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https://www.readbyqxmd.com/read/28731031/nlrp9b-a-novel-rna-sensing-inflammasome-complex
#1
Chinh Ngo, Si Ming Man
Inflammasome sensors recognize pathogens and danger signals and assemble an immune signaling complex, which induces the secretion of pro-inflammatory cytokines IL-1β and IL-18, and pyroptosis. A new study published in Nature now describes a new inflammasome sensor NLRP9b in intestinal epithelial cells, which in concert with the RNA sensor DHX9, recognize short dsRNA from Rotavirus.
July 21, 2017: Cell Research
https://www.readbyqxmd.com/read/28731030/cryo-em-structure-and-biochemical-analysis-reveal-the-basis-of-the-functional-difference-between-human-pi3kc3-c1-and-c2
#2
Meisheng Ma, Jun-Jie Liu, Yan Li, Yuwei Huang, Na Ta, Yang Chen, Hua Fu, Ming-Da Ye, Yuehe Ding, Weijiao Huang, Jia Wang, Meng-Qiu Dong, Li Yu, Hong-Wei Wang
Phosphatidylinositol 3-phosphate (PI3P) plays essential roles in vesicular trafficking, organelle biogenesis and autophagy. Two class III phosphatidylinositol 3-kinase (PI3KC3) complexes have been identified in mammals, the ATG14L complex (PI3KC3-C1) and the UVRAG complex (PI3KC3-C2). PI3KC3-C1 is crucial for autophagosome biogenesis, and PI3KC3-C2 is involved in various membrane trafficking events. Here we report the cryo-EM structures of human PI3KC3-C1 and PI3KC3-C2 at sub-nanometer resolution. The two structures share a common L-shaped overall architecture with distinct features...
July 21, 2017: Cell Research
https://www.readbyqxmd.com/read/28707671/cardiomyocyte-proliferation-remove-brakes-and-push-accelerators
#3
Lingjuan He, Bin Zhou
Adult mammalian hearts cannot repair by themselves after injury due to limited proliferation of cardiomyocytes; removal of cell cycle blocker and/or addition of drugs that boost proliferation of cardiomyocytes provide potential means to cardiac regeneration. Three publications that appeared recently in Nature and Cell Research now provide new hope to the treatment of heart injuries.
July 14, 2017: Cell Research
https://www.readbyqxmd.com/read/28695889/coding-gpcr-g-protein-specificity
#4
Sebastian Gb Furness, Patrick M Sexton
G protein-coupled receptors (GPCRs) are ubiquitous gatekeepers of cellular response and signal predominantly by recruitment and activation of G proteins. In a recent paper in Nature, Flock et al. use large-scale bioinformatics to build a model of GPCR-G protein selectivity and an interactive database to interrogate potential receptor-G protein interactions.
July 11, 2017: Cell Research
https://www.readbyqxmd.com/read/28685773/inhibition-of-the-b7-h3-immune-checkpoint-limits-tumor-growth-by-enhancing-cytotoxic-lymphocyte-function
#5
Young-Hee Lee, Natalia Martin-Orozco, Peilin Zheng, Jing Li, Peng Zhang, Haidong Tan, Hyun Jung Park, Mira Jeong, Seon Hee Chang, Byung-Seok Kim, Wei Xiong, Wenjuan Zang, Li Guo, Yang Liu, Zhong-Jun Dong, Willem W Overwijk, Patrick Hwu, Qing Yi, Larry Kwak, Zhiying Yang, Tak W Mak, Wei Li, Laszlo G Radvanyi, Ling Ni, Dongfang Liu, Chen Dong
The interaction between tumor and the immune system is still poorly understood. Significant clinical responses have been achieved in cancer patients treated with antibodies against the CTLA4 and PD-1/PD-L1 checkpoints; however, only a small portion of patients responded to the therapies, indicating a need to explore additional co-inhibitory molecules for cancer treatment. B7-H3, a member of the B7 superfamily, was previously shown by us to inhibit T-cell activation and autoimmunity. In this study, we have analyzed the function of B7-H3 in tumor immunity...
July 7, 2017: Cell Research
https://www.readbyqxmd.com/read/28685772/genetic-enhancement-in-cultured-human-adult-stem-cells-conferred-by-a-single-nucleotide-recoding
#6
Jiping Yang, Jingyi Li, Keiichiro Suzuki, Xiaomeng Liu, Jun Wu, Weiqi Zhang, Ruotong Ren, Weizhou Zhang, Piu Chan, Juan Carlos Izpisua Belmonte, Jing Qu, Fuchou Tang, Guang-Hui Liu
No abstract text is available yet for this article.
July 7, 2017: Cell Research
https://www.readbyqxmd.com/read/28685771/it-takes-two-to-transport-via-an-elevator
#7
Bernadette Byrne
Membrane transporter proteins are critical for cellular uptake and export of molecules, and are reported to function by a number of different molecular mechanisms. The new occluded state structure of the uracil transporter, UraA, from Escherichia coli, reveals that both coordinated movement of the two domains of a single protomer together with dimer formation are important for transport activity.
July 7, 2017: Cell Research
https://www.readbyqxmd.com/read/28685770/existing-drugs-as-broad-spectrum-and-potent-inhibitors-for-zika-virus-by-targeting-ns2b-ns3-interaction
#8
Zhong Li, Matthew Brecher, Yong-Qiang Deng, Jing Zhang, Srilatha Sakamuru, Binbin Liu, Ruili Huang, Cheri A Koetzner, Christina A Allen, Susan A Jones, Haiying Chen, Na-Na Zhang, Min Tian, Fengshan Gao, Qishan Lin, Nilesh Banavali, Jia Zhou, Nathan Boles, Menghang Xia, Laura D Kramer, Cheng-Feng Qin, Hongmin Li
Recent outbreaks of Zika virus (ZIKV) highlight an urgent need for therapeutics. The protease complex NS2B-NS3 plays essential roles during flaviviral polyprotein processing, and thus represents an attractive drug target. Here, we developed a split luciferase complementation-based high-throughput screening assay to identify orthosteric inhibitors that directly target flavivirus NS2B-NS3 interactions. By screening a total of 2 816 approved and investigational drugs, we identified three potent candidates, temoporfin, niclosamide, and nitazoxanide, as flavivirus NS2B-NS3 interaction inhibitors with nanomolar potencies...
July 7, 2017: Cell Research
https://www.readbyqxmd.com/read/28675158/smad5-acts-as-an-intracellular-ph-messenger-and-maintains-bioenergetic-homeostasis
#9
Yujiang Fang, Zhongliang Liu, Zhenyu Chen, Xiangjie Xu, Mengtao Xiao, Yanyan Yu, Yuanyuan Zhang, Xiaobai Zhang, Yanhua Du, Cizhong Jiang, Yuzheng Zhao, Yiran Wang, Beibei Fan, Daniel Terheyden-Keighley, Yang Liu, Lei Shi, Yi Hui, Xin Zhang, Bowen Zhang, Hexi Feng, Lin Ma, Quanbin Zhang, Guohua Jin, Yi Yang, Bin Xiang, Ling Liu, Xiaoqing Zhang
Both environmental cues and intracellular bioenergetic states profoundly affect intracellular pH (pHi). How a cell responds to pHi changes to maintain bioenergetic homeostasis remains elusive. Here we show that Smad5, a well-characterized downstream component of bone morphogenetic protein (BMP) signaling responds to pHi changes. Cold, basic or hypertonic conditions increase pHi, which in turn dissociates protons from the charged amino acid clusters within the MH1 domain of Smad5, prompting its relocation from the nucleus to the cytoplasm...
July 4, 2017: Cell Research
https://www.readbyqxmd.com/read/28621329/single-cell-multi-omics-sequencing-of-mouse-early-embryos-and-embryonic-stem-cells
#10
Fan Guo, Lin Li, Jingyun Li, Xinglong Wu, Boqiang Hu, Ping Zhu, Lu Wen, Fuchou Tang
Single-cell epigenome sequencing techniques have recently been developed. However, the combination of different layers of epigenome sequencing in an individual cell has not yet been achieved. Here, we developed a single-cell multi-omics sequencing technology (single-cell COOL-seq) that can analyze the chromatin state/nucleosome positioning, DNA methylation, copy number variation and ploidy simultaneously from the same individual mammalian cell. We used this method to analyze the reprogramming of the chromatin state and DNA methylation in mouse preimplantation embryos...
June 16, 2017: Cell Research
https://www.readbyqxmd.com/read/28621328/live-cell-screening-platform-identifies-ppar%C3%AE-as-a-regulator-of-cardiomyocyte-proliferation-and-cardiac-repair
#11
Ajit Magadum, Yishu Ding, Lan He, Teayoun Kim, Mohankrishna Dalvoy Vasudevarao, Qinqiang Long, Kevin Yang, Nadeera Wickramasinghe, Harsha V Renikunta, Nicole Dubois, Gilbert Weidinger, Qinglin Yang, Felix B Engel
Zebrafish can efficiently regenerate their heart through cardiomyocyte proliferation. In contrast, mammalian cardiomyocytes stop proliferating shortly after birth, limiting the regenerative capacity of the postnatal mammalian heart. Therefore, if the endogenous potential of postnatal cardiomyocyte proliferation could be enhanced, it could offer a promising future therapy for heart failure patients. Here, we set out to systematically identify small molecules triggering postnatal cardiomyocyte proliferation. By screening chemical compound libraries utilizing a Fucci-based system for assessing cell cycle stages, we identified carbacyclin as an inducer of postnatal cardiomyocyte proliferation...
June 16, 2017: Cell Research
https://www.readbyqxmd.com/read/28621327/dimeric-structure-of-the-uracil-proton-symporter-uraa-provides-mechanistic-insights-into-the-slc4-23-26-transporters
#12
Xinzhe Yu, Guanghui Yang, Chuangye Yan, Javier L Baylon, Jing Jiang, He Fan, Guifeng Lu, Kazuya Hasegawa, Hideo Okumura, Tingliang Wang, Emad Tajkhorshid, Shuo Li, Nieng Yan
The Escherichia coli uracil:proton symporter UraA is a prototypical member of the nucleobase/ascorbate transporter (NAT) or nucleobase/cation symporter 2 (NCS2) family, which corresponds to the human solute carrier family SLC23. UraA consists of 14 transmembrane segments (TMs) that are organized into two distinct domains, the core domain and the gate domain, a structural fold that is also shared by the SLC4 and SLC26 transporters. Here we present the crystal structure of UraA bound to uracil in an occluded state at 2...
June 16, 2017: Cell Research
https://www.readbyqxmd.com/read/28524164/ripped-for-neuroinflammation
#13
Bart Tummers, Douglas R Green
Activation of the receptor interacting serine/threonine kinase (RIPK) 3 mediates an inflammatory type of cell death called necroptosis; in addition, RIPK3 has necroptosis-independent roles in inflammation, although these are not well defined. In a recent study published in Cell, Daniels and colleagues demonstrate that RIPK3 controls West Nile virus infection by promoting neuroinflammation in the central nervous system without affecting neuronal death.
May 19, 2017: Cell Research
https://www.readbyqxmd.com/read/28497811/polar-bodies-are-efficient-donors-for-reconstruction-of-human-embryos-for-potential-mitochondrial-replacement-therapy
#14
Keliang Wu, Cuiqing Zhong, Tailai Chen, Xiaoyu Zhang, Wenrong Tao, Jingye Zhang, Hongchang Li, Han Zhao, Jinsong Li, Zi-Jiang Chen
No abstract text is available yet for this article.
May 12, 2017: Cell Research
https://www.readbyqxmd.com/read/28497809/receptor-like-protein-elt1-promotes-brassinosteroid-signaling-through-interacting-with-and-suppressing-the-endocytosis-mediated-degradation-of-receptor-bri1
#15
Bao-Jun Yang, Wen-Hui Lin, Fang-Fang Fu, Zhi-Hong Xu, Hong-Wei Xue
No abstract text is available yet for this article.
May 12, 2017: Cell Research
https://www.readbyqxmd.com/read/28485368/threading-an-elephant-through-the-eye-of-a-needle-where-are-platelets-made
#16
Ian Johnston, Vincent Hayes, Mortimer Poncz
There has been a long-standing controversy of whether megakaryocytes release platelets in the marrow or travel to the lungs and release platelets there. Using two-photon electron microscopy and orthotopic lung transplantation, Lefrançais et al. now document that platelet release occurs physiologically in the lungs of mice from extrapulmonary megakaryocytes and that this release accounts for ∼50% of total platelet production.
May 9, 2017: Cell Research
https://www.readbyqxmd.com/read/28452344/clonal-analysis-reveals-remarkable-functional-heterogeneity-during-hematopoietic-stem-cell-emergence
#17
Hui Ye, Xiaobo Wang, Zongcheng Li, Fan Zhou, Xianlong Li, Yanli Ni, Weijing Zhang, Fuchou Tang, Bing Liu, Yu Lan
No abstract text is available yet for this article.
April 28, 2017: Cell Research
https://www.readbyqxmd.com/read/28674430/remote-control-of-bbb-a-tale-of-exosomes-and-microrna
#18
Zhen Zhao, Berislav V Zlokovic
Exosome-mediated intercellular communication has become an emerging field of human health and diseases. A recent study published by Cell Research reports that in zebrafish neurons can remotely regulate blood-brain barrier integrity by delivering miR-132 through secretion of exosomes.
July 2017: Cell Research
https://www.readbyqxmd.com/read/28585534/one-step-generation-of-complete-gene-knockout-mice-and-monkeys-by-crispr-cas9-mediated-gene-editing-with-multiple-sgrnas
#19
Erwei Zuo, Yi-Jun Cai, Kui Li, Yu Wei, Bang-An Wang, Yidi Sun, Zhen Liu, Jiwei Liu, Xinde Hu, Wei Wei, Xiaona Huo, Linyu Shi, Cheng Tang, Dan Liang, Yan Wang, Yan-Hong Nie, Chen-Chen Zhang, Xuan Yao, Xing Wang, Changyang Zhou, Wenqin Ying, Qifang Wang, Ren-Chao Chen, Qi Shen, Guo-Liang Xu, Jinsong Li, Qiang Sun, Zhi-Qi Xiong, Hui Yang
The CRISPR/Cas9 system is an efficient gene-editing method, but the majority of gene-edited animals showed mosaicism, with editing occurring only in a portion of cells. Here we show that single gene or multiple genes can be completely knocked out in mouse and monkey embryos by zygotic injection of Cas9 mRNA and multiple adjacent single-guide RNAs (spaced 10-200 bp apart) that target only a single key exon of each gene. Phenotypic analysis of F0 mice following targeted deletion of eight genes on the Y chromosome individually demonstrated the robustness of this approach in generating knockout mice...
July 2017: Cell Research
https://www.readbyqxmd.com/read/28574056/the-dub-blade-goes-snicker-snack-novel-ubiquitin-cleavage-by-a-legionella-effector-protein
#20
Judith A Ronau, Mark Hochstrasser
Recently, a Legionella pneumophila effector protein was shown to have an unprecedented ATP-independent ubiquitin ligase activity that couples phosphoribosylated ubiquitin (PR-Ub) to serine residues of host proteins. A new study published in Cell Research by Qiu et al. reveals that another Legionella effector protein, SidJ, catalyzes deubiquitination of PR-Ub by cleavage of the substrate-linked phosphodiester bond.
July 2017: Cell Research
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