Identification of the Flagellin Glycosylation System in Burkholderia cenocepacia and the Contribution of Glycosylated Flagellin to Evasion of Human Innate Immune Responses

Burkholderia cenocepacia is an opportunistic pathogen threatening patients with cystic fibrosis. Flagella are required for biofilm formation, as well as adhesion to and invasion of epithelial cells. Recognition of flagellin via the Toll-like receptor 5 (TLR5) contributes to exacerbate B. cenocepacia-induced lung epithelial inflammatory responses. In this study, we report that B. cenocepacia flagellin is glycosylated on at least 10 different sites with a single sugar, 4,6-dideoxy-4-(3-hydroxybutanoylamino)-d-glucose. We have identified key genes that are required for flagellin glycosylation, including a predicted glycosyltransferase gene that is linked to the flagellin biosynthesis cluster and a putative acetyltransferase gene located within the O-antigen lipopolysaccharide cluster. Another O-antigen cluster gene, rmlB, which is required for flagellin glycan and O-antigen biosynthesis, was essential for bacterial viability, uncovering a novel target against Burkholderia infections. Using glycosylated and nonglycosylated purified flagellin and a cell reporter system to assess TLR5-mediated responses, we also show that the presence of glycan in flagellin significantly impairs the inflammatory response of epithelial cells. We therefore suggest that flagellin glycosylation reduces recognition of flagellin by host TLR5, providing an evasive strategy to infecting bacteria.

A Spherical Array Approach for Simulation of Binaural Impulse Responses using the Finite Difference Time Domain Method

The finite difference time domain (FDTD) method has direct applications in musical instrument modeling, simulation of environmental acoustics, room acoustics and sound reproduction paradigms, all of which benefit from auralization. However, rendering binaural impulse responses from simulated
data is not straightforward to accomplish as the calculated pressure at FDTD grid nodes does not contain any directional information. This paper addresses this issue by introducing a spherical array to capture sound pressure on a finite difference grid, and decomposing it into a plane-wave density
function. Binaural impulse responses are then constructed in the spherical harmonics domain by combining the decomposed grid data with free field head-related transfer functions. The effects of designing a spherical array in a Cartesian grid are studied, and emphasis is given to the relationships
between array sampling and the spatial and spectral design parameters of several finite-difference
schemes.

Expansion of pulse responses from temporal analysis of products (TAP) pulse responses for more accurate data analysis

TAP pulse responses are normally analysed using moments, which are integrals of the full TAP pulse response. However, in some cases the entire pulse response may not be recorded due to technical reasons, thereby compromising any data analysis due to moments generated from incomplete pulse responses. The current work discloses the development of a function which mathematically expands the tail of a TAP pulse response, so that the TAP data analysis can be accurately conducted. This newly developed analysis method has been applied to the oxidative dehydrogenation of ethane over Co–Cr–Sn–WOx/α-Al2O3 and Co–Cr–Sn–WOx/α-Al2O3 catalysts as a case study.

Dissolving Microneedle Delivery of Nanoparticle Encapsulated Antigen Elicits Efficient Cross-Priming and Th1 Immune Responses by Murine Langerhans Cells

Dendritic cells (DCs) of the skin play an important role in skin-mediated immunity capable of promoting potent immune responses. We availed of polymeric dissolving microneedle (MN) arrays laden with nano-encapsulated antigen to specifically target skin DC networks. This modality of immunization represents an economic, efficient and potent means of antigen delivery directly to skin DCs, which are inefficiently targeted by more conventional immunization routes. Following MN immunization, Langerhans cells (LCs) constituted the major skin DC subset capable of cross-priming antigen-specific CD8(+) T cells ex-vivo. While all DC subsets were equally efficient in priming CD4(+) T cells, LCs were largely responsible for orchestrating the differentiation of CD4(+) IFN-γ and IL-17 producing effectors. Importantly, depletion of LCs prior to immunization had a profound effect on CD8(+) CTL responses in vivo, and vaccinated animals displayed reduced protective anti-tumour and viral immunity. Interestingly, this cross-priming bias was lost following MN immunization with soluble antigen, suggesting that processing and cross-presentation of nano-particulate antigen is favoured by LCs. Therefore, these studies highlight the importance of LCs in skin immunization strategies and that targeting of nano-particulate immunogens through dissolvable polymeric MNs potentially provides a promising technological platform for improved vaccination strategies.Journal of Investigative Dermatology accepted article preview online, 22 September 2014. doi:10.1038/jid.2014.415.

Efficient Network in Player and Partner Heterogeneity Models

This paper characterizes efficient networks in player and partner heterogeneity models for both the one-way flow and the two-way flow models. Player (partner) dependent network formation allows benefits and costs to be player (partner) heterogeneous which is an important extension for modeling social networks in the real world. Employing widely used assumptions, I show that efficient networks in the two way flow model are minimally connected and have star or derivative of star type architectures, whereas efficient networks in the one way flow model have wheel architectures.

Type-I interferons induce lung protease responses following respiratory syncytial virus infection via RIG-I-like receptors

The role of proteases in viral infection of the lung is poorly understood. Thus, we examined matrix metalloproteinases (MMPs) and cathepsin proteases in respiratory syncytial virus (RSV)-infected mouse lungs. RSV-induced gene expression for MMPs -2, -3, -7, -8, -9, -10, -12, -13, -14, -16, -17, -19, -20, -25, -27, and -28 and cathepsins B, C, E, G, H, K, L1, S, W, and Z in the airways of Friend leukemia virus B sensitive strain mice. Increased proteases were present in the bronchoalveolar lavage fluid (BALF) and lung tissue during infection. Mitochondrial antiviral-signaling protein (MAVS) and TIR-domain-containing adapter-inducing interferon-β-deficient mice were exposed to RSV. Mavs-deficient mice had significantly lower expression of airway MMP-2, -3, -7, -8, -9, -10, -12, -13, and -28 and cathepsins C, G, K, S, W, and Z. In lung epithelial cells, retinoic acid-inducible gene-1 (RIG-I) was identified as the major RIG-I-like receptor required for RSV-induced protease expression via MAVS. Overexpression of RIG-I or treatment with interferon-β in these cells induced MMP and cathepsin gene and protein expression. The significance of RIG-1 protease induction was demonstrated by the fact that inhibiting proteases with batimastat, E64 or ribavirin prevented airway hyperresponsiveness and enhanced viral clearance in RSV-infected mice.

Applying imagined contact to improve physiological responses in anticipation of intergroup interactions and the perceived quality of these interactions

This experiment (N 5 49) is the first to show that imagined contact can bufferanticipatory physiological responses to future interactions, and improve the qualityof these interactions. Participants imagined a positive interaction with a person withschizophrenia, or in a control condition, a person who did not have schizophrenia. They then interacted with a confederate whom they believed had schizophrenia. Participants in the imagined contact condition reported more positive attitudes andless avoidance of people with schizophrenia, displayed smaller anticipatory physio-logical responses, specifically smaller changes in interbeat interval and skin conduct-ance responses, and had a more positive interaction according to the confederate.These findings support applying imagined contact to improve interactions with people with severe mental illnesses.