The Polymorphism of YWHAE,a Gene Encoding 14-3-3Epsilon,and Brain Morphology in Schizophrenia: A Voxel-Based Morphometric Study

Background

YWHAE is a possible susceptibility gene for schizophrenia that encodes 14-3-3epsilon, a Disrupted-in-Schizophrenia 1 (DISC1)-interacting molecule, but the effect of variation in its genotype on brain morphology remains largely unknown.

Methods

In this voxel-based morphometric magnetic resonance imaging study, we conducted whole-brain analyses regarding the effects of YWHAE single-nucleotide polymorphisms (SNPs) (rs28365859, rs11655548, and rs9393) and DISC1 SNP (rs821616) on gray matter volume in a Japanese sample of 72 schizophrenia patients and 86 healthy controls. On the basis of a previous animal study, we also examined the effect of rs28365859 genotype specifically on hippocampal volume.

Results

Whole-brain analyses showed no significant genotype effect of these SNPs on gray matter volume in all subjects, but we found significant genotype-by-diagnosis interaction for rs28365859 in the left insula and right putamen. The protective C allele carriers of rs28365859 had a significantly larger left insula than the G homozygotes only for schizophrenia patients, while the controls with G allele homozygosity had a significantly larger right putamen than the C allele carriers. The C allele carriers had a larger right hippocampus than the G allele homozygotes in schizophrenia patients, but not in healthy controls. No significant interaction was found between rs28365859 and DISC1 SNP on gray matter volume.

Conclusions

These different effects of the YWHAE (rs28365859) genotype on brain morphology in schizophrenia and healthy controls suggest that variation in its genotype might be, at least partly, related to the abnormal neurodevelopment, including in the limbic regions, reported in schizophrenia. Our results also suggest its specific role among YWHAE SNPs in the pathophysiology of schizophrenia.     

Genetic diversity,structure, and demography of Pandanus boninensis (Pandanaceae) with sea drifted seeds,endemic to the Ogasawara Islands of Japan: Comparison between young and old islands

Pandanus boninensis, endemic to the Ogasawara Islands, Japan, is distributed on both the older Bonin and younger Volcano Islands. In this study, we conducted population genetic analyses of P. boninensis on these islands to examine the population diversity and structure across old and young islands, to assess potential differences in population demography with island age, and to collect any evidence of migration between old and young islands. We found that the genetic diversity of expressed sequence tag (EST)–based microsatellite (SSR) markers, the nucleotide diversity of nuclear DNA sequences, and the haplotype diversity of chloroplast DNA on young islands were lower than those on old islands. Clustering analyses of EST‐SSR indicated that populations on old islands were strongly diverged from those on young islands. Approximate Bayesian computation analysis of EST‐SSR suggested that population expansion occurred on old islands while population reduction occurred on young islands. We also found evidence of migration among old islands (mostly from south to north), while it appears that there have been very few migration events between old and young islands. These differences could be due to the fact that young islands tend to be geographically isolated and support smaller populations that began a shorter time ago from limited founders. The P. boninensis populations on the Volcano Islands are interesting from an evolutionary perspective as they constitute a classic example of the early stages of progressive colonization on oceanic islands with small effective population sizes and low genetic diversity.     

Interaction with IQGAP1 links APC to Rac1, Cdc42, and actin filaments during cell polarization and migration

Rho family GTPases, particularly Rac1 and Cdc42, are key regulators of cell polarization and directional migration. Adenomatous polyposis coli (APC) is also thought to play a pivotal role in polarized cell migration. We have found that IQGAP1, an effector of Rac1 and Cdc42, interacts directly with APC. IQGAP1 and APC localize interdependently to the leading edge in migrating Vero cells, and activated Rac1/Cdc42 form a ternary complex with IQGAP1 and APC. Depletion of either IQGAP1 or APC inhibits actin meshwork formation and polarized migration. Depletion of IQGAP1 or APC also disrupts localization of CLIP-170, a microtubule-stabilizing protein that interacts with IQGAP1. Taken together, these results suggest a model in which activation of Rac1 and Cdc42 in response to migration signals leads to recruitment of IQGAP1 and APC which, together with CLIP-170, form a complex that links the actin cytoskeleton and microtubule dynamics during cell polarization and directional migration.     

Quantitative Structure-Activity Relationships for Antifungal 3-(3,5-Dichloropheny)-2,4-imidazolidinediones

The antifungal activity of 441-acyl derivatives of 3-(3,5-dichlorophenyl)-2,4-imidazol- idinedione against Botrytis cinerea, and of 10 1-sulfonyl compounds against Aiternaria kikuchi- ana were assayed by the agar medium dilution method. The structure-activity relationships for the substituents of the acyl and sulfonyl moieties were analyzed with such physicochemical parameters as hydrophobic π, inductive electronic σ₁, and steric E′^c_s and B₁ values by multiple regression. The activity of the acyl derivatives against B. cinerea was related parabolically to the hydrophobicity of the substituents. The stronger the electron-donating power, the larger the overall steric bulkiness, and the smaller the minimum width in the direction perpendicular to the bond axis of the substituents, the greater was the activity. The activity of the sulfonyl derivatives against A. kikuciana was related only to the hydrophobicity of the substituents.     

Stimulation of auxin-induced elongation of cucumber hypocotyl sections by dihydroconiferyl alcohol. Dihydroconiferyl alcohol inhibits indole-3-acetic acid degradation in vivo and in vitro

The mechanism by which dihydroconiferyl alcohol (DCA) stimulatesindole-3-acetic acid (IAA)-induced elongation of cucumber hypocotylsections was studied. Although DCA did not affect the uptakeof IAA-5-³H by hypocotyl sections, the endogenous level of IAA-5-³Hin DCA-treated sections was much higher than in DCA untreatedones. IAA-5-³H in the incubation medium was degraded in thepresence of hypocotyl sections, and this degradation of IAAwas inhibited by DCA. An in vitro experiment with horseradishperoxidase revealed that DCA inhibited the IAA degrading activityof the oxidase, as did caffeic acid and ferulic acid. Theseresults suggested that DCA enhances IAA-induced cucumber hypocotylelongation by acting as an antioxidant of IAA. (Received June 4, 1975; )     

Contamination of public facilities with Dermatophagoides mites (Acari: Phyroglyphidae) in Japan

The distribution of allergenic mites, Dermatophagoides farinae and Dermatophagoides pteronyssinus, was surveyed among public facilities in Japan, in order to assess the risk of people, including allergic patients, being exposed to mite allergens outside homes. Dust samples were collected using a vacuum cleaner from bedclothes, floors and other materials in four hospitals, two hotels, two ryokans, one film theatre and four office buildings. Fine dust fractions of these samples were examined for mite antigens by enzyme-linked immunosorbent assay. Overall, clinically important antigen levels of 50 g m–2 (corresponding to approximately 500 mites m–2) or more were detected in 71% of samples from chairs in a film theatre and 42% of samples from tatami and carpet floors of ryokans, whereas such serious mite contamination was not observed in samples from hospitals, hotels and offices. High mean antigen levels were observed in chairs in a film theatre (98.2 g m–2) and floors of ryokans (81.4 g m–2), whereas samples from other facilities showed mean antigen levels of <11 g m–2. Hospitals had individual antigen levels of 50 g m–2 in 2% of mattresses and 5% of painted and tiled floors but not in comforters, futons and pillows. No samples obtained from bedclothes in hotels and ryokans had antigen levels of 50 g m–2. In office buildings where the air was fully controlled by a central air-conditioning system all the year round, 99% of samples showed low antigen levels of <10 g m–2. © Rapid Science Ltd. 1998     

Enamel matrix derivative is a potent inhibitor of breast cancer cell attachment to bone

This study examined whether enamel matrix derivative (EMD) inhibits the adhesion of cancer cells to bone. A typical breast cancer cell line, MCF-7, was used. Conditioned human osteosarcoma cell (Saos-2) medium was used as extracellular bone matrix (ECBM) to measure cell attachment. MCF-7 cells were incubated on ECBM-coated culture plates with or without soluble EMD, Arg-Gly-Asp (RGD) sequence blocking peptides, recombinant bone sialoprotein (rBSP), or specific integrin antibodies, and the attached cells were quantified using toluidine blue staining. EMD markedly reduced the attachment of MCF-7 cells to ECBM in a dose-dependent manner. An RGD peptide (GRGDSP) and recombinant BSP inhibited cell attachment to the same degree as EMD. Similarly, anti-alphavbeta3 integrin antibody strongly reduced cell attachment, whereas anti-alphavbeta5 and anti-beta1 integrin antibodies had less marked effects on cell attachment. These results show that EMD inhibits MCF-7 cell attachment to a bone matrix and that it might be useful as an anti-adhesive agent for breast cancer cells to bone in vivo.     

Complete Genome Sequence of Finegoldia magna, an Anaerobic Opportunistic Pathogen

Finegoldia magna (formerly Peptostreptococcus magnus), a memberof the Gram-positive anaerobic cocci (GPAC), is a commensalbacterium colonizing human skin and mucous membranes. Moreover,it is also recognized as an opportunistic pathogen responsiblefor various infectious diseases. Here, we report the completegenome sequence of F. magna ATCC 29328. The genome consistsof a 1 797 577 bp circular chromosome and an 189 163bp plasmid (pPEP1). The metabolic maps constructed based onthe genome information confirmed that most F. magna strainscannot ferment most sugars, except fructose, and have variousaminopeptidase activities. Three homologs of albumin-bindingprotein, a known virulence factor useful for antiphagocytosis,are encoded on the chromosome, and one albumin-binding proteinhomolog is encoded on the plasmid. A unique feature of the genomeis that F. magna encodes many sortase genes, of which substratesmay be involved in bacterial pathogenesis, such as antiphagocytosisand adherence to the host cell. The plasmid pPEP1 encodes sevensortase and seven substrate genes, whereas the chromosome encodesfour sortase and 19 substrate genes. These plasmid-encoded sortasesmay play important roles in the pathogenesis of F. magna byenriching the variety of cell wall anchored surface proteins.