The response of Acropora digitifera to ocean acidification is determined using geochemical proxy measurements of the skeletal composition of A. digitifera cultured under a range of pH levels. We show that the chemical composition (d 11 B, Sr/Ca, Mg/Ca, and Ba/Ca) of the coral skeletons can provide quantitative constraints on the effects of seawater pH on the pH in the calcification fluid (pH CF ) and the mechanisms controlling the incorporation of trace elements into coral aragonite. With the decline of seawater pH, the skeletal d 11 B value decreased, while the Sr/Ca ratio showed an increasing trend. The relationship between Mg/Ca and Ba/Ca versus seawater pH was not significant. Inter-colony variation of d 11 B was insignificant, although inter-colony variation was observed for Ba/Ca. The decreasing trend of pH CF calculated from d 11 B was from *8.5, 8.4, and 8.3 for seawater pH of *8.1, 7.8, and 7.4, respectively. Model calculations based on Sr/Ca and pH CF suggest that upregulation of pH CF occurs via exchange of H ? with Ca 2? with kinetic effects (Rayleigh fractionation), reducing Sr/Ca relative to inorganic deposition of aragonite from seawater. We show that it is possible to constrain the overall carbonate chemistry of the calcifying fluid with estimates of the carbonate saturation of the calcifying fluid (X CF ) being derived from skeletal Sr/Ca and pH CF (from d 11 B). These estimates suggest that the aragonite saturation state of the calcifying fluid X CF is elevated by a factor of 5-10 relative to ambient seawater under all treatment conditions.

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28HLA-G is involved in maternal-fetal immune tolerance and is reported to be a natural 29 tolerogenic molecule. Seven-spliced isoforms including dimeric and β2m-free forms 30 have been identified. The major isoform, HLA-G1 (and its soluble type HLA-G5), binds

HLA-G is a natural tolerogenic molecule and has the following unique features: seven isoforms (HLA-G1 to HLA-G7), formation of disulfide-linked homodimers, and β2-microglobulin (β2m)-free forms. Interestingly, individuals null for the major isoform, HLA-G1, are healthy and expressed the α2 domain-deleted isoform, HLA-G2, which presumably compensates for HLA-G1 function. However, the molecular characteristics of HLA-G2 are largely unknown. In this study, we unexpectedly found that HLA-G2 naturally forms a β2m-free and nondisulfide-linked homodimer, which is in contrast to the disulfide-bonded β2m-associated HLA-G1 homodimer. Furthermore, single-particle analysis, using electron microscopy, revealed that the overall structure and domain organization of the HLA-G2 homodimer resemble those of the HLA class II heterodimer. The HLA-G2 homodimer binds to leukocyte Ig-like receptor B2 with slow dissociation and a significant avidity effect. These findings provide novel insights into leukocyte Ig-like receptor B2-mediated immune regulation by the HLA-G2 isoform, as well as the gene evolution of HLA classes.

-The basal transcriptional activity of unliganded human constitutive androstane receptor (hCAR) was shown to be repressed by the potent liver X receptor (LXR) agonist, T0901317, in a concentration-dependent manner using a reporter assay in cultured cells. T0901317 also repressed the basal transcriptional activity of both mouse and rat CAR. The certified hCAR agonist, CITCO, partially reversed this repressive effect of T0901317 on hCAR basal activity. Unlike hCAR, a three alanine insertion mutant and the splice variant 2 of hCAR require agonists, such as CITCO, to become transcriptionally active and the CITCO-induced reporter activity was repressed by T0901317. As has been previously shown for the typical hCAR inverse agonist, PK11195, T0901317 blocked the interaction of hCAR with steroid receptor co-activator 1 (SRC1). In contrast, the interaction between hCAR and nuclear receptor corepressor 1 (NCoR1) was promoted by PK11195 and T0901317. Furthermore, the hCAR-mediated basal induction of endogenous cytochrome P450 2B6 (CYP2B6) mRNA was adversely affected by co-treatment with T0901317.

The human leucocyte antigen (HLA)-G, which consists of seven splice variants, is a tolerogenic immune checkpoint molecule. It plays an important role in the protection of the fetus from the maternal immune response by binding to inhibitory receptors, including leukocyte Ig-like receptors (LILRs). Recent studies have also revealed that HLA-G is involved in the progression of cancer cells and the protection from autoimmune diseases. In contrast to its well characterized isoform, HLA-G1, the binding activities of other major HLA-G isoforms, such as HLA-G2, toward available anti-HLA-G antibodies are only partially understood. Here, we investigate the binding specificities of anti-HLA-G antibodies by using surface plasmon resonance. MEM-G9 and G233 showed strong affinities to HLA-G1, with a nM range for their dissociation constants, but did not show affinities to HLA-G2. The disulfide-linker HLA-G1 dimer further exhibited significant avidity effects. On the other hand, 4H84 and MEM-G1, which can be used for the Western blotting of HLA-G isoforms, can bind to native HLA-G2, while MEM-G9 and G233 cannot. These results reveal that HLA-G2 has a partially intrinsically disordered structure. Furthermore, MEM-G1, but not 4H84, competes with the LILRB2 binding of HLA-G2. These results provide novel insight into the functional characterization of HLA-G isoforms and their detection systems.

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