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https://www.readbyqxmd.com/read/28324650/genome-engineering-of-virulent-lactococcal-phages-using-crispr-cas9
#1
Marie-Laurence Lemay, Denise M Tremblay, Sylvain Moineau
Phages are biological entities found in every ecosystem. Although much has been learned about them in past decades, significant knowledge gaps remain. Manipulating virulent phage genomes is challenging. To date, no efficient gene-editing tools exist for engineering virulent lactococcal phages. Lactococcus lactis is a bacterium extensively used as a starter culture in various milk fermentation processes and its phage sensitivity poses a constant risk to the cheese industry. The lactococcal phage p2 is one of the best-studied models for these virulent phages...
March 21, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28318500/mutations-in-tmem260-cause-a-pediatric-neurodevelopmental-cardiac-and-renal-syndrome
#2
Asaf Ta-Shma, Tahir N Khan, Asaf Vivante, Jason R Willer, Pavle Matak, Chaim Jalas, Ben Pode-Shakked, Yishay Salem, Yair Anikster, Friedhelm Hildebrandt, Nicholas Katsanis, Orly Elpeleg, Erica E Davis
Despite the accelerated discovery of genes associated with syndromic traits, the majority of families affected by such conditions remain undiagnosed. Here, we employed whole-exome sequencing in two unrelated consanguineous kindreds with central nervous system (CNS), cardiac, renal, and digit abnormalities. We identified homozygous truncating mutations in TMEM260, a locus predicted to encode numerous splice isoforms. Systematic expression analyses across tissues and developmental stages validated two such isoforms, which differ in the utilization of an internal exon...
March 11, 2017: American Journal of Human Genetics
https://www.readbyqxmd.com/read/28316978/identification-of-significant-pathways-induced-by-pax5-haploinsufficiency-based-on-protein-protein-interaction-networks-and-cluster-analysis-in-raji-cell-line
#3
Jia Gu, TongJuan Li, Lei Zhao, Xue Liang, Xing Fu, Jue Wang, Zhen Shang, Wei Huang, Jianfeng Zhou
PAX5 encodes a transcription factor essential for B-cell differentiation, and PAX5 haploinsufficiency is involved in tumorigenesis. There were few studies on how PAX5 haploinsufficiency regulated genes expression to promote tumorigenesis. In this study, we constructed the cell model of PAX5 haploinsufficiency using gene editing technology in Raji cells, detected differentially expressed genes in PAX5 haploinsufficiency Raji cells, and used protein-protein interaction networks and cluster analysis to comprehensively investigate the cellular pathways involved in PAX5 haploinsufficiency...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28315486/crispr-cas9-mediated-genome-editing-in-plants
#4
Xuejun Liu, Chuanxiao Xie, Huaijun Si, Jinxiao Yang
The increasing burden of the world's population on agriculture necessitates the development of more robust crops. As the amount of information from sequenced crop genomes increases, technology can be used to investigate the function of genes in detail and to design improved crops at the molecular level. Recently, an RNA-programmed genome-editing system composed of a clustered regularly interspaced short palindromic repeats (CRISPR)-encoded guide RNA and the nuclease Cas9 has provided a powerful platform to achieve these goals...
March 14, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28315297/paxillin-genes-and-actomyosin-contractility-regulate-myotome-morphogenesis-in-zebrafish
#5
Andrew E Jacob, Jeffrey D Amack, Christopher E Turner
Paxillin (Pxn) is a key adapter protein and signaling regulator at sites of cell-extracellular matrix (ECM) adhesion. Here, we investigated the role of Pxn during vertebrate development using the zebrafish embryo as a model system. We have characterized two Pxn genes, pxna and pxnb, in zebrafish that are maternally supplied and expressed in multiple tissues. Gene editing and antisense gene knockdown approaches were used to uncover Pxn functions during zebrafish development. While mutation of either pxna or pxnb alone did not cause gross embryonic phenotypes, double mutants lacking maternally supplied pxna or pxnb displayed defects in cardiovascular, axial, and skeletal muscle development...
March 14, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28304362/bdnf-variants-may-modulate-long-term-visual-memory-performance-in-a-healthy-cohort
#6
Nesli Avgan, Heidi G Sutherland, Lauren K Spriggens, Chieh Yu, Omar Ibrahim, Claire Bellis, Larisa M Haupt, David H K Shum, Lyn R Griffiths
Brain-derived neurotrophic factor (BDNF) is involved in numerous cognitive functions including learning and memory. BDNF plays an important role in synaptic plasticity in humans and rats with BDNF shown to be essential for the formation of long-term memories. We previously identified a significant association between the BDNF Val66Met polymorphism (rs6265) and long-term visual memory (p-value = 0.003) in a small cohort (n = 181) comprised of healthy individuals who had been phenotyped for various aspects of memory function...
March 17, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28303292/editing-the-genome-of-hipsc-with-crispr-cas9-disease-models
#7
REVIEW
Andrew R Bassett
The advent of human-induced pluripotent stem cell (hiPSC) technology has provided a unique opportunity to establish cellular models of disease from individual patients, and to study the effects of the underlying genetic aberrations upon multiple different cell types, many of which would not normally be accessible. Combining this with recent advances in genome editing techniques such as the clustered regularly interspaced short palindromic repeat (CRISPR) system has provided an ability to repair putative causative alleles in patient lines, or introduce disease alleles into a healthy "WT" cell line...
March 16, 2017: Mammalian Genome: Official Journal of the International Mammalian Genome Society
https://www.readbyqxmd.com/read/28303022/to-cleave-or-not-to-cleave-therapeutic-gene-editing-with-and-without-programmable-nucleases
#8
Tod M Woolf, Channabasavaiah B Gurumurthy, Frederick Boyce, Eric B Kmiec
No abstract text is available yet for this article.
March 17, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28302908/tubulin-isotype-substitution-revealed-that-isotype-composition-modulates-microtubule-dynamics-in-c-elegans-embryos
#9
Yu Honda, Kenta Tsuchiya, Eisuke Sumiyoshi, Nami Haruta, Asako Sugimoto
Microtubules (MTs) are polymers composed of α- and β-tubulin heterodimers, which are generally encoded by multiple gene loci. Despite implications of distinct properties of isotypes, how they contribute to diverse MT dynamics in vivo remains unclear. Here, using genome editing and RNAi depletion of tubulin isotypes, we demonstrate that four tubulin isotypes (hereafter α1, α2, β1 and β2) cooperatively confer distinct MT properties in Caenorhabditis elegans early embryos. GFP insertion into each isotype locus reveals their distinct expression levels and MT incorporation rates...
March 16, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28302840/promise-and-challenges-of-gene-editing
#10
EDITORIAL
Julia Fahrenkamp-Uppenbrink
No abstract text is available yet for this article.
March 17, 2017: Science
https://www.readbyqxmd.com/read/28298437/riding-the-metalloproteinase-roller-coaster
#11
Gillian Murphy
To many of us in the field, working on Matrix Metalloproteinases (MMPs) has felt like riding a roller coaster, traveling through times of both excitement and despair. I was fortunate to join the ride when it was a mere carousel of three activities thought to target the proteins that comprise the extracellular matrix (ECM). New technologies brought the thrills of discovery, as we uncovered specific proteinase genes and defined specialised activities in different cellular processes. The MMPs and the sister families of 'A Disintegrin And Metalloproteinase' (ADAMs), ADAMs with ThromboSpondin domains (ADAM-TS) and Astacins are now recognised as key signalling 'scissors' that drive rapid changes in a plethora of cellular pathways...
March 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28298224/transcriptional-reprogramming-in-yeast-using-dcas9-and-combinatorial-grna-strategies
#12
Emil D Jensen, Raphael Ferreira, Tadas Jakočiūnas, Dushica Arsovska, Jie Zhang, Ling Ding, Justin D Smith, Florian David, Jens Nielsen, Michael K Jensen, Jay D Keasling
BACKGROUND: Transcriptional reprogramming is a fundamental process of living cells in order to adapt to environmental and endogenous cues. In order to allow flexible and timely control over gene expression without the interference of native gene expression machinery, a large number of studies have focused on developing synthetic biology tools for orthogonal control of transcription. Most recently, the nuclease-deficient Cas9 (dCas9) has emerged as a flexible tool for controlling activation and repression of target genes, by the simple RNA-guided positioning of dCas9 in the vicinity of the target gene transcription start site...
March 15, 2017: Microbial Cell Factories
https://www.readbyqxmd.com/read/28297579/endothelial-cells-promote-expansion-of-long-term-engrafting-marrow-hematopoietic-stem-and-progenitor-cells-in-primates
#13
Jennifer L Gori, Jason M Butler, Balvir Kunar, Michael G Poulos, Michael Ginsberg, Daniel J Nolan, Zachary K Norgaard, Jennifer E Adair, Shahin Rafii, Hans-Peter Kiem
Successful expansion of bone marrow (BM) hematopoietic stem and progenitor cells (HSPCs) would benefit many HSPC transplantation and gene therapy/editing applications. However, current expansion technologies have been limited by a loss of multipotency and self-renewal properties ex vivo. We hypothesized that an ex vivo vascular niche would provide prohematopoietic signals to expand HSPCs while maintaining multipotency and self-renewal. To test this hypothesis, BM autologous CD34(+) cells were expanded in endothelial cell (EC) coculture and transplanted in nonhuman primates...
March 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28295439/genome-engineering-and-modification-toward-synthetic-biology-for-the-production-of-antibiotics
#14
REVIEW
Xuan Zou, Lianrong Wang, Zhiqiang Li, Jie Luo, Yunfu Wang, Zixin Deng, Shiming Du, Shi Chen
Antibiotic production is often governed by large gene clusters composed of genes related to antibiotic scaffold synthesis, tailoring, regulation, and resistance. With the expansion of genome sequencing, a considerable number of antibiotic gene clusters has been isolated and characterized. The emerging genome engineering techniques make it possible towards more efficient engineering of antibiotics. In addition to genomic editing, multiple synthetic biology approaches have been developed for the exploration and improvement of antibiotic natural products...
March 15, 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/28295376/both-maternally-and-paternally-imprinted-genes-regulate-seed-development-in-rice
#15
Jingya Yuan, Sushu Chen, Wu Jiao, Longfei Wang, Limei Wang, Wenxue Ye, Jie Lu, Delin Hong, Siliang You, Zhukuan Cheng, Dong-Lei Yang, Z Jeffrey Chen
Genetic imprinting refers to the unequal expression of paternal and maternal alleles of a gene in sexually reproducing organisms, including mammals and flowering plants. Although many imprinted genes have been identified in plants, the functions of these imprinted genes have remained largely uninvestigated. We report genome-wide analysis of gene expression, DNA methylation and small RNAs in the rice endosperm and functional tests of five imprinted genes during seed development using Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR-associated gene9 (CRISPR/Cas9) gene editing technology...
March 13, 2017: New Phytologist
https://www.readbyqxmd.com/read/28294295/breast-cancer-major-changes-in-the-american-joint-committee-on-cancer-eighth-edition-cancer-staging-manual
#16
Armando E Giuliano, James L Connolly, Stephen B Edge, Elizabeth A Mittendorf, Hope S Rugo, Lawrence J Solin, Donald L Weaver, David J Winchester, Gabriel N Hortobagyi
Answer questions and earn CME/CNE The revision of the eighth edition of the primary tumor, lymph node, and metastasis (TNM) classification of the American Joint Commission of Cancer (AJCC) for breast cancer was determined by a multidisciplinary team of breast cancer experts. The panel recognized the need to incorporate biologic factors, such as tumor grade, proliferation rate, estrogen and progesterone receptor expression, human epidermal growth factor 2 (HER2) expression, and gene expression prognostic panels into the staging system...
March 14, 2017: CA: a Cancer Journal for Clinicians
https://www.readbyqxmd.com/read/28293040/gene-editing-using-crispr-cas9-for-the-treatment-of-lung-cancer
#17
EDITORIAL
Andres Castillo
No abstract text is available yet for this article.
December 30, 2016: Colombia Médica: CM
https://www.readbyqxmd.com/read/28292896/loss-of-lmod1-impairs-smooth-muscle-cytocontractility-and-causes-megacystis-microcolon-intestinal-hypoperistalsis-syndrome-in-humans-and-mice
#18
Danny Halim, Michael P Wilson, Daniel Oliver, Erwin Brosens, Joke B G M Verheij, Yu Han, Vivek Nanda, Qing Lyu, Michael Doukas, Hans Stoop, Rutger W W Brouwer, Wilfred F J van IJcken, Orazio J Slivano, Alan J Burns, Christine K Christie, Karen L de Mesy Bentley, Alice S Brooks, Dick Tibboel, Suowen Xu, Zheng Gen Jin, Tono Djuwantono, Wei Yan, Maria M Alves, Robert M W Hofstra, Joseph M Miano
Megacystis microcolon intestinal hypoperistalsis syndrome (MMIHS) is a congenital visceral myopathy characterized by severe dilation of the urinary bladder and defective intestinal motility. The genetic basis of MMIHS has been ascribed to spontaneous and autosomal dominant mutations in actin gamma 2 (ACTG2), a smooth muscle contractile gene. However, evidence suggesting a recessive origin of the disease also exists. Using combined homozygosity mapping and whole exome sequencing, a genetically isolated family was found to carry a premature termination codon in Leiomodin1 (LMOD1), a gene preferentially expressed in vascular and visceral smooth muscle cells...
March 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28292838/ethical-issues-in-human-organoid-and-gastruloid-research
#19
Megan Munsie, Insoo Hyun, Jeremy Sugarman
Research involving human organoids and gastruloids involves ethical issues associated with their derivation as well as their current and future uses. These include unique issues related to the extent of maturation that can be achieved in vitro or through chimeric research, as well as fundamental ethical considerations such as those concerning the provenance of human biomaterials and the use of gene-editing technologies. Many of these issues are not specifically addressed by existing ethics oversight mechanisms, but these mechanisms might be easily extended to help ensure that human organoid and related research moves forward in an ethically appropriate manner...
March 15, 2017: Development
https://www.readbyqxmd.com/read/28291770/nrl-knockdown-by-aav-delivered-crispr-cas9-prevents-retinal-degeneration-in-mice
#20
Wenhan Yu, Suddhasil Mookherjee, Vijender Chaitankar, Suja Hiriyanna, Jung-Woong Kim, Matthew Brooks, Yasaman Ataeijannati, Xun Sun, Lijin Dong, Tiansen Li, Anand Swaroop, Zhijian Wu
In retinitis pigmentosa, loss of cone photoreceptors leads to blindness, and preservation of cone function is a major therapeutic goal. However, cone loss is thought to occur as a secondary event resulting from degeneration of rod photoreceptors. Here we report a genome editing approach in which adeno-associated virus (AAV)-mediated CRISPR/Cas9 delivery to postmitotic photoreceptors is used to target the Nrl gene, encoding for Neural retina-specific leucine zipper protein, a rod fate determinant during photoreceptor development...
March 14, 2017: Nature Communications
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