Arginine mutation alters binding of a human monoclonal antibody to antigens linked to systemic lupus erythematosus and the antiphospholipid syndrome

Objective: Previous studies have shown the importance of somatic mutations and arginine residues in the complementarity-determining regions (CDRs) of pathogenic anti-double-stranded DNA (anti-dsDNA) antibodies in human and murine lupus, and in studies of murine antibodies, a role of mutations at position 53 in VH CDR2 has been demonstrated. We previously demonstrated in vitro expression and mutagenesis of the human IgG1 monoclonal antibody B3. The present study was undertaken to investigate, using this expression system, the importance of the arginine residue at position 53 (R53) in B3 VH. Methods: R53 was altered, by site-directed mutagenesis, to serine, asparagine, or lysine, to create 3 expressed variants of VH. In addition, the germline sequence of the VH3-23 gene (from which B3 VH is derived) was expressed either with or without arginine at position 53. These 5 new heavy chains, as well as wild-type B3 VH, were expressed with 4 different light chains, and the resulting antibodies were assessed for their ability to bind to nucleosomes, -actinin, cardiolipin, ovalbumin, 2-glycoprotein I (2GPI), and the N-terminal domain of 2GPI (domain I), using direct binding assays. Results: The presence of R53 was essential but not sufficient for binding to dsDNA and nucleosomes. Conversely, the presence of R53 reduced binding to -actinin, ovalbumin, 2GPI, and domain I of 2GPI. The combination B3 (R53S) VH/B3 VL bound human, but not bovine, 2GPI. Conclusion: The fact that the R53S substitution significantly alters binding of B3 to different clinically relevant antigens, but that the alteration is in opposite directions depending on the antigen, implies that this arginine residue plays a critical role in the affinity maturation of antibody B3

Assignment of the NV0 575 nm zero-phonon line in diamond to a 2E-2A2 transition

The time-averaged emission spectrum of single nitrogen-vacancy defects in diamond gives zero-phonon lines of both the negative charge state at 637 nm (1.945 eV) and the neutral charge state at 575 nm (2.156 eV). This occurs through photo-conversion between the two charge states. Due to strain in the diamond the zero-phonon lines are split and it is found that the splitting and polarization of the two zero-phonon lines are the same. From this observation and consideration of the electronic structure of the nitrogen-vacancy center it is concluded that the excited state of the neutral center has A2 orbital symmetry. The assignment of the 575 nm transition to a 2E - 2A2 transition has not been established previously.Comment: 5 pages, 5 figure

Isotope effect in quasi-two-dimensional metal-organic antiferromagnets

Although the isotope effect in superconducting materials is well-documented, changes in the magnetic properties of antiferromagnets due to isotopic substitution are seldom discussed and remain poorly understood. This is perhaps surprising given the possible link between the quasi-two-dimensional (Q2D) antiferromagnetic and superconducting phases of the layered cuprates. Here we report the experimental observation of shifts in the N\'{e}el temperature and critical magnetic fields ($\Delta T_{\rm N}/T_{\rm N}\approx 4$; $\Delta B_{\rm c}/B_{\rm c}\approx 4$) in a Q2D organic molecular antiferromagnets on substitution of hydrogen for deuterium. These compounds are characterized by strong hydrogen bonds through which the dominant superexchange is mediated. We evaluate how the in-plane and inter-plane exchange energies evolve as the hydrogens on different ligands are substituted, and suggest a possible mechanism for this effect in terms of the relative exchange efficiency of hydrogen and deuterium bonds

High titers of transmissible spongiform encephalopathy infectivity associated with extremely low levels of PrP in vivo

Rona Barron - ORCID: 0000-0003-4512-9177 https://orcid.org/0000-0003-4512-9177Diagnosis of transmissible spongiform encephalopathy (TSE) disease in humans and ruminants relies on the detection in post-mortem brain tissue of the protease-resistant form of the host glycoprotein PrP. The presence of this abnormal isoform (PrPSc) in tissues is taken as indicative of the presence of TSE infectivity. Here we demonstrate conclusively that high titers of TSE infectivity can be present in brain tissue of animals that show clinical and vacuolar signs of TSE disease but contain low or undetectable levels of PrPSc. This work questions the correlation between PrPSc level and the titer of infectivity and shows that tissues containing little or no proteinase K-resistant PrP can be infectious and harbor high titers of TSE infectivity. Reliance on protease-resistant PrPSc as a sole measure of infectivity may therefore in some instances significantly underestimate biological properties of diagnostic samples, thereby undermining efforts to contain and eradicate TSEs.https://doi.org/10.1074/jbc.M704329200282pubpub4

Photon Echoes Produced by Switching Electric Fields

We demonstrate photon echoes in Eu$^{3+}$:Y$_{2}$SiO$_{5}$ by controlling the inhomogeneous broadening of the Eu$^{3+}$ $^{7}$F$_{0}\leftrightarrow^{5}$D$_{0}$ optical transition. This transition has a linear Stark shift and we induce inhomogeneous broadening by applying an external electric field gradient. After optical excitation, reversing the polarity of the field rephases the ensemble, resulting in a photon echo. This is the first demonstration of such a photon echo and its application as a quantum memory is discussed.Comment: improved introduction, including theoretical outline of the relvant quantum memory proposa

Magnetic properties of the quasi-two-dimensional S = 1/2 Heisenberg antiferromagnet [Cu(pyz)2(HF2)]PF6

We report on high-field magnetization, specific-heat and electron spin resonance (ESR) studies of the quasi-two-dimensional spin-1/2 Heisenberg antiferromagnet [Cu(pyz)2(HF2)]PF6. The frequency-field diagram of ESR modes below TN = 4.38 K is described in the frame of the meanfield theory, confirming a collinear magnetic structure with an easy-plane anisotropy. The obtained results allowed us to determine the anisotropy/exchange interaction ratio, A/J = 0.003, and the upper limit for the inter/intra-plane exchange-interaction ratio, J'/J = 1/16. It is argued that despite the onset of 3D long-range magnetic ordering the magnetic properties of this material (including high-magnetic-field magnetization and non-monotonic field dependence of the Neel temperature) are strongly affected by two-dimensional spin correlations.Comment: 5 pages, 7 figure

Empirical wind model for the middle and lower atmosphere. Part 1: Local time average

The HWM90 thermospheric wind model was revised in the lower thermosphere and extended into the mesosphere and lower atmosphere to provide a single analytic model for calculating zonal and meridional wind profiles representative of the climatological average for various geophysical conditions. Gradient winds from CIRA-86 plus rocket soundings, incoherent scatter radar, MF radar, and meteor radar provide the data base and are supplemented by previous data driven model summaries. Low-order spherical harmonics and Fourier series are used to describe the major variations throughout the atmosphere including latitude, annual, semiannual, and longitude (stationary wave 1). The model represents a smoothed compromise between the data sources. Although agreement between various data sources is generally good, some systematic differences are noted, particularly near the mesopause. Root mean square differences between data and model are on the order of 15 m/s in the mesosphere and 10 m/s in the stratosphere for zonal wind, and 10 m/s and 4 m/s, respectively, for meridional wind