The Why And How Of Food Pantry Donations: The Salem Pantry

The work done at a food pantry has become even more important during COVID-19. More people are in need and the donations that people have been giving to the pantry are helping. This project investigated how and why people are choosing to donate to the Salem Pantry. After analyzing donation databases, more people prefer donating online rather than sending a check. With more donations coming in during COVID-19, it can be presumed that people are more appreciative of how important food pantries are for those in need

Chemical-Scale Studies on the Role of a Conserved Aspartate in Preorganizing the Agonist Binding Site of the Nicotinic Acetylcholine Receptor

The nicotinic acetylcholine receptor and related Cys-loop receptors are ligand-gated ion channels that mediate fast synaptic transmission throughout the central and peripheral nervous system. A highly conserved aspartate residue (D89) that is near the agonist binding site but does not directly contact the ligand plays a critical part in receptor function. Here we probe the role of D89 using unnatural amino acid mutagenesis coupled with electrophysiology. Homology modeling implicates several hydrogen bonds involving D89. We find that no single hydrogen bond is essential to proper receptor function. Apparently, the side chain of D89 establishes a redundant network of hydrogen bonds; these bonds preorganize the agonist binding site by positioning a critical tryptophan residue that directly contacts the ligand. Earlier studies of the D89N mutant led to the proposal that a negative charge at this position is essential for receptor function. However, we find that receptors with neutral side chains at position 89 can function well, if the side chain is less perturbing than the amide of asparagine (nitro or keto groups allow function) or if a compensating backbone mutation is introduced to relieve unfavorable electrostatics

Chemical Scale Studies of the Phe-Pro Conserved Motif in the Cys Loop of Cys

The functions of two conserved residues, Phe^(135) and Pro^(136), located at the apex of the Cys loop of the nicotinic acetylcholine receptor are investigated. Both residues were substituted with natural and unnatural amino acids, focusing on the role of aromaticity at Phe^(135), backbone conformation at Pro^(136), side chain polarity and volume, and the specific interaction between the aromatic side chain and the proline. NMR spectroscopy studies of model peptides containing proline and unnatural proline analogues following a Phe show a consistent increase in the population of the cis conformer relative to peptides lacking the Phe. In the receptor, a strong interaction between the Phe and Pro residues is evident, as is a strong preference for aromaticity and hydrophobicity at the Phe site. A similar influence of hydrophobicity is observed at the proline site. In addition, across a simple homologous series of proline analogues, the results reveal a correlation between receptor function and cis bias at the proline backbone. This could suggest a significant role for the cis proline conformer at this site in receptor function

Intestinal CFTR expression alleviates meconium ileus in cystic fibrosis pigs

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Chemical-Scale Studies of Ligand-Gated Ion Channels

The studies discussed in this dissertation are aimed at the chemical-scale interactions involved in neuroreceptor structure and function. Unnatural amino acids were incorporated into several ligand-gated ion channels. Two different ionotropic glutamate receptors (iGluRs), the N-methyl-D-aspartate (NMDA) receptor and the α–amino-3-hydroxy-5-methyl- 4-isoxazolepropionic acid (AMPA) receptor were studied, along with an acetylcholine receptor - the nicotinic acetylcholine receptor (nAChR), and all were analyzed with electrophysiology–an assay of receptor function. In Chapter 2, a highly conserved tryptophan (Trp607) in the ion channel pore of the NMDA receptor was investigated for its role during extracellular Mg²⁺ block. Previous studies hypothesized that a cation-π interaction between NR2BW607 and Mg²⁺ contributed to the receptor blockade. However, our studies suggest that Trp607 is not involved in a cation-π interaction with Mg²⁺, instead it is a structural component of the pore. NR2B Trp607 acts as a steric "plug," preventing Mg²⁺ permeation through the ion channel. These studies were the first to incorporate unnatural amino acids into a glutamate receptor, extending the scope of nonsense suppression methodology to a new class of neuroreceptors. Chapter 3 describes the incorporation of unnatural amino acids into the ligand binding domain (LBD) of NMDA and AMPA receptors. Previous structural studies of AMPA receptors established the overall topology of the LBD to be a clamshell, two domains clamp down around a central cleft. Further studies utilizing agonists that induce full receptor activation and partial receptor activation demonstrate a relationship between cleft closure and agonist efficacy, which is the ability to activate a receptor. Full agonists correlate with more cleft closure than partial agonists, which induce less cleft closure. To examine this relationship, we used unnatural amino acid mutagenesis to convert an NR2-conserved tyrosine to homotyrosine and an NR1 glutamine to homoglutamine, residues designed to disrupt clamshell closure by expanding the side chain without altering its functionality. The development of our functional probe demonstrates that the clamshell closure mechanism, previously shown for AMPA receptors, likely also applies to NMDA receptors, but to different degrees in the NR1 and NR2 subunits. Finally, in Chapter 4 we use unnatural amino acids, mutagenesis, and computational simulations to probe the binding interactions that are involved in agonist selectivity at the muscle-type nicotinic acetylcholine receptor. Acetylcholine (ACh) and nicotine, both agonists for nAChRs, have a high potency for neuronal receptors. However, nicotine is a weak agonist for the muscle-type nAChRs, yet the amino acids that contribute to the binding site remain the same between both types of receptors. These studies use mutagenesis and unnatural amino acids to introduce changes in the muscle-type receptor to increase nicotine potency. Although some of the mutations increase nicotine potency, none of the mutations result in a muscle-type receptor with nicotine potency as great as the neuronal receptors. A second set of studies generated a mouse muscle homology model and used molecular dynamics to simulate movements in the receptor with and without agonist bound. These structures demonstrate the importance of a hydrogen-bonding network that contributes to the pre-organization of the aromatic box. </p

Chronicle (Paterson, NJ), Vol. 23, No. 45, Dec. 2, 1951

Local information pertaining to Paterson, N.J. and surrounding Passaic County. Issues may include events, government, business, political cartoons, engagement and marriage announcements, and birth announcements