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Cell Reports

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https://www.readbyqxmd.com/read/28228270/torc1-inhibits-gsk3-mediated-elo2-phosphorylation-to-regulate-very-long-chain-fatty-acid-synthesis-and-autophagy
#1
Christine Zimmermann, Aline Santos, Kenneth Gable, Sharon Epstein, Charulatha Gururaj, Pierre Chymkowitch, Dennis Pultz, Steven V Rødkær, Lorena Clay, Magnar Bjørås, Yves Barral, Amy Chang, Nils J Færgeman, Teresa M Dunn, Howard Riezman, Jorrit M Enserink
No abstract text is available yet for this article.
February 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28228269/diverse-central-projection-patterns-of-retinal-ganglion-cells
#2
Emily M Martersteck, Karla E Hirokawa, Mariah Evarts, Amy Bernard, Xin Duan, Yang Li, Lydia Ng, Seung W Oh, Benjamin Ouellette, Joshua J Royall, Michelle Stoecklin, Quanxin Wang, Hongkui Zeng, Joshua R Sanes, Julie A Harris
Understanding how >30 types of retinal ganglion cells (RGCs) in the mouse retina each contribute to visual processing in the brain will require more tools that label and manipulate specific RGCs. We screened and analyzed retinal expression of Cre recombinase using 88 transgenic driver lines. In many lines, Cre was expressed in multiple RGC types and retinal cell classes, but several exhibited more selective expression. We comprehensively mapped central projections from RGCs labeled in 26 Cre lines using viral tracers, high-throughput imaging, and a data processing pipeline...
February 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28228268/er-stress-protein-chop-mediates-insulin-resistance-by-modulating-adipose-tissue-macrophage-polarity
#3
Toru Suzuki, Junhong Gao, Yasushi Ishigaki, Keiichi Kondo, Shojiro Sawada, Tomohito Izumi, Kenji Uno, Keizo Kaneko, Sohei Tsukita, Kei Takahashi, Atsuko Asao, Naoto Ishii, Junta Imai, Tetsuya Yamada, Seiichi Oyadomari, Hideki Katagiri
Obesity represents chronic inflammatory states promoted by pro-inflammatory M1-macrophage infiltration into white adipose tissue (WAT), thereby inducing insulin resistance. Herein, we demonstrate the importance of an ER stress protein, CHOP, in determining adipose tissue macrophage (ATM) polarity and systemic insulin sensitivity. A high-fat diet (HFD) enhances ER stress with CHOP upregulation in adipocytes. CHOP deficiency prevents HFD-induced insulin resistance and glucose intolerance with ATM M2 predomination and Th2 cytokine upregulation in WAT...
February 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28228267/nrf2-improves-leptin-and-insulin-resistance-provoked-by-hypothalamic-oxidative-stress
#4
Yoko Yagishita, Akira Uruno, Toshiaki Fukutomi, Ritsumi Saito, Daisuke Saigusa, Jingbo Pi, Akiyoshi Fukamizu, Fumihiro Sugiyama, Satoru Takahashi, Masayuki Yamamoto
The relationship between loss of hypothalamic function and onset of diabetes mellitus remains elusive. Therefore, we generated a targeted oxidative-stress murine model utilizing conditional knockout (KO) of selenocysteine-tRNA (Trsp) using rat-insulin-promoter-driven-Cre (RIP-Cre). These Trsp-KO (Trsp(RIP)KO) mice exhibit deletion of Trsp in both hypothalamic cells and pancreatic β cells, leading to increased hypothalamic oxidative stress and severe insulin resistance. Leptin signals are suppressed, and numbers of proopiomelanocortin-positive neurons in the hypothalamus are decreased...
February 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28228266/rapid-state-dependent-alteration-in-kv3-channel-availability-drives-flexible-synaptic-signaling-dependent-on-somatic-subthreshold-depolarization
#5
Matthew J M Rowan, Jason M Christie
In many neurons, subthreshold depolarization in the soma can transiently increase action-potential (AP)-evoked neurotransmission via analog-to-digital facilitation. The mechanisms underlying this form of short-term synaptic plasticity are unclear, in part, due to the relative inaccessibility of the axon to direct physiological interrogation. Using voltage imaging and patch-clamp recording from presynaptic boutons of cerebellar stellate interneurons, we observed that depolarizing somatic potentials readily spread into the axon, resulting in AP broadening, increased spike-evoked Ca(2+) entry, and enhanced neurotransmission strength...
February 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28228265/e3-ligase-rnf126-directly-ubiquitinates-frataxin-promoting-its-degradation-identification-of-a-potential-therapeutic-target-for-friedreich-ataxia
#6
Monica Benini, Silvia Fortuni, Ivano Condò, Giulia Alfedi, Florence Malisan, Nicola Toschi, Dario Serio, Damiano Sergio Massaro, Gaetano Arcuri, Roberto Testi, Alessandra Rufini
Friedreich ataxia (FRDA) is a severe genetic neurodegenerative disease caused by reduced expression of the mitochondrial protein frataxin. To date, there is no therapy to treat this condition. The amount of residual frataxin critically affects the severity of the disease; thus, attempts to restore physiological frataxin levels are considered therapeutically relevant. Frataxin levels are controlled by the ubiquitin-proteasome system; therefore, inhibition of the frataxin E3 ligase may represent a strategy to achieve an increase in frataxin levels...
February 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28228264/lsd1-controls-timely-myod-expression-via-myod-core-enhancer-transcription
#7
Isabella Scionti, Shinichiro Hayashi, Sandrine Mouradian, Emmanuelle Girard, Joana Esteves de Lima, Véronique Morel, Thomas Simonet, Maud Wurmser, Pascal Maire, Katia Ancelin, Eric Metzger, Roland Schüle, Evelyne Goillot, Frederic Relaix, Laurent Schaeffer
MyoD is a master regulator of myogenesis. Chromatin modifications required to trigger MyoD expression are still poorly described. Here, we demonstrate that the histone demethylase LSD1/KDM1a is recruited on the MyoD core enhancer upon muscle differentiation. Depletion of Lsd1 in myoblasts precludes the removal of H3K9 methylation and the recruitment of RNA polymerase II on the core enhancer, thereby preventing transcription of the non-coding enhancer RNA required for MyoD expression (CEeRNA). Consistently, Lsd1 conditional inactivation in muscle progenitor cells during embryogenesis prevented transcription of the CEeRNA and delayed MyoD expression...
February 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28228263/reciprocal-regulation-between-53bp1-and-the-anaphase-promoting-complex-cyclosome-is-required-for-genomic-stability-during-mitotic-stress
#8
Thomas J Kucharski, Paul E Minshall, Mohamed Moustafa-Kamal, Andrew S Turnell, Jose G Teodoro
The anaphase-promoting complex/cyclosome (APC/C) is an E3 ubiquitin ligase that targets substrates for degradation to promote mitotic progression. Here, we show that the DNA damage response protein 53BP1 contains conserved KEN boxes that are required for APC/C-dependent degradation in early mitosis. Mutation of the 53BP1 KEN boxes stabilized the protein and extended mitotic duration, whereas 53BP1 knockdown resulted in a shorter and delayed mitosis. Loss of 53BP1 increased APC/C activity, and we show that 53BP1 is a direct APC/C inhibitor...
February 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28228262/targeting-dna-damage-response-in-prostate-cancer-by-inhibiting-androgen-receptor-cdc6-atr-chk1-signaling
#9
Styliani Karanika, Theodoros Karantanos, Likun Li, Jianxiang Wang, Sanghee Park, Guang Yang, Xuemei Zuo, Jian H Song, Sankar N Maity, Ganiraju C Manyam, Bradley Broom, Ana M Aparicio, Gary E Gallick, Patricia Troncoso, Paul G Corn, Nora Navone, Wei Zhang, Shuhua Li, Timothy C Thompson
Cell division cycle 6 (CDC6), an androgen receptor (AR) target gene, is implicated in regulating DNA replication and checkpoint mechanisms. CDC6 expression is increased during prostate cancer (PCa) progression and positively correlates with AR in PCa tissues. AR or CDC6 knockdown, together with AZD7762, a Chk1/2 inhibitor, results in decreased TopBP1-ATR-Chk1 signaling and markedly increased ataxia-telangiectasia-mutated (ATM) phosphorylation, a biomarker of DNA damage, and synergistically increases treatment efficacy...
February 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28228261/context-dependent-effects-of-amplified-mapk-signaling-during-lung-adenocarcinoma-initiation-and-progression
#10
Michelle Cicchini, Elizabeth L Buza, Kyra M Sagal, A Andrea Gudiel, Amy C Durham, David M Feldser
Expression of oncogenic Kras(G12D) initiates lung adenomas in a mitogen-activated protein kinase (MAPK) signal-dependent manner from only a subset of cell types in the adult mouse lung. Amplification of MAPK signaling is associated with progression to malignant adenocarcinomas, but whether this is a cause or a consequence of disease progression is not known. To better understand the effects of MAPK signaling downstream of Kras(G12D) expression, we capitalized on the ability of Braf inhibition to selectively amplify MAPK pathway signaling in Kras(G12D)-expressing epithelial cells...
February 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28228260/chemotherapy-induced-ca-2-release-stimulates-breast-cancer-stem-cell-enrichment
#11
Haiquan Lu, Ivan Chen, Larissa A Shimoda, Youngrok Park, Chuanzhao Zhang, Linh Tran, Huimin Zhang, Gregg L Semenza
Breast cancer stem cells (BCSCs) play a critical role in tumor recurrence and metastasis. Exposure of breast cancer cells to chemotherapy leads to an enrichment of BCSCs. Here, we find that chemotherapy induces the expression of glutathione S-transferase omega 1 (GSTO1), which is dependent on hypoxia-inducible factor 1 (HIF-1) and HIF-2. Knockdown of GSTO1 expression abrogates carboplatin-induced BCSC enrichment, decreases tumor initiation and metastatic capacity, and delays tumor recurrence after chemotherapy...
February 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28228259/sirt1-regulates-dna-methylation-and-differentiation-potential-of-embryonic-stem-cells-by-antagonizing-dnmt3l
#12
Jinbeom Heo, Jisun Lim, Seungun Lee, Jaeho Jeong, Hyunsook Kang, YongHwan Kim, Jeong Wook Kang, Hwan Yeul Yu, Eui Man Jeong, Kyunggon Kim, Magda Kucia, Sabine J Waigel, Wolfgang Zacharias, Yinlu Chen, In-Gyu Kim, Mariusz Z Ratajczak, Dong-Myung Shin
Embryonic stem cell (ESC) abnormalities in genome methylation hamper the utility of their therapeutic derivatives; however, the underlying mechanisms are unknown. Here, we show that the nicotinamide adenine dinucleotide (NAD)-dependent deacetylase, Sirt1, selectively prevents abnormal DNA methylation of some developmental genes in murine ESCs by antagonizing Dnmt3l. Transcriptome and DNA methylome analyses demonstrated that Sirt1-null (Sirt1(-/-)) ESCs repress expression of a subset of imprinted and germline genes concomitant with increased DNA methylation of regulatory elements...
February 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28228258/clonal-expansion-of-lgr5-positive-cells-from-mammalian-cochlea-and-high-purity-generation-of-sensory-hair-cells
#13
Will J McLean, Xiaolei Yin, Lin Lu, Danielle R Lenz, Dalton McLean, Robert Langer, Jeffrey M Karp, Albert S B Edge
Death of cochlear hair cells, which do not regenerate, is a cause of hearing loss in a high percentage of the population. Currently, no approach exists to obtain large numbers of cochlear hair cells. Here, using a small-molecule approach, we show significant expansion (>2,000-fold) of cochlear supporting cells expressing and maintaining Lgr5, an epithelial stem cell marker, in response to stimulation of Wnt signaling by a GSK3β inhibitor and transcriptional activation by a histone deacetylase inhibitor...
February 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28228257/t-regulatory-cells-support-plasma-cell-populations-in-the-bone-marrow
#14
Arielle Glatman Zaretsky, Christoph Konradt, Fabien Dépis, James B Wing, Radhika Goenka, Daniela Gomez Atria, Jonathan S Silver, Sunglim Cho, Amaya I Wolf, William J Quinn, Julie B Engiles, Dorothy C Brown, Daniel Beiting, Jan Erikson, David Allman, Michael P Cancro, Shimon Sakaguchi, Li-Fan Lu, Christophe O Benoist, Christopher A Hunter
Long-lived plasma cells (PCs) in the bone marrow (BM) are a critical source of antibodies after infection or vaccination, but questions remain about the factors that control PCs. We found that systemic infection alters the BM, greatly reducing PCs and regulatory T (Treg) cells, a population that contributes to immune privilege in the BM. The use of intravital imaging revealed that BM Treg cells display a distinct behavior characterized by sustained co-localization with PCs and CD11c-YFP(+) cells. Gene expression profiling indicated that BM Treg cells express high levels of Treg effector molecules, and CTLA-4 deletion in these cells resulted in elevated PCs...
February 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28228256/first-breath-induced-type-2-pathways-shape-the-lung-immune-environment
#15
Simona Saluzzo, Anna-Dorothea Gorki, Batika M J Rana, Rui Martins, Seth Scanlon, Philipp Starkl, Karin Lakovits, Anastasiya Hladik, Ana Korosec, Omar Sharif, Joanna M Warszawska, Helen Jolin, Ildiko Mesteri, Andrew N J McKenzie, Sylvia Knapp
From birth onward, the lungs are exposed to the external environment and therefore harbor a complex immunological milieu to protect this organ from damage and infection. We investigated the homeostatic role of the epithelium-derived alarmin interleukin-33 (IL-33) in newborn mice and discovered the immediate upregulation of IL-33 from the first day of life, closely followed by a wave of IL-13-producing type 2 innate lymphoid cells (ILC2s), which coincided with the appearance of alveolar macrophages (AMs) and their early polarization to an IL-13-dependent anti-inflammatory M2 phenotype...
February 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28228255/can1-arginine-permease-deficiency-extends-yeast-replicative-lifespan-via-translational-activation-of-stress-response-genes
#16
Carine Beaupere, Brian M Wasko, Jared Lorusso, Brian K Kennedy, Matt Kaeberlein, Vyacheslav M Labunskyy
Transcriptional regulation plays an important role in the control of gene expression during aging. However, translation efficiency likely plays an equally important role in determining protein abundance, but it has been relatively understudied in this context. Here, we used RNA sequencing (RNA-seq) and ribosome profiling to investigate the role of translational regulation in lifespan extension by CAN1 gene deletion in yeast. Through comparison of the transcriptional and translational changes in cells lacking CAN1 with other long-lived mutants, we were able to identify critical regulatory factors, including transcription factors and mRNA-binding proteins, that coordinate transcriptional and translational responses...
February 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28228254/control-of-mitochondrial-remodeling-by-the-atpase-inhibitory-factor-1%C3%A2-unveils-a-pro-survival-relay-via-opa1
#17
Danilo Faccenda, Junji Nakamura, Giulia Gorini, Gurtej K Dhoot, Mauro Piacentini, Masusuke Yoshida, Michelangelo Campanella
The ubiquitously expressed ATPase inhibitory factor 1 (IF1) is a mitochondrial protein that blocks the reversal of the F1Fo-ATPsynthase, preventing dissipation of cellular ATP and ischemic damage. IF1 suppresses programmed cell death, enhancing tumor invasion and chemoresistance, and is expressed in various types of human cancers. In this study, we examined its effect on mitochondrial redox balance and apoptotic cristae remodeling, finding that, by maintaining ATP levels, IF1 reduces glutathione (GSH) consumption and inactivation of peroxiredoxin 3 (Prx3) during apoptosis...
February 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28228253/sirt6-suppresses-cancer-stem-like-capacity-in-tumors-with-pi3k-activation-independently-of-its-deacetylase-activity
#18
Rafael M Ioris, Mirco Galié, Giorgio Ramadori, Jason G Anderson, Anne Charollais, Georgia Konstantinidou, Xavier Brenachot, Ebru Aras, Algera Goga, Nicholas Ceglia, Carlos Sebastián, Denis Martinvalet, Raul Mostoslavsky, Pierre Baldi, Roberto Coppari
Cancer stem cells (CSCs) have high tumorigenic capacity. Here, we show that stem-like traits of specific human cancer cells are reduced by overexpression of the histone deacetylase sirtuin 6 (SIRT6). SIRT6-sensitive cancer cells bear mutations that activate phosphatidylinositol-3-kinase (PI3K) signaling, and overexpression of SIRT6 reduces growth, progression, and grade of breast cancer in a mouse model with PI3K activation. Tumor metabolomic and transcriptomic analyses reveal that SIRT6 overexpression dampens PI3K signaling and stem-like characteristics and causes metabolic rearrangements in this cancer model...
February 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28228252/complete-disruption-of-the-kainate-receptor-gene-family-results-in-corticostriatal-dysfunction-in-mice
#19
Jian Xu, John J Marshall, Herman B Fernandes, Toshihiro Nomura, Bryan A Copits, Daniele Procissi, Susumu Mori, Lei Wang, Yongling Zhu, Geoffrey T Swanson, Anis Contractor
Kainate receptors are members of the glutamate receptor family that regulate synaptic function in the brain. They modulate synaptic transmission and the excitability of neurons; however, their contributions to neural circuits that underlie behavior are unclear. To understand the net impact of kainate receptor signaling, we generated knockout mice in which all five kainate receptor subunits were ablated (5ko). These mice displayed compulsive and perseverative behaviors, including over-grooming, as well as motor problems, indicative of alterations in striatal circuits...
February 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/28228251/spatial-and-temporal-regulation-of-receptor-endocytosis-in-neuronal-dendrites-revealed-by-imaging-of-single-vesicle-formation
#20
Morgane Rosendale, Damien Jullié, Daniel Choquet, David Perrais
Endocytosis in neuronal dendrites is known to play a critical role in synaptic transmission and plasticity such as long-term depression (LTD). However, the inability to detect endocytosis directly in living neurons has hampered studies of its dynamics and regulation. Here, we visualized the formation of individual endocytic vesicles containing pHluorin-tagged receptors with high temporal resolution in the dendrites of cultured hippocampal neurons. We show that transferrin receptors (TfRs) are constitutively internalized at optically static clathrin-coated structures...
February 21, 2017: Cell Reports
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