| 1. |
- Birney, Ewan, et al.
(författare)
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Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
- 2007
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
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Tidskriftsartikel (refereegranskat)abstract
- We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
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| 2. |
- Liu, Fei, et al.
(författare)
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Draft genomes of four enterotoxigenic Escherichia coli (ETEC) clinical isolates from China and Bangladesh
- 2015
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Ingår i: Gut Pathogens. - : Springer Science and Business Media LLC. - 1757-4749. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- © 2015 Liu et al. Abstract Background: Enterotoxigenic Escherichia coli (ETEC) is an important pathogen that causes childhood and travelers' diarrhea. Here, we present the draft genomes of four ETEC isolates recovered from stool specimens of patients with diarrhea in Beijing, China and Dhaka, Bangladesh, respectively. Results: We obtained the draft genomes of ETEC strains CE516 and CE549 isolated in China, and E1777 and E2265 isolated in Bangladesh with a length of 5.1 Mbp, 4.9 Mbp, 5.1 Mbp, and 5.0 Mbp, respectively. Phylogenetic analysis indicated that the four strains grouped with the classical Escherichia coli phylogenetic groups A and B1 and three of them including a multi drug-resistant Chinese isolate (CE549) belonged to two major ETEC lineages distributed globally. The heat stable toxin (ST) structural gene (estA) was present in all strains except in strain CE516, and the heat labile toxin (LT) operon (eltAB) was present in all four genomes. Moreover, different resistance gene profiles were found between the ETEC strains. Conclusions: The draft genomes of the two isolates CE516 and CE549 represent the first genomes of ETEC reported from China. Though we revealed that ETEC is uncommon in Beijing, China, however, when it does occur, multi-drug resistance and ESBL positive isolates might pose a specific public health risk. Furthermore, this study advances our understanding of prevalence and antibiotic resistance of ETEC in China and adds to the number of sequenced strains from Bangladesh.
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| 3. |
- Joffré, Enrique, et al.
(författare)
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Analysis of Growth Phases of Enterotoxigenic Escherichia coli Reveals a Distinct Transition Phase before Entry into Early Stationary Phase with Shifts in Tryptophan, Fucose, and Putrescine Metabolism and Degradation of Neurotransmitter Precursors
- 2022
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Ingår i: Microbiology Spectrum. - : American Society for Microbiology. - 2165-0497. ; 10:4
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Tidskriftsartikel (refereegranskat)abstract
- Enterotoxigenic Escherichia coli (ETEC) is a major cause of diarrhea in children and adults in endemic areas. Gene regulation of ETEC during growth in vitro and in vivo needs to be further evaluated, and here we describe the full transcriptome and metabolome of ETEC during growth from mid-logarithmic growth to early stationary phase in rich medium (LB medium). We identified specific genes and pathways subjected to rapid transient alterations in gene expression and metabolite production during the transition from logarithmic to stationary growth. The transient phase was found to be different from the subsequent induction of early stationary phase-induced genes. The transient phase was characterized by the repression of genes and metabolites involved in organic substance transport. Genes involved in fucose and putrescine metabolism were upregulated, and genes involved in iron transport were repressed. Expression of toxins and colonization factors were not changed, suggesting retained virulence from mid-logarithmic to the start of the stationary phase. Metabolomic analyses showed that the transient phase was characterized by a drop of intracellular amino acids, e.g., l-tyrosine, l-tryptophan, l-phenylalanine, l-leucine, and l-glutamic acid, followed by increased levels at induction of stationary phase. A pathway enrichment analysis of the entire combined transcriptome and metabolome revealed that significant pathways during progression from logarithmic to early stationary phase are involved in the degradation of neurotransmitters aminobutyrate (GABA) and precursors of 5-hydroxytryptamine (serotonin). This work provides a comprehensive framework for further studies on transcriptional and metabolic regulation in pathogenic E. coli.IMPORTANCE We show that E. coli, exemplified by the pathogenic subspecies enterotoxigenic E. coli (ETEC), undergoes a stepwise transcriptional and metabolic transition into the stationary phase. At a specific entry point, E. coli induces activation and repression of specific pathways. This leads to a rapid decrease of intracellular levels of certain amino acids. The resulting metabolic activity leads to an intense but short peak of indole production, suggesting that this is the previously described “indole peak,” rapid decrease of intermediate molecules of bacterial neurotransmitters, increased putrescine and fucose uptake, increased glutathione levels, and decreased iron uptake. This specific transient shift in gene expression and metabolome is short-lived and disappears when bacteria enter the early stationary phase. We suggest that these changes mainly prepare bacteria for ceased growth, but based on the pathways involved, we could suggest that this transient phase substantially influences survival and virulence.
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| 4. |
- Sun, Qiang, et al.
(författare)
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Study protocol for One Health data collections, analyses and intervention of the Sino-Swedish integrated multisectoral partnership for antibiotic resistance containment (IMPACT)
- 2018
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Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: To effectively minimise the emergence and dissemination of antibiotic resistant bacteria, a holistic One Health approach is called for. The Sino-Swedish Integrated Multisectoral Partnership for Antibiotic Resistance Containment is a cross-sectoral and integrated project on antibiotic resistance, conducted in Shandong Province in China. This paper outlines the overall study protocol for the project. To our knowledge, this is the first research programme aiming to take a true holistic approach across multiple sectors simultaneously in China, and the first to incorporate both antibiotic use and infection prevention and control in addition to antibiotic resistance patterns. The project aims to address gaps in current knowledge and seeks to improve the situation through a system-wide intervention. By using a One Health approach we can address important research questions that individual discipline investigations are unable to. The results obtained should thus more closely reflect the world in which human health, animal health and the environment are inextricably and intimately interlinked.METHODS AND ANALYSIS: Both quantitative and qualitative studies are included for households from 12 villages, their surrounding environment and a tertiary care hospital in a nearby town. The studies include analyses of antibiotic consumption for humans and pigs; qualitative and quantitative data on perceptions, knowledge and attitudes; faecal carriage of extended spectrum β-lactamase and carbapenemase-producing Enterobacteriaceae from pigs and humans, and occurrence in household drinking water, surface water, waste water and clinical bacterial isolates from the hospital. Carriage of methicillin-resistant Staphylococcus aureus in humans, household pigs and clinical bacterial isolates is also investigated. Furthermore, potential inter-relationships between these sources are analysed. A multifaceted One Health intervention is designed and implemented in 6 of the 12 villages. Repeated and continuous data collections take place over 2 years, where the repeated data collection is performed after 1 year of intervention. Comparisons are made between intervention and control villages, before and after the intervention.ETHICS: Ethics approval was obtained from the first Affiliated Hospital, College of Medicine, Zhejiang University, China, reference number 2015#185 and 2015#283.
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