NESCA, a newly discovered signaling adapter protein in the NGF-pathway, contains a RUN domain at its N-terminus. Here we report the crystal structure of the NESCA RUN domain determined at 2.0-Å resolution. The overall fold of the NESCA RUN domain comprises nine helices, resembling the RUN domain of RPIPx and the RUN1 domain of Rab6IP1. However, compared to the other RUN domains, the RUN domain of NESCA has significantly different surface electrostatic distributions at the putative GTPase-interacting interface. We demonstrate that the RUN domain of NESCA can bind H-Ras, a downstream signaling molecule of TrkA, with high affinity. Moreover, NESCA RUN can directly interact with TrkA. These results provide new insights into how NESCA participates in the NGF-TrkA signaling pathway.
Adaptor Proteins, Signal Transducing ; chemistry ; genetics ; metabolism ; Amino Acid Sequence ; Binding Sites ; Crystallography, X-Ray ; Gene Expression ; Humans ; Models, Molecular ; Molecular Sequence Data ; Nerve Growth Factor ; chemistry ; genetics ; metabolism ; Oncogene Protein p21(ras) ; chemistry ; genetics ; metabolism ; Protein Binding ; Protein Structure, Tertiary ; Receptor, trkA ; chemistry ; genetics ; metabolism ; Recombinant Proteins ; chemistry ; genetics ; metabolism ; Sequence Homology, Amino Acid ; Signal Transduction ; rab GTP-Binding Proteins ; chemistry

Objective:To promote the development of basic research, clarify the development trend of frontier biotechnology, and strengthen scientific research management in project management, resource integration, risk supervision and other aspects.Methods:Through literature study and expert discussion, this paper analyzed the hot spots of frontier biotechnology research, and put forward suggestions for optimizing strategic tasks and innovation management from the perspective of innovation management.Results:The research of frontier biotechnology in our country showed a rapid development trend, but also faced with challenges such as insufficient technological innovation ability and relatively lagging management level. It is imperative to explore and establish a new scientific research management model and optimize the operation mechanism.Conclusions:The major research achievements of frontier biotechnology are emerging constantly, showing a trend of multi-disciplinary and multi-field integration. China should actively explore innovative management models, optimize and improve strategic tasks, improve the efficiency of scientific research management, and do a good job in supporting the realization of high-level scientific and technological self-reliance.

Objective:To design a new V-shaped forearm flap and to investigate the possibility of direct donor site closure and its value in the reconstruction of soft tissue defect after resection of buccal carcinoma.Methods:The new V-shaped forearm flap technique was applied in 10 patients with buccal carcinoma from October, 2018 to September, 2019. There were 6 males and 4 females aged from 35 to 63 years (48.3 years in average). Flap size ranged from 3.0 cm×5.0 cm to 4.0 cm×6.0 cm. Wound healing and the appearance forearm were recorded and evaluated three months after the surgery. Radial deviation angle, wrist flexion, ulnar deviation and dorsal extension were measured and calculated 3 months after the surgery. The wrist function was evaluated according to the Gartland-Werley scale. The recovery of wrist function was evaluated by comparing with the preoperative data.Results:Forearm donor sites were successfully closed without skin grafting in all 10 patients. Skin ischemia caused by excessive tension was observed at the incision edge in 3 patients, therefore leading to skin exfoliation and pigment loss without affecting wound healing. All patients were presented a cosmetic outcome during the follow-up period. No scar hyperplasia was observed. No significant difference was observed in perioperative wrist flexion angle, dorsal extension angle, radial deviation angle, ulnar deviation angle ( P>0.05)[data before surgery were (57.8±1.3) °, (58.4±0.7) °, (18.2±0.5) °, (28.5±1.1) ° respectively, and data 3 months after surgery were (53.2±2.1) °, (55.3±1.8) °, (16.4±0.4) °, (25.4±1.4) ° respectively]; Excellent and good rate of Gartland-Werley wrist score before and after surgery were both 100%. Conclusion:The new V-shaped free forearm flap can directly close small to medium forearm flap donor site. This method could avoid the trauma and complications of traditional free skin graft. The postoperative appearance on donor site is satisfactory and will not have adverse effects on wrist function. The new V-shaped free forearm flap is a novel method for repair of the defect of soft tissue defect after buccal cancer and it is worth to be applied in clinical practice.