Search

Epidemiological studies have demonstrated that the genetic factors partly influence the development of same-sex sexual behavior, but most genetic studies have focused on people of primarily European ancestry, potentially missing important biological insights. Here, we performed a two-stage genome-wide association study (GWAS) with a total sample of 1478 homosexual males and 3313 heterosexual males in Han Chinese populations and identified two genetic loci (rs17320865, Xq27.3, FMR1NB, P

Epidemiological studies have demonstrated that the genetic factors partly influence the development of same-sex sexual behavior, but most genetic studies have focused on people of primarily European ancestry, potentially missing important biological insights. Here, we performed a two-stage genome-wide association study (GWAS) with a total sample of 1478 homosexual males and 3313 heterosexual males in Han Chinese populations and identified two genetic loci (rs17320865, Xq27.3, FMR1NB, Pmeta = 8.36 × 10−8, OR = 1.29; rs7259428, 19q12, ZNF536, Pmeta = 7.58 × 10−8, OR = 0.75) showing consistent association with male sexual orientation. A fixed-effect meta-analysis including individuals of Han Chinese (n = 4791) and European ancestries (n = 408,995) revealed 3 genome-wide significant loci of same-sex sexual behavior (rs9677294, 2p22.1, SLC8A1, Pmeta = 1.95 × 10−8; rs2414487, 15q21.3, LOC145783, Pmeta = 4.53 × 10−9; rs2106525, 7q31.1, MDFIC, Pmeta = 6.24 × 10−9). These findings may provide new insights into the genetic basis of male sexual orientation from a wider population scope. Furthermore, we defined the average ZNF536-immunoreactivity (ZNF536-ir) concentration in the suprachiasmatic nucleus (SCN) as lower in homosexual individuals than in heterosexual individuals (0.011 ± 0.001 vs 0.021 ± 0.004, P = 0.013) in a postmortem study. In addition, compared with heterosexuals, the percentage of ZNF536 stained area in the SCN was also smaller in the homosexuals (0.075 ± 0.040 vs 0.137 ± 0.103, P = 0.043). More homosexual preference was observed in FMR1NB-knockout mice and we also found significant differences in the expression of serotonin, dopamine, and inflammation pathways that were reported to be related to sexual orientation when comparing CRISPR-mediated FMR1NB knockout mice to matched wild-type target C57 male mice.

Protostane triterpenes in Alisma orientale (Sam.) Juz., because of their unique structural feature, exhibit distinctive pharmacological activities. However, the biosynthetic pathways for these compounds remain largely unknown. In this study, transcriptome analysis was performed using A. orientale tubers and leaves. We identified 101,107 unigenes, which were annotated against various databases. Importantly, 35 unigenes associated with the terpene biosynthesis pathway were identified, among which 18 encoded key enzymes catalyzing every reaction in the biosynthesis of protostane triterpenes skeleton. In addition, eight candidate transcription factor unigenes and nine candidate cytochrome P450 unigenes related to the terpene biosynthesis pathway were obtained. Moreover, the expression levels of most genes involved in protostane triterpenes biosynthesis in tubers were significantly higher than those in leaves. Furthermore, significant positive correlations were showed between the levels of key enzymes (HMGR2, SS2, SE1, SE2, OSC1, and OSC2), and the contents of the main bioactive compound at different developmental phases of A. orientale. These genes were identified first time in this study. These results provide preliminary evidence that these proteins may play crucially regulatory roles in protostane triterpenes synthesis.

The mouse interleukin-3 (IL-3)-dependent hemopoietic precursor cell line 32DC13 responds to granulocyte colony-stimulating factor (G-CSF) for proliferation and differentiation. We established a subline (32D-FH) of the 32DC13 cells which has lost the ability to respond to G-CSF. When murine G-CSF receptor cDNA was introduced into the 32D-FH cell line, the transformants responded to G-CSF as well as to IL-3 for proliferation. Adding G-CSF to the transformants rapidly induced tyrosine phosphorylation not only of the G-CSF receptor but also of both subtypes of the IL-3 receptor beta-chain (AIC2A and AIC2B molecules). On the other hand, stimulation of the transformants with IL-3 induced tyrosine phosphorylation of the AIC2A and AIC2B but not of the G-CSF receptor. These results indicate that the tyrosine kinase activated through the G-CSF receptor interacts with the IL-3 receptor beta-chains but not vice versa. This unidirectional cross-phosphorylation between the G-CSF and IL-3 receptors may play a role in granulopoiesis induced by G-CSF.

The granulocyte colony-stimulating factor (G-CSF) receptor has a composite structure consisting of an immunoglobulin(Ig)-like domain, a cytokine receptor-homologous (CRH) domain and three fibronectin type III (FNIII) domains in the extracellular region. Introduction of G-CSF receptor cDNA into IL-3-dependent murine myeloid cell line FDC-P1 and pro-B cell line BAF-B03, which normally do not respond to G-CSF, enabled them to proliferate in response to G-CSF. On the other hand, expression of the G-CSF receptor cDNA in the IL-2-dependent T cell line CTLL-2 did not enable it to grow in response to G-CSF, although G-CSF could transiently stimulate DNA synthesis. Mutational analyses of the G-CSF receptor in FDC-P1 cells indicated that the N-terminal half of the CRH domain was essential for the recognition of G-CSF, but the Ig-like, FNIII and cytoplasmic domains were not. The CRH domain and a portion of the cytoplasmic domain of about 100 amino acids in length were indispensable for transduction of the G-CSF-triggered growth signal.

Xylanase (xynA) and β-xylosidase (xynB) genes of Bacillus pumilus were expressed in Saccharomyces cerevisiae by using the GAP (glyceraldehyde-3-phosphate dehydrogenase) promoter of S. cerevisiae. Yeast cells harboring a plasmid pNAX2 containing xynA produced xylanase in the cytoplasm of the cell to an extent as much as 5% of the total soluble protein in the cell extract. Xylanase produced in yeast had an extra methionine at the N-terminus, but had the same specific activity as that produced by B. pumilus IPO. The xylanase in the yeast was not glycosylated and was immunologically identical to that of B. pumilus IPO. Yeast cells harboring a plasmid pYXB containing xynB produced β-xylosidase in the cytoplasm of the cell (3% of the total soluble protein). β-Xylosidase purified from the yeast strain exhibited specific activity nearly equal to the value of enzyme purified from B. pumilus, and had an N-terminal sequence identical to the sequence of the enzyme from B. pumilus.