Characterisation of Innate Fungal Recognition in the Lung

The innate recognition of fungi by leukocytes is mediated by pattern recognition receptors (PRR), such as Dectin-1, and is thought to occur at the cell surface triggering intracellular signalling cascades which lead to the induction of protective host responses. In the lung, this recognition is aided by surfactant which also serves to maintain the balance between inflammation and pulmonary function, although the underlying mechanisms are unknown. Here we have explored pulmonary innate recognition of a variety of fungal particles, including zymosan, Candida albicans and Aspergillus fumigatus, and demonstrate that opsonisation with surfactant components can limit inflammation by reducing host-cell fungal interactions. However, we found that this opsonisation does not contribute directly to innate fungal recognition and that this process is mediated through non-opsonic PRRs, including Dectin-1. Moreover, we found that pulmonary inflammatory responses to resting Aspergillus conidia were initiated by these PRRs in acidified phagolysosomes, following the uptake of fungal particles by leukocytes. Our data therefore provides crucial new insights into the mechanisms by which surfactant can maintain pulmonary function in the face of microbial challenge, and defines the phagolysosome as a novel intracellular compartment involved in the innate sensing of extracellular pathogens in the lung

British press attitudes towards the EU's global presence:from the Russian-Georgian War to the 2009 Copenhagen Summit

This article surveys the way in which British print media have presented the European Union (EU)'s global presence in the international arena by analysing two case studies which reflect two very distinctive areas of EU foreign policy: global climate change policy and the policy towards Russia. It employs frame analysis, allowing for the identification of the way in which the discourse of the press was categorized around a series of central opinions and ideas. Frames underscore the connections made by journalists between different events, policies or phenomena and their possible interpretations. The analysis highlights that acting through the common framework of the EU rather than unilaterally was a strategy preferred by the British press. These findings are in stark contrast with the deep Euroscepticism which characterizes press attitudes towards most policy areas, and is often considered to be rooted in the British political culture, media system, public opinion or the longstanding tradition of viewing the European continent as the other

An Efficient and Versatile System for Visualization and Genetic Modification of Dopaminergic Neurons in Transgenic Mice.

BACKGROUND & AIMS: The brain dopaminergic (DA) system is involved in fine tuning many behaviors and several human diseases are associated with pathological alterations of the DA system such as Parkinson's disease (PD) and drug addiction. Because of its complex network integration, detailed analyses of physiological and pathophysiological conditions are only possible in a whole organism with a sophisticated tool box for visualization and functional modification. METHODS & RESULTS: Here, we have generated transgenic mice expressing the tetracycline-regulated transactivator (tTA) or the reverse tetracycline-regulated transactivator (rtTA) under control of the tyrosine hydroxylase (TH) promoter, TH-tTA (tet-OFF) and TH-rtTA (tet-ON) mice, to visualize and genetically modify DA neurons. We show their tight regulation and efficient use to overexpress proteins under the control of tet-responsive elements or to delete genes of interest with tet-responsive Cre. In combination with mice encoding tet-responsive luciferase, we visualized the DA system in living mice progressively over time. CONCLUSION: These experiments establish TH-tTA and TH-rtTA mice as a powerful tool to generate and monitor mouse models for DA system diseases

Evaluation design of a reactivation care program to prevent functional loss in hospitalised elderly: A cohort study including a randomised controlled trial

Background: Elderly persons admitted to the hospital are at risk for hospital related functional loss. This evaluation aims to compare the effects of different levels of (integrated) health intervention care programs on preventing hospital related functional loss among elderly patients by comparing a new intervention program to two usual care progra

SEABED INFRASTRUCTURE DEFENSE ANALYSIS

Traditional fleet operations and technologies are not adequately suited to counter the growing threat to undersea infrastructure from autonomous undersea systems. A cost-effective unmanned and manned system of systems is required to provide defense of this seabed infrastructure. This paper proposes possible system architectures to defend against this emerging threat to include passive barriers and active defense systems. The effectiveness of those candidate systems is evaluated through multiple agent-based modeling simulations of UUV versus UUV engagements. Analysis resulted in two major findings. First, point defense of critical assets is more effective than barrier defense. Second, system design must focus on minimizing the time required to effectively engage and neutralize threats, either through improvement to defensive UUV speed or investment in more UUV docking stations and sensor arrays. Cost analysis suggests that acquisition and operations cost of the recommended defensive system is less than the projected financial impact of a successful attack.http://archive.org/details/seabedinfrastruc1094562767Lieutenant, United States NavyLieutenant, United States NavyLieutenant, United States NavyMajor, Israel Defence ForcesMajor, Republic of Singapore Air ForceMajor, Republic of Singapore Air ForceCaptain, Singapore ArmyLieutenant, United States NavyLieutenant, United States NavyLieutenant, United States NavyMajor, Republic of Singapore Air ForceCaptain, Singapore ArmyCivilian, Ministry of Defense, SingaporeLieutenant, United States NavyLieutenant Commander, United States NavyLieutenant Junior Grade, United States NavyCivilian, Ministry of Defense, SingaporeCivilian, Ministry of Defense, SingaporeMajor, Republic of Singapore Air ForceMajor, United States Marine CorpsMajor, Singapore ArmyApproved for public release; distribution is unlimited