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.     

胶莱盆地南部大盛群、王氏群的划分与对比

胶莱盆地在胶东半岛地质构造及造山带研究中占有重要地位,其巨厚的白垩系陆相沉积是石油系统多年的研究目标。胶莱盆地南部白垩纪的岩石地层序列较其北部更为复杂,其认识几经反复,其中尤以大盛群与王氏群和莱阳群的部分单位的关系为甚。本次工作通过详细对比其沉积层序、相互关系、古生物组合、岩石学特征及同位素年龄等因素,认为大盛群与王氏群属同一沉积层序,沉积基底相同、沉积环境相似、古生物群落时代一致,二者具有同时代、同沉积相、同岩石组合的一致性,应是一套地层,建议今后使用统一地层名称。     

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.     

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.     

共享交通的时空轨迹检索与群体发现

为解决共享交通下的共乘用户群体发现效率低、准确率不高问题，依据R-树原理建立GeoOD-Tree索引，并在此基础上提出以最大化共乘率为目标的群体发现策略。首先，对原始时空轨迹数据进行特征提取与标定处理，挖掘有效出行起讫点（OD）轨迹；其次，针对用户起讫点轨迹的特征，建立GeoOD-Tree索引进行有效的存储管理；最后，给出以最大化共乘行程为目标的群体发现模型，并运用K最近邻（KNN）查询对搜索空间剪枝压缩，提高群体发现效率。采用西安市近12000辆出租车营运轨迹数据，选取动态时间规整（DTW）等典型算法与所提算法在查询效率与准确率上进行性能对比分析。与DTW算法相比，所提算法的准确率提高了10.12%，查询效率提高了约15倍。实验结果表明提出的群体发现策略能有效提高共乘用户群体发现的准确率和效率，可有效提升共乘出行方式的出行率。     

澳门融入粤港澳大湾区世界机场群路向研究

粤港澳大湾区世界城市群与世界机场群相伴而生、联动发展.建设世界级机场群，需要5大机场错位发展和良性互动.澳门国际机场是澳门融入粤港澳大湾区重要一极，但机场发展存在与澳门定位、香港珠海空域空运矛盾、澳门土地和环境现状等相关的问题.因此，澳门国际机场今后发展需在葡语国家航线、珠澳密切合作、公务机产业方面努力实现跨越式发展.然而，澳门国际机场改扩建问题争议不断，本文就原址扩建、填海区新建、飞地黄茅岛新建3种模式进行比较分析，探索符合澳门长远利益之方案.     

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。