Abstract:Extrasynaptic NMDA receptors, which locate in the extrasynaptic site rather than synaptic site have shown to mediate cell death pathway, while synaptic NMDA receptors play an important role in learning and memory and mediate cell survival pathway. This review discussed the reasons of their different distribution between synaptic and extrasynaptic sites, the different molecular mechanisms for signaling pathways of cell fate, as well as their roles in Alzheimer's disease (AD) based on the structure and function of NMDA receptors. Finally, we proposed a reasonable outlook on the treatment of AD from the view of extrasynaptic NMDA receptor.

Abstract:The dangerous signature came from unintegrated DNA or episome in cytoplasm could be detected by innate immunity, but how it works is unclear. Recently, more than 10 DNA sensors have been found to connect with the DNA sensing and immune defense. The cytosolic DNA induces the type Ⅰ interferon and other cytokines depended on the stimulator of interferon genes, namely STING (also known as ERIS, MITA, MPYS, and TMEM173), which functions as a key adaptor protein in the DNA sensing pathways. Surprisingly, some investigators identified a novel nucleotidyl transferase, cGAS, which produces an endogenous second-messenger cGAMP to activate STING in the cytoplasm of mammalian cells. However, how DNA activates STING to induce protective immune responses against virus, protozoa and bacteria need to be explored further. In this review, we discuss the recent research progress regarding the DNA sensing by cGAS and the mechanisms involved in activation of STING and subsequently immune responses.

Abstract:Recently, the new epigenetic marker, 5-hydroxymethylcytosine (5hmC) has been widely studied. 5hmC derived from the enzymatic oxidation of 5-methylcytosine (5mC) by TET(ten-eleven translocation) protein family and called as the "six base" of higher organism genomic DNA. It is found that 5hmC not only influence the structure and function of genome, but also play an important role during early embryonic development. This review mainly discussed the research advances of 5hmC in metabolic pathways, biological function, genome distribution and analysis methods.

Abstract:Glycation of nucleotides, proteins and phospholipids contributes to the development of late diabetic complications, including the most debilitating one——diabetic neuropathy. Reactive intermediates of AGE formation such as glyoxal, methylglyoxal (MG) and other dicarbonyls are detoxified by the glyoxalase-system. However little is known about the regulation and nature of the mechanisms underlying neuropathology. Therefore we decided to focus on the role of MG-glyoxalase 1 (GLO-1) system in modulation of painful diabetic neuropathy.

Abstract:Microsaccades are the largest and fastest of the fixational eye movements during attempted visual fixation. They can overcome visual fading that is due to neural adaptation and play an important role in the process of visual perception and cognition. We designed experiments to explore the difference of the microsaccades on the fixation tasks and attention tasks based on the correlation between microsaccades and visual perception. Comparing microsaccadic parameters in the different difficulty levels in fixation tasks, we found that amplitude, velocity and frequency of macaques' microsaccades are decreased with increasing task difficulty. On the other side, we don't get the same results on the two macaques on comparing the different visual tasks. It represents the different kind of visual tasks maybe lead to the different visual means. This conclusion will provide the basis for the further study on the mechanism of microsaccades.

Abstract:Kinesin-3 KIF1A is responsible for the anterograde transport of synapse vesicle (SV) precursors in axons. The CC1-FHA tandem of KIF1A has been revealed as a stable dimer that can trigger motor activity, but the mechanism underlying the regulation of the CC1-FHA dimer is unclear. Based on the CC1-FHA dimer structure, we found a potential phosphorylation motif "⁴⁸⁷SPKK⁴⁹⁰" located at the dimer interface. We demonstrated that the phosphorylation-mimetic mutation of Ser487 leads to the dissociation of the CC1-FHA dimer. Moreover, the Ser487-mutation could regulate the motor activity of KIF1A and the KIF1A-mediated axonal transport activity of SVs in C. elegans. Thus, the highly conserved "⁴⁸⁷SPKK⁴⁹⁰" motif may be a key site in the CC1-FHA tandem for regulating CC1-FHA dimerization and the subsequent activity of KIF1A.

Abstract:The notable features for inactivation of Ca_v3 channels are fast inactivating rate and strong voltage-dependence. We have investigated the molecular basis for determining the voltage-dependence of inactivation for Ca_v3.1, focusing on domain Ⅰ and Ⅱ. We made chimeras between Ca_v3.1 and Ca_v1.2. Chimeras were expressed in oocytes and currents were recorded by voltage clamp. For domain Ⅰ, replacement of S1～S4 or S5～S6 shifted the steady state inactivation curve significantly. These changes were mainly or partially caused by activation-inactivation coupling, rather than molecular modification. Replacement of domain Ⅱ shifted the inactivation curve significantly and these changes refer to molecular modification, indicating that domain Ⅱ contributed to the voltage-dependence of inactivation for Ca_v3.1. Furthermore, both voltage sensor region S1～S4 and pore region S5～S6 in domain Ⅱ were also involved, but Ⅰ-Ⅱ linker has no contribution. In addition, we found that the Ⅰ-Ⅱ linker and S5～S6 in domain Ⅰ contributed strongly to inactivation rate for Ca_v3.1, while S1～S4 in domain Ⅰ and Ⅱ was not involved. Taken collectively, our results suggest that domain Ⅱ plays a key role in determining the voltage-dependence of inactivation for Ca_v3.1, which was different from the molecular determinants for inactivating rate and for voltage-dependence of activation.

Abstract:FabB and FabF are two key long-chain 3-ketoacyl-ACP synthase in Escherichia coli. In addition to participating synthesis of long acyl chains, FabB is a key enzyme responsible for a condensation reaction in de novo unsaturated fatty acid synthesis and to form palmitoleoyl-ACP. While the FabF was found to be required for the elongation of cis-9-hexadecenoyl-ACP to cis-11-octadecenoyl-ACP and not involved in de novo unsaturated fatty acid synthesis. It has been reported previously that FabF homologues were found to have both KAS Ⅰ and Ⅱ activity just like FabB and FabF of E. coli in Enterococcus faecalis, Lactococcus lactis, Clostridium acetobutylicium and Ralstonia solanacearum. To test if this phenomenon is prevalent, we have carried out functional identification of five fabF homologous genes, Bacillus subtilis BsfabF, Sinorhizobium meliloti SmfabF, Vibrio cholera VcfabF, Pseudomonas aeruginosa PafabF1 and PafabF2. Our data revealed that five FabF homologues all have the long-chain 3-ketoacyl-ACP synthase activities in vitro. Analysis of phospholipid compositions show that SmfabF, VcfabF, PafabF1 and PafabF2 possessed 3-ketoacyl-ACP synthase Ⅱ (FabF) activity when complemented the E. coli fabF mutation CL28. The results of genetic complementation and thin-layer chromatographic analysis show that only PafabF2 gene could complement E. coli fabB mutation and PaFabF2 possessed partial function of 3-ketoacyl-ACP synthaseⅠ(FabB). These results demonstrated that not all FabF homologues have dual activity of KAS Ⅰ and KAS Ⅱ.

Abstract:Two dominant microalgae species in the East China Sea (ESC), Chaetoceros curvisetus(C. curvisetus) and Karenia mikimotoi (K. mikimotoi), were chosen to study the effects of temperature on microalga growth, nitrate reductase activity (NRA), and their relationship under laboratory set-up. At the beginning of the incubation, DIN, PO_{4-P, and SiO3-Si were added to 4 500 ml sea water in 5 L bottles to form a final concentration of 32 μmol/L, 1.5 μmol/L and 32 μmol/L, respectively. The bottles were then incubated under ambient sunlight(about 50 W·m^-2) at different temperatures (10℃, 15℃, 20℃, 25℃, and 30℃) for 10～20 days. Triplicates were employed for all treatments. The microalgae cell numbers were counted by hemacytometer counting method. S-logistic 2 population growth model was used to simulate microalgae growth , and calculate two growth-related parameters, the maximum growth rate (μmax) and the final biomass (Bf). The activity of nitrate reductase was measured in vitro and its relations to microalgal growth were elucidated. The two microalgae were observed to adapt to different temperature ranges. C. curvisetus could grow normally in the range of 10℃～30℃, while K. mikimotoionly grew well between 15℃～25℃. Both μmax and Bf reached the peak values at 20℃ for C. curvisetus and at 25℃ for K. mikimotoi, respectively. These results indicated that compared to C. curvisetus, K. mikimotoi had a relatively narrow range of suitable temperature and a high optimum temperature (Topt). Throughout the incubation time, NRA of the two species changed similarly under different temperatures. NRA raised slowly at the first 3～5 days, and then dropped rapidly. The maximum NRA values (NRAmax) usually occurred at the early exponential growth phase, prior to appearing time of μmax and Bf. The relations of μmax, NRAmax and Bf with temperature followed the Shelford tolerance law. All above results suggested that temperature could affect the nitrate assimilation ability of microalgae, and subsequently affect the growth of algae. μmax and the NRAmax per unit volume of the C. curvisetus were higher than those of K. mikimotoi under the same environmental conditions, indicating that C. curvisetus might have a better ability of absorbing and utilizing nitrate for self-growth than K. mikimotoi.}

Abstract:TAP2, tapasin and calreticulin (CRT) are three crucial components of the peptide loading complex (PLC) in MHC class Ⅰ antigen processing and presentation. While the functions of the proteins within the complex have been progressively defined, the hierarchical importance of the components has not been clearly and quantitatively analyzed. To compare the efficiency of MHC class Ⅰ antigen processing in different cell lines, we established a novel suilysin-mediated antigen delivery method to quantitatively analyze antigen processing in a number of cell lines, including K41, the CRT-deficient line K42, the tapasin-deficient line 90a and the tapasin/TAP2-deficient cell line 91a. We ranked the importance of the components of MHC class Ⅰ antigen processing such as CRT, TAP and tapasin using OVA challenge as the antigen model. Surprisingly, CRT was shown to be the most important component of the PLC, even though TAP was speculated to be the most crucial protein involved in the pathway. This is the first report that ranks the components of the antigen-processing pathway. Further investigation is required for elucidation of the roles played by the individual proteins within the complex.

Abstract:A new aptamer biosensor for detection of cTn I was established. It can detect cTn I in samples. The surface of GC was modified with anode-oxidation, amidation and activation modification. We used EDC and NHS as activators. Due to aptamer's specificity for cTn I, we can detect the concentration of cTn I in sample solution. The linear range of the analytical signal is observed from 0.05～5 nmol/L. The lowest detected concentration is 0.05 nmol/L. The detection time is 5 min.