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In many vertebrate species, sex is determined at fertilization of zygotes by sex chromosome composition, knows as genotypic sex determination (GSD). But in some species-fish, amphibians and reptiles-sex is determined by environmental factors; in particular by temperature-dependent sex determination (TSD). However, little is known about the mechanisms involved in TSD and GSD. How does TSD differ from GSD? As is well known, genes that activated downstream of sex-determining genes are conserved throughout all classes of vertebrates. What is the main factor that determines sex, then? Sex steroids can reverse sex of several species of vertebrate; estrogens induce the male-to-female sex-reversal, whereas androgens do the female-to-male sex-reversal. For such sex-reversal, a functioning sex-determining gene is not required. However, in R. rugosa CYP19 (P450 aromatase) is expressed at high levels in indifferent gonads before phenotypic sex determination, and the gene is also active in the bipotential gonad of females before sex determination. Thus, we may predict that an unknown factor, a common transcription factor locates on the X and/or W chromosome, intervenes directly or indirectly in the transcriptional up-regulation of the CYP19 gene for feminization in species of vertebrates with both TSD and GSD. Similarly, an unknown factor on the Z and/or Y chromosome probably intervenes directly or indirectly in the regulation of androgen biosynthesis for masculinization. In both cases, a sex-determining gene is not always necessary for sex determination. Taken together, sex steroids may be the key-factor for sex determination in some species of vertebrates.

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Sex chromosomes of the Japanese frog Rana rugosa are heteromorphic in the male (XX/XY) or in the female (ZZ/ZW) in two geographic forms, whereas they are still homomorphic in both sexes in two other forms (Hiroshima and Isehara types). To make clear the origin and differentiation mechanisms of the heteromorphic sex chromosomes, we isolated a sex-linked gene, ADP/ATP translocase, and constructed a phylogenetic tree of the genes derived from the sex chromosomes. The tree shows that the Hiroshima gene diverges first, and the rest form two clusters: one includes the Y and Z genes and the other includes the X, W, and Isehara genes. The Hiroshima gene shares more sequence similarity with the Y and Z genes than with the X, W, and Isehara genes. This suggests that the Y and Z sex chromosomes originate from the Hiroshima type, whereas the X and W chromosomes originate from the Isehara-type sex chromosome. Thus, we infer that hybridization between two ancestral forms, with the Hiroshima-type sex chromosome in one and the Isehara-type sex chromosome in the other, was the primary event causing differentiation of the heteromorphic sex chromosomes.

Astronauts experience osteoporosis‐like loss of bone mass because of microgravity conditions during space flight. To prevent bone loss, they need a riskless and antiresorptive drug. Melatonin is reported to suppress osteoclast function. However, no studies have examined the effects of melatonin on bone metabolism under microgravity conditions. We used goldfish scales as a bone model of coexisting osteoclasts and osteoblasts and demonstrated that mRNA expression level of acetylserotonin O‐methyltransferase, an enzyme essential for melatonin synthesis, decreased significantly under microgravity. During space flight, microgravity stimulated osteoclastic activity and significantly increased gene expression for osteoclast differentiation and activation. Melatonin treatment significantly stimulated Calcitonin (an osteoclast‐inhibiting hormone) mRNA expression and decreased the mRNA expression of receptor activator of nuclear factor κB ligand (a promoter of osteoclastogenesis), which coincided with suppressed gene expression levels for osteoclast functions. This is the first study to report the inhibitory effect of melatonin on osteoclastic activation by microgravity. We also observed a novel action pathway of melatonin on osteoclasts via an increase in CALCITONIN secretion. Melatonin could be the source of a potential novel drug to prevent bone loss during space flight.

Amphibians employ genetic sex determination systems with male and female heterogamety. The ancestral state of sex determination in amphibians has been suggested to be female heterogamety; however, the origins of the sex chromosomes and the sex-determining genes are still unknown. In Xenopus laevis, chromosome 3 with a candidate for the sex- (ovary-) determining gene (DM-W) was recently identified as the W sex chromosome. This study conducted comparative genomic hybridization for X. laevis and Xenopus tropicalis and FISH mapping of eight sexual differentiation genes for X. laevis, X. tropicalis, and Rana rugosa. Three sex-linked genes of R. rugosa--AR, SF-1/Ad4BP, and Sox3--are all localized to chromosome 10 of X. tropicalis, whereas AR and SF-1/Ad4BP are mapped to chromosome 14 and Sox3 to chromosome 11 in X. laevis. These results suggest that the W sex chromosome was independently acquired in the lineage of X. laevis, and the origins of the ZW sex chromosomes are different between X. laevis and R. rugosa. Cyp17, Cyp19, Dmrt1, Sox9, and WT1 were localized to autosomes in X. laevis and R. rugosa, suggesting that these five genes probably are not candidates for the sex-determining genes in the two anuran species.

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Gelatin sponge and polyvinyl alcohol particles have been the most popular particulate embolic agents for transarterial chemoembolization (TACE) of liver tumors. Over the last decade, calibrated microspheres have been introduced and increasingly used in liver tumor embolization in Western countries. In addition, drug-eluting beads (DEB) have been introduced for sustained local drug release. Such long-awaited spherical embolic agents will be introduced in Japan in the near future. The advantages of these microspheres are that particles are uniform in size and shape, and easy to inject through a microcatheter. They can travel distally to vessels corresponding to the particle size; in other words, the occlusion level can be predicted according to the particle size chosen. Thus, new bland microspheres and DEB may bring a significant advancement to embolization for primary liver tumors as well as hepatic metastases from various cancers. However, at this point, the published data suggests that both conventional TACE and DEB-TACE are equally effective for treatment of unresectable hepatocellular carcinoma, when patients are carefully selected. Therefore, indication, patient selection, and embolization techniques will be essential in order to individually adapt newer embolic agents based on oncological, anatomical and technical considerations.