A novel mechanism for binding of galactose-terminated glycans by the C-type carbohydrate recognition domain in blood dendritic cell antigen 2

Blood dendritic cell antigen 2 (BDCA-2; also designated CLEC4C or CD303) is uniquely expressed on plasmacytoid dendritic cells. Stimulation of BDCA-2 with antibodies leads to an anti-inflammatory response in these cells, but the natural ligands for the receptor are not known. The C-type carbohydrate recognition domain in the extracellular portion of BDCA-2 contains a signature motif typical of C-type animal lectins that bind mannose, glucose, or GlcNAc, yet it has been reported that BDCA-2 binds selectively to galactose-terminated, biantennary N-linked glycans. A combination of glycan array analysis and binding competition studies with monosaccharides and natural and synthetic oligosaccharides have been used to define the binding epitope for BDCA-2 as the trisaccharide Galβ1–3/4GlcNAcβ1–2Man. X-ray crystallography and mutagenesis studies show that mannose is ligated to the conserved Ca2+ in the primary binding site that is characteristic of C-type carbohydrate recognition domains, and the GlcNAc and galactose residues make additional interactions in a wide, shallow groove adjacent to the primary binding site. As predicted from these studies, BDCA-2 binds to IgG, which bears galactose-terminated glycans that are not commonly found attached to other serum glycoproteins. Thus, BDCA-2 has the potential to serve as a previously unrecognized immunoglobulin Fc receptor

Physical Structure of Small Wolf-Rayet Ring Nebulae

We have selected the seven most well-defined WR ring nebulae in the LMC (Br 2, Br 10, Br 13, Br 40a, Br 48, Br 52, and Br 100) to study their physical nature and evolutionary stages. New CCD imaging and echelle observations have been obtained for five of these nebulae; previous photographic imaging and echelle observations are available for the remaining two nebulae. Using the nebular dynamics and abundances, we find that the Br 13 nebula is a circumstellar bubble, and that the Br 2 nebula may represent a circumstellar bubble merging with a fossil main-sequence interstellar bubble. The nebulae around Br 10, Br 52, and Br 100 all show influence of the ambient interstellar medium. Their regular expansion patterns suggest that they still contain significant amounts of circumstellar material. Their nebular abundances would be extremely interesting, as their central stars are WC5 and WN3-4 stars whose nebular abundances have not been derived previously. Intriguing and tantalizing implications are obtained from comparisons of the LMC WR ring nebulae with ring nebulae around Galactic WR stars, Galactic LBVs, LMC LBVs, and LMC BSGs; however, these implications may be limited by small-number statistics. A SNR candidate close to Br 2 is diagnosed by its large expansion velocity and nonthermal radio emission. There is no indication that Br 2's ring nebula interacts dynamically with this SNR candidate.Comment: 20 pages, Latex (aaspp4.sty), 2 figures, accepted by the Astronomical Journal (March 99 issue

Cyclooxygenase inhibitors acetylsalicylic acid and indomethacin do not affect capsaicin-induced neurogenic inflammation in human skin

Neurogenic inflammation is evoked by neuropeptides released from primary afferent terminals and, presumably, by other secondarily released inflammatory mediators. This study examines whether prostaglandins might participate in the development of neurogenic inflammation in humans and whether cyclooxygenase inhibitors have any anti-inflammatory effect on this type of inflammation. In healthy volunteers, neurogenic inflammation was elicited by epicutaneously applied capsaicin (1 %), after systemic pretreatment with acetylsalicylic acid, or topically applied indomethacin compared to pretreatment with saline or vehicle, respectively. The extent of neurogenic inflammation was quantified by planimetry of visible flare size and recording the increase of superficial cutaneous blood flow (SCBF) with a laser Doppler flowmeter. Capsaicin-induced flare sizes and outside SCBF (both representing neurogenically evoked inflammation) were unaffected by acetylsalicylic acid or indomethacin. Only the capsaicin-induced increase; of inside SCBF was attenuated by local pretreatment with indomethacin, reflecting the participation of prostaglandins in the inflammatory response of those areas which were in direct contact with capsaicin

Supercurrent in Nb/InAs-Nanowire/Nb Josephson junctions

We report on the fabrication and measurements of planar mesoscopic Josephson junctions formed by InAs nanowires coupled to superconducting Nb terminals. The use of Si-doped InAs-nanowires with different bulk carrier concentrations allowed to tune the properties of the junctions. We have studied the junction characteristics as a function of temperature, gate voltage, and magnetic field. In junctions with high doping concentrations in the nanowire Josephson supercurrent values up to 100\,nA are found. Owing to the use of Nb as superconductor the Josephson coupling persists at temperatures up to 4K. In all junctions the critical current monotonously decreased with the magnetic field, which can be explained by a recently developed theoretical model for the proximity effect in ultra-small Josephson junctions. For the low-doped Josephson junctions a control of the critical current by varying the gate voltage has been demonstrated. We have studied conductance fluctuations in nanowires coupled to superconducting and normal metal terminals. The conductance fluctuation amplitude is found to be about 6 times larger in superconducting contacted nanowires. The enhancement of the conductance fluctuations is attributed to phase-coherent Andreev reflection as well as to the large number of phase-coherent channels due to the large superconducting gap of the Nb electrodes.Comment: 5 Figure, submitted to Journal of Applied Physic

Common Polymorphisms in Human Langerin Change Specificity for Glycan Ligands

Langerin, a C-type lectin on Langerhans cells, mediates carbohydrate-dependent uptake of pathogens in the first step of antigen presentation to the adaptive immune system. Langerin binds a diverse range of carbohydrates including high mannose structures, fucosylated blood group antigens, and glycans with terminal 6-sulfated galactose. Mutagenesis and quantitative binding assays indicate that salt bridges between the sulfate group and two lysine residues compensate for the nonoptimal binding of galactose at the primary Ca(2+) site. A commonly occurring single nucleotide polymorphism (SNP) in human langerin results in change of one of these lysine residues, Lys-313, to isoleucine. Glycan array screening reveals that this amino acid change abolishes binding to oligosaccharides with terminal 6SO(4)-Gal and enhances binding to oligosaccharides with terminal GlcNAc residues. Structural analysis shows that enhanced binding to GlcNAc may result from Ile-313 packing against the N-acetyl group. The K313I polymorphism is tightly linked to another SNP that results in the change N288D, which reduces affinity for glycan ligands by destabilizing the Ca(2+)-binding site. Langerin with Asp-288 and Ile-313 shows no binding to 6SO(4)-Gal-terminated glycans and increased binding to GlcNAc-terminated structures, but overall decreased binding to glycans. Altered langerin function in individuals with the linked N288D and K313I polymorphisms may affect susceptibility to infection by microorganisms

Variable Unidentified Emission Near 6307 AA in Eta Carinae

We have discovered a conspicuous unidentified variable feature near 6307 AA in the spectrum of Eta Carinae which is spatially unresolved from the central star and its wind (r < 200--300 AU). It is significant for two reasons: such prominent unidentified lines are now rare in this object, and this feature varies strongly and systematically. It exhibits a combination of characteristics which, so far as we know are unique in Eta Carinae's spectrum. It may provide insights into the recurrent spectroscopic events and the star's long-term brightening.Comment: 22 pages, 7 Figures, 3 Tables; Accepted PASP, appearing May 200