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https://www.readbyqxmd.com/read/28229125/the-clinical-neuroanatomical-and-neuropathologic-phenotype-of-tbk1-associated-frontotemporal-dementia-a-longitudinal-case-report
#1
Carolin A M Koriath, Martina Bocchetta, Emilie Brotherhood, Ione O C Woollacott, Penny Norsworthy, Javier Simón-Sánchez, Cornelis Blauwendraat, Katrina M Dick, Elizabeth Gordon, Sophie R Harding, Nick C Fox, Sebastian Crutch, Jason D Warren, Tamas Revesz, Tammaryn Lashley, Simon Mead, Jonathan D Rohrer
INTRODUCTION: Mutations in the TANK-binding kinase 1 (TBK1) gene have recently been shown to cause frontotemporal dementia (FTD). However, the phenotype of TBK1-associated FTD is currently unclear. METHODS: We performed a single case longitudinal study of a patient who was subsequently found to have a novel A705fs mutation in the TBK1 gene. He was assessed annually over a 7-year period with a series of clinical, cognitive, and magnetic resonance imaging assessments...
2017: Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
https://www.readbyqxmd.com/read/28215078/contribution-of-leaf-litter-to-nutrient-export-during-winter-months-in-an-urban-residential-watershed
#2
Anika Rose Bratt, Jacques C Finlay, Sarah E Hobbie, Benjamin D Janke, Adam C Worm, Kathrine L Kemmitt
Identification of non-point sources of nitrogen (N) and phosphorus (P) in urban systems is imperative to improve water quality and better manage eutrophication. Winter contributions and sources of annual N and P loads from urban watersheds are poorly characterized in northern cities because monitoring is often limited to warm weather periods. To determine winter export of N and P, we monitored storm water outflow in a residential watershed in Saint Paul, Minnesota during 2012-2014. Our data demonstrate that winter melt events contribute a high percentage of annual N and P export (50%)...
February 19, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/28213055/electrophysiological-measurements-that-can-explain-and-guide-temporary-accelerated-pacing-to-avert-re-occurrence-of-torsade-de-pointes-arrhythmias-in-the-canine-chronic-atrioventricular-block-model
#3
Sofieke C Wijers, Alexandre Bossu, Albert Dunnink, Jet D M Beekman, Rosanne Varkevisser, Alfonso Aranda Hernández, Mathias Meine, Marc A Vos
BACKGROUND: Pacing at higher rates is known to suppress Torsade de Pointes (TdP) arrhythmias. Nevertheless, exact application and mechanism need further clarification. In the anesthetized, canine, chronic atrioventricular block model, ventricular remodeling is responsible for a high and reproducible incidence of TdP upon a challenge with dofetilide. OBJECTIVE: We used this model to investigate by what mechanism accelerated pacing averts TdP and what repolarization parameter could be used to guide temporary applied accelerated pacing (TAP)...
February 14, 2017: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://www.readbyqxmd.com/read/28208729/altered-intracellular-milieu-of-adar2-deficient-motor-neurons-in-amyotrophic-lateral-sclerosis
#4
REVIEW
Takenari Yamashita, Megumi Akamatsu, Shin Kwak
Transactive response DNA-binding protein (TDP-43) pathology, and failure of A-to-I conversion (RNA editing) at the glutamine/arginine (Q/R) site of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor subunit GluA2, are etiology-linked molecular abnormalities that concomitantly occur in the motor neurons of most patients with amyotrophic lateral sclerosis (ALS). Adenosine deaminase acting on RNA 2 (ADAR2) specifically catalyzes GluA2 Q/R site-RNA editing. Furthermore, conditional ADAR2 knockout mice (AR2) exhibit a progressive ALS phenotype with TDP-43 pathology in the motor neurons, which is the most reliable pathological marker of ALS...
February 8, 2017: Genes
https://www.readbyqxmd.com/read/28205009/mixed-pathologies-including-chronic-traumatic-encephalopathy-account-for-dementia-in-retired-association-football-soccer-players
#5
Helen Ling, Huw R Morris, James W Neal, Andrew J Lees, John Hardy, Janice L Holton, Tamas Revesz, David D R Williams
In retired professional association football (soccer) players with a past history of repetitive head impacts, chronic traumatic encephalopathy (CTE) is a potential neurodegenerative cause of dementia and motor impairments. From 1980 to 2010, 14 retired footballers with dementia were followed up regularly until death. Their clinical data, playing career, and concussion history were prospectively collected. Next-of-kin provided consent for six to have post-mortem brain examination. Of the 14 male participants, 13 were professional and 1 was a committed amateur...
February 15, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28202194/study-of-factors-affecting-the-progression-and-termination-of-drug-induced-torsade-de-pointes-in-two-dimensional-cardiac-tissue
#6
Ponnuraj Kirthi Priya, M Ramasubba Reddy
INTRODUCTION: To study the conditions leading to the initiation and termination of drug induced Torsade de pointes (TdP) along with QT prolongation. METHODS: A 2D anisotropic transmural section of the ventricular myocardium is modeled using the TP06 equations and the cells are interconnected with gap junction conductances (GJC). The tissue is remodeled by reducing the repolarization reserve (by increasing calcium current (ICaL)) of all cells thus making them vulnerable to development of early after depolarizations (EADs)...
February 2, 2017: Journal of Electrocardiology
https://www.readbyqxmd.com/read/28197178/tdp-43-overexpression-impairs-presynaptic-integrity
#7
Lanier Heyburn, Charbel E-H Moussa
No abstract text is available yet for this article.
December 2016: Neural Regeneration Research
https://www.readbyqxmd.com/read/28188930/microrna-135a-regulates-sodium-calcium-exchanger-gene-expression-and-cardiac-electrical-activity
#8
Eric Duong, Jiening Xiao, Xiao Yan Qi, Stanley Nattel
BACKGROUND: Complete atrioventricular block (CAVB) causes arrhythmogenic remodeling and increases the risk of Torsades de Pointes (TdP) arrhythmias. MicroRNAs (miRNAs) are key regulators of gene-expression that contribute to cardiac remodeling. OBJECTIVE: To assess miRNA changes after complete atrioventricular block (CAVB) and identify novel candidates potentially involved in arrhythmogenic cardiac remodeling. METHODS: CAVB was induced in mice via His bundle ablation...
February 7, 2017: Heart Rhythm: the Official Journal of the Heart Rhythm Society
https://www.readbyqxmd.com/read/28186837/methadone-and-corrected-qt-prolongation-in-pain-and-palliative-care-patients-a-case-control-study
#9
Katherine M Juba, Tina M Khadem, David J Hutchinson, Jack E Brown
BACKGROUND: Methadone (ME) is commonly used in pain and palliative care (PPC) patients with refractory pain or intolerable opioid adverse effects (AEs). A unique ME AE is its corrected QT (QTc) interval prolongation risk, but most evidence exists in methadone maintenance therapy patients. OBJECTIVE: Our goal was to identify QTc interval prolongation risk factors in PPC patients receiving ME and other medications known to prolong the QTc interval and develop a risk stratification tool...
February 10, 2017: Journal of Palliative Medicine
https://www.readbyqxmd.com/read/28181891/-chronic-traumatic-encephalopathy-an-old-acquaintance-in-athletes
#10
E G B Vijverberg, A C M Pijnenburg, P Scheltens, Y A L Pijnenburg
- Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease caused by repetitive head injuries like those seen in sports such as boxing, American football and soccer.- The clinical features of CTE are a range of cognitive, psychiatric and motor symptoms, and histopathology involves deposits of hyperphosphorylated tau protein and the presence of TAR DNA-binding protein (TDP-43) with relatively little beta-amyloid.- CTE is difficult to differentiate clinically from Alzheimer's disease, frontotemporal dementia and psychiatric disorders because of the major symptom overlap between these conditions...
2017: Nederlands Tijdschrift Voor Geneeskunde
https://www.readbyqxmd.com/read/28181693/frontotemporal-lobar-degeneration-tdp-with-multiple-system-atrophy-phenocopy-syndrome
#11
Ana Luísa Sousa, Ricardo Taipa, Niall Quinn, Tamas Revesz, Manuel Melo Pires, Marina Magalhães
Multiple system atrophy (MSA) is a neurodegenerative disorder presenting with parkinsonism, cerebellar involvement, autonomic dysfunction and pyramidal signs (1). Two main clinical subtypes of MSA are recognized: a parkinsonian-type (MSA-P) associated with predominant nigrostriatal degeneration and a cerebellar-type (MSA-C) with predominant olivopontocerebellar atrophy. A 'definite' diagnosis requires pathological confirmation with demonstration of glial cytoplasmic inclusions comprising alpha-synuclein protein aggregates (1)...
February 9, 2017: Neuropathology and Applied Neurobiology
https://www.readbyqxmd.com/read/28176659/intrinsically-disordered-domains-amyloids-and-protein-liquid-phases-evolving-concepts-and-open-questions
#12
Miguel Ángel Mompeán, Douglas Vinson Laurents
Enzymes and structural proteins dominated thinking about protein structure and function for most of the twentieth century. In recent decades, however, we have begun to appreciate the significant physiological and pathological roles of nonglobular proteins. Amyloids first gained infamy from their implications in a score of human mortal diseases. However, they have recently been discovered to play vital physiological roles, such as memory consolidation in humans. This raises an important question: Can we inhibit pathological amyloids without affecting functional amyloids? Intrinsically disordered proteins (IDPs), many of which are prone to form amyloids, perform many essential functions, yet their importance has only been recognized in the last quarter century...
February 6, 2017: Protein and Peptide Letters
https://www.readbyqxmd.com/read/28172957/reduced-stress-granule-formation-and-cell-death-in-fibroblasts-with-the-a382t-mutation-of-tardbp-gene-evidence-for-loss-of-tdp-43-nuclear-function
#13
Sandro Orrù, Paola Coni, Andrea Floris, Roberto Littera, Carlo Carcassi, Valeria Sogos, Carla Brancia
No abstract text is available yet for this article.
October 15, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/28167899/cysteine-modifications-in-the-pathogenesis-of-als
#14
REVIEW
Cristiana Valle, Maria Teresa Carrì
Several proteins are found misfolded and aggregated in sporadic and genetic forms of amyotrophic lateral sclerosis (ALS). These include superoxide dismutase (SOD1), transactive response DNA-binding protein (TDP-43), fused in sarcoma/translocated in liposarcoma protein (FUS/TLS), p62, vasolin-containing protein (VCP), Ubiquilin-2 and dipeptide repeats produced by unconventional RAN-translation of the GGGGCC expansion in C9ORF72. Up to date, functional studies have not yet revealed a common mechanism for the formation of such diverse protein inclusions...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28167528/heat-shock-induced-phosphorylation-of-tar-dna-binding-protein-43-tdp-43-by-mapk-erk-kinase-regulates-tdp-43-function
#15
Wen Li, Ashley N Reeb, Binyan Lin, Praveen Subramanian, Erin E Fey, Catherine R Knoverek, Rachel L French, Eileen H Bigio, Yuna M Ayala
TAR DNA binding protein (TDP-43) is a highly conserved and essential DNA- and RNA-binding protein that controls gene expression through RNA processing, in particular, regulation of splicing. Intracellular aggregation of TDP-43 is a hallmark of amyotrophic lateral sclerosis and ubiquitin-positive frontotemporal lobar degeneration. This TDP-43 pathology is also present in other types of neurodegeneration including Alzheimer's disease. We report here that TDP-43 is a substrate of MEK, a central kinase in the MAPK/ERK signaling pathway...
February 6, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28163215/vegf-alleviates-als-csf-induced-cytoplasmic-accumulations-of-tdp-43-and-fus-tls-in-nsc-34-cells
#16
Shubham Shantanu, K Vijayalakshmi, S Shruthi, B K Chandrasekhar Sagar, T N Sathyaprabha, A Nalini, Trichur R Raju, Phalguni Anand Alladi
Cytoplasmic mislocalisation and aggregation of TDP-43 and FUS/TLS proteins in spinal motor neurons contribute to the pathogenesis of the highly fatal disorder amyotrophic lateral sclerosis (ALS). We investigated the neuroprotective effect of VEGF on expression of these proteins in the motor neuronal cell line NSC-34 modelled to reminisce sporadic form of ALS. We studied the expression of TDP-43 and FUS/TLS proteins after exposure to ALS-CSF and following VEGF supplementation by quantitative confocal microscopy and electron microscopy...
February 2, 2017: Journal of Chemical Neuroanatomy
https://www.readbyqxmd.com/read/28160067/tau-aggregation-influences-cognition-and-hippocampal-atrophy-in-the-absence-of-beta-amyloid-a-clinico-imaging-pathological-study-of-primary-age-related-tauopathy-part
#17
Keith A Josephs, Melissa E Murray, Nirubol Tosakulwong, Jennifer L Whitwell, David S Knopman, Mary M Machulda, Stephen D Weigand, Bradley F Boeve, Kejal Kantarci, Leonard Petrucelli, Val J Lowe, Clifford R Jack, Ronald C Petersen, Joseph E Parisi, Dennis W Dickson
We investigate whether there is any association between the Braak neurofibrillary tangle (NFT) stage and clinical and MRI features in definite primary age-related tauopathy (PART). We analysed 52 cases with a Braak NFT tangle stage >0 and ≤IV, and a Thal phase of 0 (no beta-amyloid present). Twenty-nine (56%) were female. Median age at death was 88 years (IQR 82-92 years). Fifteen (29%) were TDP-positive (75% TDP stage I), 16 (31%) had argyrophilic grain disease and three (6%) had alpha-synuclein-positive Lewy bodies...
February 3, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28158562/increased-cytoplasmic-tdp-43-reduces-global-protein-synthesis-by-interacting-with-rack1-on-polyribosomes
#18
Russo Arianna, Scardigli Raffaella, La Regina Federico, Murray E Melissa, Romano Nicla, Dickson W Dennis, Wolozin Benjamin, Cattaneo Antonino, Ceci Marcello
No abstract text is available yet for this article.
February 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28155653/novel-group-based-qsar-and-combinatorial-design-of-ck-1%C3%AE-inhibitors-as-neuroprotective-agents
#19
Kopal Joshi, Sukriti Goyal, Sonam Grover, Salma Jamal, Aditi Singh, Pawan Dhar, Abhinav Grover
BACKGROUND: Tar DNA binding protein 43 (TDP-43) hyperphosphorylation, caused by Casein kinase 1 (CK-1) protein isoforms, is associated with the onset and progression of Amyotrophic Lateral Sclerosis (ALS). Among the reported isoforms and splice variants of CK-1 protein superfamily, CK-1δ is known to phosphorylate different serine and threonine sites on TDP-43 protein in vitro and thus qualifies as a potential target for ALS treatment. RESULTS: The developed GQSAR (group based quantitative structure activity relationship) model displayed satisfactory statistical parameters for the dataset of experimentally reported N-Benzothiazolyl-2-Phenyl Acetamide derivatives...
December 22, 2016: BMC Bioinformatics
https://www.readbyqxmd.com/read/28153034/tdp-43-cryptic-exons-are-highly-variable-between-cell-types
#20
Yun Ha Jeong, Jonathan P Ling, Sophie Z Lin, Aneesh N Donde, Kerstin E Braunstein, Elisa Majounie, Bryan J Traynor, Katherine D LaClair, Thomas E Lloyd, Philip C Wong
BACKGROUND: TDP-43 proteinopathy is a prominent pathological feature that occurs in a number of human diseases including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and inclusion body myositis (IBM). Our recent finding that TDP-43 represses nonconserved cryptic exons led us to ask whether cell type-specific cryptic exons could exist to impact unique molecular pathways in brain or muscle. METHODS: In the present work, we investigated TDP-43's function in various mouse tissues to model disease pathogenesis...
February 2, 2017: Molecular Neurodegeneration
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