Substance P induces localization of MIF/α1-inhibitor-3 complexes to umbrella cells via paracellular transit through the urothelium in the rat bladder

BACKGROUND: Macrophage migration inhibitory factor (MIF) is released into the intraluminal fluid during bladder inflammation in the rat complexed to α1-inhibitor-3 (A1-I3; a rodent proteinase inhibitor in the α-macroglobulin family). The location of A1-I3 in the bladder had not been investigated. Therefore, we examined the location of A1-I3 and MIF/A1-I3 complexes in the bladder and changes due to experimental inflammation. METHODS: Anesthetized male rats had bladders removed with no treatment (intact) or were injected with Substance P (SP; s.c.; saline vehicle). After one hour intraluminal fluid was removed, bladder was excised and MIF and A1-I3 levels were determined using ELISA and/or western-blotting. MIF co-immunoprecipitation determined MIF/A1-I3 complexes in the bladder. Bladder sections were immunostained for A1-I3 and MIF/A1-I3. RESULTS: A1-I3 immunostaining was observed in interstitial spaces throughout the bladder (including submucosa) but not urothelium in intact and saline-treated rats. RT-PCR showed that the bladder does not synthesize A1-I3, therefore, A1-I3 in the interstitial space of the bladder must be plasma derived. In SP-treated rats, A1-I3 in the bladder increased and A1-I3 was observed traversing through the urothelium. Umbrella cells that do not show MIF and/or A1-I3 immunostaining in intact or saline-treated rats, showed co-localization of MIF and A1-I3 after SP-treatment. Western blotting demonstrated that in the bladder MIF formed non-covalent interactions and also binds covalently to A1-I3 to form high molecular weight MIF/A1-I3 complexes (170, 130 and 75-kDa, respectively, verified by co-immunoprecipitation). SP-induced inflammation selectively reduced 170-kDa MIF/A1-I3 in the bladder while increasing 170 and 130-kDa MIF/A1-I3 in the intraluminal fluid. CONCLUSION: A1-I3 and MIF/A1-I3 complexes are resident in bladder interstitium. During SP-induced inflammation, MIF/A1-I3 complexes are released from the bladder into the lumen. Binding of MIF/A1-I3 complexes to urothelial cells during inflammation suggests these complexes participate in the inflammatory reaction through activation of receptors for MIF and/or for A1-I3

Discovery of a 66 mas Ultracool Binary with Laser Guide Star Adaptive Optics

We present the discovery of 2MASS J21321145+1341584AB as a closely separated (0.066") very low-mass field dwarf binary resolved in the near-infrared by the Keck II Telescope using laser guide star adaptive optics. Physical association is deduced from the angular proximity of the components and constraints on their common proper motion. We have obtained a near-infrared spectrum of the binary and find that it is best described by an L5+/-0.5 primary and an L7.5+/-0.5 secondary. Model-dependent masses predict that the two components straddle the hydrogen burning limit threshold with the primary likely stellar and the secondary likely substellar. The properties of this sytem - close projected separation (1.8+/-0.3 AU) and near unity mass ratio - are consistent with previous results for very low-mass field binaries. The relatively short estimated orbital period of this system (~7-12 yr) makes it a good target for dynamical mass measurements. Interestingly, the system's angular separation is the tightest yet for any very low-mass binary published from a ground-based telescope and is the tightest binary discovered with laser guide star adaptive optics to date.Comment: 10 pages, 3 figures; accepted for publication to A

Potential effects of atmospheric collapse on Martian heat flow and application to the InSight measurements

Heat flow is an important constraint on planetary formation and evolution. It has been suggested that Martian obliquity cycles might cause periodic collapses in atmospheric pressure, leading to corresponding decreases in regolith thermal conductivity (which is controlled by gas in the pore spaces). Geothermal heat would then build up in the subsurface, potentially affecting present–day heat flow — and thus the measurements made by a heat–flow probe such as the InSight HP3 instrument. To gauge the order of magnitude of this effect, we model the diffusion of a putative heat pulse caused by thermal conductivity changes with a simple numerical scheme and compare it to the heat–flow perturbations caused by other effects. We find that an atmospheric collapse to 300 Pa in the last 40 kyr would lead to a present–day heat flow that is up to larger than the average geothermal background. Considering the InSight mission with expected error bars on the HP3 measurement, this perturbation would only be significant in the best-case scenario of full instrument deployment, completed measurement campaign, and a well–modelled surface configuration. The prospects for detecting long-term climate perturbations via spacecraft heat–flow experiments remain challenging

A Reflective Gaussian Coronagraph for ExAO: Laboratory Performance

We report laboratory results of a coronagraphic test bench to assess the intensity reduction differences between a "Gaussian" tapered focal plane coronagraphic mask and a classical hard-edged "Top Hat" function mask at Extreme Adaptive Optics (ExAO) Strehl ratios of ~94%. However, unlike a traditional coronagraph design, we insert a reflective focal plane mask at 45 degree to the optical axis. We also used an intermediate secondary mask ("Mask_2") before a final image in order to block additional mask-edge diffracted light. The test bench simulates the 8.1m Gemini North telescope. It includes one spider vane, different mask radii (r= 1.9, 3.7, 7.4 lambda/D) and two types of reflective focal plane masks (hard-edged "Top Hat" and "Gaussian" tapered profiles). In order to investigate the relative performance of these competing coronagraphic designs with regard to extra-solar planet detection sensitivity, we utilize the simulation of realistic extra-solar planet populations (Nielson et al. 2006). With an appropriate translation of our laboratory results to expected telescope performance, a "Gaussian" tapered mask radius of 3.7 lambda/D with an additional mask ("Mask_2") performs best (highest planet detection sensitivity). For a full survey with this optimal design, the simulation predicts ~30% more planets detected compared to a similar sized "Top Hat" function mask with "Mask_2." Using the best design, the point contrast ratio between the stellar PSF peak and the coronagraphic PSF at 10 lambda/D (0.4" in H band if D = 8.1m) is ~10 times higher than a classical Lyot "Top Hat" coronagraph. Hence, we find a Gaussian apodized mask with an additional blocking mask is a superior (~10x higher contrast) than use of a classical Lyot coronagraph for ExAO-like Strehls.Comment: 42 pages, 12 figures, 1 table: accepted by the Publications of the Astronomical Society of the Pacifi