Biomedical subjects

Shinpei Yamaguchi

Publications and source records attributed to Shinpei Yamaguchi.

7 recordsLinked to original sources

PubMed2005

First asymmetric total synthesis of synerazol, an antifungal antibiotic, and determination of its absolute stereochemistry.

[reaction: see text] By synthesizing two possible diastereomers, the first asymmetric total synthesis of synerazol, an antifungal antibiotic, has been accomplished, allowing determination of its absolute stereochemistry. A more practical second generation route was also established. The key steps are racemization-free deprotection of a TIPS group and introduction of a methyl ether by DMD oxidation of the benzylidene moiety in a substrate having a small protecting group.

Antifungal Agents↗

PubMed2005

Nanog expression in mouse germ cell development.

Nanog is a newly identified transcriptional factor bearing a homeodomain and expressed in pluripotential cells of preimplantation and early postimplantation embryos, and embryonic stem (ES) and embryonic germ (EG) cells. Knockout experiments indicate that Nanog functions as a key player in maintaining the pluripotency of stem cells. Importantly, Nanog expression is highly expressed in primordial germ cells (PGCs) of E11.5 and E12.5 mouse embryos. However, its temporal and spatial expression pattern and function in germ cells are largely unknown. To address these issues, whole embryos and cryosections of embryos were immunostained with anti-NANOG and anti-STELLA/PGC7 antibodies. NANOG expression, repressed in colonized PGCs of E7.25-E7.5 embryos, became detectable in migrating PGCs of E7.75-E8.0 embryos. Both male and female PGCs migrating in E9.5 and E10.5 embryos and colonizing the genital ridges of E11.5 and E12.5 embryos were positive for NANOG immunostaining, while the NANOG expression pattern differed between the sexes in the later developmental stage. In female gonadal PGCs of E13.5 and E14.5 embryos, NANOG became undetectable in germ cells positive for the synaptonemal complex-specific protein SCP3, while in male PGCs of E14.5-E16.5 embryos, the number of NANOG-positive germ cells drastically decreased during the mitotic arrest. No germ cells positive for NANOG were detectable in testes and ovaries of adult mice. Thus, in germ cell development, NANOG is expressed in proliferating germ cells, in which nuclear reprogramming is progressing.

Animals↗

PubMed2005

Pluripotential competence of cells associated with Nanog activity.

Nanog is a novel pluripotential cell-specific gene that plays a crucial role in maintaining the undifferentiated state of early postimplantation embryos and embryonic stem (ES) cells. We have explored the expression pattern and function of Nanog and a Nanog-homologue, Nanog-ps1.Nanog-ps1 was mapped on Chromosome 7 and shown to be a pseudogene. Immunocytochemical analysis in vivo showed that the NANOG protein was absent in unfertilized oocytes, and was detected in cells of morula-stage embryos, the inner cell mass of blastocysts and the epiblast of E6.5 and E7.5 embryos, but not in primordial germ cells of early postimplantation embryos. In monkey and human ES cells, NANOG expression was restricted to undifferentiated cells. Furthermore, reactivation of the somatic cell-derived Nanog was tightly linked with nuclear reprogramming induced by cell hybridization with ES cells and by nuclear transplantation into enucleated oocytes. Notably, mouse Nanog (+/-) ES cells, which produced approximately half the amount of NANOG produced by wild-type ES cells, readily differentiated to multi-lineage cells in culture medium including LIF. The labile undifferentiated state was fully rescued by constitutive expression of exogenous Nanog. Thus, the activity of Nanog is tightly correlated with an undifferentiated state of cells even in nuclear reprogrammed somatic cells. Nanog may function as a key regulator for sustaining pluripotency in a dose-dependent manner.

Amino Acid Sequence↗

PubMed2004

X-chromosome inactivation in differentiating mouse embryonic stem cells carrying X-linked GFP and lacZ transgenes.

Three new female ES cell lines (GLM1, GLP1 and GLP2) were established from mouse embryos carrying GFP (green fluorescent protein) and HMG-lacZ transgenes on one of two X chromosomes in cis. Using these cell lines, we studied the temporal relationships among three events relevant to X-chromosome inactivation: replication asynchrony of the X chromosome, and quenching of GFP fluorescence and beta-galactosidase (beta-gal) activity, during cell differentiation induced by embryoid body (EB) formation and retinoic acid (RA) treatment. In embryoid bodies adhering to the bottom of culture dishes, GFP-negative cells appeared first in the peripheral outgrowths 4 days after the initiation of EB formation, followed about 24 hours later by the appearance of cells negative for beta-gal and those having a single allocyclic X chromosome. Although the frequency of cells with an allocyclic X chromosome could reach 80% in adherent embryoid bodies, it tended to remain low and variable in embryoid bodies maintained in suspension. In spite of apparently parallel extinction of GFP and lacZ in embryoid bodies, their concurrent occurrence did not always characterize RA-induced differentiation. Moreover, an allocyclic X chromosome was identified in not more than 20 percent of informative metaphase cells up to 10 days after initiation of RA treatment. These findings suggest that RA-induced differentiation of female ES cells does not always accompany X-inactivation.

Animals↗

PubMed2003

Asymmetric total synthesis of pseurotin A.

The asymmetric total syntheses of pseurotin A and 8-O-demethylpseurotin A have been accomplished. Key reactions are a NaH-promoted intramolecular cyclization of an alkynylamide to form a gamma-lactam, an aldol reaction of a benzylidene-substituted ketone, and the late-stage introduction of the benzoyl group by a selective oxidation of a benzylidene moiety with dimethyldioxirane (DMD). [reaction: see text]

Benzylidene Compounds↗

PubMed2003

Preference of guinea pigs for bedding materials: wood shavings versus paper cutting sheet.

The preference of guinea pigs for bedding materials, wood shavings (WS) or paper cutting sheets (PS), was studied. Animals aged 8 weeks and 20 weeks showed a similar behaviour pattern during 30 min in the light, preferring WS to PS regardless of ages. Over both light and dark periods for 24 h, guinea pigs apparently preferred WS in the light, spending much more time resting in them than in PS. In the dark, the border-crossing was significantly more frequent than in the light, and the staying time was rather longer in PS than WS. The results suggest that guinea pigs prefer different bedding materials under light and dark conditions.

Animals↗

PubMed2002

Asymmetric total synthesis of (-)-azaspirene, a novel angiogenesis inhibitor.

The asymmetric total synthesis of (-)-azaspirene, an angiogenesis inhibitor, has been accomplished, establishing its absolute stereochemistry. The key steps are a MgBr2.OEt2-mediated, diastereoselective Mukaiyama aldol reaction, a NaH-promoted, intramolecular cyclization of an alkynylamide, and the aldol reaction of a ketone containing functionalized gamma-lactam moiety without protection of tert-alcohol and amide functionalities.

Angiogenesis Inhibitors↗