Surfactant protein genetics in community-acquired pneumonia: balancing the host inflammatory state

Community-acquired pneumonia is a common disease. Abnormalities in the first step of host defense may severely compromise subsequent steps of successfully combating infections. In the previous issue of Critical Care, García-Laorden and colleagues reported genetic associations between single-nucleotide polymorphisms and haplotypes of the surfactant proteins with susceptibility, severity, and outcome of community-acquired pneumonia. Although the limited information shows regulatory differences among variants, it is currently unknown how the difference in surfactant protein A genotypes in this and other studies affects the individual's phenotype. The lung is continually exposed to a host of irritants yet maintains health. It is plausible that, under physiologic conditions, surfactant protein A, in addition to having a dominant effect on anti-inflammatory processes, mediates a low level of proinflammatory processes that are essential for the health of the lung. Understanding the maintenance of the balance of the inflammatory state may be one of the keys to understanding pulmonary disease progression

Dual barrier InAlN/AlGaN/GaN-on-silicon high-electron-mobility transistors with Pt and Ni based gate stacks

In this work, we report the performance of 3 μm gate length "dual barrier„ InAlN/AlGaN/GaN HEMTs on Si substrates with gate-drain contact separations in the range 4-26 μm. Devices with Pt and Ni based gates were studied and their leakage characteristics are compared. Maximum drain current IDS of 1 A/mm, maximum extrinsic transconductance gm ~203 mS/mm and on-resistance Ron 4.07 Ω mm for gate to drain distance LGD = 4 μm were achieved. Nearly ideal sub-threshold swing of 65.6 mV/dec was obtained for LGD = 14 μm. The use of Pt based gate metal stacks led to a two to three orders of magnitude gate leakage current decrease compared to Ni based gates. The influence of InAlN layer thickness on the transistor transfer characteristics is also discussed

Surfactant protein A and D polymorphisms and methylprednisolone pharmacogenetics in donor lungs

Objective: Surfactant proteins A and D are important molecules involved in lung allograft innate immunity. Genetic polymorphisms of surfactant proteins A and D are associated with various lung diseases. In this study, surfactant protein A and D expression responses were investigated during pharmacogenetics upon methylprednisolone treatment as observed during lung transplantation. Methods: A human cell line (NCI-H441) and precision-cut lung slices from 16 human donors were incubated with methylprednisolone, and surfactant protein A1, surfactant protein A2, and surfactant protein D messenger RNA and surfactant protein A protein expression were assayed. Surfactant protein A1, A2, and D polymorphisms and surfactant protein A gene and protein expressions were determined. Results: In NCI-H441 cells, methylprednisolone treatment at 10−5 M and 10−6 M reduced surfactant protein A1 and surfactant protein A2 messenger RNA and surfactant protein A protein expression (P <.05). A pharmacogenetic relationship was observed in human donor precision-cut lung slices between the surfactant protein A2 (1Ax) variants: Surfactant protein A1, A2, and D messenger RNA expression were greater for 1A0 versus 1A1 (P <.05); surfactant protein A1/surfactant protein A2 genotype 6A26A2/1A01A0 (n = 5) showed greater surfactant protein A1, A2, and D messenger RNA expression and surfactant protein A protein expression compared with the other surfactant protein A1/surfactant protein A2 genotypes (n = 11) (P <.05). Conclusions: The surfactant protein A genotype and methylprednisolone stimuli influence donor lung surfactant protein A and D expression. Lungs carrying the surfactant protein A2 variant 1A0 have a greater expression of surfactant protein A when treated with methylprednisolone. Surfactant protein A polymorphisms could be used to personalize immunosuppressive regimens

Impact of stress in ICP-CVD SiN x passivation films on the leakage current in AlGaN/GaN HEMTs

The impact of the stress in room temperature inductively coupled plasma chemical vapour deposited (ICP-CVD) SiN x surface passivation layers on off-state drain ( I DS-off) and gate leakage currents ( I GS) in AlGaN/GaN high electron mobility transistors (HEMTs) is reported. I DS-off and I GS in 2 μm gate length devices were reduced by up to four orders of magnitude to ∼10 pA/mm using a compressively stressed bilayer SiN x passivation scheme. In addition, I on/ I off of ∼10 11 and subthreshold slope of 68 mV/dec were obtained using this strain engineered surface passivation approach

Donor Surfactant Protein A2 Polymorphism and Lung Transplant Survival.

Purpose Gene polymorphisms of surfactant proteins, key players in lung innate immunity, have been associated with various lung diseases. The aim of this study was to investigate the potential association between variations within the SP-A gene of the donor lung allograft and recipient post-transplant outcome. Methods Lung-Tx pts (n=192) were prospectively followed by PFTs, bronchoscopies with BAL and biopsies. Donor lungs were assayed for SP-A1 (6An) and SP-A2 (1An) gene polymorphism by using the pyrosequencing method. Unadjusted and adjusted stratified Cox survival models are reported. Results SP-A1 and SP-A2 genotype frequency and lung transplant recipient and donor characteristics as well as the cause of death are noted. Recipients were grouped per donor SP-A2 variants. Individuals that received lungs from donors with the SP-A2 1A0 (n=102) versus 1A1 variant (n=68) or SPA2 genotype 1A01A0 (n=54) versus 1A0A1 (n=38) had greater survival at one year (logrank p<0.025). No significant association was noted for SP-A1 variants. Stratified adjusted survival models for one year survival and diagnosis showed a reduced survival for 1A1 variant and the 1A01A1 genotype. Furthermore, when survival was conditional on one year survival no significance was observed, indicating that the survival difference were due to the first year's outcome associated with the 1A1 variant. Conclusion Donor lung SP-A gene polymorphisms are associated with post-transplant clinical outcome. Lungs from donors with the SP-A2 variant 1A1 had a reduced survival at one year. The observed donor genetic differences, via innate immunity relate to the post-transplant clinical outcome.PURPOSE: Gene polymorphisms of surfactant proteins, key players in lung innate immunity, have been associated with various lung diseases. The aim of this study was to investigate the potential association between variations within the SP-A gene of the donor lung allograft and recipient post-transplant outcome. METHODS: Lung-Tx pts (n=192) were prospectively followed by PFTs, bronchoscopies with BAL and biopsies. Donor lungs were assayed for SP-A1 (6An) and SP-A2 (1An) gene polymorphism by using the pyrosequencing method. Unadjusted and adjusted stratified Cox survival models are reported. RESULTS: SP-A1 and SP-A2 genotype frequency and lung transplant recipient and donor characteristics as well as the cause of death are noted. Recipients were grouped per donor SP-A2 variants. Individuals that received lungs from donors with the SP-A2 1A0 (n=102) versus 1A1 variant (n=68) or SPA2 genotype 1A01A0 (n=54) versus 1A0A1 (n=38) had greater survival at one year (logrank p<0.025). No significant association was noted for SP-A1 variants. Stratified adjusted survival models for one year survival and diagnosis showed a reduced survival for 1A1 variant and the 1A01A1 genotype. Furthermore, when survival was conditional on one year survival no significance was observed, indicating that the survival difference were due to the first year's outcome associated with the 1A1 variant. CONCLUSION: Donor lung SP-A gene polymorphisms are associated with post-transplant clinical outcome. Lungs from donors with the SP-A2 variant 1A1 had a reduced survival at one year. The observed donor genetic differences, via innate immunity relate to the post-transplant clinical outcome

Mass Spectrometry Based Molecular 3D-Cartography of Plant Metabolites

Plants play an essential part in global carbon fixing through photosynthesis and are the primary food and energy source for humans. Understanding them thoroughly is therefore of highest interest for humanity. Advances in DNA and RNA sequencing and in protein and metabolite analysis allow the systematic description of plant composition at the molecular level. With imaging mass spectrometry, we can now add a spatial level, typically in the micrometer-to-centimeter range, to their compositions, essential for a detailed molecular understanding. Here we present an LC-MS based approach for 3D plant imaging, which is scalable and allows the analysis of entire plants. We applied this approach in a case study to pepper and tomato plants. Together with MS/MS spectra library matching and spectral networking, this non-targeted workflow provides the highest sensitivity and selectivity for the molecular annotations and imaging of plants, laying the foundation for studies of plant metabolism and plant-environment interactions