Simultaneous inhibition of pan-phosphatidylinositol-3-kinases and MEK as a potential therapeutic strategy in peripheral T-cell lymphomas

Obtained from Haematologica/the Hematology Journal website http://www.haematologica.orgPeripheral T-cell lymphomas are very aggressive hematologic malignancies for which there is no targeted therapy. New, rational approaches are necessary to improve the very poor outcome in these patients. Phosphatidylinositol- 3-kinase is one of the most important pathways in cell survival and proliferation. We hypothesized that phosphatidylinositol- 3-kinase inhibitors could be rationally selected drugs for treating peripheral T-cell lymphomas. Several phosphatidylinositol-3-kinase isoforms were inhibited genetically (using small interfering RNA) and pharmacologically (with CAL-101 and GDC-0941 compounds) in a panel of six peripheral and cutaneous T-cell lymphoma cell lines. Cell viability was measured by intracellular ATP content; apoptosis and cell cycle changes were checked by flow cytometry. Pharmacodynamic biomarkers were assessed by western blot. The PIK3CD gene, which encodes the δ isoform of phosphatidylinositol-3-kinase, was overexpressed in cell lines and primary samples, and correlated with survival pathways. However, neither genetic nor specific pharmacological inhibition of phosphatidylinositol-3-kinase δ affected cell survival. In contrast, the pan-phosphatidylinositol-3-kinase inhibitor GDC-0941 arrested all T-cell lymphoma cell lines in the G1 phase and induced apoptosis in a subset of them. We identified phospho-GSK3b and phospho-p70S6K as potential biomarkers of phosphatidylinositol-3-kinase inhibitors. Interestingly, an increase in ERK phosphorylation was observed in some GDC-0941-treated T-cell lymphoma cell lines, suggesting the presence of a combination of phosphatidylinositol-3-kinase and MEK inhibitors. A highly synergistic effect was found between the two inhibitors, with the combination enhancing cell cycle arrest at G0/G1 in all T-cell lymphoma cell lines, and reducing cell viability in primary tumor T cells ex vivo. These results suggest that the combined treatment of pan-phosphatidylinositol-3-kinase + MEK inhibitors could be more effective than single phosphatidylinositol-3-kinase inhibitor treatment, and therefore, that this combination could be of therapeutic value for treating peripheral and cutaneous T-cell lymphomas.This work was supported by grants from the Asociación Española Contra el Cáncer, Fondo de Investigaciones Sanitarias (PI051623, PI052800 and PI080856), RTICC (RD06/0020/0107) and Ministerio de Ciencia e Innovación (SAF2008-0387-1). EMS is supported by a grant from the Department of Education, Universities and Research of the Basque Government (BFI08.207). MSB is supported by a Contract Miguel Servet from Fondo de Investigaciones Sanitarias (CP11/00018

Revista de Vertebrados de la Estación Biológica de Doñaña

Comportamiento reproductor del camaleón común (Chamaeleo chamaeleon L.) en el sur de EspañaDistribución de los reptiles en la provincia de Granada (SE. Península Ibérica)Datos sobre la reproducción y el crecimientode Psammodromus hispanicus Fitzinger, 1826 en un medio adehesado de la España CentralVariación en la colocación y orientación del nido del Alzacola (Cercotrichas galactotes) en dos especies de árbolesOrganización de la comunidad de aves reproductora en las landas montanas del País Vasco AtlánticoEcología de una población ibérica de lobos (Canis Lupus)Etude biométrique des Crosidures (Soricidae, Insectivora) de la región de Massa (Souss, Maroe).Variación geográfica del género Eliomys en la Península IbéricaTendencias gregarias del Ciervo (Cervus elaphus) en Doñana.Data on the autumn diet of the red deer (Cervus elaphus L. 1758) in the Montes de Toledo (Central Spain)Nota sobre la coexistencia de Hyla arborea (L. 1758E Hyla meridionalis (Boettger 1874) rn rl Valle del TiétarCalendario reproductivo y tamaño de las puesta en el galápago leproso, Mauremys leprosa (Shweigger, 1812), en Doñana, HuelvaPelícola (Felicola) inaqualis Piager, 1880 (MALLOPHAGA:TRICHODECTIDAE) parásito deE Herpestes ichneumon L (CARNIVORA: HERPESTIDAE)Abundancia y amplitud de los desplazamientos de Apodemus sylvaticus en cuatro biotopos de Doñana que difieren en cobertura vegetalPeer reviewe

Marker development for quality protein maize breeding and an interaction study between Opaque-2 and Ask2 genes

Quality Protein Maize (QPM) kernels contain twice the amounts of lysine and tryptophan compared to normal corn kernels. Although the opaque-2 (o2) mutation is the underlying cause of this beneficial change, other genes such as Aspartate kinase-2 (Ask2) affect the amino acid content in the endosperm to a lesser degree. To date, reports on the interaction between both loci are scarce and there are no high-throughput assays for the identification of the alleles of these genes. The objectives of this research were: 1) to study the interaction between the o2 and Ask2 genes with respect to the accumulation of amino acids in the endosperm in an F2 population, 2) to identify conserved SNPs into the o2 gene that can be used as markers, 3) to estimate the frequency of an SNP of Ask2 associated with the accumulation of lysine in the endosperm in CIMMYT germplasm, and 4) to develop high-throughput marker assays for these SNPs. The interaction study showed a preponderant effect of o2 on the accumulation of 11 amino acids (P ≤ 0.01). Ask2 appeared only to act with o2 to enhance marginally lysine, histidine and methionine levels in the double recessive homozygotes. Sequencing of amplicons at the o2 locus led to the identification of an SNP in exon 1 that discriminated all QPM (C) genotypes from non-QPM (T) genotypes. Validation of this SNP through KASP™ assays indicated that it was 92 % assertive in differentiating the o2 genotypes. In contrast, the frequency of the Ask2 SNP in CIMMYT QPM germplasm was low; however, an SSCP marker developed using this SNP detected five variants indicating that other unknown base changes may confer positive lysine-increasing responses. These markers could aid the marker-assisted selection of QPM cultivars

Revista de Vertebrados de la Estación Biológica de Doñana

Contribución al estudio de la bermejuela Rutilus arcasi, Steindachner, 1866 de la cuenca del Júcar (Osteichthyes: Cyprinidae)II. Edad y crecimientoSobre la taxonomía de Barbus comiza Steindachner, 1865 (Ostariophysi: Cyprinidae)Fenología de una comunidad de anfibios asociada a cursos fluviales temporales.Nueva especie para la ciencia de Anolis (Lacertilia: Iguanidae) de Cuba pertenecient eal complejo argillaceusSegregación ecológica en una comunidad de ofidios.El Aguila Imperial (Aquila adalberti): dispersión de los jóvenes, estructura de edades y mortalidaSobre diferencias individuales en la alimentación de Tyto albaInfluencia de las condiciones ambientales sobre la organización de la comunidad de aves invernantes en un bosque subalpino mediterráneoVariaciones en la agregación y distribución de la cabra montés (Capra pyrenaica Schinz,1838) detectadas con un muestreo de excrementosAlimentación del conejo (Oryctolagus cuniculus L. 1758) en Doñana. SO, EspañaSobre la distribución de Barbus meridionales Risso, 1826 (Ostariophysi: Cyprinidae) en la Península IbéricaSobre la distribución de Barbus meridionales Risso, 1826 (Ostariophysi: Cyprinidae) en la Península IbéricaNueva cita de Barbus microcephalus Almaça (Pisces, Cyprinidae) en España.Revisión taxonómica y distribución de Cobitis maroccana Pellegrin, 1929 (Osteichthyes, Cobitidae)Datos sobre una población de Lacerta viviparaSobre la presencia de Emys orbicularis en la provincia de León.Algunas observaciones sobre la captura de quirópteros por Falco subbuteo y Falco tinunculusNyctalus leisleri (Kuhk, 1818) (Mammalia: Chiroptera). Una nueva especie para las islas CanariaNuevos datos acerca de la distribución del topillo campesino Microtus arvalis, PALLAS 1778, en la Península IbéricaPeer reviewe

Surface indicators are correlated with soil multifunctionality in global drylands

Multiple ecosystem functions need to be considered simultaneously to manage and protect the several ecosystem services that are essential to people and their environments. Despite this, cost effective, tangible, relatively simple and globally relevant methodologies to monitor in situ soil multifunctionality, that is, the provision of multiple ecosystem functions by soils, have not been tested at the global scale. We combined correlation analysis and structural equation modelling to explore whether we could find easily measured, field-based indicators of soil multifunctionality (measured using functions linked to the cycling and storage of soil carbon, nitrogen and phosphorus). To do this, we gathered soil data from 120 dryland ecosystems from five continents. Two soil surface attributes measured in situ (litter incorporation and surface aggregate stability) were the most strongly associated with soil multifunctionality, even after accounting for geographic location and other drivers such as climate, woody cover, soil pH and soil electric conductivity. The positive relationships between surface stability and litter incorporation on soil multifunctionality were greater beneath the canopy of perennial vegetation than in adjacent, open areas devoid of vascular plants. The positive associations between surface aggregate stability and soil functions increased with increasing mean annual temperature. Synthesis and applications. Our findings demonstrate that a reduced suite of easily measured in situ soil surface attributes can be used as potential indicators of soil multifunctionality in drylands world-wide. These attributes, which relate to plant litter (origin, incorporation, cover), and surface stability, are relatively cheap and easy to assess with minimal training, allowing operators to sample many sites across widely varying climatic areas and soil types. The correlations of these variables are comparable to the influence of climate or soil, and would allow cost-effective monitoring of soil multifunctionality under changing land-use and environmental conditions. This would provide important information for evaluating the ecological impacts of land degradation, desertification and climate change in drylands world-wide.Fil: Eldridge, David J.. University of New South Wales; AustraliaFil: Delgado Baquerizo, Manuel. Universidad Rey Juan Carlos; EspañaFil: Quero, José L.. Universidad de Córdoba; EspañaFil: Ochoa, Victoria. Universidad Rey Juan Carlos; España. Universidad de Alicante; EspañaFil: Gozalo, Beatriz. Universidad Rey Juan Carlos; España. Universidad de Alicante; EspañaFil: García Palacios, Pablo. Universidad Rey Juan Carlos; EspañaFil: Escolar, Cristina. Universidad Rey Juan Carlos; EspañaFil: García Gómez, Miguel. Universidad Politécnica de Madrid; EspañaFil: Prina, Aníbal. Universidad Nacional de La Pampa; ArgentinaFil: Bowker, Mathew A.. Northern Arizona University; Estados UnidosFil: Bran, Donaldo Eduardo. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Patagonia Norte. Estación Experimental Agropecuaria San Carlos de Bariloche; ArgentinaFil: Castro, Ignacio. Universidad Experimental Simón Rodríguez; VenezuelaFil: Cea, Alex. Universidad de La Serena; ChileFil: Derak, Mchich. No especifíca;Fil: Espinosa, Carlos I.. Universidad Técnica Particular de Loja; EcuadorFil: Florentino, Adriana. Universidad Central de Venezuela; VenezuelaFil: Gaitán, Juan José. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación de Recursos Naturales. Instituto de Suelos; Argentina. Universidad Nacional de Luján. Departamento de Tecnología; ArgentinaFil: Gatica, Mario Gabriel. Universidad Nacional de San Juan. Facultad de Ciencias Exactas Físicas y Naturales. Departamento de Biología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan. Centro de Investigaciones de la Geosfera y Biosfera. Universidad Nacional de San Juan. Facultad de Ciencias Exactas Físicas y Naturales. Centro de Investigaciones de la Geosfera y Biosfera; ArgentinaFil: Gómez González, Susana. Universidad de Cádiz; EspañaFil: Ghiloufi, Wahida. Université de Sfax; TúnezFil: Gutierrez, Julio R.. Universidad de La Serena; ChileFil: Guzman, Elizabeth. Universidad Técnica Particular de Loja; EcuadorFil: Hernández, Rosa M.. Universidad Experimental Simón Rodríguez; VenezuelaFil: Hughes, Frederic M.. Universidade Estadual de Feira de Santana; BrasilFil: Muiño, Walter. Universidad Nacional de La Pampa; ArgentinaFil: Monerris, Jorge. No especifíca;Fil: Ospina, Abelardo. Universidad Central de Venezuela; VenezuelaFil: Ramírez, David A.. International Potato Centre; PerúFil: Ribas Fernandez, Yanina Antonia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan. Centro de Investigaciones de la Geosfera y Biosfera. Universidad Nacional de San Juan. Facultad de Ciencias Exactas Físicas y Naturales. Centro de Investigaciones de la Geosfera y Biosfera; ArgentinaFil: Romão, Roberto L.. Universidade Estadual de Feira de Santana; BrasilFil: Torres Díaz, Cristian. Universidad del Bio Bio; ChileFil: Koen, Terrance B.. No especifíca;Fil: Maestre, Fernando T.. Universidad Rey Juan Carlos; España. Universidad de Alicante; Españ

Synthesis of a square-planar rhodium alkylidene N-heterocyclic carbene complex and its reactivity toward alkenes

The first rhodium alkylidene square-planar complex stabilized by an N-heterocyclic carbene ligand, RhCl(-CHPh)(IPr)PPh3 (2; IPr = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-carbene), has been prepared by reaction of RhCl(IPr)(PPh3)2 (1) with phenyldiazomethane and its dynamic behavior in solution studied. Treatment of 2 with alkenes results in the formation of the ¿2-olefin complexes RhCl(¿2-CH2-CHR)(IPr)PPh3 (3, R = H; 4, R = Ph; 5, R = OEt) and new olefins arising from the coupling of the alkylidene with the alkenes, likely via a metallacyclobutane intermediate