Mechanism for Multiple Ligand Recognition by the Human Transferrin Receptor

Transferrin receptor 1 (TfR) plays a critical role in cellular iron import for most higher organisms. Cell surface TfR binds to circulating iron-loaded transferrin (Fe-Tf) and transports it to acidic endosomes, where low pH promotes iron to dissociate from transferrin (Tf) in a TfR-assisted process. The iron-free form of Tf (apo-Tf) remains bound to TfR and is recycled to the cell surface, where the complex dissociates upon exposure to the slightly basic pH of the blood. Fe-Tf competes for binding to TfR with HFE, the protein mutated in the iron-overload disease hereditary hemochromatosis. We used a quantitative surface plasmon resonance assay to determine the binding affinities of an extensive set of site-directed TfR mutants to HFE and Fe-Tf at pH 7.4 and to apo-Tf at pH 6.3. These results confirm the previous finding that Fe-Tf and HFE compete for the receptor by binding to an overlapping site on the TfR helical domain. Spatially distant mutations in the TfR protease-like domain affect binding of Fe-Tf, but not iron-loaded Tf C-lobe, apo-Tf, or HFE, and mutations at the edge of the TfR helical domain affect binding of apo-Tf, but not Fe-Tf or HFE. The binding data presented here reveal the binding footprints on TfR for Fe-Tf and apo-Tf. These data support a model in which the Tf C-lobe contacts the TfR helical domain and the Tf N-lobe contacts the base of the TfR protease-like domain. The differential effects of some TfR mutations on binding to Fe-Tf and apo-Tf suggest differences in the contact points between TfR and the two forms of Tf that could be caused by pH-dependent conformational changes in Tf, TfR, or both. From these data, we propose a structure-based model for the mechanism of TfR-assisted iron release from Fe-Tf

Characterization and cloning of fasciclin I and fasciclin II glycoproteins in the grasshopper

Monoclonal antibodies were previously used to identify two glycoproteins, called fasciclin I and II (70 and 95 kDa, respectively), which are expressed on different subsets of axon fascicles in the grasshopper (Schistocerca americana) embryo. Here the monoclonal antibodies were used to purify these two membrane-associated glycoproteins for further characterization. Fasciclin II appears to be an integral membrane protein, where fasciclin I is an extrinsic membrane protein. The amino acid sequences of the amino terminus and fragments of both proteins were determined. Using synthetic oligonucleotide probes and antibody screening, we isolated genomic and cDNA clones. Partial DNA sequences of these clones indicate that they encode fasciclins I and II

FUSE Measurements of Far Ultraviolet Extinction. I. Galactic Sight Lines

We present extinction curves that include data down to far ultraviolet wavelengths (FUV; 1050 - 1200 A) for nine Galactic sight lines. The FUV extinction was measured using data from the Far Ultraviolet Spectroscopic Explorer. The sight lines were chosen for their unusual extinction properties in the infrared through the ultraviolet; that they probe a wide range of dust environments is evidenced by the large spread in their measured ratios of total-to-selective extinction, R_V = 2.43 - 3.81. We find that extrapolation of the Fitzpatrick & Massa relationship from the ultraviolet appears to be a good predictor of the FUV extinction behavior. We find that predictions of the FUV extinction based upon the Cardelli, Clayton & Mathis (CCM) dependence on R_V give mixed results. For the seven extinction curves well represented by CCM in the infrared through ultraviolet, the FUV extinction is well predicted in three sight lines, over-predicted in two sight lines, and under-predicted in 2 sight lines. A Maximum Entropy Method analysis using a simple three component grain model shows that seven of the nine sight lines in the study require a larger fraction of grain materials to be in dust when FUV extinction is included in the models. Most of the added grain material is in the form of small (radii < 200 A) grains.Comment: Accepted for publication in the Astrophysical Journal. 31 pages with 7 figure

Crystal Structure of the Hemochromatosis Protein HFE and Characterization of Its Interaction with Transferrin Receptor

AbstractHFE is an MHC-related protein that is mutated in the iron-overload disease hereditary hemochromatosis. HFE binds to transferrin receptor (TfR) and reduces its affinity for iron-loaded transferrin, implicating HFE in iron metabolism. The 2.6 Å crystal structure of HFE reveals the locations of hemochromatosis mutations and a patch of histidines that could be involved in pH-dependent interactions. We also demonstrate that soluble TfR and HFE bind tightly at the basic pH of the cell surface, but not at the acidic pH of intracellular vesicles. TfR:HFE stoichiometry (2:1) differs from TfR:transferrin stoichiometry (2:2), implying a different mode of binding for HFE and transferrin to TfR, consistent with our demonstration that HFE, transferrin, and TfR form a ternary complex

The Role of Polycyclic Aromatic Hydrocarbons in Ultraviolet Extinction. I. Probing small molecular PAHs

We have obtained new STIS/HST spectra to search for structure in the ultraviolet interstellar extinction curve, with particular emphasis on a search for absorption features produced by polycyclic aromatic hydrocarbons (PAHs). The presence of these molecules in the interstellar medium has been postulated to explain the infrared emission features seen in the 3-13 $\mu$m spectra of numerous sources. UV spectra are uniquely capable of identifying specific PAH molecules. We obtained high S/N UV spectra of stars which are significantly more reddened than those observed in previous studies. These data put limits on the role of small (30-50 carbon atoms) PAHs in UV extinction and call for further observations to probe the role of larger PAHs. PAHs are of importance because of their ubiquity and high abundance inferred from the infrared data and also because they may link the molecular and dust phases of the interstellar medium. A presence or absence of ultraviolet absorption bands due to PAHs could be a definitive test of this hypothesis. We should be able to detect a 20 \AA wide feature down to a 3$\sigma$ limit of $\sim$0.02 A$_V$. No such absorption features are seen other than the well-known 2175 \AA bump.Comment: 16 pages, 3 figure, ApJ in pres

Quantifying full phenological event distributions reveals simultaneous advances, temporal stability and delays in spring and autumn migration timing in long-distance migratory birds

Acknowledgements We thank all Fair Isle Bird Observatory staff and volunteers for help with data collection and acknowledge the foresight of George Waterston and Ken Williamson in instigating the observatory and census methodology. We thank all current and previous directors of Fair Isle Bird Observatory Trust for their contributions, particularly Dave Okill and Mike Wood for their stalwart support for the long-term data collection and for the current analyses. Dawn Balmer and Ian Newton provided helpful guidance on manuscript drafts. We thank Ally Phillimore and two anonymous referees for helpful comments. This study would have been impossible without the Fair Isle community's invaluable support and patience over many decades, which is very gratefully acknowledged. WTSM and JMR designed and undertook analyses, wrote the paper and contributed to data collection and compilation, MB contributed to analysis and editing, all other authors oversaw and undertook data collection and compilation and contributed to editing.Peer reviewedPostprin

Hydrothermal venting in magma deserts : the ultraslow-spreading Gakkel and Southwest Indian Ridges

Author Posting. © American Geophysical Union, 2004. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geochemistry Geophysics Geosystems 5 (2004): Q08002, doi:10.1029/2004GC000712.Detailed hydrothermal surveys over ridges with spreading rates of 50–150 mm/yr have found a linear relation between spreading rate and the spatial frequency of hydrothermal venting, but the validity of this relation at slow and ultraslow ridges is unproved. Here we compare hydrothermal plume surveys along three sections of the Gakkel Ridge (Arctic Ocean) and the Southwest Indian Ridge (SWIR) to determine if hydrothermal activity is similarly distributed among these ultraslow ridge sections and if these distributions follow the hypothesized linear trend derived from surveys along fast ridges. Along the Gakkel Ridge, most apparent vent sites occur on volcanic highs, and the extraordinarily weak vertical density gradient of the deep Arctic permits plumes to rise above the axial bathymetry. Individual plumes can thus be extensively dispersed along axis, to distances >200 km, and ∼75% of the total axial length surveyed is overlain by plumes. Detailed mapping of these plumes points to only 9–10 active sites in 850 km, however, yielding a site frequency F s , sites/100 km of ridge length, of 1.1–1.2. Plumes detected along the SWIR are considerably less extensive for two reasons: an apparent paucity of active vent fields on volcanic highs and a normal deep-ocean density gradient that prevents extended plume rise. Along a western SWIR section (10°–23°E) we identify 3–8 sites, so F s = 0.3–0.8; along a previously surveyed 440 km section of the eastern SWIR (58°–66°E), 6 sites yield F s = 1.3. Plotting spreading rate (us) versus F s, the ultraslow ridges and eight other ridge sections, spanning the global range of spreading rate, establish a robust linear trend (F s = 0.98 + 0.015us), implying that the long-term heat supply is the first-order control on the global distribution of hydrothermal activity. Normalizing F s to the delivery rate of basaltic magma suggests that ultraslow ridges are several times more efficient than faster-spreading ridges in supporting active vent fields. This increased efficiency could derive from some combination of three-dimensional magma focusing at volcanic centers, deep mining of heat from gabbroic intrusions and direct cooling of the upper mantle, and nonmagmatic heat supplied by exothermic serpentinization.This research was partially supported the NOAA VENTS Program. P.J.M. and H.J.B.D. gratefully acknowledge NSF grant OPP 9911795 for support of the AMORE Expedition; P.J.M. and E.T.B. acknowledge NSF grant OPP 0107767 and the VENTS Program for development and construction of MAPRs for use in ice-covered seas. H.J.B.D. acknowledges NSF grant OCE-9907630 for support of SWIR studies. J.E.S. was supported by Deutsche Forschungsgemeinschaft grant SN15/2

Factors Affecting Bait Site Visitation: Area of Influence of Baits

ABSTRACT Baiting is a fundamental strategy for the global management of wild pigs (Sus scrofa); however, little information exists on how anthropogenic bait affects wild pig movements on a landscape. We investigated factors that are important in determining the spatial area of attraction for wild pigs to bait (‘area of influence’ of a bait site) using data from Global Positioning System (GPS) collars and locations of bait sites. We monitored movements of wild pigs in 2 distinct study areas in the United States from February to September 2016 and used locational data using GPS collars to analyze the influence of habitat quality (dependent on site), home range size, number of bait sites in the home range, distance to a bait site, and sex in relation to movement in time and space. We determined the average area of influence by calculating the area of a circle with the radius as the average maximum distance travelled by wild pigs to reach a bait site. The average area of influence for our bait sites was 6.7 km2 (or a radius of approximately 1.5 km), suggesting a bait spacing of approximately 1.5 km would be adequate to capture visitation by most wild pigs and a spacing of 3 km could allow substantial visitation while minimizing redundant effort depending on the spatial structure of the populations. Eighty percent of wild pigs first visited bait sites within 8.9 days after bait deployment; and they visited earlier when their home range size was larger. As the number of bait sites in an individual’s home range increased, individual pigs visited more bait sites, and the probability of a visit increased dramatically up to approximately 5 bait sites and much less thereafter. Wild pigs travelled farther distances to visit bait sites in lower quality habitat. Our results support the hypothesis that habitat quality can mediate the efficacy of baiting programs for wildlife by influencing their movement patterns and motivation to use anthropogenic resources. Our results suggest wild pigs will travel extensively within their home range to visit bait sites, and that in lower quality habitat, most animals will find bait sites more quickly. Determining the area of influence of bait sites can increase the efficacy of planning and monitoring management programs. Our study provides new information to help managers plan baiting designs to attract the greatest number of pigs

Positivity of the English language

Over the last million years, human language has emerged and evolved as a fundamental instrument of social communication and semiotic representation. People use language in part to convey emotional information, leading to the central and contingent questions: (1) What is the emotional spectrum of natural language? and (2) Are natural languages neutrally, positively, or negatively biased? Here, we report that the human-perceived positivity of over 10,000 of the most frequently used English words exhibits a clear positive bias. More deeply, we characterize and quantify distributions of word positivity for four large and distinct corpora, demonstrating that their form is broadly invariant with respect to frequency of word use.Comment: Manuscript: 9 pages, 3 tables, 5 figures; Supplementary Information: 12 pages, 3 tables, 8 figure

The Diffuse Interstellar Bands: A Major Problem in Astronomical Spectroscopy

A critical review of the very long-standing problem of the diffuse interstellar bands is presented with emphasis on spectroscopic aspects of observational, modelling and laboratory-based research. Some research themes and ideas that could be explored theoretically and experimentally are discussed. The article is based on the Journal of Molecular Spectroscopy Review Lecture presented at the 60th Ohio State University International Symposium on Molecular Spectroscopy, June 2005