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Articles 1501 - 1530 of 8115
Full-Text Articles in Entire DC Network
Predicting Alcohol-Related Memory Problems In Older Adults: A Machine Learning Study With Multi-Domain Features, Chella Kamarajan, Andrey P Anokhin, Sarah Hartz, Laura J Bierut, Vivia V Mccutcheon, Kathleen K Bucholz, Et Al.
Predicting Alcohol-Related Memory Problems In Older Adults: A Machine Learning Study With Multi-Domain Features, Chella Kamarajan, Andrey P Anokhin, Sarah Hartz, Laura J Bierut, Vivia V Mccutcheon, Kathleen K Bucholz, Et Al.
2020-Current year OA Pubs
Memory problems are common among older adults with a history of alcohol use disorder (AUD). Employing a machine learning framework, the current study investigates the use of multi-domain features to classify individuals with and without alcohol-induced memory problems. A group of 94 individuals (ages 50-81 years) with alcohol-induced memory problems (the memory group) were compared with a matched control group who did not have memory problems. The random forests model identified specific features from each domain that contributed to the classification of the memory group vs. the control group (AUC = 88.29%). Specifically, individuals from the memory group manifested a …
Circadian Clock Protein Bmal1 Broadly Influences Autophagy And Endolysosomal Function In Astrocytes, Celia A Mckee, Alexander J Polino, Melvin W King, Erik S Musiek
Circadian Clock Protein Bmal1 Broadly Influences Autophagy And Endolysosomal Function In Astrocytes, Celia A Mckee, Alexander J Polino, Melvin W King, Erik S Musiek
2020-Current year OA Pubs
An emerging role for the circadian clock in autophagy and lysosome function has opened new avenues for exploration in the field of neurodegeneration. The daily rhythms of circadian clock proteins may coordinate gene expression programs involved not only in daily rhythms but in many cellular processes. In the brain, astrocytes are critical for sensing and responding to extracellular cues to support neurons. The core clock protein BMAL1 serves as the primary positive circadian transcriptional regulator and its depletion in astrocytes not only disrupts circadian function but also leads to a unique cell-autonomous activation phenotype. We report here that astrocyte-specific deletion …
Developing Tools For The Implementation And Evaluation Of Participatory Worker Health Promotion Interventions, Ryan J. Walsh
Developing Tools For The Implementation And Evaluation Of Participatory Worker Health Promotion Interventions, Ryan J. Walsh
WUSM Theses and Dissertations – All Programs
The chronic disease burden among American workers leads to substantial expenditures on healthcare, lost productivity at work, and reduced quality of life. Workers from communities of lower socioeconomic status (SES) shoulder a disproportionate burden of chronic diseases and costs. A promising strategy for addressing this population health burden is to develop and implement participatory worker health promotion interventions in workplaces. Part of this effort to develop and implement these programs entails improving the quality of evaluation tools and approaches. Thus, we completed a series of secondary analyses of a large participatory worker health promotion program trial called Working For You. …
Effect Of Obesity And Insulin Resistance On Glucose And Fatty Acid Metabolism, Chao Cao
Effect Of Obesity And Insulin Resistance On Glucose And Fatty Acid Metabolism, Chao Cao
WUSM Theses and Dissertations – All Programs
In people with obesity, insulin resistance of glucose and fatty acid metabolism is common and it is thought that insulin resistance of fatty acid metabolism is involved in causing insulin resistance of glucose metabolism and subsequently hyperglycemia through a mechanism referred to as “lipotoxicity”. However, in many individuals with obesity and insulin resistance fasting plasma glucose and free fatty acid (FFA) concentrations are not elevated. It is widely believed that pancreatic beta-cells detect the need to increase insulin secretion in order to compensate for the impaired insulin action caused by insulin resistance in these people, whereas beta-cell dysfunction results in …
Biomechanical Models And Mechanisms Of Cellular Morphogenesis And Cerebral Cortical Expansion And Folding, David C Van Essen
Biomechanical Models And Mechanisms Of Cellular Morphogenesis And Cerebral Cortical Expansion And Folding, David C Van Essen
2020-Current year OA Pubs
Morphogenesis of the nervous system involves a highly complex spatio-temporal pattern of physical forces (mainly tension and pressure) acting on cells and tissues that are pliable but have an intricately organized cytoskeletal infrastructure. This review begins by covering basic principles of biomechanics and the core cytoskeletal toolkit used to regulate the shapes of cells and tissues during embryogenesis and neural development. It illustrates how the principle of 'tensegrity' provides a useful conceptual framework for understanding how cells dynamically respond to forces that are generated internally or applied externally. The latter part of the review builds on this foundation in considering …
Modulating Fast Skeletal Muscle Contraction Protects Skeletal Muscle In Animal Models Of Duchenne Muscular Dystrophy, Alan J. Russell, Twlya I. Juehne, Jinsheng Yu, Et Al.
Modulating Fast Skeletal Muscle Contraction Protects Skeletal Muscle In Animal Models Of Duchenne Muscular Dystrophy, Alan J. Russell, Twlya I. Juehne, Jinsheng Yu, Et Al.
2020-Current year OA Pubs
Duchenne muscular dystrophy (DMD) is a lethal muscle disease caused by absence of the protein dystrophin, which acts as a structural link between the basal lamina and contractile machinery to stabilize muscle membranes in response to mechanical stress. In DMD, mechanical stress leads to exaggerated membrane injury and fiber breakdown, with fast fibers being the most susceptible to damage. A major contributor to this injury is muscle contraction, controlled by the motor protein myosin. However, how muscle contraction and fast muscle fiber damage contribute to the pathophysiology of DMD has not been well characterized. We explored the role of fast …
Single-Nucleus Multi-Omics Of Human Stem Cell-Derived Islets Identifies Deficiencies In Lineage Specification, Punn Augsornworawat, Nathaniel J Hogrebe, Matthew Ishahak, Mason D Schmidt, Erica Marquez, Marlie M Maestas, Daniel A Veronese-Paniagua, Sarah E Gale, Julia R Miller, Leonardo Velazco-Cruz, Jeffrey R Millman
Single-Nucleus Multi-Omics Of Human Stem Cell-Derived Islets Identifies Deficiencies In Lineage Specification, Punn Augsornworawat, Nathaniel J Hogrebe, Matthew Ishahak, Mason D Schmidt, Erica Marquez, Marlie M Maestas, Daniel A Veronese-Paniagua, Sarah E Gale, Julia R Miller, Leonardo Velazco-Cruz, Jeffrey R Millman
2020-Current year OA Pubs
Insulin-producing β cells created from human pluripotent stem cells have potential as a therapy for insulin-dependent diabetes, but human pluripotent stem cell-derived islets (SC-islets) still differ from their in vivo counterparts. To better understand the state of cell types within SC-islets and identify lineage specification deficiencies, we used single-nucleus multi-omic sequencing to analyse chromatin accessibility and transcriptional profiles of SC-islets and primary human islets. Here we provide an analysis that enabled the derivation of gene lists and activity for identifying each SC-islet cell type compared with primary islets. Within SC-islets, we found that the difference between β cells and awry …
Trem2 Inhibition Triggers Antitumor Cell Activity Of Myeloid Cells In Glioblastoma, Rui Sun, Rowland Han, Colin Mccornack, Saad Khan, G Travis Tabor, Yun Chen, Jinchao Hou, Haowu Jiang, Kathleen M Schoch, Diane D Mao, Ryan Cleary, Alicia Yang, Qin Liu, Jingqin Luo, Allegra Petti, Timothy M Miller, Jason D Ulrich, David M Holtzman, Albert H Kim
Trem2 Inhibition Triggers Antitumor Cell Activity Of Myeloid Cells In Glioblastoma, Rui Sun, Rowland Han, Colin Mccornack, Saad Khan, G Travis Tabor, Yun Chen, Jinchao Hou, Haowu Jiang, Kathleen M Schoch, Diane D Mao, Ryan Cleary, Alicia Yang, Qin Liu, Jingqin Luo, Allegra Petti, Timothy M Miller, Jason D Ulrich, David M Holtzman, Albert H Kim
2020-Current year OA Pubs
Triggering receptor expressed on myeloid cells 2 (TREM2) plays important roles in brain microglial function in neurodegenerative diseases, but the role of TREM2 in the GBM TME has not been examined. Here, we found that TREM2 is highly expressed in myeloid subsets, including macrophages and microglia in human and mouse GBM tumors and that high TREM2 expression correlates with poor prognosis in patients with GBM. TREM2 loss of function in human macrophages and mouse myeloid cells increased interferon-γ-induced immunoactivation, proinflammatory polarization, and tumoricidal capacity. In orthotopic mouse GBM models, mice with chronic and acute Trem2 loss of function exhibited decreased …
Two Forms Of Asynchronous Release With Distinctive Spatiotemporal Dynamics In Central Synapses, Gerardo Malagon, Jongyun Myeong, Vitaly A Klyachko
Two Forms Of Asynchronous Release With Distinctive Spatiotemporal Dynamics In Central Synapses, Gerardo Malagon, Jongyun Myeong, Vitaly A Klyachko
2020-Current year OA Pubs
Asynchronous release is a ubiquitous form of neurotransmitter release that persists for tens to hundreds of milliseconds after an action potential. How asynchronous release is organized and regulated at the synaptic active zone (AZ) remains debatable. Using nanoscale-precision imaging of individual release events in rat hippocampal synapses, we observed two spatially distinct subpopulations of asynchronous events, ~75% of which occurred inside the AZ and with a bias towards the AZ center, while ~25% occurred outside of the functionally defined AZ, that is, ectopically. The two asynchronous event subpopulations also differed from each other in temporal properties, with ectopic events occurring …
Co-Clinical Imaging Metadata Information (Cimi) For Cancer Research To Promote Open Science, Standardization, And Reproducibility In Preclinical Imaging, Stephen M Moore, James D Quirk, Andrew W Lassiter, Richard Laforest, Kooresh I Shoghi, Et Al.
Co-Clinical Imaging Metadata Information (Cimi) For Cancer Research To Promote Open Science, Standardization, And Reproducibility In Preclinical Imaging, Stephen M Moore, James D Quirk, Andrew W Lassiter, Richard Laforest, Kooresh I Shoghi, Et Al.
2020-Current year OA Pubs
Preclinical imaging is a critical component in translational research with significant complexities in workflow and site differences in deployment. Importantly, the National Cancer Institute's (NCI) precision medicine initiative emphasizes the use of translational co-clinical oncology models to address the biological and molecular bases of cancer prevention and treatment. The use of oncology models, such as patient-derived tumor xenografts (PDX) and genetically engineered mouse models (GEMMs), has ushered in an era of co-clinical trials by which preclinical studies can inform clinical trials and protocols, thus bridging the translational divide in cancer research. Similarly, preclinical imaging fills a translational gap as an …
Rbm47 Regulates Intestinal Injury And Tumorigenesis By Modifying Proliferation, Oxidative Response, And Inflammatory Pathways, Saeed Soleymanjahi, Valerie Blanc, Elizabeth A. Molitor, David M. Alvarado, Yan Xie, Vered Gazit, Jeffrey W. Brown, Kathleen Byrnes, Ta-Chiang Liu, Jason C. Mills, Matthew A. Ciorba, Deborah C. Rubin, Nicholas O. Davidson
Rbm47 Regulates Intestinal Injury And Tumorigenesis By Modifying Proliferation, Oxidative Response, And Inflammatory Pathways, Saeed Soleymanjahi, Valerie Blanc, Elizabeth A. Molitor, David M. Alvarado, Yan Xie, Vered Gazit, Jeffrey W. Brown, Kathleen Byrnes, Ta-Chiang Liu, Jason C. Mills, Matthew A. Ciorba, Deborah C. Rubin, Nicholas O. Davidson
2020-Current year OA Pubs
RNA-binding protein 47 (RBM47) is required for embryonic endoderm development, but a role in adult intestine is unknown. We studied intestine-specific Rbm47-knockout mice (Rbm47-IKO) following intestinal injury and made crosses into ApcMin/+ mice to examine alterations in intestinal proliferation, response to injury, and tumorigenesis. We also interrogated human colorectal polyps and colon carcinoma tissue. Rbm47-IKO mice exhibited increased proliferation and abnormal villus morphology and cellularity, with corresponding changes in Rbm47-IKO organoids. Rbm47-IKO mice adapted to radiation injury and were protected against chemical-induced colitis, with Rbm47-IKO intestine showing upregulation of antioxidant and Wnt signaling pathways as well as stem cell and …
Polarized Localization Of Phosphatidylserine In The Endothelium Regulates Kir2.1, Claire A. Ruddiman, Richard Peckham, Melissa A. Luse, Yen-Lin Chen, Maniselvan Kuppusamy, Bruce A. Corliss, P. Jordan Hall, Chien-Jung Lin, Shayn M. Peirce, Swapnil K. Sonkusare, Robert P. Mecham, Jessica E. Wagenseil, Brant E. Isakson
Polarized Localization Of Phosphatidylserine In The Endothelium Regulates Kir2.1, Claire A. Ruddiman, Richard Peckham, Melissa A. Luse, Yen-Lin Chen, Maniselvan Kuppusamy, Bruce A. Corliss, P. Jordan Hall, Chien-Jung Lin, Shayn M. Peirce, Swapnil K. Sonkusare, Robert P. Mecham, Jessica E. Wagenseil, Brant E. Isakson
2020-Current year OA Pubs
Lipid regulation of ion channels is largely explored using in silico modeling with minimal experimentation in intact tissue; thus, the functional consequences of these predicted lipid-channel interactions within native cellular environments remain elusive. The goal of this study is to investigate how lipid regulation of endothelial Kir2.1 - an inwardly rectifying potassium channel that regulates membrane hyperpolarization - contributes to vasodilation in resistance arteries. First, we show that phosphatidylserine (PS) localizes to a specific subpopulation of myoendothelial junctions (MEJs), crucial signaling microdomains that regulate vasodilation in resistance arteries, and in silico data have implied that PS may compete with phosphatidylinositol …
Infection Of Neonatal Mice With The Murine Norovirus Strain Wu23 Is A Robust Model To Study Norovirus Pathogenesis, Amy M Peiper, Emily W Helm, Quyen Nguyen, Matthew Phillips, Caroline G Williams, Dhairya Shah, Sarah Tatum, Neha Iyer, Marco Grodzki, Laura B Eurell, Aqsa Nasir, Megan T Baldridge, Stephanie M Karst
Infection Of Neonatal Mice With The Murine Norovirus Strain Wu23 Is A Robust Model To Study Norovirus Pathogenesis, Amy M Peiper, Emily W Helm, Quyen Nguyen, Matthew Phillips, Caroline G Williams, Dhairya Shah, Sarah Tatum, Neha Iyer, Marco Grodzki, Laura B Eurell, Aqsa Nasir, Megan T Baldridge, Stephanie M Karst
2020-Current year OA Pubs
Noroviruses are the leading cause of severe childhood diarrhea and foodborne disease worldwide. While they are a major cause of disease in all age groups, infections in the very young can be quite severe, with annual estimates of 50,000-200,000 fatalities in children under 5 years old. In spite of the remarkable disease burden associated with norovirus infections, very little is known about the pathogenic mechanisms underlying norovirus diarrhea, principally because of the lack of tractable small animal models. The development of the murine norovirus (MNV) model nearly two decades ago has facilitated progress in understanding host-norovirus interactions and norovirus strain …
State-Level Macro-Economic Factors Moderate The Association Of Low Income With Brain Structure And Mental Health In U.S. Children, David G Weissman, Mark L Hatzenbuehler, Mina Cikara, Deanna M Barch, Katie A Mclaughlin
State-Level Macro-Economic Factors Moderate The Association Of Low Income With Brain Structure And Mental Health In U.S. Children, David G Weissman, Mark L Hatzenbuehler, Mina Cikara, Deanna M Barch, Katie A Mclaughlin
2020-Current year OA Pubs
Macrostructural characteristics, such as cost of living and state-level anti-poverty programs relate to the magnitude of socioeconomic disparities in brain development and mental health. In this study we leveraged data from the Adolescent Brain and Cognitive Development (ABCD) study from 10,633 9-11 year old youth (5115 female) across 17 states. Lower income was associated with smaller hippocampal volume and higher internalizing psychopathology. These associations were stronger in states with higher cost of living. However, in high cost of living states that provide more generous cash benefits for low-income families, socioeconomic disparities in hippocampal volume were reduced by 34%, such that …
Whole-Exome Sequencing Prioritizes Candidate Genes For Hereditary Cataract In The Emory Mouse Mutant, Thomas M Bennett, Yuefang Zhou, Kacie J Meyer, Michael G Anderson, Alan Shiels
Whole-Exome Sequencing Prioritizes Candidate Genes For Hereditary Cataract In The Emory Mouse Mutant, Thomas M Bennett, Yuefang Zhou, Kacie J Meyer, Michael G Anderson, Alan Shiels
2020-Current year OA Pubs
The Emory cataract (Em) mouse mutant has long been proposed as an animal model for age-related or senile cataract in humans-a leading cause of visual impairment. However, the genetic defect(s) underlying the autosomal dominant Em phenotype remains elusive. Here, we confirmed development of the cataract phenotype in commercially available Em/J mice [but not ancestral Carworth Farms White (CFW) mice] at 6-8 months of age and undertook whole-exome sequencing of candidate genes for Em. Analysis of coding and splice-site variants did not identify any disease-causing/associated mutations in over 450 genes known to underlie inherited and age-related forms of cataract and other …
Katp Channels Are Necessary For Glucose-Dependent Increases In Amyloid-Β And Alzheimer's Disease-Related Pathology, John Grizzanti, William R. Moritz, Molly Stanley, Emily E. Caesar, Maria S. Remedi, Celeste M. Karch, Colin G. Nichols, David M. Holtzman, Et Al.
Katp Channels Are Necessary For Glucose-Dependent Increases In Amyloid-Β And Alzheimer's Disease-Related Pathology, John Grizzanti, William R. Moritz, Molly Stanley, Emily E. Caesar, Maria S. Remedi, Celeste M. Karch, Colin G. Nichols, David M. Holtzman, Et Al.
2020-Current year OA Pubs
Elevated blood glucose levels, or hyperglycemia, can increase brain excitability and amyloid-β (Aβ) release, offering a mechanistic link between type 2 diabetes and Alzheimer's disease (AD). Since the cellular mechanisms governing this relationship are poorly understood, we explored whether ATP-sensitive potassium (KATP) channels, which couple changes in energy availability with cellular excitability, play a role in AD pathogenesis. First, we demonstrate that KATP channel subunits Kir6.2/KCNJ11 and SUR1/ABCC8 were expressed on excitatory and inhibitory neurons in the human brain, and cortical expression of KCNJ11 and ABCC8 changed with AD pathology in humans and mice. Next, we explored whether eliminating neuronal …
Immunotherapeutic Approach To Reduce Senescent Cells And Alleviate Senescence-Associated Secretory Phenotype In Mice, Niraj Shrestha, Mark Foster, Lynne Marsala, Pamela Wong, Celia C Cubitt, Jennifer A Foltz, Jennifer Tran, Timothy Schappe, Melissa M Berrien-Elliott, Todd A Fehniger, Et Al.
Immunotherapeutic Approach To Reduce Senescent Cells And Alleviate Senescence-Associated Secretory Phenotype In Mice, Niraj Shrestha, Mark Foster, Lynne Marsala, Pamela Wong, Celia C Cubitt, Jennifer A Foltz, Jennifer Tran, Timothy Schappe, Melissa M Berrien-Elliott, Todd A Fehniger, Et Al.
2020-Current year OA Pubs
Accumulation of senescent cells (SNCs) with a senescence-associated secretory phenotype (SASP) has been implicated as a major source of chronic sterile inflammation leading to many age-related pathologies. Herein, we provide evidence that a bifunctional immunotherapeutic, HCW9218, with capabilities of neutralizing TGF-β and stimulating immune cells, can be safely administered systemically to reduce SNCs and alleviate SASP in mice. In the diabetic db/db mouse model, subcutaneous administration of HCW9218 reduced senescent islet β cells and SASP resulting in improved glucose tolerance, insulin resistance, and aging index. In naturally aged mice, subcutaneous administration of HCW9218 durably reduced the level of SNCs and …
Distinct Effects Of Two Hearing Loss-Associated Mutations In The Sarcomeric Myosin Myh7b, Lindsey A Lee, Samantha K Barrick, Ada E Buvoli, Jonathan Walklate, W Tom Stump, Michael Geeves, Michael J Greenberg, Leslie A Leinwand
Distinct Effects Of Two Hearing Loss-Associated Mutations In The Sarcomeric Myosin Myh7b, Lindsey A Lee, Samantha K Barrick, Ada E Buvoli, Jonathan Walklate, W Tom Stump, Michael Geeves, Michael J Greenberg, Leslie A Leinwand
2020-Current year OA Pubs
For decades, sarcomeric myosin heavy chain proteins were assumed to be restricted to striated muscle where they function as molecular motors that contract muscle. However, MYH7b, an evolutionarily ancient member of this myosin family, has been detected in mammalian nonmuscle tissues, and mutations in MYH7b are linked to hereditary hearing loss in compound heterozygous patients. These mutations are the first associated with hearing loss rather than a muscle pathology, and because there are no homologous mutations in other myosin isoforms, their functional effects were unknown. We generated recombinant human MYH7b harboring the D515N or R1651Q hearing loss-associated mutation and studied …
Steady-State Memory-Phenotype Conventional Cd4+ T Cells Exacerbate Autoimmune Neuroinflammation In A Bystander Manner Via The Bhlhe40/Gm-Csf Axis, Min-Ji Cho, Hong-Gyun Lee, Jae-Won Yoon, Gil-Ran Kim, Ja-Hyun Koo, Reshma Taneja, Brian T Edelson, You Jeong Lee, Je-Min Choi
Steady-State Memory-Phenotype Conventional Cd4+ T Cells Exacerbate Autoimmune Neuroinflammation In A Bystander Manner Via The Bhlhe40/Gm-Csf Axis, Min-Ji Cho, Hong-Gyun Lee, Jae-Won Yoon, Gil-Ran Kim, Ja-Hyun Koo, Reshma Taneja, Brian T Edelson, You Jeong Lee, Je-Min Choi
2020-Current year OA Pubs
Memory-phenotype (MP) CD4
Differential Regulation Of Cardiac Sodium Channels By Intracellular Fibroblast Growth Factors, Paweorn Angsutararux, Amal K Dutta, Martina Marras, Carlota Abella, Rebecca L Mellor, Jingyi Shi, Jeanne M Nerbonne, Jonathan R Silva
Differential Regulation Of Cardiac Sodium Channels By Intracellular Fibroblast Growth Factors, Paweorn Angsutararux, Amal K Dutta, Martina Marras, Carlota Abella, Rebecca L Mellor, Jingyi Shi, Jeanne M Nerbonne, Jonathan R Silva
2020-Current year OA Pubs
Voltage-gated sodium (NaV) channels are responsible for the initiation and propagation of action potentials. In the heart, the predominant NaV1.5 α subunit is composed of four homologous repeats (I-IV) and forms a macromolecular complex with multiple accessory proteins, including intracellular fibroblast growth factors (iFGF). In spite of high homology, each of the iFGFs, iFGF11-iFGF14, as well as the individual iFGF splice variants, differentially regulates NaV channel gating, and the mechanisms underlying these differential effects remain elusive. Much of the work exploring iFGF regulation of NaV1.5 has been performed in mouse and rat ventricular myocytes in which iFGF13VY is the predominant …
Bk Channels Of Five Different Subunit Combinations Underlie The De Novo Kcnma1 G375r Channelopathy, Yanyan Geng, Ping Li, Alice Butler, Bill Wang, Lawrence Salkoff, Karl L Magleby
Bk Channels Of Five Different Subunit Combinations Underlie The De Novo Kcnma1 G375r Channelopathy, Yanyan Geng, Ping Li, Alice Butler, Bill Wang, Lawrence Salkoff, Karl L Magleby
2020-Current year OA Pubs
The molecular basis of a severe developmental and neurological disorder associated with a de novo G375R variant of the tetrameric BK channel is unknown. Here, we address this question by recording from single BK channels expressed to mimic a G375R mutation heterozygous with a WT allele. Five different types of functional BK channels were expressed: 3% were consistent with WT, 12% with homotetrameric mutant, and 85% with three different types of hybrid (heterotetrameric) channels assembled from both mutant and WT subunits. All channel types except WT showed a marked gain-of-function in voltage activation and a smaller decrease-of-function in single-channel conductance, …
Urinary Tract Infections Trigger Synucleinopathy Via The Innate Immune Response, Wouter Peelaerts, Scott J Hultgren, Tom J Hannan, Et Al.
Urinary Tract Infections Trigger Synucleinopathy Via The Innate Immune Response, Wouter Peelaerts, Scott J Hultgren, Tom J Hannan, Et Al.
2020-Current year OA Pubs
Symptoms in the urogenital organs are common in multiple system atrophy (MSA), also in the years preceding the MSA diagnosis. It is unknown how MSA is triggered and these observations in prodromal MSA led us to hypothesize that synucleinopathy could be triggered by infection of the genitourinary tract causing ɑ-synuclein (ɑSyn) to aggregate in peripheral nerves innervating these organs. As a first proof that peripheral infections could act as a trigger in MSA, this study focused on lower urinary tract infections (UTIs), given the relevance and high frequency of UTIs in prodromal MSA, although other types of infection might also …
Expanded Directly Binds Conserved Regions Of Fat To Restrain Growth Via The Hippo Pathway, Alexander D Fulford, Leonie Enderle, Jannette Rusch, Didier Hodzic, Maxine V Holder, Alex Earl, Robin Hyunseo Oh, Nicolas Tapon, Helen Mcneill
Expanded Directly Binds Conserved Regions Of Fat To Restrain Growth Via The Hippo Pathway, Alexander D Fulford, Leonie Enderle, Jannette Rusch, Didier Hodzic, Maxine V Holder, Alex Earl, Robin Hyunseo Oh, Nicolas Tapon, Helen Mcneill
2020-Current year OA Pubs
The Hippo pathway is a conserved and critical regulator of tissue growth. The FERM protein Expanded is a key signaling hub that promotes activation of the Hippo pathway, thereby inhibiting the transcriptional co-activator Yorkie. Previous work identified the polarity determinant Crumbs as a primary regulator of Expanded. Here, we show that the giant cadherin Fat also regulates Expanded directly and independently of Crumbs. We show that direct binding between Expanded and a highly conserved region of the Fat cytoplasmic domain recruits Expanded to the apicolateral junctional zone and stabilizes Expanded. In vivo deletion of Expanded binding regions in Fat causes …
Tumor-Derived Interleukin-1Α And Leukemia Inhibitory Factor Promote Extramedullary Hematopoiesis, Derek A. G. Barisas, Ashraf Ul Kabir, Jun Wu, Karen Krchma, Minseo Kim, Madhav Subramanian, Bernd H. Zinselmeyer, Colin L. Stewart, Kyunghee Choi
Tumor-Derived Interleukin-1Α And Leukemia Inhibitory Factor Promote Extramedullary Hematopoiesis, Derek A. G. Barisas, Ashraf Ul Kabir, Jun Wu, Karen Krchma, Minseo Kim, Madhav Subramanian, Bernd H. Zinselmeyer, Colin L. Stewart, Kyunghee Choi
2020-Current year OA Pubs
Extramedullary hematopoiesis (EMH) expands hematopoietic capacity outside of the bone marrow in response to inflammatory conditions, including infections and cancer. Because of its inducible nature, EMH offers a unique opportunity to study the interaction between hematopoietic stem and progenitor cells (HSPCs) and their niche. In cancer patients, the spleen frequently serves as an EMH organ and provides myeloid cells that may worsen pathology. Here, we examined the relationship between HSPCs and their splenic niche in EMH in a mouse breast cancer model. We identify tumor produced IL-1α and leukemia inhibitory factor (LIF) acting on splenic HSPCs and splenic niche cells, …
Capsular Polysaccharide Inhibits Vaccine-Induced O-Antigen Antibody Binding And Function Across Both Classical And Hypervirulent K2:O1 Strains Of Klebsiella Pneumoniae, Paeton L. Wantuch, Cory J. Knoot, Lloyd S. Robinson, Evgeny Vinogradov, Nichollas E. Scott, Christian M. Harding, David A. Rosen
Capsular Polysaccharide Inhibits Vaccine-Induced O-Antigen Antibody Binding And Function Across Both Classical And Hypervirulent K2:O1 Strains Of Klebsiella Pneumoniae, Paeton L. Wantuch, Cory J. Knoot, Lloyd S. Robinson, Evgeny Vinogradov, Nichollas E. Scott, Christian M. Harding, David A. Rosen
2020-Current year OA Pubs
Klebsiella pneumoniae presents as two circulating pathotypes: classical K. pneumoniae (cKp) and hypervirulent K. pneumoniae (hvKp). Classical isolates are considered urgent threats due to their antibiotic resistance profiles, while hvKp isolates have historically been antibiotic susceptible. Recently, however, increased rates of antibiotic resistance have been observed in both hvKp and cKp, further underscoring the need for preventive and effective immunotherapies. Two distinct surface polysaccharides have gained traction as vaccine candidates against K. pneumoniae: capsular polysaccharide and the O-antigen of lipopolysaccharide. While both targets have practical advantages and disadvantages, it remains unclear which of these antigens included in a vaccine would …
Deep Learning Based On Co-Registered Ultrasound And Photoacoustic Imaging Improves The Assessment Of Rectal Cancer Treatment Response, Yixiao Lin, Sitai Kou, Haolin Nie, Hongbo Luo, Ahmed Eltahir, Will Chapman Jr., Steven Hunt, Matthew Mutch, Quing Zhu
Deep Learning Based On Co-Registered Ultrasound And Photoacoustic Imaging Improves The Assessment Of Rectal Cancer Treatment Response, Yixiao Lin, Sitai Kou, Haolin Nie, Hongbo Luo, Ahmed Eltahir, Will Chapman Jr., Steven Hunt, Matthew Mutch, Quing Zhu
2020-Current year OA Pubs
Identifying complete response (CR) after rectal cancer preoperative treatment is critical to deciding subsequent management. Imaging techniques, including endorectal ultrasound and MRI, have been investigated but have low negative predictive values. By imaging post-treatment vascular normalization using photoacoustic microscopy, we hypothesize that co-registered ultrasound and photoacoustic imaging will better identify complete responders. In this study, we used
Comparing Genomic And Epigenomic Features Across Species Using The Washu Comparative Epigenome Browser, Xiaoyu Zhuo, Silas Hsu, Deepak Purushotham, Prashant Kumar Kuntala, Jessica K Harrison, Alan Y Du, Samuel Chen, Daofeng Li, Ting Wang
Comparing Genomic And Epigenomic Features Across Species Using The Washu Comparative Epigenome Browser, Xiaoyu Zhuo, Silas Hsu, Deepak Purushotham, Prashant Kumar Kuntala, Jessica K Harrison, Alan Y Du, Samuel Chen, Daofeng Li, Ting Wang
2020-Current year OA Pubs
Genome browsers have become an intuitive and critical tool to visualize and analyze genomic features and data. Conventional genome browsers display data/annotations on a single reference genome/assembly; there are also genomic alignment viewer/browsers that help users visualize alignment, mismatch, and rearrangement between syntenic regions. However, there is a growing need for a comparative epigenome browser that can display genomic and epigenomic data sets across different species and enable users to compare them between syntenic regions. Here, we present the WashU Comparative Epigenome Browser. It allows users to load functional genomic data sets/annotations mapped to different genomes and display them over …
Propranolol Reduces Ifn-Γ Driven Pd-L1 Immunosuppression And Improves Anti-Tumour Immunity In Ovarian Cancer, M Falcinelli, G Al-Hity, S Baron, M Mampay, M C Allen, M Samuels, W Jones, C Cilibrasi, Renee L Flaherty, G Giamas, P H Thaker, M S Flint
Propranolol Reduces Ifn-Γ Driven Pd-L1 Immunosuppression And Improves Anti-Tumour Immunity In Ovarian Cancer, M Falcinelli, G Al-Hity, S Baron, M Mampay, M C Allen, M Samuels, W Jones, C Cilibrasi, Renee L Flaherty, G Giamas, P H Thaker, M S Flint
2020-Current year OA Pubs
The immune system plays an important role in controlling epithelial ovarian cancer (EOC). EOC is considered to be a "cold tumour," a tumour that has not triggered a strong response by the immune system. However, tumour infiltrating lymphocytes (TILs) and the expression of programmed cell death ligand (PD-L1) are used as prognostic indicators in EOC. Immunotherapy such as PD-(L)1 inhibitors have shown limited benefit in EOC. Since the immune system is affected by behavioural stress and the beta-adrenergic signalling pathway, this study aimed to explore the impact of propranolol (PRO), a beta-blocker, on anti-tumour immunity in both in vitro and …
Neurosteroids As Stress Modulators And Neurotherapeutics: Lessons From The Retina, Yukitoshi Izumi, Makoto Ishikawa, Toru Nakazawa, Hiroshi Kunikata, Kota Sato, Douglas F. Covey, Charles F. Zorumski
Neurosteroids As Stress Modulators And Neurotherapeutics: Lessons From The Retina, Yukitoshi Izumi, Makoto Ishikawa, Toru Nakazawa, Hiroshi Kunikata, Kota Sato, Douglas F. Covey, Charles F. Zorumski
2020-Current year OA Pubs
Neurosteroids are rapidly emerging as important new therapies in neuropsychiatry, with one such agent, brexanolone, already approved for treatment of postpartum depression, and others on the horizon. These steroids have unique properties, including neuroprotective effects that could benefit a wide range of brain illnesses including depression, anxiety, epilepsy, and neurodegeneration. Over the past 25 years, our group has developed ex vivo rodent models to examine factors contributing to several forms of neurodegeneration in the retina. In the course of this work, we have developed a model of acute closed angle glaucoma that involves incubation of ex vivo retinas under hyperbaric …
Functional Screening Of Lysosomal Storage Disorder Genes Identifies Modifiers Of Alpha-Synuclein Neurotoxicity, Meigen Yu, Hui Ye, Ruth B. De-Paula, Carl Grant Mangleburg, Timothy Wu, Tom V. Lee, Yarong Li, Duc Duong, Bridget Phillips, Carlos Cruchaga, Genevera I. Allen, Nicholas T. Seyfried, Ismael Al-Ramahi, Juan Botas, Joshua M. Shulman
Functional Screening Of Lysosomal Storage Disorder Genes Identifies Modifiers Of Alpha-Synuclein Neurotoxicity, Meigen Yu, Hui Ye, Ruth B. De-Paula, Carl Grant Mangleburg, Timothy Wu, Tom V. Lee, Yarong Li, Duc Duong, Bridget Phillips, Carlos Cruchaga, Genevera I. Allen, Nicholas T. Seyfried, Ismael Al-Ramahi, Juan Botas, Joshua M. Shulman
2020-Current year OA Pubs
Heterozygous variants in the glucocerebrosidase (GBA) gene are common and potent risk factors for Parkinson's disease (PD). GBA also causes the autosomal recessive lysosomal storage disorder (LSD), Gaucher disease, and emerging evidence from human genetics implicates many other LSD genes in PD susceptibility. We have systemically tested 86 conserved fly homologs of 37 human LSD genes for requirements in the aging adult Drosophila brain and for potential genetic interactions with neurodegeneration caused by α-synuclein (αSyn), which forms Lewy body pathology in PD. Our screen identifies 15 genetic enhancers of αSyn-induced progressive locomotor dysfunction, including knockdown of fly homologs of GBA …