2,613,017 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
Transient outward K+ current (ITO) reduction prolongs action potentials and promotes afterdepolarisations: a dynamic-clamp study in human and rabbit cardiac atrial myocytes
No full textBackground and aim: Human atrial transient outward K+ current (ITO) is decreased in a variety of cardiac pathologies, but how ITO reduction alters action potentials (AP) and arrhythmia mechanisms is poorly understood, owing to non-selectivity of ITO blockers.<p></p>
Aim: to investigate effects of selective ITO changes on AP shape and duration (APD), and on afterdepolarisations or abnormal automaticity with beta-adrenergic-stimulation, using the dynamic-clamp technique in atrial cells.<p></p>
Methods and Results: Human and rabbit atrial cells were isolated by enzymatic dissociation, and electrical activity recorded by whole-cell-patch clamp (35-37oC). Dynamic-clamp-simulated ITO reduction or block slowed AP phase 1 and elevated the plateau, significantly prolonging APD, in both species. In human atrial cells, ITO block (100% ITO subtraction) increased APD50 by 31%, APD90 by 17%, and APD-61mV (reflecting cellular effective refractory period) by 22% (P<0.05 for each). Interrupting ITO block at various time points during repolarisation revealed that the APD90 increase resulted mainly from plateau-elevation, rather than from phase 1-slowing or any residual ITO. In rabbit atrial cells, partial ITO block (~40% ITO subtraction) reversibly increased the incidence of cellular arrhythmic depolarisations (CADs; afterdepolarisations and/or abnormal automaticity) in the presence of the beta-agonist isoproterenol (0.1 μM; ISO), from 0% to 64% (P<0.05). ISO-induced CADs were significantly suppressed by dynamic-clamp increase in ITO (~40% ITO addition). ISO+ITO decrease-induced CADs were abolished by beta1-antagonism with atenolol at therapeutic concentration (1 μM).<p></p>
Conclusion. Atrial cell action potential changes from selective ITO modulation, shown for the first time using dynamic-clamp, have the potential to influence reentrant and non-reentrant arrhythmia mechanisms, with implications for both the development and treatment of atrial fibrillation
C/EBPalpha downregualtes c-jun expression
No full textThe transcription factor C/EBPa is crucial for the differentiation of granulocytes. Conditional expression of C/EBPa triggers neutrophilic differentiation and C/EBPa can block TPA induced monocytic differentiation of bipotential myeloid cells. In C/EBPa knockout mice, no mature granulocytes are present. A dramatic increase of c-jun mRNA in C/EBPa knockout mice fetal liver was observed. c-jun, a component of the AP-1 transcription factor complex and a co-activator of the transcription factor PU.1, is important for monocytic differentiation. Here we report that C/EBPa downregulates c-jun expression to drive granulocytic differentiation. Ectopic increase of C/EBPa expression decreases c-jun mRNA level, and the human c-jun promoter activity is downregulated 8 fold in presence of C/EBPa. C/EBPa and c-jun interact through their leucine zipper domains and this interaction prevents c-jun from binding to DNA. This results in downregulation of c-jun’s capacity to autoregulate its own promoter through the proximal AP-1 site. Overexpression of c-jun prevents C/EBPa induced granulocytic differentiation. c-jun expression was higher in AML M2 patients with dominant negative C/EBPa mutations in comparison to AML M2 patients without C/EBPa mutations. Thus, we propose a model in which C/EBPa needs to downregulate c-jun expression and transactivation capacity for promoting granulocytic differentiation.Der Transkriptionsfaktor C/EBPa ist essentiell für die Differenzierung von Granulozyten. Die konditionelle Expression von C/EBPa induziert die neutrophile Differenzierung. Überdies kann C/EBPa die TPA-induzierte Differenzierung von myeloiden Vorläuferzellen zu Monozyten blockieren. In C/EBPa knockout Mäusen gibt es keine reifen Granulozyten. In der fötalen Leber von C/EBPa knockout Mäusen konnte eine stark erhöhte Expression der c-jun mRNA beobachtet werden. c-jun ist eine Komponente des AP-1 Transkriptionsfaktorkomplexes, ein Koaktivator des Transkriptionsfaktors PU.1 und ist wichtig für die Differenzierung von Monozyten. In dieser Arbeit zeigen wir, dass C/EBPa die c-jun Expression herunterreguliert und somit die Differenzierung von Granulozyten induziert. Die Überexpression von C/EBPa reduzierte die c-jun mRNA Menge und die Aktivität des humanen c-jun Promotors war in der Gegenwart von C/EBPa 8-fach herunterreguliert. C/EBPa und c-jun interagieren über ihre Leucin-Zipper Domänen und diese Interaktion verhindert die DNA-Bindung von c-jun. Dies resultiert in einer verminderten Kapazität von c-jun, den eigenen Promotor über die proximale AP-1 Stelle zu regulieren. Die Überexpression von c-jun blockiert die durch C/EBPa induzierte granulozytäre Differenzierung. Die c-jun Expression war in AML-M2 Patienten mit dominant-negativen Mutationen in C/EBPa im Vergleich zu AML-M2 Patienten ohne Mutationen in C/EBPa erhöht. Aufgrund dieser Daten schlagen wir ein Modell vor, in dem C/EBPa die Expression und Transaktivierungskapazität von c-jun herunterregulieren muß, um die granulozytäre Differenzierung zu induzieren
Método potenciodinâmico aplicado ao estudo da difusão iônica limitada por camada porosa em substratos de ITO
No full textDissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Ciências Físicas e Matemáticas, Programa de Pós-Graduação em Física, Florianópolis, 2013.Esta dissertação tem como objetivo estudar o comportamento do substrato transparente condutor composto por óxido de índio dopado com estanho (ITO) durante tratamento catódico em eletrólitos inertes de NaCl, KCl, KI e AlCl3, em diferentes concentrações possuindo a mesma força iônica e em seu pH natural. Após o tratamento é observada a formação de partículas esféricas metálicas de In-Sn, decorrentes da redução do ITO. A morfologia dos depósitos varia com o eletrólito usado e com a velocidade do processo de redução. Os resultados obtidos através dos estudos potenciodinâmicos dos eletrodos indicam um processo controlado por resistência ôhmica. O comportamento resistivo observado durante a formação da camada porosa metálica sugere a aplicação do modelo de resistência de camada porosa LPRM (do inglês Layer-Pore Resistance Model) para análise do processo. No entanto, o modelo LPRM, na forma como foi originalmente desenvolvido, não descreve bem o processo. Uma modificação ao modelo é proposta, a partir da qual, logra-se obter bons ajustes do modelo às curvas potenciodinâmicas. O conjunto de parâmetros extraído do ajuste de curvas obtidas com diferentes taxas de varredura mostra boa correlação com o crescimento da camada porosa e pode ser interpretado como uma medida do caminho difusivo que os íons do eletrólito necessitam percorrer para atingir a camada de ITO subjacente. A modificação da morfologia do substrato durante o processo de redução catódica foi caracterizada por microscopia eletrônica de varredura (MEV) e microscopia de força atômica (AFM). Da análise da rugosidade superficial, obtida das micrografias de AFM, extraiu-se o comprimento de correlação, que mede a granularidade da camada porosa. Usando conceitos simples de passeio aleatório, foi possível estabelecer uma relação entre o caminho difusivo iônico determinado eletroquimicamente, e a morfologia da camada porosa, para os diferentes eletrólitos utilizados.Abstract : This work investigates the behavior of transparent conducting substrates composed of indium tin oxide (ITO) during cathodic treatment in inert aqueous electrolytes (NaCl, KCl, KI e AlCl3), using different concentrations with same ionic force. The treatment causes the formation of spherical metallic particles of In-Sn, resulting from ITO reduction. It is possible to observe that the morphology of deposits is affected by the electrolyte composition and sweep rate. Potentiodynamic studies indicate a process controlled by Ohmic resistance. The resistive behavior observed during growth of the porous metallic layer suggests the application of the Layer-Pore Resistance Model (LPRM) to analyze the results. However, the LPRM model, in its original form, does not give a good description of the process. A modified version of the LPRM is proposed, which yields very good fits to the potentiodynamic curves. The set of fit parameters extracted from the curves, obtained at different scan rates, shows a good correlation with the growth of the porous layer, and could be interpreted as a measure of diffusion paths that ions must travel to reach the underlying ITO layer. The changes on morphology of the substrates during the cathodic reduction was characterized by scanning electron microscope (SEM) and atomic force microscope (AFM). From the roughness analysis obtained from the AFM micrographs, a correlation length was determined that describes the granularity of the porous layer. Using simple concepts of random walk, it was possible to establish a relationship between the ionic diffusion path determined electrochemically, and the morphology of porous layer, for the different electrolytes used
Proto-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
P-n Junction Formation in ITO/p-Si Structure by Powerful Laser Radiation for Solar Cells Applications
No full textThe research report is devoted to the development of a new method of nanostructures formation in ITO/p-Si/Al structure with powerful laser radiation and study of its optical and electrical properties for solar cells applications. It was shown that after the structure irradiation by Nd:YAG laser second harmonic, dark current voltage characteristics become diode-like. Increase of ITO/p-Si/Al solar cell efficiency after irradiation by the laser, using photocurrent voltage
characteristic method, was shown
Hydroptila nanseiensis Ito 2011
No full textHydroptila nanseiensis Ito 2011, in Ito et al. 2011 (Fig. 6) Hydroptila nanseiensis Ito 2011, in Ito et al. 2011, 14–15, male, female, Japan (Ryukyu).Published as part of Ito, Tomiko, 2021, Descriptions of final instar larvae of six species of the genus Hydroptila Dalman (Trichoptera, Hydroptilidae) in Japan, pp. 339-350 in Zootaxa 4915 (3) on page 347, DOI: 10.11646/zootaxa.4915.3.3, http://zenodo.org/record/445649
Bonding InGaAsP/ITO/Si Hybrid Laser With ITO as Cathode and Light-Coupling Material
No full textA 1.5-mu m InGaAsP/ITO/Si hybrid laser with indium tin oxide (ITO) as both a cathode and a light-coupling material is presented. The InGaAsP gain structure with a transparent ITO cathode is flip-chip bonded onto a patterned silicon-on-insulator wafer. The light generated in the InGaAsP multiquantum wells is coupled through the ITO cathode into the Si waveguide to form an InGaAsP/ITO/Si hybrid laser. The threshold current density of this hybrid laser is 20 kA/cm(2) at 210 K. Due to the advantages of post-bonding and simplicity of the fabrication process, such a hybrid laser may be a promising Si light source.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000302534300023&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701Engineering, Electrical & ElectronicOpticsPhysics, AppliedSCI(E)EI14ARTICLE8712-7142
Signaling through CD44 affects cell cycle progression and c-Jun expression in acute myeloid leukemia cells
No full textWe present here the first evidence linking CD44 signaling to c-Jun expression and cell cycle progression in myeloid cell line models. CD44 ligation with the anti-CD44 monoclonal antibodies have been shown to induce differentiation and inhibit the proliferation of human acute myeloid leukemia (AML) cells, and c-Jun is involved in the regulation of these processes. The effects of anti-CD44 monoclonal antibody A3D8, on myeloid cells were associated with specific disruption of cell cycle events and induction of G0/G1 arrest. Induction of G0/G1 arrest was accompanied by an increase in the expression of p21, attenuation of pRb phosphorylation and associated with decreased CDK2 and CDK4 kinase activities. We observed that A3D8 treatment of AML patient blasts and HL60/U937 cells led to the downregulation of c-Jun expression at mRNA and protein level. Transient transfection studies showed the inhibition of c-jun promoter activity by A3D8, involving both AP-1 sites. Furthermore, A3D8 treatment caused a decrease in JNK protein expression and a decrease in the level of phosphorylated c-Jun. Ectopic overexpression of c-Jun in HL60 cells was able to induce proliferation and prevent the anti-proliferative effects of A3D8. Targeting of G1 regulatory proteins and the resulting induction of G1 arrest by A3D8 may provide new insights into anti-proliferative and differentiation therapy of AML
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