pH Dependence and Stoichiometry of Binding to the Fc Region of IgG by the Herpes Simplex Virus Fc Receptor gE-gI

Herpes simplex virus type 1 encodes two glycoproteins, gE and gI, that form a heterodimer on the surface of virions and infected cells. The gE-gI heterodimer has been implicated in cell-to-cell spread of virus and is a receptor for the Fc fragment of IgG. Previous studies localized the gE-gI-binding site on human IgG to a region near the interface between the CH2 and CH3 domains of Fc, which also serves as the binding site for bacterial and mammalian Fc receptors. Although there are two potential gE-gI-binding sites per Fc homodimer, only one gE-gI heterodimer binds per IgG in gel filtration experiments. Here we report production of recombinant human Fc molecules that contain zero, one, or two potential gE-gI-binding sites and use them in analytical ultracentrifugation experiments to show that two gE-gI heterodimers can bind to each Fc. Further characterization of the gE-gI interaction with Fc reveals a sharp pH dependence of binding, with KD values of ~340 and ~930 nM for the first and second binding events, respectively, at the slightly basic pH of the cell surface (pH 7.4), but undetectable binding at pH 6.0. This strongly pH-dependent interaction suggests a physiological role for gE-gI dissociation from IgG within acidic intracellular compartments, consistent with a mechanism whereby herpes simplex virus promotes intracellular degradation of anti-viral antibodies

2021-4 Innis Lecture: Return on Student Loans in Canada

This paper uses new administrative data with detailed borrower information and lengthy repayment histories from the Canada Student Loans Program (CSLP) to measure rates of return on undergraduate student loans. We document substantial heterogeneity in returns based on information available at the time loans were disbursed, including province of residence, field of study, and institution of attendance. Field of study is a particularly important determinant of rates of return, explaining 22% of the variation in predicted returns across borrowers. We explore the implications of this variation for CSLP cross-subsidization across borrowers and potential risk-based loan limits. Given the variation in ex ante predicted returns across borrowers, using all available information at the time of loan disbursement, we study the implications of potential cream-skimming of high-return borrowers by private lenders

Temperature and Drought Influence on Soybean Yield, Composition, and Seed Quality

Research studies indicate an optimum temperature for soybean photosynthesis and yield near 86°F (30°C). Although the Com Belt of the United States is one of the most productive soybean producing areas in the world, temperatures in this region are rarely centered on the ideal temperature at critical stages in soybean plant and yield development. Temperatures can vary widely within the region and fluctuate both diurnally and seasonally. The most critical stages of yield development in soybean occur when flowering is complete. Stress occurring anytime from R4 (full pod) to just after R6 (full seed), will reduce yields more than the same stress occurring at any other period of development. The period from R4.5 (late pod formation) to about R5.5 is especially critical because flowering becomes complete and cannot compensate, and because young pods and seeds are more prone to abort under stress than older pods and seeds. In addition, high temperatures during reproductive growth can alter soybean seed protein and oil composition and diminish the quality of seed used to plant the next season\u27s crop

Decentralized, Asynchronous Sensor Networks for Arctic Regions

United States Department of Homeland Security University of Alaska Anchorag

Protein-protein recognition: The neonatal Fe receptor and immunoglobulin G

The neonatal Fe receptor (FeRn) binds the Fe portion of immunoglobulin G (IgG) at the acidic pH of endosomes or the gut and releases IgG at the alkaline pH of blood. FeRn is responsible for the maternofetal transfer of IgG and for rescuing endocytosed IgG from a default degradative pathway. We investigated how FeRn interacts with IgG by constructing a heterodimeric form of the Fe (hdFc) that contains one FeRn binding site. This molecule was used to characterize the interaction between one FeRn molecule and one Fe and to determine under what conditions FeRn forms a dimer. The hdFc binds one FeRn molecule at pH 6.0 with a K_d of 80 nM. In solution and with FeRn anchored to solid supports, the heterodimeric Fe does not induce a dimer of FeRn molecules. FcRnhdFc complex crystals were obtained and the complex structure was solved to 2.8 Å resolution. Analysis of this structure refined the understanding of the mechanism of the pH-dependent binding, shed light on the role played by carbohydrates in the Fe binding, and provided insights on how to design therapeutic IgG antibodies with longer serum half-lives. The FcRn-hdFc complex in the crystal did not contain the FeRn dimer. To characterize the tendency of FeRn to form a dimer in a membrane we analyzed the tendency of the hdFc to induce cross-phosphorylation of FeRn-tyrosine kinase chimeras. We also constructed FeRn-cyan and FeRn-yellow fluorescent proteins and have analyzed the tendency of these molecules to exhibit fluorescence resonance energy transfer. As of now, neither of these analyses have lead to conclusive results. In the process of acquiring the context to appreciate the structure of the FcRn-hdFc interface, we developed a study of 171 other nonobligate protein-protein interfaces that includes an original principal component analysis of the quantifiable aspects of these interfaces

Animal lameness detection with radar sensing

Lameness is a significant problem for performance horses and farmed animals, with severe impact on animal welfare and treatment costs. Lameness is commonly diagnosed through subjective scoring methods performed by trained veterinary clinicians, but automatic methods using suitable sensors would improve efficiency and reliability. In this paper, we propose the use of radar micro-Doppler signatures for contactless and automatic identification of lameness, and present preliminary results for dairy cows, sheep, and horses. These proof-of-concept results are promising, with classification accuracy above 85% for dairy cows, around 92% for horses, and close to 99% for sheep