Sialic acid is a family of acidic monosaccharides and consists of over 30 derivatives. Two major derivatives are N-acetylneuraminic acid (NeuAc) and N-glycolylneuraminic acid (NeuGc), and the hydroxylation of CMP-NeuAc is the rate limiting reaction for the production of NeuGc. The hydroxylation was carried out by a complex formed with hydroxylase, cytochrome b5, and NADH-cytochrome b5 reductase. Mouse hydroxylase was purified from the cytosolic fraction of the liver and its cDNA was cloned. Normal human tissues do not contain NeuGc. Human hydroxylase cDNA was also cloned and the sequence revealed that human hydroxylase has 92 bp deletion. The deletion is the cause of defective expression of NeuGc in human. Chimpanzee has intact hydroxylase gene and the 92 bp deletion occurred after the divergence of human ancestor from chimpanzee ancestor. Biochemical and molecular biological studies on the biosynthesis of NeuGc and biological functions of NeuGc are reviewed.
The immune system has adopted somatic DNA alterations to overcome the limitations of the genomic information. Activation induced cytidine deaminase (AID) is an essential enzyme to regulate class switch recombination (CSR), somatic hypermutation (SHM) and gene conversion (GC) of the immunoglobulin gene. AID is known to be required for DNA cleavage of S regions in CSR and V regions in SHM. However, its molecular mechanism is a focus of extensive debate. RNA editing hypothesis postulates that AID edits yet unknown mRNA, to generate specific endonucleases for CSR and SHM. By contrast, DNA deamination hypothesis assumes that AID deaminates cytosine in DNA, followed by DNA cleavage by base excision repair enzymes. We summarize the basic knowledge for molecular mechanisms for CSR and SHM and then discuss the importance of AID not only in the immune regulation but also in the genome instability.
Pozzuoli is located at the center of the Campi Flegrei caldera, near Naples and is famous for its anomalous subsidence and upheaval documented since the Roman period. Its secular and gradual subsidence can be interpreted as self-loading compaction of the caldera fills while abrupt upheavals are geologically suspected to be caused by magmagenic movements or steam forces. In order to interpret the origin and the process of the Pozzuoli upheavals, they are compared with active volcanisms represented by the 1977-1982 eruption of Usu volcano in Hokkaido. Usu volcano outburst in 1977 in major pumice eruptions and repeated magmatic and phreatomagmatic eruptions, and manifested remarkable ground deformations accompanying earthquake swarms. In 1969, the ground of Pozzuoli began to upheave with increases in seismicity but finally failed to cause any eruptive phenomena at the surface; nevertheless there are common characteristics of their motives and processes between the two events. The motive of the Usu deformation is clearly due to magma movements while that of the Pozzuoli upheaval has not been completely settled. A quantitative relationship between seismicity and deformation gives a clue for discussing the motive of the Pozzuoli deformations. The discharge rates of seismic energy and the deformation rates are compared between the two events and a certain similarity is found. This suggests that the origin of the Pozzuoli event may be partly magmatic as well as the Usu eruption, but its behavior largely depends on the property of the caldera deposits. When their deformation volumes are taken into consideration, their characteristics become quantitatively conspicuous. The ground at Pozzuoli is much more easily deformed by the upward motive force than Usu volcano. This is due to the rheological property of the caldera deposits of Campi Flegrei, and agrees to the theory that interprets the secular subsidence observed in historical times, as self-loading compaction. It is interesting that there is a point of contact between anomalous movements of the ground along the seashore in Italy and remarkable magmatic movements at the active volcano in Japan.