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A L Baron, A Schoeniger, P Becher, C Baechlein
In recent years, hepatitis C virus (HCV)-related viruses were identified in several species including dogs, horses, bats and rodents. Additionally, a novel virus of the genus Hepacivirus has been discovered in bovine samples and was termed bovine hepacivirus (BovHepV). Prediction of the BovHepV IRES (internal ribosome entry site) structure revealed strong similarities to the HCV IRES structure comprising domains II, IIIabcde, pseudoknot IIIf and domain IV with the initiation codon AUG. Unlike HCV, only one microRNA-122 (miR-122) binding site could be identified in the BovHepV 5' NTR...
May 16, 2018: Journal of Virology
Edward Leen, John Picard, Justin Stebbing, Mark Abel, Tony Dhillon, Harpreet Wasan
Background: The prognosis for unresectable locally advanced pancreatic adenocarcinoma (LAPC) remains poor. There is increasing interest in modern ablative techniques to improve outcomes. We report on the potential value of integrating percutaneous irreversible electroporation (IRE) in patients undergoing systemic chemotherapy. Methods: Seventy-five patients with unresectable pancreatic carcinoma underwent percutaneous IRE after chemotherapy using computerised tomography guidance under general anaesthesia...
April 2018: Journal of Gastrointestinal Oncology
Gregory P Holmes-Hampton, Manik C Ghosh, Tracey A Rouault
Iron regulatory proteins 1 and 2 (IRP1 and IRP2) are two cytosolic proteins that maintain cellular iron homeostasis by regulating the expression of genes involved in iron metabolism. IRPs respond to cellular iron deficiency by binding to iron-responsive elements (IREs) found in the mRNAs of iron metabolism transcripts, enhancing iron import, and reducing iron storage, utilization, and export. IRP1, a bifunctional protein, exists in equilibrium between a [Fe4 S4 ] cluster containing cytosolic aconitase, and an apoprotein that binds to IREs...
2018: Methods in Enzymology
Roman Ganzer, Vinodh Kumar Adithyaa Arthanareeswaran, Hashim U Ahmed, Andrea Cestari, Pascal Rischmann, Georg Salomon, Dogu Teber, Evangelos Liatsikos, Jens-Uwe Stolzenburg, Eric Barret
BACKGROUND: With growing interest in focal therapy (FT) of prostate cancer (PCa) there is an increasing armamentarium of treatment modalities including high-intensity focused ultrasound (HIFU), cryotherapy, focal laser ablation (FLA), irreversible electroporation (IRE), vascular targeted photodynamic therapy (VTP), focal brachytherapy (FBT) and stereotactic ablative radiotherapy (SABR). Currently there are no clear recommendations as to which of these technologies are appropriate for individual patient characteristics...
May 9, 2018: Prostate Cancer and Prostatic Diseases
Václav Vopálenský, Anas Khawaja, Luděk Rožnovský, Jakub Mrázek, Tomáš Mašek, Martin Pospíšek
Hepatitis C virus (HCV) is a single-stranded positive-sense RNA virus from the genus Hepacivirus . The viral genomic +RNA is 9.6 kb long and contains highly structured 5' and 3' untranslated regions (UTRs) and codes for a single large polyprotein, which is co- and post-translationally processed by viral and cellular proteases into at least 11 different polypeptides. Most of the 5' UTR and an initial part of the polyprotein gene are occupied by an internal ribosome entry site (IRES), which mediates cap-independent translation of the viral proteins and allows the virus to overcome cellular antiviral defense based on the overall reduction of the cap-dependent translation initiation...
2018: Frontiers in Microbiology
Piotr Zabielski, Hady Razak Hady, Marta Chacinska, Kamila Roszczyc, Jan Gorski, Agnieszka U Blachnio-Zabielska
We sought to determine whether metformin treatment reverses a high-fat diet (HFD)-induced hepatic insulin resistance (IRes) and to identify lipid intermediates involved in induction of liver IRes. The experiments were conducted on male Wistar rats divided into three groups: 1. Control, 2. fed HFD and 3. fed HFD and treated with metformin. The animals were infused with a [U-13 C]palmitate to measure fractional lipid synthesis rate. This allowed for the calculation of fractional synthesis rate of signaling lipids (FSR) through the estimation of their isotopic enrichment...
May 8, 2018: Scientific Reports
Brian Owens
No abstract text is available yet for this article.
May 7, 2018: CMAJ: Canadian Medical Association Journal, Journal de L'Association Medicale Canadienne
Maike Lenz, Silvia Fademrecht, Mahima Sharma, Jürgen Pleiss, Gideon Grogan, Bettina M Nestl
We report the exploration of the evolutionary relationship between imine reductases (IREDs) and other dehydrogenases. This approach is informed by the sequence similarity between these enzyme families and the recently described promiscuous activity of IREDs for the highly reactive carbonyl compound 2,2,2-trifluoroacetophenone. Using the structure of the R-selective IRED from Streptosporangium roseum (R-IRED-Sr) as a model, β-hydroxyacid dehydrogenases (βHADs) were identified as the dehydrogenases most similar to IREDs...
May 3, 2018: Protein Engineering, Design & Selection: PEDS
Michael Camp
The experimental Clinch River breeder reactor, approved by the U.S. Congress in 1970 for construction in East Tennessee, would have used plutonium instead of uranium. The project drew the ire of environmentalists who insisted that plutonium was too dangerous for commercial use, along with opponents of nuclear proliferation. Tennessee's representatives in Congress, however, desired the jobs that the project would create, and formed legislative coalitions to ensure continued appropriations for the project. Funding lasted until 1983, when fiscal conservatives, concerned about ballooning cost projections, joined with environmentalists to defund the breeder...
2018: Technology and Culture
Erfath Thanjeem Begum M, Dwaipayan Sen
The pathophysiology of Parkinson's disease exhibit imperative roles in unfolded protein response stress-induced oxidative stress and inflammation in general. Although, delta opioid receptor (DOR), has been found to represent anti-parkinsonian effect at behavioral level, its underlying mechanism remains elusive till date. In the present study the role of DOR agonist, SNC-80 and the consorted molecular mechanisms, which translates to behavioral recuperation, has been delineated. In order to mimic PD, mice were intra-peritoneally injected with MPTP, following exposure to SNC-80 and L-DOPA to elucidate amelioration of the MPTP-induced behavioral impairments...
May 1, 2018: Neuroscience Letters
Fenghua Lu, Chan Luo, Nan Li, Qingyou Liu, Yingming Wei, Haiying Deng, Xiaoli Wang, Xiangping Li, Jianrong Jiang, Yanfei Deng, Deshun Shi
The possibility of producing transgenic cloned buffalos by nuclear transfer of fetal fibroblasts expressing enhanced green fluorescent protein (EGFP) was explored in this study. When buffalo fetal fibroblasts (BFFs) isolated from a male buffalo fetus were transfected with pEGFP-N1 (EGFP is driven by CMV and Neo is driven by SV-40) by means of electroporation, Lipofectamine-LTX and X-tremeGENE, the transfection efficiency of electroporation (35.5%) was higher than Lipofectamine-LTX (11.7%) and X-tremeGENE (25...
May 3, 2018: Scientific Reports
Amel Badawi, Abhiruchi Biyanee, Usman Nasrullah, Sofia Winslow, Tobias Schmid, Josef Pfeilschifter, Wolfgang Eberhardt
HuR plays an important role in tumor cell survival mainly through posttranscriptional upregulation of prominent anti-apoptotic genes. In addition, HuR can inhibit the translation of pro-apoptotic factors as we could previously report for caspase-2. Here, we investigated the mechanisms of caspase-2 suppression by HuR and its contribution to chemotherapeutic drug resistance of colon carcinoma cells. In accordance with the significant drug-induced increase in cytoplasmic HuR abundance, doxorubicin and paclitaxel increased the interaction of cytoplasmic HuR with the 5'untranslated region (5'UTR) of caspase-2 as shown by RNA pull down assay...
April 6, 2018: Oncotarget
Alan R Mardinly, Ian Antón Oldenburg, Nicolas C Pégard, Savitha Sridharan, Evan H Lyall, Kirill Chesnov, Stephen G Brohawn, Laura Waller, Hillel Adesnik
Understanding brain function requires technologies that can control the activity of large populations of neurons with high fidelity in space and time. We developed a multiphoton holographic approach to activate or suppress the activity of ensembles of cortical neurons with cellular resolution and sub-millisecond precision. Since existing opsins were inadequate, we engineered new soma-targeted (ST) optogenetic tools, ST-ChroME and IRES-ST-eGtACR1, optimized for multiphoton activation and suppression. Employing a three-dimensional all-optical read-write interface, we demonstrate the ability to simultaneously photostimulate up to 50 neurons distributed in three dimensions in a 550 × 550 × 100-µm3 volume of brain tissue...
April 30, 2018: Nature Neuroscience
S Begum, A Yiu, J Stebbing, L Castellano
The previously unchartered gene expression territory governed by circular RNAs is becoming clearer with the onset of deeper sequencing technologies. The translation of circular RNAs remained a controversial theory until earlier this year, when two studies [1, 2] showed endogenous circular RNA translation in vitro and in vivo, and have further provided mechanistical evidence. In this edition of Oncogene, Zhang et al., provide evidence for the first circular RNA translated with relevance to cancer; a novel tumour suppressor protein, SHPRH-146aa, produced by circ-SHPRH driven by IRES elements...
April 30, 2018: Oncogene
Yu-Rong Chai, Meng-Meng Ge, Ting-Ting Wei, Yan-Long Jia, Xiao Guo, Tian-Yun Wang
Chinese hamster ovary (CHO) cells are mainly used for recombinant protein production. However, the unstable transgene expression and lower transgene copy numbers are the major issues need to be resolved. Here, eleven internal ribosome entry site (IRES) elements from viral and cellular IRES were evaluated for foreign gene expression in CHO-S cells. We constructed eleven fusing plasmids containing different IRES sequences downstream of the enhanced green fluorescent protein (EGFP) gene. EGFP expression was detected by flow cytometry and the transgene copy number was evaluated by quantitative PCR...
April 27, 2018: Scientific Reports
Junko Ogawa, Gerald M Pao, Maxim N Shokhirev, Inder M Verma
We have developed a cancer model of gliomas in human cerebral organoids that allows direct observation of tumor initiation as well as continuous microscopic observations. We used CRISPR/Cas9 technology to target an HRasG12V -IRES-tdTomato construct by homologous recombination into the TP53 locus. Results show that transformed cells rapidly become invasive and destroy surrounding organoid structures, overwhelming the entire organoid. Tumor cells in the organoids can be orthotopically xenografted into immunodeficient NOD/SCID IL2RG-/- animals, exhibiting an invasive phenotype...
April 24, 2018: Cell Reports
Yongji Yang, Michael A J Moser, Edwin Zhang, Wenjun Zhang, Bing Zhang
PURPOSE: The aim of this study was to develop a statistical model for cell death by irreversible electroporation (IRE) and to show that the statistic model is more accurate than the electric field threshold model in the literature using cervical cancer cells in vitro. METHODS: HeLa cell line was cultured and treated with different IRE protocols in order to obtain data for modeling the statistical relationship between the cell death and pulse-setting parameters. In total, 340 in vitro experiments were performed with a commercial IRE pulse system, including a pulse generator and an electric cuvette...
2018: PloS One
Alette H Ruarus, Laurien G P H Vroomen, Robbert S Puijk, Hester J Scheffer, Theo J C Faes, Martijn R Meijerink
PURPOSE: Irreversible electroporation (IRE) induces apoptosis with high-voltage electric pulses. Although the working mechanism is non-thermal, development of secondary Joule heating occurs. This study investigated whether the observed conductivity rise during IRE is caused by increased cellular permeabilization or heat development. METHODS: IRE was performed in a gelatin tissue phantom, in potato tubers, and in 30 patients with unresectable colorectal liver metastases (CRLM)...
April 23, 2018: Cardiovascular and Interventional Radiology
Thibault Datry, Andrew J Boulton, Núria Bonada, Ken Fritz, Catherine Leigh, Eric Sauquet, Klement Tockner, Bernard Hugueny, Clifford N Dahm
Intermittent rivers and ephemeral streams (IRES) are watercourses that cease flow at some point in time and space. Arguably Earth's most widespread type of flowing water, IRES are expanding where Anthropocenic climates grow drier and human demands for water escalate.However, IRES have attracted far less research than perennial rivers and are undervalued by society, jeopardizing their restoration or protection. Provision of ecosystem services by IRES is especially poorly understood, hindering their integration into management plans in most countries...
2018: Journal of Applied Ecology
Maya Korem, Nahum S Goldberg, Amos Cahan, Matan J Cohen, Isaac Nissenbaum, Allon E Moses
Irreversible electroporation (IRE) damages cell membranes and is used in medicine for non-thermal ablation of malignant tumors. Our aim was to evaluate the antimicrobial effect of IRE. The pathogenic microorganisms, S. aureus, S. pyogenes, E. coli, P. aeruginosa and C. albicans were subjected to IRE. Survival was measured as a function of voltage and the number of pulses applied. Combined use of IRE and oxacillin for eradication of S. aureus was also tested. Log10 reduction of microorganisms positively correlated with the number of applied pulses...
April 21, 2018: Letters in Applied Microbiology
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