Digital Commons Network^™

Investigating The Role Of Metallothioneins In Fungal Iron Homeostasis, David Eap

Theses and Dissertations

The pathogenic fungi Aspergillus fumigatus requires metals to survive and infect humans, but metal overload can be detrimental. Metallothioneins (MTs) are small, cysteine-rich proteins that alleviate metal toxicity by binding excess metals (typically Zn or Cu) for storage or delivery. A recent report indicates that the Fe-S cluster binding glutaredoxin GrxD and the putative Cu-MT CmtA were interacting under high iron conditions in A. fumigatus. We hypothesize that this MT may have a role in binding iron or Fe-S clusters under iron overload conditions to prevent iron toxicity. We also aim to characterize this new MT by determining its …

Circannual And Kinship Cues Shape Reproduction And Epigenetic Aging In Peromyscus, Kim Tuyen Huynh Dam

Theses and Dissertations

Evolutionary success is defined by the ability of a species to adapt and survive across many generations. This success is not determined by any single attribute but rather includes the entrenched, complex system that could be associated with biological rhythms, reproductive strategies, and regulations of epigenetic and genetic components. By using closed Peromyscus colonies as a model and by coupling mathematical modeling, analyses of breeding records, epigenetic studies, and in vitro and in vivo experiments, this dissertation aims to discover how Peromyscus adjusts to the internal and external pressures to ensure their survival and preserve evolutionary fitness in controlled environments. …

Exploring The Ancestry And Mutational Signatures Of Free-Breeding Dogs From Chernobyl And The Galápagos Islands, Gabriella Jean Spatola

Theses and Dissertations

Two free-breeding dog populations, one in Chernobyl, Ukraine, and the other on the Galápagos Islands, Ecuador, exist on opposite sides of the globe, yet both hold unique scientific potential to further our understanding of free-breeding dog population dynamics and evolutionary processes related to their environments. In the following studies, blood samples from more than 400 individual Chernobyl dogs were collected and their genomes were analyzed alongside over 1500 purebred and 200 global free-breeding dogs, describing genetic relationships and the extent of admixture with purebred migrants. Importantly, the sampled Chernobyl dogs had long-term exposures to ionizing radiation because of the 1986 …

Hybrid Penstemon Flowers: Colors, Pigments, And Detectability & Experimental Teaching: Evaluating The Impact Of Active Learning, Josh Thomas Edward Stevens

Theses and Dissertations

Shifts to different primary pollinators are often accompanied by changes in suites of floral traits. Understanding how and why these floral adaptations evolve is a central goal in evolutionary biology. Within the genus Penstemon, the transition from bee-pollinated to hummingbird-pollinated flowers is a common evolutionary pattern. These pollinator shifts have caused several closely related species to exhibit distinct pollination syndromes. One example of this evolutionary phenomenon can be seen within the sister species P. eatonii (hummingbird-pollinated) and P. laevis (bee-pollinated). These two species form several hybrid zones, in which hybrid individuals exhibit colors resembling both parental species, along with a …

Investigating Mechanisms And Day-Level Factors That Influence Children’S 24-Hour Movement Behaviors, Hannah Parker

Theses and Dissertations

Twenty-four hour movement behaviors (i.e., physical activity (PA), screen time (ST), and sleep) are associated with health outcomes, chronic disease (obesity, type 2 diabetes), and mortality. Most literature evaluating children’s 24-hour movement behaviors has focused on static person-level demographic information such as age or biological sex. Relatively less work has examined the variable factors that change day to day, such as environment or context. The Structured Days Hypothesis (SDH) suggests that when children are in structured environments, they have healthier movement behaviors compared to less structured environments where children have more discretionary time to engage in obesogenic behaviors. Besides school/childcare, …

Conservation Management Effects On Soil And Agronomic Properties In A Furrow-Irrigated Corn System In East-Central Arkansas, Jeferson P. Pimentel, Christopher G. Henry, Kris R. Brye, Benjamin R. Runkle, Amanda J. Ashworth, Edgar Mersiovsky, Kevin C. Thompson

Biological and Agricultural Engineering Faculty Publications and Presentations

Cover crops can improve soil physical properties and help to sustain agricultural crop yields. A 6-year study conducted from 2017 to 2022 examined the effects of conservation soil management practices in a furrow-irrigated continuous corn (Zea mays L.) system on a silt-loam soil (Typic Albaqualf) in the Lower Mississippi River Delta region of eastern Arkansas. This study compared the effects of conventional tillage (CT), no-tillage (NT), and no-tillage with cover crops (CC) in selected soil physical and chemical properties (i.e., soil bulk density (D b), porosity (& fnof;t), field capacity (Theta FC), Permanent wilting point (Theta PWP), Plant available water …

Blue Light Is A Key Factor In Regulating Stomatal Movement, Transpiration Rate And Aba Metabolism Under Varying Vapour Pressure, Sheona Noemi Innes, Sara Brunborg Jakobsen, Rikke Bryn Røsåsen, Haider Ali, Knut Asbjørn Solhaug, Jorunn Elisabeth Olsen, Sissel Torre

Research outputs 2022 to 2026

Vapour pressure deficit (VPD) and blue light (BL) are import signals for stomatal regulation and highly relevant during cultivation of economically important crops such as cucumber in controlled environments. However, the information about combined effects of VPD and BL and the regulation of abscisic acid (ABA) in this respect, is limited and seems to vary between species. This study investigated how moderate (1.12 kPa) or low (0.28 kPa) VPD combined with 5% or 30% BL affect the foliar ABA metabolism, transpiration rate, nutrient uptake, and growth in well-watered cucumber plants (Cucumis sativus ‘Quatro’). Additional BL, regardless of VPD, resulted in …

Cross-Continental Analysis Shows That Disturbance Effects On Reptile Body Condition Do Not Predict Abundance Responses, Kristina J. Macdonald, Don A. Driscoll, Michael D. Craig, Robert A. Davis, Steven J. Hromada, C. M. Gienger, Lee A. Fitzgerald, Daniel J. Leavitt, Danielle K. Walkup, Rickard Abom, Adrian F. Wayne, Gordon R. Friend, Brent Johnson, Danielle Stokeld, Chris R. Dickman, Scott A. Thompson, Graham G. Thompson, Daniel F. Bohórquez Fandiño, Christopher K. Woolley, Annabel L. Smith, Calum Irvine, Tim S. Jessop, Jade E. Keehn, Chris R. Feldman, Xavier Santos, Josabel Belliure

Research outputs 2022 to 2026

Ecological disturbances are discrete events that alter or transform the physical, chemical, or biological characteristics of ecosystems. Disturbance can cause animal populations to decline and, according to the risk-disturbance hypothesis and population collapse framework, these declines can be predicted by declines in animal body condition. However, no research has empirically examined the general relationship between body condition and abundance, nor their relationship in response to disturbance. We used a combined dataset representing 33 studies and > 42,000 observations of 75 species from Australia, New Zealand, Spain and the United States of America to test predictions relating to the relationship between reptile …

Dynamic Microbiome Responses To Structurally Diverse Anthocyanin-Rich Foods In A Western Diet Context, Mohammed F. Almatani, Giovanni Rompato, Eliza C. Stewart, Marcus Hayden, Jeremy Case, Samuel Rice, Korry J. Hintze, Abby D. Benninghoff

Animal, Dairy, and Veterinary Science Student Research

Background/Objectives: Anthocyanin (ACN)-rich foods are known to influence the gut microbiota composition, but the temporal dynamics and structural specificity of these effects remain poorly understood. This study investigated how distinct ACN-rich fruit supplements impact the gut microbiome over time in the context of a Western-style diet. We hypothesized that ACN-induced microbial shifts would occur rapidly, differ by ACN source, and require continued intake to persist. Methods: C57BL/6J mice were fed the total Western diet (TWD) supplemented with freeze-dried powders from bilberry (BB), tart cherry (TC), chokeberry (CB), elderberry (EB), black currant (BC), or black raspberry (BRB) for 0, 1, 3, …

Basic Rabbit Selection And Breeding Considerations, Joseph Okoh, Jessie Hadfield

All Current Publications

This fact sheet is designed to assist rabbit producers in understanding breed selection for a profitable enterprise. It can also serve as a training tool for new producers, aiding them in breed selection and breeding practices.

Protocol To Detect M22g Modification On Single Trna Iso-Decoders By Immuno-Northern Blotting, Sseu-Pei Hwang, Katherine Barondeau, Catherine Denicourt

Faculty, Staff and Student Publications

tRNA modifications are highly dynamic and play crucial roles in regulating gene expression. Here, we present an assay for analyzing N2, N2-dimethylguanosine (m22G) modifications on tRNAs using an antibody-based detection approach. We describe steps for isolating tRNAs from human cells via ion-exchange chromatography, capturing specific tRNA iso-decoders on streptavidin magnetic beads, and detecting modifications through immuno-northern blotting. This approach enables researchers to investigate other tRNA modifications using specific antibodies or downstream approaches such as mass spectrometry.

Coordinated Regulation By Lncrnas Results In Tight Lncrna-Target Couplings, Hua-Sheng Chiu, Sonal Somvanshi, Chung-Te Chang, Eric James De Bony De Lavergne, Zhaowen Wei, Chih-Hung Hsieh, Wim Trypsteen, Kathleen A Scorsone, Ektaben Patel, Tien T Tang, David B Flint, Mohammad Javad Najaf Panah, Hyunjae Ryan Kim, Purva Rathi, Yan-Hwa Wu Lee, Sarah E Woodfield, Sanjeev A Vasudevan, Andras Attila Heczey, M Waleed Gaber, Gabriel O Sawakuchi, Ting-Wen Chen, Pieter Mestdagh, Xuerui Yang, Pavel Sumazin

Faculty, Staff and Student Publications

The determination of long non-coding RNA (lncRNA) function is a major challenge in RNA biology with applications to basic, translational, and medical research. We developed BigHorn to computationally infer lncRNA-DNA interactions that mediate transcription and chromatin-remodeling factor activity. Its accurate inference enabled the identification of lncRNAs that coordinately regulate both the transcriptional and post-transcriptional processing of their targets. These lncRNAs may act as molecular chaperones, regulating the stability and translation of mRNAs they helped transcribe, leading to tightly coupled expression profiles. Our analysis suggests that lncRNAs regulate cancer genes across tumor contexts, thus propagating the effects of non-coding alterations to …

Crem Is A Regulatory Checkpoint Of Car And Il-15 Signalling In Nk Cells, Hind Rafei, Rafet Basar, Sunil Acharya, Yu-Sung Hsu, Pinghua Liu, Deqiang Zhang, Toszka Bohn, Qingnan Liang, Vakul Mohanty, Ranjan Upadhyay, Ping Li, Pravin Phadatare, Merve Dede, Donghai Xiong, Huihui Fan, Corry Mathew Jones, Sebastian Kunz, May Daher, Ana Karen Nunez Cortes, Mayra Shanley, Bin Liu, Sadie Mae Moseley, Chenyu Zhang, Dexing Fang, Pinaki Banerjee, Nadima Uprety, Ye Li, Rejeena Shrestha, Xinhai Wan, Hong Shen, Vernikka Woods, April Lamour Gilbert, Seema Rawal, Jinzhuang Dou, Yukun Tan, Jeong-Min Park, Francia Reyes Silva, Alexander Biederstädt, Mecit Kaplan, Xin Ru Jiang, Inci Biederstädt, Bijender Kumar, Silvia Tiberti, Madison Moore, Jingling Jin, Ryan Z Yang, Luis Muniz-Feliciano, Samuel Rosemore, Paul Lin, Gary M Deyter, Natalie Wall Fowlkes, Abhinav K Jain, David Marin, Anirban Maitra, Ken Chen, Tobias Bopp, Elizabeth J Shpall, Katayoun Rezvani

Faculty, Staff and Student Publications

Chimeric antigen receptor (CAR) natural killer (NK) cell immunotherapy offers a promising approach against cancer1-3. However, the molecular mechanisms that regulate CAR-NK cell activity remain unclear. Here we identify the transcription factor cyclic AMP response element modulator (CREM) as a crucial regulator of NK cell function. Transcriptomic analysis revealed a significant induction of CREM in CAR-NK cells during the peak of effector function after adoptive transfer in a tumour mouse model, and this peak coincided with signatures of both activation and dysfunction. We demonstrate that both CAR activation and interleukin-15 signalling rapidly induce CREM upregulation in NK cells. Functionally, CREM …

A Lysosomal Surveillance Response To Stress Extends Healthspan, Terytty Yang Li, Arwen W Gao, Rendan Yang, Yu Sun, Yuxuan Lei, Xiaoxu Li, Lin Chen, Yasmine J Liu, Rachel N Arey, Kimberly Morales, Raya B Liu, Wenzheng Wang, Ang Zhou, Tong-Jin Zhao, Weisha Li, Amélia Lalou, Qi Wang, Tanes Lima, Riekelt H Houtkooper, Johan Auwerx

Faculty, Staff and Students Publications

Lysosomes are cytoplasmic organelles central for the degradation of macromolecules to maintain cellular homoeostasis and health. However, how lysosomal activity can be boosted to counteract ageing and ageing-related diseases remains elusive. Here we reveal that silencing specific vacuolar H+-ATPase subunits (for example, vha-6), which are essential for intestinal lumen acidification in Caenorhabditis elegans, extends lifespan by ~60%. This longevity phenotype can be explained by an adaptive transcriptional response typified by induction of a set of transcripts involved in lysosomal function and proteolysis, which we termed the lysosomal surveillance response (LySR). LySR activation is characterized by boosted lysosomal activity …

Histone Lysine Methyltransferases Mll3 And Mll4 Direct Gene Expression To Produce Platelets Efficiently, Guozhen Gao, Josimar Dornelas Moreira, Prosun Das, Kevin Lin, Kai Ge, Taiping Chen, Yue Lu, Margarida A Santos

Faculty, Staff and Student Publications

Circulating blood platelets are responsible for maintaining hemostasis. They are released into blood vessels from mature megakaryocytes. Although several transcription factors have been reported to orchestrate the transcriptional programs required for platelet production, how chromatin regulators control these processes is still poorly understood. MLL3 and MLL4 are the main lysine methyltransferases responsible for the deposition of H3K4me1 histone marks at enhancers. MLL3 and MLL4 typically form complexes with other co-factors, such as PTIP. Recently, we showed that loss of PTIP leads to decreased platelet numbers in mice. Here, we find that, although MLL3/4 double deficiency does not alter megakaryopoiesis and …

Autologous T Cell Therapy For Prame, Martin Wermke, Dejka M Araujo, Manik Chatterjee, Apostolia M Tsimberidou, Tobias A W Holderried, Amir A Jazaeri, Ran Reshef, Carsten Bokemeyer, Winfried Alsdorf, Katrin Wetzko, Peter Brossart, Katrin Aslan, Linus Backert, Sebastian Bunk, Jens Fritsche, Swapna Gulde, Silvana Hengler, Norbert Hilf, Mohammad B Hossain, Jens Hukelmann, Mamta Kalra, Delfi Krishna, M Alper Kursunel, Dominik Maurer, Andrea Mayer-Mokler, Regina Mendrzyk, Ali Mohamed, Karine Pozo, Arun Satelli, Marilena Letizia, Heiko Schuster, Oliver Schoor, Claudia Wagner, Hans-Georg Rammensee, Carsten Reinhardt, Harpreet Singh-Jasuja, Steffen Walter, Toni Weinschenk, Jason J Luke, Cedrik M Britten

Faculty, Staff and Student Publications

In contrast to chimeric antigen receptor T cells, T cell receptor (TCR)-engineered T cells can target intracellular tumor-associated antigens crucial for treating solid tumors. However, most trials published so far show limited clinical activity. Here we report interim data from a first-in-human, multicenter, open-label, 3 + 3 dose-escalation/de-escalation phase 1 trial studying IMA203, an autologous preferentially expressed antigen in melanoma (PRAME)-directed TCR T cell therapy in HLA-A*02+ patients with PRAME+ recurrent and/or refractory solid tumors, including melanoma and sarcoma. Primary objectives include the evaluation of safety and tolerability and the determination of the maximum tolerated dose (MTD) and/or recommended dose …

Memantine Inhibits Calcium-Permeable Ampa Receptors, Elisa Carrillo, Alejandra Montaño Romero, Cuauhtemoc U Gonzalez, Andreea L Turcu, Santiago Vázquez, Edward C Twomey, Vasanthi Jayaraman

Faculty, Staff and Student Publications

Memantine is an US Food and Drug Administration (FDA) approved drug that is thought to selectively inhibit NMDA-subtype of ionotropic glutamate receptors (NMDARs). NMDARs enable calcium influx into neurons and are critical for normal brain function. However, increasing evidence shows that calcium influx in neurological diseases is augmented by calcium-permeable AMPA-subtype ionotropic glutamate receptors (AMPARs). Here, we demonstrate that these calcium-permeable AMPARs (CP-AMPARs) are inhibited by memantine. Electrophysiology unveils that memantine inhibition of CP-AMPARs is dependent on their calcium permeability and the presence of their neuronal auxiliary subunit transmembrane AMPAR regulatory proteins (TARPs). Through cryo-electron microscopy we elucidate that memantine …

Using Radium Isotopes To Compare Nutrient Inputs Via Submarine Groundwater Discharge To Offshore Export On The West Florida Shelf, Andrew L. Lindgren

OES Theses and Dissertations

Radium isotopes have been used to trace submarine groundwater discharge (SGD) and associated nutrient and metal inputs into the coastal ocean. They have also been used to estimate rates of diffusive mixing and export fluxes of dissolved constituents offshore. However, use of both approaches in tandem to determine the fate of groundwater inputs after they enter the coastal ocean is still relatively unexplored. Radium isotopes and nutrients were measured in two cross-shelf cruises on the West Florida Shelf in different seasons and in quarterly sampling of offshore wells. Through 226Ra mass balance and 223Ra-derived diffusive mixing rates, inputs of nutrients …

Functional Regulation Of Macrophages By Ces1d-Mediated Lipid Signaling In Immunometabolism, Long J Shao, Fathima Elizondo, Feng Gao, Rabie Habib, Xin Li, Katherine Pham, Jazmin Ysaguirre, Maryam Elizondo, Shirindokht Shirazi, Kristin L Eckel-Mahan, Sean Hartig, Huaizhu Wu, Kai Sun

Faculty, Staff and Student Publications

Objective: Macrophage accumulation in metabolically active tissues during obesity is common in both animals and humans, but the lipid signaling mechanisms that trigger macrophage inflammation remain unclear. This study investigates the role of Ces1d, an unconventional lipase, in regulating macrophage inflammation under nutritional stress.

Methods: A myeloid-specific Ces1d knockout (LysM-Cre-Ces1d floxed/floxed, KO) mouse model was used for the studies. For in vitro tests, bone marrow-derived macrophages (BMDMs) from control (Ces1d floxed/floxed, WT) and KO mice were assessed for migration, polarization, and activation. For in vivo experiments, WT and KO mice were induced to obesity via a high-fat diet (HFD) and …

The Landscape Of Malignant Transition: Unraveling Cancer Cell-Of-Origin And Heterogeneous Tissue Microenvironment, Ruihan Luo, Jiajia Liu, Tiangang Wang, Weiling Zhao, Yanfei Wang, Jianguo Wen, Hongyu Wang, Shanli Ding, Xiaobo Zhou

Faculty, Staff and Student Publications

Understanding disease progression and sophisticated tumor ecosystems is imperative for investigating tumorigenesis mechanisms and developing novel prevention strategies. Here, we dissected heterogeneous microenvironments during malignant transitions by leveraging data from 1396 samples spanning 13 major tissues. Within transitional stem-like subpopulations highly enriched in precancers and cancers, we identified 30 recurring cellular states strongly linked to malignancy, including hypoxia and epithelial senescence, revealing a high degree of plasticity in epithelial stem cells. By characterizing dynamics in stem-cell crosstalk with the microenvironment along the pseudotime axis, we found differential roles of ANXA1 at different stages of tumor development. In precancerous stages, reduced …

Outcomes And Toxicity Following 3 Or More Definitive Courses Of Thoracic Radiation Therapy For Non-Small Cell Lung Cancer, Abigael Odwuor, Percy Lee, Joe Y Chang, Saumil Gandhi, Zhongxing Liao, Steven H Lin, Aileen Chen, Quynh-Nhu Nguyen, Michael S O'Reilly, Stephen G Chun, Julianna Bronk, David Qian, Matthew S Ning

Faculty, Staff and Student Publications

Purpose: Salvage re-irradiation is increasingly utilized to manage non-small cell lung cancer (NSCLC) locoregional recurrence or new lung primaries in previously treated areas. There is sparse information on efficacy and toxicity profile. We report a large experience of patients treated with multiple courses of definitive radiation for new and recurrent NSCLC.

Methods and materials: Medical records of patients who underwent ≥ 3 definitive thoracic radiation therapy (RT) courses for new or recurrent NSCLC at our cancer center from 2012 through 2021 were retrospectively reviewed following institutional review board approval. Toxicity was graded per Common Terminology Criteria for Adverse Events (CTCAE) …

Renal G Protein-Coupled Estrogen Receptor 1 Regulates The Epithelial Sodium Channel Promoting Natriuresis To A Greater Extent In Females, Victoria L Nasci, Jean C Bopassa, Elena Mironova, Megan Rhoads, Ravneet Singh, Dennis P Buehler, David M Pollock, Oleh M Pochynyuk, James D Stockand, Eman Y Gohar

Faculty, Staff and Student Publications

Hypertension prevalence is lower in women than men. Enhanced renal sodium (Na+) handling in females has been implicated in sex-differences in hypertension. Epithelial Na+ channel (ENaC) is a key contributor to Na+ homeostasis and is regulated by estrogen. Recent evidence suggests G protein-coupled estrogen receptor 1 (GPER1) evokes a female-specific natriuresis that involves endothelin-1 (ET-1). ET-1 has been shown to downregulate ENaC activity, but whether GPER1 regulates ENaC to modulate natriuresis is unknown. We tested the hypothesis that renal GPER1 functionally interacts with ENaC to promote natriuresis in a sex-specific manner. RNAscope confirmed co-expression of GPER1 and ENaC in rat …

Ovarian Cancer Risk And Survival According To Tumor Sex Hormone Receptor Expression: An Ovarian Cancer Association Consortium And Ovarian Tumor Tissue Analysis Consortium Pooled Analysis, Zhuxuan Fu, Lauren Borho, Sarah E Taylor, Linda E Kelemen, Anna Defazio, Penelope M Webb, Martin Köbel, Nicola S Meagher, Renhua Na, Antonis C Antoniou, Alison H Brand, Catherine J Kennedy, Nikilyn Nevins, Paul D P Pharoah, Yurii B Shvetsov, Stacey J Winham, Jennifer Alsop, Matthias W Beckmann, Adelyn Bolithon, Jessica Boros, David D L Bowtell, James D Brenton, Michael E Carney, Anita Chudecka-Głaz, Linda S Cook, Cezary Cybulski, Peter A Fasching, Sian Fereday, Renée T Fortner, María J García, Ellen L Goode, Marc T Goodman, Jacek Gronwald, Arndt Hartmann, Brenda Y Hernandez, Estrid Høgdall, David G Huntsman, Allan Jensen, Mercedes Jimenez-Linan, Janine M Joseph, Beth Y Karlan, Ewa Kaznowska, Susanne K Kjaer, Tomasz Kluz, Jennifer M Koziak, Jenny Lester, Teri A Longacre, Maria Lycke, Valerie Mcguire, Kirsten B Moysich, Rachel A Murphy, Sandra Orsulic, Susan J Ramus, Cristina Rodríguez-Antona, Joseph H Rothstein, Spinder Samra, Weiva Sieh, Helen Steed, Karin Sundfeldt, Aline Talhouk, Jan Uciński, Chen Wang, Nicolas Wentzensen, Alice S Whittemore, Lynne R Wilkens, Thomas Songer, Maria Mori Brooks, Lu Tang, Francesmary Modugno

Faculty, Staff and Student Publications

Objective: Many epithelial ovarian cancer (EOC) risk factors relate to sex hormones. The association between these factors and the expression of androgen receptor (AR), estrogen receptor-α (ER), and progesterone receptor (PR) in tumors is unknown.

Method: We linked epidemiologic, AR/ER/PR tumor expression, and survival data from 19 studies in the Ovarian Cancer Association Consortium (OCAC; 4762 cases, 20,888 controls) and the Ovarian Tumor Tissue Analysis (OTTA) consortium (5737 cases). We estimated odds ratios (ORs) and 95 % confidence intervals (CIs) between hormonally-linked factors and tumor AR/ER/PR expression using polytomous logistic regression. We assessed survival by AR/ER/PR tumor expression overall and …

Microbial Biosensor For Sensing And Treatment Of Intestinal Inflammation, Duolong Zhu, Jeffrey Galley, Jason Pizzini, Elena Musteata, Martin V Douglas, Walter J Chazin, Eric P Skaar, Jeffrey J Tabor, Robert A Britton

Faculty, Staff and Students Publications

Synthetic biology has enabled the development of biosensors to detect intestinal inflammation, yet few target the clinically validated biomarker of intestinal inflammation calprotectin with both diagnostic and therapeutic capabilities. Here, an optimized calprotectin biosensor is presented that leverages a zinc uptake regulator (Zur) controlled promoter coupled with a memory circuit to detect and record intestinal inflammation in vivo. The level of biosensor activation strongly correlates with calprotectin levels in the colon of two independent mouse models of colitis. Coupling of the biosensor with the production of the anti-inflammatory cytokine IL10 allowed for the resolution of chemically induced colitis, demonstrating the …

Unfolding The Mystery Of Autoimmunity: The Environmental Determinants Of Diabetes In The Young (Teddy) Study, Marian Rewers, Daniel Agardh, Suzanne Bennett Johnson, Ezio Bonifacio, Helena Elding Larsson, Patricia Gesualdo, William Hagopian, Michael J Haller, Heikki Hyöty, Randi Johnson, Richard Mcindoe, Eoin Mckinney, Jessica Melin, Åke Lernmark, Richard E Lloyd, Kristian F Lynch, Jill M Norris, Stephen S Rich, Roswith Roth, Desmond Schatz, Jorma Toppari, Eric Triplett, Kendra Vehik, Suvi M Virtanen, Anette-G Ziegler, Beena Akolkar, Jeffrey P Krischer, Teddy Study Group

Faculty, Staff and Students Publications

In 2025, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at the National Institutes of Health celebrates 75 years of leadership in diabetes research. The NIDDK serves people of the U.S. affected by or at risk for many chronic diseases, including diabetes and other endocrine, metabolic, and digestive disorders, by funding innovative research to develop better treatment and prevention and a cure for these conditions. Autoimmunity that leads to type 1 diabetes or celiac disease or thyroid autoimmunity affects 1 in 20 children and adolescents in the U.S. While treatments are available, prevention of these common autoimmune …

Inhibition Of The Gsk3Β/Nav16 Complex Suppresses Early-Stage Alzheimer’S Hyperexcitability, Timothy John Baumgartner, Manuel Silva-Pérez, Zahra Haghighijoo, Nolan Michael Dvorak, Aditya Kumar Singh, Nana Aboadwe Goode, Jully Singh, Berenice Gutierrez Grebenkova, Mate Marosi, Jessica Di Re, Leandra Koff, Wissarut Wijitrmektong, Manu Bala, Hanyue Liao, Marijn Lijffijt, Adam Thomas Szafran, Michael James Bolt, Michael A Mancini, Gregory D Cuny, Diana Shu-Lian Chow, Agenor Limon, Jeannie Chin, Fernanda Laezza

Faculty, Staff and Students Publications

Introduction: Network hyperexcitability (NH) is observed in patients with early-stage Alzheimer's disease (AD), emerging decades before cognitive decline. A key molecular determinant of NH is voltage-gated Na+ channel 1.6 (Nav1.6), which mediates action potential firing in CA1 hippocampal neurons. Ameliorating NH through inhibition of the glycogen-synthase kinase 3β (GSK3β/Nav1.6 complex may provide immediate benefits to cognition and memory and slow AD progression.

Methods: Hight-throughput virtual screening and multiple in vitro biological assays were utilized to identify compound 1063. Patch-clamp electrophysiology and electroencephalogram recordings were utilized to functionally assess 1063 in models of AD neuropathology.

Results: Building on previous studies identifying …

Decoding Metastatic Microenvironments Through Single-Cell Omics Reveals New Insights Into Niche Dynamics And Tumor Evolution, Fengshuo Liu, Xiang H-F Zhang

Faculty, Staff and Students Publications

Metastasis is the predominant cause of cancer mortality, primarily driven by complex tumor-host interactions within specialized metastatic niches. Recent advances in single-cell technologies have provided unprecedented insights into metastatic niche formation, evolution and function, including how primary tumors precondition distant organs for metastases and how disseminated tumor cells dynamically interact with host cells to modulate their environments. Integrated single-cell studies across multiple cancer types have also revealed divergent and convergent metastatic adaptation strategies. These findings collectively highlight metastasis as a dynamic, cooperative process shaped by intricate tumor-host interactions, and provide a foundation for novel therapeutic strategies targeting components of the …

Association Of Statin Use On Survival Outcomes Of Patients With Early-Stage Her2-Positive Breast Cancer In The Aphinity Trial, Christian Maurer, Elisa Agostinetto, Lieveke Ameye, Matteo Lambertini, Samuel Martel, Noam Ponde, Mariana Brandão, Francesca Poggio, Arlindo Ferreira, Rachel Schiff, Carmine De Angelis, Richard D Gelber, Susan Dent, Christoph Thomssen, Martine Piccart, Evandro De Azambuja

Faculty, Staff and Students Publications

Purpose: There is evidence that statins might improve the outcome of patients with breast cancer. The role of statins in patients with early HER2-positive breast cancer is unknown. Therefore, we explored the association between statin use and survival outcomes in early HER2-positive breast cancer patients in the phase III APHINITY trial (adjuvant pertuzumab/trastuzumab).

Methods: All patients (intent-to-treat population, n = 4804) were included (6.2 years median follow-up database). The primary objective was to investigate the association of statin use on invasive disease-free survival (IDFS), distant relapse-free interval (DRFI), and overall survival (OS). Patients who received statins at baseline, or started …

Comparison Of Energy Efficiency And Vegetation In Different Establishment And Management Systems Of Steep Mountainous Grassland In The Aso Area, Japan, K Kabata, C Okamoto, M Shimizu, M Kikuchi

IGC Proceedings (1977-2023)

The Aso area is one of the most important areas for grass­land agriculture in Japan. In this area there exists ca. 44,000 hectares of which ca. 28,700 ha are steep mountainous lands ( a gradient of more than 15 degrees). Additionally, there is much precipitation (ca 2.600 mm/year) in the area. Consequently, there is a problem of grassland destruction due to soil erosion. Therefore, in order to promote the utilization and conser­vation of steep grasslands, the following two experimental grazing were carried out: 1) a two pasture system and 2) a coexistent pasture system with introduced and native grasses. In …

Comparison De La Dynamique De La Vegetation De Deux Ecosystemes Herbagers Mesoxerophiles Apres Deprise Agricole Dans Le Massif Vosgien, S Muller

IGC Proceedings (1977-2023)

Les orientations actuelles de !'agriculture europeenne dans le cadre de la Politique Agricole Commune de la Communaute Economique Europeenne devraient conduire a !'abandon dans les decennies a venir de plusieurs millions d'hectares de terres agricoles en France, entrainant des modifications ecologiques et paysageres considerables. Dans le Massif Vosgien la deprise agricole, consecutive a la regression des industries traditionnelles et a !'elevation du niveau de vie, a provoque !'abandon depuis les annees 1950 de nombreux herbages, autrefois entretenus surtout par des pluri­actifs. Ces milieux evoluent alors vers des friches herbacees seboisant plus ou moins rapidement de maniere spontanee.

Massif Vosgien constitue …