Digital Commons Network^™

Mapk4 Promotes Prostate Cancer By Concerted Activation Of Androgen Receptor And Akt, Tao Shen, Wei Wang, Wolong Zhou, Ilsa Coleman, Qinbo Cai, Bingning Dong, Michael M Ittmann, Chad J Creighton, Yingnan Bian, Yanling Meng, David R Rowley, Peter S Nelson, David D Moore, Feng Yang

Faculty, Staff and Students Publications

Prostate cancer (PCa) is the second leading cause of cancer death in American men. Androgen receptor (AR) signaling is essential for PCa cell growth/survival and remains a key therapeutic target for lethal castration-resistant PCa (CRPC). GATA2 is a pioneer transcription factor crucial for inducing AR expression/activation. We recently reported that MAPK4, an atypical MAPK, promotes tumor progression via noncanonical activation of AKT. Here, we demonstrated that MAPK4 activated AR by enhancing GATA2 transcriptional expression and stabilizing GATA2 protein through repression of GATA2 ubiquitination/degradation. MAPK4 expression correlated with AR activation in human CRPC. Concerted activation of both GATA2/AR and AKT by …

The Rac-Gef Tiam1 Promotes Dendrite And Synapse Stabilization Of Dentate Granule Cells And Restricts Hippocampal-Dependent Memory Functions, Jinxuan Cheng, Federico Scala, Francisco A Blanco, Sanyong Niu, Karen Firozi, Laura Keehan, Shalaka Mulherkar, Emmanouil Froudarakis, Lingyong Li, Joseph G Duman, Xiaolong Jiang, Kimberley F Tolias

Faculty, Staff and Students Publications

The dentate gyrus (DG) controls information flow into the hippocampus and is critical for learning, memory, pattern separation, and spatial coding, while DG dysfunction is associated with neuropsychiatric disorders. Despite its importance, the molecular mechanisms regulating DG neural circuit assembly and function remain unclear. Here, we identify the Rac-GEF Tiam1 as an important regulator of DG development and associated memory processes. In the hippocampus, Tiam1 is predominantly expressed in the DG throughout life. Global deletion of Tiam1 in male mice results in DG granule cells with simplified dendritic arbors, reduced dendritic spine density, and diminished excitatory synaptic transmission. Notably, DG …

Phenytoin Inhibits Cell Proliferation Through Microrna-196a-5p In Mouse Lip Mesenchymal Cells, Hiroki Yoshioka, Sai Shankar Ramakrishnan, Akiko Suzuki, Junichi Iwata

Faculty, Staff and Student Publications

Cleft lip (CL) is one of the most common birth defects. It is caused by either genetic mutations or environmental factors. Recent studies suggest that environmental factors influence the expression of noncoding RNAs [e.g., microRNA (miRNA)], which can regulate the expression of genes crucial for cellular functions. In this study, we examined which miRNAs are associated with CL. Among 10 candidate miRNAs (miR-98-3p, miR-101a-3p, miR-101b-3p, miR-141-3p, miR-144-3p, miR-181a-5p, miR-196a-5p, miR-196b-5p, miR-200a-3p, and miR-710) identified through our bioinformatic analysis of CL-associated genes, overexpression of miR-181a-5p, miR-196a-5p, miR-196b-5p, and miR-710 inhibited cell proliferation through suppression of genes associated with CL in cultured …

Vertical Sleeve Gastrectomy Confers Metabolic Improvements By Reducing Intestinal Bile Acids And Lipid Absorption In Mice, Lili Ding, Eryun Zhang, Qiaoling Yang, Lihua Jin, Kyle M Sousa, Bingning Dong, Yangmeng Wang, Jui Tu, Xiaoxiao Ma, Jingyan Tian, Hongli Zhang, Zhipeng Fang, Ana Guan, Yixin Zhang, Zhengtao Wang, David D Moore, Li Yang, Wendong Huang

Faculty, Staff and Students Publications

Vertical sleeve gastrectomy (VSG) is a highly effective bariatric surgery that sustainably treats obesity and type 2 diabetes (T2D). However, the underlying mechanisms governing its metabolic benefits remain unclear. In this study, we have used four different genetically modified mouse lines to understand the link between bile acid circulation and metabolic effects of VSG. Instead of directly activating the nuclear bile acid receptor farnesoid X receptor (Fxr) in the liver or intestine, VSG reduces intestinal levels of bile acids, thereby decreasing fat absorption in the intestine. Given the rising popularity of bariatric surgeries to treat obesity and associated T2D, the …

Hermansky-Pudlak Syndrome-2 Alters Mitochondrial Homeostasis In The Alveolar Epithelium Of The Lung, Karina Cuevas-Mora, Willy Roque, Hoora Shaghaghi, Bernadette R Gochuico, Ivan O Rosas, Ross Summer, Freddy Romero

Faculty, Staff and Students Publications

BACKGROUND: Mitochondrial dysfunction has emerged as an important player in the pathogenesis of idiopathic pulmonary fibrosis (IPF), a common cause of idiopathic interstitial lung disease in adults. Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder that causes a similar type of pulmonary fibrosis in younger adults, although the role of mitochondrial dysfunction in this condition is not understood.

METHODS: We performed a detailed characterization of mitochondrial structure and function in lung tissues and alveolar epithelial cells deficient in the adaptor protein complex 3 beta 1 (Ap3b1) subunit, the gene responsible for causing subtype 2 of HPS (HPS-2).

RESULTS: We …

Eosinophils Attenuate Hepatic Ischemia-Reperfusion Injury In Mice Through St2-Dependent Il-13 Production, Yaochun Wang, Yang Yang, Meng Wang, Shuhong Wang, Jong-Min Jeong, Long Xu, Yankai Wen, Christoph Emontzpohl, Constance Lynn Atkins, Kevin Duong, Nicolas F Moreno, Xiaoyi Yuan, David R Hall, Wasim Dar, Dechun Feng, Bin Gao, Yong Xu, Zoltan Czigany, Sean P Colgan, J Steve Bynon, Shizuo Akira, Jared M Brown, Holger K Eltzschig, Elizabeth A Jacobsen, Cynthia Ju

Faculty, Staff and Students Publications

Eosinophils are a myeloid cell subpopulation that mediates type 2 T helper cell immune responses. Unexpectedly, we identified a rapid accumulation of eosinophils in 22 human liver grafts after hepatic transplantation. In contrast, no eosinophils were detectable in healthy liver tissues before transplantation. Studies with two genetic mouse models of eosinophil deficiency and a mouse model of antibody-mediated eosinophil depletion revealed exacerbated liver injury after hepatic ischemia and reperfusion. Adoptive transfer of bone marrow-derived eosinophils normalized liver injury of eosinophil-deficient mice and reduced hepatic ischemia and reperfusion injury in wild-type mice. Mechanistic studies combining genetic and adoptive transfer approaches identified …

Lkb1 And Ampk Instruct Cone Nuclear Position To Modify Visual Function, Courtney A Burger, Nicholas E Albrecht, Danye Jiang, Justine H Liang, Ross A Poché, Melanie A Samuel

Faculty, Staff and Students Publications

Cone photoreceptors detect light and are responsible for color vision. These cells display a distinct polarized morphology where nuclei are precisely aligned in the apical retina. However, little is known about the mechanisms involved in cone nuclear positioning or the impact of this organization on retina function. We show that the serine/threonine kinase LKB1 and one of its substrates, AMPK, regulate cone nuclear positioning. In the absence of either molecule, cone nuclei are misplaced along the axon, resulting in altered nuclear lamination. LKB1 is required specifically in cones to mediate this process, and disruptions in nuclear alignment result in reduced …

Spliceosome-Targeted Therapies Trigger An Antiviral Immune Response In Triple-Negative Breast Cancer, Elizabeth A Bowling, Jarey H Wang, Fade Gong, William Wu, Nicholas J Neill, Ik Sun Kim, Siddhartha Tyagi, Mayra Orellana, Sarah J Kurley, Rocio Dominguez-Vidaña, Hsiang-Ching Chung, Tiffany Y-T Hsu, Julien Dubrulle, Alexander B Saltzman, Heyuan Li, Jitendra K Meena, Gino M Canlas, Srinivas Chamakuri, Swarnima Singh, Lukas M Simon, Calla M Olson, Lacey E Dobrolecki, Michael T Lewis, Bing Zhang, Ido Golding, Jeffrey M Rosen, Damian W Young, Anna Malovannaya, Fabio Stossi, George Miles, Matthew J Ellis, Lihua Yu, Silvia Buonamici, Charles Y Lin, Kristen L Karlin, Xiang H-F Zhang, Thomas F Westbrook

Faculty, Staff and Students Publications

Many oncogenic insults deregulate RNA splicing, often leading to hypersensitivity of tumors to spliceosome-targeted therapies (STTs). However, the mechanisms by which STTs selectively kill cancers remain largely unknown. Herein, we discover that mis-spliced RNA itself is a molecular trigger for tumor killing through viral mimicry. In MYC-driven triple-negative breast cancer, STTs cause widespread cytoplasmic accumulation of mis-spliced mRNAs, many of which form double-stranded structures. Double-stranded RNA (dsRNA)-binding proteins recognize these endogenous dsRNAs, triggering antiviral signaling and extrinsic apoptosis. In immune-competent models of breast cancer, STTs cause tumor cell-intrinsic antiviral signaling, downstream adaptive immune signaling, and tumor cell death. Furthermore, RNA …

Implications Of Oligomeric Amyloid-Beta (Oaβ42) Signaling Through Α7Β2-Nicotinic Acetylcholine Receptors (Nachrs) On Basal Forebrain Cholinergic Neuronal Intrinsic Excitability And Cognitive Decline, Andrew A George, Jaime M Vieira, Cameron Xavier-Jackson, Michael T Gee, John R Cirrito, Heather A Bimonte-Nelson, Marina R Picciotto, Ronald J Lukas, Paul Whiteaker

2020-Current year OA Pubs

Neuronal and network-level hyperexcitability is commonly associated with increased levels of amyloid-β (Aβ) and contribute to cognitive deficits associated with Alzheimer's disease (AD). However, the mechanistic complexity underlying the selective loss of basal forebrain cholinergic neurons (BFCNs), a well-recognized characteristic of AD, remains poorly understood. In this study, we tested the hypothesis that the oligomeric form of amyloid-β (oAβ

Coxsackievirus B3 Infection Early In Pregnancy Induces Congenital Heart Defects Through Suppression Of Fetal Cardiomyocyte Proliferation, Vipul Sharma, Lisa S Goessling, Anoop K Brar, Chetanchandra S Joshi, Indira U Mysorekar, Pirooz Eghtesady

Open Access Publications

Background Coxsackievirus B (CVB) is the most common cause of viral myocarditis. It targets cardiomyocytes through coxsackie and adenovirus receptor, which is highly expressed in the fetal heart. We hypothesized CVB3 can precipitate congenital heart defects when fetal infection occurs during critical window of gestation. Methods and Results We infected C57Bl/6 pregnant mice with CVB3 during time points in early gestation (embryonic day [E] 5, E7, E9, and E11). We used different viral titers to examine possible dose-response relationship and assessed viral loads in various fetal organs. Provided viral exposure occurred between E7 and E9, we observed characteristic features of …

Comparison Of N- And C-Terminally Endogenously Gfp-Tagged Wee-1.3 Strains In, Lourds M Fernando, Kyrionna Golliday, Ruby Boateng, Anna K Allen

Faculty Research 2021

We have generated a WEE-1.3 strain in C. elegans where we have endogenously tagged the C-terminus with GFP. In this publication we demonstrate that this new strain exhibits the same expression localization pattern as the WEE-1.3 antibody and N-terminally endogenously GFP-tagged WEE-1.3 strain that have been previously published. We also show for the first time that endogenously tagging WEE-1.3 at either termini does not affect the reproductive function of the worms.

Multiwalled Carbon Nanotubes Co-Delivering Sorafenib And Epidermal Growth Factor Receptor Sirna Enhanced Tumor-Suppressing Effect On Liver Cancer., Zhili Wen, Yuliang Feng, Youwen Hu, Lingyan Lian, Hongyan Huang, Li Guo, Shanwen Chen, Qian Yang, Moran Zhang, Lijun Wan, Kedong Xu, Degejirifu, Xiaohua Yan

Faculty Research 2021

OBJECTIVE: This study aimed to investigate the effects of multiwalled carbon nanotubes (MWNTs) co-delivering sorafenib (Sor) and epidermal growth factor receptor (EGFR) siRNA (MWNT/Sor/siRNA) on tumor growth in liver cancer (LC).

RESULTS: MWNT/Sor/siRNA was proved to possess increased Sor release, high siRNA stability, and enhanced cellular uptake. In addition, MWNT treatment has few effects on cell proliferation and apoptosis in HepG2 cells; however, MWNT/Sor/siRNA treatment significantly inhibited clone number and induced cell apoptosis, which shows a more favorable antitumor effect than MWNT/Sor and free Sor and free siRNA in HepG2 cells. Moreover MWNT/Sor/siRNA treatment has the most significant antitumor effect …

The Gene Ontology Resource: Enriching A Gold Mine., Gene Ontology Consortium, Judith A. Blake, Mary E. Dolan, Harold J. Drabkin, David P. Hill

Faculty Research 2021

The Gene Ontology Consortium (GOC) provides the most comprehensive resource currently available for computable knowledge regarding the functions of genes and gene products. Here, we report the advances of the consortium over the past two years. The new GO-CAM annotation framework was notably improved, and we formalized the model with a computational schema to check and validate the rapidly increasing repository of 2838 GO-CAMs. In addition, we describe the impacts of several collaborations to refine GO and report a 10% increase in the number of GO annotations, a 25% increase in annotated gene products, and over 9,400 new scientific articles …

Mouse Genome Database (Mgd): Knowledgebase For Mouse-Human Comparative Biology., Judith A. Blake, Richard M. Baldarelli, James A. Kadin, Joel E Richardson, Cynthia Smith, Carol J Bult, Mouse Genome Database Group

Faculty Research 2021

The Mouse Genome Database (MGD; http://www.informatics.jax.org) is the community model organism knowledgebase for the laboratory mouse, a widely used animal model for comparative studies of the genetic and genomic basis for human health and disease. MGD is the authoritative source for biological reference data related to mouse genes, gene functions, phenotypes and mouse models of human disease. MGD is the primary source for official gene, allele, and mouse strain nomenclature based on the guidelines set by the International Committee on Standardized Nomenclature for Mice. MGD's biocuration scientists curate information from the biomedical literature and from large and small datasets contributed …

The R-Enantiomer Of Ketorolac Reduces Ovarian Cancer Tumor Burden In Vivo, Martha M. Grimes, S Ray Kenney, Dayna R. Dominguez, Kathryn J. Brayer, Yuna Guo, Angela Wandinger-Ness, Laurie G. Hudson

Pathology Research and Scholarship

BACKGROUND: Rho-family GTPases, including Ras-related C3 botulinum toxin substrate 1 (Rac1) and cell division control protein 42 (Cdc42), are important modulators of cancer-relevant cell functions and are viewed as promising therapeutic targets. Based on high-throughput screening and cheminformatics we identified the R-enantiomer of an FDA-approved drug (ketorolac) as an inhibitor of Rac1 and Cdc42. The corresponding S-enantiomer is a non-steroidal anti-inflammatory drug (NSAID) with selective activity against cyclooxygenases. We reported previously that R-ketorolac, but not the S-enantiomer, inhibited Rac1 and Cdc42-dependent downstream signaling, growth factor stimulated actin cytoskeleton rearrangements, cell adhesion, migration and invasion in ovarian cancer cell lines and …

The Effect Of Age On Neurological Inflammation To Acute Sleep Fragmentation In Mice, Molly Taylor

Mahurin Honors College Capstone Experience/Thesis Projects

Obstructive sleep apnea is identified by recurring events of airway collapse during sleep, intermittent hypoxia, and perturbations in sleep continuity, known as sleep fragmentation. There is evidence to suggest that elderly patients are more at risk of developing obstructive sleep apnea. The purpose of this study was to assess whether age affects neurological inflammatory responses to acute sleep fragmentation. This assessment was made by subjecting young (4-5 months old) and old (10-11 months old) male C57BL/6j mice to automated sleep fragmentation, as well as having mice in both age categories as a control with no sleep fragmentation, for twenty-four hours. …

Ionizable Lipid Nanoparticles For In Utero Mrna Delivery., Rachel S. Riley, Meghana V Kashyap, Margaret M Billingsley, Brandon White, Mohamad-Gabriel Alameh, Sourav K Bose, Philip W Zoltick, Hiaying Li, Rui Zhang, Andrew Y Cheng, Drew Weissman, William H Peranteau, Michael J Mitchell

Henry M. Rowan College of Engineering Departmental Research

Clinical advances enable the prenatal diagnosis of genetic diseases that are candidates for gene and enzyme therapies such as messenger RNA (mRNA)-mediated protein replacement. Prenatal mRNA therapies can treat disease before the onset of irreversible pathology with high therapeutic efficacy and safety due to the small fetal size, immature immune system, and abundance of progenitor cells. However, the development of nonviral platforms for prenatal delivery is nascent. We developed a library of ionizable lipid nanoparticles (LNPs) for in utero mRNA delivery to mouse fetuses. We screened LNPs for luciferase mRNA delivery and identified formulations that accumulate within fetal livers, lungs, …

Inhibiting Fatty Acid Binding Protein Family Members Decreases Multiple Myeloma Cell Proliferation Through Effecting The Myc Pathway, Mariah Farrell, Heather Fairfield, Anastasia D'Amico, Carolyne Falank, Connor Murphy, Michaela Reagan

Costas T. Lambrew Research Retreat 2021

FABP inhibition leads to increased survival of myeloma bearing mice and decreased cell growth by inhibiting MYC signaling.

Uncovering The ‘Hidden Fibrosis’ Of Pediatric Congenital Aortic Valve Stenosis Via Targeted Mass Spectrometry Approaches, Cassandra Lucille Clift

MUSC Theses and Dissertations

Congenital aortic valve stenosis (CAVS) affects up to 10% of the world population without medical therapies to treat the disease. New molecular targets are continually being sought that can halt CAVS progression, particularly in pediatric patients where bioengineered solutions are not ideal. Collagen deregulation is a hallmark of pediatric CAVS yet remains mostly undefined. Here, histological studies were paired with high resolution accurate mass (HRAM) collagen-targeting proteomics and imaging mass spectrometry to investigate collagen fiber production with localized collagen regulation associated with human AV development and pediatric end-stage CAVS (pCAVS). Histological studies identified collagen fiber realignment and unique regions of …

Obesity And The Hippocampus: How Diet-Induced Insulin Resistance Contributes To Memory Impairment, Luke S. Watson

MUSC Theses and Dissertations

Over 93 million Americans are obese, a condition which also increases the risk for developing neurocognitive disorders such as Alzheimer’s disease. Insulin is critically important for maintaining homeostasis in the central nervous system, but in order to play this role it has to be transported in from the periphery. Interestingly, peripheral hyperinsulinemia is linked to reduced central nervous system insulin. The overarching hypothesis of this dissertation is that chronic hyperinsulinemia reduces hippocampal insulin transport, thereby dysregulating insulin receptor signaling proteins and leading to memory impairment. In order to test this hypothesis, we assessed the high-fat diet mouse model in two …

Dietary Phytoestrogens Ameliorate Hydrochloric Acid-Induced Chronic Lung Injury And Pulmonary Fibrosis In Mice, Pavel Solopov, Ruben Manuel Luciano Colunga Biancatelli, Christiana Dimitropoulou, John D. Catravas

Bioelectrics Publications

We previously reported that female mice exhibit protection against chemically induced pulmonary fibrosis and suggested a potential role of estrogen. Phytoestrogens act, at least in part, via stimulation of estrogen receptors; furthermore, compared to residents of Western countries, residents of East Asian countries consume higher amounts of phytoestrogens and exhibit lower rates of pulmonary fibrosis. Therefore, we tested the hypothesis that dietary phytoestrogens ameliorate the severity of experimentally induced pulmonary fibrosis. Male mice placed on either regular soybean diet or phytoestrogen-free diet were instilled with 0.1 N HCl to provoke pulmonary fibrosis. Thirty days later, lung mechanics were measured as …

Opioid System's Involvement In Ketamine's Antidepressant-Like Effects, Fan Zhang

Theses and Dissertations

Depression is one of the most debilitating disorders in the world. The currently available medications typically have a 2-4 week delay in their therapeutic effects and are ineffective for about 40% of patients. In 2000, a subanesthetic dose (0.5 mg/kg i.e.) of the dissociative anesthetic ketamine was reported to have both rapid and robust antidepressant effects in in treatment-resistant depressed patients. However, the mechanisms responsible for ketamine’s antidepressant effects remain unclear. In 2018, a clinical study reported that pretreatment with the nonselective opioid antagonist naltrexone attenuated the rapid antidepressant effect of ketamine in depressed patients. The current study investigated the …

Megf10 Deficiency Impairs Skeletal Muscle Stem Cell Migration And Muscle Regeneration, Chengcheng Li, Dorianmarie Vargas-Franco, Madhurima Saha, Rachel M. Davis, Kelsey A. Manko, Isabelle Draper, Christina A. Pacak, Peter B. Kang

Faculty Publications

Biallelic loss-of-function MEGF10 mutations lead to MEGF10 myopathy, also known as early onset myopathy with areflexia, respiratory distress, and dysphagia (EMARDD). MEGF10 is expressed in muscle satellite cells, but the contribution of satellite cell dysfunction to MEGF10 myopathy is unclear. Myofibers and satellite cells were isolated and examined from Megf10 and wild-type mice. A separate set of mice underwent repeated intramuscular barium chloride injections. Megf10 muscle satellite cells showed reduced proliferation and migration, while Megf10 mouse skeletal muscles showed impaired regeneration. Megf10 deficiency is associated with impaired muscle regeneration, due in part to defects in satellite cell function. Efforts to …

Carnosic Acid Differentially Modulates The Nrf2- Antioxidant Response In Male And Female Mice Following Experimental Traumatic Brain Injury, Jacob A. Dunkerson

Theses and Dissertations--Neuroscience

Traumatic brain injury (TBI) is a leading cause of death and disability in the United States. Each year, an estimated 2.8 million Americans are diagnosed with a TBI due to falling, motor vehicle collisions, gun violence, and sports related concussions. Although inflicted by a single event, the post-traumatic effects of TBI often develop into a life-long disease. Survivors often experience cognitive decline, memory loss, emotional instability, changes in personality, and physical disabilities. A single TBI, and more-so repetitive TBI's, place an individual at a greater risk of developing chronic neurological disorders, such as dementia or Alzheimer’s disease, earlier in life. …

Prevention Of The Oncogenic Effects Of Lifestyle-Associated Advanced Glycation End-Products (Ages) Via Regular Physical Activity, Bradley A. Krisanits

MUSC Theses and Dissertations

Interrelated lifestyle factors such as a sedentary habit, obesity and diets consisting of highly processed, high protein and fat containing foods, contribute to the accumulation of reactive metabolites known as advanced glycation end-products (AGEs). AGE pathogenic effects are mediated through modification of protein function, genetic fidelity, stress responses, and aberrant cellular signaling. For the first time, this study examined the effects of dietary AGE consumption on cancer progression in vivo and assessed physical activity (PA) as a potential intervention to reduce dietary AGE mediated effects. Given the links between lifestyle and AGEs, we propose that a diet high in AGEs …

Self And Microbiota-Derived Epitopes Induce Cd4⁺ T Cell Anergy And Conversion Into Cd4⁺Foxp3⁺ Regulatory Cells, Michal P. Kuczma, Edyta A. Szurek, Anna Cebula, Vu L. Ngo, Maciej Pietrzak, Piotr Kraj, Timothy L. Denning, Leszek Ignatowicz

Biological Sciences Faculty Publications

The physiological role of T cell anergy induction as a key mechanism supporting self-tolerance remains undefined, and natural antigens that induce anergy are largely unknown. In this report, we used TCR sequencing to show that the recruitment of CD4⁺CD44⁺Foxp3⁻CD73⁺FR4⁺ anergic (Tan) cells expands the CD4⁺Foxp3⁺ (Tregs) repertoire. Next, we report that blockade in peripherally-induced Tregs (pTregs) formation due to mutation in CNS1 region of Foxp3 or chronic exposure to a selecting self-peptide result in an accumulation of Tan cells. Finally, we show that microbial antigens from Akkermansia muciniphila …

Developmental Influences On The Initial Subjective Rewarding Effects Of Etoh, Madison Waldron

Master’s Theses

The present studies were aimed to better understand developmental contributions to the risk for disordered drinking, and facilitate the long-term goal of developing effective interventions for individuals at high risk for alcohol use disorders. Experiment 1 assessed the effect of adolescent pre-exposure to ethanol on adult place preference, as well as, sex- and beta-endorphin(bE)-related contributions. Adolescent C57BL/6J and bE deficient mice were injected with 1.5g/kg of ethanol or saline and put back into their home cages. At the time of adulthood, we employed a single-exposure conditioned place preference paradigm (SE-CPP) to investigate the impact of preexposure on the initial subjective …

Will There Be Changes In Sexually Differentiated Behaviors In Mice Manipulated For The Sry Gene As They Mature Into Adultood?, Subin Joo

CMC Senior Theses

Sexually differentiated behavior has been shown to be affected by both genes and hormones. The discovery of the SRY gene, which codes for the development of testes, lead to the development of the Four Core Genotypes model of mice, and the separation of sex chromosomes and its resulting gonadal hormones. Using the FCG model, this study aims to look at the development of sexually differentiated behavior in mice, and track how it changes throughout their life. FCG mice will be divided into individual and social housing, and repeated experiments carried out to test their reaction to both intact female and …

Crucial Role Of Mammalian Glutaredoxin 3 In Cardiac Energy Metabolism In Diet-Induced Obese Mice Revealed By Transcriptome Analysis, Ninghui Cheng, Qianxing Mo, Jimmonique Donelson, Lingfei Wang, Ghislain Breton, George G Rodney, Jin Wang, Kendal D Hirschi, Xander H T Wehrens, Paul A Nakata

Children’s Nutrition Research Center Staff Publications

Obesity is often associated with metabolic dysregulation and oxidative stress with the latter serving as a possible unifying link between obesity and cardiovascular complications. Glutaredoxins (Grxs) comprise one of the major antioxidant systems in the heart. Although Grx3 has been shown to act as an endogenous negative regulator of cardiac hypertrophy and heart failure, its metabolic impact on cardiac function in diet-induced obese (DIO) mice remains largely unknown. In the present study, analysis of Grx3 expression indicated that Grx3 protein levels, but not mRNA levels, were significantly increased in the hearts of DIO mice. Cardiac-specific Grx3 deletion (Grx3 CKO) mice …

Tph2 In The Dorsal Raphe Nuclei Regulates Energy Balance In A Sex-Dependent Manner, Hailan Liu, Chunmei Wang, Meng Yu, Yongjie Yang, Yang He, Hesong Liu, Chen Liang, Longlong Tu, Nan Zhang, Lina Wang, Julia Wang, Feng Liu, Fang Hu, Yong Xu

Children’s Nutrition Research Center Staff Publications

AbstractCentral 5-hydroxytryptamine (5-HT), which is primarily synthesized by tryptophan hydroxylase 2 (TPH2) in the dorsal Raphe nuclei (DRN), plays a pivotal role in the regulation of food intake and body weight. However, the physiological functions of TPH2 on energy balance have not been consistently demonstrated. Here we systematically investigated the effects of TPH2 on energy homeostasis in adult male and female mice. We found that the DRN harbors a similar amount of TPH2+ cells in control male and female mice. Adult-onset TPH2 deletion in the DRN promotes hyperphagia and body weight gain only in male mice, but not in female …