Tor-Tor Sebagai Properti Dan Perwujudan Adat

OpenAIRE

Frida Deliana Harahap

2009-01-01

Tulisan ini mendeskripsikan tor?tor Angkola. Tor?tor adalah tarian adat  yang dipergunakan dalam upacara adat nagodang (adat besar), sehingga pertunjukan tor?tor  dalam upacara adat haruslah bersumber dari adat Angkola itu sendiri.  Ada dua aspek yang akan dibicarakan dalam tulisan ini:  yang pertama mengenai aspek koreografi yang juga meliputi olah gerak tubuh;  kedua, aspek tata busana penari saat melakukan pertunjukan tor?tor.   etn-sep2005-6...

Enhancing mTOR-targeted cancer therapy by preventing mTOR/raptor inhibition-initiated, mTOR/rictor-independent Akt activation

OpenAIRE

Wang, Xuerong; Yue, Ping; Kim, Young Ae; Fu, Haian; Khuri, Fadlo R.; Sun, Shi-Yong

2008-01-01

It has been shown that mTOR inhibitors activate Akt while inhibiting mTOR signaling. However, the underlying mechanisms and the impact of the Akt activation on mTOR-targeted cancer therapy are unclear. The present work focused on addressing the role of mTOR/rictor in mTOR inhibitor-induced Akt activation and the impact of sustained Akt activation on mTOR-targeted cancer therapy. Thus, we have demonstrated that mTOR inhibitors increase Akt phosphorylation through a mechanism independent of mTO...

The TorR High-Affinity Binding Site Plays a Key Role in Both torR Autoregulation and torCAD Operon Expression in Escherichia coli

OpenAIRE

Ansaldi, Mireille; Simon, Gwénola; Lepelletier, Michèle; Méjean, Vincent

2000-01-01

In the presence of trimethylamine N-oxide (TMAO), the TorS-TorR two-component regulatory system induces the torCAD operon, which encodes the TMAO respiratory system of Escherichia coli. The sensor protein TorS detects TMAO and transphosphorylates the response regulator TorR which, in turn, activates transcription of torCAD. The torR gene and the torCAD operon are divergently transcribed, and the short torR-torC intergenic region contains four direct repeats (the tor boxes) which proved to be ...

TOR1 and TOR2 Have Distinct Locations in Live Cells▿ †

OpenAIRE

Sturgill, Thomas W.; Cohen, Adiel; Diefenbacher, Melanie; Trautwein, Mark; Martin, Dietmar E.; Hall, Michael N.

2008-01-01

TOR is a structurally and functionally conserved Ser/Thr kinase found in two multiprotein complexes that regulate many cellular processes to control cell growth. Although extensively studied, the localization of TOR is still ambiguous, possibly because endogenous TOR in live cells has not been examined. Here, we examined the localization of green fluorescent protein (GFP) tagged, endogenous TOR1 and TOR2 in live S. cerevisiae cells. A DNA cassette encoding three copies of green fluorescent pr...

Torness. Keep it green

International Nuclear Information System (INIS)

Flood, M.

1979-01-01

The subject is discussed under the following headings: Torness foolishness (concerning the steps being taken towards constructing a nuclear power station at Torness Point in East Lothian, Scotland); the case against Torness (a summary); is Torness necessary (discusses the present, planned and forecast positions of electricity supply and demand in Scotland); how much will Torness cost, and who will pay; the local impact of Torness (on employment, infrastructure, amenity and future prospects); how reliable is the Advanced Gas Cooled Reactor (the choice of the AGR type reactor and discussions on the 'Hinkley Point incident' and the 'Hunterston incident'); how safe is nuclear power (discussion on AGR programme, nuclear accidents, sabotage, war, nuclear waste, plutonium, secrecy and security); public opposition to Torness; what can be done. (U.K.)

TOR1 and TOR2 are structurally and functionally similar but not identical phosphatidylinositol kinase homologues in yeast

OpenAIRE

Helliwell, S. B.; Wagner, P.; Kunz, J.; Deuter-Reinhard, M.; Henriquez, R.; Hall, M. N.

1994-01-01

The Saccharomyces cerevisiae genes TOR1 and TOR2 were originally identified by mutations that confer resistance to the immunosuppressant rapamycin. TOR2 was previously shown to encode an essential 282-kDa phosphatidylinositol kinase (PI kinase) homologue. The TOR1 gene product is also a large (281 kDa) PI kinase homologue, with 67% identity to TOR2. TOR1 is not essential, but a TOR1 TOR2 double disruption uniquely confers a cell cycle (G1) arrest as does exposure to rapamycin; disruption of T...

Viral factor TAV recruits TOR/S6K1 signalling to activate reinitiation after long ORF translation

Science.gov (United States)

Schepetilnikov, Mikhail; Kobayashi, Kappei; Geldreich, Angèle; Caranta, Carole; Robaglia, Christophe; Keller, Mario; Ryabova, Lyubov A

2011-01-01

The protein kinase TOR (target-of-rapamycin) upregulates translation initiation in eukaryotes, but initiation restart after long ORF translation is restricted by largely unknown pathways. The plant viral reinitiation factor transactivator–viroplasmin (TAV) exceptionally promotes reinitiation through a mechanism involving retention on 80S and reuse of eIF3 and the host factor reinitiation-supporting protein (RISP) to regenerate reinitiation-competent ribosomal complexes. Here, we show that TAV function in reinitiation depends on physical association with TOR, with TAV–TOR binding being critical for both translation reinitiation and viral fitness. Consistently, TOR-deficient plants are resistant to viral infection. TAV triggers TOR hyperactivation and S6K1 phosphorylation in planta. When activated, TOR binds polyribosomes concomitantly with polysomal accumulation of eIF3 and RISP—a novel and specific target of TOR/S6K1—in a TAV-dependent manner, with RISP being phosphorylated. TAV mutants defective in TOR binding fail to recruit TOR, thereby abolishing RISP phosphorylation in polysomes and reinitiation. Thus, activation of reinitiation after long ORF translation is more complex than previously appreciated, with TOR/S6K1 upregulation being the key event in the formation of reinitiation-competent ribosomal complexes. PMID:21343906

Testing Torness

International Nuclear Information System (INIS)

Roche, P.

1987-01-01

Fueling of the Torness-1 reactor began in July, 1987, about a year behind schedule. The main reason for the delay was the discovery of a design weakness in the control rods. This has now been put right. The Industrial Pollution Inspectorate has authorized the discharge of small quantities of liquid and gaseous radioactive waste. The need to grant this so long before the station is ready to make discharges is questioned. The actual level of discharge allowed is also a focus of criticism. The political consequences of the Torness debate is seen as the loss of seats by the Conservative party in Scotland in the General Election. More problems are foreseen for Torness over discharges and evacuation plans. (UK)

Development and characterization of cell culture systems from Puntius (Tor) chelynoides (McClelland).

Science.gov (United States)

Goswami, M; Sharma, B S; Tripathi, A K; Yadav, Kamalendra; Bahuguna, S N; Nagpure, N S; Lakra, W S; Jena, J K

2012-05-25

Puntius (Tor) chelynoides, commonly known as dark mahseer, is a commercially important coldwater fish species which inhabits fast-flowing hill-streams of India and Nepal. Cell culture systems were developed from eye, fin, heart and swim bladder tissues of P. chelynoides using explant method. The cell culture system developed from eye has been maintained towards a continuous cell line designated as PCE. The cells were grown in 25cm(2) tissue culture flasks with Leibovitz' L-15 media supplemented with 20 % fetal bovine serum (FBS) at 24°C. The PCE cell line consists of predominantly fibroblast-like cells and showed high plating efficiency. The monolayer formed from the fin and heart explants were comprised of epithelial as well as fibroblast-like cells, a prominent and rhythmic heartbeat was also observed in heart explants. Monolayer formed from swim bladder explants showed the morphology of fibroblast-like cells. All the cells from different tissues are able to grow at an optimum temperature of 24°C and growth rate increased as the FBS concentration increased. The PCE cell line was characterized using amplification of mitochondrial cytochrome oxidase subunit I (COI) & 16S rRNA genes which confirmed that the cell line originated from P. chelynoides. Cytogenetic analysis of PCE cell line and cells from fin revealed a diploid count of 100 chromosomes. Upon transfection with pEGFP-C1 plasmid, bright fluorescent signals were observed, suggesting that this cell line can be used for transgenic and genetic manipulation studies. Further, genotoxicity assessment of PCE cells illustrated the utility of this cell line as an in vitro model for aquatic toxicological studies. The PCE cell line was successfully cryopreserved and revived at different passage levels. The cell line and culture systems are being maintained to develop continuous cell lines for further studies. Copyright © 2012 Elsevier B.V. All rights reserved.

Transportable gamma backscattering TOR-3 gauge

International Nuclear Information System (INIS)

Lakhmanov, P.G.; Skoblo, Yu.A.; Timofeev, V.B.

1976-01-01

A portable reflection gamma thickness meter TOR-3 is described having a greater measurement accuracy and wider operation temperature interval as compared to earlier serial instrument TOR-1. Integrated circuits are used in the TOR-3 construction. The principal electric diagram and technical characteristics of TOR-3 are presented

Towards Predicting Efficient and Anonymous Tor Circuits

OpenAIRE

Barton, Armon; Imani, Mohsen; Ming, Jiang; Wright, Matthew

2018-01-01

The Tor anonymity system provides online privacy for millions of users, but it is slower than typical web browsing. To improve Tor performance, we propose PredicTor, a path selection technique that uses a Random Forest classifier trained on recent measurements of Tor to predict the performance of a proposed path. If the path is predicted to be fast, then the client builds a circuit using those relays. We implemented PredicTor in the Tor source code and show through live Tor experiments and Sh...

Comparative proteomics of a tor inducible Aspergillus fumigatus mutant reveals involvement of the Tor kinase in iron regulation.

Science.gov (United States)

Baldin, Clara; Valiante, Vito; Krüger, Thomas; Schafferer, Lukas; Haas, Hubertus; Kniemeyer, Olaf; Brakhage, Axel A

2015-07-01

The Tor (target of rapamycin) kinase is one of the major regulatory nodes in eukaryotes. Here, we analyzed the Tor kinase in Aspergillus fumigatus, which is the most important airborne fungal pathogen of humans. Because deletion of the single tor gene was apparently lethal, we generated a conditional lethal tor mutant by replacing the endogenous tor gene by the inducible xylp-tor gene cassette. By both 2DE and gel-free LC-MS/MS, we found that Tor controls a variety of proteins involved in nutrient sensing, stress response, cell cycle progression, protein biosynthesis and degradation, but also processes in mitochondria, such as respiration and ornithine metabolism, which is required for siderophore formation. qRT-PCR analyses indicated that mRNA levels of ornithine biosynthesis genes were increased under iron limitation. When tor was repressed, iron regulation was lost. In a deletion mutant of the iron regulator HapX also carrying the xylp-tor cassette, the regulation upon iron deprivation was similar to that of the single tor inducible mutant strain. In line, hapX expression was significantly reduced when tor was repressed. Thus, Tor acts either upstream of HapX or independently of HapX as a repressor of the ornithine biosynthesis genes and thereby regulates the production of siderophores. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Evolution of the TOR Pathway.

NARCIS (Netherlands)

Dam, T.J.P. van; Zwartkruis, F.J.; Bos, J.L.; Snel, B.

2011-01-01

The TOR kinase is a major regulator of growth in eukaryotes. Many components of the TOR pathway are implicated in cancer and metabolic diseases in humans. Analysis of the evolution of TOR and its pathway may provide fundamental insight into the evolution of growth regulation in eukaryotes and

Torness: proposed nuclear power station

International Nuclear Information System (INIS)

Anon.

1979-01-01

The need for and desirability of nuclear power, and in particular the proposed nuclear power station at Torness in Scotland, are questioned. Questions are asked, and answered, on the following topics: position, appearance and cost of the proposed Torness plant, and whether necessary; present availability of electricity, and forecast of future needs, in Scotland; energy conservation and alternative energy sources; radiation hazards from nuclear power stations (outside, inside, and in case of an accident); transport of spent fuel from Torness to Windscale; radioactive waste management; possibility of terrorists making a bomb with radioactive fuel from a nuclear power station; cost of electricity from nuclear power; how to stop Torness. (U.K.)

Hypothalamic mTOR signaling regulates food intake.

Science.gov (United States)

Cota, Daniela; Proulx, Karine; Smith, Kathi A Blake; Kozma, Sara C; Thomas, George; Woods, Stephen C; Seeley, Randy J

2006-05-12

The mammalian Target of Rapamycin (mTOR) protein is a serine-threonine kinase that regulates cell-cycle progression and growth by sensing changes in energy status. We demonstrated that mTOR signaling plays a role in the brain mechanisms that respond to nutrient availability, regulating energy balance. In the rat, mTOR signaling is controlled by energy status in specific regions of the hypothalamus and colocalizes with neuropeptide Y and proopiomelanocortin neurons in the arcuate nucleus. Central administration of leucine increases hypothalamic mTOR signaling and decreases food intake and body weight. The hormone leptin increases hypothalamic mTOR activity, and the inhibition of mTOR signaling blunts leptin's anorectic effect. Thus, mTOR is a cellular fuel sensor whose hypothalamic activity is directly tied to the regulation of energy intake.

PeerFlow: Secure Load Balancing in Tor

Directory of Open Access Journals (Sweden)

Johnson Aaron

2017-04-01

Full Text Available We present PeerFlow, a system to securely load balance client traffic in Tor. Security in Tor requires that no adversary handle too much traffic. However, Tor relays are run by volunteers who cannot be trusted to report the relay bandwidths, which Tor clients use for load balancing. We show that existing methods to determine the bandwidths of Tor relays allow an adversary with little bandwidth to attack large amounts of client traffic. These methods include Tor’s current bandwidth-scanning system, TorFlow, and the peer-measurement system EigenSpeed. We present an improved design called PeerFlow that uses a peer-measurement process both to limit an adversary’s ability to increase his measured bandwidth and to improve accuracy. We show our system to be secure, fast, and efficient. We implement PeerFlow in Tor and demonstrate its speed and accuracy in large-scale network simulations.

A TorPath to TorCoin: Proof-of-Bandwidth Altcoins for Compensating Relays

Science.gov (United States)

2014-07-18

TorCoin by checking the blockchain . Report Documentation Page Form ApprovedOMB No. 0704-0188 Public reporting burden for the collection of...of occasional colluding circuits, TorCoin also limits the number of coins each circuit can mine. This coin number is included in the blockchain , so it

The Malaysian Intermodal Terminal System: The Implication on the Malaysian Maritime Cluster

Directory of Open Access Journals (Sweden)

Mohamad Rosni Othman

2016-06-01

Full Text Available The maritime sector in Malaysia is best known globally due to the Straits of Malacca and being a nation surrounded by sea. Malaysia also has a substantial maritime industry consisting of numerous shipyards, ports and terminal faculties, ship services and a plethora of other companies and institutions with maritime oriented activities and become essential components of the Malaysia's maritime clusters. Issues such as underutilised intermodal terminals, uneven proportions in the freight transport infrastructure and road and seaport congestions prevent Malaysian seaports from achieving their full potential in serving their respective hinterlands. The key factors to improve Malaysian dry port or intermodal terminals are transport network; container planning; competition; location and, externalities. The paper does not only present the critical challenges faced by Malaysian intermodal terminals especially dry ports and the implications for seaport competency but it also provides strategies to utilise the Malaysian freight multimodal system to amplify seaports
tm performance in serving their hinterlands. As such, this may warrant policy makers to devise a comprehensive national master plan for the maritime sector in order for Malaysia to further develop her maritime industry and economies.

The prognostic role of mTOR and p-mTOR for survival in non-small cell lung cancer: a systematic review and meta-analysis.

Directory of Open Access Journals (Sweden)

Lei Li

Full Text Available The mammalian target of rapamycin (mTOR and phosphorylated mTOR (p-mTOR are potential prognostic markers and therapeutic targets for non-small cell lung cancer (NSCLC. However, the association between mTOR/p-mTOR expression and NSCLC patients' prognosis remains controversial. Thus, a meta-analysis of existing studies evaluating the prognostic role of mTOR/p-mTOR expression for NSCLC was conducted.A systemically literature search was performed via Pubmed, Embase, Medline as well as CNKI (China National Knowledge Infrastructure. Studies were included that reported the hazard ratio (HR and 95%CI for the association between mTOR/p-mTOR expression and NSCLC patients' survival. Random-effects model was used to pool HRs.Ten eligible studies were included in this meta-analysis, with 4 about m-TOR and 7 about p-mTOR. For mTOR, the pooled HR of overall survival (OS was 1.00 (95%CI 0.5 to 1.99 by univariate analysis and 1.22 (95%CI 0.53 to 2.82 by multivariate analysis. For p-mTOR, the pooled HR was 1.39 (95%CI 0.97 to 1.98 by univariate analysis and 1.42 (95%CI 0.56 to 3.60 by multivariate analysis.The results indicated that no statistically significant association was found between mTOR/p-mTOR expression and NSCLC patients' prognosis.

Role of mTOR Inhibitors in Kidney Disease

Directory of Open Access Journals (Sweden)

Moto Kajiwara

2016-06-01

Full Text Available The first compound that inhibited the mammalian target of rapamycin (mTOR, sirolimus (rapamycin was discovered in the 1970s as a soil bacterium metabolite collected on Easter Island (Rapa Nui. Because sirolimus showed antiproliferative activity, researchers investigated its molecular target and identified the TOR1 and TOR2. The mTOR consists of mTOR complex 1 (mTORC1 and mTORC2. Rapalogues including sirolimus, everolimus, and temsirolimus exert their effect mainly on mTORC1, whereas their inhibitory effect on mTORC2 is mild. To obtain compounds with more potent antiproliferative effects, ATP-competitive inhibitors of mTOR targeting both mTORC1 and mTORC2 have been developed and tested in clinical trials as anticancer drugs. Currently, mTOR inhibitors are used as anticancer drugs against several solid tumors, and immunosuppressive agents for transplantation of various organs. This review discusses the role of mTOR inhibitors in renal disease with a particular focus on renal cancer, diabetic nephropathy, and kidney transplantation.

Evolutionarily conserved regulation of TOR signalling.

Science.gov (United States)

Takahara, Terunao; Maeda, Tatsuya

2013-07-01

The target of rapamycin (TOR) is an evolutionarily conserved protein kinase that regulates cell growth in response to various environmental as well as intracellular cues through the formation of 2 distinct TOR complexes (TORC), TORC1 and TORC2. Dysregulation of TORC1 and TORC2 activity is closely associated with various diseases, including diabetes, cancer and neurodegenerative disorders. Over the past few years, new regulatory mechanisms of TORC1 and TORC2 activity have been elucidated. Furthermore, recent advances in the study of TOR inhibitors have revealed previously unrecognized cellular functions of TORC1. In this review, we briefly summarize the current understanding of the evolutionarily conserved TOR signalling from upstream regulators to downstream events.

Mechanical stimulation induces mTOR signaling via an ERK-independent mechanism: implications for a direct activation of mTOR by phosphatidic acid.

Directory of Open Access Journals (Sweden)

Jae Sung You

Full Text Available Signaling by mTOR is a well-recognized component of the pathway through which mechanical signals regulate protein synthesis and muscle mass. However, the mechanisms involved in the mechanical regulation of mTOR signaling have not been defined. Nevertheless, recent studies suggest that a mechanically-induced increase in phosphatidic acid (PA may be involved. There is also evidence which suggests that mechanical stimuli, and PA, utilize ERK to induce mTOR signaling. Hence, we reasoned that a mechanically-induced increase in PA might promote mTOR signaling via an ERK-dependent mechanism. To test this, we subjected mouse skeletal muscles to mechanical stimulation in the presence or absence of a MEK/ERK inhibitor, and then measured several commonly used markers of mTOR signaling. Transgenic mice expressing a rapamycin-resistant mutant of mTOR were also used to confirm the validity of these markers. The results demonstrated that mechanically-induced increases in p70(s6k T389 and 4E-BP1 S64 phosphorylation, and unexpectedly, a loss in total 4E-BP1, were fully mTOR-dependent signaling events. Furthermore, we determined that mechanical stimulation induced these mTOR-dependent events, and protein synthesis, through an ERK-independent mechanism. Similar to mechanical stimulation, exogenous PA also induced mTOR-dependent signaling via an ERK-independent mechanism. Moreover, PA was able to directly activate mTOR signaling in vitro. Combined, these results demonstrate that mechanical stimulation induces mTOR signaling, and protein synthesis, via an ERK-independent mechanism that potentially involves a direct interaction of PA with mTOR. Furthermore, it appears that a decrease in total 4E-BP1 may be part of the mTOR-dependent mechanism through which mechanical stimuli activate protein synthesis.

Internalization of Malaysian mathematical and computer science journals

OpenAIRE

Zainab, A. N.

2008-01-01

The internationalization characteristics of two Malaysian journals, Bulletin of the Malaysian Mathematical Sciences Society ( indexed by ISI) and the Malaysian Journal of Computer Science ( indexed by Inspec and Scopus) is observed. All issues for the years 2000 to 2007 were looked at to obtain the following information, (i) total articles published between 2000 and 2007; (ii) the distribution of foreign and Malaysian authors publishing in the journals; (iii) the distribution of articles by c...

Enhancing Malaysian Teachers' Assessment Literacy

Science.gov (United States)

Lian, Lim Hooi; Yew, Wun Thiam; Meng, Chew Cheng

2014-01-01

Currently, in order to reform the Malaysian education system, there have been a number of education policy initiatives launched by the Malaysian Ministry of Education (MOE). All these initiatives have encouraged and inculcated teaching and learning for creativity, critical, innovative and higher-order thinking skills rather than conceptual…

Nutrient sensing and TOR signaling in yeast and mammals.

Science.gov (United States)

González, Asier; Hall, Michael N

2017-02-15

Coordinating cell growth with nutrient availability is critical for cell survival. The evolutionarily conserved TOR (target of rapamycin) controls cell growth in response to nutrients, in particular amino acids. As a central controller of cell growth, mTOR (mammalian TOR) is implicated in several disorders, including cancer, obesity, and diabetes. Here, we review how nutrient availability is sensed and transduced to TOR in budding yeast and mammals. A better understanding of how nutrient availability is transduced to TOR may allow novel strategies in the treatment for mTOR-related diseases. © 2017 The Authors.

Torness - why it should be stopped

Energy Technology Data Exchange (ETDEWEB)

1980-12-01

The subject is discussed under the following headings: South of Scotland Electricity Board's plans; Torness (proposed nuclear power plant) and Craigroyston (proposed pumped storage scheme); no need for it; overcapacity; premature closures (of other SSEB plants); unemployment; not 'local' (reference to workers at Torness); safety unknown; secrecy; halt called for (on safety grounds); mad economics; increasing construction costs; nuclear is not cheaper; a robust economic case (query); AGR problems; Hinkley point incident; Hunterston incident; refuelling; Torness AGR.

Selfrando: Securing the Tor Browser against De-anonymization Exploits

Directory of Open Access Journals (Sweden)

Conti Mauro

2016-10-01

Full Text Available Tor is a well-known anonymous communication system used by millions of users, including journalists and civil rights activists all over the world. The Tor Browser gives non-technical users an easy way to access the Tor Network. However, many government organizations are actively trying to compromise Tor not only in regions with repressive regimes but also in the free world, as the recent FBI incidents clearly demonstrate. Exploiting software vulnerabilities in general, and browser vulnerabilities in particular, constitutes a clear and present threat to the Tor software. The Tor Browser shares a large part of its attack surface with the Firefox browser. Therefore, Firefox vulnerabilities (even patched ones are highly valuable to attackers trying to monitor users of the Tor Browser.

Rhythmic patterning in Malaysian and Singapore English.

Science.gov (United States)

Tan, Rachel Siew Kuang; Low, Ee-Ling

2014-06-01

Previous work on the rhythm of Malaysian English has been based on impressionistic observations. This paper utilizes acoustic analysis to measure the rhythmic patterns of Malaysian English. Recordings of the read speech and spontaneous speech of 10 Malaysian English speakers were analyzed and compared with recordings of an equivalent sample of Singaporean English speakers. Analysis was done using two rhythmic indexes, the PVI and VarcoV. It was found that although the rhythm of read speech of the Singaporean speakers was syllable-based as described by previous studies, the rhythm of the Malaysian speakers was even more syllable-based. Analysis of the syllables in specific utterances showed that Malaysian speakers did not reduce vowels as much as Singaporean speakers in cases of syllables in utterances. Results of the spontaneous speech confirmed the findings for the read speech; that is, the same rhythmic patterning was found which normally triggers vowel reductions.

Advanced Research of mTOR and Lung Carcinoid Tumors

Directory of Open Access Journals (Sweden)

Zixuan ZHANG

2013-01-01

Full Text Available Mammalian target of rapamycin (mTOR, a main protein kinase in the phosphoinositide 3-kinase (PI3K/AKT/mTOR signaling pathway, is an important intracellular mediator involved in multiple celluar functions including proliferation, differentiation, apoptosis, tumorigenesis, and angiogenesis. Recently, the high expression of mTOR and mTOR-related kinase have been found in neuroendocrin tumors. Therefore, mTOR pathway represents an attractive target for new anticancer therapies except surgery.

Glacial modification of granite tors in the Cairngorms, Scotland

Science.gov (United States)

Hall, A.M.; Phillips, W.M.

2006-01-01

A range of evidence indicates that many granite tors in the Cairngorms have been modified by the flow of glacier ice during the Pleistocene. Comparisons with SW England and the use of a space-time transformation across 38 tor groups in the Cairngorms allow a model to be developed for progressive glacial modification. Tors with deeply etched surfaces and no, or limited, block removal imply an absence of significant glacial modification. The removal of superstructure and blocks, locally forming boulder trains, and the progressive reduction of tors to stumps and basal slabs represent the more advanced stages of modification. Recognition of some slabs as tor stumps from which glacial erosion has removed all superstructure allows the original distribution of tors to be reconstructed for large areas of the Cairngorms. Unmodified tors require covers of non-erosive, cold-based ice during all of the cold stages of the Middle and Late Pleistocene. Deformation beneath cold-based glacier ice is capable of the removal of blocks but advanced glacial modification requires former wet-based glacier ice. The depth of glacial erosion at former tor sites remains limited largely to the partial or total elimination of the upstanding tor form. Cosmogenic nuclide exposure ages (Phillips et al., 2006) together with data from weathering pit depths (Hall and Phillips, 2006), from the surfaces of tors and large erratic blocks require that the glacial entrainment of blocks from tors occurred in Marine Isotope Stages (MIS) 4-2, 6 and, probably, at least one earlier phase. The occurrence of glacially modified tors on or close to, the main summits of the Cairngorms requires full ice cover over the mountains during these Stages. Evidence from the Cairngorms indicates that tor morphology can be regarded as an important indicator of former ice cover in many formerly glaciated areas, particularly where other evidence of ice cover is sparse. Recognition of the glacial modification of tors is important

Malaysian NDT standards

International Nuclear Information System (INIS)

Khazali Mohd Zin

2001-01-01

In order to become a developed country, Malaysia needs to develop her own national standards. It has been projected that by the year 2020, Malaysia requires about 8,000 standards (Department of Standard Malaysia). Currently more than 2,000 Malaysian Standards have been gazette by the government which considerably too low before tire year 2020. NDT standards have been identified by the standard working group as one of the areas to promote our national standards. In this paper the author describes the steps taken to establish the Malaysian very own NDT standards. The project starts with the establishment of radiographic standards. (Author)

TOR Signaling and Nutrient Sensing.

Science.gov (United States)

Dobrenel, Thomas; Caldana, Camila; Hanson, Johannes; Robaglia, Christophe; Vincentz, Michel; Veit, Bruce; Meyer, Christian

2016-04-29

All living organisms rely on nutrients to sustain cell metabolism and energy production, which in turn need to be adjusted based on available resources. The evolutionarily conserved target of rapamycin (TOR) protein kinase is a central regulatory hub that connects environmental information about the quantity and quality of nutrients to developmental and metabolic processes in order to maintain cellular homeostasis. TOR is activated by both nitrogen and carbon metabolites and promotes energy-consuming processes such as cell division, mRNA translation, and anabolism in times of abundance while repressing nutrient remobilization through autophagy. In animals and yeasts, TOR acts antagonistically to the starvation-induced AMP-activated kinase (AMPK)/sucrose nonfermenting 1 (Snf1) kinase, called Snf1-related kinase 1 (SnRK1) in plants. This review summarizes the immense knowledge on the relationship between TOR signaling and nutrients in nonphotosynthetic organisms and presents recent findings in plants that illuminate the crucial role of this pathway in conveying nutrient-derived signals and regulating many aspects of metabolism and growth.

The reprocessing of fast reactor fuels - the TOR project

International Nuclear Information System (INIS)

Calame-Longjean, A.; Le Bouhellec, J.; Schwob, Y.

1982-01-01

A description is given of development work on the proposed new French facility for the reprocessing of fast reactor fuel. This is the TOR facility (Traitement des Oxydes Rapides). Block diagrams give details of the TOR project as a whole and of the main line and R and D line of the TOR 1 facility which is a new works devoted to the head of the process. Modifications to existing plant which will form the TOR 2 and TOR 3 facilities are also described. (U.K.)

TOR-Dependent and -Independent Pathways Regulate Autophagy in Arabidopsis thaliana.

Science.gov (United States)

Pu, Yunting; Luo, Xinjuan; Bassham, Diane C

2017-01-01

Autophagy is a critical process for recycling of cytoplasmic materials during environmental stress, senescence and cellular remodeling. It is upregulated under a wide range of abiotic stress conditions and is important for stress tolerance. Autophagy is repressed by the protein kinase target of rapamycin (TOR), which is activated in response to nutrients and in turn upregulates cell growth and translation and inhibits autophagy. Down-regulation of TOR in Arabidopsis thaliana leads to constitutive autophagy and to decreased growth, but the relationship to stress conditions is unclear. Here, we assess the extent to which TOR controls autophagy activation by abiotic stress. Overexpression of TOR inhibited autophagy activation by nutrient starvation, salt and osmotic stress, indicating that activation of autophagy under these conditions requires down-regulation of TOR activity. In contrast, TOR overexpression had no effect on autophagy induced by oxidative stress or ER stress, suggesting that activation of autophagy by these conditions is independent of TOR function. The plant hormone auxin has been shown previously to up-regulate TOR activity. To confirm the existence of two pathways for activation of autophagy, dependent on the stress conditions, auxin was added exogenously to activate TOR, and the effect on autophagy under different conditions was assessed. Consistent with the effect of TOR overexpression, the addition of the auxin NAA inhibited autophagy during nutrient deficiency, salt and osmotic stress, but not during oxidative or ER stress. NAA treatment was unable to block autophagy induced by a TOR inhibitor or by a mutation in the TOR complex component RAPTOR1B , indicating that auxin is upstream of TOR in the regulation of autophagy. We conclude that repression of auxin-regulated TOR activity is required for autophagy activation in response to a subset of abiotic stress conditions.

Lysophosphatidic acid acyltransferase beta regulates mTOR signaling.

Directory of Open Access Journals (Sweden)

Michelle A Blaskovich

Full Text Available Lysophosphatidic acid acyltransferase (LPAAT-β is a phosphatidic acid (PA generating enzyme that plays an essential role in triglyceride synthesis. However, LPAAT-β is now being studied as an important regulator of cell growth and differentiation and as a potential therapeutic target in cancer since PA is necessary for the activity of key proteins such as Raf, PKC-ζ and mTOR. In this report we determine the effect of LPAAT-β silencing with siRNA in pancreatic adenocarcinoma cell lines. We show for the first time that LPAAT-β knockdown inhibits proliferation and anchorage-independent growth of pancreatic cancer cells. This is associated with inhibition of signaling by mTOR as determined by levels of mTORC1- and mTORC2-specific phosphorylation sites on 4E-BP1, S6K and Akt. Since PA regulates the activity of mTOR by modulating its binding to FKBP38, we explored the possibility that LPAAT-β might regulate mTOR by affecting its association with FKBP38. Coimmunoprecipitation studies of FKBP38 with mTOR show increased levels of FKBP38 associated with mTOR when LPAAT-β protein levels are knocked down. Furthermore, depletion of LPAAT-β results in increased Lipin 1 nuclear localization which is associated with increased nuclear eccentricity, a nuclear shape change that is dependent on mTOR, further confirming the ability of LPAAT-β to regulate mTOR function. Our results provide support for the hypothesis that PA generated by LPAAT-β regulates mTOR signaling. We discuss the implications of these findings for using LPAAT-β as a therapeutic target.

The Challenges of Malaysian Dry Ports Development

Directory of Open Access Journals (Sweden)

Jagan Jeevan

2015-03-01

Full Text Available This paper examines the functions and challenges of dry ports development in Malaysia through 11 face-to-face interviews with dry port stakeholders. The findings reveal that Malaysian dry ports are developed to accelerate national and international business, to activate intermodalism in the nation, to promote regional economic development and to enhance seaport competitiveness. Malaysian dry ports perform the function of transport and logistics, information processing, seaports and value-added services. Challenges facing Malaysian dry ports include insufficient railway tracks, unorganized container planning on the rail deck, highly dependent on single mode of transportation, poor recognition from the seaport community, and competition from localized seaports. This paper further indicates strategies for coping with these challenges and identifies future opportunities for Malaysian dry ports development.

Sulfur availability regulates plant growth via glucose-TOR signaling.

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Dong, Yihan; Silbermann, Marleen; Speiser, Anna; Forieri, Ilaria; Linster, Eric; Poschet, Gernot; Allboje Samami, Arman; Wanatabe, Mutsumi; Sticht, Carsten; Teleman, Aurelio A; Deragon, Jean-Marc; Saito, Kazuki; Hell, Rüdiger; Wirtz, Markus

2017-10-27

Growth of eukaryotic cells is regulated by the target of rapamycin (TOR). The strongest activator of TOR in metazoa is amino acid availability. The established transducers of amino acid sensing to TOR in metazoa are absent in plants. Hence, a fundamental question is how amino acid sensing is achieved in photo-autotrophic organisms. Here we demonstrate that the plant Arabidopsis does not sense the sulfur-containing amino acid cysteine itself, but its biosynthetic precursors. We identify the kinase GCN2 as a sensor of the carbon/nitrogen precursor availability, whereas limitation of the sulfur precursor is transduced to TOR by downregulation of glucose metabolism. The downregulated TOR activity caused decreased translation, lowered meristematic activity, and elevated autophagy. Our results uncover a plant-specific adaptation of TOR function. In concert with GCN2, TOR allows photo-autotrophic eukaryotes to coordinate the fluxes of carbon, nitrogen, and sulfur for efficient cysteine biosynthesis under varying external nutrient supply.

Data-plane Defenses against Routing Attacks on Tor

Directory of Open Access Journals (Sweden)

Tan Henry

2016-10-01

Full Text Available Tor is susceptible to traffic correlation attacks in which an adversary who observes flows entering and leaving the anonymity network can apply statistical techniques to correlate flows and de-anonymize their endpoints. While an adversary may not be naturally positioned to conduct such attacks, a recent study shows that the Internet’s control-plane can be manipulated to increase an adversary’s view of the network, and consequently, improve its ability to perform traffic correlation. This paper explores, in-depth, the effects of control-plane attacks on the security of the Tor network. Using accurate models of the live Tor network, we quantify Tor’s susceptibility to these attacks by measuring the fraction of the Tor network that is vulnerable and the advantage to the adversary of performing the attacks. We further propose defense mechanisms that protect Tor users from manipulations at the control-plane. Perhaps surprisingly, we show that by leveraging existing trust anchors in Tor, defenses deployed only in the data-plane are sufficient to detect most control-plane attacks. Our defenses do not assume the active participation of Internet Service Providers, and require only very small changes to Tor. We show that our defenses result in a more than tenfold decrease in the effectiveness of certain control-plane attacks.

Red de anonimización TOR y cibermercados negros

OpenAIRE

González Muñoz, Ignacio

2018-01-01

El trabajo se centra en el entorno de la red Tor. Se describe qué es Tor, sus componentes y el funcionamiento de la red. Se realiza un estudio de los métodos de desanonimización de usuarios, así como los ataques que puede sufrir la red. También se analizan los mercados ocultos que hay en Tor y las criptomonedas que se utilizan en estos mercados. El treball es centra en l'entorn de la xarxa Tor. Es descriu què és Tor, els seus components i el funcionament de la xarxa. Es realitza un estudi ...

The mTOR signalling pathway in cancer and the potential mTOR inhibitory activities of natural phytochemicals.

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Tan, Heng Kean; Moad, Ahmed Ismail Hassan; Tan, Mei Lan

2014-01-01

The mammalian target of rapamycin (mTOR) kinase plays an important role in regulating cell growth and cell cycle progression in response to cellular signals. It is a key regulator of cell proliferation and many upstream activators and downstream effectors of mTOR are known to be deregulated in various types of cancers. Since the mTOR signalling pathway is commonly activated in human cancers, many researchers are actively developing inhibitors that target key components in the pathway and some of these drugs are already on the market. Numerous preclinical investigations have also suggested that some herbs and natural phytochemicals, such as curcumin, resveratrol, timosaponin III, gallic acid, diosgenin, pomegranate, epigallocatechin gallate (EGCC), genistein and 3,3'-diindolylmethane inhibit the mTOR pathway either directly or indirectly. Some of these natural compounds are also in the clinical trial stage. In this review, the potential anti-cancer and chemopreventive activities and the current status of clinical trials of these phytochemicals are discussed.

Potyviruses differ in their requirement for TOR signalling.

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Ouibrahim, Laurence; Rubio, Ana Giner; Moretti, André; Montané, Marie-Hélène; Menand, Benoît; Meyer, Christian; Robaglia, Christophe; Caranta, Carole

2015-09-01

Potyviruses are important plant pathogens that rely on many plant cellular processes for successful infection. TOR (target of rapamycin) signalling is a key eukaryotic energy-signalling pathway controlling many cellular processes such as translation and autophagy. The dependence of potyviruses on active TOR signalling was examined. Arabidopsis lines downregulated for TOR by RNAi were challenged with the potyviruses watermelon mosaic virus (WMV) and turnip mosaic virus (TuMV). WMV accumulation was found to be severely altered while TuMV accumulation was only slightly delayed. In another approach, using AZD-8055, an active site inhibitor of the TOR kinase, WMV infection was found to be strongly affected. Moreover, AZD-8055 application can cure WMV infection. In contrast, TuMV infection was not affected by AZD-8055. This suggests that potyviruses have different cellular requirements for active plant TOR signalling.

Divergence of iron metabolism in wild Malaysian yeast.

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Lee, Hana N; Mostovoy, Yulia; Hsu, Tiffany Y; Chang, Amanda H; Brem, Rachel B

2013-12-09

Comparative genomic studies have reported widespread variation in levels of gene expression within and between species. Using these data to infer organism-level trait divergence has proven to be a key challenge in the field. We have used a wild Malaysian population of S. cerevisiae as a test bed in the search to predict and validate trait differences based on observations of regulatory variation. Malaysian yeast, when cultured in standard medium, activated regulatory programs that protect cells from the toxic effects of high iron. Malaysian yeast also showed a hyperactive regulatory response during culture in the presence of excess iron and had a unique growth defect in conditions of high iron. Molecular validation experiments pinpointed the iron metabolism factors AFT1, CCC1, and YAP5 as contributors to these molecular and cellular phenotypes; in genome-scale sequence analyses, a suite of iron toxicity response genes showed evidence for rapid protein evolution in Malaysian yeast. Our findings support a model in which iron metabolism has diverged in Malaysian yeast as a consequence of a change in selective pressure, with Malaysian alleles shifting the dynamic range of iron response to low-iron concentrations and weakening resistance to extreme iron toxicity. By dissecting the iron scarcity specialist behavior of Malaysian yeast, our work highlights the power of expression divergence as a signpost for biologically and evolutionarily relevant variation at the organismal level. Interpreting the phenotypic relevance of gene expression variation is one of the primary challenges of modern genomics.

Utility of the Canadian Treatment Optimization Recommendations (TOR) in MS care.

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Grand'Maison, François; Bhan, Virender; Freedman, Mark S; Myles, Mary L; Patry, David G; Selchen, Daniel H; Moriarty, Patrick; Traboulsee, Anthony L

2013-07-01

Criteria for Treatment Optimization Recommendations (TOR) for patients with multiple sclerosis (MS) identify suboptimal response to disease-modifying treatment (DMT). The Canadian TOR (CanTOR) were used to indicate recommendations for treatment switches or treatment maintenance based on relapse, disease progression and magnetic resonance imaging (MRI) criteria in patients. We assessed concordance between the TOR and clinicians' decisions regarding treatment response and identified prevalence of patients with MS receiving DMT meeting medium/high levels of concern according to TOR. Prospective baseline and end-of-study assessments of patients with relapsing-remitting MS (RRMS) or clinically isolated syndrome were conducted in this open-label, 12-month, Phase IV, observational Canadian study. Data were reported for 184 patients (female 72%, mean age 39 years) of which 96% had RRMS. The TOR criteria identified 19 (10.3%) patients with suboptimal response to treatment. Twelve patients had ≥1 high level of concern. Two patients had ≥2 medium levels of concern. Concordance between TOR and clinician decision in maintaining treatment was 95.3%. Where treatment change was recommended by the TOR, concordance was 29.4%. Clinicians identified the TOR as the principal reason for changing treatment in 50.0% of cases where the TOR identified suboptimal response. The TOR were considered useful by 70.6% of clinicians when treatment optimization was recommended and by 55.3% when maintaining treatment was recommended. The TOR criteria can identify suboptimal response in this patient cohort. Concordance between TOR and clinician decision was high when maintaining treatment was recommended. Usefulness of the TOR was most apparent when treatment optimization was recommended.

SPORTS WATCHING CULTURE AMONG MALAYSIANS

OpenAIRE

Gunathevan Elumalai; Mohd Salleh Aman; Cassendra Gilbert; Muhammad Mat Yusof; Ahmad Tajuddin Othman; Lim Khong Chiu; Mohd Sofian Omar Fauzee; Hamdan Mohd Ali

2015-01-01

Background: Ardent sports watching will lead an individual to engage in sports and recreational activities continuously, while it also creates a sports culture among Malaysians. Sports watching culture is actually an intellectual activity. It is capable of evaluating behaviour, moral values and the level of appreciation of every spectator. Methods: This survey was conducted to identify the sports viewing culture among Malaysians. A cluster sampling method was used to select 6000 respondent...

mTOR-Dependent Cell Proliferation in the Brain

Directory of Open Access Journals (Sweden)

Larisa Ryskalin

2017-01-01

Full Text Available The mammalian Target of Rapamycin (mTOR is a molecular complex equipped with kinase activity which controls cell viability being key in the PI3K/PTEN/Akt pathway. mTOR acts by integrating a number of environmental stimuli to regulate cell growth, proliferation, autophagy, and protein synthesis. These effects are based on the modulation of different metabolic pathways. Upregulation of mTOR associates with various pathological conditions, such as obesity, neurodegeneration, and brain tumors. This is the case of high-grade gliomas with a high propensity to proliferation and tissue invasion. Glioblastoma Multiforme (GBM is a WHO grade IV malignant, aggressive, and lethal glioma. To date, a few treatments are available although the outcome of GBM patients remains poor. Experimental and pathological findings suggest that mTOR upregulation plays a major role in determining an aggressive phenotype, thus determining relapse and chemoresistance. Among several activities, mTOR-induced autophagy suppression is key in GBM malignancy. In this article, we discuss recent evidence about mTOR signaling and its role in normal brain development and pathological conditions, with a special emphasis on its role in GBM.

mTOR-Dependent Cell Proliferation in the Brain.

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Ryskalin, Larisa; Lazzeri, Gloria; Flaibani, Marina; Biagioni, Francesca; Gambardella, Stefano; Frati, Alessandro; Fornai, Francesco

2017-01-01

The mammalian Target of Rapamycin (mTOR) is a molecular complex equipped with kinase activity which controls cell viability being key in the PI3K/PTEN/Akt pathway. mTOR acts by integrating a number of environmental stimuli to regulate cell growth, proliferation, autophagy, and protein synthesis. These effects are based on the modulation of different metabolic pathways. Upregulation of mTOR associates with various pathological conditions, such as obesity, neurodegeneration, and brain tumors. This is the case of high-grade gliomas with a high propensity to proliferation and tissue invasion. Glioblastoma Multiforme (GBM) is a WHO grade IV malignant, aggressive, and lethal glioma. To date, a few treatments are available although the outcome of GBM patients remains poor. Experimental and pathological findings suggest that mTOR upregulation plays a major role in determining an aggressive phenotype, thus determining relapse and chemoresistance. Among several activities, mTOR-induced autophagy suppression is key in GBM malignancy. In this article, we discuss recent evidence about mTOR signaling and its role in normal brain development and pathological conditions, with a special emphasis on its role in GBM.

FACTORS INFLUENCING YIELD SPREADS OF THE MALAYSIAN BONDS

OpenAIRE

Norliza Ahmad; Joriah Muhammad; Tajul Ariffin Masron

2009-01-01

Malaysian bond market is developing rapidly but not much is understood in terms of macroeconomic factors that could influence the yield spread of the Ringgit Malaysian denominated bonds. Based on a multifactor model, this paper examines the impact of four macroeconomic factors namely: Kuala Lumpur Composite Index (KLCI), Industry Production Index (IPI), Consumer Price Index (CPI) and interest rates (IR) on bond yield spread of the Malaysian Government Securities (MGS) and Corporate Bonds (CBs...

Overexpression of TOR (target of rapamycin) inhibits cell proliferation in Dictyostelium discoideum.

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Swer, Pynskhem Bok; Mishra, Himanshu; Lohia, Rakhee; Saran, Shweta

2016-05-01

TOR (target of rapamycin) protein kinase acts as a central controller of cell growth and development of an organism. Present study was undertaken to find the expression pattern and role of TOR during growth and development of Dictyostelium discoideum. Failures to generate either knockout and/or knockdown mutants indicate that interference with its levels led to cellular defects. Thus, the effects of TOR (DDB_G0281569) overexpression specifically, cells expressing Dd(Δ211-TOR)-Eyfp mutant was analyzed. Elevated expression of (Δ211-TOR)-Eyfp reduced both cell size and cell proliferation. DdTOR was found to be closer to fungus. mRNA level of TOR was found maximally in the freshly starved/aggregate cells that gradually declined. This was also strengthened by the expression patterns observed by in situ and the analysis of β-galactosidase reporter driven by the putative TOR promoter. The TOR protein was found to be highest at the aggregate stage. The fusion protein, (Δ211-TOR)-Eyfp was localized to the cell membrane, cytosol, and the nucleus. We suggest, DdTOR to be an essential protein and high TOR expression inhibits cell proliferation. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The nuclear import of ribosomal proteins is regulated by mTOR

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Kazyken, Dubek; Kaz, Yelimbek; Kiyan, Vladimir; Zhylkibayev, Assylbek A.; Chen, Chien-Hung; Agarwal, Nitin K.; Sarbassov, Dos D.

2014-01-01

Mechanistic target of rapamycin (mTOR) is a central component of the essential signaling pathway that regulates cell growth and proliferation by controlling anabolic processes in cells. mTOR exists in two distinct mTOR complexes known as mTORC1 and mTORC2 that reside mostly in cytoplasm. In our study, the biochemical characterization of mTOR led to discovery of its novel localization on nuclear envelope where it associates with a critical regulator of nuclear import Ran Binding Protein 2 (RanBP2). We show that association of mTOR with RanBP2 is dependent on the mTOR kinase activity that regulates the nuclear import of ribosomal proteins. The mTOR kinase inhibitors within thirty minutes caused a substantial decrease of ribosomal proteins in the nuclear but not cytoplasmic fraction. Detection of a nuclear accumulation of the GFP-tagged ribosomal protein rpL7a also indicated its dependence on the mTOR kinase activity. The nuclear abundance of ribosomal proteins was not affected by inhibition of mTOR Complex 1 (mTORC1) by rapamycin or deficiency of mTORC2, suggesting a distinctive role of the nuclear envelope mTOR complex in the nuclear import. Thus, we identified that mTOR in association with RanBP2 mediates the active nuclear import of ribosomal proteins. PMID:25294810

TOR signaling downregulation increases resistance to the cereal killer Fusarium graminearum.

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Aznar, Néstor R; Consolo, V Fabiana; Salerno, Graciela L; Martínez-Noël, Giselle M A

2018-02-01

TOR is the master regulator of growth and development that senses energy availability. Biotic stress perturbs metabolic and energy homeostasis, making TOR a good candidate to participate in the plant response. Fusarium graminearum (Fusarium) produces important losses in many crops all over the world. To date, the role of TOR in Fusarium infection has remained unexplored. Here, we show that the resistance to the pathogen increases in different Arabidopsis mutants impaired in TOR complex or in wild-type plants treated with a TOR inhibitor. We conclude that TOR signaling is involved in plant defense against Fusarium.

Resveratrol induces autophagy by directly inhibiting mTOR through ATP competition

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Park, Dohyun; Jeong, Heeyoon; Lee, Mi Nam; Koh, Ara; Kwon, Ohman; Yang, Yong Ryoul; Noh, Jungeun; Suh, Pann-Ghill; Park, Hwangseo; Ryu, Sung Ho

2016-01-01

Resveratrol (RSV) is a natural polyphenol that has a beneficial effect on health, and resveratrol-induced autophagy has been suggested to be a key process in mediating many beneficial effects of resveratrol, such as reduction of inflammation and induction of cancer cell death. Although various resveratrol targets have been suggested, the molecule that mediates resveratrol-induced autophagy remains unknown. Here, we demonstrate that resveratrol induces autophagy by directly inhibiting the mTOR-ULK1 pathway. We found that inhibition of mTOR activity and presence of ULK1 are required for autophagy induction by resveratrol. In line with this mTOR dependency, we found that resveratrol suppresses the viability of MCF7 cells but not of SW620 cells, which are mTOR inhibitor sensitive and insensitive cancer cells, respectively. We also found that resveratrol-induced cancer cell suppression occurred ULK1 dependently. For the mechanism of action of resveratrol on mTOR inhibition, we demonstrate that resveratrol directly inhibits mTOR. We found that resveratrol inhibits mTOR by docking onto the ATP-binding pocket of mTOR (i.e., it competes with ATP). We propose mTOR as a novel direct target of resveratrol, and inhibition of mTOR is necessary for autophagy induction. PMID:26902888

MH17: the Malaysian experience.

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Khoo, L S; Hasmi, A H; Abdul Ghani Aziz, S A; Ibrahim, M A; Mahmood, M S

2016-04-01

A disaster is a natural or man-made (or technological) hazard resulting in an event of substantial extent causing significant physical damage or destruction, loss of life, or drastic change to the environment. It is a phenomenon that can cause damage to life and property and destroy the economic, social and cultural life of the people; and overwhelms the capacity of the community to cope with the event. The recent tragic aviation accidents in 2014 involving Malaysia Airlines flights MH370 and MH17 shocked the world in an unprecedented manner. This paper focuses on the Malaysian experience in the MH17 mission in Ukraine as well as the first ever international Disaster Victim Identification (DVI) operation for the Malaysian DVI team. The DVI operations in Hilversum, the Netherlands were well described in stages. The Netherlands' Landelijk Team Forensische Opsporing as the lead DVI team in Hilversum operated systematically, ensuring the success of the whole mission. This paper discusses the lessons learned by the Malaysian team on proper DVI structure, inter- and intra-agency cooperation, facilities planning and set up, logistics and health and safety aspects, as well as effective communication and collaboration with other international delegates. Several issues and challenges faced by the Malaysian team were also documented. In addition, the authors shared views, opinions and recommendations for a more comprehensive DVI operation in the future.

Architecture of human mTOR complex 1.

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Aylett, Christopher H S; Sauer, Evelyn; Imseng, Stefan; Boehringer, Daniel; Hall, Michael N; Ban, Nenad; Maier, Timm

2016-01-01

Target of rapamycin (TOR), a conserved protein kinase and central controller of cell growth, functions in two structurally and functionally distinct complexes: TORC1 and TORC2. Dysregulation of mammalian TOR (mTOR) signaling is implicated in pathologies that include diabetes, cancer, and neurodegeneration. We resolved the architecture of human mTORC1 (mTOR with subunits Raptor and mLST8) bound to FK506 binding protein (FKBP)-rapamycin, by combining cryo-electron microscopy at 5.9 angstrom resolution with crystallographic studies of Chaetomium thermophilum Raptor at 4.3 angstrom resolution. The structure explains how FKBP-rapamycin and architectural elements of mTORC1 limit access to the recessed active site. Consistent with a role in substrate recognition and delivery, the conserved amino-terminal domain of Raptor is juxtaposed to the kinase active site. Copyright © 2016, American Association for the Advancement of Science.

mTOR as a Key Regulator in Maintaining Skeletal Muscle Mass

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Mee-Sup Yoon

2017-10-01

Full Text Available Maintenance of skeletal muscle mass is regulated by the balance between anabolic and catabolic processes. Mammalian target of rapamycin (mTOR is an evolutionarily conserved serine/threonine kinase, and is known to play vital roles in protein synthesis. Recent findings have continued to refine our understanding of the function of mTOR in maintaining skeletal muscle mass. mTOR controls the anabolic and catabolic signaling of skeletal muscle mass, resulting in the modulation of muscle hypertrophy and muscle wastage. This review will highlight the fundamental role of mTOR in skeletal muscle growth by summarizing the phenotype of skeletal-specific mTOR deficiency. In addition, the evidence that mTOR is a dual regulator of anabolism and catabolism in skeletal muscle mass will be discussed. A full understanding of mTOR signaling in the maintenance of skeletal muscle mass could help to develop mTOR-targeted therapeutics to prevent muscle wasting.

mTOR Signaling Confers Resistance to Targeted Cancer Drugs.

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Guri, Yakir; Hall, Michael N

2016-11-01

Cancer is a complex disease and a leading cause of death worldwide. Extensive research over decades has led to the development of therapies that target cancer-specific signaling pathways. However, the clinical benefits of such drugs are at best transient due to tumors displaying intrinsic or adaptive resistance. The underlying compensatory pathways that allow cancer cells to circumvent a drug blockade are poorly understood. We review here recent studies suggesting that mammalian TOR (mTOR) signaling is a major compensatory pathway conferring resistance to many cancer drugs. mTOR-mediated resistance can be cell-autonomous or non-cell-autonomous. These findings suggest that mTOR signaling should be monitored routinely in tumors and that an mTOR inhibitor should be considered as a co-therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

Rapamycin and Glucose-Target of Rapamycin (TOR) Protein Signaling in Plants*

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Xiong, Yan; Sheen, Jen

2012-01-01

Target of rapamycin (TOR) kinase is an evolutionarily conserved master regulator that integrates energy, nutrients, growth factors, and stress signals to promote survival and growth in all eukaryotes. The reported land plant resistance to rapamycin and the embryo lethality of the Arabidopsis tor mutants have hindered functional dissection of TOR signaling in plants. We developed sensitive cellular and seedling assays to monitor endogenous Arabidopsis TOR activity based on its conserved S6 kinase (S6K) phosphorylation. Surprisingly, rapamycin effectively inhibits Arabidopsis TOR-S6K1 signaling and retards glucose-mediated root and leaf growth, mimicking estradiol-inducible tor mutants. Rapamycin inhibition is relieved in transgenic plants deficient in Arabidopsis FK506-binding protein 12 (FKP12), whereas FKP12 overexpression dramatically enhances rapamycin sensitivity. The role of Arabidopsis FKP12 is highly specific as overexpression of seven closely related FKP proteins fails to increase rapamycin sensitivity. Rapamycin exerts TOR inhibition by inducing direct interaction between the TOR-FRB (FKP-rapamycin binding) domain and FKP12 in plant cells. We suggest that variable endogenous FKP12 protein levels may underlie the molecular explanation for longstanding enigmatic observations on inconsistent rapamycin resistance in plants and in various mammalian cell lines or diverse animal cell types. Integrative analyses with rapamycin and conditional tor and fkp12 mutants also reveal a central role of glucose-TOR signaling in root hair formation. Our studies demonstrate the power of chemical genetic approaches in the discovery of previously unknown and pivotal functions of glucose-TOR signaling in governing the growth of cotyledons, true leaves, petioles, and primary and secondary roots and root hairs. PMID:22134914

TOR signalling in plants.

Science.gov (United States)

Rexin, Daniel; Meyer, Christian; Robaglia, Christophe; Veit, Bruce

2015-08-15

Although the eukaryotic TOR (target of rapamycin) kinase signalling pathway has emerged as a key player for integrating nutrient-, energy- and stress-related cues with growth and metabolic outputs, relatively little is known of how this ancient regulatory mechanism has been adapted in higher plants. Drawing comparisons with the substantial knowledge base around TOR kinase signalling in fungal and animal systems, functional aspects of this pathway in plants are reviewed. Both conserved and divergent elements are discussed in relation to unique aspects associated with an autotrophic mode of nutrition and adaptive strategies for multicellular development exhibited by plants. © 2015 Authors; published by Portland Press Limited.

Growth in Malaysian Demand for Business Education--the Australian Response.

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Lewis, Philip E. T.; Pratt, Graham R.

1996-01-01

Increasing Malaysian demand for business education is examined from the perspective of Australia, one of the largest suppliers to the region. Topics discussed include: origins and nature of the demand; Malaysian enrollment patterns in Australia; "twinning programs," in which a Malaysian college and a foreign university collaborate to…

Main results from NILU`s participation in the TOR project; Hovedresultater fra NILUs deltakelse i TOR-prosjektet

Energy Technology Data Exchange (ETDEWEB)

Solberg, S; Stordahl, F

1996-01-01

The conference paper presents the main results from the Norwegian participation in the TOR (Tropospheric Ozone Research) project. The project was a part of the EUROTRAC environment programme which terminated in 1995. The aim of the TOR project was to increase the knowledge on physical and chemical processes being important for the consentration of ozone in the troposphere. 2 refs., 3 figs.

Managing Political Information: A Malaysian Perspective

Directory of Open Access Journals (Sweden)

Jamilah Ahmad

2010-07-01

Full Text Available In the development of democratization and the expression of civil and political rights of Malaysian citizens, the pattern of control developed by the regime that is currently in power (Barisan Nasional for the last 50 years in the mass media began to reap the resistance and tend to be ineffective. Malaysian citizens began to demand the Malaysian government to change the pattern of political information management. In addition, the mass media alone is expected to play a more significant role as an intermediary agent in supporting the process of transparency and accountability of government policy. This article shows that the openness of public information is a prerequisite for political democracy in Malaysia to help the government minimize the mis-management of governance policies, especially in finance and resource management.

mTOR inhibitors in urinary bladder cancer.

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Pinto-Leite, R; Arantes-Rodrigues, R; Sousa, Nuno; Oliveira, P A; Santos, L

2016-09-01

Despite the great scientific advances that have been made in cancer treatment, there is still much to do, particularly with regard to urinary bladder cancer. Some of the drugs used in urinary bladder cancer treatment have been in use for more than 30 years and show reduced effectiveness and high recurrence rates. There have been several attempts to find new and more effective drugs, to be used alone or in combination with the drugs already in use, in order to overcome this situation.The biologically important mammalian target of rapamycin (mTOR) pathway is altered in cancer and mTOR inhibitors have raised many expectations as potentially important anticancer drugs. In this article, the authors will review the mTOR pathway and present their experiences of the use of some mTOR inhibitors, sirolimus, everolimus and temsirolimus, in isolation and in conjunction with non-mTOR inhibitors cisplatin and gemcitabine, on urinary bladder tumour cell lines. The non-muscle-invasive cell line, 5637, is the only one that exhibits a small alteration in the mTOR and AKT phosphorylation after rapalogs exposure. Also, there was a small inhibition of cell proliferation. With gemcitabine plus everolimus or temsirolimus, the results were encouraging as a more effective response was noticed with both combinations, especially in the 5637 and T24 cell lines. Cisplatin associated with everolimus or temsirolimus also gave promising results, as an antiproliferative effect was observed when the drugs were associated, in particular on the 5637 and HT1376 cell lines. Everolimus or temsirolimus in conjunction with gemcitabine or cisplatin could have an important role to play in urinary bladder cancer treatment, depending on the tumour grading.

Anonymity communication VPN and Tor: a comparative study

Science.gov (United States)

Ramadhani, E.

2018-03-01

VPN and Tor is a technology based on anonymity communication. These two technologies have their advantage and disadvantage. The objective of this paper is to find the difference between VPN and Tor technologies by comparing their security of communication on the public network based on the CIA triad concept. The comparative study in this paper is based on the survey method. At last, the result of this paper is a recommendation on when to use a VPN and Tor to secure communication

Biotechnology issues in four Malaysian mainstream newspapers ...

African Journals Online (AJOL)

Biotechnology has been identified as the new engine of growth for the transformation of Malaysia into a developed nation by 2020. The objective of this paper is to analyze the impact of National Policy on biotechnology on media reporting in four Malaysian newspapers. Towards this end, a content analysis of four Malaysian ...

mTOR signaling and its roles in normal and abnormal brain development.

Directory of Open Access Journals (Sweden)

Nobuyuki eTakei

2014-04-01

Full Text Available Target of rapamycin (TOR was first identified in yeast as a target molecule of rapamycin, an anti-fugal and immunosuppressant macrolide compound. In mammals, its orthologue is called mTOR (mammalian TOR. mTOR is a serine/threonine kinase that converges different extracellular stimuli, such as nutrients and growth factors, and diverges into several biochemical reactions, including translation, autophagy, transcription, and lipid synthesis among others. These biochemical reactions govern cell growth and cause cells to attain an anabolic state. Thus, the disruption of mTOR signaling is implicated in a wide array of diseases such as cancer, diabetes, and obesity. In the central nervous system (CNS, the mTOR signaling cascade is activated by nutrients, neurotrophic factors, and neurotransmitters that enhances protein (and possibly lipid synthesis and suppresses autophagy. These processes contribute to normal neuronal growth by promoting their differentiation, neurite elongation and branching, and synaptic formation during development. Therefore, disruption of mTOR signaling may cause neuronal degeneration and abnormal neural development. While reduced mTOR signaling is associated with neurodegeneration, excess activation of mTOR signaling causes abnormal development of neurons and glia, leading to brain malformation. In this review, we first introduce the current state of molecular knowledge of mTOR complexes and signaling in general. We then describe mTOR activation in neurons, which leads to translational enhancement, and finally discuss the link between mTOR and normal/abnormal neuronal growth during development.

Historic day for Malaysian consumers.

Science.gov (United States)

Kaur, S R

1993-04-01

The Malaysian Medical Association, the Malaysian Dental Association, the Malaysian Pharmaceutical Society, and the Federation of Malaysian Consumer Associations have introduced and endorsed the Charter for Patient Rights. The Charter recognized that health care is a basic human right, regardless of race, religion, social status, and ability to pay. Further, consumers have the right to seek medical care in both the public and private sectors. The Charter also includes the right to a second opinion, one's own medical records, and explanation before receiving any medical treatment and concerning the risks of treatment, compensation for negligence, and adequate information. Malaysia is the second Asian country to have such a charter, South Korea being the first. The UK also has a Patients Charter. The rest of Europe is also moving to adopt such a charter. The private sector, which serves only those who can afford them, provides most health care services in developing countries. Thus, a large private sector threatens the elderly, unemployed, rural poor, and the mentally ill in these countries. The supply of these services is a marketable commodity which physicians and health care professionals own and sell. The medical community has planned, formulated, implemented, and monitored health services in most of these countries. Therefore, the private sector is a major obstacle to health for all. The Charter helps to break down the barrier by informing both physicians and their patients of their rights and responsibilities.

Assessing cultural intelligence of Malaysian expatriates in Netherlands

African Journals Online (AJOL)

Using purposive sampling method, a total of 320 questionnaires were distributed via email to Malaysian expatriates in Hague, Netherlands. Results from multiple regression analysis indicate that personality traits of agreeableness, openness and extraversion are significant to Malaysian expatriate's cultural intelligence.

Repositioning Strategy for Malaysian Companies Internationalization

Directory of Open Access Journals (Sweden)

Ismi Rajiani

2013-04-01

Full Text Available The rise of the emerging-market countries offers both developing and developed countries a unique opportunity to gain the benefits of a truly international economy. Consequently, it is imper- ative to advance our knowledge of emerging-market countries MNC emergence and competitive- ness including Malaysian firms on how will they position their products strategically. Based on the framework of Porter’s Generic Strategy, this paper is composed of price/ volume segments and im- pacts on product strategy theory. The aim is to identify crucial triggering cues and focus areas for Malaysian companies and measure what role these play in different segments. This study argues that some Malaysian companies will reposition themselves strategically when internationalizing and that they will focus on other factors or triggering cues when doing so not merely adapting the prevalent price leadership strategy.

Proof-of-Work as Anonymous Micropayment: Rewarding a Tor Relay

OpenAIRE

Biryukov, Alex; Pustogarov, Ivan

2015-01-01

In this paper we propose a new micropayments scheme which can be used to reward Tor relay operators. Tor clients do not pay Tor relays with electronic cash directly but submit proof of work shares which the relays can resubmit to a crypto-currency mining pool. Relays credit users who submit shares with tickets that can later be used to purchase improved service. Both shares and tickets when sent over Tor circuits are anonymous. The analysis of the crypto-currencies market prices shows that th...

Local learning processes in Malaysian industry

DEFF Research Database (Denmark)

Wangel, Arne

1999-01-01

Local learning processes are a vital part of any dynamic assimilation of transferred technology. The paper raises the question about the interaction between the training paradigms, which transnational corporations introduce in their subsidiaries in Malaysia and the specific basis for learning...... of Malaysian labour. Experiences from Malaysian industry indicate that local learning processes are shaped, among other things, by the concept of knowledge in a particular training programme, labour market structures, and learning cultures....

The emerging role of m-TOR up-regulation in brain Astrocytoma.

Science.gov (United States)

Ryskalin, Larisa; Limanaqi, Fiona; Biagioni, Francesca; Frati, Alessandro; Esposito, Vincenzo; Calierno, Maria Teresa; Lenzi, Paola; Fornai, Francesco

2017-05-01

The present manuscript is an overview of various effects of mTOR up-regulation in astrocytoma with an emphasis on its deleterious effects on the proliferation of Glioblastoma Multiforme. The manuscript reports consistent evidence indicating the occurrence of mTOR up-regulation both in experimental and human astrocytoma. The grading of human astrocytoma is discussed in relationship with mTOR up-regulation. In the second part of the manuscript, the biochemical pathways under the influence of mTOR are translated to cell phenotypes which are generated by mTOR up-regulation and reverted by its inhibition. A special section is dedicated to the prominent role of autophagy in mediating the effects of mTOR in glioblastoma. In detail, autophagy inhibition produced by mTOR up-regulation determines the fate of cancer stem cells. On the other hand, biochemical findings disclose the remarkable effects of autophagy activators as powerful inducers of cell differentiation with a strong prevalence towards neuronal phenotypes. Thus, mTOR modulation acts on the neurobiology of glioblastoma just like it operates in vivo at the level of brain stem cell niches by altering autophagy-dependent cell differentiation. In the light of such a critical role of autophagy we analyzed the ubiquitin proteasome system. The merging between autophagy and proteasome generates a novel organelle, named autophagoproteasome which is strongly induced by mTOR inhibitors in glioblastoma cells. Remarkably, when mTOR is maximally inhibited the proteasome component selectively moves within autophagy vacuoles, thus making the proteasome activity dependent on the entry within autophagy compartment.

Novel links in the plant TOR kinase signaling network.

Science.gov (United States)

Xiong, Yan; Sheen, Jen

2015-12-01

Nutrient and energy sensing and signaling mechanisms constitute the most ancient and fundamental regulatory networks to control growth and development in all life forms. The target of rapamycin (TOR) protein kinase is modulated by diverse nutrient, energy, hormone and stress inputs and plays a central role in regulating cell proliferation, growth, metabolism and stress responses from yeasts to plants and animals. Recent chemical, genetic, genomic and metabolomic analyses have enabled significant progress toward molecular understanding of the TOR signaling network in multicellular plants. This review discusses the applications of new chemical tools to probe plant TOR functions and highlights recent findings and predictions on TOR-mediate biological processes. Special focus is placed on novel and evolutionarily conserved TOR kinase effectors as positive and negative signaling regulators that control transcription, translation and metabolism to support cell proliferation, growth and maintenance from embryogenesis to senescence in the plant system. Copyright © 2015 Elsevier Ltd. All rights reserved.

[The effects of TorR protein on initiation of DNA replication in Escherichia coli].

Science.gov (United States)

Yuan, Yao; Jiaxin, Qiao; Jing, Li; Hui, Li; Morigen, Morigen

2015-03-01

The two-component systems, which could sense and respond to environmental changes, widely exist in bacteria as a signal transduction pathway. The bacterial CckA/CtrA, ArcA/ArcB and PhoP/PhoQ two-component systems are associated with initiation of DNA replication and cell division, however, the effects of the TorS/TorR system on cell cycle and DNA replication remains unknown. The TorS/TorR system in Escherichia coli can sense changes in trimethylamine oxide (TMAO) concentration around the cells. However, it is unknown if it also affects initiation of DNA replication. We detected DNA replication patterns in ΔtorS and ΔtorR mutant strains by flow cytometry. We found that the average number of replication origins (oriCs) per cell and doubling time in ΔtorS mutants were the same while the average number of oriCs in ΔtorR mutants was increased compared with that in wild-type cells. These results indicated that absence of TorR led to an earlier initiation of DNA replication than that in wild-type cells. Strangely, neither overexpression of TorR nor co-expression of TorR and TorS could restore ΔtorR mutant phenotype to the wild type. However, overexpression of SufD in both wild type and ΔtorR mutants promoted initiation of DNA replication, while mutation of SufD delayed it in ΔtorR mutants. Thus, TorR may affect initiation of DNA replication indirectly through regulating gene expression of sufD.

Three-dimensional facial analyses of Indian and Malaysian women.

Science.gov (United States)

Kusugal, Preethi; Ruttonji, Zarir; Gowda, Roopa; Rajpurohit, Ladusingh; Lad, Pritam; Ritu

2015-01-01

Facial measurements serve as a valuable tool in the treatment planning of maxillofacial rehabilitation, orthodontic treatment, and orthognathic surgeries. The esthetic guidelines of face are still based on neoclassical canons, which were used in the ancient art. These canons are considered to be highly subjective, and there is ample evidence in the literature, which raises such questions as whether or not these canons can be applied for the modern population. This study was carried out to analyze the facial features of Indian and Malaysian women by using three-dimensional (3D) scanner and thus determine the prevalence of neoclassical facial esthetic canons in both the groups. The study was carried out on 60 women in the age range of 18-25 years, out of whom 30 were Indian and 30 Malaysian. As many as 16 facial measurements were taken by using a noncontact 3D scanner. Unpaired t-test was used for comparison of facial measurements between Indian and Malaysian females. Two-tailed Fisher exact test was used to determine the prevalence of neoclassical canons. Orbital Canon was prevalent in 80% of Malaysian women; the same was found only in 16% of Indian women (P = 0.00013). About 43% of Malaysian women exhibited orbitonasal canon (P = 0.0470) whereas nasoaural canon was prevalent in 73% of Malaysian and 33% of Indian women (P = 0.0068). Orbital, orbitonasal, and nasoaural canon were more prevalent in Malaysian women. Facial profile canon, nasooral, and nasofacial canons were not seen in either group. Though some canons provide guidelines in esthetic analyses of face, complete reliance on these canons is not justifiable.

Idarubicin induces mTOR-dependent cytotoxic autophagy in leukemic cells

International Nuclear Information System (INIS)

Ristic, Biljana; Bosnjak, Mihajlo; Arsikin, Katarina; Mircic, Aleksandar; Suzin-Zivkovic, Violeta; Bogdanovic, Andrija; Perovic, Vladimir; Martinovic, Tamara; Kravic-Stevovic, Tamara; Bumbasirevic, Vladimir; Trajkovic, Vladimir; Harhaji-Trajkovic, Ljubica

2014-01-01

We investigated if the antileukemic drug idarubicin induces autophagy, a process of programmed cellular self-digestion, in leukemic cell lines and primary leukemic cells. Transmission electron microscopy and acridine orange staining demonstrated the presence of autophagic vesicles and intracellular acidification, respectively, in idarubicin-treated REH leukemic cell line. Idarubicin increased punctuation/aggregation of microtubule-associated light chain 3B (LC3B), enhanced the conversion of LC3B-I to autophagosome-associated LC3B-II in the presence of proteolysis inhibitors, and promoted the degradation of the selective autophagic target p62, thus indicating the increase in autophagic flux. Idarubicin inhibited the phosphorylation of the main autophagy repressor mammalian target of rapamycin (mTOR) and its downstream target p70S6 kinase. The treatment with the mTOR activator leucine prevented idarubicin-mediated autophagy induction. Idarubicin-induced mTOR repression was associated with the activation of the mTOR inhibitor AMP-activated protein kinase and down-regulation of the mTOR activator Akt. The suppression of autophagy by pharmacological inhibitors or LC3B and beclin-1 genetic knockdown rescued REH cells from idarubicin-mediated oxidative stress, mitochondrial depolarization, caspase activation and apoptotic DNA fragmentation. Idarubicin also caused mTOR inhibition and cytotoxic autophagy in K562 leukemic cell line and leukocytes from chronic myeloid leukemia patients, but not healthy controls. By demonstrating mTOR-dependent cytotoxic autophagy in idarubicin-treated leukemic cells, our results warrant caution when considering combining idarubicin with autophagy inhibitors in leukemia therapy. - Highlights: • Idarubicin induces autophagy in leukemic cell lines and primary leukemic cells. • Idarubicin induces autophagy by inhibiting mTOR in leukemic cells. • mTOR suppression by idarubicin is associated with AMPK activation and Akt blockade. �

Idarubicin induces mTOR-dependent cytotoxic autophagy in leukemic cells

Energy Technology Data Exchange (ETDEWEB)

Ristic, Biljana [Institute of Microbiology and Immunology, School of Medicine, University of Belgrade, Dr. Subotica 1, 11000 Belgrade (Serbia); Bosnjak, Mihajlo [Institute of Histology and Embryology, School of Medicine, University of Belgrade, Belgrade (Serbia); Arsikin, Katarina [Institute of Microbiology and Immunology, School of Medicine, University of Belgrade, Dr. Subotica 1, 11000 Belgrade (Serbia); Mircic, Aleksandar; Suzin-Zivkovic, Violeta [Institute of Histology and Embryology, School of Medicine, University of Belgrade, Belgrade (Serbia); Bogdanovic, Andrija [Clinic for Hematology, Clinical Centre of Serbia, School of Medicine, University of Belgrade, Belgrade (Serbia); Perovic, Vladimir [Institute of Microbiology and Immunology, School of Medicine, University of Belgrade, Dr. Subotica 1, 11000 Belgrade (Serbia); Martinovic, Tamara; Kravic-Stevovic, Tamara; Bumbasirevic, Vladimir [Institute of Histology and Embryology, School of Medicine, University of Belgrade, Belgrade (Serbia); Trajkovic, Vladimir, E-mail: vtrajkovic@med.bg.ac.rs [Institute of Microbiology and Immunology, School of Medicine, University of Belgrade, Dr. Subotica 1, 11000 Belgrade (Serbia); Harhaji-Trajkovic, Ljubica, E-mail: buajk@yahoo.com [Institute for Biological Research, University of Belgrade, Belgrade, Despot Stefan Blvd. 142, 11000 Belgrade (Serbia)

2014-08-01

We investigated if the antileukemic drug idarubicin induces autophagy, a process of programmed cellular self-digestion, in leukemic cell lines and primary leukemic cells. Transmission electron microscopy and acridine orange staining demonstrated the presence of autophagic vesicles and intracellular acidification, respectively, in idarubicin-treated REH leukemic cell line. Idarubicin increased punctuation/aggregation of microtubule-associated light chain 3B (LC3B), enhanced the conversion of LC3B-I to autophagosome-associated LC3B-II in the presence of proteolysis inhibitors, and promoted the degradation of the selective autophagic target p62, thus indicating the increase in autophagic flux. Idarubicin inhibited the phosphorylation of the main autophagy repressor mammalian target of rapamycin (mTOR) and its downstream target p70S6 kinase. The treatment with the mTOR activator leucine prevented idarubicin-mediated autophagy induction. Idarubicin-induced mTOR repression was associated with the activation of the mTOR inhibitor AMP-activated protein kinase and down-regulation of the mTOR activator Akt. The suppression of autophagy by pharmacological inhibitors or LC3B and beclin-1 genetic knockdown rescued REH cells from idarubicin-mediated oxidative stress, mitochondrial depolarization, caspase activation and apoptotic DNA fragmentation. Idarubicin also caused mTOR inhibition and cytotoxic autophagy in K562 leukemic cell line and leukocytes from chronic myeloid leukemia patients, but not healthy controls. By demonstrating mTOR-dependent cytotoxic autophagy in idarubicin-treated leukemic cells, our results warrant caution when considering combining idarubicin with autophagy inhibitors in leukemia therapy. - Highlights: • Idarubicin induces autophagy in leukemic cell lines and primary leukemic cells. • Idarubicin induces autophagy by inhibiting mTOR in leukemic cells. • mTOR suppression by idarubicin is associated with AMPK activation and Akt blockade. �

A Recollection of mTOR Signaling in Learning and Memory

Science.gov (United States)

Graber, Tyson E.; McCamphill, Patrick K.; Sossin, Wayne S.

2013-01-01

Mechanistic target of rapamcyin (mTOR) is a central player in cell growth throughout the organism. However, mTOR takes on an additional, more specialized role in the developed neuron, where it regulates the protein synthesis-dependent, plastic changes underlying learning and memory. mTOR is sequestered in two multiprotein complexes (mTORC1 and…

Emergency Management for Disasters in Malaysian Hotel Industry

Directory of Open Access Journals (Sweden)

AlBattat Ahmad Rasmi

2014-01-01

Full Text Available This paper aims to identify major emergencies that have the potential to place Malaysian hotels in emergency and disaster situations; investigate how hotels were prepared for emergencies, how they manage and overcome emergencies when occurred; and limitations and factors influencing successful emergency planning and adoption emergency management in Malaysian hotels. Face-to-face interview with managers from three, four and five star hotels from different backgrounds: local; regional; and International in Kuala Lumpur, Subang, and Putrajaya are undertaken. The result revealed that Malaysian hotels are exposed to a wide range of natural and man-made disasters. Malaysian hotels lack proactive emergency planning and a lot of constraints which impede successful emergency planning for disasters in the hotel industry in Malaysia, with emphasizing on the relevant authority’s role to demonstrate emergency management to hotels convincing them to adopt such practices, so they can be able to cope with emergencies effectively.

Malaysian and American Students' Perceptions of Research Ethics

Science.gov (United States)

Bowman, Laura L.; Anthonysamy, Angela

2006-01-01

Differences in perceptions of research ethics between Malaysian and American students were assessed using a questionnaire that measured perceptions of voluntary informed consent for adults and children, assessment of the risk/benefit ratio, issues of deception, and issues of privacy and confidentiality. As predicted, Malaysian students had less…

Language Learning Motivation among Malaysian Pre-University Students

Science.gov (United States)

Muftah, Muneera; Rafik-Galea, Shameem

2013-01-01

The study describes and examines Malaysian pre-university students' integrative and instrumental motivation toward learning English language. In this study, 182 non-English major students in one of the Malaysian public universities are selected to fill out a questionnaire reflecting their attitudes and motivation towards learning English. The…

The Development of a Green Practice Index for the Malaysian Hotel Industry

Directory of Open Access Journals (Sweden)

A. K. Siti–Nabiha

2014-03-01

Malaysian hotels. Doing so, however, resulted in a search for green index development methods. This lead to the discovery that existing tools such as the Delphi method were not appropriate tools that could be used to develop a Malaysian green index. To address the above, the authors propose a green index development method that can be used for a  Malaysian and developing country context. Hence, in this paper, the method of developing a green practice index for the Malaysian hospitality industry, the differences and advantages of this method compared to the commonly used Delphi method and finally the Malaysian Green Practice Index for the hotel industry are presented.

Formation process of Malaysian modern architecture under influence of nationalism

OpenAIRE

宇高, 雄志; 山崎, 大智

2001-01-01

This paper examines the Formation Process of Malaysian Modern Architecture under Influence of Nationalism,through the process of independence of Malaysia. The national style as "Malaysian national architecture" which hasengaged on background of political environment under the post colonial situation. Malaysian urban design is alsodetermined under the balance of both of ethnic culture and the national culture. In Malaysia, they decided to choosethe Malay ethnic culture as the national culture....

mTOR dysregulation and tuberous sclerosis-related epilepsy

NARCIS (Netherlands)

Curatolo, Paolo; Moavero, Romina; van Scheppingen, Jackelien; Aronica, Eleonora

2018-01-01

The mammalian target of rapamycin (mTOR) pathway has emerged as a key player for proper neural network development, and it is involved in epileptogenesis triggered by both genetic or acquired factors. Areas covered. The robust mTOR signaling deregulation observed in a large spectrum of epileptogenic

Activation of the TOR Signalling Pathway by Glutamine Regulates Insect Fecundity.

Science.gov (United States)

Zhai, Yifan; Sun, Zhongxiang; Zhang, Jianqing; Kang, Kui; Chen, Jie; Zhang, Wenqing

2015-05-29

The target of rapamycin (TOR) positively controls cell growth in response to nutrients such as amino acids. However, research on the specific nutrients sensed by TOR is limited. Glutamine (Gln), a particularly important amino acid involved in metabolism in organisms, is synthesised and catalysed exclusively by glutamine synthetase (GS), and our previous studies have shown that Gln may regulate fecundity in vivo levels of the brown planthopper (BPH) Nilaparvata lugens. Until now, it has remained unclear whether Gln activates or inhibits the TOR signalling pathway. Here, we performed the combined analyses of iTRAQ (isobaric tags for relative and absolute quantification) and DGE (tag-based digital gene expression) data in N. lugens at the protein and transcript levels after GS RNAi, and we found that 52 pathways overlap, including the TOR pathway. We further experimentally demonstrate that Gln activates the TOR pathway by promoting the serine/threonine protein kinase AKT and inhibiting the 5'AMP-activated protein kinase AMPK phosphorylation activity in the pest. Furthermore, TOR regulates the fecundity of N. lugens probably by mediating vitellogenin (Vg) expression. This work is the first report that Gln activates the TOR pathway in vivo.

The evolution of the TOR pathway and its role in cancer.

Science.gov (United States)

Beauchamp, E M; Platanias, L C

2013-08-22

The target of rapamycin (TOR) pathway is highly conserved among eukaryotes and has evolved to couple nutrient sensing to cellular growth. TOR is found in two distinct signaling complexes in cells, TOR complex 1 (TORC1) and TOR complex 2 (TORC2). These complexes are differentially regulated and act as effectors for the generation of signals that drive diverse cellular processes such as growth, proliferation, protein synthesis, rearrangement of the cytoskeleton, autophagy, metabolism and survival. Mammalian TOR (mTOR) is very important for development in embryos, while in adult organisms it is linked to aging and lifespan effects. In humans, the mTOR pathway is implicated in the tumorigenesis of multiple cancer types and its deregulation is associated with familial cancer syndromes. Because of its high biological relevance, different therapeutic strategies have been developed to target this signaling cascade, resulting in the emergence of unique pharmacological inhibitors that are either already approved for use in clinical oncology or currently under preclinical or clinical development. Multimodal treatment strategies that simultaneously target multiple nodes of the pathway and/or negative feedback regulatory loops may ultimately provide the best therapeutic advantage in targeting this pathway for the treatment of malignancies.

Attenuation of trace organic compounds (TOrCs) inbioelectrochemical systems

KAUST Repository

Werner, Craig M.

2015-04-01

Microbial fuel cells (MFCs) and microbial electrolysis cells (MECs) are two types of microbial bioelectrochemical systems (BESs) that use microorganisms to convert chemical energy in wastewaters into useful energy products such as (bio)electricity (MFC) or hydrogen gas (MEC). These two systems were evaluated for their capacity to attenuate trace organic compounds (TOrCs), commonly found in municipal wastewater, under closed circuit (current generation) and open circuit (no current generation) conditions, using acetate as the carbon source. A biocide was used to evaluate attenuation in terms of biotransformation versus sorption. The difference in attenuation observed before and after addition of the biocide represented biotransformation, while attenuation after addition of a biocide primarily indicated sorption. Attenuation of TOrCs was similar in MFCs and MECs for eight different TOrCs, except for caffeine and trimethoprim where slightly higher attenuation was observed in MECs. Electric current generation did not enhance attenuation of the TOrCs except for caffeine, which showed slightly higher attenuation under closed circuit conditions in both MFCs and MECs. Substantial sorption of the TOrCs occurred to the biofilm-covered electrodes, but no consistent trend could be identified regarding the physico-chemical properties of the TOrCs tested and the extent of sorption. The octanol-water distribution coefficient at pH 7.4 (log DpH 7.4) appeared to be a reasonable predictor for sorption of some of the compounds (carbamazepine, atrazine, tris(2-chloroethyl) phosphate and diphenhydramine) but not for others (N,N-Diethyl-meta-toluamide). Atenolol also showed high levels of sorption despite being the most hydrophilic in the suite of compounds studied (log DpH 7.4=-1.99). Though BESs do not show any inherent advantages over conventional wastewater treatment, with respect to TOrC removal, overall removals in BESs are similar to that reported for conventional wastewater

Self-Access Language Learning for Malaysian University Students

Science.gov (United States)

Tse, Andrew Yau Hau

2012-01-01

Just a few Malaysian universities offer self-access language learning activities to students. The objective of this study is to investigate if self-access learning can promote self-directed or autonomous learning in a public Malaysian technical university. Data collection is by means of interviewing the Director, lecturers, and students in a…

Lexical Borrowing from Chinese Languages in Malaysian English

Science.gov (United States)

Imm, Tan Siew

2009-01-01

This paper explores how contact between English and Chinese has resulted in the incorporation of Chinese borrowings into the lexicon of Malaysian English (ME). Using a corpus-based approach, this study analyses a comprehensive range of borrowed features extracted from the Malaysian English Newspaper Corpus (MEN Corpus). Based on the contexts of…

Malaysian English: An Instrumental Analysis of Vowel Contrasts

Science.gov (United States)

Pillai, Stefanie; Don, Zuraidah Mohd.; Knowles, Gerald; Tang, Jennifer

2010-01-01

This paper makes an instrumental analysis of English vowel monophthongs produced by 47 female Malaysian speakers. The focus is on the distribution of Malaysian English vowels in the vowel space, and the extent to which there is phonetic contrast between traditionally paired vowels. The results indicate that, like neighbouring varieties of English,…

Use of Tor (The Onion Router) disallowed from within CERN

CERN Multimedia

IT Department

2008-01-01

Tor is a freely available system enabling anonymous communication via the Internet between its users. Traffic is encrypted in multiple layers and flows through proxy servers . The use of Tor and similar anonymity systems may interfere with CERN’s security monitoring systems and increases the exposure of the CERN network to malicious or illegal material distributed via so-called "Tor Hidden Services". In addition, Tor has been used to mount attacks, including against CERN computers, and its installation could indicate a break-in. For the above reasons Tor and any similar systems will be added to the list of applications whose use is restricted at CERN and anyone who has used such an application is instructed to no longer do so. If a legitimate professional use can be justified then the Computer Security team should be informed and a prior security check made before installation of the software. CERN IT Department

Young Adult Literature in the Malaysian Secondary School

Science.gov (United States)

Govindarajoo, Mallika V.; Mukundan, Jayakaran

2013-01-01

This article presents the results of a study on the experience of the Malaysian secondary school student with Young Adult Literature in the English language classroom. The study aimed to determine the extent to which the Malaysian secondary school student identified with the young adult protagonists and issues in the novels which have been…

Plasticity and mTOR: Towards Restoration of Impaired Synaptic Plasticity in mTOR-Related Neurogenetic Disorders

Directory of Open Access Journals (Sweden)

Tanjala T. Gipson

2012-01-01

Full Text Available Objective. To review the recent literature on the clinical features, genetic mutations, neurobiology associated with dysregulation of mTOR (mammalian target of rapamycin, and clinical trials for tuberous sclerosis complex (TSC, neurofibromatosis-1 (NF1 and fragile X syndrome (FXS, and phosphatase and tensin homolog hamartoma syndromes (PTHS, which are neurogenetic disorders associated with abnormalities in synaptic plasticity and mTOR signaling. Methods. Pubmed and Clinicaltrials.gov were searched using specific search strategies. Results/Conclusions. Although traditionally thought of as irreversible disorders, significant scientific progress has been made in both humans and preclinical models to understand how pathologic features of these neurogenetic disorders can be reduced or reversed. This paper revealed significant similarities among the conditions. Not only do they share features of impaired synaptic plasticity and dysregulation of mTOR, but they also share clinical features—autism, intellectual disability, cutaneous lesions, and tumors. Although scientific advances towards discovery of effective treatment in some disorders have outpaced others, progress in understanding the signaling pathways that connect the entire group indicates that the lesser known disorders will become treatable as well.

Autophagy suppresses RIP kinase-dependent necrosis enabling survival to mTOR inhibition.

Directory of Open Access Journals (Sweden)

Kevin Bray

Full Text Available mTOR inhibitors are used clinically to treat renal cancer but are not curative. Here we show that autophagy is a resistance mechanism of human renal cell carcinoma (RCC cell lines to mTOR inhibitors. RCC cell lines have high basal autophagy that is required for survival to mTOR inhibition. In RCC4 cells, inhibition of mTOR with CCI-779 stimulates autophagy and eliminates RIP kinases (RIPKs and this is blocked by autophagy inhibition, which induces RIPK- and ROS-dependent necroptosis in vitro and suppresses xenograft growth. Autophagy of mitochondria is required for cell survival since mTOR inhibition turns off Nrf2 antioxidant defense. Thus, coordinate mTOR and autophagy inhibition leads to an imbalance between ROS production and defense, causing necroptosis that may enhance cancer treatment efficacy.

Tor forms a dimer through an N-terminal helical solenoid with a complex topology

Science.gov (United States)

Baretić, Domagoj; Berndt, Alex; Ohashi, Yohei; Johnson, Christopher M.; Williams, Roger L.

2016-04-01

The target of rapamycin (Tor) is a Ser/Thr protein kinase that regulates a range of anabolic and catabolic processes. Tor is present in two complexes, TORC1 and TORC2, in which the Tor-Lst8 heterodimer forms a common sub-complex. We have determined the cryo-electron microscopy (EM) structure of Tor bound to Lst8. Two Tor-Lst8 heterodimers assemble further into a dyad-symmetry dimer mediated by Tor-Tor interactions. The first 1,300 residues of Tor form a HEAT repeat-containing α-solenoid with four distinct segments: a highly curved 800-residue N-terminal 'spiral', followed by a 400-residue low-curvature 'bridge' and an extended `railing' running along the bridge leading to the 'cap' that links to FAT region. This complex topology was verified by domain insertions and offers a new interpretation of the mTORC1 structure. The spiral of one TOR interacts with the bridge of another, which together form a joint platform for the Regulatory Associated Protein of TOR (RAPTOR) regulatory subunit.

National space legislation : future perspectives for Malaysian Space Law

NARCIS (Netherlands)

Saari, Che Zuhaida Binti

2014-01-01

This research studies the future perspectives for Malaysian space law. It aims at demonstrating the development of Malaysian outer space activities inclusive of her status with respect to United Nations space conventions and her membership of international and regional space-related organizations.

Towards an Autonomous System Monitor for Mitigating Correlation Attacks in the Tor Network

OpenAIRE

Hoang, Nguyen Phong

2016-01-01

After carefully considering the scalability problem in Tor and exhaustively evaluating related works on AS-level adversaries, the author proposes ASmoniTor, which is an autonomous system monitor for mitigating correlation attacks in the Tor network. In contrast to prior works, which often released offline packets, including the source code of a modified Tor client and a snapshot of the Internet topology, ASmoniTor is an online system that assists end users with mitigating the threat of AS-lev...

The TOR Complex: An Emergency Switch for Root Behavior.

Science.gov (United States)

Yokawa, Ken; Baluška, František

2016-01-01

Target of rapamycin (TOR) kinase is known to be a controller of cell growth and aging, which determines the fine balance between growth rates and energy availabilities. It has been reported that many eukaryotes express TOR genes. In plants, TOR signaling modifies growth and development in response to a plant's energy status. An example of TOR action can be found in the root apices, which are active organs that explore the soil environment via vigorous growth and numerous tropisms. The exploratory nature of root apices requires a large energy supply for signaling, as well as for cell division and elongation. In the case of negative tropisms, roots must respond quickly to avoid patches of unfavorable soil conditions, again by consuming precious energy reserves. Here we review the current findings on TOR signaling in plants and animals, and propose possible roles for this important complex in driving plant root negative tropisms, particularly during light escape and salt avoidance behavior. © The Author 2015. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Gβγ interacts with mTOR and promotes its activation

Energy Technology Data Exchange (ETDEWEB)

Robles-Molina, Evelyn [Department of Pharmacology, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), Apartado postal 14-740, México, D.F. 07360 (Mexico); Dionisio-Vicuña, Misael [Department of Cell Biology, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), Apartado postal 14-740, México, D.F. 07360 (Mexico); Guzmán-Hernández, María Luisa [Department of Pharmacology, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), Apartado postal 14-740, México, D.F. 07360 (Mexico); Reyes-Cruz, Guadalupe [Department of Cell Biology, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), Apartado postal 14-740, México, D.F. 07360 (Mexico); Vázquez-Prado, José, E-mail: jvazquez@cinvestav.mx [Department of Pharmacology, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), Apartado postal 14-740, México, D.F. 07360 (Mexico)

2014-02-07

Highlights: • Gβγ interacts with mTOR kinase domain via a mechanism sensitive to chronic treatment with rapamycin. • Gβγ interacts with mTORC1 and mTORC2 which correlates with its ability to promote mTORC1 and mTORC2 signaling. • Gβγ heterodimers containing different Gβ subunits, except Gβ{sub 4}, interact with mTOR. - Abstract: Diverse G protein-coupled receptors depend on Gβγ heterodimers to promote cell polarization and survival via direct activation of PI3Kγ and potentially other effectors. These events involve full activation of AKT via its phosphorylation at Ser473, suggesting that mTORC2, the kinase that phosphorylates AKT at Ser473, is activated downstream of Gβγ. Thus, we tested the hypothesis that Gβγ directly contributes to mTOR signaling. Here, we demonstrate that endogenous mTOR interacts with Gβγ. Cell stimulation with serum modulates Gβγ interaction with mTOR. The carboxyl terminal region of mTOR, expressed as a GST-fusion protein, including the serine/threonine kinase domain, binds Gβγ heterodimers containing different Gβ subunits, except Gβ{sub 4}. Both, mTORC1 and mTORC2 complexes interact with Gβ{sub 1}γ{sub 2} which promotes phosphorylation of their respective substrates, p70S6K and AKT. In addition, chronic treatment with rapamycin, a condition known to interfere with assembly of mTORC2, reduces the interaction between Gβγ and mTOR and the phosphorylation of AKT; whereas overexpression of Gαi interfered with the effect of Gβγ as promoter of p70S6K and AKT phosphorylation. Altogether, our results suggest that Gβγ positively regulates mTOR signaling via direct interactions and provide further support to emerging strategies based on the therapeutical potential of inhibiting different Gβγ signaling interfaces.

mTOR Inhibition and Clinical Transplantation: Pancreas and Islet.

Science.gov (United States)

Berney, Thierry; Andres, Axel; Toso, Christian; Majno, Pietro; Squifflet, Jean-Paul

2018-02-01

This brief overview discusses the beneficial and deleterious effects of mammalian target of rapamycin (mTOR) inhibitors on β cells, and how sirolimus- and everolimus-based immunosuppression have impacted on practices and outcomes of pancreas and islet transplantation. Sirolimus was the cornerstone of immunosuppressive regimens in islet transplantation at the turn of the millenium, but utilization of mTOR inhibitors has progressively decreased from greater than 80% to less than 50% of islet transplant recipients in more recent years. For whole pancreas transplantation, mTOR inhibitors were used in approximately 20% of patients in the early 2000s, but this dropped over the years to less than 10% currently. This decrease is arguably due to less well-tolerated side effects without the advantage of better outcomes. Nonetheless, mTOR inhibitors remain extremely valuable as second-line immunosuppressants in pancreas and islet transplantation.

Fictionalized History: Signifying Changes to the Malaysian Nation and Identity

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Sim Chee Cheang

2016-04-01

Full Text Available As one of the cornerstones of fiction, writers often use and confront history in their claim to “reality” and “identity” in their writing. Linda Hutcheon’s claim for “a postmodern concern for the multiplicity and dispersion of truth(s; truth(s relative to the specificity of place and culture” (1988, p. 108 is relevant to the use of history in recent Malaysian literature. The multiple and varied claims of truth(s as reflected through the fictionalizing of Malaysian history is the focus of the analysis in this article, which aims to expose the social, economic, and political implications of the Malaysian identity. The analysis of three current works of fictionalized Malaysian history from the different fictional genres of comic series, children’s history, and occidental history, represents a cross section of genres that challenge the supremacy of history’s ontological claim over identity. The deliberate contestation of received Malaysian history in fictional modes acknowledges the peripheral identity structures of race, religion, and economics that are sensitive in a multiracial country such as Malaysia.

Distributed Performance Measurement and Usability Assessment of the Tor Anonymization Network

Directory of Open Access Journals (Sweden)

Steffen Kunz

2012-05-01

Full Text Available While the Internet increasingly permeates everyday life of individuals around the world, it becomes crucial to prevent unauthorized collection and abuse of personalized information. Internet anonymization software such as Tor is an important instrument to protect online privacy. However, due to the performance overhead caused by Tor, many Internet users refrain from using it. This causes a negative impact on the overall privacy provided by Tor, since it depends on the size of the user community and availability of shared resources. Detailed measurements about the performance of Tor are crucial for solving this issue. This paper presents comparative experiments on Tor latency and throughput for surfing to 500 popular websites from several locations around the world during the period of 28 days. Furthermore, we compare these measurements to critical latency thresholds gathered from web usability research, including our own user studies. Our results indicate that without massive future optimizations of Tor performance, it is unlikely that a larger part of Internet users would adopt it for everyday usage. This leads to fewer resources available to the Tor community than theoretically possible, and increases the exposure of privacy-concerned individuals. Furthermore, this could lead to an adoption barrier of similar privacy-enhancing technologies for a Future Internet.

Optimizing Managed Aquifer Recharge (MAR) Systems for Removal of Trace Organic Chemicals (TOrCs)

KAUST Repository

Alidina, Mazahirali

2014-06-01

Managed aquifer recharge (MAR) is a low-energy subsurface water treatment system with the potential of being an important component of sustainable water reuse schemes. Alongside common wastewater contaminants, MAR systems have been shown to attenuate a range of trace organic chemicals (TOrCs). Despite several factors being possibly important for TOrC attenuation, many have not been investigated in depth. This research effort investigated three factors affecting attenuation of the moderately degradable TOrCs: primary substrate, adaptation of the microbial community to presence of TOrCs, and groundwater temperature. The overall goal was to optimize TOrC attenuation using different MAR configurations considering how these factors affect TOrC attenuation. The primary substrate composition and concentration significantly impacted attenuation of the moderately degradable TOrCs. Lower primary substrate concentrations and more refractory carbon generally resulted in better TOrC transformation, a more diverse microbial community in the infiltration zone and more diverse capabilities for TOrC degradation. The enzyme group cytochrome P450 may be important for TOrC transformation since its genes were more abundant under carbon-starving primary substrate conditions. Adaptation of the microbial community by pre-exposure to TOrCs was not required in order to degrade them. However, adaptation to the primary substrate was necessary for TOrC biotransformation due to its effect on the microbial community. Attenuation of most TOrCs was unaffected by changes in temperature. Some moderately degradable TOrCs, however, were better attenuated at higher temperatures likely due to increased microbial activity. Others were better degraded at lower temperatures likely due to favorable sorption conditions. In the context of applying MAR systems to potential water reuse schemes within Saudi Arabia, a reconnaissance study of TOrC occurrence in treated wastewater effluents was undertaken. Most of

TOR-inhibitor insensitive-1 (TRIN1) regulates cotyledons greening in Arabidopsis.

Science.gov (United States)

Li, Linxuan; Song, Yun; Wang, Kai; Dong, Pan; Zhang, Xueyan; Li, Fuguang; Li, Zhengguo; Ren, Maozhi

2015-01-01

Target of Rapamycin (TOR) is an eukaryotic protein kinase and evolutionally conserved from the last eukaryotic common ancestor (LECA) to humans. The growing evidences have shown that TOR signaling acts as a central controller of cell growth and development. The downstream effectors of TOR have been well-identified in yeast and animals by using the immunosuppression agent rapamycin. However, less is known about TOR in plants. This is largely due to the fact that plants are insensitive to rapamycin. In this study, AZD8055 (AZD), the novel ATP-competitive inhibitor of TOR, was employed to decipher the downstream effectors of TOR in Arabidopsis. One AZD insensitive mutant, T O R - i nhibitor i n sensitive- 1 (trin1), was screened from 10,000 EMS-induced mutation seeds. The cotyledons of trin1 can turn green when its seeds were germinated on ½ MS medium supplemented with 2 μM AZD, whereas the cotyledons greening of wild-type (WT) can be completely blocked at this concentration. Through genetic mapping, TRIN1 was mapped onto the long arm of chromosome 2, between markers SGCSNP26 and MI277. Positional cloning revealed that TRIN1 was an allele of ABI4, which encoded an ABA-regulated AP2 domain transcription factor. Plants containing P35S::TRIN1 or P35S::TRIN1-GUS were hypersensitive to AZD treatment and displayed the opposite phenotype observed in trin1. Importantly, GUS signaling was significantly enhanced in P35S::TRIN1-GUS transgenic plants in response to AZD treatment, indicating that suppression of TOR resulted in the accumulation of TRIN1. These observations revealed that TOR controlled seed-to-seedling transition by negatively regulating the stability of TRIN1 in Arabidopsis. For the first time, TRIN1, the downstream effector of TOR signaling, was identified through a chemical genetics approach.

Waterfilling: Balancing the Tor network with maximum diversity

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Rochet Florentin

2017-04-01

Full Text Available We present the Waterfilling circuit selection method, which we designed in order to mitigate the risks of a successful end-to-end traffic correlation attack. Waterfilling proceeds by balancing the Tor network load as evenly as possible on endpoints of user paths. We simulate the use of Waterfilling thanks to the TorPS and Shadow tools. Applying several security metrics, we show that the adoption of Waterfilling considerably increases the number of nodes that an adversary needs to control in order to be able to mount a successful attack, while somewhat decreasing the minimum amount of bandwidth required to do so. Moreover, we evaluate Waterfilling in Shadow and show that it does not impact significantly the performance of the network. Furthermore, Waterfilling reduces the benefits that an attacker could obtain by hacking into a top bandwidth Tor relay, hence limiting the risks raised by such relays. Waterfilling does not require any major change in Tor, and can co-exist with the current circuit selection algorithm.

The Role of the Mammalian Target of Rapamycin (mTOR) in Pulmonary Fibrosis

Science.gov (United States)

Nho, Richard

2018-01-01

The phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR)-dependent pathway is one of the most integral pathways linked to cell metabolism, proliferation, differentiation, and survival. This pathway is dysregulated in a variety of diseases, including neoplasia, immune-mediated diseases, and fibroproliferative diseases such as pulmonary fibrosis. The mTOR kinase is frequently referred to as the master regulator of this pathway. Alterations in mTOR signaling are closely associated with dysregulation of autophagy, inflammation, and cell growth and survival, leading to the development of lung fibrosis. Inhibitors of mTOR have been widely studied in cancer therapy, as they may sensitize cancer cells to radiation therapy. Studies also suggest that mTOR inhibitors are promising modulators of fibroproliferative diseases such as idiopathic pulmonary fibrosis (IPF) and radiation-induced pulmonary fibrosis (RIPF). Therefore, mTOR represents an attractive and unique therapeutic target in pulmonary fibrosis. In this review, we discuss the pathological role of mTOR kinase in pulmonary fibrosis and examine how mTOR inhibitors may mitigate fibrotic progression. PMID:29518028

TOR, the Gateway to Cellular Metabolism, Cell Growth, and Disease.

Science.gov (United States)

Blenis, John

2017-09-21

Michael N. Hall is this year's recipient of the Lasker Basic Medical Research Award for the identification of the target of rapamycin, TOR. TOR is a master regulator of the cell's growth and metabolic state, and its dysregulation contributes to a variety of diseases, including diabetes, obesity, neurodegenerative disorders, aging, and cancer, making the TOR pathway an attractive therapeutic target. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

CHOLERA EL-TOR EN IRAN

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M. Ghodssi

1969-01-01

Full Text Available The bacteriological analysis shows that we have been confronted with the ELTor type, and only that type, until the end of the epidemic.The clinical study presents the symptoms of the real cholera with all its grievous consequences.The epidemiological supertnisicn stales that the El..Tor cholera is not agressiveat all in town areas whereas it presents its usual aspect in country areas, because of a lack of hygiene. there.That disease can be completely cured if the balance between the electrolytesis quickly restored.The disease was all the more dreadful since it came as a surprise and spread from one province to the other.L'examen bacteriologique montrc qu'il s'agit du type EI_ Tor et uniquement du meme type jusqu'a la fin de l'epldemie.La surveillance epidemiologique constate que Ie cholera EI_Tor n'cst nullement agressif dans Ie milieu urbain; mais qu'H revet l'aspect classique dans les milieuxruraux, depourvus d'hyglene.La maludic est totalement guerissablc a condition que l'equilibre des electrolytes so it rapidement retabli. L'evenement a tHe maladie se repandit d'une12

Factors Affecting Hypertension among the Malaysian Elderly

Science.gov (United States)

Eshkoor, Sima Ataollahi; Hamid, Tengku Aizan; Shahar, Suzana; Ng, Chee Kyun; Mun, Chan Yoke

2016-01-01

Hypertension is a common chronic disease in the elderly. This study aimed to determine the effects of age, ethnicity, gender, education, marital status, nutritional parameters, and blood elements on the risk of high blood pressure in the Malaysian elderly. This research was conducted on a group of 2322 non-institutionalized Malaysian elderly. The hierarchy binary logistic regression analysis was applied to estimate the risk of hypertension in respondents. Approximately, 45.61% of subjects had hypertension. The findings indicated that the female gender (Odds ratio (OR) = 1.54), an increase in body weight (OR = 1.61), and an increase in the blood levels of albumin (OR = 1.51), glucose (OR = 1.92), and triglycerides (OR = 1.27) significantly increased the risk of hypertension in subjects (p Malaysian elderly. In addition, an increase in both dietary carbohydrates and blood cholesterol level decreased hypertension in subjects. PMID:29367559

mTOR as a multifunctional therapeutic target in HIV infection

DEFF Research Database (Denmark)

Nicoletti, Ferdinando; Fagone, Paolo; Meroni, PierLuigi

2011-01-01

Patients undergoing long-term highly active antiretroviral therapy treatment are probably at a higher risk of various HIV-related complications. Hyperactivation of The mammalian target of rapamycin (mTOR) has been found to contribute to dysregulated apoptosis and autophagy which determine CD4(+)-T......-cell loss, impaired function of innate immunity and development of neurocognitive disorders. Dysregulated mTOR activation has also been shown to play a key part in the development of nephropathy and in the pathogenesis of HIV-associated malignancies. These studies strongly support a multifunctional key role...... for mTOR in the pathogenesis of HIV-related disorders and suggest that specific mTOR inhibitors could represent a novel approach for the prevention and treatment of these pathologies....

Analysis of mercury in Malaysian herbal preparations | Ang | Journal ...

African Journals Online (AJOL)

The rhizome of Smilax luzonensis is eaten as an aphrodisiac in the Malaysian community. This study was conducted to analyse the mercury content of 100 pharmaceutical dosage forms of S. luzonensis that were purchased in the Malaysian market, using cold vapour atomic absorption spectrophotometer. Results show that ...

Balancing act: matching growth with environment by the TOR signalling pathway.

Science.gov (United States)

Henriques, Rossana; Bögre, László; Horváth, Beátrix; Magyar, Zoltán

2014-06-01

One of the most fundamental aspects of growth in plants is its plasticity in relation to fluctuating environmental conditions. Growth of meristematic cells relies predominantly on protein synthesis, one of the most energy-consuming activities in cells, and thus is tightly regulated in accordance with the available nutrient and energy supplies. The Target of Rapamycin (TOR) signalling pathway takes a central position in this regulation. The core of the TOR signalling pathway is conserved throughout evolution, and can be traced back to the last eukaryotic common ancestor. In plants, a single complex constitutes the TOR signalling pathway. Manipulating the components of the TOR complex in Arabidopsis highlighted its common role as a major regulator of protein synthesis and metabolism, that is also involved in other biological functions such as cell-wall integrity, regulation of cell proliferation, and cell size. TOR, as an integral part of the auxin signalling pathway, connects hormonal and nutrient pathways. Downstream of TOR, S6 kinase and the ribosomal S6 protein have been shown to mediate several of these responses, although there is evidence of other complex non-linear TOR signalling pathway structures. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

The Significance of Malaysian Real Estate Research Agenda

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Muhammad Najib Razali

2011-12-01

Full Text Available This paper investigates research agenda by the Malaysian real estate researchers (MRERs. This study adopts a deskwork approach by examining research papers published in leading real estate journals, both international and local and papers presented in main real estate conferences from 1997 to 2010. In addition, the number of research papers published and presented were also assessed from several main real estate research journals in the US, UK, Asia/Australia and Malaysia and conferences such as American Real Estate Society (ARES, European Real Estate Society (ERES, Pacific Rim Real Estate Society (PRRES, Asian Real Estate Society (AsRES and local conference; International Real Estate Research Symposium (IRERS. The study indicates that the Malaysian real estate researchers (MRERs have made a positive contribution to the global real estate research. Nevertheless, there is still more effort needed in order to compete in the global real estate research agenda. It is anticipated that this trend will change since the Malaysian government has emphasised on improving the quality of higher learning institutions' for which research and publication will be the main agenda. The contribution from MRERs will significantly improve Malaysian universities standing in global ranking.

Shelf life assessment of Malaysian Pangasius sutchi during cold ...

Indian Academy of Sciences (India)

Malaysian Pangasius sutchi concerning the marketing sector from the point of view ... Patin (Pangasius sutchi) is a popular freshwater fish used as food in ... remaining shelf life allows a processor or a retailer to plan the length of time a product can be ... While consumption has increased, the Malaysian fisheries industry.

Property types diversification strategy of Malaysian real estate investment trust (M-REITs

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Ping Tiong Chai

2016-01-01

Full Text Available The aim of this paper is to review the property types diversification strategy of Malaysian REITs. Previous study has found that Malaysian REITs received poor response form investors both local and international. Furthermore, the underperformance of Malaysian REITs was linked to the characteristics of REITs’ property types and REITs’ portfolio influenced its financial performance. The lack of local study on both of these determinants of influence on performance of Malaysian REITs is a research gap, which needs to be explored that can provide more insight of it. This study showed that the property types such as office space, commercial lot, industrial, hotel and specialized property type are the important determinants, which can influence the performance of REITs. The study comprised of REITs data from 2010 until 2014, and through Multiple Regression Analysis (MRA reveals there is little influence of property types diversification strategy toward Malaysian REITs’ performance. Nevertheless, by employ correlation analysis between each of the five property types with expected return and dividend yield, this study shows Malaysian REITs’ performance of dividend yield(DY has a positive correlation value with commercial lot property type and Malaysian REITs’ performance of expected return(ER have a highest positive correlation value with industrial property types. Also, this study suggests that property type diversification play a significant role in Malaysia REITs. Other determinants such as location of property, market capitalization and REITs’ quality of advisory style that might influence the diversification strategy and financial performance of Malaysian REITs.

Relationship between oral hygiene and gingival condition of Malaysian students

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Muhammad Arif Mohd Marsin

2018-01-01

Full Text Available The primary etiologic agent of gingival disease was dental plaque which also involving the oral hygiene. The oral hygiene can be affected by individuals knowledge, attitude, practice, environment, and others. The purpose of this study was to assess the relationship between oral hygiene and gingival condition of Malaysian students. The type of this study was cross-sectional study. The study was conducted on a total of 66 Malaysian students. The data were collected by using an examination form and clinical examination using the Loe & Sillness gingival index followed by the Loe & Sillness plaque index. The results showed that 100% of students have gingivitis with the gingival index average of 1.25 and the plaque index average of 1.85. The relationship of gingival and plaque index was analyzed by using Spearman’s Rank Correlation Coefficient test, and the score was 0.623. It is concluded that the oral hygiene status of Malaysian students was in the fair category, and all Malaysian students had a moderate gingivitis. Also, there was a relationship between the oral hygiene status and gingival condition of Malaysian students.

TOR and paradigm change: cell growth is controlled.

Science.gov (United States)

Hall, Michael N

2016-09-15

This year marks the 25th anniversary of the discovery of target of rapamycin (TOR), a highly conserved kinase and central controller of cell growth. In this Retrospective, I briefly describe the discovery of TOR and the subsequent elucidation of its cellular role. I place particular emphasis on an article by Barbet et al. from 1996, the first suggesting that TOR controls cell growth in response to nutrients. © 2016 Hall. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

Rheb may complex with RASSF1A to coordinate Hippo and TOR signaling.

Science.gov (United States)

Nelson, Nicholas; Clark, Geoffrey J

2016-06-07

The TOR pathway is a vital component of cellular homeostasis that controls the synthesis of proteins, nucleic acids and lipids. Its core is the TOR kinase. Activation of the TOR pathway suppresses autophagy, which plays a vital but complex role in tumorigenesis. The TOR pathway is regulated by activation of the Ras-related protein Rheb, which can bind mTOR. The Hippo pathway is a major growth control module that regulates cell growth, differentiation and apoptosis. Its core consists of an MST/LATS kinase cascade that can be activated by the RASSF1A tumor suppressor. The TOR and Hippo pathways may be coordinately regulated to promote cellular homeostasis. However, the links between the pathways remain only partially understood. We now demonstrate that in addition to mTOR regulation, Rheb also impacts the Hippo pathway by forming a complex with RASSF1A. Using stable clones of two human lung tumor cell lines (NCI-H1792 and NCI-H1299) with shRNA-mediated silencing or ectopic overexpression of RASSF1A, we show that activated Rheb stimulates the Hippo pathway, but is suppressed in its ability to stimulate the TOR pathway. Moreover, by selectively labeling autophagic vacuoles we show that RASSF1A inhibits the ability of Rheb to suppress autophagy and enhance cell growth. Thus, we identify a new connection that impacts coordination of Hippo and TOR signaling. As RASSF1A expression is frequently lost in human tumors, the RASSF1A status of a tumor may impact not just its Hippo pathway status, but also its TOR pathway status.

Skeletal myocyte hypertrophy requires mTOR kinase activity and S6K1

International Nuclear Information System (INIS)

Park, In-Hyun; Erbay, Ebru; Nuzzi, Paul; Chen Jie

2005-01-01

The protein kinase mammalian target of rapamycin (mTOR) is a central regulator of cell proliferation and growth, with the ribosomal subunit S6 kinase 1 (S6K1) as one of the key downstream signaling effectors. A critical role of mTOR signaling in skeletal muscle differentiation has been identified recently, and an unusual regulatory mechanism independent of mTOR kinase activity and S6K1 is revealed. An mTOR pathway has also been reported to regulate skeletal muscle hypertrophy, but the regulatory mechanism is not completely understood. Here, we report the investigation of mTOR's function in insulin growth factor I (IGF-I)-induced C2C12 myotube hypertrophy. Added at a later stage when rapamycin no longer had any effect on normal myocyte differentiation, rapamycin completely blocked myocyte hypertrophy as measured by myotube diameter. Importantly, a concerted increase of average myonuclei per myotube was observed in IGF-I-stimulated myotubes, which was also inhibited by rapamycin added at a time when it no longer affected normal differentiation. The mTOR protein level, its catalytic activity, its phosphorylation on Ser2448, and the activity of S6K1 were all found increased in IGF-I-stimulated myotubes compared to unstimulated myotubes. Using C2C12 cells stably expressing rapamycin-resistant forms of mTOR and S6K1, we provide genetic evidence for the requirement of mTOR and its downstream effector S6K1 in the regulation of myotube hypertrophy. Our results suggest distinct mTOR signaling mechanisms in different stages of skeletal muscle development: While mTOR regulates the initial myoblast differentiation in a kinase-independent and S6K1-independent manner, the hypertrophic function of mTOR requires its kinase activity and employs S6K1 as a downstream effector

Issues and Problems in Malaysian Contemporary Visual Arts

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Mohamad Faizuan Mat

2016-06-01

Full Text Available In Malaysia, there is a question in term of intellectualism activities in the context of visual epistemology. Therefore, this paper revealed the problems that linger in the Malaysian contemporary visual art scene. In fact, Malaysian contemporary artists appear to have insufficient intellectualism values and less discourse activities. The lacks of scholars in the field of visual arts create a gap in the visual arts scene in Malaysia. The question of this study was to uncover the main problems in Malaysian visual arts that led to the problem of art intellectual development. In addition, this paper presents the awareness of the valuable contributions in the intellectual development that able to enhance the communication in the art object.Keywords: art knowledge; art object; contemporary art; interpretation; perception;

Malaysian Cinema, Asian Film

NARCIS (Netherlands)

Heide, van der William

2002-01-01

This title series departs from traditional studies of national cinema by accentuating the intercultural and intertextual links between Malaysian films and Asian (as well as European and American) film practices. Using cross-cultural analysis, the author characterizes Malaysia as a pluralist society

Evolutionary conservation of TORC1 components, TOR, Raptor, and LST8, between rice and yeast.

Science.gov (United States)

Maegawa, Kentaro; Takii, Rumi; Ushimaru, Takashi; Kozaki, Akiko

2015-10-01

Target of rapamycin (TOR) is a conserved eukaryotic serine/threonine kinase that functions as a central controller of cell growth. TOR protein is structurally defined by the presence several conserved domains such as the HEAT repeat, focal adhesion target (FAT), FKBP12/rapamycin binding (FRB), kinase, and FATC domains starting from the N-terminus. In most eukaryotes, TOR forms two distinct physical and functional complexes, which are termed as TOR complex 1 (TORC1) and TORC2. However, plants contain only TORC1 components, i.e., TOR, Raptor, and LST8. In this study, we analyzed the gene structure and functions of TORC components in rice to understand the properties of the TOR complex in plants. Comparison of the locations of introns in these genes among rice and other eukaryotes showed that they were well conserved among plants except for Chlamydomonas. Moreover, the intron positions in the coding sequence of human Raptor and LST8 were closer to those of plants than of fly or nematode. Complementation tests of rice TOR (OsTOR) components in yeast showed that although OsTOR did not complement yeast tor mutants, chimeric TOR, which consisted of the HEAT repeat and FAT domain from yeast and other regions from rice, rescued the tor mutants, indicating that the HEAT repeat and FAT domains are important for species-specific signaling. OsRaptor perfectly complemented a kog1 (yeast Raptor homolog) mutant, and OsLST8 partially complemented an lst8 mutant. Together, these data suggest the importance of the N-terminal region of the TOR, HEAT, and FAT domains for functional diversification of the TOR complex.

Are Malaysian Children Achieving Dietary Guideline Recommendations?

Science.gov (United States)

Koo, Hui Chin; Poh, Bee Koon; Lee, Shoo Thien; Chong, Kar Hau; Bragt, Marjolijn C E; Abd Talib, Ruzita

2016-07-01

A large body of epidemiological data has demonstrated that diet quality follows a sociodemographic gradient. Little is known, however, about food group intake patterns among Malaysian children. This study aimed to assess consumption pattern of 7 food groups, including cereals/grains, legumes, fruits, vegetables, fish, meat/poultry, and milk/dairy products, among children 7 to 12 years of age. A total of 1773 children who participated in SEANUTS Malaysia and who completed the Food Frequency Questionnaire were included in this study. A greater proportion of children aged 10 to 12 years have an inadequate intake of cereals/grains, meat/poultry, legumes, and milk/dairy products compared with children 7 to 9 years old. With the exception of meat/poultry, food consumption of Malaysian children did not meet Malaysian Dietary Guidelines recommendations for the other 6 food groups, irrespective of sociodemographic backgrounds. Efforts are needed to promote healthy and balanced dietary habits, particularly for foods that fall short of recommended intake level. © 2016 APJPH.

Inferring the effective TOR-dependent network: a computational study in yeast.

Science.gov (United States)

Mohammadi, Shahin; Subramaniam, Shankar; Grama, Ananth

2013-08-30

Calorie restriction (CR) is one of the most conserved non-genetic interventions that extends healthspan in evolutionarily distant species, ranging from yeast to mammals. The target of rapamycin (TOR) has been shown to play a key role in mediating healthspan extension in response to CR by integrating different signals that monitor nutrient-availability and orchestrating various components of cellular machinery in response. Both genetic and pharmacological interventions that inhibit the TOR pathway exhibit a similar phenotype, which is not further amplified by CR. In this paper, we present the first comprehensive, computationally derived map of TOR downstream effectors, with the objective of discovering key lifespan mediators, their crosstalk, and high-level organization. We adopt a systematic approach for tracing information flow from the TOR complex and use it to identify relevant signaling elements. By constructing a high-level functional map of TOR downstream effectors, we show that our approach is not only capable of recapturing previously known pathways, but also suggests potential targets for future studies.Information flow scores provide an aggregate ranking of relevance of proteins with respect to the TOR signaling pathway. These rankings must be normalized for degree bias, appropriately interpreted, and mapped to associated roles in pathways. We propose a novel statistical framework for integrating information flow scores, the set of differentially expressed genes in response to rapamycin treatment, and the transcriptional regulatory network. We use this framework to identify the most relevant transcription factors in mediating the observed transcriptional response, and to construct the effective response network of the TOR pathway. This network is hypothesized to mediate life-span extension in response to TOR inhibition. Our approach, unlike experimental methods, is not limited to specific aspects of cellular response. Rather, it predicts transcriptional

Target of Rapamycin (TOR) Regulates Growth in Response to Nutritional Signals.

Science.gov (United States)

Weisman, Ronit

2016-10-01

All organisms can respond to the availability of nutrients by regulating their metabolism, growth, and cell division. Central to the regulation of growth in response to nutrient availability is the target of rapamycin (TOR) signaling that is composed of two structurally distinct complexes: TOR complex 1 (TORC1) and TOR complex 2 (TORC2). The TOR genes were first identified in yeast as target of rapamycin, a natural product of a soil bacterium, which proved beneficial as an immunosuppressive and anticancer drug and is currently being tested for a handful of other pathological conditions including diabetes, neurodegeneration, and age-related diseases. Studies of the TOR pathway unraveled a complex growth-regulating network. TOR regulates nutrient uptake, transcription, protein synthesis and degradation, as well as metabolic pathways, in a coordinated manner that ensures that cells grow or cease growth in response to nutrient availability. The identification of specific signals and mechanisms that stimulate TOR signaling is an active and exciting field of research that has already identified nitrogen and amino acids as key regulators of TORC1 activity. The signals, as well as the cellular functions of TORC2, are far less well understood. Additional open questions in the field concern the relationships between TORC1 and TORC2, as well as the links with other nutrient-responsive pathways. Here I review the main features of TORC1 and TORC2, with a particular focus on yeasts as model organisms.

Emergency Management for Disasters in Malaysian Hotel Industry

OpenAIRE

AlBattat Ahmad Rasmi; Mat Som Ahmad Puad; Abukhalifeh Ala`a

2014-01-01

This paper aims to identify major emergencies that have the potential to place Malaysian hotels in emergency and disaster situations; investigate how hotels were prepared for emergencies, how they manage and overcome emergencies when occurred; and limitations and factors influencing successful emergency planning and adoption emergency management in Malaysian hotels. Face-to-face interview with managers from three, four and five star hotels from different backgrounds: local; regional; and Inte...

TOR Complexes and the Maintenance of Cellular Homeostasis.

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Eltschinger, Sandra; Loewith, Robbie

2016-02-01

The Target of Rapamycin (TOR) is a conserved serine/threonine (ser/thr) kinase that functions in two, distinct, multiprotein complexes called TORC1 and TORC2. Each complex regulates different aspects of eukaryote growth: TORC1 regulates cell volume and/or mass by influencing protein synthesis and turnover, while TORC2, as detailed in this review, regulates cell surface area by influencing lipid production and intracellular turgor. TOR complexes function in feedback loops, implying that downstream effectors are also likely to be involved in upstream regulation. In this regard, the notion that TORCs function primarily as mediators of cellular and organismal homeostasis is fundamentally different from the current, predominate view of TOR as a direct transducer of extracellular biotic and abiotic signals. Copyright © 2015 Elsevier Ltd. All rights reserved.

Loss of wobble uridine modification in tRNA anticodons interferes with TOR pathway signaling

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Viktor Scheidt

2014-11-01

Full Text Available Previous work in yeast has suggested that modification of tRNAs, in particular uridine bases in the anticodon wobble position (U34, is linked to TOR (target of rapamycin signaling. Hence, U34 modification mutants were found to be hypersensitive to TOR inhibition by rapamycin. To study whether this involves inappropriate TOR signaling, we examined interaction between mutations in TOR pathway genes (tip41∆, sap190∆, ppm1∆, rrd1∆ and U34 modification defects (elp3∆, kti12∆, urm1∆, ncs2∆ and found the rapamycin hypersensitivity in the latter is epistatic to drug resistance of the former. Epistasis, however, is abolished in tandem with a gln3∆ deletion, which inactivates transcription factor Gln3 required for TOR-sensitive activation of NCR (nitrogen catabolite repression genes. In line with nuclear import of Gln3 being under control of TOR and dephosphorylation by the Sit4 phosphatase, we identify novel TOR-sensitive sit4 mutations that confer rapamycin resistance and importantly, mislocalise Gln3 when TOR is inhibited. This is similar to gln3∆ cells, which abolish the rapamycin hypersensitivity of U34 modification mutants, and suggests TOR deregulation due to tRNA undermodification operates through Gln3. In line with this, loss of U34 modifications (elp3∆, urm1∆ enhances nuclear import of and NCR gene activation (MEP2, GAP1 by Gln3 when TOR activity is low. Strikingly, this stimulatory effect onto Gln3 is suppressed by overexpression of tRNAs that usually carry the U34 modifications. Collectively, our data suggest that proper TOR signaling requires intact tRNA modifications and that loss of U34 modifications impinges on the TOR-sensitive NCR branch via Gln3 misregulation.

Loss of wobble uridine modification in tRNA anticodons interferes with TOR pathway signaling.

Science.gov (United States)

Scheidt, Viktor; Jüdes, André; Bär, Christian; Klassen, Roland; Schaffrath, Raffael

2014-11-29

Previous work in yeast has suggested that modification of tRNAs, in particular uridine bases in the anticodon wobble position (U34), is linked to TOR (target of rapamycin) signaling. Hence, U34 modification mutants were found to be hypersensitive to TOR inhibition by rapamycin. To study whether this involves inappropriate TOR signaling, we examined interaction between mutations in TOR pathway genes ( tip41 ∆, sap190 ∆, ppm1 ∆, rrd1 ∆) and U34 modification defects ( elp3 ∆, kti 12∆, urm1 ∆, ncs2 ∆) and found the rapamycin hypersensitivity in the latter is epistatic to drug resistance of the former. Epistasis, however, is abolished in tandem with a gln3 ∆ deletion, which inactivates transcription factor Gln3 required for TOR-sensitive activation of NCR (nitrogen catabolite repression) genes. In line with nuclear import of Gln3 being under control of TOR and dephosphorylation by the Sit4 phosphatase, we identify novel TOR-sensitive sit4 mutations that confer rapamycin resistance and importantly, mislocalise Gln3 when TOR is inhibited. This is similar to gln3 ∆ cells, which abolish the rapamycin hypersensitivity of U34 modification mutants, and suggests TOR deregulation due to tRNA undermodification operates through Gln3. In line with this, loss of U34 modifications ( elp3 ∆, urm1 ∆) enhances nuclear import of and NCR gene activation ( MEP2 , GAP1 ) by Gln3 when TOR activity is low. Strikingly, this stimulatory effect onto Gln3 is suppressed by overexpression of tRNAs that usually carry the U34 modifications. Collectively, our data suggest that proper TOR signaling requires intact tRNA modifications and that loss of U34 modifications impinges on the TOR-sensitive NCR branch via Gln3 misregulation.

mTOR inhibition sensitizes human hepatocellular carcinoma cells to resminostat

Energy Technology Data Exchange (ETDEWEB)

Peng, Xingang, E-mail: pengxinggang26@sina.com [Department of Emergency General Surgery, The Affiliated Hospital of Qingdao University, Qingdao (China); Zhang, Donghui, E-mail: zhangdonghuiyx@sina.com [Department of Infectious Disease, Linyi People’s Hospital, Linyi (China); Li, Zhengling, E-mail: lizhenglingzz@sina.com [Department of Nursing, Tengzhou Central People’s Hospital, Tengzhou (China); Fu, Meili, E-mail: fumeilidrlinyi@tom.com [Department of Infectious Disease, Linyi People’s Hospital, Linyi (China); Liu, Haiyan, E-mail: liuhaiyanlinyi5@sina.com [Department of Nursing, Linyi People’s Hospital, Linyi (China)

2016-09-02

Histone deacetylases (HDACs) hyper-activity in hepatocellular carcinoma (HCC) is often associated with patients’ poor prognosis. Our previous study has shown that resminostat, a novel HDAC inhibitor (HDACi), activated mitochondrial permeability transition pore (mPTP)-dependent apoptosis pathway in HCC cells. Here we explored the potential resminostat resistance factor by focusing on mammalian target of rapamycin (mTOR). We showed that AZD-2014, a novel mTOR kinase inhibitor, potentiated resminostat-induced cytotoxicity and proliferation inhibition in HCC cells. Molecularly, AZD-2014 enhanced resminostat-induced mPTP apoptosis pathway activation in HCC cells. Inhibition of this apoptosis pathway, by the caspase-9 specific inhibitor Ac-LEHD-CHO, the mPTP blockers (sanglifehrin A/cyclosporine A), or by shRNA-mediated knockdown of mPTP component cyclophilin-D (Cyp-D), significantly attenuated resminostat plus AZD-2014-induced cytotoxicity and apoptosis in HCC cells. Significantly, mTOR shRNA knockdown or kinase-dead mutation (Asp-2338-Ala) also sensitized HCC cells to resminostat, causing profound cytotoxicity and apoptosis induction. Together, these results suggest that mTOR could be a primary resistance factor of resminostat. Targeted inhibition of mTOR may thus significantly sensitize HCC cells to resminostat. - Highlights: • AZD-2014 potentiates resminostat’s cytotoxicity against HCC cells. • AZD-2014 facilitates resminostat-induced HCC cell apoptosis. • AZD-2014 augments resminostat-induced mitochondrial apoptosis pathway activation. • mTOR shRNA or kinase-dead mutation significantly sensitizes HCC cells to resminostat.

Cross regulation between mTOR signaling and O-GlcNAcylation.

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Very, Ninon; Steenackers, Agata; Dubuquoy, Caroline; Vermuse, Jeanne; Dubuquoy, Laurent; Lefebvre, Tony; El Yazidi-Belkoura, Ikram

2018-06-01

The hexosamine biosynthetic pathway (HBP) integrates glucose, amino acids, fatty acids and nucleotides metabolisms for uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) synthesis. UDP-GlcNAc is the nucleotide sugar donor for O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) processes. O-GlcNAc transferase (OGT) is the enzyme which transfers the N-acetylglucosamine (O-GlcNAc) residue onto target proteins. Several studies previously showed that glucose metabolism dysregulations associated with obesity, diabetes or cancer correlated with an increase of OGT expression and global O-GlcNAcylation levels. Moreover, these diseases present an increased activation of the nutrient sensing mammalian target of rapamycin (mTOR) pathway. Other works demonstrate that mTOR regulates protein O-GlcNAcylation in cancer cells through stabilization of OGT. In this context, we studied the cross-talk between these two metabolic sensors in vivo in obese mice predisposed to diabetes and in vitro in normal and colon cancer cells. We report that levels of OGT and O-GlcNAcylation are increased in obese mice colon tissues and colon cancer cells and are associated with a higher activation of mTOR signaling. In parallel, treatments with mTOR regulators modulate OGT and O-GlcNAcylation levels in both normal and colon cancer cells. However, deregulation of O-GlcNAcylation affects mTOR signaling activation only in cancer cells. Thus, a crosstalk exists between O-GlcNAcylation and mTOR signaling in contexts of metabolism dysregulation associated to obesity or cancer.

Spoiled Onions: Exposing Malicious Tor Exit Relays

OpenAIRE

Winter, Philipp; Lindskog, Stefan

2014-01-01

Several hundred Tor exit relays together push more than 1 GiB/s of network traffic. However, it is easy for exit relays to snoop and tamper with anonymised network traffic and as all relays are run by independent volunteers, not all of them are innocuous. In this paper, we seek to expose malicious exit relays and document their actions. First, we monitored the Tor network after developing a fast and modular exit relay scanner. We implemented several scanning modules for detecting common attac...

The TOR Signaling Network in the Model Unicellular Green Alga Chlamydomonas reinhardtii

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María Esther Pérez-Pérez

2017-07-01

Full Text Available Cell growth is tightly coupled to nutrient availability. The target of rapamycin (TOR kinase transmits nutritional and environmental cues to the cellular growth machinery. TOR functions in two distinct multiprotein complexes, termed TOR complex 1 (TORC1 and TOR complex 2 (TORC2. While the structure and functions of TORC1 are highly conserved in all eukaryotes, including algae and plants, TORC2 core proteins seem to be missing in photosynthetic organisms. TORC1 controls cell growth by promoting anabolic processes, including protein synthesis and ribosome biogenesis, and inhibiting catabolic processes such as autophagy. Recent studies identified rapamycin-sensitive TORC1 signaling regulating cell growth, autophagy, lipid metabolism, and central metabolic pathways in the model unicellular green alga Chlamydomonas reinhardtii. The central role that microalgae play in global biomass production, together with the high biotechnological potential of these organisms in biofuel production, has drawn attention to the study of proteins that regulate cell growth such as the TOR kinase. In this review we discuss the recent progress on TOR signaling in algae.

Discovery and Development of ATP-Competitive mTOR Inhibitors Using Computational Approaches.

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Luo, Yao; Wang, Ling

2017-11-16

The mammalian target of rapamycin (mTOR) is a central controller of cell growth, proliferation, metabolism, and angiogenesis. This protein is an attractive target for new anticancer drug development. Significant progress has been made in hit discovery, lead optimization, drug candidate development and determination of the three-dimensional (3D) structure of mTOR. Computational methods have been applied to accelerate the discovery and development of mTOR inhibitors helping to model the structure of mTOR, screen compound databases, uncover structure-activity relationship (SAR) and optimize the hits, mine the privileged fragments and design focused libraries. Besides, computational approaches were also applied to study protein-ligand interactions mechanisms and in natural product-driven drug discovery. Herein, we survey the most recent progress on the application of computational approaches to advance the discovery and development of compounds targeting mTOR. Future directions in the discovery of new mTOR inhibitors using computational methods are also discussed. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

The TOR Signaling Network in the Model Unicellular Green Alga Chlamydomonas reinhardtii.

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Pérez-Pérez, María Esther; Couso, Inmaculada; Crespo, José L

2017-07-12

Cell growth is tightly coupled to nutrient availability. The target of rapamycin (TOR) kinase transmits nutritional and environmental cues to the cellular growth machinery. TOR functions in two distinct multiprotein complexes, termed TOR complex 1 (TORC1) and TOR complex 2 (TORC2). While the structure and functions of TORC1 are highly conserved in all eukaryotes, including algae and plants, TORC2 core proteins seem to be missing in photosynthetic organisms. TORC1 controls cell growth by promoting anabolic processes, including protein synthesis and ribosome biogenesis, and inhibiting catabolic processes such as autophagy. Recent studies identified rapamycin-sensitive TORC1 signaling regulating cell growth, autophagy, lipid metabolism, and central metabolic pathways in the model unicellular green alga Chlamydomonas reinhardtii . The central role that microalgae play in global biomass production, together with the high biotechnological potential of these organisms in biofuel production, has drawn attention to the study of proteins that regulate cell growth such as the TOR kinase. In this review we discuss the recent progress on TOR signaling in algae.

Determination and validation of mTOR kinase-domain 3D structure by homology modeling

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Lakhlili W

2015-07-01

Full Text Available Wiame Lakhlili,1 Gwénaël Chevé,2 Abdelaziz Yasri,2 Azeddine Ibrahimi1 1Laboratoire de Biotechnologie (MedBiotech, Faculté de Médecine et de Pharmacie de Rabat, Université Mohammed V de Rabat, Rabat, Morroco; 2OriBase Pharma, Cap Gamma, Parc Euromédecine, Montpellier, France Abstract: The AKT/mammalian target of rapamycin (mTOR pathway is considered as one of the commonly activated and deregulated signaling pathways in human cancer. mTOR is associated with other proteins in two molecular complexes: mTOR complex 1/Raptor and the mTOR complex 2/Rictor. Using the crystal structure of the related lipid kinase PI3Kγ, we built a model of the catalytic region of mTOR. The modeling of the three-dimensional (3D structure of the mTOR was performed by homology modeling program SWISS-MODEL. The quality and validation of the obtained model were performed using PROCHECK and PROVE softwares. The overall stereochemical property of the protein was assessed by the Ramachandran plot. The model validation was also done by docking of known inhibitors. In this paper, we describe and validate a 3D model for the mTOR catalytic site.Keywords: mTOR, homology modeling, mTOR kinase-domain, docking

Similar taste-nutrient relationships in commonly consumed Dutch and Malaysian foods.

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Teo, Pey Sze; van Langeveld, Astrid W B; Pol, Korrie; Siebelink, Els; de Graaf, Cees; Yan, See Wan; Mars, Monica

2018-06-01

Three recent studies showed that taste intensity signals nutrient content. However, current data reflects only the food patterns in Western societies. No study has yet been performed in Asian culture. The Malaysian cuisine represents a mixture of Malay, Chinese and Indian foods. This study aimed to investigate the associations between taste intensity and nutrient content in commonly consumed Dutch (NL) and Malaysian (MY) foods. Perceived intensities of sweetness, sourness, bitterness, umami, saltiness and fat sensation were assessed for 469 Dutch and 423 Malaysian commonly consumed foods representing about 83% and 88% of an individual's average daily energy intake in each respective country. We used a trained Dutch (n = 15) and Malaysian panel (n = 20) with quantitative sensory Spectrum™ 100-point rating scales and reference solutions, R1 (13-point), R2 (33-point) and R3 (67-point). Dutch and Malaysian foods had relatively low mean sourness and bitterness (Malaysian foods (15-point) was higher than that of Dutch foods (8-point). Positive associations were found between sweetness and mono- and disaccharides (R 2  = 0.67 (NL), 0.38 (MY)), between umami and protein (R 2  = 0.29 (NL), 0.26 (MY)), between saltiness and sodium (R 2  = 0.48 (NL), 0.27 (MY)), and between fat sensation and fat content (R 2  = 0.56 (NL), 0.17(MY)) in Dutch and Malaysian foods (all, p < 0.001). The associations between taste intensity and nutrient content are not different between different countries, except for fat sensation-fat content. The two dimensional basic taste-nutrient space, representing the variance and associations between tastes and nutrients, is similar between Dutch and Malaysian commonly consumed foods. Copyright © 2018 Elsevier Ltd. All rights reserved.

Inhibitors of mTOR

NARCIS (Netherlands)

Klümpen, Heinz-Josef; Beijnen, Jos H.; Gurney, Howard; Schellens, Jan H. M.

2010-01-01

Inhibitors of mammalian target of rapamycin (mTOR) have been approved for the treatment of renal cell carcinoma and appear to have a role in the treatment of other malignancies. The primary objective of this drug review is to provide pharmacokinetic and dynamic properties of the commonly used drugs

VALIDITY OF THE BRUNEL MOOD SCALE FOR USE WITH MALAYSIAN ATHLETES

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Mohamad Faizal Lan

2012-03-01

Full Text Available The aim of the present study was to investigate the factorial validity of the Brunel Mood Scale for use with Malaysian athletes. Athletes (N = 1485 athletes competing at the Malaysian Games completed the Brunel of Mood Scale (BRUMS. Confirmatory Factor Analysis (CFA results indicated a Confirmatory Fit Index (CFI of .90 and Root Mean Squared Error of Approximation (RMSEA was 0.05. The CFI was below the 0.95 criterion for acceptability and the RMSEA value was within the limits for acceptability suggested by Hu and Bentler, 1999. We suggest that results provide some support for validity of the BRUMS for use with Malaysian athletes. Given the large sample size used in the present study, descriptive statistics could be used as normative data for Malaysian athletes

Dietary interventions that reduce mTOR activity rescue autistic-like behavioral deficits in mice.

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Wu, Jiangbo; de Theije, Caroline G M; da Silva, Sofia Lopes; Abbring, Suzanne; van der Horst, Hilma; Broersen, Laus M; Willemsen, Linette; Kas, Martien; Garssen, Johan; Kraneveld, Aletta D

2017-01-01

Enhanced mammalian target of rapamycin (mTOR) signaling in the brain has been implicated in the pathogenesis of autism spectrum disorder (ASD). Inhibition of the mTOR pathway improves behavior and neuropathology in mouse models of ASD containing mTOR-associated single gene mutations. The current study demonstrated that the amino acids histidine, lysine, threonine inhibited mTOR signaling and IgE-mediated mast cell activation, while the amino acids leucine, isoleucine, valine had no effect on mTOR signaling in BMMCs. Based on these results, we designed an mTOR-targeting amino acid diet (Active 1 diet) and assessed the effects of dietary interventions with the amino acid diet or a multi-nutrient supplementation diet (Active 2 diet) on autistic-like behavior and mTOR signaling in food allergic mice and in inbred BTBR T+Itpr3tf/J mice. Cow's milk allergic (CMA) or BTBR male mice were fed a Control, Active 1, or Active 2 diet for 7 consecutive weeks. CMA mice showed reduced social interaction and increased self-grooming behavior. Both diets reversed behavioral impairments and inhibited the mTOR activity in the prefrontal cortex and amygdala of CMA mice. In BTBR mice, only Active 1 diet reduced repetitive self-grooming behavior and attenuated the mTOR activity in the prefrontal and somatosensory cortices. The current results suggest that activated mTOR signaling pathway in the brain may be a convergent pathway in the pathogenesis of ASD bridging genetic background and environmental triggers (food allergy) and that mTOR over-activation could serve as a potential therapeutic target for the treatment of ASD. Copyright © 2016. Published by Elsevier Inc.

Nuclear Security in Action at Malaysian Borders

International Nuclear Information System (INIS)

Dahlstrom Danielle

2013-01-01

''For Malaysia, trade has to be a transparent'', explained Raja Adnan, the Director General of the Malaysian Atomic Energy Licensing Board (AELB). ''Goods are imported and exported, not just between two countries, but are in transit between several countries. Nuclear security measures help to guarantee open trade and makes sure that everyone is trading responsibly,'' emphasized Adnan. Officials from AELB prepare for a joint Indonesian-Malaysian exercise in effective border control by reviewing their national standard operating procedures (SOPs) on nuclear security, which were developed in close coordination with the IAEA

Correlation between telomerase and mTOR pathway in cancer stem cells.

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Dogan, Fatma; Biray Avci, Cigir

2018-01-30

Cancer stem cells (CSCs), which are defined as a subset of tumor cells, are able to self-renew, proliferate, differentiate similar to normal stem cells. Therefore, targeting CSCs has been considered as a new approach in cancer therapy. The mammalian target of rapamycin (mTOR) is a receptor tyrosine kinase which plays an important role in regulating cell proliferation, differentiation, cell growth, self-renewal in CSCs. On the other hand, hTERT overactivation provides replicative feature and immortality to CSCs, so the stemness and replicative properties of CSCs depend on telomerase activity. Therefore hTERT/telomerase activity may become a universal biomarker for anticancer therapy and it is an attractive therapeutic target for CSCs. It is known that mTOR regulates telomerase activity at the translational and post-translational level. Researchers show that mTOR inhibitor rapamycin reduces telomerase activity without changing hTERT mRNA activity. Correlation between mTOR and hTERT is important for survival and immortality of cancer cells. In addition, the PI3K/AKT/mTOR signaling pathway and hTERT up-regulation are related with cancer stemness features and drug resistance. mTOR inhibitor and TERT inhibitor combination may construct a novel strategy in cancer stem cells and it can make a double effect on telomerase enzyme. Consequently, inhibition of PI3K/AKT/mTOR signaling pathway components and hTERT activation may prohibit CSC self-renewal and surpass CSC-mediated resistance in order to develop new cancer therapeutics. Copyright © 2017 Elsevier B.V. All rights reserved.

The Quest for Strategic Malaysian Quality National Primary School Leaders

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Ali, Hairuddin Mohd

2012-01-01

Purpose: The purpose of this paper is to investigate the nine-point strategic leadership characteristics of Malaysian Quality National Primary School Leaders (QNPSL) and to indicate the implications of these findings for the current educational management and leadership practices in their quest for Malaysian quality education.…

SPORTS WATCHING CULTURE AMONG MALAYSIANS

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Gunathevan Elumalai

2015-12-01

Full Text Available Background: Ardent sports watching will lead an individual to engage in sports and recreational activities continuously, while it also creates a sports culture among Malaysians. Sports watching culture is actually an intellectual activity. It is capable of evaluating behaviour, moral values and the level of appreciation of every spectator. Methods: This survey was conducted to identify the sports viewing culture among Malaysians. A cluster sampling method was used to select 6000 respondents from 30 million Malaysian population. Respondents were selected from urban (50% and rural areas (50%. Ethnically 56% were Malays, Sarawak and Sabah natives were 11%, Chinese 25% and finally Indians 7%. The respondents age categories were 12 to 19 years (30%, 20 to 25 years (50%, 56 and above (20%. A questionnaire developed by the research team was used to collect data. The quantitative data were analysed using Statistical Package for Social Sciences (SPSS version 21.0 for windows. Results: The findings indicate that from 5864 respondents who answered the questionnaire in full, a total of 4553 people or 77.6% watch sporting events, while a total of 1311 people or 22.4% have stated not watching any sports activities. Comparison by gender showed that 85.2% of the 2482 males watch sports events while among the female 70.2% of the 2071 watch sports events. In the category of those who do not watch, the female are higher at 29.8% than the males at 14.8%. In terms of ethnicity the Malays 80.2%. Chinese 64.6%, Indians 81.9%, natives of Sabah 94.0%, natives of Sarawak 77.6% like to watch sports events. Residential locations showed no significant differences as 78.7% of urban respondents watch sports events compared to 76.8% of rural communities. Conclusion: The findings indicated that majority of Malaysians having fun in watching sports activities. Gender still plays a role in the involvement and enjoyment of sports events either as a player or supporter. Ethnicity

Mammalian target of rapamycin (mTOR): a central regulator of male fertility?

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Jesus, Tito T; Oliveira, Pedro F; Sousa, Mário; Cheng, C Yan; Alves, Marco G

2017-06-01

Mammalian target of rapamycin (mTOR) is a central regulator of cellular metabolic phenotype and is involved in virtually all aspects of cellular function. It integrates not only nutrient and energy-sensing pathways but also actin cytoskeleton organization, in response to environmental cues including growth factors and cellular energy levels. These events are pivotal for spermatogenesis and determine the reproductive potential of males. Yet, the molecular mechanisms by which mTOR signaling acts in male reproductive system remain a matter of debate. Here, we review the current knowledge on physiological and molecular events mediated by mTOR in testis and testicular cells. In recent years, mTOR inhibition has been explored as a prime strategy to develop novel therapeutic approaches to treat cancer, cardiovascular disease, autoimmunity, and metabolic disorders. However, the physiological consequences of mTOR dysregulation and inhibition to male reproductive potential are still not fully understood. Compelling evidence suggests that mTOR is an arising regulator of male fertility and better understanding of this atypical protein kinase coordinated action in testis will provide insightful information concerning its biological significance in other tissues/organs. We also discuss why a new generation of mTOR inhibitors aiming to be used in clinical practice may also need to include an integrative view on the effects in male reproductive system.

Targeting mTOR in HIV-Negative Classic Kaposi's Sarcoma

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Ofer Merimsky

2008-01-01

Full Text Available A 66-year old female with HIV-negative classic Kaposi's sarcoma responded to mTOR targeting by rapamycin. The response was well documented by PET-CT. This case provides supporting evidence that the mTOR pathway may be important in the tumorigenesis of KS and that rapamycin may have activity in this disease.

Cap-independent translation ensures mTOR expression and function upon protein synthesis inhibition.

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Marques-Ramos, Ana; Candeias, Marco M; Menezes, Juliane; Lacerda, Rafaela; Willcocks, Margaret; Teixeira, Alexandre; Locker, Nicolas; Romão, Luísa

2017-11-01

The mechanistic/mammalian target of rapamycin (mTOR) is a conserved serine/threonine kinase that integrates cellular signals from the nutrient and energy status to act, namely, on the protein synthesis machinery. While major advances have emerged regarding the regulators and effects of the mTOR signaling pathway, little is known about the regulation of mTOR gene expression. Here, we show that the human mTOR transcript can be translated in a cap-independent manner, and that its 5' untranslated region (UTR) is a highly folded RNA scaffold capable of binding directly to the 40S ribosomal subunit. We further demonstrate that mTOR is able to bypass the cap requirement for translation both in normal and hypoxic conditions. Moreover, our data reveal that the cap-independent translation of mTOR is necessary for its ability to induce cell-cycle progression into S phase. These results suggest a novel regulatory mechanism for mTOR gene expression that integrates the global protein synthesis changes induced by translational inhibitory conditions. © 2017 Marques-Ramos et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

mTOR in breast cancer: differential expression in triple-negative and non-triple-negative tumors.

LENUS (Irish Health Repository)

Walsh, S

2012-04-01

Triple-negative breast cancer (TNBC) is defined by the absence of estrogen receptors (ER), progesterone receptors (PR) and overexpression of HER2. Targeted therapy is currently unavailable for this subgroup of breast cancer patients. mTOR controls cancer cell growth, survival and invasion and is thus a potential target for the treatment of patients with TNBC. Using immunohistochemistry, mTOR and p-mTOR were measured in 89 TNBCs and 99 non-TNBCs. While mTOR expression was confined to tumor cell cytoplasm, p-mTOR staining was located in the nucleus, perinuclear area and in the cytoplasm. Potentially important, was our finding that nuclear p-mTOR was found more frequently in triple-negative than non triple-negative cancers (p < 0.001). These results suggest that mTOR may play a more important role in the progression of TNBC compared to non-TNBC. Based on these findings, we conclude that mTOR may be a new target for the treatment of triple-negative breast cancer.

[Phenotypic diversity of toxigenic Vibrio cholerae O1 El Tor strains identified in China].

Science.gov (United States)

Zhao, Xuan; Zhang, Li; Li, Jie; Kan, Biao; Liang, Weili

2014-05-01

To understand the phenotypic diversity of toxigenic Vibrio cholerae O1 El Tor strains isolated from different provinces in China during the last 50 years. Traditional biotyping testings including susceptibility to polymyxin B, sensitivity to group IV phage, Voges-Proskauer test and haemolysis of sheep erythrocytes were conducted. Data from Biotype-specific phenotype analysis revealed that only 133 isolates carried the typical El Tor phenotypes while the other 251 isolates displayed atypical El Tor phenotypes. Combined with ctxB, rstR genotypes and phenotypic characteristics, 64 isolates were identified as typical El Tor biotype, 21 were El Tor variants that showing the typical El Tor biotype-specific phenotype but with ctxB(class). 280 isolates were defined as the hybrid groups with traits of both classical and El Tor biotypes that could be further classified into 45 groups, based on the combination of genotypes of ctxB, rstR and phenotypic characteristics. Toxigenic Vibrio cholerae O1 El Tor strains that isolated from different provinces in China displayed high phenotypic diversity. The traditional biotype traits could not be used to correctly distinguish the two different biotypes.

The role of mTOR in ovarian cancer, polycystic ovary syndrome and ovarian aging.

Science.gov (United States)

Liu, Jin; Wu, Dai-Chao; Qu, Li-Hua; Liao, Hong-Qing; Li, Mei-Xiang

2018-05-12

The mammalian target of rapamycin, mTOR, is a serine-threonine protein kinase downstream of the phosphatidylinositol 3-kinase (PI3K)-AKT axis. The pathway can regulate cell growth, proliferation, and survival by activating ribosomal kinases. Recent studies have implicated the mTOR signaling pathway in ovarian neoplasms, polycystic ovary syndrome (PCOS) and premature ovarian failure (POF). Preclinical investigations have demonstrated that the PI3K/AKT/mTOR pathway is frequently activated in the control of various ovarian functions. mTOR allows cancer cells to escape the normal biochemical system and regulates the balance between apoptosis and survival. Some recent studies have suggested that involvement of the mTOR signaling system is an important pathophysiological basis of PCOS. Overexpression of the mTOR pathway can impair the interaction of cumulus cells, lead to insulin resistance, and affect the growth of follicles directly. The roles of mTOR signaling in follicular development have been extensively studied in recent years; abnormalities in this process lead to a series of pathologies such as POF and infertility. To improve understanding of the role of the mTOR signaling pathway in the pathogenesis and development of ovarian diseases, here we review the roles of mTOR signaling in such diseases and discuss the corresponding therapeutic strategies that target this pathway. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

[Targeting of the AKT/m-TOR Pathway: Biomarkers of Resistance to Cancer Therapy--
AKT/m-TOR Pathway and Resistance to Cancer Therapy].

Science.gov (United States)

Spirina, Liudmila V; Kondakova, Irina V; Tarasenko, Natalia V; Slonimskaya, Elena M; Usynin, Evgeny A; Gorbunov, Alexey K; Yurmazov, Zahar A; Chigevskaya, Svetlana Yu

2018-01-20

Resistance to cancer therapy continues to be a major limitation for the successful treatment of cancer. There are many published studies on therapy resistance in breast and prostate cancers; however, there are currently no data on molecular markers associated with resistance. The conflicting data were reported regarding the AKT/m-TOR signaling pathway components as markers predicting resistance. The AKT/m-TOR signaling pathway is involved in the development of many human cancers; its activation is related to cell proliferation, angiogenesis, apoptosis, as well as to therapy resistance. Molecular alterations in the AKT/m-TOR signaling pathway provide a platform to identify universal markers associated with the development of resistance to cancer therapy.

PRAS40 and PRR5-like protein are new mTOR interactors that regulate apoptosis

NARCIS (Netherlands)

Thedieck, Kathrin; Polak, Pazit; Kim, Man Lyang; Molle, Klaus D; Cohen, Adiel; Jenö, Paul; Arrieumerlou, Cécile; Hall, Michael N

2007-01-01

TOR (Target of Rapamycin) is a highly conserved protein kinase and a central controller of cell growth. TOR is found in two functionally and structurally distinct multiprotein complexes termed TOR complex 1 (TORC1) and TOR complex 2 (TORC2). In the present study, we developed a two-dimensional

The nutrient transceptor/PKA pathway functions independently of TOR and responds to leucine and Gcn2 in a TOR-independent manner.

Science.gov (United States)

Conrad, Michaela; Kankipati, Harish Nag; Kimpe, Marlies; Van Zeebroeck, Griet; Zhang, Zhiqiang; Thevelein, Johan M

2017-08-01

Two nutrient-controlled signalling pathways, the PKA and TOR pathway, play a major role in nutrient regulation of growth as well as growth-correlated properties in yeast. The relationship between the two pathways is not well understood. We have used Gap1 and Pho84 transceptor-mediated activation of trehalase and phosphorylation of fragmented Sch9 as a read-out for rapid nutrient activation of PKA or TORC1, respectively. We have identified conditions in which L-citrulline-induced activation of Sch9 phosphorylation is compromised, but not activation of trehalase: addition of the TORC1 inhibitor, rapamycin and low levels of L-citrulline. The same disconnection was observed for phosphate activation in phosphate-starved cells. The leu2 auxotrophic mutation reduces amino acid activation of trehalase, which is counteracted by deletion of GCN2. Both effects were also independent of TORC1. Our results show that rapid activation of the TOR pathway by amino acids is not involved in rapid activation of the PKA pathway and that effects of Gcn2 inactivation as well as leu2 auxotrophy all act independently of the TOR pathway. Hence, rapid nutrient signalling to PKA and TOR in cells arrested by nutrient starvation acts through parallel pathways. © FEMS 2017.

The Role of mTOR Inhibitors for the Treatment of B-Cell Lymphomas

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Pinelopi Argyriou

2012-01-01

Full Text Available Despite the fact that the majority of lymphomas initially respond to treatment, many patients relapse and die from disease that is refractory to current regimens. The need for new treatment strategies in lymphomas has led to the investigation and evaluation of novel agents that target cellular pathways. The mammalian target of rapamycin (mTOR is a representative pathway that may be implicated in lymphomagenesis. Rapamycin and especially its derivatives (temsirolimus, everolimus, and deforolimus represent the first described mTOR inhibitors. These agents have shown promising results in the treatment of lymphoid malignancies. On the other hand, new ATP-competitive mTOR inhibitors that provoke a broader inhibition of mTOR activity are in early stages of clinical development. The purpose of this paper is to summarize the existing knowledge about mTOR inhibitors and their use in the treatment of B-cell lymphomas. Relevant issues regarding mTOR biology in general as well as in B-cell lymphoid neoplasms are also discussed in short.

Assessing Quality of Working Life Among Malaysian Workers.

Science.gov (United States)

Sulaiman, Nur Suffia; Choo, Wan Yuen; Mat Yassim, Abdul Rahim; Van Laar, Darren; Chinna, Karuthan; Majid, Hazreen Abdul

2015-11-01

The Work-Related Quality of Life Scale-2 (WRQLS-2) has been used to measure quality of working life (QOWL) in the United Kingdom. In this study, the scale was translated and normalized into Malay. The scale was translated using the back-translation method, pretesting, and pilot testing. It was conducted among health care and office workers. It was tested in 3 stages; confirmatory factor analysis at stages 1 and 3 and exploratory factor analysis at stage 2. The Malaysian WRQLS-2 had 5 factors: "General Well-Being," "Job and Career Satisfaction," "Employee Engagement," "Home-Work Interface," and "Stress at Work." The scale showed good convergent and construct validity and also reliability. Perception of good QOWL may differ because of cultural influences and varying work environments. The validated Malaysian WRQLS-2 can be used to determine the QOWL of Malaysian office and health care workers. © 2015 APJPH.

Traditional Postpartum Practices Among Malaysian Mothers: A Review.

Science.gov (United States)

Fadzil, Fariza; Shamsuddin, Khadijah; Wan Puteh, Sharifa Ezat

2016-07-01

To briefly describe the postpartum practices among the three major ethnic groups in Malaysia and to identify commonalities in their traditional postpartum beliefs and practices. This narrative review collated information on traditional postpartum practices among Malaysian mothers through a literature search for published research papers on traditional postpartum practices in Malaysia. This review shows that Malaysian mothers have certain postpartum practices that they considered to be important for preventing future ill health. Despite the perceived differences in intra-ethnic postpartum practices, most Malaysian mothers, although from different ethnicities, share similarities in their postpartum regimens and practices in terms of beliefs and adherence to food taboos, use of traditional postpartum massage and traditional herbs, and acknowledgment of the role of older female family members in postpartum care. Health care providers should be aware of multiethnic traditional postpartum practices and use the commonalities in these practices as part of their postpartum care regimen.

Vasopressin activates Akt/mTOR pathway in smooth muscle cells cultured in high glucose concentration

Energy Technology Data Exchange (ETDEWEB)

Montes, Daniela K.; Brenet, Marianne; Muñoz, Vanessa C.; Burgos, Patricia V.; Villanueva, Carolina I. [Department of Physiology, Universidad Austral de Chile, Valdivia 509-9200 (Chile); Figueroa, Carlos D. [Department of Anatomy, Histology and Pathology, Universidad Austral de Chile, Valdivia 509-9200 (Chile); González, Carlos B., E-mail: cbgonzal@uach.cl [Department of Physiology, Universidad Austral de Chile, Valdivia 509-9200 (Chile); Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX 77555 (United States)

2013-11-29

Highlights: •AVP induces mTOR phosphorylation in A-10 cells cultured in high glucose concentration. •The mTOR phosphorylation is mediated by the PI3K/Akt pathway activation. •The AVP-induced mTOR phosphorylation inhibited autophagy and stimulated cell proliferation. -- Abstract: Mammalian target of rapamycin (mTOR) complex is a key regulator of autophagy, cell growth and proliferation. Here, we studied the effects of arginine vasopressin (AVP) on mTOR activation in vascular smooth muscle cells cultured in high glucose concentration. AVP induced the mTOR phosphorylation in A-10 cells grown in high glucose, in contrast to cells cultured in normal glucose; wherein, only basal phosphorylation was observed. The AVP-induced mTOR phosphorylation was inhibited by a PI3K inhibitor. Moreover, the AVP-induced mTOR activation inhibited autophagy and increased thymidine incorporation in cells grown in high glucose. This increase was abolished by rapamycin which inhibits the mTORC1 complex formation. Our results suggest that AVP stimulates mTOR phosphorylation by activating the PI3K/Akt signaling pathway and, subsequently, inhibits autophagy and raises cell proliferation in A-10 cells maintained in high glucose concentration.

Public acceptance of nuclear power among Malaysian students

Science.gov (United States)

Muhamad Pauzi, Anas; Saad, Juniza Md; Arif Abu Bakar, Asyraf; Hannan Damahuri, Abdul; Syukri, Nur Syamim Mohd

2018-01-01

Malaysian government’s aim to include nuclear energy for electricity generation has triggered various reactions from all especially the public. The objective of this study is to have a better understanding on the knowledge, sources of information of nuclear power and sources of energy chosen by Malaysian in 20 years’ time. Besides that, we want to examine the level of acceptance and perception of Malaysian towards nuclear energy and we want to identify the correlation between public perceptions with the acceptance towards nuclear power in Malaysia, and also to study the differences between perception and acceptance of nuclear power with gender and educational level. For this research methodology, the research questions are given orally or through paper-pencil and also social networking site such as Facebook or through electronic media application such as WhatsApp and Google docs. The data were analysed using a SPSS version 22.0 (Statistical Package for the Social Sciences). Results showed that more than 50% of the respondents have the knowledge of nuclear energy. A part of from that, only 39 % are confident government can afford to build NPP in Malaysia and 41 % disagree nuclear energy is the best option for future energy. From analysis using SPSS 22 we estimate negative perception will give a negative acceptance in term of support towards the use of nuclear energy in power generation in Malaysia. There are also slight correlation that the higher the level of education of Malaysian, the more negative the perception of Malaysian in accepting nuclear energy as source of power in Malaysia. Therefore in shaping a positive acceptance of NPP in Malaysia, the authorities need to educate the people with the knowledge of nuclear in order to overcome the negative perception towards nuclear power.

The Malaysian experience

OpenAIRE

Aldon, E.T.

1997-01-01

Integrated farming has long been practiced in Malaysia, not only to provide protein requirements needed by the family, but also as a source of income. With fish being promoted on a larger scale, the Malaysian government is providing farmers with financial assistance and hands-on training on fish culture and rice production. Systems of fodder-fish integrated farming and fish-livestock farming in mine ponds are outlined.

GTPase ROP2 binds and promotes activation of target of rapamycin, TOR, in response to auxin.

Science.gov (United States)

Schepetilnikov, Mikhail; Makarian, Joelle; Srour, Ola; Geldreich, Angèle; Yang, Zhenbiao; Chicher, Johana; Hammann, Philippe; Ryabova, Lyubov A

2017-04-03

Target of rapamycin (TOR) promotes reinitiation at upstream ORFs (uORFs) in genes that play important roles in stem cell regulation and organogenesis in plants. Here, we report that the small GTPase ROP2, if activated by the phytohormone auxin, promotes activation of TOR, and thus translation reinitiation of uORF-containing mRNAs. Plants with high levels of active ROP2, including those expressing constitutively active ROP2 (CA-ROP2), contain high levels of active TOR ROP2 physically interacts with and, when GTP-bound, activates TOR in vitro TOR activation in response to auxin is abolished in ROP-deficient rop2 rop6 ROP4 RNAi plants. GFP-TOR can associate with endosome-like structures in ROP2-overexpressing plants, indicating that endosomes mediate ROP2 effects on TOR activation. CA-ROP2 is efficient in loading uORF-containing mRNAs onto polysomes and stimulates translation in protoplasts, and both processes are sensitive to TOR inhibitor AZD-8055. TOR inactivation abolishes ROP2 regulation of translation reinitiation, but not its effects on cytoskeleton or intracellular trafficking. These findings imply a mode of translation control whereby, as an upstream effector of TOR, ROP2 coordinates TOR function in translation reinitiation pathways in response to auxin. © 2017 The Authors.

A Legume TOR Protein Kinase Regulates Rhizobium Symbiosis and Is Essential for Infection and Nodule Development.

Science.gov (United States)

Nanjareddy, Kalpana; Blanco, Lourdes; Arthikala, Manoj-Kumar; Alvarado-Affantranger, Xóchitl; Quinto, Carmen; Sánchez, Federico; Lara, Miguel

2016-11-01

The target of rapamycin (TOR) protein kinase regulates metabolism, growth, and life span in yeast, animals, and plants in coordination with nutrient status and environmental conditions. The nutrient-dependent nature of TOR functionality makes this kinase a putative regulator of symbiotic associations involving nutrient acquisition. However, TOR's role in these processes remains to be understood. Here, we uncovered the role of TOR during the bean (Phaseolus vulgaris)-Rhizobium tropici (Rhizobium) symbiotic interaction. TOR was expressed in all tested bean tissues, with higher transcript levels in the root meristems and senesced nodules. We showed TOR promoter expression along the progressing infection thread and in the infected cells of mature nodules. Posttranscriptional gene silencing of TOR using RNA interference (RNAi) showed that this gene is involved in lateral root elongation and root cell organization and also alters the density, size, and number of root hairs. The suppression of TOR transcripts also affected infection thread progression and associated cortical cell divisions, resulting in a drastic reduction of nodule numbers. TOR-RNAi resulted in reduced reactive oxygen species accumulation and altered CyclinD1 and CyclinD3 expression, which are crucial factors for infection thread progression and nodule organogenesis. Enhanced expression of TOR-regulated ATG genes in TOR-RNAi roots suggested that TOR plays a role in the recognition of Rhizobium as a symbiont. Together, these data suggest that TOR plays a vital role in the establishment of root nodule symbiosis in the common bean. © 2016 American Society of Plant Biologists. All Rights Reserved.

TOR (target of rapamycin) is a key regulator of triacylglycerol accumulation in microalgae.

Science.gov (United States)

Imamura, Sousuke; Kawase, Yasuko; Kobayashi, Ikki; Shimojima, Mie; Ohta, Hiroyuki; Tanaka, Kan

2016-01-01

Most microalgae abundantly accumulate lipid droplets (LDs) containing triacylglycerols (TAGs) under several stress conditions, but the underlying molecular mechanism of this accumulation remains unclear. In a recent study, we found that inhibition of TOR (target of rapamycin), a highly conserved protein kinase of eukaryotes, by rapamycin resulted in TAG accumulation in microalgae, indicating that TOR negatively regulates TAG accumulation. Here, we show that formation of intracellular LDs and TAG accumulation were also induced in the unicellular green alga Chlamydomonas reinhardtii after exposure to Torin1 or AZD8055, which are novel TOR inhibitors that inhibit TOR activity in a manner different from rapamycin. These results supported quite well our previous conclusion that TOR is a central regulator of TAG accumulation in microalgae.

The Malaysian English Language Competency Dilemma: Recovering Lost Grounds through MUET.

Science.gov (United States)

Chan, Swee Heng; Wong, Bee Eng

2002-01-01

Provides insights into the Malaysian English language policy, required standards, and testing in language use in Malaysian tertiary institutions. Gives information about backwash effects in particular about institutional programs related to the teaching of English as a Second Language. (Author/VWL)

"All Abroad": Malaysians' Reasons for Seeking an Overseas-Based Doctorate

Science.gov (United States)

Tagg, Brendon

2014-01-01

This article examines the process by which nine junior Malaysian academics came to complete doctoral degrees in non-Malaysian universities. It expands the scope and refines the focus of an existing study that considered international students' experiences in New Zealand. Part of the motivation for the current study was the researcher's recognition…

Past, Present and Future of Tor Hidden Services

OpenAIRE

Müller, Konstantin

2015-01-01

Using the Internet reveals the IP addresses of both communication parties to everybody, who is able to observe the communication. Anonymity systems like Tor hide the IP addresses and the communication in such a way that the communication cannot be linked between the two parties. Tor is a low-latency anonymity network designed for interactive applications, which allows its users to stay anonymous while using the Internet, for example for Web browsing, e-mail or instant messaging...

Cortisol inhibits mTOR signaling in avascular necrosis of the femoral head.

Science.gov (United States)

Liao, Yun; Su, Rui; Zhang, Ping; Yuan, Bo; Li, Ling

2017-10-18

ANFH is a major health problem, to which long lasting and definitive treatments are lacking. The aim of this study is to study RNA alterations attributed to cortisol-induced ANFH. Rat models were stratified into three groups: in vitro group (n = 20) for molecular biological assays, control group (n = 3), and ANFH group induced using lipopolysaccharide and dexamethasone (n = 3). Bone marrow-derived endothelial progenitor cells (BM-EPCs) were extracted from the rats. An RNA expression array was performed on BM-EPCs, and enriched genes were subject to pathway analysis. In vitro studies following findings of array results were also performed using the isolated BM-EPCs. Significant alterations in mammalian target of rapamycin (mTOR) and HIF signaling pathways were identified in BM-EPCs of ANFH. By applying cortisol and dexamethasone to BM-EPCs, significant changes in mTOR and HIF elements were identified. The alteration of HIF pathways appeared to be downstream of mTOR signaling. Glucocorticoid receptor (GR) expression was related to glucocorticoid-dependent mRNA expression of mTOR/HIF genes. mTOR-dependent angiogenesis but not anabolism was the target of GR in ANFH. Inhibition of mTOR signaling also induced apoptosis of BM-EPCs via CHOP-dependent DR5 induction in response to GR stimulation. Decreased mTOR signaling in response to GR stimulation leading to downregulated HIF pathway as well as increased apoptosis could be the pathophysiology.

Mutations in the Arabidopsis Lst8 and Raptor genes encoding partners of the TOR complex, or inhibition of TOR activity decrease abscisic acid (ABA) synthesis.

Science.gov (United States)

Kravchenko, Alena; Citerne, Sylvie; Jéhanno, Isabelle; Bersimbaev, Rakhmetkazhi I; Veit, Bruce; Meyer, Christian; Leprince, Anne-Sophie

2015-11-27

The Target of Rapamycin (TOR) kinase regulates essential processes in plant growth and development by modulation of metabolism and translation in response to environmental signals. In this study, we show that abscisic acid (ABA) metabolism is also regulated by the TOR kinase. Indeed ABA hormone level strongly decreases in Lst8-1 and Raptor3g mutant lines as well as in wild-type (WT) Arabidopsis plants treated with AZD-8055, a TOR inhibitor. However the growth and germination of these lines are more sensitive to exogenous ABA. The diminished ABA hormone accumulation is correlated with lower transcript levels of ZEP, NCED3 and AAO3 biosynthetic enzymes, and higher transcript amount of the CYP707A2 gene encoding a key-enzyme in abscisic acid catabolism. These results suggest that the TOR signaling pathway is implicated in the regulation of ABA accumulation in Arabidopsis. Copyright © 2015 Elsevier Inc. All rights reserved.

Loss of mTOR-dependent macroautophagy causes autistic-like synaptic pruning deficits.

Science.gov (United States)

Tang, Guomei; Gudsnuk, Kathryn; Kuo, Sheng-Han; Cotrina, Marisa L; Rosoklija, Gorazd; Sosunov, Alexander; Sonders, Mark S; Kanter, Ellen; Castagna, Candace; Yamamoto, Ai; Yue, Zhenyu; Arancio, Ottavio; Peterson, Bradley S; Champagne, Frances; Dwork, Andrew J; Goldman, James; Sulzer, David

2014-09-03

Developmental alterations of excitatory synapses are implicated in autism spectrum disorders (ASDs). Here, we report increased dendritic spine density with reduced developmental spine pruning in layer V pyramidal neurons in postmortem ASD temporal lobe. These spine deficits correlate with hyperactivated mTOR and impaired autophagy. In Tsc2 ± ASD mice where mTOR is constitutively overactive, we observed postnatal spine pruning defects, blockade of autophagy, and ASD-like social behaviors. The mTOR inhibitor rapamycin corrected ASD-like behaviors and spine pruning defects in Tsc2 ± mice, but not in Atg7(CKO) neuronal autophagy-deficient mice or Tsc2 ± :Atg7(CKO) double mutants. Neuronal autophagy furthermore enabled spine elimination with no effects on spine formation. Our findings suggest that mTOR-regulated autophagy is required for developmental spine pruning, and activation of neuronal autophagy corrects synaptic pathology and social behavior deficits in ASD models with hyperactivated mTOR. Copyright © 2014 Elsevier Inc. All rights reserved.

Malaysian nurses' evaluation of transnational higher education courses.

Science.gov (United States)

Arunasalam, Nirmala

The internationalisation of higher education has led some UK and Australian universities to deliver transnational higher education (TNHE) post-registration top-up nursing degree courses in Malaysia. These are bridging courses that allow registered nurses to upgrade their diploma qualifications to degree level. What is not sufficiently explored in the literature is nurses' evaluation of these courses and the impact of TNHE qualifications. A hermeneutic phenomenology approach was used to explore the views of 18 Malaysian nurses from one Australian and two UK TNHE universities. Semi-structured interviews were conducted to enable the Malaysian nurses to evaluate the courses. Data were analysed by thematic analysis. Findings showed a gap between Malaysian and Western teaching and learning outlook, professional values and clinical practices. The data give important insights at a time when the aim of Malaysia's investment in TNHE courses is to attain a graduate workforce with changed mindsets and enhanced patient care.

FACTORS INFLUENCING YIELD SPREADS OF THE MALAYSIAN BONDS

Directory of Open Access Journals (Sweden)

Norliza Ahmad

2009-01-01

Full Text Available Malaysian bond market is developing rapidly but not much is understood in terms of macroeconomic factors that could influence the yield spread of the Ringgit Malaysian denominated bonds. Based on a multifactor model, this paper examines the impact of four macroeconomic factors namely: Kuala Lumpur Composite Index (KLCI, Industry Production Index (IPI, Consumer Price Index (CPI and interest rates (IR on bond yield spread of the Malaysian Government Securities (MGS and Corporate Bonds (CBs for a period from January 2001 to December 2008. The findings support the expected hypotheses that CPI and IR are the major drivers that influence the changes in MGS yield spreads. However IPI and KLCI have weak and no influence on MGS yield spreads respectively Whilst IR, CPI and IPI have significant influence on the yield spreads of CB1, CB2 and CB3, KLCI has significant influence only on the CB1 yield spread but not on CB2 and CB3 yield spreads.

General Adjustment Influence Factor of Malaysian Construction Expatriates Executives Abroad

Directory of Open Access Journals (Sweden)

Zainol Halmi

2016-01-01

Full Text Available The success of Malaysian construction companies creates an opportunity to explore abroad. Past studies have shown that the difficulty of expatriates in adjusting to a new environment is the main aspect that leads to failure of assignments. The success in implementing an overseas assignment does not solely depend on an expatriate’s technical expertise. The adjustment issues such as the interaction with the host nationals, and adaptability to the host country’s culture also exert influence on the assignment. The research was conducted to identify the influence of executive expatriate general adjustment on assignment in host countries. The objective of the study was to identify adjustment influence factors relating to general adjustment abroad. Questionnaires were sent to Malaysian expatriate executives. Sixty four Malaysian expatriate executives from Malaysian construction companies overseas were involved in this study. The findings show interaction, social and living environment influences their adjustment during expatriation. Pre-departure training preparation aspects for expatriates is a good step before their departure to host countries.

An Enhancing Security Research of Tor Anonymous Communication to Against DDos Attacks

Directory of Open Access Journals (Sweden)

Feng Tao

2017-01-01

Full Text Available Tor (The Second Onion Router is modified by the first generation onion router and known as the most prevalent anonymous communication system. According to the advantage of low latency, high confidentiality of transmission content, high security of communication channels and et al., Tor is widely used in anonymous Web browsing, instant message and so on. However, the vulnerability and blemish of Tor affect system security. An identity and Signcryption-based concurrent signature scheme was used to prevent the behaviors of attackers from inserting controlled nodes and conspiring to make DDos attacks. The integrated security of Tor system was enhanced in our scheme. In addition we have proved the scheme.

Malaysian Preparation for Nuclear Power Plant Instrumentation and Control System

International Nuclear Information System (INIS)

Mohd Idris Taib; Nurfarhana Ayuni Joha; Kamarudin Sulaiman; Izhar Abu Hussin

2011-01-01

Instrumentation and Control System is required in Nuclear Power Plant for their safe and effective operation. The system is combination and integrated from detectors, actuators, analog system as well as digital system. Current design of system definitely follows of electronic as well as computer technology, with strictly follow regulation and guideline from local regulator as well as International Atomic Energy Agency. Commercial Off-The-Shelf products are extensively used with specific nucleonic instrumentation. Malaysian experiences depend on Reactor TRIGA PUSPATI Instrumentation and Control, Power Plant Instrumentation and Control as well as Process Control System. However Malaysians have capabilities to upgrade themself from Electronics, Computers, Electrical and Mechanical based. Proposal is presented for Malaysian preparation. (author)

The Malaysian Public Procurement's Prevalent System and its Weaknesses

OpenAIRE

Rohana Othman; Husein Zakaria; Norlaili Nordin; Zamzam Shahidan; Kamaruzaman Jusoff

2010-01-01

Problem statement: This study examined the public procurement system as prevalent in the Malaysian government system of administration. Various aspects of public procurement are outlined including types and the processes that entail public procurement. This study also highlighted the weaknesses in the manual public procurement processes that are opened to potential abuse and mismanagement resulting in corruption. This study places the Malaysian Government public procurement system under the s...

Managerial Coaches, Are They Ready? The Case of Malaysian Telecommunications Industry

Science.gov (United States)

Chong, Chin Wei; Yuen, Yee Yen; Tan, Booi Chen; Zarim, Zainal Abu; Hamid, Norhasniza Abdul

2016-01-01

Purpose: This paper aims to identify the key competencies managerial coaches have and examine the significant competencies that affect coaching effectiveness in the Malaysian telecommunications industry. Design/Methodology/Approach: The unit of analysis was individual managerial coaches who were working in the Malaysian telecommunications…

Comparison of thermoregulatory responses to heat between Malaysian and Japanese males during leg immersion

Science.gov (United States)

Wijayanto, Titis; Wakabayashi, Hitoshi; Lee, Joo-Young; Hashiguchi, Nobuko; Saat, Mohamed; Tochihara, Yutaka

2011-07-01

The objective of this study was to investigate thermoregulatory responses to heat in tropical (Malaysian) and temperate (Japanese) natives, during 60 min of passive heating. Ten Japanese (mean ages: 20.8 ± 0.9 years) and ten Malaysian males (mean ages: 22.3 ± 1.6 years) with matched morphological characteristics and physical fitness participated in this study. Passive heating was induced through leg immersion in hot water (42°C) for 60 min under conditions of 28°C air temperature and 50% RH. Local sweat rate on the forehead and thigh were significantly lower in Malaysians during leg immersion, but no significant differences in total sweat rate were observed between Malaysians (86.3 ± 11.8 g m-2 h-1) and Japanese (83.2 ± 6.4 g m-2 h-1) after leg immersion. In addition, Malaysians displayed a smaller rise in rectal temperature (0.3 ± 0.1°C) than Japanese (0.7 ± 0.1°C) during leg immersion, with a greater increase in hand skin temperature. Skin blood flow was significantly lower on the forehead and forearm in Malaysians during leg immersion. No significant different in mean skin temperature during leg immersion was observed between the two groups. These findings indicated that regional differences in body sweating distribution might exist between Malaysians and Japanese during heat exposure, with more uniform distribution of local sweat rate over the whole body among tropical Malaysians. Altogether, Malaysians appear to display enhanced efficiency of thermal sweating and thermoregulatory responses in dissipating heat loss during heat loading. Thermoregulatory differences between tropical and temperate natives in this study can be interpreted as a result of heat adaptations to physiological function.

Malaysian diaspora strategies in a globalized Muslim market

DEFF Research Database (Denmark)

Fischer, Johan

2015-01-01

This paper explores Malaysia’s efforts to develop and dominate a global market in halal (literally, ‘lawful or ‘permitted’) commodities as a diaspora strategy and how Malaysian state institutions, entrepreneurs, restaurants and middle-class groups in London respond to and are affected...... and practise Malaysian diaspora strategies in the globalized market for halal products and services. This paper is based on ethnographic material from fieldwork among state institutions, entrepreneurs, restaurants and middle-class groups in Kuala Lumpur and London, namely participant observation...

An Enhancing Security Research of Tor Anonymous Communication to Against DDos Attacks

OpenAIRE

Feng Tao; Zhao Ming-Tao

2017-01-01

Tor (The Second Onion Router) is modified by the first generation onion router and known as the most prevalent anonymous communication system. According to the advantage of low latency, high confidentiality of transmission content, high security of communication channels and et al., Tor is widely used in anonymous Web browsing, instant message and so on. However, the vulnerability and blemish of Tor affect system security. An identity and Signcryption-based concurrent signature scheme was use...

Torness and Hunterston - as uneconomic as Sizewell B

International Nuclear Information System (INIS)

Jeffery, J.W.

1986-01-01

The admission by CEGB that Sizewell B would be uneconomic under conditions postulated in the evidence given by the present author at the Sizewell Inquiry, is used to show that Torness and Hunterston AGRs have almost no chance of being economic, because the large immediate increases in postulated real coal prices required to enable Torness to produce a lifetime surplus, have not materialized. The attempt of SSEB to conceal the fact that it postulated this large increase in real coal prices in order to make Torness appear to be economic, is described and exposed. The joint practice of CEGB and SSEB of discounting long-term nuclear costs so that they make no significant contribution to the final calculated unit cost is described. Finally, the recent document, explaining the SSEB's case for keeping the AGR, is analysed and characterized as 'one of the most misleading documents on the economics of nuclear power to be seriously presented to the public'. (author)

Inactivation of Tor proteins affects the dynamics of endocytic proteins ...

Indian Academy of Sciences (India)

Tor2 is an activator of the Rom2/Rho1 pathway that regulates -factor internalization. Since the recruitment of endocytic proteins such as actin-binding proteins and the amphiphysins precedes the internalization of -factor, we hypothesized that loss of Tor function leads to an alteration in the dynamics of the endocytic ...

Promotion of ovarian follicle growth following mTOR activation: synergistic effects of AKT stimulators.

Directory of Open Access Journals (Sweden)

Yuan Cheng

Full Text Available Mammalian target of rapamycin (mTOR is a serine/threonine kinase and mTOR signaling is important in regulating cell growth and proliferation. Recent studies using oocyte- and granulosa cell-specific deletion of mTOR inhibitor genes TSC1 or TSC2 demonstrated the important role of mTOR signaling in the promotion of ovarian follicle development. We now report that treatment of ovaries from juvenile mice with an mTOR activator MHY1485 stimulated mTOR, S6K1 and rpS6 phosphorylation. Culturing ovaries for 4 days with MHY1485 increased ovarian explant weights and follicle development. In vivo studies further demonstrated that pre-incubation of these ovaries with MHY1485 for 2 days, followed by allo-grafting into kidney capsules of adult ovariectomized hosts for 5 days, led to marked increases in graft weights and promotion of follicle development. Mature oocytes derived from MHY1485-activated ovarian grafts could be successfully fertilized, leading the delivery of healthy pups. We further treated ovaries with the mTOR activator together with AKT activators (PTEN inhibitor and phosphoinositol-3-kinase stimulator before grafting and found additive enhancement of follicle growth. Our studies demonstrate the ability of an mTOR activator in promoting follicle growth, leading to a potential strategy to stimulate preantral follicle growth in infertile patients.

Dietary interventions that reduce mTOR activity rescue autistic-like behavioral deficits in mice

NARCIS (Netherlands)

Wu, Jiangbo; de Theije, Caroline G M; da Silva, Sofia Lopes; Abbring, Suzanne; van der Horst, Hilma; Broersen, Laus M; Willemsen, Linette; Kas, Martien; Garssen, Johan; Kraneveld, Aletta D

Enhanced mammalian target of rapamycin (mTOR) signaling in the brain has been implicated in the pathogenesis of autism spectrum disorder (ASD). Inhibition of the mTOR pathway improves behavior and neuropathology in mouse models of ASD containing mTOR-associated single gene mutations. The current

Rapid molecular evolution across amniotes of the IIS/TOR network.

Science.gov (United States)

McGaugh, Suzanne E; Bronikowski, Anne M; Kuo, Chih-Horng; Reding, Dawn M; Addis, Elizabeth A; Flagel, Lex E; Janzen, Fredric J; Schwartz, Tonia S

2015-06-02

The insulin/insulin-like signaling and target of rapamycin (IIS/TOR) network regulates lifespan and reproduction, as well as metabolic diseases, cancer, and aging. Despite its vital role in health, comparative analyses of IIS/TOR have been limited to invertebrates and mammals. We conducted an extensive evolutionary analysis of the IIS/TOR network across 66 amniotes with 18 newly generated transcriptomes from nonavian reptiles and additional available genomes/transcriptomes. We uncovered rapid and extensive molecular evolution between reptiles (including birds) and mammals: (i) the IIS/TOR network, including the critical nodes insulin receptor substrate (IRS) and phosphatidylinositol 3-kinase (PI3K), exhibit divergent evolutionary rates between reptiles and mammals; (ii) compared with a proxy for the rest of the genome, genes of the IIS/TOR extracellular network exhibit exceptionally fast evolutionary rates; and (iii) signatures of positive selection and coevolution of the extracellular network suggest reptile- and mammal-specific interactions between members of the network. In reptiles, positively selected sites cluster on the binding surfaces of insulin-like growth factor 1 (IGF1), IGF1 receptor (IGF1R), and insulin receptor (INSR); whereas in mammals, positively selected sites clustered on the IGF2 binding surface, suggesting that these hormone-receptor binding affinities are targets of positive selection. Further, contrary to reports that IGF2R binds IGF2 only in marsupial and placental mammals, we found positively selected sites clustered on the hormone binding surface of reptile IGF2R that suggest that IGF2R binds to IGF hormones in diverse taxa and may have evolved in reptiles. These data suggest that key IIS/TOR paralogs have sub- or neofunctionalized between mammals and reptiles and that this network may underlie fundamental life history and physiological differences between these amniote sister clades.

Oxygen-Dependent Cell-to-Cell Variability in the Output of the Escherichia coli Tor Phosphorelay.

Science.gov (United States)

Roggiani, Manuela; Goulian, Mark

2015-06-15

Escherichia coli senses and responds to trimethylamine-N-oxide (TMAO) in the environment through the TorT-TorS-TorR signal transduction system. The periplasmic protein TorT binds TMAO and stimulates the hybrid kinase TorS to phosphorylate the response regulator TorR through a phosphorelay. Phosphorylated TorR, in turn, activates transcription of the torCAD operon, which encodes the proteins required for anaerobic respiration via reduction of TMAO to trimethylamine. Interestingly, E. coli respires TMAO in both the presence and absence of oxygen, a behavior that is markedly different from the utilization of other alternative electron acceptors by this bacterium. Here we describe an unusual form of regulation by oxygen for this system. While the average level of torCAD transcription is the same for aerobic and anaerobic cultures containing TMAO, the behavior across the population of cells is strikingly different under the two growth conditions. Cellular levels of torCAD transcription in aerobic cultures are highly heterogeneous, in contrast to the relatively homogeneous distribution in anaerobic cultures. Thus, oxygen regulates the variance of the output but not the mean for the Tor system. We further show that this oxygen-dependent variability stems from the phosphorelay. Trimethylamine-N-oxide (TMAO) is utilized by numerous bacteria as an electron acceptor for anaerobic respiration. In E. coli, expression of the proteins required for TMAO respiration is tightly regulated by a signal transduction system that is activated by TMAO. Curiously, although oxygen is the energetically preferred electron acceptor, TMAO is respired even in the presence of oxygen. Here we describe an interesting and unexpected form of regulation for this system in which oxygen produces highly variable expression of the TMAO utilization proteins across a population of cells without affecting the mean expression of these proteins. To our knowledge, this is the first reported example of a stimulus

Drivers for Cleaner Production in Malaysian Industry

DEFF Research Database (Denmark)

Wangel, Arne

2003-01-01

This working paper tries to piece together information on regulatory initiatives promoting cleaner production (CP) in Malaysian industry, as well as points of discussion on environmental performance in the sector. It draws upon initial data collection by the team of the research project ‘A Study...... on Promotion and Implementation of Cleaner Production Practices in Malaysian Industry - Development of a National Program and Action Plan for Promotion of Cleaner Production’, which is coordinated by Institute of Environmental and Resource Management, Universiti Teknologi Malaysia; the objective of this study...... is ‘to formulate, establish and develop a comprehensive "National Cleaner Production Promotion Program" for Malaysia’....

Perception of masculinity amongst young Malaysian men: a qualitative study of university students

OpenAIRE

Fazli Khalaf, Zahra; Low, Wah Yun; Ghorbani, Behzad; Merghati Khoei, Effat

2013-01-01

Background Perception of Masculinity plays an important role in men?s lifestyles and health behaviors. Although, the importance of masculinity has been widely discussed in men?s health literature, very little is known about the meanings of masculinity in the Malaysian setting. This research aimed to explore the meanings of masculinity among Malaysian university men. Methods This qualitative study utilized in-depth interviews with 34 young Malaysian university men, aged 20?30?years from three ...

Electrolyte profile of Malaysian mothers' milk.

Science.gov (United States)

Alaudeen, S; Muslim, N; Faridah, K; Azman, A; Arshat, H

1988-12-01

The influence of socioeconomic status (ethnicity, income and parity) on electrolyte composition (sodium and potassium) in human milk is little known. We have thus quantitatively analyzed approximately 700 samples of milk (1-90 days postpartum) obtained from healthy Malaysian mothers' (Malay, Chinese and Indians) of full term infants. Results show that the mean concentration (mmol/l) of sodium is highest (48.2+or-1.7, Mean+or-SEM) in the Malaysian mothers' colostrum and this value decreased by 30% in their transitional milk and remained constant throughout subsequent days of lactation (mature milk). Ethnically, it is found that the level of sodium in colostrum of Malay and Chinese mothers were similar while the Indian mothers' colostrum showed apparently higher value (52.7+or-3.4 mmol/l) that is statistically insignificant. The transitional milk of all 3 ethnic groups studied exhibited similar levels of sodium. On subsequent days of lactation (mature milk) the Malay mothers exhibited lowest concentration (25.9+or-2.6 mmol/l) of sodium that is significantly (P0.05) different from that of Chinese and Indian mothers. Income and parity do not significantly affect the sodium level in Malaysian mothers' milk during all stages of lactation studied. The level of potassium, however did not change significantly with days of lactation. Like sodium, potassium too was not influenced by income and parity. (Author's).

Conservation, duplication, and loss of the Tor signaling pathway in the fungal kingdom

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Heitman Joseph

2010-09-01

Full Text Available Abstract Background The nutrient-sensing Tor pathway governs cell growth and is conserved in nearly all eukaryotic organisms from unicellular yeasts to multicellular organisms, including humans. Tor is the target of the immunosuppressive drug rapamycin, which in complex with the prolyl isomerase FKBP12 inhibits Tor functions. Rapamycin is a gold standard drug for organ transplant recipients that was approved by the FDA in 1999 and is finding additional clinical indications as a chemotherapeutic and antiproliferative agent. Capitalizing on the plethora of recently sequenced genomes we have conducted comparative genomic studies to annotate the Tor pathway throughout the fungal kingdom and related unicellular opisthokonts, including Monosiga brevicollis, Salpingoeca rosetta, and Capsaspora owczarzaki. Results Interestingly, the Tor signaling cascade is absent in three microsporidian species with available genome sequences, the only known instance of a eukaryotic group lacking this conserved pathway. The microsporidia are obligate intracellular pathogens with highly reduced genomes, and we hypothesize that they lost the Tor pathway as they adapted and streamlined their genomes for intracellular growth in a nutrient-rich environment. Two TOR paralogs are present in several fungal species as a result of either a whole genome duplication or independent gene/segmental duplication events. One such event was identified in the amphibian pathogen Batrachochytrium dendrobatidis, a chytrid responsible for worldwide global amphibian declines and extinctions. Conclusions The repeated independent duplications of the TOR gene in the fungal kingdom might reflect selective pressure acting upon this kinase that populates two proteinaceous complexes with different cellular roles. These comparative genomic analyses illustrate the evolutionary trajectory of a central nutrient-sensing cascade that enables diverse eukaryotic organisms to respond to their natural

An Analysis of Malaysian Political Communication and Its Role in Electoral Process

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Saabar Suhaimee Saahar

2017-01-01

Full Text Available This paper attempts to discuss political communication in Malaysia especially after the 12th General Elections (GE12. The purpose of this study is to analyse the political efficacy or sense making process which involve analysing the techniques and creative execution that had been used by political parties and its effects on Malaysian voters. The results of GE 12 had fashioned a political tsunami that influenced many important aspects in the Malaysian political landscape, be it national and economic policies, social unity or campaign strategies. Therefore, the main focus of this paper is to discuss the elements and importance of political communication research in Malaysian political communication campaign by focusing on the aspects of creative execution, political information efficacy and sense making process and its impact on the choice of communication tools amongst Malaysian voters.

The AKT-mTOR signalling pathway in kidney cancer tissues

Science.gov (United States)

Spirina, L. V.; Usynin, Y. A.; Kondakova, I. V.; Yurmazov, Z. A.; Slonimskaya, E. M.; Kolegova, E. S.

2015-11-01

An increased expression of phospho-AKT, m-TOR, glycogen regulator GSK-3-beta and transcription inhibitor 4E-BP1 was observed in kidney cancer tissues. Tumor size growth was associated with a high level of c-Raf and low content of phospho-m-TOR. Cancer metastasis development led to a decreased PTEN and phospho-AKT expression.

mTOR inhibition sensitizes ONC201-induced anti-colorectal cancer cell activity.

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Jin, Zhe-Zhu; Wang, Wei; Fang, Di-Long; Jin, Yong-Jun

2016-09-30

We here tested the anti-colorectal cancer (CRC) activity by a first-in-class small molecule TRAIL inducer ONC201. The potential effect of mTOR on ONC201's actions was also examined. ONC201 induced moderate cytotoxicity against CRC cell lines (HT-29, HCT-116 and DLD-1) and primary human CRC cells. Significantly, AZD-8055, a mTOR kinase inhibitor, sensitized ONC201-induced cytotoxicity in CRC cells. Meanwhile, ONC201-induced TRAIL/death receptor-5 (DR-5) expression, caspase-8 activation and CRC cell apoptosis were also potentiated with AZD-8055 co-treatment. Reversely, TRAIL sequestering antibody RIK-2 or the caspase-8 specific inhibitor z-IETD-fmk attenuated AZD-8055 plus ONC201-induced CRC cell death. Further, mTOR kinase-dead mutation (Asp-2338-Ala) or shRNA knockdown significantly sensitized ONC201's activity in CRC cells, leading to profound cell death and apoptosis. On the other hand, expression of a constitutively-active S6K1 (T389E) attenuated ONC201-induced CRC cell apoptosis. For the mechanism study, we showed that ONC201 blocked Akt, but only slightly inhibited mTOR in CRC cells. Co-treatment with AZD-8055 also concurrently blocked mTOR activation. These results suggest that mTOR could be a primary resistance factor of ONC201 in CRC cells. Copyright © 2016 Elsevier Inc. All rights reserved.

Discovery and optimization of potent and selective imidazopyridine and imidazopyridazine mTOR inhibitors.

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Peterson, Emily A; Boezio, Alessandro A; Andrews, Paul S; Boezio, Christiane M; Bush, Tammy L; Cheng, Alan C; Choquette, Deborah; Coats, James R; Colletti, Adria E; Copeland, Katrina W; DuPont, Michelle; Graceffa, Russell; Grubinska, Barbara; Kim, Joseph L; Lewis, Richard T; Liu, Jingzhou; Mullady, Erin L; Potashman, Michele H; Romero, Karina; Shaffer, Paul L; Stanton, Mary K; Stellwagen, John C; Teffera, Yohannes; Yi, Shuyan; Cai, Ti; La, Daniel S

2012-08-01

mTOR is a critical regulator of cellular signaling downstream of multiple growth factors. The mTOR/PI3K/AKT pathway is frequently mutated in human cancers and is thus an important oncology target. Herein we report the evolution of our program to discover ATP-competitive mTOR inhibitors that demonstrate improved pharmacokinetic properties and selectivity compared to our previous leads. Through targeted SAR and structure-guided design, new imidazopyridine and imidazopyridazine scaffolds were identified that demonstrated superior inhibition of mTOR in cellular assays, selectivity over the closely related PIKK family and improved in vivo clearance over our previously reported benzimidazole series. Copyright © 2012. Published by Elsevier Ltd.

Remote maintenance in TOR fast reactor fuel reprocessing facility

International Nuclear Information System (INIS)

Eymery, R.; Constant, M.; Malterre, G.

1986-11-01

The TOR facility which is undergoing commissioning tests has a capacity of 5 T. HM/year which is enough for reprocessing all the Phenix fuel, with an excess capacity which is to be used for other fast reactors fuels. It is the result of enlargement and renovation of the old Marcoule pilot facility. A good load factor is expected through the use of equipment with increased reliability and easy maintenance. TOR will also be used to test new equipment developed for the large breeder fuel reprocessing plant presently in the design stage. The latter objective is specifically important for the parts of the plant involving mechanical equipment which are located in a new building: TOR 1. High reliability and flexibility will be obtained in this building thanks to the attention given to the integrated remote handling system [fr

Online Activities of Urban Malaysian Adolescents: Report of a Pilot Study

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Tan, Kok Eng; Yen Abdullah, Melissa Ng Lee; Guan Saw, Kim

2012-01-01

The literacy practices of many communities today show new ways of meaning making in the contemporary, technological and digital culture. A number of Malaysian adolescents belong to this culture. This pilot study reports the preliminary findings of a larger study aimed at describing the online activities of Malaysian adolescents. Fifty-four…

ERP and Knowledge Management Integration: The Case of Malaysian Business Firms

Science.gov (United States)

Supramaniam, Mahadevan; Kuppusamy, Mudiarasan

2010-01-01

In order to compete in a global environment, Malaysian business firms need to improve their products and services through best practices. This paper aims to investigate the critical success factors to adopt Enterprise Resource Planning (ERP) with knowledge management (KM) strategies among Malaysian business firms. In order to achieve the research…

Transient activation of mTOR following forced treadmill exercise in rats

DEFF Research Database (Denmark)

Elfving, Betina; Christensen, Tina; Ratner, Cecilia

2013-01-01

, while the induction of neurogenesis requires signaling through the VEGF receptor, Flk-1 (VEGFR-2). VEGF expression is believed to be regulated by two distinct mTOR (mammalian Target of Rapamycin)-containing multiprotein complexes mTORC1 and mTORC2, respectively. This study was initiated to investigate...... of mTOR was regulated after a single bout of exercise. In conclusion, the effect of treadmill exercise on the VEGF system is acute rather than chronic and there is a transient activation of mTOR. More studies are needed to understand whether this could be beneficial in the treatment of neuropsychiatric...

Adult "termination-of-resuscitation" (TOR)-criteria may not be suitable for children - a retrospective analysis.

Science.gov (United States)

Rotering, Victoria Maria; Trepels-Kottek, Sonja; Heimann, Konrad; Brokmann, Jörg-Christian; Orlikowsky, Thorsten; Schoberer, Mark

2016-12-07

Only a small number of patients survive out-of-hospital-cardiac-arrest (OHCA). The duration of CPR varies considerably and transportation of patients under CPR is often unsuccessful. Termination-of-resuscitation (TOR)-criteria aim to preclude futile resuscitation efforts. Our goal was to find out to which extent existing TOR-criteria can be transferred to paediatric OHCA-patients with special regard to their prognostic value. We performed a retrospective analysis of an eleven-year single centre patient cohort. 43 paediatric patients admitted to our institution after emergency-medical-system (EMS)-confirmed OHCA from 2003 to 2013 were included. Morrison's BLS- and ALS-TOR-rules as well as the Trauma-TOR-criteria by the American Association of EMS Physicians were evaluated for application in children, by calculating sensitivity, specificity, negative and positive predictive value for death-, as well as survival-prediction in our cohort. 26 patients achieved ROSC and 14 were discharged alive (n = 7 PCPC 1/2, n = 7 PCPC 5). Sensitivity for BLS-TOR-criteria predicting death was 48.3%, specificity 92.9%, the PPV 93.3% and the NPV 46.4%. ALS-TOR-criteria for death had a sensitivity of 10.3%, specificity of 100%, a PPV of 100% and an NPV of 35%. Retrospective application of the BLS-TOR-rule in our patient cohort identified the resuscitation of one later survivor as futile. ALS-TOR-criteria did not give false predictions of death. The proportion of CPRs that could have been abandoned is 48.2% for the BLS-TOR and only 10.3% for the ALS-TOR-rule. Both rules therefore appear not to be transferable to a paediatric population.

The TOR Pathway Is Involved in Adventitious Root Formation in Arabidopsis and Potato.

Science.gov (United States)

Deng, Kexuan; Dong, Pan; Wang, Wanjing; Feng, Li; Xiong, Fangjie; Wang, Kai; Zhang, Shumin; Feng, Shun; Wang, Bangjun; Zhang, Jiankui; Ren, Maozhi

2017-01-01

In the agriculture industry, adventitious root formation is a core issue of plants asexual propagation. However, the underlying molecular mechanism of adventitious root formation is far beyond understanding. In present study we found that target of rapamycin (TOR) signaling plays a key role in adventitious root formation in potato and Arabidopsis . The core components of TOR complex including TOR, RAPTOR, and LST8 are highly conserved in potato, but the seedlings of potato are insensitive to rapamycin, implying FK506 Binding Protein 12 KD (FKBP12) lost the function to bridge the interaction of rapamycin and TOR in potato. To dissect TOR signaling in potato, the rapamycin hypersensitive potato plants (BP12-OE) were engineered by introducing yeast FKBP12 ( ScFKBP12 ) into potato. We found that rapamycin can significantly attenuate the capability of adventitious root formation in BP12-OE potatoes. KU63794 (KU, an active-site TOR inhibitor) combined with rapamycin can more significantly suppress adventitious root formation of BP12-OE potato than the single treatments, such as KU63794 or rapamycin, indicating its synergistic inhibitory effects on potato adventitious root formation. Furthermore, RNA-seq data showed that many genes associated with auxin signaling pathway were altered when BP12-OE potato seedlings were treated with rapamycin + KU, suggesting that TOR may play a major role in adventitious root formation via auxin signaling. The auxin receptor mutant tir1 was sensitive to TOR inhibitors and the double and quadruple mutants including tir1afb2, tir1afb3 , and tir1afb1afb2afb3 displayed more sensitive to asTORis than single mutant tir1 . Consistently, overexpression of AtTIR1 in Arabidopsis and potato can partially overcome the inhibitory effect of asTORis and promote adventitious root formation under asTORis treatments. These observations suggest that TOR signaling regulates adventitious root formation by mediating auxin signaling in Arabidopsis and potato.

Unkempt is negatively regulated by mTOR and uncouples neuronal differentiation from growth control.

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Amélie Avet-Rochex

2014-09-01

Full Text Available Neuronal differentiation is exquisitely controlled both spatially and temporally during nervous system development. Defects in the spatiotemporal control of neurogenesis cause incorrect formation of neural networks and lead to neurological disorders such as epilepsy and autism. The mTOR kinase integrates signals from mitogens, nutrients and energy levels to regulate growth, autophagy and metabolism. We previously identified the insulin receptor (InR/mTOR pathway as a critical regulator of the timing of neuronal differentiation in the Drosophila melanogaster eye. Subsequently, this pathway has been shown to play a conserved role in regulating neurogenesis in vertebrates. However, the factors that mediate the neurogenic role of this pathway are completely unknown. To identify downstream effectors of the InR/mTOR pathway we screened transcriptional targets of mTOR for neuronal differentiation phenotypes in photoreceptor neurons. We identified the conserved gene unkempt (unk, which encodes a zinc finger/RING domain containing protein, as a negative regulator of the timing of photoreceptor differentiation. Loss of unk phenocopies InR/mTOR pathway activation and unk acts downstream of this pathway to regulate neurogenesis. In contrast to InR/mTOR signalling, unk does not regulate growth. unk therefore uncouples the role of the InR/mTOR pathway in neurogenesis from its role in growth control. We also identified the gene headcase (hdc as a second downstream regulator of the InR/mTOR pathway controlling the timing of neurogenesis. Unk forms a complex with Hdc, and Hdc expression is regulated by unk and InR/mTOR signalling. Co-overexpression of unk and hdc completely suppresses the precocious neuronal differentiation phenotype caused by loss of Tsc1. Thus, Unk and Hdc are the first neurogenic components of the InR/mTOR pathway to be identified. Finally, we show that Unkempt-like is expressed in the developing mouse retina and in neural stem

Trichomonas vaginalis Metalloproteinase Induces mTOR Cleavage of SiHa Cells

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Quan, Juan-Hua; Choi, In-Wook; Yang, Jung-Bo; Zhou, Wei; Cha, Guang-Ho; Zhou, Yu; Ryu, Jae-Sook

2014-01-01

Trichomonas vaginalis secretes a number of proteases which are suspected to be the cause of pathogenesis; however, little is understood how they manipulate host cells. The mammalian target of rapamycin (mTOR) regulates cell growth, cell proliferation, cell motility, cell survival, protein synthesis, and transcription. We detected various types of metalloproteinases including GP63 protein from T. vaginalis trophozoites, and T. vaginalis GP63 metalloproteinase was confirmed by sequencing and western blot. When SiHa cells were stimulated with live T. vaginalis, T. vaginalis excretory-secretory products (ESP) or T. vaginalis lysate, live T. vaginalis and T. vaginalis ESP induced the mTOR cleavage in both time- and parasite load-dependent manner, but T. vaginalis lysate did not. Pretreatment of T. vaginalis with a metalloproteinase inhibitor, 1,10-phenanthroline, completely disappeared the mTOR cleavage in SiHa cells. Collectively, T. vaginalis metallopeptidase induces host cell mTOR cleavage, which may be related to survival of the parasite. PMID:25548410

The role of the TOR pathway in mediating the link between nutrition and longevity.

Science.gov (United States)

Lushchak, Oleh; Strilbytska, Olha; Piskovatska, Veronika; Storey, Kenneth B; Koliada, Alexander; Vaiserman, Alexander

2017-06-01

The target of rapamycin (TOR) pathway integrates signals from extracellular and intracellular agents, such as growth factors, nutrients, mediators of energy balance, oxygen availability and other environmental cues. It allows the regulation of multiple cellular processes including protein and lipid synthesis, ribosome biogenesis, autophagy and metabolic processes. Being conserved across different phyla, TOR regulates longevity of various organisms in response to dietary conditions. In this review we described the main components of the TOR pathway and its upstream effectors and downstream processes in relation to aging. The potential contribution of the TOR pathway in lifespan-extending effects of varied dietary interventions, and the anti-aging drugs rapamycin and metformin direct or indirect regulation of TOR activity in yeasts, worms, flies and mammals are also discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

The geomorphic impact of glaciers as indicated by tors in North Sweden (Aurivaara, 68° N)

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André, Marie-Françoise

2004-02-01

Geomorphological investigations carried out on 15 tor-like features located on the Aurivaara plateau (North Sweden, 68° N) provide new insights in the greatly debated age of these landforms. Erratics and till trapped deep in the tor joints support a pre-Weichselian age for tor formation. Moreover, the occurrence of various weathering stages in allochtonous material, the joint width up to 1.5 m (requiring long-term weathering), and the frequent association of tors with pediment-like forms, suggest pre-Quaternary tor formation. The juxtaposition of fresh erratics and in situ old weathering features (mushroom rocks, concentrically weathered well-rounded corestones, and grus) indicates a predominantly cold-based regime for the Scandinavian ice sheet, with erratics carried by the overlying moving ice being repeatedly deposited on tor summits during deglaciation phases. The relationships between tors and ice action indicated for the Aurivaara plateau result in the proposal of a morphodynamical succession of five tor subtypes ranging from the preservation of well-rounded corestones still embedded in grus (suggesting negligible glacial erosion) to the almost complete removal of tor features by ice scouring. A comparison with tors in similar geological and topographical contexts from the unglaciated Dartmoor area allows a tentative evaluation of an average overall glacial erosion of 0-10 m on the northern Sweden plateaus, in sharp contrast with the 190 m overdeepening of the nearby Torneträsk basin. Thus, this case study of Swedish tors provides additional support to the recent interpretations of relict landscapes in previously glaciated areas and is in accordance with the classical «model» of glacial selective erosion established in the Nordic and Arctic mountains.

Genetic evaluation for TOR1-A (DYT1 in Brazilian patients with dystonia

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Carlos Henrique F. Camargo

2014-10-01

Full Text Available Several genes have been mapped in families or in sporadic cases of dystonia. TOR1-A (DYT1 gene was linked to isolated dystonia. Objective To associate clinical information of patients with dystonia with the TOR1-A gene mutations. Method Eighty-eight patients with dystonia in cervical area (focal, segmental, multifocal and generalized were recruited at Movement Disorders Clinic of Hospital de Clínicas of the Federal University of Paraná between June of 2008 and June of 2009. They were submitted to the clinical evaluation. DNA was extract from blood and submitted at analysis to TOR1-A mutations by PCR according standard protocols. Results Two patients had c.907GAGdel mutation on TOR1-A gene. These patients, with familial history of dystonia, started his symptoms by legs and had secondary generalization. Conclusion We can suggest that analysis for TOR1-A mutations should be performed only in patients with early onset, generalized and familial dystonia.

Malaysian growth centiles for children under six years old.

Science.gov (United States)

Bong, Yiibonn; Shariff, Asma Ahmad; Mohamed, Abdul Majid; Merican, Amir Feisal

2015-03-01

Growth references are useful for the screening, assessment and monitoring of individual children as well as for evaluating various growth promoting interventions that could possibly affect a child in early life. To determine the growth centiles of Malaysian children and to establish contemporary cross-sectional growth reference charts for height and weight from birth to 6 years of age based on a representative sample of children from Malaysia. Gender- and age-specific centile curves for height and weight were derived using the Cole's LMS method. Data for this study were retrieved from Malaysian government health clinics using a two-stage stratified random sampling technique. Assessment of nutritional status was done with the SD scores (Z-scores) of WHO 2006 standards. Boys were found to be taller and heavier than girls in this study. The median length of Malaysian children was higher than the WHO 2006 standards and CDC 2000 reference. The overall prevalence of stunting and underweight were 8.3% and 9.3%, respectively. This study presents the first large-scale initiative for local reference charts. The growth reference would enable the growth assessment of a Malaysian child compared to the average growth of children in the country. It is suggested that the use of WHO 2006 Child Growth Standards should be complemented with local reference charts for a more wholesome growth assessment.

Your choice MATor(s) : large-scale quantitative anonymity assessment of Tor path selection algorithms against structural attacks

OpenAIRE

Backes, Michael; Meiser, Sebastian; Slowik, Marcin

2015-01-01

In this paper, we present a rigorous methodology for quantifying the anonymity provided by Tor against a variety of structural attacks, i.e., adversaries that compromise Tor nodes and thereby perform eavesdropping attacks to deanonymize Tor users. First, we provide an algorithmic approach for computing the anonymity impact of such structural attacks against Tor. The algorithm is parametric in the considered path selection algorithm and is, hence, capable of reasoning about variants of Tor and...

mTOR and the health benefits of exercise.

Science.gov (United States)

Watson, Kurt; Baar, Keith

2014-12-01

Exercise is the greatest physiological stress that our bodies experience. For example, during maximal endurance exercise in elite athlete's cardiac output can increase up to 8-fold and the working muscles receive 21-times more blood each minute than at rest. Given the physiological stress associated with exercise and the adaptations that occur to handle this stress, it is not surprising that exercise training is known to prevent or effectively treat a multitude of degenerative conditions including cardiovascular disease, cancer, diabetes, depression, Alzheimer's disease, Parkinson's disease, and many others. Many of the health benefits of exercise are mediated by the mammalian/mechanistic target of rapamycin (mTOR), either in complex 1 or 2, not only within the working muscle, but also in distant tissues such as fat, liver, and brain. This review will discuss how exercise activates mTOR in diverse tissues and the ways that mTOR is important in the adaptive response that makes us bigger, stronger, and healthier as a result of exercise. Copyright © 2014 Elsevier Ltd. All rights reserved.

Saccharomyces cerevisiae FKBP12 binds Arabidopsis thaliana TOR and its expression in plants leads to rapamycin susceptibility.

Science.gov (United States)

Sormani, Rodnay; Yao, Lei; Menand, Benoît; Ennar, Najla; Lecampion, Cécile; Meyer, Christian; Robaglia, Christophe

2007-06-01

The eukaryotic TOR pathway controls translation, growth and the cell cycle in response to environmental signals such as nutrients or growth-stimulating factors. The TOR protein kinase can be inactivated by the antibiotic rapamycin following the formation of a ternary complex between TOR, rapamycin and FKBP12 proteins. The TOR protein is also found in higher plants despite the fact that they are rapamycin insensitive. Previous findings using the yeast two hybrid system suggest that the FKBP12 plant homolog is unable to form a complex with rapamycin and TOR, while the FRB domain of plant TOR is still able to bind to heterologous FKBP12 in the presence of rapamycin. The resistance to rapamycin is therefore limiting the molecular dissection of the TOR pathway in higher plants. Here we show that none of the FKBPs from the model plant Arabidopsis (AtFKBPs) is able to form a ternary complex with the FRB domain of AtTOR in the presence of rapamycin in a two hybrid system. An antibody has been raised against the AtTOR protein and binding of recombinant yeast ScFKBP12 to native Arabidopsis TOR in the presence of rapamycin was demonstrated in pull-down experiments. Transgenic lines expressing ScFKBP12 were produced and were found to display a rapamycin-dependent reduction of the primary root growth and a lowered accumulation of high molecular weight polysomes. These results further strengthen the idea that plant resistance to rapamycin evolved as a consequence of mutations in plant FKBP proteins. The production of rapamycin-sensitive plants through the expression of the ScFKBP12 protein illustrates the conservation of the TOR pathway in eukaryotes. Since AtTOR null mutants were found to be embryo lethal 1, transgenic ScFKBP12 plants will provide an useful tool for the post-embryonic study of plant TOR functions. This work also establish for the first time a link between TOR activity and translation in plant cells.

Saccharomyces cerevisiae FKBP12 binds Arabidopsis thaliana TOR and its expression in plants leads to rapamycin susceptibility

Directory of Open Access Journals (Sweden)

Meyer Christian

2007-06-01

Full Text Available Abstract Background The eukaryotic TOR pathway controls translation, growth and the cell cycle in response to environmental signals such as nutrients or growth-stimulating factors. The TOR protein kinase can be inactivated by the antibiotic rapamycin following the formation of a ternary complex between TOR, rapamycin and FKBP12 proteins. The TOR protein is also found in higher plants despite the fact that they are rapamycin insensitive. Previous findings using the yeast two hybrid system suggest that the FKBP12 plant homolog is unable to form a complex with rapamycin and TOR, while the FRB domain of plant TOR is still able to bind to heterologous FKBP12 in the presence of rapamycin. The resistance to rapamycin is therefore limiting the molecular dissection of the TOR pathway in higher plants. Results Here we show that none of the FKBPs from the model plant Arabidopsis (AtFKBPs is able to form a ternary complex with the FRB domain of AtTOR in the presence of rapamycin in a two hybrid system. An antibody has been raised against the AtTOR protein and binding of recombinant yeast ScFKBP12 to native Arabidopsis TOR in the presence of rapamycin was demonstrated in pull-down experiments. Transgenic lines expressing ScFKBP12 were produced and were found to display a rapamycin-dependent reduction of the primary root growth and a lowered accumulation of high molecular weight polysomes. Conclusion These results further strengthen the idea that plant resistance to rapamycin evolved as a consequence of mutations in plant FKBP proteins. The production of rapamycin-sensitive plants through the expression of the ScFKBP12 protein illustrates the conservation of the TOR pathway in eukaryotes. Since AtTOR null mutants were found to be embryo lethal 1, transgenic ScFKBP12 plants will provide an useful tool for the post-embryonic study of plant TOR functions. This work also establish for the first time a link between TOR activity and translation in plant cells

Framing knowledge and awareness of energy efficiency among the Malaysian public

International Nuclear Information System (INIS)

Mohammed Zin Nordin; Shanthi Balraj; Nor Azilah Ngah; Irfan Naufal Umar; Kamarulazizi Ibrahim

2006-01-01

Energy is a key component in Malaysian economy and contributes to the industrialization of the economy. Energy production in Malaysia, however, is mainly based on burning fossil fuels such as oil, gas and coal, all of which emit pollutants. Improving the energy performance of the nation and reducing overall energy consumption will lead to a meaningful environment and economic progress. The first part of the paper looks at the agenda on energy efficiency (EE) while the second part of the paper examines the Malaysian public knowledge on EE based on survey information obtained from 2,444 respondents by way of questionnaires. The study notes that in general most Malaysian have very little knowledge on energy efficiency, as it is a relatively new area to the people of Malaysia. This paper argues that education and training in raising awareness on energy efficiency (EE) is critical to the Malaysian society as we cannot be complacent with the existing sources of energy derived from crude oil and gas. The findings will chart some of the challenges confronting the country in promoting the agenda on energy efficiency

Tight tabs kept on Torness

International Nuclear Information System (INIS)

Ferguson, H.

1984-01-01

An account is given of the progress of civil engineering construction at the Torness nuclear power plant. Special reference is made to the organization of quality assurance records, through inspection and quality control at all stages of the construction, as a requirement for the licence for the plant. (U.K.)

Targeting tumorigenesis: development and use of mTOR inhibitors in cancer therapy

Directory of Open Access Journals (Sweden)

Kay Andrea

2009-10-01

Full Text Available Abstract The mammalian target of rapamycin (mTOR is an intracellular serine/threonine protein kinase positioned at a central point in a variety of cellular signaling cascades. The established involvement of mTOR activity in the cellular processes that contribute to the development and progression of cancer has identified mTOR as a major link in tumorigenesis. Consequently, inhibitors of mTOR, including temsirolimus, everolimus, and ridaforolimus (formerly deforolimus have been developed and assessed for their safety and efficacy in patients with cancer. Temsirolimus is an intravenously administered agent approved by the US Food and Drug Administration (FDA and the European Medicines Agency (EMEA for the treatment of advanced renal cell carcinoma (RCC. Everolimus is an oral agent that has recently obtained US FDA and EMEA approval for the treatment of advanced RCC after failure of treatment with sunitinib or sorafenib. Ridaforolimus is not yet approved for any indication. The use of mTOR inhibitors, either alone or in combination with other anticancer agents, has the potential to provide anticancer activity in numerous tumor types. Cancer types in which these agents are under evaluation include neuroendocrine tumors, breast cancer, leukemia, lymphoma, hepatocellular carcinoma, gastric cancer, pancreatic cancer, sarcoma, endometrial cancer, and non-small-cell lung cancer. The results of ongoing clinical trials with mTOR inhibitors, as single agents and in combination regimens, will better define their activity in cancer.

Knockdown of TOR causing ovarian diapause in a genetically stable brachypterous strain of Nilaparvata lugens.

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Liu, Fangzhou; Li, Kaiyin; Cai, Wanlun; Zhao, Jing; Zou, Yulan; Hua, Hongxia

2017-08-01

Brown planthopper (BPH), Nilaparvata lugens (Stål) (Hemiptera: Delphacidae), is one of the most damaging pests of rice crops. BPH is a migratory insect with a delayed ovarian development in migrants classified as reproductive diapause. The molecular mechanism of reproductive diapause remains unclear, although we suspect it might be regulated by one or more nutrient signaling pathways. The target of rapamycin (TOR) pathway regulates cell growth in response to nutritional information, which raised a hypothesis that TOR mediates BPH reproductive diapause. We used a pure brachypterous strain (BS) and a predominantly macropterous strain (MS) to investigate the roles of NlTOR in BPH reproductive diapause. We found that NlTOR is expressed from the nymphal to adult stages, with a higher expression level of NlTOR in BS adults at 1, 2, and 4 days posteclosion than in MS at the same time points. Injection of dsNlTOR into BS nymphs resulted in the termination of BPH female ovary development and the retardation of nymph development. We infer that TOR signaling functions in BPH reproductive diapause by regulating the expression of NlFoxA and NlVitellogenin. © 2017 Wiley Periodicals, Inc.

Take-over again: Investigating multimodal and directional TORs to get the driver back into the loop.

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Petermeijer, Sebastiaan; Bazilinskyy, Pavlo; Bengler, Klaus; de Winter, Joost

2017-07-01

When a highly automated car reaches its operational limits, it needs to provide a take-over request (TOR) in order for the driver to resume control. The aim of this simulator-based study was to investigate the effects of TOR modality and left/right directionality on drivers' steering behaviour when facing a head-on collision without having received specific instructions regarding the directional nature of the TORs. Twenty-four participants drove three sessions in a highly automated car, each session with a different TOR modality (auditory, vibrotactile, and auditory-vibrotactile). Six TORs were provided per session, warning the participants about a stationary vehicle that had to be avoided by changing lane left or right. Two TORs were issued from the left, two from the right, and two from both the left and the right (i.e., nondirectional). The auditory stimuli were presented via speakers in the simulator (left, right, or both), and the vibrotactile stimuli via a tactile seat (with tactors activated at the left side, right side, or both). The results showed that the multimodal TORs yielded statistically significantly faster steer-touch times than the unimodal vibrotactile TOR, while no statistically significant differences were observed for brake times and lane change times. The unimodal auditory TOR yielded relatively low self-reported usefulness and satisfaction ratings. Almost all drivers overtook the stationary vehicle on the left regardless of the directionality of the TOR, and a post-experiment questionnaire revealed that most participants had not realized that some of the TORs were directional. We conclude that between the three TOR modalities tested, the multimodal approach is preferred. Moreover, our results show that directional auditory and vibrotactile stimuli do not evoke a directional response in uninstructed drivers. More salient and semantically congruent cues, as well as explicit instructions, may be needed to guide a driver into a specific

Fluoxetine regulates mTOR signalling in a region-dependent manner in depression-like mice

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Liu, Xiao-Long; Luo, Liu; Mu, Rong-Hao; Liu, Bin-Bin; Geng, Di; Liu, Qing; Yi, Li-Tao

2015-01-01

Previous studies have demonstrated that the mammalian target of rapamycin (mTOR) signaling pathway has an important role in ketamine-induced, rapid antidepressant effects despite the acute administration of fluoxetine not affecting mTOR phosphorylation in the brain. However, the effects of long-term fluoxetine treatment on mTOR modulation have not been assessed to date. In the present study, we examined whether fluoxetine, a type of commonly used antidepressant agent, alters mTOR signaling following chronic administration in different brain regions, including the frontal cortex, hippocampus, amygdala and hypothalamus. We also investigated whether fluoxetine enhanced synaptic protein levels in these regions via the activation of the mTOR signaling pathway and its downstream regulators, p70S6K and 4E-BP-1. The results indicated that chronic fluoxetine treatment attenuated the chronic, unpredictable, mild stress (CUMS)-induced mTOR phosphorylation reduction in the hippocampus and amygdala of mice but not in the frontal cortex or the hypothalamus. Moreover, the CUMS-decreased PSD-95 and synapsin I levels were reversed by fluoxetine, and these effects were blocked by rapamycin only in the hippocampus. In conclusion, our findings suggest that chronic treatment with fluoxetine can induce synaptic protein expression by activating the mTOR signaling pathway in a region-dependent manner and mainly in the hippocampus. PMID:26522512

A Legume TOR Protein Kinase Regulates Rhizobium Symbiosis and Is Essential for Infection and Nodule Development1[OPEN

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Blanco, Lourdes; Quinto, Carmen

2016-01-01

The target of rapamycin (TOR) protein kinase regulates metabolism, growth, and life span in yeast, animals, and plants in coordination with nutrient status and environmental conditions. The nutrient-dependent nature of TOR functionality makes this kinase a putative regulator of symbiotic associations involving nutrient acquisition. However, TOR’s role in these processes remains to be understood. Here, we uncovered the role of TOR during the bean (Phaseolus vulgaris)-Rhizobium tropici (Rhizobium) symbiotic interaction. TOR was expressed in all tested bean tissues, with higher transcript levels in the root meristems and senesced nodules. We showed TOR promoter expression along the progressing infection thread and in the infected cells of mature nodules. Posttranscriptional gene silencing of TOR using RNA interference (RNAi) showed that this gene is involved in lateral root elongation and root cell organization and also alters the density, size, and number of root hairs. The suppression of TOR transcripts also affected infection thread progression and associated cortical cell divisions, resulting in a drastic reduction of nodule numbers. TOR-RNAi resulted in reduced reactive oxygen species accumulation and altered CyclinD1 and CyclinD3 expression, which are crucial factors for infection thread progression and nodule organogenesis. Enhanced expression of TOR-regulated ATG genes in TOR-RNAi roots suggested that TOR plays a role in the recognition of Rhizobium as a symbiont. Together, these data suggest that TOR plays a vital role in the establishment of root nodule symbiosis in the common bean. PMID:27698253

Down-regulation of mTOR leads to up-regulation of osteoprotegerin in bone marrow cells

International Nuclear Information System (INIS)

Mogi, Makio; Kondo, Ayami

2009-01-01

Osteoprotegerin (OPG)/osteoclastogenesis inhibitory factor regulates bone mass by inhibiting osteoclastic bone resorption. mTOR, which is the mammalian target of rapamycin, is a kinase and central regulator of cell growth, proliferation, and survival. By using Rapamycin, we studied whether mTOR pathway is associated with OPG protein production in the mouse bone marrow-derived stromal cell line ST2. Rapamycin markedly increased the level of soluble OPG in ST2 cells. This antibiotic treatment resulted in the suppression of phosphorylation of mTOR. Rapamycin had no effects on the proliferation, differentiation, or apoptosis of the cells. Treatment with bone morphogenetic protein-4, which can induce OPG protein in ST2 cells, also resulted in a decrease in the density of the phospho-mTOR-band, suggesting that the suppression of the phospho-mTOR pathway is necessary for OPG production in ST2 cells. Thus, suitable suppression of mTOR phosphorylation is a necessary requirement for OPG production in bone marrow stromal cells.

Inclusion in Malaysian Integrated Preschools

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Sukumaran, Sailajah; Loveridge, Judith; Green, Vanessa A.

2015-01-01

Inclusive education has been introduced through a number of policy developments in Malaysia over the last 10 years but there is little research investigating the extent and nature of inclusive education for preschoolers with special educational needs (SEN). This study surveyed both regular and special education teachers in Malaysian integrated…

Efficiency and Competition in the Malaysian Banking Market: Foreign versus Domestic Banks

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Rossazana Ab-Rahim

2017-08-01

Full Text Available The aim of this paper is to investigate efficiency performance of Malaysian banking market using data envelopment analysis approach in the context of the increasing presence of foreign banks. Specifically, two measures of efficiency are constructed, cost and profit efficiency by utilizing bank-level data of Malaysian commercial banks, over the period 2003 to 2014. The results obtained show the domestic banks are more efficient than the foreign banks counterparts for both measures of efficiency. Next, the Lerner Index approach is employed to measure competition and finally, Granger causality tests are undertaken to answer the question, does competition foster efficiency? The results of causality tests support a positive effect of competition on cost and profit efficiency of Malaysian banks. With regard to the financial liberalization, the findings imply that higher competitive pressure may be offset the market power of individual banks; however, eventually it will results in efficiency gains of Malaysian banks.

The Idea of a University: Rethinking the Malaysian Context

OpenAIRE

Wan, Chang Da; Sirat, Morshidi; Razak, Dzulkifli

2015-01-01

This article explores the idea of a university with a specific focus in the Malaysian context. We begin the article guided by these questions—“What is a university?” and “What are universities for?”—in examining the historical and conceptual development of universities. This is followed by asking a more specific question—“What are Malaysian universities for?”—in which we discussed the overarching roles of public and private universities in this developing country. Having examined the roles of...

High-throughput mutational analysis of TOR1A in primary dystonia

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Truong Daniel D

2009-03-01

Full Text Available Abstract Background Although the c.904_906delGAG mutation in Exon 5 of TOR1A typically manifests as early-onset generalized dystonia, DYT1 dystonia is genetically and clinically heterogeneous. Recently, another Exon 5 mutation (c.863G>A has been associated with early-onset generalized dystonia and some ΔGAG mutation carriers present with late-onset focal dystonia. The aim of this study was to identify TOR1A Exon 5 mutations in a large cohort of subjects with mainly non-generalized primary dystonia. Methods High resolution melting (HRM was used to examine the entire TOR1A Exon 5 coding sequence in 1014 subjects with primary dystonia (422 spasmodic dysphonia, 285 cervical dystonia, 67 blepharospasm, 41 writer's cramp, 16 oromandibular dystonia, 38 other primary focal dystonia, 112 segmental dystonia, 16 multifocal dystonia, and 17 generalized dystonia and 250 controls (150 neurologically normal and 100 with other movement disorders. Diagnostic sensitivity and specificity were evaluated in an additional 8 subjects with known ΔGAG DYT1 dystonia and 88 subjects with ΔGAG-negative dystonia. Results HRM of TOR1A Exon 5 showed high (100% diagnostic sensitivity and specificity. HRM was rapid and economical. HRM reliably differentiated the TOR1A ΔGAG and c.863G>A mutations. Melting curves were normal in 250/250 controls and 1012/1014 subjects with primary dystonia. The two subjects with shifted melting curves were found to harbor the classic ΔGAG deletion: 1 a non-Jewish Caucasian female with childhood-onset multifocal dystonia and 2 an Ashkenazi Jewish female with adolescent-onset spasmodic dysphonia. Conclusion First, HRM is an inexpensive, diagnostically sensitive and specific, high-throughput method for mutation discovery. Second, Exon 5 mutations in TOR1A are rarely associated with non-generalized primary dystonia.

The Role of PI3K/Akt/mTOR Signaling in Gastric Carcinoma

International Nuclear Information System (INIS)

Matsuoka, Tasuku; Yashiro, Masakazu

2014-01-01

The phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway is one of the key signaling pathways induced by various receptor-tyrosine kinases. Accumulating evidence shows that this pathway is an important promoter of cell growth, metabolism, survival, metastasis, and resistance to chemotherapy. Genetic alterations in the PI3K/Akt/mTOR pathway in gastric carcinoma have often been demonstrated. Many kinds of molecular targeting therapies are currently undergoing clinical testing in patients with solid tumors. However, with the exception of the ErbB2-targeting antibody, targeting agents, including PI3K/Akt/mTOR inhibitors, have not been approved for treatment of patients with gastric carcinoma. This review summarizes the current knowledge on PI3K/Akt/mTOR signaling in the pathogenesis of gastric carcinoma and the possible therapeutic targets for gastric carcinoma. Improved knowledge of the PI3K/Akt/mTOR pathway in gastric carcinoma will be useful in understanding the mechanisms of tumor development and for identifying ideal targets of anticancer therapy for gastric carcinoma

The Role of PI3K/Akt/mTOR Signaling in Gastric Carcinoma

Energy Technology Data Exchange (ETDEWEB)

Matsuoka, Tasuku [Department of Surgical Oncology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585 (Japan); Yashiro, Masakazu, E-mail: m9312510@med.osaka-cu.ac.jp [Department of Surgical Oncology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585 (Japan); Oncology Institute of Geriatrics and Medical Science, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585 (Japan)

2014-07-07

The phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway is one of the key signaling pathways induced by various receptor-tyrosine kinases. Accumulating evidence shows that this pathway is an important promoter of cell growth, metabolism, survival, metastasis, and resistance to chemotherapy. Genetic alterations in the PI3K/Akt/mTOR pathway in gastric carcinoma have often been demonstrated. Many kinds of molecular targeting therapies are currently undergoing clinical testing in patients with solid tumors. However, with the exception of the ErbB2-targeting antibody, targeting agents, including PI3K/Akt/mTOR inhibitors, have not been approved for treatment of patients with gastric carcinoma. This review summarizes the current knowledge on PI3K/Akt/mTOR signaling in the pathogenesis of gastric carcinoma and the possible therapeutic targets for gastric carcinoma. Improved knowledge of the PI3K/Akt/mTOR pathway in gastric carcinoma will be useful in understanding the mechanisms of tumor development and for identifying ideal targets of anticancer therapy for gastric carcinoma.

Innovation in small and medium sized enterprises (SMEs) in the Malaysian information technology (IT) industry

International Nuclear Information System (INIS)

Fatimah Mohd Amin

2001-01-01

The aim of this study is to examine innovative activities in small and medium enterprises (SMEs) in the Malaysian information technology (IT) industry. This study addresses three research questions: 1. What is the innovation pattern among SMEs in the Malaysian IT industry? 2. How significant is interactive learning between SMEs in the Malaysian IT industry and other agents in the innovation system? and 3. What is the role of the government in promoting innovation among SMEs in the Malaysian IT industry? Two approaches were taken to collect data for this study, that is, mail survey and face-to-face interviews. Based on findings from this study, the SMEs in the Malaysian IT industry were divided into four categories, namely, highly innovative, innovative, inventive, and non innovative. The patterns of knowledge acquisition and interactive learning vary among the different categories of firms, and on the whole, vertical linkages with suppliers were found to be the most significant. Finally, support through the provision of funding was considered to be among the most important roles of the government in promoting innovation in SMEs in the Malaysian IT industry. (author)

Innovation value chain capability in Malaysian-owned company: A theoretical framework

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Abidin, Norkisme Zainal; Suradi, Nur Riza Mohd

2014-09-01

Good quality products or services are no longer adequate to guarantee the sustainability of a company in the present competitive business. Prior research has developed various innovation models with the hope to better understand the innovativeness of the company. Due to countless definitions, indicators, factors, parameter and approaches in the study of innovation, it is difficult to ensure which one will best suit the Malaysian-owned company innovativeness. This paper aims to provide a theoretical background to support the framework of the innovation value chain capability in Malaysian-owned Company. The theoretical framework was based on the literature reviews, expert interviews and focus group study. The framework will be used to predict and assess the innovation value chain capability in Malaysian-owned company.

PRAS40 and PRR5-like protein are new mTOR interactors that regulate apoptosis.

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Kathrin Thedieck

Full Text Available TOR (Target of Rapamycin is a highly conserved protein kinase and a central controller of cell growth. TOR is found in two functionally and structurally distinct multiprotein complexes termed TOR complex 1 (TORC1 and TOR complex 2 (TORC2. In the present study, we developed a two-dimensional liquid chromatography tandem mass spectrometry (2D LC-MS/MS based proteomic strategy to identify new mammalian TOR (mTOR binding proteins. We report the identification of Proline-rich Akt substrate (PRAS40 and the hypothetical protein Q6MZQ0/FLJ14213/CAE45978 as new mTOR binding proteins. PRAS40 binds mTORC1 via Raptor, and is an mTOR phosphorylation substrate. PRAS40 inhibits mTORC1 autophosphorylation and mTORC1 kinase activity toward eIF-4E binding protein (4E-BP and PRAS40 itself. HeLa cells in which PRAS40 was knocked down were protected against induction of apoptosis by TNFalpha and cycloheximide. Rapamycin failed to mimic the pro-apoptotic effect of PRAS40, suggesting that PRAS40 mediates apoptosis independently of its inhibitory effect on mTORC1. Q6MZQ0 is structurally similar to proline rich protein 5 (PRR5 and was therefore named PRR5-Like (PRR5L. PRR5L binds specifically to mTORC2, via Rictor and/or SIN1. Unlike other mTORC2 members, PRR5L is not required for mTORC2 integrity or kinase activity, but dissociates from mTORC2 upon knock down of tuberous sclerosis complex 1 (TSC1 and TSC2. Hyperactivation of mTOR by TSC1/2 knock down enhanced apoptosis whereas PRR5L knock down reduced apoptosis. PRR5L knock down reduced apoptosis also in mTORC2 deficient cells. The above suggests that mTORC2-dissociated PRR5L may promote apoptosis when mTOR is hyperactive. Thus, PRAS40 and PRR5L are novel mTOR-associated proteins that control the balance between cell growth and cell death.

A perspective of the Malaysian highway energy consumption and future power supply

International Nuclear Information System (INIS)

Saqr, Khalid M.; Musa, Md. Nor

2011-01-01

In this short communication, we discuss the energy consumption trends in the Malaysian road transport sector, with a special emphasis on the energy losses due to vehicle aerodynamic drag on highways. The recent trends of energy consumption in the Malaysian road transport sector are reviewed. It is evidently shown that the aerodynamic losses represented exceed 1.2 MTOE annually since 2002. A novel concept of vertical-axis wind turbine (VAWT) farms for harvesting aerodynamic energy losses on Malaysian highways is preliminarily proposed. The novel concept aims at providing a sustainable and green energy source for the lighting of the highway network in the country.

mTOR drives cerebral blood flow and memory deficits in LDLR-/- mice modeling atherosclerosis and vascular cognitive impairment.

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Jahrling, Jordan B; Lin, Ai-Ling; DeRosa, Nicholas; Hussong, Stacy A; Van Skike, Candice E; Girotti, Milena; Javors, Martin; Zhao, Qingwei; Maslin, Leigh Ann; Asmis, Reto; Galvan, Veronica

2018-01-01

We recently showed that mTOR attenuation blocks progression and abrogates established cognitive deficits in Alzheimer's disease (AD) mouse models. These outcomes were associated with the restoration of cerebral blood flow (CBF) and brain vascular density (BVD) resulting from relief of mTOR inhibition of NO release. Recent reports suggested a role of mTOR in atherosclerosis. Because mTOR drives aging and vascular dysfunction is a universal feature of aging, we hypothesized that mTOR may contribute to brain vascular and cognitive dysfunction associated with atherosclerosis. We measured CBF, BVD, cognitive function, markers of inflammation, and parameters of cardiovascular disease in LDLR -/- mice fed maintenance or high-fat diet ± rapamycin. Cardiovascular pathologies were proportional to severity of brain vascular dysfunction. Aortic atheromas were reduced, CBF and BVD were restored, and cognitive dysfunction was attenuated potentially through reduction in systemic and brain inflammation following chronic mTOR attenuation. Our studies suggest that mTOR regulates vascular integrity and function and that mTOR attenuation may restore neurovascular function and cardiovascular health. Together with our previous studies in AD models, our data suggest mTOR-driven vascular damage may be a mechanism shared by age-associated neurological diseases. Therefore, mTOR attenuation may have promise for treatment of cognitive impairment in atherosclerosis.

Factors for analysing and improving performance of R&D in Malaysian universities

NARCIS (Netherlands)

Ramli, Mohammad Shakir; de Boer, S.J.; de Bruijn, E.J.

2004-01-01

This paper presents a model for analysing and improving performance of R&D in Malaysian universities. There are various general models for R&D analysis, but none is specific for improving the performance of R&D in Malaysian universities. This research attempts to fill a gap in the body of knowledge

Novel nervous and multi-system regenerative therapeutic strategies for diabetes mellitus with mTOR

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Kenneth Maiese

2016-01-01

Full Text Available Throughout the globe, diabetes mellitus (DM is increasing in incidence with limited therapies presently available to prevent or resolve the significant complications of this disorder. DM impacts multiple organs and affects all components of the central and peripheral nervous systems that can range from dementia to diabetic neuropathy. The mechanistic target of rapamycin (mTOR is a promising agent for the development of novel regenerative strategies for the treatment of DM. mTOR and its related signaling pathways impact multiple metabolic parameters that include cellular metabolic homeostasis, insulin resistance, insulin secretion, stem cell proliferation and differentiation, pancreatic β-cell function, and programmed cell death with apoptosis and autophagy. mTOR is central element for the protein complexes mTOR Complex 1 (mTORC1 and mTOR Complex 2 (mTORC2 and is a critical component for a number of signaling pathways that involve phosphoinositide 3-kinase (PI 3-K, protein kinase B (Akt, AMP activated protein kinase (AMPK, silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae (SIRT1, Wnt1 inducible signaling pathway protein 1 (WISP1, and growth factors. As a result, mTOR represents an exciting target to offer new clinical avenues for the treatment of DM and the complications of this disease. Future studies directed to elucidate the delicate balance mTOR holds over cellular metabolism and the impact of its broad signaling pathways should foster the translation of these targets into effective clinical regimens for DM.

Comment on "A dynamic network model of mTOR signaling reveals TSC-independent mTORC2 regulation": building a model of the mTOR signaling network with a potentially faulty tool.

Science.gov (United States)

Manning, Brendan D

2012-07-10

In their study published in Science Signaling (Research Article, 27 March 2012, DOI: 10.1126/scisignal.2002469), Dalle Pezze et al. tackle the dynamic and complex wiring of the signaling network involving the protein kinase mTOR, which exists within two distinct protein complexes (mTORC1 and mTORC2) that differ in their regulation and function. The authors use a combination of immunoblotting for specific phosphorylation events and computational modeling. The primary experimental tool employed is to monitor the autophosphorylation of mTOR on Ser(2481) in cell lysates as a surrogate for mTOR activity, which the authors conclude is a specific readout for mTORC2. However, Ser(2481) phosphorylation occurs on both mTORC1 and mTORC2 and will dynamically change as the network through which these two complexes are connected is manipulated. Therefore, models of mTOR network regulation built using this tool are inherently imperfect and open to alternative explanations. Specific issues with the main conclusion made in this study, involving the TSC1-TSC2 (tuberous sclerosis complex 1 and 2) complex and its potential regulation of mTORC2, are discussed here. A broader goal of this Letter is to clarify to other investigators the caveats of using mTOR Ser(2481) phosphorylation in cell lysates as a specific readout for either of the two mTOR complexes.

Speech Disfluencies and Mispronunciations in English Oral Communication among Malaysian Undergraduates

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Sarah Yong Enxhi

2012-11-01

Full Text Available The common perception of Malaysians is that they are unable to speak fluently and communicate effectively in the English language as most Malaysians do not speak English as their first language. In a country that is full of diversity in terms of race and culture, it is only natural for Malaysians to be influenced by their first language when using English as their second language. This, however, creates a problem for undergraduates who are looking for job opportunities in both local and international companies because a potential employee’s ability to communicate smoothly in English is an important criteria used by employers. This study intends to shed light on the occurrence of speech disfluencies and mispronunciations among undergraduates of a Malaysian university as well as to provide an explanation for those mispronunciations by comparing the phonetic system of the English language with the Malay and Mandarin language. With the results of this study, it is hoped that actions and measures can be taken by the academic authorities and other relevant parties to gradually improve the oral proficiency skills of undergraduates and help them to be more marketable in the future.

Evolutionary Conservation of the Components in the TOR Signaling Pathways.

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Tatebe, Hisashi; Shiozaki, Kazuhiro

2017-11-01

Target of rapamycin (TOR) is an evolutionarily conserved protein kinase that controls multiple cellular processes upon various intracellular and extracellular stimuli. Since its first discovery, extensive studies have been conducted both in yeast and animal species including humans. Those studies have revealed that TOR forms two structurally and physiologically distinct protein complexes; TOR complex 1 (TORC1) is ubiquitous among eukaryotes including animals, yeast, protozoa, and plants, while TOR complex 2 (TORC2) is conserved in diverse eukaryotic species other than plants. The studies have also identified two crucial regulators of mammalian TORC1 (mTORC1), Ras homolog enriched in brain (RHEB) and RAG GTPases. Of these, RAG regulates TORC1 in yeast as well and is conserved among eukaryotes with the green algae and land plants as apparent exceptions. RHEB is present in various eukaryotes but sporadically missing in multiple taxa. RHEB, in the budding yeast Saccharomyces cerevisiae , appears to be extremely divergent with concomitant loss of its function as a TORC1 regulator. In this review, we summarize the evolutionarily conserved functions of the key regulatory subunits of TORC1 and TORC2, namely RAPTOR, RICTOR, and SIN1. We also delve into the evolutionary conservation of RHEB and RAG and discuss the conserved roles of these GTPases in regulating TORC1.

Malaysian mental health law.

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Khan, Nusrat N; Yahya, Badi'ah; Abu Bakar, Abd Kadir; Ho, Roger C

2015-05-01

The Malaysian Mental Health Act 2001 did not come into effect until the Mental Health Regulations 2010 came into force. The Act provides a framework for the delivery of comprehensive care, treatment, control, protection and rehabilitation of those with mental disorders. The Act governs the establishment of private and government psychiatric hospitals, psychiatric nursing homes and community mental health centres. This paper outlines the provisions of the Act and the Regulations.

Hypothalamic mTOR pathway mediates thyroid hormone-induced hyperphagia in hyperthyroidism.

Science.gov (United States)

Varela, Luis; Martínez-Sánchez, Noelia; Gallego, Rosalía; Vázquez, María J; Roa, Juan; Gándara, Marina; Schoenmakers, Erik; Nogueiras, Rubén; Chatterjee, Krishna; Tena-Sempere, Manuel; Diéguez, Carlos; López, Miguel

2012-06-01

Hyperthyroidism is characterized in rats by increased energy expenditure and marked hyperphagia. Alterations of thermogenesis linked to hyperthyroidism are associated with dysregulation of hypothalamic AMPK and fatty acid metabolism; however, the central mechanisms mediating hyperthyroidism-induced hyperphagia remain largely unclear. Here, we demonstrate that hyperthyroid rats exhibit marked up-regulation of the hypothalamic mammalian target of rapamycin (mTOR) signalling pathway associated with increased mRNA levels of agouti-related protein (AgRP) and neuropeptide Y (NPY), and decreased mRNA levels of pro-opiomelanocortin (POMC) in the arcuate nucleus of the hypothalamus (ARC), an area where mTOR co-localizes with thyroid hormone receptor-α (TRα). Central administration of thyroid hormone (T3) or genetic activation of thyroid hormone signalling in the ARC recapitulated hyperthyroidism effects on feeding and the mTOR pathway. In turn, central inhibition of mTOR signalling with rapamycin in hyperthyroid rats reversed hyperphagia and normalized the expression of ARC-derived neuropeptides, resulting in substantial body weight loss. The data indicate that in the hyperthyroid state, increased feeding is associated with thyroid hormone-induced up-regulation of mTOR signalling. Furthermore, our findings that different neuronal modulations influence food intake and energy expenditure in hyperthyroidism pave the way for a more rational design of specific and selective therapeutic compounds aimed at reversing the metabolic consequences of this disease. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Molecular insights into the evolutionary pathway of Vibrio cholerae O1 atypical El Tor variants.

Science.gov (United States)

Kim, Eun Jin; Lee, Dokyung; Moon, Se Hoon; Lee, Chan Hee; Kim, Sang Jun; Lee, Jae Hyun; Kim, Jae Ouk; Song, Manki; Das, Bhabatosh; Clemens, John D; Pape, Jean William; Nair, G Balakrish; Kim, Dong Wook

2014-09-01

Pandemic V. cholerae strains in the O1 serogroup have 2 biotypes: classical and El Tor. The classical biotype strains of the sixth pandemic, which encode the classical type cholera toxin (CT), have been replaced by El Tor biotype strains of the seventh pandemic. The prototype El Tor strains that produce biotype-specific cholera toxin are being replaced by atypical El Tor variants that harbor classical cholera toxin. Atypical El Tor strains are categorized into 2 groups, Wave 2 and Wave 3 strains, based on genomic variations and the CTX phage that they harbor. Whole-genome analysis of V. cholerae strains in the seventh cholera pandemic has demonstrated gradual changes in the genome of prototype and atypical El Tor strains, indicating that atypical strains arose from the prototype strains by replacing the CTX phages. We examined the molecular mechanisms that effected the emergence of El Tor strains with classical cholera toxin-carrying phage. We isolated an intermediary V. cholerae strain that carried two different CTX phages that encode El Tor and classical cholera toxin, respectively. We show here that the intermediary strain can be converted into various Wave 2 strains and can act as the source of the novel mosaic CTX phages. These results imply that the Wave 2 and Wave 3 strains may have been generated from such intermediary strains in nature. Prototype El Tor strains can become Wave 3 strains by excision of CTX-1 and re-equipping with the new CTX phages. Our data suggest that inter-chromosomal recombination between 2 types of CTX phages is possible when a host bacterial cell is infected by multiple CTX phages. Our study also provides molecular insights into population changes in V. cholerae in the absence of significant changes to the genome but by replacement of the CTX prophage that they harbor.

mTOR pathway inhibition prevents neuroinflammation and neuronal death in a mouse model of cerebral palsy.

Science.gov (United States)

Srivastava, Isha N; Shperdheja, Jona; Baybis, Marianna; Ferguson, Tanya; Crino, Peter B

2016-01-01

Mammalian target of rapamycin (mTOR) pathway signaling governs cellular responses to hypoxia and inflammation including induction of autophagy and cell survival. Cerebral palsy (CP) is a neurodevelopmental disorder linked to hypoxic and inflammatory brain injury however, a role for mTOR modulation in CP has not been investigated. We hypothesized that mTOR pathway inhibition would diminish inflammation and prevent neuronal death in a mouse model of CP. Mouse pups (P6) were subjected to hypoxia-ischemia and lipopolysaccharide-induced inflammation (HIL), a model of CP causing neuronal injury within the hippocampus, periventricular white matter, and neocortex. mTOR pathway inhibition was achieved with rapamycin (an mTOR inhibitor; 5mg/kg) or PF-4708671 (an inhibitor of the downstream p70S6kinase, S6K, 75 mg/kg) immediately following HIL, and then for 3 subsequent days. Phospho-activation of the mTOR effectors p70S6kinase and ribosomal S6 protein and expression of hypoxia inducible factor 1 (HIF-1α) were assayed. Neuronal cell death was defined with Fluoro-Jade C (FJC) and autophagy was measured using Beclin-1 and LC3II expression. Iba-1 labeled, activated microglia were quantified. Neuronal death, enhanced HIF-1α expression, and numerous Iba-1 labeled, activated microglia were evident at 24 and 48 h following HIL. Basal mTOR signaling, as evidenced by phosphorylated-S6 and -S6K levels, was unchanged by HIL. Rapamycin or PF-4,708,671 treatment significantly reduced mTOR signaling, neuronal death, HIF-1α expression, and microglial activation, coincident with enhanced expression of Beclin-1 and LC3II, markers of autophagy induction. mTOR pathway inhibition prevented neuronal death and diminished neuroinflammation in this model of CP. Persistent mTOR signaling following HIL suggests a failure of autophagy induction, which may contribute to neuronal death in CP. These results suggest that mTOR signaling may be a novel therapeutic target to reduce neuronal cell death in

Teachers' Perception of Mobile Edutainment for Special Needs Learners: The Malaysian Case

Science.gov (United States)

Mohd Yusof, Anuar; Daniel, Esther Gnanamalar Sarojini; Low, Wah Yun; Ab. Aziz, Kamarulzaman

2014-01-01

Study of Malaysian adoption of mobile learning (m-learning) is still in the early stages. However, there are numerous researchers in the country exploring the potential and application of m-learning in the Malaysian education system, including special education. A key question is whether teachers are prepared to incorporate mobile technology as…

Identification of a Non-Gatekeeper Hot Spot for Drug-Resistant Mutations in mTOR Kinase.

Science.gov (United States)

Wu, Tzung-Ju; Wang, Xiaowen; Zhang, Yanjie; Meng, Linghua; Kerrigan, John E; Burley, Stephen K; Zheng, X F Steven

2015-04-21

Protein kinases are therapeutic targets for human cancer. However, "gatekeeper" mutations in tyrosine kinases cause acquired clinical resistance, limiting long-term treatment benefits. mTOR is a key cancer driver and drug target. Numerous small-molecule mTOR kinase inhibitors have been developed, with some already in human clinical trials. Given our clinical experience with targeted therapeutics, acquired drug resistance in mTOR is thought likely, but not yet documented. Herein, we describe identification of a hot spot (L2185) for drug-resistant mutations, which is distinct from the gatekeeper site, and a chemical scaffold refractory to drug-resistant mutations. We also provide new insights into mTOR kinase structure and function. The hot spot mutations are potentially useful as surrogate biomarkers for acquired drug resistance in ongoing clinical trials and future treatments and for the design of the next generation of mTOR-targeted drugs. Our study provides a foundation for further research into mTOR kinase function and targeting. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Radiological emergency: Malaysian preparedness and response

International Nuclear Information System (INIS)

Yusof, M. A. W.; Ali, H. M.

2011-01-01

Planning and preparation in advance for radiological emergencies can help to minimise potential public health and environmental threats if and when an actual emergency occurs. During the planning process, emergency response organisations think through how they would respond to each type of incident and the resources that will be needed. In Malaysia, planning, preparation for and response to radiological emergencies involve many parties. In the event of a radiological emergency and if it is considered a disaster, the National Security Council, the Atomic Energy Licensing Board and the Malaysian Nuclear Agency (Nuclear Malaysia) will work together with other federal agencies, state and local governments, first responders and international organisations to monitor the situation, contain the release, and clean up the contaminated site. Throughout the response, these agencies use their protective action guidelines. This paper discusses Malaysian preparedness for, and response to, any potential radiological emergency. (authors)

mTOR Inhibition and Tuberous Sclerosis Prevention

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J Gordon Millichap

2013-09-01

Full Text Available Investigators at Children's Memorial Health Institute, Warsaw, Poland, report monozygotic twin sisters with tuberous sclerosis complex (TSC, one treated with the mTOR inhibitor everolimus since age 4 years.

Inter-Religious Dialogue: The Perspective of Malaysian Contemporary Muslim Thinkers

OpenAIRE

AEMY ELYANI MAT ZAIN; JAFFARY AWANG; IDRIS ZAKARIA

2014-01-01

Malaysia is a country that is rich for the diversity of its people. This diversity can be seen from the aspect of faith, ethnicity, language, culture, and so on. In facing a society that is pluralistic in nature, several initiatives have been taken by the government and non-government bodies in ensuring understanding and unity among Malaysians. Among the initiatives taken are interreligious dialogues. In this regard, many among Malaysian thinkers have proposed some approaches and concepts of ...

Control Management and Business Performances: The Malaysian Family SMEs Perspectives

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Edward Wong Sek Khin

2015-06-01

Full Text Available This study examined the relationship between control management and family business performance in the Malaysian context. It has two objectives, the first being to determine the relationship of organizational credit control policy and procedures, employee development and motivation, and intelligence collection systems to subsequent collection reports in Malaysian family SMEs. The second objective is to investigate the moderating effect of participation in decision-making and work effort towards innovation and business performance. This is a descriptive study involving 90 senior executives employed in 90 Malaysian family SMEs/firms. A correlation analysis from this study confirmed previous researchers’ observations that high-level organizational commitment to credit control management is linked to improvements in business performance. The results suggest that three components – credit policy, employee development, and intelligence collection systems – are the most important predictors for the efficiency and effectiveness of credit control management.    

Factors Affecting Hypertension among the Malaysian Elderly

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Sima Ataollahi Eshkoor

2016-03-01

Full Text Available Hypertension is a common chronic disease in the elderly. This study aimed to determine the effects of age, ethnicity, gender, education, marital status, nutritional parameters, and blood elements on the risk of high blood pressure in the Malaysian elderly. This research was conducted on a group of 2322 non-institutionalized Malaysian elderly. The hierarchy binary logistic regression analysis was applied to estimate the risk of hypertension in respondents. Approximately, 45.61% of subjects had hypertension. The findings indicated that the female gender (Odds ratio (OR = 1.54, an increase in body weight (OR = 1.61, and an increase in the blood levels of albumin (OR = 1.51, glucose (OR = 1.92, and triglycerides (OR = 1.27 significantly increased the risk of hypertension in subjects (p < 0.05. Conversely, an increase in both dietary carbohydrates (OR = 0.74, and blood cholesterol level (OR = 0.42 significantly reduced the risk of hypertension in samples (p < 0.05. Furthermore, the results showed that ethnicity was a non-relevant factor to increase the risk of hypertension in subjects. It was concluded that female gender, an increase in body weight, and an increase in the blood levels of glucose, triglycerides, and albumin enhanced the risk of high blood pressure in the Malaysian elderly. In addition, an increase in both dietary carbohydrates and blood cholesterol level decreased hypertension in subjects.

Belongingness in the workplace: a study of Malaysian nurses' experiences.

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Mohamed, Z; Newton, J M; McKenna, L

2014-03-01

The need to belong has been proposed as the most basic need for human psychological well-being. Lack of belongingness has been associated with stress, anxiety and lack of esteem. Social and psychological functioning in the workplace has been linked to nurses' interconnection with others and their perceptions of belongingness. To explore factors contributing to Malaysian nurses' sense of belonging in the workplace. A descriptive questionnaire survey of registered nurses (n = 437) working in two Malaysian hospitals was conducted in 2011. Previously validated questionnaires translated into the Malay language were used. Data were analysed using SPSS 19.0. Nurses enhanced their sense of belonging through acceptance, 'fitting in', respect and group harmony. There were no specific demographic factors contributing to the nurses' perceptions. The findings suggest that these priorities for belongingness were contextually influenced by factors such as elements of Malaysian culture, the nature of nurses' teamwork and stereotypical values on the nursing profession. Data were collected in only two hospitals. Experiences of nurses in other hospitals and areas of Malaysia may not be similar. The influence of Malaysian culture in this study raises issues about utilization of a measurement scale developed in Western cultures, which may not directly accord with cultural values of an Eastern ethnicity. Aspects of belongingness in Malaysian nurses reflect those of nurses elsewhere. However, there are specific cultural influences at play. Therefore, development of a measurement scale based on Eastern culture would help in increasing understanding of workplace practices among these groups. Workplaces that perpetuate an environment that is not conducive to generating a sense of belonging may have an untoward impact on care delivery. Healthcare policies need to ensure patient care has a focus on engaging practitioners within multidisciplinary teams. © 2013 International Council of

Next-generation mTOR inhibitors in clinical oncology: how pathway complexity informs therapeutic strategy.

LENUS (Irish Health Repository)

Wander, Seth A

2011-04-01

Mammalian target of rapamycin (mTOR) is a PI3K-related kinase that regulates cell growth, proliferation, and survival via mTOR complex 1 (mTORC1) and mTORC2. The mTOR pathway is often aberrantly activated in cancers. While hypoxia, nutrient deprivation, and DNA damage restrain mTORC1 activity, multiple genetic events constitutively activate mTOR in cancers. Here we provide a brief overview of the signaling pathways up- and downstream of mTORC1 and -2, and discuss the insights into therapeutic anticancer targets - both those that have been tried in the clinic with limited success and those currently under clinical development - that knowledge of these pathways gives us.

Tomato FK506 Binding Protein 12KD (FKBP12 mediates the interaction between rapamycin and Target of Rapamycin (TOR

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Fangjie Xiong

2016-11-01

Full Text Available Target of Rapamycin (TOR signaling is an important regulator in multiple organisms including yeast, plants and animals. However, the TOR signaling in plants is much less understood as compared to that in yeast and animals. TOR kinase can be efficiently suppressed by rapamycin in the presence of functional FK506 Binding Protein 12KD (FKBP12 in yeast and animals. In most examined higher plants rapamycin fails to inhibit TOR kinase due to the non-functional FKBP12. Here we find that tomato plants showed obvious growth inhibition when treated with rapamycin and the inhibitory phenotype is similar to suppression of TOR causing by active-site TOR inhibitors (asTORis such as KU63794, AZD8055 and Torin1. The chemical genetic assays using TOR inhibitors and heterologous expressing SlFKBP12 in Arabidopsis indicated that the TOR signaling is functional in tomato. The protein gel shifting and TOR inhibitors combination assays showed that SlFKBP12 can mediate the interaction between rapamycin and TOR. Furthermore, comparative expression profiling analysis between treatments with rapamycin and KU63794 identified highly overlapped Differentially Expressed Genes (DEGs which are involved in many anabolic and catabolic processes, such as photosynthesis, cell wall restructuring, and senescence in tomato. These observations suggest that SlFFBP12 is functional in tomato. The results provided basic information of TOR signaling in tomato, and also some new insights into how TOR controls plant growth and development through reprogramming the transcription profiles

Tomato FK506 Binding Protein 12KD (FKBP12) Mediates the Interaction between Rapamycin and Target of Rapamycin (TOR).

Science.gov (United States)

Xiong, Fangjie; Dong, Pan; Liu, Mei; Xie, Gengxin; Wang, Kai; Zhuo, Fengping; Feng, Li; Yang, Lu; Li, Zhengguo; Ren, Maozhi

2016-01-01

Target of Rapamycin (TOR) signaling is an important regulator in multiple organisms including yeast, plants, and animals. However, the TOR signaling in plants is much less understood as compared to that in yeast and animals. TOR kinase can be efficiently suppressed by rapamycin in the presence of functional FK506 Binding Protein 12 KD (FKBP12) in yeast and animals. In most examined higher plants rapamycin fails to inhibit TOR kinase due to the non-functional FKBP12. Here we find that tomato plants showed obvious growth inhibition when treated with rapamycin and the inhibitory phenotype is similar to suppression of TOR causing by active-site TOR inhibitors (asTORis) such as KU63794, AZD8055, and Torin1. The chemical genetic assays using TOR inhibitors and heterologous expressing SlFKBP12 in Arabidopsis indicated that the TOR signaling is functional in tomato. The protein gel shifting and TOR inhibitors combination assays showed that SlFKBP12 can mediate the interaction between rapamycin and TOR. Furthermore, comparative expression profile analysis between treatments with rapamycin and KU63794 identified highly overlapped Differentially Expressed Genes (DEGs) which are involved in many anabolic and catabolic processes, such as photosynthesis, cell wall restructuring, and senescence in tomato. These observations suggest that SlFFBP12 is functional in tomato. The results provided basic information of TOR signaling in tomato, and also some new insights into how TOR controls plant growth and development through reprogramming the transcription profiles.

Adeno-Associated Viral Vector-Mediated mTOR Inhibition by Short Hairpin RNA Suppresses Laser-Induced Choroidal Neovascularization

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Tae Kwann Park

2017-09-01

Full Text Available Choroidal neovascularization (CNV is the defining characteristic feature of the wet subtype of age-related macular degeneration (AMD and may result in irreversible blindness. Based on anti-vascular endothelial growth factor (anti-VEGF, the current therapeutic approaches to CNV are fraught with difficulties, and mammalian target of rapamycin (mTOR has recently been proposed as a possible therapeutic target, although few studies have been conducted. Here, we show that a recombinant adeno-associated virus-delivered mTOR-inhibiting short hairpin RNA (rAAV-mTOR shRNA, which blocks the activity of both mTOR complex 1 and 2, represents a promising therapeutic approach for the treatment of CNV. Eight-week-old male C57/B6 mice were treated with the short hairpin RNA (shRNA after generating CNV lesions in the eyes via laser photocoagulation. The recombinant adeno-associated virus (rAAV delivery vehicle was able to effectively transduce cells in the inner retina, and significantly fewer inflammatory cells and less extensive CNV were observed in the animals treated with rAAV-mTOR shRNA when compared with control- and rAAV-scrambled shRNA-treated groups. Presumably related to the reduction of CNV, increased autophagy was detected in CNV lesions treated with rAAV-mTOR shRNA, whereas significantly fewer apoptotic cells detected in the outer nuclear layer around the CNV indicate that mTOR inhibition may also have neuroprotective effects. Taken together, these results demonstrate the therapeutic potential of mTOR inhibition, resulting from rAAV-mTOR shRNA activity, in the treatment of AMD-related CNV. Keywords: retinal neovascularization, choroidal neovascularization, adeno-associated virus, mTOR, RNA interference, mTOR shRNA, autophagy

Leadership in the Reform of Malaysian Universities: Analysing the Strategic Role of the Malaysian Qualifications Agency

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Bajunid, Ibrahim Ahmad

2011-01-01

This paper addresses the contemporary development and reform challenges in tertiary education in Malaysia in both national and global contexts. The critical role exercised by the Malaysian Qualifications Agency in driving strategic change in higher education cultures, both in public and private universities is described and analysed. The paper…

Anatomy learning styles and strategies among Jordanian and Malaysian medical students: the impact of culture on learning anatomy.

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Mustafa, Ayman G; Allouh, Mohammed Z; Mustafa, Intisar G; Hoja, Ibrahim M

2013-07-01

The study aims to investigate anatomy learning styles and strategies of Jordanian and Malaysian medical students at the Jordan University of Science and Technology. The study is a cross-sectional questionnaire-based study. Students' responses for the questionnaire were numerically coded, and the results were analyzed to reveal statistically significant differences between Jordanian and Malaysian students. The results showed that Jordanian medical students were less interested in using cadavers in learning anatomy than Malaysian medical students. However, similar to their Malaysian counterparts, they prefer to employ other tools to learn anatomy like plastinated models and Internet-based resources. In addition to the aforementioned tools, Malaysian students were more interested in using cross-sectional images and making their own revision cards. Both Jordanian and Malaysian medical students were more interested in learning anatomy through clinical cases, and by system rather than by region. Moreover, it was revealed that Jordanian medical students learn anatomy more efficiently when they formulate a general view of a particular topic. Both Jordanian and Malaysian medical students also relied on reciting definitions and memorizing facts to learn anatomy. The study also reported significant differences between Jordanian and Malaysian students' perspectives on learning anatomy. The findings of the study suggest that Jordanian and Malaysian medical students posses different cultures of learning. Jordanian anatomy instructors need to consider these different learning cultures when they prepare their instructional methods and teaching materials to fulfill the educational needs of their culturally diverse students.

The Idea of a University: Rethinking the Malaysian Context

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Chang Da Wan

2015-07-01

Full Text Available This article explores the idea of a university with a specific focus in the Malaysian context. We begin the article guided by these questions—“What is a university?” and “What are universities for?”—in examining the historical and conceptual development of universities. This is followed by asking a more specific question—“What are Malaysian universities for?”—in which we discussed the overarching roles of public and private universities in this developing country. Having examined the roles of public and private universities, and taken into context the complexity and challenges surrounding these important societal institutions, we discuss two “experimental” initiatives in Malaysia: the APEX University (Accelerated Program for Excellence focusing on sustainability and the “humanversity”. On the one hand, these initiatives are intended to prepare and transform Malaysian universities to address not only the needs of society today, but critically, of tomorrow. On the other hand, they have implications and contributions to frame our thinking about the future ideas of a university not only in Malaysia, but regionally and globally.

Differential TOR activation and cell proliferation in Arabidopsis root and shoot apexes.

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Li, Xiaojuan; Cai, Wenguo; Liu, Yanlin; Li, Hui; Fu, Liwen; Liu, Zengyu; Xu, Lin; Liu, Hongtao; Xu, Tongda; Xiong, Yan

2017-03-07

The developmental plasticity of plants relies on the remarkable ability of the meristems to integrate nutrient and energy availability with environmental signals. Meristems in root and shoot apexes share highly similar molecular players but are spatially separated by soil. Whether and how these two meristematic tissues have differential activation requirements for local nutrient, hormone, and environmental cues (e.g., light) remain enigmatic in photosynthetic plants. Here, we report that the activation of root and shoot apexes relies on distinct glucose and light signals. Glucose energy signaling is sufficient to activate target of rapamycin (TOR) kinase in root apexes. In contrast, both the glucose and light signals are required for TOR activation in shoot apexes. Strikingly, exogenously applied auxin is able to replace light to activate TOR in shoot apexes and promote true leaf development. A relatively low concentration of auxin in the shoot and high concentration of auxin in the root might be responsible for this distinctive light requirement in root and shoot apexes, because light is required to promote auxin biosynthesis in the shoot. Furthermore, we reveal that the small GTPase Rho-related protein 2 (ROP2) transduces light-auxin signal to activate TOR by direct interaction, which, in turn, promotes transcription factors E2Fa,b for activating cell cycle genes in shoot apexes. Consistently, constitutively activated ROP2 plants stimulate TOR in the shoot apex and cause true leaf development even without light. Together, our findings establish a pivotal hub role of TOR signaling in integrating different environmental signals to regulate distinct developmental transition and growth in the shoot and root.

Target of rapamycin (TOR) plays a critical role in triacylglycerol accumulation in microalgae.

Science.gov (United States)

Imamura, Sousuke; Kawase, Yasuko; Kobayashi, Ikki; Sone, Toshiyuki; Era, Atsuko; Miyagishima, Shin-Ya; Shimojima, Mie; Ohta, Hiroyuki; Tanaka, Kan

2015-10-01

Most microalgae produce triacylglycerol (TAG) under stress conditions such as nitrogen depletion, but the underlying molecular mechanism remains unclear. In this study, we focused on the role of target of rapamycin (TOR) in TAG accumulation. TOR is a serine/threonine protein kinase that is highly conserved and plays pivotal roles in nitrogen and other signaling pathways in eukaryotes. We previously constructed a rapamycin-susceptible Cyanidioschyzon merolae, a unicellular red alga, by expressing yeast FKBP12 protein to evaluate the results of TOR inhibition (Imamura et al. in Biochem Biophys Res Commun 439:264-269, 2013). By using this strain, we here report that rapamycin-induced TOR inhibition results in accumulation of cytoplasmic lipid droplets containing TAG. Transcripts for TAG synthesis-related genes, such as glycerol-3-phosphate acyltransferase and acyl-CoA:diacylglycerol acyltransferase (DGAT), were increased by rapamycin treatment. We also found that fatty acid synthase-dependent de novo fatty acid synthesis was required for the accumulation of lipid droplets. Induction of TAG and up-regulation of DGAT gene expression by rapamycin were similarly observed in the unicellular green alga, Chlamydomonas reinhardtii. These results suggest the general involvement of TOR signaling in TAG accumulation in divergent microalgae.

Effects of Focus of Accounting Research on the Quality of Accounting Education in Malaysian Universities

OpenAIRE

Kabiru Isa Dandago; Nor Azlina Binti Shaari

2013-01-01

This paper reviews the impact of focus of research in accounting on the quality of accounting education in Malaysian Universities. Research in accounting is very important in Malaysian Universities, in particular, and the Malaysian tertiary educational institutions, in general, and it is expected that academic research in accounting would improve the quality of accounting education in the country. The study is mainly a literature review type, with some informal interviews conducted for confir...

Heysham II/Torness AGR core integrity

International Nuclear Information System (INIS)

Birch, A.L.; Hampson, J.D.

1985-01-01

The design and construction process for the Heysham II/Torness AGR core structures is presented. The design intent utilizing all past experience in designing and building AGR core structures is described. The major aspects of the design criteria and the design conditions are outlined to demonstrate how the integrity of the Heysham II/Torness core is assured. Since no recognized codes of practice for graphite core design exist, the National Nuclear Corporation (NNC) have conceived design criteria utilizing reserve factors based on their design experience. Target reserve factors are defined for particular loading conditions including the ultimate 'safe-shutdown earthquake'. The substantial programme of computer analysis and RandD work to substantiate the design, including seismic qualification, is described. In keeping with their responsibility for the detailed core structure design and the fuel path geometry (guide tube system), NNC attach great importance to design/manufacture/construction liaison, which is demonstrated in the quality assurance section. (author)

Corporate governance and earnings quality : evidence from the Malaysian banking sector

OpenAIRE

Siniah, Thangamany

2017-01-01

This thesis investigates whether corporate governance conformance by Malaysian banks improves their financial reporting quality. It is motivated by the controversies surrounding corporate governance reforms and the calls for systematic research on its efficacy in the post-reform period. Malaysian banks have been subject to international standards of corporate governance since before and after the 1997–1998 Asian Financial Crisis. Malaysia’s common-law tradition, greater level of financial and...

PRELIMINARY REVISIONS OF SOME GENERA OF MALAYSIAN PAPILIONACEAE II

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MS van Meeuwen

2014-01-01

Full Text Available The revisions or notes have been prepared by Miss M. S. van Meeuwen, except for those of Pseudarthria and Sophora by C. G. G. J. van Steenis, and Tephrosia by J. Stemmerik. In Alysicarpus 4 species are distinguished in Malaysia; a key, synonymy, and discussion are given.Lourea Desv., being a homonym, has, according to Dr. Bakhuizen van den Brink, to be replaced by Christia; a key and discussion is given of 4 Malaysian species; 5 new combinations are proposed. Under Desmodium the variability of D. heterocarpon (L. DC. and its full synonymy are discussed; one new variety is proposed; an enumeration of specimens of both varieties is given. D. ormooarpoides DC. and D. zonatum Miq. are two sharply distinct species which have been confused in the past; a key, synonyms, discussion, and enumeration of specimens ;; j are provided. The discrimination of D. sequax Wall, and D. viegaphyllum Zoll. is discussed and their synonymy given; specimens have been enumerated. Distribution is given of D. scorpiurus (Sw. Desv. and D. tor-tuosum (Sw.   DC. Psoraleai is revised for Malaysia where 4 species are recorded and keyed out; a fifth species must remain dubious, as the type could not be traced in the Paris Herbarium. Of Pseudarthria only one species occurs in Malaysia; its synonymy and distribution is given.Sophora longipes Merr.; an endemic species from the Philippines, is recorded for Timor. Of Tephro&ia maculata M. & P., from Papua, the synonymy is given and specimens enumerated; T. brachystachys Laut. & K. Seh. is reduced. Notes and distribution are given of T. zollingeri Backer. For T. mollie . Val., a later homonym, the new name T. papuana is proposed.

Review on Malaysian Rail Transit Operation and Management System: Issues and Solution in Integration

Science.gov (United States)

Masirin, Mohd Idrus Mohd; Salin, Aminah Mohd; Zainorabidin, Adnan; Martin, David; Samsuddin, Norshakina

2017-08-01

In any context, operation and management of transportation systems are key issues which may affect both life quality and economic development. In large urban agglomerations, an efficient public transportation system may help abate the negative externalities of private car use such as congestion, air and noise pollution, accident and fuel consumption, without excessively penalizing user travel times or zone accessibility. Thus, this study is conducted to appraise the Malaysian rural rail transit operation and management system, which are considered important as there are many issues and solution in integration of the services that need to be tackled more conscientiously. The purpose of this paper is to describe some of the most important issues on integration of services and rail transit system in Malaysian and how to solve or reduce these problems and conflicts. In this paper, it consists of the historical development of rail transit construction in Malaysia. This paper also attempts to identify the important issues related to rail transit services and integration in Malaysian rural rail operation and management system. Comparison is also conducted with other countries such as UK, France, and Japan. Finally, a critical analysis is presented in this paper by looking at the possible application for future Malaysian rail transit operation system and management, especially focusing on enhancing the quality of Malaysian rural rail transit. In conclusion, this paper is expected to successfully review and appraise the existing Malaysian rural rail transit operation and management system pertaining to issues & solution in integration. It is also hoped that reformation or transformation of present service delivery quality of the rail transit operation and management will enable Malaysia to succeed in transforming Malaysian transportation system to greater heights.

Emotional Health and Self-esteem Among Adolescents in Malaysian Orphanages.

Science.gov (United States)

Mohammadzadeh, Marjan; Awang, Hamidin; Kadir Shahar, Hayati; Ismail, Suriani

2018-01-01

This study aimed to assess the prevalence and risk factors of depression, anxiety, stress and low self-esteem among institutional Malaysian adolescents. This cross-sectional descriptive study included 287 adolescents aged 12-18 years living in six selected orphan homes. Study's instruments included Socio-demographic questionnaire, validated Malay version of Depression Anxiety Stress Scale-21 and Rosenberg Self-Esteem Scale. The findings revealed that 85.2, 80.1 and 84.7% of participants had depression, anxiety and stress respectively. Females were more likely to be depressed. Furthermore, anxiety was significantly associated with race and age but no significant associations between stress and the demographic factors were found. The study also showed that 70.8% of males and 69.2% of females had low self-esteem and the self-esteem was associated with depression, anxiety and stress.Therefore, mental health problems are very common among adolescents in Malaysian orphanages. Results reveal the urgency of immediate actions to reduce the mental health problems among Malaysian institutional adolescents.

Inter-Religious Dialogue: The Perspective of Malaysian Contemporary Muslim Thinkers

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AEMY ELYANI MAT ZAIN

2014-06-01

Full Text Available Malaysia is a country that is rich for the diversity of its people. This diversity can be seen from the aspect of faith, ethnicity, language, culture, and so on. In facing a society that is pluralistic in nature, several initiatives have been taken by the government and non-government bodies in ensuring understanding and unity among Malaysians. Among the initiatives taken are interreligious dialogues. In this regard, many among Malaysian thinkers have proposed some approaches and concepts of inter-faith dialogue that should and may be implemented in the context of Malaysia. For that purpose, this paper examined the forms of inter-religious dialogues in Malaysia from the perspective of Malaysian contemporary Muslim thinkers. The methodology utilized in this study is textual analysis, particularly the writings of these thinkers on this issue. This article concludes that there are several forms of inter-religious dialogues that are easily implemented, as well as the difficult ones in the context of Malaysia due to certain obstacles.

Management of heatstroke in Malaysian pilgrims in Saudi Arabia.

Science.gov (United States)

Merican, M I

1989-09-01

Heat stroke is hardly seen in Malaysia. However, it occurs commonly in Saudi Arabia during the Haj season. Many Malaysian pilgrims are affected every year and some die. Having faced this environmental hazard for eight years, the Malaysian Medical Mission, sent each year to look after our pilgrims, modified its treatment strategy in 1988 and successfully decreased the overall morbidity and mortality of affected patients without the use of sophisticated equipment. A brief account of the management of 17 cases seen in 1988 is given. Only one died following treatment. The rest recovered fully without any residual neurological deficit or other complications.

TOR Signaling Promotes Accumulation of BZR1 to Balance Growth with Carbon Availability in Arabidopsis.

Science.gov (United States)

Zhang, Zhenzhen; Zhu, Jia-Ying; Roh, Jeehee; Marchive, Chloé; Kim, Seong-Ki; Meyer, Christian; Sun, Yu; Wang, Wenfei; Wang, Zhi-Yong

2016-07-25

For maintenance of cellular homeostasis, the actions of growth-promoting hormones must be attenuated when nutrient and energy become limiting. The molecular mechanisms that coordinate hormone-dependent growth responses with nutrient availability remain poorly understood in plants [1, 2]. The target of rapamycin (TOR) kinase is an evolutionarily conserved master regulator that integrates nutrient and energy signaling to regulate growth and homeostasis in both animals and plants [3-7]. Here, we show that sugar signaling through TOR controls the accumulation of the brassinosteroid (BR)-signaling transcription factor BZR1, which is essential for growth promotion by multiple hormonal and environmental signals [8-11]. Starvation, caused by shifting of light-grown Arabidopsis seedlings into darkness, as well as inhibition of TOR by inducible RNAi, led to plant growth arrest and reduced expression of BR-responsive genes. The growth arrest caused by TOR inactivation was partially recovered by BR treatment and the gain-of-function mutation bzr1-1D, which causes accumulation of active forms of BZR1 [12]. Exogenous sugar promoted BZR1 accumulation and seedling growth, but such sugar effects were largely abolished by inactivation of TOR, whereas the effect of TOR inactivation on BZR1 degradation is abolished by inhibition of autophagy and by the bzr1-1D mutation. These results indicate that cellular starvation leads sequentially to TOR inactivation, autophagy, and BZR1 degradation. Such regulation of BZR1 accumulation by glucose-TOR signaling allows carbon availability to control the growth promotion hormonal programs, ensuring supply-demand balance in plant growth. Copyright © 2016 Elsevier Ltd. All rights reserved.

PI3K-Akt signaling activates mTOR-mediated epileptogenesis in organotypic hippocampal culture model of posttraumatic epilepsy

Science.gov (United States)

Berdichevsky, Yevgeny; Dryer, Alexandra M.; Saponjian, Yero; Mahoney, Mark M.; Pimentel, Corrin A.; Lucini, Corrina A.; Usenovic, Marija; Staley, Kevin J.

2013-01-01

mTOR is activated in epilepsy, but the mechanisms of mTOR activation in post-traumatic epileptogenesis are unknown. It is also not clear whether mTOR inhibition has an antiepileptogenic, or merely anti-convulsive effect. The rat hippocampal organotypic culture model of post-traumatic epilepsy was used to study the effects of long term (four weeks) inhibition of signaling pathways that interact with mTOR. Ictal activity was quantified by measurement of lactate production and electrical recordings, and cell death was quantified with LDH release measurements and Nissl-stained neuron counts. Lactate and LDH measurements were well-correlated with electrographic activity and neuron counts, respectively. Inhibition of PI3K and Akt prevented activation of mTOR, and was as effective as inhibition of mTOR in reducing ictal activity and cell death. A dual inhibitor of PI3K and mTOR, NVP-BEZ235, was also effective. Inhibition of mTOR with rapamycin reduced axon sprouting. Late start of rapamycin treatment was effective in reducing epileptic activity and cell death, while early termination of rapamycin treatment did not result in increased epileptic activity or cell death. The conclusions of the study are: (1), the organotypic hippocampal culture model of posttraumatic epilepsy comprises a rapid assay of antiepileptogenic and neuroprotective activities and, in this model (2), mTOR activation depends on PI3K-Akt signaling, and (3) transient inhibition of mTOR has sustained effects on epilepsy. PMID:23699517

Are invertebrates relevant models in ageing research? Focus on the effects of rapamycin on TOR.

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Erdogan, Cihan Suleyman; Hansen, Benni Winding; Vang, Ole

2016-01-01

Ageing is the organisms increased susceptibility to death, which is linked to accumulated damage in the cells and tissues. Ageing is a complex process regulated by crosstalk of various pathways in the cells. Ageing is highly regulated by the Target of Rapamycin (TOR) pathway activity. TOR is an evolutionary conserved key protein kinase in the TOR pathway that regulates growth, proliferation and cell metabolism in response to nutrients, growth factors and stress. Comparing the ageing process in invertebrate model organisms with relatively short lifespan with mammals provides valuable information about the molecular mechanisms underlying the ageing process faster than mammal systems. Inhibition of the TOR pathway activity via either genetic manipulation or rapamycin increases lifespan profoundly in most invertebrate model organisms. This contribution will review the recent findings in invertebrates concerning the TOR pathway and effects of TOR inhibition by rapamycin on lifespan. Besides some contradictory results, the majority points out that rapamycin induces longevity. This suggests that administration of rapamycin in invertebrates is a promising tool for pursuing the scientific puzzle of lifespan prolongation. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Follistatin-mediated skeletal muscle hypertrophy is regulated by Smad3 and mTOR independently of myostatin

Science.gov (United States)

Winbanks, Catherine E.; Weeks, Kate L.; Thomson, Rachel E.; Sepulveda, Patricio V.; Beyer, Claudia; Qian, Hongwei; Chen, Justin L.; Allen, James M.; Lancaster, Graeme I.; Febbraio, Mark A.; Harrison, Craig A.; McMullen, Julie R.; Chamberlain, Jeffrey S.

2012-01-01

Follistatin is essential for skeletal muscle development and growth, but the intracellular signaling networks that regulate follistatin-mediated effects are not well defined. We show here that the administration of an adeno-associated viral vector expressing follistatin-288aa (rAAV6:Fst-288) markedly increased muscle mass and force-producing capacity concomitant with increased protein synthesis and mammalian target of rapamycin (mTOR) activation. These effects were attenuated by inhibition of mTOR or deletion of S6K1/2. Furthermore, we identify Smad3 as the critical intracellular link that mediates the effects of follistatin on mTOR signaling. Expression of constitutively active Smad3 not only markedly prevented skeletal muscle growth induced by follistatin but also potently suppressed follistatin-induced Akt/mTOR/S6K signaling. Importantly, the regulation of Smad3- and mTOR-dependent events by follistatin occurred independently of overexpression or knockout of myostatin, a key repressor of muscle development that can regulate Smad3 and mTOR signaling and that is itself inhibited by follistatin. These findings identify a critical role of Smad3/Akt/mTOR/S6K/S6RP signaling in follistatin-mediated muscle growth that operates independently of myostatin-driven mechanisms. PMID:22711699

Muslim refugees in Southeast Asia, the Malaysian response.

Science.gov (United States)

Dorall, R F

1988-01-01

This article surveys the arrivals of Muslim refugees from countries in Southeast Asia who have not only come to Malaysia for political refuge, but who have also stayed on, in many instances integrating into the local Muslim community. The author concludes that Burmese, Thai, and Filipino Muslim refugee-cum-migrants, and the estimated 500,000 illegal Indonesian migrant workers in East and Peninsular Malaysia make the presence of economic migrants in Malaysia's towns and rural sectors a far more pressing concern to Malaysians than that posed by the arrival of genuine political refugees. Only the Indonesians present in Malaysia are consistently termed by all parties as illegal migrants and some of them have been subjected to well-publicized deportation by the Malaysian immigration authorities. Sympathy for fellow-Muslims in distress explains Malaysia's open-door policy to Muslim refugees. The Koran specifically enjoins Muslims to assist Muslim refugees who have been persecuted by others. However, the necessity to maintain regional political and military alliances, principally as a bulwark against Communism, and the Malay--Non-Malay, Muslim--Non-Muslim dichotomy in Malaysia which almost evenly divides Malaysia's 16 million population into mutually antagonistic halves, results in any overt public policy in favor of Malays and Muslims to be immediately denounced by the other half of the population as a move against the Non-Malays and Non-Muslims. Without political and media attention, the refugees live wherever they can find work, as do hundreds of thousands of mainly Indonesian illegal migrant workers. They surreptitiously get their children admitted to public schools, and through bribery, can even get Malaysian identification papers. Malaysia is a relatively tranquil haven for Malaysia's Muslim refugees compared to their homelands, but their continued stay remains dependent on the ever-present struggle for more equitable sharing of political and economic power between

Intellectual capital disclosure and corporate governance structure among Malaysian government-linked companies

Directory of Open Access Journals (Sweden)

Rashidah Abdul Rahman

2013-11-01

Full Text Available This study examines the level of intellectual capital disclosure among the 32 Malaysian GLCs by comparing with the Non-GLCs for the period 2007-2009. In addition, this study also investigates the impact of board structure on the intellectual capital disclosure of Malaysian GLCs. The board structure mechanisms comprise; board composition, role duality, board size and cross directorship. The control variables consist of the company-specific characteristics –leverage, profitability and age of the company. The content analysis is used to extract the intellectual capital disclosure items from the annual report. The results show that the GLCs disclosed more intellectual capital information than Non-GLCs. Board size and leverage are significant and positively related to the intellectual capital disclosure of Malaysian GLCs.

Techniques of Teaching Arabic as a Foreign Language through Constructivist Paradigm: Malaysian Perspective

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Faryadi, Qais

2007-01-01

This analysis discusses the constructivist paradigm of teaching Arabic as a foreign language in Malaysian settings. This review examines the role of interactive multimedia in enhancing the chalk and talk methods of teaching Arabic in Malaysian schools. This paper also investigates the importance of Arabic Language in Malaysia. Furthermore, the…

Phenformin-Induced Mitochondrial Dysfunction Sensitizes Hepatocellular Carcinoma for Dual Inhibition of mTOR.

Science.gov (United States)

Veiga, Sonia Rosa; Ge, Xuemei; Mercer, Carol A; Hernández-Alvarez, María Isabel; Thomas, Hala Elnakat; Hernández-Losa, Javier; Ramón Y Cajal, Santiago; Zorzano, Antonio; Thomas, George; Kozma, Sara C

2018-04-24

Hepatocellular carcinoma (HCC) ranks second in cancer mortality and has limited therapeutic options. We recently described the synergistic effect of allosteric and ATP-site competitive inhibitors against the mammalian target of rapamycin (mTOR) for the treatment of HCC. However, such inhibitors induce glycemia and increase mitochondrial efficiency. Here we determined whether the mitochondrial complex I inhibitor Phenformin could reverse both side effects, impose an energetic-stress on cancer cells and suppress the growth of HCC. Human HCC cell lines were used in vitro to access the signaling and energetic impact of mTOR inhibitors and Phenformin, either alone or in combination. Next, the therapeutic utility of these drugs alone or in combination was investigated pre-clinically in human orthotopic tumors implanted in mice, by analyzing their impact on the tumor burden and overall survival. We found Phenformin caused mitochondrial dysfunction and fragmentation, inducing a compensatory shift to glycolysis. In contrast, dual inhibition of mTOR impaired cell growth and glycolysis, while increasing mitochondrial fusion and efficiency. In a mouse model of human HCC, dual inhibition of mTOR, together with Phenformin, was highly efficacious in controlling tumor burden. However, more striking, pretreatment with Phenformin sensitized tumors to dual inhibition of mTOR, leading to a dramatic improvement in survival. Treatment of HCC cells in vitro with the biguanide Phenformin causes a metabolic shift to glycolysis, mitochondrial dysfunction and fragmentation, and dramatically sensitizes orthotopic liver tumors to dual inhibition of mTOR. We therefore propose this therapeutic approach should be tested clinically in HCC. Copyright ©2018, American Association for Cancer Research.

Socioemotional Wealth and Firms’ Control: Evidence from Malaysian Chinese Owned Companies

OpenAIRE

Goh, Chin Fei; Rasli, Amran; Tan, Owee Kowang; Choi, Sang Long

2015-01-01

This paper explores how the preservation of socioemotional wealth can be manifested in the control and corporate governance of Malaysian Chinese firms. Using panel data from the Industrial Products index of the Bursa Malaysia (the Malaysian stock exchange) during 2003-2006, we show that the ingrained ‘life-raft values’ among overseas Chinese entrepreneurs can be associated with the preservation of their socioemotional wealth, and thus they prioritize control over their firms. Additionally, we...

Repositioning Strategy for Malaysian Companies Internationalization

Directory of Open Access Journals (Sweden)

Ismi Rajiani

2013-05-01

Full Text Available 1024x768 The rise of the emerging-market countries offers both developing and developed countries a unique opportunity to gain the benefits of a truly international economy. Consequently, it is imperative to advance our knowledge of emerging-market countries MNC emergence and competitiveness including Malaysian firms on how will they position their products strategically? Based on the framework of Porter’s Generic Strategy this paper is composed of price/ volume segments and impacts on product strategy theory. The aim is to identify crucial triggering cues and focus areas for Malaysian companies and measure what role these play in different segments. This study argues that some Malaysian companies will reposition themselves strategically when internationalizing and that they will focus on other factors or triggering cues when doing so not merely adapting the prevalent price leadership strategy. Normal 0 false false false IN X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;}

Finding a better drug for epilepsy: The mTOR pathway as an antiepileptogenic target

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Galanopoulou, Aristea S.; Gorter, Jan A.; Cepeda, Carlos

2012-01-01

Summary The mTOR signaling pathway regulates cell growth, differentiation, proliferation and metabolism. Loss of function mutations in upstream regulators of mTOR have been highly associated with dysplasias, epilepsy and neurodevelopmental disorders. These include tuberous sclerosis, which is due to mutations in TSC1 or TSC2 genes, mutations in phosphatase and tensin homolog (PTEN) as in Cowden syndrome, polyhydramnios, megalencephaly, symptomatic epilepsy syndrome (PMSE) due to mutations in the STE20-related kinase adaptor alpha (STRADalpha), and neurofibromatosis type 1 attributed to neurofibromin 1 mutations. Inhibition of the mTOR pathway with rapamycin may prevent epilepsy and improve the underlying pathology in mouse models with disrupted mTOR signaling, due to PTEN or TSC mutations. However the timing and duration of its administration appear critical in defining the seizure and pathology-related outcomes. Rapamycin application in human cortical slices from patients with cortical dysplasias reduces the 4-aminopyridine induced oscillations. In the multiple-hit model of infantile spasms, pulse high dose rapamycin administration can reduce the cortical overactivation of the mTOR pathway, suppresses spasms and has disease-modifying effects by partially improving cognitive deficits. In post-status epilepticus models of temporal lobe epilepsy, rapamycin may ameliorate the development of epilepsy-related pathology and reduce the expression of spontaneous seizures, but its effects depend on the timing and duration of administration, and possibly the model used. The observed recurrence of seizures and epilepsy-related pathology after rapamycin discontinuation suggests the need for continuous administration to maintain the benefit. However, the use of pulse administration protocols may be useful in certain age-specific epilepsy syndromes, like infantile spasms, whereas repetitive pulse rapamycin protocols may suffice to sustain a long-term benefit in genetic disorders

LAUGHING AT OURSELVES: REFLECTING MALAYSIAN ETHNIC DISPARITIES

Directory of Open Access Journals (Sweden)

SWAGATA SINHA ROY

2014-05-01

Full Text Available Malaysia’s various ethnic groups make interesting study both sociologically and culturally. With such a heady mix of cultural elements to explore, it is often natural that the many groups stumble upon ‘rare gems’ that reflect their ‘Malaysianess’. Have Malaysians really ever appreciated the many and varied aspects of culture that they are seemingly suddenly thrown into? Do we embrace these happily or are we constantly rejecting them? Fortunately, through the medium of film, we are, from time to time, allowed to reflect on our obvious similarities and even more apparent disparities. In this paper, we explore the culture and perceptions of people from the major ethnic groups that are the human base of this very country. When was it we have last laughed at ourselves … heartily? Nasi Lemak 2.0 provides an interesting, if not disturbing insight into the workings of the Malaysian ‘mind’. Nasi Lemak 2.0 was released on 8th September 2011 and impacted a whole generation of Malaysians. The characters have been well chosen and have done a wonderful job of being representations of the various communities in this nation. Ethnocentrism is a reality and often rears its head, ‘ugly’ or otherwise in several situations. Are we able to grapple with the levels of ethnocentrism that we encounter? These are some of the issues that will trigger much debate and discussion among ourselves and perhaps also reflect our cores.

Characterization of mTOR-Responsive Truncated mRNAs in Cell Proliferation

Science.gov (United States)

2017-07-01

These findings identify a previously uncharacterized role for mTOR in modulating 3’- UTR length of mRNAs by alternative polyadenylation ( APA ). Another...outcome of APA in the mTOR-activated transcriptome is an early termination of mRNA transcription to produce truncated mRNAs with polyadenylation in...for exhaustive analysis of Alternative cleavage and polyadenylation ( APA ) events (Figure 1). In IntMAP, first the position of multiple

Interaction between NBS1 and the mTOR/Rictor/SIN1 complex through specific domains.

Directory of Open Access Journals (Sweden)

Jian-Qiu Wang

Full Text Available Nijmegen breakage syndrome (NBS is a chromosomal-instability syndrome. The NBS gene product, NBS1 (p95 or nibrin, is a part of the Mre11-Rad50-NBS1 complex. SIN1 is a component of the mTOR/Rictor/SIN1 complex mediating the activation of Akt. Here we show that NBS1 interacted with mTOR, Rictor, and SIN1. The specific domains of mTOR, Rictor, or SIN1 interacted with the internal domain (a.a. 221-402 of NBS1. Sucrose density gradient showed that NBS1 was located in the same fractions as the mTOR/Rictor/SIN1 complex. Knockdown of NBS1 decreased the levels of phosphorylated Akt and its downstream targets. Ionizing radiation (IR increased the NBS1 levels and activated Akt activity. These results demonstrate that NBS1 interacts with the mTOR/Rictor/SIN1 complex through the a.a. 221-402 domain and contributes to the activation of Akt activity.

Reciprocal Regulation of the TOR Kinase and ABA Receptor Balances Plant Growth and Stress Response.

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Wang, Pengcheng; Zhao, Yang; Li, Zhongpeng; Hsu, Chuan-Chih; Liu, Xue; Fu, Liwen; Hou, Yueh-Ju; Du, Yanyan; Xie, Shaojun; Zhang, Chunguang; Gao, Jinghui; Cao, Minjie; Huang, Xiaosan; Zhu, Yingfang; Tang, Kai; Wang, Xingang; Tao, W Andy; Xiong, Yan; Zhu, Jian-Kang

2018-01-04

As sessile organisms, plants must adapt to variations in the environment. Environmental stress triggers various responses, including growth inhibition, mediated by the plant hormone abscisic acid (ABA). The mechanisms that integrate stress responses with growth are poorly understood. Here, we discovered that the Target of Rapamycin (TOR) kinase phosphorylates PYL ABA receptors at a conserved serine residue to prevent activation of the stress response in unstressed plants. This phosphorylation disrupts PYL association with ABA and with PP2C phosphatase effectors, leading to inactivation of SnRK2 kinases. Under stress, ABA-activated SnRK2s phosphorylate Raptor, a component of the TOR complex, triggering TOR complex dissociation and inhibition. Thus, TOR signaling represses ABA signaling and stress responses in unstressed conditions, whereas ABA signaling represses TOR signaling and growth during times of stress. Plants utilize this conserved phospho-regulatory feedback mechanism to optimize the balance of growth and stress responses. Copyright © 2017 Elsevier Inc. All rights reserved.

CXCR4/CXCL12/CXCR7 axis is functional in neuroendocrine tumors and signals on mTOR.

Science.gov (United States)

Circelli, Luisa; Sciammarella, Concetta; Guadagno, Elia; Tafuto, Salvatore; del Basso de Caro, Marialaura; Botti, Giovanni; Pezzullo, Luciano; Aria, Massimo; Ramundo, Valeria; Tatangelo, Fabiana; Losito, Nunzia Simona; Ieranò, Caterina; D'Alterio, Crescenzo; Izzo, Francesco; Ciliberto, Gennaro; Colao, Annamaria; Faggiano, Antongiulio; Scala, Stefania

2016-04-05

To evaluate the possible crosstalk between C-X-C chemokine receptor 4 (CXCR4)/C-X-C motif chemokine 12 (CXCL12)/C-X-C chemokine receptor 7 (CXCR7) axis with the mammalian target of rapamycin (mTOR) pathway in neuroendocrine tumors (NETs). Sixty-one human NETs were included into the study. CXCR4/CXCL12/CXCR7 axis and mTOR pathway were assessed by qRT-PCR and immunohistochemistry (IHC). The effect of mTOR inhibitor, RAD001, was evaluated on CXCR4 pathway through proliferation and p-Erk and p-AKT induction. CXCR4/CXCL12/CXCR7 axis and p-mTOR were found to be active and correlated with grading, Ki67 index and tumor stage. mTOR pathway activation significantly correlated with poor prognosis. In human NET cells, CXCL12 induced mTOR signalling while AMD3100 (CXCR4-antagonist) impaired it. The mTOR-antagonist, RAD001, impaired the CXCL12-dependent induction of CXCR4 downstream effectors. Combination of AMD3100 and RAD001 potentiate cell growth inhibition. CXCR4/CXCL12/CXCR7 axis is active in NETs and signals on mTOR. CXCR4 might be considered a prognostic factor in NETs. Combined treatment with AMD3100 and RAD001 may provide clinical benefits in NET patients with drug-resistant.

The crosstalk between Target of Rapamycin (TOR) and Jasmonic Acid (JA) signaling existing in Arabidopsis and cotton.

Science.gov (United States)

Song, Yun; Zhao, Ge; Zhang, Xueyan; Li, Linxuan; Xiong, Fangjie; Zhuo, Fengping; Zhang, Chaojun; Yang, Zuoren; Datla, Raju; Ren, Maozhi; Li, Fuguang

2017-04-04

Target of rapamycin (TOR) acts as an important regulator of cell growth, development and stress responses in most examined diploid eukaryotes. However, little is known about TOR in tetraploid species such as cotton. Here, we show that TORC1-S6K-RPS6, the major signaling components, are conserved and further expanded in cotton genome. Though the cotton seedlings are insensitive to rapamycin, AZD8055, the second-generation inhibitor of TOR, can significantly suppress the growth in cotton. Global transcriptome analysis revealed that genes associated with jasmonic acid (JA) biosynthesis and transduction were significantly altered in AZD8055 treated cotton seedlings, suggesting the potential crosstalk between TOR and JA signaling. Pharmacological and genetic approaches have been employed to get further insights into the molecular mechanism of the crosstalk between TOR and JA. Combination of AZD8055 with methyl jasmonate can synergistically inhibit cotton growth, and additionally JA levels were significantly increased when cotton seedlings were subjected to AZD8055. JA biosynthetic and signaling mutants including jar1, coi1-2 and myc2-2 displayed TOR inhibitor-resistant phenotypes, whereas COI1 overexpression transgenic lines and jaz10 exhibited sensitivity to AZD8055. Consistently, cotton JAZ can partially rescue TOR-suppressed phenotypes in Arabidopsis. These evidences revealed that the crosstalk between TOR and JA pathway operates in cotton and Arabidopsis.

Differential control of ageing and lifespan by isoforms and splice variants across the mTOR network.

Science.gov (United States)

Razquin Navas, Patricia; Thedieck, Kathrin

2017-07-15

Ageing can be defined as the gradual deterioration of physiological functions, increasing the incidence of age-related disorders and the probability of death. Therefore, the term ageing not only reflects the lifespan of an organism but also refers to progressive functional impairment and disease. The nutrient-sensing kinase mTOR (mammalian target of rapamycin) is a major determinant of ageing. mTOR promotes cell growth and controls central metabolic pathways including protein biosynthesis, autophagy and glucose and lipid homoeostasis. The concept that mTOR has a crucial role in ageing is supported by numerous reports on the lifespan-prolonging effects of the mTOR inhibitor rapamycin in invertebrate and vertebrate model organisms. Dietary restriction increases lifespan and delays ageing phenotypes as well and mTOR has been assigned a major role in this process. This may suggest a causal relationship between the lifespan of an organism and its metabolic phenotype. More than 25 years after mTOR's discovery, a wealth of metabolic and ageing-related effects have been reported. In this review, we cover the current view on the contribution of the different elements of the mTOR signalling network to lifespan and age-related metabolic impairment. We specifically focus on distinct roles of isoforms and splice variants across the mTOR network. The comprehensive analysis of mouse knockout studies targeting these variants does not support a tight correlation between lifespan prolongation and improved metabolic phenotypes and questions the strict causal relationship between them. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Problem-Solving Skills and Suicidal Ideation Among Malaysian College Students: the Mediating Role of Hopelessness.

Science.gov (United States)

Abdollahi, Abbas; Talib, Mansor Abu; Yaacob, Siti Nor; Ismail, Zanariah

2016-04-01

Recent evidence suggests that suicidal ideation has increased among Malaysian college students over the past two decades; therefore, it is essential to increase our knowledge concerning the etiology of suicidal ideation among Malaysian college students. This study was conducted to examine the relationships between problem-solving skills, hopelessness, and suicidal ideation among Malaysian college students. The participants included 500 undergraduate students from two Malaysian public universities who completed the self-report questionnaires. Structural equation modeling estimated that college students with poor problem-solving confidence, external personal control of emotion, and avoiding style were more likely to report suicidal ideation. Hopelessness partially mediated the relationship between problem-solving skills and suicidal ideation. These findings reinforce the importance of poor problem-solving skills and hopelessness as risk factors for suicidal ideation among college students.

Malaysian sign language dataset for automatic sign language ...

African Journals Online (AJOL)

Journal of Fundamental and Applied Sciences. Journal Home · ABOUT ... SL recognition system based on the Malaysian Sign Language (MSL). Implementation results are described. Keywords: sign language; pattern classification; database.

Phenolic acid composition and antioxidant properties of Malaysian honeys.

Science.gov (United States)

Khalil, M I; Alam, N; Moniruzzaman, M; Sulaiman, S A; Gan, S H

2011-08-01

The phenolic acid and flavonoid contents of Malaysian Tualang, Gelam, and Borneo tropical honeys were compared to those of Manuka honey. Ferric reducing/antioxidant power assay (FRAP) and the 1,1-diphenyl-2-picryl-hydrazyl (DPPH) radical-scavenging activities were also quantified. All honey extracts exhibited high phenolic contents (15.21 ± 0.51- 42.23 ± 0.64 mg/kg), flavonoid contents (11.52 ± 0.27- 25.31 ± 0.37 mg/kg), FRAP values (892.15 ± 4.97- 363.38 ± 10.57 μM Fe[II]/kg), and high IC₅₀ of DPPH radical-scavenging activities (5.24 ± 0.40- 17.51 ± 0.51 mg/mL). Total of 6 phenolic acids (gallic, syringic, benzoic, trans-cinnamic, p-coumaric, and caffeic acids) and 5 flavonoids (catechin, kaempferol, naringenin, luteolin, and apigenin) were identified. Among the Malaysian honey samples, Tualang honey had the highest contents of phenolics, and flavonoids, and DPPH radical-scavenging activities. We conclude that among Malaysian honey samples, Tualang honey is the richest in phenolic acids, and flavonoid compounds, which have strong free radical-scavenging activities. © 2011 Institute of Food Technologists®

PI3K/Akt/mTOR Intracellular Pathway and Breast Cancer: Factors, Mechanism and Regulation.

Science.gov (United States)

Sharma, Var Ruchi; Gupta, Girish Kumar; Sharma, A K; Batra, Navneet; Sharma, Daljit K; Joshi, Amit; Sharma, Anil K

2017-01-01

The most recurrent and considered second most frequent cause of cancer-related deaths worldwide in women is the breast cancer. The key to diagnosis is early prediction and a curable stage but still treatment remains a great clinical challenge. Origin of the Problem: A number of studies have been carried out for the treatment of breast cancer which includes the targeted therapies and increased survival rates in women. Essential PI3K/mTOR signaling pathway activation has been observed in most breast cancers. The cell growth and tumor development in such cases involve phosphoinositide 3 kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) complex intracellular pathway. Through preclinical and clinical trials, it has been observed that there are a number of other inhibitors of PI3K/Akt/mTOR pathway, which either alone or in combination with cytotoxic agents can be used for endocrine therapies. Structure and regulation/deregulation of mTOR provides a greater insight into the action mechanism. Also, through this review, one could easily scan first and second generation inhibitors for PI3K/Akt/mTOR pathway besides targeted therapies for breast cancer and the precise role of mTOR. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Motivating talents in Thai and Malaysian service firms

DEFF Research Database (Denmark)

Lehmann, Sanne

2009-01-01

Talent development in Thailand and Malaysian service firms has become a prioritized human resource management practice as these societies move toward knowledge-based economies. This paper discusses talent management in the social, organizational and managerial context of firms in Thailand...... and Malaysia, and argues that such structures often counterbalance investments made in talent development. The paper concludes that new human resource management practices do not produce a difference per se. It is the mindset and attitude of various managers that makes the difference. The learning...... for practitioners is that they need to adapt existing social and organizational structures to their new human resource management practices. The paper is based mainly on qualitative interviews with human resource managers from Thai and Malaysian service firms....

DEPTOR-related mTOR suppression is involved in metformin's anti-cancer action in human liver cancer cells

Energy Technology Data Exchange (ETDEWEB)

Obara, Akio; Fujita, Yoshihito; Abudukadier, Abulizi; Fukushima, Toru; Oguri, Yasuo; Ogura, Masahito; Harashima, Shin-ichi; Hosokawa, Masaya; Inagaki, Nobuya, E-mail: inagaki@metab.kuhp.kyoto-u.ac.jp

2015-05-15

Metformin, one of the most commonly used drugs for patients with type 2 diabetes, recently has received much attention regarding its anti-cancer action. It is thought that the suppression of mTOR signaling is involved in metformin's anti-cancer action. Although liver cancer is one of the most responsive types of cancer for reduction of incidence by metformin, the molecular mechanism of the suppression of mTOR in liver remains unknown. In this study, we investigated the mechanism of the suppressing effect of metformin on mTOR signaling and cell proliferation using human liver cancer cells. Metformin suppressed phosphorylation of p70-S6 kinase, and ribosome protein S6, downstream targets of mTOR, and suppressed cell proliferation. We found that DEPTOR, an endogenous substrate of mTOR suppression, is involved in the suppressing effect of metformin on mTOR signaling and cell proliferation in human liver cancer cells. Metformin increases the protein levels of DEPTOR, intensifies binding to mTOR, and exerts a suppressing effect on mTOR signaling. This increasing effect of DEPTOR by metformin is regulated by the proteasome degradation system; the suppressing effect of metformin on mTOR signaling and cell proliferation is in a DEPTOR-dependent manner. Furthermore, metformin exerts a suppressing effect on proteasome activity, DEPTOR-related mTOR signaling, and cell proliferation in an AMPK-dependent manner. We conclude that DEPTOR-related mTOR suppression is involved in metformin's anti-cancer action in liver, and could be a novel target for anti-cancer therapy. - Highlights: • We elucidated a novel pathway of metformin's anti-cancer action in HCC cells. • DEPTOR is involved in the suppressing effect of metformin on mTOR signaling. • Metformin increases DEPTOR protein levels via suppression of proteasome activity. • DEPTOR-related mTOR suppression is involved in metformin's anti-cancer action.

DEPTOR-related mTOR suppression is involved in metformin's anti-cancer action in human liver cancer cells

International Nuclear Information System (INIS)

Obara, Akio; Fujita, Yoshihito; Abudukadier, Abulizi; Fukushima, Toru; Oguri, Yasuo; Ogura, Masahito; Harashima, Shin-ichi; Hosokawa, Masaya; Inagaki, Nobuya

2015-01-01

Metformin, one of the most commonly used drugs for patients with type 2 diabetes, recently has received much attention regarding its anti-cancer action. It is thought that the suppression of mTOR signaling is involved in metformin's anti-cancer action. Although liver cancer is one of the most responsive types of cancer for reduction of incidence by metformin, the molecular mechanism of the suppression of mTOR in liver remains unknown. In this study, we investigated the mechanism of the suppressing effect of metformin on mTOR signaling and cell proliferation using human liver cancer cells. Metformin suppressed phosphorylation of p70-S6 kinase, and ribosome protein S6, downstream targets of mTOR, and suppressed cell proliferation. We found that DEPTOR, an endogenous substrate of mTOR suppression, is involved in the suppressing effect of metformin on mTOR signaling and cell proliferation in human liver cancer cells. Metformin increases the protein levels of DEPTOR, intensifies binding to mTOR, and exerts a suppressing effect on mTOR signaling. This increasing effect of DEPTOR by metformin is regulated by the proteasome degradation system; the suppressing effect of metformin on mTOR signaling and cell proliferation is in a DEPTOR-dependent manner. Furthermore, metformin exerts a suppressing effect on proteasome activity, DEPTOR-related mTOR signaling, and cell proliferation in an AMPK-dependent manner. We conclude that DEPTOR-related mTOR suppression is involved in metformin's anti-cancer action in liver, and could be a novel target for anti-cancer therapy. - Highlights: • We elucidated a novel pathway of metformin's anti-cancer action in HCC cells. • DEPTOR is involved in the suppressing effect of metformin on mTOR signaling. • Metformin increases DEPTOR protein levels via suppression of proteasome activity. • DEPTOR-related mTOR suppression is involved in metformin's anti-cancer action

Predicting ambient aerosol Thermal Optical Reflectance (TOR) measurements from infrared spectra: elemental carbon

Science.gov (United States)

Dillner, A. M.; Takahama, S.

2015-06-01

Elemental carbon (EC) is an important constituent of atmospheric particulate matter because it absorbs solar radiation influencing climate and visibility and it adversely affects human health. The EC measured by thermal methods such as Thermal-Optical Reflectance (TOR) is operationally defined as the carbon that volatilizes from quartz filter samples at elevated temperatures in the presence of oxygen. Here, methods are presented to accurately predict TOR EC using Fourier Transform Infrared (FT-IR) absorbance spectra from atmospheric particulate matter collected on polytetrafluoroethylene (PTFE or Teflon) filters. This method is similar to the procedure tested and developed for OC in prior work (Dillner and Takahama, 2015). Transmittance FT-IR analysis is rapid, inexpensive, and non-destructive to the PTFE filter samples which are routinely collected for mass and elemental analysis in monitoring networks. FT-IR absorbance spectra are obtained from 794 filter samples from seven Interagency Monitoring of PROtected Visual Environment (IMPROVE) sites collected during 2011. Partial least squares regression is used to calibrate sample FT-IR absorbance spectra to collocated TOR EC measurements. The FTIR spectra are divided into calibration and test sets. Two calibrations are developed, one which is developed from uniform distribution of samples across the EC mass range (Uniform EC) and one developed from a~uniform distribution of low EC mass samples (EC < 2.4 μg, Low Uniform EC). A hybrid approach which applies the low EC calibration to low EC samples and the Uniform EC calibration to all other samples is used to produces predictions for low EC samples that have mean error on par with parallel TOR EC samples in the same mass range and an estimate of the minimum detection limit (MDL) that is on par with TOR EC MDL. For all samples, this hybrid approach leads to precise and accurate TOR EC predictions by FT-IR as indicated by high coefficient of variation (R2; 0.96), no

The Atg1-Tor pathway regulates yolk catabolism in Drosophila embryos.

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Kuhn, Hallie; Sopko, Richelle; Coughlin, Margaret; Perrimon, Norbert; Mitchison, Tim

2015-11-15

Yolk provides an important source of nutrients during the early development of oviparous organisms. It is composed mainly of vitellogenin proteins packed into membrane-bound compartments called yolk platelets. Catabolism of yolk is initiated by acidification of the yolk platelet, leading to the activation of Cathepsin-like proteinases, but it is unknown how this process is triggered. Yolk catabolism initiates at cellularization in Drosophila melanogaster embryos. Using maternal shRNA technology we found that yolk catabolism depends on the Tor pathway and on the autophagy-initiating kinase Atg1. Whereas Atg1 was required for a burst of spatially regulated autophagy during late cellularization, autophagy was not required for initiating yolk catabolism. We propose that the conserved Tor metabolic sensing pathway regulates yolk catabolism, similar to Tor-dependent metabolic regulation on the lysosome. © 2015. Published by The Company of Biologists Ltd.

CREDIT CONTROL MANAGEMENT AND BUSINESS PERFORMANCE : THE MALAYSIAN FAMILY SME PERSPECTIVE

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Edward Wong Sek Khin

2015-04-01

Full Text Available This study examined the relationship between control management and family business performance in the Malaysian context. It has two objectives, the first being to determine the relationship of organizational credit control policy and procedures, employee development and motivation, and intelligence collection systems to subsequent collection reports in Malaysian family SMEs. The second objective is to investigate the moderating effect of participation in decision-making and work effort towards innovation and business performance. This is a descriptive study involving 90 senior executives employed in 90 Malaysian family SMEs/firms. A correlation analysis from this study confirmed previous researchers' observations that high-level organizational commitment to credit control management is linked to improvements in business performance. The results suggest that three components - credit policy, employee development, and intelligence collection systems - are the most important predictors for the efficiency and effectiveness of credit control management.

Distribution of Depositors’ Return and The Income Smoothing Hypothesis by Malaysian Islamic Banks

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Zunaidah Sulong

2018-01-01

Full Text Available The paper aims to examine whether Malaysian Islamic banks carry out income smoothing with regards to their distribution of depositors’ return. The paper also examines the extent Malaysian Islamic banks engage earnings and capital management in their distribution of depositors’ return. This empirical study uses balanced panel data from 16 Malaysian Islamic banks, for the period 2008-2012. The regression model is estimated using random effects specifications. The findings indicate that the earnings before tax, zakat, and provision have a positive but insignificant effect on distribution of depositors’ return (DDR whilst the total capital before provision has a positive and significant effect on the DDR. These findings suggest that Islamic banks carry out income smoothing on the distribution of depositors’ return via capital management. Islamic banks also smooth their earnings through distribution of depositors’ return to avoid earnings troughs when earnings are poor. The findings shows prudence exercise among Malaysian Islamic banks with the objectives of mitigating displaced commercial risk (DCR, which involves massive withdrawal and bank runs risks.

Dual PI3K/mTOR inhibitor BEZ235 as a promising therapeutic strategy against paclitaxel-resistant gastric cancer via targeting PI3K/Akt/mTOR pathway.

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Chen, Dongshao; Lin, Xiaoting; Zhang, Cheng; Liu, Zhentao; Chen, Zuhua; Li, Zhongwu; Wang, Jingyuan; Li, Beifang; Hu, Yanting; Dong, Bin; Shen, Lin; Ji, Jiafu; Gao, Jing; Zhang, Xiaotian

2018-01-26

Paclitaxel (PTX) is widely used in the front-line chemotherapy for gastric cancer (GC), but resistance limits its use. Due to the lack of proper models, mechanisms underlying PTX resistance in GC were not well studied. Using established PTX-resistant GC cell sublines HGC-27R, we for the first time integrated biological traits and molecular mechanisms of PTX resistance in GC. Data revealed that PTX-resistant GC cells were characterized by microtubular disorders, an EMT phenotype, reduced responses to antimitotic drugs, and resistance to apoptosis (marked by upregulated β-tubulin III, vimentin, attenuated changes in G 2 /M molecules or pro-apoptotic factors in response to antimitotic drugs or apoptotic inducers, respectively). Activation of the phosphoinositide 3-kinase, the serine/threonine kinase Akt and mammalian target of rapamycin (PI3K/Akt/mTOR) and mitogen-activated protein kinase (MAPK) pathways were also observed, which might be the reason for above phenotypic alternations. In vitro data suggested that targeting these pathways were sufficient to elicit antitumor responses in PTX-resistant GC, in which the dual PI3K/mTOR inhibitor BEZ235 displayed higher therapeutic efficiency than the mTOR inhibitor everolimus or the MEK inhibitor AZD6244. Antitumor effects of BEZ235 were also confirmed in mice bearing HGC-27R tumors. Thus, these data suggest that PI3K/Akt/mTOR and MAPK pathway inhibition, especially PI3K/mTOR dual blockade, might be a promising therapeutic strategy against PTX-resistant GC.

PI3K-Akt signaling activates mTOR-mediated epileptogenesis in organotypic hippocampal culture model of post-traumatic epilepsy.

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Berdichevsky, Yevgeny; Dryer, Alexandra M; Saponjian, Yero; Mahoney, Mark M; Pimentel, Corrin A; Lucini, Corrina A; Usenovic, Marija; Staley, Kevin J

2013-05-22

mTOR is activated in epilepsy, but the mechanisms of mTOR activation in post-traumatic epileptogenesis are unknown. It is also not clear whether mTOR inhibition has an anti-epileptogenic, or merely anticonvulsive effect. The rat hippocampal organotypic culture model of post-traumatic epilepsy was used to study the effects of long-term (four weeks) inhibition of signaling pathways that interact with mTOR. Ictal activity was quantified by measurement of lactate production and electrical recordings, and cell death was quantified with lactate dehydrogenase (LDH) release measurements and Nissl-stained neuron counts. Lactate and LDH measurements were well correlated with electrographic activity and neuron counts, respectively. Inhibition of PI3K and Akt prevented activation of mTOR, and was as effective as inhibition of mTOR in reducing ictal activity and cell death. A dual inhibitor of PI3K and mTOR, NVP-BEZ235, was also effective. Inhibition of mTOR with rapamycin reduced axon sprouting. Late start of rapamycin treatment was effective in reducing epileptic activity and cell death, while early termination of rapamycin treatment did not result in increased epileptic activity or cell death. The conclusions of the study are as follows: (1) the organotypic hippocampal culture model of post-traumatic epilepsy comprises a rapid assay of anti-epileptogenic and neuroprotective activities and, in this model (2) mTOR activation depends on PI3K-Akt signaling, and (3) transient inhibition of mTOR has sustained effects on epilepsy.

Malaysian Children's Attitudes towards Learning Music

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Ghazali, Ghaziah Mohd.; McPherson, Gary E.

2009-01-01

A sample of 1060 Malaysian children were surveyed in order to examine differences in their motivation to study music in school and to learn a musical instrument outside of school. Adopting the expectancy-value motivation theory, the children were asked questions concerning their perception of music as being important, useful, interesting,…

Lessons from the Bone Chapter of the Malaysian Aging Men Study

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Kok-Yong Chin

2016-05-01

Full Text Available Male osteoporosis in Malaysia is a largely neglected problem. Therefore, a bone health study in men using quantitative ultrasonometry was launched as part of the Malaysian Aging Men Study in 2009–2012. This review aimed to summarize the findings of the aforementioned bone health study. The study examined the bone health of Chinese and Malaysian men aged 20 years and above living in Kuala Lumpur using a quantitative ultrasound device. Participants answered a questionnaire on their demographic details and physical activity status. Body anthropometry of the participants was measured and their blood collected for biochemical analysis. Results showed that a significant proportion of the Malaysian Chinese and Malay men had suboptimal bone health indicated by calcaneal speed of sound and vitamin D status. Age-related decline of the calcaneal speed of sound in these men was gradual and biphasic without ethnic difference. Body anthropometry such as height, weight, body mass index, and body fat percentage contributed to the variation of the calcaneal speed of sound in Malaysian men. Age-related changes in testosterone, insulin-like growth factor 1, and thyroid stimulating hormone also influenced the calcaneal speed of sound in these men. This study serves as a reminder that male osteoporosis in Malaysia should be an issue of concern. It is also a basis for a more comprehensive study on bone health in men in the future.

Lessons from the Bone Chapter of the Malaysian Aging Men Study.

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Chin, Kok-Yong; Wan Ngah, Wan Zurinah; Ima-Nirwana, Soelaiman

2016-05-25

Male osteoporosis in Malaysia is a largely neglected problem. Therefore, a bone health study in men using quantitative ultrasonometry was launched as part of the Malaysian Aging Men Study in 2009-2012. This review aimed to summarize the findings of the aforementioned bone health study. The study examined the bone health of Chinese and Malaysian men aged 20 years and above living in Kuala Lumpur using a quantitative ultrasound device. Participants answered a questionnaire on their demographic details and physical activity status. Body anthropometry of the participants was measured and their blood collected for biochemical analysis. Results showed that a significant proportion of the Malaysian Chinese and Malay men had suboptimal bone health indicated by calcaneal speed of sound and vitamin D status. Age-related decline of the calcaneal speed of sound in these men was gradual and biphasic without ethnic difference. Body anthropometry such as height, weight, body mass index, and body fat percentage contributed to the variation of the calcaneal speed of sound in Malaysian men. Age-related changes in testosterone, insulin-like growth factor 1, and thyroid stimulating hormone also influenced the calcaneal speed of sound in these men. This study serves as a reminder that male osteoporosis in Malaysia should be an issue of concern. It is also a basis for a more comprehensive study on bone health in men in the future.

Finding a better drug for epilepsy: the mTOR pathway as an antiepileptogenic target.

NARCIS (Netherlands)

Galanopoulou, A.S.; Gorter, J.A.; Cepeda, C.

2012-01-01

The mammalian target of rapamycin (mTOR) signaling pathway regulates cell growth, differentiation, proliferation, and metabolism. Loss-of-function mutations in upstream regulators of mTOR have been highly associated with dysplasias, epilepsy, and neurodevelopmental disorders. These include tuberous

Suprimento arterial do lobo torácico do timo em suínos da linhagem "Rezende"

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Gonçalez Patrícia Orlandini

2003-01-01

Full Text Available Foram dissecados 30 exemplares de fetos de suínos da linhagem "Rezende", após injeção do sistema vascular arterial, via artéria aorta descendente torácica, com Neoprene látex "450" corado com pigmento específico e fixação em solução aquosa de formol a 10%, para a observação da origem, número e ordenação das artérias destinadas ao lobo torácico do timo. O antímero esquerdo foi irrigado por ramos diretos das artérias torácica interna esquerda (96,66%, cervical superficial esquerda (40,00%, torácica interna direita (26,66%, tronco braquiocefálico (20,00%, subclávia esquerda (10,00%, carótida comum esquerda (10,00%, vertebral esquerda (6,66%, cervical superficial direita (6,66%, tronco bicarotídico (6,66%, torácica externa direita (3,33% e axilar esquerda (3,33%; ramos indiretos foram provenientes das artérias torácica interna esquerda (40,00%, cervical superficial esquerda (23,33% e subclávia esquerda (3,33%. O antímero direito foi irrigado por ramos diretos, provenientes das artérias torácica interna direita (63,33%, cervical superficial direita (13,33%, carótida comum direita (6,66%, torácica externa direita (3,33% e subclávia direita (3,33%; ramos indiretos foram originários das artérias torácica interna direita (20,00%, cervical superficial direita (10,00%, torácica externa direita (3,33% e subclávia direita (3,33%. A massa tímica do antímero direito esteve presente em 43,33% dos casos, ausente em 30,00% e reduzida em 26,66%, sendo observado de 1 a 7 ramos penetrantes em seu parênquima. A massa tímica do antímero esquerdo foi encontrada em 100,00% das dissecações, recebendo de 2 a 9 ramos penetrantes.

Vector competence of Malaysian Aedes albopictus with and without Wolbachia to four dengue virus serotypes.

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Joanne, Sylvia; Vythilingam, Indra; Teoh, Boon-Teong; Leong, Cherng-Shii; Tan, Kim-Kee; Wong, Meng-Li; Yugavathy, Nava; AbuBakar, Sazaly

2017-09-01

To determine the susceptibility status of Aedes albopictus with and without Wolbachia to the four dengue virus serotypes. Two newly colonised colonies of Ae. albopictus from the wild were used for the study. One colony was naturally infected with Wolbachia while in the other Wolbachia was removed by tetracycline treatment. Both colonies were orally infected with dengue virus-infected fresh blood meal. Dengue virus load was measured using quantitative RT-PCR at four-time intervals in the salivary glands, midguts and ovaries. Wolbachia did not significantly affect Malaysian Ae. albopictus dengue infection or the dissemination rate for all four dengue virus serotypes. Malaysian Ae. albopictus had the highest replication kinetics for DENV-1 and the highest salivary gland and midgut infection rate for DENV-4. Wolbachia, which naturally exists in Malaysian Ae. albopictus, does not significantly affect dengue virus replication. Malaysian Ae. albopictus is susceptible to dengue virus infections and capable of transmitting dengue virus, especially DENV-1 and DENV-4. Removal of Wolbachia from Malaysian Ae. albopictus would not reduce their susceptibility status. © 2017 John Wiley & Sons Ltd.

El Tor hemolysin of Vibrio cholerae O1 forms channels in planar lipid bilayer membranes.

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Ikigai, H; Ono, T; Iwata, M; Nakae, T; Shimamura, T

1997-05-15

We investigated the channel formation by El Tor hemolysin (molecular mass, 65 kDa) of Vibrio cholerae O1 biotype El Tor in planar lipid bilayers. The El Tor hemolysin channel exhibited asymmetric and hyperbolic membrane current with increasing membrane potential, meaning that the channel is voltage dependent. The zero-current membrane potential measured in KCI solution showed that permeability ratio PK+/PCl- was 0.16, indicating that the channel is 6-fold more anion selective over cation. The hemolysin channel frequently flickered in the presence of divalent cations, suggesting that the channel spontaneously opens and closes. These data imply that the El Tor hemolysin damages target cells by the formation of transmembrane channels and, consequently, is the cause of osmotic cytolysis.

TOR Pathway-Mediated Juvenile Hormone Synthesis Regulates Nutrient-Dependent Female Reproduction in Nilaparvata lugens (Stål).

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Lu, Kai; Chen, Xia; Liu, Wen-Ting; Zhou, Qiang

2016-03-28

The "target of rapamycin" (TOR) nutritional signaling pathway and juvenile hormone (JH) regulation of vitellogenesis has been known for a long time. However, the interplay between these two pathways regulating vitellogenin (Vg) expression remains obscure. Here, we first demonstrated the key role of amino acids (AAs) in activation of Vg synthesis and egg development in Nilaparvata lugens using chemically defined artificial diets. AAs induced the expression of TOR and S6K (S6 kinase), whereas RNAi-mediated silencing of these two TOR pathway genes and rapamycin application strongly inhibited the AAs-induced Vg synthesis. Furthermore, knockdown of Rheb (Ras homologue enriched in brain), TOR, S6K and application of rapamycin resulted in a dramatic reduction in the mRNA levels of jmtN (juvenile hormone acid methyltransferase, JHAMT). Application of JH III on the RNAi (Rheb and TOR) and rapamycin-treated females partially rescued the Vg expression. Conversely, knockdown of either jmtN or met (methoprene-tolerant, JH receptor) and application of JH III had no effects on mRNA levels of Rheb, TOR and S6K and phosphorylation of S6K. In summary, our results demonstrate that the TOR pathway induces JH biosynthesis that in turn regulates AAs-mediated Vg synthesis in N. lugens.

GIS in the analysis of the rhizomatic urban development of Tor Vergata

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Luisa Carbone

2013-06-01

Full Text Available The scope of this article is to observe the complexity of the relations between Rome’s University Campus of Tor Vergata and its discursive universe, from the former abusive districts to the re-qualified images of the suburbs of the 8th City Hall, raised to the rank of Centralities in the New Regulatory Plan of Rome. In order to understand the size of Tor Vergata’s system of relations, it is essential to use the application of the rhizomatic and virtual method of the performative mapping. A process involving the attribution of new meaning and a different order to what is already existing. In this context, only the potential of GIS can guide in de-codifying the territorial configuration of Tor Vergata, which finds in the rhizome, in the multiplicity of viewpoints and in the difference, the fundamental principle of its action. The rhizomatic view of the GIS, in fact, gives an innovative image by replacing the idea of insecurity with the idea of a structure which is not shapeless, and which represents Tor Vergata as a “place”, not anymore as a periphery.

Gender-dependent association of a β(2)-adrenergic gene variant with obesity parameters in Malaysian Malays.

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Apalasamy, Yamunah Devi; Ming, Moy Foong; Rampal, Sanjay; Bulgiba, Awang; Mohamed, Zahurin

2015-03-01

Recent findings have shown that the rs1042714 (Gln27Glu) single-nucleotide polymorphism (SNP) on the β2-adrenoceptor gene may predispose to obesity. The findings from other studies carried on different populations, however, have been inconsistent. The authors investigated the association between the rs1042714 SNP with obesity-related parameters. DNA of 672 Malaysian Malays was analyzed using real-time polymerase chain reaction. Univariate and multivariate linear regression analyses revealed significant associations between rs1042714 and diastolic blood pressure in the pooled Malaysian Malay subjects under additive and recessive models. After gender stratification, however, a significant association was found between the rs1042714 and triglyceride and the rs1042714 and log-transformed high-density lipoprotein cholesterol levels in Malaysian Malay men. No significant association was found between the SNP and log-transformed body mass index. This polymorphism may have an important role in the development of obesity-related traits in Malaysian Malays. Gender is an effect modifier for the effect of the rs1042714 polymorphism on obesity-related traits in Malaysian Malays. © 2011 APJPH.

PI3K-Akt signaling activates mTOR-mediated epileptogenesis in organotypic hippocampal culture model of posttraumatic epilepsy

OpenAIRE

Berdichevsky, Yevgeny; Dryer, Alexandra M.; Saponjian, Yero; Mahoney, Mark M.; Pimentel, Corrin A.; Lucini, Corrina A.; Usenovic, Marija; Staley, Kevin J.

2013-01-01

mTOR is activated in epilepsy, but the mechanisms of mTOR activation in post-traumatic epileptogenesis are unknown. It is also not clear whether mTOR inhibition has an antiepileptogenic, or merely anti-convulsive effect. The rat hippocampal organotypic culture model of post-traumatic epilepsy was used to study the effects of long term (four weeks) inhibition of signaling pathways that interact with mTOR. Ictal activity was quantified by measurement of lactate production and electrical recordi...

The TOR signaling pathway regulates vegetative development and virulence in Fusarium graminearum.

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Yu, Fangwei; Gu, Qin; Yun, Yingzi; Yin, Yanni; Xu, Jin-Rong; Shim, Won-Bo; Ma, Zhonghua

2014-07-01

The target of rapamycin (TOR) signaling pathway plays critical roles in controlling cell growth in a variety of eukaryotes. However, the contribution of this pathway in regulating virulence of plant pathogenic fungi is unknown. We identified and characterized nine genes encoding components of the TOR pathway in Fusarium graminearum. Biological, genetic and biochemical functions of each component were investigated. The FgFkbp12-rapamycin complex binds to the FgTor kinase. The type 2A phosphatases FgPp2A, FgSit4 and FgPpg1 were found to interact with FgTap42, a downstream component of FgTor. Among these, we determined that FgPp2A is likely to be essential for F. graminearum survival, and FgSit4 and FgPpg1 play important roles in cell wall integrity by positively regulating the phosphorylation of FgMgv1, a key MAP kinase in the cell wall integrity pathway. In addition, the FgPpg1 interacting protein, FgTip41, is involved in regulating mycelial growth and virulence. Notably, FgTip41 does not interact with FgTap42 but with FgPpg1, suggesting the existence of FgTap42:FgPpg1:FgTip41 heterotrimer in F. graminearum, a complex not observed in the yeast model. Collectively, we defined a genetic regulatory framework that elucidates how the TOR pathway regulates virulence and vegetative development in F. graminearum. © 2014 The Authors. New Phytologist © 2014 New Phytologist Trust.

Ribosomal protein S6 kinase1 coordinates with TOR-Raptor2 to regulate thylakoid membrane biosynthesis in rice.

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Sun, Linxiao; Yu, Yonghua; Hu, Weiqin; Min, Qiming; Kang, Huiling; Li, Yilu; Hong, Yue; Wang, Xuemin; Hong, Yueyun

2016-07-01

Ribosomal protein S6 kinase (S6K) functions as a key component in the target of rapamycin (TOR) pathway involved in multiple processes in eukaryotes. The role and regulation of TOR-S6K in lipid metabolism remained unknown in plants. Here we provide genetic and pharmacological evidence that TOR-Raptor2-S6K1 is important for thylakoid galactolipid biosynthesis and thylakoid grana modeling in rice (Oryza sativa L.). Genetic suppression of S6K1 caused pale yellow-green leaves, defective thylakoid grana architecture. S6K1 directly interacts with Raptor2, a core component in TOR signaling, and S6K1 activity is regulated by Raptor2 and TOR. Plants with suppressed Raptor2 expression or reduced TOR activity by inhibitors mimicked the S6K1-deficient phenotype. A significant reduction in galactolipid content was found in the s6k1, raptor2 mutant or TOR-inhibited plants, which was accompanied by decreased transcript levels of the set of genes such as lipid phosphate phosphatase α5 (LPPα5), MGDG synthase 1 (MGD1), and DGDG synthase 1 (DGD1) involved in galactolipid synthesis, compared to the control plants. Moreover, loss of LPPα5 exhibited a similar phenotype with pale yellow-green leaves. These results suggest that TOR-Raptor2-S6K1 is important for modulating thylakoid membrane lipid biosynthesis, homeostasis, thus enhancing thylakoid grana architecture and normal photosynthesis ability in rice. Copyright © 2016 Elsevier B.V. All rights reserved.

Malaysian University Students’ Attitudes towards Six Varieties of Accented Speech in English

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Zainab Thamer Ahmed

2014-10-01

Full Text Available Previous language attitude studies indicated that in many countries all over the world, English language learners perceived native accents either American or British, more positively than the non-native accents such as the Japanese, Korean, and Austrian accents. However, in Malaysia it is still unclear which accent Malaysian learners of English tend to perceive more positively (Pillai 2009. The verbal-guise technique and accent recognition item were adopted as indirect and direct instruments in gathering data to obtain data to clarify the inquiry. The sample includes 120 Malaysian university students and they were immersed in several speech accent situations to elicit feedback on their perceptions. Essentially two research questions are addressed: 1 What are Malaysian university students’ attitudes toward native and non-native English accents? 2 How familiar are students with accents?  The results indicated that the students had a bias towards in-group accent, meaning that they evaluated non-native lecturers’ accents more positively. These results supported the ‘social identity theory’ consistent with many previous language attitude studies of this nature. The Malaysian students were seen to be able to distinguish between native and non-native accents although there was much confusion between British and American accents.

Emergence of chikungunya seropositivity in healthy Malaysian adults residing in outbreak-free locations: Chikungunya seroprevalence results from the Malaysian Cohort

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2013-01-01

Background In 1998, Malaysia experienced its first chikungunya virus (CHIKV) outbreak in the suburban areas followed by another two in 2006 (rural areas) and 2008 (urban areas), respectively. Nevertheless, there is still a lack of documented data regarding the magnitude of CHIKV exposure in the Malaysian population. The aim of this study was to determine the extent of chikungunya virus infection in healthy Malaysian adults residing in outbreak-free locations. Methods A cross sectional study of chikungunya (CHIK) seroprevalence was carried out in 2009 amongst The Malaysian Cohort participants living in four states (Kuala Lumpur, Selangor, Pahang and Negeri Sembilan). A total of 945 participants were randomly identified for the study. Potential risk factors for CHIK infection were determined via questionnaires, and IgG antibodies against CHIK were detected by an enzyme-linked immunosorbent assay. Logistic regression identified risk factors associated with CHIK seropositivity, while geographical information system was used for visual and spatial analysis. Results From the 945 serum samples tested, 5.9% was positive for CHIK IgG. Being male, Malay, rural occupancy and Negeri Sembilan residency were identified as univariate predictors for CHIK seropositivity, while multivariate analysis identified being male and rural occupancy as risk factors. Conclusions This study provided evidence that CHIK is slowly emerging in Malaysia. Although the current baseline seroprevalence is low in this country, increasing number of CHIK cases reported to the Malaysia Ministry of Health imply the possibility of CHIK virus becoming endemic in Malaysia. PMID:23379541

Blocking mammalian target of rapamycin (mTOR) improves neuropathic pain evoked by spinal cord injury.

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Wang, Xiaoping; Li, Xiaojia; Huang, Bin; Ma, Shuai

2016-01-01

Spinal cord injury (SCI) is an extremely serious type of physical trauma observed in clinics. Neuropathic pain resulting from SCI has a lasting and significant impact on most aspects of daily life. Thus, a better understanding of the molecular pathways responsible for the cause of neuropathic pain observed in SCI is important to develop effective therapeutic agents and treatment strategies. Mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase that is well known for its critical roles in regulating protein synthesis and growth. Furthermore, compelling evidence supports the notion that widespread dysregulation of mTOR and its downstream pathways are involved in neuropathic pain. Thus, in this study we specifically examined the underlying mechanisms by which mTOR and its signaling pathways are involved in SCI-evoked neuropathic pain in a rat model. Overall, we demonstrated that SCI increased the protein expression of p-mTOR, and mTORmediated- phosphorylation of 4E-binding protein 4 (4E-BP1) and p70 ribosomal S6 protein kinase 1 (S6K1) in the superficial dorsal horn of the spinal cord. Also, we showed that blocking spinal mTOR by intrathecal injection of rapamycin significantly inhibited pain responses induced by mechanical and thermal stimulation. In addition, blocking spinal phosphatidylinositide 3-kinase (p-PI3K) pathway significantly attenuated activities of p-mTOR pathways as well as mechanical and thermal hyperalgesia in SCI rats. Moreover, blocking mTOR and PI3K decreased the enhanced levels of substance P and calcitonin gene-related peptide (CGRP) in the dorsal horn of SCI rats. We revealed specific signaling pathways leading to SCI-evoked neuropathic pain, including the activation of PI3K, mTOR and its downstream signaling pathways. Targeting one or more of these signaling molecules may present new opportunities for treatment and management of neuropathic pain often observed in patients with SCI.

Blocking mammalian target of rapamycin (mTOR improves neuropathic pain evoked by spinal cord injury

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Wang Xiaoping

2016-01-01

Full Text Available Spinal cord injury (SCI is an extremely serious type of physical trauma observed in clinics. Neuropathic pain resulting from SCI has a lasting and significant impact on most aspects of daily life. Thus, a better understanding of the molecular pathways responsible for the cause of neuropathic pain observed in SCI is important to develop effective therapeutic agents and treatment strategies. Mammalian target of rapamycin (mTOR is a serine/threonine protein kinase that is well known for its critical roles in regulating protein synthesis and growth. Furthermore, compelling evidence supports the notion that widespread dysregulation of mTOR and its downstream pathways are involved in neuropathic pain. Thus, in this study we specifically examined the underlying mechanisms by which mTOR and its signaling pathways are involved in SCI-evoked neuropathic pain in a rat model. Overall, we demonstrated that SCI increased the protein expression of p-mTOR, and mTORmediated- phosphorylation of 4E–binding protein 4 (4E-BP1 and p70 ribosomal S6 protein kinase 1 (S6K1 in the superficial dorsal horn of the spinal cord. Also, we showed that blocking spinal mTOR by intrathecal injection of rapamycin significantly inhibited pain responses induced by mechanical and thermal stimulation. In addition, blocking spinal phosphatidylinositide 3-kinase (p-PI3K pathway significantly attenuated activities of p-mTOR pathways as well as mechanical and thermal hyperalgesia in SCI rats. Moreover, blocking mTOR and PI3K decreased the enhanced levels of substance P and calcitonin gene-related peptide (CGRP in the dorsal horn of SCI rats. We revealed specific signaling pathways leading to SCI-evoked neuropathic pain, including the activation of PI3K, mTOR and its downstream signaling pathways. Targeting one or more of these signaling molecules may present new opportunities for treatment and management of neuropathic pain often observed in patients with SCI.

Obituary: Tor Hagfors, 1930-2007

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Aksnes, Kaare

2007-12-01

Tor Hagfors, a world leader in the use of radar techniques to observe ionospheres, surfaces and interiors of planetary bodies, died of heart-failure on 17 January 2007, in Puerto Rico, at the age of 76. He was born on 8 December 1930, in Oslo, Norway, and received his education there and in Trondheim, where he graduated with exceptionally good grades with a degree in technical physics from the Norwegian Institute of Technology (NTH) in 1955. Hagfors was then until 1963 employed at the Norwegian Defence Research Establishment (NDRE) where he worked mainly on scattering of high-frequency radio waves in the Earth's ionosphere. This work earned him a PhD in physics from the University of Oslo in 1959. With leave of absence from NDRE, he worked as a Research Associate at Stanford University in 1959/1960, developing a fundamental theory on incoherent scattering of radio waves from electrons in the ionosphere and also participating in radar studies of the Moon's surface in preparation for the later lunar landings. Back in Norway Hagfors continued his scattering studies but, finding that the opportunities for experimental work were limited there, he accepted in 1963 a position at the Massachusetts Institute of Technology's Lincoln Laboratory where he stayed until 1971, interrupted by two years as Director of the Jicamarca Radio Observatory near Lima in Peru 1967-1969. There he gained a reputation as a very inspiring and efficient leader who handled difficult negotiations with the Peruvian military junta very well. In 1971 Hagfors was appointed Director of Operations of the Arecibo Radio Observatory in Puerto Rico, a position that he held and executed in an excellent way until 1973. Although Tor had by now become a United States citizen with a brilliant scientific career, he chose to return to his alma mater, NTH, in Trondheim, where he worked as a Professor of Electronics between 1973 and 1982. From 1975 to 1982 he also served as Director of the European Incoherent Scatter

Characterizing the genetic risk for Type 2 diabetes in a Malaysian multi-ethnic cohort.

Science.gov (United States)

Abdullah, N; Abdul Murad, N A; Attia, J; Oldmeadow, C; Mohd Haniff, E A; Syafruddin, S E; Abd Jalal, N; Ismail, N; Ishak, M; Jamal, R; Scott, R J; Holliday, E G

2015-10-01

To characterize the association with Type 2 diabetes of known Type 2 diabetes risk variants in people in Malaysia of Malay, Chinese and Indian ancestry who participated in the Malaysian Cohort project. We genotyped 1604 people of Malay ancestry (722 cases, 882 controls), 1654 of Chinese ancestry (819 cases, 835 controls) and 1728 of Indian ancestry (851 cases, 877 controls). First, 62 candidate single-nucleotide polymorphisms previously associated with Type 2 diabetes were assessed for association via logistic regression within ancestral groups and then across ancestral groups using a meta-analysis. Second, estimated odds ratios were assessed for excess directional concordance with previously studied populations. Third, a genetic risk score aggregating allele dosage across the candidate single-nucleotide polymorphisms was tested for association within and across ancestral groups. After Bonferroni correction, seven individual single-nucleotide polymorphisms were associated with Type 2 diabetes in the combined Malaysian sample. We observed a highly significant excess in concordance of effect directions between Malaysian and previously studied populations. The genetic risk score was strongly associated with Type 2 diabetes in all Malaysian groups, explaining from 1.0 to 1.7% of total Type 2 diabetes risk variance. This study suggests there is substantial overlap of the genetic risk alleles underlying Type 2 diabetes in Malaysian and other populations. © 2015 The Authors. Diabetic Medicine © 2015 Diabetes UK.

Antidepressant action of ketamine via mTOR is mediated by inhibition of nitrergic Rheb degradation.

Science.gov (United States)

Harraz, M M; Tyagi, R; Cortés, P; Snyder, S H

2016-03-01

As traditional antidepressants act only after weeks/months, the discovery that ketamine, an antagonist of glutamate/N-methyl-D-aspartate (NMDA) receptors, elicits antidepressant actions in hours has been transformative. Its mechanism of action has been elusive, though enhanced mammalian target of rapamycin (mTOR) signaling is a major feature. We report a novel signaling pathway wherein NMDA receptor activation stimulates generation of nitric oxide (NO), which S-nitrosylates glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Nitrosylated GAPDH complexes with the ubiquitin-E3-ligase Siah1 and Rheb, a small G protein that activates mTOR. Siah1 degrades Rheb leading to reduced mTOR signaling, while ketamine, conversely, stabilizes Rheb that enhances mTOR signaling. Drugs selectively targeting components of this pathway may offer novel approaches to the treatment of depression.

Crosstalk between the Tor and Gcn2 pathways in response to different stresses.

Science.gov (United States)

Rødland, Gro Elise; Tvegård, Tonje; Boye, Erik; Grallert, Beáta

2014-01-01

Regulating growth and the cell cycle in response to environmental fluctuations is important for all organisms in order to maintain viability. Two major pathways for translational regulation are found in higher eukaryotes: the Tor signaling pathway and those operating through the eIF2α kinases. Studies from several organisms indicate that the two pathways are interlinked, in that Tor complex 1 (TORC1) negatively regulates the Gcn2 kinase. Furthermore, inactivation of TORC1 may be required for activation of Gcn2 in response to stress. Here, we use the model organism Schizosaccharomyces pombe to investigate this crosstalk further. We find that the relationship is more complex than previously thought. First, in response to UV irradiation and oxidative stress, Gcn2 is fully activated in the presence of TORC1 signaling. Second, during amino-acid starvation, activation of Gcn2 is dependent on Tor2 activity, and Gcn2 is required for timely inactivation of the Tor pathway. Our data show that the crosstalk between the two pathways varies with the actual stress applied.

Essential Oil Compositions of Malaysian Lauraceae: A Mini Review

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Wan Mohd Nuzul Hakimi Salleh, Farediah Ahmad * , Khong Heng Yen, Razauden Mohamed Zulkifli

2016-03-01

Full Text Available Essential oils have been largely employed for human need due to their antibacterial, antifungal and insecticidal activities. At present, approximately 3000 essential oils are known, 300 of which are commercially important. Essential oils or some of their components are used in perfumes and make-up products, sanitary products, dentistry, agriculture, as food preservers and additives, and as natural remedies. The essential oil compositions of Malaysian Lauraceae family have been investigated for many years. In the recent years, studies on the essential oils of the species have been progressing and many of them have reported interesting pharmacological activities. In this article, we summarized and updated the chemical compositions and biological activities of Malaysian Lauraceae. Throughout our literature review, only four genera which are Lindera, Beilschmiedia, Litsea, and Cinnamomum have been studied for their essential oil compositions in Malaysia. They were found to contain mainly safrole, eugenol, linalool, camphor, benzyl benzoate or cinnamaldehyde as major components. There were significant priorities to find out the details of the chemical compositions of the essential oils from Malaysian Lauraceae. Therefore, more clinical studies on the toxicity of the essential oil of the species are also crucial to ensure their safety and to assess their eligibility to be used as the sources of modern medicines.

Representation of Business Culture in Selected Malaysian Short Stories

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Zanirah Wahab

2016-11-01

Full Text Available Globalisation has brought numerous changes in all aspects of life especially in the economic sector. For the past few decades, the importance of economic growth and achievement has become the “obsession” of people around the world. Malaysia is no exception to this economic globalisation whirlwind. As well-known business hub with cutting edge technologies and blooming business enterprises, economic globalisation has shifted the way Malaysian society view things or connect with one another. This paper explores how business culture is represented in Malaysian short stories as well as examines the stand of the writers regarding the impact of economic globalisation on their society. In doing so, this paper compares and critically analyses three - selected short stories in the light of globalisation theory. The five main characteristics of globalisation namely, internationalisation, liberalisation, universalisation, westernisation and deterritorialisation are taken into account while dissecting these literary works. From the analysis, each writer voices out similar concerns regarding the impact of economic globalisation on their society. Malaysian fictions are preoccupied with the erosion of good values and the nation’s physical changes due to economic globalisation. The parallel stand demonstrates that regardless of their ethnicity and gender, they react uniformly to the changes.

mTOR at the Transmitting and Receiving Ends in Tumor Immunity.

Science.gov (United States)

Guri, Yakir; Nordmann, Thierry M; Roszik, Jason

2018-01-01

Cancer is a complex disease and a leading cause of death worldwide. Immunity is critical for cancer control. Cancer cells exhibit high mutational rates and therefore altered self or neo-antigens, eliciting an immune response to promote tumor eradication. Failure to mount a proper immune response leads to cancer progression. mTOR signaling controls cellular metabolism, immune cell differentiation, and effector function. Deregulated mTOR signaling in cancer cells modulates the tumor microenvironment, thereby affecting tumor immunity and possibly promoting carcinogenesis.

Project management at Heysham II and Torness

International Nuclear Information System (INIS)

Taylor, D.

1987-01-01

The National Nuclear Corporation (NNC) have contracts from the Central Electricity Generating Board (CEGB) and the South of Scotland Electricity Board (SSEB) for the design and construction of the AGR Nuclear Power Stations at Heysham II and Torness. Within these contracts, procurement and construction of the various components making up the Nuclear Island are managed by NNC as agents of the two generating boards. Other responsibilities are for the design of the whole station, preparation of the safety case and on-site management of the Nuclear Island at both stations. Additional responsibilities are included in the Torness contract such that NNC manage almost the whole of the site works. Construction of both stations started in August 1980 and power raising is expected to commence on time at the end of this year. Both stations are close to the original budget. This paper examines factors which have contributed to this success including the relationship between NNC, the contractors, clients and the safety authority. (author)

State of progress in Malaysian plant Taxonomy

NARCIS (Netherlands)

NN,

1948-01-01

Dr H.C.D. de Wit started a revision of Malaysian Bauhinia, this being part of his work on the Caesalpiniaceae of Malaysia; he is working in the Eijksherbarium, Leyden, Holland. Mr R.A. Blakelock, is revising the genus Evonymus at the Roy. Bot. Gardens, Kew-Surrey.

Cord Blood Cells Responses to IL2, IL7 and IL15 Cytokines for mTOR Expression

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Anahita Mohammadian

2017-04-01

Full Text Available Purpose: Mammalian target of rapamycin (mTORis important in hematopoiesis and affect cell growth,differentiation and survival. Although previous studies were identified the effect of cytokines on the mononuclear cells development however the cytokines effect on mTOR in cord blood mononuclear cells was unclear. The aim of this study was to evaluate mTOR expression in cord blood mononuclear and cord blood stem cells (CD34+ cells in culture conditions for lymphoid cell development. Methods: Isolation of The mononuclear cells (MNCs from umbilical cord blood were done with use of Ficollpaque density gradient. We evaluated cultured cord blood mononuclear and CD34+ cells in presece of IL2, IL7 and IL15 at distinct time points during 21 days by using flow cytometry. In this study, we presented the role of IL2, IL7 and IL15 on the expression of mTOR in cord blood cells. Results: mTOR expression were increased in peresence of IL2, IL7 and IL15 in day 14 and afterword reduced. However in persence of IL2 and IL15 expression of mTOR significantly reduced. mTOR expression in CD34+ cells decreased significantly from day7 to day 21 in culture. Conclusion: cytokines play important role in mTOR expression during hematopoiesis and development of cord blood mononuclear cells.

Loss of mTOR-Dependent Macroautophagy Causes Autistic-like Synaptic Pruning Deficits

OpenAIRE

Tang, Guomei; Gudsnuk, Kathryn; Kuo, Sheng-Han; Cotrina, Marisa L.; Rosoklija, Gorazd; Sosunov, Alexander; Sonders, Mark S.; Kanter, Ellen; Castagna, Candace; Yamamoto, Ai; Yue, Zhenyu; Arancio, Ottavio; Peterson, Bradley S.; Champagne, Frances; Dwork, Andrew J.

2014-01-01

Developmental alterations of excitatory synapses are implicated in autism spectrum disorders (ASDs). Here, we report increased dendritic spine density with reduced developmental spine pruning in layer V pyramidal neurons in postmortem ASD temporal lobe. These spine deficits correlate with hyperactivated mTOR and impaired autophagy. In Tsc2+/- ASD mice where mTOR is constitutively overactive, we observed postnatal spine pruning defects, blockade of autophagy, and ASD-like social...

Lithium protects against methamphetamine-induced neurotoxicity in PC12 cells via Akt/GSK3β/mTOR pathway

International Nuclear Information System (INIS)

Wu, Jintao; Zhu, Dexiao; Zhang, Jing; Li, Guibao; Liu, Zengxun; Sun, Jinhao

2015-01-01

Methamphetamine (MA) is neurotoxic, especially in dopaminergic neurons. Long-lasting exposure to MA causes psychosis and increases the risk of Parkinson's disease. Lithium (Li) is a known mood stabilizer and has neuroprotective effects. Previous studies suggest that MA exposure decreases the phosphorylation of Akt/GSK3β pathway in vivo, whereas Li facilitates the phosphorylation of Akt/GSK3β pathway. Moreover, GSK3β and mTOR are implicated in the locomotor sensitization induced by psychostimulants and mTOR plays a critical role in MA induced toxicity. However, the effect of MA on Akt/GSK3β/mTOR pathway has not been fully investigated in vitro. Here, we found that MA exposure significantly dephosphorylated Akt/GSK3β/mTOR pathway in PC12 cells. In addition, Li remarkably attenuated the dephosphorylation effect of MA exposure on Akt/GSK3β/mTOR pathway. Furthermore, Li showed obvious protective effects against MA toxicity and LY294002 (Akt inhibitor) suppressed the protective effects of Li. Together, MA exposure dephosphorylates Akt/GSK3β/mTOR pathway in vitro, while lithium protects against MA-induced neurotoxicity via phosphorylation of Akt/GSK3β/mTOR pathway. - Highlights: • Lithium protects against methamphetamine-induced neurotoxicity in vitro. • Methamphetamine exposure dephosphorylates Akt/GSK3β/mTOR pathway. • Lithium attenuates methamphetamine-induced toxicity via phosphorylating Akt/GSK3β/mTOR pathway

Lithium protects against methamphetamine-induced neurotoxicity in PC12 cells via Akt/GSK3β/mTOR pathway

Energy Technology Data Exchange (ETDEWEB)

Wu, Jintao; Zhu, Dexiao; Zhang, Jing; Li, Guibao [Department of Anatomy, School of Medicine, Shandong University, Jinan, Shandong, 250012 (China); Liu, Zengxun [Department of Psychiatry, School of Medicine, Shandong University, Jinan, Shandong, 250012 China (China); Sun, Jinhao, E-mail: sunjinhao@gmail.com [Department of Anatomy, School of Medicine, Shandong University, Jinan, Shandong, 250012 (China)

2015-09-25

Methamphetamine (MA) is neurotoxic, especially in dopaminergic neurons. Long-lasting exposure to MA causes psychosis and increases the risk of Parkinson's disease. Lithium (Li) is a known mood stabilizer and has neuroprotective effects. Previous studies suggest that MA exposure decreases the phosphorylation of Akt/GSK3β pathway in vivo, whereas Li facilitates the phosphorylation of Akt/GSK3β pathway. Moreover, GSK3β and mTOR are implicated in the locomotor sensitization induced by psychostimulants and mTOR plays a critical role in MA induced toxicity. However, the effect of MA on Akt/GSK3β/mTOR pathway has not been fully investigated in vitro. Here, we found that MA exposure significantly dephosphorylated Akt/GSK3β/mTOR pathway in PC12 cells. In addition, Li remarkably attenuated the dephosphorylation effect of MA exposure on Akt/GSK3β/mTOR pathway. Furthermore, Li showed obvious protective effects against MA toxicity and LY294002 (Akt inhibitor) suppressed the protective effects of Li. Together, MA exposure dephosphorylates Akt/GSK3β/mTOR pathway in vitro, while lithium protects against MA-induced neurotoxicity via phosphorylation of Akt/GSK3β/mTOR pathway. - Highlights: • Lithium protects against methamphetamine-induced neurotoxicity in vitro. • Methamphetamine exposure dephosphorylates Akt/GSK3β/mTOR pathway. • Lithium attenuates methamphetamine-induced toxicity via phosphorylating Akt/GSK3β/mTOR pathway.

Role of nutrients and mTOR signaling in the regulation of pancreatic progenitors development

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Lynda Elghazi

2017-06-01

Full Text Available Objective: Poor fetal nutrition increases the risk of type 2 diabetes in the offspring at least in part by reduced embryonic β-cell growth and impaired function. However, it is not entirely clear how fetal nutrients and growth factors impact β-cells during development to alter glucose homeostasis and metabolism later in life. The current experiments aimed to test the impact of fetal nutrients and growth factors on endocrine development and how these signals acting on mTOR signaling regulate β-cell mass and glucose homeostasis. Method: Pancreatic rudiments in culture were used to study the role of glucose, growth factors, and amino acids on β-cell development. The number and proliferation of pancreatic and endocrine progenitor were assessed in the presence or absence of rapamycin. The impact of mTOR signaling in vivo on pancreas development and glucose homeostasis was assessed in models deficient for mTOR or Raptor in Pdx1 expressing pancreatic progenitors. Results: We found that amino acid concentrations, and leucine in particular, enhance the number of pancreatic and endocrine progenitors and are essential for growth factor induced proliferation. Rapamycin, an mTORC1 complex inhibitor, reduced the number and proliferation of pancreatic and endocrine progenitors. Mice lacking mTOR in pancreatic progenitors exhibited hyperglycemia in neonates, hypoinsulinemia and pancreatic agenesis/hypoplasia with pancreas rudiments containing ductal structures lacking differentiated acinar and endocrine cells. In addition, loss of mTORC1 by deletion of raptor in pancreatic progenitors reduced pancreas size with reduced number of β-cells. Conclusion: Together, these results suggest that amino acids concentrations and in particular leucine modulates growth responses of pancreatic and endocrine progenitors and that mTOR signaling is critical for these responses. Inactivation of mTOR and raptor in pancreatic progenitors suggested that alterations in some of

Delayed recovery of skeletal muscle mass following hindlimb immobilization in mTOR heterozygous mice.

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Susan M Lang

Full Text Available The present study addressed the hypothesis that reducing mTOR, as seen in mTOR heterozygous (+/- mice, would exaggerate the changes in protein synthesis and degradation observed during hindlimb immobilization as well as impair normal muscle regrowth during the recovery period. Atrophy was produced by unilateral hindlimb immobilization and data compared to the contralateral gastrocnemius. In wild-type (WT mice, the gradual loss of muscle mass plateaued by day 7. This response was associated with a reduction in basal protein synthesis and development of leucine resistance. Proteasome activity was consistently elevated, but atrogin-1 and MuRF1 mRNAs were only transiently increased returning to basal values by day 7. When assessed 7 days after immobilization, the decreased muscle mass and protein synthesis and increased proteasome activity did not differ between WT and mTOR(+/- mice. Moreover, the muscle inflammatory cytokine response did not differ between groups. After 10 days of recovery, WT mice showed no decrement in muscle mass, and this accretion resulted from a sustained increase in protein synthesis and a normalization of proteasome activity. In contrast, mTOR(+/- mice failed to fully replete muscle mass at this time, a defect caused by the lack of a compensatory increase in protein synthesis. The delayed muscle regrowth of the previously immobilized muscle in the mTOR(+/- mice was associated with a decreased raptor•4EBP1 and increased raptor•Deptor binding. Slowed regrowth was also associated with a sustained inflammatory response (e.g., increased TNFα and CD45 mRNA during the recovery period and a failure of IGF-I to increase as in WT mice. These data suggest mTOR is relatively more important in regulating the accretion of muscle mass during recovery than the loss of muscle during the atrophy phase, and that protein synthesis is more sensitive than degradation to the reduction in mTOR during muscle regrowth.

Delayed recovery of skeletal muscle mass following hindlimb immobilization in mTOR heterozygous mice.

Science.gov (United States)

Lang, Susan M; Kazi, Abid A; Hong-Brown, Ly; Lang, Charles H

2012-01-01

The present study addressed the hypothesis that reducing mTOR, as seen in mTOR heterozygous (+/-) mice, would exaggerate the changes in protein synthesis and degradation observed during hindlimb immobilization as well as impair normal muscle regrowth during the recovery period. Atrophy was produced by unilateral hindlimb immobilization and data compared to the contralateral gastrocnemius. In wild-type (WT) mice, the gradual loss of muscle mass plateaued by day 7. This response was associated with a reduction in basal protein synthesis and development of leucine resistance. Proteasome activity was consistently elevated, but atrogin-1 and MuRF1 mRNAs were only transiently increased returning to basal values by day 7. When assessed 7 days after immobilization, the decreased muscle mass and protein synthesis and increased proteasome activity did not differ between WT and mTOR(+/-) mice. Moreover, the muscle inflammatory cytokine response did not differ between groups. After 10 days of recovery, WT mice showed no decrement in muscle mass, and this accretion resulted from a sustained increase in protein synthesis and a normalization of proteasome activity. In contrast, mTOR(+/-) mice failed to fully replete muscle mass at this time, a defect caused by the lack of a compensatory increase in protein synthesis. The delayed muscle regrowth of the previously immobilized muscle in the mTOR(+/-) mice was associated with a decreased raptor•4EBP1 and increased raptor•Deptor binding. Slowed regrowth was also associated with a sustained inflammatory response (e.g., increased TNFα and CD45 mRNA) during the recovery period and a failure of IGF-I to increase as in WT mice. These data suggest mTOR is relatively more important in regulating the accretion of muscle mass during recovery than the loss of muscle during the atrophy phase, and that protein synthesis is more sensitive than degradation to the reduction in mTOR during muscle regrowth.

Torin1-mediated TOR kinase inhibition reduces Wee1 levels and advances mitotic commitment in fission yeast and HeLa cells.

Science.gov (United States)

Atkin, Jane; Halova, Lenka; Ferguson, Jennifer; Hitchin, James R; Lichawska-Cieslar, Agata; Jordan, Allan M; Pines, Jonathon; Wellbrock, Claudia; Petersen, Janni

2014-03-15

The target of rapamycin (TOR) kinase regulates cell growth and division. Rapamycin only inhibits a subset of TOR activities. Here we show that in contrast to the mild impact of rapamycin on cell division, blocking the catalytic site of TOR with the Torin1 inhibitor completely arrests growth without cell death in Schizosaccharomyces pombe. A mutation of the Tor2 glycine residue (G2040D) that lies adjacent to the key Torin-interacting tryptophan provides Torin1 resistance, confirming the specificity of Torin1 for TOR. Using this mutation, we show that Torin1 advanced mitotic onset before inducing growth arrest. In contrast to TOR inhibition with rapamycin, regulation by either Wee1 or Cdc25 was sufficient for this Torin1-induced advanced mitosis. Torin1 promoted a Polo and Cdr2 kinase-controlled drop in Wee1 levels. Experiments in human cell lines recapitulated these yeast observations: mammalian TOR (mTOR) was inhibited by Torin1, Wee1 levels declined and mitotic commitment was advanced in HeLa cells. Thus, the regulation of the mitotic inhibitor Wee1 by TOR signalling is a conserved mechanism that helps to couple cell cycle and growth controls.

Glucose-ABL1-TOR Signaling Modulates Cell Cycle Tuning to Control Terminal Appressorial Cell Differentiation.

Science.gov (United States)

Marroquin-Guzman, Margarita; Sun, Guangchao; Wilson, Richard A

2017-01-01

The conserved target of rapamycin (TOR) pathway integrates growth and development with available nutrients, but how cellular glucose controls TOR function and signaling is poorly understood. Here, we provide functional evidence from the devastating rice blast fungus Magnaporthe oryzae that glucose can mediate TOR activity via the product of a novel carbon-responsive gene, ABL1, in order to tune cell cycle progression during infection-related development. Under nutrient-free conditions, wild type (WT) M. oryzae strains form terminal plant-infecting cells (appressoria) at the tips of germ tubes emerging from three-celled spores (conidia). WT appressorial development is accompanied by one round of mitosis followed by autophagic cell death of the conidium. In contrast, Δabl1 mutant strains undergo multiple rounds of accelerated mitosis in elongated germ tubes, produce few appressoria, and are abolished for autophagy. Treating WT spores with glucose or 2-deoxyglucose phenocopied Δabl1. Inactivating TOR in Δabl1 mutants or glucose-treated WT strains restored appressorium formation by promoting mitotic arrest at G1/G0 via an appressorium- and autophagy-inducing cell cycle delay at G2/M. Collectively, this work uncovers a novel glucose-ABL1-TOR signaling axis and shows it engages two metabolic checkpoints in order to modulate cell cycle tuning and mediate terminal appressorial cell differentiation. We thus provide new molecular insights into TOR regulation and cell development in response to glucose.

Defending Tor from Network Adversaries: A Case Study of Network Path Prediction

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Juen Joshua

2015-06-01

Full Text Available The Tor anonymity network has been shown vulnerable to traffic analysis attacks by autonomous systems (ASes and Internet exchanges (IXes, which can observe different overlay hops belonging to the same circuit. We evaluate whether network path prediction techniques provide an accurate picture of the threat from such adversaries, and whether they can be used to avoid this threat. We perform a measurement study by collecting 17.2 million traceroutes from Tor relays to destinations around the Internet. We compare the collected traceroute paths to predicted paths using state-of-the-art path inference techniques. We find that traceroutes present a very different picture, with the set of ASes seen in the traceroute path differing from the predicted path 80% of the time. We also consider the impact that prediction errors have on Tor security. Using a simulator to choose paths over a week, our traceroutes indicate a user has nearly a 100% chance of at least one compromise in a week with 11% of total paths containing an AS compromise and less than 1% containing an IX compromise when using default Tor selection. We find modifying the path selection to choose paths predicted to be safe lowers total paths with an AS compromise to 0.14% but still presents a 5–11% chance of at least one compromise in a week while making 5% of paths fail, with 96% of failures due to false positives in path inferences. Our results demonstrate more measurement and better path prediction is necessary to mitigate the risk of AS and IX adversaries to Tor.

mTOR up-regulation of PFKFB3 is essential for acute myeloid leukemia cell survival

International Nuclear Information System (INIS)

Feng, Yonghuai; Wu, Liusong

2017-01-01

Although mTOR (mammalian target of rapamycin) activation is frequently observed in acute myeloid leukemia (AML) patients, the precise function and the downstream targets of mTOR are poorly understood. Here we revealed that PFKFB3, but not PFKFB1, PFKFB2 nor PFKFB4 was a novel downstream substrate of mTOR signaling pathway as PFKFB3 level was augmented after knocking down TSC2 in THP1 and OCI-AML3 cells. Importantly, PFKFB3 silencing suppressed glycolysis and cell proliferation of TSC2 silencing OCI-AML3 cells and activated apoptosis pathway. These results suggested that mTOR up-regulation of PFKFB3 was essential for AML cells survival. Mechanistically, Rapamycin treatment or Raptor knockdown reduced the expression of PFKFB3 in TSC2 knockdown cells, while Rictor silencing did not have such effect. Furthermore, we also revealed that mTORC1 up-regulated PFKFB3 was dependent on hypoxia-inducible factor 1α (HIF1α), a positive regulator of glycolysis. Moreover, PFKFB3 inhibitor PFK15 and rapamycin synergistically blunted the AML cell proliferation. Taken together, PFKFB3 was a promising drug target in AML patients harboring mTOR hyper-activation.

Consumption intention toward ethnic food: determinants of Dayak food choice by Malaysians

OpenAIRE

Ting, Hiram; Tan, Sharon; Alexandra Nastassia, John

2017-01-01

Background: The awareness and trying of ethnic cuisine have increased due to the developing exchange of trade, movement of ethnicities across the globe, and tourist traveling opportunities. More people consume ethnic food for the appreciation of the culture and taste. Although the Dayaks are the largest indigenous group in Malaysia, little is done to date to explicate why Malaysians consume Dayak food. The present study aims to investigate the Dayak food choice of non-Dayak Malaysians and to ...

Impact of Antecedent Factors on Collaborative Technologies Usage among Academic Researchers in Malaysian Research Universities

Science.gov (United States)

Mohd Daud, Norzaidi; Zakaria, Halimi

2017-01-01

Purpose: The purpose of this paper is to investigate the impact of antecedent factors on collaborative technologies usage among academic researchers in Malaysian research universities. Design/methodology/approach: Data analysis was conducted on data collected from 156 academic researchers from five Malaysian research universities. This study…

[Algorithm of toxigenic genetically altered Vibrio cholerae El Tor biovar strain identification].

Science.gov (United States)

Smirnova, N I; Agafonov, D A; Zadnova, S P; Cherkasov, A V; Kutyrev, V V

2014-01-01

Development of an algorithm of genetically altered Vibrio cholerae biovar El Tor strai identification that ensures determination of serogroup, serovar and biovar of the studied isolate based on pheno- and genotypic properties, detection of genetically altered cholera El Tor causative agents, their differentiation by epidemic potential as well as evaluation of variability of key pathogenicity genes. Complex analysis of 28 natural V. cholerae strains was carried out by using traditional microbiological methods, PCR and fragmentary sequencing. An algorithm of toxigenic genetically altered V. cholerae biovar El Tor strain identification was developed that includes 4 stages: determination of serogroup, serovar and biovar based on phenotypic properties, confirmation of serogroup and biovar based on molecular-genetic properties determination of strains as genetically altered, differentiation of genetically altered strains by their epidemic potential and detection of ctxB and tcpA key pathogenicity gene polymorphism. The algorithm is based on the use of traditional microbiological methods, PCR and sequencing of gene fragments. The use of the developed algorithm will increase the effectiveness of detection of genetically altered variants of the cholera El Tor causative agent, their differentiation by epidemic potential and will ensure establishment of polymorphism of genes that code key pathogenicity factors for determination of origins of the strains and possible routes of introduction of the infection.

Spargel/dPGC-1 is a new downstream effector in the insulin-TOR signaling pathway in Drosophila.

Science.gov (United States)

Mukherjee, Subhas; Duttaroy, Atanu

2013-10-01

Insulin and target of rapamycin (TOR) signaling pathways converge to maintain growth so a proportionate body form is attained. Insufficiency in either insulin or TOR results in developmental growth defects due to low ATP level. Spargel is the Drosophila homolog of PGC-1, which is an omnipotent transcriptional coactivator in mammals. Like its mammalian counterpart, Spargel/dPGC-1 is recognized for its role in energy metabolism through mitochondrial biogenesis. An earlier study demonstrated that Spargel/dPGC-1 is involved in the insulin-TOR signaling, but a comprehensive analysis is needed to understand exactly which step of this pathway Spargel/PGC-1 is essential. Using genetic epistasis analysis, we demonstrated that a Spargel gain of function can overcome the TOR and S6K mediated cell size and cell growth defects in a cell autonomous manner. Moreover, the tissue-restricted phenotypes of TOR and S6k mutants are rescued by Spargel overexpression. We have further elucidated that Spargel gain of function sets back the mitochondrial numbers in growth-limited TOR mutant cell clones, which suggests a possible mechanism for Spargel action on cells and tissue to attain normal size. Finally, excess Spargel can ameliorate the negative effect of FoxO overexpression only to a limited extent, which suggests that Spargel does not share all of the FoxO functions and consequently cannot significantly rescue the FoxO phenotypes. Together, our observation established that Spargel/dPGC-1 is indeed a terminal effector in the insulin-TOR pathway operating below TOR, S6K, Tsc, and FoxO. This led us to conclude that Spargel should be incorporated as a new member of this growth-signaling pathway.

Educational Transition of East Malaysian Distance Learners.

Science.gov (United States)

Saw, K. G.; Awang, M. N.; Idrus, R. M.; Atan, H.; Azli, N. A.; Jaafar, I.; Rahman, Z. A.; Latiff, Z. A.

1999-01-01

Describes results of a study of the changing perceptions of East Malaysian distance learners studying at the Universiti Sains Malaysia. Highlights include students' perceptions of their study skills; and the impact of their studies on other areas of their life, including social obligations, recreation, families, health, finances, work, and…

Energy and Nutrient Intakes: Findings from the Malaysian Adult Nutrition Survey (MANS).

Science.gov (United States)

Mirnalini, K; Zalilah, M S; Safiah, M Y; Tahir, A; Siti Haslinda, M D; Siti Rohana, D; Khairul Zarina, M Y; Mohd Hasyami, S; Normah, H

2008-03-01

Nutrition surveys based on a representative sample of the Malaysian adult population have hitherto not been reported. In 2003, the Ministry of Health, Malaysia, conducted the Malaysian Adult Nutrition Survey (MANS), the first and largest nutrition survey in the country which aimed to provide detailed quantitative information on nutritional status, food and nutrient intakes, and physical activity pattern on a nationwide representative sample of adult subjects between the ages of 18 and 59 years. The survey covered four zones in Peninsular Malaysia (Central, Southern, Northern and East Coast), Sabah and Sarawak. This paper presents the mean and selected percentiles of energy and nutrient intake of 6886 subjects by selected demographic and socioeconomic characteristics. Energy contributions by macronutrients and dietary adequacy in relation to the Recommended Nutrient Intake for Malaysians are also described. Information on dietary intake was collected by trained nutritionists using a one day 24-hour diet recall. Dietary data were analysed using Nutritionist Pro, a diet analysis software and statistical analysis was carried out using the SPSS ver. 13.0. In most of the demographic and socioeconomic groups, males had higher mean energy (1776 kcal) and nutrient intake and percent achievement of RNI than females (1447 kcal). The proportions of calories derived from macronutrients were within the recommendations for a healthy diet. Intake of micronutrients such as iron, calcium and vitamin A was about 50% of RNI particularly in women. Sodium intake of Malaysians, not reported in earlier studies, is also made available. Under-reporting using the EI/BMR ratio was found in half of the population studied. The present study provides the first national estimates of energy and nutrient intake of the Malaysian adult population. Regular nutrition surveys are needed at the national level to provide valuable information on trends in food and nutrient intake, particularly among age

mTOR at the Transmitting and Receiving Ends in Tumor Immunity

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Yakir Guri

2018-03-01

Full Text Available Cancer is a complex disease and a leading cause of death worldwide. Immunity is critical for cancer control. Cancer cells exhibit high mutational rates and therefore altered self or neo-antigens, eliciting an immune response to promote tumor eradication. Failure to mount a proper immune response leads to cancer progression. mTOR signaling controls cellular metabolism, immune cell differentiation, and effector function. Deregulated mTOR signaling in cancer cells modulates the tumor microenvironment, thereby affecting tumor immunity and possibly promoting carcinogenesis.

Trauma torácico en la provincia de Cienfuegos. Estudio de tres años

OpenAIRE

Orozco Aguirre, Susan; Torres Ajá, Lidia; Otzoy Cún, Herson

2014-01-01

Fundamento: Los traumatismos torácicos presentan una alta incidencia en la sociedad actual y son de gran importancia por la naturaleza de los órganos que se localizan en el interior del tórax. Objetivo: caracterizar el comportamiento del trauma torácico. Métodos: estudio de serie de casos, realizado en el Servicio de Cirugía General del Hospital Dr. Gustavo Aldereguía Lima, de Cienfuegos. Se estudiaron los 184 pacientes atendidos por trauma torácico en los años 2009, 2010 y 2011, e ingresados...

The impact of derivatives on Malaysian stock market

Science.gov (United States)

Malim, M. R.; Halim, F. A.; Murad, A.; Maad, H. A.; Annuar, N. F. M.

2017-09-01

The essential of derivatives has been discovered by researchers over recent decade. However, the conclusions made regarding the impact of derivatives on stock market volatility remains debatable. The main objective of this study is to examine the impact of derivatives on Malaysian stock market volatility by exploring FTSE Bursa Malaysia Kuala Lumpur Composite Index Futures (BMD FKLI) using FBM KLCI as the underlying asset. Generalized Autoregressive Conditional Heteroskedasticity (GARCH) (1, 1) model was employed to realize the objective. The results have shown that the introduction of futures trading has decreased the volatility of Malaysian stock market. The volatility increased vigorously during the Asian financial crisis compared to the Global financial crisis. However, the role of futures as a risk transfer is agreed as it could improve the market by decreasing the volatility in the spot market.

Women in the Malaysian parliament: Do they matter?

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Ummu Atiyah Ahmad Zakuan

2010-12-01

Full Text Available This paper explores the impact of women’s representation in the lower house (Dewan Rakyat of the Malaysian Parliament. It is an attempt to see whether women representatives in the Dewan Rakyat are able to make any impact or difference in parliament, in the context of making policy output more women-friendly. Available studies conducted mainly in the West have shown that women legislators are more responsive to women’s interest than their male counterparts, developing distinctive sets of concerns and priorities and taking leading parts in formulating policies that favour women. Through textual analysis of nine years of the Malaysian Parliament (1999-2007, this paper examines the issues that have been introduced and discussed by the women and the impact they made in parliament. It also reveals the critical actors initiating or introducing women-related issues.

FACTORS INFLUENCING SEXUAL HARASSMENT IN THE MALAYSIAN WORKPLACE

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Lee Kum Chee

2007-01-01

Full Text Available This study examined the potential risks factors associated with sexually harassing behaviors within the framework of the four-factor model of sexual harassment. The factors examined are unprofessional work environment, skewed gender ratio in the workplace, knowledge of grievance procedure for sexual harassment, sexist attitudes among co-workers, privacy of workspace, physical attractiveness, dress manner of victims, job status, and sex roles. The dependent variable is incidence of sexual harassment which was evaluated using the Sexual Experience Questionnaire developed by Fitzgerald, Shullman, Bailey, Richards, Swecker, Gold, Ormerod, and Weitzman (1988. Data were collected from 657 women employees working in Malaysian organizations. The findings showed that the predictions of the four-factor model are also largely true in the case of the Malaysian workplace. The study also found that sexual harassment behaviors are fairly widespread in Malaysia.

Evaluating effectiveness and safety toward electronic cigarette among Malaysian vapers: One-month observational study

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Azizur Rahman

2016-01-01

Conclusion: A month follow-up showed a good smoking cessation rate among Malaysian vapers mainly in single users, whereas less number of quitters but the high reduction in tobacco cigarette consumption observed in dual users without any harmful effects. Furthermore, extended period studies are warranted to confirm its long-term safety and effectiveness among different Malaysian population.

Malaysian Students' Motivation towards Physics Learning

Science.gov (United States)

Saleh, Salmiza

2014-01-01

The purpose of this survey study was to examine the level of Malaysian students' motivation with regards to the learning of Physics at the secondary school level, and its influencing factors. The study was carried out on 337 Form Four students who took Physics as a subject, from six schools in a northern state of Malaysia--three from urban areas,…

Transient mTOR inhibition facilitates continuous growth of liver tumors by modulating the maintenance of CD133+ cell populations.

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Zhaojuan Yang

Full Text Available The mammalian target of the rapamycin (mTOR pathway, which drives cell proliferation, is frequently hyperactivated in a variety of malignancies. Therefore, the inhibition of the mTOR pathway has been considered as an appropriate approach for cancer therapy. In this study, we examined the roles of mTOR in the maintenance and differentiation of cancer stem-like cells (CSCs, the conversion of conventional cancer cells to CSCs and continuous tumor growth in vivo. In H-Ras-transformed mouse liver tumor cells, we found that pharmacological inhibition of mTOR with rapamycin greatly increased not only the CD133+ populations both in vitro and in vivo but also the expression of stem cell-like genes. Enhancing mTOR activity by over-expressing Rheb significantly decreased CD133 expression, whereas knockdown of the mTOR yielded an opposite effect. In addition, mTOR inhibition severely blocked the differentiation of CD133+ to CD133- liver tumor cells. Strikingly, single-cell culture experiments revealed that CD133- liver tumor cells were capable of converting to CD133+ cells and the inhibition of mTOR signaling substantially promoted this conversion. In serial implantation of tumor xenografts in nude BALB/c mice, the residual tumor cells that were exposed to rapamycin in vivo displayed higher CD133 expression and had increased secondary tumorigenicity compared with the control group. Moreover, rapamycin treatment also enhanced the level of stem cell-associated genes and CD133 expression in certain human liver tumor cell lines, such as Huh7, PLC/PRC/7 and Hep3B. The mTOR pathway is significantly involved in the generation and the differentiation of tumorigenic liver CSCs. These results may be valuable for the design of more rational strategies to control clinical malignant HCC using mTOR inhibitors.

Phosphatidylinositol-3-OH kinase and nutrient-sensing mTOR pathways control T lymphocyte trafficking

NARCIS (Netherlands)

Sinclair, Linda V.; Finlay, David; Feijoo, Carmen; Cornish, Georgina H.; Gray, Alex; Ager, Ann; Okkenhaug, Klaus; Hagenbeek, Thijs J.; Spits, Hergen; Cantrell, Doreen A.

2008-01-01

Phosphatidylinositol-3-OH kinase (PI(3)K) and the nutrient sensor mTOR are evolutionarily conserved regulators of cell metabolism. Here we show that PI(3)K and mTOR determined the repertoire of adhesion and chemokine receptors expressed by T lymphocytes. The key lymph node-homing receptors CD62L

The political economy of Malaysian federalism: Economic development, public policy and conflict containment

OpenAIRE

Jomo, K. S.; Hui, Wee Chong

2002-01-01

Conflicts within the Malaysian federation have been rooted in socio-economic disparities and the struggle for control of natural resource rents, which State Governments previously had exclusive control over, as originally provided for by the federal constitution. The advance of fiscal centralization since then has also aggravated federal-state tensions, which have been relatively ignored due to the long-standing Malaysian pre-occupation with inter-ethnic tensions. Inter-regional resource tran...

Malaysian water sector reform : policy and performance

NARCIS (Netherlands)

Kim, C.T.

2012-01-01

One of the measures that can help developing countries in meeting Target 10 of the Millennium Development Goals – halving the number of people without access to water and adequate sanitation by 2015 – is through a water sector reform. In this research the Malaysian water sector reform is

Analysis of volatile compounds of Malaysian Tualang ( Koompassia ...

African Journals Online (AJOL)

Analysis of volatile compounds of Malaysian Tualang ( Koompassia excelsa ) honey using gas chromatography mass spectrometry. ... Other classes of chemical compounds detected included acids, aldehydes, alcohols, ketones, terpenes, furans and a miscellaneous group. Methanol yielded the highest number of extracted ...

Oral cancer awareness and its determinants among a selected Malaysian population.

Science.gov (United States)

Ghani, Wan Maria Nabillah; Doss, Jennifer Geraldine; Jamaluddin, Marhazlinda; Kamaruzaman, Dinan; Zain, Rosnah Binti

2013-01-01

To assess oral cancer awareness, its associated factors and related sources of information among a selected group of Malaysians. A cross-sectional survey was conducted on all Malaysian ethnic groups aged ≥15 years old at eight strategically chosen shopping malls within a two week time period. Data were analysed using chi-square tests and multiple logistic regression. Significance level was set at αcancer. Smoking was the most (92.4%) recognized high risk habit. Similar levels of awareness were seen for unhealed ulcers (57.3%) and red/white patches (58.0%) as signs of oral cancer. Age, gender, ethnicity, marital status, education, occupation and income were significantly associated with oral cancer awareness (pawareness regarding the risk habits, early signs and symptoms, and the benefits of detecting this disease at an early stage. Mass media and health campaigns were the main sources of information about oral cancer. In our Malaysian population, gender and age were significantly associated with the awareness of early signs and symptoms and prevention of oral cancer, respectively.

FK866-induced NAMPT inhibition activates AMPK and downregulates mTOR signaling in hepatocarcinoma cells

Energy Technology Data Exchange (ETDEWEB)

Schuster, Susanne, E-mail: Susanne.Schuster@medizin.uni-leipzig.de [Center for Pediatric Research Leipzig, University Hospital for Children and Adolescents, Faculty of Medicine, University of Leipzig, Liebigstr. 21, 04103 Leipzig (Germany); Penke, Melanie; Gorski, Theresa [Center for Pediatric Research Leipzig, University Hospital for Children and Adolescents, Faculty of Medicine, University of Leipzig, Liebigstr. 21, 04103 Leipzig (Germany); Gebhardt, Rolf [Institute of Biochemistry, Faculty of Medicine, University of Leipzig, Johannisallee 30, 04103 Leipzig (Germany); Weiss, Thomas S. [Children' s University Hospital, University of Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg (Germany); Kiess, Wieland; Garten, Antje [Center for Pediatric Research Leipzig, University Hospital for Children and Adolescents, Faculty of Medicine, University of Leipzig, Liebigstr. 21, 04103 Leipzig (Germany)

2015-03-06

Background: Nicotinamide phosphoribosyltransferase (NAMPT) is the key enzyme of the NAD salvage pathway starting from nicotinamide. Cancer cells have an increased demand for NAD due to their high proliferation and DNA repair rate. Consequently, NAMPT is considered as a putative target for anti-cancer therapies. There is evidence that AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) become dysregulated during the development of hepatocellular carcinoma (HCC). Here, we investigated the effects of NAMPT inhibition by its specific inhibitor FK866 on the viability of hepatocarcinoma cells and analyzed the effects of FK866 on the nutrient sensor AMPK and mTOR complex1 (mTORC1) signaling. Results: FK866 markedly decreased NAMPT activity and NAD content in hepatocarcinoma cells (Huh7 cells, Hep3B cells) and led to delayed ATP reduction which was associated with increased cell death. These effects could be abrogated by administration of nicotinamide mononucleotide (NMN), the enzyme product of NAMPT. Our results demonstrated a dysregulation of the AMPK/mTOR pathway in hepatocarcinoma cells compared to non-cancerous hepatocytes with a higher expression of mTOR and a lower AMPKα activation in hepatocarcinoma cells. We found that NAMPT inhibition by FK866 significantly activated AMPKα and inhibited the activation of mTOR and its downstream targets p70S6 kinase and 4E-BP1 in hepatocarcinoma cells. Non-cancerous hepatocytes were less sensitive to FK866 and did not show changes in AMPK/mTOR signaling after FK866 treatment. Conclusion: Taken together, these findings reveal an important role of the NAMPT-mediated NAD salvage pathway in the energy homeostasis of hepatocarcinoma cells and suggest NAMPT inhibition as a potential treatment option for HCC. - Highlights: • FK866 increases cell death in p53-deficient hepatocarcinoma cells. • AMPK/mTOR signaling is dysregulated in hepatocarcinoma cells. • FK866-induced NAMPT inhibition activates AMPK�

FK866-induced NAMPT inhibition activates AMPK and downregulates mTOR signaling in hepatocarcinoma cells

International Nuclear Information System (INIS)

Schuster, Susanne; Penke, Melanie; Gorski, Theresa; Gebhardt, Rolf; Weiss, Thomas S.; Kiess, Wieland; Garten, Antje

2015-01-01

Background: Nicotinamide phosphoribosyltransferase (NAMPT) is the key enzyme of the NAD salvage pathway starting from nicotinamide. Cancer cells have an increased demand for NAD due to their high proliferation and DNA repair rate. Consequently, NAMPT is considered as a putative target for anti-cancer therapies. There is evidence that AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) become dysregulated during the development of hepatocellular carcinoma (HCC). Here, we investigated the effects of NAMPT inhibition by its specific inhibitor FK866 on the viability of hepatocarcinoma cells and analyzed the effects of FK866 on the nutrient sensor AMPK and mTOR complex1 (mTORC1) signaling. Results: FK866 markedly decreased NAMPT activity and NAD content in hepatocarcinoma cells (Huh7 cells, Hep3B cells) and led to delayed ATP reduction which was associated with increased cell death. These effects could be abrogated by administration of nicotinamide mononucleotide (NMN), the enzyme product of NAMPT. Our results demonstrated a dysregulation of the AMPK/mTOR pathway in hepatocarcinoma cells compared to non-cancerous hepatocytes with a higher expression of mTOR and a lower AMPKα activation in hepatocarcinoma cells. We found that NAMPT inhibition by FK866 significantly activated AMPKα and inhibited the activation of mTOR and its downstream targets p70S6 kinase and 4E-BP1 in hepatocarcinoma cells. Non-cancerous hepatocytes were less sensitive to FK866 and did not show changes in AMPK/mTOR signaling after FK866 treatment. Conclusion: Taken together, these findings reveal an important role of the NAMPT-mediated NAD salvage pathway in the energy homeostasis of hepatocarcinoma cells and suggest NAMPT inhibition as a potential treatment option for HCC. - Highlights: • FK866 increases cell death in p53-deficient hepatocarcinoma cells. • AMPK/mTOR signaling is dysregulated in hepatocarcinoma cells. • FK866-induced NAMPT inhibition activates AMPK�

AirAsia In The Malaysian Domestic Airline Market: Empirical Analysis Of Strategy

OpenAIRE

Mok Kim Man; Jainurin Bin Justine

2011-01-01

This paper will examine the results of the strategic actions of AirAsia in the Malaysian domestic airline market. Firstly, the paper will provide a general background of the airline industry, in particular the Malaysian domestic airline market and a summary of an analysis of the industry using Michael Porters Five Forces Analysis. Secondly, the paper will provide a brief background of AirAsia and Malaysia Airlines. Thirdly, the paper will analyse the results of AirAsias strategy vis--vis oper...

The mTOR inhibitor sirolimus suppresses renal, hepatic, and cardiac tissue cellular respiration.

Science.gov (United States)

Albawardi, Alia; Almarzooqi, Saeeda; Saraswathiamma, Dhanya; Abdul-Kader, Hidaya Mohammed; Souid, Abdul-Kader; Alfazari, Ali S

2015-01-01

The purpose of this in vitro study was to develop a useful biomarker (e.g., cellular respiration, or mitochondrial O2 consumption) for measuring activities of mTOR inhibitors. It measured the effects of commonly used immunosuppressants (sirolimus-rapamycin, tacrolimus, and cyclosporine) on cellular respiration in target tissues (kidney, liver, and heart) from C57BL/6 mice. The mammalian target of rapamycin (mTOR), a serine/ threonine kinase that supports nutrient-dependent cell growth and survival, is known to control energy conversion processes within the mitochondria. Consistently, inhibitors of mTOR (e.g., rapamycin, also known as sirolimus or Rapamune®) have been shown to impair mitochondrial function. Inhibitors of the calcium-dependent serine/threonine phosphatase calcineurin (e.g., tacrolimus and cyclosporine), on the other hand, strictly prevent lymphokine production leading to a reduced T-cell function. Sirolimus (10 μM) inhibited renal (22%, P=0.002), hepatic (39%, Prespiration. Tacrolimus and cyclosporine had no or minimum effects on cellular respiration in these tissues. Thus, these results clearly demonstrate that impaired cellular respiration (bioenergetics) is a sensitive biomarker of the immunosuppressants that target mTOR.

Comparison of different tube-of-response (TOR) models for resolution recovery in PET image reconstruction for the Philips Ingenuity TF PET/MR

International Nuclear Information System (INIS)

Lougovski, Alexandr; Hofheinz, Frank; Van Den Hoff, Jorg

2015-01-01

Recently, we have proposed a method for on-the-fly system matrix computation where the tube-of-response (TOR) is approximated as a cylinder with constant density (TORCD) and the cubic voxels are replaced by spheres. We could show that with this model the PET image quality can be notably improved compared to the vendor provided image reconstruction of our Philips Ingenuity-TF PET/MR. In this work we address the question whether image quality can be further improved by using a variable density TOR (TOR-VD). The radial variability of TOR-VD was modelled by a Kaiser-Bessel function. Free parameters of this density model were used to optimize image properties regarding resolution, noise, and Gibbs artifacts. Additional, a TOR-VD model accounting for position dependent effects along the TOR caused by the finite solid angles of the detectors is under investigation. Phantom measurement were performed with a Philips Ingenuity-TF PET/MR scanner. Listmode data were reconstructed using TOR-CD and TORVD, respectively on two different grids with cubic voxel size of 2 mm and 4 mm. Image quality was assessed with resolution-noise curves and investigation of the radial position dependence of the spatial resolution. For 2 mm voxels, TOR-VD consistently yields a slight improvement of the investigated image quality measures compared to TOR-CD. For 4 mm voxels both models lead essentially to the same results. These findings can be understood as a consequence of the relative size of voxel and TOR. For typical whole body studies (4 mm voxel size) a variable TOR does not improve image quality beyond what is achievable with a constant density TOR. For smaller voxel size the image quality can indeed be somewhat improved with a variable TOR but at the expense of drastically increased computation time.

Comparison of different tube-of-response (TOR) models for resolution recovery in PET image reconstruction for the Philips Ingenuity TF PET/MR

Energy Technology Data Exchange (ETDEWEB)

Lougovski, Alexandr; Hofheinz, Frank; Van Den Hoff, Jorg [Helmholtz-Center Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer Research, PET Center, Dresden (Germany)

2015-05-18

Recently, we have proposed a method for on-the-fly system matrix computation where the tube-of-response (TOR) is approximated as a cylinder with constant density (TORCD) and the cubic voxels are replaced by spheres. We could show that with this model the PET image quality can be notably improved compared to the vendor provided image reconstruction of our Philips Ingenuity-TF PET/MR. In this work we address the question whether image quality can be further improved by using a variable density TOR (TOR-VD). The radial variability of TOR-VD was modelled by a Kaiser-Bessel function. Free parameters of this density model were used to optimize image properties regarding resolution, noise, and Gibbs artifacts. Additional, a TOR-VD model accounting for position dependent effects along the TOR caused by the finite solid angles of the detectors is under investigation. Phantom measurement were performed with a Philips Ingenuity-TF PET/MR scanner. Listmode data were reconstructed using TOR-CD and TORVD, respectively on two different grids with cubic voxel size of 2 mm and 4 mm. Image quality was assessed with resolution-noise curves and investigation of the radial position dependence of the spatial resolution. For 2 mm voxels, TOR-VD consistently yields a slight improvement of the investigated image quality measures compared to TOR-CD. For 4 mm voxels both models lead essentially to the same results. These findings can be understood as a consequence of the relative size of voxel and TOR. For typical whole body studies (4 mm voxel size) a variable TOR does not improve image quality beyond what is achievable with a constant density TOR. For smaller voxel size the image quality can indeed be somewhat improved with a variable TOR but at the expense of drastically increased computation time.

Hypothalamic roles of mTOR complex I: integration of nutrient and hormone signals to regulate energy homeostasis.

Science.gov (United States)

Hu, Fang; Xu, Yong; Liu, Feng

2016-06-01

Mammalian or mechanistic target of rapamycin (mTOR) senses nutrient, energy, and hormone signals to regulate metabolism and energy homeostasis. mTOR activity in the hypothalamus, which is associated with changes in energy status, plays a critical role in the regulation of food intake and body weight. mTOR integrates signals from a variety of "energy balancing" hormones such as leptin, insulin, and ghrelin, although its action varies in response to these distinct hormonal stimuli as well as across different neuronal populations. In this review, we summarize and highlight recent findings regarding the functional roles of mTOR complex 1 (mTORC1) in the hypothalamus specifically in its regulation of body weight, energy expenditure, and glucose/lipid homeostasis. Understanding the role and underlying mechanisms behind mTOR-related signaling in the brain will undoubtedly pave new avenues for future therapeutics and interventions that can combat obesity, insulin resistance, and diabetes. Copyright © 2016 the American Physiological Society.

PREDICTION OF THE COURSE OF OSTEOARTHROSIS FROM mTOR (MAMMALIAN TARGET OF RAPAMYCIN GENE EXPRESSION

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E V Chetina

2012-01-01

Results. Analysis of gene expression in the outpatients with OA identified two subgroups: in one subgroup (n = 13 mTOR expression was considerably much less than that in the control group; the expression of ATG1 and p21 did not differ greatly from the control and that of caspase 3 and TNF-α was significantly higher. The other outpatients (n = 20 and all the examined patients needing endoprosthetic replacement were ascertained to have a higher gene expression of mTOR, ATG1, p21, caspase 3, and TNF-α than in the control group. Before endoprosthetic replacement, severe joint destruction in patients with OA was associated with enhanced gene expression of mTOR, ATG1, p21, and caspase 3. Conclusion. In early-stage disease, increased mTOR gene expression may serve as a prognostic marker of the severity of the disease and articular cartilage destruction.

Review of inspection of Torness reactor internals using remote techniques

International Nuclear Information System (INIS)

Dynan, J.

1993-01-01

Inspection of reactor internals is increasingly being achieved by deployment of cameras into areas of sometimes high radiation fields using manipulators. The manipulators have been developed over a number of years and from a variety of sources and those provided at Torness can maybe be seen to be the state of the art development of such machines for AGRS. Torness and Heysham 2 reactors were specifically designed for inspection using remote techniques and special facilities have been provided for this purpose. This paper is written by an operator and not a manipulator specialist and is intended to show what the operator needs versus what the designer gave him. (author)

Issues and Economic Role of Waqf In Higher Education Institution: Malaysian Experience

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Farra Munna Harun

2016-02-01

Full Text Available As early as 1980, the Malaysianfederal government’s spending on education, was the highest in East Asia andhigher than the OECD average of 3.4% of GDP. This demonstrates that theMalaysian Government has big expenses from educational sector and respectivelyis amenability for Malaysian economic budget. In other side Waqf in Malaysia isone of large financial source that has not been fully explored. By using qualitative methodology through content analysis this paper attempt to explore the issues andeconomic role of Waqf in Malaysia, especially in Higher Education Institution(HEI and attempt to study how Waqf fund empowering the education. Thisstudy found that taking the que from the institutions of Waqf, the explorationand development of waqf fund can be exalarate through the formation of formalorganizations at state and federal level and rearrange the Malaysian educationalbudget and policy to support the better quality of HEI.DOI: 10.15408/aiq.v8i1.2514 

The factors that influence job satisfaction among royal Malaysian customs department employee

Science.gov (United States)

Ammar Shafi, Muhammad; Saifullah Rusiman, Mohd; Nor, Maria Elena; Khamis, Azme; Nabilah Syuhada Abdullah, Siti; Syafiq Azmi, Mohd; Sakinah Zainal Abidin, Munirah; Ali, Maselan

2018-04-01

This research aims to spot the factors that influence job satisfaction among Royal Malaysian Customs Department employees. Primary data was used in this research and it was collected from the employees who work in five different departments at Royal Malaysian Customs Department Tower Johor. Those departments were customs department, Internal Taxes, Technical Services, Management and Prevention. The research used stratified random sampling to collect the sample and Structural Equation Modelling (SEM) to measure the relationship between variables using AMOS software. About 127 employees are selected as the respondents from five departments to represent the sample. The result showed that ‘Organizational Commitment’ (p-value = 0.001) has significant and direct effect toward job satisfaction compared to the ‘Stress Condition’ (p-value = 0.819) and ‘Motivation’ factor (p-value = 0.978). It was also concluded that ‘Organizational Commitment’ was the most influential factor toward job satisfaction among Royal Malaysian Customs Department employees at Tower Custom Johor, Johor Bahru.

Islamic Content On Malaysian TV: A Case study of TV Al Hijrah

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Juliana Abdul Wahab

2017-12-01

Full Text Available Religion and media are converging and frequently becoming a subject matter for news content and popular entertainment programmes in television and film, publishing, music as well as the new media. Religion, arguably has become part and parcel of the media environment today. In Malaysian context, during the millennium era, many locally produced ‘Islamic programmes’ started to gain popularity among Malaysian audience especially within the entertainment genre such as television drama. With the establishment of Malaysian first Islamic free-to-air television, TV Al Hijrah in 2010, this paper aims to understand the nature of Islamic content available on the station. The preliminary findings of this paper suggest that there are varieties of television programmes created and aired on TV Al Hijrah cutting across different genres meant for disseminating Islam as a way of life. Programmes available are mainly about showcasing the values of Islamic teaching and beliefs with the ultimate goal to highlight Islam as a beautiful and peaceful religion.

Defining Malaysian Knowledge Society: Results from the Delphi Technique

Science.gov (United States)

Hamid, Norsiah Abdul; Zaman, Halimah Badioze

This paper outlines the findings of research where the central idea is to define the term Knowledge Society (KS) in Malaysian context. The research focuses on three important dimensions, namely knowledge, ICT and human capital. This study adopts a modified Delphi technique to seek the important dimensions that can contribute to the development of Malaysian's KS. The Delphi technique involved ten experts in a five-round iterative and controlled feedback procedure to obtain consensus on the important dimensions and to verify the proposed definition of KS. The finding shows that all three dimensions proposed initially scored high and moderate consensus. Round One (R1) proposed an initial definition of KS and required comments and inputs from the panel. These inputs were then used to develop items for a R2 questionnaire. In R2, 56 out of 73 items scored high consensus and in R3, 63 out of 90 items scored high. R4 was conducted to re-rate the new items, in which 8 out of 17 items scored high. Other items scored moderate consensus and no item scored low or no consensus in all rounds. The final round (R5) was employed to verify the final definition of KS. Findings and discovery of this study are significant to the definition of KS and the development of a framework in the Malaysian context.

Malaysian public perception towards nuclear power energy-related issues

Science.gov (United States)

Misnon, Fauzan Amin; Hu, Yeoh Siong; Rahman, Irman Abd.; Yasir, Muhamad Samudi

2017-01-01

Malaysia had considered nuclear energy as an option for future electricity generation during the 9th Malaysia Development Plan. Since 2009, Malaysia had implemented a number of important preparatory steps towards this goal, including the establishment of Nuclear Power Corporation of Malaysia (MNPC) as first Nuclear Energy Programme Implementing Organization (NEPIO) in Malaysia. In light of the establishment of MNPC, the National Nuclear Policy was formulated in 2010 and a new comprehensive nuclear law to replace the existing Atomic Energy Licensing Act (Act 304) is currently in the pipeline. Internationally, public acceptance is generally used to gauge the acceptance of nuclear energy by the public whenever a government decides to engage in nuclear energy. A public survey was conducted in between 14 March 2016 to 10 May 2016 focusing on the Malaysian public acceptance and perception towards the implementation of nuclear energy in Malaysia. The methodology of this research was aim on finding an overview of the general knowledge, public-relation recommendation, perception and acceptance of Malaysian towards the nuclear power development program. The combination of information gathered from this study can be interpreted as an indication of the complexity surrounding the development of nuclear energy and its relationship with the unique background of Malaysian demography. This paper will focus mainly on energy-related section in the survey in comparison with nuclear energy.

Prognostic and predictive value of p-Akt, EGFR, and p-mTOR in early breast cancer

Energy Technology Data Exchange (ETDEWEB)

Lazaridis, Georgios; Lambaki, Sofia [Hospital, Department of Pathology, Thessaloniki (Greece); Karayannopoulou, Georgia [Aristotle Univ. of Thessaloniki School of Medicine, Thessaloniki (Greece). Dept. of Pathology; Eleftheraki, Anastasia G. [Data Office, Athens (Greece). Section of Biostatistics; Papaspirou, Irene [Alexandra Hospital, Athens (Greece). Dept. of Pathology; Bobos, Mattheos [Aristotle Univ. of Thessaloniki School of Medicine, Thessaloniki (Greece). Lab. of Molecular Oncology; Efstratiou, Ioannis [Papageorgiou Hospital, Thessaloniki (Greece). Dept. of Pathology; Pentheroudakis, George [Ioannina Univ. Hospital, Ioannina (Greece). Dept. of Medical Oncology; Zamboglou, Nikolaos [Klinikum Offenbach (Germany). Dept. of Radiation Oncology; Fountzilas, George [Hospital, Department of Pathology, Thessaloniki (Greece); Aristotle Univ. of Thessaloniki School of Medicine, Thessaloniki (Greece). Lab. of Molecular Oncology

2014-07-15

There are scarce data available on the prognostic/predictive value of p-Akt and p-mTOR protein expression in patients with high-risk early breast cancer. Formalin-fixed paraffin-embedded (FFPE) tumor tissue samples from 997 patients participating in two adjuvant phase III trials were assessed for EGFR, PTEN, p-Akt, p-mTOR protein expression, and PIK3CA mutational status. These markers were evaluated for associations with each other and with selected patient and tumor characteristics, immunohistochemical subtypes, disease-free survival (DFS), and overall survival (OS). p-mTOR protein expression was negatively associated with EGFR and positively associated with PTEN, with p-Akt473, and with the presence of PIK3CA mutations. EGFR expression was positively associated with p-Akt473, p-Akt308, and PIK3CA wild-type tumors. Finally, p-Akt308 was positively associated with p-Akt473 expression. In univariate analysis, EGFR (p = 0.016) and the coexpression of EGFR and p-mTOR (p = 0.015) were associated with poor OS. Among patients with p-Akt308-negative or low-expressing tumors, those treated with hormonal therapy were associated with decreased risk for both relapse and death (p = 0.013 and p < 0.001, respectively). In the subgroup of patients with locoregional relapse, positive EGFR and mTOR protein expression was found to be associated with increased (p = 0.034) and decreased (p < 0.001) risk for earlier relapse, respectively. In multivariate analysis, low levels of p-Akt308 and the coexpression of EGFR and p-mTOR retained their prognostic value. Low protein expression of p-Akt308 was associated with improved DFS and OS among patients treated with hormonal therapy following adjuvant chemotherapy. Coexpression of EGFR and p-mTOR was associated with worse OS. (orig.) [German] Geringe Daten existieren ueber den prognostischen/praediktiven Wert der p-Akt- und p-mTOR-Proteinexpression bei Patienten mit ''High-risk''-Mammakarzinom im Fruehstadium

Biotechnology issues in four Malaysian mainstream newspapers

African Journals Online (AJOL)

Jane

2011-09-30

Sep 30, 2011 ... Biotechnology has been identified as the new engine of growth for the transformation of Malaysia into a developed nation by 2020. The objective of this paper is to analyze the impact of National Policy on biotechnology on media reporting in four Malaysian newspapers. Towards this end, a content analysis.

mTOR in squamous cell carcinoma of the oesophagus: a potential target for molecular therapy?

NARCIS (Netherlands)

Boone, J.; ten Kate, F. J. W.; Offerhaus, G. J. A.; van Diest, P. J.; Borel Rinkes, I. H. M.; van Hillegersberg, R.

2008-01-01

AIMS: The mammalian target of rapamycin (mTOR), an important regulator of protein translation and cell proliferation, is activated in various malignancies. In a randomised controlled trial of advanced renal cell carcinoma patients, targeted therapy to mTOR by means of rapamycin analogues has been

Intercultural Communication and the Decision-Making Process: Americans and Malaysians in a Cooperative University Setting.

Science.gov (United States)

Wilhelm, Kim Hughes

A study investigated the application of Geert Hofstede's theory of cultural dimensions in management to the situation of Malaysian (n=8) and American (n=4) instructors in implementing a new English-as-a-Second-Language curriculum in Malaysia. American and Malaysian cultures are compared on four dimensions: social differentiation by gender; desire…

Marketing Malaysian enterprises in Brazil: what is the government ...

African Journals Online (AJOL)

Marketing Malaysian enterprises in Brazil: what is the government doing? ... Marketing products and services abroad is essential for the new ventures growth and continuous existence. ... EMAIL FREE FULL TEXT EMAIL FREE FULL TEXT

Systemic and Nonrenal Adverse Effects Occurring in Renal Transplant Patients Treated with mTOR Inhibitors

Directory of Open Access Journals (Sweden)

Gianluigi Zaza

2013-01-01

Full Text Available The mammalian target of rapamycin inhibitors (mTOR-I, sirolimus and everolimus, are immunosuppressive drugs largely used in renal transplantation. The main mechanism of action of these drugs is the inhibition of the mammalian target of rapamycin (mTOR, a regulatory protein kinase involved in lymphocyte proliferation. Additionally, the inhibition of the crosstalk among mTORC1, mTORC2, and PI3K confers the antineoplastic activities of these drugs. Because of their specific pharmacological characteristics and their relative lack of nephrotoxicity, these inhibitors are valid option to calcineurine inhibitors (CNIs for maintenance immunosuppression in renal transplant recipients with chronic allograft nephropathy. However, as other immunosuppressive drugs, mTOR-I may induce the development of several adverse effects that need to be early recognized and treated to avoid severe illness in renal transplant patients. In particular, mTOR-I may induce systemic nonnephrological side effects including pulmonary toxicity, hematological disorders, dysmetabolism, lymphedema, stomatitis, cutaneous adverse effects, and fertility/gonadic toxicity. Although most of the adverse effects are dose related, it is extremely important for clinicians to early recognize them in order to reduce dosage or discontinue mTOR-I treatment avoiding the onset and development of severe clinical complications.

Collaborative Research between Malaysian and Australian Universities on Learning Analytics: Challenges and Strategies

OpenAIRE

Z. Tasir; S. N. Kew; D. West; Z. Abdullah; D. Toohey

2016-01-01

Research on Learning Analytics is progressively developing in the higher education field by concentrating on the process of students' learning. Therefore, a research project between Malaysian and Australian Universities was initiated in 2015 to look at the use of Learning Analytics to support the development of teaching practice. The focal point of this article is to discuss and share the experiences of Malaysian and Australian universities in the process of developing the collaborative resea...

Malaysian Nuclear Agency: Annual report 2008

International Nuclear Information System (INIS)

2008-01-01

The establishment of Malaysian Nuclear Agency (Nuclear Malaysia) was mooted from idea of the then Malaysia's Deputy Prime Minister, Tun Dr. Ismail Dato Abdul Rahman, that Malaysia should play a role in the development of nuclear science and technology for peaceful purposes. The Centre for Application of Nuclear Energy (CRANE) was the entity to mark the of Malaysia's nuclear programme, focussing on manpower development for a nuclear power programme to provide an option for energy source, following the worldwide oil crisis of the early 1970s. The Cabinet officially approved the establishment of the Tun Ismail Atomic Research Centre (PUSPATI), under the Ministry of Science, Technology and the environment on 19 September 1972. The era of nuclear research in Malaysia began with the historic event signified by the Reaktor TRIGA PUSPATI reaching its first criticality on 28 June 1982. When PUSPATI was placed under the auspices of the Prime Ministers Department, it assumed the name Nuclear Energy Unit (UTN). The Nuclear Energy Unit was later placed under the Minister of Science, Technology and the Environment. In line with the national development, the institute was name Malaysian Institute for Nuclear Technology Research (MINT) on 10 August 1994. To reflect its vision, mission, objectives and activities in the challenging world, a new identity was established, and was officially named as Malaysian Nuclear Agency (Nuclear Malaysia) on 28 September 2006. Nuclear Malaysia, is strategically located nearby the government administration, centre Putrajaya, and Cyberjaya. These annual report highlights all the activities that have been through by the agency in 2008. All the achievements and triumph were highlights in this annual report. It also contained all the agency planning during 2008 to fulfill the objectives, mission and vision to become main players in nuclear research in Malaysia. Finally, there also highlights some publications contribute by all the researchers from

Malaysian Nuclear Agency: Annual report 2009

International Nuclear Information System (INIS)

2009-01-01

The establishment of Malaysian Nuclear Agency (Nuclear Malaysia) was mooted from idea of the then Malaysia's Deputy Prime Minister, Tun Dr. Ismail Dato Abdul Rahman, that Malaysia should play a role in the development of nuclear science and technology for peaceful purposes. The Centre for Application of Nuclear Energy (CRANE) was the entity to mark the of Malaysia's nuclear programme, focussing on manpower development for a nuclear power programme to provide an option for energy source, following the worldwide oil crisis of the early 1970s. The Cabinet officially approved the establishment of the Tun Ismail Atomic Research Centre (PUSPATI), under the Ministry of Science, Technology and the environment on 19 September 1972. The era of nuclear research in Malaysia began with the historic event signified by the Reaktor TRIGA PUSPATI reaching its first criticality on 28 June 1982. When PUSPATI was placed under the auspices of the Prime Ministers Department, it assumed the name Nuclear Energy Unit (UTN). The Nuclear Energy Unit was later placed under the Minister of Science, Technology and the Environment. In line with the national development, the institute was name Malaysian Institute for Nuclear Technology Research (MINT) on 10 August 1994. To reflect its vision, mission, objectives and activities in the challenging world, a new identity was established, and was officially named as Malaysian Nuclear Agency (Nuclear Malaysia) on 28 September 2006. Nuclear Malaysia, is strategically located nearby the government administration, centre Putrajaya, and Cyberjaya. These annual report highlights all the activities that have been through by the agency in 2009. All the achievements and triumph were highlights in this annual report. It also contained all the agency planning during 2009 to fulfill the objectives, mission and vision to become main players in nuclear research in Malaysia. Finally, there also highlights some publications contribute by all the researchers from

Malaysian Nuclear Agency: Annual report 2010

International Nuclear Information System (INIS)

2010-01-01

The establishment of Malaysian Nuclear Agency (Nuclear Malaysia) was mooted from idea of the then Malaysia's Deputy Prime Minister, Tun Dr. Ismail Dato Abdul Rahman, that Malaysia should play a role in the development of nuclear science and technology for peaceful purposes. The Centre for Application of Nuclear Energy (CRANE) was the entity to mark the of Malaysia's nuclear programme, focussing on manpower development for a nuclear power programme to provide an option for energy source, following the worldwide oil crisis of the early 1970s. The Cabinet officially approved the establishment of the Tun Ismail Atomic Research Centre (PUSPATI), under the Ministry of Science, Technology and the environment on 19 September 1972. The era of nuclear research in Malaysia began with the historic event signified by the Reaktor TRIGA PUSPATI reaching its first criticality on 28 June 1982. When PUSPATI was placed under the auspices of the Prime Ministers Department, it assumed the name Nuclear Energy Unit (UTN). The Nuclear Energy Unit was later placed under the Minister of Science, Technology and the Environment. In line with the national development, the institute was name Malaysian Institute for Nuclear Technology Research (MINT) on 10 August 1994. To reflect its vision, mission, objectives and activities in the challenging world, a new identity was established, and was officially named as Malaysian Nuclear Agency (Nuclear Malaysia) on 28 September 2006. Nuclear Malaysia, is strategically located nearby the government administration, centre Putrajaya, and Cyberjaya. These annual report highlights all the activities that have been through by the agency in 2010. All the achievements and triumph were highlights in this annual report. It also contained all the agency planning during 2010 to fulfill the objectives, mission and vision to become main players in nuclear research in Malaysia. Finally, there also highlights some publications contribute by all the researchers from

Malaysian Nuclear Agency; Annual report 2013

International Nuclear Information System (INIS)

2013-01-01

The establishment of Malaysian Nuclear Agency (Nuclear Malaysia) was mooted from idea of the then Malaysia's Deputy Prime Minister, Tun Dr. Ismail Dato Abdul Rahman, that Malaysia should play a role in the development of nuclear science and technology for peaceful purposes. The Centre for Application of Nuclear Energy (CRANE) was the entity to mark the of Malaysia's nuclear programme, focussing on manpower development for a nuclear power programme to provide an option for energy source, following the worldwide oil crisis of the early 1970s. The Cabinet officially approved the establishment of the Tun Ismail Atomic Research Centre (PUSPATI), under the Ministry of Science, Technology and the environment on 19 September 1972. The era of nuclear research in Malaysia began with the historic event signified by the Reaktor TRIGA PUSPATI reaching its first criticality on 28 June 1982. When PUSPATI was placed under the auspices of the Prime Ministers Department, it assumed the name Nuclear Energy Unit (UTN). The Nuclear Energy Unit was later placed under the Minister of Science, Technology and the Environment. In line with the national development, the institute was name Malaysian Institute for Nuclear Technology Research (MINT) on 10 August 1994. To reflect its vision, mission, objectives and activities in the challenging world, a new identity was established, and was officially named as Malaysian Nuclear Agency (Nuclear Malaysia) on 28 September 2006. Nuclear Malaysia, is strategically located nearby the government administration, centre Putrajaya, and Cyberjaya. These annual report highlights all the activities that have been through by the agency in 2013. All the achievements and triumph were highlights in this annual report. It also contained all the agency planning during 2013 to fulfill the objectives, mission and vision to become main players in nuclear research in Malaysia. Finally, there also highlights some publications contribute by all the researchers

Malaysian Nuclear Agency; Annual report 2014

International Nuclear Information System (INIS)

2009-01-01

The establishment of Malaysian Nuclear Agency (Nuclear Malaysia) was mooted from idea of the then Malaysia's Deputy Prime Minister, Tun Dr. Ismail Dato Abdul Rahman, that Malaysia should play a role in the development of nuclear science and technology for peaceful purposes. The Centre for Application of Nuclear Energy (CRANE) was the entity to mark the of Malaysia's nuclear programme, focussing on manpower development for a nuclear power programme to provide an option for energy source, following the worldwide oil crisis of the early 1970s. The Cabinet officially approved the establishment of the Tun Ismail Atomic Research Centre (PUSPATI), under the Ministry of Science, Technology and the environment on 19 September 1972. The era of nuclear research in Malaysia began with the historic event signified by the Reaktor TRIGA PUSPATI reaching its first criticality on 28 June 1982. When PUSPATI was placed under the auspices of the Prime Ministers Department, it assumed the name Nuclear Energy Unit (UTN). The Nuclear Energy Unit was later placed under the Minister of Science, Technology and the Environment. In line with the national development, the institute was name Malaysian Institute for Nuclear Technology Research (MINT) on 10 August 1994. To reflect its vision, mission, objectives and activities in the challenging world, a new identity was established, and was officially named as Malaysian Nuclear Agency (Nuclear Malaysia) on 28 September 2006. Nuclear Malaysia, is strategically located nearby the government administration, centre Putrajaya, and Cyberjaya. These annual report highlights all the activities that have been through by the agency in 2014. All the achievements and triumph were highlights in this annual report. It also contained all the agency planning during 2014 to fulfill the objectives, mission and vision to become main players in nuclear research in Malaysia. Finally, there also highlights some publications contribute by all the researchers

Malaysian Nuclear Agency; Annual report 2011

International Nuclear Information System (INIS)

2008-01-01

The establishment of Malaysian Nuclear Agency (Nuclear Malaysia) was mooted from idea of the then Malaysia's Deputy Prime Minister, Tun Dr. Ismail Dato Abdul Rahman, that Malaysia should play a role in the development of nuclear science and technology for peaceful purposes. The Centre for Application of Nuclear Energy (CRANE) was the entity to mark the of Malaysia's nuclear programme, focussing on manpower development for a nuclear power programme to provide an option for energy source, following the worldwide oil crisis of the early 1970s. The Cabinet officially approved the establishment of the Tun Ismail Atomic Research Centre (PUSPATI), under the Ministry of Science, Technology and the environment on 19 September 1972. The era of nuclear research in Malaysia began with the historic event signified by the Reaktor TRIGA PUSPATI reaching its first criticality on 28 June 1982. When PUSPATI was placed under the auspices of the Prime Ministers Department, it assumed the name Nuclear Energy Unit (UTN). The Nuclear Energy Unit was later placed under the Minister of Science, Technology and the Environment. In line with the national development, the institute was name Malaysian Institute for Nuclear Technology Research (MINT) on 10 August 1994. To reflect its vision, mission, objectives and activities in the challenging world, a new identity was established, and was officially named as Malaysian Nuclear Agency (Nuclear Malaysia) on 28 September 2006. Nuclear Malaysia, is strategically located nearby the government administration, centre Putrajaya, and Cyberjaya. These annual report highlights all the activities that have been through by the agency in 2011. All the achievements and triumph were highlights in this annual report. It also contained all the agency planning during 2011 to fulfill the objectives, mission and vision to become main players in nuclear research in Malaysia. Finally, there also highlights some publications contribute by all the researchers from

Conjunctions in Malaysian Secondary School English Language Textbooks

Directory of Open Access Journals (Sweden)

Alicia Philip

2012-05-01

Full Text Available The present research aims to investigate the distribution pattern of conjunctions and their ranking in two different corpora, namely the Malaysian school English language Textbook Corpus (Textbook Corpus and the British National Corpus (BNC. An additional objective of the study was to find out how conjunctions had been presented in the Malaysian school English language textbooks (Forms 1-5. The method applied was qualitative content analysis. The findings indicated that coordinating conjunctions were the most frequent conjunctions that occurred in the five textbooks followed by subordinating and correlative conjunctions. The ranking of the different types of conjunctions in the Textbook Corpus was similar to that of the reference corpus, BNC. The results also indicated that the textbooks failed to present conjunctions effectively. The findings are expected to help textbook developers or language teachers in developing or adapting learning materials. Keywords: Conjunctions, Textbook evaluation, Distribution patterns

Tracking of Radioactive Sources in Malaysian Nuclear Agency

International Nuclear Information System (INIS)

Mohd Fazlie Abdul Rashid; Noor Fadilla Ismail; Khairuddin Mohamad Kontol; Hairul Nizam Idris; Azimawati Ahmad; Suzilawati Muhd Sarowi; Raymond, Y.T.L.

2014-01-01

Radioactive materials are used in Malaysian Nuclear Agency for various purposes such as research and development, calibration, tracer and irradiation. Inventory of radioactive materials is crucial for ensuring the security and control of all radioactive materials owned and used so as not to be lost or fall into the hands of people who do not have permission to possess or use it. Experience in many countries around the world proves that the improper inventory of radioactive material would lead to loss of control of radioactive materials and will eventually cause an accident of radiation exposure. Radioactive material database has been developed for the need to ensure traceability of radioactive materials in Malaysian Nuclear Agency. Records of radioactive materials are regularly updated based on the classification of the type of radionuclide, the total distribution in each building and the initial activity of radioactive sources. (author)

Dosimetry audits and intercomparisons in radiotherapy: A Malaysian profile

International Nuclear Information System (INIS)

Noor, Noramaliza M.; Nisbet, A.; Hussein, M.; Chu S, Sarene; Kadni, T.; Abdullah, N.; Bradley, D.A.

2017-01-01

Quality audits and intercomparisons are important in ensuring control of processes in any system of endeavour. Present interest is in control of dosimetry in teletherapy, there being a need to assess the extent to which there is consistent radiation dose delivery to the patient. In this study we review significant factors that impact upon radiotherapy dosimetry, focusing upon the example situation of radiotherapy delivery in Malaysia, examining existing literature in support of such efforts. A number of recommendations are made to provide for increased quality assurance and control. In addition to this study, the first level of intercomparison audit i.e. measuring beam output under reference conditions at eight selected Malaysian radiotherapy centres is checked; use being made of 9 µm core diameter Ge-doped silica fibres (Ge-9 µm). The results of Malaysian Secondary Standard Dosimetry Laboratory (SSDL) participation in the IAEA/WHO TLD postal dose audit services during the period between 2011 and 2015 will also been discussed. In conclusion, following review of the development of dosimetry audits and the conduct of one such exercise in Malaysia, it is apparent that regular periodic radiotherapy audits and intercomparison programmes should be strongly supported and implemented worldwide. The programmes to-date demonstrate these to be a good indicator of errors and of consistency between centres. A total of ei+ght beams have been checked in eight Malaysian radiotherapy centres. One out of the eight beams checked produced an unacceptable deviation; this was found to be due to unfamiliarity with the irradiation procedures. Prior to a repeat measurement, the mean ratio of measured to quoted dose was found to be 0.99 with standard deviation of 3%. Subsequent to the repeat measurement, the mean distribution was 1.00, and the standard deviation was 1.3%. - Highlights: • We review significant factors that impact upon radiotherapy dosimetry, • We carried out the

Simulátor 3D tiskárny

OpenAIRE

Čillo, Vladimír

2015-01-01

Tato bakalářská práce se zabýva návrhem a implementací simulátoru 3D tiskárny v jazyce C++ s využitím knihovny Qt. Simulátor předpokládá tiskárnu založenou na nejrozšířenější metodě 3D tisku - Fused Deposition Modeling. Vstupem simulátoru je 3D model ve formátu STL. Pro daný 3D model simulátor poskytuje odhad celkové doby tisku. Součástí simulace je také vizualizace procesu 3D tisku. Výsledkem práce je přenositelný program testovaný pod operačními systémy Linux a Windows. Funkčnost simulátoru...

Brassinosteriod Insensitive 2 (BIN2) acts as a downstream effector of the Target of Rapamycin (TOR) signaling pathway to regulate photoautotrophic growth in Arabidopsis.

Science.gov (United States)

Xiong, Fangjie; Zhang, Rui; Meng, Zhigang; Deng, Kexuan; Que, Yumei; Zhuo, Fengping; Feng, Li; Guo, Sundui; Datla, Raju; Ren, Maozhi

2017-01-01

The components of the target of rapamycin (TOR) signaling pathway have been well characterized in heterotrophic organisms from yeast to humans. However, because of rapamycin insensitivity, embryonic lethality in tor null mutants and a lack of reliable ways of detecting TOR protein kinase in higher plants, the key players upstream and downstream of TOR remain largely unknown in plants. Using engineered rapamycin-sensitive Binding Protein 12-2 (BP12-2) plants, the present study showed that combined treatment with rapamycin and active-site TOR inhibitors (asTORis) results in synergistic inhibition of TOR activity and plant growth in Arabidopsis. Based on this system, we revealed that TOR signaling plays a crucial role in modulating the transition from heterotrophic to photoautotrophic growth in Arabidopsis. Ribosomal protein S6 kinase 2 (S6K2) was identified as a direct downstream target of TOR, and the growth of TOR-suppressed plants could be rescued by up-regulating S6K2. Systems, genetic, and biochemical analyses revealed that Brassinosteriod Insensitive 2 (BIN2) acts as a novel downstream effector of S6K2, and the phosphorylation of BIN2 depends on TOR-S6K2 signaling in Arabidopsis. By combining pharmacological with genetic and biochemical approaches, we determined that the TOR-S6K2-BIN2 signaling pathway plays important roles in regulating the photoautotrophic growth of Arabidopsis. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

Fingerprinting Keywords in Search Queries over Tor

Directory of Open Access Journals (Sweden)

Oh Se Eun

2017-10-01

Full Text Available Search engine queries contain a great deal of private and potentially compromising information about users. One technique to prevent search engines from identifying the source of a query, and Internet service providers (ISPs from identifying the contents of queries is to query the search engine over an anonymous network such as Tor.

Metformin-induced protection against oxidative stress is associated with AKT/mTOR restoration in PC12 cells.

Science.gov (United States)

Khallaghi, Behzad; Safarian, Fatemeh; Nasoohi, Sanaz; Ahmadiani, Abolhassan; Dargahi, Leila

2016-03-01

Reactive oxygen species have been recognized to impair cell function through suppressing Akt the well-known pro-survival molecule. Pile of concrete evidence imply metformin as an Insulin sensitizer may enhance Akt/mTOR activity however the significance of Akt/mTOR recruitment has not yet been revealed in metformin induced neuroprotection against oxidative stress. In the current study using H2O2 induced injury in PC12 cells; we first examined metformin impact on cell death by MTT assay and visual assessment. Metformin pretreated cells were then subjected to immunoblotting as well as real time PCR to find PI3K, Akt, mTOR and S6K concurrent transcriptional and post-transcriptional changes. The proportions of phosphorylated to non-phosphorylated constituents of PI3K/Akt/mTOR/S6K were determined to address their activation upon metformin treatment. According to cells morphology and MTT data metformin led to significant protection against H2O2 induced injury in 0.1 and 0.5mM concentrations. Metformin induced protection concurred with elevated PI3K/Akt/mTOR/S6K activity as well as enhanced GSH levels. These changes paralleled with a profound decline in the corresponding transcripts as determined by real time PCR. Taken together our experimentation supports the hypothesis that Akt/mTOR/S6K cascade may contribute to metformin alleviating effect. The present work while highlighting metformin anti-oxidant characteristics, concludes that Akt/mTOR signaling might be central to the drug's alleviating effects. Copyright © 2016 Elsevier Inc. All rights reserved.

Spirituality Moderates Hopelessness, Depression, and Suicidal Behavior among Malaysian Adolescents.

Science.gov (United States)

Talib, Mansor Abu; Abdollahi, Abbas

2017-06-01

Suicide is an important public health problem for adolescents, and it is essential to increase our knowledge concerning the etiology of suicide among adolescent students. Therefore, this study was designed to examine the associations between hopelessness, depression, spirituality, and suicidal behavior, and to examine spirituality as a moderator between hopelessness, depression, and suicidal behavior among 1376 Malaysian adolescent students. The participants completed measures of depression, hopelessness, daily spiritual experience, and suicidal behavior. Structural equation modeling indicated that adolescent students high in hopelessness and depression, but also high in spirituality, had less suicidal behavior than others. These findings reinforce the importance of spirituality as a protective factor against hopelessness, depression, and suicidal behavior among Malaysian adolescent students.

Foreign Nationals as Offenders and Victims in Malaysian Crime News

Directory of Open Access Journals (Sweden)

Misman Norealyna

2017-01-01

Full Text Available Foreign nationals in Malaysia come from all corners of the world. They are here as migrant labour, highly skilled and professional migrants (expatriates, illegal migrants, refugees, asylum-seekers (Burmese asylum seekers with UNHCR card, forced migrants (human trafficking victims, students, and tourists. The influx of foreign nationals residing in Malaysia coincides with greater number of crime news featuring foreign nationals. This study explores the social construction of foreign nationals as the ‘other’ in the local crime news published by Malaysian newspapers. 94 news headlines and lead sentences of local crime news involving foreign nationals were identified and analysed for this study. Findings suggest that Malaysian newspapers magnify foreign nationals’ migration status in each crime news.

Genetic association of SNPs in the FTO gene and predisposition to obesity in Malaysian Malays

International Nuclear Information System (INIS)

Apalasamy, Y.D.; Ming, M.F.; Rampal, S.; Bulgiba, A.; Mohamed, Z.

2012-01-01

The common variants in the fat mass- and obesity-associated (FTO) gene have been previously found to be associated with obesity in various adult populations. The objective of the present study was to investigate whether the single nucleotide polymorphisms (SNPs) and linkage disequilibrium (LD) blocks in various regions of the FTO gene are associated with predisposition to obesity in Malaysian Malays. Thirty-one FTO SNPs were genotyped in 587 (158 obese and 429 non-obese) Malaysian Malay subjects. Obesity traits and lipid profiles were measured and single-marker association testing, LD testing, and haplotype association analysis were performed. LD analysis of the FTO SNPs revealed the presence of 57 regions with complete LD (D' = 1.0). In addition, we detected the association of rs17817288 with low-density lipoprotein cholesterol. The FTO gene may therefore be involved in lipid metabolism in Malaysian Malays. Two haplotype blocks were present in this region of the FTO gene, but no particular haplotype was found to be significantly associated with an increased risk of obesity in Malaysian Malays

Genetic association of SNPs in the FTO gene and predisposition to obesity in Malaysian Malays

Energy Technology Data Exchange (ETDEWEB)

Apalasamy, Y.D. [Pharmacogenomics Laboratory, Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur (Malaysia); Ming, M.F.; Rampal, S.; Bulgiba, A. [Julius Centre University of Malaya, Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur (Malaysia); Mohamed, Z. [Pharmacogenomics Laboratory, Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur (Malaysia)

2012-08-24

The common variants in the fat mass- and obesity-associated (FTO) gene have been previously found to be associated with obesity in various adult populations. The objective of the present study was to investigate whether the single nucleotide polymorphisms (SNPs) and linkage disequilibrium (LD) blocks in various regions of the FTO gene are associated with predisposition to obesity in Malaysian Malays. Thirty-one FTO SNPs were genotyped in 587 (158 obese and 429 non-obese) Malaysian Malay subjects. Obesity traits and lipid profiles were measured and single-marker association testing, LD testing, and haplotype association analysis were performed. LD analysis of the FTO SNPs revealed the presence of 57 regions with complete LD (D' = 1.0). In addition, we detected the association of rs17817288 with low-density lipoprotein cholesterol. The FTO gene may therefore be involved in lipid metabolism in Malaysian Malays. Two haplotype blocks were present in this region of the FTO gene, but no particular haplotype was found to be significantly associated with an increased risk of obesity in Malaysian Malays.

Genetic association of SNPs in the FTO gene and predisposition to obesity in Malaysian Malays

Directory of Open Access Journals (Sweden)

Y.D. Apalasamy

2012-12-01

Full Text Available The common variants in the fat mass- and obesity-associated (FTO gene have been previously found to be associated with obesity in various adult populations. The objective of the present study was to investigate whether the single nucleotide polymorphisms (SNPs and linkage disequilibrium (LD blocks in various regions of the FTO gene are associated with predisposition to obesity in Malaysian Malays. Thirty-one FTO SNPs were genotyped in 587 (158 obese and 429 non-obese Malaysian Malay subjects. Obesity traits and lipid profiles were measured and single-marker association testing, LD testing, and haplotype association analysis were performed. LD analysis of the FTO SNPs revealed the presence of 57 regions with complete LD (D’ = 1.0. In addition, we detected the association of rs17817288 with low-density lipoprotein cholesterol. The FTO gene may therefore be involved in lipid metabolism in Malaysian Malays. Two haplotype blocks were present in this region of the FTO gene, but no particular haplotype was found to be significantly associated with an increased risk of obesity in Malaysian Malays.

Eclectic Model in the Malaysian Education System

Science.gov (United States)

Othman, Nooraini; Mohamad, Khairul Azmi; Ilmuwan, Yayasan

2011-01-01

The present work aims at analysing the adoption of eclectic model in the Malaysian education system. The analysis is specifically looked from the angle of Islam and the Muslims. Malaysia has a long history of education system developments, from pre to post independence of the country. From what was initially traditional, modernity later came to…

Expression profiling and functional analysis reveals that TOR is a key player in regulating photosynthesis and phytohormone signaling pathways in Arabidopsis.

Science.gov (United States)

Dong, Pan; Xiong, Fangjie; Que, Yumei; Wang, Kai; Yu, Lihua; Li, Zhengguo; Ren, Maozhi

2015-01-01

Target of rapamycin (TOR) acts as a master regulator to control cell growth by integrating nutrient, energy, and growth factors in all eukaryotic species. TOR plays an evolutionarily conserved role in regulating the transcription of genes associated with anabolic and catabolic processes in Arabidopsis, but little is known about the functions of TOR in photosynthesis and phytohormone signaling, which are unique features of plants. In this study, AZD8055 (AZD) was screened as the strongest active-site TOR inhibitor (asTORi) in Arabidopsis compared with TORIN1 and KU63794 (KU). Gene expression profiles were evaluated using RNA-seq after treating Arabidopsis seedlings with AZD. More than three-fold differentially expressed genes (DEGs) were identified in AZD-treated plants relative to rapamycin-treated plants in previous studies. Most of the DEGs and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways involved in cell wall elongation, ribosome biogenesis, and cell autophagy were common to both AZD- and rapamycin-treated samples, but AZD displayed much broader and more efficient inhibition of TOR compared with rapamycin. Importantly, the suppression of TOR by AZD resulted in remodeling of the expression profile of the genes associated with photosynthesis and various phytohormones, indicating that TOR plays a crucial role in modulating photosynthesis and phytohormone signaling in Arabidopsis. These newly identified DEGs expand the understanding of TOR signaling in plants. This study elucidates the novel functions of TOR in photosynthesis and phytohormone signaling and provides a platform to study the downstream targets of TOR in Arabidopsis.

Caloric restriction protects against electrical kindling of the amygdala by inhibiting the mTOR signaling pathway

Directory of Open Access Journals (Sweden)

Bryan Victor Phillips-Farfan

2015-03-01

Full Text Available Caloric restriction (CR has been shown to possess antiepileptic properties; however its mechanism of action is poorly understood. CR might inhibit the activity of the mammalian or mechanistic target of rapamycin (mTOR signaling cascade, which seems to participate crucially in the generation of epilepsy. Thus, we investigated the effect of CR on the mTOR pathway and whether CR modified epilepsy generation due to electrical amygdala kindling. The former was studied by analyzing the phosphorylation of adenosine monophosphate-activated protein kinase, protein kinase B and the ribosomal protein S6. The mTOR cascade is regulated by energy and by insulin levels, both of which may be changed by CR; thus we investigated if CR altered the levels of energy substrates in the blood or the level of insulin in plasma. Finally, we studied if CR modified the expression of genes that encode proteins participating in the mTOR pathway. CR increased the after-discharge threshold and tended to reduce the after-discharge duration, indicating an anti-convulsive action. CR diminished the phosphorylation of protein kinase B and ribosomal protein S6, suggesting an inhibition of the mTOR cascade. However, CR did not change glucose, β-hydroxybutyrate or insulin levels; thus the effects of CR were independent from them. Interestingly, CR also did not modify the expression of any investigated gene. The results suggest that the anti-epileptic effect of CR may be partly due to inhibition of the mTOR pathway.

Ribosomal protein S6 phosphorylation is controlled by TOR and modulated by PKA in Candida albicans.

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Chowdhury, Tahmeena; Köhler, Julia R

2015-10-01

TOR and PKA signaling pathways control eukaryotic cell growth and proliferation. TOR activity in model fungi, such as Saccharomyces cerevisiae, responds principally to nutrients, e.g., nitrogen and phosphate sources, which are incorporated into the growing cell mass; PKA signaling responds to the availability of the cells' major energy source, glucose. In the fungal commensal and pathogen, Candida albicans, little is known of how these pathways interact. Here, the signal from phosphorylated ribosomal protein S6 (P-S6) was defined as a surrogate marker for TOR-dependent anabolic activity in C. albicans. Nutritional, pharmacologic and genetic modulation of TOR activity elicited corresponding changes in P-S6 levels. The P-S6 signal corresponded to translational activity of a GFP reporter protein. Contributions of four PKA pathway components to anabolic activation were then examined. In high glucose concentrations, only Tpk2 was required to upregulate P-S6 to physiologic levels, whereas all four tested components were required to downregulate P-S6 in low glucose. TOR was epistatic to PKA components with respect to P-S6. In many host niches inhabited by C. albicans, glucose is scarce, with protein being available as a nitrogen source. We speculate that PKA may modulate TOR-dependent cell growth to a rate sustainable by available energy sources, when monomers of anabolic processes, such as amino acids, are abundant. © 2015 John Wiley & Sons Ltd.

The role of mTOR signaling in the regulation of protein synthesis and muscle mass during immobilization in mice

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You, Jae-Sung; Anderson, Garrett B.; Dooley, Matthew S.; Hornberger, Troy A.

2015-01-01

ABSTRACT The maintenance of skeletal muscle mass contributes substantially to health and to issues associated with the quality of life. It has been well recognized that skeletal muscle mass is regulated by mechanically induced changes in protein synthesis, and that signaling by mTOR is necessary for an increase in protein synthesis and the hypertrophy that occurs in response to increased mechanical loading. However, the role of mTOR signaling in the regulation of protein synthesis and muscle mass during decreased mechanical loading remains largely undefined. In order to define the role of mTOR signaling, we employed a mouse model of hindlimb immobilization along with pharmacological, mechanical and genetic means to modulate mTOR signaling. The results first showed that immobilization induced a decrease in the global rates of protein synthesis and muscle mass. Interestingly, immobilization also induced an increase in mTOR signaling, eIF4F complex formation and cap-dependent translation. Blocking mTOR signaling during immobilization with rapamycin not only impaired the increase in eIF4F complex formation, but also augmented the decreases in global protein synthesis and muscle mass. On the other hand, stimulating immobilized muscles with isometric contractions enhanced mTOR signaling and rescued the immobilization-induced decrease in global protein synthesis through a rapamycin-sensitive mechanism that was independent of ribosome biogenesis. Unexpectedly, the effects of isometric contractions were also independent of eIF4F complex formation. Similar to isometric contractions, overexpression of Rheb in immobilized muscles enhanced mTOR signaling, cap-dependent translation and global protein synthesis, and prevented the reduction in fiber size. Therefore, we conclude that the activation of mTOR signaling is both necessary and sufficient to alleviate the decreases in protein synthesis and muscle mass that occur during immobilization. Furthermore, these results indicate

A kinase-dead knock-in mutation in mTOR leads to early embryonic lethality and is dispensable for the immune system in heterozygous mice

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Cavender Druie

2009-05-01

Full Text Available Abstract Background The mammalian target of rapamycin protein (mTOR is an evolutionarily conserved kinase that regulates protein synthesis, cell cycle progression and proliferation in response to various environmental cues. As a critical downstream mediator of PI3K signaling, mTOR is important for lymphocyte development and function of mature T and B-cells. Most studies of mTOR in immune responses have relied on the use of pharmacological inhibitors, such as rapamycin. Rapamycin-FKBP12 complex exerts its immunosuppressive and anti-proliferative effect by binding outside the kinase domain of mTOR, and subsequently inhibiting downstream mTOR signaling. Results To determine the requirement for mTOR kinase activity in the immune system function, we generated knock-in mice carrying a mutation (D2338 in the catalytic domain of mTOR. While homozygous mTOR kd/kd embryos died before embryonic day 6.5, heterozygous mTOR+/kd mice appeared entirely normal and are fertile. mTOR +/kd mice exhibited normal T and B cell development and unaltered proliferative responses of splenocytes to IL-2 and TCR/CD28. In addition, heterozygousity for the mTOR kinase-dead allele did not sensitize T cells to rapamycin in a CD3-mediated proliferation assay. Unexpectedly, mTOR kinase activity towards its substrate 4E-BP1 was not decreased in hearts and livers from heterozygous animals. Conclusion Altogether, our findings indicate that mTOR kinase activity is indispensable for the early development of mouse embryos. Moreover, a single wild type mTOR allele is sufficient to maintain normal postnatal growth and lymphocyte development and proliferation.

Collaborative and Cooperative Learning in Malaysian Mathematics Education

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Hossain, Md. Anowar; Tarmizi, Rohani Ahmad; Ayud, Ahmad Fauzi Mohd

2012-01-01

Collaborative and cooperative learning studies are well recognized in Malaysian mathematics education research. Cooperative learning is used to serve various ability students taking into consideration of their level of understanding, learning styles, sociological backgrounds that develop students' academic achievement and skills, and breeze the…

Oral health quality-of-life among undergraduate Malaysian dental students.

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Harsh, P; Arunima, C; Manoj, K

2012-06-01

To assess the oral health quality of life among Malaysian dental students using the Oral Impacts on Daily Performance (OIDP) scale. Malaysian dental students of Melaka Manipal Medical College, Manipal campus, Manipal University, Manipal answered a structured questionnaire recording the demographic characteristics, behavioral characteristics and eight items of OIDP. The mean OIDP ADD and OIDP SC scores were respectively, 4.10 (sd = 5.16, range 8 - 40) and 2. 3 (sd = 2.3, range 0-8). A total of 50%, 32.9% and 28.6% of the dental students confirmed difficulties with eating, cleaning teeth and sleeping and relaxing, respectively. Statistically significant relationships were observed between OIDP (ultimate oral impact) and a count of non-clinical oral health indicators representing the second (intermediate) levels of oral impact. Logistic regression analysis revealed that dental students who were dissatisfied with their oral health had greater oral impact than their counterparts. The odds ratios for satisfaction with oral health, dental visits and frequency of brushing teeth were respectively 1.74 (0.58-5.32), 0.59 (0.11-3.24) and 1.33 (0.41-4.30). The study reports the Oral Impact on Daily Performance among Malaysian dental students and provides evidence of importance of social and behavioral characteristics in shaping dental students response.

Regression of cardiac growth in kidney transplant recipients using anti-m-TOR drugs plus RAS blockers: a controlled longitudinal study.

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Hernández, Domingo; Ruiz-Esteban, Pedro; Gaitán, Daniel; Burgos, Dolores; Mazuecos, Auxiliadora; Collantes, Rocío; Briceño, Eva; Palma, Eulalia; Cabello, Mercedes; González-Molina, Miguel; De Mora, Manuel

2014-04-23

Left ventricular hypertrophy (LVH) is common in kidney transplant (KT) recipients. LVH is associated with a worse outcome, though m-TOR therapy may help to revert this complication. We therefore conducted a longitudinal study to assess morphological and functional echocardiographic changes after conversion from CNI to m-TOR inhibitor drugs in nondiabetic KT patients who had previously received RAS blockers during the follow-up. We undertook a 1-year nonrandomized controlled study in 30 non-diabetic KT patients who were converted from calcineurin inhibitor (CNI) to m-TOR therapy. A control group received immunosuppressive therapy based on CNIs. Two echocardiograms were done during the follow-up. Nineteen patients were switched to SRL and 11 to EVL. The m-TOR group showed a significant reduction in LVMi after 1 year (from 62 ± 22 to 55 ± 20 g/m2.7; P=0.003, paired t-test). A higher proportion of patients showing LVMi reduction was observed in the m-TOR group (53.3 versus 29.3%, P=0.048) at the study end. In addition, only 56% of the m-TOR patients had LVH at the study end compared to 77% of the control group (P=0.047). A significant change from baseline in deceleration time in early diastole was observed in the m-TOR group compared with the control group (P=0.019). Switching from CNI to m-TOR therapy in non-diabetic KT patients may regress LVH, independently of blood pressure changes and follow-up time. This suggests a direct non-hemodynamic effect of m-TOR drugs on cardiac mass.

mTOR inhibitors alone and in combination with JAK2 inhibitors effectively inhibit cells of myeloproliferative neoplasms.

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Costanza Bogani

Full Text Available BACKGROUND: Dysregulated signaling of the JAK/STAT pathway is a common feature of chronic myeloproliferative neoplasms (MPN, usually associated with JAK2V617F mutation. Recent clinical trials with JAK2 inhibitors showed significant improvements in splenomegaly and constitutional symptoms in patients with myelofibrosis but meaningful molecular responses were not documented. Accordingly, there remains a need for exploring new treatment strategies of MPN. A potential additional target for treatment is represented by the PI3K/AKT/mammalian target of rapamycin (mTOR pathway that has been found constitutively activated in MPN cells; proof-of-evidence of efficacy of the mTOR inhibitor RAD001 has been obtained recently in a Phase I/II trial in patients with myelofibrosis. The aim of the study was to characterize the effects in vitro of mTOR inhibitors, used alone and in combination with JAK2 inhibitors, against MPN cells. FINDINGS: Mouse and human JAK2V617F mutated cell lines and primary hematopoietic progenitors from MPN patients were challenged with an allosteric (RAD001 and an ATP-competitive (PP242 mTOR inhibitor and two JAK2 inhibitors (AZD1480 and ruxolitinib. mTOR inhibitors effectively reduced proliferation and colony formation of cell lines through a slowed cell division mediated by changes in cell cycle transition to the S-phase. mTOR inhibitors also impaired the proliferation and prevented colony formation from MPN hematopoietic progenitors at doses significantly lower than healthy controls. JAK2 inhibitors produced similar antiproliferative effects in MPN cell lines and primary cells but were more potent inducers of apoptosis, as also supported by differential effects on cyclinD1, PIM1 and BcLxL expression levels. Co-treatment of mTOR inhibitor with JAK2 inhibitor resulted in synergistic activity against the proliferation of JAK2V617F mutated cell lines and significantly reduced erythropoietin-independent colony growth in patients with

Comparison of CTA and Textual Feedback in Usability Testing for Malaysian Users

DEFF Research Database (Denmark)

Sivaji, Ashok; Clemmensen, Torkil; Nielsen, Søren Feodor

Usability moderators found that the concurrent think-aloud (CTA) method has some cultural limitation that impacts usability testing with Malaysian users. This gives rise to proposing a new method called textual feedback. The research question is to determine whether there are any differences...... in usability defects from the concurrent think-aloud (CTA) method (Condition 2) and textual feedback method (Condition 1) within the same group of Malaysian users. A pair-wise t-test was used, whereby users were subjected to performing usability task using both methods. Results reveal that we can reject...

Reduced AMPK-ACC and mTOR signaling in muscle from older men, and effect of resistance exercise.

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Li, Mengyao; Verdijk, Lex B; Sakamoto, Kei; Ely, Brian; van Loon, Luc J C; Musi, Nicolas

2012-01-01

AMP-activated protein kinase (AMPK) is a key energy-sensitive enzyme that controls numerous metabolic and cellular processes. Mammalian target of rapamycin (mTOR) is another energy/nutrient-sensitive kinase that controls protein synthesis and cell growth. In this study we determined whether older versus younger men have alterations in the AMPK and mTOR pathways in skeletal muscle, and examined the effect of a long term resistance type exercise training program on these signaling intermediaries. Older men had decreased AMPKα2 activity and lower phosphorylation of AMPK and its downstream signaling substrate acetyl-CoA carboxylase (ACC). mTOR phosphylation also was reduced in muscle from older men. Exercise training increased AMPKα1 activity in older men, however, AMPKα2 activity, and the phosphorylation of AMPK, ACC and mTOR, were not affected. In conclusion, older men have alterations in the AMPK-ACC and mTOR pathways in muscle. In addition, prolonged resistance type exercise training induces an isoform-selective up regulation of AMPK activity. Published by Elsevier Ireland Ltd.

Prepositions and ESL Learners: the Malaysian Scenario

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Norwati Roslim

2014-01-01

Full Text Available This article presents a review of the literature on prepositions with a focus on definitions and main difficulties faced by Malaysian students. It further highlights recommendations about the role of syllabus designers, textbook writers and teachers in meeting these challenges. It is hoped that this article could provide a platform for any further studies on prepositions.

TOR and S6K1 promote translation reinitiation of uORF-containing mRNAs via phosphorylation of eIF3h.

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Schepetilnikov, Mikhail; Dimitrova, Maria; Mancera-Martínez, Eder; Geldreich, Angèle; Keller, Mario; Ryabova, Lyubov A

2013-04-17

Mammalian target-of-rapamycin (mTOR) triggers S6 kinase (S6K) activation to phosphorylate targets linked to translation in response to energy, nutrients, and hormones. Pathways of TOR activation in plants remain unknown. Here, we uncover the role of the phytohormone auxin in TOR signalling activation and reinitiation after upstream open reading frame (uORF) translation, which in plants is dependent on translation initiation factor eIF3h. We show that auxin triggers TOR activation followed by S6K1 phosphorylation at T449 and efficient loading of uORF-mRNAs onto polysomes in a manner sensitive to the TOR inhibitor Torin-1. Torin-1 mediates recruitment of inactive S6K1 to polysomes, while auxin triggers S6K1 dissociation and recruitment of activated TOR instead. A putative target of TOR/S6K1-eIF3h-is phosphorylated and detected in polysomes in response to auxin. In TOR-deficient plants, polysomes were prebound by inactive S6K1, and loading of uORF-mRNAs and eIF3h was impaired. Transient expression of eIF3h-S178D in plant protoplasts specifically upregulates uORF-mRNA translation. We propose that TOR functions in polysomes to maintain the active S6K1 (and thus eIF3h) phosphorylation status that is critical for translation reinitiation.

TOR complex 2-Ypk1 signaling is an essential positive regulator of the general amino acid control response and autophagy.

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Vlahakis, Ariadne; Graef, Martin; Nunnari, Jodi; Powers, Ted

2014-07-22

The highly conserved Target of Rapamycin (TOR) kinase is a central regulator of cell growth and metabolism in response to nutrient availability. TOR functions in two structurally and functionally distinct complexes, TOR Complex 1 (TORC1) and TOR Complex 2 (TORC2). Through TORC1, TOR negatively regulates autophagy, a conserved process that functions in quality control and cellular homeostasis and, in this capacity, is part of an adaptive nutrient deprivation response. Here we demonstrate that during amino acid starvation TOR also operates independently as a positive regulator of autophagy through the conserved TORC2 and its downstream target protein kinase, Ypk1. Under these conditions, TORC2-Ypk1 signaling negatively regulates the Ca(2+)/calmodulin-dependent phosphatase, calcineurin, to enable the activation of the amino acid-sensing eIF2α kinase, Gcn2, and to promote autophagy. Our work reveals that the TORC2 pathway regulates autophagy in an opposing manner to TORC1 to provide a tunable response to cellular metabolic status.

Optimising the use of mTOR inhibitors in renal transplantation.

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Russ, Graeme R

2013-11-20

Renal transplantation is the treatment of choice for end-stage renal failure. Although advances in immunosuppression have led to improvements in short-term outcomes, graft survival beyond 5 to 10 years has not improved. One of the major causes of late renal allograft failure is chronic allograft nephropathy, a component of which is nephrotoxicity from the use of calcineurin inhibitors (CNIs). In addition, premature patient death is a major limitation of renal transplantation and the major causes are cancer, cardiovascular disease and infection. CNI-free immunosuppressive regimens based on mammalian target of rapamycin (mTOR) inhibitors have been trial led over the last few years and have defined the rational use of these agents. Conversion from a CNI-based to an mTOR-inhibitor-based regimen has been successful at improving renal function for a number of years after conversion, although long-term survival outcomes are still awaited. The studies suggest that the safest and most effective time to convert is between 1 and 6 months after transplant. In addition, mTOR-inhibitor-based regimens have been shown to be associated with lower rates of post-transplant malignancy and less cytomegalovirus infection, which may add further to the appeal of this approach.

Immunization knowledge and practice among Malaysian parents: a questionnaire development and pilot-testing.

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Awadh, Ammar Ihsan; Hassali, Mohamed Azmi; Al-lela, Omer Qutaiba; Bux, Siti Halimah; Elkalmi, Ramadan M; Hadi, Hazrina

2014-10-27

Parents are the main decision makers for their children vaccinations. This fact makes parents' immunization knowledge and practices as predictor factors for immunization uptake and timeliness. The aim of this pilot study was to develop a reliable and valid instrument in Malaysian language to measure immunization knowledge and practice (KP) of Malaysian parents. A cross-sectional prospective pilot survey was conducted among 88 Malaysian parents who attended public health facilities that provide vaccinations. Translated immunization KP questionnaires (Bahasa Melayu version) were used. Descriptive statistics were applied, face and content validity were assessed, and internal consistency, test-retest reliability, and construct validity were determined. The mean ± standard deviation (SD) of the knowledge scores was 7.36 ± 2.29 and for practice scores was 7.13 ± 2.20. Good internal consistency was found for knowledge and practice items (Cronbach's alpha = 0.757 and 0.743 respectively); the test-retest reliability value was 0.740 (p = 0.014). A panel of three specialist pharmacists who are experts in this field judged the face and content validity of the final questionnaire. Parents with up-to-date immunized children had significantly better knowledge and practice scores than parents who did not (p Malaysian parents and therefore this version can be used in future research.

Antifungal activity of selected Malaysian honeys: a comparison with Manuka honey

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Siti Aisyah Sayadi

2015-07-01

Full Text Available Objective: To evaluate four selected Malaysian honey samples from different floral sources (Gelam, Tualang, Nenas and Acacia for their ability to inhibit the growth of fungi and yeast strains (Candida albicans, Aspergillus niger, Epidermophyton floccosum, Microsporum gypseum, Trichophyton rubrum and Trichophyton mentagrophytes. Methods: The broth microdilution method was used to assess the antifungal activity of honey against yeasts at different concentrations ranging from 0.01% to 70% (v/v. Minimum inhibitory concentration (MIC of the honeys were determined by visual inspection and spectrophotometric assay. Minimum fungicidal concentration test was performed by further sub-culturing from the plates which showed no visible growth in the MIC assay onto Sabroud dextrose agar. Results: All tested Malaysian honeys except Gelam showed antifungal activity against all species analysed, with the MIC ranging from 25% (v/v to 50% (v/v while MIC of Manuka honey ranged between 21% to 53% (v/v. Candida albicans was more susceptible to honey than other species tested. Conclusions: Locally produced honeys exhibited antifungal activity which is less than or equal to that of Manuka honey. Our data showed evidence in support of the therapeutic uses of Malaysian honeys.

Production of Rare Earth Elements from Malaysian Monazite by Selective Precipitation

International Nuclear Information System (INIS)

Che Nor Aniza Che Zainul Bahri; Al- Areqi, W.M.; Amran Abdul Majid; Mohd Izzat Fahmi Mohd Ruf

2016-01-01

Rare earth elements (REEs) are very valuable and have high demands for advanced technology nowadays. REEs can be classified to light rare earth elements (LREEs) and heavy rare earth elements (HREEs). Malaysian rare earth ore especially monazite, is rich with LREEs compared to HREEs. Therefore a study was carried out to extract the REE from Malaysian monazite. The objectives of this study are to determine the content of REEs in Malaysian monazite leach solution, as well as to produce high grade of REEs. Concentrated sulphuric acid was used in digestion process and the filtrate containing the REEs was determined using Inductively Coupled Plasma- Mass Spectrometry (ICP-MS). Ammonia solution was used for REEs precipitation from monazite leach solution. The result indicated that REEs was successfully separated from monazite leach solution through selective precipitation using ammonia at pH 2.34 and the percentage of REEs that successfully separated was 70.03 - 81.85 %. The percentage of REEs which successfully separated from final solution was 96.05 - 99.10 %. Therefore, to have high purification of individual REEs, solvent extraction process should be carried out. (author)

Measuring and explaining multi-directional inefficiency in the Malaysian dairy industry.

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Mohd Suhaimi, Nurul Aisyah Binti; de Mey, Yann; Oude Lansink, Alfons

2017-01-01

The purpose of this paper is to measure the technical inefficiency of dairy farms and subsequently investigate the factors affecting technical inefficiency in the Malaysian dairy industry. This study uses multi-directional efficiency analysis to measure the technical inefficiency scores on a sample of 200 farm observations and single-bootstrap truncated regression model to define factors affecting technical inefficiency. Managerial and program inefficiency scores are presented for intensive and semi-intensive production systems. The results reveal marked differences in the inefficiency scores across inputs and between production systems. Intensive systems generally have lowest managerial and program inefficiency scores in the Malaysian dairy farming sector. Policy makers could use this information to advise dairy farmers to convert their farming system to the intensive system. The results suggest that the Malaysian Government should redefine its policy for providing farm finance and should target young farmers when designing training and extension programs in order to improve the performance of the dairy sector. The existing literature on Southeast Asian dairy farming has neither focused on investigating input-specific efficiency nor on comparing managerial and program efficiency. This paper aims to fill this gap.

mTOR signaling promotes stem cell activation via counterbalancing BMP-mediated suppression during hair regeneration.

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Deng, Zhili; Lei, Xiaohua; Zhang, Xudong; Zhang, Huishan; Liu, Shuang; Chen, Qi; Hu, Huimin; Wang, Xinyue; Ning, Lina; Cao, Yujing; Zhao, Tongbiao; Zhou, Jiaxi; Chen, Ting; Duan, Enkui

2015-02-01

Hair follicles (HFs) undergo cycles of degeneration (catagen), rest (telogen), and regeneration (anagen) phases. Anagen begins when the hair follicle stem cells (HFSCs) obtain sufficient activation cues to overcome suppressive signals, mainly the BMP pathway, from their niche cells. Here, we unveil that mTOR complex 1 (mTORC1) signaling is activated in HFSCs, which coincides with the HFSC activation at the telogen-to-anagen transition. By using both an inducible conditional gene targeting strategy and a pharmacological inhibition method to ablate or inhibit mTOR signaling in adult skin epithelium before anagen initiation, we demonstrate that HFs that cannot respond to mTOR signaling display significantly delayed HFSC activation and extended telogen. Unexpectedly, BMP signaling activity is dramatically prolonged in mTOR signaling-deficient HFs. Through both gain- and loss-of-function studies in vitro, we show that mTORC1 signaling negatively affects BMP signaling, which serves as a main mechanism whereby mTORC1 signaling facilitates HFSC activation. Indeed, in vivo suppression of BMP by its antagonist Noggin rescues the HFSC activation defect in mTORC1-null skin. Our findings reveal a critical role for mTOR signaling in regulating stem cell activation through counterbalancing BMP-mediated repression during hair regeneration. © The Author (2015). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, IBCB, SIBS, CAS. All rights reserved.

Immunohistochemical Investigation of HER/AKT/mTOR Pathway and Cellular Adhesion Molecules in Urothelial Carcinomas

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Nikolaos Koletsas

2017-01-01

Full Text Available Background. Several investigators have suggested the possibility that the expression of both EGFR and HER2 could be utilized for molecularly targeted therapy in urinary bladder cancer. We tried to evaluate the expression of HER2 and EGFR and activation of the AKT/PTEN/mTOR pathway in urothelial carcinomas and if there is any association between them and cellular adhesion molecules (CAMs. Materials and Methods. Forty-one paraffin-embedded urothelial cancer tissue blocks were collected. Immunostains for HER2, EGFR, MIB1, phospho-AKT, PTEN, phospho-mTOR, e-cadherin, p-cadherin, and b-catenin were performed on tissue microarrays sections. The immunohistochemical results were correlated with clinicopathological parameters. Results. The overexpression of HER2 was found in 19.6% of the cases and it was associated with high grade tumors with a high mitotic index and phosphorylation of AKT and mTOR. Muscle-invasive tumors presented both cytoplasmic and nuclear losses of PTEN expression. There was no association between HER/AKT/mTOR pathway activation and CAM expression. Although cadherins were often coexpressed, only p-cadherin immunoreactivity was associated with tumor grade and high proliferative index. Conclusions. HER2 overexpression is found in a respective proportion of urothelial carcinomas. P-cadherin expression is associated with high grade UCs but it is not affected by HER2 overexpression or by activation of HER/AKT/mTOR pathway.

Scaling the Drosophila Wing: TOR-Dependent Target Gene Access by the Hippo Pathway Transducer Yorkie.

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Parker, Joseph; Struhl, Gary

2015-10-01

Organ growth is controlled by patterning signals that operate locally (e.g., Wingless/Ints [Wnts], Bone Morphogenetic Proteins [BMPs], and Hedgehogs [Hhs]) and scaled by nutrient-dependent signals that act systemically (e.g., Insulin-like peptides [ILPs] transduced by the Target of Rapamycin [TOR] pathway). How cells integrate these distinct inputs to generate organs of the appropriate size and shape is largely unknown. The transcriptional coactivator Yorkie (Yki, a YES-Associated Protein, or YAP) acts downstream of patterning morphogens and other tissue-intrinsic signals to promote organ growth. Yki activity is regulated primarily by the Warts/Hippo (Wts/Hpo) tumour suppressor pathway, which impedes nuclear access of Yki by a cytoplasmic tethering mechanism. Here, we show that the TOR pathway regulates Yki by a separate and novel mechanism in the Drosophila wing. Instead of controlling Yki nuclear access, TOR signaling governs Yki action after it reaches the nucleus by allowing it to gain access to its target genes. When TOR activity is inhibited, Yki accumulates in the nucleus but is sequestered from its normal growth-promoting target genes--a phenomenon we term "nuclear seclusion." Hence, we posit that in addition to its well-known role in stimulating cellular metabolism in response to nutrients, TOR also promotes wing growth by liberating Yki from nuclear seclusion, a parallel pathway that we propose contributes to the scaling of wing size with nutrient availability.

Endometriose torácica

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Filipa Costa

2008-05-01

Full Text Available Resumo: A endometriose torácica define-se pela presença de tecido endometrial no pulmão ou pleura e manifesta--se clinicamente por hemoptises cíclicas, pneumotórax ou hemotórax recorrente coincidentes com a menstruação. Tratando-se de uma patologia rara, nem sempre é considerada no diagnóstico diferencial quando se avaliam estas manifestações. Os exames complementares de diagnóstico geralmente não revelam alterações específicas, sendo o diagnóstico feito com base na história clínica. A chave do diagnóstico são os sintomas catameniais, sendo fundamental realizar uma história clínica minuciosa para chegar atempadamente ao diagnóstico correcto. O tratamento hormonal e a cirurgia são as duas alternativas terapêuticas para esta patologia.Os autores descrevem o caso clínico de uma doente de 27 anos que surge com um quadro de hemoptises catameniais. Os exames complementares de diagnóstico realizados foram inconclusivos. Baseado na história clínica, assumiu-se o diagnóstico de endometriose pulmonar e iniciou-se tratamento com contraceptivos orais com resolução total dos sintomas.A propósito do caso clínico, os autores fazem uma revisão das principais manifestações clínicas, da patogénese, do diagnóstico e do tratamento da endometriose torácica. Abstract: Thoracic endometriosis is defined by the presence of endometrial tissue in the lungs or pleura, and is characterised by cyclic hemoptysis or recurrent hemothorax or pneumothorax occurring with the menstruation. Being a rare clinical entity, it is not always considered in the differential diagnosis when these symptoms are evaluated. The exams performed during the diagnostic work-up frequently show nonspecific alterations, however a presumptive diagnosis can be made based on the typical clinical history. The key to the diagnosis are the catamenial symptoms, so a thorough clinical history is essential to promptly reach the correct diagnosis. Hormonal treatment and

Predicting ambient aerosol thermal-optical reflectance (TOR) measurements from infrared spectra: organic carbon

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Dillner, A. M.; Takahama, S.

2015-03-01

Organic carbon (OC) can constitute 50% or more of the mass of atmospheric particulate matter. Typically, organic carbon is measured from a quartz fiber filter that has been exposed to a volume of ambient air and analyzed using thermal methods such as thermal-optical reflectance (TOR). Here, methods are presented that show the feasibility of using Fourier transform infrared (FT-IR) absorbance spectra from polytetrafluoroethylene (PTFE or Teflon) filters to accurately predict TOR OC. This work marks an initial step in proposing a method that can reduce the operating costs of large air quality monitoring networks with an inexpensive, non-destructive analysis technique using routinely collected PTFE filter samples which, in addition to OC concentrations, can concurrently provide information regarding the composition of organic aerosol. This feasibility study suggests that the minimum detection limit and errors (or uncertainty) of FT-IR predictions are on par with TOR OC such that evaluation of long-term trends and epidemiological studies would not be significantly impacted. To develop and test the method, FT-IR absorbance spectra are obtained from 794 samples from seven Interagency Monitoring of PROtected Visual Environment (IMPROVE) sites collected during 2011. Partial least-squares regression is used to calibrate sample FT-IR absorbance spectra to TOR OC. The FTIR spectra are divided into calibration and test sets by sampling site and date. The calibration produces precise and accurate TOR OC predictions of the test set samples by FT-IR as indicated by high coefficient of variation (R2; 0.96), low bias (0.02 μg m-3, the nominal IMPROVE sample volume is 32.8 m3), low error (0.08 μg m-3) and low normalized error (11%). These performance metrics can be achieved with various degrees of spectral pretreatment (e.g., including or excluding substrate contributions to the absorbances) and are comparable in precision to collocated TOR measurements. FT-IR spectra are also

Identification of Palmitoleic Acid Controlled by mTOR Signaling as a Biomarker of Polymyositis

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Geng Yin

2017-01-01

Full Text Available Polymyositis (PM is a chronic disease characterized by muscle pain, weakness, and increase in muscle-related enzymes, accompanied with inflammations in lymphocytes. However, it is not well understood how the molecular alternations in lymphocytes contribute to the development of polymyositis. The mechanistic target of rapamycin (mTOR signaling is the central regulator of metabolism and inflammation in mammalian cells. Based on previous studies, we proposed that mTOR signaling may control inflammatory reactions via lipid metabolism. In this study, we aim to figure out the role of mTOR signaling in the development of polymyositis and identify novel biomarkers for the detection and therapy of polymyositis. After screening and validation, we found that palmitoleic acid, a monounsaturated fatty acid, is highly regulated by mTOR signaling. Inhibition of mTORC1 activity decreases palmitoleic acid level. Moreover, mTORC1 regulates the level of palmitoleic acid by controlling its de novo synthesis. Importantly, increased palmitoleic acid has been proven to be a marker of polymyositis. Our work identifies palmitoleic acid in peripheral blood mononuclear cells (PBMC as a biomarker of polymyositis and offers new targets to the clinical therapy.

FXR blocks the growth of liver cancer cells through inhibiting mTOR-s6K pathway

Energy Technology Data Exchange (ETDEWEB)

Huang, Xiongfei, E-mail: xiongfeihuang@hotmail.com [Department of Pathology and Institute of Oncology, Preclinical School, Fujian Medical University, Fuzhou 350108, Fujian (China); Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou 350108, Fujian (China); Zeng, Yeting [Department of Pathology and Institute of Oncology, Preclinical School, Fujian Medical University, Fuzhou 350108, Fujian (China); Wang, Xinrui [Department of Biochemistry and Molecular Biology, Fujian Medical University, Fuzhou 350108, Fujian (China); Ma, Xiaoxiao [Department of Diabetes Complications and Metabolism, Diabetes & Metabolism Research Institute, Beckman Research Institute, City of Hope, CA 91010 (United States); Li, Qianqian; Li, Ningbo; Su, Hongying [Department of Pathology and Institute of Oncology, Preclinical School, Fujian Medical University, Fuzhou 350108, Fujian (China); Huang, Wendong [Department of Diabetes Complications and Metabolism, Diabetes & Metabolism Research Institute, Beckman Research Institute, City of Hope, CA 91010 (United States)

2016-05-27

The nuclear receptor Farnesoid X Receptor (FXR) is likely a tumor suppressor in liver tissue but its molecular mechanism of suppression is not well understood. In this study, the gene expression profile of human liver cancer cells was investigated by microarray. Bioinformatics analysis of these data revealed that FXR might regulate the mTOR/S6K signaling pathway. This was confirmed by altering the expression level of FXR in liver cancer cells. Overexpression of FXR prevented the growth of cells and induced cell cycle arrest, which was enhanced by the mTOR/S6K inhibitor rapamycin. FXR upregulation also intensified the inhibition of cell growth by rapamycin. Downregulation of FXR produced the opposite effect. Finally, we found that ectopic expression of FXR in SK-Hep-1 xenografts inhibits tumor growth and reduces expression of the phosphorylated protein S6K. Taken together, our data provide the first evidence that FXR suppresses proliferation of human liver cancer cells via the inhibition of the mTOR/S6K signaling pathway. FXR expression can be used as a biomarker of personalized mTOR inhibitor treatment assessment for liver cancer patients. -- Highlights: •FXR inhibits the proliferation of liver cancer cells by prolonging G0/G1 phase. •Microarray results indicate that mTOR-S6k signaling is involved in cellular processes in which FXR plays an important role. •FXR blocks the growth of liver cancer cells via the inhibition of the mTOR/S6K signaling pathway in vitro and in vivo.

FXR blocks the growth of liver cancer cells through inhibiting mTOR-s6K pathway

International Nuclear Information System (INIS)

Huang, Xiongfei; Zeng, Yeting; Wang, Xinrui; Ma, Xiaoxiao; Li, Qianqian; Li, Ningbo; Su, Hongying; Huang, Wendong

2016-01-01

The nuclear receptor Farnesoid X Receptor (FXR) is likely a tumor suppressor in liver tissue but its molecular mechanism of suppression is not well understood. In this study, the gene expression profile of human liver cancer cells was investigated by microarray. Bioinformatics analysis of these data revealed that FXR might regulate the mTOR/S6K signaling pathway. This was confirmed by altering the expression level of FXR in liver cancer cells. Overexpression of FXR prevented the growth of cells and induced cell cycle arrest, which was enhanced by the mTOR/S6K inhibitor rapamycin. FXR upregulation also intensified the inhibition of cell growth by rapamycin. Downregulation of FXR produced the opposite effect. Finally, we found that ectopic expression of FXR in SK-Hep-1 xenografts inhibits tumor growth and reduces expression of the phosphorylated protein S6K. Taken together, our data provide the first evidence that FXR suppresses proliferation of human liver cancer cells via the inhibition of the mTOR/S6K signaling pathway. FXR expression can be used as a biomarker of personalized mTOR inhibitor treatment assessment for liver cancer patients. -- Highlights: •FXR inhibits the proliferation of liver cancer cells by prolonging G0/G1 phase. •Microarray results indicate that mTOR-S6k signaling is involved in cellular processes in which FXR plays an important role. •FXR blocks the growth of liver cancer cells via the inhibition of the mTOR/S6K signaling pathway in vitro and in vivo.

Malaysian Container Seaport-Hinterland Connectivity: Status, Challenges and Strategies

Directory of Open Access Journals (Sweden)

Shu-Ling Chen

2016-09-01

Full Text Available This paper adopts a qualitative methodology to assess the Malaysian container seaport-hinterland connectivity from the perspective of its physical properties. The findings reveal that although Malaysia's major container seaports are connected to the hinterlands through road and rail transport, they are highly dependent on road. These seaports are also connected to inland freight facilities such as dry ports and ICDs, which are positioned as transit points to help connect exporters and importers in the hinterlands to seaports as well as facilitating regional and cross-border trades. This paper suggests that the quality of hinterland connectivity of Malaysian container seaports could be improved by implementing strategies which tackle the existing challenges including overcoming an extremely imbalanced modal split, insufficient rail capacity and limited train services, increasing road congestion and the limitations of space restriction in some inland facilities.

Level of understanding of innovation among the Malaysian executives

Science.gov (United States)

Abidin, Norkisme Zainal; Suradi, Nur Riza Mohd; Shahabuddin, Faridatulazna; Mustafa, Zainol; Ismail, Wan Rosmanira

2014-06-01

Innovation is among the most frequently used word in the business world today. While many businessman and executives agree that innovation is needed to sustain their long term business success, many struggle to understand the concept of innovation. This study aims to measure the understanding level of innovation among the Malaysian executives using a survey questionnaire. Questions regarding innovation were posted to the respondents and they were requested to answer either it was True or False. Each respondent was given scores for their correct answers. The score of the right answers were then categorized into low, moderate and high understanding level. Results of the survey revealed that the understanding level of innovation among the Malaysian Executives is still at moderate level thus leading to the failure of many initiatives introduced by the organization or the government.

Newsletter published by Malaysian Nuclear Agency, medium conducive injection of public awareness

International Nuclear Information System (INIS)

Norzehan Ngadiron

2008-01-01

This article discusses the role of the pamphlet issued by the Malaysian Nuclear Agency in promoting public awareness about the use of nuclear technology in the country. In line with the vision of the government to introduce and promote the use of nuclear science and technology in national development, the Malaysian Nuclear Agency has published various brochures in an effort to promote community awareness. In fact, published pamphlets also are symbolic of the important role of the Agency in delivering accurate information to people about nuclear technology. It indirectly nurtures the society to look at nuclear technology to a more positive direction. Brochures are not only targeted towards professionals but it is also distributed to schoolchildren, the public and students of higher education institutions, regardless of race. In conclusion, publish and distribute pamphlets to the community represents the general form of undivided Malaysia Nuclear Agency in the mission to create awareness among Malaysian of nuclear technology and the role of the agency itself. Any information will help readers increase awareness and enhance knowledge related to nuclear science and technology.

Neural tube defects in Malaysia: data from the Malaysian National Neonatal Registry.

Science.gov (United States)

Boo, Nem-Yun; Cheah, Irene G S; Thong, Meow-Keong

2013-10-01

This study aimed to determine the prevalence and early outcome of neural tube defects (NTDs) in Malaysia. This prospective study included all neonates with NTDs (spina bifida, anencephaly, encephalocoele) born in 2009 in 32 Malaysian hospitals in the Malaysian National Neonatal Network. The prevalence of NTDs was 0.42 per 1000 live births, being highest among the indigenous people of Sarawak (1.09 per 1000 live births) and lowest among Malaysians of Chinese descent (0.09 per 1000 live births). The most common type of NTDs was anencephaly (0.19 per 1000 live births), followed by spina bifida (0.11 per 1000 live births) and encephalocoele (0.07 per 1000 live births). Majority of the infants with anencephaly (94.5%, n = 51), 45.8% (n = 11) with encephalocoele and 9.5% (n = 4) with spina bifida died. The median duration of hospital stay was 4 (range: 0-161) days. NTDs were common in Malaysia. Mortality was high. Long-term monitoring of NTD prevalence following folic fortification of food is recommended.

Readiness towards Entrepreneurship Education: Students and Malaysian Universities

Science.gov (United States)

Othman, Norasmah; Hashim, Norashidah; Wahid, Hariyaty Ab

2012-01-01

Purpose: The purpose of this paper is to observe the readiness of students and the internal environment of Malaysian public universities in the implementation of entrepreneurship education. Design/methodology/approach: The authors employed a quantitative approach and the main instrument used to gauge the entrepreneurship readiness among students…

Malaysian Private Education Quality: Application of SERVQUAL Model

Science.gov (United States)

Vaz, Anthony; Mansori, Shaheen

2013-01-01

Intense competition among existing private education providers and the Malaysian government's relaxation of regulations for allowing international universities to open off shore campuses in Malaysia, have forced companies in the education industry to develop strategies which can help them to make their existing students satisfied and keep them…

Exploring the clean development mechanism: Malaysian case study

DEFF Research Database (Denmark)

Pedersen, Anne Rathmann

2008-01-01

During 2006 the CDM market in Malaysia became established and by December 2007 a total of 20 Malaysian projects had registered with the CDM Executive Board. The Kyoto Protocol defines the Annex I countries, as countries that are obliged to reduce their greenhouse gas (GHG) emissions and the clean...

MicroRNA-99 family targets AKT/mTOR signaling pathway in dermal wound healing.

Science.gov (United States)

Jin, Yi; Tymen, Stéphanie D; Chen, Dan; Fang, Zong Juan; Zhao, Yan; Dragas, Dragan; Dai, Yang; Marucha, Phillip T; Zhou, Xiaofeng

2013-01-01

Recent studies suggest that microRNAs play important roles in dermal wound healing and microRNA deregulation has been linked with impaired wound repair. Here, using a mouse experimental wound healing model, we identified a panel of 63 differentially expressed microRNAs during dermal wound healing, including members of miR-99 family (miR-99a, miR-99b, miR-100). We further demonstrated that miR-99 family members regulate cell proliferation, cell migration, and AKT/mTOR signaling. Combined experimental and bioinformatics analyses revealed that miR-99 family members regulate AKT/mTOR signaling by targeting multiple genes, including known target genes (e.g., IGF1R, mTOR) and a new target (AKT1). The effects of miR-99 family members on the expression of IGF1R, mTOR and AKT1 were validated at both the mRNA and protein levels. Two adjacent miR-99 family targeting sites were identified in the 3'-UTR of the AKT1 mRNA. The direct interaction of miR-100 with these targeting sites was confirmed using luciferase reporter assays. The microRNA-100-directed recruitment of AKT1 mRNA to the RNAi-induced silencing complex (RISC) was confirmed by a ribonucleoprotein-IP assay. In summary, we identified a panel of differentially expressed microRNAs which may play important roles in wound healing. We provide evidence that miR-99 family members contribute to wound healing by regulating the AKT/mTOR signaling.

Intellectual Capital: A Focus on Human Capital Reporting Practices of Top Malaysian Listed Companies

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Norhayati Mat Husin

2011-04-01

Full Text Available This paper aims to examine the extent of human capital (HC reporting among top Malaysian companies and introduce an HC reporting guideline that can be used by Malaysian companies and regulator. It begins by developing the HC framework based on previous intellectual capital (IC frameworks. This framework is then used to examine each of the top 100 Malaysian companies listed on the Bursa Malaysia in year 2008. Using the content analysis method, it reviews the annual reports of these companies to determine the extent of HC reporting. The findings of this paper highlight the need for the development of IC framework particularly on HC. HC differences were also identified between Malaysia and other countries such as Sri Lanka and Australia, and it is argued that these differences can be attributed to the social, economic, and political factors.

Editorial: HOW THE CENTRE OF MALAYSIAN POLITICS SHIFTED TO THE ISLAMIST REGISTER 1969-2009

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Editor Al-Jami'ah: Journal of Islamic Studies

2009-02-01

Full Text Available One of the most obvious observations that can be made about the form and content of Malaysian politics, political discourse and political culture today is how the country has shifted to a visibly more Islamist register, with the symbols and vocabulary of political Islam gaining prominence and visibility over the past four decades. This is particularly true in the case of Malaysia’s civil society space, which was once dominated by secular Non-Governmental Organisations (NGOs, mass movements and lobby groups. Today, however, we are looking at the relatively new phenomenon of a Malaysian civil society space which is increasingly being dominated by Islamist civil society movements that operate within the constitutional framework of the country but which are pushing for a clearly religious-communitarian agenda, namely the Islamisation of Malaysian society and politics. How did this come about?

Forkhead, a new cross regulator of metabolism and innate immunity downstream of TOR in Drosophila.

Science.gov (United States)

Varma, Disha; Bülow, Margret H; Pesch, Yanina-Yasmin; Loch, Gerrit; Hoch, Michael

2014-10-01

Antimicrobial peptides (AMPs) are conserved cationic peptides which act both as defense molecules of the host immune system and as regulators of the commensal microbiome. Expression of AMPs is induced in response to infection by the Toll and Imd pathway. Under non-infected conditions, the transcription factor dFOXO directly regulates a set of AMP expression at low levels when nutrients are limited. Here we have analyzed whether target of rapamycin (TOR), another major regulator of growth and metabolism, also modulates AMP responses in Drosophila. We found that downregulation of TOR by feeding the drug rapamycin or by overexpressing the negative TOR regulators TSC1/TSC2, resulted in a specific induction of the AMPs Diptericin (Dpt) and Metchnikowin (Mtk). In contrast, overexpression of Rheb, which positively regulates TOR led to a repression of the two AMPs. Genetic and pharmacological experiments indicate that Dpt and Mtk activation is controlled by the transcription factor Forkhead (FKH), the founding member of the FoxO family. Shuttling of FKH from the cytoplasm to the nucleus is induced in the fat body and in the posterior midgut in response to TOR downregulation. The FKH-dependent induction of Dpt and Mtk can be triggered in dFOXO null mutants and in immune-compromised Toll and IMD pathway mutants indicating that FKH acts in parallel to these regulators. Together, we have discovered that FKH is the second conserved member of the FoxO family cross-regulating metabolism and innate immunity. dFOXO and FKH, which are activated upon downregulation of insulin or TOR activities, respectively, act in parallel to induce different sets of AMPs, thereby modulating the immune status of metabolic tissues such as the fat body or the gut in response to the oscillating energy status of the organism. Copyright © 2014 Elsevier Ltd. All rights reserved.

Joint inhibition of TOR and JNK pathways interacts to extend the lifespan of Brachionus manjavacas (Rotifera).

Science.gov (United States)

Snell, Terry W; Johnston, Rachel K; Rabeneck, Brett; Zipperer, Cody; Teat, Stephanie

2014-04-01

The TOR kinase pathway is central in modulating aging in a variety of animal models. The target of rapamycin (TOR) integrates a complex network of signals from growth conditions, nutrient availability, energy status, and physiological stresses and matches an organism's growth rate to the resource environment. Important remaining problems are the identification of the pathways that interact with TOR and their characterization as additive or synergistic. One of the most versatile stress sensors in metazoans is the Jun-N-terminal kinase (JNK) signaling pathway. JNK is an evolutionarily conserved stress-activated protein kinase that is induced by a range of stressors, including UV irradiation, reactive oxygen species, DNA damage, heat, and bacterial antigens. JNK is thought to interact with the TOR pathway, but its effects on TOR are poorly understood. We used the rotifer Brachionus manjavacas as a model animal to probe the regulation of TOR and JNK pathways and explore their interaction. The effect of various chemical inhibitors was examined in life table and stressor challenge experiments. A survey of 12 inhibitors revealed two, rapamycin and JNK inhibitor, that significantly extended lifespan of B. manjavacas. At 1 μM concentration, exposure to rapamycin or JNK inhibitor extended mean rotifer lifespan by 35% and maximum lifespan by 37%. Exposure to both rapamycin and JNK inhibitor simultaneously extended mean rotifer lifespan by 65% more than either alone. Exposure to a combination of rapamycin and JNK inhibitors conveyed greater protection to starvation, UV and osmotic stress than either inhibitor alone. RNAi knockdown of TOR and JNK gene expression was investigated for its ability to extend rotifer lifespan. RNAi knockdown of the TOR gene resulted in 29% extension of the mean lifespan compared to control and knockdown of the JNK gene resulted in 51% mean lifespan extension. In addition to the lifespan, we quantified mitochondria activity using the fluorescent

Aminoacyl-tRNA quality control is required for efficient activation of the TOR pathway regulator Gln3p.

Science.gov (United States)

Mohler, Kyle; Mann, Rebecca; Kyle, Amanda; Reynolds, Noah; Ibba, Michael

2017-09-14

The aminoacylation status of the cellular tRNA pool regulates both general amino acid control (GAAC) and target of rapamycin (TOR) stress response pathways in yeast. Consequently, fidelity of translation at the level of aminoacyl-tRNA synthesis plays a central role in determining accuracy and sensitivity of stress responses. To investigate effects of translational quality control (QC) on cell physiology under stress conditions, phenotypic microarray analyses were used to identify changes in QC deficient cells. Nitrogen source growth assays showed QC deficient yeast grew differently compared to WT. The QC deficient strain was more tolerant to caffeine treatment than wild type through altered interactions with the TOR and GAAC pathways. Increased caffeine tolerance of the QC deficient strain was consistent with the observation that the activity of Gln3p, a transcription factor controlled by the TOR pathway, is decreased in the QC deficient strain compared to WT. GCN4 translation, which is typically repressed in the absence of nutritional stress, was enhanced in the QC deficient strain through TOR inhibition. QC did not impact cell cycle regulation; however, the chronological lifespan of QC deficient yeast strains decreased compared to wild type, likely due to translational errors and alteration of the TOR-associated regulon. These findings support the idea that changes in translational fidelity provide a mechanism of cellular adaptation by modulating TOR activity. This, in turn, supports a central role for aminoacyl-tRNA synthesis QC in the integrated stress response by maintaining the proper aa-tRNA pools necessary to coordinate the GAAC and TOR.

Insights into significance of combined inhibition of MEK and m-TOR signalling output in KRAS mutant non-small-cell lung cancer.

Science.gov (United States)

Broutin, Sophie; Stewart, Adam; Thavasu, Parames; Paci, Angelo; Bidart, Jean-Michel; Banerji, Udai

2016-08-23

We aimed to understand the dependence of MEK and m-TOR inhibition in EGFR(WT)/ALK(non-rearranged) NSCLC cell lines. In a panel of KRAS(M) and KRAS(WT) NSCLC cell lines, we determined growth inhibition (GI) following maximal reduction in p-ERK and p-S6RP caused by trametinib (MEK inhibitor) and AZD2014 (m-TOR inhibitor), respectively. GI caused by maximal m-TOR inhibition was significantly greater than GI caused by maximal MEK inhibition in the cell line panel (52% vs 18%, PTOR compared with maximal m-TOR+MEK inhibition. However, GI caused by the combination was significantly greater in the KRAS(M) cell lines (79% vs 61%, P=0.017). m-TOR inhibition was more critical to GI than MEK inhibition in EGFR(WT)/ALK(non-rearranged) NSCLC cells. The combination of MEK and m-TOR inhibition was most effective in KRAS(M) cells.

Inhibition of Akt/mTOR Signaling by the Dietary Flavonoid Fisetin

Science.gov (United States)

Syed, Deeba N.; Adhami, Vaqar M.; Khan, Mohammad Imran; Mukhtar, Hasan

2014-01-01

Plants have long been providing mankind with remedies of different ailments. Flavonoids, a family of naturally occurring polyphenolic compounds are ubiquitous in plants. Development of polyphenol-based drugs has not attracted much attention by researchers and drug companies. Therefore, despite extensive studies on polyphenols, this vast group of compounds is underrepresented in clinical medicine. Fisetin (3,7,3’,4’-tetrahydroxyflavone) belongs to the flavonol subgroup of flavonoids together with quercetin, myricetin and kaempferol and is found in several fruits and vegetables including strawberries, apples, persimmons and onions. Fisetin is showing promise as a useful natural agent against cancer and has been evaluated for its potential inhibitory role against cancer in several in vitro and in vivo studies. The Akt/mTOR pathway is known to play a central role in various cellular processes that contribute to the malignant phenotype. Accordingly, inhibition of this signaling cascade has been a focus of recent therapeutic studies. Novel inhibitors of PI3-K, Akt, and mTOR are now passing through early phase clinical trials. Herein, we review the effect of fisetin on the PI3-K/Akt/mTOR pathway as studied in different cancer cell models. PMID:23293889

Towards Malaysian LADM Country Profile for 2D and 3D Cadastral Registration System

OpenAIRE

Zulkifli, N.A.; Abdul Rahman, A.; Jamil, H.; Teng, C.H.; Tan, L.C.; Looi, K.S.; Chan, K.L.; Van Oosterom, P.J.M.

2014-01-01

This paper proposes a comprehensive Land Administration Domain Model (LADM, ISO 2012) country profile for 2D and 3D cadastral registration system for Malaysia. The proposed Malaysian country profile is partly based on the existing spatial (including survey) and administrative registration systems, and partly based on new developments inspired by the LADM standard. Within the country profile, an attempt is made to cover all Malaysian land administration related information, which are maintaine...

SnRK1 activates autophagy via the TOR signaling pathway in Arabidopsis thaliana.

Science.gov (United States)

Soto-Burgos, Junmarie; Bassham, Diane C

2017-01-01

Autophagy is a degradation process in which cells break down and recycle their cytoplasmic contents when subjected to environmental stress or during cellular remodeling. The Arabidopsis thaliana SnRK1 complex is a protein kinase that senses changes in energy levels and triggers downstream responses to enable survival. Its mammalian ortholog, AMPK, and yeast ortholog, Snf-1, activate autophagy in response to low energy conditions. We therefore hypothesized that SnRK1 may play a role in the regulation of autophagy in response to nutrient or energy deficiency in Arabidopsis. To test this hypothesis, we determined the effect of overexpression or knockout of the SnRK1 catalytic subunit KIN10 on autophagy activation by abiotic stresses, including nutrient deficiency, salt, osmotic, oxidative, and ER stress. While wild-type plants had low basal autophagy activity in control conditions, KIN10 overexpression lines had increased autophagy under these conditions, indicating activation of autophagy by SnRK1. A kin10 mutant had a basal level of autophagy under control conditions similar to wild-type plants, but activation of autophagy by most abiotic stresses was blocked, indicating that SnRK1 is required for autophagy induction by a wide variety of stress conditions. In mammals, TOR is a negative regulator of autophagy, and AMPK acts to activate autophagy both upstream of TOR, by inhibiting its activity, and in a parallel pathway. Inhibition of Arabidopsis TOR leads to activation of autophagy; inhibition of SnRK1 did not block this activation. Furthermore, an increase in SnRK1 activity was unable to induce autophagy when TOR was also activated. These results demonstrate that SnRK1 acts upstream of TOR in the activation of autophagy in Arabidopsis.

Ecografia na patologia torácica

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António Bugalho

2010-07-01

Full Text Available Resumo: Nos últimos anos a ecografia torácica tem vindo a ser reconhecida como um instrumento de extrema importância para os pneumologistas. Actualmente, os equipamentos são práticos, portáteis, de fácil utilização e fidedignos, o que os torna apropriados para utilização no diagnóstico e orientação de procedimentos terapêuticos.Na avaliação de derrame pleural e condução de toracentese são necessárias competências técnicas básicas em ultra-sonografia. Procedimentos mais complexos devem ser realizados perante treino específico e incluem a colocação de dreno torácico e identificação com eventual biopsia de lesões torácicas.Os autores procuram abordar, de um ponto de vista prático, a técnica e os recentes avanços alcançados neste campo. São apresentados alguns casos clínicos no sentido de ilustrar e guiar aqueles que desejam iniciar a realização de ecografia do tórax.Rev Port Pneumol 2010; XVI (4: 589-606 Abstract: In the past few years transthoracic ultrasound has been recognized as an important tool for chest physicians. At present, ultrasound devices are practical, portable, easy to use and reliable, which makes them suited for diagnostic investigations as well as for therapeutic procedures guidance.Basic ultrasound technical expertise is required to assess pleural effusions and perform ultrasound-guided thoracentesis. More complex procedures can be done with specific training and include assistance to chest drain insertion and identification with potential biopsy of thoracic lesions.The authors aim to review, in a practical approach, the technique and recent developments in this field. Clinical cases are presented in order to illustrate and guide the beginner in chest ultrasound.Rev Port Pneumol 2010; XVI (4: 589-606 Palavras-chave: Ecografia, ultra-sonografia, tórax, pleura, doenças pulmonares, derrame pleural, cancro do pulmão, Key-words: Ultrasound, sonography, chest, thorax, pleura, lung diseases

Ecografia na patologia torácica

Directory of Open Access Journals (Sweden)

António Bugalho

2010-07-01

Full Text Available Resumo: Nos últimos anos a ecografia torácica tem vindo a ser reconhecida como um instrumento de extrema importância para os pneumologistas. Actualmente, os equipamentos são práticos, portáteis, de fácil utilização e fidedignos, o que os torna apropriados para utilização no diagnóstico e orientação de procedimentos terapêuticos.Na avaliação de derrame pleural e condução de toracentese são necessárias competências técnicas básicas em ultra-sonografia. Procedimentos mais complexos devem ser realizados perante treino específico e incluem a colocação de dreno torácico e identificação com eventual biopsia de lesões torácicas.Os autores procuram abordar, de um ponto de vista prático, a técnica e os recentes avanços alcançados neste campo. São apresentados alguns casos clínicos no sentido de ilustrar e guiar aqueles que desejam iniciar a realização de ecografia do tórax. Abstract: In the past few years transthoracic ultrasound has been recognized as an important tool for chest physicians. At present, ultrasound devices are practical, portable, easy to use and reliable, which makes them suited for diagnostic investigations as well as for therapeutic procedures guidance.Basic ultrasound technical expertise is required to assess pleural effusions and perform ultrasound-guided thoracentesis. More complex procedures can be done with specific training and include assistance to chest drain insertion and identification with potential biopsy of thoracic lesions.The authors aim to review, in a practical approach, the technique and recent developments in this field. Clinical cases are presented in order to illustrate and guide the beginner in chest ultrasound. Palavras-chave: Ecografia, ultra-sonografia, tórax, pleura, doenças pulmonares, derrame pleural, cancro do pulmão, Key-words: Ultrasound, sonography, chest, thorax, pleura, lung diseases, pleural effusion, lung cancer

Are Modal Auxiliaries in Malaysian English Language Textbooks in Line with Their Usage in Real Language?

Science.gov (United States)

Khojasteh, Laleh; Kafipour, Reza

2012-01-01

Based on the discrepancies found in many Malaysian English language textbooks, a detailed analysis on the way modal auxiliary verb forms and their semantic functions were introduced and presented in texts and exercises in five Malaysian textbooks was done. For that to be achieved, a qualitative page-by-page content analysis was applied. From the…

MenTORing Immunity: mTOR Signaling in the Development and Function of Tissue-Resident Immune Cells.

Science.gov (United States)

Jones, Russell G; Pearce, Edward J

2017-05-16

Tissue-resident immune cells must balance survival in peripheral tissues with the capacity to respond rapidly upon infection or tissue damage, and in turn couple these responses with intrinsic metabolic control and conditions in the tissue microenvironment. The serine/threonine kinase mammalian/mechanistic target of rapamycin (mTOR) is a central integrator of extracellular and intracellular growth signals and cellular metabolism and plays important roles in both innate and adaptive immune responses. This review discusses the function of mTOR signaling in the differentiation and function of tissue-resident immune cells, with focus on the role of mTOR as a metabolic sensor and its impact on metabolic regulation in innate and adaptive immune cells. We also discuss the impact of metabolic constraints in tissues on immune homeostasis and disease, and how manipulating mTOR activity with drugs such as rapamycin can modulate immunity in these contexts. Copyright © 2017. Published by Elsevier Inc.

Torness computer system turns round data

International Nuclear Information System (INIS)

Dowler, E.; Hamilton, J.

1989-01-01

The Torness nuclear power station has two advanced gas-cooled reactors. A key feature is the distributed computer system which covers both data processing and auto-control. The complete computer system has over 80 processors with 45000 digital and 22000 analogue input signals. The on-line control and monitoring systems includes operating systems, plant data acquisition and processing, alarm and event detection, communications software, process management systems and database management software. Some features of the system are described. (UK)

Torness delay is storing up trouble

International Nuclear Information System (INIS)

Cavenagh, Andrew.

1994-01-01

A recent decision by the Scottish Office to delay planning permission for the construction of a 50 million dry store for spent nuclear fuel at Torness Power Station is proving frustrating and inexplicable to many in the nuclear industry. The possible reasons for this apparent about face in government policy on spent fuel management are debated and the economic ramifications of the decision for British Nuclear Fuels Limited (BNFL), if the store were to go ahead, are outlined. (UK)

Effects Of Rotation On Auditor Independence And Quality Of Audit Service In Malaysian Banking Industry

Directory of Open Access Journals (Sweden)

Kabiru Isa Dandago

2012-12-01

means for ensuring auditor independence and high audit quality in the Malaysian banking industry. In the absence of statutory/mandatory requirement for auditor rotation, it is recommended that the Malaysian banking institutions should be carefully evaluating the impact auditor rotation would have on the quality of audit work on their current and future financial statements, as they decide whether to rotate their auditors or not.

Complicaciones usuales post-drenaje pleural con tubos endotorácico en el trauma torácico no

OpenAIRE

Juan C Araujo-Cuauro; Fernando Fernández-Parra; Edwinis Garcia-Fontalvo; Milagros Sánchez

2016-01-01

Las lesiones por trauma torácico que ameriten hospitalización, y la inserción de un tubo endotorácico El objetivo de la investigación es identificar las complicaciones post-drenaje pleural con tubos endotorácico en el trauma torácico no quirúrgico. Se trata de estudio prospectivo descriptivo y observacional de las historias clínicas de admisión de los pacientes con traumatismo torácico contuso o penetrante no quirúrgico, que ingresaron durante el período co...

Transcultural diabetes nutrition algorithm: a malaysian application.

Science.gov (United States)

Hussein, Zanariah; Hamdy, Osama; Chin Chia, Yook; Lin Lim, Shueh; Kumari Natkunam, Santha; Hussain, Husni; Yeong Tan, Ming; Sulaiman, Ridzoni; Nisak, Barakatun; Chee, Winnie Siew Swee; Marchetti, Albert; Hegazi, Refaat A; Mechanick, Jeffrey I

2013-01-01

Glycemic control among patients with prediabetes and type 2 diabetes mellitus (T2D) in Malaysia is suboptimal, especially after the continuous worsening over the past decade. Improved glycemic control may be achieved through a comprehensive management strategy that includes medical nutrition therapy (MNT). Evidence-based recommendations for diabetes-specific therapeutic diets are available internationally. However, Asian patients with T2D, including Malaysians, have unique disease characteristics and risk factors, as well as cultural and lifestyle dissimilarities, which may render international guidelines and recommendations less applicable and/or difficult to implement. With these thoughts in mind, a transcultural Diabetes Nutrition Algorithm (tDNA) was developed by an international task force of diabetes and nutrition experts through the restructuring of international guidelines for the nutritional management of prediabetes and T2D to account for cultural differences in lifestyle, diet, and genetic factors. The initial evidence-based global tDNA template was designed for simplicity, flexibility, and cultural modification. This paper reports the Malaysian adaptation of the tDNA, which takes into account the epidemiologic, physiologic, cultural, and lifestyle factors unique to Malaysia, as well as the local guidelines recommendations.

Anti-gout Potential of Malaysian Medicinal Plants.

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Abu Bakar, Fazleen I; Abu Bakar, Mohd F; Rahmat, Asmah; Abdullah, Norazlin; Sabran, Siti F; Endrini, Susi

2018-01-01

Gout is a type of arthritis that causes painful inflammation in one or more joints. In gout, elevation of uric acid in the blood triggers the formation of crystals, causing joint pain. Malaysia is a mega-biodiversity country that is rich in medicinal plants species. Therefore, its flora might offer promising therapies for gout. This article aims to systematically review the anti-gout potential of Malaysian medicinal plants. Articles on gout published from 2000 to 2017 were identified using PubMed, Scopus, ScienceDirect, and Google Scholar with the following keyword search terms: "gout," "medicinal plants," "Malaysia," "epidemiology," " in vitro," and " in vivo ." In this study, 85 plants were identified as possessing anti-gout activity. These plants had higher percentages of xanthine oxidase inhibitory activity (>85%); specifically, the Momordica charantia, Chrysanthemum indicum, Cinnamomum cassia, Kaempferia galanga, Artemisia vulgaris , and Morinda elliptica had the highest values, due to their diverse natural bioactive compounds, which include flavonoids, phenolics, tannin, coumarins, luteolin, and apigenin. This review summarizes the anti-gout potential of Malaysian medicinal plants but the mechanisms, active compounds, pharmacokinetics, bioavailability, and safety of the plants still remain to be elucidated.

Transcultural Diabetes Nutrition Algorithm: A Malaysian Application

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Zanariah Hussein

2013-01-01

Full Text Available Glycemic control among patients with prediabetes and type 2 diabetes mellitus (T2D in Malaysia is suboptimal, especially after the continuous worsening over the past decade. Improved glycemic control may be achieved through a comprehensive management strategy that includes medical nutrition therapy (MNT. Evidence-based recommendations for diabetes-specific therapeutic diets are available internationally. However, Asian patients with T2D, including Malaysians, have unique disease characteristics and risk factors, as well as cultural and lifestyle dissimilarities, which may render international guidelines and recommendations less applicable and/or difficult to implement. With these thoughts in mind, a transcultural Diabetes Nutrition Algorithm (tDNA was developed by an international task force of diabetes and nutrition experts through the restructuring of international guidelines for the nutritional management of prediabetes and T2D to account for cultural differences in lifestyle, diet, and genetic factors. The initial evidence-based global tDNA template was designed for simplicity, flexibility, and cultural modification. This paper reports the Malaysian adaptation of the tDNA, which takes into account the epidemiologic, physiologic, cultural, and lifestyle factors unique to Malaysia, as well as the local guidelines recommendations.

Transcultural Diabetes Nutrition Algorithm: A Malaysian Application

Science.gov (United States)

Hamdy, Osama; Chin Chia, Yook; Lin Lim, Shueh; Kumari Natkunam, Santha; Yeong Tan, Ming; Sulaiman, Ridzoni; Nisak, Barakatun; Chee, Winnie Siew Swee; Marchetti, Albert; Hegazi, Refaat A.; Mechanick, Jeffrey I.

2013-01-01

Glycemic control among patients with prediabetes and type 2 diabetes mellitus (T2D) in Malaysia is suboptimal, especially after the continuous worsening over the past decade. Improved glycemic control may be achieved through a comprehensive management strategy that includes medical nutrition therapy (MNT). Evidence-based recommendations for diabetes-specific therapeutic diets are available internationally. However, Asian patients with T2D, including Malaysians, have unique disease characteristics and risk factors, as well as cultural and lifestyle dissimilarities, which may render international guidelines and recommendations less applicable and/or difficult to implement. With these thoughts in mind, a transcultural Diabetes Nutrition Algorithm (tDNA) was developed by an international task force of diabetes and nutrition experts through the restructuring of international guidelines for the nutritional management of prediabetes and T2D to account for cultural differences in lifestyle, diet, and genetic factors. The initial evidence-based global tDNA template was designed for simplicity, flexibility, and cultural modification. This paper reports the Malaysian adaptation of the tDNA, which takes into account the epidemiologic, physiologic, cultural, and lifestyle factors unique to Malaysia, as well as the local guidelines recommendations. PMID:24385984

THE IMPACT OF PERSONALITY AND LEADERSHIP STYLES ON LEADING CHANGE CAPABILITY OF MALAYSIAN MANAGERS

OpenAIRE

Ali Hussein Alkahtani; Ismael Abu-Jarad; Mohamed Sulaiman; Davoud Nikbin

2011-01-01

This study was conducted to investigate the influence of the Big Five Dimensions of personality of the Malaysian Managers and the leadership styles these managers use on their leading change capabilities. Total sample of 105 managers was used in this study. The results of this study revealed that the Malaysian managers tend to enjoy personalities that are conscious and open to experience. These managers tend to use consultative leadership style. However, they use autocratic, democratic and so...

The effector AWR5 from the plant pathogen Ralstonia solanacearum is an inhibitor of the TOR signalling pathway.

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Popa, Crina; Li, Liang; Gil, Sergio; Tatjer, Laura; Hashii, Keisuke; Tabuchi, Mitsuaki; Coll, Núria S; Ariño, Joaquín; Valls, Marc

2016-06-03

Bacterial pathogens possess complex type III effector (T3E) repertoires that are translocated inside the host cells to cause disease. However, only a minor proportion of these effectors have been assigned a function. Here, we show that the T3E AWR5 from the phytopathogen Ralstonia solanacearum is an inhibitor of TOR, a central regulator in eukaryotes that controls the switch between cell growth and stress responses in response to nutrient availability. Heterologous expression of AWR5 in yeast caused growth inhibition and autophagy induction coupled to massive transcriptomic changes, unmistakably reminiscent of TOR inhibition by rapamycin or nitrogen starvation. Detailed genetic analysis of these phenotypes in yeast, including suppression of AWR5-induced toxicity by mutation of CDC55 and TPD3, encoding regulatory subunits of the PP2A phosphatase, indicated that AWR5 might exert its function by directly or indirectly inhibiting the TOR pathway upstream PP2A. We present evidence in planta that this T3E caused a decrease in TOR-regulated plant nitrate reductase activity and also that normal levels of TOR and the Cdc55 homologues in plants are required for R. solanacearum virulence. Our results suggest that the TOR pathway is a bona fide T3E target and further prove that yeast is a useful platform for T3E function characterisation.

Identification of the Raptor-binding motif on Arabidopsis S6 kinase and its use as a TOR signaling suppressor.

Science.gov (United States)

Son, Ora; Kim, Sunghan; Hur, Yoon-Sun; Cheon, Choong-Ill

2016-03-25

TOR (target of rapamycin) kinase signaling plays central role as a regulator of growth and proliferation in all eukaryotic cells and its key signaling components and effectors are also conserved in plants. Unlike the mammalian and yeast counterparts, however, we found through yeast two-hybrid analysis that multiple regions of the Arabidopsis Raptor (regulatory associated protein of TOR) are required for binding to its substrate. We also identified that a 44-amino acid region at the N-terminal end of Arabidopsis ribosomal S6 kinase 1 (AtS6K1) specifically interacted with AtRaptor1, indicating that this region may contain a functional equivalent of the TOS (TOR-Signaling) motif present in the mammalian TOR substrates. Transient over-expression of this 44-amino acid fragment in Arabidopsis protoplasts resulted in significant decrease in rDNA transcription, demonstrating a feasibility of developing a new plant-specific TOR signaling inhibitor based upon perturbation of the Raptor-substrate interaction. Copyright © 2016 Elsevier Inc. All rights reserved.

Modeling Environmental Literacy of Malaysian Pre-University Students

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Shamuganathan, Sheila; Karpudewan, Mageswary

2015-01-01

In this study attempt was made to model the environmental literacy of Malaysian pre-university students enrolled in a matriculation college. Students enrolled in the matriculation colleges in Malaysia are the top notch students in the country. Environmental literacy of this group is perceived important because in the future these students will be…

Sociolinguistic Competence and Malaysian Students' English Language Proficiency

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Muniandy, Mohan K.; Nair, Gopala Krishnan Sekharan; Shanmugam, Shashi Kumar Krishnan; Ahmad, Irma; Noor, Norashikin Binte Mohamed

2010-01-01

This paper aims to highlight the importance of teaching sociolinguistic competence to ESL learners in Malaysian schools. Sociolinguistic competence is the knowledge of socio cultural rules of language and of discourse. This type of competence requires an understanding of the socio context in which language is used. It is proposed that carefully…

Intellectual Capital: A Focus on Human Capital Reporting Practices of Top Malaysian Listed Companies

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Norhayati Mat Husin

2013-07-01

Full Text Available This paper aims to examine the extent of human capital (HC reporting among top Malaysian companies and introduce an HC reporting guideline that can be used by Malaysian companies and regulator. It begins by developing the HC framework based on previous intellectual capital (IC frameworks. This framework is then used to examine each of the top 100 Malaysian companies listed on the Bursa Malaysia in year 2008. Using the content analysis method, it reviews the annual reports of these companies to determine the extent of HC reporting. The findings of this paper highlight the need for the development of IC framework particularly on HC. HC differences were also identified between Malaysia and other countries such as Sri Lanka and Australia, and it is argued that these differences can be attributed to the social, economic, and political factors.Keywords: Human capital, intellectual capital, Malaysia

Malaysian weedy rice shows its true stripes: wild Oryza and elite rice cultivars shape agricultural weed evolution in Southeast Asia.

Science.gov (United States)

Song, Beng-Kah; Chuah, Tse-Seng; Tam, Sheh May; Olsen, Kenneth M

2014-10-01

Weedy rice is a close relative of domesticated rice (Oryza sativa) that competes aggressively with the crop and limits rice productivity worldwide. Most genetic studies of weedy rice have focused on populations in regions where no reproductively compatible wild Oryza species occur (North America, Europe and northern Asia). Here, we examined the population genetics of weedy rice in Malaysia, where wild rice (O. rufipogon) can be found growing in close proximity to cultivated and weedy rice. Using 375 accessions and a combined analysis of 24 neutral SSR loci and two rice domestication genes (sh4, controlling seed shattering, and Bh4, controlling hull colour), we addressed the following questions: (i) What is the relationship of Malaysian weedy rice to domesticated and wild rice, and to weedy rice strains in the USA? (ii) To what extent does the presence of O. rufipogon influence the genetic and phenotypic diversity of Malaysian weeds? (iii) What do the distributions of sh4 and Bh4 alleles and associated phenotypes reveal about the origin and contemporary evolution of Malaysian weedy rice? Our results reveal the following: independent evolutionary origins for Malaysian weeds and US strains, despite their very close phenotypic resemblance; wild-to-weed gene flow in Malaysian weed populations, including apparent adaptive introgression of seed-shattering alleles; and a prominent role for modern Malaysian cultivars in the origin and recent proliferation of Malaysian weeds. These findings suggest that the genetic complexity and adaptability of weedy crop relatives can be profoundly influenced by proximity to reproductively compatible wild and domesticated populations. © 2014 John Wiley & Sons Ltd.

A Descriptive-Comparative Analysis of Apology Strategies: The Case of Iranian EFL and Malaysian ESL University Students

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Farashaiyan, Atieh; Amirkhiz, Seyed Yasin Yazdi

2011-01-01

This paper reports on a study that was carried out to describe and compare the apology strategies utilized by Iranian EFL and Malaysian ESL learners in confronting identical apology situations. For this purpose, data were elicited from 15 Iranian and 15 Malaysian students through a "Discourse completion tasks" questionnaire. The…

Understanding the Perception of Islamic Medicine Among the Malaysian Muslim Community.

Science.gov (United States)

Ahmad, Khadher; Ariffin, Mohd Farhan Md; Deraman, Fauzi; Ariffin, Sedek; Abdullah, Mustaffa; Razzak, Monika Munirah Abd; Yusoff, M Y Zulkifli Mohd; Achour, Meguellati

2017-10-26

This study was conducted to identify and describe the patients' perceptions of Islamic medicine based on gender, age, marital, educational level and working status among the Malaysian Muslim population. A nationwide interviewer-administered questionnaire survey was conducted in 2013. An open-ended questionnaire pertaining to Islamic medicine was used to increase the probability of capturing maximum data. This survey implemented a multistage design, stratified by state, proportionate to the size of the state population and was representative of the Malaysian population. Post-survey classification of results was performed accordingly. Complex data analysis was carried out using SPSS 16.0. The discussion was identified and categorised into various sections. The paper concludes that Islamic medicine has a major influence in the Malaysian Muslim community compared to other alternatives. Further, its potential for growth and importance especially for treating spiritual ailments cannot be denied. The respondents indicated that two factors motivate Islamic medicine in Malaysia: (1) the Muslim community opts for alternative healing because of their dissatisfaction with conventional methods; (2) Islamic medicine focuses only on healing spiritual-related problems. The average perception of respondents is that the function of Islamic medicine in healing physical diseases is undervalued and that it is not suitable to replace the functions of modern health institutions.

The TOR Signaling Pathway in Spatial and Temporal Control of Cell Size and Growth

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Suam Gonzalez

2017-06-01

Full Text Available Cell size is amenable by genetic and environmental factors. The highly conserved nutrient-responsive Target of Rapamycin (TOR signaling pathway regulates cellular metabolic status and growth in response to numerous inputs. Timing and duration of TOR pathway activity is pivotal for both cell mass built up as well as cell cycle progression and is controlled and fine-tuned by the abundance and quality of nutrients, hormonal signals, growth factors, stress, and oxygen. TOR kinases function within two functionally and structurally discrete multiprotein complexes, TORC1 and TORC2, that are implicated in temporal and spatial control of cell size and growth respectively; however, recent data indicate that such functional distinctions are much more complex. Here, we briefly review roles of the two complexes in cellular growth and cytoarchitecture in various experimental model systems.

Covenant Cog or Functional Fourth Estate. A Survey of Malaysian Journalists’ Attitudes towards their Profession

OpenAIRE

Rohini SREEKUMAR; Sony JALARAJAN RAJ

2012-01-01

In Malaysia, the idealistic notion of the news media as ‘watchdog’ is largely redundant due to the external and institutional realities associated with its functioning in a heavily regulated, monitored and controlled media system. There has been little analysis of Malaysian journalists’ perceptions of their profession. Operating within an authoritarian mediascape, Malaysian journalists have to surrender their journalistic values and principles of practice thereby pervading a culture of self-c...

mTORC2 promotes type I insulin-like growth factor receptor and insulin receptor activation through the tyrosine kinase activity of mTOR.