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Transcription activator-like effectors

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https://www.readbyqxmd.com/read/28810059/targeted-genome-editing-in-caenorhabditis-elegans-using-crispr-cas9
#1
REVIEW
Behnom Farboud
Utilization of programmable nucleases to generate DNA lesions at precise endogenous sequences has transformed the ability to edit genomes from microbes to plants and animals. This is especially true in organisms that previously lacked the means to engineer precise genomic changes, like Caenorhabditis elegans. C. elegans is a 1 mm long free-living, nonparasitic, nematode worm, which is easily cultivated in a laboratory. Its detailed genetic map and relatively compact genome (~100 megabases) helped make it the first metazoan to have its entire genome sequenced...
August 15, 2017: Wiley Interdisciplinary Reviews. Developmental Biology
https://www.readbyqxmd.com/read/28807724/the-versatile-functions-of-lrr-only-proteins-in-mollusk-chlamys-farreri
#2
Mengqiang Wang, Lingling Wang, Zhihao Jia, Xiudan Wang, Qilin Yi, Zhao Lv, Linsheng Song
Leucine-rich repeat (LRR)-only proteins are involved in the innate immune responses as they mediate protein-ligand interactions. In the present study, three novel LRR-only proteins, CfLRRop-4, CfLRRop-5 and CfLRRop-6, were identified and characterized from Zhikong scallop Chlamys farreri. They all contained LRR motifs with consensus signature sequences of LxxLxLxxNxL or LxxLxLxxCxxL. All the mRNA transcripts of three CfLRRops were high abundant in hepatopancreas, gills and gonads, and their mRNA transcripts in hemocytes could respond to the stimulations of different microbes, including Vibrio anguillarum, Micrococcus luteus and Pichia pastoris...
August 11, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/28805663/yap-taz-regulates-sprouting-angiogenesis-and-vascular-barrier-maturation
#3
Jongshin Kim, Yoo Hyung Kim, Jaeryung Kim, Do Young Park, Hosung Bae, Da-Hye Lee, Kyun Hoo Kim, Seon Pyo Hong, Seung Pil Jang, Yoshiaki Kubota, Young-Guen Kwon, Dae-Sik Lim, Gou Young Koh
Angiogenesis is a multistep process that requires coordinated migration, proliferation, and junction formation of vascular endothelial cells (ECs) to form new vessel branches in response to growth stimuli. Major intracellular signaling pathways that regulate angiogenesis have been well elucidated, but key transcriptional regulators that mediate these signaling pathways and control EC behaviors are only beginning to be understood. Here, we show that YAP/TAZ, a transcriptional coactivator that acts as an end effector of Hippo signaling, is critical for sprouting angiogenesis and vascular barrier formation and maturation...
August 14, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28801292/-oxidized-low-density-lipoprotein-modulates-differentiation-of-murine-memory-cd8-t-cell-subpopulations
#4
Hua Zheng, Ze-Hang Lin, Yan-Mei Zhang, Chen-Fei Zhou, Xuan Liu, Sha Wu
OBJECTIVE: To investigate effect of oxidized low-density lipoprotein (ox-LDL) on memory CD8(+) T cell subpopulation differentiation in mice with autoimmune diabetes. METHODS: Cultured splenic CD8(+) T cells from pre-diabetic NOD mice isolated with magnetic beads were treated with 30 µg/mL ox-LDL and 10 U/mL interleukin-2 (IL-2) for 24 h and the control cells were treated with IL-2 only. Flow cytometry was used to determine the percentage of splenic CD8(+)IFN-γ(+) T cells, expressions of CD8, CD44 and CD62L on the T cells, and the activation of T cell factor-1 (TCF-1) and STAT-3...
August 20, 2017: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
https://www.readbyqxmd.com/read/28797638/a-novel-tnfaip8-gene-mediates-l-arginine-metabolism-in-apostichopus-japonicus
#5
Yina Shao, Huahui Chen, Miao Lv, Chenghua Li, Weiwei Zhang, Ye Li, Xuelin Zhao, Yongbo Bao
Tumor necrosis factor (TNF)-α-induced protein 8 (TNFAIP8) family is a newly identified protein with vital roles in maintaining immune homeostasis. In the current study, we first cloned and characterized a TNFAIP8 gene from the invertebrate sea cucumber Apostichopus japonicus. The gene was designated as AjTNFAIP8. The full-length cDNA of AjTNFAIP8 was 1455 bp long and encoded a matured protein of 201 amino acid residues. Structural analysis indicated that AjTNFAIP8 had a death effector domain (DED)-like domain and composed of six α-helices...
August 7, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28795454/the-tcf7l2-pgc1%C3%AE-axis-connects-mitochondrial-biogenesis-and-metabolic-shift-with-stem-cell-commitment-to-hepatic-differentiation
#6
Anaïs Wanet, Marino Caruso, Jean-Baka Domelevo Entfellner, Mehdi Najar, Antoine Fattaccioli, Catherine Demazy, Jonathan Evraerts, Hoda El-Kehdy, Guillaume Pourcher, Etienne Sokal, Thierry Arnould, Nicki Tiffin, Mustapha Najimi, Patricia Renard
Increasing evidence supports that modifications in the mitochondrial content, oxidative phosphorylation (OXPHOS) activity, and cell metabolism influence the fate of stem cells. However, the regulators involved in the crosstalk between mitochondria and stem cell fate remain poorly characterized. Here, we identified a transcriptional regulatory axis, composed of TCF7L2 (transcription factor 7 like 2, a downstream effector of the Wnt/β-catenin pathway, repressed during differentiation) and PGC-1α (peroxisome proliferator-activated receptor gamma coactivator 1 alpha, the master regulator of mitochondrial biogenesis, induced during differentiation), coupling the loss of pluripotency and early commitment to differentiation, to the initiation of mitochondrial biogenesis and metabolic shift toward OXPHOS...
August 10, 2017: Stem Cells
https://www.readbyqxmd.com/read/28794449/il-7r%C3%AE-glutamylation-and-activation-of-transcription-factor-sall3-promote-group-3-ilc-development
#7
Benyu Liu, Buqing Ye, Xiaoxiao Zhu, Guanling Huang, Liuliu Yang, Pingping Zhu, Ying Du, Jiayi Wu, Shu Meng, Yong Tian, Zusen Fan
Group 3 innate lymphoid cells (ILC3) promote lymphoid organogenesis and potentiate immune responses against bacterial infection. However, how ILC3 cells are developed and maintained is still unclear. Here, we show that carboxypeptidase CCP2 is highly expressed in common helper-like innate lymphoid progenitors, the progenitor of innate lymphoid cells, and CCP2 deficiency increases ILC3 numbers. Interleukin-7 receptor subunit alpha (IL-7Rα) is identified as a substrate of CCP2 for deglutamylation, and IL-7Rα polyglutamylation is catalyzed by polyglutamylases TTLL4 and TTLL13 in common helper-like innate lymphoid progenitors...
August 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/28782493/big-data-and-genome-editing-technology-a-new-paradigm-of-cardiovascular-genomics
#8
Chayakrit Krittanawong, Tao Sun, Eyal Herzog
Cardiovascular diseases (CVDs) encompasse a range of conditions extending from congenital heart disease to acute coronary syndrome most of which are heterogenous in nature and some of them are multiple genetic loci. However, the pathogenesis of most CVDs remains incompletely understood. The advance in genome-editing technologies, an engineering process of DNA sequences at precise genomic locations, has enabled a new paradigm that human genome can be precisely modified to achieve a therapeutic effect. Genome-editing includes the correction of genetic variants that cause disease, the addition of therapeutic genes to specific sites in the genomic locations, and the removal of deleterious genes or genome sequences...
August 4, 2017: Current Cardiology Reviews
https://www.readbyqxmd.com/read/28777806/claudin-4-knockout-by-talen-mediated-gene-targeting-in-mdck-cells-claudin-4-is-dispensable-for-the-permeability-properties-of-tight-junctions-in-wild-type-mdck-cells
#9
Shinsaku Tokuda, Toyohiro Hirai, Mikio Furuse
Epithelia act as a barrier between the internal and external environments, and the movement of substances via the paracellular pathway is regulated by tight junctions (TJs). Claudins are major determinants of TJ permeability. Claudin-4 was the first claudin whose involvement in the TJ permeability in cultured cells was directly demonstrated, but the permeability properties of individual claudins including claudin-4 are still incompletely clarified. In this study, we established claudin-4 knockout cells using transcription activator-like effector nucleases (TALENs), a recently developed method for genome editing, and investigated the permeability property of claudin-4 in MDCK II cells...
2017: PloS One
https://www.readbyqxmd.com/read/28775123/tlr9-stimulation-can-induce-ikappabzeta-expression-and-igm-secretion-in-chronic-lymphocytic-leukemia-cells
#10
Eleonora Fonte, Maria Giovanna Vilia, Daniele Reverberi, Ilenia Sana, Lydia Scarfò, Pamela Ranghetti, Ugo Orfanelli, Simone Cenci, Giovanna Cutrona, Paolo Ghia, Marta Muzio
Chronic lymphocytic leukemia cells strongly depend on external stimuli for their survival. Both antigen receptor and co-stimulatory receptors including Toll-Like Receptors can modulate viability and proliferation of leukemic cells. Toll-Like Receptors ligands, and particularly the TLR9 ligand CpG, mediate heterogeneous responses in patient samples reflecting their clinical course. However, the molecular framework of the key signaling events underlying such heterogeneity is undefined. We focused our studies on a subset of chronic lymphocytic leukemia cases characterized by expression of CD38 and unmutated immunoglobulin genes, that respond to CpG with enhanced metabolic cell activity...
August 3, 2017: Haematologica
https://www.readbyqxmd.com/read/28775072/lmo2-lim-domain-only-2-modulates-sphk1-sphingosine-kinase-and-promotes-endothelial-cell-migration
#11
Gianfranco Matrone, Shu Meng, Qilin Gu, Jie Lv, Longhou Fang, Kaifu Chen, John P Cooke
OBJECTIVE: Lmo (LIM-domain-only)2 transcription factor is involved in hematopoiesis and vascular remodeling. Sphk (sphingosine kinase)1 phosphorylates sphingosine to S1P (sphingosine-1-phosphate). We hypothesized that Lmo2 regulates Sphk1 to promote endothelial cell (EC) migration and vascular development. APPROACH AND RESULTS: Lmo2 and Sphk1 knockdown (KD) were performed in Tg(fli1:EGFP) (y1) zebra fish and in human umbilical vein EC. Rescue of phenotypes or overexpression of these factors were achieved using mRNA encoding Lmo2 or Sphk1...
August 3, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28770027/the-genome-of-the-cotton-bacterial-blight-pathogen-xanthomonas-citri-pv-malvacearum-strain-msct1
#12
Kurt C Showmaker, Mark A Arick, Chuan-Yu Hsu, Brigitte E Martin, Xiaoqiang Wang, Jiayuan Jia, Martin J Wubben, Robert L Nichols, Tom W Allen, Daniel G Peterson, Shi-En Lu
Xanthomonas citri pv. malvacearum is a major pathogen of cotton, Gossypium hirsutum L.. In this study we report the complete genome of the X. citri pv. malvacearum strain MSCT1 assembled from long read DNA sequencing technology. The MSCT1 genome is the first X. citri pv. malvacearum genome with complete coding regions for X. citri pv. malvacearum transcriptional activator-like effectors. In addition functional and structural annotations are presented in this study that will provide a foundation for future pathogenesis studies with MSCT1...
2017: Standards in Genomic Sciences
https://www.readbyqxmd.com/read/28767147/programmed-death-1-is-highly-expressed-on-cd8-cd57-t-cells-in-patients-with-stable-multiple-sclerosis-and-inhibits-their-cytotoxic-response-to-ebv
#13
Maria T Cencioni, Roberta Magliozzi, Richard Nicholas, Rehiana Ali, Omar Malik, Richard Reynolds, Giovanna Borsellino, Luca Battistini, Paolo Muraro
Growing evidence points to a deregulated response to Epstein-Barr virus (EBV) in the CNS of patients with Multiple Sclerosis (pwMS) as a possible cause of disease. In this study, we have investigated the response of a subpopulation of effector CD8+ T cells to EBV in 36 healthy donors and in 35 pwMS in active and inactive disease. We have measured the expression of markers of degranulation, the release of cytokines, cytotoxicity and the regulation of effector functions by inhibitory receptors, such as programmed death-1 (PD-1) and human inhibitor receptor Ig-like transcript 2 (ILT2)...
August 2, 2017: Immunology
https://www.readbyqxmd.com/read/28765224/genome-wide-sensitivity-analysis-of-the-microsymbiont-sinorhizobium-meliloti-to-symbiotically-important-defensin-like-host-peptides
#14
Markus F F Arnold, Mohammed Shabab, Jon Penterman, Kevin L Boehme, Joel S Griffitts, Graham C Walker
The model legume species Medicago truncatula expresses more than 700 nodule-specific cysteine-rich (NCR) signaling peptides that mediate the differentiation of Sinorhizobium meliloti bacteria into nitrogen-fixing bacteroids. NCR peptides are essential for a successful symbiosis in legume plants of the inverted-repeat-lacking clade (IRLC) and show similarity to mammalian defensins. In addition to signaling functions, many NCR peptides exhibit antimicrobial activity in vitro and in vivo Bacterial resistance to these antimicrobial activities is likely to be important for symbiosis...
August 1, 2017: MBio
https://www.readbyqxmd.com/read/28753655/bacterial-effector-nlel-promotes-enterohemorrhagic-e-coli-induced-attaching-and-effacing-lesions-by-ubiquitylating-and-inactivating-jnk
#15
Xiangpeng Sheng, Qing You, Hongnian Zhu, ZeNan Chang, Qingrun Li, Haifeng Wang, Chen Wang, Hongyan Wang, Lijian Hui, Chongtao Du, Xiaoduo Xie, Rong Zeng, Anning Lin, Dongfang Shi, Kangcheng Ruan, Jinghua Yan, George Fu Gao, Feng Shao, Ronggui Hu
As a major diarrheagenic human pathogen, enterohemorrhagic Escherichia coli (EHEC) produce attaching and effacing (A/E) lesions, characterized by the formation of actin pedestals, on mammalian cells. A bacterial T3SS effector NleL from EHEC O157:H7 was recently shown to be a HECT-like E3 ligase in vitro, but its biological functions and host targets remain elusive. Here, we report that NleL is required to effectively promote EHEC-induced A/E lesions and bacterial infection. Furthermore, human c-Jun NH2-terminal kinases (JNKs) were identified as primary substrates of NleL...
July 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28747383/ischemia-reperfusion-induces-interferon-stimulated-gene-expression-in-microglia
#16
Ashley McDonough, Richard V Lee, Shahani Noor, Chungeun Lee, Thu Le, Michael Iorga, Jessica L H Phillips, Sean Murphy, Thomas Möller, Jonathan R Weinstein
Innate immune signaling is important in the pathophysiology of ischemia/reperfusion (stroke) induced injury and recovery. Several lines of evidence support a central role for microglia in these processes. Recent work has identified Toll-like receptors (TLRs) and type I interferon (IFN) signaling in both ischemia/reperfusion-induced brain injury and ischemic preconditioning-mediated neuroprotection. To determine the effects of 'ischemia/reperfusion-like' conditions on microglia we carried out genomic analyses on wild-type (WT) and TLR4(-/-) cultured microglia following sequential exposure to hypoxia/hypoglycemia and normoxia/normoglycemia (H/H-N/N)...
July 26, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28745269/hepatitis-b-virus-prevents-excessive-viral-production-via-reduction-of-cell-death-inducing-dff45-like-effectors
#17
Jun Yasumoto, Hirotake Kasai, Kentaro Yoshimura, Teruhime Otoguro, Koichi Watashi, Takaji Wakita, Atsuya Yamashita, Tomohisa Tanaka, Sen Takeda, Kohji Moriishi
The relationship between hepatitis B virus (HBV) infection and lipid accumulation remains largely unknown. In this study, we investigated the effect of HBV propagation on lipid droplet growth in HBV-infected cells and HBV-producing cell lines, HepG2.2.15 and HBV-inducible Hep38.7-Tet. The amount of intracellular triglycerides was significantly reduced in HBV-infected and HBV-producing cells compared with HBV-lacking control cells. Electron and immunofluorescent microscopic analyses showed that the average size of a single lipid droplet (LD) was significantly less in the HBV-infected and HBV-producing cells than in the HBV-lacking control cells...
July 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28732771/application-of-the-gene-editing-tool-crispr-cas9-for-treating-neurodegenerative-diseases
#18
REVIEW
Nivya Kolli, Ming Lu, Panchanan Maiti, Julien Rossignol, Gary Leo Dunbar
Increased accumulation of transcribed protein from the damaged DNA and reduced DNA repair capability contributes to numerous neurological diseases for which effective treatments are lacking. Gene editing techniques provide new hope for replacing defective genes and DNA associated with neurological diseases. With advancements in using such editing tools as zinc finger nucleases (ZFNs), meganucleases, and transcription activator-like effector nucleases (TALENs), etc., scientists are able to design DNA-binding proteins, which can make precise double-strand breaks (DSBs) at the target DNA...
July 18, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28729031/knockout-of-the-urate-oxidase-gene-provides-a-stable-mouse-model-of-hyperuricemia-associated-with-metabolic-disorders
#19
Jie Lu, Xu Hou, Xuan Yuan, Lingling Cui, Zhen Liu, Xinde Li, Lidan Ma, Xiaoyu Cheng, Ying Xin, Can Wang, Keke Zhang, Xuefeng Wang, Wei Ren, Ruixia Sun, Zhaotong Jia, Zibin Tian, Qing-Sheng Mi, Changgui Li
The urate oxidase (Uox) gene encodes uricase that in the rodent liver degrades uric acid into allantoin, forming an obstacle for establishing stable mouse models of hyperuricemia. The loss of uricase in humans during primate evolution causes their vulnerability to hyperuricemia. Thus, we generated a Uox-knockout mouse model on a pure C57BL/6J background using the transcription activator-like effector nuclease (TALEN) technique. These Uox-knockout mice spontaneously developed hyperuricemia (over 420 μmol/l) with about 40% survival up to 62 weeks...
July 17, 2017: Kidney International
https://www.readbyqxmd.com/read/28729028/micrornas-as-key-effectors-in-the-p53-network
#20
Frauke Goeman, Sabrina Strano, Giovanni Blandino
The guardian of the genome p53 is embedded in a fine-spun network of MicroRNAs. p53 is able to activate or repress directly the transcription of MicroRNAs that are participating in the tumor-suppressive mission of p53. On the other hand, the expression of p53 is under tight control of MicroRNAs that are either targeting directly p53 or factors that are modifying its protein level or activity. Although the most important function of p53 is suggested to be transcriptional regulation, there are several nontranscriptional functions described...
2017: International Review of Cell and Molecular Biology
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