The prenatal environment may program health and disease susceptibility via epigenetic mechanisms. We evaluated associations of maternal trimester-specific intake of micronutrients with global DNA methylation (%5mC) and 5-hydroxymethylation (%5hmC) at birth in cord blood and tested for persistence into childhood. We quantified global %5mC and %5hmC in cord blood cells (n = 434) and in leukocytes collected in early (n = 108) and mid-childhood (n = 390) from children in Project Viva, a pre-birth cohort from Boston, MA. Validated food frequency questionnaires estimated maternal first- and second-trimester intakes of vitamin B2, vitamin B6, vitamin B12, folate, betaine, choline, methionine, iron, and zinc. Mean (SD) cord blood %5mC and %5hmC was 5.62% (2.04) and 0.25% (0.15), respectively. Each μg increase in first-trimester B12 intake was associated with 0.002 lower %5hmC in cord blood (95% CI: −0.005, −0.0003), and this association persisted in early childhood (β = −0.007; 95% CI: −0.01, −0.001) but not mid-childhood. Second-trimester iron (mg) was associated with 0.01 lower %5mC (95% CI: −0.02, −0.002) and 0.001 lower %5hmC (95% CI: −0.01, −0.00001) in cord blood only. Increased second-trimester zinc (mg) intake was associated with 0.003 greater %5hmC in early childhood (β = 0.003; 95% CI: 0.0004, 0.006). Second-trimester folate was positively associated with %5hmC in early childhood only (β = 0.08, 95% CI: 0.003, 0.16). Associations did not survive multiple testing adjustment; future replication is needed. Trimester-specific nutrients may impact various sensitive windows of epigenetic programming some with lasting effects in childhood. Further research is needed to understand the role of gene-specific epigenetic changes and how global DNA methylation measures relate to child health.

An isotope dilution model for partitioning phenylalanine and tyrosine uptake by the liver of the lactating dairy cow is constructed and solved in the steady state. An original ten-pool model is adopted and solved by cleaving it into two five-pool sub-models, one representing phenylalanine and the other tyrosine. If assumptions are made, model solution permits calculation of the rate of phenylalanine and tyrosine uptake from portal vein and hepatic arterial blood supply, hydroxylation, and synthesis and degradation of constitutive protein. The model requires the measurement of plasma flow rate through the liver in combination with amino acid concentrations and plateau isotopic enrichments in arterial and portal and hepatic vein plasma during a constant infusion of [1-13C]phenylalanine and [2,3,5,6-2H]tyrosine tracers. It also requires estimates of the rate of oxidation and protein export secretion. Analysis of measurement errors in experimental enrichments and infusion rates on model solutions indicated that accurate values of the intracellular and extracellular enrichments are central to minimising errors in the calculated flows. Solving the model by cleaving into two five-pool schemes rather than solving the ten-pool scheme directly is preferred as there appears to be less compounding of errors and the results consistently appear to be more biologically feasible. The model provides a means for assessing the impact of hepatic metabolism on amino acid availability to peripheral tissues such as the mammary gland.

Mobile health technology is an emerging tool in interstage home monitoring for infants with single ventricle heart disease or biventricular shunt-dependent defects. This study sought to describe adherence to mobile health monitoring and identify factors and outcomes associated with adherence to mobile health monitoring. This was a retrospective, single-institution study of infants who were followed in a mobile health-based interstage home monitoring programme between February 2016 and October 2020. The analysis included 105 infants and subjects were grouped by frequency of adherence to mobile health monitoring. Within the study cohort, 16 (15.2%) had 0% adherence, 25 (23.8%) had <50% adherence, and 64 (61.0%) had >50% adherence. The adherent groups had a higher percentage of infants who were male (p = 0.02), white race (p < 0.01), non-Hispanic or non-Latinx ethnicity (p < 0.01) and had mothers with primary English fluency (p < 0.01), married marital status (p < 0.01), and a prenatal diagnosis of faetal cardiac disease (p = 0.03). Adherent groups also had a higher percentage of infants with non-Medicaid primary insurance (p < 0.01) and residence in a neighbourhood with a higher median household income (p < 0.04). Frequency of adherence was not associated with interstage mortality, unplanned cardiac reinterventions, or hospital readmissions. Impact of mobile health interstage home monitoring on caregiver stress as well as use of multi-language, low literacy, affordable mobile health options for interstage home monitoring warrant further investigation.

Phenylalanine (PHE) and to a lesser extent TYR are two commonly used amino acid tracers for measuring protein metabolism in a variety of species and tissues. The model examined in this paper was developed to resolve trans-organ and stable isotope dilution data collected from experiments with lactating dairy cows using these tracers. Two methods of solving the model, i.e. as two four-pool submodels, one representing PHE and the other TYR, or as an integrated eight-pool model, are investigated and the alternative solutions are contrasted. Solving the model as the two four-pool submodels rather than the integrated 8-pool model is preferred as the equations are slightly simpler and their application less susceptible to any compounding of measurement errors. The data used to illustrate the model were taken from experiments conducted to investigate the effects of high and low protein diets on the partitioning of PHE and TYR between milk protein synthesis and other metabolic fates by the mammary gland.

ABSTRACT IMPACT: Recognizing Interdisciplinary Collaborative Research in Promotion and Tenure Processes OBJECTIVES/GOALS: Academic institutions have traditionally focused on individual achievements for promotion. We present our effort on identifying and measuring attitudes on promotion and tenure (PT) criteria that values and rewards interdisciplinary research (IR). We have developed a toolkit to facilitate the recognition of IR in PT processes. METHODS/STUDY POPULATION: Our group reviewed appointment, promotion and tenure (APT) policies from each of the six Health Science Schools and the College of Engineering at the University of Washington (UW) to assess language of objective criteria and attributes of IR to guide APT committees in the evaluation of interdisciplinary researchers. We surveyed faculty about their attitudes relating to IR within the context of promotion and tenure. Interviews of department chairs and administrators about institutional policies and infrastructure that supports or inhibits IR, and current best practices, were conducted. We have developed toolkits for junior faculty, department chairs, external reviewers, and APT committees to facilitate rewarding IR at promotion. RESULTS/ANTICIPATED RESULTS: Review of APT policies found criteria that recognizes IR for APT in three schools. 118 faculty responded to the survey (44% Professor, 26% Associate, and 37% eligible for APT committees). The majority of faculty reported they were currently conducting IR (95%), considered IR important (98%), and believed the UW faculty code should encourage IR (85%). Although a vast majority considered their units supportive of IR (>80%), less than half (43%) reported that their APT criteria provided examples that included participation in IR. Our survey also found that APT committees were challenged about best practices to reward IR, APT external reviewers struggle to evaluate individual vs team contributions, and individual faculty are challenged to describe contributions for APT within context of an interdisciplinary team. DISCUSSION/SIGNIFICANCE OF FINDINGS: IR is conducted and valued by UW faculty; however, current structures, policies, and APT code do not facilitate IR for promotion and tenure. We have developed a toolkit for promotion-eligible faculty, chairs, external reviewers, and APT committees to facilitate IR. Our goal is to modify UW faculty code and unit APT criteria to recognize and reward IR.

Susceptibility to infection such as SARS-CoV-2 may be influenced by host genotype. TwinsUK volunteers (n = 3261) completing the C-19 COVID-19 symptom tracker app allowed classical twin studies of COVID-19 symptoms, including predicted COVID-19, a symptom-based algorithm to predict true infection, derived from app users tested for SARS-CoV-2. We found heritability of 49% (32−64%) for delirium; 34% (20−47%) for diarrhea; 31% (8−52%) for fatigue; 19% (0−38%) for anosmia; 46% (31−60%) for skipped meals and 31% (11−48%) for predicted COVID-19. Heritability estimates were not affected by cohabiting or by social deprivation. The results suggest the importance of host genetics in the risk of clinical manifestations of COVID-19 and provide grounds for planning genome-wide association studies to establish specific genes involved in viral infectivity and the host immune response.

The elimination of unwanted catch in mixed species fisheries is technically challenging given the complexity of fish behaviour within nets. Most approaches to date have employed technologies that modify the nets themselves or use physical sorting grids within the gear. There is currently increasing interest in the use of artificial light to either deter fish from entering the net, or to enhance their escapement from within the net. Here, we evaluated the differences in catch retained in a standard otter trawl, relative to the same gear fitted with a square mesh panel, or a square mesh panel fitted with LEDs. We found that the selectivity of the gear differed depending on water depth. When using a square mesh panel in shallow depths of 29–40 m the unwanted bycatch of whiting and haddock was reduced by 86% and 58% respectively. In deep, darker water (45–95 m), no change in catch was observed in the square-mesh panel treatment, however when LEDs were added to the square-mesh panel, haddock and flatfish catches were reduced by 47% and 25% respectively. These findings demonstrate the potential to improve the performance of bycatch reduction devices through the addition of light devices to enhance selectivity. The results also highlight species-specific and site-specific differences in the performance of bycatch reduction devices, and hence a more adaptive approach to reduce bycatch is probably required to maximize performance.

TwinsUK is the largest cohort of community-dwelling adult twins in the UK. The registry comprises over 14,000 volunteer twins (14,838 including mixed, single and triplets); it is predominantly female (82%) and middle-aged (mean age 59). In addition, over 1800 parents and siblings of twins are registered volunteers. During the last 27 years, TwinsUK has collected numerous questionnaire responses, physical/cognitive measures and biological measures on over 8500 subjects. Data were collected alongside four comprehensive phenotyping clinical visits to the Department of Twin Research and Genetic Epidemiology, King’s College London. Such collection methods have resulted in very detailed longitudinal clinical, biochemical, behavioral, dietary and socioeconomic cohort characterization; it provides a multidisciplinary platform for the study of complex disease during the adult life course, including the process of healthy aging. The major strength of TwinsUK is the availability of several ‘omic’ technologies for a range of sample types from participants, which includes genomewide scans of single-nucleotide variants, next-generation sequencing, metabolomic profiles, microbiomics, exome sequencing, epigenetic markers, gene expression arrays, RNA sequencing and telomere length measures. TwinsUK facilitates and actively encourages sharing the ‘TwinsUK’ resource with the scientific community — interested researchers may request data via the TwinsUK website (http://twinsuk.ac.uk/resources-for-researchers/access-our-data/) for their own use or future collaboration with the study team. In addition, further cohort data collection is planned via the Wellcome Open Research gateway (https://wellcomeopenresearch.org/gateways). The current article presents an up-to-date report on the application of technological advances, new study procedures in the cohort and future direction of TwinsUK.

Several research teams have previously traced patterns of emerging conduct problems (CP) from early or middle childhood. The current study expands on this previous literature by using a genetically-informed, experimental, and long-term longitudinal design to examine trajectories of early-emerging conduct problems and early childhood discriminators of such patterns from the toddler period to adolescence. The sample represents a cohort of 731 toddlers and diverse families recruited based on socioeconomic, child, and family risk, varying in urbanicity and assessed on nine occasions between ages 2 and 14. In addition to examining child, family, and community level discriminators of patterns of emerging conduct problems, we were able to account for genetic susceptibility using polygenic scores and the study's experimental design to determine whether random assignment to the Family Check-Up (FCU) discriminated trajectory groups. In addition, in accord with differential susceptibility theory, we tested whether the effects of the FCU were stronger for those children with higher genetic susceptibility. Results augmented previous findings documenting the influence of child (inhibitory control [IC], gender) and family (harsh parenting, parental depression, and educational attainment) risk. In addition, children in the FCU were overrepresented in the persistent low versus persistent high CP group, but such direct effects were qualified by an interaction between the intervention and genetic susceptibility that was consistent with differential susceptibility. Implications are discussed for early identification and specifically, prevention efforts addressing early child and family risk.

The search for life in the Universe is a fundamental problem of astrobiology and modern science. The current progress in the detection of terrestrial-type exoplanets has opened a new avenue in the characterization of exoplanetary atmospheres and in the search for biosignatures of life with the upcoming ground-based and space missions. To specify the conditions favourable for the origin, development and sustainment of life as we know it in other worlds, we need to understand the nature of global (astrospheric), and local (atmospheric and surface) environments of exoplanets in the habitable zones (HZs) around G-K-M dwarf stars including our young Sun. Global environment is formed by propagated disturbances from the planet-hosting stars in the form of stellar flares, coronal mass ejections, energetic particles and winds collectively known as astrospheric space weather. Its characterization will help in understanding how an exoplanetary ecosystem interacts with its host star, as well as in the specification of the physical, chemical and biochemical conditions that can create favourable and/or detrimental conditions for planetary climate and habitability along with evolution of planetary internal dynamics over geological timescales. A key linkage of (astro)physical, chemical and geological processes can only be understood in the framework of interdisciplinary studies with the incorporation of progress in heliophysics, astrophysics, planetary and Earth sciences. The assessment of the impacts of host stars on the climate and habitability of terrestrial (exo)planets will significantly expand the current definition of the HZ to the biogenic zone and provide new observational strategies for searching for signatures of life. The major goal of this paper is to describe and discuss the current status and recent progress in this interdisciplinary field in light of presentations and discussions during the NASA Nexus for Exoplanetary System Science funded workshop ‘Exoplanetary Space Weather, Climate and Habitability’ and to provide a new roadmap for the future development of the emerging field of exoplanetary science and astrobiology.

Solar coronal dimmings have been observed extensively in the past two decades and are believed to have close association with coronal mass ejections (CMEs). Recent study found that coronal dimming is the only signature that could differentiate powerful flares that have CMEs from those that do not. Therefore, dimming might be one of the best candidates to observe the stellar CMEs on distant Sun-like stars. In this study, we investigate the possibility of using coronal dimming as a proxy to diagnose stellar CMEs. By simulating a realistic solar CME event and corresponding coronal dimming using a global magnetohydrodynamics model (AWSoM: Alfvén-wave Solar Model), we first demonstrate the capability of the model to reproduce solar observations. We then extend the model for simulating stellar CMEs by modifying the input magnetic flux density as well as the initial magnetic energy of the CME flux rope. Our result suggests that with improved instrument sensitivity, it is possible to detect the coronal dimming signals induced by the stellar CMEs.

Dicationic cobalt(II) complexes of the type [Co(fterpy)2]c(X)2·nH2O·mCH3OH (fterpy = 4′-(2-furyl)-2,2′:6′,2″-terpyridine; 1: X = PF6-, n = 1.5, m = 0; 2: X = ClO4-, n = 1, m = 1) have been isolated using self-assembly method and characterized by various spectroscopic techniques. In crystalline states both compounds exhibit gradual and incomplete spin crossover (SCO) behaviour in the temperature range 2-320 K. Various spin states of cobalt(II) in 1 have been confirmed by crystallographic evidences at 150 K and 293 K. A variation in counter anions and solvent molecules from 1 to 2 substantially improves the cooperativity among the spin active metal centres and thereby changing the nature of SCO behaviour.