When mFOLFIRINOX is coupled with aggressive surgery, high resection rates are possible even when the initial imaging shows locally advanced disease. Although data are still maturing, resection appears to offer at least a progression-free survival advantage.”
“Arenaviruses cause acute hemorrhagic fevers with high mortality. Entry of the virus into the host cell is mediated by the viral envelope glycoprotein, GPC. In contrast to other class I viral envelope glycoproteins, the mature GPC complex contains a cleaved stable signal peptide (SSP) in addition to the canonical receptor-binding (G1) and transmembrane fusion (G2) subunits. SSP is critical for
intracellular transport of the GPC complex to the cell surface and for its membrane-fusion activity. Previous studies selleckchem have suggested that SSP is retained in GPC through interaction with a zinc-binding domain (ZBD) in the cytoplasmic tail of G2. Here Silmitasertib ic50 we used NMR spectroscopy to determine the structure of Junin virus (JUNV) ZBD (G2 residues 445-485) and investigate its interaction with a conserved Cys residue (Cys-57) in SSP. We show that JUNV ZBD displays a novel fold containing two
zinc ions. One zinc ion is coordinated by His-447, His-449, Cys-455, and His-485. The second zinc ion is coordinated by His-459, Cys-467, and Cys-469 and readily accepts Cys-57 from SSP as the fourth ligand. Our studies describe the structural basis for retention
of the unique SSP subunit and suggest a mechanism whereby SSP is positioned in the GPC complex to modulate pH-dependent membrane fusion.”
“The infrared spectrum of the nu(3) band of an OCS (carbonyl sulfide) molecule embedded inside pure He-3 droplets of about 12 x 10(3) atoms reported in 1998 [S. Grebenev, J. P. Toennies, and A. F. Vilesov, Science 279, 2083 (1998)] is carefully evaluated. The spectrum, which consists of a broad central peak and a distinct shoulder at lower energy, was analyzed by assuming unresolved rotational line structure of either a linear or a symmetric top. In each case the spectrum was fitted using either Lorentzian or Gaussian peak shapes with a preassigned fixed temperature of 0.15 K or a best fit temperature. Many of the fits describe the spectra nearly equally well and indicate broad R(0), R(1), drug discovery and P(1) peaks but no Q-branch, a moment of inertia which is about a factor six greater than for the free molecule, and a temperature of 0.07 +/- 0.06 K which is significantly less than 0.15 K determined for mixed He-3/He-4 droplets. The increased moment of inertia is consistent with about 11 attached He-3 atoms which take part in the end-over-end rotations of the chromophore. The large line widths are attributed to creation of particle-hole pair excitations in the fermionic droplets. (C) 2012 American Institute of Physics. [http://dx.doi.org/10.1063/1.