Cell surface localization of tissue transglutaminase is dependent on a fibronectin-binding site in its N-terminal beta-sandwich domain

Increasing evidence indicates that tissue transglutaminase (tTG) plays a role in the assembly and remodeling of extracellular matrices and promotes cell adhesion. Using an inducible system we have previously shown that tTG associates with the extracellular matrix deposited by stably transfected 3T3 fibroblasts overexpressing the enzyme. We now show by confocal microscopy that tTG colocalizes with pericellular fibronectin in these cells, and by immunogold electron microscopy that the two proteins are found in clusters at the cell surface. Expression vectors encoding the full-length tTG or a N-terminal truncated tTG lacking the proposed fibronectin-binding site (fused to the bacterial reporter enzyme β-galactosidase) were generated to characterize the role of fibronectin in sequestration of tTG in the pericellular matrix. Enzyme-linked immunosorbent assay style procedures using extracts of transiently transfected COS-7 cells and immobilized fibronectin showed that the truncation abolished fibronectin binding. Similarly, the association of tTG with the pericellular matrix of cells in suspension or with the extracellular matrix deposited by cell monolayers was prevented by the truncation. These results demonstrate that tTG binds to the pericellular fibronectin coat of cells via its N-terminal β-sandwich domain and that this interaction is crucial for cell surface association of tTG

Anti-transglutaminase 6 antibodies in children and young adults with cerebral palsy.

Objectives. We have previously reported a high prevalence of gluten-related serological markers (GRSM) in children and young adults with cerebral palsy (CP). The majority had no enteropathy to suggest coeliac disease (CD). Antibodies against transglutaminase 6 (anti-TG6) represent a new marker associated with gluten-related neurological dysfunction. The aim of this study was to investigate the prevalence of anti-TG6 antibodies in this group of individuals with an early neurological injury resulting in CP. Materials and Methods. Sera from 96 patients with CP and 36 controls were analysed for IgA/IgG class anti-TG6 by ELISA. Results. Anti-TG6 antibodies were found in 12/96 (13%) of patients with CP compared to 2/36 (6%) in controls. The tetraplegic subgroup of CP had a significantly higher prevalence of anti-TG6 antibodies 6/17 (35%) compared to the other subgroups and controls. There was no correlation of anti-TG6 autoantibodies with seropositivity to food proteins including gliadin. Conclusions. An early brain insult and associated inflammation may predispose to future development of TG6 autoimmunity

Deterministic spatio-temporal control of nano-optical fields in optical antennas and nano transmission lines

We show that pulse shaping techniques can be applied to tailor the ultrafast temporal response of the strongly confined and enhanced optical near fields in the feed gap of resonant optical antennas (ROAs). Using finite-difference time-domain (FDTD) simulations followed by Fourier transformation, we obtain the impulse response of a nano structure in the frequency domain, which allows obtaining its temporal response to any arbitrary pulse shape. We apply the method to achieve deterministic optimal temporal field compression in ROAs with reduced symmetry and in a two-wire transmission line connected to a symmetric dipole antenna. The method described here will be of importance for experiments involving coherent control of field propagation in nanophotonic structures and of light-induced processes in nanometer scale volumes.Comment: 5 pages, 5 figure

Experimental time-resolved photoemission and ab initio study of lifetimes of excited electrons in Mo and Rh

We have studied the relaxation dynamics of optically excited electrons in molybdenum and rhodium by means of time resolved two-photon photoemission spectroscopy (TR-2PPE) and ab initio electron self-energy calculations performed within the GW and GW+T approximations. Both theoretical approaches reproduce qualitatively the experimentally observed trends and differences in the lifetimes of excited electrons in molybdenum and rhodium. For excitation energies exceeding the Fermi energy by more than 1 eV, the GW+T theory yields lifetimes in quantitative agreement with the experimental results. As one of the relevant mechanisms causing different excited state lifetime in Mo and Rh we identify the occupation of the 4d bands. An increasing occupation of the 4d bands results in an efficient decrease of the lifetime even for rather small excitation energies of a few 100 meV.Comment: 8 pages, 10 figure

Broadband enhancement of the magneto-optical activity of hybrid Au loaded Bi:YIG

We unravel the underlying near-field mechanism of the enhancement of the magneto-optical activity of bismuth-substituted yttrium iron garnet films (Bi:YIG) loaded with gold nanoparticles. The experimental results show that the embedded gold nanoparticles lead to a broadband enhancement of the magneto-optical activity with respect to the activity of the bare Bi:YIG films. Full vectorial near- and far-field simulations demonstrate that this broadband enhancement is the result of a magneto-optically enabled cross-talking of orthogonal localized plasmon resonances. Our results pave the way to the on-demand design of the magneto-optical properties of hybrid magneto-plasmonic circuitry.Comment: 6 Pages, 3 Figure

Comparison in the immunological properties of Borrelia burgdorferi isolates from Ixodes ricinus derived from three endemic areas in Switzerland

Borrelia burgdorferi isolates were obtained from Ixodes ricinus from three sites in Switzerland. They were examined by SDS-PAGE and immunoblotting. The phenotypes, in respect of three outer surface proteins (Osp), differed between the sites of collection. In site 1, most isolates had an OspA of 31 kDa and an OspB of 34 kDa: in site 2, isolates presenting an OspA of 33 kDa dominated and in site 3, the isolates with an OspA of 32 kDa and an OspB of 35 kDa were most frequent. This distribution differed significantly. About half of the isolates from sites 1 and 3 reacted with anti-OspA monoclonal antibody H5332 compared to 29% from site 2. Site 1 isolates reacted significantly more frequently (81 %) with another anti-OspA monoclonal antibody LA-31 than isolates from site 3 (P < 0·0001). These findings have implications for the epidemiology of Lyme borreliosis, for the further development of serodiagnostic reagents and for the development of a vaccin

Spin-flip processes and ultrafast magnetization dynamics in Co - unifying the microscopic and macroscopic view of femtosecond magnetism

The femtosecond magnetization dynamics of a thin cobalt film excited with ultrashort laser pulses has been studied using two complementary pump-probe techniques, namely spin-, energy- and time-resolved photoemission and time-resolved magneto-optical Kerr effect. Combining the two methods it is possible to identify the microscopic electron spin-flip mechanisms responsible for the ultrafast macroscopic magnetization dynamics of the cobalt film. In particular, we show that electron-magnon excitation does not affect the overall magnetization even though it is an efficient spin-flip channel on the sub-200 fs timescale. Instead we find experimental evidence for the relevance of Elliott-Yafet type spin-flip processes for the ultrafast demagnetization taking place on a time scale of 300 fs.Comment: 12 pages, 3 figures; accepted by Physical Review Letter

Structure and electronic properties of the (3×3\sqrt{3}\times \sqrt{3})R30∘R30^{\circ} SnAu2_2/Au(111) surface alloy

We have investigated the atomic and electronic structure of the ($\sqrt{3}\times \sqrt{3}$)$R30^{\circ}$ SnAu$_2$/Au(111) surface alloy. Low energy electron diffraction and scanning tunneling microscopy measurements show that the native herringbone reconstruction of bare Au(111) surface remains intact after formation of a long range ordered ($\sqrt{3}\times \sqrt{3}$)$R30^{\circ}$ SnAu$_2$2/Au(111) surface alloy. Angle-resolved photoemission and two-photon photoemission spectroscopy techniques reveal Rashba-type spin-split bands in the occupied valence band with comparable momentum space splitting as observed for the Au(111) surface state, but with a hole-like parabolic dispersion. Our experimental findings are compared with density functional theory (DFT) calculation that fully support our experimental findings. Taking advantage of the good agreement between our DFT calculations and the experimental results, we are able to extract that the occupied Sn-Au hybrid band is of (s, d)-orbital character while the unoccupied Sn-Au hybrid bands are of (p, d)-orbital character. Hence, we can conclude that the Rashba-type spin splitting of the hole-like Sn-Au hybrid surface state is caused by the significant mixing of Au d- to Sn s-states in conjunction with the strong atomic spin-orbit coupling of Au, i.e., of the substrate.Comment: Copyright: https://journals.aps.org/authors/transfer-of-copyright-agreement; All copyrights by AP

Mutations in TGM6 induce the unfolded protein response in SCA35

Spinocerebellar ataxia type 35 (SCA35) is a rare autosomal-dominant neurodegenerative disease caused by mutations in the TGM6 gene, which codes for transglutaminase 6 (TG6). Mutations in TG6 induce cerebellar degeneration by an unknown mechanism. We identified seven patients bearing new mutations in TGM6. To gain insights into the molecular basis of mutant TG6-induced neurotoxicity, we analyzed all of the seven new TG6 mutants and the five TG6 mutants previously linked to SCA35. We found that wild-type (TG6-WT) mainly localized to the nucleus and perinuclear area, whereas five TG6 mutations showed nuclear depletion, increased accumulation in the perinuclear area, insolubility and loss of enzymatic function. Aberrant accumulation of these TG6 mutants in the perinuclear area led to activation of the unfolded protein response (UPR), suggesting that specific TG6 mutants elicit an endoplasmic reticulum (ER) stress response. Mutations associated with activation of the UPR caused death of primary neurons and reduced the survival of novel D. melanogaster models of SCA35. These results indicate that mutations differently impacting on TG6 function cause neuronal dysfunction and death through diverse mechanisms and highlight the UPR as a potential therapeutic target for patient treatment