WorldWideScience

Sample records for junning cai pingsun

  1. Competition in Individualized CAI.

    Science.gov (United States)

    Hativa, Nira; And Others

    1993-01-01

    Examines the effects of competition and cooperation on learning through computer-assisted instruction (CAI). A questionnaire was administered to 457 Israeli fourth graders who used two CAI arithmetic systems. The characteristics of the systems are discussed, and the results of the survey are correlated to students' gender and achievement levels.…

  2. Maxi CAI with a Micro.

    Science.gov (United States)

    Gerhold, George; And Others

    This paper describes an effective microprocessor-based CAI system which has been repeatedly tested by a large number of students and edited accordingly. Tasks not suitable for microprocessor based systems (authoring, testing, and debugging) were handled on larger multi-terminal systems. This approach requires that the CAI language used on the…

  3. Timing Students' Answers in CAI.

    Science.gov (United States)

    Hativa, Nira; And Others

    1991-01-01

    Discussion of limiting response time for students' answers focuses on a study of Israeli elementary students that investigated the effects on their performance of increasing the response time in computer-assisted instruction (CAI) for arithmetic drill and practice. Effects on high- versus low-aptitude students, and younger versus older, are…

  4. A unified framework for producing CAI melting, Wark-Lovering rims and bowl-shaped CAIs

    Science.gov (United States)

    Liffman, Kurt; Cuello, Nicolas; Paterson, David A.

    2016-10-01

    Calcium-Aluminium inclusions (CAIs) formed in the Solar system, some 4567 million years ago. CAIs are almost always surrounded by Wark-Lovering rims (WLRs), which are a sequence of thin, mono/bi-mineralic layers of refractory minerals, with a total thickness in the range of 1-100 microns. Recently, some CAIs have been found that have tektite-like bowl-shapes. To form such shapes, the CAI must have travelled through a rarefied gas at hypersonic speeds. We show how CAIs may have been ejected from the inner solar accretion disc via the centrifugal interaction between the solar magnetosphere and the inner disc rim. They subsequently punched through the hot, inner disc rim wall at hypersonic speeds. This re-entry heating partially or completely evaporated the CAIs. Such evaporation could have significantly increased the metal abundances of the inner disc rim. High speed movement through the inner disc produced WLRs. To match the observed thickness of WLRs required metal abundances at the inner disc wall that are of order 10 times that of standard solar abundances. The CAIs cooled as they moved away from the protosun, the deduced CAI cooling rates are consistent with the CAI cooling rates obtained from experiment and observation. The speeds and gas densities required to form bowl-shaped CAIs are also consistent with the expected speeds and gas densities for larger, ˜1 cm, CAIs punching through an inner accretion disc wall.

  5. A risk management approach to CAIS development

    Science.gov (United States)

    Hart, Hal; Kerner, Judy; Alden, Tony; Belz, Frank; Tadman, Frank

    1986-01-01

    The proposed DoD standard Common APSE Interface Set (CAIS) was developed as a framework set of interfaces that will support the transportability and interoperability of tools in the support environments of the future. While the current CAIS version is a promising start toward fulfilling those goals and current prototypes provide adequate testbeds for investigations in support of completing specifications for a full CAIS, there are many reasons why the proposed CAIS might fail to become a usable product and the foundation of next-generation (1990'S) project support environments such as NASA's Space Station software support environment. The most critical threats to the viability and acceptance of the CAIS include performance issues (especially in piggybacked implementations), transportability, and security requirements. To make the situation worse, the solution to some of these threats appears to be at conflict with the solutions to others.

  6. Analysis list: Jun [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Jun Blood,Digestive tract,Embryonic fibroblast,Muscle,Pluripotent stem cell + mm9 h...ttp://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Jun.1.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Jun....5.tsv http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/target/Jun.10.tsv http://dbarchive.bioscie...ncedbc.jp/kyushu-u/mm9/colo/Jun.Blood.tsv,http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Jun....Digestive_tract.tsv,http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/colo/Jun.Embryonic_fibro

  7. The Relevance of AI Research to CAI.

    Science.gov (United States)

    Kearsley, Greg P.

    This article provides a tutorial introduction to Artificial Intelligence (AI) research for those involved in Computer Assisted Instruction (CAI). The general theme is that much of the current work in AI, particularly in the areas of natural language understanding systems, rule induction, programming languages, and socratic systems, has important…

  8. A Unified Framework for Producing CAI Melting, Wark-Lovering Rims and Bowl-Shaped CAIs

    CERN Document Server

    Liffman, Kurt; Paterson, David A

    2016-01-01

    Calcium Aluminium Inclusions (CAIs) formed in the Solar System, some 4,567 million years ago. CAIs are almost always surrounded by Wark-Lovering Rims (WLRs), which are a sequence of thin, mono/bi-mineralic layers of refractory minerals, with a total thickness in the range of 1 to 100 microns. Recently, some CAIs have been found that have tektite-like bowl-shapes. To form such shapes, the CAI must have travelled through a rarefied gas at hypersonic speeds. We show how CAIs may have been ejected from the inner solar accretion disc via the centrifugal interaction between the solar magnetosphere and the inner disc rim. They subsequently punched through the hot, inner disc rim wall at hypersonic speeds. This re-entry heating partially or completely evaporated the CAIs. Such evaporation could have significantly increased the metal abundances of the inner disc rim. High speed movement through the inner disc produced WLRs. To match the observed thickness of WLRs required metal abundances at the inner disc wall that a...

  9. NALDA (Naval Aviation Logistics Data Analysis) CAI (computer aided instruction)

    Energy Technology Data Exchange (ETDEWEB)

    Handler, B.H. (Oak Ridge K-25 Site, TN (USA)); France, P.A.; Frey, S.C.; Gaubas, N.F.; Hyland, K.J.; Lindsey, A.M.; Manley, D.O. (Oak Ridge Associated Universities, Inc., TN (USA)); Hunnum, W.H. (North Carolina Univ., Chapel Hill, NC (USA)); Smith, D.L. (Memphis State Univ., TN (USA))

    1990-07-01

    Data Systems Engineering Organization (DSEO) personnel developed a prototype computer aided instruction CAI system for the Naval Aviation Logistics Data Analysis (NALDA) system. The objective of this project was to provide a CAI prototype that could be used as an enhancement to existing NALDA training. The CAI prototype project was performed in phases. The task undertaken in Phase I was to analyze the problem and the alternative solutions and to develop a set of recommendations on how best to proceed. The findings from Phase I are documented in Recommended CAI Approach for the NALDA System (Duncan et al., 1987). In Phase II, a structured design and specifications were developed, and a prototype CAI system was created. A report, NALDA CAI Prototype: Phase II Final Report, was written to record the findings and results of Phase II. NALDA CAI: Recommendations for an Advanced Instructional Model, is comprised of related papers encompassing research on computer aided instruction CAI, newly developing training technologies, instructional systems development, and an Advanced Instructional Model. These topics were selected because of their relevancy to the CAI needs of NALDA. These papers provide general background information on various aspects of CAI and give a broad overview of new technologies and their impact on the future design and development of training programs. The paper within have been index separately elsewhere.

  10. Marshall McLuhan and the Case Against CAI.

    Science.gov (United States)

    Hirvela, Alan

    1988-01-01

    Presents some of the conventional arguments against computer assisted instruction (CAI) in language education and explores humanistic concerns raised in the works of Marshall McLuhan. It is concluded that CAI is introduced into the instructional process before proper research has demonstrated that this method of teaching is not harmful for…

  11. Effect of CAI on Achievement of LD Students in English

    Science.gov (United States)

    Sivaram, R. T.; Ramar, R.

    2014-01-01

    The present experimental study was undertaken with three objectives in view, (i) to identify students with language learning disabilities (ii) to develop CAI software to teach LD students through computer-assisted instruction and (iii) to measure the effectiveness of CAI with special reference to LD students. Two matched groups of LD students were…

  12. A Pilot CAI Scheme for the Malaysian Secondary Education System.

    Science.gov (United States)

    Rao, A. Kanakaratnam; Rao, G. S.

    1982-01-01

    A multi-phase computer aided instruction (CAI) scheme for Malaysian Secondary Schools and Matriculation Centres attached to local universities is presented as an aid for improving instruction and for solving some problems presently faced by the Malaysian Secondary Education System. Some approaches for successful implementation of a CAI scheme are…

  13. CAI vs. Textbook for Grammar and Punctuation Skills.

    Science.gov (United States)

    Schramm, Robert M.; Rich, Grace E.

    1993-01-01

    Undergraduate control groups (n=45) completed textbook grammar exercises; experimental groups (n=53) used self-paced tutorial/drill-and-practice software. Although students using computer-assisted instruction (CAI) made significant improvement, they had reservations about the method. CAI combined with instructor interaction seem to be a feasible…

  14. Acetylation regulates Jun protein turnover in Drosophila.

    Science.gov (United States)

    Zhang, Daoyong; Suganuma, Tamaki; Workman, Jerry L

    2013-11-01

    C-Jun is a major transcription factor belonging to the activating protein 1 (AP-1) family. Phosphorylation has been shown to be critical for c-Jun activation and stability. Here, we report that Jra, the Drosophila Jun protein, is acetylated in vivo. We demonstrate that the acetylation of Jra leads to its rapid degradation in response to osmotic stress. Intriguingly, we also found that Jra phosphorylation antagonized its acetylation, indicating the opposite roles of acetylation and phosphorylation in Jra degradation process under osmotic stress. Our results provide new insights into how c-Jun proteins are precisely regulated by the interplay of different posttranslational modifications.

  15. Cai-Li Communication Protocol in Noisy Quantum Channel

    Institute of Scientific and Technical Information of China (English)

    L(U) Hua; YAN Xu-Dong; ZHANG Xian-Zhou

    2004-01-01

    @@ Since the original Cai-Li protocol [Chin. Phys. Lett. 21 (2004) 601] can be used only in an ideal quantum communication, we present the modified Cai-Li protocol that can be used in the a noisy quantum channel by using Calderbank-Shor-Steane (CSS) codes to correct errors. We also give a tight bound on the connection between information Eve eavesdropped with a measurement attack in line B → A and detection probability,which shows that the Cai-Li protocol can be used as a quasisecure direct quantum communication.

  16. Study on Teaching Strategies in Mathematics Education based on CAI

    Directory of Open Access Journals (Sweden)

    Wei Yan Feng

    2016-01-01

    Full Text Available With the development of information technology and the popularization of internet, mobile phone, new media represented is gradually influencing and changing people’s study and life, become the centre and social consensus of cultural information, according to the China Internet Network Information centre, the youth is the main use of CAI(Computer Assisted Instruction, which is the most active group of customers, fully understand the impact of the new media environment for students, higher mathematics education of college students in CAI. In this paper, the CAI is proposed for mathematics education of college students.

  17. CAI System of Obunsha Co., Ltd. Using CD-ROM

    Science.gov (United States)

    Todokoro, Shigeru; Mukai, Yoshihiro

    This paper introduces the present status of R & D on CAI teaching materials in Obunsha Co., Ltd. Characteristics of CAI using CD-ROM as well as Culture-in CAI Teaching Materials System for junior high school English are described. The system consists of CD-ROM driver XM-2000 and Pasopia 700 of Toshiba Corporation having both features of CD-ROM and FD. CD-ROM stores vast amount of voice data while FD does text and graphics data. It is a frame-oriented mode system enabling to raise learning effect.

  18. Oncogene v-jun modulates DNA replication.

    Science.gov (United States)

    Wasylyk, C; Schneikert, J; Wasylyk, B

    1990-07-01

    Cell transformation leads to alterations in both transcription and DNA replication. Activation of transcription by the expression of a number of transforming oncogenes is mediated by the transcription factor AP1 (Herrlich & Ponta, 1989; Imler & Wasylyk, 1989). AP1 is a composite transcription factor, consisting of members of the jun and fos gene-families. c-jun and c-fos are progenitors of oncogenes, suggestion that an important transcriptional event in cell transformation is altered activity of AP1, which may arise either indirectly by oncogene expression or directly by structural modification of AP1. We report here that the v-jun oncogene and its progenitor c-jun, as fusion proteins with the lex-A-repressor DNA binding domain, can activate DNA replication from the Polyoma virus (Py) origin of replication, linked to the lex-A operator. The transcription-activation region of v-jun is required for activation of replication. When excess v-jun is expressed in the cell, replication is inhibited or 'squelched'. These results suggest that one consequence of deregulated jun activity could be altered DNA replication and that there are similarities in the way v-jun activates replication and transcription.

  19. A CAI in the Ivuna CI1 Chondrite

    Science.gov (United States)

    Frank, David R.; Zolensky, M.; Martinez, J.; Mikouchi, T.; Ohsumi, K.; Hagiya, K.; Satake, W.; Le, L.; Ross, D.; Peslier, A.

    2011-01-01

    We have recently discovered the first well-preserved calcium aluminum-rich inclusion (CAI) in a CI1 chondrite (Ivuna). Previously, all CI1 chondrites were thought to be devoid of preserved CAI and chondrules due to the near total aqueous alteration to which their parent body (bodies) have been subjected. The CAI is roughly spherical, but with a slight teardrop geometry and a maximum diameter of 170 microns (fig. 1). It lacks any Wark-Lovering Rim. Incipient aqueous alteration, and probably shock, have rendered large portions of the CAI poorly crystalline. It is extremely fine-grained, with only a few grains exceeding 10 microns. We have performed electron microprobe analyses (EPMA), FEG-SEM imaging and element mapping, as well as electron back-scattered diffraction (EBSD) and synchrotron X-ray diffraction (SXRD) in order to determine the fundamental characteristics of this apparently unique object.

  20. NANOG upregulates c-Jun oncogene expression through binding the c-Jun promoter.

    Science.gov (United States)

    Lin, Yanli; Xiong, Fuyin; Zhou, Yanrong; Wu, Xiaojie; Liu, Fang; Xue, Shiwei; Chen, Hongxing

    2015-11-01

    NANOG plays important roles in neoplastic processes. However, the molecular mechanism of NANOG in tumorigenesis remains to be elucidated. In this report, we demonstrated that forced expression of NANOG in 293 cells and cancer cells led to increased c-Jun expression, whereas downregulation of endogenous NANOG significantly reduced c-Jun expression in cancer cells. Dual luciferase reporter assays demonstrated that NANOG binds the c-Jun proximal promoter and transactivates the c-Jun gene. An ATTA consensus motif between the -160 and -268 region of the c-Jun promoter was identified as the NANOG-responsive element. Electromobility shift assay and chromatin immunoprecipitation results confirmed the direct binding of NANOG protein to the c-Jun promoter in vitro and in vivo. NANOG directly bound c-Jun protein as shown by GST pulldown and immunoprecipitation assays. Taking these findings together, we conclude that c-Jun is a direct target gene of NANOG and that c-Jun protein may be a novel co-activator of NANOG in cancer cells. We suggest the possibility that NANOG may play a significant role in carcinogenesis via its activation of c-Jun expression.

  1. c-Jun promotes whereas JunB inhibits epidermal neoplasia.

    Science.gov (United States)

    Jin, Jane Y; Ke, Hengning; Hall, Russell P; Zhang, Jennifer Y

    2011-05-01

    Deregulation of the activator protein 1 (AP1) family gene regulators has been implicated in a wide range of diseases, including cancer. In this study we report that c-Jun was activated in human squamous cell carcinoma (SCC) and coexpression of c-Jun with oncogenic Ras was sufficient to transform primary human epidermal cells into malignancy in a regenerated human skin grafting model. In contrast, JunB was not induced in a majority of human SCC cells. Moreover, exogenous expression of JunB inhibited tumorigenesis driven by Ras or spontaneous human SCC cells. Conversely, the dominant-negative JunB mutant (DNJunB) promoted tumorigenesis, which is in contrast to the tumor-suppressor function of the corresponding c-Jun mutant. At the cellular level, JunB induced epidermal cell senescence and slowed cell growth in a cell-autonomous manner. Consistently, coexpression of JunB and Ras induced premature epidermal differentiation concomitant with upregulation of p16 and filaggrin and downregulation of cyclin D1 and cyclin-dependent kinase 4 (CDK4). These findings indicate that JunB and c-Jun differentially regulate cell growth and differentiation and induce opposite effects on epidermal neoplasia.JID JOURNAL CLUB ARTICLE: For questions, answers, and open discussion about this article, please go to http://www.nature.com/jid/journalclub.

  2. Control strategies for CAI combustion processes; Strategien zur Regelung von CAI-Brennverfahren

    Energy Technology Data Exchange (ETDEWEB)

    Karrelmeyer, R.; Graf, G.; Scherrer, D.; Fischer, W.; Hathout, J.P. [Robert Bosch GmbH, Stuttgart (Germany)

    2008-07-01

    The contribution presents concepts for control of a CAI combustion process with internal exhaust trapping. The concepts are based on combustion characteristics obtained from the combustion chamber pressure signal. Combustion is controlled using the control variables of the air and fuel systems. The engines investigated were engines with variable valve drive, with different degrees of variability, and with a direct injection system. In a first step, a fully variable valve control system is investigated which enables adjustment of the gas change valves for the individual cylinders. In the second step, the cost aspect is considered and a control strategy is presented which does not control individual cylinders but uses a valve control strategy with conventional phase control elements. The control concepts presented here are a combination of pre-control and combustion characteristics control. Results obtained during operating mode switching, dynamic operation and stabilisation of the CAI mode are presented as well. Pre-control is particularly important in order to prevent misfires as well as extremely early and loud combustion both in dynamic operation and during switching. (orig.)

  3. c-Jun Promotes whereas JunB Inhibits Epidermal Neoplasia

    OpenAIRE

    Jin, Jane Yingai; Ke, Hengning; Hall, Russell P.; Zhang, Jennifer Y.

    2011-01-01

    Deregulation of the AP1 family gene regulators have been implicated in a wide range of diseases, including cancer. Here, we report that c-Jun was activated in human squamous cell carcinoma (SCC) and coexpression of c-Jun with oncogenic Ras was sufficient to transform primary human epidermal cells into malignancy in a regenerated human skin grafting model. In contrast, JunB was not induced in a majority of human SCC cells. Moreover, exogenous expression of JunB inhibited tumorigenesis driven b...

  4. Numerical simulation and validation of SI-CAI hybrid combustion in a CAI/HCCI gasoline engine

    Science.gov (United States)

    Wang, Xinyan; Xie, Hui; Xie, Liyan; Zhang, Lianfang; Li, Le; Chen, Tao; Zhao, Hua

    2013-02-01

    SI-CAI hybrid combustion, also known as spark-assisted compression ignition (SACI), is a promising concept to extend the operating range of CAI (Controlled Auto-Ignition) and achieve the smooth transition between spark ignition (SI) and CAI in the gasoline engine. In this study, a SI-CAI hybrid combustion model (HCM) has been constructed on the basis of the 3-Zones Extended Coherent Flame Model (ECFM3Z). An ignition model is included to initiate the ECFM3Z calculation and induce the flame propagation. In order to precisely depict the subsequent auto-ignition process of the unburned fuel and air mixture independently after the initiation of flame propagation, the tabulated chemistry concept is adopted to describe the auto-ignition chemistry. The methodology for extracting tabulated parameters from the chemical kinetics calculations is developed so that both cool flame reactions and main auto-ignition combustion can be well captured under a wider range of thermodynamic conditions. The SI-CAI hybrid combustion model (HCM) is then applied in the three-dimensional computational fluid dynamics (3-D CFD) engine simulation. The simulation results are compared with the experimental data obtained from a single cylinder VVA engine. The detailed analysis of the simulations demonstrates that the SI-CAI hybrid combustion process is characterised with the early flame propagation and subsequent multi-site auto-ignition around the main flame front, which is consistent with the optical results reported by other researchers. Besides, the systematic study of the in-cylinder condition reveals the influence mechanism of the early flame propagation on the subsequent auto-ignition.

  5. c-Jun N-terminal kinase - c-Jun pathway transactivates Bim to promote osteoarthritis.

    Science.gov (United States)

    Ye, Zhiqiang; Chen, Yuxian; Zhang, Rongkai; Dai, Haitao; Zeng, Chun; Zeng, Hua; Feng, Hui; Du, Gengheng; Fang, Hang; Cai, Daozhang

    2014-02-01

    Osteoarthritis (OA) is a chronic degenerative joint disorder. Previous studies have shown abnormally increased apoptosis of chondrocytes in patients and animal models of OA. TNF-α and nitric oxide have been reported to induce chondrocyte ageing; however, the mechanism of chondrocyte apoptosis induced by IL-1β has remained unclear. The aim of this study is to identify the role of the c-Jun N-terminal kinase (JNK) - c-Jun pathway in regulating induction of Bim, and its implication in chondrocyte apoptosis. This study showed that Bim is upregulated in chondrocytes obtained from the articular cartilage of OA patients and in cultured mouse chondrocytes treated with IL-1β. Upregulation of Bim was found to be critical for chondrocyte apoptosis induced by IL-1β, as revealed by the genetic knockdown of Bim, wherein apoptosis was greatly reduced in the chondrocytes. Moreover, activation of the JNK-c-Jun pathway was observed under IL-1β treatment, as indicated by the increased expression levels of c-Jun protein. Suppression of the JNK-c-Jun pathway, using chemical inhibitors and RNA interference, inhibited the Bim upregulation induced by IL-1β. These findings suggest that the JNK-c-Jun pathway is involved in the upregulation of Bim during OA and that the JNK-c-Jun-Bim pathway is vital for chondrocyte apoptosis.

  6. Prof. Cai Shuming Receives 2005 Wetland Conservation Award

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    @@ Prof. Cai Shuming, an expert in wetland studies from the CAS Institute of Geodesy & Geophysics, has been honored with a Ramsar Wetland Conservation Award in 2005. The announcement was made by the Standing Committee of the Ramsar Convention on June 10 in Gland,Switzerland.

  7. Distribution and Origin of 36Cl In Allende CAIs

    Energy Technology Data Exchange (ETDEWEB)

    Matzel, J P; Jacobsen, B; Hutcheon, I D; Krot, A N; Nagashima, K; Yin, Q; Ramon, E C; Weber, P; Wasserburg, G J

    2009-12-11

    The abundance of short-lived radionuclides (SLRs) in early solar system materials provide key information about their nucleosynthetic origin and can constrain the timing of early solar system events. Excesses of {sup 36}S ({sup 36}S*) correlated with {sup 35}Cl/{sup 34}S ratios provide direct evidence for in situ decay of {sup 36}Cl ({tau}{sub 1/2} {approx} 0.3 Ma) and have been reported in sodalite (Na{sub 8}Al{sub 6}Si{sub 6}O{sub 24}Cl{sub 2}) and wadalite (Ca{sub 6}Al{sub 5}Si{sub 2}O{sub 16}Cl{sub 3}) in CAIs and chondrules from the Allende and Ningqiang CV carbonaceous chondrites. While previous studies demonstrate unequivocally that {sup 36}Cl was extant in the early solar system, no consensus on the origin or initial abundance of {sup 36}Cl has emerged. Understanding the origin of {sup 36}Cl, as well as the reported variation in the initial {sup 36}Cl/{sup 35}Cl ratio, requires addressing when, where and how chlorine was incorporated into CAIs and chondrules. These factors are key to distinguishing between stellar nucleosynthesis or energetic particle irradiation for the origin of {sup 36}Cl. Wadalite is a chlorine-rich secondary mineral with structural and chemical affinities to grossular. The high chlorine ({approx}12 wt%) and very low sulfur content (<<0.01 wt%) make wadalite ideal for studies of the {sup 36}Cl-{sup 36}S system. Wadalite is present in Allende CAIs exclusively in the interior regions either in veins crosscutting melilite or in zones between melilite and anorthite associated with intergrowths of grossular, monticellite, and wollastonite. Wadalite and sodalite most likely resulted from open-system alteration of primary minerals with a chlorine-rich fluid phase. We recently reported large {sup 36}S* correlated with {sup 35}Cl/{sup 34}S in wadalite in Allende Type B CAI AJEF, yielding a ({sup 36}Cl/{sup 35}Cl){sub 0} ratio of (1.7 {+-} 0.3) x 10{sup -5}. This value is the highest reported {sup 36}Cl/{sup 35}Cl ratio and is {approx}5 times

  8. Du Bollettino del CAI à la revue Le Alpi

    Directory of Open Access Journals (Sweden)

    Jean-Paul Zuanon

    2001-05-01

    Full Text Available Comme les autres clubs alpins créés à la même époque, le CAI s’est rapidement doté d’outils de communication pour établir un lien entre ses membres et faire connaître sa philosophie en matière de pratique de la montagne.   Fondé en 1865, le bulletin trimestriel a été complété par la Rivista mensile en 1881. De fait,  l’organe du CAI est vieux de près de 140 ans.  Il est un reflet fidèle de l’évolution du club et des grands débats qui l’ont animé. Sans prétendre retracer cette longue histoire,...

  9. Study on Teaching Strategies in Mathematics Education based on CAI

    OpenAIRE

    Wei Yan Feng

    2016-01-01

    With the development of information technology and the popularization of internet, mobile phone, new media represented is gradually influencing and changing people’s study and life, become the centre and social consensus of cultural information, according to the China Internet Network Information centre, the youth is the main use of CAI(Computer Assisted Instruction), which is the most active group of customers, fully understand the impact of the new media environment for students, higher mat...

  10. Selection and characterization of a DNA aptamer that can discriminate between cJun/cJun and cJun/cFos.

    Directory of Open Access Journals (Sweden)

    Ryan D Walters

    Full Text Available The AP-1 family of transcriptional activators plays pivotal roles in regulating a wide range of biological processes from the immune response to tumorigenesis. Determining the roles of specific AP-1 dimers in cells, however, has remained challenging because common molecular biology techniques are unable to distinguish between the role of, for example, cJun/cJun homodimers versus cJun/cFos heterodimers. Here we used SELEX (systematic evolution of ligands by exponential enrichment to identify and characterize DNA aptamers that are >100-fold more specific for binding cJun/cJun compared to cJun/cFos, setting the foundation to investigate the biological functions of different AP-1 dimer compositions.

  11. Silicon Isotopic Fractionation of CAI-like Vacuum Evaporation Residues

    Energy Technology Data Exchange (ETDEWEB)

    Knight, K; Kita, N; Mendybaev, R; Richter, F; Davis, A; Valley, J

    2009-06-18

    Calcium-, aluminum-rich inclusions (CAIs) are often enriched in the heavy isotopes of magnesium and silicon relative to bulk solar system materials. It is likely that these isotopic enrichments resulted from evaporative mass loss of magnesium and silicon from early solar system condensates while they were molten during one or more high-temperature reheating events. Quantitative interpretation of these enrichments requires laboratory determinations of the evaporation kinetics and associated isotopic fractionation effects for these elements. The experimental data for the kinetics of evaporation of magnesium and silicon and the evaporative isotopic fractionation of magnesium is reasonably complete for Type B CAI liquids (Richter et al., 2002, 2007a). However, the isotopic fractionation factor for silicon evaporating from such liquids has not been as extensively studied. Here we report new ion microprobe silicon isotopic measurements of residual glass from partial evaporation of Type B CAI liquids into vacuum. The silicon isotopic fractionation is reported as a kinetic fractionation factor, {alpha}{sub Si}, corresponding to the ratio of the silicon isotopic composition of the evaporation flux to that of the residual silicate liquid. For CAI-like melts, we find that {alpha}{sub Si} = 0.98985 {+-} 0.00044 (2{sigma}) for {sup 29}Si/{sup 28}Si with no resolvable variation with temperature over the temperature range of the experiments, 1600-1900 C. This value is different from what has been reported for evaporation of liquid Mg{sub 2}SiO{sub 4} (Davis et al., 1990) and of a melt with CI chondritic proportions of the major elements (Wang et al., 2001). There appears to be some compositional control on {alpha}{sub Si}, whereas no compositional effects have been reported for {alpha}{sub Mg}. We use the values of {alpha}Si and {alpha}Mg, to calculate the chemical compositions of the unevaporated precursors of a number of isotopically fractionated CAIs from CV chondrites whose

  12. The Intelligent CAI System for Chemistry Based on Automated Reasoning

    Institute of Scientific and Technical Information of China (English)

    王晓京; 张景中

    1999-01-01

    A new type of intelligent CAI system for chemistry is developed in this paper based on automated reasoning with chemistry knowledge.The system has shown its ability to solve chemistry problems,to assist students and teachers in studies and instruction with the automated reasoning functions.Its open mode of the knowledge base and its unique style of the interface between the system and human provide more opportunities for the users to acquire living knowledge through active participation.The automated reasoning based on basic chemistry knowledge also opened a new approach to the information storage and management of the ICAI system for sciences.

  13. The Vibrio cholerae quorum-sensing autoinducer CAI-1: analysis of the biosynthetic enzyme CqsA

    Energy Technology Data Exchange (ETDEWEB)

    Kelly, R.; Bolitho, M; Higgins, D; Lu, W; Ng, W; Jeffrey, P; Rabinowitz, J; Semmelhack, M; Hughson, F; Bassler, B

    2009-01-01

    Vibrio cholerae, the bacterium that causes the disease cholera, controls virulence factor production and biofilm development in response to two extracellular quorum-sensing molecules, called autoinducers. The strongest autoinducer, called CAI-1 (for cholera autoinducer-1), was previously identified as (S)-3-hydroxytridecan-4-one. Biosynthesis of CAI-1 requires the enzyme CqsA. Here, we determine the CqsA reaction mechanism, identify the CqsA substrates as (S)-2-aminobutyrate and decanoyl coenzyme A, and demonstrate that the product of the reaction is 3-aminotridecan-4-one, dubbed amino-CAI-1. CqsA produces amino-CAI-1 by a pyridoxal phosphate-dependent acyl-CoA transferase reaction. Amino-CAI-1 is converted to CAI-1 in a subsequent step via a CqsA-independent mechanism. Consistent with this, we find cells release {ge}100 times more CAI-1 than amino-CAI-1. Nonetheless, V. cholerae responds to amino-CAI-1 as well as CAI-1, whereas other CAI-1 variants do not elicit a quorum-sensing response. Thus, both CAI-1 and amino-CAI-1 have potential as lead molecules in the development of an anticholera treatment.

  14. Heterodimer formation between c-Jun and Jun B proteins mediated by Epstein Barr virus encoded latent membrane protein 1

    Institute of Scientific and Technical Information of China (English)

    SONG Xin; TAO Yongguang; TAN Yunnian; Leo M. Lee; DENG Xiyun; WU Qiao; CAO Ya

    2005-01-01

    Epstein-Barr virus (EBV) encoded latent membrane protein 1 (LMP1) may trigger the transcription factor AP-1 including c-Jun and c-fos. In this report, using a Tet-on LMP1 HNE2 cell line which is a dual-stable LMP1 integrated nasopharyngeal carcinoma (NPC) cell line and the expression of LMP1 in which could be regulated by the Tet-on system, we show that Jun B can efficiently form a new heterodimeric complex with the c-Jun protein under the regulation of LMP1, phosphorylation of c-Jun (ser 63, ser 73) and Jun B is involved in the process of the new heterodimeric formation. We also find that this heterodimeric form can bind to the AP-1 consensus sequence. Transfection studies suggest that JNK interaction protein (JIP) could inhibit the heterodimer formation of c-Jun and Jun B through blocking the AP-1 signaling pathway triggered by LMP1. The interaction and function between c-Jun protein and Jun B protein increase the repertoire of possible regulatory complexes by LMP1 that could play an important role in the regulation of transcription of specific cellular genes in the process of genesis of nasopharyngeal carcinoma.

  15. Structural basis of Na+-independent and cooperative substrate/product antiport in CaiT

    NARCIS (Netherlands)

    Schulze, Sabrina; Köster, Stefan; Geldmacher, Ulrike; Terwisscha van Scheltinga, Anke C.; Kühlbrandt, Werner

    2010-01-01

    Transport of solutes across biological membranes is performed by specialized secondary transport proteins in the lipid bilayer, and is essential for life. Here we report the structures of the sodium-independent carnitine/butyrobetaine antiporter CaiT from Proteus mirabilis (PmCaiT) at 2.3-Å and from

  16. Student Conceptions of, and Attitudes toward, Specific Features of a CAI System.

    Science.gov (United States)

    Hativa, Nira

    1989-01-01

    Describes study of Israeli elementary school students that examined student attitudes toward computer-assisted instruction (CAI) designed to provide drill and practice in arithmetic. Attitudes are compared in relation to students' aptitude, gender, grade level, and socioeconomic status, and implications for the design of CAI systems are discussed.…

  17. Effect of dietary lysine supplement on the performance of Mong Cai sows and their piglets

    NARCIS (Netherlands)

    Pham, K.T.; Duc, le N.; Hendriks, W.H.; Peet-Schwering, van der C.M.C.; Verstegen, M.W.A.

    2010-01-01

    The objective of this study was to determine optimal lysine requirement of lactating Mong Cai sows and their piglets. An experiment was conducted using 30 Mong Cai sows in a factorial randomized design with 5 dietary total lysine levels (0.60, 0.70, 0.85, 1.0 and 1.15%) for one-week pre-partum and 5

  18. CAI, Lecture, and Student Learning Style: The Differential Effects of Instructional Method.

    Science.gov (United States)

    Ester, Don P.

    1995-01-01

    Describes a study that compared the effectiveness of computer-assisted instruction (CAI) and lecture approaches in teaching vocal anatomy and function to 60 undergraduate music students with different learning styles. Highlights include background on learning styles, implications for the use of CAI with various learning styles, and recommendations…

  19. Structural basis of Na+-independent and cooperative substrate/product antiport in CaiT

    NARCIS (Netherlands)

    Schulze, Sabrina; Köster, Stefan; Geldmacher, Ulrike; Terwisscha van Scheltinga, Anke C.; Kühlbrandt, Werner

    2010-01-01

    Transport of solutes across biological membranes is performed by specialized secondary transport proteins in the lipid bilayer, and is essential for life. Here we report the structures of the sodium-independent carnitine/butyrobetaine antiporter CaiT from Proteus mirabilis (PmCaiT) at 2.3-Å and from

  20. The Graphics Terminal Display System; a Powerful General-Purpose CAI Package.

    Science.gov (United States)

    Hornbeck, Frederick W., Brock, Lynn

    The Graphic Terminal Display System (GTDS) was created to support research and development in computer-assisted instruction (CAI). The system uses an IBM 360/50 computer and interfaces with a large-screen graphics display terminal, a random-access slide projector, and a speech synthesizer. An authoring language, GRAIL, was developed for CAI, and…

  1. A Study of Effectiveness of Computer Assisted Instruction (CAI) over Classroom Lecture (CRL) at ICS Level

    Science.gov (United States)

    Kaousar, Tayyeba; Choudhry, Bushra Naoreen; Gujjar, Aijaz Ahmed

    2008-01-01

    This study was aimed to evaluate the effectiveness of CAI vs. classroom lecture for computer science at ICS level. The objectives were to compare the learning effects of two groups with classroom lecture and computer-assisted instruction studying the same curriculum and the effects of CAI and CRL in terms of cognitive development. Hypotheses of…

  2. CAI - There Is a Way to Make It Pay (But Not in Conventional Schooling)

    Science.gov (United States)

    Butman, Robert C.

    1973-01-01

    CAI can pay by choosing a market where a decrease in training time or an increase in student-teacher ratios can be translated into lower over-all costs to the system. This situation obtains when CAI is used for the education and training of professionals, children with learning disabilities and others whose instructional needs cannot be met by the…

  3. Brief Introduction to the Foundation of CAI Shidong Award for Plasma Physics

    Institute of Scientific and Technical Information of China (English)

    SHENG Zhengming

    2010-01-01

    @@ The late Academician Professor CAI Shidong was an outstanding plasma physicist who had made seminal contributions in both fundamental plasma theories and controlled thermonuclear fusion energy research.Professor CAI was also one of the pioneers in China's plasma physics research.In 1973,Professor CAI decided to leave U.S.and return to China in order to help pushing forward plasma physics research in China.Professor CAI formed a research group consisting of young scientists and carried out high-level works in this important physics discipline.He worked tirelessly,set examples by his own deeds,and made outstanding contributions in plasma physics research,educating younger generations of plasma physicists,as well as establishing collaborations with plasma scientists in other Asian-African developing nations.In short,Professor CAI devoted the best years of his life to China's plasma physics research.

  4. Temporal and spatial expression of c-jun and jun-B proto-oncogenes in pulp cells involved with reparative dentinogenesis after cavity preparation of rat molars.

    Science.gov (United States)

    Kitamura, C; Kimura, K; Nakayama, T; Terashita, M

    1999-02-01

    c-jun and jun-B are nuclear proto-oncogenes induced by growth factors such as bone morphogenetic proteins (BMPs). These gene products enhance the expression of many genes, including osteocalcin and collagen types, indicating that c-jun and jun-B play important roles in the cell differentiation process. It is also known that BMPs affect the differentiation of pulp cells to odontoblast-like cells during reparative dentinogenesis, but little is known about the transcriptional regulation of genes in cells associated with reparative dentinogenesis. In this study, we examined the expression of c-jun and jun-B in pulp cells during reparative dentinogenesis after cavity preparation of rat molars by in situ hybridization. In rat tooth germs, c-jun and jun-B were co-expressed in the odontoblastic lineage. In rat adult molars, c-jun was expressed in the odontoblast layer, but the jun-B expression was absent in all pulp cells. After cavity preparation, we found that c-jun and jun-B were coexpressed in pulp cells underneath cavities. During the early phase of reparative dentinogenesis, levels of c-jun and jun-B greatly increased in pulp cells within and around the reparative dentin matrix formed adjacent to the cavity floor. Fourteen days after cavity preparation, c-jun and jun-B were expressed only in pulp cells lining the irregular surface of the thick reparative dentin. These results suggest that c-jun and jun-B may play important roles both in physiological and in reparative dentinogenesis; in particular, the limited distribution of the jun-B expression suggests a specific role of jun-B only in cells involved with the active formation of the dentin matrix during primary and reparative dentinogenesis.

  5. Personality preference influences medical student use of specific computer-aided instruction (CAI

    Directory of Open Access Journals (Sweden)

    Halsey Martha

    2006-02-01

    Full Text Available Abstract Background The objective of this study was to test the hypothesis that personality preference, which can be related to learning style, influences individual utilization of CAI applications developed specifically for the undergraduate medical curriculum. Methods Personality preferences of students were obtained using the Myers-Briggs Type Indicator (MBTI test. CAI utilization for individual students was collected from entry logs for two different web-based applications (a discussion forum and a tutorial used in the basic science course on human anatomy. Individual login data were sorted by personality preference and the data statistically analyzed by 2-way mixed ANOVA and correlation. Results There was a wide discrepancy in the level and pattern of student use of both CAI. Although individual use of both CAI was positively correlated irrespective of MBTI preference, students with a "Sensing" preference tended to use both CAI applications more than the "iNtuitives". Differences in the level of use of these CAI applications (i.e., higher use of discussion forum vs. a tutorial were also found for the "Perceiving/Judging" dimension. Conclusion We conclude that personality/learning preferences of individual students influence their use of CAI in the medical curriculum.

  6. CAD/CAM/CAI Application for High-Precision Machining of Internal Combustion Engine Pistons

    Directory of Open Access Journals (Sweden)

    V. V. Postnov

    2014-07-01

    Full Text Available CAD/CAM/CAI application solutions for internal combustion engine pistons machining was analyzed. Low-volume technology of internal combustion engine pistons production was proposed. Fixture for CNC turning center was designed.

  7. 77 FR 9625 - Presentation of Final Conventional Conformance Test Criteria and Common Air Interface (CAI...

    Science.gov (United States)

    2012-02-17

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF COMMERCE National Institute of Standards and Technology Presentation of Final Conventional Conformance Test Criteria and Common Air Interface (CAI) Features/Functionalities Under Test in the Project 25...

  8. Performance and analysis of a 4-stroke multi-cylinder gasoline engine with CAI combustion

    OpenAIRE

    Zhao, H.; Li, J; Ma, T.; Ladommatos, N

    2002-01-01

    Copyright © 2002 SAE International. This paper is posted on this site with permission from SAE International. Further use of this paper is not permitted without permission from SAE Controlled Auto-Ignition (CAI) combustion was realised in a production type 4-stroke 4-cylinder gasoline engine without intake charge heating or increasing compression ratio. The CAI engine operation was achieved using substantially standard components modified only in camshafts to restrict the gas exchange proc...

  9. Formation of refractory metal nuggets and their link to the history of CAIs

    Science.gov (United States)

    Schwander, D.; Kööp, L.; Berg, T.; Schönhense, G.; Heck, P. R.; Davis, A. M.; Ott, U.

    2015-11-01

    Ca, Al-rich inclusions (CAIs) often contain numerous refractory metal nuggets (RMNs), consisting of elements like Os, Ir, Mo, Pt and Ru. The nuggets are usually thought to have formed by equilibrium condensation from a gas of solar composition, simultaneously with or prior to oxide and silicate minerals. However, the exact mechanisms responsible for their extremely variable compositions, small sizes and associations with CAI minerals remain puzzling. Expanding on previous work on chemically separated RMNs, we have studied a large number of RMNs within their host CAIs from three different meteorite types, i.e., the highly primitive chondrite Acfer 094 (C2-ungrouped), Allende (CV3ox) and Murchison (CM2). Our results show several inconsistencies between the observed features and a direct condensation origin, including a lack of correlated abundance variations in the refractory metals that are expected from variations in condensation temperature. Instead, we show that most RMN features are consistent with RMN formation by precipitation from a CAI liquid enriched in refractory metals. This scenario is additionally supported by the common occurrence of RMNs in CAIs with clear melt crystallization textures as well as the occurrence of synthetic RMNs with highly variable compositions in run products from Schwander et al. (2015). In some cases, the sizes of meteoritic RMNs correlate with the sizes of their host minerals in CAIs, which indicates common cooling rates.

  10. The Effect of the Computer Assisted Instruction (CAI on Student Attitude in Mathematics Teaching of Primary School 8th Class and Views of Students towards CAI

    Directory of Open Access Journals (Sweden)

    Tuğba Hangül

    2010-12-01

    Full Text Available The aim of this study is to research the effect of the subject of “Geometric Objects” which is included in mathematics curriculum at the eighth grade on the student attitude using computer assisted instruction (CAI and find out grade 8 primary school students’ views about the computer-assisted instruction. In this study the pre-post attitude with experimental control group design was performed. The research was done under control and experiment groups consisting of fifty-three eighth grade students who were randomly identified in the year of 2009-2010. Attitude was applied to the both groups before and at the end of teaching. The method of constructivism was applied to control the group while CAI was applied to the experiment group. After teaching, fourteen students who were randomly selected from the experimental group were interviewed. Quantitative data was analyzed using Independent Samples t-test and qualitative data was analyzed by description analyze. At the end of the study, the data put forward that teaching through CAI improves the students’ attitudes positively than the method of Constructivism and students have positive opinions on CAI.

  11. Effects of Computer-Assisted Instruction (CAI) on 11th Graders' Attitudes to Biology and CAI and Understanding of Reproduction in Plants and Animals.

    Science.gov (United States)

    Soyibo, Kola; Hudson, Ann

    2000-01-01

    Investigates whether the use of the combination of lecture, discussion, and computer-assisted instruction (CAI) significantly improved students' attitudes toward biology and their understanding of reproduction in plants and animals. Studies grade 11 Jamaican female students (n=77) from two traditional high schools in Kingston. (Contains 19…

  12. c-Jun transactivates Puma gene expression to promote osteoarthritis.

    Science.gov (United States)

    Lu, Huading; Hou, Gang; Zhang, Yongkai; Dai, Yuhu; Zhao, Huiqing

    2014-05-01

    Osteoarthritis (OA) is a chronic degenerative joint disorder in which genetic, hormonal, mechanical and ageing factors affect its progression. Current studies are focusing on chondrocytes as a key mediator of OA at a cellular level. however, the mechanism underlying chondrocyte apoptosis remains unclear. PUMA is a pro-apoptotic member of the BH3-only subgroup of the Bcl-2 family and is involved in a large number of physiological and pathological processes. In the present study, we examined whether PUMA has a role in IL-1β-induced apoptosis and whether the c-Jun N-terminal kinase (JNK)/c-Jun pathway mediates the induction of PUMA, thus contributing to chondrocyte apoptosis. The results demonstrated an increase in PUMA protein and mRNA levels in cultured mouse chondrocytes following 4 h of IL-1β treatment. Furthermore, this upregulation of PUMA was critical for chondrocyte apoptosis as knockdown of PUMA using PUMA-specific siRNA significantly reduced apoptosis in cultured cells. Upon pharmacological inhibition of the JNK/c-Jun pathway with CE11004 or SP600125, the expression of PUMA was notably suppressed with a concomitant decrease in apoptosis observed in IL-1β-treated chondrocytes. Also, immunohistochemical studies revealed that the PUMA and c-Jun proteins were upregulated in chondrocytes from the articular cartilage of OA patients. Together, these data suggest a role for PUMA and the JNK/c-Jun pathway in the regulation of chondrocyte apoptosis during OA.

  13. Fine-Gained CAIs in Comet Samples: Moderate Refractory Character and Comparison to Small Refractory Inclusions in Chondrites

    Science.gov (United States)

    Joswiak, D. J.; Brownlee, D. E.; Nguyen, A. N.; Messenger, S

    2017-01-01

    Examination of >200 comet Wild 2 particles collected by the Stardust (SD) mission shows that the CAI abundance of comet Wild 2's rocky material is near 1% and that nearly 50% of all bulbous tracks will contain at least one recognizable CAI fragment. A similar abundance to Wild 2 is found in a giant cluster IDP thought to be of cometary origin. The properties of these CAIs and their comparison with meteoritic CAIs provide important clues on the role of CAIs in the early Solar System (SS) and how they were transported to the edge of the solar nebula where Kuiper Belt comets formed. Previously, only two CAIs in comet Wild 2 had been identified and studied in detail. Here we present 2 new Wild 2 CAIs and 2 from a giant cluster cometary IDP, describe their mineralogical characteristics and show that they are most analogous to nodules in spinel-rich, fine-grained inclusions (FGIs) observed in CV3 and other chondrites. Additionally, we present new O isotope measurements from one CAI from comet Wild 2 and show that its oxygen isotopic composition is similar to some FGIs. This is only the second CAI from Wild 2 in which O isotopes have been measured.

  14. The role of dye affinity in optical measurements of Cai(2+) transients in cardiac muscle.

    Science.gov (United States)

    Kong, Wei; Fast, Vladimir G

    2014-07-01

    Previous experiments in cultures of neonatal rat myocytes demonstrated that the shape of Cai(2+) transients measured using high-affinity Ca(2+)-sensitive dyes may be misrepresented. The purpose of this study was to examine the role of dye affinity in Cai(2+) measurements in intact adult cardiac tissue by comparing optical recordings obtained with high- and low-affinity dyes. Experiments were carried out in porcine left ventricular (LV) wedge preparations stained locally by intramural injection via microcapillaries (diameter = 150 μm) with a low-affinity Ca(2+)-sensitive dye Fluo-4FF or Fluo-2LA (nominal Kd, ~7-10 μmol/l), high-affinity dye Rhod-2 (Kd = 0.57 μmol/l), and Fluo-4 or Fluo-2MA (Kd, ~0.4 μmol/l); in addition, tissue was stained with transmembrane potential (Vm)-sensitive dye RH-237. Optical recordings of Vm and Cai(2+) were made using optical fibers (diameter = 325 μm) glued with the microcapillaries. The durations of Cai(2+) transients measured at 50% level of recovery (CaD50) using high-affinity Fluo-4/Fluo-2MA dyes were up to ~81% longer than those measured with low-affinity Fluo-4FF/Fluo-2LA at long pacing cycle lengths (CL). In Fluo-4/Fluo-2MA measurements at long CLs, Cai(2+) transients often (~50% of cases) exhibited slow upstroke rise and extended plateau. In Rhod-2 measurements, CaD50 was moderately longer (up to ~35%) than in Fluo-4FF recordings, but Cai(2+) transient shapes were similar. In all series of measurements, mean action potential duration values were not significantly different (P > 0.05). The delays between Vm and Cai(2+) upstrokes were comparable for low- and high-affinity dyes (P > 0.05). In conclusion, measurements of Cai(2+) transient in ventricular myocardium are strongly affected by the affinity of Ca(2+) dyes. The high-affinity dyes may overestimate the duration and alter the shape of Cai(2+) transients. Copyright © 2014 the American Physiological Society.

  15. The role of dye affinity in optical measurements of Cai2+ transients in cardiac muscle

    Science.gov (United States)

    Kong, Wei

    2014-01-01

    Previous experiments in cultures of neonatal rat myocytes demonstrated that the shape of Cai2+ transients measured using high-affinity Ca2+-sensitive dyes may be misrepresented. The purpose of this study was to examine the role of dye affinity in Cai2+ measurements in intact adult cardiac tissue by comparing optical recordings obtained with high- and low-affinity dyes. Experiments were carried out in porcine left ventricular (LV) wedge preparations stained locally by intramural injection via microcapillaries (diameter = 150 μm) with a low-affinity Ca2+-sensitive dye Fluo-4FF or Fluo-2LA (nominal Kd, ∼7–10 μmol/l), high-affinity dye Rhod-2 (Kd = 0.57 μmol/l), and Fluo-4 or Fluo-2MA (Kd, ∼0.4 μmol/l); in addition, tissue was stained with transmembrane potential (Vm)-sensitive dye RH-237. Optical recordings of Vm and Cai2+ were made using optical fibers (diameter = 325 μm) glued with the microcapillaries. The durations of Cai2+ transients measured at 50% level of recovery (CaD50) using high-affinity Fluo-4/Fluo-2MA dyes were up to ∼81% longer than those measured with low-affinity Fluo-4FF/Fluo-2LA at long pacing cycle lengths (CL). In Fluo-4/Fluo-2MA measurements at long CLs, Cai2+ transients often (∼50% of cases) exhibited slow upstroke rise and extended plateau. In Rhod-2 measurements, CaD50 was moderately longer (up to ∼35%) than in Fluo-4FF recordings, but Cai2+ transient shapes were similar. In all series of measurements, mean action potential duration values were not significantly different (P > 0.05). The delays between Vm and Cai2+ upstrokes were comparable for low- and high-affinity dyes (P > 0.05). In conclusion, measurements of Cai2+ transient in ventricular myocardium are strongly affected by the affinity of Ca2+ dyes. The high-affinity dyes may overestimate the duration and alter the shape of Cai2+ transients. PMID:24791783

  16. Mineralogy and Petrology of EK-459-5-1, A Type B1 CAI from Allende

    Science.gov (United States)

    Jeffcoat, C. R.; Kerekgyarto, A. G.; Lapen, T. J.; Andreasen, R.; Righter, M.; Ross, D. K.

    2015-01-01

    Calcium-aluminum-rich inclusions (CAIs) are a type of coarse-grained clast composed of Ca-, Al-, and Mg-rich silicates and oxides found in chondrite meteorites. Type B (CAIs) are exclusively found in the CV chondrite meteorites and are the most well studied type of inclusion found in chondritic meteorites. Type B1 CAIs are distinguished by a nearly monomineralic rim of melilite that surrounds an interior predominantly composed of melilite, fassaite (Ti and Al-rich clinopyroxene), anorthite, and spinel with varying amounts of other minor primary and secondary phases. The formation of Type B CAIs has received considerable attention in the course of CAI research and quantitative models, experimental results and observations from Type B inclusions remain largely in disagreement. Recent experimental results and quantitative models have shown that the formation of B1 mantles could have occurred by the evaporative loss of Si and Mg during the crystallization of these objects. However, comparative studies suggest that the lower bulk SiO2 compositions in B1s result in more prior melilite crystallization before the onset of fassaite and anorthite crystallization leading to the formation of thick melilite rich rims in B1 inclusions. Detailed petrographic and cosmochemical studies of these inclusions will further our understanding of these complex objects.

  17. THERMAL HISTORY OF THE CARNIC ALPS (NE ITALY-S. AUSTRIA USING CAI ANALYSIS

    Directory of Open Access Journals (Sweden)

    MONICA PONDRELLI

    2002-11-01

    Full Text Available Thermal patterns of an area which underwent a polyphase deformation history such as the Carnic Alps were analyzed using the Colour Alteration Index (CAI of conodonts in order to constrain some aspects of the metamorphic history of this part of the Southern Alps. Hercynian and alpine tectonothermal events were distinguished using CAI analysis.  The Hercynian event developed temperatures up to low metamorphic conditions. Alpine tectonogenesis did not produce thermal levels in excess of the diagenetic zone. Moreover, CAI patterns allow recognition and evaluation of a hydrothermal metamorphic overprint of Permo-Triassic or Oligocene age that was superimposed on the pre-existing regional metamorphic zonation.   

  18. Arginine oscillation explains Na+ independence in the substrate/product antiporter CaiT.

    Science.gov (United States)

    Kalayil, Sissy; Schulze, Sabrina; Kühlbrandt, Werner

    2013-10-22

    Most secondary-active transporters transport their substrates using an electrochemical ion gradient. In contrast, the carnitine transporter (CaiT) is an ion-independent, l-carnitine/γ-butyrobetaine antiporter belonging to the betaine/carnitine/choline transporter family of secondary transporters. Recently determined crystal structures of CaiT from Escherichia coli and Proteus mirabilis revealed an inverted five-transmembrane-helix repeat similar to that in the amino acid/Na(+) symporter LeuT. The ion independence of CaiT makes it unique in this family. Here we show that mutations of arginine 262 (R262) make CaiT Na(+)-dependent. The transport activity of R262 mutants increased by 30-40% in the presence of a membrane potential, indicating substrate/Na(+) cotransport. Structural and biochemical characterization revealed that R262 plays a crucial role in substrate binding by stabilizing the partly unwound TM1' helix. Modeling CaiT from P. mirabilis in the outward-open and closed states on the corresponding structures of the related symporter BetP reveals alternating orientations of the buried R262 sidechain, which mimic sodium binding and unbinding in the Na(+)-coupled substrate symporters. We propose that a similar mechanism is operative in other Na(+)/H(+)-independent transporters, in which a positively charged amino acid replaces the cotransported cation. The oscillation of the R262 sidechain in CaiT indicates how a positive charge triggers the change between outward-open and inward-open conformations as a unifying critical step in LeuT-type transporters.

  19. Military Standard Common APSE (Ada Programming Support Environment) Interface Set (CAIS).

    Science.gov (United States)

    1985-01-01

    Package FILE-IMPORT.EXPORT The CAIS allows a particula : CAIS implementation to maintain fies separately from nle maintained by the host file system. This...function EXACT(LrST : in LIST TYPE; NANO : in TOKEN TYPE) return NUWDER; 207 PROPO’ FP MtL-S.TD-C jJS 31 JNNIARIY 19W.% Purpose: This function locates...NAME STRING) RESULT: LIST TEXT(1., 10); begin null; -- should be defined by Implementor end DELETE; procedure DELETECLIST: in out LISTTYPE; NANO

  20. On native Danish learners' challenges in distinguishing /tai/, /cai/ and /zai/

    DEFF Research Database (Denmark)

    Sloos, Marjoleine; Zhang, Chun

    2015-01-01

    Chinese (L2) initial consonants, namely , phonologically /th ts tsh/. Impressionistically, disentangling tai-cai-zai is extremely challenging for Danish learners, but experimental confirmation is lacking (Wang, Sloos & Zhang 2015, forthcoming). Eighteen native Danish learners of Chinese of Aarhus...... University participated in an ABX experiment. They were auditorily presented pairs of the critical stimuli tai-cai-zai, te-ce-ze and tuo-cuo-zuo combined with all four tones and alternated with fillers. The subjects indicated for each pair which of the two words matched the pinyin description. The expected...

  1. Germination of white radish, buckwheat and qing-geng-cai under low pressure in closed environment.

    Science.gov (United States)

    Hinokuchi, Tsutomu; Oshima, Satoshi; Hashimoto, Hirofumi

    2004-11-01

    In order to cultivate plants under low pressure in closed environment, the germination rate of seeds of white radish was investigated under low pressure, low oxygen partial pressure and condition of pure oxygen. The result of these experiments showed that the germination rate was affected by the oxygen partial pressure. From this fact, it is possible to lower the total pressure by using only the pure oxygen in germination. Furthermore, the germination rates of seeds of buckwheat and qing-geng-cai were also investigated in pure oxygen for the comparison. Consequently, though tendency in germination rate of white radish was similar to qing-geng-cai, it was different from buckwheat.

  2. 人物专栏:马军%Personage Column: MA Jun

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    @@ Ma Jun is the Head of Harbin Institute of Hematology & Oncology that serves as a teaching, research and medical center of hematology and oncology in China. Dr. Ma is a very famous professor of Hematology and Oncology in the county and abroad now.

  3. Thermal and chemical evolution in the early solar system as recorded by FUN CAIs: Part I - Petrology, mineral chemistry, and isotopic composition of Allende FUN CAI CMS-1

    Science.gov (United States)

    Williams, C. D.; Ushikubo, T.; Bullock, E. S.; Janney, P. E.; Hines, R. R.; Kita, N. T.; Hervig, R. L.; MacPherson, G. J.; Mendybaev, R. A.; Richter, F. M.; Wadhwa, M.

    2017-03-01

    Detailed petrologic, geochemical and isotopic analyses of a new FUN CAI from the Allende CV3 meteorite (designated CMS-1) indicate that it formed by extensive melting and evaporation of primitive precursor material(s). The precursor material(s) condensed in a 16O-rich region (δ17O and δ18O ∼ -49‰) of the inner solar nebula dominated by gas of solar composition at total pressures of ∼10-3-10-6 bar. Subsequent melting of the precursor material(s) was accompanied by evaporative loss of magnesium, silicon and oxygen resulting in large mass-dependent isotope fractionations in these elements (δ25Mg = 30.71-39.26‰, δ29Si = 14.98-16.65‰, and δ18O = -41.57 to -15.50‰). This evaporative loss resulted in a bulk composition similar to that of compact Type A and Type B CAIs, but very distinct from the composition of the original precursor condensate(s). Kinetic fractionation factors and the measured mass-dependent fractionation of silicon and magnesium in CMS-1 suggest that ∼80% of the silicon and ∼85% of the magnesium were lost from its precursor material(s) through evaporative processes. These results suggest that the precursor material(s) of normal and FUN CAIs condensed in similar environments, but subsequently evolved under vastly different conditions such as total gas pressure. The chemical and isotopic differences between normal and FUN CAIs could be explained by sorting of early solar system materials into distinct physical and chemical regimes, in conjunction with discrete heating events, within the protoplanetary disk.

  4. CAI and the Development of Automaticity in Mathematics Skills in Students with and without Mild Mental Handicaps.

    Science.gov (United States)

    Lin, Agnes; And Others

    1994-01-01

    Describes a study that compared computer-assisted instruction (CAI) and a more traditional paper-and-pencil method in teaching mathematics skills to elementary school students with and without mild mental handicaps. Pretests and posttests were analyzed, and it was found that CAI, and extended practice, enhanced automatization of mathematics…

  5. Gender Role, Gender Identity and Sexual Orientation in CAIS ("XY-Women") Compared With Subfertile and Infertile 46,XX Women.

    Science.gov (United States)

    Brunner, Franziska; Fliegner, Maike; Krupp, Kerstin; Rall, Katharina; Brucker, Sara; Richter-Appelt, Hertha

    2016-01-01

    The perception of gender development of individuals with complete androgen insensitivity syndrome (CAIS) as unambiguously female has recently been challenged in both qualitative data and case reports of male gender identity. The aim of the mixed-method study presented was to examine the self-perception of CAIS individuals regarding different aspects of gender and to identify commonalities and differences in comparison with subfertile and infertile XX-chromosomal women with diagnoses of Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) and polycystic ovary syndrome (PCOS). The study sample comprised 11 participants with CAIS, 49 with MRKHS, and 55 with PCOS. Gender identity was assessed by means of a multidimensional instrument, which showed significant differences between the CAIS group and the XX-chromosomal women. Other-than-female gender roles and neither-female-nor-male sexes/genders were reported only by individuals with CAIS. The percentage with a not exclusively androphile sexual orientation was unexceptionally high in the CAIS group compared to the prevalence in "normative" women and the clinical groups. The findings support the assumption made by Meyer-Bahlburg ( 2010 ) that gender outcome in people with CAIS is more variable than generally stated. Parents and professionals should thus be open to courses of gender development other than typically female in individuals with CAIS.

  6. Stable Magnesium Isotope Variation in Melilite Mantle of Allende Type B1 CAI EK 459-5-1

    Science.gov (United States)

    Kerekgyarto, A. G.; Jeffcoat, C. R.; Lapen, T. J.; Andreasen, R.; Righter, M.; Ross, D. K.

    2014-01-01

    Ca-Al-rich inclusions (CAIs) are the earliest formed crystalline material in our solar system and they record early Solar System processes. Here we present petrographic and delta Mg-25 data of melilite mantles in a Type B1 CAI that records early solar nebular processes.

  7. The Matriculation Science Curriculum of the USM in the Context of the PPI and CAI Modes of Instruction.

    Science.gov (United States)

    Cheng, Chuah Chong; Seng, Chin Pin

    1985-01-01

    Discusses philosophy, aims and objectives, and structure of the Matriculation Science Curriculum of the University Sains Malaysia. Includes comments on instructional strategies, individualized learning, programmed instruction, systems approach to computer-assisted instruction (CAI) implementation, CAI authoring system, and various program…

  8. Revision of the Oriental leafhopper genus Destinoides Cai & He (Hemiptera: Cicadellidae: Ledrinae), with a new synonym and two new combinations.

    Science.gov (United States)

    Sun, Jing; Webb, Michael D; Zhang, Yalin

    2014-01-01

    The leafhopper genus Destinoides Cai & He is revised to include two species D. latifrons (Walker 1851, Ledra) n. comb. and D. conspicuus (Distant 1907, Petalocephala) n. comb. Destinoides fasciata Cai & He, 2000 is placed as a junior synonym of D. latifrons, syn. nov. These two species are redescribed and illustrated in detail and a key is given based on the males.

  9. File list: Oth.Bld.05.JUN.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Bld.05.JUN.AllCell hg19 TFs and others JUN Blood SRX150681,SRX186614,SRX150600,...SRX150546,SRX015140,SRX150491,SRX150547 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Bld.05.JUN.AllCell.bed ...

  10. File list: Oth.Brs.05.JUN.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Brs.05.JUN.AllCell hg19 TFs and others JUN Breast SRX883585,SRX883584,SRX268299...,SRX1044413,SRX1044412,SRX1044411,SRX1142763,SRX1142761,SRX039141,SRX039142 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Brs.05.JUN.AllCell.bed ...

  11. File list: Oth.Bld.10.JUN.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Bld.10.JUN.AllCell hg19 TFs and others JUN Blood SRX150681,SRX150600,SRX186614,...SRX015140,SRX150491,SRX150546,SRX150547 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Bld.10.JUN.AllCell.bed ...

  12. File list: Oth.Bld.50.JUN.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Bld.50.JUN.AllCell hg19 TFs and others JUN Blood SRX150681,SRX150546,SRX186614,...SRX150491,SRX015140,SRX150547,SRX150600 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Bld.50.JUN.AllCell.bed ...

  13. File list: Oth.Brs.50.JUN.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Brs.50.JUN.AllCell hg19 TFs and others JUN Breast SRX883584,SRX883585,SRX114276...1,SRX268299,SRX1044413,SRX1044412,SRX1044411,SRX1142763,SRX039142,SRX039141 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Brs.50.JUN.AllCell.bed ...

  14. File list: Oth.Brs.10.JUN.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Brs.10.JUN.AllCell hg19 TFs and others JUN Breast SRX883585,SRX268299,SRX883584...,SRX1044413,SRX1044412,SRX1142763,SRX1142761,SRX1044411,SRX039142,SRX039141 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Brs.10.JUN.AllCell.bed ...

  15. File list: Oth.Myo.20.Jun.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Myo.20.Jun.AllCell mm9 TFs and others Jun Muscle SRX497491,SRX497490,SRX155449,...SRX155448 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Myo.20.Jun.AllCell.bed ...

  16. File list: Oth.Myo.05.Jun.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Myo.05.Jun.AllCell mm9 TFs and others Jun Muscle SRX497491,SRX497490,SRX155449,...SRX155448 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Myo.05.Jun.AllCell.bed ...

  17. File list: Oth.Myo.50.Jun.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Myo.50.Jun.AllCell mm9 TFs and others Jun Muscle SRX497491,SRX497490,SRX155449,...SRX155448 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Myo.50.Jun.AllCell.bed ...

  18. File list: Oth.ALL.20.Jun.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.ALL.20.Jun.AllCell mm9 TFs and others Jun All cell types SRX172346,SRX172331,SR...,SRX848544,SRX848542,SRX155448 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.ALL.20.Jun.AllCell.bed ...

  19. File list: Oth.Myo.10.Jun.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Myo.10.Jun.AllCell mm9 TFs and others Jun Muscle SRX497491,SRX497490,SRX155449,...SRX155448 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Myo.10.Jun.AllCell.bed ...

  20. File list: Oth.Bld.20.Jun.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Bld.20.Jun.AllCell mm9 TFs and others Jun Blood SRX172346,SRX172331,SRX140364,S...RX096389,SRX172330,SRX437449,SRX172336,SRX096388 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Bld.20.Jun.AllCell.bed ...

  1. File list: Oth.Bld.10.Jun.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Bld.10.Jun.AllCell mm9 TFs and others Jun Blood SRX140364,SRX172346,SRX172331,S...RX437449,SRX096389,SRX096388,SRX172336,SRX172330 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Bld.10.Jun.AllCell.bed ...

  2. File list: Oth.ALL.50.Jun.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.ALL.50.Jun.AllCell mm9 TFs and others Jun All cell types SRX172346,SRX497491,SR...,SRX155448,SRX848542,SRX172336 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.ALL.50.Jun.AllCell.bed ...

  3. File list: Oth.Bld.05.Jun.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Bld.05.Jun.AllCell mm9 TFs and others Jun Blood SRX140364,SRX172346,SRX172331,S...RX096388,SRX096389,SRX437449,SRX172336,SRX172330 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Bld.05.Jun.AllCell.bed ...

  4. File list: Oth.ALL.10.Jun.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.ALL.10.Jun.AllCell mm9 TFs and others Jun All cell types SRX140364,SRX172346,SR...SRX1431656,SRX848544,SRX172330 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.ALL.10.Jun.AllCell.bed ...

  5. File list: Oth.Bld.50.Jun.AllCell [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Bld.50.Jun.AllCell mm9 TFs and others Jun Blood SRX172346,SRX140364,SRX096389,S...RX172331,SRX172330,SRX437449,SRX096388,SRX172336 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Bld.50.Jun.AllCell.bed ...

  6. Evaluation of Title I CAI Programs at Minnesota State Correctional Institutions.

    Science.gov (United States)

    Sandman, Richard S.; Welch, Wayne W.

    Three Minnesota correctional institutions used computer-assisted instruction (CAI) on PLATO terminals to improve reading and mathematics skills: (1) the State Reformatory for Men, St. Cloud (males, ages 17-21); (2) the Minnesota Home School, Sauk Centre (males and females, ages 12-18); and (3) the State Training School, Red Wing (males, ages…

  7. Socioeconomic Status, Aptitude, and Gender Differences in CAI Gains of Arithmetic.

    Science.gov (United States)

    Hativa, Nira; Shorer, Dvora

    1989-01-01

    A report is given of a study which examined the effects of computer-assisted instruction (CAI) in mathematics on 99 disadvantaged and 112 advantaged Israeli students. Higher performance levels and larger gains were found for advantaged over disadvantaged students, for high achievers over low achievers, and for boys over girls. (IAH)

  8. Real-Time Graphics for CAI: A Rudimentary Grammar and Demonstration Program.

    Science.gov (United States)

    Winn, William

    This paper focuses on graphics and how they can be created, in real time, from information stored in a database, and the application of this technique to computer-assisted instruction (CAI). It is noted that this is a special case of the general trend towards endowing instructional systems with a degree of decision-making or design expertise, as…

  9. CAIS/ACSI 2001: Beyond the Web: Technologies, Knowledge and People.

    Science.gov (United States)

    Canadian Journal of Information and Library Science, 2000

    2000-01-01

    Presents abstracts of papers presented at the 29th Annual Conference of the Canadian Association for Information Science (CAIS) held in Quebec on May 27-29, 2001. Topics include: professional development; librarian/library roles; information technology uses; virtual libraries; information seeking behavior; literacy; information retrieval;…

  10. Calcium-aluminum-rich inclusions with fractionation and unknown nuclear effects (FUN CAIs)

    DEFF Research Database (Denmark)

    Krot, Alexander N.; Nagashima, Kazuhide; Wasserburg, Gerald J.

    2014-01-01

    We present a detailed characterization of the mineralogy, petrology, and oxygen isotopic compositions of twelve FUN CAIs, including C1 and EK1-4-1 from Allende (CV), that were previously shown to have large isotopic fractionation patterns for magnesium and oxygen, and large isotopic anomalies of ...

  11. Effectiveness of Computer Assisted Instructions (CAI) in Teaching of Mathematics at Secondary Level

    Science.gov (United States)

    Dhevakrishnan, R.; Devi, S.; Chinnaiyan, K.

    2012-09-01

    The present study was aimed at effectiveness of computer assisted instructions (CAI) in teaching of mathematics at secondary level adopted experimental method and observing the difference between (CAI) and traditional method. A sample of sixty (60) students of IX class in VVB Matriculation Higher Secondary School at Elayampalayam, Namakkal district were selected for a sample and sample was divided into two group namely experiment and control group. The experimental group consisted 30 students who were taught 'Mensurationí by the computer assisted instructions and the control groups comprising 30 students were taught by the conventional method of teaching. Data analyzed using mean, S.D. and t-test. Findings of the study clearly point out that significant increase in the mean gain scores has been found in the post test scores of the experimental group. Significant differences have been found between the control group and experimental group on post test gain scores. The experiment group, which was taught by the CAI showed better, learning. The conclusion is evident that the CAI is an effective media of instruction for teaching Mathematics at secondary students.s

  12. Consumption of fa cai Nostoc soup: a potential for BMAA exposure from Nostoc cyanobacteria in China?

    Science.gov (United States)

    Roney, Britton R; Renhui, Li; Banack, Sandra Anne; Murch, Susan; Honegger, Rosmarie; Cox, Paul Alan

    2009-01-01

    Grown in arid regions of western China the cyanobacterium Nostoc flagelliforme--called fa cai in Mandarin and fat choy in Cantonese--is wild-harvested and used to make soup consumed during New Year's celebrations. High prices, up to $125 USD/kg, led to overharvesting in Inner Mongolia, Ningxia, Gansu, Qinghai, and Xinjiang. Degradation of arid ecosystems, desertification, and conflicts between Nostoc harvesters and Mongol herdsmen concerned the Chinese environmental authorities, leading to a government ban of Nostoc commerce. This ban stimulated increased marketing of a substitute made from starch. We analysed samples purchased throughout China as well as in Chinese markets in the United States and the United Kingdom. Some were counterfeits consisting of dyed starch noodles. A few samples from California contained Nostoc flagelliforme but were adulterated with starch noodles. Other samples, including those from the United Kingdom, consisted of pure Nostoc flagelliforme. A recent survey of markets in Cheng Du showed no real Nostoc flagelliforme to be marketed. Real and artificial fa cai differ in the presence of beta-N-methylamino-L-alanine (BMAA). Given its status as a high-priced luxury food, the government ban on collection and marketing, and the replacement of real fa cai with starch substitutes consumed only on special occasions, it is anticipated that dietary exposure to BMAA from fa cai will be reduced in the future in China.

  13. Using CAI To Enhance the Peer Acceptance of Mainstreamed Students with Mild Disabilities.

    Science.gov (United States)

    Culliver, Concetta; Obi, Sunday

    This study applied computer-assisted instruction (CAI) techniques to improve peer acceptance among 92 mainstreamed students with mild disabilities from 10 to 13 years of age. Participants in the treatment group received their generalized curriculum program (including mathematics, language arts, reading, health, social studies, and science)…

  14. Epstein-Barr virus-encoded latent membrane protein 1 modulates cyclin D1 by c-Jun/Jun B heterodimers

    Institute of Scientific and Technical Information of China (English)

    SONG; Xin; TAO; Yongguang; ZENG; Liang; YANG; Jing; TANG; F

    2005-01-01

    In our recent studies, we found that LMP1 encoded by Epstein-Barr virus could accelerate the formation of active c-Jun/Jun B heterodimer. We studied the regulation of cyclinD1 by c-Jun/Jun B heterodimers by laser scanning confocal influorescence microscopy, Western blot, luciferase activity assay, super-EMSA and flow cytometry in the Tet-on-LMP1 HNE2 cell line, in which LMP1 expression was regulated by Tet-on system. c-Jun/Jun B heterodimers induced by LMP1 could up regulate cyclin D1 promoter activity and expression. Overexpression of cyclinD1 accelerated the progression of cell cycle.

  15. High-Throughput Proteomic Approaches to the Elucidation of Potential Biomarkers of Chronic Allograft Injury (CAI

    Directory of Open Access Journals (Sweden)

    Hilary Cassidy

    2013-09-01

    Full Text Available This review focuses on the role of OMICs technologies, concentrating in particular on proteomics, in biomarker discovery in chronic allograft injury (CAI. CAI is the second most prevalent cause of allograft dysfunction and loss in the first decade post-transplantation, after death with functioning graft (DWFG. The term CAI, sometimes referred to as chronic allograft nephropathy (CAN, describes the deterioration of renal allograft function and structure as a result of immunological processes (chronic antibody-mediated rejection, and other non-immunological factors such as calcineurin inhibitor (CNI induced nephrotoxicity, hypertension and infection. Current methods for assessing allograft function are costly, insensitive and invasive; traditional kidney function measurements such as serum creatinine and glomerular filtration rate (GFR display poor predictive abilities, while the current “gold-standard” involving histological diagnosis with a renal biopsy presents its own inherent risks to the overall health of the allograft. As early as two years post-transplantation, protocol biopsies have shown more than 50% of allograft recipients have mild CAN; ten years post-transplantation more than 50% of the allograft recipients have progressed to severe CAN which is associated with diminishing graft function. Thus, there is a growing medical requirement for minimally invasive biomarkers capable of identifying the early stages of the disease which would allow for timely intervention. Proteomics involves the study of the expression, localization, function and interaction of the proteome. Proteomic technologies may be powerful tools used to identify novel biomarkers which would predict CAI in susceptible individuals. In this paper we will review the use of proteomics in the elucidation of novel predictive biomarkers of CAI in clinical, animal and in vitro studies.

  16. NWA10758: A New CV3 Chondrite Bearing a Giant CAI with Hibonite-Rich Wark-Lovering Rim

    Science.gov (United States)

    Ross, D. K.; Simon, J. I.; Zolensky, M.

    2017-01-01

    Northwest Africa (NWA) 10758 is a newly identified carbonaceous chondrite that is a Bali-like oxidized CV3. The large Ca-Al rich inclusion (CAI) in this sample is approx. 2.4 x 1.4 cm. The CAI is transitional in composition between type A and type B, with interior mineralogy dominated by melilite, plus less abundant spinel and Al-Ti rich diopside, and only very minor anorthite (Fig. 1A). This CAI is largely free of secondary alteration in the exposed section we examined, with almost no nepheline, sodalite or Ca-Fe silicates. The Wark-Lovering (WL) rim on this CAI is dominated by hibonite, with lower abundances of spinel and perovskite, and with hibonite locally overlain by melilite plus perovskite (as in Fig. 1B). Note that the example shown in 1B is exceptional. Around most of the CAI, hibonite + spinel + perovskite form the WL rim, without overlying melilite. The WL rim can be unusually thick, ranging from approx. 20 microns up to approx. 150 microns. A well-developed, stratified accretionary rim infills embayments of the CAI, and thins over protuberances in the convoluted CAI surface.

  17. Northwest Africa 10758: A New CV3 Chondrite Bearing a Giant CAI with Hibonite-Rich Wark-Lovering Rim

    Science.gov (United States)

    Ross, D. K.; Simon, J. I.; Zolensky, M.

    2017-01-01

    Northwest Africa (NWA) 10758 is a newly identified carbonaceous chondrite that is a Bali-like oxidized CV3. The large Ca-Al rich inclusion (CAI) in this sample is approx. 2.4 x 1.4 cm. The CAI is transitional in composition between type A and type B, with interior mineralogy dominated by melilite, plus less abundant spinel and Al-Ti rich diopside, and only very minor anorthite (Fig. 1A). This CAI is largely free of secondary alteration in the exposed section we examined, with almost no nepheline, sodalite or Ca-Fe silicates. The Wark-Lovering (WL) rim on this CAI is dominated by hibonite, with lower abundances of spinel and perovskite, and with hibonite locally overlain by melilite plus perovskite (as in Fig. 1B). Note that the example shown in 1B is exceptional. Around most of the CAI, hibonite + spinel + perovskite form the WL rim, without overlying melilite. The WL rim can be unusually thick, ranging from approx.20 microns up to approx. 150 microns. A well-developed, stratified accretionary rim infills embayments of the CAI, and thins over protuberances in the convoluted CAI surface.

  18. c-jun is differentially expressed in embryonic and adult neural precursor cells.

    Science.gov (United States)

    Kawashima, Fumiaki; Saito, Kengo; Kurata, Hirofumi; Maegaki, Yoshihiro; Mori, Tetsuji

    2017-01-16

    c-jun, a major component of AP-1 transcription factor, has a wide variety of functions. In the embryonic brain, c-jun mRNA is abundantly expressed in germinal layers around the ventricles. Although the subventricular zone (SVZ) of the adult brain is a derivative of embryonic germinal layers and contains neural precursor cells (NPCs), the c-jun expression pattern is not clear. To study the function of c-jun in adult neurogenesis, we analyzed c-jun expression in the adult SVZ by immunohistochemistry and compared it with that of the embryonic brain. We found that almost all proliferating embryonic NPCs expressed c-jun, but the number of c-jun immunopositive cells among proliferating adult NPCs was about half. In addition, c-jun was hardly expressed in post-mitotic migrating neurons in the embryonic brain, but the majority of c-jun immunopositive cells were tangentially migrating neuroblasts heading toward the olfactory bulb in the adult brain. In addition, status epilepticus is known to enhance the transient proliferation of adult NPCs, but the c-jun expression pattern was not significantly affected. These expression patterns suggest that c-jun has a pivotal role in the proliferation of embryonic NPCs, but it has also other roles in adult neurogenesis.

  19. Alternative communication network designs for an operational Plato 4 CAI system

    Science.gov (United States)

    Mobley, R. E., Jr.; Eastwood, L. F., Jr.

    1975-01-01

    The cost of alternative communications networks for the dissemination of PLATO IV computer-aided instruction (CAI) was studied. Four communication techniques are compared: leased telephone lines, satellite communication, UHF TV, and low-power microwave radio. For each network design, costs per student contact hour are computed. These costs are derived as functions of student population density, a parameter which can be calculated from census data for one potential market for CAI, the public primary and secondary schools. Calculating costs in this way allows one to determine which of the four communications alternatives can serve this market least expensively for any given area in the U.S. The analysis indicates that radio distribution techniques are cost optimum over a wide range of conditions.

  20. Purification and Activity of Antibacterial Substances Derived from Soil Streptomyces sp.CaiF1

    Institute of Scientific and Technical Information of China (English)

    Hui YANG; Guixiang PENG; Jianmin ZENG; Zhiyuan TAN

    2012-01-01

    [Objective] This study aimed to separate and purify antibacterial sub- stances from soil Streptomyces sp. CaiF1, and to explore the activities of this sub- stance. [Method] The antibacterial substances were separated and purified by Ethyl acetate extraction, macroporous adsorptive resin, silica gel chromatography and preparative high performance liquid chromatography (HPLC), and powdery mildew were taken as the indicating bacterial to study their activities. [Result] Antibacterial substances were purified and the stability analysis of the extracts from Streptomyces CaiF1 fermentation broth showed very stable at pH 2.0-pH 10.0, 100 ~C and changed very little under UV treatment for 24 h. Inhibition rate of powdery mildew was 69.7%. [Conclusion] The purified antibacterial substances showed good stability, which provided theoretical foundation for their structural identifications and future ap- plications.

  1. CAI Ding-fang——An Outstanding Neurologist of Integrative Medicine

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    @@ Prof. CAI Ding-fang, Ph.D., was born on Nov. 8, 1956 in Shanghai. In 1988, Prof. CAI received the Ph.D. degree from the Nanjing University of Traditional Chinese Medicine. He built an academic foundation of a strong Chinese medicine (CM) & integrative medicine research following Prof. SHEN Zi-yin, an academician of the Chinese Academy of Sciences, and accomplished a training course aiming specifically at the solid and broad basic theory, as well as the deep and systemic expertise. He then worked as a visiting scholar in the Medical Center of the University of Tokushima, Japan from July 1990 to July 1991, and as a post-Ph.D. in Toyama Medical and Pharmaceutical University from September 1994 to September 1995.

  2. STRAP regulates c-Jun ubiquitin-mediated proteolysis and cellular proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Reiner, Jennifer [Department of Cancer Biology, Vanderbilt University, School of Medicine, Nashville, TN (United States); Ye, Fei [Department of Biostatistics, Vanderbilt University, School of Medicine, Nashville, TN (United States); Kashikar, Nilesh D. [Department of Cancer Biology, Vanderbilt University, School of Medicine, Nashville, TN (United States); Datta, Pran K., E-mail: pran.datta@vanderbilt.edu [Department of Cancer Biology, Vanderbilt University, School of Medicine, Nashville, TN (United States); Department of Surgery, Vanderbilt University, School of Medicine, Nashville, TN (United States)

    2011-04-08

    Highlights: {yields} STRAP is specifically correlated with c-Jun expression and activation in fibroblasts. {yields} STRAP inhibits c-Jun ubiquitylation in vivo and prolongs the half-life of c-Jun. {yields} STRAP expression increases expression of the AP-1 target gene, cyclin D1, and promotes cell autonomous growth. -- Abstract: STRAP is a ubiquitous WD40 protein that has been implicated in tumorigenesis. Previous studies suggest that STRAP imparts oncogenic characteristics to cells by promoting ERK and pRb phosphorylation. While these findings suggest that STRAP can activate mitogenic signaling pathways, the effects of STRAP on other MAPK pathways have not been investigated. Herein, we report that STRAP regulates the expression of the c-Jun proto-oncogene in mouse embryonic fibroblasts. Loss of STRAP expression results in reduced phospho-c-Jun and total c-Jun but does not significantly reduce the level of two other early response genes, c-Myc and c-Fos. STRAP knockout also decreases expression of the AP-1 target gene, cyclin D1, which is accompanied by a reduction in cell growth. No significant differences in JNK activity or basal c-Jun mRNA levels were observed between wild type and STRAP null fibroblasts. However, proteasomal inhibition markedly increases c-Jun expression in STRAP knockout MEFs and STRAP over-expression decreases the ubiquitylation of c-Jun in 293T cells. Loss of STRAP accelerates c-Jun turnover in fibroblasts and ectopic over-expression of STRAP in STRAP null fibroblasts increases c-Jun expression. Collectively, our findings indicate that STRAP regulates c-Jun stability by decreasing the ubiquitylation and proteosomal degradation of c-Jun.

  3. Dilution effects on the controlled auto-ignition (CAI) combustion of hydrocarbon and alcohol fuels

    OpenAIRE

    Oakley, A.; Zhao, H.; Ma, T.; Ladommatos, N

    2001-01-01

    Copyright © 2001 SAE International. This paper is posted on this site with permission from SAE International. Further use of this paper is not permitted without permission from SAE This paper presents results from an experimental programme researching the in-cylinder conditions necessary to obtain homogenous CAI (or HCCI) combustion in a 4-stroke engine. The fuels under investigation include three blends of Unleaded Gasoline, a 95 RON Primary Reference Fuel, Methanol, and Ethanol. This wor...

  4. Experimental investigation of CAI combustion in a two-stroke poppet valve DI engine

    OpenAIRE

    Zhang, Yan

    2015-01-01

    This thesis was submitted for the award of Doctor of Philosophy and was awarded by Brunel University London Due to their ability to simultaneously reduce fuel consumption and NOx emissions, Controlled Auto Ignition (CAI) and HCCI combustion processes have been extensively researched over the last decade and adopted on prototype gasoline engines. These combustion processes were initially achieved on conventional two-stroke ported gasoline engines, but there have been significantly fewer stu...

  5. Numerical investigation of CAI Combustion in the Opposed- Piston Engine with Direct and Indirect Water Injection

    Science.gov (United States)

    Pyszczek, R.; Mazuro, P.; Teodorczyk, A.

    2016-09-01

    This paper is focused on the CAI combustion control in a turbocharged 2-stroke Opposed-Piston (OP) engine. The barrel type OP engine arrangement is of particular interest for the authors because of its robust design, high mechanical efficiency and relatively easy incorporation of a Variable Compression Ratio (VCR). The other advantage of such design is that combustion chamber is formed between two moving pistons - there is no additional cylinder head to be cooled which directly results in an increased thermal efficiency. Furthermore, engine operation in a Controlled Auto-Ignition (CAI) mode at high compression ratios (CR) raises a possibility of reaching even higher efficiencies and very low emissions. In order to control CAI combustion such measures as VCR and water injection were considered for indirect ignition timing control. Numerical simulations of the scavenging and combustion processes were performed with the 3D CFD multipurpose AVL Fire solver. Numerous cases were calculated with different engine compression ratios and different amounts of directly and indirectly injected water. The influence of the VCR and water injection on the ignition timing and engine performance was determined and their application in the real engine was discussed.

  6. Characterization of c-Jun from orange-spotted grouper, Epinephelus coioides involved in SGIV infection.

    Science.gov (United States)

    Wei, Shina; Huang, Youhua; Huang, Xiaohong; Qin, Qiwei

    2015-03-01

    The nuclear phosphoprotein c-Jun is a member of the AP1 family of transcription activating complex, can be induced by various extracellular stimuli such as virus infection. In this study, the c-Jun gene (Ec-c-Jun) was cloned from orange-spotted grouper, Epinephelus coioides. The full-length Ec-c-Jun cDNA is composed of 2046 bp and encodes a polypeptide of 328 amino acids with 81% identity of zebrafish. Amino acid alignment analysis indicated that Ec-c-Jun contained three conserved domains including a transactivation domain (TAD), a DNA-binding domain (DBD) and leucine zipper domain (LZD). RT-PCR results showed that Ec-c-Jun transcript was most abundant in spleen, kidney, heart and gill. The expression of Ec-c-Jun was up-regulated after challenged with Singapore grouper iridovirus (SGIV). To investigate the roles of Ec-c-Jun during SGIV infection, we constructed its dominant-negative mutant (DN-Ec-c-Jun) by deleting the major TAD that lacks amino acids 3-122. Fluorescence microscopy observation revealed that Ec-c-Jun and DN-Ec-c-Jun were expressed predominantly in the nucleus in transfected cells. Interestingly, the green fluorescence of Ec-c-Jun was congregated and co-localized with virus assembly sites at the late stage of SGIV infection. However, in DN-Ec-c-Jun transfected cells, no virus assembly sites were observed, and the distribution of fluorescence remained unchanged. Moreover, overexpression of DN-Ec-c-Jun in vitro delayed the occurrence of CPE induced by SGIV infection and inhibited the virus gene transcription. In addition, ectopic expression of DN-Ec-c-Jun was able to inhibit SGIV induced c-Jun/AP1 promoter activity in GS cells. Thus, we proposed that c-Jun transcription factor was essential for SGIV replication in vitro. Our results will contribute to understanding the crucial roles of JNK signaling pathway in fish virus infection.

  7. Nerve Injury-Induced c-Jun Activation in Schwann Cells Is JNK Independent

    Directory of Open Access Journals (Sweden)

    Charlotta Lindwall Blom

    2014-01-01

    Full Text Available We investigated (a if activation of the mitogen activated protein kinase (MAPK pathway was linked to the stress activated protein kinase (SAPK pathway and (b if JNK was required for activation of c-Jun in Schwann cells of rat sciatic nerve following injury. To this aim, ERK1/2 and the transcription factors c-Jun and ATF-3 were studied by immunohistochemistry in segments of transected nerves. We utilized pharmacological inhibitors of both signal transduction pathways in vitro to determine the effects on downstream signalling events, such as c-Jun activation, and on Schwann cell survival and proliferation. A transection induces c-Jun and ATF-3 transcription in Schwann cells. These events are followed by Schwann cell activation of c-Jun in the injured nerve. The MAPK inhibitor U0126 blocked ERK1/2 activation and reduced Schwann cell proliferation as well as induction of c-Jun transcription. The JNK inhibitor SP600125 reduced Schwann cell proliferation, but did not affect the expression of ERK1/2 or injury-induced increases in c-Jun or ATF-3 levels. Importantly, nerve injury induces Schwann cell activation of c-Jun by phosphorylation, which, in contrast to in sensory neurons, is JNK independent. MAP kinases, other than JNK, can potentially activate c-Jun in Schwann cells following injury; information that is crucial to create new nerve reconstruction strategies.

  8. OXYGEN ISOTOPIC COMPOSITIONS OF THE ALLENDE TYPE C CAIs: EVIDENCE FOR ISOTOPIC EXCHANGE DURING NEBULAR MELTING AND ASTEROIDAL THERMAL METAMORPHISM

    Energy Technology Data Exchange (ETDEWEB)

    Krot, A N; Chaussidon, M; Yurimoto, H; Sakamoto, N; Nagashima, K; Hutcheon, I D; MacPherson, G J

    2008-02-21

    Based on the mineralogy and petrography, coarse-grained, igneous, anorthite-rich (Type C) calcium-aluminum-rich inclusions (CAIs) in the CV3 carbonaceous chondrite Allende have been recently divided into three groups: (i) CAIs with melilite and Al,Ti-diopside of massive and lacy textures (coarse grains with numerous rounded inclusions of anorthite) in a fine-grained anorthite groundmass (6-1-72, 100, 160), (ii) CAI CG5 with massive melilite, Al,Ti-diopside and anorthite, and (iii) CAIs associated with chondrule material: either containing chondrule fragments in their peripheries (ABC, TS26) or surrounded by chondrule-like, igneous rims (93) (Krot et al., 2007a,b). Here, we report in situ oxygen isotopic measurements of primary (melilite, spinel, Al,Ti-diopside, anorthite) and secondary (grossular, monticellite, forsterite) minerals in these CAIs. Spinel ({Delta}{sup 17}O = -25{per_thousand} to -20{per_thousand}), massive and lacy Al,Ti-diopside ({Delta}{sup 17}O = -20{per_thousand} to -5{per_thousand}) and fine-grained anorthite ({Delta}{sup 17}O = -15{per_thousand} to -2{per_thousand}) in 100, 160 and 6-1-72 are {sup 16}O-enriched relative spinel and coarse-grained Al,Ti-diopside and anorthite in ABC, 93 and TS26 ({Delta}{sup 17}O ranges from -20{per_thousand} to -15{per_thousand}, from -15{per_thousand} to -5{per_thousand}, and from -5{per_thousand} to 0{per_thousand}, respectively). In 6-1-72, massive and lacy Al,Ti-diopside grains are {sup 16}O-depleted ({Delta}{sup 17}O {approx} -13{per_thousand}) relative to spinel ({Delta}{sup 17}O = -23{per_thousand}). Melilite is the most {sup 16}O-depleted mineral in all Allende Type C CAIs. In CAI 100, melilite and secondary grossular, monticellite and forsterite (minerals replacing melilite) are similarly {sup 16}O-depleted, whereas grossular in CAI 160 is {sup 16}O-enriched ({Delta}{sup 17}O = -10{per_thousand} to -6{per_thousand}) relative to melilite ({Delta}{sup 17}O = -5{per_thousand} to -3{per_thousand}). We infer

  9. CAI多媒體教學軟體之開發模式 Using an Instructional Design Model for Developing a Multimedia CAI Courseware

    Directory of Open Access Journals (Sweden)

    Hsin-Yih Shyu

    1995-09-01

    Full Text Available 無This article outlined a systematic instructional design model for developing a multimedia computer-aided instruction (CAI courseware. The model illustrated roles and tasks as two dimensions necessary in a CAI production teamwork. Four major components (Analysis, Design, Development, and Revise/Evaluation following by totally 25 steps are provided. Eight roles with each competent skills were identified. The model will be useful in serving as a framework for developing a mulrimedia CAI courseware for educators, instructional designers and CAI industry developers.

  10. Viral diversity of Junín virus field strains.

    Science.gov (United States)

    Goñi, Sandra E; Stephan, Betina I; Iserte, Javier A; Contigiani, Marta S; Lozano, Mario E; Tenorio, Antonio

    2011-09-01

    The Argentine Hemorrhagic Fever, an endemic disease present in a much of Argentina, is caused by the Junín virus (JUNV). Currently, there are sequences available from several strains of this virus, like those belonging to the vaccine lineage (XJ13, XJ#44 and Candid#1), as well as MC2 (rodent isolate) and IV4454 (human isolate). In this article, we report sequence information on two fragments of genomic segment S of viral isolates from the endemic area. A Nested-RT-PCR was used to amplify discrete genomic regions of 13 isolates of rodent and human origin. The bioinformatics studies revealed a great homogeneity of sequences among the JUNV isolates. The phylogenetic classification showed greater evolutionary distance between the old world arenaviruses (Lassa and LCM virus) than between the new world arenaviruses (JUNV and Machupo virus).

  11. Characterization of Meteorites by Focused Ion Beam Sectioning: Recent Applications to CAIs and Primitive Meteorite Matrices

    Science.gov (United States)

    Christoffersen, Roy; Keller, Lindsay P.; Han, Jangmi; Rahman, Zia; Berger, Eve L.

    2015-01-01

    Focused ion beam (FIB) sectioning has revolutionized preparation of meteorite samples for characterization by analytical transmission electron microscopy (TEM) and other techniques. Although FIB is not "non-destructive" in the purest sense, each extracted section amounts to no more than nanograms (approximately 500 cubic microns) removed intact from locations precisely controlled by SEM imaging and analysis. Physical alteration of surrounding material by ion damage, fracture or sputter contamination effects is localized to within a few micrometers around the lift-out point. This leaves adjacent material intact for coordinate geochemical analysis by SIMS, microdrill extraction/TIMS and other techniques. After lift out, FIB sections can be quantitatively analyzed by electron microprobe prior to final thinning, synchrotron x-ray techniques, and by the full range of state-of-the-art analytical field-emission scanning transmission electron microscope (FE-STEM) techniques once thinning is complete. Multiple meteorite studies supported by FIB/FE-STEM are currently underway at NASA-JSC, including coordinated analysis of refractory phase assemblages in CAIs and fine-grained matrices in carbonaceous chondrites. FIB sectioning of CAIs has uncovered epitaxial and other overgrowth relations between corundum-hibonite-spinel consistent with hibonite preceding corundum and/or spinel in non-equilibrium condensation sequences at combinations of higher gas pressures, dust-gas enrichments or significant nebular transport. For all of these cases, the ability of FIB to allow for coordination with spatially-associated isotopic data by SIMS provides immense value for constraining the formation scenarios of the particular CAI assemblage. For carbonaceous chondrites matrix material, FIB has allowed us to obtain intact continuous sections of the immediate outer surface of Murchison (CM2) after it has been experimentally ion processed to simulate solar wind space weathering. The surface

  12. Constraints on the Origin of Chondrules and CAIs from Short-Lived and Long-Lived Radionuclides

    Energy Technology Data Exchange (ETDEWEB)

    Kita, N T; Huss, G R; Tachibana, S; Amelin, Y; Nyquist, L E; Hutcheon, I D

    2005-10-24

    The high time resolution Pb-Pb ages and short-lived nuclide based relative ages for CAIs and chondrules are reviewed. The solar system started at 4567.2 {+-} 0.6Ma inferred from the high precision Pb-Pb ages of CAIs. Time scales of CAIs ({le}0.1Myr), chondrules (1-3Myr), and early asteroidal differentiation ({ge}3Myr) inferred from {sup 26}Al relative ages are comparable to the time scale estimated from astronomical observations of young star; proto star, classical T Tauri star and week-lined T Tauri star, respectively. Pb-Pb ages of chondrules also indicate chondrule formation occur within 1-3 Myr after CAIs. Mn-Cr isochron ages of chondrules are similar to or within 2 Myr after CAI formation. Chondrules from different classes of chondrites show the same range of {sup 26}Al ages in spite of their different oxygen isotopes, indicating that chondrule formed in the localized environment. The {sup 26}Al ages of chondrules in each chondrite class show a hint of correlation with their chemical compositions, which implies the process of elemental fractionation during chondrule formation events.

  13. New Evidence for 26Al in CAI and Chondrules from Type 3 Ordinary Chondrites

    Science.gov (United States)

    Srinivasan, G.; Russell, S. S.; MacPherson, G. J.; Huss, G. R.; Wasserburg, G. J.

    1996-03-01

    We have known since 1976 that 26A1 (tl/2 = 7.2 x 105 yrs) was alive in the early solar system, at a level of (26Al/27Al)o z 5 x 10-5 in calcium-aluminum inclusions (CAI). However, several outstanding questions remain. Little evidence for 26A1 has been found in other chondritic material, and none has been found in differentiated meteorites. These results might imply that 26A1 was heterogeneously distributed in the nebula or by mineralogic site in nebular dust, or they might reflect differences in time of formation. There are strict limitations on finding evidence of 26A1 in normal chondrules with bulk Al/Mg ~ 0.1, since even quenched, perfectly preserved, late-stage glasses would have low Al/Mg. Primary plagioclase crystals provide the only possibility, but these only crystallize rarely in melts within the compositional range of normal chondrules. Also, metamorphism can erase the evidence in high-AI/Mg phases. To address these issues, we have conducted a search for chondrules and CAI with high-Al/Mg phases suitable for ion-probe measurement in type 3 ordinary chondrites. Previous work has revealed evidence for 26Al in a plagioclase bearing, olivine-pyroxene class from Semarkona (LL3.0; (26Al/27Al)o = 7.7+/-2.1 x 10-6)), a plagioclase-rich object from Bovedy (L3.7?; 2.5+/-1.2 x 10-7), in separated plagioclase from St. Marguerite (H4; 2.0+/-0.6 x 10-7), an isolated hibonite grain from Dhajala (H3.8; 8.4+0.5 x 10-6), and in Al2O3 and hibonite grains ((26Al/27Al)o = 2-5 x 10-5; [GRH, unpublished]) from acid residues of Semarkona, Bishunpur (LL3.1), and Krymka (LL3.1). We have identified and measured Al-Mg isotope systematics in two CAI and seven chondrules from ordinary chondrites of low metamorphic grade and have found clear evidence for 26A1 in both CAI and in two chondrules.

  14. The Clinical Experiences of Dr.CAI Gan in Treating Chronic Constipation

    Institute of Scientific and Technical Information of China (English)

    ZHANG Zheng-li; ZHU Mei-ping; LIU Qun; LEI Yun-xia

    2009-01-01

    @@ Prof.CAI Gan (蔡淦) is an academic leader in TCM treatment of the spleen and stomach disease.He insisted that liver depression, spleen deficiency and poor nourishment of the intestines are the core of pathogenesis for chronic constipation.Therefore he often treats the disease by strengthening the spleen,relieving the depressed liver, nourishing yin and moistening the intestines.Meanwhile he attaches great importance to syndrome differentiation and comprehensive regulation and treatment.As a result,good therapeutic effects are often achieved.The authors summarized his ways for treating chronic constipation with the following 10 methods, which are introduced below.

  15. Expression of JunB Induced by X-rays in Mice

    Institute of Scientific and Technical Information of China (English)

    HONG WAN; HIROSHI ISHIHARA

    2004-01-01

    To explore JunB gene expression in spleen cells of mice after the whole body irradiation as well as in normal hematopoietic and leukemia cells in the primary culture after different dosages of X-ray irradiation. Methods Spleen cells were isolated from the mice irradiated with 3 Gy X-rays. Primary cultured cells from mice were incubated in different intervals after X-irradiation at different dosages. Total RNA was extracted from the cells and the fluctuation of JunB mRNA level was assessed by the RNA ratio of JunB/β-actin measured by quantitative Northern blot hybridization. Results After the mice were exposed to 3 Gy X-rays irradiation, JunB expression in spleen cells was remarkably and rapidly increased, and reached its peak 0.5 h later in C3H/He mice and 1 h later in Balb/c mice. In the primary culture of normal spleen and leukemia cells, JunB mRNA levels increased 30 min after irradiation. The enhanced levels of JunB mRNA were returned to a normal level within 240 min after irradiation. Conclusions JunB gene is responsive to ionizing irradiation and is induced at immediate-early phase after the stimulation. This suggests that the JunB gene plays an important role in the early process of the cells against radiation.

  16. Cholesterol affects gene expression of the Jun family in colon carcinoma cells using different signaling pathways.

    Science.gov (United States)

    Scheinman, Eyal J; Rostoker, Ran; Leroith, Derek

    2013-07-15

    Hyperlipidemia and hypercholesterolemia have been found to be important factors in cancer development and metastasis. However, the metabolic mechanism and downstream cellular processes following cholesterol stimulation are still unknown. Here we tested the effect of cholesterol on MC-38 colon cancer cells. Using Illumina gene array technology we found a number of genes that were differentially expressed following short term (20-40 min) and longer term (between 2 and 5h) cholesterol stimulation. Three genes were consistently increased at these time points; c-Jun, Jun-B and the chemokine CXCL-1. We have previously shown that cholesterol stimulation leads to PI3K/Akt phosphorylation, and now demonstrated that cholesterol inhibits ERK1/2 phosphorylation; both effects reversed when cholesterol is depleted from lipid rafts using methyl-β-cyclodextrin (MBCD). In addition, vanadate, an inhibitor of phosphatases, reversed the cholesterol inhibition of ERK1/2 phosphorylation. Specific inhibition of p-Akt by wortmannin did not affect cholesterol's stimulation of the expression of c-Jun and Jun-B, however the vanadate effect of increasing p-ERK1/2, inhibited c-Jun expression, specifically, and the MBCD effect of increasing p-ERK and inhibiting p-Akt reduced c-Jun expression. In contrast MBCD and vanadate both enhanced Jun-B gene expression in the presence of cholesterol and elevation of ERK phosphorylation. Thus there is apparently, a differential signaling pathway whereby cholesterol enhances gene expression of the Jun family members.

  17. c-Jun activation is associated with proliferation and angiogenesis in invasive breast cancer

    NARCIS (Netherlands)

    Vleugel, M.M.; Greijer, A.E.; Bos, R.; Wall, E. van der; Diest, P.J. van

    2006-01-01

    c-Jun is a component of the transcription factor activator protein 1 (AP-1), which binds and activates transcription at TRE/AP-1 elements. Extra- or intracellular signals, including growth factors, transforming oncoproteins, and UV irradiation, stimulate phosphorylation of c-Jun at serine 63/73 and

  18. Intelligent CAI.

    Science.gov (United States)

    1975-10-01

    of industria !, technological, and sociological interest- invaluable information for executives and professionals who must keep up to date. The...BEVERAGE 1A HOT CHOCOLATE MB TEA IBI WITH LEMON HB2 WITH SUGAR AND CREAM 1C COFFEE 11 SUBSTITUTE WOR’ JN &TATCIKMT Before we end this

  19. Ca-Fe and Alkali-Halide Alteration of an Allende Type B CAI: Aqueous Alteration in Nebular or Asteroidal Settings

    Science.gov (United States)

    Ross, D. K.; Simon, J. I.; Simon, S. B.; Grossman, L.

    2012-01-01

    Ca-Fe and alkali-halide alteration of CAIs is often attributed to aqueous alteration by fluids circulating on asteroidal parent bodies after the various chondritic components have been assembled, although debate continues about the roles of asteroidal vs. nebular modification processes [1-7]. Here we report de-tailed observations of alteration products in a large Type B2 CAI, TS4 from Allende, one of the oxidized subgroup of CV3s, and propose a speculative model for aqueous alteration of CAIs in a nebular setting. Ca-Fe alteration in this CAI consists predominantly of end-member hedenbergite, end-member andradite, and compositionally variable, magnesian high-Ca pyroxene. These phases are strongly concentrated in an unusual "nodule" enclosed within the interior of the CAI (Fig. 1). The Ca, Fe-rich nodule superficially resembles a clast that pre-dated and was engulfed by the CAI, but closer inspection shows that relic spinel grains are enclosed in the nodule, and corroded CAI primary phases interfinger with the Fe-rich phases at the nodule s margins. This CAI also contains abundant sodalite and nepheline (alkali-halide) alteration that occurs around the rims of the CAI, but also penetrates more deeply into the CAI. The two types of alteration (Ca-Fe and alkali-halide) are adjacent, and very fine-grained Fe-rich phases are associated with sodalite-rich regions. Both types of alteration appear to be replacive; if that is true, it would require substantial introduction of Fe, and transport of elements (Ti, Al and Mg) out of the nodule, and introduction of Na and Cl into alkali-halide rich zones. Parts of the CAI have been extensively metasomatized.

  20. Caiçaras, caboclos and natural resources: rules and scale patterns Caiçaras, caboclos e recursos naturais: regras e padrões de escala

    Directory of Open Access Journals (Sweden)

    Alpina Begossi

    1999-12-01

    Full Text Available One important question concerning the sustainability of local or native populations refers to their interaction with local and global institutions. We should expect that populations with capacity to interact economically and politically with institutions, might show a better chance for their ecological and cultural continuity, as well as for their system of trade and subsistence. The level of ecological and social interaction of local populations, following concepts from ecology, occurs on different scales: for example, from the territories of individual fishermen on the Atlantic Forest coast to organizations of community Extractive Reserves in the Amazon. The scale of organization (individual/family/community may influence the capacity to deal with institutions. This study analyses how Brazilian native populations, especially caiçaras of the Atlantic Forest coast, and caboclos from the Amazon, have interacted with regional, national and global institutions, concerning environmental demands. Concepts such as common management, natural capital, resilience and sustainability are useful to understand these illustrative cases.Uma questão importante da sustentabilidade de populações locais ou nativas se refere à interação com as instituições locais e globais. Podemos esperar que populações que demonstrem capacidade de interagir de forma econômica e política com as instituições apresentem também uma chance maior de continuidade cultural e ecológica, assim como de seus sistemas de troca e subsistência. O nível da interação ecológica e social das populações locais, seguindo conceitos da ecologia, ocorrem sob escalas diferentes: por exemplo, dos territórios individuais de pescadores da Mata Atlântica às organizações de comunidades em Reservas Extrativistas, na Amazônia. A escala organizacional (individual/familiar/comunitária pode influenciar a capacidade de lidar com as instituições.Esse estudo analisa como popula

  1. Automated COBOL code generation for SNAP-I CAI development and maintenance procedures

    Energy Technology Data Exchange (ETDEWEB)

    Buhrmaster, M.A.; Duncan, L.D.; Hume, R.; Huntley, A.F.

    1988-07-01

    In designing and implementing a computer aided instruction (CAI) prototype for the Navy Management System Support Office (NAVMASSO) as part of the Shipboard Nontactical ADP Program (SNAP), Data Systems Engineering Organization (DSEO) personnel developed techniques for automating the production of COBOL source code for CAI applications. This report discusses the techniques applied, which incorporate the use of a database management system (DBMS) to store, access, and manipulate the data necessary for producing COBOL source code automatically. The objective for developing the code generation techniques is to allow for the production of future applications in an efficient and reliable manner. This report covers the standards and conventions defined, database tables created, and the host language interface program used for generating COBOL source files. The approach is responsible for producing 85 percent of an 830,000 line COBOL application, in approximately one year's time. This code generation program generated transaction processing routines to be executed under the DM6TP NAVMASSO distributed processing environment on the Honeywell DPS-6 minicomputers, representing the standard SNAP-I environment.

  2. Estado nutricional y adecuación del menú en los CAI de Villa Gesell

    OpenAIRE

    2014-01-01

    Los Centros de Atención Integral (C.A.I) son unidades pertenecientes al PROMIN en los que se combinan prestaciones pedagógicas y de estimulación con complementación alimentaria en áreas de alta concentración de pobreza estructural. Objetivos: Evaluar el estado nutricional de los niños que asisten a los C.A.I. de Villa Gesell y la adecuación del menú brindado en estos a las necesidades nutricionales. Material y Método: Se procedió a tomar mediciones antropométricas tales como...

  3. A Comparative Study to Evaluate the Effectiveness of Computer Assisted Instruction (CAI) versus Class Room Lecture (RL) for Computer Science at ICS Level

    Science.gov (United States)

    Kausar, Tayyaba; Choudhry, Bushra Naoreen; Gujjar, Aijaz Ahmed

    2008-01-01

    This study was aimed to evaluate the effectiveness of CAI vs. classroom lecture for computer science at ICS level. The objectives were to compare the learning effects of two groups with class room lecture and computer assisted instruction studying the same curriculum and the effects of CAI and CRL in terms of cognitive development. Hypothesis of…

  4. Rice From Mercury Contaminated Areas in Guizhou Province Induces c-jun Expression in Rat Brain

    Institute of Scientific and Technical Information of China (English)

    JIN-PING CHENG; WEN-HUA WANG; LI-YA QU; JIN-PING JIA; MIN ZHENG; XIU-LING JI; TAO YUAN

    2005-01-01

    Objective Mercury (Hg), as one of the priority pollutants and also a hot topic of frontier environmental research in many countries, has been paid higher attention in the world since the middle of the last century. Guizhou Province (at N24°30′-29°13′, E103°1′-109°30′, 1 100 m above the sea level, with subtropical humid climate) in southwest China is an important mercury production center. It has been found that the mercury content in most media of aquatics, soil, atmosphere and in biomass of corns, plants and animals, is higher than the national standard.The present study aims to explore the influence of mercury pollution on the health of local citizens. Methods The effect of rice from two mercury polluted experimental plots of Guizhou Province on the expression of c-jun mRNA in rat brain and c-jun protein in cortex, hippocampus and ependyma was observed using reverse transcription polymerase chain reaction (RT-PCR) and immunocytochemical methods. Results The results showed that the mercury polluted rice induced expression of c-jun mRNA and its protein significantly. Selenium can reduce Hg uptake, an antagonism between selenium and mercury on the expression of c-jun mRNA and c-jun protein. Conclusion c-jun participates in the toxicity process of brain injury by mercury polluted rice, the expression of c- jun mRNA in brain, and c-jun protein in rat cortex and hippocampus can predict neurotoxicity of mercury polluted rice. People should be advised to be cautious in eating any kind of Hg-polluted foods. To reveal the relationship between c-jun induction and apoptosis, further examinations are required.

  5. Linking CAI abundance to polarimetric response in a population of ancient asteroids

    Science.gov (United States)

    Devogele, Maxime; Tanga, Paolo; Bendjoya, Philippe; Rivet, Jean-Pierre; Surdej, Jean; Bus, Schelte J.; Sunshine, Jessica M.; Cellino, Alberto; Campins, Humberto; Licandro, Javier; Pinilla-Alonso, Noemi; Carry, Benoit

    2016-10-01

    Polarimetry constitutes one of the fundamental tools for characterizing the surface texture and composition of airless Solar System bodies. In 2006, polarimetric observations led to the discovery of a new type of asteroids, which displays a peculiar polarimetric response. These asteroids are collectively known as "Barbarians", from (234) Barbara the first discovered one.The most commonly accepted explanation for this perculiar polarization response seems to be the presence of a high percentage of fluffy-type Calcium Aluminium-rich Inclusions (CAIs), whose optical properties could produce the observed polarization. Their reflectance spectra also exibit an absorption feature in the near-infrared around 2.1-2.2 microns, that is characteristic of this peculiar group.Based on these results, we organized a systematic polarimetric and near-infrared observational campaign of known Barbarians or candidate asteroids. These campaigns include members of the family of 1040 Klumpkea, 2085 Henan and 729 Watsonia, which are known to contain Barbarian and/or L-type asteroids also suspected to have such a polarimetric behaviour. We have made use of the ToPo polarimeter at the 1m telescope of the Centre pédagogique Planète et Univers (C2PU, Observatoire de la Côte d'Azur, France). The spectroscopic observations in the near-infrared were obtained with the SpeX instrument at the NASA's InfraRed Telescope Facility (IRTF).By combining polarimetry and spectroscopy we find a correlation between the abundance of CAIs and the inversion angle of the phase-polarization curve of Barbarian asteroids. This is the first time that a direct link has been established between a specific polarimetric response and the surface composition of asteroids. In addition, we find a considerable variety of CAI abundance from one object to the other, consistent with a wide range of possible albedos. Since these asteroids constitute a reservoir of primitive Solar System material, understanding their origin can

  6. From Corporate Social Responsibility, through Entrepreneurial Orientation, to Knowledge Sharing: A Study in Cai Luong (Renovated Theatre) Theatre Companies

    Science.gov (United States)

    Tuan, Luu Trong

    2015-01-01

    Purpose: This paper aims to examine the role of antecedents such as corporate social responsibility (CSR) and entrepreneurial orientation in the chain effect to knowledge sharing among members of Cai Luong theatre companies in the Vietnamese context. Knowledge sharing contributes to the depth of the knowledge pool of both the individuals and the…

  7. Hunting and use of terrestrial fauna used by Caiçaras from the Atlantic Forest coast (Brazil

    Directory of Open Access Journals (Sweden)

    Alves Rômulo RN

    2009-11-01

    Full Text Available Abstract Background The Brazilian Atlantic Forest is considered one of the hotspots for conservation, comprising remnants of rain forest along the eastern Brazilian coast. Its native inhabitants in the Southeastern coast include the Caiçaras (descendants from Amerindians and European colonizers, with a deep knowledge on the natural resources used for their livelihood. Methods We studied the use of the terrestrial fauna in three Caiçara communities, through open-ended interviews with 116 native residents. Data were checked through systematic observations and collection of zoological material. Results The dependence on the terrestrial fauna by Caiçaras is especially for food and medicine. The main species used are Didelphis spp., Dasyprocta azarae, Dasypus novemcinctus, and small birds (several species of Turdidae. Contrasting with a high dependency on terrestrial fauna resources by native Amazonians, the Caiçaras do not show a constant dependency on these resources. Nevertheless, the occasional hunting of native animals represents a complimentary source of animal protein. Conclusion Indigenous or local knowledge on native resources is important in order to promote local development in a sustainable way, and can help to conserve biodiversity, particularly if the resource is sporadically used and not commercially exploited.

  8. Phenotypic diversity and correlation between white-opaque switching and the CAI microsatellite locus in Candida albicans.

    Science.gov (United States)

    Hu, Jian; Guan, Guobo; Dai, Yu; Tao, Li; Zhang, Jianzhong; Li, Houmin; Huang, Guanghua

    2016-08-01

    Candida albicans is a commensal fungal pathogen that is often found as part of the human microbial flora. The aim of the present study was to establish a relationship between diverse genotypes and phenotypes of clinical isolates of C. albicans. Totally 231 clinical isolates were collected and used for genotyping and phenotypic switching analysis. Based on the microsatellite locus (CAI) genotyping assay, 65 different genotypes were identified, and some dominant types were found in certain human niches. For example, the genotypes of 30-44 and 30-45 were enriched in vaginal infection samples. C. albicans has a number of morphological forms including the single-celled yeasts, multicellular filaments, white, and opaque cell types. The relationship between the CAI genotype and the ability to undergo phenotypic switching was examined in the clinical isolates. We found that the strains with longer CAA/G repeats in both alleles of the CAI locus were more opaque competent. We also discovered that some MTL heterozygous (a/alpha) isolates could undergo white-opaque switching when grown on regular culture medium (containing glucose as the sole carbon source). Our study establishes a link between phenotypic switching and genotypes of the CAI microsatellite locus in clinical isolates of C. albicans.

  9. Changes in flavour and microbial diversity during natural fermentation of suan-cai, a traditional food made in Northeast China.

    Science.gov (United States)

    Wu, Rina; Yu, Meiling; Liu, Xiaoyu; Meng, Lingshuai; Wang, Qianqian; Xue, Yating; Wu, Junrui; Yue, Xiqing

    2015-10-15

    We measured changes in the main physical and chemical properties, flavour compounds and microbial diversity in suan-cai during natural fermentation. The results showed that the pH and concentration of soluble protein initially decreased but were then maintained at a stable level; the concentration of nitrite increased in the initial fermentation stage and after reaching a peak it decreased significantly to a low level by the end of fermentation. Suan-cai was rich in 17 free amino acids. All of the free amino acids increased in concentration to different degrees, except histidine. Total free amino acids reached their highest levels in the mid-fermentation stage. The 17 volatile flavour components identified at the start of fermentation increased to 57 by the mid-fermentation stage; esters and aldehydes were in the greatest diversity and abundance, contributing most to the aroma of suan-cai. Bacteria were more abundant and diverse than fungi in suan-cai; 14 bacterial species were identified from the genera Leuconostoc, Bacillus, Pseudomonas and Lactobacillus. The predominant fungal species identified were Debaryomyces hansenii, Candida tropicalis and Penicillium expansum.

  10. Teaching Critical Thinking Skills with CAI: A Design by Two Researchers Shows Computers Can Make a Difference.

    Science.gov (United States)

    Bass, George M., Jr.; Perkins, Harvey W.

    1984-01-01

    Describes a project which involved designing a nine-week course utilizing computer assisted instruction (CAI) to teach seventh graders critical thinking skills. Results indicate measurable gains were made in the critical thinking skills of verbal analogy and inductive/deductive reasoning, although no consistent gains were made in logical reasoning…

  11. From Corporate Social Responsibility, through Entrepreneurial Orientation, to Knowledge Sharing: A Study in Cai Luong (Renovated Theatre) Theatre Companies

    Science.gov (United States)

    Tuan, Luu Trong

    2015-01-01

    Purpose: This paper aims to examine the role of antecedents such as corporate social responsibility (CSR) and entrepreneurial orientation in the chain effect to knowledge sharing among members of Cai Luong theatre companies in the Vietnamese context. Knowledge sharing contributes to the depth of the knowledge pool of both the individuals and the…

  12. Two years since SSAMS: Status of {sup 14}C AMS at CAIS

    Energy Technology Data Exchange (ETDEWEB)

    Ravi Prasad, G.V.; Cherkinsky, Alexander; Culp, Randy A.; Dvoracek, Doug K.

    2015-10-15

    The NEC 250 kV single stage AMS accelerator (SSAMS) was installed two years ago at the Center for Applied Isotope Studies (CAIS), University of Georgia. The accelerator is primarily being used for radiocarbon measurements to test the authenticity of natural and bio-based samples while all other samples such as geological, atmospheric, marine and archaeological. are run on the 500 kV, NEC 1.5SDH-1 model tandem accelerator, which has been operating since 2001. The data obtained over a six months period for OXI, OXII, ANU sucrose and FIRI-D are discussed. The mean value of ANU sucrose observed to be slightly lower than the consensus value. The processed blanks on SSAMS produce lower apparent age compared to the tandem accelerator as expected.

  13. 物理教学中CAI的应用%CAI in Physics Teaching

    Institute of Scientific and Technical Information of China (English)

    梁继军; 王建东

    2004-01-01

    随着计算机技术的迅猛发展及计算机的大量普及,许多中学配备了多媒体教室,建立了电教中心,为计算机辅助教学(CAI)打下了硬件基础。如何认识CAI在教学中的地位,充分发挥CAI在教学中的作用,是摆在广大教育工作者面前的一个重要课题。笔者拟就CAI对物理教学中的影响、在物理教学中的应用以及目前存在的问题谈几点拙见。

  14. Dietary Changes over Time in a Caiçara Community from the Brazilian Atlantic Forest

    Directory of Open Access Journals (Sweden)

    Priscila L. MacCord

    2006-12-01

    Full Text Available Because they are occurring at an accelerated pace, changes in the livelihoods of local coastal communities, including nutritional aspects, have been a subject of interest in human ecology. The aim of this study is to explore the dietary changes, particularly in the consumption of animal protein, that have taken place in Puruba Beach, a rural community of caiçaras on the São Paulo Coast, Brazil, over the 10-yr period from 1992-1993 to 2002-2003. Data were collected during six months in 1992-1993 and during the same months in 2002-2003 using the 24-hr recall method. We found an increasing dependence on external products in the most recent period, along with a reduction in fish consumption and in the number of fish species eaten. These changes, possibly associated with other nonmeasured factors such as overfishing and unplanned tourism, may cause food delocalization and a reduction in the use of natural resources. Although the consequences for conservation efforts in the Atlantic Forest and the survival of the caiçaras must still be evaluated, these local inhabitants may be finding a way to reconcile both the old and the new dietary patterns by keeping their houses in the community while looking for sources of income other than natural resources. The prospect shown here may reveal facets that can influence the maintenance of this and other communities undergoing similar processes by, for example, shedding some light on the ecological and economical processes that may occur within their environment and in turn affect the conservation of the resources upon which the local inhabitants depend.

  15. JunB mediates basal- and TGFβ1-induced smooth muscle cell contractility.

    Directory of Open Access Journals (Sweden)

    Aruna Ramachandran

    Full Text Available Smooth muscle contraction is a dynamic process driven by acto-myosin interactions that are controlled by multiple regulatory proteins. Our studies have shown that members of the AP-1 transcription factor family control discrete behaviors of smooth muscle cells (SMC such as growth, migration and fibrosis. However, the role of AP-1 in regulation of smooth muscle contractility is incompletely understood. In this study we show that the AP-1 family member JunB regulates contractility in visceral SMC by altering actin polymerization and myosin light chain phosphorylation. JunB levels are robustly upregulated downstream of transforming growth factor beta-1 (TGFβ1, a known inducer of SMC contractility. RNAi-mediated silencing of JunB in primary human bladder SMC (pBSMC inhibited cell contractility under both basal and TGFβ1-stimulated conditions, as determined using gel contraction and traction force microscopy assays. JunB knockdown did not alter expression of the contractile proteins α-SMA, calponin or SM22α. However, JunB silencing decreased levels of Rho kinase (ROCK and myosin light chain (MLC20. Moreover, JunB silencing attenuated phosphorylation of the MLC20 regulatory phosphatase subunit MYPT1 and the actin severing protein cofilin. Consistent with these changes, cells in which JunB was knocked down showed a reduction in the F:G actin ratio in response to TGFβ1. Together these findings demonstrate a novel function for JunB in regulating visceral smooth muscle cell contractility through effects on both myosin and the actin cytoskeleton.

  16. Persistent induction of c-fos and c-jun expression by asbestos

    Energy Technology Data Exchange (ETDEWEB)

    Heintz, N.H.; Mossman, B.T. (Univ. of Vermont College of Medicine, Burlington (United States)); Janssen, Y.M. (Univ. of Vermont College of Medicine, Burlington (United States) Univ. of Limburg, Maastricht (Netherlands))

    1993-04-15

    To investigate the mechanisms of asbestos-induced carcinogenesis, expression of c-fos and c-jun protooncogenes was examined in rat pleural mesothelial cells and hamster tracheal epithelial cells after exposure to crocidolite or chrysotile asbestos. In contrast to phorbol 12-myristate 13-acetate, which induces rapid and transient increases in c-fos and c-jun mRNA, asbestos causes 2- to 5-fold increases in c-fos and c-jun mRNA that persist for at least 24 hr in mesothelial cells. The induction of c-fos and c-jun mRNA by asbestos in mesothelial cells is dose-dependent and is most pronounced with crocidolite, the type of asbestos most pathogenic in the causation of pleural mesothelioma. Induction of c-jun gene expression by asbestos occurs in tracheal epithelial cells but is not accompanied by a corresponding induction of c-fos gene expression. In both cell types, asbestos induces increases in protein factors that bind specifically to the DNA sites that mediate gene expression by the AP-1 family of transcription factors. The persistent induction of AP-1 transcription factors by asbestos suggests a model of asbestos-induced carcinogenesis involving chronic stimulation of cell proliferation through activation of the early response gene pathway that includes c-jun and/or c-fos. 30 refs., 5 figs.

  17. JAC, a direct target of oncogenic transcription factor Jun, is involved in cell transformation and tumorigenesis.

    Science.gov (United States)

    Hartl, M; Reiter, F; Bader, A G; Castellazzi, M; Bister, K

    2001-11-20

    Using subtractive hybridization techniques, we have isolated a gene termed JAC that is strongly and specifically activated in avian fibroblasts transformed by the v-jun oncogene of avian sarcoma virus 17 (ASV17), but not in cells transformed by other oncogenic agents. Furthermore, JAC is highly expressed in cell lines derived from jun-induced avian fibrosarcomas. Kinetic analysis using a doxycycline-controlled conditional cell transformation system showed that expression of the 0.8-kb JAC mRNA is induced rapidly upon activation of the oncogenic v-jun allele. Nucleotide sequence analysis and transcriptional mapping revealed that the JAC gene contains two exons, with the longest ORF confined to exon 2. The deduced 68-amino acid chicken JAC protein is rich in cysteine residues and displays 37% sequence identity to mammalian high-sulfur keratin-associated proteins. The promoter region of JAC contains a consensus (5'-TGACTCA-3') and a nonconsensus (5'-TGAGTAA-3') AP-1 binding site in tandem, which are both specifically bound by the Gag-Jun hybrid protein encoded by ASV17. Mutational analysis revealed that the two AP-1 sites confer strong transcriptional activation by Gag-Jun in a synergistic manner. Ectopic expression of JAC in avian fibroblasts leads to anchorage-independent growth, strongly suggesting that deregulation of JAC is an essential event in jun-induced cell transformation and tumorigenesis.

  18. c-jun gene expression in human cells exposed to either ionizing radiation or hydrogen peroxide

    Energy Technology Data Exchange (ETDEWEB)

    Collart, F.R.; Horio, M.; Huberman, E.

    1993-06-01

    We investigated the role of reactive oxygen intermediates (ROIs) and protein kinase C (PKC) in radiation- and H{sub 2}O{sub 2}-evoked c-jun gene expression in human HL-205 cells. This induction of c-jun gene expression could be prevented by pretreatment of the cells with Nacetylcysteine (an antioxidant) or H7 (a PKC and PKA inhibitor) but not by HA1004, a PKA inhibitor, suggesting a role for ROls and PKC in mediating c-jun gene expression. We also investigated potential differences in c-jun gene expression in a panel of normal and tumor cells untreated or treated with ionizing radiation or H{sub 2}O{sub 2}. Treatment with radiation or H{sub 2}O{sub 2} produced a varied response, from some reduction to an increase of more than an order of magnitude in the steady-state level of c-jun mRNA. These data indicate that although induction of c-jun may be a common response to ionizing radiation and H{sub 2}O{sub 2}, this response was reduced or absent in some cell types.

  19. VARIABLE AND EXTREME IRRADIATION CONDITIONS IN THE EARLY SOLAR SYSTEM INFERRED FROM THE INITIAL ABUNDANCE OF {sup 10}Be IN ISHEYEVO CAIs

    Energy Technology Data Exchange (ETDEWEB)

    Gounelle, Matthieu [Laboratoire de Mineralogie et de Cosmochimie du Museum, CNRS and Museum National d' Histoire Naturelle, UMR 7202, CP52, 57 rue Cuvier, F-75005 Paris (France); Chaussidon, Marc; Rollion-Bard, Claire, E-mail: gounelle@mnhn.fr [Centre de Recherches Petrographiques et Geochimiques, CRPG-CNRS, BP 20, F-54501 Vandoeuvre-les-Nancy Cedex (France)

    2013-02-01

    A search for short-lived {sup 10}Be in 21 calcium-aluminum-rich inclusions (CAIs) from Isheyevo, a rare CB/CH chondrite, showed that only 5 CAIs had {sup 10}B/{sup 11}B ratios higher than chondritic correlating with the elemental ratio {sup 9}Be/{sup 11}B, suggestive of in situ decay of this key short-lived radionuclide. The initial ({sup 10}Be/{sup 9}Be){sub 0} ratios vary between {approx}10{sup -3} and {approx}10{sup -2} for CAI 411. The initial ratio of CAI 411 is one order of magnitude higher than the highest ratio found in CV3 CAIs, suggesting that the more likely origin of CAI 411 {sup 10}Be is early solar system irradiation. The low ({sup 26}Al/{sup 27}Al){sub 0} [{<=} 8.9 Multiplication-Sign 10{sup -7}] with which CAI 411 formed indicates that it was exposed to gradual flares with a proton fluence of a few 10{sup 19} protons cm{sup -2}, during the earliest phases of the solar system, possibly the infrared class 0. The irradiation conditions for other CAIs are less well constrained, with calculated fluences ranging between a few 10{sup 19} and 10{sup 20} protons cm{sup -2}. The variable and extreme value of the initial {sup 10}Be/{sup 9}Be ratios in carbonaceous chondrite CAIs is the reflection of the variable and extreme magnetic activity in young stars observed in the X-ray domain.

  20. Parathyroid hormone induces c-fos and c-jun messenger RNA in rat osteoblastic cells

    Science.gov (United States)

    Clohisy, J. C.; Scott, D. K.; Brakenhoff, K. D.; Quinn, C. O.; Partridge, N. C.

    1992-01-01

    PTH is a potent regulator of osteoblast gene expression, yet the nuclear events that mediate PTH action are poorly understood. We were interested in identifying immediate early genes which may regulate PTH-altered gene expression in the osteoblast. Therefore, we examined the effects of PTH on c-fos and c-jun gene expression in a rat osteoblastic cell line (UMR 106-01). Under control conditions, c-fos and c-jun mRNAs were present at low basal levels. After PTH treatment, c-fos mRNA abundance dramatically increased, with a maximal and transient response at 30 min. PTH also stimulated an increase in c-jun mRNA, but in a biphasic manner, with maximal levels at 30 min and 2 h. These responses were dose dependent, not altered by cotreatment with the protein synthesis inhibitor cycloheximide, and preceded PTH-induced expression of matrix metallo-proteinase-1 mRNA. Nuclear run-on assays demonstrated an increased rate of c-fos and c-jun transcription after PTH exposure. To determine the signal transduction pathways involved, second messenger analogs were tested for their ability to mimic the effects of PTH. 8-Bromo-cAMP and phorbol 12-myristate 13-acetate (PMA) caused increases in the abundance of c-fos and c-jun transcripts. Ionomycin had no effect on the expression of these genes. Pretreatment of the cells with PMA resulted in a decrease in basal c-jun expression, but did not alter the PTH-mediated increase in c-fos, c-jun, or matrix metalloproteinase-1 mRNAs.(ABSTRACT TRUNCATED AT 250 WORDS).

  1. 论蔡元培的传记写作%On Cai Yuanpei' s Biographical Writing

    Institute of Scientific and Technical Information of China (English)

    赖勤芳

    2012-01-01

    Cai Yuanpei wrote a great many biographical writings in his life though he wasn' t famous for writing biography. In the period of his formative education and studying freely, he accumulated the attainment of biographical writing and cultivated gradually the sense of cultural identification based on Chinese ancient bi- ography. When embarking on political revolution and educational innovation, he became more active in bio- graphical writing, especially choosing those revolutionaries, relatives and friends as leading characters. In his later years, he wrote autobiography with a style of annals suggested by Hu Shi. All in all, it was very obvious that Cai should be a helpful promotion to modem transformation of Chinese biographical idea though he wasn' t determined biographical writer and researcher, including his lack of more profound biographical theories and very self-conscious sense of modem biographical style.%蔡元培并不是一位以写作传记而闻名的文学家,但在一生中写下了大量的传记作品。在接受启蒙教育和“自由”读书的过程中,他积累了良好的传记写作素养,逐渐形成了对中国传记文化的认同感。随着政治革命、教育革新等活动的展开,他更是积极写作各种人物传记,其中的革命家传和亲友传最具特色。晚年在胡适的影响下用年谱体写作自传。尽管蔡元培的志向并不在传记写作及研究上,此外亦无十分深刻的传记理论见解和非常自觉的现代传记文体意识,但对中国传记文学观念的现代转型具有一定的助推作用。

  2. 基于Delphi的制图课件设计%Engineering Graphics CAI Design Based on Delphi

    Institute of Scientific and Technical Information of China (English)

    蒋先刚; 钟化兰; 涂晓斌

    2001-01-01

    Introduces programming technologies and methods of EngineeringGraphics CAI design based on Delphi, it focus on system configuration and software methods. It also presents methods and skills of using TTreeView component to construct the CAI'S database.%介绍基于Delphi开发环境下的制图课件的设计技术和实现方法。重点介绍画法几何与工程制图CAI课件系统的构造和软件实现方法,提出了用Delphi中的树状显示控件构造和管理制图CAI系统中的数据库设计方法和技巧。

  3. Differential regulation of c-jun and CREB by acrolein and 4-hydroxynonenal.

    Science.gov (United States)

    Pugazhenthi, Subbiah; Phansalkar, Ketaki; Audesirk, Gerald; West, Anne; Cabell, Leigh

    2006-01-01

    In Alzheimer's disease (AD), oxidative stress-induced lipid peroxidation leads to accumulation of unsaturated aldehydes including acrolein and 4-hydroxynonenal (4HNE) in brain. In this study, we examined the effects of these lipid peroxidation products on apoptotic pathways in cultured neurons. Acrolein and 4HNE increased the levels of active phosphorylated forms of c-jun and CREB, the transcription factors that promote apoptosis and cell survival, respectively. However, they decreased the activity of CREB-dependent BDNF promoter while they increased the activity of promoters responsive to c-jun. We hypothesized that this differential regulation could be due to competition between proapoptotic c-jun and cytoprotective CREB for CBP (CREB-binding protein), a coactivator shared by several transcription factors. In support of this hypothesis, we demonstrate that the decrease of BDNF promoter activity by acrolein and 4HNE could be restored (i) by cotransfection with CBP, (ii) by cotransfection with VP 16-CREB, a constitutively active form of CREB that does not depend on CBP for its activation, or (iii) by inhibiting JNK-mediated c-jun activation. Finally, adenoviral transduction of hippocampal neurons with VP 16-CREB resulted in significant reduction in caspase-3 activation by acrolein and 4HNE. These observations suggest that lipid peroxidation-induced differential regulation of CREB and c-jun might play a role in neurodegeneration in AD.

  4. 被历史错位的蔡襄书法%Cai Xiang's Calligraphy Dislocated by the History

    Institute of Scientific and Technical Information of China (English)

    黄志强

    2012-01-01

    宋代书法"尚意"的思潮,是一代文宗欧阳修、蔡襄和苏轼等人引领下形成的。蔡襄的书法和理论作为中国传统书法文化艺术的组成部分,具有承前启后的作用。然而在很长的历史时期里,学界在研究蔡襄的诗和书法时有"论者或不然",或认为"宋四大家"的书法是蔡京而非蔡襄等悖论。现根据史料,让我们以今人的眼光对蔡襄的书法进行整体的审视和评价。%The calligraphy in Song dynasty had the trend of "Shang Yi" under the guidance of Ouyang Xiu, Cai Xiang and Su Shi. Cai Xiang's calligraphy and theory, as one part of the traditional Chinese culture, have played an important role in linking the past and the future in Chinese calligraphy. However, there were opposite voices in the academic circles during a long time, and furthermore, Cai Jing, instead of Cai Xiang, is one of "four great calligraphers in Song dynasty", which is a fallacy in today's perspective. Now with the help of historical records, this paper gives overall review and evaluation on his works.

  5. Cais do Valongo: patrimonialização de locais, objetos e herança africana

    Directory of Open Access Journals (Sweden)

    Sandra de Sá Carneiro

    2015-12-01

    Full Text Available Resumo Neste artigo problematizamos diferentes sentidos (culturais e religiosos atribuídos ao Cais do Valongo, considerado o principal porto de entrada dos africanos escravizados no Brasil, desde que foi redescoberto nas escavações e entrou na pauta do projeto de revitalização da Zona Portuária da cidade do Rio de Janeiro. De uma “africanidade” cultural com nexos religiosos específicos, em um primeiro momento, transformou-se em símbolo da “diáspora africana”, sem que se desse destaque às referências religiosas e, depois, em uma obra realizada pelo Porto Maravilha, recuperada no processo de revitalização em curso, e lugar de promoção turística. Por último, discutimos como hoje segmentos do movimento negro e lideranças religiosas buscam manter o caráter religioso e sacralizado do Cais, promovendo ali a “Lavagem do Cais do Valongo”.

  6. Numerical Investigation Into Effect of Fuel Injection Timing on CAI/HCCI Combustion in a Four-Stroke GDI Engine

    Science.gov (United States)

    Cao, Li; Zhao, Hua; Jiang, Xi; Kalian, Navin

    2006-02-01

    The Controlled Auto-Ignition (CAI) combustion, also known as Homogeneous Charge Compression Ignition (HCCI), was achieved by trapping residuals with early exhaust valve closure in conjunction with direct injection. Multi-cycle 3D engine simulations have been carried out for parametric study on four different injection timings in order to better understand the effects of injection timings on in-cylinder mixing and CAI combustion. The full engine cycle simulation including complete gas exchange and combustion processes was carried out over several cycles in order to obtain the stable cycle for analysis. The combustion models used in the present study are the Shell auto-ignition model and the characteristic-time combustion model, which were modified to take the high level of EGR into consideration. A liquid sheet breakup spray model was used for the droplet breakup processes. The analyses show that the injection timing plays an important role in affecting the in-cylinder air/fuel mixing and mixture temperature, which in turn affects the CAI combustion and engine performance.

  7. CAI的设计与制作%CAI Design and Manufacture

    Institute of Scientific and Technical Information of China (English)

    汪岩; 汪鹰扬

    2011-01-01

    从学科教师的角度探讨多媒体CAI课件的开发思路和制作技术。发挥计算机多媒体技术的特点和优势,推动高教环境教育的发展。多媒体教学更加生动,内容更加丰富,使环境教育知识更容易被接受,多媒体课件能够用漂亮的图形界面提高使用者的学习兴趣,以丰富的声音和影片剪辑使学习更有效果。%From teachers' perspective of multimedia CAI courseware development train of thought and making technology. Play the computer multimedia technology characteristics and advantages, promote the development of environmental education in higher education. Multimedia teaching more lively, content is more rich, make environmental education knowledge more easily accepted, multimedia courseware can use beautiful graphical interface for users to improve the interest in learning, to enrich the sound and video clips to make learning be personally on the scene.

  8. I-Xe measurements of CAIs and chondrules from the CV3 chondrites Mokoia and Vigarano

    Science.gov (United States)

    Whitby, J. A.; Russell, S. S.; Turner, G.; Gilmour, J. D.

    2004-08-01

    I-Xe analyses were carried out for chondrules and refractory inclusions from the two CV3 carbonaceous chondrites Mokoia and Vigarano (representing the oxidized and reduced subgroups, respectively). Although some degree of disturbance to the I-Xe system is evident in all of the samples, evidence is preserved of aqueous alteration of CAIs in Mokoia 1 Myr later than the I-Xe age of the Shallowater standard and of the alteration of a chondrule (V3) from Vigarano ~0.7 Myr later than Shallowater. Other chondrules in Mokoia and Vigarano experienced disturbance of the I-Xe system millions of years later and, in the case of one Vigarano chondrule (VS1), complete resetting of the I-Xe system after decay of essentially all 129I, corresponding to an age more than 80 Myr after Shallowater. Our interpretation is that accretion and processing to form the Mokoia and Vigarano parent bodies must have continued for at least 4 Myr and 80 Myr, respectively. The late age of a chondrule that shows no evidence for any aqueous alteration or significant thermal processing after its formation leads us to postulate the existence of an energetic chondrule-forming mechanism at a time when nebular processes are not expected to be important.

  9. Bird community structure in riparian environments in Cai River, Rio Grande do Sul, Brazil

    Directory of Open Access Journals (Sweden)

    Jaqueline Brummelhaus

    2012-06-01

    Full Text Available Urbanization produces changes in riparian environments, causing effects in the structure of bird communities, which present different responses to the impacts. We compare species richness, abundance, and composition of birds in riparian environments with different characteristics in Cai River, Rio Grande do Sul, Brazil. We carried out observations in woodland, grassland, and urban environments, between September 2007 and August 2008. We listed 130 bird species, 29 species unique to woodland environment, and an endangeredspecies: Triclaria malachitacea. Bird abundance differed from woodland (n = 426 individuals to urban environments (n = 939 individuals (F2,6 = 7.315; P = 0.025. Species composition and feeding guilds differed significantly in the bird community structures among these three riparian environments. In the grassland and urban environments there were more generalist insectivorous species, while in the woodland environments we find more leaf and trunk insectivorous species and frugivorous species, sensitive to human impacts. Bird species can be biological quality indicators and they contribute to ecosystems performing relevant functions. With the knowledge on bird community structure and their needs, it is possible to implement management practices for restoration of degraded riparian environments.

  10. Signalling in inflammatory skin disease by AP-1 (Fos/Jun).

    Science.gov (United States)

    Uluçkan, Özge; Guinea-Viniegra, Juan; Jimenez, Maria; Wagner, Erwin F

    2015-01-01

    Skin inflammation is a physiological reaction to tissue injury, pathogen invasion and irritants. During this process, innate and/or adaptive immune cells are activated and recruited to the site of inflammation to either promote or suppress inflammation. The sequential recruitment and activation of immune cells is modulated by a combination of cytokines and chemokines, which are regulated by transcription factors, such as AP-1 (Fos/Jun), NF-κB, NFATs, and STATs. Here we review the present evidence and the underlying mechanisms of how Jun/AP-1 proteins control skin inflammation. Genetically engineered mouse models (GEMMs) in which AP-1 proteins are deleted in the epidermis have revealed that these proteins control cytokine expression at multiple levels. Constitutive epidermal deletion of JunB in mice leads to a multi-organ disease characterised by increased levels of pro-inflammatory cytokines. These JunB-deficient mutant mice display several phenotypes from skin inflammation to a G-CSF-dependent myeloproliferative disease, as well as kidney atrophy and bone loss, reminiscent of psoriasis and systemic lupus erythematosus. Importantly, epidermal deletion of both JunB and c-Jun in an inducible manner in adult mice leads to a psoriasis-like disease, in which the epidermal proteome expression profile is comparable to the one from psoriasis patient samples. In this GEMM and in psoriasis patient-derived material, S100A8/A9-dependent C3/CFB complement activation, as well as a miR-21-dependent TIMP-3/TACE pathway leading to TNF-α shedding, plays causal roles in disease development. The newly identified therapeutic targets from GEMMs together with investigations in human patient samples open up new avenues for therapeutic interventions for psoriasis and related inflammatory skin diseases.

  11. c-jun-N-Terminal Kinase (JNK) for the Treatment of Amyotrophic Lateral Sclerosis

    Science.gov (United States)

    2015-03-01

    1 AWARD NUMBER: W81XWH-12-1-0431 TITLE: “c-jun-N-Terminal Kinase (JNK) for the Treatment of Amyotrophic Lateral Sclerosis ” PRINCIPAL...TITLE AND SUBTITLE “c-jun-N-Terminal Kinase (JNK) for the Treatment of Amyotrophic Lateral Scelerosis” 5a. CONTRACT NUMBER 5b. GRANT NUMBER... Lateral   Sclerosis ”   Final  Report:  Project  Period  Sept  2012-­‐Dec  2014     Personnel  List:     Feng,  Yangbo

  12. Application of Chinese Jun-Cao technique for the production of Brazilian Ganoderma lucidum strains

    Directory of Open Access Journals (Sweden)

    Leonardo do Nascimento Rolim

    2014-06-01

    Full Text Available Ganoderma lucidum is a medicinal mushroom traditionally used in China against a wide range of diseases such as cancer and also for its prevention. In this work, commercial Chinese strains G. lucidum were compared to wild Brazilian strains aiming to determine the cultivation potential through the use of Jun-Cao. Six formulations were tested and the strains presented good response to the applied method. In general, the mixture between the grass and wood was well suited for the basidiomycetes, contributing to the preparation of substrates that generated better results in Jun Cao.

  13. Role of JunB in experimental bronchial asthma%JunB在实验性支气管哮喘中的作用

    Institute of Scientific and Technical Information of China (English)

    李海燕; 郭琦; 陈如冲; 周一平; 李明; 喻海琼; 江梅

    2013-01-01

    Objective To determine the key activator protein-1 (AP~1) subunit involved in the characteristics of the pathophysiology of asthma, in order to provide more accurate and novel molecular targets for the treatment of asthma. Methods Asthmatic rat models were employed. One hundred and thirty Wistar male rats were randomly divided into normal control, blank control, c-Jun antisense oligodeoxynucleotides (AS-ODNs), JunB AS-ODNs, JunD AS-ODNs, c-Fos AS-ODNs, FosB AS-ODNs, Fra-1 AS-ODNs, Fra-2 AS-ODNs, and nonsense ODNs groups. After gene silencing, the percentages of eosinophils (EOS) in the bronchoalveolar lavage fluid were calculated using haema-toxylin-eosin staining, and interleukin (IL)-5 mRNA was detected by reverse transcription-polymerase chain reaction (RT-PCR). Results The percentage of EOS in JunB AS-ODNs group was decreased significantly as compared with that in the blank control [(34.33±9.62)% vs (13.39±3.72)%, PO.001], but was still higher than that in the normal control [(5.61 ± 1.76)%, P=0.04]. No significant differences in the percentages of EOS between other ODNs groups and the blank control were observed (P>0.05). Compared with that in the blank control, the expression of IL5 mRNA in JunB AS-ODNs group was markedly suppressed [(0.554 2 ± 0.082 9) vs (0.822 4 ± 0.066 0), PO.001], which was also still higher than that in the normal control [(0.323 7±0.057 7), PO.001]. There were no significant differences in the expression of IL-5 mRNA between other ODNs groups and the blank control (P>0.05). Conclusion Chronic airway inflammation in asthmatic rats might depend on JunB, one of the subunits in the family of transcription factor AP-1. JunB might be a novel therapeutic target in asthma.%目的 探索激活蛋白-1 (Activator protein-1,AP-1)家族成员中参与构成哮喘病理生理特征的关键亚单位,为哮喘治疗提供更精确和新颖分子靶点.方法 建立大鼠哮喘模型.130只雄性Wistar大鼠随机分为正常对照组、哮喘

  14. Radiation-induced c-Jun activation depends on MEK1-ERK1/2 signaling pathway in microglial cells.

    Directory of Open Access Journals (Sweden)

    Zhiyong Deng

    Full Text Available Radiation-induced normal brain injury is associated with acute and/or chronic inflammatory responses, and has been a major concern in radiotherapy. Recent studies suggest that microglial activation is a potential contributor to chronic inflammatory responses following irradiation; however, the molecular mechanism underlying the response of microglia to radiation is poorly understood. c-Jun, a component of AP-1 transcription factors, potentially regulates neural cell death and neuroinflammation. We observed a rapid increase in phosphorylation of N-terminal c-Jun (on serine 63 and 73 and MAPK kinases ERK1/2, but not JNKs, in irradiated murine microglial BV2 cells. Radiation-induced c-Jun phosphorylation is dependent on the canonical MEK-ERK signaling pathway and required for both ERK1 and ERK2 function. ERK1/2 directly interact with c-Jun in vitro and in cells; meanwhile, the JNK binding domain on c-Jun is not required for its interaction with ERK kinases. Radiation-induced reactive oxygen species (ROS potentially contribute to c-Jun phosphorylation through activating the ERK pathway. Radiation stimulates c-Jun transcriptional activity and upregulates c-Jun-regulated proinflammatory genes, such as tumor necrosis factor-α, interleukin-1β, and cyclooxygenase-2. Pharmacologic blockade of the ERK signaling pathway interferes with c-Jun activity and inhibits radiation-stimulated expression of c-Jun target genes. Overall, our study reveals that the MEK-ERK1/2 signaling pathway, but not the JNK pathway, contributes to the c-Jun-dependent microglial inflammatory response following irradiation.

  15. Radiation-induced c-Jun activation depends on MEK1-ERK1/2 signaling pathway in microglial cells.

    Science.gov (United States)

    Deng, Zhiyong; Sui, Guangchao; Rosa, Paulo Mottin; Zhao, Weiling

    2012-01-01

    Radiation-induced normal brain injury is associated with acute and/or chronic inflammatory responses, and has been a major concern in radiotherapy. Recent studies suggest that microglial activation is a potential contributor to chronic inflammatory responses following irradiation; however, the molecular mechanism underlying the response of microglia to radiation is poorly understood. c-Jun, a component of AP-1 transcription factors, potentially regulates neural cell death and neuroinflammation. We observed a rapid increase in phosphorylation of N-terminal c-Jun (on serine 63 and 73) and MAPK kinases ERK1/2, but not JNKs, in irradiated murine microglial BV2 cells. Radiation-induced c-Jun phosphorylation is dependent on the canonical MEK-ERK signaling pathway and required for both ERK1 and ERK2 function. ERK1/2 directly interact with c-Jun in vitro and in cells; meanwhile, the JNK binding domain on c-Jun is not required for its interaction with ERK kinases. Radiation-induced reactive oxygen species (ROS) potentially contribute to c-Jun phosphorylation through activating the ERK pathway. Radiation stimulates c-Jun transcriptional activity and upregulates c-Jun-regulated proinflammatory genes, such as tumor necrosis factor-α, interleukin-1β, and cyclooxygenase-2. Pharmacologic blockade of the ERK signaling pathway interferes with c-Jun activity and inhibits radiation-stimulated expression of c-Jun target genes. Overall, our study reveals that the MEK-ERK1/2 signaling pathway, but not the JNK pathway, contributes to the c-Jun-dependent microglial inflammatory response following irradiation.

  16. Adipose triglyceride lipase and hormone-sensitive lipase are involved in fat loss in JunB-deficient mice.

    Science.gov (United States)

    Pinent, Montserrat; Prokesch, Andreas; Hackl, Hubert; Voshol, Peter J; Klatzer, Ariane; Walenta, Evelyn; Panzenboeck, Ute; Kenner, Lukas; Trajanoski, Zlatko; Hoefler, Gerald; Bogner-Strauss, Juliane G

    2011-07-01

    Proteins of the activator protein-1 family are known to have roles in many physiological processes such as proliferation, apoptosis, and inflammation. However, their role in fat metabolism has yet to be defined in more detail. Here we study the impact of JunB deficiency on the metabolic state of mice. JunB knockout (JunB-KO) mice show markedly decreased weight gain, reduced fat mass, and a low survival rate compared with control mice. If fed a high-fat diet, the weight gain of JunB-KO mice is comparable to control mice and the survival rate improves dramatically. Along with normal expression of adipogenic marker genes in white adipose tissue (WAT) of JunB-KO mice, this suggests that adipogenesis per se is not affected by JunB deficiency. This is supported by in vitro data, because neither JunB-silenced 3T3-L1 cells nor mouse embryonic fibroblasts from JunB-KO mice show a change in adipogenic potential. Interestingly, the key enzymes of lipolysis, adipose triglyceride lipase and hormone-sensitive lipase, were significantly increased in WAT of fasted JunB-KO mice. Concomitantly, the ratio of plasma free fatty acids per gram fat mass was increased, suggesting an elevated lipolytic rate under fasting conditions. Furthermore, up-regulation of TNFα and reduced expression of perilipin indicate that this pathway is also involved in increased lipolytic rate in these mice. Additionally, JunB-KO mice are more insulin sensitive than controls and show up-regulation of lipogenic genes in skeletal muscle, indicating a shuttling of energy substrates from WAT to skeletal muscle. In summary, this study provides valuable insights into the impact of JunB deficiency on the metabolic state of mice.

  17. Intramural optical mapping of V(m) and Ca(i)2+ during long-duration ventricular fibrillation in canine hearts.

    Science.gov (United States)

    Kong, Wei; Ideker, Raymond E; Fast, Vladimir G

    2012-03-15

    Intramural gradients of intracellular Ca(2+) (Ca(i)(2+)) Ca(i)(2+) handling, Ca(i)(2+) oscillations, and Ca(i)(2+) transient (CaT) alternans may be important in long-duration ventricular fibrillation (LDVF). However, previous studies of Ca(i)(2+) handling have been limited to recordings from the heart surface during short-duration ventricular fibrillation. To examine whether abnormalities of intramural Ca(i)(2+) handling contribute to LDVF, we measured membrane voltage (V(m)) and Ca(i)(2+) during pacing and LDVF in six perfused canine hearts using five eight-fiber optrodes. Measurements were grouped into epicardial, midwall, and endocardial layers. We found that during pacing at 350-ms cycle length, CaT duration was slightly longer (by ≃10%) in endocardial layers than in epicardial layers, whereas action potential duration (APD) exhibited no difference. Rapid pacing at 150-ms cycle length caused alternans in both APD (APD-ALT) and CaT amplitude (CaA-ALT) without significant transmural differences. For 93% of optrode recordings, CaA-ALT was transmurally concordant, whereas APD-ALT was either concordant (36%) or discordant (54%), suggesting that APD-ALT was not caused by CaA-ALT. During LDVF, V(m) and Ca(i)(2+) progressively desynchronized when not every action potential was followed by a CaT. Such desynchronization developed faster in the epicardium than in the other layers. In addition, CaT duration strongly increased (by ∼240% at 5 min of LDVF), whereas APD shortened (by ∼17%). CaT rises always followed V(m) upstrokes during pacing and LDVF. In conclusion, the fact that V(m) upstrokes always preceded CaTs indicates that spontaneous Ca(i)(2+) oscillations in the working myocardium were not likely the reason for LDVF maintenance. Strong V(m)-Ca(i)(2+) desynchronization and the occurrence of long CaTs during LDVF indicate severely impaired Ca(i)(2+) handling and may potentially contribute to LDVF maintenance.

  18. Deletion of Jun proteins in adult oligodendrocytes does not perturb cell survival, or myelin maintenance in vivo.

    Directory of Open Access Journals (Sweden)

    Bettina Schreiner

    Full Text Available Oligodendrocytes, the myelin-forming glial cells of the central nervous system (CNS, are fundamental players in rapid impulse conduction and normal axonal functions. JunB and c-Jun are DNA-binding components of the AP-1 transcription factor, which is known to regulate different processes such as proliferation, differentiation, stress responses and death in several cell types, including cultured oligodendrocyte/lineage cells. By selectively inactivating Jun B and c-Jun in myelinating oligodendrocytes in vivo, we generated mutant mice that developed normally, and within more than 12 months showed normal ageing and survival rates. In the adult CNS, absence of JunB and c-Jun from mature oligodendrocytes caused low-grade glial activation without overt signs of demyelination or secondary leukocyte infiltration into the brain. Even after exposure to toxic or autoimmune oligodendrocyte insults, signs of altered oligodendrocyte viability were mild and detectable only upon cuprizone treatment. We conclude that JunB and c-Jun expression in post-mitotic oligodendrocytes is mostly dispensable for the maintainance of white matter tracts throughout adult life, even under demyelinating conditions.

  19. CDK-mediated regulation of cell functions via c-Jun phosphorylation and AP-1 activation.

    Directory of Open Access Journals (Sweden)

    Tony J Vanden Bush

    Full Text Available Cyclin-dependent kinases (CDKs and their targets have been primarily associated with regulation of cell-cycle progression. Here we identify c-Jun, a transcription factor involved in the regulation of a broad spectrum of cellular functions, as a newly recognized CDK substrate. Using immune cells from mouse and human, and several complementary in vitro and in vivo approaches including dominant negative protein expression, pharmacologic inhibitors, kinase assays and CDK4 deficient cells, we demonstrate the ability of CDK4 to phosphorylate c-Jun. Additionally, the activity of AP-1, a ubiquitous transcription factor containing phosphorylated c-Jun as a subunit, was inhibited by abrogating CDK4. Surprisingly, the regulation of c-Jun phosphorylation by CDK4 occurred in non-dividing cells, indicating that this pathway is utilized for cell functions that are independent of proliferation. Our studies identify a new substrate for CDK4 and suggest a mechanism by which CDKs can regulate multiple cellular activation functions, not all of which are directly associated with cell cycle progression. These findings point to additional roles of CDKs in cell signaling and reveal potential implications for therapeutic manipulations of this kinase pathway.

  20. Caspase-2 is essential for c-Jun transcriptional activation and Bim induction in neuron death

    Science.gov (United States)

    Jean, Ying Y.; Ribe, Elena M.; Pero, Maria Elena; Moskalenko, Marina; Iqbal, Zarah; Marks, Lianna J.; Greene, Lloyd A.; Troy, Carol M.

    2014-01-01

    SYNOPSIS Neuronal apoptotic death generally requires de novo transcription, and activation of the transcription factor c-Jun has been shown to be necessary in multiple neuronal death paradigms. Caspase-2 has been implicated in death of neuronal and non-neuronal cells, but its relationship to transcriptional activation has not been clearly elucidated. Here, using two different neuronal apoptotic paradigms, β-amyloid treatment and NGF withdrawal, we examined the hierarchical role of caspase-2 activation in the transcriptional control of neuron death. Both paradigms induce rapid activation of caspase-2 as well as activation of the transcription factor c-Jun and subsequent induction of the pro-apoptotic BH-3 only protein Bim. Caspase-2 activation is dependent on the adaptor protein RAIDD, and both caspase-2 and RAIDD are required for c-Jun activation and Bim induction. Our work, thus, shows that rapid caspase-2 activation is essential for c-Jun activation and Bim induction in neurons subjected to apoptotic stimuli. This places caspase-2 at an apical position in the apoptotic cascade and demonstrates for the first time that caspase-2 can regulate transcription. PMID:23815625

  1. Pancreatic β-cells activate a JunB/ATF3-dependent survival pathway during inflammation

    DEFF Research Database (Denmark)

    Gurzov, E N; Barthson, J; Marhfour, I

    2012-01-01

    Destruction of insulin-producing pancreatic β-cells by local autoimmune inflammation is a hallmark of type 1 diabetes. Histochemical analysis of pancreases from non-obese diabetic mice indicated activation of the transcription factor JunB/AP-1 (activator protein-1) after autoimmune infiltration o...

  2. Yun Zhong Jun and Da Si Ming(Deity of Clouds and Great Master of Fate)

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Artistic Value: Yun Zhong Jun and Da Si tiling was created in 1954. Fu Baoshi started painting figures after his relocation to Sichuan Province in the 1930Sl He was less prolific in this genre than in landscapes, but nevertheless developed and retained a distinctive style,Extensively cultured in Chinese history and dassical iterature,

  3. Evidence for an early nitrogen isotopic evolution in the solar nebula from volatile analyses of a CAI from the CV3 chondrite NWA 8616

    Science.gov (United States)

    Füri, Evelyn; Chaussidon, Marc; Marty, Bernard

    2015-03-01

    Nitrogen and noble gas (Ne-Ar) abundances and isotope ratios, determined by CO2 laser extraction static mass spectrometry analysis, as well as Al-Mg and O isotope data from secondary ion mass spectrometry (SIMS) analyses, are reported for a type B calcium-aluminum-rich inclusion (CAI) from the CV3 chondrite NWA 8616. The high (26Al/27Al)i ratio of (5.06 ± 0.50) × 10-5 dates the last melting event of the CAI at 39-99+109ka after "time zero", limiting the period during which high-temperature exchanges between the CAI and the nebular gas could have occurred to a very short time interval. Partial isotopic exchange with a 16O-poor reservoir resulted in Δ17O > -5‰ for melilite and anorthite, whereas spinel and Al-Ti-pyroxene retain the inferred original 16O-rich signature of the solar nebula (Δ17O ⩽ -20‰). The low 20Ne/22Ne (⩽0.83) and 36Ar/38Ar (⩽0.75) ratios of the CAI rule out the presence of any trapped planetary or solar noble gases. Cosmogenic 21Ne and 38Ar abundances are consistent with a cosmic ray exposure (CRE) age of ∼14 to 20 Ma, assuming CR fluxes similar to modern ones, without any evidence for pre-irradiation of the CAI before incorporation into the meteorite parent body. Strikingly, the CAI contains 1.4-3.4 ppm N with a δ15N value of +8‰ to +30‰. Even after correcting the measured δ15N values for cosmogenic 15N produced in situ, the CAI is highly enriched in 15N compared to the protosolar nebula (δ15NPSN = -383 ± 8‰; Marty et al., 2011), implying that the CAI-forming region was contaminated by 15N-rich material within the first 0.15 Ma of Solar System history, or, alternatively, that the CAI was ejected into the outer Solar System where it interacted with a 15N-rich reservoir.

  4. A gravidade do trauma em vítimas de traumatismo crânio-encefálico avaliada pelo manual AIS/90 e mapas CAIS/85 La gravedad del trauma en víctimas de traumatismo cráneo-encefálico por medio del manual AIS/90 y mapas CAIS/85 Injury severity measures by AIS/90 manual and CAIS/85 chart in head injured patients

    Directory of Open Access Journals (Sweden)

    Regina Marcia Cardoso de Sousa

    1998-01-01

    Full Text Available Estudo comparativo do uso do manual da ABBREVIATED INJURY SCALE (AIS e dos mapas da CONDENSED ABBREVIATED INJURY SCALE (CAIS, como bases para cálculo do INJURY SEVERITY SCORE (ISS em vítimas de trauma crânio-encefálico. Os resultados evidenciaram que o valor do ISS foi coincidente na maioria (59,51% das vítimas passíveis de codificação pelos dois instrumentos. Quanto à indicação da faixa de gravidade do trauma (grave, moderado e leve não existiram diferenças estatisticamente significantes entre os dois instrumentos. Quanto a capacidade de cobertura da CAIS/85 para a identificação da gravidade das lesões constatou-se que a CAIS/85 permitiu a pontuação de 61,38% das lesões pontuadas com a AIS/90.Estudio comparativo del uso del Manual de la ABBREVIATED INJURY SCALE (AIS y de los mapas de la CONDENSED ABBREVIATED INJURY SCALE (CAIS, como base para el cálculo del INJURY SEVERITY SCORE (ISS en víctimas de trauma cráneo-encefálico. Los resultados mostraron que el valor del ISS coincidía en la mayoría (58,51% de las víctimas posibles de codificación por los dos instrumentos. En cuanto a la indicación de la faja de gravedad del trauma (grave, moderado y leve no existian diferencias estadísticamente significantes entre los dos instrumentos. En cuanto a la capacidad de cobertura de la CAIS/85 para la identificación de la gravedad de las lesiones, se constató que la CAIS/85 permitió la puntuación de 61,38% de las lesiones puntiadas con la AIS/90.This study was developed in order to compare the use of the ABBREVIATED INJURY SCALE (AIS and the CONDENSED ABBREVIATED INJURY SCALE (CAIS as basis to calculate INJURY SEVERITY SCORE (ISS in head injured patients. The results showed that the ISS value was equivalent in the majority of the patients (58,51% codified by both scales. Also no statistic differences between the scales were perceived when we compared the severity levels as severe, moderate and minor. 61,38% of the lesions

  5. A revista Cais entre o protagonismo e o assistencialismo: Uma análise discursiva crítica

    Directory of Open Access Journals (Sweden)

    Viviane de Melo Resende

    2012-10-01

    Full Text Available Como parte dos resultados de um projeto integrado cujo escopo é investigar, por meio de análises discursivas, as práticas envolvidas na produção e na distribuição de cinco publicações em língua portuguesa voltadas para a situação de rua, este artigo focaliza, com base na Análise de Discurso Crítica, a revista Cais, publicada em Lisboa. Configurando‑se como jornal de rua, a revista é vendida na rua e por pessoas em situação de rua ou de risco, para as quais revertem 70% da venda de cada exemplar. Mais que um meio de comunicação e difusão de problemas sociais, acredita‑se que esse tipo de imprensa proporciona a configuração de posições e relações diferentes, podendo por isso alterar a experiência da exclusão. Neste artigo, tomando como dados excertos de uma entrevista com o seu editor, exploro em que medida se dá a participação de pessoas em situação de rua na produção da revista Cais e na representação desta mesma situação.

  6. Design of CAI Courseware Based on Virtual Reality Mechanism%基于VR机制的CAI课件设计

    Institute of Scientific and Technical Information of China (English)

    管群

    2001-01-01

    In this paper,the application feature and significance of VR technology in the educational field are summarized.In particular,the design mechanism of CAI courseware of the instruction aiming at individuals is studied,and with virtual reality mechanism a learning-while-doing environment is realized for the user in the CAI courseware in the major of the computer application.The design theory,the technique way,some of the algorithm flowchart and the interface of the exercise of operation are given.%论述了虚拟现实技术在教育领域中的应用特点和重要意义。特别研究了针对个别化教学的CAI课件设计机制,并运用虚拟现实机制在计算机应用类CAI课件设计中实现了一个可供用户边学边做的学习环境。给出了设计原理、技术路线、部分算法流程和操作练习界面。

  7. Alterações da junção neuromuscular em miopatias experimentais no camundongo

    OpenAIRE

    Luiz Fernando Bleggi Torres

    1989-01-01

    As alterações morfológicas observadas em junção neuromuscular de dois modelos de miopatia em camundongos são estudadas por métodos histoquímicos para demonstrar atividade da enzima acetilcolinesterase e por microscopia eletrônica. Em ambas as situações os resultados obtidos são similares, indicando que a junção neuromuscular permanece intacta mesmo quando a fibra que inerva está sofrendo necrose. Em fibras musculares regeneradas há acentuada simplificação das pregas pós-sinápticas, com reduçã...

  8. John F. Simon, jr. / John F. jun. Simon ; interv. Tilman Baumgärtel

    Index Scriptorium Estoniae

    Simon, John F. jun.

    2006-01-01

    Ameerika kunstnikust-programmeerijast Jon F. Simon juuniorist (sünd. 1963), tema loomingust, vestlus kunstnikuga 19. 12. 1999. a. tema ateljees. J. F. Simon jun.-i teosed on tarkvara. Monitoril tekkinud kujutisi on kunstnik eksponeerinud nimetuse "Panels" all. Kunstniku joonistusprogrammist, arvutiprogrammist "Every Icon", mis asub Internetis, tööst "Combination", võrgutööst "Alter Stars" (1995-1998) ja muust

  9. Cytogenetic characterization of Caesalpinia spinosafrom Tarma and Palca (Junín

    Directory of Open Access Journals (Sweden)

    Alberto López

    2014-03-01

    Full Text Available Somatic chromosomes of Caesalpinia spinosa (Feuillée ex Molina Kuntze, “Tara”, wild populations of Huinco and Palca (Junín regions were studied. The specie were diploid (2n=24. Chromosomes were small. The karyotypes showed the same chromosome number, they found differences in morphological parameters of the same, with the karyotype formula for the town of Huinco: 6m + 6 sm and the town of Palca: 5m + 7 sm.

  10. John F. Simon, jr. / John F. jun. Simon ; interv. Tilman Baumgärtel

    Index Scriptorium Estoniae

    Simon, John F. jun.

    2006-01-01

    Ameerika kunstnikust-programmeerijast Jon F. Simon juuniorist (sünd. 1963), tema loomingust, vestlus kunstnikuga 19. 12. 1999. a. tema ateljees. J. F. Simon jun.-i teosed on tarkvara. Monitoril tekkinud kujutisi on kunstnik eksponeerinud nimetuse "Panels" all. Kunstniku joonistusprogrammist, arvutiprogrammist "Every Icon", mis asub Internetis, tööst "Combination", võrgutööst "Alter Stars" (1995-1998) ja muust

  11. Activator protein 1 (Fos/Jun) functions in inflammatory bone and skin disease.

    Science.gov (United States)

    Zenz, Rainer; Eferl, Robert; Scheinecker, Clemens; Redlich, Kurt; Smolen, Josef; Schonthaler, Helia B; Kenner, Lukas; Tschachler, Erwin; Wagner, Erwin F

    2008-01-01

    Activator protein 1 (AP-1) (Fos/Jun) is a transcriptional regulator composed of members of the Fos and Jun families of DNA binding proteins. The functions of AP-1 were initially studied in mouse development as well as in the whole organism through conventional transgenic approaches, but also by gene targeting using knockout strategies. The importance of AP-1 proteins in disease pathways including the inflammatory response became fully apparent through conditional mutagenesis in mice, in particular when employing gene inactivation in a tissue-specific and inducible fashion. Besides the well-documented roles of Fos and Jun proteins in oncogenesis, where these genes can function both as tumor promoters or tumor suppressors, AP-1 proteins are being recognized as regulators of bone and immune cells, a research area termed osteoimmunology. In the present article, we review recent data regarding the functions of AP-1 as a regulator of cytokine expression and an important modulator in inflammatory diseases such as rheumatoid arthritis, psoriasis and psoriatic arthritis. These new data provide a better molecular understanding of disease pathways and should pave the road for the discovery of new targets for therapeutic applications.

  12. Modelling the mechanism of GR/c-Jun/Erg crosstalk in apoptosis of acute lymphoblastic leukaemia

    Directory of Open Access Journals (Sweden)

    Daphne eChen

    2012-11-01

    Full Text Available Acute lymphoblastic leukaemia (ALL is one of the most common forms of malignancy that occurs in lymphoid progenitor cells, particularly in children. Synthetic steroid hormones glucocorticoids (GCs are widely used as part of the ALL treatment regimens due to their apoptotic function, but their use also brings about various side effects and drug resistance. The identification of the molecular differences between the GCs responsive and resistant cells therefore are essential to decipher such complexity and can be used to improve therapy. However, the emerging picture is complicated as the activities of genes and proteins involved are controlled by multiple factors. By adapting the systems biology framework to address this issue, we here integrated the available knowledge together with experimental data via the building of a series of mathematical models. This rationale enabled us to unravel molecular interactions involving c-Jun in GC induced apoptosis and identify Erg as determinant for GC resistance. The results revealed an alternative potential mechanism where c-Jun may be an indirect GR target that is controlled via an upstream repressor protein. The models also highlight the importance of Erg for GR function, particularly in GC sensitive C7 cells where Erg directly regulates GR in agreement with our previous experimental results. Our models describe potential GR-controlled molecular mechanisms of c-Jun/Bim and Erg regulation. We also demonstrate the importance of using a systematic approach to translate human disease processes into computational models in order to derive information-driven new hypotheses.

  13. JUN dependency in distinct early and late BRAF inhibition adaptation states of melanoma

    Science.gov (United States)

    Titz, Bjoern; Lomova, Anastasia; Le, Allison; Hugo, Willy; Kong, Xiangju; ten Hoeve, Johanna; Friedman, Michael; Shi, Hubing; Moriceau, Gatien; Song, Chunying; Hong, Aayoung; Atefi, Mohammad; Li, Richard; Komisopoulou, Evangelia; Ribas, Antoni; Lo, Roger S; Graeber, Thomas G

    2016-01-01

    A prominent mechanism of acquired resistance to BRAF inhibitors in BRAFV600-mutant melanoma is associated with the upregulation of receptor tyrosine kinases. Evidences suggested that this resistance mechanism is part of a more complex cellular adaptation process. Using an integrative strategy, we found this mechanism to invoke extensive transcriptomic, (phospho-) proteomic and phenotypic alterations that accompany a cellular transition to a de-differentiated, mesenchymal and invasive state. Even short-term BRAF-inhibitor exposure leads to an early adaptive, differentiation state change—characterized by a slow-cycling, persistent state. The early persistent state is distinct from the late proliferative, resistant state. However, both differentiation states share common signaling alterations including JUN upregulation. Motivated by the similarities, we found that co-targeting of BRAF and JUN is synergistic in killing fully resistant cells; and when used up-front, co-targeting substantially impairs the formation of the persistent subpopulation. We confirmed that JUN upregulation is a common response to BRAF inhibitor treatment in clinically treated patient tumors. Our findings demonstrate that events shared between early- and late-adaptation states provide candidate up-front co-treatment targets. PMID:27648299

  14. Modeling the Mechanism of GR/c-Jun/Erg Crosstalk in Apoptosis of Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    Chen, Daphne Wei-Chen; Krstic-Demonacos, Marija; Schwartz, Jean-Marc

    2012-01-01

    Acute lymphoblastic leukemia (ALL) is one of the most common forms of malignancy that occurs in lymphoid progenitor cells, particularly in children. Synthetic steroid hormones glucocorticoids (GCs) are widely used as part of the ALL treatment regimens due to their apoptotic function, but their use also brings about various side effects and drug resistance. The identification of the molecular differences between the GCs responsive and resistant cells therefore are essential to decipher such complexity and can be used to improve therapy. However, the emerging picture is complicated as the activities of genes and proteins involved are controlled by multiple factors. By adopting the systems biology framework to address this issue, we here integrated the available knowledge together with experimental data by building a series of mathematical models. This rationale enabled us to unravel molecular interactions involving c-Jun in GC induced apoptosis and identify Ets-related gene (Erg) as potential biomarker of GC resistance. The results revealed an alternative possible mechanism where c-Jun may be an indirect GR target that is controlled via an upstream repressor protein. The models also highlight the importance of Erg for GR function, particularly in GC sensitive C7 cells where Erg directly regulates GR in agreement with our previous experimental results. Our models describe potential GR-controlled molecular mechanisms of c-Jun/Bim and Erg regulation. We also demonstrate the importance of using a systematic approach to translate human disease processes into computational models in order to derive information-driven new hypotheses.

  15. Jun N-Terminal Kinase 1 Mediates Transcriptional Induction of Matrix Metal loproteinase 9 Expression

    Directory of Open Access Journals (Sweden)

    David L. Crowe

    2001-01-01

    Full Text Available Tumor cell invasion and metastasis require precise coordination of adherence to extracellular matrix (ECM and controlled degradation of its components. Invasive cells secrete proteolytic enzymes known as matrix metal lop roteinases (MMPs which degrade specific basement membrane molecules. Expression of these enzymes is regulated by multiple signaling mechanisms, including the mitogen-activated protein kinase (MAPK pathway. One of the terminal effectors of this signaling cascade is jun N-terminal kinase 1 (JNK1 which phosphorylates the transcription factor c-jun, a component of the AP-1 complex. MMP-9 expression is regulated by two well-characterized AP-1 sites in the promoter of this gene. To determine how JNK1 activity regulated MMP-9 expression in human squamous cell carcinoma lines, we overexpressed this kinase in SCC25 cells. JNK1 overexpression induced MMP-9 protein levels and activity in this cell line. Elevated MMP-9 expression correlated with increased invasion of reconstituted basement membranes by JNK1 -overexpressiog clones. Site-directed mutagenesis of the MMP-9 promoter revealed that JNK1 cooperated with its transcription factor target c-jun to increase MMP-9 expression at the transcriptional level via the proximal AP-1 site. These results suggest that elevated JNK1 expression may contribute to increased MMP-9 activity and ECM invasion by tumor cells.

  16. Alterações da junção neuromuscular em miopatias experimentais no camundongo

    Directory of Open Access Journals (Sweden)

    Luiz Fernando Bleggi Torres

    1989-06-01

    Full Text Available As alterações morfológicas observadas em junção neuromuscular de dois modelos de miopatia em camundongos são estudadas por métodos histoquímicos para demonstrar atividade da enzima acetilcolinesterase e por microscopia eletrônica. Em ambas as situações os resultados obtidos são similares, indicando que a junção neuromuscular permanece intacta mesmo quando a fibra que inerva está sofrendo necrose. Em fibras musculares regeneradas há acentuada simplificação das pregas pós-sinápticas, com redução de até 50% dos valores normais, comprovado por estudos morfométricos. A ausência de repercussões fisiológicas ou clínicas detectáveis nesses modelos, apesar da significativa hipotrofia da membrana pós-sináptica, sugere que a exuberante quantidade de pregas pós-sinápticas normalmente encontradas nas junções mioneürais pode representar mecanismo anatômico de segurança na transmissão química neuromuscular.

  17. Calcium-aluminum-rich inclusions with fractionation and unidentified nuclear effects (FUN CAIs): II. Heterogeneities of magnesium isotopes and 26Al in the early Solar System inferred from in situ high-precision magnesium-isotope measurements

    Science.gov (United States)

    Park, Changkun; Nagashima, Kazuhide; Krot, Alexander N.; Huss, Gary R.; Davis, Andrew M.; Bizzarro, Martin

    2017-03-01

    Calcium-aluminum-rich inclusions with isotopic mass fractionation effects and unidentified nuclear isotopic anomalies (FUN CAIs) have been studied for more than 40 years, but their origins remain enigmatic. Here we report in situ high precision measurements of aluminum-magnesium isotope systematics of FUN CAIs by secondary ion mass spectrometry (SIMS). Individual minerals were analyzed in six FUN CAIs from the oxidized CV3 carbonaceous chondrites Axtell (compact Type A CAI Axtell 2271) and Allende (Type B CAIs C1 and EK1-4-1, and forsterite-bearing Type B CAIs BG82DH8, CG-14, and TE). Most of these CAIs show evidence for excess 26Mg due to the decay of 26Al. The inferred initial 26Al/27Al ratios [(26Al/27Al)0] and the initial magnesium isotopic compositions (δ26Mg0) calculated using an exponential law with an exponent β of 0.5128 are (3.1 ± 1.6) × 10-6 and 0.60 ± 0.10‰ (Axtell 2271), (3.7 ± 1.5) × 10-6 and -0.20 ± 0.05‰ (BG82DH8), (2.2 ± 1.1) × 10-6 and -0.18 ± 0.05‰ (C1), (2.3 ± 2.4) × 10-5 and -2.23 ± 0.37‰ (EK1-4-1), (1.5 ± 1.1) × 10-5 and -0.42 ± 0.08‰ (CG-14), and (5.3 ± 0.9) × 10-5 and -0.05 ± 0.08‰ (TE) with 2σ uncertainties. We infer that FUN CAIs recorded heterogeneities of magnesium isotopes and 26Al in the CAI-forming region(s). Comparison of 26Al-26Mg systematics, stable isotope (oxygen, magnesium, calcium, and titanium) and trace element studies of FUN and non-FUN igneous CAIs indicates that there is a continuum among these CAI types. Based on these observations and evaporation experiments on CAI-like melts, we propose a generic scenario for the origin of igneous (FUN and non-FUN) CAIs: (i) condensation of isotopically normal solids in an 16O-rich gas of approximately solar composition; (ii) formation of CAI precursors by aggregation of these solids together with variable abundances of isotopically anomalous grains-possible carriers of unidentified nuclear (UN) effects; and (iii) melt evaporation of these precursors

  18. Toward functional analysis of protein interactome using "in vitro virus": in silico analyses of Fos/Jun interactors.

    Science.gov (United States)

    Miyamoto-Sato, Etsuko; Yanagawa, Hiroshi

    2006-01-01

    Our high-throughput in vitro virus (IVV) method for selection of protein-protein interactions (PPI) and complexes, based on a simple cell-free co-translation and selection followed by computational sequence data analysis, was previously used to identify 31 Fos and Jun interactors. Here, in silico analyses of biological function, localization and phenotype of these AP-1 (Fos/Jun) interactors were performed. The results suggest that Fos and Jun do not necessarily work together, but also interact separately with novel interactors, including products of disease-related genes. Fos showed transcription-related activities, while Jun interacted with motor-related and structural proteins. The reliability of the IVV selection for the Fos interactors was further confirmed by means of in vitro reciprocal prey and bait protein experiments and co-immunoprecipitation. Further study of these novel interactors may provide clues to new pathways or mechanisms of biological functions and diseases.

  19. Identification of a c-Jun homolog from Litopenaeus vannamei as a downstream substrate of JNK in response to WSSV infection.

    Science.gov (United States)

    Yao, Defu; Ruan, Lingwei; Xu, Xun; Shi, Hong

    2015-04-01

    c-Jun, a major substrate of c-Jun N-terminal kinase (JNK), participates in regulating gene transcription in response to various stimuli, including cytokines, stress signals, bacterial and viral infection. Results from our previous studies suggested that Litopenaeus vannamei JNK (LvJNK) could be utilized by white spot syndrome virus (WSSV) to facilitate viral replication and gene expression. In this article, a c-Jun homolog from Litopenaeus vannamei (designated as Lvc-Jun) was cloned and its role in WSSV infection was studied. Sequence analysis displayed that Lvc-Jun was a novel homolog of c-Jun family, which contained characteristic Jun and basic leucine zipper (bZIP) domains, and two conserved serine phosphorylation sites (Ser49/59). Semi-quantitative RT-PCR analysis showed that Lvc-Jun mRNAs were expressed in all examined tissues. Further investigation determined that Lvc-Jun was located in the nucleus through self-interaction and its phosphorylation levels could be reduced by JNK inhibitor, suggesting that Lvc-Jun could be regulated by LvJNK through phosphorylation and function as a transcription regulator in a homodimer. During the process of WSSV infection, the transcription levels of Lvc-Jun were up-regulated associating with the raising expression and phosphorylation levels of its protein. Moreover, TPA (12-O-tetradecanoylphorbol-13-acetate), a potent inducer of c-Jun, could remarkably promote viral immediate-early gene wsv069 transcription in crayfish hemocytes. Conclusively, our results provided experimental evidences that Lvc-Jun was engaged in WSSV infection and further implied that JNK-c-Jun signaling pathway might be important for WSSV replication and viral gene expression.

  20. c-Jun, Fra-2, and ATF-2 immunoreactivity in the jejunal tissues of the healthy rat.

    Science.gov (United States)

    Keklikoglu, Nurullah

    2008-10-01

    The aim of this study was to compare the localization of some activator protein-1 (AP-1) proteins in healthy rat jejunum. For this purpose, the AP-1 members c-Jun, Fra-2, and ATF-2 immunoreactivity (c-Jun-IR, Fra-2-IR, ATF-2-IR) in villus epithelial cells (ECs), intravillous lamina propria cells (LPCs), crypt cells (CCs), and smooth muscle cells (SMCs) were analyzed by immunohistochemical methods. Among all the cell groups, the lowest positivity ratio was found in c-Jun-IR and the highest positivity ratio was found in ATF-2-IR. For each group of ECs, LPCs, CCs, and SMCs, c-Jun-IR, Fra-2-IR, and ATF-2-IR were compared and statistically significant differences found. There were no significant differences among the cell groups with respect to c-Jun-IR and Fra-2-IR, but there was a statistically significant difference in ATF-2-IR. These findings suggest that each member of AP-1 is expressed differently and that ATF-2 is more active than c-Jun and Fra-2 in physiological conditions in healthy rat jejunum.

  1. HP1a/KDM4A is involved in the autoregulatory loop of the oncogene gene c-Jun.

    Science.gov (United States)

    Liu, Yan; Zhang, Daoyong

    2015-01-01

    The proto-oncogene c-Jun plays crucial roles in tumorigenesis, and its aberrant expression has been implicated in many cancers. Previous studies have shown that the c-Jun gene is positively autoregulated by its product. Notably, it has also been reported that c-Jun proteins are enriched in its gene body region. However, the role of c-Jun proteins in its gene body region has yet to be uncovered. HP1a is an evolutionarily conserved heterochromatin-associated protein, which plays an essential role in heterochromatin-mediated gene silencing. Interestingly, accumulating evidence shows that HP1a is also localized to euchromatic regions to positively regulate gene transcription. However, the underlying mechanism has not been defined. In this study, we demonstrate that HP1a is involved in the positive autoregulatory loop of the Jra gene, the c-Jun homolog in Drosophila. Jra recruits the HP1a/KDM4A complex to its gene body region upon osmotic stress to reduce H3K36 methylation levels and disrupt H3K36 methylation-dependent histone deacetylation, resulting in high levels of histone acetylation in the Jra gene body region, thus promoting gene transcription. These results not only expand our knowledge toward the mechanism of c-Jun regulation, but also reveal the mechanism by which HP1a exerts its positive regulatory function in gene expression.

  2. Ensiled and dry cassava leaves, and sweet potato vines as a protein source in diets for growing Vietnamese large white Mong Cai pigs

    NARCIS (Netherlands)

    Nguyen, T.H.L.; Le, N.G.; Verstegen, M.W.A.; Hendriks, W.H.

    2010-01-01

    The aim of the present study was to evaluate the effects of replacing 70% of the protein from fish meal by protein from ensiled or dry cassava leaves and sweet potato vines on the performance and carcass characters of growing F1 (Large White¿Mong Cai) pigs in Central Vietnam. Twenty-five crossbred

  3. Design of Bilingual Teaching CAI Courseware in Human Parasitology Courses%人体寄生虫学课程双语教学CAI课件的研制

    Institute of Scientific and Technical Information of China (English)

    曾瑾; 王红; 李翠英; 杨立军; 王文林

    2012-01-01

    目的 研制和开发一套有云南地域特色的人体寄生虫学课程双语教学CAI课件.方法 以PowerPoint 为平台,用Authorware、Flash、Photoshop、Audition、Gif Animator 等软件为辅助工具进行CAI课件制作.结果 制作了含有医学蠕虫学、医学原虫学和医学节肢动物学三部分内容组成的双语教学CAI课件.结论 脚本设计和各类软件的综合应用是CAI课件研制的关键.%Objective To design and develop a set of bilingual CAI coursewares especially adapted to teach human parasitology in Yunnan Province. Method The CAI coursewares were designed using PowerPoint as the main platform, assisted with the incorporation of softwares such as Authorware, Flash, Photoshop, Audition and Gif Animator. Result A set of bilingual CAI Courseware to teach Human Parasitology including medical helminthology, medical protozoology and medical arthropodology has been developed. Conclusion Script design and comprehensive application of variable softwares are the key points in designing and developing CAI coursewares.

  4. Ensiled and dry cassava leaves, and sweet potato vines as a protein source in diets for growing Vietnamese large white Mong Cai pigs

    NARCIS (Netherlands)

    Nguyen, T.H.L.; Le, N.G.; Verstegen, M.W.A.; Hendriks, W.H.

    2010-01-01

    The aim of the present study was to evaluate the effects of replacing 70% of the protein from fish meal by protein from ensiled or dry cassava leaves and sweet potato vines on the performance and carcass characters of growing F1 (Large White¿Mong Cai) pigs in Central Vietnam. Twenty-five crossbred p

  5. Perceptions on hospitality when visiting secluded communities of guaranis, caiçaras e quilombolas in Paraty region

    Directory of Open Access Journals (Sweden)

    Luis Alberto Beares

    2008-10-01

    Full Text Available Tourism in secluded communities puts different cultures in contact with each other and must be handled carefully not to cause environmental damage as well as cultural loss which might jeopardize the local development and create hostile relationships. The proposal of in sito tourism, considering the local memory and patrimony as a hospitality potential, was observed during technical visitations to three communities located in the Paraty region and surroundings: Guarani, Caiçara (fishermen and Quilombola(African slaves descendants. Through field work involving visitations to communities and interviews with locals, information regarding cultural differences and the importance of the land occupation in the history of each of the communities was assessed. The common link in the history of these peoples is the struggle for the right of land possession. During visits when people shared their territory various forms of hospitality in each community were verified, issued from different cultures and cultural values.

  6. Chronological study of oxygen isotope composition for the solar protoplanetary disk recorded in a fluffy Type A CAI from Vigarano

    Science.gov (United States)

    Kawasaki, Noriyuki; Itoh, Shoichi; Sakamoto, Naoya; Yurimoto, Hisayoshi

    2017-03-01

    Fluffy Type A Ca-Al-rich inclusions (CAIs) containing reversely zoned melilite crystals are suggested to be aggregates of direct condensates from solar nebular gas. We conducted an investigation of 26Al-26Mg systematics of a fluffy Type A CAI from Vigarano, named V2-01, with known oxygen isotopic distributions of reversely zoned melilite crystals; we also conducted oxygen isotope measurements of coexisting minerals. Two of six reversely zoned melilite crystals show continuous variations in magnesium isotopic composition, with δ25Mg decreasing along the inferred direction of crystal growth, which supports the idea that they originated through condensation. Petrography suggests that the constituent minerals of V2-01 formed in the following order: first spinel and fassaite enclosed by melilite, then reversely zoned melilite crystals, and spinel and diopside in the Wark-Lovering rim. The spinel enclosed by melilite has 16O-rich compositions (Δ17O ∼ -24‰) and on an Al-Mg evolutionary diagram plots along model isochron with an initial value of (26Al/27Al)0 = (5.6 ± 0.2) × 10-5. The fassaite enclosed by melilite crystals shows variable oxygen isotopic compositions (Δ17O ∼ -12‰ and -17‰) and plots on an isochron with (26Al/27Al)0 = (5.6 ± 0.2) × 10-5. The oxygen isotopic compositions of reversely zoned melilite showed continuous variations in Δ17O along the inferred direction of crystal growth, suggesting that surrounding nebular gas, during the formation of the reversely zoned melilite, changed from 16O-poor (Δ17O values larger than -10‰) to 16O-rich (Δ17O ∼ -25‰). The six reversely zoned melilite crystals show indistinguishable initial 26Al/27Al values with an average (26Al/27Al)0 of (4.7 ± 0.3) × 10-5, which is clearly distinguishable from the value of enclosed spinel and fassaite, indicating a younger formation age than the enclosed spinel and fassaite. The spinel and diopside from the Wark-Lovering rim show 16O-rich compositions (Δ17O

  7. MAGE-A1 promotes melanoma proliferation and migration through C-JUN activation

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Dong [Department of Dermatology, General Hospital of People' s Liberation Army, Beijing 100853 (China); The 309th Hospital of China People' s Liberation Army, Beijing 100091 (China); Wang, Junyun; Ding, Nan [CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101 (China); University of Chinese Academy of Sciences, Beijing 100049 (China); Li, Yongjun; Yang, Yaran [CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101 (China); Fang, Xiangdong, E-mail: fangxd@big.ac.cn [CAS Key Laboratory of Genome Sciences and Information, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101 (China); Zhao, Hua, E-mail: luckhua301@163.com [Department of Dermatology, General Hospital of People' s Liberation Army, Beijing 100853 (China)

    2016-05-13

    MAGE-A1 belongs to the chromosome X-clustered genes of cancer-testis antigen family and is normally expressed in the human germ line but is also overexpressed in various tumors. Previous studies of MAGE-A1 in melanoma mainly focused on methylation changes or its role in immunotherapy, however, its biological functions in melanoma have remained unknown. In order to determine the role of MAGE-A1 in melanoma growth and metastasis, we manipulated melanoma cell lines with overexpression and knockdown of MAGE-A1. Integration of cell proliferation assays, transwell migration and invasion assays, and RNA-Seq analysis revealed that up-regulation of MAGE-A1 dramatically promoted proliferation, migration, and invasion of human melanoma cell lines in vitro, while down-regulation of MAGE-A1 inhibited those characteristics associated with tumor cells. Furthermore, transcriptome sequencing revealed that MAGE-A1 exerts its tumor promoting activity by activating p-C-JUN directly or through ERK-MAPK signaling pathways. Based on our findings, we propose that MAGE-A1 may be a potential therapeutic target for melanoma patients. - Highlights: • MAGE-A1 promotes proliferation and clone formation in melanoma cell lines. • MAGE-A1 enhances tumor cell migration and invasion in melanoma cell lines. • Network including C-JUN, IL8, and ARHGAP29 play critical role in malignant melanoma. • Oncogenic MAGE-A1 increases p-C-JUN levels, possibly via ERK-MAPK signaling pathway.

  8. The MLK family mediates c-Jun N-terminal kinase activation in neuronal apoptosis.

    Science.gov (United States)

    Xu, Z; Maroney, A C; Dobrzanski, P; Kukekov, N V; Greene, L A

    2001-07-01

    Neuronal apoptotic death induced by nerve growth factor (NGF) deprivation is reported to be in part mediated through a pathway that includes Rac1 and Cdc42, mitogen-activated protein kinase kinases 4 and 7 (MKK4 and -7), c-Jun N-terminal kinases (JNKs), and c-Jun. However, additional components of the pathway remain to be defined. We show here that members of the mixed-lineage kinase (MLK) family (including MLK1, MLK2, MLK3, and dual leucine zipper kinase [DLK]) are expressed in neuronal cells and are likely to act between Rac1/Cdc42 and MKK4 and -7 in death signaling. Overexpression of MLKs effectively induces apoptotic death of cultured neuronal PC12 cells and sympathetic neurons, while expression of dominant-negative forms of MLKs suppresses death evoked by NGF deprivation or expression of activated forms of Rac1 and Cdc42. CEP-1347 (KT7515), which blocks neuronal death caused by NGF deprivation and a variety of additional apoptotic stimuli and which selectively inhibits the activities of MLKs, effectively protects neuronal PC12 cells from death induced by overexpression of MLK family members. In addition, NGF deprivation or UV irradiation leads to an increase in both level and phosphorylation of endogenous DLK. These observations support a role for MLKs in the neuronal death mechanism. With respect to ordering the death pathway, dominant-negative forms of MKK4 and -7 and c-Jun are protective against death induced by MLK overexpression, placing MLKs upstream of these kinases. Additional findings place the MLKs upstream of mitochondrial cytochrome c release and caspase activation.

  9. Activation of c-Jun N-terminal Kinases by Ribotoxic Stresses

    Institute of Scientific and Technical Information of China (English)

    Dong-Yun Ouyang; Yuan-Yuan Wang; Yong-Tang Zheng

    2005-01-01

    The c-Jun N-terminal kinases (JNKs) are classic stress-activated protein kinases. Many cellular stresses have been shown to stimulate JNK activation. In this review, we focus on ribotoxic stresses based on their multiple biological potencies including anti-HIV-1 activity. Some of the functions of ribotoxins and the signaling transduction pathway that mediated are mentioned. Different from other stimulators, ribotoxic stresses act on special motifs of 28S rRNA in translationally active mammal ribosomes. Binding and damaging on the motif leads to JNK activation and subsequently biological response to the signal initiator, which is named ribotoxic stress response.

  10. Discussion of vicarious calibration of GOSAT/TANSO-CAI UV-band (380nm) and aerosol retrieval in wildfire region in the OCO-2 and GOSAT observation campaign at Railroad Valley in 2016

    Science.gov (United States)

    Hashimoto, M.; Kuze, A.; Bruegge, C. J.; Shiomi, K.; Kataoka, F.; Kikuchi, N.; Arai, T.; Kasai, K.; Nakajima, T.

    2016-12-01

    The GOSAT (Greenhouse Gases Observing Satellite) / TANSO-CAI (Cloud and Aerosol Imager, CAI) is an imaging sensor to measure cloud and aerosol properties and observes reflected sunlight from the atmosphere and surface of the ground. The sensor has four bands from near ultraviolet (near-UV) to shortwave infrared, 380, 674, 870 and 1600nm. The field of view size is 0.5 km for band-1 through band-3, and 1.5km for band-4. Band-1 (380nm) is one of unique function of the CAI. The near-UV observation offers several advantages for the remote sensing of aerosols over land: Low reflectance of most surfaces; Sensitivity to absorbing aerosols; Absorption of trace gases is weak (Höller et al., 2004). CAI UV-band is useful to distinguish absorbing aerosol (smoke) from cloud. GOSAT-2/TANSO-CAI-2 that will be launched in the future also has UV-bands, 340 and 380nm. We carried out an experiment to calibrate CAI UV-band radiance using data taken in a field campaign of OCO-2 and GOSAT at Railroad Valley in 2016. The campaign period is June 27 to July 3 in 2016. We measured surface reflectance by using USB4000 Spectrometer with 74-UV collimating lens (Ocean Optics) and Spectralon (Labsphere). USB4000 is a UV spectrometer, and its measurement range from 300 to 520nm. We simulated CAI UV-band radiance using a vector type of radiation transfer code, i.e. including polarization calculation, pstar3 (Ota et al., 2010) using measured surface reflectance and atmospheric data, pressure and relative humidity by radiosonde in the same campaign, and aerosol optical depth by AERONET, etc. Then, we evaluated measured UV radiances with the simulated data. We show the result of vicarious calibration of CAI UV-band in the campaign, and discuss about this method for future sensor, CAI-2. Around the campaign period, there was wildfire around Los Angeles, and aerosol optical thickness (AOT) observed by AERONET at Rail Road valley and Caltech sites is also high. We tried to detect and retrieve aerosol

  11. Expression of c-jun in brain stem following moderate lateral fluid percussion brain injury in rats

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    AIM: To study the expression of c-jun in brain stem following moderate lateral fluid percussion brain injury in rats, and to observe the temporal patterns of its expressions following percussion.METHODS: Male Sprague-Dawley rats were divided into normal control, sham operation control and injury groups. The rats of injury group subjected to moderate lateral fluid percussion injury (0.2 mPa), and then were subdivided into 5 min, 15 min, 30 min, 1 h, 2 h, 4 h, 8 h and 12 h groups according to the time elapsed after injury. The expression of c-jun was studied by immunohistochemistry and in situ hybridization. RESULTS: After percussion for 15 min, Jun positive neurons increased in brain stem progressively, and peaked at 12h. At 5min after percussion, the induction of c-jun mRNA was increased, and remained elevated up to 1h-2h after brain injury. CONCLUSION: The induction and expression of the c-jun in brain stem after fluid percussion brain injury were increased rapidly and lasted for a long time.

  12. JNK/c-Jun signaling pathway mediates the fluoride-induced down-regulation of MMP-20 in vitro

    Science.gov (United States)

    Zhang, Yan; Li, Wu; Chi, Hae Sun; Chen, James; DenBesten, Pamela K.

    2008-01-01

    Delayed removal of amelogenins, which are initially hydrolyzed by matrix metalloproteinase MMP-20, is a characteristic of enamel fluorosis. In this study, we investigated the regulation of MMP-20 and possible effects of fluoride on MMP-20 expression in human ameloblast lineage cells. Protein expression and signaling pathways of human ameloblast lineage cells, exposed to 10 μM fluoride, were compared to control cells without fluoride exposure. The role of activator protein-1 in MMP-20 regulation was analyzed by DNA-protein affinity precipitation and luciferase reporter gene assays. MMP-20 protein levels in human ameloblast lineage cells decreased in the presence of fluoride, while amelogenin and TIMP-2 were not altered. Fluoride also decreased the transcription of a luciferase reporter gene driven by the MMP-20 promoter. Down-regulation of MMP-20 by fluoride was related to suppression of JNK/c-Jun phosphorylation. In contrast, the JNK activator elevated the expression of MMP-20. Three c-Jun binding sites on the MMP-20 promoter were identified for the first time, and were occupied by c-Jun as MMP-20 was induced. Deletion of any one of AP-1 binding sites on the MMP-20 promoter significantly reduced the transcription of downstream luciferase reporter. These in vitro findings suggest that c-Jun is a key regulatory element for MMP-20 expression, and human ameloblast lineage cells can respond to fluoride by down-regulating MMP-20 transcription through the JNK/c-Jun signaling pathway. PMID:17611094

  13. A New Type of Foreign Clast in A Polymict Ureilite: A CAI or AL-Rich Chondrule

    Science.gov (United States)

    Goodrich, C. A.; Ross, D. K.; Treiman, A. H.

    2017-01-01

    Introduction: Polymict ureilites are breccias interpreted to represent regolith formed on a ureilitic asteroid [1-3]. They consist of approximately 90-95% clasts of various ureilite types (olivine-pyroxene rocks with Fo 75-95), a few % indigenous feldspathic clasts, and a few % foreign clasts [4-20]. The foreign clasts are diverse, including fragments of H, L, LL and R chondrites, angrites, other achondrites, and dark clasts similar to CC [6,7,9-19]. We report a new type of foreign clast in polymict ureilite DaG 999. Methods: Clast 8 in Dar al Gani (DaG) 999/1 (Museum fur Naturkunde) was discovered during a survey of feldspathic clasts in polymict ureilites [19,20]. It was studied by BEI, EMPA, and X-ray mapping on the JEOL 8530F electron microprobe at ARES, JSC. Petrography and Mineral Compositions: Clast 8 is sub-rounded to irregular in shape, approximately 85 micrometers in diameter, and consists of approximately 68% pyroxene and 32% mesostasis (by area). Part of the pyroxene (top half of clast in Fig. 1a and 2) shows a coarse dendritic morphology; the rest appears massive. Mesostasis may be glassy and contains fine needles/grains of pyroxene. The pyroxene has very high CaO (23.5 wt.%) and Al2O3 (19.7 wt.%), with the formula: (Ca(0.91)Mg(0.63)Fe(0.01)Al(sup VI) (0.38)Cr(0.01)Ti(0.05)1.99 Si2O6. The bulk mesostasis also has very high Al2O3 (approximately 26 wt.%). A bulk composition for the clast was obtained by combining modal abundances with phase compositions (Table 1, Fig. 3). Discussion: The pyroxene in clast 8 has a Ca-Al-(Ti)- rich (fassaitic) composition that is clearly distinct from compositions of pyroxenes in main group ureilites [22] or indigenous feldspathic clasts in polymict ureilites [4-8]. It also has significantly higher Al than fassaite in angrites (up to approximately 12 wt.% [23]), which occur as xenoliths in polymict ureilites. Ca-Al-Ti rich pyroxenes are most commonly found in CAIs, Al-rich chondrules and other types of refractory

  14. A new role for the Kruppel-like transcription factor KLF6 as an inhibitor of c-Jun proto-oncoprotein function.

    Science.gov (United States)

    Slavin, Daniela A; Koritschoner, Nicolás P; Prieto, Claudio C; López-Díaz, Fernando J; Chatton, Bruno; Bocco, José Luis

    2004-10-28

    Kruppel-like transcription factors (KLFs) represent one of the most diverse set of regulators in vertebrate organisms. KLF family members are involved in cell proliferation and differentiation control in normal as well as in pathological situations. Here, we demonstrate that KLF6 behaves as a functional antagonist of the c-Jun proto-oncoprotein. Thus, KLF6 overexpression downregulated c-Jun-dependent transcription and a physical interaction between c-Jun and KLF6 was detected. Moreover, cell proliferation induced by c-Jun was significantly decreased by KLF6. The inhibition of c-Jun functions correlates directly with c-Jun protein degradation induced by KLF6. We also show that all KLF6 effects on c-Jun were largely dependent on phorbol ester (TPA/ionomycin) extracellular stimulation, which enhanced KLF6 nuclear translocation and transcriptional activity and modified its phosphorylation status. Our data are consistent with a novel mechanism of KLF6's role as an inhibitor of cell proliferation by counteracting the function of the c-Jun proto-oncoprotein involving enhanced c-Jun degradation by the proteasome-dependent pathway, and further reinforces KLF6 as a potential tumor suppressor gene product.

  15. Role for c-jun N-terminal kinase in treatment-refractory acute myeloid leukemia (AML): signaling to multidrug-efflux and hyperproliferation.

    Science.gov (United States)

    Cripe, L D; Gelfanov, V M; Smith, E A; Spigel, D R; Phillips, C A; Gabig, T G; Jung, S-H; Fyffe, J; Hartman, A D; Kneebone, P; Mercola, D; Burgess, G S; Boswell, H S

    2002-05-01

    A relationship was proved between constitutive activity of leukemic cell c-jun-N-terminal kinase (JNK) and treatment failure in AML. Specifically, early treatment failure was predicted by the presence of constitutive JNK activity. The mechanistic origins of this association was sought. A multidrug resistant leukemic cell line, HL-60/ADR, characterized by hyperexpression of c-jun and JNK activity, was transfected with a mutant c-jun vector, whose substrate N-terminal c-jun serines were mutated. Down-regulated expression occurred of c-jun/AP-1-dependent genes, catalase and glutathione-S-transferase (GST) pi, which participate in cellular homeostasis to oxidative stress and xenobiotic exposure. MRP-efflux was abrogated in HL-60/ADR cells with dominant-negative c-jun, perhaps because MRP1 protein expression was also lost. Heightened sensitivity to daunorubicin resulted in cells subjected to this change. Biochemical analysis in 67 primary adult AML samples established a statistical correlation between cellular expression of c-jun and JNK activity, JNK activity with hyperleukocytosis at presentation of disease, and with exuberant MRP efflux. These findings reflect the survival role for c-jun/AP-1 and its regulatory kinase previously demonstrated for yeast in homeostatic response to oxidative stress and in operation of ATP-binding cassette efflux pumps, and may support evolutionary conservation of such function. Thus, JNK and c-jun may be salient drug targets in multidrug resistant AML.

  16. Correlation between spina bifida manifesta in fetal rats and c-Jun N-terminal kinase signaling

    Institute of Scientific and Technical Information of China (English)

    Yinghuan Ma; Yongxin Bao; Chenghao Li; Fubin Jiao; Hongjie Xin; Zhengwei Yuan

    2012-01-01

    Fetal rat models with neural tube defects were established by injection with retinoic acid at 10 days after conception. The immunofluorescence assay and western blot analysis showed that the number of caspase-3 positive cells in myeloid tissues for spina bifida manifesta was increased. There was also increased phosphorylation of c-Jun N-terminal kinase, a member of the mitogen activated protein kinase family. The c-Jun N-terminal kinase phosphorylation level was positively correlated with caspase-3 expression in myeloid tissues for spina bifida manifesta. Experimental findings indicate that abnormal apoptosis is involved in retinoic acid-induced dominant spina bifida formation in fetal rats, and may be associated with the c-Jun N-terminal kinase signal transduction pathway.

  17. Correlation between spina bifida manifesta in fetal rats and c-Jun N-terminal kinase signaling★

    Science.gov (United States)

    Ma, Yinghuan; Bao, Yongxin; Li, Chenghao; Jiao, Fubin; Xin, Hongjie; Yuan, Zhengwei

    2012-01-01

    Fetal rat models with neural tube defects were established by injection with retinoic acid at 10 days after conception. The immunofluorescence assay and western blot analysis showed that the number of caspase-3 positive cells in myeloid tissues for spina bifida manifesta was increased. There was also increased phosphorylation of c-Jun N-terminal kinase, a member of the mitogen activated protein kinase family. The c-Jun N-terminal kinase phosphorylation level was positively correlated with caspase-3 expression in myeloid tissues for spina bifida manifesta. Experimental findings indicate that abnormal apoptosis is involved in retinoic acid-induced dominant spina bifida formation in fetal rats, and may be associated with the c-Jun N-terminal kinase signal transduction pathway. PMID:25337099

  18. Expression of c-fos and c-jun protooncogenes in the uteri of immature mice neonatally exposed to diethylstilbestrol.

    Science.gov (United States)

    Yamashita, S; Takayanagi, A; Shimizu, N

    2003-01-01

    We studied the cell-type-specific and temporal expression of c-fos and c-jun protooncogenes after 17beta-estradiol (E2) stimulation in the uteri of immature 3-week-old mice neonatally exposed to diethylstilbestrol (DES), DES-mice, and the ontogenic expression of these genes in the uteri of DES-mice using immunohistochemistry and in situ hybridization. A single E2 injection induced the transient and rapid expression of c-fos mRNA and c-Fos protein in the endometrial epithelium and endothelial cells of the blood vessels in both 3-week-old vehicle-treated controls and DES-mice; a peak of mRNA expression was 2 hours after E2 injection and that of protein expression was 2 to 3 hours after the injection. The expression of c-fos mRNA and protein after E2 stimulation was lower in the DES-mice than in the control animals. There were no significant differences in the c-jun expression patterns in both experimental groups before and after the E2 injection. The E2 injection transiently down-regulated the c-jun expression in the epithelium and up-regulated it in the stroma and myometrium. The uterine epithelium of DES-mice showed much stronger c-Jun immunostaining on days 4 and 10, compared with those of controls. Neonatal DES treatment reduced c-Jun immunoreactivity in the uterine epithelium on days 4 and 10, and increased the reaction in the stroma on day 4. These results suggested that the neonatal DES treatment induces permanent changes in the c-fos expression pattern independent of the postpuberal secretion of ovarian steroids. The changes in the expression of c-fos and c-jun protooncogenes, particularly during postnatal development, are likely to play important roles in the production of uterine abnormalities in the DES-mice.

  19. From reptilian phylogenomics to reptilian genomes: analyses of c-Jun and DJ-1 proto-oncogenes.

    Science.gov (United States)

    Katsu, Y; Braun, E L; Guillette, L J; Iguchi, T

    2009-01-01

    Genome projects have revolutionized our understanding of both molecular biology and evolution, but there has been a limited collection of genomic data from reptiles. This is surprising given the pivotal position of reptiles in vertebrate phylogeny and the potential utility of information from reptiles for understanding a number of biological phenomena, such as sex determination. Although there are many potential uses for genomic data, one important and useful approach is phylogenomics. Here we report cDNA sequences for the c-Jun(JUN) and DJ-1(PARK7) proto-oncogenes from 3 reptiles (the American alligator, Nile crocodile, and Florida red-belly turtle), show that both genes are expressed in the alligator, and integrate them into analyses of their homologs from other organisms. With these taxa it was possible to conduct analyses that include all major vertebrate lineages. Analyses of c-Jun revealed an unexpected but well-supported frog-turtle clade while analyses of DJ-1 revealed a topology largely congruent with expectation based upon other data. The conflict between the c-Jun topology and expectation appears to reflect the overlap between c-Jun and a CpG island in most taxa, including crocodilians. This CpG island is absent in the frog and turtle, and convergence in base composition appears to be at least partially responsible for the signal uniting these taxa. Noise reduction approaches can eliminate the unexpected frog-turtle clade, demonstrating that multiple signals are present in the c-Jun alignment. We used phylogenetic methods to visualize these signals; we suggest that examining both historical and non-historical signals will prove important for phylogenomic analyses.

  20. A Revision on Brief Biography for a Writer Named CAI Tao in Xianyou%仙游籍文学家蔡僚小传辑补

    Institute of Scientific and Technical Information of China (English)

    李亮亮

    2012-01-01

    The History of Song Dynasty did not have a biography for CAI Tao who was one of writers in Xianyou acrossing Northem Song Dynasty and Southern Song Dynasty, while Songshi Yi gave a simple introduction about him. Other biographies for him some left gaps while some gave the wrong imformation. At present, there's not systematic research on CAI Tao's biography in academic circles. Therefore, this article makes a reversion on it.%两宋之交仙游籍文学家蔡僚,《宋史》无传;《宋史翼》其本传尚嫌简略。其他小传或有缺漏,或有讹误。目前学界对于其生平缺乏系统考证,特予考辨、辑补。

  1. 体育院校篮球裁判CAI课件的研制%Development of sports college basketball referee CAI courseware

    Institute of Scientific and Technical Information of China (English)

    阮长庆

    2014-01-01

    随着社会经济的不断发展进步,多媒体、网络等技术也得到了迅速普及。在体育院校篮球裁判教学中中应用CAI课件也成为潮流趋势。CAI课件作为一种辅助教学手段,集图像、动画、声音以及文本为一体。%With the development of society economy, multimedia,network technology has been the rapid popularization.Application of CAI courseware in the basketball referee teaching in the sports colleges and universities has become a trend. CAI courseware as an auxiliary means of teaching,image,animation,sound and text as a whole.

  2. Investigation of combustion, performance and emission characteristics of 2-stroke and 4-stroke spark ignition and CAI/HCCI operations in a DI gasoline

    OpenAIRE

    Y. Zhang; Zhao, H.

    2014-01-01

    In order to develop more efficient and cleaner gasoline engines, a number of new engine operating strategies have been proposed and researched on different engines, including the spark ignition (SI) and controlled autoignition (CAI) or HCCI in both 2-stroke and 4-stroke cycles in a poppet valve engine. In this work, a single cylinder direct injection gasoline engine equipped with an electro-hydraulic valve-train system has been commissioned and used to achieve seven different operating modes,...

  3. How CAI Correctly Play a Role in Teaching%如何在教学中正确发挥CAI的作用

    Institute of Scientific and Technical Information of China (English)

    苏醒

    2011-01-01

    CAI (Computer-assisted Instruction) refers to transmit the information in teaching using computer and computer technology to complete the task of teaching and achieve educational purposes. CAI can integrate animation, sound, text etc. together, which not only be help to teaching, but also help students form new ideas, new concepts and new methods in the learning process, and is a powerful tool and form of developing student potential and developing their intelligence and ability. However, in actual use there were many problems. The foUowing is my view about the role of CAI in the classroom teaching, according to my personal experience in teaching.%CAI(计算机辅助教学)是指在教学活动中,利用计算机及其技术传导教学过程中的信息,完成教学任务,达到教学目的.利用CAI能使动画、声音,文字等地切入融为一体的特点,不仅有利于教学,更有利于学生在学习过程中形成新思想、新观念和新方法,是开发学生潜能,发展学生智力和能力的有力工具和形式.但是在实际使用过程中又出现了许多的问题,以下是我根据个人教学经验谈谈CAI在课堂教学中应用到底发挥多大作用.

  4. 蔡淦辨治慢性萎缩性胃炎经验%Cai Gan's Experience in Differentiating and Treating Chronic Atrophic Gastritis

    Institute of Scientific and Technical Information of China (English)

    刘晓谷; 蔡淦

    2009-01-01

    This article presents Professor Cai Can's experience in the differentiation and treatment of chronic atrophic gastritis(CAG). He emphasizes holism, dynamic and balance and three proven cases were introduced.%介绍蔡淦教授治疗慢性萎缩性胃炎的经验,辨证论治强调整体观、动态观、平衡观.并举验案3则.

  5. Zhang Jun and Luo Theory%张浚与洛学

    Institute of Scientific and Technical Information of China (English)

    金生杨

    2011-01-01

    Zhang Jun, a minister during the reign of Emperor Gaozong and Emperor Xiaozong in the Southern Song Dynasty, played an important role in academic evolvement of the Song Dynasty. On the one hand, he appreciated Luo theory and recommended its scholars, creating an 'early Yuanyou political situation' and rejuvenating Luo theory, when he was appointed prime minister with Zhao Ding in the early Southern Song Dynasty. On the other hand, he advocated the theory of filial duty while restraining the development of Yuanyou's theory, when he became the only prime minister. He believed then that neither Yuanyou's theory was absolutely right, nor Xifeng's theory was completely wrong. But after Qing Hui dominated the court, Zhang Jun was banished. In exile, he accepted Luo theory completely and continued to advocate it by writing books and instructing his son Zhang Shi in learning the theory. Because of that, Zhang Jun was appointed minister in the period of Emperor Xiaozong and left a good name to posterity.%张浚在南宋高、孝两朝出将入相,对宋代学术起着重要作用。他在南宋初与赵鼎并相,推崇洛学,引擢洛学之士,造就“小元祜”政局,为洛学的复兴吹响了号角;另一方面,他又主张元祜未必全是、熙丰未必全非,倡行孝悌之说,打压洛学,使洛学的发展受到抑制。秦桧专政后,张浚被贬斥,在困顿谪居期间,张浚终信洛学,著书立说,继承弘扬洛学,并引导其子张轼追随洛学。张浚对洛学的推崇使他在孝宗朝再受重用,流誉于后世,甚至掩盖其过失。

  6. Histological structure and distribution of carbonic anhydrase isozymes (CA-I, II, III and VI) in major salivary glands in koalas.

    Science.gov (United States)

    Mizuno, T; McKinnon, A; Ichihara, N; Amasaki, T; Asari, M; Nishita, T; Oishi, M; Soeta, S; Amasaki, H

    2009-11-01

    While the mandibular glands usually consist of only mucous acinar cells or a combination of mucous and serous cells in other species of mammals, those of koalas were serous glands. Rabbit mono-specific polyclonal anti-canine CA-I, II, III or VI antiserum showed cross-reactivity against corresponding koala carbonic anhydrase (CA) isozymes. Although immunohistochemical reactions to CA-I, II and VI in ductal cells were moderate to strong in the tested salivary glands, no reaction or only slight reactions were observed against CA-III. In the sublingual glands, moderate immunohistochemical reactions to CA-I, II and VI were also evident in serous acinar cells and serous demilunes. However, no reactions to the tested isozymes were observed in mucous acinar cells in these glands. With the exception of the histological structure of the mandibular glands, histological features and the distributional profile of CA isozymes of the salivary glands in koalas are relatively close to results obtained from horses.

  7. Procedimiento para medir y valorar la eficiencia empresarial en el CAI Arrocero Sur del Jíbaro.

    Directory of Open Access Journals (Sweden)

    Boris Luis Rodríguez Rodríguez

    2007-06-01

    Full Text Available En la presente investigación titulada Procedimiento para medir y valorar la eficiencia empresarial en el CAI Arrocero “Sur del Jíbaro” se realiza un amplio análisis de la bibliografía, basado en dos variables fundamentales, procedimientos específicos y eficiencia empresarial definiendo como objetivo la necesidad que existe de desarrollar un procedimiento específico para medir y valorar la eficiencia. Es por ello que se propone un procedimiento específico, a través de la siguiente secuencia de pasos lógicos: Identificación de los indicadores de eficiencia, importancia de los indicadores según expertos, comportamiento de los indicadores en la organización, determinación del indicador general de eficiencia, valoración integral de la eficiencia en la organización. Resulta de gran utilidad práctica para la empresa el cálculo del IGE pues permite desde el punto de vista cuantitativo brindar una información de cómo está la empresa partiendo de la importancia relativa de cada uno de los indicadores y el comportamiento de ellos en el marco de la empresa, comprobando que el indicador general de eficiencia no se comporta de manera uniforme en todas las Unidades Empresariales de Base (UEB.

  8. Dieta de Leopardus colocolo (Carnivora: Felidae en la Reserva Nacional de Junín, Junín, Perú

    Directory of Open Access Journals (Sweden)

    Ursula Fajardo

    2014-05-01

    Full Text Available Este estudio caracteriza la dieta de Leopardus colocolo en los alrededores del lago Junín, en el centro del Perú, a partir de los restos de las presas presentes en 43 heces. El origen de las heces del predador se determinó a partir del ADN mitocondrial de las células epiteliales intestinales adheridas a la superficie de las heces, utilizando como marcador la región de control. Los restos de las presas fueron identificados utilizando literatura especializada y la comparación con especímenes de colección, identificando un total of 14 ítems alimenticios pertenecientes a mamíferos de las familias Cricetidae (6, Chinchillidae (1 y Caviidae (1 y aves de las familias Anatidae (3 y Rallidae (2, y un grupo de aves no identificadas (1. Los roedores fueron el principal componente de la dieta de L. colocolo, en frecuencia y biomasa, seguido por las aves. Entre los ítems alimenticios consumidos, el roedor cricétido pequeño Calomys sp. fue el más frecuente; sin embargo, el mayor aporte de biomasa relativa fue proporcionado por el roedor mediano Cavia tschudii. La amplitud de nicho obtenida fue baja (Bsta= 0.17, indicando una dieta especializada. Nuestros resultados confirman que, como ocurre con la mayoría de felinos pequeños neotropicales, L. colocolo es un predador especializado en la captura de vertebrados, principalmente mamíferos pequeños. No se registró variación estacional en la dieta y el análisis de las clases de edad de los roedores cricétidos mostró que los adultos fueron los más consumidos. Se infiere que L. colocolo tiene un patrón de actividad diurno y nocturno.

  9. Growth hormone induces expression of c-jun and jun B oncogenes and employs a protein kinase C signal transduction pathway for the induction of c-fos oncogene expression.

    Science.gov (United States)

    Slootweg, M C; de Groot, R P; Herrmann-Erlee, M P; Koornneef, I; Kruijer, W; Kramer, Y M

    1991-04-01

    Although the structure of several members of the GH receptor family has been defined, signal transduction following GH binding to its receptor has not been elucidated. Mouse osteoblasts were used to study the effect of GH on immediate early gene expression and, subsequently, the cellular signal(s) mediating this expression were analysed. GH rapidly and transiently induced the expression of c-jun and jun B in concert with the already reported expression of c-fos. The GH-induced expression of c-fos was completely blocked by the protein kinase inhibitors staurosporine and H7, indicating that the action of GH is mediated by one or several protein kinases. We next analysed the identity of the putative protein kinases in more detail by using a more specific protein kinase inhibitor, namely the ether-lipid 1-O-alkyl-2-O-methylglycerol, understood to be an inhibitor of protein kinase C (PKC). Data obtained from these studies revealed that GH-induced expression of c-fos is mediated by PKC. In addition, we observed a profound increase in formation of the PKC activator diacyglycerol upon addition of GH, a natural activator of PKC. In conclusion, upon binding of GH to mouse osteoblasts, the receptor-mediated cellular signal involves diacyglycerol formation and activation of PKC, leading to the induction of oncogene expression. Finally, the expression of c-fos, c-jun and jun B results in an increased binding of protein complexes to AP-1 binding sites.

  10. Expression and Purification of Z Protein from Junín Virus

    Directory of Open Access Journals (Sweden)

    S. E. Goñi

    2010-01-01

    Full Text Available Arenaviridae comprises 23 recognized virus species with a bipartite ssRNA genome and an ambisense coding strategy. The virions are enveloped and include nonequimolar amounts of each genomic RNA species, designated L and S, coding for four ORFs (N, GPC, L, and Z. The arenavirus Junín (JUNV is the etiological agent of Argentine Hemorrhagic Fever, an acute disease with high mortality rate. It has been proposed that Z is the functional counterpart of the matrix proteins found in other negative-stranded enveloped RNA viruses. Here we report the optimized expression of a synthetic gene of Z protein, using three expression systems (two bacterial and a baculoviral one. One of these recombinant proteins was used to generate antibodies. A bioinformatic analysis was made where Z was subdivided into three domains. The data presented contributes methodologies for Z recombinant production and provides the basis for the development of new experiments to test its function.

  11. Immediate-early Inducible Function in Upstream Region of junB Gene

    Institute of Scientific and Technical Information of China (English)

    HONG WAN; HIROSHI ISHIHARA; IZUMI TANAKA

    2006-01-01

    Objective To analyze the upstream region of radiation-induced junB gene. Methods Four plasmids containing 250 bp, 590 bp, 900 bp and 1650 bp, and CAT reporter gene were constructed separately and introduced to L8704 cells. The cells were irradiated with 2 Gy X-rays and incubated at different intervals. Total RNA was extracted from the cells and fluctuation of the CAT mRNA level was assessed by the RNA ratio of CAT/β-actin measured by quantitative Northern blot hybridization. Results CAT mRNA expression containing 900 bp and 1560 bpjunB promoter remarkably and rapidly increased, and reached its peak 30 min after 2 Gy X-ray irradiation. Conclusions 590~900 bp fragments located in the upstream region ofjunB gene play an important role in the early process of cells against radiation.

  12. Endothelial Cell Permeability and Adherens Junction Disruption Induced by Junín Virus Infection

    Science.gov (United States)

    Lander, Heather M.; Grant, Ashley M.; Albrecht, Thomas; Hill, Terence; Peters, Clarence J.

    2014-01-01

    Junín virus (JUNV) is endemic to the fertile Pampas of Argentina, maintained in nature by the rodent host Calomys musculinus, and the causative agent of Argentine hemorrhagic fever (AHF), which is characterized by vascular dysfunction and fluid distribution abnormalities. Clinical as well as experimental studies implicate involvement of the endothelium in the pathogenesis of AHF, although little is known of its role. JUNV has been shown to result in productive infection of endothelial cells (ECs) in vitro with no visible cytopathic effects. In this study, we show that direct JUNV infection of primary human ECs results in increased vascular permeability as measured by electric cell substrate impedance sensing and transwell permeability assays. We also show that EC adherens junctions are disrupted during virus infection, which may provide insight into the role of the endothelium in the pathogenesis of AHF and possibly, other viral hemorrhagic fevers. PMID:24710609

  13. Inhibitors of c-Jun phosphorylation impede ovine primordial follicle activation.

    Science.gov (United States)

    Bertoldo, Michael J; Bernard, Jérémy; Duffard, Nicolas; Tsikis, Guillaume; Alves, Sabine; Calais, Laure; Uzbekova, Svetlana; Monniaux, Danielle; Mermillod, Pascal; Locatelli, Yann

    2016-05-01

    Is the c-Jun-N-terminal kinase (JNK) pathway implicated in primordial follicle activation? Culture of ovine ovarian cortex in the presence of two different c-Jun phosphorylation inhibitors impeded pre-antral follicle activation. Despite its importance for fertility preservation therapies, the mechanisms of primordial follicle activation are poorly understood. Amongst different signalling pathways potentially involved, the JNK pathway has been previously shown to be essential for cell cycle progression and pre-antral follicle development in mice. Ovine ovarian cortex pieces were cultured with varying concentrations of SP600125, JNK inhibitor VIII or anti-Mullerian hormone (AMH) in the presence of FSH for 9 days. Follicular morphometry and immunohistochemistry for proliferating cell nuclear antigen (PCNA), apoptosis and follicle activation (Foxo3a) were assessed. Inhibition of primordial follicle activation occurred in the presence of SP600125, JNK inhibitor VIII and AMH when compared with controls (all P primordial follicle development, we did not determine the cellular targets and mechanism of action of the inhibitors. These results are the first to implicate the JNK pathway in primordial follicle activation and could have significant consequences for the successful development of fertility preservation strategies and our understanding of primordial follicle activation. n/a. Dr Michael J. Bertoldo and the laboratories involved in the present study were supported by a grant from 'Région Centre' (CRYOVAIRE, Grant number #320000268). There are no conflicts of interest to declare. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  14. Calcium has a permissive role in interleukin-1beta-induced c-jun N-terminal kinase activation in insulin-secreting cells

    DEFF Research Database (Denmark)

    Størling, Joachim; Zaitsev, Sergei V; Kapelioukh, Iouri L

    2005-01-01

    phosphorylation of the JNK substrate c-jun and reduced IL-1beta-stimulated activation of JNK1/2 as assessed by immunoblotting. Inhibition of IL-1beta-induced in vitro kinase activity toward c-jun after collective L- and T-type Ca(2+) channel blockade was confirmed in primary rat and ob/ob mouse islets...

  15. 从教育学习理论看CAI课件写作%CAI courseware writing from the education and learning theory

    Institute of Scientific and Technical Information of China (English)

    杨旭超

    2015-01-01

    Behaviorism, cognitivism, and constructivism have led the CAI courseware writing. Situated cognition and learning theory, whose meaning of knowledge can't be derived without specific situation, inherit and develop the leading model of other educational learning theory to CAI courseware writing. Authenticity is the premise of creative situation, which should accord with the objective rule of real life and objects. Situational teaching, which varies from different person, time, and place, should be designed as the most important goal for CAI courseware writing. In addition, creative situation should unify knowledge, science, ideology and interest. Through learning theory guiding CAI courseware writing, CAI courseware has become more accorded with the laws of education to serve the teaching and learning activities better.%行为主义、认知主义、建构主义都曾经指导了CAI课件写作。情境认知与学习理论继承并发展了其他教育学习理论对CAI课件写作的指导,认为:CAI课件中知识的意义不能脱离具体的情境产生。真实性是创设情境的前提,情境创设应符合现实生活场景和事物运动的客观规律,情境性教学应作为CAI课件写作的最重要目标进行设计,要因人、因时、因地而异。此外,情境创设还必须保持情境的知识性、科学性、思想性和趣味性的统一。通过教育学习理论指导CAI课件写作,使CAI课件更符合教育规律,能够更好地服务于教学活动和学习活动。

  16. Palbociclib inhibits epithelial-mesenchymal transition and metastasis in breast cancer via c-Jun/COX-2 signaling pathway.

    Science.gov (United States)

    Qin, Ge; Xu, Fei; Qin, Tao; Zheng, Qiufan; Shi, Dingbo; Xia, Wen; Tian, Yun; Tang, Yanlai; Wang, Jingshu; Xiao, Xiangshen; Deng, Wuguo; Wang, Shusen

    2015-12-08

    Palbociclib, a highly selective CDK4/6 inhibitor, has been shown to be a novel anti-tumor agent that suppresses breast cancer cell proliferation. However, its anti-metastasis activity remains controversial. In the present study, we evaluated whether palbociclib prevented breast cancer cell metastasis and revealed its regulatory mechanism. We found that palbociclib inhibited migration and invasion in the breast cancer cells MDA-MB-231 and T47D. The epithelial-mesenchymal transition (EMT) markers, vimentin and Snail, were down-regulated with palbociclib treatment. Moreover, we revealed that this inhibition was mediated by the c-Jun/COX-2 pathway. COX-2 was decreased after palbociclib treatment. The production of PGE2 was also reduced along with COX-2. Additionally, our data showed that c-Jun, a crucial transcriptional regulator of COX-2, was down-regulated by palbociclib. We found that palbociclib weakened the COX-2 promoter binding activity of c-Jun and prevented its translocation from the cytoplasm to cell nuclei. Bioluminescence imaging and tail intravenous injection were used to evaluate the anti-metastasis effect of palbociclib in vivo. The data demonstrated that palbociclib reduced breast cancer metastasis to the lung. These results therefore demonstrated that the anti-metastasis activity of palbociclib is mediated via the c-Jun/COX-2 signaling pathway by inhibiting EMT in breast cancer cells.

  17. Dentin bonding agents induce c-fos and c-jun protooncogenes expression in human gingival fibroblasts.

    Science.gov (United States)

    Huang, Fu-Mei; Chou, Ming-Yung; Chang, Yu-Chao

    2003-01-01

    An important requirement for a dentin bonding agent is biologic compatibility; the bonding agent usually remains in close contact with living dental tissues over a long period of time. Information on the genotoxicity/mutagenicity and cacinogenicity potentials of dentin bonding agents is rare. It has been shown that c-fos and c-jun are induced rapidly by a variety of chemical and physical stimuli. Little is known about the induction of cellular signaling events and specific gene expression after cell exposure to dentin bonding agents. Therefore, we used primary human gingival fibroblasts to examine the effect of six dentin bonding agents on the expression of c-fos and c-jun protooncogenes to evaluate the genotoxicity/mutagenicity and cacinogenicity potential of the dentin bonding agents. The levels of mRNA were measured by the quantitative RT-PCR analysis. c-fos and c-jun mRNA expression in dentin bonding agents-treated cells revealed a rapid accumulation of the transcript, a significant signal first was detectable after 1h of exposure. Persistent induction of c-jun and c-fos protooncogenes by dentine bonding agents may distribute systemically to cause some unexpected adverse effects on human beings. It would be necessary to identify the severely toxic compounds and replace these substances by better biocompatible components. Otherwise, leaching of those genotoxicity/mutagenicity and cacinogenicity components must be minimized or prevented.

  18. Proton induced X-ray emission (PIXE) analysis of sources of porcelain body of Ru Guan and Jun Guan porcelains

    Institute of Scientific and Technical Information of China (English)

    LI Guoxia; ZHAO Wenjun; CHENG Huansheng; ZHAO Weijuan; LI Rongwu; SUN Hongwei; GUO Min; WANG Yanfang; LIU Hui; ZHAO Qingyun; SUN Xinmin

    2006-01-01

    34 samples of Ru Guan porcelain body and 50 samples of Jun Guan porcelain body (both kinds being in different body colors) were selected with the purpose of finding out the source of raw materials and their classification relationship so as to search for ways of non-destructive discrimination. Proton induced X-ray emission (PIXE) has been applied to these samples to determine their chemical elements. The data of seven major chemical elements collected from these samples were further studied through fuzzy cluster analysis. Results indicate that the origin of raw materials of Jun Guan porcelain body samples is comparatively more concentrated in certain places, while that of Ru Guan porcelain body samples is scattered about. The places of origin of raw materials of the majority of Ru Guan and Jun Guan porcelain body samples have something in common, but some differences still exist. It might be an important way for non-destructive discrimination among Ru Guan and Jun Guan porcelains by combining PIXE with fuzzy cluster analysis.

  19. MPTP-induced increase in c-Fos- and c-Jun-like immunoreactivity in the monkey cerebellum

    Directory of Open Access Journals (Sweden)

    D Necchi

    2009-06-01

    Full Text Available The transcription factors c-Fos and c-Jun have been described to be overexpressed following many pathological stimuli, but whether they are required for neurodegeneration or neuroprotection is still open. In the present report, we analyzed the role of c-Fos and c-Jun proteins in Purkinje cell degeneration caused by the neurotoxin MPTP (1-methyl-4- phenyl-1,2,3,6-tetrahydropyridine in the monkey cerebellum, and determined the neuroprotective effect of the antioxidant drug a-dihydroergocryptine (DHEC, whose prior and simultaneous administration reduced the MPTP-induced neuronal loss in the substantia nigra. Immunocytochemistry for c-Fos- and c-Jun-like proteins showed persistent increased staining in Purkinje cells of MPTP-treated monkeys. The staining was greatly reduced in animals receiving DHEC. Similar results were observed in white matter glial cells after immunoreaction for c-Fos. The results suggest that, at least as far as the cerebellum is concerned, the increase in c-Fos and c-Jun expression correlate with cell damage, rather than with preservation.

  20. MPTP-induced increase in c-Fos- and c-Jun-like immunoreactivity in the monkey cerebellum.

    Science.gov (United States)

    Necchi, Daniela; Soldani, C; Ronchetti, F; Bernocchi, G; Scherini, E

    2004-01-01

    The transcription factors c-Fos and c-Jun have been described to be overexpressed following many pathological stimuli, but whether they are required for neurodegeneration or neuroprotection is still open. In the present report, we analyzed the role of c-Fos and c-Jun proteins in Purkinje cell degeneration caused by the neurotoxin MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) in the monkey cerebellum, and determined the neuroprotective effect of the antioxidant drug a-dihydroergocryptine (DHEC), whose prior and simultaneous administration reduced the MPTP-induced neuronal loss in the substantia nigra. Immunocytochemistry for c-Fos- and c-Jun-like proteins showed persistent increased staining in Purkinje cells of MPTP-treated monkeys. The staining was greatly reduced in animals receiving DHEC. Similar results were observed in white matter glial cells after immunoreaction for c-Fos. The results suggest that, at least as far as the cerebellum is concerned, the increase in c-Fos and c-Jun expression correlate with cell damage, rather than with preservation.

  1. The proapoptotic dp5 gene is a direct target of the MLK-JNK-c-Jun pathway in sympathetic neurons.

    Science.gov (United States)

    Towers, Emily; Gilley, Jonathan; Randall, Rebecca; Hughes, Rosie; Kristiansen, Mark; Ham, Jonathan

    2009-05-01

    The death of sympathetic neurons after nerve growth factor (NGF) withdrawal requires de novo gene expression. Dp5 was one of the first NGF withdrawal-induced genes to be identified and it encodes a proapoptotic BH3-only member of the Bcl-2 family. To study how dp5 transcription is regulated by NGF withdrawal we cloned the regulatory regions of the rat dp5 gene and constructed a series of dp5-luciferase reporter plasmids. In microinjection experiments with sympathetic neurons we found that three regions of dp5 contribute to its induction after NGF withdrawal: the promoter, a conserved region in the single intron, and sequences in the 3' untranslated region of the dp5 mRNA. A construct containing all three regions is efficiently activated by NGF withdrawal and, like the endogenous dp5, its induction requires mixed-lineage kinase (MLK) and c-Jun N-terminal kinase (JNK) activity. JNKs phosphorylate the AP-1 transcription factor c-Jun, and thereby increase its activity. We identified a conserved ATF site in the dp5 promoter that binds c-Jun and ATF2, which is critical for dp5 promoter induction after NGF withdrawal. These results suggest that part of the mechanism by which the MLK-JNK-c-Jun pathway promotes neuronal apoptosis is by activating the transcription of the dp5 gene.

  2. Induction of c-Jun by air particulate matter (PM₁₀) of Mexico city: Participation of polycyclic aromatic hydrocarbons.

    Science.gov (United States)

    Salcido-Neyoy, Martha Estela; Sánchez-Pérez, Yesennia; Osornio-Vargas, Alvaro Román; Gonsebatt, María Eugenia; Meléndez-Zajgla, Jorge; Morales-Bárcenas, Rocío; Petrosyan, Pavel; Molina-Servin, Edith Danny; Vega, Elizabeth; Manzano-León, Natalia; García-Cuellar, Claudia M

    2015-08-01

    The carcinogenic potential of urban particulate matter (PM) has been partly attributed to polycyclic aromatic hydrocarbons (PAHs) content, which activates the aryl hydrocarbon receptor (AhR). Here we report the effect of PM with an aerodynamic size of 10 μm (PM10) on the induction of AhR pathway in A549 cells, evaluating its downstream targets CYP1B1, IL-6, IL-8 and c-Jun. Significant increases in CYP1B1 protein and enzyme activity; IL-6 and IL-8 secretion and c-Jun protein were found in response to PM10. The formation of PAH-DNA adducts was also detected. The involvement of AhR pathway was confirmed with Resveratrol as AhR antagonist, which reversed CYP1B1 and c-Jun induction. Nevertheless, in IL-6 and IL-8 secretion, the Resveratrol was ineffective, suggesting an effect independent of this pathway. Considering the role of c-Jun in oncogenesis, its induction by PM may be contributing to its carcinogenic potential through induction of AhR pathway by PAHs present in PM10.

  3. Regulation of Hippo signaling by Jun kinase signaling during compensatory cell proliferation and regeneration, and in neoplastic tumors.

    Science.gov (United States)

    Sun, Gongping; Irvine, Kenneth D

    2011-02-01

    When cells undergo apoptosis, they can stimulate the proliferation of nearby cells, a process referred to as compensatory cell proliferation. The stimulation of proliferation in response to tissue damage or removal is also central to epimorphic regeneration. The Hippo signaling pathway has emerged as an important regulator of growth during normal development and oncogenesis from Drosophila to humans. Here we show that induction of apoptosis in the Drosophila wing imaginal disc stimulates activation of the Hippo pathway transcription factor Yorkie in surviving and nearby cells, and that Yorkie is required for the ability of the wing to regenerate after genetic ablation of the wing primordia. Induction of apoptosis activates Yorkie through the Jun kinase pathway, and direct activation of Jun kinase signaling also promotes Yorkie activation in the wing disc. We also show that depletion of neoplastic tumor suppressor genes, including lethal giant larvae and discs large, or activation of aPKC, activates Yorkie through Jun kinase signaling, and that Jun kinase activation is necessary, but not sufficient, for the disruption of apical-basal polarity associated with loss of lethal giant larvae. Our observations identify Jnk signaling as a modulator of Hippo pathway activity in wing imaginal discs, and implicate Yorkie activation in compensatory cell proliferation and disc regeneration.

  4. CONTRIBUTION OF INSPIRATORY FLOW TO ACTIVATION OF EGFR, RAS, MAPK, ATF-2 AND C-JUN DURING LUNG STRETCH

    Science.gov (United States)

    Contribution of Inspiratory Flow to Activation of EGFR, Ras, MAPK, ATF-2 and c-Jun during Lung StretchR. Silbajoris 1, Z. Li 2, J. M. Samet 1 and Y. C. Huang 1. 1 NHEERL, ORD, US EPA, RTP, NC and 2 CEMALB, UNC-CH, Chapel Hill, NC . Mechanical ventilation with larg...

  5. Combined Expression of c-jun, c-fos, and p53 Improves Estimation of Prognosis in Oral Squamous Cell Carcinoma.

    Science.gov (United States)

    Wang, Shan; Xu, Xin; Xu, Fei; Meng, Yan; Sun, Changsheng; Shi, Lei; Zhao, Eryang

    2016-09-13

    To identify the prognostic value of c-jun, c-fos, and p53 in oral cancer, we examined the impact of immunohistochemical expression of these markers on tumor progression in 157 oral squamous cell carcinoma (OSCC). We found that c-jun or c-fos was significantly associated with lymph node metastasis, and coexpression of c-jun/c-fos, or c-jun/c-fos/p53 were significantly associated with lymph node metastasis, poor differentiation and clinical stage. The coexpression of c-jun/c-fos/p53 was identified as independent prognostic factors for overall survival. Simultaneous coexpression of these markers in OSCCs might prove to be a useful indicator for differentiation of low and high-risk patients.

  6. The ornithine decarboxylase, NO-synthase activities and phospho-c-Jun content under experimental gastric mucosa malignancy

    Directory of Open Access Journals (Sweden)

    Mariia Tymoshenko

    2016-04-01

    Full Text Available Ornithine decarboxylase is the first and key regulatory enzyme in synthesis of polyamines, which are essential for cell proliferation and differentiation, so its aberrant regulation is reported to play a role in neoplastic transformation and tumours growth. That's why, there were analysed some major links of metabolic pathways that are closely related to tumorigenesis: ornithine decarboxylase, and the NADPH-dependent enzyme nitric oxide synthase, the nuclear phosphoprotein c-Jun, that could play an important role in the development of gastric cancer malignancy.The gastric carcinogenesis was initiated in rats by 10-week replacement of drinking water by 0.01% N-methyl-N-nitro-N-nitrosoguanidine solution, at the same time they were redefined on the diet containing 5% NaCl. After this period expiry the animals were fed with standard diet till the end of the 24th week. The gastric mucosa cells were extracted at the end of the 4th, 6th, 8th, 10th, 12th, 18th and 24th week and underwent biochemical examinations. It was established the elevated phospho-c-Jun content, ornithine decarboxylase and inducible nitric oxide synthase activities from 6th to 24th week of gastric cancer development compared to the control references. The increasing of ornithine decarboxylase activity could probably be caused by the growth of phospho-c-Jun, it is also belonging to an ornithine decarboxylase transactivation effects. Thus, it was shown that the increase of ornithine decarboxylase and inducible nitric oxide synthase activities, phospho-c-Jun and nitrite-ions accumulation in gastric mucosa epithelial cells were associated with the gastric malignant progression. The complex relationships between the examined enzymes and transcription activator that pointed to an aggravation of pathological disturbances due to reciprocal action between ornithine decarboxylase and c-Jun and nitric oxide synthase participation. [Biomed Res Ther 2016; 3(4.000: 596-604

  7. Mkp1 is a c-Jun target gene that antagonizes JNK-dependent apoptosis in sympathetic neurons.

    Science.gov (United States)

    Kristiansen, Mark; Hughes, Rosie; Patel, Pritika; Jacques, Thomas S; Clark, Andrew R; Ham, Jonathan

    2010-08-11

    Developing sympathetic neurons depend on NGF for survival. When sympathetic neurons are deprived of NGF in vitro, a well documented series of events, including c-Jun N-terminal kinase (JNK) pathway activation, release of cytochrome c from the mitochondria, and caspase activation, culminates in the death of the neuron by apoptosis within 24-48 h. This process requires de novo gene expression, suggesting that increased expression of specific genes activates the cell death program. Using rat gene microarrays, we found that NGF withdrawal induces the expression of many genes, including mkp1, which encodes a MAPK phosphatase that can dephosphorylate JNKs. The increase in mkp1 mRNA level requires the MLK-JNK-c-Jun pathway, and we show that Mkp1 is an important regulator of JNK-dependent apoptosis in sympathetic neurons. In microinjection experiments, Mkp1 overexpression can inhibit JNK-mediated phosphorylation of c-Jun and protect sympathetic neurons from apoptosis, while Mkp1 knockdown accelerates NGF withdrawal-induced death. Accordingly, the number of superior cervical ganglion (SCG) neurons is reduced in mkp1-/- mice at P1 during the period of developmental sympathetic neuron death. We also show that c-Jun and ATF2 bind to two conserved ATF binding sites in the mkp1 promoter in vitro and in chromatin. Both of these ATF sites contribute to basal promoter activity and are required for mkp1 promoter induction after NGF withdrawal. These results demonstrate that Mkp1 is part of a negative feedback loop induced by the MLK-JNK-c-Jun signaling pathway that modulates JNK activity and the rate of neuronal death in rat sympathetic neurons following NGF withdrawal.

  8. 刍议CAI在体育教学中的互补作用%CAI's Supplementary Effect on Physical Training

    Institute of Scientific and Technical Information of China (English)

    黄晓文

    2003-01-01

    现代科学技术的迅速发展,尤其是计算机多媒体技术的出现、网络技术的运用,数字化信息时代的到来已给现代教学带来了深刻的变化;冲击着传统的教学模式、教学观念,引发教学方法和教学手段的改革.计算机辅助教学(Computer Assisted Instruction缩略:CAI,俗称:多媒体课件)是现代信息技术应用于教育的核心内容和主要技术手段.CAI作为一种新生的现代教学方法和手段,已广泛应用于教育教学的各个领域.然而,作为学校教育教学的重要组成部分的体育教学,无论是CAI在体育教学中的应用理论研究,还是在实践运用、软件开发与应用等方面都存在着相对滞后的局面,不能适应现代教育教学的根本需要.本文就CAI在学校对体育教学中的应用、影响因素、以及如何解决问题等方面作一些理论与实践相结合的探讨,以期推动中小学计算机辅助体育教学的发展.

  9. JunD Is Required for Proliferation of Prostate Cancer Cells and Plays a Role in Transforming Growth Factor-β (TGF-β)-induced Inhibition of Cell Proliferation.

    Science.gov (United States)

    Millena, Ana Cecilia; Vo, BaoHan T; Khan, Shafiq A

    2016-08-19

    TGF-β inhibits proliferation of prostate epithelial cells. However, prostate cancer cells in advanced stages become resistant to inhibitory effects of TGF-β. The intracellular signaling mechanisms involved in differential effects of TGF-β during different stages are largely unknown. Using cell line models, we have shown that TGF-β inhibits proliferation in normal (RWPE-1) and prostate cancer (DU145) cells but does not have any effect on proliferation of prostate cancer (PC3) cells. We have investigated the role of Jun family proteins (c-Jun, JunB, and JunD) in TGF-β effects on cell proliferation. Jun family members were expressed at different levels and responded differentially to TGF-β treatment. TGF-β effects on JunD protein levels, but not mRNA levels, correlated with its effects on cell proliferation. TGF-β induced significant reduction in JunD protein in RWPE-1 and DU145 cells but not in PC3 cells. Selective knockdown of JunD expression using siRNA in DU145 and PC3 cells resulted in significant reduction in cell proliferation, and forced overexpression of JunD increased the proliferation rate. On the other hand, knockdown of c-Jun or JunB had little, if any, effect on cell proliferation; overexpression of c-Jun and JunB decreased the proliferation rate in DU145 cells. Further studies showed that down-regulation of JunD in response to TGF-β treatment is mediated via the proteasomal degradation pathway. In conclusion, we show that specific Jun family members exert differential effects on proliferation in prostate cancer cells in response to TGF-β, and inhibition of cell proliferation by TGF-β requires degradation of JunD protein.

  10. Transoral approach to the craniovertebral junction Acesso transoral para a junção craniocervical

    Directory of Open Access Journals (Sweden)

    José Alberto Landeiro

    2007-12-01

    Full Text Available The transoral approach provides a safe exposure to lesions in the midline and the ventral side of the craniovertebral junction. The advantages of the transoral approach are 1 the impinging bony pathology and granulation tissue are accessible only via the ventral route; 2 the head is placed in the extended position, thus decreasing the angulation of the brainstem during the surgery; and 3 surgery is done through the avascular median pharyngeal raphe and clivus. We analyzed the clinical effects of odontoidectomy after treating 38 patients with basilar invagination. The anterior transoral operation to treat irreducible ventral compression in patients with basilar invagination was performed in 38 patients. The patients’ ages ranged from 34 to 67 years. Fourteen patients had associated Chiari malformation and eight had previously undergone posterior decompressive surgery. The main indication for surgery was significant neurological deterioration. Symptoms and signs included neck pain, myelopathy, lower cranial nerve dysfunction, nystagmus and gait disturbance. Extended exposure was performed in 24 patients. The surgery was beneficial to the majority of patients. There was one death within 10 days of surgery, due to pulmonary embolism. Postoperative complications included two cases of pneumonia, three cases of oronasal fistula with regurgitation and one cerebrospinal fluid leak. In patients with marked ventral compression, the transoral approach provides direct access to the anterior face of the craniovertebral junction and effective means for odontoidectomy.O acesso transoral é uma via direta e segura às lesões situadas na linha média e na face anterior da junção craniocervical. As vantagens do acesso transoral são as seguintes:1 a compressão óssea e o tecido de granulação localizam-se anteriormente e são accessíveis pela via anterior; 2 a cabeça do paciente é colocada em extensão, diminuindo a angulação do tronco cerebral durante

  11. JunB breakdown in mid-/late G2 is required for down-regulation of cyclin A2 levels and proper mitosis.

    Science.gov (United States)

    Farràs, Rosa; Baldin, Véronique; Gallach, Sandra; Acquaviva, Claire; Bossis, Guillaume; Jariel-Encontre, Isabelle; Piechaczyk, Marc

    2008-06-01

    JunB, a member of the AP-1 family of dimeric transcription factors, is best known as a cell proliferation inhibitor, a senescence inducer, and a tumor suppressor, although it also has been attributed a cell division-promoting activity. Its effects on the cell cycle have been studied mostly in G1 and S phases, whereas its role in G2 and M phases still is elusive. Using cell synchronization experiments, we show that JunB levels, which are high in S phase, drop during mid- to late G2 phase due to accelerated phosphorylation-dependent degradation by the proteasome. The forced expression of an ectopic JunB protein in late G2 phase indicates that JunB decay is necessary for the subsequent reduction of cyclin A2 levels in prometaphase, the latter event being essential for proper mitosis. Consistently, abnormal JunB expression in late G2 phase entails a variety of mitotic defects. As these aberrations may cause genetic instability, our findings contrast with the acknowledged tumor suppressor activity of JunB and reveal a mechanism by which the deregulation of JunB might contribute to tumorigenesis.

  12. 電腦輔助教學與個別教學結合: 電腦輔助教學課堂應用初探 Computer-Assisted Instruction Under the Management of Individualized Instruction: A Classroom Management Approach of CAI

    Directory of Open Access Journals (Sweden)

    Sunny S. J. Lin

    1988-03-01

    Full Text Available 無First reviews the development of Computer. Assisted Instruction (CAI in Taiwan. This study describes the training of teachers from different levels of schools to design CAI coursewares, and the planning of CAI courseware bank possesses 2,000 supplemental coursewares. Some CAI's c1assroom application system should be carefully established to prevent the easy abuse of a CAI courseware as an instructional plan. The study also claims to steer CAI in our elemantary and secondary education could rely on the mastery learning as the instructional plan. In this case, CAI must limit its role as the formative test and remedial material only. In the higher education , the Keller's Personalized System of Instruction could be an effective c1assroom management system. Therefore, CAI will offer study guide and formative test only. Using these 2 instructional system may enhance student's achievement , and speed up the learning rate at the same time. Combining with individualized instruction and CAI will be one of the most workable approach in current c1assroom . The author sets up an experiment 10 varify their effectiveness and efficiency in the near future.

  13. 试论钧瓷命名的理念和方法%Ideas and methods of naming Jun porcelain

    Institute of Scientific and Technical Information of China (English)

    李向平

    2012-01-01

    钧瓷在世界陶瓷史上享有独特而崇高的地位,体现着中国人"天人合一"的精神理念。钧瓷命名是以中国传统文化为依据,以艺术审美为手段,以哲学的、宗教的、艺术的语言为载体,将其文化内涵恰当地表示出来,这既是钧瓷营销之必需,又有引领人们发现美、享受美的作用。在多元化的社会背景下,钧瓷的命名不但要求造成产品之间的区别,而且还要凸显其亮点,产生"画龙点睛"、"点石成金"之功效,使人们产生美好的联想,寄予微妙的情趣,获得审美的愉悦。钧瓷命名的理念、方法和技巧体现在钧瓷企业、品牌及产品的命名上。%Jun porcelain has a unique and high status in the world of pottery history, and embodies the Chinese spiritual concept of "harmony between human being and nature". Jun porcelain is named after Chinese traditional culture as the basis, the art aesthetic as the method, the philosophy, religion and artistic language as the carrier, speaking out its cultural connotation properly, which is both essential for jun porcelain marketing and helpful for people to discover and enjoy beauty. In a social background of diversification, the naming of Jun porcelain not only requires to make the difference between products, but also highlights their features, produces the effect of "making the finishing point", so as to to make people produce good associations, expect the subtle appeal and get aesthetic pleasure. The ideas, methods and skills of naming Jun porcelain are reflected by the naming of Jun porcelain enterprises, brands and products.

  14. c-Jun-mediated β-1,3-N-acetylglucosaminyltransferase 8 expression: A novel mechanism regulating the invasion and metastasis of colorectal carcinoma cells.

    Science.gov (United States)

    Liu, Chunliang; Qiu, Hao; Yu, Meiyun; Wang, Zerong; Yuan, Yaqin; Jiang, Zhi; Shao, Xuejun; Hua, Dong; Liu, Min; Wu, Shiliang

    2017-09-01

    β-1,3-N-Acetylglucosaminyltransferase 8 (β3GnT8) is a key enzyme that catalyzes the formation of polylactosamine glycan structures by transferring GlcNAc to tetra-antennary β1-6-branched N-glycans, and it has been reported to participate in tumor invasion and metastasis by regulating the expression of matrix metalloproteinases (MMPs), cluster of differentiation 147 (CD147) and polylactosamine. By contrast, the role of transcription factor c-Jun in cell cycle progression has been well established. c-Jun has an important role in tumor cell invasion and metastasis. However, the precise molecular mechanisms by which c-Jun regulates these processes in colorectal carcinoma cells are not fully elucidated. In the present study, c-Jun had a significant effect on the invasive and migratory abilities of SW480 and LoVo cells. Additionally, overexpression of c-Jun was able to increase the expression of β3GnT8, MMPs, CD147 and polylactosamine. Similarly, knockdown of c-Jun was able to decrease the expression of β3GnT8, MMPs, CD147 and polylactosamine. These results suggest that c-Jun is able to regulate colorectal carcinoma cell invasion and metastasis via β3GnT8. A chromatin immunoprecipitation assay indicated that c-Jun is able to bind directly to the promoter regions of β3GnT8 in SW480 and LoVo cells. This leads to transcriptional activation of β3GnT8, which in turn regulates the expression of tumor invasion and metastasis-associated genes. The results of the present study demonstrate a novel mechanism underlying colorectal carcinoma cell invasion and metastasis, where β3GnT8 is transcriptionally activated via c-Jun binding to its promoter.

  15. The c-Fos and c-Jun from Litopenaeus vannamei play opposite roles in Vibrio parahaemolyticus and white spot syndrome virus infection.

    Science.gov (United States)

    Li, Chaozheng; Li, Haoyang; Wang, Sheng; Song, Xuan; Zhang, Zijian; Qian, Zhe; Zuo, Hongliang; Xu, Xiaopeng; Weng, Shaoping; He, Jianguo

    2015-09-01

    Growing evidence indicates that activator protein-1 (AP-1) plays a major role in stimulating the transcription of immune effector molecules in cellular response to an incredible array of stimuli, including growth factors, cytokines, cellular stresses and bacterial and viral infection. Here, we reported the isolation and characterization of a cDNA from Litopenaeus vannamei encoding the full-length c-Fos protein (named as Lvc-Fos). The predicted amino acid sequences of Lvc-Fos contained a basic-leucine zipper (bZIP) domain, which was characteristic of members of the AP-1 family. Immunoprecipitation and native-PAGE assays determined that Lvc-Fos could interact with the Lvc-Jun, a homolog of c-Jun family in L. vannamei, in a heterodimer manner. Further investigation demonstrated that Lvc-Fos and Lvc-Jun were expressed in all tested tissues and located in the nucleus. Real-time RT-PCR analysis showed both Lvc-Fos and Lvc-Jun in gills were up-regulated during Vibrio parahaemolyticus and white spot syndrome virus (WSSV) challenges. In addition, reporter gene assays indicated Lvc-Fos and Lvc-Jun could activate the expression of antimicrobial peptides (AMPs) of Drosophila and shrimp, as well as WSSV immediate early (IE) genes wsv069 and wsv249, in a different manner. Knockdown of Lvc-Fos or Lvc-Jun by RNA interference (RNAi) resulted in higher mortalities of L. vannamei after infection with V. parahaemolyticus, suggesting that Lvc-Fos and Lvc-Jun might play protective roles in bacterial infection. However, silencing of Lvc-Fos or Lvc-Jun in shrimp caused lower mortalities and virus loads under WSSV infection, suggesting that Lvc-Fos and Lvc-Jun could be engaged for WSSV replication and pathogenesis. In conclusion, our results provided experimental evidence and novel insight into the roles of L. vannamei AP-1 in bacterial and viral infection.

  16. The effects of vitamin E succinate on the expression of c-jun gene and protein in human gastric cancer SGC-7901 cells

    Institute of Scientific and Technical Information of China (English)

    Yan Zhao; Kun Wu; Wei Xia; Yu-Juan Shan; Li-Jie Wu; Wei-Ping Yu

    2002-01-01

    AIM: To investigate the effects of vitamin E succinate (VES) on the expression of c-jun gene and protein in human gastric cancer SGC-7901 cells.METHODS: After SGC-7901 cells were treated with VES at different doses (5,10,20 mg@L-1) at different time, reverse transcription-PCR technique was used to detect the level of c-jun mRNA; Western Blot was applied to measure the expression of c-jun protei n/RESULTS: After the cells were treated with VES at 20 mg@L-1 for 3 h, the expression rapidly reached its maximum that was 3.5 times of UT control (P<0.01). The level of c-jun mRNA was also increased following treatment of VES for 6 h.However, the expression after treatment of VES at 5 mg@L-1for 24 h was 1.6 times compared with UT control (P<0.01).Western blot analysis showed that the level of c-jun protein was obviously elevated in VES-treated SGC-7901 cells at 20 mg@L-1 for 3 h. The expression of c-jun protein was gradually increased after treatment of VES at 20 mg@L-1 for 3, 6, 12 and 24 h, respectively, with an evident time-effect relationship. CONCLUSION: The levels of c-jun mRNA and protein in VES-treated SGC-7901 cells were increased in a dose- and time-dependent manner; the expression of c-jun was prolonged by VES, indicating that c-jun is involved in VESinduced apoptosis in SGC-7901 cells.

  17. CAI Yuan-pei's Thoughts on Museum Aesthetic Education%蔡元培的博物馆美育思想研究

    Institute of Scientific and Technical Information of China (English)

    李竞艳

    2012-01-01

    著名的教育家、思想家蔡元培先生非常重视美育对培养健全人格以及促使人的全面发展的重要作用。他认为,在实施美育教育中,博物馆丰富的艺术藏品为美育教育提供了重要的物质基础;藏品的直观性成为美感的最佳培养形式;具有强烈融入感的博物馆陈列语言以及博物馆教育的公众性特征与美育教育的特点相得益彰。由此进一步认为博物馆是美育教育的重要媒介和载体之一。关注博物馆建设,既是关注社会美育教育的具体表现,同时也符合美育发展之公例。%Mr. CAI Yuan-pei, a notable educator and thinker of China, valued aesthetic education highly for the important role it plays in forming sound personalities and promoting integrated development of people. According to Cai, the artistic collections of museums provide important material base for aesthetic education, the direct viewing of objects offers the best approach to cultivate the appreciation of aesthetics, and the engaging narratives of displays and the public feature of museum education are in consonance with the characteristics of aesthetic education. Cai argued further that museums were an important medium and carrier of aesthetic education. Paying attention to museum development is a way to value social aesthetic education, which is in line with the principles of aesthetic education development.

  18. Transforming growth factor-β1 regulation of ATF-3, c-Jun and JunB proteins for activation of matrix metalloproteinase-13 gene in human breast cancer cells.

    Science.gov (United States)

    Gokulnath, M; Swetha, R; Thejaswini, G; Shilpa, P; Selvamurugan, N

    2017-01-01

    Transforming growth factor-beta1 (TGF-β1) plays a significant role in breast cancer mediated bone metastasis, and it stimulated expression of matrix metalloproteinase-13 (MMP-13; an invasive and metastasis gene) via activating transcription factor-3 (ATF-3) in human breast cancer cells (MDA-MB231). We further dissected the role of ATF-3 and its interacting proteins (activator protein-1; AP-1) for TGF-β1-stimulation of MMP-13 expression in these cells. Chromatin immunoprecipitation (ChIP) experiment identified the TGF-β1-stimulation of ATF-3 interaction at the AP-1 site of the MMP-13 promoter in a sustained and prolonged manner in MDA-MB231 cells. In silico protein-protein interaction, co-immunoprecipitation and western blot experiments identified the ATF-3 interaction and regulation of c-Jun and JunB proteins in these cells. The sequential ChIP assay confirmed the presence of c-Jun/ATF-3 complex at the AP-1 site of the MMP-13 promoter in MDA-MB231 cells upon TGF-β1-treatment. Hence, our results suggested that TGF-β1-treatment stimulated a sustained and prolonged expression of ATF-3, and its interaction and regulation of c-Jun protein and their assembly as a protein complex at the AP-1 site of the MMP-13 promoter could be responsible for MMP-13 gene activation in MDA-MB231 cells. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Coptidis rhizome and Si Jun Zi Tang can prevent Salmonella enterica serovar Typhimurium infection in mice.

    Directory of Open Access Journals (Sweden)

    Chiung-Hung Chang

    Full Text Available Salmonella, a common zoonotic pathogen, causes gastroenteritis in both humans and animals. Traditional Chinese Medicine (TCM has been used to improve gastrointestinal dysfunction and to modify the immune response to inflammation for centuries. This study used six herbal plants and four TCM formulae to rate their efficacy in preventing S. Typhimurium infection via mouse model. Minimum bactericidal concentration (MBC of Coptidis rhizome (CR against the reference strain tallied 12.5 mg/ml and against clinical isolate ST21 was 25 mg/ml. MBCs of other herbal extracts and formulae on Salmonella Typhimurium strains were above 50 mg/ml. In the mice model, CR and Si Jun Zi Tang (SJZT could significantly decrease the bacterial load in organs and blood after being challenged, along with body weight loss due to the infection. CR and SJZT alleviated infection-induced interferon-gamma levels in the serum and tissues, and tumor necrosis factor-alpha (TNF-α levels in intestinal tissues. CR and SJZT serum metabolites could suppress S. Typhimurium invasion and TNF-α expression in RAW264.7 cells. The therapeutic activity of CR and SJZT may involve berberine, ginsenoside Rb1, and glycyrrhizin, interfering with Salmonella when invading macrophages. CR and SJZT has shown potential in preventing S. Typhimurium infection through the regulation of the immune response.

  20. Jun N-Terminal Protein Kinase Enhances Middle Ear Mucosal Proliferation during Bacterial Otitis Media▿

    Science.gov (United States)

    Furukawa, Masayuki; Ebmeyer, Jörg; Pak, Kwang; Austin, Darrell A.; Melhus, Åsa; Webster, Nicholas J. G.; Ryan, Allen F.

    2007-01-01

    Mucosal hyperplasia is a characteristic component of otitis media. The present study investigated the participation of signaling via the Jun N-terminal protein kinase (JNK) mitogen-activated protein kinase in middle ear mucosal hyperplasia in animal models of bacterial otitis media. Otitis media was induced by the inoculation of nontypeable Haemophilus influenzae into the middle ear cavity. Western blotting revealed that phosphorylation of JNK isoforms in the middle ear mucosa preceded but paralleled mucosal hyperplasia in this in vivo rat model. Nuclear JNK phosphorylation was observed in many cells of both the mucosal epithelium and stroma by immunohistochemistry. In an in vitro model of primary rat middle ear mucosal explants, bacterially induced mucosal growth was blocked by the Rac/Cdc42 inhibitor Clostridium difficile toxin B, the mixed-lineage kinase inhibitor CEP11004, and the JNK inhibitor SP600125. Finally, the JNK inhibitor SP600125 significantly inhibited mucosal hyperplasia during in vivo bacterial otitis media in guinea pigs. Inhibition of JNK in vivo resulted in a diminished proliferative response, as shown by a local decrease in proliferating cell nuclear antigen protein expression by immunohistochemistry. We conclude that activation of JNK is a critical pathway for bacterially induced mucosal hyperplasia during otitis media, influencing tissue proliferation. PMID:17325051

  1. Coptidis rhizome and Si Jun Zi Tang can prevent Salmonella enterica serovar Typhimurium infection in mice.

    Science.gov (United States)

    Chang, Chiung-Hung; Yu, Bi; Su, Chiu-Hsian; Chen, Daniel S; Hou, Yu-Chi; Chen, Yueh-Sheng; Hsu, Yuan-Man

    2014-01-01

    Salmonella, a common zoonotic pathogen, causes gastroenteritis in both humans and animals. Traditional Chinese Medicine (TCM) has been used to improve gastrointestinal dysfunction and to modify the immune response to inflammation for centuries. This study used six herbal plants and four TCM formulae to rate their efficacy in preventing S. Typhimurium infection via mouse model. Minimum bactericidal concentration (MBC) of Coptidis rhizome (CR) against the reference strain tallied 12.5 mg/ml and against clinical isolate ST21 was 25 mg/ml. MBCs of other herbal extracts and formulae on Salmonella Typhimurium strains were above 50 mg/ml. In the mice model, CR and Si Jun Zi Tang (SJZT) could significantly decrease the bacterial load in organs and blood after being challenged, along with body weight loss due to the infection. CR and SJZT alleviated infection-induced interferon-gamma levels in the serum and tissues, and tumor necrosis factor-alpha (TNF-α) levels in intestinal tissues. CR and SJZT serum metabolites could suppress S. Typhimurium invasion and TNF-α expression in RAW264.7 cells. The therapeutic activity of CR and SJZT may involve berberine, ginsenoside Rb1, and glycyrrhizin, interfering with Salmonella when invading macrophages. CR and SJZT has shown potential in preventing S. Typhimurium infection through the regulation of the immune response.

  2. c-Jun-N-Terminal Kinase Signaling Is Involved in Cyclosporine-Induced Epithelial Phenotypic Changes

    Directory of Open Access Journals (Sweden)

    Nicolas Pallet

    2012-01-01

    Full Text Available Tubular epithelial cells play a central role in the pathogenesis of chronic nephropathies. Previous toxicogenomic studies have demonstrated that cyclosporine- (CsA- induced epithelial phenotypic changes (EPCs are reminiscent of an incomplete epithelial to mesenchymal transition (EMT in a TGF-β-independent manner. Furthermore, we identified endoplasmic reticulum (ER stress as a potential mechanism that may participate in the modulation of tubular cell plasticity during CsA exposure. Because c-jun-N-terminal kinase (JNK, which is activated during ER stress, is implicated in kidney fibrogenesis, we undertook the current study to identify the role of JNK signaling in EPCs induced by CsA. In primary cultures of human renal epithelial cells, CsA activates JNK signaling, and the treatment with a JNK inhibitor reduces the occurrence of cell shape changes, E-cadherin downregulation, cell migration, and Snail-1 expression. Our results suggest that CsA activates JNK signaling, which, in turn, may participate in the morphological alterations through the regulation of Snail-1 expression.

  3. Professor Jun Zhou's Life Choice and Celebration of His 80th Birthday

    Institute of Scientific and Technical Information of China (English)

    2012-01-01

    Professor Jun Zhou, an Academician of Chinese Academy of Sciences, is a phytochemist and medicinal chemist in China. He is a major founder for the estab- lishment of State Key Laboratory of Phytochemistry and Plant Resource in West China. The special issue of Chinese Journal of Chemistly is dedicated to his 80th birthday. Professor Zhou was born in Dongtai (Jiangsu prov- ince, China) in 1932, where he received his elementary education. He went to Nantong in 1946 to obtain his junior middle school education, and then he went to Nanjing in 1948 to receive his technical secondary school education at National Pharmaceutical School (the predecessor of China Phammceutical University). After graduation in 1951, he was appointed as a chief of Hu- man Resource Department at East China Pharmaceutical College and then served as a pharmacist at East China Health Bureau. He received his Bachelor's degree in the major of pharmaceutical engineering in 1958 fi'om East China Institute of Chemical Technology (the predeces- sor of East China University of Science and Technol- ogy).

  4. Potent inhibition of Junín virus infection by interferon in murine cells.

    Science.gov (United States)

    Huang, Cheng; Walker, Aida G; Grant, Ashley M; Kolokoltsova, Olga A; Yun, Nadezhda E; Seregin, Alexey V; Paessler, Slobodan

    2014-06-01

    The new world arenavirus Junín virus (JUNV) is the causative agent of Argentine hemorrhagic fever, a lethal human infectious disease. Adult laboratory mice are generally resistant to peripheral infection by JUNV. The mechanism underlying the mouse resistance to JUNV infection is largely unknown. We have reported that interferon receptor knockout mice succumb to JUNV infection, indicating the critical role of interferon in restricting JUNV infection in mice. Here we report that the pathogenic and vaccine strains of JUNV were highly sensitive to interferon in murine primary cells. Treatment with low concentrations of interferon abrogated viral NP protein expression in murine cells. The replication of both JUNVs was enhanced in IRF3/IRF7 deficient cells. In addition, the vaccine strain of JUNV displayed impaired growth in primary murine cells. Our data suggested a direct and potent role of host interferon response in restricting JUNV replication in mice. The defect in viral growth for vaccine JUNV might also partially explain its attenuation in mice.

  5. The roles of c-Jun NH2-terminal kinases (JNKs) in obesity and insulin resistance.

    Science.gov (United States)

    Pal, Martin; Febbraio, Mark A; Lancaster, Graeme I

    2016-01-15

    Obesity is currently at epidemic levels worldwide and is associated with a wide range of diseases such as type 2 diabetes, cardiovascular disease, fatty liver disease and certain forms of cancer. Obesity-induced chronic inflammation is central to the disrupted metabolic homeostasis which underlies many of these conditions. While research over the past decade has identified many of the cells and signalling molecules that contribute to obesity-induced inflammation, perhaps the best characterised are the stress-activated c-Jun NH2 -terminal kinases (JNKs). JNKs are activated in obesity in numerous metabolically important cells and tissues such as adipose tissue, macrophages, liver, skeletal muscle and regions of the brain and pituitary. Elegant in vivo mouse studies using Cre-LoxP-mediated recombination of the JNK1 and JNK2 genes have revealed the remarkably diverse roles that JNKs play in the development of obesity-induced inflammation, impaired glucose homeostasis and hepatic steatosis. While JNK activation in classical metabolically active tissues such as skeletal muscle and adipose tissue only appears to play a minor role on the induction of the above-mentioned pathologies, recent studies have clearly established the important roles JNK signalling fulfils in macrophages, the liver and cells of the anterior pituitary. Collectively, these studies place JNKs as important mediators of obesity and obesity-associated disruptions to metabolic homeostasis. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

  6. Cadmium promotes breast cancer cell proliferation by potentiating the interaction between ERalpha and c-Jun.

    Science.gov (United States)

    Siewit, Christina L; Gengler, Bridget; Vegas, Esera; Puckett, Rachel; Louie, Maggie C

    2010-05-01

    Cadmium is an environmental contaminant that enters the body through diet or cigarette smoke. It affects multiple cellular processes, including cell proliferation, differentiation, and apoptosis. Recently, cadmium has been shown to function as an endocrine disruptor, to stimulate estrogen receptor alpha (ERalpha) activity and promote uterine and mammary gland growth in mice. Although cadmium exposure has been associated with the development of breast cancer, the mechanism of action of cadmium remains unclear. To address this deficit, we examined the effects of cadmium treatment on breast cancer cells. We found that ERalpha is required for both cadmium-induced cell growth and modulation of gene expression. We also determined that ERalpha translocates to the nucleus in response to cadmium exposure. Additionally, we provide evidence that cadmium potentiates the interaction between ERalpha and c-Jun and enhances recruitment of this transcription factor complex to the proximal promoters of cyclin D1 and c-myc, thus increasing their expression. This study provides a mechanistic link between cadmium exposure and ERalpha and demonstrates that cadmium plays an important role in the promotion of breast cancer.

  7. Effect of growth hormone and serum on the expression of the proto-oncogenes c-jun and c-fos in insulin producing cells

    DEFF Research Database (Denmark)

    Petersen, Elisabeth D.; Billestrup, N; Nielsen, Jens Høiriis

    1990-01-01

    Expression of the proto-oncogenes c-fos and c-jun was analysed in the insulin producing rat tumor cell line, RIN 5AH. Addition of fetal calf serum (FCS) to serum-starved cells in the presence of cycloheximid induced a modest increase in c-fos and c-jun mRNA levels, whereas growth hormone (GH......RNA levels. These results suggest that the effects of GH on insulin producing cells are not mediated by activation of c-fos and c-jun transcription....

  8. Sexual life and sexual wellness in individuals with complete androgen insensitivity syndrome (CAIS) and Mayer-Rokitansky-Küster-Hauser Syndrome (MRKHS).

    Science.gov (United States)

    Fliegner, Maike; Krupp, Kerstin; Brunner, Franziska; Rall, Katharina; Brucker, Sara Y; Briken, Peer; Richter-Appelt, Hertha

    2014-03-01

    Sexual wellness depends on a person's physical and psychological constitution. Complete Androgen Insensitivity Syndrome (CAIS) and Mayer-Rokitansky-Küster-Hauser Syndrome (MRKHS) can compromise sexual well-being. To compare sexual well-being in CAIS and MRKHS using multiple measures: To assess sexual problems and perceived distress. To gain insight into participants' feelings of inadequacy in social and sexual situations, level of self-esteem and depression. To determine how these psychological factors relate to sexual (dys)function. To uncover what participants see as the source of their sexual problems. Data were collected using a paper-and-pencil questionnaire. Eleven individuals with CAIS and 49 with MRKHS with/without neovagina treatment were included. Rates of sexual dysfunctions, overall sexual function, feelings of inadequacy in social and sexual situations, self-esteem and depression scores were calculated. Categorizations were used to identify critical cases. Correlations between psychological variables and sexual function were computed. Sexually active subjects were compared with sexually not active participants. A qualitative content analysis was carried out to explore causes of sexual problems. An extended list of sexual problems based on the Diagnostic and Statistical Manual of Mental Disorders, 4th ed., text revision, by the American Psychiatric Association and related distress. Female Sexual Function Index (FSFI), German Questionnaire on Feelings of Inadequacy in Social and Sexual Situations (FUSS social scale, FUSS sexual scale), Rosenberg Self-Esteem Scale (RSE), Brief Symptom Inventory (BSI) subscale depression. Open question on alleged causes of sexual problems. The results point to a far-reaching lack of sexual confidence and sexual satisfaction in CAIS. In MRKHS apprehension in sexual situations is a source of distress, but sexual problems seem to be more focused on issues of vaginal functioning. MRKHS women report being satisfied with their

  9. CAI Courseware Designing Based on Constructivism%基于建构主义学习理论的CAI课件设计

    Institute of Scientific and Technical Information of China (English)

    李春艳; 王凡; 张积东

    2001-01-01

    CAI(Computer Assisted Instruction) is effective means in instruction field and will be used more and more. Meanwhile constructivism is a kind of theory that much accords with men's cognition regularity.So the combination of the both is a beneficial exploration.%CAI是广泛使用且行之有效的教学辅助手段,而建构主义是更符合人类认知规律的一种学习理论。两者的结合是新型的CAI课件设计的有益探索。

  10. The regulation of p53 up-regulated modulator of apoptosis by JNK/c-Jun pathway in β-amyloid-induced neuron death.

    Science.gov (United States)

    Akhter, Rumana; Sanphui, Priyankar; Das, Hrishita; Saha, Pampa; Biswas, Subhas Chandra

    2015-09-01

    Neuronal loss in selective areas of brain underlies the pathology of Alzheimer's disease (AD). Recent evidences place oligomeric β-amyloid (Aβ) central to the disease. However, mechanism of neuron death in response to Aβ remains elusive. Activation of the c-Jun N-terminal kinase (JNK) pathway and induction of the AP-1 transcription factor c-Jun are reported in AD. However, targets of JNK/c-Jun in Aβ-induced neuron death are mostly unknown. Our study shows that pro-apoptotic proteins, Bim (Bcl-2 interacting mediator of cell death) and Puma (p53 up-regulated modulator of apoptosis) are targets of c-Jun in Aβ-treated neurons. We demonstrate that the JNK/c-Jun pathway is activated, in cultures of cortical neurons following treatment with oligomeric Aβ and in AD transgenic mice, and that inhibition of this pathway by selective inhibitor blocks induction of Puma by Aβ. We also find that both JNK and p53 pathways co-operatively regulate Puma expression in Aβ-treated neurons. Moreover, we identified a novel AP1-binding site on rat puma gene which is necessary for direct binding of c-Jun with Puma promoter. Finally, we find that knocking down of c-Jun by siRNA provides significant protection from Aβ toxicity and that induction of Bim and Puma by Aβ in neurons requires c-Jun. Taken together, our results suggest that both Bim and Puma are target of c-Jun and elucidate the intricate regulation of Puma expression by JNK/c-Jun and p53 pathways in neurons upon Aβ toxicity. JNK/c-Jun pathway is shown to be activated in neurons of the Alzheimer's disease (AD) brain and plays a vital role in neuron death in AD models. However, downstream targets of c-Jun in this disease have not been thoroughly elucidated. Our study shows that two important pro-apoptotic proteins, Bim (Bcl-2 interacting mediator of cell death) and Puma (p53 up-regulated modulator of apoptosis) are targets of c-Jun in Aβ-treated neurons. We demonstrate that the JNK/c-jun pathway is activated, in cultures

  11. Striatal overexpression of DeltaJunD resets L-DOPA-induced dyskinesia in a primate model of Parkinson disease.

    Science.gov (United States)

    Berton, Olivier; Guigoni, Céline; Li, Qin; Bioulac, Bernard H; Aubert, Incarnation; Gross, Christian E; Dileone, Ralph J; Nestler, Eric J; Bezard, Erwan

    2009-09-15

    Involuntary movements, or dyskinesia, represent a debilitating complication of dopamine replacement therapy for Parkinson disease (PD). The transcription factor DeltaFosB accumulates in the denervated striatum and dimerizes primarily with JunD upon repeated L-3,4-dihydroxyphenylalanine (L-DOPA) administration. Previous studies in rodents have shown that striatal DeltaFosB levels accurately predict dyskinesia severity and indicate that this transcription factor may play a causal role in the dyskinesia sensitization process. We asked whether the correlation previously established in rodents extends to the best nonhuman primate model of PD, the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned macaque. We used western blotting and quantitative polymerase chain reaction (PCR) to compare DeltaFosB protein and messenger RNA (mRNA) levels across two subpopulations of macaques with differential dyskinesia severity. Second, we tested the causal implication of DeltaFosB in this primate model. Serotype 2 adeno-associated virus (AAV2) vectors were used to overexpress, within the motor striatum, either DeltaFosB or DeltaJunD, a truncated variant of JunD lacking a transactivation domain and therefore acting as a dominant negative inhibitor of DeltaFosB. A linear relationship was observed between endogenous striatal levels of DeltaFosB and the severity of dyskinesia in Parkinsonian macaques treated with L-DOPA. Viral overexpression of DeltaFosB did not alter dyskinesia severity in animals previously rendered dyskinetic, whereas the overexpression of DeltaJunD dramatically dropped the severity of this side effect of L-DOPA without altering the antiparkinsonian activity of the treatment. These results establish a mechanism of dyskinesia induction and maintenance by L-DOPA and validate a strategy, with strong translational potential, to deprime the L-DOPA-treated brain.

  12. Fibroin and Sericin from Bombyx mori Silk Stimulate Cell Migration through Upregulation and Phosphorylation of c-Jun

    Science.gov (United States)

    García-Vizcaíno, Eva María; Alcaraz, Antonia; Cenis, José Luis; Nicolás, Francisco José

    2012-01-01

    Wound healing is a biological process directed to the restoration of tissue that has suffered an injury. An important phase of wound healing is the generation of a basal epithelium able to wholly replace the epidermis of the wound. A broad range of products derived from fibroin and sericin from Bombyx mori silk are used to stimulate wound healing. However, so far the molecular mechanism underlying this phenomenon has not been elucidated. The aim of this work was to determine the molecular basis underlying wound healing properties of silk proteins using a cell model. For this purpose, we assayed fibroin and sericin in a wound healing scratch assay using MDA-MB-231 and Mv1Lu cells. Both proteins stimulated cell migration. Furthermore, treatment with sericin and fibroin involved key factors of the wound healing process such as upregulation of c-Jun and c-Jun protein phosphorylation. Moreover, fibroin and sericin stimulated the phosphorylation of ERK 1/2 and JNK 1/2 kinases. All these experiments were done in the presence of specific inhibitors for some of the cell signalling pathways referred above. The obtained results revealed that MEK, JNK and PI3K pathways are involved in fibroin and sericin stimulated cells migration. Inhibition of these three kinases prevented c-Jun upregulation and phosphorylation by fibroin or sericin. Fibroin and sericin were tested in the human keratinocyte cell line, HaCaT, with similar results. Altogether, our results showed that fibroin and sericin initiate cell migration by activating the MEK, JNK and PI3K signalling pathways ending in c-Jun activation. PMID:22860103

  13. 土壤链霉菌CaiF1抗菌物质的分离纯化及活性研究%Studies on Purification and Activity of Antibacterial Substances Derived from Soil Streptomyces sp.CaiF1

    Institute of Scientific and Technical Information of China (English)

    杨辉; 张茜; 曾建民; 李少华; 谭志远

    2011-01-01

    [Objective] Purification and activity of antibacterial substances derived from soil Streptomyces sp. CaiFl were studied. [Method] The antibacterial substances were separated and purified by Ethyl acetate extraction, macroporous adsorptive resin, silica gel chromatography and preparative high performance liquid chromatography (HPLC) , taking Staphylococcus aureus and Powdery mildew as activity indicating bacterial. [ Result ] Antibacterial substances were purified and the stability analysis of the extracts form Streptomyces CaiFl fermentation broth showed stable at pH 2.0 - 10.0, 100 ℃. And changed very little under UV treatment for 24 h. Inhibition rate of powdery mildew was 98.37%. [Conclusion] The purified antibacterial substances showed good stability, which provided theoretical foundation for their structural identifications and future applications.%[目的 ]从土壤链霉菌CaiF1发酵液中分离纯化抗菌物质,并研究该物质的活性.[方法] 采用乙酸乙酯萃取、大孔吸附树脂吸附、硅胶层析和制备型高效液相色谱(HPLC)等分离技术纯化抗菌物质,以金黄色葡萄球菌、白粉病菌为指示菌进行活性研究.[结果] 土壤链霉菌CaiF1发酵液中抗菌物质得到分离纯化;该物质在pH 2.0~10.0、100℃和紫外照射24h条件下抑菌活性几乎不变,对白粉病的防治效果达69.7%.[结论] 分离纯化的土壤链霉菌CaiF1抗菌物质具有很好的稳定性,为其结构鉴定和开发应用提供理论依据.

  14. CAI大学语文课件的选题与制作%Research and production of Chinese University of CAI courseware

    Institute of Scientific and Technical Information of China (English)

    陈利

    2014-01-01

    将CAI技术引入到大学语文教学中,可以提高教师的教学水平和学生的学习兴趣。针对CAI语文教学,该课题论述了CAI大学语文课件的文本、动画等教学素材的采集及制作技术,课件的开发平台是Authorwares7.0,其中还会用到动画素材编辑软件Flash MX,图像处理软件Photoshop 7.0等多种软件,与硬件相结合制作出高效实用的CAI课件辅助教学。%The CAI technology into the University Chinese teaching,can improve the teaching level of teachers andstudents' interest in learning.According to the CAI language teaching,this paper discusses the acquisition of CAIUniversity courseware for Chinese text,animation and other teaching materials and production technology,courseware development platform is the Authorwares7.0,which will use the animation editing software Flash MX,image processing software Photoshop 7 and many kinds of software,combined with the hardware to produce CAIcourseware to assist teaching efficiency the utility of the.

  15. Comparative Study on Cloud Parameter Estimation Among GOSAT/CAI, MODIS, CALIPSO/CALIOP and Landsat-8/OLI with Laser Radar: Lidar as Truth Data

    Directory of Open Access Journals (Sweden)

    Kohei Arai

    2016-10-01

    Full Text Available A comparative study on cloud parameter estimation among GOSAT/CAI, MODIS, CALIPSO/CALIOP and Landsat-8/OLI is carried out using Laser Radar: Lidar as a truth data. Optical depth, size distribution, as well as cirrus type of clouds are cloud parameters. In particular, cirrus cloud detection is tough issue. 1.38 µm channel is required for its detection. Although MODIS and Landsat-8/OLI have such channel, the other mission instruments, CAI and CALIPSO/CALIOP do not have such channel. As a truth data of cloud parameter, ground based Lidar is used in this comparative study. From the Lidar, backscattered echo signal and depolarization coefficient are obtained as a function of altitude. Therefore, cloud type, vertical profile can be derived from the Lidar data. CALIPSO/CALIOP is satellite based Lidar which allows observation of clouds from space. Although the directions of laser light emissions between CALIPSO/CALIOP and the ground based Lidar are different, their principles are same. Therefore, it is expected that CALIPSO/CALIOP data derived cloud parameters are similar to the ground based Lidar data derived cloud parameters. The experimental results show the aforementioned facts and are useful for improvement of cloud parameter estimation accuracy with several sensor data combinations.

  16. The possibility of controlled auto-ignition (CAI) in gasoline engine and gas to liquid (GTL) as a fuel of diesel engine in Korea

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, D. [Korea Inst. of Machinery and Materials, Daejou (Korea)

    2005-07-01

    A significant challenge grows from the ever-increasing demands for the optimization of performance, emissions, fuel economy and drivability. The most powerful technologies in the near future to improve these factors are believed Controlled Auto-Ignition (CAI) in gasoline engine and Gas to Liquid (GTL) as a fuel of Diesel engine. In recent years there has been an increasing trend to use more complex valvetrain designs from traditional camshaft driven mechanical systems to camless electromagnetic or electrohydraulic solutions. Comparing to fixed valve actuation systems, variable valve actuation (VVA) should be powerful to optimize the engine cycle. The matching of valve events to the engine performance and to emission requirements at a given engine or vehicle operating condition can be further optimized to the Controlled Auto-Ignition (CAI) in gasoline engine, which has benefits in NOx emission, fuel consumption, combustion stability and intake throttle load. In case of Diesel engine, the increasing demands for NOx and soot emission reduction have introduced aftertreatment technologies recently, but been in need of basic solution for the future, such as a super clean fuel like Gas to Liquid (GTL), which has benefits in comparability to diesel fuel, independency from crude oil and reduction of CO, THC and soot emissions. Korea looks to the future with these kinds of technologies, and tries to find the possibility for reaching the future targets in the internal combustion engine. (orig.)

  17. Analysis of Visual Basic and physical design of multimedia CAI courseware%解析Visual Basic与体育多媒体CAI课件设计

    Institute of Scientific and Technical Information of China (English)

    张雷

    2014-01-01

    Visual Basic(VB)语言是一门专业的软件开发工具,应用VB开发体育多媒体CAI软件能够有效提升课件的水准。当前体育多媒体CAI课件已经与VB密不可分,用VB开发工具来提升多媒体课件的水平已经成为未来发展的必然趋势。本文将重点探讨VB如何在课件中应用。%Visual Basic (VB) language is a professional software development tools,the application of VB in the development of Sports Multimedia CAI software can effectively improve the level of courseware. The current sports multimedia CAI courseware with VB are inseparable,to enhance the multimedia courseware development tools with VB level has become the inevitable trend of future development.This paper will focus on how to use VB in the courseware.

  18. Estructura del macrobentos de la laguna de Paca, Junín

    Directory of Open Access Journals (Sweden)

    Pedro Huamán

    2013-06-01

    Full Text Available Se caracterizó la estructura comunitaria del macrobentos de la laguna de Paca ubicada a 3364 msnm, a 11º 45 S y 75º 30’ W en el departamento de Junín-Perú. También se analizaron los principales factores físicos y químicos del agua y sedimentos que condicionan dicha estructura. Los muestreos se realizaron en el año 2000 en 8 estaciones, distribuidas en la zona litoral (5 y pelágica (3. En cada estación se tomaron muestras de agua cercana al fondo y de sedimentos para analizar los parámetros físicos, químicos y biológicos de la comunidad del macrobentos. Los datos fueron sometidos a pruebas univariadas y multivariadas para determinar el grado de interacción de los diversos factores con las variables biológicas. La diversidad del macrobentos es baja y muestra valores de diversidad menores a 1,5 y el número de especies menores a 11 especies. La abundancia varía en valores que van desde los 16 hasta 176 individuos/0,04 m2 . Tubifex tubifex y Chironomus sp. fueron las especies más resistentes a los altos valores de materia orgánica (35,22 a 38,28% y bajos valores de oxígeno disuelto (1 a 2 mg/L, lo que constituye indicadores biológicos de eutroficación.

  19. Je-Chun-Jun induced apoptosis of human cervical carcinoma HeLa cells

    Institute of Scientific and Technical Information of China (English)

    Han-jung CHAE; Kyung-mi PARK; Geun-youn LEE; Gi-seup JEONG; Hyung-rae PARK; Hyung-min KIM; Soo-wan CHAE; Shim-keun YOO; Hyung-ryong KIM

    2004-01-01

    AIM: To study the mechanism of Je-Chun-Jun (JCJ)-inducing the apoptosis of the human cervical carcinoma,HeLa cells. METHODS: The cell viability was assessed using MTT assay. The optical density was measured at 570 nm. The caspase activity was measured using 50 mmol/L of fluorogenic substrate, AC-DEVD-AMC (caspase3), AC-VEID-AMC (caspase-8) or AC-LEHD-AFC (caspase-9). To confirm the expression of proteins, Western blotting was performed. To detect the characteristic of apoptosis chromatin condensation, HeLa cells were stained with Hoechst 33258 in the presence of JCJ. For the cell cycle analysis, HeLa cells were incubated with Propidium iodide (PI) solution. Fluorescence intensity of cell cycle was measured using flow cytometry system. RESULTS:The loss of viability occurred following the exposure of 10 g/L JCJ. Cells treated with 10 g/L JCJ for 3 d exhibited the apoptotic morphology (brightly blue-fluorescent condensed nuclei by Hoechst 33258-staining) and the reduction of cell volume. Cells incubated with JCJ for 48 h were arrested at the G1 phase of cell cycle and their G1 checkpoint related gene products such as cyclin D1 were transiently decreased. We showed that JCJ induced the p38 MAPK activation in HeLa cells. The p38 MAPK inhibitor, SB203580 protected Hela cells from the JCJ-induced death as well as intervened the JCJ-induced accumulation of cells at the G1 phase. In contrast, MEK1 (-ERK upstream) inhibitor, PD98059 had no effect on HeLa cells. CONCLUSION: JCJ induced cell cycle arrest and apoptosis of HeLa cells through p38 MAPK pathway.

  20. Resveratrol increases anti-aging Klotho gene expression via the activating transcription factor 3/c-Jun complex-mediated signaling pathway.

    Science.gov (United States)

    Hsu, Shih-Che; Huang, Shih-Ming; Chen, Ann; Sun, Chiao-Yin; Lin, Shih-Hua; Chen, Jin-Shuen; Liu, Shu-Ting; Hsu, Yu-Juei

    2014-08-01

    The Klotho gene functions as an aging suppressor gene. Evidence from animal models suggests that induction of Klotho expression may be a potential treatment for age-associated diseases. However, the molecular mechanism involved in regulating renal Klotho gene expression remains unclear. In this study, we determined that resveratrol, a natural polyphenol, induced renal Klotho expression both in vivo and in vitro. In the mouse kidney, resveratrol administration markedly increased both Klotho mRNA and protein expression. In resveratrol-treated NRK-52E cells, increased Klotho expression was accompanied by the upregulation and nuclear translocation of activating transcription factor 3 (ATF3) and c-Jun. ATF3 or c-Jun overexpression enhanced the transcriptional activation of Klotho. Conversely, resveratrol-induced Klotho expression was attenuated in the presence of dominant-negative ATF3 or c-Jun. Coimmunoprecipitation and a chromatin immunoprecipitation assay revealed that ATF3 physically interacted with c-Jun and that the ATF3/c-Jun complex directly bound to the Klotho promoter through ATF3- and AP-1-binding elements. c-Jun cotransfection augmented the effects of ATF3 on Klotho transcription in vitro. Although Sirtuin 1 mRNA expression was induced by resveratrol and involved in regulating Klotho mRNA expression, it was not the primary cause for the aforementioned ATF3/c-Jun pathway. In summary, resveratrol enhances the renal expression of the anti-aging Klotho gene, and the transcriptional factors ATF3 and c-Jun functionally interact and coordinately regulate the resveratrol-mediated transcriptional activation of Klotho.

  1. Conhecimento e uso de plantas em uma comunidade caiçara do litoral sul do Estado do Rio de Janeiro, Brasil Knowledge and use of plants in a Caiçara community located on the southern coast of Rio de Janeiro State, Brazil

    Directory of Open Access Journals (Sweden)

    Rodrigo Borges

    2009-09-01

    Full Text Available A Área de Proteção Ambiental de Cairuçu (APA localiza-se no município de Paraty, RJ. É uma unidade de conservação de uso sustentável e dispõe-se a proteger o ambiente natural e as comunidades caiçaras da região. O objetivo deste estudo foi realizar um inventário etnobotânico das plantas conhecidas e utilizadas pela comunidade caiçara que habita a praia de Martim de Sá. Moram no local 30 pessoas das quais 10 foram entrevistadas. As informações etnobotânicas foram obtidas através da observação participante e entrevistas semi-estruturadas. O material botânico coletado foi depositado no Herbário do Instituto de Pesquisas Jardim Botânico do Rio de Janeiro (RB. Foram identificadas 76 espécies pertencentes a 59 gêneros e 30 famílias botânicas consideradas úteis pelos caiçaras. As três espécies mais citadas foram: Sloanea obtusifolia (Sapopema, Scherolobium denudatum (Ingá-ferro e Balizia pedicelaris (Timbuíba. Utilizou-se o Índice de Shannon (H' = 1,81 - base 10 para a análise da diversidade de espécies. O registro sobre o uso dos recursos vegetais na comunidade estudada fornece informações que podem ser utilizadas para programas de conservação baseados no conhecimento local do ambiente.The Cairuçu Environmental Protection Area (APA was created to help assure the protection of the natural environment and its sustainable use by the caiçara communities in the region. This work presents an ethnobotanical inventory of the plants known and used by the caiçara community living on Martim de Sá beach in Paraty municipality, RJ. Thirty people live in the locality and ten of them were interviewed. Ethnobotanical information was obtained through participatory observations and semi-structured interviews with the local residents. All botanical material collected was deposited in the herbarium of the Instituto de Pesquisas Jardim Botânico do Rio de Janeiro (RB. A total of 76 species belonging to 59 genera and 30

  2. Research on the Reasons of the Banishment in Daozhou of Cai Yuanding%蔡元定谪贬道州原因探析

    Institute of Scientific and Technical Information of China (English)

    顾宏义

    2016-01-01

    In the period of “Qing Yuan Dang Jin”of Southern Song Dynasty,neo-confucianist Zhu Xi was impeached and dismissed from office.In the meantime,his disciple,Cai Yuanding was imposed a heavy penalty and died in Daozhou because of demotion.On the causes of Cai�s death,many researchers believed that Cai was implicated just because of the powerful minister,Han Tuozhou�s inhibition on Zhu Xi,and he was totally innocent.But based on the scattered historical materials in the relevant peri-od especially from the letters of Zhu Xi in the contemporary period,we can find that Cai was penalized severely partly due to the political background in that period but the hidden and direct cause was be-cause of the event that Cai decided to relocate the Jianyang school to Huguosi because of the Geomantic Omen.This made the political opponents accuse Cai as an excuse and also because the event was related to Geomantic Omen,Zhu Xi and his descendants and disciples were all reluctant to reveal the truth be-hind it,which became the direct reasons of Cai�s death in Daozhou but the reasons were submerged.%南宋“庆元党禁”期间,理学家朱熹因遭劾而落职罢宫观,而其门人蔡元定却受到贬窜道州而死的重罚。对此中缘故,后世大多认定蔡元定只是因权臣韩侂胄为打击朱熹等人而受牵连,纯属“无辜被诬”。但据当时散见诸处之史料,尤其通过辨析朱熹在此前后之书信文字,可证蔡元定受此重罚,虽与当时政治大背景相关,然其直接原因,实在于蔡元定以风水之说主张迁移建阳县学至护国寺址一事,使得政敌们得以借口而窜责蔡元定。也因此重罚事牵涉风水之说,故朱熹、蔡元定及其后人、门生等道学中人皆不愿明言其间,遂使蔡元定贬窜道州之直接原因湮灭不彰。

  3. Function of c-Fos-like and c-Jun-like Proteins on Trichostatin A-induced G2/M Arrest in Physarum polycephalum

    Institute of Scientific and Technical Information of China (English)

    Xiao-Xue LI; Jun LU; Yan-Mei ZHAO; Bai-Qu HUANG

    2005-01-01

    The homologs of transcription factors c-Fos and c-Jun have been detected in slime mold Physarum polycephalum during progression of the synchronous cell cycle. Here we demonstrated that cFos-like and c-Jun-like proteins participated in G2/M transition by the regulation of the level of Cyclin B1 protein in P. polycephalum. The study of antibody neutralization revealed that interruption of the functions of c-Fos-like and c-Jun-like proteins resulted in G2/M transition arrest, implicating their functional roles in cell cycle control. When G2/M transition was blocked by histone deacetylase inhibitor trichostatin A, changes in c-Fos- and c-Jun-like protein levels, and hyperacetylation of c-Jun-like protein, were observed. The data suggest that in P. polycephalum, c-Fos- and c-Jun-like proteins may be the key factors in the regulation of histone acetylation-related G2/M transition, involving the coordinated expression and hyperacetylation of these proteins.

  4. Function of c-Fos-like and c-Jun-like proteins on trichostatin A-induced G2/M arrest in Physarum polycephalum.

    Science.gov (United States)

    Li, Xiao-Xue; Lu, Jun; Zhao, Yan-Mei; Huang, Bai-Qu

    2005-11-01

    The homologs of transcription factors c-Fos and c-Jun have been detected in slime mold Physarum polycephalum during progression of the synchronous cell cycle. Here we demonstrated that c-Fos-like and c-Jun-like proteins participated in G2/M transition by the regulation of the level of Cyclin B1 protein in P. polycephalum. The study of antibody neutralization revealed that interruption of the functions of c-Fos-like and c-Jun-like proteins resulted in G2/M transition arrest, implicating their functional roles in cell cycle control. When G2/M transition was blocked by histone deacetylase inhibitor trichostatin A, changes in c-Fos- and c-Jun-like protein levels, and hyperacetylation of c-Jun-like protein, were observed. The data suggest that in P. polycephalum, c-Fos- and c-Jun-like proteins may be the key factors in the regulation of histone acetylation-related G2/M transition, involving the coordinated expression and hyperacetylation of these proteins.

  5. Elevated cJUN expression and an ATF/CRE site within the ATF3 promoter contribute to activation of ATF3 transcription by the amino acid response.

    Science.gov (United States)

    Fu, Lingchen; Kilberg, Michael S

    2013-02-15

    Mammalian cells respond to amino acid deprivation through multiple signaling pathways referred to as the amino acid response (AAR). Transcription factors mediate the AAR after their activation by several mechanisms; examples include translational control (activating transcription factor 4, ATF4), phosphorylation (p-cJUN), and transcriptional control (ATF3). ATF4 induces ATF3 transcription through a promoter-localized C/EBP-ATF response element (CARE). The present report characterizes an ATF/CRE site upstream of the CARE that also contributes to AAR-induced ATF3 transcription. ATF4 binds to the ATF/CRE and CARE sequences and both are required for a maximal response to ATF4 induction. ATF3, which antagonizes ATF4 and represses its own gene, also exhibited binding activity to the ATF/CRE and CARE sequences. The AAR resulted in elevated total cJUN and p-cJUN protein levels and both forms exhibited binding activity to the ATF/CRE and CARE ATF3 sequences. Knockdown of AAR-enhanced cJUN expression blocked induction of the ATF3 gene and mutation of either the ATF/CRE or the CARE site prevented the cJUN-dependent increase in ATF3-driven luciferase activity. The results indicate that both increased cJUN and the cis-acting ATF/CRE sequence within the ATF3 promoter contribute to the transcriptional activation of the gene during the AAR.

  6. Puerarin reduces increased c-fos, c-jun, and type Ⅳ collagen expression caused by high glucose in glomerular mesangial cells

    Institute of Scientific and Technical Information of China (English)

    Cai-ping MAO; Zhen-lun GU

    2005-01-01

    Aim: Increased expression of c-fos, c-jun and type Ⅳ collagen (CoⅣ) in glomerular mesangial cells (GMC) are important characteristics of diabetic nephropathy.Both c-fos and c-jun regulate the gene expression of extracellular matrix components, and CoⅣ is the main component of the extracellular matrix. It has been reported that puerarin inhibits aggregation of the extracellular matrix in diabetic rats by an as yet unknown mechanism. The aim of this study is to investigate the effect of puerarin on c-fos, c-jun and CoⅣ expression in GMC cultured in medium containing 5.6 or 27.8 mmol/L glucose. Methods: The expressions ofc-fos and c-jun were measured at the protein level using flow cytometry. CoⅣ content was detected using radioimmunoassay. Protein kinase C (PKC) activity was measured using liquid scintillation counting. Results: Puerarin (10-5 mmol/L) significantly ameliorated the high-glucose effect on c-fos, c-jun and CoⅣ expression.This effect is accompanied by a reduced PKC activity in these cells. Conclusion:Our results suggest that reduced PKC activity and expression of c-fos and c-jun in GMC might participate in the mechanisms underlying the therapeutic effect of puerarin on diabetic nephropathy.

  7. Marcadores fenotípicos de atenuación en cepas de virus Junín recuperadas de individuos vacunados con la cepa Junín Candid#1

    Directory of Open Access Journals (Sweden)

    Graciela S. Gamboa

    2013-08-01

    Full Text Available La Fiebre Hemorrágica Argentina es una enfermedad producida por el virus Junín. Para la prevención de esta enfermedad se obtuvo una vacuna efectiva denominada Candid#1. Durante un ensayo clínico realizado en el INEVH, dos cepas de virus Junín fueron aisladas de sangre periférica de dos voluntarios mediante co-cultivo de células mononucleares. El objetivo de este trabajo fue comparar las características fenotípicas de atenuación de esas dos cepas recuperadas de humanos con las de la vacuna Candid#1 utilizando los indicadores de atenuación desarrollados por Contigiani y Sabattini en 1977. A tal fin se midieron los índices de letalidad, infección y protección en cobayos y ratones de diferentes edades. Las tres cepas investigadas resultaron letales para ratones recién nacidos pero no para ratones de 10 a 12 días, ratones adultos ni cobayos, aun a la más baja dilución inoculada. Los cobayos inoculados con las cepas recuperadas de humanos y con la cepa Candid#1 no presentaron síntomas de enfermedad y mostraron estar protegidos cuando fueron desafiados con una cepa patógena. Los índices de infección y de protección hallados indican que estas cepas poseen elevada capacidad infectante y protectora en las especies animales aquí estudiadas. Estos resultados demuestran que las cepas de virus Junín aisladas de voluntarios inmunizados con Candid#1 mantienen el mismo fenotipo atenuado de la vacuna Candid#1 después de un pasaje por humanos.

  8. A Benthic Invertebrate Survey of Jun Jaegyu Volcano: An active undersea volcano in Antarctic Sound, Antarctica

    Science.gov (United States)

    Quinones, G.; Brachfeld, S.; Gorring, M.; Prezant, R. S.; Domack, E.

    2005-12-01

    Jun Jaegyu volcano, an Antarctic submarine volcano, was dredged in May 2004 during cruise 04-04 of the RV Laurence M. Gould to determine rock, sediment composition and marine macroinvertebrate diversity. The objectives of this study are to examine the benthic assemblages and biodiversity present on a young volcano. The volcano is located on the continental shelf of the northeastern Antarctic Peninsula, where recent changes in surface temperature and ice shelf stability have been observed. This volcano was originally swath-mapped during cruise 01-07 of the Research Vessel-Ice Breaker Nathaniel B. Palmer. During LMG04-04 we also studied the volcano using a SCUD video camera, and performed temperature surveys along the flanks and crest. Both the video and the dredge indicate a seafloor surface heavily colonized by benthic organisms. Indications of fairly recent lava flows are given by the absence of marine life on regions of the volcano. The recovered dredge material was sieved, and a total of thirty-three invertebrates were extracted. The compilation of invertebrate community data can subsequently be compared to other benthic invertebrate studies conducted along the peninsula, which can determine the regional similarity of communities over time, their relationship to environmental change and health, if any, and their relationship to geologic processes in Antarctic Sound. Twenty-two rock samples, all slightly weathered and half bearing encrusted organisms, were also analyzed using inductively coupled plasma-optical emission spectrometry (ICP-OES). Except for one conglomerate sample, all are alkali basalts and share similar elemental compositions with fresh, unweathered samples from the volcano. Two of the encrusted basalt samples have significantly different compositions than the rest. We speculate this difference could be due to water loss during sample preparation, loss of organic carbon trapped within the vesicles of the samples and/or elemental uptake by the

  9. The leucine zipper domains of the transcription factors GCN4 and c-Jun have ribonuclease activity.

    Directory of Open Access Journals (Sweden)

    Yaroslav Nikolaev

    Full Text Available Basic-region leucine zipper (bZIP proteins are one of the largest transcription factor families that regulate a wide range of cellular functions. Owing to the stability of their coiled coil structure leucine zipper (LZ domains of bZIP factors are widely employed as dimerization motifs in protein engineering studies. In the course of one such study, the X-ray structure of the retro-version of the LZ moiety of yeast transcriptional activator GCN4 suggested that this retro-LZ may have ribonuclease activity. Here we show that not only the retro-LZ but also the authentic LZ of GCN4 has weak but distinct ribonuclease activity. The observed cleavage of RNA is unspecific, it is not suppressed by the ribonuclease A inhibitor RNasin and involves the breakage of 3',5'-phosphodiester bonds with formation of 2',3'-cyclic phosphates as the final products as demonstrated by HPLC/electrospray ionization mass spectrometry. Several mutants of the GCN4 leucine zipper are catalytically inactive, providing important negative controls and unequivocally associating the enzymatic activity with the peptide under study. The leucine zipper moiety of the human factor c-Jun as well as the entire c-Jun protein are also shown to catalyze degradation of RNA. The presented data, which was obtained in the test-tube experiments, adds GCN4 and c-Jun to the pool of proteins with multiple functions (also known as moonlighting proteins. If expressed in vivo, the endoribonuclease activity of these bZIP-containing factors may represent a direct coupling between transcription activation and controlled RNA turnover. As an additional result of this work, the retro-leucine zipper of GCN4 can be added to the list of functional retro-peptides.

  10. Alternative Polyadenylation in Triple-Negative Breast Tumors Allows NRAS and c-JUN to Bypass PUMILIO Posttranscriptional Regulation.

    Science.gov (United States)

    Miles, Wayne O; Lembo, Antonio; Volorio, Angela; Brachtel, Elena; Tian, Bin; Sgroi, Dennis; Provero, Paolo; Dyson, Nicholas

    2016-12-15

    Alternative polyadenylation (APA) is a process that changes the posttranscriptional regulation and translation potential of mRNAs via addition or deletion of 3' untranslated region (3' UTR) sequences. To identify posttranscriptional-regulatory events affected by APA in breast tumors, tumor datasets were analyzed for recurrent APA events. Motif mapping of the changed 3' UTR regions found that APA-mediated removal of Pumilio regulatory elements (PRE) was unusually common. Breast tumor subtype-specific APA profiling identified triple-negative breast tumors as having the highest levels of APA. To determine the frequency of these events, an independent cohort of triple-negative breast tumors and normal breast tissue was analyzed for APA. APA-mediated shortening of NRAS and c-JUN was seen frequently, and this correlated with changes in the expression of downstream targets. mRNA stability and luciferase assays demonstrated APA-dependent alterations in RNA and protein levels of affected candidate genes. Examination of clinical parameters of these tumors found those with APA of NRAS and c-JUN to be smaller and less proliferative, but more invasive than non-APA tumors. RT-PCR profiling identified elevated levels of polyadenylation factor CSTF3 in tumors with APA. Overexpression of CSTF3 was common in triple-negative breast cancer cell lines, and elevated CSTF3 levels were sufficient to induce APA of NRAS and c-JUN. Our results support the hypothesis that PRE-containing mRNAs are disproportionately affected by APA, primarily due to high sequence similarity in the motifs utilized by polyadenylation machinery and the PUM complex. Cancer Res; 76(24); 7231-41. ©2016 AACR.

  11. Repouso da junção neuromuscular no tratamento de crises miastênicas e colinérgicas

    Directory of Open Access Journals (Sweden)

    J. Lamartine de Assis

    1968-06-01

    Full Text Available Os autores trataram 18 crises miastênicas e colinérgicas desenvolvidas em 12 pacientes com forma generalizada e severa de miastenia grave, mediante o "repouso" da junção neuromuscular. Êste foi conseguido, em um grupo de 6 enfermos, pela suspensão das drogas anticolinesterásicas, emprego da respiração artificial e alimentação por sonda nasogástrica — "repouso relativo". Outro grupo de 6 pacientes foi submetido ao "repouso absoluto" da junção neuromuscular, mediante o uso da respiração artificial, alimentação por sonda nasogástrica e curarização prolongada pela galamina. Em mais de 50% das crises observaram-se melhoras imediatas e acentuadas com o método de tratamento pelo "repouso" da junção neuromuscular, ao lado de redução significativa da taxa de mortalidade nas crises. A evolução mostrou que os pacientes que responderam melhor durante e logo após o tratamento da crise, tiveram, também, melhor evolução ulterior. Dos 12 enfermos somente um era portador de timoma e, mesmo nesse paciente, a evolução foi satisfatória. A sensibilidade inicial ao curare foi muito grande em todos os doentes submetidos à curarização prolongada, mas, em prazo relativamente curto (alguns dias, esta hipersensibilidade diminuiu sensivelmente. Apesar de todos os cuidados, as infecções respiratórias foram a regra, exigindo tratamento enérgico e bem orientado.

  12. The sequence-specific transcription factor c-Jun targets Cockayne syndrome protein B to regulate transcription and chromatin structure.

    Directory of Open Access Journals (Sweden)

    Robert J Lake

    2014-04-01

    Full Text Available Cockayne syndrome is an inherited premature aging disease associated with numerous developmental and neurological defects, and mutations in the gene encoding the CSB protein account for the majority of Cockayne syndrome cases. Accumulating evidence suggests that CSB functions in transcription regulation, in addition to its roles in DNA repair, and those defects in this transcriptional activity might contribute to the clinical features of Cockayne syndrome. Transcription profiling studies have so far uncovered CSB-dependent effects on gene expression; however, the direct targets of CSB's transcriptional activity remain largely unknown. In this paper, we report the first comprehensive analysis of CSB genomic occupancy during replicative cell growth. We found that CSB occupancy sites display a high correlation to regions with epigenetic features of promoters and enhancers. Furthermore, we found that CSB occupancy is enriched at sites containing the TPA-response element. Consistent with this binding site preference, we show that CSB and the transcription factor c-Jun can be found in the same protein-DNA complex, suggesting that c-Jun can target CSB to specific genomic regions. In support of this notion, we observed decreased CSB occupancy of TPA-response elements when c-Jun levels were diminished. By modulating CSB abundance, we found that CSB can influence the expression of nearby genes and impact nucleosome positioning in the vicinity of its binding site. These results indicate that CSB can be targeted to specific genomic loci by sequence-specific transcription factors to regulate transcription and local chromatin structure. Additionally, comparison of CSB occupancy sites with the MSigDB Pathways database suggests that CSB might function in peroxisome proliferation, EGF receptor transactivation, G protein signaling and NF-κB activation, shedding new light on the possible causes and mechanisms of Cockayne syndrome.

  13. Alternative Polyadenylation in Triple-Negative Breast Tumors Allows NRAS and c-JUN to Bypass PUMILIO Posttranscriptional Regulation

    Science.gov (United States)

    Miles, Wayne O.; Lembo, Antonio; Volorio, Angela; Brachtel, Elena; Tian, Bin; Sgroi, Dennis; Provero, Paolo; Dyson, Nicholas

    2017-01-01

    Alternative polyadenylation (APA) is a process that changes the posttranscriptional regulation and translation potential of mRNAs via addition or deletion of 3′ untranslated region (3′ UTR) sequences. To identify posttranscriptional-regulatory events affected by APA in breast tumors, tumor datasets were analyzed for recurrent APA events. Motif mapping of the changed 3′ UTR regions found that APA-mediated removal of Pumilio regulatory elements (PRE) was unusually common. Breast tumor subtype–specific APA profiling identified triple-negative breast tumors as having the highest levels of APA. To determine the frequency of these events, an independent cohort of triple-negative breast tumors and normal breast tissue was analyzed for APA. APA-mediated shortening of NRAS and c-JUN was seen frequently, and this correlated with changes in the expression of downstream targets. mRNA stability and luciferase assays demonstrated APA-dependent alterations in RNA and protein levels of affected candidate genes. Examination of clinical parameters of these tumors found those with APA of NRAS and c-JUN to be smaller and less proliferative, but more invasive than non-APA tumors. RT-PCR profiling identified elevated levels of polyadenylation factor CSTF3 in tumors with APA. Overexpression of CSTF3 was common in triple-negative breast cancer cell lines, and elevated CSTF3 levels were sufficient to induce APA of NRAS and c-JUN. Our results support the hypothesis that PRE-containing mRNAs are disproportionately affected by APA, primarily due to high sequence similarity in the motifs utilized by polyadenylation machinery and the PUM complex. PMID:27758885

  14. Co-induction of c-fos and junB during the latent period preceding commitment of Friend erythroleukemia cells to differentiation.

    Science.gov (United States)

    Francastel, C; Mazouzi, Z; Robert-Lézénès, J

    1992-09-01

    Chemically induced differentiation of Friend murine erythroleukemia cells (F-MELC) is a multistep process with a latent period of about 12 h preceding irreversible commitment to terminal maturation. To gain understanding of the early genetic response of F-MELC to the dimethyl sulfoxide (DMSO) inducer of F-MELC differentiation, we have investigated by Northern blot analysis the expression of fos and jun family genes that encode components of the transcription factor AP-1 complex. Our results show that c-jun mRNA is not detected at any time in untreated and DMSO-treated F-MELC. In contrast, DMSO-induced differentiation of F-MELC is associated with an early and transient induction of c-fos and junB mRNAs by 2 to 8 h treatment while in presence of dexamethasone, an inhibitor of F-MELC commitment, c-fos mRNA is not detected and junB mRNA remains at basal levels. junD mRNA is detected at low levels in untreated F-MELC and remains unchanged during DMSO treatment. Furthermore, DMSO treatment in a F-MELC cell line resistant to DMSO-differentiation does not result in an early induction of c-fos and junB mRNAs. Taken together, these results indicate that the DMSO-induced F-MELC differentiation is accompanied by an early co-induction of c-fos and junB during the latent period preceding the commitment to erythroid maturation.

  15. Induced ATF-2 represses CDK4 transcription through dimerization with JunD inhibiting intestinal epithelial cell growth after polyamine depletion.

    Science.gov (United States)

    Xiao, Lan; Rao, Jaladanki N; Zou, Tongtong; Liu, Lan; Yu, Ting-Xi; Zhu, Xiao-Yu; Donahue, James M; Wang, Jian-Ying

    2010-05-01

    Intestinal epithelium is a rapidly self-renewing tissue in the body, and its homeostasis is tightly regulated by numerous factors including polyamines. Decreased levels of cellular polyamines increase activating transcription factor (ATF)-2, but the exact role and mechanism of induced ATF-2 in the regulation of intestinal epithelial cell (IEC) growth remain elusive. Cyclin-dependent kinase (CDK) 4 is necessary for the G1-to-S phase transition during the cell cycle, and its expression is predominantly controlled at the transcription level. Here, we reported that induced ATF-2 following polyamine depletion repressed CDK4 gene transcription in IECs by increasing formation of the ATF-2/JunD heterodimers. ATF-2 formed complexes with JunD as measured by immunoprecipitation using the ATF-2 and JunD antibodies and by glutathione S-transferase (GST) pull-down assays using GST-ATF-2 fusion proteins. Studies using various mutants of GST-ATF-2 revealed that formation of the ATF-2/JunD dimers depended on the COOH-terminal basic region-leucine zipper domain of ATF-2. Polyamine depletion increased ATF-2/JunD complex and inhibited CDK4 transcription as indicated by a decrease in the levels of CDK4-promoter activity and its mRNA. ATF-2 silencing not only prevented inhibition of CDK4 transcription in polyamine-deficient cells but also abolished repression of CDK4 expression induced by ectopic JunD overexpression. ATF-2 silencing also promoted IEC growth in polyamine-depleted cells. These results indicate that induced ATF-2/JunD association following polyamine depletion represses CDK4 transcription, thus contributing to the inhibition of IEC growth.

  16. Nueva especie de Mediorhynchus (Acanthocephala, Gigantorhynchidae en Turdus chiguanco (Turdidae de Junín, Perú

    Directory of Open Access Journals (Sweden)

    Rocío Moya

    2012-02-01

    Full Text Available Se describe una nueva especie de Mediorhynchus (Acanthocephala, Gigantorhynchidae basada en 36 especímenes colectados de 4 individuos de Turdus chiguanco (Lafresnaye & D’Orbigny, 1837. Las aves fueron capturadas en el distrito de Muqui, provincia de Jauja, Junín, Perú. La nueva especie, Mediorhynchus peruensis se caracteriza por la armadura de la probóscide y la longitud de los lemniscos que se extienden hasta la parte media o posterior del testículo anterior en el macho y hasta la parte media anterior del cuerpo en la hembra.

  17. Heme oxygenase-1 suppresses the apoptosis of acute myeloid leukemia cells via the JNK/c-JUN signaling pathway.

    Science.gov (United States)

    Lin, Xiaojing; Fang, Qin; Chen, Shuya; Zhe, Nana; Chai, Qixiang; Yu, Meisheng; Zhang, Yaming; Wang, Ziming; Wang, Jishi

    2015-05-01

    There are few studies on the correlation between heme oxygenase-1 (HO-1) and acute myeloid leukemia (AML). We found that HO-1 was aberrantly overexpressed in the majority of AML patients, especially in patients with acute monocytic leukemia (M5) and leukocytosis, and inhibited the apoptosis of HL-60 and U937 cells. Moreover, silencing HO-1 prolonged the survival of xenograft mouse models. Further studies demonstrated that HO-1 suppressed the apoptosis of AML cells through activating the JNK/c-JUN signaling pathway. These data indicate a molecular role of HO-1 in inhibiting cell apoptosis, allowing it to be a potential target for treating AML.

  18. Activation of c-Jun-N-terminal kinase and decline of mitochondrial pyruvate dehydrogenase activity during brain aging.

    Science.gov (United States)

    Zhou, Qiongqiong; Lam, Philip Y; Han, Derick; Cadenas, Enrique

    2009-04-02

    Mitochondrial dysfunction is often associated with aging and neurodegeneration. c-Jun-N-terminal kinase (JNK) phosphorylation and its translocation to mitochondria increased as a function of age in rat brain. This was associated with a decrease of pyruvate dehydrogenase (PDH) activity upon phosphorylation of the E(1alpha) subunit of PDH. Phosphorylation of PDH is likely mediated by PDH kinase, the protein levels and activity of which increased with age. ATP levels were diminished, whereas lactic acid levels increased, thus indicating a shift toward anaerobic glycolysis. The energy transduction deficit due to impairment of PDH activity during aging may be associated with JNK signaling.

  19. Morfologia e sedimentologia da plataforma continental brasileira adjacente a São Bento do Norte e Caiçara do Norte-RN/NE-Brasil

    OpenAIRE

    Tabosa, Werner Farkatt

    2006-01-01

    Esta dissertação apresenta os resultados de uma pesquisa desenvolvida na região de São Bento do Norte e Caiçara do Norte, litoral setentrional do Estado do Rio Grande do Norte, durante o período de Junho de 2000 a Agosto de 2001, no âmbito dos projetos MAMBMARÉ (CNPq/CTPETRO) e PROBRAL (CAPES/DAAD). O objetivo principal da pesquisa foi a caracterização da dinâmica sedimentar do litoral em questão, com base em dados relativos à dinâmica costeira (ventos, correntes, ondas e marés), levantamento...

  20. Secondary structure prediction by GLCM of CAI%元胞自动机图的蛋白质二级结构类型预测

    Institute of Scientific and Technical Information of China (English)

    胡鸿豪; 宋丽平; 肖绚

    2010-01-01

    蛋白质结构预测是后基因组时代的一项重要任务,蛋白质二级结构预测是蛋白质结构预测的关键步骤.利用氨基酸数字编码模型生成蛋白质序列的元胞自动机图(Cellular Automata Image,CAI),提出了一种基于灰度共生矩阵(Gray Level Co-occurrence Matrix,GLCM)提取纹理图像特征的方法.用扩大的协方差算法进行预测,仿真结果显示有较好的分类效果,Jackknife检验的预测成功率达到94.61%.

  1. Design and Implement Method of Discrete Mathematics CAI Teaching Component%离散数学CAI课件的设计和实现方法

    Institute of Scientific and Technical Information of China (English)

    闫浮; 岳利明

    2001-01-01

    离散数学虽然是计算机专业课的基础课程,但是抽象难懂,为了加强大家对这门课程的理解,本文作者开发了离散数学的辅助教学软件。在这篇文章中主要从离散数学教学软件的课件层次结构出发讨论辅助教学软件的自适应性。%Discrete mathematics is a basic course in computer teaching purpose, yet it is abstract and difficult to be understood. The discrete mathematics CAI software is developed to help the more comprehension on this course. The article mainly discusses the software self-adapting performance from the view of hierarchical structure of the teaching component.

  2. The Design of multimedia CAI System with Delphi%基于Delphi语言的多媒体CAI系统设计

    Institute of Scientific and Technical Information of China (English)

    林雪明

    2000-01-01

    Hypermedia support and processing is necessary in the development of CAI systems.A hyper multimedia class TAnimatecell is defined with Delphi VCL, and the fechniques ofderioing sub-multimedia class and seripts interpreter are discussed.%用Delphi语言制作计算机辅助教学软件时,必须实现对超媒体的支持与处理,针对这种情况,阐述了采用Delphi中的VCL构造TAnimateCell类的方法以及在此基础上设计多媒体类和脚本解释析器的技术.

  3. 试析Action Script下的电子技术实验CAI制作%Analysis of electronic technology experiment CAI under Action Script

    Institute of Scientific and Technical Information of China (English)

    赵莎莎

    2012-01-01

    Action Script 是一种动作脚本编程语言,用这种脚本语言编写出来的程序具有交互性强、教据处理能力强的特点,这就使得用户能够方便且容易懂得用Action Script所呈现出来的内容.鉴于动作脚本语言这样的优点,常在计算机辅助教学(CAI)中使用Action Script,尤其是在电子技术试验CAI制作方面.本文将就如何在电子技术实验计算机辅助教学制作方面运用Action Script提出一些建议.

  4. Regulation of hemeoxygenase-1 gene expression by Nrf2 and c-Jun in tertiary butylhydroquinone-stimulated rat primary astrocytes

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jin-Sun; Kim, Hee-Sun, E-mail: hskimp@ewha.ac.kr

    2014-05-16

    Highlights: • tBHQ increased HO-1 mRNA and protein levels in rat primary astrocytes. • tBHQ enhanced HO-1 gene transcription in an ARE-dependent manner. • tBHQ increased the nuclear translocation and DNA binding of Nrf2 and c-Jun to ARE. • Nrf2 and c-Jun are involved in the differential modulation of HO-1 expression. • Nrf2 and c-Jun regulate HO-1 expression via their coordinated interaction. - Abstract: Hemeoxygenase-1 (HO-1) is a phase II antioxidant enzyme that is primarily involved in detoxification and cytoprotection in a variety of tissues. However, the mechanism underlying HO-1 gene expression remains unclear. In the present study, we investigated the regulation of HO-1 expression in primary cultured astrocytes by using the natural antioxidant compound tertiary butylhydroquinone (tBHQ). We found that tBHQ increased HO-1 mRNA and protein levels. Promoter analysis revealed that tBHQ enhanced HO-1 gene transcription in an antioxidant response element (ARE)-dependent manner. In addition, tBHQ increased the nuclear translocation and DNA binding of Nrf2 and c-Jun to ARE. Small interfering RNA (siRNA) experiments demonstrated that Nrf2 and c-Jun are involved in the differential modulation of HO-1 expression. Thus, Nrf2 knockdown reduced the basal level of HO-1 expression but did not affect the fold induction by tBHQ. On the other hand, knockdown of c-Jun diminished tBHQ-mediated induction of HO-1 without affecting basal expression. The data suggest that Nrf2 generally modulates the basal expression of HO-1, while c-Jun mediates HO-1 induction in response to tBHQ. The results of co-immunoprecipitation assays demonstrated a physical interaction between Nrf2 and c-Jun in tBHQ-treated astrocytes. The results suggest that Nrf2 and c-Jun regulate HO-1 expression via their coordinated interaction in tBHQ-treated rat primary astrocytes.

  5. Role of TGF-β-induced Claudin-4 expression through c-Jun signaling in non-small cell lung cancer.

    Science.gov (United States)

    Rachakonda, Girish; Vu, Trung; Jin, Lin; Samanta, Debangshu; Datta, Pran K

    2016-10-01

    Claudin-4 has been identified as an integral member of tight junctions and has been found to be upregulated in various types of cancers especially in metastatic cancers. However, the molecular mechanism of the upregulation of Claudin-4 and its role in lung tumorigenesis are unknown. The aim of the present study is to investigate the role of Claudin-4 on migration and tumorigenicity of lung cancer cells and to examine the regulatory effects of TGF-β on Claudin-4 expression. We have observed that TGF-β induces the expression of Claudin-4 dramatically in lung cell lines in a time dependent manner. TGF-β-induced Smad signaling is important for enhancing Claudin-4 mRNA level through inducing its promoter activity. Treatment with curcumin, a c-Jun inhibitor, or stable knockdown of c-Jun abrogates TGF-β-induced Claudin-4 expression suggesting an involvement of the c-Jun pathway. Notably, TGF-β-induced Claudin-4 expression through c-Jun pathway plays a role in TGF-β-mediated motility and tumorigenicity of these cells. In support of these observations, we have uncovered that Claudin-4 is upregulated in 14 of 24 (58%) lung tumors when compared with normal lung tissue. This is the first study to show how TGF-β regulates the expression of Claudin-4 through c-Jun signaling and how this pathway contributes to the migratory and tumorigenic phenotype of lung tumor cells.

  6. Tristetraprolin induces cell cycle arrest in breast tumor cells through targeting AP-1/c-Jun and NF-κB pathway.

    Science.gov (United States)

    Xu, Li; Ning, Huan; Gu, Ling; Wang, Qinghong; Lu, Wenbao; Peng, Hui; Cui, Weiguang; Ying, Baoling; Ross, Christina R; Wilson, Gerald M; Wei, Lin; Wold, William S M; Liu, Jianguo

    2015-12-08

    The main characteristic of cancers, including breast cancer, is the ability of cancer cells to proliferate uncontrollably. However, the underlying mechanisms of cancer cell proliferation, especially those regulated by the RNA binding protein tristetraprolin (TTP), are not completely understood. In this study, we found that TTP inhibits cell proliferation in vitro and suppresses tumor growth in vivo through inducing cell cycle arrest at the S phase. Our studies demonstrate that TTP inhibits c-Jun expression through the C-terminal Zn finger and therefore increases Wee1 expression, a regulatory molecule which controls cell cycle transition from the S to the G2 phase. In contrast to the well-known function of TTP in regulating mRNA stability, TTP inhibits c-Jun expression at the level of transcription by selectively blocking NF-κB p65 nuclear translocation. Reconstitution of NF-κB p65 completely abolishes the inhibition of c-Jun transcription by TTP. Moreover, reconstitution of c-Jun in TTP-expressing breast tumor cells diminishes Wee1 overexpression and promotes cell proliferation. Our results indicate that TTP suppresses c-Jun expression that results in Wee1 induction which causes cell cycle arrest at the S phase and inhibition of cell proliferation. Our study provides a new pathway for TTP function as a tumor suppressor which could be targeted in tumor treatment.

  7. Voxel-based analysis of the immediate early gene, c-jun, in the honey bee brain after a sucrose stimulus.

    Science.gov (United States)

    McNeill, M S; Robinson, G E

    2015-06-01

    Immediate early genes (IEGs) have served as useful markers of brain neuronal activity in mammals, and more recently in insects. The mammalian canonical IEG, c-jun, is part of regulatory pathways conserved in insects and has been shown to be responsive to alarm pheromone in honey bees. We tested whether c-jun was responsive in honey bees to another behaviourally relevant stimulus, sucrose, in order to further identify the brain regions involved in sucrose processing. To identify responsive regions, we developed a new method of voxel-based analysis of c-jun mRNA expression. We found that c-jun is expressed in somata throughout the brain. It was rapidly induced in response to sucrose stimuli, and it responded in somata near the antennal and mechanosensory motor centre, mushroom body calices and lateral protocerebrum, which are known to be involved in sucrose processing. c-jun also responded to sucrose in somata near the lateral suboesophageal ganglion, dorsal optic lobe, ventral optic lobe and dorsal posterior protocerebrum, which had not been previously identified by other methods. These results demonstrate the utility of voxel-based analysis of mRNA expression in the insect brain.

  8. A feedback inhibition between miRNA-127 and TGFβ/c-Jun cascade in HCC cell migration via MMP13.

    Directory of Open Access Journals (Sweden)

    Zhihong Yang

    Full Text Available Hepatocellular carcinoma (HCC is the fifth most common cancer worldwide and is increasing in frequency in the U.S. The major reason for the low postoperative survival rate of HCC is widespread intrahepatic metastasis or invasion, and activation of TGFβ signaling is associated with the invasive phenotype. This study aims at determining the novel function of miR-127 in modulating HCC migration. Overexpression of miR-127 inhibits HCC cell migration, invasion and tumor growth in nude mice. MiR-127 directly represses matrix metalloproteinase 13 (MMP13 3'UTR activity and protein expression, and diminishes MMP13/TGFβ-induced HCC migration. In turn, TGFβ decreases miR-127 expression by enhancing c-Jun-mediated inhibition of miR-127 promoter activity. In contrast, p53 transactivates miR-127 promoter and induces miR-127 expression, which is antagonized by c-Jun. The inhibition of miR-127 by c-Jun is through TGFβ-mediated ERK and JNK pathways. The lower miR-127 expression shows a negative correlation with the higher MMP13 expression in a subset of human HCC specimens. This is the first report elucidating a feedback regulation between miR-127 and the TGFβ/c-Jun cascade in HCC migration via MMP13 that involves a crosstalk between the oncogene c-Jun and tumor suppressor p53.

  9. Cell-type-selective induction of c-jun by TAF4b directs ovarian-specific transcription networks.

    Science.gov (United States)

    Geles, Kenneth G; Freiman, Richard N; Liu, Wei-Li; Zheng, Shuang; Voronina, Ekaterina; Tjian, Robert

    2006-02-21

    Cell-type-selective expression of the TFIID subunit TAF(II)105 (renamed TAF4b) in the ovary is essential for proper follicle development. Although a multitude of signaling pathways required for folliculogenesis have been identified, downstream transcriptional integrators of these signals remain largely unknown. Here, we show that TAF4b controls the granulosa-cell-specific expression of the proto-oncogene c-jun, and together they regulate transcription of ovary-selective promoters. Instead of using cell-type-specific activators, our findings suggest that the coactivator TAF4b regulates the expression of tissue-specific genes, at least in part, through the cell-type-specific induction of c-jun, a ubiquitous activator. Importantly, the loss of TAF4b in ovarian granulosa cells disrupts cellular morphologies and interactions during follicle growth that likely contribute to the infertility observed in TAF4b-null female mice. These data highlight a mechanism for potentiating tissue-selective functions of the basal transcription machinery and reveal intricate networks of gene expression that orchestrate ovarian-specific functions and cell morphology.

  10. Pathogenic Cx31 is un/misfolded to cause skin abnormality via a Fos/JunB-mediated mechanism.

    Science.gov (United States)

    Tang, Chengyuan; Chen, Xiang; Chi, Jingwei; Yang, Dawei; Liu, Shu; Liu, Mujun; Pan, Qian; Fan, Jianbing; Wang, Danling; Zhang, Zhuohua

    2015-11-01

    Mutations in connexin-31 (Cx31) are associated with multiple human diseases, including familial erythrokeratodermia variabilis (EKV). The pathogenic mechanism of EKV-associated Cx31 mutants remains largely elusive. Here, we show that EKV-pathogenic Cx31 mutants are un/misfolded and temperature sensitive. In Drosophila, expression of pathogenic Cx31, but not wild-type Cx31, causes depigmentation and degeneration of ommatidia that are rescued by expression of either dBip or dHsp70. Ectopic expression of Cx31 in mouse skin results in skin abnormalities resembling human EKV. The affected tissues show remarkable disrupted gap junction formation and significant upregulation of chaperones Bip and Hsp70 as well as AP-1 proteins c-Fos and JunB, in addition to molecular signatures of skin diseases. Consistently, c-Fos, JunB, Bip and Hsp70 are strikingly higher in keratinocytes of EKV patients than their matched control individuals. Furthermore, a druggable AP-1 inhibitory small molecule suppresses skin phenotype and pathological abnormalities of transgenic Cx31 mice. The study suggests that Cx31 mutant proteins are un/misfolded to cause EKV likely via an AP-1-mediated mechanism and identifies a small molecule with therapeutic potential of the disease.

  11. The tight junction protein ZO-2 associates with Jun, Fos and C/EBP transcription factors in epithelial cells.

    Science.gov (United States)

    Betanzos, Abigail; Huerta, Miriam; Lopez-Bayghen, Esther; Azuara, Elisa; Amerena, José; González-Mariscal, Lorenza

    2004-01-01

    ZO-2 is a membrane-associated guanylate kinase (MAGUK) protein present at the tight junction (TJ) of epithelial cells. While confluent monolayers have ZO-2 at their cellular borders, sparse cultures conspicuously show ZO-2 at the nuclei. To study the role of nuclear ZO-2, we tested by pull-down assays and gel shift analysis the interaction between ZO-2 GST fusion proteins and different transcription factors. We identified the existence of a specific interaction of ZO-2 with Fos, Jun and C/EBP (CCAAT/enhancer binding protein). To analyze if this association is present "in vivo", we performed immunoprecipitation and immunolocalization experiments, which revealed an interaction of ZO-2 with Jun, Fos and C/EBP not only at the nucleus but also at the TJ region. To test if the association of ZO-2 with AP-1 (activator protein-1) modulates gene transcription, we performed reporter gene assays employing chloramphenicol acetyltransferase (CAT) constructs with promoters under the control of AP-1 sites. We observed that the co-transfected ZO-2 down-regulates CAT expression in a dose-dependent manner. Since ZO-2 is a multidomain protein, we proceeded to determine which region of the molecule is responsible for the modulation of gene expression, and observed that both the amino and the carboxyl domains are capable of inhibiting gene transcription.

  12. Scorpion Venom Heat-Resistant Peptide Attenuates Glial Fibrillary Acidic Protein Expression via c-Jun/AP-1.

    Science.gov (United States)

    Cao, Zhen; Wu, Xue-Fei; Peng, Yan; Zhang, Rui; Li, Na; Yang, Jin-Yi; Zhang, Shu-Qin; Zhang, Wan-Qin; Zhao, Jie; Li, Shao

    2015-11-01

    Scorpion venom has been used in the Orient to treat central nervous system diseases for many years, and the protein/peptide toxins in Buthus martensii Karsch (BmK) venom are believed to be the effective components. Scorpion venom heat-resistant peptide (SVHRP) is an active component of the scorpion venom extracted from BmK. In a previous study, we found that SVHRP could inhibit the formation of a glial scar, which is characterized by enhanced glial fibrillary acidic protein (GFAP) expression, in the epileptic hippocampus. However, the cellular and molecular mechanisms underlying this process remain to be clarified. The results of the present study indicate that endogenous GFAP expression in primary rat astrocytes was attenuated by SVHRP. We further demonstrate that the suppression of GFAP was primarily mediated by inhibiting both c-Jun expression and its binding with AP-1 DNA binding site and other factors at the GFAP promoter. These results support that SVHRP contributes to reducing GFAP at least in part by decreasing the activity of the transcription factor AP-1. In conclusion, the effects of SVHRP on astrocytes with respect to the c-Jun/AP-1 signaling pathway in vitro provide a practical basis for studying astrocyte activation and inhibition and a scientific basis for further studies of traditional medicine.

  13. Induction of c-fos and c-jun protooncogenes expression by formaldehyde-releasing and epoxy resin-based root-canal sealers in human osteoblastic cells.

    Science.gov (United States)

    Huang, Fu-Mei; Hsieh, Yih-Shou; Tai, Kuo-Wei; Chou, Ming-Yung; Chang, Yu-Chao

    2002-03-01

    An important requirement for a root-canal sealer is biologic compatibility; most evaluations have focused on general toxicological and local tissue irritating properties. There is only scant information about mutagenicity or carcinogenicity testing for root-canal sealer. It has been shown that c-fos and c-jun are induced rapidly by a variety of chemical and physical stimuli. Numerous works have extensively investigated the induction mechanisms of c-fos and c-jun protooncogenes by these agents; however, little is known about the induction of cellular signaling events and specific gene expression after cell exposure to root-canal sealers. Therefore, we used osteoblastic cell line U2-OS to examine the effect of zinc-oxide eugenol-based (N2 and Endomethasome), epoxy resin-based (AH Plus), and calcium hydroxide-based (Sealapex) root-canal sealers on the expression of c-fos and c-jun protooncogenes to understand in more detail the molecular mechanisms of root-canal sealer-induced genotoxicity. The cytotoxicity decreased in an order of N2 > Endomethasome > AH Plus > Sealapex. In addition, N2, Endomethasome, and AH Plus rapidly induced c-jun and c-fos mRNA levels in cells. However, Sealapex did not induce c-jun and c-fos mRNA expression at detectable levels all time points. Taken together, persistent induction of c-jun and c-fos protooncogenes by formaldehyde-releasing and epoxy resin-based root-canal sealers may be distributed systemically via apex to cause some unexpected adverse effects on human beings. These data should be taken into consideration when choosing a root-canal sealer.

  14. NPM-ALK oncogenic kinase promotes cell-cycle progression through activation of JNK/cJun signaling in anaplastic large-cell lymphoma.

    Science.gov (United States)

    Leventaki, Vasiliki; Drakos, Elias; Medeiros, L Jeffrey; Lim, Megan S; Elenitoba-Johnson, Kojo S; Claret, Francois X; Rassidakis, George Z

    2007-09-01

    Anaplastic large-cell lymphoma (ALCL) frequently carries the t(2;5)(p23;q35), resulting in aberrant expression of nucleophosmin-anaplastic lymphoma kinase (NPM-ALK). We show that in 293T and Jurkat cells, forced expression of active NPM-ALK, but not kinase-dead mutant NPM-ALK (210K>R), induced JNK and cJun phosphorylation, and this was linked to a dramatic increase in AP-1 transcriptional activity. Conversely, inhibition of ALK activity in NPM-ALK(+) ALCL cells resulted in a concentration-dependent dephosphorylation of JNK and cJun and decreased AP-1 DNA-binding. In addition, JNK physically binds NPM-ALK and is highly activated in cultured and primary NPM-ALK(+) ALCL cells. cJun phosphorylation in NPM-ALK(+) ALCL cells is mediated by JNKs, as shown by selective knocking down of JNK1 and JNK2 genes using siRNA. Inhibition of JNK activity using SP600125 decreased cJun phosphorylation and AP-1 transcriptional activity and this was associated with decreased cell proliferation and G2/M cell-cycle arrest in a dose-dependent manner. Silencing of the cJun gene by siRNA led to a decreased S-phase cell-cycle fraction associated with upregulation of p21 and downregulation of cyclin D3 and cyclin A. Taken together, these findings reveal a novel function of NPM-ALK, phosphorylation and activation of JNK and cJun, which may contribute to uncontrolled cell-cycle progression and oncogenesis.

  15. The role of bioactive nanofibers in enamel regeneration mediated through integrin signals acting upon C/EBPα and c-Jun.

    Science.gov (United States)

    Huang, Z; Newcomb, C J; Zhou, Y; Lei, Y P; Bringas, P; Stupp, S I; Snead, M L

    2013-04-01

    Enamel formation involves highly orchestrated intracellular and extracellular events; following development, the tissue is unable to regenerate, making it a challenging target for tissue engineering. We previously demonstrated the ability to trigger enamel differentiation and regeneration in the embryonic mouse incisor using a self-assembling matrix that displayed the integrin-binding epitope RGDS (Arg-Gly-Asp-Ser). To further elucidate the intracellular signaling pathways responsible for this phenomenon, we explore here the coupling response of integrin receptors to the biomaterial and subsequent downstream gene expression profiles. We demonstrate that the artificial matrix activates focal adhesion kinase (FAK) to increase phosphorylation of both c-Jun N-terminal kinase (JNK) and its downstream transcription factor c-Jun (c-Jun). Inhibition of FAK blocked activation of the identified matrix-mediated pathways, while independent inhibition of JNK nearly abolished phosphorylated-c-Jun (p-c-Jun) and attenuated the pathways identified to promote enamel regeneration. Cognate binding sites in the amelogenin promoter were identified to be transcriptionally up-regulated in response to p-c-Jun. Furthermore, the artificial matrix induced gene expression as evidenced by an increased abundance of amelogenin, the main protein expressed during enamel formation, and the CCAAT enhancer binding protein alpha (C/EBPα), which is the known activator of amelogenin expression. Elucidating these cues not only provides guidelines for the design of synthetic regenerative strategies and opportunities to manipulate pathways to regulate enamel regeneration, but can provide insight into the molecular mechanisms involved in tissue formation. Copyright © 2013 Elsevier Ltd. All rights reserved.

  16. Activation of c—Jun and suppression of phospho—p44/42 were involved in diphenylhydantoin—induced apoptosis of cultured rat cerebellar granule neurons

    Institute of Scientific and Technical Information of China (English)

    ZHAOLing-Zhi; SUXing-Wen; HUANGYi-Jun; QIUPeng-Xin; YANGGuang-Mei

    2003-01-01

    AIM:To investigate possible intracellular signal molecules involved in diphenylhydantoin (DPH)-mediated apoptosis of cerebellar granule neurons (CGN) and explore possible nolecular mechanisms of neurotoxicity of DPH.METHODS: Fluorescein diacetate (FDA) stain, hochest 33258 stain, and agar gel electrophoresis were used to test morphological and biological characters of primary CGN and cortical neurons (CN) in the presence or absence of 100μmol/L DPH; Western blot and RT-PCR were employed to further investigate apoptotic/survival signal moleculars involved in the neuronal apoptotic signal transdution. RESULTS:DPH 100μmol/L induced a typical apoptosis of CGN but had no toxicity on CN. Cerebellar granule neural apoptosis induced by 100μmol/L DPH was significantly inhibited by pre-treatment with SB203580(10μmol/L) or CEP-11004(1μmol/L) for 1h. DPH markedly upregulated the levels of phospho-c-Jun (active c-Jun), total c-Jun protein and c-jun mRNA in CGN. The levels of phospho-c-Jun dramatically elevated by DPH at 8 h were significantly inhibited by SB203580(10μmol/L) or CEP-11004 (1μmol/L). Moreover, the activities of p44/42 (ERK1/ERK2), other members of MAP kinases and generally believed to be important survival effetors in CGN, were markedly suppressed. However, the activities of both JNK and p38 were little affected in the process of apoptosis of CGN induced by 100μmol/L DPH. CONCLUSION: The selective toxicity of DPH on CGN is likely due to its ability to induce apoptosis of CGN, it is a process involved activation of c-Jun and suppression of the activity of p44/42.

  17. Pregnane and Xenobiotic Receptor gene expression in liver cells is modulated by Ets-1 in synchrony with transcription factors Pax5, LEF-1 and c-jun

    Energy Technology Data Exchange (ETDEWEB)

    Kumari, Sangeeta; Saradhi, Mallampati; Rana, Manjul; Chatterjee, Swagata [Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi 110067 (India); Aumercier, Marc [IRI, CNRS USR 3078, Université de Lille-Nord de France, Parc CNRS de la Haute Borne, 50 Avenue de Halley, BP 70478, 59658 Villeneuve d’Ascq Cedex (France); Mukhopadhyay, Gauranga [Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi 110067 (India); Tyagi, Rakesh K., E-mail: rktyagi@yahoo.com [Special Centre for Molecular Medicine, Jawaharlal Nehru University, New Delhi 110067 (India)

    2015-01-15

    Nuclear receptor PXR is predominantly expressed in liver and intestine. Expression of PXR is observed to be dysregulated in various metabolic disorders indicating its involvement in disease development. However, information available on mechanisms of PXR self-regulation is fragmentary. The present investigation identifies some of the regulatory elements responsible for its tight regulation and low cellular expression. Here, we report that the PXR-promoter is a target for some key transcription factors like PU.1/Ets-1, Pax5, LEF-1 and c-Jun. Interestingly, we observed that PXR-promoter responsiveness to Pax5, LEF-1 and c-Jun, is considerably enhanced by Ets transcription factors (PU.1 and Ets-1). Co-transfection of cells with Ets-1, LEF-1 and c-Jun increased PXR-promoter activity by 5-fold and also induced expression of endogenous human PXR. Site-directed mutagenesis and transfection studies revealed that two Ets binding sites and two of the three LEF binding sites in the PXR-promoter are functional and have a positive effect on PXR transcription. Results suggest that expression of Ets family members, in conjunction with Pax5, LEF-1 and c-Jun, lead to coordinated up-regulation of PXR gene transcription. Insights obtained on the regulation of PXR gene have relevance in offering important cues towards normal functioning as well as development of several metabolic disorders via PXR signaling. - Highlights: • The study identified cis-regulatory elements in the nuclear receptor PXR promoter. • Several trans-acting factors modulating the PXR-promoter have been identified. • PU.1/Ets-1, Pax5, LEF-1, c-Jun, LyF-VI and NF-1 act as modulators of the PXR-promoter. • Ets-1 in conjunction with LEF-1 and c-Jun exhibit 5-fold activation of the PXR-promoter. • Insights into PXR-regulation have relevance in normal and pathological conditions.

  18. Stimulation of T cells up-regulates expression of Ifi202, an interferon-inducible lupus susceptibility gene, through activation of JNK/c-Jun pathway

    Science.gov (United States)

    Chen, Jianming; Panchanathan, Ravichandran; Choubey, Divaker

    2008-01-01

    Studies have revealed that increased expression of interferon (IFN)-inducible Ifi202 gene (encoding p202 protein) in splenic B and T cells from B6.Nba2 congenic (congenic for Nb2 locus derived from NZB mice) female mice is associated with lupus susceptibility. However, signaling pathways that regulate Ifi202 expression in immune cells remain to be elucidated. Here we report that stimulation of T cells up-regulates the Ifi202 expression. We found that steady-state levels of Ifi202 mRNA and protein were detectable in splenic T cells from NZB mice and stimulation of T cells with anti-CD3 and anti-CD28 up-regulated expression of the Ifi202 gene. Similarly, stimulation of cells of a mouse T-cell hybridoma cell line (2B4.11) also activated transcription of the Ifi202 gene. Significantly, up-regulation of Ifi202 expression in stimulated T cells was inhibited by treatment of cells with SP600125, a specific inhibitor of c-Jun N-terminal kinase (JNK). Conversely, treatment of cells with anisomycin, a potent activator of the JNK and c-Jun, up-regulated Ifi202 expression. Consistent with the activation of JNK/c-Jun pathway by T cell stimulation, forced expression of c-Jun in 2B4 T-cells and in mouse embryonic fibroblasts (MEFs) also up-regulated the Ifi202 expression. Furthermore, we found that stimulation of T cells increased association of the activated c-Jun to the 5′-regulatory region of the Ifi202 gene in chromatin immunoprecipitation assays (ChIPs). Together, our observations demonstrate that stimulation of T cells up-regulates the Ifi202 expression in part through the JNK/c-Jun pathway. PMID:18374989

  19. CARMA1- and MyD88-dependent activation of Jun/ATF-type AP-1 complexes is a hallmark of ABC diffuse large B-cell lymphomas.

    Science.gov (United States)

    Juilland, Mélanie; Gonzalez, Montserrat; Erdmann, Tabea; Banz, Yara; Jevnikar, Zala; Hailfinger, Stephan; Tzankov, Alexandar; Grau, Michael; Lenz, Georg; Novak, Urban; Thome, Margot

    2016-04-07

    A hallmark of the diffuse large B-cell lymphoma (DLBCL) of the activated B-cell (ABC) type, a molecular subtype characterized by adverse outcome, is constitutive activation of the transcription factor nuclear factor-κB (NF-κB), which controls expression of genes promoting cellular survival and proliferation. Much less, however, is known about the role of the transcription factor activator protein-1 (AP-1) in ABC DLBCL. Here, we show that AP-1, like NF-κB, was controlled by constitutive activation of the B-cell receptor signaling component caspase recruitment domain-containing membrane-associated guanylate kinase 1 (CARMA1) and/or the Toll-like receptor signaling component myeloid differentiation primary response gene 88 (MyD88) in ABC DLBCL cell lines. In contrast to germinal center (GC) B-cell (GCB) DLBCL, ABC DLBCL cell lines expressed high levels of the AP-1 family members c-Jun, JunB, and JunD, which formed heterodimeric complexes with the AP-1 family members activating transcription factor (ATF) 2, ATF3, and ATF7. Inhibition of these complexes by a dominant-negative approach led to impaired growth of a majority of ABC DLBCL cell lines. Individual silencing of c-Jun, ATF2, or ATF3 decreased cellular survival and revealed c-Jun/ATF2-dependent control of ATF3 expression. As a consequence, ATF3 expression was much higher in ABC vs GCB DLBCL cell lines. Samples derived from DLBCL patients showed a clear trend toward high and nuclear ATF3 expression in nodal DLBCL of the non-GC or ABC subtype. These findings identify the activation of AP-1 complexes of the Jun/ATF-type as an important element controlling the growth of ABC DLBCL. © 2016 by The American Society of Hematology.

  20. Krüppel-like factor (KLF) 5 mediates cyclin D1 expression and cell proliferation via interaction with c-Jun in Ang II-induced VSMCs

    OpenAIRE

    Liu, Yu; Wen, Jin-kun; Dong, Li-Hua; Zheng, Bin; Han, Mei

    2009-01-01

    Aim: To elucidate how krüppel-like factor (KLF5) activates cyclin D1 expression in Ang II-induced vascular smooth muscle cells (VSMC) proliferation. Methods: An adenoviral vector containing the full-length cDNA of KLF5 and a recombinant plasmid expressing c-Jun were constructed. MTT assay and flow cytometric analysis were used to determine the effect of Ang II on cell growth. The luciferase assay and chromatin immunoprecipitation were used to detect the relationship between KLF5 and c-Jun in ...

  1. miR-138 protects cardiomyocytes from hypoxia-induced apoptosis via MLK3/JNK/c-jun pathway

    Energy Technology Data Exchange (ETDEWEB)

    He, Siyi; Liu, Peng; Jian, Zhao; Li, Jingwei; Zhu, Yun; Feng, Zezhou; Xiao, Yingbin, E-mail: xiaoyb@vip.sina.com

    2013-11-29

    Highlights: •First time to find miR-138 is up-regulated in hypoxic cardiomyocytes. •First time to find miR-138 targets MLK3 and regulates JNK/c-jun pathway. •Rare myocardial biopsy of patients with CHD were collected. •Both silence and overexpression of miR-138 were implemented. •Various methods were used to detect cell function. -- Abstract: Cardiomyocytes experience a series of complex endogenous regulatory mechanisms against apoptosis induced by chronic hypoxia. MicroRNAs are a class of endogenous small non-coding RNAs that regulate cellular pathophysiological processes. Recently, microRNA-138 (miR-138) has been found related to hypoxia, and beneficial for cell proliferation. Therefore, we intend to study the role of miR-138 in hypoxic cardiomyocytes and the main mechanism. Myocardial samples of patients with congenital heart disease (CHD) were collected to test miR-138 expression. Agomir or antagomir of miR-138 was transfected into H9C2 cells to investigate its effect on cell apoptosis. Higher miR-138 expression was observed in patients with cyanotic CHD, and its expression gradually increased with prolonged hypoxia time in H9C2 cells. Using MTT and LDH assays, cell growth was significantly greater in the agomir group than in the negative control (NC) group, while antagomir decreased cell survival. Dual luciferase reporter gene and Western-blot results confirmed MLK3 was a direct target of miR-138. It was found that miR-138 attenuated hypoxia-induced apoptosis using TUNEL, Hoechst staining and Annexin V-PE/7-AAD flow cytometry analysis. We further detected expression of apoptosis-related proteins. In the agomir group, the level of pro-apoptotic proteins such as cleaved-caspase-3, cleaved-PARP and Bad significantly reduced, while Bcl-2 and Bcl-2/Bax ratio increased. Opposite changes were observed in the antagomir group. Downstream targets of MLK3, JNK and c-jun, were also suppressed by miR-138. Our study demonstrates that up-regulation of miR-138 plays

  2. The selective protein kinase C inhibitor, Ro-31-8220, inhibits mitogen-activated protein kinase phosphatase-1 (MKP-1) expression, induces c-Jun expression, and activates Jun N-terminal kinase.

    Science.gov (United States)

    Beltman, J; McCormick, F; Cook, S J

    1996-10-25

    The role of protein kinase C (PKC) in inflammation, mitogenesis, and differentiation has been deduced in part through the use of a variety of PKC inhibitors. Two widely used inhibitors are the structurally related compounds GF109203X and Ro-31-8220, both of which potently inhibit PKC activity and are believed to be highly selective. While using GF109203X and Ro-31-8220 to address the role of PKC in immediate early gene expression, we observed striking differential effects by each of these two compounds. Growth factors induce the expression of the immediate early gene products MAP kinase phosphatase-1 (MKP-1), c-Fos and c-Jun. Ro-31-8220 inhibits growth factor-stimulated expression of MKP-1 and c-Fos but strongly stimulated c-Jun expression, even in the absence of growth factors. GF109203X displays none of these properties. These data suggest that Ro-31-8220 may have other pharmacological actions in addition to PKC inhibition. Indeed, Ro-31-8220 strongly stimulates the stress-activated protein kinase, JNK1. Furthermore, Ro-31-8220 apparently activates JNK in a PKC-independent manner. Neither the down-regulation of PKC by phorbol esters nor the inhibition of PKC by GF109203X affected the ability of Ro-31-8220 to activate JNK1. These data suggest that, in addition to potently inhibiting PKC, Ro-31-8220 exhibits novel pharmacological properties which are independent of its ability to inhibit PKC.

  3. Effect of Jun N-terminal kinase 1 and 2 on the replication of Penicillium marneffei in human macrophages.

    Science.gov (United States)

    Chen, Renqiong; Xi, Liyan; Huang, Xiaowen; Ma, Tuan; Ren, Hong; Ji, Guangquan

    2015-05-01

    Penicillium marneffei (P. marneffei) is a human pathogen which persists in macrophages and threatens the immunocompromised patients. To clarify the mechanisms involved, we evaluated the effect of c-Jun N-terminal kinase 1 and 2 (JNK1/2) on cytokine expression, phagosomal maturation and multiplication of P. marneffei in P. marneffei-stimulated human macrophages. P. marneffei induced the rapid phosphorylation of JNK1/2. Using the specific inhibitor of JNK1/2 (SP600125), we found that the inhibition of JNK1/2 suppressed P. marneffei-induced tumor necrosis factor-α and IL-10 production. In addition, the presence of SP600125 increased phagosomal acidification and maturation and decreased intracellular replication. These data suggest that JNK1/2 may play an important role in promoting the replication of P. marneffei. Our findings further indicate that the pathogen through the JNK1/2 pathway may attenuate the immune response and macrophage antifungal function.

  4. Rika-Shoshi, the First Physics Experiment Textbook Published in Japanese and its Editor, Jun'ichi Udagawa

    Science.gov (United States)

    Takahashi, Hiroshi; Akabane, Akira; Shozawa, Jun; Tamaki, Toyomi

    The aim of this study is to examine the teaching of physics experiment at elementary and secondary school levels at the time when Japanese science education commenced. In this report, we focused on the first Japanese textbook of physics experiment, Rika-Shoshi, published in 1882 and the editor of the book, Udagawa Jun'ichi. Many experiments in Rika-Shoshi can be performed using low-cost everyday materials. We compare Rika-Shoshi with the original English textbooks and describe Udagawa's physics teaching in the Gunma Normal School based on the documents in the Gunma University archives. We discuss how we can learn from physics education as taught about 130 years ago.

  5. Diversidad florística asociada a las lagunas andinas Pomacocha y Habascocha, Junín, Perú

    Directory of Open Access Journals (Sweden)

    Mercedes Flores

    2013-05-01

    Full Text Available Se realizó un estudio de la diversidad florística de los alrededores de las lagunas Pomacocha y Habascocha (4350 - 4550 m de altitud, 11°45’-11°48’S y 75°12’-75°15’O, Provincia de Concepción, Junín, Perú. Se han registrado 29 familias, 64 géneros y 100 especies. Poaceae fue la familia con mayor diversidad específica (25%, seguida por Asteraceae (24% y Gentianaceae (6%. Se hace una comparación de la composición florística de la puna de Concepción con la de otras localidades de la puna del Perú.

  6. MEKKs, GCKs, MLKs, PAKs, TAKs, and tpls: upstream regulators of the c-Jun amino-terminal kinases?

    Science.gov (United States)

    Fanger, G R; Gerwins, P; Widmann, C; Jarpe, M B; Johnson, G L

    1997-02-01

    Regulation of the mitogen-activated protein kinase (MAPK) family members - which include the extracellular response kinases (ERKs), p38/HOG1, and the c-Jun amino-terminal kinases (JNKs) - plays a central role in mediating the effects of diverse stimuli encompassing cytokines, hormones, growth factors and stresses such as osmotic imbalance, heat shock, inhibition of protein synthesis and irradiation. A rapidly increasing number of kinases that activate the JNK pathways has been described recently, including the MAPK/ERK kinase kinases, p21-activated kinases, germinal center kinase, mixed lineage kinases, tumor progression locus 2, and TGF-beta-activated kinase. Thus, regulation of the JNK pathway provides an interesting example of how many different stimuli can converge into regulating pathways critical for the determination of cell fate.

  7. On Mr. Cai Yuan-pei's Sports Thought and its Inspirations%论蔡元培先生的体育思想及其启示

    Institute of Scientific and Technical Information of China (English)

    杜景强

    2013-01-01

    Mr. Cai Yuan-pei is a famous educator and practitioner in Chinese modern history of education, he presented a thought of military country education from the perspective of“resisting foreign imposition and saving motherland, strengthening military and enric-hing country”;advocated the idea of“sports first in full personality”, emphasizing that physical education plays a fundamental role in the comprehensive development education; focused the popularity of sports, specially thinking that citizens should develop lifelong physical exercise regularly;advocated actively to encourages and support women's equality to participate in sports. This paper considers that the application of Cai Yuan-pei's sports ideology will be helpful for sports workers to learn from previous useful thinking and elimi-nate negative factors that probably arise in current physical education.%蔡元培先生是中国近代教育史上著名的教育家和实践家,他站在“御侮救国,强兵富国”的立场提出了军国民体育思想;提倡“完全人格,首在体育”的体育教育主张强调体育在全面发展教育中,具有基础性的重要作用;在强调体育的普及的同时,还特别强调国民应该养成经常锻炼的终身体育思想。提倡积极鼓励和大力支持妇女平等的参加体育。将蔡元培的体育思想运用到当前体育教育中,有助于广大体育工作者吸取前人有益的思维成果,消除当前体育教育工作中可能出现的不利因素。

  8. Folate receptor alpha is associated with cervical carcinogenesis and regulates cervical cancer cells growth by activating ERK1/2/c-Fos/c-Jun.

    Science.gov (United States)

    Liu, Chunliang; Ding, Ling; Bai, Lixia; Chen, Xiao; Kang, Huijie; Hou, Lifang; Wang, Jintao

    2017-09-30

    Folate receptor alpha (FRα) is over-expressed in numerous epithelial malignancies, however, the association between FRα and cervical cancer remains unclear. The purpose of this study was to explore the effects of FRα on cervical cancer and its regulation of the ERK signaling pathway. In this case-control study, moderate/strong expression of FRα, phosphorylated ERK1/2 (p-ERK1/2), p-c-Fos, and p-c-Jun proteins was increased with the progressive severity of cervix lesions (P c-Fos, and p-c-Jun proteins was positively correlated with those of FRα protein in cervical squamous cell carcinoma (SCC) group (P c-Fos, and p-c-Jun proteins. The results suggest that FRα is associated with the progression of cervical cancer and regulates cervical cancer cells growth through phosphorylating ERK1/2, c-Fos, and c-Jun, which are key factors of the ERK signaling pathway. Therefore, FRα may be an effective target for early detection and therapy of cervical cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Oxidant exposure induces cysteine-rich protein 61 (CCN1 via c-Jun/AP-1 to reduce collagen expression in human dermal fibroblasts.

    Directory of Open Access Journals (Sweden)

    Zhaoping Qin

    Full Text Available Human skin is a primary target of oxidative stress from reactive oxygen species (ROS generated from both extrinsic and intrinsic sources. Oxidative stress inhibits the production of collagen, the most abundant protein in skin, and thus contributes to connective tissue aging. Here we report that cysteine-rich protein 61 (CCN1, a negative regulator of collagen production, is markedly induced by ROS and mediates loss of type I collagen in human dermal fibroblasts. Conversely, antioxidant N-acetyl-L-cysteine significantly reduced CCN1 expression and prevented ROS-induced loss of type I collagen in both human dermal fibroblasts and human skin in vivo. ROS increased c-Jun, a critical member of transcription factor AP-1 complex, and increased c-Jun binding to the AP-1 site of the CCN1 promoter. Functional blocking of c-Jun significantly reduced CCN1 promoter and gene expression and thus prevented ROS-induced loss of type I collagen. Targeting the c-Jun/CCN1 axis may provide clinical benefit for connective tissue aging in human skin.

  10. Pregnane and Xenobiotic Receptor gene expression in liver cells is modulated by Ets-1 in synchrony with transcription factors Pax5, LEF-1 and c-Jun.

    Science.gov (United States)

    Kumari, Sangeeta; Saradhi, Mallampati; Rana, Manjul; Chatterjee, Swagata; Aumercier, Marc; Mukhopadhyay, Gauranga; Tyagi, Rakesh K

    2015-01-15

    Nuclear receptor PXR is predominantly expressed in liver and intestine. Expression of PXR is observed to be dysregulated in various metabolic disorders indicating its involvement in disease development. However, information available on mechanisms of PXR self-regulation is fragmentary. The present investigation identifies some of the regulatory elements responsible for its tight regulation and low cellular expression. Here, we report that the PXR-promoter is a target for some key transcription factors like PU.1/Ets-1, Pax5, LEF-1 and c-Jun. Interestingly, we observed that PXR-promoter responsiveness to Pax5, LEF-1 and c-Jun, is considerably enhanced by Ets transcription factors (PU.1 and Ets-1). Co-transfection of cells with Ets-1, LEF-1 and c-Jun increased PXR-promoter activity by 5-fold and also induced expression of endogenous human PXR. Site-directed mutagenesis and transfection studies revealed that two Ets binding sites and two of the three LEF binding sites in the PXR-promoter are functional and have a positive effect on PXR transcription. Results suggest that expression of Ets family members, in conjunction with Pax5, LEF-1 and c-Jun, lead to coordinated up-regulation of PXR gene transcription. Insights obtained on the regulation of PXR gene have relevance in offering important cues towards normal functioning as well as development of several metabolic disorders via PXR signaling. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Up-regulation of c-Jun inhibits proliferation and induces apoptosis via caspase-triggered c-Abl cleavage in human multiple myeloma.

    Science.gov (United States)

    Podar, Klaus; Raab, Marc S; Tonon, Giovanni; Sattler, Martin; Barilà, Daniela; Zhang, Jing; Tai, Yu-Tzu; Yasui, Hiroshi; Raje, Noopur; DePinho, Ronald A; Hideshima, Teru; Chauhan, Dharminder; Anderson, Kenneth C

    2007-02-15

    Here we show the antimyeloma cytotoxicity of adaphostin and carried out expression profiling of adaphostin-treated multiple myeloma (MM) cells to identify its molecular targets. Surprisingly, c-Jun was the most up-regulated gene even at the earliest point of analysis (2 h). We also observed adaphostin-induced c-Abl cleavage in immunoblot analysis. Proteasome inhibitor bortezomib, but not melphalan or dexamethasone, induced similar effects, indicating unique agent-dependent mechanisms. Using caspase inhibitors, as well as caspase-resistant mutants of c-Abl (TM-c-Abl and D565A-Abl), we then showed that c-Abl cleavage in MM cells requires caspase activity. Importantly, both overexpression of the c-Abl fragment or c-Jun and knockdown of c-Abl and c-Jun expression by small interfering RNA confirmed that adaphostin-induced c-Jun up-regulation triggers downstream caspase-mediated c-Abl cleavage, inhibition of MM cell growth, and induction of apoptosis. Finally, our data suggest that this mechanism may not only be restricted to MM but may also be important in a broad range of malignancies including erythroleukemia and solid tumors.

  12. NPM-ALK and the JunB transcription factor regulate the expression of cytotoxic molecules in ALK-positive, anaplastic large cell lymphoma.

    Science.gov (United States)

    Pearson, Joel D; Lee, Jason K H; Bacani, Julinor T C; Lai, Raymond; Ingham, Robert J

    2011-01-30

    Anaplastic lymphoma kinase-positive, anaplastic large cell lymphoma (ALK+ ALCL) is an aggressive non-Hodgkin lymphoma of T/null immunophenotype that is most prevalent in children and young adults. The normal cellular counterpart of this malignancy is presumed to be the cytotoxic T lymphocyte (CTL), and this presumption is partly based on the observation that these tumour cells often express cytotoxic granules containing Granzyme B (GzB) and Perforin. Chromosomal translocations involving the gene encoding for the ALK tyrosine kinase are also characteristic of ALK+ ALCL, and the resulting fusion proteins (e.g. NPM-ALK) initiate signalling events important in ALK+ ALCL pathogenesis. These events include the elevated expression of JunB; an AP-1 family transcription factor that promotes ALK+ ALCL proliferation. In this report we demonstrate that JunB is a direct transcriptional activator of GzB and that GzB transcription is also promoted by NPM-ALK. We found that Perforin expression was not regulated by JunB, but was promoted by NPM-ALK in some cell lines and inhibited by it in others. In conclusion, our study makes the novel observation that signalling through NPM-ALK and JunB affect the expression of cytotoxic molecules in ALK+ ALCL. Moreover, these findings demonstrate the expression of GzB and Perforin in this lymphoma is not solely due its presumed CTL origin, but that oncogenic signalling is actively influencing the expression of these proteins.

  13. Unfolding of bZIP dimers formed by the ATF-2 and c-Jun transcription factors is not a simple two-state transition.

    Science.gov (United States)

    Carrillo, R J; Privalov, P L

    2010-10-01

    The varied selectivity of bZIP transcription factors stems from the fact that they are dimers consisting of two not necessarily identical subunits held together by a leucine zipper dimerization domain. Determining their stability is therefore important for understanding the mechanism of formation of these transcription factors. The most widely used approach for this problem consists of observing temperature-induced dissociation of the bZIPs by any means sensitive to their structural changes, particularly optical methods. In calculating thermodynamic characteristics of this process from such data it is usually assumed that it represents a two-state transition. However, scanning micro-calorimetric study of the temperature-induced unfolding/dissociation of the three bZIPs formed by the ATF-2 and c-Jun proteins, i.e. the two homodimers (ATF-2/ATF-2) and (c-Jun/c-Jun) and the heterodimer (ATF-2/c-Jun), showed that this process does not represent a two-state transition, as found previously with the GCN4 homodimeric bZIP protein. This raises doubt about all indirect estimates of bZIP thermodynamic characteristics based on analysis of their optically-observed temperature-induced changes. 2010 Elsevier B.V. All rights reserved.

  14. Predicting Virulence of Aeromonas Isolates Based-on Changes in Transcription of c-jun and c-fos in Human Tissue Culture Cells

    Science.gov (United States)

    Aims: To assess virulence of Aeromonas isolates based on the change in regulation of c-jun and c-fos in the human intestinal tissue culture cell line Caco-2. Methods and Results: Aeromonas cells were added to Caco-2 cells at approximately a one to one ratio. After 1, 2 and 3 ...

  15. Reduced retinal microvascular density, improved forepaw reach, comparative microarray and gene set enrichment analysis with c-jun targeting DNA enzyme.

    Directory of Open Access Journals (Sweden)

    Cecilia W S Chan

    Full Text Available Retinal neovascularization is a critical component in the pathogenesis of common ocular disorders that cause blindness, and treatment options are limited. We evaluated the therapeutic effect of a DNA enzyme targeting c-jun mRNA in mice with pre-existing retinal neovascularization. A single injection of Dz13 in a lipid formulation containing N-[1-(2,3-dioleoyloxypropyl]-N,N,N-trimethylammonium methyl-sulfate and 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine inhibited c-Jun expression and reduced retinal microvascular density. The DNAzyme inhibited retinal microvascular density as effectively as VEGF-A antibodies. Comparative microarray and gene expression analysis determined that Dz13 suppressed not only c-jun but a range of growth factors and matrix-degrading enzymes. Dz13 in this formulation inhibited microvascular endothelial cell proliferation, migration and tubule formation in vitro. Moreover, animals treated with Dz13 sensed the top of the cage in a modified forepaw reach model, unlike mice given a DNAzyme with scrambled RNA-binding arms that did not affect c-Jun expression. These findings demonstrate reduction of microvascular density and improvement in forepaw reach in mice administered catalytic DNA.

  16. Crystal Structure of Jun a 1, the Major Cedar Pollen Allergen from Juniperus ashei, Reveals a Parallel β-Helical Core*

    Science.gov (United States)

    Czerwinski, Edmund W.; Midoro-Horiuti, Terumi; White, Mark A.; Brooks, Edward G.; Goldblum, Randall M.

    2008-01-01

    Pollen from cedar and cypress trees is a major cause of seasonal hypersensitivity in humans in several regions of the Northern Hemisphere. We report the first crystal structure of a cedar allergen, Jun a 1, from the pollen of the mountain cedar Juniperus ashei (Cupressaceae). The core of the structure consists primarily of a parallel β-helix, which is nearly identical to that found in the pectin/pectate lyases from several plant pathogenic microorganisms. Four IgE epitopes mapped to the surface of the protein are accessible to the solvent. The conserved vWiDH sequence is covered by the first 30 residues of the N terminus. The potential reactive arginine, analogous to the pectin/pectate lyase reaction site, is accessible to the solvent, but the substrate binding groove is blocked by a histidine-aspartate salt bridge, a glutamine, and an α-helix, all of which are unique to Jun a 1. These observations suggest that steric hindrance in Jun a 1 precludes enzyme activity. The overall results suggest that it is the structure of Jun a 1 that makes it a potent allergen. PMID:15539389

  17. Induction of heat shock protein 70 (Hsp70 prevents neuregulin-induced demyelination by enhancing the proteasomal clearance of c-Jun

    Directory of Open Access Journals (Sweden)

    Rick T Dobrowsky

    2012-12-01

    Full Text Available Modulating molecular chaperones is emerging as an attractive approach to treat neurodegenerative diseases associated with protein aggregation, DPN (diabetic peripheral neuropathy and possibly, demyelinating neuropathies. KU-32 [N-(7-((2R,3R,4S,5R-3,4-dihydroxy-5-methoxy-6,6-dimethyl-tetrahydro-2H-pyran-2-yloxy-8-methyl-2-oxo-2H-chromen-3-ylacetamide] is a small molecule inhibitor of Hsp90 (heat shock protein 90 and reverses sensory deficits associated with myelinated fibre dysfunction in DPN. Additionally, KU-32 prevented the loss of myelinated internodes induced by treating myelinated SC (Schwann cell-DRG (dorsal root ganglia sensory neuron co-cultures with NRG1 (neuregulin-1 Type 1. Since KU-32 decreased NRG1-induced demyelination in an Hsp70-dependent manner, the goal of the current study was to clarify how Hsp70 may be mechanistically linked to preventing demyelination. The activation of p42/p44 MAPK (mitogen-activated protein kinase and induction of the transcription factor c-Jun serve as negative regulators of myelination. NRG1 activated MAPK, induced c-Jun expression and promoted a loss of myelin segments in DRG explants isolated from both WT (wild-type and Hsp70 KO (knockout mice. Although KU-32 did not block the activation of MAPK, it blocked c-Jun induction and protected against a loss of myelinated segments in WT mice. In contrast, KU-32 did not prevent the NRG1-dependent induction of c-Jun and loss of myelin segments in explants from Hsp70 KO mice. Overexpression of Hsp70 in myelinated DRG explants prepared from WT or Hsp70 KO mice was sufficient to block the induction of c-Jun and the loss of myelin segments induced by NRG1. Lastly, inhibiting the proteasome prevented KU-32 from decreasing c-Jun levels. Collectively, these data support that Hsp70 induction is sufficient to prevent NRG1-induced demyelination by enhancing the proteasomal degradation of c-Jun.

  18. Induction of heat shock protein 70 (Hsp70) prevents neuregulin-induced demyelination by enhancing the proteasomal clearance of c-Jun.

    Science.gov (United States)

    Li, Chengyuan; Ma, Jiacheng; Zhao, Huiping; Blagg, Brian S J; Dobrowsky, Rick T

    2012-12-06

    Modulating molecular chaperones is emerging as an attractive approach to treat neurodegenerative diseases associated with protein aggregation, DPN (diabetic peripheral neuropathy) and possibly, demyelinating neuropathies. KU-32 [N-(7-((2R,3R,4S,5R)-3,4-dihydroxy-5-methoxy-6,6-dimethyl-tetrahydro-2H-pyran-2-yloxy)-8-methyl-2-oxo-2H-chromen-3-yl)acetamide] is a small molecule inhibitor of Hsp90 (heat shock protein 90) and reverses sensory deficits associated with myelinated fibre dysfunction in DPN. Additionally, KU-32 prevented the loss of myelinated internodes induced by treating myelinated SC (Schwann cell)-DRG (dorsal root ganglia) sensory neuron co-cultures with NRG1 (neuregulin-1 Type 1). Since KU-32 decreased NRG1-induced demyelination in an Hsp70-dependent manner, the goal of the current study was to clarify how Hsp70 may be mechanistically linked to preventing demyelination. The activation of p42/p44 MAPK (mitogen-activated protein kinase) and induction of the transcription factor c-Jun serve as negative regulators of myelination. NRG1 activated MAPK, induced c-Jun expression and promoted a loss of myelin segments in DRG explants isolated from both WT (wild-type) and Hsp70 KO (knockout) mice. Although KU-32 did not block the activation of MAPK, it blocked c-Jun induction and protected against a loss of myelinated segments in WT mice. In contrast, KU-32 did not prevent the NRG1-dependent induction of c-Jun and loss of myelin segments in explants from Hsp70 KO mice. Overexpression of Hsp70 in myelinated DRG explants prepared from WT or Hsp70 KO mice was sufficient to block the induction of c-Jun and the loss of myelin segments induced by NRG1. Lastly, inhibiting the proteasome prevented KU-32 from decreasing c-Jun levels. Collectively, these data support that Hsp70 induction is sufficient to prevent NRG1-induced demyelination by enhancing the proteasomal degradation of c-Jun.

  19. Modelo matemático para o Problema de Alocação de Berços em portos com limitações de operação de carga ao longo do cais

    Directory of Open Access Journals (Sweden)

    Ivan Bridi Gimenes Rodrigues

    Full Text Available Resumo: A exploração de petróleo no Brasil é realizada por plataformas em alto-mar que demandam diversas cargas levadas por navios. Os portos para atender esses navios têm de manusear vários tipos de carga e, por conta dessa variedade, trechos para movimentar cada tipo de carga são determinados ao longo do cais, aumentando a complexidade do planejamento da atracação dos navios. Visando aumentar a eficiência na operação desses portos, este artigo propõe um modelo matemático para o problema de alocação de berços contínuos que difere das demais por apresentar restrições nas operações de cargas ao longo do cais. Utilizaram-se dados reais da Companhia Portuária de Vila Velha (CPVV para avaliar o modelo. Utilizou-se o CPLEX 12.6 para executar o modelo e instâncias de até 147 navios com 440 metros de cais foram resolvidas de forma ótima. Os resultados são apresentados e comparados com os alcançados pelo método manual atual, evidenciando ganhos importantes.

  20. 蔡氏声带麻痹开音汤治疗慢性声带麻痹临床观察%Clinical Observation of Cai's Vocal Cord Paralysis Kaiyin Decoction Treatment of Chronic Vocal Cord Paralysis

    Institute of Scientific and Technical Information of China (English)

    田永远; 刘宏建; 张博; 邢金燕

    2014-01-01

    Objective:To observe the clinical curative effect of Cai's Vocal Cord Paralysis Kaiyin Decoction treatment of chronic vocal cord paralysis. Methods:21 cases of chronic patients with vocal cord paralysis were treated with Cai's Vocal Cord Paralysis Kaiyin De-coction,14 days for one course of treatment,and observed the efficiency. Results:21 patients were effective in 17 cases,invalid 4 cases, efficiency of 80. 95% . Conclusion:Cai's Vocal Cord Paralysis Kaiyin Decoction in the treatment of chronic vocal cord paralysis has sat-isfactory clinical effect.%目的:观察蔡氏声带麻痹开音汤治疗慢性声带麻痹的临床疗效。方法:21例慢性声带麻痹患者均予以蔡氏声带麻痹开音汤口服,14 d 为1个疗程,观察治疗有效率。结果:21例患者中有效17例,无效4例,有效率80.95%。结论:蔡氏声带麻痹开音汤治疗慢性声带麻痹临床效果满意。

  1. Implementation and Control of Animation System for Machine Theory CAI System%机械原理实验CAI动画系统的实现与控制

    Institute of Scientific and Technical Information of China (English)

    徐建生; 夏先平; 胡家顺

    2001-01-01

    A courseware for demonstrating the animation of link mechanism used in machine theory CAI was developed under Visual Basic environment. The simulation and control of the movement were achieved. Beyonduser friendly and easy to use, the system can simulate the movement accurately and visually. The control of themovement, such as pausing, rotating clockwise or anti-clockwise, displaying the limitation position, is easy torealize at any time and any position. The size of any component can be changed and the type of the mechanismcan be selected by user and the type name of mechanism can be displayed automatically.%利用Visual Basic平台研制了连杆机构动画演示系统的CAI课件,实现了机构动画的计算机模拟运动和仿真控制。该系统界面友好,操作方便,机构运动准确形象,特别易于控制的实现,可在机构运动中任意实现暂停,正转,反转,极位显示;亦可在机构运动状态下任意实现构件尺寸的修改和机构类型的转换,并实现机构类型与机构名称的自动显示。

  2. Adaptive Hypermedia Technique and its Applications in Intelligent CAI%自适应超媒体技术及其在智能化CAI中的应用

    Institute of Scientific and Technical Information of China (English)

    周学海; 周立; 龚育昌; 赵振西

    2001-01-01

    将自适应超媒体的方法和技术应用于智能教学系统,可充分体现因材施教的思想,提高学生的学习效果。文章介绍了自适应超媒体系统的关键方法和技术,描述了智能教学系统的组成与结构,然后结合自适应教学系统KDAES的研制讨论了自适应技术对教学系统智能化的支持及系统核心模块--学生模型的构建。%Applying the technique of adaptive hypermedia to intelligent educational systems will reflect the thought of individualizing the course material to different students and thus will enhance the learning performance.This paper describes the key methods and techniques of adaptive hypermedia systems and the structure of intelligent educational systems.Then with the development of an adaptive educational system named KDAES,We discuss how adaptive techniques provide support to the intelligence of CAI and the creation of student model,which is a kernel module of system.

  3. "The Development and Application of Analytic Geometry" of CAI Software%《解析几何》CAI软件的开发与应用

    Institute of Scientific and Technical Information of China (English)

    任永宏

    2015-01-01

    《解析几何》多媒体CAI软件在页面设计、内容导航、学习自查、答疑、以及师生交互、生生交互等方面均充分利用了网络技术的特点,便于学生进行网络学习。软件有多种应用形式,可供教师在多功能教室进行群体教学,显著提高教学质量;可供个体远程上网学习、测试、评估、互动;它是一个丰富的高校师生数学学习资源库。%"Analytic geometry" multimedia CAI software in the page design, navigation, learning self-examination, Q & A, and teacher-student interaction, student student interaction and other aspects were made full use of the characteristics of network technology, to facilitate students' learning. Various forms of application software, can be used by teachers in the multi-function classroom teaching groups, significantly improve the quality of teaching; for individual remote online learning, test, evaluation, interaction; it is a rich university students mathematics learning resource repository.

  4. CAI Course Ware and the Basic Acounting Instruction Innovations%CAI课件与基础会计学教学创新

    Institute of Scientific and Technical Information of China (English)

    苏淑欢

    2002-01-01

    随着计算机技术的飞速发展,CAI(Computer Assisted Instruction)已经成为远距离教学的重要手段,成为一门新兴的研究课题.计算机硬件功能的日益增强,为设计教学课件提供了高速、大容量、低故障、通讯方便的硬件环境.具有强大功能的各种支撑软件平台,为设计高质量的CAI课件提供了理想的设计环境.借助计算机技术,可以仿真地将在课堂里单靠一块黑板一支粉笔难以描述的实际操作再现.CAI课件是会计教学手段的全新模式.本文主要阐述广州市广播电视大学组织开发的基础会计学CAI课件的设计构思和原则,以及通过这一课件的开发得出的几点启发.

  5. 蔡邕“从卓致死”本事刍议%Analysis on Cai Yong's Death as a Follower of Dong Zhuo

    Institute of Scientific and Technical Information of China (English)

    陈海燕

    2011-01-01

    Dong Zhuo led his force into the capital,starting a period of warlord chaos and political instability in late Han Dynasty.Undoubtedly,as a cruel dictator,Dong Zhuo's death does not deserve a single pity.But his grace to Cai Yong and his talent has brought%董卓带兵入京,开启了汉末政坛军阀混战、动荡不安的局面。毫无疑问,作为一介残忍暴虐的武夫,他死不足惜,但他对蔡邕的恩遇和重用,却造就了蔡邕的悲剧命运。随着对董卓之死所发出的一声叹息,蔡邕被王允斥为附逆而下狱,最终死于非命。蔡邕之死,历来论者纷纭,观点不一。本文尝试结合汉末的政治环境及蔡邕的人生经历对他所造成的影响等方面,对蔡邕"从卓被杀"的原因进行多方面的分析。

  6. SUMOylation of the inducible (c-Fos:c-Jun)/AP-1 transcription complex occurs on target promoters to limit transcriptional activation.

    Science.gov (United States)

    Tempé, D; Vives, E; Brockly, F; Brooks, H; De Rossi, S; Piechaczyk, M; Bossis, G

    2014-02-13

    The inducible proto-oncogenic (c-Fos:c-Jun)/AP-1 transcription complex binds 12-O-tetradecanoylphorbol 13-acetate (TPA)-responsive elements (TRE) in its target genes. It is tightly controlled at multiple levels to avoid the deleterious effects of its inappropriate activation. In particular, SUMOylation represses its transactivation capacity in transient reporter assays using constitutively expressed proteins. This led to the presumption that (c-Fos:c-Jun)/AP-1 SUMOylation would be required to turn-off transcription of its target genes, as proposed for various transcription factors. Instead, thanks to the generation of an antibody specific for SUMO-modified c-Fos, we provide here direct evidence that SUMOylated c-Fos is present on a stably integrated reporter TPA-inducible promoter at the onset of transcriptional activation and colocalizes with RNA polymerase II within chromatin. Interestingly, (c-Fos:c-Jun)/AP-1 SUMOylation limits reporter gene induction, as well as the appearance of active transcription-specific histone marks on its promoter. Moreover, non-SUMOylatable mutant (c-Fos:c-Jun)/AP-1 dimers accumulate to higher levels on their target promoter, suggesting that SUMOylation might facilitate the release of (c-Fos:c-Jun)/AP-1 from promoters. Finally, activation of GADD153, an AP-1 target gene, is also associated with a rapid increase in SUMOylation at the level of its TRE and c-Fos SUMOylation dampens its induction by TPA. Taken together, our data suggest that SUMOylation could serve to buffer transcriptional activation of AP-1 target genes.

  7. Immediate expression of c-fos and c-jun mRNA in a model of intestinal autotransplantation and ischemia-reperfusion in situ

    Science.gov (United States)

    Santos, Maria Mercês; Tannuri, Ana Cristina Aoun; Coelho, Maria Cecilia Mendonça; de Oliveira Gonçalves, Josiane; Serafini, Suellen; da Silva, Luiz Fernando Ferraz; Tannuri, Uenis

    2015-01-01

    OBJECTIVE: Intestinal ischemia-reperfusion injury occurs in several clinical conditions and after intestinal transplantation. The aim of the present study was to investigate the phenomena of apoptosis and cell proliferation in a previously described intestinal ischemia-reperfusion injury autograft model using immunohistochemical markers. The molecular mechanisms involved in ischemia-reperfusion injury repair were also investigated by measuring the expression of the early activation genes c-fos and c-jun, which induce apoptosis and cell proliferation. MATERIALS AND METHODS: Thirty adult male Wistar rats were subjected to surgery for a previously described ischemia-reperfusion model that preserved the small intestine, the cecum and the ascending colon. Following reperfusion, the cecum was harvested at different time points as a representative segment of the intestine. The rats were allocated to the following four subgroups according to the reperfusion time: subgroup 1: 5 min; subgroup 2: 15 min; subgroup 3: 30 min; and subgroup 4: 60 min. A control group of cecum samples was also collected. The expression of c-fos, c-jun and immunohistochemical markers of cell proliferation and apoptosis (Ki67 and TUNEL, respectively) was studied. RESULTS: The expression of both c-fos and c-jun in the cecum was increased beginning at 5 min after ischemia-reperfusion compared with the control. The expression of c-fos began to increase at 5 min, peaked at 30 min, and exhibited a declining tendency at 60 min after reperfusion. A progressive increase in c-jun expression was observed. Immunohistochemical analyses confirmed these observations. CONCLUSION: The early activation of the c-fos and c-jun genes occurred after intestinal ischemia-reperfusion injury, and these genes can act together to trigger cell proliferation and apoptosis. PMID:26039956

  8. A novel function of B-cell translocation gene 1 (BTG1) in the regulation of hepatic insulin sensitivity in mice via c-Jun.

    Science.gov (United States)

    Xiao, Fei; Deng, Jiali; Yu, Junjie; Guo, Yajie; Chen, Shanghai; Guo, Feifan

    2016-01-01

    Insulin resistance is one of the major factors contributing to metabolic diseases, but the underlying mechanisms are still poorly understood. As an important cofactor, B-cell translocation gene 1 (BTG1) is involved in many physiologic processes; however, the direct effect of BTG1 on insulin sensitivity has not been described. In our study, BTG1 overexpression or knockdown improved or impaired insulin signaling in vitro, respectively. In addition, adenovirus-mediated BTG1 overexpression improved insulin sensitivity in wild-type (WT) and insulin-resistant leptin-receptor mutated (db/db) mice. In addition, transgenic BTG1-overexpressing mice were resistant to high-carbohydrate diet-induced insulin resistance. Adenovirus-mediated BTG1 knockdown consistently impaired insulin sensitivity in WT and insulin-sensitive leucine-deprived mice. Moreover, hepatic BTG1 expression was increased by leucine deprivation via the mammalian target of rapamycin/ribosomal protein S6 kinase 1 pathway. Furthermore, c-Jun expression was up-regulated by BTG1, and adenovirus-mediated c-Jun knockdown blocked BTG1-improved insulin signaling and insulin sensitivity in vitro and in vivo. Finally, BTG1 promoted c-Jun expression via stimulating c-Jun and retinoic acid receptor activities. Taken together, these results identify a novel function for BTG1 in the regulation of hepatic insulin sensitivity and provide important insights into the nutritional regulation of BTG1 expression.- Xiao, F., Deng, J., Yu, J., Guo, Y., Chen, S., Guo, F. A novel function of B-cell translocation gene 1 (BTG1) in the regulation of hepatic insulin sensitivity in mice via c-Jun.

  9. Aplicación de la Agenda 21 en los Planes de Desarrollo Concertado de las provincias del departamento de Junín

    Directory of Open Access Journals (Sweden)

    Hugo Miguel Miguel

    2015-06-01

    Full Text Available Este trabajo de investigación ha tenido como objetivo comprobar la influencia de la Agenda 21 en los planes de desarrollo concertado de los gobiernos locales provinciales del departamento de Junín mediante la inclusión de los indicadores de desarrollo sostenible. Para su ejecución se utilizó el método de investigación descriptivo correlacional. Los instrumentos aplicados fueron fichas de observación de 25 ítems, en función de la estructura lógica de la Agenda 21, dentro de esta: las dimensiones del desarrollo sostenible (económico, social y ambiental. La población de estudio estuvo conformada por los planes de desarrollo concertado de las nueve provincias del departamento de Junín. De la misma forma, la muestra censal estuvo compuesta por los nueve planes de desarrollo concertado provinciales de la región Junín. Algunos de los resultados obtenidos revelan que la influencia de la Agenda 21 en los planes de desarrollo de los gobiernos locales provinciales del departamento de Junín, mediante la inclusión de sus indicadores de desarrollo sostenible (inclusión del 23 % del total de indicadores no fue significativa (p > 0,05, ya que la prueba binomial presenta un valor p de 1, mayor que el nivel usual de significación de 0,05. En conclusión la Agenda 21 que promueve el desarrollo y la cooperación en la esfera del medio ambiente, no influyó significativamente en los planes de desarrollo concertado de los gobiernos locales provinciales del departamento de Junín, porque solo se incluyeron el 23 % de los indicadores de desarrollo sostenible.

  10. Radiation-induced apoptosis in developing rats and kainic acid-induced excitotoxicity in adult rats are associated with distinctive morphological and biochemical c-Jun/AP-1 (N) expression

    Energy Technology Data Exchange (ETDEWEB)

    Pozas, E. [Unitat de Neuropatologia, Servei d' Anatomia Patologica, Hospital Princeps d' Espanya, Universitat de Barcelona, 08907 Hospitalet de Llobregat (Spain); Planas, A.M. [Departament de Farmacologia i Toxicologia, IIBB, CSIC Barcelona (Spain); Ferrer, I. [Unitat de Neuropatologia, Servei d' Anatomia Patologica, Hospital Princeps d' Espanya, Universitat de Barcelona, 08907 Hospitalet de Llobregat (Spain)

    1997-07-14

    Ionizing radiation produces apoptosis in the developing rat brain. Strong c-Jun immunoreactivity, as revealed with the antibody c-Jun/AP-1 (N) which is raised against the amino acids 91-105 mapping with the amino terminal domain of mouse c-Jun p39, is simultaneously observed in the nucleus and cytoplasm of apoptotic cells. Western blotting of total brain homogenates, using the same antibody, shows a p39 band in control rats which is accompanied by a strong, phosphorylated p62 double-band in irradiated animals. In addition, increased c-Jun N-terminal kinase 1 expression, as found on western blots, is found in irradiated rats when compared with controls. Intraperitoneal injection of kainic acid at convulsant doses to the adult rat produces cell death with morphological features of necrosis, together with the appearance of cells with fine granular chromatin degeneration and small numbers of apoptotic-like cells, in the entorhinal and piriform cortices, basal amygdala, certain thalamic nuclei, and CA1 region of the hippocampus. c-Jun expression in kainic acid-treated rats, as revealed with the c-Jun/AP-1 (N) antibody, is found in the nuclei of a minority of cells in the same areas. The vast majority of c-Jun-immunoreactive cells have normal nuclear morphology, whereas necrotic cells are negative and only a few cells with fine granular chromatin condensation and apoptotic cells following kainic acid injection are stained with c-Jun antibodies. Western blotting, using the same antibody, shows a p39 band in control rats, which is accompanied by a band at about p26 from 6 h onwards following kainic acid injection. Decreased c-Jun N-terminal kinase 1 expression, as revealed on western blots, is observed in kainic acid-treated rats.These results show that the antibody c-Jun/AP-1 (N) recognizes three different forms of c-Jun-related immunoreactivity in normal and pathological states, which are associated with the different outcome of cells. These results stress the necessity

  11. JunD/AP-1 Antagonizes the Induction of DAPK1 To Promote the Survival of v-Src-Transformed Cells.

    Science.gov (United States)

    Maślikowski, Bart M; Wang, Lizhen; Wu, Ying; Fielding, Ben; Bédard, Pierre-André

    2017-01-01

    The increase in AP-1 activity is a hallmark of cell transformation by tyrosine kinases. Previously, we reported that blocking AP-1 using the c-Jun dominant negative mutant TAM67 induced senescence, adipogenesis, or apoptosis in v-Src-transformed chicken embryo fibroblasts (CEFs) whereas inhibition of JunD by short hairpin RNA (shRNA) specifically induced apoptosis. To investigate the role of AP-1 in Src-mediated transformation, we undertook a gene profiling study to characterize the transcriptomes of v-Src-transformed CEFs expressing either TAM67 or the JunD shRNA. Our study revealed a cluster of 18 probe sets upregulated exclusively in response to AP-1/JunD impairment and v-Src transformation. Four of these probe sets correspond to genes involved in the interferon pathway. One gene in particular, death-associated protein kinase 1 (DAPK1), is a C/EBPβ-regulated mediator of apoptosis in gamma interferon (IFN-γ)-induced cell death. Here, we show that inhibition of DAPK1 abrogates cell death in v-Src-transformed cells expressing the JunD shRNA. Chromatin immunoprecipitation data indicated that C/EBPβ was recruited to the DAPK1 promoter while the expression of a dominant negative mutant of C/EBPβ abrogated the induction of DAPK1 in response to the inhibition of AP-1. In contrast, as determined by chromatin immunoprecipitation (ChIP) assays, JunD was not detected on the DAPK1 promoter under any conditions, suggesting that JunD promotes survival by indirectly antagonizing the expression of DAPK1 in v-Src transformed cells. Transformation by the v-Src oncoprotein causes extensive changes in gene expression in primary cells such as chicken embryo fibroblasts. These changes, determining the properties of transformed cells, are controlled in part at the transcriptional level. Much attention has been devoted to transcription factors such as AP-1 and NF-κB and the control of genes associated with a more aggressive phenotype. In this report, we describe a novel mechanism

  12. Capacitaciones lúdicas en micro y pequeñas empresas del departamento de Junín

    Directory of Open Access Journals (Sweden)

    Roberto De La Torre Santana

    2015-06-01

    Full Text Available Los objetivos fueron, proponer metodologías lúdicas vivenciales de capacitación para medir su valoración por los pequeños y microempresarios de la región Junín; y demostrar la posibilidad de atender a este segmento de mercado con capacitaciones especializadas en centros adecuados. El estudio fue de caracter descriptivo y para la recopilación de datos se utilizó la técnica de la encuesta, aplicado a 803 pequeños y microempresarios de ocho zonas de la región Junín para conocer su periodicidad de capacitación, percepción frente a ella y su grado de conocimiento sobre las capacitaciones lúdicas. Sobre esta muestra fue determinada otra muestra para la realización de cuatro talleres de capacitación lúdica vivencial, orientados a comprobar la hipótesis; asimismo se aplicó la metodología de laboratorio de negocios de la OIT en 58 empresarios durante enero y febrero de 2014. Los resultados indican que el 100 % de los empresarios participantes en los cuatro talleres consideraron que la capacitación lúdica es de alta aplicabilidad para sus negocios; el 96,6 % la consideraron activa y nada aburrida; y el 100 % también mostraron su disposición de participar en más de estas capacitaciones, incluso propusieron una lista de cursos o temas que demandarían. En conclusión, las capacitaciones lúdicas son muy bien recibidas y valoradas por el 96,6 % de los empresarios que participaron en los talleres. Este segmento es muy importante y numeroso, que bien orientado y con productos de capacitación a su medida, puede aprovechar al máximo el mercado de capacitación lúdica.

  13. Effect of Qi-protecting powder (Huqi San) on expression of c-jun, c-fos and c-myc in diethylnitrosamine-mediated hepatocarcinogenesis

    Institute of Scientific and Technical Information of China (English)

    Xia Li; Zheng-Ming Shi; Ping Feng; Zhao-Yang Wen; Xue-Jiang Wang

    2007-01-01

    AIM: To study the inhibitory effect of Huqi San (Qiprotecting powder) on rat prehepatocarcinoma induced by diethylinitrosamine (DEN) by analyzing the mutational activation of c-fos proto-oncogene and over-expression of c-jun and c-myc oncogenes.METHODS: A Solt-Farber two-step test model of prehepatocarcinoma was induced in rats by DEN and 2-acetylaminofluorene (AAF) to investigate the modifying effects of Huqi San on the expression of c-jun, c-fos and c-myc in DEN-mediated hepatocarcinogenesis. Huqi San was made of eight medicinal herbs containing glycoprival granules, in which each milliliter contains 0.38 g crude drugs. γ-glutamy-transpeptidase-isoenzyme (γ-GTase)was determined with histochemical methods. Level of 8-hydroxydeoxyguanosine (OHdG) formed in liver and c-jun, c-fos and c-myc proto-oncogenes were detected by immunohistochemical methods.RESULTS: The level of 8-OHdG, a mark of oxidative DNA damage, was significantly decreased in the liver of rats with prehepatocarcinoma induced by DEN who received 8 g/kg body weight or 4 g/kg body weight Huqi San before (1 wk) and after DEN exposure (4 wk). Huqi Santreated rats showed a significant decrease in number of γ-GT positive foci (P < 0.001, prevention group: 4.96 ±0.72 vs 29.46 ± 2.17; large dose therapeutic group: 7.53± 0.88 vs 29.46 ± 2.17). On the other hand, significant changes in expression of c-jun, c-fos and c-myc were found in Huqi San-treated rats.CONCLUSION: Activation of c-jun, c-fos and c-myc plays a crucial role in the pathogenesis of liver cancer.Huqi San can inhibit the over-expression of c-jun, c-fos and c-myc oncogenes and liver preneolastic lesionsinduced by DEN.

  14. 蔡英文两岸论述解析%The Analysis of the Discourse of Cai Ying-wen on Cross-strait Relations

    Institute of Scientific and Technical Information of China (English)

    倪永杰

    2011-01-01

    民进党蔡英文的政策主张引起各方关注,其两岸论述既是选举策略,也反映了民进党当前的两岸思维与政策逻辑,对下阶段两岸关系的发展产生复杂影响。围绕2011年2月至6月间蔡英文公开发表的两岸言论进行分析,蔡的两岸论述在坚守"台独"内核的同时,持续进行策略调整,提出不少富有想象力的口号,但仍无法摆脱论述困境,陷于旧框架,缺乏新思维,两岸论述仍是民进党的重大"罩门"。%The policy advocated by Cai Ying-wen of Democratic Progressive Party attracted people's attention.Her discourse on cross-strait relations is not only her campaign strategy but also reflects the current logic thinking and policy of Democratic Progressive Party.It will have intricate influence on the development of cross-strait relations of the next stage.This article stresses and analyzes her two published speeches on cross-strait relations during Feb.to June of 2011.Although her discourse adheres to the kernel of "Taiwan independence" while continuing to undertake the adjustment strategy and bringing forward some imaginative slogans,she cannot get rid of the dilemma of her own discourse and it is immersed in the old framework of lacking fresh thought.Her cross-strait discourse is still the major "hood door" for Democratic Progressive Party.

  15. Fayalite-rich rims, veins, and halos around and in forsteritic olivines in CAIs and chondrules in carbonaceous chondrites: Types, compositional profiles and constraints of their formation

    Energy Technology Data Exchange (ETDEWEB)

    Hua, X.; Adam, J.; Palme, H.; Goresy, A. E. (Max-Planck-Institut fuer Kernphysik, Heidelberg (Germany, F.R.))

    1988-06-01

    Fayalite-rich rims, veins, and halos around and in forsteritic olivines are a wide-spread phenomenon in chondrules, Ca, Al-rich inclusions (CAIs), and single grains in carbonaceous chondrites. The presence of fayalite rod-like crystals and laths in rims, veins, in wall of pores, and as fluffy network bridging neighboring olivines, pyroxenes, feldspars, etc. is strongly suggestive that the fayalitic olivine was formed by condensation presumably from the solar nebula gas. The formation of the fayalitic olivine was probably caused by an increase in the H{sub 2}O/H{sub 2} ratio (to a ratio between 0.1-1) subsequent to condensation of forsterite. At that stage, FeNi inclusions in olivine were also oxidized and fayalitic halos around the metal were then formed Fe diffusion along with addition of SiO{sub 2} from the solar gas or loss of M{sub g}O to the solar gas. The Fa-rich olivine rims and veins display a narrow compositional variation between Fa{sup 34} and Fa{sup 46}. Subsequent to condensation of Fa-rich olivine and oxidation of FeNi metal, Fe diffused in forsterite. This diffusion was probable enhanced due to the presence of point defects in olivine or the formation of a nonstoichiometric phase analogous to laihunite enriched in Al{sub 2}O{sub 3} and Cr{sub 2}O{sub 3}. However, the presence of Al{sub 2}O{sub 3{minus}} and Cr{sub 2}O{sub 3{minus}} rich discrete domains cannot by excluded. Cooling rates calculated by modeling of the diffusion profiles are indicative of rapid cooling subsequent to the condensation of fayalitic olivines. The authors obtain cooling rates ranging from 2000{degree}/day and 10{degree}C/day at an initial temperature of 1200C{degree} and 900C{degree}, respectively.

  16. 蔡元培的建筑文化思想评述%Cai Yuanpei's Thought of Chinese Architectural Culture

    Institute of Scientific and Technical Information of China (English)

    宋卫忠

    2011-01-01

    Cai Yuanpei made great contributions to Chinese culture and education throughout his life,even in architectural culture,he is also very insightful.He insisted on architectural conception of democracy equality and humanism.Improving the living conditions of the sublayer,construction of various types of modern public cultural facilities,protection of the best folk architectural and cultural heritage,are important business that he always worked hardly.He stressed that the integration of Chinese and Western cultural concepts,advocated creating new cultural forms of modern architecture in China which is based this on the basis of national culture.%蔡元培一生为中国文化教育做出了巨大贡献,在建筑文化思想方面也是很有见地。他坚持民主平等和人本主义的建筑观念,积极投身于改善社会底层的居住状况、兴建各式近代公共文化设施、保护优秀民族建筑文化遗产等事业。在中西建筑文化关系方面,他强调中西融合的文化观念,主张在立足本民族文化基础上,通过兼收并蓄,创造出中国的近代建筑文化形式。

  17. Thermal and chemical evolution in the early Solar System as recorded by FUN CAIs: Part II - Laboratory evaporation of potential CMS-1 precursor material

    Science.gov (United States)

    Mendybaev, Ruslan A.; Williams, Curtis D.; Spicuzza, Michael J.; Richter, Frank M.; Valley, John W.; Fedkin, Alexei V.; Wadhwa, Meenakshi

    2017-03-01

    We present the results of laboratory experiments in which a forsterite-rich melt estimated to be a potential precursor of Allende CMS-1 FUN CAI was evaporated into vacuum for different lengths of time at 1900 °C. The evaporation of this melt resulted in residues that define trajectories in chemical as well as magnesium, silicon and oxygen isotopic composition space and come very close to the measured properties of CMS-1. The isotopic composition of the evaporation residues was also used to determine the kinetic isotopic fractionation factors [α2,1 (vapor-melt) defined as the ratio of isotopes 2 and 1 of a given element in the evaporating gas divided by their ratio in the evaporating source] for evaporation of magnesium (α25,24 for 25Mg/24Mg), silicon (α29,28 for 29Si/28Si) and oxygen (α18,16 for 18O/16O) from the forsterite-rich melt at 1900 °C. The values of α25,24 = 0.98383 ± 0.00033 and α29,28 = 0.99010 ± 0.00038 are essentially independent of change in the melt composition as evaporation proceeds. In contrast, α18,16 changes from 0.9815 ± 0.0016 to ∼0.9911 when the residual melt composition changes from forsteritic to melilitic. Using the determined values of α25,24 and α29,28 and present-day bulk chemical composition of the CMS-1, the composition of the precursor of the inclusion was estimated to be close to the clinopyroxene + spinel + forsterite assemblage condensed from a solar composition gas. The correspondence between the chemical composition and isotopic fractionation of experimental evaporation residues and the present-day bulk chemical and isotopic compositions of CMS-1 is evidence that evaporation played a major role in the chemical evolution of CMS-1.

  18. c-Jun N-terminal kinase (JNK signaling as a therapeutic target for Alzheimer´s disease

    Directory of Open Access Journals (Sweden)

    Ramón eYarza

    2016-01-01

    Full Text Available c-Jun N-terminal kinases (JNKs are a family of protein kinases that play a central role in stress signaling pathways implicated in gene expression, neuronal plasticity, regeneration, cell death and regulation of cellular senescence. It has been shown that there is a JNK pathway activation after exposure to different stressing factors, including cytokines, growth factors, oxidative stress, unfolded protein response signals or A peptides. Altogether, JNKs have become a focus of screening strategies searching for new therapeutic approaches to diabetes, cancer or liver diseases. In addition, activation of JNK has been identified as a key element responsible for the regulation of apoptotic apoptosis signals and therefore, it is critical for pathological occurring cell death associated with neurodegenerative diseases and, among them, with Alzheimer's disease (AD. In addition, in vitro and in vivo studies have reported alterations of JNK pathways potentially associated with pathogenesis and neuronal death in AD. JNK’s, particularly JNK3, not only enhance Aβ production, moreover it plays a key role in the maturation and development of neurofibrillary tangles.This review aims to explain the rationale behind testing therapies based on inhibition of JNK signalling for AD in terms of current knowledge about the pathophysiology of the disease. Keeping in mind that JNK3 is specifically expressed in the brain and activated by stress-stimuli, it is possible to hypothesize that inhibition of JNK3 might be considered as a potential target for treating neurodegenerative mechanisms associated with AD.

  19. Novel role of c-jun N-terminal kinase in regulating the initiation of cap-dependent translation.

    Science.gov (United States)

    Patel, Manish R; Sadiq, Ahad A; Jay-Dixon, Joe; Jirakulaporn, Tanawat; Jacobson, Blake A; Farassati, Faris; Bitterman, Peter B; Kratzke, Robert A

    2012-02-01

    Initiation of protein translation by the 5' mRNA cap is a tightly regulated step in cell growth and proliferation. Aberrant activation of cap-dependent translation is a hallmark of many cancers including non-small cell lung cancer. The canonical signaling mechanisms leading to translation initiation include activation of the Akt/mTOR pathway in response to the presence of nutrients and growth factors. We have previously observed that inhibition of c-jun N-terminal kinase (JNK) leads to inactivation of cap-dependent translation in mesothelioma cells. Since JNK is involved in the genesis of non-small cell lung cancer (NSCLC), we hypothesized that JNK could also be involved in activating cap-dependent translation in NSCLC cells and could represent an alternative pathway regulating translation. In a series of NSCLC cell lines, inhibition of JNK using SP600125 resulted in inhibition of 4E-BP1 phosphorylation and a decrease in formation of the cap-dependent translation complex, eIF4F. Furthermore, we show that JNK-mediated inhibition of translation is independent of mTOR. Our data provide evidence that JNK is involved in the regulation of translation and has potential as a therapeutic target in NSCLC.

  20. Differences in c-Jun N-terminal kinase recognition and phosphorylation of closely related stathmin-family members.

    Science.gov (United States)

    Yip, Yan Y; Yeap, Yvonne Y C; Bogoyevitch, Marie A; Ng, Dominic C H

    2014-03-28

    The stathmin (STMN) family of tubulin-binding phosphoproteins are critical regulators of interphase microtubule dynamics and organization in a broad range of cellular processes. c-Jun N-terminal kinase (JNK) signalling to STMN family proteins has been implicated specifically in neuronal maturation, degeneration and cell stress responses more broadly. Previously, we characterized mechanisms underlying JNK phosphorylation of STMN at proline-flanked serine residues (Ser25 and Ser38) that are conserved across STMN-like proteins. In this study, we demonstrated using in vitro kinase assays and alanine replacement of serine residues that JNK phosphorylated the STMN-like domain (SLD) of SCG10 on Ser73, consistent with our previous finding that STMN Ser38 was the primary JNK target site. In addition, we confirmed that a JNK binding motif ((41)KKKDLSL(47)) that facilitates JNK targeting of STMN is conserved in SCG10. In contrast, SCLIP was phosphorylated by JNK primarily on Ser60 which corresponds to Ser25 on STMN. Moreover, although the JNK-binding motif identified in STMN and SCG10 was not conserved in SCLIP, JNK phosphorylation of SCLIP was inhibited by a substrate competitive peptide (TI-JIP) highlighting kinase-substrate interaction as required for JNK targeting. Thus, STMN and SCG10 are similarly targeted by JNK but there are clear differences in JNK recognition and phosphorylation of the closely related family member, SCLIP.

  1. C-jun N-terminal Kinase-mediated Signaling Is Essential for Staphylococcus Aureus-induced U937 Apoptosis

    Institute of Scientific and Technical Information of China (English)

    Jia-he Wang; Bo Yu; Hui-yan Niu; Hui Li; Yi Zhang; Xin Wang; Ping He

    2009-01-01

    Objective To investigate the effect of SP600125, a specific c-jun N-terminal protein kinase (JNK) inhibitor, on Staphylococcus aureus (S. aureus)-induced U937 cell death and the underlying mechanism. Methods The human monocytic U937 cells were treated with S. aureus at different time with or without SP600125. Cell apoptosis was analyzed by flow cytometry. JNK, Bax, and caspase-3 activities were detected by Western blotting. Results S. aureus induced apoptosis in cultured U937 cells in a time-dependent manner. Expression of Bax and phospho-JNK significantly increased in S. aureus-treated U937 cells, and the level of activated caspase-3 also increased in a time-dependent manner. Inhibition of JNK with SP600125 significantly inhibited S. aureus-induced apoptosis in U937 cells. Conclusions S. aureus can induce apoptosis in U937 cells by phosphorylation of JNK and activation of Bax and caspase-3. SP600125 protects U937 cells from apoptosis induced by S. aureus via inhibiting the activity of JNK.

  2. Control of Oxidative Stress and Generation of Induced Pluripotent Stem Cell-like Cells by Jun Dimerization Protein 2

    Energy Technology Data Exchange (ETDEWEB)

    Chiou, Shyh-Shin, E-mail: chiouss@kmu.edu.tw [Division of Hematology-Oncology, Department of Pediatrics, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan (China); Department of Pediatrics, Faculty of Medicine, School of Medicine, Kaohsiung Medical University, 807 Kaohsiung 807, Taiwan (China); Wang, Sophie Sheng-Wen; Wu, Deng-Chyang [Department of Gastroenterology, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan (China); Lin, Ying-Chu [School of Dentistry, College of Dentistry, Kaohsiung Medical University, Kaohsiung 807, Taiwan (China); Kao, Li-Pin [Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, 807 Kaohsiung 807, Taiwan (China)

    2013-07-26

    We report here that the Jun dimerization protein 2 (JDP2) plays a critical role as a cofactor for the transcription factors nuclear factor-erythroid 2-related factor 2 (Nrf2) and MafK in the regulation of the antioxidants and production of reactive oxygen species (ROS). JDP2 associates with Nrf2 and MafK (Nrf2-MafK) to increase the transcription of antioxidant response element-dependent genes. Oxidative-stress-inducing reagent led to an increase in the intracellular accumulation of ROS and cell proliferation in Jdp2 knock-out mouse embryonic fibroblasts. In Jdp2-Cre mice mated with reporter mice, the expression of JDP2 was restricted to granule cells in the brain cerebellum. The induced pluripotent stem cells (iPSC)-like cells were generated from DAOY medulloblastoma cell by introduction of JDP2, and the defined factor OCT4. iPSC-like cells expressed stem cell-like characteristics including alkaline phosphatase activity and some stem cell markers. However, such iPSC-like cells also proliferated rapidly, became neoplastic, and potentiated cell malignancy at a later stage in SCID mice. This study suggests that medulloblastoma cells can be reprogrammed successfully by JDP2 and OCT4 to become iPSC-like cells. These cells will be helpful for studying the generation of cancer stem cells and ROS homeostasis.

  3. Involvement of hippocampal jun-N terminal kinase pathway in the enhancement of learning and memory by nicotine.

    Science.gov (United States)

    Kenney, Justin W; Florian, Cédrick; Portugal, George S; Abel, Ted; Gould, Thomas J

    2010-01-01

    Despite intense scrutiny over the past 20 years, the reasons for the high addictive liability of nicotine and extreme rates of relapse in smokers have remained elusive. One factor that contributes to the development and maintenance of nicotine addiction is the ability of nicotine to produce long-lasting modifications of behavior, yet little is known about the mechanisms by which nicotine alters the underlying synaptic plasticity responsible for behavioral changes. This study is the first to explore how nicotine interacts with learning to alter gene transcription, which is a process necessary for long-term memory consolidation. Transcriptional upregulation of hippocampal jun-N terminal kinase 1 (JNK1) mRNA was found in mice that learned contextual fear conditioning (FC) in the presence of nicotine, whereas neither learning alone nor nicotine administration alone exerted an effect. Furthermore, the upregulation of JNK1 was absent in beta2 nicotinic receptor subunit knockout mice, which are mice that do not show enhanced learning by nicotine. Finally, hippocampal JNK activation was increased in mice that were administered nicotine before conditioning, and the inhibition of JNK during consolidation prevented the nicotine-induced enhancement of contextual FC. These data suggest that nicotine and learning interact to alter hippocampal JNK1 gene expression and related signaling processes, thus resulting in strengthened contextual memories.

  4. Monosodium Urate in the Presence of RANKL Promotes Osteoclast Formation through Activation of c-Jun N-Terminal Kinase

    Directory of Open Access Journals (Sweden)

    Jung-Yoon Choe

    2015-01-01

    Full Text Available The aim of this study was to clarify the role of monosodium urate (MSU crystals in receptor activator of nuclear factor kB ligand- (RANKL- RANK-induced osteoclast formation. RAW 264.7 murine macrophage cells were incubated with MSU crystals or RANKL and differentiated into osteoclast-like cells as confirmed by staining for tartrate-resistant acid phosphatase (TRAP and actin ring, pit formation assay, and TRAP activity assay. MSU crystals in the presence of RANKL augmented osteoclast differentiation, with enhanced mRNA expression of NFATc1, cathepsin K, carbonic anhydrase II, and matrix metalloproteinase-9 (MMP-9, in comparison to RAW 264.7 macrophages incubated in the presence of RANKL alone. Treatment with both MSU crystals and RANKL induced osteoclast differentiation by activating downstream molecules in the RANKL-RANK pathway including tumor necrosis factor receptor-associated factor 6 (TRAF-6, JNK, c-Jun, and NFATc1. IL-1b produced in response to treatment with both MSU and RANKL is involved in osteoclast differentiation in part through the induction of TRAF-6 downstream of the IL-1b pathway. This study revealed that MSU crystals contribute to enhanced osteoclast formation through activation of RANKL-mediated pathways and recruitment of IL-1b. These findings suggest that MSU crystals might be a pathologic causative agent of bone destruction in gout.

  5. Metformin prevents endoplasmic reticulum stress-induced apoptosis through AMPK-PI3K-c-Jun NH2 pathway

    Science.gov (United States)

    Jung, T.W.; Lee, M.W.; Lee, Y.-J.; Kim, S.M.

    2012-01-01

    Type 2 diabetes mellitus is thought to be partially associated with endoplasmic reticulum (ER) stress toxicity on pancreatic beta cells and the result of decreased insulin synthesis and secretion. In this study, we showed that a well-known insulin sensitizer, metformin, directly protects against dysfunction and death of ER stress-induced NIT-1 cells (a mouse pancreatic beta cell line) via AMP-activated protein kinase (AMPK) and phosphatidylinositol-3 (PI3) kinase activation. We also showed that exposure of NIT-1 cells to metformin (5mM) increases cellular resistance against ER stress-induced NIT-1 cell dysfunction and death. AMPK and PI3 kinase inhibitors abolished the effect of metformin on cell function and death. Metformin-mediated protective effects on ER stress-induced apoptosis were not a result of an unfolded protein response or the induced inhibitors of apoptotic proteins. In addition, we showed that exposure of ER stressed-induced NIT-1 cells to metformin decreases the phosphorylation of c-Jun NH(2) terminal kinase (JNK). These data suggest that metformin is an important determinant of ER stress-induced apoptosis in NIT-1 cells and may have implications for ER stress-mediated pancreatic beta cell destruction via regulation of the AMPK-PI3 kinase-JNK pathway.

  6. Control of Oxidative Stress and Generation of Induced Pluripotent Stem Cell-like Cells by Jun Dimerization Protein 2

    Directory of Open Access Journals (Sweden)

    Naoto Yamaguchi

    2013-07-01

    Full Text Available We report here that the Jun dimerization protein 2 (JDP2 plays a critical role as a cofactor for the transcription factors nuclear factor-erythroid 2-related factor 2 (Nrf2 and MafK in the regulation of the antioxidants and production of reactive oxygen species (ROS. JDP2 associates with Nrf2 and MafK (Nrf2-MafK to increase the transcription of antioxidant response element-dependent genes. Oxidative-stress-inducing reagent led to an increase in the intracellular accumulation of ROS and cell proliferation in Jdp2 knock-out mouse embryonic fibroblasts. In Jdp2-Cre mice mated with reporter mice, the expression of JDP2 was restricted to granule cells in the brain cerebellum. The induced pluripotent stem cells (iPSC-like cells were generated from DAOY medulloblastoma cell by introduction of JDP2, and the defined factor OCT4. iPSC-like cells expressed stem cell-like characteristics including alkaline phosphatase activity and some stem cell markers. However, such iPSC-like cells also proliferated rapidly, became neoplastic, and potentiated cell malignancy at a later stage in SCID mice. This study suggests that medulloblastoma cells can be reprogrammed successfully by JDP2 and OCT4 to become iPSC-like cells. These cells will be helpful for studying the generation of cancer stem cells and ROS homeostasis.

  7. Role of the Caenorhabditis elegans Shc adaptor protein in the c-Jun N-terminal kinase signaling pathway.

    Science.gov (United States)

    Mizuno, Tomoaki; Fujiki, Kota; Sasakawa, Aya; Hisamoto, Naoki; Matsumoto, Kunihiro

    2008-12-01

    Mitogen-activated protein kinases (MAPKs) are integral to the mechanisms by which cells respond to physiological stimuli and a wide variety of environmental stresses. In Caenorhabditis elegans, the stress response is controlled by a c-Jun N-terminal kinase (JNK)-like mitogen-activated protein kinase (MAPK) signaling pathway, which is regulated by MLK-1 MAPK kinase kinase (MAPKKK), MEK-1 MAPK kinase (MAPKK), and KGB-1 JNK-like MAPK. In this study, we identify the shc-1 gene, which encodes a C. elegans homolog of Shc, as a factor that specifically interacts with MEK-1. The shc-1 loss-of-function mutation is defective in activation of KGB-1, resulting in hypersensitivity to heavy metals. A specific tyrosine residue in the NPXY motif of MLK-1 creates a docking site for SHC-1 with the phosphotyrosine binding (PTB) domain. Introduction of a mutation that perturbs binding to the PTB domain or the NPXY motif abolishes the function of SHC-1 or MLK-1, respectively, thereby abolishing the resistance to heavy metal stress. These results suggest that SHC-1 acts as a scaffold to link MAPKKK to MAPKK activation in the KGB-1 MAPK signal transduction pathway.

  8. Speciifc effects of c-Jun NH2-terminal kinase-interacting protein 1 in neuronal axons

    Institute of Scientific and Technical Information of China (English)

    Shu Tang; Qiang Wen; Xiao-jian Zhang; Quan-cheng Kan

    2016-01-01

    c-Jun NH2-terminal kinase (JNK)-interacting protein 3 plays an important role in brain-derived neurotrophic factor/tropomyosin-related kinase B (TrkB) anterograde axonal transport. It remains unclear whether JNK-interacting protein 1 mediates similar effects, or whether JNK-interacting protein 1 affects the regulation of TrkB anterograde axonal transport. In this study, we isolated rat embryonic hippocampus and cultured hippocampal neuronsin vitro. Coimmunoprecipitation results demonstrated that JNK-interacting protein 1 formed TrkB com-plexesin vitro andin vivo. Immunocytochemistry results showed that when JNK-interacting protein 1 was highly expressed, the distribution of TrkB gradually increased in axon terminals. However, the distribution of TrkB reduced in axon terminals after knocking out JNK-interact-ing protein 1. In addition, there were differences in distribution of TrkB after JNK-interacting protein 1 was knocked out compared with not. However, knockout of JNK-interacting protein 1 did not affect the distribution of TrkB in dendrites. These ifndings conifrm that JNK-inter-acting protein 1 can interact with TrkB in neuronal cells, and can regulate the transport of TrkB in axons, but not in dendrites.

  9. Specific effects of c-Jun NH2-terminal kinase-interacting protein 1 in neuronal axons

    Directory of Open Access Journals (Sweden)

    Shu Tang

    2016-01-01

    Full Text Available c-Jun NH2-terminal kinase (JNK-interacting protein 3 plays an important role in brain-derived neurotrophic factor/tropomyosin-related kinase B (TrkB anterograde axonal transport. It remains unclear whether JNK-interacting protein 1 mediates similar effects, or whether JNK-interacting protein 1 affects the regulation of TrkB anterograde axonal transport. In this study, we isolated rat embryonic hippocampus and cultured hippocampal neurons in vitro. Coimmunoprecipitation results demonstrated that JNK-interacting protein 1 formed TrkB complexes in vitro and in vivo. Immunocytochemistry results showed that when JNK-interacting protein 1 was highly expressed, the distribution of TrkB gradually increased in axon terminals. However, the distribution of TrkB reduced in axon terminals after knocking out JNK-interacting protein 1. In addition, there were differences in distribution of TrkB after JNK-interacting protein 1 was knocked out compared with not. However, knockout of JNK-interacting protein 1 did not affect the distribution of TrkB in dendrites. These findings confirm that JNK-interacting protein 1 can interact with TrkB in neuronal cells, and can regulate the transport of TrkB in axons, but not in dendrites.

  10. Expression and regulation of c-Jun N-terminal kinase (JNK) in endometrial cells in vivo and in vitro.

    Science.gov (United States)

    Kizilay, Gulnur; Cakmak, Hakan; Yen, Chih-Feng; Atabekoglu, Cem; Arici, Aydin; Kayisli, Umit Ali

    2008-10-01

    JNK(c-Jun N-terminal kinase) is one of the main types of mitogen-activated protein kinases. JNK modulates inflammation and apoptosis in response to stress. Our hypothesis is that temporal and spatial changes in JNK activity regulate inflammation in human endometrium and that fluctuation in estrogen and progesterone levels may play a role in JNK activation. Therefore, we aimed to determine total-(t-) and active-(phosphorylated, p-) JNK expression in endometrial tissues in vivo by immunohistochemistry, and in vitro by immunocytochemistry and Western blot analysis. Immunohistochemistry revealed moderate cytoplasmic and nuclear t-JNK immunoreactivity, and mostly nuclear p-JNK immunoreactivity throughout the menstrual cycle and early pregnancy. The highest p- and t-JNK immunoreactivity was detected in late secretory phase (P estrogen combined with progesterone (E(2) + P(4)) withdrawal from the culture conditions, compared to control and non-withdrawal groups (P < 0.05). Upon treatment with JNK inhibitor SP600125, we observed a significantly decreased interleukin (IL)-8 level (P < 0.05) in the presence and absence of E(2). These results demonstrate that JNK expression increases during the late secretory phase when the inflammatory response is highest. Inhibition of IL-8 expression by SP600125 suggests that JNK is involved in regulation of proinflammatory mediators of endometrium.

  11. Ofidismo en la provincia de Chanchamayo, Junín: Revisión de 170 casos consecutivos en el Hospital de Apoyo de La Merced.

    OpenAIRE

    2013-01-01

    Objetivo: Describir las características clínico-epidemiológicas del ofidismo en la provincia de Chanchamayo, Junín, Perú. Materiales y métodos: Se revisaron todas las historias clínicas de pacientes con diagnóstico de ofidismo en el “Hospital de Apoyo de La Merced” (HALM), Junín, Perú entre enero de 1998 y diciembre del 2000. Se recogieron datos de demográficos y clínico-epidemiológicos. Resultados: Las historias clínicas revisadas fueron 195, de estas, 170 fueron incluidas en el análisis. La...

  12. Phosphorylation of purified mitochondrial Voltage-Dependent Anion Channel by c-Jun N-terminal Kinase-3 modifies channel voltage-dependence

    Directory of Open Access Journals (Sweden)

    Rajeev Gupta

    2017-06-01

    Full Text Available Voltage-Dependent Anion Channel (VDAC phosphorylated by c-Jun N-terminal Kinase-3 (JNK3 was incorporated into the bilayer lipid membrane. Single-channel electrophysiological properties of the native and the phosphorylated VDAC were compared. The open probability versus voltage curve of the native VDAC displayed symmetry around the voltage axis, whereas that of the phosphorylated VDAC showed asymmetry. This result indicates that phosphorylation by JNK3 modifies voltage-dependence of VDAC.

  13. Characterization of human constitutive photomorphogenesis protein 1, a RING finger ubiquitin ligase that interacts with Jun transcription factors and modulates their transcriptional activity.

    Science.gov (United States)

    Bianchi, Elisabetta; Denti, Simona; Catena, Raffaella; Rossetti, Grazisa; Polo, Simona; Gasparian, Sona; Putignano, Stella; Rogge, Lars; Pardi, Ruggero

    2003-05-30

    RING finger proteins have been implicated in many fundamental cellular processes, including the control of gene expression. A key regulator of light-dependent development in Arabidopsis thaliana is the constitutive photomorphogenesis protein 1 (atCOP1), a RING finger protein that plays an essential role in translating light/dark signals into specific changes in gene transcription. atCOP1 binds the basic leucine zipper factor HY5 and suppresses its transcriptional activity through a yet undefined mechanism that results in HY5 degradation in response to darkness. Furthermore, the pleiotropic phenotype of atCOP1 mutants indicates that atCOP1 may be a central regulator of several transcriptional pathways. Here we report the cloning and characterization of the human orthologue of atCOP1. Human COP1 (huCOP1) distributes both to the cytoplasm and the nucleus of cells and shows a striking degree of sequence conservation with atCOP1, suggesting the possibility of a functional conservation as well. In co-immunoprecipitation assays huCOP1 specifically binds basic leucine zipper factors of the Jun family. As a functional consequence of this interaction, expression of huCOP1 in mammalian cells down-regulates c-Jun-dependent transcription and the expression of the AP-1 target genes, urokinase and matrix metalloproteinase 1. The RING domain of huCOP1 displays ubiquitin ligase activity in an autoubiquitination assay in vitro; however, suppression of AP-1-dependent transcription by huCOP1 occurs in the absence of changes in c-Jun protein levels, suggesting that this inhibitory effect is independent of c-Jun degradation. Our findings indicate that huCOP1 is a novel regulator of AP-1-dependent transcription sharing the important properties of Arabidopsis COP1 in the control of gene expression.

  14. c-Jun N-terminal kinase is required for vitamin E succinate-induced apoptosis in human gastric cancer cells

    Institute of Scientific and Technical Information of China (English)

    Kun Wu; Yan Zhao; Gui-Chang Li; Wei-Ping Yu

    2004-01-01

    AIM: To investigate the roles of c-Jun N-terminal kinase (JNK)signaling pathway in vitamin E succinate-induced apoptosis in human gastric cancer SGC-7901 cells.METHODS: Human gastric cancer cell lines (SGC-7901)were treated with vitamin E succinate (VES) at 5, 10, 20 mg/L.Succinic acid and vitamin E were used as vehicle controls and condition medium only as an untreated (UT) control.Apoptosis was observed by 4′, 6-diamidine-2′-phenylindole dihydrochloride (DAPI) staining for morphological changes and by DNA fragmentation for biochemical alterations.Western blot analysis was applied to measure the expression ofJNK and phosphorylated JNK. After the cells were transiently transfected with dominant negative mutant of JNK (DNJNK) followed by treatment of VES, the expression of JNK and c-Jun protein was determined.RESULTS: The apoptotic changes were observed after VES treatment by DNA fragmentation. DNA ladder in the 20 mg/L VES group was more clearly seen than that in 10 mg/L VES group and was not detected following treatment of UT control, succinate and vitamin E. VES at 5, 10 and 20 mg/L increased the expression of p-JNK by 2.5-, 2.8- and 4.2-fold, respectively. VES induced the phosphorylation of JNK beginning at 1.5 h and produced a sustained increase for 24 h with the peak level at 12 h. Transient transfection of DN-JNK blocked VES-triggered apoptosis by 52%. DN-JNK significantly increased the level of JNK, while decreasing the expression of VES-induced c-Jun protein.CONCLUSION: VES-induced apoptosis in human gastric cancer SGC-7901 cells involves JNK signaling pathway via c-Jun and its downstream transcription factor.

  15. The Expression of Fos, Jun and AP-1 DNA Binding Activity in Rat Supraoptic Nucleus Neurons Following Acute Versus Repeated Osmotic Stimulation

    Science.gov (United States)

    1995-06-22

    stimulation. This pattern has been observed previously in the hippocampus after treatment with the seizure-inducing drug , metrazole (Sonnenberg et al... fosB , and fra-1 and -2. fra refers to ~OS­ ~elated ~ntigen. Western blot experiments and employment of less stringent nucleic acid hybridization...fos, fra-l and fosB , only form heterodimeric complexes with Jun-related proteins (Nakabeppu et al., 1988; Rauscher et al., 1988b) The AP-l site of many

  16. Elevated cJUN expression and an ATF/CRE site within the ATF3 promoter contribute to activation of ATF3 transcription by the amino acid response

    OpenAIRE

    Fu, Lingchen; Kilberg, Michael S.

    2012-01-01

    Mammalian cells respond to amino acid deprivation through multiple signaling pathways referred to as the amino acid response (AAR). Transcription factors mediate the AAR after their activation by several mechanisms; examples include translational control (activating transcription factor 4, ATF4), phosphorylation (p-cJUN), and transcriptional control (ATF3). ATF4 induces ATF3 transcription through a promoter-localized C/EBP-ATF response element (CARE). The present report characterizes an ATF/C...

  17. MFHAS1 suppresses TLR4 signaling pathway via induction of PP2A C subunit cytoplasm translocation and inhibition of c-Jun dephosphorylation at Thr239.

    Science.gov (United States)

    Shi, Qiqing; Xiong, Bo; Zhong, Jing; Wang, Huihui; Ma, Duan; Miao, Changhong

    2017-08-01

    TLR4, an important Toll-like receptor in innate immunity, can be activated by LPS and induce proinflammatory cytokines to resist invasion of pathogenic microorganism, but excessive inflammation can trigger tissue injury. Many genes negatively regulate TLR4 signaling pathway. Recent studies found that malignant fibrous histiocytoma amplified sequence 1 (MFHAS1) suppressed the expression of cytokine IL6 in Raw264.7 cells stimulated by LPS, but the mechanisms remained unclear. This study investigated the role of MFHAS1 in TLR4 signaling pathway and the possible mechanisms implicated. The results indicated that the expression of MFHAS1 was significantly increased in cells stimulated with LPS. Up-regulation of MFHAS1 effectively suppressed inflammatory cytokine expression in cells exposed to LPS, whereas down-regulation of MFHAS1 markedly increased inflammatory cytokines expression. Co-immunoprecipitation, pull-down and immunofluorescence tests demonstrated that MFHAS1 combined with the B and C subunits of PP2A and induced cytoplasm translocation of the C subunit, leading to decrease dephosphorylation of c-Jun at Thr239 and increase degradation of c-Jun. Reduction of c-Jun protein results in decreased AP-1 activity, which is independent of inhibition of JNK or p38MAPK phosphorylation. Taken together, these results indicate that MFHAS1 suppresses TLR4 signaling pathway through induction of PP2A C subunit cytoplasm translocation and subsequent c-Jun degradation, leading finally to decrease AP-1 activity and cytokines expression. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Stability and DNA-binding ability of the bZIP dimers formed by the ATF-2 and c-Jun transcription factors.

    Science.gov (United States)

    Carrillo, R J; Dragan, A I; Privalov, P L

    2010-02-19

    The dimer formed by the ATF-2 and c-Jun transcription factors is one of the main components of the human interferon-beta enhanceosome. Although these two transcription factors are able to form two homodimers and one heterodimer, it is mainly the heterodimer that participates in the formation of this enhanceosome, binding specifically to the positive regulatory domain IV (PRDIV) site of the enhancer DNA. To understand this surprising advantage of the heterodimer, we investigated the association of these transcription factors using fragments containing the basic DNA-recognition segment and the basic leucine zipper domain (bZIP). It was found that the probability of forming the hetero-bZIP significantly exceeds the probability of forming homo-bZIPs, and that the hetero-bZIP interacts more strongly with the PRDIV site of the interferon-beta enhancer, especially in the orientation that places the folded ATF-2 basic segment in the upstream half of this asymmetric site. The effect of salt on the formation of the ATF-2/c-Jun dimer and on its ability to bind the target PRDIV site showed that electrostatic interactions between the charged groups of these proteins and with DNA play an essential role in the formation of the asymmetric ATF-2/c-Jun/PRDIV complex. 2009 Elsevier Ltd. All rights reserved.

  19. Role of areca nut induced JNK/ATF2/Jun axis in the activation of TGF-β pathway in precancerous Oral Submucous Fibrosis

    Science.gov (United States)

    Pant, Ila; Rao, S. Girish; Kondaiah, Paturu

    2016-01-01

    Oral submucous fibrosis (OSF) is potentially premalignant with progressive and irreversible extracellular matrix deposition accompanied by epithelial atrophy and like other fibrotic disorders, is primarily a TGF-β driven disease. OSF is caused by prolonged chewing of areca nut. Our previous studies reported a pivotal role for TGF-β activation and its effects contributing to OSF. However, the mechanism for activation of TGF-β signaling in OSF is still unknown. In this study we demonstrate activation of TGF-β signaling with sub-cytotoxic dose of areca nut in epithelial cells and discovered a key role for pJNK in this process. In good correlation; pJNK was detected in OSF tissues but not in normal tissues. Moreover, activation of JNK was found to be dependent on muscarinic acid receptor induced Ca2+/CAMKII as well as ROS. JNK dependent phosphorylation of ATF2/c-Jun transcription factors resulted in TGF-β transcription and its signaling. pATF2/p-c-Jun were enriched on TGF-β promoter and co-localized in nuclei of epithelial cells upon areca nut treatment. In corroboration, OSF tissue sections also had nuclear pATF2 and p-c-Jun. Our results provide comprehensive mechanistic details of TGF-β signaling induced by etiological agent areca nut in the manifestation of fibrosis which can lead to new therapeutic modalities for OSF. PMID:27708346

  20. Procedimiento para evaluar el impacto de la Maestría en Dirección en el CAI Arrocero “Sur del Jíbaro” sobre el desarrollo individual, empresarial y local.

    Directory of Open Access Journals (Sweden)

    Renier Esquivel García

    2008-07-01

    Full Text Available El objetivo general de la investigación es diseñar e implementar un procedimiento general para evaluar el impacto de la Maestría en Dirección que permita conocer los cambios realizados a la gestión empresarial en el CAI Arrocero “Sur del Jíbaro”. Los procedimientos hallados en la literatura se analizaron minuciosamente proponiéndose un procedimiento general para evaluar el impacto de la Maestría en Dirección que permita conocer los cambios realizados a la gestión empresarial en el CAI Arrocero “Sur del Jíbaro”. El mismo está estructurado en consta de cinco fases, en la primera se caracteriza la empresa, luego en la fase preparatoria, ocurre un acercamiento al departamento relacionado con el problema y se describe el Clima Organizacional, en la fase de ejecución se seleccionan los instrumentos y se aplican para conocer el impacto de la Maestría. En la cuarta fase se analizan los resultados de la aplicación de los instrumentos, y en la quinta se comprueba si se realizaron los pasos anteriores de acuerdo a lo planificado, para mejorar cualquier problema detectado con la aplicación del procedimiento. La información obtenida permitirá trazar un plan de acción para mejorar el subsistema. Seguidamente se implementó el procedimiento en el CAI Arrocero “Sur del Jíbaro”. El impacto es favorable porque los indicadores de impacto se encuentran entre 0,9 y 1 como se establece en la escala.

  1. 张采的叙事类散文探析--从“传状”文角度考察%Analysis of Zhang Cai's Narrative Prose From the Perspective of Biography

    Institute of Scientific and Technical Information of China (English)

    曾硕先

    2016-01-01

    Zhang Cai who was one of the two leaders of the Fushe Association , which was the most influential organization in the literary circles in the late Ming Dynasty .The narrative prose composed by Zhang Cai mainly referred to as the traditional biogra -phies of history and ancient prose .In which various literary views can be found since Wang Yangming period , and it advocated the Neo-Confucianism .As for the narrative skills , he was good at exhibiting characters by special environmental description and crea -ting a solemn, serene and simple style .The traditional biographies of history and ancient prose can represent Zhang Cai ’ s prose style.So, we can understand the ancient literary retro -movement of the Fushe Association by investigating them .%作为明末主秉文坛的复社“二张”之一,张采叙事散文的特点于思想内容上,一扫王阳明以来的文坛纷纭,恪守明经倡学,回归程朱理学范畴;在叙事技巧上,善于将人物置身于特别的场景中凸显人物性格,善于营造静穆朴实的文风。作为张采代表性的散文创作文体,“传状”文无疑是洞见复社文学复古运动的一条捷径。

  2. An Inquiry into TANG Jun-yi’s Conception of Philosophy%唐君毅哲学观探究

    Institute of Scientific and Technical Information of China (English)

    张海龙

    2014-01-01

    Of the Chinese philosophers and historians of philosophy in the 20th century, TANG Jun-yi is well-known for his unique conception of philosophy. The formative process of his idea can be roughly divided into two periods. In the first period, he developed an open-minded philosophical attitude toward all classics and theories, although he didn’t give a clear definition of philosophy at that time. This attitude had a direct influence on the direction and overall scope of his later study in philosophy. In the second period, TANG Jun-yi gave a clear definition of philosophy. In his mind, the reflection and inter-connectivity are the essence of philosophy, and he paid much attention to the inter-connectivity. According to this viewpoint, he divided Chinese philosophy into four parts, the theory of Ming Li, the theory of Tian Dao, the theory of Ren Dao and the theory of Ren Wen. He thought that the ultimate goal of philosophy is enlightenment which is beyond language. At last, he formed his own conception of philosophy, which has the characteristics of “openness and inclusiveness,” “emphasis on the value of human life” and “the revival of Confucian values.”%唐君毅哲学观的形成大致经历了前后两个时期。在前一时期,唐君毅虽然没有对哲学下过一个明确的定义,但其贯通中西古今、不拘于一经一典、一家一派的开放的哲学心灵和哲学态度已经形成,而且直接影响了其以后的哲学研究与其哲学创造的整体规模、走向;在后一时期,唐君毅对哲学有一个明确的定义,他视反思性和贯通性为哲学的本性,尤重贯通性。在此基础上他用中国哲学固有的名辞把哲学的内容划分为名理论、天道论、人道论、人文论四大部,并把哲学的最终目标确定在了离言成教上,从而形成了具有“开放性和综摄性”、“重视人的生命价值”、“儒家的价值归宗”等特点的哲学观。

  3. Molecular clone and characterization of c-Jun N-terminal kinases 2 from orange-spotted grouper, Epinephelus coioides.

    Science.gov (United States)

    Guo, Minglan; Wei, Jingguang; Zhou, Yongcan; Qin, Qiwei

    2016-02-01

    c-Jun N-terminal kinase 2 (JNK2) is a multifunctional mitogen-activated protein kinases involving in cell differentiation and proliferation, apoptosis, immune response and inflammatory conditions. In this study, we reported a new JNK2 (Ec-JNK2) derived from orange-spotted grouper, Epinephelus coioides. The full-length cDNA of Ec-JNK2 was 1920 bp in size, containing a 174 bp 5'-untranslated region (UTR), 483 bp 3'-UTR, and a 1263 bp open reading frame (ORF), which encoded a putative protein of 420 amino acids. The deduced protein sequence of Ec-JNK2 contained a conserved Thr-Pro-Tyr (TPY) motif in the domain of serine/threonine protein kinase (S-TKc). Ec-JNK2 has been found to involve in the immune response to pathogen challenges in vivo, and the infection of Singapore grouper iridovirus (SGIV) in vitro. Immunofluorescence staining showed that Ec-JNK2 was localized in the cytoplasm of grouper spleen (GS) cells, and moved to the nucleus after infecting with SGIV. Ec-JNK2 distributed in all immune-related tissues examined. After challenging with lipopolysaccharide (LPS), SGIV and polyriboinosinic polyribocytidylic acid (poly I:C), the mRNA expression of Ec-JNK2 was significantly (P orange-spotted grouper. Over-expressing Ec-JNK2 in fathead minnow (FHM) cells increased the SGIV infection and replication, while over-expressing the dominant-negative Ec-JNK2Δ181-183 mutant decreased it. These results indicated that Ec-JNK2 could be an important molecule in the successful infection and evasion of SGIV.

  4. c-Jun N-terminal kinase regulates mitochondrial bioenergetics by modulating pyruvate dehydrogenase activity in primary cortical neurons.

    Science.gov (United States)

    Zhou, Qiongqiong; Lam, Philip Y; Han, Derick; Cadenas, Enrique

    2008-01-01

    This study examines the role of c-jun N-terminal kinase (JNK) in mitochondrial signaling and bioenergetics in primary cortical neurons and isolated rat brain mitochondria. Exposure of neurons to either anisomycin (an activator of JNK/p38 mitogen-activated protein kinases) or H2O2 resulted in activation (phosphorylation) of JNK (mostly p46(JNK1)) and its translocation to mitochondria. Experiments with mitochondria isolated from either rat brain or primary cortical neurons and incubated with proteinase K revealed that phosphorylated JNK was associated with the outer mitochondrial membrane; this association resulted in the phosphorylation of the E(1alpha) subunit of pyruvate dehydrogenase, a key enzyme that catalyzes the oxidative decarboxylation of pyruvate and that links two major metabolic pathways: glycolysis and the tricarboxylic acid cycle. JNK-mediated phosphorylation of pyruvate dehydrogenase was not observed in experiments carried out with mitoplasts, thus suggesting the requirement of intact, functional mitochondria for this effect. JNK-mediated phosphorylation of pyruvate dehydrogenase was associated with a decline in its activity and, consequently, a shift to anaerobic pyruvate metabolism: the latter was confirmed by increased accumulation of lactic acid and decreased overall energy production (ATP levels). Pyruvate dehydrogenase appears to be a specific phosphorylation target for JNK, for other kinases, such as protein kinase A and protein kinase C did not elicit pyruvate dehydrogenase phosphorylation and did not decrease the activity of the complex. These results suggest that JNK mediates a signaling pathway that regulates metabolic functions in mitochondria as part of a network that coordinates cytosolic and mitochondrial processes relevant for cell function.

  5. 计算机辅助创新驱动的产品概念设计创新设想产生过程模型%Process model of new ideas generation for product conceptual design driven by CAI

    Institute of Scientific and Technical Information of China (English)

    张建辉; 檀润华; 张鹏; 曹国忠

    2013-01-01

    Generation of creative ideas was critical in the product conceptual design process. The obstacle to idea generation in the process was that desigers didn't make full use of knowledge in different fields. Theory of Inventive Problem Solving (TRIZ) based Computer-aided Innovation Systems (CAIs) provided a platform for knowledge application in different fields. Principles of creative idea generation driven by Computer-aided Innovation (CAI) was put forward, the inventive problem was solved based on the design scenario of CAIs, the extended solution space was set up by (Unexpected Discoveries)UXD which was implied in the source design in order to drive the generation of creative idea, then, an integrated process model of creative idea generation for product conceptual design driven by CAI was developed. Idea generation for a safety isolation butterfly valve was carried out using the process model and demonstrated its feasibility.%创新设想产生是产品概念设计阶段的关键环节,影响该阶段设想产生的障碍是设计人员不能很好地利用多学科领域的知识.鉴于此,基于发明问题解决理论的计算机辅助创新软件系统提供了应用多学科领域知识的一个平台.提出了计算机辅助创新驱动的创新设想产生原理,以计算辅助创新软件为设计场景进行问题求解,基于源设计中的未预见的发现建立扩展解空间,驱动创新设想产生,进而建立了计算机辅助创新驱动的产品概念设计创新设想产生过程模型.通过安全隔离蝶阀创新设想产生验证了该模型的可行性.

  6. 计算机辅助中学物理教学的特点及软件开发方向%Features of CAI in Middle School Physics Course and the Software Development Direction

    Institute of Scientific and Technical Information of China (English)

    李志刚; 聂运洁

    2003-01-01

    @@ 一、问题的提出 我国在中学物理教学中应用计算机,大约从一九八四年开始.随着信息技术教育在全国中学的开展和辅助教学软件的推广,从事CAI(计算机辅助教学)用于物理教学的队伍逐年扩大,研究成果每年都有所增加.

  7. Nerve growth factor downregulates c-jun mRNA and Caspase-3 in striate cortex of rats after transient global cerebral ischemia/reperfusion

    Institute of Scientific and Technical Information of China (English)

    Dacheng Jin; Tiemin Wang; Xiubin Fang

    2006-01-01

    BACKGROUND: Immediate early gene (LEG) c-jun is a sensitive marker for functional status of nerve cells.Caspase-3 is a cysteine protease,which is a critical regulator of apoptosis. The effect of exogenous nerve growth factor (NGF) on the expression of c-jun Mrna and Caspase-3 protein in striate cortex of rats with transient global cerebral ischemia/reperfusion (IR) is unclear.OBJECTIVE: To study the protective effect of exogenous NGF on the brain of rats with transient global cerebral IR and its effecting pathway by observing the expression of c-jun Mrna and Caspase-3 protein.DESIGN: Randomized controlled animal trial.SETTING: Department of Neural Anatomy, Institute of Brain,China Medical University.MATERTALS:Eighteen healthy male SD rats of clean grade, aged 1 to 3 months, with body mass of 250 to 300 g, were involved in this study. NGF was provided by Dalian Svate Pharmaceutical Co.,Ltd, c-jun in situ hybridization detection kit, Caspase-3 antibody and SABC kit were purchased from Boster Biotechnology Co. ,Ltd.METHODS: This trial was carried out in the Department of Neural Anatomy, Institute of Brain, China Medical University during September 2003 to April 2005. ①Experimental animals were randomized into three groups with 6 in each: sham-operation group,IR group and NGF group. ②After the rats were anesthetized,the bilateral common carotid arteries and right external carotid arteries of rats were bluntly dissected and bilateral common carotid arteries were clamped for 30 minutes with bulldog clamps. Reperfusion began after buldog clamps were removed. Normal saline of 1mL and NGF (1×106 U/L) of 1 Ml was injected into the common carotid artery of rats via right external carotid arteries in the IR group and NGF group respectively.The injection was conducted within 30 minutes, and then the right external carotid arteries were ligated. In the sham-operation group, occlusion of bilateral common carotid arteries and administration of drugs were phosphate buffer

  8. Effect of Fibre Level and Fibre Source on Gut Morphology and Micro-environment in Local (Mong Cai and Exotic (Landrace×Yorkshire Pigs

    Directory of Open Access Journals (Sweden)

    T. T. B. Ngoc

    2012-12-01

    Full Text Available The effect of genotype, fibre level and fibre source on gut morphology, environment and microflora was studied using 18 Mong Cai (MC and 18 Landrace×Yorkshire (LY pigs, aged around 60 d. The diets were based on maize, rice bran, soybean meal, fish meal and soybean oil, and cassava residue (CR or brewer’s grain (BG as fibrous ingredient sources in the high-fibre diets (HF. A low-fibre diet (LF, containing around 200 g NDF/kg dry matter (DM, was formulated without CR and BG as feed ingredients. The HF diets (HF-CR and HF-BG were formulated to contain around 270 g NDF/kg DM. The experiment was arranged according to a 2×3 factorial completely randomized design with six replications, and lasted 30 d. Crypt density in ileum was lowest (p<0.05 and villus height in jejunum and ileum were the greatest (p<0.05 in pigs fed diet HF-BG. Villus width in ileum was greatest in pigs fed diets HF-CR and HF-BG (p<0.05. Lactic acid bacteria (LAB counts in stomach were greatest (p<0.05 and E. coli counts in ileum and colon were lowest (p<0.05 in pigs fed diet HF-CR. The concentration of total organic acids in ileum, caecum and colon were greatest (p<0.05, and pH in ileum and colon were lowest (p<0.05 in pigs fed diet HF-CR. Crypt density in ileum was lowest, and villus height in ileum and villus width in jejunum and ileum was greatest in LY pigs (p<0.05. LAB counts in stomach and ileum were greatest, and E. coli counts in ileum were lowest in MC pigs (p<0.05. The concentration of total organic acids in ileum, caecum and colon were greatest (p<0.05 and pH lowest (p<0.05 in MC pigs.

  9. 红菜薹主要矿质元素的配合力分析%Combining ability of major mineral elements in purple Cai-tai

    Institute of Scientific and Technical Information of China (English)

    张艳; 徐跃进; 谭远宝; 李亭亭; 鲁凡; 万正杰

    2012-01-01

    The combining ability and genetic parameters were estimated for four major mineral ele-ments(Ca,Mg,Fe and Zn) in F1 progenies of 32 crossing combinations of purple Cai-tai with the incomplete diallel cross using 2 novel male sterile lines as female parents and 16 inbreed lines as male parents. The results showed that male sterile line Eru-5 and male parents D,E,F and H,which had high GCA on Ca,Mg, Fe and Zn, could be regarded as good parents. The combinations Eru-5 × G, Eru-5 × H and Eru-3×L had high SCA on Ca,Mg,Fe and Zn. The analysis of heritability revealed that the heredity of Ca was mainly controlled by additive effect; those of Mg and Zn were mainly controlled by additive and non-additive effects; and the heredity of Fe was mainly controlled by non-additive effects.%利用不完全双列杂交法,对新育成的红菜薹胞质雄性不育系Eru-3、Eru-5和16个父本材料配制的32个杂交组合进行主要矿质元素Ca、Mg、Fe、Zn的配合力和遗传力分析.结果表明:雄性不育系Eru-5和父本D、E、F和H的一般配合力较高,是提高杂种一代矿质元素含量的理想亲本;组合Eru-5×G、Eru-5×H和Eru-3×L具有较好的特殊配合力效应,是矿质营养价值较高的优良杂交组合.遗传力分析表明.Ca主要受基因加性效应控制,Mg、Zn的遗传由加性和非加性基因效应共同控制,Fe主要由非加性基因效应控制.

  10. “Outros lugares, começam aqui...” com O «muro vegetal» do Museu do Cais Branly em Paris

    Directory of Open Access Journals (Sweden)

    ISABELLE GUILLAUIC

    2010-06-01

    Full Text Available Este artigo é dedicado à arte, à arquitetura e à paisagem urbana através da análise do Museu do Cais Branly, em Paris, na margem esquerda do rio Sena, em um ambiente urbano marcado pelas exposições mundiais de 1889 e de 1937, (Champs de Mars, Trocadero, o Palais de Tokyo, o Grand Palace, Gare d'Orsay, etc.. Um dos indiscutíveis marcos dessa paisagem urbana é a Torre de Gustave Eiffel (1889, embora tenha sido necessário esperar a criação da série de pinturas de Robert Delaunay, para se fixar na imaginação parisiense a Torre Eiffel como monumento. Assim, uma vez que a arte pode servir de intérprete para mostrar um monumento, - eu faço o seguinte pressuposto: que a arte pode inversamente influenciar uma obra urbana, não só avalizando, mas desta vez em frente de sua criação. Branly é o caso em que a arte contemporânea (Novo Realismo, Arte Povera, etc, tem influenciado algumas diretrizes arquitetônicas. Isso introduz a seguinte observação, ou seja, que as coleções do museu Branly não “dialogam” somente entre si, mas também com as do Museu de Arte Moderna da Cidade de Paris que se localizam em frente a essa ultima. Neste contexto, a fachada do escritório administrativo do Museu, "vestida" pelo artista e naturalista francês Patrick Blanc, não pode ser vista como uma obra isolada, porque o "Muro Vegetal" é aqui uma parte do cenário urbano global destinado a criar um território que é uma passagem ou um "caminho que vai de um mundo para outros mundos". “Terra natal, outros lugares começam aqui...” - é o título da exposição realizada na Fundação Cartier, em Paris (2009, onde o filósofo Paul Virilio apresentou o seu conceito de "futurismo do instante", o que poderia ajudar a explicar a proliferação atual de muros vegetais em áreas urbanas.

  11. S-adenosyl-methionine decreases ethanol-induced apoptosis in primary hepatocyte cultures by a c-Jun N-terminal kinase activity-independent mechanism

    Institute of Scientific and Technical Information of China (English)

    María del Pilar Cabrales-Romero; Lucrecia Márquez-Rosado; Samia Fattel-Fazenda; Cristina Trejo-Solís; Evelia Arce-Popoca; Leticia Alemén-Lazarini; Saúl Villa-Trevi(n)o

    2006-01-01

    AIM: To determine the role of c-Jun N-terminal kinase (JNK) activity in ethanol-induced apoptosis and the modulation of this signaling cascade by S-Adenosylmethionine (AdoMet).METHODS: Primary hepatocyte cultures were pretreated with 100 μmol/L SP600125, a selective JNK inhibitor, 1 mL/L DMSO or 4 mmol/L AdoMet and then exposed to 100 mmo/L ethanol. Hepatocyte apoptosis was determined by the TUNEL and DNA ladder assays.JNK activity and its inhibition by SP600125 and AdoMet were determined by Western blot analysis of c-jun phosphorylation and Bid fragmentation. SP600125 and AdoMet effects on the apoptotic signaling pathway were determined by Western blot analysis of cytochrome c release and pro-caspase 3 fragmentation. The AdoMet effect on glutathione levels was measured by Ellman's method and reactive oxygen species (ROS) generation by cell cytometry.RESULTS: The exposure of hepatocytes to ethanol induced JNK activation, c-jun phosphorylation, Bid fragmentation, cytochrome c release and pro-caspase 3 cleavage; these effects were diminished by SP600125, and caused a significant decreasein ethanol-induced apoptosis (P< 0.05). AdoMet exerted an antioxidant effect maintaining glutathione levels and decreasing ROS generation, without a significant effect on JNK activity,and prevented cytochrome c release and pro-caspase 3 cleavage.CONCLUSION: The JNK signaling cascade is a key component of the proapoptotic signaling pathway induced by ethanol. JNK activation may be independent from ROS generation, since AdoMet which exerted antioxidant properties did not have a significant effect on JNK activity. JNK pathway modulator agents and AdoMet may be components of promising therapies for alcoholic liver disease (ALD) treatment.

  12. c-Jun NH2-terminal kinase-dependent upregulation of DR5 mediates cooperative induction of apoptosis by perifosine and TRAIL

    Directory of Open Access Journals (Sweden)

    Chen Georgia Z

    2010-12-01

    Full Text Available Abstract Background Perifosine, an alkylphospholipid tested in phase II clinical trials, modulates the extrinsic apoptotic pathway and cooperates with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL to augment apoptosis. The current study focuses on revealing the mechanisms by which perifosine enhances TRAIL-induced apoptosis. Results The combination of perifosine and TRAIL was more active than each single agent alone in inducing apoptosis of head and neck squamous cell carcinoma cells and inhibiting the growth of xenografts. Interestingly, perifosine primarily increased cell surface levels of DR5 although it elevated the expression of both DR4 and DR5. Blockade of DR5, but not DR4 upregulation, via small interfering RNA (siRNA inhibited perifosine/TRAIL-induced apoptosis. Perifosine increased phosphorylated c-Jun NH2-terminal kinase (JNK and c-Jun levels, which were paralleled with DR4 and DR5 induction. However, only DR5 upregulaiton induced by perifosine could be abrogated by both the JNK inhibitor SP600125 and JNK siRNA. The antioxidants, N-acetylcysteine and glutathione, but not vitamin C or tiron, inhibited perifosine-induced elevation of p-c-Jun, DR4 and DR5. Moreover, no increased production of reactive oxygen species was detected in perifosine-treated cells although reduced levels of intracellular GSH were measured. Conclusions DR5 induction plays a critical role in mediating perifosine/TRAIL-induced apoptosis. Perifosine induces DR5 expression through a JNK-dependent mechanism independent of reactive oxygen species.

  13. Sostenibilidad ambiental del sistema de producción de café orgánico en la región Junín

    Directory of Open Access Journals (Sweden)

    Fernando Suca Apaza

    2012-12-01

    Full Text Available Objetivo: Evaluar la sostenibilidad ambiental del sistema productivo del café orgánico en la región Junín, tomando como unidad de análisis de estudio la provincia de Satipo. Métodos: Se utilizó el análisis de la emergía, ésta caracteriza y construye el sistema productivo desde un enfoque sistémico; se cuantifica y analiza los principales flujos de recursos naturales y económicos, luego se calcula e interpreta los indicadores emergéticos del sistema. Resultados: El aporte de la economía presenta un 43,99%. Sobre los índices emergéticos, se obtuvieron una transformidad de 6,79E+05 seJ/J, renovabilidad de 34,28%, tasa de eficiencia emergética de 2,27; tasa de carga ambiental de 1,92; tasa de inversión emergética de 0,79 y un índice de sostenibilidad emergética de 1,19. Conclusiones: El sistema productivo de café orgánico de la región Junín presenta un buen nivel de organización; también presenta un mayor aporte de recursos de la naturaleza con respecto al aporte de la economía. Los indicadores emergéticos demostraron que el sistema de café orgánico presenta mayor eficiencia, mayor renovabilidad, menor impacto al ecosistema y buena contrapartida de la naturaleza a las inversiones de los productores. Por lo tanto, el sistema de producción de café orgánico de la región de Junín es sostenible ambientalmente.

  14. Differential induction of c-Jun and Fos-like proteins in rat hippocampus and dorsal striatum after training in two water maze tasks.

    Science.gov (United States)

    Teather, Lisa A; Packard, Mark G; Smith, Diane E; Ellis-Behnke, Rutledge G; Bazan, Nicolas G

    2005-09-01

    Research examining the neuroanatomical bases of memory in mammals suggests that the hippocampus and dorsal striatum are parts of independent memory systems that mediate "cognitive" and stimulus-response "habit" memory, respectively. At the molecular level, increasing evidence indicates a role for immediate early gene (IEG) expression in memory formation. The present experiment examined whether acquisition of cognitive and habit memory result in differential patterns of IEG protein product expression in these two brain structures. Adult male Long-Evans rats were trained in either a hippocampal-dependent spatial water maze task, or a dorsal striatal-dependent cued water maze task. Ninety minutes after task acquisition, brains were removed and processed for immunocytochemical procedures, and the number of cells expressing Fos-like immunoreactivity (Fos-like-IR) and c-Jun-IR in sections from the dorsal hippocampus and the dorsal striatum were counted. In the dorsal hippocampus of rats trained in the spatial task, there were significantly more c-Jun-IR pyramidal cells in the CA1 and CA3 regions, relative to rats that had acquired the cued task, yoked controls (free-swim), or naïve (home cage) rats. Relative to rats receiving cued task training and control conditions, increases in Fos-like IR were also observed in the CA1 region of rats trained in the spatial task. In rats that had acquired the cued task, patches of c-Jun-IR were observed in the posteroventral striatum; no such patches were evident in rats trained in the spatial task, yoked-control rats, or naïve rats. The results demonstrate that IEG protein product expression is up-regulated in a task-dependent and brain structure-specific manner shortly after acquisition of cognitive and habit memory tasks.

  15. Comportamiento de la eficiencia de los gobiernos locales de Junín mediante el análisis envolvente de datos

    Directory of Open Access Journals (Sweden)

    Ybnias Grijalva Yauri

    2015-12-01

    Full Text Available La investigación comprende el análisis de los niveles de eficiencia de los gobiernos locales de la región Junín, período 2009 - 2014, mediante el método de análisis envolvente de datos (DEA y el índice de Malmquist, que se aplican buscando el objetivo de identificar un conjunto de unidades de eficiencia que sirvan de referente a los gobiernos locales de la región y así impulsar el cumplimiento de la misión institucional y de las competencias de gobierno local y por ende promover el desarrollo integral de su jurisdicción . La hipótesis planteada fue que los gobiernos locales que reporten niveles de eficiencia alcanzarán el cumplimiento de su misión institucional y sus competencias así como el cumplimiento de sus funciones, logrando promover el desarrollo integral de su jurisdicción. Los resultados obtenidos, en función de tres competencias de los gobiernos locales (servicios públicos locales; organización del espacio físico y uso del suelo; servicios sociales locales, indican que los gobiernos locales de Junín no alcanzan niveles de eficiencia permanentes en el tiempo. En conclusión, no es posible identificar unidades de toma de decisiones (DMU de eficiencia que sirvan como referencia a los gobiernos locales de Junín, limitando el cumplimiento de su misión institucional y cabal desempeño de competencias y funciones, en desmedro del desarrollo económico y social de su jurisdicción.

  16. Aryl hydrocarbon receptor pathway activation enhances gastric cancer cell invasiveness likely through a c-Jun-dependent induction of matrix metalloproteinase-9

    Directory of Open Access Journals (Sweden)

    Song Xin

    2009-04-01

    Full Text Available Abstract Background Abberant aryl hydrocarbon receptor (AhR expression and AhR pathway activation are involved in gastric carcinogenesis. However, the relationship between AhR pathway activation and gastric cancer progression is still unclear. In present study, we used 2,3,7,8-tetrachlorodibenzo-para-dioxin (TCDD, a classic and most potent ligand of AhR, to activate AhR pathway and investigated the effect of AhR pathway activation on human gastric cancer AGS cell invasion and explored the corresponding mechanism. Results To determine whether AhR pathway can be activated in AGS cells, we examined the expression of CYP1A1, a classic target gene of AhR pathway, following TCDD exposure. RT-PCR and western blot analysis showed that both CYP1A1 mRNA and protein expression were increased in a dose-dependent manner following TCDD treatment and AhR antagonist resveratrol (RSV could reverse this TCDD-induced CYP1A1 expression. To determine whether TCDD treatment of AGS cells results in an induction of MMP-9 expression, we detected MMP-9 mRNA using RT-PCR and detected MMP-9 enzymatic activity using gelatin zymography. The results showed that both MMP-9 mRNA expression and enzymatic activity were gradually increased with the concentration increase of TCDD in media and these changes could be reversed by RSV treatment in a dose-dependent manner. To examine whether AhR activation-induced MMP-9 expression and activity in AGS cells results in increased migration and invasion, we performed wound healing migration assay and transwell migration and invasion assay. After TCDD treatment, the migration distance and the migration and invasion abilities of AGS cells were increased with a dose-dependent manner. To demonstrate AhR activation-induced MMP-9 expression is mediated by c-Jun, siRNA transfection was performed to silence c-Jun mRNA in AGS cells. The results showed that MMP-9 mRNA expression and activity in untreated control AGS cells were very weak; After TCDD

  17. La educación media estatal en Junín y la construcción de una sociedad más justa

    OpenAIRE

    2015-01-01

    En América Latina se observa la injusticia educativa y en Argentina (el Distrito de Junín incluido), a pesar del discurso oportunista de los gobernantes de turno, acontece algo similar. Permanentemente se declama por las élites gobernantes de los países desarrollados ―por casos, Estados Unidos y Canadá en América del Norte o Alemania, Francia y Gran Bretaña en la más lejana Europa― que la educación es el pilar fundamental sobre el que se asienta el progreso de los pueblos. En el mismo orden d...

  18. Streptococcus pneumoniae induced c-Jun-N-terminal kinase- and AP-1 -dependent IL-8 release by lung epithelial BEAS-2B cells

    Directory of Open Access Journals (Sweden)

    Rosseau Simone

    2006-07-01

    Full Text Available Abstract Background Although pneumococcal pneumonia is one of the most common causes of death due to infectious diseases, little is known about pneumococci-lung cell interaction. Herein we tested the hypothesis that pneumococci activated pulmonary epithelial cell cytokine release by c-Jun-NH2-terminal kinase (JNK Methods Human bronchial epithelial cells (BEAS-2B or epithelial HEK293 cells were infected with S. pneumoniae R6x and cytokine induction was measured by RT-PCR, ELISA and Bioplex assay. JNK-phosphorylation was detected by Western blot and nuclear signaling was assessed by electrophoretic mobility shift assay (EMSA and chromatin immunoprecipitation (ChIP. JNK was modulated by the small molecule inhibitor SP600125 and AP1 by transfection of a dominant negative mutant. Results S. pneumoniae induced the release of distinct CC and CXC, as well as Th1 and Th2 cytokines and growth factors by human lung epithelial cell line BEAS-2B. Furthermore, pneumococci infection resulted in JNK phosphorylation in BEAS-2B cells. Inhibition of JNK by small molecule inhibitor SP600125 reduced pneumococci-induced IL-8 mRNA expression and release of IL-8 and IL-6. One regulator of the il8 promoter is JNK-phosphorylated activator protein 1 (AP-1. We showed that S. pneumoniae time-dependently induced DNA binding of AP-1 and its phosphorylated subunit c-Jun with a maximum at 3 to 5 h after infection. Recruitment of Ser63/73-phosphorylated c-Jun and RNA polymerase II to the endogenous il8 promoter was found 2 h after S. pneumoniae infection by chromatin immunoprecipitation. AP-1 repressor A-Fos reduced IL-8 release by TLR2-overexpressing HEK293 cells induced by pneumococci but not by TNFα. Antisense-constructs targeting the AP-1 subunits Fra1 and Fra2 had no inhibitory effect on pneumococci-induced IL-8 release. Conclusion S. pneumoniae-induced IL-8 expression by human epithelial BEAS-2B cells depended on activation of JNK and recruitment of phosphorylated c-Jun

  19. Modulation of c-Jun NH2-Terminal (JNK) by Cholinergic Autoantibodies from Patients with Sjögren’s Syndrome

    OpenAIRE

    Borda, Enri Santiago; Passafaro, Daniela; Reina, Silvia; Sterin Borda, Leonor

    2017-01-01

    Background: We wanted to determine (via an immunopharmacological approach) whether the c-Jun NH2 terminal kinase (JNK) cascade is phosphorylated in the submandibular gland by carbachol and cholinergic autoantibodies (IgG) present in the sera of patients with primary Sjögren’s syndrome (pSS) by interaction and activation of salivary gland muscarinic acetylcholine receptors (mAChRs). Methods: The JNK, PGE2 and NOS assays were measured in rat sub- mandibular gland with pSS IgG and carbachol alon...

  20. Comportamiento de la eficiencia de los gobiernos locales de Junín mediante el análisis envolvente de datos

    OpenAIRE

    Ybnias Grijalva Yauri

    2015-01-01

    La investigación comprende el análisis de los niveles de eficiencia de los gobiernos locales de la región Junín, período 2009 - 2014, mediante el método de análisis envolvente de datos (DEA) y el índice de Malmquist, que se aplican buscando el objetivo de identificar un conjunto de unidades de eficiencia que sirvan de referente a los gobiernos locales de la región y así impulsar el cumplimiento de la misión institucional y de las competencias de gobierno local y por ende promover el desarroll...

  1. Exploration of Cai Yuanpei’s University Management Thought%蔡元培高校管理思想摭探

    Institute of Scientific and Technical Information of China (English)

    韩延明

    2015-01-01

    在中国新文化运动中,蔡元培作为开教育新风之先驱,其教育思想至今闪耀着可资借鉴之处。在高校目标管理方面,他在“自发状态”中积极进行探索和应用,强调德育、智育、体育、美育和劳动技术教育的和谐发展;在教学管理中,他从学制、讲义、教法、学风等方面进行全面改革;在师资管理方面,他首倡“兼容并蓄”,以六个“不论”“网罗众家”,并使其群雄竞赛,各显其能;同时又严治教风,倡导尊师重业;在科研管理方面,他倡导思想自由,通过建立学术社团、创设研究机构、创造良好科研氛围、激发师生的科研兴趣,使北大的科研风气为之一新;在学生管理方面,他支持学生的爱国运动,贯彻“五自”方针,引导学生自立,开阔学生思路,教育学生“礼貌”待人;在改革学校旧有组织管理形式与行政管理体制方面,他首倡男女同校,提议限制校长及各科学长的任期,力行教授治校,创办校役夜班,这都是开风气之先的创新举措。%As the pioneer of Chinese new culture movement,Cai Yuanpei has created a new edu-cation style and his education thought still shines with reference nowadays. For the university target management,he conducts active exploration and application in a spontaneous state. He emphasizes the harmonious development of moral,intellectual,physical,aesthetic,labor and technical education. As to the teaching management,he advocates comprehensive reform from the perspective of school system,hand-outs,teaching method and study style. For the faculty management,he initiates full inclusion and equi-tability,recruits public talents with the six irrespective to enhance competition. He also promotes strict teaching style governance and teacher respect. For the research management,he advocates thought free-dom and refreshes the Peking university’s research culture through

  2. 论泥盆纪和布克河珊瑚及其相关属*%HEBUKOPHYLLUM LIAO AND CAI (DEVONIAN RUGOSA) AND ITS RELATED GENERA

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    和布克河珊瑚(Hebukophyllum Liao and Cai,1987)产于新疆北部和布克赛尔蒙古族自治县上泥盆统洪 古勒楞组。该属的特征明显,描述清楚,个体发育各个阶段的图影齐全,而且在国际学术界已经得到不少珊瑚专家 的认可(Weyer,1994),但目前仍有一些学者主张将它视为Circellia Ye and Wang 1983的同义名(Yu,1988;Poty and Boland,1996;Boland,1997)。经最近对这2属模式标本的进一步深入研究表明,虽然Hebukophyllum成年期的特 征与Circellia,Conilophyllum,Siphonophyllia等属有某些相似之处,但其幼年期的隔壁强烈加厚并在个体中央形 成一个明显的轴管(aulos),明显不同于后3属。Hebukophyllum明显不属于caninoid型珊瑚;Circellia是一种隔壁 构造十分不发育的小单体珊瑚,也不属于caninoid型珊瑚;Conilophyllum Poty and Boland,1996和Siphonophyllia Scouler MS in McCoy,1844则属于典型的caninoid型珊瑚。因此,上述几个属之间并无密切的亲缘关系,它们应分 属于不同的科: Family (科) Amplexidae Chapman, 1893 Genus (属) Circellia Ye and Wang, 1983 Family (科) Laccophyllidae Grabau, 1928 Cenus (属) Hebukophyllum Liao and Cai, 1987 Family (科) Caninidae Fomichev, 1953 Genus (属) Conilophyllum Poty and Boland, 1996 Genus (属) Siphonophyllia Scouler MS in McCoy, 1844 本文曾在1999年9月在日本仙台市召开的第8次国际化石刺丝胞与多孔类大会上(8th International Sympo- slum on Fossil Cnidaria and Porifera)宣读,会上笔者曾与比利时珊瑚专家Poty博士进行了交流和讨论。会后我们又 特地向中国地质大学(武汉)王治平、叶干教授借阅了Circellia的模式标本进行了比较深入的研究。我们在此表示 衷心的感谢。

  3. Effect of ketamine anesthesia in early pregnancy on the c-fos mRNA and c-jun mRNA expression in offsprings of rats%孕早期氯胺酮麻醉对子代大鼠海马c-fos mRNA和c-jun mRNA表达的影响

    Institute of Scientific and Technical Information of China (English)

    李钢; 赵为禄; 罗佛全

    2010-01-01

    目的 探讨孕早期氯胺酮麻醉对子代大鼠海马c-fos mRNA和c-jun mRNA表达的影响.方法 孕5~13 d的SD大鼠30只,体重250~300 g,随机分为2组(n=15):对照组(C组)和氯胺酮组(K组).K组经尾静脉注射氯胺酮20 mg/kg,随后以130 mg·kg-1·h-1的速率静脉输注2 h;C组以等量生理盐水替代氯胺酮.子代大鼠于出生后20和30 d时测定认知功能,取海马组织,测定c-fosmRNA和c-jun mRNA表达水平并观察超微结构.结果 与C组比较,K组子代大鼠出生后30 d时认知功能测定第2天逃避潜伏期延长(P<0.05),海马c-fos mRNA和c-jun mRNA的表达水平差异无统计学意义,出生后20 d上述指标差异无统计学意义(P>0.05).K组海马神经元发生损伤.结论 孕早期氯胺酮麻醉抑制子代大鼠认知功能的机制与海马神经元受损有关,但与海马c-fos mRNA和c-jun mRNA表达无关.%Objective To investigate the effect of ketamine anesthesia in the early pregnancy on the c-fos mRNA and c-jun mRNA expression in the offsprings of rats. Methods Thirty pregnant SD rats at 5-13 days of gestation were randomly divided into control group and ketamine group (n = 15 each). Ketamine 20 mg/kg was injected intravenously through tail vein followed by 2 h infusion at a rate of 130 mg·kg-1 ·h-1 in ketmine group.While the equal volume of normal saline was given instead of ketamine in control group. The learning and memory function of the offsprings were tested by Morris water maze test on postnatal day 20 and 30. The hippocampal tissues were taken to detect the expression of c-fos mRNA and c-jun mRNA and to observe the ultrastructure. Results Compared with group C, the escape latency was significantly prolonged at 2 days during the test which was performed on postnatal day 30, but there was no significant difference in the expression of c-fos mRNA and c-jun mRNA on postnatal day 20 and 30 and in the indices mentioned above on postnatal day 20 in ketamine group (P >0.05). The

  4. The activation of p38 MAPK primarily contributes to UV-induced RhoB expression by recruiting the c-Jun and p300 to the distal CCAAT box of the RhoB promoter

    Energy Technology Data Exchange (ETDEWEB)

    Ahn, Jiwon [Genome Research Center, KRIBB, Daejeon 305-806 (Korea, Republic of); Department of Microbiology, Chungnam National University, Daejeon 305-764 (Korea, Republic of); Choi, Jeong-Hae; Won, Misun [Genome Research Center, KRIBB, Daejeon 305-806 (Korea, Republic of); Kang, Chang-Mo [Laboratory of Cytogenetics and Tissue Regeneration, KIRAMS, Seoul 139-706 (Korea, Republic of); Gyun, Mi-Rang [Genome Research Center, KRIBB, Daejeon 305-806 (Korea, Republic of); Functional Genomics, Korea University of Science and Technology, Daejeon 305-350 (Korea, Republic of); Park, Hee-Moon [Department of Microbiology, Chungnam National University, Daejeon 305-764 (Korea, Republic of); Kim, Chun-Ho, E-mail: chkim@kirams.re.kr [Laboratory of Cytogenetics and Tissue Regeneration, KIRAMS, Seoul 139-706 (Korea, Republic of); Chung, Kyung-Sook, E-mail: kschung@kribb.re.kr [Genome Research Center, KRIBB, Daejeon 305-806 (Korea, Republic of)

    2011-06-03

    Highlights: {yields} Regulation of transcriptional activation of RhoB is still unclear. {yields} We examine the effect of p38 MAPK inhibition, and c-Jun and RhoB depletion on UV-induced RhoB expression and apoptosis. {yields} We identify the regions of RhoB promoter necessary to confer UV responsiveness using pRhoB-luciferase reporter assays. {yields} c-Jun, ATF2 and p300 are dominantly associated with NF-Y on the distal CCAAT box. {yields} The activation of p38 MAPK primarily contribute to UV-induced RhoB expression by recruiting the c-Jun and p300 proteins on distal CCAAT box of RhoB promoter. -- Abstract: The Ras-related small GTP-binding protein RhoB is rapidly induced in response to genotoxic stresses caused by ionizing radiation. It is known that UV-induced RhoB expression results from the binding of activating transcription factor 2 (ATF2) via NF-Y to the inverted CCAAT box (-23) of the RhoB promoter. Here, we show that the association of c-Jun with the distal CCAAT box (-72) is primarily involved in UV-induced RhoB expression and p38 MAPK regulated RhoB induction through the distal CCAAT box. UV-induced RhoB expression and apoptosis were markedly attenuated by pretreatment with the p38 MAPK inhibitor. siRNA knockdown of RhoB, ATF2 and c-Jun resulted in decreased RhoB expression and eventually restored the growth of UV-irradiated Jurkat cells. In the reporter assay using luciferase under the RhoB promoter, inhibition of RhoB promoter activity by the p38 inhibitor and knockdown of c-Jun using siRNA occurred through the distal CCAAT box. Immunoprecipitation and DNA affinity protein binding assays revealed the association of c-Jun and p300 via NF-YA and the dissociation of histone deacetylase 1 (HDAC1) via c-Jun recruitment to the CCAAT boxes of the RhoB promoter. These results suggest that the activation of p38 MAPK primarily contributes to UV-induced RhoB expression by recruiting the c-Jun and p300 proteins to the distal CCAAT box of the RhoB promoter in

  5. Notexin upregulates Fas and FasL protein expression of human neuroblastoma SK-N-SH cells through p38 MAPK/ATF-2 and JNK/c-Jun pathways.

    Science.gov (United States)

    Chen, Ku-Chung; Chang, Long-Sen

    2010-04-01

    Notechis scutatus scutatus notexin induced an increase in Fas and FasL protein expression of human neuroblastoma SK-N-SH cells in a dose- and time-dependent manner. Moreover, notexin treatment upregulated transcription of Fas/FasL mRNA. Downregulation of FADD blocked notexin-induced procaspase-8 degradation and cleavage of Bid and rescued viability of notexin-treated cells. Upon exposure to notexin, activation of JNK and p38 MAPK was observed in SK-N-SH cells. Notexin-induced upregulation of Fas and FasL was suppressed by SB202190 (p38 MAPK inhibitor) and S600125 (JNK inhibitor). Downregulation of p38alpha MAPK and JNK1 by siRNA proved that upregulation of Fas/FasL was related to p38alpha MAPK and JNK1 activation. Notexin treatment evoked p38alpha MAPK-mediated ATF-2 phosphorylation and JNK1-mediated c-Jun phosphorylation. Knockdown of c-Jun and ATF-2 by siRNA or overexpression of dominant-negative c-Jun and ATF-2 revealed that both c-Jun and ATF-2 were crucial for Fas/FasL upregulation. Taken together, our data indicate that notexin-induced upregulation of Fas and FasL is triggered by p38 MAPK/ATF-2 and JNK/c-Jun signaling pathways in SK-N-SH cells. Copyright 2009 Elsevier Ltd. All rights reserved.

  6. El turismo y sus perspectivas para la región Junín, Perú

    Directory of Open Access Journals (Sweden)

    Angela Ríos Cardozo

    2014-12-01

    Full Text Available El turismo comprende las actividades que realizan las personas durante sus viajes y estancias en lugares distintos a su entorno habitual por un periódo consecutivo inferior a un año con fines de ocio, por negocios y otros motivos no relacionados con el ejercicio de una actividad remunerada en el lugar visitado. No es una industria en el sentido tradicional, por lo que no figura como tal en las clasificaciones utilizadas en la elaboración de las cuentas nacionales de un país. Involucra una serie de actividades tales como alojamiento, servicios de alimentación y bebidas, transporte, agencias de viaje, actividades recreativas y de esparcimiento, entre otras, por lo que su medición está determinada por la demanda, calculándose sus efectos en el consumo de los visitantes u oferta de bienes y servicios para satisfacer esta demanda. En el 2013 viajaron en el mundo 1 087 millones de personas, que contribuyeron con el 9 % del PIB mundial, el 6 % de las exportaciones totales y dieron empleo a una de cada 11 personas, tanto en las economías avanzadas como en las emergentes (1. El principal país receptor de viajeros en el mundo fue Francia, que al año 2012 recibió 83 millones de personas, seguido de Estados Unidos con 66 millones. El tercer lugar lo ocupó China con 57,7 millones, superando a España que recibió 57,5 millones. En América Latina, México recibió el mayor número de turistas con 23,4 millones; seguido por Brasil con 5,7 millones; Argentina con 5,6 millones; República Dominicana con 4,6 millones; Puerto Rico, con 3,0 millones; Chile con 3,5 millones; Cuba y Perú con 2,8 millones; Colombia con 2,1 millones y Uruguay con 2,7 millones. Independientemente del crecimiento mundial turístico, lo importante es que el impacto de crecimiento en nuestro país y en la región Junín está en avanzada. El Perú, el 2013, recibió del exterior 3,1 millones de turistas, lo que representaría apenas el 0,3 % del total mundial; sin embargo

  7. c-Jun N-terminal kinase is required for thermotherapy-induced apoptosis in human gastric cancer cells

    Institute of Scientific and Technical Information of China (English)

    Feng Xiao; Bin Liu; Qing-Xian Zhu

    2012-01-01

    AIM:To investigate the role of c-Jun N-terminal kinase (JNK) in thermotherapy-induced apoptosis in human gastric cancer SGC-7901 cells.METHODS:Human gastric cancer SGC-7901 cells were cultured in vitro.Following thermotherapy at 43 ℃ for 0,0.5,1,2 or 3 h,the cells were cultured for a further 24 h with or without the JNK specific inhibitor,SP600125 for 2 h.Apoptosis was evaluated by immunohistochemistry [terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)] and flow cytometry (Annexin vs propidium iodide).Cell proliferation was determined by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide.The production of p-JNK,Bcl-2,Bax and caspase-3 proteins was evaluated by Western blotting.The expression of JNK at mRNA level was determined by reverse transcription polymerase chain reaction.RESULTS:The Proliferation of gastric carcinoma SGC-7901 cells was significantly inhibited following thermotherapy,and was 32.7%,30.6%,43.8% and 52.9% at 0.5,1,2 and 3 h post-thermotherapy,respectively.Flow cytometry analysis revealed an increased population of SGC-7901 cells in G0/G1 phase,but a reduced population in S phase following therrnotherapy for 1 or 2 h,compared to untreated cells (P < 0.05).The increased number of SGC-7901 cells in G0/G1 phase was consistent with induced apoptosis (flow cytometry) following thermotherapy for 0.5,1,2 or 3 h,compared to the untreated group (46.5% ± 0.23%,39.9% ± 0.53%,56.6% ±0.35% and 50.4% ± 0.29% vs 7.3% ± 0.10%,P < 0.01),respectively.This was supported by the TUNEL assay (48.2% ± 0.4%,40.1% ± 0.2%,61.2% ± 0.29% and 52.0% ± 0.42% vs 12.2% ± 0.22%,P < 0.01) respectively.More importantly,the expression of p-JNK protein and JNK mRNA levels were significantly higher at 0.5 h than at 0 h post-treatment (P < 0.01),and peaked at 2 h.A similar pattem was detected for Bax and caspase-3 proteins.Bcl-2 increased at 0.5 h,peaked at 1 h,and then decreased

  8. Perfluorocarbon inhibits lipopolysaccharide-induced macrophage inflammatory protein-2 expression and activation of ATF-2 and c-Jun in A549 pulmonary epithelial cells.

    Science.gov (United States)

    Hu, Y; Li, C S; Li, Y Q; Liang, Y; Cao, L; Chen, L A

    2016-04-30

    The signaling pathway that mediates the anti-inflammatory effects of perfluorocarbon (PFC) in alveolar epithelial cells treated with lipopolysaccharide (LPS) remains unclear. To evaluate the role of macrophage-inflammatory protein-2 (MIP-2), four A549 treatment groups were utilized: (1) untreated control, (2) 10 μg/mL of LPS, (3) 10 μg/mL of LPS+30% PFC and (4) 30% PFC. MIP-2 mRNA expression was determined by qPCR and ELISA. Mitogen-activated protein kinase (MAPK) activation was determined by Western blot analysis, and MIP-2 expression was determined by qPCR following treatment with MAPK inhibitors. PFC suppressed LPS-induced MIP-2 mRNA levels (P≤0.035) and MIP-2 secretion (P≤0.046). LPS induced ATF-2 and c-Jun phosphorylation, which was suppressed by PFC. Finally, inhibitors of ERK, JNK, and p38 suppressed LPS-induced MIP-2 mRNA expression. Thus, PFC inhibits LPS-induced MIP-2 expression and ATF-2 and c-Jun phosphorylation. To fully explore the therapeutic potential of PFC for acute lung injury (ALI), in vivo analyses are required to confirm these effects.

  9. Induction of apoptosis by casticin in cervical cancer cells: reactive oxygen species-dependent sustained activation of Jun N-terminal kinase

    Institute of Scientific and Technical Information of China (English)

    Fanxiang Zeng; Li Tian; Fei Liu; Jianguo Cao; Meifang Quan; Xifeng Sheng

    2012-01-01

    Casticin,a polymethoxyflavone from Fructus viticis used as an anti-inflammatory agent in Chinese traditional medicine,has been reported to have anti-cancer activity.The purpose of this study was to examine the apoptotic activity of casticin on human cervical cancer cells and its molecular mechanism.We revealed a novel mechanism by which casticin-induced apoptosis occurs and showed for the first time that the apoptosis induced by casticin is mediated through generation of reactive oxygen species (ROS) and sustained activation of c-Jun N-terminal kinase (JNK) in HeLa cells.Casticin markedly increased the levels of intracellular ROS and induced the expression of phosphorylated JNK and cJun protein.Pre-treatment with N-acetylcvsteine and SP600125 effectively attenuated induction of apoptosis by casticin in HeLa cells.Moreover,casticin induced ROS production and apoptotic cell death in other cervical cancer cell lines,such as CasKi and SiHa.Importantly,casticin did not cause generation of ROS or induction of apoptosis in normal human peripheral blood mononuclear cells and embryonic kidney epithelium 293 cells.These results suggest that ROS generation and sustained JNK activation by casticin play a role in casticin-induced apoptosis and raise the possibility that treatment with casticin might be promising as a new therapy against human cervical cancer.

  10. Dynamic acetylation of all lysine 4-methylated histone H3 in the mouse nucleus: analysis at c-fos and c-jun.

    Directory of Open Access Journals (Sweden)

    Catherine A Hazzalin

    2005-12-01

    Full Text Available A major focus of current research into gene induction relates to chromatin and nucleosomal regulation, especially the significance of multiple histone modifications such as phosphorylation, acetylation, and methylation during this process. We have discovered a novel physiological characteristic of all lysine 4 (K4-methylated histone H3 in the mouse nucleus, distinguishing it from lysine 9-methylated H3. K4-methylated histone H3 is subject to continuous dynamic turnover of acetylation, whereas lysine 9-methylated H3 is not. We have previously reported dynamic histone H3 phosphorylation and acetylation as a key characteristic of the inducible proto-oncogenes c-fos and c-jun. We show here that dynamically acetylated histone H3 at these genes is also K4-methylated. Although all three modifications are proven to co-exist on the same nucleosome at these genes, phosphorylation and acetylation appear transiently during gene induction, whereas K4 methylation remains detectable throughout this process. Finally, we address the functional significance of the turnover of histone acetylation on the process of gene induction. We find that inhibition of turnover, despite causing enhanced histone acetylation at these genes, produces immediate inhibition of gene induction. These data show that all K4-methylated histone H3 is subject to the continuous action of HATs and HDACs, and indicates that at c-fos and c-jun, contrary to the predominant model, turnover and not stably enhanced acetylation is relevant for efficient gene induction.

  11. Moracin M inhibits airway inflammation by interrupting the JNK/c-Jun and NF-κB pathways in vitro and in vivo.

    Science.gov (United States)

    Lee, Ju Hee; Ko, Hae Ju; Woo, Eun-Rhan; Lee, Sang Kook; Moon, Bong Soo; Lee, Chan Woo; Mandava, Suresh; Samala, Mallesham; Lee, Jongkook; Kim, Hyun Pyo

    2016-07-15

    The therapeutic effectiveness of moracins as 2-arylbenzofuran derivatives against airway inflammation was examined. Moracin M, O, and R were isolated from the root barks of Morus alba, and they inhibited interleukin (IL)-6 production from IL-1β-treated lung epithelial cells (A549) at 101-00μM. Among them, moracin M showed the strongest inhibitory effect (IC50=8.1μM). Downregulation of IL-6 expression by moracin M was mediated by interrupting the c-Jun N-terminal kinase (JNK)/c-Jun pathway. Moracin derivatives inhibited inducible nitric oxide synthase (iNOS)-catalyzed NO production from lipopolysaccharide (LPS)-treated alveolar macrophages (MH-S) at 50-100μM. In particular, moracin M inhibited NO production by downregulating iNOS. When orally administered, moracin M (20-60mg/kg) showed comparable inhibitory action with dexamethasone (30mg/kg) against LPS-induced lung inflammation, acute lung injury, in mice with that of dexamethasone (30mg/kg). The action mechanism included interfering with the activation of nuclear transcription factor-κB in inflamed lungs. Therefore, it is concluded that moracin M inhibited airway inflammation in vitro and in vivo, and it has therapeutic potential for treating lung inflammatory disorders.

  12. Upregulation of Connexin 43 Expression Via C-Jun N-Terminal Kinase Signaling in Prion Disease.

    Science.gov (United States)

    Lee, Geon-Hwi; Jang, Byungki; Choi, Hong-Seok; Kim, Hee-Jun; Park, Jeong-Ho; Jeon, Yong-Chul; Carp, Richard I; Kim, Yong-Sun; Choi, Eun-Kyoung

    2016-01-01

    Prion infection leads to neuronal cell death, glial cell activation, and the accumulation of misfolded prion proteins. However, the altered cellular environments in animals with prion diseases are poorly understood. In the central nervous system, cells connect the cytoplasm of adjacent cells via connexin (Cx)-assembled gap junction channels to allow the direct exchange of small molecules, including ions, neurotransmitters, and signaling molecules, which regulate the activities of the connected cells. Here, we investigate the role of Cx43 in the pathogenesis of prion diseases. Upregulated Cx43 expression, which was dependent on c-Jun N-Terminal Kinase (JNK)/c-Jun signaling cascades, was found in prion-affected brain tissues and hippocampal neuronal cells. Scrapie infection-induced Cx43 formed aggregated plaques within the cytoplasmic compartments at the cell-cell interfaces. The ethidium bromide (EtBr) uptake assay and scrape-loading dye transfer assay demonstrated that increased Cx43 has functional consequences for the activity of Cx43 hemichannels. Interestingly, blockade of PrPSc accumulation reduced Cx43 expression through the inhibition of JNK signaling, indicating that PrPSc accumulation may be directly involved in JNK activation-mediated Cx43 upregulation. Overall, our findings describe a scrapie infection-mediated novel regulatory signaling pathway of Cx43 expression and may suggest a role for Cx43 in the pathogenesis of prion diseases.

  13. Activation of c-Jun N-terminal kinase and apoptosis in endothelial cells mediated by endogenous generation of hydrogen peroxide

    Science.gov (United States)

    Ramachandran, Anup; Moellering, Douglas; Go, Young-Mi; Shiva, Sruti; Levonen, Anna-Liisa; Jo, Hanjoong; Patel, Rakesh P.; Parthasarathy, Sampath; Darley-Usmar, Victor M.

    2002-01-01

    Reactive oxygen species have been implicated in the activation of signal transduction pathways. However, extracellular addition of oxidants such as hydrogen peroxide (H2O2) often requires concentrations that cannot be readily achieved under physiological conditions to activate biological responses such as apoptosis. Explanations for this discrepancy have included increased metabolism of H2O2 in the extracellular environment and compartmentalization within the cell. We have addressed this issue experimentally by examining the induction of apoptosis of endothelial cells induced by exogenous addition of H2O2 and by a redox cycling agent, 2,3-dimethoxy-1,4-naphthoquinone, that generates H2O2 in cells. Here we show that low nanomolar steady-state concentrations (0.1-0.5 nmol x min(-1) x 10(6) cells) of H2O2 generated intracellularly activate c-Jun N terminal kinase and initiate apoptosis in endothelial cells. A comparison with bolus hydrogen peroxide suggests that the low rate of intracellular formation of this reactive oxygen species results in a similar profile of activation for both c-Jun N terminal kinase and the initiation of apoptosis. However, a detailed analysis reveals important differences in both the duration and profile for activation of these signaling pathways.

  14. Dynamic acetylation of all lysine 4-methylated histone H3 in the mouse nucleus: analysis at c-fos and c-jun.

    Directory of Open Access Journals (Sweden)

    2005-12-01

    Full Text Available A major focus of current research into gene induction relates to chromatin and nucleosomal regulation, especially the significance of multiple histone modifications such as phosphorylation, acetylation, and methylation during this process. We have discovered a novel physiological characteristic of all lysine 4 (K4-methylated histone H3 in the mouse nucleus, distinguishing it from lysine 9-methylated H3. K4-methylated histone H3 is subject to continuous dynamic turnover of acetylation, whereas lysine 9-methylated H3 is not. We have previously reported dynamic histone H3 phosphorylation and acetylation as a key characteristic of the inducible proto-oncogenes c-fos and c-jun. We show here that dynamically acetylated histone H3 at these genes is also K4-methylated. Although all three modifications are proven to co-exist on the same nucleosome at these genes, phosphorylation and acetylation appear transiently during gene induction, whereas K4 methylation remains detectable throughout this process. Finally, we address the functional significance of the turnover of histone acetylation on the process of gene induction. We find that inhibition of turnover, despite causing enhanced histone acetylation at these genes, produces immediate inhibition of gene induction. These data show that all K4-methylated histone H3 is subject to the continuous action of HATs and HDACs, and indicates that at c-fos and c-jun, contrary to the predominant model, turnover and not stably enhanced acetylation is relevant for efficient gene induction.

  15. Expressão dos protooncogenes c-fos, c-myc e c-jun em miométrio normal e mioma humanos Expression of the protooncogenes c-fos, c-myc and c-jun in human normal miometrium and leiomyoma

    Directory of Open Access Journals (Sweden)

    Ana Luiza Ferrari

    2006-10-01

    Full Text Available OBJETIVO: Comparar a expressão gênica (mRNA e protéica dos protooncogenes c-fos, c-myc e c-jun em miométrio normal e mioma humanos. MÉTODOS: Foi realizado um estudo do tipo caso-controle. O material foi coletado de 12 pacientes submetidas a histerectomia no Hospital de Clínicas de Porto Alegre. A expressão do mRNA específico para c-myc, c-fos, c-jun e beta-microglobulina foi avaliada pela técnica de RT-PCR, utilizando primers específicos para cada gene. A expressão protéica destes protooncogenes foi avaliada através de Western blot com anticorpos específicos. RESULTADOS: Não houve diferença significativa para expressão gênica desses protooncogenes entre miométrio normal e mioma (c-myc: 0,87 ± 0,08 vs 0,87 ± 0,08, p = 0,952; c-fos: 1,10 ± 0,17 vs 1,01 ± 0,11, p = 0,21; c-jun: 1,03 ± 0,12 vs 0,96 ± 0,09, p = 0,168, respectivamente. Não houve diferença significativa para expressão protéica desses protooncogenes entre miométrio normal e mioma (c-myc: 1,36 ± 0,48 vs 1,53 ± 0,29, p = 0,569; c-fos: 8,85 ± 5,5 vs 6,56 ± 4,22, p = 0,434; e c-jun: 6,47 ± 3,04 vs 5,42 ± 2,03, p = 0,266, respectivamente. CONCLUSÃO: A expressão gênica (transcrição e a expressão protéica (tradução dos protooncogenes c-myc, c-fos e c-jun em mioma e miométrio normal são semelhantes.Uterine myomas are common benign tumors of the female genital tract. The expression of growth factor signal transduction cascade components including the protooncogenes c-myc, c-fos, and c-jun seem to be involved in the development of myomas. PURPOSE: To compare the gene (mRNA and protein expression of the protooncogenes c-fos, c-myc, and c-jun in human normal myometrium and leiomyoma. METHOD: A case-control study was performed. Samples were collected from 12 patients submitted to hysterectomy at the Hospital de Clínicas at Porto Alegre. The expression of the specific mRNA for c-myc, c-fos, c-jun, and beta-microglobulin was assessed through the RT

  16. Monitoramento costeiro das praias de São Bento do Norte e Caiçara do Norte RN: implicações para o pólo petrolífero de Guamaré

    OpenAIRE

    Tabosa, Werner Farkatt

    2002-01-01

    Esta dissertação apresenta os resultados de uma pesquisa desenvolvida na região de São Bento do Norte e Caiçara do Norte, litoral setentrional do Estado do Rio Grande do Norte, durante o período de Junho de 2000 a Agosto de 2001, no âmbito dos projetos MAMBMARÉ (CNPq/CTPETRO) e PROBRAL (CAPES/DAAD). O objetivo principal da pesquisa foi a caracterização da dinâmica sedimentar do litoral em questão, com base em dados relativos à dinâmica costeira (ventos, correntes, ondas e marés), levant...

  17. Cai Hua, L’homme pensé par l’homme, Du statut scientifique des sciences sociales Paris, PUF, 2008, 214 p. et Laurent Barry, La parenté, Paris, Gallimard, 2008, 567 p.

    OpenAIRE

    2009-01-01

    Deux ouvrages récents réintroduisent la Chine dans l’anthropologie de la parenté. Cai Hua et Laurent Barry sont tous deux des élèves de Françoise Héritier, qui a renouvelé au Collège de France la connaissance des systèmes de parenté africains, et leurs ouvrages, construits de façon parallèle, accordent une grande place aux systèmes Han. L’anthropologie de la parenté, fondée en 1870 par l’ouvrage de Lewis Henry Morgan, Systems of Consanguinity and Affinity of the Human Family, et relancée en 1...

  18. Successful Implementation of "Localization of Books and Pictorials" Strategy in China's International Communication-An Interview with Mr. Cai Mingzhao, Vice Minister of the State Council Information Office and President of China International Publishing Group

    Institute of Scientific and Technical Information of China (English)

    Wu Yan; Liu Yun

    2005-01-01

    @@ China sticks to the way of peace and development,its image of stability,strongness and responsibility as a big country has been recognized and concerned worldwide.And by what means are people of other countries timely informed of China's current situation of reform and opening-up, continuously soaring economy, process of building a harmonious and well-off society in an all-round way, tremendous changes of China and new look of the Chinese people?Recently, our staff reporters interviewed Mr. Cai Mingzhao, Vice Minister of the State Council Information Office and President of China International Publishing Group, who gave definite answers on the above-mentioned questions.

  19. 继续教育中计算机辅助数学课程的实践与探索%Exploring and Practice on Mathematics Teachers' Training about CAI

    Institute of Scientific and Technical Information of China (English)

    顿继安; 李冬红

    2001-01-01

    计算机“智能化”地进入数学教学是必然趋势,这需要教师观念的更新.在计算机辅助数学课程中,通过新技术参与的问题解决使得教师认识新技术的“智能”作用,认识现代数学观,进一步在转变教师的数学教学观和培养教学思维能力方面作了探索.%This paper introduced our work on mathematics teachers training about CAI: try to make the mathematics teachers to realize the new technology's intellectualized function in education.

  20. 符际翻译视角下蔡志忠《论语》漫画研究%A Study on Cai Zhizhong's Chinese-English Analects from the Perspective of Intersemiotic Translation

    Institute of Scientific and Technical Information of China (English)

    汤文华

    2014-01-01

    As the representative work of the Chinese culture, the Analects of Confucius has been translated by numerous domestic and overseas scholars. Among the different translation versions, Cai Zhizhong’s Chinese-English Analects is the most typical and best-selling one. The reason lies in that Cai Zhizhong interprets the complicated Confucian thoughts into simple ones through comics, and translates the words of Confucianism into nonverbal symbols. Therefore, this paper, from the perspective of Jakobson’s intersemiotic translation theory, intends to explore that the pictorial symbols can be used to explain the cultural issues in the Analects of Confucius. It is hoped that this study can help people take into consideration of the cross-cultural communication of the Analects of Confucius from diverse dimensions.%作为中国文化的主要代表,《论语》是国内外学者英译最多的典籍之一,在众多英译本中,蔡志忠的中英版《论语》漫画最为畅销。其原因在于蔡志忠以漫画形式将其中深奥的哲理明了化,即用非语言符号系统诠释儒家思想。借助雅各布森的符际翻译理论,指出蔡志忠《论语》漫画中的图像符号作为一种非语言符号,可以成为解释中国典籍外译的手段,从而引导我们对《论语》跨文化传播的多维度思考。

  1. Alternativas legales para negociación de la quinua de pequeños productores en la región Junín

    Directory of Open Access Journals (Sweden)

    Ricardo Solis Reategui

    2015-06-01

    Full Text Available El objetivo del presente trabajo es mostrar la situación de los pequeños productores de quinua de la región Junín y como la implementación que ya se ha dado en otras partes del país podrían mejorar su entorno con el uso de herramientas legales que podrían asegurar sus producciones a mejores precios y con mejor trato al productor original. Para la recopilación de la información se recurrió a la revisión de literatura especializada. Entre los hallazgos se puede mencionar que los pequeños productores expresan que los acopiadores y las empresas exportadoras no muestran interés alguno en apoyarlos. Para ellos el fin de los acopiadores y el exportador es lucrar a través de conseguir un menor precio en el productor. Entre las conclusiones del trabajo se puede mencionar que existe muy poca asociatividad en la región Junín, algunas instituciones del Estado y regionales apoyan el desarrollo asociativo pero de manera incipiente y con muy poca información. La quinua de la región Junín es considerada orgánica, y el precio que se paga por ella es bastante bajo respecto de la calidad de la misma comparativamente con la quinua de la costa, que trata de alcanzar el mismo precio pero con una producción intensiva con el uso de pesticidas y bioquímicos que limitan su ingreso a determinados mercados. Las autoridades locales y regionales deben ayudar a desarrollar pequeñas cadenas para mejorar la producción de quinua a través de asesoría técnica, consecuentemente un buen producto permitirá exigir un mejor precio y condiciones de pago.

  2. The Market of Yuzhou Jun-porcelain at the End of Qing Dynasty (II)%清末禹州钧瓷市场研究(二)

    Institute of Scientific and Technical Information of China (English)

    郑辉

    2015-01-01

    清代末年,甲午战争中失利的清政府,欲振兴实业,进行一系列工商改良举措,西学东渐之风盛行。复烧不久的禹州钧瓷,基于“清末新政”的实施,无论是产销模式或工艺技术,亦走上近代化之路。对于素有“钧都”之称的禹州地区,此段迎来近代化转折重要的历史轨辙,当今学界鲜有涉猎研究。笔者竭力搜集珍贵历史文献与档案资料,进行系统爬梳归纳,并结合社会学、历史学等多学科交叉,针对清末禹州钧瓷市场发展样态加以梳理钩沉,分析其中良益与罅隙,弥补部分此段历史的研究空白,不致此珍贵历史余绪毁弃湮没。%At the end of Qing Dynasty, Qing Government that was defeated in the Sino-Japanese War of 1894-1895 aimed to prosper industries and carried out a series of industrial and commercial reforms. There was a prevailing trend of learning from western nations. Yuzhou Jun-porcelain that had been reproduced not long ago also stepped on the path of modernization no matter in the mode of production and sales or processing technology under the inlfuence of “new policies at the end of Qing Dynasty”. Yuzhou, known as “the Capital of Jun-porcelain”, embraced the important historical transition at the end of Qing Dynasty. The current researches in the academic ifeld appear to be inadequate. The author tries to collect a large quantity of historical literatures and ifles, makes systematic summarization, combs up the development trend of the market of Jun-porcelain in detail by combining sociology, history and other disciplines, analyzes the advantages and limitations of the literatures to ifll in the research blank so that the precious history will not fall into oblivion.

  3. Experience of Professor ZHAO Li-jun on Treating Infantile Anorexia%赵历军教授治疗小儿厌食经验

    Institute of Scientific and Technical Information of China (English)

    闫丽丽

    2012-01-01

    根据赵历军教授多年的临床经验,认为小儿厌食的病因标为饮食、情志所伤,本为脾胃虚弱,治疗以健脾益气,益胃助食为主,取得明显效果.%Based on clinical experience in many years, professor ZHAO Li-jun considered that the etiological of infantile anorexia is damage by the diet and emtions.The root cause is weakness of the spleen and stomach.The treatment should mainly focus on invigorating the spleen, benefiting vital energy, benefiting the stomach and helping the digesdion.It gets obvious effects.

  4. The c-Jun N-terminal kinase prevents oxidative stress induced by UV and thermal stresses in corals and human cells

    Science.gov (United States)

    Courtial, Lucile; Picco, Vincent; Grover, Renaud; Cormerais, Yann; Rottier, Cécile; Labbe, Antoine; Pagès, Gilles; Ferrier-Pagès, Christine

    2017-01-01

    Coral reefs are of major ecological and socio-economic interest. They are threatened by global warming and natural pressures such as solar ultraviolet radiation. While great efforts have been made to understand the physiological response of corals to these stresses, the signalling pathways involved in the immediate cellular response exhibited by corals remain largely unknown. Here, we demonstrate that c-Jun N-terminal kinase (JNK) activation is involved in the early response of corals to thermal and UV stress. Furthermore, we found that JNK activity is required to repress stress-induced reactive oxygen species (ROS) accumulation in both the coral Stylophora pistillata and human skin cells. We also show that inhibiting JNK activation under stress conditions leads to ROS accumulation, subsequent coral bleaching and cell death. Taken together, our results suggest that an ancestral response, involving the JNK pathway, is remarkably conserved from corals to human, protecting cells from the adverse environmental effects. PMID:28374828

  5. c-Jun N-terminal kinase 3 expression in the retina of ocular hypertension mice: a possible target to reduce ganglion cell apoptosis

    Directory of Open Access Journals (Sweden)

    Yue He

    2015-01-01

    Full Text Available Glaucoma, a type of optic neuropathy, is characterized by the loss of retinal ganglion cells. It remains controversial whether c-Jun N-terminal kinase (JNK participates in the apoptosis of retinal ganglion cells in glaucoma. This study sought to explore a possible mechanism of action of JNK signaling pathway in glaucoma-induced retinal optic nerve damage. We established a mouse model of chronic ocular hypertension by reducing the aqueous humor followed by photocoagulation using the laser ignition method. Results showed significant pathological changes in the ocular tissues after the injury. Apoptosis of retinal ganglion cells increased with increased intraocular pressure, as did JNK3 mRNA expression in the retina. These data indicated that the increased expression of JNK3 mRNA was strongly associated with the increase in intraocular pressure in the retina, and correlated positively with the apoptosis of retinal ganglion cells.

  6. Stress-induced phosphorylation of c-Jun-N-terminal kinases and nuclear translocation of Hsp70 in the Wistar rat hippocampus

    Directory of Open Access Journals (Sweden)

    Adžić M.

    2009-01-01

    Full Text Available Glucocorticoids are key regulators of the neuroendocrine stress response in the hippocampus. Their action is partly mediated through the subfamily of MAPKs termed c-Jun-N-terminal kinases (JNKs,whose activation correlates with neurodegeneration. The stress response also involves activation of cell protective mechanisms through various heat shock proteins (HSPs that mediate neuroprotection. We followed both JNKs and Hsp70 signals in the cytoplasmic and nuclear compartments of the hippocampus of Wistar male rats exposed to acute, chronic, and combined stress. The activity of JNK1 was decreased in both compartments by all three types of stress, while the activity of cytoplasmic JNK2/3 was elevated in acute and unaltered or lowered in chronic and combined stress. Under all stress conditions, Hsp70 translocation to the nucleus was markedly increased. The results suggest that neurodegenerative signaling of JNKs may be counteracted by increase of nuclear Hsp70,especially under chronic stress.

  7. The legitimacy of the "National Reorganization Process" locally. Actors and discursive strategies around the First International Exhibition of Production, Industry and Commerce. Junín, 1977

    Directory of Open Access Journals (Sweden)

    Evangelina Máspoli

    2013-12-01

    Full Text Available This paper proposes to explore the strategies of legitimation that were deployed in a space bounded local during the first stage of the so-called "National Reorganization Process" in Argentina. From a vision focused on the actors, in the analysis of speech, and in the local history will be analyzed the speeches that officials and personalities of national importance, provincial and local made during the First International Exhibition that took place in the city of Buenos Aires (Junín in October 1977. They try to envision the ideals and representations constructed around the figure of the agricultural producers of the mayors and municipalities, as well as links with the symbolic dimension of authoritarian project which sought to sustain that dictatorship

  8. Chrysotile effects on the expression of anti-oncogene P53 and P16 and oncogene C-jun and C-fos in Wistar rats' lung tissues.

    Science.gov (United States)

    Cui, Yan; Wang, Yuchan; Deng, Jianjun; Hu, Gongli; Dong, Faqin; Zhang, Qingbi

    2017-09-13

    Chrysotile is the most widely used form of asbestos worldwide. China is the world's largest consumer and second largest producer of chrysotile. The carcinogenicity of chrysotile has been extensively documented, and accumulative evidence has shown that chrysotile is capable of causing lung cancer and other forms of cancer. However, molecular mechanisms underlying the tumorigenic effects of chrysotile remained poorly understood. To explore the carcinogenicity of chrysotile, Wistar rats were administered by intratracheal instillation (by an artificial route of administration) for 0, 0.5, 2, or 8 mg/ml of natural chrysotile (from Mangnai, Qinghai, China) dissolved in saline, repeated once a month for 6 months (a repeated high-dose exposure which may have little bearing on the effects following human exposure). The lung tissues were analyzed for viscera coefficients and histopathological alterations. Expression of P53, P16, C-JUN, and C-FOS was measured by western blotting and qRT-PCR. Our results found that chrysotile exposure leads the body weight to grow slowly and lung viscera coefficients to increase in a dose-dependent manner. General sample showed white nodules, punctiform asbestos spots, and irregular atrophy; moreover, HE staining revealed inflammatory infiltration, damage of alveolar structures, agglomerations, and pulmonary fibrosis. In addition, chrysotile can induce inactivation of the anti-oncogene P53 and P16 and activation of the proto-oncogenes C-JUN and C-FOS both in the messenger RNA and protein level. In conclusion, chrysotile induced an imbalanced expression of cancer-related genes in rats' lung tissue. These results contribute to our understanding of the carcinogenic mechanism of chrysotile.

  9. Effect of different therapies of Chinese medicine on the expressions of c-Fos and c-Jun proteins in hippocampus of rats with post-stroke depression

    Institute of Scientific and Technical Information of China (English)

    Hongyan Wang; Mei Chen; Binhui Zhang

    2006-01-01

    BACKGROUND: c-fos and c-jun, the important immediate early genes (IEG), are regarded as the markers for the location and function of neuronal activity, as well as the third signal messengers, they couple the stress stimulation and the gene expression in neuron, and hippocampus is involved in the process of signal transmission after stress stimulation induced depression.OBJECTIVE: To observe the therapeutic effects of Bushen Yiqi (tonifying kidney to benefit qi), Huoxue Huayu (promoting blood circulation to dissipate blood stasis) and Ditan Kaiqiao (eliminating phlegm for resuscitation) on the expressions of c-Fos and c-Jun proteins in hippocampus and spontaneous behaviors of rats with post-stroke depression (PSD), and compare the results with those of fluoxetine, which is known to have definite effect on depression.DESIGN: A randomized controlled trial.SETrING: Zhejiang College of Traditional Chinese Medicine.MATERIALS: The trial was completed in Zhejiang College of Traditional Chinese Medicine from January to July in 2003. Fifty-six healthy adult Wistar male rats of clean grade, weighing (250±50) g, were randomly divided into 7 groups with 8 rats in each group: control group, model group, forced swimming group,Bushen Yiqi group; Huoxue Huayu, Ditan Kaiqiao group and fluoxetine group. The Bushen Yiqi Tang con tained Renshen, Huangqi, Heshouwu, Gouqi, Shudi, etc., crude drugs 1 800 g/L. The Huoxue Huayu Tang contained Danshen, Chuanxiong, Chishao, Yujin, etc., crude drugs 3 600 g/L. The Dian Kaiqiao Tang contained Banxia, Danxing, Changpu, Yuanzhi, etc., crude drug 1 000 g/L.METHODS: ① Except the control group and forced swimming group, rats in the other groups were made into PSD models by deligating the bilateral common carotid arteries permanently. ② Rats in the control group, model group and forced swimming group were intragastrically perfused by saline (3 mL for each time); those in the Bushen Yiqi group, Huoxue Huayu, Ditan Kaiqiao group and fluoxetine

  10. Capacidad antioxidante de poblaciones silvestres de “tara” (Caesalpinia spinosa de las localidades de Picoy y Santa Fe (Provincia de Tarma, departamento de Junín

    Directory of Open Access Journals (Sweden)

    Alberto López S.

    2011-01-01

    Full Text Available El Perú es el principal abastecedor de “tara”, gracias a que nuestro país posee una gran variedad de climas y tipos de suelos, haciendo posible la obtención de este cultivo durante la mayor parte del año. El departamento de Junín cuenta con poblaciones naturales de “tara” que aun no han sido caracterizadas bioquímica ni genéticamente, que podrían aprovecharse en beneficio de las comunidades locales. En este trabajo se reporta la capacidad antioxidante de “tara” provenientes de las localidades de Picoy y Santa Fe, ambas ubicadas en Tarma, Junín. Se utilizó la técnica del DPPH y del ABTS para valorar la capacidad antioxidante; para la determinación de fenoles y flavonoides se utilizó el reactivo de Folin-Ciocalteau según la técnica de Singleton. La muestra de Picoy reportó mayor cantidad de fenoles siendo de 563.70 mg/g de extracto seco, mientras que la cantidad de flavonoides fue de 0.664 mg/g. La capacidad antioxidante mostro una mejor respuesta en la muestra de Picoy, reportándose mediante el DPPH un IC50 1.244 mg/ml y con el ABTS un 35.3% de inhibición. Estos datos podrían aprovecharse para incrementar el valor agregado y mejorar la oferta de este recurso en dicha localidad debido a sus mejores características antioxidantes.

  11. Parathyroid hormone-related protein inhibits DKK1 expression through c-Jun-mediated inhibition of β-catenin activation of the DKK1 promoter in prostate cancer.

    Science.gov (United States)

    Zhang, H; Yu, C; Dai, J; Keller, J M; Hua, A; Sottnik, J L; Shelley, G; Hall, C L; Park, S I; Yao, Z; Zhang, J; McCauley, L K; Keller, E T

    2014-05-08

    Prostate cancer (PCa)bone metastases are unique in that majority of them induce excessive mineralized bone matrix, through undefined mechanisms, as opposed to most other cancers that induce bone resorption. Parathyroid hormone-related protein (PTHrP) is produced by PCa cells and intermittent PTHrP exposure has bone anabolic effects, suggesting that PTHrP could contribute to the excess bone mineralization. Wnts are bone-productive factors produced by PCa cells, and the Wnt inhibitor Dickkopfs-1 (DKK1) has been shown to promote PCa progression. These findings, in conjunction with the observation that PTHrP expression increases and DKK1 expression decreases as PCa progresses, led to the hypothesis that PTHrP could be a negative regulator of DKK1 expression in PCa cells and, hence, allow the osteoblastic activity of Wnts to be realized. To test this, we first demonstrated that PTHrP downregulated DKK1 mRNA and protein expression. We then found through multiple mutated DKK1 promoter assays that PTHrP, through c-Jun activation, downregulated the DKK1 promoter through a transcription factor (TCF) response element site. Furthermore, chromatin immunoprecipitation (ChIP) and re-ChIP assays revealed that PTHrP mediated this effect through inducing c-Jun to bind to a transcriptional activator complex consisting of β-catenin, which binds the most proximal DKK1 promoter, the TCF response element. Together, these results demonstrate a novel signaling linkage between PTHrP and Wnt signaling pathways that results in downregulation of a Wnt inhibitor allowing for Wnt activity that could contribute the osteoblastic nature of PCa.

  12. Malnutrición del adulto mayor y factores asociados en el distrito de Masma Chicche, Junín, Perú

    Directory of Open Access Journals (Sweden)

    Ana Lucía Contreras

    2013-07-01

    Full Text Available Objetivo: Determinar el estado nutricional y los factores asociados a malnutrición en el adulto mayor en la comunidad de Masma Chicche, Junín. Material y métodos: Estudio descriptivo transversal realizado en personas mayores de 60 años distrito de Masma Chicche, Junín, Perú. Se utilizó el Mini Nutritional Assesment (MNA para la evaluación nutricional e instrumentos de valoración geriátrica integral para establecer la presencia de depresión (Yesavage, estado funcional (Katz, deterioro cognitivo (Pfeiffer, salud oral (GOHA y estado social (Guijon. Se realizó estadística descriptiva, chi cuadrado y ANOVA para determinar asociación entre las variables. Se consideró un p < 0,05 como significativo. Resultados: Se encuestaron a 72 personas. La prevalencia de malnutrición fue 29,9%; 57,9% en riesgo de malnutrición. El 69,4% presentaban depresión y riesgo de la misma; 27,8% mostró deterioro cognitivo; 93,1% presentaba percepción negativa de su salud oral; 51,4% eran dependientes funcionales y el 100% poseía algún problema social. Se encontró asociación de malnutrición con las variables, sexo masculino y presencia de depresión. Conclusiones: En la comunidad de Masma Chicche, alrededor de la tercera parte de la población tiene malnutrición la que está asociada con el sexo masculino y la presencia de depresión.

  13. GDNF-independent ureteric budding: role of PI3K-independent activation of AKT and FOSB/JUN/AP-1 signaling

    Directory of Open Access Journals (Sweden)

    James B. Tee

    2013-07-01

    A significant fraction of mice deficient in either glial cell-derived neurotrophic factor (GDNF or its co-receptors (Gfrα1, Ret, undergoes ureteric bud (UB outgrowth leading to the formation of a rudimentary kidney. Previous studies using the isolated Wolffian duct (WD culture indicate that activation of fibroblast growth factor (FGF receptor signaling, together with suppression of BMP/Activin signaling, is critical for GDNF-independent WD budding (Maeshima et al., 2007. By expression analysis of embryonic kidney from Ret(−/− mice, we found the upregulation of several FGFs, including FGF7. To examine the intracellular pathways, we then analyzed GDNF-dependent and GDNF-independent budding in the isolated WD culture. In both conditions, Akt activation was found to be important; however, whereas this occurred through PI3-kinase in GDNF-dependent budding, in the case of GDNF-independent budding, Akt activation was apparently via a PI3-kinase independent mechanism. Jnk signaling and the AP-1 transcription factor complex were also implicated in GDNF-independent budding. FosB, a binding partner of c-Jun in the formation of AP-1, was the most highly upregulated gene in the ret knockout kidney (in which budding had still occurred, and we found that its siRNA-mediated knockdown in isolated WDs also blocked GDNF-independent budding. Taken together with the finding that inhibition of Jnk signaling does not block Akt activation/phosphorylation in GDNF-independent budding, the data support necessary roles for both FosB/Jun/AP-1 signaling and PI3-kinase-independent activation of Akt in GDNF-independent budding. A model is proposed for signaling events that involve Akt and JNK working to regulate GDNF-independent WD budding.

  14. Puerarin attenuates carbon tetrachloride-induced liver oxidative stress and hyperlipidaemia in mouse by JNK/c-Jun/CYP7A1 pathway.

    Science.gov (United States)

    Ma, Jie-Qiong; Ding, Jie; Zhao, Hai; Liu, Chan-Min

    2014-11-01

    Puerarin (PU), a natural flavonoid, has been reported to have many benefits and medicinal properties. The aim of this study was to investigate the effects of puerarin on hepatic oxidative stress and hyperlipidaemia in mice exposed to carbon tetrachloride (CCl4). Male ICR mice were injected with CCl4 with or without puerarin co-administration (200 and 400 mg/kg intragastrically once-daily) for 8 weeks. Our data showed that puerarin significantly prevented CCl4-induced hepatotoxicity, indicated by both diagnostic indicators of the liver damage (serum aminotransferase levels) and histopathological analysis. Puerarin decreased the thiobarbituric acid reactive substances (TBARS) and the protein carbonyl content (PCO) in the liver of CCl4-treated mice. Puerarin also restored the levels of reduced glutathione (GSH) and total antioxidant capacity (TAC) in the liver. Furthermore, the increase in serum cholesterol, triglycerides and low-density lipoproteins (LDL) induced by CCl4 was effectively suppressed by puerarin. The high-density lipoprotein (HDL) level in the CCl4 treatment mice was also increased by puerarin. Western blot analysis showed that puerarin remarkably inhibited hyperlipidaemia by regulating the expression of phosphorylated Jun N-terminal kinases (JNK), phosphorylated c-Jun protein and cholesterol 7a-hydroxylase (CYP7A1) in the liver of CCl4-treated mice. Altogether, these results suggest that puerarin could protect the CCl4-induced liver injury and hyperlipidaemia by reducing reactive oxygen species S production, renewing the total antioxidant capacity and influencing expression of hepatic lipid biosynthesis and metabolism genes.

  15. Valoración económica del almacenamiento de agua y carbono en la comunidad campesina Villa de Junín

    Directory of Open Access Journals (Sweden)

    Miguel Vila Balbin

    2015-12-01

    Full Text Available El objetivo ha sido estimar el valor económico que generan los bofedales en el almacenamiento de agua y carbono en la comunidad campesina Villa de Junín en el departamento de Junín, Perú. El proceso de recolección de datos a estado enfocado en datos meteorológicos (temperatura y precipitación, datos de la actividad económica predominante (ganadería, recolección de muestras de suelo para hallar el contenido de carbono y capacidad volumétrica; posteriormente se hizo la comparación del beneficio percibido por la actividad ganadera y el beneficio que se podría obtener por los servicios que brinda un bofedal (almacenamiento de agua y carbono. Entre los resultados respecto a la precipitación anual se ha determinado 22 367 664 m3/año, del cual un 42,56 % (9 294 933,67 m3/ año regresa a la atmósfera a través del proceso de la evapotranspiración, quedando una oferta hídrica disponible de 13 072 730,33 m3/año, que representa un 57,44 % de la oferta hídrica total; la productividad hídrica es de 0,01 S/./m3. El costo de oportunidad que tiene la ganadería es de 200,38 S/./ha /año; el valor económico de agua y carbono es de S/. 48 974 181,79 y S/. 44 305 010,31 respectivamente. Se concluye que el almacenamiento de agua y carbono brindan mayores ingresos económicos a la población que la actividad ganadera.

  16. Momordica charantia polysaccharides could protect against cerebral ischemia/reperfusion injury through inhibiting oxidative stress mediated c-Jun N-terminal kinase 3 signaling pathway.

    Science.gov (United States)

    Gong, Juanjuan; Sun, Fumou; Li, Yihang; Zhou, Xiaoling; Duan, Zhenzhen; Duan, Fugang; Zhao, Lei; Chen, Hansen; Qi, Suhua; Shen, Jiangang

    2015-04-01

    Momordica charantia (MC) is a medicinal plant for stroke treatment in Traditional Chinese Medicine, but its active compounds and molecular targets are unknown yet. M. charantia polysaccharide (MCP) is one of the important bioactive components in MC. In the present study, we tested the hypothesis that MCP has neuroprotective effects against cerebral ischemia/reperfusion injury through scavenging superoxide (O2(-)), nitric oxide (NO) and peroxynitrite (ONOO(-)) and inhibiting c-Jun N-terminal protein kinase (JNK3) signaling cascades. We conducted experiments with in vivo global and focal cerebral ischemia/reperfusion rat models and in vitro oxygen glucose deprivation (OGD) neural cells. The effects of MCP on apoptotic cell death and infarction volume, the bioactivities of scavenging O2(-), NO and ONOO(-), inhibiting lipid peroxidation and modulating JNK3 signaling pathway were investigated. Major results are summarized as below: (1) MCP dose-dependently attenuated apoptotic cell death in neural cells under OGD condition in vitro and reduced infarction volume in ischemic brains in vivo; (2) MCP had directing scavenging effects on NO, O2(-) and ONOO(-) and inhibited lipid peroxidation; (3) MCP inhibited the activations of JNK3/c-Jun/Fas-L and JNK3/cytochrome C/caspases-3 signaling cascades in ischemic brains in vivo. Taken together, we conclude that MCP could be a promising neuroprotective ingredient of M. charantia and its mechanisms could be at least in part attributed to its antioxidant activities and inhibiting JNK3 signaling cascades during cerebral ischemia/reperfusion injury. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. c-Jun NH2-terminal kinase activity in subcutaneous adipose tissue but not nuclear factor-kappaB activity in peripheral blood mononuclear cells is an independent determinant of insulin resistance in healthy individuals

    DEFF Research Database (Denmark)

    Sourris, Karly C; Lyons, Jasmine G; de Courten, Maximilian

    2009-01-01

    Chronic low-grade activation of the immune system (CLAIS) predicts type 2 diabetes via a decrease in insulin sensitivity. Our study investigated potential relationships between nuclear factor-kappaB (NF-kappaB) and c-Jun NH(2)-terminal kinase (JNK) pathways-two pathways proposed as the link between...... CLAIS and insulin resistance....

  18. Growth arrest- and DNA-damage-inducible 45beta gene inhibits c-Jun N-terminal kinase and extracellular signal-regulated kinase and decreases IL-1beta-induced apoptosis in insulin-producing INS-1E cells

    DEFF Research Database (Denmark)

    Larsen, Claus Morten; Døssing, M G; Papa, S;

    2006-01-01

    IL-1beta is a candidate mediator of apoptotic beta cell destruction, a process that leads to type 1 diabetes and progression of type 2 diabetes. IL-1beta activates beta cell c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK) and p38, all of which are members of the mitogen...

  19. 原癌基因c-jun在毒胡萝卜素内酯诱导小鼠胚胎成纤维细胞凋亡中的作用%The role of c-jun in thapsigargin-induced mouse fibroblast cell apoptosis

    Institute of Scientific and Technical Information of China (English)

    张洁; 周方舟; 曹新冉; 任宏生; 楚玉峰; 王爱红; 董波; 赵鹏

    2016-01-01

    Objective To examine the impact of c-jun on thapsigargin-induced fibroblast cell apoptosis and address the mecha-nisms.Methods The thapsigargin was used to treat c-jun-/-mouse fibroblast cells,wild-type mouse fibroblasts and reconstitution of c-jun expression in c-jun-/-cells(c-jun Re).Cell viability was evaluated by trypan blue dye exclusion.Apoptosis was detected by fluorescence ac-tivated cell sorting(FACS)and DNA staining.c-jun,caspase-12,Grp78,Gadd153 and α-tubulin were analyzed by immunoblotting.Confocal images of cells loaded with the ER-Tracker and visualized by two-photon microscopy.Results Wild type(c-jun+/+),c-jun-/-and c-jun Re cells exhibited dramatic differences in sensitivity to TG.The c-jun-/-cells were the most sensitive,while c-jun Re cells were relatively resistant,to TG-induced cell death(P<0.05).TG treatment led to the activation of caspase-12,as indicated by the cleavage of procaspase-12, in c-jun-/-cells in a time-dependent manner.In contrast,caspase-12 activation was significantly attenuated in wild type fibroblast cells and abrogated in c-jun Re cells in response to TG treatment(P<0.05).c-jun-/-cells exhibited a large degree of apoptosis after treatment with TG,while c-jun Re cells demonstrated relative resistance to TG-induced apoptosis.c-jun-/-mouse fibroblast cells were more sensitive to TG-induced cell death compared to wild-type mouse fibroblasts,while reconstitution of c-jun expression in c-jun-/-cells(c-Jun Re)enhanced re-sistance to TG-induced cell death(P<0.05).The expression levels of ER chaperones Grp78 and Gadd153 induced by TG were lower in c-jun Re than those in c-jun-/-cells.ER-tracker found different patterns in the ER structure between c-jun-/-and c-jun Re cells.Conclusions Thapsigargin could cause mouse fibroblast cells apoptosis.c-jun gene expression changes of apoptosis degree,this change is mediated by endoplasmic reticulum stress.c-jun gene expression plays a protective role in thapsigargin-induced fibroblast cell

  20. The oncoprotein NPM-ALK of anaplastic large-cell lymphoma induces JUNB transcription via ERK1/2 and JunB translation via mTOR signaling.

    Science.gov (United States)

    Staber, Philipp B; Vesely, Paul; Haq, Naznin; Ott, Rene G; Funato, Kotaro; Bambach, Isabella; Fuchs, Claudia; Schauer, Silvia; Linkesch, Werner; Hrzenjak, Andelko; Dirks, Wilhelm G; Sexl, Veronika; Bergler, Helmut; Kadin, Marshall E; Sternberg, David W; Kenner, Lukas; Hoefler, Gerald

    2007-11-01

    Anaplastic large cell lymphomas (ALCLs) are highly proliferating tumors that commonly express the AP-1 transcription factor JunB. ALK fusions occur in approximately 50% of ALCLs, and among these, 80% have the t(2;5) translocation with NPM-ALK expression. We report greater activity of JunB in NPM-ALK-positive than in NPM-ALK-negative ALCLs. Specific knockdown of JUNB mRNA using small interfering RNA and small hairpin RNA in NPM-ALK-expressing cells decreases cellular proliferation as evidenced by a reduced cell count in the G2/M phase of the cell cycle. Expression of NPM-ALK results in ERK1/2 activation and transcriptional up-regulation of JUNB. Both NPM-ALK-positive and -negative ALCL tumors demonstrate active ERK1/2 signaling. In contrast to NPM-ALK-negative ALCL, the mTOR pathway is active in NPM-ALK-positive lymphomas. Pharmacological inhibition of mTOR in NPM-ALK-positive cells down-regulates JunB protein levels by shifting JUNB mRNA translation from large polysomes to monosomes and ribonucleic particles (RNPs), and decreases cellular proliferation. Thus, JunB is a critical target of mTOR and is translationally regulated in NPM-ALK-positive lymphomas. This is the first study demonstrating translational control of AP-1 transcription factors in human neoplasia. In conjunction with NPM-ALK, JunB enhances cell cycle progression and may therefore represent a therapeutic target.

  1. Simvastatin induces NFκB/p65 down-regulation and JNK1/c-Jun/ATF-2 activation, leading to matrix metalloproteinase-9 (MMP-9) but not MMP-2 down-regulation in human leukemia cells.

    Science.gov (United States)

    Chen, Ying-Jung; Chang, Long-Sen

    2014-12-15

    The aim of the present study was to explore the signaling pathways associated with the effect of simvastatin on matrix metalloproteinase-2 (MMP-2)/MMP-9 expression in human leukemia K562 cells. In sharp contrast to its insignificant effect on MMP-2, simvastatin down-regulated MMP-9 protein expression and mRNA levels in K562 cells. Simvastatin-induced Pin1 down-regulation evoked NFκB/p65 degradation. Meanwhile, simvastatin induced JNK-mediated c-Jun and ATF-2 activation. Over-expression of Pin1 suppressed simvastatin-induced MMP-9 down-regulation. Treatment with SP600125 (a JNK inhibitor) or knock-down of JNK1 reduced MMP-2 expression in simvastatin-treated cells. Simvastatin enhanced the binding of c-Jun/ATF-2 with the MMP-2 promoter. Down-regulation of c-Jun or ATF-2 by siRNA revealed that c-Jun/ATF-2 activation was crucial for MMP-2 expression. Suppression of p65 activation or knock-down of Pin1 by shRNA reduced MMP-2 and MMP-9 expression in K562 cells. Over-expression of constitutively active JNK1 rescued MMP-2 expression in Pin1 shRNA-transfected cells. Simvastatin treatment also suppressed MMP-9 but not MMP-2 expression in human leukemia U937 and KU812 cells. Taken together, our data indicate that simvastatin-induced p65 instability leads to MMP-9 down-regulation in leukemia cells, while simvastatin-induced JNK1/c-Jun/ATF-2 activation maintains the MMP-2 expression underlying p65 down-regulation. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Significant efficiency findings while controlling for the frequent confounders of CAI research in the PlanAlyzer project's computer-based, self-paced, case-based programs in anemia and chest pain diagnosis.

    Science.gov (United States)

    Lyon, H C; Healy, J C; Bell, J R; O'Donnell, J F; Shultz, E K; Wigton, R S; Hirai, F; Beck, J R

    1991-04-01

    Richard E. Clark in his widely published comprehensive studies and meta-analyses of the literature on computer assisted instruction (CAI) has decried the lack of carefully controlled research, challenging almost every study which shows the computer-based intervention to result in significant post-test proficiency gains over a non-computer-based intervention. We report on a randomized study in a medical school setting where the usual confounders found by Clark to plague most research, were carefully controlled. PlanAlyzer is a microcomputer-based, self-paced, case-based, event-driven system for medical education which was developed and used in carefully controlled trials in a second year medical school curriculum to test the hypothesis that students with access to the interactive programs could integrate their didactic knowledge more effectively and/or efficiently than with access only to traditional textual "nonintelligent" materials. PlanAlyzer presents cases, elicits and critiques a student's approach to the diagnosis of two common medical disorders: anemias and chest pain. PlanAlyzer uses text, hypertext, images and critiquing theory. Students were randomized, one half becoming the experimental group who received the interactive PlanAlyzer cases in anemia, the other half becoming the controls who received the exact same content material in a text format. Later in each year there was a crossover, the controls becoming the experimentals for a similar intervention with the cardiology PlanAlyzer cases. Preliminary results at the end of the first two full trials shows that the programs have achieved most of the proposed instructional objectives, plus some significant efficiency and economy gains. 96 faculty hours of classroom time were saved by using PlanAlyzer in their place, while maintaining high student achievement. In terms of student proficiency and efficiency, the 328 students in the trials over two years were able to accomplish the project's instructional

  3. Telmisartan directly ameliorates the neuronal inflammatory response to IL-1β partly through the JNK/c-Jun and NADPH oxidase pathways

    Science.gov (United States)

    2012-01-01

    Background Blockade of angiotensin II type 1 (AT1) receptors ameliorates brain inflammation, and reduces excessive brain interleukin-1 beta (IL-1β) production and release from cortical microglia. The aim of this study was to determine whether, in addition, AT1 receptor blockade directly attenuates IL-1β-induced inflammatory responses in neuronal cultures. Methods SK-N-SH human neuroblasts and primary rat cortical neurons were pretreated with telmisartan followed by exposure to IL-1β. Gene expression was determined by reverse transcriptase (RT)-PCR, protein expression and kinase activation by western blotting, NADPH oxidase activity by the lucigenin method, prostaglandin E2 (PGE2) release by enzyme immunoassay, reactive oxygen species (ROS) generation by the dichlorodihydrofluorescein diacetate fluorescent probe assay, and peroxisome proliferator-activated receptor gamma (PPARγ) involvement was assessed with the antagonists GW9662 and T0070907, the agonist pioglitazone and the expression of PPARγ target genes ABCG1 and CD36. Results We found that SK-N-SH neuroblasts expressed AT1 but not AT2 receptor mRNA. Telmisartan reduced IL-1β-induced cyclooxygenase-2 (COX-2) expression and PGE2 release more potently than did candesartan and losartan. Telmisartan reduced the IL-1β-induced increase in IL-1R1 receptor and NADPH oxidase-4 (NOX-4) mRNA expression, NADPH oxidase activity, and ROS generation, and reduced hydrogen peroxide-induced COX-2 gene expression. Telmisartan did not modify IL-1β-induced ERK1/2 and p38 mitogen-activated protein kinase (MAPK) phosphorylation or nuclear factor-κB activation but significantly decreased IL-1β-induced c-Jun N-terminal kinase (JNK) and c-Jun activation. The JNK inhibitor SP600125 decreased IL-1β-induced PGE2 release with a potency similar to that of telmisartan. The PPARγ agonist pioglitazone reduced IL-1β-induced inflammatory reaction, whereas telmisartan did not activate PPARγ, as shown by its failure to enhance the

  4. Ofidismo en la provincia de Chanchamayo, Junín: revisión de 170 casos consecutivos en el Hospital de Apoyo de La Merced

    Directory of Open Access Journals (Sweden)

    Miguel Villanueva Forero

    2004-04-01

    Full Text Available Objetivo: Describir las características clínico-epidemiológicas del ofidismo en la provincia de Chanchamayo, Junín, Perú. Materiales y métodos: Se revisaron todas las historias clínicas de pacientes con diagnóstico de ofidismo en el "Hospital de Apoyo de La Merced" (HALM, Junín, Perú entre enero de 1998 y diciembre del 2000. Se recogieron datos de demográficos y clínico-epidemiológicos. Resultados: Las historias clínicas revisadas fueron 195, de estas, 170 fueron incluidas en el análisis. La media edad fue 26.2 años (rango: 1-76 años. La mayoría (62.4% era de sexo masculino. El 43.5% provenía del distrito de La Merced. Los casos de ofidismo ocurrieron con mayor frecuencia (67% durante los meses de lluvia (de diciembre a mayo. La localización más frecuente de la mordedura fue en los miembros inferiores (67.7%. El tiempo entre el accidente y la atención médica fue en promedio de 5 hrs. 43 min. (± 5 hrs. 56 min.. El animal agresor se identificó en 37.6% de las veces, siendo el más frecuente el Bothrops atrox (36.5%. Los síntomas más comunes que acompañaron el cuadro clínico fueron dolor, edema, eritema (80%. La mayoría (78.3% recibió suero antiofídico, de estos, 18.8% presentaron reacciones anafilactoides o urticariformes luego de la administración. La complicación más frecuente fue celulitis, presentándose mas comúnmente en pacientes que recibieron corticoides por más de 5 días (p=0.024. Ningún paciente falleció. Conclusiones: La mayoría de accidentes ofídicos en esta región ocurren en el ámbito rural. La utilización de corticoides por más de 5 días se asoció con una mayor frecuencia de celulitis. Las reacciones de hipersensibilidad hacia el suero antiofídico no son raras, siendo recomendable realizar la prueba intradérmica antes de su administración. (Rev Med Hered 2004; 15: 82-87.

  5. 古典戏曲学“俊语”术语纵论%Terms of “jun yu” in Classical and Traditional Operas

    Institute of Scientific and Technical Information of China (English)

    胡俊国; 张小芳

    2015-01-01

    In the classical and traditional operas, the term of “jun yu” in criticism has transformed from the definition of drama literary style to one of the names of genres. It reflects the classical changes of traditional operas from the civic skills to the elegant interest of literary men and its self-adaptation ability and consciousness. To keep up with the perceptual characteristics of traditional criticism, based on the “secondary”writing practice and combining with the theory of literature, we can outline the connotation of “jun yu”, inspect the change of positions of criticism term in the theoretical system and analyze its theoretical va-lidity and value in the context of different times. Then we can achieve the pulse of theoretical development and acquire the liter-ary and aesthetic interests and the specific problems from different perspectives.%古典戏曲学中“俊语”这一批评术语,经历了从作为戏曲文学语体本质特征的界定,到用作语体之一的称名,体现了古典戏曲学面对创作实践从市井机巧到文人雅趣的变化,以及进行自我调适的能力和意识。顺应传统批评方式的感性特质,以对创作实践的“二次”品鉴为基础,与理论文献相印证,对“俊语”术语内涵层次和纵向发展轨迹加以勾勒,考察批评术语在理论体系中的地位变迁,分析其在不同时代语境中理论效度和价值生命,可以达到对理论史发展脉搏的把握,获得对其时文学审美趣向及其面临的具体问题的别样认知视角。

  6. Response to the Comment by S.B. Simon, L. Grossman, and S.R. Sutton on "Valence state of titanium in the Wark-Lovering rim of a Leoville CAI as a record of progressive oxidation in the early Solar Nebula"

    Science.gov (United States)

    Young, Edward D.; Dyl, Kathryn A.; Simon, Justin I.

    2012-05-01

    S. Simon et al. incorrectly suggest that in earlier work we claimed there was no Ti3+ in Wark-Lovering rim pyroxenes. In neither the paper by Simon et al. (2005) nor the subsequent paper by Dyl et al. (2011) did we assert that there was no Ti3+ in rim pyroxenes. Rather, we found that many pyroxenes have Ti3+ below detection while others have lower Ti3+/Ti4+ than is typical of CAI interiors, indicating rim formation in a relatively oxidizing environment. Dyl et al. (2011) showed through exhaustive testing that the suggestion by Simon et al. (2007) that EMPA data in the paper by Simon et al. (2005) were flawed is incorrect. Here we consider each point raised in the comment by S. Simon et al. and reiterate that our electron microprobe data and the XANES data of Simon et al. (2007) agree and demonstrate a statistically significant (˜2σ) or greater difference between rim and interior pyroxene Ti3+/Ti4+. We show that the oxidation states of Ti in Wark-Lovering rim pyroxenes, the chemistry of rim pyroxenes, and the modal abundances of rim minerals are best explained by reaction between the CAI and gas that was orders of magnitude more oxidizing than the solar-like gas from which the CAIs originally formed.

  7. A cold metal poor cloud traced by a weak MgII absorption at z~0.45. First detection of SiI, CaI and FeI in a QSO absorber

    CERN Document Server

    D'Odorico, Valentina

    2007-01-01

    We present the observations of a weak MgII absorption system detected at z~0.452 in the UVES high resolution spectrum of the QSO HE0001-2340. The weakest of the two MgII components forming the system shows associated absorptions due to SiI, CaI and FeI observed for the first time in a QSO spectrum. We investigate the nature of this absorber by comparing its properties with those of different classes of absorbers (weak MgII, Damped Ly-alpha systems and local interstellar clouds) and reproducing its ionization conditions with photoionization models. The observed absorber belongs to the class of weak MgII systems on the basis of its equivalent width, however the relative strength of commonly observed transitions deviates significantly from those of the above mentioned absorbers. A rough estimate of the probability to cross such a system with a QSO line of sight is P~0.03. The presence of rare neutral transitions suggests that the cloud is shielded by a large amount of neutral Hydrogen. A detailed comparison of t...

  8. 蔡元培音乐美育思想主要内涵及其具体实践%The Main Connotation and Concrete Practice of Cai Yuanpei's Music Education Thoughts

    Institute of Scientific and Technical Information of China (English)

    李作方

    2014-01-01

    蔡元培先生是我国近代音乐教育的积极提倡者和实践者,其音乐美育思想主要内涵包括:以提高国民素质为目标的普及音乐思想,东西方音乐融合创新思想,重视挖掘民族传统音乐思想,重视音乐美育的社会作用思想等。同时他注重身体力行,在北京大学等地实践其音乐美育教育的思想。%Cai Yuanpei is an active advocate and practitioner of music education in modern China. The main connotations of his music education thoughts include:massive music education with the purpose to raise people's qualities,creative music in the west and the east,traditional national music and emphasis on social function of music education. In the mean time,he focused on pactice,and carried out music education in Peking University.

  9. Sino-Vietnamese Cultural Exchanges from the Cai Tinglan's Book%从蔡廷兰的《海南杂著》看中越文化交流

    Institute of Scientific and Technical Information of China (English)

    谢小兰; 滕兰花

    2012-01-01

    Cai Tinglan's book, Miscellaneous Work on Hai Nan, about Sino-Vietnamese cultural exchanges, recorded the Sino-Vietnamese trading situation, widely used Chinese characters in Vietnam, the same God worship and Vietnamese political systems affected by China's, which are the significant historical materials for the study of China-Vietnamese relations.%1835年,中国澎湖籍的儒生蔡廷兰自厦门乘船返乡时遇险,被风吹到越南中部,他写成的《海南杂著》如实记录了他在越南的所见所闻。书中不仅记录了越南深受中国的政治制度影响,还记录了中越两国的经济贸易情况,并且把中越两国的文化交流如汉字在越南的广泛被使用、共同的神灵崇拜等,这些都成为人们研究清中后期中越关系史的重要史料。

  10. 蔡元培公民道德教育思想及其启示%Cai Yuan-pei's Ideas of Civic Moral Education and the Implications

    Institute of Scientific and Technical Information of China (English)

    寇婷

    2012-01-01

    蔡元培公民道德教育思想的内核是儒家“修身、齐家、治国、平天下”和西方“民主、平等、博爱”思想相结合,自律与他律相统一,理性与诗性兼备。其启示有三:公民权利意识教育是实现公民教育的前提;法治教育是现代公民教育的基本内容;适当的公民教育方法是保障公民教育有效实施的重要途径。%The core of Cai Yuanpei's ideas of civic and moral education is a combination ot ContucLan "selfcultivation, regulating the family, managing the state and world affairs" and the Western "de mocracy, equality, and fraternity" of selfdiscipline and heteronomy, and of rationalism and romanti cism. The implications include the civil rights awareness is the premise of civic education legal edu cation is the basic content of modern civic education; appropriate civic education is an important way of effective implementation of the civic education.

  11. Using director to design CAI courseware%利用Director软件制作CAI课件 ——“多媒体组合教学设计理论与实践”CAI课件的实现

    Institute of Scientific and Technical Information of China (English)

    王满华

    2001-01-01

    如何提高多媒体组合教学的质量和效果,是当前教师在多媒体组合教学活动中面临的重要课题.为使广大教师能更快地掌握多媒体组合教学设计的理论,吸收现有的多媒体组合教学实践经验,设计制作了“多媒体组合教学设计理论与实践”的CAI课件,并着重介绍了该课件的设计与制作过程.%The important task which teachers are confronted with is how to improve didactical qualities and effects in the multimedia combined teaching activities. In order to help teachers grasping the theories of design and absorbing experiences of practice, the author has produced an CAI courseware,the theories and the practices in the multimedia combined teaching design. This paper introduces it′s processes in designing and producing.

  12. Correlated expression of glutathione S-transferase-{pi} and c-Jun or other oncogene products in human squamous cell carcinomas of the head and neck. Relevance to relapse after radiation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Miura, Kohki; Suzuki, Shinsaku; Tanita, Jiro; Shinkawa, Hideichi; Satoh, Kimihiko; Tsuchida, Shigeki [Hirosaki Univ., Aomori (Japan). School of Medicine

    1997-02-01

    The expression of glutathione S-transferase (GST)-{pi} and four oncogene products, c-Jun, c-Fos, c-H-Ras, and c-Myc, in human squamous cell carcinomas of the head and neck was investigated immunohistochemically before and after radiation therapy, to examine whether these oncogene products might be involved in GST-{pi} expression, and also to examine the relationship between their expression and therapeutic response. Clinical response to radiation was evaluated in terms of both tumor regression and relapse over two-year follow-up periods. The overall positive rates in 83 carcinoma specimens before therapy were 60.2% for GST-{pi} and 28.9-51.8% for the individual oncogene products, the positive rates for the oncogene products being higher in GST-{pi}-positive than in GST-{pi}-negative cancers. c-Jun was most highly correlated with GST-{pi} expression. Following radiation, the expression of GST-{pi} and the oncogene products was altered in about a half of 30 patients. Eleven of the 18 patients who exhibited prior positivity for GST-{pi} showed negative conversion, while 4 of the 12 patients with prior negativity demonstrated positive conversion. In most cases, changes in c-Jun staining coincided with those in GST-{pi}. Regarding clinical response to radiation therapy, the positive rates for GST-{pi} and c-Jun before radiation were higher in the residual cancer or relapse cases than in the group showing complete response without relapse. Examination of 26 patients with laryngeal cancer revealed that relapse occurred more frequently in cases exhibiting positive reactions for GST-{pi}, c-Jun, or c-H-Ras. These results suggest a direct link between c-Jun and GST-{pi} in head and neck cancers before and after radiation. Although GST-{pi} and the oncogene products can be influenced by radiation, GST-{pi} and c-H-Ras expression may be a risk factor for relapse of laryngeal cancer. (author)

  13. A comparative study of fibrous dysplasia and osteofibrous dysplasia with regard to expressions of c-fos and c-jun products and bone matrix proteins: a clinicopathologic review and immunohistochemical study of c-fos, c-jun, type I collagen, osteonectin, osteopontin, and osteocalcin.

    Science.gov (United States)

    Sakamoto, A; Oda, Y; Iwamoto, Y; Tsuneyoshi, M

    1999-12-01

    Fibrous dysplasia and osteofibrous dysplasia are both benign fibro-osseous lesions of the bone and are generally seen during childhood or adolescence. Histologically, the features of these bone lesions sometimes look quite similar, but their precise nature remains controversial. We retrospectively studied clinicopathologic findings in 62 cases of fibrous dysplasia and 20 cases of osteofibrous dysplasia with regard to their anatomic location and histological appearance. From among these cases, the immunohistochemical expressions of c-fos and c-jun proto-oncogene products and bone matrix proteins of type I collagen, osteonectin, osteopontin, and osteocalcin were evaluated in 20 typical fibrous dysplasias and 17 osteofibrous dysplasias using paraffin sections, and these expressions were then assessed semiquantitatively. Microscopically, fibrous dysplasia showed various secondary changes, such as hyalinization, hemorrhage, xanthomatous reaction, and cystic change in 22 of the 62 cases (35%). This was a higher incidence than in osteofibrous dysplasia, in which only 2 of the 20 cases (10%) showed such changes. In the elderly fibrous dysplasia cases, the cellularity of fibroblast-like cells was rather low, and those cases were hyalinized. Almost all of the cases of fibrous dysplasia and osteofibrous dysplasia showed positive expressions of c-fos and c-jun products. The expressions of type I collagen and osteopontin showed no difference between fibrous dysplasia and osteofibrous dysplasia. Immunoreactivity for osteonectin in bone matrix was detected in only 1 case of fibrous dysplasia (1 of 20), whereas it was recognized in 14 of the 17 cases of osteofibrous dysplasia. Furthermore, the immunoreactivity for osteocalcin in bone matrix and fibroblast-like cells was higher in fibrous dysplasia than it was in osteofibrous dysplasia, semiquantitatively. Our immunohistochemical results regarding osteonectin and osteocalcin suggest that the bone matrix of fibrous dysplasia is

  14. Inhibition of development of experimental abdominal aortic aneurysm by c-jun N-terminal protein kinase inhibitor combined with lysyl oxidase gene modified smooth muscle progenitor cells.

    Science.gov (United States)

    Chen, Feng; Zhang, ZhenDong; Zhu, XianHua

    2015-11-05

    Chronic inflammation, imbalance between the extracellular matrix synthesis and degradation, and loss of vascular smooth muscle cells (SMCs) contribute to the development of abdominal aortic aneurysm (AAA). The purpose of this study was to investigate the effect of the therapy with periaortic incubation of c-Jun N-terminal protein kinase inhibitor SP600125 infused from an osmotic pump and subadventitial injection of lysyl oxidase (LOX) gene modified autologous smooth muscle progenitor cells (SPCs) on treatment of AAA in a rabbit model. Obvious dilation of the abdominal aorta in the control group was caused by periaortic incubation of calcium chloride and elastase. But the progression of aortic dilation was significantly decreased after the treatment with SP600125 and LOX gene modified SPCs compared to the treatment with phosphate-buffered saline. This therapy could inhibit matrix metalloproteinases expression, enhance elastin synthesis, improve preservation of elastic laminar integrity, benefit SPCs survival and restore SMCs population. It seemed that this method might provide a novel therapeutic strategy to treat AAA.

  15. Tolerance to the antinociceptive and hypothermic effects of morphine is mediated by multiple isoforms of c-Jun N-terminal kinase.

    Science.gov (United States)

    Yuill, Matthew B; Zee, Michael L; Marcus, David; Morgan, Daniel J

    2016-04-13

    The abuse and overdose of opioid drugs are growing public health problems worldwide. Although progress has been made toward understanding the mechanisms governing tolerance to opioids, the exact cellular machinery involved remains unclear. However, there is growing evidence to suggest that c-Jun N-terminal kinases (JNKs) play a major role in mu-opioid receptor regulation and morphine tolerance. In this study, we aimed to determine the potential roles of different JNK isoforms in the development of tolerance to the antinociceptive and hypothermic effects of morphine. We used the hot-plate and tail-flick tests for thermal pain to measure tolerance to the antinociceptive effects of once-daily subcutaneous injections with 10 mg/kg morphine. Body temperature was also measured to determine tolerance to the hypothermic effects of morphine. Tolerance to morphine was assessed in wild-type mice and compared with single knockout mice each lacking the JNK isoforms (JNK1, JNK2, or JNK3). We found that loss of each individual JNK isoform causes impairment in tolerance for the antinociceptive and hypothermic effects of daily morphine. However, disruption of JNK2 seems to have the most profound effect on morphine tolerance. These results indicate a clear role for JNK signaling pathways in morphine tolerance. This complements previous studies suggesting that the JNK2 isoform is required for morphine tolerance, but additionally presents novel data suggesting that additional JNK isoforms also contribute toward this process.

  16. Effects of c-Jun N-terminal kinase on Activin A/Smads signaling in PC12 cell suffered from oxygen-glucose deprivation.

    Science.gov (United States)

    Wang, J Q; Xu, Z H; Liang, W Z; He, J T; Cui, Y; Liu, H Y; Xue, L X; Shi, W; Shao, Y K; Mang, J; Xu, Z X

    2016-02-29

    Activin A (Act A), a member of transforming growth factor-β (TGF-β) superfamily, is an early gene in response to cerebral ischemia. Growing evidences confirm the neuroprotective effect of Act A in ischemic injury through Act A/Smads signal activation. In this process, regulation networks are involved in modulating the outcomes of Smads signaling. Among these regulators, crosstalk between c-Jun N-terminal kinase (JNK) and Smads signaling has been found in the TGF-β induced epithelial-mesenchymal transition. However, in neural ischemia, the speculative regulation between JNK and Act A/Smads signaling pathways has not been clarified. To explore this issue, an Oxygen Glucose Deprivation (OGD) model was introduced to nerve-like PC12 cells. We found that JNK signal activation occurred at the early time of OGD injury (1 h). Act A administration suppressed JNK phosphorylation. In addition, JNK inhibition could elevate the strength of Smads signaling and attenuate neural apoptosis after OGD injury. Our results indicated a negative regulation effect of JNK on Smads signaling in ischemic injury. Taken together, JNK, as a critical site for neural apoptosis and negative regulator for Act A/Smads signaling, was presumed to be a molecular therapeutic target for ischemia.

  17. TAp73-mediated the activation of c-Jun N-terminal kinase enhances cellular chemosensitivity to cisplatin in ovarian cancer cells.

    Directory of Open Access Journals (Sweden)

    Pingde Zhang

    Full Text Available P73, one member of the tumor suppressor p53 family, shares highly structural and functional similarity to p53. Like p53, the transcriptionally active TAp73 can mediate cellular response to chemotherapeutic agents in human cancer cells by up-regulating the expressions of its pro-apoptotic target genes such as PUMA, Bax, NOXA. Here, we demonstrated a novel molecular mechanism for TAp73-mediated apoptosis in response to cisplatin in ovarian cancer cells, and that was irrespective of p53 status. We found that TAp73 acted as an activator of the c-Jun N-terminal kinase (JNK signaling pathway by up-regulating the expression of its target growth arrest and DNA-damage-inducible protein GADD45 alpha (GADD45α and subsequently activating mitogen-activated protein kinase kinase-4 (MKK4. Inhibition of JNK activity by a specific inhibitor or small interfering RNA (siRNA significantly abrogated TAp73-mediated apoptosis induced by cisplatin. Furthermore, inhibition of GADD45α by siRNA inactivated MKK4/JNK activities and also blocked TAp73-mediated apoptosis induction by cisplatin. Our study has demonstrated that TAp73 activated the JNK apoptotic signaling pathway in response to cisplatin in ovarian cancer cells.

  18. Systematic analysis of BRAF(V600E) melanomas reveals a role for JNK/c-Jun pathway in adaptive resistance to drug-induced apoptosis.

    Science.gov (United States)

    Fallahi-Sichani, Mohammad; Moerke, Nathan J; Niepel, Mario; Zhang, Tinghu; Gray, Nathanael S; Sorger, Peter K

    2015-03-26

    Drugs that inhibit RAF/MEK signaling, such as vemurafenib, elicit profound but often temporary anti-tumor responses in patients with BRAF(V) (600E) melanoma. Adaptive responses to RAF/MEK inhibition occur on a timescale of hours to days, involve homeostatic responses that reactivate MAP kinase signaling and compensatory mitogenic pathways, and attenuate the anti-tumor effects of RAF/MEK inhibitors. We profile adaptive responses across a panel of melanoma cell lines using multiplex biochemical measurement, single-cell assays, and statistical modeling and show that adaptation involves at least six signaling cascades that act to reduce drug potency (IC50) and maximal effect (i.e., Emax ≪ 1). Among these cascades, we identify a role for JNK/c-Jun signaling in vemurafenib adaptation and show that RAF and JNK inhibitors synergize in cell killing. This arises because JNK inhibition prevents a subset of cells in a cycling population from becoming quiescent upon vemurafenib treatment, thereby reducing drug Emax. Our findings demonstrate the breadth and diversity of adaptive responses to RAF/MEK inhibition and a means to identify which steps in a signaling cascade are most predictive of phenotypic response.

  19. Protective Effect of Lupeol Against Lipopolysaccharide-Induced Neuroinflammation via the p38/c-Jun N-Terminal Kinase Pathway in the Adult Mouse Brain.

    Science.gov (United States)

    Badshah, Haroon; Ali, Tahir; Shafiq-ur Rehman; Faiz-ul Amin; Ullah, Faheem; Kim, Tae Hyun; Kim, Myeong Ok

    2016-03-01

    Recent studies have demonstrated a close interaction between neuroinflammatory responses, increased production of inflammatory mediators, and neurodegeneration. Pathological findings in neurological diseases such as Alzheimer's disease, Parkinson's disease, and Huntington's disease have shown common signs of neuroinflammation and neurodegeneration. Lupeol, a natural pentacyclic triterpene, has revealed a number of pharmacological properties including an anti-inflammatory activity. This study aimed to evaluate the effect of lupeol against lipopolysaccharide (LPS)-induced neuroinflammation in the cortex and hippocampus of adult mice. Our results showed that systemic administration of LPS induced glial cell production of proinflammatory cytokines, tumor necrosis factor (TNF)-α, inducible nitric oxide synthase (iNOS), and interleukin (IL)-1β, while co-treatment with lupeol significantly inhibited the LPS-induced activation of microglia and astrocytes, and decreased the LPS-induced generation of TNF-α, iNOS, and IL-1β. The intracellular mechanism involved in the LPS-induced activation of inflammatory responses includes phosphorylation of P38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK), which was significantly inhibited by lupeol. We further elucidated that lupeol inhibited the LPS-induced activation of the mitochondrial apoptotic pathway and reversed the LPS-induced expression of apoptotic markers such as Bax, cytochrome C, caspase-9, and caspase-3. Taken together; our results suggest that lupeol inhibits LPS-induced microglial neuroinflammation via the P38-MAPK and JNK pathways and has therapeutic potential to treat various neuroinflammatory disorders.

  20. Pharmacological Inhibition of c-Jun N-terminal Kinase Reduces Food Intake and Sensitizes Leptin’s Anorectic Signaling Actions

    Science.gov (United States)

    Gao, Su; Howard, Shannon; LoGrasso, Philip V.

    2017-01-01

    The role for c-Jun N-terminal Kinase (JNK) in the control of feeding and energy balance is not well understood. Here, by use of novel and highly selective JNK inhibitors, we investigated the actions of JNK in the control of feeding and body weight homeostasis. In lean mice, intraperitoneal (i.p.) or intracerebroventricular (i.c.v.) administration of SR-3306, a brain-penetrant and selective pan-JNK (JNK1/2/3) inhibitor, reduced food intake and body weight. Moreover, i.p. and i.c.v. administrations of SR11935, a brain-penetrant and JNK2/3 isoform-selective inhibitor, exerted similar anorectic effects as SR3306, which suggests JNK2 or JNK3 mediates aspect of the anorectic effect by pan-JNK inhibition. Furthermore, daily i.p. injection of SR3306 (7 days) prevented the increases in food intake and weight gain in lean mice upon high-fat diet feeding, and this injection paradigm reduced high-fat intake and obesity in diet-induced obese (DIO) mice. In the DIO mice, JNK inhibition sensitized leptin’s anorectic effect, and enhanced leptin-induced STAT3 activation in the hypothalamus. The underlying mechanisms likely involve the downregulation of SOCS3 by JNK inhibition. Collectively, our data suggest that JNK activity promotes positive energy balance, and the therapeutic intervention inhibiting JNK activities represents a promising approach to ameliorate diet-induced obesity and leptin resistance. PMID:28165482

  1. c-Jun N-terminal kinase phosphorylation of MARCKSL1 determines actin stability and migration in neurons and in cancer cells.

    Science.gov (United States)

    Björkblom, Benny; Padzik, Artur; Mohammad, Hasan; Westerlund, Nina; Komulainen, Emilia; Hollos, Patrik; Parviainen, Lotta; Papageorgiou, Anastassios C; Iljin, Kristiina; Kallioniemi, Olli; Kallajoki, Markku; Courtney, Michael J; Mågård, Mats; James, Peter; Coffey, Eleanor T

    2012-09-01

    Cell migration is a fundamental biological function, critical during development and regeneration, whereas deregulated migration underlies neurological birth defects and cancer metastasis. MARCKS-like protein 1 (MARCKSL1) is widely expressed in nervous tissue, where, like Jun N-terminal protein kinase (JNK), it is required for neural tube formation, though the mechanism is unknown. Here we show that MARCKSL1 is directly phosphorylated by JNK on C-terminal residues (S120, T148, and T183). This phosphorylation enables MARCKSL1 to bundle and stabilize F-actin, increase filopodium numbers and dynamics, and retard migration in neurons. Conversely, when MARCKSL1 phosphorylation is inhibited, actin mobility increases and filopodium formation is compromised whereas lamellipodium formation is enhanced, as is cell migration. We find that MARCKSL1 mRNA is upregulated in a broad range of cancer types and that MARCKSL1 protein is strongly induced in primary prostate carcinomas. Gene knockdown in prostate cancer cells or in neurons reveals a critical role for MARCKSL1 in migration that is dependent on the phosphorylation state; phosphomimetic MARCKSL1 (MARCKSL1(S120D,T148D,T183D)) inhibits whereas dephospho-MARCKSL1(S120A,T148A,T183A) induces migration. In summary, these data show that JNK phosphorylation of MARCKSL1 regulates actin homeostasis, filopodium and lamellipodium formation, and neuronal migration under physiological conditions and that, when ectopically expressed in prostate cancer cells, MARCKSL1 again determines cell movement.

  2. Transcriptional activity of neural retina leucine zipper (Nrl) is regulated by c-Jun N-terminal kinase and Tip60 during retina development.

    Science.gov (United States)

    Kim, Jung-Woong; Jang, Sang-Min; Kim, Chul-Hong; An, Joo-Hee; Choi, Kyung-Hee

    2012-05-01

    Neural retina leucine zipper (Nrl), a key basic motif leucine zipper (bZIP) transcription factor, modulates rod photoreceptor differentiation by activating rod-specific target genes. In searching for factors that might couple with Nrl to modulate its transcriptional activity through posttranslational modification, we observed the novel interactions of Nrl with c-Jun N-terminal kinase 1 (JNK1) and HIV Tat-interacting protein 60 (Tip60). JNK1 directly interacted with and phosphorylated Nrl at serine 50, which enhanced Nrl transcriptional activity on the rhodopsin and Ppp2r5c promoters. Use of an inactive JNK1 mutant or treatment with a JNK inhibitor (SP600125) significantly reduced JNK1-mediated phosphorylation and transcriptional activity of Nrl in cultured retinal explants. We also found that Nrl activated rhodopsin and Ppp2r5c transcription by recruiting Tip60 to promote histone H3/H4 acetylation. The binding affinity of phospho-Nrl for Tip60 was significantly greater than that of the unphosphorylated Nrl. Thus, the histone acetyltransferase-containing Tip60 behaved as a coactivator in the Nrl-dependent transcriptional regulation of the rhodopsin and Ppp2r5c genes in the developing mouse retina. A transcriptional network of interactive proteins, including Nrl, JNK1, and Tip60, may be required to precisely control spatiotemporal photoreceptor-specific gene expression during retinal development.

  3. The Caenorhabditis elegans Ste20-related kinase and Rac-type small GTPase regulate the c-Jun N-terminal kinase signaling pathway mediating the stress response.

    Science.gov (United States)

    Fujiki, Kota; Mizuno, Tomoaki; Hisamoto, Naoki; Matsumoto, Kunihiro

    2010-02-01

    Mitogen-activated protein kinases (MAPKs) are integral to the mechanisms by which cells respond to physiological stimuli and a wide variety of environmental stresses. In Caenorhabditis elegans, the stress response is controlled by a c-Jun N-terminal kinase (JNK)-like MAPK signaling pathway, which is regulated by MLK-1 MAPK kinase kinase (MAPKKK), MEK-1 MAPKK, and KGB-1 JNK-like MAPK. In this study, we identify the max-2 gene encoding a C. elegans Ste20-related protein kinase as a component functioning upstream of the MLK-1-MEK-1-KGB-1 pathway. The max-2 loss-of-function mutation is defective in activation of KGB-1, resulting in hypersensitivity to heavy metals. Biochemical analysis reveals that MAX-2 activates MLK-1 through direct phosphorylation of a specific residue in the activation loop of the MLK-1 kinase domain. Our genetic data presented here also show that MIG-2 small GTPase functions upstream of MAX-2 in the KGB-1 pathway. These results suggest that MAX-2 and MIG-2 play a crucial role in mediating the heavy metal stress response regulated by the KGB-1 pathway.

  4. The phosphatidylinositol 3-kinase/Akt and c-Jun N-terminal kinase signaling in cancer: Alliance or contradiction? (Review).

    Science.gov (United States)

    Zhao, Hua-Fu; Wang, Jing; Tony To, Shing-Shun

    2015-08-01

    The phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway and c-Jun N-terminal kinase (JNK) pathway are responsible for regulating a variety of cellular processes including cell growth, migration, invasion and apoptosis. These two pathways are essential to the development and progression of tumors. The dual roles of JNK signaling in apoptosis and tumor development determine the different interactions between the PI3K/Akt and JNK pathways. Activation of PI3K/Akt signaling can inhibit stress- and cytokine-induced JNK activation through Akt antagonizing and the formation of the JIP1-JNK module, as well as the activities of upstream kinases ASK1, MKK4/7 and MLK. On the other hand, hyperactivation of Akt and JNK is also found in cancers that harbor EGFR overexpression or loss of PTEN. Understanding the activation mechanism of PI3K/Akt and JNK pathways, as well as the interplays between these two pathways in cancer may contribute to the identification of novel therapeutic targets. In the present report, we summarized the current understanding of the PI3K/Akt and JNK signaling networks, as well as their biological roles in cancers. In addition, the interactions and regulatory network between PI3K/Akt and JNK pathways in cancer were discussed.

  5. Role of Jun N-terminal Kinase (JNK) signaling in the wound healing and regeneration of a Drosophila melanogaster wing imaginal disc.

    Science.gov (United States)

    Mattila, Jaakko; Omelyanchuk, Leonid; Kyttälä, Satu; Turunen, Heikki; Nokkala, Seppo

    2005-01-01

    When a fragment of a Drosophila imaginal disc is cultured in growth permissive conditions, it either regenerates the missing structures or duplicates the pattern present in the fragment. This kind of pattern regulation is known to be epimorphic, i.e. the new pattern is generated by proliferation in a specialized tissue called the blastema. Pattern regulation is accompanied by the healing of the cut surfaces restoring the continuous epithelia. Wound healing has been considered to be the inductive signal to commence regenerative cell divisions. Although the general outlines of the proliferation dynamics in a regenerating imaginal disc blastema have been well studied, little is known about the mechanisms driving cells into the regenerative cell cycles. In this study, we have investigated the role of Jun N-terminal Kinase (JNK) signaling in the wound healing and regeneration of a Drosophila wing imaginal disc. By utilizing in vivo and in vitro culturing of incised and fragmented discs, we have been able to visualize the dynamics in cellular architecture and gene expression involved in the healing and regeneration process. Our results directly show that homotypic wound healing is not a prerequisite for regenerative cell divisions. We also show that JNK signaling participates in imaginal disc wound healing and is regulated by the physical dynamics of the process, as well as in recruiting cells into the regenerative cell cycles. A model describing the determination of blastema size is discussed.

  6. Targeting Mcl-1 for multiple myeloma (MM) therapy: drug-induced generation of Mcl-1 fragment Mcl-1(128-350) triggers MM cell death via c-Jun upregulation.

    Science.gov (United States)

    Fan, Fengjuan; Tonon, Giovanni; Bashari, Muhammad Hasan; Vallet, Sonia; Antonini, Elena; Goldschmidt, Hartmut; Schulze-Bergkamen, Henning; Opferman, Joseph T; Sattler, Martin; Anderson, Kenneth C; Jäger, Dirk; Podar, Klaus

    2014-02-28

    Myeloid cell leukemia-1 (Mcl-1, HGNC: 6943), a pro-survival member of the Bcl-2 family, plays a crucial role in Multiple Myeloma (MM) pathogenesis and drug resistance, thus representing a promising therapeutic target in MM. A novel strategy to inhibit Mcl-1 activity is the induction of ubiquitin-independent Mcl-1 degradation. Our own and other previous studies have demonstrated caspase-dependent generation of a 28kDa Mcl-1 fragment, Mcl-1(128-350), which inhibits MM cell proliferation and survival. Here, we show that similar to bortezomib, the novel proteasome inhibitors carfilzomib and ixazomib, as well as staurosporine and adaphostin, induce the generation of Mcl-1(128-350) in MM cells. Next, the molecular sequelae downstream of Mcl-1(128-350), which mediate its pro-apoptotic activity, were delineated. Surprisingly, we observed nuclear accumulation of drug-induced or exogenously overexpressed Mcl-1(128-350), followed by elevated mRNA and protein levels of c-Jun, as well as enhanced AP-1 reporter activity. Moreover, drug-induced AP-1 activity was blocked after introducing a point mutation into the highly conserved Mcl-1 caspase-cleavage site Asp127, but not Asp157. Consequently, drug-triggered cell death was significantly decreased in MM cells transfected with Mcl-1 D127A, but not with Mcl-1 D157A. Consistent with these data, treatment with bortezomib triggered c-Jun upregulation followed by apoptosis in Mcl-1(wt/wt), but not Mcl-1(Δ/null) murine embryonic fibroblasts (MEFs). Transfection of a plasmid carrying Mcl-1(wt) into Mcl-1(Δ/null) MEFs restored bortezomib-induced Mcl-1 fragmentation, c-Jun upregulation and AP-1 reporter activity. Finally, our data indicate that drug-induced generation of a pro-apoptotic Mcl-1 fragment followed by c-Jun upregulation may also be a novel therapeutic approach in other tumor entities.

  7. 我国优秀男子花剑运动员朱俊的主要制胜因素分析%Analysis of the Main Factors for the Success of Our Elite Male Foil Fencer Zhu Jun

    Institute of Scientific and Technical Information of China (English)

    张钊雄

    2014-01-01

    Through technical statistics based on six important competitions'video tapes of Zhu Jun,the excellent foil fencer. This thesis find out that attack with beat,distance parry,direct riposte,riposte with a coupe,croise,and counter-attack are six major technique Zhu Jun used in competitions. As technique and efficiency factors are related,this thesis find out speed and distance controlling are main efficiency factors of Zhu Jun. This thesis recommend Zhu Jun to reinforce these factors in later training and competitions. Combine these factors with others,to make them become the ace in the hole.%通过对我国优秀男子花剑运动员朱俊的六场重大赛事录像进行专项技术统计分析,找出了朱俊的主要得分技术为击打进攻、距离防守、直刺还击、交叉还击、击打转移还击和反攻六项。根据技术与制胜因素的对应关系,得出了朱俊的主要制胜因素是快速和距离。认为朱俊在以后的训练和比赛中应该加强快速和距离的特点,并注意运用组合制胜因素,使其成为制胜的“杀手锏”。

  8. MST Kinases Monitor Actin Cytoskeletal Integrity and Signal via c-Jun N-Terminal Kinase Stress-Activated Kinase To Regulate p21Waf1/Cip1 Stability

    OpenAIRE

    Densham, R. M.; E'Neill, Eric; Munro, J; et al, ...

    2009-01-01

    As well as providing a structural framework, the actin cytoskeleton plays integral roles in cell death, survival, and proliferation. The disruption of the actin cytoskeleton results in the activation of the c-Jun N-terminal kinase (JNK) stress-activated protein kinase (SAPK) pathway; however, the sensor of actin integrity that couples to the JNK pathway has not been characterized in mammalian cells. We now report that the mammalian Ste20-like (MST) kinases mediate the activation of the JNK pa...

  9. JNK1/c-Jun and p38 alpha MAPK/ATF-2 pathways are responsible for upregulation of Fas/FasL in human chronic myeloid leukemia K562 cells upon exposure to Taiwan cobra phospholipase A2.

    Science.gov (United States)

    Chen, Ku-Chung; Chiou, Yi-Ling; Chang, Long-Sen

    2009-10-15

    Fas and FasL expression upregulation was found in human leukemia K562 cells upon exposure to Naja naja atra phospholipase A(2) (PLA(2)). PLA(2) treatment induced an increase in intracellular Ca(2+) ([Ca(2+)]i) and ROS generation levels, leading to activation of p38 MAPK and JNK. Suppression of both p38 MAPK and JNK abrogated Fas and FasL upregulation. Unlike PLA(2), catalytically inactive PLA(2) treatment did not markedly increase Fas and FasL protein expression, and p38 MAPK activation was exclusively responsible for catalytically inactive PLA(2)-induced increase in Fas and FasL protein expression. Knockdown of p38 alpha MAPK and JNK1 by siRNA proved that p38 alpha MAPK and JNK1 were involved in ATF-2 and c-Jun phosphorylation, respectively. Compared with the p38 alpha MAPK/ATF-2 pathway, the JNK1/c-Jun pathway played a crucial role in Fas/FasL upregulation. Unlike arachidonic acid, lysophosphatidylcholine mimicked the PLA(2) action in inducing Fas/FasL upregulation. Together with the previous finding that c-Jun and ATF-2 are involved in transcriptional regulation of Fas and FasL, our data suggest that PLA(2) induces Fas and FasL upregulation through p38 alpha MAPK/ATF-2 and JNK1/c-Jun pathways in K562 cells, and PLA(2) catalytic activity is involved in this action. (c) 2009 Wiley-Liss, Inc.

  10. Piceatannol induces Fas and FasL up-regulation in human leukemia U937 cells via Ca2+/p38alpha MAPK-mediated activation of c-Jun and ATF-2 pathways.

    Science.gov (United States)

    Liu, Wen-Hsin; Chang, Long-Sen

    2010-09-01

    To verify whether piceatannol-induced death of leukemia cells was associated with Fas-mediated death pathway, the present study was conducted. Piceatannol-induced apoptotic death of human leukemia U937 cells was characterized by increase in intracellular Ca(2+) concentration ([Ca(2+)]i), ERK inactivation, p38 MPAK activation, degradation of procaspase-8 and production of t-Bid. Piceatannol treatment increased Fas and FasL protein expression, and up-regulated transcription of Fas and FasL mRNA. Down-regulation of FADD blocked piceatannol-induced procaspase-8 degradation and rescued viability of piceatannol-treated cells. Abolition of piceatannol-induced increase in [Ca(2+)]i abrogated p38 MAPK activation and up-regulation of Fas and FasL expression, but restored ERK activation and viability of piceatannol-treated cells. Suppression of p38alpha MAPK or transfection of constitutively active MEK1 abolished piceatannol-induced Fas and FasL up-regulation. Piceatannol treatment repressed ERK-mediated c-Fos phosphorylation but evoked p38alpha MAPK-mediated c-Jun and ATF-2 phosphorylation. Knockdown of c-Fos, c-Jun and ATF-2 by siRNA reflected that c-Fos attenuated the effect of c-Jun and ATF-2 on Fas/FasL up-regulation. Taken together, our data indicate that Fas/FasL up-regulation in piceatannol-treated U937 cells is elicited by Ca(2+)/p38alpha MAPK-mediated activation of c-Jun and ATF-2, and suggest that autocrine Fas-mediated apoptotic mechanism is involved in piceatannol-induced cell death. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

  11. Effects of 2-amino-1-methyl-6-phenylimidazo [4, 5-b] pyridine (PhIP) on histopathology, oxidative stress, and expression of c-fos, c-jun and p16 in rat stomachs.

    Science.gov (United States)

    Li, Ruijin; Tian, Jingjing; Li, Wanqing; Xie, Jingfang

    2013-05-01

    2-Amino-1-methyl-6-phenylimidazo [4, 5-b] pyridine (PhIP) is one of the most abundant heterocyclic amines (HCAs) generated from overcooking meat at high temperatures. To understand the possible mechanism of PhIP-associated stomach cancer, the effects of PhIP on morphology, oxidative stress, gene expression of c-fos, c-jun and p16 in rat stomachs were investigated. The results showed that (1) 15mg/kg body weight PhIP induced obvious histopathological changes in gastric mucosa; (2) PhIP (10 and/or 15mg/kg) significantly decreased superoxide dismutase (SOD) and glutathioneperoxidase (GPx) activities, while increased catalase (CAT) activity compared with the control. With the elevated doses of PhIP, malondialdehyde (MDA) contents, protein carbonyl (PCO) contents and DNA-protein crosslinks (DPC) coefficients were significantly raised in a dose-dependent manner; (3) PhIP at the doses of 10mg/kg and/or 15mg/kg significantly inhibited p16 mRNA and protein expression, whereas enhanced c-fos and c-jun expression relative to control. The data indicated that PhIP could cause stomach injury, oxidative stress in rat stomachs as well as the activation of c-fos and c-jun and inactivation of p16, which may play a role in the pathogenesis of PhIP-associated stomach cancer. Copyright © 2013 Elsevier Ltd. All rights reserved.

  12. On the Application of Audio-lingual Teaching Method Combined with CAI in English Grammar Teaching%听说领先法结合CAI英语语法教学的运用

    Institute of Scientific and Technical Information of China (English)

    杨娜柳

    2015-01-01

    “听说领先法”英语语法教学模式下课堂教学单一枯燥,但通过对同一句型不断地重复练习,学生能慢慢积累掌握相关知识点。教师的主导地位得以充分发挥。在CAI教学模式下,教师可通过声音、图像等调动学生感官,更好地引导学生学习英语语法知识,但是师生缺乏互动,同样效果不佳。主要讨论将这两种教学模式进行有机结合,扬长避短,即通过CAI英语语法教学的实际运用,充分调动学生作为学习主体的能动性,提高英语语法教学效率。%Traditional audio-lingual teaching mode in English grammar teaching is monotonous and tedious but students can grasp the sentence pattern gradually through practicing repeatedly under this teaching pattern and teacher’s leading role is better reinforced. Teacher can lead students to learn English grammar better by means of audio and video with the help of CAI. However the interaction between teacher and students is fewer compared with the traditional teaching mode. The paper mainly discusses the efficient use of combining with these two methods which have their own advantages and drawbacks in order to strengthen students’ learning initiative and improve teaching efficiency.

  13. 一种基于模块化结构的大学英语四级MCAI系统实现方法研究%Implementation of Modularized Multimedia CAI System for CET-4

    Institute of Scientific and Technical Information of China (English)

    余正涛; 宋丽哲; 车文刚; 邵谨; 郭剑毅

    2001-01-01

    Authorware是一种优秀的多媒体开发工具,能实现非常复杂的多媒体接 入及程序流程 控制,但在开发功能结构类似,信息资源丰富的模块时,还存在程序设计复杂,代码重复量 大,模块功能更改困难等问题。本文针对以上问题,在设计大学英语四级多媒体教学系统时 ,提出了一套基于模块化结构的大学英语四级MCAI教学软件的设计思想,并以听力部分为例 ,详细介绍了该部分各功能模块的实现。%Authorware is an excellent tool for developing multime dia systems. It can implement complex multimedia interfacing and program process con trol. However, there still exist problems such as programming complexity, code repetit ion and difficulty of module function updating in re-developing similar modules wit h large quantity of data. This paper purposes a new method of implementing a modul arized Multimedia CAI System for College English Test Band 4 (CET-4). Finally, it illu strates how to implement the functions of modules by a sample for Listening Comprehensio n.

  14. Ketamine inhibits tumor necrosis factor-alpha and interleukin-6 gene expressions in lipopolysaccharide-stimulated macrophages through suppression of toll-like receptor 4-mediated c-Jun N-terminal kinase phosphorylation and activator protein-1 activation.

    Science.gov (United States)

    Wu, Gone-Jhe; Chen, Ta-Liang; Ueng, Yune-Fang; Chen, Ruei-Ming

    2008-04-01

    Our previous study showed that ketamine, an intravenous anesthetic agent, has anti-inflammatory effects. In this study, we further evaluated the effects of ketamine on the regulation of tumor necrosis factor-alpha (TNF-alpha) and interlukin-6 (IL-6) gene expressions and its possible signal-transducing mechanisms in lipopolysaccharide (LPS)-activated macrophages. Exposure of macrophages to 1, 10, and 100 microM ketamine, 100 ng/ml LPS, or a combination of ketamine and LPS for 1, 6, and 24 h was not cytotoxic to macrophages. A concentration of 1000 microM of ketamine alone or in combined treatment with LPS caused significant cell death. Administration of LPS increased cellular TNF-alpha and IL-6 protein levels in concentration- and time-dependent manners. Meanwhile, treatment with ketamine concentration- and time-dependently alleviated the enhanced effects. LPS induced TNF-alpha and IL-6 mRNA syntheses. Administration of ketamine at a therapeutic concentration (100 microM) significantly inhibited LPS-induced TNF-alpha and IL-6 mRNA expressions. Application of toll-like receptor 4 (TLR4) small interfering (si)RNA into macrophages decreased cellular TLR4 levels. Co-treatment of macrophages with ketamine and TLR4 siRNA decreased the LPS-induced TNF-alpha and IL-6 productions more than alone administration of TLR4 siRNA. LPS stimulated phosphorylation of c-Jun N-terminal kinase and translocation of c-Jun and c-Fos from the cytoplasm to nuclei. However, administration of ketamine significantly decreased LPS-induced activation of c-Jun N-terminal kinase and translocation of c-Jun and c-Fos. LPS increased the binding of nuclear extracts to activator protein-1 consensus DNA oligonucleotides. Administration of ketamine significantly ameliorated LPS-induced DNA binding activity of activator protein-1. Therefore, a clinically relevant concentration of ketamine can inhibit TNF-alpha and IL-6 gene expressions in LPS-activated macrophages. The suppressive mechanisms occur through

  15. Effect of c-Jun NH2-terminal kinase-mediated p53 expression on neuron autophagy following traumatic brain injury in rats

    Institute of Scientific and Technical Information of China (English)

    HONG Ming-yan; GAO Jun-ling; CUI Jian-zhong; WANG Kai-jie; TIAN Yan-xia; LI Ran; WANG Hai-tao; WANG Huan

    2012-01-01

    Background Activation of c-Jun NH2-terminal kinase (JNK) has been implicated in neuron apoptosis as well as autophagy in response to various stressors after traumatic brain injury (TBI).However,the underlying molecular pathway remains unclear.Our study assessed whether JNK-mediated p53 phosphorylation might be an important mechanism for enhancing neuron autophagy in response to TBI.Methods A total of 186 male Sprague-Dawley (SD) rats (300-350 g) were used in this study.By randomized block method rats were randomly divided into four groups:sham-operated (n=46),TBI (n=60),TBI + dimethyl sulfoxide (DMSO) (n=40),and TBI + SP600125 (n=40).JNK was treated with SP600125,a specific JNK inhibitor.JNK,p-P53,Beclin-1,damage-regulated autophagy modulator (DRAM) and p-bcl-2 were evaluated by Western blotting analysis.The cellular localization and expression of Beclin-1 and DRAM was observed by immunofluorescence and immunohistochemistry,and the expression of Beclin-1-Bcl-2/Bcl-xL complexes was evaluated by immunoprecipitation.Multiple-group comparisons were conducted using analysis of variance (ANOVA).P values of less than 0.05 were considered statistically significant.Results It was observed that the expression of JNK,p-P53,Beclin-1,DRAM and p-bcl-2 was increasing after TBI,and the expression of Beclin-1 and DRAM was mainly located in the cytoplasm of neurons.But these were significantly inhibited in SP600125 group compared with sham group and TBI+SP600125 group (P <0.05).The expression of Beclin-1-Bcl-2/Bcl-xL complexes was reduced after TBI.Conclusion JNK-mediated p53 phosphorylation might be an important mechanism for enhancing neuron autophagy in response to TBI.

  16. Apigenin attenuates dopamine-induced apoptosis in melanocytes via oxidative stress-related p38, c-Jun NH2-terminal kinase and Akt signaling.

    Science.gov (United States)

    Lin, Mao; Lu, Shan-Shan; Wang, Ao-Xue; Qi, Xiao-Yi; Zhao, Dan; Wang, Zhao-Hui; Man, Mao-Qiang; Tu, Cai-Xia

    2011-07-01

    Accumulating evidence suggests that the occurrence of oxidative stress leads to melanocyte degeneration in vitiligo. Elevated level of dopamine (DA), an initiator of oxidative stress, reportedly is found in patients with vitiligo and induces melanocyte death in vitro. DA-treated melanocytes have been used as a model to search for antioxidants for treating vitiligo. We investigated the protective effects of apigenin against DA-induced apoptosis in melanocytes and the molecular mechanism underlying those effects. Melanocytes with or without pretreatment with apigenin were exposed to DA. Then cell viabilities were measured by MTT assay. Cellular reactive oxygen species (ROS) levels and the percentage of apoptotic cells were detected by flow cytometry analysis. Activation of caspase 3, poly(ADP-ribose) polymerase (PARP) and oxidative stress-related signaling, including p38, c-Jun NH2-terminal kinase (JNK) and Akt, were assessed by Western blotting. Apigenin attenuated DA-induced apoptotic cell death, relieved ROS accumulation and activated caspase 3 and PARP, suggesting the protective effects of apigenin against DA-induced oxidative stress and apoptosis in melanocytes. Moreover, DA induced phosphorylation of p38, JNK and Akt, while inhibitors of p38, JNK and Akt significantly decreased DA-induced apoptosis. However, pretreatment with apigenin significantly inhibited DA-triggered activation of p38, JNK and Akt, suggesting the involvement of p38, JNK and Akt in the protective effects of apigenin against DA-induced cytotoxicity. These results suggest that apigenin attenuates dopamine-induced apoptosis in melanocytes via oxidative stress-related p38, JNK and Akt signaling and therefore could be a potential agent in treating vitiligo. Copyright © 2011 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

  17. Immunohistochemical analysis of the expression of cellular transcription NFκB (p65), AP-1 (c-Fos and c-Jun), and JAK/STAT in leprosy.

    Science.gov (United States)

    Silva, Luciana Mota; Hirai, Kelly Emi; de Sousa, Jorge Rodrigues; de Souza, Juarez; Fuzii, Hellen Thais; Dias, Leonidas Braga; Carneiro, Francisca Regina Oliveira; de Souza Aarão, Tinara Leila; Quaresma, Juarez Antonio Simões

    2015-05-01

    Leprosy is a disease whose clinical spectrum depends on the cytokine patterns produced during the early stages of the immune response. The main objective of this study was to describe the activation pattern of cellular transcription factors and to correlate these factors with the clinical forms of leprosy. Skin samples were obtained from 16 patients with the tuberculoid (TT) form and 14 with the lepromatous (LL) form. The histologic sections were immunostained with anti-c-Fos and anti-c-Jun monoclonal antibodies for investigation of AP-1, anti-NFκB p65 for the study of NFκB, and anti-JAK2, STAT1, STAT3, and STAT4 for investigation of the JAK/STAT pathway. Cells expressing STAT1 were more frequent in the TT form than in LL lesions (P = .0096), in agreement with the protective immunity provided by IFN-γ. STAT4 was also more highly expressed in the TT form than in the LL form (P = .0098). This transcription factor is essential for the development of a Th1 response because it is associated with interleukin-12. NFκB (p65) and STAT4 expression in the TT form showed a strong and significant correlation (r = 0.7556 and P = .0007). A moderate and significant correlation was observed between JAK2 and STAT4 in the TT form (r = 0.6637 and P = .0051), with these factors responding to interleukin-12 in Th1 profiles. The results suggest that STAT1, JAK2, and NFκB, together with STAT4, contribute to the development of cell-mediated immunity, which is able to contain the proliferation of Mycobacterium leprae.

  18. Activation of the KCa3.1 channel contributes to traumatic scratch injury-induced reactive astrogliosis through the JNK/c-Jun signaling pathway.

    Science.gov (United States)

    Yi, Mengni; Dou, Fangfang; Lu, Qin; Yu, Zhihua; Chen, Hongzhuan

    2016-06-15

    Reactive astrogliosis is widely considered to contribute to pathogenic responses to stress and brain injury and to diseases as diverse as ischemia and neurodegeneration. We previously found that expression of the intermediate-conductance calcium-activated potassium channel (KCa3.1) involved in TGF-β-activated astrogliosis. In the present study, we investigated whether migration of cortical astrocytes following mechanical scratch injury involves the KCa3.1 channel, which contributes to Ca(2+)-mediated migration in other cells. We found that scratch injury increased the expression of KCa3.1 protein in reactive astrocytes. Application of the KCa3.1 blocker TRAM-34 decreased glial fibrillary acidic protein (GFAP) expression and slowed migration in a concentration-dependent manner. Application of the Ca(2+) chelators, EGTA and BAPTA-AM, also slowed the migration of astrocytes. Blockade or genetic deletion of KCa3.1 both slowed and dramatically reduced the scratch injuries induced the sharp rise in astrocytes Ca(2+) concentrations. The scratch injury-induced phosphorylation of JNK and c-Jun proteins was also attenuated both by blockade of KCa3.1 with TRAM-34 and in KCa3.1(-/-) astrocytes. Using KCa3.1 knockout mice, we further confirmed that deletion of KCa3.1 reduced expression of GFAP in an in vivo stab wound model. Taken together, our findings highlight a novel role for KCa3.1 in phenotypic modulation of reactive astrocytes and in astrocyte mobilization in response to mechanical stress, providing a potential target for therapeutic intervention in brain injuries.

  19. Testosterone supplementation reverses sarcopenia in aging through regulation of myostatin, c-Jun NH2-terminal kinase, Notch, and Akt signaling pathways.

    Science.gov (United States)

    Kovacheva, Ekaterina L; Hikim, Amiya P Sinha; Shen, Ruoqing; Sinha, Indranil; Sinha-Hikim, Indrani

    2010-02-01

    Aging in rodents and humans is characterized by loss of muscle mass (sarcopenia). Testosterone supplementation increases muscle mass in healthy older men. Here, using a mouse model, we investigated the molecular mechanisms by which testosterone prevents sarcopenia and promotes muscle growth in aging. Aged mice of 22 months of age received a single sc injection of GnRH antagonist every 2 wk to suppress endogenous testosterone production and were implanted subdermally under anesthesia with 0.5 or 1.0 cm testosterone-filled implants for 2 months (n = 15/group). Young and old mice (n = 15/group), of 2 and 22 months of age, respectively, received empty implants and were used as controls. Compared with young animals, a significant (P muscle cell apoptosis coupled with a decrease in gastrocnemius muscles weight (by 16.7%) and muscle fiber cross-sectional area, of both fast and slow fiber types, was noted in old mice. Importantly, such age-related changes were fully reversed by higher dose (1 cm) of testosterone treatment. Testosterone treatment effectively suppressed age-specific increases in oxidative stress, processed myostatin levels, activation of c-Jun NH(2)-terminal kinase, and cyclin-dependent kinase inhibitor p21 in aged muscles. Furthermore, it restored age-related decreases in glucose-6-phosphate dehydrogenase levels, phospho-Akt, and Notch signaling. These alterations were associated with satellite cell proliferation and differentiation. Collectively these results suggest involvement of multiple signal transduction pathways in sarcopenia. Testosterone reverses sarcopenia through stimulation of cellular metabolism and survival pathway together with inhibition of death pathway.

  20. Cytotoxic Activity of 3,6-Dihydroxyflavone in Human Cervical Cancer Cells and Its Therapeutic Effect on c-Jun N-Terminal Kinase Inhibition

    Directory of Open Access Journals (Sweden)

    Eunjung Lee

    2014-08-01

    Full Text Available Previously we have shown that 3,6-dihydroxyflavone (3,6-DHF is a potent agonist of the human peroxisome proliferator-activated receptor (hPPAR with cytotoxic effects on human cervical cancer cells. To date, the mechanisms by which 3,6-DHF exerts its antitumor effects on cervical cells have not been clearly defined. Here, we demonstrated that 3,6-DHF exhibits a novel antitumor activity against HeLa cells with IC50 values of 25 μM and 9.8 μM after 24 h and 48 h, respectively. We also showed that the anticancer effects of 3,6-DHF are mediated via the toll-like receptor (TLR 4/CD14, p38 mitogen-activated protein kinase (MAPK, Jun-N terminal kinase (JNK, extracellular-signaling regulated kinase (ERK, and cyclooxygenase (COX-2 pathways in lipopolysaccharide (LPS-stimulated RAW264.7 cells. We found that 3,6-DHF showed a similar IC50 (113 nM value to that of the JNK inhibitor, SP600125 (IC50 = 118 nM in a JNK1 kinase assay. Binding studies revealed that 3,6-DHF had a strong binding affinity to JNK1 (1.996 × 105 M−1 and that the 6-OH and the carbonyl oxygen of the C ring of 3,6-DHF participated in hydrogen bonding interactions with the carbonyl oxygen and the amide proton of Met111, respectively. Therefore, 3,6-DHF may be a candidate inhibitor of JNKs, with potent anticancer effects.

  1. Junín virus infection of human hematopoietic progenitors impairs in vitro proplatelet formation and platelet release via a bystander effect involving type I IFN signaling.

    Science.gov (United States)

    Pozner, Roberto G; Ure, Agustín E; Jaquenod de Giusti, Carolina; D'Atri, Lina P; Italiano, Joseph E; Torres, Oscar; Romanowski, Victor; Schattner, Mirta; Gómez, Ricardo M

    2010-04-15

    Argentine hemorrhagic fever (AHF) is an endemo-epidemic disease caused by Junín virus (JUNV), a member of the arenaviridae family. Although a recently introduced live attenuated vaccine has proven to be effective, AHF remains a potentially lethal infection. Like in other viral hemorrhagic fevers (VHF), AHF patients present with fever and hemorrhagic complications. Although the causes of the bleeding are poorly understood, impaired hemostasis, endothelial cell dysfunction and low platelet counts have been described. Thrombocytopenia is a common feature in VHF syndromes, and it is a major sign for its diagnosis. However, the underlying pathogenic mechanism has not yet been elucidated. We hypothesized that thrombocytopenia results from a viral-triggered alteration of the megakaryo/thrombopoiesis process. Therefore, we evaluated the impact of JUNV on megakaryopoiesis using an in vitro model of human CD34+ cells stimulated with thrombopoietin. Our results showed that CD34+ cells are infected with JUNV in a restricted fashion. Infection was transferrin receptor 1 (TfR1)-dependent and the surface expression of TfR1 was higher in infected cultures, suggesting a novel arenaviral dissemination strategy in hematopoietic progenitor cells. Although proliferation, survival, and commitment in JUNV-infected cultures were normal, viral infection impaired thrombopoiesis by decreasing in vitro proplatelet formation, platelet release, and P-selectin externalization via a bystander effect. The decrease in platelet release was also TfR1-dependent, mimicked by poly(I:C), and type I interferon (IFN alpha/beta) was implicated as a key paracrine mediator. Among the relevant molecules studied, only the transcription factor NF-E2 showed a moderate decrease in expression in megakaryocytes from either infected cultures or after type I IFN treatment. Moreover, type I IFN-treated megakaryocytes presented ultrastructural abnormalities resembling the reported thrombocytopenic NF-E2(-/-) mouse

  2. Inhibition of spinal astrocytic c-Jun N-terminal kinase (JNK activation correlates with the analgesic effects of ketamine in neuropathic pain

    Directory of Open Access Journals (Sweden)

    Wang Wen

    2011-01-01

    Full Text Available Abstract Background We have previously reported that inhibition of astrocytic activation contributes to the analgesic effects of intrathecal ketamine on spinal nerve ligation (SNL-induced neuropathic pain. However, the underlying mechanisms are still unclear. c-Jun N-terminal kinase (JNK, a member of mitogen-activated protein kinase (MAPK family, has been reported to be critical for spinal astrocytic activation and neuropathic pain development after SNL. Ketamine can decrease lipopolysaccharide (LPS-induced phosphorylated JNK (pJNK expression and could thus exert its anti-inflammatory effect. We hypothesized that inhibition of astrocytic JNK activation might be involved in the suppressive effect of ketamine on SNL-induced spinal astrocytic activation. Methods Immunofluorescence histochemical staining was used to detect SNL-induced spinal pJNK expression and localization. The effects of ketamine on SNL-induced mechanical allodynia were confirmed by behavioral testing. Immunofluorescence histochemistry and Western blot were used to quantify the SNL-induced spinal pJNK expression after ketamine administration. Results The present study showed that SNL induced ipsilateral pJNK up-regulation in astrocytes but not microglia or neurons within the spinal dorsal horn. Intrathecal ketamine relieved SNL-induced mechanical allodynia without interfering with motor performance. Additionally, intrathecal administration of ketamine attenuated SNL-induced spinal astrocytic JNK activation in a dose-dependent manner, but not JNK protein expression. Conclusions The present results suggest that inhibition of JNK activation may be involved in the suppressive effects of ketamine on SNL-induced spinal astrocyte activation. Therefore, inhibition of spinal JNK activation may be involved in the analgesic effects of ketamine on SNL-induced neuropathic pain.

  3. I-mfa domain proteins interact with Axin and affect its regulation of the Wnt and c-Jun N-terminal kinase signaling pathways.

    Science.gov (United States)

    Kusano, Shuichi; Raab-Traub, Nancy

    2002-09-01

    I-mfa has been identified as an inhibitor of myogenic basic helix-loop-helix transcription factors, and a related human I-mfa domain-containing protein (HIC) also has been identified as a protein that regulates Tat- and Tax-mediated expression of viral promoters. HIC and I-mfa represent a family of proteins that share a highly conserved cysteine-rich domain, termed the I-mfa domain. We show here that both I-mfa domain proteins, HIC and I-mfa, interacted in vivo with the Axin complex through their C-terminal I-mfa domains. This interaction inhibited Axin-mediated downregulation of free levels of cytosolic beta-catenin. I-mfa and HIC also both directly interacted with lymphocyte enhancer factor (LEF); however, I-mfa but not HIC significantly inhibited reporter constructs regulated by beta-catenin. The overexpression of HIC but not I-mfa decreased the inhibitory effects of Axin on beta-catenin-regulated reporter constructs, while both HIC and I-mfa decreased Axin-mediated c-Jun N-terminal kinase (JNK) activation. These data reveal for the first time that I-mfa domain proteins interact with the Axin complex and affect Axin regulation of both the Wnt and the JNK activation pathways. Interestingly, HIC differs from I-mfa in that I-mfa affects both Axin function and T-cell factor- or LEF-regulated transcription in the Wnt signaling pathway while HIC affects primarily Axin function.

  4. Protein kinase B/Akt activates c-Jun NH(2)-terminal kinase by increasing NO production in response to shear stress

    Science.gov (United States)

    Go, Y. M.; Boo, Y. C.; Park, H.; Maland, M. C.; Patel, R.; Pritchard, K. A. Jr; Fujio, Y.; Walsh, K.; Darley-Usmar, V.; Jo, H.

    2001-01-01

    Laminar shear stress activates c-Jun NH(2)-terminal kinase (JNK) by the mechanisms involving both nitric oxide (NO) and phosphatidylinositide 3-kinase (PI3K). Because protein kinase B (Akt), a downstream effector of PI3K, has been shown to phosphorylate and activate endothelial NO synthase, we hypothesized that Akt regulates shear-dependent activation of JNK by stimulating NO production. Here, we examined the role of Akt in shear-dependent NO production and JNK activation by expressing a dominant negative Akt mutant (Akt(AA)) and a constitutively active mutant (Akt(Myr)) in bovine aortic endothelial cells (BAEC). As expected, pretreatment of BAEC with the PI3K inhibitor (wortmannin) prevented shear-dependent stimulation of Akt and NO production. Transient expression of Akt(AA) in BAEC by using a recombinant adenoviral construct inhibited the shear-dependent stimulation of NO production and JNK activation. However, transient expression of Akt(Myr) by using a recombinant adenoviral construct did not induce JNK activation. This is consistent with our previous finding that NO is required, but not sufficient on its own, to activate JNK in response to shear stress. These results and our previous findings strongly suggest that shear stress triggers activation of PI3K, Akt, and endothelial NO synthase, leading to production of NO, which (along with O(2-), which is also produced by shear) activates Ras-JNK pathway. The regulation of Akt, NO, and JNK by shear stress is likely to play a critical role in its antiatherogenic effects.

  5. Intrathecal administration of low-dose nociceptin/orphanin FQ induces allodynia via c-Jun N-terminal kinase and monocyte chemoattractant protein-1.

    Science.gov (United States)

    Kawabata, Kenta; Nishimura, Isamu; Fujiwara, Takeshi; Terauchi, Shoko; Minami, Toshiaki; Ito, Seiji; Okuda-Ashitaka, Emiko

    2016-06-01

    Pathological chronic pain, which is frequently associated with prolonged tissue damage, inflammation, tumour invasion, and neurodegenerative diseases, gives rise to hyperalgesia and allodynia. We previously reported that intrathecal administration of nociceptin/orphanin FQ (N/OFQ), an endogenous ligand for the orphan opioid receptor-like receptor, in the femtomole range induces touch-evoked allodynia. N/OFQ has been implicated in multiple signalling pathways, such as inhibition of cAMP production and Ca(2+) channels, or activation of K(+) channels and mitogen-activated protein kinase, although the signalling pathways of N/OFQ-induced allodynia remain unclear. To address these issues, we developed an ex vivo mitogen-activated protein kinase assay by using intact slices of mouse spinal cord. N/OFQ markedly increased the phosphorylation of c-Jun N-terminal kinase (JNK) in the superficial dorsal horn of the spinal cord. The N/OFQ-stimulated JNK phosphorylation was significantly inhibited by pertussis toxin, the phospholipase C inhibitor U73122, and the inositol trisphosphate receptor antagonist Xestospongin C. Intrathecal administration of the JNK inhibitor SP600125 inhibited N/OFQ-evoked allodynia. The N/OFQ-induced increase in JNK phosphorylation was observed in astrocytes that expressed glial fibrillary acidic protein. N/OFQ also induced monocyte chemoattractant protein-1 (MCP-1) release via the JNK pathway, and N/OFQ-induced JNK phosphorylation was observed in MCP-1-immunoreactive astrocytes. Intrathecal administration of the MCP-1 receptor antagonist RS504393 inhibited N/OFQ-evoked allodynia. These results suggest that, in the spinal dorsal horn, N/OFQ induces allodynia through activation of JNK via the phospholipase C-inositol trisphosphate pathway, which is coupled to pertussis toxin-sensitive G-protein, and following the release of MCP-1 from astrocytes.

  6. (-)-Epigallocatechin-3-gallate decreases thrombin/paclitaxel-induced endothelial tissue factor expression via the inhibition of c-Jun terminal NH2 kinase phosphorylation

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Huang-Joe [Institute of Biotechnology, National Tsing Hua University, No. 101, Section 2, Kuang Fu Road, Hsinchu 30013, Taiwan (China); Division of Cardiology, Department of Medicine, China Medical University Hospital, No. 2, Yuh-Der Road, Taichung 40447, Taiwan (China); Lo, Wan-Yu [Department of Medical Research, China Medical University Hospital, No. 2, Yuh-Der Road, Taichung 40447, Taiwan (China); Graduate Integration of Chinese and Western Medicine, China Medical University, No. 91, Hsueh-Shih Road, Taichung 40402, Taiwan (China); Lu, Te-Ling [School of Pharmacy, China Medical University, No. 91, Hsueh-Shih Road, Taichung 40402, Taiwan (China); Huang, Haimei, E-mail: hmhuang@life.nthu.edu.tw [Institute of Biotechnology, National Tsing Hua University, No. 101, Section 2, Kuang Fu Road, Hsinchu 30013, Taiwan (China)

    2010-01-01

    Patients with paclitaxel-eluting stents are concerned with stent thrombosis caused by premature discontinuation of dual antiplatelet therapy or clopidogrel resistance. This study investigates the effect of (-)-epigallocatechin-3-gallate (EGCG) on the expression of thrombin/paclitaxel-induced endothelial tissue factor (TF) expressions in human aortic endothelial cells (HAECs). EGCG was nontoxic to HAECs at 6 h up to a concentration of 25 {mu}mol/L. At a concentration of 25 {mu}mol/L, EGCG pretreatment potently inhibited both thrombin-stimulated and thrombin/paclitaxel-stimulated endothelial TF protein expression. Thrombin and thrombin/paclitaxel-induced 2.6-fold and 2.9-fold increases in TF activity compared with the control. EGCG pretreatment caused a 29% and 38% decrease in TF activity on thrombin and thrombin/paclitaxel treatment, respectively. Real-time polymerase chain reaction (PCR) showed that thrombin and thrombin/paclitaxel-induced 3.0-fold and 4.6-fold TF mRNA expressions compared with the control. EGCG pretreatment caused an 82% and 72% decrease in TF mRNA expression on thrombin and thrombin/paclitaxel treatment, respectively. The c-Jun terminal NH2 kinase (JNK) inhibitor SP600125 reduced thrombin/paclitaxel-induced TF expression. Furthermore, EGCG significantly inhibited the phosphorylation of JNK to 49% of thrombin/paclitaxel-stimulated HAECs at 60 min. Immunofluorescence assay did not show an inhibitory effect of EGCG on P65 NF-{kappa}B nuclear translocation in the thrombin/paclitaxel-stimulated endothelial cells. In conclusion, EGCG can inhibit TF expression in thrombin/paclitaxel-stimulated endothelial cells via the inhibition of JNK phosphorylation. The unique property of EGCG may be used to develop a new drug-eluting stent by co-coating EGCG and paclitaxel.

  7. Antcin H Protects Against Acute Liver Injury Through Disruption of the Interaction of c-Jun-N-Terminal Kinase with Mitochondria.

    Science.gov (United States)

    Huo, Yazhen; Win, Sanda; Than, Tin Aung; Yin, Shutao; Ye, Min; Hu, Hongbo; Kaplowitz, Neil

    2017-02-10

    Antrodia Camphorate (AC) is a mushroom that is widely used in Asian countries to prevent and treat various diseases, including liver diseases. However, the active ingredients that contribute to the biological functions remain elusive. The purpose of the present study is to test the hepatoprotective effect of Antcin H, a major triterpenoid chemical isolated from AC, in murine models of acute liver injury. We found that Antcin H pretreatment protected against liver injury in both acetaminophen (APAP) and galactosamine/tumor necrosis factor (TNF)α models. More importantly, Antcin H also offered a significant protection against acetaminophen-induced liver injury when it was given 1 h after acetaminophen. The protection was verified in primary mouse hepatocytes. Antcin H prevented sustained c-Jun-N-terminal kinase (JNK) activation in both models. We excluded an effect of Antcin H on acetaminophen metabolism and TNF receptor signaling and excluded a direct effect as a free radical scavenger or JNK inhibitor. Since the sustained JNK activation through its interaction with mitochondrial Sab, leading to increased mitochondrial reactive oxygen species (ROS), is pivotal in both models, we examined the effect of Antcin H on p-JNK binding to mitochondria and impairment of mitochondrial respiration. Antcin H inhibited the direct effect of p-JNK on isolated mitochondrial function and binding to isolated mitochondria. Innovation and Conclusion: Our study has identified Antcin H as a novel active ingredient that contributes to the hepatoprotective effect of AC, and Antcin H protects against liver injury through disruption of the binding of p-JNK to Sab, which interferes with the ROS-dependent self-sustaining activation of MAPK cascade. Antioxid. Redox Signal. 26, 207-220.

  8. Pharmacokinetic and tissue distribution studies of 1,9-pyrazoloanthrone, a c-Jun-N-terminal kinase inhibitor in Wistar rats by a simple and sensitive HPLC method.

    Science.gov (United States)

    Ambhore, Nilesh Sudhakar; Yamjala, Karthik; Mohire, Shubhashri; Raju, Kalidhindi Rama Satyanarayana; Mulukutla, Shashank; Murthy, Vishakantha; Tondhawada, Mahesh; Elango, Kannan

    2016-02-20

    JNK pathway activates c-Jun(s) which are responsible for cell apoptosis; as a result, inhibitors of JNK pathway have the potential to prevent dopaminergic neurons from death and decrease the loss of dopamine in substantia nigra pars compacta (SNpc). Recent in-vitro studies show that 1,9-pyrazoloanthrone (1,9-P) a potent JNK-3 inhibitor prevents the apoptosis of dopaminergic cells of brain. In the present study we formulated liposomes to increase the bioavailability of 1,9-P in the brain and developed a simple, sensitive and selective high performance liquid chromatographic method and validated for the estimation of 1,9-P in Wistar rat plasma and tissue samples. Plasma and tissue samples were extracted by protein precipitation technique using acetonitrile (ACN) and rasagiline as the internal standards. Chromatography was performed on Hibar C18 column with mobile phase of ammonium acetate (10mM, pH 8.0 adjusted with ammonia) and ACN at a flow rate of 1mL/min. The lower limit of quantification of the developed method was found to be 2.0ng/mL and 4.0ng/g in plasma and tissue samples respectively. The liposomes of 1,9-P administered to animals at the dose equivalent to 15mg/kg orally demonstrated remarkable absorption into the systemic circulation with maximum concentration (∼7500ng/mL) within 2.0h. The order of the area under curve was found to be kidney>liver>brain>lungs>spleen>heart. The liposomes of 1,9-P were rapidly taken up into brain and showed a good brain concentration after 2.0h; sustenance up to 4.0h was achieved which is better than 1,9-P solution.

  9. Jun kinase-induced overexpression of leukemia-associated Rho GEF (LARG) mediates sustained hypercontraction of longitudinal smooth muscle in inflammation.

    Science.gov (United States)

    Al-Shboul, Othman; Nalli, Ancy D; Kumar, Divya P; Zhou, Ruizhe; Mahavadi, Sunila; Kuemmerle, John F; Grider, John R; Murthy, Karnam S

    2014-06-15

    The signaling pathways mediating sustained contraction of mouse colonic longitudinal smooth muscle and the mechanisms involved in hypercontractility of this muscle layer in response to cytokines and TNBS-induced colitis have not been fully explored. In control longitudinal smooth muscle cells, ACh acting via m3 receptors activated sequentially Gα12, RhoGEF (LARG), and the RhoA/Rho kinase pathway. There was abundant expression of MYPT1, minimal expression of CPI-17, and a notable absence of a PKC/CPI-17 pathway. LARG expression was increased in longitudinal muscle cells isolated from muscle strips cultured for 24 h with IL-1β or TNF-α or obtained from the colon of TNBS-treated mice. The increase in LARG expression was accompanied by a significant increase in ACh-stimulated Rho kinase and ZIP kinase activities, and sustained muscle contraction. The increase in LARG expression, Rho kinase and ZIP kinase activities, and sustained muscle contraction was abolished in cells pretreated with the Jun kinase inhibitor, SP600125. Expression of the MLCP activator, telokin, and MLCP activity were also decreased in longitudinal muscle cells from TNBS-treated mice or from strips treated with IL-1β or TNF-α. In contrast, previous studies had shown that sustained contraction in circular smooth muscle is mediated by sequential activation of Gα13, p115RhoGEF, and dual RhoA-dependent pathways involving phosphorylation of MYPT1 and CPI-17. In colonic circular smooth muscle cells isolated from TNBS-treated mice or from strips treated with IL-1β or TNF-α, CPI-17 expression and sustained muscle contraction were decreased. The disparate changes in the two muscle layers contribute to intestinal dysmotility during inflammation.

  10. Arecoline-induced pro-fibrotic proteins in LLC-PK1 cells are dependent on c-Jun N-terminal kinase.

    Science.gov (United States)

    Lin, Sheng-Hsuan; Chiou, Shean-Jaw; Ho, Wan-Ting; Chuang, Chao-Tang; Chuang, Lea-Yea; Guh, Jinn-Yuh

    2016-02-17

    Areca nut (AN) chewing is associated with chronic kidney disease (CKD). However, the molecular mechanisms of AN-induced CKD are not known. Thus, we studied the effects of arecoline, a major alkaloid of AN, on proximal tubule (LLC-PK1) cells in terms of cytotoxicity, fibrosis, transforming growth factor-β (TGF-β) and c-Jun N-terminal kinase (JNK). We found that arecoline dose (0.1-0.5mM) and time (24-72h)-dependently induced cytotoxicity without causing cell death. Arecoline (0.25 mM) also time-dependently (24-72h) increased fibronectin and plasminogen activator inhibitor-1 (PAI1) protein expressions. Arecoline (0.25 mM) time-dependently (24-72h) increased TGF-β gene transcriptional activity and supernatant levels of active TGF-β1. Moreover, arecoline (0.25 mM) activated JNK while SP600125 (a JNK inhibitor) attenuated arecoline-induced TGF-β gene transcriptional activity. SP600125, but not SB431542 (a TGF-β receptor type I kinase inhibitor), attenuated arecoline-induced fibronectin and PAI1 protein expressions. Finally, tubulointerstitial fibrosis occurred and renal cortical expressions of fibronectin and PAI1 proteins increased in arecoline-fed mice at 24 weeks. We concluded that arecoline induced tubulointerstitial fibrosis in mice while arecoline-induced TGF-β and pro-fibrotic proteins (fibronectin, PAI1) are dependent on JNK in LLC-PK1 cells. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  11. Activation of Tax protein by c-Jun-N-terminal kinase is not dependent on the presence or absence of the early growth response-1 gene product.

    Science.gov (United States)

    Parra, Eduardo; Gutierréz, Luís; Ferreira, Jorge

    2016-02-01

    The Tax protein of human T cell leukemia virus type 1 plays a major role in the pathogenesis of adult T cell leukemia (ATL), an aggressive neoplasia of CD4+ T cells. In the present study, we investigated whether the EGR-1 pathway is involved in the regulation of Tax-induced JNK expression in human Jurkat T cells transfected to express the Tax protein in the presence or absence of PMA or ionomycin. Overexpression of EGR-1 in Jurkat cells transfected to express Tax, promoted the activation of several genes, with the most potent being those that contained AP-1 (Jun/c-Fos), whereas knockdown of endogenous EGR-1 by small interfering RNA (siRNA) somewhat reduced Tax-mediated JNK-1 transcription. Additionally, luciferase-based AP-1 and NF-κB reporter gene assays demonstrated that inhibition of EGR-1 expression by an siRNA did not affect the transcriptional activity of a consensus sequence of either AP-1 or NF-κB. On the other hand, the apoptosis assay, using all-trans retinoic acid (ATRA) as an inducer of apoptosis, confirmed that siRNA against EGR-1 failed to suppress ATRA-induced apoptosis in Jurkat and Jurkat-Tax cells, as noted by the low levels of both DEVDase activity and DNA fragmentation, indicating that the induction of apoptosis by ATRA was Egr-1-independent. Finally, our data showed that activation of Tax by JNK-1 was not dependent on the EGR-1 cascade of events, suggesting that EGR-1 is important but not a determinant for the activity for Tax-induced proliferation of Jurkat cells.

  12. Hydrogen-Rich Saline Attenuates Lipopolysaccharide-Induced Heart Dysfunction by Restoring Fatty Acid Oxidation in Rats by Mitigating C-Jun N-Terminal Kinase Activation.

    Science.gov (United States)

    Tao, Bingdong; Liu, Lidan; Wang, Ni; Tong, Dongyi; Wang, Wei; Zhang, Jin

    2015-12-01

    Sepsis is common in intensive care units (ICU) and is associated with high mortality. Cardiac dysfunction complicating sepsis is one of the most important causes of this mortality. This dysfunction is due to myocardial inflammation and reduced production of energy by the heart. A number of studies have shown that hydrogen-rich saline (HRS) has a beneficial effect on sepsis. Therefore, we tested whether HRS prevents cardiac dysfunction by increasing cardiac energy. Four groups of rats received intraperitoneal injections of one of the following solutions: normal saline (NS), HRS, lipopolysaccharide (LPS), and LPS plus HRS. Cardiac function was measured by echocardiography 8 h after the injections. Gene and protein expression related to fatty acid oxidation (FAO) were measured by quantitative polymerase chain reaction (PCR) and Western blot analysis. The injection of LPS compromised heart function through decreased fractional shortening (FS) and increased left ventricular diameter (LVD). The addition of HRS increased FS, palmitate triphosphate, and the ratio of phosphocreatinine (PCr) to adenosine triphosphate (ATP) as well as decreasing LVD. The LPS challenge reduced the expression of genes related to FAO, including perioxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), perioxisome proliferator-activated receptor alpha (PPARα), Estrogen-related receptor alpha (ERRα), and their downstream targets, in mRNA and protein level, which were attenuated by HRS. However, HRS had little effect on glucose metabolism. Furthermore, HRS inhibited c-Jun N-terminal kinase (JNK) activation in the rat heart. Inhibition of JNK by HRS showed beneficial effects on LPS-challenged rats, at least in part, by restoring cardiac FAO.

  13. Low Dose Acetaminophen Induces Reversible Mitochondrial Dysfunction Associated with Transient c-Jun N-Terminal Kinase Activation in Mouse Liver.

    Science.gov (United States)

    Hu, Jiangting; Ramshesh, Venkat K; McGill, Mitchell R; Jaeschke, Hartmut; Lemasters, John J

    2016-03-01

    Acetaminophen (APAP) overdose causes hepatotoxicity involving mitochondrial dysfunction and c-jun N-terminal kinase (JNK) activation. Because the safe limit of APAP dosing is controversial, our aim was to evaluate the role of the mitochondrial permeability transition (MPT) and JNK in mitochondrial dysfunction after APAP dosing considered nontoxic by criteria of serum alanine aminotransferase (ALT) release and histological necrosis in vivo. C57BL/6 mice were given APAP with and without the MPT inhibitor, N-methyl-4-isoleucine cyclosporin (NIM811), or the JNK inhibitor, SP600125. Fat droplet formation, cell viability, and mitochondrial function in vivo were monitored by intravital multiphoton microscopy. Serum ALT, liver histology, total JNK, and activated phospho(p)JNK were also assessed. High APAP (300 mg/kg) caused ALT release, necrosis, irreversible mitochondrial dysfunction, and hepatocellular death. By contrast, lower APAP (150 mg/kg) caused reversible mitochondrial dysfunction and fat droplet formation in hepatocytes without ALT release or necrosis. Mitochondrial protein N-acetyl-p-benzoquinone imine adducts correlated with early JNK activation, but irreversible mitochondrial depolarization and necrosis at high dose were associated with sustained JNK activation and translocation to mitochondria. NIM811 prevented cell death and/or mitochondrial depolarization after both high and low dose APAP. After low dose, SP600125 decreased mitochondrial depolarization. In conclusion, low dose APAP produces reversible MPT-dependent mitochondrial dysfunction and steatosis in hepatocytes without causing ALT release or necrosis, whereas high dose leads to irreversible mitochondrial dysfunction and cell death associated with sustained JNK activation. Thus, nontoxic APAP has the potential to cause transient mitochondrial dysfunction that may synergize with other stresses to promote liver damage and steatosis.

  14. 人胎冠状动脉原位杂交c-myc和jun原癌基因表达%Expression of proto - oncogenes c - myc and jun in human coronary artery ruring development

    Institute of Scientific and Technical Information of China (English)

    蔡维君; 陈新平; 伍校琼; 罗学港

    2004-01-01

    目的研究原癌基因c-myc和jun在人胎冠状动脉发育过程中的表达与平滑肌细胞增殖的关系.方法用原位杂交方法检测,胎龄分别为16周、22周(因治疗需要引产)的胎儿和意外死亡的足月胎儿冠状动脉前降支c-myc mRNA和jun mRNA的表达水平.杂交反应产物用图像分析仪(MIAS300)作定量分析.结果C-myc mRNA原位杂交反应产物与被测血管区域面积的百分比在16周、22周和足月胎儿分别是70、56和10;Jun mRNA的杂交信反应产物与被测血管区域面积的百分比在这三个时期分别是68、53和8.两个原癌基因在不同阶段的表达均具有显著性差异.结论本实验首次报道c-myc和jun在人胎冠状动脉发育过程中平滑肌的表达图型,c-myc和jun在胎儿冠状动脉平滑肌细胞增殖和内膜的形成过程中可能具有重要的调控作用.%Objective: To investigate the expression of protooncogenes, c - myc and jun, in human coronary artery during development. Methods: In situ hybridization was employed to detect c - myc mRNA and jun mRNA in human coronary artery from aborted fetus with embryonic ages from week 16 to 22 due to treatment requirements. In addition, 3 cases of full term human fetus died of accident were also studied. Hybridized signals were quantified with a computer - assisted image - analyzing system ( MIAS 300 ). Results: The ratio of hybridized signal of c - myc to the area of vascular wall detected were 0.7, 0.54 and 0.10 respectively corresponding to the embryonic ages, 16 weeks,22 weeks and full term. Similar results with the ratio of 0.68, 0.53 and 0.08 for jun mRNA at above embryonic ages was also found. The levels of c - myc and jun mRNA expressed at different embryonic stage showed a significant difference. Conclusions: We first reported the expression of proto - oncogenes, c - myc and jun, in human coronary artery during embryonic development. These two proto - oncogenes may play an important role in the

  15. Cai Hua, L’homme pensé par l’homme, Du statut scientifique des sciences sociales (Man thought by Man. About the scientific status of social sciences), Paris, PUF, 2008, 214 pp. et Laurent Barry, La parenté (Kinship), Paris, Gallimard, 2008, 567 pp.

    OpenAIRE

    2012-01-01

    Two recent works reintroduce China into the anthropology of kinship. Cai Hua and Laurent Barry are both students of Françoise Héritier, who at the Collège de France has revitalised our understanding of the systems of African kinship. Their two books, similarly constructed, devote considerable space to the systems of the Han. The anthropology of kinship, a discipline founded in 1870 by Lewis Henry Morgan’s Systems of Consanguinity and Affinity of the Human Family, and revived in 1949 by the th...

  16. Epania gressitti Huang, Chen & Cai, a new species intercepted in imported ebony timber from Papua New Guinea at Hainan port%海南口岸从巴新进境柿属木材中截获天牛新种——嘉氏萎鞘天牛

    Institute of Scientific and Technical Information of China (English)

    蔡波; 敖苏; 韩玉春; 徐卫; 刘福秀; 林明光; 李伟东; 韩晓晖; 李治道

    2015-01-01

    海南口岸从巴布亚新几内亚进境柿属(Diospyros sp.)木材中截获一种天牛,经鉴定为天牛新种——嘉氏萎鞘天牛(Epania gressitti Huang,Chen&Cai,2014).本文对该种的形态特征进行了重描述,增加雄性生殖器的形态描述,并编制近似种检索表,供检疫鉴定时参考.

  17. Mitogen-activated protein kinases (p38 and c-Jun NH2-terminal kinase) are differentially regulated during cardiac volume and pressure overload hypertrophy.

    Science.gov (United States)

    Sopontammarak, Somkiat; Aliharoob, Assad; Ocampo, Catherina; Arcilla, Rene A; Gupta, Mahesh P; Gupta, Madhu

    2005-01-01

    Chronic pressure overload (PO) and volume overload (VO) result in morphologically and functionally distinct forms of myocardial hypertrophy. However, the molecular mechanism initiating these two types of hypertrophy is not yet understood. Data obtained from different cell types have indicated that the mitogen-activated protein kinases (MAPKs) comprising c-Jun NH2-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and p38 play an important role in transmitting signals of stress stimuli to elicit the cellular response. We tested the hypothesis that early induction of MAPKs differs in two types of overload on the heart and associates with distinct expression of hypertrophic marker genes, namely ANF, alpha-myosin heavy chain (alpha-MHC), and beta-MHC. In rats, VO was induced by aortocaval shunt and PO by constriction of the abdominal aorta. The PO animals were further divided into two groups depending on the severity of the constriction, mild (MPO) and severe pressure overload (SPO), having 35 and 85% aortic constriction, respectively. Early changes in MAPK activity (2-120 min and 1 to 2 d) were analyzed by the in vitro kinase assay using kinase-specific antibodies for p38, JNK, and ERK2. The change in expression of hypertrophy marker genes was examined by Northern blot analysis. In VO hypertrophy, the activity of p38 was markedly increased (10-fold), without changing the activity of ERK and JNK. However, during PO hypertrophy, the activity of JNK was significantly increased (two- to sixfold) and depended on the severity of the load. The activity of p38 was not changed in MPO hypertrophy, whereas it was slightly elevated (50%) in hearts with SPO. Similarly, ERK activity was not changed in hearts with MPO, but a transient rise in activity was observed in hearts with SPO. The expression of ANF and beta-MHC genes was elevated in both PO and VO hypertrophy; however, this change was much greater in hearts subjected to PO than VO hypertrophy. Alpha

  18. Asháninka medicinal plants: a case study from the native community of Bajo Quimiriki, Junín, Peru

    Directory of Open Access Journals (Sweden)

    Luziatelli Gaia

    2010-08-01

    Full Text Available Abstract Background The Asháninka Native Community Bajo Quimiriki, District Pichanaki, Junín, Peru, is located only 4 km from a larger urban area and is dissected by a major road. Therefore the loss of traditional knowledge is a main concern of the local headman and inhabitants. The present study assesses the state of traditional medicinal plant knowledge in the community and compares the local pharmacopoeia with the one from a related ethnic group. Methods Fieldwork was conducted between July and September 2007. Data were collected through semi-structured interviews, collection of medicinal plants in the homegardens, forest walks, a walk along the river banks, participant observation, informal conversation, cross check through voucher specimens and a focus group interview with children. Results Four-hundred and two medicinal plants, mainly herbs, were indicated by the informants. The most important families in terms of taxa were Asteraceae, Araceae, Rubiaceae, Euphorbiaceae, Solanaceae and Piperaceae. Eighty-four percent of the medicinal plants were wild and 63% were collected from the forest. Exotics accounted to only 2% of the medicinal plants. Problems related to the dermal system, digestive system, and cultural belief system represented 57% of all the medicinal applications. Some traditional healers received non-indigenous customers, using their knowledge as a source of income. Age and gender were significantly correlated to medicinal plant knowledge. Children knew the medicinal plants almost exclusively by their Spanish names. Sixteen percent of the medicinal plants found in this community were also reported among the Yanesha of the Pasco Region. Conclusions Despite the vicinity to a city, knowledge on medicinal plants and cultural beliefs are still abundant in this Asháninka Native Community and the medicinal plants are still available in the surroundings. Nevertheless, the use of Spanish names for the medicinal plants and the shift of

  19. Percepción de las acciones de responsabilidad social en empresas de la región Junín

    Directory of Open Access Journals (Sweden)

    Jaime Castilla Barraza

    2014-06-01

    Full Text Available Objetivos: Mostrar la percepción de los pobladores sobre la implementación de acciones de responsabilidad social de las empresas que operan en las ciudades de La Oroya, Concepción y Huancayo de la región Junín; establecer las expectativas y demandas de la población y analizar los factores relacionados con conflictos sociales que se reclama al empresariado. Métodos: La investigación fue de tipo básico, nivel descriptivo y diseño transversal. Se recurrió a la revisión de literatura especializada, con un trabajo de campo de carácter mixto, a través de la aplicación de cuestionarios, entrevistas y grupos focales con pobladores, decisores y especialistas. Resultados: Las comunidades manifestaron que las empresas nunca han mostrado interés de apoyo, considerando que su labor en responsabilidad social es insuficiente (63,3%, toda vez que solo producen con fines lucrativos; debieron respaldar sus pedidos en educación (68,4% opinó que la inversión fue insuficiente; salud (68,9% lo consideró insuficiente; y contratación de la mano de obra de los pobladores de la zona (62,6% señaló que fue insuficiente. Conclusiones: Dados los niveles de insatisfacción en educación y empleabilidad, principalmente, la disconformidad en estas poblaciones termina transformándose en conflictos sociales, por lo que las instituciones públicas y privadas tienen el imperativo ético y estratégico de generar modelos que respondan a la diversidad cultural y desigualdad. En la búsqueda de un modelo de responsabilidad social, generado a partir de las demandas y expectativas de la población de las zonas donde operan diferentes empresas, debe tenerse en cuenta el cómo generar altos niveles de satisfacción en la población con la que interactúan.

  20. Protocatechuic aldehyde inhibits TNF-α-induced fibronectin expression in human umbilical vein endothelial cells via a c-Jun N-terminal kinase dependent pathway.

    Science.gov (United States)

    Tong, Yue-Feng; Liu, Yong; Hu, Zhi-Xing; Li, Zhe-Cheng; A, Agula

    2016-01-01

    Fibronectin (FN) is one of the most important extracellular matrix proteins and plays an important role in the pathogenesis of atherosclerosis (AS). The aim of the present study was to evaluate the effect of a potent, water-soluble antioxidant, protocatechuic aldehyde (PA), which is derived from the Chinese herb Salvia miltiorrhiza, on the expression of FN in human umbilical vein endothelial cells (HUVECs) stimulated with tumor necrosis factor-α (TNF-α). The pharmacological effects of PA on the production of FN were investigated using ELISA and western blot analysis. In addition, ELISA and western blot analysis were used to examine the activation and suppression of the mitogen-activated protein kinase (MAPK) pathways and nuclear factor (NF)-κB in TNF-α-stimulated HUVECs, in order to explore the underlying pharmacological mechanism of PA. The inhibitory effect of PA on the total generation of reactive oxygen species (ROS) in TNF-α-stimulated HUVECs was assessed using 2',7'-dichlorofluorescein diacetate. Pretreatment of HUVECs with PA (0.15, 0.45 and 1.35 mM) for 18 h markedly attenuated the TNF-α-stimulated FN surface expression and secretion in a dose-dependent manner. Intracellular ROS generation and the expression of extracellular signal-regulated kinase 1 and 2 (ERK1/2), c-Jun N-terminal kinase (JNK) and p38 MAPK (p38) were significantly induced by TNF-α (2 ng/ml) in HUVECs. TNF-α-induced ROS generation and JNK activation were inhibited by PA in a concentration-dependent manner. By contrast, ERK1/2 and p38 activation was not significantly affected by PA. Pretreatment of HUVECs with PA for 18 h markedly attenuated TNF-α-stimulated NF-κB activation. In conclusion, the present findings suggest that PA inhibits TNF-α-induced FN expression in HUVECs through a mechanism that involves ROS/JNK and NF-κB.

  1. [Effect of Acupuncture Intervention on c-jun N-terminal Kinase Signaling in the Hippocampus in Rats with Forced Swimming Stress].

    Science.gov (United States)

    Guo, Yu; Xu, Ke; Bao, Wu-ye; Wang, Yu; Zhang, Xu-hui; Xu, Ming-min; Yu, Miao; Zhang, Chun-tao; Zhao, Bing-cong; Wu, Ji-hong; Tu, Ya

    2016-02-01

    To observe the effect of acupuncture on c-jun N-terminal Kinase (JNK) signaling in the hippocampus in rats with forced-swimming stress, so as to reveal its underlying mechanism in relieving depression-like motor response. Forty-eight Sprague-Dawley rats were randomly divided into 8 groups as control, control + JNK inhibitor (SP 600125) , model, model + SP 600125, acupuncture, acupuncture + SP 600125, Fluoxetine (an anti-depressant) , and Fluoxetine + SP 600125 (n = 6 in each group). The depression-like behavior (immobility) model was established by forcing the rat to swim in a glass-cylinder and solitary raise. Acupuncture stimulation was applied to "Baihui" (GV-20) and "Yintang" (GV 29) for 20 min before forced swimming and once again 24 h later.. The rats of the Fluoxetine and Fluoxetine+ SP 600125 groups were treated by intragastric administration of fluoxetine 10 mL (1.8 mg)/kg before forced swimming and once again 24 h thereafter. The rats of the model + SP 600125 and acupuncture + SP 600125 groups were treated by intraperitoneal injection of SP 600125 (10 mg/kg) 90 min before forced swimming and 30 min before acupuncture intervention, respectively. The immobility duration of rats in the water glass-cylinder was used to assess their depression-like behavior response. The expression levels of protein kinase kinase 4 (MKK 4), MKK 7, JNK, and phosphorylated JNK (p-JNK) in the hippocampus were detected by Western blot. Compared to the control group, the duration of immobility, and the expression levels of hippocampal MKK 4, MKK 7, and p-JNK proteins were significantly increased in the model group (P acupuncture, acupuncture + SP 600125, Fluoxetine and Fluoxetine + SP 600125 groups, the expression levels of hippocampal MKK 4 and MKK 7 proteins in the Fluoxetine + SP 600125 group, and those of p-JNK protein in the acupuncture, acupuncture + SP 600125, model + SP 600125, Fluoxetine and Fluoxetine + SP 600125 groups were considerably decreased (P acupuncture

  2. Lower susceptibility of female mice to acetaminophen hepatotoxicity: Role of mitochondrial glutathione, oxidant stress and c-jun N-terminal kinase

    Energy Technology Data Exchange (ETDEWEB)

    Du, Kuo; Williams, C. David; McGill, Mitchell R.; Jaeschke, Hartmut, E-mail: hjaeschke@kumc.edu

    2014-11-15

    Acetaminophen (APAP) overdose causes severe hepatotoxicity in animals and humans. However, the mechanisms underlying the gender differences in susceptibility to APAP overdose in mice have not been clarified. In our study, APAP (300 mg/kg) caused severe liver injury in male mice but 69–77% lower injury in females. No gender difference in metabolic activation of APAP was found. Hepatic glutathione (GSH) was rapidly depleted in both genders, while GSH recovery in female mice was 2.6 fold higher in the mitochondria at 4 h, and 2.5 and 3.3 fold higher in the total liver at 4 h and 6 h, respectively. This faster recovery of GSH, which correlated with greater induction of glutamate-cysteine ligase, attenuated mitochondrial oxidative stress in female mice, as suggested by a lower GSSG/GSH ratio at 6 h (3.8% in males vs. 1.4% in females) and minimal centrilobular nitrotyrosine staining. While c-jun N-terminal kinase (JNK) activation was similar at 2 and 4 h post-APAP, it was 3.1 fold lower at 6 h in female mice. However, female mice were still protected by the JNK inhibitor SP600125. 17β-Estradiol pretreatment moderately decreased liver injury and oxidative stress in male mice without affecting GSH recovery. Conclusion: The lower susceptibility of female mice is achieved by the improved detoxification of reactive oxygen due to accelerated recovery of mitochondrial GSH levels, which attenuates late JNK activation and liver injury. However, even the reduced injury in female mice was still dependent on JNK. While 17β-estradiol partially protects male mice, it does not affect hepatic GSH recovery. - Highlights: • Female mice are less susceptible to acetaminophen overdose than males. • GSH depletion and protein adduct formation are similar in both genders. • Recovery of hepatic GSH levels is faster in females and correlates with Gclc. • Reduced oxidant stress in females leads to reduced JNK activation. • JNK activation and mitochondrial translocation are critical

  3. The gap junction inhibitor 2-aminoethoxy-diphenyl-borate protects against acetaminophen hepatotoxicity by inhibiting cytochrome P450 enzymes and c-jun N-terminal kinase activation

    Energy Technology Data Exchange (ETDEWEB)

    Du, Kuo; Williams, C. David; McGill, Mitchell R.; Xie, Yuchao [Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States); Farhood, Anwar [Department of Pathology, St. David' s North Austin Medical Center, Austin, TX 78756 (United States); Vinken, Mathieu [Department of Toxicology, Center for Pharmaceutical Sciences, Vrije Universiteit Brussels, 1090 Brussels (Belgium); Jaeschke, Hartmut, E-mail: hjaeschke@kumc.edu [Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS (United States)

    2013-12-15

    Acetaminophen (APAP) hepatotoxicity is the leading cause of acute liver failure in the US. Although many aspects of the mechanism are known, recent publications suggest that gap junctions composed of connexin32 function as critical intercellular communication channels which transfer cytotoxic mediators into neighboring hepatocytes and aggravate liver injury. However, these studies did not consider off-target effects of reagents used in these experiments, especially the gap junction inhibitor 2-aminoethoxy-diphenyl-borate (2-APB). In order to assess the mechanisms of protection of 2-APB in vivo, male C56Bl/6 mice were treated with 400 mg/kg APAP to cause extensive liver injury. This injury was prevented when animals were co-treated with 20 mg/kg 2-APB and was attenuated when 2-APB was administered 1.5 h after APAP. However, the protection was completely lost when 2-APB was given 4–6 h after APAP. Measurement of protein adducts and c-jun-N-terminal kinase (JNK) activation indicated that 2-APB reduced both protein binding and JNK activation, which correlated with hepatoprotection. Although some of the protection was due to the solvent dimethyl sulfoxide (DMSO), in vitro experiments clearly demonstrated that 2-APB directly inhibits cytochrome P450 activities. In addition, JNK activation induced by phorone and tert-butylhydroperoxide in vivo was inhibited by 2-APB. The effects against APAP toxicity in vivo were reproduced in primary cultured hepatocytes without use of DMSO and in the absence of functional gap junctions. We conclude that the protective effect of 2-APB was caused by inhibition of metabolic activation of APAP and inhibition of the JNK signaling pathway and not by blocking connexin32-based gap junctions. - Highlights: • 2-APB protected against APAP-induced liver injury in mice in vivo and in vitro • 2-APB protected by inhibiting APAP metabolic activation and JNK signaling pathway • DMSO inhibited APAP metabolic activation as the solvent of 2-APB

  4. Quinacrine induces apoptosis in human leukemia K562 cells via p38 MAPK-elicited BCL2 down-regulation and suppression of ERK/c-Jun-mediated BCL2L1 expression

    Energy Technology Data Exchange (ETDEWEB)

    Changchien, Jung-Jung; Chen, Ying-Jung; Huang, Chia-Hui [Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung 804, Taiwan (China); Cheng, Tian-Lu [Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung 807, Taiwan (China); Lin, Shinne-Ren [Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung 807, Taiwan (China); Chang, Long-Sen, E-mail: lschang@mail.nsysu.edu.tw [Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung 804, Taiwan (China); Department of Biotechnology, Kaohsiung Medical University, Kaohsiung 807, Taiwan (China)

    2015-04-01

    Although previous studies have revealed the anti-cancer activity of quinacrine, its effect on leukemia is not clearly resolved. We sought to explore the cytotoxic effect and mechanism of quinacrine action in human leukemia K562 cells. Quinacrine induced K562 cell apoptosis accompanied with ROS generation, mitochondrial depolarization, and down-regulation of BCL2L1 and BCL2. Upon exposure to quinacrine, ROS-mediated p38 MAPK activation and ERK inactivation were observed in K562 cells. Quinacrine-induced cell death and mitochondrial depolarization were suppressed by the p38MAPK inhibitor SB202190 and constitutively active MEK1 over-expression. Activation of p38 MAPK was shown to promote BCL2 degradation. Further, ERK inactivation suppressed c-Jun-mediated transcriptional expression of BCL2L1. Over-expression of BCL2L1 and BCL2 attenuated quinacrine-evoked mitochondrial depolarization and rescued the viability of quinacrine-treated cells. Taken together, our data indicate that quinacrine-induced K562 cell apoptosis is mediated through mitochondrial alterations triggered by p38 MAPK-mediated BCL2 down-regulation and suppression of ERK/c-Jun-mediated BCL2L1 expression. - Highlights: • Quinacrine induces K562 cell apoptosis via down-regulation of BCL2 and BCL2L1. • Quinacrine induces p38 MAPK activation and ERK inactivation in K562 cells. • Quinacrine elicits p38 MAPK-mediated BCL2 down-regulation. • Quinacrine suppresses ERK/c-Jun-mediated BCL2L1 expression.

  5. Estrogen receptor alpha, fos-related antigen-2, and c-Jun coordinately regulate human UDP glucuronosyltransferase 2B15 and 2B17 expression in response to 17beta-estradiol in MCF-7 cells.

    Science.gov (United States)

    Hu, Dong Gui; Mackenzie, Peter I

    2009-08-01

    UDP-glucuronosyltransferase 2B15 and 2B17 expression is up-regulated by 17beta-estradiol in MCF-7 breast cancer cells, as assessed by quantitative real-time polymerase chain reaction. Using 5'-deletion mapping and site-directed mutagenesis, we demonstrate that 17beta-estradiol activation of UGT2B15 gene transcription is mediated by a 282-base pair fragment positioned -454 to -172 nucleotides from the translation start site. This region contains two putative activator protein-1 (AP-1) elements, one imperfect estrogen response element (ERE), and two consensus ERE half-sites. We propose that these five sites act as an estrogen response unit (ERU), because mutation in any site reduces activation of the UGT2B15 promoter by 17beta-estradiol. Despite the presence of two AP-1 elements, the UGT2B15 promoter is not responsive to the AP-1 activator phorbol 12-myristate 13-acetate. Although electrophoretic mobility shift assays (EMSA) indicate that the AP-1 proteins c-Jun and Fos-related antigen 2 (Fra-2) bound to the distal AP-1 site, binding of Jun or Fos family members to the proximal AP-1 site was not detected by EMSA. Chromatin immunoprecipitation assays showed a 17beta-estradiol-induced recruitment of estrogen receptor (ER) alpha, c-Jun, and Fra-2 to the 282-bp ERU. The involvement of these three transcription factors in the stimulation of UGT2B15 gene expression by 17beta-estradiol was confirmed by siRNA silencing experiments. Mutagenesis and siRNA experiments indicate that UGT2B17 expression is also regulated by 17beta-estradiol via the ERU, which is fully conserved in both promoters. Because UGT2B15 and UGT2B17 inactivate steroid hormones by glucuronidation, the regulation of their genes by 17beta-estradiol may maintain steroid hormone homeostasis and prevent excessive estrogen signaling activity.

  6. Inhibition of vein graft stenosis with a c-jun targeting DNAzyme in a cationic liposomal formulation containing 1,2-dioleoyl-3-trimethylammonium propane (DOTAP)/1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE).

    Science.gov (United States)

    Li, Yue; Bhindi, Ravinay; Deng, Zhou J; Morton, Stephen W; Hammond, Paula T; Khachigian, Levon M

    2013-10-09

    Coronary artery bypass grafting (CABG) is among the most commonly performed heart surgical procedures. Saphenous vein graft failure due to stenosis impedes the longer-term success of CABG. A key cellular event in the process of vein graft stenosis is smooth muscle cell hyperplasia. In this study, we evaluated the effect of a DNAzyme (Dz13) targeting the transcription factor c-Jun in a rabbit model of vein graft stenosis in a cationic liposomal formulation containing 1,2-dioleoyl-3-trimethylammonium propane (DOTAP)/1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE). Dz13 in DOTAP/DOPE has undergone preclinical toxicological testing, and a Phase I clinical trial we recently conducted in basal cell carcinoma cancer patients demonstrates that it is safe and well tolerated after local administration. Effects of Dz13 in a formulation containing DOTAP/DOPE on smooth muscle cell (SMC) growth and c-Jun expression were assessed. Dz13 transfection was determined by cellular uptake of carboxyfluorescein-labeled Dz13. Autologous jugular vein to carotid artery transplantation was performed in New Zealand White rabbits to investigate the effect of the Dz13 in DOTAP/DOPE formulation on intimal hyperplasia. Dz13/DOTAP/DOPE reduced SMC proliferation and c-Jun protein expression in vitro compared with an impotent form of Dz13 bearing a point mutation in its catalytic domain (Dz13.G>C). The Dz13(500 μg)/DOTAP/DOPE formed lipoplexes that were colloidally stable for up to 1h on ice (0°C) and 30 min at 37°C, allowing sufficient uptake by the veins. Dz13 (500 μg) inhibited neointima formation 28 d after end-to-side transplantation. This formulation applied to veins prior to transplantation may potentially be useful in efforts to reduce graft failure. © 2013.

  7. Dimerumic Acid Inhibits SW620 Cell Invasion by Attenuating H2O2-Mediated MMP-7 Expression via JNK/C-Jun and ERK/C-Fos Activation in an AP-1-Dependent Manner

    Directory of Open Access Journals (Sweden)

    Bing-Ying Ho, Yao-Ming Wu, King-Jen Chang, Tzu-Ming Pan

    2011-01-01

    Full Text Available Reactive oxygen species (ROS such as hydrogen peroxide (H2O2 in the tumor microenvironment play important roles in tumor invasion and metastasis. Recently, ROS have been reported to cause a significant increase in the production and expression of matrix metalloproteinase (MMP-7, which is closely correlated with metastatic colorectal cancer. The present study was undertaken to evaluate the scavenging activity of dimerumic acid (DMA for H2O2 isolated from Monascus-fermented rice to investigate the inhibitory effects of DMA on the invasive potential of SW620 human colon cancer cells, and to explore the mechanisms underlying both these phenomena. Our results showed that increased MMP-7 expression due to H2O2 exposure was mediated by activation of mitogen-activated protein kinases (MAPKs such as Jun N-terminal kinase (JNK, extracellular-regulated kinase (ERK, and p38 kinase. DMA pretreatment suppressed activation of H2O2-mediated MAPK pathways and cell invasion. Moreover, H2O2-triggered MMP-7 production was demonstrated via JNK/c-Jun and ERK/c-Fos activation in an activating protein 1 (AP-1-dependent manner. Taken together, these results suggest that DMA suppresses H2O2-induced cell invasion by inhibiting AP-1-mediated MMP-7 gene transcription via the JNK/c-Jun and ERK/c-Fos signaling pathways in SW620 human colon cancer cells. Our data suggest that DMA may be useful in minimizing the development of colorectal metastasis. In the future, DMA supplementation may be a beneficial antioxidant to enhance surgical outcomes.

  8. Effects of RSM and astragus on expression of Fos and Jun proteins in rat brains after cerebral ischemia and reperfusion%丹参、黄芪合用对脑缺血再灌注后脑组织Fos,Jun蛋白表达的影响

    Institute of Scientific and Technical Information of China (English)

    曲友直; 高国栋; 赵燕玲

    2003-01-01

    AIM: To investigate the expression of Fos and Jun proteins in rat brainsafter focal cerebral ischemia followed by reperfusion and effects of RSMand astragus. METHODS: 30 SD adult male rats were divided into 5groups at random . Group A: sham-operated group; Group B: model group;Group C: treated with RSM; Group D: treated with astragus; Group E:treated with RSM and astragus. The immunohistochemistry and medicalimage processing system(MIPS) were used to measure the numbers andmean grey levels of Fos and Jun protein positive cells in rat cerebralcortex of 5 groups. RESULTS: ( 1 ) In cerebral cortex of group B , C , D, E, the numbers of Fos and Jun positive cells were more than those ingroup A and mean grey levels of Fos and Jun positive cells were lower thanthose in group A(P < 0.01); (2) In cerebral cortex of ischemic sidesin group C, D, E,the numbers of Fos and Jun positive cells were less thanthose in group B and mean grey levels of Fos and Jun positive cells werehigher than those in group B(P < 0.01) ; (3) Group E had more sig-nificant effects than group C or group D ( P < 0. 01 ). CONCLUSION:The expression of Fos protein and Jun protein in model group increasedsignificantly, compared with sham-operated group; RSM , astragus , RSMand astragus all could inhibit partly the expression of Fos protein and Junprotein after cerebral ischemia and reperfusion; Prescription of RSM andastragus had stronger inhibiting effects than RSM or astragus. It may be oneof mechanisms that ischemic stoke is treated by reinforcing Qi and acti-vating blood circulation therapy in TCM clinic.

  9. New Study Says CAI May Favor Introverts.

    Science.gov (United States)

    Hopmeier, George

    1981-01-01

    A personality research study using the Myers-Briggs Type Indicator indicates that computer-assisted instruction programs favor introverts, i.e., those learners who can concentrate on details, memorize facts, and stay with a task until it is completed. (JJD)

  10. Compupoem: CAI for Writing and Studying Poetry.

    Science.gov (United States)

    Marcus, Stephen

    1982-01-01

    Describes a computer program that prompts the user for different parts of speech and formats the words in a haiku-like poetic structure. (Available from "The Computing Teacher," Department of Computer and Information Science, University of Oregon, Eugene, OR 97403.) (AEA)

  11. Computer Assisted Instruction (CAI) in Language Teaching

    Institute of Scientific and Technical Information of China (English)

    Xin; Jing

    2015-01-01

    There are many ways to use computers for English language teaching.First of all,teachers can use them to prepare for classes.They can use a word processing program to write teaching materials and tests.They can use dictionaries,encyclopedias,et c.,available on the computer as resources to help them prepare

  12. Strategies for Production and Dissemination of CAI.

    Science.gov (United States)

    Olivier, W. P.; Scott, G. F.

    The Individualization Project at the Ontario Institute for Studies in Education (OISE) was organized on a cooperative basis with a federal agency and several community colleges. The main design goals were to produce needed courseware, move smoothly from research and development to a production mode of operation, and to emphasize dissemination of…

  13. Design Guidelines for CAI Authoring Systems.

    Science.gov (United States)

    Hunka, S.

    1989-01-01

    Discussion of the use of authoring systems for courseware development focuses on guidelines to be considered when designing authoring systems. Topics discussed include allowing a variety of instructional strategies; interaction with peripheral processes such as student records; the editing process; and human factors in computer interface design,…

  14. Tumor Necrosis Factor-α and Apoptosis Signal-Regulating Kinase 1 Control Reactive Oxygen Species Release, Mitochondrial Autophagy and C-Jun N-Terminal Kinase/P38 Phosphorylation During Necrotizing Enterocolitis

    Directory of Open Access Journals (Sweden)

    Naira Baregamian

    2009-01-01

    Full Text Available Background: Oxidative stress and inflammation may contribute to the disruption of the protective gut barrier through various mechanisms; mitochondrial dysfunction resulting from inflammatory and oxidative injury may potentially be a significant source of apoptosis during necrotizing enterocolitis (NEC. Tumor necrosis factor (TNFα is thought to generate reactive oxygen species (ROS and activate the apoptosis signal-regulating kinase 1 (ASK1-c-Jun N-terminal kinase (JNK/p38 pathway. Hence, the focus of our study was to examine the effects of TNFα/ROs on mitochondrial function, ASK1-JNK/p38 cascade activation in intestinal epithelial cells during NEC.

  15. La Eximente de miedo insuperable en el código penal peruano de 1991, su aplicación por los juzgados y salas penales de Junín

    OpenAIRE

    Paredes Vargas, César Augusto

    2002-01-01

    Durante nuestros estudios doctorales, hemos desarrollado la tesis que ahora sometemos a la opinión de los Profesores integrantes de la Comisión Revisora. El trabajo de investigación ha abarcado, la verificación y procesamiento de sentencias judiciales relativas a una causal de exención nueva en nuestro Código, circunscrita al obrar compelido por miedo insuperable de un mal igual o mayor, conforme al Art. 20.7 del Código Penal de 1991, pronunciadas en la Corte Superior de Junín y contrastad...

  16. Roles of PI3K/Akt and c-Jun signaling pathways in human papillomavirus type 16 oncoprotein-induced HIF-1α, VEGF, and IL-8 expression and in vitro angiogenesis in non-small cell lung cancer cells.

    Directory of Open Access Journals (Sweden)

    Erying Zhang

    Full Text Available Human papillomavirus (HPV-16 infection may be related to non-smoking associated lung cancer. Our previous studies have found that HPV-16 oncoproteins promoted angiogenesis via enhancing hypoxia-inducible factor-1α (HIF-1α, vascular endothelial growth factor (VEGF, and interleukin-8 (IL-8 expression in non-small cell lung cancer (NSCLC cells. In this study, we further investigated the roles of PI3K/Akt and c-Jun signaling pathways in it.Human NSCLC cell lines, A549 and NCI-H460, were stably transfected with pEGFP-16 E6 or E7 plasmids. Western blotting was performed to analyze the expression of HIF-1α, p-Akt, p-P70S6K, p-P85S6K, p-mTOR, p-JNK, and p-c-Jun proteins. VEGF and IL-8 protein secretion and mRNA levels were determined by ELISA and Real-time PCR, respectively. The in vitro angiogenesis was observed by human umbilical vein endothelial cells (HUVECs tube formation assay. Co-immunoprecipitation was performed to analyze the interaction between c-Jun and HIF-1α.HPV-16 E6 and E7 oncoproteins promoted the activation of Akt, P70S6K, P85S6K, mTOR, JNK, and c-Jun. LY294002, a PI3K inhibitor, inhibited HPV-16 oncoprotein-induced activation of Akt, P70S6K, and P85S6K, expression of HIF-1α, VEGF, and IL-8, and in vitro angiogenesis. c-Jun knockdown by specific siRNA abolished HPV-16 oncoprotein-induced HIF-1α, VEGF, and IL-8 expression and in vitro angiogenesis. Additionally, HPV-16 oncoproteins promoted HIF-1α protein stability via blocking proteasome degradation pathway, but c-Jun knockdown abrogated this effect. Furthermore, HPV-16 oncoproteins increased the quantity of c-Jun binding to HIF-1α.PI3K/Akt signaling pathway and c-Jun are involved in HPV-16 oncoprotein-induced HIF-1α, VEGF, and IL-8 expression and in vitro angiogenesis. Moreover, HPV-16 oncoproteins promoted HIF-1α protein stability possibly through enhancing the interaction between c-Jun and HIF-1α, thus making a contribution to angiogenesis in NSCLC cells.

  17. Experiment study of effect of Valeriana officinalis var. latifolia on expression of C-Fos, C-Jun in hippocampus zone after focal cerebral ischemia%宽叶缬草对局灶性脑缺血后海马区C-Fos,C-Jun表达的实验研究

    Institute of Scientific and Technical Information of China (English)

    王云甫; 严洁; 黄朝芬; 何国厚

    2003-01-01

    AIM: To study influence of Valeriana officinalis var. latifolia(VOL) on expression of C-Fos, C-Jun after focal cerebral ischemia. METHODs: Inducing rat model of reversible middle cerebral artery occlusion(MCAO) using Koizumi' s intraluminal suture occlusion method. 48 male rats were divided into 5 groups randomly, pseudo-operation group, MCAO group, saline control group, VOL group. 2 hours after MCAO, we took gastric gavage with VOL and saline, 8 hour per time, and took out of brain to test C-Fos, C-Jun expression immunohistochemically at the 5th day after oper-ation. RESULTS: There was no positive cell in each hippocampus zone of ormal group; we observed C-Fos, C-Jun positive cells in each Hip-pocampus zone after MCAO; Density of C-Fos, C-Jun positive cells of VOL group were apparently lower than that of simple ischemia group. CON CLUSION: VOL can relieve histopathological lesions after cerebral is-chemia and promote protection function of rat through inhibiting the ex-pression of C-Fos, C-Jun expression.

  18. 转录因子c-fos/c-jun调控成釉细胞基质金属蛋白酶20基因的表达%c-fos/c-jun regulates extracellular matrix metalloproteinase 20 expression in ameloblasts

    Institute of Scientific and Technical Information of China (English)

    唐培娟; 王长磊; 宫春梅; 唐培倩; 郝建忠

    2015-01-01

    BACKGROUND:Matrix metaloproteinase 20 is a protease specificaly expressed in ameloblasts, which has an important role in dental enamel development. To study the regulatory mechanisms for matrix metaloproteinase 20 at the molecular level lays the foundation for further animal experiments. OBJECTIVE:To explore the regulatory effects of transcription factor c-fos/c-jun for matrix metaloproteinase 20 in mouse ameloblasts and to preliminarily confirm the role of c-fos/c-jun in enamel development. METHODS:First of al, a recombinant plasmid containing c-fos was established, and then dual-luciferase reporter assay system and RT-PCR were used to analyze the effects of c-fos, c-jun transfection of ameloblasts on the activity of matrix metaloproteinase 20. Furthermore, the effect of c-fos, c-jun on matrix metaloproteinase 20 was explored based on gene site-directed mutation and dual-luciferase reporter assay system. RESULTS AND CONCLUSION:Double luciferase report assay system and RT-PCR analysis showed that the mRNA expression of matrix metaloproteinase-20 was significantly upregulated after c-fos, c-jun transfection of ameloblasts, but c-fos/c-jun could not upregulate the transcriptional activity of matrix metaloproteinase 20 promoter when mutation occurred at AP1 binging site. These findings indicate that c-fos/c-jun has significant effects in regulating the mRNA expression of matrix metaloproteinase 20, which shows c-fos/c-jun plays an important biological meaning in enamel development.%背景:基质金属蛋白酶20是在成釉细胞中特异性表达的一种蛋白酶,其在牙齿釉质发育过程中具有重要作用。从分子角度研究基质金属蛋白酶20可受到的调控机制,为进一步做动物实验奠定基础。目的:通过研究转录因子c-fos/c-jun对小鼠成釉细胞基质金属蛋白酶20基因的调控作用,初步确定c-fos/c-jun在牙釉质发育中的作用。方法:首先构建 c-fos 真核表达载体重组质粒,分别利

  19. H-ras transfection of the rat kidney cell line NRK-52E results in increased induction of c-fos, c-jun and hsp70 following sulofenur treatment.

    Science.gov (United States)

    Gu, H; Smith, M W; Phelps, P C; Berezesky, I K; Merriman, R L; Boder, G B; Trump, B F

    1996-09-10

    The effect of the antineoplastic drug sulofenur on the induction of the immediate-early genes (IEG) c-fos and c-jun and the stress gene hsp70 was compared in the rat kidney epithelial-like cell line NRK-52E and a derivative H-ras-transfected (H/1.2NRK-52E) cell line. Fold induction for each gene after sulofenur (500 microM) treatment was greater in H/1.2NRK-52E. The maximum increases for NRK-2E and H/1.2NRK-52E were as follows: c-fos, approximately 10-fold and approximately 18-fold; c-jun, approximately 2.5-fold and approximately 3.6-fold; hsp70, approximately 13-fold and approximately 30-fold. In cells loaded with EGTA/AM or treated in low or no Ca2+ HBSS, c-fos induction was reduced similarly in both cell types. However, inhibition of protein kinases with staurosporin and calphostin C reduced c-fos by 80% in NRK-52E but by only 10-20% in H/1.2NRK.52E. These results indicate that sulofenur-induced IEG elevation is Ca(2+)-dependent and that the requirement for protein kinase C activation is bypassed in H-ras-transfected cells.

  20. Expression and significance of c-Jun N-terminal protein kinase 1/2 protein in chronic hibernated myocardium of domestic pigs%家猪慢性冬眠心肌中C-Jun N末端蛋白激酶1/2蛋白的表达及意义

    Institute of Scientific and Technical Information of China (English)

    李东野; 朱红; 夏勇; 潘德峰; 杨煜; 李雷; 祁春梅

    2005-01-01

    背景:急性心肌缺血时c-Jun N末端蛋白激酶(c-Jun N-terminal protein kinase,JNK)被激活,并使得缺血损伤加重.慢性冬眠心肌组织中JNK的亚型--JNK1/2是否被激活及其在慢性冬眠心肌发生发展机制中的作用又是什么呢?目的:明确慢性冬眠心肌组织中JNK1/2的蛋白表达及其磷酸化(p-JNK1/2)的变化.设计:随机对照的实验研究.单位:徐州医学院附属医院心血管病研究所.材料和方法:在徐州医学院附属医院导管室进行动物模型的制备、在徐州医学院生化教研室测定JNK1/2的蛋白表达及其磷酸化(p-JNK1/2)的变化.将14只小型中国家猪随机分为实验组(n=8)与对照组(n=6).实验组以右冠状动脉为靶血管,经右股动脉送入自制的缩窄器,制备成慢性冬眠心肌及心肌梗死的模型.获取对照组心肌组织、实验组中的正常心肌组织及慢性冬眠心肌组织的样本进行光镜、电镜检查并采用免疫印迹(Western blotting)分析3组心肌组织的JNK1/2的蛋白表达及其磷酸化的变化.主要观察指标:慢性冬眠心肌组织中JNK1/2是否被活化.结果:实验组慢性冬眠心肌组织p-JNK1/2比实验组正常心肌组织、对照组心肌组织高.对照组、实验组正常心肌组织、实验组慢性冬眠心肌组织p-JNK1/2的免疫活性分别为1,1.42±0.52,2.6±0.59.结论:慢性冬眠心肌组织中JNK1/2被激活,并参与了慢性冬眠心肌的发生和发展.%BACKGROUND: Acute myocardial ischemia can activate the c-Jun N-terminal protein kinase(JNK) and, in turn, the ischemia damage can be aggravated by JNK. While in chronic hibernating myocardium, whether chronic myocardial ischemia can activate JNK1/2 or not and what is the role of JNK1/2 in developing the chronic hibernating myocardium, is not clear.OBJECTIVE :To identify protein expression of JNK1/2 and the p-JNK1/2 changes in chronic hibernating myocardium.DESIGN: Randomly controlled experimental research.SETTING: This