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https://www.readbyqxmd.com/read/28815975/urea-based-recirculation-validation-of-the-symmetrical-palindrome-catheter
#1
Martin Jonczyk, Christian Althoff, Torsten Slowinski, Ina Lieker, Marcel Naik, Jonas Auer, Raúl García Marcos, Ejona Duka, Bernd Hamm, Maximilian de Bucourt
BACKGROUND: High blood flow and low recirculation rates are central for adequate haemodialysis. A new symmetrical tip has been invented promising efficient haemodialysis even if the ports are reversed. OBJECTIVE: To evaluate access recirculation of the 'palindrome' catheter and to report initial experiences in a clinical setting. MATERIAL AND METHODS: After implantation of the new catheter in 20 patients (male: 14; female: 6; mean age 72 ± 12...
August 16, 2017: Journal of Renal Care
https://www.readbyqxmd.com/read/28815851/basics-of-genome-editing-technology-and-its-application-in-livestock-species
#2
REVIEW
Bjoern Petersen
In the last decade, the research community has witnessed a blooming of targeted genome editing tools and applications. Novel programmable DNA nucleases such as zinc finger nucleases (ZFNs), transcription activator-like endonucleases (TALENs) and the clustered regularly interspaced short palindromic repeats/Cas9 system (CRISPR/Cas9) possess long recognition sites and are capable of cutting DNA in a very specific manner. These DNA nucleases mediate targeted genetic alterations by enhancing the DNA mutation rate via induction of double-strand breaks at a predetermined genomic site...
August 2017: Reproduction in Domestic Animals, Zuchthygiene
https://www.readbyqxmd.com/read/28815492/building-cre-knockin-rat-lines-using-crispr-cas9
#3
Yuanwu Ma, Lianfeng Zhang, Xingxu Huang
Conditional gene inactivation strategy helps researchers to study the gene functions that are critical in embryogenesis or in defined tissues of adulthood. The Cre/loxP system is widely used for conditional gene inactivation/activation in cells or organisms. Cre knockin animal lines are essential for gene expression or inactivation in a spatially and temporally restricted manner. However, to generate a Cre knockin line by traditional approach is laborious. Recently, the clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9 (CRISPR/Cas9) has been proven as a simple and efficient genome-editing tool...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28809766/crispr-cas9-editing-of-nf1-gene-identifies-crmp2-as-a-therapeutic-target-in-neurofibromatosis-type-1-nf1-related-pain-that-is-reversed-by-s-lacosamide
#4
Aubin Moutal, Xiaofang Yang, Wennan Li, Kerry B Gilbraith, Shizhen Luo, Song Cai, Liberty François-Moutal, Lindsey A Chew, Seul Ki Yeon, Shreya S Bellampalli, Chaoling Qu, Jennifer Y Xie, Mohab M Ibrahim, May Khanna, Ki Duk Park, Frank Porreca, Rajesh Khanna
Neurofibromatosis type 1 (NF1) is a rare autosomal dominant disease linked to mutations of the Nf1 gene. NF1 patients commonly experience severe pain. Studies on mice with Nf1 haploinsufficiency have been instructive in identifying sensitization of ion channels as a possible cause underlying the heightened pain suffered by NF1 patients. However, behavioral assessments of Nf1+/- mice have led to uncertain conclusions about the potential causal role of Nf1 in pain. We used the clustered regularly interspaced short palindromic repeats/(CRISPR)-associated 9 (CRISPR/Cas9) genome editing system to create and mechanistically characterize a novel rat model of NF1-related pain...
July 3, 2017: Pain
https://www.readbyqxmd.com/read/28806273/the-changing-landscape-of-gene-editing-in-hematopoietic-stem-cells-a-step-towards-cas9-clinical-translation
#5
Daniel P Dever, Matthew H Porteus
PURPOSE OF REVIEW: Since the discovery two decades ago that programmable endonucleases can be engineered to modify human cells at single nucleotide resolution, the concept of genome editing was born. Now these technologies are being applied to therapeutically relevant cell types, including hematopoietic stem cells (HSC), which possess the power to repopulate an entire blood and immune system. The purpose of this review is to discuss the changing landscape of genome editing in hematopoietic stem cells (GE-HSC) from the discovery stage to the preclinical stage, with the imminent goal of clinical translation for the treatment of serious genetic diseases of the blood and immune system...
August 12, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28802668/two-novel-lncrnas-discovered-in-human-mitochondrial-dna-using-pacbio-full-length-transcriptome-data
#6
Shan Gao, Xiaoxuan Tian, Hong Chang, Yu Sun, Zhenfeng Wu, Zhi Cheng, Pengzhi Dong, Qiang Zhao, Jishou Ruan, Wenjun Bu
In this study, we introduced a general framework to use PacBio full-length transcriptome sequencing for the investigation of mitochondrial RNAs. As a result, we produced the first full-length human mitochondrial transcriptome based on the public PacBio data and characterized the human mitochondrial transcriptome with more comprehensive and accurate information. Other results included the determination of the H-strand primary transcript, the identification of ND5/ND6AS/tRNA(Glu)AS, the discovery of palindrome small RNAs and the construction of "cleavage" model...
August 9, 2017: Mitochondrion
https://www.readbyqxmd.com/read/28801311/ethical-issues-when-modelling-brain-disorders-in-non-human-primates
#7
Carolyn P Neuhaus
Non-human animal models of human diseases advance our knowledge of the genetic underpinnings of disease and lead to the development of novel therapies for humans. While mice are the most common model organisms, their usefulness is limited. Larger animals may provide more accurate and valuable disease models, but it has, until recently, been challenging to create large animal disease models. Genome editors, such as Clustered Randomised Interspersed Palindromic Repeat (CRISPR), meet some of these challenges and bring routine genome engineering of larger animals and non-human primates (NHPs) well within reach...
August 11, 2017: Journal of Medical Ethics
https://www.readbyqxmd.com/read/28800585/comparative-pathogenomics-of-clostridium-tetani
#8
Jonathan E Cohen, Rong Wang, Rong-Fong Shen, Wells W Wu, James E Keller
Clostridium tetani and Clostridium botulinum produce two of the most potent neurotoxins known, tetanus neurotoxin and botulinum neurotoxin, respectively. Extensive biochemical and genetic investigation has been devoted to identifying and characterizing various C. botulinum strains. Less effort has been focused on studying C. tetani likely because recently sequenced strains of C. tetani show much less genetic diversity than C. botulinum strains and because widespread vaccination efforts have reduced the public health threat from tetanus...
2017: PloS One
https://www.readbyqxmd.com/read/28798304/comparison-of-pathogenicity-related-genes-in-the-current-pseudorabies-virus-outbreak-in-china
#9
Yan-Dong Tang, Ji-Ting Liu, Tong-Yun Wang, Ming-Xia Sun, Zhi-Jun Tian, Xue-Hui Cai
There is currently a pandemic of pseudorabies virus (PRV) variant strains in China. Despite extensive research on PRV variant strains in the past two years, few studies have investigated PRV pathogenicity-related genes. To determine which gene(s) is/are linked to PRV virulence, ten putative virulence genes were knocked out using clustered regularly interspaced palindromic repeats (CRISPR)/Cas9 technology. The pathogenicity of these mutants was evaluated in a mouse model. Our results demonstrated that of the ten tested genes, the thymidine kinase (TK) and glycoprotein M (gM) knockout mutants displayed significantly reduced virulence...
August 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28792876/nad-deficiency-congenital-malformations-and-niacin-supplementation
#10
Hongjun Shi, Annabelle Enriquez, Melissa Rapadas, Ella M M A Martin, Roni Wang, Julie Moreau, Chai K Lim, Justin O Szot, Eddie Ip, James N Hughes, Kotaro Sugimoto, David T Humphreys, Aideen M McInerney-Leo, Paul J Leo, Ghassan J Maghzal, Jake Halliday, Janine Smith, Alison Colley, Paul R Mark, Felicity Collins, David O Sillence, David S Winlaw, Joshua W K Ho, Gilles J Guillemin, Matthew A Brown, Kazu Kikuchi, Paul Q Thomas, Roland Stocker, Eleni Giannoulatou, Gavin Chapman, Emma L Duncan, Duncan B Sparrow, Sally L Dunwoodie
BACKGROUND: Congenital malformations can be manifested as combinations of phenotypes that co-occur more often than expected by chance. In many such cases, it has proved difficult to identify a genetic cause. We sought the genetic cause of cardiac, vertebral, and renal defects, among others, in unrelated patients. METHODS: We used genomic sequencing to identify potentially pathogenic gene variants in families in which a person had multiple congenital malformations...
August 10, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28790199/in-vivo-genome-editing-restores-dystrophin-expression-and-cardiac-function-in-dystrophic-mice
#11
Mona El Refaey, Li Xu, Yandi Gao, Benjamin D Canan, Tm A Adesanya, Sarah C Warner, Keiko Akagi, David E Symer, Peter J Mohler, Jianjie Ma, Paul M Janssen, Renzhi Han
Rationale: Duchenne muscular dystrophy (DMD) is a severe inherited form of muscular dystrophy caused by mutations in the reading frame of the dystrophin gene disrupting its protein expression. Dystrophic cardiomyopathy is a leading cause of death in DMD patients and currently no effective treatment exists to halt its progression. Recent advancement in genome editing technologies offers a promising therapeutic approach in restoring dystrophin protein expression. However, the impact of this approach on DMD cardiac function has yet to be evaluated...
August 8, 2017: Circulation Research
https://www.readbyqxmd.com/read/28783550/characterization-of-the-clustered-regularly-interspaced-short-palindromic-repeats-sites-in-streptococcus-mutans-isolated-from-early-childhood-caries-patients
#12
Jing Chen, Tiancheng Li, Xuedong Zhou, Lei Cheng, Yuanyuan Huo, Jing Zou, Yuqing Li
OBJECTIVE: The aim of this study was to analyze the characteristics of the clustered regularly interspaced short palindromic repeats (CRISPR) sites in 45 clinical Streptococcus mutans strains and their relationship to the clinical manifestations of early childhood caries (ECC). METHODS: Forty-five S. mutans strains were isolated from the plaque samples taken from sixty-three children. CRISPR sites were sequenced and BLAST was used to compare these sites to those in the CRISPRTarget database...
July 29, 2017: Archives of Oral Biology
https://www.readbyqxmd.com/read/28782493/big-data-and-genome-editing-technology-a-new-paradigm-of-cardiovascular-genomics
#13
Chayakrit Krittanawong, Tao Sun, Eyal Herzog
Cardiovascular diseases (CVDs) encompasse a range of conditions extending from congenital heart disease to acute coronary syndrome most of which are heterogenous in nature and some of them are multiple genetic loci. However, the pathogenesis of most CVDs remains incompletely understood. The advance in genome-editing technologies, an engineering process of DNA sequences at precise genomic locations, has enabled a new paradigm that human genome can be precisely modified to achieve a therapeutic effect. Genome-editing includes the correction of genetic variants that cause disease, the addition of therapeutic genes to specific sites in the genomic locations, and the removal of deleterious genes or genome sequences...
August 4, 2017: Current Cardiology Reviews
https://www.readbyqxmd.com/read/28771535/association-between-periodontitis-and-the-risk-of-palindromic-rheumatism-a-nationwide-population-based-case-control-study
#14
Ching-Heng Lin, Der-Yuan Chen, Wen-Cheng Chao, Tsai-Ling Liao, Yi-Ming Chen, Hsin-Hua Chen
OBJECTIVE: To estimate the association between a history of periodontitis (PD) and the risk of incident palindromic rheumatism (PR). METHODS: Using a nationwide, administrative database, this study identified 4,421 newly-diagnosed PR cases from 2007 to 2012 and randomly selected 44,210 non-PR controls matched (1:10) for sex, age and the year of the index date. After adjusting for comorbid diabetes mellitus, we estimated the odds ratios (ORs) with 95% confidence intervals (CIs) using conditional logistic regression analysis to quantify the association between a history of PD and the risk of PR...
2017: PloS One
https://www.readbyqxmd.com/read/28769116/the-reverse-transcriptases-associated-with-crispr-cas-systems
#15
Nicolás Toro, Francisco Martínez-Abarca, Alejandro González-Delgado
CRISPR (clustered regularly interspaced short palindromic repeats) and associated proteins (Cas) act as adaptive immune systems in bacteria and archaea. Some CRISPR-Cas systems have been found to be associated with putative reverse transcriptases (RT), and an RT-Cas1 fusion associated with a type III-B system has been shown to acquire RNA spacers in vivo. Nevertheless, the origin and evolutionary relationships of these RTs and associated CRISPR-Cas systems remain largely unknown. We performed a comprehensive phylogenetic analysis of these RTs and associated Cas1 proteins, and classified their CRISPR-Cas modules...
August 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28768804/synergistic-action-of-the-mcl-1-inhibitor-s63845-with-current-therapies-in-preclinical-models-of-triple-negative-and-her2-amplified-breast-cancer
#16
Delphine Merino, James R Whittle, François Vaillant, Antonin Serrano, Jia-Nan Gong, Goknur Giner, Ana Leticia Maragno, Maïa Chanrion, Emilie Schneider, Bhupinder Pal, Xiang Li, Grant Dewson, Julius Gräsel, Kevin Liu, Najoua Lalaoui, David Segal, Marco J Herold, David C S Huang, Gordon K Smyth, Olivier Geneste, Guillaume Lessene, Jane E Visvader, Geoffrey J Lindeman
The development of BH3 mimetics, which antagonize prosurvival proteins of the BCL-2 family, represents a potential breakthrough in cancer therapy. Targeting the prosurvival member MCL-1 has been an area of intense interest because it is frequently deregulated in cancer. In breast cancer, MCL-1 is often amplified, and high expression predicts poor patient outcome. We tested the MCL-1 inhibitor S63845 in breast cancer cell lines and patient-derived xenografts with high expression of MCL-1. S63845 displayed synergistic activity with docetaxel in triple-negative breast cancer and with trastuzumab or lapatinib in HER2-amplified breast cancer...
August 2, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28765632/efficient-increase-of-%C3%A9-aminobutyric-acid-gaba-content-in-tomato-fruits-by-targeted-mutagenesis
#17
Satoko Nonaka, Chikako Arai, Mariko Takayama, Chiaki Matsukura, Hiroshi Ezura
γ-Aminobutyric acid (GABA) is a non-proteinogenic amino acid that has hypotensive effects. Tomato (Solanum lycopersicum L.) is among the most widely cultivated and consumed vegetables in the world and contains higher levels of GABA than other major crops. Increasing these levels can further enhance the blood pressure-lowering function of tomato fruit. Glutamate decarboxylase (GAD) is a key enzyme in GABA biosynthesis; it has a C-terminal autoinhibitory domain that regulates enzymatic function, and deleting this domain increases GAD activity...
August 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28765283/heme-and-nitric-oxide-binding-by-the-transcriptional-regulator-dnrf-from-the-marine-bacterium-dinoroseobacter-shibae-increases-napd-promoter-affinity
#18
Matthias Ebert, Peter Schweyen, Martin Br Oumlring, Sebastian Laass, Elisabeth H Aumlrtig, Dieter Jahn
Under oxygen-limiting conditions, the marine bacterium Dinoroseobacter shibae DFL12(T) generates energy via denitrification, a respiratory process in which nitric oxide (NO) is an intermediate. Accumulation of NO may cause cytotoxic effects. The response to this nitrosative (NO-triggered) stress is controlled by the Crp/Fnr-type transcriptional regulator DnrF. We analyzed the response to NO and the mechanism of NO sensing by the DnrF regulator. Using reporter gene fusions and transcriptomics, here we report that DnrF selectively repressed nitrate reductase (nap) genes, preventing further NO formation...
August 1, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28763486/comparative-analysis-of-complete-plastid-genomes-from-wild-soybean-glycine-soja-and-nine-other-glycine-species
#19
Sajjad Asaf, Abdul Latif Khan, Muhammad Aaqil Khan, Qari Muhammad Imran, Sang-Mo Kang, Khdija Al-Hosni, Eun Ju Jeong, Ko Eun Lee, In-Jung Lee
The plastid genomes of different plant species exhibit significant variation, thereby providing valuable markers for exploring evolutionary relationships and population genetics. Glycine soja (wild soybean) is recognized as the wild ancestor of cultivated soybean (G. max), representing a valuable genetic resource for soybean breeding programmes. In the present study, the complete plastid genome of G. soja was sequenced using Illumina paired-end sequencing and then compared it for the first time with previously reported plastid genome sequences from nine other Glycine species...
2017: PloS One
https://www.readbyqxmd.com/read/28762506/towards-crispr-cas-crops-bringing-together-genomics-and-genome-editing
#20
REVIEW
Armin Scheben, Felix Wolter, Jacqueline Batley, Holger Puchta, David Edwards
I. II. III. IV. V. VI. VII. VIII. References SUMMARY: With the rapid increase in the global population and the impact of climate change on agriculture, there is a need for crops with higher yields and greater tolerance to abiotic stress. However, traditional crop improvement via genetic recombination or random mutagenesis is a laborious process and cannot keep pace with increasing crop demand. Genome editing technologies such as clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein (CRISPR/Cas) allow targeted modification of almost any crop genome sequence to generate novel variation and accelerate breeding efforts...
August 1, 2017: New Phytologist
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