Medicine and Health Sciences Commons^™

Serpin-Derived Novel Peptide For The Treatment Against Hiv-Induced Inflammation In The Central Nervous System, Yemmy Soler

FIU Electronic Theses and Dissertations

In the brain, HIV predominantly infects microglia/macrophages and astrocytes to a lesser extent. These cells form virus reservoirs with low levels of infection that are very hard to eradicate. Even though the use of cART increases survival rate in HIV patients, the virus persists as a chronic condition. cART is not able to effectively cross the BBB, control HIV replication, or attenuate inflammation in brain reservoirs. Therefore, the virus still causes neuronal dysfunction, pain-related pathology, and ultimately HAND. In this study, we decided to test the hypothesis that a serpin-derived small peptide, SP16, can serve as an anti-viral, anti-inflammatory, pro-survival, …

The Politics Of The Self: Psychedelic Assemblages, Psilocybin, And Subjectivity In The Anthropocene, Joshua Falcon

FIU Electronic Theses and Dissertations

This dissertation examines how psychedelic substances become drawn into particular sociohistorical and political arrangements, and how psychedelic experiences with psilocybin ‘magic mushrooms’ are used as tools of subjectivation. Guided by literatures in philosophy, critical theory, and the social sciences that focus on subjectivity, assemblage theory, and critical posthumanism, I argue that psychedelics are drawn into variegated assemblages, each of which conceptualizes the nature of psychedelics in highly specific ways that reflect implicit conceptions of the world and the self. In developing the concept of psychedelic assemblages, this research provides a window onto the politics of the self in the Anthropocene. …

Discovery Of First-In-Class Small Molecule Agonists Of The Rxfp2 Receptor As Therapeutic Candidates For Osteoporosis, Maria Esteban Lopez

FIU Electronic Theses and Dissertations

Osteoporosis is a chronic bone disease characterized by decreased bone mass and increased risk of developing fractures, predominantly observed in the elderly. The pathophysiological cause of the disease is a decrease in the activity of the bone-forming cells (osteoblasts) that alters bone remodeling in favor of bone resorption, leading to a decrease in bone mass. Recent studies identified the relaxin family peptide receptor 2 (RXFP2), the G protein-coupled receptor (GPCR) for insulin-like 3 peptide (INSL3), as an attractive target expressed in osteoblast cells to increase bone formation. The goal of this dissertation is to discover and characterize small molecule agonists …

Development Of A Microwave-Based Dna Extraction Method To Increase The Success Of Direct And Rapid Pcr Technique, Fabiana Taglia

FIU Electronic Theses and Dissertations

The goal of this project was to develop a fast, microwave-based extraction technique that could be employed for direct and rapid DNA analysis. The hypothesis was that the use of a microwave could increase the yield of DNA by opening the cell membrane, rendering the DNA available without the use of any other chemical treatment, and improving results from very low quantity samples.

At present rapid human DNA analysis is mainly restricted to genotyping saliva and sometimes blood samples. We hypothesized that microwave processing could expand the types of samples assessable to these procedures and increase sensitivity.

There were two …

Therapeutic Approaches To Alter Mineral Formation And Growth In Vascular Calcification, Amirala Bakhshiannik

FIU Electronic Theses and Dissertations

Cardiovascular diseases represent the global leading cause of morbidity and mortality. Cardiovascular calcification is the most significant predictor of cardiovascular events, but no therapeutic options exist to prevent or treat mineral formation in the vasculature. The presence of bone-like mineral increases cardiac work required to move blood through systemic circulation and can lead to mechanical stress in atherosclerotic plaques, promoting plaque rupture events that cause heart attacks. Clinical trials correlated bisphosphonates (BiPs), common anti-osteoporosis pharmaceuticals, with contradicting cardiovascular outcomes. Here, we demonstrated the importance of treatment timing in BiP-induced mineral disruption or promotion. We showed that BiPs can alter morphological …

Aptamer-Based Voltammetric Biosensing For The Detection Of Codeine And Fentanyl In Sweat And Saliva, Rosa Lashantez Cromartie

FIU Electronic Theses and Dissertations

Despite the many governmental and medicinal restrictions created to combat the opioid epidemic in the United States, opioid abuse and overdose rates continue to rise. The development of an aptamer-based voltammetric sensor and biosensor is described in this dissertation. The aim was to develop a low-cost, sensitive, and specific aptamer-based sensor for on-site, label-free determination of codeine and fentanyl in biological fluids. To do this, the surfaces of screen-printed carbon electrodes (SPCE) were modified with gold nanoparticles (AuNPs), followed by the addition of single-stranded DNA aptamers. These were covalently bound to the electrode surface. Operations of the sensors were collected …

Randomized Clinical Trial Of The Effect Of Oral Supplementation With N-Acetyl Cysteine And Glycine On Biomarkers Of Oxidative Stress And Inflammation In People Living With Hiv (Plwh) From The Mash Cohort, Alhanoof Al-Ohaly

FIU Electronic Theses and Dissertations

HIV infection has been associated with glutathione (GSH) depletion, oxidatively damaged DNA, and inflammation. People living with HIV (PLWH) have subnormal levels of GSH and elevated levels of inflammation biomarkers such as C-Reactive Protein (CRP). Failure of the antioxidant enzymatic system increases oxidatively damaged DNA. The objective of this double-blinded randomized clinical trial was to supplement PLWH with a combination of N-acetylcysteine, a powerful antioxidant, and glycine, a precursor of GSH or placebo for three months to decrease oxidative stress and inflammation.

The trial recruited 30 PLWH from the Miami Adult Studies on HIV (MASH) cohort at the FIU Research …

Towards Stable Electrochemical Sensing For Wearable Wound Monitoring, Sohini Roychoudhury

FIU Electronic Theses and Dissertations

Wearable biosensing has the tremendous advantage of providing point-of-care diagnosis and convenient therapy. In this research, methods to stabilize the electrochemical sensing response from detection of target biomolecules, Uric Acid (UA) and Xanthine, closely linked to wound healing, have been investigated. Different kinds of materials have been explored to address such detection from a wearable, healing platform. Electrochemical sensing modalities have been implemented in the detection of purine metabolites, UA and Xanthine, in the physiologically relevant ranges of the respective biomarkers. A correlation can be drawn between the concentrations of these bio-analytes and wound severity, thus offering probable quantitative insights …

Nucleoside Analogues For Positron Emission Tomography Imaging And To Study Radiation Mediated Generation Of Radicals From Azides, Maria E. De Cabrera

FIU Electronic Theses and Dissertations

Gemcitabine is a potent anticancer cytidine analogue used to treat solid tumors. Its efficacy is diminished by rapid deamination to a toxic uridine derivative by cytidine deaminase. To overcome this limitation and add radioactive nuclei (¹⁸F or ⁶⁸Ga) for PET imaging, I synthesized two 4-N­-alkylgemcitabine analogues i) bearing β-keto tosylate moiety for subsequent ¹⁸F-fluorination and ii) having SCN-Bn-NOTA chelator to complex ⁶⁸Ga. The first was synthesized by replacement of tosylamide in 4-N­-tosylgemcitabine with 1-amino-10-undecene, followed by elaboration of terminal alkene through dihydroxylation, regioselective tosylation and oxidation. Subsequent fluorination using KF in …

Topoisomerase And Tyrosyl-Dna-Phosphodiesterase Ratio As An Indicator For The Response Of Glioblastoma Cancer To Topoisomerase Targeting Anticancer Drugs, Wenjie Wang

FIU Electronic Theses and Dissertations

Glioblastoma (GBM) patients have an estimated survival of ~15 months, with the standard of care (surgery, radiation, and chemotherapy) that has only modestly enhanced patient survival. Identifying biomarkers representing vulnerabilities in GBM biology may allow for the selection of effective and safe chemotherapy options. Irinotecan (IRT), a genotoxic compound currently in clinical trials for GBM, targets topoisomerase I (TOP1) by forming an irreversible ternary DNA-TOP1 cleavage complex (TOP1cc) and leads to apoptosis. Tyrosyl-DNA phosphodiesterase 1 (TDP1) is a crucial repair enzyme that rescues TOP1cc and reduces the effectiveness of IRT. In the current study, we evaluate the value of the …

Multivariate Analysis For The Quantification Of Transdermal Volatile Organic Compounds In Humans By Proton Exchange Membrane Fuel Cell System, Ahmed Hasnain Jalal

FIU Electronic Theses and Dissertations

In this research, a proton exchange membrane fuel cell (PEMFC) sensor was investigated for specific detection of volatile organic compounds (VOCs) for point-of-care (POC) diagnosis of the physiological conditions of humans. A PEMFC is an electrochemical transducer that converts chemical energy into electrical energy. A Redox reaction takes place at its electrodes whereas the volatile biomolecules (e.g. ethanol) are oxidized at the anode and ambient oxygen is reduced at the cathode. The compounds which were the focus of this investigation were ethanol (C₂H₅OH) and isoflurane (C₃H₂ClF₅O), but theoretically, the sensor …

Mycobacterium Tuberculosis Inhibitors: Action And Resistance, Pamela K. Garcia-Moreno

FIU Electronic Theses and Dissertations

Tuberculosis, an infectious disease caused by Mycobacterium tuberculosis, has been a global health problem for years. The emergence of drug resistance in this organism generates the necessity of exploring novel targets and developing new drugs. Topoisomerases are enzymes found in all kingdoms of life responsible for overcoming the topological barriers encountered during essential cellular processes. The genomes of mycobacteria encode only one type IA topoisomerase (MtopI), which has been validated as a novel TB drug target. The goal of this study is to obtain new information on the mechanism and resistance of endogenous and synthetic inhibitors of MtopI.

Rv1495 is …

Azido- And Triazolyl-Modified Nucleoside/Tide Analogues: Chemistry, Fluorescent Properties, And Anticancer Activities, Zhiwei Wen

FIU Electronic Theses and Dissertations

Two classes of C5 azido-modified pyrimidine nucleosides were synthesized and explored as radiosensitizers. The 5-azidomethyl-2'-deoxyuridine (AmdU) was prepared from thymidine and converted to its cytosine counterpart (AmdC). The 5-(1-azidovinyl) modified 2'-deoxyuridine (AvdU) and 2'-deoxycytidine (AvdC) were prepared employing regioselective Ag-catalyzed hydroazidation of 5-ethynyl pyrimidine substrates with TMSN₃. AmdU and AmdC were converted to 5'-triphosphates AmdUTP and AmdCTP, and incorporated into DNA-fragments via polymerase-catalyzed reaction during DNA replication and base excision repair. Radiation-mediated prehydrated electrons formed in homogeneous aqueous glassy (7.5 M LiCl) systems in the absence of oxygen at 77 K led to site-specific formation of π-type aminyl …

Sab Concentration Determines The Chemotherapeutic Efficacy In Gynecological Cancer, Iru Paudel

FIU Electronic Theses and Dissertations

The American Cancer Society predicts there will be 110,070 new cases and 32,120 deaths due to gynecological malignancies in 2018. A major contributing factor to the high mortality associated with gynecological cancers is the recurrence of treatment-resistant tumors. Ovarian cancer (OC) remains the most lethal gynecological malignancy, yet the mechanisms responsible for regulating tumor resistance and vulnerability are largely unknown or undruggable. Therefore, the goal of this research is to identify mechanisms responsible for therapeutic resistance in gynecological cancers and discover innovative approaches to circumvent these molecular alterations. Our efforts began in OC where secondary analysis of gene expression data …

Epigenetic Instability Induced By Dna Base Lesion Via Dna Base Excision Repair, Zhongliang Jiang

FIU Electronic Theses and Dissertations

DNA damage can cause genome instability, which may lead to human cancer. The most common form of DNA damage is DNA base damage, which is efficiently repaired by DNA base excision repair (BER). Thus BER is the major DNA repair pathway that maintains the stability of the genome. On the other hand, BER mediates DNA demethylation that can occur on the promoter region of important tumor suppressor genes such as Breast Cancer 1 (BRCA1) gene that is also involved in prevention and development of cancer. In this study, employing cell-based and in vitro biochemical approaches along with bisulfite DNA sequencing, …

Enzyme Catalyzed And Ultrasound Assisted Transformation Of Selected Pollutants, Yi Tan

FIU Electronic Theses and Dissertations

The widespread use of synthetic drugs and as feed additives has resulted in the release of large amounts of biologically active chemicals into the environment. Exposure to environmentally relevant concentrations of chemicals can have severe effects on human health. Therefore, effective degradation of these synthetic, biologically active compounds is of paramount importance.

Diphenhydramine (DPH) has been selected as a target compound for ultrasound remediation. The results demonstrated that ultrasound-induced degradation has potential applications in managing aqueous media contaminated with DPH.

Atorvastatin and roxarsone have been selected as representative substrates for chloroperoxidase (CPO) catalyzed transformation of pollutants. These studies demonstrate atorvastatin …

Profiling Populations Using Neutral Markers, Major Histocompatibility Complex Genes And Volatile Organic Compounds As Modeled In Equus Caballus Linnaeus, Ketaki Deshpande

FIU Electronic Theses and Dissertations

Assessing the genetics of wild animal populations aims to understand selective pressures, and factors whether it be inbreeding or adaptation, that affect the genome. Although numerous techniques are available for assessing population structure, a major obstacle in studying wild populations is obtaining samples from the animals without having to capture them, which can lead to undue distress and injury. Therefore, biologists often use non-invasive sampling methods (i.e., collection of feces, hair) to extract host DNA. In this study, new DNA extraction protocols were developed that improved the quality and quantity of DNA obtained from fecal matter. Fecal samples aged up …

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) …

The Degradation Of Pharmaceutical Pollutants In Wastewater Catalyzed By Chloroperoxidase And The Construction Of Chloroperoxidase H105r Mutant, Qinghao He

FIU Electronic Theses and Dissertations

Trace amounts of pharmaceuticals have been detected in water, from nanograms per liter to micrograms per liter, and have a negatively effect in the aquatic environment and an increased potential risk of drug poisoning for human and animals. In order to address the problem, drug degradation catalyzed by chloroperoxidase (CPO) has been investigated. CPO is a heme-containing glycoprotein secreted by the fungus, Caldariomyces fumago, it catalyzes two major types of oxidations, two one-electron oxidations as catalyzed by most peroxidases and two-electron oxidations which are rare for conventional peroxidases.

Five common drugs from a variety of classes which were persistent in …

Conformational Dynamics And Stability Associated With Magnesium Or Calcium Binding To Dream In The Regulation Of Interactions Between Dream And Dna Or Presenilins, Khoa Ngoc Pham

FIU Electronic Theses and Dissertations

Downstream regulatory element antagonist modulator (DREAM) is involved in various interactions with targets both inside and outside of the nucleus. In the cytoplasm, DREAM interacts with the C-terminal fragments of presenilins to facilitate the production of β-amyloid plaques in Alzheimer’s disease. In the nucleus, Ca²⁺ free DREAM directly binds to specific downstream regulatory elements of prodynorphin/c-fos gene to repress the gene transcription in pain modulation. These interactions are regulated by Ca²⁺ and/or Mg²⁺ association at the EF-hands in DREAM. Therefore, understanding the conformational dynamics and stability associated with Ca²⁺ and/or Mg²⁺ binding to DREAM …

Extraction, Purification And Partial Characterization Of A Carotenoid Binding Protein (Cbp) From The Epidermis Of The Monarch Butterfly Larvae (Danaus Plexippus), Nan Fang

FIU Electronic Theses and Dissertations

This dissertation describes the purification and partial characterization of CBP from the epidermis of the monarch butterfly larvae (Danaus plexippus). A yellow protein-carotenoid complex was extracted from the yellow pigmented epidermal tissue from monarch butterfly larvae by homogenization. Additional steps in the purification process included differential precipitation with ammonium sulfate, cation and anion chromatography, and lastly size exclusion chromatography. Polyacrylamide gel electrophoresis demonstrates that a single protein was isolated (M-LBP) having a ~60 kDa molecular weight, the value has subsequently been confirmed by HR-tandem MS. Lutein is the sole carotenoid bound by M-LBP with a stoichiometry of the …

Design And Synthesis Of Novel Nucleoside Analogues: Oxidative And Reductive Approaches Toward Synthesis Of 2'-Fluoro Pyrimidine Nucleosides, Ramanjaneyulu Rayala

FIU Electronic Theses and Dissertations

Fluorinated nucleosides, especially the analogues with fluorine atom(s) in the ribose ring, have been known to exert potent biological activities. The first part of this dissertation was aimed at developing oxidative desulfurization-fluorination and reductive desulfonylation-fluorination methodologies toward the synthesis of 2'-mono and/or 2',2'-difluoro pyrimidine nucleosides from the corresponding 2'-arylthiopyrimidine precursors. Novel oxidative desulfurization-difluorination methodology was developed for the synthesis of α,α-difluorinted esters from the corresponding α-arylthio esters, wherein the arylthio group is present on a secondary internal carbon. For the reductive desulfonylation studies, cyclic voltammetry was utilized to measure the reduction potentials at which the sulfone moiety of substrates can …

Analysis Of Synthetic Cannabinoids By Direct Analysis In Real Time Quadrupole Time-Of-Flight Mass Spectrometry And Gas Chromatography Quadrupole Time-Of-Flight Mass Spectrometry, Tyler S. Torbet

FIU Electronic Theses and Dissertations

The aim of this study was to investigate the utility of direct analysis in real time quadrupole time-of-flight mass spectrometry and gas chromatography quadrupole time-of-flight mass spectrometry in the analysis of 162 different synthetic cannabinoids. Direct analysis in real time quadrupole time-of-flight mass spectrometry is shown to be a rapid and accurate analytical method for synthetic cannabinoids. Spectra can be generated with less than 1.5 ng of the drug in under a minute and be successfully searched against previously generated ESI-QTOF libraries in most cases (118/130 drugs tested) as well as can also be applied to the identification of synthetic …

Design And Synthesis Of S-Ribosylhomocysteine Analogues, Christiane Chbib

FIU Electronic Theses and Dissertations

Bacteria are known to release a large variety of small molecules known as autoinducers (AI) which effect quorum sensing (QS) initiation. The interruption of QS effects bacterial communication, growth and virulence.

Three novel classes of S-ribosylhomocysteine (SRH) analogues as potential inhibitors of S-ribosylhomocysteinase (LuxS enzyme) and AI-2 modulators of QS were developed. The synthesis of 2-deoxy-2-bromo-SRH analogues was attempted by coupling of the corresponding 2-bromo-2-deoxypentafuranosyl precursors with the homocysteinate anion. The displacement of the bromide from C2 rather than the expected substitution of the mesylate from C5 was observed. The synthesis of 4-C-alkyl/aryl-S-ribosylhomocysteine analogues involved the following steps: …

Design And Synthesis Of 4-N-Alkanoyl And 4-N-Alkyl Gemcitabine Analogues Suitable For Positron Emission Tomography, Jesse E. Pulido

FIU Electronic Theses and Dissertations

Gemcitabine is a highly potent chemotherapeutic nucleoside agent used in the treatment of several cancers and solid tumors. However, it is therapeutically limitated because of toxicity to normal cells and its rapid intracellular deamination by cytidine deaminase into the inactive uracil derivative. Modification at the 4-(N) position of gemcitabine's exocyclic amine to an -amide functionality is a well reported prodrug strategy which has been that confers a resistance to intracellular deamination while also altering pharmacokinetics of the parent drug. Coupling of gemcitabine to carboxylic acids with varying terminal moieties afforded the 4-N-alkanoylgemcitabines whereas reaction of 4-N …

Covalent Protein Adduction Of Nitrogen Mustards And Related Compounds, Vanessa R. Thompson

FIU Electronic Theses and Dissertations

Chemical warfare agents continue to pose a global threat despite the efforts of the international community to prohibit their use in warfare. For this reason, improvement in the detection of these compounds remains of forensic interest. Protein adducts formed by the covalent modification of an electrophilic xenobiotic and a nucleophilic amino acid may provide a biomarker of exposure that is stable and specific to compounds of interest (such as chemical warfare agents), and have the capability to extend the window of detection further than the parent compound or circulating metabolites. This research investigated the formation of protein adducts of the …

Aspects Of The Innate Immune System In The Caribbean Octocoral Swiftia Exserta, Lorenzo P. Menzel

FIU Electronic Theses and Dissertations

The immune systems of cnidaria are important to study for two reasons: to gain a better understanding of the evolution of immune responses, and to provide a basis to partially redress the precipitous world-wide die-offs of reef corals, some of which have been attributed to diseases and stress. Many immune responses share ancient evolutionary origins and are common across many taxa.

Using Swiftia exserta, an azooxanthellate ahermatypic local octocoral, as a proxy model organism to study aspects of innate immunity in corals and cnidaria allows us to address both of the reasons listed above while not using endangered species. …