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https://www.readbyqxmd.com/read/28198106/in-vitro-microfluidic-models-of-tumor-microenvironment-to-screen-transport-of-drugs-and-nanoparticles
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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 multi-systemic 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...
January 5, 2017: Human Mutation
https://www.readbyqxmd.com/read/28031329/hur-enhances-early-restitution-of-the-intestinal-epithelium-by-increasing-cdc42-translation
#11
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
#12
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
#13
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
#14
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
https://www.readbyqxmd.com/read/27895477/noninvasive-monitoring-of-early-antiangiogenic-therapy-response-in-human-nasopharyngeal-carcinoma-xenograft-model-using-mri-with-rgd-conjugated-ultrasmall-superparamagnetic-iron-oxide-nanoparticles
#15
Yanfen Cui, Caiyuan Zhang, Ran Luo, Huanhuan Liu, Zhongyang Zhang, Tianyong Xu, Yong Zhang, Dengbin Wang
PURPOSE: Arginine-glycine-aspartic acid (RGD)-based nanoprobes allow specific imaging of integrin αvβ3, a protein overexpressed during angiogenesis. Therefore, this study applied a novel RGD-coupled, polyacrylic acid (PAA)-coated ultrasmall superparamagnetic iron oxide (USPIO) (referred to as RGD-PAA-USPIO) in order to detect tumor angiogenesis and assess the early response to antiangiogenic treatment in human nasopharyngeal carcinoma (NPC) xenograft model by magnetic resonance imaging (MRI)...
2016: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/27836902/active-vs-sedentary-lifestyle-from-weaning-to-adulthood-and-susceptibility-to-ozone-in-rats
#16
C J Gordon, P M Phillips, A Ledbetter, S J Snow, M C Schladweiler, A F M Johnstone, U P Kodavanti
The prevalence of a sedentary (SED) life style combined with calorically rich diets has spurred the rise in childhood obesity, which, in turn, translates to adverse health effects in adulthood. Obesity and lack of active (ACT) lifestyle may increase susceptibility to air pollutants. We housed 22-day-old female Long-Evans rats in a cage without (SED) or with a running wheel (ACT). After 10 wk the rats ran 310 ± 16.3 km. Responses of SED and ACT rats to whole-body O3 (0, 0.25, 0.5, or 1.0 ppm; 5 h/day for 2 days) was assessed...
January 1, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/27834869/micrornas-10a-and-10b-regulate-the-expression-of-human-platelet-glycoprotein-ib%C3%AE-for-normal-megakaryopoiesis
#17
Zuping Zhang, Yali Ran, Tanner S Shaw, Yuandong Peng
MicroRNAs are a class of small non-coding RNAs that bind to the three prime untranslated region (3'-UTR) of target mRNAs. They cause a cleavage or an inhibition of the translation of target mRNAs, thus regulating gene expression. Here, we employed three prediction tools to search for potential miRNA target sites in the 3'-UTR of the human platelet glycoprotein (GP) 1BA gene. A luciferase reporter assay shows that miR-10a and -10b sites are functional. When miR-10a or -10b mimics were transfected into the GP Ibβ/GP IX-expressing cells, along with a DNA construct harboring both the coding and 3'-UTR sequences of the human GP1BA gene, we found that they inhibit the transient expression of GP Ibα on the cell surface...
November 9, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27821555/improvement-of-in-vitro-three-dimensional-cartilage-regeneration-by-a-novel-hydrostatic-pressure-bioreactor
#18
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...
November 7, 2016: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/27776165/distinct-c9orf72-associated-dipeptide-repeat-structures-correlate-with-neuronal-toxicity
#19
Brittany N Flores, Mark E Dulchavsky, Amy Krans, Michael R Sawaya, Henry L Paulson, Peter K Todd, Sami J Barmada, Magdalena I Ivanova
Hexanucleotide repeat expansions in C9orf72 are the most common inherited cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The expansions elicit toxicity in part through repeat-associated non-AUG (RAN) translation of the intronic (GGGGCC)n sequence into dipeptide repeat-containing proteins (DPRs). Little is known, however, about the structural characteristics and aggregation propensities of the dipeptide units comprising DPRs. To address this question, we synthesized dipeptide units corresponding to the three sense-strand RAN translation products, analyzed their structures by circular dichroism, electron microscopy and dye binding assays, and assessed their relative toxicity when applied to primary cortical neurons...
2016: PloS One
https://www.readbyqxmd.com/read/27761921/repeat-associated-non-aug-translation-from-antisense-ccg-repeats-in-fragile-x-tremor-ataxia-syndrome
#20
Amy Krans, Michael G Kearse, Peter K Todd
OBJECTIVE: Repeat-associated non-AUG (RAN) translation drives production of toxic proteins from pathogenic repeat sequences in multiple untreatable neurodegenerative disorders. Fragile X-associated tremor/ataxia syndrome (FXTAS) is one such condition, resulting from a CGG trinucleotide repeat expansion in the 5' leader sequence of the FMR1 gene. RAN proteins from the CGG repeat accumulate in ubiquitinated inclusions in FXTAS patient brains and elicit toxicity. In addition to the CGG repeat, an antisense mRNA containing a CCG repeat is also transcribed from the FMR1 locus...
December 2016: Annals of Neurology
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