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https://www.readbyqxmd.com/read/28320656/targeting-effects-on-the-volume-of-the-focused-ultrasound-induced-blood-brain-barrier-opening-in-non-human-primates-in-vivo
#1
Maria Eleni Karakatsani, Gesthimani Samiotaki, Matthew Downs, Vincent Ferrera, Elisa Konofagou
Drug delivery to subcortical regions is susceptible to the blood-brain barrier (BBB) impeding the molecular exchange between the blood stream and the brain parenchyma. Focused ultrasound coupled with the administration of microbubbles has been proven to open the BBB locally, transiently and non-invasively both in rodents and in Non-Human-Primates (NHPs). The development of this disruption technique independent of MRI monitoring is of primordial importance yet restrained to the targeting optimization. The current paper establishes the linear relationship of the incidence angle with the volume of BBB opening (VBBB) and the Peak Negative Pressure (PNP) when sonicating the Caudate Nucleus and the Putamen region of five non-human-primates...
March 13, 2017: IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control
https://www.readbyqxmd.com/read/28298410/fus-inclusions-disrupt-rna-localization-by-sequestering-kinesin-1-and-inhibiting-microtubule-detyrosination
#2
Kyota Yasuda, Sarah F Clatterbuck-Soper, Meredith E Jackrel, James Shorter, Stavroula Mili
Cytoplasmic inclusions of the RNA-binding protein fused in sarcoma (FUS) represent one type of membraneless ribonucleoprotein compartment. Formation of FUS inclusions is promoted by amyotrophic lateral sclerosis (ALS)-linked mutations, but the cellular functions affected upon inclusion formation are poorly defined. In this study, we find that FUS inclusions lead to the mislocalization of specific RNAs from fibroblast cell protrusions and neuronal axons. This is mediated by recruitment of kinesin-1 mRNA and protein within FUS inclusions, leading to a loss of detyrosinated glutamate (Glu)-microtubules (MTs; Glu-MTs) and an inability to support the localization of RNAs at protrusions...
March 15, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28288521/young-onset-rapidly-progressive-als-associated-with-heterozygous-fus-mutation
#3
Marta Gromicho, Miguel Oliveira Santos, Anabela Pinto, Ana Pronto-Laborinho, Mamede De Carvalho
We report a 36-years-old Cape Verdean man who presented with respiratory insufficiency due to rapidly progressive sporadic amyotrophic lateral sclerosis (ALS), in whom FUS mutation c.1551C > G (p.Hist517Gln) in heterozygosity was identified, a finding previously described as non-pathogenic. The only previous report on this mutation was in a family from Cape Verde in which four members developed ALS; all were homozygous for the mutation. This case shows that this FUS mutation presents a highly variable penetrance and expressivity...
March 13, 2017: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration
https://www.readbyqxmd.com/read/28282387/the-essential-and-downstream-common-proteins-of-amyotrophic-lateral-sclerosis-a-protein-protein-interaction-network-analysis
#4
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/28282255/effect-of-zn-2-on-halohydrin-dehalogenase-expression-and-accumulation-through-multi-parameter-correlation-research-with-escherichia-coli-p84a-mc1061
#5
Xiao Li, Yu-Di Luo, Dong-Rui Pan, Xiao-Dan Shi, Ya-Li Tan, Zhi-Hong Li
Using 5 Zn(2+) supplementation strategies in a 50 L batch bioreactor named FUS-50L(A), possible correlations among Zn(2+) content and addition timing, physiologic activity (PA), halohydrin dehalogenase (HheC) accumulation of Escherichia coli P84A/MC1061 were systematically investigated. First, Zn(2+) was confirmed as the significant factor, and its optimal concentration for HheC expression was 3.87 mg/L through fermentation experiments in shaking flasks. Second, based on experimental results from the different strategies, it was found that PA, nutrient consumption rate (NCR) and specific growth rate (μ) for E...
March 10, 2017: Bioengineered
https://www.readbyqxmd.com/read/28281318/intracranial-myxoid-mesenchymal-tumors-with-ewsr1-creb-family-gene-fusions-myxoid-variant-of-angiomatoid-fibrous-histiocytoma-or-novel-entity
#6
Tejus A Bale, Angelica Oviedo, Harry Kozakewich, Caterina Giannini, Phani K Davineni, Keith Ligon, Sanda Alexandrescu
BACKGROUND: Intracranial myxoid mesenchymal tumor harboring EWSR1 fusions with CREB family of genes was recently described, and it resembles the myxoid variant of angiomatoid fibrous histiocytoma. We present 3 pediatric patients with intracranial EWSR1-rearranged myxoid mesenchymal neoplasm and provide a molecular genetic characterization of these tumors. METHODS: Clinical histories and imaging results were reviewed. Histology, immunohistochemistry, EWSR1, FUS, NR4A3 fluorescence in situ hybridization (FISH), and next generation sequencing (NGS) were performed...
March 9, 2017: Brain Pathology
https://www.readbyqxmd.com/read/28273913/als-linked-fus-exerts-a-gain-of-toxic-function-involving-aberrant-p38-mapk-activation
#7
Reddy Ranjith K Sama, Claudia Fallini, Rodolfo Gatto, Jeanne E McKeon, Yuyu Song, Melissa S Rotunno, Saul Penaranda, Izrail Abdurakhmanov, John E Landers, Gerardo Morfini, Scott T Brady, Daryl A Bosco
Mutations in Fused in Sarcoma/Translocated in Liposarcoma (FUS) cause familial forms of amyotrophic lateral sclerosis (ALS), a neurodegenerative disease characterized by progressive axonal degeneration mainly affecting motor neurons. Evidence from transgenic mouse models suggests mutant forms of FUS exert an unknown gain-of-toxic function in motor neurons, but mechanisms underlying this effect remain unknown. Towards this end, we studied the effect of wild type FUS (FUS WT) and three ALS-linked variants (G230C, R521G and R495X) on fast axonal transport (FAT), a cellular process critical for appropriate maintenance of axonal connectivity...
December 2017: Scientific Reports
https://www.readbyqxmd.com/read/28265061/amyotrophic-lateral-sclerosis-linked-mutations-increase-the-viscosity-of-liquid-like-tdp-43-rnp-granules-in-neurons
#8
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/28249774/primary-extraskeletal-myxoid-chondrosarcoma-of-bone-report-of-three-cases-and-review-of-the-literature
#9
L Finos, A Righi, T Frisoni, M Gambarotti, C Ghinelli, S Benini, D Vanel, P Picci
Extraskeletal myxoid chondrosarcoma is a rare neoplasm of soft tissue. The usual location is in deep parts of the proximal extremities and limb girdles in middle-aged adults. The bone location as primary location is extremely rare and few cases are reported. We present three cases arising in bone with molecular confirmation using both RT-PCR and FISH analysis. Patients include two men and one woman with an age of 62, 69 and 73 years old. The mean size of the lesion was 13cm (range 8-18cm). Tumors arose in the iliac bone in two cases and in the proximal humerus in the other case...
February 11, 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28244011/focused-ultrasound-an-emerging-therapeutic-modality-for-neurologic-disease
#10
Paul S Fishman, Victor Frenkel
Therapeutic ultrasound is only beginning to be applied to neurologic conditions, but the potential of this modality for a wide spectrum of brain applications is high. Engineering advances now allow sound waves to be targeted through the skull to a brain region selected with real time magnetic resonance imaging and thermography, using a commercial array of focused emitters. High intensities of sonic energy can create a coagulation lesion similar to that of older radiofrequency stereotactic methods, but without opening the skull...
February 27, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28243725/motor-neuron-intrinsic-and-extrinsic-mechanisms-contribute-to-the-pathogenesis-of-fus-associated-amyotrophic-lateral-sclerosis
#11
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/28241769/instrumented-gait-analysis-a-measure-of-gait-improvement-by-a-wheeled-walker-in-hospitalized-geriatric-patients
#12
Samuel Schülein, Jens Barth, Alexander Rampp, Roland Rupprecht, Björn M Eskofier, Jürgen Winkler, Karl-Günter Gaßmann, Jochen Klucken
BACKGROUND: In an increasing aging society, reduced mobility is one of the most important factors limiting activities of daily living and overall quality of life. The ability to walk independently contributes to the mobility, but is increasingly restricted by numerous diseases that impair gait and balance. The aim of this cross-sectional observation study was to examine whether spatio-temporal gait parameters derived from mobile instrumented gait analysis can be used to measure the gait stabilizing effects of a wheeled walker (WW) and whether these gait parameters may serve as surrogate marker in hospitalized patients with multifactorial gait and balance impairment...
February 27, 2017: Journal of Neuroengineering and Rehabilitation
https://www.readbyqxmd.com/read/28208797/multi-mycotoxin%C3%A2-analysis%C3%A2-in%C3%A2-durum%C3%A2-wheat%C3%A2-pasta%C3%A2-by%C3%A2-liquid%C3%A2-chromatography%C3%A2-coupled%C3%A2-to%C3%A2-quadrupole%C3%A2-orbitrap%C3%A2-mass%C3%A2-spectrometry
#13
Josefa Tolosa, Giulia Graziani, Anna Gaspari, Donato Chianese, Emilia Ferrer, Jordi Mañes, Alberto Ritieni
A simple and rapid multi-mycotoxin method for the determination of 17 mycotoxins  simultaneously  is  described  in  the  present  survey  on  durum  and  soft  wheat  pasta  samples.  Mycotoxins included in the study were those mainly reported in cereal samples: ochratoxin-A  (OTA), aflatoxin B1 (AFB1), zearalenone (ZON), deoxynivalenol (DON), 3-and 15-acetyl-deoxynivalenol  (3-AcDON and 15-AcDON), nivalenol (NIV), neosolaniol (NEO), fusarenon-X, (FUS-X), T-2 toxin  (T-2) and HT-2 toxin (HT-2), fumonisin B1 and B2 (FB1 and FB2), and four emerging mycotoxins:  three  enniatins  (ENA,  ENA1,  and  ENB),  and  beauvericin  (BEA)...
February 9, 2017: Toxins
https://www.readbyqxmd.com/read/28196303/the-long-noncoding-rna-schlah-suppresses-metastasis-of-hepatocellular-carcinoma-through-interacting-with-fus
#14
Zhouhong Ge, Zhuoan Cheng, Xinrong Yang, Xisong Huo, Ning Wang, Hui Wang, Cun Wang, Dishui Gu, Fangyu Zhao, Ming Yao, Jia Fan, Wenxin Qin
Emerging evidence has indicated that deregulation of long non-coding RNAs (lncRNAs) can contribute to the progression and metastasis of human cancer, including hepatocellular carcinoma (HCC). However, the roles of most lncRNAs in HCC remain largely unknown. Here we found a long noncoding RNA termed SchLAH (seven chromosome locus associated with HCC; also called BC035072) was generally downregulated in HCC. Low expression of SchLAH was significantly correlated with shorter overall survival of HCC patients. In vitro and in vivo assays indicated that overexpression of SchLAH inhibited the migration and lung metastasis of HCC cells...
February 14, 2017: Cancer Science
https://www.readbyqxmd.com/read/28176659/intrinsically-disordered-domains-amyloids-and-protein-liquid-phases-evolving-concepts-and-open-questions
#15
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/28167899/cysteine-modifications-in-the-pathogenesis-of-als
#16
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/28167348/3d-functional-ultrasound-imaging-of-the-cerebral-visual-system-in-rodents
#17
Marc Gesnik, Kevin Blaize, Thomas Deffieux, Jean-Luc Gennisson, José-Alain Sahel, Mathias Fink, Serge Picaud, Mickaël Tanter
3D functional imaging of the whole brain activity during visual task is a challenging task in rodents due to the complex tri-dimensional shape of involved brain regions and the fine spatial and temporal resolutions required to reveal the visual tract. By coupling functional ultrasound (fUS) imaging with a translational motorized stage and an episodic visual stimulation device, we managed to accurately map and to recover the activity of the visual cortices, the Superior Colliculus (SC) and the Lateral Geniculate Nuclei (LGN) in 3D...
February 3, 2017: NeuroImage
https://www.readbyqxmd.com/read/28164659/analysis-of-four-automated-urinalysis-systems-compared-to-reference-methods
#18
Kamila Bartosova, Zdenek Kubicek, Janka Franekova, Gustav Louzensky, Petra Lavrikova, Antonin Jabor
BACKGROUND: The aim of this study was to compare four automated urinalysis systems: the Iris iQ200 Sprint (Iris Diagnostics, U.S.A.) combined with the Arkray AUTION MAX AX 4030, Iris + AUTION, Arkray AU 4050 (Arkray Global Business, Inc., Japan), Dirui FUS 2000 (Dirui Industrial Co., P.R.C.), and Menarini sediMAX (Menarini, Italy). METHODS: Urine concentrations of protein and glucose (Iris, Dirui) were compared using reference quantitative analysis on an Abbott Architect c16000...
November 1, 2016: Clinical Laboratory
https://www.readbyqxmd.com/read/28163215/vegf-alleviates-als-csf-induced-cytoplasmic-accumulations-of-tdp-43-and-fus-tls-in-nsc-34-cells
#19
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/28161363/molecular-determinants-of-cytochrome-c-oxidase-iv-mrna-axonal-trafficking
#20
Amar N Kar, Jose Norberto S Vargas, Cai-Yun Chen, Jeffrey A Kowalak, Anthony E Gioio, Barry B Kaplan
In previous studies, we identified a putative 38-nucleotide stem-loop structure (zipcode) in the 3' untranslated region of the cytochrome c oxidase subunit IV (COXIV) mRNA that was necessary and sufficient for the axonal localization of the message in primary superior cervical ganglion (SCG) neurons. However, little is known about the proteins that interact with the COXIV-zipcode and regulate the axonal trafficking and local translation of the COXIV message. To identify proteins involved in the axonal transport of the COXIV mRNA, we used the biotinylated 38-nucleotide COXIV RNA zipcode as bait in the affinity purification of COXIV zipcode binding proteins...
February 1, 2017: Molecular and Cellular Neurosciences
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