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Background: Studies describing the movement of free-ranging animals often use remotely collected global positioning system (GPS) data. However, such data typically only include intermittent positional information, with a sampling frequency that is constrained by battery life, producing sub-sampling effects that have the potential to bias interpretation. GPS-enhanced 'dead-reckoning' of animal movements is an alternative approach that utilises combined information from GPS devices, tri-axial accelerometers, and tri-axial magnetometers. Continuous detailed information of animal movement, activity and habitat selection can then be inferred from finer-scale GPS-enhanced dead-reckoning. It is also a useful technique to reveal the minutiae of an animal's movements such as path tortuosity. However, examples of studies using these approaches on terrestrial species are limited. Methods: Collars equipped with GPS, tri-axial accelerometer, and tri-axial magnetometer loggers were deployed on European badgers, Meles meles, to collect data on geo-position, acceleration and magnetic compass heading, respectively. This enabled us to compare GPS data with calculated GPS-enhanced dead-reckoned data. We also examined space use, distances travelled, speed of travel, and path tortuosity in relation to habitat type. Results: Nightly distances travelled were 2.2 times greater when calculated using GPS-enhanced dead-reckoned data than when calculated using GPS data alone. The use of dead-reckoned data reduced Kernel Density Estimates (KDE) of animal ranges to approximately half the size (0.21 km2) estimated using GPS data (0.46 km2). In contrast, Minimum Convex Polygon (MCP) methods showed that use of dead reckoned data yielded larger estimates of animal ranges than use of GPS-only data (0.35 and 0.27 km2, respectively). Analyses indicated that longer periods of activity were associated with greater travel distances and increased activity-related energy expenditure. Badgers also moved greater distances when they travelled at faster speeds and when the routes that they took were less tortuous. Nightly activity-related energy expenditure was not related to average travel speed or average ambient temperature but was positively related to the length of time individuals spent outside the sett (burrow). Badger activity varied with habitat type, with greater distance, speed, track tortuosity, and activity undertaken within woodland areas. Analyses of the effects of varying GPS sampling rate indicate that assessments of distance travelled depend on the sampling interval and the tortuosity of the animal's track. Where animal paths change direction rapidly, it becomes more important to use dead-reckoned data rather than GPS data alone to determine space use and distances. Conclusions: This study demonstrates the efficacy of GPS-enhanced dead-reckoning to collect high-resolution data on animal movements, activity, and locations and thereby identify subtle differences amongst individuals. This work also shows how the temporal resolution of position fixes plays a key role in the estimation of various movement metrics, such as travel speed and track tortuosity. [ABSTRACT FROM AUTHOR]

Background: Recent technological advances have resulted in low-cost GPS loggers that are small enough to be used on a range of seabirds, producing accurate location estimates (± 5 m) at sampling intervals as low as 1 s. However, tradeoffs between battery life and sampling frequency result in studies using GPS loggers on flying seabirds yielding locational data at a wide range of sampling intervals. Metrics derived from these data are known to be scale-sensitive, but quantification of these errors is rarely available. Very frequent sampling, coupled with limited movement, can result in measurement error, overestimating movement, but a much more pervasive problem results from sampling at long intervals, which grossly underestimates path lengths. Methods: We use fine-scale (1 Hz) GPS data from a range of albatrosses and petrels to study the effect of sampling interval on metrics derived from the data. The GPS paths were sub-sampled at increasing intervals to show the effect on path length (i.e. ground speed), turning angles, total distance travelled, as well as inferred behavioural states. Results: We show that distances (and per implication ground speeds) are overestimated (4% on average, but up to 20%) at the shortest sampling intervals (1–5 s) and underestimated at longer intervals. The latter bias is greater for more sinuous flights (underestimated by on average 40% when sampling > 1-min intervals) as opposed to straight flight (11%). Although sample sizes were modest, the effect of the bias seemingly varied with species, where species with more sinuous flight modes had larger bias. Sampling intervals also played a large role when inferring behavioural states from path length and turning angles. Conclusions: Location estimates from low-cost GPS loggers are appropriate to study the large-scale movements of seabirds when using coarse sampling intervals, but actual flight distances are underestimated. When inferring behavioural states from path lengths and turning angles, moderate sampling intervals (10–30 min) may provide more stable models, but the accuracy of the inferred behavioural states will depend on the time period associated with specific behaviours. Sampling rates have to be considered when comparing behaviours derived using varying sampling intervals and the use of bias-informed analyses are encouraged. [ABSTRACT FROM AUTHOR]

Although climate change is predicted to have a substantial effect on the energetic requirements of organisms, the longer-term implications are often unclear. Sloths are limited by the rate at which they can acquire energy and are unable to regulate core body temperature (Tb) to the extent seen in most mammals. Therefore, the metabolic impacts of climate change on sloths are expected to be profound. Here we use indirect calorimetry to measure the oxygen consumption (VO2) and Tb of highland and lowland two-fingered sloths (Choloepus hoffmanni) when exposed to a range of different ambient temperatures (Ta) (18 °C –34 °C), and additionally record changes in Tb and posture over several days in response to natural fluctuations in Ta. We use the resultant data to predict the impact of future climate change on the metabolic rate and Tb of the different sloth populations. The metabolic responses of sloths originating from the two sites differed at high Ta's, with lowland sloths invoking metabolic depression as temperatures rose above their apparent 'thermally-active zone' (TAZ), whereas highland sloths showed increased RMR. Based on climate change estimates for the year 2100, we predict that high-altitude sloths are likely to experience a substantial increase in metabolic rate which, due to their intrinsic energy processing limitations and restricted geographical plasticity, may make their survival untenable in a warming climate. [ABSTRACT FROM AUTHOR]

Biologging has proven to be a powerful approach to investigate diverse questions related to movement ecology across a range of spatiotemporal scales and increasingly relies on multidisciplinary expertise. However, the variety of animal‐borne equipment, coupled with little consensus regarding analytical approaches to interpret large, complex data sets presents challenges and makes comparison between studies and study species difficult. Here, we present a combined hardware and analytical approach for standardizing the collection, analysis, and interpretation of multisensor biologging data. Here, we present (i) a custom‐designed integrated multisensor collar (IMSC), which was field tested on 71 free‐ranging wild boar (Sus scrofa) over 2 years; (ii) a machine learning behavioral classifier capable of identifying six behaviors in free‐roaming boar, validated across individuals equipped with differing collar designs; and (iii) laboratory and field‐based calibration and accuracy assessments of animal magnetic heading measurements derived from raw magnetometer data. The IMSC capacity and durability exceeded expectations, with a 94% collar recovery rate and a 75% cumulative data recording success rate, with a maximum logging duration of 421 days. The behavioral classifier had an overall accuracy of 85% in identifying the six behavioral classes when tested on multiple collar designs and improved to 90% when tested on data exclusively from the IMSC. Both laboratory and field tests of magnetic compass headings were in precise agreement with expectations, with overall median magnetic headings deviating from ground truth observations by 1.7° and 0°, respectively. Although multisensor equipment and sophisticated analyses are now commonplace in biologging studies, the IMSC hardware and analytical framework presented here provide a valuable tool for biologging researchers and will facilitate standardization of biologging data across studies. In addition, we highlight the potential of additional analyses available using this framework that can be adapted for use in future studies on terrestrial mammals. [ABSTRACT FROM AUTHOR]

Background We characterized the global epidemiology and seasonality of human coronaviruses (HCoVs) OC43, NL63, 229E, and HKU1. Methods In this systematic review, we searched MEDLINE, EMBASE, Web of Science, SCOPUS, CINAHL, and backward citations for studies published until 1 September 2023. We included studies with ≥12 months of consecutive data and tested for ≥1 HCoV species. Case reports, review articles, animal studies, studies focusing on SARS-CoV-1, SARS-CoV-2, and/or Middle East respiratory syndrome, and those including <100 cases were excluded. Study quality and risk of bias were assessed using Joanna Briggs Institute Critical Appraisal Checklist tools. We reported the prevalence of all HCoVs and individual species. Seasonality was reported for studies that included ≥100 HCoVs annually. This study is registered with PROSPERO, CRD42022330902. Results A total of 201 studies (1 819 320 samples) from 68 countries were included. A high proportion were from China (19.4%; n = 39), whereas the Southern Hemisphere was underrepresented. Most were case series (77.1%, n = 155) with samples from secondary care (74.1%, n = 149). Seventeen (8.5%) studies included asymptomatic controls, whereas 76 (37.8%) reported results for all 4 HCoV species. Overall, OC43 was the most prevalent HCoV. Median test positivity of OC43 and NL63 was higher in children, and 229E and HKU1 in adults. Among 18 studies that described seasonality (17 from the Northern Hemisphere), circulation of all HCoVs mostly peaked during cold months. Conclusions In our comprehensive review, few studies reported the prevalence of individual HCoVs or seasonality. Further research on the burden and circulation of HCoVs is needed, particularly from Africa, South Asia, and Central/South America. [ABSTRACT FROM AUTHOR]

Educators teaching at community-engaged universities can benefit from learning best practices to prepare 21st century citizens. This case study explores why undergraduate students in an online volunteer management course select an organization to complete a community-engaged learning activity. Theory-based teaching strategies integrating the characteristics of quality community-engaged learning are outlined. Qualitative analysis of student reflections resulted in six categories representing student choices including: social connections, exploring interests, positive human connection, organizational engagement, aligning values, and commitment to the cause. The lessons learned can help educators enhance students' learning by nurturing diverse community connections, establishing student-centered course goals, and constructing significant learning strategies. [ABSTRACT FROM AUTHOR]

Despite extensive research on 5-methylcytosine (5mC) in relation to smoking, there has been limited exploration into the interaction between smoking and 5-hydroxymethylcytosine (5hmC). In this study, total DNA methylation (5mC+5hmC), true DNA methylation (5mC) and hydroxymethylation (5hmC) levels were profiled utilizing conventional bisulphite (BS) and oxidative bisulphite (oxBS) treatment, measured with the Illumina Infinium Methylation EPIC BeadChip. An epigenome-wide association study (EWAS) of 5mC+5hmC methylation revealed a total of 38,575 differentially methylated positions (DMPs) and 2023 differentially methylated regions (DMRs) associated with current smoking, along with 82 DMPs and 76 DMRs associated with former smoking (FDR-adjusted p < 0.05). Additionally, a focused examination of 5mC identified 33 DMPs linked to current smoking and 1 DMP associated with former smoking (FDR-adjusted p < 0.05). In the 5hmC category, eight DMPs related to current smoking and two DMPs tied to former smoking were identified, each meeting a suggestive threshold (p < 1 × 10−5). The substantial number of recognized DMPs, including 5mC+5hmC (7069/38,575, 2/82), 5mC (0/33, 1/1), and 5hmC (2/8, 0/2), have not been previously reported. Our findings corroborated previously established methylation positions and revealed novel candidates linked to tobacco smoking. Moreover, the identification of hydroxymethylated CpG sites with suggestive links provides avenues for future research. [ABSTRACT FROM AUTHOR]

Observing animals in the wild often poses extreme challenges, but animal‐borne accelerometers are increasingly revealing unobservable behaviours. Automated machine learning streamlines behaviour identification from the substantial datasets generated during multi‐animal, long‐term studies; however, the accuracy of such models depends on the qualities of the training data. We examined how data processing influenced the predictive accuracy of random forest (RF) models, leveraging the easily observed domestic cat (Felis catus) as a model organism for terrestrial mammalian behaviours. Nine indoor domestic cats were equipped with collar‐mounted tri‐axial accelerometers, and behaviours were recorded alongside video footage. From this calibrated data, eight datasets were derived with (i) additional descriptive variables, (ii) altered frequencies of acceleration data (40 Hz vs. a mean over 1 s) and (iii) standardised durations of different behaviours. These training datasets were used to generate RF models that were validated against calibrated cat behaviours before identifying the behaviours of five free‐ranging tag‐equipped cats. These predictions were compared to those identified manually to validate the accuracy of the RF models for free‐ranging animal behaviours. RF models accurately predicted the behaviours of indoor domestic cats (F‐measure up to 0.96) with discernible improvements observed with post‐data‐collection processing. Additional variables, standardised durations of behaviours and higher recording frequencies improved model accuracy. However, prediction accuracy varied with different behaviours, where high‐frequency models excelled in identifying fast‐paced behaviours (e.g. locomotion), whereas lower‐frequency models (1 Hz) more accurately identified slower, aperiodic behaviours such as grooming and feeding, particularly when examining free‐ranging cat behaviours. While RF modelling offered a robust means of behaviour identification from accelerometer data, field validations were important to validate model accuracy for free‐ranging individuals. Future studies may benefit from employing similar data processing methods that enhance RF behaviour identification accuracy, with extensive advantages for investigations into ecology, welfare and management of wild animals. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. Wearable sensors inform on aquaculture and marine-conservation strategies. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 selfreported 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Epigenomic (e.g., DNA methylation [DNAm]) changes have been hypothesized as intermediate step linking environmental exposures with allergic disease. Associations between individual DNAm at CpGs and allergic diseases have been reported, but their joint predictive capability is unknown. Methods: Data were obtained from 240 children of the German LISA cohort. DNAm was measured in blood clots at 6 (N = 234) and 10 years (N = 227) using the Illumina EPIC chip. Presence of aeroallergen sensitization was measured in blood at 6, 10, and 15 years. We calculated six methylation risk scores (MRS) for allergy‐related phenotypes, like total and specific IgE, asthma, or any allergies, based on available publications and assessed their performances both cross‐sectionally (biomarker) and prospectively (predictor of the disease). Dose–response associations between aeroallergen sensitization and MRS were evaluated. Results: All six allergy‐related MRS were highly correlated (r >.86), and seven CpGs were included in more than one MRS. Cross‐sectionally, we observed an 81% increased risk for aeroallergen sensitization at 6 years with an increased MRS by one standard deviation (best‐performing MRS, 95% confidence interval = [43%; 227%]). Significant associations were also seen cross‐sectionally at 10 years and prospectively, though the effect of the latter was attenuated when restricted to participants not sensitized at baseline. A clear dose–response relationship with levels of aeroallergen sensitization could be established cross‐sectionally, but not prospectively. Conclusion: We found good classification and prediction capabilities of calculated allergy‐related MRS cross‐sectionally, underlining the relevance of altered gene‐regulation in allergic diseases and providing insights into potential DNAm biomarkers of aeroallergen sensitization. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. Chronic inflammation, marked by C-reactive protein, has been associated with changes in methylation, but the causal relationship is unclear. Here, the authors perform a Epigenome-wide association meta-analysis for C-reactive protein levels and find that these methylation changes are likely the consequence of inflammation and could contribute to disease. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Locomotion is often a necessity for animal survival and can account for a large proportion of an individual's energy budget. Therefore, determining the energy costs of locomotion is an important part of understanding the interaction between an animal and its environment. Measures of animal acceleration, specifically 'dynamic body acceleration' (DBA) has proved to be a useful proxy of the energy cost of locomotion. However, few studies have considered the effects of interacting factors such as the animal's speed or changes to the terrain slope on the putative acceleration versus energy expenditure relationship and how this may affect the relationship between DBA and energy expenditure. Methods: Here we conducted a methodological study to evaluate the ability of the metric 'vectorial dynamic body acceleration', VeDBA, obtained from tri-axial accelerometer data loggers, to act as a proxy for energy expenditure in non-uniform environments. We used indirect calorimetry to measure the oxygen consumption (V̇O2) of domestic sheep (Ovis aries) that were exposed to different ambient temperatures when immobile (resting) and that walked at various speeds (0.8 to 2.9 km h−1) and slope angles (− 6° to 6°) on a treadmill while simultaneously measuring tri-axial acceleration recorded at 40 Hz by body-mounted tags. Results: The lower critical temperature of sheep was identified as 18 °C, and V̇O2 when they were immobile was 3.67 mL O2 kg−1 min−1. There were positive relationships between V̇O2, VeDBA, and speed of walking. However, VeDBA correlated less well with V̇O2 when the terrain slope either inclined or declined. Conclusions: We advocate caution when using DBA metrics for establishing energy use in animals moving over uneven terrain and suggest that each study species or location must be examined on a case-by-case basis. Reliance upon the relationship described between acceleration and energy expenditure on horizontal-surface treadmills can lead to potential under- or over-estimates of energy expenditure when animals walk on uneven or inclined ground. [ABSTRACT FROM AUTHOR]

Global warming is expected to affect movement‐related thermoregulation in ectotherms, but the likely effects on thermoconforming lizards, which spend little energy in thermoregulation behavior, are unclear. We used the Guatemalan beaded lizard (Heloderma charlesbogerti) as a model thermoconforming species to investigate the effects of ambient temperature and barometric pressure (a cue for rain in the study area) on activity intensity and the structure of movement paths. We tracked 12 individuals over a total of 148 animal days during the wet season of 2019 using Global Positioning System tags and triaxial accelerometry. We found a clear positive effect of ambient temperature on activity (using vectorial dynamic body acceleration [VeDBA]) and step length of lizard movements. The movement also became more directional (longer step lengths and smaller turning angles) with increasing ambient temperatures. There was a small negative effect of barometric pressure on VeDBA. We propose that our patterns are indicative of internal state changes in the animals, as they move from a state of hunger, eliciting foraging, which is enhanced by lower temperatures and rainfall to a thermally stressed state, which initiates shelter‐seeking. Our findings highlight the sensitivity of this species to temperature change, show that not all thermoconforming lizards are thermal generalists, and indicate that predicted regional increases in temperature and reduction in rainfall are likely to negatively impact this species by reducing the width of their operational thermal window. [ABSTRACT FROM AUTHOR]

Dystonia is a prevalent, heterogeneous movement disorder characterized by involuntarily abnormal postures. Biomarkers of dystonia are notoriously lacking. Here, a biomarker is reported for histone lysine methyltransferase (KMT2B)-deficient dystonia, a leading subtype among the individually rare monogenic dystonias. It was derived by applying a support vector machine to an episignature of 113 DNA CpG sites, which, in blood cells, showed significant epigenome-wide association with KMT2B deficiency and at least 1× log-fold change of methylation. This classifier was accurate both when tested on the general population and on samples with various other deficiencies of the epigenetic machinery, thus allowing for definitive evaluation of variants of uncertain significance and identifying patients who may profit from deep brain stimulation, a highly successful treatment in KMT2B-deficient dystonia. Methylation was increased in KMT2B deficiency at all 113 CpG sites. The coefficients of variation of the normalized methylation levels at these sites also perfectly classified the samples with KMT2B-deficient dystonia. Moreover, the mean of the normalized methylation levels correlated well with the age at onset of dystonia (P = 0.003)-being lower in samples with late or incomplete penetrance-thus serving as a predictor of disease onset and severity. Similarly, it may also function in monitoring the recently envisioned treatment of KMT2B deficiency by inhibition of DNA methylation. [ABSTRACT FROM AUTHOR]

Leg rings are frequently used to mark aquatic birds in order to identify individuals, and study population dynamics and migration patterns, with the proviso being that the rings should not affect the birds. The effects of tags and rings are of particular interest in diving birds because any change in body shape could impact swimming efficiency and costs, as water is almost a thousand times denser than air. We attached tri‐axial accelerometers to both ringed and unringed breeding Imperial Shags Leucocarbo atriceps to assess dive performance based on descent angle, descent rate, power stroke rate, power stroke peak acceleration amplitude and Vectorial Dynamic Body Acceleration (VeDBA) as a proxy for energy expenditure. Ringed birds, especially females, had a higher foot‐stroke amplitude than unringed animals. In addition, the overall efficiency of the ringed individuals, as expressed by the descent rate per unit VeDBA, was compromised (by 3.5% in females and 4.3% in males) compared with unringed birds. We conclude that leg rings change the diving performance of Imperial Shags, although the effect is small and may not affect reproductive success. However, given that birds are typically ringed for life, we urge researchers to be particularly careful about the potential cumulative effect of attaching leg rings to foot‐propelled diving species. [ABSTRACT FROM AUTHOR]

The energy used by animals is influenced by intrinsic (e.g. physiological) and extrinsic (e.g. environmental) factors. Accelerometers within biologging devices have proven useful for assessing energy expenditures and their behavioural context in free-ranging animals. However, certain assumptions are frequently made when acceleration is used as a proxy for energy expenditure, with factors, such as environmental variation (e.g. ambient temperature or slope of terrain), seldom accounted for. To determine the possible interactions between behaviour, energy expenditure and the environment (ambient temperature and terrain slope), the rate of oxygen consumption ( V ˙ O 2 ) was measured in pygmy goats (Capra hircus aegarus) using open-flow indirect calorimetry. The effect of temperature (9.7–31.5 °C) on resting energy expenditure was measured. The relationship between V ˙ O 2 and dynamic body acceleration (DBA) was measured at different walking speeds (0.8–3.0 km h−1) and on different inclines (0, + 15°, − 15°). The daily behaviour of individuals was measured in two enclosures: enclosure A (level terrain during summer) and enclosure B (sloped terrain during winter) and per diem energy expenditures of behaviours estimated using behaviour, DBA, temperature, terrain slope and V ˙ O 2 . During rest, energy expenditure increased below 22 °C and above 30.5 °C. V ˙ O 2 (ml min−1) increased with DBA when walking on the level. Walking uphill (+ 15°) increased energetic costs three-fold, whereas walking downhill (− 15°) increased energetic costs by one third. Based on these results, although activity levels were higher in animals in enclosure A during summer, energy expenditure was found to be significantly higher in the sloped enclosure B in winter (means of enclosures A and B: 485.3 ± 103.6 kJ day−1 and 744.5 ± 132.4 kJ day−1). We show that it is essential to account for extrinsic factors when calculating animal energy budgets. Our estimates of the impacts of extrinsic factors should be applicable to other free ranging ungulates. [ABSTRACT FROM AUTHOR]

Common carotid intima-media thickness (cIMT) is an index of subclinical atherosclerosis that is associated with ischemic stroke and coronary artery disease (CAD). We undertook a cross-sectional epigenome-wide association study (EWAS) of measures of cIMT in 6400 individuals. Mendelian randomization analysis was applied to investigate the potential causal role of DNA methylation in the link between atherosclerotic cardiovascular risk factors and cIMT or clinical cardiovascular disease. The CpG site cg05575921 was associated with cIMT (beta = −0.0264, p value = 3.5 × 10–8) in the discovery panel and was replicated in replication panel (beta = −0.07, p value = 0.005). This CpG is located at chr5:81649347 in the intron 3 of the aryl hydrocarbon receptor repressor gene (AHRR). Our results indicate that DNA methylation at cg05575921 might be in the pathway between smoking, cIMT and stroke. Moreover, in a region-based analysis, 34 differentially methylated regions (DMRs) were identified of which a DMR upstream of ALOX12 showed the strongest association with cIMT (p value = 1.4 × 10–13). In conclusion, our study suggests that DNA methylation may play a role in the link between cardiovascular risk factors, cIMT and clinical cardiovascular disease. [ABSTRACT FROM AUTHOR]

Background: The difference between an individual's chronological and DNA methylation predicted age (DNAmAge), termed DNAmAge acceleration (DNAmAA), can capture life-long environmental exposures and age-related physiological changes reflected in methylation status. Several studies have linked DNAmAA to morbidity and mortality, yet its relationship with kidney function has not been assessed. We evaluated the associations between seven DNAm aging and lifespan predictors (as well as GrimAge components) and five kidney traits (estimated glomerular filtration rate [eGFR], urine albumin-to-creatinine ratio [uACR], serum urate, microalbuminuria and chronic kidney disease [CKD]) in up to 9688 European, African American and Hispanic/Latino individuals from seven population-based studies. Results: We identified 23 significant associations in our large trans-ethnic meta-analysis (p < 1.43E−03 and consistent direction of effect across studies). Age acceleration measured by the Extrinsic and PhenoAge estimators, as well as Zhang's 10-CpG epigenetic mortality risk score (MRS), were associated with all parameters of poor kidney health (lower eGFR, prevalent CKD, higher uACR, microalbuminuria and higher serum urate). Six of these associations were independently observed in European and African American populations. MRS in particular was consistently associated with eGFR (β = − 0.12, 95% CI = [− 0.16, − 0.08] change in log-transformed eGFR per unit increase in MRS, p = 4.39E−08), prevalent CKD (odds ratio (OR) = 1.78 [1.47, 2.16], p = 2.71E-09) and higher serum urate levels (β = 0.12 [0.07, 0.16], p = 2.08E−06). The "first-generation" clocks (Hannum, Horvath) and GrimAge showed different patterns of association with the kidney traits. Three of the DNAm-estimated components of GrimAge, namely adrenomedullin, plasminogen-activation inhibition 1 and pack years, were positively associated with higher uACR, serum urate and microalbuminuria. Conclusion: DNAmAge acceleration and DNAm mortality predictors estimated in whole blood were associated with multiple kidney traits, including eGFR and CKD, in this multi-ethnic study. Epigenetic biomarkers which reflect the systemic effects of age-related mechanisms such as immunosenescence, inflammaging and oxidative stress may have important mechanistic or prognostic roles in kidney disease. Our study highlights new findings linking kidney disease to biological aging, and opportunities warranting future investigation into DNA methylation biomarkers for prognostic or risk stratification in kidney disease. [ABSTRACT FROM AUTHOR]

Background: Information on long-term alcohol consumption is relevant for medical and public health research, disease therapy, and other areas. Recently, DNA methylation-based inference of alcohol consumption from blood was reported with high accuracy, but these results were based on employing the same dataset for model training and testing, which can lead to accuracy overestimation. Moreover, only subsets of alcohol consumption categories were used, which makes it impossible to extrapolate such models to the general population. By using data from eight population-based European cohorts (N = 4677), we internally and externally validated the previously reported biomarkers and models for epigenetic inference of alcohol consumption from blood and developed new models comprising all data from all categories. Results: By employing data from six European cohorts (N = 2883), we empirically tested the reproducibility of the previously suggested biomarkers and prediction models via ten-fold internal cross-validation. In contrast to previous findings, all seven models based on 144-CpGs yielded lower mean AUCs compared to the models with less CpGs. For instance, the 144-CpG heavy versus non-drinkers model gave an AUC of 0.78 ± 0.06, while the 5 and 23 CpG models achieved 0.83 ± 0.05, respectively. The transportability of the models was empirically tested via external validation in three independent European cohorts (N = 1794), revealing high AUC variance between datasets within models. For instance, the 144-CpG heavy versus non-drinkers model yielded AUCs ranging from 0.60 to 0.84 between datasets. The newly developed models that considered data from all categories showed low AUCs but gave low AUC variation in the external validation. For instance, the 144-CpG heavy and at-risk versus light and non-drinkers model achieved AUCs of 0.67 ± 0.02 in the internal cross-validation and 0.61–0.66 in the external validation datasets. Conclusions: The outcomes of our internal and external validation demonstrate that the previously reported prediction models suffer from both overfitting and accuracy overestimation. Our results show that the previously proposed biomarkers are not yet sufficient for accurate and robust inference of alcohol consumption from blood. Overall, our findings imply that DNA methylation prediction biomarkers and models need to be improved considerably before epigenetic inference of alcohol consumption from blood can be considered for practical applications. [ABSTRACT FROM AUTHOR]

Animal-attached devices have transformed our understanding of vertebrate ecology. To minimize any associated harm, researchers have long advocated that tag masses should not exceed 3% of carrier body mass. However, this ignores tag forces resulting from animal movement. Using data from collar-attached accelerometers on 10 diverse free-ranging terrestrial species from koalas to cheetahs, we detail a tag-based acceleration method to clarify acceptable tag mass limits. We quantify animal athleticism in terms of fractions of animal movement time devoted to different collar-recorded accelerations and convert those accelerations to forces (acceleration × tag mass) to allow derivation of any defined force limits for specified fractions of any animal's active time. Specifying that tags should exert forces that are less than 3% of the gravitational force exerted on the animal's body for 95% of the time led to corrected tag masses that should constitute between 1.6% and 2.98% of carrier mass, depending on athleticism. Strikingly, in four carnivore species encompassing two orders of magnitude in mass (ca 2–200 kg), forces exerted by '3%' tags were equivalent to 4–19% of carrier body mass during moving, with a maximum of 54% in a hunting cheetah. This fundamentally changes how acceptable tag mass limits should be determined by ethics bodies, irrespective of the force and time limits specified. [ABSTRACT FROM AUTHOR]

Background: Information on long-term alcohol consumption is relevant for medical and public health research, disease therapy, and other areas. Recently, DNA methylation-based inference of alcohol consumption from blood was reported with high accuracy, but these results were based on employing the same dataset for model training and testing, which can lead to accuracy overestimation. Moreover, only subsets of alcohol consumption categories were used, which makes it impossible to extrapolate such models to the general population. By using data from eight population-based European cohorts (N = 4677), we internally and externally validated the previously reported biomarkers and models for epigenetic inference of alcohol consumption from blood and developed new models comprising all data from all categories. Results: By employing data from six European cohorts (N = 2883), we empirically tested the reproducibility of the previously suggested biomarkers and prediction models via ten-fold internal cross-validation. In contrast to previous findings, all seven models based on 144-CpGs yielded lower mean AUCs compared to the models with less CpGs. For instance, the 144-CpG heavy versus non-drinkers model gave an AUC of 0.78 ± 0.06, while the 5 and 23 CpG models achieved 0.83 ± 0.05, respectively. The transportability of the models was empirically tested via external validation in three independent European cohorts (N = 1794), revealing high AUC variance between datasets within models. For instance, the 144-CpG heavy versus non-drinkers model yielded AUCs ranging from 0.60 to 0.84 between datasets. The newly developed models that considered data from all categories showed low AUCs but gave low AUC variation in the external validation. For instance, the 144-CpG heavy and at-risk versus light and non-drinkers model achieved AUCs of 0.67 ± 0.02 in the internal cross-validation and 0.61–0.66 in the external validation datasets. Conclusions: The outcomes of our internal and external validation demonstrate that the previously reported prediction models suffer from both overfitting and accuracy overestimation. Our results show that the previously proposed biomarkers are not yet sufficient for accurate and robust inference of alcohol consumption from blood. Overall, our findings imply that DNA methylation prediction biomarkers and models need to be improved considerably before epigenetic inference of alcohol consumption from blood can be considered for practical applications. [ABSTRACT FROM AUTHOR]

Background: The prevalence of obesity and its related chronic diseases have been increasing especially in Asian countries. Obesity-related genetic variants have been identified, but these explain little of the variation in BMI. Recent studies reported associations between DNA methylation and obesity, mostly in non-Asian populations. Methods: We performed an epigenome-wide association study (EWAS) on general adiposity (body mass index, BMI) and abdominal adiposity (waist circumference, WC) in 409 multi-ethnic Asian individuals and replicated BMI and waist-associated DNA methylation CpGs identified in other populations. The cross-lagged panel model and Mendelian randomization were used to assess the temporal relationship between methylation and BMI. The temporal relationship between the identified CpGs and inflammation and metabolic markers was also examined. Results: EWAS identified 116 DNA methylation CpGs independently associated with BMI and eight independently associated with WC at false discovery rate PFDR < 0.05 in 409 Asian samples. We replicated 110 BMI-associated CpGs previously reported in Europeans and identified six novel BMI-associated CpGs and two novel WC-associated CpGs. We observed high consistency in association direction of effect compared to studies in other populations. Causal relationship analyses indicated that BMI was more likely to be the cause of DNA methylation alteration, rather than the consequence. The causal analyses using BMI-associated methylation risk score also suggested that higher levels of the inflammation marker IL-6 were likely the consequence of methylation change. Conclusion: Our study provides evidence of an association between obesity and DNA methylation in multi-ethnic Asians and suggests that obesity can drive methylation change. The results also suggested possible causal influence that obesity-related methylation changes might have on inflammation and lipoprotein levels. [ABSTRACT FROM AUTHOR]

The time that animals spend travelling at various speeds and the tortuosity of their movement paths are two of the many things that affect space‐use by animals. In this, high turn rates are predicted to be energetically costly, especially at high travel speeds, which implies that animals should modulate their speed according to path characteristics. When animals move so as to maximize distance and minimize metabolic energy expenditure, they travel most efficiently at the speed that gives them a minimum cost of transport (COTmin), a well‐defined point for animals that move entirely in fluid media. Theoretical considerations show though, that land animals should travel at their maximum speed to minimize COT, which they do not, instead travelling at walking pace. So, to what extent does COTmin depend on speed and turn rate and how might this relate to movement paths? We measured oxygen consumption in humans walking along paths with varied tortuosity at defined speeds to demonstrate that the energetic costs of negotiating these paths increase disproportionately with both speed and angular velocity. This resulted in the COTmin occurring at very low speeds, and these COTmin speeds reduced with increased path tortuosity and angular velocity. Logged movement data from six free‐ranging terrestrial species underpinned this because all individuals turned with greater angular velocity the slower their travel speeds across their full speed range. It seems, therefore, that land animals may strive to achieve minimum movement costs by reducing speed with increasing path variability, providing one of many possible explanations as to why speed is much lower than currently predicted based on lab measurements of mammalian locomotor performance. [ABSTRACT FROM AUTHOR]

Background: Quantifying metabolic rate in free-living animals is invaluable in understanding the costs of behaviour and movement for individuals and communities. Dynamic body acceleration (DBA) metrics, such as vectoral DBA (VeDBA), are commonly used as proxies for the energy expenditure of movement but are of limited applicability for slow-moving species. It has recently been suggested that metrics based on angular velocity might be better suited to characterise their energetics. We investigated whether a novel metric—the 'Rate of change of Rotational Movement (RocRM)', calculated from the vectoral sum of change in the pitch, roll and yaw/heading axes over a given length of time, is a suitable proxy for energy expenditure. Results: We found that RocRM can be used as an alternative energy expenditure proxy in a slow-moving benthic invertebrate. Eleven Giant spider conchs Lambis truncata (collected in the Red Sea) were instrumented with multiple channel (Daily Diary) tags and kept in sealed chambers for 5 h while their oxygen consumption, V̇O2, was measured. We found RocRM to be positively correlated with V̇O2, this relationship being affected by the time-step (i.e. the range of the calculated differential) of the RocRM. Time steps of 1, 5, 10 and 60 s yielded an explained variability of between 15 and 31%. The relationship between V̇O2 and VeDBA was not statistically significant, suggesting RocRM to provide more accurate estimations of metabolic rates in L. truncata. Conclusions: RocRM proved to be a statistically significant predictor of V̇O2 where VeDBA did not, validating the approach of using angular-based metrics over dynamic movement-based ones for slower moving animals. Further work is required to validate the use of RocRM for other species, particularly in animals with minimally dynamic movement, to better understand energetic costs of whole ecosystems. Unexplained variability in the models might be a consequence of the methodology used, but also likely a result of conch activity that does not manifest in movement of the shell. Additionally, density plots of mean RocRM at each time-step suggest differences in movement scales, which may collectively be useful as a species fingerprint of movement going forward. [ABSTRACT FROM AUTHOR]

Here we examine the association between DNA methylation in circulating leukocytes and blood lipids in a multi-ethnic sample of 16,265 subjects. We identify 148, 35, and 4 novel associations among Europeans, African Americans, and Hispanics, respectively, and an additional 186 novel associations through a trans-ethnic meta-analysis. We observe a high concordance in the direction of effects across racial/ethnic groups, a high correlation of effect sizes between high-density lipoprotein and triglycerides, a modest overlap of associations with epigenome-wide association studies of other cardio-metabolic traits, and a largely non-overlap with lipid loci identified to date through genome-wide association studies. Thirty CpGs reached significance in at least 2 racial/ethnic groups including 7 that showed association with the expression of an annotated gene. CpGs annotated to CPT1A showed evidence of being influenced by triglycerides levels. DNA methylation levels of circulating leukocytes show robust and consistent association with blood lipid levels across multiple racial/ethnic groups. Abnormal blood lipid levels are important risk factors for cardiovascular and other various diseases. Here the authors conduct a large-scale multi-ethnic epigenome-wide association study combined with epigenetic (cis-QTL and eQTM) data, and identify CpG-lipid traits associations that are specific to or common across racial/ethnic groups. [ABSTRACT FROM AUTHOR]

Background: Animal-attached devices can be used on cryptic species to measure their movement and behaviour, enabling unprecedented insights into fundamental aspects of animal ecology and behaviour. However, direct observations of subjects are often still necessary to translate biologging data accurately into meaningful behaviours. As many elusive species cannot easily be observed in the wild, captive or domestic surrogates are typically used to calibrate data from devices. However, the utility of this approach remains equivocal. Methods: Here, we assess the validity of using captive conspecifics, and phylogenetically-similar domesticated counterparts (surrogate species) for calibrating behaviour classification. Tri-axial accelerometers and tri-axial magnetometers were used with behavioural observations to build random forest models to predict the behaviours. We applied these methods using captive Alpine ibex (Capra ibex) and a domestic counterpart, pygmy goats (Capra aegagrus hircus), to predict the behaviour including terrain slope for locomotion behaviours of captive Alpine ibex. Results: Behavioural classification of captive Alpine ibex and domestic pygmy goats was highly accurate (> 98%). Model performance was reduced when using data split per individual, i.e., classifying behaviour of individuals not used to train models (mean ± sd = 56.1 ± 11%). Behavioural classifications using domestic counterparts, i.e., pygmy goat observations to predict ibex behaviour, however, were not sufficient to predict all behaviours of a phylogenetically similar species accurately (> 55%). Conclusions: We demonstrate methods to refine the use of random forest models to classify behaviours of both captive and free-living animal species. We suggest there are two main reasons for reduced accuracy when using a domestic counterpart to predict the behaviour of a wild species in captivity; domestication leading to morphological differences and the terrain of the environment in which the animals were observed. We also identify limitations when behaviour is predicted in individuals that are not used to train models. Our results demonstrate that biologging device calibration needs to be conducted using: (i) with similar conspecifics, and (ii) in an area where they can perform behaviours on terrain that reflects that of species in the wild. [ABSTRACT FROM AUTHOR]

Background: The difference between an individual's chronological and DNA methylation predicted age (DNAmAge), termed DNAmAge acceleration (DNAmAA), can capture life-long environmental exposures and age-related physiological changes reflected in methylation status. Several studies have linked DNAmAA to morbidity and mortality, yet its relationship with kidney function has not been assessed. We evaluated the associations between seven DNAm aging and lifespan predictors (as well as GrimAge components) and five kidney traits (estimated glomerular filtration rate [eGFR], urine albumin-to-creatinine ratio [uACR], serum urate, microalbuminuria and chronic kidney disease [CKD]) in up to 9688 European, African American and Hispanic/Latino individuals from seven population-based studies. Results: We identified 23 significant associations in our large trans-ethnic meta-analysis (p < 1.43E−03 and consistent direction of effect across studies). Age acceleration measured by the Extrinsic and PhenoAge estimators, as well as Zhang's 10-CpG epigenetic mortality risk score (MRS), were associated with all parameters of poor kidney health (lower eGFR, prevalent CKD, higher uACR, microalbuminuria and higher serum urate). Six of these associations were independently observed in European and African American populations. MRS in particular was consistently associated with eGFR (β = − 0.12, 95% CI = [− 0.16, − 0.08] change in log-transformed eGFR per unit increase in MRS, p = 4.39E−08), prevalent CKD (odds ratio (OR) = 1.78 [1.47, 2.16], p = 2.71E-09) and higher serum urate levels (β = 0.12 [0.07, 0.16], p = 2.08E−06). The "first-generation" clocks (Hannum, Horvath) and GrimAge showed different patterns of association with the kidney traits. Three of the DNAm-estimated components of GrimAge, namely adrenomedullin, plasminogen-activation inhibition 1 and pack years, were positively associated with higher uACR, serum urate and microalbuminuria. Conclusion: DNAmAge acceleration and DNAm mortality predictors estimated in whole blood were associated with multiple kidney traits, including eGFR and CKD, in this multi-ethnic study. Epigenetic biomarkers which reflect the systemic effects of age-related mechanisms such as immunosenescence, inflammaging and oxidative stress may have important mechanistic or prognostic roles in kidney disease. Our study highlights new findings linking kidney disease to biological aging, and opportunities warranting future investigation into DNA methylation biomarkers for prognostic or risk stratification in kidney disease. [ABSTRACT FROM AUTHOR]

Background: The metabolic syndrome (MetS), defined by the simultaneous clustering of cardio-metabolic risk factors, is a significant worldwide public health burden with an estimated 25% prevalence worldwide. The pathogenesis of MetS is not entirely clear and the use of molecular level data could help uncover common pathogenic pathways behind the observed clustering. Methods: Using a highly multiplexed aptamer-based affinity proteomics platform, we examined associations between plasma proteins and prevalent and incident MetS in the KORA cohort (n = 998) and replicated our results for prevalent MetS in the HUNT3 study (n = 923). We applied logistic regression models adjusted for age, sex, smoking status, and physical activity. We used the bootstrap ranking algorithm of least absolute shrinkage and selection operator (LASSO) to select a predictive model from the incident MetS associated proteins and used area under the curve (AUC) to assess its performance. Finally, we investigated the causal effect of the replicated proteins on MetS using two-sample Mendelian randomization. Results: Prevalent MetS was associated with 116 proteins, of which 53 replicated in HUNT. These included previously reported proteins like leptin, and new proteins like NTR domain-containing protein 2 and endoplasmic reticulum protein 29. Incident MetS was associated with 14 proteins in KORA, of which 13 overlap the prevalent MetS associated proteins with soluble advanced glycosylation end product-specific receptor (sRAGE) being unique to incident MetS. The LASSO selected an eight-protein predictive model with an (AUC = 0.75; 95% CI = 0.71–0.79) in KORA. Mendelian randomization suggested causal effects of three proteins on MetS, namely apolipoprotein E2 (APOE2) (Wald-Ratio = − 0.12, Wald-p = 3.63e−13), apolipoprotein B (APOB) (Wald-Ratio = − 0.09, Wald-p = 2.54e−04) and proto-oncogene tyrosine-protein kinase receptor (RET) (Wald-Ratio = 0.10, Wald-p = 5.40e−04). Conclusions: Our findings offer new insights into the plasma proteome underlying MetS and identify new protein associations. We reveal possible casual effects of APOE2, APOB and RET on MetS. Our results highlight protein candidates that could potentially serve as targets for prevention and therapy. [ABSTRACT FROM AUTHOR]

Animals alter their habitat use in response to the energetic demands of movement ('energy landscapes') and the risk of predation ('the landscape of fear'). Recent research suggests that animals also select habitats and move in ways that minimise their chance of temporarily losing control of movement and thereby suffering slips, falls, collisions or other accidents, particularly when the consequences are likely to be severe (resulting in injury or death). We propose that animals respond to the costs of an 'accident landscape' in conjunction with predation risk and energetic costs when deciding when, where, and how to move in their daily lives. We develop a novel theoretical framework describing how features of physical landscapes interact with animal size, morphology, and behaviour to affect the risk and severity of accidents, and predict how accident risk might interact with predation risk and energetic costs to dictate movement decisions across the physical landscape. Future research should focus on testing the hypotheses presented here for different real‐world systems to gain insight into the relative importance of theorised effects in the field. [ABSTRACT FROM AUTHOR]

Step selection analysis (SSA) is a fundamental technique for uncovering the drivers of animal movement decisions. Its typical use has been to view an animal as 'selecting' each measured location, given its current (and possibly previous) locations. Although an animal is unlikely to make decisions precisely at the times its locations are measured, if data are gathered at a relatively low frequency (every few minutes or hours) this is often the best that can be done. Nowadays, though, tracking data are increasingly gathered at very high frequencies, often ≥1 Hz, so it may be possible to exploit these data to perform more behaviourally‐meaningful step selection analysis.Here, we present a technique to do this. We first use an existing algorithm to determine the turning‐points in an animal's movement path. We define a 'step' to be a straight‐line movement between successive turning‐points. We then construct a generalised version of integrated SSA (iSSA), called time‐varying iSSA (tiSSA), which deals with the fact that turning‐points are usually irregularly spaced in time. We demonstrate the efficacy of tiSSA by application to data on both simulated animals and free‐ranging goats Capra aegagrus hircus, comparing our results to those of regular iSSA with locations that are separated by a constant time‐interval.Using (regular) iSSA with constant time‐steps can give results that are misleading compared to using tiSSA with the actual turns made by the animals. Furthermore, tiSSA can be used to infer covariates that are dependent on the time between turns, which is not possible with regular iSSA. As an example, we show that our study animals tend to spend less time between successive turns when the ground is rockier and/or the temperature is hotter.By constructing a step selection technique that works between observed turning‐points of animals, we enable step selection to be used on high‐frequency movement data, which are becoming increasingly prevalent in modern biologging studies. Furthermore, since turning‐points can be viewed as decisions, our method places step selection analysis on a more behaviourally‐meaningful footing compared to previous techniques. [ABSTRACT FROM AUTHOR]

Background: DNA methylation is a key epigenetic modification that can directly affect gene regulation. DNA methylation is highly influenced by environmental factors such as cigarette smoking, which is causally related to chronic obstructive pulmonary disease (COPD) and lung cancer. To date, there have been few large-scale, combined analyses of DNA methylation and gene expression and their interrelations with lung diseases. Results: We performed an epigenome-wide association study of whole blood gene expression in ~ 6000 individuals from four cohorts. We discovered and replicated numerous CpGs associated with the expression of cis genes within 500 kb of each CpG, with 148 to 1,741 cis CpG-transcript pairs identified across cohorts. We found that the closer a CpG resided to a transcription start site, the larger its effect size, and that 36% of cis CpG-transcript pairs share the same causal genetic variant. Mendelian randomization analyses revealed that hypomethylation and lower expression of CHRNA5, which encodes a smoking-related nicotinic receptor, are causally linked to increased risk of COPD and lung cancer. This putatively causal relationship was further validated in lung tissue data. Conclusions: Our results provide a large and comprehensive association study of whole blood DNA methylation with gene expression. Expression platform differences rather than population differences are critical to the replication of cis CpG-transcript pairs. The low reproducibility of trans CpG-transcript pairs suggests that DNA methylation regulates nearby rather than remote gene expression. The putatively causal roles of methylation and expression of CHRNA5 in relation to COPD and lung cancer provide evidence for a mechanistic link between patterns of smoking-related epigenetic variation and lung diseases, and highlight potential therapeutic targets for lung diseases and smoking cessation. [ABSTRACT FROM AUTHOR]

Background: The discovery of robust and trans-ethnically replicated DNA methylation markers of metabolic phenotypes, has hinted at a potential role of epigenetic mechanisms in lipid metabolism. However, DNA methylation and the lipid compositions and lipid concentrations of lipoprotein sizes have been scarcely studied. Here, we present an epigenome-wide association study (EWAS) (N = 5414 total) of mostly lipid-related metabolic measures, including a fine profiling of lipoproteins. As lipoproteins are the main players in the different stages of lipid metabolism, examination of epigenetic markers of detailed lipoprotein features might improve the diagnosis, prognosis, and treatment of metabolic disturbances. Results: We conducted an EWAS of leukocyte DNA methylation and 226 metabolic measurements determined by nuclear magnetic resonance spectroscopy in the population-based KORA F4 study (N = 1662) and replicated the results in the LOLIPOP, NFBC1966, and YFS cohorts (N = 3752). Follow-up analyses in the discovery cohort included investigations into gene transcripts, metabolic-measure ratios for pathway analysis, and disease endpoints. We identified 161 associations (p value < 4.7 × 10−10), covering 16 CpG sites at 11 loci and 57 metabolic measures. Identified metabolic measures were primarily medium and small lipoproteins, and fatty acids. For apolipoprotein B-containing lipoproteins, the associations mainly involved triglyceride composition and concentrations of cholesterol esters, triglycerides, free cholesterol, and phospholipids. All associations for HDL lipoproteins involved triglyceride measures only. Associated metabolic measure ratios, proxies of enzymatic activity, highlight amino acid, glucose, and lipid pathways as being potentially epigenetically implicated. Five CpG sites in four genes were associated with differential expression of transcripts in blood or adipose tissue. CpG sites in ABCG1 and PHGDH showed associations with metabolic measures, gene transcription, and metabolic measure ratios and were additionally linked to obesity or previous myocardial infarction, extending previously reported observations. Conclusion: Our study provides evidence of a link between DNA methylation and the lipid compositions and lipid concentrations of different lipoprotein size subclasses, thus offering in-depth insights into well-known associations of DNA methylation with total serum lipids. The results support detailed profiling of lipid metabolism to improve the molecular understanding of dyslipidemia and related disease mechanisms. [ABSTRACT FROM AUTHOR]

DNA methylation may be one of the mechanisms by which alcohol consumption is associated with the risk of disease. We conducted a large-scale, cross-sectional, genome-wide DNA methylation association study of alcohol consumption and a longitudinal analysis of repeated measurements taken several years apart. Using the Illumina HumanMethylation450 BeadChip, DNA methylation was measured in blood samples from 5606 Melbourne Collaborative Cohort Study (MCCS) participants. For 1088 of them, these measures were repeated using blood samples collected a median of 11 years later. Associations between alcohol intake and blood DNA methylation were assessed using linear mixed-effects regression models. Independent data from the London Life Sciences Prospective Population (LOLIPOP) (N = 4042) and Cooperative Health Research in the Augsburg Region (KORA) (N = 1662) cohorts were used to replicate associations discovered in the MCCS. Cross-sectional analyses identified 1414 CpGs associated with alcohol intake at P < 10-7 , 1243 of which had not been reported previously. Of these novel associations, 1078 were replicated (P < .05) using LOLIPOP and KORA data. Using the MCCS data, we also replicated 403 of 518 previously reported associations. Interaction analyses suggested that associations were stronger for women, non-smokers, and participants genetically predisposed to consume less alcohol. Of the 1414 CpGs, 530 were differentially methylated (P < .05) in former compared with current drinkers. Longitudinal associations between the change in alcohol intake and the change in methylation were observed for 513 of the 1414 cross-sectional associations. Our study indicates that alcohol intake is associated with widespread changes in DNA methylation across the genome. Longitudinal analyses showed that the methylation status of alcohol-associated CpGs may change with alcohol consumption changes in adulthood. [ABSTRACT FROM AUTHOR]

With an estimated prevalence of 463 million affected, type 2 diabetes represents a major challenge to health care systems worldwide. Analyzing the plasma proteomes of individuals with type 2 diabetes may illuminate hitherto unknown functional mechanisms underlying disease pathology. We assessed the associations between type 2 diabetes and >1,000 plasma proteins in the Cooperative Health Research in the Region of Augsburg (KORA) F4 cohort (n = 993, 110 cases), with subsequent replication in the third wave of the Nord-Trøndelag Health Study (HUNT3) cohort (n = 940, 149 cases). We computed logistic regression models adjusted for age, sex, BMI, smoking status, and hypertension. Additionally, we investigated associations with incident type 2 diabetes and performed two-sample bidirectional Mendelian randomization (MR) analysis to prioritize our results. Association analysis of prevalent type 2 diabetes revealed 24 replicated proteins, of which 8 are novel. Proteins showing association with incident type 2 diabetes were aminoacylase-1, growth hormone receptor, and insulin-like growth factor-binding protein 2. Aminoacylase-1 was associated with both prevalent and incident type 2 diabetes. MR analysis yielded nominally significant causal effects of type 2 diabetes on cathepsin Z and rennin, both known to have roles in the pathophysiological pathways of cardiovascular disease, and of sex hormone-binding globulin on type 2 diabetes. In conclusion, our high-throughput proteomics study replicated previously reported type 2 diabetes-protein associations and identified new candidate proteins possibly involved in the pathogenesis of type 2 diabetes. [ABSTRACT FROM AUTHOR]