Interaction of hemojuvelin with neogenin results in iron accumulation in human embryonic kidney 293 cells

Type 2 hereditary hemochromatosis (HH) or juvenile hemochromatosis is an early onset, genetically heterogeneous, autosomal recessive disorder of iron overload. Type 2A HH is caused by mutations in the recently cloned hemojuvelin gene (HJV; also called HFE2) (Papanikolaou, G., Samuels, M. E., Ludwig, E. H., MacDonald, M. L., Franchini, P. L., Dube, M. P., Andres, L., MacFarlane, J., Sakellaropoulos, N., Politou, M., Nemeth, E., Thompson, J., Risler, J. K., Zaborowska, C., Babakaiff, R., Radomski, C. C., Pape, T. D., Davidas, O., Christakis, J., Brissot, P., Lockitch, G., Ganz, T., Hayden, M. R., and Goldberg, Y. P. (2004) Nat. Genet. 36, 77–82), whereas Type 2B HH is caused by mutations in hepcidin. HJV is highly expressed in both skeletal muscle and liver. Mutations in HJV are implicated in the majority of diagnosed juvenile hemochromatosis patients. In this study, we stably transfected HJV cDNA into human embryonic kidney 293 cells and characterized the processing of HJV and its effect on iron homeostasis. Our results indicate that HJV is a glycosylphosphatidylinositol-linked protein and undergoes a partial autocatalytic cleavage during its intracellular processing. HJV co-immunoprecipitated with neogenin, a receptor involved in a variety of cellular signaling processes. It did not interact with the closely related receptor DCC (deleted in Colon Cancer). In addition, the HJV G320V mutant implicated in Type 2A HH did not co-immunoprecipitate with neogenin. Immunoblot analysis of ferritin levels and transferrin-55Fe accumulation studies indicated that the HJV-induced increase in intracellular iron levels in human embryonic kidney 293 cells is dependent on the presence of neogenin in the cells, thus linking these two proteins to intracellular iron homeostasis

Electronic structure and Magnetism in BaMn2_2As2_2 and BaMn2_2Sb2_2

We study the properties of ThCr$_2$Si$_2$ structure BaMn$_2$As$_2$ and BaMn$_2$Sb$_2$ using density functional calculations of the electronic and magnetic as well experimental measurements on single crystal samples of BaMn$_2$As$_2$. These materials are local moment magnets with moderate band gap antiferromagnetic semiconducting ground states. The electronic structures show substantial Mn - pnictogen hybridization, which stabilizes an intermediate spin configuration for the nominally $d^5$ Mn. The results are discussed in the context of possible thermoelectric applications and the relationship with the corresponding iron / cobalt / nickel compounds Ba(Fe,Co,Ni)$_2$As$_2$

Lessons from LIMK1 enzymology and their impact on inhibitor design

LIM domain kinase 1 (LIMK1) is a key regulator of actin dynamics. It is thereby a potential therapeutic target for the prevention of fragile X syndrome and amyotrophic lateral sclerosis. Herein, we use X-ray crystallography and activity assays to describe how LIMK1 accomplishes substrate specificity, to suggest a unique ‘rock-and-poke’ mechanism of catalysis and to explore the regulation of the kinase by activation loop phosphorylation. Based on these findings, a differential scanning fluorimetry assay and a RapidFire mass spectrometry activity assay were established, leading to the discovery and confirmation of a set of small-molecule LIMK1 inhibitors. Interestingly, several of the inhibitors were inactive towards the closely related isoform LIMK2. Finally, crystal structures of the LIMK1 kinase domain in complex with inhibitors (PF-477736 and staurosporine, respectively) are presented, providing insights into LIMK1 plasticity upon inhibitor binding

Time-resolved characterization of a pulsed discharge in a stationary bubble

In recent years, plasma generation in water has been proposed for the application of water treatment. The process efficiency is believed to be improved by the introduction of bubbles in the plasma active region. For further optimization, the initiating and developmental mechanisms of plasma inside bubbles need to be understood to a greater extent. In order to meet this necessity, we investigated pulsed electrical discharge inside a stationary bubble in water. This paper deals with the evolution of the discharge and of the bubble shape during discharge, investigated by electrical characterization and fast imaging. Only several microseconds after the application of the voltage pulse, plasma light is observed. Different phases are observed during plasma formation. The plasma is strongest at the bubble surface, causing the surrounding water to evaporate. This leads to both the formation of propagating streamers into the water and the expansion and collapse of the bubble. These observations show that plasma inside a bubble has the strongest activity at the bubble surface, making it attractive for water treatment

Cluster Variation Approach to the Random-Anisotropy Blume-Emery-Griffiths Model

The random--anisotropy Blume--Emery--Griffiths model, which has been proposed to describe the critical behavior of $^3$He--$^4$He mixtures in a porous medium, is studied in the pair approximation of the cluster variation method extended to disordered systems. Several new features, with respect to mean field theory, are found, including a rich ground state, a nonzero percolation threshold, a reentrant coexistence curve and a miscibility gap on the high $^3$He concentration side down to zero temperature. Furthermore, nearest neighbor correlations are introduced in the random distribution of the anisotropy, which are shown to be responsible for the raising of the critical temperature with respect to the pure and uncorrelated random cases and contribute to the detachment of the coexistence curve from the $\lambda$ line.Comment: 14 pages (plain TeX) + 12 figures (PostScript, appended), Preprint POLFIS-TH.02/9

Superconductivity in two-band systems with variable charge carrier density. The case of MgB2

The theory of thermodynamic properties of two-band superconductor with reduced density charge carriers is developed on the base of phonon superconducting mechanism with strong electron-phonon interaction. This theory is adapted to describe the behavior of critical temperature Tc, energy gaps Delta1, Delta2, and the relative jump of electron specific heat (Cs - Cn)/Cn in the point T = Tc along with the variation of charge carrier density in the compound MgB2 when substitutional impurities with different valence are introduced into the system. It is shown, that according to the filling mechanism of energy bands which overlap on Fermi surface, the quantities Tc, Delta1, Delta2 decrease when this compound is doped with electrons and remain constant or weakly change when the system is doped with holes. The theory qualitatively agrees with the experimental data. Also is shown that the consideration of inter- and intraband scattering of electrons on impurity potential improves this agreement.Comment: 19 pages, 6 figures, 1 table. to be published in JETP (first number 2007