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https://www.readbyqxmd.com/read/29037366/oral-tolerance-induction-in-allergy-kissing-awake-a-sleeping-beauty
#1
EDITORIAL
Rudolf Valenta
No abstract text is available yet for this article.
April 2017: Seminars in Immunology
https://www.readbyqxmd.com/read/28993411/sleeping-beauty-insertional-mutagenesis-in-mice-identifies-drivers-of-steatosis-associated-hepatic-tumor
#2
Barbara R Tschida, Nuri A Temiz, Timothy P Kuka, Lindsey A Lee, Jesse D Riordan, Carlos A Tierrablanca, Robert Hullsiek, Sandra Wagner, Wendy A Hudson, Michael A Linden, Khalid Amin, Pauline J Beckmann, Rachel A Heuer, Aaron L Sarver, Ju Dong Yang, Lewis R Roberts, Joseph H Nadeau, Adam J Dupuy, Vincent W Keng, David Largaespada
Hepatic steatosis is a strong risk factor for the development of hepatocellular carcinoma (HCC), yet little is known about the molecular pathology associated with this factor. In this study, we performed a forward genetic screen using Sleeping Beauty (SB) transposon insertional mutagenesis in mice treated to induce hepatic steatosis, and compared the results to human HCC data. In humans, we determined that steatosis increased the proportion of female HCC patients, a pattern also reflected in mice. Our genetic screen identified 203 candidate steatosis-associated HCC genes, many of which are altered in human HCC and are members of established HCC-driving signaling pathways...
October 9, 2017: Cancer Research
https://www.readbyqxmd.com/read/28964527/gene-therapy-with-the-sleeping-beauty-transposon-system
#3
REVIEW
Partow Kebriaei, Zsuzsanna Izsvák, Suneel A Narayanavari, Harjeet Singh, Zoltán Ivics
The widespread clinical implementation of gene therapy requires the ability to stably integrate genetic information through gene transfer vectors in a safe, effective, and economical manner. The latest generation of Sleeping Beauty (SB) transposon vectors fulfills these requirements, and may overcome limitations associated with viral gene transfer vectors and transient nonviral gene delivery approaches that are prevalent in ongoing clinical trials. The SB system enables high-level stable gene transfer and sustained transgene expression in multiple primary human somatic cell types, thereby representing a highly attractive gene transfer strategy for clinical use...
September 27, 2017: Trends in Genetics: TIG
https://www.readbyqxmd.com/read/28961327/chronic-liver-injury-alters-driver-mutation-profiles-in-hepatocellular-carcinoma
#4
Jesse D Riordan, Charlotte R Feddersen, Barbara R Tschida, Pauline Jackson, Vincent W Keng, Michael A Linden, Khalid Amin, Christopher S Stipp, David A Largaespada, Adam J Dupuy
Most hepatocellular carcinomas (HCCs) develop in a chronically injured liver, yet the extent to which this microenvironment promotes neoplastic transformation or influences selective pressures for genetic drivers of HCC remains unclear. We sought to determine the impact of hepatic injury in an established mouse model of HCC induced by Sleeping Beauty transposon mutagenesis. Chemically-induced chronic liver injury dramatically increased tumor penetrance and significantly altered driver mutation profiles, likely reflecting distinct selective pressures...
September 29, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28949988/generation-of-an-immortalized-mesenchymal-stem-cell-line-producing-a-secreted-biosensor-protein-for-glucose-monitoring
#5
Evangelia K Siska, Itamar Weisman, Jacob Romano, Zoltán Ivics, Zsuzsanna Izsvák, Uriel Barkai, Spyros Petrakis, George Koliakos
Diabetes is a chronic disease characterized by high levels of blood glucose. Diabetic patients should normalize these levels in order to avoid short and long term clinical complications. Presently, blood glucose monitoring is dependent on frequent finger pricking and enzyme based systems that analyze the drawn blood. Continuous blood glucose monitors are already on market but suffer from technical problems, inaccuracy and short operation time. A novel approach for continuous glucose monitoring is the development of implantable cell-based biosensors that emit light signals corresponding to glucose concentrations...
2017: PloS One
https://www.readbyqxmd.com/read/28927521/when-the-guardian-sleeps-reactivation-of-the-p53-pathway-in-cancer
#6
REVIEW
Olaf Merkel, Ninon Taylor, Nicole Prutsch, Philipp B Staber, Richard Moriggl, Suzanne D Turner, Lukas Kenner
The p53 tumor suppressor is inactivated in most cancers, thus suggesting that loss of p53 is a prerequisite for tumor growth. Therefore, its reintroduction through different means bears great clinical potential. After a brief introduction to current knowledge of p53 and its regulation by the ubiquitin-ligases MDM2/MDMX and post-translational modifications, we will discuss small molecules that are able to reactivate specific, frequently observed mutant forms of p53 and their applicability for clinical purposes...
July 2017: Mutation Research
https://www.readbyqxmd.com/read/28920716/transposons-moving-forward-from-preclinical-studies-to-clinical-trials
#7
Jaitip Tipanee, Thierry VandenDriessche, Marinee K Chuah
Transposons have emerged as promising vectors for gene therapy that can potentially overcome some of the limitations of commonly used viral vectors. Transposons stably integrate into the target cell genome, enabling persistent expression of therapeutic genes. Transposons have evolved from being used as basic tools in biomedical research to bona fide therapeutics. Currently, the most promising transposons for gene therapy applications are derived from Sleeping Beauty (SB) or piggyBac (PB). Stable transposition requires co-delivery of the transposon DNA with the corresponding transposase gene, mRNA, or protein...
August 22, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28888423/transposons-as-tools-for-functional-genomics-in-vertebrate-models
#8
REVIEW
Koichi Kawakami, David A Largaespada, Zoltán Ivics
Genetic tools and mutagenesis strategies based on transposable elements are currently under development with a vision to link primary DNA sequence information to gene functions in vertebrate models. By virtue of their inherent capacity to insert into DNA, transposons can be developed into powerful tools for chromosomal manipulations. Transposon-based forward mutagenesis screens have numerous advantages including high throughput, easy identification of mutated alleles, and providing insight into genetic networks and pathways based on phenotypes...
September 6, 2017: Trends in Genetics: TIG
https://www.readbyqxmd.com/read/28870121/wide-awake-and-ready-to-move-20-years-of-non-viral-therapeutic-genome-engineering-with-the-sleeping-beauty-transposon-system
#9
Russ Hodge, Suneel Narayanavari, Zsuzsanna Izsvák, Zoltán Ivics
Gene therapies will only become a widespread tool in the clinical treatment of human diseases with the advent of gene transfer vectors that integrate genetic information stably, safely, effectively, and economically. Two decades after the discovery of the Sleeping Beauty (SB) transposon, it has been transformed into a vector system that is fulfilling these requirements. SB may well overcome some of the limitations associated with viral gene transfer vectors and transient non-viral gene delivery approaches that are being used in the majority of ongoing clinical trials...
September 4, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28858144/exploring-an-unknown-territory-sleeping-beauties-in-the-nursing-research-literature
#10
Peter Kokol, Helena Blažun Vošner, Joeri Vermeulen
BACKGROUND: Sleeping Beauties (SBs) are publications that are scarcely cited in the years immediately following publication but then suddenly become highly cited later. Such publications have unique citation patterns and can reveal important developments in the field in which they appear. OBJECTIVES: No holistic analysis of nursing SBs has been done yet. The aim of this study was to identify and analyze the SB phenomenon in the nursing research literature. METHOD: The corpus for the nursing SB identification was harvested from the Web of Science Core Collection (Thomas Reuters) for the period 1934-2015...
September 2017: Nursing Research
https://www.readbyqxmd.com/read/28855524/rnai-combining-sleeping-beauty-transposon-system-inhibits-ex-vivo-expression-of-foot-and-mouth-disease-virus-vp1-in-transgenic-sheep-cells
#11
Shoulong Deng, Guangdong Li, Kun Yu, Xiuzhi Tian, Feng Wang, Wenting Li, Wuqi Jiang, Pengyun Ji, Hongbing Han, Juncai Fu, Xiaosheng Zhang, Jinlong Zhang, Yixun Liu, Zhengxing Lian, Guoshi Liu
Foot and mouth disease, which is induced by the foot and mouth disease virus (FMDV), takes its toll on the cloven-hoofed domestic animals. The VP1 gene in FMDV genome encodes the viral capsid, a vital element for FMDV replication. Sleeping Beauty (SB) is an active DNA-transposon system responsible for genetic transformation and insertional mutagenesis in vertebrates. In this study, a conserved VP1-shRNA which specifically targets the ovine FMDV-VP1 gene was constructed and combined with SB transposase and transposon...
August 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28854818/recent-advances-in-preclinical-developments-using-adenovirus-hybrid-vectors
#12
Eric Ehrke-Schulz, Wenli Zhang, Jian Gao, Anja Ehrhardt
Adenovirus (Ad) based vectors are efficient gene transfer vehicles to deliver foreign DNA into living organisms offering large cargo capacity low immunogenicity and genotoxicity. As Ad shows low integration rates of their genomes into host chromosomes, vector derived gene expression decreases due to continuous cell cycling in regenerating tissues and dividing cell populations. To overcome this hurdle adenoviral delivery can be combined with mechanisms leading to maintenance of therapeutic DNA and long-term effects of the desired treatment...
August 30, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28852016/the-histidine-rich-peptide-lah4-l1-strongly-promotes-pamam-mediated-transfection-at-low-nitrogen-to-phosphorus-ratios-in-the-presence-of-serum
#13
Nan Liu, Burkhard Bechinger, Regine Süss
Non-viral vectors are widely used and investigated for the delivery of genetic material into cells. However, gene delivery barriers like lysosomal degradation, serum inhibition and transient gene expression so far still limit their clinical applications. Aiming to overcome these limitations, a pH-sensitive hybrid gene vector (PSL complex) was designed by self-assembly of poly(amidoamine) (PAMAM) dendrimers, the histidine-rich peptide LAH4-L1 and the sleeping beauty transposon system (SB transposon system, a plasmid system capable of efficient and precise genomic insertion)...
August 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28838356/sleeping-beauty-developmental-timing-sleep-and-the-circadian-clock-in-caenorhabditis-elegans
#14
M Olmedo, M Merrow, M Geibel
The genetics toolkit is pretty successful in drilling down into minutiae. The big challenge is to integrate the information from this specialty as well as those of biochemistry, physiology, behavior, and anatomy to explain how fundamental biological processes really work. Sleep, the circadian clock and development all qualify as overarching processes that encompass levels from molecule to behavior as part of their known mechanisms. They overlap each other, such that understanding the mechanisms of one can lead to insights into one of the others...
2017: Advances in Genetics
https://www.readbyqxmd.com/read/28807594/thyroid-hormone-receptor-beta-agonist-gc-1-inhibits-met-%C3%AE-catenin-driven-hepatocellular-cancer
#15
Elisabetta Puliga, Qian Min, Junyan Tao, Rong Zhang, Tirthadipa Pradhan-Sundd, Minakshi Poddar, Sucha Singh, Amedeo Columbano, Jinming Yu, Satdarshan P Monga
The thyromimetic agent GC-1 induces hepatocyte proliferation via Wnt/β-catenin signaling and may promoting regeneration in both acute and chronic liver insufficiencies. However, β-catenin activation particularly due to mutations in CTNNB1 is seen in a subset of hepatocellular carcinomas (HCC). Thus, it will be critical to address any effect of GC-1 on HCC growth and development, before its use can be advocated to stimulate regeneration in chronic liver diseases. In the current study, we first examine the effect of GC-1 on β-catenin-TCF4 activity in HCC cell lines harboring wild-type or mutated-CTNNB1...
August 11, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28724549/identification-of-new-tumor-suppressor-genes-in-triple-negative-breast-cancer
#16
Roberto Rangel, Liliana Guzman-Rojas, Takahiro Kodama, Michiko Kodama, Justin Y Newberg, Neal G Copeland, Nancy A Jenkins
Although genomic sequencing has provided a better understating of the genetic landmarks in triple-negative breast cancer (TNBC), functional validation of candidate cancer genes (CCG) remains unsolved. In this study, we used a transposon mutagenesis strategy based on a two-step Sleeping Beauty (SB) forward genetic screen to identify and validate new tumor suppressors (TS) in this disease. We generated 120 siRNAs targeting 40 SB-identified candidate breast cancer TS genes and used them to downregulate expression of these genes in four human TNBC cell lines...
July 19, 2017: Cancer Research
https://www.readbyqxmd.com/read/28719250/sleeping-beauty-awakens-new-interest
#17
Terence R Flotte
No abstract text is available yet for this article.
July 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28716098/awakening-sleeping-beauty-production-of-propionic-acid-in-escherichia-coli-through-the-sbm-operon-requires-the-activity-of-a-methylmalonyl-coa-epimerase
#18
Ricardo Axayacatl Gonzalez-Garcia, Tim McCubbin, Annalena Wille, Manuel Plan, Lars Keld Nielsen, Esteban Marcellin
BACKGROUND: Propionic acid is used primarily as a food preservative with smaller applications as a chemical building block for the production of many products including fabrics, cosmetics, drugs, and plastics. Biological production using propionibacteria would be competitive against chemical production through hydrocarboxylation of ethylene if native producers could be engineered to reach near-theoretical yield and good productivity. Unfortunately, engineering propionibacteria has proven very challenging...
July 17, 2017: Microbial Cell Factories
https://www.readbyqxmd.com/read/28650484/insertional-mutagenesis-identifies-drivers-of-a-novel-oncogenic-pathway-in-invasive-lobular-breast-carcinoma
#19
Sjors M Kas, Julian R de Ruiter, Koen Schipper, Stefano Annunziato, Eva Schut, Sjoerd Klarenbeek, Anne Paulien Drenth, Eline van der Burg, Christiaan Klijn, Jelle J Ten Hoeve, David J Adams, Marco J Koudijs, Jelle Wesseling, Micha Nethe, Lodewyk F A Wessels, Jos Jonkers
Invasive lobular carcinoma (ILC) is the second most common breast cancer subtype and accounts for 8-14% of all cases. Although the majority of human ILCs are characterized by the functional loss of E-cadherin (encoded by CDH1), inactivation of Cdh1 does not predispose mice to develop mammary tumors, implying that mutations in additional genes are required for ILC formation in mice. To identify these genes, we performed an insertional mutagenesis screen using the Sleeping Beauty transposon system in mice with mammary-specific inactivation of Cdh1...
August 2017: Nature Genetics
https://www.readbyqxmd.com/read/28637687/inhibition-of-cdk4-6-by-palbociclib-significantly-extends-survival-in-medulloblastoma-patient-derived-xenograft-mouse-models
#20
Michelle L Cook Sangar, Laura A Genovesi, Madison W Nakamoto, Melissa J Davis, Sue E Knobluagh, Pengxiang Ji, Amanda Millar, Brandon J Wainwright, James M Olson
Purpose: Bioinformatics analysis followed by in vivo studies in patient-derived xenograft (PDX) models were used to identify and validate CDK 4/6 inhibition as an effective therapeutic strategy for medulloblastoma, particularly group 3 MYC-amplified tumors that have the worst clinical prognosis.Experimental Design: A protein interaction network derived from a Sleeping Beauty mutagenesis model of medulloblastoma was used to identify potential novel therapeutic targets. The top hit from this analysis was validated in vivo using PDX models of medulloblastoma implanted subcutaneously in the flank and orthotopically in the cerebellum of mice...
June 21, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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