Correcting Glucose-6-Phosphate Dehydrogenase Deficiency With A Small-Molecule Activator, 2018 Stanford University
Correcting Glucose-6-Phosphate Dehydrogenase Deficiency With A Small-Molecule Activator, Sunhee Hwang, Karen Mruk, Simin Rahighi, Andrew G. Raub, Che-Hong Chen, Lisa E. Dorn, Naoki Horikoshi, Soichi Wakatsuki, James K. Chen, Daria Mochly-Rosen
Pharmacy Faculty Articles and Research
Glucose-6-phosphate dehydrogenase (G6PD) deficiency, one of the most common human genetic enzymopathies, is caused by over 160 different point mutations and contributes to the severity of many acute and chronic diseases associated with oxidative stress, including hemolytic anemia and bilirubin-induced neurological damage particularly in newborns. As no medications are available to treat G6PD deficiency, here we seek to identify a small molecule that corrects it. Crystallographic study and mutagenesis analysis identify the structural and functional defect of one common mutant (Canton, R459L). Using high-throughput screening, we subsequently identify AG1, a small molecule that increases the activity of the wild-type, the ...
30-Day Oral Acetaminophen Tolerance In Adult Horses, 2018 Augustana College, Rock Island Illinois
30-Day Oral Acetaminophen Tolerance In Adult Horses, Sarah E. Foreman
Celebration of Learning
There are no controlled studies of acetaminophen toxicity in horses. The objective was to test the hypotheses that oral acetaminophen administered at a dosage 25% higher than that sometimes used in horses would result in measurable hepatic toxicity as seen in humans and other species. Six healthy adult horses were administered 25 mg/kg acetaminophen powder in corn syrup twice daily for 30 days. Three other horses served as negative controls receiving only corn syrup. Jugular venous blood samples were obtained on days 7 and 1 before treatment; on treatment days 1, 2, 5, 8, 12, 15, 19, 22, 26 ...
Engineered Exosomes For Delivery Of Therapeutic Sirnas To Neurons, 2018 University of Massachusetts Medical School
Engineered Exosomes For Delivery Of Therapeutic Sirnas To Neurons, Reka A. Haraszti
GSBS Dissertations and Theses
Extracellular vesicles (EVs), exosomes and microvesicles, transfer endogenous RNAs between neurons over short and long distances. We have explored EVs for siRNA delivery to brain. (1) We optimized siRNA chemical modifications and siRNA conjugation to lipids for EV-mediated delivery. (2) We developed a GMP-compatible, scalable method to manufacture active EVs in bulk. (3) We characterized lipid and protein content of EVs in detail. (4) We established how protein and lipid composition relates to siRNA delivering activity of EVs, and we reverse engineered natural exosomes (small EVs) into artificial exosomes based on these data.
We established that cholesterol-conjugated siRNAs passively associate ...
Treatment Of Opioid Dependence And Overdose, 2018 University of Wyoming
Treatment Of Opioid Dependence And Overdose, Jessi Jeffries
Honors Theses AY 17/18
Every day in America, 90 individuals die from overdosing on prescription pain relievers or synthetic opioids. From 1999 to 2015, American deaths from opioid drug overdoses increased from 8,048 to 33,091 (National Institute on Drug Abuse, 2017). Approximately two million Americans in 2015 abused prescription pain relievers, which increased from 2014. Opioid receptors reside in the reward pathway of the brain, releasing the neurotransmitter dopamine, providing users with euphoria and analgesia. Long term drug use induces chronic constipation, drug tolerance, immune suppression, hormonal changes, and increased sensitivity to pain (Dennis, B., Naji, L., et al., 2014). Opioid use ...
Linear Ubiquitin Chain-Binding Domains, 2018 Vienna BioCenter
Linear Ubiquitin Chain-Binding Domains, Lilian Fennell, Simin Rahighi, Fumiyo Ikeda
Pharmacy Faculty Articles and Research
Ubiquitin modification (ubiquitination) of target proteins can vary with respect to chain lengths, linkage type, and chain forms, such as homologous, mixed, and branched ubiquitin chains. Thus, ubiquitination can generate multiple unique surfaces on a target protein substrate. Ubiquitin‐binding domains (UBDs) recognize ubiquitinated substrates, by specifically binding to these unique surfaces, modulate the formation of cellular signaling complexes and regulate downstream signaling cascades. Among the eight different homotypic chain types, Met1‐linked (also termed linear) chains are the only chains in which linkage occurs on a non‐Lys residue of ubiquitin. Linear ubiquitin chains have been implicated in immune ...
Factors Involved In Suppression Of Human Vγ9vδ2 T-Lymphocytes And Impact Of Checkpoint Blockades On The Effector Functions Of Vγ9vδ2 T-Lymphocytes, Minji Choi, Andrew Wiemer, Andrea Hubbard, Brian Aneskievich
University Scholar Projects
Chronic antigenic stimulation leads to T cell exhaustion, which drastically dampens T cell effector functions. Upon exhaustion, T cells progressively lose their proliferative capacity, cytokine production, and cytotoxic effector functions against tumors. T cell exhaustion involves programmed cell death-1 (PD-1), which is an inhibitory co-stimulation receptor. Limited scope of studies has been done regarding impact of PD-1 expression on the effector functions of γδ T cells. In this study, we investigated expression of PD-1 and its impact on effector functions of human γδ T cells. When γδ T cells were stimulated with phosphoantigens (HMBPP and POM2-C-HMBP) and analyzed ...
Donated Chemical Probes For Open Science, 2018 Goethe University
Donated Chemical Probes For Open Science, Susanne Muller, Paul R. Thompson, Anke Mueller-Fahrnow
Open Access Articles
Potent, selective and broadly characterized small molecule modulators of protein function (chemical probes) are powerful research reagents. The pharmaceutical industry has generated many high-quality chemical probes and several of these have been made available to academia. However, probe-associated data and control compounds, such as inactive structurally related molecules and their associated data, are generally not accessible. The lack of data and guidance makes it difficult for researchers to decide which chemical tools to choose. Several pharmaceutical companies (AbbVie, Bayer, Boehringer Ingelheim, Janssen, MSD, Pfizer, and Takeda) have therefore entered into a pre-competitive collaboration to make available a large number of ...
Marijuana And The Teenage Brain: Public Health Impact, 2018 University of Vermont
Marijuana And The Teenage Brain: Public Health Impact, Katie C. Warther
Family Medicine Clerkship Student Projects
This project explores the neurobiological impact of teenage marijuana use, and the ways that public health interventions can help educate adolescents and delay the onset of use.
Characterization Of A Ulk1 Agonist, 2018 University of Iowa
Characterization Of A Ulk1 Agonist, Michael Garneau
University of Iowa Honors Theses
The purpose of this project was to identify an agonist of autophagy. The agonist had to work specifically through increasing the expression level of ULK1 within the cell. ULK1 was used as the main marker of autophagy as it has an established role in the formation of the autophagosome, a step that is known to be crucial in the autophagy process, especially in the degradation of mitochondria. Autophagy is a cellular process that serves to breakdown and recycle cellular components that are malfunctioning or collecting above a useful level. Specifically, autophagy’s role in the degradation of poorly functioning mitochondria ...
Body Composition And Physical Function During Chemotherapy For Metastatic Breast Cancer: A Pilot Observation Study., Amelia Bandera
Breast cancer (BC) is one of the most studied malignancies in the world, and for good reason; it affects 1 in every 8 women in Australia, is the most common form of cancer amongst women, and is considered one of Australia’s largest health burdens. In Australia, early-stage BC 5-year survival rates are approximately 90%; however, 1 in 20 women whose disease is confined to the breast, and 1 in 6 women whose BC has reached adjacent tissue, will eventually progress to metastatic disease. Five-year survival rates of advanced disease drop to only 40% in Australia. Despite the abundance of ...
Analysis Of The Proposed Tpp-Related Patent Linkage System In Taiwan, 2017 National Chengchi University
Analysis Of The Proposed Tpp-Related Patent Linkage System In Taiwan, Ping-Hsun Chen
Journal of Law and Health
The Trans-Pacific Partnership (TPP) Agreement mandates member states to implement a patent linkage system vested in Article 18.53. To successfully join the TPP Agreement, Taiwan has begun the legislation of a patent linkage system by proposing an amendment for the Pharmaceutical Affairs Act. Article 18.53 requires a member either to adopt a notification mechanism under Paragraph 1 or to stay the issuance of marketing approval under Paragraph 2. But, Taiwan’s proposal includes both measures. Taiwan’ patent linkage system allows a pioneer drug company to register patents claiming (a) a material; (b) a combination or formula; or (c ...
Intratracheal Instillation Of Cerium Oxide Nanoparticles Induces Hepatic Toxicity In Male Sprague-Dawley Rats, Siva Krishna Nalabotu, Madhukar Babu Kolli, William E. Triest, Jane Y. Ma, Nandini Dpk Manne, Anjaiah Katta, Hari S. Addagarla, Kevin M. Rice, Eric R. Blough
Background: Cerium oxide (CeO2) nanoparticles have been posited to have both beneficial and toxic effects on biological systems. Herein, we examine if a single intratracheal instillation of CeO2 nanoparticles is associated with systemic toxicity in male Sprague-Dawley rats. Methods and results: Compared with control animals, CeO2 nanoparticle exposure was associated with increased liver ceria levels, elevations in serum alanine transaminase levels, reduced albumin levels, a diminished sodium-potassium ratio, and decreased serum triglyceride levels (P < 0.05). Consistent with these data, rats exposed to CeO2nanoparticles also exhibited reductions in liver weight (P < 0.05) and dose-dependent hydropic degeneration, hepatocyte enlargement, sinusoidal ...
Cytotoxicity Of Platinum Anticancer Drugs In Mammalian Cell Lines Of Metastatic Cancer, 2017 Western Kentucky University
Cytotoxicity Of Platinum Anticancer Drugs In Mammalian Cell Lines Of Metastatic Cancer, Hosannah Evie
Honors College Capstone Experience/Thesis Projects
With the invention of advanced technology, focus has been put on understanding and looking for potential cures for many diseases, one of which is cancer. The difference in the leaving and non-leaving ligands of the FDA approved cancer drugs contributes to the differential cell specific cytotoxic effects. These drugs such as oxaliplatin approved for colorectal cancer, cisplatin approved for testicular cancer, and their analogs were used to treat different cancer cell lines in an MTT assay. This project aims to determine how changing the molecular shape of these compounds affects their uptake and toxicity into different cell lines. The assay ...
Structure Activity Relationship Studies Of Novel Diarylpentanoid Analogs Targeting The Androgen Receptor In Prostate Cancer Cells, Haili Coffin, Marco Bisoffi
Student Research Day Abstracts and Posters
The development of prostate cancer (PCa) relies strongly on the activation of the androgen receptor (AR) signaling pathway by its natural ligand dihydrotestosterone. Furthermore, PCa progression to metastatic disease represents oncogene addiction to AR activity. Androgen ablation therapy is thus a mainstay therapy against this disease, but the development of ligand-independent AR activation and persisting AR expression eventually leads to castration resistant PCa (CRPC). Therefore, down-regulation of AR expression in PCa cells may be an effective therapeutic modality. The diarylpentanoid ca27 has previously been shown to down-regulate AR expression by an unknown mechanism of action. The present work represents a ...
A Review Of Ankylosing Spondylitis, 2017 Department of Biology and Chemistry
A Review Of Ankylosing Spondylitis, Hannah L. Owen
Senior Honors Theses
Ankylosing spondylitis (AS) is a systemic autoimmune disorder that induces ankylosis of the spine (fusion of the vertebrae at their various joints) and inflammatory arthritis of peripheral joints among other symptoms. Overexpression of cytokines, the presence of genetic mutations not exclusive to the human leucocyte antigen (HLA)-B27 region, and environmental factors all have large roles in the progressive development of AS. Although a definitive pathology continues to be sought after, researchers believe the adaptive immune system in AS patients attacks fibrocartilaginous entheses (supportive connective tissue between bone and attached structures like tendon, ligament, and fascia).
AS markedly reduces proper ...
Elucidating The Effects Of Metabolic State On Nanoparticle Distribution In Mice And In Vitro Uptake, 2016 University of Tennessee, Knoxville
Elucidating The Effects Of Metabolic State On Nanoparticle Distribution In Mice And In Vitro Uptake, Kevin James Quigley
Since almost 70% of the U.S. population over 20 years old is overweight and 30% is obese, with much of the western world following suit, many patients that will potentially be administered circulating nanoparticles designed to localize to tumors and avoid non-target areas will have significant amounts of white adipose tissue (WAT), enlarged livers, and additional metabolic complications such as type 2 diabetes. However, studies on nanoparticle biodistribution and efficacy take place almost without exception in lean rodents with healthy metabolic states. In this work, I determined the biodistribution of model nanoparticles – neutral filomicelles and polystyrene spheres both carrying ...
Adoption Of Perioperative Lidocaine Infusion For The Reduction Of Postoperative Pain, 2016 University of Southern Mississippi
Adoption Of Perioperative Lidocaine Infusion For The Reduction Of Postoperative Pain, Brandon Scott Figueiredo
Laparoscopic capability provides numerous benefits to patients requiring abdominal surgical procedures. However, the use of these techniques has presented the anesthesia provider with a unique set of challenges in terms of perioperative management and postoperative pain reduction. No standardized method has existed to reduce postoperative pain and improve recovery following these procedures. There were three primary goals of this project. The first goal was to conduct a meta-analysis of randomized controlled trials to determine the benefit of the use of intravenous lidocaine infusions to reduce postoperative pain in laparoscopic abdominal surgery. Twelve articles were included in the meta-analysis that pertained ...
The Role Of Nicotine, A7 Nicotinic Acetylcholine Receptors And Extracellular Matrix Remodeling In Pulmonary Fibrosis., 2016 University of Louisville
The Role Of Nicotine, A7 Nicotinic Acetylcholine Receptors And Extracellular Matrix Remodeling In Pulmonary Fibrosis., Glenn Ward Vicary
Electronic Theses and Dissertations
The median survival for idiopathic pulmonary fibrosis (IPF) patients from diagnosis is a dismal 3 years. This condition is characterized by pulmonary fibroproliferation and excess production and disordered deposition of extracellular matrix (ECM) proteins resulting in obliteration of the original tissue architecture, loss of lung function and eventual death due to respiratory failure. The main hindrance to the development of effective treatments against pulmonary fibrosis is the late detection of its progression and is often of unknown cause. Tobacco smoke represents the most important environmental factor linked to the development of pulmonary fibrosis, with over 60% of IPF patients current ...
Structural Dichotomy Of The Mind; The Role Of Sexual Neuromodulators, 2016 Carol Davila University, Department of Surgery and Psychiatry
Structural Dichotomy Of The Mind; The Role Of Sexual Neuromodulators, Ion G. Motofei, David L. Rowland
Journal of Mind and Medical Sciences
The mind (mental function) and sexuality represent two distinct environmental functions, but which are supported within the brain by a common (somatic-autonomic) neurobiological substrate. As a consequence, mental function takes on autonomic characteristics from the sexual-autonomic system (like autonomy, duality), while sexual function takes on features from mental functioning (such as lateralization). In this paper we discuss the lateralized action of two classes of sexual neuromodulators: hormones and pheromones. This process of lateralization is assimilated with the structural dichotomy of the mind.
A relatively similar process but related to informational dichotomy of the mind will be presented in a forthcoming ...
Nanofabrication And Spectroscopy Of Magnetic Nanostructures Using A Focused Ion Beam, Ali Hadjikhani
FIU Electronic Theses and Dissertations
This research used a focused ion beam in order to fabricate record small nano-magnetic structures, investigate the properties of magnetic materials in the rarely studied range of nanometer size, and exploit their extraordinary characteristics in medicine and nano-electronics. This study consists of two parts: (i) Fabrication and study of record small magnetic tunnel junctions (ii) Introduction of a novel method for detection of magnetoelectric nanoparticles (MENs) in the tissue.
A key challenge in further scaling of CMOS devices is being able to perform non-volatile logic with near zero power consumption. Sub-10-nm nanomagnetic spin transfer torque (STT) magnetic tunneling junctions (MTJs ...