Patient satisfaction with oral health check-ups at a community pharmacy and their effect on oral self-care habits and dental consultation behavior.

Maintaining good oral health is important because oral diseases are related to systemic diseases, and community pharmacies play a key role in maintaining the health of local residents. This study aimed to examine the effects of oral health check-ups and information provision at community pharmacies on oral health-associated behaviors as well as patient satisfaction. We conducted oral health check-ups and provided information about oral health self-care to 84 patients at a community pharmacy, and then asked them to complete a questionnaire survey. One month later, we sent them a follow-up questionnaire and received responses from 66.7% (56/84) of the participants. The large majority were satisfied with the salivary test (95.2%) and the information (96.4%) we provided. Most of the participants (89.3%) indicated that they wanted to use the oral health check-up service again in the future. Compared with baseline, the ratio of participants restricting their intake of sugar-rich foods and drinks significantly increased 1 month later (p = 0.021). About 60% of those who had not undergone a regular dental examination at baseline reported newly visiting or planning to visit a dental clinic. The results revealed high satisfaction with the oral health check-up and information about oral self-care they received at the community pharmacy. The results suggested that oral health check-ups had the potential to change both oral self-care habits and dental consultation behavior. Our findings indicate that community pharmacies can contribute to the maintenance and promotion of oral health by providing oral health check-ups to local residents.

Cell dormancy plasticity: quiescence deepens into senescence through a dimmer switch.

Both being dormant cellular states, quiescence and senescence are traditionally considered distinct. Quiescence is reversible to proliferation upon growth signals, whereas senescence is irreversible in physiological conditions. Recent findings, however, suggest that quiescence deepening with a decreased proliferative tendency, but not capability, is a common transition path toward senescence in many cell and tissue types. This transition is associated with the continuously increased activation threshold of an RB-E2F-CDK gene network switch.

The InsP7 phosphatase Siw14 regulates inositol pyrophosphate levels to control localization of the general stress response transcription factor Msn2.

The environmental stress response (ESR) is critical for cell survival. Yeast cells unable to synthesize inositol pyrophosphates (PP-InsPs) are unable to induce the ESR. We recently discovered a diphosphoinositol pentakisphosphate (PP-InsP5) phosphatase in Saccharomyces cerevisiae encoded by SIW14 Yeast strains deleted for SIW14 have increased levels of PP-InsPs. We hypothesized that strains with high inositol pyrophosphate levels will have an increased stress response. We examined the response of the siw14Δ mutant to heat shock, nutrient limitation, osmotic stress, and oxidative treatment using cell growth assays and found increased resistance to each. Transcriptional responses to oxidative and osmotic stresses were assessed using microarray and reverse transcriptase quantitative PCR. The ESR was partially induced in the siw14Δ mutant strain, consistent with the increased stress resistance, and the mutant strain further induced the ESR in response to oxidative and osmotic stresses. The levels of PP-InsPs increased in WT cells under oxidative stress but not under hyperosmotic stress, and they were high and unchanging in the mutant. Phosphatase activity of Siw14 was inhibited by oxidation that was reversible. To determine how altered PP-InsP levels affect the ESR, we performed epistasis experiments with mutations in rpd3 and msn2/4 combined with siw14Δ. We show that mutations in msn2Δ and msn4Δ, but not rpd3, are epistatic to siw14Δ by assessing growth under oxidative stress conditions and expression of CTT1 Msn2-GFP nuclear localization was increased in the siw14Δ. These data support a model in which the modulation of PP-InsPs influence the ESR through general stress response transcription factors Msn2/4.

Graded regulation of cellular quiescence depth between proliferation and senescence by a lysosomal dimmer switch.

The reactivation of quiescent cells to proliferate is fundamental to tissue repair and homeostasis in the body. Often referred to as the G0 state, quiescence is, however, not a uniform state but with graded depth. Shallow quiescent cells exhibit a higher tendency to revert to proliferation than deep quiescent cells, while deep quiescent cells are still fully reversible under physiological conditions, distinct from senescent cells. Cellular mechanisms underlying the control of quiescence depth and the connection between quiescence and senescence are poorly characterized, representing a missing link in our understanding of tissue homeostasis and regeneration. Here we measured transcriptome changes as rat embryonic fibroblasts moved from shallow to deep quiescence over time in the absence of growth signals. We found that lysosomal gene expression was significantly up-regulated in deep quiescence, and partially compensated for gradually reduced autophagy flux. Reducing lysosomal function drove cells progressively deeper into quiescence and eventually into a senescence-like irreversibly arrested state; increasing lysosomal function, by lowering oxidative stress, progressively pushed cells into shallower quiescence. That is, lysosomal function modulates graded quiescence depth between proliferation and senescence as a dimmer switch. Finally, we found that a gene-expression signature developed by comparing deep and shallow quiescence in fibroblasts can correctly classify a wide array of senescent and aging cell types in vitro and in vivo, suggesting that while quiescence is generally considered to protect cells from irreversible arrest of senescence, quiescence deepening likely represents a common transition path from cell proliferation to senescence, related to aging.

Crack the state of silence: Tune the depth of cellular quiescence for cancer therapy.

The regulation of cellular quiescence underlies numerous physiopathological phenomena. We recently found that quiescence depth can be tuned as to adjust a dimmer switch, by altering the expression of genes in the Retinoblastoma (Rb)-E2f pathway. Reducing quiescence depth may wake dormant cancer cells and make them susceptible to treatment.

Exit from quiescence displays a memory of cell growth and division.

Reactivating quiescent cells to proliferate is critical to tissue repair and homoeostasis. Quiescence exit is highly noisy even for genetically identical cells under the same environmental conditions. Deregulation of quiescence exit is associated with many diseases, but cellular mechanisms underlying the noisy process of exiting quiescence are poorly understood. Here we show that the heterogeneity of quiescence exit reflects a memory of preceding cell growth at quiescence induction and immediate division history before quiescence entry, and that such a memory is reflected in cell size at a coarse scale. The deterministic memory effects of preceding cell cycle, coupled with the stochastic dynamics of an Rb-E2F bistable switch, jointly and quantitatively explain quiescence-exit heterogeneity. As such, quiescence can be defined as a distinct state outside of the cell cycle while displaying a sequential cell order reflecting preceding cell growth and division variations.The quiescence-exit process is noisy even in genetically identical cells under the same environmental conditions. Here the authors show that the heterogeneity of quiescence exit reflects a memory of preceding cell growth at quiescence induction and immediate division history prior to quiescence entry.

Cutting Edge: AhR Is a Molecular Target of Calcitriol in Human T Cells.

The immunoregulatory functions of vitamin D have been well documented in various immunological disorders, including multiple sclerosis, arthritis, and asthma. IL-10 is considered a chief effector molecule that promotes the vitamin D-induced immunosuppressive states of T cells and accessory cells. In this article, we demonstrate that the active form of vitamin D, 1,25-dihydroxyvitamin D3 (calcitriol), has a profound inhibitory effect on the development of human Th9, a CD4 T cell subset that is highly associated with asthma, in an IL-10-independent manner. Our data show that calcitriol represses the expression of BATF, a transcription factor essential for Th9, via suppressing the expression of aryl hydrocarbon receptor, without an increase in IL-10. The data show a novel link between vitamin D and two key transcription factors involved in T cell differentiation.

Comparative transcriptomic analysis of two closely related ground beetle species with marked genital divergence using pyrosequencing.

Ground beetles of the subgenus Ohomopterus (genus Carabus) show marked divergence in species-specific male and female genital morphologies, which contributes to reproductive isolation among species. Characterizing the genetic basis of species-specific genital morphology is essential for understanding their diversification, but genomic information on Ohomopterus is not yet available. We analyzed mRNA extracted from abdominal sections of the last instar larvae and pupae of two sister species, Carabus (Ohomopterus) iwawakianus and C. (O.) uenoi, which show marked differences in genital morphology, to compare transcriptomic profiles using Roche 454 pyrosequencing. We obtained 1,608,572 high-quality reads and assembled them into 176,278 unique sequences, of which 66,049 sequences were combined into 12,662 clusters. Differential expression analyses for sexed pupae suggested that four and five clusters were differentially expressed between species for males and females, respectively. We also identified orthologous sequences of genes involved in genital development in Drosophila, which potentially affect genital development and species-specific genital morphology in Ohomopterus. This study provides the first large transcriptomic data set for a morphologically diversified beetle group, which can facilitate future studies on the genetic basis of species-specific genitalia.

Transcriptome dynamics in early embryos of the ascidian, Ciona intestinalis.

Maternally provided mRNAs and proteins direct early development and activate the zygotic genome. Using microarrays, we examined the dynamics of transcriptomes during the early development of a basal chordate, Ciona intestinalis. Microarray analysis of unfertilized eggs, as well as 8-, and 16- and 32-cell embryos revealed that nearly half of the genes encoded in the genome were expressed maternally, and that approximately only one-fourth of these genes were expressed at similar levels among eggs obtained from different individuals. Genes encoding proteins involved in protein phosphorylation were enriched in this latter group. More than 90% of maternal RNAs were not reduced before the 16-cell stage when the zygotic developmental program begins. Additionally we obtained gene expression profiles of individual blastomeres from the 8- and 16-cell embryos. On the basis of these profiles, we concluded that the posterior-most localization, which has been reported for over 20 different transcripts, is the only major localization pattern of maternal transcripts. Our data also showed that maternal factors establish only nine distinct patterns of zygotic gene expression at the 16-cell stage. Therefore, one of the main developmental functions of maternally supplied information is to establish these nine distinct expression patterns in the 16-cell embryo. The dynamics of transcriptomes in early-stage embryos provides a foundation for studying how maternal information starts the zygotic program.