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  • 101. Achatz, Johannes Georg
    et al.
    Hooge, Matthew
    Wallberg, Andreas
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Evolution, Genomics and Systematics, Systematic Biology.
    Jondelius, Ulf
    Tyler, Seth
    Systematic revision of acoels with 9+0 sperm ultrastructure (Convolutida) and the influence of sexual conflict on morphology2010In: Journal of Zoological Systematics and Evolutionary Research, ISSN 0947-5745, E-ISSN 1439-0469, Vol. 48, no 1, p. 9-32Article, review/survey (Refereed)
    Abstract [en]

    We have used newly discerned morphological characters as well as molecular-sequence data from 18S and 28S rDNA to revise the families recently designated as the '9+0' acoels - what we call Convolutida. Characters from the ultrastructure of sperm, with their '9+0' axonemes, are useful in delineating the Convolutida, but are either species-specific or too conserved within the group to be used to infer relationships within it. Male genital organs, prostatoid organs, and sagittocysts, on the other hand, give a good phylogenetic signal for reconstructing relationships of such genera as Conaperta, Anaperus, and Achoerus; some features of the reproductive organs correlate with habitat and show how the Convolutida probably originated as epiphytic predators and radiated into the mesopsammon, pelagic, and coral-associated realms. In this revision of the Convolutida we provide revised synopses of its families - which we restrict to the Anaperidae, Convolutidae, and Sagittiferidae - and describe a new species, Polychoerus gordoni, from New Zealand. We transfer the genus Adenopea from the Antroposthiidae to the Convolutidae; Conaperta, Neochildia, and Oxyposthia from the Convolutidae to the Anaperidae; Paranaperus and Praeanaperus from the Anaperidae to the Haploposthiidae. Convoluta aegyptica is synonymized with Convoluta boehmigi, Convoluta lacazii with Convoluta sordida, and the genus Picola (Convolutidae) with Deuterogonaria (Haploposthiidae). Amphiscolops blumi, A. carvalhoi, and A. langerhansi, all of which possess a cellular seminal bursa, are transferred to the genus Heterochaerus. Convoluta elegans and Pseudanaperus tinctus are classified as nomina nuda. We use our findings on the ultrastructure of female genital organs and spermatozoa to show that sexual conflict plays a major role in the evolution of diversity of these structures and that the phylogeny of the Acoela would comprise early forms without female genital organs and hyper- or hypodermal transfer of sperm through advanced forms with ever longer and narrower bursal nozzles and sperm with axial microtubules. Moreover, our results show that the acquisition of endosymbiotic algae happened at least twice within the Acoela.

  • 102. Acheva, Anna
    et al.
    Haghdoost, Siamak
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. University of Caen Normandy, France.
    Sollazzo, Alice
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Launonen, Virpi
    Kamarainen, Meerit
    Presence of Stromal Cells Enhances Epithelial-to-Mesenchymal Transition (EMT) Induction in Lung Bronchial Epithelium after Protracted Exposure to Oxidative Stress of Gamma Radiation2019In: Oxidative Medicine and Cellular Longevity, ISSN 1942-0900, E-ISSN 1942-0994, Vol. 2019, article id 4120379Article in journal (Refereed)
    Abstract [en]

    The aim of the study was to investigate the role of a microenvironment in the induction of epithelial-to-mesenchymal transition (EMT) as a sign of early stages of carcinogenesis in human lung epithelial cell lines after protracted low-dose rate gamma-radiation exposures. BEAS-2B and HBEC-3KT lung cell lines were irradiated with low-dose rate gamma-rays (Cs-137, 1.4 or 14 mGy/h) to 0.1 or 1 Gy with or without adding TGF-beta. TGF-beta-treated samples were applied as positive EMT controls and tested in parallel to find out if the radiation has a potentiating effect on the EMT induction. To evaluate the effect of the stromal component, the epithelial cells were irradiated in cocultures with stromal MRC-9 lung fibroblasts. On day 3 post treatment, the EMT markers: alpha-SMA, vimentin, fibronectin, and E-cadherin, were analyzed. The oxidative stress levels were evaluated by 8-oxo-dG analysis in both epithelial and fibroblast cells. The protracted exposure to low Linear Energy Transfer (LET) radiation at the total absorbed dose of 1 Gy was able to induce changes suggestive of EMT. The results show that the presence of the stromal component and its signaling (TGF-beta) in the cocultures enhances the EMT. Radiation had a minor cumulative effect on the TGF-beta-induced EMT with both doses. The oxidative stress levels were higher than the background in both epithelial and stromal cells post chronic irradiation (0.1 and 1 Gy); as for the BEAS-2B cell line, the increase was statistically significant. We suggest that the induction of EMT in bronchial epithelial cells by radiation requires more than single acute exposure and the presence of stromal component might enhance the effect through free radical production and accumulation.

  • 103. Achidi, E. A.
    et al.
    Apinjoh, T. O.
    Mbunwe, E.
    Besingi, R.
    Yafi, C.
    Awah, N. Wenjighe
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Ajua, A.
    Anchang, J. K.
    Febrile status, malarial parasitaemia and gastro-intestinal helminthiases in schoolchildren resident at different altitudes, in south-western Cameroon2008In: Annals of Tropical Medicine and Parasitology, ISSN 0003-4983, E-ISSN 1364-8594, Vol. 102, no 2, p. 103-118Article in journal (Refereed)
    Abstract [en]

    In the many areas where human malaria and helminthiases are co-endemic, schoolchildren often harbour the heaviest infections and suffer much of the associated morbidity, especially when co-infected. In one such area, the Buea district, in south-western Cameroon, two cross-sectional surveys, together covering 263 apparently healthy schoolchildren aged 4-12 years, were recently conducted. The prevalences of fever, malarial parasitaemia and intestinal helminth infections, the seroprevalences of anti-Plasmodium falciparum IgG and IgE and anti-glycosylphosphatidylinositol (anti-GPI) IgG, plasma concentrations of total IgE, and the incidence of anaemia were all investigated. The mean (S.D.) age of the study children was 7.56 (1.82) years. Overall, 156 (59.3%) of the children were found parasitaemic, with a geometric mean parasitaemia of 565 parasites/mu l. Parasitaemia and fever were significantly associated (P=0.042). The children who lived at low altitude, attending schools that lay 400-650 m above sea level, had significantly higher parasitaemias than their high-altitude counterparts (P < 0.01). At low altitude, the children attending government schools had significantly higher parasitaemias than their mission-school counterparts (P=0.010). Of the 31 children (11.9%) found anaemic, 22 (70.4%) had mild anaemia and none had severe anaemia. A significant negative correlation (r=-0.224; P=0.005) was observed between haemoglobin concentration and level of parasitaemia. Infection with Plasmodium appeared to reduce erythrocyte counts (P=0.045), a condition that was exacerbated by co-infection with helminths (P=0.035). Plasma concentrations of total IgE were higher in the children found to be excreting helminth eggs than in those who appeared helminth-free, while levels of anti-P. falciparum IgE were higher in the children with low-grade parasitaemias than in those with more intense parasitaemias. Levels of anti-GPI IgG increased with age and were relatively high in the children who lived at low altitude and in those who were aparasitaemic. The survey results confirm that asymptomatic malarial parasitaemia frequently co-exists with helminth infections in schoolchildren and indicate links with fever, altitude and school type. Immunoglobulin E may play a role in immune protection against helminthiasis whereas anti-GPI antibodies may be important in the development of antimalarial immunity in such children. In Cameroon, as in other areas with endemic malaria, control programmes to reduce the prevalences of infections with intestinal helminths and malarial parasites in schoolchildren, which may effectively reduce the incidence of anaemia, are clearly needed.

  • 104. Achouiti, Ahmed
    et al.
    Vogl, Thomas
    Urban, Constantin F
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology. Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Röhm, Marc
    Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Clinical Bacteriology.
    Hommes, Tijmen J
    van Zoelen, Marieke AD
    Florquin, Sandrine
    Roth, Johannes
    van't Veer, Cornelis
    de Vos, Alex F
    van der Poll, Tom
    Myeloid-related protein-14 contributes to protective immunity in gram-negative pneumonia derived sepsis2012In: PLoS Pathogens, ISSN 1553-7374, Vol. 8, no 10, p. e1002987-Article in journal (Refereed)
    Abstract [en]

    Klebsiella (K.) pneumoniae is a common cause of pneumonia-derived sepsis. Myeloid related protein 8 (MRP8, S100A8) and MRP14 (S100A9) are the most abundant cytoplasmic proteins in neutrophils. They can form MRP8/14 heterodimers that are released upon cell stress stimuli. MRP8/14 reportedly exerts antimicrobial activity, but in acute fulminant sepsis models MRP8/14 has been found to contribute to organ damage and death. We here determined the role of MRP8/14 in K. pneumoniae sepsis originating from the lungs, using an established model characterized by gradual growth of bacteria with subsequent dissemination. Infection resulted in gradually increasing MRP8/14 levels in lungs and plasma. Mrp14 deficient (mrp14(-/-)) mice, unable to form MRP8/14 heterodimers, showed enhanced bacterial dissemination accompanied by increased organ damage and a reduced survival. Mrp14(-/-) macrophages were reduced in their capacity to phagocytose Klebsiella. In addition, recombinant MRP8/14 heterodimers, but not MRP8 or MRP14 alone, prevented growth of Klebsiella in vitro through chelation of divalent cations. Neutrophil extracellular traps (NETs) prepared from wildtype but not from mrp14(-/-) neutrophils inhibited Klebsiella growth; in accordance, the capacity of human NETs to kill Klebsiella was strongly impaired by an anti-MRP14 antibody or the addition of zinc. These results identify MRP8/14 as key player in protective innate immunity during Klebsiella pneumonia.

  • 105.
    Ackefors, Hans
    Stockholm University, Faculty of Science, Department of Zoology, Animal Ecology.
    Global fisheries - threats and opportunities2009In: Fisheries, sustainablity and development: fifty-two authors on coexistence and development of fisheries and aquaculture in developing and developed countries / [ed] Per Wramner, Hans Ackefors et al, Stockholm: Kungl. Skogs- och lantbruksakademien , 2009, p. 35-68-Chapter in book (Other academic)
  • 106.
    Ackefors, Hans
    Stockholm University.
    Studies on the ecology of the zooplankton fauna in the Baltic proper1971Doctoral thesis, comprehensive summary (Other academic)
  • 107.
    Ackefors, Hans
    Stockholm University, Faculty of Science, Department of Zoology, Animal Ecology.
    The evolution of a worldwide shrimp industry2009In: World Aquaculture, ISSN 1041-5602, Vol. 40, no 3, p. 46-55Article in journal (Refereed)
  • 108.
    Ackefors, Hans
    Stockholm University, Faculty of Science, Department of Zoology, Animal Ecology.
    Är det politikerna eller fiskenäringen som styr fisket?2008In: Kungl. Skogs- och Lantbruksakademiens Tidskrift, ISSN 0023-5350, Vol. 147, no 2, p. 36-43Article in journal (Other (popular science, discussion, etc.))
  • 109.
    Acuna, Lillian G.
    et al.
    Fundación Ciencia & Vida, Chile ; Universidad Andres Bello, Chile.
    Pablo Cardenas, Juan
    Fundación Ciencia & Vida, Chile ; Universidad Andres Bello, Chile.
    Covarrubias, Paulo C.
    Fundación Ciencia & Vida, Chile ; Universidad Andres Bello, Chile.
    Jose Haristoy, Juan
    Fundación Ciencia & Vida, Chile.
    Flores, Rodrigo
    Fundación Ciencia & Vida, Chile.
    Nuñez, Harold
    Fundación Ciencia & Vida, Chile.
    Riadi, Gonzalo
    Universidad de Talca, Chile.
    Shmaryahu, Amir
    Fundación Ciencia & Vida, Chile.
    Valdes, Jorge
    Center for Systems Biotechnology, Chile.
    Dopson, Mark
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science.
    Rawlings, Douglas E.
    University of Stellenbosch, South Africa.
    Banfield, Jillian F.
    University of California, USA.
    Holmes, David S.
    Fundación Ciencia & Vida, Chile ; Universidad Andres Bello, Chile.
    Quatrini, Raquel
    Fundación Ciencia & Vida, Chile ; Universidad Andres Bello, Chile.
    Architecture and Gene Repertoire of the Flexible Genome of the Extreme Acidophile Acidithiobacillus caldus2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 11, article id e78237Article in journal (Refereed)
    Abstract [en]

    Background: Acidithiobacillus caldus is a sulfur oxidizing extreme acidophile and the only known mesothermophile within the Acidithiobacillales. As such, it is one of the preferred microbes for mineral bioprocessing at moderately high temperatures. In this study, we explore the genomic diversity of A. caldus strains using a combination of bioinformatic and experimental techniques, thus contributing first insights into the elucidation of the species pangenome. Principal Findings: Comparative sequence analysis of A. caldus ATCC 51756 and SM-1 indicate that, despite sharing a conserved and highly syntenic genomic core, both strains have unique gene complements encompassing nearly 20% of their respective genomes. The differential gene complement of each strain is distributed between the chromosomal compartment, one megaplasmid and a variable number of smaller plasmids, and is directly associated to a diverse pool of mobile genetic elements (MGE). These include integrative conjugative and mobilizable elements, genomic islands and insertion sequences. Some of the accessory functions associated to these MGEs have been linked previously to the flexible gene pool in microorganisms inhabiting completely different econiches. Yet, others had not been unambiguously mapped to the flexible gene pool prior to this report and clearly reflect strain-specific adaption to local environmental conditions. Significance: For many years, and because of DNA instability at low pH and recurrent failure to genetically transform acidophilic bacteria, gene transfer in acidic environments was considered negligible. Findings presented herein imply that a more or less conserved pool of actively excising MGEs occurs in the A. caldus population and point to a greater frequency of gene exchange in this econiche than previously recognized. Also, the data suggest that these elements endow the species with capacities to withstand the diverse abiotic and biotic stresses of natural environments, in particular those associated with its extreme econiche.

  • 110. Adam, B.
    et al.
    Klawonn, I.
    Svedén, J.
    Bergkvist, J.
    Nahar, N.
    Walve, J.
    Littmann, S.
    Whitehouse, Martin J.
    Swedish Museum of Natural History, Department of Geology.
    Lavik, G.
    Kuypers, M.M.M.
    Ploug, H.
    N2-fixation, ammonium release, and N-transfer to the microbial and classical food web within a plankton community.2016In: The ISME Journal, ISSN 1751-7362, E-ISSN 1751-7370, Vol. 19, p. 450-459Article in journal (Refereed)
    Abstract [en]

    We investigated the role of N2-fixation by the colony-forming cyanobacterium, Aphanizomenon spp., for the plankton community and N-budget of the N-limited Baltic Sea during summer by using stable isotope tracers combined with novel secondary ion mass spectrometry, conventional mass spectrometry and nutrient analysis. When incubated with 15N2, Aphanizomenon spp. showed a strong 15N-enrichment implying substantial 15N2-fixation. Intriguingly, Aphanizomenon did not assimilate tracers of 15NH4+ from the surrounding water. These findings are in line with model calculations that confirmed a negligible N-source by diffusion-limited NH4+ fluxes to Aphanizomenon colonies at low bulk concentrations (<250 nm) as compared with N2-fixation within colonies. No N2-fixation was detected in autotrophic microorganisms <5 μm, which relied on NH4+ uptake from the surrounding water. Aphanizomenon released about 50% of its newly fixed N2 as NH4+. However, NH4+ did not accumulate in the water but was transferred to heterotrophic and autotrophic microorganisms as well as to diatoms (Chaetoceros sp.) and copepods with a turnover time of ~5 h. We provide direct quantitative evidence that colony-forming Aphanizomenon releases about half of its recently fixed N2 as NH4+, which is transferred to the prokaryotic and eukaryotic plankton forming the basis of the food web in the plankton community. Transfer of newly fixed nitrogen to diatoms and copepods furthermore implies a fast export to shallow sediments via fast-sinking fecal pellets and aggregates. Hence, N2-fixing colony-forming cyanobacteria can have profound impact on ecosystem productivity and biogeochemical processes at shorter time scales (hours to days) than previously thought.

  • 111. Adam, Birgit
    et al.
    Klawonn, Isabell
    Stockholm University, Faculty of Science, Department of Ecology, Environment and Plant Sciences.
    Svedén, Jenny B.
    Stockholm University, Faculty of Science, Department of Ecology, Environment and Plant Sciences.
    Bergkvist, Johanna
    Nahar, Nurun
    Walve, Jakob
    Stockholm University, Faculty of Science, Department of Ecology, Environment and Plant Sciences.
    Littmann, Sten
    Whitehouse, Martin J.
    Lavik, Gaute
    Kuypers, Marcel M. M.
    Ploug, Helle
    Stockholm University, Faculty of Science, Department of Ecology, Environment and Plant Sciences. University of Gothenburg, Sweden.
    N2-fixation, ammonium release and N-transfer to the microbial and classical food web within a plankton community2016In: The ISME Journal, ISSN 1751-7362, E-ISSN 1751-7370, Vol. 10, no 2, p. 450-459Article in journal (Refereed)
    Abstract [en]

    We investigated the role of N2-fixation by the colony-forming cyanobacterium, Aphanizomenon spp., for the plankton community and N-budget of the N-limited Baltic Sea during summer by using stable isotope tracers combined with novel secondary ion mass spectrometry, conventional mass spectrometry and nutrient analysis. When incubated with 15N2Aphanizomenon spp. showed a strong 15N-enrichment implying substantial 15N2-fixation. Intriguingly, Aphanizomenon did not assimilate tracers of 15NH4+ from the surrounding water. These findings are in line with model calculations that confirmed a negligible N-source by diffusion-limited NH4+ fluxes to Aphanizomenon colonies at low bulk concentrations (<250 nm) as compared with N2-fixation within colonies. No N2-fixation was detected in autotrophic microorganisms <5 μm, which relied on NH4+uptake from the surrounding water. Aphanizomenon released about 50% of its newly fixed N2 as NH4+. However, NH4+ did not accumulate in the water but was transferred to heterotrophic and autotrophic microorganisms as well as to diatoms (Chaetoceros sp.) and copepods with a turnover time of ~5 h. We provide direct quantitative evidence that colony-formingAphanizomenon releases about half of its recently fixed N2 as NH4+, which is transferred to the prokaryotic and eukaryotic plankton forming the basis of the food web in the plankton community. Transfer of newly fixed nitrogen to diatoms and copepods furthermore implies a fast export to shallow sediments via fast-sinking fecal pellets and aggregates. Hence, N2-fixing colony-forming cyanobacteria can have profound impact on ecosystem productivity and biogeochemical processes at shorter time scales (hours to days) than previously thought.

  • 112. Adamczyk, Bartosz
    et al.
    Sietio, Outi-Maaria
    Strakoya, Petra
    Prommer, Judith
    Wild, Birgit
    Stockholm University, Faculty of Science, Department of Environmental Science and Analytical Chemistry. University of Vienna, Austria; University of Gothenburg, Sweden.
    Hagner, Marleena
    Pihlatie, Mari
    Fritze, Hannu
    Richter, Andreas
    Heinonsalo, Jussi
    Plant roots increase both decomposition and stable organic matter formation in boreal forest soil2019In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 10, article id 3982Article in journal (Refereed)
    Abstract [en]

    Boreal forests are ecosystems with low nitrogen (N) availability that store globally significant amounts of carbon (C), mainly in plant biomass and soil organic matter (SOM). Although crucial for future climate change predictions, the mechanisms controlling boreal C and N pools are not well understood. Here, using a three-year field experiment, we compare SOM decomposition and stabilization in the presence of roots, with exclusion of roots but presence of fungal hyphae and with exclusion of both roots and fungal hyphae. Roots accelerate SOM decomposition compared to the root exclusion treatments, but also promote a different soil N economy with higher concentrations of organic soil N compared to inorganic soil N accompanied with the build-up of stable SOM-N. In contrast, root exclusion leads to an inorganic soil N economy (i.e., high level of inorganic N) with reduced stable SOM-N buildup. Based on our findings, we provide a framework on how plant roots affect SOM decomposition and stabilization.

  • 113.
    Adams, David A.
    et al.
    Department of Biology, Middle Tennessee State University, USA.
    Walck, Jeffery L.
    Department of Biology, Middle Tennessee State University, USA.
    Howard, R. Stephen
    Department of Biology, Middle Tennessee State University, USA.
    Milberg, Per
    Linköping University, Department of Physics, Chemistry and Biology, Ecology. Linköping University, The Institute of Technology.
    Forest Composition and Structure onGlade-forming Limestones in Middle Tennessee2012In: Castanea, ISSN 0008-7475, Vol. 77, no 4, p. 335-347Article in journal (Refereed)
    Abstract [en]

    Within a successional context, the vegetation associated with the cedar gladeecosystem in middle Tennessee develops from bare limestone bedrock to subclimax redcedar,preclimax oak-hickory, and climax mixed hardwood forests. Studies on the composition andstructure of forests associated with cedar glade–forming limestones (Lebanon, Ridley) are rare.We sampled the canopy and understory of six forest stands in middle Tennessee on theselimestones. Observed number of canopy species was 14–24 across stands; estimated richnesswas greater by 1–3 species (bootstrap) or 3–6 species (first-order jackknife) than observedrichness. With the exception of Ailanthus altissima in one stand, all other canopy species werenative. Juniperus virginiana, Fraxinus americana, Carya ovata, and Quercus muehlenbergii wereprimary canopy components in 4 or 6 stands, and C. glabra, Q. shumardii, Ulmus alata, F.quadrangulata, Q. alba, and Q. velutina in 2–3 stands. When we included stands from apreviously published study (most on the non-glade Carters Limestone) with our data, aprincipal components analysis identified three groups with the axes approximating a moisturebedrockgradient and a time-successional gradient. An examination of regeneration in ourstands predicts that (1) mesophytes and/or fire-sensitive species (Acer saccharum, Fraxinus spp.,Celtis spp.) will increase and (2) xerophytes and/or fire-adapted species (Quercus spp., Caryaspp.) will decrease. Altogether, our results strongly suggest that the oak-hickory stage shown insuccessional outlines of vegetation development associated with the cedar glade ecosystem maynot occur in its current state in the future.

  • 114. Adamsson, I
    et al.
    Edlund, Charlotta
    Södertörn University, Avdelning Naturvetenskap.
    Seensalu, R
    Engstrand, L
    The use of AP-PCR and flaA-RFLP typing to investigate treatment failure in Helicobacter pylori infection2000In: Clinical Microbiology and Infection, ISSN 1198-743X, E-ISSN 1469-0691, Vol. 6, no 5, p. 265-267Article in journal (Refereed)
  • 115. Adase, Christopher A.
    et al.
    Draheim, Roger R.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Manson, Michael D.
    The Residue Composition of the Aromatic Anchor of the Second Transmembrane Helix Determines the Signaling Properties of the Aspartate/Maltose Chemoreceptor Tar of Escherichia coli2012In: Biochemistry, ISSN 0006-2960, E-ISSN 1520-4995, Vol. 51, no 9, p. 1925-1932Article in journal (Refereed)
    Abstract [en]

    Repositioning of the tandem aromatic residues (Trp-209 and Tyr-210) at the cytoplasmic end of the second transmembrane helix (TM2) modulates the signal output of the aspartate/maltose chemoreceptor of Escherichia coli (Tar(Ec)). Here, we directly assessed the effect of the residue composition of the aromatic anchor by studying the function of a library of Tar(Ec) variants that possess all possible combinations of Ala, Phe, Tyr, and Trp at positions 209 and 210. We identified three important properties of the aromatic anchor. First, a Trp residue at position 209 was required to maintain clockwise (CW) signal output in the absence of adaptive methylation, but adaptive methylation restored the ability of all of the mutant receptors to generate CW rotation. Second, when the aromatic anchor was replaced with tandem Ala residues, signaling was less compromised than when an Ala residue occupied position 209 and an aromatic residue occupied position 210. Finally, when Trp was: present at position 209, the identity of the residue at position 210 had little effect on baseline signal output or aspartate chemotaxis, although maltose taxis was significantly affected by some substitutions at position 210. All of the mutant receptors we constructed supported some level of aspartate and maltose taxis in semisolid agar swim plates, but those without Trp at position 209 were overmethylated in their baseline signaling state. These results show the importance of the cytoplasmic aromatic anchor of TM2 in maintaining the baseline Tar(Ec) signal output and responsiveness to attractant signaling.

  • 116. Adase, Christopher A.
    et al.
    Draheim, Roger R.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Goethe University .
    Rueda, Garrett
    Desai, Raj
    Manson, Michael D.
    Residues at the Cytoplasmic End of Transmembrane Helix 2 Determine the Signal Output of the Tar(Ec) Chemoreceptor2013In: Biochemistry, ISSN 0006-2960, E-ISSN 1520-4995, Vol. 52, no 16, p. 2729-2738Article in journal (Refereed)
    Abstract [en]

    Baseline signal output and communication between the periplasmic and cytoplasmic domains of the Escherichia colt aspartate chemoreceptor Tar(Ec) are both strongly influenced by residues at the C-terminus of transmembrane helix 2 (TM2). In particular, the cytoplasmic aromatic anchor, composed of residues Trp-209 and Tyr-210 in wild type Tar(Ec) is important for determining the CheA kinase-stimulating activity of the receptor and its ability to respond to chemoeffector-induced stimuli. Here, we have studied the effect on Tar(Ec) function of the six residue sequence at positions 207-212 Moving various combinations of aromatic residues among these positions generates substantial changes M receptor activity. Trp has the largest effect on function, both in maintaining normal activity and in altering activity when it is moved. Tyr has a weaker effect, and Phe has the weakest; however, all three aromatic residues can alter signal output when they are placed in novel positions. We also find that Gly-211 plays an important role in receptor function, perhaps because of the flexibility it introduces into the TM2-HAMP domain connector. The conservation of this Gly residue in the high-abundance chemoreceptors of E. coli and Salmonella enterica suggests that it may be important for the nuanced, bidirectional transmembrane signaling that occurs in these proteins.

  • 117.
    Adhikari, Deepak
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Signaling pathways in the development of female germ cells2014Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Primordial follicles are the first small follicles to appear in the mammalian ovary. Women are born with a fixed number of primordial follicles in the ovaries. Once formed, the pool of primordial follicles serves as a source of developing follicles and oocytes. The first aim of this thesis was to investigate the functional role of the intra-oocyte signaling pathways, especially the phosphatidylinositol-3 kinase (PI3K) and mammalian target of rapamycin complex 1 (mTORC1) pathways in the regulation of primordial follicle activation and survival. We found that a primordial follicle remains dormant when the PI3K and mTORC1 signaling in its oocyte is activated to an appropriate level, which is just sufficient to maintain its survival, but not sufficient for its growth initiation. Hyperactivation of either of these signaling pathways causes global activation of the entire pool of primordial follicles leading to the exhaustion of all the follicles in young adulthood in mice. Mammalian oocytes, while growing within the follicles, remain arrested at prophase I of meiosis. Oocytes within the fully-grown antral follicles resume meiosis upon a preovulatory surge of leutinizing hormone (LH), which indicates that LH mediates the resumption of meiosis. The prophase I arrest in the follicle-enclosed oocyte is the result of low maturation promoting factor (MPF) activity, and resumption of meiosis upon the arrival of hormonal signals is mediated by activation of MPF. MPF is a complex of cyclin dependent kinase 1 (Cdk1) and cyclin B1, which is essential and sufficient for entry into mitosis. Although much of the mitotic cell cycle machinery is shared during meiosis, lack of Cdk2  in mice leads to a postnatal loss of all oocytes, indicating that Cdk2 is important for oocyte survival, and probably oocyte meiosis also. There have been conflicting results earlier about the role of Cdk2 in metaphase II arrest of Xenopus  oocytes. Thus the second aim of the thesis was to identify the specific Cdk that is essential for mouse oocyte meiotic maturation. We generated mouse models with oocytespecific deletion of Cdk1  or Cdk2  and studied the specific requirements of Cdk1 and Cdk2 during resumption of oocyte meiosis. We found that only Cdk1 is essential and sufficient for the oocyte meiotic maturation. Cdk1 does not only phosphorylate the meiotic phosphoproteins during meiosis resumption but also phosphorylates and suppresses the downstream protein phosphatase 1, which is essential for protecting the Cdk1 substrates from dephosphorylation.

  • 118.
    Adhikari, Deepak
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Flohr, Gilian
    Hogeschool Leiden, Zernikedreef 11,2333 CK Leiden, The Netherlands.
    Gorre, Nagaraju
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Shen, Yan
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Yang, Hairu
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Lan, Zijian
    University of Louisville Health Sciences Center, Louisville, Kentucky, USA.
    Liu, Kui
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Disruption of Tsc2 in oocytes leads to overactivation of the entire pool of primordial follicles2009In: Molecular human reproduction, ISSN 1360-9947, E-ISSN 1460-2407, Vol. 15, no 12, p. 765-770Article in journal (Refereed)
    Abstract [en]

    To maintain the length of reproductive life in a woman, it is essential that most of her ovarian primordial follicles are maintained in a quiescent state to provide a continuous supply of oocytes. However, our understanding of the molecular mechanisms that control the quiescence and activation of primordial follicles is still in its infancy. In this study, we provide some genetic evidence to show that the tumor suppressor tuberous sclerosis complex 2 (Tsc2), which negatively regulates mammalian target of rapamycin complex 1 (mTORC1), functions in oocytes to maintain the dormancy of primordial follicles. In mutant mice lacking the Tsc2 gene in oocytes, the pool of primordial follicles is activated prematurely due to elevated mTORC1 activity in oocytes. This results in depletion of follicles in early adulthood, causing premature ovarian failure (POF). Our results suggest that the Tsc1-Tsc2 complex mediated suppression of mTORC1 activity is indispensable for maintenance of the dormancy of primordial follicles, thus preserving the follicular pool, and that mTORC1 activity in oocytes promotes follicular activation. Our results also indicate that deregulation of Tsc/mTOR signaling in oocytes may cause pathological conditions of the ovary such as infertility and POF.

  • 119. Adhikari, P. R.
    et al.
    Upadhyaya, B. B.
    Meng, Chen
    KTH, School of Computer Science and Communication (CSC), Computational Biology, CB.
    Hollmén, J.
    Gene selection in time-series gene expression data2011In: 6th IAPR International Conference on Pattern Recognition in Bioinformatics, PRIB 2011, 2011, p. 145-156Conference paper (Refereed)
    Abstract [en]

    The dimensionality of biological data is often very high. Feature selection can be used to tackle the problem of high dimensionality. However, majority of the work in feature selection consists of supervised feature selection methods which require class labels. The problem further escalates when the data is time-series gene expression measurements that measure the effect of external stimuli on biological system. In this paper we propose an unsupervised method for gene selection from time-series gene expression data founded on statistical significance testing and swap randomization. We perform experiments with a publicly available mouse gene expression dataset and also a human gene expression dataset describing the exposure to asbestos. The results in both datasets show a considerable decrease in number of genes.

  • 120.
    Adl, Sina M.
    et al.
    Univ Saskatchewan, Dept Soil Sci, Coll Agr & Bioresources, 51 Campus Dr, Saskatoon, SK S7N 5A8, Canada.
    Bass, David
    Nat Hist Museum, Dept Life Sci, Cromwell Rd, London SW7 5BD, England;CEFAS, Barrack Rd, Weymouth DT4 8UB, Dorset, England.
    Lane, Christopher E.
    Univ Rhode Isl, Dept Biol Sci, Kingston, RI 02881 USA.
    Lukes, Julius
    Czech Acad Sci, Biol Ctr, Inst Parasitol, Ceske Budejovice 37005, Czech Republic;Univ South Bohemia, Fac Sci, Ceske Budejovice 37005, Czech Republic.
    Schoch, Conrad L.
    Natl Inst Biotechnol Informat, Natl Lib Med, NIH, Bethesda, MD 20892 USA.
    Smirnov, Alexey
    St Petersburg State Univ, Fac Biol, Dept Invertebrate Zool, St Petersburg 199034, Russia.
    Agatha, Sabine
    Univ Salzburg, Dept Biosci, Hellbrunnerstr 34, A-5020 Salzburg, Austria.
    Berney, Cedric
    CNRS, UMR 7144 AD2M, Grp Evolut Protistes & Ecosyst Pelag, Stn Biol Roscoff, Pl Georges Teissier, F-29680 Roscoff, France.
    Brown, Matthew W.
    Mississippi State Univ, Dept Biol Sci, Starkville, MS 39762 USA;Mississippi State Univ, Inst Genom Biocomp & Biotechnol, Starkville, MS 39762 USA.
    Burki, Fabien
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Systematic Biology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Cárdenas, Paco
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Farmakognosi.
    Cepicka, Ivan
    Charles Univ Prague, Dept Zool, Fac Sci, Vinicna 7, CR-12844 Prague, Czech Republic.
    Chistyakova, Lyudmila
    St Petersburg State Univ, Core Facil Ctr Culture Collect Microorganisms, St Petersburg 198504, Russia.
    del Campo, Javier
    CSIC, Inst Ciencies Mar, Passeig Maritim Barceloneta 37-49, E-08003 Barcelona, Catalonia, Spain.
    Dunthorn, Micah
    Univ Kaiserslautern, Dept Ecol, Erwin Schroedinger St, D-67663 Kaiserslautern, Germany;Univ Duisburg Essen, Dept Eukaryot Microbiol, Univ Str 5, D-45141 Essen, Germany.
    Edvardsen, Bente
    Univ Oslo, Dept Biosci, POB 1066 Blindern, N-0316 Oslo, Norway.
    Eglit, Yana
    Dalhousie Univ, Dept Biol, Halifax B3H 4R2, NS, Canada.
    Guillou, Laure
    Univ Paris 06, Sorbonne Univ, Paris 6, CNRS,UMR 7144 AD2M,Stn Biol Roscoff, Pl Georges Teissier,,CS90074, F-29688 Roscoff, France.
    Hampl, Vladimir
    Charles Univ Prague, Dept Parasitol, Fac Sci, BIOCEV, Prumyslov 595, Vestec 25242, Czech Republic.
    Heiss, Aaron A.
    Amer Museum Nat Hist, Dept Invertebrate Zool, New York, NY 10024 USA.
    Hoppenrath, Mona
    DZMB German Ctr Marine Biodivers Res, D-26382 Wilhelmshaven, Germany.
    James, Timothy Y.
    Univ Michigan, Dept Ecol & Evolutionary Biol, Ann Arbor, MI 48109 USA.
    Karnkowska, Anna
    Univ Warsaw, Dept Mol Phylogenet & Evolut, PL-02089 Warsaw, Poland.
    Karpov, Sergey
    St Petersburg State Univ, Fac Biol, Dept Invertebrate Zool, St Petersburg 199034, Russia;RAS, Lab Parasit Worms & Protistol, Zool Inst, St Petersburg 199034, Russia.
    Kim, Eunsoo
    Amer Museum Nat Hist, Dept Invertebrate Zool, New York, NY 10024 USA.
    Kolisko, Martin
    Czech Acad Sci, Biol Ctr, Inst Parasitol, Ceske Budejovice 37005, Czech Republic.
    Kudryavtsev, Alexander
    St Petersburg State Univ, Fac Biol, Dept Invertebrate Zool, St Petersburg 199034, Russia;RAS, Lab Parasit Worms & Protistol, Zool Inst, St Petersburg 199034, Russia.
    Lahr, Daniel J. G.
    Univ Sao Paulo, Dept Zool, Inst Biosci, Matao Travessa 14 Cidade Univ, BR-05508090 Sao Paulo, SP, Brazil.
    Lara, Enrique
    Univ Neuchatel, Lab Soil Biodivers, Rue Emile Argand 11, CH-2000 Neuchatel, Switzerland;CSIC, Real Jardim Bot,Plaza Murillo 2, E-28014 Madrid, Spain.
    Le Gall, Line
    Sorbonne Univ, Museum Natl Hist Nat, Inst Systemat Evolut Biodiversit, 57 Rue Cuvier,CP 39, F-75005 Paris, France.
    Lynn, Denis H.
    Univ Guelph, Dept Integrat Biol, Summerlee Sci Complex, Guelph, ON N1G 2W1, Canada;Univ British Columbia, Dept Zool, 4200-6270 Univ Blvd, Vancouver, BC V6T 1Z4, Canada.
    Mann, David G.
    Royal Bot Garden, Edinburgh EH3 5LR, Midlothian, Scotland;Inst Agrifood Res & Technol, C Poble Nou Km 5-5, E-43540 San Carlos de la Rapita, Spain.
    Massana, Ramon
    CSIC, Inst Ciencies Mar, Passeig Maritim Barceloneta 37-49, E-08003 Barcelona, Catalonia, Spain.
    Mitchell, Edward A. D.
    Univ Neuchatel, Lab Soil Biodivers, Rue Emile Argand 11, CH-2000 Neuchatel, Switzerland;Jardin Bot Neuchatel,Chemin Perthuis du Salut 58, CH-2000 Neuchatel, Switzerland.
    Morrow, Christine
    Natl Museums Northern Ireland, Dept Nat Sci, 153 Bangor Rd, Holywood BT18 0EU, England.
    Park, Jong Soo
    Kyungpook Natl Univ, Sch Earth Syst Sci, Dept Oceanog, Daegu, South Korea;Kyungpook Natl Univ, Sch Earth Syst Sci, Kyungpook Inst Oceanog, Daegu, South Korea.
    Pawlowski, Jan W.
    Univ Geneva, Dept Genet & Evolut, CH-1211 Geneva 4, Switzerland.
    Powell, Martha J.
    Univ Alabama, Dept Biol Sci, Tuscaloosa, AL 35487 USA.
    Richter, Daniel J.
    Univ Pompeu Fabra, CSIC, Inst Biol Evolut, Passeig Maritim Barceloneta 37-49, Barcelona 08003, Spain.
    Rueckert, Sonja
    Edinburgh Napier Univ, Sch Appl Sci, Edinburgh EH11 4BN, Midlothian, Scotland.
    Shadwick, Lora
    Univ Arkansas, Dept Biol Sci, Fayetteville, AR 72701 USA.
    Shimano, Satoshi
    Hosei Univ, Sci Res Ctr, Chiyoda Ku, 2-17-1 Fujimi, Tokyo, Japan.
    Spiegel, Frederick W.
    Univ Arkansas, Dept Biol Sci, Fayetteville, AR 72701 USA.
    Torruella, Guifre
    Univ Paris XI, Lab Evolut & Systemat, F-91405 Orsay, France.
    Youssef, Noha
    Oklahoma State Univ, Dept Microbiol & Mol Genet, Stillwater, OK 74074 USA.
    Zlatogursky, Vasily V.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Systematic Biology. St Petersburg State Univ, Fac Biol, Dept Invertebrate Zool, St Petersburg 199034, Russia.
    Zhang, Qianqian
    Chinese Acad Sci, Yantai Inst Coastal Zone Res, Yantai 264003, Peoples R China.
    Revisions to the Classification, Nomenclature, and Diversity of Eukaryotes2019In: Journal of Eukaryotic Microbiology, ISSN 1066-5234, E-ISSN 1550-7408, Vol. 66, no 1, p. 4-119Article in journal (Refereed)
    Abstract [en]

    This revision of the classification of eukaryotes follows that of Adl et al., 2012 [J. Euk. Microbiol. 59(5)] and retains an emphasis on protists. Changes since have improved the resolution of many nodes in phylogenetic analyses. For some clades even families are being clearly resolved. As we had predicted, environmental sampling in the intervening years has massively increased the genetic information at hand. Consequently, we have discovered novel clades, exciting new genera and uncovered a massive species level diversity beyond the morphological species descriptions. Several clades known from environmental samples only have now found their home. Sampling soils, deeper marine waters and the deep sea will continue to fill us with surprises. The main changes in this revision are the confirmation that eukaryotes form at least two domains, the loss of monophyly in the Excavata, robust support for the Haptista and Cryptista. We provide suggested primer sets for DNA sequences from environmental samples that are effective for each clade. We have provided a guide to trophic functional guilds in an appendix, to facilitate the interpretation of environmental samples, and a standardized taxonomic guide for East Asian users.

  • 121.
    Adler, J
    et al.
    Stockholms universitet, Wenner-Grens institut för experimentell biologi.
    Pagakis, S N
    Parmryd, I
    Stockholms universitet, Wenner-Grens institut för experimentell biologi.
    Replicate-based noise corrected correlation for accurate measurements of colocalization.2008In: Journal of Microscopy, ISSN 0022-2720, E-ISSN 1365-2818, Vol. 230, no Pt 1, p. 121-33Article in journal (Refereed)
  • 122.
    Adler, Jeremy
    et al.
    Stockholms universitet, Wenner-Grens institut för experimentell biologi.
    Parmryd, Ingela
    Stockholms universitet, Wenner-Grens institut för experimentell biologi.
    In support of the Pearson correlation coefficient.2007In: Journal of Microscopy, Vol. 227, no Pt 1, p. 83; author reply 84-5Article in journal (Other academic)
  • 123.
    Adler, Jeremy
    et al.
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Cell Biology.
    Parmryd, Ingela
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Cell Biology.
    Plasma membrane topology and membrane models2009Conference paper (Other academic)
  • 124.
    Adler, Jeremy
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Cancer and Vascular Biology.
    Parmryd, Ingela
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Quantification of Colocalisation; Co-Occurrence, Correlation, Empty Voxels, Regions of Interest and Thresholding2014In: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 106, no 2, p. 602A-602AArticle in journal (Other academic)
    Abstract [en]

    Measuring colocalisation is not straightforward with a plethora of coefficients that encapsulate different definitions. Measurements may also be implemented differently. Not only do measurements differ; interconversion is impossible making comparisons challenging. There is a need to cull coefficients and for clear definitions of what precisely is meant by colocalisation in individual studies. Colocalisation can be considered to have two components; co-occurrence which reports whether the fluorophores are found together and correlation which reports on the similarity in their patterns of intensity.

  • 125.
    Adler, Jeremy
    et al.
    Stockholms universitet, Wenner-Grens institut.
    Parmryd, Ingela
    Stockholms universitet, Wenner-Grens institut.
    Quantifying Colocalization by Correlation: The Pearson Correlation Coefficient is Superior to the Mander's Overlap Coefficient2010In: CYTOMETRY PART A, ISSN 1552-4922, Vol. 77A, no 8, p. 733-742Article in journal (Refereed)
    Abstract [en]

    The Pearson correlation coefficient (PCC) and the Mander's overlap coefficient (MOC) are used to quantify the degree of colocalization between fluorophores. The MOC was introduced to overcome perceived problems with the PCC. The two coefficients are mathematically similar, differing in the use of either the absolute intensities (MOC) or of the deviation from the mean (PCC). A range of correlated datasets, which extend to the limits of the PCC, only evoked a limited response from the MOC. The PCC is unaffected by changes to the offset while the MOC increases when the offset is positive. Both coefficients are independent of gain. The MOC is a confusing hybrid measurement, that combines correlation with a heavily weighted form of co-occurrence, favors high intensity combinations, downplays combinations in which either or both intensities are low and ignores blank pixels. The PCC only measures correlation. A surprising finding was that the addition of a second uncorrelated population can substantially increase the measured correlation, demonstrating the importance of excluding background pixels. Overall, since the MOC is unresponsive to substantial changes in the data and is hard to interpret, it is neither an alternative to nor a useful substitute for the PCC. The MOC is not suitable for making measurements of colocalization either by correlation or co-occurrence.

  • 126.
    Adler, Jeremy
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Parmryd, Ingela
    Univ Gothenburg, Sahlgrenska Acad, Inst Biomed, Ingela Parmryd, Box 440, S-40530 Gothenburg, Sweden.
    Quantifying colocalization: the MOC is a hybrid coefficient - an uninformative mix of co-occurrence and correlation2019In: Journal of Cell Science, ISSN 0021-9533, E-ISSN 1477-9137, Vol. 132, no 1, article id UNSP jcs222455Article in journal (Other academic)
  • 127.
    Adler, Jeremy
    et al.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
    Parmryd, Ingela
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Quantifying colocalization: thresholding, void voxels and the H-coef2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 11, p. e111983-Article in journal (Refereed)
    Abstract [en]

    A critical step in the analysis of images is identifying the area of interest e.g. nuclei. When the nuclei are brighter than the remainder of the image an intensity can be chosen to identify the nuclei. Intensity thresholding is complicated by variations in the intensity of individual nuclei and their intensity relative to their surroundings. To compensate thresholds can be based on local rather than global intensities. By testing local thresholding methods we found that the local mean performed poorly while the Phansalkar method and a new method based on identifying the local background were superior. A new colocalization coefficient, the Hcoef, highlights a number of controversial issues. (i) Are molecular interactions measurable (ii) whether to include voxels without fluorophores in calculations, and (iii) the meaning of negative correlations. Negative correlations can arise biologically (a) because the two fluorophores are in different places or (b) when high intensities of one fluorophore coincide with low intensities of a second. The cases are distinct and we argue that it is only relevant to measure correlation using pixels that contain both fluorophores and, when the fluorophores are in different places, to just report the lack of co-occurrence and omit these uninformative negative correlation. The Hcoef could report molecular interactions in a homogenous medium. But biology is not homogenous and distributions also reflect physico-chemical properties, targeted delivery and retention. The Hcoef actually measures a mix of correlation and co-occurrence, which makes its interpretation problematic and in the absence of a convincing demonstration we advise caution, favouring separate measurements of correlation and of co-occurrence.

  • 128.
    Adler, Jeremy
    et al.
    Stockholm University, Faculty of Science, The Wenner-Gren Institute, Cell Biology.
    Shevchuk, A
    Novak, P
    Korchev, Y
    Parmryd, I
    Stockholm University, Faculty of Science, The Wenner-Gren Institute, Cell Biology.
    Single Particle Tracking in 2D Produces Gibberish: A Solution2009Conference paper (Other academic)
  • 129. Adler, Jeremy
    et al.
    Shevchuk, Andrew I
    Novak, Pavel
    Korchev, Yuri E
    Parmryd, Ingela
    Plasma membrane topography and interpretation of single-particle tracks.2010In: Nature Methods, ISSN 1548-7091, E-ISSN 1548-7105, Vol. 7, no 3, p. 170-1Article in journal (Refereed)
  • 130.
    Adler, Jeremy
    et al.
    Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology.
    Sintorn, Ida-Maria
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction.
    Strand, Robin
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Division of Visual Information and Interaction. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Information Technology, Computerized Image Analysis and Human-Computer Interaction.
    Parmryd, Ingela
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Cell Biology. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Conventional analysis of movement on non-flat surfaces like the plasma membrane makes Brownian motion appear anomalous2019In: Communications Biology, ISSN 2399-3642, Vol. 2, article id 12Article in journal (Refereed)
  • 131.
    Adler, Lennart
    et al.
    Göteborgs universitet.
    Wadskog, Ingrid
    Jönköping University, School of Engineering, JTH, Chemical Engineering.
    Ion homeostasis in Saccharomyces cerevisiae under NaCl stress2003In: Yeast stress responses / [ed] Stefan Hohmann, Willem H. Mager, Berlin: Springer , 2003, p. 201-239Chapter in book (Other academic)
  • 132.
    Adler, Marlen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Mechanisms and Dynamics of Carbapenem Resistance in Escherichia coli2014Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The emergence of extended spectrum β-lactamase (ESBL) producing Enterobacteriaceae worldwide has led to an increased use of carbapenems and may drive the development of carbapenem resistance. Existing mechanisms are mainly due to acquired carbapenemases or the combination of ESBL-production and reduced outer membrane permeability. The focus of this thesis was to study the development of carbapenem resistance in Escherichia coli in the presence and absence of acquired β-lactamases. To this end we used the resistance plasmid pUUH239.2 that caused the first major outbreak of ESBL-producing Enterobacteriaceae in Scandinavia.

    Spontaneous carbapenem resistance was strongly favoured by the presence of the ESBL-encoding plasmid and different mutational spectra and resistance levels arose for different carbapenems. Mainly, loss of function mutations in the regulators of porin expression caused reduced influx of antibiotic into the cell and in combination with amplification of β-lactamase genes on the plasmid this led to high resistance levels. We further used a pharmacokinetic model, mimicking antibiotic concentrations found in patients during treatment, to test whether ertapenem resistant populations could be selected even at these concentrations. We found that resistant mutants only arose for the ESBL-producing strain and that an increased dosage of ertapenem could not prevent selection of these resistant subpopulations. In another study we saw that carbapenem resistance can even develop in the absence of ESBL-production. We found mutants in export pumps and the antibiotic targets to give high level resistance albeit with high fitness costs in the absence of antibiotics. In the last study, we used selective amplification of β-lactamases on the pUUH239.2 plasmid by carbapenems to determine the cost and stability of gene amplifications. Using mathematical modelling we determined the likelihood of evolution of new gene functions in this region. The high cost and instability of the amplified state makes de novo evolution very improbable, but constant selection of the amplified state may balance these factors until rare mutations can establish a new function.

    In my studies I observed the influence of β-lactamases on carbapenem resistance and saw that amplification of these genes would further contribute to resistance. The rapid disappearance of amplified arrays of resistance genes in the absence of antibiotic selection may lead to the underestimation of gene amplification as clinical resistance mechanism. Amplification of β-lactamase genes is an important stepping-stone and might lead to the evolution of new resistance genes.

  • 133.
    Adler, Marlen
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Anjum, Mehreen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Andersson, Dan I.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Sandegren, Linus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Combinations of mutations in envZ, ftsI, mrdA, acrB and acrR can cause high-level carbapenem resistance in Escherichia coli2016In: Journal of Antimicrobial Chemotherapy, ISSN 0305-7453, E-ISSN 1460-2091, Vol. 71, no 5, p. 1188-1198Article in journal (Refereed)
    Abstract [en]

    The worldwide spread of ESBL-producing Enterobacteriaceae has led to an increased use of carbapenems, the group of beta-lactams with the broadest spectrum of activity. Bacterial resistance to carbapenems is mainly due to acquired carbapenemases or a combination of ESBL production and reduced drug influx via loss of outer-membrane porins. Here, we have studied the development of carbapenem resistance in Escherichia coli in the absence of beta-lactamases. We selected mutants with high-level carbapenem resistance through repeated serial passage in the presence of increasing concentrations of meropenem or ertapenem for similar to 60 generations. Isolated clones were whole-genome sequenced, and the order in which the identified mutations arose was determined in the passaged populations. Key mutations were reconstructed, and bacterial growth rates of populations and isolated clones and resistance levels to 23 antibiotics were measured. High-level resistance to carbapenems resulted from a combination of downstream effects of envZ mutation and target mutations in AcrAB-TolC-mediated drug export, together with PBP genes [mrdA (PBP2) after meropenem exposure or ftsI (PBP3) after ertapenem exposure]. Our results show that antibiotic resistance evolution can occur via several parallel pathways and that new mechanisms may appear after the most common pathways (i.e. beta-lactamases and loss of porins) have been eliminated. These findings suggest that strategies to target the most commonly observed resistance mechanisms might be hampered by the appearance of previously unknown parallel pathways to resistance.

  • 134.
    Adler, Marlen
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Anjum, Mehreen
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Berg, Otto, G.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational and Systems Biology.
    Andersson, Dan I.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Sandegren, Linus
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    High Fitness Costs and Instability of Gene Duplications Reduce Rates of Evolution of New Genes by Duplication-Divergence Mechanisms2014In: Molecular biology and evolution, ISSN 0737-4038, E-ISSN 1537-1719, Vol. 31, no 6, p. 1526-1535Article in journal (Refereed)
    Abstract [sv]

    An important mechanism for generation of new genes is by duplication-divergence of existing genes. Duplication-divergence includes several different sub-models, such as subfunctionalization where after accumulation of neutral mutations the original function is distributed between two partially functional and complementary genes, and neofunctionalization where a new function evolves in one of the duplicated copies while the old function is maintained in another copy. The likelihood of these mechanisms depends on the longevity of the duplicated state, which in turn depends on the fitness cost and genetic stability of the duplications. Here, we determined the fitness cost and stability of defined gene duplications/amplifications on a low copy number plasmid. Our experimental results show that the costs of carrying extra gene copies are substantial and that each additional kbp of DNA reduces fitness by approximately 0.15%. Furthermore, gene amplifications are highly unstable and rapidly segregate to lower copy numbers in absence of selection. Mathematical modelling shows that the fitness costs and instability strongly reduces the likelihood of both sub- and neofunctionalization, but that these effects can be off-set by positive selection for novel beneficial functions.

  • 135.
    Adlerz, Linda
    et al.
    Stockholm University, Faculty of Science, Department of Neurochemistry.
    Holback, Sofia
    Stockholm University, Faculty of Science, Department of Neurochemistry.
    Multhaup, Gerd
    Iverfeldt, Kerstin
    Stockholm University, Faculty of Science, Department of Neurochemistry.
    IGF-1-induced Processing of the Amyloid Precursor Protein Family Is Mediated by Different Signaling Pathways2007In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 282, no 14, p. 10203-10209Article in journal (Refereed)
    Abstract [en]

    The mammalian amyloid precursor protein (APP) protein family consists of the APP and the amyloid precursor-like proteins 1 and 2 (APLP1 and APLP2). The neurotoxic amyloid beta-peptide (Abeta) originates from APP, which is the only member of this protein family implicated in Alzheimer disease. However, the three homologous proteins have been proposed to be processed in similar ways and to have essential and overlapping functions. Therefore, it is also important to take into account the effects on the processing and function of the APP-like proteins in the development of therapeutic drugs aimed at decreasing the production of Abeta. Insulin and insulin-like growth factor-1 (IGF-1) have been shown to regulate APP processing and the levels of Abeta in the brain. In the present study, we show that IGF-1 increases alpha-secretase processing of endogenous APP and also increases ectodomain shedding of APLP1 and APLP2 in human SH-SY5Y neuroblastoma cells. We also investigated the role of different IGF-1-induced signaling pathways, using specific inhibitors for phosphatidylinositol 3-kinase and mitogen-activated protein kinase (MAPK). Our results indicate that phosphatidylinositol 3-kinase is involved in ectodomain shedding of APP and APLP1, but not APLP2, and that MAPK is involved only in the ectodomain shedding of APLP1.

  • 136.
    Admassie, Shimelis
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biomolecular and Organic Electronics. Linköping University, The Institute of Technology.
    Yang Nilsson, Ting
    University of Addis Ababa, Ethiopia.
    Inganas, Olle
    University of Addis Ababa, Ethiopia.
    Charge storage properties of biopolymer electrodes with (sub)tropical lignins2014In: Physical Chemistry, Chemical Physics - PCCP, ISSN 1463-9076, E-ISSN 1463-9084, Vol. 16, no 45, p. 24681-24684Article in journal (Refereed)
    Abstract [en]

    The electrochemical and charge storage properties of different lignins inside biopolymer electrodes were studied and correlated with the chemical variations of the lignins as indicated from the nuclear magnetic resonance (NMR) spectroscopic data. The varying fractions of monolignols were found to correlate with charge storage properties. It was found that as the sinapyl to guaiacyl (S/G) ratio increased both the specific capacitance and charge capacity increased considerably. This indicates that quinones generated on S-units can contribute more to charge storage in the biopolymer electrodes.

  • 137.
    Adolfsson Jörby, Sofie
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Local Agenda 21 in practice: a Swedish example2000In: Sustainable Development, ISSN 0968-0802, Vol. 8, no 4, p. 201-214Article in journal (Refereed)
  • 138.
    Adolfsson, Oscar
    Karlstad University, Faculty of Health, Science and Technology (starting 2013).
    Effekter av inkuberingstemperatur hos juvenil atlantlax (Salmo salar L.)2018Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Rising temperatures, because of climate change, will have major consequences for the world's fish populations, including the Atlantic salmon Salmo salar L. The greatest temperature changes are expected to occur during winter, which will affect S. salar since the eggs are developing during this time of year. Several studies have shown that elevated temperatures during embryogenesis cause morphological changes, in S. Salar, that are shown in later life stages. Some of these studies indicate that eggs incubated at high temperatures should generate parr with deeper bodies. To investigate whether high temperatures during the egg stage cause changes in body shape, parr from normal and high temperature incubated eggs, referred to as as “cold” and “warm” fish, respectively, were examined. A box-truss of euclidean distances between 10 landmarks on the fish body and a discriminant function analysis (DFA) was used to determine which of the distances best discriminated between the two groups. The test showed a significant discrimination between cold and warm parr regarding body shape where cold parr had greater heads and warm parr were deeper over the tail region and showed greater distances between the pelvic fin and the front attachment of the anal fin. 67,3 % of all parr where correctly classified by the test. These results support those notions that indicates that the incubation temperature is important for the morphological development of S. salar although it does not support the hypothesis.

  • 139. Adomas, Aleksandra
    et al.
    Eklund, Martin
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Johansson, Martin
    Asiegbu, Frederick O.
    Identification and analysis of differentially expressed cDNAs during nonself-competitive interaction between Phlebiopsis gigantea and Heterobasidion parviporum2006In: FEMS Microbiology Ecology, ISSN 0168-6496, E-ISSN 1574-6941, Vol. 57, no 1, p. 26-39Article in journal (Refereed)
    Abstract [en]

    The molecular factors regulating interspecific interaction between the saprotrophic biocontrol fungus Phlebiopsis gigantea and the conifer pathogen Heterobasidion parviporum were investigated. We constructed cDNA libraries and used expressed sequence tag analysis for the identification and characterization of genes expressed during the self and nonself-hyphal interaction. cDNA clones from either the pathogen or biocontrol agent were arrayed on nylon membrane filters and differentially screened with cDNA probes made from mycelia forming the barrage zone during nonself-interactions, mycelia growing outside the barrage zones or monocultures. BlastX analysis of the differentially expressed clones led to the identification of genes with diverse functions, including those with potential as virulence factors, such as hydrophobins. Because of the high sequence conservation (r2 = 0.81) between P. gigantea and H. parviporum, a selected number of genes from either fungus were used to monitor the expression profile under varying interaction conditions by virtual northern blot. The results are discussed with respect to the potential role of the induced genes during the nonself-competitive interaction for space and nutrients between P. gigantea and H. parviporum.

  • 140. Adori, Csaba
    et al.
    Barde, Swapnali
    Vas, Szilvia
    Ebner, Karl
    Su, Jie
    Svensson, Camilla
    Mathé, Aleksander A.
    Singewald, Nicolas
    Reinscheid, Rainer R.
    Uhlén, Mathias
    KTH, School of Biotechnology (BIO), Proteomics and Nanobiotechnology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Kultima, Kim
    Bagdy, Gyorgy
    Hökfelt, Tomas
    Exploring the role of neuropeptide S in the regulation of arousal: a functional anatomical study2016In: Brain Structure and Function, ISSN 1863-2653, E-ISSN 1863-2661, Vol. 221, no 7, p. 3521-3546Article in journal (Refereed)
    Abstract [en]

    Neuropeptide S (NPS) is a regulatory peptide expressed by limited number of neurons in the brainstem. The simultaneous anxiolytic and arousal-promoting effect of NPS suggests an involvement in mood control and vigilance, making the NPS-NPS receptor system an interesting potential drug target. Here we examined, in detail, the distribution of NPS-immunoreactive (IR) fiber arborizations in brain regions of rat known to be involved in the regulation of sleep and arousal. Such nerve terminals were frequently apposed to GABAergic/galaninergic neurons in the ventro-lateral preoptic area (VLPO) and to tyrosine hydroxylase-IR neurons in all hypothalamic/thalamic dopamine cell groups. Then we applied the single platform-on-water (mainly REM) sleep deprivation method to study the functional role of NPS in the regulation of arousal. Of the three pontine NPS cell clusters, the NPS transcript levels were increased only in the peri-coerulear group in sleep-deprived animals, but not in stress controls. The density of NPS-IR fibers was significantly decreased in the median preoptic nucleus-VLPO region after the sleep deprivation, while radioimmunoassay and mass spectrometry measurements showed a parallel increase of NPS in the anterior hypothalamus. The expression of the NPS receptor was, however, not altered in the VLPO-region. The present results suggest a selective activation of one of the three NPS-expressing neuron clusters as well as release of NPS in distinct forebrain regions after sleep deprivation. Taken together, our results emphasize a role of the peri-coerulear cluster in the modulation of arousal, and the importance of preoptic area for the action of NPS on arousal and sleep.

  • 141. Adrian, Rita
    et al.
    O`Reilly, Catherine M.
    Zagarese, Horacio
    Baines, Stephen B.
    Hessen, Dag O.
    Keller, Wendel
    Livingstone, David M.
    Sommaruga, Ruben
    Straile, Dietmar
    Van Donk, Ellen
    Weyhenmeyer, Gesa A.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Evolution, Limnology.
    Winder, Monika
    Lakes as sentinels of climate change2009In: Limnology and Oceanography, ISSN 0024-3590, E-ISSN 1939-5590, Vol. 54, no 6(2), p. 2283-2297Article in journal (Refereed)
    Abstract [en]

    While there is a general sense that lakes can act as sentinels of climate change, their efficacy has not been thoroughly analyzed. We identified the key response variables within a lake that act as indicators of the effects of climate change on both the lake and the catchment. These variables reflect a wide range of physical, chemical, and biological responses to climate. However, the efficacy of the different indicators is affected by regional response to climate change, characteristics of the catchment, and lake mixing regimes. Thus, particular indicators or combinations of indicators are more effective for different lake types and geographic regions. The extraction of climate signals can be further complicated by the influence of other environmental changes, such as eutrophication or acidification, and the equivalent reverse phenomena, in addition to other land-use influences. In many cases, however, confounding factors can be addressed through analytical tools such as detrending or filtering. Lakes are effective sentinels for climate change because they are sensitive to climate, respond rapidly to change, and integrate information about changes in the catchment.

  • 142. Aebersold, Ruedi
    et al.
    Agar, Jeffrey N.
    Amster, I. Jonathan
    Baker, Mark S.
    Bertozzi, Carolyn R.
    Boja, Emily S.
    Costello, Catherine E.
    Cravatt, Benjamin F.
    Fenselau, Catherine
    Garcia, Benjamin A.
    Ge, Ying
    Gunawardena, Jeremy
    Hendrickson, Ronald C.
    Hergenrother, Paul J.
    Huber, Christian G.
    Ivanov, Alexander R.
    Jensen, Ole N.
    Jewett, Michael C.
    Kelleher, Neil L.
    Kiessling, Laura L.
    Krogan, Nevan J.
    Larsen, Martin R.
    Loo, Joseph A.
    Loo, Rachel R. Ogorzalek
    Lundberg, Emma
    KTH, Centres, Science for Life Laboratory, SciLifeLab. Stanford Univ, Dept Genet, Stanford, CA 94305 USA.
    MacCoss, Michael J.
    Mallick, Parag
    Mootha, Vamsi K.
    Mrksich, Milan
    Muir, Tom W.
    Patrie, Steven M.
    Pesavento, James J.
    Pitteri, Sharon J.
    Rodriguez, Henry
    Saghatelian, Alan
    Sandoval, Wendy
    Schluter, Hartmut
    Sechi, Salvatore
    Slavoff, Sarah A.
    Smith, Lloyd M.
    Snyder, Michael P.
    Thomas, Paul M.
    Uhlen, Mathias
    Van Eyk, Jennifer E.
    Vidal, Marc
    Walt, David R.
    White, Forest M.
    Williams, Evan R.
    Wohlschlager, Therese
    Wysocki, Vicki H.
    Yates, Nathan A.
    Young, Nicolas L.
    Zhang, Bing
    How many human proteoforms are there?2018In: Nature Chemical Biology, ISSN 1552-4450, E-ISSN 1552-4469, Vol. 14, no 3, p. 206-214Article in journal (Refereed)
    Abstract [en]

    Despite decades of accumulated knowledge about proteins and their post-translational modifications (PTMs), numerous questions remain regarding their molecular composition and biological function. One of the most fundamental queries is the extent to which the combinations of DNA-, RNA-and PTM-level variations explode the complexity of the human proteome. Here, we outline what we know from current databases and measurement strategies including mass spectrometry-based proteomics. In doing so, we examine prevailing notions about the number of modifications displayed on human proteins and how they combine to generate the protein diversity underlying health and disease. We frame central issues regarding determination of protein-level variation and PTMs, including some paradoxes present in the field today. We use this framework to assess existing data and to ask the question, "How many distinct primary structures of proteins (proteoforms) are created from the 20,300 human genes?" We also explore prospects for improving measurements to better regularize protein-level biology and efficiently associate PTMs to function and phenotype.

  • 143. Aeinehband, Shahin
    et al.
    Brenner, Philip
    Stahl, Sara
    Bhat, Maria
    Fidock, Mark D.
    Khademi, Mohsen
    Olsson, Tomas
    Engberg, Goran
    Jokinen, Jussi
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    Erhardt, Sophie
    Piehl, Fredrik
    Cerebrospinal fluid kynurenines in multiple sclerosis: relation to disease course and neurocognitive symptoms2016In: Brain, behavior, and immunity, ISSN 0889-1591, E-ISSN 1090-2139, Vol. 51, p. 47-55Article in journal (Refereed)
    Abstract [en]

    Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease of the central nervous system, with a high rate of neurocognitive symptoms for which the molecular background is still uncertain. There is accumulating evidence for dysregulation of the kynurenine pathway (KP) in different psychiatric and neurodegenerative conditions. We here report the first comprehensive analysis of cerebrospinal fluid (CSF) kynurenine metabolites in MS patients of different disease stages and in relation to neurocognitive symptoms. Levels of tryptophan (TRP), kynurenine (KYN), kynurenic acid (KYNA) and quinolinic acid (QUIN) were determined with liquid chromatography mass spectrometry in cell-free CSF. At the group level MS patients (cohort 1; n = 71) did not differ in absolute levels of TRP, KYN, KYNA or QUIN as compared to non-inflammatory neurological disease controls (n = 20). Stratification of patients into different disease courses revealed that both absolute QUIN levels and the QUIN/KYN ratio were increased in relapsing-remitting MS (RRMS) patients in relapse. Interestingly, secondary progressive MS (SPMS) displayed a trend for lower TRP and KYNA, while primary progressive (PPMS) patients displayed increased levels of all metabolites, similar to a group of inflammatory neurological disease controls (n = 13). In the second cohort (n = 48), MS patients with active disease and short disease duration were prospectively evaluated for neuropsychiatric symptoms. In a supervised multivariate analysis using orthogonal projection to latent structures (OPLS-DA) depressed patients displayed higher KYNA/TRP and KYN/TRP ratios, mainly due to low TRP levels. Still, this model had low predictive value and could not completely separate the clinically depressed patients from the non-depressed MS patients. No correlation was evident for other neurocognitive measures. Taken together these results demonstrate that clinical disease activity and differences in disease courses are reflected by changes in KP metabolites. Increased QUIN levels of RRMS patients in relapse and generally decreased levels of TRP in SPMS may relate to neurotoxicity and failure of remyelination, respectively. In contrast, PPMS patients displayed a more divergent pattern more resembling inflammatory conditions such as systemic lupus erythematosus. The pattern of KP metabolites in RRMS patients could not predict neurocognitive symptoms.

  • 144.
    Aeinehband, Shahin
    et al.
    Karolinska Institutet.
    Lindblom, Rickard P. F.
    Karolinska Institutet.
    Al Nimer, Faiez
    Karolinska Institutet.
    Vijayaraghavan, Swetha
    Karolinska Institutet.
    Sandholm, Kerstin
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Khademi, Mohsen
    Karolinska Institutet.
    Olsson, Tomas
    Karolinska Institutet.
    Nilsson, Bo
    Uppsala University.
    Nilsson Ekdahl, Kristina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University.
    Darreh-Shori, Taher
    Karolinska Institutet.
    Piehl, Fredrik
    Karolinska Institutet.
    Complement Component C3 and Butyrylcholinesterase Activity Are Associated with Neurodegeneration and Clinical Disability in Multiple Sclerosis2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 4, article id e0122048Article in journal (Refereed)
    Abstract [en]

    Dysregulation of the complement system is evident in many CNS diseases but mechanisms regulating complement activation in the CNS remain unclear. In a recent large rat genomewide expression profiling and linkage analysis we found co-regulation of complement C3 immediately downstream of butyrylcholinesterase (BuChE), an enzyme hydrolyzing acetylcholine (ACh), a classical neurotransmitter with immunoregulatory effects. We here determined levels of neurofilament-light (NFL), a marker for ongoing nerve injury, C3 and activity of the two main ACh hydrolyzing enzymes, acetylcholinesterase (AChE) and BuChE, in cerebrospinal fluid (CSF) from patients with MS (n = 48) and non-inflammatory controls (n = 18). C3 levels were elevated in MS patients compared to controls and correlated both to disability and NFL. C3 levels were not induced by relapses, but were increased in patients with >= 9 cerebral lesions on magnetic resonance imaging and in patients with progressive disease. BuChE activity did not differ at the group level, but was correlated to both C3 and NFL levels in individual samples. In conclusion, we show that CSF C3 correlates both to a marker for ongoing nerve injury and degree of disease disability. Moreover, our results also suggest a potential link between intrathecal cholinergic activity and complement activation. These results motivate further efforts directed at elucidating the regulation and effector functions of the complement system in MS, and its relation to cholinergic tone.

  • 145.
    Aeppli, Christoph
    et al.
    Stockholm University, Faculty of Science, Department of Applied Environmental Science (ITM).
    Bastviken, David
    Andersson, Per
    Gustafsson, Örjan
    Stockholm University, Faculty of Science, Department of Applied Environmental Science (ITM).
    Chlorine Isotope Effects and Composition of Naturally Produced Organochlorines from Chloroperoxidases, Flavin-Dependent Halogenases, and in Forest Soil2013In: Environmental Science and Technology, ISSN 0013-936X, E-ISSN 1520-5851, Vol. 47, no 13, p. 6864-6871Article in journal (Refereed)
    Abstract [en]

    The use of stable chlorine isotopic signatures (delta Cl-37) of organochlorine compounds has been suggested as a tool to determine both their origins and transformations in the environment. Here we investigated the delta Cl-37 fractionation of two important pathways for enzymatic natural halogenation: chlorination by chloroperoxidase (CPO) and flavin-dependent halogenases (FDH). Phenolic products of CPO were highly Cl-37 depleted (delta Cl-37 = -12.6 +/- 0.9 parts per thousand); significantly more depleted than all known industrially produced organochlorine compounds (delta Cl-37 = -7 to +6 parts per thousand). In contrast, four FDH products did not exhibit any observable isotopic shifts (delta Cl-37 = -0.3 +/- 0.6 parts per thousand). We attributed the different isotopic effect to the distinctly different chlorination mechanisms employed by the two enzymes. Furthermore, the delta Cl-37 in bulk organochlorines extracted from boreal forest soils were only slightly depleted in Cl-37 relative to inorganic Cl. In contrast to previous suggestions that CPO plays a key role in production of soil organochlorines, this observation points to the additional involvement of either other chlorination pathways, or that dechlorination of naturally produced organochlorines can neutralize delta Cl-37 shifts caused by CPO chlorination. Overall, this study demonstrates that chlorine isotopic signatures are highly useful to understand sources and cycling of organochlorines in nature. Furthermore, this study presents delta Cl-37 values of FDH products as well of bulk organochlorines extracted from pristine forest soil for the first time.

  • 146.
    Aeppli, Christoph
    et al.
    Stockholm University, Faculty of Science, Department of Applied Environmental Science (ITM).
    Tysklind, Mats
    Holmstrand, Henry
    Stockholm University, Faculty of Science, Department of Applied Environmental Science (ITM).
    Gustafsson, Örjan
    Stockholm University, Faculty of Science, Department of Applied Environmental Science (ITM).
    Use of Cl and C Isotopic Fractionation to Identify Degradation and Sources of Polychlorinated Phenols: Mechanistic Study and Field Application2013In: Environmental Science and Technology, ISSN 0013-936X, E-ISSN 1520-5851, Vol. 47, no 2, p. 790-797Article in journal (Refereed)
    Abstract [en]

    The widespread use of chlorinated phenols (CPs) as a wood preservative has led to numerous contaminated sawmill sites. However, it remains challenging to assess the extent of in situ degradation of CPs. We evaluated the use of compound-specific chlorine and carbon isotope analysis (Cl- and C-CSLA) to assess CP biotransformation. In a laboratory system, we measured isotopic fractionation during oxidative 2,4,6-trichlorophenol dechlorination by representative soil enzymes (C. fumago chloroperoxidase, horseradish peroxidase, and laccase from T. versicolor). Using a mathematical model, the validity of the Rayleigh approach to evaluate apparent kinetic isotope effects (AKIE) was confirmed. A small but significant Cl-AKIE of 1.0022 +/- 0.0006 was observed for all three enzymes, consistent with a reaction pathway via a cationic radical species. For carbon, a slight inverse isotope effect was observed (C-AKIE = 0.9945 +/- 0.0019). This fractionation behavior is clearly distinguishable from reported reductive dechlorination mechanisms. Based on these results we then assessed degradation and apportioned different types of technical CP mixtures used at two former sawmill sites. To our knowledge, this is the first study that makes use of two-element CSIA to study sources and transformation of CPs in the environment.

  • 147. Aerts, R.
    et al.
    Callaghan, T. V.
    Dorrepaal, E.
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences. Systems Ecology, Department of Ecological Science, VU University Amsterdam, Amsterdam, The Netherlands.
    van Logtestijn, R. S. P.
    Cornelissen, J. H. C.
    Seasonal climate manipulations have only minor effects on litter decomposition rates and N dynamics but strong effects on litter P dynamics of sub-arctic bog species2012In: Oecologia, ISSN 0029-8549, E-ISSN 1432-1939, Vol. 170, no 3, p. 809-819Article in journal (Refereed)
    Abstract [en]

    Litter decomposition and nutrient mineralization in high-latitude peatlands are constrained by low temperatures. So far, little is known about the effects of seasonal components of climate change (higher spring and summer temperatures, more snow which leads to higher winter soil temperatures) on these processes. In a 4-year field experiment, we manipulated these seasonal components in a sub-arctic bog and studied the effects on the decomposition and N and P dynamics of leaf litter of Calamagrostis lapponica, Betula nana, and Rubus chamaemorus, incubated both in a common ambient environment and in the treatment plots. Mass loss in the controls increased in the order Calamagrostis < Betula < Rubus. After 4 years, overall mass loss in the climate-treatment plots was 10 % higher compared to the ambient incubation environment. Litter chemistry showed within each incubation environment only a few and species-specific responses. Compared to the interspecific differences, they resulted in only moderate climate treatment effects on mass loss and these differed among seasons and species. Neither N nor P mineralization in the litter were affected by the incubation environment. Remarkably, for all species, no net N mineralization had occurred in any of the treatments during 4 years. Species differed in P-release patterns, and summer warming strongly stimulated P release for all species. Thus, moderate changes in summer temperatures and/or winter snow addition have limited effects on litter decomposition rates and N dynamics, but summer warming does stimulate litter P release. As a result, N-limitation of plant growth in this sub-arctic bog may be sustained or even further promoted.

  • 148.
    Afewerki, Isaias
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre.
    Genflödet från genetiskt modifierade grödor till vilda populationer2014Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Tillämpningen av genetiskt modifierade (GM) grödor har varit utbredd över hela världen och har ökat markant sedan den första GM-grödan blev tillgänglig för kommersiellt bruk 1996. Sedan starten har det tillkommit mycket forskning kring risken för spridning av transgener från grödor till vilda populationer. För att en transgen ska kunna etableras i en vild population så måste tidiga generationer av hybrider överleva för att kunna återkorsas upprepade gånger med den vilda arten, det gör att det genetiska materialet från grödan succesivt reduceras i varje generation tills det att transgenen är det enda DNA från grödan kvar hos avkomman. För att denna process ska vara stabil krävs det en stark selektion för transgenen. Det här sättet för en gen att etableras i en population kallas för introgression och tros ha spelat en stor roll i växternas evolution. Hos vete så har man observerat introgression i ett tidigt skede med det besläktade ogräset bockvete där man även observerade en ökande fertilitet i efterföljande generationer. Hos odlad majs har man lyckats visa att majs kunnat anpassa sig till kallare klimat i nya habitat genom introgression från inhemska besläktade arter. Tecken på hybridisering och introgression har observerats hos flera grödor där selektionen har visat sig vara en av de viktigaste faktorerna för en nyintroducerad transgens fortlevnad inom en population. Migration mellan två populationer av besläktade arter, i form av pollen och fröspridning, påverkar kraftigt utsträckningen av hybridisering medan migration mellan subpopulationer inom en metapopulation påverkar effektiviteten av introgression. Om en transgen ger en förhöjd fitness till en sådan grad att hybrider framgångsrikt kan konkurrera med andra individer och reproducera sig så leder det till en spridning av genen. Trangenens interaktion med miljön påverkar också plantans fitness. En gen för insektresistens kommer att ge en ökad fitness när insektspopulationerna är stora, om insektspopulationen reduceras kraftigt så kommer genen stå för en onödig kostnad och utsättas för en negativ selektion. Den selektion som råder på åkern är anpassad för att möta våra behov av hög kvalitativ produktion av livsmedel och råvaror medan den naturliga selektionen väljer de individer som är bäst anpassade att överleva i den miljön. Sannolikheten för fixering av en transgen, skapad för att möta våra behov, in en vild population är låg, men den risken kräver ändå en noggrann utvärdering där man ser till de olika faktorerna i varje enskilt fall. 

  • 149. Affonso, Igor de Paiva
    et al.
    Karling, Leticia Cucolo
    Takemoto, Ricardo Massato
    Gomes, Luiz Carlos
    Nilsson, Per Anders
    Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Environmental and Life Sciences (from 2013). Karlstad University, Faculty of Social and Life Sciences, Department of Biology.
    Light-induced eye-fluke behavior enhances parasite life cycle2017In: Frontiers in Ecology and the Environment, ISSN 1540-9295, E-ISSN 1540-9309, Vol. 15, no 6, p. 340-341Article in journal (Refereed)
  • 150.
    Afshari Kashanian, Elisa
    Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Detection of celery (Apium graveolens) in food with Real-Time PCR2006Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    Directive EC 2003/89/EC of the European Parliament and of the Council states that certain

    ingredients and products derived there of known to cause allergen reactions must always be

    declared. Furthermore labelling is mandatory irrespective of the amount included. The National

    Food Administration therefore needs methods for monitoring the presence of allergens in food.

    Methods already exist for most of the allergens on the EU-list, but an operational method for

    celery (Apium graveolens) is missing.

    A specific DNA-method was developed, based on TaqMan Real-Time PCR with the celery

    mannitol dehydrogenase gene as target sequence. The analysis was started with homogenisation

    of the sample followed by extraction of DNA. The Real-Time PCR method was shown to be

    specific for celery, producing a 113 bp fragment with two celery varieties and negative results

    with other closely selected species commonly present together with celery in food products (12

    samples). The detection limit was 2-20 pg DNA, which corresponds to 1-7 haploid genome

    copies. When evaluated with model samples of celery in meat, a detection limit of less than

    0,01 % was determined. When used to analyse food products from the market, six out of seven

    products declared to contain celery were correctly identified as positive.

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