Clinical characteristics of X-linked infantile nystagmus in a Chinese family / 上海交通大学学报（医学版）

Objective • To identify the clinical features of a Chinese Han family with X-linked infantile nystagmus. Methods • A Chinese family with X-linked infantile nystagmus was recruited from Department of Ophthalmology in Xinhua Hospital, Shanghai Jiao Tong University School of Medicine. Peripheral blood from the members of the family was collected and molecular genetic analysis was done. The 5 patients in the family received comprehensive ocular examinations including measurement of visual acuity, degree of anomalous head posture, stereoscopic vision, binocular function, electroretinogram, visual evoked potential, optical coherence tomography, eye movement recording and cycloplegic refraction. Results • A frame-shift mutation (c.823-829delACCCTAC, p.Thr275fs) in the 9th exon of FERM domain containing protein 7 (FRMD7) in the family was found. The similar clinical features of the family included moderate impairment of visual acuity, mild astigmatism, reduced stereoscopic vision, no fusion function, and bidirectional jerk wave form. Their electroretinograms were normal, but there was a peak latency and decreased amplitudes in visual evoked potential. And the structures of maculae had no obvious abnormality. The performance of the anomalous head posture was varied. Conclusion • Thr275fs in FRMD7 protein is identified as the main factor in the Chinese family with X-linked infantile nystagmus. The clinical features of the family show a certain degree of consistency.

Investigation of the influence of mechanical signals on the structure of CD44/FERM complex via molecular dynamics simulation / 生物医学工程学杂志

The intracellular domain of clusters of differentiation 44 (CD44) binding to the FERM (protein 4.1-ezrin-radixin-moesin) domain of ERM (ezrin/radixin/moesin) proteins and furthermore triggering the recruitment of spleen tyrosine kinase (Syk) are very important in the process of tumor cell adhesion, migration and proliferation. At first, it was found that CD44/FERM structure was stable by observing CD44/FERM complex conformation and analyzing the interaction of interface residues both in static crystal structure and in equilibrium process. Meanwhile, unconventional immunoreceptor tyrosine-based activation motif (ITAM-like), and phosphorylation sites Y191 and Y205 were buried in FERM domain, which would hinder the phosphorylation of ERM proteins, the recruitment of Syk and subsequent signal transduction. Then, steered molecular dynamics simulation was applied to simulate the interaction between CD44 and FERM domain in the mechanical environment. The results showed that mechanical signal could induce the exposure of the ITAM-like motif and phosphorylation site Y205 by tracking and analyzing CD44/FERM complex conformational changes and the solvent-accessible surface area. This study revealed how the force regulates the activation of downstream signal through CD44 intracellular domain for the first time, and would be useful for further understanding the adhesion and migration pathway of cancer cells and the design of antitumor drugs.

Human osteosarcoma multidrug resistance-related protein identified by differential in-gel electrophoresis / 中国肿瘤生物治疗杂志

Objective:To analyze the differential protein expression between multidrug-resistant human osteosarcoma MG-63/DXR100 and its parental cell line by differential in-gel electrophoresis,so as to lay a foundation for exploring the mechanism of multidrug resistance(MDR) of osteosarcoma.Methods:Multidrug-resistant clone of human osteosarcoma MG-63 was established by stepwise exposure to increasing doses of doxorubicin(DXR).The total proteins of the above two cell lines were separated with two-dimensional electrophoresis.The proteins of differential expression(increased or decreased by more than 30%) were analyzed with image scanning and DeCyder software.Then they were identified in MALDI-TOF Pro and Mascot database.Results:Thirty proteins with differential expression were identified by proteomic analysis,and 18 of them were further identified by MALDI-TOF Pro.Five protein spots were successfully identified:matrix metalloproteinases 1(MMP1) related with tumor cell metastasis,alcohol dehydrogenase(ADH6) with function of detoxication,FERM domain containing protein 3(FRMD3) which belongs to anti-oncogenes and two agnoproteins composed of 128 and 300 amino acid residues.MMP1,ADH6 and the two agnoproteins were over-expressed in MG-63/DXR100 group,and FRMD3 expression was lower than that in the MG-63 group.Conclusion:Five proteins including MMP1,ADH6,FRMD3 and two agnoproteins have been found abnormally expressed in MDR osteosarcoma cells by differential in-gel electrophoresis;they might participate in MDR of osteosarcoma.