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Assessing Sex-Specific Circadian, Metabolic, And Cognitive Phenotypes In The Aβpp/Ps1 And Appnl-F/Nl-F Models Of Alzheimer's Disease., Jesse Britz, Emmanuel Ojo, Asmita Dhukhwa, Takashi Saito, Takaomi C Saido, Erin R Hascup, Kevin N Hascup, Shelley A Tischkau

Articles

BACKGROUND: Circadian disruption has long been recognized as a symptom of Alzheimer's disease (AD); however, emerging data suggests that circadian dysfunction occurs early on in disease development, potentially preceding any noticeable cognitive deficits.

OBJECTIVE: This study compares the onset of AD in male and female wild type (C57BL6/J), transgenic (AβPP/PS1), and knock-in (APPNL-F/NL-F) AD mouse models from the period of plaque initiation (6 months) through 12 months.

METHODS: Rhythmic daily activity patterns, glucose sensitivity, cognitive function (Morris water maze, MWM), and AD pathology (plaques formation) were assessed. A comparison was made across sexes.

RESULTS: Sex-dependent hyperactivity in AβPP/PS1 mice was …

Assessing Sex-Specific Circadian, Metabolic, And Cognitive Phenotypes In The Aβpp/Ps1 And Appnl-F/Nl-F Models Of Alzheimer's Disease., Jesse Britz, Emmanuel Ojo, Asmita Dhukhwa, Takashi Saito, Takaomi C Saido, Erin R Hascup, Kevin N Hascup, Shelley A Tischkau

Articles

BACKGROUND: Circadian disruption has long been recognized as a symptom of Alzheimer's disease (AD); however, emerging data suggests that circadian dysfunction occurs early on in disease development, potentially preceding any noticeable cognitive deficits.

OBJECTIVE: This study compares the onset of AD in male and female wild type (C57BL6/J), transgenic (AβPP/PS1), and knock-in (APPNL-F/NL-F) AD mouse models from the period of plaque initiation (6 months) through 12 months.

METHODS: Rhythmic daily activity patterns, glucose sensitivity, cognitive function (Morris water maze, MWM), and AD pathology (plaques formation) were assessed. A comparison was made across sexes.

RESULTS: Sex-dependent hyperactivity in AβPP/PS1 mice was …

Amigo1 Promotes Axon Growth And Territory Matching In The Retina, Florentina Soto, Ning Shen, Daniel Kerschensteiner

Open Access Publications

Dendrite and axon arbor sizes are critical to neuronal function and vary widely between different neuron types. The relative dendrite and axon sizes of synaptic partners control signal convergence and divergence in neural circuits. The developmental mechanisms that determine cell-type-specific dendrite and axon size and match synaptic partners' arbor territories remain obscure. Here, we discover that retinal horizontal cells express the leucine-rich repeat domain cell adhesion molecule AMIGO1. Horizontal cells provide pathway-specific feedback to photoreceptors-horizontal cell axons to rods and horizontal cell dendrites to cones. AMIGO1 selectively expands the size of horizontal cell axons. When

Animal Source Foods, Rich In Essential Amino Acids, Are Important For Linear Growth And Development Of Young Children In Low- And Middle-Income Countries, Panam Parikh, Richard Semba, Mark Manary, Sumathi Swaminathan, Emorn Udomkesmalee, Rolf Bos, Bee Koon Poh, Nipa Rojroongwasinkul, Jan Geurts, Rini Sekartini, Tran Thuy Nga

2020-Current year OA Pubs

Growth faltering under 5 years of age is unacceptably high worldwide, and even more children, while not stunted, fail to reach their growth potential. The time between conception and 2 years of age is critical for development. The period from 6 to 23 months, when complementary foods are introduced, coincides with a time when growth faltering and delayed neurocognitive developments are most common. Fortunately, this is also the period when diet exercises its greatest influence. Growing up in an adverse environment, with a deficient diet, as typically seen in low- and middle-income countries (LMICs), hampers growth and development of children …

Wormbase In 2022-Data, Processes, And Tools For Analyzing Caenorhabditis Elegans, Paul Davis, Tim Schedl, Et Al

Open Access Publications

WormBase (www.wormbase.org) is the central repository for the genetics and genomics of the nematode Caenorhabditis elegans. We provide the research community with data and tools to facilitate the use of C. elegans and related nematodes as model organisms for studying human health, development, and many aspects of fundamental biology. Throughout our 22-year history, we have continued to evolve to reflect progress and innovation in the science and technologies involved in the study of C. elegans. We strive to incorporate new data types and richer data sets, and to provide integrated displays and services that avail the knowledge generated by the …

Genomic Degeneration And Reduction In The Fish Pathogen Mycobacterium Shottsi, David T. Gauthier, Janis H. Doss, M. Lagatta, T. Gupta, R.K. Karls, F. D. Quinn

Biological Sciences Faculty Publications

Mycobacterium shottsii is a dysgonic, nonpigmented mycobacterium originally isolated from diseased striped bass (Morone saxatilis) in the Chesapeake Bay, USA. Genomic analysis reveals that M. shottsii is a Mycobacterium ulcerans/Mycobacterium marinum clade (MuMC) member, but unlike the superficially similar M. pseudoshottsii, also isolated from striped bass, it is not an M. ulcerans ecovar, instead belonging to a transitional group of strains basal to proposed “Aronson” and “M” lineages. Although phylogenetically distinct from the human pathogen M. ulcerans, the M. shottsii genome shows parallel but nonhomologous genomic degeneration, including massive accumulation of pseudogenes accompanied by proliferation of …

Rickettsial Pathogen Perturbs Tick Circadian Gene To Infect The Vertebrate Host, Supreet Khanal, Vikas Taank, John F. Anderson, Hameeda Sultana, Girish Neelakanta

Biological Sciences Faculty Publications

Ixodes scapularis is a medically important tick that transmits several microbes to humans, including rickettsial pathogen Anaplasma phagocytophilum. In nature, these ticks encounter several abiotic factors including changes in temperature, humidity, and light. Many organisms use endogenously generated circadian pathways to encounter abiotic factors. In this study, we provide evidence for the first time to show that A. phagocytophilum modulates the arthropod circadian gene for its transmission to the vertebrate host. We noted a circadian oscillation in the expression of arthropod clock, bmal1, period and timeless genes when ticks or tick cells were exposed to alternate 12 h …

Ret Signaling Pathway And Ret Inhibitors In Human Cancer, Angelina T Regua, Mariana Najjar, Hui-Wen Lo

Faculty, Staff and Student Publications

Rearranged during transfection (RET) receptor tyrosine kinase was first identified over thirty years ago as a novel transforming gene. Since its discovery and subsequent pathway characterization, RET alterations have been identified in numerous cancer types and are most prevalent in thyroid carcinomas and non-small cell lung cancer (NSCLC). In other tumor types such as breast cancer and salivary gland carcinomas, RET alterations can be found at lower frequencies. Aberrant RET activity is associated with poor prognosis of thyroid and lung carcinoma patients, and is strongly correlated with increased risk of distant metastases. RET aberrations encompass a variety of genomic or …

Defining "Habitat" Post-Weyerhaeuser: Critical Habitat Regulations Under The Endangered Species Act Must Promote Species Recovery, Nate Mccabe

American University Law Review

As one of the strongest federal environmental statutes, the Endangered Species Act (ESA) is a powerful tool for environmental litigators to uphold the important conservation objectives articulated by Congress in 1973. In recent years, the role of “critical habitat” within the ESA has come into question. The Supreme Court decided in Weyerhaeuser that “critical habitat” must also qualify as “habitat,” but it failed to articulate any guidelines for determining what “habitat” actually is. This decision incited a regulatory tug-of-war over the proper definition of “habitat” within the ESA. This Comment explores the approaches to defining “habitat” employed by the Trump …

Gut Microbiome Dysbiosis In Antibiotic-Treated Covid-19 Patients Is Associated With Microbial Translocation And Bacteremia, Lucie Bernard-Raichon, Mericien Venzon, Jon Klein, Jordan E. Axelrad, Chenzhen Zhang, Alexis P. Sullivan, Grant A. Hussey, Arnau Casanovas-Massana, Maria G. Noval, Ana M. Valero-Jimenez, Juan Gago, Gregory Putzel, Alejandro Pironti, Evan Wilder, Yale Impact Research Team, Lorna E. Thorpe, Dan R. Littman, Meike Dittmann, Kenneth A. Stapleford, Bo Shopsin, Victor J. Torres, Albert I. Ko, Akiko Iwasaki, Ken Cadwell, Jonas Schluter, Abeer Obaid, Alice Lu-Culligan, Allison Nelson, Anderson Brito, Angela Nunez, Anjelica Martin, Annie Watkins, Bertie Geng, Chaney Kalinich, Christina Harden, Codruta Todeasa, Cole Jensen, Daniel Kim, David Mcdonald, Denise Shepard, Edward Courchaine, Elizabeth B. White, Eric Song, Erin Silva, Eriko Kudo, Giuseppe Deluliis, Harold Rahming, Hong-Jai Park, Irene Matos, Jessica Nouws, Jordan Valdez, Joseph R. Fauver, Joseph Lim, Kadi-Ann Rose, Kelly Anastasio, Kristina Brower, Laura Glick, Lokesh Sharma, Lorenzo Sewanan, Lynda Knaggs, Maksym Minasyan, Maria Batsu, Mary Petrone, Maxine Kuang, Maura Nakahata, Melissa Campbell, Melissa Linehan, Michael H. Askenase, Michael Simonov, Mikhail Smolgovsky, Nicole Sonnert, Nida Naushad

Journal Articles: Epidemiology

Although microbial populations in the gut microbiome are associated with COVID-19 severity, a causal impact on patient health has not been established. Here we provide evidence that gut microbiome dysbiosis is associated with translocation of bacteria into the blood during COVID-19, causing life-threatening secondary infections. We first demonstrate SARS-CoV-2 infection induces gut microbiome dysbiosis in mice, which correlated with alterations to Paneth cells and goblet cells, and markers of barrier permeability. Samples collected from 96 COVID-19 patients at two different clinical sites also revealed substantial gut microbiome dysbiosis, including blooms of opportunistic pathogenic bacterial genera known to include antimicrobial-resistant species. …

Environmentally-Triggered Contraction Of The Norovirus Virion Determines Diarrheagenic Potential, Emily W Helm, Elizabeth A Kennedy, Megan T Baldridge, Et Al.

2020-Current year OA Pubs

Noroviruses are the leading cause of severe childhood diarrhea and foodborne disease worldwide. While they are a major cause of disease in all age groups, infections in the very young can be quite severe with annual estimates of 50,000-200,000 fatalities in children under 5 years old. In spite of the remarkable disease burden associated with norovirus infections in people, very little is known about the pathogenic mechanisms underlying norovirus diarrhea, principally because of the lack of tractable small animal models. We recently demonstrated that wild-type neonatal mice are susceptible to murine norovirus (MNV)-induced acute self-resolving diarrhea in a time course …

Cancer Vaccines From Cryogenically Silicified Tumour Cells Functionalized With Pathogen-Associated Molecular Patterns, Jimin Guo, Henning De May, Stefan Franco, Achraf Noureddine, Lien Tang, C J. Brinker, Donna F. Kusewitt, Sarah F. Adams, Rita E. Serda

Pathology Research and Scholarship

The production of personalized cancer vaccines made from autologous tumour cells could benefit from mechanisms that enhance immunogenicity. Here we show that cancer vaccines can be made via the cryogenic silicification of tumour cells, which preserves tumour antigens within nanoscopic layers of silica, followed by the decoration of the silicified surface with pathogen-associated molecular patterns. These pathogen-mimicking cells activate dendritic cells and enhance the internalization, processing and presentation of tumour antigens to T cells. In syngeneic mice with high-grade ovarian cancer, a cell-line-based silicified cancer vaccine supported the polarization of CD4⁺ T cells towards the T-helper-1 phenotype in the …

Uveitis-Mediated Immune Cell Invasion Through The Extracellular Matrix Of The Lens Capsule, Jodirae Dedreu, Sonali Pal-Ghosh, Mary J Mattapallil, Rachel R Caspi, Mary Ann Stepp, A Sue Menko

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

While the eye is considered an immune privileged site, its privilege is abrogated when immune cells are recruited from the surrounding vasculature in response to trauma, infection, aging, and autoimmune diseases like uveitis. Here, we investigate whether in uveitis immune cells become associated with the lens capsule and compromise its privilege in studies of C57BL/6J mice with experimental autoimmune uveitis. These studies show that at D14, the peak of uveitis in these mice, T cells, macrophages, and Ly6G/Ly6C+ immune cells associate with the lens basement membrane capsule, burrow into the capsule matrix, and remain integrated with the capsule as immune …

Depletion And Enrichment Of Phytosterols In Soybean Oil Lipid Emulsions Directly Associate With Serum Markers Of Cholestasis In Preterm Parenteral Nutrition-Fed Pigs, Greg Guthrie, Barbara Stoll, Shaji Chacko, Mahmoud Mohammad, Candace Style, Mariatu Verla, Oluyinka Olutoye, Deborah Schady, Charlotte Lauridsen, Nick Tataryn, Douglas Burrin

Children’s Nutrition Research Center Staff Publications

Background: Clinical reports show a positive correlation between phytosterol concentrations and severity of cholestatic liver disease markers in infants during long-term administration of parenteral lipid emulsions. Establishing a causal link between phytosterols and cholestasis has been complicated by confounding factors of lipid emulsion load, fatty acid composition, and vitamin E in many of these studies. The goal of this study is to determine whether altering the phytosterol concentration within a common soybean oil-based emulsion will alter the onset and severity of cholestasis in parenterally fed preterm piglets.

Methods: Preterm piglets were administered, for 21 days, either enteral nutrition (ENT) or …

Gabra5 Plays A Sexually Dimorphic Role In Pomc Neuron Activity And Glucose Balance, Zhou Pei, Yang He, Jonathan C Bean, Yongjie Yang, Hailan Liu, Meng Yu, Kaifan Yu, Ilirjana Hyseni, Xing Cai, Hesong Liu, Na Qu, Longlong Tu, Kristine M Conde, Mengjie Wang, Yongxiang Li, Na Yin, Nan Zhang, Junying Han, Camille Hs Potts, Nikolas A Scarcelli, Zili Yan, Pingwen Xu, Qi Wu, Yanlin He, Yong Xu, Chunmei Wang

Children’s Nutrition Research Center Staff Publications

Pro-opiomelanocortin (POMC) neurons are important for the regulation of body weight and glucose balance. The inhibitory tone to POMC neurons is mediated primarily by the GABA receptors. However, the detailed mechanisms and functions of GABA receptors are not well understood. The α5 subunit of GABAA receptor, Gabra5, is reported to regulate feeding, and we found that Gabra5 is highly expressed in POMC neurons. To explore the function of Gabra5 in POMC neurons, we knocked down Gabra5 specifically from mature hypothalamic POMC neurons using the clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 strategy. This POMC-specific knock-down of Gabra5 did not affect …

Tissue-Specific Mechanisms Of Bile Acid Homeostasis And Activation Of Fxr-Fgf19 Signaling In Preterm And Term Neonatal Pigs, Caitlin Vonderohe, Greg Guthrie, Barbara Stoll, Shaji Chacko, Harry Dawson, Douglas G Burrin

Children’s Nutrition Research Center Staff Publications

The tissue-specific molecular mechanisms involved in perinatal liver and intestinal farnesoid X receptor (FXR)-fibroblast growth factor 19 (FGF19) signaling are poorly defined. Our aim was to establish how gestational age and feeding status affect bile acid synthesis pathway, bile acid pool size, ileal response to bile acid stimulation, genes involved in bile acid-FXR-FGF19 signaling and plasma FGF19 in neonatal pigs. Term (n = 23) and preterm (n = 33) pigs were born via cesarean section at 100% and 90% gestation, respectively. Plasma FGF19, hepatic bile acid and oxysterol profiles, and FXR target gene expression were assessed in pigs …

Other Orchards, Sam B. Robison

Graduate Student Theses, Dissertations, & Professional Papers

Other Orchards is comprised of poems each suspect in their own way of those boundaries that might separate humans from nature, rural from urban, worker from scholar, or human from beast. Using the figure of the orchard, a kind of “false forest,” this collection studies the ways we map ourselves onto our work and the way work might inform an understanding of the self. Ultimately, these are poems that emerge from the seams of things—the shoulder of highway strewn with dead antelope, the feral apple tree lost to the woods, the farmer lost in their work, slowing becoming less and …

Investigation Of Urinary Metabolomics In A Phase I Hookworm Vaccine Trial In Gabon, Madeleine Eunice Betouke Ongwe, Yoanne D Mouwenda, Koen A Stam, Peter G Kremsner, Bertrand Lell, David Diemert, Jeff Bethony, Maria E Bottazzi, Peter J Hotez, Remko V Leeuwen, Martin P Grobusch, Ayola A Adegnika, Oleg A Mayboroda, Maria Yazdanbakhsh

Center for Medical Ethics and Health Policy Staff Publications

Metabolomics provides a powerful tool to study physiological changes in response to various perturbations such as vaccination. We explored whether metabolomic changes could be seen after vaccination in a phase I trial where Gabonese adults living either in rural or semi-urban areas received the subunit hookworm vaccine candidates (Na-GST-1 and Na-APR-1 (M74) adjuvanted with Alhydrogel plus GLA-AF (n = 24) or the hepatitis B vaccine (n = 8) as control. Urine samples were collected and assayed using targeted 1H NMR spectroscopy. At baseline, a set of metabolites significantly distinguished rural from semi-urban individuals. The pre- and post-vaccination comparisons indicated significant …

Anti-Grp-R Monoclonal Antibody Antitumor Therapy Against Neuroblastoma, Jingbo Qiao, Junquan Liu, Jillian C Jacobson, Rachael A Clark, Sora Lee, Li Liu, Zhiqiang An, Ningyan Zhang, Dai H Chung

Faculty, Staff and Student Publications

Standard treatment for patients with high-risk neuroblastoma remains multimodal therapy including chemoradiation, surgical resection, and autologous stem cell rescue. Immunotherapy has demonstrated success in treating many types of cancers; however, its use in pediatric solid tumors has been limited by low tumor mutation burdens. Gastrin-releasing peptide receptor (GRP-R) is overexpressed in numerous malignancies, including poorly-differentiated neuroblastoma. Monoclonal antibodies (mAbs) to GRP-R have yet to be developed but could serve as a potential novel immunotherapy. This preclinical study aims to evaluate the efficacy of a novel GRP-R mAb immunotherapy against neuroblastoma. We established four candidate anti-GRP-R mAbs by screening a single-chain …

Where Should Conservation Draw The Line And When Should It Push Forward, Jessica L. Mejia

Graduate Student Theses, Dissertations, & Professional Papers

No abstract provided.

Loss Of Mmr And Tgfbr2 Increases The Susceptibility To Microbiota-Dependent Inflammation-Associated Colon Cancer, Elena Tosti, Ana S Almeida, Tam T T Tran, Mariel Barbachan E Silva, Pilib Ó Broin, Robert Dubin, Ken Chen, Amanda P Beck, Andrew S Mclellan, Eduardo Vilar, Aaron Golden, Paul W O'Toole, Winfried Edelmann

Faculty, Staff and Student Publications

Background and aims: Mutations in DNA mismatch repair (MMR) genes are causative in Lynch syndrome and a significant proportion of sporadic colorectal cancers (CRCs). MMR-deficient (dMMR) CRCs display increased mutation rates, with mutations frequently accumulating at short repetitive DNA sequences throughout the genome (microsatellite instability). The TGFBR2 gene is one of the most frequently mutated genes in dMMR CRCs. Therefore, we generated an animal model to study how the loss of both TGFBR2 signaling impacts dMMR-driven intestinal tumorigenesis in vivo and explore the impact of the gut microbiota.

Methods: We generated VCMsh2/Tgfbr2 mice in which Msh2loxP and Tgfbr2loxP alleles are …

Advances And Gaps In Sars-Cov-2 Infection Models, César Muñoz-Fontela, Michael S. Diamond, Et Al

Open Access Publications

The global response to Coronavirus Disease 2019 (COVID-19) is now facing new challenges such as vaccine inequity and the emergence of SARS-CoV-2 variants of concern (VOCs). Preclinical models of disease, in particular animal models, are essential to investigate VOC pathogenesis, vaccine correlates of protection and postexposure therapies. Here, we provide an update from the World Health Organization (WHO) COVID-19 modeling expert group (WHO-COM) assembled by WHO, regarding advances in preclinical models. In particular, we discuss how animal model research is playing a key role to evaluate VOC virulence, transmission and immune escape, and how animal models are being refined to …

The Mutationathon Highlights The Importance Of Reaching Standardization In Estimates Of Pedigree-Based Germline Mutation Rates, Lucie A. Bergeron, Tychele Turner, Et Al

Open Access Publications

In the past decade, several studies have estimated the human per-generation germline mutation rate using large pedigrees. More recently, estimates for various nonhuman species have been published. However, methodological differences among studies in detecting germline mutations and estimating mutation rates make direct comparisons difficult. Here, we describe the many different steps involved in estimating pedigree-based mutation rates, including sampling, sequencing, mapping, variant calling, filtering, and appropriately accounting for false-positive and false-negative rates. For each step, we review the different methods and parameter choices that have been used in the recent literature. Additionally, we present the results from a 'Mutationathon,' a …

Intrinsic Mechanisms In The Gating Of Resurgent Na+ Currents, Joseph L. Ransdell, Jonathan D. Moreno, Druv Bhagavan, Jonathan R. Silva, Jeanne M. Nerbonne

Open Access Publications

The resurgent component of the voltage-gated sodium current (I

Loss Of Kmt2c Reprograms The Epigenomic Landscape In Hpscs Resulting In Nodal Overexpression And A Failure Of Hemogenic Endothelium Specification, Shailendra Maurya, Wei Yang, Minori Tamai, Qiang Zhang, Petra Erdmann-Gilmore, Amelia Bystry, Fernanda Martins Rodrigues, Mark C Valentine, Wing H Wong, Reid Townsend, Todd E Druley

Open Access Publications

Germline or somatic variation in the family of KMT2 lysine methyltransferases have been associated with a variety of congenital disorders and cancers. Notably,

Steroid Hormone Signaling Activates Thermal Nociception During Drosophila Peripheral Nervous System Development, Jacob S. Jaszczak, Laura Devault, Lily Yeh Jan, Yuh Nung Jan

Open Access Publications

Sensory neurons enable animals to detect environmental changes and avoid harm. An intriguing open question concerns how the various attributes of sensory neurons arise in development.

Fracture Healing Is Delayed In The Absence Of Gasdermin-Interleukin-1 Signaling, Kai Sun, Chun Wang, Jianqiu Xiao, Michael D. Brodt, Luorongxin Yuan, Tong Yang, Yael Alippe, Huimin Hu, Dingjun Hao, Yousef Abu-Amer, Matthew J. Silva, Jie Shen, Gabriel Mbalaviele

Open Access Publications

Amino-terminal fragments from proteolytically cleaved gasdermins (GSDMs) form plasma membrane pores that enable the secretion of interleukin-1β (IL-1β) and IL-18. Excessive GSDM-mediated pore formation can compromise the integrity of the plasma membrane thereby causing the lytic inflammatory cell death, pyroptosis. We found that GSDMD and GSDME were the only GSDMs that were readily expressed in bone microenvironment. Therefore, we tested the hypothesis that GSDMD and GSDME are implicated in fracture healing owing to their role in the obligatory inflammatory response following injury. We found that bone callus volume and biomechanical properties of injured bones were significantly reduced in mice lacking …

Targeting Etosis By Mir-155 Inhibition Mitigates Mixed Granulocytic Asthmatic Lung Inflammation, Ji Young Kim, Patrick Stevens, Manjula Karpurapu, Hyunwook Lee, Joshua A Englert, Pearlly Yan, Tae Jin Lee, Navjot Pabla, Maciej Pietrzak, Gye Young Park, John W Christman, Sangwoon Chung

Faculty, Staff and Student Publications

Asthma is phenotypically heterogeneous with several distinctive pathological mechanistic pathways. Previous studies indicate that neutrophilic asthma has a poor response to standard asthma treatments comprising inhaled corticosteroids. Therefore, it is important to identify critical factors that contribute to increased numbers of neutrophils in asthma patients whose symptoms are poorly controlled by conventional therapy. Leukocytes release chromatin fibers, referred to as extracellular traps (ETs) consisting of double-stranded (ds) DNA, histones, and granule contents. Excessive components of ETs contribute to the pathophysiology of asthma; however, it is unclear how ETs drive asthma phenotypes and whether they could be a potential therapeutic target. …

Pathogenic Tau Accelerates Aging-Associated Activation Of Transposable Elements In The Mouse Central Nervous System, Paulino Ramirez, Gabrielle Zuniga, Wenyan Sun, Adrian Beckmann, Elizabeth Ochoa, Sarah L Devos, Bradley Hyman, Gabriel Chiu, Ethan R Roy, Wei Cao, Miranda Orr, Virginie Buggia-Prevot, William J Ray, Bess Frost

Faculty, Staff and Student Publications

Transposable elements comprise almost half of the mammalian genome. A growing body of evidence suggests that transposable element dysregulation accompanies brain aging and neurodegenerative disorders, and that transposable element activation is neurotoxic. Recent studies have identified links between pathogenic forms of tau, a protein that accumulates in Alzheimer's disease and related "tauopathies," and transposable element-induced neurotoxicity. Starting with transcriptomic analyses, we find that age- and tau-induced transposable element activation occurs in the mouse brain. Among transposable elements that are activated at the RNA level in the context of brain aging and tauopathy, we find that the endogenous retrovirus (ERV) class …

Genetic Studies On Mammalian Dna Methyltransferases, Jiameng Dan, Taiping Chen

Faculty, Staff and Student Publications

Cytosine methylation at the C5-position-generating 5-methylcytosine (5mC)-is a DNA modification found in many eukaryotic organisms, including fungi, plants, invertebrates, and vertebrates, albeit its levels vary greatly in different organisms. In mammals, cytosine methylation occurs predominantly in the context of CpG dinucleotides, with the majority (60-80%) of CpG sites in their genomes being methylated. DNA methylation plays crucial roles in the regulation of chromatin structure and gene expression and is essential for mammalian development. Aberrant changes in DNA methylation and genetic alterations in enzymes and regulators involved in DNA methylation are associated with various human diseases, including cancer and developmental disorders. …