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  • 301.
    Fredriksson, Anders
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Eriksson, Per
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    The NMDA antagonist MK-801 potentiates apoptosis in the neonatal mouse brain, leading to hyperactivity and learning disabilities in adult mice2002In: The Toxicologist, 2002, p. 120-Conference paper (Refereed)
  • 302.
    Fredriksson, Anders
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Eriksson, Per
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology. Avd för ekotoxikologi.
    Archer, T
    Postnatal iron-induced motor behaviour alterations following chronic neuroleptic administration in mice.2006In: J Neural Transm, ISSN 0300-9564, Vol. 113, no 2, p. 137-50Article in journal (Refereed)
  • 303.
    Fredriksson, Anders
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Pontén, E
    Gordh, T
    Eriksson, Per
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Exposure to ketamine during neonatal life induces triggered apoptotic neurogeneration and behavioural deficits in adulthood2005In: Toxicologist 84, 2005, p. 1073-Conference paper (Refereed)
  • 304.
    Fredriksson, Anders
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, Ulleråker, University Hospital.
    Pontén, Emma
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Gordh, Torsten
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
    Eriksson, Per
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology.
    Neonatal exposure to a combination of N-Methyl-D-aspartate and γ-aminobutyric acid type A receptor anesthetic agents potentiates apoptotic neurodegeneration and persistent behavioral deficits2007In: Anesthesiology, ISSN 0003-3022, E-ISSN 1528-1175, Vol. 107, no 3, p. 427-436Article in journal (Refereed)
    Abstract [en]

    Background: During the brain growth spurt, the brain develops and modifies rapidly. In rodents this period is neonatal, spanning the first weeks of life, whereas in humans it begins during the third trimester and continues 2 yr. This study examined whether different anesthetic agents, alone and in combination, administered to neonate mice, can trigger apoptosis and whether behavioral deficits occur later in adulthood.

    Methods: Ten-day-old mice were injected subcutaneously with ketamine (25 mg/kg), thiopental (5 mg/kg or 25 mg/kg), propofol (10 mg/kg or 60 mg/kg), a combination of ketamine (25 mg/kg) and thiopental (5 mg/kg), a combination of ketamine (25 mg/kg) and propofol (10 mg/kg), or control (saline). Fluoro-Jade staining revealed neurodegeneration 24 h after treatment. The behavioral tests-spontaneous behavior, radial arm maze, and elevated plus maze (before and after anxiolytic)-were conducted on mice aged 55-70 days.

    Results: Coadministration of ketamine plus propofol or ketamine plus thiopental or a high dose of propofol alone significantly triggered apoptosis. Mice exposed to a combination of anesthetic agents or ketamine alone displayed disrupted spontaneous activity and learning. The anxiolytic action of diazepam was less effective when given to adult mice that were neonatally exposed to propofol.

    Conclusion: This study shows that both a γ-aminobutyric acid type A agonist (thiopental or propofol) and an N-methyl-d-aspartate antagonist (ketamine) during a critical stage of brain development potentiated neonatal brain cell death and resulted in functional deficits in adulthood. The use of thiopental, propofol, and ketamine individually elicited no or only minor changes.

  • 305.
    Fredriksson, Anders
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Schröder, N.
    Eriksson, Per
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Izquierdo, I.
    Archer, T.
    Neonatal iron potentiates adult MPTP-induced neurodegenerative and functional deficits.2001In: Parkinsonism Relat Disord, ISSN 1353-8020, Vol. 7, no 2, p. 97-105Article in journal (Refereed)
  • 306. Friedman, Matt
    et al.
    Blom, Henning
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Evolutionary Organism Biology. Evolutionär organismbiologi.
    A new actinopterygian from the Famennian of East Greenland and the interrelationship on Devonian ray-finned fishes2006In: Journal of Paleontology, Vol. 80, no 6, p. 1186-1204Article in journal (Refereed)
  • 307. Friedman, Matt
    et al.
    Blom, Henning
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Evolutionary Organism Biology.
    A new actinopterygian from the Famennian of East Greenland and the interrelationships of Devonian ray-finned fishes2006In: Journal of Paleontology, ISSN 0022-3360, E-ISSN 1937-2337, Vol. 80, no 6, p. 1186-1204Article, review/survey (Refereed)
    Abstract [en]

    A new actinopterygian, Cuneognathus gardineri new genus and species, is described from the Devonian (Famennian) Obrutschew Bjerg Formation of East Greenland on the basis of multiple incomplete specimens. Cuneognathus most closely resembles Limnomis from the Famennian Catskill Formation of Pennsylvania, and, like that taxon, is known exclusively from freshwater deposits. A cladistic analysis with an ingroup of 13 actinopterygians and an outgroup of five sarcopterygians explores the relationships between the new genus and some of its better-known Devonian contemporaries, and recovers the same four topologies regardless of the implementation of limited character ordering. Cheirolepis is resolved as the most basal of well-known Devonian actinopterygians, consistent with a majority of previous studies. A novel sister-group relationship between Howqualepis and Tegeolepis is found in all trees. Disagreement between the most parsimonious cladograms is concentrated in a clade whose members are often informally referred to as 'stegotrachelids.' Cuneognathus and Limnomis are resolved as sister taxa within this large radiation along with the pairings of Moythomasia dugaringa plus M. nitida and Krasnoyarichtkys plus Stegotrachelus. The arrangement of taxa is conserved when the enigmatic Dialipina is added to the analysis, although the reconstructed position of that genus above both Cheirolepis and Osorioichthys seems improbable. Our scheme of relationships suggests that actinopterygians invaded freshwater environments at least four times during the Devonian, while age constraints indicate that many of the cladogenic events between ingroup taxa included in this study occurred during or before the Givetian.

  • 308. Friedman, Matt
    et al.
    Blom, Henning
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Evolutionary Organism Biology. Evolutionär organismbiologi.
    Setting the stage for half of vertebrate diversity: the Devonian history of actinopterygians.2005In: PaleoBios, ISSN 0031-0298, Vol. 25, no 2 (supplement), p. 47-Article in journal (Other scientific)
  • 309. Friedman, Matt
    et al.
    Brazeau, Martin
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Evolutionary Organism Biology.
    A reappraisal of the origin and basal radiation of the Osteichthyes2010In: Journal of Vertebrate Paleontology, ISSN 0272-4634, E-ISSN 1937-2809, Vol. 30, no 1, p. 36-56Article in journal (Refereed)
    Abstract [en]

    The earliest Actinoptergyii (ray-finned fishes) and Sarcopterygii (lobe-finned fishes) have been studied intensely, and a consistent picture of interrelationships has begun to emerge for the latter. In contrast, there has been minimal documentation of the pattern of character acquisition leading to the osteichthyan crown. We review the synapomorphies proposed for various levels within osteichthyan phylogeny (total group; Acanthodes + crown group; crown group; Sarcoptergyii; Actinopterygii), confirming some, rejecting others, and making new additions. This distribution of characters is used to interpret the placement of problematic Siluro-Devonian genera traditionally assigned to Actinopterygii, and suggests these taxa are stem osteichthyans. Earlier placements of these forms within the crown are symptomatic of taxonomies based on unpolarized similarities rather than synapomorphies.

  • 310. Friedman, Matt
    et al.
    Brazeau, Martin
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Evolutionary Organism Biology.
    Placoderm muscles and chordate interrelationships2008In: Biology Letters, Vol. 4, p. 103-Article in journal (Refereed)
  • 311.
    Frisk, Åsa M.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology. Paleobiologi.
    Ebbestad, Jan Ove R.
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences. Paleobiologi.
    Biostratigraphy of an Early Ordovician (Tremadoc) epicontinental carbonate facies: the Baltoscandian Bjørkåsholmen Formation2006In: Geological Society of America Abstracts with Programs, 2006, p. 551-551Conference paper (Other (popular science, discussion, etc.))
    Abstract [en]

    The Lower Ordovician in Baltoscandia was initiated by extensive carbonate deposition forming the Tremadoc Bjørkåsholmen Formation (formerly the Ceratopyge Limestone), a distinctive unit corresponding to the Apatokephalus serratus trilobite Zone. The unit is remarkable in its near homogenous facies, lithologic and faunal composition throughout the Baltoscandian platform, representing a shallow water epicontinental environment. Similar facies are recognized in the autochthonic Caledonides believed to have been deposited 400 km to the west of the present Norwegian shoreline, while the easternmost outcrops are found on the island Öland off the east coast of Sweden. This gives an east-west extension of nearly 2000 kilometres, while the north-south extension is less well known owing to lack of exposures. However, glauconitic sandstones replace the carbonates both in the Siljan District of Dalarna, Sweden, and in the easternmost baltoscandian platform in Estonia and the St. Petersburg area of Russia. Trilobites are the dominant fossil group, with 36 species belonging to 26 genera. For the ongoing study of trilobite biostratigraphy of the unit, the trilobite abundance distribution has been investigated for two localities on southern Öland, Sweden. In both investigated sections the resulting abundance distributions are consistent, with diversity declining upward. The abundancy distribution compares in detail with several sections studied earlier from the Oslo Region of Norway. A section in Västergötland, halfway between the Oslo Region and Öland, is currently also under study. However, preliminary comparison across the Baltoscandian platform between the Oslo Region and Öland, suggests an extensive stable environment and fauna during deposition of the Bjørkåsholmen Formation.

  • 312.
    Gambäck Keyser, Pia
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Comparative Physiology. Jämförande fysiologi.
    Structure and localisation of some immune proteins in freshwater crayfish1995Licentiate thesis, monograph (Other scientific)
  • 313.
    Gao, Kai
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Brandt, Ingvar
    Jönsson, Maria
    Cloning, and expression of cytochrome P450 1A, 1B and 1C genes in liver, brain, gill, and kidney from PCB 126-exposed three.spined stickleback (Gasterosteus aculeatus L.)2009In: Organohalogen Compounds, 2009, p. 2485-2489Conference paper (Refereed)
  • 314.
    Glynn, Anders
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Aune, Marie
    Darnerud, Per Ola
    Cnattingius, Sven
    Bjerselius, Rickard
    Becker, Wulf
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Clinical Nutrition and Metabolism.
    Lignell, Sanna
    Determinants of serum concentrations of organochlorine compounds in Swedish pregnant women: a cross-sectional study2007In: Environmental health, ISSN 1476-069X, E-ISSN 1476-069X, Vol. 6, p. 2-Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: We performed a cross-sectional study of associations between personal characteristics and lipid-adjusted serum concentrations of certain PCB congeners and chlorinated pesticides/metabolites among 323 pregnant primiparous women from Uppsala County (age 18-41 years) sampled 1996-1999. METHODS: Extensive personal interviews and questionnaires about personal characteristics were performed both during and after pregnancy. Concentrations of organochlorine compounds in serum lipids in late pregnancy were analysed by gas chromatography. Associations between personal characteristics and serum levels of organochlorine compounds were analysed by multiple linear regression. RESULTS: Participation rate was 82% (325 of 395 women). Serum concentrations of PCB congeners IUPAC no. 28, 52, 101, 105 and 167, and o, p'-DDT and -DDE, p, p'-DDT and -DDD, oxychlordane, and gamma- and alpha-HCH were in many cases below the limit of quantification (LOQ). No statistical analysis of associations with personal characteristics could be performed for these substances. Concentrations of PCB congeners IUPAC no. 118, 138, 153, 156 and 180, HCB, beta-HCH, trans-nonachlor and p, p'-DDE increased with increased age and were highest in women sampled early during the 4 year study period. This shows that older women and women sampled early in the study had experienced the highest life-time exposure levels, probably mainly during childhood and adolescence. The importance of early exposures was supported by lower PCB concentrations and higher beta-HCH and p, p'-DDE concentrations among women born in non-Nordic countries. Moreover, serum concentrations of certain PCBs and pesticide/metabolites were positively associated with consumption of fatty fish during adolescence, and concentrations of CB 156, CB 180 and p, p'-DDE increased significantly with number of months women had been breast-fed during infancy. Short-term changes in bodily constitution may, however, also influence serum concentrations, as suggested by negative associations between concentrations of organochlorine compounds and BMI before pregnancy and weight change during pregnancy. CONCLUSION: Although some of the associations could be caused by unknown personal characteristics confounding the results, our findings suggest that exposures to organochlorine compounds during childhood and adolescence influence the body burdens of the compounds during pregnancy.

  • 315.
    Glynn, Anders
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Aune, Marie
    Nilsson, Ingrid
    Darnerud, Per Ola
    Ankarberg, Emma Halldin
    Bignert, Anders
    Nordlander, Ingrid
    Declining levels of PCB, HCB and p,p'-DDE in adipose tissue from food producing bovines and swine in Sweden 1991-20042009In: Chemosphere, ISSN 0045-6535, E-ISSN 1879-1298, Vol. 74, no 11, p. 1457-1462Article in journal (Refereed)
    Abstract [en]

    The official control programme for organochlorine (OC) contaminants in food producing animals in Sweden was used to study temporal and spatial trends of the polychlorinated biphenyl CB 153, hexachlorobenzene (HCB) and p,p'-DDE in adipose tissue from bovines and swine 1991-2004. Our results show that efforts to decrease OC contamination of animal feed and the environment have had a positive impact on the contamination of the animal production. OC concentrations declined significantly in almost all studied regions of Sweden. OC temporal trends were slower in bovines (6-8% per year) than in swine (10-12%). Power analyses showed that data from more than 10 years of sampling were needed for a detection of an annual OC level change of 5% in both species in the control programme, due to large within- and between-year variation in OC levels. CB 153 and p,p'-DDE levels were higher in southern than in northern Sweden. Levels decreased with age in milk cows, but not in young nulliparous cows (heifers) and bulls. Moreover, milk cows and bulls had significantly lower OC levels than heifers. Levels were not age-dependent among swine, but castrated male swine (barrows) had significantly lower OC levels than young female swine (gilts). Levels of the studied OCs are now in many cases below the LOQ of the analytical method used. Future time trend studies of these OCs thus depend on lowered LOQs in the control programme.

  • 316.
    Glynn, Anders
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Aune, Marie
    Nilsson, Ingrid
    Darnerud, Per Ola
    Ankarberg, Emma Halldin
    Nordlander, Ingrid
    Bignert, Anders
    Reply to comments of Jose G. Dorea on "Declining levels of PCB, HCB and p,p '-DDE in adipose tissue from food producing bovines and swine in Sweden 1991-2004" by Glynn et al. [Chemosphere 74(11)(2009)1457-1462]2009In: Chemosphere, ISSN 0045-6535, E-ISSN 1879-1298, Vol. 76, no 6, p. 868-868Article in journal (Refereed)
  • 317.
    Glynn, Anders W
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Atuma, S
    Aune, M
    Darnerud, P O
    Cnattingius, S
    Polychlorinated biphenyl congeners as markers of toxic equivalents of polychlorinated biphenyls, dibenzo-p-dioxins and dibenzofurans in breast milk.2001In: Environ Res, ISSN 0013-9351, Vol. 86, no 3, p. 217-28Article in journal (Refereed)
  • 318.
    Glynn, Anders W
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Sparén, A
    Danielsson, L G
    Sundström, B
    Jorhem, L
    The influence of complexing agents on the solubility and absorption of aluminium in rats exposed to aluminium in water.2001In: Food Addit Contam, ISSN 0265-203X, Vol. 18, no 6, p. 515-23Article in journal (Refereed)
  • 319.
    Glynn, Anders Wicklund
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Granath, Fredrik
    Aune, Marie
    Atuma, Samuel
    Darnerud, Per Ola
    Bjerselius, Rickard
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Vainio, Harri
    Weiderpass, Elisabete
    Organochlorines in Swedish women: determinants of serum concentrations.2003In: Environ Health Perspect, ISSN 0091-6765, Vol. 111, no 3, p. 349-55Article in journal (Refereed)
  • 320.
    Glynn, AW
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    The influence of zinc on apical uptake of cadmium in the gills and cadmium influx to the circulatory system in zebrafish (Danio rerio)2001In: COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY, ISSN 1532-0456, Vol. 128, no 2, p. 165-172Article in journal (Refereed)
    Abstract [en]

    Zn (0-16 muM) effects on apical Cd uptake from the water into the branchial epithelium and influx of Cd from the water to the circulatory system in zebrafish (Danio rerio) were studied in three experiments. Apical Cd uptake was decreased by Zn in all thre

  • 321. Goldstone, J. V.
    et al.
    Jönsson, Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Behrendt, L.
    Woodin, B. R.
    Jenny, M. J.
    Nelson, D. R.
    Stegeman, J. J.
    Cytochrome P450 1D1: A novel CYP1A-related gene that is not transcriptionally activated by PCB126 or TCDD2009In: Archives of Biochemistry and Biophysics, ISSN 0003-9861, E-ISSN 1096-0384, Vol. 482, no 1-2, p. 7-16Article in journal (Refereed)
    Abstract [en]

    Enzymes in the cytochrome P450 1 family oxidize many common environmental toxicants. We identified a new CYP1, termed CYP1D1, in zebrafish. Phylogenetically, CYP1D1 is paralogous to CYP1A and the two share 45% amino acid identity and similar gene structure. In adult zebrafish, CYP1D1 is most highlyexpressed in liver and is relatively highly expressed in brain. CYP1D1 transcript levels were higher at 9 h post-fertilization than at later developmental times. Treatment of zebrafish with potent aryl hydrocarbon receptor (AHR) agonists (3,3',4,4',5-pentachlorobiphenyl or 2,3,7,8-tetrachlorodibenzo-p-dioxin) did not induce CYP1D1 transcript expression. Morpholino oligonucleotide knockdown of AHR2, which mediates induction of other CYP1s, did not affect CYP1D1 expression. Zebrafish CYP1D1 heterologously expressed in yeast exhibited ethoxyresorufin- and methoxyresorufin-O-dealkylase activities. Antibodies against a CYP1D1 peptide specifically detected a single electrophoretically-resolved protein band in zebrafish liver microsomes, distinct from CYP1A. CYP1D1 in zebrafish is a CYP1A-like gene that could have metabolic functions targeting endogenous compounds.

  • 322.
    Granberg, Lizette
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Brunström, Björn
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Brandt, Ingvar
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Formation of benzo[a]pyrene and 7,12-dimethylbenz[a]anthracene adducts in vascular endothelia of cytochrome P4501A-induced chicken embryos.2003In: Environ Toxicol Chem, ISSN 0730-7268, Vol. 22, no 10, p. 2393-9Article in journal (Refereed)
  • 323.
    Granberg, Lizette
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Östergren, Anna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Brandt, Ingvar
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Brittebo, Eva B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    CYP1A1 and CYP1B1 in blood-brain interfaces: CYP1A1-dependent bioactivation of 7,12-dimethylbenz(a)anthracene in endothelial cells.2003In: Drug Metabolism And Disposition, ISSN 0090-9556, E-ISSN 1521-009X, Vol. 31, no 3, p. 259-265Article in journal (Refereed)
    Abstract [en]

    Immunohistochemistry and autoradiography were used to identify sites of the cytochrome P450 enzymes (P450) 1A1 and 1B1 expression and activation of 7,12-dimethylbenz(a)anthracene (DMBA), in the brain of rodents pretreated with the aryl hydrocarbon receptor (AhR) agonists beta-naphthoflavone (BNF), 3,3',4,4',5-pentachlorobiphenyl or vehicle. Immunohistochemistry revealed that CYP1A1 was preferentially induced in endothelial cells (EC) in the choroid plexus, in veins in the leptomeninges, and in cerebral veins of AhR agonist-pretreated mice. No induction occurred in cerebral capillary EC. In vehicle-treated mice no localization of CYP1A1 in EC was observed. CYP1B1 was expressed in smooth muscle cells of arteries in the leptomeninges, in cerebral arteries/arterioles and to a low extent in ependymal cells of AhR agonist- and vehicle-treated mice. No CYP1B1 was detected in capillary loops of the choroid plexus or in cerebral capillaries. Following administration of [(3)H]DMBA to BNF-pretreated mice, a marked irreversible binding in EC of the choroid plexus and of veins in the leptomeninges was observed but not in cerebral capillaries. In vehicle-treated mice, there was no [(3)H]DMBA-binding at these sites. Furthermore, a high level of irreversibly bound [(3)H]DMBA occurred in EC at these sites in precision-cut mouse/rat brain slices and in excised blood-brain interfaces incubated with [(3)H]DMBA. Since [(3)H]DMBA binding sites corresponded with the sites of CYP1A1 induction, we conclude that rodents express a constitutively low but highly inducible and functional CYP1A1 in EC of some of the blood-brain interfaces. The role of CYP1A1/1B1 and environmental pollutants in the etiology of cerebrovascular disease needs further consideration.

  • 324. Gu, H F
    et al.
    Lind, M I
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Comparative Physiology. Jämförande fysiologi.
    Wieslander, L
    Landegren, U
    Söderhäll, K
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Comparative Physiology. jämförande fysiologi.
    Melefors, O
    Using PRINS for gene mapping in polytene chromosomes.1997In: Chromosome Res, ISSN 0967-3849, Vol. 5, no 7, p. 463-5Article in journal (Refereed)
  • 325.
    Guibert, Sylvain
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Animal Development and Genetics.
    Zhao, Zhihu
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Animal Development and Genetics.
    Sjölinder, Mikael
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Animal Development and Genetics.
    Göndör, Anita
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Animal Development and Genetics.
    Fernandez, Alejandro
    Pant, Vinod
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Animal Development and Genetics.
    Ohlsson, Rolf
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Animal Development and Genetics.
    CTCF-binding sites within the H19 ICR differentially regulate local chromatin structures and cis-acting functions2012In: Epigenetics, ISSN 1559-2294, E-ISSN 1559-2308, Vol. 7, no 4, p. 361-369Article in journal (Refereed)
    Abstract [en]

    It is generally assumed that CTCF-binding sites are synonymous with the demarcation of expression domains by promoting the formation of chromatin loops. We have proposed earlier, however, that such features may be context-dependent. In support of this notion, we show here that chromatin loop structures, impinging on CTCF-binding sites 1/2 and 3/4 at the 5' and 3'-ends, respectively, within the maternal allele of the H19 imprinting control region (ICR), differ significantly. Although abrogation of CTCF binding to the maternal H19 ICR allele results in loss of chromatin loops in the 3'-region, there is a dramatic gain of long-range chromatin loops impinging on the 5'-region. As the degree of occupancy of its four CTCF-binding sites discriminates between the chromatin insulator and replication timing functions, we submit that the CTCF-binding sites within the H19 ICR are functionally diverse and organize context-dependent higher order chromatin conformations.

  • 326.
    Gustafsson, Magnus
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre.
    Toxicity studies on bone tissue from sheep grazing on a pasture treated with sewage sludge2008Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    In this study, femur bones and serum from rams and ewes (Ovis aries) bred on pastures fertilized twice annually with sewage sludge (2.25 tonnes dry matter/ha) or on control pastures were analysed. The control pastures was treated with conventional inorganic fertilizer. Both rams and ewes were exposed during development in utero, from conception, and after birth, during lactation, to weaning at 4 months of age. After that the rams were moved to pastures not fertilized with sewage sludge. The ewes, however, were retained on pastures treated with sewage sludge. The animals were slaughtered at 18 months of age and the femur bone was dissected. The peripheral Quantitative Computed Tomography (pQCT) and three-point bending test analyses of the femur bone were evaluated. In rams, the total bone mineral density (BMD) at the metaphyseal part of femur was significantly greater (10.5 %, p<0.05) in treated than control animals. Treated animals also exhibited a reduction in the total cross sectional area (CSA, 11.5 %, p<0.05), the trabecular CSA (17.1 %, p<0.05) and the periosteal circumference (5.7 %, p<0.05). Analysis of the mid-diaphyseal part revealed multiple effects e.g. the total BMD (13.8 %, p<0.05) increased significantly whereas the total CSA (12.1 %, p<0.05) and the marrow cavity (25.8 %, p<0.05) were significantly reduced in the treated rams. The threepoint bending test of the ram femur at the mid-diaphyseal part revealed an increased stiffness (6.4 %, p<0.05) in treated animals. In ewes, the trabecular bone mineral content (BMC) at the metaphyseal part of femur was significantly increased (41.6 %, p<0.05) in the treated ewes. pQCT analysis of the mid-diaphyseal part showed no adverse effects in the treated ewes. Femurs from treated ewes showed a reduction in the load at failure (17.3 %, p<0.05) and stiffness (10.7 %, p<0.05). The serum levels of the bone formation marker BAP, the bone resorption marker CTX and the vitamin D marker 25-OH D did not differ between exposed and control animals, neither for rams nor for ewes. In conclusion, this study shows that exposure to sewage sludge disrupt bone tissue homeostasis in sheep. As the rams were only exposed via placental transfer and mother’s milk, the obtained effects; increased cortical thickness, decreased circumference and decreased marrow cavity must be considered as developmental effects. The increase in femoral trabecular BMC in the ewes is thought likely to be attributable to estrogenic influences in the sludge.

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  • 327. Gutleb, Arno C.
    et al.
    Arvidsson, Dan
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Örberg, Jan
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Larsson, Sune
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Skaare, Janneche Utne
    Aleksandersen, Mona
    Ropstad, Erik
    Lind, Monica
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Occupational and Environmental Medicine.
    Effects on bone tissue in ewes (Ovies aries) and their foetuses exposed to PCB 118 and PCB 1532010In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 192, no 2, p. 126-133Article in journal (Refereed)
    Abstract [en]

    The aim of the present study was to investigate whether low levels of mono-ortho PCB 118 and di-ortho PCB 153, affect bone composition and strength in ewes (Dala breed) and their foetuses following exposure starting at conception and ending a week before expected delivery. In male foetuses, trabecular bone mineral content at the metaphysis was almost 30% lower in the PCB 118 (49mug/kg body wt/day) group compared to the control group (corn oil) (ANCOVA, P<0.05). In female foetuses of the PCB 153 (98mug/kg body wt/day) group trabecular cross-sectional area at the metaphysis was 19% smaller than in the controls (ANCOVA, P<0.05). At the diaphysis a smaller marrow cavity area (up to 24% reduction) was observed in female and male foetuses exposed to PCB 153 compared with controls (ANCOVA, P<0.05). There were also significant differences at the mid diaphyseal measure point between the PCB 153 and the control group females (ANCOVA, P<0.05). Cortical and total bone mineral density, cortical thickness were significantly higher, endosteal circumference shorter and marrow cavity significantly smaller in the PCB 153 group (ANCOVA, P<0.05). In conclusion there were gender dependent effects on bone tissue and cortical bone was more affected than trabecular bone.

  • 328.
    Gyllenhammar, Irina
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Endocrine Disruption in Amphibians: Developmental Effects of Ethynylestradiol and Clotrimazole on the Reproductive System2008Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Amphibian populations are declining world-wide and one of the suggested reasons is environmental pollutants. Studies of long-term effects on the reproductive system in frogs following larval exposure to environmental pollutants are scarce. It is therefore important to develop methods to study developmental reproductive toxicity in amphibians. In this thesis the usefulness of Xenopus tropicalis (the West African clawed frog) as a model species for a test system was investigated. Effects on the reproductive system after larval exposure to the pharmaceuticals ethynylestradiol (EE2) and clotrimazole were evaluated. The susceptibility to EE2 exposure was compared between the model species and a wild species, the European common frog (Rana temporaria). Larval exposure to EE2 caused female-biased sex ratios in both examined frog species, indicating male-to-female sex-reversal. In adult Xenopus tropicalis, male frogs that were not sex-reversed had reduced fertility and decreased amount of mature spermatozoa in the seminiferous tubules. The proportion of frogs with ovaries but lacking oviducts increased with increasing EE2-concentrations. A female frog without oviducts is sterile. The development of ovaries in sex-reversed male frogs was implied to be similar to control females. The combination of a reduced number of males, due to sex-reversal, and impaired fertility could have severe effects on frog populations. Larval exposure to clotrimazole modulated aromatase activity in gonads and brain in Xenopus tropicalis. Brain aromatase activity was decreased at the time for gonadal differentiation and gonadal aromatase activity was increased at metamorphosis. The findings in this thesis indicate that reproduction in wild frogs might be impaired by estrogenic compounds in the environment. The results combined with the short generation time supports the use of Xenopus tropicalis as a model species when evaluating long term effects of endocrine disruptors on the reproductive system in amphibians.

    List of papers
    1. Persistent sex-reversal and oviducal agenesis in adult Xenopus (Silurana) tropicalis frogs following larval exposure to the environmental pollutant ethynylestradiol
    Open this publication in new window or tab >>Persistent sex-reversal and oviducal agenesis in adult Xenopus (Silurana) tropicalis frogs following larval exposure to the environmental pollutant ethynylestradiol
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    2006 (English)In: Aquatic Toxicology, ISSN 0166-445X, E-ISSN 1879-1514, Vol. 79, no 4, p. 356-365Article in journal (Refereed) Published
    Abstract [en]

    It is known that estrogen-like environmental pollutants can feminise gonadal differentiation in frogs resulting in female-biased sex-ratios at metamorphosis. The long-term effects on reproductive function in frogs following larval exposure to pollutants are less known. Amphibian test systems which allow life-cycle studies are therefore needed. The aim of the present study was to characterise long-term estrogenic effects on the reproductive system of the emerging model species Xenopus (Silurana) tropicalis following larval exposure to ethynylestradiol (EE2). EE2 is a synthetic estrogen that has been detected in sewage effluents and in surface waters. Newly hatched tadpoles (Niewkoop Faber (NF) stage 48) were exposed to the nominal EE2 concentrations 0 (control), 1, 10, and 100 nM (with analytical chemistry support) until complete metamorphosis (NF stage 66). Effects on the reproductive organs were determined in juveniles (I month after metamorphosis) and in 9-month-old frogs. Larval exposure to EE2 caused female-biased phenotypic sex-ratios in both juvenile and adult frogs, which is in agreement with previous work on other frog species. Nearly all (97%) of the 63 EE2-exposed 9-month-old frogs had ovaries. Histological evaluation of the gonads of the 9-month-old frogs showed that they were sexually mature. Among the adult frogs with ovaries there was a dose-dependent increase in the frequency of individuals lacking oviducts. Adult frogs exposed to 100 nM EE2 that had ovaries but no oviducts had lower levels of estrogen receptor alpha (ER alpha) mRNA in the brain than control animals and those exposed to 100 nM EE2 that had ovaries as well as oviducts. EE2 exposure did not cause any significant changes in ER alpha mRNA levels in the ovaries of the adult frogs. The reduced level of ER alpha mRNA in the brain of individuals with ovaries lacking oviducts suggests an organizing effect of EE2 on the central nervous system. The results show that transient early life-stage exposure to an environmental pollutant can induce effects on the reproductive organs and the central nervous system that persist into adulthood. Overall, our data suggest that X. tropicalis, which has a shorter generation time than the well-established model species Xenopus laevis, is a suitable model organism for research on developmental reproductive toxicity in anuran species.

    Keywords
    amphibia, Xenopus (Silurana) tropicalis, test system, sex differentiation, estrogen receptor, gonad, oviduct
    National Category
    Biological Sciences
    Identifiers
    urn:nbn:se:uu:diva-97445 (URN)10.1016/j.aquatox.2006.07.004 (DOI)000241090300005 ()16942807 (PubMedID)
    Available from: 2008-09-05 Created: 2008-09-05 Last updated: 2017-12-14Bibliographically approved
    2. Environmentally Relevant Concentrations of Ethynylestradiol Cause Female-Biased Sex Ratios in Xenopus tropicalis and Rana temporaria
    Open this publication in new window or tab >>Environmentally Relevant Concentrations of Ethynylestradiol Cause Female-Biased Sex Ratios in Xenopus tropicalis and Rana temporaria
    2007 (English)In: Environmental Toxicology and Chemistry, ISSN 0730-7268, E-ISSN 1552-8618, Vol. 26, no 5, p. 1005-1009Article in journal (Refereed) Published
    Abstract [en]

    The susceptibility of Xenopus (Silurana) tropicalis and Rana temporaria to ethynylestradiol (EE2), a potent estrogenic pharmaceutical and environmental pollutant, was investigated. Larval EE2 exposure caused female-biased sex ratios at concentrations as low as 0.06 nM, which is comparable to levels found in the environment. The susceptibility of the two frog species to EE2 was comparable, supporting the use of X. tropicalis as a model organism for research on developmental reproductive toxicity of estrogenic pollutants.

    Keywords
    Amphibians, Endocrine disruption, Estrogen, Gonadal differentiation, Test system
    National Category
    Biological Sciences
    Identifiers
    urn:nbn:se:uu:diva-97446 (URN)10.1897/06-464R.1 (DOI)000245749500024 ()17521149 (PubMedID)
    Available from: 2008-09-05 Created: 2008-09-05 Last updated: 2017-12-14Bibliographically approved
    3. Reproductive Toxicity in Xenopus tropicalis after Developmental Exposure to Environmental Concentrations of Ethynylestradiol
    Open this publication in new window or tab >>Reproductive Toxicity in Xenopus tropicalis after Developmental Exposure to Environmental Concentrations of Ethynylestradiol
    2009 (English)In: Aquatic Toxicology, ISSN 0166-445X, E-ISSN 1879-1514, Vol. 91, no 2, p. 171-178Article in journal (Refereed) Published
    Abstract [en]

    Reproductive disorders in wildlife and humans have been linked to developmental exposure to endocrine disrupting chemicals. In frog tadpoles, environmental concentrations of ethynylestradiol (EE2) disrupt gonadal differentiation which results in female-biased sex ratios at metamorphosis indicating sex-reversal of genotypic males. It is not known if developmental exposure to estrogens results in reduced reproductive success in amphibians. The objective of this work was to investigate if exposure to environmentally relevant concentrations of EE2 during sex differentiation impairs reproductive organ development, fertility, and sexual behavior in adult frogs. A specific aim was to evaluate if testicular structure and function was affected in males that were not sex-reversed. Xenopus tropicalis tadpoles were exposed until metamorphosis to 6, 60, and 600 pM EE2. Eight months after metamorphosis, reproductive organ morphology and fertility were evaluated. Larval EE2-exposure caused an increased proportion of phenotypic females indicating that sex-reversal of genotypic males is persistent. Sex-reversal was implied at concentrations as low as 6 pM (1.8 ng/l), which is comparable to levels observed in the environment. EE2-exposed males that were not sex-reversed had a significantly reduced fertilization rate compared with control males. Histological evaluation revealed that EE2-exposed males had a reduced amount of spermatozoa in the testis. Among frogs with ovaries there was a significantly higher percentage that lacked oviducts in the group exposed to 600 pM EE2 compared with control females. No effect of EE2 on sexual behavior was noted. The results indicate that reproduction in wild frogs might be impaired by estrogenic environmental pollutants. Similarities between the present effects and those reported in fish, birds and mammals after developmental exposure to estrogens suggest that X. tropicalis is a promising animal model for research on developmental reproductive toxicity.

    Keywords
    Amphibians, Endocrine disruption, Estrogen, Sex differentiation, Testicular histology, Sperm quality
    National Category
    Biological Sciences
    Identifiers
    urn:nbn:se:uu:diva-87137 (URN)10.1016/j.aquatox.2008.06.019 (DOI)000263452500010 ()18692912 (PubMedID)
    Available from: 2008-09-15 Created: 2008-09-15 Last updated: 2017-12-14Bibliographically approved
    4. Xenopus tropicalis as a Test System for Developmental and Reproductive Toxicity
    Open this publication in new window or tab >>Xenopus tropicalis as a Test System for Developmental and Reproductive Toxicity
    2009 (English)In: Journal of Toxicology and Environmental Health, ISSN 1528-7394, E-ISSN 1087-2620, Vol. 72, no 3-4, p. 219-225Article in journal (Refereed) Published
    Abstract [en]

    The usefulness of Xenopus tropicalis as a model species to investigate endocrine disruption and developmental reproductive toxicity was assessed. In our test system tadpoles were exposed to test substances from shortly after hatching until metamorphosis, including the period of gonadal differentiation. Effects on the sex hormone and thyroid hormone axes were evidenced as skewed sex ratios, malformations of reproductive organs, altered cytochrome (CYP19) (aromatase) activity, and gene expression in gonads and brain, as well as changed thyroid histology and time to metamorphosis. Reproductive toxicity was evaluated at sexual maturity. Male-to-female sex reversal was implied at concentrations as low as 6 pM (1.8 ng/L) ethynylestradiol (EE2), which is comparable to EE2 levels observed in the environment. EE2-exposed males that were not sex reversed had significantly reduced fertility and a reduced amount of spermatozoa in testes compared with control males. This indicates that reproduction in wild frogs might be impaired by estrogenic environmental pollutants. Aromatase activity in brain and testes of adult frogs was not affected by larval EE2 exposure. Preliminary results indicate that exposure to the environmentally relevant pharmaceutical clotrimazole modulated aromatase activity in brain and gonads during sex differentiation, which warrants further investigation. The susceptibility to estrogen-induced sex reversal of X. tropicalis was comparable to that of other frog species and fish. Similarities between the reproductive effects in X. tropicalis and those reported in fish, birds, and mammals after developmental exposure to estrogens make X. tropicalis promising model for research on endocrine disruption and developmental reproductive toxicity.

    National Category
    Pharmacology and Toxicology
    Identifiers
    urn:nbn:se:uu:diva-87138 (URN)10.1080/15287390802539079 (DOI)000263013000011 ()
    Available from: 2008-09-15 Created: 2008-09-15 Last updated: 2018-01-13Bibliographically approved
    5. Clotrimazole exposure modulates aromatase activity in gonads and brain during gonadal differentiation in Xenopus tropicalis frogs
    Open this publication in new window or tab >>Clotrimazole exposure modulates aromatase activity in gonads and brain during gonadal differentiation in Xenopus tropicalis frogs
    Show others...
    2009 (English)In: Aquatic Toxicology, ISSN 0166-445X, E-ISSN 1879-1514, Vol. 91, no 2, p. 102-109Article in journal (Refereed) Published
    Abstract [en]

    Clotrimazole is a pharmaceutical used for treatment of fungal infections. It has been found in surface waters outside municipal wastewater treatment plants but data are scarce regarding its effects on aquatic organisms. It is known that clotrimazole and other imidazole fungicides are inhibitors of the enzyme aromatase (CYP 19). Aromatase converts androgens into estrogens and is suggested to be involved in the sex differentiation in amphibians. The aim of the present study was to evaluate effects of larval exposure to clotrimazole on aromatase activity in brain and gonads, and on gonadal differentiation in Xenopus tropicalis frogs. Another purpose was to determine if larval exposure to ethynylestradiol (EE(2)), at a concentration known to cause male-to-female sex reversal, affects aromatase activity in brain and gonads during gonadal differentiation. Tadpoles were exposed from shortly after hatching (Nieuwkoop and Faber developmental stages 47-48) until complete metamorphosis (NF stage 66) to 6, 41, and 375 nM clotrimazole or 100 nM (nominal) EE(2). Aromatase activity was measured in the brain and gonad/kidney complex of tadpoles during gonadal differentiation (NF stage 56) and, in the clotrimazole experiment, also at metamorphosis. In clotrimazole-exposed tadpoles gonadal aromatase activity increased over exposure time in the 41 and 375 nM groups but did not differ significantly from the control group. Gonadal aromatase activity was increased in both sexes exposed to 41 and 375 nM clotrimazole at metamorphosis. Brain aromatase activity was decreased in tadpoles (NF stage 56) exposed to 375 nM clotrimazole, but at metamorphosis no differences were seen between groups or between sexes. No effects of clotrimazole on sex ratio or gonadal histology were noted at completed metamorphosis. EE(2)-exposed tadpoles had a slightly decreased gonadal aromatase activity, though not significantly different from control group, and there was no effect of EE(2) on brain aromatase activity. All EE(2)-exposed tadpoles developed ovaries. These findings indicate that estrogen-induced ovarian differentiation is not paralleled by increased gonadal aromatase activity in X. tropicalis. Further studies are needed, especially on developmental reproductive toxicity, to assess the risk for endocrine disruption in wild amphibians posed by clotrimazole and other imidazole fungicides.

    Keywords
    Amphibians, Imidazole, Estrogen, Cytochrome p450, Sex differentiation, Endocrine disruption, Steroidogenesis
    National Category
    Biological Sciences
    Identifiers
    urn:nbn:se:uu:diva-97449 (URN)10.1016/j.aquatox.2008.10.005 (DOI)000263452500002 ()19036460 (PubMedID)
    Available from: 2008-09-05 Created: 2008-09-05 Last updated: 2017-12-14Bibliographically approved
    Download full text (pdf)
    FULLTEXT01
  • 329.
    Gyllenhammar, Irina
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Eriksson, Hanna
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Söderqvist, Anneli
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Lindberg, Richard
    Department of Chemistry, Umeå University.
    Fick, Jerker
    Department of Chemistry, Umeå University.
    Berg, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Clotrimazole exposure modulates aromatase activity in gonads and brain during gonadal differentiation in Xenopus tropicalis frogs2009In: Aquatic Toxicology, ISSN 0166-445X, E-ISSN 1879-1514, Vol. 91, no 2, p. 102-109Article in journal (Refereed)
    Abstract [en]

    Clotrimazole is a pharmaceutical used for treatment of fungal infections. It has been found in surface waters outside municipal wastewater treatment plants but data are scarce regarding its effects on aquatic organisms. It is known that clotrimazole and other imidazole fungicides are inhibitors of the enzyme aromatase (CYP 19). Aromatase converts androgens into estrogens and is suggested to be involved in the sex differentiation in amphibians. The aim of the present study was to evaluate effects of larval exposure to clotrimazole on aromatase activity in brain and gonads, and on gonadal differentiation in Xenopus tropicalis frogs. Another purpose was to determine if larval exposure to ethynylestradiol (EE(2)), at a concentration known to cause male-to-female sex reversal, affects aromatase activity in brain and gonads during gonadal differentiation. Tadpoles were exposed from shortly after hatching (Nieuwkoop and Faber developmental stages 47-48) until complete metamorphosis (NF stage 66) to 6, 41, and 375 nM clotrimazole or 100 nM (nominal) EE(2). Aromatase activity was measured in the brain and gonad/kidney complex of tadpoles during gonadal differentiation (NF stage 56) and, in the clotrimazole experiment, also at metamorphosis. In clotrimazole-exposed tadpoles gonadal aromatase activity increased over exposure time in the 41 and 375 nM groups but did not differ significantly from the control group. Gonadal aromatase activity was increased in both sexes exposed to 41 and 375 nM clotrimazole at metamorphosis. Brain aromatase activity was decreased in tadpoles (NF stage 56) exposed to 375 nM clotrimazole, but at metamorphosis no differences were seen between groups or between sexes. No effects of clotrimazole on sex ratio or gonadal histology were noted at completed metamorphosis. EE(2)-exposed tadpoles had a slightly decreased gonadal aromatase activity, though not significantly different from control group, and there was no effect of EE(2) on brain aromatase activity. All EE(2)-exposed tadpoles developed ovaries. These findings indicate that estrogen-induced ovarian differentiation is not paralleled by increased gonadal aromatase activity in X. tropicalis. Further studies are needed, especially on developmental reproductive toxicity, to assess the risk for endocrine disruption in wild amphibians posed by clotrimazole and other imidazole fungicides.

  • 330.
    Gyllenhammar, Irina
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Holm, Lena
    Institutionen för anatomi och fysiologi, SLU.
    Eklund, Rosita
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Berg, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Reproductive Toxicity in Xenopus tropicalis after Developmental Exposure to Environmental Concentrations of Ethynylestradiol2009In: Aquatic Toxicology, ISSN 0166-445X, E-ISSN 1879-1514, Vol. 91, no 2, p. 171-178Article in journal (Refereed)
    Abstract [en]

    Reproductive disorders in wildlife and humans have been linked to developmental exposure to endocrine disrupting chemicals. In frog tadpoles, environmental concentrations of ethynylestradiol (EE2) disrupt gonadal differentiation which results in female-biased sex ratios at metamorphosis indicating sex-reversal of genotypic males. It is not known if developmental exposure to estrogens results in reduced reproductive success in amphibians. The objective of this work was to investigate if exposure to environmentally relevant concentrations of EE2 during sex differentiation impairs reproductive organ development, fertility, and sexual behavior in adult frogs. A specific aim was to evaluate if testicular structure and function was affected in males that were not sex-reversed. Xenopus tropicalis tadpoles were exposed until metamorphosis to 6, 60, and 600 pM EE2. Eight months after metamorphosis, reproductive organ morphology and fertility were evaluated. Larval EE2-exposure caused an increased proportion of phenotypic females indicating that sex-reversal of genotypic males is persistent. Sex-reversal was implied at concentrations as low as 6 pM (1.8 ng/l), which is comparable to levels observed in the environment. EE2-exposed males that were not sex-reversed had a significantly reduced fertilization rate compared with control males. Histological evaluation revealed that EE2-exposed males had a reduced amount of spermatozoa in the testis. Among frogs with ovaries there was a significantly higher percentage that lacked oviducts in the group exposed to 600 pM EE2 compared with control females. No effect of EE2 on sexual behavior was noted. The results indicate that reproduction in wild frogs might be impaired by estrogenic environmental pollutants. Similarities between the present effects and those reported in fish, birds and mammals after developmental exposure to estrogens suggest that X. tropicalis is a promising animal model for research on developmental reproductive toxicity.

  • 331.
    Göndör, Anita
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Animal Development and Genetics.
    Epigenetic Regulation of Higher Order Chromatin Conformations and Gene Transcription2007Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Epigenetic states constitute heritable features of the chromatin to regulate when, where and how genes are expressed in the developing conceptus. A special case of epigenetic regulation, genomic imprinting, is defined as parent of origin-dependent monoallelic expression. The Igf2-H19 locus is considered as paradigm of genomic imprinting with a growth-promoting gene, Igf2, expressed paternally and a growth antagonist, H19 encoding a non-coding transcript, expressed only from the maternal allele. The monoallelic expression patterns are regulated by the epigenetic status at an imprinting control region (ICR) in the 5´-flank of the H19 gene. The chromatin insulator protein CTCF interacts with only the maternal H19 ICR allele to prevent downstream enhancers to communicate with the Igf2 promoters. Mutations of these CTCF binding sites lead to biallelic Igf2 expression, increased size of the conceptus and predisposition for cancer.

    Reasoning that these effects cannot be explained by the regulation of Igf2 expression alone, a technique was invented to examine long-range chromatin interactions without prior knowledge of the interacting partners. Applying the circular chromosomal conformation capture (4C) technique to mouse neonatal liver cells, it was observed that 114 unique sequences interacted with the H19 ICR. A majority of these interactors was in complex with only the maternal H19 ICR allele and depended on the presence of functional CTCF binding sites. The functional consequence of chromosomal networks was demonstrated by the observation that the maternal H19 ICR allele regulated the transcription of two genes on another chromosome. As the chromosomal networks underwent reprogramming during the maturation of embryonic stem cells, attention was turned to human cancer cells, displaying features common with mouse embryonic stem cells. Subsequently, chromatin folding at the human H19 ICR suggested that stable chromatin loops were organized by synergistic interactions within and between baits and interactors. The presence of these interactions was linked to DNA methylation patterns involving repeat elements. A "flower" model of chromatin networks was formulated to explain these observations.

    This thesis has unravealed a novel feature of the epigenome and its functions to regulate gene expression in trans. The identified roles for CTCF as an architectural factor in the organization of higher order chromatin conformations may be of importance in understanding development and disease ontogeny from novel perspectives.

    List of papers
    1. Circular chromosome conformation capture (4C) uncovers extensive networks of epigenetically regulated intra- and interchromosomal interactions
    Open this publication in new window or tab >>Circular chromosome conformation capture (4C) uncovers extensive networks of epigenetically regulated intra- and interchromosomal interactions
    Show others...
    2006 (English)In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 38, no 11, p. 1341-1347Article in journal (Refereed) Published
    Abstract [en]

    Accumulating evidence converges on the possibility that chromosomes interact with each other to regulate transcription in trans. To systematically explore the epigenetic dimension of such interactions, we devised a strategy termed circular chromosome conformation capture (4C). This approach involves a circularization step that enables high-throughput screening of physical interactions between chromosomes without a preconceived idea of the interacting partners. Here we identify 114 unique sequences from all autosomes, several of which interact primarily with the maternally inherited H19 imprinting control region. Imprinted domains were strongly overrepresented in the library of 4C sequences, further highlighting the epigenetic nature of these interactions. Moreover, we found that the direct interaction between differentially methylated regions was linked to epigenetic regulation of transcription in trans. Finally, the patterns of interactions specific to the maternal H19 imprinting control region underwent reprogramming during in vitro maturation of embryonic stem cells. These observations shed new light on development, cancer epigenetics and the evolution of imprinting.

    National Category
    Biological Sciences
    Identifiers
    urn:nbn:se:uu:diva-96389 (URN)10.1038/ng1891 (DOI)000241592700025 ()17033624 (PubMedID)
    Available from: 2007-10-31 Created: 2007-10-31 Last updated: 2017-12-14Bibliographically approved
    2. A high-resolution map of chromatin loops impinging on the human H19 imprinting control region in cis uncovers a re-peat element-based higher order chromatin structure
    Open this publication in new window or tab >>A high-resolution map of chromatin loops impinging on the human H19 imprinting control region in cis uncovers a re-peat element-based higher order chromatin structure
    Show others...
    (English)Manuscript (Other (popular science, discussion, etc.))
    Identifiers
    urn:nbn:se:uu:diva-96390 (URN)
    Available from: 2007-10-31 Created: 2007-10-31 Last updated: 2010-01-14Bibliographically approved
    3. High-resolution circular chromosomal conformation cap-ture (4C) assay
    Open this publication in new window or tab >>High-resolution circular chromosomal conformation cap-ture (4C) assay
    (English)Manuscript (Other (popular science, discussion, etc.))
    Identifiers
    urn:nbn:se:uu:diva-96391 (URN)
    Available from: 2007-10-31 Created: 2007-10-31 Last updated: 2010-01-14Bibliographically approved
    4. The 4C technique: the ‘Rosetta stone’ for genome biology in 3D?
    Open this publication in new window or tab >>The 4C technique: the ‘Rosetta stone’ for genome biology in 3D?
    2007 (English)In: Current Opinion in Cell Biology, ISSN 0955-0674, E-ISSN 1879-0410, Vol. 19, no 3, p. 321-325Article in journal (Refereed) Published
    Abstract [en]

    Despite considerable efforts, the spatial link between the nuclear architecture and the genome remains enigmatic. The 4C method, independently innovated in four different laboratories, might in combination with other methods change that. As this method is based on the unbiased identification of sequences interacting with specific baits, there are unique opportunities for unravelling the secrets of how the genome functions in 3D.

    National Category
    Biological Sciences
    Identifiers
    urn:nbn:se:uu:diva-96392 (URN)10.1016/j.ceb.2007.04.008 (DOI)000247775200012 ()
    Available from: 2007-10-31 Created: 2007-10-31 Last updated: 2017-12-14Bibliographically approved
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  • 332.
    Göndör, Anita
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology.
    Ohlsson, Rolf
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology.
    Chromatin insulators and cohesins2008In: EMBO Reports, ISSN 1469-221X, E-ISSN 1469-3178, Vol. 9, no 4, p. 327-329Article in journal (Refereed)
  • 333.
    Göndör, Anita
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Animal Development and Genetics. zoologisk utvecklingsbiologi.
    Ohlsson, Rolf
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Animal Development and Genetics. zoologisk utvecklingsbiologi.
    Transcription in the loop.2006In: Nat Genet, ISSN 1061-4036, Vol. 38, no 11, p. 1229-30Article in journal (Refereed)
  • 334.
    Göndör, Anita
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Animal Development and Genetics.
    Rougier, Carole
    Ohlsson, Rolf
    High-resolution circular chromosomal conformation cap-ture (4C) assayManuscript (Other (popular science, discussion, etc.))
  • 335.
    Göndör, Anita
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology.
    Rougier, Carole
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology.
    Ohlsson, Rolf
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology.
    High-resolution circular chromosome conformation capture assay2008In: Nature protocols, ISSN 1754-2189, Vol. 3, no 2, p. 303-313Article in journal (Refereed)
    Abstract [en]

    The pioneering chromosome conformation capture (3C) method provides the opportunity to study chromosomal folding in the nucleus. It is based on formaldehyde cross-linking of living cells followed by enzyme digestion, intramolecular ligation and quantitative (Q)-PCR analysis. However, 3C requires prior knowledge of the bait and interacting sequence (termed interactor) rendering it less useful for genome-wide studies. As several recent reports document, this limitation has been overcome by exploiting a circular intermediate in a variant of the 3C method, termed 4C (for circular 3C). The strategic positioning of primers within the bait enables the identification of unknown interacting sequences, which form part of the circular DNA. Here, we describe a protocol for our 4C method, which produces a high-resolution interaction map potentially suitable for the analysis of cis-regulatory elements and for comparison with chromatin marks obtained by chromatin immunoprecipitation (ChIP) on chip at the sites of interaction. Following optimization of enzyme digestions and amplification conditions, the protocol can be completed in 2-3 weeks.

  • 336.
    Göndör, Anita
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Animal Development and Genetics.
    Rougier, Carole
    Singh Sandhu, Kuljeet
    Sumida, Noriyuki
    Holodnuk, Irina
    Wang, Sha
    Ohlsson, Rolf
    A high-resolution map of chromatin loops impinging on the human H19 imprinting control region in cis uncovers a re-peat element-based higher order chromatin structureManuscript (Other (popular science, discussion, etc.))
  • 337. Haaf, Thomas
    et al.
    Shi, Wei
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Animal Development and Genetics.
    Fundele, Reinald
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Animal Development and Genetics.
    Arney, Katharine L.
    Surani, M. Azim
    Barton, Sheila C.
    Differential dementhylation of paternal and maternal genomes in the preimplantation mouse embryo: implications for mammalian development2004In: Chromosomes today / [ed] Schmid, Michael, Nanda, Indrajit, Dordrecht: Kluwer , 2004, Vol. 14, p. 207-214Chapter in book (Other academic)
  • 338. Hadzhiev, Yavor
    et al.
    Lele, Zsolt
    Schindler, Simon
    Wilson, Stephen W.
    Ahlberg, Per
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Evolutionary Organism Biology.
    Strähle, Uwe
    Müller, Ferenc
    Hedgehog signaling patterns the outgrowth of unpaired skeletal appendages in zebrafish2007In: BMC Developmental Biology, ISSN 1471-213X, E-ISSN 1471-213X, Vol. 7, p. 75-Article in journal (Refereed)
    Abstract [en]

    Background

    Little is known about the control of the development of vertebrate unpaired appendages such as the caudal fin, one of the key morphological specializations of fishes. Recent analysis of lamprey and dogshark median fins suggests the co-option of some molecular mechanisms between paired and median in Chondrichthyes. However, the extent to which the molecular mechanisms patterning paired and median fins are shared remains unknown.

    Results

    Here we provide molecular description of the initial ontogeny of the median fins in zebrafish and present several independent lines of evidence that Sonic hedgehog signaling emanating from the embryonic midline is essential for establishment and outgrowth of the caudal fin primordium. However, gene expression analysis shows that the primordium of the adult caudal fin does not harbor a Sonic hedgehog-expressing domain equivalent to the Shh secreting zone of polarizing activity (ZPA) of paired appendages.

    Conclusion

    Our results suggest that Hedgehog proteins can regulate skeletal appendage outgrowth independent of a ZPA and demonstrates an unexpected mechanism for mediating Shh signals in a median fin primordium. The median fins evolved before paired fins in early craniates, thus the patterning of the median fins may be an ancestral mechanism that controls the outgrowth of skeletogenic appendages in vertebrates.

  • 339. Hairapetian, Vachik
    et al.
    Blom, Henning
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Evolutionary Organism Biology.
    Miller, C. Giles
    Silurian thelodonts from the Niur Formation, central Iran2008In: Acta Palaeontologica Polonica, ISSN 0567-7920, E-ISSN 1732-2421, Vol. 53, no 1, p. 85-95Article in journal (Refereed)
    Abstract [en]

    Thelodont scales are described from the Silurian Niur Formation in the Derenjal Mountains, east central Iran. The material studied herein comes from four stratigraphic levels, composed of rocks formed in a shallow water, carbonate ramp environment. The fauna includes a new phlebolepidiform, Niurolepis susanae gen. et sp. nov. of late Wenlock/?early Ludlow age and a late Ludlow loganelliiform, Loganellia sp. cf. L. grossi, which constitute the first record of these thelodont groups from Gondwana. The phlebolepidiform Niurolepis susanae gen. et sp. nov. is diagnosed by having trident trunk scales with a raised medial crown area separated by two narrow spiny wings from the lateral crown areas; a katoporodid-type histological structure distinguished by a network of branched wide dentine canals. Other scales with a notch on a smooth rhomboidal crown and postero-laterally down-stepped lateral rims have many characters in common with Loganellia grossi. Associated with the thelodonts are indeterminable acanthodian scales and a possible dentigerous jaw bone fragment. This finding also provides evidence of a hitherto unknown southward dispersal of Loganellia to the shelves of peri-Gondwana.

  • 340.
    Hairapetian, Vachik
    et al.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Evolutionary Organism Biology.
    Blom, Henning
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Evolutionary Organism Biology. Evolutionär organismbiologi.
    Miller, Giles
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Evolutionary Organism Biology.
    Silurian thelodonts from the Niur Formation, east central Iran. Early vertebrates2007In: 40th Anniversary Symposium on Early Vertebrates/Lower Vertebrates Uppsala, Sweden, August 13-16, 2007, 2007, p. 43-44Conference paper (Other scientific)
  • 341. Hall, M
    et al.
    Scott, T
    Sugumaran, M
    Söderhäll, K
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Comparative Physiology. jämförande fysiologi.
    Law, J H
    Proenzyme of Manduca sexta phenol oxidase: purification, activation, substrate specificity of the active enzyme, and molecular cloning.1995In: Proc Natl Acad Sci U S A, ISSN 0027-8424, Vol. 92, no 17, p. 7764-8Article in journal (Refereed)
  • 342. Hall, M
    et al.
    van Heusden, M C
    Söderhäll, K
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Comparative Physiology.
    Identification of the major lipoproteins in crayfish hemolymph as proteins involved in immune recognition and clotting.1995In: Biochem Biophys Res Commun, ISSN 0006-291X, Vol. 216, no 3, p. 939-46Article in journal (Refereed)
  • 343. HALL, M
    et al.
    VANHEUSDEN, MC
    SODERHALL, K
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Comparative Physiology. Jämförande fysiologi.
    IDENTIFICATION OF THE MAJOR LIPOPROTEINS IN CRAYFISH HEMOLYMPH AS PROTEINS INVOLVED IN IMMUNE RECOGNITION AND CLOTTING1995In: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, ISSN 0006-291X, Vol. 216, no 3, p. 939-946Article in journal (Refereed)
  • 344. Hall, M
    et al.
    Wang, RG
    van, Antwerpen R
    Sottrup-Jensen, L
    Söderhäll, K
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Comparative Physiology. jämförande fysiologi.
    The crayfish plasma clotting protein: A vitellogenin-related protein responsible for clot formation in crustacean blood1999In: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, ISSN 0027-8424, Vol. 96, no 5, p. 1965-1970Article in journal (Refereed)
    Abstract [en]

    Coagulation in crayfish blood is based on the transglutaminase-mediated crosslinking of a specific plasma clotting protein. Here we report the cloning of the subunit of this clotting protein from a crayfish hepatopancreas cDNA library. The ORF encodes a p

  • 345. Halldin, K
    et al.
    Berg, C
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Brandt, I
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Brunstrom, B
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Sexual behavior in Japanese quail as a test end point for endocrine disruption: Effects of in Ovo exposure to ethinylestradiol and diethylstilbestrol1999In: ENVIRONMENTAL HEALTH PERSPECTIVES, ISSN 0091-6765, Vol. 107, no 11, p. 861-866Article in journal (Other scientific)
    Abstract [en]

    Chemicals having a capacity to disturb the endocrine system have attracted considerable interest during recent years. There is a shortage of well-characterized in vivo tests with which to study such disturbances in different classes of vertebrates. In the

  • 346.
    Halldin, Krister
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Embryonic co-exposure to methoxychlor and Clophen A50 alters sexual behavior in adult male quail2005In: Archives of Toxicology, Vol. 79, no 4, p. 237-42Article in journal (Refereed)
  • 347. Halldin, Krister
    et al.
    Axelsson, Jeanette
    Avd för ekotoxikologi. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Brandt, Ingvar
    Avd för ekotoxikologi. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Brunström, Björn
    Avd för ekotoxikologi. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Developmental toxicity in Japanese quail exposed to hydroxylated metabolites pf PCBs in ovo.2005In: Avian and Poultry Biology Reviews, no 16, p. 11-17Article in journal (Refereed)
  • 348. Halldin, Krister
    et al.
    Axelsson, Jeanette
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Brunström, Björn
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Effects of endocrine modulators on sexual differentiation and reproductive function in male Japanese quail.2005In: Brain Res Bull, ISSN 0361-9230, Vol. 65, no 3, p. 211-8Article in journal (Refereed)
  • 349. Halldin, Krister
    et al.
    Axelsson, Jeanette
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Brunström, Björn
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Embryonic co-exposure to methoxychlor and Clophen A50 alters sexual behavior in adult male quail.2005In: Arch Toxicol, ISSN 0340-5761, Vol. 79, no 4, p. 237-42Article in journal (Refereed)
  • 350. Halldin, Krister
    et al.
    Axelsson, Jeanette
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Brunström, Björn
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Environmental Toxicology.
    Localization of Estrogen Receptor -alpha and -beta mRNA in the Brain of Embryonic and Adult Japanese Quail2003In: Trabajos del Instituto Cajal, 2003, p. 279-Conference paper (Other academic)
45678910 301 - 350 of 807
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