In animal communication, functionally referential alarm calls elicit the same behavioral responses as their referents, despite their typically distinct bioacoustic traits. Yet the auditory forebrain ...in at least one songbird species, the black-capped chickadee Poecile atricapillus, responds similarly to threat calls and their referent predatory owl calls, as assessed by immediate early gene responses in the secondary auditory forebrain nuclei. Whether and where in the brain such perceptual and cognitive equivalence is processed remains to be understood in most other avian systems. Here, we studied the functional neurogenomic (non-) equivalence of acoustic threat stimuli perception by the red-winged blackbird Agelaius phoeniceus in response to the actual calls of the obligate brood parasitic brown-headed cowbird Molothrus ater and the referential anti-parasitic alarm calls of the yellow warbler Setophaga petechia, upon which the blackbird is known to eavesdrop. Using RNA-sequencing from neural tissue in the auditory lobule (primary and secondary auditory nuclei combined), in contrast to previous findings, we found significant differences in the gene expression profiles of both an immediate early gene, ZENK (egr-1), and other song-system relevant gene-products in blackbirds responding to cowbird vs. warbler calls. In turn, direct cues of threats (including conspecific intruder calls and nest-predator calls) elicited higher ZENK and other differential gene expression patterns compared to harmless heterospecific calls. These patterns are consistent with a perceptual non-equivalence in the auditory forebrain of adult male red-winged blackbirds in response to referential calls and the calls of their referents.
•Early exposure to salient cues can critically shape the development of social behaviors.•Different acoustic playbacks in ovo alter genome-wide methylation of the auditory forebrain in late-stage ...zebra finch embryos.•Immediate early gene activation is negatively correlated to relative global methylation in the same sample of individuals.•The data support a methylation-mediated embryonic acoustic programming hypothesis for songbird social and communicative behavioral development.
Early exposure to salient cues can critically shape the development of social behaviors. For example, both oscine birds and humans can hear and learn to recognize familiar sounds in ovo and in utero and recognize them following hatching and birth, respectively. Here we demonstrate that different chronic acoustic playbacks alter genome-wide methylation of the auditory forebrain in late-stage zebra finch (Taeniopygia guttata) embryos. Within the same subjects, immediate early gene activation in response to acute con- or heterospecific song exposure is negatively correlated with methylation extent in response to repeated daily prior exposure to the same type of stimuli. Specifically, we report less relative global methylation following playbacks of conspecific songs and more methylation following playbacks of distantly-related heterospecific songs. These findings offer a neuroepigenomic mechanism for the ontogenetic impacts of early acoustic experiences in songbirds.
Generalist obligate brood parasites are excellent models for studies of developmental plasticity, as they experience a range of social and environmental variation when raised by one of their many ...hosts. Parasitic Brown-headed Cowbirds (Molothrus ater (Boddaert, 1783)) exhibit host-specific growth rates, yet Cowbird growth rates are not predicted by hosts’ incubation or brooding periods. We tested the novel “growth-tuning” hypothesis which predicts that total asynchrony between Cowbirds’ and hosts’ nesting periods results in faster parasitic growth in nests where host young fledge earlier than Cowbirds. We tested this prediction using previously published and newly added nestling mass data across diverse host species. Total nesting period asynchrony (summed across incubation and brooding stages) predicted Cowbird growth; 8-day-old Cowbirds were heavier in host nests with relatively shorter nesting periods. We further explored the drivers of variation in growth using mass measurements of Cowbirds in Song Sparrow (Melospiza melodia (A. Wilson, 1810)) and Red-winged Blackbird (Agelaius phoeniceus (Linnaeus, 1766)) nests. Our top models included host species (Cowbirds grew faster in Sparrow nests), numbers of nestmates (slowest when raised alone), and sex (males grew faster). These results confirm that multiple social and environmental factors predict directional patterns of developmental plasticity in avian generalist brood parasites.
The purpose of this study was to determine the effectiveness of an amino acid-based infant formula in infants with continued symptoms suggestive of formula protein intolerance while they were ...receiving casein hydrolysate formula (CHF). Twenty-eight infants, 22 to 173 days of age, were enrolled; each had received CHF for an average of 40 days (10 to 173 days) and continued to have bloody stools, vomiting, diarrhea, irritability, or failure to gain weight, or a combination of these symptoms. Sigmoidoscopy with rectal biopsy was performed in all infants. The infants then received an amino acid-based infant formula, Neocate, for 2 weeks. After 2 weeks of treatment, 25 of the infants demonstrated resolution of their symptoms and underwent challenge with CHF. Of the 25 who were challenged, eight tolerated the CHF and the remainder had recurrence of their symptoms. The histologic features in these infants varied from eosinophilic infiltration to normal. We conclude that not all infants with apparent formula protein-induced colitis respond to CHF and that these infants may have resolution of their symptoms when fed an amino acid-based infant formula.
Brood (social) parasites and their hosts exhibit a wide range of adaptations and counter-adaptations as part of their ongoing coevolutionary arms races. Obligate avian brood parasites are expected to ...use potential host species with more easily accessible nests, while potential hosts are expected to evade parasitism by building more concealed nests that are difficult for parasites to enter and in which to lay eggs. We used phylogenetically informed comparative analyses, a global database of the world's brood parasites, their host species, and the design of avian host and non-host nests (approx. 6200 bird species) to examine first, whether parasites preferentially target host species that build open nests and, second, whether host species that build enclosed nests are more likely to be targeted by specialist parasites. We found that species building more accessible nests are more likely to serve as hosts, while host species with some of the more inaccessible nests are targeted by more specialist brood parasites. Furthermore, evolutionary-transition analyses demonstrate that host species building enclosed nests frequently evolve to become non-hosts. We conclude that nest architecture and the accessibility of nests for parasitism represent a critical stage of the ongoing coevolutionary arms race between avian brood parasites and their hosts.
The role of species interactions, as well as genetic and environmental factors, all likely contribute to the composition and structure of the gut microbiome; however, disentangling these independent ...factors under field conditions represents a challenge for a functional understanding of gut microbial ecology. Avian brood parasites provide unique opportunities to investigate these questions, as brood parasitism results in parasite and host nestlings being raised in the same nest, by the same parents. Here we utilized obligate brood parasite brown‐headed cowbird nestlings (BHCO; Molothrus ater) raised by several different host passerine species to better understand, via 16S rRNA sequencing, the microbial ecology of brood parasitism. First, we compared faecal microbial communities of prothonotary warbler nestlings (PROW; Protonotaria citrea) that were either parasitized or non‐parasitized by BHCO and communities among BHCO nestlings from PROW nests. We found that parasitism by BHCO significantly altered both the community membership and community structure of the PROW nestling microbiota, perhaps due to the stressful nest environment generated by brood parasitism. In a second dataset, we compared faecal microbiotas from BHCO nestlings raised by six different host passerine species. Here, we found that the microbiota of BHCO nestlings was significantly influenced by the parental host species and the presence of an inter‐specific nestmate. Thus, early rearing environment is important in determining the microbiota of brood parasite nestlings and their companion nestlings. Future work may aim to understand the functional effects of this microbiota variability on nestling performance and fitness.
•A mouse model of influenza A virus (IAV) infection during pregnancy was established.•Maternal IAV infection caused mild pathology in the placenta without pup loss.•Moderate gestational IAV infection ...did not induce fetal brain inflammation.•Enhanced maternal IL-17A was not observed within the intestine nor in circulation.•An IAV infection severity threshold may exist for inducing fetal neuroinflammation.
Maternal infection during pregnancy is a known risk factor for offspring mental health disorders. Animal models of maternal immune activation (MIA) have implicated specific cellular and molecular etiologies of psychiatric illness, but most rely on pathogen mimetics. Here, we developed a mouse model of live H3N2 influenza A virus (IAV) infection during pregnancy that induces a robust inflammatory response but is sublethal to both dams and offspring. We observed classic indicators of lung inflammation and severely diminished weight gain in IAV-infected dams. This was accompanied by immune cell infiltration in the placenta and partial breakdown of placental integrity. However, indications of fetal neuroinflammation were absent. Further hallmarks of mimetic-induced MIA, including enhanced circulating maternal IL-17A, were also absent. Respiratory IAV infection did result in an upregulation in intestinal expression of transcription factor RORγt, master regulator of a subset of T lymphocytes, TH17 cells, which are heavily implicated in MIA-induced etiologies. Nonetheless, subsequent augmentation in IL-17A production and concomitant overt intestinal injury was not evident. Our results suggest that mild or moderately pathogenic IAV infection during pregnancy does not inflame the developing fetal brain, and highlight the importance of live pathogen infection models for the study of MIA.
Cholesterol loaded macrophage foam cells are a prominent feature of atherosclerotic plaques. Single-cell RNA sequencing has identified foam cells as TREM2 (triggering receptor expressed on myeloid ...cells 2) positive populations with low expression of inflammatory genes, resembling the TREM2 positive microglia of neurodegenerative diseases. Cholesterol loading of macrophages in vitro results in activation of LXR (liver X receptor) transcription factors and suppression of inflammatory genes.
To test the hypothesis that LXRs mediate anti-inflammatory effects in
expressing atherosclerotic plaque foam cells, we performed RNA profiling on plaque cells from hypercholesterolemic mice with myeloid LXR deficiency.
Myeloid LXR deficiency led to a dramatic increase in atherosclerosis with increased monocyte entry, foam cell formation, and plaque inflammation. Bulk cell-RNA profiling of plaque myeloid cells showed prominent upregulation of inflammatory mediators including oxidative, chemokine, and chemotactic genes. Single-cell RNA sequencing revealed increased numbers of foamy TREM2-expressing macrophages; however, these cells had reduced expression of the
gene expression module, including phagocytic and cholesterol efflux genes, and had switched to a proinflammatory and proliferative phenotype. Expression of
was suppressed by inflammatory signals but not directly affected by LXR activation in bone marrow-derived macrophages.
Our current studies reveal the key role of macrophage LXRs in promoting the
gene expression program and in suppressing inflammation in foam cells of atherosclerotic plaques.
The aim of this study was to determine whether the type of feeding during the first 4 months of life affects bone mineral density at 4 years of age.
Healthy 4-year-old children were recruited from ...the offices of primary health care providers. After confirming the type of infant feeding by history, dual energy x-ray absorptiometry analysis was obtained at the University of Nebraska Medical Center and evaluated by a radiologist blinded as to feeding type.
One hundred and seventy-eight children completed the study (58% male, 85% Caucasian; mean age, 4.5 years). All children had exclusively consumed human milk (n = 57), an infant formula containing no palm olein oil (n = 56) or an infant formula containing palm olein oil (n = 65) during the first 4 months of life. At 4 years of age, no significant differences were noted in bone mineral content or bone mineral density (P = 0.51 and 0.89, respectively) among the three feeding groups as measured by dual energy x-ray absorptiometry. Total body bone mineral content and bone mineral density varied by gender, with males having significantly higher values than females regardless of feeding type (P = 0.028 and P < 0.001, respectively).
There is no association between the use of palm olein formula during the first 4 months of life and subsequent bone mineral content and bone mineral density in healthy 4-year-old children.
This investigation examines the absolute quantities and relative proportions of dietary medium-chain triglyceride and long-chain triglyceride needed to prevent essential fatty deficiency and maximize ...absorption of dietary energy in infants with chronic liver disease