Medicine and Health Sciences Commons^™

Movement-Stabilized Three-Dimensional Optical Recordings Of Membrane Potential Changes And Calcium Dynamics In Hippocampal Ca1 Dendrites, Kevin C Gonzalez, Satoshi Terada, Asako Noguchi, George N Zakka, Cliodhna O'Toole, Giuliana Bilbao, Luke Reynolds, Anna Jász, Borbála Kertész, Zoltán Szadai, Alissa Shen, François St-Pierre, Franck Polleux, Attila Losonczy, Balázs Rózsa

Faculty, Staff and Students Publications

Local dendritic computations are thought to critically influence neuronal signaling and plasticity yet remain largely unexplored in vivo due to challenges in stably imaging small structures at ultrafast timescales. We developed a 3D real-time motion correction platform for movement-stabilized, ultrafast two-photon voltage imaging. By co-labeling CA1 pyramidal neurons with voltage and calcium indicators, we simultaneously measured somato-dendritic and electro-calcium coupling at multiple dendritic sites. We characterized isolated dendritic spikes and distance-dependent backpropagation of naturally occurring and photostimulation-evoked bursts and single spikes. We found that bursts backpropagated more reliably than single spikes, validated that somato-dendritic coupling decreases with distance from soma, …

Cardiac Hdac3 Disruption Contributes To Hdac Inhibitor-Induced Qt Prolongation, Jiao Lu, Christopher Ward, Sichong Qian, Lilei Zhang, Jiang Chang, Zheng Sun

Faculty, Staff and Students Publications

Histone deacetylase (HDAC) inhibitors are approved for cancer treatment and are being investigated for a wide range of other diseases. Despite their therapeutic promise, clinical studies have reported cardiac side effects, particularly electrocardiogram (EKG) abnormalities, with QT interval prolongation being one of the most consistently reported findings. The mechanisms underlying these cardiac effects remain unclear. In this study, we investigated the role of HDAC3 in cardiac electrophysiology. We found that postnatal depletion of cardiac HDAC3 in mice caused QT interval prolongation, recapitulating the EKG abnormalities reported with HDAC inhibitor use. Adult-onset inducible depletion of cardiac HDAC3 induced additional EKG abnormalities, …

Wnt-Dependent Ontogeny Of Acellular Cementum-Forming Cementoblasts On The Tooth Root Surface, Taishi Komori, Mizuki Nagata, Natnicha Praneetpong, Hanwen Fan, Yuxiao Zhou, Noriaki Ono, Wanida Ono

Faculty, Staff and Student Publications

Cementum is a specialized mineralized tissue that covers the tooth root surface and anchors the tooth to the surrounding periodontal ligament. The cervical acellular cementum (AC) is indispensable for periodontal attachment and represents a key target for periodontal regenerative therapies. However, the developmental origin and molecular identity of AC-forming cementoblasts remain poorly understood. Here, through an integrated spatial and single-cell transcriptomic analysis, we identify AC-forming cementoblasts as a distinct population of noncanonical mineralizing cells enriched for cell-matrix organization and Wnt signaling signatures, distinguishing them from cellular cementum-forming cementoblasts localized in the apical portion. Lineage tracing using a Wnt inhibitory factor …

Selective And Differential Roles Of Pvhcrh Neurotransmitters In Diet-Induced Obesity In Mice, Zhiying Jiang, Yuhan Cao, Michelle He, Cunjin Su, Runzhou Yang, Maojie Yang, Jing Cai, Hongli Li, Yuanzhong Xu, Shi-Bin Li, Hiroshi Yamaguchi, Luis De Lecea, Benjamin R Arenkiel, Qingchun Tong

The Brown Foundation: Institute of Molecular Medicine

Stress and diet are known to synergistically promote risks of obesity but the underlying neural basis remains elusive. Corticotropin-releasing hormone neurons in the paraventricular hypothalamus (PVHCRH) are stress responsive and release both CRH and glutamate. Here we generated a mouse model with gain or loss of release in CRH or glutamate from PVHCRH neurons. While these models showed no changes in body weight when fed chow, they exhibited contrasting effects when fed high-fat high-caloric diets (HFD). Whereas disrupting glutamate release from PVHCRH neurons led to diet-induced obesity (DIO), that of CRH caused no impact. Conversely, augmented CRH release led to …

Abl Kinases Regulate Fgf Signaling Independent Of Crk Phosphorylation To Prevent Peters Anomaly Type Ii, Hao Wu, Yingyu Mao, Qian Wang, Honglian Yu, Michael Bouaziz, Neoklis Makrides, Enpeng Wang, Zhipeng Ding, Anthony J Koleske, Glenn L Radice, Jerry Hsu, Xin Zhang

2020-Current year OA Pubs

Peters anomaly is an anterior segment dysgenesis and a leading cause of congenital corneal opacity. Here, we show that loss of ABL kinases restores lens induction in the absence of FGF signaling but induces Peters anomaly type II independently of ERK signaling, a phenotype also observed with elevated FGF-Ras activity. This defect is rescued by allelic deletion of the ABL substrates CRK and CRKL. Contrary to prevailing models, ABL kinases do not act through direct phosphorylation of CRK proteins; instead, they phosphorylate PTPN12, suppressing p130CAS phosphorylation and CRK recruitment required for RHO GTPase activation. ABL kinase deficiency reduces actomyosin contractility …

Type-1 Ryanodine Receptor Plays An Important Role In Cardiac Hypertrophy And Heart Failure By Increasing Type-2 Ryanodine Receptor-Mediated Calcium Release, Yong-Xiao Wang, Ed Wilson Santos, Sarahann Mistretta, Yuexing Yuan, Harold A. Singer, Shey-Shing Sheu, Yun-Min Zheng

Center for Translational Medicine Faculty Papers

Type-1 ryanodine receptor (RyR1) is essential for skeletal muscle contraction. This Ca²⁺ release channel is expressed in cardiac myocytes; however, its function remains elusive. Cardiac-specific RyR1 overexpression (OE) mice were generated under the cardiac-specific Myh6 promoter. Cardiac hypertrophy (CH), cardiac functions, and mechanistic changes in RyR1 OE and control (wildtype, WT) mice were assessed using hematoxylin and eosin staining, echocardiography, electrocardiogram, quantitative RT-PCR, Western blotting, [³H]-ryanodine binding assay, confocal microscope, ROS dye Amplex Red and 2′,7′-dichlorofluorescein diacetate. RyR1 OE mice had increased whole heart, left ventricular weight, and left ventricular wall thickness, but decreased cardiac output and …

Volume Electron Microscopy Reveals Heterogeneity Of The Hemostatic Response In Veins And Arteries, Maurizio Tomaiuolo, Meghan E. Roberts, Jenna R. Severa, Christopher D. Mansi, Brenna B. Y. Mathers, Anna Mannix, Trace A Christensen, Lawrence F Brass, Talid Sinno, Timothy J. Stalker

Cardeza Foundation for Hematologic Research

Intravital imaging studies have provided insights into the spatial and temporal variations of platelet activation and thrombin generation that occur during hemostasis; however, these studies are generally limited to small vessels due to the practical limitations of imaging in thicker tissues. Recent advances in cleared tissue fluorescence imaging as well as volume electron microscopy (vEM) coupled with machine learning-based image segmentation provide an opportunity for analysis of the 3-dimensional structure of complex tissues. We utilized these technologies to examine hemostatic plugs from murine jugular veins and carotid arteries to investigate the spatial distribution of platelet activation and biochemical responses in …

Water-Soluble Fullerene Derivatives Mitigate Cranial Radiation-Induced Neuroinflammation And Cognitive Dysfunction, Naren Gundapaneni, Iona Hill, Lydia W T Cheung, Khadijeh Koushki, Alyssa Fausnaught, Phuoc Minh Quan Mai, Arjun Vasan, Prapannajeet Biswal, Ashutosh Tripathi, Anilkumar Pillai, Vijayasree V Giridharan, Tatiana Barichello, Yuri Mackeyev, Sunil Krishnan

Faculty, Staff and Student Publications

Radiotherapy is widely used to treat malignant and benign brain tumors. A major constraint, however, is the low tolerance of normal brain tissue to radiation. Cranial irradiation-induced injury manifests as inflammatory responses and neurodegeneration, which jointly contribute to progressive cognitive decline. These complications can restrict the delivery of optimal therapeutic doses, cause persistent neurological symptoms, and ultimately compromise quality of life. Thus, neuroprotective agents have emerged as a strategy to safeguard normal tissues from radiation-induced neurotoxicity. This study investigated the efficacy of a highly soluble [60]fullerene (C60) derivative, C60-ser, a carbon-based nanomaterial, to mitigate radiation-induced brain injury. Oral administration of …

Progressive Cardiac Phenotypes And Reduced Reversibility From Long-Term Cugexp Rna Expression In A Dm1 Mouse Model, Rong-Chi Hu, Mohammadreza Tabary, Xander Ht Wehrens, Thomas A Cooper

Faculty, Staff and Students Publications

Myotonic dystrophy type 1 (DM1) is caused by an expanded CTG repeat in the DMPK gene, resulting in mutant transcripts that form expanded CUG (CUGexp) RNA foci and sequester muscleblind-like (MBNL) RNA-binding proteins. DM1 is multisystemic, with progressive worsening of disease manifestations in affected tissues. Disease progression is attributed to somatic expansion of the CTG repeats with age, resulting in production of CUGexp RNA with enhanced intrinsic toxicity due to increased MBNL sequestration. To determine the degree to which cardiac disease progression can occur independently of repeat expansion, we used a transgenic DM1 mouse model with inducible heart-specific expression of …

Tunable Tripcides Suppress Virulence Factor Secretion During Staphylococcus Aureus Infection And Kill Dormant Cells, Hasan Tükenmez, Taylor M Nye, Suzanne Hickerson, Chloe L P Obernuefemann, Jerome S Pinkner, Karen W Dodson, Michael G Caparon, Scott J Hultgren, Et Al.

2020-Current year OA Pubs

Antimicrobial resistance (AMR) in common bacterial pathogens, including methicillin-resistant

Genetic Analysis Of The X-Linked Adrenoleukodystrophy Gene Abcd1 In Drosophila Uncovers A Conserved Phenotype, Joshua Manor, Sharayu V Jangam, Hyung-Lok Chung, Pranjali Bhagwat, Jonathan C Andrews, Hillary Chester, Shu Kondo, Saurabh Srivastav, Juan Botas, Ann B Moser, Suzette M Huguenin, Michael F Wangler

Duncan NRI Faculty and Staff Publications

X-linked adrenoleukodystrophy (X-ALD) is a progressive neurodegenerative disorder caused by a loss-of-function (LOF) mutation in the ATP-binding cassette subfamily D member 1 (ABCD1) gene, leading to the accumulation of very long-chain fatty acids (VLCFAs). This disorder exhibits striking heterogeneity; some male patients develop an early childhood neuroinflammatory demyelination disorder, while other patients, including adult males and most affected female carriers, experience a chronic progressive myelopathy. Adrenocortical failure is observed in almost all male patients, with the age of onset varying, sometimes being the first diagnostic finding. The gene underlying this spectrum of disease encodes an ATP-binding cassette (ABC) transporter that …

Gut Microbiota Modulation Of Regulatory Dna Elements Revealed By Massively Parallel Functional Characterization, Chadmirah Zaratiana, Adheet Ganesh, Yang E Li, Et Al.

2020-Current year OA Pubs

Cis-regulatory elements (CREs) are central to dynamic gene regulation in hepatocytes, yet most functional annotations derive from in vitro models that poorly capture physiological regulation. We systematically profiled 109,386 human liver-derived CREs using massively parallel reporter assays in hepatocytes under matched in vitro and in vivo conditions. In vivo-active functional CREs (fCREs) were enriched for H3K27ac and chromatin accessibility and were regulated by diverse transcription factors in the human liver. We further demonstrate that gut microbiota-derived signals modulate fCRE activity and target gene expression in vivo, in part via the KEAP1/NFE2L2 antioxidant pathway. Specific microbial metabolites directly altered the activity …

Cd8+ T Cell Differentiation Into Nk-Like Effector Cells Drives Transplant Rejection, Dawei Zou, Stephanie G Yi, Yulin Dai, Luan Truong, Lillian W Gaber, Richard J Knight, Xiang Xiao, Rafik M Ghobrial, Xian C Li, Zhongming Zhao, Wenhao Chen, A Osama Gaber

Faculty, Staff and Student Publications

T cells are central drivers of transplant rejection, yet the differentiation fates underlying this process remain unclear. Using single-cell transcriptomic profiling of human kidney allograft biopsies, we identified a predominant infiltrating CD8+ T cell subset exhibiting killer cell lectin-like receptor (KLR)+ NK-like features. Mechanistic studies in mice showed that the KLR+ subset emerged de novo post-transplantation and dominated the CD8+ T cell infiltrate in rejecting allografts. These NK-like CD8+ T cells expressed high levels of interferon regulatory factor 4 (IRF4), and Irf4 deletion disrupted their differentiation and induced transplant acceptance. Therapeutically, either costimulation blockade or mTOR inhibition substantially reduced the …

+Cd49a+Cd103+ Cytotoxic Tissue-Resident Natural Killer Cells Infiltrate And Control Solid Epithelial Tumor Growth In Mice, Nina B Horowitz, Jennifer A Foltz, Et Al.

2020-Current year OA Pubs

Human tissue-resident natural killer (NK) cells (trNK cells), broadly defined by markers of tissue residency, such as CD49a [

Early-Life Wnt4 Expressing Colon Stromal Cells Orchestrate Lifelong Mucosal Homeostasis Via Bmp-Driven Inkt Cell Imprinting, Xi Lin, Chloe Hyun-Jung Lee, Ting Zhang, Agne Antanaviciute, Thomas Hanley, Jonathan N Glickman, Nikhila S Bharadwaj, Vicki Rosen, Jenny E Gumperz, Matthew K Waldor, Alison Simmons, Thomas Gensollen, Richard S Blumberg

2020-Current year OA Pubs

The early-life intestinal microenvironment plays a pivotal role in shaping immune cell development. Here, we identify a colonic Wnt4-expressing stromal cell, enriched during early-life, that promotes iNKT cell proliferation via BMP-MAPK signaling. These stromal cells are spatially associated with iNKT cells and macrophages and exhibit high Bmp2 expression during the neonatal period. Depletion of BMP2 in Wnt4

Mitochondrial Etf Insufficiency Drives Neoplastic Growth By Selectively Optimizing Cancer Bioenergetics, David Papadopoli, Sergej Djuranovic, Et Al.

2020-Current year OA Pubs

Mitochondrial electron transport flavoprotein (ETF) insufficiency causes metabolic diseases known as a multiple acyl-CoA dehydrogenase deficiency (MADD). In contrast to muscle, ETFDH is a non-essential gene in acute lymphoblastic leukemia NALM6 cells, and its expression is reduced across human cancers. In various human cancer cell lines and mouse models, ETF insufficiency caused by decreased ETFDH expression limits flexibility of OXPHOS fuel utilisation but paradoxically increases bioenergetics and accelerates neoplastic growth via activation of the mTORC1/BCL-6/4E-BP1 axis. Collectively, these findings reveal that while ETF insufficiency is rare and has detrimental effects in non-malignant tissues, it is common in neoplasia, where ETFDH …

Purine Metabolic Adaptation Protects The Endothelium From Disturbed Flow-Induced Dna Damage And Atherosclerosis, Qian Ma, Yongfeng Cai, Zhidan Zhang, Dingwei Zhao, Yuan Zhao, Peishan Xu, Tammy Lu, Wendy Zhang, Qiuhua Yang, Yaqi Zhou, Varadarajan Sudhahar, Tohru Fukai, Hanjoong Jo, Yiming Xu, Yuqing Huo

Faculty, Staff and Students Publications

Despite effective lipid-lowering therapies, atherosclerosis continues to be a leading cause of death, with considerable residual cardiovascular risk. Atherosclerotic lesions develop preferentially at arterial regions exposed to disturbed flow (d-flow), which induces genomic stress, endothelial injury, and barrier dysfunction. Hemodynamic forces are known to reprogram endothelial metabolism, but the role of de novo purine synthesis (DNPS), which supplies nucleotides for genome maintenance and whose terminal steps are catalyzed by the bifunctional enzyme ATIC, remains undefined in atherosclerosis. By integrating bulk and single-cell multiomics with in vitro flow systems and in vivo models, we show that d-flow upregulates DNPS and ATIC …

Logistic Regression For Estimating Functional Effects With Spatial Transcriptomics, Michael Barkasi, Cody Nhan Pham, Demetrios Neophytou, Hysell V Oviedo

2020-Current year OA Pubs

Spatial transcriptomics (ST) unlocks potential for studying gene functions in processes that depend on orchestration of transcription across space. However, analysis tools for ST remain aimed at data exploration, with few resources for hypothesis testing. What's missing is a way to test whether a factor of interest affects functionally relevant parameters of a gene's spatial distribution. We present a tool to fill this gap, which we call a warped sigmoidal Poisson-process mixed-effects (WSP, pronounced "wisp") model. WSP models are the first ST tool allowing researchers to test critical questions without bespoke preprocessing pipelines for identifying key spatial parameters. By aligning …

Syrah: A Pipeline To Maximize Spatial Transcriptomics Data Output, Carolyn Brewster, Frederick G Mann, Blair Benham-Pyle, Alejandro Sánchez Alvarado

Faculty, Staff and Students Publications

Spatial analysis of gene expression patterns has been a key technique for revealing the potential functions of genes. Traditionally, these analyses conducted using in-situ hybridizations and other labor-intensive protocols were constrained to examining only a few candidate genes per sample. However, the advent of spatial transcriptomic techniques like Slide-seqV2 has transformed this field, enabling massively parallel exploration of gene expression patterns within their tissue contexts by pairing spatial locations with RNA sequencing. Despite its potential, Slide-seqV2 datasets often produce fewer usable reads than expected. We have identified that a significant source of errors in the technology stems from the chemical …

Antibody-Drug Conjugates Beyond Her2 In Non-Small Cell Lung Cancer (Nsclc): Mechanisms, Emerging Targets, And Future Directions., Ahmed Ismail, Aakash Desai, George R Simon, Yanis Boumber

Oncology Articles

Antibody-drug conjugates (ADCs) are a rapidly evolving class of oncology therapeutics that enable precise delivery of potent cytotoxic agents to tumor cells while minimizing systemic toxicity. While HER2-targeted ADCs such as trastuzumab deruxtecan (T-DXd) in HER2-mutant, Datopotamab deruxtecan (Dato-Dxd) in EGFR-mutant, and telisotumumab vedotin (Teliso-V) in MET IHC 3+ expressing lung cancer have already established a clinical role in non-small cell lung cancer (NSCLC), multiple ADCs targeting alternative antigens, including additional TROP2 ADCs, HER3, MET, CEACAM5, B7-H3, Nectin-4, and others, are now in advanced clinical development. This review synthesizes the current evidence for non-HER2 ADCs in NSCLC, highlighting mechanisms of …

Androgen Loss Accelerates Brain Tumour Growth Via Hpa Axis Activation, Juyeun Lee, Joshua B Rubin, Et Al.

2020-Current year OA Pubs

Many cancers, including glioblastoma (GBM), show a male-biased incidence and associated worse outcomes

Plasma Constituents Promote Endothelial Thromboinflammatory Dysfunction After Hemorrhagic Shock, Kelly E Sanders, Marissa D Pokharel, Baron K Osborn, Yao-Wei Wang, Charles E Wade, Lucy Z Kornblith, Mitchell J Cohen, Jessica C Cardenas

Faculty, Staff and Student Publications

Background: Hemorrhagic shock (HS) following traumatic injury is hallmarked by innate immune activation, hypercoagulability, and thromboinflammatory complications. To date, the direct link between HS, injury severity, and endothelial cell (EC) contributions to thromboinflammation remains poorly understood. The goals of this study were to determine the impact of injury severity and HS on endothelial-mediated thromboinflammation and examine whether these changes increase the propensity for thrombosis.

Methods: Plasma from 89 male trauma patients, stratified by HS and injury severity, and 10 healthy subjects were assessed for inflammatory mediators by BioPlex. Human lung microvascular endothelial cells were exposed to patient plasma for 4 …

Ixodid And Flea Infestations And Associated Bacteria On Two Sympatric Felid Species In South Texas, Allan T Showler, Hilary Swarts, Maya Murry, Alisa Nelson, Alexander R Kneubehl, Sarah M Gunter

Faculty, Staff and Students Publications

Ixodid ticks and fleas parasitize wild felids and can transmit pathogens of veterinary and public health concern. We identified ixodid and flea species collected from sympatric South Texas bobcats, L. rufus, and ocelots, L. pardalis. Greater diversities of ixodids were found on both felids than in previous reports, with seven species in three genera on L. rufus and six species in three genera on L. pardalis. We report first findings of tropical horse tick, Dermacentor nitens, on L. rufus in Texas, and Ixodes keiransi on both felids in Texas. Although false cayenne tick, Amblyomma tenellum, nymphs were the most abundant …

Hiding In Plain Sight: A Call To Prevent Cutaneous Leishmaniasis Transmission In The United States, Juan David Ramírez, Sarah M Gunter, Megan Coffee, Norman Beatty, Dawn M Wetzel

Faculty, Staff and Students Publications

Cutaneous leishmaniasis (CL), once considered a travel-associated tropical disease, is increasingly transmitted within the United States, particularly in southern regions. Despite mounting evidence of local transmission, public health recognition and preventive infrastructure remain limited. This Viewpoint highlights the urgent need to shift the U.S. CL response from questioning endemicity to preventing transmission. We review ecological, clinical, and surveillance data demonstrating the presence of competent vectors, animal reservoirs, and autochthonous human cases. Diagnostic delays, underreporting, and insufficient provider training contribute to missed prevention opportunities. Climate change and peri-urban rodent-human contact data further heighten future risk. A coordinated response is essential, including …

Adhesion G Protein-Coupled Receptors, Tobias Langenhan, Garret R Anderson, Demet Araç, Gabriela Aust, Monserrat Avila-Zozaya, Sofie Morsing Bagger, Patrick Barth, Sandra Berndt, Stephen C Blacklow, Beatriz Blanco-Redondo, Antony A Boucard, James P Bridges, Lara-Sophie Brodmerkel, Kathleen M Caron, Yin Kwan Chung, Andrew N Dates, Virginea De Araujo Farias, Daniel Del Toro, Joseph G Duman, Felix B Engel, David M Favara, Caroline J Formstone, Chaoyu Fu, Alain Garcia De Las Bayonas, Anastasia Georgiadi, David E Gloriam, Randy A Hall, Jörg Hamann, Peter W Hildebrand, Cheng-Chih Hsiao, Bill X Huang, Jonathan A Javitch, Hee-Yong Kim, Robert J Kittel, Gunnar Kleinau, Richard Leduc, Ines Liebscher, Hsi-Hsien Lin, Joshua Linnert, Marie-Gabrielle Ludwig, David C Martinelli, Signe Mathiasen, Daniel Matúš, Mariam Melkumyan, Ana L Moreno-Salinas, Jan Mulder, Michael A Nash, Kasturi Pal, Daniel T Pederick, Nicole A Perry-Hauser, Xianhua Piao, Yu-Qi Ping, Dimitris G Placantonakis, Fabian Pohl, Simone Prömel, Mette M Rosenkilde, Laurent Sabbagh, Richard C Sando, Patrick Scheerer, Torsten Schöneberg, Elena Seiradake, Mareike Selcho, Florian Seufert, Abhishek K Singh, Georgios Skiniotis, Katja Spiess, Norbert Sträter, David Strutt, Thomas C Südhof, Jinpeng Sun, Gregory G Tall, Doreen Thor, Douglas G Tilley, Kimberley F Tolias, Mario Vallon, Erwin G Van Meir, Benoit Vanhollebeke, Giselle R Wiggin, Uwe Wolfrum, Jie Yan, Nathan A Zaidman, Yimin Zou, Nicole Scholz

Faculty, Staff and Students Publications

Adhesion G protein-coupled receptors (aGPCRs) constitute a structurally and functionally distinct group within the superfamily of GPCRs. In 2015, the International Union of Pharmacology invited the Adhesion GPCR Consortium to publish a comprehensive review about aGPCRs and establish a unified nomenclature. Since then, substantial progress has been made in delineating the biological roles, molecular architecture, biochemical properties, expression profiles, ligand repertoire, and activation and signaling strategies of aGPCRs. Commensurate with these advances, their relevance to human pathophysiology has become increasingly apparent. In a coordinated effort, the Adhesion GPCR Consortium has reviewed recent progress in this field and provides a comprehensive …

Adhesion G Protein-Coupled Receptors, Tobias Langenhan, Garret R Anderson, Demet Araç, Gabriela Aust, Monserrat Avila-Zozaya, Sofie Morsing Bagger, Patrick Barth, Sandra Berndt, Stephen C Blacklow, Beatriz Blanco-Redondo, Antony A Boucard, James P Bridges, Lara-Sophie Brodmerkel, Kathleen M Caron, Yin Kwan Chung, Andrew N Dates, Virginea De Araujo Farias, Daniel Del Toro, Joseph G Duman, Felix B Engel, David M Favara, Caroline J Formstone, Chaoyu Fu, Alain Garcia De Las Bayonas, Anastasia Georgiadi, David E Gloriam, Randy A Hall, Jörg Hamann, Peter W Hildebrand, Cheng-Chih Hsiao, Bill X Huang, Jonathan A Javitch, Hee-Yong Kim, Robert J Kittel, Gunnar Kleinau, Richard Leduc, Ines Liebscher, Hsi-Hsien Lin, Joshua Linnert, Marie-Gabrielle Ludwig, David C Martinelli, Signe Mathiasen, Daniel Matúš, Mariam Melkumyan, Ana L Moreno-Salinas, Jan Mulder, Michael A Nash, Kasturi Pal, Daniel T Pederick, Nicole A Perry-Hauser, Xianhua Piao, Yu-Qi Ping, Dimitris G Placantonakis, Fabian Pohl, Simone Prömel, Mette M Rosenkilde, Laurent Sabbagh, Richard C Sando, Patrick Scheerer, Torsten Schöneberg, Elena Seiradake, Mareike Selcho, Florian Seufert, Abhishek K Singh, Georgios Skiniotis, Katja Spiess, Norbert Sträter, David Strutt, Thomas C Südhof, Jinpeng Sun, Gregory G Tall, Doreen Thor, Douglas G Tilley, Kimberley F Tolias, Mario Vallon, Erwin G Van Meir, Benoit Vanhollebeke, Giselle R Wiggin, Uwe Wolfrum, Jie Yan, Nathan A Zaidman, Yimin Zou, Nicole Scholz

Faculty, Staff and Students Publications

Adhesion G protein-coupled receptors (aGPCRs) constitute a structurally and functionally distinct group within the superfamily of GPCRs. In 2015, the International Union of Pharmacology invited the Adhesion GPCR Consortium to publish a comprehensive review about aGPCRs and establish a unified nomenclature. Since then, substantial progress has been made in delineating the biological roles, molecular architecture, biochemical properties, expression profiles, ligand repertoire, and activation and signaling strategies of aGPCRs. Commensurate with these advances, their relevance to human pathophysiology has become increasingly apparent. In a coordinated effort, the Adhesion GPCR Consortium has reviewed recent progress in this field and provides a comprehensive …

A Scoping Review Of The Associations Between Ascariasis, Helicobacter Pylori Infection And Gastric Pathologies, Nina L Tang, Jacob J Williams, Jennifer Stockton, Maria Elena Bottazzi, Jill E Weatherhead

Library Staff Publications

Ascaris infection-ascariasis-is the most common human parasitic worm infection worldwide and induces damage and cellular changes within the stomach. Helicobacter pylori is a bacterium of the stomach that also causes gastric pathologies globally. Importantly, Ascaris, H. pylori, and gastric diseases all disproportionately affect individuals in resource-limited settings. However, the associations between ascariasis, H. pylori infection, and gastric diseases remain relatively unexplored. We synthesized the existing research associating Ascaris infection with H. pylori infection and/or gastric pathologies. Records were identified in OVID Medline, Embase and Web of Science using search terms for ascariasis, H. pylori infection, and gastric abnormalities and additional …

Noncanonical Clock Regulators Control Stress Responses In Digestive Diseases, Dishu Zhou, Roberto E López-Valiente, Samer G Mattar, Dongyin Guan

Faculty, Staff and Students Publications

The digestive system is essential for nutrient absorption, processing, and waste elimination. The expression of many genes and physiological processes within this system exhibits a 24-h rhythmicity. However, modern lifestyle factors, such as jet lag, shift work, and irregular eating patterns, significantly disrupt these rhythms, triggering various stress responses and contributing to numerous digestive disorders. Here, we focus on emerging studies on noncanonical clock regulators involved in stress responses, integrate these novel findings into the established model of the core circadian clock, and highlight recent advances in the development of novel therapeutics targeting these 24-h regulators. In addition, we discuss …

Natural Maternal Immunity Protects Neonates From Escherichia Coli Sepsis., Raymond E. Diep, Ujjwal Adhikari, Kubra Gokce Tezel, Giang Pham, Allison R. Burrell, Mary A. Staat, Nguyen Thi Khanh Nhu, Minh-Duy Phan, Kate M. Peters, Mark A. Schembri, Scott H. Saunders, David B. Haslam, John J. Erickson, Susana Chavez-Bueno, Sing Sing Way

Manuscripts, Articles, Book Chapters and Other Papers

Escherichia coli is a leading cause of neonatal sepsis, with infection occurring in approximately one in every 1,000 live births. However, with E. coli colonization beginning soon after birth and defects in neonatal host defence maturation, an alternative consideration is why infection does not occur even more frequently. Here we show that newborn babies with E. coli sepsis have selectively reduced vertically transferred natural antibodies that recognize E. coli, mechanistically explaining their susceptibility to infection. Complementary preclinical studies show that preconceptual intestinal colonization with probiotic E. coli Nissle 1917 (EcN) primes anti-E. coli immunoglobulin G (IgG) antibodies with broad cross-reactivity …

Fructose: Metabolic Signal And Modern Hazard, Richard J Johnson, Miguel A Lanaspa, Dean R Tolan, Marcus D Goncalves, Samir Softic, Kimber L Stanhope, Laura G Sánchez-Lozada, Mark A Herman, Joshua D Rabinowitz

Faculty, Staff and Students Publications

There is much interest in the role of sweeteners such as table sugar (sucrose) and high-fructose corn syrup in obesity and metabolic disease. Both sweeteners consist of glucose and fructose, two six-carbon isomeric sugars. Whereas glucose ingestion may promote obesity through its effects to stimulate insulin secretion, fructose has unique metabolic effects that promote triglyceride synthesis and fat accumulation. These effects arise from fructose's well-known role as a signal of metabolic plenty. Under modern conditions of overnutrition, chronic excess fructose drives features of metabolic syndrome. Emerging evidence further links fructose to cancer and dementia. Here we review the biochemical, molecular …