The analysis of Bcr-Abl—Nox signalling in chronic myeloid leukaemia

Chronic Myeloid Leukaemia (CML) is a myeloproliferative disorder characterised by increased proliferation of haematopoietic stem cells. CML results following generation of the chimeric protein Bcr-Abl, a constitutively active tyrosine kinase which induces oncogenesis in part by promoting increased cell survival and proliferation. Since the development of Bcr-Abl-specific tyrosine kinase inhibitors (TKIs) there has been a substantial improvement in the clinical treatment of CML. Unfortunately, residual disease and the development of TKI resistance has become an ever growing concern, resulting in the need for a greater understanding of the disease in order to develop new treatment strategies. Interestingly, constitutive expression of the Bcr-Abl in CML is known to produce elevated levels of Reactive Oxygen Species (ROS) which are known to influence a variety of cellular processes. Previous studies have demonstrated that NADPH oxidase (Nox) activity contributes to intracellular-ROS levels in Bcr-Abl-positive cells, enhancing survival signalling. The objective of this study was to elucidate how Nox protein activity was influenced downstream of Bcr-Abl while examining how Nox-derived ROS influenced CML disease phenotype to identify the potential in targeting these proteins to improve CML treatment. These studies demonstrated that inhibition of Bcr-Abl signalling, led to a significant reduction in ROS levels which was concurrent with the GSK-3dependent, post-translational down-regulation of the small membrane-bound protein p22phox, an essential component of the Nox complex. siRNA knockdown of p22phox identified it to have a significant role in cellular proliferation and cell viability, demonstrating the importance of Nox protein activity in CML disease phenotype. Furthermore, removal of p22phox was demonstrated to make cells significantly more susceptible to Bcr-Abl-specific TKI treatment, while pharmacological silencing of Nox activity in combination with TKIs was demonstrated to produce substantial, synergistic increases in cell death through augmentation of apoptosis, demonstrating the therapeutic potential of targeting Nox proteins in combination with Bcr-Abl inhibition.

Los virus en especies forestales

p.93-98

Análisis genético del cromosoma 5A en dos variedades de trigo

p.199-202

Efectividad de la evaluación de polen en el campo para determinar androesterilidad en maíz (Zea mays ssp. mays)

p.213-220

Algunas consideraciones sobre la selección de híbridos de maíz

p.81-92

Curvularia lunata var., Aeria, nuevo patógeno en semillas de trigo candeal en la Argentina

p.109-112

Conjeturas al realizar una tarea asociada a una ecuación vectorial de la recta con el apoyo de geometría dinámica

En este taller los participantes, a partir del desarrollo de una tarea, identifican algunas etapas en la formulación y validación de conjeturas. La tarea se centra en la exploración de un applet relacionado con la ecuación vectorial de la recta en el plano, a partir del cual se identifican algunas propiedades geométricas del objeto geométrico y, con estas, se establecen e intentan validar generalidades. Este taller surge en el marco del proyecto de investigación “Razonamientos abductivos, inductivos y deductivos desarrollados por estudiantes del curso de Geometría Analítica al realizar una tarea relacionada con la representación de objetos geométricos en distintos sistemas coordenados” que se realiza este año en la Universidad Pedagógica Nacional.

Construcción de la noción de número irracional en formación de profesores: conflictos semióticos y desafíos

La enseñanza y el aprendizaje formalizado de los números irracionales en la formación inicial de profesores de secundaria son problemáticos. Un análisis histórico y epistemológico de la noción de número irracional, sirve de base para enmarcar un estudio empírico, con estudiantes para profesor, que indaga el proceso de construcción de la noción de cardinalidad del conjunto de los números irracionales y la densidad de en R\Q en R. El estudio se realiza por medio de algunos elementos teóricos del enfoque ontosemiótico del conocimiento de y de la instrucción matemáticos. La identificación, por parte del estudiante, de la cardinalidad de conjuntos infinitos, hace posible la emergencia de fenómenos relativos a los cardinales transfinitos, determinándose diferentes tipos de errores y conflictos cognitivos.

Effects of magnetic fields on crystal growth

The effects of a constant uniform magnetic field on thermoelectric currents during dendritic solidification were investigated using an enthalpy based numerical model. It was found that the resulting Lorentz force generates a complex flow influencing the solidification pattern. Experimental work of material processing under high magnetic field conditions has shown that the microstructure can be significantly altered. There is evidence that these effects can be atrtributed to the Lorentz force created through the thermoelectric magentohydrodynamic interactions.[1,2] However the mechanism of how this occurs is not very well understood. In this paper, our aim is to investigate the flow field created from the Lorentz force and how this influences the morphology of dendritic growth for both pure materials and binary alloys.

Low temperature crystal structures of two rhodanine derivatives, 3-amino rhodanine and 3-methyl rhodanine: geometry of the rhodanine ring

Rhodanines (2-thio-4-oxothiazolidines) are synthetic small molecular weight organic molecules with diverse applications in biochemistry, medicinal chemistry, photochemistry, coordination chemistry and industry. The X-ray crystal structure determination of two rhodanine derivatives, namely (I), 3-aminorhodanine [3-amino-2-thio-4-oxothiazolidine], C3H4N2OS2, and (II) 3-methylrhodanine [3-methyl-2-thio-4-oxothiazolidine], C4H5NOS2, have been conducted at 100 K. I crystallizes in the monoclinic space group P2(1)/n with unit cell parameters a = 9.662(2), b = 9.234(2), c = 13.384(2) angstrom, beta = 105.425(3)degrees, V = 1151.1(3) angstrom(3), Z = 8 (2 independent molecules per asymmetric unit), density (calculated) = 1.710 mg/m(3), absorption coefficient = 0.815 mm(-1). II crystallizes in the orthorhombic space group Iba2 with unit cell a = 20.117(4), b = 23.449(5), c = 7.852(2) angstrom, V = 3703.9(12) angstrom(3), Z = 24 (three independent molecules per asymmetric unit), density (calculated) = 1.584 mg/m(3), absorption coefficient 0.755 mm(-1). For I in the final refinement cycle the data/restraints/parameter ratios were 2639/0/161, goodness-of-fit on F-2 = 0.934, final R indices [I > 2sigma(I)] were R1 = 0.0299, wR2 = 0.0545 and R indices (all data) R1 = 0.0399, wR2 = 0.0568. The largest difference peak and hole were 0.402 and -0.259 e angstrom(-3). For II in the final refinement cycle the data/restraints/parameter ratios were 3372/1/221, goodness-of-fit on F(2) = 0.950, final R indices [I > 2sigma(I)] were R1 = 0.0407, wR2 = 0.1048 and R indices (all data) R1 = 0.0450, wR2 = 0.1088. The absolute structure parameter = 0.19(9) and largest difference peak and hole 0.934 and -0.301 e angstrom(-3). Details of the geometry of the five molecules (two for I and three for II) and the crystal structures are fully discussed. Corresponding features of the molecular geometry are highly consistent and firmly establish the geometry of the rhodanine

Floristic notes of Sierra del Rincón Biosphere Reserve (Spain, Madrid province)

New records of vascular plants from Sierra del Rincón Biosphere Reserve and surroundings (Spain, Madrid province) are provided. It is noteworthy the presence of atlantic flora in this continental area and the different shrubby communities in different sectors with different litology: in areas with gneiss they are dominated by leguminous genisteae; where it is schistous, shale or quartzite they are heathlands.