Contribution of Yap 1 towards S. cervisiae adaptation to arsenic mediated oxidative stress

Post-PrintIn the budding yeast Saccharomyces cerevisiae arsenic detoxification involves the activation Yap8, a member of the Yap family of transcription factors, which in turn regulates ACR2 and ACR3, encoding an arsenate reductase and a plasma membrane arsenite efflux-protein, respectively. In addition, Yap1 is involved in the arsenic adaptation process through regulating the expression of the vacuolar-pump encoded by YCF1 and also contributing to the regulation of ACR genes. Here we show that Yap1 is also involved in the removal of ROS generated by arsenic compounds. Data on lipid peroxidation and intracellular oxidation indicate that deletion of YAP1 and YAP8 triggers cellular oxidation mediated by inorganic arsenic. In spite of the increased amounts of As(III) absorbed by the yap8 mutant, the enhanced transcriptional activation of the antioxidant genes such as GSH1, SOD1 and TRX2 may prevent protein oxidation. In contrast, the yap1 mutant exhibits high contents of protein carbonyl groups and the GSSG:GSH ratio is severely disturbed upon exposure to arsenic compounds in these cells. These results point to an additional level of Yap1 contribution to arsenic stress responses by preventing oxidative damage in cells exposed to these compounds. Transcriptional profiling revealed that genes of the functional categories related with sulphur and methionine metabolism and with the maintenance of the cell redox homeostasis are activated to mediate adaptation of the wild type strain to 2 mM arsenate treatmen

Partially premixed flame reactive flow characterization in a bluff body burner

Paper presented to the 10th International Conference on Heat Transfer, Fluid Mechanics and Thermodynamics, Florida, 14-16 July 2014.The present work aims the characterization of a natural gas/air partially premixed flame (PPF) reactive flow in a bluff body burner under laminar conditions in equivalence ratio of 2.1, 1.7 and 1.2. The laboratorial bluff body burner is composed of a central outflow for the premixed reactants and an annular air flow. The latter allows for the stabilization of the flame meanwhile it prevents external aerodynamic influence on the behavior of the flame. For the velocity field measurements, a 2-D Particle Image Velocimetry, PIV, optical diagnostic system is employed. The PIV system comprises of two Nd:YAG lasers with an output wavelength of 532 nm. Titanium dioxide particles, TiO2, are used as seeding particles in the premixed flow. The displacement of the seeding particles between two laser pulses with a known short time difference allows a planar velocity field determination. The stored images are processed using a software integrated with the system in order to obtain the medium velocity field. The software uses statistic data to obtain the correlation between two images acquired in an interval of time of an overlapped interrogation window. The major objective of this study is to examine the flame velocity field of laminar partially premixed natural gas and air flames in rich conditions. Three premixed flames under rich conditions have been studied in the present work with equivalence ratios of 2.1, 1.7 and 1.2 respectively. The study focused on: (1) analyze the instantaneous velocity flow field of the three partially premixed flames, (2) analyze the mean velocity flow field formed from the instantaneous flow fields and (3) analyze the velocity behavior along the center line of the flame.cf201

ST6Gal1 targets the ectodomain of ErbB2 in a site-specific manner and regulates gastric cancer cell sensitivity to trastuzumab

The clinical performance of the therapeutic monoclonal antibody trastuzumab in the treatment of ErbB2-positive unresectable gastric cancer (GC) is severely hampered by the emergence of molecular resistance. Trastuzumab's target epitope is localized within the extracellular domain of the oncogenic cell surface receptor tyrosine kinase (RTK) ErbB2, which is known to undergo extensive N-linked glycosylation. However, the site-specific glycan repertoire of ErbB2, as well as the detailed molecular mechanisms through which specific aberrant glycan signatures functionally impact the malignant features of ErbB2-addicted GC cells, including the acquisition of trastuzumab resistance, remain elusive. Here, we demonstrate that ErbB2 is modified with both alpha 2,6- and alpha 2,3-sialylated glycan structures in GC clinical specimens. In-depth mass spectrometry-based glycomic and glycoproteomic analysis of ErbB2's ectodomain disclosed a site-specific glycosylation profile in GC cells, in which the ST6Gal1 sialyltransferase specifically targets ErbB2 N-glycosylation sites occurring within the receptor's trastuzumab-binding domain. Abrogation of ST6Gal1 expression reshaped the cellular and ErbB2-specific glycomes, expanded the cellular half-life of the ErbB2 receptor, and sensitized ErbB2-dependent GC cells to trastuzumab-induced cytotoxicity through the stabilization of ErbB dimers at the cell membrane, and the decreased activation of both ErbB2 and EGFR RTKs. Overall, our data demonstrates that ST6Gal1-mediated aberrant alpha 2,6-sialylation actively tunes the resistance of ErbB2-driven GC cells to trastuzumab.Proteomic

Haematological and biochemical parameters in Churra-da-Terra-Quente ewes from the northeast of Portugal

Hematological and biochemical parameters, including plasma electrolytes and thyroid hormones, were determined in 73 clinically healthy Churra-da-Terra-Quente ewes, a typical breed from the northeast of Portugal. The hemogram values were: erythrocytes 9.8±1.51012/L; haemoglobin 118.1±19.1g/L; haematocrit 40.8±5.9%; leukocytes 5.7±1.8109/L; and platelets 544.3±177.2109/L. The thrombin time was 17.3±1.7 seconds. The values of biochemical parameters were: total protein 76.4±6.1g/L; glucose 2.87±0.60mmol/L; total cholesterol 1.65±0.33mmol/L; aspartate aminotransferase 155.9±49.2U/L; alanine aminotransferase 23.2±9.6U/L; γ-glutamyl transferase 48.0±18.7U/L; total alkaline phosphatase 121.6±76.1U/L; glutamate dehydrogenase 6.4±3.7U/L; urea 7.32±2.22mmol/L; creatinine 123.0±54.1μmol/L; total calcium 2.53±0.25mmol/L; phosphorus 2.10±0.46mmol/L; magnesium 1.01±0.09mmol/L; sodium 152.04±3.65mmol/L; potassium 4.7±0.4mmol/L; ionized calcium 1.32±0.07mmol/L; total thyroxine 111.75±42.29nmol/L; total triiodothyronine 1.01±0.28nmol/L; free T4 11.93±1.78pmol/L; free T3 4.22±1.33pmol/L; and thyroid-stimulating hormone 0.18±0.19μIU/mL. Although differences among the Churra-da-Terra-Quente breed and other breeds may occur, the hematological and biochemical parameters, plasma electrolytes, and thyroid hormones, for this indigenous breed, were generally situated within the reference intervals previously reported for sheep