Icebergs in the North Atlantic: Modelling circulation changes and glacio-marine deposition

In order to investigate meltwater events in the North Atlantic, a simple iceberg generation, drift, and melting routine was implemented in a high-resolution OGCM. Starting from the modelled last glacial state, every 25th day cylindrical model icebergs 300 meters high were released at 32 specific points along the coasts. Icebergs launched at the Barents Shelf margin spread a light meltwater lid over the Norwegian and Greenland Seas, shutting down the deep convection and the anti-clockwise circulation in this area. Due to the constraining ocean circulation, the icebergs produce a tongue of relatively cold and fresh water extending eastward from Hudson Strait that must develop at this location, regardless of iceberg origin. From the total amount of freshwater inferred by the icebergs, the thickness of the deposited IRD could be calculated in dependance of iceberg sediment concentration. In this way, typical extent and thickness of Heinrich layers could be reproduced, running the model for 250 years of steady state with constant iceberg meltwater inflow

The Atlantic Ocean at the last glacial maximum: 1. Objective mapping of the GLAMAP sea-surface conditions

Recent efforts of the German paleoceanographic community have resulted in a unique data set of reconstructed sea-surface temperature for the Atlantic Ocean during the Last Glacial Maximum, plus estimates for the extents of glacial sea ice. Unlike prior attempts, the contributing research groups based their data on a common definition of the Last Glacial Maximum chronozone and used the same modern reference data for calibrating the different transfer techniques. Furthermore, the number of processed sediment cores was vastly increased. Thus the new data is a significant advance not only with respect to quality, but also to quantity. We integrate these new data and provide monthly data sets of global sea-surface temperature and ice cover, objectively interpolated onto a regular 1°x1° grid, suitable for forcing or validating numerical ocean and atmosphere models. This set is compared to an existing subjective interpolation of the same base data, in part by employing an ocean circulation model. For the latter purpose, we reconstruct sea surface salinity from the new temperature data and the available oxygen isotope measurements

Interactivity Mitigates the Impact of Working Memory Depletion on Mental Arithmetic Performance

Doing long sums in the absence of complementary actions or artefacts is a multi-step procedure that quickly taxes working memory; congesting the phonological loop further handicaps performance. In the experiment reported here, participants completed long sums either with hands down?the low interactivity condition?or by moving numbered tokens?the high interactivity condition?while they repeated ?the? continuously, loading the phonological loop, or not. As expected, interactivity and articulatory suppression substantially affected performance; critically, the effect of articulatory suppression was stronger in the low than in the high interactivity condition. In addition, independent measure of mathematics anxiety predicted the impact of articulatory suppression on performance only in the low (not high) interactivity condition. These findings suggest that interactivity augmented overall or systemic working memory resources and diminished the effect of mathematics anxiety, underscoring the importance of characterizing the properties of the system as it is configured by the dynamic agent-environment coupling

Downregulation of SFRP5 expression and its inverse correlation with those of MMP-7 and MT1-MMP in gastric cancer

<p>Abstract</p> <p>Background</p> <p>As negative regulators in Wnt signaling, Secreted Frizzled-Related Proteins (SFRPs) are downregulated in a series of human cancers; and specifically, some matrix metalloproteinases (MMPs), including MMP-2, MMP-7, MMP-9 and MT1-MMP, are frequently overexpressed in gastric cancer. The aim of this study is to determine the expression status of SFRP5 in gastric cancer and explore the correlation between both the expression of SFRP5 and that of these MMPs in this cancer.</p> <p>Methods</p> <p>Expression of SFRP5, MMP-2, MMP-7, MMP-9 and MT1-MMP was determined by real-time PCR, RT-PCR or Western blotting. The methylation status of <it>SFRP5 </it>was detected by Methylation-specific PCR (MSP). Cell lines with <it>SFRP5 </it>methylation were demethylated by a DNA methyltransferase inhibitor 5-Aza-2'-deoxycytidine (DAC). KatoIII cells were transfected with pcDNA3.1 <it>SFRP5 </it>vector to strengthen SFRP5 expression. To abrogate SFRP5 expression in MKN1 cells, <it>SFRP5 </it>RNAi plamid was used to transfect them.</p> <p>Results</p> <p>SFRP5 expression was remarkably downregulated in 24 of 32 primary gastric cancer specimens, and even was not detectable in 5 of 8 gastric cancer cell lines. MMP-7 and MT1-MMP mRNA showed a stronger expression in these 24 specimens compared to the other 8 specimens. They also showed higher levels in gastric cancer cell lines AGS and NCI-N87 which had no SFRP5 expression, compared to MKN1 with strong SFRP5 expression. However, they were significantly downregulated, with SFRP5 expression restored in AGS and NCI-N87; and were considerably upregulated with it abrogated in MKN1.</p> <p>Conclusion</p> <p>The results indicate there are frequent occurrences of downregualtion of SFRP5 expression in gastric cancer, primarily due to <it>SFRP5 </it>methylation. It seems to be responsible for the upregulation of MMP-7 expression and MT1-MMP expression on the ground that they are inversely correlated with SFRP5 expression.</p

Down-regulation of frizzled-7 expression decreases survival, invasion and metastatic capabilities of colon cancer cells

BackgroundThe canonical Wnt signalling pathway is activated in most sporadic colorectal cancers (CRCs). We previously reported that FZD7 functions as a receptor for the canonical Wnt signalling pathway in colon cancer cells.Methods and resultsIn this study, we examined the function of FZD7 in survival, invasion and metastatic capabilities of colon cancer cells. FZD7_siRNA transfection decreased cell viability of HT-29 and HCT-116 colon cancer cells. Expression of c-Jun, phosphorylation of JNK and c-Jun, and activation of RhoA were suppressed after FZD7_siRNA transfection into HCT-116 cells. In vitro invasion activity and Wnt target gene expression were also reduced in HCT-116 cells transfected with FZD7_siRNA. Liver metastasis of stable FZD7_siRNA HCT-116 cell transfectants in scid mice was decreased to 40-50% compared to controls. The mRNA levels of FZD7 in 135 primary CRC tissues were examined by real-time PCR. FZD7 mRNA levels were significantly higher in stage II, III or IV tumours than in non-tumour tissues (P&lt;0.005), and overall survival was shorter in those patients with higher FZD7 expression (P&lt;0.001).ConclusionThese data suggest that FZD7 may be involved in enhancement of survival, invasion and metastatic capabilities of colon cancer cells through non-canonical Wnt signalling pathways as well as the canonical pathway

Expression analysis of E-cadherin, Slug and GSK3β in invasive ductal carcinoma of breast

<p>Abstract</p> <p>Background</p> <p>Cancer progression is linked to a partially dedifferentiated epithelial cell phenotype. The signaling pathways Wnt, Hedgehog, TGF-β and Notch have been implicated in experimental and developmental epithelial mesenchymal transition (EMT). Recent findings from our laboratory confirm that active Wnt/β-catenin signaling is critically involved in invasive ductal carcinomas (IDCs) of breast.</p> <p>Methods</p> <p>In the current study, we analyzed the expression patterns and relationships between the key Wnt/β-catenin signaling components- E-cadherin, Slug and GSK3β in IDCs of breast.</p> <p>Results</p> <p>Of the 98 IDCs analyzed, 53 (54%) showed loss/or reduced membranous staining of E-cadherin in tumor cells. Nuclear accumulation of Slug was observed in 33 (34%) IDCs examined. Loss or reduced level of cytoplasmic GSK3β expression was observed in 52/98 (53%) cases; while 34/98 (35%) tumors showed nuclear accumulation of GSK3β. Statistical analysis revealed associations of nuclear Slug expression with loss of membranous E-cadherin (p = 0.001); nuclear β-catenin (p = 0.001), and cytoplasmic β-catenin (p = 0.005), suggesting Slug mediated E-cadherin suppression via the activation of Wnt/β-catenin signaling pathway in IDCs. Our study also demonstrated significant correlation between GSK3β nuclear localization and tumor grade (p = 0.02), suggesting its association with tumor progression.</p> <p>Conclusion</p> <p>The present study for the first time provided the clinical evidence in support of Wnt/β-catenin signaling upregulation in IDCs and key components of this pathway - E-cadherin, Slug and GSK3β with β-catenin in implementing EMT in these cells.</p

Height and timing of growth spurt during puberty in young people living with vertically acquired HIV in Europe and Thailand.

OBJECTIVE: The aim of this study was to describe growth during puberty in young people with vertically acquired HIV. DESIGN: Pooled data from 12 paediatric HIV cohorts in Europe and Thailand. METHODS: One thousand and ninety-four children initiating a nonnucleoside reverse transcriptase inhibitor or boosted protease inhibitor based regimen aged 1-10 years were included. Super Imposition by Translation And Rotation (SITAR) models described growth from age 8 years using three parameters (average height, timing and shape of the growth spurt), dependent on age and height-for-age z-score (HAZ) (WHO references) at antiretroviral therapy (ART) initiation. Multivariate regression explored characteristics associated with these three parameters. RESULTS: At ART initiation, median age and HAZ was 6.4 [interquartile range (IQR): 2.8, 9.0] years and -1.2 (IQR: -2.3 to -0.2), respectively. Median follow-up was 9.1 (IQR: 6.9, 11.4) years. In girls, older age and lower HAZ at ART initiation were independently associated with a growth spurt which occurred 0.41 (95% confidence interval 0.20-0.62) years later in children starting ART age 6 to 10 years compared with 1 to 2 years and 1.50 (1.21-1.78) years later in those starting with HAZ less than -3 compared with HAZ at least -1. Later growth spurts in girls resulted in continued height growth into later adolescence. In boys starting ART with HAZ less than -1, growth spurts were later in children starting ART in the oldest age group, but for HAZ at least -1, there was no association with age. Girls and boys who initiated ART with HAZ at least -1 maintained a similar height to the WHO reference mean. CONCLUSION: Stunting at ART initiation was associated with later growth spurts in girls. Children with HAZ at least -1 at ART initiation grew in height at the level expected in HIV negative children of a comparable age