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Oxygen sufficiency controls TOP mRNA translation via the TSC-Rheb-mTOR pathway in a 4e-BP-independent manner

Journal of Molecular Cell Biology 2014年第3期8卷 255-266页

作者： Rachel Miloslavski elad Cohen Adam Avraham Yifat I luz Zvi Hayouka judith Kasir Rajini Mudhasani Stephen N. Jones Nadine Cybulski Markus A. Ruegg Ola Larsson Valentina Gandin Arjuna Rajakumar Ivan Topisirovic Oded Meyuhas Department of Biochemistry and Molecular Biology The Institute for Medical Research - Israel-Canada The Hebrew University-Hadassah Medical School Jerusalem 91120 Israel Department of Cell Biology University of Massachusetts Medical School North Worcester MA 01655 USA Biozentrum University of Basel Klingelbergstrasse 70 CH-4056 Basel Switzerland Department of Oncolo'gy-Pathology Karolinska Instituie Stockholm SE-171 76 Sweden Lady Davis Institute for Medical Research Sir Mortimer B. Davis-Jewish General Hospital and Department of Oncology McGill University Montreal QC H3T 1E2 Canada Present address: Migal-Galilee Research Institute Kiryat Shmona 11016 Israel Present address: United States Army Medical Research Institute of Infectious Diseases Frederick MD 21702-5011 USA Present address: ADAM Montreal QC H3N 2C7 Canada

Cells encountering hypoxic stress conserve resources and energy by downregulating the protein synthesis. Here we demonstrate that one mechanism in this response is the translational repression of TOP mRNAs that encode components of the translational apparatus. This mode of regulation involves TSC and Rheb, as knockout of TSC1 or TSC2 or overexpression of Rheb rescued TOP mRNA translation in oxygen-deprived celts. Stress-induced translational repression of these mRNAs closely correlates with the hypophosphorylated state of 4e-BP, a translational repressor. However, a series of 4e-BP loss- and gain-of-function experiments disprove a cause-and- effect relationship between the phosphorylation status of 4e-BP and the translational repression of TOP mRNAs under oxygen or growth factor deprivation. Furthermore, the repressive effect of anoxia is similar to that attained by the very efficient inhibition of mTOR activity by Torin 1, but much more pronounced than roptor or rictor knockouL Likewise, deficiency of raptor or rictor, even though it mildly downregulated basal translation efficiency of TOP mRNAs, failed to suppress the oxygen-mediated translational activation of TOP mRNAs. Finally, co-knockdown of TIA-1 and TIAR, two RNA-binding proteins previously implicated in translational repression of TOP mRNAs in amino acid-starved cells, failed to relieve TOP mRNA translation under other stress conditions. Thus, the nature of the proximal translational regulator of TOP m RNAs remains elusive.

关键词： hypoxia roTOR TOP mRNAs translational control 4e-BP

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Heavy Metals Monitoring in Sediments from Lerma River in West-Central Mexico

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American Journal of Analytical Chemistry 2018年第2期9卷 77-87页

作者： Héctor Hernández-Mendoza María judith Ríos-Lugo elizabeth Teresita Romero-Guzmán Lázaro Raymundo Reyes-Gutiérrez Michael e. Ketterer Instituto Nacional de Investigaciones Nucleares Ocoyoacác México Universidad del Centro de México San Luis Potosí México Universidad Autónoma de San Luis Potosí San Luis Potosí México División of Ciencias Básicas e Ingeniería Departmentof Recursos de la Tierra Universidad Autónoma Metropolitana-Lerma (UAM-L) Lerma México Department of Chemistry Metropolitan State University of Denver Denver USA

The aim of this work was to carry out monitoring of some elements considered toxic in sediments from Lerma River. An analytical method was optimized in our laboratory for quantification of nickel (Ni), cobalt (Co), manganese (Mn), arsenic (As), chromium (Cr) and lead (Pb) by using Inductively Coupled Plasma Optical emission Spectrometry (ICP-OeS). Ten sediments were collected along the Lerma River at variable distances and at 20 cm depth. Samples were heated to 60°C to dryness, followed by separation of particle size using a 74-μ No. 200 mesh for homogeneity purposes. 0.2 g of sample underwent microwave-assisted acid digestion, followed by plate evaporation. The samples were dissolved in 10 mL with HNO3 at 5% v/v for ICP-OeS analysis. A certified reference material (CRM 8704) was used to evaluate the method’s accuracy and precision. The method showed linearity, precision, accuracy, and limits of quantification and detection acceptable for protocol validation of analytical method. The average results obtained in recovery of CRM 8704 were ~90% and precision was below 7% for all elements. Levels concentration of As, Cr, Pb show high pollution in A1, A7 and A8 sites. Therefore, Co, Mn and Ni can be considered in this study as normal values. In conclusion, concentration levels of As, Cr, Pb in sediments were high according to US-ePA and NOM-147-SeMARNAT/SSA1-2004. The presence of these heavy metals in Lerma River could be due mainly for the emitted from industries, such as pharmaceutical, automotive, metal mechanics and tannery, and urban residual water. Finally, the method developed using ICP-OeS has enabled monitoring of these elements in sediments from Lerma River, with possible applications in a routine analytical laboratory.

关键词： ICP-OeS Lerma River Sediments US-ePA

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Food-derived peptides with inhibitory capacity for HMG-CoA reductase activity: a potential nutraceutical for hypercholesterolemia

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Food Science and Human Wellness 2023年

作者： Guillermo Santos-Sánchez Ana Isabel álvarez-López eduardo Ponce-espa?a Patricia judith Lardone Antonio Carrillo-Vico Ivan Cruz-Chamorro Instituto de Biomedicina de Sevilla IBiS (Universidad de Sevilla， HUVR， Junta de Andalucía，CSIC) Departamento de Bioquímica Médica y Biología Molecular e Inmunología， Universidad de Sevilla

Cardiovascular diseases (CVDs) are the leading global cause of mortality and disease burden. Statins are the most prescribed lipid-lowering drugs to treat hypercholesterolemia and prevent CVDs. The biochemical mechanism of statins consists of competitive inhibition of the 3-hydroxy-3-methylglutaryl-CoA reductase enzyme (HMG-CoAR)， the limiting enzyme in cholesterol biosynthesis. Due to statin intolerance in some patient groups， the search for new inhibitors is a field of great interest. This review focusses on the studies reporting the inhibitory effect of protein hydrolysates and biopeptides on the HMG-CoAR enzyme activity. The analysis of the action mechanism and physicochemical characteristics of the HMG-CoAR inhibitory peptides revealed that the molecular weight， amino acid composition， charge， and polarity are key aspects of the interaction with the HMG-CoAR enzyme. In conclusion， this review reveals the potential of using food peptides as new cholesterol-lowering agents and opens a new interesting field of research. However， clinical approaches are mandatory to confirm their therapeutic hypercholesterolemic effect.

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制药企业药品上市前安全风险管理

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药物流行病学杂志 2013年第5期22卷 266-273页

作者： judith K Jones elyse e Kingery Jing Tao Jeff J Guo 美国弗吉尼亚州Degge集团公司美国阿林顿22209 美国辛辛那提大学医学中心美国辛辛那提大学药学院药物实践及管理科学部

1药物警戒的必要性良好的药物警戒是最理想的药品风险管理方式,它可以最大程度的了解某种药品的所有信息,并且发现它潜在的安全问题,甚至有可能发现其预料之外的好处。鉴于这个理念,新化学实体（newchemical entity）在研发初期就必须... 详细信息

1药物警戒的必要性良好的药物警戒是最理想的药品风险管理方式,它可以最大程度的了解某种药品的所有信息,并且发现它潜在的安全问题,甚至有可能发现其预料之外的好处。鉴于这个理念,新化学实体（newchemical entity）在研发初期就必须进行动物和人体安全性测试,以便更好地促进并保护公众健康。中国古话所说的＂是药三分毒＂,

关键词：上市前安全风险管理药物警戒安全性有效性安全评估

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An Ongoing epidemic of Birth Defects

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Pharmacology & Pharmacy 2013年第3期4卷 312-317页

作者： Gladys Cossio Alberto Bissot Mireya de Rivas Luis Morales Paul Gallardo David ellis judith Hall Neonatology Ward and Genetics Department Hospital del Nino de Panama(Panama’s Children’s Hospital)Panama CityRepublic of Panama Department of Pediatrics University of British ColumbiaVancouverCanada

In the 1990s, misoprostol (synthetic prostaglandin e1 analogue) was found to be an effective abortive agent when taken orally and became widely used in Latin America as a means to terminate unwanted pregnancies. A variety of congenital anomalies have been observed among the children of women who ingested misoprostol, but failed to terminate their pregnancy. We report here eight years of experience in Panama with the detection and follow-up of the malformations seen in infants associated with the use of misoprostol prostaglandin during the first trimester of pregnancy. During the period between April 1995 and March 2003, we identified 63 infants at the Panama’s Children’s Hospital who were exposed to misoprostol while in the womb and who were born with malformations. These infants were evaluated by a team of neonatologists, geneticists, cardiologists, ophthalmologists, and radiologists.

关键词： Congenital Anomalies Teratogenic Agent Misoprostol Pregnancy

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温柔的胜利

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1993年

作者：茱迪·麦娜(judith McNaught)原

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Immunoscreening of Alpha-Tocopherol in Breast, Prostate Cancers and in Gestational Choriocarcinoma Tissues

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CellBio 2021年第2期10卷 11-21页

作者： Henriette Poaty Franck Arnaud Moukobolo Kinsangou Alexis F. Bolenga Liboko judith Nsonde Malanda Michel Geffard Faculty of Health Sciences Marien Ngouabi University Brazzaville Congo National Research Institute on Health Sciences (IRSSA) Brazzaville Congo Oncology Service Teaching hospital Brazzaville Congo Institut pour le Développement de la Recherche en Pathologie Humaine et Thérapeutique Talence France

Background: Many literature reviews report vitamin e supplementation as a benefit chemopreventive and adjuvant therapy in breast and prostate cancers. We investigated in the present work, alpha-tocopherol (α-T) expression (the current active form of vitamin e) from tissues of Congolese patients neither smokers nor alcohol drinkers and without intake antioxidant vitamins supplement. Methods: α-T was analysed in one normal placenta of nine weeks of gestation and in nineteen cancerous tissues, including seven breast cancers, six prostate cancers, and six gestational choriocarcinomas. The study was performed by immunohistochemistry method after diagnosis confirmation by histological analysis. Results: α-T staining in membrane cells and collagen fibers presented a moderate expression in healthy sections of tissues (positive control), but the labelling was strong in breast, prostate adenocarcinomas, and in choriocarcinomas. Conclusion: Tumors immunohistochemistry of α-tocopherol in breast, prostate cancers and in choriocarcinoma show elevated immunostaining suggesting a probable oncogenic effect of the micronutrient.

关键词： Vitamin e Alpha-Tocopherol Immunohistochemistry Breast Cancer Prostate Cancer Choriocarcinoma

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Sodium Diffuses from Glass Substrates through P1 Lines and Passivates Defects in Perovskite Solar Modules

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energy & environmental Materials 2023年第6期6卷 393-401页

作者： Felix Utama Kosasih Francesco Di Giacomo Jordi Ferrer Orri Kexue Li elizabeth M.Tennyson Weiwei Li Fabio Matteocci Gunnar Kusch Narges Yaghoobi Nia Rachel A.Oliver judith L.MacManus-Driscoll Katie L.Moore Samuel D.Stranks Aldo Di Carlo Giorgio Divitini Caterina Ducati Department of Materials Science and Metallurgy University of Cambridge27 Charles Babbage RoadCambridge CB30FSUK Centre for Hybrid and Organic Solar energy(CHOSe) Department of Electronic EngineeringUniversity of Rome Tor VergataRome 00133Italy Cavendish Laboratory University of CambridgeJJ Thomson AvenueCambridge CB30HEUK Department of Materials and Photon Science Institute University of ManchesterOxford RoadManchester M139PLUK Department of Chemical engineering and Biotechnology University of CambridgePhilippa Fawcett DriveCambridge CB30ASUK Laboratory for Advanced Solar energy(LASe) National University of Science and Technology MISiSLeninskiy Prospekt 4Moscow 119049Russia energy Research Institute@NTU Nanyang Technological University50 Nanyang DriveSingapore 637553Singapore MIIT Key Laboratory of Aerospace Information Materials and Physics College of PhysicsNanjing University of Aeronautics and AstronauticsNanjing 211106China Istituto di Struttura della Materia-CNR(ISM-CNR) Via del Fosso del Cavaliere 100Rome 00133Italy electron Spectroscopy and Nanoscopy Istituto Italiano di TecnologiaVia Morego 30Genova 16163Italy

Most thin-film photovoltaic modules are constructed on soda-lime glass(SLG)substrates containing alkali oxides,such as Na_(2)*** may diffuse from SLG into a module's active layers through P1 lines,an area between a module's constituent cells where the substrate-side charge transport layer(CTL)is in direct contact with *** diffusion from SLG is known to cause several important effects inⅡ-Ⅵand chalcogenide solar modules,but it has not been studied in perovskite solar modules(PSMs).In this work,we use complementary microscopy and spectroscopy techniques to show that Na diffusion occurs in the fabrication process of *** diffuses vertically inside P1 lines and then laterally from P1 lines into the active area for up to 360 *** propose that this process is driven by the high temperatures the devices are exposed to during CTL and perovskite *** diffused Na preferentially binds with Br,forming Br-poor,l-rich perovskite and a species rich in Na and Br(Na-Br)close to P1 ***-Br passivates defect sites,reducing non-radiative recombination in the perovskite and boosting its luminescence by up to 5×.Na-Br is observed to be stable after 12 weeks of device storage,suggesting long-lasting effects of Na *** results not only point to a potential avenue to increase PSM performance but also highlight the possibility of unabated Na diffusion throughout a module's lifetime,especially if accelerated by the electric field and elevated temperatures achievable during device operation.

关键词： defect passivation monolithic interconnection perovskite solar modules soda-lime glass sodium diffusion solar cells thin-film photovoltaics

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Introduction to geography 7th ed.

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2000年

作者： Arthur Getis judith Getis Jerome D. Fellmann.

来源：畅想之星图书光盘版（南... 评论

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世界卫生组织、联合国艾滋病规划署瑞士日内瓦

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城市建筑 2008年第9期5卷 81-83页

作者： Axel Simon judith Wolfframm

该项目坐落于众多国际组织云集的小山丘上，可俯视日内瓦城的历史文化中心以及湖光山色。该项目主题是对现有物质条件和特殊地形下的自然区域做一次有价值的研究。当然，尽管需要考虑城市的规划要求，但设计的另一大理念就是最大程度地... 详细信息

该项目坐落于众多国际组织云集的小山丘上，可俯视日内瓦城的历史文化中心以及湖光山色。该项目主题是对现有物质条件和特殊地形下的自然区域做一次有价值的研究。当然，尽管需要考虑城市的规划要求，但设计的另一大理念就是最大程度地优化办公楼与外部景观的关系。在设计中，B＋e的设计师们为解决与现有高层建筑相互对应的设计问题上做出了回答设计”卧式“建筑，使两栋楼平行对视、遥相呼应、保持彼此间适度的距离。地形延伸至老楼所在的高地下面，而新楼的洼地和庭院也扩展了绿化面积。重要的是，紧凑的建筑体量使三个主要部分紧密分布在三处基点上。

关键词：世界卫生组织日内瓦规划艾滋病联合国设计问题瑞士高层建筑

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