Functions of ULK1 in autophagy and non-autophagy pathways and its implications in human physiology and disease

ULK1 (unc-51 like autophagy activating kinase 1), a mammalian serine/threonine kinase, is a key component of autophagy initiation complex and helps to induce all types of autophagy. Canonical autophagy is a process in which, through the interactions of a series of autophagy-related proteins, damaged organelles or misfolded proteins are engulfed by autophagosomes and then merged with lysosomes to be degraded. Thus, canonical autophagy is an important constituent part of the cellular “quality control.” Besides, accumulating evidence indicates that ULK1 exerts autophagy-independent effects in a cell-specific manner. For example, ULK1 facilitates neurite elongation through the regulation of endoplasmic reticulum (ER)–Golgi trafficking in neurons, stimulates phosphopentose pathway to help NADPH (nicotinamide adenine dinucleotide phosphate hydrogen) production, and acts as a duplex regulator in type I IFN (type I interferon) induced innate immune response. Considering the importance and diversity of ULK1 in various biological processes, this review aims to present a comprehensive overview of autophagy and non-autophagy related functions of ULK1 in a variety of human physiological, pathological, and disease processes.     

Analysis of Cerebrospinal Fluid Extracellular Vesicles by Proximity Extension Assay: A Comparative Study of Four Isolation Kits

There is a lack of reliable biomarkers for disorders of the central nervous system (CNS), and diagnostics still heavily rely on symptoms that are both subjective and difficult to quantify. The cerebrospinal fluid (CSF) is a promising source of biomarkers due to its close connection to the CNS. Extracellular vesicles are actively secreted by cells, and proteomic analysis of CSF extracellular vesicles (EVs) and their molecular composition likely reflects changes in the CNS to a higher extent compared with total CSF, especially in the case of neuroinflammation, which could increase blood–brain barrier permeability and cause an influx of plasma proteins into the CSF. We used proximity extension assay for proteomic analysis due to its high sensitivity. We believe that this methodology could be useful for de novo biomarker discovery for several CNS diseases. We compared four commercially available kits for EV isolation: MagCapture and ExoIntact (based on magnetic beads), EVSecond L70 (size-exclusion chromatography), and exoEasy (membrane affinity). The isolated EVs were characterized by nanoparticle tracking analysis, ELISA (CD63, CD81 and albumin), and proximity extension assay (PEA) using two different panels, each consisting of 92 markers. The exoEasy samples did not pass the built-in quality controls and were excluded from downstream analysis. The number of detectable proteins in the ExoIntact samples was considerably higher (~150% for the cardiovascular III panel and ~320% for the cell regulation panel) compared with other groups. ExoIntact also showed the highest intersample correlation with an average Pearson’s correlation coefficient of 0.991 compared with 0.985 and 0.927 for MagCapture and EVSecond, respectively. The median coefficient of variation was 5%, 8%, and 22% for ExoIntact, MagCapture, and EVSecond, respectively. Comparing total CSF and ExoIntact samples revealed 70 differentially expressed proteins in the cardiovascular III panel and 17 in the cell regulation panel. To our knowledge, this is the first time that CSF EVs were analyzed by PEA. In conclusion, analysis of CSF EVs by PEA is feasible, and different isolation kits give distinct results, with ExoIntact showing the highest number of identified proteins with the lowest variability.     

伸缩桥板的开发与实践

本文就伸缩桥板产品的开发及生产实践中存在的问题进行了分析，挖掘了产品开发与生产转化的关系。     

数字电视用中分辨率74cm纯平彩色显像管BC配列不良的分析与对策

通过对74cm中分辨率纯平彩色显像管BC配列局部严重群散不良的调查分析,确定荫罩受力塌陷是主要原因,通过改良设计、工艺优化及其它方面的综合对策,使以上技术难题得到满意的解决,整管不良率由4.78%下降到0.172%。     

RFID电子门票解决方案(三)

继第二、三期的专题连载(一)和(二)之后,这次介绍门票系统的扩展和系统的优势,并且给出了各种门票的对比表。     

可拓知识空间和可拓知识网格模型(Ⅱ):可拓知识网格

第1部分中已介绍了可拓知识空间定义和相关操作，以及可拓知识空间关联函数计算方法。这一部分进一步建立可拓知识空间语义网、可拓知识网格和可拓知识网格服务，并给出实例和相关的分析讨论。     

可拓检测的方案生成

以可拓学理论为基础，论述了可拓检测的有关定义和概念，提出了可拓检测的方案生成方法及过程，同时探讨了检测方法的优化和评价方法。     

含盐不均匀基底变形对盖层构造的影响

根据相似性原理，选择不同的相似材料模拟双侧挤压作用下含盐不均匀基底变形对盖层构造的影响。实验表明：（1）双侧挤压背景下，受硬泡沫和凡士林代表的不同性质的基底的影响，上覆细沙盖层中形成的构造样式不同；（2）尽管模型的基底结构左右两侧基本对称，但上覆盖层的变形样式并不完全对称；（3）变形后期，盐脊顶部上覆沙层出现明显的塌陷构造；（4）实验最终结果显示的整个背冲构造的形成是由两个分割开的次级构造逐步合并而成的。     

谈地下室工程的防水

就地下室工程的防水,从设计、混凝土自防水、附加防水层的设置及各种附加防水层的分析与比较、多道设防综合治理、系统防水等方面,笔者提出了自己的见解或建议。     

缺省理论的简化

缺省理论△=(D,W)中的缺省规则集D,是该理论的不确定因素.如果能去掉一些缺省规则而又不影响该理论的延伸,则就在一定程度上简化了该理论.本文证明了关于规范缺省理论的延伸的若干性质,利用这些性质,我们可以把某些规范缺省理论在一定条件下得以化简,有的甚至可以把它们化为一阶逻辑理论.