scholarly journals Design principles for the glycoprotein quality control pathway

2021 ◽  
Vol 17 (2) ◽  
pp. e1008654
Author(s):  
Aidan I. Brown ◽  
Elena F. Koslover

Newly-translated glycoproteins in the endoplasmic reticulum (ER) often undergo cycles of chaperone binding and release in order to assist in folding. Quality control is required to distinguish between proteins that have completed native folding, those that have yet to fold, and those that have misfolded. Using quantitative modeling, we explore how the design of the quality-control pathway modulates its efficiency. Our results show that an energy-consuming cyclic quality-control process, similar to the observed physiological system, outperforms alternative designs. The kinetic parameters that optimize the performance of this system drastically change with protein production levels, while remaining relatively insensitive to the protein folding rate. Adjusting only the degradation rate, while fixing other parameters, allows the pathway to adapt across a range of protein production levels, aligning with in vivo measurements that implicate the release of degradation-associated enzymes as a rapid-response system for perturbations in protein homeostasis. The quantitative models developed here elucidate design principles for effective glycoprotein quality control in the ER, improving our mechanistic understanding of a system crucial to maintaining cellular health.

2013 ◽  
Vol 288 (23) ◽  
pp. 16391-16402 ◽  
Author(s):  
Amit Kunte ◽  
Wei Zhang ◽  
Crina Paduraru ◽  
Natacha Veerapen ◽  
Liam R. Cox ◽  
...  

The non-classical major histocompatibility complex (MHC) homologue CD1d presents lipid antigens to innate-like lymphocytes called natural-killer T (NKT) cells. These cells, by virtue of their broad cytokine repertoire, shape innate and adaptive immune responses. Here, we have assessed the role of endoplasmic reticulum glycoprotein quality control in CD1d assembly and function, specifically the role of a key component of the quality control machinery, the enzyme UDP glucose glycoprotein glucosyltransferase (UGT1). We observe that in UGT1-deficient cells, CD1d associates prematurely with β2-microglobulin (β2m) and is able to rapidly exit the endoplasmic reticulum. At least some of these CD1d-β2m heterodimers are shorter-lived and can be rescued by provision of a defined exogenous antigen, α-galactosylceramide. Importantly, we show that in UGT1-deficient cells the CD1d-β2m heterodimers have altered antigenicity despite the fact that their cell surface levels are unchanged. We propose that UGT1 serves as a quality control checkpoint during CD1d assembly and further suggest that UGT1-mediated quality control can shape the lipid repertoire of newly synthesized CD1d. The quality control process may play a role in ensuring stability of exported CD1d-β2m complexes, in facilitating presentation of low abundance high affinity antigens, or in preventing deleterious responses to self lipids.


2017 ◽  
Vol 474 (18) ◽  
pp. 3179-3188 ◽  
Author(s):  
Chloe L. Stoyle ◽  
Paul E. Stephens ◽  
David P. Humphreys ◽  
Sam Heywood ◽  
Katharine Cain ◽  
...  

Rodent monoclonal antibodies with specificity towards important biological targets are developed for therapeutic use by a process of humanisation. This process involves the creation of molecules, which retain the specificity of the rodent antibody but contain predominantly human coding sequence. Here, we show that some humanised heavy chains (HCs) can fold, form dimers and be secreted even in the absence of a light chain (LC). Quality control of recombinant antibody assembly in vivo is thought to rely upon folding of the HC CH1 domain. This domain acts as a switch for secretion, only folding upon interaction with the LC CL domain. We show that the secreted heavy-chain dimers contain folded CH1 domains and contribute to the heterogeneity of antibody species secreted during the expression of therapeutic antibodies. This subversion of the normal quality control process is dependent on the HC variable domain, is prevalent with engineered antibodies and can occur when only the Fab fragments are expressed. This discovery will have an impact on the efficient production of both humanised antibodies and the design of novel antibody formats.


2021 ◽  
pp. 1-11
Author(s):  
Song Gang ◽  
Wang Xiaoming ◽  
Wu Junfeng ◽  
Li Shufang ◽  
Liu Zhuowen ◽  
...  

In view of the production quality management of filter rods in the manufacturing and execution process of cigarette enterprises, this paper analyzes the necessity of implementing the manufacturing execution system (MES) in the production process of filter rods. In this paper, the filter rod quality system of cigarette enterprise based on MES is fully studied, and the constructive information management system demand analysis, cigarette quality control process, system function module design, implementation and test effect are given. This paper utilizes the Fuzzy analytic hierarchy process to find the optimal system for processing the manufacturing of cigarette. The implementation of MSE based filter rod quality information management system for a cigarette enterprise ensures the quality control in the cigarette production process. Through visualization, real-time and dynamic way, the information management of cigarette production is completed, which greatly improves the quality of cigarette enterprise manufacturing process.


Cell ◽  
2021 ◽  
Vol 184 (11) ◽  
pp. 2896-2910.e13
Author(s):  
Haifeng Jiao ◽  
Dong Jiang ◽  
Xiaoyu Hu ◽  
Wanqing Du ◽  
Liangliang Ji ◽  
...  

2013 ◽  
Vol 141 (2) ◽  
pp. 798-808 ◽  
Author(s):  
Zhifang Xu ◽  
Yi Wang ◽  
Guangzhou Fan

Abstract The relatively smooth terrain embedded in the numerical model creates an elevation difference against the actual terrain, which in turn makes the quality control of 2-m temperature difficult when forecast or analysis fields are utilized in the process. In this paper, a two-stage quality control method is proposed to address the quality control of 2-m temperature, using biweight means and a progressive EOF analysis. The study is made to improve the quality control of the observed 2-m temperature collected by China and its neighboring areas, based on the 6-h T639 analysis from December 2009 to February 2010. Results show that the proposed two-stage quality control method can secure the needed quality control better, compared with a regular EOF quality control process. The new method is, in particular, able to remove the data that are dotted with consecutive errors but showing small fluctuations. Meanwhile, compared with the lapse rate of temperature method, the biweight mean method is able to remove the systematic bias generated by the model. It turns out that such methods make the distributions of observation increments (the difference between observation and background) more Gaussian-like, which ensures the data quality after the quality control.


PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0247925
Author(s):  
Pooi-Mun Wong ◽  
Shreya R. K. Sinha ◽  
Chee-Kong Chui

Blockchain has been applied to quality control in manufacturing, but the problems of false defect detections and lack of data transparency remain. This paper proposes a framework, Blockchain Quality Controller (BCQC), to overcome these limitations while fortifying data security. BCQC utilizes blockchain and Internet-of-Things to form a peer-to-peer supervision network. This paper also proposes a consensus algorithm, Quality Defect Tolerance (QDT), to adopt blockchain for during-production quality control. Simulation results show that BCQC enhances data security and improves defect detections. Although the time taken for the quality control process increases with the number of nodes in blockchain, the application of QDT allows multiple inspections on a workpiece to be consolidated at a faster pace, effectively speeding up the entire quality control process. The BCQC and QDT can improve the quality of parts produced for mass personalization manufacturing.


AGROINTEK ◽  
2019 ◽  
Vol 13 (1) ◽  
pp. 72
Author(s):  
Andan Linggar Rucitra ◽  
S Fadiah

<p><em>Telon oil is</em><em> one of </em><em> </em><em>the </em><em>traditional medicine in the form of </em><em> </em><em>liquid preparations that serves to provide a sense of warmth to the wearer. PT</em><em>.X</em><em> is one of the companies that produce</em><em> </em><em>telon</em><em> oil</em><em>.</em><em> To maintain</em><em> the quality of telon oil from PT.X</em><em> product</em><em>, required overall quality control that is starting from the quality control of raw materials, quality control process to the quality control of the final product. The purpose of this research is to know the application of Statistical Quality Control (SQC) in controlling the quality of telon oil in PT X. </em><em>F</em><em>inal product</em><em> quality</em><em> become one of the measurement of success of a process, so it needs a good quality control. SQC method used in this research is Pareto Diagram and Cause and Effect Diagram. Pareto diagram is a bar graph </em><em>that </em><em>show the problem based on the order of the number of occurrences of the most number of problems until the least happened. A causal diagram is often called a fishbone diagram, a tool for identifying potential causes of an effect or problem. The result of applying the method indicates that 80% defect is caused by unsuitable volume and on the incompatibility of Expired Date (ED) code. The damage is caused by several factors namely the method, labor, and machine while the most potential factor is the volume conformity to reduce the number of defect products.</em></p>


Author(s):  
A. V. Samonov ◽  
S. A. Sharov

The work looks at directions of developing regulatory and procedural and technological basis of weapons system software control and quality assurance processes. We present an improved software life cycle model and describe an automated technique of implementing a systemic end-to-end software quality control process.


2017 ◽  
Vol 5 (1) ◽  
pp. 35-42
Author(s):  
LIa Alfa Rosida ◽  
Sudiro Sudiro

The indicator achievement of minimum service standard (MSS) for the accuracy of distributingdrugs in Pharmacy Unit of Keluarga Sehat Hospital has not been achieved, even the incidence ofthe distributionerror from 2013 to 2016 continues to increase. The purpose of this researchwas to analyze the quality control process in the implementation of MSS in Pharmacy Unit of Keluarga Sehat Hospital. This was a qualitative research, with research subject 3pharmacy officers and 3 people of pharmacy management services.Data collectedby in-depth interview and observation of pharmaceutical performance report data and analysed by content analysis. The result of the research showed that the evaluation of pharmacy staff performance has not been implemented, because there is no performance appraisal indicator yet. Comparison was done only by comparing reports with general target, medical support manager double job resulted in no feedback to Pharmacy Unit, and so it has not supported the implementation of MSS. The Improvement of performancehas not been implementedand has notfound the concept of improvement. The new management will attempt to conduct a comparative study, including pharmacy installation into the Quality Control Group (GKM) or Problem Solving for Better Health (PSBH), find the cause of the problem and develop the policy. It can be concluded that the quality control of the MSS in the Pharmacy Unit still not going well and need to be improved especially related to quality performance appraisal and performance improvement based on the SOP.


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