scholarly journals Biocatalytic Formation of Novel Polyesters with para-Hydroxyphenyl groups in the Backbone - Engineering Cupriavidus necator for production of high-performance materials from CO2 and electricity

2021 ◽  
Author(s):  
Nils Jonathan Helmuth Averesch ◽  
Vincent Evan Pane ◽  
Frauke Kracke ◽  
Marika Ziesack ◽  
Shannon Noel Nangle ◽  
...  
Keyword(s):  
High Performance ◽  
Durable Goods ◽  
De Novo ◽  
Cupriavidus Necator ◽  
Pha Synthase ◽  
Mode Analysis ◽  
Modern World ◽  
Knock Out ◽  
Cell Factories ◽  
Aromatic Polyesters

Synthetic materials are integral components of consumables and durable goods and indispensable in our modern world. Polyesters are the most versatile bulk- and specialty-polymers, but their production is not sustainable, and their fate at end-of-life of great concern. Bioplastics are highly regarded alternatives but have shortcomings in material properties and commercial competitiveness with conventional synthetic plastics. These constraints have limited the success in global markets. Enabling bio-production of advanced bioplastics with superior properties from waste-derived feedstocks could change this. We have created microbial cell factories that can produce a range of aliphatic and aromatic polyesters. A DphaC1 mutant of Cupriavidus necator H16 was complemented with hydroxyacyl-CoA transferases from either Clostridium propionicum (pct540) or Clostridium difficile (hadA), respectively. These were combined with a mutant PHA synthase (phaC1437) from Pseudomonas sp. MBEL 6 19, which rescued the PHA- phenotype of the knock-out mutant and allowed polymerization of various hydroxy carboxylates, including phloretic acid. This is the first-time, incorporation of an aromatic ring in the backbone of a biological polyester was achieved. Polymers contain para-hydroxyphenyl subunits are structurally analogous to synthetic aromatic polyesters like PET and high-strength polyarylates. In a further advance, the transgenic strain was cultivated in a bio-electrochemical system under autotrophic conditions, enabling synthesis of aromatic bio-polyesters from H2 and O2 generated in situ, while assimilating CO2. Follow-up elementary flux-mode analysis established the feasibility of de novo production of twenty different polyesters from five different carbon- and energy-sources. This comprehensive study opens the door to sustainable bio-production of high-performance thermoplastics and thermosets.

Direct carbon capture for production of high-performance biodegradable plastic by cyanobacterial cell factory

2021 ◽  
Author(s):  
Chunlin Tan ◽  
Fei Tao ◽  
Ping Xu
Keyword(s):  
Metabolic Engineering ◽  
Carbon Capture ◽  
De Novo ◽  
Pha Synthase ◽  
Cell Factory ◽  
Cyanobacterial Cell ◽  
Plastic Pollution ◽  
Cell Factories ◽  
Coa Transferase ◽  
Dry Cell Weight

Plastic pollution has become one of the most pressing environmental issues today, leading to an urgent need to develop biodegradable plastics1-3. Polylactic acid (PLA) is one of the most promising biodegradable materials because of its potential applications in disposable packaging, agriculture, medicine, and printing filaments for 3D printers4-6. However, current biosynthesis of PLA entirely uses edible biomass as feedstock, which leads to competition for resources between material production and food supply7,8. Meanwhile, excessive emission of CO2 that is the most abundant carbon source aggravates global warming, and climate instability. Herein, we first developed a cyanobacterial cell factory for the de novo biosynthesis of PLA directly from CO2, using a combinational strategy of metabolic engineering and high-density cultivation (HDC). Firstly, the heterologous pathway for PLA production, which involves engineered D-lactic dehydrogenase (LDH), propionate CoA-transferase (PCT), and polyhydroxyalkanoate (PHA) synthase, was introduced into Synechococcus elongatus PCC7942. Subsequently, different metabolic engineering strategies, including pathway debottlenecking, acetyl-CoA self-circulation, and carbon-flux redirection, were systematically applied, resulting in approximately 19-fold increase to 15 mg/g dry cell weight (DCW) PLA compared to the control. In addition, HDC increased cell density by 10-fold. Finally, the PLA titer of 108 mg/L (corresponding to 23 mg/g DCW) was obtained, approximately 270 times higher than that obtained from the initially constructed strain. Moreover, molecular weight (Mw, 62.5 kDa; Mn, 32.8 kDa) of PLA produced by this strategy was among the highest reported levels. This study sheds a bright light on the prospects of plastic production from CO2 using cyanobacterial cell factories.

TAMI-37. STEAROYL-COA DESATURASE 1 IS ESSENTIAL FOR THE GROWTH OF IDH MUTANT GLIOMA

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi206-vi206
Author(s):  
Tomohiro Yamasaki ◽  
Lumin Zhang ◽  
Tyrone Dowdy ◽  
Adrian Lita ◽  
Mark Gilbert ◽  
...  
Keyword(s):  
Glioma Cell ◽  
De Novo ◽  
Glioma Cells ◽  
Model Systems ◽  
De Novo Lipogenesis ◽  
Wild Type ◽  
Knock Out ◽  
Stearoyl Coa Desaturase ◽  
Scd1 Expression

Abstract BACKGROUND Increased de novo lipogenesis is a hallmark of cancer metabolism. In this study, we interrogated the role of de novo lipogenesis in IDH1 mutated glioma’s growth and identified the key enzyme, Stearoyl-CoA desaturase 1 (SCD1) that provides this growth advantage. MATERIALS ANDMETHODS We prepared genetically engineered glioma cell lines (U251 wild-type: U251WT and U251 IDHR132H mutant: U251RH) and normal human astrocytes (empty vector induced-NHA: NHAEV and IDHR132H mutant: NHARH). Lipid metabolic analysis was conducted by using LC-MS and Raman imaging microscopy. SCD1 expression was investigated by The Cancer Genome Atlas (TCGA) data analysis and Western-blotting method. Knock-out of SCD1 was conducted by using CRISPR/Cas9 and shRNA. RESULTS Previously, we showed that IDH1 mut glioma cells have increased monounsaturated fatty acids (MUFAs). TCGA data revealed IDH mut glioma shows significantly higher SCD1 mRNA expression than wild-type glioma. Our model systems of IDH1 mut (U251RH, NHARH) showed increased expression of this enzyme compared with their wild-type counterpart. Moreover, addition of D-2HG to U251WT increased SCD1 expression. Herein, we showed that inhibition of SCD1 with CAY10566 decreased relative cell number and sphere forming capacity in a dose-dependent manner. Furthermore, addition of MUFAs were able to rescue the SCD1 inhibitor induced-cell death and sphere forming capacity. Knock out of SCD1 revealed decreased cell proliferation and sphere forming ability. Decreasing lipid content from the media did not alter the growth of these cells, suggesting that glioma cells rely on de novo lipid synthesis rather than scavenging them from the microenvironment. CONCLUSION Overexpression of IDH mutant gene altered lipid composition in U251 cells to enrich MUFA levels and we confirmed that D-2HG caused SCD1 upregulation in U251WT. We demonstrated the glioma cell growth requires SCD1 expression and the results of the present study may provide novel insights into the role of SCD1 in IDH mut gliomas growth.

scholarly journals Changing Trends in Computer Architecture : A Comprehensive Analysis of ARM and x86 Processors

2021 ◽  
pp. 619-631
Author(s):  
Khushi Gupta ◽  
Tushar Sharma
Keyword(s):  
Computer Architecture ◽  
High Performance ◽  
Comprehensive Analysis ◽  
Low Power Consumption ◽  
Modern World ◽  
Development Environment ◽  
Processor Architectures ◽  
Software Development Environment ◽  
Changing Trends ◽  
Microprocessor Industry

In the modern world, we use microprocessors which are either based on ARM or x86 architecture which are the most common processor architectures. ARM originally stood for ‘Acorn RISC Machines’ but over the years changed to ‘Advanced RISC Machines’. It was started as just an experiment but showed promising results and now it is omnipresent in our modern devices. Unlike x86 which is designed for high performance, ARM focuses on low power consumption with considerable performance. Because of the advancements in the ARM technology, they are becoming more powerful than their x86 counterparts. In this analysis we will collate the two architectures briefly and conclude which microprocessor will dominate the microprocessor industry. The processor which will perform better in different tests will be more suitable for the reader to use in their application. The shift in the industry towards ARM processors can change how we write softwares which in turn will affect the whole software development environment.

scholarly journals CLOUD TECHNOLOGIES IN BUSINESS MANAGEMENT

2021 ◽  
Vol 4 (39) ◽  
pp. 294-301
Author(s):  
V. Gevko ◽  
O. Vivchar ◽  
V. Sharko ◽  
О. Radchenko ◽  
M. Budiaiev ◽  
...  
Keyword(s):  
Business Processes ◽  
Service Providers ◽  
De Novo ◽  
Cloud Service ◽  
Jel Classification ◽  
Digital Transformation ◽  
Cloud Services ◽  
Modern World ◽  
High Tech ◽  
Cloud Technologies

Abstract. The modern world is in the phase of active implementation of digitalization of most processes, including cloud technologies, which is also associated with the introduction of quarantine measures in most countries. Over the past decade, the average annual growth of the cloud services market has expanded by about 50% to more than $ 220 billion. This figure is projected to exceed $ 500 billion in the near future. Currently, a large number of cloud service companies are concentrated in the market. All companies can be classified into national, operating within one country, and international, operating in many countries simultaneously. In Ukraine, the leader is the high-tech company De Novo, which provides services in the segment of corporate clients based on VMware, EMC, Microsoft Azure solutions. Competitors are well-known foreign IT giants, namely: Oracle, IBM, Google, Microsoft, Amazon, HP and others. The Ministry of Digital Transformation of Ukraine plays an important role in this area. The latter signed an agreement with Microsoft to implement the Azure Expansion Program and accelerate Ukraine's digital transformation, including the development of Azure cloud services for the sum of more than $ 500 million. The transition from physical, outdated IT technologies to new cloud services will allow companies to significantly reduce the cost of maintaining their own staff of IT professionals and engineers, reduce dependence on IT equipment suppliers and increase productivity and efficiency of the decisions made. The management of the enterprise can choose one of the offered models from the companies-providers: IaaS, PaaS, SaaS. The choice will depend on the immediate management needs and financial capabilities of the enterprise. In Ukraine, the biggest share of users of cloud services belongs to large utility companies and state enterprises, namely: Dija, Ministry of Internal Affairs, Kyiv Municipal Enterprise "Informatics", Prozorro, Ukrposhta, E-Health (National Health Center of Ukraine), Naftogaz and several other organizations. Thus, the introduction of cloud services involves digital business transformations, namely: optimization of business processes, acceleration of innovation, cost reduction and so on. Key words: IT technologies, cloud technologies, cloud service providers, management, business. JEL Classification L86, M15 Formulas: 0; fig.: 1; tabl.: 2; bibl.: 21.

scholarly journals A parallel computational framework for ultra-large-scale sequence clustering analysis

2018 ◽  
Vol 35 (3) ◽  
pp. 380-388 ◽  
Author(s):  
Wei Zheng ◽  
Qi Mao ◽  
Robert J Genco ◽  
Jean Wactawski-Wende ◽  
Michael Buck ◽  
...  
Keyword(s):  
Parallel Computing ◽  
High Performance ◽  
Large Scale ◽  
De Novo ◽  
Rapid Development ◽  
Operational Taxonomic Unit ◽  
Supplementary Information ◽  
Computational Framework ◽  
Speed Up ◽  
Scale Sequence

Abstract Motivation The rapid development of sequencing technology has led to an explosive accumulation of genomic data. Clustering is often the first step to be performed in sequence analysis. However, existing methods scale poorly with respect to the unprecedented growth of input data size. As high-performance computing systems are becoming widely accessible, it is highly desired that a clustering method can easily scale to handle large-scale sequence datasets by leveraging the power of parallel computing. Results In this paper, we introduce SLAD (Separation via Landmark-based Active Divisive clustering), a generic computational framework that can be used to parallelize various de novo operational taxonomic unit (OTU) picking methods and comes with theoretical guarantees on both accuracy and efficiency. The proposed framework was implemented on Apache Spark, which allows for easy and efficient utilization of parallel computing resources. Experiments performed on various datasets demonstrated that SLAD can significantly speed up a number of popular de novo OTU picking methods and meanwhile maintains the same level of accuracy. In particular, the experiment on the Earth Microbiome Project dataset (∼2.2B reads, 437 GB) demonstrated the excellent scalability of the proposed method. Availability and implementation Open-source software for the proposed method is freely available at https://www.acsu.buffalo.edu/~yijunsun/lab/SLAD.html. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals Fast Depth Intra Mode Decision Based on Mode Analysis in 3D Video Coding

Electronics ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 430 ◽  
Author(s):  
Jin Young Lee
Keyword(s):  
Video Coding ◽  
High Performance ◽  
Depth Map ◽  
3D Video ◽  
Mode Decision ◽  
Mode Analysis ◽  
Multiview Video ◽  
3D Video Coding ◽  
Depth Coding ◽  
Intra Mode Decision

Multiview video plus depth (MVD), which consists of a texture image and its associated depth map, has been introduced as a 3D video format, and 3D video coding, such as 3D-HEVC, was developed to efficiently compress this MVD data. However, this requires high encoding complexity because of the additional depth coding. In particular, intra coding using various prediction modes is very complicated. To reduce the complexity, we propose a fast depth intra mode decision method based on mode analysis. The proposed method adaptively reduces the number of original candidate modes in a mode decision process. Experimental results show that the proposed method achieves high performance in terms of the complexity reduction.

Endothelin synthesis by rabbit renal tubule cells

1991 ◽  
Vol 261 (2) ◽  
pp. F221-F226 ◽  
Author(s):  
D. E. Kohan
Keyword(s):  
High Performance ◽  
Renal Tubule ◽  
De Novo ◽  
Collecting Duct ◽  
Cell Types ◽  
Phospholipid Metabolism ◽  
Thick Ascending Limb ◽  
Medullary Collecting Duct ◽  
Tubule Cells ◽  
Endothelin 3

Endothelins regulate nephron sodium and water transport, prostaglandin E2 (PGE2) synthesis, and phospholipid metabolism. Recent studies suggest that renal tubule cells synthesize endothelins. To determine which nephron sites have such potential, endothelin production by cells derived from different nephron segments was examined. Immunoreactive endothelin 1 (ET-1) and endothelin 3 (ET-3) were measured in supernatants of cultured rabbit proximal tubule (PT), medullary thick ascending limb (MTAL), cortical collecting tubule (CCT), and inner medullary collecting duct (IMCD) cells. All cell types released immunoreactive ET-1 and ET-3. However, the amounts of endothelin produced differed as follows: IMCD greater than MTAL greater than CCT much greater than PT for ET-1 and IMCD greater than MTAL = PT = CCT for ET-3; in all cases ET-1 much greater than ET-3. To confirm de novo ET-3 synthesis, IMCD cells were labeled with [35S]cysteine, and the supernatant was immunoprecipitated with anti-ET-3 antibody. Sample and standard ET-3 eluted at identical positions on high-performance liquid chromatographs, confirming de novo synthesis of ET-3 by cultured IMCD cells. These data raise the possibility of an important functional role for nephron-derived endothelin and, in particular, endothelin produced by tubule cells in the medulla.

Mutations in the AML1 Gene Define an Unfavorable Subgroup in Acute Myeloid Leukemia with FAB M0.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4340-4340
Author(s):  
Frank Dicker ◽  
Mirjam Klaus ◽  
Torsten Haferlach ◽  
Wolfgang Kern ◽  
Wolfgang Hiddemann ◽  
...  
Keyword(s):  
High Performance ◽  
De Novo ◽  
Mutation Screening ◽  
Point Mutations ◽  
Gene Mutations ◽  
Normal Karyotype ◽  
Runt Domain ◽  
Screening Efficiency ◽  
Genetic Aberration ◽  
Aml1 Gene

Abstract The AML1/RUNX1 gene is the most frequent target for chromosomal translocations in leukemia. Recently point mutations in the AML1 gene have been demonstrated as another mode of genetic aberration. AML1 mutations have been reported in de novo MDS and AML, as well as in therapy related MDS and AML. The AML M0 subtype has been found to be most frequently affected by sporadic AML1 gene mutations. We analysed AML1 gene mutations in a cohort of 49 M0 patients. Mutation screening was performed either with SSCP (n=21) and/or denaturating High Performance Liquid Chromatography (dHPLC) (n=33), 5 cases were analyzed by both methods. SSCP screening of exons 3–5 of the AML1 gene was carried out at the genomic level. These exons cover the socalled Runt domain, which is most frequently mutated. Fragments with aberrant mobility were sequenced. With this method 5 cases were found to be mutated. Subsequently, to improve the screening efficiency an assay using dHPLC was established. Hereby, we screened the cDNA of patient samples for mutations in amino acid codons 1–277 of the AML1b transcript, where the Runt domain is located between codons 49 and 178. All 5 cases detected by SSCP were confirmed by dHPLC. Nine mutations were detected in the cohort of 28 cases (32%) which had not been analyzed by SSCP. In total, 14 of the 49 samples (29%) tested were identified to be mutated, which is a slightly higher frequency than previously reported. In the cohort of 35 AML1 non-mutated cases 20 (57%) had a normal karyotype and 15 (43%) an aberrant karyotypes, whereas only 6 of the 14 AML1 mutated cases (43%) had a normal karyotype (p=0.001). Three of the AML1 mutated cases (21%) also had FLT3 mutations. One had an FLT3-LM, one an FLT3-TKD mutation, and one case both LM and TKD mutations. Clinical follow up data were available for 33 patients (22 AML1 non- mutated, 11 AML1 mutated). The median OS and EFS of the AML1 non-mutated versus the mutated group was 276 days versus 63 days (p = 0.0679) and 276 vs. 63 days (p=0.0630) respectively. Thus the AML1 mutated cases tend to have a worse clinical outcome. When other AML subtypes were screened for AML1 mutations, i.e. M1 (n=26), M2 (n=21) and M4 (n=3), only 1 additional AML1 mutation was detected, confirming the highest prevalence of AML1 mutations in M0. In conclusion, 1) we established a new assay to screen for AML1 mutations. 2) We confirmed the high incidence of AML1 gene mutations in AML M0, both in cases with normal and aberrant karyotype. 3) For the first time we demonstrated that AML1 mutations define an unfavorable subentity in AML M0.

scholarly journals Tropical bat as mammalian model for skin carotenoid metabolism

2016 ◽  
Vol 113 (39) ◽  
pp. 10932-10937 ◽  
Author(s):  
Ismael Galván ◽  
Juan Garrido-Fernández ◽  
José Ríos ◽  
Antonio Pérez-Gálvez ◽  
Bernal Rodríguez-Herrera ◽  
...  
Keyword(s):  
High Performance ◽  
De Novo ◽  
Carotenoid Pigments ◽  
Physiological Mechanisms ◽  
Flight Mass Spectrometry ◽  
Animal Physiology ◽  
Bright Yellow ◽  
Carotenoid Metabolism ◽  
Potential Capacity ◽  
Bright Color

Animals cannot synthesize carotenoid pigments de novo, and must consume them in their diet. Most mammals, including humans, are indiscriminate accumulators of carotenoids but inefficiently distribute them to some tissues and organs, such as skin. This limits the potential capacity of these organisms to benefit from the antioxidant and immunostimulatory functions that carotenoids fulfill. Indeed, to date, no mammal has been known to have evolved physiological mechanisms to incorporate and deposit carotenoids in the skin or hair, and mammals have therefore been assumed to rely entirely on other pigments such as melanins to color their integument. Here we use high-performance liquid chromatography (HPLC) in combination with time-of-flight mass spectrometry (HPLC-TOF/MS) to show that the frugivorous Honduran white bat Ectophylla alba colors its skin bright yellow with the deposition of the xanthophyll lutein. The Honduran white bat is thus a mammalian model that may help developing strategies to improve the assimilation of lutein in humans to avoid macular degeneration. This represents a change of paradigm in animal physiology showing that some mammals actually have the capacity to accumulate dietary carotenoids in the integument. In addition, we have also discovered that the majority of the lutein in the skin of Honduran white bats is present in esterified form with fatty acids, thereby permitting longer-lasting coloration and suggesting bright color traits may have an overlooked role in the visual communication of bats.

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