Crostas ferromanganíferas do atlântico central

A exploração dos montes submarinos a sul dos Açores na campanha EMEPC/Açores/G3/2007 permitiu a recolha de 30 crostas ferromanganíferas nos montes submarinos Atlantis, Great Meteor, Small Hyeres, Irving, Plato e ainda na Zona da Fratura Leste dos Açores. Estas foram as primeiras amostras de crostas de Fe-Mn recolhidas nestes montes. As crostas de Fe-Mn foram analisadas utilizando vários métodos analíticos. Texturalmente as crostas são bastante homogéneas, mostrando as texturas típicas deste tipo de ocorrências. A razão Fe/Mn, os padrões e concentrações de terras raras, e a grande homogeneidade das crostas permite afirmar que todas elas são de origem hidrógena, precipitando lentamente a partir da água do mar. Embora o conteúdo em Fe e Mn das crostas seja consistente com os dados disponíveis para o Atlântico, a concentração média de Co é comparável aos valores médios do Pacífico. O Cu e o Ni apresentam valores inferiores aos deste oceano; ABSTRACT: The exploration of seamounts south of the Azores during the EMEPC/Açores/G3/2007 campaign allowed the collection of 30 Fe-Mn crusts from the Atlantis, Great Meteor, Small Hyeres, Irving and Plato seamounts, as well as from the East Azores Fracture Zone. These were the first samples of Fe-Mn crusts studied for these seamounts. The Fe-Mn crusts were analyzed using multiple analytical methods. The crusts are fairly homogeneous, showing typical textures for this type of occurrences. The Fe/Mn ratio, patterns and concentrations in rare earth elements, and the great homogeneity of the crusts lead to the conclusion that they have a hydrogenetic origin, precipitating directly from the seawater. Although the content in Fe and Mn of the crusts is consistent with data available for the Atlantic, the mean concentration of Co is comparable to the average values for the Pacific. Cu and Ni show lower values than the ones known for the Pacific

ROS production is essential for the apoptotic function of E2F1 in pheochromocytoma and neuroblastoma cell lines

In this study we demonstrate that accumulation of reactive oxygen species (ROS) is essential for E2F1 mediated apoptosis in ER-E2F1 PC12 pheochromocytoma, and SH-SY5Y and SK-N-JD neuroblastoma stable cell lines. In these cells, the ER-E2F1 fusion protein is expressed in the cytosol; the addition of 4-hydroxytamoxifen (OHT) induces its translocation to the nucleus and activation of E2F1target genes. Previously we demonstrated that, in ER-E2F1 PC12 cells, OHT treatment induced apoptosis through activation of caspase-3. Here we show that caspase-8 activity did not change upon treatment with OHT. Moreover, over-expression of Bcl-xL arrested OHT-induced apoptosis; by contrast, over-expression of c-FLIP, did not have any effect on OHT-induced apoptosis. OHT addition induces BimL expression, its translocation to mitochondria and activation of Bax, which is paralleled by diminished mitochondrial enrichment of Bcl-xL. Treatment with a Bax-inhibitory peptide reduced OHT-induced apoptosis. These results point out the essential role of mitochondria on the apoptotic process driven by E2F1. ROS accumulation followed E2F1 induction and treatment with the antioxidant N-acetylcysteine, inhibited E2F1-induced Bax translocation to mitochondria and subsequent apoptosis. The role of ROS in mediating OHT-induced apoptosis was also studied in two neuroblastoma cell lines, SH-SY5Y and SK-N-JD. In SH-SY5Y cells, activation of E2F1 by the addition of OHT induced ROS production and apoptosis, whereas over-expression of E2F1 in SK-N-JD cells failed to induce either response. Transcriptional profiling revealed that many of the genes responsible for scavenging ROS were down-regulated following E2F1-induction in SH-SY5Y, but not in SK-N-JD cells. Finally, inhibition of GSK3β blocked ROS production, Bax activation and the down regulation of ROS scavenging genes. These findings provide an explanation for the apparent contradictory role of E2F1 as an apoptotic agent versus a cell cycle activator

Sorafenib sensitizes hepatocellular carcinoma cells to physiological apoptotic stimuli

Sorafenib increases survival rate of patients with advanced hepatocellular carcinoma (HCC). The mechanism underlying this effect is not completely understood. In this work we have analyzed the effects of sorafenib on autocrine proliferation and survival of different human HCC cell lines. Our results indicate that sorafenib in vitro counteracts autocrine growth of different tumor cells (Hep3B, HepG2, PLC-PRF-5, SK-Hep1). Arrest in S/G2/M cell cycle phases were observed coincident with cyclin D1 down-regulation. However, sorafenib's main anti-tumor activity seems to occur through cell death induction which correlated with caspase activation, increase in the percentage of hypodiploid cells, activation of BAX and BAK and cytochrome c release from mitochondria to cytosol. In addition, we observed a rise in mRNA and protein levels of the pro-apoptotic BH3-domain only PUMA and BIM, as well as decreased protein levels of the anti-apoptotic MCL1 and survivin. PUMA targeting knock-down, by using specific siRNAs, inhibited sorafenib-induced apoptotic features. Moreover, we obtained evidence suggesting that sorafenib also sensitizes HCC cells to the apoptotic activity of transforming growth factor-beta (TGF-beta) through the intrinsic pathway and to tumor necrosis factor-a (TNF) through the extrinsic pathway. Interestingly, sensitization to sorafenib-induced apoptosis is characteristic of liver tumor cells, since untransformed hepatocytes did not respond to sorafenib inducing apoptosis, either alone or in combination with TGF-beta or TNF. Indeed, sorafenib effectiveness in delaying HCC late progression might be partly related to a selectively sensitization of HCC cells to apoptosis by disrupting autocrine signals that protect them from adverse conditions and pro-apoptotic physiological cytokines. J. Cell. Physiol. 227: 1319-1325, 2012. (C) 2011 Wiley Periodicals, Inc

Guia d'actuacions docents universitàries sobre gènere i prevenció de violència de gènere

Aquesta guia és producte del projecte “Prevenció de les violències de gènere des d’una formació basada en evidències científiques” finançat per l’Agència de Gestió d'Ajuts Universitaris i de Recerca (AGAUR) dins dels d’ajuts per a projectes d'innovació per a la millora de la qualitat docent en matèria de violència de gènere (2021 INDOV 0008)Aquest projecte ha contribuït en l'avenç en l'erradicació de la violència de gènere en l'àmbit universitari, a partir de la formació integral de futures i futurs professionals. Aquest objectiu ha estat assolit a través de la creació i consolidació d'entorns de tolerància zero cap la violència i lliures de la mateixa. De forma transversal i al llarg de tot el desenvolupament del projecte, s'ha emfatitzat el reconeixement d’altres formes de violència de gènere fora del context de les parelles. De manera més concreta, a través de les innovacions educatives basades en evidències científiques, seguint la línia de recerca de socialització preventiva de la violència de gènere, el projecte ha dut a terme tasques de sensibilització envers la problemàtica dins l'àmbit universitari, tot aportant a les aules la reflexió respecte factors d'incidència en la violència de gènere o la construcció de les identitats de gènere, entre d'altres. Per fer-ho s'han dut a terme activitats com la lectura de textos científics sobre gènere i prevenció de la violència de gènere, la creació d'espais pel diàleg i el debat, la col·laboració d'actors socials relacionats amb la realitat de la violència de gènere i la incorporació d'eines tecnològiques per a facilitar la construcció de coneixement relacionat amb la prevenció de la violència de gènere. En aquest sentit, s'han donat a conèixer eines d'utilitat que els hi permeten accedir i participar en la construcció de coneixement sobre la temàtica, com és el cas de la plataforma "Sappho". Tot aquest coneixement ha quedat recollit en un document de recomanacions per la docència universitària compromesa en la lluita contra la violència de gènere

NADPH oxidase NOX1 controls autocrine growth of liver tumor cells through up-regulation of the epidermal growth factor receptor pathway

FaO rat hepatoma cells proliferate in the absence of serum through a mechanism that requires activation of the epidermal growth factor receptor (EGFR) pathway. The aim of this work was to analyze the molecular mechanisms that control EGFR activation in these and other liver tumor cells. Reactive oxygen species production is observed a short time after serum withdrawal in FaO cells, coincident with up-regulation of the NADPH oxidase NOX1. NOX1-targeted knockdown, the use of antioxidants, or pharmacological inhibition of NADPH oxidase attenuates autocrine growth, coincident with lower mRNA levels of EGFR and its ligand transforming growth factor-alpha (TGF-alpha) and a decrease in phosphorylation of EGFR. EGFR-targeted knockdown induces similar effects on cell growth and downstream signals to those observed in NOX1-depleted cells. Early NOX1 activation induces both a feedback-positive loop via an Src-ERK pathway that up-regulates its own levels, and a parallel signaling pathway through p38 MAPK and AKT resulting in EGFR and TGF-alpha up-regulation. Human hepatocellular carcinoma cell lines, but not non-tumoral hepatocytes, show autocrine growth upon serum withdrawal, which is also coincident with NOX1 up-regulation that mediates EGFR and TGF-alpha expression. The use of antioxidants, or pharmacological inhibition of NADPH oxidase, effectively attenuates autocrine growth in hepatocellular carcinoma cell lines. In summary, results presented in this study indicate that NOX1 might control autocrine cell growth of liver tumor cells through regulation of the EGFR pathway

Protein-tyrosine phosphatase 1B (PTP1B) deficiency confers resistance to transforming growth factor-β (TGF-β)-induced suppressor effects in hepatocytes

Transforming growth factor-β (TGF-β) plays a dual role in hepatocytes, mediating both tumor suppressor and promoter effects. The suppressor effects of the cytokine can be negatively regulated by activation of survival signals, mostly dependent on tyrosine kinase activity. The aim of our work was to study the role of the protein-tyrosine phosphatase 1B (PTP1B) on the cellular responses to TGF-β, using for this purpose immortalized neonatal hepatocytes isolated from both PTP1B(+/+) and PTP1B(-/-) mice. We have found that PTP1B deficiency conferred resistance to TGF-β suppressor effects, such as apoptosis and growth inhibition, correlating with lower Smad2/Smad3 activation. Both responses were recovered in the presence of the general tyrosine kinase inhibitor genistein. PTP1B(-/-) cells showed elevated NF-κB activation in response to TGF-β. Knockdown of the NF-κB p65 subunit increased cell response in terms of Smads phosphorylation and apoptosis. Interestingly, these effects were accompanied by inhibition of Smad7 up-regulation. In addition, lack of PTP1B promoted an altered NADPH oxidase (NOX) expression pattern in response to TGF-β, strongly increasing the NOX1/NOX4 ratio, which was reverted by genistein and p65 knockdown. Importantly, NOX1 knockdown inhibited nuclear translocation of p65, promoted Smad phosphorylation, and decreased Smad7 levels. In summary, our results suggest that PTP1B deficiency confers resistance to TGF-β through Smad inhibition, an effect that is mediated by NOX1-dependent NF-κB activation, which in turn, increases the level of the Smad inhibitor Smad7 and participates in a positive feedback loop on NOX1 up-regulation

NADPH oxidase NOX4 mediates stellate cell activation and hepatocyte cell death during liver fibrosis development.

A role for the NADPH oxidases NOX1 and NOX2 in liver fibrosis has been proposed, but the implication of NOX4 is poorly understood yet. The aim of this work was to study the functional role of NOX4 in different cell populations implicated in liver fibrosis: hepatic stellate cells (HSC), myofibroblats (MFBs) and hepatocytes. Two different mice models that develop spontaneous fibrosis (Mdr2−/−/p19ARF−/−, Stat3Δhc/Mdr2−/−) and a model of experimental induced fibrosis (CCl4) were used. In addition, gene expression in biopsies from chronic hepatitis C virus (HCV) patients or non-fibrotic liver samples was analyzed. Results have indicated that NOX4 expression was increased in the livers of all animal models, concomitantly with fibrosis development and TGF-β pathway activation. In vitro TGF-β-treated HSC increased NOX4 expression correlating with transdifferentiation to MFBs. Knockdown experiments revealed that NOX4 downstream TGF-β is necessary for HSC activation as well as for the maintenance of the MFB phenotype. NOX4 was not necessary for TGF-β-induced epithelial-mesenchymal transition (EMT), but was required for TGF-β-induced apoptosis in hepatocytes. Finally, NOX4 expression was elevated in patients with hepatitis C virus (HCV)-derived fibrosis, increasing along the fibrosis degree. In summary, fibrosis progression both in vitro and in vivo (animal models and patients) is accompanied by increased NOX4 expression, which mediates acquisition and maintenance of the MFB phenotype, as well as TGF-β-induced death of hepatocytes

ROS production is essential for the apoptotic function of E2F1 in pheochromocytoma and neuroblastoma cell lines

In this study we demonstrate that accumulation of reactive oxygen species (ROS) is essential for E2F1 mediated apoptosis in ER-E2F1 PC12 pheochromocytoma, and SH-SY5Y and SK-N-JD neuroblastoma stable cell lines. In these cells, the ER-E2F1 fusion protein is expressed in the cytosol; the addition of 4-hydroxytamoxifen (OHT) induces its translocation to the nucleus and activation of E2F1target genes. Previously we demonstrated that, in ER-E2F1 PC12 cells, OHT treatment induced apoptosis through activation of caspase-3. Here we show that caspase-8 activity did not change upon treatment with OHT. Moreover, over-expression of Bcl-xL arrested OHT-induced apoptosis; by contrast, over-expression of c-FLIP, did not have any effect on OHT-induced apoptosis. OHT addition induces BimL expression, its translocation to mitochondria and activation of Bax, which is paralleled by diminished mitochondrial enrichment of Bcl-xL. Treatment with a Bax-inhibitory peptide reduced OHT-induced apoptosis. These results point out the essential role of mitochondria on the apoptotic process driven by E2F1. ROS accumulation followed E2F1 induction and treatment with the antioxidant N-acetylcysteine, inhibited E2F1-induced Bax translocation to mitochondria and subsequent apoptosis. The role of ROS in mediating OHT-induced apoptosis was also studied in two neuroblastoma cell lines, SH-SY5Y and SK-N-JD. In SH-SY5Y cells, activation of E2F1 by the addition of OHT induced ROS production and apoptosis, whereas over-expression of E2F1 in SK-N-JD cells failed to induce either response. Transcriptional profiling revealed that many of the genes responsible for scavenging ROS were down-regulated following E2F1-induction in SH-SY5Y, but not in SK-N-JD cells. Finally, inhibition of GSK3β blocked ROS production, Bax activation and the down regulation of ROS scavenging genes. These findings provide an explanation for the apparent contradictory role of E2F1 as an apoptotic agent versus a cell cycle activator

Sorafenib sensitizes hepatocellular carcinoma cells to physiological apoptotic stimuli

Sorafenib increases survival rate of patients with advanced hepatocellular carcinoma (HCC). The mechanism underlying this effect is not completely understood. In this work we have analyzed the effects of sorafenib on autocrine proliferation and survival of different human HCC cell lines. Our results indicate that sorafenib in vitro counteracts autocrine growth of different tumor cells (Hep3B, HepG2, PLC-PRF-5, SK-Hep1). Arrest in S/G2/M cell cycle phases were observed coincident with cyclin D1 down-regulation. However, sorafenib's main anti-tumor activity seems to occur through cell death induction which correlated with caspase activation, increase in the percentage of hypodiploid cells, activation of BAX and BAK and cytochrome c release from mitochondria to cytosol. In addition, we observed a rise in mRNA and protein levels of the pro-apoptotic BH3-domain only PUMA and BIM, as well as decreased protein levels of the anti-apoptotic MCL1 and survivin. PUMA targeting knock-down, by using specific siRNAs, inhibited sorafenib-induced apoptotic features. Moreover, we obtained evidence suggesting that sorafenib also sensitizes HCC cells to the apoptotic activity of transforming growth factor-beta (TGF-beta) through the intrinsic pathway and to tumor necrosis factor-a (TNF) through the extrinsic pathway. Interestingly, sensitization to sorafenib-induced apoptosis is characteristic of liver tumor cells, since untransformed hepatocytes did not respond to sorafenib inducing apoptosis, either alone or in combination with TGF-beta or TNF. Indeed, sorafenib effectiveness in delaying HCC late progression might be partly related to a selectively sensitization of HCC cells to apoptosis by disrupting autocrine signals that protect them from adverse conditions and pro-apoptotic physiological cytokines. J. Cell. Physiol. 227: 1319-1325, 2012. (C) 2011 Wiley Periodicals, Inc