Inhibitory effects of vitamin K3 on DNA polymerase and angiogenesis

Vitamins play essential roles in cellular reactions and maintain human health. Recent studies have revealed that some vitamins including D3, B6 and K2 and their derivatives have an anti-cancer effect. As a mechanism, their inhibitory effect on cancer-related angiogenesis has been demonstrated. Vitamin K2 (menaquinones) has an anti-cancer effect in particular for hepatic cancer and inhibits angiogenesis. In the current study, we demonstrated that sole vitamin K3 (menadione) selectively inhibits the in vitro activity of eukaryotic DNA polymerase γ, which is a mitochondrial DNA polymerase, and suppresses angiogenesis in a rat aortic ring model. The anti-angiogenic effect of vitamin K3 has been shown in angiogenesis models using human umbilical vein endothelial cells (HUVECs) with regard to HUVEC growth, tube formation on reconstituted basement membrane and chemotaxis. These results suggest that vitamin K3 may be a potential anti-cancer agent like vitamin K2.This work was supported by the ‘Academic Frontier’ Project for Private Universities (Kobe-Gakuin University), matching fund subsidy from MEXT, 2006-2010, (K.M., H.Y. and Y.M.) and in part by a grant from the Japanese Ministry of Education, Culture, Sports, Science and Technology (MEXT). K.M. acknowledges a Grant-in-Aid for Young Scientists (B) (No. 18700608) from MEXT. Y.M. also acknowledges a Grant-in-Aid for Young Scientists (A) (No. 19680031) from MEXT, and Grants-in-Aid from the Nakashima Foundation and the Foundation of Oil & Fat Industry, Kaikan, Japan

De novo NSF mutations cause early infantile epileptic encephalopathy

N‐ethylmaleimide‐sensitive factor (NSF) plays a critical role in intracellular vesicle transport, which is essential for neurotransmitter release. Herein, we, for the first time, document human monogenic disease phenotype of de novo pathogenic variants in NSF, that is, epileptic encephalopathy of early infantile onset. When expressed in the developing eye of Drosophila, the mutant NSF severely affected eye development, while the wild‐type allele had no detectable effect under the same conditions. Our findings suggest that the two pathogenic variants exert a dominant negative effect. De novo heterozygous mutations in the NSF gene cause early infantile epileptic encephalopathy

Aerobic exercise training enhances cerebrovascular pulsatility response to acute aerobic exercise in older adults

The brain\u27s low resistance ensures a robust blood flow throughout systole and diastole and is susceptible to flow pulsatility. Increased cerebral pulsatility contributes to the progression of cerebrovascular disease. Although aerobic exercise affects vascular function, little is known about the effect of exercise on the cerebral pulsatility index in older adults. The aim of this study was to investigate the effect of exercise training on the post‐exercise cerebral pulsatility response in older adults. Ten healthy older adults participated in a 12‐week exercise training intervention. Before and after the intervention, we measured the pulsatility index of the middle cerebral artery by means of transcranial Doppler method at baseline and following a cycling exercise bout performed at an intensity corresponding to the ventilatory threshold. Before exercise training, there was no significant change in the cerebral pulsatility response to an acute bout of cycling exercise. However, after the intervention, cerebral pulsatility decreased significantly following 30 min of an acute cycling exercise (P < 0.05). This study demonstrated that cerebral pulsatility index did not change following an acute bout of cycling exercise at an intensity corresponding to ventilatory threshold, but that, after 12 weeks of exercise training, cerebral pulsatility index was reduced at 30 min after a single bout of cycling exercise. These results suggest that long‐term aerobic exercise training may enhance the post‐exercise reduction in pulsatility index in older adults

Full-Length Transcriptome Analysis of Human Retina-Derived Cell Lines ARPE-19 and Y79 Using the Vector-Capping Method

PURPOSE. To collect an entire set of full-length cDNA clones derived from human retina-derived cell lines and to identify full-length transcripts for retinal preferentially expressed genes. METHODS. The full-length cDNA libraries were constructed from a retinoblastoma cell line, Y79, and a retinal pigment epithelium cell line, ARPE-19, using the vector-capping method, which generates a genuine full-length cDNA. By single-pass sequencing of the 5Ј-end of cDNA clones and subsequent mapping to the human genome, the authors determined their transcriptional start sites and annotated the cDNA clones. RESULTS. Of the 23,616 clones isolated from Y79-derived cDNA libraries, 19,229 full-length cDNA clones were identified and classified into 4808 genes, including genes of Ͼ10 kbp. Of the 7067 genes obtained from the Y79 and ARPE-19 libraries, the authors selected 72 genes that were preferentially expressed in the eye, of which 131 clones corresponding to 57 genes were fully sequenced. As a result, we discovered many variants that were produced by different transcriptional start sites, alternative splicing, and alternative polyadenylation. CONCLUSIONS. The bias-free, full-length cDNA libraries constructed using the vector-capping method were shown to be useful for collecting an entire set of full-length cDNA clones for these retinal cell lines. Full-length transcriptome analysis of these cDNA libraries revealed that there were, unexpectedly, many transcript variants for each gene, indicating that obtaining the full-length cDNA for each variant is indispensable for analyzing its function. The full-length cDNA clones (approximately 80,000 clones each for ARPE-19 and Y79) will be useful as a resource for investigating the human retina. (Invest Ophthalmol Vis Sci. 2011;52:6662-6670

誤嚥性肺炎のための胃ろう増設をおこなった高齢者家族の意思決定プロセス

本研究は、摂食・嚥下障害による誤嚥性肺炎のある高齢者の家族が、どのような思いを体験し、胃ろう造設を決断したか、その意思決定プロセスを明らかにすることを目的とした。胃ろう造設を決断した高齢者家族の3事例を対象とし、意思決定プロセスについて質的に分析をした。その結果、高齢者家族の意思決定プロセスとして、＜家族の胃ろう造設という現実に向き合う＞、＜揺らぎ＞、＜胃ろう造設の意味づけ＞、＜決定へと段取り＞、＜家族としての決定＞の5つのカテゴリーを抽出した。高齢者家族は、家族の胃ろう造設という現実に向き合い、胃ろう造設の意味づけを行う中で、揺らぎのプロセスを体験していた

Gene Organization in Rice Revealed by Full-Length cDNA Mapping and Gene Expression Analysis through Microarray

Rice (Oryza sativa L.) is a model organism for the functional genomics of monocotyledonous plants since the genome size is considerably smaller than those of other monocotyledonous plants. Although highly accurate genome sequences of indica and japonica rice are available, additional resources such as full-length complementary DNA (FL-cDNA) sequences are also indispensable for comprehensive analyses of gene structure and function. We cross-referenced 28.5K individual loci in the rice genome defined by mapping of 578K FL-cDNA clones with the 56K loci predicted in the TIGR genome assembly. Based on the annotation status and the presence of corresponding cDNA clones, genes were classified into 23K annotated expressed (AE) genes, 33K annotated non-expressed (ANE) genes, and 5.5K non-annotated expressed (NAE) genes. We developed a 60mer oligo-array for analysis of gene expression from each locus. Analysis of gene structures and expression levels revealed that the general features of gene structure and expression of NAE and ANE genes were considerably different from those of AE genes. The results also suggested that the cloning efficiency of rice FL-cDNA is associated with the transcription activity of the corresponding genetic locus, although other factors may also have an effect. Comparison of the coverage of FL-cDNA among gene families suggested that FL-cDNA from genes encoding rice- or eukaryote-specific domains, and those involved in regulatory functions were difficult to produce in bacterial cells. Collectively, these results indicate that rice genes can be divided into distinct groups based on transcription activity and gene structure, and that the coverage bias of FL-cDNA clones exists due to the incompatibility of certain eukaryotic genes in bacteria