A paucigranulocytic asthma host environment promotes the emergence of virulent influenza viral variants

Influenza virus has a high mutation rate, such that within one host different viral variants can emerge. Evidence suggests that influenza virus variants are more prevalent in pregnant and/or obese individuals due to their impaired interferon response. We have recently shown that the non-allergic, paucigranulocytic subtype of asthma is associated with impaired type I interferon production. Here, we seek to address if this is associated with an increased emergence of influenza virus variants. Compared to controls, mice with paucigranulocytic asthma had increased disease severity and an increased emergence of influenza virus variants. Specifically, PB1 mutations exclusively detected in asthmatic mice were associated with increased polymerase activity. Furthermore, asthmatic host-derived virus led to increased disease severity in wild-type mice. Taken together, these data suggest that at least a subset of patients with asthma may be more susceptible to severe influenza and may be a possible source of new influenza virus variants

Effect of width, amplitude, and position of a core mantle boundary hot spot on core convection and dynamo action

Within the fluid iron cores of terrestrial planets, convection and the resulting generation of global magnetic fields are controlled by the overlying rocky mantle. The thermal structure of the lower mantle determines how much heat is allowed to escape the core. Hot lower mantle features, such as the thermal footprint of a giant impact or hot mantle plumes, will locally reduce the heat flux through the core mantle boundary (CMB), thereby weakening core convection and affecting the magnetic field generation process. In this study, we numerically investigate how parametrised hot spots at the CMB with arbitrary sizes, amplitudes, and positions affect core convection and hence the dynamo. The effect of the heat flux anomaly is quantified by changes in global flow symmetry properties, such as the emergence of equatorial antisymmetric, axisymmetric (EAA) zonal flows. For purely hydrodynamic models, the EAA symmetry scales almost linearly with the CMB amplitude and size, whereas self-consistent dynamo simulations typically reveal either suppressed or drastically enhanced EAA symmetry depending mainly on the horizontal extent of the heat flux anomaly. Our results suggest that the length scale of the anomaly should be on the same order as the outer core radius to significantly affect flow and field symmetries. As an implication to Mars and in the range of our model, the study concludes that an ancient core field modified by a CMB heat flux anomaly is not able to heterogeneously magnetise the crust to the present-day level of north–south asymmetry on Mars. The resulting magnetic fields obtained using our model either are not asymmetric enough or, when they are asymmetric enough, show rapid polarity inversions, which are incompatible with thick unidirectional magnetisation

Synthesis and solid state structures of N,N'-linked carbazoles and indoles

The synthesis and solid state conformations of a number of N,N'-linked carbazoles and indoles has been investigated. Using xylyl-based linkers, the o, m and p-linked carbazoles and indoles 4-6, 8-10 and 12, 13 were prepared, Likewise, unsymmetrical derivatives were also prepared. Investigation using X-ray crystallography showed that the heterocycles adopted either stretched or folded conformations in the solid state. (C) 2002 Elsevier Science Ltd. All rights reserved.</p

Quantitative analysis of adsorbate induced segregation at bimetallic surfaces: improving the accuracy of medium energy ion scattering results

Bimetallic systems respond dynamically to the nature of the gas phase in contact with the surface. The development of a surface analytical tool which probes the layer by layer composition of a bimetallic surface covered by an adsorbate would be of great benefit in understanding complex catalytic and corrosion processes. This paper examines critically the possibility of using medium energy ion scattering to obtain such information. The unique shadowing and blocking capabilities of this technique make it possible, in principle, to selectively illuminate integer numbers of surface layers. As the physics of the incident ion-surface atom collision is well established, it should then be possible to effectively count the number of each atom type present in the first layer, the top two layers, the top three layers, etc., of the bimetallic surface, thereby giving quantitative compositional information. Using a combination of experiment and simulation, we investigate how the number of layers illuminated depends on the extent of the surface layer relaxation, the adsorbate and the surface Debye temperature. We calculate the layer compositions of the top three layers in the Cu50Pd50(110)/C2H4-xClx system. We show that hydrocarbon adsorption produces a measurable Pd enrichment in the surface layer, while Cu enrichment is produced by the presence of Cl(ads) and C(ads)

The dynamic catalytic surface: probing bimetallic active sites with medium energy ion scattering

The shadowing and blocking effects exhibited by medium energy ion scattering (MEIS) make it a uniquely effective technique for the analysis of the layer composition of bimetallic surfaces. We use MEIS to study adsorbate-induced segregation effects at the Cu50Pd50(110) surface. We show that the clean surface composition is strongly dependent on sample preparation. In addition, the adsorption of chlorohydrocarbons causes substantial surface layer Cu enrichment (up to 100% Cu), whereas hydrocarbon adsorption causes Pd enrichment. We propose an explanation for the magnitude of these segregation effects in terms of the surface chemistry of these molecule

Glycemic Variability in Diabetes Increases the Severity of Influenza.

People with diabetes are two times more likely to die from influenza than people with no underlying medical condition. The mechanisms underlying this susceptibility are poorly understood. In healthy individuals, small and short-lived postprandial peaks in blood glucose levels occur. In diabetes mellitus, these fluctuations become greater and more frequent. This glycemic variability is associated with oxidative stress and hyperinflammation. However, the contribution of glycemic variability to the pathogenesis of influenza A virus (IAV) has not been explored. Here, we used an in vitro model of the pulmonary epithelial-endothelial barrier and novel murine models to investigate the role of glycemic variability in influenza severity. In vitro, a history of glycemic variability significantly increased influenza-driven cell death and destruction of the epithelial-endothelial barrier. In vivo, influenza virus-infected mice with a history of glycemic variability lost significantly more body weight than mice with constant blood glucose levels. This increased disease severity was associated with markers of oxidative stress and hyperinflammation both in vitro and in vivo Together, these results provide the first indication that glycemic variability may help drive the increased risk of severe influenza in people with diabetes mellitus.IMPORTANCE Every winter, people with diabetes are at increased risk of severe influenza. At present, the mechanisms that cause this increased susceptibility are unclear. Here, we show that the fluctuations in blood glucose levels common in people with diabetes are associated with severe influenza. These data suggest that glycemic stability could become a greater clinical priority for patients with diabetes during outbreaks of influenza

A high fat diet increases influenza A virus-associated cardiovascular damage

BACKGROUND: Influenza A virus (IAV) causes a wide range of extra-respiratory complications. However, the role of host factors in these complications of influenza virus infection remains to be defined. METHODS: Here, we sought to use transcriptional profiling, virology, histology and echocardiograms to investigate the role of a high fat diet in IAV associated cardiac damage. RESULTS: Transcriptional profiling showed that, compared to their low fat (LF) counterparts, mice fed a high fat (HF) diet had impairments in inflammatory signalling in the lung and heart after IAV infection. This was associated with increased viral titres in the heart, increased left ventricular mass and thickening of the left ventricular wall in IAV-infected HF mice compared to both IAV-infected LF mice and uninfected HF mice. Retrospective analysis of clinical trials revealed that cardiac complications were more common in patients with excess weight, an association which was significant in 2 out of 4 studies. CONCLUSIONS: Together, these data provide the first evidence that a high fat diet may be a risk factor for the development of IAV-associated cardiovascular damageand emphasises the need for further clinical research in this area