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Anti crispr

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https://www.readbyqxmd.com/read/29352444/activation-of-the-anti-aging-and-cognition-enhancing-gene-klotho-by-crispr-dcas9-transcriptional-effector-complex
#1
Ci-Di Chen, Ella Zeldich, Yuexuan Li, Andrea Yuste, Carmela R Abraham
Multiple lines of evidence show that the anti-aging and cognition-enhancing protein Klotho fosters neuronal survival, increases the anti-oxidative stress defense, and promotes remyelination of demyelinated axons. Thus, upregulation of the Klotho gene can potentially alleviate the symptoms and/or prevent the progression of age-associated neurodegenerative diseases such as Alzheimer's disease and demyelinating diseases such as multiple sclerosis. Here we used a CRISPR-dCas9 complex to investigate single-guide RNA (sgRNA) targeting the Klotho promoter region for efficient transcriptional activation of the Klotho gene...
January 19, 2018: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/29348170/crispr-rna-and-anti-crispr-protein-binding-to-the-xanthomonas-albilineans-csy1-csy2-heterodimer-in-the-type-i-f-crispr-cas-system
#2
Suji Hong, Donghyun Ka, Seo Jeong Yoon, Nayoung Suh, Migyeong Jeong, Jeong-Yong Suh, Euiyoung Bae
Clustered regularly interspaced short palindromic repeats (CRISPRs) and CRISPR-associated (Cas) proteins provide microbial adaptive immunity against bacteriophages. In type I-F CRISPR-Cas systems, multiple Cas proteins (Csy1-4) comprise a surveillance complex (Csy complex) with CRISPR RNA (crRNA) for target recognition. Here, we report the biochemical characterization of the Csy1-Csy2 subcomplex from Xanthomonas albilineans, including the analysis of its interaction with crRNA and also AcrF2, an anti-CRISPR (Acr) protein from a phage that infects Pseudomonas aeruginosa The X...
January 18, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29335437/deubiquitinase-usp13-dictates-mcl1-stability-and-sensitivity-to-bh3-mimetic-inhibitors
#3
Shengzhe Zhang, Meiying Zhang, Ying Jing, Xia Yin, Pengfei Ma, Zhenfeng Zhang, Xiaojie Wang, Wen Di, Guanglei Zhuang
MCL1 is a pivot member of the anti-apoptotic BCL-2 family proteins. While a distinctive feature of MCL1 resides in its efficient ubiquitination and destruction, the deubiquitinase USP9X has been implicated in the preservation of MCL1 expression by removing the polyubiquitin chains. Here we perform an unbiased siRNA screen and identify that the second deubiquitinase, USP13, regulates MCL1 stability in lung and ovarian cancer cells. Mechanistically, USP13 interacts with and stabilizes MCL1 via deubiquitination...
January 15, 2018: Nature Communications
https://www.readbyqxmd.com/read/29311364/isg15-induced-il-10-is-a-novel-anti-inflammatory-myeloid-axis-disrupted-during-active-tuberculosis
#4
Paula Fernandes Dos Santos, Johan Van Weyenbergh, Murilo Delgobo, Daniel de Oliveira Patricio, Brian J Ferguson, Rodrigo Guabiraba, Tim Dierckx, Soraya Maria Menezes, André Báfica, Daniel Santos Mansur
IFN-stimulated gene 15 (ISG15) deficiency in humans leads to severe IFNopathies and mycobacterial disease, the latter being previously attributed to its extracellular cytokine-like activity. In this study, we demonstrate a novel role for secreted ISG15 as an IL-10 inducer, unique to primary human monocytes. A balanced ISG15-induced monocyte/IL-10 versus lymphoid/IFN-γ expression, correlating with p38 MAPK and PI3K signaling, was found using targeted in vitro and ex vivo systems analysis of human transcriptomic datasets...
January 8, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29304331/rapid-and-scalable-characterization-of-crispr-technologies-using-an-e-%C3%A2-coli-cell-free-transcription-translation-system
#5
Ryan Marshall, Colin S Maxwell, Scott P Collins, Thomas Jacobsen, Michelle L Luo, Matthew B Begemann, Benjamin N Gray, Emma January, Anna Singer, Yonghua He, Chase L Beisel, Vincent Noireaux
CRISPR-Cas systems offer versatile technologies for genome engineering, yet their implementation has been outpaced by ongoing discoveries of new Cas nucleases and anti-CRISPR proteins. Here, we present the use of E. coli cell-free transcription-translation (TXTL) systems to vastly improve the speed and scalability of CRISPR characterization and validation. TXTL can express active CRISPR machinery from added plasmids and linear DNA, and TXTL can output quantitative dynamics of DNA cleavage and gene repression-all without protein purification or live cells...
January 4, 2018: Molecular Cell
https://www.readbyqxmd.com/read/29301958/a-major-chromatin-regulator-determines-resistance-of-tumor-cells-to-t-cell-mediated-killing
#6
Deng Pan, Aya Kobayashi, Peng Jiang, Lucas Ferrari de Andrade, Rong En Tay, Adrienne Luoma, Daphne Tsoucas, Xintao Qiu, Klothilda Lim, Prakash Rao, Henry W Long, Guo-Cheng Yuan, John Doench, Myles Brown, Shirley Liu, Kai W Wucherpfennig
Many human cancers are resistant to immunotherapy for reasons that are poorly understood. We used a genome-scale CRISPR/Cas9 screen to identify mechanisms of tumor cell resistance to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. Inactivation of >100 genes sensitized mouse B16F10 melanoma cells to killing by T cells, including Pbrm1, Arid2 and Brd7, which encode components of the PBAF form of the SWI/SNF chromatin remodeling complex. Loss of PBAF function increased tumor cell sensitivity to interferon-γ, resulting in enhanced secretion of chemokines that recruit effector T cells...
January 4, 2018: Science
https://www.readbyqxmd.com/read/29299169/jujube-leaf-green-tea-extracts-inhibits-hepatocellular-carcinoma-cells-by-activating-ampk
#7
H X Liu, M Q Xu, S P Li, S Tian, M X Guo, J Y Qi, C J He, X S Zhao
Here we evaluated the anti-hepatocellular carcinoma activity by the Jujube leaf green tea extracts (JLGTE). We showed that JLGTE exerted anti-proliferative, cytotoxic and pro-apoptotic activities against HepG2 and primary human hepatocellular carcinoma cells. It was however non-cytotoxic to the normal hepatocytes. JLGTE activated AMP-activated protein kinase (AMPK) signaling, which was required for its cytotoxicity against hepatocellular carcinoma cells. Silence of AMPKα1, via targeted short hairpin RNAs or CRISPR-Cas9 genome editing, inhibited JLGTE-induced AMPK activation and HepG2 cell apoptosis...
December 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/29282220/inflammasome-adaptor-asc-suppresses-apoptosis-of-gastric-cancer-cells-by-an-il-18-mediated-inflammation-independent-mechanism
#8
Brendan J Jenkins, Virginie Deswaerte, Paul M Nguyen, Alison West, Alison F Browning, Liang Yu, Saleela Ruwanpura, Jesse Balic, Thaleia Livis, Charlotte Girard, Adele Preaudet, Hiroko Oshima, Ka Yee Fung, Hazel Tye, Meri Najdovska, Matthias Ernst, Masanobu Oshima, Cem Gabay, Tracy L Putoczki
Inflammasomes are key regulators of innate immunity in chronic inflammatory disorders and autoimmune diseases, but their role in inflammation-associated tumorigenesis remains ill-defined. Here we reveal a pro-tumorigenic role in gastric cancer (GC) for the key inflammasome adaptor ASC and its effector cytokine IL-18. Genetic ablation of ASC in the gp130F/F spontaneous mouse model of intestinal-type GC suppressed tumorigenesis by augmenting caspase-8-like apoptosis in the gastric epithelium, independently from effects on myeloid cells and mucosal inflammation...
December 27, 2017: Cancer Research
https://www.readbyqxmd.com/read/29251498/protein-inhibitors-of-crispr-cas9
#9
Joseph Bondy-Denomy
Bacteria are under constant predation from viruses, called bacteriophages (phages). This threat has driven the evolution of multiple defense systems, including the CRISPR-Cas immune pathway. Phages are not passive bystanders in their CRISPR-mediated demise however, as many have developed potent inhibitors of the bacterial adaptive immune system. While many CRISPR-Cas systems have been identified in nature, along with cognate "anti-CRISPR" proteins, the Type II CRISPR-Cas9 system has received much of the focus, after being co-opted as a revolutionary genome editing tool...
December 18, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/29245982/endothelial-derived-interleukin-6-induces-cancer-stem-cell-motility-by-generating-a-chemotactic-gradient-towards-blood-vessels
#10
Hong Sun Kim, Yu-Chih Chen, Felipe Nör, Kristy A Warner, April Andrews, Vivian P Wagner, Zhaocheng Zhang, Zhixiong Zhang, Manoela D Martins, Alexander T Pearson, Euisik Yoon, Jacques E Nör
Recent evidence suggests that the metastatic spread of head and neck squamous cell carcinomas (HNSCC) requires the function of cancer stem cells endowed with multipotency, self-renewal, and high tumorigenic potential. We demonstrated that cancer stem cells reside in perivascular niches and are characterized by high aldehyde dehydrogenase (ALDH) activity and high CD44 expression (ALDHhighCD44high) in HNSCC. Here, we hypothesize that endothelial cell-secreted interleukin-6 (IL-6) contributes to tumor progression by enhancing the migratory phenotype and survival of cancer stem cells...
November 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/29236701/anti-leukemic-activity-of-bortezomib-and-carfilzomib-on-b-cell-precursor-all-cell-lines
#11
Kazuya Takahashi, Takeshi Inukai, Toshihiko Imamura, Mio Yano, Chihiro Tomoyasu, David M Lucas, Atsushi Nemoto, Hiroki Sato, Meixian Huang, Masako Abe, Keiko Kagami, Tamao Shinohara, Atsushi Watanabe, Shinpei Somazu, Hiroko Oshiro, Koshi Akahane, Kumiko Goi, Jiro Kikuchi, Yusuke Furukawa, Hiroaki Goto, Masayoshi Minegishi, Shotaro Iwamoto, Kanji Sugita
Prognosis of childhood acute lymphoblastic leukemia (ALL) has been dramatically improved. However, prognosis of the cases refractory to primary therapy is still poor. Recent phase 2 study on the efficacy of combination chemotherapy with bortezomib (BTZ), a proteasome inhibitor, for refractory childhood ALL demonstrated favorable clinical outcomes. However, septic death was observed in over 10% of patients, indicating the necessity of biomarkers that could predict BTZ sensitivity. We investigated in vitro BTZ sensitivity in a large panel of ALL cell lines that acted as a model system for refractory ALL, and found that Philadelphia chromosome-positive (Ph+) ALL, IKZF1 deletion, and biallelic loss of CDKN2A were associated with favorable response...
2017: PloS One
https://www.readbyqxmd.com/read/29233979/extracellular-vesicles-from-human-induced-pluripotent-stem-cell-derived-mesenchymal-stromal-cells-hipsc-mscs-protect-against-renal-ischemia-reperfusion-injury-via-delivering-specificity-protein-sp1-and-transcriptional-activating-of-sphingosine-kinase-1-and
#12
Xiaodong Yuan, Dawei Li, Xiaosong Chen, Conghui Han, Longmei Xu, Tao Huang, Zhen Dong, Ming Zhang
Renal ischemia-reperfusion is a main cause of acute kidney injury (AKI), which is associated with high mortality. Here we show that extracellular vesicles (EVs) secreted from hiPSC-MSCs play a critical role in protection against renal I/R injury. hiPSC-MSCs-EVs can fuse with renal cells and deliver SP1 into target cells, subsequently active SK1 expression and increase S1P formation. Chromatin immunoprecipitation (ChIP) analyses and luciferase assay were used to confirm SP1 binds directly to the SK1 promoter region and promote promoter activity...
December 11, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29233895/disabling-a-type-i-e-crispr-cas-nuclease-with-a-bacteriophage-encoded-anti-crispr-protein
#13
April Pawluk, Megha Shah, Marios Mejdani, Charles Calmettes, Trevor F Moraes, Alan R Davidson, Karen L Maxwell
CRISPR (clustered regularly interspaced short palindromic repeat)-Cas adaptive immune systems are prevalent defense mechanisms in bacteria and archaea. They provide sequence-specific detection and neutralization of foreign nucleic acids such as bacteriophages and plasmids. One mechanism by which phages and other mobile genetic elements are able to overcome the CRISPR-Cas system is through the expression of anti-CRISPR proteins. Over 20 different families of anti-CRISPR proteins have been described, each of which inhibits a particular type of CRISPR-Cas system...
December 12, 2017: MBio
https://www.readbyqxmd.com/read/29228209/cd38-knockout-suppresses-tumorigenesis-in-mice-and-clonogenic-growth-of-human-lung-cancer-cells
#14
Xiangning Bu, Jiro Kato, Julie A Hong, Maria J Merino, David S Schrump, Frances E Lund, Joel Moss
The ectodomain of the plasma membrane ecto-enzyme CD38 functions as both an NAD glycohydrolase and an ADP-ribosyl cyclase by catalyzing, respectively, the conversion of NAD to nicotinamide and ADP-ribose or cyclic ADP-ribose. CD38 is attracting particular attention in cancer therapy. An anti-CD38 monoclonal antibody (daratumumab) was approved for treatment of patients with multiple myeloma. However, the role of CD38 in non-hematological malignancies has not been explored. Previously, we reported that ADP-ribose-acceptor hydrolase (ARH)-1 deficiency in mice was associated with tumor development...
December 8, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/29222162/dual-inhibition-of-pik3c3-and-fgfr-as-a-new-therapeutic-approach-to-treat-bladder-cancer
#15
Chun-Han Chen, C Changou, Tsung-Han Hsieh, Yu-Ching Lee, Cheng-Ying Chu, Kai-Cheng Hsu, Hao-Ching Wang, Yu-Chen Lin, Yan-Ni Lo, Yun-Ru Liu, Jing-Ping Liou, Yun Yen
PURPOSE: MPT0L145 has been developed as a FGFR inhibitor exhibiting significant anti-bladder cancer activity in vitro and in vivo via promoting autophagy-dependent cell death. Here, we aim to elucidate the underlying mechanisms. EXPERIMENTAL DESIGN: Autophagy flux, morphology and intracellular organelles were evaluated by western blotting, transmission electron microscope and fluorescence microscope. Molecular docking, surface plasmon resonance assay were performed to identify drug-protein interaction...
December 8, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29221169/targeting-pp2a-activates-ampk-signaling-to-inhibit-colorectal-cancer-cells
#16
Cuiping Dai, Xuning Zhang, Da Xie, Peipei Tang, Chunmei Li, Yi Zuo, Baofei Jiang, Caiping Xue
LB-100 is a novel PP2A inhibitor. Its activity in human colorectal cancer (CRC) cells was tested. The in vitro studies demonstrated that LB-100 inhibited survival and proliferation of both established CRC cells (HCT-116 and HT-29 lines) and primary human colon cancer cells. Further, LB-100 activated apoptosis and induced G1-S cell cycle arrest in CRC cells. LB-100 inhibited PP2A activity and activated AMPK signaling in CRC cells. AMPKα1 dominant negative mutation, shRNA-mediated knockdown or complete knockout (by CRISPR/Cas9 method) largely attenuated LB-100-induced AMPK activation and HCT-116 cytotoxicity...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29215459/complete-b-cell-deficiency-reduces-allograft-inflammation-and-intragraft-macrophages-a-rat-kidney-transplant-model
#17
Sarah E Panzer, Nancy A Wilson, Bret M Verhoven, Ding Xiang, C Dustin Rubinstein, Robert R Redfield, Weixiong Zhong, Shannon R Reese
BACKGROUND: Increasingly it is being appreciated that B cells have broad roles beyond the humoral response, and are able to contribute to and regulate inflammation. The specific role of B cells in the pathogenesis of early allograft inflammation remains unclear. METHODS: To address this question, we generated B cell deficient Lewis rats via CRISPR technology. In a full mismatch transplant model, kidneys from Brown Norway donors were transplanted into B cell deficient Lewis recipients (B) or wild type Lewis recipients...
December 5, 2017: Transplantation
https://www.readbyqxmd.com/read/29203900/intracellular-immunization-against-hiv-infection-with-an-intracellular-antibody-that-mimics-hiv-integrase-binding-to-the-cellular-ledgf-protein
#18
Leyuan Bao, Clare Hannon, Abimael Cruz-Mignoni, Denis Ptchelkine, Mei-Yi Sun, Ami Miller, Wilawan Bunjobpol, Camilo E Quevedo, Mariliza Derveni, Jennifer Chambers, Alison Simmons, Simon E V Phillips, Terence H Rabbitts
Preventing the protein-protein interaction of the cellular chromatin binding protein Lens Epithelium-Derived Growth Factor (LEDGF) and human immunodeficiency virus (HIV) integrase is an important possible strategy for anti-viral treatment for AIDS. We have used Intracellular Antibody Capture technology to isolate a single VH antibody domain that binds to LEDGF. The crystal structure of the LEDGF-VH complex reveals that the single domain antibody mimics the effect of binding of HIV integrase to LEDGF which is crucial for HIV propagation...
December 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29184000/a-subclass-of-serum-anti-znt8-antibodies-directed-to-the-surface-of-live-pancreatic-beta-cells
#19
Chengfeng Merriman, Qiong Huang, Wei Gu, Liping Yu, Dax Fu
The islet-specific zinc transporter ZnT8 is a major self-antigen found in insulin granules of pancreatic beta-cells. Frequent insulin secretion exposes ZnT8 to the cell surface, but the humoral antigenicity of the surface-displayed ZnT8 remains unknown. Here we show that a membrane-embedded human ZnT8 antigen trigged a vigorous immune response in ZnT8-knockout mice. About 50% of serum immunoreactivities toward ZnT8 were mapped to its transmembrane domain that is accessible to extracellular ZnT8 antibody (ZnT8A)...
November 28, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29182776/crystal-structure-of-an-anti-crispr-protein-acriia1
#20
Donghyun Ka, So Young An, Jeong-Yong Suh, Euiyoung Bae
Clustered regularly interspaced short palindromic repeats (CRISPRs) and CRISPR-associated (Cas) proteins provide bacteria with RNA-based adaptive immunity against phage infection. To counteract this defense mechanism, phages evolved anti-CRISPR (Acr) proteins that inactivate the CRISPR-Cas systems. AcrIIA1, encoded by Listeria monocytogenes prophages, is the most prevalent among the Acr proteins targeting type II-A CRISPR-Cas systems and has been used as a marker to identify other Acr proteins. Here, we report the crystal structure of AcrIIA1 and its RNA-binding affinity...
November 22, 2017: Nucleic Acids Research
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