scholarly journals Metabolite Damage and Damage-Control in a Minimal Genome

2021 ◽  
Author(s):  
Drago Haas ◽  
Antje M Thamm ◽  
Jiahi Sun ◽  
Lili Huang ◽  
Lijie Sun ◽  
...  
Keyword(s):  
Control Systems ◽  
Damage Control ◽  
Side Reactions ◽  
Enzymatic Reactions ◽  
Minimal Genome ◽  
The Core ◽  
Damage Repair ◽  
Nad Synthesis ◽  
Disulfide Reductase

Analysis of the genes retained in the minimized Mycoplasma JCVI-Syn3A genome established that systems that repair or preempt metabolite damage are essential to life. Several genes with known metabolite damage repair or preemption functions were identified and experimentally validated, including 5-formyltetrahydrofolate cyclo-ligase, CoA disulfide reductase, and certain hydrolases. Furthermore, we discovered that an enigmatic YqeK hydrolase domain fused to NadD has a novel proofreading function in NAD synthesis and could double as a MutT-like sanitizing enzyme for the nucleotide pool. Finally, we combined metabolomics and cheminformatics approaches to extend the core metabolic map of JCVI-Syn3A to include promiscuous enzymatic reactions and spontaneous side reactions. This extension revealed that several key metabolite damage-control systems remain to be identified in JCVI-Syn3A, such as that for methylglyoxal.

‘Nothing of chemistry disappears in biology’: the Top 30 damage-prone endogenous metabolites

2016 ◽  
Vol 44 (3) ◽  
pp. 961-971 ◽  
Author(s):  
Claudia Lerma-Ortiz ◽  
James G. Jeffryes ◽  
Arthur J.L. Cooper ◽  
Thomas D. Niehaus ◽  
Antje M.K. Thamm ◽  
...  
Keyword(s):  
Control Systems ◽  
Chemical Reactivity ◽  
Damage Control ◽  
Side Reactions ◽  
Predictive Tool ◽  
Metabolic Intermediates ◽  
Chemical Damage ◽  
Endogenous Metabolites ◽  
Genome Scale

Many common metabolites are intrinsically unstable and reactive, and hence prone to chemical (i.e. non-enzymatic) damage in vivo. Although this fact is widely recognized, the purely chemical side-reactions of metabolic intermediates can be surprisingly hard to track down in the literature and are often treated in an unprioritized case-by-case way. Moreover, spontaneous chemical side-reactions tend to be overshadowed today by side-reactions mediated by promiscuous (‘sloppy’) enzymes even though chemical damage to metabolites may be even more prevalent than damage from enzyme sloppiness, has similar outcomes, and is held in check by similar biochemical repair or pre-emption mechanisms. To address these limitations and imbalances, here we draw together and systematically integrate information from the (bio)chemical literature, from cheminformatics, and from genome-scale metabolic models to objectively define a ‘Top 30’ list of damage-prone metabolites. A foundational part of this process was to derive general reaction rules for the damage chemistries involved. The criteria for a ‘Top 30’ metabolite included predicted chemical reactivity, essentiality, and occurrence in diverse organisms. We also explain how the damage chemistry reaction rules (‘operators’) are implemented in the Chemical-Damage-MINE (CD-MINE) database (minedatabase.mcs.anl.gov/#/top30) to provide a predictive tool for many additional potential metabolite damage products. Lastly, we illustrate how defining a ‘Top 30’ list can drive genomics-enabled discovery of the enzymes of previously unrecognized damage-control systems, and how applying chemical damage reaction rules can help identify previously unknown peaks in metabolomics profiles.

scholarly journals Application of Artificial Intelligence Technology in Mechanical Electrical Control System

2021 ◽  
Vol 2066 (1) ◽  
pp. 012057
Author(s):  
Nan Li
Keyword(s):  
Artificial Intelligence ◽  
Control System ◽  
Control Systems ◽  
Current Status ◽  
Work Efficiency ◽  
Electrical Control ◽  
Existing Problems ◽  
The Core ◽  
Core Technology ◽  
Artificial Intelligence Technology

Abstract Artificial intelligence technology (A I T) has also been widely used in society. Combining A I T with mechanical and electrical control systems will bring huge profits to the corporate sector and greatly improve work efficiency. It can save a lot of money in the electrical control operations of all walks of life in the country, and fill the gap in this technology in the country. The purpose of this article is to study the application of A I T in mechanical electrical control systems (M E C S). This article first introduces the basic theories and concepts of A I T, extends the core technology of A I T, and combines the current status of the electrical control system of modern enterprises in our country to discuss its existing problems, and finally studies and analyzes A I T and machinery. Combination of electrical control systems, and discuss the application of A I T in mechanical electrical orifice subsystems. Experiments show that, compared with the existing M E C S, the M E C S using A I T can better complete the work and improve work efficiency.

scholarly journals Alternative methods of fuel consumption metering based on the on-board diagnostics outputs

2005 ◽  
Vol 53 (4) ◽  
pp. 23-32
Author(s):  
Jiří Čupera ◽  
Miroslav Havlíček
Keyword(s):  
Control Systems ◽  
Fuel Consumption ◽  
Government Regulation ◽  
Oxygen Sensor ◽  
Damage Control ◽  
Control Unit ◽  
Alternative Methods ◽  
Coolant Temperature ◽  
Torque Measurement

The article describes alternative methods of fuel consumption measurement based on model with using the diagnostic outputs of engine control unit. On-board diagnosis (the second level, known as OBD-2) has been mandated by government regulation because of advanced damage control systems in newer cars. However, its signals can be used for accurate analyses of power or torque measurement. On-board diagnostics offers many various parameters such a spark advance, intake air temperature, coolant temperature, throttle position, air flow mass and so on. Many of them have been unavailable without using sophisticated and expensive instrumentation. In the article are described two ways of fuel consumption measuring which are based on intake air consumption and knowledge about air-fuel ratio. First of them is founded on voltage output of oxygen sensor, the second on short (long) term fuel trim. As is shown at the end the second way gives more accurately results.

scholarly journals The discipline content design “Fundamentals of Automation and Telemechanics” for the sustainable development of competencies within the framework of educational programs

2021 ◽  
Vol 296 ◽  
pp. 08014
Author(s):  
Grigory Cherezov ◽  
Elena Rusakova ◽  
Vladimir Tselishchev
Keyword(s):  
Sustainable Development ◽  
Control Systems ◽  
Training Methods ◽  
The Sustainable Development ◽  
Train Control ◽  
The Core ◽  
Core Courses ◽  
Development Of Competencies ◽  
Different Content ◽  
Content Design

The trajectory generation is necessary to achieve sustainable development and the formation of the competencies of a specialist in the field of railway automation and telemechanics and communications. The trajectory is formed through studying the disciplines of the curriculum. The discipline structure is an important factor for the formation of competencies. The article studies the matters related to the discipline content design “Fundamentals of Automation and Telemechanics” for students in the specialty “Train Control Systems” of various specializations. It is shown that despite the fact that the discipline “Fundamentals of Automation and Telemechanics” belongs to the core courses of the educational program, for the sustainable development of the competencies of students of various specializations, it should have a different content. An exemplary discipline content for various specializations is proposed. The formed competences are presented. Along with possible training methods.

scholarly journals Impact of Flinch Technology on Damage Control and Survivability

2018 ◽  
Author(s):  
R Sahie-Pour ◽  
D Berenbaum
Keyword(s):  
Artificial Intelligence ◽  
Decision Making ◽  
Control System ◽  
Control Systems ◽  
Situational Awareness ◽  
Damage Control ◽  
Data Communication ◽  
Agent Based ◽  
Related Data ◽  
Data Communication Network

When a mission critical naval vessel is operating in dangerous waters or in battle, amongst other things, the success of its mission is a measure of capability and availability of its Weapon Systems, Combat and Communications Systems, Battle Damage Control System (BDCS) and Situational Awareness, as well as, its ability to recover from unplanned incidents. The next Generation Integrated Platform Management Systems (IPMS) for Autonomous Ships with much reduced manning, dictates special considerations for autonomous control systems across the ship support systems and beyond without need for man-in-the-loop for decision making. This entails detailed analysis, vulnerability and recoverability assessments during target ship’s basic design and the application of Artificial Intelligence (AI) where available. The optimum strategy involves consideration of distributed smart agent based control and monitoring systems that shall react rapidly to changes in operational demands and incidents without the need for man-in-the-loop, creating BDCS dynamic kill cards across ship subsystems and, extending the IPMS BDCS capabilities to Combat Management.  The above gives rise to consideration of “Flinch Technology (FT)” [7].  It implies distributed smart agent based control systems that instinctively reacts to incidents for fast recoverability in the event of damage to supervisory control system (i.e. IPMS) and its related data communication network. This paper addresses the benefits that might be gained as a result of consideration of  smart agent based control systems with no manin-the loop involvement for decision making. Such technology solutions, empowered by Artificial Intelligence (AI) could be adopted in the future Autonomous Combatant Ships. 

Massive Transfusion in a Child

2013 ◽  
Author(s):  
Stefan Sabato
Keyword(s):  
Direct Evidence ◽  
Massive Transfusion ◽  
Damage Control ◽  
Damage Control Surgery ◽  
Supporting Evidence ◽  
Damage Control Resuscitation ◽  
Acute Hemorrhage ◽  
Early Management ◽  
Major Morbidity ◽  
The Core

The traditional early management of hemorrhagic shock is currently being challenged, and many centers around the world have already changed their practice. Damage-control resuscitation, in conjunction with damage-control surgery, has been shown to improve major morbidity and mortality outcomes in adults. In children there is little direct evidence for these new approaches, but supporting evidence is accumulating. This chapter will introduce these concepts while also reinforcing the core principles of managing acute hemorrhage in the trauma setting.

scholarly journals The structure of the core NuRD repression complex provides insights into its interaction with chromatin

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Christopher J Millard ◽  
Niranjan Varma ◽  
Almutasem Saleh ◽  
Kyle Morris ◽  
Peter J Watson ◽  
...  
Keyword(s):  
Regulation Of Gene Expression ◽  
Order Structure ◽  
Histone H4 ◽  
Nurd Complex ◽  
Catalytic Core ◽  
The Core ◽  
Chaperone Protein ◽  
Damage Repair ◽  
Repression Complex ◽  
Carboxy Terminal

The NuRD complex is a multi-protein transcriptional corepressor that couples histone deacetylase and ATP-dependent chromatin remodelling activities. The complex regulates the higher-order structure of chromatin, and has important roles in the regulation of gene expression, DNA damage repair and cell differentiation. HDACs 1 and 2 are recruited by the MTA1 corepressor to form the catalytic core of the complex. The histone chaperone protein RBBP4, has previously been shown to bind to the carboxy-terminal tail of MTA1. We show that MTA1 recruits a second copy of RBBP4. The crystal structure reveals an extensive interface between MTA1 and RBBP4. An EM structure, supported by SAXS and crosslinking, reveals the architecture of the dimeric HDAC1:MTA1:RBBP4 assembly which forms the core of the NuRD complex. We find evidence that in this complex RBBP4 mediates interaction with histone H3 tails, but not histone H4, suggesting a mechanism for recruitment of the NuRD complex to chromatin.

scholarly journals Recent Research Progress in Taxol Biosynthetic Pathway and Acylation Reactions Mediated by Taxus Acyltransferases

Molecules ◽  
2021 ◽  
Vol 26 (10) ◽  
pp. 2855
Author(s):  
Tao Wang ◽  
Lingyu Li ◽  
Weibing Zhuang ◽  
Fengjiao Zhang ◽  
Xiaochun Shu ◽  
...  
Keyword(s):  
Biosynthetic Pathway ◽  
Structural Diversity ◽  
Underlying Mechanism ◽  
Research Progress ◽  
Enzymatic Reactions ◽  
Acylation Reaction ◽  
Taxol Biosynthesis ◽  
The Core ◽  
Coa Ligase ◽  
Acylation Reactions

Taxol is one of the most effective anticancer drugs in the world that is widely used in the treatments of breast, lung and ovarian cancer. The elucidation of the taxol biosynthetic pathway is the key to solve the problem of taxol supply. So far, the taxol biosynthetic pathway has been reported to require an estimated 20 steps of enzymatic reactions, and sixteen enzymes involved in the taxol pathway have been well characterized, including a novel taxane-10β-hydroxylase (T10βOH) and a newly putative β-phenylalanyl-CoA ligase (PCL). Moreover, the source and formation of the taxane core and the details of the downstream synthetic pathway have been basically depicted, while the modification of the core taxane skeleton has not been fully reported, mainly concerning the developments from diol intermediates to 2-debenzoyltaxane. The acylation reaction mediated by specialized Taxus BAHD family acyltransferases (ACTs) is recognized as one of the most important steps in the modification of core taxane skeleton that contribute to the increase of taxol yield. Recently, the influence of acylation on the functional and structural diversity of taxanes has also been continuously revealed. This review summarizes the latest research advances of the taxol biosynthetic pathway and systematically discusses the acylation reactions supported by Taxus ACTs. The underlying mechanism could improve the understanding of taxol biosynthesis, and provide a theoretical basis for the mass production of taxol.

scholarly journals Structure of the human SAGA coactivator complex

2021 ◽  
Author(s):  
Dominik A. Herbst ◽  
Meagan N. Esbin ◽  
Robert K. Louder ◽  
Claire Dugast-Darzacq ◽  
Gina M. Dailey ◽  
...  
Keyword(s):  
Chromatin Modification ◽  
Structural Elements ◽  
Saga Complex ◽  
Functional Elements ◽  
The Core ◽  
Damage Repair ◽  
Disease Mutations ◽  
Core Module ◽  
Important Therapeutic Target ◽  
Coactivator Complex

AbstractThe SAGA complex is a regulatory hub involved in gene regulation, chromatin modification, DNA damage repair and signaling. While structures of yeast SAGA (ySAGA) have been reported, there are noteworthy functional and compositional differences for this complex in metazoans. Here we present the cryogenic-electron microscopy (cryo-EM) structure of human SAGA (hSAGA) and show how the arrangement of distinct structural elements results in a globally divergent organization from that of yeast, with a different interface tethering the core module to the TRRAP subunit, resulting in a dramatically altered geometry of functional elements and with the integration of a metazoan-specific splicing module. Our hSAGA structure reveals the presence of an inositol hexakisphosphate (InsP6) binding site in TRRAP and an unusual property of its pseudo-(Ψ)PIKK. Finally, we map human disease mutations, thus providing the needed framework for structure-guided drug design of this important therapeutic target for human developmental diseases and cancer.

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