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https://www.readbyqxmd.com/read/29453961/repeat-associated-non-aug-ran-translation-and-other-molecular-mechanisms-in-fragile-x-tremor-ataxia-syndrome
#1
M Rebecca Glineburg, Peter K Todd, Nicolas Charlet-Berguerand, Chantal Sellier
Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset inherited neurodegenerative disorder characterized by progressive intention tremor, gait ataxia and dementia associated with mild brain atrophy. The cause of FXTAS is a premutation expansion, of 55 to 200 CGG repeats localized within the 5'UTR of FMR1. These repeats are transcribed in the sense and antisense directions into mutants RNAs, which have increased expression in FXTAS. Furthermore, CGG sense and CCG antisense expanded repeats are translated into novel proteins despite their localization in putatively non-coding regions of the transcript...
February 14, 2018: Brain Research
https://www.readbyqxmd.com/read/29453960/synaptic-dysfunction-and-altered-excitability-in-c9orf72-als-ftd
#2
Alexander Starr, Rita Sattler
Amyotrophic lateral sclerosis (ALS) is characterized by a progressive degeneration of upper and lower motor neurons, resulting in fatal paralysis due to denervation of the muscle. Due to genetic, pathological and symptomatic overlap, ALS is now considered a spectrum disease together with frontotemporal dementia (FTD), the second most common cause of dementia in individuals under the age of 65. Interestingly, in both diseases, there is a large prevalence of RNA binding proteins (RBPs) that are mutated and considered disease-causing, or whose dysfunction contribute to disease pathogenesis...
February 14, 2018: Brain Research
https://www.readbyqxmd.com/read/29427099/rna-related-pathology-in-huntington-s-disease
#3
Andreas Neueder, Gillian P Bates
This chapter summarises research investigating the expression of huntingtin sense and anti-sense transcripts, the effect of the mutation on huntingtin processing as well as the more global effect of the mutation on the coding and non-coding transcriptomes. The huntingtin gene is ubiquitously expressed, although expression levels vary between tissues and cell types. A SNP that affects NF-ĸB binding in the huntingtin promoter modulates the expression level of huntingtin transcripts and is associated with the age of disease onset...
2018: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29427077/post-translational-regulation-of-the-maternal-to-zygotic-transition
#4
REVIEW
Chao Liu, Yanjie Ma, Yongliang Shang, Ran Huo, Wei Li
The maternal-to-zygotic transition (MZT) is essential for the developmental control handed from maternal products to newly synthesized zygotic genome in the earliest stages of embryogenesis, including maternal component (mRNAs and proteins) degradation and zygotic genome activation (ZGA). Various protein post-translational modifications have been identified during the MZT, such as phosphorylation, methylation and ubiquitination. Precise post-translational regulation mechanisms are essential for the timely transition of early embryonic development...
February 9, 2018: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29400721/orthogonal-vector-algorithm-to-obtain-the-solar-vector-using-the-single-scattering-rayleigh-model
#5
Yinlong Wang, Jinkui Chu, Ran Zhang, Chao Shi
Information obtained from a polarization pattern in the sky provides many animals like insects and birds with vital long-distance navigation cues. The solar vector can be derived from the polarization pattern using the single-scattering Rayleigh model. In this paper, an orthogonal vector algorithm, which utilizes the redundancy of the single-scattering Rayleigh model, is proposed. We use the intersection angles between the polarization vectors as the main criteria in our algorithm. The assumption that all polarization vectors can be considered coplanar is used to simplify the three-dimensional (3D) problem with respect to the polarization vectors in our simulation...
February 1, 2018: Applied Optics
https://www.readbyqxmd.com/read/29388770/a-dual-reporter-iodinated-labeling-reagent-for-cancer-positron-emission-tomography-imaging-and-fluorescence-guided-surgery
#6
Zhi Lu, Truc Thuy Pham, Vineeth Rajkumar, Zilin Yu, R Barbara Pedley, Erik Årstad, John Maher, Ran Yan
The combination of early diagnosis and complete surgical resection offers the greatest prospect of curative cancer treatment. An iodine-124/fluorescein-based dual-modality labeling reagent, 124I-Green, constitutes a generic tool for one-step installation of a positron emission tomography (PET) and a fluorescent reporter to any cancer-specific antibody. The resulting antibody conjugate would allow both cancer PET imaging and intraoperative fluorescence-guided surgery. 124I-Green was synthesized in excellent radiochemical yields of 92±5% (n=4) determined by HPLC with an improved one-pot three-component radioiodination reaction...
February 1, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29346752/epitranscriptomic-m6a-regulation-of-axon-regeneration-in-the-adult-mammalian-nervous-system
#7
Yi-Lan Weng, Xu Wang, Ran An, Jessica Cassin, Caroline Vissers, Yuanyuan Liu, Yajing Liu, Tianlei Xu, Xinyuan Wang, Samuel Zheng Hao Wong, Jessica Joseph, Louis C Dore, Qiang Dong, Wei Zheng, Peng Jin, Hao Wu, Bin Shen, Xiaoxi Zhuang, Chuan He, Kai Liu, Hongjun Song, Guo-Li Ming
N6-methyladenosine (m6A) affects multiple aspects of mRNA metabolism and regulates developmental transitions by promoting mRNA decay. Little is known about the role of m6A in the adult mammalian nervous system. Here we report that sciatic nerve lesion elevates levels of m6A-tagged transcripts encoding many regeneration-associated genes and protein translation machinery components in the adult mouse dorsal root ganglion (DRG). Single-base resolution m6A-CLIP mapping further reveals a dynamic m6A landscape in the adult DRG upon injury...
January 17, 2018: Neuron
https://www.readbyqxmd.com/read/29323119/cug-initiation-and-frameshifting-enable-production-of-dipeptide-repeat-proteins-from-als-ftd-c9orf72-transcripts
#8
Ricardos Tabet, Laure Schaeffer, Fernande Freyermuth, Melanie Jambeau, Michael Workman, Chao-Zong Lee, Chun-Chia Lin, Jie Jiang, Karen Jansen-West, Hussein Abou-Hamdan, Laurent Désaubry, Tania Gendron, Leonard Petrucelli, Franck Martin, Clotilde Lagier-Tourenne
Expansion of G4C2 repeats in the C9ORF72 gene is the most prevalent inherited form of amyotrophic lateral sclerosis and frontotemporal dementia. Expanded transcripts undergo repeat-associated non-AUG (RAN) translation producing dipeptide repeat proteins from all reading frames. We determined cis-factors and trans-factors influencing translation of the human C9ORF72 transcripts. G4C2 translation operates through a 5'-3' cap-dependent scanning mechanism, requiring a CUG codon located upstream of the repeats and an initiator Met-tRNAMeti...
January 11, 2018: Nature Communications
https://www.readbyqxmd.com/read/29302060/c9orf72-ggggcc-repeat-associated-non-aug-translation-is-upregulated-by-stress-through-eif2%C3%AE-phosphorylation
#9
Weiwei Cheng, Shaopeng Wang, Alexander A Mestre, Chenglai Fu, Andres Makarem, Fengfan Xian, Lindsey R Hayes, Rodrigo Lopez-Gonzalez, Kevin Drenner, Jie Jiang, Don W Cleveland, Shuying Sun
Hexanucleotide repeat expansion in C9ORF72 is the most frequent cause of both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Here we demonstrate that the repeat-associated non-AUG (RAN) translation of (GGGGCC) n -containing RNAs into poly-dipeptides can initiate in vivo without a 5'-cap. The primary RNA substrate for RAN translation of C9ORF72 sense repeats is shown to be the spliced first intron, following its excision from the initial pre-mRNA and transport to the cytoplasm. Cap-independent RAN translation is shown to be upregulated by various stress stimuli through phosphorylation of the α subunit of eukaryotic initiation factor-2 (eIF2α), the core event of an integrated stress response (ISR)...
January 4, 2018: Nature Communications
https://www.readbyqxmd.com/read/29223504/potential-pathogenic-mechanisms-underlying-fragile-x-tremor-ataxia-syndrome-ran-translation-and-or-rna-gain-of-function
#10
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
#11
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
#12
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
#13
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
#14
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
#15
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 because of defects in glucose counterregulation and recognition of hypoglycemia symptoms, 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 and hypoglycemia unawareness...
January 1, 2018: 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
#16
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
#17
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
#18
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
#19
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
#20
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
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