Epigenetic modifications may play a role in the developmental consequences of early life events

Many aspects of postnatal development are influenced by events before birth, including cognitive and language development. An adverse intrauterine environment, for example secondary to poor maternal nutritional status, multiple pregnancy, or late preterm birth, is associated with increased risks of delayed or impaired childhood development and altered physiology in adulthood that may predispose to increased risk of adult disease. Maternal periconceptional undernutrition and twin conception can both result in late preterm birth, but it is less clear whether cases of late preterm birth not following a recognized early pregnancy event may still have their origin in the periconceptional period. Thus, the very earliest periods of pregnancy, and perhaps even the pre-pregnancy period, may be an important period determining the developmental trajectory of the fetus, and thus both pregnancy and later health outcomes. Profound epigenetic modifications to the genome occur in the early embryo as a normal part of development. Recent evidence suggests that environmental signals acting during early development may also result in epigenetic changes which may play a role in mediating the association between early life exposures and later phenotype

The mechanism of RNA base fraying: Molecular dynamics simulations analyzed with core-set Markov state models

The process of RNA base fraying (i.e. the transient opening of the termini of a helix) is involved in many aspects of RNA dynamics. We here use molecular dynamics simulations and Markov state models to characterize the kinetics of RNA fraying and its sequence and direction dependence. In particular, we first introduce a method for determining biomolecular dynamics employing core-set Markov state models constructed using an advanced clustering technique. The method is validated on previously reported simulations. We then use the method to analyze extensive trajectories for four different RNA model duplexes. Results obtained using D. E. Shaw research and AMBER force fields are compared and discussed in detail, and show a non-trivial interplay between the stability of intermediate states and the overall fraying kinetics

Sensitivity, Specificity and the Hybridization Isotherms of DNA Chips

Competitve hybridization, at the surface and in the bulk, lowers the sensitivity of DNA chips. Competitive surface hybridization occurs when different targets can hybridize with the same probe. Competitive bulk hybridization takes place when the targets can hybridize with free complementary chains in the solution. The effects of competitive hybridization on the thermodynamically attainable performance of DNA chips are quantified in terms of the hybridization isotherms of the spots. These relate the equilibrium degree of the hybridization to the bulk composition. The hybridization isotherm emerges as a Langmuir isotherm modified for electrostatic interactions within the probe layer. The sensitivity of the assay in equilibrium is directly related to the slope of the isotherm. A simpler description is possible in terms of $c_{50}$s specifying the bulk composition corresponding to 50% hybridization at the surface. The effects of competitive hybridization are important for the quantitative analysis of DNA chip results especially when used to study point mutations.Comment: 18 pages and 7 figures. To be published in Biophys.

Four governance reforms to strengthen the SDGs:A demanding policy vision can accelerate global sustainable development efforts

In 2015, the United Nations (UN) General Assembly agreed on 17 Sustainable Development Goals (SDGs) with 169 targets as part of the 2030 Agenda for Sustainable Development. Although the SDGs, which are to be achieved by 2030, are not the first attempt to guide policy actors through global goals, they go far beyond earlier agreements in their detail, comprehensiveness, and ambition. Yet the 2022 SDG Impact Assessment, conducted by a global consortium of researchers, has shown that the first phase of SDG implementation did not lead to a transformative reorientation of political systems and societies (1, 2). As the UN SDG Summit gets underway this month to review the halfway point in SDG implementation, and a further UN “Summit of the Future” is planned for 2024 to debate global governance reforms, we present here a demanding yet realistic policy vision to adjust the course of SDG implementation

The influence of weather regimes on European renewable energy production and demand

The growing share of variable renewable energy increases the meteorological sensitivity of power systems. This study investigates if large-scale weather regimes capture the influence of meteorological variability on the European energy sector. For each weather regime, the associated changes to wintertime -mean and extreme- wind and solar power production, temperature-driven energy demand and energy shortfall (residual load) are explored. Days with a blocked circulation pattern, i.e. the Scandinavian Blocking and NAO negative regimes, on average have lower than normal renewable power production, higher than normal energy demand and therefore, higher than normal energy shortfall. These average effects hide large variability of energy parameters within each weather regime. Though the risk of extreme high energy shortfall events increases in the two blocked regimes (by a factor of 2.0 and 1.5, respectively), it is shown that such events occur in all regimes. Extreme high energy shortfall events are the result of rare circulation types and smaller-scale features, rather than extreme magnitudes of common large-scale circulation types. In fact, these events resemble each other more strongly than their respective weather regime mean pattern. For (sub-)seasonal forecasting applications weather regimes may be of use for the energy sector. At shorter lead times or for more detailed system analyses, their ineffectiveness at characterising extreme events limits their potential

Periconceptional Undernutrition in Sheep Affects Adult Phenotype Only in Males

Periconceptional undernutrition (PCUN) in sheep alters fetal growth and metabolism and postnatal growth regulation, but effects on adult body composition are unknown. We investigated the effects of PCUN on adult phenotype. Singleton lambs of ewes fed normally (N, n=17) or undernourished before (UN-61-0 d, n=23), before and after (UN-61-30 d, n=19), or after (UN-2-30d, n=17) mating (d0) were weighed at birth, 12 weeks, and intermittently to adulthood. At the age of 3-4 years, body composition was assessed by dual-emission X-ray absorptiometry followed by postmortem examination. Compared with N animals, male, but not female, offspring of all UN groups had greater % fat mass (all UN versus N: 9±1 versus 2±1%, P<0.001) and perirenal fat (544±36 versus 222±44 g, P=0.002), and proportionately smaller hearts (4.5±0.1 versus 5.2±0.2 g·kg−1), lungs (9.1±0.2 versus 10.6±0.5 g·kg−1), and adrenals (0.06±0.002 versus 0.08±0.003 g·kg−1). UN males also had larger testes (726±21 versus 545±32 g, P=0.007), but UN females had smaller ovaries (2.7±0.08 versus 3.4±0.4 g, P=0.01). Changes were independent of birth weight or postnatal growth velocity. Brief PCUN has sex-specific effects on adult phenotype, predominantly affecting males, which may contribute to adverse metabolic outcomes

Associations between neonatal nutrition and visual outcomes in 7-year-old children born very preterm

PURPOSE: There is uncertainty about the effect of increased neonatal protein intake on neurodevelopmental outcomes following preterm birth. The aim of this study was to assess the effect of a change in neonatal nutrition protocol at a major tertiary neonatal intensive care unit intended to increase protein intake on ophthalmic and visual development in school-age children born very preterm.METHODS: The study cohort comprised children (n = 128) with birthweight &lt;1500 g or gestational age &lt; 30 weeks born at Auckland City Hospital before (OldPro group, n = 55) and after (NewPro group, n = 73) a reformulation of parenteral nutrition that resulted in increased total protein intake during the first postnatal week and decreased carbohydrate, total parenteral fluid and sodium intake. Clinical and psychophysical vision assessments were completed at 7 years' corrected age, including visual acuity, global motion perception (a measure of dorsal stream function), stereoacuity, ocular motility and ocular health. Composite measures of favourable overall visual, binocular and functional visual outcomes along with individual vision measures were compared between the groups using logistic and linear regression models.RESULTS: Favourable overall visual outcome did not differ between the two groups. However, global motion perception was better in the NewPro group (p = 0.04), whereas the OldPro group were more likely to have favourable binocular visual outcomes (60% vs. 36%, p = 0.02) and passing stereoacuity (p = 0.02).CONCLUSIONS: These results indicate subtle but complex associations between early neonatal nutrition after very preterm birth and visual development at school age.</p

Whole animal experiments should be more like human randomized controlled trials

Beverly S. Muhlhausler, Frank H. Bloomfield, Matthew W. Gillma