36 research outputs found
Multi-agent architecture for waste minimisation in beef supply chain
Food waste is an alarming issue pertaining to the rising global hunger, huge environmental footprint, and high monetary value. In developing and developed nations, it occurs primarily due to inefficiencies upstream and downstream of the supply chain respectively. A common factor in both developed and developing nations is product flow within the supply chain from farms to retailers. This study aims to identify the root causes of waste generated across the product flow of the beef supply chain from farm to retailer. A workshop involving twenty practitioners of the beef industry was conducted and the collected information was transcribed and coded to generate a current reality tree, which assisted in identifying root causes of waste in the entire beef supply chain. A multi-agent architecture framework spanning the entire beef supply chain from farm to retailer is proposed, which is composed of autonomous agents capable of bringing all segments of the beef industry on a single platform and collaboratively assist them in mitigating root causes of waste. The proposed framework will aid the practitioners in the beef industry to reduce waste, improve their operational efficiency thereby raising food security, economic development whilst curbing their carbon footprint
Metabolic re-wiring of isogenic breast epithelial cell lines following epithelial to mesenchymal transition.
To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked FilesEpithelial to mesenchymal transition (EMT) has implications in tumor progression and metastasis. Metabolic alterations have been described in cancer development but studies focused on the metabolic re-wiring that takes place during EMT are still limited. We performed metabolomics profiling of a breast epithelial cell line and its EMT derived mesenchymal phenotype to create genome-scale metabolic models descriptive of both cell lines. Glycolysis and OXPHOS were higher in the epithelial phenotype while amino acid anaplerosis and fatty acid oxidation fueled the mesenchymal phenotype. Through comparative bioinformatics analysis, PPAR-γ1, PPAR- γ2 and AP-1 were found to be the most influential transcription factors associated with metabolic re-wiring. In silico gene essentiality analysis predicts that the LAT1 neutral amino acid transporter is essential for mesenchymal cell survival. Our results define metabolic traits that distinguish an EMT derived mesenchymal cell line from its epithelial progenitor and may have implications in cancer progression and metastasis. Furthermore, the tools presented here can aid in identifying critical metabolic nodes that may serve as therapeutic targets aiming to prevent EMT and inhibit metastatic dissemination.Icelandic Research Counci
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Critical application modeling in time in local networks with plug-in passing.
Várias aplicações podem simultaneamente, ser suportadas por um Sistema de Comunicação, compartilhando os recursos disponíveis. Dentre estas aplicações, algumas denominadas de Aplicações Criticas, podem apresentar requisitos bastante exigentes com relação ao desempenho do sistema. Nesta tese, apresenta-se uma caracterização de Aplicações Criticas em Sistemas de Comunicação genéricos, e se estabelece os critériospara o julgamento da criticidade destas aplicações, relativo ao desempenho destes sistemas. Denomina-se esta caracterização e critérios para o julgamento da criticidade, como Modelagem de Aplicações Criticas. As Redes Locais de Computadores (RLCs) podem ser empregadas como sistema de suporte de comunicação para um variado espectro de aplicações, e.g. automação de escritório, controle de processos, processamento distribuido. Estas aplicações são criticas no tempo. Os modelos analíticos existentes, usados para o estudo do desempenho das RLCs são deficientes em se tratando de aplicações criticas. Apresenta-se nesta tese, modelos analíticos para a Modelagem de Aplicações Criticas no tempo em RLCs com Passagem de Ficha. 0 estudo da integração dos tráfegos de voz e dados é importante nas aplicações de automação de escritório. Com base na Modelagem de Aplicações Criticas em RLCs com Passagem de Ficha, sugere-se um modelo aproximado para o estudo da integração dos tráfegos de vos e dados nestas redes. Através da solução deste modelo, extrai-se informações acerca da Probabilidade de Perda dos pacotes de vos, cuja determinação era possível apenas,
através de estudos de simulação.For the purpose of resource sharing, various applications may be integrated in a communication system. Some of these application may have extreme or critical requirements on the system performance. Such applications are said to be Critical
Applications. This thesis deals with the characterization and analytical modelling of Critical Applications on generic communication systems. Criteria for judging the criticalness of
an application with respect to the performance of a communication system, are also discussed. The proposed modelling approach is applied to Token Passing
Local Area Networks (LANs) integrating voice and data traffic, when the former is assumed critical with respect to packet transit delay in the communication subnetwork. The results obtained extend the use of analytical models to performance evaluation studies of LANs under voice traffic by considering more realistic probability distribuition for (voice) packet arrivals to the subnetwork. The analytical results also show performance trends whose prior observation had been possible through simulation studies only
EGFR Signal-Network Reconstruction Demonstrates Metabolic Crosstalk in EMT.
To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files.
This article is open access.Epithelial to mesenchymal transition (EMT) is an important event during development and cancer metastasis. There is limited understanding of the metabolic alterations that give rise to and take place during EMT. Dysregulation of signalling pathways that impact metabolism, including epidermal growth factor receptor (EGFR), are however a hallmark of EMT and metastasis. In this study, we report the investigation into EGFR signalling and metabolic crosstalk of EMT through constraint-based modelling and analysis of the breast epithelial EMT cell model D492 and its mesenchymal counterpart D492M. We built an EGFR signalling network for EMT based on stoichiometric coefficients and constrained the network with gene expression data to build epithelial (EGFR_E) and mesenchymal (EGFR_M) networks. Metabolic alterations arising from differential expression of EGFR genes was derived from a literature review of AKT regulated metabolic genes. Signaling flux differences between EGFR_E and EGFR_M models subsequently allowed metabolism in D492 and D492M cells to be assessed. Higher flux within AKT pathway in the D492 cells compared to D492M suggested higher glycolytic activity in D492 that we confirmed experimentally through measurements of glucose uptake and lactate secretion rates. The signaling genes from the AKT, RAS/MAPK and CaM pathways were predicted to revert D492M to D492 phenotype. Follow-up analysis of EGFR signaling metabolic crosstalk in three additional breast epithelial cell lines highlighted variability in in vitro cell models of EMT. This study shows that the metabolic phenotype may be predicted by in silico analyses of gene expression data of EGFR signaling genes, but this phenomenon is cell-specific and does not follow a simple trend.Icelandic Research Fund (RANNIS)
130591-051
152358-051
152369-05
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Pangenome Analytics Reveal Two-Component Systems as Conserved Targets in ESKAPEE Pathogens.
The two-component system (TCS) helps bacteria sense and respond to environmental stimuli through histidine kinases and response regulators. TCSs are the largest family of multistep signal transduction processes, and they are involved in many important cellular processes such as antibiotic resistance, pathogenicity, quorum sensing, osmotic stress, and biofilms. Here, we perform the first comprehensive study to highlight the role of TCSs as potential drug targets against ESKAPEE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Enterobacter spp., and Escherichia coli) pathogens through annotation, mapping, pangenomic status, gene orientation, and sequence variation analysis. The distribution of the TCSs is group specific with regard to Gram-positive and Gram-negative bacteria, except for KdpDE. The TCSs among ESKAPEE pathogens form closed pangenomes, except for Pseudomonas aeruginosa Furthermore, their conserved nature due to closed pangenomes might make them good drug targets. Fitness score analysis suggests that any mutation in some TCSs such as BaeSR, ArcBA, EvgSA, and AtoSC, etc., might be lethal to the cell. Taken together, the results of this pangenomic assessment of TCSs reveal a range of strategies deployed by the ESKAPEE pathogens to manifest pathogenicity and antibiotic resistance. This study further suggests that the conserved features of TCSs might make them an attractive group of potential targets with which to address antibiotic resistance.IMPORTANCE The ESKAPEE pathogens are the leading cause of health care-associated infections worldwide. Two-component systems (TCSs) can be used as effective targets against pathogenic bacteria since they are ubiquitous and manage various vital functions such as antibiotic resistance, virulence, biofilms, quorum sensing, and pH balance, among others. This study provides a comprehensive overview of the pangenomic status of the TCSs among ESKAPEE pathogens. The annotation and pangenomic analysis of TCSs show that they are significantly distributed and conserved among the pathogens, as most of them form closed pangenomes. Furthermore, our analysis also reveals that the removal of the TCSs significantly affects the fitness of the cell. Hence, they may be used as promising drug targets against bacteria
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Elucidation of Regulatory Modes for Five Two-Component Systems in Escherichia coli Reveals Novel Relationships
Escherichia coli uses two-component systems (TCSs) to respond to environmental signals. TCSs affect gene expression and are parts of E. coli's global transcriptional regulatory network (TRN). Here, we identified the regulons of five TCSs in E. coli MG1655: BaeSR and CpxAR, which were stimulated by ethanol stress; KdpDE and PhoRB, induced by limiting potassium and phosphate, respectively; and ZraSR, stimulated by zinc. We analyzed RNA-seq data using independent component analysis (ICA). ChIP-exo data were used to validate condition-specific target gene binding sites. Based on these data, we do the following: (i) identify the target genes for each TCS; (ii) show how the target genes are transcribed in response to stimulus; and (iii) reveal novel relationships between TCSs, which indicate noncognate inducers for various response regulators, such as BaeR to iron starvation, CpxR to phosphate limitation, and PhoB and ZraR to cell envelope stress. Our understanding of the TRN in E. coli is thus notably expanded.IMPORTANCE E. coli is a common commensal microbe found in the human gut microenvironment; however, some strains cause diseases like diarrhea, urinary tract infections, and meningitis. E. coli's two-component systems (TCSs) modulate target gene expression, especially related to virulence, pathogenesis, and antimicrobial peptides, in response to environmental stimuli. Thus, it is of utmost importance to understand the transcriptional regulation of TCSs to infer bacterial environmental adaptation and disease pathogenicity. Utilizing a combinatorial approach integrating RNA sequencing (RNA-seq), independent component analysis, chromatin immunoprecipitation coupled with exonuclease treatment (ChIP-exo), and data mining, we suggest five different modes of TCS transcriptional regulation. Our data further highlight noncognate inducers of TCSs, which emphasizes the cross-regulatory nature of TCSs in E. coli and suggests that TCSs may have a role beyond their cognate functionalities. In summary, these results can lead to an understanding of the metabolic capabilities of bacteria and correctly predict complex phenotype under diverse conditions, especially when further incorporated with genome-scale metabolic models
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Elucidation of Regulatory Modes for Five Two-Component Systems in Escherichia coli Reveals Novel Relationships.
Escherichia coli uses two-component systems (TCSs) to respond to environmental signals. TCSs affect gene expression and are parts of E. coli's global transcriptional regulatory network (TRN). Here, we identified the regulons of five TCSs in E. coli MG1655: BaeSR and CpxAR, which were stimulated by ethanol stress; KdpDE and PhoRB, induced by limiting potassium and phosphate, respectively; and ZraSR, stimulated by zinc. We analyzed RNA-seq data using independent component analysis (ICA). ChIP-exo data were used to validate condition-specific target gene binding sites. Based on these data, we do the following: (i) identify the target genes for each TCS; (ii) show how the target genes are transcribed in response to stimulus; and (iii) reveal novel relationships between TCSs, which indicate noncognate inducers for various response regulators, such as BaeR to iron starvation, CpxR to phosphate limitation, and PhoB and ZraR to cell envelope stress. Our understanding of the TRN in E. coli is thus notably expanded.IMPORTANCEE. coli is a common commensal microbe found in the human gut microenvironment; however, some strains cause diseases like diarrhea, urinary tract infections, and meningitis. E. coli's two-component systems (TCSs) modulate target gene expression, especially related to virulence, pathogenesis, and antimicrobial peptides, in response to environmental stimuli. Thus, it is of utmost importance to understand the transcriptional regulation of TCSs to infer bacterial environmental adaptation and disease pathogenicity. Utilizing a combinatorial approach integrating RNA sequencing (RNA-seq), independent component analysis, chromatin immunoprecipitation coupled with exonuclease treatment (ChIP-exo), and data mining, we suggest five different modes of TCS transcriptional regulation. Our data further highlight noncognate inducers of TCSs, which emphasizes the cross-regulatory nature of TCSs in E. coli and suggests that TCSs may have a role beyond their cognate functionalities. In summary, these results can lead to an understanding of the metabolic capabilities of bacteria and correctly predict complex phenotype under diverse conditions, especially when further incorporated with genome-scale metabolic models