Publications by authors named "Lisa Öberg"

18 Publications

  • Page 1 of 1

Impaired Differentiation of COPD Bronchial Epithelial Cells Grown on Bronchial Scaffolds.

Am J Respir Cell Mol Biol 2021 Apr 21. Epub 2021 Apr 21.

AstraZeneca, Gothenburg, Sweden;

Chronic obstructive pulmonary disease (COPD) is characterized by airway inflammation, small airway remodeling and emphysema. Airway remodeling in COPD patients involves both the airway epithelium and the subepithelial extracellular matrix (ECM). However, it is currently unknown how epithelial remodeling in COPD airways depends on the relative influence from inherent defects in the epithelial cells and alterations in the ECM. To address this, we analyzed global gene expression in COPD and normal human bronchial epithelial cells (HBEC) after repopulation on decellularized bronchial scaffolds derived from COPD patients or non-COPD donors. COPD HBEC grown on bronchial scaffolds showed an impaired ability to initiate ciliated cell differentiation, which was evident on all scaffolds regardless of their origin. In addition, while normal HBEC were less affected by the disease state of the bronchial scaffolds, COPD HBEC showed a gene expression pattern indicating increased proliferation and a retained basal cell phenotype when grown on COPD compared to normal bronchial scaffolds. Mass spectrometry identified thirteen matrisome proteins as differentially abundant between COPD and normal bronchial scaffolds. These observations are consistent with COPD pathology and suggest that both epithelial cells and the ECM contribute to epithelial cell remodeling in COPD airways. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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http://dx.doi.org/10.1165/rcmb.2019-0395OCDOI Listing
April 2021

Dual Role For A MEK Inhibitor As A Modulator Of Inflammation And Host Defense Mechanisms With Potential Therapeutic Application In COPD.

Int J Chron Obstruct Pulmon Dis 2019 26;14:2611-2624. Epub 2019 Nov 26.

Translational Science and Experimental Medicine, Research and Early Development, RIA, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.

Background: Unlike p38 mitogen-activated protein Kinases (MAPK) that has been extensively studied in the context of lung-associated pathologies in COPD, the role of the dual-specificity mitogen-activated protein kinase kinase (MEK1/2) or its downstream signaling molecule extracellular signal-regulated kinases 1/2 (ERK1/2) in COPD is poorly understood.

Objectives: The aim of this study was to address whether MEK1/2 pathway activation is linked to COPD and that targeting this pathway can improve lung inflammation through decreased immune-mediated inflammatory responses without compromising bacterial clearance.

Methods: Association of MEK1/2 pathway activation to COPD was investigated by immunohistochemistry using lung tissue biopsies from COPD and healthy individuals and through analysis of sputum gene expression data from COPD patients. The anti-inflammatory effect of MEK1/2 inhibition was assessed on cytokine release from lipopolysaccharide-stimulated alveolar macrophages. The effect of MEK1/2 inhibition on bacterial clearance was assessed using killing assays with RAW 264.7 macrophage cell line and human neutrophils.

Results: We report here MEK1/2 pathway activation demonstrated by increased pERK1/2 staining in bronchial epithelium and by the presence of MEK gene activation signature in sputum samples from COPD patients. Inhibition of MEK1/2 resulted in a superior anti-inflammatory effect in human alveolar macrophages in comparison to a p38 inhibitor. Furthermore, MEK1/2 inhibition led to an increase in bacterial killing in human neutrophils and RAW 264.7 cells that was not observed with the p38 inhibitor.

Conclusion: Our data demonstrate the activation of MEK1/2 pathway in COPD and highlight a dual function of MEK1/2 inhibition in improving host defense responses whilst also controlling inflammation.
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http://dx.doi.org/10.2147/COPD.S211619DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6885002PMC
August 2020

The Mitogenome of Norway Spruce and a Reappraisal of Mitochondrial Recombination in Plants.

Genome Biol Evol 2020 01;12(1):3586-3598

Department of Ecology and Environmental Science, Umeå Plant Science Center, Umeå University, Sweden.

Plant mitogenomes can be difficult to assemble because they are structurally dynamic and prone to intergenomic DNA transfers, leading to the unusual situation where an organelle genome is far outnumbered by its nuclear counterparts. As a result, comparative mitogenome studies are in their infancy and some key aspects of genome evolution are still known mainly from pregenomic, qualitative methods. To help address these limitations, we combined machine learning and in silico enrichment of mitochondrial-like long reads to assemble the bacterial-sized mitogenome of Norway spruce (Pinaceae: Picea abies). We conducted comparative analyses of repeat abundance, intergenomic transfers, substitution and rearrangement rates, and estimated repeat-by-repeat homologous recombination rates. Prompted by our discovery of highly recombinogenic small repeats in P. abies, we assessed the genomic support for the prevailing hypothesis that intramolecular recombination is predominantly driven by repeat length, with larger repeats facilitating DNA exchange more readily. Overall, we found mixed support for this view: Recombination dynamics were heterogeneous across vascular plants and highly active small repeats (ca. 200 bp) were present in about one-third of studied mitogenomes. As in previous studies, we did not observe any robust relationships among commonly studied genome attributes, but we identify variation in recombination rates as a underinvestigated source of plant mitogenome diversity.
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http://dx.doi.org/10.1093/gbe/evz263DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6944214PMC
January 2020

Arpin is critical for phagocytosis in macrophages and is targeted by human rhinovirus.

EMBO Rep 2020 01 13;21(1):e47963. Epub 2019 Nov 13.

Université de Paris, Institut Cochin, INSERM, U1016, CNRS, UMR 8104, Paris, France.

Human rhinovirus is a causative agent of severe exacerbations of chronic obstructive pulmonary disease (COPD). COPD is characterised by an increased number of alveolar macrophages with diminished phagocytic functions, but how rhinovirus infection affects macrophage function is still unknown. Here, we describe that human rhinovirus 16 impairs bacterial uptake and receptor-mediated phagocytosis in macrophages. The stalled phagocytic cups contain accumulated F-actin. Interestingly, we find that human rhinovirus 16 downregulates the expression of Arpin, a negative regulator of the Arp2/3 complex. Importantly, re-expression of the protein rescues defective internalisation in human rhinovirus 16-treated cells, demonstrating that Arpin is a key factor targeted to impair phagocytosis. We further show that Arpin is required for efficient uptake of multiple targets, for F-actin cup formation and for successful phagosome completion in macrophages. Interestingly, Arpin is recruited to sites of membrane extension and phagosome closure. Thus, we identify Arpin as a central actin regulator during phagocytosis that it is targeted by human rhinovirus 16, allowing the virus to perturb bacterial internalisation and phagocytosis in macrophages.
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http://dx.doi.org/10.15252/embr.201947963DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6945061PMC
January 2020

Genetic variations in A20 DUB domain provide a genetic link to citrullination and neutrophil extracellular traps in systemic lupus erythematosus.

Ann Rheum Dis 2019 10 12;78(10):1363-1370. Epub 2019 Jul 12.

Research and Early Development, Respiratory, Inflammation and Autoimmune, BioPharmaceuticals R&D, AstraZeneca R&D Gothenburg, Mölndal, Sweden

Objectives: Genetic variations in (A20) de-ubiquitinase (DUB) domain increase the risk of systemic lupus erythematosus (SLE) and rheumatoid arthritis. A20 is a negative regulator of NF-κB but the role of its DUB domain and related genetic variants remain unclear. We aimed to study the functional effects of A20 DUB-domain alterations in immune cells and understand its link to SLE pathogenesis.

Methods: CRISPR/Cas9 was used to generate human U937 monocytes with A20 DUB-inactivating knock-in (KI) mutation. Whole genome RNA-sequencing was used to identify differentially expressed genes between WT and KI cells. Functional studies were performed in A20 U937 cells and in immune cells from A20 mice and genotyped healthy individuals with A20 DUB polymorphism rs2230926. Neutrophil extracellular trap (NET) formation was addressed ex vivo in neutrophils from A20 mice and SLE-patients with rs2230926.

Results: Genetic disruption of A20 DUB domain in human and murine myeloid cells did not give rise to enhanced NF-κB signalling. Instead, cells with mutation or rs2230926 polymorphism presented an upregulated expression of , an enzyme regulating protein citrullination and NET formation, two key mechanisms in autoimmune pathology. A20 cells exhibited enhanced protein citrullination and extracellular trap formation, which could be suppressed by selective PAD4 inhibition. Moreover, SLE-patients with rs2230926 showed increased NETs and increased frequency of autoantibodies to citrullinated epitopes.

Conclusions: We propose that genetic alterations disrupting the A20 DUB domain mediate increased susceptibility to SLE through the upregulation of with resultant protein citrullination and extracellular trap formation.
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http://dx.doi.org/10.1136/annrheumdis-2019-215434DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6788882PMC
October 2019

Upper Airway Cell Transcriptomics Identify a Major New Immunological Phenotype with Strong Clinical Correlates in Young Children with Acute Wheezing.

J Immunol 2019 03 11;202(6):1845-1858. Epub 2019 Feb 11.

Telethon Kids Institute, The University of Western Australia, Perth, Western Australia 6008, Australia;

Asthma exacerbations are triggered by rhinovirus infections. We employed a systems biology approach to delineate upper-airway gene network patterns underlying asthma exacerbation phenotypes in children. Cluster analysis unveiled distinct IRF7 versus IRF7 molecular phenotypes, the former exhibiting robust upregulation of Th1/type I IFN responses and the latter an alternative signature marked by upregulation of cytokine and growth factor signaling and downregulation of IFN-γ. The two phenotypes also produced distinct clinical phenotypes. For IRF7 children, symptom duration prior to hospital presentation was more than twice as long from initial symptoms ( = 0.011) and nearly three times as long for cough ( < 0.001), the odds ratio of admission to hospital was increased more than 4-fold ( = 0.018), and time to recurrence was shorter ( = 0.015). In summary, our findings demonstrate that asthma exacerbations in children can be divided into IRF7 versus IRF7 phenotypes with associated differences in clinical phenotypes.
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http://dx.doi.org/10.4049/jimmunol.1800178DOI Listing
March 2019

Epithelial IL-6 trans-signaling defines a new asthma phenotype with increased airway inflammation.

J Allergy Clin Immunol 2019 02 11;143(2):577-590. Epub 2018 Jun 11.

Experimental Asthma and Allergy Research, Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden.

Background: Although several studies link high levels of IL-6 and soluble IL-6 receptor (sIL-6R) to asthma severity and decreased lung function, the role of IL-6 trans-signaling (IL-6TS) in asthmatic patients is unclear.

Objective: We sought to explore the association between epithelial IL-6TS pathway activation and molecular and clinical phenotypes in asthmatic patients.

Methods: An IL-6TS gene signature obtained from air-liquid interface cultures of human bronchial epithelial cells stimulated with IL-6 and sIL-6R was used to stratify lung epithelial transcriptomic data (Unbiased Biomarkers in Prediction of Respiratory Disease Outcomes [U-BIOPRED] cohorts) by means of hierarchical clustering. IL-6TS-specific protein markers were used to stratify sputum biomarker data (Wessex cohort). Molecular phenotyping was based on transcriptional profiling of epithelial brushings, pathway analysis, and immunohistochemical analysis of bronchial biopsy specimens.

Results: Activation of IL-6TS in air-liquid interface cultures reduced epithelial integrity and induced a specific gene signature enriched in genes associated with airway remodeling. The IL-6TS signature identified a subset of patients with IL-6TS-high asthma with increased epithelial expression of IL-6TS-inducible genes in the absence of systemic inflammation. The IL-6TS-high subset had an overrepresentation of frequent exacerbators, blood eosinophilia, and submucosal infiltration of T cells and macrophages. In bronchial brushings Toll-like receptor pathway genes were upregulated, whereas expression of cell junction genes was reduced. Sputum sIL-6R and IL-6 levels correlated with sputum markers of remodeling and innate immune activation, in particular YKL-40, matrix metalloproteinase 3, macrophage inflammatory protein 1β, IL-8, and IL-1β.

Conclusions: Local lung epithelial IL-6TS activation in the absence of type 2 airway inflammation defines a novel subset of asthmatic patients and might drive airway inflammation and epithelial dysfunction in these patients.
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http://dx.doi.org/10.1016/j.jaci.2018.05.026DOI Listing
February 2019

Bronchial extracellular matrix from COPD patients induces altered gene expression in repopulated primary human bronchial epithelial cells.

Sci Rep 2018 02 22;8(1):3502. Epub 2018 Feb 22.

Bioscience Regeneration Department, Respiratory, Inflammation and Autoimmunity, IMED Biotech Unit, AstraZeneca, Gothenburg, Sweden.

Chronic obstructive pulmonary disease (COPD) is a serious global health problem characterized by chronic airway inflammation, progressive airflow limitation and destruction of lung parenchyma. Remodeling of the bronchial airways in COPD includes changes in both the bronchial epithelium and the subepithelial extracellular matrix (ECM). To explore the impact of an aberrant ECM on epithelial cell phenotype in COPD we developed a new ex vivo model, in which normal human bronchial epithelial (NHBE) cells repopulate and differentiate on decellularized human bronchial scaffolds derived from COPD patients and healthy individuals. By using transcriptomics, we show that bronchial ECM from COPD patients induces differential gene expression in primary NHBE cells when compared to normal bronchial ECM. The gene expression profile indicated altered activity of upstream mediators associated with COPD pathophysiology, including hepatocyte growth factor, transforming growth factor beta 1 and platelet-derived growth factor B, which suggests that COPD-related changes in the bronchial ECM contribute to the defective regenerative ability in the airways of COPD patients.
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http://dx.doi.org/10.1038/s41598-018-21727-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5823945PMC
February 2018

Theoretical studies of the second step of the nitric oxide synthase reaction: Electron tunneling prevents uncoupling.

J Inorg Biochem 2018 04 10;181:28-40. Epub 2018 Jan 10.

Department of Medicinal Chemistry, IMED RIA, AstraZeneca R&D Gothenburg, Pepparedsleden 1, 431 83 Mölndal, Sweden.

Nitric oxide (NO·) is a messenger molecule with diverse physiological roles including host defense, neurotransmission and vascular function. The synthesis of NO· from l-arginine is catalyzed by NO-synthases and occurs in two steps through the intermediary N-hydroxy-l-arginine (NHA). In both steps the P450-like reaction cycle is coupled with the redox cycle of the cofactor tetrahydrobiopterin (HB). The mechanism of the second step is studied by Density Functional Theory calculations to ascertain the canonical sequence of proton and electron transfer (PT and ET) events. The proposed mechanism is controlled by the interplay of two electron donors, HB and NHA. Consistent with experimental data, the catalytic cycle proceeds through the ferric-hydroperoxide complex (Cpd 0) and the following aqua-ferriheme resting state, and involves interim partial oxidation of HB. The mechanism starts with formation of Cpd 0 from the ferrous-dioxy reactant complex by PT from the C-ring heme propionate coupled with hole transfer to HB through the highest occupied π-orbital of NHA as a bridge. This enables PT from NHA· to the proximal oxygen leading to the shallow ferriheme-HO oxidant. Subsequent Fenton-like peroxide bond cleavage triggered by ET from the NHA-derived iminoxy-radical leads to the protonated Cpd II diradicaloid singlet stabilized by spin delocalization in HB, and the closed-shell coordination complex of HO with iminoxy-cation. The complex is converted to the transient C-adduct, which releases intended products upon PT to the ferriheme-HO complex coupled with ET to the HB·. Deferred ET from the substrate or undue ET from/to the cofactor leads to side products.
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http://dx.doi.org/10.1016/j.jinorgbio.2018.01.009DOI Listing
April 2018

Altered regulation and expression of genes by BET family of proteins in COPD patients.

PLoS One 2017 1;12(3):e0173115. Epub 2017 Mar 1.

AstraZeneca, Respiratory, Inflammation and Autoimmunity iMed, Pepparedsleden 1, Mölndal, Sweden.

Background: BET proteins (BRD2, BRD3, BRDT and BRD4) belong to the family of bromodomain containing proteins, which form a class of transcriptional co-regulators. BET proteins bind to acetylated lysine residues in the histones of nucleosomal chromatin and function either as co-activators or co-repressors of gene expression. An imbalance between HAT and HDAC activities resulting in hyperacetylation of histones has been identified in COPD. We hypothesized that pan-BET inhibitor (JQ1) treatment of BET protein interactions with hyperacetylated sites in the chromatin will regulate excessive activation of pro-inflammatory genes in key inflammatory drivers of alveolar macrophages (AM) in COPD.

Methods And Findings: Transcriptome analysis of AM from COPD patients indicated up-regulation of macrophage M1 type genes upon LPS stimulation. Pan-BET inhibitor JQ1 treatment attenuated expression of multiple genes, including pro-inflammatory cytokines and regulators of innate and adaptive immune cells. We demonstrated for the first time that JQ1 differentially modulated LPS-induced cytokine release from AM or peripheral blood mononuclear cells (PBMC) of COPD patients compared to PBMC of healthy controls. Using the BET regulated gene signature, we identified a subset of COPD patients, which we propose to benefit from BET inhibition.

Conclusions: This work demonstrates that the effects of pan-BET inhibition through JQ1 treatment of inflammatory cells differs between COPD patients and healthy controls, and the expression of BET protein regulated genes is altered in COPD. These findings provide evidence of histone hyperacetylation as a mechanism driving chronic inflammatory changes in COPD.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0173115PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5332090PMC
August 2017

Combining evidence of preferential gene-tissue relationships from multiple sources.

PLoS One 2013 12;8(8):e70568. Epub 2013 Aug 12.

Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden.

An important challenge in drug discovery and disease prognosis is to predict genes that are preferentially expressed in one or a few tissues, i.e. showing a considerably higher expression in one tissue(s) compared to the others. Although several data sources and methods have been published explicitly for this purpose, they often disagree and it is not evident how to retrieve these genes and how to distinguish true biological findings from those that are due to choice-of-method and/or experimental settings. In this work we have developed a computational approach that combines results from multiple methods and datasets with the aim to eliminate method/study-specific biases and to improve the predictability of preferentially expressed human genes. A rule-based score is used to merge and assign support to the results. Five sets of genes with known tissue specificity were used for parameter pruning and cross-validation. In total we identify 3434 tissue-specific genes. We compare the genes of highest scores with the public databases: PaGenBase (microarray), TiGER (EST) and HPA (protein expression data). The results have 85% overlap to PaGenBase, 71% to TiGER and only 28% to HPA. 99% of our predictions have support from at least one of these databases. Our approach also performs better than any of the databases on identifying drug targets and biomarkers with known tissue-specificity.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0070568PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3741196PMC
March 2014

Deletion of skeletal muscle SOCS3 prevents insulin resistance in obesity.

Diabetes 2013 Jan 6;62(1):56-64. Epub 2012 Sep 6.

St. Vincent’s Institute of Medical Research and Department of Medicine, University of Melbourne, Fitzroy, Victoria, Australia.

Obesity is associated with chronic low-grade inflammation that contributes to defects in energy metabolism and insulin resistance. Suppressor of cytokine signaling (SOCS)-3 expression is increased in skeletal muscle of obese humans. SOCS3 inhibits leptin signaling in the hypothalamus and insulin signal transduction in adipose tissue and the liver. Skeletal muscle is an important tissue for controlling energy expenditure and whole-body insulin sensitivity; however, the physiological importance of SOCS3 in this tissue has not been examined. Therefore, we generated mice that had SOCS3 specifically deleted in skeletal muscle (SOCS MKO). The SOCS3 MKO mice had normal muscle development, body mass, adiposity, appetite, and energy expenditure compared with wild-type (WT) littermates. Despite similar degrees of obesity when fed a high-fat diet, SOCS3 MKO mice were protected against the development of hyperinsulinemia and insulin resistance because of enhanced skeletal muscle insulin receptor substrate 1 (IRS1) and Akt phosphorylation that resulted in increased skeletal muscle glucose uptake. These data indicate that skeletal muscle SOCS3 does not play a critical role in regulating muscle development or energy expenditure, but it is an important contributing factor for inhibiting insulin sensitivity in obesity. Therapies aimed at inhibiting SOCS3 in skeletal muscle may be effective in reversing obesity-related glucose intolerance and insulin resistance.
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http://dx.doi.org/10.2337/db12-0443DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3526029PMC
January 2013

Policy measures and the survival of foster infants in Stockholm 1878-1925.

Eur J Public Health 2012 Feb 13;22(1):56-60. Epub 2011 Feb 13.

Centre for Health Equity Studies, Karolinska Institutet, Stockholm University, SE 106 93 Stockholm, Sweden.

Background: At the end of the 19th century, infant mortality was high in urban and rural areas in Sweden. In Stockholm, the mortality rate was particularly high among foster children. This study addresses the importance for health of targeted public policies and their local implementation in the reduction of excess mortality among foster children in Stockholm at the turn of the 19th century. In response to public concern, a law was passed in 1902 on inspections of foster homes. Stockholm city employed a handful of inspectors who visited foster homes and advised parents on child care and feeding.

Methods: Analysis of historical records from the City of Stockholm was combined with epidemiological analysis of mortality rates and hazard ratios on individual-level data for 112, 746 children aged <1 year residing in one part of Stockholm between 1878 and 1925. Hazard ratios of mortality were calculated using Cox' regression analysis.

Results: Mortality rates of foster infants exceeded 300/1000 before 1903. Ten years later the mortality rates among foster children had declined and were similar to other children born in and out of wedlock. Historical accounts and epidemiological analysis of individual-level data over a longer time period showed similar results.

Conclusions: Targeted policy measures to foster children may have potentiated the positive health effects of other universal policies, such as improved living conditions, clean water and sanitation for the whole population in the city, contributing to an equalization of mortality rates between different groups.
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http://dx.doi.org/10.1093/eurpub/ckr002DOI Listing
February 2012

Characterization of species-related differences in the pharmacology of tachykinin NK receptors 1, 2 and 3.

Biochem Pharmacol 2009 May 6;77(9):1522-30. Epub 2009 Feb 6.

Department of Bioscience, AstraZeneca R&D, Mölndal, Sweden.

Tachykinin NK receptors (NKRs) differ to a large degree among species with respect to their affinities for small molecule antagonists. The aims of the present study were to clone NKRs from gerbil (NK2R and NK3R) and dog (NK1R, NK2R and NK3R) in which the sequence was previously unknown and to investigate the potency of several NKR antagonists at all known human, dog, gerbil and rat NKRs. The NKR protein coding sequences were cloned and expressed in CHO cells. The inhibitory concentrations of selective and non-selective NKR antagonists were determined by inhibition of agonist-induced mobilization of intracellular Ca2+. Receptor homology models were constructed based on the rhodopsin crystal structure to investigate and identify the antagonist binding sites and interaction points in the transmembrane (TM) regions of the NKRs. Data collected using the cloned dog NK1R confirmed that the dog NK1R displays similar pharmacology as the human and the gerbil NK1R, but differs greatly from the mouse and the rat NK1R. Despite species-related amino acid (AA) differences located close to the antagonist binding pocket of the NK2R, they did not affect the potency of the antagonists ZD6021 and saredutant. Two AA differences located close to the antagonist binding site of NK3R likely influence the NK3R antagonist potency, explaining the 3-10-fold decrease in potency observed for the rat NK3R. For the first time, detailed pharmacological experiments in vitro with cloned NKRs demonstrate that not only human, but also dog and gerbil NKR displays similar antagonist pharmacology while rat diverges significantly with respect to NK1R and NK3R.
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http://dx.doi.org/10.1016/j.bcp.2009.01.020DOI Listing
May 2009

Ontology-based interactive information extraction from scientific abstracts.

Comp Funct Genomics 2005 ;6(1-2):67-71

Linguamatics Ltd, St. John's Innovation Centre, Cambridge CB4 0WS, UK.

Over recent years, there has been a growing interest in extracting information automatically or semi-automatically from the scientific literature. This paper describes a novel ontology-based interactive information extraction (OBIIE) framework and a specific OBIIE system. We describe how this system enables life scientists to make ad hoc queries similar to using a standard search engine, but where the results are obtained in a database format similar to a pre-programmed information extraction engine. We present a case study in which the system was evaluated for extracting co-factors from EMBASE and MEDLINE.
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http://dx.doi.org/10.1002/cfg.456DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2448603PMC
June 2010

The dialectics of childhood diarrhea mortality.

Int J Health Serv 2006 ;36(3):481-501

Department of Public Health Sciences, Karolinska Institute, Stockholm, Sweden.

As in European countries a century ago, diarrhea is a major cause of child mortality in poor countries today. In Stockholm at the turn of the 19th century, political commitment, infrastructural investments in water and sanitation, and enforcement of sanitary improvements by a strong implementing organization helped eliminate diarrhea as a principal cause of death among children. These interventions also had an equitable impact on social class differences in diarrhea mortality, but not on overall mortality; overall mortality declined, but class differences remained. General infrastructural improvement and health education coupled with targeted interventions to vulnerable children may be successful in improving child health and reducing social differentials in mortality. Specific health care interventions may need to be complemented by infrastructural investments to improve water and sanitation if diarrhea mortality is to be further reduced in poor countries today.
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http://dx.doi.org/10.2190/EPEY-MQ53-G6P0-RM30DOI Listing
January 2007

Equitable child health interventions: the impact of improved water and sanitation on inequalities in child mortality in Stockholm, 1878 to 1925.

Am J Public Health 2005 Feb;95(2):208-16

Department of Public Health Sciences, Division of Social Medicine, Karolinska Institutet, SE-171 76 Stockholm, Sweden.

Today, many of the 10 million childhood deaths each year are caused by diseases of poverty--diarrhea and pneumonia, for example, which were previously major causes of childhood death in many European countries. Specific analyses of the historical decline of child mortality may shed light on the potential equity impact of interventions to reduce child mortality. In our study of the impact of improved water and sanitation in Stockholm from 1878 to 1925, we examined the decline in overall and diarrhea mortality among children, both in general and by socioeconomic group. We report a decline in overall mortality and of diarrhea mortality and a leveling out of socioeconomic differences in child mortality due to diarrheal diseases, but not of overall mortality. The contribution of general and targeted policies is discussed.
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http://dx.doi.org/10.2105/AJPH.2003.034900DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1449154PMC
February 2005