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william mobley

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...
October 4, 2016: Hippocampus
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
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
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
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
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
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
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
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
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
Michael R Ludwig, Kyoko Kojima, Gregory J Bowersock, Dongquan Chen, Nirag C Jhala, Donald J Buchsbaum, William E Grizzle, Christopher A Klug, James A Mobley
We have applied a serologic proteomic workflow involving three complementary MS approaches to a tissue-specific Kras(G12D) -knockin mouse model of pancreatic cancer that consistently forms precancerous lesions by 4 months of age. The three proteomics applications were highly complementary and allowed us to survey the entire range of low to high molecular weight serologic proteins. Combined, we identified 121 (49↓, 72↑) unique and statistically relevant serologic biomarkers with 88% previously reported to be associated with cancer and 38% specifically correlated with pancreatic cancer...
February 2016: Proteomics
Jong Wha Lee, Min Hyeon Shin, William Mobley, Adam R Urbach, Hugh I Kim
Mass spectrometry (MS)-based analysis using enzymatic digestion is widely used for protein sequencing and characterization. The large number of peptides generated from proteolysis, however, suppresses the signal of peptides with low ionization efficiency, thus precluding their observation and analysis. This study describes a technique for improved analysis of peptic peptides by adding the synthetic receptor cucurbit[7]uril (CB[7]), which binds selectively to peptides with N-terminal aromatic residues. Capturing the N-terminal phenylalanine (Phe) of peptides using CB[7] enhances the peptide abundances both in electrospray ionization MS and in matrix-assisted laser desorption ionization MS...
December 9, 2015: Journal of the American Chemical Society
Michael S Rafii, Hannah Wishnek, James B Brewer, Michael C Donohue, Seth Ness, William C Mobley, Paul S Aisen, Robert A Rissman
To gain further knowledge on the preclinical phase of Alzheimer's disease (AD), we sought to characterize cognitive performance, neuroimaging and plasma-based AD biomarkers in a cohort of non-demented adults with down syndrome (DS). The goal of the down syndrome biomarker Initiative (DSBI) pilot is to test feasibility of this approach for future multicenter studies. We enrolled 12 non-demented participants with DS between the ages of 30-60 years old. Participants underwent extensive cognitive testing, volumetric MRI, amyloid positron emission tomography (PET; 18F-florbetapir), fluorodeoxyglucose (FDG) PET (18F-fluorodeoxyglucose) and retinal amyloid imaging...
2015: Frontiers in Behavioral Neuroscience
Xiaoling Jiang, Chunhong Liu, Tao Yu, Li Zhang, Kai Meng, Zhuo Xing, Pavel V Belichenko, Alexander M Kleschevnikov, Annie Pao, Jennifer Peresie, Sarah Wie, William C Mobley, Y Eugene Yu
Down syndrome (DS), caused by trisomy 21, is the most common chromosomal disorder associated with developmental cognitive deficits. Despite intensive efforts, the genetic mechanisms underlying developmental cognitive deficits remain poorly understood, and no treatment has been proven effective. The previous mouse-based experiments suggest that the so-called Down syndrome critical region of human chromosome 21 is an important region for this phenotype, which is demarcated by Setd4/Cbr1 and Fam3b/Mx2. We first confirmed the importance of the Cbr1-Fam3b region using compound mutant mice, which carry a duplication spanning the entire human chromosome 21 orthologous region on mouse chromosome 16 [Dp(16)1Yey] and Ms1Rhr...
November 15, 2015: Human Molecular Genetics
Yingjun Zhao, I-Chu Tseng, Charles J Heyser, Edward Rockenstein, Michael Mante, Anthony Adame, Qiuyang Zheng, Timothy Huang, Xin Wang, Pharhad E Arslan, Paramita Chakrabarty, Chengbiao Wu, Guojun Bu, William C Mobley, Yun-Wu Zhang, Peter St George-Hyslop, Eliezer Masliah, Paul Fraser, Huaxi Xu
Progressive supranuclear palsy (PSP) is a movement disorder characterized by tau neuropathology where the underlying mechanism is unknown. An SNP (rs1768208 C/T) has been identified as a strong risk factor for PSP. Here, we identified a much higher T-allele occurrence and increased levels of the pro-apoptotic protein appoptosin in PSP patients. Elevations in appoptosin correlate with activated caspase-3 and caspase-cleaved tau levels. Appoptosin overexpression increased caspase-mediated tau cleavage, tau aggregation, and synaptic dysfunction, whereas appoptosin deficiency reduced tau cleavage and aggregation...
September 2, 2015: Neuron
Pavel V Belichenko, Alexander M Kleschevnikov, Ann Becker, Grant E Wagner, Larisa V Lysenko, Y Eugene Yu, William C Mobley
Down syndrome (DS), trisomy for chromosome 21, is the most common genetic cause of intellectual disability. The genomic regions on human chromosome 21 (HSA21) are syntenically conserved with regions on mouse chromosomes 10, 16, and 17 (Mmu10, Mmu16, and Mmu17). Recently, we created a genetic model of DS which carries engineered duplications of all three mouse syntenic regions homologous to HSA21. This 'triple trisomic' or TTS model thus represents the most complete and accurate murine model currently available for experimental studies of genotype-phenotype relationships in DS...
2015: PloS One
Marcelo R Malakooti, Mary E McBride, Bonnie Mobley, Joshua L Goldstein, Mark D Adler, William C McGaghie
BACKGROUND: Management of status epilepticus (SE) in the pediatric population is highly time-sensitive. Failure to follow a standard management algorithm may be due to ineffective provider education, and can lead to unfavorable outcomes. OBJECTIVE: To design a learning module using high-fidelity simulation technology to teach mastery achievement of a hospital algorithm for managing SE. METHODS: Thirty pediatrics interns were enrolled. Using the Angoff method, an expert panel developed the minimal passing score, which defined mastery...
June 2015: Journal of Graduate Medical Education
Aaron Selfridge, Nicholas Hyun, Chai-Chun Chiang, Sol M Reyna, April M Weissmiller, Linda Z Shi, Daryl Preece, William C Mobley, Michael W Berns
Axonal injury and stress have long been thought to play a pathogenic role in a variety of neurodegenerative diseases. However, a model for studying single-cell axonal injury in mammalian cells and the processes of repair has not been established. The purpose of this study was to examine the response of neuronal growth cones to laser-induced axonal damage in cultures of embryonic rat hippocampal neurons and induced pluripotent stem cell (iPSC) derived human neurons. A 532-nm pulsed [Formula: see text] picosecond laser was focused to a diffraction limited spot at a precise location on an axon using a laser energy/power that did not rupture the cell membrane (subaxotomy)...
January 2015: Neurophotonics
Anna B Cope, Kimberly A Powers, JoAnn D Kuruc, Peter A Leone, Jeffrey A Anderson, Li-Hua Ping, Laura P Kincer, Ronald Swanstrom, Victoria L Mobley, Evelyn Foust, Cynthia L Gay, Joseph J Eron, Myron S Cohen, William C Miller
OBJECTIVE: HIV transmission is influenced by status awareness and receipt of care and treatment. We analyzed these attributes of named partners of persons with acute HIV infection (index AHI cases) to characterize the transmission landscape in North Carolina (NC). DESIGN: Secondary analysis of programmatic data. METHODS: We used data from the NC Screening and Tracing of Active Transmission Program (2002-2013) to determine HIV status (uninfected, AHI, or chronic HIV infection [CHI]), diagnosis status (new or previously-diagnosed), and care and treatment status (not in care, in care and not on treatment, in care and on treatment) of index AHI cases' named partners...
2015: PloS One
Francesca L Facco, Corette B Parker, Uma M Reddy, Robert M Silver, Judette M Louis, Robert C Basner, Judith H Chung, Frank P Schubert, Grace W Pien, Susan Redline, Daniel R Mobley, Matthew A Koch, Hyagriv N Simhan, Chia-Ling Nhan-Chang, Samuel Parry, William A Grobman, David M Haas, Deborah A Wing, Brian M Mercer, George R Saade, Phyllis C Zee
OBJECTIVE: The objective of the Sleep Disordered Breathing substudy of the Nulliparous Pregnancy Outcomes Study Monitoring Mothers-to-be (nuMoM2b) is to determine whether sleep disordered breathing during pregnancy is a risk factor for adverse pregnancy outcomes. STUDY DESIGN: NuMoM2b is a prospective cohort study of 10,037 nulliparous women with singleton gestations that was conducted across 8 sites with a central Data Coordinating and Analysis Center. The Sleep Disordered Breathing substudy recruited 3702 women from the cohort to undergo objective, overnight in-home assessments of sleep disordered breathing...
April 2015: American Journal of Obstetrics and Gynecology
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