Changes in children's anger, sadness, and persistence across blocked goals: Implications for self-regulation.

The current study took a person-centered approach to examine the heterogeneity of changes in children's emotions and persistence during a goal-blocking task and examined how different profiles of emotions and persistence related to children's self-regulation. Children's anger, sadness, and persistence were rated in a goal-blocking task in toddlerhood (T1; N = 140, 72 boys, Mage  = 2.67 years, 90.7% White) and preschool (T2). Children's self-regulation, specifically sustained attention and engagement, was assessed at T1, T2, and early school-age (T3) from 2005 to 2012. Growth mixture modeling revealed two classes of children at T1 and three classes at T2 with different patterns of anger, sadness, and persistence. Children's classification at T2, but not T1, significantly predicted their sustained attention and engagement both concurrently and longitudinally.

Developmental patterns of children's shyness: Relations with physiological, emotional, and regulatory responses to being treated unfairly.

The dysregulation of social fear has been widely studied in children's shyness, but we know little about how shy children regulate during unfair treatment. We first characterized developmental patterns of children's shyness (N = 304, ngirls = 153; 74% White, 26% Other) across 2 (Mage = 2.07), 3 (Mage = 3.08), 4 (Mage = 4.08), and 6 (Mage = 6.58) years of age. Data collection occurred from 2007 to 2014. At age 6, the high stable group had higher cardiac vagal withdrawal and lower expressed sadness and approach-related regulatory strategy than the low stable group when being treated unfairly. Although shy children may be more physiologically impacted by being treated unfairly, they may mask their sadness to signal appeasement.

Mouse Genome Database (MGD): Knowledgebase for mouse-human comparative biology.

The Mouse Genome Database (MGD; http://www.informatics.jax.org) is the community model organism knowledgebase for the laboratory mouse, a widely used animal model for comparative studies of the genetic and genomic basis for human health and disease. MGD is the authoritative source for biological reference data related to mouse genes, gene functions, phenotypes and mouse models of human disease. MGD is the primary source for official gene, allele, and mouse strain nomenclature based on the guidelines set by the International Committee on Standardized Nomenclature for Mice. MGD's biocuration scientists curate information from the biomedical literature and from large and small datasets contributed directly by investigators. In this report we describe significant enhancements to the content and interfaces at MGD, including (i) improvements in the Multi Genome Viewer for exploring the genomes of multiple mouse strains, (ii) inclusion of many more mouse strains and new mouse strain pages with extended query options and (iii) integration of extensive data about mouse strain variants. We also describe improvements to the efficiency of literature curation processes and the implementation of an information portal focused on mouse models and genes for the study of COVID-19.

Annotated expression and activity data for murine recombinase alleles and transgenes: the CrePortal resource.

Recombinase alleles and transgenes can be used to facilitate spatio-temporal specificity of gene disruption or transgene expression. However, the versatility of this in vivo recombination system relies on having detailed and accurate characterization of recombinase expression and activity to enable selection of the appropriate allele or transgene. The CrePortal ( http://www.informatics.jax.org/home/recombinase ) leverages the informatics infrastructure of Mouse Genome Informatics to integrate data from the scientific literature, direct data submissions from the scientific community at-large, and from major projects developing new recombinase lines and characterizing recombinase expression and specificity patterns. Searching the CrePortal by recombinase activity or specific recombinase gene driver provides users with a recombinase alleles and transgenes activity tissue summary and matrix comparison of gene expression and recombinase activity with links to generation details, a recombinase activity grid, and associated phenotype annotations. Future improvements will add cell type-based activity annotations. The CrePortal provides a comprehensive presentation of recombinase allele and transgene data to assist researchers in selection of the recombinase allele or transgene based on where and when recombination is desired.

Global genetic analysis in mice unveils central role for cilia in congenital heart disease.

Congenital heart disease (CHD) is the most prevalent birth defect, affecting nearly 1% of live births; the incidence of CHD is up to tenfold higher in human fetuses. A genetic contribution is strongly suggested by the association of CHD with chromosome abnormalities and high recurrence risk. Here we report findings from a recessive forward genetic screen in fetal mice, showing that cilia and cilia-transduced cell signalling have important roles in the pathogenesis of CHD. The cilium is an evolutionarily conserved organelle projecting from the cell surface with essential roles in diverse cellular processes. Using echocardiography, we ultrasound scanned 87,355 chemically mutagenized C57BL/6J fetal mice and recovered 218 CHD mouse models. Whole-exome sequencing identified 91 recessive CHD mutations in 61 genes. This included 34 cilia-related genes, 16 genes involved in cilia-transduced cell signalling, and 10 genes regulating vesicular trafficking, a pathway important for ciliogenesis and cell signalling. Surprisingly, many CHD genes encoded interacting proteins, suggesting that an interactome protein network may provide a larger genomic context for CHD pathogenesis. These findings provide novel insights into the potential Mendelian genetic contribution to CHD in the fetal population, a segment of the human population not well studied. We note that the pathways identified show overlap with CHD candidate genes recovered in CHD patients, suggesting that they may have relevance to the more complex genetics of CHD overall. These CHD mouse models and >8,000 incidental mutations have been sperm archived, creating a rich public resource for human disease modelling.

Mouse Genome Database (MGD) 2019.

The Mouse Genome Database (MGD; http://www.informatics.jax.org) is the community model organism genetic and genome resource for the laboratory mouse. MGD is the authoritative source for biological reference data sets related to mouse genes, gene functions, phenotypes, and mouse models of human disease. MGD is the primary outlet for official gene, allele and mouse strain nomenclature based on the guidelines set by the International Committee on Standardized Nomenclature for Mice. In this report we describe significant enhancements to MGD, including two new graphical user interfaces: (i) the Multi Genome Viewer for exploring the genomes of multiple mouse strains and (ii) the Phenotype-Gene Expression matrix which was developed in collaboration with the Gene Expression Database (GXD) and allows researchers to compare gene expression and phenotype annotations for mouse genes. Other recent improvements include enhanced efficiency of our literature curation processes and the incorporation of Transcriptional Start Site (TSS) annotations from RIKEN's FANTOM 5 initiative.

The mouse Gene Expression Database (GXD): 2019 update.

The mouse Gene Expression Database (GXD) is an extensive, well-curated community resource freely available at www.informatics.jax.org/expression.shtml. Covering all developmental stages, GXD includes data from RNA in situ hybridization, immunohistochemistry, RT-PCR, northern blot and western blot experiments in wild-type and mutant mice. GXD's gene expression information is integrated with the other data in Mouse Genome Informatics and interconnected with other databases, placing these data in the larger biological and biomedical context. Since the last report, the ability of GXD to provide insights into the molecular mechanisms of development and disease has been greatly enhanced by the addition of new data and by the implementation of new web features. These include: improvements to the Differential Gene Expression Data Search, facilitating searches for genes that have been shown to be exclusively expressed in a specified structure and/or developmental stage; an enhanced anatomy browser that now provides access to expression data and phenotype data for a given anatomical structure; direct access to the wild-type gene expression data for the tissues affected in a specific mutant; and a comparison matrix that juxtaposes tissues where a gene is normally expressed against tissues, where mutations in that gene cause abnormalities.

Mouse Genome Database (MGD)-2018: knowledgebase for the laboratory mouse.

The Mouse Genome Database (MGD; http://www.informatics.jax.org) is the key community mouse database which supports basic, translational and computational research by providing integrated data on the genetics, genomics, and biology of the laboratory mouse. MGD serves as the source for biological reference data sets related to mouse genes, gene functions, phenotypes and disease models with an increasing emphasis on the association of these data to human biology and disease. We report here on recent enhancements to this resource, including improved access to mouse disease model and human phenotype data and enhanced relationships of mouse models to human disease.

Context of Maternal Intrusiveness During Infancy and Associations with Preschool Executive Function.

The relation between maternal behavior and neurocognitive development is complex and may depend on the task context. We examined 5-month-old infant frontal EEG, maternal intrusiveness (MI) evaluated during two play contexts at 5 and 10 months, and a battery of executive function (EF) tasks completed at 48 months to evaluate if MI during infancy and infant neural function interacted to predict later cognition. Infant frontal EEG was a predictor of 4-year EF. MI during structured play at both 5 and 10 months predicted preschool EF, and MI during unstructured did not have a main effect on EF but showed a potential moderating effect of infant EEG on later EF. The pattern changed between ages, with MI during structured play at 5 months showing a positive association with age 4 EF, whereas MI during structured play at 10 months had a negative association with age 4 EF. We demonstrate differences in the context of maternal behavior used to predict childhood EF, highlighting the importance of considering parenting context in EF development.

Parenting and Children's Executive Function Stability Across the Transition to School.

When children transition to school between the ages of 4 and 6 years, they must learn to control their attention and behavior to be successful. Concurrently, executive function (EF) is an important skill undergoing significant development in childhood. To understand changes occurring during this period, we examined the role of parenting in the development of children's EF from 4 to 6 years old. Participants were mother and child dyads (N = 151). Children completed cognitive tasks to assess overall EF at age 4 and age 6. At both time points, mothers and children completed interaction tasks which were videotaped and coded to assess various parenting dimensions. Results indicated that children with high EF at age 4 were more likely to have high EF at age 6. In addition, results suggested that higher levels of positive parenting across the transition to school promote stability of individual differences in EF.

Maternal behaviors in toddlerhood as predictors of children's private speech in preschool.

Private speech is an important strategy reflecting children's self-regulation, and thus understanding how parenting may support private speech can inform intervention work on improving self-regulation. The current study longitudinally investigated how sensitive parenting and directive parenting in toddlerhood interacted to predict preschoolers' private speech in an emotion-eliciting task. In toddlerhood, maternal parenting behaviors were observed during two freeplay sessions. Preschoolers' social and private speech were transcribed and coded during a frustration task. Whereas parenting did not relate to other forms of private speech, preschoolers' facilitative task-relevant private speech was predicted by the interaction of mothers' sensitive and directive behaviors. When sensitivity was high, parents who were less directive had children who used more facilitative task-relevant private speech. These findings highlight that children's regulation may be supported through the combination of high sensitivity and low directiveness when parents and children are engaged in unstructured play together.

Mouse Genome Database (MGD)-2017: community knowledge resource for the laboratory mouse.

The Mouse Genome Database (MGD: http://www.informatics.jax.org) is the primary community data resource for the laboratory mouse. It provides a highly integrated and highly curated system offering a comprehensive view of current knowledge about mouse genes, genetic markers and genomic features as well as the associations of those features with sequence, phenotypes, functional and comparative information, and their relationships to human diseases. MGD continues to enhance access to these data, to extend the scope of data content and visualizations, and to provide infrastructure and user support that ensures effective and efficient use of MGD in the advancement of scientific knowledge. Here, we report on recent enhancements made to the resource and new features.

The Human Phenotype Ontology in 2017.

Deep phenotyping has been defined as the precise and comprehensive analysis of phenotypic abnormalities in which the individual components of the phenotype are observed and described. The three components of the Human Phenotype Ontology (HPO; www.human-phenotype-ontology.org) project are the phenotype vocabulary, disease-phenotype annotations and the algorithms that operate on these. These components are being used for computational deep phenotyping and precision medicine as well as integration of clinical data into translational research. The HPO is being increasingly adopted as a standard for phenotypic abnormalities by diverse groups such as international rare disease organizations, registries, clinical labs, biomedical resources, and clinical software tools and will thereby contribute toward nascent efforts at global data exchange for identifying disease etiologies. This update article reviews the progress of the HPO project since the debut Nucleic Acids Research database article in 2014, including specific areas of expansion such as common (complex) disease, new algorithms for phenotype driven genomic discovery and diagnostics, integration of cross-species mapping efforts with the Mammalian Phenotype Ontology, an improved quality control pipeline, and the addition of patient-friendly terminology.

Function of child anger and sadness in response to a blocked goal.

Drawing from the functional theory of emotion, anger is proposed to serve adaptive functions such as motivating children to persist in overcoming difficulties to achieve their goals, whereas sadness helps children to shift attention away from goals that they determine cannot be attained. Despite the theorized importance of anger to persistence, it does not always relate to persistence in expected ways empirically; the role that sadness might play in how anger relates to persistence is often not considered even though children often experience both anger and sadness when goals are blocked. We hypothesized that how anger relates to persistence would depend on the level of sadness that children felt and, thus, tested sadness as a moderator of the relation of anger to persistence. We expected that the relation of anger to persistence would be stronger when sadness is lower. Child anger, sadness, and persistence were observed in a locked-box frustration task when children were 4 or 5 years old (N = 116). Although higher levels of child anger were associated with more persistence, the association between anger and persistence was stronger when sadness was lower than when sadness was higher. The findings indicate that children's ability to use the motivational aspects of anger to promote persistence may depend on the levels of sadness felt.

Naming CRISPR alleles: endonuclease-mediated mutation nomenclature across species.

The widespread use of CRISPR/Cas and other targeted endonuclease technologies in many species has led to an explosion in the generation of new mutations and alleles. The ability to generate many different mutations from the same target sequence either by homology-directed repair with a donor sequence or non-homologous end joining-induced insertions and deletions necessitates a means for representing these mutations in literature and databases. Standardized nomenclature can be used to generate unambiguous, concise, and specific symbols to represent mutations and alleles. The research communities of a variety of species using CRISPR/Cas and other endonuclease-mediated mutation technologies have developed different approaches to naming and identifying such alleles and mutations. While some organism-specific research communities have developed allele nomenclature that incorporates the method of generation within the official allele or mutant symbol, others use metadata tags that include method of generation or mutagen. Organism-specific research community databases together with organism-specific nomenclature committees are leading the way in providing standardized nomenclature and metadata to facilitate the integration of data from alleles and mutations generated using CRISPR/Cas and other targeted endonucleases.

Infant frontal electroencephalogram asymmetry and negative emotional reactivity as predictors of toddlerhood effortful control.

Given the importance of children's self-regulation, relations were examined between two fundamental components of self-regulation, specifically temperamentally based reactivity and regulation. Infant negative emotional reactivity and regulation, measured via frontal electroencephalogram (EEG) asymmetry, were examined as potential precursors to understanding toddlerhood regulation, conceptualized as effortful control. Our longitudinal design allowed for examination of two perspectives on the interplay of reactivity and regulation, namely that (a) early negative affectivity interferes with the development of later regulation and (b) regulation is necessary to modulate negative affectivity and, thus, would buffer the effects of negative affectivity on later regulation. Mother-child dyads participated in a three-wave longitudinal study. Baseline frontal EEG asymmetry was assessed at 10months (T1). Mothers rated children's negative reactivity at both 10 and 24months (T2). Children's effortful control, measured at 30-36months (T3), was a composite score of maternal ratings and observed behavior during a snack delay. Negative affectivity was related to effortful control; however, significant interactions between negative affect and frontal EEG asymmetry were found. Higher levels of negative affectivity at both T1 and T2 were associated with lower levels of effortful control at T3, but only for toddlers who also had right frontal EEG asymmetry. Negative affectivity was not associated with effortful control for the left frontal EEG asymmetry group. Our moderation findings highlight the complex relations of negative affect and frontal EEG asymmetry in understanding children's development of self-regulation, specifically effortful control. The interaction between early reactivity and physiological regulation indicates that both may be important precursors of effortful control.

The Human Phenotype Ontology project: linking molecular biology and disease through phenotype data.

The Human Phenotype Ontology (HPO) project, available at http://www.human-phenotype-ontology.org, provides a structured, comprehensive and well-defined set of 10,088 classes (terms) describing human phenotypic abnormalities and 13,326 subclass relations between the HPO classes. In addition we have developed logical definitions for 46% of all HPO classes using terms from ontologies for anatomy, cell types, function, embryology, pathology and other domains. This allows interoperability with several resources, especially those containing phenotype information on model organisms such as mouse and zebrafish. Here we describe the updated HPO database, which provides annotations of 7,278 human hereditary syndromes listed in OMIM, Orphanet and DECIPHER to classes of the HPO. Various meta-attributes such as frequency, references and negations are associated with each annotation. Several large-scale projects worldwide utilize the HPO for describing phenotype information in their datasets. We have therefore generated equivalence mappings to other phenotype vocabularies such as LDDB, Orphanet, MedDRA, UMLS and phenoDB, allowing integration of existing datasets and interoperability with multiple biomedical resources. We have created various ways to access the HPO database content using flat files, a MySQL database, and Web-based tools. All data and documentation on the HPO project can be found online.

Mouse Genome Database: From sequence to phenotypes and disease models.

The Mouse Genome Database (MGD, www.informatics.jax.org) is the international scientific database for genetic, genomic, and biological data on the laboratory mouse to support the research requirements of the biomedical community. To accomplish this goal, MGD provides broad data coverage, serves as the authoritative standard for mouse nomenclature for genes, mutants, and strains, and curates and integrates many types of data from literature and electronic sources. Among the key data sets MGD supports are: the complete catalog of mouse genes and genome features, comparative homology data for mouse and vertebrate genes, the authoritative set of Gene Ontology (GO) annotations for mouse gene functions, a comprehensive catalog of mouse mutations and their phenotypes, and a curated compendium of mouse models of human diseases. Here, we describe the data acquisition process, specifics about MGD's key data areas, methods to access and query MGD data, and outreach and user help facilities.

Allele, phenotype and disease data at Mouse Genome Informatics: improving access and analysis.

A core part of the Mouse Genome Informatics (MGI) resource is the collection of mouse mutations and the annotation phenotypes and diseases displayed by mice carrying these mutations. These data are integrated with the rest of data in MGI and exported to numerous other resources. The use of mouse phenotype data to drive translational research into human disease has expanded rapidly with the improvements in sequencing technology. MGI has implemented many improvements in allele and phenotype data annotation, search, and display to facilitate access to these data through multiple avenues. For example, the description of alleles has been modified to include more detailed categories of allele attributes. This allows improved discrimination between mutation types. Further, connections have been created between mutations involving multiple genes and each of the genes overlapping the mutation. This allows users to readily find all mutations affecting a gene and see all genes affected by a mutation. In a similar manner, the genes expressed by transgenic or knock-in alleles are now connected to these alleles. The advanced search forms and public reports have been updated to take advantage of these improvements. These search forms and reports are used by an expanding number of researchers to identify novel human disease genes and mouse models of human disease.