Role of the HSP70 Co-Chaperone SIL1 in Health and Disease

Cell surface and secreted proteins provide essential functions for multicellular life. They enter the endoplasmic reticulum (ER) lumen co-translationally, where they mature and fold into their complex three-dimensional structures. The ER is populated with a host of molecular chaperones, associated co-factors, and enzymes that assist and stabilize folded states. Together, they ensure that nascent proteins mature properly or, if this process fails, target them for degradation. BiP, the ER HSP70 chaperone, interacts with unfolded client proteins in a nucleotide-dependent manner, which is tightly regulated by eight DnaJ-type proteins and two nucleotide exchange factors (NEFs), SIL1 and GRP170. Loss of SIL1′s function is the leading cause of Marinesco-Sjögren syndrome (MSS), an autosomal recessive, multisystem disorder. The development of animal models has provided insights into SIL1′s functions and MSS-associated pathologies. This review provides an in-depth update on the current understanding of the molecular mechanisms underlying SIL1′s NEF activity and its role in maintaining ER homeostasis and normal physiology. A precise understanding of the underlying molecular mechanisms associated with the loss of SIL1 may allow for the development of new pharmacological approaches to treat MSS.     

Theoretical study on a kind of cyclization mechanism of boron trichloride and hexamethyldisilazane to form the borazine ring for SiBCN ceramics precursor

Borazine rings act as a pivotal part in siliconboroncarbonitride ceramics (SiBCN) for high-temperature stability and great resistance to crystallization. A detailed investigation of the ring formation mechanism will guide the design and synthesis of SiBCN to meet application requirements under extreme conditions. Boron trichloride (BCl₃) and hexamethyldisilazane (HN(SiMe₃)₂) are common raw materials for the synthesis of precursors for SiBCN. In this paper, quantum chemical calculation was used to study the cyclization reaction mechanism between BCl₃ and HN(SiMe₃)₂ to form trichloroborazine (TCBZ) at the MP2/6-31G (d,p) level of theory. We discussed the structure properties, reaction pathways, energy barriers, reaction rates, and other aspects in detail. The results show that BCl₃ and HN(SiMe₃)₂ alternately participate in the reaction process, accompanied by the release of trimethylchlorosilane (TMCS), and that the entire reaction shows an absolute advantage in terms of energy. In the Step by step reaction, lower reaction barriers are formed due to the introduction of BCl₃ with more heat released compared to that for the introduction of HN(SiMe₃)₂. The final single-molecule cyclization and TMCS elimination steps are found to be faster compared to all previous bimolecular reactions.     

A comparative study on hygroscopic and physiochemical properties of chicken powders obtained by different drying methods

Abstract

Different drying methods (spray drying (SD), vacuum drying (VD), microwave vacuum drying (MVD), and infrared vacuum drying (IFVD)) were applied in order to compare the hygroscopicity behavior of chicken powders. The hygroscopicity curves and glass transition temperature were used to evaluate the influence of ambient humidity and temperature on moisture absorption of powders. The results showed that the chicken powder dried by MVD had the lowest moisture absorption, followed by IFVD, VD, and SD. The hygroscopicity of SD chicken powders was different from other three kinds of chicken powders due to the physical properties of particles and the changes of protein secondary structure as detected by the Fourier transform-infrared spectrometer. For the three vacuum drying methods, the difference of protein secondary structure was the main reason of differences in hygroscopicity. Although MVD chicken powders were slightly inferior to SD chicken powders in taste, MVD chicken powders were the best in terms of smell and color as suggested by instrumental sensory parameter evaluations. It was found that MVD had a positive effect on reducing moisture absorption and maintaining sensory quality of chicken powders.     

Advancements in the Development of non-BET Bromodomain Chemical Probes

The bromodomain and extra terminal (BET) family of bromodomain-containing proteins (BCPs) have been the subject of extensive research over the past decade, resulting in a plethora of high-quality chemical probes for their tandem bromodomains. In turn, these chemical probes have helped reveal the profound biological role of the BET bromodomains and their role in disease, ultimately leading to a number of molecules in active clinical development. However, the BET subfamily represents just 8/61 of the known human bromodomains, and attention has now expanded to the biological role of the remaining 53 non-BET bromodomains. Rapid growth of this research area has been accompanied by a greater understanding of the requirements for an effective bromodomain chemical probe and has led to a number of new non-BET bromodomain chemical probes being developed. Advances since December 2015 are discussed, highlighting the strengths/caveats of each molecule, and the value they add toward validating the non-BET bromodomains as tractable therapeutic targets.     

Knowledge-Based Virtual Modeling and Simulation of Manufacturing Processes for Industry 4.0

Abstract

Industry 4.0 aims at providing a digital representation of a production landscape, but the challenges in building, maintaining, optimizing, and evolving digital models in inter-organizational production chains have not been identified yet in a systematic manner. In this paper, various Industry 4.0 research and technical challenges are addressed, and their present scenario is discussed. Moreover, in this article, the novel concept of developing experience-based virtual models of engineering entities, process, and the factory is presented. These models of production units, processes, and procedures are accomplished by virtual engineering object (VEO), virtual engineering process (VEP), and virtual engineering factory (VEF), using the knowledge representation technique of Decisional DNA. This blend of the virtual and physical domains permits monitoring of systems and analysis of data to foresee problems before they occur, develop new opportunities, prevent downtime, and even plan for the future by using simulations. Furthermore, the proposed virtual model concept not only has the capability of Query Processing and Data Integration for Industrial Data but also real-time visualization of data stream processing.     

Decomposition of first-order hybrid Petri nets for hierarchical control of manufacturing systems

Although hybrid Petri net (HPN) is a popular formalism in modelling hybrid production systems, the HPN model of large scale systems gets substantially complicated for analysis and control due to large dimensionality of such systems. To overcome this problem, a typical approach is to decompose the net into subnets and then control the plant through hierarchical or decentralized structures. Although this concept has been widely discussed in the literature for discrete PNs, there is a lack of research for HPNs. In this paper, a new method of decomposition of first-order hybrid Petri nets (FOHPNs) is proposed first and then the hierarchical control of the subnets through a coordinator is introduced. The advantage of using the proposed approach is validated by an existing example. A sugar milling case study is analysed by using a decomposed FOHPN model and the optimization results are compared against the results of the approaches presented in other papers. Simulation results show not only an improvement in production rate, but also show the ability to control the plant online. In addition, by using the hierarchical control structure for an FOHPN model, it is possible to reduce the cost of communication links, improve the reliability of the system, maintain the plant locally, and partially redesign the system.     

Chemical-Shift Perturbations Reflect Bile Acid Binding to Norovirus Coat Protein: Recognition Comes in Different Flavors

Bile acids have been reported as important cofactors promoting human and murine norovirus (NoV) infections in cell culture. The underlying mechanisms are not resolved. Through the use of chemical shift perturbation (CSP) NMR experiments, we identified a low-affinity bile acid binding site of a human GII.4 NoV strain. Long-timescale MD simulations reveal the formation of a ligand-accessible binding pocket of flexible shape, allowing the formation of stable viral coat protein–bile acid complexes in agreement with experimental CSP data. CSP NMR experiments also show that this mode of bile acid binding has a minor influence on the binding of histo-blood group antigens and vice versa. STD NMR experiments probing the binding of bile acids to virus-like particles of seven different strains suggest that low-affinity bile acid binding is a common feature of human NoV and should therefore be important for understanding the role of bile acids as cofactors in NoV infection.     

纳米氧化物对水泥基料化学收缩的影响

采用ASTM化学收缩试验方法,研究纳米SiO2、MgO、Al2O3对水泥基材料化学收缩变化的影响,明确纳米材料种类的差异性。结果表明,各实验组水泥基材料化学收缩均经历三阶段:急速变化区、缓慢变化区、平稳区,7d始水泥基材料化学收缩基本稳定。几种纳米材料的最佳掺量对水泥基材料的化学收缩改善作用大小为:SiO2>Al2O3>MgO。研究发现,纳米材料种类和掺量的不同对化学收缩的影响也较大,在选用时,需综合考虑。