This review paper deals with an overview of molecule-based magnetism as a rapidly developing interdisciplinary field, topological symmetry rule as the first principle of spin alignment in organic open-shell systems in the ground state, the proposal of organic through-bond 1D and 2D ferro- and super-paramagnets and the detection of the first organic high-spin molecule, m-phenylenebis(phenylmethylene) in the quintet ground state (S = 2), followed by extended organic high-spin systems with π-conjugation such as aromatic hydrocarbons having S = 3, 4, 5. The paper also describes a theoretical approach to the understanding of electronic spin structures of organic high-spin molecules by invoking both Heisenberg and Hubbard model Hamiltonians, weakly interacting intramolecular high-spin systems from both experimental and theoretical sides, the spin density distribution of the first organic high-spin molecule in terms of electron-nuclear multiple resonance spectroscopy and the detection and characterization of ionic high-spin hydrocarbons, emphasizing the establishment of high spin chemistry underlying organic molecular magnetism.
(Communicated by Hiroo INOKUCHI, M.J.A., Feb. 12, 2004)
Transition to ferromagnetic order was found in the early 1990's with a crystal of a purely organic compound without any metallic elements. The process of the research is reviewed starting from the pre-stage study to obtain the designing strategies to bring out ferromagnetic interaction in organic crystal and ending at the discovery of the ferromagnetism in the crystal of p-nitrophenyl nitronyl nitroxide (p-NPNN; C13H16N3O4).
(Communicated by Hiroo INOKUCHI, M.J.A., Feb. 12, 2004)
Here we present results obtained in our group from cell-based screenings of microbial secondary metabolites using intact microbial and mammalian cells having specific functions. We present summaries of the following five categories of compounds and the strategies that were used to identify them. (1) Antibacterial agents targeting cell wall peptidoglycan synthesis as well as active agents against organisms other than bacteria were identified by a combination of Bacillus subtilis and Mycoplasma as test organisms. (2) Antimetabolites, such as herbicidal agents targeting glutamine synthase, were identified using B. subtilis grown on minimal medium with or without the addition of glutamine and folate inhibitors by combination of B. subtilis and Enterococcus faecium, which have distinct folate metabolic pathways. (3) Among inhibitors of lipid metabolism, acyl-CoA synthetase inhibitors were identified using two mutants of C. lipolytica with different deletion sites in the fatty acid metabolic pathways, HMG-CoA synthase inhibitors were identified using Vero cells cultured in the presence and absence of mevalonate, and anti-atherosclerosis agents were identified using macrophages. (4) IL-6 inhibitors were detected by a combination of IL-6-dependent and independent murine hybridoma MH60 cells, and (5) Small molecules with TNF-like activities were identified using a mouse neuroblastoma cell line. Some advantages of such screening method and the significance of the identified compounds are discussed.
(Contributed by Satoshi OMURA, M.J.A., Feb. 12, 2004)
In 1967, a THz wave was generated for the first time using a free electron laser; however, the device was too expensive to be used widely. The author published the idea of THz wave generation by use of resonating vibration between paired atoms in polymer or crystal in 1965, and succeeded with K. Suto to generate a 12 THz wave in 1983. In 1999, the author invited K. Kawase and H. Ito to Sendai RIKEN to realize the concept by use of dielectrics; in 2000, they succeeded in realizing a sweep generator. In the same year, the author suggested the idea of applying the THz wave to cancer diagnosis and treatment, particularly by improving heating selectivity: This enhances the effect of medications by raising only the temperature of the cancer itself, not of the surrounding atomic pairs in the neighborhood. These applications are expected to spread quickly as powerful methodology based on molecular science. The reason for this is that the much improved waveform generated enables higher selectivity, allowing the detection of the existence of abnormal polymer near the paired atoms by measuring resonating frequency between paired atoms.
(Contributed by Jun-ichi NISHIZAWA, M.J.A., Jan. 13, 2004)
N-Acetylglucosaminyltransferase V (GnT-V), N-acetylglucosaminyltransferase III (GnT-III) and α1-6 fucosyltransferase (Fut8) catalyze reactions that form biologically important branching N-linked sugar chains in glycoproteins. The above three branching N-glycan sugar chains, β1-6 GlcNAc branching, bisecting GlcNAc and core fucose (α1-6 fucose), play major roles in cancer invasion and metastasis, the inhibition of cancer metastasis, and antibody-dependent cellular cytotoxicity (ADCC), growth and development, respectively. A functional glycomic approach identified the gain- and loss-of-functions of glycoproteins as the result of the aberrant glycosylation. A membrane-type metal dependent serine proteinase designated matriptase which contains β1-6 GlcNAc branching became resistant to auto-digestion and proteolysis by trypsin, and resulted in a constitutively active form which might be implicated in cancer invasion and metastasis. GnT-V also acts as an angiogenic factor without the mediation of functions as a glycosyltransferase. Recently, a GnT-V homologue, GnT-IX has been identified. This gene is expressed at relatively high levels in the brain and acts on N-glycans to form a unique branched structure, as well as O-mannosyl glycans. The addition of bisecting GlcNAc to various signaling molecules or adhesion molecules suppresses cancer metastasis. Fut8 knock-out mice, due to the lack of a core fucose (α1-6 fucose) in target glycoproteins, show disorders in growth and development. The presence of a bisecting GlcNAc or the absence of a core fucose in IgG molecules enhances ADCC activity for killing tumor cells by up to 10 to 100 fold and therefore is thought to have considerable use in antibody therapy against cancer. These data clearly indicate that gain- and loss-of-functions of target proteins for these glycosyltransferases are biologically important.
(Communicated by Tamio YAMAKAWA, M.J.A., Feb. 12, 2004)
Mobility shift of single-stranded DNA molecules with a single-base substitution in polyacrylamide gel electrophoresis due to a change of secondary and tertiary structures provides a simple, sensitive method, single-strand conformation polymorphism (SSCP) analysis, for detection of nucleotide sequence changes in DNA. The method with the quite unique principle can detect single-nucleotide substitutions, insertions or deletions of a short nucleotide sequence and loss of genes in human cancers and other genetic diseases. The great progress of the Human Genome Project has revealed thousands of genes associated with these diseases and led to an increasing need for detection of mutations and SNPs in large numbers of DNA samples. The recent development of high-throughput SSCP technologies will enable to meet this need even in a clinical setting.
(Communicated by Shoji SHIBATA, M.J.A., Feb. 12, 2004)
In 1707, approximately 0.7 km3 of magma erupted from new vents on the southeastern slope of Fuji volcano. The air-fall clasts of this explosive eruption are composed of vesicular dacite pumice, andesitic dense scoria, basaltic dense scoria, and vesiculated basalt scoria, stratified from bottom to the top of the fallout unit. Some compositional gaps are found in the variation from basalt to dacite indicating that three independent magmas, basalt, andesite and dacite, existed just prior to the eruption. Andesite and dacite magmas are mixed just prior to or during the eruption showing a linear two component mixing in the major and trace element concentration. Basalt in the later stage of the eruption shows no compositional affinity with the above two magmas. Basalt magma might have acted as a heat source to remobilize the andesite and dacite magmas, and the explosive eruption of basalt could have been caused by the abrupt pressure release due to precursory mixing and eruption of dacite and andesite magmas.
(Communicated by Ikuo KUSHIRO, M.J.A., Feb. 12, 2004)
Histidine residues added to the N-terminus of a polypeptide (i.e. a His-tag) was used, for the first time to our knowledge, for electron labeling of the protein upon its electron spectroscopic imaging. Originally such a His-tag was developed by another group to purify modified proteins by taking advantage of their affinity to nickel. The feast/famine regulatory protein pot0434017 (FL11) was modified by adding six His residues to its N-terminus, so that each His pair would chelate a nickel ion. An electron microscope was operated at 200 KeV, and the electrons that lost the energy by ~875 eV upon interaction with the metal were selectively focused. The majority, 60-70%, of the spots detected in the electron micrographs were paired by distances shorter than 80 Å and over 70% of them were paired by distances shorter than 40 Å It is concluded that the protein molecules formed dimers, and the termini of most of the protein molecules were labeled with nickel by this method.
(Communicated by Masanori OTSUKA, M.J.A., Feb. 12, 2004)
Poly(ADP-ribose) polymerase-1 (Parp-1) is involved in DNA repair and cell-death induction after DNA damage. Parp-1-/- mice show higher susceptibility to the carcinogenic effects of nitrosamine and azoxymethane. To elucidate the role of alterations of the PARP-1 gene in human carcinogenesis, we examined the expression level of PARP-1 gene in various human tumor cell lines. The presence of gross rearrangement of PARP-1 gene in these cell lines was also examined by Southern blot hybridization analysis. The expression levels of PARP-1 gene in several cell lines, including T-cell leukemia cell lines (Molt-4 and CCRF-CEM), colon cancer cell line (WiDr), and gastric cancer cell lines (KatoIII, OKAJIMA, and MKN45) was substantially lower than in other cancer cell lines. Among the 85 analyzed cell lines, structural alteration of PARP-1 gene was detected in a gastric cancer cell line, MKN28. A low level of PARP-1 expression in human cancer could potentially influence cancer cell growth, differentiation and cancer development by affecting genomic instability, as well as the response of tumors to chemo- and radiotherapy.
(Contributed by Takashi SUGIMURA, M.J.A., Feb. 12, 2004)