Relationships between CYP2D6 phenotype, breast cancer and hot flushes in women at high risk of breast cancer receiving prophylactic tamoxifen: results from the IBIS-I trial

Licensed under a Creative Commons Attribution Non-Commercial Share Alike Licens

Combined and single effects of pesticide carbaryl and toxic Microcystis aeruginosa on the life history of Daphnia pulicaria

The combined influence of a pesticide (carbaryl) and a cyanotoxin (microcystin LR) on the life history of Daphnia pulicaria was investigated. At the beginning of the experiments animals were pulse exposed to carbaryl for 24 h and microcystins were delivered bound in Microcystis’ cells at different, sub-lethal concentrations (chronic exposure). In order to determine the actual carbaryl concentrations in the water LC–MS/MS was used. For analyses of the cyanotoxin concentration in Daphnia’s body enzyme-linked immunosorbent assay (ELISA) was used. Individual daphnids were cultured in a flow-through system under constant light (16 h of light: 8 h of dark), temperature (20°C), and food conditions (Scenedesmus obliquus, 1 mg of C l−1). The results showed that in the treatments with carbaryl egg numbers per female did not differ significantly from controls, but the mortality of newborns increased significantly. Increasing microcystin concentrations significantly delayed maturation, reduced size at first reproduction, number of eggs, and newborns. The interaction between carbaryl and Microcystis was highly significant. Animals matured later and at a smaller size than in controls. The number of eggs per female was reduced as well. Moreover, combined stressors caused frequent premature delivery of offspring with body deformations such as dented carapax or an undeveloped heart. This effect is concluded to be synergistic and could not be predicted from the effects of the single stressors.

Mineral analysis of complete dog and cat foods in the UK and compliance with European guidelines

Mineral content of complete pet food is regulated to ensure health of the companion animal population. Analysis of adherence to these regulatory guidelines has not been conducted. Here, mineral composition of complete wet (n = 97) and dry (n = 80) canine and feline pet food sold in the UK was measured to assess compliance with EU guidelines. A majority of foods complied with ≥8 of 11 guidelines (99% and 83% for dry and wet food, respectively), but many failed to provide nutritional minimum (e.g. Cu, 20% of wet food) or exceeded nutritional maximum (e.g. Se, 76% of wet food). Only 6% (6/97) of wet and 38% (30/80) of dry food were fully compliant. Some foods (20–30% of all analysed) had mineral imbalance, such as not having the recommended ratio of Ca:P (between 1:1 to 2:1). Foods with high fish content had high levels of undesirable metal elements such as arsenic. This study highlights broad non-compliance of a range of popular pet foods sold in the UK with EU guidelines (94% and 61% of wet and dry foods, respectively). If fed exclusively and over an extended period, a number of these pet foods could impact the general health of companion animals

Experimental testing of reciprocal effects of nutrition and parasitism in wild black capuchin monkeys

Nutritional stress may predispose individuals to infection, which in turn can have further detrimental effects on physical condition, thus creating an opportunity for reciprocal effects between nutrition and parasitism. Little experimental investigation has been conducted on this "vicious circle" hypothesis in wild animals, especially under natural conditions. We evaluated the reciprocal effects of nutritional status and parasitism using an experimental approach in two groups of wild black capuchin monkeys (Sapajus nigritus). Across two consecutive winters, we collected faecal samples from identified capuchins to determine presence and load of gastrointestinal helminthes, and measured individual body mass as a proxy of physical condition. Food availability was manipulated by provisioning monkeys with bananas, and parasite burdens by applying anti-parasitic drugs to selected individuals. We found no effect of anti-parasitic drugs on physical condition, but parasite loads decreased in response to high levels of food availability. Our results represent the first experimental evidence that the nutritional status may drive parasite dynamics in a primate.Fil: Agostini, Ilaria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Biología Subtropical. Universidad Nacional de Misiones. Instituto de Biología Subtropical; Argentina. Centro de Investigaciones del Bosque Atlántico; ArgentinaFil: Vanderhoeven, Ezequiel Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste; Argentina. Ministerio de Salud. Instituto Nacional de Medicina Tropical; Argentina. Centro de Investigaciones del Bosque Atlántico; ArgentinaFil: Di Bitetti, Mario Santiago. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Biología Subtropical. Universidad Nacional de Misiones. Instituto de Biología Subtropical; Argentina. Centro de Investigaciones del Bosque Atlántico; ArgentinaFil: Beldomenico, Pablo Martín. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - CONICET - Santa Fe. Instituto de Ciencias Veterinarias del Litoral; Argentina. Laboratorio de Ecología de Enfermedades; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Ciencias Veterinarias del Litoral. Universidad Nacional del Litoral. Facultad de Ciencias Veterinarias. Instituto de Ciencias Veterinarias del Litoral; Argentin

Summer warming explains widespread but not uniform greening in the Arctic tundra biome

Arctic warming can influence tundra ecosystem function with consequences for climate feedbacks, wildlife and human communities. Yet ecological change across the Arctic tundra biome remains poorly quantified due to field measurement limitations and reliance on coarse-resolution satellite data. Here, we assess decadal changes in Arctic tundra greenness using time series from the 30 m resolution Landsat satellites. From 1985 to 2016 tundra greenness increased (greening) at ~37.3% of sampling sites and decreased (browning) at ~4.7% of sampling sites. Greening occurred most often at warm sampling sites with increased summer air temperature, soil temperature, and soil moisture, while browning occurred most often at cold sampling sites that cooled and dried. Tundra greenness was positively correlated with graminoid, shrub, and ecosystem productivity measured at field sites. Our results support the hypothesis that summer warming stimulated plant productivity across much, but not all, of the Arctic tundra biome during recent decades

Role of LKB1 in lung cancer development

Three phenotypically related genetic syndromes and their lesions (LKB1, PTEN, and TSC1/2) are identified as frequently altered in lung cancer. LKB1, a kinase inactivated in 30% of lung cancers, is discussed in this review. Loss of LKB1 regulation often coincident with KRAS activation allows for unchecked growth and the metabolic capacity to accommodate the proliferation

Airway branching morphogenesis in three dimensional culture

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldBACKGROUND: Lungs develop from the fetal digestive tract where epithelium invades the vascular rich stroma in a process called branching morphogenesis. In organogenesis, endothelial cells have been shown to be important for morphogenesis and the maintenance of organ structure. The aim of this study was to recapitulate human lung morphogenesis in vitro by establishing a three dimensional (3D) co-culture model where lung epithelial cells were cultured in endothelial-rich stroma. METHODS: We used a human bronchial epithelial cell line (VA10) recently developed in our laboratory. This cell line cell line maintains a predominant basal cell phenotype, expressing p63 and other basal markers such as cytokeratin-5 and -14. Here, we cultured VA10 with human umbilical vein endothelial cells (HUVECs), to mimic the close interaction between these cell types during lung development. Morphogenesis and differentiation was monitored by phase contrast microscopy, immunostainings and confocal imaging. RESULTS: We found that in co-culture with endothelial cells, the VA10 cells generated bronchioalveolar like structures, suggesting that lung epithelial branching is facilitated by the presence of endothelial cells. The VA10 derived epithelial structures display various complex patterns of branching and show partial alveolar type-II differentiation with pro-Surfactant-C expression. The epithelial origin of the branching VA10 colonies was confirmed by immunostaining. These bronchioalveolar-like structures were polarized with respect to integrin expression at the cell-matrix interface. The endothelial-induced branching was mediated by soluble factors. Furthermore, fibroblast growth factor receptor-2 (FGFR-2) and sprouty-2 were expressed at the growing tips of the branching structures and the branching was inhibited by the FGFR-small molecule inhibitor SU5402. DISCUSSION: In this study we show that a human lung epithelial cell line can be induced by endothelial cells to form branching bronchioalveolar-like structures in 3-D culture. This novel model of human airway morphogenesis can be used to study critical events in human lung development and suggests a supportive role for the endothelium in promoting branching of airway epithelium

Structural Stability of Human Protein Tyrosine Phosphatase ρ Catalytic Domain: Effect of Point Mutations

Protein tyrosine phosphatase ρ (PTPρ) belongs to the classical receptor type IIB family of protein tyrosine phosphatase, the most frequently mutated tyrosine phosphatase in human cancer. There are evidences to suggest that PTPρ may act as a tumor suppressor gene and dysregulation of Tyr phosphorylation can be observed in diverse diseases, such as diabetes, immune deficiencies and cancer. PTPρ variants in the catalytic domain have been identified in cancer tissues. These natural variants are nonsynonymous single nucleotide polymorphisms, variations of a single nucleotide occurring in the coding region and leading to amino acid substitutions. In this study we investigated the effect of amino acid substitution on the structural stability and on the activity of the membrane-proximal catalytic domain of PTPρ. We expressed and purified as soluble recombinant proteins some of the mutants of the membrane-proximal catalytic domain of PTPρ identified in colorectal cancer and in the single nucleotide polymorphisms database. The mutants show a decreased thermal and thermodynamic stability and decreased activation energy relative to phosphatase activity, when compared to wild- type. All the variants show three-state equilibrium unfolding transitions similar to that of the wild- type, with the accumulation of a folding intermediate populated at ∼4.0 M urea