Dynamic regulation of Ero1 and peroxiredoxin 4 localization in the secretory pathway

In the early secretory compartment (ESC), a network of chaper- ones and enzymes assists oxidative folding of nascent proteins. Ero1 flavoproteins oxidize protein disulfide isomerase (PDI), gen- erating H2O2 as a byproduct. Peroxiredoxin 4 (Prx4) can utilize luminal H2O2 to oxidize PDI, thus favoring oxidative folding while limiting oxidative stress. Interestingly, neither ER oxidase contains known ER retention signal(s), raising the question of how cells pre- vent their secretion. Here we show that the two proteins share sim- ilar intracellular localization mechanisms. Their secretion is pre- vented by sequential interactions with PDI and ERp44, two resident proteins of the ESC-bearing KDEL-like motifs. PDI binds preferentially Ero1 , whereas ERp44 equally retains Ero1 and Prx4. The different binding properties of Ero1 and Prx4 increase the robustness of ER redox homeostasis

Reduction of cytochrome C oxidase during vasovagal hypoxia-ischemia in human adult brain: a case study

Near-infrared spectroscopy (NIRS)-derived measurement of oxidized cytochrome c oxidase concentration ([oxCCO]) has been used as an assessment of the adequacy of cerebral oxygen delivery. We report a case in which a reduction in conscious level was associated with a reduction in [oxCCO]. Hypoxaemia was induced in a 31-year-old, healthy male subject as part of an ongoing clinical study. Midway through the hypoxaemic challenge, the subject experienced an unexpected vasovagal event with bradycardia, hypotension and reduced cerebral blood flow (middle cerebral artery blood flow velocity decrease from 70 to 30 cm s(-1)) that induced a brief reduction in conscious level. An associated decrease in [oxCCO] was observed at 35 mm (-1.6 μM) but only minimal change (-0.1 μM) at 20-mm source-detector separation. A change in optical scattering was observed, but path length remained unchanged. This unexpected physiological event provides an unusual example of a severe reduction in cerebral oxygen delivery and is the first report correlating change in clinical status with changes in [oxCCO]

Pinning of spiral fluxons by giant screw dislocations in YBa_2Cu_3O_7 single crystals: Josephson analog of the fishtail effect

By using a highly sensitive homemade AC magnetic susceptibility technique, the magnetic flux penetration has been measured in YBa_2Cu_3O_7 single crystals with giant screw dislocations (having the structure of the Archimedean spirals) exhibiting a=3 spiral turnings, the pitch b=18.7 microns and the step height c=1.2nm (the last parameter is responsible for creation of extended weak-link structure around the giant defects). The magnetic field applied parallel to the surface enters winding around the weak-link regions of the screw in the form of the so-called spiral Josephson fluxons characterized by the temperature dependent pitch b_f(T). For a given temperature, a stabilization of the fluxon structure occurs when b_f(T) matches b (meaning an optimal pinning by the screw dislocations) and manifests itself as a pronounced low-field peak in the dependence of the susceptibility on magnetic field (applied normally to the surface) in the form resembling the high-field (Abrikosov) fishtail effect.Comment: see also http://www.jetpletters.ac.ru/ps/1886/article_28701.shtm

Structure optimization effects on the electronic properties of Bi2_2Sr2_2CaCu2_2O8_8

We present detailed first-principles calculations for the normal state electronic properties of the high T$_C$ superconductor Bi$_2$Sr$_2$CaCu$_2$O$_8$, by means of the linearized augmented plane wave (LAPW) method within the framework of density functional theory (DFT). As a first step, the body centered tetragonal (BCT) cell has been adopted, and optimized regarding its volume, $c/a$ ratio and internal atomic positions by total energy and force minimizations. The full optimization of the BCT cell leads to small but visible changes in the topology of the Fermi surface, rounding the shape of CuO$_2$ barrels, and causing both the BiO bands, responsible for the pockets near the \textit{\=M} 2D symmetry point, to dip below the Fermi level. We have then studied the influence of the distortions in the BiO plane observed in nature by means of a $\sqrt{2}\times\sqrt{2}$ orthorhombic cell (AD-ORTH) with $Bbmb$ space group. Contrary to what has been observed for the Bi-2201 compound, we find that for Bi-2212 the distortion does not sensibly shift the BiO bands which retain their metallic character. As a severe test for the considered structures we present Raman-active phonon frequencies ($q = 0$) and eigenvectors calculated within the frozen-phonon approximation. Focussing on the totally symmetric A$_{g}$ modes, we observe that for a reliable attribution of the peaks observed in Raman experiments, both $c$- and a-axis vibrations must be taken into account, the latter being activated by the in-plane orthorhombic distortion.Comment: 22 pages, 4 figure

Aminoacid zwitterions in solution : Geometric, energetic, and vibrational analysis using density functional theory-continuum model calculations

Glycine and alanine aminoacids chemistry in solution is explored using a hybrid three parameters density functional (B3PW91) together with a continuum model. Geometries, energies, and vibrational spectra of glycine and alanine zwitterions are studied at the B3PW91/6-31+G∗∗ level and the results compared with those obtained at the HF and MP2/6-31+G∗∗ levels. Solvents effects are incorporated by means of an ellipsoidal cavity model with a multipolar expansion (up to sixth order) of the solute’s electrostatic potential. Our results confirm the validity of the B3PW91 functional for studying aminoacid chemistry in solution. Taking into account the more favorable scaling behavior of density functional techniques with respect to correlated ab initio methods these studies could be extended to larger [email protected] ; [email protected]