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- Down Syndrome
- Pediatrics
Multimodal Analysis of Dysregulated Heme Metabolism, Hypoxic Signaling, and Stress Erythropoiesis in Down Syndrome
Donovan et al., Cell Reports. 2024.
https://pubmed.ncbi.nlm.nih.gov/39120971
Down syndrome (DS), a genetic condition caused by the presence of an extra copy of chromosome 21, is characterized by intellectual and developmental disability. Infants with DS often suffer from low oxygen saturation, and DS is associated with obstructive sleep apnea. Investigators assessed the role that hypoxia plays in driving health conditions that are comorbid with DS. A multiomic analysis showed that people with DS exhibit elevated heme metabolism and activated stress erythropoiesis, which are indicators of chronic hypoxia; these results were recapitulated in a mouse model for DS. This study identified hypoxia as a possible mechanism underlying several conditions that co-occur with DS, including congenital heart defects, seizure disorders, autoimmune disorders, several leukemias, and Alzheimer's disease. Supported by ORIP (R24OD035579), NCATS, NCI, and NIAID.
Effects of Acute Femoral Head Ischemia on the Growth Plate and Metaphysis in a Piglet Model of Legg-Calvé-Perthes Disease
Armstrong et al., Osteoarthritis and Cartilage. 2023.
https://pubmed.ncbi.nlm.nih.gov/36696941/
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. These findings suggest that growth disruption may occur sooner after the onset of ischemia than researchers had hypothesized previously. Supported by ORIP (T32OD010993, K01OD021293), NIAMS, and NCATS.
The Early Life Microbiota Mediates Maternal Effects on Offspring Growth in a Nonhuman Primate
Petrullo et al., iScience. 2022.
https://www.doi.org/10.1016/j.isci.2022.103948
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. Researchers found that first-time vervet mothers harbored a milk bacterial community that was less diverse due to the dominance of Bacteroides fragilis, a glycan-utilizing bacteria. These low-parity females had infants that grew faster, suggesting that vertical transmission of bacteria via milk can mediate maternal effects on growth. These results indicate non-nutritive milk constituents play important roles in development. Commercial milk formula might need to be improved or supplemented to better support infant health. Supported by ORIP (P40OD010965) and NCATS.