Deamidation accelerates amyloid formation and alters amylin fiber structure

Deamidation of asparagine and glutamine is the most common nonenzymatic, post-translational modification. Deamidation can influence the structure, stability, folding, and aggregation of proteins and has been proposed to play a role in amyloid formation. However there are no structural studies of the consequences of deamidation on amyloid fibers, in large part because of the difficulty of studying these materials using conventional methods. Here we examine the effects of deamidation on the kinetics of amyloid formation by amylin, the causative agent of type 2 diabetes. We find that deamidation accelerates amyloid formation and the deamidated material is able to seed amyloid formation by unmodified amylin. Using site-specific isotope labeling and two-dimensional infrared (2D IR) spectroscopy, we show that fibers formed by samples that contain deamidated polypeptide contain reduced amounts of β-sheet. Deamidation leads to disruption of the N-terminal β-sheet between Ala-8 and Ala-13, but β-sheet is still retained near Leu-16. The C-terminal sheet is disrupted near Leu-27. Analysis of potential sites of deamidation together with structural models of amylin fibers reveals that deamidation in the N-terminal β-sheet region may be the cause for the disruption of the fiber structure at both the N- and C-terminal β-sheet. Thus, deamidation is a post-translational modification that creates fibers that have an altered structure but can still act as a template for amylin aggregation. Deamidation is very difficult to detect with standard methods used to follow amyloid formation, but isotope-labeled IR spectroscopy provides a means for monitoring sample degradation and investigating the structural consequences of deamidation.     

Trusted Threat Intelligence Sharing in Practice and Performance Benchmarking through the Hyperledger Fabric Platform

Historically, threat information sharing has relied on manual modelling and centralised network systems, which can be inefficient, insecure, and prone to errors. Alternatively, private blockchains are now widely used to address these issues and improve overall organisational security. An organisation’s vulnerabilities to attacks might change over time. It is utterly important to find a balance among a current threat, the potential countermeasures, their consequences and costs, and the estimation of the overall risk that this provides to the organisation. For enhancing organisational security and automation, applying threat intelligence technology is critical for detecting, classifying, analysing, and sharing new cyberattack tactics. Trusted partner organisations can then share newly identified threats to improve their defensive capabilities against unknown attacks. On this basis, organisations can help reduce the risk of a cyberattack by providing access to past and current cybersecurity events through blockchain smart contracts and the Interplanetary File System (IPFS). The suggested combination of technologies can make organisational systems more reliable and secure, improving system automation and data quality. This paper outlines a privacy-preserving mechanism for threat information sharing in a trusted way. It proposes a reliable and secure architecture for data automation, quality, and traceability based on the Hyperledger Fabric private-permissioned distributed ledger technology and the MITRE ATT&CK threat intelligence framework. This methodology can also be applied to combat intellectual property theft and industrial espionage.     

探测到来自地幔的中微子

地球内部长寿命的放射性同位素的不断衰变对地球加热并发射出中微子。用大型探测器可以观测这些中微子。Borexino 合作组最近报道了一组新的关于这种“地球中微子”的数据,并指出,其中至少一些源自地幔。这项工作可以使研究人员更好地理解放射性衰变如何帮助驱动内部的地球物理过程,包括地幔中岩石的缓慢迁移。
中微子与物质的相互作用极其微弱。当中微子穿过1 光年厚的铅墙时,只有一半的中微子被阻止,所以,探测中微子是很具挑战性的。但是Borexino 和另一个国际合作组KamLAND 使用大型探测器曾以很高的置信度探测到地球中微子。研究人员希望通过更多的数据获得关于放射性同位素在地球内部的分布,以及它们释放给地下不同区域的热量分布的进一步信息。     

Investigations of a series of PPDI-based polyurethane block copolymers. II. Annealing effects

In a previous study, the morphologies of a group of paraphenylene diisocyanate (PPDI)-based polyurethane block copolymers were examined. These polyurethanes exhibited a multiphase structure with an interfacial boundary thickness estimated to be on the order of 1 nm and crystallization of the polyoxytetramethylene (POTM) flexible segment. Further studies involving annealing of these polyurethanes are reported here. An annealing time of 4 h was used, and the annealing temperature varied from 125 to 200°C. The samples have been characterized using differential scanning calorimetry (DSC) and with wide- and small-angle x-ray scattering (WAXS, SAXS) in order to determine the effects of annealing on the microphase structure. Annealing increases the phase separation of the two phases as evidenced by sharper endotherms in DSC thermograms and increased intensities in WAXS diffractometer traces. Annealing also slightly increases the transition zone thickness and long-period spacing. At the highest annealing temperature in this study, the long-period spacing increases dramatically due to hard segment domain aggregation.     

13C and 15N NMR spectra of 4-substituted-1-dimethylphosphonopiperazines

¹³C and ¹⁵N NMR chemical shifts and ¹³C-³¹P and ¹⁵N-³¹P coupling contants are reported for a series of ten 4-substituted-1-dimethylphosphonopiperazines.