5,782 research outputs found
C-Jun N-terminal kinases/c-Jun and p38 pathways cooperate in ceramide-induced neuronal apoptosis
No full textUnderstanding the regulation of the apoptotic program in neurons by intracellular pathways is currently a subject of great interest. Recent results suggest that c-Jun N-terminal kinases (JNK), mitogen-activated protein kinases and the transcription factor c-Jun are important regulators of this cell death program in post-mitotic neurons following survival-factor withdrawal. Our study demonstrates that ceramide levels increase upon survival-factor withdrawal in primary cultured cortical neurons. Furthermore, survival-factor withdrawal or addition of exogenous c2-ceramide induces JNK pathway activation in these cells. Western blot analyses of JNK and c-Jun using phospho-specific antibodies reveal that JNK and subsequent c-Jun phosphorylation occur hours before the initiation of apoptosis, reflected morphologically by neurite retraction and fragmentation, cell-body shrinkage and chromatin fragmentation. Immunocytochemistry using the same antibodies shows that phospho-JNK are localized in the neurites of control neurons and translocate to the nucleus where phospho-c-Jun concurrently appears upon ceramide-induced apoptosis. To determine if ceramide-induced c-Jun activation is responsible for the induction of the apoptotic program, we performed transient transfections of a dominant negative form of c-Jun, truncated in its transactivation region. Our results show that DNc-Jun partially protects cortical neurons from ceramide-induced apoptosis. Treatment of dominant negative c-Jun-expressing neurons with the pharmacological inhibitor of p38 kinase, SB203580, completely blocked neuronal death. Thus our data show that p38 and JNK/c-Jun pathways cooperate to induce neuronal apoptosis
Separation of Ethyl-(R)-4-chloro-3-hydroxybutyrate from racemic mixture by using bulk liquid membrane
No full textAn Analysis and Implementation of High Fairness Arbitration Mechanism by Using Level-table and Static Priority Orders in Shared Bus Architecture
No full textProto-oncogene c-jun expression is induced by AML1-ETO in a JNK dependent manner:possible role in the pathogenesis of acute myeloid leukemia
No full textOverexpression of proto-oncogene c-jun and constitutive activation of the Jun NH2-terminal kinase (JNK) signaling pathway have been implicated in the leukemic transformation process. However, c-jun expression has not been investigated in acute myeloid leukemia (AML) cells containing the most common chromosomal translocations. t(8;21) is one of the most common AML-associated translocation and results in the AML1-ETO fusion protein. Overexpression of AML1-ETO in NIH3T3 cells leads to increased phosphorylation of Ser63 in c-Jun, which is generally JNK dependent. The role of the JNK signaling pathway for the functional properties of AML1-ETO is, however, unknown.
In the present study we found high expression levels of c-jun mRNA in t(8;21), t(15;17) or inv(16) positive patient cells by microarray analysis. Within t(8;21) positive patient samples, there was a correlation between AML1-ETO and c-jun mRNA expression levels. In myeloid U937 cells, c-jun mRNA and c-Jun protein expression levels increased upon induction of AML1-ETO. AML1-ETO transactivated the human c-jun promoter through the proximal AP-1 site via activating the JNK signaling pathway. JNK targets c-Jun and ATF-2, which also bind to the proximal AP-1 site in U937 cells, were also phosphorylated upon AML1-ETO induction. Furthermore, AML1-ETO induction increased the DNA binding capacity of c-Jun and ATF-2 to the proximal AP-1 site of the c-jun promoter, which might result in their enhanced transactivation capacities.
Interference with JNK and c-Jun activation by using JIP-1 or a JNK inhibitor reduced the transactivation capacity of AML1-ETO on the c-jun promoter and the pro-apoptotic function of AML1-ETO in U937 cells. AML1-ETO seems to activate the JNK signaling pathway by inducing the expression of a cytoplasmic factor, possibly G-CSF, because supernatant of AML1-ETO expressing cells was sufficient to induce phosphorylation of JNK and c-Jun in wildtype U937 cells.
This data demonstrates a novel mechanism of how AML1-ETO might exert positive effects on target gene expression and identifies the proto-oncogene c-jun as a common target gene in AML patient cells.Überexpression des Proto-Onkogens c-jun und konstitutive Aktivierung des Jun NH2-terminalen Kinase (JNK)-Signaltransduktionsweges sind wichtig für die leukämische Transformation in der Chronischen Myeloischen Leukämie. Die Expression von c-jun bei Akuter Myeloischer Leukämie (AML) mit den häufigsten reziproken Translokationen ist jedoch unbekannt. Bei einer der häufigsten AML Translokation t(8;21) wurde in Fibroblastenzellen gezeigt, daß das AML1-ETO-Fusionsgen die Phosphorylierung des Serin 63 in c-Jun erhöht. Die Rolle des JNK-Signalweges, der c-Jun am Serin 63 phosphorylieren kann, für die Funktion von AML1-ETO wurde bisher jedoch nicht untersucht. Weiterhin kann aktiviertes c-Jun durch eine positive Rückkoppelungsschleife über den c-jun Promotor zur Erhöhung der c-Jun Expression führen.
In der vorliegenden Arbeit konnten wir zeigen, daß AML Patientenzellen mit den häufigen Translokationen: t(8;21), t(15;17) oder inv(16) mehr c-jun mRNA besitzen im Vergleich zu Knochenmarkszellen gesunder Probanden. Weiterhin fanden wir eine hohe Korrelation zwischen der AML1-ETO und der c-jun mRNA bei t(8;21) positiven Patientenzellen. Induktion von AML1-ETO in der myeloischen U937 Zellinie erhöhte sowohl c-jun mRNA als auch c-Jun Proteinexpression. Damit konnten wir zeigen, daß AML1-ETO die Erhöhung der c-jun Expression bewirkt. Wir untersuchten den molekularen Mechanismus in U937 Zellen mittels transienter Transfektionen und fanden, daß AML1-ETO den c-jun Promotor durch die proximale AP-1 Seite transaktiviert. Diese Transaktivierung erfolgte indirekt über Aktivierung des JNK-Signaltransduktionsweges durch AML1-ETO. AML1-ETO-Induktion führte auch zur Phosphorylierung der JNK-Zielproteine c-Jun und ATF-2. Diese konnten im Gelretardierungsassay an die proximale AP-1 Seite des c-jun Promotors binden und wurden durch AML1-ETO-Induktion in ihrer Bindungsfähigkeit verstärkt. Deshalb nehmen wir an, daß die Transaktivierungskapazität des c-jun Promotors durch AML1-ETO über die Aktivierung des JNK-Signalweges läuft
Boosted charge transfer preamplifier for low power Gbit-scale DRAM
No full textA new charge transfer preamplifier scheme is developed for low power and high, density DRAMs. It employs a boosting method with a MOSFET capacitor for a high voltage precharge level and a pulse control signal for a charge transfer switch. The new scheme increases the sensing margin and enhances the sensing speed under 1.5V operation with a small area overhead. It also leads to a wider design window for a charge transfer switch as the supply voltage scales down
Characterization of Ca-Bi-Mo oxide catalyst for selective propane ammoxidation, using XRD, XPS, TPRX/TPRO, and IR/Raman
No full textThe physicochemical properties of highly active and selective Ca-Bi-Mo oxide for ammoxidation of propane to acrylonitrile were investigated by XRD (powder), IR/Raman, XPS, and TPRX/TPRO (temperature programmed reaction/temperature programmed reoxidation) techniques. It was found that the phases in the Ca-Bi-Mo oxide varied with the composition of the oxide. The modified gamma-bismuth molybdate (gamma-Bi2MoO6) and defective Ca-Bi-Mo phases produced by addition of Bi oxide played an important role in propane ammoxidation to acrylonitrile. XPS results revealed that the mole ratio of elements on the surface was different from that in the bulk. The concentration of bismuth decreased from the surface to the inner layer of CaxTBi2-xMo12 oxide, while the concentration of calcium increased from the surface to the inner layer. The Ca-Bi-Mo oxide showed good catalytic performance when an appropriate amount of calcium oxide was present on the surface along with Bi and Mo oxides. The addition of Ca oxide into Bi-Mo oxide decreased the number of active sites for complete oxidation and increased the ability of reoxidation (O-2 consumption) of reduced catalysts.This research was funded by Tong-Suh
Petrochemical company and CUPS (Center for Ultra-microchemical
Process Systems) sponsored by KOSEF (2003-2004).
The authors thank Professor I. Wachs and Dr. D. S. Kim for
their help in obtaining the Raman spectra
1-Gb/s 80-dB Omega fully differential CMOS transimpedance amplifier in multichip on oxide technology for optical interconnects
No full textA 1-Gb/s differential transimpedance amplifier (TIA) is realized in a 0.25-mum standard CMOS technology, incorporating the regulated cascode input configuration. The TIA chip is then integrated with a p-i-n photodiode on an oxidized phosphorous-silicon (OPS) substrate by employing the multichip-on-oxide (MCO) technology. The NICO TIA demonstrates 80-dBOmega transimpedance gain, 670-MHz bandwidth for 1-pF photodiode capacitance, 0.54-muA average input noise current, -17-dBm sensitivity for 10(-12) bit-error rate (BER), and 27-mW power dissipation from a single 2.5-V supply. It also shows negligible switching noise effect from an embedded VCO on the OPS substrate. Furthermore, a four-channel MCO TIA array is implemented for optical interconnects, resulting in less than -40-dB crosstalk between adjacent channels
Characterization of Ca-Bi-Mo oxide catalyst for propane ammoxidation
No full textThe physicochemical properties of highly active and selective Ca−Bi−Mo oxide for ammoxidation of propane to acrylonitrile were investigated by XRD (powder), IR/Raman, XPS, and TPRX/TPRO (temperature programmed reaction/temperature programmed reoxidation) techniques. It was found that the phases in the Ca−Bi−Mo oxide varied with the composition of the oxide. The modified γ-bismuth molybdate (γ-Bi2MoO6) and defective Ca−Bi−Mo phases produced by addition of Bi oxide played an important role in propane ammoxidation to acrylonitrile. XPS results revealed that the mole ratio of elements on the surface was different from that in the bulk. The concentration of bismuth decreased from the surface to the inner layer of CaxBi12-xMo12 oxide, while the concentration of calcium increased from the surface to the inner layer. The Ca−Bi−Mo oxide showed good catalytic performance when an appropriate amount of calcium oxide was present on the surface along with Bi and Mo oxides. The addition of Ca oxide into Bi−Mo oxide decreased the number of active sites for complete oxidation and increased the ability of reoxidation (O2 consumption) of reduced catalysts
Chosen logistics processes in Škoda JS
No full textThis master thesis deals with the purchase and sale process in Škoda JS company. The aim of this work is to assess whether the setting of the purchase and sale process is met by the company also within a real business case, in compliance with set controls, and whether the degree of perfect delivery is sufficient. In the introduction, the author specifies the basic terms: logistics, logistic chain, customer benefits, information systems in logistics, buying and selling. The following chapter introduces Škoda JS company, including the sphere of its entrepreneurial activity. This chapter also deals with the nuclear power industry. In the crucial chapter, the author describes the process of purchase and sale in Škoda JS company and compares it with a real business case. In conclusion, the author evaluates discrepancies and suggests recommendations to avoid them
Proline-rich tyrosine kinase 2 mediates gonadotropin-releasing hormone signaling to a specific extracellularly regulated kinase-sensitive transcriptional locus in the luteinizing hormone beta-subunit gene
No full textG protein-coupled receptor regulation of gene transcription primarily occurs through the phosphorylation of transcription factors by MAPKs. This requires transduction of an activating signal via scaffold proteins that can ultimately determine the outcome by binding signaling kinases and adapter proteins with effects on the target transcription factor and locus of activation. By investigating these mechanisms, we have elucidated how pituitary gonadotrope cells decode an input GnRH signal into coherent transcriptional output from the LH beta-subunit gene promoter. We show that GnRH activates c-Src and multiple members of the MAPK family, c-Jun NH2-terminal kinase 1/2, p38MAPK, and ERK1/2. Using dominant-negative point mutations and chemical inhibitors, we identified that calcium-dependent proline-rich tyrosine kinase 2 specifically acts as a scaffold for a focal adhesion/cytoskeleton-dependent complex comprised of c-Src, Grb2, and mSos that translocates an ERK-activating signal to the nucleus. The locus of action of ERK was specifically mapped to early growth response-1 (Egr-1) DNA binding sites within the LH beta-subunit gene proximal promoter, which was also activated by p38MAPK, but not c-Jun NH2-terminal kinase 1/2. Egr-1 was confirmed as the transcription factor target of ERK and p38MAPK by blockade of protein expression, transcriptional activity, and DNA binding. We have identified a novel GnRH-activated proline-rich tyrosine kinase 2-dependent ERK-mediated signal transduction pathway that specifically regulates Egr-1 activation of the LH beta-subunit proximal gene promoter, and thus provide insight into the molecular mechanisms required for differential regulation of gonadotropin gene expression
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