Life Sciences Commons^™

Theranostics For Antiretroviral Biodistribution And Pharmacokinetics, Brendan M. Ottemann

Theses & Dissertations

RATIONALE: Our laboratories birthed the field of human immunodeficiency virus (HIV) theranostics. The new field allows simultaneous detection (diagnostics) and treatment (therapeutic) for the identification, treatment and inevitable elimination of virus in cell and tissue compartments. By employing theranostics, antiretroviral drugs (ARVs) can be tracked in lymph nodes, gut, spleen and liver. Cellular viral reservoirs including CD4+ T cell populations and mononuclear phagocytes (MP; monocytes, macrophages, microglia and dendritic cells) along with subcellular endosomal structures can now be targeted for drug delivery bringing therapeutics to areas where virus replicates. The overarching idea rests in improving precision targeted ARV delivery. …

Feeding The Future Meat Doesn’T Come Cheap, Lukas C. Southard

Capstones

Cultured – or as it is referred to by companies innovating the technology clean – meat is expected to be the next innovation to change the way the world gets its animal protein. Meat from animal cells grown in a lab seems like science fiction but it is around the corner from hitting your supermarket shelves. The technology has been developed but how these companies intend on scaling up their production to meet retail demands remains a mystery. So far companies have relied on seed and early stage investment from venture capital companies and private sources to fund research. Predictions …

Inhibition Of Serine, Glycine, One-Carbon Metabolism Reduces Proinflammatory Response, Ashlynn Mccall

Honor’s College Freeman Research Journal

Acute lung injury affects around 200,000 critically ill patients annually, with a mortality rate near 33%. With a lack of targeted therapies, it is vital to discover and understand the fundamental cellular processes that drive macrophage inflammation. In the field of macrophage immunometabolism, it is accepted that macrophages upregulating glycolysis indicates a role in proinflammatory processes, however, there is a lack of knowledge surrounding the intermediate pathways in glycolysis. This study examined the effects of serine, glycine, one-carbon metabolism inhibition on LPS-induced inflammation in bone marrow-derived macrophages. We show that the enzymatic expression of PHGDH and PSATl is unaffected when …

The Antimicrobial Activity And Cellular Targets Of Plant Derived Aldehydes And Degradable Pro-Antimicrobial Networks In Pseudomonas Aeruginosa, Yetunde Adewunmi

Dissertations

Essential oils (EOs) are plant-derived products that have been long exploited for their antimicrobial activities in medicine, agriculture, and food preservation. EOs represent a promising alternative to conventional antibiotics due to the broad-range antimicrobial activity, low toxicity to human commensal bacteria, and the capacity to kill microorganisms without promoting resistance. Despite the progress in the understanding of the biological activity of EOs, many aspects of their mode of action remain inconclusive. The overarching aim of this work was to address these gaps by studying molecular interactions between antimicrobial plant aldehydes and the opportunistic human pathogen Pseudomonas aeruginosa. We initiated …

Molecular Survey Of Helminths Infecting Ground Dwelling Birds In The Grouse Subfamily Tetraoninae, Briana M. Sesmundo

Honors College Theses

Alaskan grouse and ptarmigan (Galliformes) are important avian game species in Alaska. Interestingly, gallids harbor a fairly diverse helminth fauna, particularly cestodes, which may make birds with high parasite loads more susceptible to predation. Unfortunately, there is limited information available on the helminth fauna of Alaskan gallids, and no molecular surveys. The present study aims to develop baseline data on diversity of intestinal and subcutaneous (filariid) helminth infections in galliforms using morphological and molecular (DNA) approaches. These data can then be used to better understand changes in helminth community structure given current environmental volatility. The intestines, cloaca, liver and kidneys …

In Vitro Investigation Of The Effect Of Camel Milkproteins And Its Fractions On Insulin Receptor Function, Arshida Ashraf

Biology Theses

Camel milk (CM) has been reported to have anti-diabetic properties in many in vitro and in vivo studies but the molecular basis of such beneficial properties are still elusive. Recently, camel milk whey proteins (CWPs) have been shown to positively affect the activity of the human insulin receptor (hIR) in cell lines. In this study, we profiled crude CWPs and their hydrolysates as well as camel milk lactoferrin (CMLF) for their pharmacological and functional effects on hIR activity and its downstream signaling in both human embryonic kidney (HEK293) and hepatocarcinoma (HepG2) cell lines. For this, bioluminescence resonance energy transfer (BRET) …

Forensic Evaluation Of 6-Dye Chemistry Kit Composed Of 23 Loi With Casework Samples, Naeema Saleh Al Janaahi

Biology Theses

Short Tandem Repeats (STRs) are short nucleotide sequence repeats consisting of 2-8 base pairs (bp), representing approximately 3% of human DNA. Markers of STRs have been widely used as genetic markers in forensic DNA analysis and have proven to be an extremely discriminating method for human identification in forensics. The main objective of this research was to evaluate a six-dye STR multiplex assay (Virifiler™ Plus) composed of 23 autosomal STR loci, one insertion/deletion polymorphic marker on the Y chromosome, Amelogenin and two internal quality control markers (IQCS and IQCL) using biological stains found in different crime scenes. The study investigated …

The Association Of Dna And Histone Methyltransferase Genes With Different Methylation Levels In Fragile X Syndrome Individuals, Sara Humaid Sembaij

Theses

Fragile X Mental Retardation 1 (FMR1) gene produces an FMR protein (FMRP) which is known to regulate the translation process in various organs. It has a significant role in neurons function, maturation, and synaptic plasticity. FMR1 gene encompasses 5 - 30 CGG repeats and the greater number of repeats has the potential to expand during gametogenesis. The expansion depending on the number of CGG repeat undergoes hyper-methylation and is considered as a dynamic mutation in which the expansion increases through generation. Methylation of expanded CGG repeats results in inhibiting the transcription and silencing the gene. There are two types of …

The Democratization And Development Of Cell-Free Protein Synthesis, Max Z. Levine

Master's Theses

Cell-free protein synthesis (CFPS) using crude lysates has developed into a robust platform technology over the last 60 years to express numerous types of recombinant proteins. The open-nature, elimination of reliance on cell viability, and focus of all energy towards production of the protein of interest represent substantial advantages of CFPS over in vivo protein expression methods. CFPS has provided new opportunities across a series of research fields that include metabolic engineering, therapeutic and vaccine development, education, biosensors, and many more. In recent years, optimizations of CFPS have even allowed the platform to reach the industrial level of protein production. …

The Catalytic Urease Subunit Urec Is Critical For Bifidobacterium Longum Urea Utilization, Yang Lyu

Doctoral Dissertations

In the first study, we investigated the utilization of a human milk nitrogen source, urea, by Bifidobacterium. Urea accounts for ~15% in human milk, which is an abundant non-protein nitrogen (NPN). Some bifidobacteria are found to harbor urease gene clusters that potentially enable their hydrolysis of the human milk urea. However, the underlying mechanisms are still unclear. To incisively link the urease gene cluster with bifidobacterial urea utilization, chemical mutagenesis (i.e. ethyl methanesulfonate) was performed on the urease-positive Bifidobacterium longum subsp. suis UMA399. Mutants were selected on differential media and genetic lesions were identified using whole genome sequencing. …

Engineering Of An Antibody-Conjugated Nanogel Platform For Targeted Drug Delivery To T Lymphocytes, Mine Canakci

Doctoral Dissertations

In an ideal chemotherapy, cytotoxic drugs travel through the bloodstream, reach cells all over the body and preferentially kill abnormal cells. Yet, the hydrophilic or lipophilic property of the small-molecule drugs affects their ability to reach cells from the bloodstream. So, only a small portion of the drug reaches to the diseased tissue. A selective cell killing approach for cancer therapy gained momentum after the realization that cancer cells carry unique set of molecular markers on their cell surface. The development of antibody drug conjugates (ADC) revolutionized the targeted approach for drug delivery. ADCs are composed of cytotoxic agents covalently …

Investigating The Role Of Lbh During Early Embryonic Development In Xenopus Laevis, Emma Weir

Masters Theses

LBH is a highly conserved protein whose role during vertebrate development is relatively under-studied. In collaboration with the Albertson lab, our lab has previously shown that it is necessary for cranial neural crest cell migration in the zebrafish and in Xenopus laevis. The molecular mechanisms through which it acts are not well understood.

In Xenopus, LBH is a maternally deposited protein. As such, studying its role in early development has not been feasible through the morpholino-mediated knockdown techniques that prevent translation of target genes. Recently, a technique for degrading endogenous proteins was developed, called Trim-Away. This was developed in mammalian …

Bioremediation Of Refinery Desalter Effluent Using Debaryomyces Hansenii And Parachlorella Kessleri, Leila Azimian

Electronic Thesis and Dissertation Repository

Crude oil desalting operations produce an effluent stream which is challenging to treat due to its salt, heavy metal and hydrocarbon content. Consequently, desalter effluent (DE) is usually diluted into other effluent streams and sent to conventional wastewater treatment plants which may lead to upsets the plant operation.

In this study, a novel microbial approach was applied which investigated DE treatment using halotolerant yeast Debaryomyces hansenii (LAF-3 10 U) or the environmentally robust micro-algae Parachlorella kessleri strain CPCC 266. The effect of these two different approaches on both synthetic and actual DE was investigated in both batch and/or continuous mode. …

Eugenics In The 21st Century, Jessica Linn Chin

Dissertations, Theses, and Capstone Projects

Eugenics is the science of enhancing the human population through the management of breeding and hereditary traits. This thesis explores the history of eugenics and shows how eugenic practices continue in the 21^st century with advancements in technology and positive eugenic goals that can result in adverse effects on the human body and society. When Sir Francis Galton coined the term eugenics in 1883, he intended to improve British society with the use of positive eugenics. Galton used positive eugenics to encourage people with good mental and physical qualities to produce more children. He avoided negative eugenics, which involved …

Renal Specific Rnai Delivery By Fibrillar Nanoparticle Excipients, Sam Wong

Dissertations, Theses, and Capstone Projects

RNA interference (RNAi) is a powerful tool to manipulate the phenotype of an organism by silencing the expression of specific genes and is viewed as a highly promising platform for treating undruggable targets and disorders where small molecule drugs and antibodies would fail. However, development of RNAi based therapies has faced major barriers including cellular and tissue-specific uptake of the Small Interfering RNA (siRNA). Utilizing different nanoparticles as RNAi excipients, cellular uptake and gene silencing potency can be greatly improved. The research in Dr. McDevitt groups has fibrillar carbon nanotubes (CNT) as carriers for siRNA for gene silencing in vitro …

Developing A Dissociative Nanocontainer For Peptide Drug Delivery, Michael Patrick Kelly

Dissertations, Theses, and Capstone Projects

The potency and specificity of bioactive peptides have propelled these agents to the forefront of pharmacological research. However, delivery of peptides to their molecular target in cells is a major obstacle to their widespread application. A Trojan Horse strategy of packaging a bioactive peptide within a modified protein cage to protect it during transport, and releasing it at the target site, is a promising delivery method. Recent work has demonstrated that the viral capsid of the P22 bacteriophage can be loaded with an arbitrary, genetically-encoded peptide, and externally decorated with a cell-penetrating peptide, such as HIV-Tat, to translocate across in …

Ipsc Based Gene Correction And Disease Model Of A New Class Of Lgmd Due To Poglut1 Mutation, Jose Ortiz-Vitali

Dissertations & Theses (Open Access)

Recently, a novel class of muscular dystrophy has been discovered in a family due to autosomal recessive missense mutation in POGLUT1. Mutation of this enzyme leads to decreased O-glucosyltransferase activity and impaired Notch signaling, the pathways important for skeletal muscle stem cell (satellite cells) quiescence and activation. We hypothesize that reduced POGLUT1 activity and impaired Notch signaling is causative of this limb girdle muscular dystrophy through dysfunction of muscle stem cells and myogenic progenitors.

To test this, we have used iPSCs for disease modeling and rescue experiments. Using a CRISPR based gene targeting method, we aimed to correct the point …

Sequence Analysis Of The Ren1 Genomic Region From The Grapevine ‘Kishmish Vatkana’, Dani Joseph

MSU Graduate Theses

The REN1 region of the grapevine ‘Kishmish Vatkana’ was mapped as the locus that confers resistance to the economically important disease, grape powdery mildew. The purpose of this work was to extend the nucleotide sequence information of this region. By sequencing a heretofore unknown bacterial artificial chromosome clone, the sequence information of this region was extended by 46,890 nucleotides. Sequencing was performed using the third-generation sequencing method, named Oxford Nanopore Technology (ONT). In order to improve the accuracy of the sequence data, a modified ONT library preparation method was developed. ONT sequencing of a library prepared with the modified protocol …

Development Of Novel Zika And Anthrax Viral Nanoparticle Vaccines, Elizabeth Henderson

KGI Theses and Dissertations

Vaccines protect against numerous infectious diseases and prevent millions of deaths annually, but there are still many infectious diseases for which no licensed vaccine exists. Developing a new vaccine requires balancing safety and efficacy, and viral nanoparticle (VNP) vaccines possess both of these characteristics. The work herein demonstrates how tobacco mosaic virus (TMV) nanoparticles can serve as a platform to create candidate vaccines for Zika virus (ZIKV) and anthrax. In the first study, a ZIKV-specific epitope was genetically fused to TMV to create a safe and inexpensive vaccine that proved highly immunogenic in mice and led to the discovery of …

Synthesis Of New Aliphatic Pseudo-Branched Polyester Co-Polymers For Biomedical Applications, Zachary Shaw

Electronic Theses & Dissertations

In this study, a hyperbranched polyester co-polymer was designed using a proprietary monomer and diethylene glycol or triethylene glycol as monomers. The synthesis was carried out using standard melt polymerization technique and catalyzed by p-Tolulenesulfonic acid. The progress of the reaction was monitored with respect to time and negative pressure, with samples being subjected to standard characterization protocols. The resulting polymers were purified using the solvent precipitation method and characterized using various chromatographic and spectroscopic methods including GPC, MALDI-TOF, and NMR. We have observed polymers with a molecular weight of 29,643 kDa and 33,996 kDa, which is ideal to be …

Maximizing And Modeling Malonyl-Coa Production In Escherichia Coli, Tatiana Thompson Silveira Mello

LSU Master's Theses

In E. coli, fatty acid synthesis is catalyzed by the enzyme acetyl-CoA carboxylase (ACC), which converts acetyl-CoA into malonyl-CoA. Malonyl-CoA is a major building block for numerous of bioproducts. Multiple parameters regulate the homeostatic cellular concentration of malonyl-CoA, keeping it at a very low level. Understanding how these parameters affect the bacterial production of malonyl-CoA is fundamental to maximizing it and its bioproducts. To this end, competing pathways consuming malonyl-CoA can be eliminated, and optimal nutritional and environmental conditions can be provided to the fermentation broth. Most previous studies utilized genetic modifications, expensive consumables, and high-cost quantification methods, making …

Compositional Optimization Of Amyloid-Graphene Oxide Nanohybrids For Biomaterials, Claire L. Drewery

Materials Engineering

Amyloid nanofibrils are natural materials capable of self-assembling into precise structures with tunable functionalities, while exhibiting excellent mechanical properties. In combination with highly conductive graphene oxide (GO), the 1-D amyloid nanofibrils and 2-D nanosheets of GO can produce a robust and bio-functional nanohybrid, hypothesized to exhibit multi-domain functional properties useful for enzyme sensing, water purification, drug delivery, and tissue scaffolding applications. Here, we examine the properties of an amyloid-graphene oxide nanohybrid film made with amyloids derived from hen egg white lysozymes in an attempt to explore the diverse toolbox of amyloid derivatives and establish ideal fabrication methods and formulations of …

Developing A Low Cost Biological Additive Manufacturing System For Fabricating Gel Embedded Cellular Constructs., Justin Stewart Minck

Electronic Theses, Projects, and Dissertations

Organ transplantation has made great progress since the first successful kidney transplant in 1953 and now more than one million tissue transplants are performed in the United States every year (www.organdonor.gov/statistics-stories, 2015). However, the hope and success of organ transplants are often overshadowed by their reputation as being notoriously difficult to procure because of donor-recipient matching and availability. In addition, those that are fortunate enough to receive a transplant are burdened with a lifetime of immunosuppressants. The field of regenerative medicine is currently making exceptional progress toward making it possible for a patient to be their own donor. Cells from …

Genetic Variation Of Human Leukocyte Antigen (Hla) Alleles Among Rheumatiod Arthritis Patients In Fujairah, Amna Abdulla Harib Al-Dhmanie

Biology Theses

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation that affects the joints. It occurs when the immune system attacks the body's own tissues and organs. The precise cause of RA is not fully understood but evidence suggests that genes, hormones and environmental factors could be involved. It has been established that human leukocyte antigen (HLA) loci is a strong risk factor of RA. Specifically, the shared epitope (SE) region of HLA-DRB1 and variations at position 11 and 13 of HLA-DRB1 and position 77 of HLA-A have shown strong association with RA. The hypothesis of this study was …

Estrategias De Manejo Para Mejorar La Producción Piscícola En Un Sistema De Jaulas Flotantes Con Tilapia Roja Oreochromis Sp, En Montería, Córdoba, Carlos Alberto Sierra, Jaime Jenaro Maroso

Zootecnia

El presente estudio de caso es realizado en la Granja Las Acacias, en el municipio de Montería, capital del departamento de Córdoba; donde se encuentra una producción intensiva de tilapia roja (Oreochromis sp) en sistema de jaulas flotantes. Se determinaron los indicadores productivos en promedio para las 15 jaulas en 182 días, los cuales fueron: biomasa (879 kg/m3), conversión alimenticia (CA=2,41) y ganancia de peso diaria (0,92 g); además de parámetros fisicoquímicos del agua mediante equipos de la marca HACH, tales como oxígeno disuelto (OD=3,92mg/l), temperatura mínima (24C), temperatura máxima (32C ) y pH (7.5). Basados en el estado del …

Study Of Paper Microbial Fuel Cells For Use In On-Site Wastewater Testing, William A. Tolmasoff

Master's Theses

This study demonstrated a technique for fabricating simple, low-cost Paper Microbial fuel cells (PMFC’s) in the model of a previous study to, for the first time, produce voltage from wastewater effluent. The PMFC’s were created by stacking and gluing the main components of an MFC together: reservoir layer; anode; cation exchange membrane (CEM); air cathode. A wax printer was used to create the hydrophobic borders of the PMFC’s on filter paper, and graphite paint was applied to the paper to create the anode. The CEM’s considered were filter paper, wax, and Nafion, with Nafion being the most efficient. Finally, the …

Cultivating Knowledge: Agrarian Science And Ecological Engagements In Southern Ontario Agriculture, Kelly Linton

Electronic Thesis and Dissertation Repository

Agriculture and climate change are interconnected processes, with agriculture implicated in rising green house gas emissions, deforestation, soil and water pollution, and reductions in biodiversity. Conversely, changes within ecology (including a warming climate), alter growing conditions for farmers. Farmers face changes in both temperature and precipitation, as well as an increase in adverse weather events that significantly threaten productivity and livelihoods.

Based on 40 unstructured interviews as well as informal conversations conducted among farmers in southern Ontario, Canada between the spring of 2014 and the winter of 2017, this dissertation seeks to contribute to a growing body of work that …

Microrna Profiling And Engineering Of Cho Cell Lines Stably Expressing Difficult-To-Express Lysosomal Protein, Ifeanyi Amadi

KGI Theses and Dissertations

Difficult-to-express (DTE) recombinant proteins like multi-specific proteins, DTE monoclonal antibodies and lysosomal enzymes, have seen difficulties in manufacturability using Chinese hamster ovary (CHO) cells and other mammalian cells as production platforms. CHO cells are preferably used for protein production because of their innate ability to secrete human-like recombinant proteins with post-translational modification, resistance to viral infection and familiarity with drug regulators. However, despite huge progress made in engineering CHO cells for high volumetric productivity, expression of DTE proteins like recombinant lysosomal sulfatase represent one of the poorly understood proteins. Furthermore, there are growing interest in the use of microRNAs (miRNAs) …

Novel Low Shear 3d Bioreactor For The Scaled Production Of High Purity Human Mesenchymal Stem Cells, Andrew Burns

KGI Theses and Dissertations

Human mesenchymal stem cells are an ideal candidate for stem cell therapies. They have been researched since the 1960’s and can differentiate into many desired functional cell types without undergoing teratogenesis. However, higher yields are needed for a marketable, successful stem cell therapy. To accomplish this, cells will have to be cultured to expand them to therapeutically relevant dosages for multiple patients. Bioreactor production is an ideal method to solve this problem.

The aim of this thesis is to test and validate a novel bioreactor for the cultivation of human mesenchymal stem cells. In this work, we investigate a novel …

A Ph-Sensitive Delivery System For The Prevention Of Dental Caries Using Salivary Proteins, Yi Zhu

Electronic Thesis and Dissertation Repository

Dental caries remains one of the most common chronic diseases worldwide. Salivary proteins such as histatins have demonstrated biological functions directly related to tooth homeostasis and prevention of dental caries. However, histatins are susceptible to the high proteolytic activities in the oral environment. Therefore, pH-sensitive chitosan nanoparticles (CNs) have been proposed as potential carriers to target major oral diseases that occur under acidic conditions (e.g. dental caries and dental erosion). Four different types of chitosan polymers were investigated and the optimized CNs successfully loaded histatin 3 and released it selectively under acidic conditions. Through loading the survival time of histatin …