Miller, S. P. | Search bioRxiv

bioRxiv2020

Delayed maturation of the structural brain connectome in neonates with congenital heart disease

There is emerging evidence for delayed brain development in neonates with congenital heart disease (CHD). We hypothesize that the perioperative development of the structural brain connectome is a proxy to such delays. Therefore, we set out to quantify the alterations and longitudinal pre- to postoperative changes in the connectome in CHD neonates and assess risk factors for disturbed perioperative network development relative to healthy term newborns. In this prospective cohort study, 114 term neonates with CHD underwent cardiac surgery at the University Childrens Hospital Zurich. Forty-six healthy term newborns were included as controls. Pre- and postoperative structural connectomes were derived from mean fractional anisotropy values of fibre pathways traced using diffusion tractography. Graph theory parameters calculated across a range of proportional cost thresholds were compared between groups by multi-threshold permutation correction adjusting for con-founders. Network based statistic was calculated for edgewise network comparison. White matter injury (WMI) volume was quantified on 3D T1-weighted images. Random coefficient mixed models with interaction terms of (i) CHD subtype and (ii) WMI volume with postmenstrual age at MRI respectively were built to assess modifying effects on network development. Pre- and postoperatively, at the global level, efficiency, indicative of network integration, was higher in controls compared to CHD neonates. In contrast, local efficiency and transitivity, indicative of network segregation, were higher in CHD neonates compared to controls (all p<0.025 for one-sided t-tests). Preoperatively these group differences were also found across multiple widespread nodes (all p<0.025, accounting for multiple comparison), whereas postoperatively nodal differences were not evident. At the edge-level, the majority of weaker connections in CHD neonates compared to controls involved interhemispheric connections (66.7% preoperatively; 54.5% postoperatively). A trend showing a more rapid pre- to postoperative decrease in local efficiency was found in class I CHD neonates compared to controls. In CHD neonates, larger WMI volume was associated with lower strength (p=0.0026) and global efficiency (p=0.0097). The maturation of the structural connectome is delayed in neonates with CHD, with a pattern of lower structural integration and higher segregation compared to healthy controls. Trend-level evidence indicated that normalized postoperative cardiac physiology in class I CHD neonates might improve structural network topology. In contrast, the degree of WMI burden negatively impacts network strength and integration. Further research is needed to elucidate how aberrant structural network development in CHD represents neural correlates of later neurodevelopmental impairments.

neuroscience↗

bioRxiv2020

Development of a genetic evaluation for hair shedding in American Angus cattle to improve thermotolerance

BackgroundHeat stress and fescue toxicosis caused by ingesting tall fescue infected with the endophytic fungus Epichloe coenophiala represent two of the most prevalent stressors to beef cattle in the United States, costing the beef industry millions of dollars each year. The rate at which a beef cow sheds her winter coat early in the summer is an indicator of adaptation to heat and an economically relevant trait in many parts of the U.S. Further, research suggests that early-summer hair shedding may be reflective of tolerance to fescue toxicosis, as vasoconstriction induced by fescue toxicosis limits the ability of an animal to shed its winter coat. Here, we developed parameters for routine genetic evaluation of hair shedding score in American Angus cattle and identified genomic loci associated with variation in hair shedding score via genome-wide association analysis (GWAA). ResultsHair shedding score was found to be moderately heritable (h2 = 0.34 to 0.40), with differing repeatability estimates between cattle grazing versus not grazing endophyte-infected tall fescue. Our results suggest modestly negative genetic and phenotypic correlations between a dams hair shedding score (lower score is earlier shedding) and the weaning weight of her calf, one metric of performance. Together, these results indicate that economic gains can be made via the use of hair shedding score breeding values to select for heat tolerant cattle. GWAA identified 176 variants significant at FDR < 0.05. Functional enrichment analyses using genes within 50 Kb of these variants identified pathways involved in keratin formation, prolactin signaling, host-virus interaction, and other biological processes. ConclusionsThis work contributes to a continuing trend in the development of genetic evaluations for environmental adaptation. The results of this work will aid beef cattle producers in selecting more sustainable and climate-adapted cattle, as well as enable the development of similar routine genetic evaluations in other breeds.

genomics↗