Synthetic Study on Polyhydroxyestrogens Modeled for Inagami-Tamura Endogenous Digitalis-like Factor and Their Activity

1 Results Mammalian possess receptors for digitalis,cardiac glycosides,derived from plants.As one of the results from studies on a real endogenous ligand for the receptors,so called an endogenous digitalis-like factor (EDF) or substance (EDS),Inagami and Tamura isolated a promising candidate possessing a molecular weight,336.We elucidated several possible structures (Fig.1) for the factor and synthesized several modeled compounds,some of which exhibited remarkable constriction at higher concentrations t...     

Regulation of IgA production by naturally occurring TNF/iNOS-producing dendritic cells

Immunoglobulin-A has an irreplaceable role in the mucosal defence against infectious microbes. In human and mouse, IgA-producing plasma cells comprise approximately 20% of total plasma cells of peripheral lymphoid tissues, whereas more than 80% of plasma cells produce IgA in mucosa-associated lymphoid tissues (MALT). One of the most biologically important and long-standing questions in immunology is why this 'biased' IgA synthesis takes place in the MALT but not other lymphoid organs. Here we show that IgA class-switch recombination (CSR) is impaired in inducible-nitric-oxide-synthase-deficient (iNOS-/-; gene also called Nos2) mice. iNOS regulates the T-cell-dependent IgA CSR through expression of transforming growth factor-beta receptor, and the T-cell-independent IgA CSR through production of a proliferation-inducing ligand (APRIL, also called Tnfsf13) and a B-cell-activating factor of the tumour necrosis factor (TNF) family (BAFF, also called Tnfsf13b). Notably, iNOS is preferentially expressed in MALT dendritic cells in response to the recognition of commensal bacteria by toll-like receptor. Furthermore, adoptive transfer of iNOS+ dendritic cells rescues IgA production in iNOS-/- mice. Further analysis revealed that the MALT dendritic cells are a TNF-alpha/iNOS-producing dendritic-cell subset, originally identified in mice infected with Listeria monocytogenes. The presence of a naturally occurring TNF-alpha/iNOS-producing dendritic-cell subset may explain the predominance of IgA production in the MALT, critical for gut homeostasis.     

Construction of a thin film PO2-electrode using gold paste

A thin film gold electrode for biological oxygen consumption was constructed using gold paste. This electrode is easy to construct, has high sensitivity and is disturbed only slightly by bubbling of the surrounding fluid. As an application, the electrode was used to measure oxygen consumption of the skin and yielded a reasonable value.     

Structural differences between a ras oncogene protein and the normal protein

One of the most commonly found transforming ras oncogenes in human tumours has a valine codon replacing the glycine codon at position 12 of the normal c-Ha-ras gene. To understand the structural reasons behind cell transformation arising from this single amino acid substitution, we have determined the crystal structure of the GDP-bound form of the mutant protein, p21(Val-12), encoded by this oncogene. We report here the overall structure of p21(Val-12) at 2.2 A resolution and compare it with the structure of the normal c-Ha-ras protein. One of the major differences is that the loop of the transforming ras protein that binds the beta-phosphate of the guanine nucleotide is enlarged. Such a change in the 'catalytic site' conformation could explain the reduced GTPase activity of the mutant, which keeps the protein in the GTP bound 'signal on' state for a prolonged period time, ultimately causing cell transformation.     

How to form and close the brain: insight into the mechanism of cranial neural tube closure in mammals

The development of the embryonic brain critically depends on successfully completing cranial neural tube closure (NTC). Failure to properly close the neural tube results in significant and potentially lethal neural tube defects (NTDs). We believe these malformations are caused by disruptions in normal developmental programs such as those involved in neural plate morphogenesis and patterning, tissue fusion, and coordinated cell behaviors. Cranial NTDs include anencephaly and craniorachischisis, both lethal human birth defects. Newly emerging methods for molecular and cellular analysis offer a deeper understanding of not only the developmental NTC program itself but also mechanical and kinetic aspects of closure that may contribute to cranial NTDs. Clarifying the underlying mechanisms involved in NTC and how they relate to the onset of specific NTDs in various experimental models may help us develop novel intervention strategies to prevent NTDs.     

Reactions of Benzo[ b ]cyclobuta[ d ]pyran-3-one Derivatives with Sulfur Ylide

1 Introduction Small ring size cycloalkanes such as cyclopropanes and cyclobutanes have been found as a basic structural constituent in a wide rang of natural products~([1]). In organic synthesis, their cycloalkanes also play an important role owing to their diversity of reaction.1IntroductionSmall ring size cycloalkanes such as cyclopropanes and cyclobutanes have beenfound as a basic structuralconstituent in a wide rang of natural products[1].In organic synthesis ,their cycloalkanes also pla…