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Cancer cells generally exhibit increased iron uptake, which contributes to their abnormal growth and metastatic ability. Iron chelators have thus recently attracted attention as potential anticancer agents. Here, we show that deferriferrichrysin (Dfcy), a natural product from Aspergillus oryzae acts as an iron chelator to induce paraptosis (a programmed cell death pathway characterized by ER dilation) in MCF‐7 human breast cancer cells and H1299 human lung cancer cells. We first examined the anticancer efficacy of Dfcy in cancer cells and found that Dfcy induced ER dilation and reduced the number of viable cells. Extracellular signal‐related kinase (ERK) was activated by Dfcy treatment, and the MEK inhibitor U0126, a small molecule commonly used to inhibit ERK activity, prevented the increase in ER dilation in Dfcy‐treated cells. Concomitantly, the decrease in the number of viable cells upon treatment with Dfcy was attenuated by U0126. Taken together, these results demonstrate that the iron chelator Dfcy exhibits anticancer effects via induction of ERK‐dependent paraptosis. [ABSTRACT FROM AUTHOR]

Hydroxyapatite adsorbs various substances, but little is known about the effects on oral bacteria of adsorption onto hydroxyapatite derived from scallop shells. In the present study, we analyzed the effects of adsorption of Streptococcus mutans onto scallop-derived hydroxyapatite. When scallop-derived hydroxyapatite was mixed with S. mutans, a high proportion of the bacterial cells adsorbed onto the hydroxyapatite in a time-dependent manner. An RNA sequencing analysis of S. mutans adsorbed onto hydroxyapatite showed that the upregulation of genes resulted in abnormalities in pathways involved in glycogen and histidine metabolism and biosynthesis compared with cells in the absence of hydroxyapatite. S. mutans adsorbed onto hydroxyapatite was not killed, but the growth of the bacteria was inhibited. Electron microscopy showed morphological changes in S. mutans cells adsorbed onto hydroxyapatite. Our results suggest that hydroxyapatite derived from scallop shells showed a high adsorption ability for S. mutans. This hydroxyapatite also caused changes in gene expression related to the metabolic and biosynthetic processes, including the glycogen and histidine of S. mutans, which may result in a morphological change in the surface layer and the inhibition of the growth of the bacteria. [ABSTRACT FROM AUTHOR]

In ascidian eggs, the existence of several localized maternal cytoplasmic determinants has been proposed and the importance of localized mRNAs for tissue differentiation has been demonstrated. We previously identified the ascidian Y-box proteins (CiYB 1, 2 and 3), homologues of which are known to be involved in the storage of maternal mRNA in oocytes of other organisms. In this study, we found that CiYB1 protein is abundant in the gonad, egg, and embryo. Purification of messenger ribonucleoprotein (mRNP) particles from the gonad revealed that CiYB1 was one of their major components. A significant change in the distribution of CiYB1 protein from stored mRNP particles in the gonad to the ribosome fraction in eggs and embryos was observed. This change correlates most likely with the shift of stored maternal mRNAs to polyribosomes. Moreover, we found that CiYB1 colocalized with Cipem and Ci-machol mRNAs, which are localized at the posterior end of the embryo at the cleavage stage. Cipem and Ci-machol mRNAs were co-immunoprecipitated with CiYB1 in the oocyte and embryo lysates. The formation of a complex between Cipem mRNA and CiYBI protein resulted in translational repression in the in vitro translation system. Our results indicate that associating with CiYB 1 protein contributes to the translational control of the localized mRNA in eggs and embryos. Keywords: Ascidian; Maternal mRNA; mRNP; Y-box protein; Local zed mRNA; Translational repression

A set of 1,378 expressed sequence tags (ESTs), both the 5'-most and 3'-most ends, derived from Ciona intestinalis fertilized eggs was categorized into 1,003 independent clusters. When compared with sequences in databases, 452 of the clusters showed significant matches with reported proteins, while 190 showed matches with putative proteins for which there is not enough information to categorize their function, and 361 had no significant similarities to known proteins. Sequence similarity analyses of the 452 clusters in relation to the biological function as well as the structure of the message population at this stage demonstrated that 3162 of them have functions that many kinds of cells use, 65 are associated with cell-cell communication, including a candidate cDNA for sonic hedgehog, and 25 are transcription factors. Sequence prevalence distribution analysis demonstrated that the great majority (78%) of the mRNAs are rare mRNAs or are represented by a single clone/cluster. All of the 1,003 clusters were subjected to whole-mount in situ hybridization to analyze the distribution of the maternal mRNAs in fertilized eggs, and a total of 329 genes showed localized distribution of the mRNAs: 16 showed cortical localization, 12 showed mitochondrial-like distribution, 99 crescent-like distribution, 63 partial localization, and 139 weak localization. When the distribution pattern of all the maternally expressed mRNAs was examined in the 8-cell stage embryos, it became evident that 248 genes which have localized mRNA patterns at the fertilized egg stage lose their localized distribution by the 8-cell stage. In contrast, 13 genes newly gain a localized pattern by the 8-cell stage. In addition, a total of 39 genes showed distinct in situ signals in the nucleus of blastomeres of the 8-cell stage embryo, suggesting early zygotic expression of these genes by this stage. These results suggest that complicated cytoplasmic movements are associated with the characteristic distribution of maternal mRNAs, which in turn support proper embryonic axis formation and establishment of the genetic network for embryonic cell specification. Key Words: Ciona; fertilized eggs; EST analysis; mRNA distribution patterns.