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Cell Discovery

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https://www.readbyqxmd.com/read/29760946/sequence-determinants-of-specific-pattern-recognition-of-bacterial-ligands-by-the-naip-nlrc4-inflammasome
#1
Jingyi Yang, Yue Zhao, Peng Li, Yi Yang, Ejuan Zhang, Maohua Zhong, Yaoming Li, Dihan Zhou, Yuan Cao, Mengji Lu, Feng Shao, Huimin Yan
The NLR apoptosis inhibitory proteins (NAIPs) function as specific cytosolic receptors for bacterial ligands to form the NAIP-NLRC4 inflammasome for anti-bacterial defenses. In mice, NAIP5/6 and NAIP2 recognize bacteria flagellin and the rod protein of the type III secretion system (T3SS), respectively. However, molecular mechanism for specific ligand pattern-recognition by the NAIPs is largely unknown. Here, through extensive domain swapping and truncation analyses, three structural domains, the pre-BIR, BIR1, and HD1, in NAIP2 and NAIP5 are identified, that are important for specific recognition of their respective ligand(s)...
2018: Cell Discovery
https://www.readbyqxmd.com/read/29736258/mtf2-prc2-control-of-canonical-wnt-signaling-is-required-for-definitive-erythropoiesis
#2
Janet L Manias Rothberg, Harinad B Maganti, Hani Jrade, Christopher J Porter, Gareth A Palidwor, Christopher Cafariello, Hannah L Battaion, Safwat T Khan, Theodore J Perkins, Robert F Paulson, Caryn Y Ito, William L Stanford
Polycomb repressive complex 2 (PRC2) accessory proteins play substoichiometric, tissue-specific roles to recruit PRC2 to specific genomic loci or increase enzymatic activity, while PRC2 core proteins are required for complex stability and global levels of trimethylation of histone 3 at lysine 27 (H3K27me3). Here, we demonstrate a role for the classical PRC2 accessory protein Mtf2/Pcl2 in the hematopoietic system that is more akin to that of a core PRC2 protein. Mtf2 -/- erythroid progenitors demonstrate markedly decreased core PRC2 protein levels and a global loss of H3K27me3 at promoter-proximal regions...
2018: Cell Discovery
https://www.readbyqxmd.com/read/29707234/crispr-cas12a-assisted-nucleic-acid-detection
#3
Shi-Yuan Li, Qiu-Xiang Cheng, Jing-Man Wang, Xiao-Yan Li, Zi-Long Zhang, Song Gao, Rui-Bing Cao, Guo-Ping Zhao, Jin Wang
No abstract text is available yet for this article.
2018: Cell Discovery
https://www.readbyqxmd.com/read/29707233/zika-virus-propagation-and-release-in-human-fetal-astrocytes-can-be-suppressed-by-neutral-sphingomyelinase-2-inhibitor-gw4869
#4
Yunlong Huang, Yuju Li, Hainan Zhang, Runze Zhao, Ran Jing, Yinghua Xu, Miao He, Justin Peer, Yeong C Kim, Jiangtao Luo, Zenghan Tong, Jialin Zheng
Zika virus (ZIKV) is a neurotrophic flavivirus that is capable of infecting humans, leading to brain abnormalities during fetal development. The ZIKV infectivity in neural target cells remains poorly understood. Here, we found that ZIKV specifically infected glial fibrillary acidic protein- and S100B-positive primary human astrocytes derived from fetal brains. In contrast, neuron-specific Class III β-tubulin (TuJ1)-positive neurons in the astrocyte cultures and SOX2-positive neural progenitor cells derived from the fetal brains were less susceptible to ZIKV infection compared with astrocytes...
2018: Cell Discovery
https://www.readbyqxmd.com/read/29675267/genetic-variation-may-confound-analysis-of-crispr-cas9-off-target-mutations
#5
Guanqun Wang, Meijie Du, Jianbin Wang, Ting F Zhu
No abstract text is available yet for this article.
2018: Cell Discovery
https://www.readbyqxmd.com/read/29675266/evaluation-of-insulin-sensitivity-by-hyperinsulinemic-euglycemic-clamps-using-stable-isotope-labeled-glucose
#6
Yuanyuan Zhang, Lina Xu, Xiaohui Liu, Yiguo Wang
No abstract text is available yet for this article.
2018: Cell Discovery
https://www.readbyqxmd.com/read/29644094/insufficiency-of-dna-repair-enzyme-atm-promotes-naive-cd4-t-cell-loss-in-chronic-hepatitis-c-virus-infection
#7
Juan Zhao, Xindi Dang, Peixin Zhang, Lam Nhat Nguyen, Dechao Cao, Lin Wang, Xiaoyuan Wu, Zheng D Morrison, Ying Zhang, Zhansheng Jia, Qian Xie, Ling Wang, Shunbin Ning, Mohamed El Gazzar, Jonathan P Moorman, Zhi Q Yao
T cells have a crucial role in viral clearance and vaccine response; however, the mechanisms regulating their responses to viral infections or vaccinations remain elusive. In this study, we investigated T-cell homeostasis, apoptosis, DNA damage, and repair machineries in a large cohort of subjects with hepatitis C virus (HCV) infection. We found that naive CD4 T cells in chronically HCV-infected individuals (HCV T cells) were significantly reduced compared with age-matched healthy subjects. In addition, HCV T cells were prone to apoptosis and DNA damage, as evidenced by increased 8-oxoguanine expression and γH2AX/53BP1-formed DNA damage foci-hallmarks of DNA damage responses...
2018: Cell Discovery
https://www.readbyqxmd.com/read/29619245/selective-deletion-of-ppar%C3%AE-%C3%AE-in-fibroblasts-causes-dermal-fibrosis-by-attenuated-lrg1-expression
#8
Ming Keat Sng, Jeremy Soon Kiat Chan, Ziqiang Teo, Terri Phua, Eddie Han Pin Tan, Jonathan Wei Kiat Wee, Nikki Jun Ning Koh, Chek Kun Tan, Jia Peng Chen, Mintu Pal, Benny Meng Kiat Tong, Ya Lin Tnay, Xuan Rui Ng, Pengcheng Zhu, Shunsuke Chiba, Xiaomeng Wang, Walter Wahli, Nguan Soon Tan
Connective tissue diseases of the skin are characterized by excessive collagen deposition in the skin and internal organs. Fibroblasts play a pivotal role in the clinical presentation of these conditions. Nuclear receptor peroxisome-proliferator activated receptors (PPARs) are therapeutic targets for dermal fibrosis, but the contribution of the different PPAR subtypes are poorly understood. Particularly, the role of fibroblast PPARβ/δ in dermal fibrosis has not been elucidated. Thus, we generated a mouse strain with selective deletion of PPARβ/δ in the fibroblast (FSPCre- Pparb/d -/- ) and interrogated its epidermal and dermal transcriptome profiles...
2018: Cell Discovery
https://www.readbyqxmd.com/read/29619244/antiviral-effects-of-ferric-ammonium-citrate
#9
Hongbin Wang, Zheng Li, Junling Niu, Yongfen Xu, Li Ma, Ailing Lu, Xun Wang, Zhikang Qian, Zhong Huang, Xia Jin, Qibin Leng, Jianhua Wang, Jin Zhong, Bing Sun, Guangxun Meng
Iron is an essential nutrient for cell survival and is crucial for DNA replication, mitochondrial function and erythropoiesis. However, the immunological role of iron in viral infections has not been well defined. Here we found the iron salt ferric ammonium citrate (FAC) inhibited Influenza A virus, HIV virus, Zika virus, and Enterovirus 71 (EV71) infections. Of note, both iron ion and citrate ion were required for the antiviral capability of FAC, as other iron salts and citrates did not exhibit viral inhibition...
2018: Cell Discovery
https://www.readbyqxmd.com/read/29581886/trim29-negatively-controls-antiviral-immune-response-through-targeting-sting-for-degradation
#10
Qijie Li, Liangbin Lin, Yanli Tong, Yantong Liu, Jun Mou, Xiaodong Wang, Xiuxuan Wang, Yanqiu Gong, Yi Zhao, Yi Liu, Bo Zhong, Lunzhi Dai, Yu-Quan We, Huiyuan Zhang, Hongbo Hu
Innate immune system is armed by several lines of pattern recognition receptors to sense various viral infection and to initiate antiviral immune response. This process is under a tight control and the negative feedback induced by infection and/or inflammation is critical to maintain immune homoeostasis and to prevent autoimmune disorders, however, the molecular mechanism is not fully understood. Here we report TRIM29, a ubiquitin E3 ligase, functions as an inducible negative regulator of innate immune response triggered by DNA virus and cytosolic DNA...
2018: Cell Discovery
https://www.readbyqxmd.com/read/29560272/crystal-structure-of-the-human-5-ht-1b-serotonin-receptor-bound-to-an-inverse-agonist
#11
Wanchao Yin, X Edward Zhou, Dehua Yang, Parker W de Waal, Meitian Wang, Antao Dai, Xiaoqing Cai, Chia-Ying Huang, Ping Liu, Xiaoxi Wang, Yanting Yin, Bo Liu, Yu Zhou, Jiang Wang, Hong Liu, Martin Caffrey, Karsten Melcher, Yechun Xu, Ming-Wei Wang, H Eric Xu, Yi Jiang
5-hydroxytryptamine (5-HT, also known as serotonin) regulates many physiological processes through the 5-HT receptor family. Here we report the crystal structure of 5-HT1B subtype receptor (5-HT1B R) bound to the psychotropic serotonin receptor inverse agonist methiothepin (MT). Crystallization was facilitated by replacing ICL3 with a novel optimized variant of BRIL (OB1) that enhances the formation of intermolecular polar interactions, making OB1 a potential useful tool for structural studies of membrane proteins...
2018: Cell Discovery
https://www.readbyqxmd.com/read/29531792/dnajc5-facilitates-usp19-dependent-unconventional-secretion-of-misfolded-cytosolic-proteins
#12
Yue Xu, Lei Cui, Anthony Dibello, Lihui Wang, Juhyung Lee, Layla Saidi, Jin-Gu Lee, Yihong Ye
Cell-to-cell transmission of misfolded proteins propagates proteotoxic stress in multicellular organisms when transmitted polypeptides serve as a seeding template to cause protein misfolding in recipient cells, but how misfolded proteins are released from cells to initiate this process is unclear. Misfolding-associated protein secretion (MAPS) is an unconventional protein-disposing mechanism that specifically exports misfolded cytosolic proteins including various neurodegenerative disease-causing proteins. Here we establish the HSC70 co-chaperone DNAJC5 as an essential mediator of MAPS...
2018: Cell Discovery
https://www.readbyqxmd.com/read/29507755/virma-mediates-preferential-m-6-a-mrna-methylation-in-3-utr-and-near-stop-codon-and-associates-with-alternative-polyadenylation
#13
Yanan Yue, Jun Liu, Xiaolong Cui, Jie Cao, Guanzheng Luo, Zezhou Zhang, Tao Cheng, Minsong Gao, Xiao Shu, Honghui Ma, Fengqin Wang, Xinxia Wang, Bin Shen, Yizhen Wang, Xinhua Feng, Chuan He, Jianzhao Liu
N 6 -methyladenosine (m6 A) is enriched in 3'untranslated region (3'UTR) and near stop codon of mature polyadenylated mRNAs in mammalian systems and has regulatory roles in eukaryotic mRNA transcriptome switch. Significantly, the mechanism for this modification preference remains unknown, however. Herein we report a characterization of the full m6 A methyltransferase complex in HeLa cells identifying METTL3/METTL14/WTAP/VIRMA/HAKAI/ZC3H13 as the key components, and we show that VIRMA mediates preferential mRNA methylation in 3'UTR and near stop codon...
2018: Cell Discovery
https://www.readbyqxmd.com/read/29507754/dual-extra-retinal-origins-of-microglia-in-the-model-of-retinal-microglia-repopulation
#14
Yubin Huang, Zhen Xu, Shanshan Xiong, Guangrong Qin, Fangfang Sun, Jian Yang, Ti-Fei Yuan, Lei Zhao, Ke Wang, Yu-Xiang Liang, Lin Fu, Tianzhun Wu, Kwok-Fai So, Yanxia Rao, Bo Peng
Elucidating the origin of microglia is crucial for understanding their functions and homeostasis. Previous study has indicated that Nestin-positive progenitor cells differentiate into microglia and replenish the brain after depleting most brain microglia. Microglia have also shown the capacity to repopulate the retina after eliminating all retinal microglia. However, the origin(s) of repopulated retinal microglia is/are unknown. In this study, we aim to investigate the origins of repopulated microglia in the retina...
2018: Cell Discovery
https://www.readbyqxmd.com/read/29507753/long-non-coding-rna-mt1dp-shunts-the-cellular-defense-to-cytotoxicity-through-crosstalk-with-mt1h-and-rhoc-in-cadmium-stress
#15
Ming Gao, Minjun Chen, Changying Li, Ming Xu, Yun Liu, Min Cong, Nan Sang, Sijin Liu
Metallothioneins (MTs) are known to protect cells against oxidative stress, especially providing protection against cadmium (Cd) toxicity in hepatocytes. There are various gene variants and pseudogenes for MTs; however, there is little understanding on the functions of those non-coding MT members that are known to be expressed as long non-coding RNAs (lncRNAs) nowadays. Different from most protein-coding MT members, MT1DP was here found that remarkably induced to provoke cytotoxicity in hepatocytes in response to Cd treatment...
2018: Cell Discovery
https://www.readbyqxmd.com/read/29479476/the-binding-of-dcc-p3-motif-and-fak-fat-domain-mediates-the-initial-step-of-netrin-1-dcc-signaling-for-axon-attraction
#16
Shutong Xu, Yiqiong Liu, Xiaolong Li, Ying Liu, Rob Meijers, Yan Zhang, Jia-Huai Wang
Netrin-1 plays a key role in axon guidance through binding to its receptor, Deleted in Colorectal Cancer (DCC). The initial step of signaling inside the cell after netrin-1/DCC ligation is the binding of DCC cytoplasmic P3 motif to focal adhesion targeting (FAT) domain of focal adhesion kinase (FAK). Here we report the crystal structure of P3/FAT complex. The helical P3 peptide interacts with a helix-swapped FAT dimer in a 2:2 ratio. Dimeric FAT binding is P3-specific and stabilized by a calcium ion. Biochemical studies showed that DCC-P3 motif and calcium ion could facilitate FAT dimerization in solution...
2018: Cell Discovery
https://www.readbyqxmd.com/read/29449961/cadherin-26-cdh26-regulates-airway-epithelial-cell-cytoskeletal-structure-and-polarity
#17
Marrah E Lachowicz-Scroggins, Erin D Gordon, Agata Wesolowska-Andersen, Nathan D Jackson, Hannah J MacLeod, Louis Z Sharp, Matthew Sun, Max A Seibold, John V Fahy
Polarization of the airway epithelial cells (AECs) in the airway lumen is critical to the proper function of the mucociliary escalator and maintenance of lung health, but the cellular requirements for polarization of AECs are poorly understood. Using human AECs and cell lines, we demonstrate that cadherin-26 (CDH26) is abundantly expressed in differentiated AECs, localizes to the cell apices near ciliary membranes, and has functional cadherin domains with homotypic binding. We find a unique and non-redundant role for CDH26, previously uncharacterized in AECs, in regulation of cell-cell contact and cell integrity through maintaining cytoskeletal structures...
2018: Cell Discovery
https://www.readbyqxmd.com/read/29423273/cd24-p53-axis-suppresses-diethylnitrosamine-induced-hepatocellular-carcinogenesis-by-sustaining-intrahepatic-macrophages
#18
Dongling Li, Minling Hu, Ying Liu, Peiying Ye, Peishuang Du, Chi-Shan Li, Liang Cheng, Ping Liu, Jing Jiang, Lishan Su, Shengdian Wang, Pan Zheng, Yang Liu
It is generally assumed that inflammation following diethylnitrosamine (DEN) treatment promotes development of hepatocellular carcinoma (HCC) through the activity of intrahepatic macrophages. However, the tumor-promoting function of macrophages in the model has not been confirmed by either macrophage depletion or selective gene depletion in macrophages. Here we show that targeted mutation of Cd24 dramatically increased HCC burden while reducing intrahepatic macrophages and DEN-induced hepatocyte apoptosis. Depletion of macrophages also increased HCC burden and reduced hepatocyte apoptosis, thus establishing macrophages as an innate effector recognizing DEN-induced damaged hepatocytes...
2018: Cell Discovery
https://www.readbyqxmd.com/read/29423272/loss-of-asxl1-in-the-bone-marrow-niche-dysregulates-hematopoietic-stem-and-progenitor-cell-fates
#19
Peng Zhang, Zizhen Chen, Rong Li, Ying Guo, Hui Shi, Jie Bai, Hui Yang, Mengyao Sheng, Zhaomin Li, Zhuo Li, Jianping Li, Shi Chen, Weiping Yuan, Tao Cheng, Mingjiang Xu, Yuan Zhou, Feng-Chun Yang
Somatic or de novo mutations of Additional sex combs-like 1 ( ASXL1 ) frequently occur in patients with myeloid malignancies or Bohring-Opitz syndrome, respectively. We have reported that global loss of Asxl1 leads to the development of myeloid malignancies and impairs bone marrow stromal cell (BMSC) fates in mice. However, the impact of Asxl1 deletion in the BM niche on hematopoiesis remains unclear. Here, we showed that BMSCs derived from chronic myelomonocytic leukemia patients had reduced expression of ASXL1 , which impaired the maintaining cord blood CD34+ cell colony-forming capacity with a myeloid differentiation bias...
2018: Cell Discovery
https://www.readbyqxmd.com/read/29423271/dual-roles-of-endothelial-fgf-2-fgfr1-pdgf-bb-and-perivascular-fgf-2-fgfr2-pdgfr%C3%AE-signaling-pathways-in-tumor-vascular-remodeling
#20
Kayoko Hosaka, Yunlong Yang, Masaki Nakamura, Patrik Andersson, Xiaojuan Yang, Yin Zhang, Takahiro Seki, Martin Scherzer, Olivier Dubey, Xinsheng Wang, Yihai Cao
Perivascular cells are important cellular components in the tumor microenvironment (TME) and they modulate vascular integrity, remodeling, stability, and functions. Here we show using mice models that FGF-2 is a potent pericyte-stimulating factor in tumors. Mechanistically, FGF-2 binds to FGFR2 to stimulate pericyte proliferation and orchestrates the PDGFRβ signaling for vascular recruitment. FGF-2 sensitizes the PDGFRβ signaling through increasing PDGFRβ levels in pericytes. To ensure activation of PDGFRβ, the FGF-2-FGFR1-siganling induces PDGF-BB and PDGF-DD, two ligands for PDGFRβ, in angiogenic endothelial cells...
2018: Cell Discovery
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