MiR-107 and MiR-185 Can Induce Cell Cycle Arrest in Human Non Small Cell Lung Cancer Cell Lines

BACKGROUND: MicroRNAs (miRNAs) are short single stranded noncoding RNAs that suppress gene expression through either translational repression or degradation of target mRNAs. The annealing between messenger RNAs and 5' seed region of miRNAs is believed to be essential for the specific suppression of target gene expression. One miRNA can have several hundred different targets in a cell. Rapidly accumulating evidence suggests that many miRNAs are involved in cell cycle regulation and consequentially play critical roles in carcinogenesis. METHODOLOGY/PRINCIPAL FINDINGS: Introduction of synthetic miR-107 or miR-185 suppressed growth of the human non-small cell lung cancer cell lines. Flow cytometry analysis revealed these miRNAs induce a G1 cell cycle arrest in H1299 cells and the suppression of cell cycle progression is stronger than that by Let-7 miRNA. By the gene expression analyses with oligonucleotide microarrays, we find hundreds of genes are affected by transfection of these miRNAs. Using miRNA-target prediction analyses and the array data, we listed up a set of likely targets of miR-107 and miR-185 for G1 cell cycle arrest and validate a subset of them using real-time RT-PCR and immunoblotting for CDK6. CONCLUSIONS/SIGNIFICANCE: We identified new cell cycle regulating miRNAs, miR-107 and miR-185, localized in frequently altered chromosomal regions in human lung cancers. Especially for miR-107, a large number of down-regulated genes are annotated with the gene ontology term 'cell cycle'. Our results suggest that these miRNAs may contribute to regulate cell cycle in human malignant tumors

Factors which enable the cooperation of the inhabitant and the mentally handicapped person : From analysis of PRECEDE－PROCEED Model

地域の中で住民と精神障害者が協働することを可能にする要因を明らかにし、住民と精神 障害者の協働を促進するための要件を見いだすことを目的として、A地区の住民と精神障害者 との協働事業をプリシード・プロシードモデル（PRECEDE－PROCEED Model）を用いて質的 研究を行った。その結果、住民と精神障害者の協働を可能にする要因として、１）地域が精 神障害者を受け入れる素地を形成すること、２）精神障害者が自ら地域に出向き自分の特性 である障害への理解を得ようとする強い願いをもつこと、３）それらにより両者が協働する 準備状態にあること、の3 点が抽出された。The purpose of this study was to examine the factors which enable the cooperation of the inhabitant and the mentally handicapped person in the community using PRECEDE-PROCEED Model . Analysis identified the following three components: １. Making the preparation to receive the mentally handicapped person in the community ２. Keeping the positive attitude to deepen the inhabitant \u27s understanding of the mentally handicap ３. Preparation being made to cooperate between the mentally handicapped person and the community These findings suggest that a professional coordinator with an ability to find and use these factors can promote the cooperation between the inhabitants and the mentally handicapped person in the community

住民と精神障害者の協働を可能にする要因 : プリシード・プロシードモデル（PRECEDE－PROCEED Model）による分析から

地域の中で住民と精神障害者が協働することを可能にする要因を明らかにし、住民と精神 障害者の協働を促進するための要件を見いだすことを目的として、A地区の住民と精神障害者 との協働事業をプリシード・プロシードモデル（PRECEDE－PROCEED Model）を用いて質的 研究を行った。その結果、住民と精神障害者の協働を可能にする要因として、１）地域が精 神障害者を受け入れる素地を形成すること、２）精神障害者が自ら地域に出向き自分の特性 である障害への理解を得ようとする強い願いをもつこと、３）それらにより両者が協働する 準備状態にあること、の3 点が抽出された。The purpose of this study was to examine the factors which enable the cooperation of the inhabitant and the mentally handicapped person in the community using PRECEDE-PROCEED Model . Analysis identified the following three components: １. Making the preparation to receive the mentally handicapped person in the community ２. Keeping the positive attitude to deepen the inhabitant 's understanding of the mentally handicap ３. Preparation being made to cooperate between the mentally handicapped person and the community These findings suggest that a professional coordinator with an ability to find and use these factors can promote the cooperation between the inhabitants and the mentally handicapped person in the community

Domoic acid biosynthesis in the red alga Chondria armata suggests a complex evolutionary history for toxin production.

Domoic acid (DA), the causative agent of amnesic shellfish poisoning, is produced by select organisms within two distantly related algal clades: planktonic diatoms and red macroalgae. The biosynthetic pathway to isodomoic acid A was recently solved in the harmful algal bloom-forming diatom Pseudonitzschia multiseries, establishing the genetic basis for the global production of this potent neurotoxin. Herein, we sequenced the 507-Mb genome of Chondria armata, the red macroalgal seaweed from which DA was first isolated in the 1950s, identifying several copies of the red algal DA (rad) biosynthetic gene cluster. The rad genes are organized similarly to the diatom DA biosynthesis cluster in terms of gene synteny, including a cytochrome P450 (CYP450) enzyme critical to DA production that is notably absent in red algae that produce the simpler kainoid neurochemical, kainic acid. The biochemical characterization of the N-prenyltransferase (RadA) and kainoid synthase (RadC) enzymes support a slightly altered DA biosynthetic model in C. armata via the congener isodomoic acid B, with RadC behaving more like the homologous diatom enzyme despite higher amino acid similarity to red algal kainic acid synthesis enzymes. A phylogenetic analysis of the rad genes suggests unique origins for the red macroalgal and diatom genes in their respective hosts, with native eukaryotic CYP450 neofunctionalization combining with the horizontal gene transfer of N-prenyltransferases and kainoid synthases to establish DA production within the algal lineages