Cause and Consequence of Tethering a SubTAD to Different Nuclear Compartments.

Detailed genomic contact maps have revealed that chromosomes are structurally organized in megabase-sized topologically associated domains (TADs) that encompass smaller subTADs. These domains segregate in the nuclear space to form active and inactive nuclear compartments, but cause and consequence of compartmentalization are largely unknown. Here, we combined lacO/lacR binding platforms with allele-specific 4C technologies to track their precise position in the three-dimensional genome upon recruitment of NANOG, SUV39H1, or EZH2. We observed locked genomic loci resistant to spatial repositioning and unlocked loci that could be repositioned to different nuclear subcompartments with distinct chromatin signatures. Focal protein recruitment caused the entire subTAD, but not surrounding regions, to engage in new genomic contacts. Compartment switching was found uncoupled from transcription changes, and the enzymatic modification of histones per se was insufficient for repositioning. Collectively, this suggests that trans-associated factors influence three-dimensional compartmentalization independent of their cis effect on local chromatin composition and activity.

How Do Runners Experience Personalization of Their Training Scheme: The Inspirun E-Coach?

Among runners, there is a high drop-out rate due to injuries and loss of motivation. These runners often lack personalized guidance and support. While there is much potential for sports apps to act as (e-)coaches to help these runners to avoid injuries, set goals, and maintain good intentions, most available running apps primarily focus on persuasive design features like monitoring, they offer few or no features that support personalized guidance (e.g., personalized training schemes). Therefore, we give a detailed description of the working mechanism of Inspirun e-Coach app and on how this app uses a personalized coaching approach with automatic adaptation of training schemes based on biofeedback and GPS-data. We also share insights into how end-users experience this working mechanism. The primary conclusion of this study is that the working mechanism (if provided with accurate data) automatically adapts training sessions to the runners' physical workload and stimulates runners' goal perception, motivation, and experienced personalization. With this mechanism, we attempted to make optimal use of the potential of wearable technology to support the large group of novice or less experienced runners and that by providing insight in our working mechanisms, it can be applied in other technologies, wearables, and types of sports.

Attractive running environments for all? A cross-sectional study on physical environmental characteristics and runners' motives and attitudes, in relation to the experience of the running environment.

BACKGROUND: Running has become one of the most popular sports and has proven benefits for public health. Policy makers are increasingly aware that attractively designed public spaces may promote running. However, little is known about what makes a running environment attractive and restorative for runners and to what extent this depends on characteristics of the runner. This study aims to investigate 1) to what extent intrapersonal characteristics (i.e. motives and attitudes) and perceived environmental characteristics (e.g. quality of the running surface, greenness of the route, feelings of safety and hinderance by other road users) are associated with the perceived attractiveness and restorative capacity of the running environment and 2) to what extent the number of years of running experience modify these associations. METHODS: Cross-sectional data were collected through the online Eindhoven Running Survey 2015 (ERS15) among half marathon runners (N = 2477; response rate 26.6%). Linear regression analyses were performed for two outcomes separately (i.e. perceived attractiveness and perceived restorative capacity of the running environment) to investigate their relations with motives and attitudes, perceived environmental characteristics and interactions between perceived environmental characteristics and number of years of running experience. RESULTS: Perceived environmental characteristics, including green and lively routes and a comfortable running surface were more important for runners' evaluation of the attractiveness and restorative capacity of the running environment than runners' motives and attitudes. In contrast to experienced runners, perceived hinder from unleashed dogs and pedestrians positively impacted the attractiveness and restorative capacity for less experienced runners. CONCLUSIONS: Perceived environmental characteristics were important determinants of the attractiveness and restorative capacity of the running environment for both novice and experienced runners. However, green and lively elements in the running environment and hinderances by cars were more important for less experienced runners. In order to keep novice runners involved in running it is recommended to design comfortable running tracks and routes and provide good access to attractive, green and lively spaces.

Characterization and dynamics of pericentromere-associated domains in mice.

Despite recent progress in genome topology knowledge, the role of repeats, which make up the majority of mammalian genomes, remains elusive. Satellite repeats are highly abundant sequences that cluster around centromeres, attract pericentromeric heterochromatin, and aggregate into nuclear chromocenters. These nuclear landmark structures are assumed to form a repressive compartment in the nucleus to which genes are recruited for silencing. We have designed a strategy for genome-wide identification of pericentromere-associated domains (PADs) in different mouse cell types. The ∼1000 PADs and non-PADs have similar chromatin states in embryonic stem cells, but during lineage commitment, chromocenters progressively associate with constitutively inactive genomic regions at the nuclear periphery. This suggests that PADs are not actively recruited to chromocenters, but that chromocenters are themselves attracted to inactive chromatin compartments. However, we also found that experimentally induced proximity of an active locus to chromocenters was sufficient to cause gene repression. Collectively, our data suggest that rather than driving nuclear organization, pericentromeric satellite repeats mostly co-segregate with inactive genomic regions into nuclear compartments where they can contribute to stable maintenance of the repressed status of proximal chromosomal regions.

Emissions and air quality impacts of truck-to-rail freight modal shifts in the Midwestern United States.

We present an examination of the potential emissions and air quality benefits of shifting freight from truck to rail in the upper Midwestern United States. Using a novel, freight-specific emissions inventory (the Wisconsin Inventory of Freight Emissions, WIFE) and a three-dimensional Eulerian photochemical transport model (the Community Multiscale Air Quality Model, CMAQ), we quantify how specific freight mode choices impact ambient air pollution concentrations. Using WIFE, we developed two modal shift scenarios: one focusing on intraregional freight movements within the Midwest and a second on through-freight movements through the region. Freight truck and rail emissions inventories for each scenario were gridded to a 12 km × 12 km horizontal resolution as input to CMAQ, along with emissions from all other major sectors, and three-dimensional time-varying meteorology from the Weather Research and Forecasting model (WRF). The through-freight scenario reduced monthly mean (January and July) localized concentrations of nitrogen dioxide (NO2) by 28% (-2.33 ppbV) in highway grid cells, and reduced elemental carbon (EC) by 16% (-0.05 µg/m(3)) in highway grid cells. There were corresponding localized increases in railway grid cells of 25% (+0.83 ppbV) for NO2, and 22% (+0.05 µg/m(3)) for EC. The through-freight scenario reduced CO2 emissions 31% compared to baseline trucking. The through-freight scenario yields a July mean change in ground-level ambient PM2.5 and O3 over the central and eastern part of the domain (up to -3%).

Two of a Kind? Similarities and Differences between Runners and Walkers in Sociodemographic Characteristics, Sports Related Characteristics and Wearable Usage.

As the two prime examples of sport light, running and walking have become very popular sports activities in the past decades. There are references in the literature of similarities between both sports, however these parallels have never been studied. In addition, the current digitalisation of society can have important influences on the further diversification of profiles. Data of a large-scale population survey among runners and walkers (n = 4913) in Flanders (Belgium) were used to study their sociodemographic, sports related and attitudinal characteristics, and wearable usage. The results showed that walkers are more often female, older, lower educated, and less often use wearables. To predict wearable usage, sports-related and attitudinal characteristics are important among runners but not among walkers. Motivational variables to use wearables are important to predict wearable usage among both runners and walkers. Additionally, whether or not the runner or walker registers the heart rate is the most important predictor. The present study highlights similarities and differences between runners and walkers. By adding attitudinal characteristics and including walkers this article provides new insights to the literature, which can be used by policymakers and professionals in the field of sport, exercise and health, and technology developers to shape their services accordingly.

Characterization of ground-based atmospheric pollution and meteorology sampling stations during the Lake Michigan Ozone Study 2017.

The Lake Michigan Ozone Study 2017 (LMOS 2017) in May and June 2017 enabled study of transport, emissions, and chemical evolution related to ozone air pollution in the Lake Michigan airshed. Two highly instrumented ground sampling sites were part of a wider sampling strategy of aircraft, shipborne, and ground-based mobile sampling. The Zion, Illinois site (on the coast of Lake Michigan, 67 km north of Chicago) was selected to sample higher NOx air parcels having undergone less photochemical processing. The Sheboygan, Wisconsin site (on the coast of Lake Michigan, 211 km north of Chicago) was selected due to its favorable location for the observation of photochemically aged plumes during ozone episodes involving southerly winds with lake breeze. The study encountered elevated ozone during three multiday periods. Daytime ozone episode concentrations at Zion were 60 ppb for ozone, 3.8 ppb for NOx, 1.2 ppb for nitric acid, and 8.2 µg m-3 for fine particulate matter. At Sheboygan daytime, ozone episode concentrations were 60 ppb for ozone, 2.6 ppb for NOx, and 3.0 ppb for NOy. To facilitate informed use of the LMOS 2017 data repository, we here present comprehensive site description, including airmass influences during high ozone periods of the campaign, overview of meteorological and pollutant measurements, analysis of continuous emission monitor data from nearby large point sources, and characterization of local source impacts from vehicle traffic, large point sources, and rail. Consistent with previous field campaigns and the conceptual model of ozone episodes in the area, trajectories from the southwest, south, and lake breeze trajectories (south or southeast) were overrepresented during pollution episodes. Local source impacts from vehicle traffic, large point sources, and rail were assessed and found to represent less than about 15% of typical concentrations measured. Implications for model-observation comparison and design of future field campaigns are discussed.Implications: The Lake Michigan Ozone Study 2017 (LMOS 2017) was conducted along the western shore of Lake Michigan, and involved two well-instrumented coastal ground sites (Zion, IL, and Sheboygan, WI). LMOS 2017 data are publicly available, and this paper provides detailed site characterization and measurement summary to enable informed use of repository data. Minor local source impacts were detected but were largely confined to nighttime conditions of less interest for ozone episode analysis and modeling. The role of these sites in the wider field campaign and their detailed description facilitates future campaign planning, informed data repository use, and model-observation comparison.

Runner's Perceptions of Reasons to Quit Running: Influence of Gender, Age and Running-Related Characteristics.

Physical inactivity has become a major public health concern and, consequently, the awareness of striving for a healthy lifestyle has increased. As a result, the popularity of recreational sports, such as running, has increased. Running is known for its low threshold to start and its attractiveness for a heterogeneous group of people. Yet, one can still observe high drop-out rates among (novice) runners. To understand the reasons for drop-out as perceived by runners, we investigate potential reasons to quit running among short distance runners (5 km and 10 km) (n = 898). Data used in this study were drawn from the standardized online Eindhoven Running Survey 2016 (ERS16). Binary logistic regressions were used to investigate the relation between reasons to quit running and different variables like socio-demographic variables, running habits and attitudes, interests, and opinions (AIOs) on running. Our results indicate that, not only people of different gender and age show significant differences in perceived reasons to quit running, also running habits, (e.g., running context and frequency) and AIOs are related to perceived reasons to quit running too. With insights into these related variables, potential drop-out reasons could help health professionals in understanding and lowering drop-out rates among recreational runners.

Understanding Different Types of Recreational Runners and How They Use Running-Related Technology.

This study aims to help professionals in the field of running and running-related technology (i.e., sports watches and smartphone applications) to address the needs of runners. It investigates the various runner types-in terms of their attitudes, interests, and opinions (AIOs) with regard to running-and studies how they differ in the technology they use. Data used in this study were drawn from the standardized online Eindhoven Running Survey 2016 (ERS2016). In total, 3723 participants completed the questionnaire. Principal component analysis and cluster analysis were used to identify the different running types, and crosstabs obtained insights into the use of technology between different typologies. Based on the AIOs, four distinct runner types were identified: casual individual, social competitive, individual competitive, and devoted runners. Subsequently, we related the types to their use of sports watches and apps. Our results show a difference in the kinds of technology used by different runner types. Differentiation between types of runners can be useful for health professionals, policymakers involved in public health, engineers, and trainers or coaches to adapt their services to specific segments, in order to make use of the full potential of running-related systems to support runners to stay active and injury-free and contribute to a healthy lifestyle.

Analysis of the Features Important for the Effectiveness of Physical Activity-Related Apps for Recreational Sports: Expert Panel Approach.

BACKGROUND: A large number of people participate in individual or unorganized sports on a recreational level. Furthermore, many participants drop out because of injury or lowered motivation. Potentially, physical activity-related apps could motivate people during sport participation and help them to follow and maintain a healthy active lifestyle. It remains unclear what the quality of running, cycling, and walking apps is and how it can be assessed. Quality of these apps was defined as having a positive influence on participation in recreational sports. This information will show which features need to be assessed when rating physical activity-related app quality. OBJECTIVE: The aim of this study was to identify expert perception on which features are important for the effectiveness of physical activity-related apps for participation in individual, recreational sports. METHODS: Data were gathered via an expert panel approach using the nominal group technique. Two expert panels were organized to identify and rank app features relevant for sport participation. Experts were researchers or professionals in the field of industrial design and information technology (technology expert panel) and in the field of behavior change, health, and human movement sciences who had affinity with physical activity-related apps (health science expert panel). Of the 24 experts who were approached, 11 (46%) agreed to participate. Each panel session consisted of three consultation rounds. The 10 most important features per expert were collected. We calculated the frequency of the top 10 features and the mean importance score per feature (0-100). The sessions were taped and transcribed verbatim; a thematic analysis was conducted on the qualitative data. RESULTS: In the technology expert panel, applied feedback and feedforward (91.3) and fun (91.3) were found most important (scale 0-100). Together with flexibility and look and feel, these features were mentioned most often (all n=4 [number of experts]; importance scores=41.3 and 43.8, respectively). The experts in the health science expert panels a and b found instructional feedback (95.0), motivating or challenging (95.0), peer rating and use (92.0), motivating feedback (91.3), and monitoring or statistics (91.0) most important. Most often ranked features were monitoring or statistics, motivating feedback, works good technically, tailoring starting point, fun, usability anticipating or context awareness, and privacy (all n=3-4 [number of experts]; importance scores=16.7-95.0). The qualitative analysis resulted in four overarching themes: (1) combination behavior change, technical, and design features needed; (2) extended feedback and tailoring is advised; (3) theoretical or evidence base as standard; and (4) entry requirements related to app use. CONCLUSIONS: The results show that a variety of features, including design, technical, and behavior change, are considered important for the effectiveness of physical activity-related apps by experts from different fields of expertise. These insights may assist in the development of an improved app rating scale.

Who uses running apps and sports watches? Determinants and consumer profiles of event runners' usage of running-related smartphone applications and sports watches.

Individual and unorganized sports with a health-related focus, such as recreational running, have grown extensively in the last decade. Consistent with this development, there has been an exponential increase in the availability and use of electronic monitoring devices such as smartphone applications (apps) and sports watches. These electronic devices could provide support and monitoring for unorganized runners, who have no access to professional trainers and coaches. The purpose of this paper is to gain insight into the characteristics of event runners who use running-related apps and sports watches. This knowledge is useful from research, design, and marketing perspectives to adequately address unorganized runners' needs, and to support them in healthy and sustainable running through personalized technology. Data used in this study are drawn from the standardized online Eindhoven Running Survey 2014 (ERS14). In total, 2,172 participants in the Half Marathon Eindhoven 2014 completed the questionnaire (a response rate of 40.0%). Binary logistic regressions were used to analyze the impact of socio-demographic variables, running-related variables, and psychographic characteristics on the use of running-related apps and sports watches. Next, consumer profiles were identified. The results indicate that the use of monitoring devices is affected by socio-demographics as well as sports-related and psychographic variables, and this relationship depends on the type of monitoring device. Therefore, distinctive consumer profiles have been developed to provide a tool for designers and manufacturers of electronic running-related devices to better target (unorganized) runners' needs through personalized and differentiated approaches. Apps are more likely to be used by younger, less experienced and involved runners. Hence, apps have the potential to target this group of novice, less trained, and unorganized runners. In contrast, sports watches are more likely to be used by a different group of runners, older and more experienced runners with higher involvement. Although apps and sports watches may potentially promote and stimulate sports participation, these electronic devices do require a more differentiated approach to target specific needs of runners. Considerable efforts in terms of personalization and tailoring have to be made to develop the full potential of these electronic devices as drivers for healthy and sustainable sports participation.

Identification of Chloride Intracellular Channel Protein 3 as a Novel Gene Affecting Human Bone Formation.

Osteoporosis is a common skeletal disorder characterized by low bone mass leading to increased bone fragility and fracture susceptibility. The bone building cells, osteoblasts, are derived from mesenchymal stromal cells (MSCs); however, with increasing age osteogenic differentiation is diminished and more adipocytes are seen in the bone marrow, suggesting a shift in MSC lineage commitment. Identification of specific factors that stimulate osteoblast differentiation from human MSCs may deliver therapeutic targets to treat osteoporosis. The aim of this study was to identify novel genes involved in osteoblast differentiation of human bone marrow-derived MSCs (hMSCs). We identified the gene chloride intracellular channel protein 3 (CLIC3) to be strongly upregulated during MSC-derived osteoblast differentiation. Lentiviral overexpression of CLIC3 in hMSCs caused a 60% increase of matrix mineralization. Conversely, knockdown of CLIC3 in hMSCs using two short-hairpin RNAs (shRNAs) against CLIC3 resulted in a 69% to 76% reduction in CLIC3 mRNA expression, 53% to 37% less alkaline phosphatase (ALP) activity, and 78% to 88% less matrix mineralization compared to scrambled control. Next, we used an in vivo human bone formation model in which hMSCs lentivirally transduced with the CLIC3 overexpression construct were loaded onto a scaffold (hydroxyapatite-tricalcium-phosphate), implanted under the skin of NOD-SCID mice, and analyzed for bone formation 8 weeks later. CLIC3 overexpression led to a 15-fold increase in bone formation (0.33% versus 5.05% bone area relative to scaffold). Using a Clic3-His-tagged pull-down assay and liquid chromatography-mass spectrometry (LS/MS)-based proteomics analysis in lysates of osteogenically differentiated hMSCs, we showed that CLIC3 interacts with NIMA-related kinase 9 (NEK9) and phosphatidylserine synthase 1 (PTDSS1) in vitro, and this finding was supported by immunofluorescent analysis. In addition, inhibition of NEK9 or PTDSS1 gene expression by shRNAs inhibited osteoblast differentiation and mineralization. In conclusion, we successfully identified CLIC3 to be a lineage-specific gene regulating osteoblast differentiation and bone formation through its interaction with NEK9 and PTDSS1. © The Authors. JBMR Plus is published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.

Efficacy of a regional network for ovarian cancer care.

OBJECTIVE: To study the influence of a regional collaboration in epithelial ovarian cancer care on staging procedures, debulking results, and survival. METHODS: In an effort to optimize epithelial ovarian cancer treatment, a regional collaboration was introduced in the Netherlands in 2000. Gynecologic oncologists from the university center conducted surgery in community hospitals when ovarian cancer was considered based on the risk of malignancy index or clinical suspicion. The National Cancer Registry registered 1,554 patients with epithelial ovarian cancer diagnosed in 11 participating Dutch hospitals between 1996 and 2010. Surgical procedures were compared during three periods (1996-1999, 2000-2004, and 2005-2009). Log-rank tests compared Kaplan-Meier survival curves of progression-free and overall survival before (1996-2000) and during the start of the collaboration (2001-2005). RESULTS: Staging was adequate for 139 patients (23.0%) before collaboration, and this proportion increased during the study periods to 32.1% and 62.1% (P<.01), when gynecologic oncologists more often staged cancer in patients (36.7% compared with 54.7% and 80.6%; P<.01). For 1,197 patients with advanced stage disease (stage IIb or greater), the proportion of debulking procedures with an optimal (residual volume less than1 cm) as well as a complete result (no residuals) increased during the 14-year study period from 57.4% to 76.5% (P<.01) and from 24.1% to 43.4% (P<.01), respectively. Survival rates were similar before and during the start of the collaboration. In multivariable analysis, the treatment variables completeness of debulking, chemotherapy, and gynecologic oncologist attendance were independent prognostic factors for overall survival, as were age, stage, and tumor grade. CONCLUSIONS: After regional collaboration, gynecologic oncologists attended more surgeries and surgical outcomes improved, but progress in survival could not be demonstrated. Regional collaboration improved care for ovarian cancer patients. LEVEL OF EVIDENCE: II.

Increased plasma corticosterone levels after periaqueductal gray stimulation-induced escape reaction or panic attacks in rats.

The hypothalamo-pituitary-adrenal (HPA) axis is involved in stress, depression and anxiety. Controversy exists on HPA axis activation during panic attacks (PAs). We examined whether the HPA axis is involved in the escape or panic-like response in an animal model of PAs induced by electrical stimulation of the dorsolateral periaqueductal gray (dlPAG) in rats. Additionally, rats were also treated with chronic administration of buspirone (BUSP) and escitalopram (ESCIT), respectively; and they were stimulated in the open-field arena for panic-like reaction. Levels of stress hormone corticosterone were measured following 30 min after escape or panic condition. Our results demonstrated that the levels of plasma corticosterone were significantly increased after the induction of escape or panic-like response in comparison with the sham animals. The levels of corticosterone were significantly decreased in the dlPAG stimulated groups after rats were treated chronically with the ESCIT but not the BUSP as compared to the saline treated animals. Importantly, the increase of corticosterone level after escape or panic-like response was paralleled by an increase of neuronal activation of c-Fos in both the parvocellular and magnocellular paraventricular nucleus of the hypothalamus. Moreover, the c-Fos data also showed a decrease in the number of positive cells particularly for the ESCIT as well as the BUSP in comparison with the saline stimulated animals. In conclusion, the present study clearly demonstrated that PA or escape response activates the HPA axis and it remains difficult to anticipate the mechanism underlying HPA axis during PAs and its relationship with 5-HT drugs.