Overexpression of Na+/Mg2+ exchanger SLC41A1 attenuates pro-survival signaling

The Na+/Mg2+ exchanger SLC41A1 (A1), a key component of intracellular Mg homeostasis (IMH), is the major cellular Mg2+ efflux system, and its overexpression decreases [Mg2+]intracellular. IMH plays an important role in the regulation of many cellular processes, including cellular signaling. However, whether the overexpression of A1 and the consequent drop of [Mg2+]i impact on intracellular signaling is unknown. To examine the latter, we utilized dynamic mass redistribution (DMR) assay, PathScan® RTK signaling antibody (PRSA) array, confirmatory Western blot (WB) analyses of phosphorylation of kinases selected by PRSA, and mag-fura 2-assisted fast filter spectrometry (FFS). We demonstrate here that the overexpression of A1 quantitatively and qualitatively changes the DMR signal evoked by the application of PAR-1-selective activating peptide and/or by changing [Mg2+]extracellular in HEK293 cells. PRSA profiling of the phosphorylation of important signaling nodes followed by confirmatory WB has revealed that, in HEK293 cells, A1 overexpression significantly attenuates the phosphorylation of Akt/PKB on Thr308 and/or Ser473 and of Erk1/2 on Thr202/Tyr204 in the presence of 0 or 1 mM (physiological) Mg2+ in the bath solution. The latter is also true for SH-SY5Y and HeLa cells. Overexpression of A1 in HEK293 cells significantly lowers [Mg2+]i in the presence of [Mg2+]e = 0 or 1 mM. This correlates with the observed attenuation of prosurvival Akt/PKB – Erk1/2 signaling in these cells. Thus, A1 expression status and [Mg2+]e (and consequently also [Mg2+]i) modulate the complex physiological fingerprint of the cell and influence the activity of kinases involved in anti-apoptotic and, hence, pro-survival events in cells

Energy-momentum balance in quantum dielectrics

We calculate the energy-momentum balance in quantum dielectrics such as Bose-Einstein condensates. In agreement with the experiment [G. K. Campbell et al. Phys. Rev. Lett. 94, 170403 (2005)] variations of the Minkowski momentum are imprinted onto the phase, whereas the Abraham tensor drives the flow of the dielectric. Our analysis indicates that the Abraham-Minkowski controversy has its root in the Roentgen interaction of the electromagnetic field in dielectric media

Two-Dimensional Magnetic Resonance Tomographic Microscopy using Ferromagnetic Probes

We introduce the concept of computerized tomographic microscopy in magnetic resonance imaging using the magnetic fields and field gradients from a ferromagnetic probe. We investigate a configuration where a two-dimensional sample is under the influence of a large static polarizing field, a small perpendicular radio-frequency field, and a magnetic field from a ferromagnetic sphere. We demonstrate that, despite the non-uniform and non-linear nature of the fields from a microscopic magnetic sphere, the concepts of computerized tomography can be applied to obtain proper image reconstruction from the original spectral data by sequentially varying the relative sample-sphere angular orientation. The analysis shows that the recent proposal for atomic resolution magnetic resonance imaging of discrete periodic crystal lattice planes using ferromagnetic probes can also be extended to two-dimensional imaging of non-crystalline samples with resolution ranging from micrometer to Angstrom scales.Comment: 9 pages, 11 figure

Quantized Roentgen Effect in Bose-Einstein Condensates

A classical dielectric moving in a charged capacitor can create a magnetic field (Roentgen effect). A quantum dielectric, however, will not produce a magnetization, except at vortices. The magnetic field outside the quantum dielectric appears as the field of quantized monopoles

States insensitive to the Unruh effect in multi-level detectors

We give a general treatment of the spontaneous excitation rates and the non-relativistic Lamb shift of constantly accelerated multi-level atoms as a model for multi-level detectors. Using a covariant formulation of the dipole coupling between the atom and the electromagnetic field we show that new Raman-like transitions can be induced by the acceleration. Under certain conditions these transitions can lead to stable ground and excited states which are not affected by the non inertial motion. The magnitude of the Unruh effect is not altered by multi-level effects. Both the spontaneous excitation rates and the Lamb shift are not within the range of measurability.Comment: 9 Pages, late

Dietary Mg2+ Intake and the Na+/Mg2+ Exchanger SLC41A1 Influence Components of Mitochondrial Energetics in Murine Cardiomyocytes

Cardiomyocytes are among the most energy-intensive cell types. Interplay between the components of cellular magnesium (Mg) homeostasis and energy metabolism in cardiomyocytes is poorly understood. We have investigated the effects of dietary Mg content and presence/functionality of the Na+/Mg2+ exchanger SLC41A1 on enzymatic functions of selected constituents of the Krebs cycle and complexes of the electron transport chain (ETC). The activities of aconitate hydratase (ACON), isocitrate dehydrogenase (ICDH), α-ketoglutarate dehydrogenase (KGDH), and ETC complexes CI–CV have been determined in vitro in mitochondria isolated from hearts of wild-type (WT) and Slc41a1−/− mice fed a diet with either normal or low Mg content. Our data demonstrate that both, the type of Mg diet and the Slc41a1 genotype largely impact on the activities of enzymes of the Krebs cycle and ETC. Moreover, a compensatory effect of Slc41a1−/− genotype on the effect of low Mg diet on activities of the tested Krebs cycle enzymes has been identified. A machine-learning analysis identified activities of ICDH, CI, CIV, and CV as common predictors of the type of Mg diet and of CII as suitable predictor of Slc41a1 genotype. Thus, our data delineate the effect of dietary Mg content and of SLC41A1 functionality on the energy-production in cardiac mitochondria

The fallacy of the equity-efficiency trade off: rethinking the efficient health system

In the health systems literature one can see discussions about the trade off between the equity achievable by the system and its efficiency. Essentially it is argued that as greater health equity is achieved, so the level of efficiency will diminish. This argument is borrowed from economics literature on market efficiency. In the application of the economic argument to health, however, serious errors have been made, because it is quite reasonable to talk of both health equity being a desirable output of a health system, and the efficient production of that output. In this article we discuss notions of efficiency, and the equity-efficiency trade off, before considering the implications of this for health systems

The Challenges, Opportunities, and Imperative of Structured Reporting in Medical Imaging

Despite dramatic innovation in medical imaging and information system technologies, the radiology report has remained stagnant for more than a century. Structured reporting was created in the hopes of addressing well-documented deficiencies in report content and organization but has largely failed in its adoption due to concerns over workflow and productivity. A number of political, economical, and clinical quality-centric initiatives are currently taking place within medicine which will dramatically change the medical landscape including Pay for Performance, Evidence-Based Medicine, and the Physician Quality Reporting Initiative. These will collectively enhance efforts to improve quality in reporting, stimulate new technology development, and counteract the impending threat of commoditization within radiology. Structured reporting offers a number of unique opportunities and advantages over traditional free text reporting and will provide a means for the radiology community to add value to its most important service deliverable the radiology report