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  • 1.
    Ahlberg, Per E.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Evolutionary Organism Biology.
    Blom, Henning
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Evolutionary Organism Biology.
    Brazeau, Martin
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Evolutionary Organism Biology.
    Clément, Gaël
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Evolutionary Organism Biology.
    Snitting, Daniel
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Evolutionary Organism Biology.
    The virtual Eusthenopteron: inside the head of a Devonian lobe-fin with CT. In A. Ivanov and G. Young (eds.), Middle Palaeozoic Vertebrates from Laurussia: Relationships with Siberia, Kazakhstan, Asia and Gondwana. Ichthyolith Issues Special Publication 9:3–4.2005Other (Other academic)
  • 2.
    Ahlberg, Per E.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Evolutionary Organism Biology.
    Clack, Jennifer A.
    Palaeontology: A firm step from water to land2006In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 440, no 7085, p. 747-749Article in journal (Refereed)
  • 3.
    Ahlberg, Per Erik
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Evolution and Developmental Biology.
    Humeral homology and the origin of the tetrapod elbow: a reinterpretation of the enigmatic specimens ANSP 21350 and GSM 1045362011In: Studies on fossil tetrapods / [ed] P. M. Barrett, A. R. Milner, London: The Palaeontological Association , 2011, p. 17-29Chapter in book (Refereed)
    Abstract [en]

    Two putative tetrapod humeri of Devonian age, ANSP 21350 from the late Famennian of Pennsylvania and GSM 104536 from the late Frasnian of Scat Craig, Scotland, are reinterpreted in the light of more recent discoveries. The morphology of ANSP 21350 can be more fully homologized with those of elpistostegids and early tetrapods than previously recognized. Unique features include distally displaced dorsal muscle attachments and a ventrally rotated distal face of the bone. This suggests that a weight-bearing ventrally directed forearm was created, not by means of a flexed elbow as in other tetrapods, but by distorting the humerus. The olecranon process on the ulna was probably poorly developed or absent. Primitive characters that are absent in other tetrapods add support to the contention that ANSP 21350 is the least crownward of known tetrapod humeri. Contrary to previous claims, Acanthostega has a characteristic tetrapod ulnar morphology with an olecranon process; it does not resemble an elpistostegid ulna and is not uniquely primitive for tetrapods. This suggests that the flexed tetrapod elbow with ulnar extensor muscles attached to the olecranon evolved simultaneously with the large rectangular entepicondyle typical for early tetrapods, probably as part of a single functional complex. GSM 104536 is denfinitely not a primitive tetrapod humerus, nor a sarcopterygian branchial bone, but cannot be positively identified at present.    

  • 4.
    Alsmark, Cecilia
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Evolutionary Biology, Molecular Evolution.
    Comparative Genomics of Obligate and Facultative Intracellular Parasites2002Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The α-proteobacteria Rickettsia prowazekii and Bartonella henselae are the causative agents of epidemic typhus and cat scratch disease respectively. Whereas R. prowazekii is an obligate intracellular parasite, B. henselae can live and proliferate both outside and inside the eukaryotic host cell. Besides the obvious medical interest to identify the complete gene set of two human pathogens, their genome sequences are also important for the study of evolutionary processes. Both R. prowazekii and B. henselae have small genomes, but their last common ancestor of these two bacteria was most likely a free-living organism with a substantially larger genome.

    The aim of this thesis is to compare the complete genomes of R. prowazekii and B. henselae and to decipher the evolutionary processes leading to the adaptation to an intracellular lifestyle. The working hypothesis was that the facultative intracellular B. henselae is an intermediate between a free living bacteria and the obligate R. prowazekii, which is corroborated. B. henselae has a broader biosynthetic repertoire than R. prowazekii, including the presence of genes for glycolysis and de novo biosynthesis of purines and pyrimidines. However, both bacteria have reduced gene sets for biosynthesis of amino acids and cofactors compared to free-living bacteria.

    Comparisons of gene order in bacteria reveal that several operons are well conserved between distantly related species. The genome sequences of R. prowazekii and B. henselae show that many of the operons that are usually conserved, are broken and rearranged in these species. One of the mechanisms of reductive evolution include intra-chromosomal recombination between repeated loci. This process expels one of the repeats and cause rearrangements in the gene order of the flanking regions. While the R. prowazekii genome almost completely lack repeated sequences, the B. henselae genome is rich in repeats. These repeats are, however, most often located within regions associated with pathogenicity islands. The higher number of scrambled operons, and the lower number of repeats, in R. prowazekii compared to B. henselae imply that the reductive process has gone further in the former species.

  • 5.
    Amiri, Haleh
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Evolutionary Biology, Molecular Evolution.
    Patterns and Processes of Molecular Evolution in Rickettsia2002Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Species of the genus Rickettsia are obligate intracellular parasites of the a-proteobacterial subdivision. It has been suggested that obligate intracellular bacteria have evolved from free-living bacteria with much larger genome sizes. Transitions to intracellular growth habitats are normally associated with radical genomic alterations, particularly genome rearrangements and gene losses.

    This thesis presents a comparative study of evolutionary processes such as gene rearrangements, deletions and duplications in a variety of Rickettsia species. The results show that early intrachromosomal recombination events mediated by duplicated genes and short repeats have resulted in deletions as well as rearrangements. For example, an exceptional organization of the elongation factor genes was found in all species examined, suggesting that this rearrangement event occurred at the early stage of the evolution of Rickettsia. Likewise, it was found that a repetitive element, the so-called Rickettsia Palindromic Element (RPE) flourished prior to species divergence in Rickettsia. Finally, a phylogenetic analysis shows that the duplication events that gave rise to the five genes encoding ATP/ADP transporters occurred long before the divergence of the two major groups of Rickettsia. Taken together, this suggests that Rickettsia have been intracellular parasites for an extensive period of time.

    A detailed analysis of the patterns of nucleotide changes in genes and intergenic regions among the different species provides evidence for a gradual accumulation of short deletions. This suggests that different distributions of genes and repeated sequences in modern Rickettsia species reflect species-specific differences in rates of deterioration rather than variation in rates of intra-genomic sequence proliferation.

    List of papers
    1. A chimeric disposition of the elongation factor genes in Rickettsia prowazekii
    Open this publication in new window or tab >>A chimeric disposition of the elongation factor genes in Rickettsia prowazekii
    Show others...
    1996 In: J. Bacteriol., Vol. 178, p. 6192-6199Article in journal (Refereed) Published
    Identifiers
    urn:nbn:se:uu:diva-89688 (URN)
    Available from: 2002-03-06 Created: 2002-03-06Bibliographically approved
    2. Proliferation and deterioration of Rickettsia palindromic elements
    Open this publication in new window or tab >>Proliferation and deterioration of Rickettsia palindromic elements
    2002 (English)In: Molecular biology and evolution, ISSN 0737-4038, E-ISSN 1537-1719, Vol. 19, no 8, p. 1234-1243Article in journal (Refereed) Published
    Abstract [en]

    It has been suggested that Rickettsia Palindromic Elements (RPEs) have evolved as selfish DNA that mediate protein sequence evolution by being targeted to genes that code for RNA and proteins. Here, we have examined the phylogenetic depth of two RPEs that are located close to the genes encoding elongation factors Tu (tuf) and G (fus) in Rickettsia. An exceptional organization of the elongation factor genes was found in all 11 species examined, with complete or partial RPEs identified downstream of the tuf gene (RPE-tuf) in six species and of the fus gene (RPE-fus) in 10 species. A phylogenetic reconstruction shows that both RPE-tuf and RPE-fus have evolved in a manner that is consistent with the expected species divergence. The analysis provides evidence for independent loss of RPE-tuf in several species, possibly mediated by short repetitive sequences flanking the site of excision. The remaining RPE-tuf sequences evolve as neutral sequences in different stages of deterioration. Likewise, highly fragmented remnants of the RPE-fus sequence were identified in two species. This suggests that genome-specific differences in the content of RPEs are the result of recent loss rather than recent proliferation.

    National Category
    Biochemistry and Molecular Biology
    Identifiers
    urn:nbn:se:uu:diva-89689 (URN)12140235 (PubMedID)
    Available from: 2002-03-06 Created: 2002-03-06 Last updated: 2017-12-14Bibliographically approved
    3. In the phylogenetic footsteps of ATP- ADP translocases
    Open this publication in new window or tab >>In the phylogenetic footsteps of ATP- ADP translocases
    Manuscript (Other academic)
    Identifiers
    urn:nbn:se:uu:diva-89690 (URN)
    Available from: 2002-03-06 Created: 2002-03-06 Last updated: 2010-01-13Bibliographically approved
    4. Evolution of intergenic DNA in Rickettsia
    Open this publication in new window or tab >>Evolution of intergenic DNA in Rickettsia
    Manuscript (Other academic)
    Identifiers
    urn:nbn:se:uu:diva-89691 (URN)
    Available from: 2002-03-06 Created: 2002-03-06 Last updated: 2010-01-13Bibliographically approved
    5. Loss of gene function: Clues from expressed gene fragments in Rickettsia
    Open this publication in new window or tab >>Loss of gene function: Clues from expressed gene fragments in Rickettsia
    2002 (English)In: Trends in Genetics, ISSN 0168-9525, E-ISSN 1362-4555, Vol. 18, no 7, p. 331-334Article in journal (Refereed) Published
    Abstract [en]

    Many obligate intracellular pathogens have small genomes with high fractions of pseudogenes. A recent analysis of gene expression patterns in Rickettsia conorii shows that short open reading frames inside deteriorating genes are occasionally transcribed into RNA. Here, we show that substitution frequencies at nonsynonymous sites are similar for expressed and unexpressed parts of the fragmented genes. We conclude that the observed expression is a temporary stage in the gene degradation process, suggesting that the expressed gene fragments are not functional.

    National Category
    Natural Sciences
    Identifiers
    urn:nbn:se:uu:diva-89692 (URN)10.1016/S0168-9525(02)02685-9 (DOI)
    Available from: 2002-03-06 Created: 2002-03-06 Last updated: 2017-12-14Bibliographically approved
    6. Genome deterioration: Loss of repeated sequences and accumulation of junk DNA
    Open this publication in new window or tab >>Genome deterioration: Loss of repeated sequences and accumulation of junk DNA
    2002 (English)In: Genetica, ISSN 0016-6707, E-ISSN 1573-6857, Vol. 115, no 1, p. 1-12Article in journal (Refereed) Published
    Abstract [en]

    A global survey of microbial genomes reveals a correlation between genome size, repeat content and lifestyle. Free-living bacteria have large genomes with a high content of repeated sequences and self-propagating DNA, such as transposons and bacteriophages. In contrast, obligate intracellular bacteria have small genomes with a low content of repeated sequences and no or few genetic parasites. In extreme cases, such as in the 650 kb-genomes of aphid endosymbionts of the genus Buchnera all repeated sequences above 200bp have been eliminated. We speculate that the initial downsizing of the genomes of obligate symbionts and parasites occurred by homologous recombination at repeated genes, leading to the loss of large blocks of DNA as well as to the consumption of repeated sequences. Further sequence elimination in these small genomes seems primarily to result from the accumulation of short deletions within genic sequences. This process may lead to temporary increases in the genomic content of pseudogenes and 'junk' DNA. We discuss causes and long-term consequences of extreme genome size reductions in obligate intracellular bacteria.

    National Category
    Biochemistry and Molecular Biology
    Identifiers
    urn:nbn:se:uu:diva-89693 (URN)12188042 (PubMedID)
    Available from: 2002-03-06 Created: 2002-03-06 Last updated: 2017-12-14Bibliographically approved
    7. Rickettsia: The highly rearranged cousin of mitochondria
    Open this publication in new window or tab >>Rickettsia: The highly rearranged cousin of mitochondria
    2001 In: Recent Res. Dev. Microbiol., Vol. 5, p. 321-329Article in journal (Refereed) Published
    Identifiers
    urn:nbn:se:uu:diva-89694 (URN)
    Available from: 2002-03-06 Created: 2002-03-06Bibliographically approved
  • 6.
    Andersson, Hans Ola
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Evolutionary Biology.
    Structure-aided design of antiviral drugs: Application of the method on HIV-1 protease and SIV reverse transcriptase1999Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Many efforts have been made to control the AIDS epidemic. Extensive studies have been done on the biology, biochemistry, and structural biology of HIV in the search for antiviral drugs. The viral-encoded enzymes reverse transcriptase and protease have been main targets for drug design.

    Our study on the HIV-1 protease involves the X-ray structure determination of ten complexes with C-terminally duplicated linear inhibitors and two complexes with C2-symmetric cyclic inhibitors. The structural study of the HIV-1 protease/linear inhibitors revealed several interesting properties of the protease, such as the flexibility of S2/S2' subsites, and the presence of coupled and symmetry restricted adaptation of the inhibitor binding subsites. We also found that the inhibitors adopted specific asymmetric conformation of their central parts, where only one of the gemdiol-hydroxyls is pointing toward the catalytic aspartates. The study of the C2-symmetric cyclic inhibitors showed that despite our efforts to promote a symmetric binding of the sulfamide compound, it seems prone to bind non-symmetrically. Our research has resulted in several highly competent inhibitor compounds.

    The work on sooty mangabey SIV reverse transcriptase (SIVsm RT) involves the expression,purification, characterization and studies of inhibition. A simple and efficient large-scalepreparation method was developed for SIVsm RT, in which processing of the p65/p65homodimer to the p65/p51 heterodimer was done with HIV-1 protease. The catalyticproperties of SIVsm RT were characterized. The sensitivity toward non-nucleoside inhibitorsNNI's) of SIVsm RT was distinct from HIV-1. By screening an inhibitor-library, two leadcompounds, MSK-046 and MSK-076 (IC50-values of ~10 µ), belonging to the PETT-serieswere identified.

  • 7.
    Andersson, Jan O.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Evolutionary Biology.
    Molecular evolutionary studies of genome degradation in bacteria1999Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The genus Rickettsia belongs to the α-proteobacteria and consists of obligate intracellular bacteria, which often are pathogenic for humans. All Rickettsia have small genomes, highly adapted to an intracellular lifestyle. However, the ancestors of Rickettsia were most likely free-living organisms with substantially larger genomes, This thesis is a study of the reductive evolutionary processes by which Rickettsia has adapted to a life inside eukaryotic cells.

    The Rickettsia prowazekii genome sequence confirmed the close phylogenetic relationship between the genus Rickettsia and the mitochondria. In addition, 12 putative pseudogenes and an unusually large fraction of non-coding DNA (24%) were identified. Analysis of the metK genomic region in different Rickettsia species identified metK as a pseudogene in all but two lineages. The pattern of mutations indicated that the pseudogenes are no longer under purfying selection, and that metK was inactivated several times independently in different lineages. Similar patterns were found in many other Rickettsia pseudogenes, revealing an ongoing genome degradation process in the Rickettsia.

    Analysis of neutrally evolving pseudogenes showed that deletions dominate over insertions, and that there is a mutational bias towards A+T nucleotides, in the Rickettsia genomes. In agreement, the long intergenic regions in the R. prowazekii genome have a decreased G+C content. Several of these regions showed sequence homology to genes in orthologous positions in other Rickettsia genomes, which indicated that the long intergenic regions represent old genes that are disappearing from the genome.

    The ancestor of the two major Rickettsia groups may have encoded 200-300 additional genes compared to R. prowazekii. Differential loss of mostly genus specific genes during the evolution resulted in the present-day Rickettsia genomes. Currently, Rickettsia inactivates genes at a higher than they are eliminated from the genome by fixation of deletions.

  • 8.
    Andersson, Marie
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
    Cellular transport and secretion of the cyanobacterial neurotoxin BMAA into milk and egg: Implications for developmental neurotoxicity2015Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The cyanobacterial amino acid β-N-methylamino-L-alanine (BMAA) is a neurotoxin implicated in the etiology of neurodegenerative diseases. Cyanobacteria are cosmopolitan organisms present in various environments. BMAA can cause long-term neurodegenerative alterations in rats exposed during the neonatal period, a period that corresponds to the last trimester and the first few years of life in humans. As BMAA has been reported to be bioaccumulated in the aquatic food chain and detected in mussels, crayfish and fish used for human consumption, the main aim of this thesis has been to investigate the final step in the mammalian food-chain, i.e. the transfer of BMAA into breast milk.

    Autoradiographic imaging and mass spectrometry analysis showed an enantiomer-selective uptake of BMAA and that the neurotoxin was transferred from lactating mice and rat, via the milk, to the brain of the nursed pups. The results show that transport of BMAA may be disproportional to dose. In addition, BMAA was found present both as free amino acid and tightly associated to proteins in rat brains. Surprisingly, however, no association to milk proteins was found. In vitro studies of murine (HC11) and human (MCF7) mammary epithelial cells suggest that BMAA can pass the human mammary epithelium into milk. Additional transport studies on human intestinal, glioblastoma and neuroblastoma cells showed that L-BMAA was consistently favored over D-BMAA and that the transport was mediated by several amino acid transporters. We also demonstrated that egg-laying quail transfer BMAA to its offspring by deposition in the eggs, particularly in the yolk but also in the albumen. Furthermore, comparative analysis of carboxyl- and methyl-labeled [14C]-BMAA suggested that BMAA was not metabolized to a large degree.

    Altogether, the results indicate that BMAA can be transferred from mothers, via the milk, to the brain of nursed human infants. Determinations of BMAA in mothers’ milk and cows’ milk are therefore warranted. We also propose that birds’ eggs could be an additional source of BMAA exposure in humans. It might therefore be of concern that mussels are increasingly used as feed in commercial egg production.

    List of papers
    1. Maternal Transfer of the Cyanobacterial Neurotoxin beta-N-Methylamino-L-Alanine (BMAA) via Milk to Suckling Offspring
    Open this publication in new window or tab >>Maternal Transfer of the Cyanobacterial Neurotoxin beta-N-Methylamino-L-Alanine (BMAA) via Milk to Suckling Offspring
    Show others...
    2013 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 10, p. e78133-Article in journal (Refereed) Published
    Abstract [en]

    The cyanobacterial neurotoxin beta-N-methylamino-L-alanine (BMAA) has been implicated in the etiology of neurodegenerative disease and proposed to be biomagnified in terrestrial and aquatic food chains. We have previously shown that the neonatal period in rats, which in humans corresponds to the last trimester of pregnancy and the first few years of age, is a particularly sensitive period for exposure to BMAA. The present study aimed to examine the secretion of C-14-labeled L-and D-BMAA into milk in lactating mice and the subsequent transfer of BMAA into the developing brain. The results suggest that secretion into milk is an important elimination pathway of BMAA in lactating mothers and an efficient exposure route predominantly for L-BMAA but also for D-BMAA in suckling mice. Following secretion of [C-14] L-BMAA into milk, the levels of [C-14] L-BMAA in the brains of the suckling neonatal mice significantly exceeded the levels in the maternal brains. In vitro studies using the mouse mammary epithelial HC11 cell line confirmed a more efficient influx and efflux of L-BMAA than of D-BMAA in cells, suggesting enantiomer-selective transport. Competition experiments with other amino acids and a low sodium dependency of the influx suggests that the amino acid transporters LAT1 and LAT2 are involved in the transport of L-BMAA into milk. Given the persistent neurodevelopmental toxicity following injection of L-BMAA to neonatal rodent pups, the current results highlight the need to determine whether BMAA is enriched mother's and cow's milk.

    National Category
    Natural Sciences
    Identifiers
    urn:nbn:se:uu:diva-211448 (URN)10.1371/journal.pone.0078133 (DOI)000326037000089 ()
    Available from: 2013-11-27 Created: 2013-11-25 Last updated: 2017-12-06Bibliographically approved
    2. Transfer of developmental neurotoxin beta-N-methylamino-L-alanine (BMAA) via milk to nursed offspring: Studies by mass spectrometry and image analysis
    Open this publication in new window or tab >>Transfer of developmental neurotoxin beta-N-methylamino-L-alanine (BMAA) via milk to nursed offspring: Studies by mass spectrometry and image analysis
    2016 (English)In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 258, p. 108-114Article in journal (Refereed) Published
    Abstract [en]

    The cyanobacterial non-proteinogenic amino acid beta-N-methylamino-L-alanine (BMAA) is proposed to be involved in the etiology of amyotrophic lateral sclerosis/parkinsonism dementia complex. When administered as single doses to neonatal rats, BMAA gives rise to cognitive and neurodegenerative impairments in the adult animal. Here, we employed mass spectrometry (LC-MS/MS) and autoradiographic imaging to examine the mother-to-pup transfer of BMAA in rats. The results show that unchanged BMAA was secreted into the milk and distributed to the suckling pups. The concentration of BMAA in pup stomach milk and the neonatal liver peaked after 8 h, while the concentration in the pup brain increased throughout the study period. About 1 and 6% of the BMAA recovered from adult liver and brain were released following hydrolysis, suggesting that this fraction was associated with protein. No association to milk protein was observed. Injection of rat pups with [methyl-C-14]-L-BMAA or [carboxyl-C-14]-L-BMAA resulted in highly similar distribution patterns, indicating no or low metabolic elimination of the methylamino- or carboxyl groups. In conclusion, BMAA is transported as a free amino acid to rat milk and suckling pups. The results strengthen the proposal that mothers' milk could be a source of exposure for BMAA in human infants. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

    Keywords
    BMAA; Cyanobacterial neurotoxin, kinetics; Milk secretion; Developmental neurotoxicity; Mother-to-offspring transfer
    National Category
    Developmental Biology
    Identifiers
    urn:nbn:se:uu:diva-265847 (URN)10.1016/j.toxlet.2016.06.015 (DOI)000381648300012 ()27320960 (PubMedID)
    Projects
    Milk, secretion, BMAA, beta-N-methylamino-L-alanine, autoradiography, mass spectrometry
    Funder
    Swedish Research Council Formas
    Available from: 2015-11-03 Created: 2015-11-03 Last updated: 2017-05-12Bibliographically approved
    3. Potential transfer of neurotoxic amino acid beta-N-methylamino-L-alanine (BMAA) from mother to infant during breast-feeding: Predictions from human cell lines
    Open this publication in new window or tab >>Potential transfer of neurotoxic amino acid beta-N-methylamino-L-alanine (BMAA) from mother to infant during breast-feeding: Predictions from human cell lines
    2017 (English)In: Toxicology and Applied Pharmacology, ISSN 0041-008X, E-ISSN 1096-0333, Vol. 320, p. 40-50Article in journal (Refereed) Published
    Abstract [en]

    β-N-methylamino-alanine (BMAA) is a non-protein amino acid produced by cyanobacteria, diatoms and dinoflagellates. BMAA has potential to biomagnify in a terrestrial food chain, and to bioaccumulate in fish and shellfish. We have reported that administration of [14C]l-BMAA to lactating mice and rats results in a mother to off-spring transfer via the milk. A preferential enantiomer-specific uptake of [14C]l-BMAA has also been demonstrated in differentiated murine mammary epithelium HC11 cells. These findings, together with neurotoxic effects of BMAA demonstrated both in vitro and in vivo, highlight the need to determine whether such transfer could also occur in humans. Here, we used four cell lines of human origin to examine and compare the transport of the two BMAA enantiomers in vitro. The uptake patterns of [14C]l- and [14C]d-BMAA in the human mammary MCF7 cell line were in agreement with the results in murine HC11 cells, suggesting a potential secretion of BMAA into human breast milk. The permeability coefficients for both [14C]l- and [14C]d-BMAA over monolayers of human intestinal Caco2 cells supported an efficient absorption from the human intestine. As a final step, transport experiments confirmed that [14C]l-and [14C]d-BMAA can be taken up by human SHSY5Y neuroblastoma cells and even more efficiently by human U343 glioblastoma cells. In competition experiments with various amino acids, the ASCT2 specific inhibitor benzylserine was the most effective inhibitor of [14C]l-BMAA uptake tested here. Altogether, our results suggest that BMAA can be transferred from an exposed mother, via the milk, to the brain of the nursed infant.

    Place, publisher, year, edition, pages
    Elsevier, 2017
    Keywords
    BMAA, Cellular transport, Amino acid transporters, Breast milk, Neurodegeneration
    National Category
    Cell Biology Developmental Biology
    Research subject
    Biology with specialization in Environmental Toxicology
    Identifiers
    urn:nbn:se:uu:diva-265857 (URN)10.1016/j.taap.2017.02.004 (DOI)000396798200006 ()28174119 (PubMedID)
    Funder
    Swedish Research Council Formas
    Available from: 2015-11-03 Created: 2015-11-03 Last updated: 2017-05-02Bibliographically approved
    4. Protein association of the neurotoxin and non-protein amino acid BMAA (beta-N-methylamino-L-alanine) in the liver and brain following neonatal administration in rats
    Open this publication in new window or tab >>Protein association of the neurotoxin and non-protein amino acid BMAA (beta-N-methylamino-L-alanine) in the liver and brain following neonatal administration in rats
    Show others...
    2014 (English)In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 226, no 1, p. 1-5Article in journal (Refereed) Published
    Abstract [en]

    The environmental neurotoxin beta-N-methylamino-L-alanine (BMAA) is not an amino acid that is normally found in proteins. Our previous autoradiographic study of H-3-labeled BMAA in adult mice unexpectedly revealed a tissue distribution similar to that of protein amino acids. The aim of this study was to characterize the distribution of free and protein-bound BMAA in neonatal rat tissues following a short exposure using autoradiographic imaging and ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The autoradiographic imaging of C-14-L-BMAA demonstrated a distinct uptake of radioactivity that was retained following acid extraction in tissues with a high rate of cell turnover and/or protein synthesis. The UHPLC-MS/MS analysis conclusively demonstrated a dose-dependent increase of protein-associated BMAA in neonatal rat tissues. The level of protein-associated BMAA in the liver was more than 10 times higher than that in brain regions not fully protected by the blood-brain barrier which may be due to the higher rate of protein synthesis in the liver. In conclusion, this study demonstrated that BMAA was associated with rat proteins suggesting that BMAA may be mis-incorporated into proteins. However, protein-associated BMAA seemed to be cleared over time, as none of the samples from adult rats had any detectable free or protein-associated BMAA.

    Keywords
    ALS/PDC, Cyanobacteria, Autoradiography, Mass spectrometry, Misincorporation, N-(2-aminoethyl) glycine
    National Category
    Medical and Health Sciences Natural Sciences
    Identifiers
    urn:nbn:se:uu:diva-222718 (URN)10.1016/j.toxlet.2014.01.027 (DOI)000332409000001 ()24472610 (PubMedID)
    Funder
    Swedish Research Council Formas
    Available from: 2014-04-17 Created: 2014-04-14 Last updated: 2017-06-30Bibliographically approved
    5. Deposition of cyanobacterial neurotoxin beta-N-methylamino-L-alanine (L-BMAA) in birds' egg: A potential source of BMAA exposure in humans
    Open this publication in new window or tab >>Deposition of cyanobacterial neurotoxin beta-N-methylamino-L-alanine (L-BMAA) in birds' egg: A potential source of BMAA exposure in humans
    (English)Manuscript (preprint) (Other academic)
    Keywords
    BMAA, beta-N-methylamino-L-alanine, quail, metabolism, autoradiography
    National Category
    Developmental Biology
    Research subject
    Biology with specialization in Environmental Toxicology
    Identifiers
    urn:nbn:se:uu:diva-265859 (URN)
    Funder
    Swedish Research Council Formas
    Available from: 2015-11-03 Created: 2015-11-03 Last updated: 2016-01-13
  • 9.
    Andersson, Marie
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
    Ersson, Lisa
    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 Organismal Biology, Environmental toxicology.
    Bergström, Ulrika
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
    Potential transfer of neurotoxic amino acid beta-N-methylamino-L-alanine (BMAA) from mother to infant during breast-feeding: Predictions from human cell lines2017In: Toxicology and Applied Pharmacology, ISSN 0041-008X, E-ISSN 1096-0333, Vol. 320, p. 40-50Article in journal (Refereed)
    Abstract [en]

    β-N-methylamino-alanine (BMAA) is a non-protein amino acid produced by cyanobacteria, diatoms and dinoflagellates. BMAA has potential to biomagnify in a terrestrial food chain, and to bioaccumulate in fish and shellfish. We have reported that administration of [14C]l-BMAA to lactating mice and rats results in a mother to off-spring transfer via the milk. A preferential enantiomer-specific uptake of [14C]l-BMAA has also been demonstrated in differentiated murine mammary epithelium HC11 cells. These findings, together with neurotoxic effects of BMAA demonstrated both in vitro and in vivo, highlight the need to determine whether such transfer could also occur in humans. Here, we used four cell lines of human origin to examine and compare the transport of the two BMAA enantiomers in vitro. The uptake patterns of [14C]l- and [14C]d-BMAA in the human mammary MCF7 cell line were in agreement with the results in murine HC11 cells, suggesting a potential secretion of BMAA into human breast milk. The permeability coefficients for both [14C]l- and [14C]d-BMAA over monolayers of human intestinal Caco2 cells supported an efficient absorption from the human intestine. As a final step, transport experiments confirmed that [14C]l-and [14C]d-BMAA can be taken up by human SHSY5Y neuroblastoma cells and even more efficiently by human U343 glioblastoma cells. In competition experiments with various amino acids, the ASCT2 specific inhibitor benzylserine was the most effective inhibitor of [14C]l-BMAA uptake tested here. Altogether, our results suggest that BMAA can be transferred from an exposed mother, via the milk, to the brain of the nursed infant.

  • 10.
    Andersson, Marie
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
    Karlsson, Oskar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. Karolinska Inst, Dept Clin Neurosci, Ctr Mol Med, SE-17176 Stockholm, Sweden.
    Banack, Sandra
    Inst Ethnomed, POB 3464, Jackson, WY 83001 USA.
    Brandt, Ingvar
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
    Transfer of developmental neurotoxin beta-N-methylamino-L-alanine (BMAA) via milk to nursed offspring: Studies by mass spectrometry and image analysis2016In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 258, p. 108-114Article in journal (Refereed)
    Abstract [en]

    The cyanobacterial non-proteinogenic amino acid beta-N-methylamino-L-alanine (BMAA) is proposed to be involved in the etiology of amyotrophic lateral sclerosis/parkinsonism dementia complex. When administered as single doses to neonatal rats, BMAA gives rise to cognitive and neurodegenerative impairments in the adult animal. Here, we employed mass spectrometry (LC-MS/MS) and autoradiographic imaging to examine the mother-to-pup transfer of BMAA in rats. The results show that unchanged BMAA was secreted into the milk and distributed to the suckling pups. The concentration of BMAA in pup stomach milk and the neonatal liver peaked after 8 h, while the concentration in the pup brain increased throughout the study period. About 1 and 6% of the BMAA recovered from adult liver and brain were released following hydrolysis, suggesting that this fraction was associated with protein. No association to milk protein was observed. Injection of rat pups with [methyl-C-14]-L-BMAA or [carboxyl-C-14]-L-BMAA resulted in highly similar distribution patterns, indicating no or low metabolic elimination of the methylamino- or carboxyl groups. In conclusion, BMAA is transported as a free amino acid to rat milk and suckling pups. The results strengthen the proposal that mothers' milk could be a source of exposure for BMAA in human infants. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

  • 11.
    Andersson, Marie
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
    Karlsson, Oskar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Bergström, Ulrika
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
    Brittebo, Eva B.
    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 Organismal Biology, Environmental toxicology.
    Correction: Maternal Transfer of the Cyanobacterial Neurotoxin β-N-Methylamino-L-Alanine (BMAA) via Milk to Suckling Offspring2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 10, article id e78133Article in journal (Refereed)
  • 12.
    Andersson, Marie
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
    Karlsson, Oskar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmacy.
    Brandt, Ingvar
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
    Deposition of cyanobacterial neurotoxin beta-N-methylamino-L-alanine (L-BMAA) in birds' egg: A potential source of BMAA exposure in humansManuscript (preprint) (Other academic)
  • 13.
    Andersson, Måns S.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Evolutionary Biology.
    Physiological trade-offs in reproduction and condition dependence of a secondary sexual trait2001Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This thesis examines parental condition, how it is traded off against reproduction and how it is displayed in a secondary sexual trait. The studies were performed on nest-box breeding collared flycatchers Ficedula albicollis on the island of Gotland, in the Baltic Sea. Early breeding and high fitness were found to be associated with high levels of glycosylated haemoglobin possibly governed by migratory exertion and infectious disease. In order to test if immune function is expressed in secondary sexual traits and how it is traded off against reproductive effort a series of experiments were performed, in which birds were challenged with an antigen, via a vaccine containing neutralised paramyxovirus. The forehead patch of the male collared flycatcher serves as a badge of status and is under sexual selection. Good condition, as reflected in strong immune response and low levels of blood parasites was found to be associated with bigger patch size. Patch size was also found to vary in size within the same breeding season in a pattern predictable from immune response data. Immune response, in itself, was found to be costly in terms of reduced survival, confirming that trade-offs involving suppression of immune response may increase fitness. Mating effort was found to be traded off against immune function and moult. Experimental brood size manipulations revealed a trade-off females between number of offspring and immune function. Thus I suggest a set of parameters useful for condition estimation. I also show that immune response is costly and, second, that pathogen resistance probably plays an important role in the shaping of secondary sexual traits and life-history decisions.

  • 14.
    Andrae, Johanna
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology.
    Betsholtz, Christer
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology.
    Gouveia, Maria Leonor Seguardo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology.
    PDGFR alpha signaling is required for alveolar development in the mouse lung2017In: Mechanisms of Development, ISSN 0925-4773, E-ISSN 1872-6356, Vol. 145, p. S147-S147Article in journal (Other academic)
  • 15.
    Archer, Amena
    et al.
    Karolinska Institutet.
    Kitambi, Satish Srinivas
    Karolinska Institutet.
    Hallgren, Stefan
    Södertörns Universitet.
    Pedrelli, Mateo
    Karolinska Institutet.
    Olsén, Håkan
    Södertörns Högskola.
    Agneta, Mode
    Karolinska Institutet.
    Gustafsson, Jan-Åke
    Karolinska Institutet.
    The liver X receptor (lxr) governs lipid homeostasis in zebrafish during development2012In: Open Journal of Endocrine and Metabolic Diseases, ISSN 2165-7432, Vol. 2, p. 74-81Article in journal (Refereed)
    Abstract [en]

    The liver X-receptors (LXRs) act as cholesterol sensors and participate in the regulation of lipid and cholesterol metabolism. The objective of this study was to determine the role of LXR during development using the zebrafish model. By in situ hybridization we showed distinct expression of lxr in the brain and the retina in the developing and adult zebrafish. Lxr ligand activation affected the expression of genes involved in lipid metabolism in zebrafish adult brain and eye as well as in zebrafish embryos. Morpholino knock down of lxr resulted in an overall impaired lipid deposition as determined by oil red O staining particularly in the head and around the eyes, and to significantly elevated levels of both total and free cholesterol in the yolk of lxr morphant embryos. The expression of genes involved in lipid and cholesterol metabolism was also changed in the lxr morphants. Furthermore, alcian blue staining revealed malformation of the pharyngeal skeleton in the lxr morphant. Our data show that lxr is an important component of the regulatory network governing the lipid homeostasis during zebrafish development, which in turn may support a role of lxr for normal development of the central nervous sytem, including the retina.

  • 16.
    Aresh, Bejan
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Genetics.
    Peuckert, Christiane
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Evolution and Developmental Biology.
    Dissection and Culture of Mouse Embryonic Kidney2017In: Journal of Visualized Experiments, ISSN 1940-087X, E-ISSN 1940-087X, no 123, article id e55715Article in journal (Refereed)
    Abstract [en]

    The goal of this protocol is to describe a method for the dissection, isolation, and culture of mouse metanephric rudiments. During mammalian kidney development, the two progenitor tissues, the ureteric bud and the metanephric mesenchyme, communicate and reciprocally induce cellular mechanisms to eventually form the collecting system and the nephrons of the kidney. As mammalian embryos grow intrauterine and therefore are inaccessible to the observer, an organ culture has been developed. With this method, it is possible to study epithelial-mesenchymal interactions and cellular behavior during kidney organogenesis. Furthermore, the origin of congenital kidney and urogenital tract malformations can be investigated. After careful dissection, the metanephric rudiments are transferred onto a filter that floats on culture medium and can be kept in a cell culture incubator for several days. However, one must be aware that the conditions are artificial and could influence the metabolism in the tissue. Also, the penetration of test substances could be limited due to the extracellular matrix and basal membrane present in the explant. One main advantage of organ culture is that the experimenter can gain direct access to the organ. This technology is cheap, simple, and allows a large number of modifications, such as the addition of biologically active substances, the study of genetic variants, and the application of advanced imaging techniques.

  • 17.
    Arvola, Marie
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Evolutionary Biology.
    Immunological aspects of maternal-foetal interactions in mice2001Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Mammalian pregnancy is an immunological paradox. The foetus, which expresses both paternal and maternal cell-surface molecules, has to be protected from rejection by the maternal immune system. At the same time, the mother has to have an efficient immune defence and must provide her offspring with antibodies.

    The first part of this thesis investigates some of the mechanisms involved in the foetal avoidance of maternal rejection reactions. Placental absence of MHC class II expression, as well as a bias for Th2-cytokines at the maternal-foetal interface are suggested to be important for foetal survival. The results showed that placental MHC class II expression cannot be induced in vivo. Transfections of trophoblast cells with MHC class II genes, however, resulted in detectable MHC class II cell-surface expression, indicating that a post-transcriptional block does not exist in these cells.

    By using IL-4- and IL-10-double deficient mice, it was shown that neither maternal nor foetal expression of these cytokines were crucial for completion of allogeneic pregnancy.

    In the second part of the thesis, the effect of transmission of immunoglobulin G (IgG) from the mother to the offspring was studied. It was observed that viable maternal Ig-secreting cells occasionally infiltrated the B cell-deficient offspring and remained functional for long periods. In this study "green fluorescent mice" were used as a tool. Furthermore, neonatal ingestion of wild type milk increased the survival of adoptively transferred B-lineage cells in B cell-deficient mice, suggesting that suckling of IgG-containing milk could be used to facilitate B cell-reconstitution in B cell-deficient mice. Finally, results from studies on normal mice showed that absence of maternal IgG-transmission during their neonatal development resulted in elevated serum-IgG production, as well as enhanced immune reactions upon immunisations in adult life. This showed that maternal IgG can have long-term immunoregulatory effects in the offspring.

  • 18.
    Attwood, Misty M.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Krishnan, Arunkumar
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Sällman Almén, Markus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Schiöth, Helgi B.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Functional Pharmacology.
    Highly diversified expansions shaped the evolution of membrane bound proteins in metazoans2017In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 12387Article in journal (Refereed)
    Abstract [en]

    The dramatic increase in membrane proteome complexity is arguably one of the most pivotal evolutionary events that underpins the origin of multicellular animals. However, the origin of a significant number of membrane families involved in metazoan development has not been clarified. In this study, we have manually curated the membrane proteomes of 22 metazoan and 2 unicellular holozoan species. We identify 123,014 membrane proteins in these 24 eukaryotic species and classify 86% of the dataset. We determine 604 functional clusters that are present from the last holozoan common ancestor (LHCA) through many metazoan species. Intriguingly, we show that more than 70% of the metazoan membrane protein families have a premetazoan origin. The data show that enzymes are more highly represented in the LHCA and expand less than threefold throughout metazoan species; in contrast to receptors that are relatively few in the LHCA but expand nearly eight fold within metazoans. Expansions related to cell adhesion, communication, immune defence, and developmental processes are shown in conjunction with emerging biological systems, such as neuronal development, cytoskeleton organization, and the adaptive immune response. This study defines the possible LHCA membrane proteome and describes the fundamental functional clusters that underlie metazoan diversity and innovation.

  • 19.
    Bahrami, Fariba
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Evolutionary Biology.
    Methylsulphonyl-chlorobenzenes and the olfactory system: Comparative toxicity of the 2,5- and 2,6-dichlorinated isomers in mice2000Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Methyl sulphone metabolites of chlorinated aryl hydrocarbons are persistentenvironmental pollutants that can bioaccumulate in animals and humans. Little is known about the toxicological effects of these metabolites and this thesis is an attempt to increase this limited knowledge. Tissue-binding, toxicity and neuro-behavioural effects of methylsulphonyl-2,6dichlorobenzene [2,6-(diCl-MeSO2-B)] and methylsulphonyl-2,5-dichlorobenzene [2,5-(diCl-MeSO2-B)] were examined on mice.

    Both substances resulted in a strong uptake in the olfactory mucosa (OM). Only 2,6-(diCl-MeSO2-B) induced toxicity in the OM, originating from a primary lesion in the Bowman's glands (BG). An in situ CYP-catalysed activation of 2,6-(diCl-MeSO2-B) seems to occur in the BG giving rise to reactive intermediates which either conjugate with glutathione or induce local toxicity. Subsequent secondary lesions in the OM include: severe degenerationof the neuroepithelium, fibrosis, ossification and polyposis. These effects resulted from a single ip dose and were permanent. Long lasting induction of GFAP in the olfactory bulb (OB) and behavioural deficits were also observed and considered to be caused by damaged olfactory neurons and/or metabolites translocated to the OB. Although the OM was more damaged in male mice, acquisition deficits occurred only in female mice.

    2,5-(diCl-MeSO2-B) did not induce OM toxicity, GFAP or learning deficits in either sex. However, observed motor activity responses indicate that, although 2,5-(diCl-MeSO2-B) is not olfacto-toxic, it is neuro-toxic.

    1,3-Dichloro-, 1,4-dichloro- or 1,2,3-trichloro-benzene did not induce damage in the OM indicating that an electron withdrawing substituent in the primary position and 2,6-positioned chlorine atoms is a structural requirement for OM toxicity. Persistent, dose-, time-, tissue- and sex-dependent effects on the olfactory system induced by 2,6-(diCl-MeS2-B) together with the lack of lesions in the OM or brain by 2,5-(diCl-MeSO2-B), makes this chemical pair a reliable and versatile tool for olfactory research.

  • 20. Barton, S C
    et al.
    Arney, K L
    Shi, Wei
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Animal Development and Genetics.
    Niveleau, A
    Fundele, Reinald
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Animal Development and Genetics.
    Surani, M A
    Haaf, T
    Genome-wide methylation patterns in normal and uniparental early mouse embryos2001In: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 10, no 26, p. 2983-7Article in journal (Refereed)
  • 21.
    Bekele, Tesfaye
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Evolutionary Biology.
    Plant Population Dynamics of Dodonaea angustifolia and Olea europaea ssp. cuspidata in Dry Afromontane Forests of Ethiopia2000Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Human disturbance has led to excessive deforestation and to a very limited forest cover in the Afromontane zone of Ethiopia, which forms a large part of the country. Thus urgent conservation measures are required to ameliorate the situation. Understanding the natural regeneration processes and the dynamics of plant populations of tree and shrub species has a practical application in the restoration of these habitats.

    The present study focuses on the population dynamics and regeneration of an early successional shrub Dodonaea angustifolia and a late successional tree Olea europaea ssp. cuspidata in southern Wello, Ethiopia. Population structure and dynamics, regeneration and seed banks in dry Afromontane habitats were considered.

    For both species, three population structure patterns were identified: 1) high density, reversed J-shape structure with many seedlings and few large individuals, 2) lower density, unimodal structure with higher proportions of plants of intermidiate size, 3) high density with higher proportions of large plants , in some cases bimodal with small and large individuals. Vegetation type and protection time were found to have a significant effect on the population structure of both species. Dodonaea can establish itself on degraded land, once the disturbance has ceased

    Projection matrix analysis on observations from permanent plots in Dodonaea populations in protected and unprotected sites resulted in one declining population, and one increasing in the protected site and declining populations at the unprotected site. The overall projected growth rate in Dodonaea calculated from a pooled matrix indicated positive population growth. The factors influencing the population growth, recruitment and survival are discussed.

    The persistence of Olea populations seems to depend on the more stable environmental conditions in later successional stages of forest vegetation. There are possibilities of natural regeneration of Olea if regenerating individuals still occur in the area. Rainfall seasonality is a dominant factor in regulating establishment, recruitment, survival and growth, particularly during the seedling stage. Moreover, shade and herbivory are factors that need consideration. Since Olea grows better under shade than in the open sun, successful regeneration for this species relies on shade from other plants and on protection from grazing, at least during the seedling stage.

    Most of the species that germinated from the seed banks were herbs and grasses with very few shrub and tree species. There was low correspondence between species composition of the seed banks and that of the standing vegetation.

    Spatial and temporal variation in demographic parameters among populations of Dodonaea and Olea can be attributed to human and environmental influence. Under protection, both Dodonaea and Olea seem to have a possibility to regenerate naturally. Further research should consider factors mentioned in detailed investigations of other dominant Afromontane forest species.

  • 22.
    Bentley, Katie
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Vascular Biology. Harvard Med Sch, Beth Israel Deaconess Med Ctr, Computat Biol Lab, Boston, MA USA..
    Chakravartula, Shilpa
    Harvard Med Sch, Beth Israel Deaconess Med Ctr, Computat Biol Lab, Boston, MA USA..
    The temporal basis of angiogenesis2017In: Philosophical Transactions of the Royal Society of London. Biological Sciences, ISSN 0962-8436, E-ISSN 1471-2970, Vol. 372, no 1720, p. 1-11, article id 20150522Article in journal (Refereed)
    Abstract [en]

    The process of new blood vessel growth (angiogenesis) is highly dynamic, involving complex coordination of multiple cell types. Though the process must carefully unfold over time to generate functional, well-adapted branching networks, we seldom hear about the time-based properties of angiogenesis, despite timing being central to other areas of biology. Here, we present a novel, time-based formulation of endothelial cell behaviour during angiogenesis and discuss a flurry of our recent, integrated in silico/in vivo studies, put in context to the wider literature, which demonstrate that tissue conditions can locally adapt the timing of collective cell behaviours/decisions to grow different vascular network architectures. A growing array of seemingly unrelated 'temporal regulators' have recently been uncovered, including tissue derived factors (e.g. semaphorins or the high levels of VEGF found in cancer) and cellular processes (e.g. asymmetric cell division or filopodia extension) that act to alter the speed of cellular decisions to migrate. We will argue that 'temporal adaptation' provides a novel account of organ/disease-specific vascular morphology and reveals 'timing' as a new target for therapeutics. We therefore propose and explain a conceptual shift towards a 'temporal adaptation' perspective in vascular biology, and indeed other areas of biology where timing remains elusive. This article is part of the themed issue 'Systems morphodynamics: understanding the development of tissue hardware'.

  • 23. Benton, Jeanne
    et al.
    Kery, Rachel
    Li, Jingjing
    Noonin, Chadanat
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Comparative Physiology.
    Söderhäll, Irene
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Comparative Physiology.
    Beltz, Barbara
    Cells from the Immune System Generate Adult-Born Neurons in Crayfish2014In: Developmental Cell, ISSN 1534-5807, E-ISSN 1878-1551, Vol. 30, no 3, p. 322-333Article in journal (Refereed)
    Abstract [en]

    Neurogenesis is an ongoing process in the brains of adult decapod crustaceans. However, the first-generation precursors that produce adult-born neurons, which reside in a neurogenic niche, are not self-renewing in crayfish and must be replenished. The source of these neuronal precursors is unknown. Here, we report that adult-born neurons in crayfish can be derived from hemocytes. Following adoptive transfer of 5-ethynyl-2′-deoxyuridine (EdU)-labeled hemocytes, labeled cells populate the neurogenic niche containing the first-generation neuronal precursors. Seven weeks after adoptive transfer, EdU-labeled cells are located in brain clusters 9 and 10 (where adult-born neurons differentiate) and express appropriate neurotransmitters. Moreover, the number of cells composing the neurogenic niche in crayfish is tightly correlated with total hemocyte counts (THCs) and can be manipulated by raising or lowering THC. These studies identify hemocytes as a source of adult-born neurons in crayfish and demonstrate that the immune system is a key contributor to adult neurogenesis.

  • 24.
    Benton, JL
    et al.
    Wellesley Coll, Neurosci. Program, Wellesley.
    Zhang, Y
    Wellesley Coll, Neurosci. Program, Wellesley.
    Söderhäll, Irene
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Comparative Physiology.
    Beltz, BS
    Wellesley Coll, Neurosci. Program, Wellesley, MA 02181 USA .
    The crustacean cytokine astakine-1: a link between adult neurogenesis and hematopoiesis?2012Conference paper (Refereed)
    Abstract [en]

    Adult neurogenesis occurs in the brains of vertebrate and invertebrate species. In the crayfish Procambarus clarkii, neurogenic niches located on the ventral surface of the brain contain the 1st-generation precursors that produce adult-born neurons. These cells divide symmetrically and both daughter cells migrate in streams to proliferation zones in interneuronal cell clusters, where they divide at least one more time. Double-nucleoside labeling has confirmed that the 1st-generation neuronal precursors are not self-renewing. However, previous studies have shown that the niche is not depleted and, further, that niche cell numbers increase throughout the animal’s lifetime (Zhang et al., 2009). Our goal, therefore, is to identify the source of niche cells and in particular the 1st-generation neuronal precursors. Experiments have revealed that hemocytes, and in particular semi-granular cells, are attracted to and incorporated into the niches of dissected intact brains in culture; cell types from other tissues show no affinity for the niche (Benton et al., 2011). Lin et al. (2010) demonstrated that a prokineticin family cytokine, astakine-1, promotes the differentiation and release of semi-granular cells from hematopoietic tissue. In the present studies, we have injected astakine-1 into crayfish and examined subsequent changes in niche cell numbers, as well as BrdU incorporation into cells in the niche, streams and proliferation zones. By 48 hrs following astakine-1 injection, three alterations in the neurogenic system have been demonstrated: (1) increased total numbers of cells in the neurogenic niche compared to saline-injected shams; (2) increased BrdU-incorporation into cells in the niche, streams and proliferation zone in cell cluster 10; (3) increased probability of observing cells within the vascular cavity in the niche, implying that the numbers of cells interacting with the niche is upregulated. These experiments exploring the relationship between the hematopoietic system and adult neurogenesis suggest that cells released from hematopoietic tissues following astakine-1 injection influence the cellular composition of the niche and the rate of BrdU-incorporation into niche cells.

  • 25.
    Berg, Cecilia
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Evolutionary Biology.
    Environmental pollutants and the reproductive system in birds: Developmental effects of estrogenic compounds2000Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    A number of environmental pollutants have been shown to mimick the action of the female sex hormone estrogen and are, therefore, suspected to be responsible for reproductive abnormalities seen in wildlife. Test systems which can be used in hazard and risk assessment of chemicals with estrogenic effects are consequently needed. In this thesis, I propose the avian egg as an in vivo test system for estrogenic compounds. I conclude that malformation of the left testis and the Müllerian ducts (MDs: embryonic oviducts) in avian embryos can be used as endpoints to examine estrogenic activity of chemicals. MD malformation is more easily determined and thereby faster to use as an endpoint than histologically observed feminization of the testis. The usefulness of MD/oviduct malformations as biomarkers for estrogenic effects in wild birds should be considered.

    The environmental pollutants bisphenol A (BPA) and o,p´-DDT induced similar effects as the synthetic estrogens, ethynylestradiol and diethylstilbestrol. BPA caused MD malformations in quail embryos and ovotestis formation in chicken embryos. o,p´-DDT induced MD malformations in both quail and chicken embryos and ovotestis in chicken embryos. The flame retardant, tetrabromobisphenol A did not induce estrogen-like effects in quail or chicken embryos, but showed a relatively high embryolethality.

    Embryonic exposure to estrogen caused persisting malformations of the oviduct, as well as a changed distribution pattern of the enzyme carbonic anhydrase in the shell gland of adult females. Considering the crucial role of carbonic anhydrase in shell formation, such changes could result in decreased shell quality. I propose that eggshell thinning in avian wildlife could reflect a functional malformation in the shell gland that is induced by xeno-estrogens during embryonic development, rather than being caused by exposure of the adult bird to environmental pollutants. This hypothesis opens new possibilities for studying the mechanisms behind contaminant-induced eggshell thinning in birds.

  • 26.
    Berg, Lars M.
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Evolutionary Biology.
    Genetic Disequilibria and the Interpretation of Population Genetic Structure in Daphnia2001Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Understanding the processes that shape the spatial distribution of genetic variation within species is central to the evolutionary study of diversification and demography. Neutral genetic variation reflects past demographic events as well as current demographic characteristics of populations, and the correct interpretation of genetic data requires that the relative impact of these forces can be identified. Details of breeding systems can affect the genetic structure through effects on effective migration rate or on effective population size. Restrictions in recombination rate lead to associations between neutral marker genes and genes under natural selection. Although the effects on genetic structure can be substantial, the process will often be difficult to tell apart from stochastic effects of history or genetic drift, which may suggest erroneous conclusions about demography.

    In cyclically parthenogenetic freshwater invertebrates, which alternate between sexual and asexual reproduction, demographic fluctuations and reliance on diapausing eggs for dispersal enhances neutral genetic differentiation as well as effects of selection on associated genes. Although genetic founder effects are expected to be profound and long-lasting in these species, genetic hitch-hiking may reduce initial strong differentiation rapidly if better adapted genes are introduced by mutation or immigration. Fluctuating environmental conditions have been suggested to generate rapid shifts in the frequencies of clones during the asexual phase. In the presence of egg banks resting in sediments, genetic diversity is stabilised and the importance of migration for differentiation is reduced.

    Studies of unstable and young populations of cyclically parthenogenetic Daphnia pulex showed substantial variation for important fitness traits, within as well as between populations, despite hypothesised recent founder effects. Neutral markers indicated genetic equilibrium, but changes in clonal composition during asexuality disrupted the genetic structure in a manner compatible with local adaptation and exclusion of immigrants. This illustrates that the forces affecting sexual progeny may be markedly different from those shaping the structure among asexual individuals.

  • 27.
    Blixt, Maria
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Neuroscience.
    Hallböök, Finn
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Developmental Neuroscience.
    A regulatory sequence from the retinoid X receptor gamma gene directs expression to horizontal cells and photoreceptors in the embryonic chicken retina2016In: Molecular Vision, ISSN 1090-0535, E-ISSN 1090-0535, Vol. 22, p. 1405-1420Article in journal (Refereed)
    Abstract [en]

    PURPOSE: Combining techniques of episomal vector gene-specific Cre expression and genomic integration using the piggyBac transposon system enables studies of gene expression-specific cell lineage tracing in the chicken retina. In this work, we aimed to target the retinal horizontal cell progenitors. METHODS: A 208 bp gene regulatory sequence from the chicken retinoid X receptor gammagene (RXRgamma208) was used to drive Cre expression. RXRgamma is expressed in progenitors and photoreceptors during development. The vector was combined with a piggyBac "donor" vector containing a floxed STOP sequence followed by enhanced green fluorescent protein (EGFP), as well as a piggyBac helper vector for efficient integration into the host cell genome. The vectors were introduced into the embryonic chicken retina with in ovo electroporation. Tissue electroporation targets specific developmental time points and in specific structures. RESULTS: Cells that drove Cre expression from the regulatory RXRgamma208 sequence excised the floxed STOP-sequence and expressed GFP. The approach generated a stable lineage with robust expression of GFP in retinal cells that have activated transcription from the RXRgamma208 sequence. Furthermore, GFP was expressed in cells that express horizontal or photoreceptor markers when electroporation was performed between developmental stages 22 and 28. Electroporation of a stage 12 optic cup gave multiple cell types in accordance with RXRgamma gene expression in the early retina. CONCLUSIONS: In this study, we describe an easy, cost-effective, and time-efficient method for testing regulatory sequences in general. More specifically, our results open up the possibility for further studies of the RXRgamma-gene regulatory network governing the formation of photoreceptor and horizontal cells. In addition, the method presents approaches to target the expression of effector genes, such as regulators of cell fate or cell cycle progression, to these cells and their progenitor.

  • 28.
    Blom, Henning
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology.
    A new anaspid fish from the middle Silurian Cowie Harbour fish bed of Stonehaven, Scotland 2008In: Journal of Vertebrate Paleontology, ISSN 0272-4634, E-ISSN 1937-2809, Vol. 28, no 3, p. 594-600Article in journal (Refereed)
    Abstract [en]

    A new birkeniid anaspid, Cowielepis ritchiei gen. et sp. nov., from the mid Silurian Cowie Harbour fish bed in Scotland is described on the basis of three specimens. Although sharing characters with various well-known anaspids, it possesses a unique combination of features that justifies the establishment of a new genus. Cowielepis is characterized by a single row of dorsolateral scales and a distinctive skull roof pattern with a large pineal plate and elongated posterior plates. The presence of paired ventrolateral fins in C. ritchiei supports previous suggestions that all anaspids possess such fins, but leaves open the question of homology with the gnathostome pectoral fin.

  • 29.
    Blom, Henning
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Evolutionary Organism Biology.
    Recent Advances in the Origin and Early Radiation of Vertebrates. Arratia, G., Wilson, M. V. H. & Cloutier, R. (eds)2005In: Geological Magazine, ISSN 0016-7568, E-ISSN 1469-5081, Vol. 142, no 6, p. 823-823Article, book review (Other (popular science, discussion, etc.))
  • 30.
    Blom, Henning
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Evolutionary Organism Biology.
    Silurian and Lower Devonian thelodonts and putative chondrichthyans from the Canadian Artic Archipelago. Märss, T., Wilson M. V. H. & Thorsteinsson, R.2007In: Geological Magazine, ISSN 0016-7568, E-ISSN 1469-5081, Vol. 144, no 6, p. 1032-1032Article, book review (Other academic)
  • 31.
    Blom, Henning
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, Palaeobiology, Palaeontology group.
    Vertebrate remains from the Upper Silurian-Lower Devonian of North Greenland1998Licentiate thesis, comprehensive summary (Other academic)
  • 32.
    Bremer, Oskar
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Evolution and Developmental Biology.
    Blom, Henning
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Evolution and Developmental Biology.
    An updated stratigraphic and environmental framework for the distribution of Silurian vertebrates on Gotland2015In: Estonian journal of earth sciences, ISSN 1736-4728, E-ISSN 1736-7557, Vol. 64, no 1, p. 13-18Article in journal (Refereed)
  • 33.
    Brohede, Jesper
    Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Evolutionary Biology.
    Rates and Patterns of Mutation in Microsatellite DNA2003Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Sequence comparisons of orthologous microsatellite loci in cattle and sheep revealed that the substitution rate in microsatellite flanking sequences does not differ from the rate in presumably neutrally evolving intron sequences. This suggests that microsatellites are generally located in regions that are not subjected to selection. Interestingly, a propensity for substitutions to occur in the border region between flanking and repeat sequence was found.

    Pedigree analysis of large numbers of barn swallows revealed extremely high mutation frequencies for the tetranucleotide HrU6 and pentanucleotide HrU10 repeat loci. A detailed analysis showed that both the rate and the pattern of mutation differed significantly between the two loci.

    Further analysis of HrU6 and HrU10 mutations, as well as mutation data for another hypermutable locus (HrU9) in barn swallows, revealed that mutations were more likely to arise in some families than others. This was partly, but probably not only, due to an effect of allele length on mutation rate. The mutation rate was found to vary between colonies of breeding birds, but, overall, not between two different populations.

    Single molecule genotyping of DNA prepared from human sperm cells was used to detect mutations at the tetranucleotide repeat D21S1245. A tenfold difference in mutation rate between alleles was found. Three phylogenetically distinct allele lineages could be defined, which differed significantly in mutation rate. Unexpectedly, the mutation rate was not found to increase with male age.

    Microsatellites are commonly applied in a wide range of genetic contexts including linkage mapping, forensic science and population genetics. Obtaining a detailed picture of the evolution of these tandem repeats is important in order to fully understand how to interpret microsatellite data. In addition, studies of the mechanisms underlying microsatellite mutation will provide insights in the processes that shape the eukaryotic genome.

    This thesis demonstrates that microsatellite evolution is a highly heterogeneous process that is dependent on more factors than was previously thought. As the rate and pattern may vary between loci, caution must therefore be taken when building models to handle microsatellite data.

  • 34.
    Buratovic, Sonja
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental Toxicology.
    Fredriksson, Anders
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental Toxicology.
    Crofton, Kevin
    Neurotoxicology Division, National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. EPA, Research Triangle Park, USA.
    Viberg, Henrik
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental Toxicology.
    Eriksson, Per
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental Toxicology.
    Comparison of single and repeated exposure to low doses of pyrethroids, permethrin and bioallethrin, during neonatal brain development on adult spontaneous behaviour2012Conference paper (Refereed)
    Abstract [en]

    Permethrin and bioallethrin belong to the Type 1 class of pyrethroid pesticides. The primary mechanism of action is interference with nerve membrane sodium channels that results in increased neuronal activity. We have earlier reported on developmental neurotoxic effects after repeated, PND 10 to PND16, neonatal exposure to pyrethroids. The effects were manifested as altered spontaneous behavior, hyperactivity and reduced cognitive function and changes in cholinergic muscarinic/nicotinic receptors in the cerebral cortex of neonatal and adult mice. The present study was undertaken to compare repeated and single exposure to permethrin and bioallethrin during the neonatal brain growth spurt (BGS) on adult spontaneous behavior in a novel home environment. Neonatal NMRI male mice were given permethrin, orally (0.55; 3.3; 6.6 mg/kg bw/day) on PND 10-14, or just a single oral dose of 6.6 mg/kg bw on PND 10. Bioallethrin was given as a single oral dose of 0.7 mg/kg bw on PND 10, and compared to earlier published data on repeated exposure. Mice serving as controls received the 20 % fat emulsion vehicle. Spontaneous behavior test (locomotion, rearing, total activity) in 2-month-old mice revealed a significant higher activity in mice exposed to repeated doses of 6.6 mg permethrin, as well in mice just receiving a single 6.6 mg dose of permethrin. No significant difference was observed between repeated and single exposure.  A single dose of 0.7 mg bioallethrin on PND 10 caused the same effects as a repeated dose of 0.7 mg between PND 10 to PND 16. This demonstrates that a single dose of these pyrethroids can cause the same developmental neurotoxic effects as that seen following repeated doses over one week during the neonatal BGS period in mouse. This research provides is consistent with previous findings that exposure during the BGS can result in persistent behavioral defects.

  • 35.
    Buratovic, Sonja
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental Toxicology.
    Fredriksson, Anders
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental Toxicology.
    Viberg, Henrik
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental Toxicology.
    Eriksson, Per
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental Toxicology.
    Developmental exposure to PBDE 209 alters adult susceptibility to paraoxon and nicotine: gender and neurobehavioural analysis2011Conference paper (Refereed)
    Abstract [en]

    Newborns, infants and children can be indirectly and directly exposed to PBDEs. This exposure coincides with a period of rapid brain development. Polybrominated diphenyl ethers (PBDEs) are used in large quantities as flame-retardants in polymers, especially in electric appliances.A concern is that these compounds are present at a higher level in newborns and toddlers than in the average adult individual, especially the highly brominated PBDEs. We have earlier reported that neonatal exposure to toxicants can lead to an increased susceptibility of the cholinergic system at adult age. The present study was undertaken to investigate whether neonatal exposure of male and female mice to PBDE 209 alters the adult susceptibility to the organophosphorous compound, paraoxon, and to nicotine, respectively.. Neonatal, 3-day-old, NMRI mice were exposed to PBDE 209 (2,2´,3,3´,4,4´,5,5´,6,6´-decaBDE at 1.4, 6.0 and 14 µmol/kg bw). At two months of age male mice were exposed to paraoxon (0.25 mg/kg bw, every 2nd day for 7 days) and female mice exposed to nicotine. At the age of 2 months male and female mice were observed for spontaneous behaviour in a novel home environment, before and after adult exposure to paraoxon and nicotine, respectively. Adult male and female mice neonatally exposed to PBDE 209 showed significant impaired spontaneous behaviour. Male mice neonatally exposed to PBDE 209 and to paraoxon as adults developed additional defect spontaneous behaviour and lack of habituation. Female mice neonatally exposed to PBDE 209 showed an increased susceptibility to nicotine, where PBDE 209 exposed mice responded with a decrease in activity to nicotine whereas control mice responded with increased activity. The present study shows that PBDE 209 can induce developmental neurobehavioural defects in both male and female mice. Neonatal exposure to PBDE 209 caused also increased susceptibility in adult mice to paraoxon and nicotine. All these effects were dose response related.

  • 36.
    Buratovic, Sonja
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
    Stenerlöw, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Fredriksson, Anders
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
    Sundell-Bergman, Synnöve
    Department of Soil and Environment, Swedish University of Agricultural Sciences, Uppsala, Sweden.
    Eriksson, Per
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
    Developmental effects of fractionated low-dose exposure to gamma radiation on behaviour and susceptibility of the cholinergic system in mice2016In: International Journal of Radiation Biology, ISSN 0955-3002, E-ISSN 1362-3095, Vol. 92, no 7, p. 371-379Article in journal (Refereed)
    Abstract [en]

    Purpose: To investigate whether neonatal exposure to fractionated external gamma radiation and co-exposure to radiation and nicotine can affect/exacerbate developmental neurotoxic effects, including altered behavior/cognitive function and the susceptibility of the cholinergic system in adult male mice. Materials and methods: Neonatal male Naval Medical Research Institute (NMRI) mice were irradiated with one 200 mGy fraction/day and/or exposed to nicotine (66 μg/kg b.w.) twice daily on postnatal day (PND) 10, 10–11, 10–12 or 10–13 (nicotine only). At 2 months of age the animals were tested for spontaneous behavior in a novel home environment, habituation capacity and nicotine-induced behavior. Results: Fractionated irradiation and co-exposure to radiation and nicotine on three consecutive days disrupted behavior and habituation and altered susceptibility of the cholinergic system. All observed effects were significantly more pronounced in mice co-exposed to both radiation and nicotine. Conclusions: The fractionated irradiation regime affects behavior/cognitive function in a similar manner as has previously been observed for single-dose exposures. Neonatal co-exposure to radiation and nicotine, during a critical period of brain development in general and cholinergic system development in particular, enhance these behavioral defects suggesting that the cholinergic system can be a target system for this type of developmental neurotoxic effects.

  • 37.
    Buratovic, Sonja
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
    Stenerlöw, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Fredriksson, Anders
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
    Sundell-Bergman, Synnöve
    Eriksson, Per
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
    Developmental effects of neonatal fractionated co-exposure to low-dose gamma radiation and paraquat on behaviour in adult miceManuscript (preprint) (Other academic)
  • 38.
    Buratovic, Sonja
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental Toxicology.
    Stenerlöw, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Radiology, Oncology and Radiation Science, Biomedical Radiation Sciences.
    Sundell-Bergman, Synnöve
    Sveriges lantbruksuniversitet, Fakulteten för naturresurser och lantbruksvetenskap, Institutionen för Mark och miljö.
    Fredriksson, Anders
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental Toxicology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Psychiatry, University Hospital.
    Eriksson, Per
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental Toxicology.
    Exposure to a single dose of ionising radiation during brain development can cause cognitive defects and increased levels of tau in mice2012Conference paper (Refereed)
    Abstract [en]

    Ionising radiation (IR) is widely used in the medical field for treating tumours, including tumours in the central nervous system, and for imaging techniques such as computed tomography (CT). There is a lack of knowledge and increasing concern about effects and consequences from low dose exposure during critical phases of perinatal and/or neonatal brain development compared to prenatal irradiation. It is known that IR causes neurotoxicological and neurobehavioural defects in mammals. Further, an epidemiological study has suggested that low doses of IR to the human brain during infancy can have a negative effect on cognitive abilities in adulthood. The rapid brain growth spurt (BGS) occurs in humans as well as mice. In humans the BGS starts during the third trimester of pregnancy and continues throughout the first two years of life. In mouse and rat the BGS is neonatal, spanning the first 3-4 weeks of life. The BGS is characterized by maturation of axonal and dendritic outgrowth, establishment of neural connections and acquisition of many new motor and sensory abilities. By using the neonatal mouse as an animal model we are able to study the effect of IR during early periods of brain development and which consequences it has for the adult animal. Disturbances in development caused by nicotine, MeHg, PCBs and PBDEs have previously been shown to alter adult spontaneous behaviour and/or neuroprotein levels in mice.

    Neonatal NMRI male mice were irradiated (0; 0.35 and 0.5 Gy) at one single occasion on postnatal day 10. Mice serving as controls were placed in plastic dishes for a time-period corresponding to the irradiation. Spontaneous behaviour was tested in a novel home environment at 2- and 4-months of age and parameters observed were locomotion, rearing and total activity. Analyses of important neuroprotein levels were performed on 6-month-old control and 0.5 Gy irradiated mice.

    Spontaneous behaviour test (locomotion, rearing, total activity revealed a significantly deranged behaviour in 2- and 4-month old mice irradiated with 0.35 or 0.5 Gy in a dose-response related manner, when compared to controls. The behavioural alterations were manifested as a reduced activity during at the beginning of the observational period and a higher activity at the end of the observational period. Analyses of the neuroprotein tau, which in human medicine is used as a biomarker for Alzheimer’s disease, showed a significantly higher level in mice irradiated with 0.5 Gy compared to controls. This demonstrates that a single dose of gamma radiation, given at a defined critical time period during brain development, is sufficient to cause persistently reduced cognitive functions and increased levels of tau in mice.   

  • 39.
    Buratovic, Sonja
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
    Stenerlöw, Bo
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Sundell-Bergman, Synnöve
    Fredriksson, Anders
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
    Viberg, Henrik
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology.
    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 Organismal Biology, Environmental toxicology.
    Ketamine interacts with low dose ionizing radiaiton during brain development to impair cognitive function in mouse2016In: Anesthesiology, ISSN 0003-3022, E-ISSN 1528-1175Article in journal (Refereed)
  • 40.
    Buratovic, Sonja
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental Toxicology.
    Viberg, Henrik
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental Toxicology.
    Fredriksson, Anders
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental Toxicology.
    Eriksson, Per
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental Toxicology.
    Developmental exposure to PBDE 209: sex, neuroprotein and neurobehavioural analyses2012In: Toxicology Letters, ISSN 0378-4274, E-ISSN 1879-3169, Vol. 211, no supplement, p. S90-Article in journal (Refereed)
    Abstract [en]

    Polybrominated diphenyl ethers (PBDEs) are used in large quantities as flame-retardants in polymers products.Newborns and toddlers can be indirectly and directly exposed to PBDEs during a period of critical rapid brain development. The present study was undertaken to investigate neurotoxic effects after neonatal exposure to PBDE 209 on sex differences, cognitive function, neuroproteins and altered susceptibility to toxicants in adults.

     

    3-day-old NMRI mice were exposed to PBDE 209 (2,2´,3,3´,4,4´,5,5´,6,6´-decaBDE at 0, 1.4, 6.0 and 14 µmol/kg bw). At 2 months of age male mice were exposed to paraoxon (0.25 mg/kg bw, every 2nd day for 7 days) and female mice exposed to nicotine (80 µg nicotine base/kg bw). At the age of 2 and 4 months mice were observed for spontaneous behaviour, before and after adult exposure to paraoxon (male) and nicotine (female). Male mice aged 5 and 7 months were observed for memory and learning. Neuroproteins CaMKII, GAP-43, synaptophysin and tau in cerebral cortex and hippocampus from 7-months old male and female mice were analyzed.

     

    The present study shows that neonatal exposure to PBDE 209 can induce developmental neurobehavioural defects in both male and female mice. Neonatal exposure to PBDE 209 also caused increased susceptibility in adult mice to paraoxon and nicotine. All these effects were dose response related. Further, neonatal exposure to PBDE 209 caused persistent defects in memory and learning in adult male mice and increased levels of important neuroproteins e.g. tau in adult male and female mice.

  • 41.
    Burraco, Pablo
    et al.
    CSIC, Donana Biol Stn, Dept Wetland Ecol, Ecol Evolut & Dev Grp, E-41092 Seville, Spain..
    Valdes, Ana Elisa
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Physiological Botany. Stockholm Univ, Dept Ecol Environm & Plant Sci, SE-10691 Stockholm, Sweden..
    Johansson, Frank
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics.
    Gomez-Mestre, Ivan
    CSIC, Donana Biol Stn, Dept Wetland Ecol, Ecol Evolut & Dev Grp, E-41092 Seville, Spain..
    Physiological mechanisms of adaptive developmental plasticity in Rana temporaria island populations2017In: BMC Evolutionary Biology, ISSN 1471-2148, E-ISSN 1471-2148, Vol. 17, article id 164Article in journal (Refereed)
    Abstract [en]

    Background: Adaptive plasticity is essential for many species to cope with environmental heterogeneity. In particular, developmental plasticity allows organisms with complex life cycles to adaptively adjust the timing of ontogenetic switch points. Size at and time to metamorphosis are reliable fitness indicators in organisms with complex cycles. The physiological machinery of developmental plasticity commonly involves the activation of alternative neuroendocrine pathways, causing metabolic alterations. Nevertheless, we have still incomplete knowledge about how these mechanisms evolve under environments that select for differences in adaptive plasticity. In this study, we investigate the physiological mechanisms underlying divergent degrees of developmental plasticity across Rana temporaria island populations inhabiting different types of pools in northern Sweden. Methods: In a laboratory experiment we estimated developmental plasticity of amphibian larvae from six populations coming from three different island habitats: islands with only permanent pools, islands with only ephemeral pools, and islands with a mixture of both types of pools. We exposed larvae of each population to either constant water level or simulated pool drying, and estimated their physiological responses in terms of corticosterone levels, oxidative stress, and telomere length. Results: We found that populations from islands with only temporary pools had a higher degree of developmental plasticity than those from the other two types of habitats. All populations increased their corticosterone levels to a similar extent when subjected to simulated pool drying, and therefore variation in secretion of this hormone does not explain the observed differences among populations. However, tadpoles from islands with temporary pools showed lower constitutive activities of catalase and glutathione reductase, and also showed overall shorter telomeres. Conclusions: The observed differences are indicative of physiological costs of increased developmental plasticity, suggesting that the potential for plasticity is constrained by its costs. Thus, high levels of responsiveness in the developmental rate of tadpoles have evolved in islands with pools at high but variable risk of desiccation. Moreover, the physiological alterations observed may have important consequences for both short-term odds of survival and long term effects on lifespan.

  • 42.
    Christian, Jan L.
    et al.
    Univ Utah, Sch Med, Div Hematol & Hematol Malignancies, Dept Neurobiol & Anat & Internal Med, Salt Lake City.
    Heldin, Carl-Henrik
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    The TGFβ superfamily in Lisbon: navigating through development and disease2017In: Development, ISSN 0950-1991, E-ISSN 1477-9129, Vol. 144, no 24, p. 4476-4480Article in journal (Other academic)
    Abstract [en]

    The 10th FASEB meeting ‘The TGFβ Superfamily: Signaling in Development and Disease' took place in Lisbon, Portugal, in July 2017. As we review here, the findings presented at the meeting highlighted the important contributions of TGFβ family signaling to normal development, adult homeostasis and disease, and also revealed novel mechanisms by which TGFβ signals are transduced.

  • 43. Clack, J. A.
    et al.
    Ahlberg, Per E.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Evolutionary Organism Biology.
    Finney, S. M.
    Dominguez Alonso, P.
    Robinson, J.
    Ketcham, R. A.
    A uniquely specialized ear in a very early tetrapod2003In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 425, no 6953, p. 66-69Article in journal (Refereed)
  • 44.
    Clement, Alice M.
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Evolution and Developmental Biology. Flinders Univ S Australia, Sch Biol Sci, GPO Box 2100, Adelaide, SA 5001, Australia..
    Long, J. A.
    Flinders Univ S Australia, Sch Biol Sci, GPO Box 2100, Adelaide, SA 5001, Australia..
    Tafforeau, P.
    Flinders Univ S Australia, Sch Biol Sci, GPO Box 2100, Adelaide, SA 5001, Australia.;European Synchrotron Radiat Facil, 71 Ave Martyrs, F-38043 Grenoble, France..
    Ahlberg, Per E.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Evolution and Developmental Biology. Flinders Univ S Australia, Sch Biol Sci, GPO Box 2100, Adelaide, SA 5001, Australia..
    The dipnoan buccal pump reconstructed in 3D and implications for air breathing in Devonian lungfishes2016In: Paleobiology, ISSN 0094-8373, E-ISSN 1938-5331, Vol. 42, no 2, p. 289-304Article in journal (Refereed)
    Abstract [en]

    Lungfishes are known for, and indeed take their name from, their bimodal respiratory abilities. All three extant genera can use their lungs to extract oxygen from the atmosphere, although their reliance upon this capability differs among taxa. Lungs are considered primitive for the Osteichthyes, however the distinctive buccal pump mode of air gulping exhibited by extant lungfishes appears to be a specialization. It is associated with a number of derived skeletal characters (cranial ribs, long parasphenoid stalk, midline gap between palatal tooth plates) that first appeared during the Devonian. These have been described individually, but in no Devonian lungfish has their three-dimensional (3D) spatial relationship been reconstructed and analyzed. Here we present the 3D morphology of Rhinodipterus, a Mid-Late Devonian lungfish from Australia and Europe, based on synchrotron tomography and conventional microtomography scans. Unlike less crownward contemporaneous lungfishes such as Griphognathus and Chirodipterus, Rhinodipterus has a full set of skeletal buccal pump components that can be directly compared to those of extant lungfishes, suggesting that it made more extensive use of air breathing than other Gogo or Bergisch Gladbach genera. This is interesting in relation to the environmental context as Gogo and Bergisch Gladbach are both marine, contrasting with the frequently hypoxic tropical to subtropical fresh water environments inhabited by modern lungfishes. The evolution of buccal pump-supported lung ventilation was evidently not necessarily associated with a transition to non-marine habitats.

  • 45.
    Collet, Julie M.
    et al.
    UCL, Res Dept Genet Evolut & Environm, London, England.;Univ Queensland, Sch Biol Sci, St Lucia, Qld, Australia..
    Fuentes, Sara
    UCL, Res Dept Genet Evolut & Environm, London, England..
    Hesketh, Jack
    UCL, Res Dept Genet Evolut & Environm, London, England..
    Hill, Mark S.
    UCL, Res Dept Genet Evolut & Environm, London, England..
    Innocenti, Paolo
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Animal ecology.
    Morrow, Edward H.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Animal ecology. Univ Sussex, Sch Life Sci, Brighton, E Sussex, England..
    Fowler, Kevin
    UCL, Res Dept Genet Evolut & Environm, London, England..
    Reuter, Max
    UCL, Res Dept Genet Evolut & Environm, London, England..
    Rapid evolution of the intersexual genetic correlation for fitness in Drosophila melanogaster2016In: Evolution, ISSN 0014-3820, E-ISSN 1558-5646, Vol. 70, no 4, p. 781-795Article in journal (Refereed)
    Abstract [en]

    Sexual antagonism (SA) arises when male and female phenotypes are under opposing selection, yet genetically correlated. Until resolved, antagonism limits evolution toward optimal sex-specific phenotypes. Despite its importance for sex-specific adaptation and existing theory, the dynamics of SA resolution are not well understood empirically. Here, we present data from Drosophila melanogaster, compatible with a resolution of SA. We compared two independent replicates of the LHM population in which SA had previously been described. Both had been maintained under identical, controlled conditions, and separated for around 200 generations. Although heritabilities of male and female fitness were similar, the intersexual genetic correlation differed significantly, being negative in one replicate (indicating SA) but close to zero in the other. Using population sequencing, we show that phenotypic differences were associated with population divergence in allele frequencies at nonrandom loci across the genome. Large frequency changes were more prevalent in the population without SA and were enriched at loci mapping to genes previously shown to have sexually antagonistic relationships between expression and fitness. Our data suggest that rapid evolution toward SA resolution has occurred in one of the populations and open avenues toward studying the genetics of SA and its resolution.

  • 46. Constância, Miguel
    et al.
    Hemberger, Myriam
    Hughes, Jennifer
    Dean, Wendy
    Ferguson-Smith, Anne
    Fundele, Reinald
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Animal Development and Genetics.
    Stewart, Francesca
    Kelsey, Gavin
    Fowden, Abigail
    Sibley, Colin
    Reik, Wolf
    Placental-specific IGF-II is a major modulator of placental and fetal growth2002In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 417, no 6892, p. 945-8Article in journal (Refereed)
  • 47. Cross, JC
    et al.
    Coan, PM
    Fundele, Reinald
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Physiology and Developmental Biology, Animal Development and Genetics.
    Hemberger, M
    Kibschull, M
    Ferguson-Smith, AC
    Genes and development: a workshop report2004In: Placenta Supplement A, Trophoblast Research, ISSN 0143-4004, Vol. 18, p. S39-S41Article in journal (Refereed)
  • 48.
    Dijk, Ben
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Animal ecology.
    Laurila, Anssi
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Animal ecology.
    Orizaola, German
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Animal ecology.
    Johansson, Frank
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Animal ecology.
    Is one defence enough?: Disentangling the relative importance of morphological and behavioural predator-induced defences2016In: Behavioral Ecology and Sociobiology, ISSN 0340-5443, E-ISSN 1432-0762, Vol. 70, no 2, p. 237-246Article in journal (Refereed)
    Abstract [en]

    Many organisms show predator-induced behavioural and morphological phenotypic plasticity. These defence mechanisms are often expressed simultaneously. To estimate the relative importance of these two defences, we conducted a laboratory experiment using tadpoles of the common frog (Rana temporaria) as prey and Aeshna dragonfly larvae as predators. We first raised tadpoles in the presence and absence of caged predators to induce differences in defensive morphology, and then conducted free ranging predator trials in environments that were either with or without the presence of predation cues to induce differences in defensive behaviour. This 2 x 2 design allowed us to separate the effects of inducible morphology from inducible behaviour. Caged predators induced deeper bodies and tailfins and reduced activity levels in tadpoles. The time to first capture was shortest in tadpoles without morphological or behavioural defences. Tadpoles with a behavioural defence had a significantly longer time to first capture. Tadpoles with only antipredator morphology tended to have a longer time to first capture as compared to those without any induced defences. This treatment also had a higher number of injured tadpoles as compared to other treatments, suggesting that inducible morphology facilitates predator escape due to the 'lure effect'. However, tadpoles with both behavioural and morphological defences did not have a longer time to first capture as compared to tadpoles with only morphological or behavioural induced defences. Our results suggest that both behavioural and morphological antipredator responses contribute to reduced capture efficiency by predators, but their simultaneous expression did not have any additive effect to the time of first capture and survival, and that the morphology response is most effective when tadpoles are active.

  • 49.
    Dupret, Vincent
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Evolution and Developmental Biology. Uppsala University, Science for Life Laboratory, SciLifeLab. Australian Natl Univ, Dept Appl Math, Res Sch Phys & Engn, Canberra, ACT, Australia..
    Sanchez, Sophie
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Evolution and Developmental Biology. Uppsala University, Science for Life Laboratory, SciLifeLab. European Synchrotron Radiat Facil, Grenoble, France..
    Goujet, Daniel
    UPMC Paris 6, CNRS, MNHN, CR2P UMR 7207,Sorbonne Univ,Museum Natl Hist Nat, Paris, France..
    Ahlberg, Per Erik
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Evolution and Developmental Biology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    The internal cranial anatomy of Romundina stellina Orvig, 1975 (Vertebrata, Placodermi, Acanthothoraci) and the origin of jawed vertebrates: Anatomical atlas of a primitive gnathostome2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 2, article id e0171241Article in journal (Refereed)
    Abstract [en]

    Placoderms are considered as the first jawed vertebrates and constitute a paraphyletic group in the stem-gnathostome grade. The acanthothoracid placoderms are among the phylogenetically most basal and morphologically primitive gnathostomes, but their neurocranial anatomy is poorly understood. Here we present a near-complete three-dimensional skull of Romundina stellina, a small Early Devonian acanthothoracid from the Canadian Arctic Archipelago, scanned with propagation phase contrast microtomography at a 7.46 mu m isotropic voxel size at the European Synchrotron Radiation Facility, Grenoble, France. This is the first model of an early gnathostome skull produced using this technique, and as such represents a major advance in objectivity compared to past descriptions of placoderm neurocrania on the basis of grinding series. Despite some loss of material along an oblique crack, most of the internal structures are remarkably preserved, and most of the missing structures can be reconstructed by symmetry. This virtual approach offers the possibility to connect with certainty all the external foramina to the blood and nerve canals and the central structures, and thus identify accurate homologies without destroying the specimen. The high level of detail enables description of the main arterial, venous and nerve canals of the skull, and other perichondrally ossified endocranial structures such as the palatoquadrate articulations, the endocranial cavity and the inner ear cavities. The braincase morphology appears less extreme than that of Brindabellaspis, and is in some respects more reminiscent of a basal arthrodire such as Kujdanowiaspis.

  • 50.
    Dupré, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Evolutionary Biology.
    Regional and local variation in plant species richness2001Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    In this thesis, I examine the variation in plant species richness along gradients of productivity and disturbance in grasslands and forest habitats in southern Sweden, and I compare the documented patterns with theoretical predictions. Moreover, I evaluate the relative importance of habitat quality and habitat configuration for the occurrence of field layer species in deciduous forests. Finally, I present a new method for the determination of the regional species pool. To examine regional and local variation in plant species richness, I gathered data on species composition in plots of different size (0.001 - 1000 m2) in three vegetation types (deciduous forests, dry grasslands and coastal meadows) in four regions of southern Sweden (Öland, Gotland, Småland and Uppland).

    As predicted by the species pool hypothesis, differences in small-scale species richness of deciduous forests and dry grasslands were correlated with differences in the size of the regional species pool. Moreover, among plots large-scale diversity was predictive of small-scale diversity.

    Species diversity showed a hump-shaped relationship with productivity in forests, and was related to environmental heterogeneity and the size of the 'habitat-specific' species pool. In the two types of grassland examined, grazed sites were richer in species than abandoned sites. Moreover, both species composition and the representation of plants with different life-history characteristics differed between grazed and abandoned sites. As predicted by the intermediate disturbance hypothesis, species richness was highest at intermediate levels of grazing in coastal meadows. However, all the above patterns were scale-dependent, and not observed at all plot sizes.

    The occurrence of field layer species in deciduous forests was more strongly related to habitat quality (mainly soil factors) than to habitat configuration (forest area and isolation). Across species, low seed production, clonal reproduction and habitat specificity were negatively associated with isolation.

12345 1 - 50 of 233
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