For the identification of susceptibility loci for primary biliary cirrhosis (PBC), a genome-wide association study (GWAS) was performed in 963 Japanese individuals (487 PBC cases and 476 healthy controls) and in a subsequent replication study that included 1,402 other Japanese individuals (787 cases and 615 controls). In addition to the most significant susceptibility region, human leukocyte antigen (HLA), we identified two significant susceptibility loci, TNFSF15 (rs4979462) and POU2AF1 (rs4938534) (combined odds ratio [OR] = 1.56, p = 2.84 × 10(-14) for rs4979462, and combined OR = 1.39, p = 2.38 × 10(-8) for rs4938534). Among 21 non-HLA susceptibility loci for PBC identified in GWASs of individuals of European descent, three loci (IL7R, IKZF3, and CD80) showed significant associations (combined p = 3.66 × 10(-8), 3.66 × 10(-9), and 3.04 × 10(-9), respectively) and STAT4 and NFKB1 loci showed suggestive association with PBC (combined p = 1.11 × 10(-6) and 1.42 × 10(-7), respectively) in the Japanese population. These observations indicated the existence of ethnic differences in genetic susceptibility loci to PBC and the importance of TNF signaling and B cell differentiation for the development of PBC in individuals of European descent and Japanese individuals.

Samples of the carbonaceous asteroid Ryugu were brought to Earth by the Hayabusa2 spacecraft. We analyzed seventeen Ryugu samples measuring 1-8 mm. CO 2 -bearing water inclusions are present within a pyrrhotite crystal, indicating that Ryugu’s parent asteroid formed in the outer Solar System. The samples contain low abundances of materials that formed at high temperatures, such as chondrules and Ca, Al-rich inclusions. The samples are rich in phyllosilicates and carbonates, which formed by aqueous alteration reactions at low temperature, high pH, and water/rock ratios < 1 (by mass). Less altered fragments contain olivine, pyroxene, amorphous silicates, calcite, and phosphide. Numerical simulations, based on the mineralogical and physical properties of the samples, indicate Ryugu’s parent body formed ~ 2 million years after the beginning of Solar System formation.

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. Indeed, PDGF-B or PDGFR␤-null mice exhibit severe defects in both VSMC/pericyte number and function during late embryogenesis that combine to result in the generation of unstable blood vessels, edema, and lethal hemorrhage (Leveen et al. 1994;Soriano 1994;Lindahl et al. 1997;Hellström et al. 1999Hellström et al. , 2001. While mice harboring hypomorphic PDGF-B or PDGFR␤ alleles can survive into adulthood, mural cell number and function are nonetheless affected, resulting in an increasingly compromised vascular compartment (Tallquist et al. 2000(Tallquist et al. , 2003Enge et al. 2002;Lindblom et al. 2003; Bjanegård et al. 2004).To date, the mechanisms by which the PDGF-B/ PDGFR␤-initiated signal transduction cascade regulates mural cell function remain the subject of intense scrutiny. Following receptor ligation by PDGF-B, the PDGFR␤ dimerizes, undergoes autophosphorylation, and recruits a diverse set of at least 10 SH2 domaincontaining proteins that then activate multiple downstream cascades which serve to control migration and proliferation (DeMali et al. 1999;Hoch and Soriano 2003;Tallquist and Kazlauskas 2004). Independent of the specific roles that each of these downstream signal transduction cascades play in defining mural cell phenotype, PDGF-B/PDGFR␤ effector function can be further modulated by interactions with accessory factors ranging from non-PDGF peptide growth factors and sphingolipids to Cold Spring Harbor Laboratory Press on May 11, 2018 -Published by genesdev.cshlp.org Downloaded from