX models into the Generalised Frequency Response Functions (GFRF's) to reveal the nonlinear coupling between the various input spectral components and the energy transfer mechanisms in the system. A continuous-time nonlinear differential equation model is also estimated using the Generalised Frequency Response Functions

Magnetic fields in protoplanetary disks

Magnetic fields likely play a key role in the dynamics and evolution of protoplanetary discs. They have the potential to efficiently transport angular momentum by MHD turbulence or via the magnetocentrifugal acceleration of outflows from the disk surface, and magnetically-driven mixing has implications for disk chemistry and evolution of the grain population. However, the weak ionisation of protoplanetary discs means that magnetic fields may not be able to effectively couple to the matter. I present calculations of the ionisation equilibrium and magnetic diffusivity as a function of height from the disk midplane at radii of 1 and 5 AU. Dust grains tend to suppress magnetic coupling by soaking up electrons and ions from the gas phase and reducing the conductivity of the gas by many orders of magnitude. However, once grains have grown to a few microns in size their effect starts to wane and magnetic fields can begin to couple to the gas even at the disk midplane. Because ions are generally decoupled from the magnetic field by neutral collisions while electrons are not, the Hall effect tends to dominate the diffusion of the magnetic field when it is able to partially couple to the gas. For a standard population of 0.1 micron grains the active surface layers have a combined column of about 2 g/cm^2 at 1 AU; by the time grains have aggregated to 3 microns the active surface density is 80 g/cm^2. In the absence of grains, x-rays maintain magnetic coupling to 10% of the disk material at 1 AU (150 g/cm^2). At 5 AU the entire disk thickness becomes active once grains have aggregated to 1 micron in size.Comment: 11 pages, 11 figs, aastex.cls. Accepted for publication in Astrophysics & Space Science. v3 corrects bibliograph

Normal-state conductivity in underdoped La_{2-x}Sr_xCuO_4 thin films: Search for nonlinear effects related to collective stripe motion

We report a detailed study of the electric-field dependence of the normal-state conductivity in La_{2-x}Sr_xCuO_4 thin films for two concentrations of doped holes, x=0.01 and 0.06, where formation of diagonal and vertical charged stripes was recently suggested. In order to elucidate whether high electric fields are capable of depinning the charged stripes and inducing their collective motion, we have measured current-voltage characteristics for various orientations of the electric field with respect to the crystallographic axes. However, even for the highest possible fields (~1000 V/cm for x=0.01 and \~300 V/cm for x=0.06) we observed no non-linear-conductivity features except for those related to the conventional Joule heating of the films. Our analysis indicates that Joule heating, rather than collective electron motion, may also be responsible for the non-linear conductivity observed in some other 2D transition-metal oxides as well. We discuss that a possible reason why moderate electric fields fail to induce a collective stripe motion in layered oxides is that fairly flexible and compressible charged stripes can adjust themselves to the crystal lattice and individual impurities, which makes their pinning much stronger than in the case of conventional rigid charge-density waves.Comment: 10 pages, 10 figures, accepted for publication in Phys. Rev.