Research over the last decade on the surfactant proteins SP‐A and SP‐D suggests roles beyond surfactant lipid homeostasis, involving their participation in innate immune defence. SP‐A and SP‐D bind ...and agglutinate an impressive array of non‐self structures, ranging from bacteria and fungi to allergens and environmental inorganic substrates. Complementing binding, SP‐A and SP‐D initiate and enhance immune cell ingestion and killing of targets. Recently, some exciting developments have extended and clarified their contributions to innate immunity. Knockout mice for SP‐A and SP‐D have been developed. The SP‐A knockout confirms that SP‐A plays a key role in defence against lung pathogens and reveals the underlying defense mechanisms that require SP‐A. These surfactant proteins have also been shown to have important roles in modulating the immune response, instructing, yet quenching, the immune reactions in the lung. The crystal structure of SP‐D plus functional studies with recombinantly altered forms of SP‐A and SP‐D has begun to characterise the structural motifs responsible for mediating their immune functions. Linkage and polymorphism analysis is explaining the role these genes may play in lung diseases and infection.
Evidence of the habitability of nearby exoplanets could be found with future space missions using the technique of nulling interferometry. A nulling interferometer selectively suppresses the glare of ...starlight while allowing the light from planets to be detected. Here we report the first demonstrations of broadband mid-infrared nulling at the level required to enable such a space mission. In three separate 6 hr measurements, mid-infrared nulls were demonstrated at a mean level less than1.0 × 10-5
1.0
×
10
-
5
using a 34% bandwidth centered at a wavelength of 10 μm. This was accomplished by “adaptive nulling,” in which a deformable mirror is tuned to minimize wavelength-dependent phase and intensity differences in the interferometer.
Phase shifters are a key component of nulling interferometry, one of the potential routes to enabling the measurement of faint exoplanet spectra. Here, three different achromatic phase shifters are ...evaluated experimentally in the mid-infrared, where such nulling interferometers may someday operate. The methods evaluated include the use of dispersive glasses, a through-focus field inversion, and field reversals on reflection from antisymmetric flat-mirror periscopes. All three approaches yielded deep, broadband, mid-infrared nulls, but the deepest broadband nulls were obtained with the periscope architecture. In the periscope system, average null depths of 4x10(-5) were obtained with a 25% bandwidth, and 2x10(-5) with a 20% bandwidth, at a central wavelength of 9.5 mum. The best short term nulls at 20% bandwidth were approximately 9x10(-6), in line with error budget predictions and the limits of the current generation of hardware.
Planetary Instrument for X-ray Lithochemistry (PIXL) is a micro-focus X-ray fluorescence spectrometer mounted on the robotic arm of NASA’s
Perseverance
rover. PIXL will acquire high spatial ...resolution observations of rock and soil chemistry, rapidly analyzing the elemental chemistry of a target surface. In 10 seconds, PIXL can use its powerful 120 μm-diameter X-ray beam to analyze a single, sand-sized grain with enough sensitivity to detect major and minor rock-forming elements, as well as many trace elements. Over a period of several hours, PIXL can autonomously raster-scan an area of the rock surface and acquire a hyperspectral map comprised of several thousand individual measured points. When correlated to a visual image acquired by PIXL’s camera, these maps reveal the distribution and abundance variations of chemical elements making up the rock, tied accurately to the physical texture and structure of the rock, at a scale comparable to a 10X magnifying geological hand lens. The many thousands of spectra in these postage stamp-sized elemental maps may be analyzed individually or summed together to create a bulk rock analysis, or subsets of spectra may be summed, quantified, analyzed, and compared using PIXLISE data analysis software. This hand lens-scale view of the petrology and geochemistry of materials at the
Perseverance
landing site will provide a valuable link between the larger, centimeter- to meter-scale observations by Mastcam-Z, RIMFAX and Supercam, and the much smaller (micron-scale) measurements that would be made on returned samples in terrestrial laboratories.
Porcine organs and lung surfactant have medically important applications in both xenotransplantation and therapy. We have started to characterize porcine lung surfactant by cloning the cDNA of ...porcine surfactant protein D (SP-D). SP-D and SP-A are important mediators in innate immune defense for the lung and possibly other mucosal surfaces. Porcine SP-D will also be an important reagent for use in existing porcine animal models for human lung infections. The complete cDNA sequence of porcine SP-D, including the 5' and 3' untranslated regions, was determined from two overlapping bacteriophage clones and by PCR cloning. Three unique features were revealed from the porcine sequence in comparison to SP-D from other previously characterized species, making porcine SP-D an intriguing species addition to the SP-D/collectin family. The collagen region contains an extra cysteine residue, which may have important structural consequences. The other two differences, a potential glycosylation site and an insertion of three amino acids, lie in the loop regions of the carbohydrate recognition domain, close to the carbohydrate binding region and thus may have functional implications. These variations were ruled out as polymorphisms or mutations by confirming the sequence at the genomic level in four different pig breeds. Porcine SP-D was shown to localize primarily to the lung and with less abundance to the duodenum, jejunum, and ileum. The genes for SP-D and SP-A were also shown to colocalize to a region of porcine chromosome 14 that is syntenic with the human and murine collectin loci.
The relationship between treatment efficacy and the pharmacokinetics (PK) and pharmacodynamics (PD) of anticancer drugs is poorly defined. 1,3-Bis(2-chloroethyl)-1-nitrosourea (BCNU) is an alkylating ...agent used in the treatment of brain and other forms of cancer. It is postulated that BCNU kills cells by forming DNA interstrand cross-links. The present study was undertaken to characterize the PK and PD of BCNU in mouse L1210 cells. L1210 cells were exposed to BCNU (0–160
μM) and analyzed for intracellular BCNU concentrations, DNA interstrand cross-links, cell cycle phase, and cytotoxicity. The half-life of BCNU in cells was ≈40
min. The maximum reduction of mitochondrial enzyme activity (maximum cell death) achieved within 24
hr after exposure to BCNU was concentration-dependent and could be described by a Hill equation. At lower concentrations, the area under the DNA interstrand cross-link–time curve linearly correlated with the maximum cell death and the area under the BCNU concentration–time curve. BCNU induced cell accumulation in the G
2/M phase of the cell cycle, which continued even after apparent completion of cross-link repair. Loss of membrane permeability was minimal (≈2%) during the first 24
hr. Thereafter, cells died exponentially over the next 9 days, primarily by necrosis. In conclusion, while cytotoxicity was concentration-dependent, an indirect relationship was found among the time-course of BCNU concentrations, DNA interstrand cross-links, and cell death. Because of the disparity between the time-scale of PK and PD, focusing only on the early events may provide limited information about the process of anticancer drug-induced cell death.
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