Although 12 of 58 patients (21%) had an infection, pretransplantation immunization was effective to prevent serious illness, especially for the 6 months after transplantation. Posttransplantation live-vaccine administration under immunosuppressive conditions is effective and safe.

ICF syndrome is a rare autosomal recessive disorder characterized by immunodeficiency, centromeric instability, and facial anomalies. It is caused by mutations in a de novo DNA methyltransferase gene, DNMT3B. We here report the first three Japanese cases of ICF syndrome from two unrelated families. All patients had typical facial dysmorphism and immunoglobulin A (IgA) deficiency, but none of them had apparent mental retardation. Cytogenetic analysis of peripheral blood lymphocytes showed chromosomal abnormalities, including multiradial configurations and a stretching of the pericentromeric heterochromatin of chromosomes 1 and 16. Hypomethylation of classical satellite 2 DNA was also observed. Mutation analyses of DNMT3B revealed three novel mutations: patient 1 from the first family was a compound heterozygote for a nonsense mutation (Q42Term) and a missense mutation (R832Q); patients 2 and 3 from the second family were both homozygous for a missense mutation (S282P). The R832Q mutation occurred within the conserved methyltransferase domain, and thus may affect the enzyme activity directly. The S282P mutation, on the other hand, occurred close to the PWWP domain, which is presumably involved in protein-protein interaction. This is the first missense mutation mapped to the N-terminal half of the protein, suggesting that the region plays an important role in the regulation of the DNMT3B enzyme.

We focus on the evidence of a past minor merger discovered in the halo of the Andromeda galaxy (M31). Previous N-body studies have enjoyed moderate success in producing the observed giant stellar stream (GSS) and stellar shells in M31's halo. The observed distribution of stars in the halo of M31 shows an asymmetric surface brightness profile across the GSS; however, the effect of the morphology of the progenitor galaxy on the internal structure of the GSS requires further investigation in theoretical studies. To investigate the physical connection between the characteristic surface brightness in the GSS and the morphology of the progenitor dwarf galaxy, we systematically vary the thickness, rotation velocity and initial inclination of the disc dwarf galaxy in N-body simulations. The formation of the observed structures appears to be dominated by the progenitor's rotation. Besides reproducing the observed GSS and two shells in detail, we predict additional structures for further observations. We predict the detectability of the progenitor's stellar core in the phase-space density distribution, azimuthal metallicity gradient of the western shell-like structure and an additional extended shell in the north-western direction that may constrain the properties of the progenitor galaxy.

Mutations in the hepatocyte nuclear factor (HNF)-1 beta lead to type 5 maturity-onset diabetes of the young (MODY5). HNF-1 beta forms a homodimer or a heterodimer with HNF-1 alpha and regulates various target genes. HNF-1 beta mutations are rare, and no functional analysis has been performed in conjunction with HNF-1 alpha. HNF-1 beta is expressed in the liver and biliary system and controls liver-specific and bile acid-related genes. Moreover, liver-specific Hnf-1 beta knockout mice present with severe jaundice. However, no patients with HNF-1 beta mutations have biliary manifestations. In this report, we found a novel missense mutation in the HNF-1 beta gene in a patient with neonatal cholestasis and liver dysfunction together with the common features of MODY5. Functional analysis revealed that the mutant HNF-1 beta had diminished transcriptional activity by loss of the DNA binding activity. The mutant had a promoter-specific dominant-negative transcriptional effect on wild-type HNF- and inhibited its DNA binding. Moreover, the mutant had a promoter- and cell-specific transcriptional repressive effect on HNF-1 alpha and a promoter-specific inhibitory effect on HNF-1 alpha DNA binding. From these results, we considered that the different phenotype of patients with HNF-1 beta mutations might be caused by the different HNF-1 beta activity in conjunction with the different repression of HNF-1 alpha activity in selected promoters and tissues.

To unveil a progenitor of the Andromeda Giant Stellar Stream, we investigate the interaction between an accreting satellite galaxy and the Andromeda Galaxy using an N-body simulation. We perform a comprehensive exploration of the properties of the progenitor dwarf galaxy, using 247 models of varying mass, mass distribution, and size. We show that the binding energy of the progenitor is the crucial parameter in reproducing the Andromeda Giant Stellar Stream and the shell-like structures surrounding the Andromeda Galaxy. As a result of the simulations, the progenitor must satisfy a simple scaling relation between the core radius, the total mass and the tidal radius. Using this relation, we successfully constrain the physical properties of the progenitors to have masses ranging froḿ . A detailed comparison between our result and the nearby observed galaxies indicates that possible progenitors of the Andromeda Giant Stellar Stream include a dwarf elliptical galaxy, a dwarf irregular galaxy, and a small spiral galaxy.