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Alternative Splicing In Vertebrate Photoreceptors And Mechanisms Underlying Retinitis Pigmentosa, Jesse C. Sundar Jan 2019

Alternative Splicing In Vertebrate Photoreceptors And Mechanisms Underlying Retinitis Pigmentosa, Jesse C. Sundar

Graduate Theses, Dissertations, and Problem Reports (ETD)

RNA binding proteins (RBPs) have emerged as important regulators of gene expression. RBPs typically contain RNA binding domains that recognize a specific sequence and/or structural motifs within the RNA. This allows them to modulate metabolism of RNAs in several possible ways including regulation of alternative splicing and processing, polyadenylation, translocation, localization, modification, stability, or translation. Previous studies have shown the Musashi (MSI) RBP family to be highly expressed in the retina, and more specifically, photoreceptors, but the importance of this expression remains largely unknown. We identified the MSI proteins as potential regulators of alternative exon splicing in murine photoreceptors. We …


Domain Adaptation And Privileged Information For Visual Recognition, Saeid Motiian Jan 2019

Domain Adaptation And Privileged Information For Visual Recognition, Saeid Motiian

Graduate Theses, Dissertations, and Problem Reports (ETD)

The automatic identification of entities like objects, people or their actions in visual data, such as images or video, has significantly improved, and is now being deployed in access control, social media, online retail, autonomous vehicles, and several other applications. This visual recognition capability leverages supervised learning techniques, which require large amounts of labeled training data from the target distribution representative of the particular task at hand. However, collecting such training data might be expensive, require too much time, or even be impossible. In this work, we introduce several novel approaches aiming at compensating for the lack of target training …


Pulmonary Toxicity And Lung Tumorigenic Potential Of Surrogate Metal Oxides In Gas Metal Arc Welding–Stainless Steel Fume: Iron As A Primary Mediator Versus Chromium And Nickel, Lauryn M. Falcone, Aaron Erdely, Rebecca Salmen, Michael Keane, Lori Battelli, Vamsi Kodali, Aleksandr B. Stefaniak, Michael L. Kashon, James M. Antonini, Patti C. Zeidler-Erdely Dec 2018

Pulmonary Toxicity And Lung Tumorigenic Potential Of Surrogate Metal Oxides In Gas Metal Arc Welding–Stainless Steel Fume: Iron As A Primary Mediator Versus Chromium And Nickel, Lauryn M. Falcone, Aaron Erdely, Rebecca Salmen, Michael Keane, Lori Battelli, Vamsi Kodali, Aleksandr B. Stefaniak, Michael L. Kashon, James M. Antonini, Patti C. Zeidler-Erdely

Faculty & Staff Scholarship

In 2017, the International Agency for Research on Cancer classified welding fumes as “car- cinogenic to humans” (Group 1). Both mild steel (MS) welding, where fumes lack carcino- genic chromium and nickel, and stainless steel (SS) increase lung cancer risk in welders; therefore, further research to better understand the toxicity of the individual metals is needed. The objectives were to (1) compare the pulmonary toxicity of chromium (as Cr(III) oxide [Cr2O3] and Cr (VI) calcium chromate [CaCrO4]), nickel [II] oxide (NiO), iron [III] oxide (Fe2O3), and gas metal arc welding-SS (GMAW-SS) fume; and (2) determine if these metal oxides can …


Hypoxic Preconditioning Attenuates Reoxygenation-Induced Skeletal Muscle Dysfunction In Aged Pulmonary Tnf-Α Overexpressing Mice, China-Chen Chuang, Tingyang Zhou, Mark Olfert, Li Zuo Dec 2018

Hypoxic Preconditioning Attenuates Reoxygenation-Induced Skeletal Muscle Dysfunction In Aged Pulmonary Tnf-Α Overexpressing Mice, China-Chen Chuang, Tingyang Zhou, Mark Olfert, Li Zuo

Faculty & Staff Scholarship

No abstract provided.


Low Sucrose, Omega-3 Enriched Diet Has Region-Specific Effects On Neuroinflammation And Synaptic Function Markers In A Mouse Model Of Doxorubicin-Based Chemotherapy, Tonya S. Orchard, Monica M. Gaudier-Diaz, Panchita Phuwamongkolwiwat-Chu, Rebecca Andridge, Maryam B. Lustberg, Joshua Bomser, Rachel M. Cole, Martha A. Belury, A. Courtney Devries Dec 2018

Low Sucrose, Omega-3 Enriched Diet Has Region-Specific Effects On Neuroinflammation And Synaptic Function Markers In A Mouse Model Of Doxorubicin-Based Chemotherapy, Tonya S. Orchard, Monica M. Gaudier-Diaz, Panchita Phuwamongkolwiwat-Chu, Rebecca Andridge, Maryam B. Lustberg, Joshua Bomser, Rachel M. Cole, Martha A. Belury, A. Courtney Devries

Clinical and Translational Science Institute

Chemotherapeutic agents such as doxorubicin may negatively affect long-term brain functioning in cancer survivors; neuroinflammation may play a causal role. Dietary approaches that reduce inflammation, such as lowering sucrose and increasing eicosapentaenoic acid plus docosahexaenoic acid (EPA + DHA), may attenuate chemotherapy-induced neuroinflammation and synaptic damage, thereby improving quality of life. Ovariectomized, C57BL/6 mice were assigned to a chemotherapy (9 mg/kg doxorubicin + 90 mg/kg cyclophosphamide) or vehicle two-injection regimen, with injections two and four weeks after starting diets. In Study 1, mice received low sucrose diets with EPA + DHA or No EPA + DHA for four to six …


Human Breast Cancer Xenograft Model Implicates Peroxisome Proliferator-Activated Receptor Signaling As Driver Of Cancer-Induced Muscle Fatigue, Hannah E. Wilson, Kacey K. Rhodes, Daniel Rodriguez, Ikttesh Chahal, David A. Stanton, Joseph Bohlen, Mary Davis, Aniello M. Infante, Hannah Hazard-Jenkins, David J. Klinke, Elena N. Pugacheva, Emidio E. Pistilli Dec 2018

Human Breast Cancer Xenograft Model Implicates Peroxisome Proliferator-Activated Receptor Signaling As Driver Of Cancer-Induced Muscle Fatigue, Hannah E. Wilson, Kacey K. Rhodes, Daniel Rodriguez, Ikttesh Chahal, David A. Stanton, Joseph Bohlen, Mary Davis, Aniello M. Infante, Hannah Hazard-Jenkins, David J. Klinke, Elena N. Pugacheva, Emidio E. Pistilli

Clinical and Translational Science Institute

Purpose: This study tested the hypothesis that a patient-derived orthotopic xenograft (PDOX) model would recapitulate the common clinical phenomenon of breast cancer–induced skeletal muscle (SkM) fatigue in the absence of muscle wasting. This study additionally sought to identify drivers of this condition to facilitate the development of therapeutic agents for patients with breast cancer experiencing muscle fatigue. Experimental Design: Eight female BC-PDOX–bearing mice were produced via transplantation of tumor tissue from 8 female patients with breast cancer. Individual hind limb muscles from BC-PDOX mice were isolated at euthanasia for RNA-sequencing, gene and protein analyses, and an ex vivo muscle contraction …


Permeability Changes And Effect Of Chemotherapy In Brain Adjacent To Tumor In An Experimental Model Of Metastatic Brain Tumor From Breast Cancer, Afroz S. Mohammad, Chris E. Adkins, Neal Shah, Rawaa Aljammal, Jessica I. G. Griffith, Rachel M. Tallman, Katherine L. Jarrell, Paul R. Lockman Dec 2018

Permeability Changes And Effect Of Chemotherapy In Brain Adjacent To Tumor In An Experimental Model Of Metastatic Brain Tumor From Breast Cancer, Afroz S. Mohammad, Chris E. Adkins, Neal Shah, Rawaa Aljammal, Jessica I. G. Griffith, Rachel M. Tallman, Katherine L. Jarrell, Paul R. Lockman

Clinical and Translational Science Institute

Background: Brain tumor vasculature can be significantly compromised and leakier than that of normal brain blood vessels. Little is known if there are vascular permeability alterations in the brain adjacent to tumor (BAT). Changes in BAT permeability may also lead to increased drug permeation in the BAT, which may exert toxicity on cells of the central nervous system. Herein, we studied permeation changes in BAT using quantitative fluorescent microscopy and autoradiography, while the effect of chemotherapy within the BAT region was determined by staining for activated astrocytes. Methods: Human metastatic breast cancer cells (MDA-MB-231Br) were injected into left ventricle of …


Gradual Common Carotid Artery Occlusion As A Novel Model For Cerebrovascular Hypoperfusion, Dominic D. Quintana, Xuefang Ren, Heng Hu, Elizabeth B. Engler-Chiurazzi, Stephanie L. Rellick, Sara E. Lewis, Jessica M. Povroznik, James W. Simpkins, Mohammad Alvi Dec 2018

Gradual Common Carotid Artery Occlusion As A Novel Model For Cerebrovascular Hypoperfusion, Dominic D. Quintana, Xuefang Ren, Heng Hu, Elizabeth B. Engler-Chiurazzi, Stephanie L. Rellick, Sara E. Lewis, Jessica M. Povroznik, James W. Simpkins, Mohammad Alvi

Clinical and Translational Science Institute

Chronic cerebrovascular hypoperfusion results in vascular dementia and increases predisposition to lacunar infarcts. However, there are no suitable animal models. In this study, we developed a novel model for chronic irreversible cerebral hypoperfusion in mice. Briefly, an ameroid constrictor was placed on the right carotid artery to gradually occlude the vessel, while a microcoil was placed on the left carotid artery to prevent compensation of the blood flow. This procedure resulted in a gradual hypoperfusion developing over a period of 34 days with no cerebral blood flow recovery. Histological analysis of the brain revealed neuronal and axonal degeneration as well …


Oxygen-Induced Leakage Of Spin Polarization In Overhauser- Enhanced Magnetic Resonance Imaging: Application For Oximetry In Tumors, Artem A. Gorodetskii, Timothy D. Eubank, Benoit Driesschaert, Martin Poncelet, Emily Ellis, Valery V. Khramtsov, Andrey A. Bobko Dec 2018

Oxygen-Induced Leakage Of Spin Polarization In Overhauser- Enhanced Magnetic Resonance Imaging: Application For Oximetry In Tumors, Artem A. Gorodetskii, Timothy D. Eubank, Benoit Driesschaert, Martin Poncelet, Emily Ellis, Valery V. Khramtsov, Andrey A. Bobko

Clinical and Translational Science Institute

Overhauser-enhanced Magnetic Resonance Imaging (OMRI) is a double resonance technique applied for oxygen imaging in aqueous samples and biological tissues. In this report, we present an improved OMRI approach of oxygen measurement using the single line “Finland” trityl spin probe. Compared to a traditional approach, we introduced an additional mechanism of leakage of spin polarization due to an interaction of a spin system with oxygen. The experimental comparison of the new approach with an oxygen-dependent leakage factor to a traditional approach performed in phantom samples in vitro, and mouse tumor model in vivo, shows improved accuracy of determination of oxygen …


Populist Placemaking: Grounds For Open Government-Citizen Spatial Regulating Discourse, Michael N. Widener Dec 2018

Populist Placemaking: Grounds For Open Government-Citizen Spatial Regulating Discourse, Michael N. Widener

West Virginia Law Review

No abstract provided.


Privacy Spaces, Bert-Jaap Koops Dec 2018

Privacy Spaces, Bert-Jaap Koops

West Virginia Law Review

Privacy literature contains conceptualizations of privacy in relation to role-playing and identity construction, and in relation to access control and boundary-management. In this paper, I combine both strands to introduce the concept of privacy spaces: spaces in which you can play, in your own way, the relevant role(s) you have in social life. Drawing from privacy conceptions in legal scholarship, philosophy, sociology, anthropology, human geography, and psychology, a systematic overview of traditional privacy spaces is offered, including mental bubbles, the body, personal space, personal writings, the home, private conversation space, cars, stalls, intimacy bubbles, professional black boxes, coffee house spaces, …


Geographic Discrimination: Of Place, Space, Hillbillies, And Home, William Rhee, Stephen C. Scott Dec 2018

Geographic Discrimination: Of Place, Space, Hillbillies, And Home, William Rhee, Stephen C. Scott

West Virginia Law Review

This Essay explores the two-sided challenge of geographic discrimination, where U.S. citizens receive disparate treatment from other citizens or the government solely because of where they live or self-identify as home, through the interdisciplinary concepts of space, place, and distance; and an original examination of discrimination against Appalachians. Such disparate treatment is unavoidable and even arguably politically correct. Where we call home matters in a number of legitimate ways to include our access to jobs and services, culture, educational opportunities, and other basic human capabilities. Although technology has increased individual mobility more than ever before, a majority of Americans nevertheless …


Commons: Can This Be The Name Of ‘Thirdness’? (Revised), Roger A. Lohmann Nov 2018

Commons: Can This Be The Name Of ‘Thirdness’? (Revised), Roger A. Lohmann

Faculty & Staff Scholarship

In 1995, a journal article asked if 'commons' might be the name of 'thirdness'. In this revision of that article the question is renewed and reintroduced. The concept of the commons and common goods still offer satisfactory ways to label and characterize voluntary action outside markets, states and households. Theory is said to be a problem of language. Language creativity, including the coining of various new terms is a characteristic part of the commons theory of voluntary action. The remaining challenge is how the concept of the commons can relate to the other side of the third sector - the …


Dialogues On Voluntary Action And New Commons, Roger A. Lohmann Nov 2018

Dialogues On Voluntary Action And New Commons, Roger A. Lohmann

Faculty & Staff Scholarship

This volume contains a suite of seven one-act plays originating in political and civic themes, voluntary action and new commons, and associated with the 2012 President election.


Building Eden, Roger A. Lohmann Nov 2018

Building Eden, Roger A. Lohmann

Faculty & Staff Scholarship

Ralph Deigh is the most famous vernacular American architect you've never heard of. After a military career spanning two wars and struggles with homelessness and PTSD, he is invited to design an entirely new rural community for the 21st century. Twin disasters (fire and flood) in Dare County, West Virginia, set up the circumstances for him to join with Rosemary Mueller and the wealthy Ohio-based Mueller Foundation and a mysterious group of local Dare County residents led by Adam Sennett, County Clerk of Dare County. Together, they design and build the new town of Eden, West Virginia.

The whole story …


Conditional Knockout Of Shp2 In Erbb2 Transgenic Mice Or Inhibition In Her2-Amplified Breast Cancer Cell Lines Blocks Oncogene Expression And Tumorigenesis, Hua Zhao, Elisha Martin, Fatimah Matalkah, Neal Shah, Alexey Ivanov, J. Michael Ruppert, Paul R. Lockman, Yehenew M. Agazie Nov 2018

Conditional Knockout Of Shp2 In Erbb2 Transgenic Mice Or Inhibition In Her2-Amplified Breast Cancer Cell Lines Blocks Oncogene Expression And Tumorigenesis, Hua Zhao, Elisha Martin, Fatimah Matalkah, Neal Shah, Alexey Ivanov, J. Michael Ruppert, Paul R. Lockman, Yehenew M. Agazie

Clinical and Translational Science Institute

Overexpression of the human epidermal growth factor receptor 2 (HER2) is the cause of HER2- positive breast cancer (BC). Although HER2-inactivating therapies have benefited BC patients, development of resistance and disease recurrence have been the major clinical problems, pointing to a need for alternative therapeutic strategies. For that to happen, proteins that play critical roles in the biology of HER2-induced tumorigenesis have to be identified and characterized. Here, we show that the Src homology phosphotyrosyl phosphatase 2 (Shp2) encoded by the Ptpn11 gene is a requisite for ErbB2-induced tumorigenesis. We report that conditional knockout of Shp2 alleles in the ErbB2 …


A Novel Method For Training Mice In Visuo-Tactile 3-D Object Discrimination And Recognition, Xian Hu, Ogaga Urhie, Kevin Chang, Rachel Hostetler, Ariel Agmon Nov 2018

A Novel Method For Training Mice In Visuo-Tactile 3-D Object Discrimination And Recognition, Xian Hu, Ogaga Urhie, Kevin Chang, Rachel Hostetler, Ariel Agmon

Clinical and Translational Science Institute

Perceiving, recognizing and remembering 3-dimensional (3-D) objects encountered in the environment has a very high survival value; unsurprisingly, this ability is shared among many animal species, including humans. The psychological, psychophysical and neural basis for object perception, discrimination, recognition and memory has been extensively studied in humans, monkeys, pigeons and rodents, but is still far from understood. Nearly all 3-D object recognition studies in the rodent used the “novel object recognition” paradigm, which relies on innate rather than learned behavior; however, this procedure has several important limitations. Recently, investigators have begun to recognize the power of behavioral tasks learned through …


In Vivo Extracellular Ph Mapping Of Tumors Using Electron Paramagnetic Resonance, Denis A. Komarov, Yuki Ichikawa, Kumiko Yamamoto, Neil J. Stewart, Shingo Matsumoto, Hironobu Yasui, Igor A. Kirilyuk, Valery V. Khramtsov, Osamu Inanami, Hiroshi Hirata Nov 2018

In Vivo Extracellular Ph Mapping Of Tumors Using Electron Paramagnetic Resonance, Denis A. Komarov, Yuki Ichikawa, Kumiko Yamamoto, Neil J. Stewart, Shingo Matsumoto, Hironobu Yasui, Igor A. Kirilyuk, Valery V. Khramtsov, Osamu Inanami, Hiroshi Hirata

Clinical and Translational Science Institute

An electron paramagnetic resonance (EPR)- based method for noninvasive three-dimensional extracellular pH mapping was developed using a pH-sensitive nitroxyl radical as an exogenous paramagnetic probe. Fast projection scanning with a constant magnetic field sweep enabled the acquisition of four-dimensional (3D spatial +1D spectral) EPR images within 7.5 min. Three-dimensional maps of pH were reconstructed by processing the pH-dependent spectral information on the images. To demonstrate the proposed method of pH mapping, the progress of extracellular acidosis in tumor-bearing mouse legs was studied. Furthermore, extracellular pH mapping was used to visualize the spatial distribution of acidification in different tumor xenograft mouse …


A Container Reshaped By Its Contents: The Boyndaries Of Language In Craig Thompson's "Habibi", Rebeccah Griffith Nov 2018

A Container Reshaped By Its Contents: The Boyndaries Of Language In Craig Thompson's "Habibi", Rebeccah Griffith

Mountaineer Undergraduate Research Review

Craig Thompson’s graphic novel “Habibi” is an intricate tracing of the lines that shape and separate religion, sexuality, language, possession, and storytelling, both from one another and within their own orders. The main vein of the story runs through the depiction of the physical body as a linguistically translatable unit, and conversely, language as a corporeal entity that operates in the same complex manner as a physical being. This accurately depicts the relationship between language and the physical world outside of stories as well. The storyline is largely based on themes of possession, sexuality and the intermingling of the twoZ …


The Right To Traditional Life: The Struggle For Native Hunting And Fishing Rights, Caleb Pennington Nov 2018

The Right To Traditional Life: The Struggle For Native Hunting And Fishing Rights, Caleb Pennington

Mountaineer Undergraduate Research Review

This research report examines the ongoing struggle for Native American groups to maintain their traditional hunting and fishing rights. Since the establishment of the United States federal government these rights have been continuously eroded through use of congressional legislation, as well as federal court rulings. These decisions have had devastating effects on the economic, social, and spiritual well being of many of these Native American groups. This piece will attempt to provide an accurate chronology of critical events, which has led to the depredation of these rights. In addition, it will provide a possible blueprint unto how the country of …


Full Issue Nov 2018

Full Issue

Mountaineer Undergraduate Research Review

No abstract provided.


Altering Vapor Pressure Of Mimic Pheromone 2-Phenoxyethanol Affects Efficacy Of Trail-Following Behavior In Reticulitermes Sp., Daniel Teoli Nov 2018

Altering Vapor Pressure Of Mimic Pheromone 2-Phenoxyethanol Affects Efficacy Of Trail-Following Behavior In Reticulitermes Sp., Daniel Teoli

Mountaineer Undergraduate Research Review

Over the past several decades, extensive observation and analysis of termite behavior has taken place within the scientific community. One of the topics at the forefront of pertinent research involves exploring the behavioral intricacies of these small eusocial insects (Witting 2007), as well as their specialized reliance on certain chemical secretions [or pheromones] to remain biologically successful within their respective native environments (Matsuura et al. 2010).


Consumption Of Different Caloric Sugar-Sweetened Solutions Alters Tissue Fatty Acid Composition And Lipid Metabolism In Young Female Sprague-Dawley Rats, Kaitlin Mock, Stephanie N. Altman, Joseph C. Gigliotti, Levi Berg, Janet C. Tou Nov 2018

Consumption Of Different Caloric Sugar-Sweetened Solutions Alters Tissue Fatty Acid Composition And Lipid Metabolism In Young Female Sprague-Dawley Rats, Kaitlin Mock, Stephanie N. Altman, Joseph C. Gigliotti, Levi Berg, Janet C. Tou

Mountaineer Undergraduate Research Review

High carbohydrate intake has been reported to contribute to obesity by promoting de novo lipogenesis and metabolic disorders by altering tissue fatty acid composition. The type of caloric sweeteners added to beverages has changed with some sugars suggested to be more lipogenic. Therefore, the study objective was to determine the effect of consuming different types of caloric sugar-sweetened solutions on tissue fatty acid composition and risk of metabolic disorders. Growing female Sprague-Dawley rats were randomly assigned (n=7-8 rats/group) to drink water or water sweetened with 13% (w/v) glucose, sucrose, fructose or high fructose corn syrup 55 (HFCS-55). The rats were …


Effects Of Fixed-Ratio Requirements On Delay Discounting In Rats, Meagan Follett Nov 2018

Effects Of Fixed-Ratio Requirements On Delay Discounting In Rats, Meagan Follett

Mountaineer Undergraduate Research Review

Research on impulsive behavior is often designed to examine the choice between a smaller, more immediate reinforcer versus a larger, more delayed one (e.g., Anderson & Woolverton 2005; Diller, Saunders, & Anderson 2008; Logue 1988). When the delays to both the larger and smaller reinforcers are short, the larger reinforcer is usually chosen. As the delay to the larger reinforcer increases, choice for that reinforcer decreases and switches to choice for the smaller, more immediate reinforcer. This decrease in choice for the larger reinforcer as delay increases is known as delay discounting, as the value of the larger reinforcer is …


What Comic Books And Political Cartoons Reveal About Mexican History, Carolyn Brewer Nov 2018

What Comic Books And Political Cartoons Reveal About Mexican History, Carolyn Brewer

Mountaineer Undergraduate Research Review

History and popular culture have played off one another for centuries. While comic books might certainly seem to be a low-class form of entertainment, lacking the authority of a history textbook, they nonetheless allow the readers to engage in history as they have otherwise never experienced it. Rather than reading descriptions of what happened when the Spanish landed in Mexico, one may read The Cartoon History of the Modern World or Exploring the Americas to see clothing of the time-period as well as how some of the historical characters may have felt. By using comic books and political cartoons, one …


Full Issue Nov 2018

Full Issue

Mountaineer Undergraduate Research Review

No abstract provided.


The Downing Street Irregular: Post-Reichenbach Falls Sherlock Holmes And The Triumph Of Conservative Internationalism, Ben Welton Nov 2018

The Downing Street Irregular: Post-Reichenbach Falls Sherlock Holmes And The Triumph Of Conservative Internationalism, Ben Welton

Mountaineer Undergraduate Research Review

No abstract provided.


Research For Non-Profits, A Service Learning Class In Grantseeking Research, Alyssa Wright Nov 2018

Research For Non-Profits, A Service Learning Class In Grantseeking Research, Alyssa Wright

Faculty & Staff Scholarship

This chapter describes Research for Non-Profits a 300/500 level service-learning course that introduces non-profits and grantseeking while teaching research and information literacy skills. Students in the course create a funder research portfolio for a non-profit client with a funding need. As students draft, revise, and polish the portfolios, they hone their research skills as well as engage with larger information literacy concepts, particularly the value of information, information creation as a process, and how authority is constructed and contextual. The chapter describes the course’s long development road as well as how partnerships were built, not only with the campus center …


Mortality And Associated Morbidities Following Traumatic Brain Injury In Older Medicare Statin Users, Bilal Khokhar, Linda Simoni-Wastila, Julia F. Slejko, Eleanor Perfetto, Min Zhan, Gordon S. Smith Nov 2018

Mortality And Associated Morbidities Following Traumatic Brain Injury In Older Medicare Statin Users, Bilal Khokhar, Linda Simoni-Wastila, Julia F. Slejko, Eleanor Perfetto, Min Zhan, Gordon S. Smith

Clinical and Translational Science Institute

Objective: To assess the relationship between posttraumatic brain injury statin use and (1) mortality and (2) the incidence of associated morbidities, including stroke, depression, and Alzheimer’s disease and related dementias following injury. Setting and Participants: Nested cohort of all Medicare beneficiaries 65 years of age and older who survived a traumatic brain injury (TBI) hospitalization during 2006 through 2010. The final sample comprised 100 515 beneficiaries. Design: Retrospective cohort study of older Medicare beneficiaries. Relative risks (RR) and 95% confidence interval (CI) were obtained using discrete time analysis and generalized estimating equations. Measures: The exposure of interest included monthly atorvastatin, …


Mesenchymal Cox2-Pg Secretome Engages Nr4a-Wnt Signalling Axis In Haematopoietic Progenitors To Suppress Anti-Leukaemia Immunity, Limei Wu, Surya Amarachintha, Jian Xu, Frank Oley Jr., Wei Du Nov 2018

Mesenchymal Cox2-Pg Secretome Engages Nr4a-Wnt Signalling Axis In Haematopoietic Progenitors To Suppress Anti-Leukaemia Immunity, Limei Wu, Surya Amarachintha, Jian Xu, Frank Oley Jr., Wei Du

Clinical and Translational Science Institute

The bone marrow (BM) microenvironment (niche) plays important roles in supporting normal/abnormal haematopoiesis. We investigated the interaction between leukaemic mesenchymal niche and haematopoietic stem and progenitor cells (HSPCs) using the model of Fanconi anaemia (FA), a genetic disorder characterized by BM failure and leukaemia. Healthy donor HSPCs co‐cultured on mesenchymal stromal cells (MSCs) derived from FA patients with acute myeloid leukaemia (AML) exhibited higher human engraftment and myeloid expansion in Non‐obese diabetic severe combined immunodeficiency IL‐2γ−/−/SGM3 recipients. Untargeted metabolomics analysis revealed the progressively elevated prostaglandins (PGs) in the MSCs of FA patients with myelodysplastic syndromes (MDS) and AML. Reduced secretion …