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.     

Predicting Prostephanus truncatus (Horn) (Coleoptera: Bostrichidae) populations and associated grain damage in smallholder farmers’ maize stores: A machine learning approach

Prostephanus truncatus is a notorious pest of stored-maize grain and its spread throughout sub-Saharan Africa has led to increased levels of grain storage losses. The current study developed models to predict the level of P. truncatus infestation and associated damage of maize grain in smallholder farmer stores. Data were gathered from grain storage trials conducted in Hwedza and Mbire districts of Zimbabwe and correlated with weather data for each site. Insect counts of P. truncatus and other common stored grain insect pests had a strong correlation with time of year with highest recorded numbers from January to May. Correlation analysis showed insect-generated grain dust from boring and feeding activity to be the best indicator of P. truncatus presence in stores (r = 0.70), while a moderate correlation (r = 0.48) was found between P. truncatus numbers and storage insect parasitic wasps, and grain damage levels significantly correlated with the presence of Tribolium castaneum (r = 0.60). Models were developed for predicting P. truncatus infestation and grain damage using parameter selection algorithms and decision-tree machine learning algorithms with 10-fold cross-validation. The P. truncatus population size prediction model performance was weak (r = 0.43) due to the complicated sampling and detection of the pest and eight-week long period between sampling events. The grain damage prediction model had a stronger correlation coefficient (r = 0.93) and is a good estimator for in situ stored grain insect damage. The models were developed for use under southern African climatic conditions and can be improved with more input data to create more precise models for building decision-support tools for smallholder maize-based production systems.     

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.     

基于梯度提升决策树的车轮轮缘厚度磨耗预测

轮对在列车走行过程中起着导向、承受以及传递载荷的作用，其踏面及轮缘磨耗对地铁列车运行安全性和钢轨的寿命都将产生重要影响。根据地铁列车车轮磨耗机理，分析车轮尺寸数据特点，针对轮缘厚度这一型面参数，基于梯度提升决策树算法构建轮缘厚度磨耗预测模型。在该模型的基础上，任意选取某轮对数据进行验证分析，结果表明：基于梯度提升决策树的轮对磨耗预测模型具有较好的预测精度，可预测出1~6个月的轮缘厚度变化趋势范围，预测时间范围较长，可为地铁维保部门对轮对的维修方式由状态修转为预防修提供指导性建议。     

Mathematical representation of radiality constraint in distribution system reconfiguration problem

Distribution systems are most commonly operated in a radial configuration for a number of reasons. In order to impose radiality constraint in the optimal network reconfiguration problem, an efficient algorithm is introduced in this paper based on graph theory. The paper shows that the normally followed methods of imposing radiality constraint within a mixed-integer programming formulation of the reconfiguration problem may not be sufficient. The minimum-loss network reconfiguration problem is formulated using different ways to impose radiality constraint. It is shown, through simulations, that the formulated problem using the proposed method for representing radiality constraint can be solved more efficiently, as opposed to the previously proposed formulations. This results in up to 30% reduction in CPU time for the test systems used in this study.     

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.     

绿色化工技术在精细化工中的应用研究

社会经济快速发展,科学技术不断进步,针对我国现代工业化工行业发展,所产生的新型化工技术应用,促进我国化工生产效率的提升。工业的发展不可避免地会带来污染物的产生,如果不能有效控制化工排放污染物,温室效应问题会更加严重。本文对绿色化工技术在精细化工中的有效应用进行研究,降低工业废气污染物排放量,维护生态环境平衡。