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Yukie Kushimura, Takahiko Tokuda, Yumiko Azuma, Itaru Yamamoto, Ikuko Mizuta, Toshiki Mizuno, Masanori Nakagawa, Morio Ueyama, Yoshitaka Nagai, Hideki Yoshida, Masamitsu Yamaguchi
Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disease characterized by the motor neuron degeneration that eventually leads to complete paralysis and death within 2-5 years after disease onset. One of the major pathological hallmark of ALS is abnormal accumulation of inclusions containing TAR DNA-binding protein-43 (TDP-43). TDP-43 is normally found in the nucleus, but in ALS, it localizes in the cytoplasm as inclusions as well as in the nucleus. Loss of nuclear TDP-43 functions likely contributes to neurodegeneration...
2018: American Journal of Neurodegenerative Disease
Nada El Osta, Lana El Osta, Lydia Rabbaa Khabbaz, Robert Saad, Carole Abi-Ghosn, Martine Hennequin, Stephanie Tubert-Jeannin, Jihad Fakhouri
BACKGROUND AND OBJECTIVE: The percentage of Lebanese older people has increased considerably. Given that Lebanese seniors are marginalized in the health policy-making process, we suggest a high social inequality in oral health that has not been studied so far. The purpose of our study was to describe and compare oral health status in a group of Lebanese older people according to their socioeconomic status (SES) MATERIALS AND METHODS: Participants were recruited from three different primary health care clinics in Beirut, Lebanon...
March 8, 2018: Aging Clinical and Experimental Research
Wen-Yen Chai, Po-Chun Chu, Chih-Hung Tsai, Chung-Yin Lin, Hung-Wei Yang, Hsin-Yi Lai, Hao-Li Liu
Focused ultrasound (FUS) exposure with microbubbles can transiently open the blood-brain barrier (BBB) to deliver therapeutic molecules into CNS tissues. However, delivered molecular distribution/concentration at the target need to be controlled. Dynamic Contrast-Enhanced Magnetic-Resonance Imaging (DCE-MRI) is a well-established protocol for monitoring the pharmacokinetic/pharmacodynamic behavior of FUS-BBB opening. This study investigates the feasibility of using DCE-MRI to estimate molecular CNS penetration under various exposure conditions and molecule sizes...
March 7, 2018: Scientific Reports
Lieke H H Meeter, Everard G Vijverberg, Marta Del Campo, Annemieke J M Rozemuller, Laura Donker Kaat, Frank Jan de Jong, Wiesje M van der Flier, Charlotte E Teunissen, John C van Swieten, Yolande A L Pijnenburg
OBJECTIVE: To examine the clinical value of neurofilament light chain (NfL) and the phospho-tau/total tau ratio (p/t-tau) across the entire frontotemporal dementia (FTD) spectrum in a large, well-defined cohort. METHODS: CSF NfL and p/t-tau levels were studied in 361 patients with FTD: 179 behavioral variant FTD, 17 FTD with motor neuron disease (FTD-MND), 36 semantic variant primary progressive aphasia (PPA), 19 nonfluent variant PPA, 4 logopenic variant PPA (lvPPA), 42 corticobasal syndrome, and 64 progressive supranuclear palsy...
March 7, 2018: Neurology
Bin Yu, Xinguang Chen, Yan Wang
BACKGROUND: Marijuana and tobacco are considered two closely related substances. It is of great significance to understand the mutual impact of marijuana and cigarette use when more states in the US have legalized marijuana use. OBJECTIVE: This study aims to investigate the transitions between marijuana and cigarette use among adolescents and emerging adults. METHOD: Guided by the probabilistic discrete events systems (PDES) theory, a five-stage model with 21 transition paths was constructed to quantify dynamic transitions between marijuana and cigarette use...
March 7, 2018: American Journal of Drug and Alcohol Abuse
Kathryn Volkening, Brian Keller, Cheryl Leysta-Lantz, Michael J Strong
Tar DNA binding protein of 43kDa (TDP-43) is a dual function RNA/DNA binding protein with varied cellular functions. In degenerating motor neurons in ALS, TDP-43 relocalizes from the nucleus to the cytosol where it is sequestered into inclusions. It is likely that the pathogenic role of TDP-43 in ALS can involve either a gain or a loss of function, depending on the nature of its RNA or protein interactor. However, while TDP-43 binding partners have been identified in a range of model systems and from the human brain, interactors from human spinal cord tissue have not...
March 7, 2018: Journal of Proteome Research
Dianne Daniels, Shirley Sharabi, David Last, David Guez, Sharona Salomon, Zion Zivli, David Castel, Alex Volovick, Javier Grinfeld, Itay Rachmilevich, Talia Amar, Sigal Liraz-Zaltsman, Narek Sargsyan, Yael Mardor, Sagi Harnof
The goal of this study was to determine the feasibility of focused ultrasound-based neuromodulation affecting auditory evoked potentials (AEPs) in animals. Focused ultrasound-induced suppression of AEPs was performed in 22 rats and 5 pigs: Repetitive sounds were produced, and the induced AEPs were recorded before and repeatedly after FUS treatment of the auditory pathway. All treated animals exhibited a decrease in AEP amplitude post-treatment in contrast to animals undergoing the sham treatment. Suppression was weaker for rats treated at 2...
February 28, 2018: Ultrasound in Medicine & Biology
Tao Zhang, Yen-Ching Wu, Patrick Mullane, Yon Ju Ji, Honghe Liu, Lu He, Amit Arora, Ho-Yon Hwang, Amelia F Alessi, Amirhossein G Niaki, Goran Periz, Lin Guo, Hejia Wang, Elad Elkayam, Leemor Joshua-Tor, Sua Myong, John K Kim, James Shorter, Shao-En Ong, Anthony K L Leung, Jiou Wang
MicroRNA-mediated gene silencing is a fundamental mechanism in the regulation of gene expression. It remains unclear how the efficiency of RNA silencing could be influenced by RNA-binding proteins associated with the microRNA-induced silencing complex (miRISC). Here we report that fused in sarcoma (FUS), an RNA-binding protein linked to neurodegenerative diseases including amyotrophic lateral sclerosis (ALS), interacts with the core miRISC component AGO2 and is required for optimal microRNA-mediated gene silencing...
March 1, 2018: Molecular Cell
Dawn H W Lau, Naomi Hartopp, Natalie J Welsh, Sarah Mueller, Elizabeth B Glennon, Gábor M Mórotz, Ambra Annibali, Patricia Gomez-Suaga, Radu Stoica, Sebastien Paillusson, Christopher C J Miller
Fronto-temporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are two related and incurable neurodegenerative diseases. Features of these diseases include pathological protein inclusions in affected neurons with TAR DNA-binding protein 43 (TDP-43), dipeptide repeat proteins derived from the C9ORF72 gene, and fused in sarcoma (FUS) representing major constituent proteins in these inclusions. Mutations in C9ORF72 and the genes encoding TDP-43 and FUS cause familial forms of FTD/ALS which provides evidence to link the pathology and genetics of these diseases...
February 28, 2018: Cell Death & Disease
Zhe Qu, Santosh R D'Mello
A defining feature of neurodegenerative diseases is the abnormal and excessive loss of neurons. One molecule that is particularly important in promoting neuronal death in a variety of cell culture and in vivo models of neurodegeneration is histone deacetylase-3 (HDAC3), a member of the histone deacetylase family of proteins. As a step towards understanding how HDAC3 promotes neuronal death, we conducted a proteomic screen aimed at identifying proteins that were regulated by HDAC3. HDAC3 was overexpressed in cultured rat cerebellar granule neurons (CGNs) and protein lysates were analyzed by mass spectrometry...
January 1, 2018: Experimental Biology and Medicine
Yutao Zhang Master, Dan Wan Master, Fuping Gao Master
Low-grade fibromyxoid sarcoma (LGFMS) is a rare tumor with a bland histological appearance but malignant biological behavior. Primary LGFMS of breast has not been described in the English-language literature. Here, we report a 58-year-old Chinese female patient who presented with a painless mass in the right breast for more than 30 years. The tumor consists of spindle cells resembling fibroblasts and includes two kinds of morphological change, which are alternating collagenized hypocellular zone and cell-rich myxoid area...
February 24, 2018: Human Pathology
K Specht, W Hartmann
Sarcomas of the Ewing family of tumors are aggressive neoplasms occurring in bone and soft tissue of mostly children and young adults. Classical Ewing sarcomas are pathognomonically characterized by fusions between a gene of the RNA-binding TET family (EWSR1 or FUS) with a gene of the ETS-transcription family (FLI1, ERG, ETV1, ETV4 or FEV). Less frequent cases designated as Ewing-like sarcomas show different genetic rearrangements between EWSR1 and non-ETS genes (NFATC2, POU5F1, SMARCA5, PATZ, ZSG, SP3). Moreover, new molecular alterations biologically unrelated to Ewing sarcomas have recently been described in the category of undifferentiated round cell sarcomas including CIC-DUX4 fusions or BCOR alterations, each carrying unique gene expression signatures...
February 26, 2018: Der Pathologe
Rodger J Elble, Ludy Shih, Jeffrey W Cozzens
Essential tremor is the most common form of pathologic tremor. Surgical therapies disrupt tremorogenic oscillation in the cerebellothalamocortical pathway and are capable of abolishing severe tremor that is refractory to available pharmacotherapies. Surgical methods are rapidly improving and are the subject of this review. Areas covered: A PubMed search on January 18, 2018 using the query essential tremor AND surgery produced 839 abstracts. 379 papers were selected for review of the methods, efficacy, safety and expense of stereotactic deep brain stimulation (DBS), stereotactic radiosurgery (SRS), focused ultrasound (FUS) ablation, and radiofrequency ablation of the cerebellothalamocortical pathway...
February 23, 2018: Expert Review of Neurotherapeutics
Susanne Wegmann, Bahareh Eftekharzadeh, Katharina Tepper, Katarzyna M Zoltowska, Rachel E Bennett, Simon Dujardin, Pawel R Laskowski, Danny MacKenzie, Tarun Kamath, Caitlin Commins, Charles Vanderburg, Allyson D Roe, Zhanyun Fan, Amandine M Molliex, Amayra Hernandez-Vega, Daniel Muller, Anthony A Hyman, Eckhard Mandelkow, J Paul Taylor, Bradley T Hyman
The transition between soluble intrinsically disordered tau protein and aggregated tau in neurofibrillary tangles in Alzheimer's disease is unknown. Here, we propose that soluble tau species can undergo liquid-liquid phase separation (LLPS) under cellular conditions and that phase-separated tau droplets can serve as an intermediate toward tau aggregate formation. We demonstrate that phosphorylated or mutant aggregation prone recombinant tau undergoes LLPS, as does high molecular weight soluble phospho-tau isolated from human Alzheimer brain...
February 22, 2018: EMBO Journal
Maria A Bobes, Agustin Lage-Castellanos, Ela I Olivares, Jhoanna Perez Hidalgo-Gato, Jaime Iglesias, Ana Maria Castro-Laguardia, Pedro Valdes-Sosa
Event related potentials (ERPs) provide precise temporal information about cognitive processing, but with poor spatial resolution, while functional magnetic resonance imaging (fMRI) reliably identifies brain areas involved, but with poor temporal resolution. Here we use fMRI to guide source localization of the ERPs at different times for studying the temporal dynamics of the neural system for recognizing familiar faces. fMRI activation areas were defined in a previous experiment applying the same paradigm used for ERPs...
February 20, 2018: Brain Topography
José Manuel Matamala, Raul Arias-Carrasco, Carolina Sanchez, Markus Uhrig, Leslie Bargsted, Soledad Matus, Vinicius Maracaja-Coutinho, Sebastian Abarzua, Brigitte van Zundert, Renato Verdugo, Patricio Manque, Claudio Hetz
The occurrence of mutations of TDP-43, FUS, and C9ORF72 in amyotrophic lateral sclerosis (ALS) suggests pathogenic alterations to RNA metabolism and specifically to microRNA (miRNA) biology. Moreover, several ALS-related proteins impact stress granule dynamics affecting miRNA biogenesis and cellular miRNA levels. miRNAs are present in different biological fluids and have been proposed as potential biomarkers. Here we used next-generation sequencing to perform a comparative analysis of the expression profile of circulating miRNAs in the serum of 2 mutant superoxide dismutase 1 transgenic mice...
April 2018: Neurobiology of Aging
V S Tompkins, D P Valverde, W N Moss
OBJECTIVE: The function of Epstein-Barr virus (EBV) stable intronic sequence (sis)RNAs, non-coding RNAs transcribed from a region required for EBV-mediated cellular transformation, remain unknown. To better understand the function of ebv-sisRNA-1 and ebv-sisRNA-2 from the internal repeat (IR)1 region of EBV, we used a combination of bioinformatics and biochemistry to identify associated RNA binding proteins. The findings reported here are part of ongoing studies to determine the functions of non-coding RNAs from the IR1 region of EBV...
February 20, 2018: BMC Research Notes
Sara C Cunha, S Sá, José O Fernandes
Nuts consumption plays an important role in Mediterranean diet, being a good source of proteins, vitamins, minerals and unsaturated fatty acids. However, nuts can be also a source of harmful mycotoxins with negative impact on human health. In this work, the occurrence of 16 mycotoxins belonging to different chemical classes, was assessed in several nut products. The analytical method used was based on modified QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe) procedure followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis...
February 16, 2018: Food and Chemical Toxicology
Mark T Burgess, Iason Zacharias Apostolakis, Elisa E Konofagou
Image-guided monitoring of microbubble-based focused ultrasound (FUS) therapies relies on the accurate localization of FUS-stimulated microbubble activity (i.e. acoustic cavitation). Passive cavitation imaging with ultrasound arrays can achieve this, but with insufficient spatial resolution. In this study, we address this limitation and perform high-resolution monitoring of acoustic cavitation-mediated blood-brain barrier (BBB) opening with a new technique called power cavitation imaging. By synchronizing the FUS transmit and passive receive acquisition, high-resolution passive cavitation imaging was achieved by using delay and sum (DAS) beamforming with absolute time delays...
February 19, 2018: Physics in Medicine and Biology
Silvia Biscarini, Davide Capauto, Giovanna Peruzzi, Lei Lu, Alessio Colantoni, Tiziana Santini, Neil A Shneider, Elisa Caffarelli, Pietro Laneve, Irene Bozzoni
Long non-coding RNAs (lncRNAs) are currently recognized as crucial players in nervous system development, function and pathology. In Amyotrophic Lateral Sclerosis (ALS), identification of causative mutations in FUS and TDP-43 or hexanucleotide repeat expansion in C9ORF72 point to the essential role of aberrant RNA metabolism in neurodegeneration. In this study, by taking advantage of an in vitro differentiation system generating mouse motor neurons (MNs) from embryonic stem cells, we identified and characterized the long non-coding transcriptome of MNs...
January 31, 2018: Stem Cell Research
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