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https://www.readbyqxmd.com/read/27911187/fxr1a-associated-micrornp-a-driver-of-specialized-non-canonical-translation-in-quiescent-conditions
#1
Syed I A Bukhari, Shobha Vasudevan
Eukaryotic protein synthesis is a multifaceted process that requires coordination of a set of translation factors in a particular cellular state. During normal growth and proliferation, cells generally make their proteome via conventional translation that utilizes canonical translation factors. When faced with environmental stress such as growth factor deprivation, or in response to biological cues such as developmental signals, cells can have stalled canonical translation. In this situation, cells adapt alternative modes of translation to make specific proteins necessary for required biological functions under these distinct conditions...
December 2, 2016: RNA Biology
https://www.readbyqxmd.com/read/27907057/the-effects-of-irreversible-electroporation-on-the-colon-in-a-porcine-model
#2
Xiaomei Luo, Xianjun Liang, Jiannan Li, Jian Shi, Wenlong Zhang, Wei Chai, Jiuping Wu, Shuai Guo, Gang Fang, Xulong Zhou, Jianhua Zhang, Kecheng Xu, Jianying Zeng, Lizhi Niu
BACKGROUND AND AIM: Irreversible electroporation (IRE) is a method of targeted cell ablation which has been suggested as a potential cancer therapy as it leaves structures such as blood vessels and the extracellular matrix intact, thereby allowing the rapid recovery of healthy tissue. Here, we investigated the effects of IRE on the colon in vivo in a porcine model. METHODS: IRE ablation was performed on the colon walls of 12 female Tibet mini-pigs, creating a total of 24 lesions...
2016: PloS One
https://www.readbyqxmd.com/read/27906081/vacht-overexpression-increases-acetylcholine-at-the-synaptic-cleft-and-accelerates-aging-of-neuromuscular-junctions
#3
Satoshi Sugita, Leland L Fleming, Caleb Wood, Sydney K Vaughan, Matheus P S M Gomes, Wallace Camargo, Ligia A Naves, Vania F Prado, Marco A M Prado, Cristina Guatimosim, Gregorio Valdez
BACKGROUND: Cholinergic dysfunction occurs during aging and in a variety of diseases, including amyotrophic lateral sclerosis (ALS). However, it remains unknown whether changes in cholinergic transmission contributes to age- and disease-related degeneration of the motor system. Here we investigated the effect of moderately increasing levels of synaptic acetylcholine (ACh) on the neuromuscular junction (NMJ), muscle fibers, and motor neurons during development and aging and in a mouse model for amyotrophic lateral sclerosis (ALS)...
October 5, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27903483/therapeutic-benefits-and-adverse-effects-of-combined-pro-angiogenic-gene-therapy-in-mouse-critical-leg-ischemia
#4
Benoît Lebas, Julien Galley, Edith Renaud-Gabardos, Françoise Pujol, Françoise Lenfant, Barbara Garmy-Susini, Xavier Chaufour, Anne-Catherine Prats
OBJECTIVE: Critical leg ischemia (CLI) represents the ultimate stage of peripheral arterial disease. Despite current surgery advances, patients with CLI have limited therapeutic options. Therapeutic angiogenesis thus appears as a powerful approach, aiming to stimulate vessel formation by angiogenic molecules administration. In this context, combined gene therapy has proved the most efficient. The present study aims to compare, in a preclinical mouse model, the therapeutic benefit of a combination of two angiogenic factors FGF2 (fibroblast growth factor 2) and Cyr61 using plasmid and viral vectors, able to generate short or long-term transgene expression in the leg, respectively...
November 26, 2016: Annals of Vascular Surgery
https://www.readbyqxmd.com/read/27899653/control-of-the-negative-ires-trans-acting-factor-khsrp-by-ubiquitination
#5
Yu-An Kung, Chuan-Tien Hung, Kun-Yi Chien, Shin-Ru Shih
Cells and viruses can utilize internal ribosome entry sites (IRES) to drive translation when cap-dependent translation is inhibited by stress or viral factors. IRES trans-acting factors (ITAFs) are known to participate in such cap-independent translation, but there are gaps in the understanding as to how ITAFs, particularly negative ITAFs, regulate IRES-driven translation. This study found that Lys109, Lys121 and Lys122 represent critical ubiquitination sites for far upstream element-binding protein 2 (KHSRP, also known as KH-type splicing regulatory protein or FBP2), a negative ITAF...
November 28, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27899592/an-mrna-specific-trnai-carrier-eif2a-plays-a-pivotal-role-in-cell-proliferation-under-stress-conditions-stress-resistant-translation-of-c-src-mrna-is-mediated-by-eif2a
#6
Oh Sung Kwon, Sihyeon An, Eunah Kim, Jinbae Yu, Ka Young Hong, Jae Seung Lee, Sung Key Jang
c-Src, a non-receptor protein tyrosine kinase, activates NF-κB and STAT3, which in turn triggers the transcription of anti-apoptosis- and cell cycle-related genes. c-Src protein regulates cell proliferation, cell motility and programmed cell death. And the elevated level of activated c-Src protein is related with solid tumor generation. Translation of c-Src mRNA is directed by an IRES element which mediates persistent translation under stress conditions when translation of most mRNAs is inhibited by a phosphorylation of the alpha subunit of eIF2 carrying the initiator tRNA (tRNAi) to 40S ribosomal subunit under normal conditions...
November 28, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27893744/optimization-of-irreversible-electroporation-protocols-for-in-vivo-myocardial-decellularization
#7
Yaniv Zager, David Kain, Natalie Landa, Jonathan Leor, Elad Maor
BACKGROUND: Irreversible electroporation (IRE) is a non-thermal cell ablation approach that induces selective damage to cell membranes only. The purpose of the current study was to evaluate and optimize its use for in-vivo myocardial decellularization. METHODS: Forty-two Sprague-Dawley rats were used to compare myocardial damage of seven different IRE protocols with anterior myocardial infarction damage. An in-vivo open thoracotomy model was used, with two-needle electrodes in the anterior ventricular wall...
2016: PloS One
https://www.readbyqxmd.com/read/27892898/the-role-of-adipose-tissue-and-excess-of-fatty-acids-in-the-induction-of-insulin-resistance-in-skeletal-muscle
#8
Agnieszka Błachnio-Zabielska, Sławomir Grycel, Marta Chacińska, Piotr Zabielski
Skeletal muscle is the main tissue responsible for insulin-stimulated glucose uptake. Consumption of a high-fat diet rich in saturated fats (HFD) and obesity are associated with accumulation of intramuscular lipids that leads to several disorders, e.g. insulin resistance (IRes) and type 2 diabetes (T2D). The mechanism underlying the induction of IRes is still unknown. It was speculated that accumulation of intramuscular triacylglycerols (TAG) is linked to induction of IRes. Now, research focuses on bioactive lipids: long-chain acyl-CoA (LCACoA), diacylglycerols (DAG) and ceramides (Cer)...
November 14, 2016: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/27880932/lgr6-stem-cells-and-their-progeny-in-mouse-epidermis-under-regimens-of-exogenous-skin-carcinogenesis-and-their-absence-in-ensuing-skin-tumors
#9
Gerline C van de Glind, Heggert G Rebel, Jacoba J Out-Luiting, Wim Zoutman, Cornelis P Tensen, Frank R de Gruijl
Lgr6+ cells have been identified as a novel class of proliferating (Ki67+) stem cells in mouse epidermis. We investigated their response to UV exposure in Lgr6-EGFP-Ires-CreERT2/R26R-LacZ haired and hairless mice and whether they become initiating cells of UV- or chemically induced skin tumors. UV overexposure erased Lgr6+ cells (EGFP+) from the interfollicular epidermis (IFE), but - as after wounding - they apparently repopulated the IFE from the hair follicles. Under sub-sunburn chronic UV exposure, Lgr6+ cells and their progeny (LacZ+ after pulse of tamoxifen) diminished strongly in the IFE...
November 17, 2016: Oncotarget
https://www.readbyqxmd.com/read/27877903/the-novel-functional-nucleic-acid-ired-effectively-regulates-target-genes-following-cytoplasmic-delivery-by-faint-electric-treatment
#10
Mahadi Hasan, Noriko Tarashima, Koki Fujikawa, Takashi Ohgita, Susumu Hama, Tamotsu Tanaka, Hiroyuki Saito, Noriaki Minakawa, Kentaro Kogure
An intelligent shRNA expression device (iRed) contains the minimum essential components needed for shRNA production in cells, and could be a novel tool to regulate target genes. However, general delivery carriers consisting of cationic polymers/lipids could impede function of a newly generated shRNA via electrostatic interaction in the cytoplasm. Recently, we found that faint electric treatment (fET) of cells enhanced delivery of siRNA and functional nucleic acids into the cytoplasm in the absence of delivery carriers...
2016: Science and Technology of Advanced Materials
https://www.readbyqxmd.com/read/27875274/sirt1-inhibits-ev71-genome-replication-and-rna-translation-by-interfering-viral-polymerase-and-5-utr-rna
#11
Yang Han, Lvyin Wang, Jin Cui, Yu Song, Zhen Luo, Junbo Chen, Ying Xiong, Qi Zhang, Fang Liu, Wenzhe Ho, Yingle Liu, Kailang Wu, Jianguo Wu
Enterovirus 71 (EV71) possesses a single-stranded positive RNA genome that contains a single open reading frame (ORF) flanked by a 5'untranslated region (5'UTR) and a polyadenylated 3'UTR. Here, we demonstrated that EV71 activates the production of silent mating type information regulation 2 homolog 1 (SIRT1), a histone deacetylase (HDAC). EV71 further stimulates SIRT1 sumoylation and deacetylase activity, and enhances SIRT1 translocation from nuclear to cytoplasm. More interestingly, activated SIRT1 subsequently binds with EV71 3D protein (a viral RNA-dependent RNA polymerase, RdRp) to repress the acetylation and RdRp activity of 3D, resulting in the attenuation of viral genome replication...
November 14, 2016: Journal of Cell Science
https://www.readbyqxmd.com/read/27870918/time-dependent-impact-of-irreversible-electroporation-on-pancreas-liver-blood-vessels-and-nerves-a-systematic-review-of-experimental-studies
#12
J A Vogel, E van Veldhuisen, P Agnass, J Crezee, F Dijk, J Verheij, T M van Gulik, M R Meijerink, L G Vroomen, K P van Lienden, M G Besselink
INTRODUCTION: Irreversible electroporation (IRE) is a novel ablation technique in the treatment of unresectable cancer. The non-thermal mechanism is thought to cause mostly apoptosis compared to necrosis in thermal techniques. Both in experimental and clinical studies, a waiting time between ablation and tissue or imaging analysis to allow for cell death through apoptosis, is often reported. However, the dynamics of the IRE effect over time remain unknown. Therefore, this study aims to summarize these effects in relation to the time between treatment and evaluation...
2016: PloS One
https://www.readbyqxmd.com/read/27863885/cell-type-specific-variation-in-the-induction-of-er-stress-and-downstream-events-in-chikungunya-virus-infection
#13
Sarawut Khongwichit, Nitwara Wikan, Bizunesh Abere, Chutima Thepparit, Atichat Kuadkitkan, Sukathida Ubol, Duncan R Smith
Over the last decade infections with the mosquito transmitted chikungunya virus (CHIKV) have become a major worldwide concern, and considerable efforts have been made in understanding the interaction of this virus with the host cell machinery. Studies have documented the induction of the unfolded protein response (UPR), as well as the induction of apoptosis and autophagy in response to CHIKV infection. This study comparatively analysed these three processes in two cell lines, Hela and HepG2. Infection of Hela cells was characterized by activation of the PERK/eIF2α branch of the UPR, the induction of autophagy and early apoptosis, while infection of HepG2 cells was characterized by activation of the IRE/XBP1 branch of the UPR, limited or no activation of autophagy and comparatively later apoptosis...
November 15, 2016: Microbial Pathogenesis
https://www.readbyqxmd.com/read/27853833/a-researcher-s-guide-to-the-galaxy-of-iress
#14
REVIEW
Ilya M Terenin, Victoria V Smirnova, Dmitri E Andreev, Sergey E Dmitriev, Ivan N Shatsky
The idea of internal initiation is frequently exploited to explain the peculiar translation properties or unusual features of some eukaryotic mRNAs. In this review, we summarize the methods and arguments most commonly used to address cases of translation governed by internal ribosome entry sites (IRESs). Frequent mistakes are revealed. We explain why "cap-independent" does not readily mean "IRES-dependent" and why the presence of a long and highly structured 5' untranslated region (5'UTR) or translation under stress conditions cannot be regarded as an argument for appealing to internal initiation...
November 16, 2016: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/27853311/molecular-analysis-of-the-factorless-internal-ribosome-entry-site-in-cricket-paralysis-virus-infection
#15
Craig H Kerr, Zi Wang Ma, Christopher J Jang, Sunnie R Thompson, Eric Jan
The dicistrovirus Cricket Paralysis virus contains a unique dicistronic RNA genome arrangement, encoding two main open reading frames that are driven by distinct internal ribosome entry sites (IRES). The intergenic region (IGR) IRES adopts an unusual structure that directly recruits the ribosome and drives translation of viral structural proteins in a factor-independent manner. While structural, biochemical, and biophysical approaches have provided mechanistic details into IGR IRES translation, these studies have been limited to in vitro systems and little is known about the behavior of these IRESs during infection...
November 17, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27831561/rapidly-cycling-lgr5-stem-cells-are-exquisitely-sensitive-to-extrinsic-dietary-factors-that-modulate-colon-cancer-risk
#16
Eunjoo Kim, Laurie A Davidson, Roger S Zoh, Martha E Hensel, Michael L Salinas, Bhimanagouda S Patil, Guddadarangavvanahally K Jayaprakasha, Evelyn S Callaway, Clinton D Allred, Nancy D Turner, Brad R Weeks, Robert S Chapkin
The majority of colon tumors are driven by aberrant Wnt signaling in intestinal stem cells, which mediates an efficient route toward initiating intestinal cancer. Natural lipophilic polyphenols and long-chain polyunsaturated fatty acids (PUFAs) generally suppress Wnt- and NF-κB- (nuclear factor-κ light-chain enhancer of activated B-cell) related pathways. However, the effects of these extrinsic agents on colonic leucine-rich repeat-containing G-protein-coupled receptor 5-positive (Lgr5(+)) stem cells, the cells of origin of colon cancer, have not been documented to date...
November 10, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27817015/antitumor-efficacy-of-combined-gene-and-radiotherapy-in-animals
#17
O A Bezborodova, E R Nemtsova, A R Gevorkov, A V Boyko, J B Venediktova, I V Alekseenko, M B Kostina, G S Monastyrskaya, E D Sverdlov, E V Khmelevskiy, R I Yakubovskaya
Antitumor efficacy of the combined suicide gene therapy and radiotherapy was studied on the model of CT26 murine colon adenocarcinoma. CMV-FCU1-IRES-mGM-CSF-pGL3 construct with PEG-PEI-TAT (FCU1-mGM/5-FC) block copolymer as a vector was used for intratumoral administration. Tumors were irradiated with a single 5 Gy dose. The efficacy was evaluated according to the grade of tumor growth inhibition (T/C) and lifespan of the animals. Pronounced antitumor activity of the combined use of FCU1-mGM/5-FC system with radiotherapy on the background of prolonged lifespan and the synergism of the applied methods was revealed...
September 2016: Doklady. Biochemistry and Biophysics
https://www.readbyqxmd.com/read/27816562/over-expression-of-insulin-response-element-binding-protein-1-ire-bp1-in-mouse-pancreatic-islets-increases-expression-of-rack1-and-tctpp-beta-cell-markers-of-high-glucose-sensitivity
#18
Betty C Villafuerte, Michelle T Barati, Madhavi J Rane, Susan Isaacs, Ming Li, Daniel W Wilkey, Michael L Merchant
BACKGROUND: A targeted analysis of the 50kDa C-terminal fragment of insulin-response element binding protein-1 (IRE-BP1) activation of target genes through the insulin receptor substrate receptor/PI-3 kinase/Akt pathway has been demonstrated for the insulin growth factor-1 receptor. The broader effects of 50kDa C-terminal IRE-BP1 fragment over-expression on protein abundance in pancreatic islet beta cells have not been determined. RESULTS: Liquid-chromatography coupled to tandem mass spectrometry (LC-MS/MS) analyses of replicate lysates of pancreatic islets isolated from background strain animals and transgenic animals, overexpressing IRE-BP1 in pancreatic islet beta cells, demonstrated statistically significant increases in the expression of proteins involved in protein synthesis, endoplasmic reticulum (ER) stress and scaffolding proteins important for protein kinase C signaling; some of which were confirmed by immunoblot analyses...
November 3, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27811057/elp3-links-trna-modification-to-ires-dependent-translation-of-lef1-to-sustain-metastasis-in-breast-cancer
#19
Sylvain Delaunay, Francesca Rapino, Lars Tharun, Zhaoli Zhou, Lukas Heukamp, Martin Termathe, Kateryna Shostak, Iva Klevernic, Alexandra Florin, Hadrien Desmecht, Christophe J Desmet, Laurent Nguyen, Sebastian A Leidel, Anne E Willis, Reinhard Büttner, Alain Chariot, Pierre Close
Quantitative and qualitative changes in mRNA translation occur in tumor cells and support cancer progression and metastasis. Posttranscriptional modifications of transfer RNAs (tRNAs) at the wobble uridine 34 (U34) base are highly conserved and contribute to translation fidelity. Here, we show that ELP3 and CTU1/2, partner enzymes in U34 mcm(5)s(2)-tRNA modification, are up-regulated in human breast cancers and sustain metastasis. Elp3 genetic ablation strongly impaired invasion and metastasis formation in the PyMT model of invasive breast cancer...
October 17, 2016: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27797339/endothelial-cation-channel-piezo1-controls-blood-pressure-by-mediating-flow-induced-atp-release
#20
ShengPeng Wang, Ramesh Chennupati, Harmandeep Kaur, Andras Iring, Nina Wettschureck, Stefan Offermanns
Arterial blood pressure is controlled by vasodilatory factors such as nitric oxide (NO) that are released from the endothelium under the influence of fluid shear stress exerted by flowing blood. Flow-induced endothelial release of ATP and subsequent activation of Gq/G11-coupled purinergic P2Y2 receptors have been shown to mediate fluid shear stress-induced stimulation of NO formation. However, the mechanism by which fluid shear stress initiates these processes is unclear. Here, we have shown that the endothelial mechanosensitive cation channel PIEZO1 is required for flow-induced ATP release and subsequent P2Y2/Gq/G11-mediated activation of downstream signaling that results in phosphorylation and activation of AKT and endothelial NOS...
December 1, 2016: Journal of Clinical Investigation
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