IL-17 can be protective or deleterious in murine pneumococcal pneumonia

Streptococcus pneumoniae is the major bacterial cause of community-acquired pneumonia, and the leading agent of childhood pneumonia deaths worldwide. Nasal colonization is an essential step prior to infection. The cytokine IL-17 protects against such colonization and vaccines that enhance IL-17 responses to pneumococcal colonization are being developed. The role of IL-17 in host defence against pneumonia is not known. To address this issue, we have utilized a murine model of pneumococcal pneumonia in which the gene for the IL-17 cytokine family receptor, Il17ra, has been inactivated. Using this model, we show that IL-17 produced predominantly from γδ T cells protects mice against death from the invasive TIGR4 strain (serotype 4) which expresses a relatively thin capsule. However, in pneumonia produced by two heavily encapsulated strains with low invasive potential (serotypes 3 and 6B), IL-17 significantly enhanced mortality. Neutrophil uptake and killing of the serotype 3 strain was significantly impaired compared to the serotype 4 strain and depletion of neutrophils with antibody enhanced survival of mice infected with the highly encapsulated SRL1 strain. These data strongly suggest that IL-17 mediated neutrophil recruitment to the lungs clears infection from the invasive TIGR4 strain but that lung neutrophils exacerbate disease caused by the highly encapsulated pneumococcal strains. Thus, whilst augmenting IL-17 immune responses against pneumococci may decrease nasal colonization, this may worsen outcome during pneumonia caused by some strains

Overexpression, purification and crystallization of a choline-binding protein CbpI from Streptococcus pneumoniae

The choline-binding protein CbpI from S. pneumoniae has been purified and crystallized and diffraction data have been collected to 3.5 Å resolution

Combining AIRS and MLS observations for three-dimensional gravity wave measurement

Gravity waves play a critical role in transporting energy and momentum between the troposphere, stratosphere, and mesosphere. Satellite measurements provide a powerful tool to investigate these waves across the globe. However, many present methods cannot yield reliable estimates of wave momentum fluxes or the directions of these fluxes. Here we present a new method which addresses this problem by combining observations from Atmospheric Infrared Sounder (AIRS) and Microwave Limb Sounder (MLS) in three dimensions. The method allows direct estimation of horizontal and vertical wavelengths as well as wave amplitude. This in turn allows estimation of both wave momentum flux and the full 3-D direction of propagation, crucially including the horizontal direction. The method thus allows separation of the data into, for example, eastward and westward momentum fluxes, allowing estimation of the net atmospheric forcing due to these waves. We illustrate this method with a proof-of-concept study over the Andes, arguably the largest source of gravity waves in the world. We further critically assess the advantages and disadvantages of our method. Our study highlights the importance of the difference between net and absolute measures of momentum flux

Application of Structured Decision Making to Wildlife Management in Montana

Good decision-making is essential to conserving wildlife populations. Whereas there may be multiple ways to address a problem, perfect solutions rarely exist. Managers are therefore tasked with identifying optimal decisions that will best achieve desired outcomes. Structured decision making (SDM) is a method of decision analysis used to identify the most effective, efficient, and realistic optimal decisions while accounting for values and priorities of the decision maker. The stepwise process includes identifying the management problem, defining objectives for solving the problem, developing alternative approaches to achieve the objectives, and formally evaluating which alternative is most likely to accomplish the objectives. The SDM process can be more effective than informal decision-making because it provides a transparent way to quantitatively evaluate decisions for addressing multiple management objectives while incorporating science, uncertainty, and risk tolerance. We illustrate the application of this process to management needs, including an SDM-based decision tool developed to identify optimal decisions for proactively managing risk of pneumonia epizootics in bighorn sheep (Ovis canadensis). Pneumonia epizootics are a major challenge for managers, including in terms of knowing how or when to manage risk. The decision tool facilitates analysis of alternative decisions for how to manage herds based on predictions from a risk model, herd-specific objectives, and predicted costs and benefits of each alternative. Managers can be confident resulting decisions are most effective, efficient, and realistic because they explicitly account for important considerations managers implicitly weigh when making decisions, including competing management objectives, uncertainty in potential outcomes and risk tolerance

Application of radio tomographic imaging to HF oblique incidence ray tracing

Radio tomography is a technique for generating images of the spatial structure of ionospheric electron density over a wide area. This paper assesses the potential use of radio tomography in HF oblique propagation and ray tracing applications. Synthetic ionograms produced by ray tracing through tomographic images and ionospheric models have been compared with experimental oblique ionograms from six paths lying close to the image plane in the United Kingdom. In particular, study has been made of the effects of various types of input information used to constrain the vertical electron density structure in the tomographic reconstructions. It was found that use of a fine height resolution (5 km) and incorporation of information from one vertical ionosonde in the reconstruction process makes significant improvements to the overall reliability of the tomographic image. As expected, E layer propagation is better defined using a climatological model than by tomography. However, in comparison with three ionospheric models, use of tomographic images can significantly reduce the RMS error in the determination of the F2 layer maximum usable frequency

Dissociable Neural Substrates for Agentic versus Conceptual Representations of Self

Although humans generally experience a coherent sense of selfhood, we can nevertheless articulate different aspects of self. Recent research has demonstrated that one such aspect of self—conceptual knowledge of one's own personality traits—is subserved by ventromedial prefrontal cortex (vMPFC). Here, we examined whether an alternative aspect of “self”—being an agent who acts to achieve one's own goals—relies on cognitive processes that overlap with or diverge from conceptual operationalizations of selfhood. While undergoing fMRI, participants completed tasks of both conceptual self-reference, in which they judged their own or another person's personality traits, and agentic self-reference, in which they freely chose an object or watched passively as one was chosen. The agentic task failed to modulate vMPFC, despite producing the same memory enhancement frequently observed during conceptual self-referential processing (the “self-reference” effect). Instead, agentic self-reference was associated with activation of the intraparietal sulcus (IPS), a region previously implicated in planning and executing actions. Experiment 2 further demonstrated that IPS activity correlated with later memory performance for the agentic, but not conceptual, task. These results support views of the “self” as a collection of distinct mental operations distributed throughout the brain, rather than a unitary cognitive system

Proactive Management of Pneumonia Epizootics in Bighorn Sheep in Montana—Project Update

Pneumonia epizootics are a major challenge for effective management of bighorn sheep (Ovis canadensis). Approximately half of the herds in Montana have suffered die-offs since the 1980s, many of which were pneumonia events. A set of models that identify risk of pneumonia and the best management decisions given that risk would be of great value for proactive management of pneumonia epizootics. Our first objective is to design and test a risk model that will help predict a herd’s risk of pneumonia. We hypothesize that various factors increase risk through pathogen exposure, pathogen spread, and disease susceptibility. Analysis of these factors comparing herds with and without recent pneumonia histories using Bayesian logistic regression will allow us to design a risk model. Our second objective is to develop a proactive decision model that incorporates estimates of pneumonia risk to help evaluate costs and benefits of alternative proactive actions appropriate to those estimates. We will use a Structured Decision Making framework, which provides a deliberative, transparent, and defensible decision-making process that is particularly valuable in complex decision-making environments such as wildlife disease management. Together the resulting risk and decision models, to be completed this year, will help managers estimate pneumonia risk and identify the best management action based on both the severity of each herd’s predicted risk and costs and benefits of competing management alternatives. Ultimately, this project will demonstrate the development and application of risk and decision models for proactive wildlife health programs in Montana Fish, Wildlife and Parks