The recent finding of somatically mutated mu heavy chain transcripts in human peripheral blood (PB) B lymphocytes suggests that T-dependent B-cell memory might not be restricted to class-switched cells. We provide here evidence that IgM-only PB B cells are likely to be the IgM-expressing counterpart of classical (IgM- IgD-) memory B cells in humans. As shown by molecular single cell analysis, m...

Acetyl-CoA synthetase catalyzes the activation of acetate by the acetylation of the thiol group of Coenzyme A, while hydrolyzing ATP to AMP and pyrophosphate. The Arabidopsis thaliana acetyl-CoA synthetase (atACS) was compared to other acyl-CoA synthetases, and was computationally modeled on the available crystal structures of the Saccharomyces cerevisiae ACS1 and Salmonella enterica ACS. This ...

TLR9 activation by unmethylated CpG provides a homeostatic mechanism to maintain B cell memory in the absence of Ag. In this study, we demonstrate that CpG also triggers the generation of somatically mutated memory B cells from immature transitional B cells. In response to CpG, a fraction of transitional B cells proliferates and introduces somatic hypermutations in the H chain V regions. The no...

Intimal cushions form in the fetal ductus arteriosus by fibronectin-dependent smooth muscle cell migration which is associated with greater efficiency of fibronectin mRNA translation. We investigated whether the AU-rich element (ARE), UUAUUUAU, in the 3'-untranslated region (3'UTR) of fibronectin mRNA is involved in this mechanism by transfecting smooth muscle cells with plasmids containing the...

PURPOSE To report two novel mutation of the tumor-associated calcium signal transducer 2 (TACSTD2) gene in 3 Japanese patients with gelatinous drop-like corneal dystrophy (GDLD). METHODS Genomic DNAs were extracted from the peripheral blood of 3 Japanese families. The coding region of TACSTD2 was amplified by polymerase chain reaction (PCR) and subjected to direct sequencing analysis. Plasmid...

BACKGROUND Janus kinase-2 (JAK2) is mutated in a high proportion of patients with polycythemia vera and in a smaller number with essential thrombocythemia and primary myelofibrosis. Mutated JAK2 is an important diagnostic marker for myeloproliferative neoplasm (MPN) and may also play a major role in the pathogenesis of MPN. OBJECTIVES To evaluate the prevalence of mutated JAK2 (JAK2-V617F) am...

Therapeutic strategies for colo-rectal relies on several parameters among which microsatellite (MS) and RAS/RAF status have important value. The aim of our study was to analyze combined MS in colorectal carcinoma (CCR). We a series 73 cases CCR with nodal/visceral metastasis. determined by immunohistochemistry. Molecular testing performed the RT-PCR automatized Idylla system. 67 were MS-profici...

Gene mutations involving epigenetic regulators recently have been described in adult acute myeloid leukemia (AML). Similar studies are limited in children. We analyzed gene mutations and cooperation in pediatric AML with special reference on mutated epigenetic regulators. Nineteen gene mutations, including 8 class I genes, 4 class II genes, WT1 and TP53 (class III), and 5 epigenetic regulator g...

A single residue in the ATP binding pocket of protein kinases-termed the gatekeeper-has been shown to control sensitivity to a wide range of small molecule inhibitors (Chem. Biol.2004, 11, 691; Chem. Biol.1999, 6, 671). Kinases that possess a small side chain at this position (Thr, Ala, or Gly) are readily targeted by structurally diverse classes of inhibitors, whereas kinases that possess a la...

We have previously identified a mitochondrial DNA polymorphism (a C 3 T transition at position 3256, within the mitochondrial tRNA gene) in a patient with a multisystem disorder. Although there were several indicators suggesting a pathogenetic role for this mtDNA polymorphism, its heteroplasmic nature made functional and molecular studies difficult to interpret. We have now fused enucleated fib...