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Pharmacology role-playing, which follows a case and communication (C & C)-based approach, has been developed for use in medical education, and its learning effects have been reported. To cultivate team spirit among medical professionals from an early stage, we proposed developing the C & C approach for interprofessional education (IPE). Therefore, this study aimed to examine the learning effects of the C & C approach during joint classes of medical and nursing students. In December 2017, we employed the C & C approach to simulate a scenario in which drugs were explained to patients, and responses were collected from 103/115 medical (90%) and 55/60 nursing students (92%). The questionnaires used were designed to evaluate the following five items: understanding pharmacotherapy, understanding patients' feelings, learning motivation, change in learning attitudes, and understanding IPE. Open-ended questions on learning content were analyzed based on free-text responses. Each student group acknowledged the effectiveness of the approach and the importance of cooperation. In total, 80.2% of medical students and 76.3% of nursing rated "understanding of IPE" as "very effective/effective." Participants learned about the disparity in perspectives, with medical students gaining insight into nursing students' approaches to patient interactions, and nursing students acquiring an understanding of doctors' perspectives on disease and medical treatment. In conclusion, the C & C approach proved beneficial as an IPE method, raising awareness among both nursing and medical students about the significance of communication skills and patient perspectives. [ABSTRACT FROM AUTHOR]

Neural tube closure requires apical constriction during which contraction of the apical F-actin network forces the cell into a wedged shape, facilitating the folding of the neural plate into a tube. However, how F-actin assembly at the apical surface is regulated in mammalian neurulation remains largely unknown. We report here that formin homology 2 domain--containing 3 (Fhod3), a formin protein that mediates F-actin assembly, is essential for cranial neural tube closure in mouse embryos. We found that Fhod3 is expressed in the lateral neural plate but not in the floor region of the closing neural plate at the hindbrain. Consistently, in Fhod3-null embryos, neural plate bending at the midline occurred normally, but lateral plates seemed floppy and failed to flex dorsomedially. Because the apical accumulation of F-actin and constriction were impaired specifically at the lateral plates in Fhod3-null embryos, we concluded that Fhod3-mediated actin assembly contributes to lateral plate--specific apical constriction to advance closure. Intriguingly, Fhod3 expression at the hindbrain was restricted to neuromeric segments called rhombomeres. The rhombomere-specific accumulation of apical F-actin induced by the rhombomere-restricted expression of Fhod3 was responsible for the outward bulging of rhombomeres involving apical constriction along the anteroposterior axis, as rhombomeric bulging was less prominent in Fhod3-null embryos than in the wild type. Fhod3 thus plays a crucial role in the morphological changes associated with neural tube closure at the hindbrain by mediating apical constriction not only in the mediolateral but also in the anteroposterior direction, thereby contributing to tube closure and rhombomere segmentation, respectively. [ABSTRACT FROM AUTHOR]

Mutations in cardiac myosin-binding protein C (cMyBP-C) are a major cause of familial hypertrophic cardiomyopathy. Although cMyBP-C has been considered to regulate the cardiac function via cross-bridge arrangement at the C-zone of the myosin-containing A-band, the mechanism by which cMyBP-C functions remains unclear. We identified formin Fhod3, an actin organizer essential for the formation and maintenance of cardiac sarcomeres, as a cMyBP-C-binding protein. The cardiac-specific N-terminal Ig-like domain of cMyBP-C directly interacts with the cardiac-specific N-terminal region of Fhod3. The interaction seems to direct the localization of Fhod3 to the C-zone, since a noncardiac Fhod3 variant lacking the cMyBP-C-binding region failed to localize to the C-zone. Conversely, the cardiac variant of Fhod3 failed to localize to the C-zone in the cMyBP-C-null mice, which display a phenotype of hypertrophic cardiomyopathy. The cardiomyopathic phenotype of cMyBP-C-null mice was further exacerbated by Fhod3 overexpression with a defect of sarcomere integrity, whereas that was partially ameliorated by a reduction in the Fhod3 protein levels, suggesting that Fhod3 has a deleterious effect on cardiac function under cMyBP-C-null conditions where Fhod3 is aberrantly mislocalized. Together, these findings suggest the possibility that Fhod3 contributes to the pathogenesis of cMyBP-C-related cardiomyopathy and that Fhod3 is critically involved in cMyBP-C-mediated regulation of cardiac function via direct interaction. [ABSTRACT FROM AUTHOR]

Cardiac development and function require actin-myosin interactions in the sarcomere, a highly organized contractile structure. Sarcomere assembly mediated by formin homology 2 domain-containing 3 (Fhod3), a member of formins that directs formation of straight actin filaments, is essential for embryonic cardiogenesis. However, the role of Fhod3 in the neonatal and adult stages has remained unknown. Here, we generated floxed Fhod3 mice to bypass the embryonic lethality of an Fhod3 knockout (KO). Perinatal KO of Fhod3 in the heart caused juvenile lethality at around day 10 after birth with enlarged hearts composed of severely impaired myofibrils, indicating that Fhod3 is crucial for postnatal heart development. Tamoxifen-induced conditional KO of Fhod3 in the adult heart neither led to lethal effects nor did it affect sarcomere structure and localization of sarcomere components. However, adult Fhod3-deleted mice exhibited a slight cardiomegaly and mild impairment of cardiac function, conditions that were sustained over 1 year without compensation during aging. In addition to these age-related changes, systemic stimulation with the α1-adrenergic receptor agonist phenylephrine, which induces sustained hypertension and hypertrophy development, induced expression of fetal cardiac genes that was more pronounced in adult Fhod3-deleted mice than in the control mice, suggesting that Fhod3 modulates hypertrophic changes in the adult heart. We conclude that Fhod3 plays a crucial role in both postnatal cardiac development and functional maintenance of the adult heart. [ABSTRACT FROM AUTHOR]

The superoxide-producing NADPH oxidase in phagocytes is crucial for host defence; its catalytic core is the membrane-integrated protein gp91phox[also known as Nox2 (NADPH oxidase 2)], which forms a stable heterodimer with p22phox. Activation of the oxidase requires membrane translocation of the three cytosolic proteins p47phox, p67phoxand the small GTPase Rac. At the membrane, these proteins assemble with the gp91phox–p22phoxheterodimer and induce a conformational change of gp91phox, leading to superoxide production. p47phoxtranslocates to membranes using its two tandemly arranged SH3 domains, which directly interact with p22phox, whereas p67phoxis recruited in a p47phox-dependent manner. In the present study, we show that a short region N-terminal to the bis-SH3 domain is required for activation of the phagocyte NADPH oxidase. Alanine substitution for Ile152in this region, a residue that is completely conserved during evolution, results in a loss of the ability to activate the oxidase; and the replacement of Thr153also prevents oxidase activation, but to a lesser extent. In addition, the corresponding isoleucine residue (Ile155) of the p47phoxhomologue Noxo1 (Nox organizer 1) participates in the activation of non-phagocytic oxidases, such as Nox1 and Nox3. The I152A substitution in p47phox, however, does not affect its interaction with p22phoxor with p67phox. Consistent with this, a mutant p47phox(I152A), as well as the wild-type protein, is targeted upon cell stimulation to membranes, and membrane recruitment of p67phoxand Rac normally occurs in p47phox(I152A)-expressing cells. Thus the Ile152-containing region of p47phoxplays a crucial role in oxidase activation, probably by functioning at a process after oxidase assembly. [ABSTRACT FROM AUTHOR]