Digital Commons Network^™

Biophysical Processes Of Morphogenesis In Lizard Lungs, Kaleb Hill, Aaron H. Griffing, Michael A. Palmer, Bezia Lemma, Aria S. Lupo, Tony Gamble, Natalia A. Shylo, Andrej Kosmrlj, Paul A. Trainor, Celeste M. Nelson

Biological Sciences Faculty Research and Publications

Background

The lungs of squamate reptiles (lizards and snakes) are highly diverse, exhibiting single chambers, multiple chambers, transitional forms with two to three chambers, along with a suite of other anatomical features, including finger-like epithelial projections into the body cavity known as diverticulae. During embryonic development of the simple, sac-like lungs of anoles, the epithelium is pushed through the openings of a pulmonary smooth muscle mesh by the forces of luminal fluid pressure. This process of stress ball morphogenesis generates the faveolar epithelium typical of squamate lungs.

Results

Here, we compared embryonic lung development in brown anoles, leopard geckos, and …

The Ai-Powered Learning Loop In Higher Education, Oualid Abidi, Vladimir Dzenopoljac, Aleksandra Dzenopoljac

All Works

Purpose – This study examines how generative AI tools affect business students’ academic performance by investigating whether flexible AI policies promote deeper learning, enhance self-efficacy and facilitate tacit knowledge acquisition in a Middle Eastern context, while ensuring efficiency and academic integrity. Design/methodology/approach – A qualitative, exploratory study observed 20 final-year business students in Kuwait during five in-class activities using generative AI tools. Semi-structured interviews complemented the researcher’s observations. Thematic analysis revealed patterns in benefits, challenges and learning processes, leading to the development of the AI-powered learning loop framework to explain academic performance outcomes. Findings – The study indicates that generative …

Catalytic Removal Of Synozol Blue Dye From Aqueous Solution Through Green Synthesized Iron Nps With H2o2: With Addition Of Ecosar And Biological Investigation, Rabiya Kousar, Zia Ul Haq Khan, Jingyu Sun, Sana Sabahat, Noor Samad Shah, Jibran Iqbal, Mahmood M.S. Abdullah, Rabia Naz, Zia Ullah Khan

All Works

This bioinspired study explores the fascinating realm of clean and green chemistry by unveiling the potential of FeO NPs fabricated by taking advantage of botanical extract obtained from the leaves of Justicia adhatoda as a reducing agent because it reduced Fe (II) to Fe (0). FeONPs have been fabricated successfully with distinctive structural and morphological features that have been characterized through multiple analytical techniques, like UV/Vis, FTIR, XRD, SEM, TEM, BET, and Zeta potential. The surface plasmonic resonance peak appeared at 268 nm, which was measured through the UV/Vis spectra of synthesized NPs. XRD analysis discovered the crystalline nature of …

Itrusst Consensus On Biophysical Safety For Transcranial Ultrasound Stimulation, Jean François Aubry, David Attali, Mark E. Schafer, Elsa Fouragnan, Charles F. Caskey, Robert Chen, Ghazaleh Darmani, Ellen J. Bubrick, Jérôme Sallet, Christopher R. Butler, Charlotte J. Stagg, Miriam C. Klein-Flügge, Seung Schik Yoo, Christy K. Holland, Bradley Treeby, Eleanor Martin, Lennart Verhagen, Kim Butts Pauly

School of Psychology

Transcranial ultrasound stimulation (TUS) is an emerging technology for non-invasive brain stimulation. The International Transcranial Ultrasonic Stimulation Safety and Standards consortium (ITRUSST) has established consensus on considerations for nonsignificant biophysical risk of TUS, drawing upon the literature and established regulations for biomedical devices. Here, we assume the application of TUS to individuals without contraindications, compromised thermoregulation, vascular vulnerabilities, or administered ultrasound contrast agents. In this context, we present a concise yet comprehensive set of levels for nonsignificant risks of TUS application. For mechanical effects, it is non-significant risk if the mechanical index (MI) or the mechanical index for transcranial application …

‘Earth System Engineers’ And The Cumulative Impact Of Organisms In Deep Time, Simon A. F. Darroch, Michelle M. Casey, Alison T. Cribb, Amanda E. Bates, Matthew E. Clapham, Dori L. Contreras, Matthew Craffey, Ivo A. P. Duijnstee, William Gearty, Nicholas J. Gotelli, Marcus J. Hamilton, Riley F. Hayes, Pincelli M. Hull, Daniel E. Ibarra, V. A. Korasidis, Jaemin Lee, Cindy V. Looy, Tyler R. Lyson, Benjamin Muddiman, Peter D. Roopnarine, Alex B. Shupinski, Felisa A. Smith, Alycia L. Stigall, Catalina P. Tomé, Katherine A. Turk, Amelia Villaseñor, Peter J. Wagner, Steve C. Wang, S. Kathleen Lyons

College of Life Sciences Faculty Papers

Understanding the role of humans as 'ecosystem engineers' requires a deep-time perspective rooted in evolutionary history and the fossil record. However, no conceptual framework exists for studying the rise of ecosystem engineering in deep time, requiring us to consider effects that fall outside the scope of traditional definitions. Here, we present a new framework applicable to both modern and ancient engineering-type effects. We propose a new term - 'Earth system engineering' - to describe biological processes that alter the structure and function of planetary spheres, and which combines core tenets of ecosystem engineering, niche construction, and legacy effects. We illustrate …

Fabrication Of Multimodal Anion Exchange Membrane For Chromatographic Purification Of Full Adeno-Associated Viral Capsids, Xiaolei Hao, Sumith Ranil Wickramasinghe, Xianghong Qian

Biomedical Engineering Faculty Publications and Presentations

A multi-modal anion exchange ligand 2-methyl-phenylimidazole has been successfully functionalized on highly porous electrospun regenerated cellulose membrane substrate for the separation of full and empty adeno-associated viral (AAV) capsids. The functionalized membrane has an average pore size of 0.5 mu m and exhibits both charge and hydrophobic functionality. The ligand is able to distinguish the subtle physio-chemical differences between the full and empty viral capsids. The multi-modal anion exchange membrane is able to separate the full capsids from affinity-captured mammalian AAV2 using both gradient and two-step elution methods with superior performance. A full capsid recovery of 72.9% at 85.3% purity …

Metabolic Flexibility As A Candidate Mechanism For The Development Of Postoperative Morbidity, Pietro Arina, John Whittle, Maciej R Kaczorek, Davide Ferrari, Nicholas Tetlow, Amy Dewar, Robert Stephens, Daniel Martin, S Ramani Moonesinghe, Evangelos B Mazomenos, Mervyn Singer

Peninsula Medical School

BACKGROUND: This study investigates the role of metabolic flexibility in determining perioperative outcomes. Metabolic flexibility, a key feature of metabolic health, is the ability to efficiently switch between different fuel sources (predominantly carbohydrates and fats) depending on energy demands and availability. Given the rapidly changing physiological conditions in the perioperative period, we hypothesized that good metabolic adaptability could mitigate postoperative complications. METHODS: We conducted a retrospective observational study utilizing a prospectively collected, single-center preoperative cardiopulmonary exercise testing (CPET) database of patients undergoing a range of major surgeries between 2012 and 2022. On day 3, patients were categorized into 3 groups …

Determining The Accumulation Potential Of Nanoplastics In Crops: An Investigation Of 14C-Labelled Polystyrene Nanoplastic Into Radishes, Nathaniel J. Clark, Astrid C. Fischer, Demelza Carne, George R. Littlejohn, Lee J. Durndell, Anne Plessis, Richard C. Thompson

School of Biological and Marine Sciences

The capacity of crops to accumulate nanoplastics has remained relatively unexplored largely due to analytical constraints. To address this challenge, the present study employed a radiolabelling approach to demonstrate, for the first time, that polystyrene nanoplastics (¹⁴C-PS NPs) accumulate and move into the edible tissues of radishes (Raphanus sativus). Radishes were exposed hydroponically for five days, with only their non-fleshy roots in contact with the ¹⁴C-PS NPs, while accumulation in the fleshy (edible) roots and shoots was subsequently measured. The radish roots retained nearly 5 % of the ¹⁴C-PS NPs from the exposure, either through accumulation …

Plastic Or Natural? The Impact Of Marine Debris On The Shell Preference Of A Terrestrial Hermit Crab, Robert Puschendorf, Pete Cotton, Mark Briffa

School of Biological and Marine Sciences

Plastic pollution is one of the main human-induced rapid environmental changes threatening marine organisms. Terrestrial hermit crabs, which inhabit coastal areas where litter accumulates, are increasingly documented using plastic debris as shells, and a recent study hypothesized that this shift may be an adaptive response. They suggested that ‘plastic shells’ may reduce transport costs, provide camouflage in a polluted environment, and may even be favoured by sexual selection. Our study is the first to quantify plastic shell use in a population, to examine shell preference and to test the hypothesis that plastic shells optimize the ratio of weight to volume. …

Potentially Toxic Metals, Anthropogenic Microfibres And Other Microplastics In Sediments From A Small, Urban Estuary (Plym, Southwest England), Kwong Ricky Li, Andrew Turner

School of Geography, Earth and Environmental Sciences

Anthropogenic microfibres (AMFs) and microplastics (MPs) are pervasive and ubiquitous environmental contaminants of growing concern. However, their study in geosolids, like sediments, is often conducted in the absence of other important geochemical and anthropogenic markers. In the present study, surface and subsurface sediments from the Plym Estuary, southwest England, have been analysed for AMFs and MPs along with organic matter (as loss on ignition; LOI), calcium, iron, manganese and potentially toxic metals (PTMs). The latter were heterogeneously distributed throughout the estuary because of multiple inputs and variations in sediment granulometry. AMFs were mainly constructed of cellulosic and petroleum-based polymers and …

Epigenetic And Genotoxic Effects Of Tritium In Marine Mussels: Comparing Waterborne And Metal-Associated Forms, Maria Florencia Ferreira, Andrew Turner, Mickaël Payet, Olivier Debellemaniere, Christian Grisolia, Veronique Malard, Michael N. Moore, Awadhesh N. Jha

School of Geography, Earth and Environmental Sciences

Tritium (³H), an isotope of hydrogen, is a by-product of the nuclear industry. Decommissioning and normal operations of nuclear facilities can generate tritiated stainless-steel particles (T-SSPs) that could be unintentionally released into the environment. Considering tritium's physicochemical properties and the proximity of nuclear facilities to water bodies, assessing the behaviour and potential effects of these particles in the aquatic environment is imperative. In the present study, marine mussels, Mytilus galloprovincialis, were exposed to: (a) hydrogenated, non-radioactive stainless-steel particles (H-SSPs) (10 mg L⁻¹) (b) T-SSPs (1 and 10 MBq L⁻¹) and (c) tritiated water (HTO) …

Perfluoroalkyl Substance Pollutants Disrupt Microglia Function And Trigger Transcriptional And Epigenomic Changes, Yating Cheng, Jian-Rong Li, Hangjin Yu, Shuang Li, Boranai Tychhon, Chao Cheng, Yi-Lan Weng

Faculty, Staff and Students Publications

Per- and polyfluoroalkyl substances (PFAS), commonly referred to as "forever chemicals", are widely utilized in various industries and consumer products worldwide. Their exposure has been associated with numerous diseases and malignancies, including neurodevelopmental and neurodegenerative disorders. However, the molecular mechanisms underlying PFAS-induced adverse effects on the central nervous system (CNS) remain poorly understood. In this study, we investigated the transcriptomic and epigenetic changes in microglia exposed to perfluorooctane sulfonate (PFOS), a prevalent PFAS compound. Our findings demonstrate that 24-hour PFOS exposure (25 and 50 µM) disrupts the microglial transcriptome and compromises their homeostatic state, marked by increased inflammation and impaired …

Sim And Learn: Simulation And Its Value In Neurology Education, Laveena Singla, Fariha Jamal, Anju Abu, Dana Ionel, Amtul Farheen

Faculty, Staff and Students Publications

Background: Simulation is a widely used health care education tool. Its use is increasing in acute neurologic conditions and has great potential to help trainees better perform procedures and enhance communication and professionalism.

Observations: This article describes the different neurologic simulations used as educational tools and the evidence that demonstrates their value. It also details the benefits afforded by simulations (eg, improved adherence to protocols, reduced door-to-needle time in stroke care) and areas of opportunity. It includes the use of virtual reality to allow trainees to interact with 3-dimensional models of the brain as well as augmented reality to view …

Hydrogen, Single-Carbon Compounds, And Thermal Regime In The Oceanic Ultramafic-Dominated Lithosphere: Insights From A Deep Borehole On The Atlantis Massif, Susan Q. Lang, C. Geoffrey Wheat, Kristin L. Dickerson, Mark K. Reagan, Ivan P. Savov, Jordyn A. Robare, William J. Brazelton, Johanna Suhonen, Oscar Cavazos, Andrew Mccaig, Peter Blum, Natsue Abe, Rémi Coltat, Jeremy R. Deans, Marguerite Godard, Barbara E. John, Frieder Klein, Rebecca Kuehn, Kuan Yu Lin, C. Johan Lissenberg, Haiyang Liu, Ethan L. Lopes, Toshio Nozaka, William Osborne, Andrew J. Parsons, Vamdev Pathak, Jessica Rodgers, Jeffrey S. Seewald, Kenneth W. Sims, Gordon Southam

School of Geography, Earth and Environmental Sciences

Water that flows through permeable ultramafic rocks produces high abundances of molecular hydrogen (H₂), methane (CH₄), and other small organic molecules. Such products can fuel life in the rocky subseafloor, be extracted for energy, and may have played a role in pre-biological chemical synthesis on early Earth or other planetary bodies. The International Ocean Discovery Program drilled a new 1268-m-deep borehole (U1601C) into serpentinized mantle with minor gabbroic rocks on the Atlantis Massif, ∼800-m north of the Lost City hydrothermal field (30°N, Mid-Atlantic Ridge). Measured temperatures of the disturbed borehole reached 91.3 °C, and equilibrated temperatures …

Characterizing Piezoelectric-Blended Polydimethylsiloxane For Use As A Mechanoelectrical Responsive Cell Culture Substrate, Alexis P. Applequist, Lance D. Cordes, Lais A. Ferreira, Kartik Balachandran

Biomedical Engineering Faculty Publications and Presentations

In this study, we developed a piezoelectric-polydimethylsiloxane (pz-PDMS) composite by blending poly(vinylidene fluoride-co-trifluoroethylene) (P(VDF-TrFE)) with PDMS to create a biocompatible, mechanoelectrical responsive material. The pz-PDMS was synthesized with varying piezoelectric concentrations (0%, 1%, 3%, and 5%) and characterized for visual properties, mechanical properties, mechanoelectrical sensitivity, and biocompatibility. Compression testing showed no significant change in mechanical strength with the addition of piezoelectric particles, while mechanolectrical sensitivity testing revealed a non-linear increase in voltage response, with 5% pz-PDMS producing the highest sensitivity. Fatigue testing demonstrated no change in sensitivity after 7 days of cyclic displacement. Additionally, microcantilever experiments demonstrated the high fidelity …

An Immunocompromised Patient With Cicatricial Alopecia, Dominique Revan, Victoria Stoj, Sherry Yang

Department of Dermatology and Cutaneous Biology Faculty Papers

Case description: A 37-year-old female with hemophagocytic lymphohistiocytosis presented with sudden onset hair loss that evolved over several hours during admission for neutropenic fever. Examination revealed a well-defined, tender, violaceous alopecic patch with intact follicular ostia (Fig 1). A punch biopsy showed ulcer with nonspecific changes. All fungal, bacterial, and mycobacterial stains were negative. During hospitalization, she was diagnosed with methicillin-resistant staphylococcus aureus (MRSA) bacteremia and discharged on intravenous daptomycin. She presented to the dermatology clinic 1 week later with worsening pain and hair loss, now with loss of follicular ostia.

Porokeratosis Ptychotropica Mimicking A Herpes Simplex Virus Infection, Erin R. Pomerantz, Jayci G. Rhein, Jason B. Lee, Sylvia Hsu

Department of Dermatology and Cutaneous Biology Faculty Papers

Introduction

Porokeratosis encompasses a group of skin disorders characterized by abnormal keratinization, with the defining histologic feature of cornoid lamellae, which are stacks of parakeratotic cells that overlie dyskeratotic keratinocytes. Several subtypes of porokeratosis have been identified, including disseminated superficial actinic porokeratosis, porokeratosis of Mibelli, linear porokeratosis, porokeratosis palmaris et plantaris disseminata, punctate porokeratosis, and porokeratosis ptychotropica (PP).¹ Although risk factors for other forms of porokeratosis, such as UV exposure, immunosuppression, and genetic predisposition, have been identified, PP remains less understood. Clinically, PP typically presents as hyperkeratotic, verrucous plaques found bilaterally in the gluteal cleft and buttocks.^{2, …}

Foam Fortification: Effect Of Perfluorocarbon Gases On The Stability Of Sclerosing Agent Foams, Henry Ruhl, Felipe M. Berg, Amir A. Rahnemai-Azar, Salim Abboud, Agata A. Exner

Faculty Scholarship

Purpose: To evaluate the impact of incorporating perfluorocarbons (PFCs), specifically octafluoropropane (C₃F₈) and perfluorobutane (C₄F₁₀), on the stability of sodium tetradecyl sulfate (STS)–based foams. Materials and Methods: Tessari method was employed to generate foams. C₃F₈ and C₄F₁₀ were compared with room air due to their known characteristic as gas vesicle stabilizers. Each trial set encompassed ratios of 4, 3, 2, 1.5:1 mL of gas-to-STS. Foam decay (1 − percent foam remaining in syringe) was monitored using a 4K camera over 1 hour, followed by hourly snapshots for 3 hours. All trials were repeated in triplicate. Statistical analysis was carried out …

Systems Framework For Post-Hospital Follow-Up Care Of Small And/Or Sick Newborns: A Pathway To Sustainable And Scalable Quality Care In Low-Resource, High-Burden Countries, Samudragupta Bora

Faculty Scholarship

South Asian and Sub-Saharan African countries, disproportionately overrepresented in the World Bank's low- and middle-income categories, bear a high burden of small and/or sick newborns. It is important to acknowledge that, in addition to reducing mortality, creating opportunities to enhance their health and well-being, thereby improving quality of life, is an essential metric for evaluating neonatal care success. With increased survival rates for small and/or sick newborns in most high-burden, resource-constrained settings, developing and strengthening specialized, structured neonatal follow-up programs to provide high-quality post-hospital care is imperative for optimizing outcomes and quality of life. This paper proposes a Systems Framework …

Impact Of Sociodemographic, Clinical, And Intervention Characteristics On Pain Intensity Within A Single Music Therapy Session, Samuel N. Rodgers-Melnick, Douglas Gunzler, Thomas E. Love, Siran M. Koroukian, Mark Beno, Jeffery A. Dusek, Johnie Rose

Faculty Scholarship

Several studies support the efficacy of music therapy (MT) for reducing pain, but few have examined which interventions are most effective or which patients are more likely to respond. This study investigated which sociodemographic, clinical, and intervention characteristics are associated with clinically significant reductions in pain intensity (0–10 numeric rating scale reduction ≥2 units) within a single MT session. We conducted a retrospective review of 2039 MT sessions provided across a large health system among 1203 adult patients reporting pre-session pain ≥4/10, a complete post-session pain score, and a complete pre-session stress score. We employed a multivariable logistic mixed effects …

Integrating Environmental Impact Assessment Into International Shipping Governance : A Bbnj-Pssa Synergy Framework, Thi Thuy Linh Pham

World Maritime University Dissertations

No abstract provided.

Apol2 Stabilizes Ku80 To Confer Nhej-Mediated Radioresistance In Gastric Cancer, Dan Zu, Qimei Bao, Hanyi He, Yuke Zhong, Mingcong Deng, Yangchan Hu, Chunkai Zhang, Chen Liang, Yixing Huang, Haidong Liu, Xiao Li, Yanhua He, Guoyan Luo, Weixin Wu, Fenghui Guan, Shengfeng Xu, Min Liu, Albino Bacolla, Ji Jing, Yian Du, John A Tainer, Yin Shi, Zu Ye, Xiangdong Cheng

Faculty, Staff and Student Publications

Radiotherapy is one of the most important adjuvant treatment methods for gastric cancer (GC). However, radioresistance remains a major clinical obstacle. In this study, APOL2 is identified as a key player in promoting non-homologous end joining (NHEJ)-mediated double-strand break (DSB) repair and enhancing radioresistance in GC. Bioinformatics and clinical data revealed that high APOL2 expression is correlated with poor prognosis in GC patients. Functional experiments showed that APOL2 overexpression enhances genomic stability by accelerating DSB repair via the NHEJ pathway, while APOL2 knockout impairs repair capacity. Mechanistically, APOL2 binds to and stabilizes Ku80 by enhancing USP7-mediated deubiquitylation, thereby increasing Ku80 …

Point/Counterpoint: Upfront Braf Inhibition For Adult Braf-Mutant High-Grade Gliomas, Sebastien Perreault, Marjolein Geurts, Jasia Mahdi, Karisa C Schreck, Matthias Preusser, Patrick Y Wen, Mary Jane Lim-Fat, Jan-Michael Werner

Faculty, Staff and Students Publications

No abstract provided.

Sensory-Selective Peripheral And Neuraxial Nerve Blockade With 2',6'-Pipecoloxylidide, Claire A Ostertag-Hill, Shuanglong Chen, Tianrui Xue, Rachelle Shao, Matthew Torre, Bin Feng, Zahra Vahedi, Longtu Chen, Steven J Staffa, Yueqin Zheng, Daniel S Kohane

Duncan NRI Faculty and Staff Publications

Background: Safe sensory-selective local anesthetics would be a major advance in the management of acute and chronic pain. This articles describes the sensory-selective local anesthetic properties and the toxicity profile of a known metabolite of amino-amide local anesthetics, 2',6'-pipecoloxylidide (PPX).

Methods: PPX was synthesized and made into its hydrochloride salt. PPX or ropivacaine (ROP) were injected at the sciatic nerve or intrathecally in rats, who then underwent modified hotplate (sensory) testing and weight-bearing (motor) testing. Rats injected with PPX or ROP were assessed for clinical toxicity endpoints. Conduction blockade was studied with single-unit recordings in mice. Biocompatibility was assessed histologically. …

A Rare Molecular Diagnosis In A Patient With Hepatocerebral Syndrome Contributes To The Expansion Of The Phenotypic Spectrum Of Polg2 -Related Mitochondrial Disorder, Vittoria Rossi, Dan Brooks, Hongzheng Dai, Elizabeth Mizerik, Karla Salazar, Daniel Davila-Williams, Yishay Ben-Moshe, Seema R Lalani, Sarah H Elsea, Charul Gijavanekar, Daryl A Scott, Keren Machol, Mir Reza Bekheirnia, Fernando Scaglia

Faculty, Staff and Students Publications

POLG2 encodes an accessory subunit in DNA polymerase gamma that is required for mitochondrial DNA synthesis. Monoallelic pathogenic variants in POLG2 are associated primarily with progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant type 4 (PEOA4, MIM #610131). We report a rare case of severe infantile hepatocerebral syndrome associated with biallelic variants in POLG2. The proband, a 5-week-old female infant, presented with seizures and acute liver failure. Extensive metabolic workup, including untargeted metabolomics analysis and elevated plasma growth differentiation factor 15, was suggestive of mitochondrial dysfunction. Rapid trio genome sequencing identified compound heterozygous variants, a likely pathogenic variant and …

Can Interpersonal Trust Predict And Account For Symptom Change During Group Cognitive Processing Therapy For Ptsd? An Investigation Of The Iterated Trust Game, M Wright Williams, Christopher Hunt, David P Graham, Matt Estey, Lia Smith, Katherine Mccurry, Brooks King-Casas, Pearl Chiu

Faculty, Staff and Students Publications

Objective: Group cognitive processing therapy (GCPT) is frequently utilized to treat PTSD within the VA healthcare system, but its mechanisms are not well understood. Interpersonal trust could be an important change process in GCPT given its relevance to group-based therapy and its role in CPT, but self-report measures are inadequate for capturing the dynamic interplay that defines interpersonal trust. Here, we examined the degree to which interpersonal could predict and account for PTSD symptom change in GCPT using the iterated trust game (ITG)-a behavioral task used to approximate real-world trust behavior.

Methods: Participants were Veterans with PTSD who participated in …

Pathogenic Xpo1 Variants Cause A Dominant Neurodevelopmental Disorder, Amber S E Van Oirsouw, Pavla Nedbalova, Miroslava Hancarova, Jan Prchal, Darina Prchalova, Marketa Vlckova, Sarka Bendova, Kristin G Monaghan, Lisa M Dyer, Yanmin Chen, Deanna Alexis Carere, Emma A M Te Bogt, Heather Fisher, Angela E Scheuerle, Stephanie Riley, Mahim Jain, Weiyi Mu, Joann N Bodurtha, Albertien M Van Eerde, Marijn F Stokman, Nicola Longo, Meena Balasubramanian, Michael Spiller, Gregory Costain, Charlotte Von Der Lippe, Kristian Tveten, Marianne Jortveit, Øystein L Holla, Bertrand Isidor, Benjamin Cogné, Kevin E Glinton, Blake Vuocolo, Roberta Ann Sierra, Brad Angle, Kelly Bontempo, Klaas Koop, Rachel Rabin, John Pappas, David A Staffenberg, Pascal Joset, Peter Miny, Isabel Filges, Abdulrazak Alali, Kara Vitalone, Jill A Rosenfeld, Weimin Bi, Samuel Bradbrook, Renee Perrier, Subhadra Ramanathan, June-Anne Gold, María Palomares Bralo, María Ángeles Gómez-Cano, Ann Haskins Olney, Shelly Nielsen, Alban Ziegler, Dominique Bonneau, Clément Prouteau, Ange-Line Bruel, Charlotte Caille-Benigni, Laëtitia Lambert, Andrea C Yu, Nathaniel H Robin, Dana Goodloe, Jan Fischer, Joseph Porrmann, Yvonne D Hennig, Rami Abou Jamra, Isabella Herman, Ivy R Johnson, Lucas Hérissant, Guillaume Jouret, Koen L I Van Gassen, Ellen Van Binsbergen, Bert Van Der Zwaag, Alwin Kamermans, Renske Oegema, Zdenek Sedlacek, Michaela Fenckova, Richard H Van Jaarsveld

Faculty, Staff and Students Publications

Purpose: XPO1 functions in key cellular processes, including nucleo-cytoplasmic export and mitosis. The gene is deleted in a subset of patients with the 2p15p16.1 microdeletion syndrome; however, no monogenic XPO1-related disorder has been described to date.

Methods: We collected clinical data of individuals with de novo XPO1 variants through online matchmaking. We used Drosophila to study XPO1 function in development and habituation learning.

Results: A total of 22 individuals met the criteria to be included in the main study cohort. Of these, half have putative loss-of-function variants, and half have coding variants (10 missense and 1 in-frame deletion variant). We …

Glycerol-3-Phosphate Activates Chrebp, Fgf21 Transcription And Lipogenesis In Citrin Deficiency, Vinod Tiwari, Byungchang Jin, Olivia Sun, Edwin D J Lopez Gonzalez, Min-Hsuan Chen, Xiwei Wu, Hardik Shah, Andrew Zhang, Mark A Herman, Cassandra N Spracklen, Russell P Goodman, Charles Brenner

Faculty, Staff and Students Publications

Citrin deficiency (CD) is caused by the inactivation of SLC25A13, a mitochondrial membrane protein required to move electrons from cytosolic NADH to the mitochondrial matrix in hepatocytes. People with CD do not like sweets. Here we show that SLC25A13 loss causes the accumulation of glycerol-3-phosphate (G3P), which activates the carbohydrate response element-binding protein (ChREBP) to transcribe FGF21, which acts in the brain to restrain intake of sweets and alcohol and to transcribe key genes driving lipogenesis. Mouse and human data suggest that G3P-ChREBP is a mechanistic component of the Randle Cycle that contributes to metabolic-dysfunction-associated steatotic liver disease and forms …

Information Theory Analysis Of Ctx Shows Consistent Clinical Presentation, Jennifer Hanson, Penelope E Bonnen

Faculty, Staff and Students Publications

Cerebrotendinous xanthomatosis (CTX) is a rare, metabolic disorder caused by pathogenic variants in CYP27A1. The classic clinical presentation includes infantile-onset chronic diarrhea, juvenile-onset bilateral cataracts, with development of tendon xanthomas and progressive neurological dysfunction. These multisystem clinical features typically appear in different decades of life often confounding diagnosis of CTX. Further complicating diagnosis is the generally held belief that the clinical presentation of CTX varies highly between individuals and even within families. We applied information theory analyses to CTX patient data to quantitatively assess clinical variability in CTX. We conducted a systematic review of the literature to identify all CTX …

Mutations In The Key Autophagy Tethering Factor Epg5 Link Neurodevelopmental And Neurodegenerative Disorders Including Early-Onset Parkinsonism, Hormos Salimi Dafsari, Celine Deneubourg, Kritarth Singh, Reza Maroofian, Zita Suprenant, Ay Lin Kho, Neil J Ingham, Karen P Steel, Preethi Sheshadri, Franciska Baur, Lea Hentrich, Birgit Gerisch, Mina Zamani, Cesar Alves, Ata Siddiqui, Haidar S Dafsari, Mehri Salari, Anthony E Lang, Michael Harris, Alice Abdelaleem, Saeid Sadeghian, Reza Azizimalamiri, Hamid Galehdari, Gholamreza Shariati, Alireza Sedaghat, Jawaher Zeighami, Daniel Calame, Dana Marafi, Ruizhi Duan, Adrian Boehnke, Gary D Clark, Jill A Rosenfeld, Carrie A Mohila, Dora Steel, Saurabh Chopra, Suvasini Sharma, Nicolai Kohlschmidt, Steffi Patzer, Afshin Saffari, Darius Ebrahimi-Fakhari, Büşra Eser Çavdartepe, Irene J Chang, Erika Beckman, Renate Peters, Andrew Paul Fennell, Bernice Lo, Luisa Averdunk, Felix Distelmaier, Martina Baethmann, Frances Elmslie, Kairit Joost, Sheela Nampoothiri, Dhanya Yesodharan, Hanna Mandel, Amy Kimball, Antonie D Kline, Cyril Mignot, Boris Keren, Vincent Laugel, Katrin Õunap, Kalpana Devadathan, Frederique M C Van Berkestijn, Arpana Silwal, Saskia Koene, Sumit Verma, Mohammed Yousuf Karim, Chahynez Boubidi, Majid Aziz, Gehad Elghazali, Lauren Mattas, Mohammad Miryounesi, Farzad Hashemi-Gorji, Shahryar Alavi, Nayereh Nouri, Mehrdad Noruzinia, Saeideh Kavousi, Arveen Kamath, Sandeep Jayawant, Russell Saneto, Nourelhoda A Haridy, Pinar Ozkan Kart, Ali Cansu, Madeleine Joubert, Claire Beneteau, Kyra E Stuurman, Martina Wilke, Tahsin Stefan Barakat, Homa Tajsharghi, Annarita Scardamaglia, Sadeq Vallian, Semra Hız, Ali Shoeibi, Reza Boostani, Narges Hashemi, Meisam Babaei, Norah Saleh Alsaleh, Julie Porter, Tania Attié-Bitach, Pauline Marzin, Dorota Wicher, Jessica I Gold, Elisabeth Schuler, Amna Kashgari, Rakan F Alanazi, Wafaa Eyaid, Marc Engelen, Mirjam Langeveld, Burkhard Stüve, Yun Li, Gökhan Yigit, Bernd Wollnik, Mariana H G Monje, Dimitri Krainc, Niccolò E Mencacci, Somayeh Bakhtiari, Michael Kruer, Emanuela Argilli, Elliott Sherr, Yalda Jamshidi, Ehsan Ghayoor Karimiani, Yiu Wing Sunny Cheung, Ivan Karin, Giovanni Zifarelli, Peter Bauer, Wendy K Chung, James R Lupski, Manju A Kurian, Jörg Dötsch, Jürgen-Christoph Von Kleist-Retzow, Thomas Klopstock, Matias Wagner, Calvin Yip, Andreas Roos, Rita Carsetti, Carlo Dionisi-Vici, Mathias Gautel, Michael R Duchen, Adam Antebi, Henry Houlden, Manolis Fanto, Heinz Jungbluth

Faculty, Staff and Students Publications

Objective: Autophagy is a fundamental biological pathway with vital roles in intracellular homeostasis. During autophagy, defective cargoes including mitochondria are targeted to lysosomes for clearance and recycling. Recessive truncating variants in the autophagy gene EPG5 have been associated with Vici syndrome, a severe early-onset neurodevelopmental disorder with extensive multisystem involvement. Here, we aimed to delineate the extended, age-dependent EPG5-related disease spectrum.

Methods: We investigated clinical, radiological, and molecular features from the largest cohort of EPG5-related patients identified to date, complemented by experimental investigation of cellular and animal models of EPG5 defects.

Results: Through worldwide collaboration, we identified 211 patients, 97 …