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Sökning: WFRF:(Boekel Jorrit)

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1.
  • Boekel, Jorrit, et al. (författare)
  • Comparative tissue transcriptomics reveal prompt inter-organ communication in response to local bacterial kidney infection
  • 2011
  • Ingår i: BMC Genomics. - 1471-2164 .- 1471-2164. ; 12, s. 123
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Background: Mucosal infections elicit inflammatory responses via regulated signaling pathways. Infection outcome depends strongly on early events occurring immediately when bacteria start interacting with cells in the mucosal membrane. Hitherto reported transcription profiles on host-pathogen interactions are strongly biased towards in vitro studies. To detail the local in vivo genetic response to infection, we here profiled host gene expression in a recent experimental model that assures high spatial and temporal control of uropathogenic Escherichia coli (UPEC) infection within the kidney of a live rat. Results: Transcriptional profiling of tissue biopsies from UPEC-infected kidney tissue revealed 59 differentially expressed genes 8 h post-infection. Their relevance for the infection process was supported by a Gene Ontology (GO) analysis. Early differential expression at 3 h and 5 h post-infection was of low statistical significance, which correlated to the low degree of infection. Comparative transcriptomics analysis of the 8 h data set and online available studies of early local infection and inflammation defined a core of 80 genes constituting a "General tissue response to early local bacterial infections". Among these, 25% were annotated as interferon-gamma (IFN-gamma) regulated. Subsequent experimental analyses confirmed a systemic increase of IFN-gamma in rats with an ongoing local kidney infection, correlating to splenic, rather than renal Ifng induction and suggested this inter-organ communication to be mediated by interleukin (IL)-23. The use of comparative transcriptomics allowed expansion of the statistical data handling, whereby relevant data could also be extracted from the 5 h data set. Out of the 31 differentially expressed core genes, some represented specific 5 h responses, illustrating the value of comparative transcriptomics when studying the dynamic nature of gene regulation in response to infections. Conclusion: Our hypothesis-free approach identified components of infection-associated multi-cellular tissue responses and demonstrated how a comparative analysis allows retrieval of relevant information from lower-quality data sets. The data further define marked representation of IFN-gamma responsive genes and a prompt inter-organ communication as a hallmark of an early local tissue response to infection.</p>
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2.
  • Boekel, Jorrit, et al. (författare)
  • Multi-omic data analysis using Galaxy
  • 2015
  • Ingår i: Nature Biotechnology. - 1087-0156 .- 1546-1696. ; 33:2, s. 137-9
  • Tidskriftsartikel (refereegranskat)
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3.
  • Boekel, Jorrit (författare)
  • Tissue responses and host transcriptomics in bacterial infections
  • 2011
  • Doktorsavhandling (övrigt vetenskapligt)abstract
    • Bacterial infections can damage host tissue and are as such a potential threat to their hosts. To protect themselves from pathogens, hosts therefore can employ diverse immune reactions. When bacteria are recognized by their hosts, complex signaling cascades are triggered that lead to an in ux of specialized immune cells into the infected tissue and a change in tissue integrity. The in- ammation that is mounted may eliminate the pathogens, but will also cause substantial tissue damage. The foundation for the in ammatory process is laid early, in the rst 12 hours of infection. This thesis aims to reveal host responses within this early time frame. While in vitro studies can yield highly detailed data on subjects as proteinprotein and cell-bacterial interactions, they cannot reproduce all aspects that occur in a live animal, such as immune in ltration, nerve, and hormone e ects. We have developed a kidney infection model of bacterial infection to study early whole-host responses to bacteria. Using micropuncture techniques, we delivered bacteria to a known nephron, from where the infection progressed. Within hours, we observed numerous physiological changes of the tissue volume bordering the infection. Infection kinetics could be visualized and showed markedly faster host responses to haemolysin (Hly)-carrying bacteria compared to Hly-knockouts. Tissue oxygen levels decreased in response to infection, possibly caused both by blood ow restriction combined with epithelial oxygen consumption. Blood ow shutdown at the infected nephron was due to activation of the coagulation cascade. Coagulation also protected against sepsis, as animals died due to bacteremia when this cascade was inhibited. Some of these phenomena could be found in the host transcriptome. We also found that a core of common gene expression exists in live host innate immune responses by applying bioinformatic methods on the gene expression measurements. This core had a strong IFN-γ signature, a cytokine which we consequently found increased in the blood stream, and expressed by cells in the spleen. We go on to show that IFN-γ downregulates transcription of several neutrophil-attracting chemokines, and that this does not occur through canonical e ectors of either IFN-γ or in ammatory signaling pathways. The data I present here show that using a live host infection model can reveal host processes that cannot be found using in vitro models. By combining this model with analysis methods that yield detailed data, early responses could be studied. The data show the importance of live models for discovering unknown contributors and functions in in ammation, which may lead to possible future medicine development.
4.
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5.
  • Grüning, Björn, et al. (författare)
  • Bioconda: A sustainable and comprehensive software distribution for the life sciences
  • 2017
  • Annan publikation (övrigt vetenskapligt)abstract
    • We present Bioconda (https://bioconda.github.io), a distribution of bioinformatics software for the lightweight, multi-platform and language-agnostic package manager Conda. Currently, Bioconda offers a collection of over 3000 software packages, which is continuously maintained, updated, and extended by a growing global community of more than 200 contributors. Bioconda improves analysis reproducibility by allowing users to define isolated environments with defined software versions, all of which are easily installed and managed without administrative privileges.
6.
  • Hessa, Tara, et al. (författare)
  • Recognition of transmembrane helices by the endoplasmic reticulum translocon
  • 2005
  • Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 433:7024, s. 377-381
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Membrane proteins depend on complex translocation machineries for insertion into target membranes. Although it has long been known that an abundance of nonpolar residues in transmembrane helices is the principal criterion for membrane insertion, the specific sequence-coding for transmembrane helices has not been identified. By challenging the endoplasmic reticulum Sec61 translocon with an extensive set of designed polypeptide segments, we have determined the basic features of this code, including a 'biological' hydrophobicity scale. We find that membrane insertion depends strongly on the position of polar residues within transmembrane segments, adding a new dimension to the problem of predicting transmembrane helices from amino acid sequences. Our results indicate that direct protein - lipid interactions are critical during translocon-mediated membrane insertion.</p>
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7.
  • Johansson, Henrik J., et al. (författare)
  • Breast cancer quantitative proteome and proteogenomic landscape
  • 2019
  • Ingår i: Nature Communications. - NATURE PUBLISHING GROUP. - 2041-1723 .- 2041-1723. ; 10
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>In the preceding decades, molecular characterization has revolutionized breast cancer (BC) research and therapeutic approaches. Presented herein, an unbiased analysis of breast tumor proteomes, inclusive of 9995 proteins quantified across all tumors, for the first time recapitulates BC subtypes. Additionally, poor-prognosis basal-like and luminal B tumors are further subdivided by immune component infiltration, suggesting the current classification is incomplete. Proteome-based networks distinguish functional protein modules for breast tumor groups, with co-expression of EGFR and MET marking ductal carcinoma in situ regions of normal-like tumors and lending to a more accurate classification of this poorly defined subtype. Genes included within prognostic mRNA panels have significantly higher than average mRNA-protein correlations, and gene copy number alterations are dampened at the protein-level; underscoring the value of proteome quantification for prognostication and phenotypic classification. Furthermore, protein products mapping to non-coding genomic regions are identified; highlighting a potential new class of tumor-specific immunotherapeutic targets.</p>
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8.
  • Johansson, Henrik J., et al. (författare)
  • Breast cancer quantitative proteome and proteogenomic landscape
  • 2019
  • Ingår i: Nature Communications. - 2041-1723 .- 2041-1723. ; 10
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>In the preceding decades, molecular characterization has revolutionized breast cancer (BC) research and therapeutic approaches. Presented herein, an unbiased analysis of breast tumor proteomes, inclusive of 9995 proteins quantified across all tumors, for the first time recapitulates BC subtypes. Additionally, poor-prognosis basal-like and luminal B tumors are further subdivided by immune component infiltration, suggesting the current classification is incomplete. Proteome-based networks distinguish functional protein modules for breast tumor groups, with co-expression of EGFR and MET marking ductal carcinoma in situ regions of normal-like tumors and lending to a more accurate classification of this poorly defined subtype. Genes included within prognostic mRNA panels have significantly higher than average mRNA-protein correlations, and gene copy number alterations are dampened at the protein-level; underscoring the value of proteome quantification for prognostication and phenotypic classification. Furthermore, protein products mapping to non-coding genomic regions are identified; highlighting a potential new class of tumor-specific immunotherapeutic targets.</p>
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9.
  • Johansson, Henrik J., et al. (författare)
  • Breast cancer quantitative proteome and proteogenomic landscape
  • 2019
  • Ingår i: Nature Communications. - NATURE PUBLISHING GROUP. - 2041-1723 .- 2041-1723. ; 10
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>In the preceding decades, molecular characterization has revolutionized breast cancer (BC) research and therapeutic approaches. Presented herein, an unbiased analysis of breast tumor proteomes, inclusive of 9995 proteins quantified across all tumors, for the first time recapitulates BC subtypes. Additionally, poor-prognosis basal-like and luminal B tumors are further subdivided by immune component infiltration, suggesting the current classification is incomplete. Proteome-based networks distinguish functional protein modules for breast tumor groups, with co-expression of EGFR and MET marking ductal carcinoma in situ regions of normal-like tumors and lending to a more accurate classification of this poorly defined subtype. Genes included within prognostic mRNA panels have significantly higher than average mRNA-protein correlations, and gene copy number alterations are dampened at the protein-level; underscoring the value of proteome quantification for prognostication and phenotypic classification. Furthermore, protein products mapping to non-coding genomic regions are identified; highlighting a potential new class of tumor-specific immunotherapeutic targets.</p>
10.
  • Melican, Keria, et al. (författare)
  • Bacterial infection-mediated mucosal signalling induces local renal ischaemia as a defence against sepsis
  • 2008
  • Ingår i: Cellular Microbiology. - 1462-5814 .- 1462-5822. ; 10:10, s. 1987-1998
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Ascending urinary tract infections can cause extensive damage to kidney structure and function. We have used a number of advanced techniques including multiphoton microscopy to investigate the crucial early phases of uropathogenic Escherichia coli induced pyelonephritis within a living animal. Our results reveal a previously undescribed innate vascular response to mucosal infection, allowing isolation and eradication of the pathogen. The extremely rapid host response to mucosal infection was highlighted by the triggering of a cascade of events within 3-4 h. Epithelial signalling produced an increase in cellular O-2 consumption and affected microvascular flow by clotting, causing localized ischaemia. Subsequent ischaemic damage affected pathophysiology with actin re-arrangement and epithelial sloughing leading to paracellular bacterial movement. A denuded tubular basement membrane is shown to hinder immediate dissemination of bacteria, giving the host time to isolate the infection by clotting. Suppression of clotting by heparin treatment caused fatal urosepsis. Clinically these findings may be relevant in antibiotics delivery in pyelonephritis patients and to the use of anticoagulants in sepsis.</p>
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