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  • 1.
    Abelein, Axel
    et al.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Gräslund, Astrid
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Danielsson, Jens
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Zinc as chaperone-mimicking agent for retardation of amyloid beta peptide fibril formation2015In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 112, no 17, 5407-5412 p.Article in journal (Refereed)
    Abstract [en]

    Metal ions have emerged to play a key role in the aggregation process of amyloid beta (A beta) peptide that is closely related to the pathogenesis of Alzheimer's disease. A detailed understanding of the underlying mechanistic process of peptide-metal interactions, however, has been challenging to obtain. By applying a combination of NMR relaxation dispersion and fluorescence kinetics methods we have investigated quantitatively the thermodynamic A beta-Zn2+ binding features as well as how Zn2+ modulates the nucleation mechanism of the aggregation process. Our results show that, under near-physiological conditions, substoichiometric amounts of Zn2+ effectively retard the generation of amyloid fibrils. A global kinetic profile analysis reveals that in the absence of zinc A beta(40) aggregation is driven by a monomer-dependent secondary nucleation process in addition to fibril-end elongation. In the presence of Zn2+, the elongation rate is reduced, resulting in reduction of the aggregation rate, but not a complete inhibition of amyloid formation. We show that Zn2+ transiently binds to residues in the N terminus of the monomeric peptide. A thermodynamic analysis supports a model where the N terminus is folded around the Zn2+ ion, forming a marginally stable, short-lived folded A beta(40) species. This conformation is highly dynamic and only a few percent of the peptide molecules adopt this structure at any given time point. Our findings suggest that the folded A beta(40)-Zn2+ complex modulates the fibril ends, where elongation takes place, which efficiently retards fibril formation. In this conceptual framework we propose that zinc adopts the role of a minimal antiaggregation chaperone for A beta(40).

  • 2.
    Acerbi, Alberto
    et al.
    Department of Psychology, University of Bologna.
    Enquist, Magnus
    Stockholm University, Faculty of Humanities, Centre for the Study of Cultural Evolution. Stockholm University, Faculty of Science, Department of Zoology, Department of Ethology.
    Ghirlanda, Stefano
    Stockholm University, Faculty of Humanities, Centre for the Study of Cultural Evolution.
    Cultural evolution and individual development of openness and conservatism2009In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, Vol. 106, no 45, 18931-18935 p.Article in journal (Refereed)
    Abstract [en]

    We present a model of cultural evolution in which an individual's propensity to engage in social learning is affected by social learning itself. We assume that individuals observe cultural traits displayed by others and decide whether to copy them based on their overall preference for the displayed traits. Preferences, too, can be transmitted between individuals. Our results show that such cultural dynamics tends to produce conservative individuals, i.e., individuals who are reluctant to copy new traits. Openness to new information, however, can be maintained when individuals need significant time to acquire the cultural traits that make them effective cultural models. We show that a gradual enculturation of young individuals by many models and a larger cultural repertoire to be acquired are favorable circumstances for the long-term maintenance of openness in individuals and groups. Our results agree with data about lifetime personality change, showing that openness to new information decreases with age. Our results show that cultural remodeling of cultural transmission is a powerful force in cultural evolution, i.e., that cultural evolution can change its own dynamics

  • 3. Ahn, Young O.
    et al.
    Mahinthichaichan, Paween
    Lee, Hyun Ju
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Ouyang, Hanlin
    Kaluka, Daniel
    Yeh, Syun-Ru
    Arjona, Davinia
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Rousseau, Denis L.
    Tajkhorshid, Emad
    Ädelroth, Pia
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Gennis, Robert B.
    Conformational coupling between the active site and residues within the K-C-channel of the Vibrio cholerae cbb(3)-type (C-family) oxygen reductase2014In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 111, no 42, E4419-E4428 p.Article in journal (Refereed)
    Abstract [en]

    The respiratory chains of nearly all aerobic organisms are terminated by proton-pumping heme-copper oxygen reductases (HCOs). Previous studies have established that C-family HCOs contain a single channel for uptake from the bacterial cytoplasm of all chemical and pumped protons, and that the entrance of the K-C-channel is a conserved glutamate in subunit III. However, the majority of the K-C-channel is within subunit I, and the pathway from this conserved glutamate to subunit I is not evident. In the present study, molecular dynamics simulations were used to characterize a chain of water molecules leading from the cytoplasmic solution, passing the conserved glutamate in subunit III and extending into subunit I. Formation of the water chain, which controls the delivery of protons to the K-C-channel, was found to depend on the conformation of Y241(Vc), located in subunit I at the interface with subunit III. Mutations of Y241(Vc) (to A/F/H/S) in the Vibrio cholerae cbb(3) eliminate catalytic activity, but also cause perturbations that propagate over a 28-angstrom distance to the active site heme b(3). The data suggest a linkage between residues lining the KC-channel and the active site of the enzyme, possibly mediated by transmembrane helix alpha 7, which contains both Y241(Vc) and the active site crosslinked Y255(Vc), as well as two Cu-B histidine ligands. Other mutations of residues within or near helix alpha 7 also perturb the active site, indicating that this helix is involved in modulation of the active site of the enzyme.

  • 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
    Gloeckner, Carina
    Echols, Nathaniel
    Sierra, Raymond G.
    Schafer, Donald W.
    Sellberg, Jonas
    Stockholm University, Faculty of Science, Department of Physics.
    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, Sebastien
    Williams, Garth J.
    Zouni, Athina
    Messinger, Johannes
    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, 19103-19107 p.Article 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. K beta(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. Antonelli, A
    et al.
    Nylander, Johan
    Stockholm University, Faculty of Science, Department of Botany.
    Persson, C
    Sanmartín, I
    Tracing the impact of the Andean uplift on Neotropical plant evolution: evidence from the coffee family2009In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 106, no 24, 9749-9754 p.Article in journal (Refereed)
    Abstract [en]

    Recent phylogenetic studies have revealed the major role played by the uplift of the Andes in the extraordinary diversification of the Neotropical flora. These studies, however, have typically considered the Andean uplift as a single, time-limited event fostering the evolution of highland elements. This contrasts with geological reconstructions indicating that the uplift occurred in discrete periods from west to east and that it affected different regions at different times. We introduce an approach for integrating Andean tectonics with biogeographic reconstructions of Neotropical plants, using the coffee family (Rubiaceae) as a model group. The distribution of this family spans highland and montane habitats as well as tropical lowlands of Central and South America, thus offering a unique opportunity to study the influence of the Andean uplift on the entire Neotropical flora. Our results suggest that the Rubiaceae originated in the Paleotropics and used the boreotropical connection to reach South America. The biogeographic patterns found corroborate the existence of a long-lasting dispersal barrier between the Northern and Central Andes, the "Western Andean Portal.'' The uplift of the Eastern Cordillera ended this barrier, allowing dispersal of boreotropical lineages to the South, but gave rise to a huge wetland system ("Lake Pebas'') in western Amazonia that prevented in situ speciation and floristic dispersal between the Andes and Amazonia for at least 6 million years. Here, we provide evidence of these events in plants

  • 6. Aze, T.
    et al.
    - Ezard, T. H. G.
    Purvis, A.
    Coxall, Helen
    Stockholm University, Faculty of Science, Department of Geological Sciences.
    Stewart, D. R. M.
    Wade, B. S.
    Pearson, P. N.
    Identifying anagenesis cladogenesis in the fossil record2013In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 110, no 32, E2946- p.Article in journal (Refereed)
  • 7.
    Balk, Lennart
    et al.
    Stockholm University, Faculty of Science, Department of Applied Environmental Science (ITM).
    Hägerroth, Per-Ake
    Stockholm University, Faculty of Science, Department of Applied Environmental Science (ITM).
    Åkerman, Gun
    Stockholm University, Faculty of Science, Department of Applied Environmental Science (ITM).
    Hanson, Marsha
    Stockholm University, Faculty of Science, Department of Applied Environmental Science (ITM).
    Tjärnlund, Ulla
    Stockholm University, Faculty of Science, Department of Applied Environmental Science (ITM).
    Hansson, Tomas
    Stockholm University, Faculty of Science, Department of Applied Environmental Science (ITM).
    Hallgrimsson, Gunnar Thor
    Zebühr, Yngve
    Stockholm University, Faculty of Science, Department of Applied Environmental Science (ITM).
    Broman, Dag
    Stockholm University, Faculty of Science, Department of Applied Environmental Science (ITM).
    Mörner, Torsten
    Sundberg, Henrik
    Wild birds of declining European species are dying from a thiamine deficiency syndrome.2009In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 106, no 29, 12001-12006 p.Article in journal (Refereed)
    Abstract [en]

    Wild birds of several species are dying in large numbers from an idiopathic paralytic disease in the Baltic Sea area. Here, we demonstrate strong relationships between this disease, breeding failure, and thiamine (vitamin B(1)) deficiency in eggs, pulli, and full-grown individuals. Thiamine is essential for vertebrates, and its diphosphorylated form functions as a cofactor for several life sustaining enzymes, whereas the triphosphorylated form is necessary for the functioning of neuronal membranes. Paralyzed individuals were remedied by thiamine treatment. Moreover, thiamine deficiency and detrimental effects on thiamine-dependent enzymes were demonstrated in the yolk, liver, and brain. We propose that the mortality and breeding failure are part of a thiamine deficiency syndrome, which may have contributed significantly to declines in many bird populations during the last decades.

  • 8. Bergh, Johan
    et al.
    Zetterstrom, Per
    Andersen, Peter M.
    Brannstrom, Thomas
    Graffmo, Karin S.
    Jonsson, P. Andreas
    Lang, Lisa
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Danielsson, Jens
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Oliveberg, Mikael
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Marklund, Stefan L.
    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, 4489-4494 p.Article 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.

  • 9.
    Bernsel, Andreas
    et al.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Viklund, Håkan
    Falk, Jenny
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Lindahl, Erik
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    von Heijne, Gunnar
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Elofsson, Arne
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Prediction of membrane-protein topology from first principles2008In: Proceedings of the National Academy of Science of the United States of America, ISSN 0027-8424, Vol. 105, no 20, 7177-7181 p.Article in journal (Refereed)
  • 10. Berrah, Nora
    et al.
    Fang, Li
    Murphy, Brendan
    Osipov, Timur
    Ueda, Kiyoshi
    Kukk, Edwin
    Feifel, Raimund
    van der Meulen, Peter
    Stockholm University, Faculty of Science, Department of Physics.
    Salén, Peter
    Stockholm University, Faculty of Science, Department of Physics.
    Schmidt, Henning T.
    Stockholm University, Faculty of Science, Department of Physics.
    Thomas, Richard D.
    Stockholm University, Faculty of Science, Department of Physics.
    Larsson, Mats
    Stockholm University, Faculty of Science, Department of Physics.
    Richter, Robert
    Prince, Kevin C.
    Bozek, John D.
    Bostedt, Christoph
    Wada, Shin-ichi
    Piancastelli, Maria N.
    Tashiro, Motomichi
    Ehara, Masahiro
    Double-core-hole spectroscopy for chemical analysis with an intense X-ray femtosecond laser2011In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 108, no 41, 16912-16915 p.Article in journal (Refereed)
    Abstract [en]

    Theory predicts that double-core-hole (DCH) spectroscopy can provide a new powerful means of differentiating between similar chemical systems with a sensitivity not hitherto possible. Although DCH ionization on a single site in molecules was recently measured with double-and single-photon absorption, double-core holes with single vacancies on two different sites, allowing unambiguous chemical analysis, have remained elusive. Here we report that direct observation of double-core holes with single vacancies on two different sites produced via sequential two-photon absorption, using short, intense X-ray pulses from the Linac Coherent Light Source free-electron laser and compare it with theoretical modeling. The observation of DCH states, which exhibit a unique signature, and agreement with theory proves the feasibility of the method. Our findings exploit the ultrashort pulse duration of the free-electron laser to eject two core electrons on a time scale comparable to that of Auger decay and demonstrate possible future X-ray control of physical inner-shell processes.

  • 11.
    Berry, Bruce W.
    et al.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. University of Pennsylvania, USA.
    Martinez-Rivera, Melissa C.
    Tommos, Cecilia
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. University of Pennsylvania, USA.
    Reversible voltammograms and a Pourbaix diagram for a protein tyrosine radical2012In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 109, no 25, 9739-9743 p.Article in journal (Refereed)
    Abstract [en]

    Reversible voltammograms and a voltammetry half-wave potential versus solution pH diagram are described for a protein tyrosine radical. This work required a de novo designed tyrosine-radical protein displaying a unique combination of structural and electrochemical properties. The alpha Y-3 protein is structurally stable across a broad pH range. The redox-active tyrosine Y32 resides in a desolvated and well-structured environment. Y32 gives rise to reversible square-wave and differential pulse voltammograms at alkaline pH. The formal potential of the Y32-O-center dot/Y32-OH redox couple is determined to 918 +/- 2 mV versus the normal hydrogen electrode at pH 8.40 +/- 0.01. The observation that Y32 gives rise to fully reversible voltammograms translates into an estimated lifetime of >= 30 ms for the Y32-O-center dot state. This illustrates the range of tyrosine-radical stabilization that a structured protein can offer. Y32 gives rise to quasireversible square-wave and differential pulse voltammograms at acidic pH. These voltammograms represent the Y32 species at the upper edge of the quasirevesible range. The square-wave net potential closely approximates the formal potential of the Y32-O center dot/Y32-OH redox couple to 1,070 +/- 1 mV versus the normal hydrogen electrode at pH 5.52 +/- 0.01. The differential pulse voltammetry half-wave potential of the Y32-O-center dot/Y32-OH redox pair is measured between pH 4.7 and 9.0. These results are described and analyzed.

  • 12.
    Berthold, Catrine L.
    et al.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Wang, He
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Nordlund, Stefan
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Högbom, Martin
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Mechanism of ADP-ribosylation removal revealed by the structure and ligand complexes of the dimanganese mono-ADP-ribosylhydrolase DraG2009In: Proceedings of the National Academy of Science of the United States of America, ISSN 0027-8424, Vol. 106, no 34, 14247-14252 p.Article in journal (Refereed)
    Abstract [en]

    ADP-ribosylation is a ubiquitous regulatory posttranslational modification involved in numerous key processes such as DNA repair, transcription, cell differentiation, apoptosis, and the pathogenic mechanism of certain bacterial toxins. Despite the importance of this reversible process, very little is known about the structure and mechanism of the hydrolases that catalyze removal of the ADP-ribose moiety. In the phototrophic bacterium Rhodospirillum rubrum, dinitrogenase reductase-activating glycohydrolase (DraG), a dimanganese enzyme that reversibly associates with the cell membrane, is a key player in the regulation of nitrogenase activity. DraG has long served as a model protein for ADP-ribosylhydrolases. Here, we present the crystal structure of DraG in the holo and ADP-ribose bound forms. We also present the structure of a reaction intermediate analogue and propose a detailed catalytic mechanism for protein de-ADP-ribosylation involving ring opening of the substrate ribose. In addition, the particular manganese coordination in DraG suggests a rationale for the enzyme's preference for manganese over magnesium, although not requiring a redox active metal for the reaction.

  • 13.
    Boija, Ann
    et al.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Mannervik, Mattias
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Initiation of diverse epigenetic states during nuclear programming of the Drosophila body plan2016In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 113, no 31, 8735-8740 p.Article in journal (Refereed)
    Abstract [en]

    Epigenetic patterns of histone modifications contribute to the maintenance of tissue-specific gene expression. Here, we show that such modifications also accompany the specification of cell identities by the NF-kappa B transcription factor Dorsal in the precellular Drosophila embryo. We provide evidence that the maternal pioneer factor, Zelda, is responsible for establishing poised RNA polymerase at Dorsal target genes before Dorsal-mediated zygotic activation. At the onset of cell specification, Dorsal recruits the CBP/p300 coactivator to the regulatory regions of defined target genes in the presumptive neuroectoderm, resulting in their histone acetylation and transcriptional activation. These genes are inactive in the mesoderm due to transcriptional quenching by the Snail repressor, which precludes recruitment of CBP and prevents histone acetylation. By contrast, inactivation of the same enhancers in the dorsal ectoderm is associated with Polycomb-repressed H3K27me3 chromatin. Thus, the Dorsal morphogen gradient produces three distinct histone signatures including two modes of transcriptional repression, active repression (hypoacetylation), and inactivity (H3K27me3). Whereas histone hypoacetylation is associated with a poised polymerase, H3K27me3 displaces polymerase from chromatin. Our results link different modes of RNA polymerase regulation to separate epigenetic patterns and demonstrate that developmental determinants orchestrate differential chromatin states, providing new insights into the link between epigenetics and developmental patterning.

  • 14. Brace, Selina
    et al.
    Palkopoulou, Eleftheria
    Stockholm University, Faculty of Science, Department of Zoology. Swedish Museum of National History, Sweden.
    Dalén, Love
    Lister, Adrian M.
    Miller, Rebecca
    Otte, Marcel
    Germonpre, Mietje
    Blockley, Simon P. E.
    Stewart, John R.
    Barnes, Ian
    Serial population extinctions in a small mammal indicate Late Pleistocene ecosystem instability2012In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 109, no 50, 20532-20536 p.Article in journal (Refereed)
    Abstract [en]

    The Late Pleistocene global extinction of many terrestrial mammal species has been a subject of intensive scientific study for over a century, yet the relative contributions of environmental changes and the global expansion of humans remain unresolved. A defining component of these extinctions is a bias toward large species, with the majority of small-mammal taxa apparently surviving into the present. Here, we investigate the population-level history of a key tundra-specialist small mammal, the collared lemming (Dicrostonyx torquatus), to explore whether events during the Late Pleistocene had a discernible effect beyond the large mammal fauna. Using ancient DNA techniques to sample across three sites in North-West Europe, we observe a dramatic reduction in genetic diversity in this species over the last 50,000 y. We further identify a series of extinction-recolonization events, indicating a previously unrecognized instability in Late Pleistocene small-mammal populations, which we link with climatic fluctuations. Our results reveal climate-associated, repeated regional extinctions in a keystone prey species across the Late Pleistocene, a pattern likely to have had an impact on the wider steppe-tundra community, and one that is concordant with environmental change as a major force in structuring Late Pleistocene biodiversity.

  • 15. Brand, Stephen K.
    et al.
    Schmidt, Joel E.
    Deem, Michael W.
    Daeyaert, Frits
    Ma, Yanhang
    Terasaki, Osamu
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK). ShanghaiTech University, China.
    Orazov, Marat
    Davis, Mark E.
    Enantiomerically enriched, polycrystalline molecular sieves2017In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 114, no 20, 5101-5106 p.Article in journal (Refereed)
    Abstract [en]

    Zeolite and zeolite-like molecular sieves are being used in a large number of applications such as adsorption and catalysis. Achievement of the long-standing goal of creating a chiral, polycrystalline molecular sieve with bulk enantioenrichment would enable these materials to perform enantioselective functions. Here, we report the synthesis of enantiomerically enriched samples of a molecular sieve. Enantiopure organic structure directing agents are designed with the assistance of computational methods and used to synthesize enantioenriched, polycrystalline molecular sieve samples of either enantiomer. Computational results correctly predicted which enantiomer is obtained, and enantiomeric enrichment is proven by high-resolution transmission electron microscopy. The enantioenriched and racemic samples of the molecular sieves are tested as adsorbents and heterogeneous catalysts. The enantioenriched molecular sieves show enantioselectivity for the ring opening reaction of epoxides and enantioselective adsorption of 2-butanol (the R enantiomer of the molecular sieve shows opposite and approximately equal enantioselectivity compared with the S enantiomer of the molecular sieve, whereas the racemic sample of the molecular sieve shows no enantioselectivity).

  • 16. Braun, Tatjana
    et al.
    Orlova, Albina
    Valegård, Karin
    Lindås, Ann-Christin
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Schröder, Gunnar F.
    Egelman, Edward H.
    Archaeal actin from a hyperthermophile forms a single-stranded filament2015In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 112, no 30, 9340-9345 p.Article in journal (Refereed)
    Abstract [en]

    The prokaryotic origins of the actin cytoskeleton have been firmly established, but it has become clear that the bacterial actins form a wide variety of different filaments, different both from each other and from eukaryotic F-actin. We have used electron cryomicroscopy (cryo-EM) to examine the filaments formed by the protein crenactin (a crenarchaeal actin) from Pyrobaculum calidifontis, an organism that grows optimally at 90 degrees C. Although this protein only has similar to 20% sequence identity with eukaryotic actin, phylogenetic analyses have placed it much closer to eukaryotic actin than any of the bacterial homologs. It has been assumed that the crenactin filament is double-stranded, like F-actin, in part because it would be hard to imagine how a single-stranded filament would be stable at such high temperatures. We show that not only is the crenactin filament single-stranded, but that it is remarkably similar to each of the two strands in F-actin. A large insertion in the crenactin sequence would prevent the formation of an F-actin-like double-stranded filament. Further, analysis of two existing crystal structures reveals six different subunit-subunit interfaces that are filament-like, but each is different from the others in terms of significant rotations. This variability in the subunit-subunit interface, seen at atomic resolution in crystals, can explain the large variability in the crenactin filaments observed by cryo-EM and helps to explain the variability in twist that has been observed for eukaryotic actin filaments.

  • 17.
    Caballero, Rodrigo
    et al.
    Stockholm University, Faculty of Science, Department of Meteorology .
    Huber, Matthew
    State-dependent climate sensitivity in past warm climates and its implications for future climate projections2013In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 110, no 35, 14162-14167 p.Article in journal (Refereed)
    Abstract [en]

    Projections of future climate depend critically on refined estimates of climate sensitivity. Recent progress in temperature proxies dramatically increases the magnitude of warming reconstructed from early Paleogene greenhouse climates and demands a close examination of the forcing and feedback mechanisms that maintained this warmth and the broad dynamic range that these paleoclimate records attest to. Here, we show that several complementary resolutions to these questions are possible in the context of model simulations using modern and early Paleogene configurations. We find that (i) changes in boundary conditions representative of slow Earth system feedbacks play an important role in maintaining elevated early Paleogene temperatures, (ii) radiative forcing by carbon dioxide deviates significantly from pure logarithmic behavior at concentrations relevant for simulation of the early Paleogene, and (iii) fast or Charney climate sensitivity in this model increases sharply as the climate warms. Thus, increased forcing and increased slow and fast sensitivity can all play a substantial role in maintaining early Paleogene warmth. This poses an equifinality problem: The same climate can be maintained by a different mix of these ingredients; however, at present, the mix cannot be constrained directly from climate proxy data. The implications of strongly state-dependent fast sensitivity reach far beyond the early Paleogene. The study of past warm climates may not narrow uncertainty in future climate projections in coming centuries because fast climate sensitivity may itself be state-dependent, but proxies and models are both consistent with significant increases in fast sensitivity with increasing temperature.

  • 18.
    Carlberg, Inger
    et al.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Hansson, Maria
    Kieselbach, Thomas
    Schröder, Wolfgang P
    Andersson, Bertil
    Vener, Alexander V
    A novel plant protein undergoing light-induced phosphorylation and release from the photosynthetic thylakoid membranes2003In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 100, no 2, 757-62 p.Article in journal (Refereed)
    Abstract [en]

    The characteristics of a phosphoprotein with a relative electrophoretic mobility of 12 kDa have been unknown during two decades of studies on redox-dependent protein phosphorylation in plant photosynthetic membranes. Digestion of this protein from spinach thylakoid membranes with trypsin and subsequent tandem nanospray-quadrupole-time-of-flight mass spectrometry of the peptides revealed a protein sequence that did not correspond to any previously known protein. Sequencing of the corresponding cDNA uncovered a gene for a precursor protein with a transit peptide followed by a strongly basic mature protein with a molecular mass of 8,640 Da. Genes encoding homologous proteins were found on chromosome 3 of Arabidopsis and rice as well as in ESTs from 20 different plant species, but not from any other organisms. The protein can be released from the membrane with high salt and is also partially released in response to light-induced phosphorylation of thylakoids, in contrast to all other known thylakoid phosphoproteins, which are integral to the membrane. On the basis of its properties, this plant-specific protein is named thylakoid soluble phosphoprotein of 9 kDa (TSP9). Mass spectrometric analyses revealed the existence of non-, mono-, di-, and triphosphorylated forms of TSP9 and phosphorylation of three distinct threonine residues in the central part of the protein. The phosphorylation and release of TSP9 from the photosynthetic membrane on illumination favor participation of this basic protein in cell signaling and regulation of plant gene expression in response to changing light conditions.

  • 19. Carpenter, Stephen R.
    et al.
    Brock, William A.
    Folke, Carl
    Stockholm University, Faculty of Science, Stockholm Resilience Centre. Royal Swedish Academy of Sciences, Sweden.
    van Nes, Egbert H.
    Scheffer, Marten
    Allowing variance may enlarge the safe operating space for exploited ecosystems2015In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 112, no 46, 14384-14389 p.Article in journal (Refereed)
    Abstract [en]

    Variable flows of food, water, or other ecosystem services complicate planning. Management strategies that decrease variability and increase predictability may therefore be preferred. However, actions to decrease variance over short timescales (2-4 y), when applied continuously, may lead to long-term ecosystem changes with adverse consequences. We investigated the effects of managing short-term variance in three well-understood models of ecosystem services: lake eutrophication, harvest of a wild population, and yield of domestic herbivores on a rangeland. In all cases, actions to decrease variance can increase the risk of crossing critical ecosystem thresholds, resulting in less desirable ecosystem states. Managing to decrease short-term variance creates ecosystem fragility by changing the boundaries of safe operating spaces, suppressing information needed for adaptive management, cancelling signals of declining resilience, and removing pressures that may build tolerance of stress. Thus, the management of variance interacts strongly and inseparably with the management of resilience. By allowing for variation, learning, and flexibility while observing change, managers can detect opportunities and problems as they develop while sustaining the capacity to deal with them.

  • 20. Carstensen, Jacob
    et al.
    Andersen, Jesper H.
    Gustafsson, Bo G.
    Stockholm University, Faculty of Science, Stockholm University Baltic Sea Centre, Baltic Nest Institute.
    Conley, Daniel J.
    Deoxygenation of the Baltic Sea during the last century2014In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 111, no 15, 5628-5633 p.Article in journal (Refereed)
    Abstract [en]

    Deoxygenation is a global problem in coastal and open regions of the ocean, and has led to expanding areas of oxygen minimum zones and coastal hypoxia. The recent expansion of hypoxia in coastal ecosystems has been primarily attributed to global warming and enhanced nutrient input from land and atmosphere. The largest anthropogenically induced hypoxic area in the world is the Baltic Sea, where the relative importance of physical forcing versus eutrophication is still debated. We have analyzed water column oxygen and salinity profiles to reconstruct oxygen and stratification conditions over the last 115 y and compare the influence of both climate and anthropogenic forcing on hypoxia. We report a 10-fold increase of hypoxia in the Baltic Sea and show that this is primarily linked to increased inputs of nutrients from land, although increased respiration from higher temperatures during the last two decades has contributed to worsening oxygen conditions. Although shifts in climate and physical circulation are important factors modulating the extent of hypoxia, further nutrient reductions in the Baltic Sea will be necessary to reduce the ecosystems impacts of deoxygenation.

  • 21.
    Carter, Sidney D.
    et al.
    Stockholm University, Faculty of Science, The Wenner-Gren Institute .
    Vigasova, Dana
    Chen, Jiang
    Stockholm University, Faculty of Science, The Wenner-Gren Institute .
    Chovanec, Miroslav
    Åström, Stefan U.
    Stockholm University, Faculty of Science, The Wenner-Gren Institute .
    Nej1 recruits the Srs2 helicase to DNA double-strand breaks and supports repair by a single-strand annealing-like mechanism2009In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 106, no 29, 12037-12042 p.Article in journal (Refereed)
    Abstract [en]

    Double-strand breaks (DSBs) represent the most severe DNA lesion a cell can suffer, as they pose the risk of inducing loss of genomic integrity and promote oncogenesis in mammals. Two pathways repair DSBs, nonhomologous end joining (NHEJ) and homologous recombination (HR). With respect to mechanism and genetic requirements, characterization of these pathways has revealed a large degree of functional separation between the two. Nej1 is a cell-type specific regulator essential to NHEJ in Saccharomyces cerevisiae. Srs2 is a DNA helicase with multiple roles in HR. In this study, we show that Nej1 physically interacts with Srs2. Furthermore, mutational analysis of Nej1 suggests that the interaction was strengthened by Dun1-dependent phosphorylation of Nej1 serines 297/298. Srs2 was previously shown to be recruited to replication forks, where it promotes translesion DNA synthesis. We demonstrate that Srs2 was also efficiently recruited to DSBs generated by the HO endonuclease. Additionally, efficient Srs2 recruitment to this DSB was dependent on Nej1, but independent of mechanisms facilitating Srs2 recruitment to replication forks. Functionally, both Nej1 and Srs2 were required for efficient repair of DSBs with 15-bp overhangs, a repair event reminiscent of a specific type of HR called single-strand annealing (SSA). Moreover, absence of Rad51 suppressed the SSA-defect in srs2 and nej1 strains. We suggest a model in which Nej1 recruits Srs2 to DSBs to promote NHEJ/SSA-like repair by dismantling inappropriately formed Rad51 nucleoprotein filaments. This unexpected link between NHEJ and HR components may represent cross-talk between DSB repair pathways to ensure efficient repair.

  • 22. Casini, Michele
    et al.
    Blenckner, Thorsten
    Stockholm University, Stockholm Resilience Centre, Baltic Nest Institute.
    Moellmann, Christian
    Gardmark, Anna
    Lindegren, Martin
    Llope, Marcos
    Kornilovs, Georgs
    Plikshs, Maris
    Stenseth, Nils Christian
    Predator transitory spillover induces trophic cascades in ecological sinks2012In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 109, no 21, 8185-8189 p.Article in journal (Refereed)
    Abstract [en]

    Understanding the effects of cross-system fluxes is fundamental in ecosystem ecology and biological conservation. Source-sink dynamics and spillover processes may link adjacent ecosystems by movement of organisms across system boundaries. However, effects of temporal variability in these cross-system fluxes on a whole marine ecosystem structure have not yet been presented. Here we show, using 35 y of multitrophic data series from the Baltic Sea, that transitory spillover of the top-predator cod from its main distribution area produces cascading effects in the whole food web of an adjacent and semi-isolated ecosystem. At varying population size, cod expand/contract their distribution range and invade/retreat from the neighboring Gulf of Riga, thereby affecting the local prey population of herring and, indirectly, zooplankton and phytoplankton via top-down control. The Gulf of Riga can be considered for cod a true sink habitat, where in the absence of immigration from the source areas of the central Baltic Sea the cod population goes extinct due to the absence of suitable spawning grounds. Our results add a metaecosystem perspective to the ongoing intense scientific debate on the key role of top predators in structuring natural systems. The integration of regional and local processes is central to predict species and ecosystem responses to future climate changes and ongoing anthropogenic disturbances.

  • 23.
    Chi Fru, Ernest
    et al.
    Stockholm University, Faculty of Science, Department of Geological Sciences.
    Rodriguez, Nathalie P.
    Stockholm University, Faculty of Science, Department of Geological Sciences.
    Partin, Camille A.
    Lalonde, Stefan V.
    Andersson, Per
    Weiss, Dominik J.
    El Albani, Abderrazak
    Rodushkin, Ilia
    Konhauser, Kurt O.
    Cu isotopes in marine black shales record the Great Oxidation Event2016In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 113, no 18, 4941-4946 p.Article in journal (Refereed)
    Abstract [en]

    The oxygenation of the atmosphere similar to 2.45-2.32 billion years ago (Ga) is one of the most significant geological events to have affected Earth's redox history. Our understanding of the timing and processes surrounding this key transition is largely dependent on the development of redox-sensitive proxies, many of which remain unexplored. Here we report a shift from negative to positive copper isotopic compositions (delta Cu-65(ERM-AE633)) in organic carbon-rich shales spanning the period 2.66-2.08 Ga. We suggest that, before 2.3 Ga, a muted oxidative supply of weathering-derived copper enriched in Cu-65, along with the preferential removal of Cu-65 by iron oxides, left seawater and marine biomass depleted in Cu-65 but enriched in Cu-63. As banded iron formation deposition waned and continentally sourced Cu became more important, biomass sampled a dissolved Cu reservoir that was progressively less fractionated relative to the continental pool. This evolution toward heavy delta Cu-65 values coincides with a shift to negative sedimentary delta Fe-56 values and increased marine sulfate after the Great Oxidation Event (GOE), and is traceable through Phanerozoic shales to modern marine settings, where marine dissolved and sedimentary delta Cu-65 values are universally positive. Our finding of an important shift in sedimentary Cu isotope compositions across the GOE provides new insights into the Precambrian marine cycling of this critical micronutrient, and demonstrates the proxy potential for sedimentary Cu isotope compositions in the study of biogeochemical cycles and oceanic redox balance in the past.

  • 24. Chung, J S
    et al.
    Dircksen, Henrich
    Institute of Zoophysiology, University of Bonn, Germany.
    Webster, S G
    A remarkable, precisely timed release of hyperglycemic hormone from endocrine cells in the gut is associated with ecdysis in the crab Carcinus maenas1999In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 96, no 23, 13103-7 p.Article in journal (Refereed)
    Abstract [en]

    Molting or ecdysis is the most fundamentally important process in arthropod life history, because shedding of the exoskeleton is an absolute prerequisite for growth and metamorphosis. Although the hormonal mechanisms driving ecdysis in insects have been studied extensively, nothing is known about these processes in crustaceans. During late premolt and during ecdysis in the crab Carcinus maenas, we observed a precise and reproducible surge in hemolymph hyperglycemic hormone (CHH) levels, which was over 100-fold greater than levels seen in intermolt animals. The source of this hormone surge was not from the eyestalk neurosecretory tissues but from previously undescribed endocrine cells (paraneurons), in defined areas of the foregut and hindgut. During premolt (the only time when CHH is expressed by these tissues), the gut is the largest endocrine tissue in the crab. The CHH surge, which is a result of an unusual, almost complete discharge of the contents of the gut endocrine cell, regulates water and ion uptake during molting, thus allowing the swelling necessary for successful ecdysis and the subsequent increase in size during postmolt. This study defines an endocrine brain/gut axis in the arthropods. We propose that the ionoregulatory process controlled by CHH may be common to arthropods, in that, for insects, a similar mechanism seems to be involved in antidiuresis. It also seems likely that a cascade of very precisely coordinated release of (neuro) hormones controls ecdysis.

  • 25. Cinner, Joshua E.
    et al.
    McClanahan, Tim R.
    MacNeil, M. Aaron
    Graham, Nicholas A. J.
    Daw, Tim M.
    Stockholm University, Stockholm Resilience Centre.
    Mukminin, Ahmad
    Feary, David A.
    Rabearisoa, Ando L.
    Wamukota, Andrew
    Jiddawi, Narriman
    Campbell, Stuart J.
    Baird, Andrew H.
    Januchowski-Hartley, Fraser A.
    Hamed, Salum
    Lahari, Rachael
    Morove, Tau
    Kuange, John
    Comanagement of coral reef social ecological systems2012In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 109, no 14, 5219-5222 p.Article in journal (Refereed)
    Abstract [en]

    In an effort to deliver better outcomes for people and the ecosystems they depend on, many governments and civil society groups are engaging natural resource users in collaborative management arrangements (frequently called comanagement). However, there are few empirical studies demonstrating the social and institutional conditions conducive to successful comanagement outcomes, especially in small-scale fisheries. Here, we evaluate 42 comanagement arrangements across five countries and show that: (i) comanagement is largely successful at meeting social and ecological goals; (ii) comanagement tends to benefit wealthier resource users; (iii) resource overexploitation is most strongly influenced by market access and users' dependence on resources; and (iv) institutional characteristics strongly influence livelihood and compliance outcomes, yet have little effect on ecological conditions.

  • 26. Cintron-Colon, Rigo
    et al.
    Sanchez-Alavez, Manuel
    Nguyen, William
    Mori, Simone
    Gonzalez-Rivera, Ruben
    Lien, Tiffany
    Bartfai, Tamas
    Stockholm University, Faculty of Science, Department of Neurochemistry.
    Aid, Saba
    Francois, Jean-Christophe
    Holzenbergerf, Martin
    Conti, Bruno
    Insulin-like growth factor 1 receptor regulates hypothermia during calorie restriction2017In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 114, no 36, 9731-9736 p.Article in journal (Refereed)
    Abstract [en]

    When food resources are scarce, endothermic animals can lower core body temperature (Tb). This phenomenon is believed to be part of an adaptive mechanism that may have evolved to conserve energy until more food becomes available. Here, we found in the mouse that the insulin-like growth factor 1 receptor (IGF-1R) controls this response in the central nervous system. Pharmacological or genetic inhibition of IGF-1R enhanced the reduction of temperature and of energy expenditure during calorie restriction. Full blockade of IGF-1R affected female and male mice similarly. In contrast, genetic IGF-1R dosage was effective only in females, where it also induced transient and estrusspecific hypothermia in animals fed ad libitum. These effects were regulated in the brain, as only central, not peripheral, pharmacological activation of IGF-1R prevented hypothermia during calorie restriction. Targeted IGF-1R knockout selectively in forebrain neurons revealed that IGF signaling also modulates calorie restriction-dependent Tb regulation in regions rostral of the canonical hypothalamic nuclei involved in controlling body temperature. In aggregate, these data identify central IGF-1R as a mediator of the integration of nutrient and temperature homeostasis. They also show that calorie restriction, IGF-1R signaling, and body temperature, three of the main regulators of metabolism, aging, and longevity, are components of the same pathway.

  • 27.
    Cymer, Florian
    et al.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    von Heijne, Gunnar
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Cotranslational folding of membrane proteins probed by arrest-peptide-mediated force measurements2013In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 110, no 36, 14640-14645 p.Article in journal (Refereed)
    Abstract [en]

    Polytopic membrane proteins are inserted cotranslationally into target membranes by ribosome-translocon complexes. It is, however, unclear when during the insertion process specific interactions between the transmembrane helices start to form. Here, we use a recently developed in vivo technique to measure pulling forces acting on transmembrane helices during their cotranslational insertion into the inner membrane of Escherichia coli to study the earliest steps of tertiary folding of five polytopic membrane proteins. We find that interactions between residues in a C-terminally located transmembrane helix and in more N-terminally located helices can be detected already at the point when the C-terminal helix partitions from the translocon into the membrane. Our findings pinpoint the earliest steps of tertiary structure formation and open up possibilities to study the cotranslational folding of polytopic membrane proteins.

  • 28. Dahl, Tais W.
    et al.
    Hammarlund, Emma U.
    Stockholm University, Faculty of Science, Department of Geological Sciences.
    Anbar, Ariel D.
    Bond, David P. G.
    Gill, Benjamin C.
    Gordon, Gwyneth W.
    Knoll, Andrew H.
    Canfield, Donald E.
    Reply to Butterfield: The Devonian radiation of large predatory fish coincided with elevated athospheric oxygen levels2011In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 108, no 9, E29- p.Article in journal (Refereed)
    Abstract [en]

    We welcome this opportunity to clarify the conclusions and implications of our recent publication in PNAS. Butterfield (1) raises four issues regarding the oxygenation of the Paleozoic Earth's surface and its correlation to animal evolution. Our geochemical and paleontological data supported ocean oxygenation in the Silurian-Early Devonian (2), a critical transition in Earth history that influenced biogeochemical cycles and biological systems.

    First, Butterfield suggests that evidence of charcoal in late Silurian rocks is incompatible with our claim that the earlier Paleozoic atmosphere had oxygen levels below 50% PAL (present-day atmospheric level). This counterargument rests on the assumption that the “fire window” of 62–166% PAL oxygen is well defined, but this is not the case (3).

  • 29. Dahl, Tais W.
    et al.
    Hammarlund, Emma U.
    Stockholm University, Faculty of Science, Department of Geological Sciences.
    Anbar, Ariel D.
    Bond, David P. G.
    Gill, Benjamin C.
    Gordon, Gwyneth W.
    Knoll, Andrew H.
    Nielsen, Arne T.
    Schovsbo, Niels H.
    Canfield, Donald E.
    Devonian rise in atmospheric oxygen correlated to the radiations of terrestrial plants and large predatory fish2010In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 107, no 42, 17911-17915 p.Article in journal (Refereed)
    Abstract [en]

    The evolution of Earth's biota is intimately linked to the oxygenation of the oceans and atmosphere. We use the isotopic composition and concentration of molybdenum (Mo) in sedimentary rocks to explore this relationship. Our results indicate two episodes of global ocean oxygenation. The first coincides with the emergence of the Ediacaran fauna, including large, motile bilaterian animals, ca. 550-560 million year ago (Ma), reinforcing previous geochemical indications that Earth surface oxygenation facilitated this radiation. The second, perhaps larger, oxygenation took place around 400 Ma, well after the initial rise of animals and, therefore, suggesting that early metazoans evolved in a relatively low oxygen environment. This later oxygenation correlates with the diversification of vascular plants, which likely contributed to increased oxygenation through the enhanced burial of organic carbon in sediments. It also correlates with a pronounced radiation of large predatory fish, animals with high oxygen demand. We thereby couple the redox history of the atmosphere and oceans to major events in animal evolution.

  • 30.
    Dalén, Love
    et al.
    Stockholm University, Faculty of Science, Department of Zoology.
    Nyström, Veronica
    Stockholm University, Faculty of Science, Department of Zoology.
    Valdiosera, Cristina
    Germonpre, Mietje
    Sablin, Mikhail
    Turner, Elaine
    Angerbjörn, Anders
    Stockholm University, Faculty of Science, Department of Zoology.
    Arsuaga, Juan Luis
    Götherström, Anders
    Ancient DNA reveals lack of postglacial habitat tracking in the arctic fox2007In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 104, no 16, 6726-6729 p.Article in journal (Refereed)
    Abstract [en]

    How species respond to an increased availability of habitat, for example at the end of the last glaciation, has been well established. In contrast, little is known about the opposite process, when the amount of habitat decreases. The hypothesis of habitat tracking predicts that species should be able to track both increases and decreases in habitat availability. The alternative hypothesis is that populations outside refugia become extinct during periods of unsuitable climate. To test these hypotheses, we used ancient DNA techniques to examine genetic variation in the arctic fox (Alopex lagopus) through an expansion/contraction cycle. The results show that the arctic fox in midlatitude Europe became extinct at the end of the Pleistocene and did not track the habitat when it shifted to the north. Instead, a high genetic similarity between the extant populations in Scandinavia and Siberia suggests an eastern origin for the Scandinavian population at the end of the last glaciation. These results provide new insights into how species respond to climate change, since they suggest that populations are unable to track decreases in habitat avaliability. This implies that arctic species may be particularly vulnerable to increases in global temperatures.

  • 31. d'Amour, Christopher Bren
    et al.
    Reitsma, Femke
    Baiocchi, Giovanni
    Barthel, Stephan
    Stockholm University, Faculty of Science, Stockholm Resilience Centre. University of Gävle, Sweden.
    Guneralp, Burak
    Erb, Karl-Heinz
    Haberl, Helmut
    Creutzig, Felix
    Seto, Karen C.
    Future urban land expansion and implications for global croplands2017In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 114, no 34, 8939-8944 p.Article in journal (Refereed)
    Abstract [en]

    Urban expansion often occurs on croplands. However, there is little scientific understanding of how global patterns of future urban expansion will affect the world's cultivated areas. Here, we combine spatially explicit projections of urban expansion with datasets on global croplands and crop yields. Our results show that urban expansion will result in a 1.8-2.4% loss of global croplands by 2030, with substantial regional disparities. About 80% of global cropland loss from urban expansion will take place in Asia and Africa. In both Asia and Africa, much of the cropland that will be lost is more than twice as productive as national averages. Asia will experience the highest absolute loss in cropland, whereas African countries will experience the highest percentage loss of cropland. Globally, the croplands that are likely to be lost were responsible for 3-4% of worldwide crop production in 2000. Urban expansion is expected to take place on cropland that is 1.77 times more productive than the global average. The loss of cropland is likely to be accompanied by other sustainability risks and threatens livelihoods, with diverging characteristics for different megaurban regions. Governance of urban area expansion thus emerges as a key area for securing livelihoods in the agrarian economies of the Global South.

  • 32. Daniel, Terry C.
    et al.
    Muhar, Andreas
    Arnberger, Arne
    Aznar, Olivier
    Boyd, James W.
    Chan, Kai M. A.
    Costanza, Robert
    Elmqvist, Thomas
    Stockholm University, Stockholm Resilience Centre.
    Flint, Courtney G.
    Gobster, Paul H.
    Gret-Regamey, Adrienne
    Lave, Rebecca
    Muhar, Susanne
    Penker, Marianne
    Ribe, Robert G.
    Schauppenlehner, Thomas
    Sikor, Thomas
    Soloviy, Ihor
    Spierenburg, Marja
    Taczanowska, Karolina
    Tam, Jordan
    von der Dunk, Andreas
    Contributions of cultural services to the ecosystem services agenda2012In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 109, no 23, 8812-8819 p.Article in journal (Refereed)
    Abstract [en]

    Cultural ecosystem services (ES) are consistently recognized but not yet adequately defined or integrated within the ES framework. A substantial body of models, methods, and data relevant to cultural services has been developed within the social and behavioral sciences before and outside of the ES approach. A selective review of work in landscape aesthetics, cultural heritage, outdoor recreation, and spiritual significance demonstrates opportunities for operationally defining cultural services in terms of socioecological models, consistent with the larger set of ES. Such models explicitly link ecological structures and functions with cultural values and benefits, facilitating communication between scientists and stakeholders and enabling economic, multicriterion, deliberative evaluation and other methods that can clarify tradeoffs and synergies involving cultural ES. Based on this approach, a common representation is offered that frames cultural services, along with all ES, by the relative contribution of relevant ecological structures and functions and by applicable social evaluation approaches. This perspective provides a foundation for merging ecological and social science epistemologies to define and integrate cultural services better within the broader ES framework.

  • 33. Danielsson, Frida
    et al.
    Skogs, Marie
    Huss, Mikael
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Rexhepaj, Elton
    O'Hurley, Gillian
    Klevebring, Daniel
    Ponten, Fredrik
    Gad, Annica K. B.
    Uhlen, Mathias
    Lundberg, Emma
    Majority of differentially expressed genes are down-regulated during malignant transformation in a four-stage model2013In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 110, no 17, 6853-6858 p.Article in journal (Refereed)
    Abstract [en]

    The transformation of normal cells to malignant, metastatic tumor cells is a multistep process caused by the sequential acquirement of genetic changes. To identify these changes, we compared the transcriptomes and levels and distribution of proteins in a four-stage cell model of isogenically matched normal, immortalized, transformed, and metastatic human cells, using deep transcriptome sequencing and immunofluorescence microscopy. The data show that similar to 6% (n = 1,357) of the human protein-coding genes are differentially expressed across the stages in the model. Interestingly, the majority of these genes are down-regulated, linking malignant transformation to dedifferentiation. The up-regulated genes are mainly components that control cellular proliferation, whereas the down-regulated genes consist of proteins exposed on or secreted from the cell surface. As many of the identified gene products control basic cellular functions that are defective in cancers, the data provide candidates for follow-up studies to investigate their functional roles in tumor formation. When we further compared the expression levels of four of the identified proteins in clinical cancer cohorts, similar differences were observed between benign and cancer cells, as in the cell model. This shows that this comprehensive demonstration of the molecular changes underlying malignant transformation is a relevant model to study the process of tumor formation.

  • 34.
    Danielsson, Jens
    et al.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Awad, Wael
    Saraboji, Kadhirvel
    Kurnik, Martin
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Lang, Lisa
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Leinartaité, Lina
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Marklund, Stefan L.
    Logan, Derek T.
    Oliveberg, Mikael
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    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, 3829-3834 p.Article 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?

  • 35.
    Danielsson, Jens
    et al.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Mu, Xin
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Lang, Lisa
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Wang, Huabing
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Binolfi, Andres
    Theillet, Franois-Xavier
    Bekei, Beata
    Logan, Derek T.
    Selenko, Philipp
    Wennerström, Håkan
    Oliveberg, Mikael
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Thermodynamics of protein destabilization in live cells2015In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 112, no 40, 12402-12407 p.Article in journal (Refereed)
    Abstract [en]

    Although protein folding and stability have been well explored under simplified conditions in vitro, it is yet unclear how these basic self-organization events are modulated by the crowded interior of live cells. To find out, we use here in-cell NMR to follow at atomic resolution the thermal unfolding of a beta-barrel protein inside mammalian and bacterial cells. Challenging the view from in vitro crowding effects, we find that the cells destabilize the protein at 37 degrees C but with a conspicuous twist: While the melting temperature goes down the cold unfolding moves into the physiological regime, coupled to an augmented heat-capacity change. The effect seems induced by transient, sequence-specific, interactions with the cellular components, acting preferentially on the unfolded ensemble. This points to a model where the in vivo influence on protein behavior is case specific, determined by the individual protein's interplay with the functionally optimized interaction landscape of the cellular interior.

  • 36.
    Daw, Tim M.
    et al.
    Stockholm University, Faculty of Science, Stockholm Resilience Centre. University of East Anglia, United Kingdom.
    Coulthard, Sarah
    Cheung, William W. L.
    Brown, Katrina
    Abunge, Caroline
    Galafassi, Diego
    Stockholm University, Faculty of Science, Stockholm Resilience Centre.
    Peterson, Garry D.
    Stockholm University, Faculty of Science, Stockholm Resilience Centre.
    McClanahan, Tim R.
    Omukoto, Johnstone O.
    Munyi, Lydiah
    Evaluating taboo trade-offs in ecosystems services and human well-being2015In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 112, no 22, 6949-6954 p.Article in journal (Refereed)
    Abstract [en]

    Managing ecosystems for multiple ecosystem services and balancing the well-being of diverse stakeholders involves different kinds of trade-offs. Often trade-offs involve noneconomic and difficult-to-evaluate values, such as cultural identity, employment, the well-being of poor people, or particular species or ecosystem structures. Although trade-offs need to be considered for successful environmental management, they are often overlooked in favor of win-wins. Management and policy decisions demand approaches that can explicitly acknowledge and evaluate diverse trade-offs. We identified a diversity of apparent trade-offs in a small-scale tropical fishery when ecological simulations were integrated with participatory assessments of social-ecological system structure and stakeholders' well-being. Despite an apparent win-win between conservation and profitability at the aggregate scale, food production, employment, and well-being of marginalized stakeholders were differentially influenced by management decisions leading to trade-offs. Some of these trade-offs were suggested to be taboo trade-offs between morally incommensurable values, such as between profits and the well-being of marginalized women. These were not previously recognized as management issues. Stakeholders explored and deliberated over trade-offs supported by an interactive toy model representing key system trade-offs, alongside qualitative narrative scenarios of the future. The concept of taboo trade-offs suggests that psychological bias and social sensitivity may exclude key issues from decision making, which can result in policies that are difficult to implement. Our participatory modeling and scenarios approach has the potential to increase awareness of such trade-offs, promote discussion of what is acceptable, and potentially identify and reduce obstacles to management compliance.

  • 37. De Frenne, Pieter
    et al.
    Rodriguez-Sanchez, Francisco
    Coomes, David Anthony
    Baeten, Lander
    Verstraeten, Gorik
    Vellend, Mark
    Bernhardt-Roemermann, Markus
    Brown, Carissa D.
    Brunet, Jorg
    Cornelis, Johnny
    Decocq, Guillaume M.
    Dierschke, Hartmut
    Eriksson, Ove
    Stockholm University, Faculty of Science, Department of Ecology, Environment and Plant Sciences.
    Gilliam, Frank S.
    Hedl, Radim
    Heinken, Thilo
    Hermy, Martin
    Hommel, Patrick
    Jenkins, Michael A.
    Kelly, Daniel L.
    Kirby, Keith J.
    Mitchell, Fraser J. G.
    Naaf, Tobias
    Newman, Miles
    Peterken, George
    Petrik, Petr
    Schultz, Jan
    Sonnier, Gregory
    Van Calster, Hans
    Waller, Donald M.
    Walther, Gian-Reto
    White, Peter S.
    Woods, Kerry D.
    Wulf, Monika
    Graae, Bente Jessen
    Verheyen, Kris
    Microclimate moderates plant responses to macroclimate warming2013In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 110, no 46, 18561-18565 p.Article in journal (Refereed)
    Abstract [en]

    Recent global warming is acting across marine, freshwater, and terrestrial ecosystems to favor species adapted to warmer conditions and/or reduce the abundance of cold-adapted organisms (i.e., thermophilization of communities). Lack of community responses to increased temperature, however, has also been reported for several taxa and regions, suggesting that climatic lags may be frequent. Here we show that microclimatic effects brought about by forest canopy closure can buffer biotic responses to macroclimate warming, thus explaining an apparent climatic lag. Using data from 1,409 vegetation plots in European and North American temperate forests, each surveyed at least twice over an interval of 12-67 y, we document significant thermophilization of ground-layer plant communities. These changes reflect concurrent declines in species adapted to cooler conditions and increases in species adapted to warmer conditions. However, thermophilization, particularly the increase of warm-adapted species, is attenuated in forests whose canopies have become denser, probably reflecting cooler growing-season ground temperatures via increased shading. As standing stocks of trees have increased in many temperate forests in recent decades, local microclimatic effects may commonly be moderating the impacts of macroclimate warming on forest understories. Conversely, increases in harvesting woody biomass-e.g., for bioenergy-may open forest canopies and accelerate thermophilization of temperate forest biodiversity.

  • 38. Douglas, Gavin M.
    et al.
    Gos, Gesseca
    Steige, Kim A.
    Salcedo, Adriana
    Holm, Karl
    Josephs, Emily B.
    Arunkumar, Ramesh
    Agren, J. Arvid
    Hazzouri, Khaled M.
    Wang, Wei
    Platts, Adrian E.
    Williamson, Robert J.
    Neuffer, Barbara
    Lascoux, Martin
    Slotte, Tanja
    Stockholm University, Faculty of Science, Department of Ecology, Environment and Plant Sciences. Uppsala University, Sweden.
    Wright, Stephen I.
    Hybrid origins and the earliest stages of diploidization in the highly successful recent polyploid Capsella bursa-pastoris2015In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 112, no 9, 2806-2811 p.Article in journal (Refereed)
    Abstract [en]

    Whole-genome duplication (WGD) events have occurred repeatedly during flowering plant evolution, and there is growing evidence for predictable patterns of gene retention and loss following polyploidization. Despite these important insights, the rate and processes governing the earliest stages of diploidization remain poorly understood, and the relative importance of genetic drift, positive selection, and relaxed purifying selection in the process of gene degeneration and loss is unclear. Here, we conduct whole-genome resequencing in Capsella bursa-pastoris, a recently formed tetraploid with one of the most widespread species distributions of any angiosperm. Whole-genome data provide strong support for recent hybrid origins of the tetraploid species within the past 100,000-300,000 y from two diploid progenitors in the Capsella genus. Major-effect inactivating mutations are frequent, but many were inherited from the parental species and show no evidence of being fixed by positive selection. Despite a lack of large-scale gene loss, we observe a decrease in the efficacy of natural selection genome-wide due to the combined effects of demography, selfing, and genome redundancy from WGD. Our results suggest that the earliest stages of diploidization are associated with quantitative genome-wide decreases in the strength and efficacy of selection rather than rapid gene loss, and that non-functionalization can receive a head start through a legacy of deleterious variants and differential expression originating in parental diploid populations.

  • 39. Edger, Patrick P.
    et al.
    Heidel-Fischer, Hanna M.
    Bekaert, Michael
    Rota, Jadranka
    Gloeckner, Gernot
    Platts, Adrian E.
    Heckel, David G.
    Der, Joshua P.
    Wafula, Eric K.
    Tang, Michelle
    Hofberger, Johannes A.
    Smithson, Ann
    Hall, Jocelyn C.
    Blanchette, Matthieu
    Bureau, Thomas E.
    Wright, Stephen I.
    dePamphilis, Claude W.
    Schranz, M. Eric
    Barker, Michael S.
    Conant, Gavin C.
    Wahlberg, Niklas
    Vogel, Heiko
    Pires, J. Chris
    Wheat, Christopher W.
    Stockholm University, Faculty of Science, Department of Zoology.
    The butterfly plant arms-race escalated by gene and genome duplications2015In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 112, no 27, 8362-8366 p.Article in journal (Refereed)
    Abstract [en]

    Coevolutionary interactions are thought to have spurred the evolution of key innovations and driven the diversification of much of life on Earth. However, the genetic and evolutionary basis of the innovations that facilitate such interactions remains poorly understood. We examined the coevolutionary interactions between plants (Brassicales) and butterflies (Pieridae), and uncovered evidence for an escalating evolutionary arms-race. Although gradual changes in trait complexity appear to have been facilitated by allelic turnover, key innovations are associated with gene and genome duplications. Furthermore, we show that the origins of both chemical defenses and of molecular counter adaptations were associated with shifts in diversification rates during the arms-race. These findings provide an important connection between the origins of biodiversity, coevolution, and the role of gene and genome duplications as a substrate for novel traits.

  • 40.
    Edin, Michaela
    et al.
    Stockholm University, Faculty of Science, Department of Organic Chemistry.
    Steinreiber, Johannes
    Bäckvall, Jan-E.
    One-pot synthesis of enantiopure syn-1,3-diacetates from racemic diastereomeric mixtures of 1,3-diols by dynamic kinetic asymmetric transformation2004In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 101, 5761-5766 p.Article in journal (Refereed)
  • 41.
    Englund, Markus
    Stockholm University, Faculty of Science, Department of Botany.
    Clade size is not always an appropriate measure of diversification2011In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 108, no 17, E84-E84 p.Article in journal (Refereed)
  • 42. Ericsson, Malin
    et al.
    Lundholm, Cecilia
    Fors, Stefan
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Dahl Aslan, Anna K.
    Zavala, Catalina
    Reynolds, Chandra A.
    Pedersen, Nancy L.
    Childhood social class and cognitive aging in the Swedish Adoption/Twin Study of Aging2017In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 114, no 27, 7001-7006 p.Article in journal (Refereed)
    Abstract [en]

    In this report we analyzed genetically informative data to investigate within-person change and between-person differences in late-life cognitive abilities as a function of childhood social class. We used data from nine testing occasions spanning 28 y in the Swedish Adoption/Twin Study of Aging and parental social class based on the Swedish socioeconomic index. Cognitive ability included a general factor and the four domains of verbal, fluid, memory, and perceptual speed. Latent growth curve models of the longitudinal data tested whether level and change in cognitive performance differed as a function of childhood social class. Between-within twin-pair analyses were performed on twins reared apart to assess familial confounding. Childhood social class was significantly associated with mean-level cognitive performance at age 65 y, but not with rate of cognitive change. The association decreased in magnitude but remained significant after adjustments for level of education and the degree to which the rearing family was supportive toward education. A between-pair effect of childhood social class was significant in all cognitive domains, whereas within-pair estimates were attenuated, indicating genetic confounding. Thus, childhood social class is important for cognitive performance in adulthood on a population level, but the association is largely attributable to genetic influences.

  • 43. Feng, Xiaojuan
    et al.
    Vonk, Jorien E.
    van Dongen, Bart E.
    Gustafsson, Örjan
    Stockholm University, Faculty of Science, Department of Applied Environmental Science (ITM).
    Semiletov, Igor P.
    Dudarev, Oleg V.
    Wang, Zhiheng
    Montlucon, Daniel B.
    Wacker, Lukas
    Eglinton, Timothy I.
    Differential mobilization of terrestrial carbon pools in Eurasian Arctic river basins2013In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 110, no 35, 14168-14173 p.Article in journal (Refereed)
    Abstract [en]

    Mobilization of Arctic permafrost carbon is expected to increase with warming-induced thawing. However, this effect is challenging to assess due to the diverse processes controlling the release of various organic carbon (OC) pools from heterogeneous Arctic landscapes. Here, by radiocarbon dating various terrestrial OC components in fluvially and coastally integrated estuarine sediments, we present a unique framework for deconvoluting the contrasting mobilization mechanisms of surface vs. deep (permafrost) carbon pools across the climosequence of the Eurasian Arctic. Vascular plant-derived lignin phenol C-14 contents reveal significant inputs of young carbon from surface sources whose delivery is dominantly controlled by river runoff. In contrast, plant wax lipids predominantly trace ancient (permafrost) OC that is preferentially mobilized from discontinuous permafrost regions, where hydrological conduits penetrate deeper into soils and thermokarst erosion occurs more frequently. Because river runoff has significantly increased across the Eurasian Arctic in recent decades, we estimate from an isotopic mixing model that, in tandem with an increased transfer of young surface carbon, the proportion of mobilized terrestrial OC accounted for by ancient carbon has increased by 3-6% between 1985 and 2004. These findings suggest that although partly masked by surface carbon export, climate change-induced mobilization of old permafrost carbon is well underway in the Arctic.

  • 44. Ferwerda, Bart
    et al.
    Alonso, Santos
    Banahan, Kathy
    McCall, Matthew B B
    Giamarellos-Bourboulis, Evangelos J
    Ramakers, Bart P
    Mouktaroudi, Maria
    Fain, Pamela R
    Izagirre, Neskuts
    Syafruddin, Din
    Cristea, Tudor
    Mockenhaupt, Frank P
    Troye-Blomberg, Marita
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Kumpf, Oliver
    Maiga, Boubacar
    Dolo, Amagana
    Doumbo, Ogobara
    Sundaresan, Santhosh
    Bedu-Addo, George
    van Crevel, Reinout
    Hamann, Lutz
    Oh, Djin-Ye
    Schumann, Ralf R
    Joosten, Leo A B
    de la Rúa, Concepcion
    Sauerwein, Robert
    Drenth, Joost P H
    Kullberg, Bart-Jan
    van der Ven, André J A M
    Hill, Adrian V
    Pickkers, Peter
    van der Meer, Jos W M
    O'Neill, Luke A J
    Netea, Mihai G
    Functional and genetic evidence that the Mal/TIRAP allele variant 180L has been selected by providing protection against septic shock.2009In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 106, no 25, 10272-10277 p.Article in journal (Refereed)
    Abstract [en]

    Adequate responses by our innate immune system toward invading pathogens were of vital importance for surviving infections, especially before the antibiotic era. Recently, a polymorphism in Mal (Ser180Leu, TIRAP rs8177374), an important adaptor protein downstream of the Toll-like receptor (TLR) 2 and 4 pathways, has been described to provide protection against a broad range of infectious pathogens. We assessed the functional effects of this polymorphism in human experimental endotoxemia, and we demonstrate that individuals bearing the TIRAP 180L allele display an increased, innate immune response to TLR4 and TLR2 ligands, but not to TLR9 stimulation. This phenotype has been related to an increased resistance to infection. However, an overshoot in the release of proinflammatory cytokines by TIRAP 180L homozygous individuals suggests a scenario of balanced evolution. We have also investigated the worldwide distribution of the Ser180Leu polymorphism in 14 populations around the globe to correlate the genetic makeup of TIRAP with the local infectious pressures. Based on the immunological, clinical, and genetic data, we propose that this mutation might have been selected in West Eurasia during the early settlement of this region after the out-of-Africa migration of modern Homo sapiens. This combination of functional and genetic data provides unique insights to our understanding of the pathogenesis of sepsis.

  • 45.
    Fetzer, Ingo
    et al.
    Stockholm University, Faculty of Science, Stockholm Resilience Centre. Helmholtz Centre for Environmental Research–UFZ, Germany.
    Johst, Karin
    Schaewe, Robert
    Banitz, Thomas
    Harms, Hauke
    Chatzinotas, Antonis
    The extent of functional redundancy changes as species' roles shift in different environments2015In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 112, no 48, 14888-14893 p.Article in journal (Refereed)
    Abstract [en]

    Assessing the ecological impacts of environmental change requires knowledge of the relationship between biodiversity and ecosystem functioning. The exact nature of this relationship can differ considerably between ecosystems, with consequences for the efficacy of species diversity as a buffer against environmental change. Using a microbial model system, we show that the relationship can vary depending on environmental conditions. Shapes suggesting functional redundancy in one environment can change, suggesting functional differences in another environment. We find that this change is due to shifting species roles and interactions. Species that are functionally redundant in one environment may become pivotal in another. Thus, caution is advised in drawing conclusions about functional redundancy based on a single environmental situation. It also implies that species richness is important because it provides a pool of species with potentially relevant traits. These species may turn out to be essential performers or partners in new interspecific interactions after environmental change. Therefore, our results challenge the generality of functional redundancy.

  • 46. Fitzpatrick, John L.
    et al.
    Montgomerie, Robert
    Desjardins, Julie K.
    Stiver, Kelly A.
    Kolm, Niclas
    Uppsala universitet, Institutionen för ekologi och evolution.
    Balshine, Sigal
    Female promiscuity promotes the evolution of faster sperm in cichlid fishes2009In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 106, no 4, 1128-1132 p.Article in journal (Refereed)
    Abstract [en]

    Sperm competition, the contest among ejaculates from rival males to fertilize ova of a female, is a common and powerful evolutionary force influencing ejaculate traits. During competitive interactions between ejaculates, longer and faster spermatozoa are expected to have an edge; however, to date, there has been mixed support for this key prediction from sperm competition theory. Here, we use the spectacular radiation of cichlid fishes from Lake Tanganyika to examine sperm characteristics in 29 closely related species. We provide phylogenetically robust evidence that species experiencing greater levels of sperm competition have faster-swimming sperm. We also show that sperm competition selects for increases in the number, size, and longevity of spermatozoa in the ejaculate of a male, and, contrary to expectations from theory, we find no evidence of trade-offs among sperm traits in an interspecific analysis. Also, sperm swimming speed is positively correlated with sperm length among, but not within, species. These different responses to sperm competition at intra-and interspecific levels provide a simple, powerful explanation for equivocal results from previous studies. Using phylogenetic analyses, we also reconstructed the probable evolutionary route of trait evolution in this taxon, and show that, in response to increases in the magnitude of sperm competition, the evolution of sperm traits in this clade began with the evolution of faster (thus, more competitive) sperm.

  • 47.
    Fluman, Nir
    et al.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Tobiasson, Victor
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    von Heijne, Gunnar
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Stable membrane orientations of small dual-topology membrane proteins2017In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 114, no 30, 7987-7992 p.Article in journal (Refereed)
    Abstract [en]

    The topologies of alpha-helical membrane proteins are generally thought to be determined during their cotranslational insertion into the membrane. It is typically assumed that membrane topologies remain static after this process has ended. Recent findings, however, question this static view by suggesting that some parts of, or even the whole protein, can reorient in the membrane on a biologically relevant time scale. Here, we focus on antiparallel homo- or heterodimeric small multidrug resistance proteins and examine whether the individual monomers can undergo reversible topological inversion (flip flop) in the membrane until they are trapped in a fixed orientation by dimerization. By perturbing dimerization using various means, we show that the membrane orientation of a monomer is unaffected by the presence or absence of its dimerization partner. Thus, membrane-inserted monomers attain their final orientations independently of dimerization, suggesting that wholesale topological inversion is an unlikely event in vivo.

  • 48.
    Fröberg, Ralf
    et al.
    Stockholm University, Faculty of Science, Department of Mathematics.
    Ottaviani, Giorgio
    Shapiro, Boris
    Stockholm University, Faculty of Science, Department of Mathematics.
    On the Waring problem for polynomial rings2012In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 109, no 15, 5600-5602 p.Article in journal (Refereed)
    Abstract [en]

    In this note we discuss an analog of the classical Waring problem for C[x(0),x(1),..., x(n)]- Namely, we show that a general homogeneous polynomial p is an element of C[x(0),x(1),..,x(n)] of degree divisible by k >= 2 can be represented as a sum of at most k(n) k-th powers of homogeneous polynomials in C[x(0),x(1),...,x(n)]. Noticeably, k(n) coincides with the number obtained by naive dimension count.

  • 49. Gaines, Robert R.
    et al.
    Hammarlund, Emma U.
    Stockholm University, Faculty of Science, Department of Geological Sciences.
    Hou, Xianguang
    Qie, Chi
    Gabbott, Sarah E.
    Zhao, Yuanlong
    Peng, Jin
    Canfield, Donald E.
    Mechanism for Burgess Shale-type preservation2012In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 109, no 14, 5180-5184 p.Article in journal (Refereed)
    Abstract [en]

    Exceptionally preserved fossil biotas of the Burgess Shale and a handful of other similar Cambrian deposits provide rare but critical insights into the early diversification of animals. The extraordinary preservation of labile tissues in these geographically widespread but temporally restricted soft-bodied fossil assemblages has remained enigmatic since Walcott’s initial discovery in 1909. Here, we demonstrate the mechanism of Burgess Shale-type preservation using sedimentologic and geochemical data from the Chengjiang, Burgess Shale, and five other principal Burgess Shale-type deposits. Sulfur isotope evidence from sedimentary pyrites reveals that the exquisite fossilization of organic remains as carbonaceous compressions resulted from early inhibition of microbial activity in the sediments by means of oxidant deprivation. Low sulfate concentrations in the global ocean and low-oxygen bottom water conditions at the sites of deposition resulted in reduced oxidant availability. Subsequently, rapid entombment of fossils in fine-grained sediments and early sealing of sediments by pervasive carbonate cements at bed tops restricted oxidant flux into the sediments. A permeability barrier, provided by bed-capping cements that were emplaced at the seafloor, is a feature that is shared among Burgess Shale-type deposits, and resulted from the unusually high alkalinity of Cambrian oceans. Thus, Burgess Shale-type preservation of soft-bodied fossil assemblages worldwide was promoted by unique aspects of early Paleozoic seawater chemistry that strongly impacted sediment diagenesis, providing a fundamentally unique record of the immediate aftermath of the “Cambrian explosion.”

  • 50. Gelcich, Stefan
    et al.
    Hughes, Terry P.
    Olsson, Per
    Stockholm University, Stockholm Resilience Centre.
    Folke, Carl
    Stockholm University, Stockholm Resilience Centre.
    Defeo, Omar
    Fernandez, Miriam
    Foale, Simon
    Gunderson, Lance H.
    Rodriguez-Sickert, Carlos
    Scheffer, Marten
    Steneck, Robert S.
    Castilla, Juan C.
    Navigating transformations in governance of Chilean marine coastal resources2010In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 107, no 39, 16794-16799 p.Article in journal (Refereed)
    Abstract [en]

    Marine ecosystems are in decline. New transformational changes in governance are urgently required to cope with overfishing, pollution, global changes, and other drivers of degradation. Here we explore social, political, and ecological aspects of a transformation in governance of Chile's coastal marine resources, from 1980 to today. Critical elements in the initial preparatory phase of the transformation were (i) recognition of the depletion of resource stocks, (ii) scientific knowledge on the ecology and resilience of targeted species and their role in ecosystem dynamics, and (iii) demonstration-scale experimental trials, building on smaller-scale scientific experiments, which identified new management pathways. The trials improved cooperation among scientists and fishers, integrating knowledge and establishing trust. Political turbulence and resource stock collapse provided a window of opportunity that triggered the transformation, supported by new enabling legislation. Essential elements to navigate this transformation were the ability to network knowledge from the local level to influence the decision-making processes at the national level, and a preexisting social network of fishers that provided political leverage through a national confederation of artisanal fishing collectives. The resultant governance scheme includes a revolutionary national system of marine tenure that allocates user rights and responsibilities to fisher collectives. Although fine tuning is necessary to build resilience of this new regime, this transformation has improved the sustainability of the interconnected social-ecological system. Our analysis of how this transformation unfolded provides insights into how the Chilean system could be further developed and identifies generalized pathways for improved governance of marine resources around the world.

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