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https://www.readbyqxmd.com/read/28088640/bioethanol-production-from-cellulosic-hydrolysates-by-engineered-industrial-saccharomyces-cerevisiae
#1
Ye-Gi Lee, Yong-Su Jin, Young-Lok Cha, Jin-Ho Seo
Even though industrial yeast strains exhibit numerous advantageous traits for the production of bioethanol, their genetic manipulation has been limited. This study demonstrates that an industrial polyploidy Saccharomyces cerevisiae JHS200 can be engineered through Cas9 (CRISPR associated protein 9)-based genome editing. Specifically, we generated auxotrophic mutants and introduced a xylose metabolic pathway into the auxotrophic mutants. As expected, the engineered strain (JX123) enhanced ethanol production from cellulosic hydrolysates as compared to other engineered haploid strains...
December 18, 2016: Bioresource Technology
https://www.readbyqxmd.com/read/28087399/advances-with-using-crispr-cas-mediated-gene-editing-to-treat-infections-with-hepatitis-b-virus-and-hepatitis-c-virus
#2
REVIEW
Buhle Moyo, Kristie Bloom, Tristan Scott, Abdullah Ely, Patrick Arbuthnot
Chronic infections with hepatitis B and hepatitis C viruses (HBV and HCV) account for the majority of cases of cirrhosis and hepatocellular carcinoma. Current therapies for the infections have limitations and improved efficacy is necessary to prevent complications in carriers of the viruses. In the case of HBV persistence, the replication intermediate comprising covalently closed circular DNA (cccDNA) is particularly problematic. Licensed therapies have little effect on cccDNA and HBV replication relapses following treatment withdrawal...
January 10, 2017: Virus Research
https://www.readbyqxmd.com/read/28081254/maternal-supply-of-cas9-to-zygotes-facilitates-the-efficient-generation-of-site-specific-mutant-mouse-models
#3
Alberto Cebrian-Serrano, Shijun Zha, Lars Hanssen, Daniel Biggs, Christopher Preece, Benjamin Davies
Genome manipulation in the mouse via microinjection of CRISPR/Cas9 site-specific nucleases has allowed the production time for genetically modified mouse models to be significantly reduced. Successful genome manipulation in the mouse has already been reported using Cas9 supplied by microinjection of a DNA construct, in vitro transcribed mRNA and recombinant protein. Recently the use of transgenic strains of mice overexpressing Cas9 has been shown to facilitate site-specific mutagenesis via maternal supply to zygotes and this route may provide an alternative to exogenous supply...
2017: PloS One
https://www.readbyqxmd.com/read/28081156/generation-of-a-stable-transgenic-swine-model-expressing-a-porcine-histone-2b-egfp-fusion-protein-for-cell-tracking-and-chromosome-dynamics-studies
#4
Renan B Sper, Sehwon Koh, Xia Zhang, Sean Simpson, Bruce Collins, Jeff Sommer, Robert M Petters, Ignacio Caballero, Jeff L Platt, Jorge A Piedrahita
Transgenic pigs have become an attractive research model in the field of translational research, regenerative medicine, and stem cell therapy due to their anatomic, genetic and physiological similarities with humans. The development of fluorescent proteins as molecular tags has allowed investigators to track cell migration and engraftment levels after transplantation. Here we describe the development of two transgenic pig models via SCNT expressing a fusion protein composed of eGFP and porcine Histone 2B (pH2B)...
2017: PloS One
https://www.readbyqxmd.com/read/28079885/mirna182-regulates-percentage-of-myeloid-and-erythroid-cells-in-chronic-myeloid-leukemia
#5
Deepak Arya, Sasikala P Sachithanandan, Cecil Ross, Dasaradhi Palakodeti, Shang Li, Sudhir Krishna
The deregulation of lineage control programs is often associated with the progression of haematological malignancies. The molecular regulators of lineage choices in the context of tyrosine kinase inhibitor (TKI) resistance remain poorly understood in chronic myeloid leukemia (CML). To find a potential molecular regulator contributing to lineage distribution and TKI resistance, we undertook an RNA-sequencing approach for identifying microRNAs (miRNAs). Following an unbiased screen, elevated miRNA182-5p levels were detected in Bcr-Abl-inhibited K562 cells (CML blast crisis cell line) and in a panel of CML patients...
January 12, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28077794/large-scale-genomic-deletions-mediated-by-crispr-cas9-system
#6
EDITORIAL
Yuning Song, Liangxue Lai, Zhanjun Li
No abstract text is available yet for this article.
January 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28077679/crispr-cas9-gene-repair-of-hematopoietic-stem-cells-from-patients-with-x-linked-chronic-granulomatous-disease
#7
Suk See De Ravin, Linhong Li, Xiaolin Wu, Uimook Choi, Cornell Allen, Sherry Koontz, Janet Lee, Narda Theobald-Whiting, Jessica Chu, Mary Garofalo, Colin Sweeney, Lela Kardava, Susan Moir, Angelia Viley, Pachai Natarajan, Ling Su, Douglas Kuhns, Kol A Zarember, Madhusudan V Peshwa, Harry L Malech
Gene repair of CD34(+) hematopoietic stem and progenitor cells (HSPCs) may avoid problems associated with gene therapy, such as vector-related mutagenesis and dysregulated transgene expression. We used CRISPR (clustered regularly interspaced short palindromic repeat)/Cas9 (CRISPR-associated 9) to repair a mutation in the CYBB gene of CD34(+) HSPCs from patients with the immunodeficiency disorder X-linked chronic granulomatous disease (X-CGD). Sequence-confirmed repair of >20% of HSPCs from X-CGD patients restored the function of NADPH (nicotinamide adenine dinucleotide phosphate) oxidase and superoxide radical production in myeloid cells differentiated from these progenitor cells in vitro...
January 11, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28077621/functional-redundancy-and-non-redundancy-between-two-troponin-c-isoforms-in-drosophila-adult-muscles
#8
Maria B Chechenova, Sara Maes, Sandy T Oas, Cloyce Nelson, Kaveh G Kiani, Anton L Bryantsev, Richard M Cripps
We investigated the functional overlap of two muscle Troponin C (TpnC) genes that are expressed in the adult fruit fly, Drosophila melanogaster: TpnC4 is predominantly expressed in the indirect flight muscles (IFM), whereas TpnC41C is the main isoform in the tergal depressor of the trochanter muscle (TDT or jump muscle). Using CRISPR/Cas9, we created a transgenic line with a homozygous deletion of TpnC41C, and compared its phenotype to a line lacking functional TpnC4 We found that the removal of either of these genes leads to expression of the other isoform in both muscle types...
January 11, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28077422/antxr2-knock-out-does-not-result-in-the-development-of-hypertension-in-rats
#9
Xiaoyan Liu, Wen Yuan, Jing Li, Lei Yang, Jun Cai
BACKGROUND: Our recent genetic study as well as robust evidences reported by previous genome-wide association studies (GWASs) have indicated that the single nucleotide polymorphism rs16998073, located near gene anthrax toxin receptor 2 (ANTXR2), was significantly associated with hypertension in Asians and Europeans. The aim of the present study was to determine whether ANTXR2 is the causal gene of hypertension at the 4q21 locus using an ANTXR2 knock-out model. METHODS: Relative expression of ANTXR2 in Wistar-Kyoto rats (WKYs) and spontaneously hypertensive rats (SHRs) were determined by real-time quantitative polymerase chain reaction and western blot analysis...
February 2017: American Journal of Hypertension
https://www.readbyqxmd.com/read/28077285/a-fluorophore-fusion-construct-of-human-profilin-i-with-non-compromized-poly-l-proline-binding-capacity-suitable-for-imaging
#10
Michaela Nejedla, Zhilun Li, Anna E Masser, Matteo Biancospino, Matthias Spiess, Sebastian D Mackowiak, Marc R Friedländer, Roger Karlsson
Profilin is vital for actin organization in eukaryotic cells. It controls actin filament formation by binding monomeric actin and numerous proteins involved in polarized actin assembly. Important for the latter is the interaction surface formed by the N- and C-terminal helices, which pack close to each other on one side of the molecule at distance from the actin site and mediate binding to poly-proline sequences present in many of the targeted proteins. Via these interactions profilin contributes to the spatiotemporal control of actin filament growth...
January 7, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28076467/the-search-for-novel-insecticide-targets-in-the-post-genomics-era-with-a-specific-focus-on-g-protein-coupled-receptors
#11
Michelle Ngai, Mary Ann McDowell
Insects are considered pests globally, implicated in the destruction of agricultural fields and transmission of pathogens that cause deadly human diseases, such as dengue, Zika and malaria. The diversity of the insecticide arsenal has remained stagnant for decades, but the recent rise of insecticide resistance fueled the discovery of novel modes of action, and the power of genomics has reinvigorated this search. This review discusses the importance of comparative and functional insect genomics in the identification of potential gene targets for an insecticidal mode of action with low off-target toxicity...
January 1, 2017: Memórias do Instituto Oswaldo Cruz
https://www.readbyqxmd.com/read/28074024/whole-genome-sequencing-of-invasion-resistant-cells-identifies-laminin-%C3%AE-2-as-a-host-factor-for-bacterial-invasion
#12
Xander M van Wijk, Simon Döhrmann, Björn M Hallström, Shangzhong Li, Bjørn G Voldborg, Brandon X Meng, Karen K McKee, Toin H van Kuppevelt, Peter D Yurchenco, Bernhard O Palsson, Nathan E Lewis, Victor Nizet, Jeffrey D Esko
: To understand the role of glycosaminoglycans in bacterial cellular invasion, xylosyltransferase-deficient mutants of Chinese hamster ovary (CHO) cells were created using clustered regularly interspaced short palindromic repeat (CRISPR) and CRISPR-associated gene 9 (CRISPR-cas9) gene targeting. When these mutants were compared to the pgsA745 cell line, a CHO xylosyltransferase mutant generated previously using chemical mutagenesis, an unexpected result was obtained. Bacterial invasion of pgsA745 cells by group B Streptococcus (GBS), group A Streptococcus, and Staphylococcus aureus was markedly reduced compared to the invasion of wild-type cells, but newly generated CRISPR-cas9 mutants were only resistant to GBS...
January 10, 2017: MBio
https://www.readbyqxmd.com/read/28073774/temporally-distinct-pd-l1-expression-by-tumor-and-host-cells-contributes-to-immune-escape
#13
Takuro Noguchi, Jeffrey P Ward, Matthew M Gubin, Cora D Arthur, Sang Hun Lee, Jasreet Hundal, Mark Selby, Robert F Graziano, Elaine R Mardis, Alan J Korman, Robert D Schreiber
Antibody blockade of Programmed Death-1 (PD-1) or its ligand, PD-L1, has led to unprecedented therapeutic responses in certain tumor-bearing individuals, but PD-L1 expression's prognostic value in stratifying cancer patients for such treatment remains unclear. Reports conflict on the significance of correlations between PD-L1 on tumor cells and positive clinical outcomes to PD-1/PD-L1 blockade. We investigated this issue using genomically-related, clonal subsets from the same methylcholanthrene-induced sarcoma: a highly immunogenic subset that is spontaneously eliminated in vivo by adaptive immunity and a less immunogenic subset that forms tumors in immunocompetent mice, but is sensitive to PD-1/PD-L1 blockade therapy...
January 10, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28071690/generation-of-germline-ablated-male-pigs-by-crispr-cas9-editing-of-the-nanos2-gene
#14
Ki-Eun Park, Amy V Kaucher, Anne Powell, Muhammad Salman Waqas, Shelley E S Sandmaier, Melissa J Oatley, Chi-Hun Park, Ahmed Tibary, David M Donovan, Le Ann Blomberg, Simon G Lillico, C Bruce A Whitelaw, Alan Mileham, Bhanu P Telugu, Jon M Oatley
Genome editing tools have revolutionized the generation of genetically modified animals including livestock. In particular, the domestic pig is a proven model of human physiology and an agriculturally important species. In this study, we utilized the CRISPR/Cas9 system to edit the NANOS2 gene in pig embryos to generate offspring with mono-allelic and bi-allelic mutations. We found that NANOS2 knockout pigs phenocopy knockout mice with male specific germline ablation but other aspects of testicular development are normal...
January 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28069043/fgf19-fgfr4-signaling-contributes-to-the-resistance-of-hepatocellular-carcinoma-to-sorafenib
#15
Lixia Gao, Xuli Wang, Yaoliang Tang, Shuang Huang, Chien-An Andy Hu, Yong Teng
BACKGROUND: Sorafenib, a multi-kinase inhibitor, is used as a standard therapy for advanced hepatocellular carcinoma (HCC). However, complete remission has not been achieved and the molecular basis of HCC resistance to sorafenib remains largely unknown. Previous studies have shown that fibroblast growth factor 19 (FGF19) expression correlates with tumor progression and poor prognosis of HCC. Here, we demonstrate the novel role of FGF19 in HCC resistance to sorafenib therapy. METHODS: FGF19 Knockdown cells were achieved by lentiviral-mediated interference, and FGFR4 knockout cells were achieved by CRISPR-Cas9...
January 9, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28068387/enhancing-targeted-genomic-dna-editing-in-chicken-cells-using-the-crispr-cas9-system
#16
Ling Wang, Likai Yang, Yijie Guo, Weili Du, Yajun Yin, Tao Zhang, Hongzhao Lu
The CRISPR/Cas9 system has enabled highly efficient genome targeted editing for various organisms. However, few studies have focused on CRISPR/Cas9 nuclease-mediated chicken genome editing compared with mammalian genomes. The current study combined CRISPR with yeast Rad52 (yRad52) to enhance targeted genomic DNA editing in chicken DF-1 cells. The efficiency of CRISPR/Cas9 nuclease-induced targeted mutations in the chicken genome was increased to 41.9% via the enrichment of the dual-reporter surrogate system...
2017: PloS One
https://www.readbyqxmd.com/read/28067909/smchd1-mutations-associated-with-a-rare-muscular-dystrophy-can-also-cause-isolated-arhinia-and-bosma-arhinia-microphthalmia-syndrome
#17
Natalie D Shaw, Harrison Brand, Zachary A Kupchinsky, Hemant Bengani, Lacey Plummer, Takako I Jones, Serkan Erdin, Kathleen A Williamson, Joe Rainger, Alexei Stortchevoi, Kaitlin Samocha, Benjamin B Currall, Donncha S Dunican, Ryan L Collins, Jason R Willer, Angela Lek, Monkol Lek, Malik Nassan, Shahrin Pereira, Tammy Kammin, Diane Lucente, Alexandra Silva, Catarina M Seabra, Colby Chiang, Yu An, Morad Ansari, Jacqueline K Rainger, Shelagh Joss, Jill Clayton Smith, Margaret F Lippincott, Sylvia S Singh, Nirav Patel, Jenny W Jing, Jennifer R Law, Nalton Ferraro, Alain Verloes, Anita Rauch, Katharina Steindl, Markus Zweier, Ianina Scheer, Daisuke Sato, Nobuhiko Okamoto, Christina Jacobsen, Jeanie Tryggestad, Steven Chernausek, Lisa A Schimmenti, Benjamin Brasseur, Claudia Cesaretti, Jose E García-Ortiz, Tatiana Pineda Buitrago, Orlando Perez Silva, Jodi D Hoffman, Wolfgang Mühlbauer, Klaus W Ruprecht, Bart L Loeys, Masato Shino, Angela M Kaindl, Chie-Hee Cho, Cynthia C Morton, Richard R Meehan, Veronica van Heyningen, Eric C Liao, Ravikumar Balasubramanian, Janet E Hall, Stephanie B Seminara, Daniel Macarthur, Steven A Moore, Koh-Ichiro Yoshiura, James F Gusella, Joseph A Marsh, John M Graham, Angela E Lin, Nicholas Katsanis, Peter L Jones, William F Crowley, Erica E Davis, David R FitzPatrick, Michael E Talkowski
Arhinia, or absence of the nose, is a rare malformation of unknown etiology that is often accompanied by ocular and reproductive defects. Sequencing of 40 people with arhinia revealed that 84% of probands harbor a missense mutation localized to a constrained region of SMCHD1 encompassing the ATPase domain. SMCHD1 mutations cause facioscapulohumeral muscular dystrophy type 2 (FSHD2) via a trans-acting loss-of-function epigenetic mechanism. We discovered shared mutations and comparable DNA hypomethylation patterning between these distinct disorders...
January 9, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28067901/targeting-samhd1-with-the-vpx-protein-to-improve-cytarabine-therapy-for-hematological-malignancies
#18
Nikolas Herold, Sean G Rudd, Linda Ljungblad, Kumar Sanjiv, Ida Hed Myrberg, Cynthia B J Paulin, Yaser Heshmati, Anna Hagenkort, Juliane Kutzner, Brent D G Page, José M Calderón-Montaño, Olga Loseva, Ann-Sofie Jemth, Lorenzo Bulli, Hanna Axelsson, Bianca Tesi, Nicholas C K Valerie, Andreas Höglund, Julia Bladh, Elisée Wiita, Mikael Sundin, Michael Uhlin, Georgios Rassidakis, Mats Heyman, Katja Pokrovskaja Tamm, Ulrika Warpman-Berglund, Julian Walfridsson, Sören Lehmann, Dan Grandér, Thomas Lundbäck, Per Kogner, Jan-Inge Henter, Thomas Helleday, Torsten Schaller
The cytostatic deoxycytidine analog cytarabine (ara-C) is the most active agent available against acute myelogenous leukemia (AML). Together with anthracyclines, ara-C forms the backbone of AML treatment for children and adults. In AML, both the cytotoxicity of ara-C in vitro and the clinical response to ara-C therapy are correlated with the ability of AML blasts to accumulate the active metabolite ara-C triphosphate (ara-CTP), which causes DNA damage through perturbation of DNA synthesis. Differences in expression levels of known transporters or metabolic enzymes relevant to ara-C only partially account for patient-specific differential ara-CTP accumulation in AML blasts and response to ara-C treatment...
January 9, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28067217/characterization-of-the-interplay-between-dna-repair-and-crispr-cas9-induced-dna-lesions-at-an-endogenous-locus
#19
Anne Bothmer, Tanushree Phadke, Luis A Barrera, Carrie M Margulies, Christina S Lee, Frank Buquicchio, Sean Moss, Hayat S Abdulkerim, William Selleck, Hariharan Jayaram, Vic E Myer, Cecilia Cotta-Ramusino
The CRISPR-Cas9 system provides a versatile toolkit for genome engineering that can introduce various DNA lesions at specific genomic locations. However, a better understanding of the nature of these lesions and the repair pathways engaged is critical to realizing the full potential of this technology. Here we characterize the different lesions arising from each Cas9 variant and the resulting repair pathway engagement. We demonstrate that the presence and polarity of the overhang structure is a critical determinant of double-strand break repair pathway choice...
January 9, 2017: Nature Communications
https://www.readbyqxmd.com/read/28066798/an-ngago-tool-for-genome-editing-did-crispr-cas9-just-find-a-competitor
#20
Qiang Wei, Junyi Liao, Xinyi Yu, Eric J Wang, Claire Wang, Hue H Luu, Rex C Haydon, Michael J Lee, Tong-Chuan He
While CRISPR/Cas9-mediated genome editing technology has been experiencing a rapid transformation during the past few years, a recent report on NgAgo-mediated single-stranded DNA-guided genome editing may offer an attractive alternative for genome manipulation. While it's too early to predict whether NgAgo will be able to compete with or be superior to CRISPR/Cas9, the scientific community is anxiously waiting for further optimization and broader applications of the NgAgo genome editing technology.
September 2016: Genes & Diseases
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