1.
Full-length isoform transcriptome of the developing human brain provides further insights into autism.
Chau, KK, Zhang, P, Urresti, J, Amar, M, Pramod, AB, Chen, J, Thomas, A, Corominas, R, Lin, GN, Iakoucheva, LM
Cell reports. 2021;(9):109631
Abstract
Alternative splicing plays an important role in brain development, but its global contribution to human neurodevelopmental diseases (NDDs) requires further investigation. Here we examine the relationships between splicing isoform expression in the brain and de novo loss-of-function mutations from individuals with NDDs. We analyze the full-length isoform transcriptome of the developing human brain and observe differentially expressed isoforms and isoform co-expression modules undetectable by gene-level analyses. These isoforms are enriched in loss-of-function mutations and microexons, are co-expressed with a unique set of partners, and have higher prenatal expression. We experimentally test the effect of splice-site mutations and demonstrate exon skipping in five NDD risk genes, including SCN2A, DYRK1A, and BTRC. Our results suggest that the splice site mutation in BTRC reduces translational efficiency, likely affecting Wnt signaling through impaired degradation of β-catenin. We propose that functional effects of mutations should be investigated at the isoform- rather than gene-level resolution.
2.
Processing of food, body and emotional stimuli in anorexia nervosa: a systematic review and meta-analysis of functional magnetic resonance imaging studies.
Zhu, Y, Hu, X, Wang, J, Chen, J, Guo, Q, Li, C, Enck, P
European eating disorders review : the journal of the Eating Disorders Association. 2012;(6):439-50
Abstract
The characteristics of the cognitive processing of food, body and emotional information in patients with anorexia nervosa (AN) are debatable. We reviewed functional magnetic resonance imaging studies to assess whether there were consistent neural basis and networks in the studies to date. Searching PubMed, Ovid, Web of Science, The Cochrane Library and Google Scholar between January 1980 and May 2012, we identified 17 relevant studies. Activation likelihood estimation was used to perform a quantitative meta-analysis of functional magnetic resonance imaging studies. For both food stimuli and body stimuli, AN patients showed increased hemodynamic response in the emotion-related regions (frontal, caudate, uncus, insula and temporal) and decreased activation in the parietal region. Although no robust brain activation has been found in response to emotional stimuli, emotion-related neural networks are involved in the processing of food and body stimuli among AN. It suggests that negative emotional arousal is related to cognitive processing bias of food and body stimuli in AN.