Simple Improvements In Vector Design Afford Substantial Gains In Aav Delivery Of Aggregation-Slowing Aβ Variants, Ella Borgenheimer, Cameron Trueblood, Bryan L Nguyen, William R Lagor, Joanna L Jankowsky

Faculty, Staff and Students Publications

Adeno-associated virus (AAV) gene therapy for neurological disease has gained traction due to stunning advances in capsid evolution for CNS targeting. With AAV brain delivery now in focus, conventional improvements in viral expression vectors offer a complementary route for optimizing gene delivery. We previously introduced a novel AAV gene therapy to slow amyloid aggregation in the brain based on neuronal release of an Aβ sequence variant that inhibited fibrilization of wild-type Aβ. Here we explore three coding elements of the virally delivered DNA plasmid in an effort to maximize the production of therapeutic peptide in the brain. We demonstrate that …

Directed Evolution Of Hedgehog Protein Autoprocessing Activity: Combined Experimental & Computational Approach, Ted Kuke

Undergraduate Honors Theses

Sonic hedgehog protein is vital for embryonic development while also being linked to multiple cancers and holoprosencephaly. The native reaction of hedgehog is a sterolysis reaction whereby cholesterol binds to the HhC catalytic domain and attacks the HhN signaling domain, resulting in a covalent HhN-cholesterol signaling product. The structure of the sterol recognition region (SRR) of Sonic Hedgehog, where cholesterol binds, is currently unknown. In this thesis, I used directed evolution to select a triple mutant of Hedgehog’s catalytic HhC domain, (D46H, Q150H, A196T), which is over 5000 times more catalytically efficient at reacting with epicoprostanol (ECP), a non-native substrate …

Angiogenin-Catalyzed Cleavage Within Trna Anticodon-Loops Identified By Cp-Rna-Seq, Megumi Shigematsu, Ryuma Matsubara, Justin Gumas, Takuya Kawamura, Yohei Kirino

Computational Medicine Center Faculty Papers

Angiogenin (Ang), an endoribonuclease belonging to the RNase A superfamily, cleaves the anticodon-loops of tRNAs to produce tRNA-half molecules. Although previous studies have demonstrated the involvement of Ang in the pathobiology of neurodegenerative disorders, the characterization of Ang-generated tRNA halves in neuronal cells remains limited. This is partly due to the technical limitations of standard RNA-seq methods, which cannot capture Ang-generated RNAs containing a 2',3'-cyclic phosphate (cP). In this report, we established an Ang-treatment model using SH-SY5Y, a human neuroblastoma cell line, and demonstrated Ang-dependent accumulation of tRNA halves. By performing cP-RNA-seq, which selectively captures cP-containing RNAs, we identified Ang-generated …

Host Mediated Rhizobiome Engineering To Develop Locally Adapted Soil Mycorrhizal Inocula To Facilitate The Establishment Of Native Plants On Contaminated Soils, Anna Nugent

Graduate Theses & Non-Theses

The microbial community in the rhizosphere of plants plays an important role in plant establishment and survival, soil stability during stormwater runoff, and potential biofiltration of stormwater. Locally adapted fungal symbionts may further improve these outcomes for native plants at restoration sites. This study assesses the potential of host plant cultured, locally adapted soil mycorrhizal inocula to facilitate the establishment and growth of Mountain Big Sagebrush (Artemisia tridentata subsp. vaseyana) on heavy-metal contaminated soils. Soil was obtained from the rhizosphere of native plants at three sites in the West Side Soils Operable Unit of the Butte, Montana Superfund Complex. One …

Na2B12Si6Se18: A Novel B12-Cluster-Containing Quaternary Selenoborate Framework Material, Gopabandhu Panigrahi, Hunter B. Tisdale, Gregory Morrison, Hans Conrad Zur Loye

Faculty Publications

We report the successful synthesis of the new quaternary, three-dimensional Na₂B₁₂Si₆Se₁₈ material using a solid-state synthesis route. This compound is characterized by a unique framework structure that features the rare icosahedral [B₁₂]¹⁰⁺ cation which is connected via Si2Se6 polyhedral units into a 3D framework structure with Na+ ions located inside the channels. The Na₂B₁₂Si₆Se₁₈ compound crystallizes in the cubic crystal system in the space group Im, with lattice parameter a = 11.91110(10) Å and unit cell volume of 1689.88(4) ų. …

The Role Of Dna Topoisomerases In The Completion Of Dna Replication, Parisa Mokhtari

Dissertations and Theses

Accurate replication of the genome is essential to maintain cellular life. Completing DNA replication on the chromosome is central to this task and involves several enzymes, including RecBCD, RecG and SbcCD-ExoI, which process, join, and resolve the two convergent replication forks. This event is certain to generate a number of structural complexities involving supercoiling, tangles and knots as the two DNA replication forks converge which must be resolved to maintain the integrity of the genome. Structural knots and tangles generated during DNA replication, transcription and segregation are typically resolved by DNA topoisomerases. E. coli encodes four DNA topoisomerases--two type I …

Targeting The Cholesterol Storage Enzyme Acat1/Soat1 In Brain Cells And Mouse Model: A Novel Approach To Address Aging And Apoe4-Related Neuroinflammation, Thao Nguyen Phuong Huynh Krumeich

Dartmouth College Ph.D Dissertations

Alzheimer’s Disease (AD) is a progressive neurodegenerative disease that significantly impacts nearly 7 million people in the United States. AD is characterized by the deposition of amyloid beta (Ab) plaque, tau neurofibrillary tangles (NFTs), lipids granules, and neuroinflammation. Age and apolipoprotein E4 (APOE4) are the two biggest risk factors for AD. Recent AD therapeutic development has mostly benefited the patient population with milder symptoms while causing serious side effects in APOE4 carriers, leaving the most impacted patients’ group - aged APOE4 carriers with no treatment option. With the increasing aging population, there is an urgent need for a …

Differential Infiltration Of Key Immune T-Cell Populations Across Malignancies Varying By Immunogenic Potential And The Likelihood Of Response To Immunotherapy., Islam Eljilany, Sam Coleman, Aik Choon Tan, Martin D. Mccarter, John Carpten, Howard Colman, Abdul Rafeh Naqash, Igor Puzanov, Susanne Arnold, Michelle L. Churchman, Daniel Spakowicz, Bodour Salhia, Julian Marin, Shridar Ganesan, Aakrosh Ratan, Craig Shriver, Patrick Hwu, William S. Dalton, George J. Weiner, Jose R. Conejo-Garcia, Paulo Rodriguez, Ahmad A. Tarhini

Markey Cancer Center Faculty Publications

Background: Solid tumors vary by the immunogenic potential of the tumor microenvironment (TME) and the likelihood of response to immunotherapy. The emerging literature has identified key immune cell populations that significantly impact immune activation or suppression within the TME. This study investigated candidate T-cell populations and their differential infiltration within different tumor types as estimated from mRNA co-expression levels of the corresponding cellular markers.

Methods: We analyzed the mRNA co-expression levels of cellular biomarkers that define stem-like tumor-infiltrating lymphocytes (TILs), tissue-resident memory T-cells (TRM), early dysfunctional T-cells, late dysfunctional T-cells, activated-potentially anti-tumor (APA) T-cells and Butyrophilin 3A (BTN3A) isoforms, utilizing …

D101n: A Unique And Ill-Understood Familial Als-Related Sod1 Mutant, Analisa Lott

Honors Program Theses and Research Projects

Background: Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease, with 90% of documented cases considered sporadic and about 10% showing a hereditary link; such cases are deemed as familial ALS (fALS). Superoxide dismutase (SOD), a copper-zinc binding enzyme that protects cells from damaging free radicals, has been linked to fALS with certain toxic gain of function mutations, such as the D101N mutant. The human SOD1 D101N mutant has been shown to be associated with rapidly progressing neurodegeneration yet is less prone to aggregation than similar mutants, but its deviation from wild-type (WT) SOD1 remains misunderstood.

Objective: Although the D101N …

A Multiplex Metabolomic Approach For Quality Control Of Spirulina Supplement And Its Allied Microalgae (Amphora & Chlorella) Assisted By Chemometrics And Molecular Networking, Nesrine Hegazi, Amira R. Khattab, Hamada H. Saad, Bishoy Abib, Mohamed A. Farag

Faculty Journal Articles

Microalgae species are of economic importance regarded as “green gold” being rich in bioactive compounds. Spirulina and Chlorella are the most popular microalgal species and are marketed as healthy food supplements. At the same time, Amphora holds potential as a source of healthy lipids and essential fatty acids. Yet, there are considerable variations in their reported chemical composition, and less is known about their compositional differences. A multiplexed metabolomic approach was adopted for the quality control (QC) of Spirulina supplements and to compare its constitutive metabolome to Chlorella and Amphora. The adopted protocol comprised gas chromatography-mass spectrometry (GC–MS), ultra-high performance …

Synergistic Anticancer Effect Of Pistacia Lentiscus Essential Oils And 5-Fluorouracil Co-Loaded Onto Biodegradable Nanofibers Against Melanoma And Breast Cancer, Obaydah Abd Alkader Alabrahim, Hassan Mohamed El Said Azzazy

Faculty Journal Articles

Chemoresistance and severe toxicities represent major drawbacks of chemotherapy. Natural extracts, including the essential oils of Pistacia lentiscus (PLEO), exhibit substantial anticancer and anti-inflammatory activities where different cancers are reported to dramatically recess following targeting with PLEO. PLEO has promising antimicrobial, anticancer, and anti-inflammatory properties. However, the therapeutic properties of PLEO are restricted by limited stability, bioavailability, and targeting ability. PLEO nanoformulation can maximize their physicochemical and therapeutic properties, overcoming their shortcomings. Hence, PLEO was extracted and its chemical composition was determined by GC–MS. PLEO and 5-Fluorouracil (5FU) were electrospun into poly-ε-caprolactone nanofibers (PCL-NFs), of 290.71 nm to 680.95 nm …

Ecological And Pathological Applications Of The Heat Shock Response, Taylor Rae Stanley

Theses and Dissertations

The heat shock response (HSR) is a cytoprotective stress response pathway that regulates cellular proteostasis. The HSR is an evolutionarily conserved pathway that is essential for normal cellular functioning. Here, we explore the broad ecological and pathological impacts of the HSR. In an ecological context, we perform gene level analysis of the transcriptomes of two closely related sunfish. We found that the more invasive bluegill sunfish has gene expansions in two HSR gene families, the HSP70 family and the HSP90 family compared to the redear sunfish. These gene expansions were also observed in several other teleost fish species and were …

Synthesis Of Novel Chromenone Esters For Biochemical Assays, Andrew Dean Helmerich

Undergraduate Honors Thesis Collection

This project details the synthesis of a variety of novel chromenone esters to be used as enzymatic probes. A robust, initial library of 22 chromenone esters was successfully synthesized with differences in chain length, branching, and the incorporation of cyclic and heteroatomic moieties. These new chromenones were fully characterized by 1HNMR, 13CNMR, DEPT HRMS, 19FNMR, and HSQC. The utility of these compounds comes from the fact that they will fluoresce upon cleavage of the ester; thus, this property makes them ideal candidates to be used in the monitoring of enzymatic activity of esterases. Elucidating the enzyme-substrate structure activity relationship (SAR) …

Derivation Of A Novel Antimicrobial Peptide From The Red Sea Brine Pools Modified To Enhance Its Anticancer Activity Against U2os Cells, Mona Elradi, Ahmed I. Ahmed, Ahmed M. Saleh, Khaled M.A. Abdel-Raouf, Lina Berika, Yara Daoud, Asma Amleh

Faculty Journal Articles

Cancer associated drug resistance is a major cause for cancer aggravation, particularly as conventional therapies have presented limited efficiency, low specificity, resulting in long term deleterious side effects. Peptide based drugs have emerged as potential alternative cancer treatment tools due to their selectivity, ease of design and synthesis, safety profile, and low cost of manufacturing. In this study, we utilized the Red Sea metagenomics database, generated during AUC/KAUST Red Sea microbiome project, to derive a viable anticancer peptide (ACP). We generated a set of peptide hits from our library that shared similar composition to ACPs. A peptide with a homeodomain …

Polymeric Sumo-2/3 Chain Signals Are Antagonistically Regulated By The Sumo-Targeted Ubiquitin E3 Ligase Rnf4 And The Sumo-Specific Isopeptidase Senp6, Shaniah A. Irving M.A., Xiang-Dong Zhang Ph.D.

Biology Theses

Polymeric SUMO-2/3 chain modification is critical for chromosome segregation, DNA damage repair, genome stability, stress responses, and protein degradation. However, how these signals are regulated remains poorly understood. Both the SUMO-targeted ubiquitin E3 ligase (STUbL) RNF4 and the SUMO-specific isopeptidase SENP6 recognize poly-SUMO-2/3 chains through multiple SUMO-interacting motifs (SIMs). RNF4 contains four tandem SIMs within a short (~80 amino acids) region, whereas SENP6 possesses eight SIMs spanning a much larger (~500 amino acids) domain.

Our preliminary results show that overexpressing an RNF4 N-terminal fragment containing four tandem SIMs (wild type, WT), but not an inactive SIMs mutant (Mut), increases levels …

Decoding Fgf/Fgfr Signaling: Insights Into Biological Functions And Disease Relevance, Oshadi Edirisinghe, Gaetane Ternier, Zeina Alraawi, Thallapuranam Krishnaswamy Suresh Kumar

Chemistry & Biochemistry Faculty Publications and Presentations

Fibroblast Growth Factors (FGFs) and their cognate receptors, FGFRs, play pivotal roles in a plethora of biological processes, including cell proliferation, differentiation, tissue repair, and metabolic homeostasis. This review provides a comprehensive overview of FGF-FGFR signaling pathways while highlighting their complex regulatory mechanisms and interconnections with other signaling networks. Further, we briefly discuss the FGFs involvement in developmental, metabolic, and housekeeping functions. By complementing current knowledge and emerging research, this review aims to enhance the understanding of FGF-FGFR-mediated signaling and its implications for health and disease, which will be crucial for therapeutic development against FGF-related pathological conditions.

Investigation Of Magnesium-Potassium Phosphates As Potential Nuclear Waste Form For The Immobilization Of Minor Actinides, Hans Conrad Zur Loye, Petr Vecernik, Monika Kiselova, Vlastislav Kašpar, Hana Korenkova, Vlastimil Miller, Petr Bezdicka, Jan Šubrt, Natalija Murafa, Volodymyr Shkuropatenko, Sergey Sayenko

Faculty Publications

Several recent studies have evaluated technologies of spent nuclear fuel processing specifically for solidifying transuranic (TRU) waste as a by-product of fission. Of the TRU group, plutonium and the minor actinides will be responsible for the bulk of the radiotoxicity and heat generation of spent nuclear fuel in the long term (300 to 20,000 years). In this study, we investigated magnesium potassium phosphate (MKP)-based compounds as host waste forms for the encapsulation of inactive trivalent Nd and Sm as analogues of the minor trivalent actinides, Am and Cm. Waste forms were fabricated under ambient atmospheric conditions by adding 5 wt.% …

Anti-Inflammatory Potential Of Black Cumin Seed Oil And Its Nanoemulsion Formulation Against Lipopolysaccharide-Induced Liver Injury In Mice, Shady Swidan, Hesham Hafez, Rehab Hosni, Hatem Amin

Pharmacy

Original Article

Anti-inflammatory potential of black cumin seed oil and its nanoemulsion formulation against lipopolysaccharide-induced liver injury in mice

Haffez, Hesham^1,2,✉; Hosni, Rehab³; Swidan, Shady A.⁴; Amin, Hatem K.^1,5

Author Information

¹Biochemistry and Molecular Biology Department, Faculty of Pharmacy, Helwan University, Helwan, 11795, Cairo, Egypt

²Center of Scientific Excellence “Helwan Structural Biology Research”, Helwan University, Helwan, 11795, Cairo, Egypt

³El Sisi Comprehensive Clinic, General Authority for Health Insurance-Giza, Haram, 12556, Giza, Egypt

⁴Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, The British University in Egypt, El-Sherouk, 11837, Cairo, …

Traittrainr: Accelerating Large-Scale Simulation Under Models Of Continuous Trait Evolution, Jenniffer Roa Lozano, Mataya Duncan, Duane D. Mckenna, Todd A. Castoe, Michael Degiorgio, Richard Adams

Entomology and Plant Pathology Faculty Publications and Presentations

Abstract

The scale and scope of comparative trait data are expanding at unprecedented rates, and recent advances in evolutionary modeling and simulation sometimes struggle to match this pace. Well-organized and flexible applications for conducting large-scale simulations of evolution hold promise in this context for understanding models and more so our ability to confidently estimate them with real trait data sampled from nature. Results

We introduce TraitTrainR, an R package designed to facilitate efficient, large-scale simulations under complex models of continuous trait evolution. TraitTrainR employs several output formats, supports popular trait data transformations, accommodates multi-trait evolution, and exhibits flexibility …

Apoa2 Increases Cholesterol Efflux Capacity To Plasma Hdl By Displacing The C-Terminus Of Resident Apoa1, Snigdha Sarkar, Jamie Morris, Youngki You, Hannah Sexmith, Scott E. Street, Stephanie M. Thibert, Isaac K. Attah, Chelsea M. Hutchinson Bunch, Irina V. Novikova, James E. Evans, Amy S. Shah, Scott M. Gordon, Jere P. Segrest, Karin E. Bornfeldt, Tomas Vaisar, Jay W. Heinecke, W. Sean Davidson, John T. Melchior

Saha Cardiovascular Research Center Faculty Publications

Abstract The ability of high-density lipoprotein (HDL) to promote cellular cholesterol efflux is a more robust predictor of cardiovascular disease protection than HDL-cholesterol levels in plasma. Previously, we found that lipidated HDL containing both apolipoprotein A-I (APOA1) and A-II (APOA2) promotes cholesterol efflux via the ATP-binding cassette transporter (ABCA1). In the current study, we directly added purified, lipid-free APOA2 to human plasma and found a dose-dependent increase in whole plasma cholesterol efflux capacity. APOA2 likewise increased the cholesterol efflux capacity of isolated HDL with the maximum effect occurring when equal masses of APOA1 and APOA2 coexisted on the particles. Follow-up …

Untargeted Lipidomics Reveals Novel Hdl Metabotypes And Lipid-Clinical Correlates, Peer W. F. Karmaus, Scott M. Gordon, Marcus Y. Chen, Alison A. Motsinger-Reif, Rodney W. Snyder, Timothy R. Fennell, Suramya Waidyanatha, Reshan A. Fernando, Alan T. Remaley, Michael B. Fessler

Saha Cardiovascular Research Center Faculty Publications

Plasma high-density lipoprotein (HDL), originally studied for its role in lipid transport, is now appreciated to have wide-ranging biological functions that become defective during disease. While >200 lipids have collectively been detected in HDL, published HDL lipidomic analyses in different diseases have commonly been targeted to prespecified subsets of lipids. Here, we report the results of untargeted lipidomic analysis of HDL isolated from 101 subjects referred for computed tomographic coronary imaging for whom multiple additional clinical and lipoprotein metadata were measured. Unsupervised clustering of the total HDL lipidome revealed that the subjects fell into one of two discrete groups, herein …

The Effects Of Mosaicism On Biological And Clinical Markers Of Alzheimer's Disease In Adults With Down Syndrome, Laura Xicota, Lam-Ha T. Dang, Alice Lee, Sharon Krinsky-Mchale, Deborah Pang, Lisa Melilli, Sid E. O’Bryant, Rachel L. Henson, Charles Laymon, Florence Lai, H. Diana Rosas, Beau Ances, Ira Lott, Christy Hom, Bradley Christian, Sigan Hartley, Shahid Zaman, Elizabeth Head, Mark Mapstone, Zhezhen Jin, Wayne Silverman, Nicole Schupf, Benjamin Handen, Joseph H. Lee, Alzheimer’S Biomarker Consortium – Down Syndrome (Abc-Ds)

Neurology Faculty Publications

Background Individuals with Down syndrome (DS) are at high risk of early-onset Alzheimer’s disease (AD); yet, some 20 percent do not develop any signs of dementia until after 65 years or in their lifetime. Mosaicism could contribute to this phenotypic variation, where some disomic cells could lead to lower levels of gene products from chromosome 21.

Methods We examined longitudinal neuropsychological and biomarker data from two large studies of DS: the Alzheimer Biomarker Consortium–Down syndrome study (ABC-DS) (n = 357); and a legacy study (n = 468). We assessed mosaicism using karyotyping or GWAS data. Participants had data on plasma …

Targeted Long-Read Sequencing To Quantify Methylation Of The C9orf72 Repeat Expansion, Evan Udine, Nicole Finch, Mariely Dejesus-Hernandez, Jazmyne L. Jackson, Matthew C. Baker, Siva Arumugam Saravanaperumal, Eric Wieben, Mark T. W. Ebbert, Jaimin Shah, Leonard Petrucelli, Rosa Rademakers, Björn Oskarsson, Marka Van Blitterswijk

Neurology Faculty Publications

Background The gene C9orf72 harbors a non-coding hexanucleotide repeat expansion known to cause amyotrophic lateral sclerosis and frontotemporal dementia. While previous studies have estimated the length of this repeat expansion in multiple tissues, technological limitations have impeded researchers from exploring additional features, such as methylation levels.

Methods We aimed to characterize C9orf72 repeat expansions using a targeted, amplification-free long-read sequencing method. Our primary goal was to determine the presence and subsequent quantification of observed methylation in the C9orf72 repeat expansion. In addition, we measured the repeat length and purity of the expansion. To do this, we sequenced DNA extracted from …

Characterization Of The Final Enzyme In The Coenzyme M Biosynthesis Pathway In Methanosarcina, Connor John Hines

Dissertations and Doctoral Documents, University of Nebraska-Lincoln, 2023–

Methanogenesis is known to be one of the oldest forms of energy generation on our planet. Methanogens rely on this method of energy conservation and have evolved to metabolize a variety of substrates, including the waste products of other organisms. This feature has made methanogens beneficial to both wastewater treatment and landfill-to-energy projects. Methane itself is a greenhouse gas twenty times more potent than carbon dioxide, viewed as a particularly influential contributor to global greenhouse emissions. Climate change was known to be on the horizon throughout the 20^th century but has made itself known vocally during this 21^{st …}

Cross-Interactions Of Amyloid Proteins: Implications For Aggregation Dynamics And Disease Pathology, Zhiyuan Song

All Dissertations

Amyloid aggregation is a pervasive form of protein misfolding implicated in the pathology of several prominent human diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), and type 2 diabetes (T2D). These diseases are marked by the accumulation of amyloid fibrils and toxic oligomers, which are highly dynamic and heterogeneous, posing challenges for understanding their roles in disease progression. Despite significant advances in the diagnosis and management of these conditions, no definitive cure is available. We investigate amyloid aggregation and cross-seeding, with a focus on amyloid-beta (Aβ), tau, alpha-synuclein (αS), and human islet amyloid polypeptide (IAPP) through discrete molecular dynamics (DMD) …

Functionalized Carbon Quantum Dots: A Promising Nanomaterial For Investigating Their Potential In Neurodegenerative Disease Treatment, Sherin M. El Morsy

Open Access Theses & Dissertations

Neurodegenerative diseases such as Parkinson's Disease (PD), Alzheimer's Disease (AD), and Huntington's Disease (HD) remain incurable, despite extensive research into therapeutic development. In the United States of America, the annual cost of PD and AD in terms of patient care and lost productivity is approximately $200 billion. Consequently, there is a critical and unaddressed need for the development of innovative drugs and drug delivery systems that can decelerate, stop, or ideally reverse neurodegenerative diseases. The dissertation presented here focuses on devising strategies to target PD through multiple mechanisms, including the inhibition of protein aggregation and the reduction of oxidative stress. …

Tc-Ptp-Mediated Regulation Of P38 Mapk Pathway Promotes Uvb-Induced Apoptosis In Skin, Lindsey Susie Shim

Theses and Dissertations

T-cell protein tyrosine phosphatase (TC-PTP) is a non-receptor PTP that has been shown to have various roles in signaling pathways. Our previous studies have demonstrated that the TC-PTP deficiency in the epidermis can exacerbate hyperplastic response by inducing epidermal cell proliferation in response to tumor promoter TPA or UVB exposure. This implies that TC-PTP plays a tumor-suppressive role in the epidermis and provides protection against UVB radiation, which is well known to contribute to skin cancer development. The p38 mitogen-activated protein kinase (MAPK) is one of serine/threonine kinases that are activated through environmental stress including UVB. It has been demonstrated …

Effect Of An Anti-Hiv Polymer Based Nanoformulation On Immune Mediating Cells Within The Gut Associated Lymphoid Tissue And Its Behavioural Impacts, Blessed Ofori

Theses and Dissertations

This thesis investigates the therapeutic potential of nanoformulated antiretroviral therapy (NF cART) and its implications for HIV-associated chronic inflammation and neurobehavioral outcomes. In the first study, NF cART demonstrated enhanced efficacy in modulating inflammasome activation and reducing viral reservoirs in gut-associated lymphoid tissue (GALT) and the small intestine of HIV-infected humanized mice. Key markers of inflammation (NLRP3, Caspase-1, and IL-1β) and viral replication (LTR and p24 levels) were significantly suppressed with NF cART compared to conventional therapy, though residual LTR expression persisted in the small intestine. In the second study, nanoformulated Emtricitabine uniquely enhanced locomotor activity and reduced anxiety-like behaviors …

Physicochemical Property Effects On Immune Modulating Polymeric Nanoparticles: Potential Applications In Spinal Cord Injury, Daniel J. Kolpek, Jaechang Kim, Hisham Mohammed, John C. Gensel, Jonghyuck Park

Markey Cancer Center Faculty Publications

Nanoparticles (NPs) offer promising potential as therapeutic agents for inflammation-related diseases, owing to their capabilities in drug delivery and immune modulation. In preclinical studies focusing on spinal cord injury (SCI), polymeric NPs have demonstrated the ability to reprogram innate immune cells. This reprogramming results in redirecting immune cells away from the injury site, downregulating pro-inflammatory signaling, and promoting a regenerative environment post-injury. However, to fully understand the mechanisms driving these effects and maximize therapeutic efficacy, it is crucial to assess NP interactions with innate immune cells. This review examines how the physicochemical properties of polymeric NPs influence their modulation of …

Independent Evolution Of Oleate Hydratase Clades In Bacillales Reflects Molecular Convergence, Robert J. Neff, Priscilla C. Lages, Shannon K. Donworth, James D. Brien, Christopher D. Radka

Markey Cancer Center Faculty Publications

Oleate hydratase (OhyA), a flavoenzyme that catalyzes the hydration of unsaturated fatty acids, has been identified in various Bacillales organisms, including those in the Listeria, Lysinibacillus, Paenibacillus, and Staphylococcus genera. In this study, we combine structural biology with molecular and phylogenetic analyses to investigate the evolutionary dynamics of the OhyA protein family within the Bacillales order. Our evolutionary analysis reveals two distinct OhyA clades (clade I and clade II) within Bacillales that, while sharing catalytic function, exhibit significant genomic and structural differences. Our findings suggest that these OhyA clades originated from independent evolutionary processes through convergent evolution rather than gene …