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https://www.readbyqxmd.com/read/28306513/tardigrades-use-intrinsically-disordered-proteins-to-survive-desiccation
#1
Thomas C Boothby, Hugo Tapia, Alexandra H Brozena, Samantha Piszkiewicz, Austin E Smith, Ilaria Giovannini, Lorena Rebecchi, Gary J Pielak, Doug Koshland, Bob Goldstein
Tardigrades are microscopic animals that survive a remarkable array of stresses, including desiccation. How tardigrades survive desiccation has remained a mystery for more than 250 years. Trehalose, a disaccharide essential for several organisms to survive drying, is detected at low levels or not at all in some tardigrade species, indicating that tardigrades possess potentially novel mechanisms for surviving desiccation. Here we show that tardigrade-specific intrinsically disordered proteins (TDPs) are essential for desiccation tolerance...
March 16, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28301502/long-term-moderate-wind-induced-sediment-resuspension-meeting-phosphorus-demand-of-phytoplankton-in-the-large-shallow-eutrophic-lake-taihu
#2
Jian-Ying Chao, Yi-Min Zhang, Ming Kong, Wei Zhuang, Long-Mian Wang, Ke-Qiang Shao, Guang Gao
The objective of this study was to investigate the impact of sediment resuspension and phosphorus (P) release on phytoplankton growth under different kinds of wind-wave disturbance conditions in the large and shallow eutrophic Lake Taihu in China. Short-term strong wind (STSW) conditions, long-term moderate wind (LTMW) conditions, and static/calm conditions were investigated. To address this objective, we (1) monitored changes in surface water P composition during field-based sediment resuspension caused by STSW conditions in Lake Taihu, and also conducted (2) a series of laboratory-based sediment resuspension experiments to simulate LTMW and calm conditions...
2017: PloS One
https://www.readbyqxmd.com/read/28301478/retrotransposon-activation-contributes-to-neurodegeneration-in-a-drosophila-tdp-43-model-of-als
#3
Lisa Krug, Nabanita Chatterjee, Rebeca Borges-Monroy, Stephen Hearn, Wen-Wei Liao, Kathleen Morrill, Lisa Prazak, Nikolay Rozhkov, Delphine Theodorou, Molly Hammell, Josh Dubnau
Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are two incurable neurodegenerative disorders that exist on a symptomological spectrum and share both genetic underpinnings and pathophysiological hallmarks. Functional abnormality of TAR DNA-binding protein 43 (TDP-43), an aggregation-prone RNA and DNA binding protein, is observed in the vast majority of both familial and sporadic ALS cases and in ~40% of FTLD cases, but the cascade of events leading to cell death are not understood...
March 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28286471/cytoplasmic-relocalization-of-tar-dna-binding-protein-43-is-not-sufficient-to-reproduce-cellular-pathologies-associated-with-als-in-vitro
#4
Heike J Wobst, Steven S Wesolowski, Jayashree Chadchankar, Louise Delsing, Steven Jacobsen, Jayanta Mukherjee, Tarek Z Deeb, John Dunlop, Nicholas J Brandon, Stephen J Moss
Mutations in the gene TARDBP, which encodes TAR DNA-binding protein 43 (TDP-43), are a rare cause of familial forms of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). While the majority of mutations are found in the C-terminal glycine-rich domain, an alanine to valine amino acid change at position 90 (A90V) in the bipartite nuclear localization signal (NLS) of TDP-43 has been described. This sequence variant has previously been shown to cause cytoplasmic mislocalization of TDP-43 and decrease protein solubility, leading to the formation of insoluble aggregates...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28286130/the-benefits-and-misfortunes-of-sds-in-top-down-proteomics
#5
Carolyn Kachuk, Alan A Doucette
Top-down proteomics (TDP) has great potential for high throughput proteoform characterization. With significant advances in mass spectrometry (MS) instrumentation permitting tandem MS of large intact proteins, a limitation to the widespread adoption of TDP still resides on front-end sample preparation protocols (e.g. fractionation, purification) that are amenable to MS analysis of intact proteins. Chromatographic strategies are improving but pose higher risk of sample loss. Gel-based separations (e.g. GELFrEE) may alleviate this concern but at the expense of requiring sodium dodecyl sulfate (SDS)...
March 8, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28282807/radiological-pathological-correlation-in-alzheimer-s-disease-systematic-review-of-antemortem-magnetic-resonance-imaging-findings
#6
Caroline Dallaire-Théroux, Brandy L Callahan, Olivier Potvin, Stephan Saikali, Simon Duchesne
BACKGROUND: The standard method of ascertaining Alzheimer's disease (AD) remains postmortem assessment of amyloid plaques and neurofibrillary degeneration. Vascular pathology, Lewy bodies, TDP-43, and hippocampal sclerosis are frequent comorbidities. There is therefore a need for biomarkers that can assess these etiologies and provide a diagnosis in vivo. OBJECTIVE: We conducted a systematic review of published radiological-pathological correlation studies to determine the relationship between antemortem magnetic resonance imaging (MRI) and neuropathological findings in AD...
March 6, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28282387/the-essential-and-downstream-common-proteins-of-amyotrophic-lateral-sclerosis-a-protein-protein-interaction-network-analysis
#7
Yimin Mao, Su-Wei Kuo, Le Chen, C J Heckman, M C Jiang
Amyotrophic Lateral Sclerosis (ALS) is a devastative neurodegenerative disease characterized by selective loss of motoneurons. While several breakthroughs have been made in identifying ALS genetic defects, the detailed molecular mechanisms are still unclear. These genetic defects involve in numerous biological processes, which converge to a common destiny: motoneuron degeneration. In addition, the common comorbid Frontotemporal Dementia (FTD) further complicates the investigation of ALS etiology. In this study, we aimed to explore the protein-protein interaction network built on known ALS-causative genes to identify essential proteins and common downstream proteins between classical ALS and ALS+FTD (classical ALS + ALS/FTD) groups...
2017: PloS One
https://www.readbyqxmd.com/read/28281308/overlapping-but-distinct-tdp-43-and-tau-pathologic-patterns-in-aged-hippocampi
#8
Vanessa D Smith, Adam D Bachstetter, Eseosa Ighodaro, Kelly Roberts, Erin L Abner, David W Fardo, Peter T Nelson
Intracellular proteinaceous aggregates (inclusion bodies) are almost always detectable at autopsy in brains of elderly individuals. Inclusion bodies composed of TDP-43 and tau proteins often coexist in the same brain, and each of these pathologic biomarkers is associated independently with cognitive impairment. However, uncertainties remain about how the presence and neuroanatomical distribution of inclusion bodies correlate with underlying diseases including Alzheimer's disease (AD). To address this knowledge gap, we analyzed data from the University of Kentucky AD Center autopsy series (n = 247); none of the brains had frontotemporal lobar degeneration...
March 9, 2017: Brain Pathology
https://www.readbyqxmd.com/read/28278534/transcription-and-splicing-factor-tdp-43-role-in-regulation-of-gene-expression-in-testis
#9
Prabhakara P Reddi
TDP-43 (TAR DNA binding Protein of 43 kD) is a transcription factor and RNA-binding protein with diverse functions. We cloned TDP-43 from the mouse testis in a screen for promoter-binding proteins and showed that it functions as a transcriptional repressor. TDP-43 plays a role in maintaining the precise pattern of spatiotemporal expression of the spermatid-specific Acrv1 gene during spermatogenesis by facilitating RNA polymerase II pausing at the promoter. We also showed that TDP-43 plays a partial role in preventing somatic cell expression of the Acrv1 gene by acting as an insulator-binding protein...
March 2017: Seminars in Reproductive Medicine
https://www.readbyqxmd.com/read/28275963/adverse-drug-event-causality-analysis-adeca-a-process-for-evaluating-evidence-and-assigning-drugs-to-risk-categories-for-sudden-death
#10
Raymond L Woosley, Klaus Romero, Craig W Heise, Tyler Gallo, Jared Tate, Raymond David Woosley, Sophie Ward
Growing evidence indicates that many drugs have the ability to cause a potentially lethal cardiac arrhythmia, torsades de pointes (TdP). This necessitates the development of a compilation of drugs that have this potential toxicity. Such a list is helpful in identifying the etiology of TdP in patients taking multiple drugs and assists decision making by those caring for patients at high risk of TdP. The Arizona Center for Education and Research on Therapeutics (AZCERT) has developed a process to standardize the identification of drugs and place them in risk categories for their clinical ability to cause TdP and QT prolongation...
March 8, 2017: Drug Safety: An International Journal of Medical Toxicology and Drug Experience
https://www.readbyqxmd.com/read/28274542/hypokalemia-in-women-and-methadone-therapy-are-the-strongest-non-cardiologic-factors-associated-with-qt-prolongation-in-an-emergency-department-setting
#11
Keith A Marill, Emily S Miller
BACKGROUND: Our primary objective was to determine the adjusted quantitative associations of clinical predictors with QT prolongation, a defining cause of Torsades de Pointes (TdP). METHODS: A retrospective cohort study was performed on consecutive emergency department patients identified by ECG acquisition date, and heart rate corrected QT (QTc) and QRS durations. QTc was modeled as a function of clinical predictors with multiple linear regression. RESULTS: 1010 patients were included...
February 10, 2017: Journal of Electrocardiology
https://www.readbyqxmd.com/read/28265061/amyotrophic-lateral-sclerosis-linked-mutations-increase-the-viscosity-of-liquid-like-tdp-43-rnp-granules-in-neurons
#12
Pallavi P Gopal, Jeffrey J Nirschl, Eva Klinman, Erika L F Holzbaur
Ribonucleoprotein (RNP) granules are enriched in specific RNAs and RNA-binding proteins (RBPs) and mediate critical cellular processes. Purified RBPs form liquid droplets in vitro through liquid-liquid phase separation and liquid-like non-membrane-bound structures in cells. Mutations in the human RBPs TAR-DNA binding protein 43 (TDP-43) and RNA-binding protein FUS cause amyotrophic lateral sclerosis (ALS), but the biophysical properties of these proteins have not yet been studied in neurons. Here, we show that TDP-43 RNP granules in axons of rodent primary cortical neurons display liquid-like properties, including fusion with rapid relaxation to circular shape, shear stress-induced deformation, and rapid fluorescence recovery after photobleaching...
March 6, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28257838/als-causing-cleavages-of-tdp-43-abolish-its-rrm2-structure-and-unlock-ctd-for-enhanced-aggregation-and-toxicity
#13
Yuanyuan Wei, Liangzhong Lim, Lu Wang, Jianxing Song
Pathological TDP-43 is cleaved into various fragments. Two major groups of ∼35 and ∼25 kDa have enhanced aggregation and cytotoxicity but the underlying mechanisms remain elusive. While the ∼35-kDa fragments contain entire RRM1, RRM2 and C-terminal domain (CTD) with a middle hydrophobic segment flanked by two prion-like regions; the ∼25-kDa one cleaved at Arg208 only consists of the truncated RRM2 and CTD. Remarkably, the 25-kDa fragment was characterized to induce cell death by gain of cytotoxicity and recapitulate pathological features of TDP-43 proteinopathies...
April 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28243725/motor-neuron-intrinsic-and-extrinsic-mechanisms-contribute-to-the-pathogenesis-of-fus-associated-amyotrophic-lateral-sclerosis
#14
Jelena Scekic-Zahirovic, Hajer El Oussini, Sina Mersmann, Kevin Drenner, Marina Wagner, Ying Sun, Kira Allmeroth, Stéphane Dieterlé, Jérôme Sinniger, Sylvie Dirrig-Grosch, Frédérique René, Dorothee Dormann, Christian Haass, Albert C Ludolph, Clotilde Lagier-Tourenne, Erik Storkebaum, Luc Dupuis
Motor neuron-extrinsic mechanisms have been shown to participate in the pathogenesis of ALS-SOD1, one familial form of amyotrophic lateral sclerosis (ALS). It remains unclear whether such mechanisms contribute to other familial forms, such as TDP-43 and FUS-associated ALS. Here, we characterize a single-copy mouse model of ALS-FUS that conditionally expresses a disease-relevant truncating FUS mutant from the endogenous murine Fus gene. We show that these mice, but not mice heterozygous for a Fus null allele, develop similar pathology as ALS-FUS patients and a mild motor neuron phenotype...
February 28, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28235538/perioperative-opioid-administration-in-children-with-and-without-developmental-delay-undergoing-outpatient-dental-surgery
#15
Erin R Conner, Erica D Musser, Kelsey M Colpitts, Dean L Laochamroonvorapongse, Jeffrey L Koh
STUDY OBJECTIVE: Prior research has indicated that children with developmental delay (DD) experience qualitative and quantitative differences in health care (Boulet et al., 2009). In the perioperative setting, there is concern that children with DD may be more likely to experience postoperative complications including agitation and nausea/vomiting than typically developing patients (TDP). Differences in the administration and dosage of perioperative opioids may contribute to this, however, empirical investigations are lacking...
February 2017: Journal of Clinical Anesthesia
https://www.readbyqxmd.com/read/28229125/the-clinical-neuroanatomical-and-neuropathologic-phenotype-of-tbk1-associated-frontotemporal-dementia-a-longitudinal-case-report
#16
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
#17
Anika R Bratt, Jacques C Finlay, Sarah E Hobbie, Benjamin D Janke, Adam C Worm, Kathrine L Kemmitt
Identification of nonpoint sources of nitrogen (N) and phosphorus (P) in urban systems is imperative to improving water quality and better managing 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 the winter export of N and P, we monitored stormwater 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%)...
March 21, 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
#18
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 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
#19
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
#20
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...
March 2017: Acta Neuropathologica
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