374 results on '"Kentaro Ito"'
Search Results
352. A single crossing-over event in voltage-sensitive Na+ channel genes may cause critical failure of dengue mosquito control by insecticides.
- Author
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Koichi Hirata, Osamu Komagata, Kentaro Itokawa, Atsushi Yamamoto, Takashi Tomita, and Shinji Kasai
- Subjects
Arctic medicine. Tropical medicine ,RC955-962 ,Public aspects of medicine ,RA1-1270 - Abstract
The voltage-sensitive sodium (Na+) channel (Vssc) is the target site of pyrethroid insecticides. Pest insects develop resistance to this class of insecticide by acquisition of one or multiple amino acid substitution(s) in this channel. In Southeast Asia, two major Vssc types confer pyrethroid resistance in the dengue mosquito vector Aedes aegypti, namely, S989P+V1016G and F1534C. We expressed several types of Vssc in Xenopus oocytes and examined the effect of amino acid substitutions in Vssc on pyrethroid susceptibilities. S989P+V1016G and F1534C haplotypes reduced the channel sensitivity to permethrin by 100- and 25-fold, respectively, while S989P+V1016G+F1534C triple mutations reduced the channel sensitivity to permethrin by 1100-fold. S989P+V1016G and F1534C haplotypes reduced the channel sensitivity to deltamethrin by 10- and 1-fold (no reduction), respectively, but S989P+V1016G+F1534C triple mutations reduced the channel sensitivity to deltamethrin by 90-fold. These results imply that pyrethroid insecticides are highly likely to lose their effectiveness against A. aegypti if such a Vssc haplotype emerges as the result of a single crossing-over event; thus, this may cause failure to control this key mosquito vector. Here, we strongly emphasize the importance of monitoring the occurrence of triple mutations in Vssc in the field population of A. aegypti.
- Published
- 2014
- Full Text
- View/download PDF
353. Mechanisms of pyrethroid resistance in the dengue mosquito vector, Aedes aegypti: target site insensitivity, penetration, and metabolism.
- Author
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Shinji Kasai, Osamu Komagata, Kentaro Itokawa, Toshio Shono, Lee Ching Ng, Mutsuo Kobayashi, and Takashi Tomita
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Arctic medicine. Tropical medicine ,RC955-962 ,Public aspects of medicine ,RA1-1270 - Abstract
Aedes aegypti is the major vector of yellow and dengue fevers. After 10 generations of adult selection, an A. aegypti strain (SP) developed 1650-fold resistance to permethrin, which is one of the most widely used pyrethroid insecticides for mosquito control. SP larvae also developed 8790-fold resistance following selection of the adults. Prior to the selections, the frequencies of V1016G and F1534C mutations in domains II and III, respectively, of voltage-sensitive sodium channel (Vssc, the target site of pyrethroid insecticide) were 0.44 and 0.56, respectively. In contrast, only G1016 alleles were present after two permethrin selections, indicating that G1016 can more contribute to the insensitivity of Vssc than C1534. In vivo metabolism studies showed that the SP strain excreted permethrin metabolites more rapidly than a susceptible SMK strain. Pretreatment with piperonyl butoxide caused strong inhibition of excretion of permethrin metabolites, suggesting that cytochrome P450 monooxygenases (P450s) play an important role in resistance development. In vitro metabolism studies also indicated an association of P450s with resistance. Microarray analysis showed that multiple P450 genes were over expressed during the larval and adult stages in the SP strain. Following quantitative real time PCR, we focused on two P450 isoforms, CYP9M6 and CYP6BB2. Transcription levels of these P450s were well correlated with the rate of permethrin excretion and they were certainly capable of detoxifying permethrin to 4'-HO-permethrin. Over expression of CYP9M6 was partially due to gene amplification. There was no significant difference in the rate of permethrin reduction from cuticle between SP and SMK strains.
- Published
- 2014
- Full Text
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354. A Ferroelectric Field Effect Device Using Thin Film SnO2and Gate Insulator BaTiO3
- Author
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Kentaro Ito and Hidetoshi Tsuchiya
- Subjects
Materials science ,Physics and Astronomy (miscellaneous) ,Solid-state physics ,business.industry ,General Engineering ,General Physics and Astronomy ,Field effect ,Insulator (electricity) ,Semiconductor device ,Dielectric ,Ferroelectricity ,Optoelectronics ,Field-effect transistor ,Thin film ,business - Published
- 1975
355. High efficiency indium oxide/cadmium telluride solar cells
- Author
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T. Nakazawa, K. Takamizawa, and Kentaro Ito
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Materials science ,Physics and Astronomy (miscellaneous) ,business.industry ,Energy conversion efficiency ,Solar energy ,Copper indium gallium selenide solar cells ,Polymer solar cell ,Cadmium telluride photovoltaics ,law.invention ,Optics ,law ,Solar cell ,Optoelectronics ,Thin film ,Homojunction ,business - Abstract
Solar cells have been fabricated by reactive deposition of thin‐film n‐In2O3 onto single‐crystal p‐CdTe. The cell has a total area solar power conversion efficiency of 13.4% which corresponds to an active area efficiency of 14.4% at air mass 1.5 without antireflection coatings. The cell consists of a buried homojunction structure with low dark saturation current density.
- Published
- 1987
356. Photovoltaic Effect atnCdS-pInP Heterojunctions
- Author
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Toshimasa Ohsawa and Kentaro Ito
- Subjects
Materials science ,Physics and Astronomy (miscellaneous) ,business.industry ,General Engineering ,General Physics and Astronomy ,Optoelectronics ,Heterojunction ,Photovoltaic effect ,business - Published
- 1975
357. Two auxiliary factors promote Dmc1-driven DNA strand exchange via stepwise mechanisms.
- Author
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Hideo Tsubouchi, Bilge Argunhan, Kentaro Ito, Masayuki Takahashi, and Hiroshi Iwasaki
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GERM cells , *DNA , *SOMATIC cells , *EXCHANGE - Abstract
Homologous recombination (HR) is a universal mechanism operating in somatic and germ-line cells, where it contributes to the maintenance of genome stability and ensures the faithful distribution of genetic material, respectively. The ability to identify and exchange the strands of two homologous DNA molecules lies at the heart of HR and is mediated by RecA-family recombinases. Dmc1 is a meiosis-specific RecA homolog in eukaryotes, playing a predominant role in meiotic HR. However, Dmc1 cannot function without its two major auxiliary factor complexes, Swi5-Sfr1 and Hop2-Mnd1. Through biochemical reconstitutions, we demonstrate that Swi5-Sfr1 and Hop2-Mnd1 make unique contributions to stimulate Dmc1-driven strand exchange in a synergistic manner. Mechanistically, Swi5-Sfr1 promotes establishment of the Dmc1 nucleoprotein filament, whereas Hop2-Mnd1 defines a critical, rate-limiting step in initiating strand exchange. Following execution of this function, we propose that Swi5-Sfr1 then promotes strand exchange with Hop2-Mnd1. Thus, our findings elucidate distinct yet complementary roles of two auxiliary factors in Dmc1-driven strand exchange, providing mechanistic insights into some of the most critical steps in meiotic HR. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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358. Planar-Type Gunn Diode of InP
- Author
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Kentaro Ito, Yoshio Nakamura, Akio Dohi, Akinori Shibayama, Tadahiro Ohmi, and Kimio Murayama
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Physics ,Planar ,Optics ,Physics and Astronomy (miscellaneous) ,Condensed matter physics ,business.industry ,General Engineering ,General Physics and Astronomy ,business ,Gunn diode - Abstract
Wrong Kimio Murayama, Yoshio Nakamura, Akinori Shibayama, Akio Dohi, Tadahiro Ohmi and Kentaro Ito Department of Electronics, Tokyo Institute of Technology, Meguro-ku, Tokyo Correct Kimio Murayama, Yoshio Nakamura, Akinori Shibayama, Akio Dohi, Tadahiro Ohmi and Kentaro Ito1 Department of Electronics, Tokyo Institute of Technology, Meguro-ku, Tokyo1Department of Electronics, Shinsyu University, Nagano The present address with five stars in the foot note on the page 662 should be erased. L. 14 from the bottom, Left on p. 665 Wrong Equation (1).... Correct Equation (2)....
- Published
- 1974
359. Transparent and Conductive Cadmium-Tin Oxide Films Deposited by Atom Beam Sputtering
- Author
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Kentaro Ito and Tatsuo Nakazawa
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Materials science ,business.industry ,General Engineering ,Oxide ,General Physics and Astronomy ,Mineralogy ,Heterojunction ,Tin oxide ,Amorphous solid ,chemistry.chemical_compound ,chemistry ,Sputtering ,Optoelectronics ,Thin film ,business ,Layer (electronics) ,Transparent conducting film - Abstract
Transparent and conductive cadmium-tin oxide films with resistivities of 9×10-4 Ω cm and transmittance higher than 80% over the visible range were prepared by atom beam sputtering. The structure of the deposited film was amorphous and its composition was highly deficient in CdO compared with Cd2SnO4. This CTO film was used as the window layer of a heterojunction solar cell.
- Published
- 1988
360. Transparent and Highly Conductive Films of ZnO Prepared by RF Sputtering
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Kentaro Ito and Tatsuo Nakazawa
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Argon ,Materials science ,business.industry ,General Engineering ,General Physics and Astronomy ,chemistry.chemical_element ,Zinc ,Microstructure ,Crystal ,Optics ,chemistry ,Sputtering ,Electrical resistivity and conductivity ,X-ray crystallography ,Optoelectronics ,Thin film ,business - Abstract
Zinc oxide thin films with the resistivity of 5×10-3Ω·cm and the transparency of above 80% at the wavelength between 400 and 800 nm have been prepared by conventional rf sputtering in pure argon from a zinc oxide target. A close relation of their electrical characteristics with crystallographic characteristics is found using X-ray diffraction analysis. The low resistivity films consist of very small crystal grains, the c-axis of which is not preferentially oriented or is weakly oriented parallel to the substrate surface.
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- 1983
361. Photovoltaic Effect in Monoclinic ZnP2
- Author
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Yoshihiro Matsuura, Hidemi Takenouchi, Tatsuo Nakazawa, and Kentaro Ito
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Materials science ,Absorption spectroscopy ,business.industry ,General Engineering ,General Physics and Astronomy ,Photovoltaic effect ,Dichroism ,Molecular physics ,Wavelength ,Spectral sensitivity ,Optoelectronics ,business ,Single crystal ,Monoclinic crystal system ,Diode - Abstract
Heterojunction diodes consisting of n type In2O3 film and p type monoclinic ZnP2 single crystal were formed. Spectral response of monoclinic ZnP2 was measured on these diodes using polarized monochromatic light. At wavelengths around 0.76 µm, the response for the electric vector of plane polarized light parallel to the c-axis was considerably larger than that for the light polarized perpendicular to c. The anisotropy of the response corresponds to an intense dichroism observed in the absorption spectrum of monoclinic ZnP2. The overall response observed within the 0.35-0.86 µm range matches with the solar spectrum.
- Published
- 1981
362. Solution-Grown Silicon Solar Cells
- Author
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Kentaro Ito and Kunio Kojima
- Subjects
Theory of solar cells ,Materials science ,integumentary system ,Silicon ,business.industry ,technology, industry, and agriculture ,General Engineering ,General Physics and Astronomy ,chemistry.chemical_element ,Hybrid solar cell ,Quantum dot solar cell ,Copper indium gallium selenide solar cells ,Polymer solar cell ,Monocrystalline silicon ,chemistry ,Optoelectronics ,Plasmonic solar cell ,business - Abstract
Silicon pn junction solar cells with the conversion efficiency up to 9.0% were prepared by a liquid phase epitaxial technique in which aluminum was used as a solvent. The estimated surface recombination velocity of the solar cells was one or two orders of magnitude less than that of the conventional silicon solar cells. The fabrication method proposed in this paper is a low temperature process inherently and provides the cells free from the so-called “dead region.”
- Published
- 1980
363. Hydrogen Detector Utilizing Metal-Semiconductor Contacts
- Author
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Kentaro Ito
- Subjects
Materials science ,Hydrogen ,business.industry ,Detector ,General Engineering ,Analytical chemistry ,Oxide ,PIN diode ,General Physics and Astronomy ,chemistry.chemical_element ,Schottky diode ,law.invention ,chemistry.chemical_compound ,Semiconductor ,chemistry ,law ,Optoelectronics ,business ,Step recovery diode ,Diode - Abstract
A hydrogen detector was developed in which the hydrogen-sensitive palladium/oxide/semiconductor (Pd MOS) Schottky diode and the reference diode were connected in series with each other. The latter diode was made by deposition of a thin gold film on the other Pd MOS structure. The effects by temperature variation and ageing were so compensated that several thousand ppm H2 can be stably detected in the atmosphere ambient. A method of hydrogen detection was proposed where the photovoltaic output of the diode was monitored.
- Published
- 1981
364. Electrical and Optical Properties of Stannite-Type Quaternary Semiconductor Thin Films
- Author
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Kentaro Ito and Tatsuo Nakazawa
- Subjects
Band gap ,business.industry ,Inorganic chemistry ,General Engineering ,General Physics and Astronomy ,Substrate (electronics) ,Stannite ,engineering.material ,chemistry.chemical_compound ,Semiconductor ,chemistry ,Sputtering ,engineering ,Optoelectronics ,CZTS ,Kesterite ,Thin film ,business - Abstract
Quaternary stannite-type semiconductor films of Cu2CdSnS4 and Cu2ZnSnS4 with (112) orientation were deposited on heated glass substrates using atom beam sputtering. These p-type films showed resistivities which were decreasing functions of the substrate temperature up to 240°C. The films had an absorption coefficient larger than 1 × 104 cm-1 in the visible wavelength range. The direct optical band gaps of the (112) oriented polycrystalline films were estimated as 1.06 eV and 1.45 eV for Cu2CdSnS4 and Cu2ZnSnS4, respectively.
- Published
- 1988
365. Silicon Solar Cells Made by Liquid Phase Epitaxy
- Author
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Akira Masamura, Kentaro Ito, and Tatsuo Nakazawa
- Subjects
Materials science ,Silicon ,business.industry ,General Engineering ,General Physics and Astronomy ,chemistry.chemical_element ,Quantum dot solar cell ,Epitaxy ,complex mixtures ,Copper indium gallium selenide solar cells ,Polymer solar cell ,law.invention ,Monocrystalline silicon ,chemistry ,law ,Solar cell ,Optoelectronics ,business ,p–n junction - Abstract
Silicon pn junction solar cells with the conversion efficiency up to 10.4% were made by a liquid phase epitaxial technique. Using gallium instead of aluminum as a solvent, p type silicon epitaxial layers with more uniform thickness were obtained on the n type silicon substrates at lower deposition temperatures. It was found that the fill factor of this solar cell was limited by the series resistance of the diode. The cell efficiency can be increased up to 14% without antireflection coatings by reducing the series resistance effect.
- Published
- 1982
366. Epitaxial Growth of Ge Layers on Si Substrates by Vacuum Evaporation
- Author
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Kiyoshi Takahashi and Kentaro Ito
- Subjects
Materials science ,business.industry ,Ultra-high vacuum ,General Engineering ,General Physics and Astronomy ,Heterojunction ,Epitaxy ,Vacuum evaporation ,Crystallography ,Optoelectronics ,Dislocation ,business ,Single crystal ,Diode - Abstract
The initial growth of vacuum-deposited Ge films on Si (111) has been studied. It has been shown that single crystal Ge layers can be obtained on cleaned Si substrates in high vacuum, but that misfit dislocations exist at the interface of Ge and Si. Electrical properties of p Ge- n Si heterojunctions made by vacuum evaporation have been studied. The I-V characteristics of the diodes can be explained through the existence of misfit dislocation.
- Published
- 1968
367. Response to various periods of mechanical stimuli in Physarum plasmodium.
- Author
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Takuya Umedachi, Kentaro Ito, Ryo Kobayashi, Akio Ishiguro, and Toshiyuki Nakagaki
- Subjects
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PHYSARUM , *CELLULAR mechanics , *MOLECULAR biology - Abstract
Response to mechanical stimuli is a fundamental and critical ability for living cells to survive in hazardous conditions or to form adaptive and functional structures against force(s) from the environment. Although this ability has been extensively studied by molecular biology strategies, it is also important to investigate the ability from the viewpoint of biological rhythm phenomena so as to reveal the mechanisms that underlie these phenomena. Here, we use the plasmodium of the true slime mold Physarum polycephalum as the experimental system for investigating this ability. The plasmodium was repetitively stretched for various periods during which its locomotion speed was observed. Since the plasmodium has inherent oscillation cycles of protoplasmic streaming and thickness variation, how the plasmodium responds to various periods of external stretching stimuli can shed light on the other biological rhythm phenomena. The experimental results show that the plasmodium exhibits response to periodic mechanical stimulation and changes its locomotion speed depending on the period of the stretching stimuli. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
368. Smart watch-based coaching with tiotropium and olodaterol ameliorates physical activity in patients with chronic obstructive pulmonary disease.
- Author
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OSAMU HATAJI, YOICHI NISHII, KENTARO ITO, TADASHI SAKAGUCHI, HARUKO SAIKI, YUTA SUZUKI, D'ALESSANDRO-GABAZZA, CORINA, HAJIME FUJIMOTO, TETSU KOBAYASHI, GABAZZA, ESTEBAN C., and OSAMU TAGUCHI
- Subjects
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OBSTRUCTIVE lung diseases patients , *PULMONARY function tests , *QUALITY of life , *PLACEBOS , *PHYSICAL activity - Abstract
Combined therapy with tiotropium and olodaterol notably improves parameters of lung function and quality of life in patients with chronic obstructive pulmonary disease (COPD) compared to mono-components; however, its effect on physical activity is unknown. The present study evaluated whether combination therapy affects daily physical performance in patients with COPD under a smart watch-based encouragement program. This was a non-blinded clinical trial with no randomization or placebo control. A total of 20 patients with COPD were enrolled in the present study. The patients carried an accelerometer for 4 weeks; they received no therapy during the first 2 weeks but they were treated with combined tiotropium and olodaterol under a smart watch-based encouragement program for the last 2 weeks. The pulmonary function test, COPD assessment test, 6-min walk distance and parameters of physical activity were significantly improved (P<0.05) by combination therapy under smart watch-based coaching compared with values prior to treatment. To the best of our knowledge, the present study for the first time provides evidence that smart watch-based coaching in combination with tiotropium and olodaterol may improve daily physical activity in chronic obstructive pulmonary disease. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
369. CuIn(SxSe1-x)2Thin Films by Sulfurization
- Author
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Tsuyoshi Ohashi, Tsuyoshi Ohashi, Arnulf Jä, Arnulf Jä, Tsutomu Miyazawa, Tsutomu Miyazawa, Yoshio Hashimoto, Yoshio Hashimoto, and Kentaro Ito, Kentaro Ito
- Abstract
Polycrystalline films of the quaternary alloy CuIn(SxSe1-x)2with a thickness of 1 to 3 µm have been synthesized by sulfurization of InSe/Cu precursors. The films have been characterized with respect to their composition and their optical and their electronic properties. X-ray diffraction measurements of the CuIn(SxSe1-x)2alloy films showed a shift of their (112) diffraction peaks corresponding to the S/(S+Se) composition ratio between 0.5 and 0.9. The optical transmission measurements revealed that the band gap of the alloy films shifts from 1.24 to 1.48 eV with increase of the composition ratio. All CuIn(SxSe1-x)2alloy films prepared by this method exhibited p-type conduction which was determined using a thermoprobe. Electrical transport properties were assessed by Hall measurements in the van der Pauw geometry.
- Published
- 1995
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370. In2O3/CdS/CuInS2Thin-Film Solar Cell with 9.7% Efficiency
- Author
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Ogawa, Yoshitaka, Jäger-Waldau, Arnulf, Yoshio Hashimoto, Yoshio Hashimoto, and Kentaro Ito, Kentaro Ito
- Abstract
An efficient thin-film photovoltaic cell has been fabricated using the heterostructure consisting of a CuInS2film obtained by sulfurization of a metallic precursor, a chemical-bath-deposited CdS layer, and an atom-beam-sputtered In2O3film. A preceding KCN treatment of the Cu-rich CuInS2film lowered the Cu/In ratio and raised the resistivity. A cell conversion efficiency of 9.7% (active area efficiency>10%) at air mass 1.5 has been achieved without antireflection coatings.
- Published
- 1994
- Full Text
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371. Atypical Splenic Abscesses Due to Clostridioides difficile.
- Author
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Yukiko Komeno, Takeru Iida, Ayumu Kocha, Naohiro Kadoma, Kentaro Ito, Masaaki Morito, Makoto Kodama, Keiko Abe, Masayoshi Ijichi, and Tomiko Ryu
- Subjects
- *
CLOSTRIDIOIDES difficile , *BLUNT trauma , *ABSCESSES , *MAGNETIC resonance imaging , *ENTEROCOCCAL infections , *ENTEROCOCCUS faecium , *BACTEROIDES fragilis - Abstract
Patient: Male, 90-year-old Final Diagnosis: Clostridioides difficile splenic abscesses Symptoms: Abdominal pain * fever * weight loss Medication: -- Clinical Procedure: Antibiotics * splenectomy Specialty: Infectious Diseases Objective: Rare disease Background: Splenic abscess is a rare infectious disease that occurs after bloodstream infection and trauma. It has become more common due to an increase in the number of immunocompromised patients. They typically present with round cystic lesions demonstrated by ultrasonography, computed tomography (CT), and magnetic resonance imaging (MRI). Clostridioides difficile (formerly Clostridium difficile) is a well-known cause of pseudomembranous colitis, but extraintestinal manifestations are very rare. To the best of our knowledge, only 9 cases of splenic abscess due to C. difficile have been reported in the literature. Case Report: A 90-year-old man presented with weight loss, fever, and abdominal pain. Contrast-enhanced CT revealed splenomegaly with irregular hypodense nodules. Image-guided biopsy or drainage was not performed for a technical reason. MRI showed atypical nodules with mixed high and low signals on both T1- and T2-weighted images, which were inconclusive. A laparoscopic splenectomy was performed, which resulted in partial removal due to severe adhesion of the spleen to the surrounding tissues. Cultures of splenic pus yielded C. difficile, Enterococcus faecium, and Bacteroides fragilis. Pathological examination of the spleen showed widespread abscesses with hemorrhage and necrosis, leading to the diagnosis of splenic abscesses. Intravenous administration of vancomycin, clindamycin or metronidazole was ineffective. He died of fatal arrhythmia 5 months after the initial diagnosis of splenic abscess. Conclusions: Splenic abscess can present with atypical imaging findings owing to chronic inflammation, bleeding, and necrosis. Although polymicrobial, this is the tenth reported case of splenic abscess caused by C. difficile. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
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372. Magnetic and calorimetric studies on rare-earth iron borates LnFe3(BO3)4 (Ln=Y, La–Nd, Sm–Ho).
- Author
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Yukio Hinatsu, Yoshihiro Doi, Kentaro Ito, Makoto Wakeshima, and Alemi, Abdolali
- Subjects
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BORATES , *IRON compounds , *MOSSBAUER spectroscopy - Abstract
A series of rare-earth iron borates having general formula LnFe3(BO3)4 (Ln=Y, La–Nd, Sm–Ho) were prepared and their magnetic properties have been investigated by the magnetic susceptibility, specific heat, and 57Fe Mössbauer spectrum measurements. These borates show antiferromagnetic transitions at low temperatures and their magnetic transition temperatures increase with decreasing Ln3+ ionic radius from 22K for LaFe3(BO3)4 to 40K for TbFe3(BO3)4. In addition, X-ray diffraction, specific heat, and differential thermal analysis (DTA) measurements indicate that the phase transition occurs for the LnFe3(BO3)4 compounds with Ln=Eu–Ho, Y, and its transition temperature increases remarkably with decreasing Ln3+ ionic radius from 88K for Ln=Eu to 445K for Ln=Y. [Copyright &y& Elsevier]
- Published
- 2003
- Full Text
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373. A conserved Ctp1/CtIP C-terminal peptide stimulates Mre11 endonuclease activity.
- Author
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Zdravković, Aleksandar, Daley, James M., Dutta, Arijit, Tatsuya Niwa, Yasuto Murayama, Shuji Kanamaru, Kentaro Ito, Takahisa Maki, Argunhan, Bilge, Masayuki Takahashi, Hideo Tsubouchi, Sung, Patrick, and Hiroshi Iwasaki
- Subjects
- *
DOUBLE-strand DNA breaks , *DNA repair , *SCHIZOSACCHAROMYCES pombe , *PHOSPHORYLATION , *AMINO acids - Abstract
The Mre11-Rad50-Nbs1 complex (MRN) is important for repairing DNA double-strand breaks (DSBs) by homologous recombination (HR). The endonuclease activity of MRN is critical for resecting 5'-ended DNA strands at DSB ends, producing 3'-ended single-strand DNA, a prerequisite for HR. This endonuclease activity is stimulated by Ctp1, the Schizosaccharomyces pombe homolog of human CtIP. Here, with purified proteins, we show that Ctp1 phosphorylation stimulates MRN endonuclease activity by inducing the association of Ctp1 with Nbs1. The highly conserved extreme C terminus of Ctp1 is indispensable for MRN activation. Importantly, a polypeptide composed of the conserved 15 amino acids at the C terminus of Ctp1 (CT15) is sufficient to stimulate Mre11 endonuclease activity. Furthermore, the CT15 equivalent from CtIP can stimulate human MRE11 endonuclease activity, arguing for the generality of this stimulatory mechanism. Thus, we propose that Nbs1-mediated recruitment of CT15 plays a pivotal role in the activation of the Mre11 endonuclease by Ctp1/CtIP. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
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374. A Synthetic Lethality-Based Strategy to Treat Cancers Harboring a Genetic Deficiency in the Chromatin Remodeling Factor BRG1.
- Author
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Takahiro Oike, Hideaki Ogiwara, Yuichi Tominaga, Kentaro Ito, Osamu Ando, Koji Tsuta, Tatsuji Mizukami, Yoko Shimada, Hisanori Isomura, Mayumi Komachi, Koh Furuta, Shun-Ichi Watanabe, Takashi Nakano, Jun Yokota, and Takashi Kohno
- Subjects
- *
CANCER treatment , *CANCER genetics , *CANCER cells , *IMMUNOHISTOCHEMISTRY , *GENETIC mutation , *ADENOSINE triphosphatase gene expression , *XENOGRAFTS - Abstract
The occurrence of inactivating mutations in SWI/SNF chromatin-remodeling genes in common cancers has attracted a great deal of interest. However, mechanistic strategies to target tumor cells carrying such mutations are yet to be developed. This study proposes a synthetic-lethality therapy for treating cancers deficient in the SWI/SNF catalytic (ATPase) subunit, BRG1/SMARCA4. The strategy relies upon inhibition of BRM/SMARCA2, another catalytic SWI/SNF subunitwith a BRG1-related activity. Immunohistochemical analysis of a cohort of non-small-cell lung carcinomas (NSCLC) indicated that 15.5% (16 of 103) of the cohort, corresponding to preferentially undifferentiated tumors, was deficient in BRG1 expression. All BRG1-deficient cases were negative for alterations in known therapeutic target genes, for example, EGFR andDDR2 genemutations, ALK gene fusions, or FGFR1 gene amplifications. RNA interference (RNAi)-mediated silencing of BRM suppressed the growth of BRG1-deficient cancer cells relative to BRG1-proficient cancer cells, inducing senescence via activation of p21/CDKN1A. This growth suppressionwas reversed by transduction ofwild-type but not ATPase-deficient BRG1. In support of these in vitro results, a conditional RNAi study conducted in vivo revealed that BRMdepletion suppressed the growth of BRG1-deficient tumor xenografts. Our results offer a rationale to develop BRM-ATPase inhibitors as a strategy to treat BRG1/SMARCA4-deficient cancers, including NSCLCs that lack mutations in presently known therapeutic target genes. [ABSTRACT FROM AUTHOR]
- Published
- 2013
- Full Text
- View/download PDF
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