Zalpha-domains: At the intersection between RNA editing and innate immunity

The involvement of A to I RNA editing in antiviral responses was first indicated by the observation of genomic hyper-mutation for several RNA viruses in the course of persistent infections. However, in only a few cases an antiviral role was ever demonstrated and surprisingly, it turns out that ADARs - the RNA editing enzymes - may have a prominent pro-viral role through the modulation/down-regulation of the interferon response. A key role in this regulatory function of RNA editing is played by ADAR1, an interferon inducible RNA editing enzyme. A distinguishing feature of ADAR1, when compared with other ADARs, is the presence of a Z-DNA binding domain, Zalpha. Since the initial discovery of the specific and high affinity binding of Zalpha to CpG repeats in a left-handed helical conformation, other proteins, all related to the interferon response pathway, were shown to have similar domains throughout the vertebrate lineage. What is the biological function of this domain family remains unclear but a significant body of work provides pieces of a puzzle that points to an important role of Zalpha domains in the recognition of foreign nucleic acids in the cytoplasm by the innate immune system. Here we will provide an overview of our knowledge on ADAR1 function in interferon response with emphasis on Zalpha domains.

Outpatient prescription drugs : data collection and editing in the 1996 Medical Expenditure Panel Survey (HC-010A).

"June 2001."

LEFT: a language for editing and formating text,

"Supported in part by contract AT(11-1)-1018 with the U.S. Atomic Energy Commission and the Advanced Research Projects Agency."

Readings in documentary editing : a highly selective list compiled for the NHPRC Institute for the Editing of Historical Documents /

Shipping list no.: 95-0210-P.

Corpus Christianorum 1953-2003 : xenium natalicium : fifty years of scholarly editing /

Includes bibliographical references.

History of grazing; a circular offering suggestions on a technique for compiling data, writing, and editing material for a history of grazing.

Mimeographed.

Newspaper building, application of efficiency to editing, to mechanical production, to circulation and advertising, with cost finding methods, office forms and systems,

Mode of access: Internet.

Services for activities in group editing 'sage'

The project described in this thesis investigates the needs of a group of people working cooperatively in an OSI environment, and recommends tools and services to meet these needs. The project looks specifically at Services for Activities in Group Editing, and is identified as the `SAGE' project. The project uses case studies to identify user requirements and to determine common functionalities for a variety of group editing activities. A prototype is implemented in an X.400 environment to help refine user requirements, as a source of new ideas and to test the proposed functionalities. The conceptual modelling follows current CCITT proposals, but a new classification of group activities is proposed: Informative, Objective and Supportive application groups. It is proposed that each of these application groups have their own Service Agent. Use of this classification allows the possibility of developing three sets of tools which will cover a wide range of group activities, rather than developing tools for individual activities. Group editing is considered to be in the Supportive application group. A set of additional services and tools to support group editing are proposed in the context of the CCITT draft on group communication, X.gc. The proposed services and tools are mapped onto the X.400 series of recommendations, with the Abstract Service Definition of the operational objects defined, along with their associated component files, by extending the X.420 protocol functionality. It is proposed that each of the Informative, Objective and Supportive application groups should be implemented as a modified X.420 inter-personal messaging system.

Towartds Computer-aided Editing of Scientific and Technical Texts

The paper discusses facilities of computer systems for editing scientific and technical texts, which partially automate functions of human editor and thus help the writer to improve text quality. Two experimental systems LINAR and CONUT developed in 90s to control the quality of Russian scientific and technical texts are briefly described; and general principles for designing more powerful editing systems are pointed out. Features of an editing system being now under development are outlined, primarily the underlying linguistic knowledge base and procedures controlling the text.

Development of an Efficient Genome Editing Method by CRISPR/Cas9 in a Fish Cell Line

This project was carried out during CD’s BBSRC Eastbio PIPS placement at Marine Scotland. The authors are grateful to Dr Milena Monte (University of Aberdeen) for help with the FACS analysis. The authors wish to thank Dr Filippo Del Bene (Neuronal Circuit Development, Institut Curie) and Dr Wenbiao Chen (School of Medicine, Vanderbilt University) for the Addgene plasmids, #61051 and #47929, respectively, and Prof. Nancy C. Reich Marshall (Department of Molecular Genetics and Microbiology, Stony Brooks University) for the plasmid pmEGFP-N1.

Development of an Efficient Genome Editing Method by CRISPR/Cas9 in a Fish Cell Line

This project was carried out during CD’s BBSRC Eastbio PIPS placement at Marine Scotland. The authors are grateful to Dr Milena Monte (University of Aberdeen) for help with the FACS analysis. The authors wish to thank Dr Filippo Del Bene (Neuronal Circuit Development, Institut Curie) and Dr Wenbiao Chen (School of Medicine, Vanderbilt University) for the Addgene plasmids, #61051 and #47929, respectively, and Prof. Nancy C. Reich Marshall (Department of Molecular Genetics and Microbiology, Stony Brooks University) for the plasmid pmEGFP-N1.

CRISPR/Cas9-Mediated Gene Editing of ARG1 in Cell Lines and Primary Cells

Arginase 1 deficiency, a urea cycle disorder resulting from an inability of the body to convert arginine into urea, results in hyperargininemia and sporadic episodes of hyperammonemia. Arginase 1 deficiency can lead to a range of developmental disorders and progressive spastic diplegia in children, and current therapeutic options are limited. Clustered regularly interspaced short palindromic repeat (CRISPR) /CRISPR associated protein (Cas) 9 gene editing systems serve as a novel means of treating genetic disorders such as Arginase 1 (ARG1) deficiency, and must be thoroughly examined to determine their curative capabilities. In these experiments numerous guide RNAs and CRISPR/Cas9 systems targeting the ARG1 gene were designed and observed by heteroduplex assay for their targeting capabilities and cleavage efficiencies in multiple cell lines. The CRISPR/Cas9 system utilized in these experiments, along with a panel of guide RNAs targeting various locations in the arginase 1 gene, successfully produced targeted cleavage in HEK293, MCF7, A549, K562, HeLa, and HepG2 cells; however, targeted cleavage in human dermal fibroblasts, blood outgrowth endothelial cells, and induced pluripotent stem cells was not observed. Additionally, a CRISPR/Cas system involving partially inactivated Cas9 was capable of producing targeted DNA cleavage in intron 1 of ARG1, while a Cas protein termed Cpf1 was incapable of producing targeted cleavage. These results indicate a complex set of variables determining the CRISPR/Cas9 systems’ capabilities in the cell lines and primary cells tested. By examining epigenetic factors and alternative CRISPR/Cas9 gene targeting systems, the CRISPR/Cas9 system can be more thoroughly considered in its ability to act as a means towards editing the genome of arginase 1-deficient individuals.