umu.sePublications
Change search
Refine search result
1234 1 - 50 of 156
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the 'Create feeds' function.
  • 1. Abraham, Nabil M.
    et al.
    Liu, Lei
    Jutras, Brandon Lyon
    Yadav, Akhilesh K.
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Narasimhan, Sukanya
    Gopalakrishnan, Vissagan
    Ansari, Juliana M.
    Jefferson, Kimberly K.
    Cava, Felipe
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Jacobs-Wagner, Christine
    Fikrig, Erol
    Pathogen-mediated manipulation of arthropod microbiota to promote infection2017In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 114, no 5, p. E781-E790Article in journal (Refereed)
    Abstract [en]

    Arthropods transmit diverse infectious agents; however, the ways microbes influence their vector to enhance colonization are poorly understood. Ixodes scapularis ticks harbor numerous human pathogens, including Anaplasma phagocytophilum, the agent of human granulocytic anaplasmosis. We now demonstrate that A. phagocytophilum modifies the I. scapularis microbiota to more efficiently infect the tick. A. phagocytophilum induces ticks to express Ixodes scapularis antifreeze glycoprotein (iafgp), which encodes a protein with several properties, including the ability to alter bacterial biofilm formation. IAFGP thereby perturbs the tick gut microbiota, which influences the integrity of the peritrophic matrix and gut barrier-critical obstacles for Anaplasma colonization. Mechanistically, IAFGP binds the terminal D-alanine residue of the pentapeptide chain of bacterial peptidoglycan, resulting in altered permeability and the capacity of bacteria to form biofilms. These data elucidate the molecular mechanisms by which a human pathogen appropriates an arthropod antibacterial protein to alter the gut microbiota and more effectively colonize the vector.

  • 2.
    Akopyan, Karen
    et al.
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Edgren, Tomas
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Wang-Edgren, Helen
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Rosqvist, Roland
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Fahlgren, Anna
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Wolf-Watz, Hans
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Fällman, Maria
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Translocation of surface-localized effectors in type III secretion2011In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 108, no 4, p. 1639-1644Article in journal (Refereed)
    Abstract [en]

    Pathogenic Yersinia species suppress the host immune response by using a plasmid-encoded type III secretion system (T3SS) to translocate virulence proteins into the cytosol of the target cells. T3SS-dependent protein translocation is believed to occur in one step from the bacterial cytosol to the target-cell cytoplasm through a conduit created by the T3SS upon target cell contact. Here, we report that T3SS substrates on the surface of Yersinia pseudotuberculosis are translocated into target cells. Upon host cell contact, purified YopH coated on Y. pseudotuberculosis was specifically and rapidly translocated across the target-cell membrane, which led to a physiological response in the infected cell. In addition, translocation of externally added YopH required a functional T3SS and a specific translocation domain in the effector protein. Efficient, T3SS-dependent translocation of purified YopH added in vitro was also observed when using coated Salmonella typhimurium strains, which implies that T3SS-mediated translocation of extracellular effector proteins is conserved among T3SS-dependent pathogens. Our results demonstrate that polarized T3SS-dependent translocation of proteins can be achieved through an intermediate extracellular step that can be reconstituted in vitro. These results indicate that translocation can occur by a different mechanism from the assumed single-step conduit model.

  • 3. Allgardsson, Anders
    et al.
    Berg, Lotta
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Akfur, Christine
    Hörnberg, Andreas
    Worek, Franz
    Linusson, Anna
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Ekström, Fredrik J.
    Structure of a prereaction complex between the nerve agent sarin, its biological target acetylcholinesterase, and the antidote HI-62016In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 113, no 20, p. 5514-5519Article in journal (Refereed)
    Abstract [en]

    Organophosphorus nerve agents interfere with cholinergic signaling by covalently binding to the active site of the enzyme acetylcholinesterase (AChE). This inhibition causes an accumulation of the neurotransmitter acetylcholine, potentially leading to overstimulation of the nervous system and death. Current treatments include the use of antidotes that promote the release of functional AChE by an unknown reactivation mechanism. We have used diffusion trap cryocrystallography and density functional theory (DFT) calculations to determine and analyze prereaction conformers of the nerve agent antidote HI-6 in complex with Mus musculus AChE covalently inhibited by the nerve agent sarin. These analyses reveal previously unknown conformations of the system and suggest that the cleavage of the covalent enzyme-sarin bond is preceded by a conformational change in the sarin adduct itself. Together with data from the reactivation kinetics, this alternate conformation suggests a key interaction between Glu202 and the O-isopropyl moiety of sarin. Moreover, solvent kinetic isotope effect experiments using deuterium oxide reveal that the reactivation mechanism features an isotope-sensitive step. These findings provide insights into the reactivation mechanism and provide a starting point for the development of improved antidotes. The work also illustrates how DFT calculations can guide the interpretation, analysis, and validation of crystallographic data for challenging reactive systems with complex conformational dynamics.

  • 4. Alonso-Mori, Roberto
    et al.
    Kern, Jan
    Gildea, Richard J
    Sokaras, Dimosthenis
    Weng, Tsu-Chien
    Lassalle-Kaiser, Benedikt
    Tran, Rosalie
    Hattne, Johan
    Laksmono, Hartawan
    Hellmich, Julia
    Glöckner, Carina
    Echols, Nathaniel
    Sierra, Raymond G
    Schafer, Donald W
    Sellberg, Jonas
    Kenney, Christopher
    Herbst, Ryan
    Pines, Jack
    Hart, Philip
    Herrmann, Sven
    Grosse-Kunstleve, Ralf W
    Latimer, Matthew J
    Fry, Alan R
    Messerschmidt, Marc M
    Miahnahri, Alan
    Seibert, M Marvin
    Zwart, Petrus H
    White, William E
    Adams, Paul D
    Bogan, Michael J
    Boutet, Sébastien
    Williams, Garth J
    Zouni, Athina
    Messinger, Johannes
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Glatzel, Pieter
    Sauter, Nicholas K
    Yachandra, Vittal K
    Yano, Junko
    Bergmann, Uwe
    Energy-dispersive X-ray emission spectroscopy using an X-ray free-electron laser in a shot-by-shot mode2012In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 109, no 47, p. 19103-19107Article in journal (Refereed)
    Abstract [en]

    The ultrabright femtosecond X-ray pulses provided by X-ray free-electron lasers open capabilities for studying the structure and dynamics of a wide variety of systems beyond what is possible with synchrotron sources. Recently, this "probe-before-destroy" approach has been demonstrated for atomic structure determination by serial X-ray diffraction of microcrystals. There has been the question whether a similar approach can be extended to probe the local electronic structure by X-ray spectroscopy. To address this, we have carried out femtosecond X-ray emission spectroscopy (XES) at the Linac Coherent Light Source using redox-active Mn complexes. XES probes the charge and spin states as well as the ligand environment, critical for understanding the functional role of redox-active metal sites. Kβ(1,3) XES spectra of Mn(II) and Mn(2)(III,IV) complexes at room temperature were collected using a wavelength dispersive spectrometer and femtosecond X-ray pulses with an individual dose of up to >100 MGy. The spectra were found in agreement with undamaged spectra collected at low dose using synchrotron radiation. Our results demonstrate that the intact electronic structure of redox active transition metal compounds in different oxidation states can be characterized with this shot-by-shot method. This opens the door for studying the chemical dynamics of metal catalytic sites by following reactions under functional conditions. The technique can be combined with X-ray diffraction to simultaneously obtain the geometric structure of the overall protein and the local chemistry of active metal sites and is expected to prove valuable for understanding the mechanism of important metalloproteins, such as photosystem II.

  • 5.
    Andersson, Ove
    Umeå University, Faculty of Science and Technology, Department of Physics.
    Glass-liquid transition of water at high pressure2011In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 108, no 27, p. 11013-11016Article in journal (Refereed)
    Abstract [en]

    The knowledge of the existence of liquid water under extreme conditions and its concomitant properties are important in many fields of science. Glassy water has previously been prepared by hyperquenching micron-sized droplets of liquid water and vapor deposition on a cold substrate (ASW), and its transformation to an ultraviscous liquid form has been reported on heating. A densified amorphous solid form of water, high-density amorphous ice (HDA), has also been made by collapsing the structure of ice at pressures above 1 GPa and temperatures below approximately 140 K, but a corresponding liquid phase has not been detected. Here we report results of heat capacity C(p) and thermal conductivity, in situ, measurements, which are consistent with a reversible transition from annealed HDA to ultraviscous high-density liquid water at 1 GPa and 140 K. On heating of HDA, the Cp increases abruptly by (3.4 ± 0.2) J mol-1 K-1 before crystallization starts at (153 ± 1) K. This is larger than the Cp rise at the glass to liquid transition of annealed ASW at 1 atm, which suggests the existence of liquid water under these extreme conditions.

  • 6. Aparicio, S
    et al.
    Morrison, A
    Gould, A
    Gilthorpe, Jonathan
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Chaudhuri, C
    Rigby, P
    Krumlauf, R
    Brenner, S
    Detecting conserved regulatory elements with the model genome of the Japanese puffer fish, Fugu rubripes.1995In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 92, no 5, p. 1684-1688Article in journal (Refereed)
    Abstract [en]

    Comparative vertebrate genome sequencing offers a powerful method for detecting conserved regulatory sequences. We propose that the compact genome of the teleost Fugu rubripes is well suited for this purpose. The evolutionary distance of teleosts from other vertebrates offers the maximum stringency for such evolutionary comparisons. To illustrate the comparative genome approach for F. rubripes, we use sequence comparisons between mouse and Fugu Hoxb-4 noncoding regions to identify conserved sequence blocks. We have used two approaches to test the function of these conserved blocks. In the first, homologous sequences were deleted from a mouse enhancer, resulting in a tissue-specific loss of activity when assayed in transgenic mice. In the second approach, Fugu DNA sequences showing homology to mouse sequences were tested for enhancer activity in transgenic mice. This strategy identified a neural element that mediates a subset of Hoxb-4 expression that is conserved between mammals and teleosts. The comparison of noncoding vertebrate sequences with those of Fugu, coupled to a transgenic bioassay, represents a general approach suitable for many genome projects.

  • 7.
    Arnberg, Niklas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Adenovirus E3 protein modulates leukocyte functions2013In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 110, no 50, p. 19976-19977Article in journal (Other academic)
  • 8.
    Augsten, Martin
    et al.
    Karolinska Institutet.
    Hägglöf, Christina
    Karolinska Institutet.
    Olsson, Eleonor
    Lunds universitet.
    Stolz, Claudia
    Karolinska Institutet.
    Tsagozis, Panagiotis
    Karolinska Institutet.
    Levchenko, Tetyana
    Karolinska Institutet.
    Frederick, Mitchell J
    University of Texas M.D. Anderson Cancer Center, Houston.
    Borg, Åke
    Lunds universitet.
    Micke, Patrick
    Uppsala universitet.
    Egevad, Lars
    Karolinska Institutet.
    Östman, Arne
    Karolinska Institutet.
    CXCL14 is an autocrine growth factor for fibroblasts and acts as a multi-modal stimulator of prostate tumor growth2009In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 106, no 9, p. 3414-3419Article in journal (Refereed)
    Abstract [en]

    This study explored the role of secreted fibroblast-derived factors in prostate cancer growth. Analyses of matched normal and tumor tissue revealed up-regulation of CXCL14 in cancer-associated fibroblasts of a majority of prostate cancer. Fibroblasts over-expressing CXCL14 promoted the growth of prostate cancer xenografts, and increased tumor angiogenesis and macrophage infiltration. Mechanistic studies demonstrated that autocrine CXCL14-stimulation of fibroblasts stimulate migration and ERK-dependent proliferation of fibroblasts. CXCL14-stimulation of monocyte migration was also demonstrated. Furthermore, CXCL14-producing fibroblasts, but not recombinant CXCL14, enhanced in vitro proliferation and migration of prostate cancer cells and in vivo angiogenesis. These studies thus identify CXCL14 as a novel autocrine stimulator of fibroblast growth and migration, with multi-modal tumor-stimulatory activities. In more general terms, our findings suggest autocrine stimulation of fibroblasts as a previously unrecognized mechanism for chemokine-mediated stimulation of tumor growth, and suggest a novel mechanism whereby cancer-associated fibroblasts achieve their pro-tumorigenic phenotype.

  • 9. Ausin, Israel
    et al.
    Feng, Suhua
    Yu, Chaowei
    Liu, Wanlu
    Kuo, Hsuan Yu
    Jacobsen, Elise L.
    Zhai, Jixian
    Gallego-Bartolome, Javier
    Wang, Lin
    Egertsdotter, Ulrika
    Street, Nathaniel R.
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Jacobsen, Steven E.
    Wang, Haifeng
    DNA methylome of the 20-gigabase Norway spruce genome2016In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 113, no 50, p. E8106-E8113Article in journal (Refereed)
    Abstract [en]

    DNA methylation plays important roles in many biological processes, such as silencing of transposable elements, imprinting, and regulating gene expression. Many studies of DNA methylation have shown its essential roles in angiosperms (flowering plants). However, few studies have examined the roles and patterns of DNA methylation in gymnosperms. Here, we present genome-wide high coverage single-base resolution methylation maps of Norway spruce (Picea abies) from both needles and somatic embryogenesis culture cells via whole genome bisulfite sequencing. On average, DNA methylation levels of CG and CHG of Norway spruce were higher than most other plants studied. CHH methylation was found at a relatively low level; however, at least one copy of most of the RNA-directed DNA methylation pathway genes was found in Norway spruce, and CHH methylation was correlated with levels of siRNAs. In comparison with needles, somatic embryogenesis culture cells that are used for clonally propagating spruce trees showed lower levels of CG and CHG methylation but higher level of CHH methylation, suggesting that like in other species, these culture cells show abnormal methylation patterns.

  • 10. Avall, Karin
    et al.
    Ali, Yusuf
    Leibiger, Ingo B.
    Leibiger, Barbara
    Moede, Tilo
    Paschen, Meike
    Dicker, Andrea
    Dare, Elisabetta
    Kohler, Martin
    Ilegems, Erwin
    Abdulreda, Midhat H.
    Graham, Mark
    Crooke, Rosanne M.
    Tay, Vanessa S. Y.
    Refai, Essam
    Nilsson, Stefan K.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Jacob, Stefan
    Selander, Lars
    Berggren, Per-Olof
    Juntti-Berggren, Lisa
    Apolipoprotein CIII links islet insulin resistance to beta-cell failure in diabetes2015In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 112, no 20, p. E2611-E2619Article in journal (Refereed)
    Abstract [en]

    Insulin resistance and beta-cell failure are the major defects in type 2 diabetes mellitus. However, the molecular mechanisms linking these two defects remain unknown. Elevated levels of apolipoprotein CIII (apoCIII) are associated not only with insulin resistance but also with cardiovascular disorders and inflammation. We now demonstrate that local apoCIII production is connected to pancreatic islet insulin resistance and beta-cell failure. An increase in islet apoCIII causes promotion of a local inflammatory milieu, increased mitochondrial metabolism, deranged regulation of beta-cell cytoplasmic free Ca2+ concentration ([Ca2+](i)) and apoptosis. Decreasing apoCIII in vivo results in improved glucose tolerance, and pancreatic apoCIII knockout islets transplanted into diabetic mice, with high systemic levels of the apolipoprotein, demonstrate a normal [Ca2+](i) response pattern and no hallmarks of inflammation. Hence, under conditions of islet insulin resistance, locally produced apoCIII is an important diabetogenic factor involved in impairment of beta-cell function and may thus constitute a novel target for the treatment of type 2 diabetes mellitus.

  • 11. Baba, Kyoko
    et al.
    Karlberg, Anna
    Schmidt, Julien
    Schrader, Jarmo
    Hvidsten, Torgeir
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Bako, Laszlo
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Bhalerao, Rishikesh P
    Activity-dormancy transition in the cambial meristem involves stage-specific modulation of auxin response in hybrid aspen.2011In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 108, no 8, p. 3418-23Article in journal (Refereed)
    Abstract [en]

    The molecular basis of short-day-induced growth cessation and dormancy in the meristems of perennial plants (e.g., forest trees growing in temperate and high-latitude regions) is poorly understood. Using global transcript profiling, we show distinct stage-specific alterations in auxin responsiveness of the transcriptome in the stem tissues during short-day-induced growth cessation and both the transition to and establishment of dormancy in the cambial meristem of hybrid aspen trees. This stage-specific modulation of auxin signaling appears to be controlled via distinct mechanisms. Whereas the induction of growth cessation in the cambium could involve induction of repressor auxin response factors (ARFs) and down-regulation of activator ARFs, dormancy is associated with perturbation of the activity of the SKP-Cullin-F-box(TIR) (SCF(TIR)) complex, leading to potential stabilization of repressor auxin (AUX)/indole-3-acetic acid (IAA) proteins. Although the role of hormones, such as abscisic acid (ABA) and gibberellic acid (GA), in growth cessation and dormancy is well established, our data now implicate auxin in this process. Importantly, in contrast to most developmental processes in which regulation by auxin involves changes in cellular auxin contents, day-length-regulated induction of cambial growth cessation and dormancy involves changes in auxin responses rather than auxin content.

  • 12. Baggen, Jim
    et al.
    Hurdiss, Daniel L.
    Zocher, Georg
    Mistry, Nitesh
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Roberts, Richard W.
    Slager, Jasper J.
    Guo, Hongbo
    van Vliet, Arno L. W.
    Wahedi, Maryam
    Benschop, Kimberley
    Duizer, Erwin
    de Haan, Cornelis A. M.
    de Vries, Erik
    Casasnovas, José M.
    de Groot, Raoul J.
    Arnberg, Niklas
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Stehle, Thilo
    Ranson, Neil A.
    Thibaut, Hendrik Jan
    van Kuppeveld, Frank J. M.
    Role of enhanced receptor engagement in the evolution of a pandemic acute hemorrhagic conjunctivitis virus2018In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 115, no 2, p. 397-402Article in journal (Refereed)
    Abstract [en]

    Acute hemorrhagic conjunctivitis (AHC) is a painful, contagious eye disease, with millions of cases in the last decades. Coxsackievirus A24 (CV-A24) was not originally associated with human disease, but in 1970 a pathogenic "variant" (CV-A24v) emerged, which is now the main cause of AHC. Initially, this variant circulated only in Southeast Asia, but it later spread worldwide, accounting for numerous AHC outbreaks and two pandemics. While both CV-A24 variant and nonvariant strains still circulate in humans, only variant strains cause AHC for reasons that are yet unknown. Since receptors are important determinants of viral tropism, we set out to map the CV-A24 receptor repertoire and establish whether changes in receptor preference have led to the increased pathogenicity and rapid spread of CV-A24v. Here, we identify ICAM-1 as an essential receptor for both AHC-causing and non-AHC strains. We provide a high-resolution cryo-EM structure of a virus-ICAM-1 complex, which revealed critical ICAM-1-binding residues. These data could help identify a possible conserved mode of receptor engagement among ICAM-1-binding enteroviruses and rhinoviruses. Moreover, we identify a single capsid substitution that has been adopted by all pandemic CV-A24v strains and we reveal that this adaptation enhances the capacity of CV-A24v to bind sialic acid. Our data elucidate the CV-A24v receptor repertoire and point to a role of enhanced receptor engagement in the adaptation to the eye, possibly enabling pandemic spread.

  • 13. Barlier, I
    et al.
    Kowalczyk, M
    Marchant, A
    Ljung, K
    Bhalerao, R
    Bennett, M
    Sandberg, G
    Bellini, C
    The SUR2 gene of Arabidopsis thaliana encodes the cytochrome P450 CYP83B1, a modulator of auxin homeostasis.2000In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 97, no 26Article in journal (Refereed)
    Abstract [en]

    Genetic screens have been performed to identify mutants with altered auxin homeostasis in Arabidopsis. A tagged allele of the auxin-overproducing mutant sur2 was identified within a transposon mutagenized population. The SUR2 gene was cloned and shown to encode the CYP83B1 protein, which belongs to the large family of the P450-dependent monooxygenases. SUR2 expression is up-regulated in sur1 mutants and induced by exogenous auxin in the wild type. Analysis of indole-3-acetic acid (IAA) synthesis and metabolism in sur2 plants indicates that the mutation causes a conditional increase in the pool size of IAA through up-regulation of IAA synthesis.

  • 14. Beljantseva, Jelena
    et al.
    Kudrin, Pavel
    Andresen, Liis
    Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Shingler, Victoria
    Atkinson, Gemma C.
    Tenson, Tanel
    Hauryliuk, Vasili
    Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Institute of Technology, University of Tartu, 50411 Tartu, Estonia.
    Negative allosteric regulation of Enterococcus faecalis small alarmone synthetase RelQ by single-stranded RNA2017In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 114, no 14, p. 3726-3731Article in journal (Refereed)
    Abstract [en]

    The alarmone nucleotides guanosine pentaphosphate (pppGpp) and tetraphosphate (ppGpp), collectively referred to as (p)ppGpp, are key regulators of bacterial growth, stress adaptation, pathogenicity, and antibiotic tolerance. We show that the tetrameric small alarmone synthetase (SAS) RelQ from the Gram-positive pathogen Enterococcus faecalis is a sequence-specific RNA-binding protein. RelQ's enzymatic and RNA binding activities are subject to intricate allosteric regulation. (p)ppGpp synthesis is potently inhibited by the binding of single-stranded RNA. Conversely, RelQ's enzymatic activity destabilizes the RelQ: RNA complex. pppGpp, an allosteric activator of the enzyme, counteracts the effect of RNA. Tetramerization of RelQ is essential for this regulatory mechanism, because both RNA binding and enzymatic activity are abolished by deletion of the SAS-specific C-terminal helix 5 alpha. The interplay of pppGpp binding, (p)ppGpp synthesis, and RNA binding unites two archetypal regulatory paradigms within a single protein. The mechanism is likely a prevalent but previously unappreciated regulatory switch used by the widely distributed bacterial SAS enzymes.

  • 15.
    Bentsink, Leónie
    et al.
    aDepartment of Molecular Plant Physiology, Utrecht University, Utrecht, The Netherlands; Laboratory of Genetics, Wageningen University, Wageningen, The Netherlands.
    Hanson, Johannes
    Molecular Plant Physiology, Utrecht University, Utrecht, The Netherlands; Centre for BioSystems Genomics, Wageningen, The Netherlands.
    Hanhart, Corrie J
    Wageningen, The Netherlands.
    Blankestijn-de Vries, Hetty
    Wageningen, The Netherlands.
    Coltrane, Colin
    Wageningen, The Netherlands.
    Keizer, Paul
    Wageningen, The Netherlands.
    El-Lithy, Mohamed
    Wageningen, The Netherlands.
    Alonso-Blanco, Carlos
    Madrid, Spain.
    de Andrés, M Teresa
    Madrid, Spain.
    Reymond, Matthieu
    Cologne, Germany.
    van Eeuwijk, Fred
    Wageningen, The Netherlands.
    Smeekens, Sjef
    Molecular Plant Physiology, Utrecht University, Utrecht, The Netherlands; Centre for BioSystems Genomics, Wageningen, The Netherlands.
    Koornneef, Maarten
    Wageningen, The Netherlands; Cologne, Germany.
    Natural variation for seed dormancy in Arabidopsis is regulated by additive genetic and molecular pathways2010In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 107, no 9, p. 4264-4269Article in journal (Refereed)
    Abstract [en]

    Timing of germination is presumably under strong natural selection as it determines the environmental conditions in which a plant germinates and initiates its postembryonic life cycle. To investigate how seed dormancy is controlled, quantitative trait loci (QTL) analyses has been performed in six Arabidopsis thaliana recombinant inbred line populations by analyzing them simultaneously using a mixed model QTL approach. The recombinant inbred line populations were derived from crosses between the reference accession Landsberg erecta (Ler) and accessions from different world regions. In total, 11 delay of germination (DOG) QTL have been identified, and nine of them have been confirmed by near isogenic lines (NILs). The absence of strong epistatic interactions between the different DOG loci suggests that they affect dormancy mainly by distinct genetic pathways. This was confirmed by analyzing the transcriptome of freshly harvested dry seeds of five different DOG NILs. All five DOG NILs showed discernible and different expression patterns compared with the expression of their genetic background Ler. The genes identified in the different DOG NILs represent largely different gene ontology profiles. It is proposed that natural variation for seed dormancy in Arabidopsis is mainly controlled by different additive genetic and molecular pathways rather than epistatic interactions, indicating the involvement of several independent pathways.

  • 16.
    Bergh, Johan
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Zetterström, Per
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Andersen, Peter M.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Brännström, Thomas
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Graffmo, Karin Sixtensdotter
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Jonsson, P. Andreas
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Lang, Lisa
    Stockholm, Sweden.
    Danielsson, Jens
    Stockholm, Sweden.
    Oliveberg, Mikael
    Stockholm, Sweden.
    Marklund, Stefan
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Structural and kinetic analysis of protein-aggregate strains in vivo using binary epitope mapping2015In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 112, no 14, p. 4489-4494Article in journal (Refereed)
    Abstract [en]

    Despite considerable progress in uncovering the molecular details of protein aggregation in vitro, the cause and mechanism of protein-aggregation disease remain poorly understood. One reason is that the amount of pathological aggregates in neural tissue is exceedingly low, precluding examination by conventional approaches. We present here a method for determination of the structure and quantity of aggregates in small tissue samples, circumventing the above problem. The method is based on binary epitope mapping using anti-peptide antibodies. We assessed the usefulness and versatility of the method in mice modeling the neurodegenerative disease amyotrophic lateral sclerosis, which accumulate intracellular aggregates of superoxide dismutase-1. Two strains of aggregates were identified with different structural architectures, molecular properties, and growth kinetics. Both were different from superoxide dismutase-1 aggregates generated in vitro under a variety of conditions. The strains, which seem kinetically under fragmentation control, are associated with different disease progressions, complying with and adding detail to the growing evidence that seeding, infectivity, and strain dependence are unifying principles of neurodegenerative disease.

  • 17. Bergouignan, Loretxu
    et al.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Ehrsson, H. Henrik
    Out-of-body-induced hippocampal amnesia2014In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 111, no 12, p. 4421-4426Article in journal (Refereed)
    Abstract [en]

    Theoretical models have suggested an association between the ongoing experience of the world from the perspective of one's own body and hippocampus-based episodic memory. This link has been supported by clinical reports of long-term episodic memory impairments in psychiatric conditions with dissociative symptoms, in which individuals feel detached from themselves as if having an out-of-body experience. Here, we introduce an experimental approach to examine the necessary role of perceiving the world from the perspective of one's own body for the successful episodic encoding of real-life events. While participants were involved in a social interaction, an out-of-body illusion was elicited, in which the sense of bodily self was displaced from the real body to the other end of the testing room. This condition was compared with a well-matched in-body illusion condition, in which the sense of bodily self was colocalized with the real body. In separate recall sessions, performed similar to 1 wk later, we assessed the participants' episodic memory of these events. The results revealed an episodic recollection deficit for events encoded out-of-body compared with in-body. Functional magnetic resonance imaging indicated that this impairment was specifically associated with activity changes in the posterior hippocampus. Collectively, these findings show that efficient hippocampus-based episodic-memory encoding requires a first-person perspective of the natural spatial relationship between the body and the world. Our observations have important implications for theoretical models of episodic memory, neurocognitive models of self, embodied cognition, and clinical research into memory deficits in psychiatric disorders.

  • 18. Bergström, F
    et al.
    Hägglöf, P
    Karolin, J
    Ny, Tor
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Johansson, L B
    The use of site-directed fluorophore labeling and donor-donor energy migration to investigate solution structure and dynamics in proteins.1999In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 96, no 22, p. 12477-81Article in journal (Refereed)
    Abstract [en]

    The use of molecular genetics for introducing fluorescent molecules enables the use of donor-donor energy migration to determine intramolecular distances in a variety of proteins. This approach can be applied to examine the overall molecular dimensions of proteins and to investigate structural changes upon interactions with specific target molecules. In this report, the donor-donor energy migration method is demonstrated by experiments with the latent form of plasminogen activator inhibitor type 1. Based on the known x-ray structure of plasminogen activator inhibitor type 1, three positions forming the corners of a triangle were chosen. Double Cys substitution mutants (V106C-H185C, H185C-M266C, and M266C-V106C) and corresponding single substitution mutants (V106C, H185C, and M266C) were created and labeled with a sulfhydryl specific derivative of BODIPY (=the D molecule). The side lengths of this triangle were obtained from analyses of the experimental data. The analyses account for the local anisotropic order and rotational motions of the D molecules, as well as for the influence of a partial DD-labeling. The distances, as determined from x-ray diffraction, between the C(alpha)-atoms of the positions V106C-H185C, H185C-M266C, and M266C-V106C were 60.9, 30.8, and 55.1 A, respectively. These are in good agreement with the distances of 54 +/- 4, 38 +/- 3, and 55 +/- 3 A, as determined between the BODIPY groups attached via linkers to the same residues. Although the positions of the D-molecules and the C(alpha)-atoms physically cannot coincide, there is a reasonable agreement between the methods.

  • 19. Boutte, Yohann
    et al.
    Jonsson, Kristoffer
    McFarlane, Heather E.
    Johnson, Errin
    Gendre, Delphine
    Swarup, Ranjan
    Friml, Jiri
    Samuels, Lacey
    Robert, Stephanie
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Bhalerao, Rishikesh P.
    ECHIDNA-mediated post-Golgi trafficking of auxin carriers for differential cell elongation2013In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 110, no 40, p. 16259-16264Article in journal (Refereed)
    Abstract [en]

    The plant hormone indole-acetic acid (auxin) is essential for many aspects of plant development. Auxin-mediated growth regulation typically involves the establishment of an auxin concentration gradient mediated by polarly localized auxin transporters. The localization of auxin carriers and their amount at the plasma membrane are controlled by membrane trafficking processes such as secretion, endocytosis, and recycling. In contrast to endocytosis or recycling, how the secretory pathway mediates the localization of auxin carriers is not well understood. In this study we have used the differential cell elongation process during apical hook development to elucidate the mechanisms underlying the post-Golgi trafficking of auxin carriers in Arabidopsis. We show that differential cell elongation during apical hook development is defective in Arabidopsis mutant echidna (ech). ECH protein is required for the trans-Golgi network (TGN)-mediated trafficking of the auxin influx carrier AUX1 to the plasma membrane. In contrast, ech mutation only marginally perturbs the trafficking of the highly related auxin influx carrier LIKE-AUX1-3 or the auxin efflux carrier PIN-FORMED-3, both also involved in hook development. Electron tomography reveals that the trafficking defects in ech mutant are associated with the perturbation of secretory vesicle genesis from the TGN. Our results identify differential mechanisms for the post-Golgi trafficking of de novo-synthesized auxin carriers to plasma membrane from the TGN and reveal how trafficking of auxin influx carriers mediates the control of differential cell elongation in apical hook development.

  • 20.
    Bäckström, Anna
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Lundberg, Carina
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Kersulyte, Dangeruta
    Berg, Douglas E
    Borén, Thomas
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Arnqvist, Anna
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Metastability of Helicobacter pylori bab adhesin genes and dynamics in Lewis b antigen binding2004In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 101, no 48, p. 16923-16928Article in journal (Refereed)
  • 21. Caminade, Cyril
    et al.
    Kovats, Sari
    Rocklöv, Joacim
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Tompkins, Adrian M
    Morse, Andrew P
    Colón-González, Felipe J
    Stenlund, Hans
    Martens, Pim
    Lloyd, Simon J
    Impact of climate change on global malaria distribution2014In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 111, no 9, p. 3286-3291Article in journal (Refereed)
    Abstract [en]

    Malaria is an important disease that has a global distribution and significant health burden. The spatial limits of its distribution and seasonal activity are sensitive to climate factors, as well as the local capacity to control the disease. Malaria is also one of the few health outcomes that has been modeled by more than one research group and can therefore facilitate the first model intercomparison for health impacts under a future with climate change. We used bias-corrected temperature and rainfall simulations from the Coupled Model Intercomparison Project Phase 5 climate models to compare the metrics of five statistical and dynamical malaria impact models for three future time periods (2030s, 2050s, and 2080s). We evaluated three malaria outcome metrics at global and regional levels: climate suitability, additional population at risk and additional person-months at risk across the model outputs. The malaria projections were based on five different global climate models, each run under four emission scenarios (Representative Concentration Pathways, RCPs) and a single population projection. We also investigated the modeling uncertainty associated with future projections of populations at risk for malaria owing to climate change. Our findings show an overall global net increase in climate suitability and a net increase in the population at risk, but with large uncertainties. The model outputs indicate a net increase in the annual person-months at risk when comparing from RCP2.6 to RCP8.5 from the 2050s to the 2080s. The malaria outcome metrics were highly sensitive to the choice of malaria impact model, especially over the epidemic fringes of the malaria distribution.

  • 22. Campbell, D
    et al.
    Eriksson, Mats-Jerry
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Oquist, Gunnar
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Gustafsson, Petter
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Clarke, A K
    The cyanobacterium Synechococcus resists UV-B by exchanging photosystem II reaction-center D1 proteins1998In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 95, no 1, p. 364-369Article in journal (Refereed)
    Abstract [en]

    Current ambient UV-B levels can significantly depress productivity in aquatic habitats, largely because UV-B inhibits several steps of photosynthesis, including the photooxidation of water catalyzed by photosystem II, We show that upon UV-B exposure the cyanobacterium Synechococcus sp, PCC 7942 rapidly changes the expression of a family of three psbA genes encoding photosystem II D1 proteins, In wild-type cells the psbAI gene is expressed constitutively, but strong accumulations of psbAII and psbAIII transcripts are induced within 15 min of moderate UV-B exposure (0.4 W/m(2)), This transcriptional response causes an exchange of two distinct photosystem II D1 proteins, D1:1 is encoded by psbAI, but on UV-B exposure, it is largely replaced by the alternate D1:2 form, encoded by both psbAII and psbAIII, The total content of D1 and other photosystem II reaction center protein, D2, remained unchanged throughout the UV exposure, as did the content and composition of the phycobilisome, Wild-type cells suffered only slight transient inhibition of photosystem II function under UV-B exposure, In marked contrast, under the same UV-B treatment, a mutant strain expressing only psbAI suffered severe (40%) and sustained inhibition of photosystem II function, Another mutant strain with constitutive expression of psbAII and psbAIII was almost completely resistant to the UV-B treatment, showing no inhibition of photosystem II function and only a slight drop in electron transport, In Synechococcus the rapid exchange of alternate D1 forms, therefore, accounts for much of the cellular resistance to UV-B inhibition of photosystem II activity and photosynthetic electron transport, This molecular plasticity may be an important element in community-level responses to UV-B, where susceptibility to UV-B inhibition of photosynthesis changes diurnally.

  • 23. Catoire, MilSNe
    et al.
    Alex, Sheril
    Paraskevopulos, Nicolas
    Mattijssen, Frits
    Evers-van Gogh, Inkie
    Schaart, Gert
    Jeppesen, Jacob
    Kneppers, Anita
    Mensink, Marco
    Voshol, Peter J.
    Olivecrona, Gunilla
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Physiological chemistry.
    Tan, Nguan Soon
    Hesselink, Matthijs K. C.
    Berbee, Jimmy F.
    Rensen, Patrick C. N.
    Kalkhoven, Eric
    Schrauwen, Patrick
    Kersten, Sander
    Fatty acid-inducible ANGPTL4 governs lipid metabolic response to exercise2014In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 111, no 11, p. E1043-E1052Article in journal (Refereed)
    Abstract [en]

    Physical activity increases energy metabolism in exercising muscle. Whether acute exercise elicits metabolic changes in nonexercising muscles remains unclear. We show that one of the few genes that is more highly induced in nonexercising muscle than in exercising human muscle during acute exercise encodes angiopoietin-like 4 (ANGPTL4), an inhibitor of lipoprotein lipase-mediated plasma triglyceride clearance. Using a combination of human, animal, and in vitro data, we show that induction of ANGPTL4 in nonexercising muscle is mediated by elevated plasma free fatty acids via peroxisome proliferator-activated receptor-delta, presumably leading to reduced local uptake of plasma triglyceride-derived fatty acids and their sparing for use by exercising muscle. In contrast, the induction of ANGPTL4 in exercising muscle likely is counteracted via AMP-activated protein kinase (AMPK)-mediated down-regulation, promoting the use of plasma triglycerides as fuel for active muscles. Our data suggest that nonexercising muscle and the local regulation of ANGPTL4 via AMPK and free fatty acids have key roles in governing lipid homeostasis during exercise.

  • 24.
    Chabes, Andrei
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Domkin, Vladimir
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Larsson, Göran
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Liu, Aimin
    Gräslund, Astrid
    Wijmenga, Sybren S
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Thelander, Lars
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Yeast ribonucleotide reductase has a heterodimeric iron-radical-containing subunit2000In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 97, no 6, p. 2474-2479Article in journal (Refereed)
    Abstract [en]

    Ribonucleotide reductase (RNR) catalyzes the de novo synthesis of deoxyribonucleotides. Eukaryotes have an alpha(2)beta(2) form of RNR consisting of two homodimeric subunits, proteins R1 (alpha(2)) and R2 (beta(2)). The R1 protein is the business end of the enzyme containing the active site and the binding sites for allosteric effectors. The R2 protein is a radical storage device containing an iron center-generated tyrosyl free radical. Previous work has identified an RNR protein in yeast, Rnr4p, which is homologous to other R2 proteins but lacks a number of conserved amino acid residues involved in iron binding. Using highly purified recombinant yeast RNR proteins, we demonstrate that the crucial role of Rnr4p (beta') is to fold correctly and stabilize the radical-storing Rnr2p by forming a stable 1:1 Rnr2p/Rnr4p complex. This complex sediments at 5.6 S as a betabeta' heterodimer in a sucrose gradient. In the presence of Rnr1p, both polypeptides of the Rnr2p/Rnr4p heterodimer cosediment at 9.7 S as expected for an alpha(2)betabeta' heterotetramer, where Rnr4p plays an important role in the interaction between the alpha(2) and the betabeta ' subunits. The specific activity of the Rnr2p complexed with Rnr4p is 2,250 nmol deoxycytidine 5'-diphosphate formed per min per mg, whereas the homodimer of Rnr2p shows no activity. This difference in activity may be a consequence of the different conformations of the inactive homodimeric Rnr2p and the active Rnr4p-bound form, as shown by CD spectroscopy. Taken together, our results show that the Rnr2p/Rnr4p heterodimer is the active form of the yeast RNR small subunit.

  • 25.
    Chapman, K B
    et al.
    Umeå University, Faculty of Medicine, Molecular Biology.
    Byström, Anders S
    Umeå University, Faculty of Medicine, Molecular Biology. Umeå University, Faculty of Science and Technology, Molecular Biology (Faculty of Science and Technology).
    Boeke, J D
    Initiator methionine tRNA is essential for Ty1 transposition in yeast1992In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 89, no 8, p. 3236-3240Article in journal (Refereed)
    Abstract [en]

    The yeast retrotransposon Ty1 transposes through an RNA intermediate by a mechanism similar to that of retroviral reverse transcription and integration. Ty1 RNA contains a putative minus strand primer binding site (-PBS) that is complementary to the 3' acceptor stem of the initiator methionine tRNA (tRNA(iMet)). Here we demonstrate that the tRNA(iMet) is used as a primer for Ty1 reverse transcription. Mutations in the Ty1 element that alter 5 of 10 nucleotides that are complementary to the tRNA(iMet) abolish Ty1 transposition, even though they are silent with regard to Ty1 protein coding. We have constructed a yeast strain lacking wild-type tRNA(iMet) that is dependent on a mutant derivative of tRNA(iMet) that has an altered acceptor stem sequence, engineered to restore homology with the Ty1 -PBS mutant. The compensatory mutations made in the tRNA(iMet) alleviate the transposition defect of the Ty1 -PBS mutant. The mutant and wild-type tRNA(iMet) are enriched within Ty1 virus-like particles irrespective of complementarity to the Ty1 -PBS. Thus, complementarity between the Ty1 -PBS and tRNA(iMet) is essential for transposition but is not necessary for packaging of the tRNA inside virus-like particles.

  • 26. Chen, Cong
    et al.
    Tao, Zhensheng
    Carr, Adra
    Matyba, Piotr
    Umeå University, Faculty of Science and Technology, Department of Physics. JILA, Department of Physics, University of Colorado and National Institute of Standards and Technology, Boulder, CO 80309, United States.
    Szilvasi, Tibor
    Emmerich, Sebastian
    Piecuch, Martin
    Keller, Mark
    Zusin, Dmitriy
    Eich, Steffen
    Rollinger, Markus
    Youa, Wenjing
    Mathias, Stefan
    Thumm, Uwe
    Mavrikakis, Manos
    Aeschlimann, Martin
    Oppeneer, Peter M.
    Kapteyn, Henry
    Murnane, Margaret
    Distinguishing attosecond electron-electron scattering and screening in transition metals2017In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 114, no 27, p. E5300-E5307Article in journal (Refereed)
    Abstract [en]

    Electron-electron interactions are the fastest processes in materials, occurring on femtosecond to attosecond timescales, depending on the electronic band structure of the material and the excitation energy. Such interactions can play a dominant role in light-induced processes such as nano-enhanced plasmonics and catalysis, light harvesting, or phase transitions. However, to date it has not been possible to experimentally distinguish fundamental electron interactions such as scattering and screening. Here, we use sequences of attosecond pulses to directly measure electron-electron interactions in different bands of different materials with both simple and complex Fermi surfaces. By extracting the time delays associated with photoemission we show that the lifetime of photoelectrons from the d band of Cu are longer by similar to 100 as compared with those from the same band of Ni. We attribute this to the enhanced electron-electron scattering in the unfilled d band of Ni. Using theoretical modeling, we can extract the contributions of electron-electron scattering and screening in different bands of different materials with both simple and complex Fermi surfaces. Our results also show that screening influences high-energy photoelectrons (approximate to 20 eV) significantly less than low-energy photoelectrons. As a result, high-energy photoelectrons can serve as a direct probe of spin-dependent electron-electron scattering by neglecting screening. This can then be applied to quantifying the contribution of electron interactions and screening to low-energy excitations near the Fermi level. The information derived here provides valuable and unique information for a host of quantum materials.

  • 27. Cheng, Fang
    et al.
    Shen, Yue
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics. Centre for Heart Lung Innovation, St. Paul ’ s Hospital, Vancouver, BC, Canada V6Z 1Y6; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada V6Z 1Y6.
    Mohanasundaram, Ponnuswamy
    Lindstrom, Michelle
    Ivaska, Johanna
    Ny, Tor
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Eriksson, John E.
    Vimentin coordinates fibroblast proliferation and keratinocyte differentiation in wound healing via TGF-beta-Slug signaling2016In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 113, no 30, p. E4320-E4327Article in journal (Refereed)
    Abstract [en]

    Vimentin has been shown to be involved in wound healing, but its functional contribution to this process is poorly understood. Here we describe a previously unrecognized function of vimentin in coordinating fibroblast proliferation and keratinocyte differentiation during wound healing. Loss of vimentin led to a severe deficiency in fibroblast growth, which in turn inhibited the activation of two major initiators of epithelial-mesenchymal transition (EMT), TGF-beta 1 signaling and the Zinc finger transcriptional repressor protein Slug, in vimentin-deficient (VIM-/-) wounds. Correspondingly, VIM-/- wounds exhibited loss of EMT-like keratinocyte activation, limited keratinization, and slow reepithelialization. Furthermore, the fibroblast deficiency abolished collagen accumulation in the VIM-/- wounds. Vimentin reconstitution in VIM-/- fibroblasts restored both their proliferation and TGF-beta 1 production. Similarly, restoring paracrine TGF-beta-Slug-EMT signaling reactivated the transdifferentiation of keratinocytes, reviving their migratory properties, a critical feature for efficient healing. Our results demonstrate that vimentin orchestrates the healing by controlling fibroblast proliferation, TGF-beta 1-Slug signaling, collagen accumulation, and EMT processing, all of which in turn govern the required keratinocyte activation.

  • 28. CLARKE, AK
    et al.
    HURRY, VM
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Gustafsson, Petter
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Oquist, Gunnar
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    2 FUNCTIONALLY DISTINCT FORMS OF THE PHOTOSYSTEM-II REACTION-CENTER PROTEIN D1 IN THE CYANOBACTERIUM SYNECHOCOCCUS SP PCC 79421993In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 90, no 24, p. 11985-11989Article in journal (Refereed)
    Abstract [en]

    The cyanobacterium Synechococcus sp. PCC 7942 possesses a small psbA multigene family that codes for two distinct forms of the photosystem II reaction-center protein D1 (D1:1 and D1:2). We showed previously that the normally predominant D1 form (D1:1) was rapidly replaced with the alternative D1:2 when cells adapted to a photon irradiance of 50 mumol/m-2.s-1 are shifted to 500 mumol.m-2.s-1 and that this interchange was readily reversible once cells were allowed to recover under the original growth conditions. By using the psbA inactivation mutants R2S2C3 and R2K1 (which synthesize only D1:1 and D1:2, respectively), we showed that this interchange between D1 forms was essential for limiting the degree of photoinhibition as well as enabling a rapid recovery of photosynthesis. In this report, we have extended these findings by examining whether any intrinsic functional differences exist between the two D1 forms that may afford increased resistance to photoinhibition. Initial studies on the rate of D1 degradation at three photon-irradiances (50, 200, and 500 mumol.m-2.s-1) showed that the rates of degradation for both D1 forms increase with increasing photon flux density but that there was no significant difference between D1:1 and D1:2. Analysis of light-response curves for oxygen evolution for the mutants R2S2C3 and R2K1 revealed that cells with photosystem II reaction centers containing D1:2 have a higher apparent quantum yield (almost-equal-to 25%) than cells possessing D1:1. Further studies using chlorophyll a fluorescence measurements confirmed that R2K1 has a higher photochemical yield than R2S2C3; that is, a more efficient conversion of excitation energy from photon absorption into photochemistry. We believe that the higher photochemical efficiency of reaction centers containing D1:2 is causally related to the preferential induction of D1:2 at high light and thus may be an integral component of the protection mechanism within Synechococcus sp. PCC 7942 against photoinhibition.

  • 29. CLARKE, AK
    et al.
    SOITAMO, A
    Gustafsson, Petter
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Oquist, Gunnar
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    RAPID INTERCHANGE BETWEEN 2 DISTINCT FORMS OF CYANOBACTERIAL PHOTOSYSTEM-II REACTION-CENTER PROTEIN-D1 IN RESPONSE TO PHOTOINHIBITION1993In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 90, no 21, p. 9973-9977Article in journal (Refereed)
    Abstract [en]

    We have studied photoinhibition of photosynthesis in the cyanobacterium Synechococcus sp. PCC 7942, which possesses two distinct forms of the photosystem II reaction-center protein D1 (D1:1 and D1:2). We report here that when cells adapted to a growth irradiance of 50 mumol.m-2.s-1 are exposed to an irradiance of 500 mumol.m-2.s-1, the normally predominant D1 form (D1:1) is rapidly replaced with the alternative D1:2. This interchange is not only complete within the first hour of photoinhibition but is also fully reversible once cells are returned to 50 mumol.m-2.s-1. By using a mutant that synthesizes only D1:1, we show that the failure to replace D1:1 with D1:2 during photoinhibition results in severe loss of photosynthetic activity as well as a diminished capacity to recover after the stress period. We believe that this interchange between D1 forms may constitute an active component in a protection mechanism unique among photosynthetic organisms that enables cyanobacteria to effectively cope with and recover from photoinhibition.

  • 30.
    Colucci, Francesco
    et al.
    Umeå University, Faculty of Medicine, Molecular Biology.
    Bergman, Marie-Louise
    Umeå University, Faculty of Medicine, Molecular Biology.
    Penha-Gonçalves, Carlos
    Umeå University, Faculty of Medicine, Molecular Biology.
    Cilio, Corrado M
    Umeå University, Faculty of Medicine, Molecular Biology.
    Holmberg, Dan
    Umeå University, Faculty of Medicine, Molecular Biology.
    Apoptosis resistance of nonobese diabetic peripheral lymphocytes linked to the Idd5 diabetes susceptibility region1997In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 94, no 16, p. 8670-8674Article in journal (Refereed)
    Abstract [en]

    Defects in lymphocyte apoptosis may lead to autoimmune disorders and contribute to the pathogenesis of type 1 diabetes. Lymphocytes of nonobese diabetic (NOD) mice, an animal model of autoimmune diabetes, have been found resistant to various apoptosis signals, including the alkylating drug cyclophosphamide. Using an F2 intercross between the apoptosis-resistant NOD mouse and the apoptosis-susceptible C57BL/6 mouse, we define a major locus controlling the apoptosis-resistance phenotype and demonstrate its linkage (logarithm of odds score = 3.9) to a group of medial markers on chromosome 1. The newly defined gene cannot be dissociated from Ctla4 and Cd28 and in fact marks a 20-centimorgan region encompassing Idd5, a previously postulated diabetes susceptibility locus. Interestingly, we find that the CTLA-4 (cytotoxic T lymphocyte-associated antigen 4) and the CD28 costimulatory molecules are defectively expressed in NOD mice, suggesting that one or both of these molecules may be involved in the control of apoptosis resistance and, in turn, in diabetes susceptibility.

  • 31. Couthouis, Julien
    et al.
    Hart, Michael P
    Shorter, James
    DeJesus-Hernandez, Mariely
    Erion, Renske
    Oristano, Rachel
    Liu, Annie X
    Ramos, Daniel
    Jethava, Niti
    Hosangadi, Divya
    Epstein, James
    Chiang, Ashley
    Diaz, Zamia
    Nakaya, Tadashi
    Ibrahim, Fadia
    Kim, Hyung-Jun
    Solski, Jennifer A
    Williams, Kelly L
    Mojsilovic-Petrovic, Jelena
    Ingre, Caroline
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Boylan, Kevin
    Graff-Radford, Neill R
    Dickson, Dennis W
    Clay-Falcone, Dana
    Elman, Lauren
    McCluskey, Leo
    Greene, Robert
    Kalb, Robert G
    Lee, Virginia M-Y
    Trojanowski, John Q
    Ludolph, Albert
    Robberecht, Wim
    Andersen, Peter M
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Neurology.
    Nicholson, Garth A
    Blair, Ian P
    King, Oliver D
    Bonini, Nancy M
    Van Deerlin, Vivianna
    Rademakers, Rosa
    Mourelatos, Zissimos
    Gitler, Aaron D
    A yeast functional screen predicts new candidate ALS disease genes2011In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 108, no 52, p. 20881-20890Article in journal (Refereed)
    Abstract [en]

    Amyotrophic lateral sclerosis (ALS) is a devastating and universally fatal neurodegenerative disease. Mutations in two related RNA-binding proteins, TDP-43 and FUS, that harbor prion-like domains, cause some forms of ALS. There are at least 213 human proteins harboring RNA recognition motifs, including FUS and TDP-43, raising the possibility that additional RNA-binding proteins might contribute to ALS pathogenesis. We performed a systematic survey of these proteins to find additional candidates similar to TDP-43 and FUS, followed by bioinformatics to predict prion-like domains in a subset of them. We sequenced one of the segenes, TAF15, in patients with ALS and identified missense variants, which were absent in a large number of healthy controls. These disease-associated variants of TAF15 caused formation of cytoplasmic foci when expressed in primary cultures of spinal cord neurons. Very similar to TDP-43 and FUS, TAF15 aggregated in vitro and conferred neurodegeneration in Drosophila, with the ALS-linked variants having amore severe effect than wild type. Immunohistochemistry of postmortem spinal cord tissue revealed mislocalization of TAF15 in motor neurons of patients with ALS. We propose that aggregation-prone RNA-binding proteins might contribute very broadly to ALS pathogenesis and the genes identified in our yeast functional screen, coupled with prion-like domain prediction analysis, now provide a powerful resource to facilitate ALS disease gene discovery.

  • 32. Dago, Angel E
    et al.
    Schug, Alexander
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Procaccini, Andrea
    Hoch, James A
    Weigt, Martin
    Szurmant, Hendrik
    Structural basis of histidine kinase autophosphorylation deduced by integrating genomics, molecular dynamics, and mutagenesis2012In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 109, no 26, p. E1733-E1742Article in journal (Refereed)
    Abstract [en]

    Signal transduction proteins such as bacterial sensor histidine kinases, designed to transition between multiple conformations, are often ruled by unstable transient interactions making structural characterization of all functional states difficult. This study explored the inactive and signal-activated conformational states of the two catalytic domains of sensor histidine kinases, HisKA and HATPase. Direct coupling analyses, a global statistical inference approach, was applied to >13,000 such domains from protein databases to identify residue contacts between the two domains. These contacts guided structural assembly of the domains using MAGMA, an advanced molecular dynamics docking method. The active conformation structure generated by MAGMA simultaneously accommodated the sequence derived residue contacts and the ATP-catalytic histidine contact. The validity of this structure was confirmed biologically by mutation of contact positions in the Bacillus subtilis sensor histidine kinase KinA and by restoration of activity in an inactive KinA(HisKA):KinD(HATPase) hybrid protein. These data indicate that signals binding to sensor domains activate sensor histidine kinases by causing localized strain and unwinding at the end of the C-terminal helix of the HisKA domain. This destabilizes the contact positions of the inactive conformation of the two domains, identified by previous crystal structure analyses and by the sequence analysis described here, inducing the formation of the active conformation. This study reveals that structures of unstable transient complexes of interacting proteins and of protein domains are accessible by applying this combination of cross-validating technologies.

     

  • 33. Danielsson, Jens
    et al.
    Awad, Wael
    Saraboji, Kadhirvel
    Kurnik, Martin
    Lang, Lisa
    Leinartaite, Lina
    Marklund, Stefan L
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Logan, Derek T
    Oliveberg, Mikael
    Global structural motions from the strain of a single hydrogen bond2013In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 110, no 10, p. 3829-3834Article in journal (Refereed)
    Abstract [en]

    The origin and biological role of dynamic motions of folded enzymes is not yet fully understood. In this study, we examine the molecular determinants for the dynamic motions within the beta-barrel of superoxide dismutase 1 (SOD1), which previously were implicated in allosteric regulation of protein maturation and also pathological misfolding in the neurodegenerative disease amyotrophic lateral sclerosis. Relaxation-dispersion NMR, hydrogen/deuterium exchange, and crystallographic data show that the dynamic motions are induced by the buried H43 side chain, which connects the backbones of the Cu ligand H120 and T39 by a hydrogen-bond linkage through the hydrophobic core. The functional role of this highly conserved H120-H43-T39 linkage is to strain H120 into the correct geometry for Cu binding. Upon elimination of the strain by mutation H43F, the apo protein relaxes through hydrogen-bond swapping into a more stable structure and the dynamic motions freeze out completely. At the same time, the holo protein becomes energetically penalized because the twisting back of H120 into Cu-bound geometry leads to burial of an unmatched backbone carbonyl group. The question then is whether this coupling between metal binding and global structural motions in the SOD1 molecule is an adverse side effect of evolving viable Cu coordination or plays a key role in allosteric regulation of biological function, or both?

  • 34. Dietrich, Nicole
    et al.
    Rohde, Manfred
    Geffers, Robert
    Kröger, Andrea
    Hauser, Hansjörg
    Weiss, Siegfried
    Gekara, Nelson O
    Helmholtz-Centre for Infection Research, 38124 Braunschweig, Germany.
    Mast cells elicit proinflammatory but not type I interferon responses upon activation of TLRs by bacteria.2010In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 107, no 19, p. 8748-8753Article in journal (Refereed)
    Abstract [en]

    Balanced induction of proinflammatory and type I IFN responses upon activation of Toll-like receptors (TLRs) determines the outcome of microbial infections and the pathogenesis of autoimmune and other inflammatory diseases. Mast cells, key components of the innate immune system, are known for their debilitating role in allergy and autoimmunity. However, their role in antimicrobial host defenses is being acknowledged increasingly. How mast cells interact with microbes and the nature of responses triggered thereby is not well characterized. Here we show that in response to TLR activation by Gram-positive and -negative bacteria or their components, mast cells elicit proinflammatory but not type I IFN responses. We demonstrate that in mast cells, bound bacteria and TLR ligands remain trapped at the cell surface and do not undergo internalization, a prerequisite for type I IFN induction. Such cells, however, can elicit type I IFNs in response to vesicular stomatitis virus which accesses the cytosolic retinoic acid-inducible gene I receptor. Although important for antiviral immunity, a strong I IFN response is known to contribute to pathogenesis of several bacterial pathogens such as Listeria monocytogenes. Interestingly, we observed that the mast cell-dependent neutrophil mobilization upon L. monocytogenes infection is highly impaired by IFN-beta. Thus, the fact that mast cells, although endowed with the capacity to elicit type I IFNs in response to viral infection, elicit only proinflammatory responses upon bacterial infection shows that mast cells, key effector cells of the innate immune system, are well adjusted for optimal antibacterial and antiviral responses.

  • 35. Doyle, Siamsa M.
    et al.
    Haeger, Ash
    Vain, Thomas
    Rigal, Adeline
    Viotti, Corrado
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Langowska, Malgorzata
    Ma, Qian
    Friml, Jiri
    Raikhel, Natasha V.
    Hicks, Glenn R.
    Robert, Stephanie
    An early secretory pathway mediated by GNOM-LIKE 1 and GNOM is essential for basal polarity establishment in Arabidopsis thaliana2015In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 112, no 7, p. E806-E815Article in journal (Refereed)
    Abstract [en]

    Spatial regulation of the plant hormone indole-3-acetic acid (IAA, or auxin) is essential for plant development. Auxin gradient establishment is mediated by polarly localized auxin transporters, including PIN-FORMED (PIN) proteins. Their localization and abundance at the plasma membrane are tightly regulated by endo-membrane machinery, especially the endocytic and recycling pathways mediated by the ADP ribosylation factor guanine nucleotide exchange factor (ARF-GEF) GNOM. We assessed the role of the early secretory pathway in establishing PIN1 polarity in Arabidopsis thaliana by pharmacological and genetic approaches. We identified the compound endosidin 8 (ES8), which selectively interferes with PIN1 basal polarity without altering the polarity of apical proteins. ES8 alters the auxin distribution pattern in the root and induces a strong developmental phenotype, including reduced root length. The ARF-GEF-defective mutants gnom-like 1 (gnl1-1) and gnom (van7) are significantly resistant to ES8. The compound does not affect recycling or vacuolar trafficking of PIN1 but leads to its intracellular accumulation, resulting in loss of PIN1 basal polarity at the plasma membrane. Our data confirm a role for GNOM in endoplasmic reticulum (ER)-Golgi trafficking and reveal that a GNL1/GNOM-mediated early secretory pathway selectively regulates PIN1 basal polarity establishment in a manner essential for normal plant development.

  • 36. Drotz, Stina Harrysson
    et al.
    Sparrman, Tobias
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Nilsson, Mats B
    Schleucher, Jürgen
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Öquist, Mats G
    Both catabolic and anabolic heterotrophic microbial activity proceed in frozen soils2010In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 107, no 49, p. 21046-21051Article in journal (Refereed)
    Abstract [en]

    A large proportion of the global soil carbon pool is stored in soils of high-latitude ecosystems in which microbial processes and production of greenhouse gases proceed during the winter months. It has been suggested that microorganisms have limited ability to sequester substrates at temperatures around and below 0 °C and that a metabolic shift to dominance of catabolic processes occurs around these temperatures. However, there are contrary indications that anabolic processes can proceed, because microbial growth has been observed at far lower temperatures. Therefore, we investigated the utilization of the microbial substrate under unfrozen and frozen conditions in a boreal forest soil across a temperature range from -9 °C to +9 °C, by using gas chromatography-isotopic ratio mass spectrometry and (13)C magic-angle spinning NMR spectroscopy to determine microbial turnover and incorporation of (13)C-labeled glucose. Our results conclusively demonstrate that the soil microorganisms maintain both catabolic (CO(2) production) and anabolic (biomass synthesis) processes under frozen conditions and that no significant differences in carbon allocation from [(13)C]glucose into [(13)C]CO(2) and cell organic (13)C-compounds occurred between +9 °C and -4 °C. The only significant metabolic changes detected were increased fluidity of the cell membranes synthesized at frozen conditions and increased production of glycerol in the frozen samples. The finding that the processes in frozen soil are similar to those in unfrozen soil has important implications for our general understanding and conceptualization of soil carbon dynamics in high-latitude ecosystems.

  • 37.
    Dynesius, Mats
    et al.
    Umeå University, Faculty of Science and Technology, Ecology and Environmental Science.
    Jansson, Roland
    Umeå University, Faculty of Science and Technology, Ecology and Environmental Science.
    Evolutionary consequences of changes in species geographical distributions driven by Milankovitch climate oscillations2000In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 97, p. 9115-9120Article in journal (Refereed)
    Abstract [en]

    We suggest Milankovitch climate oscillations as a common cause for geographical patterns in species diversity, species' range sizes, polyploidy, and the degree of specialization and dispersability of organisms. Periodical changes in the orbit of the Earth cause climatic changes termed Milankovitch oscillations, leading to large changes in the size and location of species' geographical distributions. We name these recurrent changes ‘‘orbitally forced species' range dynamics'' (ORD). The magnitude of ORD varies in space and time. ORD decreases gradual speciation (attained by gradual changes over many generations), increases range sizes and the proportions of species formed by polyploidy and other ‘‘abrupt'' mechanisms, selects against specialization, and favor dispersability. Large ORD produces species prone neither to extinction nor gradual speciation. ORD increases with latitude. This produces latitudinal patterns, among them the gradient in species diversity and species' range sizes (Rapoport's rule). Differential ORD and its evolutionary consequences call for new conservation strategies on the regional to global scale.

  • 38. Dörr, Tobias
    et al.
    Alvarez, Laura
    Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Delgado, Fernanda
    Davis, Brigid M.
    Cava, Felipe
    Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Waldor, Matthew K.
    A cell wall damage response mediated by a sensor kinase/response regulator pair enables beta-lactam tolerance2016In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 113, no 2, p. 404-409Article in journal (Refereed)
    Abstract [en]

    The bacterial cell wall is critical for maintenance of cell shape and survival. Following exposure to antibiotics that target enzymes required for cell wall synthesis, bacteria typically lyse. Although several cell envelope stress response systems have been well described, there is little knowledge of systems that modulate cell wall synthesis in response to cell wall damage, particularly in Gram-negative bacteria. Here we describe WigK/WigR, a histidine kinase/response regulator pair that enables Vibrio cholerae, the cholera pathogen, to survive exposure to antibiotics targeting cell wall synthesis in vitro and during infection. Unlike wild-type V. cholerae, mutants lacking wigR fail to recover following exposure to cell-wall-acting antibiotics, and they exhibit a drastically increased cell diameter in the absence of such antibiotics. Conversely, overexpression of wigR leads to cell slimming. Overexpression of activated WigR also results in increased expression of the full set of cell wall synthesis genes and to elevated cell wall content. WigKR-dependent expression of cell wall synthesis genes is induced by various cell-wall-acting antibiotics as well as by overexpression of an endogenous cell wall hydrolase. Thus, WigKR appears to monitor cell wall integrity and to enhance the capacity for increased cell wall production in response to damage. Taken together, these findings implicate WigKR as a regulator of cell wall synthesis that controls cell wall homeostasis in response to antibiotics and likely during normal growth as well.

  • 39. Edlund, T
    et al.
    Ny, Tor
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Rånby, M
    Hedén, L O
    Palm, G
    Holmgren, E
    Josephson, S
    Isolation of cDNA sequences coding for a part of human tissue plasminogen activator.1983In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 80, no 2, p. 349-52Article in journal (Refereed)
    Abstract [en]

    We have isolated a cDNA sequence coding for a part of human tissue plasminogen activator. mRNA coding for tissue plasminogen activator was partially purified, copied into double-stranded cDNA, and cloned into Escherichia coli. Two sets of partially overlapping oligodeoxynucleotide mixtures corresponding to all possible coding sequences for a known portion of the tissue plasminogen activator gene were prepared. One set was used as a probe to screen cDNA containing bacterial clones and both were used as probes in hybridization against purified plasmid DNA. Of 4,200 bacterial clones examined, 1 carried a plasmid that hybridized to both sets of oligonucleotides. This plasmid contained a 370-base-pair cDNA insert, which was shown by nucleotide sequence analysis to code for the cleavage site region in the one-chain form of the human tissue plasminogen activator.

  • 40.
    Ehlers, Ina
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Augusti, Angela
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Betson, Tatiana R.
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Nilsson, Mats B.
    Marshall, John D.
    Schleucher, Juergen
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Detecting long-term metabolic shifts using isotopomers: CO2-driven suppression of photorespiration in C-3 plants over the 20th century2015In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 112, no 51, p. 15585-15590Article in journal (Refereed)
    Abstract [en]

    Terrestrial vegetation currently absorbs approximately a third of anthropogenic CO2 emissions, mitigating the rise of atmospheric CO2. However, terrestrial net primary production is highly sensitive to atmospheric CO2 levels and associated climatic changes. In C-3 plants, which dominate terrestrial vegetation, net photosynthesis depends on the ratio between photorespiration and gross photosynthesis. This metabolic flux ratio depends strongly on CO2 levels, but changes in this ratio over the past CO2 rise have not been analyzed experimentally. Combining CO2 manipulation experiments and deuterium NMR, we first establish that the intramolecular deuterium distribution (deuterium isotopomers) of photosynthetic C-3 glucose contains a signal of the photorespiration/photosynthesis ratio. By tracing this isotopomer signal in herbarium samples of natural C-3 vascular plant species, crops, and a Sphagnum moss species, we detect a consistent reduction in the photorespiration/photosynthesis ratio in response to the similar to 100-ppm CO2 increase between similar to 1900 and 2013. No difference was detected in the isotopomer trends between beet sugar samples covering the 20th century and CO2 manipulation experiments, suggesting that photosynthetic metabolism in sugar beet has not acclimated to increasing CO2 over >100 y. This provides observational evidence that the reduction of the photorespiration/photosynthesis ratio was ca. 25%. The Sphagnum results are consistent with the observed positive correlations between peat accumulation rates and photosynthetic rates over the Northern Hemisphere. Our results establish that isotopomers of plant archives contain metabolic information covering centuries. Our data provide direct quantitative information on the "CO2 fertilization" effect over decades, thus addressing a major uncertainty in Earth system models.

  • 41.
    Elfving, Nils
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Davoine, Céline
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Benlloch, Reyes
    Blomberg, Jeanette
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Brännström, Kristoffer
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Müller, Dörte
    Nilsson, Anders
    Ulfstedt, Mikael
    Ronne, Hans
    Wingsle, Gunnar
    Nilsson, Ove
    Björklund, Stefan
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    The Arabidopsis thaliana Med25 mediator subunit integrates environmental cues to control plant development2011In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 108, no 20, p. 8245-8250Article in journal (Refereed)
    Abstract [en]

    Development in plants is controlled by abiotic environmental cues such as day length, light quality, temperature, drought, and salinity. These signals are sensed by a variety of systems and transmitted by different signal transduction pathways. Ultimately, these pathways are integrated to control expression of specific target genes, which encode proteins that regulate development and differentiation. The molecular mechanisms for such integration have remained elusive. We here show that a linear 130-amino-acids-long sequence in the Med25 subunit of the Arabidopsis thaliana Mediator is a common target for the drought response element binding protein 2A, zinc finger homeodomain 1, and Myb-like transcription factors which are involved in different stress response pathways. In addition, our results show that Med25 together with drought response element binding protein 2A also function in repression of PhyB-mediated light signaling and thus integrate signals from different regulatory pathways.

  • 42.
    Eriksson, Mats
    et al.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Karlsson, Jan
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Ramazanov, Zakir
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Gardeström, Per
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Samuelsson, Göran
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Discovery of an algal mitochondrial carbonic anhydrase: molecular cloning and characterization of a low-CO2-induced polypeptide in Chlamydomonas reinhardtii1996In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 93, no 21, p. 12031-12034Article in journal (Refereed)
    Abstract [en]

    In green unicellular algae, several polypeptides are induced upon exposure to limiting CO2. We report here on the localization and characterization of one of these, a 22-kDa polypeptide in Chlamydomonas reinhardtii. This nuclear-encoded polypeptide is induced in the mitochondria by a lowering of the partial pressure of CO2 in the growth medium from 5% to air CO2 levels. Sequencing of two different cDNA clones coding for the polypeptide identified it as a 20.7-kDa beta-type carbonic anhydrase (CA; carbonate dehydratase, carbonate hydro-lyase, EC 4.2.1.1). The two clones differ in their nucleotide sequences but code for identical proteins, showing that this CA is encoded by at least two genes. Northern blot hybridization reveals that mRNA transcripts are only present in cells transferred to air CO2 levels. A comparison of the deduced amino acid sequence with those of other beta-CAs shows the largest degree of similarity with CA from the cyanobacterium Synechocystis (50% identity and 66% similarity). To our knowledge, this is the first identification and characterization of a mitochondrial CA from a photosynthetic organism.

  • 43. Ertürk-Hasdemir, Deniz
    et al.
    Broemer, Meike
    Leulier, Francois
    Lane, William S
    Paquette, Nicholas
    Hwang, Daye
    Kim, Chan-Hee
    Stöven, Svenja
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Meier, Pascal
    Silverman, Neal
    Two roles for the Drosophila IKK complex in the activation of Relish and the induction of antimicrobial peptide genes2009In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 106, no 24, p. 9779-9784Article in journal (Refereed)
    Abstract [en]

    The Drosophila NF-kappa B transcription factor Relish is an essential regulator of antimicrobial peptide gene induction after Gram-negative bacterial infection. Relish is a bipartite NF-kappa B precursor protein, with an N-terminal Rel homology domain and a C-terminal I kappa B-like domain, similar to mammalian p100 and p105. Unlike these mammalian homologs, Relish is endoproteolytically cleaved after infection, allowing the N-terminal NF-kappa B module to translocate to the nucleus. Signal-dependent activation of Relish, including cleavage, requires both the Drosophila I kappa B kinase (IKK) and death-related ced-3/Nedd2-like protein (DREDD), the Drosophila caspase-8 like protease. In this report, we show that the IKK complex controls Relish by direct phosphorylation on serines 528 and 529. Surprisingly, these phosphorylation sites are not required for Relish cleavage, nuclear translocation, or DNA binding. Instead they are critical for recruitment of RNA polymerase II and antimicrobial peptide gene induction, whereas IKK functions noncatalytically to support Dredd-mediated cleavage of Relish.

  • 44. Evans, Alistair R.
    et al.
    Jones, David
    Boyer, Alison G.
    Brown, James H.
    Costa, Daniel P.
    Ernest, S. K. Morgan
    Fitzgerald, Erich M. G.
    Fortelius, Mikael
    Gittleman, John L.
    Hamilton, Marcus J.
    Harding, Larisa E
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences.
    Lintulaakso, Kari
    Lyons, S. Kathleen
    Okie, Jordan G.
    Saarinen, Juha J.
    Sibly, Richard M.
    Smith, Felisa A.
    Stephens, Patrick R.
    Theodor, Jessica M.
    Uhen, Mark D.
    The maximum rate of mammal evolution2012In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 109, no 11, p. 4187-4190Article in journal (Refereed)
    Abstract [en]

    How fast can a mammal evolve from the size of a mouse to the size of an elephant? Achieving such a large transformation calls for major biological reorganization. Thus, the speed at which this occurs has important implications for extensive faunal changes, including adaptive radiations and recovery from mass extinctions. To quantify the pace of large-scale evolution we developed a metric, clade maximum rate, which represents the maximum evolutionary rate of a trait within a clade. We applied this metric to body mass evolution in mammals over the last 70 million years, during which multiple large evolutionary transitions occurred in oceans and on continents and islands. Our computations suggest that it took a minimum of 1.6, 5.1, and 10 million generations for terrestrial mammal mass to increase 100-, and 1,000-, and 5,000-fold, respectively. Values for whales were down to half the length (i.e., 1.1, 3, and 5 million generations), perhaps due to the reduced mechanical constraints of living in an aquatic environment. When differences in generation time are considered, we find an exponential increase in maximum mammal body mass during the 35 million years following the Cretaceous-Paleogene (K-Pg) extinction event. Our results also indicate a basic asymmetry in macroevolution: very large decreases (such as extreme insular dwarfism) can happen at more than 10 times the rate of increases. Our findings allow more rigorous comparisons of microevolutionary and macroevolutionary patterns and processes.

  • 45. Fadeev, Andrey
    et al.
    Mendoza-Garcia, Patricia
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Irion, Uwe
    Guan, Jikui
    Pfeifer, Kathrin
    Wiessner, Stephanie
    Serluca, Fabrizio
    Singh, Ajeet Pratap
    Nuesslein-Volhard, Christiane
    Palmer, Ruth H.
    ALKALs are in vivo ligands for ALK family receptor tyrosine kinases in the neural crest and derived cells2018In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 115, no 4, p. E630-E638Article in journal (Refereed)
    Abstract [en]

    Mutations in anaplastic lymphoma kinase (ALK) are implicated in somatic and familial neuroblastoma, a pediatric tumor of neural crest-derived tissues. Recently, biochemical analyses have identified secreted small ALKAL proteins (FAM150, AUG) as potential ligands for human ALK and the related leukocyte tyrosine kinase (LTK). In the zebrafish Danio rerio, DrLtk, which is similar to human ALK in sequence and domain structure, controls the development of iridophores, neural crest-derived pigment cells. Hence, the zebrafish system allows studying Alk/Ltk and Alkals involvement in neural crest regulation in vivo. Using zebrafish pigment pattern formation, Drosophila eye patterning, and cell culture-based assays, we show that zebrafish Alkals potently activate zebrafish Ltk and human ALK driving downstream signaling events. Overexpression of the three DrAlkals cause ectopic iridophore development, whereas loss-of-function alleles lead to spatially distinct patterns of iridophore loss in zebrafish larvae and adults. alkal loss-of-function triple mutants completely lack iridophores and are larval lethal as is the case for ltk null mutants. Our results provide in vivo evidence of (i) activation of ALK/LTK family receptors by ALKALs and (ii) an involvement of these ligand-receptor complexes in neural crest development.

  • 46. Fagard, M
    et al.
    Boutet, S
    Morel, J B
    Bellini, C
    Vaucheret, H
    AGO1, QDE-2, and RDE-1 are related proteins required for post-transcriptional gene silencing in plants, quelling in fungi, and RNA interference in animals.2000In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 97, no 21Article in journal (Refereed)
    Abstract [en]

    Introduction of transgene DNA may lead to specific degradation of RNAs that are homologous to the transgene transcribed sequence through phenomena named post-transcriptional gene silencing (PTGS) in plants, quelling in fungi, and RNA interference (RNAi) in animals. It was shown previously that PTGS, quelling, and RNAi require a set of related proteins (SGS2, QDE-1, and EGO-1, respectively). Here we report the isolation of Arabidopsis mutants impaired in PTGS which are affected at the Argonaute1 (AGO1) locus. AGO1 is similar to QDE-2 required for quelling and RDE-1 required for RNAi. Sequencing of ago1 mutants revealed one amino acid essential for PTGS that is also present in QDE-2 and RDE-1 in a highly conserved motif. Taken together, these results confirm the hypothesis that these processes derive from a common ancestral mechanism that controls expression of invading nucleic acid molecules at the post-transcriptional level. As opposed to rde-1 and qde-2 mutants, which are viable, ago1 mutants display several developmental abnormalities, including sterility. These results raise the possibility that PTGS, or at least some of its elements, could participate in the regulation of gene expression during development in plants.

  • 47. Falster, Daniel S.
    et al.
    Brännström, Åke
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics. Evolution and Ecology Program, International Institute for Applied Systems Analysis, A-2361 Laxenburg, Austria.
    Westoby, Mark
    Dieckmann, Ulf
    Multitrait successional forest dynamics enable diverse competitive coexistence2017In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 114, no 13, p. E2719-E2728Article in journal (Refereed)
    Abstract [en]

    To explain diversity in forests, niche theory must show how multiple plant species coexist while competing for the same resources. Although successional processes are widespread in forests, theoretical work has suggested that differentiation in successional strategy allows only a few species stably to coexist, including only a single shade tolerant. However, this conclusion is based on current niche models, which encode a very simplified view of plant communities, suggesting that the potential for niche differentiation has remained unexplored. Here, we show how extending successional niche models to include features common to all vegetation-height-structured competition for light under a prevailing disturbance regime and two trait-mediated tradeoffs in plant function-enhances the diversity of species that can be maintained, including a diversity of shade tolerants. We identify two distinct axes of potential niche differentiation, corresponding to the traits leaf mass per unit leaf area and height at maturation. The first axis allows for coexistence of different shade tolerances and the second axis for coexistence among species with the same shade tolerance. Addition of this second axis leads to communities with a high diversity of shade tolerants. Niche differentiation along the second axis also generates regions of trait space wherein fitness is almost equalized, an outcome we term "evolutionarily emergent near-neutrality." For different environmental conditions, our model predicts diverse vegetation types and trait mixtures, akin to observations. These results indicate that the outcomes of successional niche differentiation are richer than previously thought and potentially account for mixtures of traits and species observed in forests worldwide.

  • 48. Forbes, Bruce C
    et al.
    Stammler, Florian
    Kumpula, Timo
    Meschtyb, Nina
    Pajunen, Anu
    Kaarlejärvi, Elina
    Umeå University, Faculty of Science and Technology, Ecology and Environmental Science.
    High resilience in the Yamal-Nenets social–ecological system, West Siberian Arctic, Russia2009In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 106, no 52, p. 22041-22048Article in journal (Refereed)
    Abstract [en]

    Tundra ecosystems are vulnerable to hydrocarbon development, in part because small-scale, low-intensity disturbances can affect vegetation, permafrost soils, and wildlife out of proportion to their spatial extent. Scaling up to include human residents, tightly integrated arctic social-ecological systems (SESs) are believed similarly susceptible to industrial impacts and climate change. In contrast to northern Alaska and Canada, most terrestrial and aquatic components of West Siberian oil and gas fields are seasonally exploited by migratory herders, hunters, fishers, and domesticated reindeer (Rangifer tarandus L.). Despite anthropogenic fragmentation and transformation of a large proportion of the environment, recent socioeconomic upheaval, and pronounced climate warming, we find the Yamal-Nenets SES highly resilient according to a few key measures. We detail the remarkable extent to which the system has successfully reorganized in response to recent shocks and evaluate the limits of the system's capacity to respond. Our analytical approach combines quantitative methods with participant observation to understand the overall effects of rapid land use and climate change at the level of the entire Yamal system, detect thresholds crossed using surrogates, and identify potential traps. Institutional constraints and drivers were as important as the documented ecological changes. Particularly crucial to success is the unfettered movement of people and animals in space and time, which allows them to alternately avoid or exploit a wide range of natural and anthropogenic habitats. However, expansion of infrastructure, concomitant terrestrial and freshwater ecosystem degradation, climate change, and a massive influx of workers underway present a looming threat to future resilience.

  • 49. Fuchino, Katsuya
    et al.
    Bagchi, Sonchita
    Cantlay, Stuart
    Sandblad, Linda
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Wu, Di
    Bergman, Jessica
    Kamali-Moghaddam, Masood
    Flardh, Klas
    Ausmees, Nora
    Dynamic gradients of an intermediate filament-like cytoskeleton are recruited by a polarity landmark during apical growth2013In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 110, no 21, p. E1889-E1897Article in journal (Refereed)
    Abstract [en]

    Intermediate filament (IF)-like cytoskeleton emerges as a versatile tool for cellular organization in all kingdoms of life, underscoring the importance of mechanistically understanding its diverse manifestations. We showed previously that, in Streptomyces (a bacterium with a mycelial lifestyle similar to that of filamentous fungi, including extreme cell and growth polarity), the IF protein FilP confers rigidity to the hyphae by an unknown mechanism. Here, we provide a possible explanation for the IF-like function of FilP by demonstrating its ability to self-assemble into a cis-interconnected regular network in vitro and its localization into structures consistent with a cytoskeletal network in vivo. Furthermore, we reveal that a spatially restricted interaction between FilP and DivIVA, the main component of the Streptomyces polarisome complex, leads to formation of apical gradients of FilP in hyphae undergoing active tip extension. We propose that the coupling between the mechanism driving polar growth and the assembly of an IF cytoskeleton provides each new hypha with an additional stress-bearing structure at its tip, where the nascent cell wall is inevitably more flexible and compliant while it is being assembled and matured. Our data suggest that recruitment of cytoskeleton around a cell polarity landmark is a broadly conserved strategy in tip-growing cells.

  • 50. Fuchs, I
    et al.
    Philippar, K
    Ljung, K
    Sandberg, G
    Hedrich, R
    Blue light regulates an auxin-induced K+-channel gene in the maize coleoptile2003In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 100, no 20, p. 11795-11800Article in journal (Refereed)
    Abstract [en]

    Auxin redistribution along gravistimulated maize coleoptiles causes differential expression of the auxin-induced K+-channel gene ZMK1 (Zea mays K+ channel 1) and precedes the curvature response. To evaluate the role of ZMK1 during phototropism, we here investigated blue light-stimulated coleoptiles. Four hours of blue light stimulation resulted in phototropic bending (23degrees). Rotation on a clinostat, at nominally "zero" gravity, and simultaneous stimulation with unidirectional blue light, however, resulted in up to 510 bending toward the light. Differential ZMK1 transcription reached a maximum after 90 min of blue light stimulation under gravity, whereas ZMK1 expression remained asymmetric for at least 180 min in photostimulated coleoptiles on a clinostat. We therefore conclude that the stronger phototropic bending under nominally "zero" gravity results from prolonged differential expression of ZMK1. Under both conditions, asymmetric expression of ZMK1 could be superimposed on the lateral auxin gradient across the coleoptile tip, whereas the gene for the blue light receptor phototropin 1 (PHOT1), expressed in the tip only, was not differentially regulated in response to blue light. The activation of the two different receptors eliciting the photo- and gravitropic response of the coleoptile thus feeds into a common signaling pathway, resulting in auxin redistribution in the coleoptile tip and finally in differential transcription of ZMK1. In the process of signal integration, gravity transduction restricts the magnitude of the blue light-inducible ZMK1 gradient. The spatial and temporal distribution of ZMK1 transcripts and thus differential K+ uptake in both flanks of the coleoptile seem to limit the stimulus-induced bending of this sensory organ.

1234 1 - 50 of 156
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf