Expression analysis of a mouse orthologue of HSFY, a candidate for the azoospermic factor on the human Y chromosome

Heat shock transcription factor on Y (HSFY) is located in one of three candidate regions for azoospermic factor (AZF), AZFb on the Y chromosome. We and others have already revealed that some azoospermic males are missing the regions of the Y chromosome including HSFY. Previously, we showed that murine HSFY-like sequence〔mHSFYL(RikencDNA4933413G11Rik)〕, which is the mouse orthologue of HSFY, is exclusively expressed in testis. The sequences encoding the presumed DNA-binding domain in HSFY and mHSFYL were found in other mammals such as dogs, cows and chickens. To elucidate mHSFYL expression in the testes in detail, we carried out in situ hybridization. mHSFYL was predominantly expressed in round spermatids. Furthermore, we clarified the intracellular distribution of mHSFYL inCOS1 cells with HA- or GFP-tagged proteins. Both HA-mHSFYL and GFP-mHSFYL were located in the nucleus. Our results suggest that HSFY/mHSFYL may have evolutionarily conserved functions for spermatogenesis

Applicability of source scaling relations for crustal earthquakes to estimation of the ground motions of the 2016 Kumamoto earthquake

A two-stage scaling relationship of the source parameters for crustal earthquakes in Japan has previously been constructed, in which source parameters obtained from the results of waveform inversion of strong motion data are combined with parameters estimated based on geological and geomorphological surveys. A three-stage scaling relationship was subsequently developed to extend scaling to crustal earthquakes with magnitudes greater than M w 7.4. The effectiveness of these scaling relationships was then examined based on the results of waveform inversion of 18 recent crustal earthquakes (M w 5.4–6.9) that occurred in Japan since the 1995 Hyogo-ken Nanbu earthquake. The 2016 Kumamoto earthquake, with M w 7.0, was one of the largest earthquakes to occur since dense and accurate strong motion observation networks, such as K-NET and KiK-net, were deployed after the 1995 Hyogo-ken Nanbu earthquake. We examined the applicability of the scaling relationships of the source parameters of crustal earthquakes in Japan to the 2016 Kumamoto earthquake. The rupture area and asperity area were determined based on slip distributions obtained from waveform inversion of the 2016 Kumamoto earthquake observations. We found that the relationship between the rupture area and the seismic moment for the 2016 Kumamoto earthquake follows the second-stage scaling within one standard deviation (σ = 0.14). The ratio of the asperity area to the rupture area for the 2016 Kumamoto earthquake is nearly the same as ratios previously obtained for crustal earthquakes. Furthermore, we simulated the ground motions of this earthquake using a characterized source model consisting of strong motion generation areas (SMGAs) based on the empirical Green’s function (EGF) method. The locations and areas of the SMGAs were determined through comparison between the synthetic ground motions and observed motions. The sizes of the SMGAs were nearly coincident with the asperities with large slip. The synthetic ground motions obtained using the EGF method agree well with the observed motions in terms of acceleration, velocity, and displacement within the frequency range of 0.3–10 Hz. These findings indicate that the 2016 Kumamoto earthquake is a standard event that follows the scaling relationship of crustal earthquakes in Japan

Genetic Polymorphisms of 17β-Hydroxysteroid Dehydrogenase 3 and the Risk of Hypospadias

Introduction: Hypospadias is a common congenital anomaly caused by incomplete fusion of urethral folds. Development of the urethra and external genital system in the male fetus is an androgen-dependent process. In this regard, enzymes 17β-hydroxysteroid dehydrogenase type 3 (17βHSD3, encoded by HSD17B3) and steroid 5α-reductase type 2 (encoded by SRD5A2) play crucial roles. Aim; To investigate the possible associations between common polymorphisms in HSD17B3 as well as well-known V89L polymorphism in SRD5A2 and risk of hypospadias. Methods: A case-control study was performed between 1999 and 2005. There were 89 Japanese boys with hypospadias and 291 newborn controls. We genotyped HSD17B3−1999T>C, +10A>G, +20A>G, +139G>A (V31I), +913G>A (G289S), and SRD5A2+336G>C (V89L) polymorphisms by allelic discrimination assay. We measured mRNA expression of the wildtype G289 allele and the mutant S289 allele of the HSD17B3 gene in the transfected human fetal kidney HEK293 cells. Main Outcome Measures: Assessment of hypospadias including its severity and HSD17B3 and SRD5A2 genes using DNA blood samples: allele and genotype distribution of single nucleotide polymorphisms in these two genes in cases and controls. Results: In our study, the risk of hypospadias was significantly higher in subjects carrying homozygous HSD17B3+913A (289S) alleles (odds ratio [OR]: 3.06; 95% confidence interval [CI]: 1.38–6.76). The risk of severe hypospadias was much higher in these subjects (OR: 3.93; 95% CI: 1.34–11.49). The mRNA expression levels of HSD17B3 G289 were higher than those of HSD17B3 S289 mutant (P < 0.001). In addition, the risk of severe hypospadias increased in boys carrying the SRD5A2+336C (89L) allele (OR: 3.19; 95% CI: 1.09–9.36). Conclusions: These results suggest that the HSD17B3 G289S polymorphism may be a potential risk modifier for hypospadias. Our findings provide evidence that a certain genotype related to androgen production may potentiate risk of hypospadias. Sata F, Kurahashi N, Ban S, Moriya K, Tanaka KD, Ishizuka M, Nakao H, Yahata Y, Imai H, Kakizaki H, Nonomura K, and Kishi R. Genetic polymorphisms of 17β-hydroxysteroid dehydrogenase 3 and the risk of hypospadias