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https://www.readbyqxmd.com/read/29218067/perceived-age-and-life-style-the-specific-contributions-of-seven-factors-involved-in-health-and-beauty
#1
Victor Gabriel Clatici, Daniel Racoceanu, Claude Dalle, Cristiana Voicu, Lucia Tomas-Aragones, Servando E Marron, Uwe Wollina, Simona Fica
OBJECTIVES: The skin is a dynamic, visible organ, showing the most obvious signs of aging. The mechanisms of extrinsic aging, most of them presented in this paper, are currently well known and also the only ones that can be counteracted. Therefore, the transition of this knowledge in the general population is of the most importance, in order to introduce healthy aging strategies, to prevent the development of chronic or malignant diseases and psychological burden related to old age. MATERIALS AND METHODS: A thorough review of the literature has been performed in order to identify the main factors involved in skin health and aging...
September 2017: Mædica
https://www.readbyqxmd.com/read/29130932/p120-catenin-is-an-obligate-haploinsufficient-tumor-suppressor-in-intestinal-neoplasia
#2
Sarah P Short, Jumpei Kondo, Whitney G Smalley-Freed, Haruna Takeda, Michael R Dohn, Anne E Powell, Robert H Carnahan, Mary K Washington, Manish Tripathi, D Michael Payne, Nancy A Jenkins, Neal G Copeland, Robert J Coffey, Albert B Reynolds
p120-Catenin (p120) functions as a tumor suppressor in intestinal cancer, but the mechanism is unclear. Here, using conditional p120 knockout in Apc-sensitized mouse models of intestinal cancer, we have identified p120 as an "obligatory" haploinsufficient tumor suppressor. Whereas monoallelic loss of p120 was associated with a significant increase in tumor multiplicity, loss of both alleles was never observed in tumors from these mice. Moreover, forced ablation of the second allele did not further enhance tumorigenesis, but instead induced synthetic lethality in combination with Apc loss of heterozygosity...
November 13, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29089466/preclinical-and-clinical-advances-in-transposon-based-gene-therapy
#3
Jaitip Tipanee, Yoke Chin Chai, Thierry VandenDriessche, Marinee K Chuah
Transposons derived from Sleeping Beauty (SB), piggyBac (PB) or Tol2 typically require cotransfection of transposon DNA with a transposase either as an expression plasmid or mRNA. Consequently, this results in genomic integration of the potentially therapeutic gene into chromosomes of the desired target cells and thus conferring stable expression. Nonviral transfection methods are typically preferred to deliver the transposon components in to the target cells. However, these methods do not match the efficacy typically attained with viral vectors and are sometimes associated with cellular toxicity evoked by the DNA itself...
October 31, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/29077768/secretion-of-a-recombinant-protein-without-a-signal-peptide-by-the-exocrine-glands-of-transgenic-rabbits
#4
Andrea Kerekes, Orsolya Ivett Hoffmann, Gergely Iski, Nándor Lipták, Elen Gócza, Wilfried A Kues, Zsuzsanna Bősze, László Hiripi
Transgenic rabbits carrying mammary gland specific gene constructs are extensively used for excreting recombinant proteins into the milk. Here, we report refined phenotyping of previously generated Venus transposon-carrying transgenic rabbits with particular emphasis on the secretion of the reporter protein by exocrine glands, such as mammary, salivary, tear and seminal glands. The Sleeping Beauty (SB) transposon transgenic construct contains the Venus fluorophore cDNA, but without a signal peptide for the secretory pathway, driven by the ubiquitous CAGGS (CAG) promoter...
2017: PloS One
https://www.readbyqxmd.com/read/29059366/sbcddb-sleeping-beauty-cancer-driver-database-for-gene-discovery-in-mouse-models-of-human-cancers
#5
Justin Y Newberg, Karen M Mann, Michael B Mann, Nancy A Jenkins, Neal G Copeland
Large-scale oncogenomic studies have identified few frequently mutated cancer drivers and hundreds of infrequently mutated drivers. Defining the biological context for rare driving events is fundamentally important to increasing our understanding of the druggable pathways in cancer. Sleeping Beauty (SB) insertional mutagenesis is a powerful gene discovery tool used to model human cancers in mice. Our lab and others have published a number of studies that identify cancer drivers from these models using various statistical and computational approaches...
October 20, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29037366/oral-tolerance-induction-in-allergy-kissing-awake-a-sleeping-beauty
#6
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
#7
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
#8
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...
November 2017: Trends in Genetics: TIG
https://www.readbyqxmd.com/read/28961327/chronic-liver-injury-alters-driver-mutation-profiles-in-hepatocellular-carcinoma
#9
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
#10
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
#11
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
#12
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...
November 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28888423/transposons-as-tools-for-functional-genomics-in-vertebrate-models
#13
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...
November 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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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-%C3%AE-agonist-gc-1-inhibits-met-%C3%AE-catenin-driven-hepatocellular-cancer
#20
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 promote regeneration in both acute and chronic liver insufficiencies. However, β-catenin activation due to mutations in CTNNB1 is seen in a subset of hepatocellular carcinomas (HCC). Thus, it is 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 this study, we first examined the effect of GC-1 on β-catenin-T cell factor 4 activity in HCC cell lines harboring wild-type or mutated-CTNNB1...
November 2017: American Journal of Pathology
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