Novel Insights into the Interplay between Apoptosis and Autophagy

For several decades, apoptosis has taken center stage as the principal mechanism of programmed cell death (type I cell death) in mammalian tissues. Autophagic cell death (type II) is characterized by the massive accumulation of autophagic vacuoles in the cytoplasm of cells. The autophagic process is activated as an adaptive response to a variety of extracellular and intracellular stresses, including nutrient deprivation, hormonal or therapeutic treatment, pathogenic infection, aggregated and misfolded proteins, and damaged organelles. Increasing evidence indicates that autophagy is associated with a number of pathological processes, including cancer. The regulation of autophagy in cancer cells is complex since it can enhance cancer cell survival in response to certain stresses, while it can also act to suppress the initiation of cancer growth. This paper focused on recent advances regarding autophagy in cancer and the techniques currently available to manipulate autophagy

Seed Maturation Regulators Are Related to the Control of Seed Dormancy in Wheat (Triticum aestivum L.)

In Arabidopsis, the regulation network of the seed maturation program controls the induction of seed dormancy. Wheat EST sequences showing homology with the master regulators of seed maturation, LEAFY COTYLEDON1 (LEC1), LEC2 and FUSCA3 (FUS3), were searched from databases and designated respectively as TaL1L (LEC1-LIKE), TaL2L (LEC2-LIKE), and TaFUS3. TaL1LA, TaL2LA and TaFUS3 mainly expressed in seeds or embryos, with the expression limited to the early stages of seed development. Results show that tissue-specific and developmental-stage-dependent expressions are similar to those of seed maturation regulators in Arabidopsis. In wheat cultivars, the expression level of TaL1LA is correlated significantly with the germination index (GI) of whole seeds at 40 days after pollination (DAP) (r = -0.83**). Expression levels of TaFUS3 and TaL2LA are significantly correlated respectively with GIs at 40 DAP and 50 DAP, except for dormant cultivars. No correlation was found between the expression level of TaVP1, orthologue of ABA INSENSITIVE3 (ABI3), and seed dormancy. DELAY OF GERMINATION1 (DOG1) was identified as a quantitative trait locus (QTL) for the regulation of seed dormancy in Arabidopsis. Its promoter has RY motif, which is a target sequence of LEC2. Significant correlation was found between the expression of TaDOG1 and seed dormancy except for dormant cultivars. These results indicate that TaL1LA, TaL2LA, and TaFUS3 are wheat orthologues of seed maturation regulators. The expressions of these genes affect the level of seed dormancy. Furthermore, the pathways, which involve seed maturation regulators and TaDOG1, are important for regulating seed dormancy in wheat

Comparison between shoot Regeneration Ability in Calli Derived from Immature Embryos of Wild and Cultivated Barley

The variation in shoot regeneration obility of calli derived from immature embryos was examined in 95 wild strains, 82 of which were of Hordeum spontaneum and 13 of which were H. agriocrithon, and 87 cultivated varieties collected from various countries or regions of the world. In 85 strains of the wild species, a number of calli regenerated shoots, and their proportion ranged from 1.2% to 75.7%. The average percentage of shoot regenerating calli was 21.7% among the strains that formed calli, 11.5% of which regenerated green and 10.2% albino shoots. On average, 21.4% and 23.9% calli regenerated shoots in H. spontaneum and H. agriocrithon, respectively and there was no significant difference between these values. A significant difference in the percentage of shoot regenerating calli was found among six variants (dawense, ishnatherum, laguncliforme, paradoxon, proskowetzii, spontaneum) which were comprised in H. spontaneum. In 73 varieties of cultivated species, there were shoots regenerating calli likely to wild species, and their proportion ranged from 3.2% to 85.5%. The average percentage of shoot regenerating calli was 25.4%, 22.0% of which regenerated green and 3.4% of which regenerated albino shoots. There was a significant difference in percentage of green shoots regenerating calli against shoots regenerating ones between the wild (53.0%) and cultivated species 886.6%). The two kinds of non-brittle rachis genotypes, Bt bt2 and bt Bt2 are one of the key characters distinguishing the oriental and occidental types of cultivated barley. The average percentages of shoot regenerating calli were 16.2% and 32.3% for the genotypes Bt bt2 and bt Bt2, respectively, suggesting that there is a geographical variation in the shoot regeneration ability of calli in the cultivated species. By contrast, the oriental and occidental strains of wild species showed no difference in the shoot regeneration ability of calli. The geographical variation of shoot regeneration ability differed significantly between wild and cultivated species. This suggests that the geographical variation of shoot regeneration ability occurred after the cultivation of the barley was established.本研究ではオオムギ近緑野生種Hordeum spontaneum82系統とH.agriocrithon13系統、計2種95系統および世界各地の栽培種87品種を供試して、未熟胚由来カルスからの不定芽再分化能を調査し、近緑野生種と栽培種における再分化能の品種変更およびその地理的分化を比較した。近緑野生種では95系統中94系統がカルスを形成し、そのうち85系統（90.4％）が不定芽を再分化して、不定芽再分化率は系統によって1.2％から75.7％まで幅広く変異した。カルスを形成した94系統における不定芽再分化率の平均値は21.7％、緑色不定芽再分化率は11.5％、アルビノ不定芽再分化率は10.2％であった。H.spontaneumとH.agriocrithonの不定芽再分化率の平均値はそれぞれ21.4％と23.9％で、有意差は認められなかった。しかし、H.spontaneumに含まれる6品種（dawense, ishnatherum, laguncliforme, paradoxon, proskowetzii, spontaneum）の間では不定芽再分化率に差異が認められた。栽培種では供試品種のすべてがカルスを形成し、そのうち73品種（83.7％）が不定芽を再分化して、不定芽再分化率は品種によって3.2％から85.5％まで幅広く変異した。供試品種全体の不定芽再分化率の平均値は25.4％、緑色不定芽再分化率は22.0％、アルビノ不定芽再分化率は3.4％であった。このように、不定芽再分化率に対する緑色不定芽再分化率の占める割合は栽培種で86.6％、近緑野生種で53.0％となり、両者に大きな差が認められた。供試した栽培種を小穂非脱落性に関する遺伝子型によって東亜地域に多く分布するBt bt2型と西域に多く分布するbt Bt2型に分けて不定芽再分化率を比較すると、Bt bt2型の平均値は16.2％、bt Bt2型の平均値は32.3％となり、bt Bt2型の不定芽再分化率が有意に高く、地理的分化が認められた。しかし、近緑野生種では不定芽再分化能の地域間差がみられないので、オオムギの祖先種が栽培化されてから不定芽再分化能の地理的分化が生じたものと考えられる

Snow-melting process in the Greenland ice sheet as deduced from the seasonal and decadal variations of snow surface albedo

第2回極域科学シンポジウム/第34回気水圏シンポジウム 11月15日（火） 統計数理研究所 セミナー室

Rice Nudix Hydrolase OsNUDX2 Sanitizes Oxidized Nucleotides

Nudix hydrolase (NUDX) hydrolyzes 8-oxo-(d)GTP to reduce the levels of oxidized nucleotides in the cells. 8-oxo-(d)GTP produced by reactive oxygen species (ROS) is incorporated into DNA/RNA and mispaired with adenine, causing replicational and transcriptional errors. Here, we identified a rice OsNUDX2 gene, whose expression level was increased 15-fold under UV-C irradiation. The open reading frame of the OsNUDX2 gene, which encodes 776 amino acid residues, was cloned into Escherichia coli cells to produce the protein of 100 kDa. The recombinant protein hydrolyzed 8-oxo-dGTP, in addition to dimethylallyl diphosphate (DMAPP) and isopentenyl diphosphate (IPP), as did Arabidopsis AtNUDX1; whereas the amino acid sequence of OsNUDX2 had 18% identity with AtNUDX1. OsNUDX2 had 14% identity with barley HvNUDX12, which hydrolyzes 8-oxo-dGTP and diadenosine tetraphosphates. Suppression of the lacZ amber mutation caused by the incorporation of 8-oxo-GTP into mRNA was prevented to a significant degree when the OsNUDX2 gene was expressed in mutT-deficient E. coli cells. These results suggest that the different substrate specificity and identity among plant 8-oxo-dGTP-hydrolyzing NUDXs and OsNUDX2 reduces UV stress by sanitizing the oxidized nucleotides

Autophagic and Apoptotic Effects of HDAC Inhibitors on Cancer Cells

Because epigenetic alterations are believed to be involved in the repression of tumor suppressor genes and the promotion of tumorigenesis in cancers, novel compounds endowed with histone deacetylase (HDAC) inhibitory activity are an attractive therapeutic approach. Indeed, the potential of HDAC inhibitors for cancer therapy has been explored in preclinical models, and some agents approved for hematologic malignancies have reached the clinical setting. HDAC inhibitors are able to mediate the induction of both apoptosis and autophagy, which are related to anticancer activity in a variety of cancer cell lines. Given the inherent resistance to apoptosis that characterizes cancer, the targeting of alternative pathways is an attractive strategy to improve anti-tumor therapy. The activation of autophagy represents novel cancer treatment targets. This paper aims to critically discuss how the anticancer potential of HDAC inhibitors may elicit a response to human cancers through different cell pathways leading to cell death

Transcriptomic analysis of developing seeds in a wheat (Triticum aestivum L.) mutant RSD32 with reduced seed dormancy

Seed dormancy, a major factor regulating pre-harvest sprouting, can severely hinder wheat cultivation. Reduced Seed Dormancy 32 (RSD32), a wheat (Triticum aestivum L.) mutant with reduced seed dormancy, is derived from the pre-harvest sprouting tolerant cultivar, 'Norin61'. RSD32 is regulated by a single recessive gene and mutant phenotype expressed in a seed-specific manner. Gene expressions in embryos of 'Norin61' and RSD32 were compared using RNA sequencing (RNA-seq) analysis at different developmental stages of 20, 30, and 40 days after pollination (DAP). Numbers of up-regulated genes in RSD32 are equivalent in all developmental stages. However, down-regulated genes in RSD32 are more numerous on DAP20 and DAP30 than on DAP40. In central components affecting the circadian clock, homologues to the morning-expressed genes are expressed at lower levels in RSD32. However, higher expressions of homologues acting as evening-expressed genes are observed in RSD32. Homologues of Ca2+ signaling pathway related genes are specifically expressed on DAP20 in 'Norin61'. Lower expression is shown in RSD32. These results suggest that RSD32 mutation expresses on DAP20 and earlier seed developmental stages and suggest that circadian clock regulation and Ca2+ signaling pathway are involved in the regulation of wheat seed dormancy

Autophagic and apoptotic effects of HDAC inhibitors on cancer cells

Because epigenetic alterations are believed to be involved in the repression of tumor suppressor genes and the promotion of tumorigenesis in cancers, novel compounds endowed with histone deacetylase (HDAC) inhibitory activity are an attractive therapeutic approach. Indeed, the potential of HDAC inhibitors for cancer therapy has been explored in preclinical models, and some agents approved for hematologic malignancies have reached the clinical setting. HDAC inhibitors are able to mediate the induction of both apoptosis and autophagy, which are related to anticancer activity in a variety of cancer cell lines. Given the inherent resistance to apoptosis that characterizes cancer, the targeting of alternative pathways is an attractive strategy to improve anti-tumor therapy. The activation of autophagy represents novel cancer treatment targets. This paper aims to critically discuss how the anticancer potential of HDAC inhibitors may elicit a response to human cancers through different cell pathways leading to cell death

Metallic phase in the metal-intercalated higher fullerene Rb8.8(7)C84

A new material of higher fullerene, RbxC84, was synthesized by intercalating Rb metal into C-84 crystals. The RbxC(84) crystals showed a simple cubic (sc) structure with lattice constant, a, of 16.82 (2) angstrom at 6.5 K, and 16.87 (2) angstrom at 295 K. The Rietveld refinements were achieved with the space group, Pa (3) over bar, based on a model that the C-2 axis of D2d-C84 aligned along [111]. The sample composition was determined to be Rb-8.8(7) C-84. The ESR spectrum at 303 K was composed of a broad peak with peak-to-peak linewidth Delta H-pp of 220 G, and a narrow peak with Delta H-pp of 24 G. Temperature dependence of the broad peak clearly showed a metallic behavior. The metallic behavior was discussed based on a theoretical calculation. This finding of new metallic phase in a higher fullerene is the first step for a development of new types of fullerene materials with novel physical properties such as superconductivity.</p

Comparison of Regenerating Ability of Calli Derived from Mature and Immature Embryos in Barley Varieties

The callus forming ability and regenerating ability of the calli derived from mature and immature embryos of 132 barley varieties were examined. These materials were taken from a world-wide collection preserved at the Barley Germplasm Center of Okayama University. The callus forming ability varied widely according to genotype in both mature and immature embryos, but the varieties collected from Ethiopia showed low callus forming ability. Calli derived from mature embryos generally did not regenerate shoots, except for three Japanese varieties. The frequency of shoot regeneration from the calli derived from immature embryos was somewhat higher than that from those derived from mature embryos. Many of the Korean and Japanese varieties had a high shoot regenerating ability. However, few of the varieties from Ethiopia and Southwest Asia had a high shoot regenerating ability. No correlation was observed btween root regenerating ability and shoot regenerating ability of the varieties. No correlation was observed between callus proliferation and root regenerating ability between calli derived from mature and immature embryos. We could not find any difference in the shoot regenerating ability btween the two-rowed and six-rowed genotypes.本研究では世界各地のオオムギ132品種を供試して完熟胚と未熟胚からのカルス誘導と再分化能について調査し、材料植物が有する遺伝要素と、外植片の違いが再分化能のどのように関与しているかを考察した。供試品種のほとんどがカルスを形成したが、全くカルスを形成しない品種もあった。エチオピアの品種にはカルス形成の悪いものが多くみられた。完熟胚培養系ならびに未熟胚培養系ともに供試品種によってカルスの増殖量に幅広い変異があり、カルスがほとんど形成されない品種から、著しく増殖する品種まであった。カルスの形態的特徴に関しては、完熟胚培養系ではほとんどの品種が水っぽいカルスを形成したのに対して、未熟胚培養系では品種によって、水っぽいタイプ、硬くしまったタイプ、もろく崩れやすいタイプの3タイプを形成し、両培養系間に大きな差異が認められた。完熟胚培養系の場合、再分化するのはほとんどが不定根であり、不定芽を再分化したのは日本の関東二条5号、ふじ二条および紫麦の3品種だけであった。一方、未熟胚培養系では、21.2％の品種が不定芽を再分化した。不定芽を再分化した品種は朝鮮半島や日本に多く、反対にエチオピアや西南アジアの品種には再分化するものが少なかった。供試品種における不定根の再分化率と不定芽の再分化率の間には相関関係はなかった。（r＝0.05）。両培養系の間ではカルス増殖量について相関関係はなく（r＝0.07）、不定根の再分化率については低い値ではあるが有意な正の相関があった（r＝0.24）。また、未熟胚培養系におけるカルス増殖量と不定芽の再分化率についても相関関係は認められなかった（r＝0.14）。二条品種と六条品種の間では、完熟胚培養系の不定根再分化率を除いて差は認められなかった