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https://www.readbyqxmd.com/read/28942918/structure-of-fus-protein-fibrils-and-its-relevance-to-self-assembly-and-phase-separation-of-low-complexity-domains
#1
Dylan T Murray, Masato Kato, Yi Lin, Kent R Thurber, Ivan Hung, Steven L McKnight, Robert Tycko
Polymerization and phase separation of proteins containing low-complexity (LC) domains are important factors in gene expression, mRNA processing and trafficking, and localization of translation. We have used solid-state nuclear magnetic resonance methods to characterize the molecular structure of self-assembling fibrils formed by the LC domain of the fused in sarcoma (FUS) RNA-binding protein. From the 214-residue LC domain of FUS (FUS-LC), a segment of only 57 residues forms the fibril core, while other segments remain dynamically disordered...
September 16, 2017: Cell
https://www.readbyqxmd.com/read/28941924/risk-stratification-of-equivocal-pi-rads-lesions-in-mp-mri-of-the-prostate
#2
T Ullrich, M Quentin, C Arsov, A K Schmaltz, A Tschischka, N Laqua, A Hiester, D Blondin, R Rabenalt, P Albers, G Antoch, L Schimmöller
PURPOSE: To systematically analyze patients with PI-RADS-3-lesions (called 'equivocal' according to PI-RADS v2) in multiparametric prostate MRI (mp-MRI) and MR-targeted plus systematic transrectal ultrasound-guided (TRUS-GB) biopsies as reference standard. MATERIAL AND METHODS: One hundred and twenty consecutive patients with a PI-RADS overall score of 3 after mp-MRI (T2WI, DWI, DCE-MRI) at 3T and subsequent targeted MRI/US fusion-guided (FUS-GB) plus systematic 12-core TRUS-GB were retrospectively included in this study...
September 20, 2017: Journal of Urology
https://www.readbyqxmd.com/read/28941811/reversible-induction-of-tdp-43-granules-in-cortical-neurons-after-traumatic-injury
#3
Diana Wiesner, Lilla Tar, Birgit Linkus, Akila Chandrasekar, Florian Olde Heuvel, Luc Dupuis, William Tsao, Philip C Wong, Albert Ludolph, Francesco Roselli
Traumatic brain injury (TBI) has been proposed as a risk factor for neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). To determine whether TBI might trigger or exacerbate ALS-relevant pathology, we delivered a mild stab-wound injury to the motor cortex of three different ALS mouse models expressing mutations in SOD1, TDP-43 or FUS and scrutinized the effects on the formation of phospho-TDP-43 (pTDP-43) cytoplasmic granules. Stab-injury induced the formation of cytoplasmic TDP-43 granules in wt animals, peaking at 3dpi; a much larger response was seen in mutant TDP-43 mice, whose response peaked at 7dpi...
September 20, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28939748/in-depth-genetic-analysis-of-sclerosing-epithelioid-fibrosarcoma-reveals-recurrent-genomic-alterations-and-potential-treatment-targets
#4
Elsa Arbajian, Florian Puls, Cristina R Antonescu, M Fernanda Amary, Raf Sciot, Maria Debiec-Rychter, Vaiyapuri Sumathi, Marcus Järås, Linda Magnusson, Jenny Nilsson, Jakob Hofvander, Fredrik Mertens
PURPOSE: Sclerosing epithelioid fibrosarcoma (SEF) is a highly aggressive soft tissue sarcoma closely related to low-grade fibromyxoid sarcoma (LGFMS). Some tumors display morphological characteristics of both SEF and LGFMS, so called hybrid SEF/LGFMS. Despite the overlap of gene fusion variants between these two tumor types, SEF is much more aggressive. The present study aimed to further characterize SEF and hybrid SEF/LGFMS genetically in order to better understand the role of the characteristic fusion genes and possible additional genetic alterations in tumorigenesis...
September 22, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28933214/magnetic-enhancement-of-stem-cell-targeted-delivery-into-the-brain-following-mr-guided-focused-ultrasound-for-opening-the-blood-brain-barrier
#5
Wei-Bin Shen, Pavlos Anastasiadis, Ben Nguyen, Deborah Yarnell, Paul J Yarowsky, Victor Frenkel, Paul S Fishman
Focused ultrasound (FUS)-mediated blood-brain barrier disruption (BBBD) can enable even large therapeutics such as stem cells to enter the brain from the bloodstream. However, the efficiency is relatively low. Our previous study showed that human neural progenitor cells (hNPCs) loaded with superparamagnetic iron oxide nanoparticles (SPIONs) in culture were attracted by an external magnetic field. In vivo, enhanced brain retention was observed near a magnet mounted on the skull in a rat model of traumatic brain injury, where BBBD also occurs...
July 2017: Cell Transplantation
https://www.readbyqxmd.com/read/28928015/dendritic-homeostasis-disruption-in-a-novel-frontotemporal-dementia-mouse-model-expressing-cytoplasmic-fused-in-sarcoma
#6
Gen Shiihashi, Daisuke Ito, Itaru Arai, Yuki Kobayashi, Kanehiro Hayashi, Shintaro Otsuka, Kazunori Nakajima, Michisuke Yuzaki, Shigeyoshi Itohara, Norihiro Suzuki
Cytoplasmic aggregation of fused in sarcoma (FUS) is detected in brain regions affected by amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), which compose the disease spectrum, FUS proteinopathy. To understand the pathomechanism of ALS-FTD-associated FUS, we examined the behavior and cellular properties of an ALS mouse model overexpressing FUS with nuclear localization signal deletion. Mutant FUS transgenic mice showed hyperactivity, social interactional deficits, and impaired fear memory retrieval, all of which are compatible with FTD phenotypes...
September 9, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28924037/intrinsically-disordered-sequences-enable-modulation-of-protein-phase-separation-through-distributed-tyrosine-motifs
#7
Yuan Lin, Simon L Currie, Michael Keith Rosen
Liquid-liquid phase separation (LLPS) is thought to contribute to establishment of many biomolecular condensates, eukaryotic cell structures that concentrate diverse macromolecules but lack a bounding membrane. RNA granules control RNA metabolism and comprise a large class of condensates that are enriched in RNA-binding proteins and RNA molecules. Many RNA granule proteins are composed of both modular domains and intrinsically disordered regions (IDRs) having low amino acid sequence complexity. Phase separation of these molecules likely plays an important role in the generation and stability of RNA granules...
September 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28923025/intrafamilial-phenotypic-heterogeneity-in-a-taiwanese-family-with-a-mapt-p-r5h-mutation-a-case-report-and-literature-review
#8
Hui-Chi Lin, Chin-Hsien Lin, Pei-Lung Chen, Shih-Jung Cheng, Pei-Hao Chen
BACKGROUND: Frontotemporal degeneration (FTD) is a clinically and genetically heterogeneous neurodegenerative disorder characterized by deficits in executive function that frequently overlaps with parkinsonism and motor neuron disorders. Several genes have been identified to cause autosomal dominant forms of FTD, including the gene coding for the protein associated with microtubule tau (MAPT). While most reported pathogenic mutations in MAPT occur in exons 9-13, few families have been reported with mutations outside of this region...
September 18, 2017: BMC Neurology
https://www.readbyqxmd.com/read/28917284/neurosurgical-applications-of-high-intensity-focused-ultrasound-with-magnetic-resonance-thermometry
#9
REVIEW
Rivka R Colen, Iman Sahnoune, Jeffrey S Weinberg
Magnetic resonance guided focused ultrasound surgery (MRgFUS) has potential noninvasive effects on targeted tissue. MRgFUS integrates MRI and focused ultrasound surgery (FUS) into a single platform. MRI enables visualization of the target tissue and monitors ultrasound-induced effects in near real-time during FUS treatment. MRgFUS may serve as an adjunct or replace invasive surgery and radiotherapy for specific conditions. Its thermal effects ablate tumors in locations involved in movement disorders and essential tremors...
October 2017: Neurosurgery Clinics of North America
https://www.readbyqxmd.com/read/28913355/evaluation-of-mechanical-properties-and-marginal-fit-of-crowns-fabricated-using-commercially-pure-titanium-and-fus-invest
#10
Jinshuang Wu, Xianli Wang, Helin Xing, Tianwen Guo, Chaofang Dong, Sefei Yang
This study investigated the mechanical properties and single crown accuracy of the tailor-made Fourth University Stomatology investment (FUS-invest) for casting titanium. Background. Current investment for casting titanium is not optimal for obtaining high-quality castings, and the commercially available titanium investment is costly. Methods. Titanium specimens were cast using the tailor-made FUS-invest. The mechanical properties were tested using a universal testing machine. Fractured castings were characterized by energy-dispersive spectroscopy...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28912896/investigation-of-the-safety-of-focused-ultrasound-induced-blood-brain-barrier-opening-in-a-natural-canine-model-of-aging
#11
Meaghan Anne O'Reilly, Ryan Matthew Jones, Edward Barrett, Anthony Schwab, Elizabeth Head, Kullervo Hynynen
Rationale: Ultrasound-mediated opening of the Blood-Brain Barrier(BBB) has shown exciting potential for the treatment of Alzheimer's disease(AD). Studies in transgenic mouse models have shown that this approach can reduce plaque pathology and improve spatial memory. Before clinical translation can occur the safety of the method needs to be tested in a larger brain that allows lower frequencies be used to treat larger tissue volumes, simulating clinical situations. Here we investigate the safety of opening the BBB in half of the brain in a large aged animal model with naturally occurring amyloid deposits...
2017: Theranostics
https://www.readbyqxmd.com/read/28912567/structural-and-dynamical-characteristics-of-flow-units-in-metallic-glasses
#12
S T Liu, F X Li, M Z Li, W H Wang
The metallic glasses (MGs) are conjectured to be heterogeneous-their microscopic structures are embedded with localized, soft and loosely packed atomic regions, which are termed as flow units (FUs). Detailed knowledges on the structure and dynamical features of FUs are essential for understanding the plasticity of MGs. In our study, by performing dynamical tests on MGs in molecular dynamics simulations, we show that mechanical hysteretic loops are formed in the strain-stress curves due to the undergoing plastic events...
September 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28903344/establishing-a-patient-derived-xenograft-model-of-human-myxoid-and-round-cell-liposarcoma
#13
Yiming Qi, Yu Hu, Hua Yang, Rongyuan Zhuang, Yingyong Hou, Hanxing Tong, Yi Feng, Yuan Huang, Quan Jiang, Qunsheng Ji, Qingyang Gu, Zhixiang Zhang, Xuzhen Tang, Weiqi Lu, Yuhong Zhou
Myxoid and round cell liposarcoma (MRCL) is a common type of soft tissue sarcoma. The lack of patient-derived tumor xenograft models that are highly consistent with human tumors has limited the drug experiments for this disease. Hence, we aimed to develop and validate a patient-derived tumor xenograft model of MRCL. A tumor sample from a patient with MRCL was implanted subcutaneously in an immunodeficient mouse shortly after resection to establish a patient-derived tumor xenograft model. After the tumor grew, it was resected and divided into several pieces for re-implantation and tumor passage...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28871027/case-management-in-primary-care-among-frequent-users-of-healthcare-services-with-chronic-conditions-protocol-of-a-realist-synthesis
#14
Catherine Hudon, Maud-Christine Chouinard, Kris Aubrey-Bassler, Nazeem Muhajarine, Fred Burge, Pierre Pluye, Paula L Bush, Vivian R Ramsden, France Legare, Line Guenette, Paul Morin, Mireille Lambert, Antoine Groulx, Martine Couture, Cameron Campbell, Margaret Baker, Lynn Edwards, Véronique Sabourin, Claude Spence, Gilles Gauthier, Mike Warren, Julie Godbout, Breanna Davis, Norma Rabbitskin
INTRODUCTION: A common reason for frequent use of healthcare services is the complex healthcare needs of individuals suffering from multiple chronic conditions, especially in combination with mental health comorbidities and/or social vulnerability. Frequent users (FUs) of healthcare services are more at risk for disability, loss of quality of life and mortality. Case management (CM) is a promising intervention to improve care integration for FU and to reduce healthcare costs. This review aims to develop a middle-range theory explaining how CM in primary care improves outcomes among FU with chronic conditions, for what types of FU and in what circumstances...
September 3, 2017: BMJ Open
https://www.readbyqxmd.com/read/28860970/failure-to-deliver-and-translate-new-insights-into-rna-dysregulation-in-als
#15
REVIEW
Alyssa N Coyne, Benjamin L Zaepfel, Daniela C Zarnescu
Amyotrophic Lateral Sclerosis (ALS) is a progressive and fatal neurodegenerative disease affecting both upper and lower motor neurons. The molecular mechanisms underlying disease pathogenesis remain largely unknown. Multiple genetic loci including genes involved in proteostasis and ribostasis have been linked to ALS providing key insights into the molecular mechanisms underlying disease. In particular, the identification of the RNA binding proteins TDP-43 and fused in sarcoma (FUS) as causative factors of ALS resulted in a paradigm shift centered on the study of RNA dysregulation as a major mechanism of disease...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28859526/increase-in-dna-methylation-in-patients-with-amyotrophic-lateral-sclerosis-carriers-of-not-fully-penetrant-sod1-mutations
#16
Fabio Coppedè, Andrea Stoccoro, Lorena Mosca, Roberta Gallo, Claudia Tarlarini, Christian Lunetta, Alessandro Marocchi, Lucia Migliore, Silvana Penco
OBJECTIVE: More than 180 different superoxide dismutase 1 (SOD1) mutations have been described to date in amyotrophic lateral sclerosis (ALS) patients, including not completely penetrant ones leading to phenotypic heterogeneity among carriers. We collected DNA samples from five ALS families with not fully penetrant SOD1 mutations (p.Asn65Ser, p.Gly72Ser, p.Gly93Asp, and p.Gly130_Glu133del) searching for epigenetic differences among ALS patients, asymptomatic/paucisymptomatic carriers and non-carrier family members...
September 1, 2017: Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration
https://www.readbyqxmd.com/read/28848385/translational-identification-of-transcriptional-signatures-of-major-depression-and-antidepressant-response
#17
Mylène Hervé, Aurélie Bergon, Anne-Marie Le Guisquet, Samuel Leman, Julia-Lou Consoloni, Nicolas Fernandez-Nunez, Marie-Noëlle Lefebvre, Wissam El-Hage, Raoul Belzeaux, Catherine Belzung, El Chérif Ibrahim
Major depressive disorder (MDD) is a highly prevalent mental illness whose therapy management remains uncertain, with more than 20% of patients who do not achieve response to antidepressants. Therefore, identification of reliable biomarkers to predict response to treatment will greatly improve MDD patient medical care. Due to the inaccessibility and lack of brain tissues from living MDD patients to study depression, researches using animal models have been useful in improving sensitivity and specificity of identifying biomarkers...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28848341/enhanced-delivery-of-paclitaxel-liposomes-using-focused-ultrasound-with-microbubbles-for-treating-nude-mice-bearing-intracranial-glioblastoma-xenografts
#18
Yuanyuan Shen, Zhaoke Pi, Fei Yan, Chih-Kuang Yeh, Xiaojun Zeng, Xianfen Diao, Yaxin Hu, Siping Chen, Xin Chen, Hairong Zheng
Paclitaxel liposomes (PTX-LIPO) are a clinically promising antineoplastic drug formulation for the treatment of various extracranial cancers, excluding glioblastoma. A main reason for this is the presence of the blood-brain barrier (BBB) or blood-tumor barrier (BTB), preventing liposomal drugs from crossing at a therapeutically meaningful level. Focused ultrasound (FUS) in conjunction with microbubbles (MBs) has been suggested in many studies to be an effective approach to increase the BBB or BTB permeability...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28842245/silencing-of-fus-in-the-common-marmoset-callithrix-jacchus-brain-via-stereotaxic-injection-of-an-adeno-associated-virus-encoding-shrna
#19
Kuniyuki Endo, Shinsuke Ishigaki, Yoshito Masamizu, Yusuke Fujioka, Akiya Watakabe, Tetsuo Yamamori, Nobuhiko Hatanaka, Atsushi Nambu, Haruo Okado, Masahisa Katsuno, Hirohisa Watanabe, Masanori Matsuzaki, Gen Sobue
Fused in sarcoma (FUS) is an RNA binding protein that is involved in frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). To establish the common marmoset (Callithrix jacchus) as a model for FTLD, we generated a stereotaxic injection-based marmoset model of FUS-silencing. We designed shRNAs against the marmoset FUS gene and generated an AAV9 virus encoding the most effective shRNA against FUS (shFUS). The AAV encoding shFUS (AAV-shFUS) was introduced into the frontal cortex of young adult marmosets, whereas AAV encoding a control shRNA was injected into the contralateral side...
August 24, 2017: Neuroscience Research
https://www.readbyqxmd.com/read/28819458/focused-ultrasound-hyperthermia-mediated-drug-delivery-using-thermosensitive-liposomes-and-visualized-with-in-vivo-two-photon-microscopy
#20
Marc A Santos, David E Goertz, Kullervo Hynynen
The future of nanomedicines in oncology requires leveraging more than just the passive drug accumulation in tumors through the enhanced permeability and retention effect. Promising results combining mild hyperthermia (HT) with lyso-thermosensitive liposomal doxorubicin (LTSL-DOX) has led to improved drug delivery and potent antitumor effects in pre-clinical studies. The ultimate patient benefit from these treatments can only be realized when robust methods of HT can be achieved clinically. One of the most promising methods of non-invasive HT is the use of focused ultrasound (FUS) with MRI thermometry for anatomical targeting and feedback...
2017: Theranostics
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