Hereditary hemochromatosis (HH) is a prevalent genetic disorder that results in the daily excess absorption of dietary iron. If untreated this disease leads to systemic organ failure and death. HH is caused by mutations to the gene coding for a protein called HFE, a type I transmembrane glycoprotein with a demonstrated role in regulating cellular iron homeostasis. HFE binds to the cell-surface receptor transferrin receptor (TfR), a dimeric type II transmembrane glycoprotein responsible for iron uptake into most mammalian cell types. TfR binds iron-loaded transferrin (Fe-Tf) from the blood and transports it to acidic recycling endosomes where iron is released from Fe-Tf in a TfR-facilitated process. Iron-free transferrin (apo-Tf) remains bound to TfR and is recycled to the cell surface, where apo-Tf rapidly dissociates from TfR upon exposure to the basic pH of blood. HFE and Fe-Tf can bind simultaneously to TfR to form a ternary complex, but HFE binding to TfR lowers the apparent affinity of the Fe-Tf/TfR interaction. This reduction could result from direct competition between HFE and Fe-Tf for receptor binding sites, from negative cooperativity, or both. We sought to understand the mechanism of HFE, Fe-Tf, and apo-Tf binding by TfR to help define HFE's role in iron homeostasis. We determined the binding constants for HFE, Fe-Tf, and apo-Tf to an extensive set of site-directed TfR mutants and discovered that HFE and Tf bind to an overlapping site on TfR, indicating the two proteins compete with each other for receptor binding. The mutagenesis results also identified differences in the contact points between TfR and the two forms of Tf, Fe-Tf and apo-Tf. By combining the mutations that are required for apo-Tf, but not Fe-Tf, binding we find that a highly conserved hydrophobic patch on the TfR surface is required for the receptor-mediated stimulation of iron release from Fe-Tf. From these data we propose a structure-based model for the mechanism of TfR-assisted iron release.

During development an organism undergoes many rounds of pattern formation, generating ever greater complexity with each ensuing round of cell division and specification. The instructions for executing this process are encoded in the DNA, in cis-regulatory modules that direct the expression of developmental transcription factors and signaling molecules.

A rock-plant filter, also called constructed wetland, is a term applied to a system designed to accomplish specific treatment tasks for wastewater, mimicking natural wetlands. Natural wetlands are environments where plant roots are submerged in water or saturated soil all or most of the time.

They have several unique and desirable properties. Natural wetlands allow flows to expand and contract while removing and assimilating nutrients and other contaminants. Wetlands are sometimes referred to as the purifier in the environment.

Rock-plant filters have been developed, researched and promoted to treat wastewater. These systems include areas, usually lined with impermeable materials, where wetland plants are grown in wastewater. Since about 1980, they have received
attention as a viable method for treatment of both municipal and industrial wastewaters and for remediation of contaminated sites. Wastewater supplied to these wetlands has previously been treated by wastewater ponds, extended aeration,
activated sludge, or some other method to stabilize the wastewater. The wetland provides added treatment to improve quality of the effluent by removing nutrients and reducing suspended solids.

Technological progress, human capital, and tax policies play an important role in growth.

Recent models of endogenous growth based on technological progress predict that high technological progress and growth are associated with a high relative supply of skilled workers who earn constant or relatively low wages.

Chapter 1 of this dissertation reviews recent models of endogenous growth. The 1980s, however, are associated with high technological progress, high relative supply and increasing relative wages of skilled workers.