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Mingfeng Cao, Meirong Gao, Deon Ploessl, Cunjiang Song, Zengyi Shao
Scheffersomyces stipitis, renowned for its native xylose-utilizing capacity, has recently demonstrated its potential in producing health-promoting shikimate pathway derivatives. However, its broader application is hampered by the low transformation efficiency and the lack of genetic engineering tools to enable sophisticated genomic manipulations. S. stipitis employees the predominant non-homologous end joining (NHEJ) mechanism for repairing DNA double-strand breaks (DSB), which is less desired due to its incompetence in achieving precise genome editing...
June 19, 2018: Biotechnology Journal
Katia Tarasava, Eun Joong Oh, Carrie A Eckert, Ryan T Gill
In recent years CRISPR-Cas technologies have revolutionized microbial engineering approaches. Genome editing and non-editing applications of various CRISPR-Cas systems have expanded the throughput and scale of engineering efforts, as well as opened up new avenues for manipulating genomes of non-model organisms. As we expand the range of organisms used for biotechnological applications, we need to develop better, more versatile tools for manipulation of these systems. Here we summarize the current advances in microbial gene editing using CRISPR-Cas based tools, and highlight state-of-the-art methods for high-throughput, efficient genome-scale engineering in model organisms Escherichia coli and Saccharomyces cerevisiae...
June 19, 2018: Biotechnology Journal
M A Bakhrebah, M S Nassar, M S Alsuabeyl, W A Zaher, S A Meo
OBJECTIVE: Infectious diseases are one of the prime causes of death worldwide. An innovative sequence specific editing technology "Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)" has been tested on a broad range of microorganisms to target and destroy invading foreign DNA to human cells or tissues. This study aimed to discuss the mechanism and therapeutic usage of CRISPR/Cas9 genome editing technology in the management of various infectious disease pathogens...
June 2018: European Review for Medical and Pharmacological Sciences
William C Lineaweaver
No abstract text is available yet for this article.
June 19, 2018: Annals of Plastic Surgery
Felicity Aiano
No abstract text is available yet for this article.
June 19, 2018: Anthropology & Medicine
Eszter Kapusi, Eva Stöger
The CRISPR/Cas9 system from Streptococcus pyogenes is an increasingly popular tool for genome editing due to its ease of application. Here we demonstrate genomic DNA fragment removal using RNA directed Cas9 nuclease in barley. The high mutation frequency confirms the exceptional efficiency of the system and its suitability for generating loss-of-function mutant lines that may be used in functional genetics approaches to study endomembrane trafficking pathways and posttranslational protein modifications. The generation of doubled haploids from genome edited plants allows the recovery of true breeding lines that are instantly homozygous for the edited alleles...
2018: Methods in Molecular Biology
Ileana Lorenzini, Stephen Moore, Rita Sattler
The molecular process of RNA editing allows changes in RNA transcripts that increase genomic diversity. These highly conserved RNA editing events are catalyzed by a group of enzymes known as adenosine deaminases acting on double-stranded RNA (ADARs). ADARs are necessary for normal development, they bind to over thousands of genes, impact millions of editing sites, and target critical components of the central nervous system (CNS) such as glutamate receptors, serotonin receptors, and potassium channels. Dysfunctional ADARs are known to cause alterations in CNS protein products and therefore play a role in chronic or acute neurodegenerative and psychiatric diseases as well as CNS cancer...
2018: Advances in Neurobiology
Leonard Katz, Yvonne Y Chen, Ramon Gonzalez, Todd C Peterson, Huimin Zhao, Richard H Baltz
Synthetic biology is a logical extension of what has been called recombinant DNA (rDNA) technology or genetic engineering since the 1970s. As rDNA technology has been the driver for the development of a thriving biotechnology industry today, starting with the commercialization of biosynthetic human insulin in the early 1980s, synthetic biology has the potential to take the industry to new heights in the coming years. Synthetic biology advances have been driven by dramatic cost reductions in DNA sequencing and DNA synthesis; by the development of sophisticated tools for genome editing, such as CRISPR/Cas9; and by advances in informatics, computational tools, and infrastructure to facilitate and scale analysis and design...
June 18, 2018: Journal of Industrial Microbiology & Biotechnology
Zhi Miao, Qian Li, Jian Zhao, Peng Wang, Lei Wang, Hong-Peng He, Nan Wang, Hao Zhou, Tong-Cun Zhang, Xue-Gang Luo
OBJECTIVES: To establish stable infliximab-expressing Chinese hamster ovary (CHO) cells with high tolerance to serum-free culture. RESULTS: Bcl-2 antagonist/killer 1 (BAK1), which is a key mediator of the apoptosis pathway, was disrupted, and infliximab, which is a broadly used monoclonal antibody for the treatment of rheumatoid arthritis and other autoimmune diseases, was incorporated into the BAK1 locus of the CHO chromosome using the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas genome-editing technique...
June 18, 2018: Biotechnology Letters
Viola Vultaggio, Luigi Mansi
No abstract text is available yet for this article.
June 18, 2018: European Journal of Nuclear Medicine and Molecular Imaging
Colin W Howden
In this edition of the American Journal of Gastroenterology, Wang and colleagues report the results of an analysis of six different case-control studies examining the relationship between Helicobacter pylori (H. pylori) infection and Barrett's esophagus. They present a cogent argument that there is an inverse association between these two that is mediated via GERD. This is broadly consistent with previous reports. While further establishing this inverse association, the findings should not materially influence our routine clinical practice regarding GERD or H...
June 19, 2018: American Journal of Gastroenterology
Wen Y Wu, Joyce H G Lebbink, Roland Kanaar, Niels Geijsen, John van der Oost
Over the last decade, research on distinct types of CRISPR systems has revealed many structural and functional variations. Recently, several novel types of single-polypeptide CRISPR-associated systems have been discovered including Cas12a/Cpf1 and Cas13a/C2c2. Despite distant similarities to Cas9, these additional systems have unique structural and functional features, providing new opportunities for genome editing applications. Here, relevant fundamental features of natural and engineered CRISPR-Cas variants are compared...
July 2018: Nature Chemical Biology
Sergey V Melnikov, Keith D Rivera, Denis Ostapenko, Arthur Makarenko, Neil D Sanscrainte, James J Becnel, Mark J Solomon, Catherine Texier, Darryl J Pappin, Dieter Söll
Microsporidia are parasitic fungi-like organisms that invade the interior of living cells and cause chronic disorders in a broad range of animals, including humans. These pathogens have the tiniest known genomes among eukaryotic species, for which they serve as a model for exploring the phenomenon of genome reduction in obligate intracellular parasites. Here we report a case study to show an apparent effect of overall genome reduction on the primary structure and activity of aminoacyl-tRNA synthetases, indispensable cellular proteins required for protein synthesis...
June 18, 2018: Proceedings of the National Academy of Sciences of the United States of America
Shalini Nair, Xue Li, Grace A Arya, Marina McDew-White, Marco Ferrari, François Nosten, Tim J C Anderson
Fitness costs are key determinants of whether drug resistance alleles establish and how fast they spread within populations. More than 125 different kelch13 alleles, each containing a different amino acid substitution, have arisen in SE Asian malaria parasite ( Plasmodium falciparum ) populations under artemisinin selection over the past 15 years in a dramatic example of a soft selective event. However, just one of these alleles (C580Y) is now outcompeting other alleles in multiple different countries and is spreading towards fixation...
June 18, 2018: Antimicrobial Agents and Chemotherapy
Takashi Umeyama, Yuta Hayashi, Hisaki Shimosaka, Tatsuya Inukai, Satoshi Yamagoe, Shogo Takatsuka, Yasutaka Hoshino, Minoru Nagi, Shigeki Nakamura, Katsuhiko Kamei, Kenji Ogawa, Yoshitsugu Miyazaki
A pan-azole-resistant Aspergillus fumigatus strain with the cyp51A mutations Gly138Ser and Asn248Lys was isolated from a patient receiving long-term voriconazole treatment. PCR fragments containing cyp51A with the mutations were introduced along with Cas9 protein and single-guide RNA into the azole-resistant/susceptible strains. Recombinant strains showed increased susceptibility via the replacement of Ser138 by glycine. Genetic recombination, which has been hampered thus far in clinical isolates, can now be achieved using Cas9/CRISPR genome editing...
June 18, 2018: Antimicrobial Agents and Chemotherapy
Ning Ma, Joe Zhang, Ilanit Itzhaki, Sophia L Zhang, Haodong Chen, Francois Haddad, Tomoya Kitani, Kitchener D Wilson, Lei Tian, Rajani Shrestha, Haodi Wu, Chi Keung Lam, Nazish Sayed, Joseph C Wu
Background -The progression toward low-cost and rapid next-generation sequencing has uncovered a multitude of variants of uncertain significance (VUS) in both patients and asymptomatic "healthy" individuals. A VUS is a rare or novel variant for which disease pathogenicity has not been conclusively demonstrated or excluded, and thus cannot be definitively annotated. VUS, therefore, pose critical clinical interpretation and risk-assessment challenges, and new methods are urgently needed to better characterize their pathogenicity...
June 18, 2018: Circulation
William S DeWitt, Krystle K Q Yu, Damien B Wilburn, Anna Sherwood, Marissa Vignali, Cheryl L Day, Thomas J Scriba, Harlan S Robins, Willie J Swanson, Ryan O Emerson, Philip H Bradley, Chetan Seshadri
Human T cells that recognize lipid Ags presented by highly conserved CD1 proteins often express semi-invariant TCRs, but the true diversity of lipid Ag-specific TCRs remains unknown. We use CD1b tetramers and high-throughput immunosequencing to analyze thousands of TCRs from ex vivo-sorted or in vitro-expanded T cells specific for the mycobacterial lipid Ag, glucose monomycolate. Our results reveal a surprisingly diverse repertoire resulting from editing of germline-encoded gene rearrangements analogous to MHC-restricted TCRs...
June 18, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
D Caputo, M Cartillone, C Cascone, D Pozzi, L Digiacomo, S Palchetti, G Caracciolo, R Coppola
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) early diagnosis is  crucial  and new, cheap and user-friendly techniques for biomarker identification  are  needed. "Protein corona" (PC) is emerging a new bio-interface potentially useful in tumor early diagnosis. In a previous investigation, we showed that relevant differences between the  protein patterns of  PCs formed on lipid NPs after exposure to PDAC and non-cancer plasma  samples exist. To extend that research, We performed this pilot study to investigate the effect of PDAC tumor size and distant metastases on PC composition...
June 12, 2018: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
Yves Quentin, Patricia Siguier, Mick Chandler, Gwennaele Fichant
BACKGROUND: Some mobile genetic elements target the lagging strand template during DNA replication. Bacterial examples are insertion sequences IS608 and ISDra2 (IS200/IS605 family members). They use obligatory single-stranded circular DNA intermediates for excision and insertion and encode a transposase, TnpAIS200 , which recognizes subterminal secondary structures at the insertion sequence ends. Similar secondary structures, Repeated Extragenic Palindromes (REP), are present in many bacterial genomes...
June 19, 2018: BMC Genomics
David M Franzen
No abstract text is available yet for this article.
June 2018: Journal of Pastoral Care & Counseling: JPCC
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