Rapid FRET Assay for the Early Detection of Alpha-Synuclein Aggregation in Parkinson's Disease.

Alpha-synuclein (α-Syn) is a key protein of Parkinson's disease (PD). Oligomers formed by misfolding and aggregation of α-Syn can cause many pathological phenomena and aggravate the development of PD. Therefore, sensitive and accurate detection of oligomers is essential to understanding the pathology of PD and beneficial to screening and developing new drugs against PD. Here, we demonstrated a simple and sensitive method to detect the early aggregation of α-Syn via Förster resonance energy transfer (FRET) technology. We performed systematic investigations of the FRET sensitizations, efficiencies, and donor-to-acceptor distances during α-Syn aggregation, which was proved to be more sensitive to reflect small distance changes in the early stage of α-Syn aggregation, especially for α-Syn oligomers. The FRET assays were also applied to study the influence of Ser129 phosphorylation (pS129) on the aggregation rate of α-Syn. Our results showed that pS129 modification promotes α-Syn aggregation and enhances the ability of preformed fibrils to induce monomer aggregation. pS129 also increased the cytotoxicity of α-Syn. These results are of great significance for a better understanding of the pathological mechanisms of PD and future PD drug development.

Evolution-Based Discovery of Polyketide Acylated Valine from a Cytochalasin-Like Gene Cluster in Simplicillium lamelliciola HDN13430.

Utilizing a gene evolution-oriented approach for gene cluster mining, a cryptic cytochalasin-like gene cluster (sla) in Antarctic-derived Simplicillium lamelliciola HDN13430 was identified. Compared with the canonical cytochalasin biosynthetic gene clusters (BGCs), the sla gene cluster lacks the key α,ß-hydrolase gene. Heterologous expression of the sla gene cluster led to the discovery of a new compound, slamysin (1), characterized by an N-acylated amino acid structure and demonstrating weak anti-Bacillus cereus activity. These findings underscore the potential of genetic evolution in uncovering novel compounds and indicating specific adaptive evolution within specialized habitats.

A Study on the Bond-Slip Relationship of the CFRP-Steel Interface of CFRP Strengthened Steel.

The bonding interface between the CFRP and the steel plate is the weak link of CFRP-strengthened steel structures. This paper studies the bond-slip relationship of the CFRP-steel interface by experiments and numerical tests. First, a series of double-strap experiments on a CFRP-strengthened steel plate are carried out. The results show that the maximum shear stress of the bonding interface of the Q345B specimen is larger than that of the X100 specimen. The initial slip and maximum slip become larger as the thickness of the bonding interface becomes larger. Finite element analysis of the above tests is carried out; we introduce the maximum stress criterion to simulate the bonding interface, which assumes that when the nominal stress of the material reaches the maximum nominal stress of damage, the material begins to damage. The FE model established has proved very effective for analyzing the bond characteristics of CFRP-strengthened steel plates. Finally, a verification test was carried out, using an FE analysis to verify the accuracy of the modified equations; the results prove that the results of the modified equations are in good agreement with the numerical results and experiment results, which verifies the effectiveness of the equations.

Calcium protects bacteria against cadmium stress via reducing nitric oxide production and increasing iron acquisition.

Cadmium (Cd) is a common toxic heavy metal in the environment, and bacteria have evolved different strategies against Cd-toxicity. Here, we found that marine bacterium Bacillus sp. 98 could significantly alleviate Cd-toxicity by recruiting calcium (Ca) for reducing excessive intracellular nitric oxide (NO) and enhancing iron acquisition. To investigate the underlying mechanisms, mass spectrometry-based proteomic analysis was applied to Bacillus sp. 98 after treated with Cd supplemented with or without Ca. Compared with bacterial cells treated with Cd only, the proteomic results showed that the expression level of NO synthase was markedly down-regulated, while the expression levels of NO dioxygenase, which is responsible for converting NO to nitrate, and proteins associated with iron uptake were profoundly enhanced when Ca was supplemented. Consistently, bacterial intracellular NO amount was dramatically increased after Bacillus sp. 98 was treated with Cd, and reversed to a normal level when Ca or iron was supplemented. Notably, Ca also protected bacteria against stresses from other heavy metals including Cu, Cr, Mn, Ni and Zn, and this self-protection strategy was adopted as well in zebrafish, which encourages us to develop Ca-associated products against heavy metals toxicity in the future.

Comparison study on the performance of two different gas-permeable membranes used in a membrane-aerated biofilm reactor.

This study compared the performance of two different gas-permeable membranes, PVDF and PP membrane, in a membrane-aerated biofilm reactor (MABR). The surface characteristics and membrane pore blocking of these two membrane materials were studied utilizing AFM, SEM and CLSM. The PVDF membrane surface was more rough and hydrophilic, and possessed a better microbial affinity compared to PP. Furthermore, the MABR equipped with a PVDF membrane removed more COD (97.06 ±â€¯0.97%) and TN (85.66 ±â€¯0.87%) compared to the MABR with PP membrane (87.13 ±â€¯0.87% and 71.13 ±â€¯0.71%, respectively). As well, the PP membrane exhibited severe membrane pore blocking and had a lower oxygen transfer rate than the PVDF membrane. It is concluded that the PVDF membrane has potential as an aeration membrane material for MABRs.