| 1. |
- Barbe, Laurent, et al.
(author)
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Toward a confocal subcellular atlas of the human proteome
- 2008
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In: Molecular and cellular proteomics. - 1535-9476 .- 1535-9484. ; 7:3, s. 499-508
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Journal article (peer-reviewed)abstract
- Information on protein localization on the subcellular level is important to map and characterize the proteome and to better understand cellular functions of proteins. Here we report on a pilot study of 466 proteins in three human cell lines aimed to allow large scale confocal microscopy analysis using protein-specific antibodies. Approximately 3000 high resolution images were generated, and more than 80% of the analyzed proteins could be classified in one or multiple subcellular compartment(s). The localizations of the proteins showed, in many cases, good agreement with the Gene Ontology localization prediction model. This is the first large scale antibody-based study to localize proteins into subcellular compartments using antibodies and confocal microscopy. The results suggest that this approach might be a valuable tool in conjunction with predictive models for protein localization.
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| 2. |
- Al-Anati, Lauy, et al.
(author)
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Hydroxyl metabolite of PCB 180 induces DNA damage signaling and enhances the DNA damaging effect of benzo[a]pyrene
- 2015
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In: Chemico-Biological Interactions. - : Elsevier. - 0009-2797 .- 1872-7786. ; 239, s. 164-173
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Journal article (peer-reviewed)abstract
- Non-dioxin-like (NDL) polychlorinated biphenyls (PCBs) and their hydroxyl metabolites (OH-PCBs) are ubiquitous environmental contaminants in human tissues and blood. The toxicological impact of these metabolites is poorly understood. In this study rats were exposed to ultrapure PCB180 (10-1000 mg/kg bw) for 28 days and induction of genotoxic stress in liver was investigated. DNA damage signaling proteins (pChk1Ser317 and gamma H2AXSer319) were increased dose dependently in female rats. This increase was paralleled by increasing levels of the metabolite 3'-OH-PCB180. pChk1 was the most sensitive marker. In in vitro studies HepG2 cells were exposed to 1 mu M of PCB180 and 3'-OH-PCB180 or the positive control benzo[a]pyrene (BaP, 5 mu M). 3'-OH-PCB180, but not PCB180, induced CYP1A1 mRNA and gamma H2AX. CYP1A1 mRNA induction was seen at 1 h, and gamma H2AX at 3 h. The anti-oxidant N-Acetyl-L-Cysteine (NAC) completely prevented, and 17 beta-estradiol amplified the gamma H2AX induction by 3'-OH-PCB180. As 3'-OH-PCB180 induced CYP1A1, a major BaP-metabolizing and activating enzyme, interactions between 3'-OH-PCB180 and BaP was also studied. The metabolite amplified the DNA damage signaling response to BaP. In conclusion, metabolism of PCB180 to its hydroxyl metabolite and the subsequent induction of CYP1A1 seem important for DNA damage induced by PCB180 in vivo. Amplification of the response with estradiol may explain why DNA damage was only seen in female rats.
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| 3. |
- Broström, Julia, et al.
(author)
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Toluene diisocyanate: Induction of the autotaxin-lysophosphatidic acid axis and its association with airways symptoms.
- 2015
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In: Toxicology and Applied Pharmacology. - : Elsevier BV. - 1096-0333 .- 0041-008X. ; 287:3, s. 222-231
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Journal article (peer-reviewed)abstract
- Diisocyanates are industrial chemicals which have a wide range of applications in developed and developing countries. They are notorious lung toxicants and respiratory sensitizers. However, the mechanisms behind their adverse effects are not adequately characterized. Autotaxin (ATX) is an enzyme producing lysophosphatidic acid (LPA), and the ATX-LPA axis has been implicated in lung related inflammatory conditions and diseases, including allergic asthma, but not to toxicity of environmental low-molecular-weight chemicals. We investigated effects of toluene diisocyanate (TDI) on ATX induction in human lung epithelial cell models, and we correlated LPA-levels in plasma to biomarkers of TDI exposure in urine collected from workers exposed to <5ppb (parts per billion). Information on workers' symptoms was collected through interviews. One nanomolar TDI robustly induced ATX release within 10min in vitro. A P2X7- and P2X4-dependent microvesicle formation was implicated in a rapid ATX release and a subsequent protein synthesis. Co-localization between purinergic receptors and ATX was documented by immunofluorescence and confocal microscopy. The release was modulated by monocyte chemoattractant protein-1 (MCP-1) and by extracellular ATP. In workers, we found a dose-response relationship between TDI exposure biomarkers in urine and LPA levels in plasma. Among symptomatic workers reporting "sneezing", the LPA levels were higher than among non-symptomatic workers. This is the first report indicating induction of the ATX-LPA axis by an environmental low-molecular-weight chemical, and our data suggest a role for the ATX-LPA axis in TDI toxicity.
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| 4. |
- Lundgren, Markus, et al.
(author)
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Analgesic antipyretic use among young children in the TEDDY study : No association with islet autoimmunity
- 2017
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In: BMC Pediatrics. - : Springer Science and Business Media LLC. - 1471-2431. ; 17:1
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Journal article (peer-reviewed)abstract
- Background: The use of analgesic antipyretics (ANAP) in children have long been a matter of controversy. Data on their practical use on an individual level has, however, been scarce. There are indications of possible effects on glucose homeostasis and immune function related to the use of ANAP. The aim of this study was to analyze patterns of analgesic antipyretic use across the clinical centers of The Environmental Determinants of Diabetes in the Young (TEDDY) prospective cohort study and test if ANAP use was a risk factor for islet autoimmunity. Methods: Data were collected for 8542 children in the first 2.5 years of life. Incidence was analyzed using logistic regression with country and first child status as independent variables. Holm's procedure was used to adjust for multiplicity of intercountry comparisons. Time to autoantibody seroconversion was analyzed using a Cox proportional hazards model with cumulative analgesic use as primary time dependent covariate of interest. For each categorization, a generalized estimating equation (GEE) approach was used. Results: Higher prevalence of ANAP use was found in the U.S. (95.7%) and Sweden (94.8%) compared to Finland (78.1%) and Germany (80.2%). First-born children were more commonly given acetaminophen (OR 1.26; 95% CI 1.07, 1.49; p = 0.007) but less commonly Non-Steroidal Anti-inflammatory Drugs (NSAID) (OR 0.86; 95% CI 0.78, 0.95; p = 0.002). Acetaminophen and NSAID use in the absence of fever and infection was more prevalent in the U.S. (40.4%; 26.3% of doses) compared to Sweden, Finland and Germany (p < 0.001). Acetaminophen or NSAID use before age 2.5 years did not predict development of islet autoimmunity by age 6 years (HR 1.02, 95% CI 0.99-1.09; p = 0.27). In a sub-analysis, acetaminophen use in children with fever weakly predicted development of islet autoimmunity by age 3 years (HR 1.05; 95% CI 1.01-1.09; p = 0.024). Conclusions: ANAP use in young children is not a risk factor for seroconversion by age 6 years. Use of ANAP is widespread in young children, and significantly higher in the U.S. compared to other study sites, where use is common also in absence of fever and infection.
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| 5. |
- Prestjan, Anna, 1971-
(author)
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Att bota en drinkare : idéer och praktik i svensk alkoholistvård 1885 - 1916
- 2004
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Doctoral thesis (other academic/artistic)abstract
- The focus for this thesis is the alcoholic care in Sweden from the establishment of the first alcoholic institution in 1885 and the years right after the compulsory care act was passed in 1913. In the thesis the practical activity at the four first alcoholic institutions is examined, but also the ideas concerning alcoholic care that were formulated by the men that were the institutions initiators and responsible for the activities.The research has its starting point in and also confirms care as a sociocultural phenomenon and not merely a medical issue, and that there is an agreement in terms of meaning between the ideals expressed by the medicine as well as other societal interests. Both idea and actual practice have been examined in order to answer the question how the alcoholic care was shaped as a result of the medicalization of the drunkenness problem, but also the consequences of this alcoholic care. Especially the American and the British research position has proved that conceptions about will and morals have been significant to the shaping of a care ideology concerning the alcoholism and its treatment. A second question the research has intended to answer is if, an if then how, such conceptions affected the care ideology and the actual care in practice also in Sweden.One of the results of this thesis is that the early alcoholic care in Sweden ideologically claimed to represent and originate from medical principles and knowledge, even though the treatment methods proposed and practiced originated from the conception about alcoholism as a willpower illness. The purpose with the treatment was primarily to affect the will and moral and consequently the traditional medical science and pharmaceutics were given a subordinated position compared to the medical methods that proceeded from a holistic view on the human, as for example hypnosis and water therapy. The treatment was also individualized according to a relation between the doctor and each patient.The examinations confirm the alcoholic care as a sociocultural phenomenon that aimed at and resulted in functions where medical interests coincided with those of the society in general. This is shown by the fact that treatment methods as well as the aim with the alcoholic’s treatment were the same at those kinds of institutions with a medical starting point as well as at the Floda colonies, in spite of the fact that the latter was an alcoholic institution that dismissed alcoholism as a medical issue.The first alcoholic institutions functioned as improvement machines, where alcoholics regarded as bad for the society were pressed in at the one end, to in the other come out as ideal men and citizens - hard working family men, self-controlled and physically powerful. With these ideals medical definitions of health coincided with social definitions of the meaning of being a worthy citizen.Among the foremost consequences of the first alcoholic care was the presentation of an alternative solution on the societal problem drunkenness and an optimistic belief in the alcoholic’s potential to be cured. Other consequences were the ones that concerned the individual – a state of illness will result in changes in the individual’s status in society and that the ill person has to admit to be the deviating one that is to be corrected. On the side of the therapeutical function, the first alcoholic care also had a normative function, though only within the social class that the heads at the institutions themselves belonged to. The alcoholic care was during this period accordingly not an expression for the upper classes’ social control of the lower classes, but rather a self improvement project by the middle class. Finally the alcoholic care during the examined period also had consequences for the later alcoholic care. During the period 1885 – about 1916 the practical experiences made lead to a revision of the care ideology. A private alcoholic care for volunteering patients was still the principle, but in reality an increased state involvement as well as force could be motivated.
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| 6. |
- Stenius, Ivan, 1972-, et al.
(author)
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A system for autonomous seaweed farm inspection with an underwater robot
- 2022
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In: Sensors. - : MDPI AG. - 1424-8220. ; 22:13
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Journal article (peer-reviewed)abstract
- This paper outlines challenges and opportunities in operating underwater robots (so-called AUVs) on a seaweed farm. The need is driven by an emerging aquaculture industry on the Swedish west coast where large-scale seaweed farms are being developed. In this paper, the operational challenges are described and key technologies in using autonomous systems as a core part of the operation are developed and demonstrated. The paper presents a system and methods for operating an AUV in the seaweed farm, including initial localization of the farm based on a prior estimate and dead-reckoning navigation, and the subsequent scanning of the entire farm. Critical data from sidescan sonars for algorithm development are collected from real environments at a test site in the ocean, and the results are demonstrated in a simulated seaweed farm setup.
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