Digital Commons Network^™

Preoperative Malnutrition Is Associated With Increased Postoperative Complications Following Lumbar Fusion: A Propensity-Matched Analysis, Ali Mehaidli, Muaaz Wajahath, Jad Lawand, Omar Abdalla, Lorenzo Deveza, Noah Hodson, Ryan J Berger, Kevin Taliaferro

Faculty, Staff and Students Publications

Background: Lumbar fusion (LF) is a common surgical intervention for degenerative spinal conditions but carries significant short- and long-term risks. Preoperative malnutrition, characterized by low serum albumin or leukocyte counts, impairs wound healing and increases susceptibility to infection, yet its influence on LF outcomes remains underexplored. This study evaluates the association between preoperative malnutrition and long-term postoperative outcomes following LF.

Methods: Adult patients undergoing LF between 2003 and 2023 were identified in the TriNetX US Collaborative Network. Malnutrition was defined as serum albumin < 3.5 g/dL or leukocyte count < 1,500/mm3 within 1 year preoperatively. A 1:1 propensity score match was performed for demographics, comorbidities, surgical approach, and body mass index (BMI), yielding two cohorts (n=20,693 each). Ninety-day and 5‑year postoperative outcomes were compared using hazard ratios (HRs) with 95% confidence intervals (CIs).

Results: Malnourished patients experienced significantly higher 90‑day rates of transfusion (8.4% vs. 4.5%; HR 1.87, 95% CI: …

Leveraging The Pedsnet Clinical Research Network And Electronic Health Record Data To Enhance Efficiency Of Trial Enrollment For A Rare Pediatric Rheumatic Disease, Pamela F Weiss, Levon Utidjian, Mitchell Maltenfort, Hanieh Razzaghi, Timothy G Brandon, Cassandra Muir, Cora Sears, Edward J Oberle, Jennifer Cooper, Kevin Baszis, Mary B Toth, Esi M Morgan, Christopher B Forrest

2020-Current year OA Pubs

BACKGROUND: We evaluated the PEDSnet clinical research network for study enrollment of juvenile spondyloarthritis, a rare rheumatic disease that includes enthesitis-related arthritis (ERA) and psoriatic arthritis (PsA). METHODS: An electronic health record (EHR)-based typology was developed by an interdisciplinary team to query EHR data for a spectrum of pediatric rheumatic diseases (2009–2023) from 8 PEDSnet centers. The prevalence, characteristics and drug exposures for juvenile spondyloarthritis was explored to gauge feasibility of leveraging the network for study enrollment. Next, the typology was adapted to identify subjects for a clinical trial; the efficiency of EHR typology query was compared to standard screening …

Human Chorionic Gonadotropin Decreases Cerebral Cystic Encephalomalacia And Parvalbumin Interneuron Degeneration In A Pro-Inflammatory Model Of Mouse Neonatal Hypoxia-Ischemia, Benjamin Miller, Alexander Crider, Bhooma Aravamuthan, Rafael Galindo

2020-Current year OA Pubs

Human chorionic gonadotropin (hCG) is an immunoregulatory and neurotrophic glycoprotein of potential clinical utility in the neonate at risk for cerebral injury. However, hCG has not been demonstrated to affect the pro-degenerative actions of inflammation in neonatal brain injury. Here we utilize a neonatal mouse model of mild hypoxia-ischemia (HI) combined with intraperitoneal administration of lipopolysaccharide (LPS) to evaluate the neuroprotective actions of hCG in the setting of systemic inflammation. Intraperitoneal treatment with hCG significantly decreased tissue loss and cystic degeneration in the hippocampus and cerebral cortex of term-equivalent neonatal mice exposed to LPS and HI. Noting that parvalbumin immunoreactive …

Sequential Platinum And Parp Inhibition Enhances Pd1 Immunotherapy Efficacy In Murine Brca2 Mutated Pancreatic Cancer, John C Mcvey, Max M Wattenberg, Heather Coho, Kayjana Infante, Kelly Markowitz, Devora Delman, Cynthia Clendenin, Emma E Furth, Rashmi Tondon, Ben Z Stanger, Robert H Vonderheide, Kim A Reiss, Gregory L Beatty

2020-Current year OA Pubs

Pancreatic ductal adenocarcinoma (PDAC) is a challenging malignancy to treat, but emerging evidence suggests that specific subtypes may respond more favorably to certain therapies. BRCA-mutated PDAC represents a distinct subtype that is particularly sensitive to DNA-damaging therapies. The current standard of care for advanced BRCA-mutated PDAC involves induction platinum-based chemotherapy followed by maintenance therapy with a poly (ADP-ribose) polymerase inhibitor (PARPi). However, the randomized phase III POLO trial, upon which this standard is based, did not demonstrate an improved overall survival in patients who received olaparib compared to those who received placebo, highlighting the need for new therapeutic approaches. Additionally, …

Red Bumps, Red Flags: A Case Series Of Four Neoplasms Masquerading As Inflamed Cutaneous Cysts, Jared Hensley, Smaran Marupudi, Kelly Maedo, Saba Suleman, Eric Sandrock

School of Medicine Publications

Red, inflamed cutaneous nodules are frequently diagnosed as epidermal inclusion cysts in both primary care and dermatology settings. However, several benign and malignant entities can closely mimic an inflamed cyst, leading to delayed diagnosis and suboptimal management. We present four patients who initially presented with erythematous nodules clinically suspected to be cysts; final histopathologic diagnoses included dermatofibroma, amelanotic melanoma, dermatofibrosarcoma protuberans, and undifferentiated pleomorphic sarcoma. For each case, we describe the clinical presentation, histopathology, and management. The presence of a central punctum and superficial mobility strongly favors an epidermal inclusion cyst. In contrast, the absence of a punctum, rapid growth, …

From Clicks To Clarity: Advanced Searching In Cinahl, Tracy Ashby, Jennifer Stockton

Library Class: Lunch & Learn

Take your CINAHL search to the next level. Learn practical techniques for combining Subject Headings, keywords, and filters to create strong, effective search strategies that support your evidence-based research.

Association, Affect, And Material Reading Practices Of Anna Laetitia Barbauld, Renee Harris

ABO: Interactive Journal for Women in the Arts, 1640–1830

At the end of the eighteenth century, reading practice was shifting from an embodied, affective exercise to a detached cognitive one. This essay examines how debates about truth and knowledge diverged along disciplinary and gender lines during this critical transition. The essay traces the influence of association psychology—particularly the theories of David Hartley and Joseph Priestley—on Romantic-era poets including Anna Laetitia Barbauld and Samuel Taylor Coleridge. Through Feminist Formalist Analysis attuned to affect and cognition, this essay demonstrates how Barbauld's poetic montages challenge the period's scientific discourse. Her "Inventory of the Furniture in Dr. Priestley's Study" and two "Hill of …

The Gendered Duality Of Coldness In The Portrayals Of Eliza Hayley, Francesca Blanch-Serrat

ABO: Interactive Journal for Women in the Arts, 1640–1830

In the eighteenth century, coldness was defined, on the one hand, in relation to the body and the senses (a body that is lacking in heat) and on the other, to emotion (an individual lacking in passion). It was linked to illness and disability (Turner, 2012), equated to death, seen as both a cause and effect of physical decline and older age, and used as a synonym for low libido and infertility (Toulalan, 2015). In contrast to these negative connotations, coldness was also regarded as a remedy to temper the passions and to ensure longevity (Yallop, 2015), and taking cold …

A Retrospective Review Of The Effects Of Patient Financial Assistance On Glycemic Control In Adults With Type 1 And Type 2 Diabetes Mellitus, Renee Kuess, Rachele Subik, Alexander Hill, Ron Carico Jr

Marshall Journal of Medicine

This study examined the effects of patient financial assistance on glycemic control in patients with type I and type II diabetes mellitus. Records for patients in our institution's endocrinology clinic who were enrolled in patient financial assistance were reviewed retrospectively. Patients were included if they were age 18 years or older, diagnosed with type I or II diabetes mellitus, enrolled in patient assistance through either manufacturer programs or our institution’s program, and had at least 6 months of glycemic data (i.e., A1c) prior to patient assistance enrollment and 6 months after, excluding 6 months of washout immediately after enrollment. A1c …

Rural Undergraduate Shadowing Program Bolsters Interest In Rural Healthcare Careers, Victoria Sanchez, Christie Zachary, April L. Vestal, Megan C. Govindan, A. Brianna Sheppard

Marshall Journal of Medicine

Background: Addressing rural healthcare provider shortages requires approaches to inspire and prepare future generations for rural health careers. The purpose of this evaluation was to assess the impact of an undergraduate rural shadowing pipeline program in advancement to graduate health professional school and future rural practice.

Methods: Baccalaureate-level students from multiple cohorts (2016-2021) who participated in the [University] Rural Undergraduate Shadowing in Healthcare Program completed surveys to assess their experience immediately following program completion. Descriptive statistics of end of program and follow-up surveys conducted 2023 were examined to evaluate the undergraduate pipeline program’s effectiveness.

Results: From 2016-2021, 26 students participated …

Unlocking Hope: Mirtazapine's Promise In Obsessive-Compulsive Disorder Treatment, Rebecca K. Hicks, Iram Kingson, Jordan Gaal, Suzanne Holroyd

Marshall Journal of Medicine

Obsessive-compulsive disorder (OCD) is a chronic and debilitating psychiatric condition characterized by intrusive thoughts (obsessions) and repetitive behaviors (compulsions). While selective serotonin reuptake inhibitors (SSRIs) and cognitive-behavioral therapy (CBT) are first-line treatments for OCD, a significant proportion of patients remain refractory to these interventions. Mirtazapine, an atypical antidepressant with unique pharmacological properties, has emerged as a potential adjunctive therapy for treatment-resistant OCD. This review synthesizes existing evidence regarding the efficacy and safety profile of mirtazapine in OCD management. We analyze clinical trials, observational studies, and case reports, distinguishing high- vs. low-quality evidence, and discuss mechanisms underlying mirtazapine's therapeutic effects. Additionally, …

An Enlarging Nodule On The Eyelid: A Case Of Apocrine Adenocarcinoma And Diagnostic Challenges, Kristen E. Bowman, Tyler Van Auken, Erin Reese, David Webb

Marshall Journal of Medicine

This is the case of a 49-year-old female who presented with a chronic, irritated lesion on her left upper eyelid. Following wide local excision, histopathological examination revealed a well-circumscribed lesion consistent with apocrine adenocarcinoma (AC). AC is a rare malignant tumor arising from apocrine sweat glands, typically found in the axillary and anogenital regions. Occasionally, it can present on the eyelid arising from specialized apocrine structures such as Moll’s glands.. AC of the eyelid is often misdiagnosed due to its clinical resemblance to benign conditions such as chalazion, potentially delaying appropriate treatment. Diagnosis relies heavily on histopathology and may be …

More Than A Healthcare Issue: Understanding The Breadth Of Occupational Burnout In Our Patients, Aliza Anderson*, Julia Maniccia*, Marc Moss

Marshall Journal of Medicine

Burnout is an occupation-related condition resulting from chronic workplace stress and is associated with significant psychological and physical morbidity. This commentary recognizes burnout as a public health concern across both healthcare and non-healthcare professions, illuminates key occupational risk and protective factors, reviews the biopsychosocial impacts of burnout, and argues for the integration of occupational health screening into clinical practice. A synthesis of the literature highlighted that existing research has focused primarily on healthcare occupations; however, emerging evidence demonstrates an elevated burnout risk in numerous non-healthcare occupations. Characterized by high job demands, limited autonomy, inadequate social support, and physically demanding labor, …

Symposium Day Reflection Paper - Burnout In Medicine: Understanding The Student & Resident Experience, Souraha Longo

Introduction to Public Health

A brief summary & reflection of a Symposium Day presentation (from a public health perspective).

Youth Violence, Cyberbullying, And Mental Health Among Adolescence: A Public Health Analysis Of Netflix’S “Adolescence”, Natepy Vann

Introduction to Public Health

It is a summary of a Netflix's series about British psychological crime thriller.

Reflection On ‘Adolescence’ And Mental Health, Souraha Longo

Introduction to Public Health

A brief summary & reflection of the Netflix Drama Adolescence (from a Public Health perspective).

Development Of Dirofilaria Immitis Adult Worms In Nsg Mice, Detection Of Parasite-Derived Microrna And Comparative Analysis Of Laboratory Isolates, Mohini Nakhale, Jessica A. Hess, Ellie Oliver, Nathan M. Ryan, Kirsten Mallon, Omair Sultan, Elinor Willis, Esha Banerjee, Enrico Radaelli, Charles-Antoine Assenmacher, Michael Povelones, Duncan Wells, Russ Morphew, Jennifer Willingham-Lane, Christine Henderson, John Harrington, Paul Mcveigh, David Abraham

Department of Surgery Faculty Papers

Global efforts to control heartworm disease are challenged by increasing drug resistance and inadequate early detection methods, which hinder the effective diagnosis and treatment of Dirofilaria immitis infection. This study presents an in vivo model for investigating D. immitis development and host-parasite interactions. The growth and migration of the D. immitis JYD-34 isolate were analyzed in immunodeficient NSG mice over 177 days, revealing parasite migration to the heart and lungs, which mirrors infection dynamics in the natural canine host. Pathophysiological examination of host tissues revealed early adult-stage worms elicited minimal inflammation. However, with chronicity, mild pulmonary hemosiderin accumulation was observed. …

Aadat-Driven Metabolic Control Of Malate And Coq10 Shapes Immune Evasion In Triple-Negative Breast Cancer, Megha Chatterjee, Franklin Gu, Susmita Samanta, Uttam Rasaily, Sai Manohar Thota, Dana Varghese, Yunping Qiu, Lynette Ewura Esi Fordwuo, Hugo Villanueva, Mary Kathryn Mckenna, Jun Hyoung Park, Weijie Zhang, Lin Tian, Liqun Yu, Badrajee Piyarathna, Yang Gao, Brian Wesley Simons, Sung Yun Jung, Balasubramanyam Karanam, Vasanta Putluri, Nagi Chandandeep, Nada Mohamed, Jaya Ruth Asirvatham, Deborah Jebakumar, Arundati Rao, Carolina Gutierrez, Angela R Omilian, Carl Morrison, Gokul M Das, Christine Ambrosone, Erin H Seeley, Benny Abraham Kaipparettu, Irwin J Kurland, Nagireddy Putluri, Ahmed Elkhanany, Andrew A Davis, Qian Zhu, Xiang H-F Zhang, Arun Sreekumar

Faculty, Staff and Students Publications

Compared to other subtypes of breast cancer, triple-negative breast cancers (TNBC) have fewer treatment options and exhibit a worse prognosis. Through integrated transcriptomic, metabolomic, immunohistochemical, spatial, and clinical analyses, we identify the mitochondrial enzyme, α-aminoadipate aminotransferase (AADAT) as a previously unrecognized metabolic immune checkpoint in TNBC. AADAT mRNA and protein were significantly upregulated in human TNBC, and high AADAT expression was associated with reduced intra-tumoral CD8+ T-cell density and inferior survival. Genetic silencing of AADAT in orthotopic murine TNBC models curtailed primary tumor growth and distant metastasis in a CD8+ T-cell–dependent manner, enhanced effector T-cell activation, and sensitized tumors to …

Novel R Shiny Tool For Survival Analysis With Time-Varying Covariate In Oncology Studies: Overcoming Biases And Enhancing Collaboration, Yimei Li, Yang Qiao, Fei Gao, Jordan Gauthier, Qiang Ed Zhang, Jenna Voutsinas, Wendy Leisenring, Ted Gooley, Corinne Summers, Alexandre Hirayama, Cameron Turtle, Rebecca Gardner, Jarcy Zee, Qian Vicky Wu

Wills Eye Hospital Papers

PURPOSE: Our study is motivated by evaluating the role of hematopoietic cell transplantation (HCT) after chimeric antigen receptor T-cell (CAR-T) therapy for ALL, a debated topic. Because patients may receive HCT at different times after CAR-T infusion or never, HCT post-CAR-T should be considered as a time-varying covariate (TVC).

METHODS: Standard Cox models and Kaplan-Meier (KM) curves (naïve method) assume that TVC status is known and fixed at baseline, which can yield biased estimates. Landmark analysis is a popular alternative but depends on a chosen landmark time. Time-dependent (TD) Cox model is better suited for TVC although visualizing survival curves …

High-Throughput Proteomic Profiling To Evaluate Differentiation Syndrome With Menin Inhibition, Miriam B Garcia, Bofei Wang, Irtiza Sheikh, Georgina El Hajjar, David Mccall, Cesar Nunez, Amber Gibson, Philip L Lorenzi, Ghayas C Issa, Branko Cuglievan, Hussein A Abbas

Faculty, Staff and Student Publications

High-throughput proteomic profiling provides a comprehensive analysis of systemic cancer effects and tumor microenvironment interactions. Characterizing soluble proteins driving inflammation in acute myeloid leukemia (AML) offers insight into inflammatory diseases like differentiation syndrome (DS) related to AML therapies like menin inhibitors. We present our application of NUcleic acid-Linked Immuno-Sandwich Assay (NULISA), a novel technology leveraging next-generation sequencing (NGS) for high-throughput, ultra-sensitive characterization of secreted inflammatory proteins in plasma or serum. Here we report its use to identify dynamic soluble protein changes during treatment and at the time of suspected DS in pediatric AML patients treated with the menin inhibitor revumenib …

Supercharging-Enhanced Ndia-Ms Enables Global Profiling Of Drug-Induced Proteome Solubility Shifts, Yun Xiong, Huimin Zhang, Lin Tan, Bo Wei, John N Weinstein, Philip L Lorenzi

Faculty, Staff and Student Publications

Mass spectrometry (MS) is indispensable for high-throughput quantitation of protein expression. But protein function is regulated by factors beyond abundance alone. Here, we evaluate two supercharging reagents, dimethyl sulfoxide (DMSO) and m-nitrobenzyl alcohol (mNBA), in narrow-window data-independent acquisition (nDIA)-MS. DMSO markedly enhances MS signal and protein identification, whereas mNBA primarily increases peptide identifications. Optimizating nDIA-MS with 3% DMSO boosts signal intensity by up to 56%, enabling identification of ~9,600 proteins from 1 µg HeLa digest in 15 min. Using this methodology, we quantify solubility and abundance changes in 8,694 proteins across three cell lines following short-term treatment with the proteasome …

Upper Hemisternotomy Vs. Full Sternotomy For Hemiarch And Proximal Aortic Replacement, Jeffrey A. Zucker, Vishal N. Shah, Joshua R. Chen, Christopher Pritting, Colin King, Jacqueline Mcgee, Megary Mccoy, Konstadinos A. Plestis

Department of Surgery Faculty Papers

Introduction: Hemiarch replacement with proximal aortic replacement is seldom performed via upper hemisternotomy (UHS). We report our surgical technique and postoperative outcomes in 11 patients who underwent UHS for hemiarch and proximal aortic replacement, compared with 15 patients who underwent the procedure via full sternotomy (FS).

Methods: A UHS was performed at the right third or fourth intercostal space. Cardiopulmonary bypass (CPB) was established via the distal ascending aorta or right axillary artery and right common femoral vein. After aortic cross-clamping (ACC), the heart was arrested with single-dose antegrade crystalloid cardioplegia. After proximal aortic replacement, hypothermic circulatory arrest (HCA) between …

Perceived Neighborhood Safety And Firearm Secure Storage: Findings From The 2024 Behavioral Risk Factor Surveillance System, Alexander Testa, Karyn Fu, Muhammed Ahmed, Daniel C Semenza, Dylan B Jackson, Sandra Mckay, Kyle T Ganson, Jason M Nagata

Faculty, Staff and Student Publications

Background: Secure firearm storage (i.e., keeping firearms locked and ammunition stored separately) is a means of reducing risks of suicide, unintentional injury, and homicide. While prior research has examined demographic and household factors associated with storage practices, less is known about how contextual factors, such as perceived neighborhood safety from crime, influence firearm storage behavior.

Methods: Data were from the 2024 Behavioral Risk Factor Surveillance System (BRFSS), a nationally coordinated, state-based survey administered by state health departments with technical and methodological support from the Centers for Disease Control and Prevention. Analyses were restricted to respondents in firearm-owning households from ten …

Factors Influencing Match Success In Integrated Vascular Surgery Residency Programs From 2019 To 2023, Antony A. Fuleihan, Melissa C. Xu, Scott H. Koeneman, Paul J. Dimuzio, Babak Abai, Michael Nooromid

Department of Surgery Faculty Papers

INTRODUCTION: Integrated vascular surgery residency (IVSR) programs have grown increasingly competitive. However, the factors influencing successful matching remain unclear. This study evaluates the impact of medical school and applicant characteristics on IVSR match outcomes.

METHODS: A list of ACGME-accredited IVSRs was obtained from the Society for Vascular Surgery, and resident data from the 2019-2023 match cycles were collected from publicly available sources. Applicant characteristics consisted of additional graduate degrees, Alpha Omega Alpha (AOA) status, and research productivity. Medical school characteristics consisted of ranking, research funding, vascular surgery interest group (VSIG) presence, and vascular surgery faculty size. Logistic regression models were …

New Inhibitors Of Neuronal Nitric Oxide Synthase For The Treatment Of Melanoma, Amardeep Awasthi, Anika Patel, Huiying Li, Koon Mook Kang, Christine D. Hardy, Anas Ansari, Raghad Nowar, Hasan Alhaddad, Md. Emtiaz Hasan, Sun Yang, Thomas L. Poulos, Richard B. Silverman

Pharmacy Faculty Articles and Research

In 2024, an estimated 100,640 new cases of invasive melanoma were diagnosed in the U.S., with 9290 deaths. Our previous studies revealed that neuronal nitric oxide synthase (nNOS) derived nitric oxide plays a critical role in melanoma progression, making nNOS inhibition a promising strategy. High structural similarity among NOS isoforms requires careful design of nNOS inhibitors to avoid off-target effects. Our previous lead, HH044, demonstrated potent antimelanoma activity but exhibited only moderate nNOS selectivity. Here, we utilized a structure-based approach to design nNOS inhibitors that promote interactions with human nNOS-specific residue His342. Compound 9 exhibited inhibition of both human ( …

Cool Under Pressure: Optimizing Skin Integrity With The Arctic Sun, Claire Little, Ariana Medrano, Zaria Duncan, Neyda Saravia

2025

No abstract provided.

Functional Genomic Analysis Of Non-Canonical Dna Regulatory Elements Of The Aryl Hydrocarbon Receptor, Shayan Shahriar, Tajhal D Patel, Manjula Nakka, Sandra L Grimm, Cristian Coarfa, Daniel A Gorelick

Faculty, Staff and Students Publications

The aryl hydrocarbon receptor (AHR) is a ligand-dependent transcription factor activated by environmental toxicants like halogenated and polycyclic aromatic hydrocarbons, which then binds to DNA and regulates gene expression. AHR is implicated in numerous physiological processes, including liver and immune function, cell cycle control, oncogenesis, and metabolism. Traditionally, AHR binds a consensus DNA sequence (GCGTG), the xenobiotic response element (XRE), recruits coregulators, and modulates gene expression. Yet, recent evidence suggests AHR can also regulate gene expression via a non-consensus sequence (GGGA), termed the non-consensus XRE (NC-XRE). The prevalence and functional significance of NC-XRE motifs in the genome have remained unclear. …

Beyond Bile Acids Synthesis: Metabolomics Profiling Highlights Extensive Metabolic Dysregulation And Treatment Response In Ctx, Monte A Del Monte, Jennifer Hanson, Penelope E Bonnen

Faculty, Staff and Students Publications

Background: Cerebrotendinous xanthomatosis (CTX) is an inherited metabolic disorder caused by variants in CYP27A1 leading to loss of sterol-27-hydroxylase activity. Sterol-27-hydroxylase generates two classes of bioactive signaling molecules: bile acids and oxysterols. The broader metabolic consequences resulting from perturbations in bile acid and oxysterol signaling and their reversibility with FDA-approved treatment chenodeoxycholic acid (CDCA), are not fully described.

Methods: To establish a comprehensive map of metabolic consequences of CTX, we performed large-scale, untargeted plasma metabolomics in a single subject with CTX, both before and after 6 months of CDCA therapy, and compared results with a reference cohort of over 1100 …

Functional Genomic Analysis Of Non-Canonical Dna Regulatory Elements Of The Aryl Hydrocarbon Receptor, Shayan Shahriar, Tajhal D Patel, Manjula Nakka, Sandra L Grimm, Cristian Coarfa, Daniel A Gorelick

Faculty, Staff and Students Publications

The aryl hydrocarbon receptor (AHR) is a ligand-dependent transcription factor activated by environmental toxicants like halogenated and polycyclic aromatic hydrocarbons, which then binds to DNA and regulates gene expression. AHR is implicated in numerous physiological processes, including liver and immune function, cell cycle control, oncogenesis, and metabolism. Traditionally, AHR binds a consensus DNA sequence (GCGTG), the xenobiotic response element (XRE), recruits coregulators, and modulates gene expression. Yet, recent evidence suggests AHR can also regulate gene expression via a non-consensus sequence (GGGA), termed the non-consensus XRE (NC-XRE). The prevalence and functional significance of NC-XRE motifs in the genome have remained unclear. …

Ubiquitous Low-Energy Rna Fluctuations And Energetic Coupling Measured By Chemical Probing, Edric K Choi, Ritwika Bose, David H Mathews, Anthony M Mustoe, Julius B Lucks

Faculty, Staff and Students Publications

RNA function is governed by RNA folding, but strategies for measuring RNA folding thermodynamics are limited, and fundamental questions such as the energy of base pair opening remain debated. Here we introduce Probing-Resolved Inference of Molecular Energetics (PRIME) to extract nucleotide-resolution RNA structural energetics from scalable chemical probing experiments. Applying PRIME to diverse RNAs, we find that RNA base pairs and tertiary interactions dynamically open with free energies of 0.5-3 kcal/mol, revealing that RNA nucleotides ubiquitously sample open conformations at biologically accessible energies. PRIME further resolves energetic coupling across RNAs, providing an energetic understanding of RNA structural dynamics and long-range …