The self-diffusion coefficient, D, for pure liquid water has been measured at temperatures between 275.2 and 498.2 K and at pressures up to 1.75 kbart by the proton spin echo method. Our values of D agree, where they overlap, with recently published data which, however, were measured mostly at low temperature and over rather narrow ranges of temperature.The results are discussed in several ways. The Stokes-Einstein relation is found to be obeyed in the slipping boundary limit. The cubic cell model of Houghton accounts satisfactorily for the measured D values, particularly at higher temperatures. A simple test of a hard-sphere model i s found to give poor agreement at lower temperatures but a modified hard-sphere theory seems to be more satisfactory. The activation analysis at constant density shows that water behaves very differently from non-associated liquids. It also suggests that an increase in both temperature and pressure leads to an increase in the fraction of free unbonded water molecules.A free-volume analysis has led to a modified Arrhenius equation which involves pressure-dependent terms. This semi-empirical equation describes the results within experimental error and predicts a glass temperature at 115 K which is in reasonable agreement with the values obtained by other methods.There has recently been an increasing interest in the experimental determination of the self-diffusion coefficient, D, for compressed and heavy4 water at various temperatures. Measurements of D over a range of temperature and density will lead to a better understanding of both the diffusional behaviour of water imbedded in deep rocks and of some molecular transport properties of compressed heavy water such as the proton spin relaxation. However, all measurements of D for H 2 0 under pressure have so far been made1-3*5-9 at moderate temperatures only up to 332.2 K. A detailed discussion of previous self-diffusion measurements for compressed water was recently presented by Woolf2 and will not be repeated here. There also exist numerous measurements of D for liquid water under its saturated vapour pressure (s.v.P.)but only a few covered wide temperatureThe large spread of D values at 298.2 K in the earlier measurements was caused by systematic errors as discussed by Millsl3" and the best value13' is 2.299 xThe present study of self-diffusion in compressed pure water was undertaken to compare our D values measured by the proton spin echo method with those of tracer experiments by Woolf' at lower temperatures and to extend the experimental temperature range up to = 500 K. It seemed interesting to test the applicability of the StokesEinstein relations, the cubic cell rnodelI4 and the hard-sphere model over the widest temperature range. Finally, since the shear viscosity of water at S.V.P. could be represented by a modified Arrhenius equation,15 it was of interest to test the analogous equation for the self-diffusion of compressed water. m2 s-l. E X P E R I M E N T A LThe self-diffusion measurements were made by the n.m.r. spin echo m...

Epigenetic modifications are thought to be important for gene expression changes during development and aging. However, besides the Sir2 histone deacetylase in somatic tissues and H3K4 trimethylation in germlines, there is scant evidence implicating epigenetic regulations in aging. The insulin/IGF-1 signaling (IIS) pathway is a major life span regulatory pathway. Here, we show that progressive increases in gene expression and loss of H3K27me3 on IIS components are due, at least in part, to increased activity of the H3K27 demethylase UTX-1 during aging. RNAi of the utx-1 gene extended the mean life span of C. elegans by ~30%, dependent on DAF-16 activity and not additive in daf-2 mutants. The loss of utx-1 increased H3K27me3 on the Igf1r/daf-2 gene and decreased IIS activity, leading to a more "naive" epigenetic state. Like stem cell reprogramming, our results suggest that reestablishment of epigenetic marks lost during aging might help "reset" the developmental age of animal cells.

Spermatogenesis is a highly regulated process that produces sperm to transmit genetic information to the next generation. Although extensively studied in mice, our current understanding of primate spermatogenesis is limited to populations defined by state-specific markers defined from rodent data. As between-species differences have been reported in the process duration and cellular differentiation hierarchy, it remains unclear how molecular markers and cell states are conserved or have diverged from mice to man. To address this challenge, we employ single-cell RNA-sequencing to identify transcriptional signatures of major germ and somatic cell-types of the testes in human, macaque and mice. This approach reveals differences in expression throughout spermatogenesis, including the stem/progenitor pool of spermatogonia, classical markers of differentiation, potential regulators of meiosis, the kinetics of RNA turnover during spermatid differentiation, and germ cell-soma communication. These datasets provide a rich foundation for future targeted mechanistic studies of primate germ cell development and in vitro gametogenesis.

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Since at least the time of the Ancient Greeks, scholars have argued about whether the golden section-a number approximately equal to 0.618-holds the key to the secret of beauty. Empirical investigations of the aesthetic properties of the golden section date back to the very origins of scientific psychology itself, the first duties being conducted by Fechner in the 1860s. In this paper historical and contemporary issues are reviewed with regard to the alleged aesthetic properties of the golden section. In the introductory section the most important mathematical occurrences of the golden section are described. As well, brief reference is made to research on natural occurrences of the golden section, and to ancient and medieval knowledge and application of the golden section, primarily in art and architecture. Two major sections then discuss and critically examine empirical studies of the putative aesthetic properties of the golden section dating from the mid-19th century up to the 1950s, and the empirical work of the last three decades, respectively. It is concluded that there seems to be, in fact, real psychological effects associated with the golden section, but that they are relatively sensitive to careless methodological practices.

Identifying drug-drug interactions (DDIs) is a major challenge in drug development. Previous attempts have established formal approaches for pharmacokinetic (PK) DDIs, but there is not a feasible solution for pharmacodynamic (PD) DDIs because the endpoint is often a serious adverse event rather than a measurable change in drug concentration. Here, we developed a metric “S-score” that measures the strength of network connection between drug targets to predict PD DDIs. Utilizing known PD DDIs as golden standard positives (GSPs), we observed a significant correlation between S-score and the likelihood a PD DDI occurs. Our prediction was robust and surpassed existing methods as validated by two independent GSPs. Analysis of clinical side effect data suggested that the drugs having predicted DDIs have similar side effects. We further incorporated this clinical side effects evidence with S-score to increase the prediction specificity and sensitivity through a Bayesian probabilistic model. We have predicted 9,626 potential PD DDIs at the accuracy of 82% and the recall of 62%. Importantly, our algorithm provided opportunities for better understanding the potential molecular mechanisms or physiological effects underlying DDIs, as illustrated by the case studies.

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Dietary interventions are effective ways to extend or shorten lifespan. By examining midlife hepatic gene expressions in mice under different dietary conditions, which resulted in different lifespans and aging-related phenotypes, we were able to identify genes and pathways that modulate the aging process. We found that pathways transcriptionally correlated with diet-modulated lifespan and physiological changes were enriched for lifespanmodifying genes. Intriguingly, mitochondrial gene expression correlated with lifespan and anticorrelated with aging-related pathological changes, whereas peroxisomal gene expression showed an opposite trend. Both organelles produce reactive oxygen species, a proposed causative factor of aging. This finding implicates a contribution of peroxisome to aging. Consistent with this hypothesis, lowering the expression levels of peroxisome proliferation genes decreased the cellular peroxide levels and extended the lifespan of Drosophila melanogaster and Caenorhabditis elegans. These findings show that transcriptional changes resulting from dietary interventions can effectively reflect causal factors in aging and identify previously unknown or under-appreciated longevity pathways, such as the peroxisome pathway.systems biology | diet-induced obesity