No abstract

Eukaryotic mRNAs are 5′ end capped with a 7-methylguanosine, which is important for processing and translation of mRNAs. Cap methyltransferase 1 (CMTR1) catalyzes 2′-O-ribose methylation of the first transcribed nucleotide (N1 2′-O-Me) to mask mRNAs from innate immune surveillance by retinoic-acid-inducible gene-I (RIG-I). Nevertheless, whether this modification regulates gene expression for neuronal functions remains unexplored. Here, we find that knockdown of CMTR1 impairs dendrite development independent of secretory cytokines and RIG-I signaling. Using transcriptomic analyses, we identify altered gene expression related to dendrite morphogenesis instead of RIG-I-activated interferon signaling, such as decreased calcium/calmodulin-dependent protein kinase 2α ( Camk2α ). In line with these molecular changes, dendritic complexity in CMTR1-insufficient neurons is rescued by ectopic expression of CaMK2α but not by inactivation of RIG-I signaling. We further generate brain-specific CMTR1-knockout mice to validate these findings in vivo . Our study reveals the indispensable role of CMTR1-catalyzed N1 2′-O-Me in gene regulation for brain development.

Background: Sweating and increased skin temperature caused by exercise can reduce physical activity and the willingness to exercise in adolescents with atopic dermatitis. This study was conducted to investigate the exercise load capacity of adolescents with atopic dermatitis and analyzed their exercise behavior and motivation. Methods: Adolescents with and without atopic dermatitis were assigned to the atopic dermatitis group and control group (n = 27 each). Both groups completed a cardiopulmonary exercise test and questionnaires to assess their exercise capacity, weekly exercise volume, exercise motivation, and self-efficacy, respectively. Results: The ratio of measured forced vital capacity to the predicted forced vital capacity and the peak oxygen consumption of the atopic dermatitis group were significantly lower than those of the control group. The Godin Leisure-Time Exercise Questionnaire scores of the atopic dermatitis group were significantly lower than those of the control group. As for the Behavioral Regulation in Exercise Questionnaire 2, the scores for the introjected and identified regulations of the atopic dermatitis group were significantly lower than those of the control group. Regarding the Multidimensional Self-Efficacy for Exercise Scale, the scheduling efficacy and total scores of the atopic dermatitis group were significantly lower than those of the control group. Conclusions: Adolescents with atopic dermatitis had lower peak exercise capacity and lower weekly exercise volume. Furthermore, they lacked the negative feelings toward inactivity and the self-confidence to plan regular exercise independently. The results of this study suggest that adolescents with atopic dermatitis should be encouraged to engage in regular indoor exercise.

The surface modification of soft zwitterionic polymer brushes with antifouling properties represents a facile approach to enhancing the performance of bioelectronics. Ionic strength and applied potentials play a crucial role in controlling polymer brushes’ conformation and hydration states. In this study, we quantitatively investigated and compared poly­(2-methacryloyloxyethyl phosphorylcholine) (PMPC) and poly­(sulfobetaine methacrylate) (PSBMA) brushes at different salt concentrations and applied surface potentials. Initiator-containing poly­(3,4-ethylenedioxythiophene) films (poly­(EDOT-Br)) were prepared by electropolymerization. After the conducting polymer was deposited, polymer brushes grew from the electrode surface through surface-initiated atom-transfer radical polymerization (SI-ATRP). Polymer brushes were carefully characterized for their surface morphologies using an atomic force microscope (AFM). The force volume method measured using AFM enabled the analysis of the Young’s modulus of the two polymer brushes. Hydration states and protein binding behaviors of polymer brushes were examined using quartz crystal microbalance with dissipation (QCM-D). We further integrated a potentiostat with the QCM-D to conduct an electrochemical QCM-D study. The energy dissipation and frequency changes corresponded to the ion adsorption on the film surface under different ionic strengths. The results of both hydration states and nonspecific protein binding behavior indicate that PMPC brushes have greater ionic strength independency, implying the conformation of the unchanged PMPC brushes. Moreover, we illustrated how the surface potential influences nonspecific and specific binding behavior on PMPC brushes on PEDOT films compared with electrified poly­(EDOT-PC) electrodes. We concluded that PMPC brushes exhibit unique behaviors that are barely affected by ion concentration, and that the brushes’ modification results in less influence by surface potential due to the finite Debye length influencing the electrode surface to outer environment in an NaCl aqueous solution.