The Early Life Microbiota Mediates Maternal Effects on Offspring Growth in a Nonhuman Primate
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Mammalian mothers influence offspring development by providing nutrients and other bioactive compounds through the placenta or milk. A relatively unexplored mechanism for maternal effects is vertical transmission of bacteria through milk to the infant gut. Infants that receive more glycan-utilizing bacteria from milk might better exploit oligosaccharides, which could improve nutrition and accelerate growth.
Heritability of Social Behavioral Phenotypes and Preliminary Associations with Autism Spectrum Disorder Risk Genes in Rhesus Macaques: A Whole Exome Sequencing Study
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Investigators quantified individual variation in social interactions among juvenile rhesus macaques of both sexes using both a standard macaque ethogram (a catalogue of animal behavior over time) and a macaque-relevant modification of the human Social Responsiveness Scale to study genetic influences on key aspects of social behavior and interactions. The analyses demonstrate that various aspects of juvenile social behavior exhibit significant genetic heritability, with quantitative genetic effects similar to autism spectrum disorder (ASD) in human children.
Reduced Infant Rhesus Macaque Growth Rates Due to Environmental Enteric Dysfunction and Association with Histopathology in the Large Intestine
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Researchers characterized environmental enteric (relating to the intestines) dysfunction (EED) among infant rhesus macaques (n=80, both sexes) naturally exposed to enteric pathogens commonly linked to human growth stunting. Despite atrophy and abnormalities observed in the small intestine, poor growth trajectories and low serum tryptophan (an amino acid needed for protein and enzymes) levels were correlated with increased histopathology (microscopic tissue examination for disease manifestation) in the large intestine.
Conjugation of HIV-1 Envelope to Hepatitis B Surface Antigen Alters Vaccine Responses in Rhesus Macaques
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Researchers are interested in developing an HIV-1 vaccine that improves upon the regimen used in the RV144 clinical trial. The authors tested the hypothesis that a conjugate vaccine based on the learned response to immunization with hepatitis B virus could be utilized to expand T-cell help and improve antibody production against HIV-1. Using juvenile rhesus macaques of both sexes, they evaluated the immunogenicity of their conjugate regimen.
A Defect in Mitochondrial Fatty Acid Synthesis Impairs Iron Metabolism and Causes Elevated Ceramide Levels
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Human mitochondrial enoyl coenzyme A reductase (Mecr), required for the last step of mitochondrial fatty acid synthesis (mtFAS), is linked to pediatric-onset neurodegeneration, but with unknown mechanisms. Researchers investigated phenotypes of mecr mutants in Drosophila and human-derived fibroblasts. They found that loss of function of Mecr in the whole body resulted in a defect in Fe-S cluster biogenesis and increased iron levels, leading to elevated ceramide levels and lethality in flies.
Large-Scale Production of Human Blastoids Amenable to Modeling Blastocyst Development and Maternal-Fetal Crosstalk
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Human blastoids provide a valuable model to study early human development and implantation with reduced genetic heterogeneity between samples. Investigators reported a protocol for efficient generation of high-fidelity human blastoids from naïve pluripotent stem cells. The similarities between blastoids and blastocysts in signaling activities—demonstrated using single-cell RNA sequencing—support the use of blastoids to model lineage differentiation and cavity formation.
The Contribution of Maternal Oral, Vaginal, and Gut Microbiota to the Developing Offspring Gut
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The maturation process of the gut microbiota (GM) is an essential process for life-long health that is defined by the acquisition and colonization of microorganisms in the gut and the subsequent immune system induction that occurs during early life. To address significant knowledge gaps in this area, investigators characterized the neonatal fecal and ileal microbiota of entire litters of mice at multiple pre-weaning time-points.
Effects of Acute Femoral Head Ischemia on the Growth Plate and Metaphysis in a Piglet Model of Legg-Calvé-Perthes Disease
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Legg-Calvé-Perthes disease (LCPD) can lead to permanent deformity of the femoral head and premature osteoarthritis, but the underlying cause remains unknown. More work is needed to determine optimal treatment methods for LCPD. Using a piglet model for LCPD, researchers assessed the effects of acute femoral head ischemia on the proximal femoral growth plate and metaphysis. They reported that alterations to the growth plate zones and metaphysis occurred by 2 days post-ischemia and persisted at 7 days post-ischemia.
Infection of the Maternal–Fetal Interface and Vertical Transmission Following Low-Dose Inoculation of Pregnant Rhesus Macaques (Macaca mulatta) with an African-Lineage Zika Virus
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Researchers examined transmission of Zika virus to nonhuman primate fetuses during pregnancy. Even with a low dosage of inoculation of the dams, the investigators found that the Zika virus infected fetuses, despite the presence of a “placental fortress,” which normally protects fetuses during gestation. This transmission illustrates the high level of infectivity threat that Zika poses, which may increase if mosquitoes expand their global habitats.
Giardia Hinders Growth by Disrupting Nutrient Metabolism Independent of Inflammatory Enteropathy
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Giardia lamblia is one of the most common intestinal pathogens among children in low- and middle-income countries. Investigators performed translational investigations using the Malnutrition and Enteric Diseases (MAL-ED) male and female cohort, as well as mice of both sexes, to identify mechanistic pathways that might explain Giardia-induced effects on early childhood growth. They identified signatures in the urinary metabolome of young children, suggesting that host growth restriction during infection is mediated by dysregulated amino acid metabolism.