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https://www.readbyqxmd.com/read/28343865/regulatory-role-of-rna-chaperone-tdp-43-for-rna-misfolding-and-repeat-associated-translation-in-sca31
#1
Taro Ishiguro, Nozomu Sato, Morio Ueyama, Nobuhiro Fujikake, Chantal Sellier, Akemi Kanegami, Eiichi Tokuda, Bita Zamiri, Terence Gall-Duncan, Mila Mirceta, Yoshiaki Furukawa, Takanori Yokota, Keiji Wada, J Paul Taylor, Christopher E Pearson, Nicolas Charlet-Berguerand, Hidehiro Mizusawa, Yoshitaka Nagai, Kinya Ishikawa
Microsatellite expansion disorders are pathologically characterized by RNA foci formation and repeat-associated non-AUG (RAN) translation. However, their underlying pathomechanisms and regulation of RAN translation remain unknown. We report that expression of expanded UGGAA (UGGAAexp) repeats, responsible for spinocerebellar ataxia type 31 (SCA31) in Drosophila, causes neurodegeneration accompanied by accumulation of UGGAAexp RNA foci and translation of repeat-associated pentapeptide repeat (PPR) proteins, consistent with observations in SCA31 patient brains...
March 18, 2017: Neuron
https://www.readbyqxmd.com/read/28337854/silk-fibroin-biomaterial-shows-safe-and-effective-wound-healing-in-animal-models-and-a-randomized-controlled-clinical-trial
#2
Wei Zhang, Longkun Chen, Jialin Chen, Lingshuang Wang, Xuexian Gui, Jisheng Ran, Guowei Xu, Hongshi Zhao, Mengfeng Zeng, Junfeng Ji, Li Qian, Jianda Zhou, Hongwei Ouyang, Xiaohui Zou
Due to its excellent biological and mechanical properties, silk fibroin has been intensively explored for tissue engineering and regenerative medicine applications. However, lack of translational evidence has hampered its clinical application for tissue repair. Here a silk fibroin film is developed and its translational potential is investigated for skin repair by performing comprehensive preclinical and clinical studies to fully evaluate its safety and effectiveness. The silk fibroin film fabricated using all green chemistry approaches demonstrates remarkable characteristics, including transmittance, fluid handling capacity, moisture vapor permeability, waterproofness, bacterial barrier properties, and biocompatibility...
March 24, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/28301205/intratendon-delivery-of-leukocyte-poor-platelet-rich-plasma-improves-healing-compared-with-leukocyte-rich-platelet-rich-plasma-in-a-rabbit-achilles-tendinopathy-model
#3
Ruijian Yan, Yanjia Gu, Jisheng Ran, Yejun Hu, Zefeng Zheng, Mengfeng Zeng, Boonchin Heng, Xiao Chen, Zi Yin, Weishan Chen, Weiliang Shen, Hongwei Ouyang
BACKGROUND: Chronic tendinopathy is a commonly occurring clinical problem that affects both athletes and inactive middle-aged patients. Although some studies have shown that different platelet-rich plasma (PRP) preparations could exert various therapeutic effects in vitro, the role of leukocytes in PRP has not yet been defined under tendinopathy conditions in vivo. PURPOSE: This study compared the effects of the intratendon delivery of leukocyte-poor PRP (Lp-PRP) versus leukocyte-rich PRP (Lr-PRP) in a rabbit chronic tendinopathy model in vivo...
March 1, 2017: American Journal of Sports Medicine
https://www.readbyqxmd.com/read/28297584/improvement-of-in-vitro-three-dimensional-cartilage-regeneration-by-a-novel-hydrostatic-pressure-bioreactor
#4
Jie Chen, Zhaoyuan Yuan, Yu Liu, Rui Zheng, Yao Dai, Ran Tao, Huitang Xia, Hairong Liu, Zhiyong Zhang, Wenjie Zhang, Wei Liu, Yilin Cao, Guangdong Zhou
In vitro three-dimensional (3D) cartilage regeneration is a promising strategy for repair of cartilage defects. However, inferior mechanical strength and tissue homogeneity greatly restricted its clinical translation. Simulation of mechanical stress through a bioreactor is an important approach for improving in vitro cartilage regeneration. The current study developed a hydrostatic pressure (HP) bioreactor based on a novel pressure-transmitting mode achieved by slight deformation of a flexible membrane in a completely sealed stainless steel device...
March 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28297578/%C3%AE-elemene-selectively-inhibits-the-proliferation-of-glioma-stem-like-cells-through-the-downregulation-of-notch1
#5
Hai-Bin Feng, Jing Wang, Hao-Ran Jiang, Xin Mei, Yi-Ying Zhao, Fu-Rong Chen, Yue Qu, Ke Sai, Cheng-Cheng Guo, Qun-Ying Yang, Zong-Ping Zhang, Zhong-Ping Chen
Glioma is the most frequent primary central nervous system tumor. Although the current first-line medicine, temozolomide (TMZ), promotes patient survival, drug resistance develops easily. Thus, it is important to investigate novel therapeutic reagents to solidify the treatment effect. β-Elemene (bELE) is a compound from a Chinese herb whose anticancer effect has been shown in various types of cancer. However, its role in the inhibition of glioma stem-like cells (GSLCs) has not yet been reported. We studied both the in vitro and the in vivo inhibitory effect of bELE and TMZ in GSLCs and parental cells and their combined effects...
March 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28241798/leveraging-the-ehr4cr-platform-to-support-patient-inclusion-in-academic-studies-challenges-and-lessons-learned
#6
Yannick Girardeau, Justin Doods, Eric Zapletal, Gilles Chatellier, Christel Daniel, Anita Burgun, Martin Dugas, Bastien Rance
BACKGROUND: The development of Electronic Health Records (EHRs) in hospitals offers the ability to reuse data from patient care activities for clinical research. EHR4CR is a European public-private partnership aiming to develop a computerized platform that enables the re-use of data collected from EHRs over its network. However, the reproducibility of queries may depend on attributes of the local data. Our objective was 1/ to describe the different steps that were achieved in order to use the EHR4CR platform and 2/ to identify the specific issues that could impact the final performance of the platform...
February 28, 2017: BMC Medical Research Methodology
https://www.readbyqxmd.com/read/28198106/in-vitro-microfluidic-models-of-tumor-microenvironment-to-screen-transport-of-drugs-and-nanoparticles
#7
REVIEW
Altug Ozcelikkale, Hye-Ran Moon, Michael Linnes, Bumsoo Han
Advances in nanotechnology have enabled numerous types of nanoparticles (NPs) to improve drug delivery to tumors. While many NP systems have been proposed, their clinical translation has been less than anticipated primarily due to failure of current preclinical evaluation techniques to adequately model the complex interactions between the NP and physiological barriers of tumor microenvironment. This review focuses on microfluidic tumor models for characterization of delivery efficacy and toxicity of cancer nanomedicine...
February 14, 2017: Wiley Interdisciplinary Reviews. Nanomedicine and Nanobiotechnology
https://www.readbyqxmd.com/read/28197542/the-proline-arginine-dipeptide-from-hexanucleotide-repeat-expanded-c9orf72-inhibits-the-proteasome
#8
Rahul Gupta, Matthews Lan, Jelena Mojsilovic-Petrovic, Won Hoon Choi, Nathaniel Safren, Sami Barmada, Min Jae Lee, Robert Kalb
An intronic hexanucleotide repeat expansion (HRE) mutation in the C9ORF72 gene is the most common cause of familial ALS and frontotemporal dementia (FTD) and is found in ∼7% of individuals with apparently sporadic disease. Several different diamino acid peptides can be generated from the HRE by noncanonical translation (repeat-associated non-ATG translation, or RAN translation), and some of these peptides can be toxic. Here, we studied the effects of two arginine containing RAN translation products [proline/arginine repeated 20 times (PR20) and glycine/arginine repeated 20 times (GR20)] in primary rat spinal cord neuron cultures grown on an astrocyte feeder layer...
January 2017: ENeuro
https://www.readbyqxmd.com/read/28196472/premeta-a-tool-to-facilitate-meta-analysis-of-rare-variant-associations
#9
Zheng-Zheng Tang, Paul Bunn, Ran Tao, Zhouwen Liu, Dan-Yu Lin
BACKGROUND: Meta-analysis is essential to the discovery of rare variants that influence complex diseases and traits. Four major software packages, namely MASS, MetaSKAT, RAREMETAL, and seqMeta, have been developed to perform meta-analysis of rare-variant associations. These packages first generate summary statistics for each study and then perform the meta-analysis by combining the summary statistics. Because of incompatible file formats and non-equivalent summary statistics, the output files from the study-level analysis of one package cannot be directly used to perform meta-analysis in another package...
February 14, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28179980/increasing-european-support-for-neglected-infectious-disease-research
#10
REVIEW
Ole F Olesen, Marit Ackermann
Neglected infectious diseases (NIDs) are a persistent cause of death and disability in low-income countries. Currently available drugs and vaccines are often ineffective, costly or associated with severe side-effects. Although the scale of research on NIDs does not reflect their disease burden, there are encouraging signs that NIDs have begun to attract more political and public attention, which have translated into greater awareness and increased investments in NID research by both public and private donors...
2017: Computational and Structural Biotechnology Journal
https://www.readbyqxmd.com/read/28173837/insulin-like-growth-factor-1-receptor-activation-promotes-mammary-gland-tumor-development-by-increasing-glycolysis-and-promoting-biomass-production
#11
Bas Ter Braak, Christine L Siezen, Joo S Lee, Pooja Rao, Charlotte Voorhoeve, Eytan Ruppin, Jan Willem van der Laan, Bob van de Water
BACKGROUND: The insulin-like growth factor 1 (IGF1) signaling axis plays a major role in tumorigenesis. In a previous experiment, we chronically treated mice with several agonists of the IGF1 receptor (IGF1R). We found that chronic treatment with insulin analogues with high affinity towards the IGF1R (IGF1 and X10) decreased the mammary gland tumor latency time in a p53(R270H/+)WAPCre mouse model. Frequent injections with insulin analogues that only mildly activated the IGF1R in vivo (glargine and insulin) did not significantly decrease the tumor latency time in this mouse model...
February 7, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28167899/cysteine-modifications-in-the-pathogenesis-of-als
#12
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/28108609/visualization-and-quantification-of-browning-using-a-ucp1-2a-luciferase-knock-in-mouse-model
#13
Liufeng Mao, Baoming Nie, Tao Nie, Xiaoyan Hui, Xuefei Gao, Xiaoliang Lin, Xin Liu, Yong Xu, Xiaofeng Tang, Ran Yuan, Kuai Li, Peng Li, Ke Ding, Yu Wang, Aimin Xu, Jian Fei, Weiping Han, Pentao Liu, Lise Madsen, Karsten Kristiansen, Zhiguang Zhou, Sheng Ding, Donghai Wu
Both mammals and adult humans possess classic brown adipocytes and beige adipocytes, and the amount and activity of these adipocytes are considered key factors in combating obesity and its associated metabolic diseases. Uncoupling protein 1 (Ucp1) is the functional marker of both brown and beige adipocytes. To facilitate a reliable, easy, and sensitive measurement of Ucp1 expression both in vivo and in vitro, we generated a Ucp1-2A-luciferase knock-in mouse by deleting the stop codon for the mouse Ucp1 gene and replacing it with a 2A peptide...
February 2017: Diabetes
https://www.readbyqxmd.com/read/28099324/interaction-of-isoflurane-tumor-necrosis-factor-%C3%AE-and-%C3%AE-amyloid-on-long-term-potentiation-in-rat-hippocampal-slices
#14
Ran Zhou, Philip Bickler
BACKGROUND: The relationship between inhalational anesthetics such as isoflurane and cognitive impairment in the elderly is controversial. Both β-amyloid peptide (Aβ), associated with Alzheimer disease, and tumor necrosis factor-α (TNF-α), a proinflammatory stress-related peptide, impair the synaptic function. We hypothesized that transient exposure to isoflurane and these peptides would impair synaptic function, manifest as a depression of long-term potentiation (LTP) and paired pulse facilitation (PPF), in the rat hippocampus...
February 2017: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/28088213/glycine-alanine-dipeptide-repeat-protein-contributes-to-toxicity-in-a-zebrafish-model-of-c9orf72-associated-neurodegeneration
#15
Yu Ohki, Andrea Wenninger-Weinzierl, Alexander Hruscha, Kazuhide Asakawa, Koichi Kawakami, Christian Haass, Dieter Edbauer, Bettina Schmid
BACKGROUND: The most frequent genetic cause of frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) is the expansion of a GGGGCC hexanucleotide repeat in a non-coding region of the chromosome 9 open reading frame 72 (C9orf72) locus. The pathological hallmarks observed in C9orf72 repeat expansion carriers are the formation of RNA foci and deposition of dipeptide repeat (DPR) proteins derived from repeat associated non-ATG (RAN) translation. Currently, it is unclear whether formation of RNA foci, DPR translation products, or partial loss of C9orf72 predominantly drive neurotoxicity in vivo...
January 14, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28055140/eif2s3-mutations-associated-with-severe-x-linked-intellectual-disability-syndrome-mehmo
#16
Martina Skopkova, Friederike Hennig, Byung-Sik Shin, Clesson E Turner, Daniela Stanikova, Katarina Brennerova, Juraj Stanik, Ute Fischer, Lyndal Henden, Ulrich Müller, Daniela Steinberger, Esther Leshinsky-Silver, Armand Bottani, Timea Kurdiova, Jozef Ukropec, Olga Nyitrayova, Miriam Kolnikova, Iwar Klimes, Guntram Borck, Melanie Bahlo, Stefan A Haas, Joo-Ran Kim, Leda E Lotspeich-Cole, Daniela Gasperikova, Thomas E Dever, Vera M Kalscheuer
Impairment of translation initiation and its regulation within the integrated stress response (ISR) and related unfolded-protein response has been identified as a cause of several multisystemic syndromes. Here, we link MEHMO syndrome, whose genetic etiology was unknown, to this group of disorders. MEHMO is a rare X-linked syndrome characterized by profound intellectual disability, epilepsy, hypogonadism and hypogenitalism, microcephaly, and obesity. We have identified a C-terminal frameshift mutation (Ile465Serfs) in the EIF2S3 gene in three families with MEHMO syndrome and a novel maternally inherited missense EIF2S3 variant (c...
April 2017: Human Mutation
https://www.readbyqxmd.com/read/28031329/hur-enhances-early-restitution-of-the-intestinal-epithelium-by-increasing-cdc42-translation
#17
Lan Liu, Ran Zhuang, Lan Xiao, Hee Kyoung Chung, Jason Luo, Douglas J Turner, Jaladanki N Rao, Myriam Gorospe, Jian-Ying Wang
The mammalian intestinal mucosa exhibits a spectrum of responses after acute injury and repairs itself rapidly to restore the epithelial integrity. The RNA-binding protein HuR regulates the stability and translation of target mRNAs and is involved in many aspects of gut epithelium homeostasis, but its exact role in the regulation of mucosal repair after injury remains unknown. Here we show that HuR is essential for early intestinal epithelial restitution by increasing the expression of cell division control protein 42 (Cdc42) at the posttranscriptional level...
December 28, 2016: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28024311/lost-in-translation-the-search-for-an-in-vitro-screen-for-spermatogenic-toxicity
#18
Robert E Chapin, Timothy Winton, William Nowland, Nichole Danis, Steven Kumpf, Kjell Johnson, Aleasha Coburn, Jan-Bernd Stukenborg
The last two decades have seen an increasing search for in vitro models that can replace the use of animals for safety testing. We adapted the methods from a recent nonquantitative report of spermatogenesis occurring in ex vivo mouse testis explants and tried to develop them into a screening assay. The model consisted of small pieces of neonatal mouse testis (testis "chunks"), explanted and placed on pillars of agarose or chamber inserts, and cultured at the air-liquid interface. A peripheral torus-shaped zone in these explants would often contain tubules showing spermatogenesis, while the middle of each chunk was often necrotic, depending on the thickness of the tissue...
December 2016: Birth Defects Research. Part B, Developmental and Reproductive Toxicology
https://www.readbyqxmd.com/read/28013268/rna-g-quadruplexes-emerging-mechanisms-in-disease
#19
Anne Cammas, Stefania Millevoi
RNA G-quadruplexes (G4s) are formed by G-rich RNA sequences in protein-coding (mRNA) and non-coding (ncRNA) transcripts that fold into a four-stranded conformation. Experimental studies and bioinformatic predictions support the view that these structures are involved in different cellular functions associated to both DNA processes (telomere elongation, recombination and transcription) and RNA post-transcriptional mechanisms (including pre-mRNA processing, mRNA turnover, targeting and translation). An increasing number of different diseases have been associated with the inappropriate regulation of RNA G4s exemplifying the potential importance of these structures on human health...
December 23, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/28007939/single-synonymous-mutation-in-factor-ix-alters-protein-properties-and-underlies-haemophilia-b
#20
Vijaya L Simhadri, Nobuko Hamasaki-Katagiri, Brian C Lin, Ryan Hunt, Sujata Jha, Sandra C Tseng, Andrew Wu, Amber A Bentley, Ran Zichel, Qi Lu, Lily Zhu, Darón I Freedberg, Dougald M Monroe, Zuben E Sauna, Robert Peters, Anton A Komar, Chava Kimchi-Sarfaty
BACKGROUND: Haemophilia B is caused by genetic aberrations in the F9 gene. The majority of these are non-synonymous mutations that alter the primary structure of blood coagulation factor IX (FIX). However, a synonymous mutation c.459G>A (Val107Val) was clinically reported to result in mild haemophilia B (FIX coagulant activity 15%-20% of normal). The F9 mRNA of these patients showed no skipping or retention of introns and/or change in mRNA levels, suggesting that mRNA integrity does not contribute to the origin of the disease in affected individuals...
December 22, 2016: Journal of Medical Genetics
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