The effect of lipoprotein-associated phospholipase A2 deficiency on pulmonary allergic responses in Aspergillus fumigatus sensitized mice.

BackgroundLipoprotein-associated phospholipase A2 (Lp-PLA2)/platelet-activating factor acetylhydrolase (PAF-AH) has been implicated in the pathogenesis of cardiovascular disease. A therapeutic targeting of this enzyme was challenged by the concern that increased circulating platelet activating factor (PAF) may predispose to or increase the severity of the allergic airway response. The aim of this study was to investigate whether Lp-PLA2 gene deficiency increases the risk of PAF and IgE-mediated inflammatory responses in vitro and in vivo using mouse models.MethodsLp-PLA2-/- mice were generated and back crossed to the C57BL/6 background. PAF-AH activity was measured using a hydrolysis assay in serum and bronchoalveolar lavage (BAL) samples obtained from mice. Aspergillus fumigatus (Af)-specific serum was prepared for passive allergic sensitization of mice in vivo and mast cells in vitro. β- hexosaminidase release was studied in bone marrow derived mast cells sensitized with Af-specific serum or DNP-IgE and challenged with Af or DNP, respectively. Mice were treated with lipopolysaccharide (LPS) and PAF intratracheally and studied 24 hours later. Mice were sensitized either passively or actively against Af and were studied 48 hours after a single intranasal Af challenge. Airway responsiveness to methacholine, inflammatory cell influx in the lung tissue and BAL, immunoglobulin (ELISA) and cytokine (Luminex) profiles were compared between the wild type (WT) and Lp-PLA2-/- mice.ResultsPAF-AH activity was reduced but not completely abolished in Lp-PLA2-/- serum or by in vitro treatment of serum samples with a high saturating concentration of the selective Lp-PLA2 inhibitor, SB-435495. PAF inhalation significantly enhanced airway inflammation of LPS treated WT and Lp-PLA2-/- mice to a similar extent. Sensitized WT and Lp-PLA2-/- bone-marrow derived mast cells released β-hexosaminidase following stimulation by allergen or IgE crosslinking to equivalent levels. Wild type and Lp-PLA2-/- mice responded to passive or active allergic sensitization by significant IgE production, airway inflammation and hyperresponsiveness after Af challenge. BAL cell influx was not different between these strains while IL-4, IL-5, IL-6 and eotaxin release was attenuated in Lp-PLA2-/- mice. There were no differences in the amount of total IgE levels in the Af sensitized WT and Lp-PLA2-/- mice.ConclusionsWe conclude that Lp-PLA2 deficiency in C57BL/6 mice did not result in a heightened airway inflammation or hyperresponsiveness after PAF/LPS treatment or passive or active allergic sensitization and challenge

Optimization of double pulse pumping for Ni-like Sm x-ray lasers

We report a systematic study of double pulse pumping of the Ni-like Sm x-ray laser at 73 Angstrom, currently the shortest wavelength saturated x-ray laser. It is found that the Sm x-ray laser output can change by orders of magnitude when the intensity ratio of the pumping pulses and their relative delay are varied. Optimum pumping conditions are found and interpreted in terms of a simple model. (C) 1999 American Institute of Physics. [S0021-8979(99)07102-9]

Differential involvement of Na(+),K(+)-ATPase isozymes in preimplantation development of the mouse.

Na(+),K(+)-ATPase plays an essential role in mammalian blastocoel formation (cavitation) by driving trans-epithelial sodium transport. Previously, the alpha1 and beta1 subunit isoforms of this enzyme were identified in preimplantation mouse embryos and were assumed to be responsible for this function. Here we show that mRNAs encoding an additional alpha subunit isoform (alpha3) and the remaining two beta subunit isoforms are also present in preimplantation embryos. Whereas alpha3 mRNA accumulates between the four-cell and the blastocyst stages and thus results from embryonic transcription, the same could not be demonstrated for beta2 and beta3 mRNAs. Immunoblot analyses confirmed that these subunits are present in cavitating embryos. Using confocal immunofluorescence microscopy we found that alpha1 and beta1 subunits are concentrated in the basolateral membranes of the trophectoderm while being equally distributed in plasma membranes of the inner cell mass. In contrast, alpha3, beta2, and beta3 subunits were not detected in plasma membranes. Our current assessment, therefore, is that as many as six isozymes of Na(+),K(+)-ATPase could be involved in preimplantation development although it is primarily the alpha1beta1 isozyme that is responsible for blastocoel formation. Our findings imply that the regulation of sodium transport within the preimplantation mouse embryo is more complex than had been appreciated

Supersonic strain front driven by a dense electron-hole plasma

We study coherent strain in (001) Ge generated by an ultrafast laser-initiated high density electron-hole plasma. The resultant coherent pulse is probed by time-resolved x-ray diffraction through changes in the anomalous transmission. The acoustic pulse front is driven by ambipolar diffusion of the electron-hole plasma and propagates into the crystal at supersonic speeds. Simulations of the strain including electron-phonon coupling, modified by carrier diffusion and Auger recombination, are in good agreement with the observed dynamics.Comment: 4 pages, 6 figure

Categorization of compensatory motions in transradial myoelectric prosthesis users

Background: Prosthesis users perform various compensatory motions to accommodate for the loss of the hand and wrist as well as the reduced functionality of a prosthetic hand. Objectives: Investigate different compensation strategies that are performed by prosthesis users. Study Design: Comparative analysis Methods: 20 able-bodied subjects and 4 prosthesis users performed a set of bimanual activities. Movements of the trunk and head were recorded using a motion capture system, and a digital video recorder. Clinical motion angles were calculated to assess the compensatory motions made by the prosthesis users. The video recording also assisted in visually identifying the compensations. Results: Compensatory motions by the prosthesis users were evident in the tasks performed (slicing and stirring activities) as compared to the benchmark of able-bodied subjects. Compensations took the form of a measured increase in range of motion, an observed adoption of a new posture during task execution, and pre-positioning of items in the workspace prior to initiating a given task. Conclusion: Compensatory motions were performed by prosthesis users during the selected tasks. These can be categorized into three different types of compensations

Dwarf deer of Crete.

26 pages : illustrations (some color), map ; 26 cm.Age-graded fossils of Pleistocene endemic Cretan deer (Candiacervus spp.) reveal unexpectedly high juvenile mortality similar to that reported for extant mainland ruminants, despite the fact that these deer lived in a predator-free environment and became extinct before any plausible date for human arrival. Age profiles show that deer surviving past the fawn stage were relatively long-lived for ruminants, indicating that high juvenile mortality was not an expression of their living a "fast" life. Although the effects on survivorship of such variables as fatal accidents, starvation, and disease are difficult to gauge in extinct taxa, the presence of extreme morphological variability within nominal species/ecomorphs of Candiacervus is consistent with the view that high juvenile mortality can function as a key innovation permitting rapid adaptation in insular contexts

Exoplanet Characterization and the Search for Life

Over 300 extrasolar planets (exoplanets) have been detected orbiting nearby stars. We now hope to conduct a census of all planets around nearby stars and to characterize their atmospheres and surfaces with spectroscopy. Rocky planets within their star's habitable zones have the highest priority, as these have the potential to harbor life. Our science goal is to find and characterize all nearby exoplanets; this requires that we measure the mass, orbit, and spectroscopic signature of each one at visible and infrared wavelengths. The techniques for doing this are at hand today. Within the decade we could answer long-standing questions about the evolution and nature of other planetary systems, and we could search for clues as to whether life exists elsewhere in our galactic neighborhood.Comment: 7 pages, 2 figures, submitted to Astro2010 Decadal Revie