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Abstract Background Eating behaviours have been suggested relating to obesity development. The Children's Eating Behaviour Questionnaire (CEBQ) is a parent-report measure constructed to assess multiple dimensions of eating behavior for children. This study aimed to test the validity of the Chinese version of Children's Eating Behaviour Questionnaire (CEBQ) in Chinese children aged 12-18 months. We examined factor structure and the reliability of the Chinese version of the CEBQ, the associations between children's eating behaviours and children's weight (BMI SDS) were assessed. Methods 219 questionnaires were filled out by the caregivers, approached in community health care centers in two cities in China. BMI of each child was calculated and converted to BMI SDS. Factor validation (Principal Component Analysis, exploratory factor analysis) on all CEBQ items was performed and gender difference in eating behaviours was examined. Correlations between eating behaviours and the child's BMI SDS were analyzed by linear regression analysis controlling for gender, parental combined weight, and education. Results The factor analysis revealed a seven-factor solution, with factor 'food responsiveness' (FR) split into two. 'Satiety responsiveness' (SR) and 'Enjoyment of food' (EF) factors were not detected. Interestingly, boys scored higher than girls in the FR scales, whereas girls had a higher score in 'food fussiness' (FF) scale. Conclusions We conclude that although a valuable psychometric instrument, CEBQ might be affected by age and cultural differences. Therefore, adjusting it in order to fit the Chinese population was suggested. We did not find an association between eating behaviours and children's BMI SDS, when it was controlled for gender and parental weight.

Abstract Background The Children's Eating Behaviour Questionnaire (CEBQ) is a multi-dimensional, parent-reported questionnaire measuring children's eating behaviours related to obesity risk, i.e. 'enjoyment of food', 'food responsiveness', 'slowness in eating' and 'satiety responsiveness'. It has not previously been validated in a Swedish population, neither on children under the age of 2 years. In the present study we examined the factor structure and the reliability of the Swedish version of the CEBQ, for use in an obesity intervention programme targeting preschool children 1-6 years. Further, the associations between eating behaviours and children's age, gender and relative weight (BMI SDS) and parental weight were investigated. Methods Parents to 174 children aged 1-6 years (50% girls, mean age 3.8 years), recruited from five kindergartens in Stockholm, completed the Swedish version of the CEBQ. Data on children's weight and height, parental weight, height and educational level was collected. Children's relative weight was calculated for a subpopulation (mean BMI SDS -0.4, n = 47). Factorial validation (Principal Component Analysis) on all CEBQ items was performed. Differences in eating behaviours by age, gender and parental weight were examined. Correlations between eating behaviours and the child's BMI SDS were analysed controlling for age, gender, parental weight and education in linear regression analyses. Results The factor analysis revealed a seven factor solution with good psychometric properties, similar to the original structure. The behaviour scales 'overeating'/'food responsiveness', 'enjoyment of food' and 'emotional undereating' decreased with age and 'food fussiness' increased with age. Eating behaviours did not differ between girls and boys. The children's relative weight was not related to any of the eating behaviours when controlling for age, gender, parental weight and education, and only associated with parental weight status. Conclusions Our results support the use of the CEBQ as a psychometric instrument for assessing children's eating behaviours in Swedish children aged 1-6 years. Measuring obesity related eating behaviours in longitudinal and interventional studies would offer opportunities for studying causal effects of eating behaviours in the development of obesity in children.

Abstract Background Overweight and obesity have a dramatic negative impact on children's health not only during the childhood but also throughout the adult life. Preventing the development of obesity in children is therefore a world-wide health priority. There is an obvious urge for sustainable and evidenced-based interventions that are suitable for families with young children, especially for families with overweight or obese parents. We have developed a prevention program, Early STOPP, combating multiple obesity-promoting behaviors such unbalanced diet, physical inactivity and disturbed sleeping patterns. We also aim to evaluate the effectiveness of the early childhood obesity prevention in a well-characterized population of overweight or obese parents. This protocol outlines methods for the recruitment phase of the study. Design and methods This randomized controlled trial (RCT) targets overweight and/or obese parents with infants, recruited from the Child Health Care Centers (CHCC) within the Stockholm area. The intervention starts when infants are one year of age and continues until they are six and is regularly delivered by a trained coach (dietitian, physiotherapist or a nurse). The key aspects of Early STOPP family intervention are based on Swedish recommendations for CHCC, which include advices on healthy food choices and eating patterns, increasing physical activity/reducing sedentary behavior and regulating sleeping patterns. Discussion The Early STOPP trial design addresses weaknesses of previous research by recruiting from a well-characterized population, defining a feasible, theory-based intervention and assessing multiple measurements to validate and interpret the program effectiveness. The early years hold promise as a time in which obesity prevention may be most effective. To our knowledge, this longitudinal RCT is the first attempt to demonstrate whether an early, long-term, targeted health promotion program focusing on healthy eating, physical activity/reduced sedentary behaviors and normalizing sleeping patterns could be effective. If proven so, Early STOPP may protect children from the development of overweight and obesity. Trial registration The protocol for this study is registered with the clinical trials registry clinicaltrials.gov, ID: ES-2010)

The gradient expansion is the fundamental organizing principle underlying relativistic hydrodynamics, yet understanding its convergence properties for general nonlinear flows has posed a major challenge. We introduce a simple method to address this question in a class of fluids modeled by Israel-Stewart-type relaxation equations. We apply it to (1+1)-dimensional flows and provide numerical evidence for factorially divergent gradient expansions. This generalizes results previously only obtained for (0+1)-dimensional comoving flows, notably Bjorken flow. We also demonstrate that the only known nontrivial case of a convergent hydrodynamic gradient expansion at the nonlinear level relies on Bjorken flow symmetries and becomes factorially divergent as soon as these are relaxed. Finally, we show that factorial divergence can be removed using a momentum space cutoff, which generalizes a result obtained earlier in the context of linear response.

Single-cell transcriptomics can provide quantitative molecular signatures for large, unbiased samples of the diverse cell types in the brain 1-3 . With the proliferation of multi-omics datasets, a major challenge is to validate and integrate results into a biological understanding of cell-type organization. Here we generated transcriptomes and epigenomes from more than 500,000 individual cells in the mouse primary motor cortex, a structure that has an evolutionarily conserved role in locomotion. We developed computational and statistical methods to integrate multimodal data and quantitatively validate cell-type reproducibility. The resulting reference atlas-containing over 56 neuronal cell types that are highly replicable across analysis methods, sequencing technologies and modalities-is a comprehensive molecular and genomic account of the diverse neuronal and non-neuronal cell types in the mouse primary motor cortex. The atlas includes a population of excitatory neurons that resemble pyramidal cells in layer 4 in other cortical regions 4 . We further discovered thousands of concordant marker genes and gene regulatory elements for these cell types. Our results highlight the complex molecular regulation of cell types in the brain and will directly enable the design of reagents to target specific cell types in the mouse primary motor cortex for functional analysis., (© 2021. The Author(s).)

Light-dependent protochlorophyllide oxidoreductase (LPOR) and dark-operative protochlorophyllide oxidoreductase are evolutionary and structurally distinct enzymes that are essential for the synthesis of (bacterio)chlorophyll, the primary pigment needed for both anoxygenic and oxygenic photosynthesis. In contrast to the long-held hypothesis that LPORs are only present in oxygenic phototrophs, we recently identified a functional LPOR in the aerobic anoxygenic phototrophic bacterium (AAPB) Dinoroseobacter shibae and attributed its presence to a single horizontal gene transfer event from cyanobacteria. Here, we provide evidence for the more widespread presence of genuine LPOR enzymes in AAPBs. An exhaustive bioinformatics search identified 36 putative LPORs outside of oxygenic phototrophic bacteria (cyanobacteria) with the majority being AAPBs. Using in vitro and in vivo assays, we show that the large majority of the tested AAPB enzymes are genuine LPORs. Solution structural analyses, performed for two of the AAPB LPORs, revealed a globally conserved structure when compared with a well-characterized cyanobacterial LPOR. Phylogenetic analyses suggest that LPORs were transferred not only from cyanobacteria but also subsequently between proteobacteria and from proteobacteria to Gemmatimonadetes. Our study thus provides another interesting example for the complex evolutionary processes that govern the evolution of bacteria, involving multiple horizontal gene transfer events that likely occurred at different time points and involved different donors., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.)

The dynamics of CD4 + T cell memory development remain to be examined at genome scale. In malaria-endemic regions, antimalarial chemoprevention protects long after its cessation and associates with effects on CD4 + T cells. We applied single-cell RNA sequencing and computational modelling to track memory development during Plasmodium infection and treatment. In the absence of central memory precursors, two trajectories developed as T helper 1 (T H 1) and follicular helper T (T FH ) transcriptomes contracted and partially coalesced over three weeks. Progeny of single clones populated T H 1 and T FH trajectories, and fate-mapping suggested that there was minimal lineage plasticity. Relationships between T FH and central memory were revealed, with antimalarials modulating these responses and boosting T H 1 recall. Finally, single-cell epigenomics confirmed that heterogeneity among effectors was partially reset in memory. Thus, the effector-to-memory transition in CD4 + T cells is gradual during malaria and is modulated by antiparasitic drugs. Graphical user interfaces are presented for examining gene-expression dynamics and gene-gene correlations ( http://haquelab.mdhs.unimelb.edu.au/cd4_memory/ ).

The more than 1000 single-cell transcriptomics studies that have been published to date constitute a valuable and vast resource for biological discovery. While various 'atlas' projects have collated some of the associated datasets, most questions related to specific tissue types, species or other attributes of studies require identifying papers through manual and challenging literature search. To facilitate discovery with published single-cell transcriptomics data, we have assembled a near exhaustive, manually curated database of single-cell transcriptomics studies with key information: descriptions of the type of data and technologies used, along with descriptors of the biological systems studied. Additionally, the database contains summarized information about analysis in the papers, allowing for analysis of trends in the field. As an example, we show that the number of cell types identified in scRNA-seq studies is proportional to the number of cells analysed. Database URL: www.nxn.se/single-cell-studies/gui., (© The Author(s) 2020. Published by Oxford University Press.)

Hydrodynamic attractors have recently gained prominence in the context of early stages of ultrarelativistic heavy-ion collisions at the RHIC and LHC. We critically examine the existing ideas on this subject from a phase space point of view. In this picture the hydrodynamic attractor can be seen as a special case of the more general phenomenon of dynamical dimensionality reduction of phase space regions. We quantify this using principal component analysis. Furthermore, we adapt the well known slow-roll approximation to this setting. These techniques generalize easily to higher dimensional phase spaces, which we illustrate by a preliminary analysis of a dataset describing the evolution of a five-dimensional manifold of initial conditions immersed in a 16-dimensional representation of the phase space of the Boltzmann kinetic equation in the relaxation time approximation.

Acute gastrointestinal (GI) graft-versus-host disease (GVHD) is a primary determinant of mortality after allogeneic hematopoietic stem cell transplantation (alloSCT). The condition is mediated by alloreactive donor CD4+ T cells that differentiate into pathogenic subsets expressing IFN-γ, IL-17A, or GM-CSF and is regulated by subsets expressing IL-10 and/or Foxp3. Developmental relationships between Th cell states during priming in mesenteric lymph nodes (mLNs) and effector function in the GI tract remain undefined at genome scale. We applied scRNA-Seq and computational modeling to a mouse model of donor DC-mediated GVHD exacerbation, creating an atlas of putative CD4+ T cell differentiation pathways in vivo. Computational trajectory inference suggested emergence of pathogenic and regulatory states along a single developmental trajectory in mLNs. Importantly, we inferred an unexpected second trajectory, categorized by little proliferation or cytokine expression, reduced glycolysis, and high tcf7 expression. TCF1hi cells upregulated α4β7 before gut migration and failed to express cytokines. These cells exhibited recall potential and plasticity following secondary transplantation, including cytokine or Foxp3 expression, but reduced T cell factor 1 (TCF1). Thus, scRNA-Seq suggested divergence of alloreactive CD4+ T cells into quiescent and effector states during gut GVHD exacerbation by donor DC, reflecting putative heterogeneous priming in vivo. These findings, which are potentially the first at a single-cell level during GVHD over time, may assist in examination of T cell differentiation in patients undergoing alloSCT.

Motivation: Single-cell RNA-seq makes possible the investigation of variability in gene expression among cells, and dependence of variation on cell type. Statistical inference methods for such analyses must be scalable, and ideally interpretable., Results: We present an approach based on a modification of a recently published highly scalable variational autoencoder framework that provides interpretability without sacrificing much accuracy. We demonstrate that our approach enables identification of gene programs in massive datasets. Our strategy, namely the learning of factor models with the auto-encoding variational Bayes framework, is not domain specific and may be useful for other applications., Availability and Implementation: The factor model is available in the scVI package hosted at https://github.com/YosefLab/scVI/., Contact: v@nxn.se., Supplementary Information: Supplementary data are available at Bioinformatics online., (© The Author(s) 2020. Published by Oxford University Press.)

The simultaneous quantification of protein and RNA makes possible the inference of past, present, and future cell states from single experimental snapshots. To enable such temporal analysis from multimodal single-cell experiments, we introduce an extension of the RNA velocity method that leverages estimates of unprocessed transcript and protein abundances to extrapolate cell states. We apply the model to six datasets and demonstrate consistency among cell landscapes and phase portraits. The analysis software is available as the protaccel Python package.

The endothelial to haematopoietic transition (EHT) is the process whereby haemogenic endothelium differentiates into haematopoietic stem and progenitor cells (HSPCs). The intermediary steps of this process are unclear, in particular the identity of endothelial cells that give rise to HSPCs is unknown. Using single-cell transcriptome analysis and antibody screening, we identify CD44 as a marker of EHT enabling us to isolate robustly the different stages of EHT in the aorta-gonad-mesonephros (AGM) region. This allows us to provide a detailed phenotypical and transcriptional profile of CD44-positive arterial endothelial cells from which HSPCs emerge. They are characterized with high expression of genes related to Notch signalling, TGFbeta/BMP antagonists, a downregulation of genes related to glycolysis and the TCA cycle, and a lower rate of cell cycle. Moreover, we demonstrate that by inhibiting the interaction between CD44 and its ligand hyaluronan, we can block EHT, identifying an additional regulator of HSPC development.

Sesquiterpenoids are a large class of natural compounds offering manifold properties valuable for food, cosmetics, agriculture, and pharma industry. Production in microorganisms is a sustainable approach to provide sesquiterpenoids for research and industrial use independent of their natural sources. This requires the functional transfer of the respective biocatalytic pathways in an adequate host microorganism offering a sufficient supply of precursors that is ideally adjusted to the individual demand of the recombinant biosynthesis route. The phototrophic purple bacterium Rhodobacter capsulatus offers unique physiological properties that are favorable for biosynthesis of hydrophobic terpenes. Under phototrophic conditions, it develops a large intracytoplasmic membrane suitable for hosting membrane-bound enzymes and metabolites of respective biosynthetic pathways. In addition, Rhodobacter harbors an intrinsic carotenoid biosynthesis that can be engineered toward the production of foreign terpenes. Here, we evaluate R. capsulatus as host for the production of plant sesquiterpenoids under phototrophic conditions using patchoulol and valencene as a proof of concept. The heterologous expression of patchoulol synthase PcPS from Pogostemon cablin as well as the valencene synthases CsVS from Citrus sinensis and CnVS from Callitropsis nootkatensis led to the production of the respective sesquiterpenoids in R. capsulatus . To analyze, if gradually adjustable formation of the key precursor farnesylpyrophosphate (FPP) is beneficial for sesquiterpene synthesis under phototrophic conditions, the intrinsic 1-deoxy-D-xylulose 5-phosphate (DXP) pathway genes as well as the heterologous mevalonate pathway genes were modularly expressed in various combinations. To this end, different plasmids and chromosomally integrated expression tools were developed harboring the strong and tightly controlled P nif promoter for heterologous gene expression. Notably, comparative studies identified a distinct combination of precursor biosynthetic genes as best-performing setup for each of the tested sesquiterpene synthases. In summary, we could demonstrate that R. capsulatus is a promising alternative platform organism that is suited for sustainable sesquiterpenoid formation under phototrophic cultivation conditions. A modular engineering of R. capsulatus strains via tailored co-expression of FPP biosynthetic genes further allowed adaptation of sesquiterpene precursor formation to its catalytic conversion by different plant terpene synthases.

Aim: To study the sleep development and sleep characteristics in children at different obesity risks, based on parental weight, and also to explore their weekday-weekend sleep variations and associated family factors., Methods: A total of 145 children participating in a longitudinal obesity prevention project were included, of which 37 had normal-weight parents (low obesity risk), and 108 had overweight/obese parents (high obesity risk). Sleep diaries at ages 1 and 2 years were used to study sleep development in children at different obesity risks. Objectively assessed sleep using an accelerometer at 2 years of age was used to analyse weekday-weekend sleep variations., Results: There was no difference in sleep development from age 1 to age 2 among children at different obesity risks, but more children in the high-risk group had prolonged sleep onset latency and low sleep efficiency. At 2 years of age, children in the high-risk group had more weekday-weekend variation in sleep offset (mean difference 18 min, 95% confidence interval (CI) 4-33 min), midpoint of sleep (mean difference 14 min, 95% CI 3-25 min) and nap onset (mean difference 42 min, 95% CI 10-74 min) than children in the low-risk group, after adjusting for other family factors. However, no difference could be detected between groups in weekday-weekend variation in sleep duration., Conclusions: Unfavourable sleep characteristics, as well as more variation in sleep schedules, have been observed in children at high obesity risk. While the differences were relatively small, they may reflect the unfavourable sleep hygiene in families at high obesity risk., (© 2018 The Authors. Journal of Paediatrics and Child Health published by John Wiley & Sons Australia, Ltd on behalf of Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

Applying a kinetic model of RNA transcription and splicing, La Manno et al. (2018) predict changes in mRNA levels of individual cells from single-cell RNA-seq data., (Copyright © 2018. Published by Elsevier Inc.)

Technological advances have made it possible to measure spatially resolved gene expression at high throughput. However, methods to analyze these data are not established. Here we describe SpatialDE, a statistical test to identify genes with spatial patterns of expression variation from multiplexed imaging or spatial RNA-sequencing data. SpatialDE also implements 'automatic expression histology', a spatial gene-clustering approach that enables expression-based tissue histology.

Measurement of the transcriptomes of single cells has been feasible for only a few years, but it has become an extremely popular assay. While many types of analysis can be carried out and various questions can be answered by single-cell RNA-seq, a central focus is the ability to survey the diversity of cell types in a sample. Unbiased and reproducible cataloging of gene expression patterns in distinct cell types requires large numbers of cells. Technological developments and protocol improvements have fueled consistent and exponential increases in the number of cells that can be studied in single-cell RNA-seq analyses. In this Perspective, we highlight the key technological developments that have enabled this growth in the data obtained from single-cell RNA-seq experiments.

The crucial capability of T cells for discrimination between self and non-self peptides is based on negative selection of developing thymocytes by medullary thymic epithelial cells (mTECs). The mTECs purge autoreactive T cells by expression of cell-type specific genes referred to as tissue-restricted antigens (TRAs). Although the autoimmune regulator (AIRE) protein is known to promote the expression of a subset of TRAs, its mechanism of action is still not fully understood. The expression of TRAs that are not under the control of AIRE also needs further characterization. Furthermore, expression patterns of TRA genes have been suggested to change over the course of mTEC development. Herein we have used single-cell RNA-sequencing to resolve patterns of TRA expression during mTEC development. Our data indicated that mTEC development consists of three distinct stages, correlating with previously described jTEC, mTEChi and mTEClo phenotypes. For each subpopulation, we have identified marker genes useful in future studies. Aire-induced TRAs were switched on during jTEC-mTEC transition and were expressed in genomic clusters, while otherwise the subsets expressed largely overlapping sets of TRAs. Moreover, population-level analysis of TRA expression frequencies suggested that such differences might not be necessary to achieve efficient thymocyte selection.

Purpose: Childhood obesity represents a social burden. This study aims to investigate whether achieved educational level differs in young adults who have suffered obesity in childhood compared with the general population and to determine how obesity treatment influences achieved educational level., Methods: This prospective cohort study includes subjects from the Swedish Childhood Obesity Treatment Registry (BORIS, n = 1,465) who were followed up after 20 years of age. They were compared with a randomly selected matched population-based group (n = 6,979). Achieved educational level was defined as ≥12 years in school (completers). Covariates include sex, migration background, and attention deficit disorders for both groups. Furthermore, age and degree of obesity at start of obesity treatment, treatment duration, and efficacy were analyzed in the obese cohort., Results: In the obese cohort, 55.4% were school completers, compared with 76.2% in the comparison group (adjusted odds ratio [OR] = .42, p < .0001). Subjects with moderate obesity had a completion rate of 64.4%, compared with 50.9% among subjects with morbid obesity (adjusted OR = .57, p < .0001). Successful obesity treatment was associated with increased future educational level, compared with those experiencing no treatment effect (61.9% vs. 51.3% completers; adjusted OR = 1.4, p < .05). In children with attention deficit disorder, obesity was not an extra risk for not completing 12 or more years of schooling, p = .11., Conclusions: Obesity in childhood was associated with low educational level in early adulthood. Children and adolescents with obesity may require special support at school in addition to health care treatment to lose weight., (Copyright © 2017 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)