Transkingdom control of microbiota diurnal oscillations promotes metabolic homeostasis.

All domains of life feature diverse molecular clock machineries that synchronize physiological processes to diurnal environmental fluctuations. However, no mechanisms are known to cross-regulate prokaryotic and eukaryotic circadian rhythms in multikingdom ecosystems. Here, we show that the intestinal microbiota, in both mice and humans, exhibits diurnal oscillations that are influenced by feeding rhythms, leading to time-specific compositional and functional profiles over the course of a day. Ablation of host molecular clock components or induction of jet lag leads to aberrant microbiota diurnal fluctuations and dysbiosis, driven by impaired feeding rhythmicity. Consequently, jet-lag-induced dysbiosis in both mice and humans promotes glucose intolerance and obesity that are transferrable to germ-free mice upon fecal transplantation. Together, these findings provide evidence of coordinated metaorganism diurnal rhythmicity and offer a microbiome-dependent mechanism for common metabolic disturbances in humans with aberrant circadian rhythms, such as those documented in shift workers and frequent flyers.

The ion channel TRPV1 regulates the activation and proinflammatory properties of CD4⁺ T cells.

TRPV1 is a Ca(2+)-permeable channel studied mostly as a pain receptor in sensory neurons. However, its role in other cell types is poorly understood. Here we found that TRPV1 was functionally expressed in CD4(+) T cells, where it acted as a non-store-operated Ca(2+) channel and contributed to T cell antigen receptor (TCR)-induced Ca(2+) influx, TCR signaling and T cell activation. In models of T cell-mediated colitis, TRPV1 promoted colitogenic T cell responses and intestinal inflammation. Furthermore, genetic and pharmacological inhibition of TRPV1 in human CD4(+) T cells recapitulated the phenotype of mouse Trpv1(-/-) CD4(+) T cells. Our findings suggest that inhibition of TRPV1 could represent a new therapeutic strategy for restraining proinflammatory T cell responses.

The effects of parental presence on amygdala and mPFC activation during fear conditioning: An exploratory study.

Learning safe versus dangerous cues is crucial for survival. During development, parents can influence fear learning by buffering their children's stress response and increasing exploration of potentially aversive stimuli. Rodent findings suggest that these behavioral effects are mediated through parental presence modulation of the amygdala and medial prefrontal cortex (mPFC). Here, we investigated whether similar parental modulation of amygdala and mPFC during fear learning occurs in humans. Using a within-subjects design, behavioral (final N = 48, 6-17 years, mean = 11.61, SD = 2.84, 60% females/40% males) and neuroimaging data (final N = 39, 6-17 years, mean = 12.03, SD = 2.98, 59% females/41% males) were acquired during a classical fear conditioning task, which included a CS+ followed by an aversive noise (US; 75% reinforcement rate) and a CS-. Conditioning occurred once in physical contact with the participant's parent and once alone (order counterbalanced). Region of interest analyses examined the unconditioned stress response by BOLD activation to the US (vs. implicit baseline) and learning by activation to the CS+ (vs. CS-). Results showed that during US presentation, parental presence reduced the centromedial amygdala activity, suggesting buffering of the unconditioned stress response. In response to learned stimuli, parental presence reduced mPFC activity to the CS+ (relative to the CS-), although this result did not survive multiple comparisons' correction. These preliminary findings indicate that parents modulate amygdala and mPFC activity during exposure to unconditioned and conditioned fear stimuli, potentially providing insight into the neural mechanisms by which parents act as a social buffer during fear learning. RESEARCH HIGHLIGHTS: (1)This study used a within-participant experimental design to investigate how parental presence (vs. absence) affects youth's neural responses in a classical fear conditioning task. (2)Parental presence reduced the youth's centromedial amygdala activation to the unconditioned stimulus (US), suggesting parental buffering of the neural unconditioned response (UR). (3)Parental presence reduced the youth's mPFC activation to a conditioned threat cue (CS+) compared to a safety cue (CS-), suggesting possible parental modulation of fear learning.

Personal values and sustained attention as predictors of children's helping behavior in middle childhood.

OBJECTIVE: This study tested the effect of personal values (motivation) and sustained attention (cognitive ability) on children's helping behavior. METHOD: Children (N = 162, age range 8-9 years, mean = 8.81, SD = 0.43) completed value ranking and go/no-go tasks, and their helping behavior was examined. RESULTS: Children who valued self-transcendence over self-enhancement helped more than others. Surprisingly, children's lack of sustained attention was associated with more helping among those who valued self-transcendence over self-enhancement or openness-to-change over conservation values. Valuing both self-transcendence and openness-to-change was also associated with more helping. CONCLUSIONS: Children are more likely to help others if they value self-transcendence and openness to change. Notably, children's tendency to act upon these values may be facilitated (rather than obstructed by) low attention skills.

The empathic personality profile: Using personality characteristics to reveal genetic, environmental, and developmental patterns of adolescents' empathy.

OBJECTIVE: How do genetic and environmental processes affect empathy during early adolescence? This study illuminated this question by examining the aetiology of empathy with the aetiology of other personality characteristics. METHOD: Israeli twin adolescents rated their empathy and personality at ages 11 (N = 1176) and 13 (N = 821) (733 families, 51.4% females). Parents rated adolescents' emotional empathy. Adolescents performed an emotion recognition task, indicating cognitive empathy. RESULTS: Using a cross-validated statistical learning algorithm, this study found emotional and cognitive "empathic personality profiles," which describe and predict self-reported empathy from nuanced Big-Five personality characteristics, or "nuances" (i.e., individual items). These profiles predicted empathy moderately (R2  = 0.17-0.24) and were stable and robust, within each age and between ages. They also predicted empathy in a new sample of older nontwin adolescents (N = 96) and were validated against non-self-report empathy measures. Both emotional and cognitive empathy were predicted by nuances representing positive attitudes toward others, trust, forgiveness, and openness to experiences. Emotional empathy was also predicted by nuances representing anxiousness and negative reactivity. Twin analyses revealed overlapping genetic and environmental influences on empathy and the empathic personality profiles and overlapping environmental influences on empathy-personality change. CONCLUSIONS: This study demonstrates how addressing the complexity of individuals' personalities can inform adolescents' empathy development.

Changing genetic architecture of body mass index from infancy to early adulthood: an individual based pooled analysis of 25 twin cohorts.

BACKGROUND: Body mass index (BMI) shows strong continuity over childhood and adolescence and high childhood BMI is the strongest predictor of adult obesity. Genetic factors strongly contribute to this continuity, but it is still poorly known how their contribution changes over childhood and adolescence. Thus, we used the genetic twin design to estimate the genetic correlations of BMI from infancy to adulthood and compared them to the genetic correlations of height. METHODS: We pooled individual level data from 25 longitudinal twin cohorts including 38,530 complete twin pairs and having 283,766 longitudinal height and weight measures. The data were analyzed using Cholesky decomposition offering genetic and environmental correlations of BMI and height between all age combinations from 1 to 19 years of age. RESULTS: The genetic correlations of BMI and height were stronger than the trait correlations. For BMI, we found that genetic correlations decreased as the age between the assessments increased, a trend that was especially visible from early to middle childhood. In contrast, for height, the genetic correlations were strong between all ages. Age-to-age correlations between environmental factors shared by co-twins were found for BMI in early childhood but disappeared altogether by middle childhood. For height, shared environmental correlations persisted from infancy to adulthood. CONCLUSIONS: Our results suggest that the genes affecting BMI change over childhood and adolescence leading to decreasing age-to-age genetic correlations. This change is especially visible from early to middle childhood indicating that new genetic factors start to affect BMI in middle childhood. Identifying mediating pathways of these genetic factors can open possibilities for interventions, especially for those children with high genetic predisposition to adult obesity.

Same Day Infusion of Iron Therapy Is Associated With No Increased Risk for Adverse Events Among Patients Receiving Biological Infusions for Inflammatory Bowel Disease.

GOALS: The goal of this study was to compare the relative safety of administering iron infusions on the same day as intravenous (IV) biological therapy to the administration of these treatments on different days in patients with inflammatory bowel disease (IBD). BACKGROUND: IV iron therapy is often required in patients with IBD. Many patients with IBD who receive IV iron therapy in the outpatient setting also receive biological infusion therapy for treatment of their IBD. STUDY: Patients with IBD who received IV iron therapy at a single infusion center were included. We compared documented infusion-related reactions in patients with patients receiving an iron infusion on the same day as their biological infusion to those who received their iron infusion on a different day. RESULTS: Among 481 patients, 129 received an iron infusion on the same day as a biologic infusion. There was no significant difference in the incidence of infusion reaction when comparing patients who received biological infusion therapy in the same session as the iron infusion to those patients who received a biological infusion on a different day (5% vs. 7%, P =0.246) or any IBD-related therapy (5% vs. 8%, P =0.206). CONCLUSIONS: The frequency and type of infusion reactions in patients receiving IV iron therapy on the same day after IV therapy with biologics was not increased compared with patients who received a biological infusion on a different day. A sequential infusion of biological therapy followed by IV iron therapy may be a safe and cost-effective approach.

Association of eosinophilic esophagitis with autoimmune and connective tissue disorders, and the impact on treatment response.

Eosinophilic esophagitis (EoE) has been associated with autoimmune (AI) and connective tissue disorders (CTDs), but clinical correlates and treatment response to topical corticosteroids (tCS) for patients with both conditions are not well known. We aimed to determine the prevalence and clinical features of AI/CTDs in EoE patients, and assess the response to tCS. In this retrospective cohort study of adults and children newly diagnosed with EoE in the University of North Carolina EoE Clinicopathologic database, we extracted clinical characteristics and treatment response data. We compared EoE patients with and without AI/CTDs, identified independently associated factors, and explored treatment responses. Of 1029 EoE patients, 61 (5.9%) had an AI/CTDs. The most common AI/CTDs were psoriasis/psoriatic arthritis (P/PA) (1.7%), Hashimoto's (1.2%), and rheumatoid arthritis (RA) (1%). Compared to those without AI/CTDs, AI/CTDs patients were older (35 vs. 28 years, P = 0.004), more likely to be female (51% vs. 30%, P = 0.001), have insurance (93% vs. 78%, P = 0.004) and a longer symptom duration prior to EoE diagnosis (10 vs. 7 years, P = 0.02). Older age, female sex, having insurance, and having allergic rhinitis were independently associated with AI/CTDs. AI/CTD patients with EoE were less likely to have a symptom response (47% vs. 79%, P = 0.003). Overlap between EoE and AI/CTDs was uncommon, seen in approximately 6%, with P/PA, Hashimoto's, and RA being most frequent. In conclusion, older age, female sex, having insurance, and allergic rhinitis were independently associated with AI/CTDs. EoE patients with AI/CTDs had less symptom response, with trendtowards lower endoscopic and histologic responses, to tCS therapy.

Musicality was not selected for, rather humans have a good reason to learn music.

We propose that not social bonding, but rather a different mechanism underlies the development of musicality: being unable to survive alone. The evolutionary constraint of being dependent on other humans for survival provides the ultimate driving force for acquiring human faculties such as sociality and musicality, through mechanisms of learning and neural plasticity. This evolutionary mechanism maximizes adaptation to a dynamic environment.

From negative reactivity to empathic responding: Infants high in negative reactivity express more empathy later in development, with the help of regulation.

Empathy has great effect on human well-being, promoting healthy relationships and social competence. Although it is increasingly acknowledged that infants show empathy toward others, individual differences in infants' empathy from the first year of life have rarely been investigated longitudinally. Here we examined how negative reactivity and regulation, two temperament traits that predict empathic responses in older children and adults, relate to infants' empathy. Infants were studied at the ages of nine (N = 275) and 18 (N = 301) months (194 infants were studied at both ages). Empathic responses were assessed by infants' observed reactions to an experimenter's simulated distress. Negative reactivity (fear, sadness, and distress to limitations) and regulation (soothability and effortful control) were assessed by parental reports. Negative reactivity was also examined by infants' observed reactions to an adult stranger (fear) and during interaction with their mothers (displays of sadness/distress). When examined cross-sectionally, infants' fear and distress to limitations associated with self-distress in response to others' distress. In contrast, when examined longitudinally, early sadness and distress to limitations, but not fear, associated with later empathic concern and inquisitiveness. Moreover, this longitudinal relation was moderated by infants' soothability and was evident only for children that had high soothability by the later time-point. Our findings suggest that infants who at an earlier age show negative reactivity, react later in development with more empathy if they achieve sufficient regulation abilities. By that, the findings stress the developmental nature of temperament-empathy relations during infancy.

The Longitudinal Israeli Study of Twins (LIST) Reaches Adolescence: Genetic and Environmental Pathways to Social, Personality and Moral Development.

The Longitudinal Israeli Study of Twins (LIST) focuses on the developmental, genetic and environmental contributions to individual differences in children's and adolescents' social behavior. Key variables have been empathy, prosocial behavior, temperament and values. Another major goal of LIST has been to study gene-environment correlations, mainly concerning parenting. LIST includes 1657 families of Hebrew-speaking Israeli twins who have participated at least once in the study. Children's environment and their development are assessed in a multivariate, multimethod fashion, including observed, parent-reported and self-reported data. The current article summarizes and updates recent findings from LIST. For example, LIST provided evidence for the heritability of human values with the youngest sample to date, and the first genetic investigation of adolescents' identity formation. Finally, future aims of LIST are discussed.

The role of personal values in children's costly sharing and non-costly giving.

This study examined whether children's values, global and abstract motivations serving as guiding principles, are organized similarly to those of adults, whether values can predict individual differences in children's sharing behaviors, and whether the normative nature of the situation influences the expression of these individual differences. Children (N=243, ages 5-12years) participated in a values ranking task as part of a visit to a science museum. The majority of children (n=150) also participated in a task examining costly sharing (i.e., sharing that results in giving up part of one's own resources) and non-costly giving (i.e., giving that does not influence one's own share). Starting from 5years of age, children showed a structure of values similar to that of adolescents and adults, specifically contrasting preferences for opposing values (i.e., self-transcendence with self-enhancement and openness to change with conservation). Importance given to self-transcendence values related positively to costly sharing but not to non-costly giving, indicating that in situations where it is more normative to share, individual differences in values are less expressed in children's actual sharing. In addition, children's sex and age moderated the relation between values and behavior. Children's values are an important aspect of their developing personalities. Taking them into consideration can greatly promote the research of prosocial and normative development as well as our understanding of individual differences in children's behavior.

Twin's Birth-Order Differences in Height and Body Mass Index From Birth to Old Age: A Pooled Study of 26 Twin Cohorts Participating in the CODATwins Project.

We analyzed birth order differences in means and variances of height and body mass index (BMI) in monozygotic (MZ) and dizygotic (DZ) twins from infancy to old age. The data were derived from the international CODATwins database. The total number of height and BMI measures from 0.5 to 79.5 years of age was 397,466. As expected, first-born twins had greater birth weight than second-born twins. With respect to height, first-born twins were slightly taller than second-born twins in childhood. After adjusting the results for birth weight, the birth order differences decreased and were no longer statistically significant. First-born twins had greater BMI than the second-born twins over childhood and adolescence. After adjusting the results for birth weight, birth order was still associated with BMI until 12 years of age. No interaction effect between birth order and zygosity was found. Only limited evidence was found that birth order influenced variances of height or BMI. The results were similar among boys and girls and also in MZ and DZ twins. Overall, the differences in height and BMI between first- and second-born twins were modest even in early childhood, while adjustment for birth weight reduced the birth order differences but did not remove them for BMI.

The relationship between empathy and executive functions among young adolescents.

Empathy and executive functions (EFs) are multimodal constructs that enable individuals to cope with their environment. Both abilities develop throughout childhood and are known to contribute to social behavior and academic performance in young adolescents. Notably, mentalizing and EF activate shared frontotemporal brain areas, which in previous studies of adults led researchers to suggest that at least some aspects of empathy depend on intact EF mechanisms. Despite the substantial development that empathy and EF undergo during adolescence, no study to date has systematically examined the associations between components of empathy and EF in this age group. Here, we explore these associations using data from an online battery of tasks, collected as part of a longitudinal twin study (N = 593; Mage 11.09 ± 0.2; 53.46% female, Israeli adolescents from Jewish decent). Using a confirmatory factor analysis, we quantified the associations between the main components of empathy (mentalizing and interpersonal concern) and of EF (working memory [WM], inhibition and shifting [IaS]). We found that WM was related to both mentalizing and interpersonal concern, whereas IaS were related to mentalizing but not to interpersonal concern. We also discuss the genetic and environmental contributions to individual differences in each factor. Our findings show both similarities and differences from previous findings in adults, suggesting that the ongoing brain maturation processes and environmental age-dependent experiences in adolescence may affect the developing relation between cognitive and emotional development. These results have implications for better understanding and treating clinical populations demonstrating executive or emotional deficits, specifically during adolescence. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Food-specific IgA levels in esophageal biopsies are not sufficiently high to predict food triggers in eosinophilic esophagitis.

BACKGROUND: Eosinophilic esophagitis (EoE) is an immune-mediated disease, characterized by Th2-type inflammation linked to specific foods. No currently available allergy tests reliably identify food triggers in EoE, leading to empiric dietary elimination strategies. Recently, milk- and wheat-specific IgA in esophageal brushings were linked to clinical food triggers. In this study, we aimed to determine whether food-specific IgA from esophageal biopsies is associated with known food triggers. METHODS: A prior cohort of 21 patients (median age 39 years) with confirmed EoE underwent empirical elimination diets and subsequent reintroduction of foods to determine triggers. Archived baseline biopsies were used to quantify levels of peanut-, milk-, soy-, egg-, wheat-specific and total IgA by enzyme-linked immunosorbent assay. RESULTS: Overall, 13 patients (62%) responded to the dietary elimination as determined by histology (<15 eos/hpf), with milk and egg being the most common triggers. Biopsies had varying amounts of total IgA, while food-specific IgA was only detectable in 48 of 105 (46%) samples. Food-specific IgA was normalized to total IgA for each sample and stratified by whether a food was a known trigger. For all foods tested, there were no significant differences in IgA between positive and negative triggers. CONCLUSIONS: Food-specific IgA in esophageal biopsies was not associated with previously identified food triggers in this cohort. Future studies comparing food-specific IgA in esophageal brushings, mucous scrapings, and biopsies from patients with known triggers will be critical to determining whether food-specific IgA may serve as a biomarker for identification of EoE triggers.

Older patients with eosinophilic esophagitis have high treatment response to topical steroids.

BACKGROUND: There are few data assessing treatment response in older eosinophilic esophagitis (EoE) patients and we evaluated treatment outcomes to topical corticosteroids (tCS) in this older population. METHODS: This retrospective cohort study of the UNC EoE Clinicopathologic database included subjects with a new diagnosis of EoE treated with tCS. Histologic responses, global symptom response, and endoscopic changes were recorded. Older EoE patients (≥65 years) were compared to younger EoE patients (<65). RESULTS: We identified 467 EoE patients treated with tCS, 12 (3%) of whom were ≥65 years. Compared to those <65 years, patients ≥65 had longer symptom duration and worse endoscopy scores, but most clinical features were similar. Post-treatment peak eosinophil counts trended higher in the <65 group (25.0 vs 5.5; p = 0.07). Histological response was greater in the ≥65 population at <15 eos/hpf (92% vs 57%; p = 0.02), ≤6 eos/hpf (83% vs 50%; p = 0.02), and <1 eos/hpf (58% vs 29%; p = 0.03). Older age was independently associated with increased odds of histologic response (adjusted OR 8.48, 95% CI: 1.08-66.4). CONCLUSIONS: EoE patients ≥65 years had a higher likelihood of responding to tCS therapy, suggesting they should be studied more closely and included in future trials.

Social interaction context shapes emotion recognition through body language, not facial expressions.

The social context-seeing people emotionally interacting-is one of the most common contexts in which emotion perception occurs. Despite its importance, emotion perception of social interactions from a 3rd-person perspective is poorly understood. Here we investigated whether emotion recognition of fear and anger is facilitated by mere congruency (the contextual figure exhibits the same emotion as the target) or by functional relations (the contextual figure exhibits a complementary emotion to the target). Furthermore, we examined which expression channel, face or body, drives social context effects. In the 1st 2 experiments (Studies 1a and 1b), participants in an online survey platform (N = 146) or university students (N = 34), viewed interacting figures displaying fear or anger, presented either as faces, bodies, or both. Participants were instructed to categorize the target figure's emotions while the other figure served as context. Results showed that fear recognition was facilitated by an interacting angry figure more strongly than by an interacting fearful figure. Moreover, this effect occurred when participants viewed the figures' bodies (with or without the faces), but not when they viewed the figures' faces alone. A 3rd online experiment (Study 2) established that this context effect was stronger when participants (N = 464) watched the figures interacting (facing each other) than when figures were not interacting (facing away from each other), suggesting that social context influences emotion perception by revealing the interactants' relation. Our findings demonstrate that emotional perception is grounded in the broader process of social interaction and highlight the role of the body in interpersonal context effects. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

The genetic and environmental origins of emotional and cognitive empathy: Review and meta-analyses of twin studies.

Empathy is considered a cornerstone of human social experience, and as such has been widely investigated from psychological and neuroscientific approaches. To better understand the factors influencing individual differences in empathy, we reviewed and meta-analyzed the behavioral genetic literature of emotional empathy- sharing others' emotions (k=13), and cognitive empathy- understanding others' emotions (k = 15), as manifested in twin studies. Results showed that emotional empathy is more heritable, 48.3 % [41.3 %-50.6 %], than cognitive empathy, 26.9 % [18.1 %-35.8 %]. Moreover, cognitive empathy as examined by performance tests was affected by the environment shared by family members, 11.9 % [2.6 %-21.0 %], suggesting that emotional understanding is influenced, to some degree, by environmental factors that have similar effects on family members beyond their genetic relatedness. The effects of participants' age and the method used to asses empathy on the etiology of empathy were also examined. These findings have implications for understanding how individual differences in empathy are formed. After discussing these implications, we suggest theoretical and methodological future research directions that could potentially elucidate the relations between genes, brain, and empathy.

Genetic and environmental influences on human height from infancy through adulthood at different levels of parental education.

Genetic factors explain a major proportion of human height variation, but differences in mean stature have also been found between socio-economic categories suggesting a possible effect of environment. By utilizing a classical twin design which allows decomposing the variation of height into genetic and environmental components, we tested the hypothesis that environmental variation in height is greater in offspring of lower educated parents. Twin data from 29 cohorts including 65,978 complete twin pairs with information on height at ages 1 to 69 years and on parental education were pooled allowing the analyses at different ages and in three geographic-cultural regions (Europe, North America and Australia, and East Asia). Parental education mostly showed a positive association with offspring height, with significant associations in mid-childhood and from adolescence onwards. In variance decomposition modeling, the genetic and environmental variance components of height did not show a consistent relation to parental education. A random-effects meta-regression analysis of the aggregate-level data showed a trend towards greater shared environmental variation of height in low parental education families. In conclusion, in our very large dataset from twin cohorts around the globe, these results provide only weak evidence for the study hypothesis.

A longitudinal genetically informed analysis of parental negativity and children's negative emotionality in middle childhood.

Children's negative emotionality (NE) is frequently associated with parental negativity, but causal understanding of this relationship is limited. In addition, little is known about how genetic and environmental factors affect this relationship during middle childhood. We addressed these gaps by applying a quantitative genetic analysis to cross-lagged associations between mothers' and fathers' parental negativity and children's NE during middle childhood. The sample comprised of 456 families when the children were 6.5 years old, and 401 families when the children were 8/9 years old. Mothers' and fathers' negativity and children's NE were assessed using questionnaires. Results showed that variation in parental negativity was mainly accounted for by the environment shared by children, with some indication of an evocative effect of the children's genes on mothers, but not fathers. Children's NE was accounted for by both genetic and shared environmental influences. Parental negativity and children's NE had moderate continuity over the course of two years. Mothers' (but not fathers') negativity when the children were 6.5 years old predicted change in children's NE (rated by the same or the other parent) toward age 8/9 years, but not the other way around. Shared environmental influences were the main contributor to the association between earlier mothers' negativity and later children's NE. Thus, although children's NE was partially heritable, and parenting too was partially accounted for by children's genes, the association between parental negativity and children's NE, at this age, reflects environmental effects and is compatible with mothers' influence on children. (PsycINFO Database Record (c) 2019 APA, all rights reserved).