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Cell Reports

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https://www.readbyqxmd.com/read/29456100/the-coding-regions-of-germline-mrnas-confer-sensitivity-to-argonaute-regulation-in-c-elegans
#1
Meetu Seth, Masaki Shirayama, Wen Tang, En-Zhi Shen, Shikui Tu, Heng-Chi Lee, Zhiping Weng, Craig C Mello
Protein-coding genes undergo a wide array of regulatory interactions with factors that engage non-coding regions. Open reading frames (ORFs), in contrast, are thought to be constrained by coding function, precluding a major role in gene regulation. Here, we explore Piwi-interacting (pi)RNA-mediated transgene silencing in C. elegans and show that marked differences in the sensitivity to piRNA silencing map to the endogenous sequences within transgene ORFs. Artificially increasing piRNA targeting within the ORF of a resistant transgene can lead to a partial yet stable reduction in expression, revealing that piRNAs not only silence but can also "tune" gene expression...
February 14, 2018: Cell Reports
https://www.readbyqxmd.com/read/29669295/a-quantitative-chemotherapy-genetic-interaction-map-reveals-factors-associated-with-parp-inhibitor-resistance
#2
Hsien-Ming Hu, Xin Zhao, Swati Kaushik, Lilliane Robillard, Antoine Barthelet, Kevin K Lin, Khyati N Shah, Andy D Simmons, Mitch Raponi, Thomas C Harding, Sourav Bandyopadhyay
Chemotherapy is used to treat most cancer patients, yet our understanding of factors that dictate response and resistance to such drugs remains limited. We report the generation of a quantitative chemical-genetic interaction map in human mammary epithelial cells charting the impact of the knockdown of 625 genes related to cancer and DNA repair on sensitivity to 29 drugs, covering all classes of chemotherapy. This quantitative map is predictive of interactions maintained in other cell lines, identifies DNA-repair factors, predicts cancer cell line responses to therapy, and prioritizes synergistic drug combinations...
April 17, 2018: Cell Reports
https://www.readbyqxmd.com/read/29669294/a-gene-constellation-in-avian-influenza-a-h7n9-viruses-may-have-facilitated-the-fifth-wave-outbreak-in-china
#3
Wenfei Zhu, Jie Dong, Ye Zhang, Lei Yang, Xiyan Li, Tao Chen, Xiang Zhao, Hejiang Wei, Hong Bo, Xiaoxu Zeng, Weijuan Huang, Zi Li, Jing Tang, Jianfang Zhou, Rongbao Gao, Li Xin, Jing Yang, Shumei Zou, Wenbing Chen, Jia Liu, Yuelong Shu, Dayan Wang
The 2016-2017 epidemic of influenza A (H7N9) virus in China prompted concern that a genetic change may underlie increased virulence. Based on an evolutionary analysis of H7N9 viruses from all five outbreak waves, we find that additional subclades of the H7 and N9 genes have emerged. Our analysis indicates that H7N9 viruses inherited NP genes from co-circulating H7N9 instead of H9N2 viruses. Genotypic diversity among H7N9 viruses increased following wave I, peaked during wave III, and rapidly deceased thereafter with minimal diversity in wave V, suggesting that the viruses entered a relatively stable evolutionary stage...
April 17, 2018: Cell Reports
https://www.readbyqxmd.com/read/29669293/three-dimensional-human-ipsc-derived-artificial-skeletal-muscles-model-muscular-dystrophies-and-enable-multilineage-tissue-engineering
#4
Sara Martina Maffioletti, Shilpita Sarcar, Alexander B H Henderson, Ingra Mannhardt, Luca Pinton, Louise Anne Moyle, Heather Steele-Stallard, Ornella Cappellari, Kim E Wells, Giulia Ferrari, Jamie S Mitchell, Giulia E Tyzack, Vassilios N Kotiadis, Moustafa Khedr, Martina Ragazzi, Weixin Wang, Michael R Duchen, Rickie Patani, Peter S Zammit, Dominic J Wells, Thomas Eschenhagen, Francesco Saverio Tedesco
Generating human skeletal muscle models is instrumental for investigating muscle pathology and therapy. Here, we report the generation of three-dimensional (3D) artificial skeletal muscle tissue from human pluripotent stem cells, including induced pluripotent stem cells (iPSCs) from patients with Duchenne, limb-girdle, and congenital muscular dystrophies. 3D skeletal myogenic differentiation of pluripotent cells was induced within hydrogels under tension to provide myofiber alignment. Artificial muscles recapitulated characteristics of human skeletal muscle tissue and could be implanted into immunodeficient mice...
April 17, 2018: Cell Reports
https://www.readbyqxmd.com/read/29669292/parn-and-toe1-constitute-a-3-end-maturation-module-for-nuclear-non-coding-rnas
#5
Ahyeon Son, Jong-Eun Park, V Narry Kim
Poly(A)-specific ribonuclease (PARN) and target of EGR1 protein 1 (TOE1) are nuclear granule-associated deadenylases, whose mutations are linked to multiple human diseases. Here, we applied mTAIL-seq and RNA sequencing (RNA-seq) to systematically identify the substrates of PARN and TOE1 and elucidate their molecular functions. We found that PARN and TOE1 do not modulate the length of mRNA poly(A) tails. Rather, they promote the maturation of nuclear small non-coding RNAs (ncRNAs). PARN and TOE1 act redundantly on some ncRNAs, most prominently small Cajal body-specific RNAs (scaRNAs)...
April 17, 2018: Cell Reports
https://www.readbyqxmd.com/read/29669291/a-cyfip2-dependent-excitatory-interneuron-pathway-establishes-the-innate-startle-threshold
#6
Kurt C Marsden, Roshan A Jain, Marc A Wolman, Fabio A Echeverry, Jessica C Nelson, Katharina E Hayer, Ben Miltenberg, Alberto E Pereda, Michael Granato
Sensory experiences dynamically modify whether animals respond to a given stimulus, but it is unclear how innate behavioral thresholds are established. Here, we identify molecular and circuit-level mechanisms underlying the innate threshold of the zebrafish startle response. From a forward genetic screen, we isolated five mutant lines with reduced innate startle thresholds. Using whole-genome sequencing, we identify the causative mutation for one line to be in the fragile X mental retardation protein (FMRP)-interacting protein cyfip2...
April 17, 2018: Cell Reports
https://www.readbyqxmd.com/read/29669290/non-canonical-opioid-signaling-inhibits-itch-transmission-in-the-spinal-cord-of-mice
#7
Admire Munanairi, Xian-Yu Liu, Devin M Barry, Qianyi Yang, Jun-Bin Yin, Hua Jin, Hui Li, Qing-Tao Meng, Jia-Hang Peng, Zhen-Yu Wu, Jun Yin, Xuan-Yi Zhou, Li Wan, Ping Mo, Seungil Kim, Fu-Quan Huo, Joseph Jeffry, Yun-Qing Li, Rita Bardoni, Michael R Bruchas, Zhou-Feng Chen
Chronic itch or pruritus is a debilitating disorder that is refractory to conventional anti-histamine treatment. Kappa opioid receptor (KOR) agonists have been used to treat chronic itch, but the underlying mechanism remains elusive. Here, we find that KOR and gastrin-releasing peptide receptor (GRPR) overlap in the spinal cord, and KOR activation attenuated GRPR-mediated histamine-independent acute and chronic itch in mice. Notably, canonical KOR-mediated Gαi signaling is not required for desensitizing GRPR function...
April 17, 2018: Cell Reports
https://www.readbyqxmd.com/read/29669289/usp9x-limits-mitotic-checkpoint-complex-turnover-to-strengthen-the-spindle-assembly-checkpoint-and-guard-against-chromosomal-instability
#8
Agnieszka Skowyra, Lindsey A Allan, Adrian T Saurin, Paul R Clarke
Faithful chromosome segregation during mitosis depends on the spindle assembly checkpoint (SAC), which delays progression through mitosis until every chromosome has stably attached to spindle microtubules via the kinetochore. We show here that the deubiquitinase USP9X strengthens the SAC by antagonizing the turnover of the mitotic checkpoint complex produced at unattached kinetochores. USP9X thereby opposes activation of anaphase-promoting complex/cyclosome (APC/C) and specifically inhibits the mitotic degradation of SAC-controlled APC/C substrates...
April 17, 2018: Cell Reports
https://www.readbyqxmd.com/read/29669288/mutual-stabilization-between-trim9-short-isoform-and-mkk6-potentiates-p38-signaling-to-synergistically-suppress-glioblastoma-progression
#9
Kunpeng Liu, Chuanxia Zhang, Bowen Li, Weihong Xie, Jindong Zhang, Xichen Nie, Peng Tan, Limin Zheng, Song Wu, Yunfei Qin, Jun Cui, Feng Zhi
p38 signaling is broadly involved in controlling inflammation and stress-induced cell death; however, the mechanisms controlling its activity have seldom been studied. Here, we report that TRIM9 short isoform (TRIM9s) potentiates p38 signaling by stabilizing MKK6. Mechanistic studies revealed that TRIM9s promotes the K63-linked ubiquitination of MKK6 at Lys82, thus inhibiting the degradative K48-linked ubiquitination of MKK6 at the same lysine. MKK6 could also stabilize TRIM9s by promoting the phosphorylation of TRIM9s at Ser76/80 via p38, thereby blocking the ubiquitin-proteasome pathway...
April 17, 2018: Cell Reports
https://www.readbyqxmd.com/read/29669287/zranb1-is-an-ezh2-deubiquitinase-and-a-potential-therapeutic-target-in-breast-cancer
#10
Peijing Zhang, Zhenna Xiao, Shouyu Wang, Mutian Zhang, Yongkun Wei, Qinglei Hang, Jongchan Kim, Fan Yao, Cristian Rodriguez-Aguayo, Baochau N Ton, Minjung Lee, Yumeng Wang, Zhicheng Zhou, Liyong Zeng, Xiaoyu Hu, Sarah E Lawhon, Ashley N Siverly, Xiaohua Su, Jia Li, Xiaoping Xie, Xuhong Cheng, Liang-Chiu Liu, Hui-Wen Chang, Shu-Fen Chiang, Gabriel Lopez-Berestein, Anil K Sood, Junjie Chen, M James You, Shao-Cong Sun, Han Liang, Yun Huang, Xianbin Yang, Deqiang Sun, Yutong Sun, Mien-Chie Hung, Li Ma
Although EZH2 enzymatic inhibitors have shown antitumor effects in EZH2-mutated lymphoma and ARID1A-mutated ovarian cancer, many cancers do not respond because EZH2 can promote cancer independently of its histone methyltransferase activity. Here we identify ZRANB1 as the EZH2 deubiquitinase. ZRANB1 binds, deubiquitinates, and stabilizes EZH2. Depletion of ZRANB1 in breast cancer cells results in EZH2 destabilization and growth inhibition. Systemic delivery of ZRANB1 small interfering RNA (siRNA) leads to marked antitumor and antimetastatic effects in preclinical models of triple-negative breast cancer (TNBC)...
April 17, 2018: Cell Reports
https://www.readbyqxmd.com/read/29669286/platelets-promote-metastasis-via-binding-tumor-cd97-leading-to-bidirectional-signaling-that-coordinates-transendothelial-migration
#11
Yvona Ward, Ross Lake, Farhoud Faraji, Jamie Sperger, Philip Martin, Cameron Gilliard, Kimberly P Ku, Tamara Rodems, David Niles, Heather Tillman, JuanJuan Yin, Kent Hunter, Adam G Sowalsky, Joshua Lang, Kathleen Kelly
Tumor cells initiate platelet activation leading to the secretion of bioactive molecules, which promote metastasis. Platelet receptors on tumors have not been well-characterized, resulting in a critical gap in knowledge concerning platelet-promoted metastasis. We identify a direct interaction between platelets and tumor CD97 that stimulates rapid bidirectional signaling. CD97, an adhesion G protein-coupled receptor (GPCR), is an overexpressed tumor antigen in several cancer types. Purified CD97 extracellular domain or tumor cell-associated CD97 stimulated platelet activation...
April 17, 2018: Cell Reports
https://www.readbyqxmd.com/read/29669285/kap1-regulates-regulatory-t-cell-function-and-proliferation-in-both-foxp3-dependent-and-independent-manners
#12
Shigeru Tanaka, Christian Pfleger, Jen-Feng Lai, Florence Roan, Shao-Cong Sun, Steven F Ziegler
Regulatory T cells (Tregs) are indispensable for the establishment of tolerance of self-antigens in animals. The transcriptional regulator Foxp3 is critical for Treg development and function, controlling the expression of genes important for Tregs through interactions with binding partners. We previously reported KAP1 as a binding partner of FOXP3 in human Tregs, but the mechanisms by which KAP1 affects Treg function were unclear. In this study, we analyzed mice with Treg-specific deletion of KAP1 and found that they develop spontaneous autoimmune disease...
April 17, 2018: Cell Reports
https://www.readbyqxmd.com/read/29669284/manifold-roles-of-ccr7-and-its-ligands-in-the-induction-and-maintenance-of-bronchus-associated-lymphoid-tissue
#13
Henrike Fleige, Berislav Bosnjak, Marc Permanyer, Jasmin Ristenpart, Anja Bubke, Stefanie Willenzon, Gerd Sutter, Sanjiv A Luther, Reinhold Förster
The processes underlying the development and maintenance of tertiary lymphoid organs are incompletely understood. Using a Ccr7 knockout/knockin approach, we show that spontaneous bronchus-associated lymphoid tissue (BALT) formation can be caused by CCR7-mediated migration defects of dendritic cells (DCs) in the lung. Plt/plt mice that lack the CCR7 ligands CCL19 and CCL21-serine do not form BALT spontaneously because lung-expressed CCL21-leucine presumably suffices to maintain steady-state DC egress. However, plt/plt mice are highly susceptible to modified vaccinia virus infection, showing enhanced recruitment of immune cells as well as alterations in CCR7-ligand-mediated lymphocyte egress from the lungs, leading to dramatically enhanced BALT...
April 17, 2018: Cell Reports
https://www.readbyqxmd.com/read/29669283/induction-and-maintenance-of-cx3cr1-intermediate-peripheral-memory-cd8-t-cells-by-persistent-viruses-and-vaccines
#14
Claire Louse Gordon, Lian Ni Lee, Leo Swadling, Claire Hutchings, Madeleine Zinser, Andrew John Highton, Stefania Capone, Antonella Folgori, Eleanor Barnes, Paul Klenerman
The induction and maintenance of T cell memory is critical to the success of vaccines. A recently described subset of memory CD8+ T cells defined by intermediate expression of the chemokine receptor CX3CR1 was shown to have self-renewal, proliferative, and tissue-surveillance properties relevant to vaccine-induced memory. We tracked these cells when memory is sustained at high levels: memory inflation induced by cytomegalovirus (CMV) and adenovirus-vectored vaccines. In mice, both CMV and vaccine-induced inflationary T cells showed sustained high levels of CX3R1int cells exhibiting an effector-memory phenotype, characteristic of inflationary pools, in early memory...
April 17, 2018: Cell Reports
https://www.readbyqxmd.com/read/29669282/an-unusual-prohibitin-regulates-malaria-parasite-mitochondrial-membrane-potential
#15
Joachim Michael Matz, Christian Goosmann, Kai Matuschewski, Taco Wilhelmus Antonius Kooij
Proteins of the stomatin/prohibitin/flotillin/HfIK/C (SPFH) family are membrane-anchored and perform diverse cellular functions in different organelles. Here, we investigate the SPFH proteins of the murine malaria model parasite Plasmodium berghei, the conserved prohibitin 1, prohibitin 2, and stomatin-like protein and an unusual prohibitin-like protein (PHBL). The SPFH proteins localize to the parasite mitochondrion. While the conserved family members could not be deleted from the Plasmodium genome, PHBL was successfully ablated, resulting in impaired parasite fitness and attenuated virulence in the mammalian host...
April 17, 2018: Cell Reports
https://www.readbyqxmd.com/read/29669281/differential-reliance-on-lipid-metabolism-as-a-salvage-pathway-underlies-functional-differences-of-t-cell-subsets-in-poor-nutrient-environments
#16
Christopher Ecker, Lili Guo, Stefana Voicu, Luis Gil-de-Gómez, Andrew Medvec, Luis Cortina, Jackie Pajda, Melanie Andolina, Maria Torres-Castillo, Jennifer L Donato, Sarya Mansour, Evan R Zynda, Pei-Yi Lin, Angel Varela-Rohena, Ian A Blair, James L Riley
T cells compete with malignant cells for limited nutrients within the solid tumor microenvironment. We found that effector memory CD4 T cells respond distinctly from other T cell subsets to limiting glucose and can maintain high levels of interferon-γ (IFN-γ) production in a nutrient-poor environment. Unlike naive (TN ) or central memory T (TCM ) cells, effector memory T (TEM ) cells fail to upregulate fatty acid synthesis, oxidative phosphorylation, and reductive glutaminolysis in limiting glucose. Interference of fatty acid synthesis in naive T cells dramatically upregulates IFN-γ, while increasing exogenous lipids in media inhibits production of IFN-γ by all subsets, suggesting that relative ratio of fatty acid metabolism to glycolysis is a direct predictor of T cell effector activity...
April 17, 2018: Cell Reports
https://www.readbyqxmd.com/read/29669280/the-long-non-coding-rna-lnc-31-interacts-with-rock1-mrna-and-mediates-its-yb-1-dependent-translation
#17
Dacia Dimartino, Alessio Colantoni, Monica Ballarino, Julie Martone, Davide Mariani, Johannes Danner, Astrid Bruckmann, Gunter Meister, Mariangela Morlando, Irene Bozzoni
Cytoplasmic long non-coding RNAs have been shown to act at many different levels to control post-transcriptional gene expression, although their role in translational control is poorly understood. Here, we show that lnc-31, a non-coding RNA required for myoblast proliferation, promotes ROCK1 protein synthesis by stabilizing its translational activator, YB-1. We find that lnc-31 binds to the Rock1 mRNA as well as to the YB-1 protein and that translational activation requires physical interaction between the two RNA species...
April 17, 2018: Cell Reports
https://www.readbyqxmd.com/read/29669279/prediction-of-reach-goals-in-depth-and-direction-from-the-parietal-cortex
#18
Matteo Filippini, Rossella Breveglieri, Kostas Hadjidimitrakis, Annalisa Bosco, Patrizia Fattori
The posterior parietal cortex is well known to mediate sensorimotor transformations during the generation of movement plans, but its ability to control prosthetic limbs in 3D environments has not yet been fully demonstrated. With this aim, we trained monkeys to perform reaches to targets located at various depths and directions and tested whether the reach goal position can be extracted from parietal signals. The reach goal location was reliably decoded with accuracy close to optimal (>90%), and this occurred also well before movement onset...
April 17, 2018: Cell Reports
https://www.readbyqxmd.com/read/29669278/sarm1-myd88-5-regulates-neuronal-intrinsic-immune-response-to-traumatic-axonal-injuries
#19
Qi Wang, Shan Zhang, Tingting Liu, Huanhuan Wang, Kaili Liu, Qiujun Wang, Wenwen Zeng
Traumatic injuries can trigger inflammatory reactions, leading to profound neuropathological consequences. However, the immune capacity of neurons, distinct from that of immune cells or glial cells, in response to traumatic insults remains to be fully characterized. In this study, we demonstrate that neurons can detect, cell autonomously, distant axonal damage, resulting in rapid production of a specific collection of cytokines and chemokines. This neuronal immune response appears spatially and temporally separated from injury-induced axon degeneration...
April 17, 2018: Cell Reports
https://www.readbyqxmd.com/read/29669277/modulation-of-tau-isoforms-imbalance-precludes-tau-pathology-and-cognitive-decline-in-a-mouse-model-of-tauopathy
#20
Sonia Lorena Espíndola, Ana Damianich, Rodrigo Javier Alvarez, Manuela Sartor, Juan Emilio Belforte, Juan Esteban Ferrario, Jean-Marc Gallo, María Elena Avale
The microtubule-associated protein tau regulates myriad neuronal functions, such as microtubule dynamics, axonal transport and neurite outgrowth. Tauopathies are neurodegenerative disorders characterized by the abnormal metabolism of tau, which accumulates as insoluble neuronal deposits. The adult human brain contains equal amounts of tau isoforms with three (3R) or four (4R) repeats of microtubule-binding domains, derived from the alternative splicing of exon 10 (E10) in the tau transcript. Several tauopathies are associated with imbalances of tau isoforms, due to splicing deficits...
April 17, 2018: Cell Reports
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