Profiling ascidian promoters as the primordial type of vertebrate promoter

<p>Abstract</p> <p>Background</p> <p>CpG islands are observed in mammals and other vertebrates, generally escape DNA methylation, and tend to occur in the promoters of widely expressed genes. Another class of promoter has lower G+C and CpG contents, and is thought to be involved in the spatiotemporal regulation of gene expression. Non-vertebrate deuterostomes are reported to have a single class of promoter with high-frequency CpG dinucleotides, suggesting that this is the original type of promoter. However, the limited annotation of these genes has impeded the large-scale analysis of their promoters.</p> <p>Results</p> <p>To determine the origins of the two classes of vertebrate promoters, we chose <it>Ciona intestinalis</it>, an invertebrate that is evolutionarily close to the vertebrates, and identified its transcription start sites genome-wide using a next-generation sequencer. We indeed observed a high CpG content around the transcription start sites, but their levels in the promoters and background sequences differed much less than in mammals. The CpG-rich stretches were also fairly restricted, so they appeared more similar to mammalian CpG-poor promoters.</p> <p>Conclusions</p> <p>From these data, we infer that CpG islands are not sufficiently ancient to be found in invertebrates. They probably appeared early in vertebrate evolution via some active mechanism and have since been maintained as part of vertebrate promoters.</p

Aggregation of scaffolding protein DISC1 dysregulates phosphodiesterase 4 in Huntington’s disease

Huntington’s disease (HD) is a polyglutamine (polyQ) disease caused by aberrant expansion of the polyQ tract in Huntingtin (HTT). While motor impairment mediated by polyQ-expanded HTT has been intensively studied, molecular mechanisms for nonmotor symptoms in HD, such as psychiatric manifestations, remain elusive. Here we have demonstrated that HTT forms a ternary protein complex with the scaffolding protein DISC1 and cAMP-degrading phosphodiesterase 4 (PDE4) to regulate PDE4 activity. We observed pathological cross-seeding between DISC1 and mutant HTT aggregates in the brains of HD patients as well as in a murine model that recapitulates the polyQ pathology of HD (R6/2 mice). In R6/2 mice, consequent reductions in soluble DISC1 led to dysregulation of DISC1-PDE4 complexes, aberrantly increasing the activity of PDE4. Importantly, exogenous expression of a modified DISC1, which binds to PDE4 but not mutant HTT, normalized PDE4 activity and ameliorated anhedonia in the R6/2 mice. We propose that cross-seeding of mutant HTT and DISC1 and the resultant changes in PDE4 activity may underlie the pathology of a specific subset of mental manifestations of HD, which may provide an insight into molecular signaling in mental illness in general

Resümees der Magisterarbeiten 2001

植松健郎教授古稀・退職記念

Diet Quality and Its Relationship with Weight Characteristics in Pregnant Japanese Women: A Single-Center Birth Cohort Study

Maternal underweight and inadequate gestational weight gain (GWG) are problems in Japan. However, increases in food intake aimed at weight gain alone are not sufficient for mother–child health. This study assessed diet quality based on the 3-day dietary records of pregnant women in an urban area of Japan in order to show the importance of evaluating diet quality, using the Nutrient-Rich Food Index 9.3 (NRF9.3), which is one metric based on nutrition profiling, and the Japanese Food Guide Spinning Top (JFGST). After excluding misreporters of energy intake, we stratified women (n = 91) by pre-pregnancy body mass index (BMI) and determined energy intake, diet quality status, and their relationship with GWG. Intakes of carbohydrate-containing staple foods, vegetable dishes, and fruit were insufficient regardless of BMI. Most of the underweight women with inadequate GWG had insufficient energy intake but high diet quality, as assessed by NRF9.3. In contrast, most women who consumed energy within the recommended range had low diet quality and gained weight at inappropriate levels. These results highlight the importance for pregnant Japanese women to maintain diet quality through a nutrient-dense diet, while simultaneously increasing energy intake after evaluation of their individual diet quality