Maternal prenatal immune activation associated with brain tissue microstructure and metabolite concentrations in newborn infants.

Few human studies have assessed the association of prenatal maternal immune activation (MIA) with measures of brain development and psychiatric risk in newborn offspring. Our goal was to identify the effects of MIA during the 2nd and 3rd trimesters of pregnancy on newborn measures of brain metabolite concentrations, tissue microstructure, and motor development. This was a prospective longitudinal cohort study conducted with nulliparous pregnant women who were aged 14 to 19 years and recruited in their 2nd trimester, as well as their children who were followed through 14 months of age. MIA was indexed by maternal interleukin-6 (IL-6) and C-reactive protein (CRP) in both trimesters of pregnancy. Primary outcomes included: (1) newborn brain metabolite concentrations as ratios to creatine (N-acetylaspartate (NAA)/creatine (Cr) and choline (Cho)/Cr) measured using Magnetic Resonance Spectroscopy; (2) newborn fractional anisotropy and mean diffusivity, measured using Diffusion Tensor Imaging; and (3) indices of motor development, assessed prenatally and postnatally at ages 4- and 14-months. Maternal IL-6 and CRP levels associated significantly with both metabolites in the putamen, thalamus, insula, and the internal capsule. Maternal IL-6 associated significantly with fractional anisotropy in the putamen, caudate, thalamus, insula, and precuneus, and with mean diffusivity in the inferior parietal and middle temporal gyrus. CRP associated significantly with fractional anisotropy in the thalamus, insula, and putamen. Significant associations were found in common regions across imaging modalities, though the direction of associations differed by immune marker. In addition, both maternal IL-6 and CRP (in both trimesters) prenatally associated significantly with offspring motor development at 4- and 14-months of age. The left thalamus mediated effects of IL-6 on postnatal motor development. These findings demonstrate that levels of MIA in mid- to late pregnancy in a generally healthy sample associate with tissue characteristics in newborn brain regions that primarily support motor integration and coordination, as well as behavioral regulation. Those brain effects may contribute to differences in motor development.

Informing Equitable Prevention Practices: A Statewide Disaggregated Analysis of Suicide for Ethnoracially Minoritized Adolescents.

The increase in adolescent suicide rates in the United States is a pervasive public health issue, and ethnoracial youth with diverse identities are disproportionately impacted, yet less studied. National planning efforts reinforce state-level approaches to suicide prevention through an equitable lens to prevent adolescent suicide. This study examined disaggregated state-level data over time to determine changes to suicide outcomes based on race/ethnicity, sex, sexual orientation, and the intersection of these identities and determined which sub-groups had higher odds of suicide outcomes. Data from the 1991-2019 Centers for Disease Control and Prevention Youth Risk Behavioral Surveillance System were analyzed for 17,419 ethnoracially minoritized high school adolescents in North Carolina. Descriptive analyses and multinominal logistic regression models were employed. Findings indicated that subgroups within categories of ethnoracial populations, specifically Black female adolescents unsure of their sexual orientation, reported higher rates of suicide attempts. Additionally, Multiracial adolescents reported higher means for suicide consideration and attempts over time. Recommendations for investigating state-level suicide data by focusing on diverse intersecting identities to illuminate areas for potential prevention efforts and support health equity are provided.

Non-muscle myosin 2 can incorporate into established filaments in cells without an assembly competence domain.

Myosin 2 dynamically assembles into filaments that exert force on the actin cytoskeleton. To form filaments, myosin 2 monomers transition between folded and unfolded states. Monomer unfolding exposes an extended coiled-coil that interacts with other monomers in parallel and antiparallel fashions, enabling bipolar filament formation. A C-terminal domain of the coiled-coil, termed assembly competence domain (ACD), has been repeatedly identified as necessary for filament assembly. Here, we revisit ACD contribution when full-length filaments are present. Non-muscle myosin 2A lacking the ACD (ΔACD) initially appears diffuse, but triton extraction of cytosolic fraction reveals cytoskeletal association. Disruption of the folded monomer enhances the cytoskeletal fraction, while inhibition of endogenous filament assembly appears to reduce it. Finally, high resolution imaging of endogenous and exogenous bipolar filamentous structures reveals highly coincident signal, suggesting ΔACD constructs co-assemble with endogenous myosin 2A filaments. Our data demonstrate that while the ACD is required for de novo filament assembly, it is not required for monomers to recognize and associate with established filaments in cells. More broadly, this highlights the existence of distinct mechanisms governing myosin 2 monomer assembly into nascent filaments, and monomer recognition and association with established filaments to maintain steady-state contractile networks.