Local Difference Measures between Complex Networks for Dynamical System Model Evaluation

Acknowledgments We thank Reik V. Donner for inspiring suggestions that initialized the work presented herein. Jan H. Feldhoff is credited for providing us with the STARS simulation data and for his contributions to fruitful discussions. Comments by the anonymous reviewers are gratefully acknowledged as they led to substantial improvements of the manuscript.Peer reviewedPublisher PD

ZD6474 reverses multidrug resistance by directly inhibiting the function of P-glycoprotein

P-glycoprotein (P-gp) pumps multiple types of drugs out of the cell, using energy generated from ATP, and confers multidrug resistance (MDR) on cancer cells. ZD6474 is an orally active, selective inhibitor of the vascular endothelial growth factor receptor, epidermal growth factor receptor, and rearranged during transfection tyrosine kinases. This study was designed to examine whether ZD6474 reverses P-gp-mediated MDR in cancer cells. Here, we show that clinically achievable levels of ZD6474 reverse P-gp-mediated MDR of the P-gp-overexpressing cell lines derived from breast cancer, MCF-7/adriamycin (ADR), and human oral epidermoid carcinoma, KBV200 to ADR, docetaxel, and vinorelbine. This ability to reverse the P-gp-mediated resistance is comparable to that of another frequently used reversal agent known as verapamil. ZD6474 itself moderately inhibits the proliferation of both MCF-7 and MCF-7/ADR cells with almost equal activity, but its inhibitory effect is not altered by co-incubation with verapamil, suggesting that ZD6474 may not be a substrate of P-gp. In addition, ZD6474 increases the intracellular accumulation of the P-gp substrate, rhodamine-123, and ADR, by enhancing the uptake and/or decreasing the efflux of these compounds in resistant cells. Further studies show that ZD6474 stimulates ATPase activity in a dose-dependent manner, which is required for the proper function of P-gp. In contrast, ZD6474 does not inhibit the expression level of P-gp. Our results suggest that ZD6474 is capable of reversing MDR in cancer cells by directly inhibiting the function of P-gp, a finding that may have clinical implications for ZD6474

PGRMC1 phosphorylation affects cell shape, motility, glycolysis, mitochondrial form and function, and tumor growth.

BackgroundProgesterone Receptor Membrane Component 1 (PGRMC1) is expressed in many cancer cells, where it is associated with detrimental patient outcomes. It contains phosphorylated tyrosines which evolutionarily preceded deuterostome gastrulation and tissue differentiation mechanisms.ResultsWe demonstrate that manipulating PGRMC1 phosphorylation status in MIA PaCa-2 (MP) cells imposes broad pleiotropic effects. Relative to parental cells over-expressing hemagglutinin-tagged wild-type (WT) PGRMC1-HA, cells expressing a PGRMC1-HA-S57A/S181A double mutant (DM) exhibited reduced levels of proteins involved in energy metabolism and mitochondrial function, and altered glucose metabolism suggesting modulation of the Warburg effect. This was associated with increased PI3K/AKT activity, altered cell shape, actin cytoskeleton, motility, and mitochondrial properties. An S57A/Y180F/S181A triple mutant (TM) indicated the involvement of Y180 in PI3K/AKT activation. Mutation of Y180F strongly attenuated subcutaneous xenograft tumor growth in NOD-SCID gamma mice. Elsewhere we demonstrate altered metabolism, mutation incidence, and epigenetic status in these cells.ConclusionsAltogether, these results indicate that mutational manipulation of PGRMC1 phosphorylation status exerts broad pleiotropic effects relevant to cancer and other cell biology

Novel approach to analysing large data sets of personal sun exposure measurements

Personal sun exposure measurements provide important information to guide the development of sun awareness and disease prevention campaigns. We assess the scaling properties of personal ultraviolet radiation (pUVR) sun exposure measurements using the wavelet transform (WT) spectral analysis to process long-range, high-frequency personal recordings collected by electronic UVR dosimeters designed to measure erythemal UVR exposure. We analysed the sun exposure recordings of school children, farmers, marathon runners and outdoor workers in South Africa, and construction workers and work site supervisors in New Zealand. We found scaling behaviour in all the analysed pUVR data sets. We found that the observed scaling changes from uncorrelated to long-range correlated with increasing duration of sun exposure. Peaks in the WT spectra that we found suggest the existence of characteristic times in sun exposure behaviour that were to some extent universal across our data set. Our study also showed that WT measures enable group classification, as well as distinction between individual UVR exposures, otherwise unattainable by conventional statistical methods

Waist circumference, abdominal obesity, and depression among overweight and obese U.S. adults: national health and nutrition examination survey 2005-2006

<p>Abstract</p> <p>Background</p> <p>Obesity is associated with an increased risk of mental illness; however, evidence linking body mass index (BMI)-a measure of overall obesity, to mental illness is inconsistent. The objective of this study was to examine the association of depressive symptoms with waist circumference or abdominal obesity among overweight and obese U.S. adults.</p> <p>Methods</p> <p>A cross-sectional, nationally representative sample from the 2005-2006 National Health and Nutrition Examination Survey was used. We analyzed the data from 2,439 U.S. adults (1,325 men and 1,114 nonpregnant women) aged ≥ 20 years who were either overweight or obese with BMI of ≥ 25.0 kg/m². Abdominal obesity was defined as waist circumference of > 102 cm for men and > 88 cm for women. Depressive symptoms (defined as having major depressive symptoms or moderate-to-severe depressive symptoms) were assessed by the Patient Health Questionnaire-9 diagnostic algorithm. The prevalence and the odds ratios (ORs) with 95% confidence intervals (CIs) for having major depressive symptoms and moderate-to-severe depressive symptoms were estimated using logistic regression analysis.</p> <p>Results</p> <p>After multivariate adjustment for demographics and lifestyle factors, waist circumference was significantly associated with both major depressive symptoms (OR: 1.03, 95% CI: 1.01-1.05) and moderate-to-severe depressive symptoms (OR: 1.02, 95% CI: 1.01-1.04), and adults with abdominal obesity were significantly more likely to have major depressive symptoms (OR: 2.18, 95% CI: 1.35-3.59) or have moderate-to-severe depressive symptoms (OR: 2.56, 95% CI: 1.34-4.90) than those without. These relationships persisted after further adjusting for coexistence of multiple chronic conditions and persisted in participants who were overweight (BMI: 25.0-< 30.0 kg/m²) when stratified analyses were conducted by BMI status.</p> <p>Conclusion</p> <p>Among overweight and obese U.S. adults, waist circumference or abdominal obesity was significantly associated with increased likelihoods of having major depressive symptoms or moderate-to-severe depressive symptoms. Thus, mental health status should be monitored and evaluated in adults with abdominal obesity, particularly in those who are overweight.</p

Sucrose in the concentrated solution or the supercooled “state” : a review of caramelisation reactions and physical behaviour

Sucrose is probably one of the most studied molecules by food scientists, since it plays an important role as an ingredient or preserving agent in many formulations and technological processes. When sucrose is present in a product with a concentration near or greater than the saturation point—i.e. in the supercooled state—it possesses high potentialities for the food industry in areas as different as pastry industry, dairy and frozen desserts or films and coatings production. This paper presents a review on critical issues and research on highly concentrated sucrose solutions—mainly, on sucrose thermal degradation and relaxation behaviour in such solutions. The reviewed works allow identifying several issues with great potential for contributing to significant advances in Food Science and Technology.Authors are grateful for the valuable discussions with Teresa S. Brandao and Rosiane Lopes da Cunha during this research. Author M. A. C. Quintas acknowledges the financial support of her research by FCT grant SFRH/BPD/41715/2007

Inferring causation from time series in Earth system sciences

The heart of the scientific enterprise is a rational effort to understand the causes behind the phenomena we observe. In large-scale complex dynamical systems such as the Earth system, real experiments are rarely feasible. However, a rapidly increasing amount of observational and simulated data opens up the use of novel data-driven causal methods beyond the commonly adopted correlation techniques. Here, we give an overview of causal inference frameworks and identify promising generic application cases common in Earth system sciences and beyond. We discuss challenges and initiate the benchmark platform causeme.net to close the gap between method users and developers