All about the marine/sea ice diatom Nitzschia lecointei

Generally, in terms of growth N. lecointei seems quite tolerant to changes in pH and pCO2, probably due to the fact that this species grows in an environment with large seasonal variations in the carbonate system. However, increased pCO2 resulted in physiological changes that may have important ecological consequences, such as cellular stoichiometry. For instance, we observed changes in carbon metabolism, and fatty acid content and composition, that did not affect the growth rate. When the experimental period was increased (194 days, ca. 60 asexual generations), we observed a small reduction in growth at 960 µatm pCO2 after 147 days. Carbon metabolism was significantly affected, resulting in higher cellular release of dissolved organic carbon. When studying the synergism between temperature (−1.8 and 2.5°C) and pCO2 (390 and 960 μatm), synergism was detected in growth rate and acyl lipid fatty acid content. Carbon enrichment only promoted (3 %) growth rate closer to the optimal growth, but not at the control temperature (−1.8°C). Optimal growth rate was observed around 5°C in a separate experiment. The total content of fatty acids was reduced at elevated pCO2, but only at the control temperature. PUFAs were reduced at high pCO2. When combining increased temperature and different salinity conditions, the growth rate was higher at 3°C than at -1.8°C. Salinity 10 clearly limited growth rate and the highest growth rates were found at salinity 20 and 35. In another experiment, high and low temperature together with treatments simulating ice formation and melting conditions were studied. Here, the highest levels of oxidative stress were found in low temperature and ice melting treatments, respectively. With respect to 9 weeks in the dark, cell numbers were higher at -1.5°C compared to 3°C, but when retrieved to light conditions, after one week higher cell numbers were observed at 3°C versus -1.5°C. Furthermore, cell numbers were lower when acetateUniversidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Overlap in serum metabolic profiles between non-related diseases: Implications for LC-MS metabolomics biomarker discovery

AbstractUntargeted metabolic profiling has generated large activity in the field of clinical biomarker discovery. Yet, no clinically approved metabolite biomarkers have emerged with failure in validation phases often being a reason. To investigate why, we have applied untargeted metabolic profiling in a retrospective cohort of serum samples representing non-related diseases. Age and gender matched samples from patients diagnosed with pneumonia, congestive heart failure, lymphoma and healthy controls were subject to comprehensive metabolic profiling using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). The metabolic profile of each diagnosis was compared to the healthy control group and significant metabolites were filtered out using t-test with FDR correction. Metabolites found to be significant between each disease and healthy controls were compared and analyzed for overlap. Results show that despite differences in etiology and clinical disease presentation, the fraction of metabolites with an overlap between two or more diseases was 61%. A majority of these metabolites can be associated with immune responses thus representing non-disease specific events. We show that metabolic serum profiles from patients representing non-related diseases display very similar metabolic differences when compared to healthy controls. Many of the metabolites discovered as disease specific in this study have further been associated with other diseases in the literature. Based on our findings we suggest non-related disease controls in metabolomics biomarker discovery studies to increase the chances of a successful validation and future clinical applications

Cystatin C Is Downregulated in Prostate Cancer and Modulates Invasion of Prostate Cancer Cells via MAPK/Erk and Androgen Receptor Pathways

Cystatin C is believed to prevent tumor progression by inhibiting the activities of a family of lysosomal cysteine proteases. However, little is known about the precise mechanism of cystatin C function in prostate cancer. In the present study, we examined the expression of cystatin C and its association with matrix metalloproteinases 2 (MMP2) and androgen receptor (AR) in a tissue microarray comparing benign and malignant specimens from 448 patients who underwent radical prostatectomy for localized prostate cancer. Cystatin C expression was significantly lower in cancer specimens than in benign tissues (p<0.001) and there was a statistically significant inverse correlation between expression of cystatin C and MMP2 (rs2 = −0.056, p = 0.05). There was a clear trend that patients with decreased level of cystatin C had lower overall survival. Targeted inhibition of cystatin C using specific siRNA resulted in an increased invasiveness of PC3 cells, whereas induction of cystatin C overexpression greatly reduced invasion rate of PC3 in vitro. The effect of cystatin C on modulating the PC3 cell invasion was provoked by Erk2 inhibitor that specifically inhibited MAPK/Erk2 activity. This suggests that cystatin C may mediate tumor cell invasion by modulating the activity of MAPK/Erk cascades. Consistent with our immunohistochemical findings that patients with low expression of cystatin C and high expression of androgen receptor (AR) tend to have worse overall survival than patients with high expression of cystatin C and high AR expression, induced overexpression of AR in PC3 cells expressing cystatin C siRNA greatly enhanced the invasiveness of PC3 cells. This suggests that there may be a crosstalk between cystatin C and AR-mediated pathways. Our study uncovers a novel role for cystatin C and its associated cellular pathways in prostate cancer invasion and metastasis

Zircon U-Pb, Hf and O isotope constraints on growth versus reworking of continental crust in the subsurface Grenville orogen, Ohio, USA

Combined U-Pb, O and Hf isotope data in zircon allows discrimination between juvenile and reworked crust, and is therefore a useful tool for understanding formation and evolution of the continental crust. The crustal evolution of basement rocks in central North America (Laurentia) is poorly constrained, as it is almost entirely overlain by Palaeozoic cover. In order to improve our understanding of the evolution of this region we present U-Pb, O and Hf isotope data from zircon in drill-core samples from the subsurface basement of Ohio. The Hf isotope data suggests juvenile crust formation at similar to 1650 Ma followed by continued reworking of a single reservoir. This similar to 1650 Ma reservoir was tapped at similar to 1450 Ma during the formation of the Granite-Rhyolite Province and subsequently reworked again during the Grenvillian orogeny. The similar to 1650 Ma crust formation model age for the suite of samples along with the presence of similar to 1650 Ma magmatic rocks suggests an eastward extension of the Mazatzal Province (or Mazatzal-like crust) and makes it a possible protolith to the subsurface basement of Ohio and surrounding Mesoproterozoic (i.e. Grenville-age) rocks. The eastward extension of this similar to 1650 Ma crustal reservoir into Ohio requires a revision of the crustal boundary defined by Nd isotopic data to be located further east, now overlapping with the Grenville front magnetic lineament in Ohio. In fact, the easternmost sample in this study is derived from a more depleted reservoir. This limits the extent of >1.5 Ga basement in subsurface Ohio and constrains the location of the crustal boundary. Further, syn-orogenic magmatism at similar to 1050 Ma suggests a potential extrapolation of the Interior Magmatic Belt into Ohio. Oxygen isotopic data in zircon suggests that during Grenvillian metamorphism, zircon recrystallisation occurred in the presence of heavy delta O-18 fluids resulting in zircon with elevated delta O-18 values. (C) 2015 Elsevier B.V. All rights reserved