Plant immunity protects plants from numerous potentially pathogenic microbes. The biological network that controls plant inducible immunity must function effectively even when network components are ...targeted and disabled by pathogen effectors. Network buffering could confer this resilience by allowing different parts of the network to compensate for loss of one another's functions. Networks rich in buffering rely on interactions within the network, but these mechanisms are difficult to study by simple genetic means. Through a network reconstitution strategy, in which we disassemble and stepwise reassemble the plant immune network that mediates Pattern-Triggered-Immunity, we have resolved systems-level regulatory mechanisms underlying the Arabidopsis transcriptome response to the immune stimulant flagellin-22 (flg22). These mechanisms show widespread evidence of interactions among major sub-networks-we call these sectors-in the flg22-responsive transcriptome. Many of these interactions result in network buffering. Resolved regulatory mechanisms show unexpected patterns for how the jasmonate (JA), ethylene (ET), phytoalexin-deficient 4 (PAD4), and salicylate (SA) signaling sectors control the transcriptional response to flg22. We demonstrate that many of the regulatory mechanisms we resolved are not detectable by the traditional genetic approach of single-gene null-mutant analysis. Similar to potential pathogenic perturbations, null-mutant effects on immune signaling can be buffered by the network.
Autism Spectrum Disorder affects up to 2.5% of children and is associated with harmful health outcomes (e.g. obesity). Low levels of physical activity and high levels of sedentary behaviors may ...contribute to harmful health outcomes. To systematically review the prevalence and correlates of physical activity and sedentary behaviors in children with Autism Spectrum Disorder, electronic databases (PsycINFO, SPORTDiscus, EMBASE, Medline) were searched from inception to November 2015. The review was registered with PROSPERO (CRD42014013849). Peer-reviewed, English language studies were included. Two reviewers screened potentially relevant articles. Outcomes of interest were physical activity and sedentary behaviour levels and their potential correlates. Data were collected and analysed in 2015. Of 35 included studies, 15 reported physical activity prevalence, 10 reported physical activity correlates, 18 reported sedentary behavior prevalence, and 10 reported sedentary behavior correlates. Estimates of children's physical activity (34-166 mins/day, average 86 mins/day) and sedentary behavior (126-558 mins/day in screen time, average 271 mins/day; 428-750 mins/day in total sedentary behavior, average 479 mins/day) varied across studies. Age was consistently inversely associated, and sex inconsistently associated with physical activity. Age and sex were inconsistently associated with sedentary behavior. Sample sizes were small. All but one of the studies were classified as having high risk of bias. Few correlates have been reported in sufficient studies to provide overall estimates of associations. Potential correlates in the physical environment remain largely unexamined. This review highlights varying levels of physical activity and sedentary behavior in children with Autism Spectrum Disorder. Research is needed to consistently identify the correlates of these behaviors. There is a critical need for interventions to support healthy levels of these behaviors. Author abstract
To date, no reviews have investigated the evidence of tracking of physical activity and sedentary behavior specifically during early childhood (aged 0-5.9 years) or from early childhood to middle ...childhood (aged 6-12 years). It is important to review the evidence of tracking of these behaviors to determine their stability during the foundational early years of life.
A literature search of studies was conducted in seven electronic databases (January 1980 to April 2012). Studies were compared on methodologic quality and evidence of tracking of physical activity or sedentary behavior. Tracking was defined as the stability (or relative ranking within a cohort) of behaviors, such as physical activity and sedentary behavior, over time.
Eleven studies met the inclusion criteria. All studies reporting physical activity outcomes had high methodologic quality; 71% of studies reporting sedentary behavior outcomes had high methodologic quality. Of the tracking coefficients for physical activity, 4% were large, 60% were moderate, and 36% were small. Of the tracking coefficients for sedentary behavior, 33% were large, 50% were moderate, and 17% were small. Overall, there was evidence of moderate tracking of physical activity during early childhood, and from early childhood to middle childhood, and of moderate-to-large tracking of sedentary behavior during early childhood and from early childhood to middle childhood.
This review highlights the importance of establishing recommended levels of physical activity and sedentary behavior during the early years of life. Based on this review, the following recommendations are made: (1) early childhood should be targeted as a critical time to promote healthy lifestyle behaviors through methodologically sound prevention studies; and (2) future tracking studies should assess a broad range of sedentary behaviors using objective measures.
Evaluate the predictive validity of ActiGraph energy expenditure equations and the classification accuracy of physical activity intensity cut-points in preschoolers.
Forty children aged 4-6 years ...(5.3±1.0 years) completed a ∼150-min room calorimeter protocol involving age-appropriate sedentary, light and moderate-to vigorous-intensity physical activities. Children wore an ActiGraph GT3X on the right mid-axillary line of the hip. Energy expenditure measured by room calorimetry and physical activity intensity classified using direct observation were the criterion methods. Energy expenditure was predicted using Pate and Puyau equations. Physical activity intensity was classified using Evenson, Sirard, Van Cauwenberghe, Pate, Puyau, and Reilly, ActiGraph cut-points.
The Pate equation significantly overestimated VO2 during sedentary behaviors, light physical activities and total VO2 (P<0.001). No difference was found between measured and predicted VO2 during moderate-to vigorous-intensity physical activities (P = 0.072). The Puyau equation significantly underestimated activity energy expenditure during moderate-to vigorous-intensity physical activities, light-intensity physical activities and total activity energy expenditure (P<0.0125). However, no overestimation of activity energy expenditure during sedentary behavior was found. The Evenson cut-point demonstrated significantly higher accuracy for classifying sedentary behaviors and light-intensity physical activities than others. Classification accuracy for moderate-to vigorous-intensity physical activities was significantly higher for Pate than others.
Available ActiGraph equations do not provide accurate estimates of energy expenditure across physical activity intensities in preschoolers. Cut-points of ≤25 counts⋅15 s(-1) and ≥420 counts⋅15 s(-1) for classifying sedentary behaviors and moderate-to vigorous-intensity physical activities, respectively, are recommended.
The skin confers biophysical and immunological protection through a complex cellular network established early in embryonic development. We profiled the transcriptomes of more than 500,000 single ...cells from developing human fetal skin, healthy adult skin, and adult skin with atopic dermatitis and psoriasis. We leveraged these datasets to compare cell states across development, homeostasis, and disease. Our analysis revealed an enrichment of innate immune cells in skin during the first trimester and clonal expansion of disease-associated lymphocytes in atopic dermatitis and psoriasis. We uncovered and validated in situ a reemergence of prenatal vascular endothelial cell and macrophage cellular programs in atopic dermatitis and psoriasis lesional skin. These data illustrate the dynamism of cutaneous immunity and provide opportunities for targeting pathological developmental programs in inflammatory skin diseases.
Abstract Objective To systematically review the correlates of physical activity and sedentary behavior among children in Early Childhood Education and Care (ECEC) services. Appropriate levels of ...physical activity and sedentary behavior are important to promote in ECEC services. Methods A systematic search of 8 databases identified 27 studies published between 1992 and 2015 that met the inclusion criteria. The data were collected and analyzed in 2014 and 2015, and variables were categorized using a Social Ecological Framework. Results Sixty-six variables were identified. The domains of child characteristics (18 studies) and physical environmental factors (17 studies) were most consistently studied, and, for physical activity had the most positive associations. The strongest associations of physical activity were: child's sex and age, children's gross motor coordination, provision of active opportunities for physical activity, and features of outdoor environments (size, use of and presence). The only strong association for sedentary behavior was the presence of outdoor environments. Conclusion The correlates of physical activity and sedentary behavior in ECEC services vary. It appears that the most significant influence from within these settings is the physical environments for both physical activity and sedentary behavior. There was an absence of consistent evidence at the educator and organizational levels. Further research in this area should focus on effective use of space, intentional teaching opportunities and well as professional development for educators with an emphasis on their role as a facilitator of quality experiences. This review has been registered with Prospero, #CRD42014013660.
Abstract
Motivation
Cell-type-specific surface proteins can be exploited as valuable markers for a range of applications including immunophenotyping live cells, targeted drug delivery and in vivo ...imaging. Despite their utility and relevance, the unique combination of molecules present at the cell surface are not yet described for most cell types. A significant challenge in analyzing ‘omic’ discovery datasets is the selection of candidate markers that are most applicable for downstream applications.
Results
Here, we developed GenieScore, a prioritization metric that integrates a consensus-based prediction of cell surface localization with user-input data to rank-order candidate cell-type-specific surface markers. In this report, we demonstrate the utility of GenieScore for analyzing human and rodent data from proteomic and transcriptomic experiments in the areas of cancer, stem cell and islet biology. We also demonstrate that permutations of GenieScore, termed IsoGenieScore and OmniGenieScore, can efficiently prioritize co-expressed and intracellular cell-type-specific markers, respectively.
Availability and implementation
Calculation of GenieScores and lookup of SPC scores is made freely accessible via the SurfaceGenie web application: www.cellsurfer.net/surfacegenie.
Contact
Rebekah.gundry@unmc.edu
Supplementary information
Supplementary data are available at Bioinformatics online.
In 2017, the Australian Government funded the update of the National Physical Activity Recommendations for Children 0-5 years, with the intention that they be an integration of movement behaviours ...across the 24-h period. The benefit for Australia was that it could leverage research in Canada in the development of their 24-h guidelines for the early years. Concurrently, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group published a model to produce guidelines based on adoption, adaption and/or de novo development using the GRADE evidence-to-decision framework. Referred to as the GRADE-ADOLOPMENT approach, it allows guideline developers to follow a structured and transparent process in a more efficient manner, potentially avoiding the need to unnecessarily repeat costly tasks such as conducting systematic reviews. The purpose of this paper is to outline the process and outcomes for adapting the Canadian 24-Hour Movement Guidelines for the Early Years to develop the Australian 24-Hour Movement Guidelines for the Early Years guided by the GRADE-ADOLOPMENT framework.
The development process was guided by the GRADE-ADOLOPMENT approach. A Leadership Group and Consensus Panel were formed and existing credible guidelines identified. The draft Canadian 24-h integrated movement guidelines for the early years best met the criteria established by the Panel. These were evaluated based on the evidence in the GRADE tables, summaries of findings tables and draft recommendations from the Canadian Draft Guidelines. Updates to each of the Canadian systematic reviews were conducted and the Consensus Panel reviewed the evidence for each behaviour separately and made a decision to adopt or adapt the Canadian recommendations for each behaviour or create de novo recommendations. An online survey was then conducted (n = 302) along with five focus groups (n = 30) and five key informant interviews (n = 5) to obtain feedback from stakeholders on the draft guidelines.
Based on the evidence from the Canadian systematic reviews and the updated systematic reviews in Australia, the Consensus Panel agreed to adopt the Canadian recommendations and, apart from some minor changes to the wording of good practice statements, keep the wording of the guidelines, preamble and title of the Canadian Guidelines. The Australian Guidelines provide evidence-informed recommendations for a healthy day (24-h), integrating physical activity, sedentary behaviour (including limits to screen time), and sleep for infants (<1 year), toddlers (1-2 years) and preschoolers (3-5 years).
To our knowledge, this is only the second time the GRADE-ADOLOPMENT approach has been used. Following this approach, the judgments of the Australian Consensus Panel did not differ sufficiently to change the directions and strength of the recommendations and as such, the Canadian recommendations were adopted with very minor alterations. This allowed the Guidelines to be developed much faster and at lower cost. As such, we would recommend the GRADE-ADOLOPMENT approach, especially if a credible set of guidelines, with all supporting materials and developed using a transparent process, is available. Other countries may consider using this approach when developing and/or revising national movement guidelines.
Peptide cleanup is essential for the removal of contaminating substances that may be introduced during sample preparation steps in bottom-up proteomic workflows. Recent studies have described ...benefits of carboxylate-modified paramagnetic particles over traditional reversed-phase methods for detergent and polymer removal, but challenges with reproducibility have limited the widespread implementation of this approach among laboratories. To overcome these challenges, the current study systematically evaluated key experimental parameters regarding the use of carboxylate-modified paramagnetic particles and determined those that are critical for maximum performance and peptide recovery and those for which the protocol is tolerant to deviation. These results supported the development of a detailed, easy-to-use standard operating protocol, termed SP2, which can be applied to remove detergents and polymers from peptide samples while concentrating the sample in solvent that is directly compatible with typical LC–MS workflows. We demonstrate that SP2 can be applied to phosphopeptides and glycopeptides and that the approach is compatible with robotic liquid handling for automated sample processing. Altogether, the results of this study and accompanying detailed operating protocols for both manual and automated processing are expected to facilitate reproducible implementation of SP2 for various proteomics applications and will especially benefit core or shared resource facilities where unknown or unexpected contaminants may be particularly problematic.
produces ascaroside pheromones to control its development and behavior. Even minor structural differences in the ascarosides have dramatic consequences for their biological activities. Here, we ...identify a mechanism that enables
to dynamically tailor the fatty-acid side chains of the indole-3-carbonyl (IC)-modified ascarosides it has produced. In response to starvation,
uses the peroxisomal acyl-CoA synthetase ACS-7 to activate the side chains of medium-chain IC-ascarosides for β-oxidation involving the acyl-CoA oxidases ACOX-1.1 and ACOX-3. This pathway rapidly converts a favorable ascaroside pheromone that induces aggregation to an unfavorable one that induces the stress-resistant dauer larval stage. Thus, the pathway allows the worm to respond to changing environmental conditions and alter its chemical message without having to synthesize new ascarosides de novo. We establish a new model for biosynthesis of the IC-ascarosides in which side-chain β-oxidation is critical for controlling the type of IC-ascarosides produced.
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