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

TG6 auto-antibodies in dermatitis herpetiformis

Dermatitis herpetiformis (DH) is an extraintestinal manifestation of gluten sensitivity, in which an autoimmune response is directed against transglutaminase 3 (TG3), an epidermal transglutaminase. TG2 is the autoantigen in celiac disease (CD), defined by the presence of enteropathy, and TG6 is the autoantigen in neurological manifestations of gluten sensitivity. The interplay between B cell responses to these 3 transglutaminases in developing the clinical spectrum of disease manifestations is not completely understood. Also, the individual or combined diagnostic and predictive value of the respective autoantibodies is not fully explored. We examined the prevalence of TG6 antibodies in a cohort of patients with DH. TG6 positivity was found in 13/33 (39%), with IgA detected in 11 patients, IgG in 3, and both in 1. This was significantly higher compared to what is seen in the classic CD cases (14%) in a Finnish population. TG6 positive baseline samples constituted 60% of DH patients with no enteropathy (n = 10), as opposed to 17% positivity in those with overt enteropathy (n = 12; Marsh IIIB). Repeat testing after adherence to a gluten-free diet for 1 year showed reduced titers for TG6 antibodies in 11/13 (85%), whereby 7 patients were now TG6 antibody-negative. Four patients seroconverted and tested positive for TG6 antibodies at one year, due to the ongoing exposure to gluten. We report another patient who presented with neurological manifestations (encephalopathy) leading to the diagnosis of CD, who was intermittently adhering to a gluten-free diet. Serological testing at baseline showed him to be positive for antibodies to all 3 transglutaminases. Eleven years later, he developed DH. He also subsequently developed ataxia and peripheral neuropathy. Although TG3 and TG6 autoantibodies are linked to certain disease manifestations, TG2, TG3, and TG6 autoantibodies can be present across the spectrum of GRD patients and might develop years before onset of symptoms of extraintestinal manifestations. This is consistent with gluten-dependent adaptive immunity being a necessary but not sufficient pretext to organ-specific damage. TG6 antibodies appear to develop more frequently in patients where tolerance to gluten was broken but, either there was no development of the molecular state driving the tissue destruction at the level of the gut, or perhaps more likely, there was more resistance to developing this phenotype

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

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

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

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

Neurologic deficits in patients with newly diagnosed celiac disease are frequent and linked with autoimmunity to TG6

Background & Aims Celiac disease is an autoimmune disorder induced by ingestion of gluten that affects 1% of the population and is characterized by gastrointestinal symptoms, weight loss, and anemia. We evaluated the presence of neurologic deficits and investigated whether the presence of antibodies to TG6 increases the risk of neurologic defects in patients with a new diagnosis of celiac disease. Methods We performed a prospective cohort study at a secondary-care gastroenterology center of 100 consecutive patients who received a new diagnosis of celiac disease based on gastroscopy and duodenal biopsy. We collected data on neurologic history, and patients were evaluated in a clinical examination along with magnetic resonance imaging (MRI) of the brain, MR spectroscopy of the cerebellum, and measurements of antibodies against TG6 in serum samples. The first 52 patients recruited underwent repeat MR spectroscopy at 1 year after a gluten-free diet (GFD). The primary aim was to establish if detection of antibodies against TG6 can be used to identify patients with celiac disease and neurologic dysfunction. Results Gait instability was reported in 24% of the patients, persisting sensory symptoms in 12%, and frequent headaches in 42%. Gait ataxia was found in 29% of patients, nystagmus in 11%, and distal sensory loss in 10%. Sixty percent of patients had abnormal results from the MRI, 47% had abnormal results from MR spectroscopy of the cerebellum, and 25% had brain white matter lesions beyond that expected for their age group. Antibodies against TG6 were detected in serum samples from 40% of patients–these patients had significant atrophy of subcortical brain regions compared to patients without TG6 autoantibodies. In patients with abnormal results from MR spectroscopy of the cerebellum, those on the GFD had improvements detected in the repeat MR spectroscopy 1 year later. Conclusions In a prospective cohort study of patients with a new diagnosis of celiac disease at a gastroenterology clinic, neurological deficits were common and 40% had circulating antibodies against TG6. We observed a significant reduction in volume of specific brain regions in patients with TG6 autoantibodies, providing evidence for a link between autoimmunity to TG6 and brain atrophy in patients with celiac disease. There is a need for early diagnosis, increased awareness of the neurological manifestations amongst clinicians and reinforcement of adherence to a strict GFD by patients in order to avoid permanent neurological disability

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

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