Manipulation of the myeloid immune compartment during respiratory infection

Imperial Users onl

MMP-9 cleaves SP-D and abrogates its innate immune functions in vitro

Possession of a properly functioning innate immune system in the lung is vital to prevent infections due to the ongoing exposure of the lung to pathogens. While mechanisms of pulmonary innate immunity have been well studied, our knowledge of how these systems are altered in disease states, leading to increased susceptibility to infections, is limited. One innate immune protein in the lung, the pulmonary collectin SP-D, has been shown to be important in innate immune defense, as well as clearance of allergens and apoptotic cells. MMP-9 is a protease with a wide variety of substrates, and has been found to be dysregulated in a myriad of lung diseases ranging from asthma to cystic fibrosis; in many of these conditions, there are decreased levels of SP-D. Our results indicate that MMP-9 is able to cleave SP-D in vitro and this cleavage leads to loss of its innate immune functions, including its abilities to aggregate bacteria and increase phagocytosis by mouse alveolar macrophages. However, MMP-9-cleaved SP-D was still detected in a solid-phase E. coli LPS-binding assay, while NE-cleaved SP-D was not. In addition, MMP-9 seems to cleave SP-D much more efficiently than NE at physiological levels of calcium. Previous studies have shown that in several diseases, including cystic fibrosis and asthma, patients have increased expression of MMP-9 in the lungs as well as decreased levels of intact SP-D. As patients suffering from many of the diseases in which MMP-9 is over-expressed can be more susceptible to pulmonary infections, it is possible that MMP-9 cleavage of SP-D may contribute to this phenotype

Recyclability of stainless steel (316L) powder within the additive manufacturing process

Using recycled powder during the additive manufacturing processes has been a matter of debate by several research groups and industry worldwide. If not significantly different from the feedstock, the recycled powder can be reused many times without a detrimental impact on the mechanical properties of the final printed parts, which reduces the metallic powder waste and printing time. A detailed characterization and comparison of the feedstock and recycled powders is essential in order to understand the number of times a powder can be recycled. The recycled powders were sampled after 10 times reuse in the Powder Bed Fusion (PBF) process in the 3D printer. In this paper, we have performed a detailed characterization on morphology, microstructure, and the surface and bulk composition of virgin feedstock and recycled stainless steel 316 L powders (over 10 times reused), and correlated these measurements to topography, nanoindentation and hardness tests. We have also performed rarely reported synchrotron surface characterization of both powder sets in order to measure the level of oxidation of the individual metallic elements present in the virgin and recycled steel powder and the way such chemical composition changes following use in the manufacturing process. The results show more satellite and bonded particles in the recycled powder although the particle size is not broadly impacted. The atomic force microscopy results showed a smaller roughness on recycled powders measured on surfaces without satellites which might be due to less surface dendrites on recycled powder surface. Finally, a higher hardness was measured for the recycled powder resulted from the manufacturing process on grains and chemical composition. The results suggest no significant changes on the mechanical properties of the printed parts depending for a certain number of reusing cycles

Sustained desensitization to bacterial Toll-like receptor ligands after resolutionof respiratory influenza infection

The World Health Organization estimates that lower respiratory tract infections (excluding tuberculosis) account for ∼35% of all deaths caused by infectious diseases. In many cases, the cause of death may be caused by multiple pathogens, e.g., the life-threatening bacterial pneumonia observed in patients infected with influenza virus. The ability to evolve more efficient immunity on each successive encounter with antigen is the hallmark of the adaptive immune response. However, in the absence of cross-reactive T and B cell epitopes, one lung infection can modify immunity and pathology to the next for extended periods of time. We now report for the first time that this phenomenon is mediated by a sustained desensitization of lung sentinel cells to Toll-like receptor (TLR) ligands; this is an effect that lasts for several months after resolution of influenza or respiratory syncytial virus infection and is associated with reduced chemokine production and NF-κB activation in alveolar macrophages. Although such desensitization may be beneficial in alleviating overall immunopathology, the reduced neutrophil recruitment correlates with heightened bacterial load during secondary respiratory infection. Our data therefore suggests that post-viral desensitization to TLR signals may be one possible contributor to the common secondary bacterial pneumonia associated with pandemic and seasonal influenza infection

Thermal and plasma enhanced atomic layer deposition of ultrathin TiO2 on silicon from amide and alkoxide precursors: growth chemistry and photoelectrochemical performance

Due to its low cost and suitable band gap, silicon has been studied as a photoanode material for some time. However, as a result of poor stability during the oxygen evolution reaction (OER), Si still remains unsuitable for any extended use. Ultra-thin titanium dioxide (TiO2) films have been used as protective coatings and are shown to enhance Si photoanode lifetime with added solar to hydrogen performance improvements through distancing the oxidation reaction away from the Si photoanode surface and improved charge transport through the anode. This study details the nucleation, growth chemistry, and performance of TiO2 thin films prepared via thermal and plasma enhanced atomic layer deposition (ALD) using both titanium isopropoxide and tetrakis(dimethylamido)titanium as the precursor material. The effect of post ALD treatments of plasma and air annealing was also studied. Films were investigated using photoelectrochemical cell testing to evaluate photoelectrochemical performance, and in-vacuum cycle-by-cycle x-ray photoelectron spectroscopy was used as the primary characterisation technique to study nucleation mechanisms and film properties contributing to improvements in cell performance. TiO2 grown by plasma enhanced ALD results in cleaner films with reduced carbon incorporation. However, despite increased carbon incorporation, thermally grown films showed improved photocurrent as a result of oxygen vacancies in these films. Post deposition annealing in a H2 ambient is shown to further improve photocurrent in all cases, while annealing in atmosphere leads to uniform film chemistry and enhanced photocurrent stability in all cases

A new method for assessing the recyclability of powders within Powder Bed Fusion process

Recycling metallic powders used in the additive manufacturing (AM) process is essential for reducing the process cost, manufacturing time, energy consumption, and metallic waste. In this paper, the focus is on pore formation in recycled powder particles of stainless steel 316L during the selective laser melting process. We have introduced the concept of optimizing the powder bed's printing area in order to see the extent of the affected powders during the 3D-printing process. X-ray Computed Tomography (XCT) is used to characterize the pores inside the particles. The results from image processing of the tomography (rendered in 3D format) indicate a broader pore size distribution and a higher pore density in recycled powders compared to their virgin counterparts. To elucidate on this, the Electron Dispersion spectroscopy (EDX) analysis and Synchrotron-based Hard X-ray Photoelectron Spectroscopy (HAXPES) were performed to reveal the chemical composition distribution across the pore area and bulk of the recycled powder particles. Higher concentrations of Fe, Cr, and Ni were recorded on the interior wall of the pore in recycled particles and higher Mn, S and Si concentrations were recorded in the outer layer around the pore area and on the surface of the recycled particle. The pore formation in recycled powder is attributed to out-diffusion of Mn, S and Si to the outer surface as a result of the incident laser heat during the AM process due to higher electron affinity of such metallic elements to oxygenation. HAXPES analysis shows a higher MnO concentration around the pore area which impedes the in-diffusion of other elements into the bulk and thereby helps to creates a void. The inside wall of the pore area (dendrites), has a higher concentration of Fe and Cr oxide. We believe the higher pore density in recycled powders is due, at least in part to composition redistribution, promoted by laser heat during the AM process. Nanoindentation analyses on both virgin and recycled powder particles shows a lower hardness and higher effective modulus in the recycled powder particles attributed to the higher porosity in recycled powders

Hard X-ray photoelectron spectroscopy study of copper formation by metal salt inclusion in a polymer film

In this work we present the results of a Hard X-ray Photoelectron Spectroscopy (HAXPES) study on the creation of metallic copper layers via metal-salt infiltration into a poly-2-vinylpyridine (P2VP) film. Metal salt inclusion is a wet chemistry process which allows for the fabrication of both metal and metal oxide films by means of infiltrating a receptive polymer thin film with metal salt precursors. A copper infiltrated P2VP film was subject to UV/Ozone treatment to form copper oxide and annealed in-vacuo to reduce the film to metallic copper. HAXPES and transmission electron microscope (TEM) measurements were used to study the polymer film before and after metal salt infiltration, along with analysis of the copper oxide created after UV/Ozone treatment. The results show successful infiltration of the metal salt into the polymer film, as well as complete conversion to copper oxide following UV/Ozone treatment and reduction to metallic copper with a subsequent in-situ anneal, which demonstrates the ability of the technique for the creation of several key integrated circuit features

Analysing trimethylaluminum infiltration intopolymer brushes using a scalable area selectivevapor phase process

Developing vapor phase infiltration (VPI) processes for area selective polymer nanopatterning requires substantial advancement in understanding precursor infiltration, precursor–polymer interaction and process parameters. In this work, infiltration receptive poly(2-vinylpyridine) (P2VP) and poly(4-vinylpyridine) (P4VP) brushes were exposed to a trimethylaluminum (TMA) VPI process and compared toa non-receptive polystyrene (PS) system. The interaction that takes place between TMA and P2VP/P4VPwas analysed in detail and we report on notable advantages in the use of P4VP, arising from the difference in position of the pyridinic nitrogen. The VPI process was performed in a commercial atomic layer deposition reactor and the effects of the fundamental process parameters on the three polymer brushes were investigated to ensure optimal area selectivity. In situX-ray photoelectron spectroscopy (XPS) measurements were supported by grazing angle Fourier transform infrared spectroscopy (GA-FTIR)and hard X-ray photoelectron spectroscopy (HAXPES). The report identifies several important factors when developing a VPI process to ensure area selectivity, while also demonstrating the use of novel pyridine containing polymers for VPI area selective purposes

A systematic review and meta-synthesis of the impact of low back pain on people's lives

Copyright @ 2014 Froud et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.Background - Low back pain (LBP) is a common and costly problem that many interpret within a biopsychosocial model. There is renewed concern that core-sets of outcome measures do not capture what is important. To inform debate about the coverage of back pain outcome measure core-sets, and to suggest areas worthy of exploration within healthcare consultations, we have synthesised the qualitative literature on the impact of low back pain on people’s lives. Methods - Two reviewers searched CINAHL, Embase, PsycINFO, PEDro, and Medline, identifying qualitative studies of people’s experiences of non-specific LBP. Abstracted data were thematic coded and synthesised using a meta-ethnographic, and a meta-narrative approach. Results - We included 49 papers describing 42 studies. Patients are concerned with engagement in meaningful activities; but they also want to be believed and have their experiences and identity, as someone ‘doing battle’ with pain, validated. Patients seek diagnosis, treatment, and cure, but also reassurance of the absence of pathology. Some struggle to meet social expectations and obligations. When these are achieved, the credibility of their pain/disability claims can be jeopardised. Others withdraw, fearful of disapproval, or unable or unwilling to accommodate social demands. Patients generally seek to regain their pre-pain levels of health, and physical and emotional stability. After time, this can be perceived to become unrealistic and some adjust their expectations accordingly. Conclusions - The social component of the biopsychosocial model is not well represented in current core-sets of outcome measures. Clinicians should appreciate that the broader impact of low back pain includes social factors; this may be crucial to improving patients’ experiences of health care. Researchers should consider social factors to help develop a portfolio of more relevant outcome measures.Arthritis Research U

Themis2/ICB1 Is a Signaling Scaffold That Selectively Regulates Macrophage Toll-Like Receptor Signaling and Cytokine Production

BACKGROUND: Thymocyte expressed molecule involved in selection 1 (Themis1, SwissProt accession number Q8BGW0) is the recently characterised founder member of a novel family of proteins. A second member of this family, Themis2 (Q91YX0), also known as ICB1 (Induced on contact with basement membrane 1), remains unreported at the protein level despite microarray and EST databases reporting Themis2 mRNA expression in B cells and macrophages. METHODOLOGY/PRINCIPAL FINDINGS: Here we characterise Themis2 protein for the first time and show that it acts as a macrophage signalling scaffold, exerting a receptor-, mediator- and signalling pathway-specific effect on TLR responses in RAW 264.7 macrophages. Themis2 over-expression enhanced the LPS-induced production of TNF but not IL-6 or Cox-2, nor TNF production induced by ligands for TLR2 (PAM3) or TLR3 (poly IratioC). Moreover, LPS-induced activation of the MAP kinases ERK and p38 was enhanced in cells over-expressing Themis2 whereas the activation of JNK, IRF3 or NF-kappaB p65, was unaffected. Depletion of Themis2 protein by RNA inteference inhibited LPS-induced TNF production in primary human macrophages demonstrating a requirement for Themis2 in this event. Themis2 was inducibly tyrosine phosphorylated upon LPS challenge and interacted with Lyn kinase (P25911), the Rho guanine nucleotide exchange factor, Vav (P27870), and the adaptor protein Grb2 (Q60631). Mutation of either tyrosine 660 or a proline-rich sequence (PPPRPPK) simultaneously interrupted this complex and reduced by approximately 50% the capacity of Themis2 to promote LPS-induced TNF production. Finally, Themis2 protein expression was induced during macrophage development from murine bone marrow precursors and was regulated by inflammatory stimuli both in vitro and in vivo. CONCLUSIONS/SIGNIFICANCE: We hypothesise that Themis2 may constitute a novel, physiological control point in macrophage inflammatory responses