Objective To study the characteristics and influencing factors of event-related potential (ERP) P300 in patients with obstructive sleep apnea hypopnea syndrome (OSAHS).Methods Twenty-two OSAHS patients (OSAHS group) and 18 healthy subjects (control group) were recruited,and the ERP P300 was recorded with all the subjects.The correlation between latency and amplitude of P300 and influencing factors including variation of sleep mode,apnea hypopnea index (AHI),mean oxyhemoglobin saturation level(MSaO2),the lowest of oxyhemoglobin saturation level (LSaO2),time of non-rapid eye movement (NREM) sleep Ⅰ,Ⅱ,Ⅲ,Ⅳ stage and rapid eye movement (REM) sleep over total sleep time and total sleep time of SaO2 ＜ 90％ (90％ SaO2) were analyzed by using linear regression correlation analysis and multiple stepwise regression analysis.Results The latencies of P3 component of P300 in OSAHS group were longer than that of control group[(344.24 ± 23.99)ms versus (311.17 ± 15.65) ms] (P＜ 0.05),while the amplitudes were decreased and lower in OSAHS group than that in control group [(3.66 ± 1.49) μV versus (6.26 ± 1.48) μV] (P ＜ 0.05).There revealed positive correlations between P3 latency and NREM Ⅰ and Ⅱ (r=0.492,P＜0.05),90％SaO2(r=0.627,P＜0.01),AHI(r=0.882,P＜0.01); negative correlation between P3 latency and NREM Ⅲ and Ⅳ (r =-0.558,P ＜ 0.01),LSaO2,(r =-0.479,P ＜0.05),MSaO2 (r =-0.519,P ＜ 0.05) was shown.There also revealed negative correlation between P3 amplitude and NREM Ⅰ and Ⅱ (r=-0.491,P ＜0.05),90％SaO2(r =-0.626,P＜0.01),AHI(r =-0.866,P ＜0.01),and positive correlation between P3 amplitude and NREM Ⅲ and Ⅳ (r =0.516,P ＜ 0.05),LSaO2 (r =0.475,P ＜ 0.05) 、MSaO2 (r =0.514,P ＜ 0.05).Stepwise regression and multivariate analysis revealed that AHI was one of the most significant influencing factors for latency and amplitude of P300 (P ＜ 0.01).Conclusion The OSAHS patients have cognitive dysfunction as reflected by the abnormalities of event-related potential P300 and the scale of its changes are correlated with the severity of OSAHS.The AHI is the most influential factor of P300.

The melanoma antigen (MAGE) family proteins are well known as tumor-specific antigens and comprise more than 60 genes, which share a conserved MAGE homology domain (MHD). Type I MAGEs are highly expressed cancer antigens, and they play an important role in tumorigenesis and cancer cell survival. Recently, several MAGE proteins were identified to interact with RING domain proteins, including a sub-family of E3 ubiquitin ligases. The binding mode between MAGEs and RING proteins was investigated and one important structure of these MAGE-RING complexes was solved: the MAGE-G1-NSE1 complex. Structural and biochemical studies indicated that MAGE proteins could adjust the E3 ubiquitin ligase activity of its cognate RING partner both in vitro and in vivo. However, the underlying mechanism was not fully understood. Here, we review these exciting advances in the studies on MAGE family, suggest potential mechanisms by which MAGEs activate the E3 activity of their binding RING proteins and highlight the anticancer potential of this family proteins.
Animals ; Humans ; Melanoma-Specific Antigens ; chemistry ; metabolism ; Protein Binding ; Protein Structure, Tertiary

TRPML1 channel is a non-selective group-2 transient receptor potential (TRP) channel with Ca permeability. Located mainly in late endosome and lysosome of all mammalian cell types, TRPML1 is indispensable in the processes of endocytosis, membrane trafficking, and lysosome biogenesis. Mutations of TRPML1 cause a severe lysosomal storage disorder called mucolipidosis type IV (MLIV). In the present study, we determined the cryo-electron microscopy (cryo-EM) structures of Mus musculus TRPML1 (mTRPML1) in lipid nanodiscs and Amphipols. Two distinct states of mTRPML1 in Amphipols are added to the closed state, on which could represent two different confirmations upon activation and regulation. The polycystin-mucolipin domain (PMD) may sense the luminal/extracellular stimuli and undergo a "move upward" motion during endocytosis, thus triggering the overall conformational change in TRPML1. Based on the structural comparisons, we propose TRPML1 is regulated by pH, Ca, and phosphoinositides in a combined manner so as to accommodate the dynamic endocytosis process.
Animals ; Calcium ; metabolism ; Cryoelectron Microscopy ; Endocytosis ; Endosomes ; metabolism ; Gene Expression ; HEK293 Cells ; Humans ; Hydrogen-Ion Concentration ; Lysosomes ; metabolism ; Mice ; Models, Biological ; Mucolipidoses ; genetics ; metabolism ; pathology ; Nanostructures ; chemistry ; ultrastructure ; Phosphatidylinositols ; metabolism ; Transgenes ; Transient Receptor Potential Channels ; chemistry ; genetics ; metabolism

Mechanosensitive (MS) channels are extensively studied membrane protein for maintaining intracellular homeostasis through translocating solutes and ions across the membrane, but its mechanisms of channel gating and ion selectivity are largely unknown. Here, we identified the YnaI channel as the Na/K cation-selective MS channel and solved its structure at 3.8 Å by cryo-EM single-particle method. YnaI exhibits low conductance among the family of MS channels in E. coli, and shares a similar overall heptamer structure fold with previously studied MscS channels. By combining structural based mutagenesis, quantum mechanical and electrophysiological characterizations, we revealed that ion selective filter formed by seven hydrophobic methionine (YnaI) in the transmembrane pore determined ion selectivity, and both ion selectivity and gating of YnaI channel were affected by accompanying anions in solution. Further quantum simulation and functional validation support that the distinct binding energies with various anions to YnaI facilitate Na/K pass through, which was defined as binding-block mechanism. Our structural and functional studies provided a new perspective for understanding the mechanism of how MS channels select ions driven by mechanical force.
Cryoelectron Microscopy ; Escherichia coli Proteins ; chemistry ; isolation & purification ; metabolism ; ultrastructure ; Ion Channels ; chemistry ; isolation & purification ; metabolism ; ultrastructure ; Mechanotransduction, Cellular ; Models, Molecular ; Quantum Theory

In the original publication the PDB numbers were not cited.