Mouse Genome Informatics: an integrated knowledgebase system for the laboratory mouse.

Mouse Genome Informatics (MGI) is a federation of expertly curated information resources designed to support experimental and computational investigations into genetic and genomic aspects of human biology and disease using the laboratory mouse as a model system. The Mouse Genome Database (MGD) and the Gene Expression Database (GXD) are core MGI databases that share data and system architecture. MGI serves as the central community resource of integrated information about mouse genome features, variation, expression, gene function, phenotype, and human disease models acquired from peer-reviewed publications, author submissions, and major bioinformatics resources. To facilitate integration and standardization of data, biocuration scientists annotate using terms from controlled metadata vocabularies and biological ontologies (e.g. Mammalian Phenotype Ontology, Mouse Developmental Anatomy, Disease Ontology, Gene Ontology, etc.), and by applying international community standards for gene, allele, and mouse strain nomenclature. MGI serves basic scientists, translational researchers, and data scientists by providing access to FAIR-compliant data in both human-readable and compute-ready formats. The MGI resource is accessible at https://informatics.jax.org. Here, we present an overview of the core data types represented in MGI and highlight recent enhancements to the resource with a focus on new data and functionality for MGD and GXD.

The role of mother's and child's self-regulation on bidirectional links between harsh parenting and child externalizing problems.

The authors examined task-based (i.e., executive function), surveyed (i.e., effortful control), and physiological (i.e., resting cardiac respiratory sinus arrhythmia [RSA]) measures of child and maternal regulation as distinct moderators of longitudinal bidirectional links between child externalizing (EXT) behaviors and harsh parenting (HP) from 6 to 9 years. The sample size was 299 (50.9% female; 1% Asian, 4% multiple races; 14% Black; 78% White), and participants were recruited in the United States (a rural college town in Virginia and a midsized city in North Carolina). Higher child EXT at 6 years predicted higher HP at 7-8 years, which predicted higher EXT at 9 years. Also, this path was moderated by 6-year child effortful control, 6-year resting RSA, and 9-year executive function. In contrast, there was no moderating effect of any measure of maternal regulation. Findings suggest it is important to consider child self-regulation when examining bidirectionality in parent and child effects for HP and child EXT. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Biochemical pathways represented by Gene Ontology-Causal Activity Models identify distinct phenotypes resulting from mutations in pathways.

Gene inactivation can affect the process(es) in which that gene acts and causally downstream ones, yielding diverse mutant phenotypes. Identifying the genetic pathways resulting in a given phenotype helps us understand how individual genes interact in a functional network. Computable representations of biological pathways include detailed process descriptions in the Reactome Knowledgebase and causal activity flows between molecular functions in Gene Ontology-Causal Activity Models (GO-CAMs). A computational process has been developed to convert Reactome pathways to GO-CAMs. Laboratory mice are widely used models of normal and pathological human processes. We have converted human Reactome GO-CAMs to orthologous mouse GO-CAMs, as a resource to transfer pathway knowledge between humans and model organisms. These mouse GO-CAMs allowed us to define sets of genes that function in a causally connected way. To demonstrate that individual variant genes from connected pathways result in similar but distinguishable phenotypes, we used the genes in our pathway models to cross-query mouse phenotype annotations in the Mouse Genome Database (MGD). Using GO-CAM representations of 2 related but distinct pathways, gluconeogenesis and glycolysis, we show that individual causal paths in gene networks give rise to discrete phenotypic outcomes resulting from perturbations of glycolytic and gluconeogenic genes. The accurate and detailed descriptions of gene interactions recovered in this analysis of well-studied processes suggest that this strategy can be applied to less well-understood processes in less well-studied model systems to predict phenotypic outcomes of novel gene variants and to identify potential gene targets in altered processes.

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.

Biochemical Pathways Represented by Gene Ontology Causal Activity Models Identify Distinct Phenotypes Resulting from Mutations in Pathways.

Gene inactivation can affect the process(es) in which that gene acts and causally downstream ones, yielding diverse mutant phenotypes. Identifying the genetic pathways resulting in a given phenotype helps us understand how individual genes interact in a functional network. Computable representations of biological pathways include detailed process descriptions in the Reactome Knowledgebase, and causal activity flows between molecular functions in Gene Ontology-Causal Activity Models (GO-CAMs). A computational process has been developed to convert Reactome pathways to GO-CAMs. Laboratory mice are widely used models of normal and pathological human processes. We have converted human Reactome GO-CAMs to orthologous mouse GO-CAMs, as a resource to transfer pathway knowledge between humans and model organisms. These mouse GO-CAMs allowed us to define sets of genes that function in a connected and well-defined way. To test whether individual genes from well-defined pathways result in similar and distinguishable phenotypes, we used the genes in our pathway models to cross-query mouse phenotype annotations in the Mouse Genome Database (MGD). Using GO-CAM representations of two related but distinct pathways, gluconeogenesis and glycolysis, we can identify causal paths in gene networks that give rise to discrete phenotypic outcomes for perturbations of glycolysis and gluconeogenesis. The accurate and detailed descriptions of gene interactions recovered in this analysis of well-studied processes suggest that this strategy can be applied to less well-understood processes in less well-studied model systems to predict phenotypic outcomes of novel gene variants and to identify potential gene targets in altered processes.

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.

Longitudinal bidirectional relations between children's negative affectivity and maternal emotion expressivity.

Although children's negative affectivity is a temperamental characteristic that is biologically based, it is framed within and shaped by their emotional environments which are partly created by maternal emotion expressivity in the family. Children, in turn, play a role in shaping their family emotional context, which could lead to changes in mothers' emotion expressivity in the family. However, these theorized longitudinal bidirectional relations between child negative affectivity and maternal positive and negative expressivity have not been studied from toddlerhood to early school-age. The current study utilized a cross-lagged panel model to examine the reciprocal relations between children's negative affectivity and maternal expressivity within the family over the course of early childhood. Participants were 140 mother-child dyads (72 boys, mean age = 2.67 years, primarily White). Mothers reported the positive and negative expressivity in the family and children's negative affectivity in toddlerhood (T1), preschool (T2), and school-age (T3). Maternal negative expressivity and child negative affectivity at T1 were significantly correlated. Maternal negative expressivity at T1 significantly predicted child negative affectivity at T3. Children's negative affectivity at T2 significantly predicted mothers' negative expressivity at T3. Mothers' positive expressivity was not related to children's negative affectivity at any of the three time points. The findings demonstrate the reciprocal relations between children's negative affectivity and maternal negative expressivity in the family, suggesting the importance of the interplay between child temperament and maternal expressivity within the family emotional context.

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.

Advances in Behavioral Remote Data Collection in the Home Setting: Assessing the Mother-Infant Relationship and Infant's Adaptive Behavior via Virtual Visits.

Psychological science is struggling with moving forward in the midst of the COVID-19 pandemic, especially due to the halting of behavioral data collection in the laboratory. Safety barriers to assessing psychological behavior in person increased the need for remote data collection in natural settings. In response to these challenges, researchers, including our team, have utilized this time to advance remote behavioral methodology. In this article, we provide an overview of our group's strategies for remote data collection methodology and examples from our research in collecting behavioral data in the context of psychological functioning. Then, we describe the design and development of our strategies for remote data collection of mother-infant interactions, with the goal being to assess maternal sensitivity and intrusiveness, as well as infants' adaptive behaviors in several developmental domains. During these virtual visits over Zoom, mother-infant dyads watched a book-reading video and were asked to participate in peek-a-boo, toy play, and toy removal tasks. After the behavioral tasks, a semi-structured interview (Vineland Adaptive Behavior Scale - VABS III) was conducted to assess the infant's adaptive behavior in communication, socialization, daily living skills, and motor domains. We delineate the specific strategies we applied to integrate laboratory tasks and a semi-structured interview into remote data collection in home settings with mothers and infants. We also elaborate on issues encountered during remote data collection and how we resolved these challenges. Lastly, to inform protocols for future remote data collection, we address considerations and recommendations, as well as benefits and future directions for behavioral researchers in developmental psychology research.

Why do parents use screen media with toddlers? The role of child temperament and parenting stress in early screen use.

Considering child characteristics may be an important piece to understanding parental decision-making for children's screen use. The current cross-sectional study examined the mediating role of maternal parenting stress in the relation of child temperament to young children's screen use. Recognizing the multidimensional aspects of temperament, three mediated pathways for three temperament domains (i.e., negative affectivity, surgency, and effortful control) were tested. Mothers of toddlers, 18-36 months (N = 296), completed an online survey, reporting on child temperament, total parenting stress, and child screen use. The results showed that mother-child dynamics were related to toddlers' screen use. Toddlers' negative affectivity and effortful control were each associated with toddlers' screen use through maternal parenting stress. Higher negative affectivity was associated with higher maternal parenting stress, which in turn, was related to greater screen use in toddlers. Toddlers' lower effortful control was related to higher maternal parenting stress, which in turn, was associated with greater screen use. Toddlers' surgency was not related to either maternal parenting stress or toddlers' screen use. The findings from this study contribute to an understanding of media-related parenting in toddlerhood and may help with the development of strategies for supporting healthy media habits in families with young children.

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.

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.