Inhibition of Casein Kinase 2 Modulates XBP1-GRP78 Arm of Unfolded Protein Responses in Cultured Glial Cells

Stress signals cause abnormal proteins to accumulate in the endoplasmic reticulum (ER). Such stress is known as ER stress, which has been suggested to be involved in neurodegenerative diseases, diabetes, obesity and cancer. ER stress activates the unfolded protein response (UPR) to reduce levels of abnormal proteins by inducing the production of chaperon proteins such as GRP78, and to attenuate translation through the phosphorylation of eIF2α. However, excessive stress leads to apoptosis by generating transcription factors such as CHOP. Casein kinase 2 (CK2) is a serine/threonine kinase involved in regulating neoplasia, cell survival and viral infections. In the present study, we investigated a possible linkage between CK2 and ER stress using mouse primary cultured glial cells. 4,5,6,7-tetrabromobenzotriazole (TBB), a CK2-specific inhibitor, attenuated ER stress-induced XBP-1 splicing and subsequent induction of GRP78 expression, but was ineffective against ER stress-induced eIF2α phosphorylation and CHOP expression. Similar results were obtained when endogenous CK2 expression was knocked-down by siRNA. Immunohistochemical analysis suggested that CK2 was present at the ER. These results indicate CK2 to be linked with UPR and to resist ER stress by activating the XBP-1-GRP78 arm of UPR

Graphene-passivated nickel as an oxidation-resistant electrode for spintronics.

We report on graphene-passivated ferromagnetic electrodes (GPFE) for spin devices. GPFE are shown to act as spin-polarized oxidation-resistant electrodes. The direct coating of nickel with few layer graphene through a readily scalable chemical vapor deposition (CVD) process allows the preservation of an unoxidized nickel surface upon air exposure. Fabrication and measurement of complete reference tunneling spin valve structures demonstrate that the GPFE is maintained as a spin polarizer and also that the presence of the graphene coating leads to a specific sign reversal of the magneto-resistance. Hence, this work highlights a novel oxidation-resistant spin source which further unlocks low cost wet chemistry processes for spintronics devices.R.S.W. acknowledges funding from EPSRC (Doctoral training award). S.H. acknowledges funding from ERC Grant InsituNANO (Project Reference 279342). P.S. acknowledges the Institut Universitaire de France for junior fellowship support. This research was partially supported by the EU FP7 work programme under Grant GRAFOL (Project Reference 285275).This is the accepted manuscript. The final version is available from ACS at http://pubs.acs.org/doi/abs/10.1021/nn304424x

Polymorphic Signature of the Anti-inflammatory Activity of 2,2′- {[1,2-Phenylenebis(methylene)]bis(sulfanediyl)}bis(4,6- dimethylnicotinonitrile)

Weak noncovalent interactions are the basic forces in crystal engineering. Polymorphism in flexible molecules is very common, leading to the development of the crystals of same organic compounds with different medicinal and material properties. Crystallization of 2,2′- {[1,2-phenylenebis(methylene)]bis(sulfanediyl)}bis(4,6-dimethylnicotinonitrile) by evaporation at room temperature from ethyl acetate and hexane and from methanol and ethyl acetate gave stable polymorphs 4a and 4b, respectively, while in acetic acid, it gave metastable polymorph 4c. The polymorphic behavior of the compound has been visualized through singlecrystal X-ray and Hirshfeld analysis. These polymorphs are tested for anti-inflammatory activity via the complete Freund’s adjuvant-induced rat paw model, and compounds have exhibited moderate activities. Studies of docking in the catalytic site of cyclooxygenase-2 were used to identify potential anti-inflammatory lead compounds. These results suggest that the supramolecular aggregate structure, which is formed in solution, influences the solid state structure and the biological activity obtained upon crystallization

Conditions for the occurrence of acicular ferrite transformation in HSLA steels

For the class of steels collectively known as high strength low alloy (HSLA), an acicular ferrite (AF) microstructure produces an excellent combination of strength and toughness. The conditions for the occurrence of the AF transformation are, however, still unclear, especially the effects of austenite deformation and continuous cooling. In this research, a commercial HSLA steel was used and subjected to deformation via plane strain compression with strains ranging from 0 to 0.5 and continuous cooling at rates between 5 and 50 °C s −1 . Based on the results obtained from optical microscopy, scanning electron microscopy and electron backscattering diffraction mapping, the introduction of intragranular nucleation sites and the suppression of bainitic ferrite (BF) laths lengthening were identified as the two key requirements for the occurrence of AF transformation. Austenite deformation is critical to meet these two conditions as it introduces a high density of dislocations that act as intragranular nucleation sites and deformation substructures, which suppress the lengthening of BF laths through the mechanism of mechanical stabilisation of austenite. However, the suppression effect of austenite deformation is only observed under relatively slow cooling rates or high transformation temperatures, i.e., conditions where the driving force for advancing the transformation interface is not sufficient to overcome the austenite deformation substructures

On the mechanism of superelasticity in Gum metal

The deformation mechanisms of the beta-Ti alloy, Gum metal, were investigated with the aid of in situ synchrotron X-ray diffraction (SXRD) and transmission electron microscopy (TEM). SXRD showed that Gum metal undergoes it reversible stress-induced martensitic (alpha '') phase transformation. Oxygen increases the resistance to shear by increasing C' and limits the extent of alpha '' growth. Prior deformation aids alpha '' formation of by providing nuclei, such as {112} twins and stress-induced omega plates. The formation of twins and omega plates, both observed in TEM, are believed to be a result of a low G(111) in this alloy. Features similar to the "giant faults" seen previously were observed in TEM their formation is believed to be a result of {112} shear. (C) 2008 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved