Effects Of Waterborne Benzo[A]Pyrene Embryonic Exposure On Development, Behavior, Reproduction, And Mitochondrial Bioenergetics In Zebrafish, Megha Patel
Benzo[a]pyrene (BaP) is a polycyclic aromatic hydrocarbon (PAH) that is a known carcinogen leading to adverse effects in the development of both humans and animals. BaP is also continuously present in the environment leading to regular exposure via inhalation or ingestion. Because organisms’ early life stages can be more susceptible to contaminant exposure, our focus was on BaP’s adverse impacts on survival, length, weight, behavior, bioenergetic state, and fecundity following developmental exposures. To study BaP’s impacts, zebrafish (Danio rerio) were used as a model organism. BaP is a ligand for the aryl hydrocarbon receptor (AHR in ...
Digoxin Toxicity And Acute Renal Failure In A 75 Year-Old Female, 2022 Rowan University
Digoxin Toxicity And Acute Renal Failure In A 75 Year-Old Female, Daniel Zaayenga, Andrew Caravello, Nicholas Tomasello
Stratford Campus Research Day
Digoxin toxicity can present with varying manifestations. While pathognomonic symptoms such as xanthopsia (object appearing yellow) are a board favorite it is not a required finding and is in fact not seen with most patients. Rather digoxin toxicity presents with more non-specific symptoms such as GI distress (anorexia, N/V) neurological distress (lethargy, fatigue, delirium, confusion, disorientation, weakness. EKG findings are varied and include premature ventricular contractions, bradycardia, atrial tachyarrhythmias with AV block, ventricular bigeminy, junctional rhythms, various degrees of AV nodal blockade, ventricular tachycardia, and ventricular fibrillation. Although rarely seen, digoxin is one of the only causes of bidirectional ...
Synthesis Of Selenotryptophan For Protein Elucidation, 2022 Belmont University
Synthesis Of Selenotryptophan For Protein Elucidation, James P. Reiselman
Belmont University Research Symposium (BURS)
Through complex intermolecular and intramolecular forces, proteins conformationally change to form complex 3-d geometry that carries out biochemical processes and mapping their structures is becoming a field of interest in the biological community. Techniques for modeling protein’s structure typically follow the path of X-ray crystallography, which has an intrinsic phase problem that can make reading the electron density map they produce very difficult. This can be mitigated by appending a heavy-atom containing amino acid analogue into a crystal sample of the protein being studied. A selenium containing tryptophan analogue will be synthesized to be appended into proteins as a ...
Molecular Dynamics Simulations Of Self-Assemblies In Nature And Nanotechnology, 2021 The Graduate Center, City University of New York
Molecular Dynamics Simulations Of Self-Assemblies In Nature And Nanotechnology, Phu Khanh Tang
Dissertations, Theses, and Capstone Projects
Nature usually divides complex systems into smaller building blocks specializing in a few tasks since one entity cannot achieve everything. Therefore, self-assembly is a robust tool exploited by Nature to build hierarchical systems that accomplish unique functions. The cell membrane distinguishes itself as an example of Nature’s self-assembly, defining and protecting the cell. By mimicking Nature’s designs using synthetically designed self-assemblies, researchers with advanced nanotechnological comprehension can manipulate these synthetic self-assemblies to improve many aspects of modern medicine and materials science. Understanding the competing underlying molecular interactions in self-assembly is always of interest to the academic scientific community ...
Analysis Of Multigenerational Behavioral Effects Of Dietary Benzo[A]Pyrene Exposure In Adult Zebrafish, 2021 University of Mississippi
Analysis Of Multigenerational Behavioral Effects Of Dietary Benzo[A]Pyrene Exposure In Adult Zebrafish, Mary Beth Gillespie
Benzo[a]pyrene (BaP) is a polycyclic aromatic hydrocarbon that is linked to negative reproductive and developmental effects in humans and animals. Because BaP is carcinogenic, and its continued presence in the environment allows it to be inhaled and ingested, better understanding of the effects of BaP is needed. To determine the behavioral effects of BaP exposure, zebrafish were used as a model. Wild-type zebrafish (5D) underwent two separate 21-day dietary exposures to 2.5 and 25 μg BaP/g fish to compare how BaP exposure affects locomotor activity. Following the dietary exposure, fish were mated to obtain and raise ...
Applied Molecular Dynamics: From Targeting Viral Helicases, To Understanding The Interactions Of Cucurbituril Complexes In Ionic Solutions, Bryan Raubenolt
University of New Orleans Theses and Dissertations
Molecular Dynamics simulations are a highly useful tool in helping understand the fundamental interactions present in a variety of chemical systems. The work discussed here illustrates it’s use in determining the conformational dynamics of the Zika and SARS-Cov-2 helicase in a physiological environment, largely in an effort to discover inhibitors capable of rendering the protein inert. Additionally, we show how it can be used to understand paradoxical trends in the anion-induced precipitation of Cucurbituril cavitands.
Viral helicases are motor proteins tasked with unwinding the viral dsRNA, a crucial step in preparing the strand to be translatable by host cells ...
Fluorometric Characterization Of A Methylene Blue Derivative Sensitive To Reactive Oxygen Species (Ros), 2020 University of Mississippi
Fluorometric Characterization Of A Methylene Blue Derivative Sensitive To Reactive Oxygen Species (Ros), Matthew Weeks
Methylene blue (MB) has many uses within both microbiology and pharmacology. MB can treat disorders such as methemoglobinemia, malaria, Alzheimer’s disease, and certain forms of cancer. MB is also useful for molecular imaging due to its off-on fluorescent capabilities. MB derivatives with a urea bond at the 10-N position have been cleavable by triggers such as light. However, I was interested in sensitivity to reactive oxygen species (ROS). In this study, I wanted to determine if the MB derivative MB-EA exhibited sensitivity to ROS. MB-EA was exposed to varying concentrations of hydrogen peroxide and MB release was measured. I ...
Impact Of Estradiol Variability And Progesterone On Mood In Perimenopausal Women With Depressive Symptoms, 2019 Harvard Medical School
Impact Of Estradiol Variability And Progesterone On Mood In Perimenopausal Women With Depressive Symptoms, Hadine Joffe, Anouk De Wit, Jamie Coborn, Sybil L. Crawford, Marlene Freeman, Aleta Wiley, Geena Athappilly, Semmie Kim, Kathryn A. Sullivan, Lee S. Cohen, Janet E. Hall
Tan Chingfen Graduate School of Nursing Publications
OBJECTIVE: To determine whether estradiol variability, ovulatory levels of progesterone, and VMS burden are independently associated with perimenopausal depressive symptomatology.
DESIGN AND INTERVENTION: Depressive symptoms, serum levels of estradiol and progesterone, and VMS frequency were assessed weekly in an 8-week observational study. Association of mood with estradiol variability, ovulatory levels of progesterone, and VMS frequency were estimated using generalized estimating equation models.
SETTING: Academic medical center.
PATIENTS: Fifty unmedicated perimenopausal women with mild-to-moderate depressive symptoms (mean Montgomery-Asberg Depression Rating Scale [MADRS] score 15.5 +/- 5.3).
RESULTS: During the study, 90.0% of participants had varying estradiol levels, 51.1 ...
Letter: When Less Is More: Dexamethasone Dosing For Brain Tumors, 2019 Baptist Health Medical Group; Miami Cancer Institute
Letter: When Less Is More: Dexamethasone Dosing For Brain Tumors, Minesh Mehta
No abstract provided.
Catalyzed And Uncatalyzed Modifications Of Nucleosides, Synthesis Of Hippadine, And Deuterated 1,2,3-Triazoles, 2018 The Graduate Center, City University of New York
Catalyzed And Uncatalyzed Modifications Of Nucleosides, Synthesis Of Hippadine, And Deuterated 1,2,3-Triazoles, Hari K. Akula
Dissertations, Theses, and Capstone Projects
The C4 amide carbonyl of O-t-butyldimethylsilyl-protected thymidine, 2’-deoxyuridine, and 3’-azidothymidine (AZT) was activated by reaction with (benzotriazol-1-yloxy)tris(dimethylamino) phosphonium hexafluorophosphate (BOP) and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in THF as solvent. This led to the formation of corresponding O4-(benzotriazol-1-yl) derivatives, which are reactive intermediates. Substitution at the C4 position was then carried out by reactions with alkyl and aryl amines, and thiols. Typically, reactions were conducted as a two-step, one-pot transformation, and also as a one-step conversion. After examining the reactions, the formation of 1-(4-pyrimidinyl)-1H-benzotriazole-3-oxide derivatives from the ...
C. Elegans Multidrug Resistance Protein 5 (Mrp-5) Transports Vitamin B12 From The Intestine To The Gonad To Support Embryonic Development [Preprint], 2018 University of Massachusetts Medical School
C. Elegans Multidrug Resistance Protein 5 (Mrp-5) Transports Vitamin B12 From The Intestine To The Gonad To Support Embryonic Development [Preprint], Huimin Na, Olga Ponomarova, Gabrielle E. Giese, Albertha J. M. Walhout
UMass Chan Medical School Faculty Publications
Vitamin B12 functions as a cofactor for methionine synthase to produce the anabolic methyl donor S-adenosylmethionine (SAM) and for methylmalonyl-CoA mutase to catabolize the short chain fatty acid propionate. In the nematode Caenorhabditis elegans, maternally supplied vitamin B12 is required for the development of her offspring. However, the mechanism for exporting vitamin B12 from the mother to her offspring is not yet known. Here, we use RNAi of more than 200 transporters with a vitamin B12-sensor transgene to identify the ABC transporter MRP-5 as a candidate vitamin B12 exporter. We show that injection of vitamin B12 into the gonad of ...
Unsuspected Clenbuterol Toxicity In A Patient Using Intramuscular Testosterone, 2017 University of Massachusetts Medical School
Unsuspected Clenbuterol Toxicity In A Patient Using Intramuscular Testosterone, Matthew K. Griswold, Eike Blohm, Roderick Cross, Edward W. Boyer, Jennifer L. Carey
Emergency Medicine Publications
Clenbuterol is a beta-agonist that has been abused by fitness-oriented individuals for muscle growth and weight loss. We report a case of a 46-year-old man who presented tachycardic, hypokalemic, and hyperglycemic after injecting testosterone obtained from Brazil. He developed refractory hypotension and was started on an esmolol infusion for suspected beta-agonist toxicity. Laboratory analysis showed a detectable clenbuterol serum concentration. Analysis of an unopened ampule contained boldenone undecylenate, clenbuterol, and vitamin E. This case illustrates a novel exposure that caused beta-agonist toxicity and was treated successfully with rapid-onset beta blocker.
Diversity Oriented Synthesis, Characterization And Anti-Cancer Activity Of Killer Peptide Nucleolipid Bioconjugates, Niki K. Rana
Seton Hall University Dissertations and Theses (ETDs)
The killer peptide sequence D-(KLAKLAK)2 has been originally designed and developed as an antibacterial agent. Despite having excellent cytotoxicity towards bacteria, this sequence maintains low cell cytotoxity in malignant mammalian cell types such as cancer. The chemical basis for its selectivity has been attributed to its poly(cationic) amphiphilic nature, which facilitates cell permeability across the negatively charged bacterial membrane, but with limited permeability across the zwitterionic membrane of mammalian cells. The positively charged D-(KLAKLAK)2 sequence has been found to accumulate on the surface of the mitochondria causing dissipation of the negatively charged mitochondrial membrane potential ...
Structure Activity Relationship Studies Of Novel Diarylpentanoid Analogs Targeting The Androgen Receptor In Prostate Cancer Cells, Haili Coffin, Marco Bisoffi
Student Scholar Symposium 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 ...
Chemoselective And Stereoselective Exploration Of The Chemical Reactivity Space Of Castagnoli-Cushman-Derived Allylic Lactamoyl Esters: Application To The Synthesis Of Aza-Polycyclic Architectures, 2017 Central Washington University
Chemoselective And Stereoselective Exploration Of The Chemical Reactivity Space Of Castagnoli-Cushman-Derived Allylic Lactamoyl Esters: Application To The Synthesis Of Aza-Polycyclic Architectures, Brandon Joseph Mansker
All Master's Theses
The synthesis and evaluation of structure-activity relationships of saturated nitrogen heterocycles is the focal point of various pharmaceutical companies thanks to the high biological activity of previously isolated azacycles. Here, we describe an operationally simple and highly efficient approach to macrocyclic lactams bearing vicinal stereocenters and a challenging cycloalkyne motif. The outcomes are achieved through a novel [4 + 2] cycloaddition reaction between an N-iodoarylated-1,3-azadiene and cyclic anhydrides, followed by interception of the cycloadducts in cross-coupling manifolds (e.g., Sonogashira coupling) and concomitant lithiation-cyclization of the tethered alkyne. An unprecedented example of a hydroamino alkylation that is transition metal-free ...
A Diversity-Oriented Synthesis Approach To Functionalized Azaheterocycles Using Cyclic Alpha-Halo Eneformamides, 2017 Central Washington University
A Diversity-Oriented Synthesis Approach To Functionalized Azaheterocycles Using Cyclic Alpha-Halo Eneformamides, Spencer A. Langevin
All Master's Theses
Functionalized piperidines, azepanes, azamacrocycles, morpholines, and thiomorpholines are common structural motifs found in a wide range of pharmaceuticals such as carmegliptine, levofloxacin, thioridazine, claviciptic acid, and azithomycin. As a result, there is a strong desire to construct highly functionalized nitrogen-bearing ring scaffolds in order to construct a wide range of drug possibilities. There are several non-modular and step-uneconomical synthetic methods used in the construction of these aforementioned motifs such as ring closing metathesis, ring expansions, and intramolecular reductive amination. In this research, we present a step-economical, cost-effective, scalable, and diversity-oriented synthesis approach to highly functionalized N-heterocycles through the intermediacy of ...
Emerging Evidence For Beneficial Macrophage Functions In Atherosclerosis And Obesity-Induced Insulin Resistance, 2016 University of Massachusetts Medical School
Emerging Evidence For Beneficial Macrophage Functions In Atherosclerosis And Obesity-Induced Insulin Resistance, Timothy P. Fitzgibbons, Michael P. Czech
UMass Chan Medical School Faculty Publications
The discovery that obesity promotes macrophage accumulation in visceral fat led to the emergence of a new field of inquiry termed "immunometabolism". This broad field of study was founded on the premise that inflammation and the corresponding increase in macrophage number and activity was a pathologic feature of metabolic diseases. There is abundant data in both animal and human studies that supports this assertation. Established adverse effects of inflammation in visceral fat include decreased glucose and fatty acid uptake, inhibition of insulin signaling, and ectopic triglyceride accumulation. Likewise, in the atherosclerotic plaque, macrophage accumulation and activation results in plaque expansion ...
Synthesis Of Β-Triphosphotriester Pronucleotides, 2015 Tennessee State University
Synthesis Of Β-Triphosphotriester Pronucleotides, Yousef A. Beni, Chandravanu Dash, Keykavous Parang
Pharmacy Faculty Articles and Research
Dinucleoside phosphorochloridite were synthesized from phosphorus trichloride and three nucleoside analogues, 3-fluoro-2,3-dideoxythymidine (FLT), 2',3'-dideoxy-5-fluoro-3'- thiacytidine (FTC), and 2',3'-dideoxy-3'-thiacytidine (3TC), in a multistep synthesis. Polymerbound N-Boc p-acetoxybenzyl 5¢-O-2¢-deoxythymidine was reacted with dinucleoside phosphorochloridite in the presence of 2,6-lutidine, followed by the reaction with dodecyl alcohol and 5-(ethylthio)-1H-tetrazole, oxidation with tert-butyl hydroperoxide, and acidic cleavage, respectively, to afford the b-triphosphotriester derivatives containing three different nucleosides.
Target-Directed Biosynthetic Evolution: Redirecting Plant Evolution To Genomically Optimize A Plant’S Pharmacological Profile, Dustin Paul Brown
Theses and Dissertations--Neuroscience
The dissertation describes a novel method for plant drug discovery based on mutation and selection of plant cells. Despite the industry focus on chemical synthesis, plants remain a source of potent and complex bioactive metabolites. Many of these have evolved as defensive compounds targeted on key proteins in the CNS of herbivorous insects, for example the insect dopamine transporter (DAT). Because of homology with the human DAT protein some of these metabolites have high abuse potential, but others may be valuable in treating drug dependence. This dissertation redirects the evolution of a native Lobelia species toward metabolites with greater activity ...
Testosterone Treatment Does Not Facilitate Prefrontal Cortex Mediated Cognition In Male Marmosets (Callithrix Jacchus), 2014 University of Massachusetts Amherst
Testosterone Treatment Does Not Facilitate Prefrontal Cortex Mediated Cognition In Male Marmosets (Callithrix Jacchus), Matthew Laclair, Jeemin Chang, Agnes Lacreuse
UMass Center for Clinical and Translational Science Research Symposium
Aging in men is associated with decreases in serum testosterone (T) and a decline in cognitive abilities. We sought to clarify the relationship between T, aging and cognition using the common marmoset (callithrix jacchus), which has been shown to be a useful model of human aging. Ten castrated male marmosets (ages 3-8) were given weekly injections of either T cypionate dissolved in cottonseed oil (T, n = 5) or cottonseed oil alone (controls, n = 5). Cognitive function was assessed with two tasks, the object reversals (OR) and the delayed response (DR). Marmoset behavior was recorded twice daily using a modified frequency ...