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The role of the CNOT1 subunit of the CCR4-NOT complex in mRNA deadenylation and cell viability

Protein & Cell 2011年第9期2卷 755-763页

作者： Kentaro ito Akinori Takahashi ma.a.iro morita Toru Suzuki Tadashi Yamamoto Division of Oncology Department of Cancer BiologyInstitute of Medical ScienceUniversity of TokyoTokyo 108-8639Japan Cell Signal Unit Okinawa Institute of Science and Technology1919-1Okinawa 904-0412Japan

The human CCR4-NOT deadenylase complex consists of at least nine enzymatic and non-enzymatic *** evidence suggests that the non-enzymatic subunits are involved in the regulation of mRNA deadenylation,although their precise roles remain to be *** this study,we addressed the function of the CNOT1 subunit by depleting its expression in HeLa *** cytometric analysis revealed that the sub G1 fraction was increased in CNOT1-depleted ***,the same level of the sub G1 fraction was seen when cells were treated with a mixture of siRNAs targeted against all enzymatic subunits,suggesting that CNOT1 depletion induces apoptosis by destroying the CCR4-NOT-associated deadenylase *** analysis revealed that CNOT1 depletion leads to a reduction in the amount of other CCR4-NOT ***,the specific activity of the CNOT6L immunoprecipitates-associated deadenylase from CNOT1-depleted cells was less than that from control *** formation of P-bodies,where mRNA decay is reported to take place,was largely suppressed in CNOT1-depleted ***,CNOT1 has an important role in exhibiting enzymatic activity of the CCR4-NOT complex,and thus is critical in control of mRNA deadenylation and mRNA *** further showed that CNOT1 depletion enhanced CHOP mRNA levels and activated caspase-4,which is associated with endoplasmic reticulum ER stress-induced *** together,CNOT1 depletion structurally and functionally deteriorates the CCR4-NOTcomplex and induces stabilization of mRNAs,which results in the increment of translation causing ER stress-mediated *** conclude that CNOT1 contributes to cell viability by securing the activity of the CCR4-NOT deadenylase.

关键词： deadenylation CCR4-NOT small interfering RNA P-bodies apoptosis

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Protective effects of oral glutathione on fasting-induced intestinal atrophy through oxidative stress

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World Journal of Gastroenterology 2017年第36期23卷 6650-6664页

作者： Hiroyuki Uchida Yukari Nakajima Kazuo Ohtake Junta ito masahiko morita Ayako Kamimura Jun Kobayashi Division of Pathophysiology Department of Clinical Dietetics and Human NutritionFaculty of Pharmaceutical ScienceJosai University Kyowa Hakko Bio Co. Ltd.Healthcare Products Development Center

AIM To determine whether oral glutathione(GSH)administration can alleviate the effects of fasting-induced intestinal atrophy in the small intestinal mucosa. METHODS Rats were divided into eight *** group was fed ad libitum,another was fed ad libitum and received oral GSH,and six groups were administrated saline(SA)or GSH orally during *** height,apoptosis,and cell proliferation in the jejunum were histologically evaluated.i NOS protein expression(by immunohistochemistry),nitrite levels(by high performance liquid chromatography,as a measure of NO production),8-hydroxydeoxyguanosine formation(by ELISA,indicating ROS levels),glutathione/oxidized glutathione(GSH/GSSG)ratio(by enzymatic colorimetric detection),andγ-glutamyl transpeptidase(Ggt1)mR NA levels in the jejunum(by semi-quantitative RT-PCR)were also estimated. RESULTS O r a l G S H a d m i n i s t r a t i o n w a s d e m o n s t r a t e d t o drastically reduce fasting-induced intestinal atrophy in the *** particular,jejunal mucosal height was enhanced in GSH-treated animals compared to SA-treated animals[527.2±6.9 for 50 mg/kg GSH,567.6±5.4 for 500 mg/kg GSH vs 483.1±4.9(μm),Pmals compared to SA-treated animals for iN OS protein staining[0.337±0.016for 50 mg/kg GSH,0.317±0.017 for 500 mg/kg GSH vs 0.430±0.023(area of staining part/area of tissue),P<0.01 at 72 h]and NO[2.99±0.29 for 50 mg/kg GSH,2.88±0.19 for 500 mg/kg GSH vs 5.34±0.35(nmol/g tissue),P<0.01 at 72 h]and ROS[3.92±0.46for 50 mg/kg GSH,4.58±0.29 for 500 mg/kg GSH vs6.42±0.52(8-OHdG pg/μg DNA),P<0.01,P<0.05at 72 h,respectively]levels as apoptosis mediators in the ***,oral GSH administration attenuated cell proliferation decreases in the fasting jejunum[182.5±1.9 for 500 mg/kg GSH vs 155.8±3.4(5-Brd U positive cells/10 crypts),P<0.01 at 72h].Notably,both GSH concentration and Ggt1 m RNA expression in the jejunum were also attenu

关键词： Intestinal atrophy Glutathione Apoptosis Cell proliferation Inducible nitric oxide synthase

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Evolving concepts in bone infection: redefining “biofilm”,“acute vs. chronic osteomyelitis”, “the immune proteome” and “local antibiotic therapy”

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Bone Research 2019年第3期7卷 225-242页

作者： Elysia A. masters Ryan P. Trombetta Karen L. de Mesy Bentley Brendan F Boyce Ann Lindley Gill Steven R. Gill Kohei Nishitani ma.a.iro ishika.a.yugo morita.hiromu ito Sheila N. Bello-Irizarry mark Ninomiya James D. Brodell Jr. Charles C. Lee Stephanie P. Hao Irvin Oh Chao Xie Hani A. Awad John L. Daiss John R. Owen Stephen L. Kates Edward M. Schwarz Gowrishankar Muthukrishnan Center for Musculoskeletal Research University of Rochester Medical Center Rochester NY USA Department of Biomedical Engineering University of Rochester Medical Center Rochester NY USA Department of Pathology and Laboratory Medicine University of Rochester Medical Center Rochester NY USA Department of Orthopaedics University of Rochester Medical Center Rochester NY USA Department of Microbiology & Immunology University of Rochester Medical Center Rochester NY USA Department of Orthopaedic Surgery Kyoto University Kyoto Japan Department of Orthopaedic Surgery Virginia Commonwealth University Medical Center Richmond VA USA

Osteomyelitis is a devastating disease caused by microbial infection of bone. While the frequency of infection following elective orthopedic surgery is low, rates of reinfection are disturbingly high. Staphylococcus aureus is responsible for the majority of chronic osteomyelitis cases and is often considered to be incurable due to bacterial persistence deep within bone. Unfortunately, there is no consensus on clinical classifications of osteomyelitis and the ensuing treatment algorithm. Given the high patient morbidity,mortality, and economic burden caused by osteomyelitis, it is important to elucidate mechanisms of bone infection to inform novel strategies for prevention and curative treatment. Recent discoveries in this field have identified three distinct reservoirs of bacterial biofilm including: Staphylococcal abscess communities in the local soft tissue and bone marrow, glycocalyx formation on implant hardware and necrotic tissue, and colonization of the osteocyte-lacuno canalicular network(OLCN) of cortical bone. In contrast, *** intracellular persistence in bone cells has not been substantiated in vivo, which challenges this mode of chronic osteomyelitis. There have also been major advances in our understanding of the immune proteome against S. aureus, from clinical studies of serum antibodies and media enriched for newly synthesized antibodies(MENSA), which may provide new opportunities for osteomyelitis diagnosis, prognosis, and vaccine development. Finally, novel therapies such as antimicrobial implant coatings and antibiotic impregnated 3D-printed scaffolds represent promising strategies for preventing and managing this devastating disease. Here, we review these recent advances and highlight translational opportunities towards a cure.

关键词： disease caused by soft tissue necrotic tissuel

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Systemic IL-27 administration prevents abscess formation and osteolysis via local neutrophil recruitment and activation

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Bone Research 2022年第4期10卷 826-837页

作者： yugo morita Motoo Saito Javier Rangel-Moreno Anthony M.Franchini John R.Owen John C.martinez John L.Daiss Karen L.de Mesy Bentley Stephen L.Kates Edward M.Schwarz Gowrishankar Muthukrishnan Center for Musculoskeletal Research University of Rochester Medical CenterRochesterNYUSA Division of Allergy Immunology and RheumatologyDepartment of MedicineUniversity of Rochester Medical CenterRochesterNYUSA Department of Environmental Medicine University of Rochester School of Medicine and DentistryRochesterNYUSA Department of Orthopedic Surgery Virginia Commonwealth UniversityRichmondVAUSA Department of Orthopedics University of Rochester Medical CenterRochesterNYUSA Department of Pathology and Laboratory Medicine University of Rochester Medical CenterRochesterNYUSA

Interleukin-27 is a pleiotropic cytokine whose functions during bacterial infections remain controversial,and its role in patients with *** osteomyelitis is *** address this knowledge gap,we completed a clinical study and observed elevated serum IL-27 levels(20-fold higher,Pmacrophages and osteoblasts but not by ***,exogenous IL-27p28(~2 ng·mL^(−1) in serum)delivery ameliorated soft tissue abscesses and periimplant bone loss during infection,accompanied by enhanced local IL-27 expression,significant accumulation of RORγt^(+)neutrophils at the infection site,a decrease in RANK^(+) cells,and compromised osteoclast *** effects were not observed in IL-27Rα^(−/−)mice compared with WT mice,suggesting that IL-27 is dispensable for immunity but mediates redundant immune and bone cell functions during *** vitro studies and bulk RNA-seq of infected tibiae showed that IL-27 increased nos1,nos2,il17α,il17f,and rorc expression but did not directly stimulate ***,these results identify a novel phenomenon of IL-27 expression by osteoblasts immediately following *** infection of bone and suggest a protective role of systemic IL-27 in osteomyelitis.

关键词： abscess protective immunity

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Development of Functional Interlaminar Pathways in the Mouse Superior Colliculus Revealed by Optical Imaging with Axonal Labeling

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Journal of Biosciences and Medicines 2017年第8期5卷 11-35页

作者： Nana morita Tetsufumi ito Ryohei P. Hasegawa Kazuyuki Murase Graduate School of Engineering University of Fukui Fukui Japan Anatomy II School of Medicine Kanazawa Medical University Ishikawa Japan Human Technology Research Institute National Institute of Advanced Industrial Science and Technology (AIST) Ibaraki Japan Organization for Life Science Advancement Programs University of Fukui Fukui Japan

The superior colliculus (SC) is a laminated midbrain structure responsible for visual orientation behaviors. In the mature SC, neurons in the stratum griseum superficiale (SGS) receive visual inputs that contribute to exciting premotor neurons in the stratum griseum intermediale (SGI) through a dorsoventral pathway. SGI activation generates feedback signals to the SGS through a ventrodorsal pathway. However, the developmental changes in signal transmission within the SC around the time of eye opening are not yet well understood. We compared the functional connections between the SGS and SGI before and after eye opening by imaging the neuronal population responses using a voltage-sensitive absorption dye in mouse SC slices. Electrophoresis of a fluorescent dye from the stimulating electrodes was used to fill the cells in the stimulated site. We here show that the dorsoventral transmission is present both before and after eye opening. This is in contrast to our previous finding that the ventrodorsal transmission develops after eye opening. Functions of intrinsic inhibitory systems mediated by gamma-aminobutyric acid were also investigated with the antagonist. The processes stained by electrophoresis from stimulating electrodes before eye opening were confined within the respective stimulated layers. Whereas, after eye opening, the processes were widely extended especially dorsoventrally and ventrodorsally invading the SGI and SGS, respectively. These corresponded well to the early component of voltage responses that is known to reflect the activation of presynaptic elements, presumably the axonal arborizations and varicosities. Thus, the optically-revealed functional connections between the SGS and SGI were correlated to the morphology.

关键词： Axonal Projection Optical Imaging Superior Colliculus Visual Orientation Voltage-Sensitive Dye

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Contribution of the Large Helical Device Plasmas to Alfvén Eigenmode Physics in Toroidal Plasmas

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Plasma Science and Technology 2009年第4期11卷 377-380页

作者： K. TOI M. ISOBE M. OSAKABE F. WATANABE K. OGAWA T. TOKUZAWA A. SHIMIZU T. IDO K. IDA, T. ito S. morita K. NAGAOKA K. NARIHARA M. NISHIURA S. OHDACHI S. SAKAKIBARA K. TANAKA LHD Experiment Group National Institute for Fusion Science Toki 509-5292 Japan Department of Energy Engineering and Science Nagoya University Nagoya 464-8601 Japan

In the large helical device （LHD） having three dimensional configuration, Alfven eigenmodes （AEs） destabilized by energetic ions are widely investigated using neutral beam heated plasmas with monotonic and non-monotonic rotational transform （l/2π） profiles. In a plasma with monotonic l/2π-profile, core-localized toroidicity-induced Alfven eigenmode （TAE） as well as global one are often observed. With the increase in the averaged toroidal beta value, defined as the ratio of total plasma pressure to toroidal magnetic pressure, core-localized TAE with low toroidal mode number becomes global. In a relatively high beta plasma with monotonic l/2π-profile, two TAEs with different toroidal mode number often interact nonlinearly and generate another modes through three wave coupling. In a plasma with non-monotonic l/2π-profile generated by intense counter neutral beam current drive, reversed shear Alfven eigenmode （RSAE） and geodesic acoustic mode （CAM） excited by energetic ions were observed for the first time in a helical plasma. Nonlinear coupling was also observed between RSAE and GAM.

关键词： alpha particles Alfven eigenmodes geodesic acoustic mode helical/stellarator

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Recent Advances in Japanese Fisheries Science in the Kuroshio-Oyashio Region through Development of the FRA-ROMS Ocean Forecast System: Overview of the Reproducibility of Reanalysis Products

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Open Journal of marine Science 2017年第1期7卷 62-90页

作者： Hiroshi Kuroda Takashi Setou Shigeho Kakehi Shin-ichi ito Takeshi Taneda Tomonori Azumaya Denzo Inagake Yutaka Hiroe Kenji Morinaga makoto Okazaki Takashi Yokota Takeshi Okunishi Kazuhiro Aoki yugo Shimizu Daisuke Hasegawa Tomowo Watanabe Hokkaido National Fisheries Research Institute Japan Fisheries Research and Education Agency Kushiro Japan National Research Institute of Fisheries Science Japan Fisheries Research and Education Agency Yokohama Japan Tohoku National Fisheries Research Institute Japan Fisheries Research and Education Agency Shiogama Japan Atmosphere and Ocean Research Institute University of Tokyo Kashiwa Japan Seikai National Fisheries Research Institute Japan Fisheries Research and Education Agency Nagasaki Japan National Research Institute of Far Seas Fisheries Japan Fisheries Research and Education Agency Yokohama Japan Hokkaido National Fisheries Research Institute Japan Fisheries Research and Education Agency Akkeshi Japan Headquaters Japan Fisheries Research and Education Agency Yokohama Japan

To address various fisheries science problems around Japan, the Japan Fisheries Research and Education Agency (FRA) has developed an ocean forecast system by combining an ocean circulation model based on the Regional Ocean Modeling System (ROMS) with three-dimensional variational analysis schemes. This system, which is called FRA-ROMS, is a basic and essential tool for the systematic conduct of fisheries science. The main aim of FRA-ROMS is to realistically simulate mesoscale variations over the Kuroshio-Oyashio region. Here, in situ oceanographic and satellite data were assimilated into FRA-ROMS using a weekly time window. We first examined the reproducibility through comparison with several oceanographic datasets with an Eulerian reference frame. FRA-ROMS was able to reproduce representative features of mesoscale variations such as the position of the Kuroshio path, variability of the Kuroshio Extension, and southward intrusions of the Oyashio. Second, using a Lagrangian reference frame, we estimated position errors between ocean drifters and particles passively transported by simulated currents, because particle tracking is an essential technique used in applications of reanalysis products to fisheries science. Finally, we summarize recent and ongoing fisheries studies that use FRA-ROMS and mention several new developments and enhancements that will be implemented in the near future.

关键词： ROMS 3D-Var Objective Analysis Reanalysis Data Fisheries Science Particle-Tracking Experiment

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