Confidence and barriers: Analysis of factors associated with timely routine childhood vaccination in Canada during the COVID-19 pandemic.

Routine childhood vaccination is a crucial component of public health in Canada and worldwide. To facilitate catch-up from the global decline in routine vaccination caused by the COVID-19 pandemic, and toward the ongoing pursuit of coverage goals, vaccination programs must understand barriers to vaccine access imposed or exacerbated by the pandemic. We conducted a regionally representative online survey in January 2023 including 2036 Canadian parents with children under the age of 18.

Systemic interindividual epigenetic variation in humans is associated with transposable elements and under strong genetic control.

Background: Genetic variants can modulate phenotypic outcomes via epigenetic intermediates, for example at methylation quantitative trait loci (mQTL). We present the first large-scale assessment of mQTL at human genomic regions selected for interindividual variation in CpG methylation, which we call correlated regions of systemic interindividual variation (CoRSIVs). These can be assayed in blood DNA and do not reflect interindividual variation in cellular composition.

Sex-specific epigenetic development in the mouse hypothalamic arcuate nucleus pinpoints human genomic regions associated with body mass index.

Recent genome-wide association studies corroborate classical research on developmental programming indicating that obesity is primarily a neurodevelopmental disease strongly influenced by nutrition during critical ontogenic windows. Epigenetic mechanisms regulate neurodevelopment; however, little is known about their role in establishing and maintaining the brain's energy balance circuitry. We generated neuron and glia methylomes and transcriptomes from male and female mouse hypothalamic arcuate nucleus, a key site for energy balance regulation, at time points spanning the closure of an established critical window for developmental programming of obesity risk.

A machine learning case-control classifier for schizophrenia based on DNA methylation in blood.

Epigenetic dysregulation is thought to contribute to the etiology of schizophrenia (SZ), but the cell type-specificity of DNA methylation makes population-based epigenetic studies of SZ challenging. To train an SZ case-control classifier based on DNA methylation in blood, therefore, we focused on human genomic regions of systemic interindividual epigenetic variation (CoRSIVs), a subset of which are represented on the Illumina Human Methylation 450K (HM450) array. HM450 DNA methylation data on whole blood of 414 SZ cases and 433 non-psychiatric controls were used as training data for a classification algorithm with built-in feature selection, sparse partial least squares discriminate analysis (SPLS-DA); application of SPLS-DA to HM450 data has not been previously reported.

Contribution of growth hormone secretagogue receptor (GHSR) signaling in the ventral tegmental area (VTA) to the regulation of social motivation in male mice.

Most psychiatric disorders are characterized by deficits in the ability to interact socially with others. Ghrelin, a hormone normally associated with the regulation of glucose utilization and appetite, is also implicated in the modulation of motivated behaviors including those associated with food and sex rewards. Here we hypothesized that deficits in ghrelin receptor (growth hormone secretagogue receptor; GHSR) signaling are also associated with deficits in social motivation in male mice.

Identification of cell type-specific methylation signals in bulk whole genome bisulfite sequencing data.

Background: The traditional approach to studying the epigenetic mechanism CpG methylation in tissue samples is to identify regions of concordant differential methylation spanning multiple CpG sites (differentially methylated regions). Variation limited to single or small numbers of CpGs has been assumed to reflect stochastic processes. To test this, we developed software, Cluster-Based analysis of CpG methylation (CluBCpG), and explored variation in read-level CpG methylation patterns in whole genome bisulfite sequencing data.

DNA methylation in AgRP neurons regulates voluntary exercise behavior in mice.

DNA methylation regulates cell type-specific gene expression. Here, in a transgenic mouse model, we show that deletion of the gene encoding DNA methyltransferase Dnmt3a in hypothalamic AgRP neurons causes a sedentary phenotype characterized by reduced voluntary exercise and increased adiposity. Whole-genome bisulfite sequencing (WGBS) and transcriptional profiling in neuronal nuclei from the arcuate nucleus of the hypothalamus (ARH) reveal differentially methylated genomic regions and reduced expression of AgRP neuron-associated genes in knockout mice.

S100a4-Cre-mediated deletion of Patched1 causes hypogonadotropic hypogonadism: role of pituitary hematopoietic cells in endocrine regulation.

Hormones produced by the anterior pituitary gland regulate an array of important physiological functions, but pituitary hormone disorders are not fully understood. Herein we report that genetically-engineered mice with deletion of the hedgehog signaling receptor Patched1 by S100a4 promoter-driven Cre recombinase (S100a4-Cre;Ptch1fl/fl mutants) exhibit adult-onset hypogonadotropic hypogonadism and multiple pituitary hormone disorders. During the transition from puberty to adult, S100a4-Cre;Ptch1fl/fl mice of both sexes develop hypogonadism coupled with reduced gonadotropin levels.

Meeting summary: the inaugural meeting of the US DOHaD society.

The US chapter of the International Developmental Origins of Health and Disease (DOHaD) Society recently held its inaugural meeting in Detroit, MI. US-based DOHaD researchers gathered both to create this new society chapter and share their latest research. The US DOHaD Society will provide a much-needed domestic forum for a broad range of DOHaD topics including nutrition, toxicology, stress, epidemiology, epigenetics, and more.

A plurality of molecular targets: The receptor ecosystem for bisphenol-A (BPA).

Bisphenol-A (BPA) is a well-known endocrine disrupting compound (EDC), capable of affecting the normal function and development of the reproductive system, brain, adipose tissue, and more. In spite of these diverse and well characterized effects, there is often comparatively little known about the molecular mechanisms which bring them about. BPA has traditionally been regarded as a primarily estrogenic EDC, and this perspective is often what guides research into the effects of BPA.

Measuring the "transfer of meaning" through members of equivalence classes merged via a class-specific reinforcement procedure.

Seven participants received conditional discrimination training that established the 12 conditional relations A1B1, A2B2, A3B3, A1C1, A2C2, A3C3, D1E1, D2E2, D3E3, D1F1, D2F2, and D3F3. The A stimuli were pictures of faces portraying emotional expressions; the others were arbitrary forms. Correct responses resulted in presentations of class-specific reinforcers, Sr1, Sr2, and Sr3.

Perinatal Exposure to Low-Dose Bisphenol-A Disrupts the Structural and Functional Development of the Hypothalamic Feeding Circuitry.

Bisphenol-A (BPA) is a component of polycarbonate and other plastics to which humans are regularly exposed at low levels. BPA is characterized as an endocrine disruptor because of observations of its estrogenic activity in various experimental models. We have previously shown evidence of disrupted hypothalamic feeding circuitry and leptin sensitivity in adult BPA-exposed animals subjected to a high-fat diet, but because these animals were already exhibiting a diet-induced obese phenotype, we could not rule out the possibility that these observations were simply consequences of the obesity, not a preexisting phenotype produced by BPA exposure.

POMC and NPY mRNA expression during development is increased in rat offspring brain from mothers fed with a high fat diet.

Developmental programing is influenced by perinatal nutrition and it has long-lasting impacts on adult metabolism in the offspring. In particular, maternal high fat diet has been associated with increased risk of obesity and metabolic disorders during adulthood in the descendants. These effects may be due to the effects of the high fat diet on the development of the systems that regulate food intake and energy balance in the offspring hypothalamus.

Triticale Bran Alkylresorcinols Enhance Resistance to Oxidative Stress in Mice Fed a High-Fat Diet.

Triticale (× Whitm.) is a cereal grain with high levels of alkyresorcinols (AR) concentrated in the bran. These phenolic lipids have been shown to reduce or inhibit triglyceride accumulation and protect against oxidation; however, their biological effects have yet to be evaluated .

Rats with a truncated ghrelin receptor (GHSR) do not respond to ghrelin, and show reduced intake of palatable, high-calorie food.

Ghrelin, a peptide hormone produced by the stomach, is the endogenous ligand for the Growth Hormone Secretagogue Receptor (GHSR). Ghrelin acts on the GHSR to increase food intake, appetitive behaviors, and adiposity. Recently, a rat model with a null mutation to the GHSR gene (FHH-GHSR(m1/Mcwi)) was generated and used in behavioral studies, but the basic metabolic phenotype of this strain as well as that of the background strain (Fawn Hooded Hypertensive, FHH) has not been characterized in detail.

Novel Regulator of Acylated Ghrelin, CF801, Reduces Weight Gain, Rebound Feeding after a Fast, and Adiposity in Mice.

Ghrelin is a 28 amino acid hormonal peptide that is intimately related to the regulation of food intake and body weight. Once secreted, ghrelin binds to the growth hormone secretagogue receptor-1a, the only known receptor for ghrelin and is capable of activating a number of signaling cascades, ultimately resulting in an increase in food intake and adiposity. Because ghrelin has been linked to overeating and the development of obesity, a number of pharmacological interventions have been generated in order to interfere with either the activation of ghrelin or interrupting ghrelin signaling as a means to reducing appetite and decrease weight gain.

Embryonic development of the hypothalamic feeding circuitry: Transcriptional, nutritional, and hormonal influences.

Background: Embryonic neurogenesis and differentiation in the hypothalamic feeding circuitry is under the control of a variety of diffused morphogens and intrinsic transcription factors, leading to the unique structural and functional characteristics of each nucleus.

Scope Of Review: The transcriptional regulation of the development of feeding neuroendocrine systems during the period of embryonic neurogenesis and differentiation will be reviewed here, with a special emphasis on genetic and environmental manipulations that yield an adverse metabolic phenotype.

Major Conclusions: Emerging data suggest that developmental mechanisms can be perturbed not only by genetic manipulation, but also by manipulations to maternal nutrition during the gestational period, leading to long-lasting behavioral, neurobiological, and metabolic consequences.

Rapid Teaching of Arbitrary Matching in Individuals with Intellectual Disabilities.

This research extended to arbitrary matching-to-sample procedures a method that was successful in rapidly establishing identity matching in children with and without intellectual disabilities (Mackay et al., 2002). The method involves increasing the number of identical comparison stimuli in a choice array in order to create a homogenous background that makes the target more salient, thus likely to prompt selection.

Rapid generation of balanced trial distributions for discrimination learning procedures: a technical note.

We describe novel computer algorithms for rapid, sometimes virtually instantaneous generation of trial sequences needed to instrument many behavioral research procedures. Implemented on typical desktop or laptop computers, the algorithms impose constraints to forestall development of undesired stimulus control by position, recent trial outcomes, and other variables that could impede simple and conditional discrimination learning. They yield trial-by-trial lists of sequences that can serve (1) as inputs to procedure control software or (2) in generating templates for constructing sessions for implementation by hand or machine.

Rats perinatally exposed to food restriction and high-fat diet show differences in adipose tissue gene expression under chronic caloric restriction.

The aim of this study is to analyze how maternal diet during the lactational period influences the adipose tissue response to chronic caloric restriction in offspring. Lactating dams were subjected to one of three treatments: 50% food restriction (FR), ad lib standard chow (AL), or ad lib high-fat diet (HF). Juveniles were first weaned onto standard chow, then in adulthood 50% calorically restricted and maintained at 90% of normal body weight for 60 d.

Organizational effects of perinatal exposure to bisphenol-A and diethylstilbestrol on arcuate nucleus circuitry controlling food intake and energy expenditure in male and female CD-1 mice.

The endocrine disrupting compound bisphenol-A (BPA) has been reported to act as an obesogen in rodents exposed perinatally. In this study, we investigated the effects of early-life BPA exposure on adult metabolic phenotype and hypothalamic energy balance circuitry. Pregnant and lactating CD-1 dams were exposed, via specially prepared diets, to 2 environmentally relevant doses of BPA.

Stimulus equivalence, generalization, and contextual stimulus control in verbal classes.

Stimulus generalization and contextual control affect the development of equivalence classes. Experiment 1 demonstrated primary stimulus generalization from the members of trained equivalence classes. Adults were taught to match six spoken Icelandic nouns and corresponding printed words and pictures to one another in computerized three-choice matching-to-sample tasks.