For generation of energy, cancer cells utilize glycolysis more vigorously than oxidative phosphorylation in mitochondria (Warburg effect). We examined the energy metabolism of four leukemia cell lines by using glycolysis inhibitor, 2-deoxy-d-glucose (2-DG) and inhibitor of oxidative phosphorylation, oligomycin. NB4 was relatively sensitive to 2-DG (IC(50): 5.75 mM), consumed more glucose and produced more lactate (waste product of glycolysis) than the three other cell lines. Consequently, NB4 was considered as a "glycolytic" leukemia cell line. Dependency on glycolysis in NB4 was confirmed by the fact that glucose (+) FCS (-) medium showed more growth and survival than glucose (-) FCS (+) medium. Alternatively, THP-1, most resistant to 2-DG (IC(50): 16.14 mM), was most sensitive to oligomycin. Thus, THP-1 was recognized to be dependent on oxidative phosphorylation. In THP-1, glucose (-) FCS (+) medium showed more growth and survival than glucose (+) FCS (-) medium. The dependency of THP-1 on FCS was explained, at least partly, by fatty acid oxidation because inhibitor of fatty acid β-oxidation, etomoxir, augmented the growth suppression of THP-1 by 2-DG. We also examined the mechanisms by which THP-1 was resistant to, and NB4 was sensitive to 2-DG treatment. In THP-1, AMP kinase (AMPK), which is activated when ATP becomes limiting, was rapidly phosphorylated by 2-DG, and expression of Bcl-2 was augmented, which might result in resistance to 2-DG. On the other hand, AMPK phosphorylation and augmentation of Bcl-2 expression by 2-DG were not observed in NB4, which is 2-DG sensitive. These results will facilitate the future leukemia therapy targeting metabolic pathways.

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The Japanese Schizophrenia Sib-Pair Linkage Group (JSSLG) is a multisite collaborative study group that was organized to create a national resource for affected sib pair (ASP) studies of schizophrenia in Japan. We used a high-density single-nucleotide-polymorphism (SNP) genotyping assay, the Illumina BeadArray linkage mapping panel (version 4) comprising 5,861 SNPs, to perform a genomewide linkage analysis of JSSLG samples comprising 236 Japanese families with 268 nonindependent ASPs with schizophrenia. All subjects were Japanese. Among these families, 122 families comprised the same subjects analyzed with short tandem repeat markers. All the probands and their siblings, with the exception of seven siblings with schizoaffective disorder, had schizophrenia. After excluding SNPs with high linkage disequilibrium, we found significant evidence of linkage of schizophrenia to chromosome 1p21.2-1p13.2 (LOD=3.39) and suggestive evidence of linkage to 14q11.2 (LOD=2.87), 14q11.2-q13.2 (LOD=2.33), and 20p12.1-p11.2 (LOD=2.33). Although linkage to these regions has received little attention, these regions are included in or partially overlap the 10 regions reported by Lewis et al. that passed the two aggregate criteria of a meta-analysis. Results of the present study--which, to our knowledge, is the first genomewide analysis of schizophrenia in ASPs of a single Asian ethnicity that is comparable to the analyses done of ASPs of European descent--indicate the existence of schizophrenia susceptibility loci that are common to different ethnic groups but that likely have different ethnicity-specific effects.

Schizophrenia (SCZ) is a complex psychiatric disease with a lifetime morbidity rate of 0.5-1.0 %. To date, aberrant DNA methylation in SCZ has been reported in several studies. However, no comprehensive studies using medication-free subjects with SCZ have been conducted. In addition, most of these studies have been limited to the analysis of the CpG sites in CpG islands (CGIs) in the gene promoter regions, so little is known about the DNA methylation signatures across the whole genome in SCZ. Genome-wide DNA methylation profiling (485,764 CpG sites) of peripheral leukocytes was conducted in the first set of samples (24 medication-free patients with SCZ and 23 non-psychiatric controls) using Infinium HumanMethylation450 Beadchips. Second, a monozygotic twin study was performed using three pairs of monozygotic twins that were discordant for SCZ. Finally, the data from these two independent cohorts were compared. A total of 234 differentially methylated CpG sites that were common between these two cohorts were identified. Of the 234 CpG sites, 153 sites (65.4 %) were located in the CGIs and in the regions flanking CGIs (CGI: 40.6 %; CGI shore: 13.3 %; CGI shelf: 11.5 %). Of the 95 differently methylated CpG sites in the CGIs, most of them were located in the promoter regions (promoter: 75.8 %; gene body: 14.7 %; 3'-UTR: 2.1 %). Aberrant DNA methylation in SCZ was identified at numerous loci across the whole genome in peripheral leukocytes using two independent sets of samples. These findings support the notion that altered DNA methylation could be involved in the pathophysiology of SCZ.

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Ab initio MO calculations have been carried out for the unimolecular decomposition of oxalic acid. We used the Hartree-Fock (HF) method with LCAO approximation mainly using the 3-21G basis set with standard parameters to optimize the geometries for the three conformers of oxalic acid and eight probable transition states. The energy gradient technique was employed. Normal modes and vibrational frequencies were calculated by using the 3-21G basis set. It was found that the lowest energy path was (COOH)2 -* C02 + CO + H20 (2), having a five-center transition state. From the results of ab initio calculations, the first-order rate constant for channel 2 was evaluated as k2 = 1014•9 exp(-29.8 kcal mol™1/7?7) s™1, over the temperature range 300-1300 K, in terms of transition-state theory. The thermal decomposition of oxalic acid vapor diluted in Ar has been also briefly investigated behind reflected shock waves over the temperature range 850-1300 K. The decomposition was monitored by IR emission and vacuum-UV absorption from products. The decomposition product analysis was also done by gas chromatography. Although the rate constant could not be evaluated because of the very low reactant concentration and the too fast decomposition, major products observed were C02, CO, and H20, being consistent with the results of the ab initio calculations and the previous infrared multiphoton study by Yamamoto and Back.

The electronic structure of biphenyl, fulvalene, and related molecules in ground and excited states is studied. To a -electron SCF and SCF-CI calculation we couple an evaluation of the H-H repulsion to estimate torsional potential energy curves in ground and excited states. The changes in conformational preferences in excited states are easily predicted from a simple correlation diagram connecting planar and twisted molecules. Thus for two coupled q -electron systems one expects planar ground states, possibly twisted excited states, for q = An 4-1 or An + 3; planar ground or excited states, possibly triplet or quintet ground states, for q = An; possibly twisted ground states and planar excited states for q = An + 2. he molecule of biphenyl is planar or nearly so in the solid state,1 11'2 twisted some 40°around the central single bond in the vapor phase. 3 The groundstate torsion is thus clearly a delicate balance of nonbonded repulsion and conjugation, and the groundstate rotational potential has attracted some theoretical attention.4-6 There have been a number of calculations directed toward explicating the spectrum of biphenyl.7-13 These calculations probe only the ground-state geometry, and generally good agreement with experiment is obtained for twist angles correlating well with the vaporphase equilibrium geometry. That the inter-ring bond acquires some double-bond character in the lowest excited state of the molecule is an obvious conclusion from either a valence-bond14 or molecular-orbital16 viewpoint. The influence of this potential energy change on the position and intensity of electronic transitions has been ably discussed by Jaffe and Orchin.15 Recently, some stimulating experiments were reported by Wagner.16 From a study of the singlet-triplet absorption, its quenching, and the phosphorescence of biphenyl, it was concluded that in its lowest excited triplet biphenyl was planar, in contrast to its twisted ground-state equilibrium conformation.