Life Sciences Commons^™

Differentiation Of Fetal Hematopoietic Stem Cells Requires Arid4b To Restrict Autocrine Kitlg/Kit-Src Signaling., In-Chi Young, Bogang Wu, Jaclyn Andricovich, Sung-Ting Chuang, Rong Li, Alexandros Tzatsos, Ray-Chang Wu, Mei-Yi Wu

Anatomy and Regenerative Biology Faculty Publications

No abstract provided.

Corneal Nonmyelinating Schwann Cells Illuminated By Single-Cell Transcriptomics And Visualized By Protein Biomarkers., Paola Bargagna-Mohan, Gwendolyn Schultz, Bruce Rheaume, Ephraim F Trakhtenberg, Paul Robson, Sonali Pal-Ghosh, Mary Ann Stepp, Katherine S Given, Wendy B Macklin, Royce Mohan

Anatomy and Regenerative Biology Faculty Publications

No abstract provided.

Constitutive Activation Of Kappa Opioid Receptors At Ventral Tegmental Area Inhibitory Synapses Following Acute Stress., Abigail M Polter, Kelsey Barcomb, Rudy W Chen, Paige M Dingess, Nicholas M Graziane, Travis E Brown, Julie A Kauer

Pharmacology and Physiology Faculty Publications

Stressful experiences potently activate kappa opioid receptors (κORs). κORs in the ventral tegmental area regulate multiple aspects of dopaminergic and non-dopaminergic cell function. Here we show that at GABAergic synapses on rat VTA dopamine neurons, a single exposure to a brief cold-water swim stress induces prolonged activation of κORs. This is mediated by activation of the receptor during the stressor followed by a persistent, ligand-independent constitutive activation of the κOR itself. This lasting change in function is not seen at κORs at neighboring excitatory synapses, suggesting distinct time courses and mechanisms of regulation of different subsets of κORs. We also …

Development Of Activity In The Mouse Visual Cortex., Jing Shen, Matthew T Colonnese

Pharmacology and Physiology Faculty Publications

No abstract provided.

Genetic Modification Of Human Mesenchymal Stem Cells Helps To Reduce Adiposity And Improve Glucose Tolerance In An Obese Diabetic Mouse Model., Sabyasachi Sen, Cleyton C Domingues, Carol Rouphael, Cyril Chou, Chul Kim, Nagendra Yadava

Medicine Faculty Publications

INTRODUCTION: Human mesenchymal stem cells (MSCs) are multipotent cells that can differentiate into fat, muscle, bone and cartilage cells. Exposure of subcutaneous abdominal adipose tissue derived AD-MSCs to high glucose (HG) leads to superoxide accumulation and up-regulation of inflammatory molecules. Our aim was to inquire how HG exposure affects MSCs differentiation and whether the mechanism is reversible.

METHODS: We exposed human adipose tissue derived MSCs to HG (25 mM) and compared it to normal glucose (NG, 5.5 mM) exposed cells at 7, 10 and 14 days. We examined mitochondrial superoxide accumulation (Mitosox-Red), cellular oxygen consumption rate (OCR, Seahorse) and gene …

Pharmaceutical Integrated Stress Response Enhancement Protects Oligodendrocytes And Provides A Potential Multiple Sclerosis Therapeutic., Sharon W Way, Joseph R Podojil, Benjamin L Clayton, Anita Zaremba, Tassie L Collins, Rejani B Kunjamma, Andrew P Robinson, Pedro Brugarolas, Robert H. Miller, Stephen D Miller, Brian Popko

Anatomy and Regenerative Biology Faculty Publications

Oligodendrocyte death contributes to the pathogenesis of the inflammatory demyelinating disease multiple sclerosis (MS). Nevertheless, current MS therapies are mainly immunomodulatory and have demonstrated limited ability to inhibit MS progression. Protection of oligodendrocytes is therefore a desirable strategy for alleviating disease. Here we demonstrate that enhancement of the integrated stress response using the FDA-approved drug guanabenz increases oligodendrocyte survival in culture and prevents hypomyelination in cerebellar explants in the presence of interferon-γ, a pro-inflammatory cytokine implicated in MS pathogenesis. In vivo, guanabenz treatment protects against oligodendrocyte loss caused by CNS-specific expression of interferon-γ. In a mouse model of MS, experimental …

Atrial Fibrillation: Biophysics, Molecular Mechanisms, And Novel Therapies., Alexey V. Glukhov, Leonid V. Rosenshtraukh, Anamika Bhargava, Michele Miragoli, Bas J. D. Boukens

Anatomy and Regenerative Biology Faculty Publications

No abstract provided.

Transcriptional Pathways Associated With Skeletal Muscle Changes After Spinal Cord Injury And Treadmill Locomotor Training., Celine Baligand, Yi-Wen Chen, Fan Ye, Sachchida Nand Pandey, San-Huei Lai, Min Liu, Krista Vandenborne

Genomics and Precision Medicine Faculty Publications

The genetic and molecular events associated with changes in muscle mass and function after SCI and after the implementation of candidate therapeutic approaches are still not completely known. The overall objective of this study was to identify key molecular pathways activated with muscle remodeling after SCI and locomotor training. We implemented treadmill training in a well-characterized rat model of moderate SCI and performed genome wide expression profiling on soleus muscles at multiple time points: 3, 8, and 14 days after SCI. We found that the activity of the protein ubiquitination and mitochondrial function related pathways was altered with SCI and …

Cc2d1a Regulates Human Intellectual And Social Function As Well As Nf-Κb Signaling Homeostasis., M. Chiara Manzini, Lan Xiong, Ranad Shaheen, Dimira E Tambunan, Stefania Di Costanzo, Vanessa Mitisalis, +15 Additional Authors

Pharmacology and Physiology Faculty Publications

Autism spectrum disorder (ASD) and intellectual disability (ID) are often comorbid, but the extent to which they share common genetic causes remains controversial. Here, we present two autosomal-recessive "founder" mutations in the CC2D1A gene causing fully penetrant cognitive phenotypes, including mild-to-severe ID, ASD, as well as seizures, suggesting shared developmental mechanisms. CC2D1A regulates multiple intracellular signaling pathways, and we found its strongest effect to be on the transcription factor nuclear factor κB (NF-κB). Cc2d1a gain and loss of function both increase activation of NF-κB, revealing a critical role of Cc2d1a in homeostatic control of intracellular signaling. Cc2d1a knockdown in neurons …