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Articles 91 - 120 of 439

Full-Text Articles in Cell and Developmental Biology

Regulated Translocation Of Neutral Sphingomyelinase-2 To The Plasma Membrane Drives Insulin Resistance In Steatotic Hepatocytes, Salim S. El-Amouri, Alexander A. Karakashian, Erhard Bieberich, Mariana N. Nikolova‑Karakashian Oct 2023

Regulated Translocation Of Neutral Sphingomyelinase-2 To The Plasma Membrane Drives Insulin Resistance In Steatotic Hepatocytes, Salim S. El-Amouri, Alexander A. Karakashian, Erhard Bieberich, Mariana N. Nikolova‑Karakashian

Markey Cancer Center Faculty Publications

Abstract Obesity-associated diabetes is linked to the accumulation of ceramide in various organs, including the liver. The exact mechanisms by which ceramide contributes to diabetic pathology are unclear, but one proposed scenario is that ceramide accumulation may inhibit insulin signaling pathways. It is unknown however whether the excess ceramide is generated proximal to the insulin receptor, that is, at the plasma membrane (PM), where it could affect the insulin signaling pathway directly, or the onset of insulin resistance is due to ceramide- induced mitochondrial dysfunction and/or lipotoxicity. Using hepatic cell lines and primary cultures, gain- and loss- of function approach, …


Canine Testes Thin Sections Culture​, Nguyen Khoi Nguyen, Ramanpreet Singh Sep 2023

Canine Testes Thin Sections Culture​, Nguyen Khoi Nguyen, Ramanpreet Singh

2023 Symposium

Canine testes thin section culture

Testes tissue culture systems would provide a tool to elucidate spermatogenesis mechanisms, with the aim of genetic preservation of mammals, especially endangered species. Our experiment aims to develop a culture system capable of producing viable mammalian sperm cells in vitro.

Dogs were chosen as the model organism because testes are readily available. Canine testes were obtained from a local veterinary clinic. Thin sections were generated using a commercial electric slicer. They then were cleaned using Dulbecco’s Phosphate-Buffered Saline (DPBS) supplemented with antibiotics then cultured in a modified Tissue Culture Medium 199 (TCM-199). Sections were …


Canine Testes Thin Sections Culture, Nguyen Khoi Nguyen, Ramanpreet Singh Sep 2023

Canine Testes Thin Sections Culture, Nguyen Khoi Nguyen, Ramanpreet Singh

2023 Symposium

Canine testes thin section culture

Testes tissue culture systems would provide a tool to elucidate spermatogenesis mechanisms, with the aim of genetic preservation of mammals, especially endangered species. Our experiment aims to develop a culture system capable of producing viable mammalian sperm cells in vitro.

Dogs were chosen as the model organism because testes are readily available. Canine testes were obtained from a local veterinary clinic. Thin sections were generated using a commercial electric slicer. They then were cleaned using Dulbecco’s Phosphate-Buffered Saline (DPBS) supplemented with antibiotics then cultured in a modified Tissue Culture Medium 199 (TCM-199). Sections were …


Asparagine Restriction Enhances Cd8+ T Cell Metabolic Fitness And Antitumoral Functionality Through An Nrf2-Dependent Stress Response, J. N. Rashida Gnanaprakasam, Bhavana Kushwaha, Lingling Liu, Xuyong Chen, Siwen Kang, Tingting Wang, Teresa A. Cassel, Christopher M. Adams, Richard M. Higashi, David A. Scott, Gang Xin, Zihai Li, Jun Yang, Andrew N. Lane, Teresa Whei-Mei Fan, Ji Zhang, Ruoning Wang Aug 2023

Asparagine Restriction Enhances Cd8+ T Cell Metabolic Fitness And Antitumoral Functionality Through An Nrf2-Dependent Stress Response, J. N. Rashida Gnanaprakasam, Bhavana Kushwaha, Lingling Liu, Xuyong Chen, Siwen Kang, Tingting Wang, Teresa A. Cassel, Christopher M. Adams, Richard M. Higashi, David A. Scott, Gang Xin, Zihai Li, Jun Yang, Andrew N. Lane, Teresa Whei-Mei Fan, Ji Zhang, Ruoning Wang

Markey Cancer Center Faculty Publications

Robust and effective T cell immune surveillance and cancer immunotherapy require proper allocation of metabolic resources to sustain energetically costly processes, including growth and cytokine production. Here, we show that asparagine (Asn) restriction on CD8+ T cells exerted opposing effects during activation (early phase) and differentiation (late phase) following T cell activation. Asn restriction suppressed activation and cell cycle entry in the early phase while rapidly engaging the nuclear factor erythroid 2-related factor 2 (NRF2)-dependent stress response, conferring robust proliferation and effector function on CD8+ T cells during differentiation. Mechanistically, NRF2 activation in CD8+ T cells conferred by Asn restriction …


Invited Review: Adrenocortical Function In Avian And Non-Avian Reptiles: Insights From Dispersed Adrenocortical Cells., Rocco V. Carsia, Patrick J. Mcilroy, Henry B John-Alder Jul 2023

Invited Review: Adrenocortical Function In Avian And Non-Avian Reptiles: Insights From Dispersed Adrenocortical Cells., Rocco V. Carsia, Patrick J. Mcilroy, Henry B John-Alder

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Herein we review our work involving dispersed adrenocortical cells from several lizard species: the Eastern Fence Lizard (Sceloporus undulatus), Yarrow's Spiny Lizard (Sceloporus jarrovii), Striped Plateau Lizard (Sceloporus virgatus) and the Yucatán Banded Gecko (Coleonyx elegans). Early work demonstrated changes in steroidogenic function of adrenocortical cells derived from adult S. undulatus associated with seasonal interactions with sex. However, new information suggests that both sexes operate within the same steroidogenic budget over season. The observed sex effect was further explored in orchiectomized and ovariectomized lizards, some supported with exogenous testosterone. Overall, a suppressive effect of testosterone was evident, especially in cells …


A Novel Role For Enos In Regulating Lymphatic Valve Development During Embryogenesis, Drishya Iyer Jun 2023

A Novel Role For Enos In Regulating Lymphatic Valve Development During Embryogenesis, Drishya Iyer

USF Tampa Graduate Theses and Dissertations

Lymphedema is a disease that occurs when lymph flow is impaired, resulting in tissue swelling, fibrosis, chronic inflammation and recurrent secondary infections. Lymphatic valves play a critical role in maintaining unidirectional lymph flow and evidence for valve defects have been reported in lymphedema patients. The lack of drugs that can correct lymphatic valve defects warrants a better understanding of the molecular regulators of lymphatic valve development and maintenance. Lymphatic valves first develop during embryogenesis in response to mechanotransduction signaling pathways triggered by oscillatory lymph flow. Since eNOS (gene name: Nos3) is a well characterized mechanotransduction signaling molecule in blood vessels, …


Role Of Chronic Stress-Induced Neuroinflammation In Rodent Locus Coeruleus Physiology And Anxiety-Like Behaviors, Arthur Anthony Alfonso Reyes Jun 2023

Role Of Chronic Stress-Induced Neuroinflammation In Rodent Locus Coeruleus Physiology And Anxiety-Like Behaviors, Arthur Anthony Alfonso Reyes

Graduate School of Biomedical Sciences Theses and Dissertations

The locus coeruleus (LC), the primary site of brain norepinephrine (NE), is a key anatomical brain region implicated in the stress response. Stress is a neuroendocrine physiologic response to a stressor that promotes organism survival through adaptive change and restoration of homeostasis. The central stress response, which drives behavioral and physiological change, is primarily mediated by activating the hypothalamic-pituitary-adrenal (HPA) axis. While advantageous in the short term, chronic stress exposure can lead to HPA axis and LC dysregulation, which are thought to contribute to the etiology of anxiety disorders. Previous studies demonstrate the effects of acute stress in increasing LC …


Does Vdac2 Have A Bh3 Domain?, Lillian Ferkany May 2023

Does Vdac2 Have A Bh3 Domain?, Lillian Ferkany

Honors Theses

Mitochondrial outer membrane permeabilization (MOMP) by Bax oligomerization triggers apoptosis. BCl-2 family proteins, classified as BH3 only proteins, pro-survival proteins, or pro-apoptotic proteins, control apoptosis partly through their agonist or antagonistic effects on Bax, which are mediated by their conserved BH3 domains. All BH3 domains form an alpha helix containing 5-7 conserved hydrophobic residues, designated H0-H5, and one conserved aspartic acid that drive interaction with Bax and other ‘multi-domain’ BCl-2 members. BH3 agonists induce Bax oligomerization, while BH3 antagonists sequester Bax to prevent MOMP. We discovered that voltage dependent anion channels (VDACs) in the MOM contain a putative BH3-like domain …


Review Of Biomedical Applications Of Cardiovascular Tissue Engineering, Natalie M. Howard May 2023

Review Of Biomedical Applications Of Cardiovascular Tissue Engineering, Natalie M. Howard

Honors College Theses

Tissue engineering can be defined as processes that aim to generate three-dimensional functional tissues in vitrothat have been favorably altered according to the structural, biochemical, electrophysiological, and biomechanical properties of the desired tissue before implantation into the human body. In relation to cardiac tissues, these properties would include the ability to conduct action potentials, withstand systolic pressure, permit sufficient O2 and CO2penetration, sufficient vascularization to supply nutrients for cellular activity, surface topology that enables cellular communication, and more. As heart diseases and instances of myocardial infarction continue to rise worldwide, there is an increasing need for …


Validating A New In Vivo Model To Study Als, Izabela J. Cimachowska May 2023

Validating A New In Vivo Model To Study Als, Izabela J. Cimachowska

Student Theses and Dissertations

Buildup of oxidative stress and mitochondrial dysfunction are well known characteristics of both sporadic and hereditary amyotrophic lateral sclerosis (ALS). While both forms of the disease seem to arise from common cellular dysfunction, the genetic disease is studied to a much greater extent. Engineering novel animal models of the sporadic form of the disease is crucial for development of druggable targets to treat ALS and understand the underlying mechanisms. Interestingly, accumulation of oxidative stress by exacerbated emission of reactive oxygen species (ROS) from presynaptic mitochondria is a hallmark of both hereditary and sporadic ALS. Previous work by our laboratory showed …


Serum Amyloid A Augments The Atherogenic Effects Of Cholesteryl Ester Transfer Protein, Ailing Ji, Andrea C. Trumbauer, Victoria P. Noffsinger, Frederick C. De Beer, Nancy R. Webb, Lisa R. Tannock, Preetha Shridas May 2023

Serum Amyloid A Augments The Atherogenic Effects Of Cholesteryl Ester Transfer Protein, Ailing Ji, Andrea C. Trumbauer, Victoria P. Noffsinger, Frederick C. De Beer, Nancy R. Webb, Lisa R. Tannock, Preetha Shridas

Saha Cardiovascular Research Center Faculty Publications

Serum amyloid A (SAA) is predictive of CVD in humans and causes atherosclerosis in mice. SAA has many proatherogenic effects in vitro. However, HDL, the major carrier of SAA in the circulation, masks these effects. The remodeling of HDL by cholesteryl ester transfer protein (CETP) liberates SAA restoring its proinflammatory activity. Here, we investigated whether deficiency of SAA suppresses the previously described proatherogenic effect of CETP. ApoE¡/¡ mice and apoE¡/¡ mice deficient in the three acute-phase isoforms of SAA (SAA1.1, SAA2.1, and SAA3; “apoE¡/¡ SAA-TKO”) with and without adeno-associated virus-mediated expression of CETP were studied. There was no effect of …


Adipocytes And Innate Immunity In Systemic Sclerosis, Nancy Wareing May 2023

Adipocytes And Innate Immunity In Systemic Sclerosis, Nancy Wareing

Dissertations and Theses (Open Access)

Systemic sclerosis (SSc; scleroderma) is a chronic systemic autoimmune and connective tissue disorder characterized by vasculopathy, autoimmune phenomena, and widespread fibrosis. Skin thickening and tightening is the cardinal feature of SSc and is responsible, in part, for the considerable morbidity of this disease. There are currently no targeted treatments for skin manifestations in SSc, primarily due to our fragmented understanding of its pathophysiologic mechanisms. In PART I, we report a previously unappreciated link between aberrant expression of the developmental gene sine oculis homeobox homolog 1 (SIX1) in skin-associated adipocytes in SSc skin and the early loss of dermal white adipose …


Med13 Degradation Defines A New Receptor-Mediated Autophagy Pathway Activated By Nutrient Deprivation, Sara E. Hanley Apr 2023

Med13 Degradation Defines A New Receptor-Mediated Autophagy Pathway Activated By Nutrient Deprivation, Sara E. Hanley

Graduate School of Biomedical Sciences Theses and Dissertations

Cells are exposed to an enormous amount of diverse extracellular cues but have a limited arsenal of weapons for protecting and maintaining homeostasis. To overcome these restrictions, nature has engineered proteins that have multiple functions. The pleiotropy of using one protein to carry out a variety of functions allows cells to rapidly execute tailored responses to a diverse set of signals. The Cdk8 kinase module (CKM) is a conserved detachable unit of the Mediator complex predominantly known for its role in transcriptional regulation. The CKM is composed of four proteins, the scaffolding proteins Med13 and Med12, as well as the …


The Possible Role For Basigin Receptor Function In The Induction Of Matrix Metalloproteinase Expression In Human Endometrial Stromal Cells, Amy Abel Apr 2023

The Possible Role For Basigin Receptor Function In The Induction Of Matrix Metalloproteinase Expression In Human Endometrial Stromal Cells, Amy Abel

All NMU Master's Theses

10-15% of couples worldwide are affected by infertility. The leading cause of infertility is implantation failure. Molecular communication in precise time and space between an implanting embryo and a receptive uterus is essential for successful implantation. Basigin has been shown to have vital functions within the implantation process. Basigin is best known for inducing the expression of matrix metalloproteinases. Basigin has been shown to induce MMP expression in vitro in human endometrial stromal cell lines (HESC). Understanding how basigin induces matrix metalloproteinases within normal cellular conditions will help researchers understand how these signaling cascades flow in the framework of implantation. …


Thymic Stromal Lymphopoietin Participates In The Host Response To Intra-Amniotic Inflammation Leading To Preterm Labor And Birth, Tomi Kanninen, Li Tao, Roberto Romero, Yi Xu, Marcia Arenas-Hernandez, Jose Galaz, Zhenjie Liu, Derek Miller, Dustyn Levenson, Jonathan M. Greenberg, Jonathan Panzer, Justin Padron, Kevin Theis, Nardhy Gomez-Lopez Phd Mar 2023

Thymic Stromal Lymphopoietin Participates In The Host Response To Intra-Amniotic Inflammation Leading To Preterm Labor And Birth, Tomi Kanninen, Li Tao, Roberto Romero, Yi Xu, Marcia Arenas-Hernandez, Jose Galaz, Zhenjie Liu, Derek Miller, Dustyn Levenson, Jonathan M. Greenberg, Jonathan Panzer, Justin Padron, Kevin Theis, Nardhy Gomez-Lopez Phd

Medical Student Research Symposium

Objective: To determine if bacteria (Ureaplasma parvum and Sneathia spp.) associated with intra-amniotic infection can trigger the induction of cytokine Thymic stromal lymphopoietin (TSLP) in human amnion epithelial cells (hAECs) in vitro.

Material or subjects: Amniotic fluid and chorioamniotic membrane (CAM) were collected from women with sPTL who delivered at term (n=30) or preterm without intra-amniotic inflammation (n=34), with sterile intra-amniotic inflammation (SIAI, n=27), or with intra-amniotic infection (IAI, n=17). Amnion epithelial cells (AECs), Ureaplasma parvum, and Sneathia spp. were also utilized.

Methods: The expression of TSLP, TSLPR, and IL-7Rα was evaluated in amniotic fluid or CAM by …


Impact Of The Dimethyl Sulfoxide Reductase Superfamily On The Evolution Of Biogeochemical Cycles, Michael Wells, Minjae Kim, Denise M. Akob, Partha Basu, John F. Stolz Mar 2023

Impact Of The Dimethyl Sulfoxide Reductase Superfamily On The Evolution Of Biogeochemical Cycles, Michael Wells, Minjae Kim, Denise M. Akob, Partha Basu, John F. Stolz

UK CARES Faculty Publications

The dimethyl sulfoxide reductase (or MopB) family is a diverse assemblage of enzymes found throughout Bacteria and Archaea. Many of these enzymes are believed to have been present in the last universal common ancestor (LUCA) of all cellular lineages. However, gaps in knowledge remain about how MopB enzymes evolved and how this diversification of functions impacted global biogeochemical cycles through geologic time. In this study, we perform maximum likelihood phylogenetic analyses on manually curated comparative genomic and metagenomic data sets containing over 47,000 distinct MopB homologs. We demonstrate that these enzymes constitute a catalytically and mechanistically diverse superfamily defined not …


Loss Of Peroxiredoxin Iv Protects Mice From Azoxymethane/Dextran Sulfate Sodium-Induced Colorectal Cancer Development, Pratik Thapa, Hong Jiang, Na Ding, Yanning Hao, Aziza Alshahrani, Eun Young Lee, Junichi Fujii, Qiou Wei Mar 2023

Loss Of Peroxiredoxin Iv Protects Mice From Azoxymethane/Dextran Sulfate Sodium-Induced Colorectal Cancer Development, Pratik Thapa, Hong Jiang, Na Ding, Yanning Hao, Aziza Alshahrani, Eun Young Lee, Junichi Fujii, Qiou Wei

Markey Cancer Center Faculty Publications

Peroxiredoxin IV (Prx4), a typical two-cysteine-containing member of the peroxidase family, functions as an antioxidant to maintain cellular redox homeostasis through the reduction of reactive oxygen species (ROS) via cycles of oxidation–reduction reactions. Under oxidative stress, all Prxs including Prx4 are inactivated as their catalytic cysteines undergo hyperoxidation, and hyperoxidized two-cysteine Prxs can be exclusively repaired and revitalized through the reduction cycle catalyzed by sulfiredoxin (Srx). Previously, we showed that Prx4 is a preferred substrate of Srx, and knockout of Srx in mice leads to resistance to azoxymethane/dextran sulfate sodium (AOM/DSS)-induced colon carcinogenesis. To further understand the significance of the …


Critical Role Of The Sulfiredoxin-Peroxiredoxin Iv Axis In Urethane-Induced Non-Small Cell Lung Cancer, Yanning Hao, Hong Jiang, Pratik Thapa, Na Ding, Aziza Alshahrani, Junichi Fujii, Michel B. Toledano, Qiou Wei Feb 2023

Critical Role Of The Sulfiredoxin-Peroxiredoxin Iv Axis In Urethane-Induced Non-Small Cell Lung Cancer, Yanning Hao, Hong Jiang, Pratik Thapa, Na Ding, Aziza Alshahrani, Junichi Fujii, Michel B. Toledano, Qiou Wei

Markey Cancer Center Faculty Publications

Non-small cell lung cancer (NSCLC), the most common type of lung cancer, etiologically associates with tobacco smoking which mechanistically contributes to oxidative stress to facilitate the occurrence of mutations, oncogenic transformation and aberrantly activated signaling pathways. Our previous reports suggested an essential role of Sulfiredoxin (Srx) in promoting the development of lung cancer in humans, and was causally related to Peroxiredoxin IV (Prx4), the major downstream substrate and mediator of Srx-enhanced signaling. To further explore the role of the Srx-Prx4 axis in de novo lung tumorigenesis, we established Prx4−/− and Srx−/−/Prx4−/− mice in pure FVB/N background. Together with wild-type litter …


Apobec3 Regulation By Thyroid Hormone, Michelle Santiago Jan 2023

Apobec3 Regulation By Thyroid Hormone, Michelle Santiago

All Graduate Theses, Dissertations, and Other Capstone Projects

Thyroid hormone (TH) is crucial for many biological processes, including the development of the auditory system. Appropriate thyroid hormone signaling is important for the development of the cochlea, leading to the successful onset of hearing. More specifically, TH influences the timing of remodeling of the greater epithelial ridge (GER), a transient cochlear structure that secretes proteins that contribute to the formation of the tectorial membrane. Developmental hypothyroidism results in delayed GER regression, whereas excess TH results in premature remodeling. Both conditions result in deafness. However, it is unknown how TH mediates GER remodeling. Expression profiling identified APOBEC3 (A3) as a …


Best3-Mediated Mekk2/3 Activation: A Novel Therapeutic Target In Aortopathies, Tatiana Zyrianova, Benjamin Lopez, Kathlyn Zou, Charles Gu, Dayna Pham, Sriharsha Talapaneni, Christopher M. Waters, Riccardo Olcese, Andreas Schwingshackl Jan 2023

Best3-Mediated Mekk2/3 Activation: A Novel Therapeutic Target In Aortopathies, Tatiana Zyrianova, Benjamin Lopez, Kathlyn Zou, Charles Gu, Dayna Pham, Sriharsha Talapaneni, Christopher M. Waters, Riccardo Olcese, Andreas Schwingshackl

Saha Cardiovascular Research Center Faculty Publications

Influenza-A virus (IAV) infects yearly an estimated one billion people worldwide, resulting in 300,000–650,000 deaths. Preventive vaccination programs and antiviral medications represent the mainstay of therapy, but with unacceptably high morbidity and mortality rates, new targeted therapeutic approaches are urgently needed. Since inflammatory processes are commonly associated with measurable changes in the cell membrane potential (Em), we investigated whether Em hyperpolarization via TREK-1 (K2P 2.1) K þ channel activation can protect against influenza-A virus (IAV)-induced pneumonia. We infected mice with IAV, which after 5 days caused 10–15% weight loss and a decrease in spontaneous activity, representing a clinically relevant infection. …


Characterizing Cellular Injury And Inflammation With Aldob-/-Mouse Model Of Mafld, Andy Rashid Jan 2023

Characterizing Cellular Injury And Inflammation With Aldob-/-Mouse Model Of Mafld, Andy Rashid

All Master's Theses

Metabolic-associated fatty liver disease (MAFLD) affects 1 in 3 people in the US and is a healthcare burden on the order of billions of dollars. MAFLD is characterized by pathological lipid accumulation in the liver, excess production of triglycerides and cholesterol, and export of LDL particles that raise serum lipid levels. These metabolic perturbations can lead to the development of liver fibrosis, chronic inflammation, and insulin resistance. Diagnosing MAFLD prior to fibrosis is crucial for successful intervention and prevention of advanced liver disease and other metabolic complications. Fructose-1Phospahte (F1P) accumulation from fructose overconsumption can drive hepatic lipogenesis and MAFLD progression. …


The Effects Of Sex On Zebrafish Bone Metabolism, Simon Bagatto Jan 2023

The Effects Of Sex On Zebrafish Bone Metabolism, Simon Bagatto

Williams Honors College, Honors Research Projects

I investigated the effects of diet and sex on zebrafish bone metabolism. Zebrafish were subjected to either a high-calorie or low-calorie diet over a five-week period. After this diet, zebrafish scales were used to measure alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP) enzyme activity with a fluorescent substrate. The enzyme activities were markers of the osteoblasts (ALP) and the osteoclasts (TRAP). These data were compared among sex and diet of the zebrafish using a repeated measures ANOVA statistical test. I also measured the number of resorption lacunae per scale (another indicator of osteoclast activity). The results showed higher TRAP …


Dimerization Of Dopamine (D2) And Adenosine (A2a) Receptors, Elena Vukovic, Jackson M. Macatol Jan 2023

Dimerization Of Dopamine (D2) And Adenosine (A2a) Receptors, Elena Vukovic, Jackson M. Macatol

Williams Honors College, Honors Research Projects

This experiment will aim to explore the heterodimerization of Dopamine (D2) and Adenosine (A2A) receptors in cells when bound to different ligands. Borroto-Escuela et al. (2018) investigated the dimerization of the A2AR-D2R in rats when administered with cocaine, and they found that disrupting the A2AR-D2R complex restores the cocaine reward system in rats. This was a strong influence as to why we chose to investigate A2AR-D2R dimerization in Chinese hamster ovary (CHO) cells.

One goal that we have for this experiment is to combine our current laboratory skills with new laboratory techniques. There are constantly new techniques in labs, and …


Bilirubin Levels Are Negatively Correlated With Adiposity In Obese Men And Women, And Its Catabolized Product, Urobilin, Is Positively Associated With Insulin Resistance, Zachary A. Kipp, Mei Xu, Evelyn A. Bates, Wang-Hsin Lee, Philip A. Kern, Terry D. Hinds Jr. Jan 2023

Bilirubin Levels Are Negatively Correlated With Adiposity In Obese Men And Women, And Its Catabolized Product, Urobilin, Is Positively Associated With Insulin Resistance, Zachary A. Kipp, Mei Xu, Evelyn A. Bates, Wang-Hsin Lee, Philip A. Kern, Terry D. Hinds Jr.

Markey Cancer Center Faculty Publications

Bilirubin levels in obese humans and rodents have been shown to be lower than in their lean counterparts. Some studies have proposed that the glucuronyl UGT1A1 enzyme that clears bilirubin from the blood increases in the liver with obesity. UGT1A1 clearance of bilirubin allows more conjugated bilirubin to enter the intestine, where it is catabolized into urobilin, which can be then absorbed via the hepatic portal vein. We hypothesized that when bilirubin levels are decreased, the urobilin increases in the plasma of obese humans, as compared to lean humans. To test this, we measured plasma levels of bilirubin and urobilin, …


Sex-Dependent Effects Of Induced Acute Inflammation On Glucose Homeostasis And Rna Editing Enzymes, Christian A. Rivas Jan 2023

Sex-Dependent Effects Of Induced Acute Inflammation On Glucose Homeostasis And Rna Editing Enzymes, Christian A. Rivas

Graduate Theses/Dissertations

The first line of defense against bodily insults, like pathogen invasion, is the innate immune system. Innate immunity sets in motion countless cascades that result in inflammation. Inflammation simultaneously affects multiple biological processes like metabolism and gene expression. Males and females react differently to inflammation. To understand both molecular and physiological sex differences in inflammation, we examined how inflammation affects gene expression and glucose metabolism. Adenosine deaminase acting on RNA (ADAR1) is upregulated by inflammation and catalyzes RNA editing, a process where nucleotides encoded by the genome are modified. ADAR1 also controls the innate immune reaction by decreasing activity of …


Elucidation Of The Role Of Agouti-Signaling Protein Throughout Folliculogenesis And Early Embryonic Development In Cattle, Heather L. Chaney Jan 2023

Elucidation Of The Role Of Agouti-Signaling Protein Throughout Folliculogenesis And Early Embryonic Development In Cattle, Heather L. Chaney

Graduate Theses, Dissertations, and Problem Reports (ETD)

The oocyte expresses certain genes during folliculogenesis to regulate the acquisition of oocyte competence. Oocyte competence, which refers to the presence of imperative molecular factors in the oocyte that are critical for high oocyte quality, is directly related to the ability of the oocyte to result in a successful pregnancy following fertilization. Over the past few decades, the development and optimization of assisted reproductive technologies, particularly in vitrofertilization, have enabled the beef and dairy industries to advance cattle genetics and productivity. However, only approximately 40% of bovine embryos will develop to the blastocyst stage in vitro. In addition, bovine embryos …


The Investigation Of Novel Bovine Oocyte-Specific Long Non-Coding Rnas And Their Roles In Oocyte Maturation And Early Embryonic Development, Jaelyn Zoe Current Jan 2023

The Investigation Of Novel Bovine Oocyte-Specific Long Non-Coding Rnas And Their Roles In Oocyte Maturation And Early Embryonic Development, Jaelyn Zoe Current

Graduate Theses, Dissertations, and Problem Reports (ETD)

Early embryonic loss is a significant factor in livestock species' infertility, resulting in an economic deficit. In cattle, the in vivo fertilization rate is ~90%, with an average calving rate of about 55%, indicating an embryonic-fetal mortality rate of roughly 35%. Further, 70-80% of total embryonic loss in cattle occurs during the first three weeks after insemination, particularly between days 7-16. Growing evidence indicates that the oocyte plays an active role in regulating critical aspects of the reproductive process required for successful fertilization, embryo development, and pregnancy. However, defining oocyte quality remains enigmatic. Recently, many have abandoned the notion that …


Underlying Mechanism Of Ovarian Reserve Preservation From Gonadotoxicity, Yi Luan Dec 2022

Underlying Mechanism Of Ovarian Reserve Preservation From Gonadotoxicity, Yi Luan

Theses & Dissertations

Cancer therapies often lead to premature ovarian insufficiency by ovarian damage and follicle depletion. However, the oocyte death pathway induced by chemotherapies has been debated. Here we clarified the precise mechanism of ovarian depletion induced by cyclophosphamide and doxorubicin. Cyclophosphamide induced direct apoptosis in oocytes rather than overactivation of primordial follicles. Dormant oocytes instead of activated oocytes with high PI3K activity were more sensitive to cyclophosphamide. Although the ABL inhibitor, GNF2, has been proposed to ameliorate the apoptosis of primordial follicles against cyclophosphamide, GNF2 did not prevent the loss of primordial follicles induced by cyclophosphamide in the systems tested. Oocyte-specific …


Establishing The Efficacy Of Non-Cellular Components Of Adipose-Derived Stromal Vascular Fraction In Promoting Angiogenesis., Daniel Benson Dec 2022

Establishing The Efficacy Of Non-Cellular Components Of Adipose-Derived Stromal Vascular Fraction In Promoting Angiogenesis., Daniel Benson

Electronic Theses and Dissertations

Microvascular disease is hallmarked by pathophysiological conditions such as endothelial senescence, intimal thickening which impairs vasodilation, and regression of the capillary beds causing tissue ischemia in the myocardium or in peripheral vascular networks. Adipose-derived stromal vascular fraction (SVF) has previously demonstrated the ability to revascularize tissue. Increasing evidence shows that regenerative cells elicit their therapeutic benefit by paracrine mechanisms, leaving open extracellular vesicles (EVs) as a potential crux of the cell therapy paradigm. To test this idea, three types of gelatin methacrylate hydrogels were employed: SVF gels, EV gels derived from SVF, and blank control gels, which were used in-vitro …


Effect Of Umbilical Cord Essential And Toxic Elements, Thyroid Levels, And Vitamin D On Childhood Development, Jesse Cottrell, Chelsea Nelson, Catherine Waldron, Mackenzie Bergeron, Abigail Samson, Monica Valentovic Dec 2022

Effect Of Umbilical Cord Essential And Toxic Elements, Thyroid Levels, And Vitamin D On Childhood Development, Jesse Cottrell, Chelsea Nelson, Catherine Waldron, Mackenzie Bergeron, Abigail Samson, Monica Valentovic

Biomedical Sciences

Introduction: The in-utero environment has dramatic effects on childhood development. We hypothesized prenatal levels of inorganic agents, thyroid levels, and Vitamin D effect childhood development.

Methods: Umbilical cord blood was collected from April 3, 2013 to January 30, 2014 and analyzed for 20 different elements, thyroid and Vitamin D. A retrospective review (n = 60) was performed of well-child examinations from birth to 5 years old (y.o.).

Results: There were associations with calcium and 4 month BMI (p = <0.01), 12 month language (p = 0.03); Magnesium and 6 month language (p = 0.04) and gross motor skills at 5 years old (y.o.) (p = 0.03); Copper and 12 month fine motor (p = 0.02); Zinc with fine motor (p = <0.01) and language (p = 0.03) at 2 y.o.; Manganese was associated with language development at 2 y.o. (p = 0.02); Molybdenum and fine motor at 12 months of age (p = 0.02); Selenium with gross motor (p = 0.04) and BMI (p = 0.02) at 5 y.o.; Lead with cognitive function at 4 months (p = 0.04) and 2 y.o. (p = 0.01); Mercury with gross motor at 4 months (p = 0.04) and language at 2 y.o. (p = 0.02). Platinum at 12 months of age (p = <.01) as well as multiple associations at 5 y.o. (p = <.01). Thyroid function tests for free T3 were associated with multiple cognitive and physical milestones. T3 Uptake was associated with 5 y.o. gross motor skills (p = 0.02). Total and Free T4 was associated with cognitive development (p = <.01) and fine motor development, respectively. Vitamin D was associated with a delay of fine motor development (p<0.01).

Conclusion: There were multiple associations between umbilical cord essential and toxic elements, thyroid levels, and Vitamin D on childhood development.