ABSTRACT
The human dual specificity tyrosine phosphorylation regulated kinase 1A (DYRK1A) is implicated in the pathology of Down syndrome, microcephaly, and cancer, however the exact mechanism through which it functions is unknown. Here, we have studied the role of the Drosophila ortholog of DYRK1A, Minibrain (Mnb), in brain development. The neuroblasts (neural stem cells) that eventually give rise to differentiated neurons in the adult brain are formed from a specialized tissue in the larval optic lobe called the neuroepithelium, in a tightly regulated process. Molecular marker analysis of mnb mutants revealed alterations in the neuroepithelium and neuroblast regions of developing larval brains. Using affinity purification-mass spectrometry (AP-MS), we identified the novel Mnb binding partners Ral interacting protein (Rlip) and RALBP1 associated Eps domain containing (Reps). Rlip and Reps physically and genetically interact with Mnb, and the three proteins may form a ternary complex. Mnb phosphorylates Reps, and human DYRK1A binds to the Reps orthologs REPS1 and REPS2. Furthermore, Mnb engages the small GTPase Ras-like protein A (Rala) to regulate brain and wing development. This work uncovers a previously unrecognized early role of Mnb in the neuroepithelium and defines the functions of the Mnb/Reps/Rlip/Rala signaling network in brain development. Significance statement: The kinase Minibrain(Mnb)/DYRK1A regulates the development of the brain and other tissues across many organisms. Here we show the critical importance of Mnb within the developing neuroepithelium. Advancing our understanding of Mnb function, we identified novel protein interactors of Mnb, Reps and Rlip, which function together with Mnb to regulate growth in Drosophila melanogaster . We also identify and characterize a role for the small GTPase Rala in Mnb-regulated growth and nervous system development. This work reveals an early role of Mnb in brain development and identifies a new Mnb/Reps/Rlip/Rala signaling axis.
ABSTRACT
INTRODUCTION: This study aimed to evaluate the short-term impact of different incision positions on astigmatism and visual quality after small incision lenticule extraction (SMILE) surgery. METHODS: This prospective study enrolled patients who decided to have SMILE to correct myopia. Patients were randomly allocated into three groups of different incision positions (group A, B, and C with incision position at 90°, 120°, and 150° respectively). Preoperative and postoperative visual acuity, spherical equivalent, and high-order aberrations (HOAs) were measured and compared among groups. Astigmatism was analyzed with the ASSORT Group Analysis Calculator based on the Alpins method. RESULTS: A total of 148 eyes were included for analysis (48 eyes in group A, 50 eyes in group B, and 50 eyes in group C). At 1 month postoperatively, the mean uncorrected distance visual acuity (UDVA) logMAR in group A, B, and C was - 0.03, - 0.03, and - 0.04, respectively. The mean corrected distance visual acuity (CDVA) logMAR in group A, B, and C was - 0.03, - 0.04, and - 0.04, respectively (P > 0.05). The mean postoperative spherical equivalent (SE) values were - 0.01 ± 0.38, - 0.07 ± 0.39, and - 0.16 ± 0.49 (D) in group A, B, and C, respectively (P > 0.05). There was no statistically significant difference in preoperative and postoperative magnitude of astigmatism among different groups (P > 0.05). Significant differences were found in the distribution of astigmatism axis among the three groups at 1 day (P = 0.02) and 1 week (P = 0.02) postoperatively. However, such differences were no longer significant at 1 month after surgery (P > 0.05). No significant differences were found in HOAs among different groups 1 month after surgery (P > 0.05). CONCLUSION: Different incision positions have no effect on postoperative astigmatism and visual quality 1 month after SMILE surgery, though differences were found in the distribution of the astigmatism axis within 1 week after the surgery.
ABSTRACT
BACKGROUND: The gut visceral musculature plays essential roles in not only moving substances through the lumen but also maintaining the function and physiology of the gut. Although the development of the visceral musculature has been studied in multiple model organisms, how it degenerates is poorly understood. RESULTS: Here, we employ the Drosophila midgut as a model to demonstrate that the visceral musculature is disrupted by intrinsic and extrinsic factors, such as aging, feeding, chemical-induced tissue damage, and oncogenic transformation in the epithelium. Notably, we define four prominent visceral musculature disruption phenotypes, which we refer as "sprout," "discontinuity," "furcation," and "crossover" of the longitudinal muscle. Given that the occurrence of these phenotypes is increased during aging and under various stresses, we propose that these phenotypes can be used as quantitative readouts of deterioration of the visceral musculature. Intriguingly, administration of a tissue-damaging chemical dextran sulfate sodium (DSS) induced similar visceral musculature disruption phenotypes in zebrafish larvae, indicating that ingestion of a tissue-damaging chemical can disrupt the visceral musculature in a vertebrate as well. CONCLUSIONS: Our study provides insights into the deterioration of the gut visceral musculature and lays a groundwork for investigating the underlying mechanisms in Drosophila as well as other animals.
