Notch Missense Mutations in Drosophila Reveal Functions of Specific EGF-like Repeats in Notch Folding, Trafficking, and Signaling.

Notch signaling plays various roles in cell-fate specification through direct cell-cell interactions. Notch receptors are evolutionarily conserved transmembrane proteins with multiple epidermal growth factor (EGF)-like repeats. Drosophila Notch has 36 EGF-like repeats, and while some play a role in Notch signaling, the specific functions of most remain unclear. To investigate the role of each EGF-like repeat, we used 19 previously identified missense mutations of Notch with unique amino acid substitutions in various EGF-like repeats and a transmembrane domain; 17 of these were identified through a single genetic screen. We assessed these mutants' phenotypes in the nervous system and hindgut during embryogenesis, and found that 10 of the 19 Notch mutants had defects in both lateral inhibition and inductive Notch signaling, showing context dependency. Of these 10 mutants, six accumulated Notch in the endoplasmic reticulum (ER), and these six were located in EGF-like repeats 8-10 or 25. Mutations with cysteine substitutions were not always coupled with ER accumulation. This suggests that certain EGF-like repeats may be particularly susceptible to structural perturbation, resulting in a misfolded and inactive Notch product that accumulates in the ER. Thus, we propose that these EGF-like repeats may be integral to Notch folding.

Assessment of autonomic nervous system function in nursing students using an autonomic reflex orthostatic test by heart rate spectral analysis.

Nursing students experience academic demands, such as tests, theoretical and practical coursework, research activities, various aspects of professional practice, and contact with health professionals and patients. Consequently, nursing students face numerous types of stress, and increased stress levels contribute to physical and psychological distress in nursing students. The aim of the present study was to investigate the autonomic nervous system function of nursing students by assessing active standing load using the autonomic reflex orthostatic tolerance test, which enables quantitative analysis of dynamic autonomic nervous system function. The autonomic nervous system activity in the resting state was low in fourth-year students, they had parasympathetic hypotension, and there was a tendency towards higher sympathetic nervous system activity of fourth-year students compared with first-, second- and third-year students. In the standing state, there was a trend towards a higher autonomic nervous system activity response of fourth-year students compared with first-, second- and third-year students. These results suggest that stress may influence autonomic nervous activity in fourth-year nursing students. By correcting stress in fourth-year nursing students, it may be possible to prevent the development of health problems.