Carbamylation reduces the capacity of IgG for hexamerization and complement activation.

Carbamylation is a post-translational modification that can be detected on a range of proteins, including immunoglobulin (Ig)G, in several clinical conditions. Carbamylated IgG (ca-IgG) was reported to lose its capacity to trigger complement activation, but the mechanism remains unclear. Because C1q binds with high affinity to hexameric IgG, we analyzed whether carbamylation of IgG affects binding of C1q, hexamerization and complement-dependent cytotoxicity (CDC). Synovial tissues of rheumatoid arthritis (RA) patients were analyzed for the presence of ca-IgG in vivo. Synovial tissues from RA patients were analyzed for the presence of ca-IgG using mass spectrometry (MS). Monomeric or hexameric antibodies were carbamylated in vitro and quality in solution was controlled. The capacity of ca-IgG to activate complement was analyzed in enzyme-linked immunosorbent (ELISAs) and cellular CDC assays. Using MS, we identified ca-IgG to be present in the joints of RA patients. Using in vitro carbamylated antibodies, we observed that ca-IgG lost its capacity to activate complement in both solid-phase and CDC assays. Mixing ca-IgG with non-modified IgG did not result in effective inhibition of complement activation by ca-IgG. Carbamylation of both monomeric IgG and preformed hexameric IgG greatly impaired the capacity to trigger complement activation. Furthermore, upon carbamylation, the preformed hexameric IgG dissociated into monomeric IgG in solution, indicating that carbamylation influences both hexamerization and C1q binding. In conclusion, ca-IgG can be detected in vivo and has a strongly reduced capacity to activate complement which is, in part, mediated through a reduced ability to form hexamers.

Production of complement components by cells of the immune system.

The complement system is an important part of the innate immune defence. It contributes not only to local inflammation, removal and killing of pathogens, but it also assists in shaping of the adaptive immune response. Besides a role in inflammation, complement is also involved in physiological processes such as waste disposal and developmental programmes. The complement system comprises several soluble and membrane-bound proteins. The bulk of the soluble proteins is produced mainly by the liver. While several complement proteins are produced by a wide variety of cell types, other complement proteins are produced by only a few related cell types. As these data suggest that local production by specific cell types may have specific functions, more detailed studies have been employed recently analysing the local and even intracellular role of these complement proteins. Here we review the current knowledge about extrahepatic production and/or secretion of complement components. More specifically, we address what is known about complement synthesis by cells of the human immune system.

Phonon density of states of iron up to 153 gigapascals.

We report phonon densities of states (DOS) of iron measured by nuclear resonant inelastic x-ray scattering to 153 gigapascals and calculated from ab initio theory. Qualitatively, they are in agreement, but the theory predicts density at higher energies. From the DOS, we derive elastic and thermodynamic parameters of iron, including shear modulus, compressional and shear velocities, heat capacity, entropy, kinetic energy, zero-point energy, and Debye temperature. In comparison to the compressional and shear velocities from the preliminary reference Earth model (PREM) seismic model, our results suggest that Earth's inner core has a mean atomic number equal to or higher than pure iron, which is consistent with an iron-nickel alloy.

Genetic parameters for cystic ovarian disease in dutch black and white dairy cattle.

Cystic ovarian disease (COD) is one of the most frequently diagnosed gynecological findings in dairy cattle. It causes temporary infertility and is likely to affect reproduction as well as production parameters in cows. The objectives of this study were to investigate the heritability of COD in a Dutch Black and White population and to estimate the genetic and phenotypic relationships with milk production traits. In the data set used, the overall incidence of COD was 7.7% (1204 COD diagnoses in 15,562 lactations). The farm incidence varied between 1.9 and 11.3%. The estimated heritabilities on the underlying and observable scales were 0.102 and 0.087, respectively. The genetic correlations between COD and 305-d milk, fat, and protein yields were 0.345, 0.379, and 0.441, respectively. We concluded that a genetic predisposition for COD exists in Dutch Black and White dairy cattle. The genetic correlations between COD and yield traits indicate that ongoing selection for production will increase the incidence of COD.

Density of phonon states in iron at high pressure

The lattice dynamics of the hexagonal close-packed (hcp) phase of iron was studied with nuclear inelastic absorption of synchrotron radiation at pressures from 20 to 42 gigapascals. A variety of thermodynamic parameters were derived from the measured density of phonon states for hcp iron, such as Debye temperatures, Gruneisen parameter, mean sound velocities, and the lattice contribution to entropy and specific heat. The results are of geophysical interest, because hcp iron is considered to be a major component of Earth's inner core.