Emotional reactivity and regulation are fundamental to human behavior. As inter-individual behavioral variation is affected by a multitude of different genes, there is intense interest to investigate gene-gene effects. Functional sequence variation at two genes has been associated with response and resiliency to emotionally unpleasant stimuli. These genes are the catechol-O-methyltransferase gene (COMT Val 158 Met) and the regulatory region (5-HTTLPR) of the serotonin transporter gene. Recently, it has been proposed that 5-HTT expression is not only affected by the common S/L variant of 5-HTTLPR but also by an A to G substitution. Using functional magnetic resonance imaging, we assessed the effects of COMT Val 158 Met and both 5-HTT genotypes on brain activation by standardized affective visual stimuli (unpleasant, pleasant, and neutral) in 48 healthy subjects. Based on previous studies, the analysis of genotype effects was restricted to limbic brain areas. To determine allele-dose effects, the number of COMT Met 158 alleles (i.e., lower activity of COMT) and the number of 5-HTT low expressing alleles (S and G) was correlated with the blood oxygen level-dependent (BOLD) response to pleasant or unpleasant stimuli compared to neutral stimuli. We observed an additive effect of COMT and both 5-HTT polymorphisms, accounting for 40% of the interindividual variance in the averaged BOLD response of amygdala, hippocampal and limbic cortical regions elicited by unpleasant stimuli. Effects of 5-HTT and COMT genotypes did not affect brain processing of pleasant stimuli. These data indicate that functional brain imaging may be used to assess the interaction of multiple genes on the function of neuronal networks.
hippocampus of schizophrenia patients in post-mortem studies. 5 Furthermore, DISC1 has previously been shown to directly regulate the GSK3ß signalling pathway with downstream effects on neurogenesis. 6 NRG1-ErbB signalling is also known to interact with the Wnt-GSK3ß signalling pathway, 4 and genetic variants altering NRG1 expression have been implicated in a range of neuropsychiatric disorders. 3 Recently Makinodan et al. 7 have shown that prolonged social isolation in mice during the juvenile period (PND 21-35) resulted in decreased Type III neuregulin expression in the prefrontal cortex and impaired oligodendroctye development and myelination. Here we show that even a relative brief exposure to non-social stressors during the juvenile period is sufficient to produce a selective decrease in NRG1 Type III expression. Taken together, these findings suggest that a wide range of pre-pubertal stressors can produce long-lasting effects on the expression of psychiatric risk genes, with significant implications for brain myelination and development and risk for later psychiatric disorder.
ABSTRACT. Calcium is one of the most abundant minerals in the human body, playing a critical role in many cellular activities by interacting with different calcium ion (Ca 2+ )-binding proteins. Therefore, the correct identification of Ca 2+ -binding residues is essential for protein functional research. In this study, a new method was developed to predict Ca 2+ -binding residues from the primary sequence without using three-dimensional information. Through statistical analysis, four kinds of feature parameters were extracted from amino acid sequences: the increment of diversity values of amino acid composition, the matrix scoring values of position conservation, the autocross covariance of physicochemical properties, and the center motif. These features served as input for a support vector machine to predict Ca 2+ -binding residues. This method was tested on four well-established datasets using a five-fold cross-validation. The accuracies and Matthews correlation coefficients were 75.9% and 0.53 (dataset 1), 79.2% and 0.58 (dataset 2), 77.4% and 0.55 (dataset 3), and 79.1% and 0.58 (dataset 4). Comparative results show that the developed method outperforms previous methods. Based on this study, a web server was developed for predicting Ca 2+ -binding
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.