Low resting metabolic rate and increased hunger due to ß-MSH and ß-endorphin deletion in a canine model.

Mutations that perturb leptin-melanocortin signaling are known to cause hyperphagia and obesity, but energy expenditure has not been well studied outside rodents. We report on a common canine mutation in pro-opiomelanocortin (POMC), which prevents production of ß-melanocyte-stimulating hormone (ß-MSH) and ß-endorphin but not α-MSH; humans, similar to dogs, produce α-MSH and ß-MSH from the POMC propeptide, but rodents produce only α-MSH. We show that energy expenditure is markedly lower in affected dogs, which also have increased motivational salience in response to a food cue, indicating increased wanting or hunger. There was no difference in satiety at a modified ad libitum meal or in their hedonic response to food, nor disruption of adrenocorticotropic hormone (ACTH) or thyroid axes. In vitro, we show that ß-MSH signals comparably to α-MSH at melanocortin receptors. These data implicate ß-MSH and ß-endorphin as important in determining hunger and moderating energy expenditure and suggest that this role is independent of the presence of α-MSH.

Epigenome-wide association study of dietary fatty acid intake.

BACKGROUND: Dietary intake of n-3 polyunsaturated fatty acids (PUFA) may have a protective effect on the development of cardiovascular diseases, diabetes, depression and cancer, while a high intake of n-6 PUFA was often reported to be associated with inflammation-related traits. The effect of PUFAs on health outcomes might be mediated by DNA methylation (DNAm). The aim of our study is to identify the impact of PUFA intake on DNAm in the Cooperative Health Research in the Region of Augsburg (KORA) FF4 cohort and the Leiden Longevity Study (LLS). RESULTS: DNA methylation levels were measured in whole blood from the population-based KORA FF4 study (N = 1354) and LLS (N = 448), using the Illumina MethylationEPIC BeadChip and Illumina HumanMethylation450 array, respectively. We assessed associations between DNAm and intake of eight and four PUFAs in KORA and LLS, respectively. Where possible, results were meta-analyzed. Below the Bonferroni correction threshold (p < 7.17 × 10-8), we identified two differentially methylated positions (DMPs) associated with PUFA intake in the KORA study. The DMP cg19937480, annotated to gene PRDX1, was positively associated with docosahexaenoic acid (DHA) in model 1 (beta: 2.00 × 10-5, 95%CI: 1.28 × 10-5-2.73 × 10-5, P value: 6.98 × 10-8), while cg05041783, annotated to gene MARK2, was positively associated with docosapentaenoic acid (DPA) in our fully adjusted model (beta: 9.80 × 10-5, 95%CI: 6.25 × 10-5-1.33 × 10-4, P value: 6.75 × 10-8). In the meta-analysis, we identified the CpG site (cg15951061), annotated to gene CDCA7L below Bonferroni correction (1.23 × 10-7) associated with eicosapentaenoic acid (EPA) intake in model 1 (beta: 2.00 × 10-5, 95% CI: 1.27 × 10-5-2.73 × 10-5, P value = 5.99 × 10-8) and we confirmed the association of cg19937480 with DHA in both models 1 and 2 (beta: 2.07 × 10-5, 95% CI: 1.31 × 10-5-2.83 × 10-5, P value = 1.00 × 10-7 and beta: 2.19 × 10-5, 95% CI: 1.41 × 10-5-2.97 × 10-5, P value = 5.91 × 10-8 respectively). CONCLUSIONS: Our study identified three CpG sites associated with PUFA intake. The mechanisms of these sites remain largely unexplored, highlighting the novelty of our findings. Further research is essential to understand the links between CpG site methylation and PUFA outcomes.

Effects of Repeated Freeze and Thaw Cycles on the Genome-Wide DNA Methylation Profile of Isolated Genomic DNA.

The characterization of DNA methylation patterns to identify epigenetic markers for complex human diseases is an important and rapidly evolving part in biomedical research. DNA samples collected and stored in clinical biobanks over the past years are an important source for future epigenetic studies. Isolated gDNA is considered stable when stored at low temperatures for several years. However, the effect of multiple use and the associated repeated thawing of long-term stored DNA samples on DNA methylation patterns has not yet been investigated. In this study, we examined the influence of up to 10 freeze and thaw cycles on global DNA methylation by comparing genome-wide methylation profiles. DNA samples from 19 healthy volunteers were either frozen at -80°C or subjected to up to 10 freeze and thaw cycles. Genome-wide DNA methylation was analyzed after 0, 1, 3, 5, or 10 thaw cycles using the Illumina Infinium MethylationEPIC BeadChip. Evaluation of the global DNA methylation profile by beta-value density plots and multidimensional scaling plots revealed an expected clear participant-dependent variability, but a very low variability depending on the freeze and thaw cycles. In accordance, no significant difference in any of the methylated cytosine/guanine sites studied could be detected in the performed statistical analyses. Our results suggest that long-term frozen DNA samples are still suitable for epigenetic studies after multiple thaw cycles.

Examination of head versus body heading may help clarify the extent to which animal movement pathways are structured by environmental cues?

Understanding the processes that determine how animals allocate time to space is a major challenge, although it is acknowledged that summed animal movement pathways over time must define space-time use. The critical question is then, what processes structure these pathways? Following the idea that turns within pathways might be based on environmentally determined decisions, we equipped Arabian oryx with head- and body-mounted tags to determine how they orientated their heads - which we posit is indicative of them assessing the environment - in relation to their movement paths, to investigate the role of environment scanning in path tortuosity. After simulating predators to verify that oryx look directly at objects of interest, we recorded that, during routine movement, > 60% of all turns in the animals' paths, before being executed, were preceded by a change in head heading that was not immediately mirrored by the body heading: The path turn angle (as indicated by the body heading) correlated with a prior change in head heading (with head heading being mirrored by subsequent turns in the path) twenty-one times more than when path turns occurred due to the animals adopting a body heading that went in the opposite direction to the change in head heading. Although we could not determine what the objects of interest were, and therefore the proposed reasons for turning, we suggest that this reflects the use of cephalic senses to detect advantageous environmental features (e.g. food) or to detect detrimental features (e.g. predators). The results of our pilot study suggest how turns might emerge in animal pathways and we propose that examination of points of inflection in highly resolved animal paths could represent decisions in landscapes and their examination could enhance our understanding of how animal pathways are structured.

Metabolomic biomarkers of habitual B vitamin intakes unveil novel differentially methylated positions in the human epigenome.

BACKGROUND: B vitamins such as folate (B9), B6, and B12 are key in one carbon metabolism, which generates methyl donors for DNA methylation. Several studies have linked differential methylation to self-reported intakes of folate and B12, but these estimates can be imprecise, while metabolomic biomarkers can offer an objective assessment of dietary intakes. We explored blood metabolomic biomarkers of folate and vitamins B6 and B12, to carry out epigenome-wide analyses across up to three European cohorts. Associations between self-reported habitual daily B vitamin intakes and 756 metabolites (Metabolon Inc.) were assessed in serum samples from 1064 UK participants from the TwinsUK cohort. The identified B vitamin metabolomic biomarkers were then used in epigenome-wide association tests with fasting blood DNA methylation levels at 430,768 sites from the Infinium HumanMethylation450 BeadChip in blood samples from 2182 European participants from the TwinsUK and KORA cohorts. Candidate signals were explored for metabolite associations with gene expression levels in a subset of the TwinsUK sample (n = 297). Metabolomic biomarker epigenetic associations were also compared with epigenetic associations of self-reported habitual B vitamin intakes in samples from 2294 European participants. RESULTS: Eighteen metabolites were associated with B vitamin intakes after correction for multiple testing (Bonferroni-adj. p < 0.05), of which 7 metabolites were available in both cohorts and tested for epigenome-wide association. Three metabolites - pipecolate (metabolomic biomarker of B6 and folate intakes), pyridoxate (marker of B6 and folate) and docosahexaenoate (DHA, marker of B6) - were associated with 10, 3 and 1 differentially methylated positions (DMPs), respectively. The strongest association was observed between DHA and DMP cg03440556 in the SCD gene (effect = 0.093 ± 0.016, p = 4.07E-09). Pyridoxate, a catabolic product of vitamin B6, was inversely associated with CpG methylation near the SLC1A5 gene promoter region (cg02711608 and cg22304262) and with SLC7A11 (cg06690548), but not with corresponding changes in gene expression levels. The self-reported intake of folate and vitamin B6 had consistent but non-significant associations with the epigenetic signals. CONCLUSION: Metabolomic biomarkers are a valuable approach to investigate the effects of dietary B vitamin intake on the human epigenome.

Associations between medium- and long-term exposure to air temperature and epigenetic age acceleration.

Climate change poses a serious threat to human health worldwide, while aging populations increase. However, no study has ever investigated the effects of air temperature on epigenetic age acceleration. This study involved 1,725 and 1,877 participants from the population-based KORA F4 (2006-2008) and follow-up FF4 (2013-2014) studies, respectively, conducted in Augsburg, Germany. The difference between epigenetic age and chronological age was referred to as epigenetic age acceleration and reflected by Horvath's epigenetic age acceleration (HorvathAA), Hannum's epigenetic age acceleration (HannumAA), PhenoAge acceleration (PhenoAA), GrimAge acceleration (GrimAA), and Epigenetic Skin and Blood Age acceleration (SkinBloodAA). Daily air temperature was estimated using hybrid spatiotemporal regression-based models. To explore the medium- and long-term effects of air temperature modeled in time and space on epigenetic age acceleration, we applied generalized estimating equations (GEE) with distributed lag non-linear models, and GEE, respectively. We found that high temperature exposure based on the 8-week moving average air temperature (97.5th percentile of temperature compared to median temperature) was associated with increased HorvathAA, HannumAA, GrimAA, and SkinBloodAA: 1.83 (95% CI: 0.29-3.37), 11.71 (95% CI: 8.91-14.50), 2.26 (95% CI: 1.03-3.50), and 5.02 (95% CI: 3.42-6.63) years, respectively. Additionally, we found consistent results with high temperature exposure based on the 4-week moving average air temperature was associated with increased HannumAA, GrimAA, and SkinBloodAA: 9.18 (95% CI: 6.60-11.76), 1.78 (95% CI: 0.66-2.90), and 4.07 (95% CI: 2.56-5.57) years, respectively. For the spatial variation in annual average temperature, a 1 °C increase was associated with an increase in all five measures of epigenetic age acceleration (HorvathAA: 0.41 [95% CI: 0.24-0.57], HannumAA: 2.24 [95% CI: 1.95-2.53], PhenoAA: 0.32 [95% CI: 0.05-0.60], GrimAA: 0.24 [95%: 0.11-0.37], and SkinBloodAA: 1.17 [95% CI: 1.00-1.35] years). In conclusion, our results provide first evidence that medium- and long-term exposures to high air temperature affect increases in epigenetic age acceleration.

The behaviour and activity budgets of two sympatric sloths; Bradypus variegatus and Choloepus hoffmanni.

It is usually beneficial for species to restrict activity to a particular phase of the 24-hour cycle as this enables the development of morphological and behavioural adaptations to enhance survival under specific biotic and abiotic conditions. Sloth activity patterns are thought to be strongly related to the environmental conditions due to the metabolic consequences of having a low and highly variable core body temperature. Understanding the drivers of sloth activity and their ability to withstand environmental fluctuations is of growing importance for the development of effective conservation measures, particularly when we consider the vulnerability of tropical ecosystems to climate change and the escalating impacts of anthropogenic activities in South and Central America. Unfortunately, the cryptic nature of sloths makes long term observational research difficult and so there is very little existing literature examining the behavioural ecology of wild sloths. Here, we used micro data loggers to continuously record, for the first time, the behaviour of both Bradypus and Choloepus sloths over periods of days to weeks. We investigate how fluctuations in the environmental conditions affect the activity of sloths inhabiting a lowland rainforest on the Caribbean coast of Costa Rica and examined how this might relate to their low power lifestyle. Both Bradypus and Choloepus sloths were found to be cathemeral in their activity, with high levels of between-individual and within-individual variation in the amounts of time spent active, and in the temporal distribution of activity over the 24-hour cycle. Daily temperature did not affect activity, although Bradypus sloths were found to show increased nocturnal activity on colder nights, and on nights following colder days. Our results demonstrate a distinct lack of synchronicity within the same population, and we suggest that this pattern provides sloths with the flexibility to exploit favourable environmental conditions whilst reducing the threat of predation.

Wearable sensors for monitoring marine environments and their inhabitants.

Human societies depend on marine ecosystems, but their degradation continues. Toward mitigating this decline, new and more effective ways to precisely measure the status and condition of marine environments are needed alongside existing rebuilding strategies. Here, we provide an overview of how sensors and wearable technology developed for humans could be adapted to improve marine monitoring. We describe barriers that have slowed the transition of this technology from land to sea, update on the developments in sensors to advance ocean observation and advocate for more widespread use of wearables on marine organisms in the wild and in aquaculture. We propose that large-scale use of wearables could facilitate the concept of an 'internet of marine life' that might contribute to a more robust and effective observation system for the oceans and commercial aquaculture operations. These observations may aid in rationalizing strategies toward conservation and restoration of marine communities and habitats.

Dietary and supplemental intake of vitamins C and E is associated with altered DNA methylation in an epigenome-wide association study meta-analysis.

BACKGROUND: Dietary intake of antioxidants such as vitamins C and E protect against oxidative stress, and may also be associated with altered DNA methylation patterns. METHODS: We meta-analysed epigenome-wide association study (EWAS) results from 11,866 participants across eight population-based cohorts to evaluate the association between self-reported dietary and supplemental intake of vitamins C and E with DNA methylation. EWAS were adjusted for age, sex, BMI, caloric intake, blood cell type proportion, smoking status, alcohol consumption, and technical covariates. Significant results of the meta-analysis were subsequently evaluated in gene set enrichment analysis (GSEA) and expression quantitative trait methylation (eQTM) analysis. RESULTS: In meta-analysis, methylation at 4,656 CpG sites was significantly associated with vitamin C intake at FDR ≤ 0.05. The most significant CpG sites associated with vitamin C (at FDR ≤ 0.01) were enriched for pathways associated with systems development and cell signalling in GSEA, and were associated with downstream expression of genes enriched in the immune response in eQTM analysis. Furthermore, methylation at 160 CpG sites was significantly associated with vitamin E intake at FDR ≤ 0.05, but GSEA and eQTM analysis of the top most significant CpG sites associated with vitamin E did not identify significant enrichment of any biological pathways investigated. CONCLUSIONS: We identified significant associations of many CpG sites with vitamin C and E intake, and our results suggest that vitamin C intake may be associated with systems development and the immune response.

Impact of test, vaccinate or remove protocol on home ranges and nightly movements of badgers a medium density population.

In the British Isles, the European badger (Meles meles) is thought to be the primary wildlife reservoir of bovine tuberculosis (bTB), an endemic disease in cattle. Test, vaccinate or remove ('TVR') of bTB test-positive badgers, has been suggested to be a potentially useful protocol to reduce bTB incidence in cattle. However, the practice of removing or culling badgers is controversial both for ethical reasons and because there is no consistent observed effect on bTB levels in cattle. While removing badgers reduces population density, it may also result in disruption of their social behaviour, increase their ranging, and lead to greater intra- and inter-species bTB transmission. This effect has been recorded in high badger density areas, such as in southwest England. However, little is known about how TVR affects the behaviour and movement of badgers within a medium density population, such as those that occur in Northern Ireland (NI), which the current study aimed to examine. During 2014-2017, badger ranging behaviours were examined prior to and during a TVR protocol in NI. Nightly distances travelled by 38 individuals were determined using Global Positioning System (GPS) measurements of animal tracks and GPS-enhanced dead-reckoned tracks. The latter was calculated using GPS, tri-axial accelerometer and tri-axial magnetometer data loggers attached to animals. Home range and core home range size were measured using 95% and 50% autocorrelated kernel density estimates, respectively, based on location fixes. TVR was not associated with measured increases in either distances travelled per night (mean = 3.31 ± 2.64 km) or home range size (95% mean = 1.56 ± 0.62 km2, 50% mean = 0.39 ± 0.62 km2) over the four years of study. However, following trapping, mean distances travelled per night increased by up to 44% eight days post capture. Findings differ from those observed in higher density badger populations in England, in which badger ranging increased following culling. Whilst we did not assess behaviours of individual badgers, possible reasons why no differences in home range size were observed include higher inherent 'social fluidity' in Irish populations whereby movements are less restricted by habitat saturation and/or that the numbers removed did not reach a threshold that might induce increases in ranging behaviour. Nevertheless, short-term behavioural disruption from trapping was observed, which led to significant increases in the movements of individual animals within their home range. Whether or not TVR may alter badger behaviours remains to be seen, but it would be better to utilise solutions such as oral vaccination of badgers and/or cattle as well as increased biosecurity to limit bTB transmission, which may be less likely to cause interference and thereby reduce the likelihood of bTB transmission.

Pooled analysis of epigenome-wide association studies of food consumption in KORA, TwinsUK and LLS.

PURPOSE: Examining epigenetic patterns is a crucial step in identifying molecular changes of disease pathophysiology, with DNA methylation as the most accessible epigenetic measure. Diet is suggested to affect metabolism and health via epigenetic modifications. Thus, our aim was to explore the association between food consumption and DNA methylation. METHODS: Epigenome-wide association studies were conducted in three cohorts: KORA FF4, TwinsUK, and Leiden Longevity Study, and 37 dietary exposures were evaluated. Food group definition was harmonized across the three cohorts. DNA methylation was measured using Infinium MethylationEPIC BeadChip in KORA and Infinium HumanMethylation450 BeadChip in the Leiden study and the TwinsUK study. Overall, data from 2293 middle-aged men and women were included. A fixed-effects meta-analysis pooled study-specific estimates. The significance threshold was set at 0.05 for false-discovery rate-adjusted p values per food group. RESULTS: We identified significant associations between the methylation level of CpG sites and the consumption of onions and garlic (2), nuts and seeds (18), milk (1), cream (11), plant oils (4), butter (13), and alcoholic beverages (27). The signals targeted genes of metabolic health relevance, for example, GLI1, RPTOR, and DIO1, among others. CONCLUSION: This EWAS is unique with its focus on food groups that are part of a Western diet. Significant findings were mostly related to food groups with a high-fat content.

Highlighting when animals expend excessive energy for travel using dynamic body acceleration.

Travel represents a major cost for many animals so there should be selection pressure for it to be efficient - at minimum cost. However, animals sometimes exceed minimum travel costs for reasons that must be correspondingly important. We use Dynamic Body Acceleration (DBA), an acceleration-based metric, as a proxy for movement-based power, in tandem with vertical velocity (rate of change in depth) in a shark (Rhincodon typus) to derive the minimum estimated power required to swim at defined vertical velocities. We show how subtraction of measured DBA from the estimated minimum power for any given vertical velocity provides a "proxy for power above minimum" metric (PPAmin), highlighting when these animals travel above minimum power. We suggest that the adoption of this metric across species has value in identifying where and when animals are subject to compelling conditions that lead them to deviate from ostensibly judicious energy expenditure.

Wake respirometry allows breath-by-breath assessment of ventilation and CO2 production in unrestrained animals.

Quantifying stress and energetic responses in animals are major challenges, as existing methods lack temporal resolution and elevate animal stress. We propose "wake respirometry," a new method of quantifying fine-scale changes in CO2 production in unrestrained animals, using a nondispersive infrared CO2 sensor positioned downwind of the animal, i.e., in its wake. We parameterize the dispersion of CO2 in wakes using known CO2 flow rates and wind speeds. Tests with three bird species in a wind tunnel demonstrated that the system can resolve breath-by-breath changes in CO2 concentration, with clear exhalation signatures increasing in period and integral with body size. Changes in physiological state were detectable following handling, flight, and exposure to a perceived threat. We discuss the potential of wake respirometry to quantify stress and respiratory patterns in wild animals and provide suggestions for estimating behavior-specific metabolic rates via full integration of CO2 production across the wake.

Ecological inference using data from accelerometers needs careful protocols.

Accelerometers in animal-attached tags are powerful tools in behavioural ecology, they can be used to determine behaviour and provide proxies for movement-based energy expenditure. Researchers are collecting and archiving data across systems, seasons and device types. However, using data repositories to draw ecological inference requires a good understanding of the error introduced according to sensor type and position on the study animal and protocols for error assessment and minimisation.Using laboratory trials, we examine the absolute accuracy of tri-axial accelerometers and determine how inaccuracies impact measurements of dynamic body acceleration (DBA), a proxy for energy expenditure, in human participants. We then examine how tag type and placement affect the acceleration signal in birds, using pigeons Columba livia flying in a wind tunnel, with tags mounted simultaneously in two positions, and back- and tail-mounted tags deployed on wild kittiwakes Rissa tridactyla. Finally, we present a case study where two generations of tag were deployed using different attachment procedures on red-tailed tropicbirds Phaethon rubricauda foraging in different seasons.Bench tests showed that individual acceleration axes required a two-level correction to eliminate measurement error. This resulted in DBA differences of up to 5% between calibrated and uncalibrated tags for humans walking at a range of speeds. Device position was associated with greater variation in DBA, with upper and lower back-mounted tags varying by 9% in pigeons, and tail- and back-mounted tags varying by 13% in kittiwakes. The tropicbird study highlighted the difficulties of attributing changes in signal amplitude to a single factor when confounding influences tend to covary, as DBA varied by 25% between seasons.Accelerometer accuracy, tag placement and attachment critically affect the signal amplitude and thereby the ability of the system to detect biologically meaningful phenomena. We propose a simple method to calibrate accelerometers that can be executed under field conditions. This should be used prior to deployments and archived with resulting data. We also suggest a way that researchers can assess accuracy in previously collected data, and caution that variable tag placement and attachment can increase sensor noise and even generate trends that have no biological meaning.

The extinct shark Otodus megalodon was a transoceanic superpredator: Inferences from 3D modeling.

Although shark teeth are abundant in the fossil record, their bodies are rarely preserved. Thus, our understanding of the anatomy of the extinct Otodus megalodon remains rudimentary. We used an exceptionally well-preserved fossil to create the first three-dimensional model of the body of this giant shark and used it to infer its movement and feeding ecology. We estimate that an adult O. megalodon could cruise at faster absolute speeds than any shark species today and fully consume prey the size of modern apex predators. A dietary preference for large prey potentially enabled O. megalodon to minimize competition and provided a constant source of energy to fuel prolonged migrations without further feeding. Together, our results suggest that O. megalodon played an important ecological role as a transoceanic superpredator. Hence, its extinction likely had large impacts on global nutrient transfer and trophic food webs.

Association between Usual Dietary Intake of Food Groups and DNA Methylation and Effect Modification by Metabotype in the KORA FF4 Cohort.

Associations between diet and DNA methylation may vary among subjects with different metabolic states, which can be captured by clustering populations in metabolically homogenous subgroups, called metabotypes. Our aim was to examine the relationship between habitual consumption of various food groups and DNA methylation as well as to test for effect modification by metabotype. A cross-sectional analysis of participants (median age 58 years) of the population-based prospective KORA FF4 study, habitual dietary intake was modeled based on repeated 24-h diet recalls and a food frequency questionnaire. DNA methylation was measured using the Infinium MethylationEPIC BeadChip providing data on >850,000 sites in this epigenome-wide association study (EWAS). Three metabotype clusters were identified using four standard clinical parameters and BMI. Regression models were used to associate diet and DNA methylation, and to test for effect modification. Few significant signals were identified in the basic analysis while many significant signals were observed in models including food group-metabotype interaction terms. Most findings refer to interactions of food intake with metabotype 3, which is the metabotype with the most unfavorable metabolic profile. This research highlights the importance of the metabolic characteristics of subjects when identifying associations between diet and white blood cell DNA methylation in EWAS.

Longitudinal associations of DNA methylation and sleep in children: a meta-analysis.

BACKGROUND: Sleep is important for healthy functioning in children. Numerous genetic and environmental factors, from conception onwards, may influence this phenotype. Epigenetic mechanisms such as DNA methylation have been proposed to underlie variation in sleep or may be an early-life marker of sleep disturbances. We examined if DNA methylation at birth or in school age is associated with parent-reported and actigraphy-estimated sleep outcomes in children. METHODS: We meta-analysed epigenome-wide association study results. DNA methylation was measured from cord blood at birth in 11 cohorts and from peripheral blood in children (4-13 years) in 8 cohorts. Outcomes included parent-reported sleep duration, sleep initiation and fragmentation problems, and actigraphy-estimated sleep duration, sleep onset latency and wake-after-sleep-onset duration. RESULTS: We found no associations between DNA methylation at birth and parent-reported sleep duration (n = 3658), initiation problems (n = 2504), or fragmentation (n = 1681) (p values above cut-off 4.0 × 10-8). Lower methylation at cg24815001 and cg02753354 at birth was associated with longer actigraphy-estimated sleep duration (p = 3.31 × 10-8, n = 577) and sleep onset latency (p = 8.8 × 10-9, n = 580), respectively. DNA methylation in childhood was not cross-sectionally associated with any sleep outcomes (n = 716-2539). CONCLUSION: DNA methylation, at birth or in childhood, was not associated with parent-reported sleep. Associations observed with objectively measured sleep outcomes could be studied further if additional data sets become available.

Maternal-fetal stress and DNA methylation signatures in neonatal saliva: an epigenome-wide association study.

BACKGROUND: Maternal stress before, during and after pregnancy has profound effects on the development and lifelong function of the infant's neurocognitive development. We hypothesized that the programming of the central nervous system (CNS), hypothalamic-pituitary-adrenal (HPA) axis and autonomic nervous system (ANS) induced by prenatal stress (PS) is reflected in electrophysiological and epigenetic biomarkers. In this study, we aimed to find noninvasive epigenetic biomarkers of PS in the newborn salivary DNA. RESULTS: A total of 728 pregnant women were screened for stress exposure using Cohen Perceived Stress Scale (PSS), 164 women were enrolled, and 114 dyads were analyzed. Prenatal Distress Questionnaire (PDQ) was also administered to assess specific pregnancy worries. Transabdominal fetal electrocardiograms (taECG) were recorded to derive coupling between maternal and fetal heart rates resulting in a 'Fetal Stress Index' (FSI). Upon delivery, we collected maternal hair strands for cortisol measurements and newborn's saliva for epigenetic analyses. DNA was extracted from saliva samples, and DNA methylation was measured using EPIC BeadChip array (850 k CpG sites). Linear regression was used to identify associations between PSS/PDQ/FSI/Cortisol and DNA methylation. We found epigenome-wide significant associations for 5 CpG with PDQ and cortisol at FDR < 5%. Three CpGs were annotated to genes (Illumina Gene annotation file): YAP1, TOMM20 and CSMD1, and two CpGs were located approximately lay at 50 kb from SSBP4 and SCAMP1. In addition, two differentiated methylation regions (DMR) related to maternal stress measures PDQ and cortisol were found: DAXX and ARL4D. CONCLUSIONS: Genes annotated to these CpGs were found to be involved in secretion and transportation, nuclear signaling, Hippo signaling pathways, apoptosis, intracellular trafficking and neuronal signaling. Moreover, some CpGs are annotated to genes related to autism, post-traumatic stress disorder (PTSD) and schizophrenia. However, our results should be viewed as hypothesis generating until replicated in a larger sample. Early assessment of such noninvasive PS biomarkers will allow timelier detection of babies at risk and a more effective allocation of resources for early intervention programs to improve child development. A biomarker-guided early intervention strategy is the first step in the prevention of future health problems, reducing their personal and societal impact.

Long walk home: Magellanic penguins have strategies that lead them to areas where they can navigate most efficiently.

Understanding how animals move in dense environments where vision is compromised is a major challenge. We used GPS and dead-reckoning to examine the movement of Magellanic penguins commuting through vegetation that precluded long-distance vision. Birds leaving the nest followed the shortest, quickest route to the sea (the 'ideal path', or 'I-path') but return tracks depended where the birds left the water. Penguins arriving at the beach departure spot mirrored the departure. Most of those landing at a distance from the departure spot travelled slowly, obliquely to the coast at a more acute angle than a beeline trajectory to the nest. On crossing their I-path, these birds then followed this route quickly to their nests. This movement strategy saves birds distance, time and energy compared to a route along the beach and the into the colony on the I-track and saves time and energy compared to a beeline trajectory which necessitates slow travel in unfamiliar areas. This suggests that some animals adopt tactics that take them to an area where their navigational capacities are enhanced for efficient travel in challenging environments.

DNA methylation signature of chronic low-grade inflammation and its role in cardio-respiratory diseases.

We performed a multi-ethnic Epigenome Wide Association study on 22,774 individuals to describe the DNA methylation signature of chronic low-grade inflammation as measured by C-Reactive protein (CRP). We find 1,511 independent differentially methylated loci associated with CRP. These CpG sites show correlation structures across chromosomes, and are primarily situated in euchromatin, depleted in CpG islands. These genomic loci are predominantly situated in transcription factor binding sites and genomic enhancer regions. Mendelian randomization analysis suggests altered CpG methylation is a consequence of increased blood CRP levels. Mediation analysis reveals obesity and smoking as important underlying driving factors for changed CpG methylation. Finally, we find that an activated CpG signature significantly increases the risk for cardiometabolic diseases and COPD.