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https://www.readbyqxmd.com/read/29031834/dysregulation-of-neurotrophin-signaling-in-the-pathogenesis-of-alzheimer-disease-and-of-alzheimer-disease-in-down-syndrome
#1
REVIEW
Xu-Qiao Chen, Mariko Sawa, William C Mobley
Neurotrophic factors, including the members of the neurotrophin family, play important roles in the development and maintenance of the nervous system. Trophic factor signals must be transmitted over long distances from axons and dendrites to the cell bodies of neurons. A mode of signaling well suited to the challenge of robust long distance signaling is the signaling endosome. We review the biology of signaling endosomes and the "signaling endosome hypothesis". Evidence for disruption of signaling endosome function in disorders of the nervous system is also reviewed...
October 12, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28946567/pet-imaging-of-tau-pathology-and-relationship-to-amyloid-longitudinal-mri-and-cognitive-change-in-down-syndrome-results-from-the-down-syndrome-biomarker-initiative-dsbi
#2
Michael S Rafii, Ana S Lukic, Randolph D Andrews, James Brewer, Robert A Rissman, Stephen C Strother, Miles N Wernick, Craig Pennington, William C Mobley, Seth Ness, Dawn C Matthews
BACKGROUND: Adults with Down syndrome (DS) represent an enriched population for the development of Alzheimer's disease (AD), which could aid the study of therapeutic interventions, and in turn, could benefit from discoveries made in other AD populations. OBJECTIVES: 1) Understand the relationship between tau pathology and age, amyloid deposition, neurodegeneration (MRI and FDG PET), and cognitive and functional performance; 2) detect and differentiate AD-specific changes from DS-specific brain changes in longitudinal MRI...
2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28654545/impact-of-pretransplant-bridging-locoregional-therapy-for-patients-with-hepatocellular-carcinoma-within-milan-criteria-undergoing-liver-transplantation-analysis-of-3601-patients-from-the-us-multicenter-hcc-transplant-consortium
#3
MULTICENTER STUDY
Vatche G Agopian, Michael P Harlander-Locke, Richard M Ruiz, Goran B Klintmalm, Srinath Senguttuvan, Sander S Florman, Brandy Haydel, Maarouf Hoteit, Matthew H Levine, David D Lee, C Burcin Taner, Elizabeth C Verna, Karim J Halazun, Rita Abdelmessih, Amit D Tevar, Abhinav Humar, Federico Aucejo, William C Chapman, Neeta Vachharajani, Mindie H Nguyen, Marc L Melcher, Trevor L Nydam, Constance Mobley, R Mark Ghobrial, Beth Amundsen, James F Markmann, Alan N Langnas, Carol A Carney, Jennifer Berumen, Alan W Hemming, Debra L Sudan, Johnny C Hong, Joohyun Kim, Michael A Zimmerman, Abbas Rana, Michael L Kueht, Christopher M Jones, Thomas M Fishbein, Ronald W Busuttil
OBJECTIVE: To evaluate the effect of pretransplant bridging locoregional therapy (LRT) on hepatocellular carcinoma (HCC) recurrence and survival after liver transplantation (LT) in patients meeting Milan criteria (MC). SUMMARY BACKGROUND DATA: Pre-LT LRT mitigates tumor progression and waitlist dropout in HCC patients within MC, but data on its impact on post-LT recurrence and survival remain limited. METHODS: Recurrence-free survival and post-LT recurrence were compared among 3601 MC patients with and without bridging LRT utilizing competing risk Cox regression in consecutive patients from 20 US centers (2002-2013)...
September 2017: Annals of Surgery
https://www.readbyqxmd.com/read/28587118/nerve-growth-factor-and-related-substances-a-brief-history-and-an-introduction-to-the-international-ngf-meeting-series
#4
EDITORIAL
Ralph A Bradshaw, William Mobley, Robert A Rush
Nerve growth factor (NGF) is a protein whose importance to research and its elucidation of fundamental mechanisms in cell and neurobiology far outstrips its basic physiological roles. It was the first of a broad class of cell regulators, largely acting through autocrine and paracrine interactions which will be described herein. It was of similar significance in establishing the identity and unique roles of neurotrophic factors in the development and maintenance of the peripheral and central nervous systems...
May 26, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28416568/pharmacological-and-toxicological-properties-of-the-potent-oral-%C3%AE-secretase-modulator-bpn-15606
#5
Steven L Wagner, Kevin D Rynearson, Steven K Duddy, Can Zhang, Phuong D Nguyen, Ann Becker, Uyen Vo, Deborah Masliah, Louise Monte, Justin B Klee, Corinne M Echmalian, Weiming Xia, Luisa Quinti, Graham Johnson, Jiunn H Lin, Doo Y Kim, William C Mobley, Robert A Rissman, Rudolph E Tanzi
Alzheimer's disease (AD) is characterized neuropathologically by an abundance of 1) neuritic plaques, which are primarily composed of a fibrillar 42-amino-acid amyloid-β peptide (Aβ), as well as 2) neurofibrillary tangles composed of aggregates of hyperphosporylated tau. Elevations in the concentrations of the Aβ42 peptide in the brain, as a result of either increased production or decreased clearance, are postulated to initiate and drive the AD pathologic process. We initially introduced a novel class of bridged aromatics referred tγ-secretase modulatoro as γ-secretase modulators that inhibited the production of the Aβ42 peptide and to a lesser degree the Aβ40 peptide while concomitantly increasing the production of the carboxyl-truncated Aβ38 and Aβ37 peptides...
July 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28342823/evidence-that-increased-kcnj6-gene-dose-is-necessary-for-deficits-in-behavior-and-dentate-gyrus-synaptic-plasticity-in-the-ts65dn-mouse-model-of-down-syndrome
#6
Alexander M Kleschevnikov, Jessica Yu, Jeesun Kim, Larisa V Lysenko, Zheng Zeng, Y Eugene Yu, William C Mobley
Down syndrome (DS), trisomy 21, is caused by increased dose of genes present on human chromosome 21 (HSA21). The gene-dose hypothesis argues that a change in the dose of individual genes or regulatory sequences on HSA21 is necessary for creating DS-related phenotypes, including cognitive impairment. We focused on a possible role for Kcnj6, the gene encoding Kir3.2 (Girk2) subunits of a G-protein-coupled inwardly-rectifying potassium channel. This gene resides on a segment of mouse Chromosome 16 that is present in one extra copy in the genome of the Ts65Dn mouse, a well-studied genetic model of DS...
July 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28040097/hospital-based-multidisciplinary-youth-mentoring-and-medical-exposure-program-positively-influences-and-reinforces-health-care-career-choice-the-reach-one-each-one-program-early-experience
#7
Omar K Danner, Carl Lokko, Felicia Mobley, Montreka Dansby, Michael Maze, Brene' Bradley, Elizabeth Williams, Leslie Ray Matthews, Emma Harrington, Lisa Mack, Clarence Clark, Ken Wilson, Derrick Beech, Sheryl Heron, Ed Childs
BACKGROUND: According to the National Center for Educational Statistics, underrepresented minorities (URMs) are more likely to leave science, technology, engineering and mathematics (STEM) fields at higher rates than their peers during undergraduate studies. Many institutions of higher learning have implemented pipeline programs aimed at preparing and inspiring high school and college aged students in select careers in health sciences with varying levels of success. Research has shown that a health care workforce that mirrors the community they serve is more effective in reducing health disparities and increasing positive health outcomes...
April 2017: American Journal of Surgery
https://www.readbyqxmd.com/read/27998093/cucurbit-7-uril-tetramethylrhodamine-conjugate-for-direct-sensing-and-cellular-imaging
#8
Andrew T Bockus, Lauren C Smith, Amy G Grice, Omar A Ali, Carolyn C Young, William Mobley, Ashley Leek, James L Roberts, Brittany Vinciguerra, Lyle Isaacs, Adam R Urbach
This paper describes the design and synthesis of a conjugate (Q7R) comprising the synthetic host cucurbit[7]uril (Q7) linked to the fluorescent dye tetramethylrhodamine (TMR), and the characterization of its optical and guest-binding properties as well as its cellular uptake. Q7R was synthesized in two steps from monofunctionalized azidobutyl-Q7 and NHS-activated TMR. The fluorescence of Q7R is quenched upon guest binding, and this observable was used to determine equilibrium dissociation constant (Kd) values...
December 21, 2016: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/27926645/association-between-sleep-disordered-breathing-and-hypertensive-disorders-of-pregnancy-and-gestational-diabetes-mellitus
#9
MULTICENTER STUDY
Francesca L Facco, Corette B Parker, Uma M Reddy, Robert M Silver, Matthew A Koch, Judette M Louis, Robert C Basner, Judith H Chung, Chia-Ling Nhan-Chang, Grace W Pien, Susan Redline, William A Grobman, Deborah A Wing, Hyagriv N Simhan, David M Haas, Brian M Mercer, Samuel Parry, Daniel Mobley, Shannon Hunter, George R Saade, Frank P Schubert, Phyllis C Zee
OBJECTIVE: To estimate whether sleep-disordered breathing during pregnancy is a risk factor for the development of hypertensive disorders of pregnancy and gestational diabetes mellitus (GDM). METHODS: In this prospective cohort study, nulliparous women underwent in-home sleep-disordered breathing assessments in early (6-15 weeks of gestation) and midpregnancy (22-31 weeks of gestation). Participants and health care providers were blinded to the sleep test results...
January 2017: Obstetrics and Gynecology
https://www.readbyqxmd.com/read/27789459/mouse-based-genetic-modeling-and-analysis-of-down-syndrome
#10
REVIEW
Zhuo Xing, Yichen Li, Annie Pao, Abigail S Bennett, Benjamin Tycko, William C Mobley, Y Eugene Yu
INTRODUCTION: Down syndrome (DS), caused by human trisomy 21 (Ts21), can be considered as a prototypical model for understanding the effects of chromosomal aneuploidies in other diseases. Human chromosome 21 (Hsa21) is syntenically conserved with three regions in the mouse genome. SOURCES OF DATA: A review of recent advances in genetic modeling and analysis of DS. Using Cre/loxP-mediated chromosome engineering, a substantial number of new mouse models of DS have recently been generated, which facilitates better understanding of disease mechanisms in DS...
December 2016: British Medical Bulletin
https://www.readbyqxmd.com/read/27701794/gabaergic-hyperinnervation-of-dentate-granule-cells-in-the-ts65dn-mouse-model-of-down-syndrome-exploring-the-role-of-app
#11
Fatemeh S Mojabi, Atoossa Fahimi, Shahrzad Moghadam, Sarah Moghadam, M Windy McNerneny, Ravikumar Ponnusamy, Alexander Kleschevnikov, William C Mobley, Ahmad Salehi
It has been suggested that increased GABAergic innervation in the hippocampus plays a significant role in cognitive dysfunction in Down syndrome (DS). Bolstering this notion, are studies linking hyper-innervation of the dentate gyrus (DG) by GABAergic terminals to failure in LTP induction in the Ts65Dn mouse model of DS. Here, we used extensive morphometrical methods to assess the status of GABAergic interneurons in the DG of young and old Ts65Dn mice and their 2N controls. We detected an age-dependent increase in GABAergic innervation of dentate granule cells (DGCs) in Ts65Dn mice...
December 2016: Hippocampus
https://www.readbyqxmd.com/read/27601642/tric-subunits-enhance-bdnf-axonal-transport-and-rescue-striatal-atrophy-in-huntington-s-disease
#12
Xiaobei Zhao, Xu-Qiao Chen, Eugene Han, Yue Hu, Paul Paik, Zhiyong Ding, Julia Overman, Alice L Lau, Sarah H Shahmoradian, Wah Chiu, Leslie M Thompson, Chengbiao Wu, William C Mobley
Corticostriatal atrophy is a cardinal manifestation of Huntington's disease (HD). However, the mechanism(s) by which mutant huntingtin (mHTT) protein contributes to the degeneration of the corticostriatal circuit is not well understood. We recreated the corticostriatal circuit in microfluidic chambers, pairing cortical and striatal neurons from the BACHD model of HD and its WT control. There were reduced synaptic connectivity and atrophy of striatal neurons in cultures in which BACHD cortical and striatal neurons were paired...
September 20, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27506233/single-figure-publications-towards-a-novel-alternative-format-for-scholarly-communication
#13
COMMENT
Long Do, William Mobley
The single figure publication is a novel, efficient format by which to communicate scholarly advances. It will serve as a forerunner of the nano-publication, a modular unit of information critical for machine-driven data aggregation and knowledge integration.
2015: F1000Research
https://www.readbyqxmd.com/read/27302127/dementia-in-down-s-syndrome
#14
REVIEW
Clive Ballard, William Mobley, John Hardy, Gareth Williams, Anne Corbett
Down's syndrome is the most common genetic cause of learning difficulties, and individuals with this condition represent the largest group of people with dementia under the age of 50 years. Genetic drivers result in a high frequency of Alzheimer's pathology in these individuals, evident from neuroimaging, biomarker, and neuropathological findings, and a high incidence of cognitive decline and dementia. However, cognitive assessment is challenging, and diagnostic methods have not been fully validated for use in these patients; hence, early diagnosis remains difficult...
May 2016: Lancet Neurology
https://www.readbyqxmd.com/read/27256764/distance-to-testing-sites-and-its-association-with-timing-of-hiv-diagnosis
#15
Anna B Cope, Kimberly A Powers, Marc L Serre, Veronica Escamilla, Michael E Emch, Peter A Leone, Victoria L Mobley, William C Miller
Early HIV diagnosis enables prompt treatment initiation, thereby contributing to decreased morbidity, mortality, and transmission. We aimed to describe the association between distance from residence to testing sites and HIV disease stage at diagnosis. Using HIV surveillance data, we identified all new HIV diagnoses made at publicly funded testing sites in central North Carolina during 2005-2013. Early-stage HIV was defined as acute HIV (antibody-negative test with a positive HIV RNA) or recent HIV (normalized optical density <0...
November 2016: AIDS Care
https://www.readbyqxmd.com/read/27207807/correction-exosome-like-nanoparticles-from-intestinal-mucosal-cells-carry-prostaglandin-e2-and-suppress-activation-of-liver-nkt-cells
#16
Zhong-Bin Deng, Xiaoying Zhuang, Songwen Ju, Xiaoyu Xiang, Jingyao Mu, Yuelong Liu, Hong Jiang, Lifeng Zhang, James Mobley, Craig McClain, Wenke Feng, William Grizzle, Jun Yan, Donald Miller, Mitchell Kronenberg, Huang-Ge Zhang
No abstract text is available yet for this article.
June 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27195491/a-syntenic-cross-species-aneuploidy-genetic-screen-links-rcan1-expression-to-%C3%AE-cell-mitochondrial-dysfunction-in-type-2-diabetes
#17
Heshan Peiris, Michael D Duffield, Joao Fadista, Claire F Jessup, Vinder Kashmir, Amanda J Genders, Sean L McGee, Alyce M Martin, Madiha Saiedi, Nicholas Morton, Roderick Carter, Michael A Cousin, Alexandros C Kokotos, Nikolay Oskolkov, Petr Volkov, Tertius A Hough, Elizabeth M C Fisher, Victor L J Tybulewicz, Jorge Busciglio, Pinar E Coskun, Ann Becker, Pavel V Belichenko, William C Mobley, Michael T Ryan, Jeng Yie Chan, D Ross Laybutt, P Toby Coates, Sijun Yang, Charlotte Ling, Leif Groop, Melanie A Pritchard, Damien J Keating
Type 2 diabetes (T2D) is a complex metabolic disease associated with obesity, insulin resistance and hypoinsulinemia due to pancreatic β-cell dysfunction. Reduced mitochondrial function is thought to be central to β-cell dysfunction. Mitochondrial dysfunction and reduced insulin secretion are also observed in β-cells of humans with the most common human genetic disorder, Down syndrome (DS, Trisomy 21). To identify regions of chromosome 21 that may be associated with perturbed glucose homeostasis we profiled the glycaemic status of different DS mouse models...
May 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27064279/amyloid-precursor-protein-mediated-endocytic-pathway-disruption-induces-axonal-dysfunction-and-neurodegeneration
#18
Wei Xu, April M Weissmiller, Joseph A White, Fang Fang, Xinyi Wang, Yiwen Wu, Matthew L Pearn, Xiaobei Zhao, Mariko Sawa, Shengdi Chen, Shermali Gunawardena, Jianqing Ding, William C Mobley, Chengbiao Wu
The endosome/lysosome pathway is disrupted early in the course of both Alzheimer's disease (AD) and Down syndrome (DS); however, it is not clear how dysfunction in this pathway influences the development of these diseases. Herein, we explored the cellular and molecular mechanisms by which endosomal dysfunction contributes to the pathogenesis of AD and DS. We determined that full-length amyloid precursor protein (APP) and its β-C-terminal fragment (β-CTF) act though increased activation of Rab5 to cause enlargement of early endosomes and to disrupt retrograde axonal trafficking of nerve growth factor (NGF) signals...
May 2, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27023444/an-anti-%C3%AE-amyloid-vaccine-for-treating-cognitive-deficits-in-a-mouse-model-of-down-syndrome
#19
Pavel V Belichenko, Rime Madani, Lorianne Rey-Bellet, Maria Pihlgren, Ann Becker, Adeline Plassard, Stephanie Vuillermot, Valérie Giriens, Rachel L Nosheny, Alexander M Kleschevnikov, Janice S Valletta, Sara K S Bengtsson, Gordon R Linke, Michael T Maloney, David T Hickman, Pedro Reis, Anne Granet, Dorin Mlaki, Maria Pilar Lopez-Deber, Long Do, Nishant Singhal, Eliezer Masliah, Matthew L Pearn, Andrea Pfeifer, Andreas Muhs, William C Mobley
In Down syndrome (DS) or trisomy of chromosome 21, the β-amyloid (Aβ) peptide product of the amyloid precursor protein (APP) is present in excess. Evidence points to increased APP gene dose and Aβ as playing a critical role in cognitive difficulties experienced by people with DS. Particularly, Aβ is linked to the late-life emergence of dementia as associated with neuropathological markers of Alzheimer's disease (AD). At present, no treatment targets Aβ-related pathogenesis in people with DS. Herein we used a vaccine containing the Aβ 1-15 peptide embedded into liposomes together with the adjuvant monophosphoryl lipid A (MPLA)...
2016: PloS One
https://www.readbyqxmd.com/read/26664707/questioned-validity-of-gene-expression-dysregulated-domains-in-down-s-syndrome
#20
Long H Do, William C Mobley, Nishant Singhal
Recently, in studies examining fibroblasts obtained from the tissues of one set of monozygotic twins (i.e. fetuses derived from the same egg) discordant for trisomy 21 (Down syndrome; DS), Letourneau et al., ( )reported the presence of a defined pattern of dysregulation within specific genomic domains they referred to as Gene Expression Dysregulated Domains (GEDDs). GEDDs were described as alternating segments of increased or decreased gene expression affecting all chromosomes. Strikingly, GEDDs in fibroblasts were largely conserved in induced pluripotent cells (iPSCs) generated from the twin's fibroblasts as well as in fibroblasts from the Ts65Dn mouse model of DS...
2015: F1000Research
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