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https://www.readbyqxmd.com/read/29034641/-establishment-of-l-periaxin-gene-knock-out-rsc96-cell-line
#1
Min Liang, Tingting Peng, Yawei Shi
Periaxin, a protein of noncompact myelin, is specifically expressed in the peripheral nervous system (PNS). There are two protein isoform L-periaxin and S-Periaxin by alternative splicing of periaxin gene, playing an important role in the initiation of myelin formation. So far, 18 different mutation sites in L-periaxin gene have been found to induce the peripheral demyelinating neurological charcot-marie-tooth diseases subtype 4F (CMT4F). The technique of activation of transcription activator-like effector nucleases (TALENS) was used to knock out the L-periaxin gene in RSC 96 cell line of Rattus...
December 25, 2016: Sheng Wu Gong Cheng Xue Bao, Chinese Journal of Biotechnology
https://www.readbyqxmd.com/read/29021890/zebrafish-knockout-of-down-syndrome-gene-dyrk1a-shows-social-impairments-relevant-to-autism
#2
Oc-Hee Kim, Hyun-Ju Cho, Enna Han, Ted Inpyo Hong, Krishan Ariyasiri, Jung-Hwa Choi, Kyu-Seok Hwang, Yun-Mi Jeong, Se-Yeol Yang, Kweon Yu, Doo-Sang Park, Hyun-Woo Oh, Erica E Davis, Charles E Schwartz, Jeong-Soo Lee, Hyung-Goo Kim, Cheol-Hee Kim
BACKGROUND: DYRK1A maps to the Down syndrome critical region at 21q22. Mutations in this kinase-encoding gene have been reported to cause microcephaly associated with either intellectual disability or autism in humans. Intellectual disability accompanied by microcephaly was recapitulated in a murine model by overexpressing Dyrk1a which mimicked Down syndrome phenotypes. However, given embryonic lethality in homozygous knockout (KO) mice, no murine model studies could present sufficient evidence to link Dyrk1a dysfunction with autism...
2017: Molecular Autism
https://www.readbyqxmd.com/read/29019352/hot-news-gene-therapy-with-crispr-cas9-coming-to-age-for-hiv-cure
#3
Vicente Soriano
The huge success of current antiretroviral therapy is mediated by a triple effect: (i) Halting progression to AIDS in infected persons; (ii) reducing the risk of transmission to contacts (treatment as prevention); and (iii) minimizing the risk of HIV acquisition treating uninfected persons at risk (pre-exposure prophylaxis). However, UNAIDS has estimated that only 70% of infected people globally are diagnosed, only 53% are treated, and overall 44% have undetectable viral load, which is the necessary request for ensuring any antiretroviral benefit...
October 11, 2017: AIDS Reviews
https://www.readbyqxmd.com/read/28981088/hsf4-regulates-lens-fiber-cell-differentiation-by-activating-p53-and-its-downstream-regulators
#4
Meng Gao, Yuwen Huang, Ling Wang, Mi Huang, Fei Liu, Shengjie Liao, Shanshan Yu, Zhaojing Lu, Shanshan Han, Xuebin Hu, Zhen Qu, Xiliang Liu, Tinsae Assefa Yimer, Lifang Yang, Zhaohui Tang, David Wan-Cheng Li, Mugen Liu
Cataract refers to opacities of the lens that impede the passage of light. Mutations in heat shock transcription factor 4 (HSF4) have been associated with cataract; however, the mechanisms regarding how mutations in HSF4 cause cataract are still obscure. In this study, we generated an hsf4 knockout zebrafish model using TALEN technology. The mutant zebrafish developed an early-onset cataract with multiple developmental defects in lens. The epithelial cells of the lens were overproliferated, resulting in the overabundance of lens fiber cells in hsf4(null) zebrafish lens...
October 5, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28965220/molecular-tools-for-gene-manipulation-in-filamentous-fungi
#5
REVIEW
Shunxian Wang, Haiqin Chen, Xin Tang, Hao Zhang, Wei Chen, Yong Q Chen
Functional genomics of filamentous fungi has gradually uncovered gene information for constructing 'cell factories' and controlling pathogens. Available gene manipulation methods of filamentous fungi include random integration methods, gene targeting technology, gene editing with artificial nucleases and RNA technology. This review describes random gene integration constructed by restriction enzyme-mediated integration (REMI); Agrobacterium-mediated transformation (AMT); transposon-arrayed gene knockout (TAGKO); gene targeting technology, mainly about homologous recombination; and modern gene editing strategies containing transcription activator-like effector nucleases (TALENs) and a clustered regularly interspaced short palindromic repeat/associated protein system (CRISPR/Cas) developed in filamentous fungi and RNA technology including RNA interference (RNAi) and ribozymes...
September 30, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28964684/comparison-of-the-influence-of-corneo-scleral-and-scleral-lenses-on-ocular-surface-and-tear-film-metrics-in-a-presbyopic-population
#6
Edouard Lafosse, Daniel Monsálvez Romín, José-Juan Esteve-Taboada, James S Wolffsohn, Cristian Talens-Estarelles, Santiago García-Lázaro
PURPOSE: To assess and compare the effect of the corneo-scleral lenses (C-ScL) and scleral lenses (ScL) on tear film parameters and central corneal thickness (CCT) in healthy presbyopic subjects. METHODS: Thirty subjects wore two contact lenses (CLs), randomly assigned, of neutral power, but of different diameters, 12.7mm (C-ScL) and 18mm (ScL) and being equal in the others parameters: material (HS100) and centre thickness (0.29mm). At baseline, 20min after insertion and at 8h, the tear meniscus area (TMA) and CCT was measured (with optical coherence tomography) as well as tear osmolarity...
September 27, 2017: Contact Lens & Anterior Eye: the Journal of the British Contact Lens Association
https://www.readbyqxmd.com/read/28962583/engineering-human-ventricular-heart-muscles-based-on-a-highly-efficient-system-for-purification-of-human-pluripotent-stem-cell-derived-ventricular-cardiomyocytes
#7
Bin Li, Hui Yang, Xiaochen Wang, Yongkun Zhan, Wei Sheng, Huanhuan Cai, Haoyang Xin, Qianqian Liang, Ping Zhou, Chao Lu, Ruizhe Qian, Sifeng Chen, Pengyuan Yang, Jianyi Zhang, Weinian Shou, Guoying Huang, Ping Liang, Ning Sun
BACKGROUND: Most infarctions occur in the left anterior descending coronary artery and cause myocardium damage of the left ventricle. Although current pluripotent stem cells (PSCs) and directed cardiac differentiation techniques are able to generate fetal-like human cardiomyocytes, isolation of pure ventricular cardiomyocytes has been challenging. For repairing ventricular damage, we aimed to establish a highly efficient purification system to obtain homogeneous ventricular cardiomyocytes and prepare engineered human ventricular heart muscles in a dish...
September 29, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28960187/genome-engineering-a-new-approach-to-gene-therapy-for-neuromuscular-disorders
#8
REVIEW
Christopher E Nelson, Jacqueline N Robinson-Hamm, Charles A Gersbach
For many neuromuscular disorders, including Duchenne muscular dystrophy, spinal muscular atrophy and myotonic dystrophy, the genetic causes are well known. Gene therapy holds promise for the treatment of these monogenic neuromuscular diseases, and many such therapies have made substantial strides toward clinical translation. Recently, genome engineering tools, including targeted gene editing and gene regulation, have become available to correct the underlying genetic mutations that cause these diseases. In particular, meganucleases, zinc finger nucleases, TALENs, and the CRISPR-Cas9 system have been harnessed to make targeted and specific modifications to the genome...
September 29, 2017: Nature Reviews. Neurology
https://www.readbyqxmd.com/read/28934905/talen-mediated-targeted-editing-of-the-gde5-gene-suppresses-fibroblastic-cell-proliferation
#9
Minako Nakamura, Thanutchaporn Kumrungsee, Tetsushi Sakuma, Takashi Yamamoto, Noriyuki Yanaka
In this study, we investigated the physiological function of glycerophosphodiesterase 5 (GDE5) in the proliferation of NIH3T3 fibroblasts. We used transcription activator-like effector nuclease (TALEN) in NIH3T3 cells with an intron targeting-mediated GDE5 gene knockout. The heterozygously GDE5-targeted NIH3T3 fibroblasts were isolated and showed decreased cell proliferation and up-regulation of EGFR mRNA expression, indicating that GDE5 modulates fibroblastic cell proliferation.
September 22, 2017: Bioscience, Biotechnology, and Biochemistry
https://www.readbyqxmd.com/read/28926587/functional-characterization-of-zebrafish-orthologs-of-the-human-beta-3-glucosyltransferase-b3glct-gene-mutated-in-peters-plus-syndrome
#10
Eric Weh, Hideyuki Takeuchi, Sanaa Muheisen, Robert S Haltiwanger, Elena V Semina
Peters Plus Syndrome (PPS) is a rare autosomal recessive disease characterized by ocular defects, short stature, brachydactyly, characteristic facial features, developmental delay and other highly variable systemic defects. Classic PPS is caused by loss-of-function mutations in the B3GLCT gene encoding for a β3-glucosyltransferase that catalyzes the attachment of glucose via a β1-3 glycosidic linkage to O-linked fucose on thrombospondin type 1 repeats (TSRs). B3GLCT was shown to participate in a non-canonical ER quality control mechanism; however, the exact molecular processes affected in PPS are not well understood...
2017: PloS One
https://www.readbyqxmd.com/read/28925369/generation-of-a-gene-corrected-isogenic-control-ipsc-line-from-cystic-fibrosis-patient-specific-ipscs-homozygous-for-p-phe508del-mutation-mediated-by-talens-and-ssodn
#11
Sylvia Merkert, Christien Bednarski, Gudrun Göhring, Toni Cathomen, Ulrich Martin
Cystic fibrosis (CF) is a monogenetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which affects multiple organs. Human induced pluripotent stem cells (iPSCs) derived from CF patients and the generation of isogeneic gene-corrected control cell lines enable disease modelling, drug discovery or toxicological studies and therefore the development of CF patient-specific therapies. We have previously generated a hiPSC line from a CF patient homozygous for the p...
August 2017: Stem Cell Research
https://www.readbyqxmd.com/read/28919449/genome-editing-in-fishes-and-their-applications
#12
Bo Zhu, Wei Ge
There have been revolutionary progresses in genome engineering in the past few years. The newly-emerged genome editing technologies including zinc-finger nuclease (ZFN), transcription activator-like effector nuclease (TALEN) and clustered regularly interspaced short palindromic repeats associated with Cas9 (CRISPR/Cas9) have enabled biological scientists to perform efficient and precise targeted genome editing in different species. Fish represent the largest group of vertebrates with many species having values for both scientific research and aquaculture industry...
September 14, 2017: General and Comparative Endocrinology
https://www.readbyqxmd.com/read/28913801/targeted-mutagenesis-in-hexaploid-bread-wheat-using-the-talen-and-crispr-cas-systems
#13
Yanpeng Wang, Yuan Zong, Caixia Gao
The use of sequence-specific transcription activator-like effector nucleases (TALENs) and the clustered regularly interspaced short palindromic repeats-associated system (CRISPR/Cas9) have provided powerful reverse genetic approaches to the targeted modification of genomes in numerous organisms. Both systems have been employed to generate loss-of-function alleles in bread wheat, by targeting multiple and single copies of genes. Here we present protocols for modifying the wheat genome using the two systems. The protocols include the design of TALEN and CRISPR/Cas9 target sites and their construction, evaluation of their activities in protoplasts, transformation of plants, and mutation screening...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28913702/impaired-fertility-and-motor-function-in-a-zebrafish-model-for-classic-galactosemia
#14
Jo M Vanoevelen, M Estela Rubio-Gozalbo, Britt van Erven, Jörgen Bierau, Xiaoping Huang, Gerard T Berry, Rein Vos, Ana I Coelho
Classic galactosemia is a genetic disorder of galactose metabolism, caused by severe deficiency of galactose-1-phosphate uridylyltransferase (GALT) enzyme activity due to mutations of the GALT gene. Its pathogenesis is still not fully elucidated, and a therapy that prevents chronic impairments is lacking. In order to move research forward, there is a high need for a novel animal model, which allows organ studies throughout development and high-throughput screening of pharmacologic compounds. Here, we describe the generation of a galt knockout zebrafish model and present its phenotypical characterization...
September 14, 2017: Journal of Inherited Metabolic Disease
https://www.readbyqxmd.com/read/28911205/a-zebrafish-model-of-x-linked-adrenoleukodystrophy-recapitulates-key-disease-features-and-demonstrates-a-developmental-requirement-for-abcd1-in-oligodendrocyte-patterning-and-myelination
#15
Lauren R Strachan, Tamara J Stevenson, Briana Freshner, Matthew D Keefe, D Miranda Bowles, Joshua L Bonkowsky
X-linked adrenoleukodystrophy (ALD) is a devastating inherited neurodegenerative disease caused by defects in the ABCD1 gene and affecting peripheral and central nervous system myelin. ABCD1 encodes a peroxisomal transmembrane protein required for very long chain fatty acid (VLCFA) metabolism. We show that zebrafish (Danio rerio) Abcd1 is highly conserved at the amino acid level with human ABCD1, and during development is expressed in homologous regions including the central nervous system and adrenal glands...
September 15, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28905511/talen-mediated-targeted-mutagenesis-of-more-than-100-comt-copies-alleles-in-highly-polyploid-sugarcane-improves-saccharification-efficiency-without-compromising-biomass-yield
#16
Baskaran Kannan, Je Hyeong Jung, Geoffrey W Moxley, Sun-Mi Lee, Fredy Altpeter
Sugarcane is the world's most efficient feedstock for commercial production of bioethanol due to its superior biomass production and accumulation of sucrose in stems. Integrating first and second generation ethanol conversion processes will enhance the biofuel yield per unit area by utilizing both sucrose as well as cell wall bound sugars for fermentation. RNAi suppression of the lignin biosynthetic gene caffeic acid O-methyltransferase (COMT) has been demonstrated to improve bioethanol production from lignocellulosic biomass...
September 14, 2017: Plant Biotechnology Journal
https://www.readbyqxmd.com/read/28904745/genome-editing-of-the-hiv-co-receptors-ccr5-and-cxcr4-by-crispr-cas9-protects-cd4-t-cells-from-hiv-1-infection
#17
Zhepeng Liu, Shuliang Chen, Xu Jin, Qiankun Wang, Kongxiang Yang, Chenlin Li, Qiaoqiao Xiao, Panpan Hou, Shuai Liu, Shaoshuai Wu, Wei Hou, Yong Xiong, Chunyan Kong, Xixian Zhao, Li Wu, Chunmei Li, Guihong Sun, Deyin Guo
BACKGROUND: The main approach to treat HIV-1 infection is combination antiretroviral therapy (cART). Although cART is effective in reducing HIV-1 viral load and controlling disease progression, it has many side effects, and is expensive for HIV-1 infected patients who must remain on lifetime treatment. HIV-1 gene therapy has drawn much attention as studies of genome editing tools have progressed. For example, zinc finger nucleases (ZFN), transcription activator like effector nucleases (TALEN) and clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 have been utilized to successfully disrupt the HIV-1 co-receptors CCR5 or CXCR4, thereby restricting HIV-1 infection...
2017: Cell & Bioscience
https://www.readbyqxmd.com/read/28903419/development-of-zebrafish-medulloblastoma-like-pnet-model-by-talen-mediated-somatic-gene-inactivation
#18
Jaegal Shim, Jung-Hwa Choi, Moon-Hak Park, Hyena Kim, Jong Hwan Kim, Seon-Young Kim, Dongwan Hong, Sunshin Kim, Ji Eun Lee, Cheol-Hee Kim, Jeong-Soo Lee, Young-Ki Bae
Genetically engineered animal tumor models have traditionally been generated by the gain of single or multiple oncogenes or the loss of tumor suppressor genes; however, the development of live animal models has been difficult given that cancer phenotypes are generally induced by somatic mutation rather than by germline genetic inactivation. In this study, we developed somatically mutated tumor models using TALEN-mediated somatic gene inactivation of cdkn2a/b or rb1 tumor suppressor genes in zebrafish. One-cell stage injection of cdkn2a/b-TALEN mRNA resulted in malignant peripheral nerve sheath tumors with high frequency (about 39%) and early onset (about 35 weeks of age) in F0 tp53(e7/e7) mutant zebrafish...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28903395/tgf-%C3%AE-2-induced-angptl4-expression-promotes-tumor-progression-and-osteoclast-differentiation-in-giant-cell-tumor-of-bone
#19
Bo Li, Ming Qian, Hao Cao, Qi Jia, Zhipeng Wu, Xinghai Yang, Tianyi Ma, Haifeng Wei, Tianrui Chen, Jianru Xiao
Although emerging studies have implicated that Aiopoietin-like 4 Protein (ANGPTL4) is related to the aggressiveness and metastasis of many tumors, the role of ANGPLT4 in giant cell tumor (GCT) of bone was rarely investigated. The mechanism of ANGPLT4 in tumor-induced osteoclastogenesis still remains unclear. In this study, we first demonstrated that ANGPTL4 was highly expressed in GCT compared to normal tissues, while we showed that TGF-β2 released by osteoclasts induced bone resorption could increase the expression of ANGPTL4 in GCTSCs...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28899668/the-sp7-gene-is-required-for-maturation-of-osteoblast-lineage-cells-in-medaka-oryzias-latipes-vertebral-column-development
#20
Yuki Azetsu, Keiji Inohaya, Yoshiro Takano, Masato Kinoshita, Mai Tasaki, Akira Kudo
Sp7 is a zinc finger transcription factor that is essential for osteoblast differentiation in mammals. To verify the characteristic features of osteoblast-lineage cells in teleosts, we established medaka sp7 mutants using a transcription activator-like effector nuclease (TALEN) genome editing system. These mutants showed severe defects in the formation of skeletal structures. In particular, the neural and the hemal arches were not formed, although the chordal centra were formed. Analysis of the transgenic medaka revealed that sp7 mutant had normal distribution of type X collagen a1 a (col10a1a)-positive osteoblast-like cells around the centrum and at the proximal region of the vertebral arch...
September 9, 2017: Developmental Biology
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