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A Novel Positive Allosteric Modulator of GluN1/3 NMDA Receptors
No full textThe GluN3-containing (GluN1/3) N-methyl-D-aspartate (NMDA) receptors are glycine activated ligand-gated ion channels that are members of the family of excitatory ionotropic glutamate receptors. Compared to the glycine/glutamate-activated GluN2- containing NMDA receptors (GluN1/2), which have been extensively studied, the GluN1/3 receptors are poorly understood, but are implicated in neuronal processes related to synaptic maturation and plasticity. GluN1/3 receptors are also implicated in a variety of neurological diseases. In addition to their poor understanding, we lack proper pharmacological tools for the study and modulation of these GluN1/3 receptors. In this study, we evaluate the activity and mechanism of action for AIMS-129 as a novel positive allosteric modulator (PAM) of GluN1/3A and GluN1/3B receptors, with EC50 values of 15 μM and 18 µM, respectively. AIMS-129 maximally potentiates GluN1/3A and GluN1/3B receptors to 214% and 479%, respectively, compared to responses from glycine alone. AIMS-129 stabilizes the glycine-bound, active conformation of GluN1/3 receptors and slows receptor deactivation time. AIMS-129 does not have the capability to act as an agonist and does not act competitively with glycine or D-serine agonists. Thus, AIMS-129 is classified as the first compound in a novel class of GluN3-selective PAMs and provides a new pharmacological compound that will facilitate future studies of GluN1/3 receptors and their physiological roles in normal brain function and disease
On Creating Bog Bodies: The Effects of pH Value on DNA Decomposition in a Bog Environment
No full textBog bodies have been a consistent area of interest in both archaeology and biological anthropology, due to their high rates of physical preservation. While there are many physical analyses that have been done on these remains, DNA analysis is lacking. Most studies focus on changes to the remains themselves or attempt to determine why they were placed in a bog. This study aims to examine the effects of pH level on the breakdown of DNA on remains placed inside a bog along with any larger differences in the preservation of the remains. The results of this study seem to point to a pH of four or five being ideal for DNA preservation, while a pH of six provides the best physical preservation. This provides a good starting point for future research to truly look at the variability that occurs. Out of all samples taken, the teeth were shown to be the best area to sample, when available. If they are not available, a skeletal sample should be used in its place. This is a preliminary research study, so while the data is a useful starting point, this study needs to be redone with more samples and different proxies to draw a more accurate conclusion about how pH affects DNA breakdown in bog bodies. This should be paired with a stronger focus on testing bogs where actual sets of remains were found to pair with any data found in future studies
