No abstract

MicroRNAs are not widely studied in familial Alzheimer's disease cases, whether the microRNA profilings in familial Alzheimer's disease patients are similar to the sporadic AD patients is not known. This study aims to investigate the differential expression of microRNAs (miRNAs) associated with early-onset familial Alzheimer's disease (EO-FAD) in a Chinese family. We performed the gene mutation analysis in a family clinically diagnosed of EO-FAD. Micro-arrays were used to profile the miRNAs in cerebrospinal fluid of 2 affected members, 2 unaffected carriers and 2 mutation negative controls. The clinical presentation confirmed the EO-FAD diagnosis, and a recurrent mutation of the PSEN1 p.G378E was found in the family. The result showed that in the miRNAs expression profile, a total of 166 miRNAs were up-regulated and 3 miRNAs were down-regulated in the affected individuals compared with mutation negative individuals. But after Benjamini Hochberg FDR correction, only 25 miRNAs were significantly up-regulated and no miRNA was down-regulated, the levels of miR-30a-5p, miR-4758-3p and let-7a-3p were elevated significantly. Compared with mutation negative controls, 21 miRNAs were up-regulated and 18 microRNAs were down-regulated in the unaffected mutation carriers, after Benjamini Hochberg FDR correction, miR-345-5p was up-regulated and miR-4795-3p was down-regulated in the unaffected mutation carriers. And there was no difference between the affected members and unaffected mutation carriers. GO database showed that the top biological processes affected by the predicted target genes are nucleic acid binding transcription factor activity and transcription factor activity (sequence-specific DNA binding) (GO:0001071 and GO:0003700). The result of KEGG pathways showed 64 pathways were implicated in the regulatory network. The present study identified the miRNA profiling of Chinese siblings with G378E mutation in the PSEN1. Compared with mutation negative controls, the levels of 25 miRNAs including miR-30a-5p, miR-4758-3p and let-7a-3p were elevated significantly in the affected members, miR-345-5p was up-regulated and miR-4795-3p was down-regulated in the unaffected mutation carriers. Our study showed the microRNA profilings in the cases of a EO-FAD family with PSEN1 p.G378E mutation, but because of the individuals in the family was small, the results in other types of EO-FAD still need further studied.

Detection of hidden defects of aircraft long truss structures (aluminum alloy) is a challenging problem. The shape of the aircraft truss structure is complex, and the crack defects are buried in a large depth. Without the restriction of skin effect, remote field eddy current (RFEC) has great advantages in detecting buried depth defects. In this paper, in order to detect the hidden defects of the aluminum alloy aircraft long truss structure, the remote field eddy current probe is improved from two aspects of magnetic field enhancement and near-field signal suppression using the finite element method. The results show that indirect coupling energy is greatly enhanced when the connected magnetic circuit is added to the excitation coil. By adding a composite shielding structure outside the excitation coil and the detection coil, respectively, the direct coupling energy is effectively restrained. As a result, the size of the probe is reduced. By optimizing the coil spacing and probe placement position, the detection sensitivity of the probe is improved. The simulation is verified by experiments, and the experimental results are consistent with the simulation conclusions.

Background Phospholipase D (PLD) is highly valuable in the food and medicine industries, where it is used to convert low-cost phosphatidylcholine into high-value phospholipids (PLs). Despite being overexpressed in Streptomyces, PLD production requires expensive thiostrepton feeding during fermentation, limiting its industrialization. To address this issue, we propose a new thiostrepton-free system. Results We developed a system using a combinatorial strategy containing the constitutive promoter kasOp* and PLD G215S mutation fused to a signal peptide sigcin of Streptoverticillium cinnamoneum pld. To find a candidate vector, we first expressed PLD using the integrative vector pSET152 and then built three autonomously replicating vectors by substituting Streptomyces replicons to increase PLD expression. According to our findings, replicon 3 with stability gene (sta) inserted had an ideal result. The retention rate of the plasmid pOJ260-rep3-pld* was 99% after five passages under non-resistance conditions. In addition, the strain SK-3 harboring plasmid pOJ260-rep3-pld* produced 62 U/mL (3.48 mg/g) of PLD, which further improved to 86.8 U/mL (7.51 mg/g) at 32 °C in the optimized medium, which is the highest activity achieved in the PLD secretory expression to date. Conclusions This is the first time that a thiostrepton-free PLD production system has been reported in Streptomyces. The new system produced stable PLD secretion and lays the groundwork for the production of PLs from fermentation stock. Meanwhile, in the Streptomyces expression system, we present a highly promising solution for producing other complex proteins.

No abstract