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RAN translation

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
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...
October 19, 2016: Annals of Neurology
Thomas Westergard, Brigid K Jensen, Xinmei Wen, Jingli Cai, Elizabeth Kropf, Lorraine Iacovitti, Piera Pasinelli, Davide Trotti
Aberrant hexanucleotide repeat expansions in C9orf72 are the most common genetic change underlying amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). RNA transcripts containing these expansions undergo repeat-associated non-ATG translation (RAN-T) to form five dipeptide repeat proteins (DPRs). DPRs are found as aggregates throughout the CNS of C9orf72-ALS/FTD patients, and some cause degeneration when expressed in vitro in neuronal cultures and in vivo in animal models. The spread of characteristic disease-related proteins drives the progression of pathology in many neurodegenerative diseases...
October 11, 2016: Cell Reports
Rui Ran, Anton P J Middelberg, Chun-Xia Zhao
Nanotechnology has started a new era in engineering multifunctional nanoparticles for diagnosis and therapeutics by incorporating therapeutic drugs, targeting ligands, stimuli-responsive release and imaging molecules. However, more functionality requires more complex synthesis processes, resulting in poor reproducibility, low yield and high production cost, hence difficulties in clinical translation. Herein we report a one-step microfluidic method for making multifunctional liposomes. Three formulations were prepared using this simple method, including plain liposomes, PEGylated liposomes and folic acid functionalised liposomes, all with a fluorescence dye encapsulated for imaging...
September 12, 2016: Colloids and Surfaces. B, Biointerfaces
Luis Huicho, Carlos A Huayanay-Espinoza, Eder Herrera-Perez, Jessica Niño de Guzman, Maria Rivera-Ch, Maria Clara Restrepo-Méndez, Aluisio J D Barros
BACKGROUND: Peru has impressively reduced its neonatal mortality rate (NMR). We aimed, for the period 2000-2013, to: (a) describe national and district NMR variations over time; (b) assess NMR trends by wealth quintile and place of residence; (c) describe evolution of mortality causes; (d) assess completeness of registered mortality; (e) assess coverage and equity of NMR-related interventions; and (f) explore underlying driving factors. METHODS: We compared national NMR time trends from different sources...
2016: BMC Public Health
Caiyan Wang, Qian Jia, Ran Chen, Yuming Wei, Juntao Li, Jie Ma, Wei Xie
tRNA methyltransferase Trm5 catalyses the transfer of a methyl group from S-adenosyl-L-methionine to G37 in eukaryotes and archaea. The N1-methylated guanosine is the product of the initial step of the wyosine hypermodification, which is essential for the maintenance of the reading frame during translation. As a unique member of this enzyme family, Trm5a from Pyrococcus abyssi (PaTrm5a) catalyses not only the methylation of N1, but also the further methylation of C7 on 4-demethylwyosine at position 37 to produce isowyosine, but the mechanism for the double methylation is poorly understood...
2016: Scientific Reports
Xinmei Wen, Thomas Westergard, Piera Pasinelli, Davide Trotti
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are two apparently distinct neurodegenerative diseases, the former characterized by selective loss of motor neurons in the brain and spinal cord and the latter characterized by selective atrophy of frontal and temporal lobes. Over the years, however, growing evidence from clinical, pathological and genetic findings has suggested that ALS and FTD belong to the same clinic-pathological spectrum disorder. This concept has been further supported by the identification of the most common genetic cause for both diseases, an aberrantly expanded hexanucleotide repeat GGGGCC/ CCCCGG sequence located in a non-coding region of the gene C9orf72...
September 13, 2016: Neuroscience Letters
Jennifer E Cohen, Claire E Wakefield, Richard J Cohn
BACKGROUND: Childhood cancer survivors are at a higher risk of developing health conditions such as osteoporosis, and cardiovascular disease than their peers. Health-promoting behaviour, such as consuming a healthy diet, could lessen the impact of these chronic issues, yet the prevalence rate of health-protecting behaviour amongst survivors of childhood cancer is similar to that of the general population. Targeted nutritional interventions may prevent or reduce the incidence of these chronic diseases...
2016: Cochrane Database of Systematic Reviews
Jennifer M Weller, David Cumin, Ian D Civil, Jane Torrie, Alexander Garden, Andrew D MacCormick, Nishanthi Gurusinghe, Matthew J Boyd, Christopher Frampton, Martina Cokorilo, Magnus Tranvik, Lisa Carlsson, Tracey Lee, Wai Leap Ng, Michael Crossan, Alan F Merry
AIMS: We ran a Multidisciplinary Operating Room Simulation (MORSim) course for 20 complete general surgical teams from two large metropolitan hospitals. Our goal was to improve teamwork and communication in the operating room (OR). We hypothesised that scores for teamwork and communication in the OR would improve back in the workplace following MORSim. We used an extended Behavioural Marker Risk Index (BMRI) to measure teamwork and communication, because a relationship has previously been documented between BMRI scores and surgical patient outcomes...
2016: New Zealand Medical Journal
Jan Geweke, Pranav R Shirhatti, Igor Rahinov, Christof Bartels, Alec M Wodtke
In this work we seek to examine the nature of collisional energy transfer between HCl and Au(111) for nonreactive scattering events that sample geometries near the transition state for dissociative adsorption by varying both the vibrational and translational energy of the incident HCl molecules in the range near the dissociation barrier. Specifically, we report absolute vibrational excitation probabilities for HCl(v = 0 → 1) and HCl(v = 1 → 2) scattering from clean Au(111) as a function of surface temperature and incidence translational energy...
August 7, 2016: Journal of Chemical Physics
Zhang Bao, Ran Chen, Pei Zhang, Shan Lu, Xing Chen, Yake Yao, Xiaozheng Jin, Yilan Sun, Jianying Zhou
Mycobacterium tuberculosis (MTB), one of the major bacterial pathogens for lethal infectious diseases, is capable of surviving within the phagosomes of host alveolar macrophages; therefore, host genetic variations may alter the susceptibility to MTB. In this study, to identify host genes exploited by MTB during infection, genes were non-selectively inactivated using lentivirus-based antisense RNA methods in Raw264.7 macrophages, and the cells that survived virulent MTB infection were then screened. Following DNA sequencing of the surviving cell clones, 26 host genes affecting susceptibility to MTB were identified and their pathways were analyzed by bioinformatics analysis...
September 2016: International Journal of Molecular Medicine
Mark Linden, Carol Hawley, Bronagh Blackwood, Jonathan Evans, Vicki Anderson, Conall O'Rourke
BACKGROUND: The use of technology in healthcare settings is on the increase and may represent a cost-effective means of delivering rehabilitation. Reductions in treatment time, and delivery in the home, are also thought to be benefits of this approach. Children and adolescents with brain injury often experience deficits in memory and executive functioning that can negatively affect their school work, social lives, and future occupations. Effective interventions that can be delivered at home, without the need for high-cost clinical involvement, could provide a means to address a current lack of provision...
2016: Cochrane Database of Systematic Reviews
Wouter Hoogkamer, Shalaya Kipp, Barry A Spiering, Rodger Kram
PURPOSE: Our goal was to quantify if small (1 - 3%) changes in running economy quantitatively affect distance-running performance. Based on the linear relationship between metabolic rate and running velocity and on earlier observations that added shoe mass increases metabolic rate by ~1% per 100 grams per shoe, we hypothesized that adding 100 and 300 grams per shoe would slow 3,000m time-trial performance by 1% and 3%, respectively. METHODS: 18 male, sub-20 minute 5km runners completed treadmill testing, and three 3,000m time-trials wearing control shoes and identical shoes with 100 and 300 grams of discreetly added mass...
June 20, 2016: Medicine and Science in Sports and Exercise
José I Urgel, David Écija, Guoqing Lyu, Ran Zhang, Carlos-Andres Palma, Willi Auwärter, Nian Lin, Johannes V Barth
The recognition of quasicrystals, which exhibit long-range order but lack translational symmetry, represented both the introduction of a new class of materials and a transformative breakthrough in crystallography. Concomitant with the exploration of quasicrystallinity, metal-organic architectures emerged as promising and versatile systems with significant application potential. Their building principles have been studied extensively and become manifest in a multitude of intricate amorphous and crystalline phases...
July 2016: Nature Chemistry
Masataka Nakazawa, Akimoto Nimura, Tomoyuki Mochizuki, Masahiro Koizumi, Tatsuo Sato, Keiichi Akita
BACKGROUND: Several biomechanical studies have shown that the acromioclavicular (AC) ligament prevents posterior translation of the clavicle in the horizontal plane. In anatomy textbooks, however, the AC ligament is illustrated as running straight across the AC joint surface. HYPOTHESIS: The AC ligament does not run straight across the joint surface, and the configuration of the AC ligament may vary. STUDY DESIGN: Descriptive laboratory study...
June 17, 2016: American Journal of Sports Medicine
Shi-Ju Ran
In this work, a simple and fundamental numeric scheme dubbed as ab initio optimization principle (AOP) is proposed for the ground states of translational invariant strongly correlated quantum lattice models. The idea is to transform a nondeterministic-polynomial-hard ground-state simulation with infinite degrees of freedom into a single optimization problem of a local function with finite number of physical and ancillary degrees of freedom. This work contributes mainly in the following aspects: (1) AOP provides a simple and efficient scheme to simulate the ground state by solving a local optimization problem...
May 2016: Physical Review. E
Mengmeng Cheng, Shurong Hu, Zhengting Wang, Yaofei Pei, Rong Fan, Xiqiang Liu, Lei Wang, Jie Zhou, Sichang Zheng, Tianyu Zhang, Yun Lin, Maochen Zhang, Ran Tao, Jie Zhong
Neddylation, a newly identified post-translational modification, is significant for the activity and stability of target proteins. The exact role of neddylation in the pathogenesis of inflammatory bowel disease, specifically those mediated by dendritic cells (DCs), was still rarely reported. Here, we showed that inhibition of neddylation protected mice from mucosal inflammation. Targeting neddylation also inhibited DC maturation characterized by reduced cytokine production, down-regulated costimulatory molecules and suppressed capacity in allogeneic T cell stimulation...
May 21, 2016: Oncotarget
Ewan D McNicol, McKenzie C Ferguson, Simon Haroutounian, Daniel B Carr, Roman Schumann
BACKGROUND: This is an updated version of the original Cochrane review published in Issue 10, 2011. Paracetamol (acetaminophen) is the most commonly prescribed analgesic for the treatment of acute pain. It may be administered orally, rectally, or intravenously. The efficacy and safety of intravenous (IV) formulations of paracetamol, IV paracetamol, and IV propacetamol (a prodrug that is metabolized to paracetamol), compared with placebo and other analgesics, is unclear. OBJECTIVES: To assess the efficacy and safety of IV formulations of paracetamol for the treatment of postoperative pain in both adults and children...
2016: Cochrane Database of Systematic Reviews
Fengjun Fang, Ru-Lin Huang, Yongchao Zheng, Ming Liu, Ran Huo
BACKGROUND: Hypertrophic scars and keloids, characterized by over-proliferation of fibroblasts and aberrant formation of the extracellular matrix (ECM), are considered fibrotic diseases. Accumulating evidence indicates that mesenchymal stem cells (MSCs) promote scar-free wound healing and inhibit fibrotic tissue formation, making them a potentially effective therapeutic treatment for hypertrophic scars and keloids. OBJECTIVE: To investigate the paracrine effects of bone marrow derived MSCs (BMSCs) on the biological behavior of hypertrophic scar fibroblasts (HSFs) and keloid fibroblasts (KFs)...
August 2016: Journal of Dermatological Science
Diana C Cox, Thomas A Cooper
Repeat expansions cause dominantly inherited neurological disorders. In this issue of Molecular Cell, Kearse et al. (2016) examine the requirements for RAN translation of the CGG repeats that cause fragile X-associated tremor/ataxia syndrome, revealing similarities and differences with canonical translation.
April 21, 2016: Molecular Cell
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