Conformational epitopes of myelin oligodendrocyte glycoprotein are targets of potentially pathogenic antibody responses in multiple sclerosis

<p>Abstract</p> <p>Background</p> <p>Myelin/oligodendrocyte glycoprotein (MOG) is a putative autoantigen in multiple sclerosis (MS). Establishing the pathological relevance and validity of anti-MOG antibodies as biomarkers has yielded conflicting reports mainly due to different MOG isoforms used in different studies. Because epitope specificity may be a key factor determining anti-MOG reactivity we aimed at identifying <it>a priori </it>immunodominant MOG epitopes by monoclonal antibodies (mAbs) and at assessing clinical relevance of these epitopes in MS.</p> <p>Methods</p> <p>Sera of 325 MS patients, 69 patients with clinically isolated syndrome and 164 healthy controls were assayed by quantitative, high-throughput ELISA for reactivity to 3 different MOG isoforms, and quantitative titers correlated with clinical characteristics. mAbs defined unique immunodominant epitopes distinct to each of the isoforms.</p> <p>Results</p> <p>In the majority of human samples anti-MOG levels were skewed towards low titers. However, in 8.2% of samples high-titer anti-MOG antibodies were identified. In contrast to anti-MOG reactivity observed in a mouse model of MS, in patients with MS these never reacted with ubiquitously exposed epitopes. Moreover, in patients with relapsing-remitting MS high-titer anti-MOG IgG correlated with disability (EDSS; Spearman r = 0.574; p = 0.025).</p> <p>Conclusions</p> <p>Thus high-titer reactivity likely represents high-affinity antibodies against pathologically relevant MOG epitopes, that are only present in a small proportion of patients with MS. Our study provides valuable information about requirements of anti-MOG reactivity for being regarded as a prognostic biomarker in a subtype of MS.</p

Detection of sperm antigens on mouse ova and early embryos

Serum and colostrum antibodies against mouse sperm were developed in two rabbits after systemic and mammary gland immunizations. Indirect immunofluorescence utilizing fluorescein-labeled goat antisera against rabbit IgG and IgA, respectively, indicated that both immune serum (IS) and colostrum (IC) compared with control samples caused intensive staining of the acrosome and tail of sperm. Absorption of IS and IC with mouse serum and the spleen, kidney, liver, and brain of male mice did not reduce the strength or the pattern of staining reaction on sperm. The absorbed IS reacted with cell surfaces of oocytes, unfertilized ova, zygotes, two-cell and four- to eight-cell fertilized ova, and blastocysts. The absorbed IC, however, reacted only with the four- to eight-cell embryo and blastocyst. Further absorption of the IS with mouse ovary removed the reaction with unfertilized ova and the one- to two-cell fertilized ova, but the staining of later embryo stages was unaffected. Therefore, it appears that specific rabbit anti-sperm antibodies are detecting two cell-membrane antigens on mouse embryos: one originating from the ovary and the other arising after fertilization.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/22638/1/0000189.pd

Exact Critical Exponents for Pseudo-Particles in the Kondo Problem

Exact critical exponents of the Green functions for pseudo-fermions and slave bosons in the SU($N$) Anderson model with $U\rightarrow\infty$ are obtained by using the Bethe ansatz solution and boundary conformal field theory. They are evaluated exactly for mixed valence systems and Kondo systems with crystalline fields. The results agree with the prediction of Menge and M\"uller-Hartmann, which coincide with those of the X-ray problem. Some implication of our results in one-dimensional chiral systems is also discussed.Comment: 9 pages, no figure

Evidence for Contemporary Switching of the O-Antigen Gene Cluster between Shiga Toxin-Producing Escherichia coli Strains Colonizing Cattle

Shiga toxin-producing Escherichia coli (STEC) comprise a group of zoonotic enteric pathogens with ruminants, especially cattle, as the main reservoir. O-antigens are instrumental for host colonization and bacterial niche adaptation. They are highly immunogenic and, therefore, targeted by the adaptive immune system. The O-antigen is one of the most diverse bacterial cell constituents and variation not only exists between different bacterial species, but also between individual isolates/strains within a single species. We recently identified STEC persistently infecting cattle and belonging to the different serotypes O156:H25 (n = 21) and O182:H25 (n = 15) that were of the MLST sequence types ST300 or ST688. These STs differ by a single nucleotide in purA only. Fitness-, virulence-associated genome regions, and CRISPR/CAS (clustered regularly interspaced short palindromic repeats/CRISPR associated sequence) arrays of these STEC O156:H25 and O182:H25 isolates were highly similar, and identical genomic integration sites for the stx converting bacteriophages and the core LEE, identical Shiga toxin converting bacteriophage genes for stx1a, identical complete LEE loci, and identical sets of chemotaxis and flagellar genes were identified. In contrast to this genomic similarity, the nucleotide sequences of the O-antigen gene cluster (O-AGC) regions between galF and gnd and very few flanking genes differed fundamentally and were specific for the respective serotype. Sporadic aEPEC O156:H8 isolates (n = 5) were isolated in temporal and spatial proximity. While the O-AGC and the corresponding 5′ and 3′ flanking regions of these aEPEC isolates were identical to the respective region in the STEC O156:H25 isolates, the core genome, the virulence associated genome regions and the CRISPR/CAS elements differed profoundly. Our cumulative epidemiological and molecular data suggests a recent switch of the O-AGC between isolates with O156:H8 strains having served as DNA donors. Such O-antigen switches can affect the evaluation of a strain's pathogenic and virulence potential, suggesting that NGS methods might lead to a more reliable risk assessment

Conductivity in a symmetry broken phase: Spinless fermions with 1/d1/d corrections

The dynamic conductivity $\sigma(\omega)$ of strongly correlated electrons in a symmetry broken phase is investigated in the present work. The model considered consists of spinless fermions with repulsive interaction on a simple cubic lattice. The investigated symmetry broken phase is the charge density wave (CDW) with wave vector $Q=(\pi,\pi,\pi)^\dagger$ which occurs at half-filling. The calculations are based on the high dimensional approach, i.e. an expansion in the inverse dimension $1/d$ is used. The finite dimensionality is accounted for by the inclusion of linear terms in $1/d$ and the true finite dimensional DOS. Special care is paid to the setup of a conserving approximation in the sense of Baym/Kadanoff without inconsistencies. The resulting Bethe-Salpeter equation is solved for the dynamic conductivity in the non symmetry broken and in the symmetry broken phase (AB-CDW). The dc-conductivity is reduced drastically in the CDW. Yet it does not vanish in the limit $T \to 0$ due to a subtle cancellation of diverging mobility and vanishing DOS. In the dynamic conductivity $\sigma(\omega)$ the energy gap induced by the symmetry breaking is clearly discernible. In addition, the vertex corrections of order $1/d$ lead to an excitonic resonance lying within the gap.Comment: 23 pages, 19 figures included with psfig, Revtex; Physical Review B15, in press (October/November 1996) depending on the printer/screen driver, it might be necessary to comment out figures 3,4,5,10,11,12,19 and have them printed separatel

Dynamical correlations in multiorbital Hubbard models: Fluctuation-exchange approximations

We study the two band degenerate Hubbard model using the Fluctuation Exchange approximation (FLEX) method and compare the results with Quantum Monte-Carlo calculations. Both the self-consistent and the non-self-consistent versions of the FLEX scheme are investigated. We find that, contrary to the one band case, in the multiband case, good agreement with the Quantum Monte-Carlo results is obtained within the electron-electron T-matrix approximation using the full renormalization of the one-particle propagators. The crossover to strong coupling and the formation of satellites is more clearly visible in the non-self-consistent scheme. Finally we discuss the behavior of the FLEX for higher orbital degeneracy.Comment: 18 pages with 12 PS figure

Characterization of the binding site of the histamine H3 receptor. 1. Various approaches to the synthesis of 2-(1H-imidazol-4-yl)cyclopropylamine and histaminergic activity of (1R,2R)-and (1S,2S)-2-(1H-imidazol-4-yl)-cyclopropylamine.

Various approaches to the synthesis of all four stereoisomers of 2-(1H- imidazol-4-yl)cyclopropylamine (cyclopropylhistamine) are described. The rapid and convenient synthesis and resolution of trans-cyclopropylhistamine is reported. The absolute configuration of its enantiomers was determined by single-crystal X-ray crystallographic analysis. The distinct transcyclopropylhistamine enantiomers were tested for their activity and affinity on the histamine

Unified description of Fermi and non-Fermi liquid behavior in a conserving slave boson approximation for strongly correlated impurity models

We show that the presence of Fermi or non-Fermi liquid behavior in the SU(N) x SU(M) Anderson impurity models may be read off the infrared threshold exponents governing the spinon and holon dynamics in a slave boson representation of these models. We construct a conserving T-matrix approximation which recovers the exact exponents with good numerical accuracy. Our approximation includes both coherent spin flip scattering and charge fluctuation processes. For the single-channel case the tendency to form bound states drastically modifies the low energy behavior. For the multi-channel case in the Kondo limit the bound state contributions are unimportant.Comment: 4 pages, Latex, 3 postscript figures included Final version with minor changes in wording, to appear in Phys.Rev.Let