β-Catenin–induced melanoma growth requires the downstream target Microphthalmia-associated transcription factor

The transcription factor Microphthalmia-associated transcription factor (MITF) is a lineage-determination factor, which modulates melanocyte differentiation and pigmentation. MITF was recently shown to reside downstream of the canonical Wnt pathway during melanocyte differentiation from pluripotent neural crest cells in zebrafish as well as in mammalian melanocyte lineage cells. Although expression of many melanocytic/pigmentation markers is lost in human melanoma, MITF expression remains intact, even in unpigmented tumors, suggesting a role for MITF beyond its role in differentiation. A significant fraction of primary human melanomas exhibit deregulation (via aberrant nuclear accumulation) of β-catenin, leading us to examine its role in melanoma growth and survival. Here, we show that β-catenin is a potent mediator of growth for melanoma cells in a manner dependent on its downstream target MITF. Moreover, suppression of melanoma clonogenic growth by disruption of β-catenin–T-cell transcription factor/LEF is rescued by constitutive MITF. This rescue occurs largely through a prosurvival mechanism. Thus, β-catenin regulation of MITF expression represents a tissue-restricted pathway that significantly influences the growth and survival behavior of this notoriously treatment-resistant neoplasm

Sex-Dependent Influences of Obesity on Cerebral White Matter Investigated by Diffusion-Tensor Imaging

Several studies have shown that obesity is associated with changes in human brain function and structure. Since women are more susceptible to obesity than men, it seems plausible that neural correlates may also be different. However, this has not been demonstrated so far. To address this issue, we systematically investigated the brain's white matter (WM) structure in 23 lean to obese women (mean age 25.5 y, std 5.1 y; mean body mass index (BMI) 29.5 kg/m(2), std 7.3 kg/m(2)) and 26 lean to obese men (mean age 27.1 y, std 5.0 y; mean BMI 28.8 kg/m(2), std 6.8 kg/m(2)) with diffusion-weighted magnetic resonance imaging (MRI). There was no significant age (p > 0.2) or BMI (p > 0.7) difference between female and male participants. Using tract-based spatial statistics, we correlated several diffusion parameters including the apparent diffusion coefficient, fractional anisotropy (FA), as well as axial (lambda(parallel to)) and radial diffusivity (lambda(perpendicular to)) with BMI and serum leptin levels. In female and male subjects, the putative axon marker lambda(parallel to) was consistently reduced throughout the corpus callosum, particularly in the splenium (r = -0.62, p < 0.005). This suggests that obesity may be associated with axonal degeneration. Only in women, the putative myelin marker lambda(perpendicular to) significantly increased with increasing BMI (r = 0.57, p < 0.005) and serum leptin levels (r = 0.62, p < 0.005) predominantly in the genu of the corpus callosum, suggesting additional myelin degeneration. Comparable structural changes were reported for the aging brain, which may point to accelerated aging of WM structure in obese subjects. In conclusion, we demonstrate structural WM changes related to an elevated body weight, but with differences between men and women. Future studies on obesity-related functional and structural brain changes should therefore account for sex-related differences

Strategies towards enabling lithium metal in batteries: interphases and electrodes

Despite the continuous increase in capacity, lithium-ion intercalation batteries are approaching their performance limits. As a result, research is intensifying on next-generation battery technologies. The use of a lithium metal anode promises the highest theoretical energy density and enables use of lithium-free or novel high-energy cathodes. However, the lithium metal anode suffers from poor morphological stability and Coulombic efficiency during cycling, especially in liquid electrolytes. In contrast to solid electrolytes, liquid electrolytes have the advantage of high ionic conductivity and good wetting of the anode, despite the lithium metal volume change during cycling. Rapid capacity fade due to inhomogeneous deposition and dissolution of lithium is the main hindrance to the successful utilization of the lithium metal anode in combination with liquid electrolytes. In this perspective, we discuss how experimental and theoretical insights can provide possible pathways for reversible cycling of twodimensional lithium metal. Therefore, we discuss improvements in the understanding of lithium metal nucleation, deposition, and stripping on the nanoscale. As the solid–electrolyte interphase (SEI) plays a key role in the lithium morphology, we discuss how the proper SEI design might allow stable cycling. We highlight recent advances in conventional and (localized) highly concentrated electrolytes in view of their respective SEIs. We also discuss artificial interphases and three-dimensional host frameworks, which show prospects of mitigating morphological instabilities and suppressing large shape change on the electrode level

Plastisol Foaming Process. Decomposition of the Foaming Agent, Polymer Behavior in the Corresponding Temperature Range and Resulting Foam Properties

The decomposition of azodicarbonamide, used as foaming agent in PVC - plasticizer (1/1) plastisols was studied by DSC. Nineteen different plasticizers, all belonging to the ester family, two being polymeric (polyadipates), were compared. The temperature of maximum decomposition rate (in anisothermal regime at 5 K min-1 scanning rate), ranges between 434 and 452 K. The heat of decomposition ranges between 8.7 and 12.5 J g -1. Some trends of variation of these parameters appear significant and are discussed in terms of solvent (matrix) and viscosity effects on the decomposition reactions. The shear modulus at 1 Hz frequency was determined at the temperature of maximum rate of foaming agent decomposition, and differs significantly from a sample to another. The foam density was determined at ambient temperature and the volume fraction of bubbles was used as criterion to judge the efficiency of the foaming process. The results reveal the existence of an optimal shear modulus of the order of 2 kPa that corresponds roughly to plasticizer molar masses of the order of 450 ± 50 g mol-1. Heavier plasticizers, especially polymeric ones are too difficult to deform. Lighter plasticizers such as diethyl phthalate (DEP) deform too easily and presumably facilitate bubble collapse

Epilepsy is related to theta band brain connectivity and network topology in brain tumor patients

<p>Abstract</p> <p>Background</p> <p>Both epilepsy patients and brain tumor patients show altered functional connectivity and less optimal brain network topology when compared to healthy controls, particularly in the theta band. Furthermore, the duration and characteristics of epilepsy may also influence functional interactions in brain networks. However, the specific features of connectivity and networks in tumor-related epilepsy have not been investigated yet. We hypothesize that epilepsy characteristics are related to (theta band) connectivity and network architecture in operated glioma patients suffering from epileptic seizures. Included patients participated in a clinical study investigating the effect of levetiracetam monotherapy on seizure frequency in glioma patients, and were assessed at two time points: directly after neurosurgery (t1), and six months later (t2). At these time points, magnetoencephalography (MEG) was recorded and information regarding clinical status and epilepsy history was collected. Functional connectivity was calculated in six frequency bands, as were a number of network measures such as normalized clustering coefficient and path length.</p> <p>Results</p> <p>At the two time points, MEG registrations were performed in respectively 17 and 12 patients. No changes in connectivity or network topology occurred over time. Increased theta band connectivity at t1 and t2 was related to a higher total number of seizures. Furthermore, higher number of seizures was related to a less optimal, more random brain network topology. Other factors were not significantly related to functional connectivity or network topology.</p> <p>Conclusions</p> <p>These results indicate that (pathologically) increased theta band connectivity is related to a higher number of epileptic seizures in brain tumor patients, suggesting that theta band connectivity changes are a hallmark of tumor-related epilepsy. Furthermore, a more random brain network topology is related to greater vulnerability to seizures. Thus, functional connectivity and brain network architecture may prove to be important parameters of tumor-related epilepsy.</p

The Connectome Visualization Utility: Software for Visualization of Human Brain Networks

In analysis of the human connectome, the connectivity of the human brain is collected from multiple imaging modalities and analyzed using graph theoretical techniques. The dimensionality of human connectivity data is high, and making sense of the complex networks in connectomics requires sophisticated visualization and analysis software. The current availability of software packages to analyze the human connectome is limited. The Connectome Visualization Utility (CVU) is a new software package designed for the visualization and network analysis of human brain networks. CVU complements existing software packages by offering expanded interactive analysis and advanced visualization features, including the automated visualization of networks in three different complementary styles and features the special visualization of scalar graph theoretical properties and modular structure. By decoupling the process of network creation from network visualization and analysis, we ensure that CVU can visualize networks from any imaging modality. CVU offers a graphical user interface, interactive scripting, and represents data uses transparent neuroimaging and matrix-based file types rather than opaque application-specific file formats