Neurosciences Commons^™

Loss Of Pleasure (Anhedonia): A Sex-Dependent, Cross-Species Consequence Of Unpredictable Signals To The Perinatal Brain, Anna M. Zhou, Madison R. Tetzlaff, Laura M. Glynn, Curt A. Sandman, Hal S. Stern, Tallie Z. Baram, Elysia Poggi Davis

Psychology Faculty Articles and Research

Reward seeking is an essential component of human behavior. Anhedonia (reduced motivation for and pleasure in reward) is a core feature of several mental illnesses. Early life adversity associates with later impairments in reward behaviors and related psychopathology; however, specific aspects of early adversity that lead to disrupted reward behaviors are unknown. Capitalizing on evidence that unpredictable signals to the developing brain constitute adversity and influence neurodevelopment, we examined whether exposure to perinatal unpredictable maternal signals associated with diminished reward responsivity, and probed causality using experiments in mice. We analyzed a longitudinal human study (N=158 mother/child dyads) and a …

Empowering Women: Understanding Neurological Changes In The Aging Brain, Joy Mckenzie

InnovateHER Meeting 2026

Women tend to have more neurological changes than men as they age starting in their mid-30s (Mosconi, 2024). While aging is a natural process, the neurological changes can impact a woman’s personal and professional quality of life (Faubion et al., 2023; Gravini, 2023). For years, women’s neurological symptoms have been ignored by being told that their experiences are normal and just a part of life (Haver, 2025). That narrative is starting to shift with the increased awareness of changes specific to women. There are resources to assess cognitive changes such as memory, processing speed, and word finding and strategies to …

Birth Control Use Alters Memory For A Stressful Experience, Julia N. Gross, Kristie Payment, Boyd R. Rorabaugh, Phillip R. Zoladz

Aurora

Hormonal birth control methods are widely used; however, some users suffer considerable side effects. Previous research suggests oral contraceptive users exhibit a blunted cortisol response to psychosocial stressors and alterations in emotional memory, including differential recall of emotional images and details of emotional stories. However, no studies have examined how birth control influences memory for a stressful experience.

The present study analyzes data previously collected from female undergraduate students. In this study, participants reported contraceptive use, then underwent a modified version of the Trier Social Stress Test (TSST) or the friendly-TSST (f-TSST). The TSST required participants to deliver a ten-minute, …

Improving Anesthesia Provider Confidence In The Identification, Management, And Treatment Of Postoperative Delirium, Brittany M. Whistle, Charles Dustin Phelps

Scholars Week

Purpose: Postoperative Delirium (POD) is a potentially devastating complication of anesthesia that is poorly understood by clinical staff leading to poor outcomes for surgical patients. This study is meant to determine if a focused knowledge presentation accompanied by visual aids could increase anesthesia providers confidence in identifying, diagnosing, and treating Postoperative Delirium.

Methodology: Utilizing a statistical model to analyze respondents results on a standardized test administered before and after an informational presentation with visual aids on the topic of Postoperative Delirium.

Results: Results indicated a statistically significant difference between pretest and posttest scores, with a p-value of .002, t(11) = …

The Role Of Top-Down Appetite Self-Regulation In The Development Of Healthy Eating Behaviors Among Children: A Narrative Review And Socialization Framework, David J Bridgett, Sheryl O Hughes, Matthew Broussard, Daniela Mccourt, Christina M Croce, Jennifer O Fisher

Faculty, Staff and Students Publications

Appetite self-regulation (ASR) among children is thought to have a fundamental role in shaping the development of healthy eating behaviors, dietary intake, and growth during childhood. Parallel to developmental frameworks for understanding "general" self-regulation among children, ASR has been described as involving children's use of "top-down" cognitive processes to moderate "bottom-up" biological drives around food approach and avoidance in the interest of achieving desired eating behaviors or outcomes. Whereas bottom-up ASR processes during early childhood are well characterized, particularly in the context of dysregulation and obesity risk, the role of top-down ASR processes in the development of healthy eating behaviors …

Investigating Tau Pathology In The Retina And Anterior Segment Structures Of The Eye In A 3-Nitropropionic Acid–Induced Tauopathy Mouse Model, Mohamed Sayed Ahmed Abdel-Kader Qasem

Theses and Dissertations

Background and Objectives: Alzheimer's disease, the most prevalent neurodegenerative disorder in older adults, is characterized by accumulation of hyperphosphorylated tau and amyloid-beta (Aβ) plaques in the central nervous system. Given the retina's shared embryological origin with the brain, its direct neural connectivity via the optic nerve, and similarities in vasculature and age-related degeneration patterns, retinal pathology may serve as an early, non-invasive biomarker for Alzheimer's disease. This study employed 3-nitropropionic acid (3NP) as a pathway-specific tauopathy model driven by mitochondrial dysfunction. The study particularly aimed to investigate whether retinal and corneal tau pathology reflects underlying tau-related neurodegeneration triggered by …

Neonatal Striatal Volume Is Associated With Infant Anhedonia, Melissa Nevarez-Brewster, Catherine H. Demers, Jessica L. Irwin, Laura M. Glynn, Martin A. Styner, Mercedes Hoeflich Haase, M. Camille Hoffman, Diego A. Pizzagalli, Benjamin L. Hankin, Elysia Poggi Davis

Psychology Faculty Articles and Research

Anhedonia is increasingly recognized as a transdiagnostic risk factor for psychopathology. New evidence demonstrates that anhedonia is present in infancy and early childhood. Structural variability in striatal regions involved in reward processing and pleasure seeking is concurrently linked to anhedonia, yet few studies have examined whether striatal differences presage anhedonia, and none have examined prospective associations before middle childhood. The present study examined whether neuroanatomical markers that confer risk for anhedonia can be detected as early as the neonatal period. Specifically, we tested whether the volume of striatal regions in neonates predicted the emergence of infant anhedonic behaviors at six …

Sensory Neuron-Expressed Fgf13 Controls Nociceptive Signaling In Diabetic Neuropathy Models, Aditya K Singh, Matteo Bernabucci, Nolan M Dvorak, Zahra Haghighijoo, Jessica Di Re, Nana A Goode, Feni K Kadakia, Laura A Maile, Olumarotimi O Folorunso, Paul A Wadsworth, Cynthia M Tapia, Pingyuan Wang, Jigong Wang, Haiying Chen, Yu Xue, Jully Singh, Kali Hankerd, Isaac J Gamez, Makenna Kager, Vincent Truong, Patrick Walsh, Stephanie I Shiers, Nishka Kuttanna, Hanyue Liao, Margherita Marchi, Erika Salvi, Ilaria D'Amato, Daniela D'Amico, Parsa Arman, Catharina G Faber, Rayaz A Malik, Marina De Tommaso, Dan Ziegler, Krishna Rajarathnam, Thomas A Green, Peter M Grace, Matthew R Sapio, Michael J Iadarola, Gregory D Cuny, Diana S Chow, Giuseppe Lauria Pinter, Steve Davidson, Dustin P Green, Jun-Ho La, Jin Mo Chung, Jia Zhou, Theodore J Price, Elizabeth Salisbury, Subo Yuan, Fernanda Laezza

Faculty, Staff and Student Publications

Nociception involves complex signaling, yet intrinsic mechanisms bidirectionally regulating this process remain unexplored. Here, we show that the fibroblast growth factor 13 (FGF13)/Nav1.7 protein-protein interaction (PPI) complex bidirectionally modulates nociception, and that the FGF13/Nav1.7 ratio is upregulated in type 2 diabetic neuropathy (T2DN). PW164, an FGF13/Nav1.7 channel C-terminal tail domain (CTD) PPI interface inhibitor, which reduces complex assembly, selectively suppressed Na+ currents sensitized by capsaicin-induced activation of TRPV1 channels in human induced pluripotent stem cell-derived (hIPSC-derived) sensory neurons and inhibited mechanical and thermal hyperalgesia in mice. FGF13 silencing mimics PW164 activity in culture and in vivo. Conversely, ZL192, an FGF13 …

Beyond The Genome: The Racialized Exposome, Flourishing, And Stress Biology In African Americans, A Non-Exhaustive Review, Enye Washington

University Honors Theses

Racial health disparities remain an enduring challenge in the United States, disproportionately impacting African American communities through higher rates of chronic disease and premature mortality. This non-exhaustive literature explores how the racialized exposome - a term denoting the totality of social, environmental, and structural stressors rooted in systemic racism - biologically embeds itself via stress-responsive pathways. Specifically, it examines the interaction between racial stress, flourishing, and key biological markers, including allostatic load and telomere length, considering the gut-brain axis. The review highlights robust evidence that chronic exposure to racial discrimination and structural adversity contributes to multisystem dysregulation and accelerated cellular …

The Effect Of Birthweight And Gestational Age On Cognitive Function In Midlife: The Bogalusa Heart Study, Eunsun Gill, David J Libon, Soo Jung Kang, Ileana De Anda-Duran, Lydia A Bazzano, Wei Chen, Camilo Fernandez-Alonso, Emily W Harville

Rowan-Virtua School of Osteopathic Medicine Departmental Research

BACKGROUND: Although the relationships between birthweight, gestational age (GA), and cognitive function (CF) before midlife have been demonstrated, the relationships after midlife and potential racial disparities remain inconclusive. This study examined the association between birthweight, GA, and midlife CF stratified by race.

METHOD: 1,032 subjects from the Bogalusa Heart Study (67% Whites, 33% Blacks, mean age 48.1 ± 5.3 years) were studied. Cognition was assessed with tests measuring verbal episodic memory, working memory, attention, graphomotor information processing speed, and global CF. Each test was standardized by sex and age, then averaged. The global CF was computed by averaging all cognitive …

The Small Gtpase Rap1 In Pomc Neurons Regulates Leptin Actions And Glucose Metabolism, Kentaro Kaneko, Weisheng Lu, Yong Xu, Alexei Morozov, Makoto Fukuda

Faculty, Staff and Students Publications

The hypothalamic leptin-proopiomelanocortin (POMC) pathway is critical for regulating metabolism. POMC neurons in the arcuate nucleus respond to leptin and play a pivotal role in mediating energy and glucose balance. However, during diet-induced obesity (DIO), these neurons often develop resistance to exogenous leptin. Recently, the small GTPase Rap1 has been implicated as an inhibitor of neuronal leptin signaling; however, its specific role within POMC neurons remains unexplored. We generated tamoxifen-inducible, POMC neuron-specific Rap1 knockout mice to selectively delete both Rap1a and Rap1b isoforms in POMC neurons. By analyzing these mice through metabolic phenotyping, immunohistochemistry, and biochemical assays, we show that …

The Impact Of An Iron-Rich Diet On Fatigue In Menstruating Women With Non-Anemic Iron Deficiency, Meagan Seraydar, Lauren Latimer, Sam Miragliatto

Department of Nutrition Student Projects

Fatigue without diagnosed anemia is prevalent in menstruating women, with iron deficiency being a potential contributor. While iron supplementation is a standard intervention, dietary sources of iron may offer a sustainable alternative. This study aims to assess the impact of an iron-rich diet on fatigue levels in menstruating women. A 12-week randomized controlled trial (RCT) will be conducted, assigning participants to either an iron-rich diet group or a control group following their usual diet without specific iron recommendations. Fatigue will be measured using the Fatigue Severity Scale (FSS) at baseline, six weeks, and twelve weeks, alongside iron status biomarkers, including …

Associations Between B Vitamin Interactions With Polyunsaturated Fatty Acids And Cognitive Function Among Cognitively Healthy Older People As Modified By Amyloid Status And Sex, Chuliang Zhao, Karen A. Abbott, Chinedu Momoh, Geraint Price, Oliver J. K. Robinson, Sujin Kang, Celeste A. De Jager Loots

Brain and Mind Institute

Background/Objectives: Nutrients such as vitamin B12, folate (B9), and polyunsaturated fatty acids (PUFAs) may independently influence cognitive health, but their combined effects and interactions remain unclear. This study aims to investigate the effects of B12, folate, and PUFAs, including their interactions, on cognitive function in cognitively healthy older adults, considering effect modification by sex and amyloid-beta status.

Methods: A cross-sectional analysis was conducted using data from 321 participants aged 60–85 y enrolled in the UK CHARIOT–PRO SubStudy. Dietary intake was assessed using the Scottish Collaborative Group Food Frequency Questionnaire, and cognitive performance was measured via the Repeatable Battery …

Microglial Disruption In Young Mice With Early Chronic Exposure To Lead, Christina Sobin, Mayra Flores Montoya, Natali Parisi, Tanner Schaub, Miguel Cervantes, Rodrigo Armijos

Departmental Papers (PH)

The mechanisms by which early chronic lead (Pb) exposure alters brain development have not been identified. We examined neuroimmune system effects in C57BL/6J mice with Pb exposure, including levels that may be common among children in lower socioeconomic income environments. Pups were exposed via dams’ drinking water from birth to post-natal day 28 to low, high or no Pb conditions. We compared gene expression of neuroinflammatory markers (study 1); and microglial mean cell body volume and mean cell body number in dentate gyrus, and dentate gyrus volume (study 2). Blood Pb levels in exposed animals at sacrifice (post-natal day 28) …

Wernicke-Korsakoff Syndrome: A Current Perspective, Astrid-Ines Foamkom, Maria Sophia Zaraspe Malbas, Kory D. Punch, Victor A. Bob-Yellowe, Allison J. Mcadams, Julia Paz, Karina Zamora, Kelsey Baker, Ihsan Salloum, Ney Alliey-Rodriguez

Research Symposium

Background: Wernicke-Korsakoff syndrome (WKS) is a debilitating neuropsychological condition characterized by the profound loss of thiamine (vitamin B1). The neuropsychological presentation of WKS has been increasingly refined since its discovery in the nineteenth century, leading to a more robust understanding of the condition. In general, it has been shown that WKS causes differ amongst individuals but the main causes for the condition include chronic alcoholism, immunodeficiency, genetic disorders, malnutrition, drug-induced thiamine deficiency, and hyperemesis gravidarum. However, it remains unclear how demographic, environmental, and ethnic differences may influence WKS etiology and severity. Here, we sought to conduct a systematic review of …

Altered Thermal Preference By Preoptic Estrogen Receptor Alpha Neurons In Postpartum Females, Nan Zhang, Meng Yu, Qianru Zhao, Bing Feng, Yue Deng, Jonathan C Bean, Qingzhuo Liu, Benjamin P Eappen, Yang He, Kristine M Conde, Hailan Liu, Yongjie Yang, Longlong Tu, Mengjie Wang, Yongxiang Li, Na Yin, Hesong Liu, Junying Han, Darah Ave Threat, Nathan Xu, Taylor Smiley, Pingwen Xu, Lulu Chen, Tianshu Zeng, Yanlin He, Chunmei Wang

Faculty, Staff and Students Publications

OBJECTIVE: This study aims to investigate how reproductive experience (RE) alters thermal preference and thermoregulation in female mice, with a focus on estrogen receptor alpha (ERα)-expressing neurons in the preoptic area (POA).

METHODS: Thermal preference and body temperature were measured in female mice with and without RE, and virgin female mice with selective deletion of ERα from the POA (ERα

RESULTS: We showed that female mice prefer a cooler environment starting from late pregnancy and persisting long term postpartum. Female mice with RE (>4 weeks post-weaning) displayed lower body temperature and a lower thermal preferred temperature, and lost preference …

Red Meat Consumption And Hypertension: An Updated Review, Tara S Allen, Michael Najem, Alexis C Wood, Danielle J Lee, Lorena S Pacheco, Lori B Daniels, Matthew A Allison

Faculty, Staff and Students Publications

PURPOSE OF REVIEW: Hypertension (HTN) is a major risk factor for cardiovascular diseases (CVD). The global prevalence of HTN and related CVD mortality continues to rise. The development of HTN is influenced by genetic predisposition and modifiable risk factors, including diet. One area of ongoing debate is the relationship between red meat consumption and risk of HTN.

RECENT FINDINGS: Processed red meat has become increasingly implicated in the pathogenesis and morbidity of HTN, though randomized control trials comparing HTN-related outcomes associated with red meat subtypes have yielded heterogenous results. This review summarizes the existing relevant literature and highlights the methodological …

The Global Epidemiology And Health Burden Of The Autism Spectrum: Findings From The Global Burden Of Disease Study 2021, Global Burden Of Disease Study 2021 Autism Spectrum Collaborators, Lourdes Bernadette Tanchanco, Angel Belle Dy

Ateneo School of Medicine and Public Health Publications

Background

High-quality estimates of the epidemiology of the autism spectrum and the health needs of autistic people are necessary for service planners and resource allocators. Here we present the global prevalence and health burden of autism spectrum disorder from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 following improvements to the epidemiological data and burden estimation methods.

Methods

For GBD 2021, a systematic literature review involving searches in PubMed, Embase, PsycINFO, the Global Health Data Exchange, and consultation with experts identified data on the epidemiology of autism spectrum disorder. Eligible data were used to estimate prevalence …

Molecular Modification Of Queen Bee Acid And 10-Hydroxydecanoic Acid With Specific Tripeptides: Rational Design, Organic Synthesis, And Assessment For Prohealing And Antimicrobial Hydrogel Properties, Song Hong, Sachin B. Baravkar, Yan Lu, Abdul Razak Masoud, Qi Zhao, Weilie Zhou

School of Medicine Faculty Publications

Royal jelly and medical grade honey are traditionally used in treating wounds and infections, although their effectiveness is often variable and insufficient. To overcome their limitations, we created novel amphiphiles by modifying the main reparative and antimicrobial components, queen bee acid (hda) and 10-hydroxyl-decanoic acid (hdaa), through peptide bonding with specific tripeptides. Our molecular design incorporated amphiphile targets as being biocompatible in wound healing, biodegradable, non-toxic, hydrogelable, prohealing, and antimicrobial. The amphiphilic molecules were designed in a hda(hdaa)-aa1-aa2-aa3 structural model with rational selection criteria for each moiety, prepared via Rink/Fmoc-tBu-based solid-phase peptide synthesis, and structurally verified by NMR and LC–MS/MS. …

Sex-Specific Astrocyte Regulation Of Spinal Motor Circuits By Nkx61, Navish A Bosquez Huerta, Zhung-Fu Lee, Eun-Ah Christine Song, Junsung Woo, Yi-Ting Cheng, Debosmita Sardar, Ozlem Sert, Ehson Maleki, Kwanha Yu, Ekin Su Akdemir, Kaitlyn Sanchez, Juyeon Jo, Matthew N Rasband, Hyun Kyoung Lee, Akdes Serin Harmanci, Benjamin Deneen

Faculty, Staff and Students Publications

Astrocytes exhibit diverse cellular and molecular properties across the central nervous system (CNS). Recent studies identified region-specific transcription factors (TF) that oversee these diverse properties; how sex differences intersect with region-specific transcriptional programs to regulate astrocyte function is unknown. Here, we show that the TF Nkx6.1 is specifically expressed in ventral astrocytes of the spinal cord and that its deletion results in sex-specific effects on astrocyte morphology. Astrocytes from males exhibit enhanced morphological complexity, accompanied by increased motor function and cholinergic synapses. In contrast, female astrocytes exhibit reduced complexity and no changes in motor function. Mechanistically, we found that Nkx6.1 …

The Adiponectin-Pparγ Axis In Hepatic Stellate Cells Regulates Liver Fibrosis, Shangang Zhao, Qingzhang Zhu, Wang-Hsin Lee, Jan-Bernd Funcke, Zhuzhen Zhang, May-Yun Wang, Qian Lin, Bianca Field, Xue-Nan Sun, Guannan Li, Mbolle Ekane, Toshiharu Onodera, Na Li, Yi Zhu, Christine M Kusminski, Terry D Hinds, Philipp E Scherer

Faculty, Staff and Students Publications

Hepatic stellate cells (HSCs) are key drivers of local fibrosis. Adiponectin, conventionally thought of as an adipokine, is also expressed in quiescent HSCs. However, the impact of its local expression on the progression of liver fibrosis remains unclear. We recently generated a transgenic mouse line (Lrat-rtTA) that expresses the doxycycline-responsive transcriptional activator rtTA under the control of the HSC-specific lecithin retinol acyltransferase (Lrat) promoter, which enables us to specifically and inducibly overexpress or eliminate genes in these cells. The inducible elimination of HSCs protects mice from methionine/choline-deficient (MCD) diet-induced liver fibrosis, confirming their causal involvement in fibrosis development. We generated …

The Quic-Sp: A Spanish Language Tool Assessing Unpredictability In Early Life Is Linked To Physical And Mental Health, Sabrina R. Liu, Natasha A. Bailey, Sara Romero-González, Amy Moors, Belinda Campos, Elysia P. Davis, Laura M. Glynn

Psychology Faculty Articles and Research

Accumulating evidence indicates that unpredictable signals in early life represent a unique form of adverse childhood experiences (ACEs) associated with disrupted neurodevelopmental trajectories in children and adolescents. The Questionnaire of Unpredictability in Childhood (QUIC) was developed to assess early life unpredictability, encompassing social, emotional, and physical unpredictability in a child’s environment, and has been validated in three independent cohorts. However, the importance of identifying ACEs in diverse populations, including non-English speaking groups, necessitates translation of the QUIC. The current study aims to translate and validate a Spanish language version of the QUIC (QUIC-SP) and assess its associations with mental and …

Sex Differences In Response To Diet Enriched With Glutathione Precursors In The Aging Heart, Aude Angelini, Grecia Garcia Marquez, Anna Malovannaya, Marta L Fiorotto, Alexander Saltzman, Antrix Jain, Joann Trial, George E Taffet, Katarzyna A Cieslik

Faculty, Staff and Students Publications

Common features of the aging heart are dysregulated metabolism, inflammation, and fibrosis. Elevated oxidative stress is another hallmark of cardiac aging that can exacerbate each of these conditions. We hypothesize that by increasing natural antioxidant levels (glutathione), we will improve cardiac function. Twenty-one-month-old mice were fed glycine and N-acetyl cysteine (GlyNAC; glutathione precursors)-supplemented or control diets for 12 weeks. Heart function was monitored longitudinally, and the exercise performance was determined at the end of the study. We found that the GlyNAC diet was beneficial for old male but not old female mice, leading to an increase of Ndufb8 expression (a …

Weighted Family History Density Of Substance Use: Influence On Participant Substance Use Onset, Escalation, And Duration, Carleigh A. Litteral

Theses and Dissertations--Psychology

Substance use disorders impose a staggering toll on the United States (U.S.), straining healthcare systems, destabilizing communities, and profoundly impacting both individuals and families. Approximately one in six Americans aged 12 and older had a past-year substance use disorder in 2022 (Key Substance Use, 2022), and nearly one-third of adults experience a substance use disorder in their lifetime (Wu, 2010), contributing to an economic burden exceeding $400 billion annually (National Drug Threat Assessment, 2011). Family history of substance use disorders is a key predictor of vulnerability, with individuals who have affected relatives being 2–8 times more …

Dual Inhibitor Of Mdm2 And Nfat1 For Experimental Therapy Of Breast Cancer: In Vitro And In Vivo Anticancer Activities And Newly Discovered Effects On Cancer Metabolic Pathways, Wei Wang, Marlene Aguilar, Sayantap Datta, Abigail Alley, Meheret Tadesse, Xinshi Wang, Xia Gao, Ruiwen Zhang

Faculty, Staff and Students Publications

INTRODUCTION: The oncogene MDM2 has garnered attention not only for its role in cancer as a negative regulator of the tumor suppressor p53 but also for its p53-independent oncogenic activities. MDM2 also involves metabolic reprogramming, such as serine metabolism, respiration, mitochondrial functions, the folate cycle, and redox balance. Traditional MDM2 inhibitors blocking the protein-protein binding between MDM2 and p53 have shown limited clinical success in various stages of clinical trials, most likely due to low efficacy, drug toxicity, and drug resistance, highlighting the need for a novel, p53-independent strategy to inhibit MDM2. The present study investigated the antitumor effects of …

Predictive Equation Derived From 6,497 Doubly Labelled Water Measurements Enables The Detection Of Erroneous Self-Reported Energy Intake, Rania Bajunaid, Chaoqun Niu, Catherine Hambly, Zongfang Liu, Yosuke Yamada, Heliodoro Aleman-Mateo, Liam J Anderson, Lenore Arab, Issad Baddou, Linda Bandini, Kweku Bedu-Addo, Ellen E Blaak, Carlijn V C Bouten, Soren Brage, Maciej S Buchowski, Nancy F Butte, Stefan G J A Camps, Regina Casper, Graeme L Close, Jamie A Cooper, Richard Cooper, Sai Krupa Das, Peter S W Davies, Prasangi Dabare, Lara R Dugas, Simon Eaton, Ulf Ekelund, Sonja Entringer, Terrence Forrester, Barry W Fudge, Melanie Gillingham, Annelies H Goris, Michael Gurven, Asmaa El Hamdouchi, Hinke H Haisma, Daniel Hoffman, Marije B Hoos, Sumei Hu, Noorjehan Joonas, Annemiek M Joosen, Peter Katzmarzyk, Misaka Kimura, William E Kraus, Wantanee Kriengsinyos, Rebecca Kuriyan, Robert F Kushner, Estelle V Lambert, Pulani Lanerolle, Christel L Larsson, William R Leonard, Nader Lessan, Marie Löf, Corby K Martin, Eric Matsiko, Anine C Medin, James C Morehen, James P Morton, Aviva Must, Marian L Neuhouser, Theresa A Nicklas, Christine D Nyström, Robert M Ojiambo, Kirsi H Pietiläinen, Yannis P Pitsiladis, Jacob Plange-Rhule, Guy Plasqui, Ross L Prentice, Susan B Racette, David A Raichlen, Eric Ravussin, Leanne M Redman, John J Reilly, Rebecca Reynolds, Susan B Roberts, Dulani Samaranayakem, Luis B Sardinha, Analiza M Silva, Anders M Sjödin, Marina Stamatiou, Eric Stice, Samuel S Urlacher, Ludo M Van Etten, Edgar G A H Van Mil, George Wilson, Jack A Yanovski, Tsukasa Yoshida, Xueying Zhang, Alexia J Murphy-Alford, Srishti Sinha, Cornelia U Loechl, Amy H Luke, Herman Pontzer, Jennifer Rood, Hiroyuki Sagayama, Dale A Schoeller, Klaas R Westerterp, William W Wong, John R Speakman

Faculty, Staff and Students Publications

Nutritional epidemiology aims to link dietary exposures to chronic disease, but the instruments for evaluating dietary intake are inaccurate. One way to identify unreliable data and the sources of errors is to compare estimated intakes with the total energy expenditure (TEE). In this study, we used the International Atomic Energy Agency Doubly Labeled Water Database to derive a predictive equation for TEE using 6,497 measures of TEE in individuals aged 4 to 96 years. The resultant regression equation predicts expected TEE from easily acquired variables, such as body weight, age and sex, with 95% predictive limits that can be used …

Orthogonal And Multiplexable Genetic Perturbations With An Engineered Prime Editor And A Diverse Rna Array, Qichen Yuan, Hongzhi Zeng, Tyler C Daniel, Qingzhuo Liu, Yongjie Yang, Emmanuel C Osikpa, Qiaochu Yang, Advaith Peddi, Liliana M Abramson, Boyang Zhang, Yong Xu, Xue Gao

Faculty, Staff and Students Publications

Programmable and modular systems capable of orthogonal genomic and transcriptomic perturbations are crucial for biological research and treating human genetic diseases. Here, we present the minimal versatile genetic perturbation technology (mvGPT), a flexible toolkit designed for simultaneous and orthogonal gene editing, activation, and repression in human cells. The mvGPT combines an engineered compact prime editor (PE), a fusion activator MS2-p65-HSF1 (MPH), and a drive-and-process multiplex array that produces RNAs tailored to different types of genetic perturbation. mvGPT can precisely edit human genome via PE coupled with a prime editing guide RNA and a nicking guide RNA, activate endogenous gene expression …

Urinary Metal Levels, Cognitive Test Performance, And Dementia In The Multi-Ethnic Study Of Atherosclerosis, Arce Domingo-Relloso, Katlyn E Mcgraw, Susan R Heckbert, Jose A Luchsinger, Kathrin Schilling, Ronald A Glabonjat, Irene Martinez-Morata, Melanie Mayer, Yongmei Liu, Alexis C Wood, Jeff Goldsmith, Kathleen M Hayden, Mohamad Habes, Ilya M Nasrallah, R Nick Bryan, Tanweer Rashid, Wendy S Post, Jerome I Rotter, Priya Palta, Linda Valeri, Timothy M Hughes, Ana Navas-Acien

Faculty, Staff and Students Publications

IMPORTANCE: Metals are established neurotoxicants, but evidence of their association with cognitive performance at low chronic exposure levels is limited.

OBJECTIVE: To investigate the association of urinary metal levels, individually and as a mixture, with cognitive tests and dementia diagnosis, including effect modification by apolipoprotein ε4 allele (APOE4).

DESIGN, SETTING, AND PARTICIPANTS: The multicenter prospective cohort Multi-Ethnic Study of Atherosclerosis (MESA) was started from July 2000 to August 2002, with follow-up through 2018. A total of 6303 MESA participants were included. Data analysis was performed from October 12, 2023, to June 13, 2024.

EXPOSURE: Urine samples were collected at baseline …

Association Of Common And Rare Variants With Alzheimer’S Disease In More Than 13,000 Diverse Individuals With Whole-Genome Sequencing From The Alzheimer’S Disease Sequencing Project, Wan-Ping Lee, Seung Hoan Choi, Margaret G Shea, Po-Liang Cheng, Beth A Dombroski, Achilleas N Pitsillides, Nancy L Heard-Costa, Hui Wang, Katia Bulekova, Amanda B Kuzma, Yuk Yee Leung, John J Farrell, Honghuang Lin, Brian W Kunkle, Adam Naj, Elizabeth E Blue, Frederick Nusetor, Dongyu Wang, Eric Boerwinkle, William S Bush, Xiaoling Zhang, Philip L De Jager, Josée Dupuis, Lindsay A Farrer, Myriam Fornage, Eden Martin, Margaret Pericak-Vance, Sudha Seshadri, Ellen M Wijsman, Li-San Wang, Alzheimer's Disease Sequencing Project;, Gerard D Schellenberg, Anita L Destefano, Jonathan L Haines, Gina M Peloso

Faculty, Staff and Student Publications

INTRODUCTION: Alzheimer's disease (AD) is a common disorder of the elderly that is both highly heritable and genetically heterogeneous.

METHODS: We investigated the association of AD with both common variants and aggregates of rare coding and non-coding variants in 13,371 individuals of diverse ancestry with whole genome sequencing (WGS) data.

RESULTS: Pooled-population analyses of all individuals identified genetic variants at apolipoprotein E (APOE) and BIN1 associated with AD (p < 5 × 10

DISCUSSION: We observed that complementary pooled-population and subgroup-specific analyses offered unique insights into the genetic architecture of AD.

HIGHLIGHTS: We determine the association of genetic variants with Alzheimer's disease (AD) using …

Chronic Β3-Ar Stimulation Activates Distinct Thermogenic Mechanisms In Brown And White Adipose Tissue And Improves Systemic Metabolism In Aged Mice, Duraipandy Natarajan, Bhuvana Plakkot, Kritika Tiwari, Shoba Ekambaram, Weidong Wang, Michael Rudolph, Mahmoud A Mohammad, Shaji K Chacko, Madhan Subramanian, Stefano Tarantini, Andriy Yabluchanskiy, Zoltan Ungvari, Anna Csiszar, Priya Balasubramanian

Faculty, Staff and Students Publications

Adipose thermogenesis has been actively investigated as a therapeutic target for improving metabolic dysfunction in obesity. However, its applicability to middle-aged and older populations, which bear the highest obesity prevalence in the United States (approximately 40%), remains uncertain due to age-related decline in thermogenic responses. In this study, we investigated the effects of chronic thermogenic stimulation using the β3-adrenergic (AR) agonist CL316,243 (CL) on systemic metabolism and adipose function in aged (18-month-old) C57BL/6JN mice. Sustained β3-AR treatment resulted in reduced fat mass, increased energy expenditure, increased fatty acid oxidation and mitochondrial activity in adipose depots, improved glucose homeostasis, and a …