The Eukaryotic Proteome Is Shaped by E3 Ubiquitin Ligases Targeting C-Terminal Degrons.

Degrons are minimal elements that mediate the interaction of proteins with degradation machineries to promote proteolysis. Despite their central role in proteostasis, the number of known degrons remains small, and a facile technology to characterize them is lacking. Using a strategy combining global protein stability (GPS) profiling with a synthetic human peptidome, we identify thousands of peptides containing degron activity. Employing CRISPR screening, we establish that the stability of many proteins is regulated through degrons located at their C terminus. We characterize eight Cullin-RING E3 ubiquitin ligase (CRL) complex adaptors that regulate C-terminal degrons, including six CRL2 and two CRL4 complexes, and computationally implicate multiple non-CRLs in end recognition. Proteome analysis revealed that the C termini of eukaryotic proteins are depleted for C-terminal degrons, suggesting an E3-ligase-dependent modulation of proteome composition. Thus, we propose that a series of "C-end rules" operate to govern protein stability and shape the eukaryotic proteome.

Ubiquitin-independent proteasomal degradation driven by C-degron pathways.

Although most eukaryotic proteins are targeted for proteasomal degradation by ubiquitination, a subset have been demonstrated to undergo ubiquitin-independent proteasomal degradation (UbInPD). However, little is known about the molecular mechanisms driving UbInPD and the degrons involved. Utilizing the GPS-peptidome approach, a systematic method for degron discovery, we found thousands of sequences that promote UbInPD; thus, UbInPD is more prevalent than currently appreciated. Furthermore, mutagenesis experiments revealed specific C-terminal degrons required for UbInPD. Stability profiling of a genome-wide collection of human open reading frames identified 69 full-length proteins subject to UbInPD. These included REC8 and CDCA4, proteins which control proliferation and survival, as well as mislocalized secretory proteins, suggesting that UbInPD performs both regulatory and protein quality control functions. In the context of full-length proteins, C termini also play a role in promoting UbInPD. Finally, we found that Ubiquilin family proteins mediate the proteasomal targeting of a subset of UbInPD substrates.

Elucidation of E3 ubiquitin ligase specificity through proteome-wide internal degron mapping.

The ubiquitin-proteasome system plays a critical role in biology by regulating protein degradation. Despite their importance, precise recognition specificity is known for a few of the 600 E3s. Here, we establish a two-pronged strategy for identifying and mapping critical residues of internal degrons on a proteome-scale in HEK-293T cells. We employ global protein stability profiling combined with machine learning to identify 15,800 peptides likely to contain sequence-dependent degrons. We combine this with scanning mutagenesis to define critical residues for over 5,000 predicted degrons. Focusing on Cullin-RING ligase degrons, we generated mutational fingerprints for 219 degrons and developed DegronID, a computational algorithm enabling the clustering of degron peptides with similar motifs. CRISPR analysis enabled the discovery of E3-degron pairs, of which we uncovered 16 pairs that revealed extensive degron variability and structural determinants. We provide the visualization of these data on the public DegronID data browser as a resource for future exploration.

The corepressors GPS2 and SMRT control enhancer and silencer remodeling via eRNA transcription during inflammatory activation of macrophages.

While the role of transcription factors and coactivators in controlling enhancer activity and chromatin structure linked to gene expression is well established, the involvement of corepressors is not. Using inflammatory macrophage activation as a model, we investigate here a corepressor complex containing GPS2 and SMRT both genome-wide and at the Ccl2 locus, encoding the chemokine CCL2 (MCP-1). We report that corepressors co-occupy candidate enhancers along with the coactivators CBP (H3K27 acetylase) and MED1 (mediator) but act antagonistically by repressing eRNA transcription-coupled H3K27 acetylation. Genome editing, transcriptional interference, and cistrome analysis reveals that apparently related enhancer and silencer elements control Ccl2 transcription in opposite ways. 4C-seq indicates that corepressor depletion or inflammatory signaling functions mechanistically similarly to trigger enhancer activation. In ob/ob mice, adipose tissue macrophage-selective depletion of the Ccl2 enhancer-transcribed eRNA reduces metaflammation. Thus, the identified corepressor-eRNA-chemokine pathway operates in vivo and suggests therapeutic opportunities by targeting eRNAs in immuno-metabolic diseases.

Mitochondrial Retrograde Signaling in Mammals Is Mediated by the Transcriptional Cofactor GPS2 via Direct Mitochondria-to-Nucleus Translocation.

As most of the mitochondrial proteome is encoded in the nucleus, mitochondrial functions critically depend on nuclear gene expression and bidirectional mito-nuclear communication. However, mitochondria-to-nucleus communication pathways in mammals are incompletely understood. Here, we identify G-Protein Pathway Suppressor 2 (GPS2) as a mediator of mitochondrial retrograde signaling and a transcriptional activator of nuclear-encoded mitochondrial genes. GPS2-regulated translocation from mitochondria to nucleus is essential for the transcriptional activation of a nuclear stress response to mitochondrial depolarization and for supporting basal mitochondrial biogenesis in differentiating adipocytes and brown adipose tissue (BAT) from mice. In the nucleus, GPS2 recruitment to target gene promoters regulates histone H3K9 demethylation and RNA POL2 activation through inhibition of Ubc13-mediated ubiquitination. These findings, together, reveal an additional layer of regulation of mitochondrial gene transcription, uncover a direct mitochondria-nuclear communication pathway, and indicate that GPS2 retrograde signaling is a key component of the mitochondrial stress response in mammals.

SkyPole-A method for locating the north celestial pole from skylight polarization patterns.

True north can be determined on Earth by three means: magnetic compasses, stars, and via the global navigation satellite systems (GNSS), each of which has its own drawbacks. GNSS are sensitive to jamming and spoofing, magnetic compasses are vulnerable to magnetic interferences, and the stars can be used only at night with a clear sky. As an alternative to these methods, nature-inspired navigational cues are of particular interest. Celestial polarization, which is used by insects such as Cataglyphis ants, can provide useful directional cues. Migrating birds calibrate their magnetic compasses by observing the celestial rotation at night. By combining these cues, we have developed a bioinspired optical method for finding the celestial pole during the daytime. This method, which we have named SkyPole, is based on the rotation of the skylight polarization pattern. A polarimetric camera was used to measure the degree of skylight polarization rotating with the Sun. Image difference processes were then applied to the time-varying measurements in order to determine the north celestial pole's position and thus the observer's latitude and bearing with respect to the true north.

Physics-guided self-supervised learning: Demonstration for generalized RF pulse design.

PURPOSE: To introduce a new method for generalized RF pulse design using physics-guided self-supervised learning (GPS), which uses the Bloch equations as the guiding physics model. THEORY AND METHODS: The GPS framework consists of a neural network module and a physics module, where the physics module is a Bloch simulator for MRI applications. For RF pulse design, the neural network module maps an input target profile to an RF pulse, which is subsequently loaded into the physics module. Through the supervision of the physics module, the neural network module designs an RF pulse corresponding to the target profile. GPS was applied to design 1D selective, B 1 $$ {B}_1 $$ -insensitive, saturation, and multidimensional RF pulses, each conventionally requiring dedicated design algorithms. We further demonstrate our method's flexibility and versatility by compensating for experimental and scanner imperfections through online adaptation. RESULTS: Both simulations and experiments show that GPS can design a variety of RF pulses with corresponding profiles that agree well with the target input. Despite these verifications, GPS-designed pulses have unique differences compared to conventional designs, such as achieving B 1 $$ {B}_1 $$ -insensitivity using different mechanisms and using non-sampled regions of the conventional design to lower its peak power. Experiments, both ex vivo and in vivo, further verify that it can also be used for online adaptation to correct system imperfections, such as B 0 $$ {B}_0 $$ / B 1 + $$ {B}_1^{+} $$ inhomogeneity. CONCLUSION: This work demonstrates the generalizability, versatility, and flexibility of the GPS method for designing RF pulses and showcases its utility in several applications.

GPS2 ameliorates cigarette smoking-induced pulmonary vascular remodeling by modulating the ras-Raf-ERK axis.

BACKGROUND: Mitogen-activated protein kinase (MAPK)signaling-mediated smoking-associated pulmonary vascular remodeling (PVR) plays an important role in the pathogenesis of group 3 pulmonary hypertension (PH). And G protein pathway suppressor 2 (GPS2) could suppress G-protein signaling such as Ras and MAPK, but its role in cigarette smoking -induced PVR (CS-PVR) is unclear. METHODS: An in vivo model of smoke-exposed rats was constructed to assess the role of GPS2 in smoking-induced PH and PVR. In vitro, the effects of GPS2 overexpression and silencing on the function of human pulmonary arterial smooth cells (HPASMCs) and the underlying mechanisms were explored. RESULTS: GPS2 expression was downregulated in rat pulmonary arteries (PAs) and HPASMCs after CS exposure. More importantly, CS-exposed rats with GPS2 overexpression had lower right ventricular systolic pressure (RVSP), right ventricular hypertrophy index (RVHI), and wall thickness (WT%) than those without. And enhanced proliferation and migration of HPASMCs induced by cigarette smoking extract (CSE) can be evidently inhibited by overexpressed GPS2. Besides, GPS2siRNA significantly enhanced the proliferation, and migration of HPASMCs as well as activated Ras and Raf/ERK signaling, while these effects were inhibited by zoledronic acid (ZOL). In addition, GPS2 promoter methylation level in rat PAs and HPASMCs was increased after CS exposure, and 5-aza-2-deoxycytidine (5-aza) inhibited CSE-induced GPS2 hypermethylation and downregulation in vitro. CONCLUSIONS: GPS2 overexpression could improve the CS-PVR, suggesting that GPS2 might serve as a novel therapeutic target for PH-COPD in the future.

Key Grazing Behaviours of Beef Cattle Identify Specific Genotypes of the Glutamate Metabotropic Receptor 5 Gene (GRM5).

Genotype-phenotype associations between the bovine genome and grazing behaviours measured over time and across contexts have been reported in the past decade, with these suggesting the potential for genetic control over grazing personalities in beef cattle. From the large array of metrics used to describe grazing personality behaviours (GP-behaviours), it is still unclear which ones are linked to specific genes. Our prior observational study has reported associations and trends towards associations between genotypes of the glutamate metabotropic receptor 5 gene (GRM5) and four GP-behaviours, yet the unbalanced representation of GRM5 genotypes occurring in observational studies may have limited the ability to detect associations. Here, we applied a subsampling technique to create a genotypically-balanced dataset in a quasi-manipulative experiment with free ranging cows grazing in steep and rugged terrain of New Zealand's South Island. Using quadratic discriminant analysis, two combinations of eleven GP-behaviours (and a total of fifteen behaviours) were selected to build an exploration model and an elevation model, respectively. Both models achieved ∼ 86% accuracy in correctly discriminating cows' GRM5 genotypes with the training dataset, and the exploration model achieved 85% correct genotype prediction of cows from a testing dataset. Our study suggests a potential pleiotropic effect, with GRM5 controlling multiple grazing behaviours, and with implications for the grazing of steep and rugged grasslands. The study highlights the importance of grazing behavioural genetics in cattle and the potential use of GRM5 markers to select individuals with desired grazing personalities and built herds that collectively utilize steep and rugged rangelands sustainably.

Inhibition of K63 ubiquitination by G-Protein pathway suppressor 2 (GPS2) regulates mitochondria-associated translation.

G-Protein Pathway Suppressor 2 (GPS2) is an inhibitor of non-proteolytic K63 ubiquitination mediated by the E2 ubiquitin-conjugating enzyme Ubc13. Previous studies have associated GPS2-mediated restriction of ubiquitination with the regulation of insulin signaling, inflammatory responses and mitochondria-nuclear communication across different tissues and cell types. However, a detailed understanding of the targets of GPS2/Ubc13 activity is lacking. Here, we have dissected the GPS2-regulated K63 ubiquitome in mouse embryonic fibroblasts and human breast cancer cells, unexpectedly finding an enrichment for proteins involved in RNA binding and translation on the outer mitochondrial membrane. Validation of selected targets of GPS2-mediated regulation, including the RNA-binding protein PABPC1 and translation factors RPS1, RACK1 and eIF3M, revealed a mitochondrial-specific strategy for regulating the translation of nuclear-encoded mitochondrial proteins via non-proteolytic ubiquitination. Removal of GPS2-mediated inhibition, either via genetic deletion or stress-induced nuclear translocation, promotes the import-coupled translation of selected mRNAs leading to the increased expression of an adaptive antioxidant program. In light of GPS2 role in nuclear-mitochondria communication, these findings reveal an exquisite regulatory network for modulating mitochondrial gene expression through spatially coordinated transcription and translation.

Comparing malaria risk exposure in rural Cambodia population using GPS tracking and questionnaires.

BACKGROUND: The Great Mekong Subregion has attained a major decline in malaria cases and fatalities over the last years, but residual transmission hotspots remain, supposedly fueled by forest workers and migrant populations. This study aimed to: (i) characterize the fine-scale mobility of forest-goers and understand links between their daily movement patterns and malaria transmission, using parasites detection via real time polymerase chain reaction (RT PCR) and the individual exposure to Anopheles bites by quantification of anti-Anopheles saliva antibodies via enzyme-linked immunosorbent assay; (ii) assess the concordance of questionnaires and Global Positioning System (GPS) data loggers for measuring mobility. METHODS: Two 28 day follow-ups during dry and rainy seasons, including a GPS tracking, questionnaires and health examinations, were performed on male forest goers representing the population at highest risk of infection. Their time spent in different land use categories and demographic data were analyzed in order to understand the risk factors driving malaria in the study area. RESULTS: Malaria risk varied with village forest cover and at a resolution of only a few kilometers: participants from villages outside the forest had the highest malaria prevalence compared to participants from forest fringe's villages. The time spent in a specific environment did not modulate the risk of malaria, in particular the time spent in forest was not associated with a higher probability to detect malaria among forest-goers. The levels of antibody response to Anopheles salivary peptide among participants were significantly higher during the rainy season, in accordance with Anopheles mosquito density variation, but was not affected by sociodemographic and mobility factors. The agreement between GPS and self-reported data was only 61.9% in reporting each kind of visited environment. CONCLUSIONS: In a context of residual malaria transmission which was mainly depicted by P. vivax asymptomatic infections, the implementation of questionnaires, GPS data-loggers and quantification of anti-saliva Anopheles antibodies on the high-risk group were not powerful enough to detect malaria risk factors associated with different mobility behaviours or time spent in various environments. The joint implementation of GPS trackers and questionnaires allowed to highlight the limitations of both methodologies and the benefits of using them together. New detection and follow-up strategies are still called for.

To breed or not to breed: Territory occupancy is predicted by reproductive performance and habitat heterogeneity.

Species life history and anthropogenic influence are important drivers of population performance and viability in human-dominated ecosystems. How these factors affect habitat selection and occupancy in long-lived species is an important topic for their conservation. Long-term datasets are needed for establishing the underlying drivers of this process. In this 22 year-long study, we conducted annual surveys of Bonelli's eagle in the east of the Iberian Peninsula. During this period, 42.8% of the known territories remained unoccupied. Territories with a higher likelihood of raising two chicks over time were stable, evidenced by a lower coefficient of variation in productivity, and were more likely to remain occupied. Moreover, territories with lower habitat diversity, dominated by coniferous forest or agricultural fields, and those located further away from the coast and at higher altitudes showed lower rates of occupancy (i.e., unoccupied >3 consecutive years). To validate these associations, we monitored space use of 22 individuals equipped with Global Positioning System/Global System for Mobile (GPS/GSM) transmitters, which confirmed that eagles selected for open habitats (mainly scrublands and transitional woodland-scrubs) intermixed with forest areas within their home ranges. In contrast, individuals avoided areas dominated by agricultural, urban, and continuous forests for breeding in line with the observations for unoccupied territories. Our results highlight the important interplay between natural and anthropogenic factors, which also have important implications for other raptor species. Preservation of the most productive territories and the re-occupancy of unoccupied territories along with reducing threats in the preferred habitats are fundamental actions that should be taken immediately to sustain viable populations. Potential management actions include enhancing natural prey density through habitat restoration and conservation, mitigating threats and reducing mortality risks due to power lines, fences, poisoning, and maintaining habitat heterogeneity important to eagles' hunting activities.

Human access constrains optimal foraging and habitat availability in an avian generalist.

Animals balance costs of antipredator behaviors with resource acquisition to minimize hunting and other mortality risks and maximize their physiological condition. This inherent trade-off between forage abundance, its quality, and mortality risk is intensified in human-dominated landscapes because fragmentation, habitat loss, and degradation of natural vegetation communities is often coupled with artificially enhanced vegetation (i.e., food plots), creating high-risk, high-reward resource selection decisions. Our goal was to evaluate autumn-winter resource selection trade-offs for an intensively hunted avian generalist. We hypothesized human access was a reliable cue for hunting predation risk. Therefore, we predicted resource selection patterns would be spatiotemporally dependent upon levels of access and associated perceived risk. Specifically, we evaluated resource selection of local-scale flights between diel periods for 426 mallards (Anas platyrhynchos) relative to wetland type, forage quality, and differing levels of human access across hunting and nonhunting seasons. Mallards selected areas that prohibited human access and generally avoided areas that allowed access diurnally, especially during the hunting season. Mallards compensated by selecting for high-energy and greater quality foraging patches on allowable human access areas nocturnally when they were devoid of hunters. Postseason selection across human access gradients did not return to prehunting levels immediately, perhaps suggesting a delayed response to reacclimate to nonhunted activities and thus agreeing with the assessment mismatch hypothesis. Last, wetland availability and human access constrained selection for optimal natural forage quality (i.e., seed biomass and forage productivity) diurnally during preseason and hunting season, respectively; however, mallards were freed from these constraints nocturnally during hunting season and postseason periods. Our results suggest risk-avoidance of human accessible (i.e., hunted) areas is a primary driver of resource selection behaviors by mallards and could be a local to landscape-level process influencing distributions, instead of forage abundance and quality, which has long-been assumed by waterfowl conservation planners in North America. Broadly, even an avian generalist, well adapted to anthropogenic landscapes, avoids areas where hunting and human access are allowed. Future conservation planning and implementation must consider management for recreational access (i.e., people) equally important as foraging habitat management for wintering waterfowl.

Ontogeny of migration destination, route and timing in a partially migratory bird.

In migratory animals, the developmental period from inexperienced juveniles to breeding adults could be a key life stage in shaping population migration patterns. Nevertheless, the development of migration routines in early life remains underexplored. While age-related changes in migration routes and timing have been described in obligate migrants, most investigations into the ontogeny of partial migrants only focused on age-dependency of migration as a binary tactic (migrant or resident), and variations in routes and timing among individuals classified as 'migrants' is rarely considered. To fill this gap, we study the ontogeny of migration destination, route and timing in a partially migratory red kite (Milvus milvus) population. Using an extensive GPS-tracking dataset (292 fledglings and 38 adults, with 1-5 migrations tracked per individual), we studied how nine different migration characteristics changed with age and breeding status in migrant individuals, many of which become resident later in life. Individuals departed later from and arrived earlier at the breeding areas as they aged, resulting in a gradual prolongation of stay in the breeding area by 2 months from the first to the fifth migration. Individuals delayed southward migration in the year prior to territory acquirement, and they further delayed it after occupying a territory. Migration routes became more direct with age. Individuals were highly faithful to their wintering site. Migration distance shortened only slightly with age and was more similar among siblings than among unrelated individuals. The large gradual changes in northward and southward migrations suggest a high degree of plasticity in temporal characteristics during the developmental window. However, the high wintering site fidelity points towards large benefits of site familiarity, prompting spatial migratory plasticity to be expressed through a switch to residency. The contrasting patterns of trajectories of age-related changes between spatial and temporal migration characteristics might reflect different mechanisms underlying the expression of plasticity. Investigating such patterns among species along the entire spectrum of migration tactics would enable further understanding of the plastic responses exhibited by migratory species to rapid environmental changes.

Testing the information centre hypothesis in a multilevel society.

In various animal species conspecifics aggregate at sleeping sites. Such aggregations can act as information centres where individuals acquire up-to-date knowledge about their environment. In some species, communal sleeping sites comprise individuals from multiple groups, where each group maintains stable membership over time. We used GPS tracking to simultaneously record group movement in a population of wild vulturine guineafowl (Acryllium vulturinum) to investigate whether communal sleeping sites can facilitate the transfer of information among individuals across distinct groups. These birds live in large and stable groups that move both together and apart, often forming communal roosts containing up to five groups. We first test whether roosts provide the opportunity for individuals to acquire information from members of other groups by examining the spatial organization at roosts. The GPS data reveal that groups intermix, thereby providing an opportunity for individuals to acquire out-group information. We next conduct a field experiment to test whether naïve groups can locate novel food patches when co-roosting with knowledgeable groups. We find that co-roosting substantially increases the chances for the members of a naïve group to discover a patch known to individuals from other groups at the shared roost. Further, we find that the discovery of food patches by naïve groups subsequently shapes their space use and inter-group associations. We also draw on our long-term tracking to provide examples that demonstrate natural cases where communal roosting has preceded large-scale multi-group collective movements that extend into areas beyond the groups' normal ranges. Our findings support the extension of the information centre hypothesis to communal sleeping sites that consist of distinct social groups.

ExMove: An open-source toolkit for processing and exploring animal-tracking data in R.

Ongoing technological advances have led to a rapid increase in the number, type and scope of animal-tracking studies. In response, many software tools have been developed to analyse animal movement data. These tools generally focus on movement modelling, but the steps required to clean raw data files from different tracking devices have been largely ignored. Such pre-processing steps are often time-consuming and involve a steep learning curve but are crucial for the creation of high-quality, standardised and shareable data. Moreover, decisions made at this early stage can substantially influence subsequent analyses, and in the current age of reproducibility crisis, the transparency of this process is vital. Here we present an open-access, reproducible toolkit written in the programming language R for processing raw data files into a single cleaned data set for analyses and upload to online tracking databases (found here: https://github.com/ExMove/ExMove). The toolkit comprises well-documented and flexible code to facilitate data processing and user understanding, both of which can increase user confidence and improve the uptake of sharing open and reproducible code. Additionally, we provide an overview website (found here: https://exmove.github.io/) and a Shiny app to help users visualise tracking data and assist with parameter determination during data cleaning. The toolkit is generalisable to different data formats and device types, uses modern 'tidy coding' practices, and relies on a few well-maintained packages. Among these, we perform spatial manipulations using the package sf. Overall, by collating all required steps from data collection to archiving on open access databases into a single, robust pipeline, our toolkit provides a valuable resource for anyone conducting animal movement analyses and represents an important step towards increased standardisation and reproducibility in animal movement ecology.

Hidden rivals: the negative impacts of dolphinfish on seabird foraging behaviour.

Marine predators often aggregate at the air-sea boundary layer to pursue shared prey. In such scenarios, seabirds are likely to benefit from underwater predators herding fish schools into tight clusters thereby enhancing seabirds' prey detectability and capture potential. However, this coexistence can lead to competition, affecting not only immediate foraging strategies but also their distribution and interspecies dynamics. We investigated both the longitudinal relationships and instantaneous interactions between streaked shearwaters (Calonectris leucomelas) and common dolphinfish (Coryphaena hippurus), both preying on Japanese anchovy (Engraulis japonicus). Using GPS data from 2011 to 2021, we calculated behavioural parameters for streaked shearwaters as an index of time spent and distance travelled. Despite the abundance of Japanese anchovies, we found that streaked shearwaters might increase their foraging time in the presence of underwater predators. Moreover, video loggers provided direct evidence of streaked shearwaters and common dolphinfish attacking the same fish schools, potentially interfering with bird foraging by dolphinfish. Our results suggest that the presence of underwater predators in a given patch might increase the time spent by seabirds foraging without affecting the distance travelled. This highlights the need for future studies that consider the potential adverse effects of other top predators on seabird prey availability.

Validity of Mobility-Based Exposure Assessment of Air Pollution: A Comparative Analysis with Home-Based Exposure Assessment.

Air pollution exposure is typically assessed at the front door where people live in large-scale epidemiological studies, overlooking individuals' daily mobility out-of-home. However, there is limited evidence that incorporating mobility data into personal air pollution assessment improves exposure assessment compared to home-based assessments. This study aimed to compare the agreement between mobility-based and home-based assessments with personal exposure measurements. We measured repeatedly particulate matter (PM2.5) and black carbon (BC) using a sample of 41 older adults in the Netherlands. In total, 104 valid 24 h average personal measurements were collected. Home-based exposures were estimated by combining participants' home locations and temporal-adjusted air pollution maps. Mobility-based estimates of air pollution were computed based on smartphone-based tracking data, temporal-adjusted air pollution maps, indoor-outdoor penetration, and travel mode adjustment. Intraclass correlation coefficients (ICC) revealed that mobility-based estimates significantly improved agreement with personal measurements compared to home-based assessments. For PM2.5, agreement increased by 64% (ICC: 0.39-0.64), and for BC, it increased by 21% (ICC: 0.43-0.52). Our findings suggest that adjusting for indoor-outdoor pollutant ratios in mobility-based assessments can provide more valid estimates of air pollution than the commonly used home-based assessments, with no added value observed from travel mode adjustments.

Smartphone GPS-Based Exposure to Greenspace and Walkability and Accelerometer-Assessed Physical Activity During Pregnancy and Early Postpartum-Evidence from the MADRES Cohort.

A growing number of studies have associated walkability and greenspace exposure with greater physical activity (PA) in women during pregnancy. However, most studies have focused on examining women's residential environments and neglected exposure in locations outside the home neighborhood. Using 350 person-days (N = 55 participants) of smartphone global positioning system (GPS) location and accelerometer data collected during the first and third trimesters and 4-6 months postpartum from 55 Hispanic pregnant women from the Maternal and Developmental Risks from Environmental and Social Stressors (MADRES) study, we examined the day-level effect of women's exposure to walkability and greenspace on their PA outcomes during pregnancy and in the early postpartum period. Moderate-to-vigorous physical activity [MVPA] minutes per day was assessed using accelerometers. Walkability and greenspace were measured using geographic information systems (GIS) within women's daily activity spaces (i.e., places visited and routes taken) recorded using a smartphone GPS and weighted by time spent. We used a generalized linear mixed-effects model to estimate the effects of daily GPS-derived environmental exposures on day-level MVPA minutes. Results showed that women engaged in 23% more MVPA minutes on days when they had some versus no exposure to parks and open spaces in activity spaces (b = 1.23; 95%CI: 1.02-1.48). In addition, protective effects of daily greenspace and walkability exposure on MVPA were stronger in the first and third trimesters, among first-time mothers, and among women who had high pre-pregnancy body mass index (BMI) and lived in least-safe neighborhoods. Our results suggest that daily greenspace and walkability exposure are important for women's PA and associated health outcomes during pregnancy and early postpartum.

Investigating young children's physical activity through time and place.

BACKGROUND: Previous research indicates the start of primary school (4-5-year-old) as an essential period for the development of children's physical activity (PA) patterns, as from this point, the age-related decline of PA is most often observed. During this period, young children are exposed to a wider variety of environmental- and social contexts and therefore their PA is influenced by more diverse factors. However, in order to understand children's daily PA patterns and identify relevant opportunities for PA promotion, it is important to further unravel in which (social) contexts throughout the day, PA of young children takes place. METHODS: We included a cross-national sample of 21 primary schools from the Startvaardig study. In total, 248 children provided valid accelerometer and global positioning (GPS) data. Geospatial analyses were conducted to quantify PA in (social) environments based on their school and home. Transport-related PA was evaluated using GPS speed-algorithms. PA was analysed at different environments, time-periods and for week- and weekend days separately. RESULTS: Children accumulated an average of 60 min of moderate-to-vigorous PA (MVPA), both during week- and weekend days. Schools contributed to approximately half of daily MVPA during weekdays. During weekends, environments within 100 m from home were important, as well as locations outside the home-school neighbourhood. Pedestrian trips contributed to almost half of the daily MVPA. CONCLUSIONS: We identified several social contexts relevant for children's daily MVPA. Schools have the potential to significantly contribute to young children's PA patterns and are therefore encouraged to systematically evaluate and implement parts of the school-system that stimulate PA and potentially also learning processes. Pedestrian trips also have substantial contribution to daily MVPA of young children, which highlights the importance of daily active transport in school- and parental routines.