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https://www.readbyqxmd.com/read/29223504/potential-pathogenic-mechanisms-underlying-fragile-x-tremor-ataxia-syndrome-ran-translation-and-or-rna-gain-of-function
#1
REVIEW
Manon Boivin, Rob Willemsen, Renate K Hukema, Chantal Sellier
Fragile X-associated tremor/ataxia syndrome (FXTAS) is an inherited neurodegenerative disease caused by an expansion of 55-200 CGG repeats located in the FMR1 gene. The main clinical and neuropathological features of FXTAS are progressive intention tremor and gait ataxia associated with brain atrophy, neuronal cell loss and presence of ubiquitin-positive intranuclear inclusions in both neurons and astrocytes. At the molecular level, FXTAS is characterized by increased expression of FMR1 sense and antisense RNA containing expanded CGG or GGC repeats, respectively...
December 6, 2017: European Journal of Medical Genetics
https://www.readbyqxmd.com/read/29222490/ran-translation-at-c9orf72-associated-repeat-expansions-is-selectively-enhanced-by-the-integrated-stress-response
#2
Katelyn M Green, M Rebecca Glineburg, Michael G Kearse, Brittany N Flores, Alexander E Linsalata, Stephen J Fedak, Aaron C Goldstrohm, Sami J Barmada, Peter K Todd
Repeat-associated non-AUG (RAN) translation allows for unconventional initiation at disease-causing repeat expansions. As RAN translation contributes to pathogenesis in multiple neurodegenerative disorders, determining its mechanistic underpinnings may inform therapeutic development. Here we analyze RAN translation at G4C2 repeat expansions that cause C9orf72-associated amyotrophic lateral sclerosis and frontotemporal dementia (C9RAN) and at CGG repeats that cause fragile X-associated tremor/ataxia syndrome...
December 8, 2017: Nature Communications
https://www.readbyqxmd.com/read/29211764/identification-expression-and-functional-characterization-of-m4l-a-muscarinic-acetylcholine-m4-receptor-splice-variant
#3
Douglas A Schober, Carrie H Croy, Cara L Ruble, Ran Tao, Christian C Felder
Rodent genomic alignment sequences support a 2-exon model for muscarinic M4 receptor. Using this model a novel N-terminal extension was discovered in the human muscarinic acetylcholine M4 receptor. An open reading frame was discovered in the human, mouse and rat with a common ATG (methionine start codon) that extended the N-terminus of the muscarinic acetylcholine M4 receptor subtype by 155 amino acids resulting in a longer variant. Transcriptional evidence for this splice variant was confirmed by RNA-Seq and RT-PCR experiments performed from human donor brain prefrontal cortices...
2017: PloS One
https://www.readbyqxmd.com/read/29209303/ph-stress-induced-cooperation-between-rhodococcus-ruber-yyl-and-bacillus-cereus-mly1-in-biodegradation-of-tetrahydrofuran
#4
Zubi Liu, Zhixing He, Hui Huang, Xuebin Ran, Adebanjo O Oluwafunmilayo, Zhenmei Lu
Microbial consortia consisting of cooperational strains exhibit biodegradation performance superior to that of single microbial strains and improved remediation efficiency by relieving the environmental stress. Tetrahydrofuran (THF), a universal solvent widely used in chemical and pharmaceutical synthesis, significantly affects the environment. As a refractory pollutant, THF can be degraded by some microbial strains under suitable conditions. There are often a variety of stresses, especially pH stress, that inhibit the THF-degradation efficiency of microbial consortia...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29201140/expression-of-the-entire-polyhydroxybutyrate-operon-of-ralstonia-eutropha-in-plants
#5
Rita Mozes-Koch, Edna Tanne, Alexandra Brodezki, Ran Yehuda, Ofer Gover, Haim D Rabinowitch, Ilan Sela
Background: Previously we demonstrated that an entire bacterial operon (the PRN operon) is expressible in plants when driven by the Tomato -yellow-leaf-curl-virus (TYLCV) -derived universal vector IL-60.Petroleum-derived plastics are not degradable, and are therefore harmful to the environment. Fermentation of bacteria carrying operons for polyhydroxyalkanoates (PHAs) produces degradable bioplastics which are environmentally friendly. However, bacterial production of bioplastics is not cost-effective, and attention is turning to their production in plants...
2017: Journal of Biological Engineering
https://www.readbyqxmd.com/read/29190340/continuous-glucose-monitoring-for-hypoglycemia-avoidance-and-glucose-counterregulation-in-long-standing-type-1-diabetes
#6
Michael R Rickels, Amy J Peleckis, Cornelia Dalton-Bakes, Joseph R Naji, Nina A Ran, Huong-Lan Nguyen, Shannon O'Brien, Sanjian Chen, Insup Lee, Mark H Schutta
Context: Patients with long standing type 1 diabetes (T1D) are at increased risk for severe hypoglycemia due to defects in glucose counterregulation and hypoglycemia symptom recognition, in part mediated through exposure to hypoglycemia. Objective: To determine whether implementation of real-time continuous glucose monitoring (CGM) as a strategy for hypoglycemia avoidance could improve glucose counterregulation in patients with long standing T1D complicated by hypoglycemia unawareness...
November 28, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29165995/magnetic-particle-imaging-for-highly-sensitive-quantitative-and-safe-in-vivo-gut-bleed-detection-in-a-murine-model
#7
Elaine Y Yu, Prashant Chandrasekharan, Ran Berzon, Zhi Wei Tay, Xinyi Y Zhou, Amit P Khandhar, R Matthew Ferguson, Scott J Kemp, Bo Zheng, Patrick W Goodwill, Michael F Wendland, Kannan M Krishnan, Spencer Behr, Jonathan Carter, Steven M Conolly
Gastrointestinal (GI) bleeding causes more than 300,000 hospitalizations per year in the United States. Imaging plays a crucial role in accurately locating the source of the bleed for timely intervention. Magnetic Particle Imaging (MPI) is an emerging clinically translatable imaging modality that images superparamagnetic iron-oxide (SPIO) tracers with extraordinary contrast and sensitivity. This linearly quantitative modality has zero background tissue signal and zero signal depth attenuation. MPI is also safe: there is zero ionizing radiation exposure to the patient and clinically approved tracers can be used with MPI...
November 22, 2017: ACS Nano
https://www.readbyqxmd.com/read/29149615/rethinking-unconventional-translation-in-neurodegeneration
#8
REVIEW
Fen-Biao Gao, Joel D Richter, Don W Cleveland
Eukaryotic translation is tightly regulated to ensure that protein production occurs at the right time and place. Recent studies on abnormal repeat proteins, especially in age-dependent neurodegenerative diseases caused by nucleotide repeat expansion, have highlighted or identified two forms of unconventional translation initiation: usage of AUG-like sites (near cognates) or repeat-associated non-AUG (RAN) translation. We discuss how repeat proteins may differ due to not just unconventional initiation, but also ribosomal frameshifting and/or imperfect repeat DNA replication, expansion, and repair, and we highlight how research on translation of repeats may uncover insights into the biology of translation and its contribution to disease...
November 16, 2017: Cell
https://www.readbyqxmd.com/read/29146462/individual-serum-bile-acid-profiling-in-rats-aids-in-human-risk-assessment-of-drug-induced-liver-injury-due-to-bsep-inhibition
#9
Steven Cepa, David Potter, Lisa Wong, Leah Schutt, Jacqueline Tarrant, Jodie Pang, Xiaolin Zhang, Roxanne Andaya, Laurent Salphati, Yingqing Ran, Le An, Ryan Morgan, Jonathan Maher
Drug-induced liver injury (DILI) has been the most frequent cause of post-marketing drug withdrawals in the last 50years. The multifactorial nature of events that precede severe liver injury in human patients is difficult to model in rodents due to a variety of confounding or contributing factors that include disease state, concurrent medications, and translational species differences. In retrospective analyses, a consistent risk factor for DILI has been the inhibition of the Bile Salt Export Pump (BSEP). One compound known for potent BSEP inhibition and severe DILI is troglitazone...
November 13, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29125328/automated-retrieval-of-radiotherapy-data-for-clinical-trials-audit-and-research
#10
Marina Romanchikova, Karl Harrison, Neil G Burnet, Andrew Fc Hoole, Michael Pf Sutcliffe, Michael Andrew Parker, Rajesh Jena, Simon J Thomas
OBJECTIVE: To enable fast and customisable automated collection of radiotherapy data from tomotherapy storage. METHODS: Human-readable data maps (TagMaps) were created to generate DICOM-RT data from tomotherapy archives, and provided access to "hidden" information comprising delivery sinograms, positional corrections and adaptive-RT doses. RESULTS: 797 datasets totalling 25,000 scans were batch-exported in 31.5 hours. All archived information was restored, including the data not available via commercial software...
November 10, 2017: British Journal of Radiology
https://www.readbyqxmd.com/read/29078961/new-parameters-describing-how-knee-ligaments-carry-force-in-situ-predict-interspecimen-variations-in-laxity-during-simulated-clinical-exams
#11
Carl W Imhauser, Robert N Kent, James Boorman-Padgett, Ran Thein, Thomas L Wickiewicz, Andrew D Pearle
Knee laxity, defined as the net translation or rotation of the tibia relative to the femur in a given direction in response to an applied load, is highly variable from person to person. High levels of knee laxity as assessed during routine clinical exams are associated with first-time ligament injury and graft reinjury following reconstruction. During laxity exams, ligaments carry force to resist the applied load; however, relationships between intersubject variations in knee laxity and variations in how ligaments carry force as the knee moves through its passive envelope of motion, which we refer to as ligament engagement, are not well established...
October 7, 2017: Journal of Biomechanics
https://www.readbyqxmd.com/read/29069627/src-sumoylation-inhibits-tumor-growth-via-decreasing-fak-y925-phosphorylation
#12
Jing Wang, Rong Deng, Nan Cui, Hailong Zhang, Tianqi Liu, Jinzhuo Dou, Xian Zhao, Ran Chen, Yanli Wang, Jianxiu Yu, Jian Huang
Src, a non-receptor tyrosine kinase protein, plays a critical role in cell proliferation and tumorigenesis. SUMOylation, a reversible ubiquitination-like post-translational modification, is vital for tumor progression. Here, we report that the Src protein can be SUMOylated at lysine 318 both in vitro and in vivo. Hypoxia can induce a decrease of Src SUMOylation along with an increase of Y419 phosphorylation, a phosphorylation event required for Src activation. On the other hand, treatment with hydrogen peroxide can enhance Src SUMOylation...
October 22, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/29049353/should-preventive-antibiotics-be-used-in-patients-with-acute-stroke-a-systematic-review-and-meta-analysis-of-randomized-controlled-trials
#13
REVIEW
Feng Zheng, Niklas von Spreckelsen, Xintong Zhang, Pantelis Stavrinou, Marco Timmer, Christian Dohmen, Roland Goldbrunner, Fang Cao, Qiang Zhang, Qishan Ran, Gang Li, Ruiming Fan, Shengtao Yao, Boris Krischek
BACKGROUND: Infection is a common complication in acute stroke. Whether or not preventive antibiotics reduce the risk of infection or even lead to a favorable outcome and reduction of mortality after a stroke still remains equivocal. This review was performed to update the current knowledge on the effect and possible benefits of prophylactic antibiotic therapy in patients with stroke. METHODS: A systematic review and meta-analysis of preventive antibiotics`effect on the incidence of infection, favorable outcome (mRS≤2) and mortality in patients with acute stroke is performed with relevant randomized controlled trials...
2017: PloS One
https://www.readbyqxmd.com/read/29040603/mitosis-specific-acetylation-tunes-ran-effector-binding-for-chromosome-segregation
#14
Xiaoling Bao, Heng Liu, Xing Liu, Ke Ruan, Yonghui Zhang, Zhiyong Zhang, Qi Hu, Ying Liu, Saima Akram, Jiahai Zhang, Qingguo Gong, Wenwen Wang, Xiao Yuan, Jian Li, Lingli Zhao, Zhen Dou, Ruijun Tian, Xuebiao Yao, Jihui Wu, Yunyu Shi
Stable transmission of genetic information during cell division requires faithful mitotic spindle assembly and chromosome segregation. The Ran GTPase plays a key role in mitotic spindle assembly. However, how the generation of a chemical gradient of Ran-GTP at the spindle is coupled to mitotic post-translational modifications has never been characterized. Here, we solved the complex structure of Ran with the nucleotide release factor Mog1 and delineated a novel mitosis-specific acetylation-regulated Ran-Mog1 interaction during chromosome segregation...
October 6, 2017: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/29034894/induced-pluripotent-stem-cells-derived-from-a-patient-with-familial-idiopathic-basal-ganglia-calcification-ibgc-caused-by-a-mutation-in-slc20a2-gene
#15
Shin-Ichiro Sekine, Takayuki Kondo, Nagahisa Murakami, Keiko Imamura, Takako Enami, Ran Shibukawa, Kayoko Tsukita, Misato Funayama, Masatoshi Inden, Hisaka Kurita, Isao Hozumi, Haruhisa Inoue
Idiopathic basal ganglia calcification (IBGC), also known as Fahr disease or primary familial brain calcifications (PFBC), is a rare neurodegenerative disorder characterized by calcium deposits in basal ganglia and other brain regions, causing neuropsychiatric and motor symptoms. We established human induced pluripotent stem cells (iPSCs) from an IBGC patient. The established IBGC-iPSCs carried SLC20A2 c.1848G>A mutation (p.W616* of translated protein PiT2), and also showed typical iPSC morphology, pluripotency markers, normal karyotype, and the ability of in vitro differentiation into three-germ layers...
October 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28990062/regulation-of-m1%C3%A2-type-and-m2%C3%A2-type-macrophage-polarization-in-raw264-7-cells-by-galectin%C3%A2-9
#16
Ran Lv, Qi Bao, Yan Li
Generally considered as a potent pro‑inflammatory signal, β‑galactosidelectin suppresses T cell receptor activation, can both promote and inhibit integrin‑mediated adhesion and is required in nuclear pre‑mRNA splicing. Galectin‑9 (Gal‑9), a member of β‑galactoside lectin, is involved many processes of T cell‑mediated diseases (such as autoimmune diseases and asthma) and immunomodulation of macrophages. Macrophages are involved in the occurrence of inflammation, development and digestion and other stages...
December 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28981631/uv-radiation-induced-sumoylation-of-ddb2-regulates-nucleotide-excision-repair
#17
Chunhua Han, Ran Zhao, John Kroger, Jinshan He, Gulzar Wani, Qi-En Wang, Altaf A Wani
Subunit 2 of DNA damage-binding protein complex (DDB2) is an early sensor of nucleotide excision repair (NER) pathway for eliminating DNA damage induced by UV radiation (UVR) and cisplatin treatments of mammalian cells. DDB2 is modified by ubiquitin and poly(ADP-ribose) (PAR) in response to UVR, and these modifications play a crucial role in regulating NER. Here, using immuno-analysis of irradiated cell extracts, we have identified multiple post-irradiation modifications of DDB2 protein. Interestingly, although the DNA lesions induced by both UVR and cisplatin are corrected by NER, only the UV irradiation, but not the cisplatin treatment, induces any discernable DDB2 modifications...
October 1, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/28977986/interplay-between-apoptosis-and-autophagy-in-colorectal-cancer
#18
Hao-Ran Qian, Zhao-Qi Shi, He-Pan Zhu, Li-Hu Gu, Xian-Fa Wang, Yi Yang
Autophagy and apoptosis are two pivotal mechanisms in mediating cell survival and death. Cross-talk of autophagy and apoptosis has been documented in the tumorigenesis and progression of cancer, while the interplay between the two pathways in colorectal cancer (CRC) has not yet been comprehensively summarized. In this study, we outlined the basis of apoptosis and autophagy machinery firstly, and then reviewed the recent evidence in cellular settings or animal studies regarding the interplay between them in CRC...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28977617/structural-insights-into-species-specific-features-of-the-ribosome-from-the-human-pathogen-mycobacterium-tuberculosis
#19
Kailu Yang, Jeng-Yih Chang, Zhicheng Cui, Xiaojun Li, Ran Meng, Lijun Duan, Jirapat Thongchol, Joanita Jakana, Christoph M Huwe, James C Sacchettini, Junjie Zhang
Ribosomes from Mycobacterium tuberculosis (Mtb) possess species-specific ribosomal RNA (rRNA) expansion segments and ribosomal proteins (rProtein). Here, we present the near-atomic structures of the Mtb 50S ribosomal subunit and the complete Mtb 70S ribosome, solved by cryo-electron microscopy. Upon joining of the large and small ribosomal subunits, a 100-nt long expansion segment of the Mtb 23S rRNA, named H54a or the 'handle', switches interactions from with rRNA helix H68 and rProtein uL2 to with rProtein bS6, forming a new intersubunit bridge 'B9'...
October 13, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28973350/c9orf72-poly-ga-ran-translated-protein-plays-a-key-role-in-amyotrophic-lateral-sclerosis-via-aggregation-and-toxicity
#20
Youn-Bok Lee, Pranetha Baskaran, Jorge Gomez, Han-Jou Chen, Agnes Nishimura, Bradley Smith, Claire Troakes, Yoshitsugu Adachi, Alan Stepto, Leonard Petrucelli, Jean-Marc Gallo, Frank Hirth, Boris Rogelj, Sarah Guthrie, Christopher E Shaw
An intronic GGGGCC (G4C2) hexanucleotide repeat expansion inC9orf72 is the most common genetic cause of Amyotrophic Lateral Sclerosis and Frontotemporal Dementia (C9ALS/FTD). Repeat-associated non-AUG (RAN) translation of G4C2 RNA can result in five different dipeptide repeat proteins (DPR: poly GA, poly GP, poly GR, poly PA, and poly PR), which aggregate into neuronal cytoplasmic and nuclear inclusions in affected patients, however their contribution to disease pathogenesis remains controversial. We show that among the DPR proteins, expression of poly GA in a cell culture model activates programmed cell death and TDP-43 cleavage in a dose-dependent manner...
September 13, 2017: Human Molecular Genetics
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