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https://www.readbyqxmd.com/read/29789605/neuromodulation-of-sensory-networks-in-monkey-brain-by-focused-ultrasound-with-mri-guidance-and-detection
#1
Pai-Feng Yang, M Anthony Phipps, Allen T Newton, Vandiver Chaplin, John C Gore, Charles F Caskey, Li Min Chen
Focused ultrasound (FUS) has gained recognition as a technique for non-invasive neuromodulation with high spatial precision and the ability to both excite and inhibit neural activity. Here we demonstrate that MRI-guided FUS is capable of exciting precise targets within areas 3a/3b in the monkey brain, causing downstream activations in off-target somatosensory and associated brain regions which are simultaneously detected by functional MRI. The similarity between natural tactile stimulation-and FUS- evoked fMRI activation patterns suggests that FUS likely can excite populations of neurons and produce associated spiking activities that may be subsequently transmitted to other functionally related touch regions...
May 22, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29789581/intron-retention-and-nuclear-loss-of-sfpq-are-molecular-hallmarks-of-als
#2
Raphaelle Luisier, Giulia E Tyzack, Claire E Hall, Jamie S Mitchell, Helen Devine, Doaa M Taha, Bilal Malik, Ione Meyer, Linda Greensmith, Jia Newcombe, Jernej Ule, Nicholas M Luscombe, Rickie Patani
Mutations causing amyotrophic lateral sclerosis (ALS) strongly implicate ubiquitously expressed regulators of RNA processing. To understand the molecular impact of ALS-causing mutations on neuronal development and disease, we analysed transcriptomes during in vitro differentiation of motor neurons (MNs) from human control and patient-specific VCP mutant induced-pluripotent stem cells (iPSCs). We identify increased intron retention (IR) as a dominant feature of the splicing programme during early neural differentiation...
May 22, 2018: Nature Communications
https://www.readbyqxmd.com/read/29789530/efficient-blood-brain-barrier-opening-in-primates-with-neuronavigation-guided-ultrasound-and-real-time-acoustic-mapping
#3
Shih-Ying Wu, Christian Aurup, Carlos Sierra Sanchez, Julien Grondin, Wenlan Zheng, Hermes Kamimura, Vincent P Ferrera, Elisa E Konofagou
Brain diseases including neurological disorders and tumors remain under treated due to the challenge to access the brain, and blood-brain barrier (BBB) restricting drug delivery which, also profoundly limits the development of pharmacological treatment. Focused ultrasound (FUS) with microbubbles is the sole method to open the BBB noninvasively, locally, and transiently and facilitate drug delivery, while translation to the clinic is challenging due to long procedure, targeting limitations, or invasiveness of current systems...
May 22, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29788207/potentiating-hsp104-activity-via-phosphomimetic-mutations-in-the-middle-domain
#4
Amber Tariq, JiaBei Lin, Megan M Noll, Mariana P Torrente, Korrie L Mack, Oscar Hernandez Murillo, Meredith E Jackrel, James Shorter
Hsp104 is a hexameric AAA + ATPase and protein disaggregase found in yeast, which can be potentiated via mutations in its middle domain (MD) to counter toxic phase separation by TDP-43, FUS and α-synuclein connected to devastating neurodegenerative disorders. Subtle missense mutations in the Hsp104 MD can enhance activity, indicating that post-translational modification of specific MD residues might also potentiate Hsp104. Indeed, several serine and threonine residues throughout Hsp104 can be phosphorylated in vivo...
August 1, 2018: FEMS Yeast Research
https://www.readbyqxmd.com/read/29774215/importance-of-functional-loss-of-fus-in-ftld-als
#5
REVIEW
Shinsuke Ishigaki, Gen Sobue
Fused in sarcoma (FUS) is an RNA binding protein that regulates RNA metabolism including alternative splicing, transcription, and RNA transportation. FUS is genetically and pathologically involved in frontotemporal lobar degeneration (FTLD)/amyotrophic lateral sclerosis (ALS). Multiple lines of evidence across diverse models suggest that functional loss of FUS can lead to neuronal dysfunction and/or neuronal cell death. Loss of FUS in the nucleus can impair alternative splicing and/or transcription, whereas dysfunction of FUS in the cytoplasm, especially in the dendritic spines of neurons, can cause mRNA destabilization...
2018: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/29772202/rnp-granule-assembly-via-ataxin-2-disordered-domains-is-required-for-long-term-memory-and-neurodegeneration
#6
Baskar Bakthavachalu, Joern Huelsmeier, Indulekha P Sudhakaran, Jens Hillebrand, Amanjot Singh, Arnas Petrauskas, Devasena Thiagarajan, M Sankaranarayanan, Laura Mizoue, Eric N Anderson, Udai Bhan Pandey, Eric Ross, K VijayRaghavan, Roy Parker, Mani Ramaswami
Human Ataxin-2 is implicated in the cause and progression of amyotrophic lateral sclerosis (ALS) and type 2 spinocerebellar ataxia (SCA-2). In Drosophila, a conserved atx2 gene is essential for animal survival as well as for normal RNP-granule assembly, translational control, and long-term habituation. Like its human homolog, Drosophila Ataxin-2 (Atx2) contains polyQ repeats and additional intrinsically disordered regions (IDRs). We demonstrate that Atx2 IDRs, which are capable of mediating liquid-liquid phase transitions in vitro, are essential for efficient formation of neuronal mRNP assemblies in vivo...
May 16, 2018: Neuron
https://www.readbyqxmd.com/read/29760288/-neuropathologic-subtypes-of-frontotemporal-lobar-degeneration
#7
Mari Tada, Akiyoshi Kakita
Frontotemporal lobar degeneration (FTLD) is a heterogeneous disease entity encompassing a wide variety of histopathological features and genetic backgrounds. The last two decades have seen the discovery of causative genes and the identification of relevant proteins. The current histopathological classification is based on the major types of protein deposition in the brain, and most FTLD cases can be placed into one of three pathological subgroups: FTLD-tau, FTLD-TDP, and FTLD-FUS. Further sub-classification within each subgroup is based on the morphology of neuronal and glial inclusions and lesion distribution...
May 2018: Brain and Nerve, Shinkei Kenkyū No Shinpo
https://www.readbyqxmd.com/read/29758948/argyrophilic-grain-pathology-in-frontotemporal-lobar-degeneration-demographic-clinical-neuropathological-and-genetic-features
#8
María José Gil, María Sagrario Manzano, María Luz Cuadrado, Cristina Fernández, Elena Góméz, Carmen Matesanz, Miguel Calero, Alberto Rábano
Frontotemporal lobar degeneration (FTLD) is a clinically, pathologically, and genetically heterogeneous group of disorders that affect the frontal and temporal lobes of the brain. FTLD classification distinguishes three main neuropathological groups: FTLD-tau, FTLD-TDP, and FTLD-FUS. As a four-repeat tauopathy, argyrophilic grain disease (AGD) is included in the FTLD-tau group. AGD may also appear in association with other neuropathological disorders. We describe the demographic, clinical, neuropathological, and genetic characteristics of a series of FTLD cases presenting with AGD...
2018: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29758589/spindle-cell-rhabdomyosarcoma-of-bone-with-fus-tfcp2-fusion-confirmation-of-a-very-recently-described-rhabdomyosarcoma-subtype
#9
Nooshin K Dashti, Rebecca N Wehrs, Brittany C Thomas, Asha Nair, Jaime Davila, Jan C Buckner, Anthony P Martinez, William R Sukov, Kevin C Halling, Benjamin M Howe, Andrew L Folpe
AIMS: Rhabdomyosarcomas of bone are extremely rare, with fewer than 10 reported cases. A very rare subtype of spindle cell/sclerosing rhabdomyosarcoma harboring a FUS-TFCP2 fusion and involving both soft tissue and bone locations has very recently been reported. We report only the fourth case of this unusual, clinically aggressive rhabdomyosarcoma. MATERIAL AND RESULTS: A previously-well 72-year old male presented with a destructive lesion of the mandible. Morphological and immunohistochemical study of a needle biopsy and the subsequent resection showed a spindle cell rhabdomyosarcoma...
May 14, 2018: Histopathology
https://www.readbyqxmd.com/read/29758099/the-reduction-in-treatment-efficiency-at-high-acoustic-powers-during-mr-guided-transcranial-focused-ultrasound-thalamotomy-for-essential-tremor
#10
Alec Hughes, Yuexi Huang, Michael L Schwartz, Kullervo Hynynen
PURPOSE: To analyze clinical data indicating a reduction in the induced energy-temperature efficiency relationship during transcranial focused ultrasound (FUS) essential tremor (ET) thalamotomy treatments at higher acoustic powers, establish its relationship with the spatial distribution of the focal temperature elevation, and explore its cause. METHODS: A retrospective observational study of patients (N = 19) treated between July 2015-August 2016 for Essential Tremor (ET) by FUS thalamotomy was performed...
May 14, 2018: Medical Physics
https://www.readbyqxmd.com/read/29755516/synaptic-paths-to-neurodegeneration-the-emerging-role-of-tdp-43-and-fus-in-synaptic-functions
#11
REVIEW
Shuo-Chien Ling
TAR DNA-binding protein-43 KDa (TDP-43) and fused in sarcoma (FUS) as the defining pathological hallmarks for amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), coupled with ALS-FTD-causing mutations in both genes, indicate that their dysfunctions damage the motor system and cognition. On the molecular level, TDP-43 and FUS participate in the biogenesis and metabolism of coding and noncoding RNAs as well as in the transport and translation of mRNAs as part of cytoplasmic mRNA-ribonucleoprotein (mRNP) granules...
2018: Neural Plasticity
https://www.readbyqxmd.com/read/29740276/cortical-hemodynamic-responses-under-focused-ultrasound-stimulation-using-real-time-laser-speckle-contrast-imaging
#12
Yi Yuan, Yanchao Zhao, Hongshuai Jia, Mengyang Liu, Shuo Hu, Yingwei Li, Xiaoli Li
Although there is increasing use of focused ultrasound stimulation (FUS) in brain studies, the real-time changes of the cerebral blood flow (CBF) due to FUS remain unclear. In this study, we developed a novel scheme combining FUS and laser speckle contrast imaging, which can be used to measure the CBF caused by FUS in real time. The results showed that the change of CBF increased from 0 to 30 s and reached up to the maximum of 115.1 ± 6.5% at 30 s and then decreased gradually from 30 to 60 s. This study demonstrates that FUS was able to increase CBF and alter cortical hemodynamic responses, which indicates that FUS is a potential non-invasive method to study ischemic stroke rehabilitation...
2018: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/29734651/acetylation-disfavors-tau-phase-separation
#13
Josephine C Ferreon, Antrix Jain, Kyoung-Jae Choi, Phoebe S Tsoi, Kevin R MacKenzie, Sung Yun Jung, Allan Chris Ferreon
Neuropathological aggregates of the intrinsically disordered microtubule-associated protein Tau are hallmarks of Alzheimer’s disease, with decades of research devoted to studying the protein’s aggregation properties both in vitro and in vivo. Recent demonstrations that Tau is capable of undergoing liquid-liquid phase separation (LLPS) reveal the possibility that protein-enriched phase separated compartments could serve as initiation sites for Tau aggregation, as shown for other amyloidogenic proteins, such as the Fused in Sarcoma protein (FUS) and TAR DNA-binding protein-43 (TDP-43)...
May 4, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29728564/nuclear-egress-of-tdp-43-and-fus-occurs-independently-of-exportin-1-crm1
#14
Helena Ederle, Christina Funk, Claudia Abou-Ajram, Saskia Hutten, Eva B E Funk, Ralph H Kehlenbach, Susanne M Bailer, Dorothee Dormann
TDP-43 and FUS are nuclear proteins with multiple functions in mRNA processing. They play key roles in ALS (amyotrophic lateral sclerosis) and FTD (frontotemporal dementia), where they are partially lost from the nucleus and aggregate in the cytoplasm of neurons and glial cells. Defects in nucleocytoplasmic transport contribute to this pathology, hence nuclear import of both proteins has been studied in detail. However, their nuclear export routes remain poorly characterized and it is unclear whether aberrant nuclear export contributes to TDP-43 or FUS pathology...
May 4, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29728455/microtubules-as-platforms-for-probing-liquid-liquid-phase-separation-in-cells-application-to-rna-binding-proteins
#15
Alexandre Maucuer, Bénédicte Desforges, Vandana Joshi, Mirela Boca, Dmitry Kretov, Loic Hamon, Ahmed Bouhss, Patrick A Curmi, David Pastré
Liquid-liquid phase separation enables compartmentalization of biomolecules in cells, notably RNA and associated proteins in the nucleus. Besides critical functions in RNA processing, there is a major interest in deciphering the molecular mechanisms of compartmentalization orchestrated by RNA-binding proteins such as TDP-43 and FUS due to their link to neuron diseases. However, tools for probing compartmentalization in cells are lacking. Here we developed a method to analyze the mixing:demixing of two different phases in a cellular context...
May 4, 2018: Journal of Cell Science
https://www.readbyqxmd.com/read/29723616/image-guided-thermosensitive-liposomes-for-focused-ultrasound-drug-delivery-using-nirf-labelled-lipids-and-topotecan-to-visualise-the-effects-of-hyperthermia-in-tumours
#16
Miguel N Centelles, Michael Wright, Po-Wah So, Maral Amrahli, Xiao Yun Xu, Justin Stebbing, Andrew D Miller, Wladyslaw Gedroyc, Maya Thanou
Image guided drug delivery using imageable thermosensitive liposomes (iTSLs) and high intensity focused ultrasound (FUS or HIFU) has attracted interest as a novel and non-invasive route to targeted delivery of anti-cancer therapeutics. FUS-induced hyperthermia is used as an externally applied "trigger" for the release of a drug cargo from within thermosensitive drug carriers. It is suggested that sub-ablative hyperthermia significantly modifies the permeability of tumour vasculature and enhances nanoparticle uptake...
April 30, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29723523/the-physiological-and-pathological-biophysics-of-phase-separation-and-gelation-of-rna-binding-proteins-in-amyotrophic-lateral-sclerosis-and-fronto-temporal-lobar-degeneration
#17
Peter St George-Hyslop, Julie Qiaojin Lin, Akinori Miyashita, Emma C Phillips, Seema Qamar, Suzanne J Randle, GuoZhen Wang
Many RNA binding proteins, including FUS, contain moderately repetitive, low complexity, intrinsically disordered domains. These sequence motifs have recently been found to underpin reversible liquid: liquid phase separation and gelation of these proteins, permitting them to reversibly transition from a monodispersed state to liquid droplet- or hydrogel-like states. This function allows the proteins to serve as scaffolds for the formation of reversible membraneless intracellular organelles such as nucleoli, stress granules and neuronal transport granules...
April 30, 2018: Brain Research
https://www.readbyqxmd.com/read/29721406/focused-ultrasound-augmented-delivery-of-biodegradable-multifunctional-nanoplatforms-for-imaging-guided-brain-tumor-treatment
#18
Meiying Wu, Wenting Chen, Yu Chen, Haixian Zhang, Chengbo Liu, Zhiting Deng, Zonghai Sheng, Jingqin Chen, Xin Liu, Fei Yan, Hairong Zheng
The blood brain barrier is the main obstacle to delivering diagnostic and therapeutic agents to the diseased sites of brain. It is still of great challenge for the combined use of focused ultrasound (FUS) and theranostic nanotechnology to achieve noninvasive and localized delivery of chemotherapeutic drugs into orthotopic brain tumor. In this work, a unique theranostic nanoplatform for highly efficient photoacoustic imaging - guided chemotherapy of brain tumor both in vitro and in vivo, which is based on the utilization of hollow mesoporous organosilica nanoparticles (HMONs) to integrate ultrasmall Cu2- x Se particles on the surface and doxorubicin inside the hollow interior, is synthesized...
April 2018: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
https://www.readbyqxmd.com/read/29712963/publisher-correction-functional-interaction-between-fus-and-smn-underlies-sma-like-splicing-changes-in-wild-type-hfus-mice
#19
Alessia Mirra, Simona Rossi, Silvia Scaricamazza, Michela Di Salvio, Illari Salvatori, Cristiana Valle, Paola Rusmini, Angelo Poletti, Gianluca Cestra, Maria Teresa Carrì, Mauro Cozzolino
A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
April 30, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29700310/focused-ultrasound-enabled-brain-tumor-liquid-biopsy
#20
Lifei Zhu, Galen Cheng, Dezhuang Ye, Arash Nazeri, Yimei Yue, Weijun Liu, Xiaowei Wang, Gavin P Dunn, Allegra A Petti, Eric C Leuthardt, Hong Chen
Although blood-based liquid biopsies have emerged as a promising non-invasive method to detect biomarkers in various cancers, limited progress has been made for brain tumors. One major obstacle is the blood-brain barrier (BBB), which hinders efficient passage of tumor biomarkers into the peripheral circulation. The objective of this study was to determine whether FUS in combination with microbubbles can enhance the release of biomarkers from the brain tumor to the blood circulation. Two glioblastoma tumor models (U87 and GL261), developed by intracranial injection of respective enhanced green fluorescent protein (eGFP)-transduced glioblastoma cells, were treated by FUS in the presence of systemically injected microbubbles...
April 26, 2018: Scientific Reports
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