Molecular Characterization of an Intact p53 Pathway Subtype in High-Grade Serous Ovarian Cancer

High-grade serous ovarian cancer (HGSOC) is the most aggressive histological type of epithelial ovarian cancer, which is characterized by a high frequency of somatic TP53 mutations. We performed exome analyses of tumors and matched normal tissues of 34 Japanese patients with HGSOC and observed a substantial number of patients without TP53 mutation (24%, 8/34). Combined with the results of copy number variation analyses, we subdivided the 34 patients with HGSOC into subtypes designated ST1 and ST2. ST1 showed intact p53 pathway and was characterized by fewer somatic mutations and copy number alterations. In contrast, the p53 pathway was impaired in ST2, which is characterized by abundant somatic mutations and copy number alterations. Gene expression profiles combined with analyses using the Gene Ontology resource indicate the involvement of specific biological processes (mitosis and DNA helicase) that are relevant to genomic stability and cancer etiology. In particular we demonstrate the presence of a novel subtype of patients with HGSOC that is characterized by an intact p53 pathway, with limited genomic alterations and specific gene expression profiles.     

Studies on Phenolic Lactones

Isohibalactone, the geometric isomer of hibalactone, was synthesized by the following route. Piperonylsuccinic acid anhydride was converted into thioethyl methyl ester ans was reduced to piperonylbutyrolactone by Raney nickel catalyst. Piperonylbutyrolactone was also prepared from piperonylsuccinic anhydride by the reduction with amalgamated aluminum. Condensation of piperdnal with the lactone in the presence of potassium amide afforded α-(3,4-methyIenedioxy-phenyl-hydroxymethyl)-β-(3,4-methylenedioxybenzyl)-butyrolactone, m.p. 151~2°C. Dehydration of the hydroxylactone with p-toluenesulfonic acid gave isohibalactone, m.p. 156~6.5°C.     

Studies on Phenolic Lactones

The synergistic action of phenolic lactones on allethrin and pyrethrin were investigated from the mortality of synergized pyrethroids against rice-weevil by petri-dish method.

In the series of α-benzylidene-γ-butyrolactones, (±) hibalactone and α-piperonylidenebutyrolactone were appreciably sy~ergistic on allethrin although less effective than piperonyl butoxide. (±) Hinokinin, 2-piperonylidene-3-piperonyl-l,4-butanediol also showed week activation, but α-benzylidene-, α-anisylidene-, α-veratrylidene-butyrolactone, α-piperonylidenea-α’-piperonyl-tetrahydrofuran, α-trirnethoxybenzylidene-β-trimethoxybenzyl-butyrolactone were not synergistic on the insecticidal action.

In the series of synergized pyrethrin, (±) hibalactone and α-piperonylidene-butyrolactone showed week synergism but the other test compounds showed no appreciable synergism.     

Synthetic Studies on Colchicine-related Tropolones

Pschorr reaction of 4-[3-(3,4,5-trimethoxyphenyl)-propyl]-5-amino-tropolone (VII) gave desacetamidocolchiceine (IIa), though the oxidative coupling reaction of 4-[3-(3,4-dihydroxy- 5-methoxy phenyl)-propyl]-tropolone (Xa) failed to give the same compound (IIa).     

Sex-biased natal dispersal in Hokkaido brown bears revealed through mitochondrial DNA analysis

Understanding natal dispersal patterns is fundamental in the ecology and conservation biology of large wild carnivores. In this study, we used two approaches to determine genetic variation and dispersal patterns of brown bears in the Shiretoko Peninsula, eastern Hokkaido, Japan. The first approach was a large-scale genetic analysis. We analyzed haplotypes from the mitochondrial DNA (mtDNA) control region of 760 individual samples collected throughout the peninsula during 1998–2016. We detected seven haplotypes, including two that were confirmed for the first time. In females, the distribution of haplotypes was geographically structured, whereas haplotypes in males were distributed widely throughout the peninsula. Only some males in the lower peninsula had haplotypes that were not detected within the peninsula. The second approach was a local-scale genetic analysis, including intensive focal sampling in the Rusha area, a special wildlife protection area on the peninsula. Proportions of mtDNA haplotypes in adult bears were investigated and compared between the sexes. Although more than half of the females had the same haplotype, males had more diverse haplotypes, suggesting that they came to the Rusha area from other regions. Thus, our study revealed that mtDNA haplotype distribution has been maintained by female philopatry, and that bears exhibit male-biased dispersal. Furthermore, the lower peninsula appears to act as a contact zone between the peninsula and mainland Hokkaido, which is important for maintaining genetic diversity.     

Lupin alkaloids from flowers of Echinosophora koreensis

(?)-Methyl 12-cytisineacetate (2) was isolated from methanol extracts of fresh flowers of Echinosophora koreensis together with seven known lupin alkaloids. Ethyl 12-cytisineacetate (3) was also isolated from ethanol extracts of the same flowers. Compounds 2 and 3 were artifacts and (?)-12-cytisineacetic acid (4) is assumed to be the principal source of 2 and 3. The variations in alkaloid content during growth of the flowers and the seedlings were also examined.     

On the three visual pigments in the retina of the firefly squid,Watasenia scintillans

Summary The deep-sea bioluminescent squid, Watasenia scintillans, has three visual pigments: The major one (A1 pigment) is based on retinal and has _max = 484 nm, the second one (A2 pigment) is based on 3-dehydroretinal and has _max = 500 nm, and the third one (A4 pigment) is based on 4-hydroxyretinal and has _max = 470 nm. The distribution of these 3 visual pigments in the retina was studied by HPLC analysis of the retinals in retina slices obtained by microdissection. It was found that A1 pigment was not located in the specific region of the ventral retina receiving the down-welling light which contains very long photoreceptor cells, forming two strata. A2 and A4 pigment were found exclusively in the proximal pinkish stratum and in the distal yellowish stratum. The role of these pigments in the retina is hypothesized to involve spectral discrimination. The extraction and analysis of retinoids to determine the origin of 3-dehydroretinal and 4-hydroxyretinal in the mature squid showed only a trace amount of 4-hydroxyretinol in the eggs. Similar analysis of other cephalopods collected near Japan showed the absence of A2 or A4 pigment in their eyes.Abbreviations HPLC high-performance liquid chromatography - IS inner segment - OS outer segment