bioRxiv ScienceSearch

Biology subjects

Turner, M.

Publications and source records attributed to Turner, M..

2 recordsLinked to original sources

Resting-State Brain Fluctuation and Functional Connectivity Dissociate Moral Injury from Posttraumatic Stress Disorder

Moral injury is closely associated with posttraumatic stress disorder (PTSD) and is characterized by disturbances in social and moral cognition. Little is known about the neural underpinnings of moral injury, and whether the neural correlates are different between moral injury and PTSD.\n\nA sample of 26 US military veterans (2 females; 28~55 years old) were investigated to determine how moral injury experiences and PTSD symptoms are differentially related to spontaneous fluctuations indexed by low frequency fluctuation (ALFF) as well as functional connectivity during resting-state functional magnetic resonance imaging (fMRI) scanning.\n\nALFF in the left inferior parietal lobule (L IPL) was positively associated with moral injury sub-scores of transgressions, negatively associated with sub-scores of betrayals, and not related with PTSD symptoms. Moreover, functional connectivity between the L IPL and bilateral precuneus was positively related with PTSD symptoms and negatively related with moral injury total scores.\n\nOur results provide the first evidence that moral injury and PTSD have dissociable neural underpinnings, and behaviorally distinct sub-components of moral injury are different in neural responses. The findings increase our knowledge of the neural distinctions between moral injury and PTSD and may contribute to developing nosology and interventions for military veterans afflicted with moral injury.

neuroscience

Alternative translation initiation generates a functionally distinct isoform of the stress-activated kinase MK2

Shaping of the proteome by alternative translation is an important mechanism of post-transcriptional gene regulation. It can lead to the expression of multiple protein isoforms originating from the same mRNA. Here we show that a novel, abundant and long isoform of the stress/p38MAPK-activated kinase MK2, a key regulator of transcription, migration, death signaling and post-transcriptional gene regulation, is constitutively translated from an alternative CUG translation initiation start site located in the 5'UTR of its mRNA. GC-rich sequences and putative G-quadruplex structures influence the usage of that codon as a translation initiation start site and the RNA helicase eIF4A1 is needed to ensure alternative isoform translation. We recapitulated the usage of the alternative start codon and determined the molecular properties of the short and a long MK2 isoforms. Phenotypically, only the short isoform phosphorylated Hsp27, supported migration and stress-induced immediate early gene (IEG) expression. Interaction profiling by quantitative mass-spectrometry revealed short isoform-specific binding partners that were associated with migration. In contrast, the long isoform contains additional putative phosphorylation sites in its unique N-terminus. In sum, our data reveal a longer and previously non-described isoform of MK2 with distinct physiological properties originating from alternative translation.

molecular biology