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https://www.readbyqxmd.com/read/28319090/a-single-copy-sleeping-beauty-transposon-mutagenesis-screen-identifies-new-pten-cooperating-tumor-suppressor-genes
#1
Jorge de la Rosa, Julia Weber, Mathias Josef Friedrich, Yilong Li, Lena Rad, Hannes Ponstingl, Qi Liang, Sandra Bernaldo de Quirós, Imran Noorani, Emmanouil Metzakopian, Alexander Strong, Meng Amy Li, Aurora Astudillo, María Teresa Fernández-García, María Soledad Fernández-García, Gary J Hoffman, Rocío Fuente, George S Vassiliou, Roland Rad, Carlos López-Otín, Allan Bradley, Juan Cadiñanos
The overwhelming number of genetic alterations identified through cancer genome sequencing requires complementary approaches to interpret their significance and interactions. Here we developed a novel whole-body insertional mutagenesis screen in mice, which was designed for the discovery of Pten-cooperating tumor suppressors. Toward this aim, we coupled mobilization of a single-copy inactivating Sleeping Beauty transposon to Pten disruption within the same genome. The analysis of 278 transposition-induced prostate, breast and skin tumors detected tissue-specific and shared data sets of known and candidate genes involved in cancer...
March 20, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28301581/assessing-tn5-and-sleeping-beauty-for-transpositional-transgenesis-by-cytoplasmic-injection-into-bovine-and-ovine-zygotes
#2
R J Bevacqua, R Fernandez-Martin, N G Canel, A Gibbons, D Texeira, F Lange, G Vans Landschoot, V Savy, O Briski, M I Hiriart, E Grueso, Z Ivics, O Taboga, W A Kues, S Ferraris, D F Salamone
Transgenic domestic animals represent an alternative to bioreactors for large-scale production of biopharmaceuticals and could also provide more accurate biomedical models than rodents. However, their generation remains inefficient. Recently, DNA transposons allowed improved transgenesis efficiencies in mice and pigs. In this work, Tn5 and Sleeping Beauty (SB) transposon systems were evaluated for transgenesis by simple cytoplasmic injection in livestock zygotes. In the case of Tn5, the transposome complex of transposon nucleic acid and Tn5 protein was injected...
2017: PloS One
https://www.readbyqxmd.com/read/28295539/a-bibliometric-analysis-of-the-journal-of-advanced-nursing-1976-2015
#3
Danica Železnik, Helena Blažun Vošner, Peter Kokol
BACKGROUND: Bibliometric studies of single journals have been performed, but to the best of our knowledge, bibliometric analysis and bibliometric mapping have not yet been used to analyse the literature production of the Journal of Advanced Nursing. AIM: The aim of this study was to examine the publication characteristics and development of Journal of Advanced Nursing during its 40-year history. DESIGN/METHOD: Using descriptive bibliometrics, we studied the dynamics and trend patterns of literature production and identified document types and the most prolific authors, papers, institutions and countries...
March 15, 2017: Journal of Advanced Nursing
https://www.readbyqxmd.com/read/28284560/computational-discovery-of-niclosamide-ethanolamine-a-repurposed-drug-candidate-that-reduces-growth-of-hepatocellular-carcinoma-cells-in-vitro-and-in-mice-by-inhibiting-cdc37-signaling
#4
Bin Chen, Wei Wei, Li Ma, Bin Yang, Ryan M Gill, Mei-Sze Chua, Atul J Butte, Samuel So
BACKGROUND & AIMS: Drug repositioning offers a shorter approval process than new drug development. We therefore searched large public datasets of drug-induced gene expression signatures to identify agents that might be effective against hepatocellular carcinoma (HCC). METHODS: We searched public databases of mRNA expression patterns reported from HCC specimens from patients, HCC cell lines, and cells exposed to various drugs. We identified drugs that might specifically increase expression of genes that are downregulated in HCCs and reduce expression of genes upregulated in HCCs using a non-parametric, rank-based pattern-matching strategy based on the Kolmogorov-Smirnov statistic...
March 8, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28273073/src-2-mediated-coactivation-of-anti-tumorigenic-target-genes-suppresses-myc-induced-liver-cancer
#5
Shruthy Suresh, Deniz Durakoglugil, Xiaorong Zhou, Bokai Zhu, Sarah Comerford, Chao Xing, Xian-Jin Xie, Brian York, Kathryn A O'Donnell
Hepatocellular carcinoma (HCC) is the fifth most common solid tumor in the world and the third leading cause of cancer-associated deaths. A Sleeping Beauty-mediated transposon mutagenesis screen previously identified mutations that cooperate with MYC to accelerate liver tumorigenesis. This revealed a tumor suppressor role for Steroid Receptor Coactivator 2/Nuclear Receptor Coactivator 2 (Src-2/Ncoa2) in liver cancer. In contrast, SRC-2 promotes survival and metastasis in prostate cancer cells, suggesting a tissue-specific and context-dependent role for SRC-2 in tumorigenesis...
March 8, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/28270563/the-sleeping-beauty-kissed-awake-new-methods-in-electron-microscopy-to-study-cellular-membranes
#6
REVIEW
Petr Chlanda, Jacomine Krijnse Locker
Electron microscopy (EM) for biological samples, developed in the 1940-1950s, changed our conception about the architecture of eukaryotic cells. It was followed by a period where EM applied to cell biology had seemingly fallen asleep, even though new methods with important implications for modern EM were developed. Among these was the discovery that samples can be preserved by chemical fixation and most importantly by rapid freezing without the formation of crystalline ice, giving birth to the world of cryo-EM...
March 7, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28262785/a-novel-ideal-radionuclide-imaging-system-for-non-invasively-cell-monitoring-built-on-baculovirus-backbone-by-introducing-sleeping-beauty-transposon
#7
Jing Lv, Yu Pan, Huijun Ju, Jinxin Zhou, Dengfeng Cheng, Hongcheng Shi, Yifan Zhang
Sleeping Beauty (SB) transposon is an attractive tool in stable transgene integration both in vitro and in vivo; and we introduced SB transposon into recombinant sodium-iodide symporter baculovirus system (Bac-NIS system) to facilitate long-term expression of recombinant sodium-iodide symporter. In our study, two hybrid baculovirus systems (Bac-eGFP-SB-NeoR and Bac-NIS-SB-NeoR) were successfully constructed and used to infect U87 glioma cells. After G418 selection screening, the Bac-eGFP-SB-NeoR-U87 cells remained eGFP positive, at the 18(th) and 196(th) day post transfection (96...
March 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28255185/sleeping-beauties-cited-in-patents-is-there-also-a-dormitory-of-inventions
#8
Anthony F J van Raan
A 'Sleeping Beauty in Science' is a publication that goes unnoticed ('sleeps') for a long time and then, almost suddenly, attracts a lot of attention ('is awakened by a prince'). In our foregoing study we found that roughly half of the Sleeping Beauties are application-oriented and thus are potential Sleeping Innovations. In this paper we investigate a new topic: Sleeping Beauties that are cited in patents. In this way we explore the existence of a dormitory of inventions. To our knowledge this is the first study of this kind...
2017: Scientometrics
https://www.readbyqxmd.com/read/28254814/long-term-prevention-of-congenital-thrombotic-thrombocytopenic-purpura-in-adamts13-knockout-mice-by-sleeping-beauty-transposon-mediated-gene-therapy
#9
Sebastien Verhenne, Nele Vandeputte, Inge Pareyn, Zsuzsanna Izsvák, Hanspeter Rottensteiner, Hans Deckmyn, Simon F De Meyer, Karen Vanhoorelbeke
OBJECTIVE: Severe deficiency in the von Willebrand factor-cleaving protease ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13) because of mutations in the ADAMTS13 gene can lead to acute episodes of congenital thrombotic thrombocytopenic purpura (TTP), requiring prompt treatment. Current treatment consists of therapeutic or prophylactic infusions of fresh frozen plasma. However, lifelong treatment with plasma products is a stressful therapy for TTP patients...
March 2, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28252665/chromatin-states-shape-insertion-profiles-of-the-piggybac-tol2-and-sleeping-beauty-transposons-and-murine-leukemia-virus
#10
Junko Yoshida, Keiko Akagi, Ryo Misawa, Chikara Kokubu, Junji Takeda, Kyoji Horie
DNA transposons and retroviruses are versatile tools in functional genomics and gene therapy. To facilitate their application, we conducted a genome-wide insertion site profiling of the piggyBac (PB), Tol2 and Sleeping Beauty (SB) transposons and the murine leukemia virus (MLV) in mouse embryonic stem cells (ESCs). PB and MLV preferred highly expressed genes, whereas Tol2 and SB preferred weakly expressed genes. However, correlations with DNase I hypersensitive sites were different for all vectors, indicating that chromatin accessibility is not the sole determinant...
March 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28251929/transposon-insertional-mutagenesis-in-mice-identifies-human-breast-cancer-susceptibility-genes-and-signatures-for-stratification
#11
Liming Chen, Piroon Jenjaroenpun, Andrea Mun Ching Pillai, Anna V Ivshina, Ghim Siong Ow, Motakis Efthimios, Tang Zhiqun, Tuan Zea Tan, Song-Choon Lee, Keith Rogers, Jerrold M Ward, Seiichi Mori, David J Adams, Nancy A Jenkins, Neal G Copeland, Kenneth Hon-Kim Ban, Vladimir A Kuznetsov, Jean Paul Thiery
Robust prognostic gene signatures and therapeutic targets are difficult to derive from expression profiling because of the significant heterogeneity within breast cancer (BC) subtypes. Here, we performed forward genetic screening in mice using Sleeping Beauty transposon mutagenesis to identify candidate BC driver genes in an unbiased manner, using a stabilized N-terminal truncated β-catenin gene as a sensitizer. We identified 134 mouse susceptibility genes from 129 common insertion sites within 34 mammary tumors...
March 1, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28135585/genome-wide-profiling-reveals-remarkable-parallels-between-insertion-site-selection-properties-of-the-mlv-retrovirus-and-the-piggybac-transposon-in-primary-human-cd4-t-cells
#12
Andreas Gogol-Döring, Ismahen Ammar, Saumyashree Gupta, Mario Bunse, Csaba Miskey, Wei Chen, Wolfgang Uckert, Thomas F Schulz, Zsuzsanna Izsvák, Zoltán Ivics
The inherent risks associated with vector insertion in gene therapy need to be carefully assessed. We analyzed the genome-wide distributions of Sleeping Beauty (SB) and piggyBac (PB) transposon insertions as well as MLV retrovirus and HIV lentivirus insertions in human CD4(+) T cells with respect to a panel of 40 chromatin states. The distribution of SB transposon insertions displayed the least deviation from random, while the PB transposon and the MLV retrovirus showed unexpected parallels across all chromatin states...
March 2016: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28122714/sleeping-beauty-awakening-urothelium-from-its-slumber
#13
Zarine R Balsara, Xue Li
The bladder urothelium is essentially quiescent but regenerates readily upon injury. The process of urothelial regeneration harkens back to the process of urothelial development whereby urothelial stem/progenitor cells must proliferate and terminally differentiate to establish all three urothelial layers. How the urothelium regulates the level of proliferation and the timing of differentiation to ensure the precise degree of regeneration is of significant interest in the field. Without a carefully-orchestrated process, urothelial regeneration may be inadequate, thereby exposing the host to toxins or pathogens, or excessive, thereby setting the stage for tumor development...
January 25, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28115300/research-progress-of-tc1-mariner-superfamily
#14
Shen Dan, Chen Cai, Wang Saisai, Chen Wei, Gao Bo, Song Chengyi
With the rapid improvement of sequencing techniques, more and more genome annotations reveal the transposons are the important components of most genomes and present on almost all organisms. Among them, the Tc1/Mariner superfamily represents the most widespread DNA transposons. Until now, fourteen active Tc1/Mariner transposons (Minos, Mos1, etc.) have been identified and some highly active artificial transposons have been created through molecular reconstruction, such as Sleeping Beauty (SB). The transposons such as SB and Mos1 have been widely used as gene transfer vectors in the fields of transgenosis, gene trapping and gene therapy...
January 20, 2017: Yi Chuan, Hereditas
https://www.readbyqxmd.com/read/28081459/targeted-delivery-of-in-situ-pcr-amplified-sleeping-beauty-transposon-genes-to-cancer-cells-with-lipid-based-nanoparticle-like-protocells
#15
Kun Ma, Duo Fu, Dongli Yu, Changhao Cui, Li Wang, Zhaoming Guo, Chuanbin Mao
A Sleeping Beauty (SB) transposon system is made of a transposon plasmid (containing gene encoding a desired functional or therapeutic protein) and a transposase plasmid (encoding an enzyme capable of cutting and pasting the gene into the host cell genome). It is a kind of natural, nonviral gene delivery vehicle, which can achieve efficient genomic insertion, providing long-term transgenic expression. However, before the SB transposon system could play a role in promoting gene expression, it has to be delivered efficiently first across cell membrane and then into cell nuclei...
March 2017: Biomaterials
https://www.readbyqxmd.com/read/28079877/genome-wide-transposon-screening-and-quantitative-insertion-site-sequencing-for-cancer-gene-discovery-in-mice
#16
Mathias J Friedrich, Lena Rad, Iraad F Bronner, Alexander Strong, Wei Wang, Julia Weber, Matthew Mayho, Hannes Ponstingl, Thomas Engleitner, Carolyn Grove, Anja Pfaus, Dieter Saur, Juan Cadiñanos, Michael A Quail, George S Vassiliou, Pentao Liu, Allan Bradley, Roland Rad
Transposon-mediated forward genetics screening in mice has emerged as a powerful tool for cancer gene discovery. It pinpoints cancer drivers that are difficult to find with other approaches, thus complementing the sequencing-based census of human cancer genes. We describe here a large series of mouse lines for insertional mutagenesis that are compatible with two transposon systems, PiggyBac and Sleeping Beauty, and give guidance on the use of different engineered transposon variants for constitutive or tissue-specific cancer gene discovery screening...
February 2017: Nature Protocols
https://www.readbyqxmd.com/read/28035654/seven-days-post-injury-fate-and-effects-of-genetically-labelled-adipose-derived-mesenchymal-cells-on-a-rat-traumatic-brain-injury-experimental-model
#17
Ioanna Dori, Spyros Petrakis, Aggeliki Giannakopoulou, Chryssa Bekiari, Ioannis Grivas, Evangelia K Siska, Georgios Koliakos, Georgios C Papadopoulos
Mesenchymal stromal cells (MSC) have been suggested to have beneficial effects on animal models of traumatic brain injury (TBI), owing to their neurotrophic and immunomodulatory properties. Adipose tissue-derived stromal cells (ASCs) are multipotent MSC that can be harvested with minimally invasive methods, show a high proliferative capacity, low immunogenicity if allogeneic, and can be used in autologous or heterologous settings. In the present study ASCs were genetically labelled using the Sleeping Beauty transposon to express the fluorescent protein Venus...
December 30, 2016: Histology and Histopathology
https://www.readbyqxmd.com/read/28027893/correction-of-recessive-dystrophic-epidermolysis-bullosa-by-transposon-mediated-integration-of-col7a1-in-transplantable-patient-derived-primary-keratinocytes
#18
Maria Carmela Latella, Fabienne Cocchiarella, Laura De Rosa, Giandomenico Turchiano, Manuel A F V Gonçalves, Fernando Larcher, Michele De Luca, Alessandra Recchia
Recessive dystrophic epidermolysis bullosa (RDEB) is caused by defects in type-VII collagen (C7), a protein encoded by the COL7A1 gene and essential for anchoring fibril formation at the dermal-epidermal junction. Gene therapy of RDEB is based on transplantation of autologous epidermal grafts generated from gene-corrected keratinocytes sustaining C7 deposition at the dermal-epidermal junction. Transfer of the COL7A1 gene is complicated by its very large size and repetitive sequence. We report a gene delivery approach based on the Sleeping beauty transposon, which allows integration of a full-length COL7A1 cDNA and secretion of C7 at physiological levels in RDEB keratinocytes without rearrangements or detrimental effects on their clonogenic potential...
December 24, 2016: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/27981621/targeting-%C3%AE-catenin-in-hepatocellular-cancers-induced-by-co-expression-of-mutant-%C3%AE-catenin-and-k-ras-in-mice
#19
Junyan Tao, Rong Zhang, Sucha Singh, Minakshi Poddar, Emily Xu, Michael Oertel, Xin Chen, Shanthi Ganesh, Marc Abrams, Satdarshan P Monga
Recently we have shown that co-expression of hMet and mutant-β-catenin using sleeping beauty transposon/transposase leads to HCC in mice that represents around 10% of human HCC. In the current study, we investigate if Ras activation, which can occur downstream of Met signaling, is sufficient to cause HCC in association with mutant-β-catenin. We also tested therapeutic efficacy of targeting β-catenin in HCC model. We show that mutant-K-Ras (G12D), which leads to Ras activation, cooperates with β-catenin mutants (S33Y, S45Y) to yield HCC in mice...
December 16, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/27966608/slit-robo-gtpase-activating-protein-2-as-a-metastasis-suppressor-in-osteosarcoma
#20
Tracy A Marko, Ghaidan A Shamsan, Elizabeth N Edwards, Paige E Hazelton, Susan K Rathe, Ingrid Cornax, Paula R Overn, Jyotika Varshney, Brandon J Diessner, Branden S Moriarity, M Gerard O'Sullivan, David J Odde, David A Largaespada
Osteosarcoma is the most common primary bone tumor, with metastatic disease responsible for most treatment failure and patient death. A forward genetic screen utilizing Sleeping Beauty mutagenesis in mice previously identified potential genetic drivers of osteosarcoma metastasis, including Slit-Robo GTPase-Activating Protein 2 (Srgap2). This study evaluates the potential role of SRGAP2 in metastases-associated properties of osteosarcoma cell lines through Srgap2 knockout via the CRISPR/Cas9 nuclease system and conditional overexpression in the murine osteosarcoma cell lines K12 and K7M2...
December 14, 2016: Scientific Reports
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