Analysis of model Titan atmospheric components using ion mobility spectrometry

The Gas Chromatograph-Ion Mobility Spectrometer (GC-IMS) was proposed as an analytical technique for the analysis of Titan's atmosphere during the Cassini Mission. The IMS is an atmospheric pressure, chemical detector that produces an identifying spectrum of each chemical species measured. When the IMS is combined with a GC as a GC-IMS, the GC is used to separate the sample into its individual components, or perhaps small groups of components. The IMS is then used to detect, quantify, and identify each sample component. Conventional IMS detection and identification of sample components depends upon a source of energetic radiation, such as beta radiation, which ionizes the atmospheric pressure host gas. This primary ionization initiates a sequence of ion-molecule reactions leading to the formation of sufficiently energetic positive or negative ions, which in turn ionize most constituents in the sample. In conventional IMS, this reaction sequence is dominated by the water cluster ion. However, many of the light hydrocarbons expected in Titan's atmosphere cannot be analyzed by IMS using this mechanism at the concentrations expected. Research at NASA Ames and PCP Inc., has demonstrated IMS analysis of expected Titan atmospheric components, including saturated aliphatic hydrocarbons, using two alternate sample ionizations mechanisms. The sensitivity of the IMS to hydrocarbons such as propane and butane was increased by several orders of magnitude. Both ultra dry (waterless) IMS sample ionization and metastable ionization were successfully used to analyze a model Titan atmospheric gas mixture

Interleukin-1α Activity in Necrotic Endothelial Cells Is Controlled by Caspase-1 Cleavage of Interleukin-1 Receptor-2: IMPLICATIONS FOR ALLOGRAFT REJECTION.

Inflammation is a key instigator of the immune responses that drive atherosclerosis and allograft rejection. IL-1α, a powerful cytokine that activates both innate and adaptive immunity, induces vessel inflammation after release from necrotic vascular smooth muscle cells (VSMCs). Similarly, IL-1α released from endothelial cells (ECs) damaged during transplant drives allograft rejection. However, IL-1α requires cleavage for full cytokine activity, and what controls cleavage in necrotic ECs is currently unknown. We find that ECs have very low levels of IL-1α activity upon necrosis. However, TNFα or IL-1 induces significant levels of active IL-1α in EC necrotic lysates without alteration in protein levels. Increased activity requires cleavage of IL-1α by calpain to the more active mature form. Immunofluorescence and proximity ligation assays show that IL-1α associates with interleukin-1 receptor-2, and this association is decreased by TNFα or IL-1 and requires caspase activity. Thus, TNFα or IL-1 treatment of ECs leads to caspase proteolytic activity that cleaves interleukin-1 receptor-2, allowing IL-1α dissociation and subsequent processing by calpain. Importantly, ECs could be primed by IL-1α from adjacent damaged VSMCs, and necrotic ECs could activate neighboring normal ECs and VSMCs, causing them to release inflammatory cytokines and up-regulate adhesion molecules, thus amplifying inflammation. These data unravel the molecular mechanisms and interplay between damaged ECs and VSMCs that lead to activation of IL-1α and, thus, initiation of adaptive responses that cause graft rejection.This study was supported by British Heart Foundation Grants FS/09/005/26845, FS/13/3/30038 and FS/11/77/29327 (MCHC) & RG/13/14/30314 (MRB); the BHF Cambridge CRE; and the NIHR Cambridge BRC.This is the final version of the article. It first appeared from ASBMB via http://dx.doi.org/10.1074/jbc.M115.66791

A Portable Rainfall Simulator for Plot–Scale Runoff Studies

Rainfall simulators have a long history of successful use in both laboratory and field investigations. Many plot–scale simulators, however, have been difficult to operate and transport in the field, especially in remote locations where water or electricity is unavailable. This article describes a new rainfall simulator that is relatively easy to operate and transport to and from the field while maintaining critical intensity, distribution, and energy characteristics of natural rainfall. The simulator frame is constructed from lightweight aluminum pipe with a single 50 WSQ nozzle centered at a height of 3 m (9.8 ft). An operating nozzle pressure of 28 kPa (4.1 psi) yields continuous flow at an intensity of 70 mm h-1 (2.8 in. h-1 ) over a 1.5– x 2–m (4.9– x 6.6–ft) plot area with a coefficient of uniformity of 93%. Kinetic energy of the rainfall is about 25 J m-2 mm-1 (142.8 ft–lb ft-2 in.-1), approximately 87% of natural rainfall. The simulator can be easily transported by two field personnel and completely assembled or disassembled in approximately 10 min. Water usage is at a minimum as the simulator utilizes only one nozzle

The mini-CIDEX GC/IMS: Analysis of cometary ice and dust

Comets are recognized as among the most scientifically important objects in the solar system. They are presumed relics of the early primitive material in the solar nebula and are believed to have provided a general enrichment of volatiles to the inner solar system. The Cometary Coma Chemical Composition (C4) Mission, a proposed Discovery-Class Mission, will analyze materials released into the coma, providing information leading to the understanding of the chemical composition and make-up of the cometary nucleus. As one of two scientific instruments in the C4 spacecraft, an advanced and streamlined version of the Cometary Ice and Dust Experiment (CIDEX), a mini-CIDEX, will employ an X-Ray Fluorescence (XRF) spectrometer to determine bulk elemental composition of cometary dust grains and a Gas Chromatograph/Ion Mobility Spectrometer (GC/IMS) for determination of the molecular composition of dust and ices following stepwise pyrolysis and combustion. A description of the mini-CIDEX IMS will be provided as well as data from analyses conducted using the mini-CIDEX breadboard instrument

Changes in cardiovascular risk factors in relation to increasing ethnic inequalities in cardiovascular mortality:comparison of cross-sectional data in the Health Surveys for England 1999 and 2004

OBJECTIVES: Reducing disease inequalities requires risk factors to decline quickest in the most disadvantaged populations. Our objective was to assess whether this happened across the UK's ethnic groups. DESIGN: Secondary analysis of repeated but independent cross-sectional studies focusing on Health Surveys for England 1999 and 2004. SETTING: Community-based population level surveys in England. PARTICIPANTS: Seven populations from the major ethnic groups in England (2004 sample sizes): predominantly White general (6704), Irish (1153), Chinese (723), Indian (1184), Pakistani (941), Bangladeshi (899) and Black Caribbean (1067) populations. The numbers were smaller for specific variables, especially blood tests. OUTCOME MEASURES: Data on 10 established cardiovascular risk factors were extracted from published reports. Differences between 1999 and 2004 were defined a priori as occurring when the 95% CI excluded 0 (for prevalence differences), or 1 (for risk ratios) or when there was a 5% or more change (independent of CIs). RESULTS: Generally, there were reductions in smoking and blood pressure and increases in the waist–hip ratio, body mass index and diabetes. Changes between 1999 and 2004 indicated inconsistent progress and increasing inequalities. For example, total cholesterol increased in Pakistani (0.3 mmol/L) and Bangladeshi men (0.3 mmol/L), and in Pakistani (0.3 mmol/L), Bangladeshi (0.4 mmol/L) and Black Caribbean women (0.3 mmol/L). Increases in absolute risk factor levels were common, for example, in Pakistani (five risk factors), Bangladeshi (four factors) and general population women (four factors). For men, Black Caribbeans had the most (five factor) increases. The changes relative to the general population were also adverse for three risk factors in Pakistani and Black Caribbean men, four in Bangladeshi women and three in Pakistani women. CONCLUSIONS: Changes in populations with the most cardiovascular disease and diabetes did not decline the quickest. Cardiovascular screening programmes need more targeting

Cell surface IL-1α trafficking is specifically inhibited by interferon-γ, and associates with the membrane via IL-1R2 and GPI anchors.

IL-1 is a powerful cytokine that drives inflammation and modulates adaptive immunity. Both IL-1α and IL-1β are translated as proforms that require cleavage for full cytokine activity and release, while IL-1α is reported to occur as an alternative plasma membrane-associated form on many cell types. However, the existence of cell surface IL-1α (csIL-1α) is contested, how IL-1α tethers to the membrane is unknown, and signaling pathways controlling trafficking are not specified. Using a robust and fully validated system, we show that macrophages present bona fide csIL-1α after ligation of TLRs. Pro-IL-1α tethers to the plasma membrane in part through IL-1R2 or via association with a glycosylphosphatidylinositol-anchored protein, and can be cleaved, activated, and released by proteases. csIL-1α requires de novo protein synthesis and its trafficking to the plasma membrane is exquisitely sensitive to inhibition by IFN-γ, independent of expression level. We also reveal how prior csIL-1α detection could occur through inadvertent cell permeabilisation, and that senescent cells do not drive the senescent-associated secretory phenotype via csIL-1α, but rather via soluble IL-1α. We believe these data are important for determining the local or systemic context in which IL-1α can contribute to disease and/or physiological processes.Work was funded by British Heart Foundation Grants FS/13/3/30038, FS/18/19/33371 and RG/16/8/32388 to MCHC, the BHF Cambridge CRE RE/13/6/30180, and the Cambridge NIHR Biomedical Research Centr

Senescent Vascular Smooth Muscle Cells Drive Inflammation Through an Interleukin-1α-Dependent Senescence-Associated Secretory Phenotype.

OBJECTIVE: Vascular smooth muscle cells (VSMCs) that become senescent are both present within atherosclerotic plaques and thought to be important to the disease process. However, senescent VSMCs are generally considered to only contribute through inaction, with failure to proliferate resulting in VSMC- and collagen-poor unstable fibrous caps. Whether senescent VSMCs can actively contribute to atherogenic processes, such as inflammation, is unknown. APPROACH AND RESULTS: We find that senescent human VSMCs develop a proinflammatory state known as a senescence-associated secretory phenotype. Senescent human VSMCs release high levels of multiple cytokines and chemokines driven by secreted interleukin-1α acting in an autocrine manner. Consequently, the VSMC senescence-associated secretory phenotype promotes chemotaxis of mononuclear cells in vitro and in vivo. In addition, senescent VSMCs release active matrix metalloproteinase-9, secrete less collagen, upregulate multiple inflammasome components, and prime adjacent endothelial cells and VSMCs to a proadhesive and proinflammatory state. Importantly, maintaining the senescence-associated secretory phenotype places a large metabolic burden on senescent VSMCs, such that they can be selectively killed by inhibiting glucose utilization. CONCLUSIONS: Senescent VSMCs may actively contribute toward the chronic inflammation associated with atherosclerosis through the interleukin-1α-driven senescence-associated secretory phenotype and the priming of adjacent cells to a proatherosclerotic state. These data also suggest that inhibition of this potentially important source of chronic inflammation in atherosclerosis requires blockade of interleukin-1α and not interleukin-1β.This study was supported by British Heart Foundation Grants FS/09/005/26845, FS/13/3/30038 (M.C.H. Clarke), and FS/10/034/28291 (M.R. Bennett).This is the final version of the article. It first appeared from Lippincott Williams & Wilkins via http://dx.doi.org/10.1161/ATVBAHA.115.30589