Digital Commons Network^™

Ctcf Governs The Identity And Migration Of Mge-Derived Cortical Interneurons., Adrienne Elbert, Daniel Vogt, Ashley Watson, Michael Levy, Yan Jiang, Emilie Brûlé, Megan E Rowland, John Rubenstein, Nathalie G Bérubé

Paediatrics Publications

The CCCTC-binding factor (CTCF) is a central regulator of chromatin topology recently linked to neurodevelopmental disorders such as intellectual disability, autism, and schizophrenia. The aim of this study was to identify novel roles of CTCF in the developing mouse brain. We provide evidence that CTCF is required for the expression of the LIM homeodomain factor LHX6 involved in fate determination of cortical interneurons (CINs) that originate in the medial ganglionic eminence (MGE). Conditional

The Transcriptional Regulator Snon Promotes The Proliferation Of Cerebellar Granule Neuron Precursors In The Postnatal Mouse Brain, Xiaoying Chen, Ayan Chanda, Yoshiho Ikeuchi, Xiaoqing Zhang, Jared V. Goodman, Naveen C. Reddy, Shahriyar P. Majidi, Dennis Y. Wu, Sarah E. Smith, Abigail Godec, Anna Oldenborg, Harrison W. Gabel, Guoyan Zhao, Shirin Bonni, Azad Bonni

Open Access Publications

Control of neuronal precursor cell proliferation is essential for normal brain development, and deregulation of this fundamental developmental event contributes to brain diseases. Typically, neuronal precursor cell proliferation extends over long periods of time during brain development. However, how neuronal precursor proliferation is regulated in a temporally specific manner remains to be elucidated. Here, we report that conditional KO of the transcriptional regulator SnoN in cerebellar granule neuron precursors robustly inhibits the proliferation of these cells and promotes their cell cycle exit at later stages of cerebellar development in the postnatal male and female mouse brain. In laser capture microdissection …

Voltage-Independent Sk-Channel Dysfunction Causes Neuronal Hyperexcitability In The Hippocampus Of Fmr1 Knock-Out Mice, Pan-Yue Deng, Dan Carlin, Young Mi Oh, Leila K. Myrick, Stephen T. Warren, Valeria Cavalli, Vitaly A. Klyachko

Open Access Publications

Neuronal hyperexcitability is one of the major characteristics of fragile X syndrome (FXS), yet the molecular mechanisms of this critical dysfunction remain poorly understood. Here we report a major role of voltage-independent potassium (K

Determining Efficacy Of Anti-Cancer Drug From Detection In Plasma Using The Hplc Method, Nili Modi

BIO4950: Internship in Biology

Extraction of anti-cancer drug in plasma from in vivo organism models were studied to examine and differentiate the different methods. Along with extraction, detection of the amount and the retention period of the anti- cancer drug in plasma in the test subjects were focused on to analyze the ways of the HPLC method. The HPLC (High Performance Liquid Chromatography) method is the most frequently used method for detection in many labs due to its ability to be programed quick with minimal training and to ensure accurate results. Using animal models to detect plasma drug levels in pre-clinical trials is valuable …

Hearing Studies In Old Mice: The Effect Of Pre-Pulse Inhibition On The Acoustic Startle Response, Ashley B. Hillyard, Nicolette S. Chuss

Senior Honors Projects, 2010-2019

The purpose of this study pertains to hearing in the species Peromyscus maniculatus (deer mice) — specifically their responses to a startling sound. Approximately seven mice were tested between four and five years of age, approaching the lifespan of this species. By means of an accelerometer, which measures a reflexive, motor response, the mice were presented with an acoustic startle-eliciting stimulus (SES) — that is a loud, startling, unexpected sound. During the study, the mice were also presented with a softer, less-intense stimulus — known as a pre-pulse — slightly before the more intense sound. This pre-pulse stimulus was in …

The Loss Of Atrx Increases Susceptibility To Pancreatic Injury And Oncogenic Kras In Female But Not Male Mice., Claire C Young, Ryan M Baker, Christopher J Howlett, Todd Hryciw, Joshua E Herman, Douglas Higgs, Richard Gibbons, Howard Crawford, Arthur Brown, Christopher L Pin

Paediatrics Publications

Background

Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer death in North America, accounting for >30,000 deaths annually. Although somatic activating mutations in KRAS appear in 97% of PDAC patients, additional factors are required to initiate PDAC. Because mutations in genes encoding chromatin remodelling proteins have been implicated in KRAS-mediated PDAC, we investigated whether loss of chromatin remodeler ɑ-thalassemia, mental-retardation, X-linked (ATRX) affects oncogenic KRAS’s ability to promote PDAC. ATRX affects DNA replication, repair, and gene expression and is implicated in other cancers including glioblastomas and pancreatic neuroendocrine tumors. The hypothesis was that deletion of Atrx …

Role Of Bdnf In The Ability Of Exercise To Attenuate Dependence-Related Escalated Alcohol Drinking In C57bl/6j Mice, Matthew Gustav Solomon

MUSC Theses and Dissertations

Alcohol use disorder (AUD) continues to be a burden to society. Currently, few efficacious treatments exist. In addition to behavioral therapy and support groups (e.g. Alcoholics Anonymous), there are only three FDA approved pharmacotherapies. The lack of treatment options for alcohol addiction denotes the need to discover and develop new strategies and pharmacological targets to improve abstinence, prevent relapse, and inhibit the development of alcohol addiction. Chronic alcohol exposure reduces brain-derived neurotrophic factor (BDNF) in the medial prefrontal cortex (mPFC). Reductions of BDNF in the mPFC drive alcohol-dependent drinking in mice and conversely, elevating BDNF in this region blocks alcohol …

“Wide-Awake Drunk”: Observing The Combined Effects Of Alcohol And Caffeine On Somatic Withdrawal Signs In C57bl/6j Mice, Montana Jenkins

Undergraduate Honors Thesis Collection

Caffeine is one of the most widely used psychoactive stimulants in the world and is often used in combination with other substances. The combination of caffeine and alcohol has been shown to induce a stimulated, rather than sedated state, which may result in increased alcohol-attributable accidents (e.g., drunk driving, unprotected sex, and over intoxication). Preclinical research has found mixed results regarding the co-consumption of caffeine and alcohol – some found that caffeine increases alcohol intake while others the opposite. The current study expanded on previous research by testing the effects of combined caffeine and alcohol exposure in a binge-like, mouse …

Development Of A Neutropenic Murine Model For Invasive Candida Auris Infection, Steven Torres

Legacy Theses & Dissertations (2009 - 2024)

In less than a decade, the emerging fungal pathogen Candida auris has become a major public health threat due to its multidrug resistant (MDR) phenotype, high transmissibility, and high mortality rates that range between 30%-60%. Unlike other Candida species, C. auris has acquired high levels of resistance to an already limited arsenal of antifungals. As an emerging pathogen, there are currently a limited number of documented murine models of C. auris infection. These animal models using a range of inoculums from 105 –108 cells per mouse, and the environmental and occupational exposure of working with these models has not been …

The Effects Of Heat-Killed Echinostomatid Parasites On Mice Treated With Dextran Sodium Sulfate (Dss), Natalie Gooder

All Graduate Theses, Dissertations, and Other Capstone Projects

Objective: Autoimmune diseases are chronic, incurable, and affect approximately 50 million Americans. This is a strong need for better ways to treat autoimmune diseases. Parasites and parasite proteins have been observed to protect mice from symptoms of induced colitis in mice treated with dextran sodium sulfate (DSS), a model for inflammatory bowel disease (IBD). I hypothesize that non-living echinostomatid parasites, given during DSS treatment, can decrease intestinal inflammation and weight loss, providing a possible novel treatment for IBD.

Methods: A range of DSS concentrations (0.5%-3%) were delivered to female C57BL/6 mice in their drinking water in order to determine the …

Castration-Resistant Prostate Cancer: Androgen Receptor Inactivation Induces Telomere Dna Damage, And Damage Response Inhibition Leads To Cell Death, Vidyavathi Reddy, Asm Iskander, Clara Hwang, George Divine, Mani Menon, Evelyn R. Barrack, Prem-Veer Reddy, Sahn-Ho Kim

Urology Articles

Telomere stability is important for cell viability, as cells with telomere DNA damage that is not repaired do not survive. We reported previously that androgen receptor (AR) antagonist induces telomere DNA damage in androgen-sensitive LNCaP prostate cancer cells; this triggers a DNA damage response (DDR) at telomeres that includes activation of ATM, and blocking ATM activation prevents telomere DNA repair and leads to cell death. Remarkably, AR antagonist induces telomere DNA damage and triggers ATM activation at telomeres also in 22Rv1 castration-resistant prostate cancer (CRPC) cells that are not growth inhibited by AR antagonist. Treatment with AR antagonist enzalutamide (ENZ) …

Inflammatory Serine Proteases Play A Critical Role In The Early Pathogenesis Of Diabetic Cardiomyopathy., Mikhail A Kolpakov, Kunal Sikder, Amrita Sarkar, Shaswati Chaki, Sanket K Shukla, Xinji Guo, Zhao Qi, Carlos Barbery, Abdelkarim Sabri, Khadija Rafiq

Center for Translational Medicine Faculty Papers

BACKGROUND/AIMS: Diabetic cardiomyopathy (DCM) is characterized by structural and functional alterations that can lead to heart failure. Several mechanisms are known to be involved in the pathogenesis of DCM, however, the molecular mechanism that links inflammation to DCM is incompletely understood. To learn about this mechanism, we investigated the role of inflammatory serine proteases (ISPs) during the development of DCM.

METHODS: Eight weeks old mice with deletion of dipeptidyl peptidase I (DPPI), an enzyme involved in the maturation of major ISPs, and wild type (WT) mice controls were injected with streptozotocin (50 mg/kg for 5 days intraperitoneally) and studied after …

Role Of Glial Glutamate Transporter In Animal Model Of Acute And Chronic Inflammatory Pain, Ghallab Alotaibi

Electronic Theses and Dissertations

No abstract provided.

Mice And Rats: Perceptions, Realities, And Impacts On Humankind, Terry A. Messmer

Human–Wildlife Interactions

This is the Letter from the Editor.

Acute And Repeated Effects Of Synthetic Cannabinoid Agonism And Cannabinoid Receptor 1 Positive Allosteric Modulation, Kristen R. Trexler

Graduate Theses, Dissertations, and Problem Reports (ETD)

Recent years have seen a rise in the diversity and use of synthetic cannabinoids. Currently, there is little known about the effects of specific synthetic cannabinoid compounds. As such, little research has been done evaluating the acute and chronic effects of synthetic cannabinoid administration or the development of tolerance and withdrawal. The present study aimed, in part, to evaluate the acute and repeated effect of a third-generation synthetic cannabinoid, AB-FUBINACA. Mice were treated with AB-FUBINACA (0.1-3 mg/kg, i.p.) or vehicle and were tested repeatedly in the tetrad battery of assays, which included tests of catalepsy, antinociception, hypothermia, and locomotor activity. …

Mitochondrial Superoxide Disrupts The Metabolic And Epigenetic Landscape Of Cd4, Cassandra M. Moshfegh, Christopher W. Collins, Venugopal Gunda, A. Vasanthakumar, J. Z. Cao, Pankaj K. Singh, L. A. Godley, Adam J. Case

Journal Articles: Eppley Institute

While the role of mitochondrial metabolism in controlling T-lymphocyte activation and function is becoming more clear, the specifics of how mitochondrial redox signaling contributes to T-lymphocyte regulation remains elusive. Here, we examined the global effects of elevated mitochondrial superoxide (O₂^-) on T-lymphocyte activation using a novel model of inducible manganese superoxide dismutase (MnSOD) knock-out. Loss of MnSOD led to specific increases in mitochondrial O₂^- with no evident changes in hydrogen peroxide (H₂O₂), peroxynitrite (ONOO^-), or copper/zinc superoxide dismutase (CuZnSOD) levels. Unexpectedly, both mitochondrial and glycolytic metabolism showed significant reductions …

Inhibition Of Geranylgeranyl Diphosphate Synthase Is A Novel Therapeutic Strategy For Pancreatic Ductal Adenocarcinoma, Staci L. Haney, Michelle L. Varney, Yashpal S. Chhonker, Simon Shin, Kamiya Mehla, Ayrianne J. Crawford, Heather Jensen Smith, Lynette M. Smith, Daryl J. Murry, Michael A. Hollingsworth, Sarah A. Holstein

Journal Articles: Eppley Institute

Rab proteins play an essential role in regulating intracellular membrane trafficking processes. Rab activity is dependent upon geranylgeranylation, a post-translational modification that involves the addition of 20-carbon isoprenoid chains via the enzyme geranylgeranyl transferase (GGTase) II. We have focused on the development of inhibitors against geranylgeranyl diphosphate synthase (GGDPS), which generates the isoprenoid donor (GGPP), as anti-Rab agents. Pancreatic ductal adenocarcinoma (PDAC) is characterized by abnormal mucin production and these mucins play important roles in tumor development, metastasis and chemo-resistance. We hypothesized that GGDPS inhibitor (GGDPSi) treatment would induce PDAC cell death by disrupting mucin trafficking, thereby inducing the unfolded …

Pancreas Of Coxsackievirus-Infected Dams And Their Challenged Pups: A Complex Issue, Sona Sarmirova, Maria Borsanyiova, Brigita Benkoova, Michaela Pospisilova, Rajkumar Rajasekaran, Katarina Berakova, Pavol Gomolcak, Jay Reddy, Shubhada Bopegamage

School of Veterinary and Biomedical Sciences: Faculty Publications

Enteroviral infections are frequent, often asymptomatic in humans and during gravidity. The present study is an extension of our previous investigations where we had shown pancreatitis in challenged pups of CVB4-E2-infected dams. Present investigation describes the effect of gestational infection with this virus on the pancreas of both dams and their challenged pups. Gravid CD1 outbred mice were orally infected with CVB4-E2 virus at different gestation times. Pups were challenged orally with the same virus after 25 days of birth. Organs were collected at selected intervals postinfection (p.i.), and replicating virus and viral-RNA copies were analyzed. Additional readouts included histopathology …

Modeling Cell Line-Specific Recruitment Of Signaling Proteins To The Insulin-Like Growth Factor 1 Receptor, Keesha E. Erickson, Dipak Barua, For Full List Of Authors, See Publisher's Website.

Chemical and Biochemical Engineering Faculty Research & Creative Works

Receptor tyrosine kinases (RTKs) typically contain multiple autophosphorylation sites in their cytoplasmic domains. Once activated, these autophosphorylation sites can recruit downstream signaling proteins containing Src homology 2 (SH2) and phosphotyrosine-binding (PTB) domains, which recognize phosphotyrosine-containing short linear motifs (SLiMs). These domains and SLiMs have polyspecific or promiscuous binding activities. Thus, multiple signaling proteins may compete for binding to a common SLiM and vice versa. To investigate the effects of competition on RTK signaling, we used a rule-based modeling approach to develop and analyze models for ligand-induced recruitment of SH2/PTB domain-containing proteins to autophosphorylation sites in the insulin-like growth factor 1 …

Melatonin Enhances Sorafenib-Induced Cytotoxicity In Flt3-Itd Acute Myeloid Leukemia Cells By Redox Modification, Tian Tian, Jiajun Li, Yizhuo Li, Yun-Xin Lu, Yan-Lai Tang, Hua Wang, Fufu Zheng, Dingbo Shi, Qian Long, Miao Chen, Guillermo Garcia-Manero, Yumin Hu, Lijun Qin, Wuguo Deng

Faculty, Staff and Student Publications

Acute myeloid leukemia (AML) with an internal tandem duplication in Fms-related tyrosine kinase 3 (FLT3-ITD) is identified as a subgroup with poor outcome and intrinsic resistance to chemotherapy and therefore urgent need for development of novel therapeutic strategies.

Methods: The antitumor effects of melatonin alone or combined with sorafenib were evaluated via flow cytometry and immunoblotting assays in FLT-ITD AML cells. Also, the ex vivo and in vivo models were used to test the synergistic effects of melatonin and sorafenib against leukemia with FLT3/ITD mutation.

Results: Our study shows for the first time that melatonin inhibits proliferation and induces apoptosis …

A Potential New Tool For The Toolbox: Assessing Gene Drives For Eradicating Invasive Rodent Populations, K. J. Campbell, J.R. Saah, P.R. Brown, J. Godwin, G.R. Howald, A. Piaggio, P. Thomas, D.M. Tompkins, D. Threadgill, J. Delborne, D.M. Kanavy, T. Kuiken, H. Packard, M. Serr, A. Shiels

United States Department of Agriculture Wildlife Services: Staff Publications

Invasive rodents have significant negative impacts on island biodiversity. All but the smallest of rodent eradications currently rely on island-wide rodenticide applications. Although significant advances have been made in mitigating unintended impacts, rodent eradication on inhabited islands remains extremely challenging. Current tools restrict eradication eff orts to fewer than 15% of islands with critically endangered or endangered species threatened by invasive rodents. The Genetic Biocontrol of Invasive Rodents partnership is an interdisciplinary collaboration to develop and evaluate gene drive technology for eradicating invasive rodent populations on islands. Technological approaches currently being investigated include the production of multiple strains of Mus …

Viral Mhci Inhibition Evades Tissue-Resident Memory T Cell Formation And Responses, Elvin J. Lauron, Liping Yang, Ian B. Harvey, Dorothy K. Sojka, Graham D. Williams, Michael A. Paley, Michael D. Bern, Eugene Park, Francisco Victorino, Adrianus C.M. Boon, Wayne M. Yokoyama

Open Access Publications

Tissue-resident memory CD8

Evaluating The Effects Of Antibody-Conjugated Multi-Walled Carbon Nanotubes In Combination With Microwave Irradiation, Amy Chall

College of Graduate Studies: Theses & Dissertations

Cancer remains one of the largest public health concerns of our day, particularly in developed countries where technological advances have allowed populations to live well into their eighth decade. In America, those in their 80’s have a 1 in 2 chance of developing cancer in their lifetime. Prostate cancer, specifically is the second leading cause of cancer deaths in males. Traditional cancer therapies cause high levels of toxicity to the patient due to mechanisms of action that often attack cancer cells and healthy cells alike. The holy grail of cancer research is to find a treatment that targets the cancer …

Squalene Attenuates The Oxidative Stress And Activates Akt/Mtor Pathway Against Cisplatin-Induced Kidney Damage In Mice, Ayşe Arzu Şakul, Mehmet Ozansoy, Bi̇rsen Eli̇bol, Şule Ayla, Mehmet Yalçin Günal, Yasemi̇n Yozgat, Selma Hüveyda Başağa, Kazi̇m Şahi̇n, Rümeyza Kazancioğlu, Ülkan Kiliç

Turkish Journal of Biology

The clinical use of cisplatin, which is a first-line anticancer agent, is highly restricted due to its adverse effects on kidneys that lead to nephrotoxicity. Therefore, some potential reno-protective substances have been used in combination with cisplatin to cope with nephrotoxicity. Due to its high antitumor activity and oxygen-carrying capacity, we investigated the molecular effects of squalene against cisplatin-induced oxidative stress and kidney damage in mice. Single dose of cisplatin (7 mg/kg) was given to male Balb/c mice. Squalene (100 mg/kg/day) was administered orogastrically to mice for 10 days. Following sacrification, molecular alterations were investigated as analysis of the levels …

Resveratrol Attenuates Allergic Asthma And Associated Inflammation In The Lungs Through Regulation Of Mirna-34a That Targets Foxp3 In Mice, Esraah Alharris, Hasan Alghetaa, Ratanesh K. Seth, Saurabh Chatterjee, Narendra P. Singh, Mitzi Nagarkatti, Prakash Nagarkatti

Faculty Publications

Asthma is a chronic inflammatory disease of airways mediated by T-helper 2 (Th2) cells involving complex signaling pathways. Although resveratrol has previously been shown to attenuate allergic asthma, the role of miRNA in this process has not been studied. We investigated the effect of resveratrol on ovalbumin-induced experimental allergic asthma in mice. To that end, BALB/c mice were immunized with ovalbumin (OVA) intraperitoneally followed by oral gavage of vehicle (OVA-veh) or resveratrol (100 mg/kg body) (OVA-res). On day 7, the experimental groups received intranasal challenge of OVA followed by 7 days of additional oral gavage of vehicle or resveratrol. At …

Als Mutations Of Fus Suppress Protein Translation And Disrupt The Regulation Of Nonsense-Mediated Decay, Marisa Kamelgarn, Jing Chen, Lisha Kuang, Huan Jin, Edward J. Kasarskis, Haining Zhu

Toxicology and Cancer Biology Faculty Publications

Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease characterized by preferential motor neuron death. Approximately 15% of ALS cases are familial, and mutations in the fused in sarcoma (FUS) gene contribute to a subset of familial ALS cases. FUS is a multifunctional protein participating in many RNA metabolism pathways. ALS-linked mutations cause a liquid–liquid phase separation of FUS protein in vitro, inducing the formation of cytoplasmic granules and inclusions. However, it remains elusive what other proteins are sequestered into the inclusions and how such a process leads to neuronal dysfunction and degeneration. In this study, we developed …

Rare But Recurrent Ros1 Fusions Resulting From Chromosome 6q22 Microdeletions Are Targetable Oncogenes In Glioma., Monika A Davare, Jacob J Henderson, Anupriya Agarwal, Jacob P Wagner, Sudarshan R Iyer, Nameeta Shah, Randy Woltjer, Romel Somwar, Stephen W Gilheeney, Ana Decarvalo, Tom Mikkelson, Erwin G Van Meir, Marc Ladanyi, Brian J Druker

Articles, Abstracts, and Reports

PURPOSE: Gliomas, a genetically heterogeneous group of primary central nervous system tumors, continue to pose a significant clinical challenge. Discovery of chromosomal rearrangements involving kinase genes has enabled precision therapy, and improved outcomes in several malignancies.

EXPERIMENTAL DESIGN: Positing that similar benefit could be accomplished for patients with brain cancer, we evaluated The Cancer Genome Atlas (TCGA) glioblastoma dataset. Functional validation of the oncogenic potential and inhibitory sensitivity of discovered ROS1 fusions was performed using three independent cell-based model systems, and an

RESULTS:

CONCLUSIONS: Our findings highlight that CNS tumors should be specifically interrogated for these rare intrachromosomal 6q22 microdeletion …

Clinical Pharmacology Of Tisagenlecleucel In B-Cell Acute Lymphoblastic Leukemia., Karen Thudium Mueller, Edward Waldron, Stephan A. Grupp, John E. Levine, Theodore W. Laetsch, Michael A. Pulsipher, Michael W. Boyer, Keith August, Jason Hamilton, Rakesh Awasthi, Andrew M. Stein, Denise Sickert, Abhijit Chakraborty, Bruce L. Levine, Carl H. June, Lori Tomassian, Sweta S. Shah, Mimi Leung, Tetiana Taran, Patricia A. Wood, Shannon L. Maude

Manuscripts, Articles, Book Chapters and Other Papers

PURPOSE: Tisagenlecleucel is an anti-CD19 chimeric antigen receptor (CAR19) T-cell therapy approved for the treatment of children and young adults with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL).

PATIENTS AND METHODS: We evaluated the cellular kinetics of tisagenlecleucel, the effect of patient factors, humoral immunogenicity, and manufacturing attributes on its kinetics, and exposure-response analysis for efficacy, safety and pharmacodynamic endpoints in 79 patients across two studies in pediatric B-ALL (ELIANA and ENSIGN).

RESULTS: Using quantitative polymerase chain reaction to quantify levels of tisagenlecleucel transgene, responders (N = 62) had ≈2-fold higher tisagenlecleucel expansion in peripheral blood than nonresponders ( …

Born In The Wild: Baby Mammals And Their Parents, Sarah Rawle

Children's Book and Media Review

Did you know that mama pandas cradle their babies for the first several days of their life, without even putting them down to eat or drink? Did you know that baby wolves need to have their moms chew their food? Read to learn more about baby wild animals and their mothers!

A High-Fat Diet Alters Genome-Wide Dna Methylation And Gene Expression In Sm/J Mice, Madeline R. Keleher, Rabab Zaidi, Lauren Hicks, Shyam Shah, Xiaoyun Xing, Daofeng Li, Ting Wang, James M. Cheverud

Biology: Faculty Publications and Other Works

Background: While the genetics of obesity has been well defined, the epigenetics of obesity is poorly understood. Here, we used a genome-wide approach to identify genes with differences in both DNA methylation and expression associated with a high-fat diet in mice. Results: We weaned genetically identical Small (SM/J) mice onto a high-fat or low-fat diet and measured their weights weekly, tested their glucose and insulin tolerance, assessed serum biomarkers, and weighed their organs at necropsy. We measured liver gene expression with RNA-seq (using 21 total libraries, each pooled with 2 mice of the same sex and diet) and DNA methylation …