Site testing in summer at Dome C, Antarctica

We present summer site testing results based on DIMM data obtained at Dome C, Antarctica. These data have been collected on the bright star Canopus during two 3-months summer campaigns in 2003-2004 and 2004-2005. We performed continuous monitoring of the seeing a nd the isoplanatic angle in the visible. We found a median seeing of 0.54 \arcsec and a median isoplanatic angle of 6.8 \arcsec. The seeing appears to have a deep minimum around 0.4 \arcsec almost every day in late afternoon

A Serum Factor Induces Insulin-Independent Translocation of GLUT4 to the Cell Surface which Is Maintained in Insulin Resistance

In response to insulin, glucose transporter GLUT4 translocates from intracellular compartments towards the plasma membrane where it enhances cellular glucose uptake. Here, we show that sera from various species contain a factor that dose-dependently induces GLUT4 translocation and glucose uptake in 3T3-L1 adipocytes, human adipocytes, myoblasts and myotubes. Notably, the effect of this factor on GLUT4 is fully maintained in insulin-resistant cells. Our studies demonstrate that the serum-induced increase in cell surface GLUT4 levels is not due to inhibition of its internalization and is not mediated by insulin, PDGF, IGF-1, or HGF. Similarly to insulin, serum also augments cell surface levels of GLUT1 and TfR. Remarkably, the acute effect of serum on GLUT4 is largely additive to that of insulin, while it also sensitizes the cells to insulin. In accordance with these findings, serum does not appear to activate the same repertoire of downstream signaling molecules that are implicated in insulin-induced GLUT4 translocation. We conclude that in addition to insulin, at least one other biological proteinaceous factor exists that contributes to GLUT4 regulation and still functions in insulin resistance. The challenge now is to identify this factor

Abnormal Changes in NKT Cells, the IGF-1 Axis, and Liver Pathology in an Animal Model of ALS

Amyotrophic lateral sclerosis (ALS) is a rapidly progressing fatal neurodegenerative disorder characterized by the selective death of motor neurons (MN) in the spinal cord, and is associated with local neuroinflammation. Circulating CD4+ T cells are required for controlling the local detrimental inflammation in neurodegenerative diseases, and for supporting neuronal survival, including that of MN. T-cell deficiency increases neuronal loss, while boosting T cell levels reduces it. Here, we show that in the mutant superoxide dismutase 1 G93A (mSOD1) mouse model of ALS, the levels of natural killer T (NKT) cells increased dramatically, and T-cell distribution was altered both in lymphoid organs and in the spinal cord relative to wild-type mice. The most significant elevation of NKT cells was observed in the liver, concomitant with organ atrophy. Hepatic expression levels of insulin-like growth factor (IGF)-1 decreased, while the expression of IGF binding protein (IGFBP)-1 was augmented by more than 20-fold in mSOD1 mice relative to wild-type animals. Moreover, hepatic lymphocytes of pre-symptomatic mSOD1 mice were found to secrete significantly higher levels of cytokines when stimulated with an NKT ligand, ex-vivo. Immunomodulation of NKT cells using an analogue of α-galactosyl ceramide (α-GalCer), in a specific regimen, diminished the number of these cells in the periphery, and induced recruitment of T cells into the affected spinal cord, leading to a modest but significant prolongation of life span of mSOD1 mice. These results identify NKT cells as potential players in ALS, and the liver as an additional site of major pathology in this disease, thereby emphasizing that ALS is not only a non-cell autonomous, but a non-tissue autonomous disease, as well. Moreover, the results suggest potential new therapeutic targets such as the liver for immunomodulatory intervention for modifying the disease, in addition to MN-based neuroprotection and systemic treatments aimed at reducing oxidative stress

Computational Modeling and Analysis of Insulin Induced Eukaryotic Translation Initiation

Insulin, the primary hormone regulating the level of glucose in the bloodstream, modulates a variety of cellular and enzymatic processes in normal and diseased cells. Insulin signals are processed by a complex network of biochemical interactions which ultimately induce gene expression programs or other processes such as translation initiation. Surprisingly, despite the wealth of literature on insulin signaling, the relative importance of the components linking insulin with translation initiation remains unclear. We addressed this question by developing and interrogating a family of mathematical models of insulin induced translation initiation. The insulin network was modeled using mass-action kinetics within an ordinary differential equation (ODE) framework. A family of model parameters was estimated, starting from an initial best fit parameter set, using 24 experimental data sets taken from literature. The residual between model simulations and each of the experimental constraints were simultaneously minimized using multiobjective optimization. Interrogation of the model population, using sensitivity and robustness analysis, identified an insulin-dependent switch that controlled translation initiation. Our analysis suggested that without insulin, a balance between the pro-initiation activity of the GTP-binding protein Rheb and anti-initiation activity of PTEN controlled basal initiation. On the other hand, in the presence of insulin a combination of PI3K and Rheb activity controlled inducible initiation, where PI3K was only critical in the presence of insulin. Other well known regulatory mechanisms governing insulin action, for example IRS-1 negative feedback, modulated the relative importance of PI3K and Rheb but did not fundamentally change the signal flow

Differential protein phosphorylation in 3T3-L1 adipocytes in response to insulin versus platelet-derived growth factor

Insulin regulates glucose metabolism in adipocytes via a phosphatidylinositide 3-kinase (PI3K)-dependent pathway that appears to involve protein phosphorylation. However, the generation of phosphoinositides is not sufficient for insulin action, and it has been suggested that insulin regulation of glucose metabolism may involve both PI3K-dependent and -independent pathways, the latter being insulin specific. To test this hypothesis, we have designed a phosphoprotein screen to study insulin-specific phosphoproteins that may be either downstream or in parallel to PI3K. Nineteen insulin-regulated phosphospots were detected in the cytosol and high speed pellet fractions, only six of which were significantly regulated by platelet-derived growth factor. Importantly, almost all (92%) of the insulin-specific phosphoproteins identified using this approach were sensitive to the PI3K inhibitor wortmannin. Thus, we obtained no evidence for an insulin-specific, PI3K-independent signaling pathway. A large proportion (62%) of the insulin-specific phosphoproteins were enriched in the same high speed pellet fraction to which PI3K was recruited in response to insulin. Thus, our data suggest that insulin specifically stimulates the phosphorylation of a novel subset of downstream targets and this may in part be because of the unique localization of PI3K in response to insulin in adipocytes

Effects of water soaking and/or sodium polystyrene sulfonate addition on potassium content of foods

In this study, we determined, by atomic absorption spectrophotometry, the potassium amount leached by soaking or boiling foods identified by children suffering from chronic renal failure as "pleasure food' and that they cannot eat because of their low-potassium diet, and evaluated whether addition of sodium polystyrene sulfonate resin (i.e. Kayexalate (R)) during soaking or boiling modulated potassium loss. A significant amount of potassium content was removed by soaking (16% for chocolate and potato, 26% for apple, 37% for tomato and 41% for banana) or boiling in a large amount of water (73% for potato). Although Kayexalate (R) efficiently dose-dependently removed potassium from drinks (by 48% to 73%), resin addition during soaking or boiling did not eliminate more potassium from solid foods. Our results therefore provide useful information for dietitians who elaborate menus for people on potassium-restricted diets and would give an interesting alternative to the systematic elimination of all potassium-rich foods from their diet

Direct measurement of the formation height difference of the 630 nm Fe I solar lines

Context. Spectral lines formed over a limited height range in either a stellar or planetary atmosphere provide us with information about the physical conditions within this height range. In this context, an important quantity is the so-called line formation depth. It is usually determined from numerical calculation of the atmospheric opacity in the line of interest and then converted into geometrical depth by using atmospheric models. Aims. We develop a radically different approach, which allows us to measure directly line formation depths from spectroscopic observations without relying on assumptions about an atmospheric model. This method requires spatially resolved observations, which up to now have been available only for solar or planetary studies. We apply this method to images of the solar granulation. Methods. The method was presented and tested numerically in previous papers. It is based on the measurement of the perspective shift between images at different wavelengths, formed at different heights, when they are observed away from disk center. Because of the Fourier transform properties, this shift gives rise to a deterministic linear phase term in the cross spectrum of the images. Results. The method is applied to observations of solar quiet regions performed with the SOT spectropolarimeter on HINODE in the Fe