Digital Commons Network^™

Cooperative Nucleic Acid Binding By Poly Adp‑Ribose Polymerase 1, Manana Melikishvili, Michael G. Fried, Yvonne N. Fondufe‑Mittendorf

Markey Cancer Center Faculty Publications

Poly (ADP)‑ribose polymerase 1 (PARP1) is an abundant nuclear protein well‑known for its role in DNA repair yet also participates in DNA replication, transcription, and co‑transcriptional splicing, where DNA is undamaged. Thus, binding to undamaged regions in DNA and RNA is likely a part of PARP1’s normal repertoire. Here we describe analyses of PARP1 binding to two short single‑stranded DNAs, a single‑stranded RNA, and a double stranded DNA. The investigations involved comparing the wild‑ type (WT) full‑length enzyme with mutants lacking the catalytic domain (∆CAT) or zinc fingers 1 and 2 (∆Zn1∆Zn2). All three protein types exhibited monomeric characteristics in …

Non-Transcriptional Irf7 Interacts With Nf-Κb To Inhibit Viral Inflammation, Shumin Fan, Sonam Popli, Sukanya Chakravarty, Ritu Chakravarty, Saurabh Chattopadhyay

Markey Cancer Center Faculty Publications

Interferon (IFN) regulatory factors (IRF) are key transcrip- tion factors in cellular antiviral responses. IRF7, a virus- inducible IRF, expressed primarily in myeloid cells, is required for transcriptional induction of interferon α and antiviral genes. IRF7 is activated by virus-induced phosphory- lation in the cytoplasm, leading to its translocation to the nu- cleus for transcriptional activity. Here, we revealed a nontranscriptional activity of IRF7 contributing to its antiviral functions. IRF7 interacted with the pro-inflammatory tran- scription factor NF-κB-p65 and inhibited the induction of in- flammatory target genes. Using knockdown, knockout, and overexpression strategies, we demonstrated that IRF7 inhibited NF-κB–dependent inflammatory …

Foxs1 Is Increased In Liver Fibrosis And Regulates Tgfβ Responsiveness And Proliferation Pathways In Human Hepatic Stellate Cells, Evelyn A. Bates, Zachary A. Kipp, Wang-Hsin Lee, Genesee J. Martinez, Lauren Weaver, Kathryn N. Becker, Sally Pauss, Justin F. Creeden, Garrett B. Anspach, Robert N. Helsley, Mei Xu, Maria E. C. Bruno, Marlene E. Starr, Terry D. Hinds Jr.

Markey Cancer Center Faculty Publications

Liver fibrosis commences with liver injury stimulating transforming growth factor beta (TGFβ) activation of hepatic stellate cells (HSCs), causing scarring and irreversible damage. TGFβ induces expression of the transcription factor Forkhead box S1 (FOXS1) in hepatocytes and may have a role in the pathogenesis of hepatocellular carcinoma (HCC). To date, no studies have determined how it affects HSCs. We analyzed human livers with cirrhosis, HCC, and a murine fibrosis model and found that FOXS1 expression is significantly higher in fibrotic livers but not in HCC. Next, we treated human LX2 HSC cells with TGFβ to activate fibrotic pathways, and FOXS1 …

Nac1 Promotes Stemness And Regulates Myeloid-Derived Cell Status In Triple-Negative Breast Cancer, Chrispus Ngule, Ruyi Shi, Xingcong Ren, Hongyan Jia, Felix Oyelami, Dong Li, Younhee Park, Jinhwan Kim, Hami Hemati, Yi Zhang, Xiaofang Xiong, Andrew Shinkle, Nathan L. Vanderford, Sara Bachert, Binhua P. Zhou, Jianlong Wang, Jianxun Song, Xia Liu, Jin-Ming Yang

Markey Cancer Center Faculty Publications

Triple negative breast cancer (TNBC) is a particularly lethal breast cancer (BC) subtype driven by cancer stem cells (CSCs) and an immunosuppressive microenvironment. Our study reveals that nucleus accumbens associated pro- tein 1 (NAC1), a member of the BTB/POZ gene family, plays a crucial role in TNBC by maintaining tumor stemness and influencing myeloid-derived suppressor cells (MDSCs). High NAC1 expression correlates with worse TNBC prognosis. NAC1 knockdown reduced CSC markers and tumor cell proliferation, migration, and invasion. Addition- ally, NAC1 affects oncogenic pathways such as the CD44-JAK1-STAT3 axis and immunosuppressive signals (TGFβ, IL-6). Intriguingly, the impact of NAC1 on tumor …

Mir-27a-3p Regulates Intestinal Cell Proliferation And Differentiation Through Wnt/Β-Catenin Signalling, Chang Li, Yuning Zhou, Yinping Jiang, Zhijie Yin, Heidi L. Weiss, Qingding Wang, B. Mark Evers

Markey Cancer Center Faculty Publications

Intestinal stem cells differentiate into absorptive enterocytes, characterised by increased brush border enzymes such as intestinal alkaline phosphatase (IAP), making up the majority (95%) of the terminally differentiated cells in the villus. Loss of integ- rity of the intestinal epithelium plays a key role in inflammatory diseases and gastro- intestinal infection. Here, we show that the intestinal microRNA (miR)-27a-3p is an important regulator of intestinal epithelial cell proliferation and enterocyte differenti- ation. Repression of endogenous miR-27a-3p leads to increased enterocyte differen- tiation and decreased intestinal epithelial cell proliferation in mouse and human small intestinal organoids. Mechanistically, miR-27a-3p regulates intestinal cell …

Interactions Between Multiple Stressors, Nanomaterials And A Pathogen, In Caenorhabditis Elegans, Jarad Cochran

Theses and Dissertations--Plant and Soil Sciences

Metal and metal oxide nanoparticles (NP), which have received interest for use in agriculture, show in vitro and in vivo toxicity at relatively low concentrations. Silver nanoparticles (Ag NP) and zinc oxide nanoparticles (ZnO NP) cause adverse effects in model soil organisms under environmentally relevant conditions. In most toxicity assessments of nanomaterials, model organisms are exposed to a single stressor. Though single stressor experiments are essential to understanding the fate and effects of released NP, in nature, organisms are affected by multiple stressors, including pathogens, which might exacerbate or mitigate negative effects of NP exposure. There is limited research on …

Cross-Layer Design Of Highly Scalable And Energy-Efficient Ai Accelerator Systems Using Photonic Integrated Circuits, Sairam Sri Vatsavai

Theses and Dissertations--Electrical and Computer Engineering

Artificial Intelligence (AI) has experienced remarkable success in recent years, solving complex computational problems across various domains, including computer vision, natural language processing, and pattern recognition. Much of this success can be attributed to the advancements in deep learning algorithms and models, particularly Artificial Neural Networks (ANNs). In recent times, deep ANNs have achieved unprecedented levels of accuracy, surpassing human capabilities in some cases. However, these deep ANN models come at a significant computational cost, with billions to trillions of parameters. Recent trends indicate that the number of parameters per ANN model will continue to grow exponentially in the foreseeable …

Nonuniform Sampling-Based Breast Cancer Classification, Santiago Posso

Theses and Dissertations--Electrical and Computer Engineering

The emergence of deep learning models and their success in visual object recognition have fueled the medical imaging community's interest in integrating these algorithms to improve medical diagnosis. However, natural images, which have been the main focus of deep learning models and mammograms, exhibit fundamental differences. First, breast tissue abnormalities are often smaller than salient objects in natural images. Second, breast images have significantly higher resolutions but are generally heavily downsampled to fit these images to deep learning models. Models that handle high-resolution mammograms require many exams and complex architectures. Additionally, spatially resizing mammograms leads to losing discriminative details essential …

The Effect Of A Community Resiliency Model Education On Resilience, Psychological Empowerment, And Well-Being In Behavioral Health Nurses, Lorrie Smith-Esterle

DNP Projects

Background: Resilience, well-being, and psychological empowerment are associated with improvement in job satisfaction and nurse retention rates. The Community Resiliency Model (CRM) can promote emotional regulation, well-being, and create an internal state of balance in response to work-related stressors. Educating nurses on how to use CRM enables the recognition of changes in thoughts, emotions, sensations, and internal or external stimuli, which can promote resilience, well-being, and psychological empowerment.

Purpose: The purpose of this project was to evaluate evaluate the effect of a resiliency education using the Community Resiliency Model (CRM) on resilience, psychological empowerment, and well-being of behavioral health nurses. …

Evaluation Of Winter Cereal Cover Crops Across Nitrogen Management Strategies In No-Till Corn Production, Robert Nalley

Theses and Dissertations--Plant and Soil Sciences

Rye (Secale cereale L.) is the most popular winter cereal cover crop utilized before corn, but wheat (Triticum aestivum L.) and barley (Hordeum vulgare L.) may provide a comparable value due to their similar fibrous root systems. Despite the benefits associated with winter cereal cover crops, drawbacks are possible for the subsequent corn crop. A field study was conducted with three site-years in Kentucky to measure the impact of the three winter cereals across nitrogen (N) management strategies. Wheat produced the most biomass compared with barley or rye cover crops. Wheat and rye needed approximately 100 more …

From Code To Crops: Harnessing Bioinformatics And Artificial Intelligence (Ai) In Agricultural Omics, Lakshay Anand

Theses and Dissertations--Plant and Soil Sciences

Global agricultural faces numerous challenges, such as climate change, resource limitations, novel pests and diseases, increasing costs, and the ever-increasing human population. To tackle these challenges, we need innovative strategies that combine new technologies and data analytics approaches to enhance agricultural output, promote sustainable methods, and optimize resource allocation. The key to this innovation lies in understanding the complex molecular web within plants that governs their growth, defense, and adaptability mechanisms. By mastering this molecular network, we can cultivate crops that are more resilient, sustainable, and suitable for different climatic terrains. Moreover, studying the symbiotic relationship between plants and microorganisms …

The Effects Of Potassium Fertilization Regime On High Tunnel Tomato Production, Sapana Pandey

Theses and Dissertations--Plant and Soil Sciences

A two-year field experiment (2022-2023) was conducted at the University of Kentucky Horticulture Research Farm in Lexington, KY to study the effects of potassium (K2O) fertilization rates on tomato yield and ripening disorders in determinate and indeterminate varieties (‘BHN-589’ and ‘Big Beef’, respectively). In the first year, K2O rates representing the soil test result-based commercial recommendation (0 lbs/acre) and sequentially greater rates (150, 300, and 450 lbs K2O/acre) were applied. In the second year, K2O rates were increased based on lack of fruit quality response and were 0, 300, 600, and 900 lbs K2O/acre. Leaf tissue nutrients, tomato yield, and …

Surveys, Field Studies, And Laboratory Incubation Experiments To Improve Alfalfa Production In The Mid-South, William Fleming

Theses and Dissertations--Plant and Soil Sciences

The objective of the alfalfa survey was to determine the role of soil fertility in the alfalfa yield plateau. Soil samples at depths of 10, 15, and 30 cm and tissue samples were collected from 114 alfalfa stands across Kentucky and surrounding states. Results indicate that soil fertility is likely contributing but not driving the alfalfa yield plateau. The main objective of the polyhalite incubation study is to determine if POLY4 was soluble enough to support potassium (K) and sulfur (S) for plant growth. The design of the study included four fertilizer treatments, three soil types, and four incubation times. …

Identifying Physiological, Morphological, And Genetic Drivers Of Key Intermediary Phenotypic Traits Associated With Stalk Lodging Resistance Within Genetically Diverse Maize Germplasm And Sorghum, Norbert Bokros

Theses and Dissertations--Plant and Soil Sciences

Maize stalk lodging reduces grain yields due to the permanent breakage or deformation of stalk tissue before grain harvest. To reveal new insights into the complex problem of maize stalk lodging, this dissertation will examine three primary objectives. First, the direct, diurnal influence of turgor pressure will be shown to have only marginal effects on stalk bending strength, a key trait associated with stalk lodging resistance. Up to a dozen individual stalks, grown to physiological maturity within the same field, were tested using a DARLING testing device. In parallel, stalk turgor status as measured by leaf water potential and turgor …

The Effect Of Spring And Winter Killed Cover Crops On Soil Physical Properties And Soil Organic Carbon, Danielle Doering

Theses and Dissertations--Plant and Soil Sciences

Maintaining soil organic carbon (SOC) and healthy soil physical structure in agroecosystems is crucial to sustainable production. To assess medium term impacts of cover crops on soil health in the top 90 cm, we conducted a field experiment in central Kentucky with varying levels of winter cover: spring and winter kill cover crops, weedy and bare winter fallows. After eight years of cover crop use, some soil physical properties improved: 35% greater mean weight aggregate diameter at 0-30 cm with spring kill covers and 5.2% more C held within large aggregates for both cover crop treatments compared to winter fallow. …

The Roles Of Mrna Polyadenylation Factors In Plant Growth And Development, Lichun Zhou

Theses and Dissertations--Plant and Soil Sciences

Messenger RNA polyadenylation, the process wherein the primary RNA polymerase II transcript is cleaved and a poly(A) tract added, is a key step in the expression of genes in plants. Polyadenylation is mediated by a complex (the polyadenylation complex, or PAC) that consists of between 15 and 20 subunits. To learn the roles of PAC in regulation of the polyadenylation in plants, I conducted a survey of variability in the plant PAC. For this, I drew upon a database of naturally-occurring variation in numerous geographic isolates of Arabidopsis thaliana. The results show that many subunits of the PAC are …

Functionalized Microfiltration Membranes For Aerosol Capture To Chloro-Organic Degradation, Rollie George Mills

Theses and Dissertations--Chemical and Materials Engineering

The environmental remediation of water and air sources is a challenging field, due to widespread contamination, pollutant variety, and efficiency of existing treatment options. Remediation of certain pollutants, such as per- and polyfluorinated chemicals (PFAS), polychlorinated biphenyls (PCBs), volatile organic compounds (VOCs), and viral aerosols, has shown promise via adsorptive, degradative, or filtration-based processes, each with their respective advantages and limitations. Membrane technology is one option that has exhibited considerable pollutant removal from environmental sources via reverse osmosis (RO) filtration, but is limited by low permeabilities and lack of pollutant detoxification. With the support of NIEHS and NSF, the functionalization …

Development Of Glutathione-Responsive Disulfide-Containing Poly(Beta-Amino Esters) With Varied Hydrophilicity And Acrylate Functionality, Anastasiia Aronova

Theses and Dissertations--Chemical and Materials Engineering

Smart biomaterials are becoming promising for therapeutic deliveries due to their ability to respond to changes in the environment. Redox-responsive hydrogels are a promising type of smart polymer that can swell and degrade according to cellular oxidative stress levels. Glutathione, abundant in cells, is crucial in redox-responsive biomaterials, serving as a key reactive molecule. This study explored the degradation kinetics of glutathione-responsive poly(β-amino ester) (PBAE) polymers created through a single-step Michael addition. We examined how disulfide content influences the degradation kinetics of these PBAE networks. Additionally, we investigated how the hydrophilicity and functionality of acrylate affect the degradation of disulfide-containing …

Faceting Of Tungsten Via Environmental Control Of Temperature, Pressure And Chemistry, And Evolution Of Thermionic Cathode Materials, Huanhuan Bai

Theses and Dissertations--Chemical and Materials Engineering

Scandate cathode presents a great potential of being used as electron emitters in vacuum electron device due to its excellent emission performance. However, it is burdened by several issues, including poor emission uniformity, inadequate reproducibility, and limited lifetime, which have impeded its further industrial application. Therefore, extensive efforts and studies need to be conducted to obtain a more comprehensive understanding of scandate cathode.

W particles, as the base material, play a fundamental role in scandate cathode. Most recent experimental research has reported that the highly faceted crystallography of W grains contributes to the properties of scandate cathode. In order to …

Experimental Characterization And Quantification Of Deformation Behavior In A Porous Carbon Fiber Network, Robert N Quammen

Theses and Dissertations--Chemical and Materials Engineering

Due to their wide range of attractive functional properties (such as low thermal conductivity and low density) porous materials are utilized in a variety of applications. In order to characterize these properties and others, the intrinsically heterogeneous microstructures of these materials need to be taken into account. These microstructures result in interactions across multiple length scales spanning several orders of magnitude. This makes the creation of robust computational models and straight-forward predictions of mechanical properties difficult for porous materials. With this in mind, this dissertation aims to provide experimental mechanical and deformation information spanning the length scales of interest for …

Single-Atom Catalysts For Electrochemical Energy Conversion: Copper Single-Atom Catalyst For Oxygen Reduction Reaction And Quantification Of Site Density By Co Stripping Voltammetry, Dawatage Perera

Theses and Dissertations--Chemistry

Fuel cells are considered a promising technology for achieving cleaner and more sustainable energy production and utilization. However, one of the current major challenges is the economic viability associated with the extensive use of Pt group metal (PGM) catalysts, particularly on the cathode side. Therefore, non-PGM single-atom catalysts (SACs) have received considerable attention as alternatives for PGM catalysts in the oxygen reduction reaction (ORR), which occurs at the cathode of the fuel cell. Among various SAC structures, the non-PGM/nitrogen-doped carbon-based structure (M-N-C) stands out for its excellent ORR performance.

Chapter 2 illustrates the use of copper metal in place of …

Synthetic Strategies Toward The Development Of Stable Gold-Based Anticancer Agents And Their Mechanistic Insight, Adedamola Arojojoye

Theses and Dissertations--Chemistry

Despite notable advancements in the design and synthesis of novel chemotherapeutic drugs, cancer continues to be a leading cause of death in the United States. Metallodrugs, especially Au complexes, have played a prominent role in the search for the next generation of chemotherapeutic agents. Herein, I report on the synthetic strategies towards the rational design of stable Au (Au)-based agents, study their reactivity in biological environment, and offer insights into the cytotoxic mechanism of action in cancer. Chemotherapeutic Au compounds exist mainly in +I or +III oxidation states. Repurposing of the Au(I) FDA approved auranofin for the treatment of diseases …

Synthesis, Functionalization, And Application Of Polymeric Membrane Blends Of Polysulfone, Poly-Ether Ether-Ketone, And Natural Fiber Additive Biochar For Optimal Water Treatment., Abelline Katusiime Fionah

Theses and Dissertations--Chemistry

According to the Center for disease control (CDC), an estimated 1.7 to 2.2 million persons die from waterborne diseases annually. The majority of individuals dying from diseases resulting from unsafe drinking water, such as diarrhea and gastroenteritis, are children. This has in turn created a global water crisis. Different methods have been developed to treat contaminated water in response to the global water crisis such as adsorption, filtration, ozonolysis, catalysis, etc. Of the methods available, filtration via polymeric membranes has been one of the most successfully applied. A membrane is a thin semi-permeable barrier (often made of a polymer) used …

Investigating Dynamics Of Electron Transfer Flavoprotein And Its Partner Flavodoxin Via Small Angle Neutron Scattering And Fluorine Nmr, Sharique Ahmad Khan

Theses and Dissertations--Chemistry

Anaerobic bacteria and archaea thrive in seemingly inhospitable environments because they are extremely energy efficient. Their capacity to fully utilize electrochemical energy is based in large part on their ability to conduct electron transfer bifurcation ('bifurcation') at strongly reducing potentials, thereby producing extremely potent reducing agents able to fix nitrogen and make molecular hydrogen. This chemistry is made possible by the use of a flavin as the site of bifurcation, supported by a specialized protein environment and mechanisms that control the flow of individual electrons.

Bifurcating electron transfer flavoproteins (Bf-ETFs) are versatile protein modules that provide the bifurcating capability associated …

Investigating The Behavior Of Redox–Active Organic Molecules In Electrochemical Energy Storage Through Experiment–Guided Computational Simulations, Anton Perera

Theses and Dissertations--Chemistry

The long–anticipated implementation of using renewable sources such as solar and wind to meet the world’s energy demand is still limited by not having appropriate grid–level energy storage systems on a global scale. When considering grid–scale energy storage solutions, environmental concerns, and techno–economic viability play a crucial role in the practical implementation of such technology. To address this, redox–active organic molecules (ROMs) have been explored for many uses including serving as redox–active molecules in redox flow batteries (RFBs) and providing overcharge protection in lithium–ion batteries (LIBs).

Nevertheless, in order to be a major player in electrochemical energy storage, further optimization …

Gender Differences In Preschool Conduct Disorder Symptoms Across One-Year, Madeline K. Petersen

Theses and Dissertations--Psychology

Conduct disorder is a childhood disruptive behavior disorder that exhibits striking gender differences in prevalence, comorbidities, and associated outcomes. These gender differences, particularly symptomology, remain understudied in conduct disorder despite the growing prevalence in females. This paper seeks to examine gender differences in parent rated conduct disorder symptoms in preschoolers overrecruited for disruptive behavior problems at three different timepoints across one-year. It is hypothesized that males will exhibit higher levels of physical aggression symptoms at the initial timepoint with declining rates across a one-year period compared to females, while females will exhibit lower levels of conduct problems at the first …

Ergot Alkaloid Consumption Alters Serotonin Receptor-Induced Vasoactivity In Ovine Umbilical Vasculature, James L. Klotz, Jessica L. Britt, Maslyn A. Greene, Coral Kent-Dennis, Susan K. Duckett

Animal and Food Sciences Faculty Publications

Consumption of ergot alkaloids during the second half of gestation has been shown to decrease umbilical artery vasoactivity resulting in decreased birth weights. Negative vascular effects of ergot alkaloids are mediated predominantly through serotonergic and adrenergic receptors in other tissues. Vasoactivity of serotonin (5-HT) receptors 5-HT_2A and 5-HT_1B/1D in umbilical artery and vein from ewes receiving endophyte-infected seed (E + 1.77 mg ergovaline/hd/d) or a control total mixed ration (CON; 0 mg ergovaline/hd/d) tall fescue seed at d-110 and d-133 of gestation was evaluated. Gravid reproduction tracts were collected from ewes. Two-mm sections of umbilical artery and vein …

Essential Oil Supplementation Improves Insulin Sensitivity And Modulates The Plasma Metabolome Of Hyperinsulinemic Horses, Caroline M.M. Loos, Shuang Zhao, Liang Li, Janet Li, Wei Han, Eric S. Vanzant, Kyle R. Mcleod

Animal and Food Sciences Faculty Publications

The objective of this study was to investigate the effect of essential oil (EO) supplementation on insulin sensitivity (IS) and the plasma metabolome in insulin dysregulated (ID) horses. Horses were blocked by degree of IS and assigned randomly to treatment: oral daily bolus (50 mL) of either a plant derived EO supplement or carrier (CON). Mares were housed in dry lots with ad libitum access to grass hay and supplemented individually twice daily with a concentrate to meet nutrient requirements for mature horses. Before and after 6 wks of treatment, mares underwent a combined glucose-insulin tolerance test (CGIT) and an …

Ovotransferrin-Depleted Egg White Hydrolysate Reduces Blood Pressure In Spontaneously Hypertensive Rats, Fatemeh Ashkar, Hongbing Fan, Zihan Wang, Ilekuttige Priyan Shanura Fernando, Jianping Wu

Animal and Food Sciences Faculty Publications

Egg whites contain a variety of biologically active proteins and are a good source of bioactive peptides. Egg white hydrolysate prepared by thermoase (EWH) possesses antihypertensive effects. Our recent study showed that egg white proteins, after depleting ovotransferrin, also contained many angiotensin-converting enzyme (ACE)-inhibitory peptides after hydrolysis using thermoase. In the present study, we aimed to explore the antihypertensive effect of the ovotransferrin-depleted egg white hydrolysate prepared by thermoase (OD-EWH) in spontaneously hypertensive rats, using EWH as the reference. The animals were orally administered with either hydrolysate at a dose of 1 g/kg body weight/d over 9 d. OD-EWH treatment …

Effects Of A Second Iron-Dextran Injection Administered To Piglets During Lactation On Differential Gene Expression In Liver And Duodenum At Weaning, James L. Pierce, J. Wesley Lyons, Tyler B. Chevalier, Merlin D. Lindemann

Animal and Food Sciences Faculty Publications

Six female littermate piglets were used in an experiment to evaluate the mRNA expression in tissues from piglets given one or two 1 mL injections of iron dextran (200 mg Fe/mL). All piglets in the litter were administered the first 1 mL injection < 24 h after birth. On day 7, piglets were paired by weight (mean body weight = 1.72 ± 0.13 kg) and one piglet from each pair was randomly selected as control (CON) and the other received a second injection (+Fe). At weaning on day 22, each piglet was anesthetized, and samples of liver and duodenum were taken from the anesthetized piglets and preserved until mRNA extraction. differential gene expression data were analyzed with a fold change cutoff (FC) of |1.2| P < 0.05. Pathway analysis was conducted with Z-score cutoff of P < 0.05. In the duodenum 435 genes were significantly changed with a FC ≥ |1.2| P < 0.05. In the duodenum, Claudin 1 and Claudin 2 were inversely affected by + Fe. Claudin 1 (CLDN1) plays a key role in cell-to-cell adhesion in the epithelial cell sheets and was upregulated (FC = 4.48, P = 0.0423). Claudin 2 (CLDN2) is expressed in cation leaky epithelia, especially during disease or inflammation and was downregulated (FC = -1.41, P = 0.0097). In the liver, 362 genes were expressed with a FC ≥ |1.2| P < 0.05. The gene most affected by a second dose of 200 mg Fe was hepcidin antimicrobial peptide (HAMP) with a FC of 40.8. HAMP is a liver-produced hormone that is the main circulating regulator of Fe absorption and distribution across tissues. It also controls the major flows of Fe into plasma by promoting endocytosis and degradation of ferroportin (SLC4A1). This leads to the retention of Fe in Fe-exporting cells and decreased flow of Fe into plasma. Gene expression related to metabolic pathway changes in the duodenum and liver provides evidence for the improved feed conversion and growth rates in piglets given two iron injections preweaning with contemporary pigs in a companion study. In the duodenum, there is a downregulation of gene clusters associated with gluconeogenesis (P < 0.05). Concurrently, there was a decrease in the mRNA expression of genes for enzymes required for urea production in the liver (P < 0.05). These observations suggest that there may be less need for gluconeogenesis, and possibly less urea production from deaminated amino acids. The genomic and pathway analyses provided empirical evidence linking gene expression with phenotypic observations of piglet health and growth improvements.