A Novel Kappa Opioid Receptor Antagonist with Prolonged Duration of Action
Redman, Paula
The history of opioid use traces its roots back to ancient civilizations, where substanceslike the opium poppy (Papaver somniferum) were harnessed for their remarkable analgesic
properties. Today, the conventional analgesic option is opioids that target the mu opioid receptor
(MOR), however, they are associated with deleterious effects, such as the development of
dependence and respiratory depression. However, the kappa opioid receptor (KOR) subtype,
found on the surface of cells particularly in the brain and spinal cord, promotes the negative
affect of chronic pain and blockade of KOR signaling would be therapeutically desirable. KOR
antagonists including CYM53093 (i.e., Navacaprant, former BTRX-335140 and NMRA-140) are
in advanced clinical development for the treatment of severe depression, anxiety and anhedonia
but require frequent dosing for beneficial effects due to their relatively short duration of action.
This poses challenges for patient adherence and increases treatment costs. Developing longer-
acting formulations is crucial to enhance convenience, adherence, and cost-effectiveness in
managing conditions like generalized anxiety, major depressive disorder, pain and its
comorbidities. This study pharmacologically evaluated the potential of longer-acting temporal
profile for novel KOR antagonist, CYM3063, in mice.
A Novel Kappa Opioid Receptor Antagonist with Prolonged Duration of Action
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Assessing the Potential for Hemp to be Used in the Bioremediation of Soils Containing Perfluoroalkyl Substances (PFAS)
Assessing the Potential for Hemp to be Used in the Bioremediation of Soils Containing Perfluoroalkyl Substances (PFAS)
Dusza, Nicholas Bernard
Widespread industrial and commercial use of perfluoroalkyl substances (PFAS) has led to their accumulation in soil, groundwater, and freshwater supplies. The high stability of PFAS has rendered many traditional methods of remediation largely ineffective or too expensive to implement. This study seeks to quantify the efficacy of hemp as phytoremediator of soil contaminated by wastewater biosolid containing PFAS. Twenty hemp plants were cultivated using Arizona desert soil and mixed with biosolid contaminated with PFAS. The biosolid was incorporated into the soil at varying loading rates: 0%, 5%, 15%, and 30% biosolid by volume. Biosolid treatment groups consisted of five cannabis plants that were kept in a state of vegetative growth for 16 weeks. Initial soil samples were taken from the homogenized biosolid treatment mixtures before planting and compared with the final soil samples obtained from each plant to assess changes in PFAS levels. After harvest, plant tissue samples were taken from the roots, stems, and leaves for PFAS analysis. Plant growth metrics (height, stem diameter and number of axials) were recorded weekly for each plant. The plants grown in 5% biosolid by volume exhibited the greatest height and largest average stem diameter. The plants grown in 15% biosolid mixture appeared to be the healthiest and had greater biomass. The experiment unveiled significant translocation of PFOA and PFBS into various regions of the plants in all biosolid treatments. Specifically, within treatment #1 and treatment #2, 20.56% and 49.06% of the PFOA from the initial soil samples were translocated into the roots of plants, respectively. The types of PFAS that tend to be taken up by the plants are water soluble and tend to leach through soil. PFOS was found to be filtered out of samples by solid phase extraction ENV cartridges and were not translocated into the plants.
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Characterization of Small Molecule Inhibitors of CLKs and DYRKs
Characterization of Small Molecule Inhibitors of CLKs and DYRKs
Gonzalez, Lucia
Colorectal cancer (CRC) used to be known as a disease of old age, but now it is becoming a concern for younger adults. Researchers are unsure why, but they believe it may be due to environmental factors that lead to genetic changes in the colonic epithelium. These genetic changes affect essential signaling pathways, making them a crucial research focus. The Wnt signaling pathway is significant in maintaining digestive tract homeostasis but is often dysregulated in cancer. For this reason, researchers are working to identify proteins that affect Wnt signaling and target them with inhibitors. The CLK and DYRK kinase families are a group of proteins closely linked to the Wnt signaling pathway and implicated in disease. In this study, I tested 107 novel small molecules that are CLK/DYRK inhibitors in a dose-response curve with human colonic epithelial cells (HCECs). From this data, we identified six top compounds that were tested further in a cell viability assay to determine their efficacy against cancer cells. We also immunoblotted for CLKs' substrate to understand how the compounds work and obtained pharmacokinetic data to understand their biomechanics. Ultimately, two promising compounds emerged as potential candidates for further organoid profiling – DYR726 and DYR895. We are especially excited for DYR895 to be FDA-approved soon, but we will also further assess DYR726
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MATHEMATICS, SUBJECTIVITY AND STANDPOINT THEORY: A FEMINIST CRITIQUE OF THE MATHEMATICAL UNIVERSE HYPOTHESIS
MATHEMATICS, SUBJECTIVITY AND STANDPOINT THEORY: A FEMINIST CRITIQUE OF THE MATHEMATICAL UNIVERSE HYPOTHESIS
Della Valle, Brianna Salud Rose
Max Tegmark states in his Mathematical Universe Hypothesis that the external physical world is a mathematical structure, and proposes a supporting reality model split into three parts: external reality, consensus reality and internal reality. This reality model raises problems for phenomenological and feminist philosophies. These problems fall under the overall concern that Tegmark's reality model obfuscates human experience generally, and the lives of historically marginalized groups more specifically. This concern will initially be addressed by Husserlian phenomenology by proposing that a more rigorous reality model must take lived experience seriously. The concern will be further addressed by feminist standpoint theory which pushes the Husserlian critique into the realm of socially-situated marginalized lives.
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