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https://www.readbyqxmd.com/read/28731685/lipophilic-polycation-vehicles-display-high-plasmid-dna-delivery-to-multiple-cell-types
#1
Yaoying Wu, Adam E Smith, Theresa M Reineke
A class of cationic poly(alkylamidoamine)s (PAAAs) containing lipophilic methylene linkers were designed and examined as in vitro plasmid DNA (pDNA) delivery agents. The PAAAs were synthesized via step-growth polymerization between a diamine monomer and each of four different diacid chloride monomers with varying methylene linker lengths, including glutaryl chloride, adipoyl chloride, pimeloyl chloride, and suberoyl chloride, which served to systematically increase the lipophilicity of the polymers. The synthesized polymers successfully complexed with pDNA in reduced serum medium at N/P ratios of 5 and greater, resulting in polyplexes with hydrodynamic diameters of approximately 1 μm...
July 21, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28729683/a-positive-feedback-loop-mediated-by-sigma-x-enhances-expression-of-the-streptococcal-regulator-comr
#2
Rabia Khan, Roger Junges, Heidi A Åmdal, Tsute Chen, Donald A Morrison, Fernanda C Petersen
Natural transformation is used by bacteria to take up DNA from their surroundings and incorporate it into their genomes. Streptococci do so during a transient period of competence, triggered by pheromones that they produce, secrete and sense under conditions influenced by the environment. In Streptococcus mutans, Streptococcus suis, and species of the bovis, salivarius and pyogenic groups of streptococci, the pheromone XIP is sensed by the intra-cellular regulator ComR, that in turn activates the transcription of comS, encoding the XIP precursor, and of sigX, encoding the only known alternative sigma factor in streptococci...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28729655/a-crispr-cas9-guidance-rna-screen-platform-for-hiv-provirus-disruption-and-hiv-aids-gene-therapy-in-astrocytes
#3
Zaohua Huang, Madahavan Nair
HIV/AIDS remains a major health threat despite significant advances in the prevention and treatment of HIV infection. The major reason is the inability of existing treatments to eradicate the multiple HIV reservoirs in the human body, including astrocytes in the human brain. CRISPR/Cas9 system is an emerging gene-editing technique with the potential to eliminate or disrupt HIV provirus in HIV reservoir cells, which may lead to a complete cure of HIV/AIDS. The key components of CRISPR/Cas9 are guide RNAs (gRNAs) which determine specific sequence targeting of DNAs...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28729543/evaluation-of-atm-heterozygous-mutations-underlying-individual-differences-in-radiosensitivity-using-genome-editing-in-human-cultured-cells
#4
Ekaterina Royba, Tatsuo Miyamoto, Silvia Natsuko Akutsu, Kosuke Hosoba, Hiroshi Tauchi, Yoshiki Kudo, Satoshi Tashiro, Takashi Yamamoto, Shinya Matsuura
Ionizing radiation (IR) induces DNA double-strand breaks (DSBs), which are an initial step towards chromosomal aberrations and cell death. It has been suggested that there are individual differences in radiosensitivity within human populations, and that the variations in DNA repair genes might determine this heterogeneity. However, it is difficult to quantify the effect of genetic variants on the individual differences in radiosensitivity, since confounding factors such as smoking and the diverse genetic backgrounds within human populations affect radiosensitivity...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28727142/genomic-and-transcriptomic-heterogeneity-of-colorectal-tumors-arising-in-lynch-syndrome
#5
Hans Binder, Lydia Hopp, Michal R Schweiger, Steve Hoffmann, Frank Jühling, Martin Kerick, Bernd Timmermann, Susann Siebert, Christina Grimm, Lilit Nersisyan, Arsen Arakelyan, Maria Herberg, Peter Buske, Henry Loeffler-Wirth, Maciej Rosolowski, Christoph Engel, Jens Przybilla, Martin Peifer, Nicolaus Friedrichs, Gabriela Moeslein, Margarete Odenthal, Michelle Hussong, Sophia Peters, Stefanie Holzapfel, Jacob Nattermann, Robert Hueneburg, Wolff Schmiegel, Brigitte Royer-Pokora, Stefan Aretz, Michael Kloth, Matthias Kloor, Reinhard Buettner, Jörg Galle, Markus Loeffler
Colorectal cancer (CRC) arising in Lynch Syndrome (LS) comprises tumors with constitutional mutations in DNA mismatch-repair genes. Whole-genome and transcriptome studies of LS-CRC are still missing to address questions about similarities and differences of mutation and gene expression characteristics between LS-CRC and sporadic CRC, about the molecular heterogeneity of LS-CRC and about specific mechanisms of LS-CRC genesis linked to dysfunctional mismatch-repair in LS colonic mucosa and the possible role of immune editing...
July 20, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28726008/the-trouble-with-collective-nouns-for-genome-editing
#6
Sara Wells, Jean Stéphane Joly
We should start as we mean to go on and try to avoid the confusion most of us experience when bombarded with acronyms with overstated significations. You will be familiar with the situation, you are in a seminar or a meeting and someone who has been using a set of acronyms for years, includes them in sentence after sentence that has you lost because you don't know what some or most of them stand for. Even worse when scientists start making verbs out of them, CRISPR seems to have fallen into this category; how many of us have heard someone asking if a mutation can be CRISPRed! Does it matter though? We are all familiar with informal language in scientific talks and discussions which is replaced by more formal dialect when research is published or presented to the general public...
July 18, 2017: Mammalian Genome: Official Journal of the International Mammalian Genome Society
https://www.readbyqxmd.com/read/28725950/genome-editing-and-assisted-reproduction-curing-embryos-society-or-prospective-parents
#7
Giulia Cavaliere
This paper explores the ethics of introducing genome-editing technologies as a new reproductive option. In particular, it focuses on whether genome editing can be considered a morally valuable alternative to preimplantation genetic diagnosis (PGD). Two arguments against the use of genome editing in reproduction are analysed, namely safety concerns and germline modification. These arguments are then contrasted with arguments in favour of genome editing, in particular with the argument of the child's welfare and the argument of parental reproductive autonomy...
July 19, 2017: Medicine, Health Care, and Philosophy
https://www.readbyqxmd.com/read/28725345/genome-editing-is-revolutionizing-biology
#8
EDITORIAL
Yiping Qi
No abstract text is available yet for this article.
2017: Cell & Bioscience
https://www.readbyqxmd.com/read/28725230/genetics-and-genomics-of-cotton-leaf-curl-disease-its-viral-causal-agents-and-whitefly-vector-a-way-forward-to-sustain-cotton-fiber-security
#9
REVIEW
Mehboob-Ur- Rahman, Ali Q Khan, Zainab Rahmat, Muhammad A Iqbal, Yusuf Zafar
Cotton leaf curl disease (CLCuD) after its first epidemic in 1912 in Nigeria, has spread to different cotton growing countries including United States, Pakistan, India, and China. The disease is of viral origin-transmitted by the whitefly Bemisia tabaci, which is difficult to control because of the prevalence of multiple virulent viral strains or related species. The problem is further complicated as the CLCuD causing virus complex has a higher recombination rate. The availability of alternate host crops like tomato, okra, etc...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28724960/sgrna-expression-of-cripsr-cas9-system-based-on-mirna-polycistrons-as-a-versatile-tool-to-manipulate-multiple-and-tissue-specific-genome-editing
#10
Chen Xie, Yan-Lian Chen, Dong-Fang Wang, Yi-Lin Wang, Tian-Peng Zhang, Hui Li, Fu Liang, Yong Zhao, Guang-Ya Zhang
CRISPR/Cas9-mediated genome editing is a next-generation strategy for genetic modifications. Typically, sgRNA is constitutively expressed relying on RNA polymerase III promoters. Polymerase II promoters initiate transcription in a flexible manner, but sgRNAs generated by RNA polymerase II promoter lost their nuclease activity. To express sgRNAs in a tissue-specific fashion and endow CRISPR with more versatile function, a novel system was established in a polycistron, where miRNAs (or shRNAs) and sgRNAs alternately emerged and co-expressed under the control of a single polymerase II promoter...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28724787/disrupted-apical-exocytosis-of-cargo-vesicles-causes-enteropathy-in-fhl5-patients-with-munc18-2-mutations
#11
Georg F Vogel, Jorik M van Rijn, Iris M Krainer, Andreas R Janecke, Carsten Posovzsky, Marta Cohen, Claire Searle, Prevost Jantchou, Johanna C Escher, Natalie Patey, Ernest Cutz, Thomas Müller, Sabine Middendorp, Michael W Hess, Lukas A Huber
Familial hemophagocytic lymphohistiocytosis 5 (FHL5) is an autosomal recessive disease caused by mutations in STXBP2, coding for Munc18-2, which is required for SNARE-mediated membrane fusion. FHL5 causes hematologic and gastrointestinal symptoms characterized by chronic enteropathy that is reminiscent of microvillus inclusion disease (MVID). However, the molecular pathophysiology of FHL5-associated diarrhea is poorly understood. Five FHL5 patients, including four previously unreported patients, were studied...
July 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28723946/the-mitochondrial-genome-of-the-terrestrial-carnivorous-plant-utricularia-reniformis-lentibulariaceae-structure-comparative-analysis-and-evolutionary-landmarks
#12
Saura R Silva, Danillo O Alvarenga, Yani Aranguren, Helen A Penha, Camila C Fernandes, Daniel G Pinheiro, Marcos T Oliveira, Todd P Michael, Vitor F O Miranda, Alessandro M Varani
The carnivorous plants of the family Lentibulariaceae have attained recent attention not only because of their interesting lifestyle, but also because of their dynamic nuclear genome size. Lentibulariaceae genomes span an order of magnitude and include species with the smallest genomes in angiosperms, making them a powerful system to study the mechanisms of genome expansion and contraction. However, little is known about mitochondrial DNA (mtDNA) sequences of this family, and the evolutionary forces that shape this organellar genome...
2017: PloS One
https://www.readbyqxmd.com/read/28723893/in-vivo-crispr-screening-identifies-ptpn2-as-a-cancer-immunotherapy-target
#13
Robert T Manguso, Hans W Pope, Margaret D Zimmer, Flavian D Brown, Kathleen B Yates, Brian C Miller, Natalie B Collins, Kevin Bi, Martin W LaFleur, Vikram R Juneja, Sarah A Weiss, Jennifer Lo, David E Fisher, Diana Miao, Eliezer Van Allen, David E Root, Arlene H Sharpe, John G Doench, W Nicholas Haining
Immunotherapy with PD-1 checkpoint blockade is effective in only a minority of patients with cancer, suggesting that additional treatment strategies are needed. Here we use a pooled in vivo genetic screening approach using CRISPR-Cas9 genome editing in transplantable tumours in mice treated with immunotherapy to discover previously undescribed immunotherapy targets. We tested 2,368 genes expressed by melanoma cells to identify those that synergize with or cause resistance to checkpoint blockade. We recovered the known immune evasion molecules PD-L1 and CD47, and confirmed that defects in interferon-γ signalling caused resistance to immunotherapy...
July 19, 2017: Nature
https://www.readbyqxmd.com/read/28723575/crispr-mediated-integration-of-large-gene-cassettes-using-aav-donor-vectors
#14
Rasmus O Bak, Matthew H Porteus
The CRISPR/Cas9 system has recently been shown to facilitate high levels of precise genome editing using adeno-associated viral (AAV) vectors to serve as donor template DNA during homologous recombination (HR). However, the maximum AAV packaging capacity of ∼4.5 kb limits the donor size. Here, we overcome this constraint by showing that two co-transduced AAV vectors can serve as donors during consecutive HR events for the integration of large transgenes. Importantly, the method involves a single-step procedure applicable to primary cells with relevance to therapeutic genome editing...
July 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28720816/functional-divergence-and-origin-of-the-dag-like-gene-family-in-plants
#15
Meijie Luo, Manjun Cai, Jianhua Zhang, Yurong Li, Ruyang Zhang, Wei Song, Ke Zhang, Hailin Xiao, Bing Yue, Yonglian Zheng, Yanxin Zhao, Jiuran Zhao, Fazhan Qiu
The nuclear-encoded DAG-like (DAL) gene family plays critical roles in organelle C-to-U RNA editing in Arabidopsis thaliana. However, the origin, diversification and functional divergence of DAL genes remain unclear. Here, we analyzed the genomes of diverse plant species and found that: DAL genes are specific to spermatophytes, all DAL genes share a conserved gene structure and protein similarity with the inhibitor I9 domain of subtilisin genes found in ferns and mosses, suggesting that DAL genes likely arose from I9-containing proproteases via exon shuffling...
July 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28720717/sting-is-an-essential-mediator-of-the-ku70-mediated-production-of-ifn-%C3%AE-1-in-response-to-exogenous-dna
#16
Hongyan Sui, Ming Zhou, Hiromi Imamichi, Xiaoli Jiao, Brad T Sherman, H Clifford Lane, Tomozumi Imamichi
We previously identified Ku70, a subunit of a DNA repair protein complex, as a cytosolic DNA sensor that induces the production of interferon-λ1 (IFN-λ1) by human primary cells and cell lines. IFN-λ1 is a type III IFN and has similar antiviral activity to that of the type I IFNs (IFN-α and IFN-β). We observed that human embryonic kidney (HEK) 293T cells, which are deficient in the innate immune adaptor protein STING (stimulator of IFN genes), did not produce IFN-λ1 in response to DNA unless they were reconstituted with STING...
July 18, 2017: Science Signaling
https://www.readbyqxmd.com/read/28720677/synthetic-circulating-cell-free-dna-as-quality-control-materials-for-somatic-mutation-detection-in-liquid-biopsy-for-cancer
#17
Rui Zhang, Rongxue Peng, Ziyang Li, Peng Gao, Shiyu Jia, Xin Yang, Jiansheng Ding, Yanxi Han, Jiehong Xie, Jinming Li
BACKGROUND: Detection of somatic genomic alterations in tumor-derived cell-free DNA (cfDNA) in the plasma is challenging owing to the low concentrations of cfDNA, variable detection methods, and complex workflows. Moreover, no proper quality control materials are available currently. METHODS: We developed a set of synthetic cfDNA quality control materials (SCQCMs) containing spike-in cfDNA on the basis of micrococcal nuclease digestion carrying somatic mutations as simulated cfDNA and matched genomic DNA as genetic background to emulate paired tumor-normal samples in real clinical tests...
July 18, 2017: Clinical Chemistry
https://www.readbyqxmd.com/read/28719630/oligo-and-dsdna-mediated-genome-editing-using-a-teta-dual-selection-system-in-escherichia-coli
#18
Young Shin Ryu, Sathesh-Prabu Chandran, Kyungchul Kim, Sung Kuk Lee
The ability to precisely and seamlessly modify a target genome is needed for metabolic engineering and synthetic biology techniques aimed at creating potent biosystems. Herein, we report on a promising method in Escherichia coli that relies on the insertion of an optimized tetA dual selection cassette followed by replacement of the same cassette with short, single-stranded DNA (oligos) or long, double-stranded DNA and the isolation of recombinant strains by negative selection using NiCl2. This method could be rapidly and successfully used for genome engineering, including deletions, insertions, replacements, and point mutations, without inactivation of the methyl-directed mismatch repair (MMR) system and plasmid cloning...
2017: PloS One
https://www.readbyqxmd.com/read/28718902/pluripotent-stem-cell-based-platforms-in-cardiac-disease-modeling-and-drug-testing
#19
N Shaheen, A Shiti, L Gepstein
The ability to generate patient/disease-specific human pluripotent stem cell (hPSC)-derived cardiomyocytes (hPSC-CMs) brings a unique value to the fields of cardiac disease modeling, drug testing, drug discovery, and precision medicine. Further integration of emerging innovative technologies such as developmental-biology inspired differentiation into chamber-specific cardiomyocyte subtypes, genome-editing, tissue-engineering, and novel functional phenotyping methodologies should facilitate even more advanced investigations...
August 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28718799/zebrafish-as-a-model-organism-for-the-development-of-drugs-for-skin-cancer
#20
REVIEW
Fatemeh Bootorabi, Hamed Manouchehri, Reza Changizi, Harlan Barker, Elisabetta Palazzo, Annalisa Saltari, Mataleena Parikka, Carlo Pincelli, Ashok Aspatwar
Skin cancer, which includes melanoma and squamous cell carcinoma, represents the most common type of cutaneous malignancy worldwide, and its incidence is expected to rise in the near future. This condition derives from acquired genetic dysregulation of signaling pathways involved in the proliferation and apoptosis of skin cells. The development of animal models has allowed a better understanding of these pathomechanisms, with the possibility of carrying out toxicological screening and drug development. In particular, the zebrafish (Danio rerio) has been established as one of the most important model organisms for cancer research...
July 18, 2017: International Journal of Molecular Sciences
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