Obamacare: The Birds Still Sing as Freedom Erodes

The article discusses the impact of the U.S. health care bill signed into law by U.S. President Barack Obama in 2010. When provisions begin to take effect in 2014, government spending will reportedly increase such that it would expand the deficit and Americans\u27 freedom will be reduced. The new system turns health insurance companies into government agents with the government determining the premiums, benefits and types of policies to be issued

Increased leukotriene C 4 and vasogenic edema surrounding brain tumors in humans

Leukotrines are pharmacologically active compounds that promote vascular permeability. In this study we sought to determine whether tissue leukotriene–like immunoreactivity was increased in intracranial tumors associated with peritumoral edema. In 20 patients undergoing craniotomy tissue specimens were immediately frozen after removal and tissue leukotriene C 4 levels were determined by radioimmunoassay. An index of peritumoral edema was estimated from preoperative contrast-enhanced computed tomographic scans. There was a significant correlation between brain edema and tissue leukotriene levels ( p < 0.003). Metastatic tumors (n = 8) had the highest leukotriene C 4 level at 13.8 ± 8.5 pg/mg tissue (mean ± SE) and the highest index of edema 5.7 ± 1.8. The mean leukotriene C 4 level in the gliomas (n + 5) ws 6.2 ± 2.3 pg/mg tissue and the edema index was 2.1 ± 0.6. There was no edema and no neoplasma in he temporal lobes removed for seizure (n + 2), and their level of leukotriene C 4 was 0.4 ± 0.1 pg/mg tissue. The formation of leukotriene C 4 is stimulated by intracranial tumors. Leukotrienes increase blood–brain barrier permeability and may be important in the formation of vasogenic edema surrounding tumors.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/50315/1/410190613_ftp.pd

Notch signaling regulates metabolic heterogeneity in glioblastoma stem cells.

Glioblastoma (GBM) stem cells (GSCs) reside in both hypoxic and vascular microenvironments within tumors. The molecular mechanisms that allow GSCs to occupy such contrasting niches are not understood. We used patient-derived GBM cultures to identify GSC subtypes with differential activation of Notch signaling, which co-exist in tumors but occupy distinct niches and match their metabolism accordingly. Multipotent GSCs with Notch pathway activation reside in perivascular niches, and are unable to entrain anaerobic glycolysis during hypoxia. In contrast, most CD133-expressing GSCs do not depend on canonical Notch signaling, populate tumors regardless of local vascularity and selectively utilize anaerobic glycolysis to expand in hypoxia. Ectopic activation of Notch signaling in CD133-expressing GSCs is sufficient to suppress anaerobic glycolysis and resistance to hypoxia. These findings demonstrate a novel role for Notch signaling in regulating GSC metabolism and suggest intratumoral GSC heterogeneity ensures metabolic adaptations to support tumor growth in diverse tumor microenvironments

A multi-parametric flow cytometric assay to analyze DNA–protein interactions

Interactions between DNA and transcription factors (TFs) guide cellular function and development, yet the complexities of gene regulation are still far from being understood. Such understanding is limited by a paucity of techniques with which to probe DNA–protein interactions. We have devised magnetic protein immobilization on enhancer DNA (MagPIE), a simple, rapid, multi-parametric assay using flow cytometric immunofluorescence to reveal interactions among TFs, chromatin structure and DNA. In MagPIE, synthesized DNA is bound to magnetic beads, which are then incubated with nuclear lysate, permitting sequence-specific binding by TFs, histones and methylation by native lysate factors that can be optionally inhibited with small molecules. Lysate protein–DNA binding is monitored by flow cytometric immunofluorescence, which allows for accurate comparative measurement of TF-DNA affinity. Combinatorial fluorescent staining allows simultaneous analysis of sequence-specific TF-DNA interaction and chromatin modification. MagPIE provides a simple and robust method to analyze complex epigenetic interactions in vitro

The VLA/ALMA Nascent Disk and Multiplicity (VANDAM) Survey of Orion Protostars IV. Unveiling the Embedded Intermediate-Mass Protostar and Disk within OMC2-FIR3/HOPS-370

We present ALMA (0.87~mm and 1.3~mm) and VLA (9~mm) observations toward the candidate intermediate-mass protostar OMC2-FIR3 (HOPS-370; L$_{bol}$~314~L$_{\odot}$) at $\sim$0.1" (40~au) resolution for the continuum emission and ~0.25" (100 au) resolution of nine molecular lines. The dust continuum observed with ALMA at 0.87~mm and 1.3~mm resolve a near edge-on disk toward HOPS-370 with an apparent radius of ~100 au. The VLA observations detect both the disk in dust continuum and free-free emission extended along the jet direction. The ALMA observations of molecular lines (H$_2$CO, SO, CH$_3$OH, $^{13}$CO, C$^{18}$O, NS, and H$^{13}$CN) reveal rotation of the apparent disk surrounding HOPS-370 orthogonal to the jet/outflow direction. We fit radiative transfer models to both the dust continuum structure of the disk and molecular line kinematics of the inner envelope and disk for the H$_2$CO, CH$_3$OH, NS, and SO lines. The central protostar mass is determined to be $\sim$2.5 M_sun with a disk radius of $\sim$94~au, when fit using combinations of the H$_2$CO, CH$_3$OH, NS, and SO lines, consistent with an intermediate-mass protostar. Modeling of the dust continuum and spectral energy distribution (SED) yields a disk mass of 0.035~M$_{\odot}$ (inferred dust+gas) and a dust disk radius of 62~au, thus the dust disk may have a smaller radius than the gas disk, similar to Class II disks. In order to explain the observed luminosity with the measured protostar mass, HOPS-370 must be accreting at a rate between 1.7 and 3.2$\times$10$^{-5}$~M$_{\odot}$~yr$^{-1}$.Comment: Accepted to ApJ; 51 pages, 12 Figures, 7 Table