Effect of Stress on Viral–Bacterial Synergy in Bovine Respiratory Disease: Novel Mechanisms to Regulate Inflammation

The severity of bovine respiratory infections has been linked to a variety offactors, including environmental and nutritional changes, transportation, and socialreorganization of weaned calves. Fatal respiratory infections, however, usually occurwhen a primary viral infection compromises host defences and enhances the severityof a secondary bacterial infection. This viral–bacterial synergy can occur by a numberof different mechanisms and disease challenge models have been developed to analysehost responses during these respiratory infections. A primary bovine herpesvirus-1(BHV-1) respiratory infection followed by a secondary challenge with Mannheimia haemolyticaresults in fatal bovine respiratory disease (BRD) and host responses to these two pathogens have been studied extensively. We used this disease model todemonstrate that stress significantly altered the viral–bacterial synergy resulting infatal BRD. Functional genomic analysis revealed that BHV-1 infection enhanced toll-likereceptors (TLR) expression and increased pro-inflammatory responses whichcontribute to the severity of a Mannheimia haemolytica infection. TLRs play a criticalrole in detecting bacterial infections and inducing pro-inflammatory responses. It isdifficult to understand, however, how stress-induced corticosteroids could enhancethis form of viral–bacterial synergy. Nuclear translocation of the glucocorticoidreceptor activates cell signalling pathways which inhibit both TLR signallingand pro-inflammatory responses. The apparent conundrum between stress-inducedcorticosteroids and enhanced BRD susceptibility is discussed in terms of present data and previous investigations of stress and respiratory disease

On the analogy between streamlined magnetic and solid obstacles

Analogies are elaborated in the qualitative description of two systems: the magnetohydrodynamic (MHD) flow moving through a region where an external local magnetic field (magnetic obstacle) is applied, and the ordinary hydrodynamic flow around a solid obstacle. The former problem is of interest both practically and theoretically, and the latter one is a classical problem being well understood in ordinary hydrodynamics. The first analogy is the formation in the MHD flow of an impenetrable region -- core of the magnetic obstacle -- as the interaction parameter $N$, i.e. strength of the applied magnetic field, increases significantly. The core of the magnetic obstacle is streamlined both by the upstream flow and by the induced cross stream electric currents, like a foreign insulated insertion placed inside the ordinary hydrodynamic flow. In the core, closed streamlines of the mass flow resemble contour lines of electric potential, while closed streamlines of the electric current resemble contour lines of pressure. The second analogy is the breaking away of attached vortices from the recirculation pattern produced by the magnetic obstacle when the Reynolds number $Re$, i.e. velocity of the upstream flow, is larger than a critical value. This breaking away of vortices from the magnetic obstacle is similar to that occurring past a real solid obstacle. Depending on the inlet and/or initial conditions, the observed vortex shedding can be either symmetric or asymmetric.Comment: minor changes, accepted for PoF, 26 pages, 7 figure

Discrete exterior calculus (DEC) for the surface Navier-Stokes equation

We consider a numerical approach for the incompressible surface Navier-Stokes equation. The approach is based on the covariant form and uses discrete exterior calculus (DEC) in space and a semi-implicit discretization in time. The discretization is described in detail and related to finite difference schemes on staggered grids in flat space for which we demonstrate second order convergence. We compare computational results with a vorticity-stream function approach for surfaces with genus 0 and demonstrate the interplay between topology, geometry and flow properties. Our discretization also allows to handle harmonic vector fields, which we demonstrate on a torus.Comment: 21 pages, 9 figure

Numerical Computations with H(div)-Finite Elements for the Brinkman Problem

The H(div)-conforming approach for the Brinkman equation is studied numerically, verifying the theoretical a priori and a posteriori analysis in previous work of the authors. Furthermore, the results are extended to cover a non-constant permeability. A hybridization technique for the problem is presented, complete with a convergence analysis and numerical verification. Finally, the numerical convergence studies are complemented with numerical examples of applications to domain decomposition and adaptive mesh refinement.Comment: Minor clarifications, added references. Reordering of some figures. To appear in Computational Geosciences, final article available at http://www.springerlink.co

Advancing the defensive explanation for anxiety disorders: lorazepam effects on human defense are systematically modulated by personality and threat-type

Clinically effective drugs against human anxiety and fear systematically alter the innate defensive behavior of rodents, suggesting that in humans these emotions reflect defensive adaptations. Compelling experimental human evidence for this theory is yet to be obtained. We report the clearest test to date by investigating the effects of 1 and 2mg of the anti-anxiety drug lorazepam on the intensity of threat-avoidance behavior in 40 healthy adult volunteers (20 females). We found lorazepam modulated the intensity of participants’ threat-avoidance behavior in a dose-dependent manner. However, the pattern of effects depended upon two factors: type of threat-avoidance behavior and theoretically relevant measures of personality. In the case of flight behavior (one-way active avoidance), lorazepam increased intensity in low scorers on the Fear Survey Schedule tissuedamage fear but reduced it in high scorers. Conversely, in the case of risk-assessment behavior (two-way active avoidance), lorazepam reduced intensity in low scorers on the Spielberger trait anxiety but increased it in high scorers. Anti-anxiety drugs do not systematically affect rodent flight behavior; therefore, we interpret this new finding as suggesting that lorazepam has a broader effect on defense in humans than in rodents, perhaps by modulating general perceptions of threat intensity. The different patterning of lorazepam effects on the two behaviors implies that human perceptions of threat intensity are nevertheless distributed across two different neural streams, which influence effects observed on one-way or two-way active avoidance demanded by the situation

Pharmacological Alterations of Anxious Behaviour in Mice Depending on Both Strain and the Behavioural Situation

A previous study comparing non-emotive mice from the strain C57BL/6/ByJ with ABP/Le mice showed ABP/Le to be more anxious in an open-field situation. In the present study, several compounds affecting anxiety were assayed on ABP/Le and C57BL/6/ByJ mice using three behavioural models of anxiety: the elevated plus-maze, the light-dark discrimination test and the free exploratory paradigm. The compounds used were the full benzodiazepine receptor agonist, chlordiazepoxide, and the antagonist, flumazenil, the GABAA antagonist, bicuculline, the full 5-HT1A agonist 8-OH-DPAT, and the mixed 5-HT1A/5-HT1B agonist, RU 24969. Results showed the effect of the compounds to be dependent on both the strain and the behavioural task. Several compounds found to be anxiolytic in ABP/Le mice had an anxiogenic effect on C57BL/6/ByJ mice. More behavioural changes were observed for ABP/Le in the elevated plus-maze, but the clearest findings for C57BL/6/ByJ mice were observed in the light-dark discrimination apparatus. These data demonstrate that anxious behaviour is a complex phenomenon which cannot be described by a single behavioural task nor by the action of a single compound

An introduction to the Australian and New Zealand flux tower network - OzFlux

Published: 31 October 2016OzFlux is the regional Australian and New Zealand flux tower network that aims to provide a continental-scale national research facility to monitor and assess trends, and improve predictions, of Australia's terrestrial biosphere and climate. This paper describes the evolution, design, and current status of OzFlux as well as provides an overview of data processing. We analyse measurements from all sites within the Australian portion of the OzFlux network and two sites from New Zealand. The response of the Australian biomes to climate was largely consistent with global studies except that Australian systems had a lower ecosystem water-use efficiency. Australian semi-arid/arid ecosystems are important because of their huge extent (70 %) and they have evolved with common moisture limitations. We also found that Australian ecosystems had a similar radiation-use efficiency per unit leaf area compared to global values that indicates a convergence toward a similar biochemical efficiency. The two New Zealand sites represented extremes in productivity for a moist temperate climate zone, with the grazed dairy farm site having the highest GPP of any OzFlux site (2620 gC m⁻² yr⁻¹) and the natural raised peat bog site having a very low GPP (820 gC m⁻² yr⁻¹). The paper discusses the utility of the flux data and the synergies between flux, remote sensing, and modelling. Lastly, the paper looks ahead at the future direction of the network and concludes that there has been a substantial contribution by OzFlux, and considerable opportunities remain to further advance our understanding of ecosystem response to disturbances, including drought, fire, land-use and land-cover change, land management, and climate change, which are relevant both nationally and internationally. It is suggested that a synergistic approach is required to address all of the spatial, ecological, human, and cultural challenges of managing the delicately balanced ecosystems in Australasia.Jason Beringer ... Wayne Meyer ... et al

Tips for implementing multigrid methods on domains containing holes

As part of our development of a computer code to perform 3D `constrained evolution' of Einstein's equations in 3+1 form, we discuss issues regarding the efficient solution of elliptic equations on domains containing holes (i.e., excised regions), via the multigrid method. We consider as a test case the Poisson equation with a nonlinear term added, as a means of illustrating the principles involved, and move to a "real world" 3-dimensional problem which is the solution of the conformally flat Hamiltonian constraint with Dirichlet and Robin boundary conditions. Using our vertex-centered multigrid code, we demonstrate globally second-order-accurate solutions of elliptic equations over domains containing holes, in two and three spatial dimensions. Keys to the success of this method are the choice of the restriction operator near the holes and definition of the location of the inner boundary. In some cases (e.g. two holes in two dimensions), more and more smoothing may be required as the mesh spacing decreases to zero; however for the resolutions currently of interest to many numerical relativists, it is feasible to maintain second order convergence by concentrating smoothing (spatially) where it is needed most. This paper, and our publicly available source code, are intended to serve as semi-pedagogical guides for those who may wish to implement similar schemes.Comment: 18 pages, 11 figures, LaTeX. Added clarifications and references re. scope of paper, mathematical foundations, relevance of work. Accepted for publication in Classical & Quantum Gravit