Digital Commons Network^™

Quantitative Assessment Of Cardiac Phosphocreatine Metabolism Under Physiological And Pharmacological Stress Using Chemical Exchange Saturation Transfer Magnetic Resonance Imaging, Qi Huang, Caleb Berberet, Ryan Wahidi, Todd Pavek, Cihat Eldeniz, Liya Dai, Rong Guo, Yang Yang, Scott Bugenhagen, Linda R Peterson, Thomas H Schindler, Pamela K Woodard, Jie Zheng

2020-Current year OA Pubs

BACKGROUND: Phosphocreatine (PCr) exhibits a distinct chemical exchange saturation transfer (CEST) resonance at ∼2.5 ppm with slower exchange kinetics and lower pH sensitivity than creatine. This pilot study evaluated the feasibility of quantifying myocardial PCr-dominated concentration ([PCr]

METHODS: Phantoms with varied concentrations of PCr and Cr were scanned to characterize PCr CEST signals under physiological conditions. Experiments were conducted at both room temperature and 37 °C with full Z-spectra acquisition. For the study in vivo, CEST imaging was performed in normal canines (n = 13), at rest and after regadenoson vasodilation, and during dobutamine stress (n = 5). In addition, …

Spatial Transcriptomic Profiling Of Decalcified Murine Musculoskeletal Samples Via Xenium Prime 5k, Lindsey Lammlin, Huong X Tran, Aanya Mohan, Michael D Newton, Scarlet C Howser, Stephen J Redding, Christina A Capobianco, Kurt D Hankenson, Alexander J Knights, Tristan Maerz

2020-Current year OA Pubs

Successful generation of high-quality spatial transcriptomics data from murine musculoskeletal tissues has been impeded by the challenge of preserving RNA integrity through the harsh tissue processing steps required for histological sectioning. In particular, the need to thoroughly fix and decalcify mineralized tissues has proven problematic. We detail a comprehensive sample processing pipeline for 3 common murine musculoskeletal tissue samples, enabling high-quality transcript detection via imaging-based spatial transcriptomics using the Xenium Prime 5K platform from 10x Genomics. Our protocol outlines methodological details for transcardiac perfusion, fixation, decalcification, paraffin processing, and a sample co-embedding strategy facilitating anatomically consistent and simultaneous sectioning of …

Neural Plasticity Across Hormonal States In Females: From Modulator To Dynamic Regulator, Takahiro Sasaki, Christine Nwaigwe, Sayaka Inoue

2020-Current year OA Pubs

Ovarian sex steroid hormones play a critical role in regulating fertility. In addition, these hormones influence behavior and mood across the lifespan in females. Converging evidence from rodent studies and human neuroimaging shows that ovarian hormones dynamically regulate neuronal excitability, synaptic efficacy, and structural remodeling across menstrual/estrous cycles, puberty, and reproductive aging. Estrogen and progesterone reorganize network dynamics and gate plasticity eligibility rather than uniformly scaling synaptic strength, with additional contributions from glia, the extracellular matrix, and neurosteroid signaling. Here we synthesize recent cross-scale advances that link structural and functional changes to cellular and circuit mechanisms, and relate these dynamics …

Role Of Households With Children In Community Spread Of Multidrug-Resistant Enterobacterales, St. Louis, Missouri, Usa, Barrett Breeze, Ahmed Babiker, Sreenivas Konda, Alaina L Robinson, Stefan J Green, Catherine C Babbs, Federico Cunha, Katherine Y Shen, India Shepherd Hammond, Stephanie A Fritz, Latania K Logan

2020-Current year OA Pubs

Community-acquired multidrug-resistant (MDR) Enterobacterales bacteria are an increasing public health concern, yet whether households play a role in community spread remains unclear. We investigated 150 households with children in St. Louis, Missouri, USA, for MDR Enterobacterales. We cultured swab specimens from household members and environmental surfaces for identification and antimicrobial susceptibility testing. We also performed whole-genome sequencing in the 53 (35%) households where >1 MDR Enterobacterales species were recovered. Enterobacter hormaechei predominated, followed by Klebsiella pneumoniae and Pantoea species. Whole-genome sequencing revealed closely related strains shared between persons and environmental surfaces, suggesting potential intra-household transmission. We identified >1 horizontal gene …

Rapid Antidepressant Potential Of Nitrous Oxide: Current State And Major Questions, Charles F Zorumski, Joseph Cichon, Yukitoshi Izumi, Thomas Zeffiro, Steven Mennerick, Peter Nagele, Charles R Conway

2020-Current year OA Pubs

The success of ketamine, a dissociative anesthetic and non-competitive N-methyl-D-aspartate receptor (NMDAR) antagonist, as a rapidly acting antidepressant has ignited efforts to identify other novel depression treatments. In recent years, several clinical trials indicated that nitrous oxide (N

Viscoelastic And Morphologic Changes In The Lumbar Intervertebral Discs Of The 5xfad Mouse Model Of Alzheimer's Disease, C E Gonzalez, C A Schurman, K A Wilson, B Schilling, L M Ellerby, S Y Tang

2020-Current year OA Pubs

BACKGROUND: Chronic low back pain, commonly associated with intervertebral disc (IVD) degeneration, is highly prevalent in patients with Alzheimer's disease (AD), and the severity of the pain is correlated with the severity of the dementia. While incidences of both afflictions increase dramatically in the elderly population, it is unknown whether AD exacerbates the health of the IVD.

AIMS: The aim of this study is to examine how AD-related mutations affect the structure and mechanics of the IVD.

MATERIALS AND METHODS: Utilizing one-year-old male and female 5xFAD mice that constitutively express human APP and PSEN1 transgenes with five AD-linked mutations, we …

Inflammaging In Aged Tissues Drives Remodeling Of The Cd8+ T Cell Compartment, Irina Shchukina, Carlos J Rodriguez-Hernandez, Heather S Ruiz, Maksim Kleverov, Rachel L Mintz, Katsutaka Mineura, Subhadra C Gunawardana, Sunnie Hsiung, Bishan Bhattarai, Veronika Vachova, Jan Kossl, Denis A Mogilenko, Rachael L Field, Tran H Nguyen, Quazim A Alayo, Christopher G Huckstep, Barbora Vander Wielen, Jonathan R Brestoff, Sheila A Stewart, David W Piston, Takeshi Egawa, Daniel Kreisel, Gwendalyn J Randolph, Maxim N Artyomov

2020-Current year OA Pubs

Aging strongly impacts CD8

Isg15 Negatively Regulates Ripk3-Mediated Cell Death And Viral Pathogenesis, Yi-Chieh Perng, Jessica M C Warsaw, Sachendra S Bais, Bradley E Hiller, Marissa C Locke, David J Morales-Heil, Chaoqun Li, Alissa R Young, Kristen J Monte, Robert E Schmidt, Douglas R Green, Yi-Nan Gong, Deborah J Lenschow

2020-Current year OA Pubs

Necroptosis, a form of programmed, inflammatory necrosis, plays an important role in viral-host defense and inflammation. The receptor-interacting protein kinase 3 (RIPK3)/mixed lineage kinase domain-like pseudokinase (MLKL) pathway mediates necroptosis. Yet, the mechanisms that control necroptosis to limit immunopathology are poorly understood. Here, we report that interferon-stimulated gene 15 (ISG15) negatively regulates RIPK3-mediated cell death, including necroptosis, and limits immunopathology during chikungunya virus (CHIKV) infection. ISG15-deficient mice infected with CHIKV display increased levels of necroptosis, resulting in elevated proinflammatory cytokine and chemokine production, leading to increased lethality. This dysregulated host response is fully prevented when MLKL or RIPK3 is ablated …

Dual Orexin Receptor Antagonism With Lemborexant Enhances Microglial Clearance Of Β-Amyloid In Mice, Ashish Sharma, Emiko Segawa, Xiaoying Chen, Sohui Park, Shoutang Wang, Riley E Irmen, Nicholas J Constantino, Chanung Wang, Michael F Kanan, Marco Colonna, Shannon L Macauley, Jocelyn Y Cheng, Ken Hatanaka, Margaret Moline, Erik S Musiek

2020-Current year OA Pubs

BACKGROUND: Sleep disturbances elevate brain amyloid-beta (Aβ) levels and represent a modifiable risk factor for Alzheimer's disease (AD). The orexin/hypocretin system regulates sleep-wake behavior and has emerged as a therapeutic target in AD; however, the effects of FDA-approved dual orexin receptor antagonists (DORAs) on amyloid pathology remain unclear. We compared lemborexant, an FDA-approved DORA, to doxepin, an antihistaminergic sleep medication, on amyloid pathology and microglial responses in PSAPP mice.

METHODS: PSAPP mice received lemborexant (10 or 30 mg/kg/day), doxepin (35 mg/kg/day), or vehicle for 6 weeks beginning prior to plaque onset or 4 weeks after established pathology. Sleep was assessed …

Target Ii Data Portal: A Multi-Omics Resource For Environmental Toxicant Studies In Mice, Prashant K Kuntala, Benpeng Miao, Deepak Purushotham, Bo Zhang, Daofeng Li, Ting Wang

2020-Current year OA Pubs

The Toxicant Exposures and Responses by Genomic and Epigenomic Regulators of Transcription (TaRGET) program is a multiphase program that aims to understand how environmental factors contribute to disease susceptibility using toxicant-exposed mouse models. Here, we present the TaRGET II Data Portal ( https://data.targetepigenomics.org/ ), a comprehensive repository of multi-omics datasets generated from mice exposed to a range of environmental toxicants, including arsenic (As), lead (Pb), bisphenol A (BPA), tributyltin (TBT), di(2-ethylhexyl) phthalate (DEHP), tetrachlorodibenzo-p-dioxin (TCDD), and ambient air pollution (PM2.5). Epigenomic profiling assays capturing alterations in chromatin accessibility, DNA methylation, gene expression, and histone modifications were produced across multiple research …

Decoding Spatial Transcriptomics Across Multicellular And Subcellular Resolutions, Chongyue Zhao, Hanqiu Zhao, Zhiyu Dai, Et Al.

2020-Current year OA Pubs

Current whole-genome spatial transcriptomics (ST) platforms, which range from multicellular (e.g., Visium) to subcellular resolution (e.g., Visium HD, Stereo-seq), face significant challenges in accurately decomposing or aggregating spots into single cells-the fundamental units of biological activity. To date, most existing computational methods operate at the spot level, and no method has effectively reconstructed transcriptomes at single-cell resolution. In this study, we present STARS (Spatial Transcriptomics across Resolutions for Single Cells). Leveraging Vision Transformer model and contrastive learning, STARS combines high-resolution histology images with spot-level transcriptomics data to reconstruct single-cell-level gene expression from multicellular and subcellular platforms. We demonstrate the advantage …

Harnessing Mechanobiology Of Resident Stem Cells To Refine Cell Based Therapeutics, Dakota R. Kamm

WUSM Theses and Dissertations – All Programs

Mesenchymal stem cells (MSCs) are resident cells residing with many adult tissues such as adipose tissue and bone marrow that have the potency for multiple lineage differentiation as well as the capacity to secrete a litany of beneficial factors to maintain homeostasis and promote tissue repair. Since 1995, MSCs have been used therapeutically to treat a variety of conditions from osteoarthritis to heart disease to muscle pathologies. Great leaps have been made in improving MSC-based therapies through optimization of culture methods and select enrichment of cellular subpopulations. More recently, the physical microenvironment of tissue in vivo and culture conditions in …

Longitudinal Changes In Cognition And Brain Imaging In Persons With Human Immunodeficiency Virus, James Kennedy, Sarah A Cooley, June Roman Fox, Kalen J Petersen, Elizabeth Westerhaus, Pat Reid, Linet Lopez, Beau M Ances

2020-Current year OA Pubs

BACKGROUND: As persons with human immunodeficiency virus (PWH) live longer, interactions between human immunodeficiency virus (HIV), aging, and structural brain integrity become increasingly vital for understanding cognitive disorders. This study analyzed the effects of aging, HIV serostatus, and viral load on cognition and brain volumes in a large cohort of persons without HIV (PWOH), PWH with undetectable virus (PWHU) (HIV RNA ≤50 copies/mL), and PWH with detectable virus (PHWD) (HIV RNA >50 copies/mL). Cross-sectional and longitudinal data were included.

METHODS: Cognitive composites (NPZ4) and brain volumes were obtained from 259 PWOH, 264 PWHU, and 84 PWHD with a total of …

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 …

Simultaneous Multielectrode Recordings Along The Human Scala Tympani: Evidence For Level-Dependent Place Coding, Amit Walia, Matthew A Shew, Shannon M Lefler, Amanda J Ortmann, Patrick Ioerger, Jordan Varghese, Jacques A Herzog, Craig A Buchman

2020-Current year OA Pubs

The cochlea systematically encodes sound frequency and intensity via a precisely organized tonotopic map, in which traveling waves peak at specific cochlear locations. A fundamental but incompletely understood aspect of auditory coding involves how stimulus intensity shapes this tonotopic organization. In animal models, increasing intensity shifts the cochlear traveling wave peak basally; however, physiological evidence for such intensity-dependent shifts in human cochlear processing is limited. Here, we performed simultaneous multielectrode electrocochleography recordings along the human scala tympani to characterize how cochlear place coding varies as a function of stimulus intensity. In subjects with preserved cochlear mechanics, including individuals with auditory …

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

Inflammatory Markers In The Emergency Department And Ptsd Symptoms In The Aurora Study: A Longitudinal Cohort Study, Kristen Nishimi, Stacey L House, Et Al.

2020-Current year OA Pubs

BACKGROUND: Systemic inflammation is hypothesized to contribute to post-traumatic stress disorder (PTSD) vulnerability. Few studies have examined inflammation shortly after trauma as a predictor of later PTSD symptoms. We examined whether inflammation from the emergency department (ED) post-trauma is associated with PTSD symptom severity over the following 6 months.

METHODS: Our sample included 742 AURORA participants, a longitudinal cohort of patients in 29 EDs across the United States after a traumatic stressor, followed up to 6 months. Plasma cytokines were assessed from a study blood draw in the ED: an inflammatory index (standardized sum of generally pro-inflammatory markers interleukin [IL]-6, …

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 …

+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

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 …

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 …

A Covalent Allosteric Molecular Glue Suppresses Nrf2-Dependent Cancer Growth, Nilotpal Roy, Ilah Bok, Harit Panda, Dhaval P Bhatt, Emily M Wilkerson, Soma Saeidi, Paul Zolkind, Michael B Major, Et Al.

2020-Current year OA Pubs

UNLABELLED: The NRF2 transcription factor is constitutively active in cancer, in which it functions to maintain oxidative homeostasis and reprogram cellular metabolism. NRF2-active tumors exhibit NRF2 dependency and resistance to chemotherapy/radiotherapy (RT). In this study, we characterize VVD-065, a first-in-class NRF2 inhibitor that acts via an unprecedented allosteric molecular glue mechanism. In the absence of stress or mutation, NRF2 is rapidly degraded by the Kelch-like ECH-associated protein 1 (KEAP1)-cullin3 (CUL3) ubiquitin-ligase complex. VVD-065 specifically and covalently engages Cys151 on KEAP1, which in turn promotes KEAP1-CUL3 complex formation, leading to enhancement of NRF2 degradation. Previously reported Cys151-directed compounds decrease KEAP1-CUL3 interactions …

Computational Fluid Dynamics-Based Risk Stratification Of Modified Blalock-Taussig-Thomas Shunt Thrombogenicity, Yi Qiao, Ethan Penn, Jacob Miller, Scott Bugenhagen, Ram Rohatgi, Kelsey Mercer, Blaire Kulp, Jinli Wang, Pirooz Eghtesady, Guy M Genin, Edon J Rabinowitz, David Bark

2020-Current year OA Pubs

BACKGROUND: The modified Blalock-Taussig-Thomas shunt (mBTTS) is a critical palliative procedure for infants with single-ventricle physiology, but thrombosis-related occlusion affects 8% to 12% of infants and carries nearly 50% mortality. Meanwhile, existing antithrombotic strategies fail to address the hemodynamic factors driving thrombosis, highlighting the need for a deeper understanding of flow dynamics in shunt failure.

OBJECTIVES: This study aims to identify how mBTTS geometry influences hemodynamics and thrombosis risk, providing quantitative guidance for surgical planning and shunt design optimization.

METHODS: We used patient-specific imaging data to test 54 idealized mBTTS configurations, systematically varying key geometric factors: pulmonary artery diameter, shunt …

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

Adaptive Evolution Of Gene Regulatory Networks In Mammalian Neocortex, Zhuo Li, Linda J Richards, Et Al.

2020-Current year OA Pubs

Mammals have evolved a more complex brain, exemplified by the transformation of the single-layer dorsal cortex of excitatory projection neurons (ExNs) in ancestors into a multilayered cerebral neocortex

Synovial Fluid Biomarkers Associated With Anterior Cruciate Ligament Injury And Reconstruction: A Systematic Review, Daniel C Touhey, Derrick M Knapik, Sina Tartibi, Varun Gopinatth, Tanya Boghosian, Matthew J Matava, Matthew V Smith, Robert H Brophy

2020-Current year OA Pubs

BACKGROUND: Synovial fluid biomarkers reflect the inflammatory response after joint injury and surgery. Previous studies have identified synovial fluid biomarker concentrations in the knee after both anterior cruciate ligament (ACL) injury and ACL reconstruction (ACLR).

PURPOSE: To systematically review the literature to summarize reported changes in synovial fluid biomarkers and their concentrations after acute ACL injury/ACLR.

STUDY DESIGN: Systematic review; Level of evidence, 4.

METHODS: Studies published in the PubMed, EMBASE, and the Cochrane Library databases reporting in English on humans sustaining ACL tears and undergoing ACLR from inception to August 2025 were identified and included if postinjury/preoperative and/or postoperative …

Preterm Birth Increases Susceptibility To Hyperglycemia-Induced Kidney Injury With Sex-Specific Differences In Structural And Molecular Responses, Rachel K Dailey, Aleksandra Cwiek, Logan C Hamil, Sage Timberline, Ayyappa Kumar Sista Kameshwar, Masako Suzuki, Jaya Isaac, Kimberly Deronde, Mark Conaway, Kevin M Bennett, Edwin J Baldelomar, Matthew R Hoch, Kimberly J Reidy, Jennifer R Charlton

2020-Current year OA Pubs

BACKGROUND: Preterm birth increases the long-term risk of diabetes and chronic kidney disease (CKD), yet its impact on diabetic kidney disease (DKD) is unclear. We previously showed that male preterm mice with diabetes develop early features of DKD, including reduced podocyte density, decreased renin expression, activation of angiogenesis pathways, and impaired endothelial-podocyte signaling. Here, we examine whether preterm birth similarly accelerates DKD progression in female mice and compare structural and transcriptomic outcomes in the females to the prior male cohort to assess sex-specific differences.

METHODS: Preterm mice were delivered by Caesarean section at 19 days post conception (dpc) and term …

Primary Cilia Regulate Glp-1 Signaling In Pancreatic Β Cells, Isabella Melena, Jeong Hun Jo, Shannon E Townsend, Samantha Adamson Digruccio, Xinhang Dong, Lifei Zhu, Jonathan Campbell, Jing W Hughes

2020-Current year OA Pubs

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are mainstay therapies for diabetes and obesity, acting in part by enhancing glucose-dependent insulin secretion. While the primary cilium is a known signaling compartment for certain G-protein coupled receptors (GPCRs), its role in the β-cell response to incretins remains undefined. Here, we show that primary cilia are essential for full GLP-1R signaling. Loss of β-cell cilia in mouse and human islets severely impaired GLP-1-potentiated insulin secretion, an effect preceded by blunted whole-cell cAMP and Ca

B Cell Expression Of An Enzymatic Intermediary In Ether Lipid Biosynthesis Promotes Antibody Responses And Germinal Center Size, Sung Hoon Cho, Marissa A Jones, Kaylor Meyer, David M Anderson, Sergiy Chetyrkin, M Wade Calcutt, Richard M Caprioli, Clay F Semenkovich, Mark R Boothby

2020-Current year OA Pubs

The qualities of antibody (Ab) responses provided by B lymphocytes and their plasma cell (PC) descendants are crucial facets of responses to vaccines and microbes. Metabolic processes and products regulate aspects of B cell proliferation and differentiation into germinal center (GC) and PC states along with Ab diversification. However, there is little information about lymphoid-cell-intrinsic functions of enzymes that mediate ether lipid biosynthesis. Imaging mass spectrometry (IMS) results had indicated that concentrations of a number of these phospholipids were substantially enhanced in GC compared to the background average in spleens, but it was unclear if biosynthesis in B cells was …