A contribution to the knowledge of the skin albuminose cells of Torpedo ocellata Raf [Riv.Istochim.norm.pat. 8 411-416, 1962]

Glandular cells, other than the mucous cells, have been described in the skin of various groups of fish (Teleosts, Ganoids, Selachii) and they have been called 'albuminose' by various authors. The authors propose to study the albuminose cells in the skin of Torpedo ocellata Raf. from a histochemical point of view. The albuminose cells have a complex morphological structure and a correspondingly complicated histochemical make-up. One must treat them as an example of cell with secretions of a particular type, which must and will be better incorporated when more is known of characteristics existent in other species

Effects of butyltins on mitogen-activated-protein kinase kinase kinase and Ras activity in human natural killer cells

Butyltins (BTs) contaminate the environment and are found in human blood. BTs, tributyltin (TBT) and dibutyltin (DBT) diminish the cytotoxic function and levels of key proteins of human natural killer (NK) cells. NK cells are an initial immune defense against tumors, virally infected cells and antibody-coated cells and thus critical to human health. The signaling pathways that regulate NK cell functions include mitogen-activated protein kinases (MAPKs). Studies have shown that exposure to BTs leads to activation of specific MAPKs and MAPK kinases (MAP2Ks) in human NK cells. MAP2K kinases (MAP3Ks) are upstream activators of MAP2Ks, which then activate MAPKs. The current study examined if BT-induced activation of MAP3Ks was responsible for MAP2K and thus, MAPK activation. This study examines the effects of TBT and DBT on the total levels of two MAP3Ks, c-Raf and ASK1, as well as activating and inhibitory phosphorylation sites on these MAP3Ks. In addition, the immediate upstream activator of c-Raf, Ras, was examined for BT-induced alterations. Our results show significant activation of the MAP3K, c-Raf, in human NK cells within 10 min of TBT exposure and the MAP3K, ASK1, after 1 h exposures to TBT. In addition, our results suggest that both TBT and DBT affect the regulation of c-Raf

Lorentz-covariant Hamiltonian analysis of BF gravity with the Immirzi parameter

We perform the Lorentz-covariant Hamiltonian analysis of two Lagrangian action principles that describe general relativity as a constrained BF theory and that include the Immirzi parameter. The relation between these two Lagrangian actions has been already studied through a map among the fields involved. The main difference between these is the way the Immirzi parameter is included, since in one of them the Immirzi parameter is included explicitly in the BF terms, whereas in the other (the CMPR action) it is in the constraint on the B fields. In this work we continue the analysis of their relationship but at the Hamiltonian level. Particularly, we are interested in seeing how the above difference appears in the constraint structure of both action principles. We find that they both possess the same number of first-class and second-class constraints and satisfy a very similar (off-shell) Poisson-bracket algebra on account of the type of canonical variables employed. The two algebras can be transformed into each other by making a suitable change of variablesComment: LaTeX file, no figure

Brominated flame retardants, tetrabromobisphenol A and hexabromocyclododecane, activate mitogen-activated protein kinases (MAPKs) in human natural killer cells

Natural killer (NK) cells provide a vital surveillance against virally infected cells, tumor cells, and antibody-coated cells through the release of cytolytic mediators and gamma interferon (IFN-γ). Hexabromocyclododecane (HBCD) is a brominated flame retardant used primarily in expanded (EPS) and extruded (XPS) polystyrene foams for thermal insulation in the building and construction industry. Tetrabromobisphenol A (TBBPA) is used both as a reactive and an additive flame retardant in a variety of materials. HBCD and TBBPA contaminate the environment and are found in human blood samples. In previous studies, we have shown that other environmental contaminants, such as the dibutyltin (DBT) and tributyltin (TBT), decrease NK lytic function by activating mitogen-activated protein kinases (MAPKs) in the NK cells. HBCD and TBBPA also interfere with NK cell(s) lytic function. The current study evaluates whether HBCD and/or TBBPA have the capacity to activate MAPKs and MAPK kinases (MAP2Ks). The effects of concentrations of HBCD and TBBPA that inhibited lytic function on the phosphorylation state and total levels of the MAPKs (p44/42, p38, and JNK) and the phosphorylation and total levels of the MAP2Ks (MEK1/2 and MKK3/6) were examined. Results indicate that exposure of human NK cells to 10–0.5 μM HBCD or TBBPA activate MAPKs and MAP2Ks. This HBCD and TBBPA-induced activation of MAPKs may leave them unavailable for activation by virally infected or tumor target cells and thus contributes to the observed decreases in lytic function seen in NK cells exposed to HBCD and TBBPA

Temperature dependence of the static and dynamic behaviour in a quenching and partitioning processed low-Si Steel

Because of their excellent combination of strength and ductility, quenching and partitioning (Q & P) steels have a great chance of being added to the third generation of advanced high strength steels. The large ductility of Q & P steels arises from the presence of 10% to 15% of retained austenite which postpones necking due to the transformation induced plasticity (TRIP) effect. Moreover, Q & P steels show promising forming properties with favourable Lankford coefficients, while their planar anisotropy is low due to a weak texture. The stability of the metastable austenite is the key to obtain tailored properties for these steels. To become part of the newest generation of advanced high strength steels, Q & P steels have to preserve their mechanical properties at dynamic strain rates and over a wide range of temperatures. Therefore, in the present study, a low-Si Q & P steel was tested at temperatures from -40 degrees C to 80 degrees C and strain rates from 0.001 s(-1) to 500 s(-1). Results show that the mechanical properties are well-preserved at the lowest temperatures. Indeed, at -40 degrees C and room temperature, no significant loss of the deformation capacity is observed even at dynamic strain rates. This is attributed to the presence of a large fraction of austenite that is so (thermally) stable that it does not transform in the absence of deformation. In addition, the high stability of the austenite decreases the elongation at high test temperatures (80 degrees C). The additional adiabatic heating in the dynamic tests causes the largest reduction of the uniform strain for the samples tested at 80 degrees C. Quantification of the retained austenite fraction in the samples after testing confirmed that, at the highest temperature and strain rate, the TRIP effect is suppressed

Citalopram plus low-dose pipamperone versus citalopram plus placebo in patients with major depressive disorder: an 8-week, double-blind, randomized study on magnitude and timing of clinical response

Background: Selective serotonin reuptake inhibitors take several weeks to achieve their full antidepressant effects. Post-synaptic 5-HT<sub>2A</sub> receptor activation is thought to be involved in this delayed therapeutic effect. Pipamperone acts as a highly selective 5-HT<sub>2A</sub>/D<sub>4</sub> antagonist when administered in low doses. The purpose of this study was to compare citalopram 40 mg once daily plus pipamperone 5 mg twice daily (PipCit) versus citalopram plus placebo twice daily for magnitude and onset of therapeutic effect. Method: An 8-week, randomized, double-blind study in patients with major depressive disorder was carried out. Results: The study population comprised 165 patients (citalopram and placebo, n=82; PipCit, n=83) with a mean baseline Montgomery–Asberg Depression Rating Scale (MADRS) score of 32.6 (S.D.=5.5). In the first 4 weeks, more citalopram and placebo than PipCit patients discontinued treatment (18% v. 4%, respectively, p=0.003). PipCit patients had significantly greater improvement in MADRS score at week 1 [observed cases (OC), p=0.021; last observation carried forward (LOCF), p=0.007] and week 4 (LOCF, p=0.025) but not at week 8 compared with citalopram and placebo patients. Significant differences in MADRS scores favoured PipCit in reduced sleep, reduced appetite, concentration difficulties and pessimistic thoughts. Mean Clinical Global Impression–Improvement scores were significantly improved after 1 week of PipCit compared with citalopram and placebo (OC and LOCF, p=0.002). Conclusions: Although the MADRS score from baseline to 8 weeks did not differ between groups, PipCit provided superior antidepressant effects and fewer discontinuations compared with citalopram and placebo during the first 4 weeks of treatment, especially in the first week

Reflexiones desde la investigación colaborativa en prácticas educativas inclusivas

Como grupo de investigación, hemos recorrido un camino que nos permite no sólo cuestionar teórica y epistemológicamente las concepciones en el campo educativo acerca de los estudiantes, sino también las prácticas que generan un colectivo de estudiantes definidos a priori por su condición de discapacidad/déficit, que reconocidos en su “falta” son direccionados a circuitos escolares poco cualificados.Esta tarea nos posibilita el encuentro con educadores y actores del sistema educativo y nos permite vislumbrar apuestas y realidades acerca de cómo es posible transmutar esos signos negativos en positivos.En el marco del proyecto de investigación planeamos estrategias metodológicas participativas con el objetivo de subjetivar al objeto de estudio y así dar protagonismo a los actores en el escenario educativo otorgándoles voz.Asimismo, intentamos seguir la ruta particular de los estudiantes en los contextos en que se expresan escuchando las demandas y dificultades que se crean y re-crean en el proceso de conocimiento, posibilitando construcciones teóricas cada vez más amplias.Sostenemos que las prácticas innovadoras e inclusivas devienen de un cambio en el modo de nombrar, de concebir a estudiantes con discapacidad. Nos preguntamos acerca de cómo se ha construido la categoría de “alumno/a con discapacidad”, cómo se les ha nombrado social y educativamente y cuáles han sido sus efectos sobre las prácticas.En este sentido, arribamos al concepto de “alumno/a en situación de desventaja educativa”, como un modo de orientar nuestras prácticas y posibilitar una construcción de identidad en el reconocimiento de la singularidad

Microstructural Impact of Si and Ni During High Temperature Quenching and Partitioning Process in Medium-Mn Steels

Austenite stabilization through carbon partitioning from martensite into austenite is an essential aspect of the quenching and partitioning (Q&P) process. Substitutional alloying elements are often included in the chemical composition of Q&P steels to further control the microstructure development by inhibiting carbide precipitation (silicon) and further stabilize austenite (manganese and nickel). However, these elements can interfere in the microstructure development, especially when high partitioning temperatures are considered. In this study, the microstructural development during the Q&P process of four low-carbon, medium-manganese steels with varying contents of silicon and nickel is investigated. During partitioning at 400 °C, silicon hinders cementite precipitation in primary martensite thereby assisting carbon partitioning from martensite to austenite. During partitioning at temperatures of 500 °C and 600 °C, presence of nickel inhibits pearlite formation and promotes austenite reversion, respectively. It is observed that the stabilization of austenite is significantly enhanced through the addition of nickel by slowing down the kinetics of competitive reactions that are stimulated during the partitioning stage. Results of this study provide an understanding of the interplay among carbon, silicon and nickel during Q&P processing that will allow the development of new design strategies to tailor the microstructure of this family of alloys.This research work has been carried out in the framework of the HighQP project (Proposal Number: 709855), funded by the Research Fund for Coal and Steel (RFCS)

Autonomous metabolic reprogramming and oxidative stress characterize endothelial dysfunction in acute myocardial infarction

Background: Compelling evidence has accumulated on the role of oxidative stress on the endothelial cell (EC) dysfunction underlying acute coronary syndrome. However, unveiling the underlying metabolic determinants has been hampered by the scarcity of appropriate cell models to address cell-autonomous mechanisms of ED dysfunction. Methods: We have generated endothelial cells derived from thrombectomy specimens from patients affected with acute myocardial infarction (AMI) and conducted phenotypical and metabolic characterization, focused on central carbon metabolism. Results: AMI-derived endothelial cells (AMIECs), but not control healthy coronary endothelial cells, display impaired growth, migration and tubulogenesis. Metabolically, AMIECs displayed augmented reactive oxygen species (ROS) and glutathione intracellular content, along with a diminished glucose consumption coupled to high lactate production. Consistent with diminished glycolysis in AMIECs, the protein levels of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase type 3, PFKFB3, were downregulated. In contrast, PFKFB4 levels were upregulated, suggesting a shunting of glycolysis towards the pentose phosphate pathway (PPP), supported by upregulation in AMIECs of G6PD, the key enzyme in the oxidative branch of the PPP. Further, the glutaminolytic enzyme GLS was upregulated in AMIECs, providing a mechanistic explanation for the observed increase in glutathione content. Finally, AMIECs displayed a significantly higher mitochondrial membrane potential than control ECs, which, together with high ROS levels, suggest a highly coupled mitochondrial activity in patient ECs. Conclusions: We suggest high mitochondrial proton coupling underlies the abnormally high production of ROS, balanced by PPP- and glutaminolysis-driven synthesis of glutathione, as a primary, cell-autonomous abnormality driving EC dysfunction in AMI. Funding: European Commission Horizon 2020; CIBER- Carlos III National Institute of Health, Spain; Ministerio de Economia y Competitividad (MINECO) and Ministerio de Ciencia e Innovación, Spain; Generalitat de Catalunya-AGAUR, Catalonia; Plataforma Temática Interdisciplinar Salud Global (PTI-SG), Spain; British Heart Foundation, UK. </p