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  • 1.
    Acuna, Lillian G.
    et al.
    Fundación Ciencia & Vida, Chile ; Universidad Andres Bello, Chile.
    Pablo Cardenas, Juan
    Fundación Ciencia & Vida, Chile ; Universidad Andres Bello, Chile.
    Covarrubias, Paulo C.
    Fundación Ciencia & Vida, Chile ; Universidad Andres Bello, Chile.
    Jose Haristoy, Juan
    Fundación Ciencia & Vida, Chile.
    Flores, Rodrigo
    Fundación Ciencia & Vida, Chile.
    Nuñez, Harold
    Fundación Ciencia & Vida, Chile.
    Riadi, Gonzalo
    Universidad de Talca, Chile.
    Shmaryahu, Amir
    Fundación Ciencia & Vida, Chile.
    Valdes, Jorge
    Center for Systems Biotechnology, Chile.
    Dopson, Mark
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science.
    Rawlings, Douglas E.
    University of Stellenbosch, South Africa.
    Banfield, Jillian F.
    University of California, USA.
    Holmes, David S.
    Fundación Ciencia & Vida, Chile ; Universidad Andres Bello, Chile.
    Quatrini, Raquel
    Fundación Ciencia & Vida, Chile ; Universidad Andres Bello, Chile.
    Architecture and Gene Repertoire of the Flexible Genome of the Extreme Acidophile Acidithiobacillus caldus2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 11, article id e78237Article in journal (Refereed)
    Abstract [en]

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

  • 2.
    Aeinehband, Shahin
    et al.
    Karolinska Institutet.
    Lindblom, Rickard P. F.
    Karolinska Institutet.
    Al Nimer, Faiez
    Karolinska Institutet.
    Vijayaraghavan, Swetha
    Karolinska Institutet.
    Sandholm, Kerstin
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Khademi, Mohsen
    Karolinska Institutet.
    Olsson, Tomas
    Karolinska Institutet.
    Nilsson, Bo
    Uppsala University.
    Nilsson Ekdahl, Kristina
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Uppsala University.
    Darreh-Shori, Taher
    Karolinska Institutet.
    Piehl, Fredrik
    Karolinska Institutet.
    Complement Component C3 and Butyrylcholinesterase Activity Are Associated with Neurodegeneration and Clinical Disability in Multiple Sclerosis2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 4, article id e0122048Article in journal (Refereed)
    Abstract [en]

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

  • 3.
    Al Nima, Ali
    et al.
    Department of Psychology, University of Gothenburg, Gothenburg.
    Rosenberg, Patricia
    Archer, Trevor
    Linnaeus University, Faculty of Social Sciences, Department of Sport Science. Univ Gothenburg, Dept Psychol, S-40020 Gothenburg, Sweden.
    Garcia, Danilo
    Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg.
    Anxiety, Affect, Self-Esteem, and Stress: Mediation and Moderation Effects on Depression2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 9, p. e73265-Article in journal (Refereed)
    Abstract [en]

    Background: Mediation analysis investigates whether a variable (i.e., mediator) changes in regard to an independent variable, in turn, affecting a dependent variable. Moderation analysis, on the other hand, investigates whether the statistical interaction between independent variables predict a dependent variable. Although this difference between these two types of analysis is explicit in current literature, there is still confusion with regard to the mediating and moderating effects of different variables on depression. The purpose of this study was to assess the mediating and moderating effects of anxiety, stress, positive affect, and negative affect on depression. Methods: Two hundred and two university students (males = 93, females = 113) completed questionnaires assessing anxiety, stress, self-esteem, positive and negative affect, and depression. Mediation and moderation analyses were conducted using techniques based on standard multiple regression and hierarchical regression analyses. Main Findings: The results indicated that (i) anxiety partially mediated the effects of both stress and self-esteem upon depression, (ii) that stress partially mediated the effects of anxiety and positive affect upon depression, (iii) that stress completely mediated the effects of self-esteem on depression, and (iv) that there was a significant interaction between stress and negative affect, and between positive affect and negative affect upon depression. Conclusion: The study highlights different research questions that can be investigated depending on whether researchers decide to use the same variables as mediators and/or moderators.

  • 4.
    Atterby, Clara
    et al.
    Uppsala University.
    Börjesson, Stefan
    National Veterinary Institute.
    Ny, Sofia
    Public Health Agency of Sweden;Karolinska Institutet.
    Järhult, Josef D.
    Uppsala University.
    Byfors, Sara
    Public Health Agency of Sweden.
    Bonnedahl, Jonas
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science. Kalmar County Council;Linköping University.
    ESBL-producing Escherichia coli in Swedish gulls: A case of environmental pollution from humans?2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 12, article id e0190380Article in journal (Refereed)
    Abstract [en]

    ESBL-producing bacteria are present in wildlife and the environment might serve as a resistance reservoir. Wild gulls have been described as frequent carriers of ESBL-producing E. coli strains with genotypic characteristics similar to strains found in humans. Therefore, potential dissemination of antibiotic resistance genes and bacteria between the human population and wildlife need to be further investigated. Occurrence and characterization of ESBL-producing E. coli in Swedish wild gulls were assessed and compared to isolates from humans, livestock and surface water collected in the same country and similar time-period. Occurrence of ESBL-producing E. coli in Swedish gulls is about three times higher in gulls compared to Swedish community carriers (17% versus 5%) and the genetic characteristics of the ESBL-producing E. coli population in Swedish wild gulls and Swedish human are similar. ESBL-plasmids IncF-and IncI1-type carrying ESBL-genes blaCTX-M-15 or blaCTX-M-14 were most common in isolates from both gulls and humans, but there was limited evidence of clonal transmission. Isolates from Swedish surface water harbored similar genetic characteristics, which highlights surface waters as potential dissemination routes between wildlife and the human population. Even in a low-prevalence country such as Sweden, the occurrence of ESBL producing E. coli in wild gulls and the human population appears to be connected and the occurrence of ESBL-producing E. coli in Swedish gulls is likely a case of environmental pollution.

  • 5.
    Aurelius, Oskar
    et al.
    Lund University.
    Johansson, Renzo
    Lund University.
    Bågenholm, Viktoria
    Lund University.
    Lundin, Daniel
    Stockholm University.
    Tholander, Fredrik
    Karolinska Institutet.
    Balhuizen, Alexander
    Lund University.
    Beck, Tobias
    University of Göttingen, Germany.
    Sahlin, Margareta
    Stockholm University.
    Sjöberg, Britt-Marie
    Stockholm University.
    Mulliez, Etienne
    Institut de Recherches en Technologies et Sciences pour le Vivant (iRTSV), France.
    Logan, Derek T.
    Lund University.
    The Crystal Structure of Thermotoga maritima Class III Ribonucleotide Reductase Lacks a Radical Cysteine Pre-Positioned in the Active Site2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 7, article id e0128199Article in journal (Refereed)
    Abstract [en]

    Ribonucleotide reductases (RNRs) catalyze the reduction of ribonucleotides to deoxyribonucleotides, the building blocks for DNA synthesis, and are found in all but a few organisms. RNRs use radical chemistry to catalyze the reduction reaction. Despite RNR having evolved several mechanisms for generation of different kinds of essential radicals across a large evolutionary time frame, this initial radical is normally always channelled to a strictly conserved cysteine residue directly adjacent to the substrate for initiation of substrate reduction, and this cysteine has been found in the structures of all RNRs solved to date. We present the crystal structure of an anaerobic RNR from the extreme thermophile Thermotoga maritima (tmNrdD), alone and in several complexes, including with the allosteric effector dATP and its cognate substrate CTP. In the crystal structure of the enzyme as purified, tmNrdD lacks a cysteine for radical transfer to the substrate pre-positioned in the active site. Nevertheless activity assays using anaerobic cell extracts from T. maritima demonstrate that the class III RNR is enzymatically active. Other genetic and microbiological evidence is summarized indicating that the enzyme is important for T. maritima. Mutation of either of two cysteine residues in a disordered loop far from the active site results in inactive enzyme. We discuss the possible mechanisms for radical initiation of substrate reduction given the collected evidence from the crystal structure, our activity assays and other published work. Taken together, the results suggest either that initiation of substrate reduction may involve unprecedented conformational changes in the enzyme to bring one of these cysteine residues to the expected position, or that alternative routes for initiation of the RNR reduction reaction may exist. Finally, we present a phylogenetic analysis showing that the structure of tmNrdD is representative of a new RNR subclass IIIh, present in all Thermotoga species plus a wider group of bacteria from the distantly related phyla Firmicutes, Bacteroidetes and Proteobacteria.

  • 6.
    Baltar, Federico
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science.
    Reinthaler, Thomas
    University of Vienna, Austria.
    Herndl, Gerhard J.
    University of Vienna, Austria;Royal Netherlands Institute for Sea Research (NIOZ), The Netherlands.
    Pinhassi, Jarone
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science.
    Major Effect of Hydrogen Peroxide on Bacterioplankton Metabolism in the Northeast Atlantic2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 4, article id e61051Article in journal (Refereed)
    Abstract [en]

    Reactive oxygen species such as hydrogen peroxide have the potential to alter metabolic rates of marine prokaryotes, ultimately impacting the cycling and bioavailability of nutrients and carbon. We studied the influence of H2O2 on prokaryotic heterotrophic production (PHP) and extracellular enzymatic activities (i.e., beta-glucosidase [BGase], leucine aminopeptidase [LAPase] and alkaline phosphatase [APase]) in the subtropical Atlantic. With increasing concentrations of H2O2 in the range of 100-1000 nM, LAPase, APase and BGase were reduced by up to 11, 23 and 62%, respectively, in the different water layers. Incubation experiments with subsurface waters revealed a strong inhibition of all measured enzymatic activities upon H2O2 amendments in the range of 10-500 nM after 24 h. H2O2 additions also reduced prokaryotic heterotrophic production by 36-100% compared to the rapid increases in production rates occurring in the unamended controls. Our results indicate that oxidative stress caused by H2O2 affects prokaryotic growth and hydrolysis of specific components of the organic matter pool. Thus, we suggest that oxidative stress may have important consequences on marine carbon and energy fluxes.

  • 7.
    Benfatto, Mattias Nilsson
    et al.
    Karolinska Institutet.
    Seimyr, Gustaf Oqvist
    Karolinska Institutet.
    Ygge, Jan
    Karolinska Institutet.
    Pansell, Tony
    Karolinska Institutet.
    Rydberg, Agneta
    Karolinska Institutet.
    Jacobson, Christer
    Linnaeus University, Faculty of Social Sciences, Department of pedagogy.
    Screening for Dyslexia Using Eye Tracking during Reading2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 12, article id e0165508Article in journal (Refereed)
    Abstract [en]

    Dyslexia is a neurodevelopmental reading disability estimated to affect 5-10% of the population. While there is yet no full understanding of the cause of dyslexia, or agreement on its precise definition, it is certain that many individuals suffer persistent problems in learning to read for no apparent reason. Although it is generally agreed that early intervention is the best form of support for children with dyslexia, there is still a lack of efficient and objective means to help identify those at risk during the early years of school. Here we show that it is possible to identify 9-10 year old individuals at risk of persistent reading difficulties by using eye tracking during reading to probe the processes that underlie reading ability. In contrast to current screening methods, which rely on oral or written tests, eye tracking does not depend on the subject to produce some overt verbal response and thus provides a natural means to objectively assess the reading process as it unfolds in real-time. Our study is based on a sample of 97 high-risk subjects with early identified word decoding difficulties and a control group of 88 low-risk subjects. These subjects were selected from a larger population of 2165 school children attending second grade. Using predictive modeling and statistical resampling techniques, we develop classification models from eye tracking records less than one minute in duration and show that the models are able to differentiate high-risk subjects from low-risk subjects with high accuracy. Although dyslexia is fundamentally a language-based learning disability, our results suggest that eye movements in reading can be highly predictive of individual reading ability and that eye tracking can be an efficient means to identify children at risk of long-term reading difficulties.

  • 8.
    Bengtsson, Daniel
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science.
    Avril, Alexis
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science.
    Gunnarsson, Gunnar
    Kristianstad University.
    Elmberg, Johan
    Kristianstad University.
    Söderquist, Pär
    Kristianstad University.
    Norevik, Gabriel
    Ottenby Bird Observatory.
    Tolf, Conny
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science.
    Safi, Kamran
    Max Planck Institute for Ornitholology, Germany ; University of Konstanz, Germany.
    Fiedler, Wolfgang
    Max Planck Institute for Ornitholology, Germany ; University of Konstanz, Germany.
    Wikelski, Martin
    Max Planck Institute for Ornitholology, Germany ; University of Konstanz, Germany.
    Olsen, Björn
    Uppsala University.
    Waldenström, Jonas
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science.
    Movements, Home-Range Size and Habitat Selection of Mallards during Autumn Migration2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 6, article id e100764Article in journal (Refereed)
    Abstract [en]

    The mallard (Anas platyrhynchos) is a focal species in game management, epidemiology and ornithology, but comparably little research has focused on the ecology of the migration seasons. We studied habitat use, time-budgets, home-range sizes, habitat selection, and movements based on spatial data collected with GPS devices attached to wild mallards trapped at an autumn stopover site in the Northwest European flyway. Sixteen individuals (13 males, 3 females) were followed for 15-38 days in October to December 2010. Forty-nine percent (SD = 8.4%) of the ducks' total time, and 85% of the day-time (SD = 28.3%), was spent at sheltered reefs and bays on the coast. Two ducks used ponds, rather than coast, as day-roosts instead. Mallards spent most of the night (76% of total time, SD = 15.8%) on wetlands, mainly on alvar steppe, or in various flooded areas (e.g. coastal meadows). Crop fields with maize were also selectively utilized. Movements between roosting and foraging areas mainly took place at dawn and dusk, and the home-ranges observed in our study are among the largest ever documented for mallards (mean = 6,859 ha; SD = 5,872 ha). This study provides insights into relatively unknown aspects of mallard ecology. The fact that autumn-staging migratory mallards have a well-developed diel activity pattern tightly linked to the use of specific habitats has implications for wetland management, hunting and conservation, as well as for the epidemiology of diseases shared between wildlife and domestic animals.

  • 9.
    Berggren, Hanna
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science.
    Nordahl, Oscar
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science.
    Tibblin, Petter
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science.
    Larsson, Per
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science.
    Forsman, Anders
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science.
    Testing for local adaptation to spawning habitat in sympatric subpopulations of northern pike by reciprocal translocation of embryos2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 5, article id e0154488Article in journal (Refereed)
    Abstract [en]

    We tested for local adaption in early life-history traits by performing a reciprocal translocation experiment with approximately 2500 embryos of pike (Esox lucius) divided in paired split-family batches. The experiment indicated local adaptation in one of the two subpopulations manifested as enhanced hatching success of eggs in the native habitat, both when compared to siblings transferred to a non-native habitat, and when compared to immigrant genotypes from the other subpopulation. Gene-by-environment effects on viability of eggs and larvae were evident in both subpopulations, showing that there existed genetic variation allowing for evolutionary responses to divergent selection, and indicating a capacity for plastic responses to environmental change. Next, we tested for differences in female life-history traits. Results uncovered that females from one population invested more resources into reproduction and also produced more (but smaller) eggs in relation to their body size compared to females from the other population. We suggest that these females have adjusted their reproductive strategies as a counter-adaptation because a high amount of sedimentation on the eggs in that subpopulations spawning habitat might benefit smaller eggs. Collectively, our findings point to adaptive divergence among sympatric subpopulations that are physically separated only for a short period during reproduction and early development – which is rare. These results illustrate how combinations of translocation experiments and field studies of life-history traits might infer about local adaptation and evolutionary divergence among populations. Local adaptations in subdivided populations are important to consider in management and conservation of biodiversity, because they may otherwise be negatively affected by harvesting, supplementation, and reintroduction efforts targeted at endangered populations.

  • 10.
    Bergman, Patrick
    Linnaeus University, Faculty of Social Sciences, Department of Sport Science.
    The number of repeated observations needed to estimate the habitual physical activity of an individual to a given level of precision.2018In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 2, article id e0192117Article in journal (Refereed)
    Abstract [en]

    Physical activity behavior varies naturally from day to day, from week to week and even across seasons. In order to assess the habitual level of physical activity of a person, the person must be monitored for long enough so that the level can be identified, taking into account this natural within-person variation. An important question, and one whose answer has implications for study- and survey design, epidemiological research and population surveillance, is, for how long does an individual need to be monitored before such a habitual level or pattern can be identified to a desired level of precision? The aim of this study was to estimate the number of repeated observations needed to identify the habitual physical activity behaviour of an individual to a given degree of precision. A convenience sample of 50 Swedish adults wore accelerometers during four consecutive weeks. The number of days needed to come within 5-50% of an individual's usual physical activity 95% of the time was calculated. To get an idea of the uncertainty of the estimates all statistical estimates were bootstrapped 2000 times. The mean number of days of measurement needed for the observation to, with 95% confidence, be within 20% of the habitual physical activity of an individual is highest for vigorous physical activity, for which 182 days are needed. For sedentary behaviour the equivalent number of days is 2.4. To capture 80% of the sample to within ±20% of their habitual level of physical activity, 3.4 days is needed if sedentary behavior is the outcome of interest, and 34.8 days for MVPA. The present study shows that for analyses requiring accurate data at the individual level a longer measurement collection period than the traditional 7-day protocol should be used. In addition, the amount of MVPA was negatively associated with the number of days required to identify the habitual physical activity level indicating that the least active are also those whose habitual physical activity level is the most difficult to identify. These results could have important implications for researchers whose aim is to analyse data on an individual level. Before recommendations regarding an appropriate monitoring protocol are updated, the present study should be replicated in different populations.

  • 11.
    Bonnedahl, Jonas
    et al.
    Uppsala University ; Kalmar County Hospital.
    Drobni, M
    Gauthier-Clerc, M
    Hernandez, Jorge
    Kalmar County Hospital.
    Granholm, S
    Kayser, Y
    Melhus, Å
    Kahlmeter, G
    Waldenström, Jonas
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Johansson, A
    Olsen, Björn
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Dissemination of Escherichia coli with CTX-M Type ESBL between Humans and Yellow-Legged Gulls in the South of France2009In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 4, no Article number: e5958Article in journal (Refereed)
    Abstract [en]

     Extended Spectrum beta-Lactamase (ESBL) producing Enterobacteriaceae started to appear in the 1980s, and have since emerged as some of the most significant hospital-acquired infections with Escherichia coli and Klebsiella being main players. More than 100 different ESBL types have been described, the most widespread being the CTX-M beta-lactamase enzymes (bla(CTX-M) genes). This study focuses on the zoonotic dissemination of ESBL bacteria, mainly CTX-M type, in the southern coastal region of France. We found that the level of general antibiotic resistance in single randomly selected E. coli isolates from wild Yellow-legged Gulls in France was high. Nearly half the isolates (47,1%) carried resistance to one or more antibiotics (in a panel of six antibiotics), and resistance to tetracycline, ampicillin and streptomycin was most widespread. In an ESBL selective screen, 9,4% of the gulls carried ESBL producing bacteria and notably, 6% of the gulls carried bacteria harboring CTX-M-1 group of ESBL enzymes, a recently introduced and yet the most common clinical CTX-M group in France. Multi locus sequence type and phylogenetic group designations were established for the ESBL isolates, revealing that birds and humans share E. coli populations. Several ESBL producing E. coli isolated from birds were identical to or clustered with isolates with human origin. Hence, wild birds pick up E. coli of human origin, and with human resistance traits, and may accordingly also act as an environmental reservoir and melting pot of bacterial resistance with a potential to re-infect human populations.

  • 12.
    Bonnedahl, Jonas
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science. Kalmar County Hospital.
    Stedt, Johan
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science.
    Waldenström, Jonas
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science.
    Svensson, Lovisa
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science.
    Drobni, Mirva
    Uppsala University.
    Olsen, Björn
    Uppsala University.
    Comparison of Extended-Spectrum beta-Lactamase (ESBL) CTX-M Genotypes in Franklin Gulls from Canada and Chile2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 10, article id e0141315Article in journal (Refereed)
    Abstract [en]

    Migratory birds have been suggested to contribute to long-distance dispersal of antimicrobial resistant bacteria, but tests of this hypothesis are lacking. In this study we determined resistance profiles and genotypes of ESBL-producing bacteria in randomly selected Escherichia coli from Franklin's gulls (Leucophaeus pipixcan) at breeding sites in Canada and compared with similar data from the gulls' wintering grounds in Chile. Resistant E. coli phenotypes were common, most notably to ampicillin (30.1%) and cefadroxil (15.1%). Furthermore, 17.0% of the gulls in Canada carried ESBL producing bacteria, which is higher than reported from human datasets from the same country. However, compared to gulls sampled in Chile (30.1%) the prevalence of ESBL was much lower. The dominant ESBL variants in Canada were bla(CTX-M-14) and bla(CTX-M-15) and differed in proportions to the data from Chile. We hypothesize that the observed differences in ESBL variants are more likely linked to recent exposure to bacteria from anthropogenic sources, suggesting high local dissemination of resistant bacteria both at breeding and non-breeding times rather than a significant trans-hemispheric exchange through migrating birds.

  • 13.
    Bravo, Giangiacomo
    et al.
    Linnaeus University, Faculty of Social Sciences, Department of Social Studies. Collegio Carlo Alberto, Moncalieri, Italy.
    Squazzoni, Flaminio
    University of Brescia, Italy.
    Exit, punishment and rewards in commons dilemmas: An experimental study2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 8, article id e69871Article in journal (Refereed)
    Abstract [en]

    Commons dilemmas are interaction situations where a common good is provided or exploited by a group of individuals so that optimal collective outcomes clash with private interests. Although in these situations, social norms and institutions exist that might help individuals to cooperate, little is known about the interaction effects between positive and negative incentives and exit options by individuals. We performed a modified public good game experiment to examine the effect of exit, rewards and punishment, as well as the interplay between exit and rewards and punishment. We found that punishment had a stronger effect than rewards on cooperation if considered by itself, whereas rewards had a stronger effect when combined with voluntary participation. This can be explained in terms of the `framing effect', i.e., as the combination of exit and rewards might induce people to attach higher expected payoffs to cooperative strategies and expect better behaviour from others.

  • 14.
    Buetti-Dinh, Antoine
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences. Univ Svizzera Italiana, Switzerland;Swiss Inst Bioinformat, Switzerland.
    O'Hare, Thomas
    Univ Utah, USA;Huntsman Canc Inst, USA.
    Friedman, Ran
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Sensitivity Analysis of the NPM-ALK Signalling Network Reveals Important Pathways for Anaplastic Large Cell Lymphoma Combination Therapy2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 9, article id e0163011Article in journal (Refereed)
    Abstract [en]

    A large subset of anaplastic large cell lymphoma (ALCL) patients harbour a somatic aberration in which anaplastic lymphoma kinase (ALK) is fused to nucleophosmin (NPM) resulting in a constitutively active signalling fusion protein, NPM-ALK. We computationally simulated the signalling network which mediates pathological cell survival and proliferation through NPM-ALK to identify therapeutically targetable nodes through which it may be possible to regain control of the tumourigenic process. The simulations reveal the predominant role of the VAV1-CDC42 (cell division control protein 42) pathway in NPM-ALK-driven cellular proliferation and of the Ras / mitogen-activated ERK kinase (MEK) / extracellular signal-regulated kinase (ERK) cascade in controlling cell survival. Our results also highlight the importance of a group of interleukins together with the Janus kinase 3 (JAK3) / signal transducer and activator of transcription 3 (STAT3) signalling in the development of NPM-ALK derived ALCL. Depending on the activity of JAK3 and STAT3, the system may also be sensitive to activation of protein tyrosine phosphatase-1 (SHP1), which has an inhibitory effect on cell survival and proliferation. The identification of signalling pathways active in tumourigenic processes is of fundamental importance for effective therapies. The prediction of alternative pathways that circumvent classical therapeutic targets opens the way to preventive approaches for countering the emergence of cancer resistance.

  • 15.
    Caesar, Sofia
    et al.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Karlsson, Magnus
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Forsman, Anders
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Diversity and relatedness enhance survival in colour polymorphic grasshoppers2010In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 5, no 5, article id e10880Article in journal (Refereed)
    Abstract [en]

    Evolutionary theory predicts that different resource utilization and behaviour by alternative phenotypes may reduce competition and enhance productivity and individual performance in polymorphic, as compared with monomorphic, groups of individuals. However, firm evidence that members of more heterogeneous groups benefit from enhanced survival has been scarce or lacking. Furthermore, benefits associated with phenotypic diversity may be counterbalanced by costs mediated by reduced relatedness, since closely related individuals typically are more similar. Pygmy grasshoppers (Tetrix subulata) are characterized by extensive polymorphism in colour pattern, morphology, behaviour and physiology. We studied experimental groups founded by different numbers of mothers and found that survival was higher in low than in high density, that survival peaked at intermediate colour morph diversity in high density, and that survival was independent of diversity in low density where competition was less intense. We further demonstrate that survival was enhanced by relatedness, as expected if antagonistic and competitive interactions are discriminately directed towards non-siblings. We therefore also performed behavioural observations and staged encounters which confirmed that individuals recognized and responded differently to siblings than to non-siblings. We conclude that negative effects associated with competition are less manifest in diverse groups, that there is conflicting selection for and against genetic diversity occurring simultaneously, and that diversity and relatedness may facilitate the productivity and ecological success of groups of interacting individuals.

  • 16.
    Camargo, Samia M.
    et al.
    Universidade Estadual Paulista, Brazil ; Universidade Federal de São Paulo, Brazil.
    Coelho, Rui
    Instituto Português do Mar e da Atmosfera, Portugal ; Universidade Algarve, Portugal.
    Chapman, Demian
    Stony Brook University, USA.
    Howey-Jordan, Lucy
    Microwave Telemetry, Inc., USA.
    Brooks, Edward J.
    Cape Eleuthera Institute, Bahamas.
    Fernando, Daniel
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science. The Manta Trust, UK ; Blue Resources, Sri Lanka.
    Mendes, Natalia J.
    Universidade Estadual Paulista, Brazil.
    Hazin, Fabio H. V.
    Universidade Federal Rural de Pernambuco, Brazil.
    Oliveira, Claudio
    Universidade Estadual Paulista, Brazil.
    Santos, Miguel N.
    Instituto Português do Mar e da Atmosfera, Portugal.
    Foresti, Fausto
    Universidade Estadual Paulista, Brazil.
    Mendonca, Fernando F.
    Universidade Federal de São Paulo, Brazil.
    Structure and Genetic Variability of the Oceanic Whitetip Shark, Carcharhinus longimanus, Determined Using Mitochondrial DNA2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 5, article id e0155623Article in journal (Refereed)
    Abstract [en]

    Information regarding population structure and genetic connectivity is an important contribution when establishing conservation strategies to manage threatened species. The oceanic whitetip shark, Carcharhinus longimanus, is a highly migratory, large-bodied, pelagic shark listed by the IUCN (International Union for Conservation of Nature) Red List as "vulnerable" throughout its range and "critically endangered" in the western north Atlantic. In 2014, the species was protected globally under Appendix II of CITES (Convention on International Trade in Endangered Species), limiting and regulating trade. This study used partial sequences of mitochondrial DNA (mtDNA) control region to determine the population genetic structure of oceanic whitetip sharks across the Atlantic and Indian Oceans. 724 base pairs were obtained from 215 individuals that identifed nine polymorphic sites and defined 12 distinct haplotypes. Total nucleotide diversity (pi) was 0.0013 and haplotype diversity (h) was 0.5953. The Analysis of Molecular Variance (AMOVA) evidenced moderate levels of population structure (phi(ST) = 0.1039) with restricted gene flow between the western and eastern Atlantic Ocean, and a strong relationship between the latter region and the Indian Ocean. Even though the oceanic whitetip is a highly migratory animal the results presented here show that their genetic variability is slightly below average of other pelagic sharks. Additionally, this study recommends that at least two populations in the Atlantic Ocean should be considered distinct (eastern and western Atlantic) and conservation efforts should be focused in areas with the greatest genetic diversity by environmental managers.

  • 17.
    Chapman, Joanne R.
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science.
    Helin, Anu S.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science.
    Wille, Michelle
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science. Uppsala University.
    Atterby, Clara
    Uppsala University.
    Jarhult, Josef D.
    Uppsala University.
    Fridlund, Jimmy
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science.
    Waldenström, Jonas
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science.
    A Panel of Stably Expressed Reference Genes for Real-Time qPCR Gene Expression Studies of Mallards (Anas platyrhynchos)2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 2, article id e0149454Article in journal (Refereed)
    Abstract [en]

    Determining which reference genes have the highest stability, and are therefore appropriate for normalising data, is a crucial step in the design of real-time quantitative PCR (qPCR) gene expression studies. This is particularly warranted in non-model and ecologically important species for which appropriate reference genes are lacking, such as the mallard-a key reservoir of many diseases with relevance for human and livestock health. Previous studies assessing gene expression changes as a consequence of infection in mallards have nearly universally used beta-actin and/or GAPDH as reference genes without confirming their suitability as normalisers. The use of reference genes at random, without regard for stability of expression across treatment groups, can result in erroneous interpretation of data. Here, eleven putative reference genes for use in gene expression studies of the mallard were evaluated, across six different tissues, using a low pathogenic avian influenza A virus infection model. Tissue type influenced the selection of reference genes, whereby different genes were stable in blood, spleen, lung, gastrointestinal tract and colon. beta-actin and GAPDH generally displayed low stability and are therefore inappropriate reference genes in many cases. The use of different algorithms (GeNorm and NormFinder) affected stability rankings, but for both algorithms it was possible to find a combination of two stable reference genes with which to normalise qPCR data in mallards. These results highlight the importance of validating the choice of normalising reference genes before conducting gene expression studies in ducks. The fact that nearly all previous studies of the influence of pathogen infection on mallard gene expression have used a single, non-validated reference gene is problematic. The toolkit of putative reference genes provided here offers a solid foundation for future studies of gene expression in mallards and other waterfowl.

  • 18.
    Chapman, Joanne R.
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science.
    Waldenström, Jonas
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science.
    With Reference to Reference Genes: A Systematic Review of Endogenous Controls in Gene Expression Studies2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 11, article id e0141853Article, review/survey (Refereed)
    Abstract [en]

    The choice of reference genes that are stably expressed amongst treatment groups is a crucial step in real-time quantitative PCR gene expression studies. Recent guidelines have specified that a minimum of two validated reference genes should be used for normalisation. However, a quantitative review of the literature showed that the average number of reference genes used across all studies was 1.2. Thus, the vast majority of studies continue to use a single gene, with beta-actin (ACTB) and/or glyceraldehyde 3-phosphate dehydrogenase (GAPDH) being commonly selected in studies of vertebrate gene expression. Few studies (15%) tested a panel of potential reference genes for stability of expression before using them to normalise data. Amongst studies specifically testing reference gene stability, few found ACTB or GAPDH to be optimal, whereby these genes were significantly less likely to be chosen when larger panels of potential reference genes were screened. Fewer reference genes were tested for stability in non-model organisms, presumably owing to a dearth of available primers in less well characterised species. Furthermore, the experimental conditions under which real-time quantitative PCR analyses were conducted had a large influence on the choice of reference genes, whereby different studies of rat brain tissue showed different reference genes to be the most stable. These results highlight the importance of validating the choice of normalising reference genes before conducting gene expression studies.

  • 19.
    Danielsson, Tom
    et al.
    Linnaeus University, Faculty of Social Sciences, Department of Sport Science.
    Carlsson, Jörg
    Linnaeus University, Faculty of Health and Life Sciences, Department of Health and Caring Sciences. Kalmar County Hospital.
    Schreyer, Hendrik
    Kalmar County Hospital.
    Ahnesjö, Jonas
    Linnaeus University, Faculty of Social Sciences, Department of Sport Science.
    ten Siethoff, Lasse
    Linnaeus University, Faculty of Social Sciences, Department of Sport Science.
    Ragnarsson, Thony
    Linnaeus University, Faculty of Social Sciences, Department of Sport Science.
    Tugetam, Åsa
    Linnaeus University, Faculty of Social Sciences, Department of pedagogy. Linnaeus University, Faculty of Social Sciences, Department of Sport Science.
    Bergman, Patrick
    Linnaeus University, Faculty of Social Sciences, Department of Sport Science.
    Blood biomarkers in male and female participants after an Ironman-distance triathlon2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 6, p. 1-9, article id e0179324Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: While overall physical activity is clearly associated with a better short-term and long-term health, prolonged strenuous physical activity may result in a rise in acute levels of blood-biomarkers used in clinical practice for diagnosis of various conditions or diseases. In this study, we explored the acute effects of a full Ironman-distance triathlon on biomarkers related to heart-, liver-, kidney- and skeletal muscle damage immediately post-race and after one week's rest. We also examined if sex, age, finishing time and body composition influenced the post-race values of the biomarkers.

    METHODS: A sample of 30 subjects was recruited (50% women) to the study. The subjects were evaluated for body composition and blood samples were taken at three occasions, before the race (T1), immediately after (T2) and one week after the race (T3). Linear regression models were fitted to analyse the independent contribution of sex and finishing time controlled for weight, body fat percentage and age, on the biomarkers at the termination of the race (T2). Linear mixed models were fitted to examine if the biomarkers differed between the sexes over time (T1-T3).

    RESULTS: Being male was a significant predictor of higher post-race (T2) levels of myoglobin, CK, and creatinine levels and body weight was negatively associated with myoglobin. In general, the models were unable to explain the variation of the dependent variables. In the linear mixed models, an interaction between time (T1-T3) and sex was seen for myoglobin and creatinine, in which women had a less pronounced response to the race.

    CONCLUSION: Overall women appear to tolerate the effects of prolonged strenuous physical activity better than men as illustrated by their lower values of the biomarkers both post-race as well as during recovery.

  • 20.
    Dupont, Chris L.
    et al.
    J. Craig Venter Institute, USA.
    Larsson, John
    Stockholm University.
    Yooseph, Shibu
    J. Craig Venter Institute, USA.
    Ininbergs, Karolina
    Stockholm University.
    Goll, Johannes
    J. Craig Venter Institute, USA.
    Asplund-Samuelsson, Johannes
    Stockholm University.
    McCrow, John P.
    J. Craig Venter Institute, USA.
    Celepli, Narin
    Stockholm University.
    Allen, Lisa Zeigler
    J. Craig Venter Institute, USA.
    Ekman, Martin
    Stockholm University.
    Lucas, Andrew J.
    Hagström, Åke
    University of Gothenburg.
    Thiagarajan, Mathangi
    Brindefalk, Bjorn
    Richter, Alexander R.
    Andersson, Anders F.
    Tenney, Aaron
    Lundin, Daniel
    KTH Royal Institute of Technology.
    Tovchigrechko, Andrey
    Nylander, Johan A. A.
    Brami, Daniel
    Badger, Jonathan H.
    Allen, Andrew E.
    Rusch, Douglas B.
    Hoffman, Jeff
    Norrby, Erling
    Friedman, Robert
    Pinhassi, Jarone
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science.
    Venter, J. Craig
    Bergman, Birgitta
    Functional Tradeoffs Underpin Salinity-Driven Divergence in Microbial Community Composition2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 2, article id e89549Article in journal (Refereed)
    Abstract [en]

    Bacterial community composition and functional potential change subtly across gradients in the surface ocean. In contrast, while there are significant phylogenetic divergences between communities from freshwater and marine habitats, the underlying mechanisms to this phylogenetic structuring yet remain unknown. We hypothesized that the functional potential of natural bacterial communities is linked to this striking divide between microbiomes. To test this hypothesis, metagenomic sequencing of microbial communities along a 1,800 km transect in the Baltic Sea area, encompassing a continuous natural salinity gradient from limnic to fully marine conditions, was explored. Multivariate statistical analyses showed that salinity is the main determinant of dramatic changes in microbial community composition, but also of large scale changes in core metabolic functions of bacteria. Strikingly, genetically and metabolically different pathways for key metabolic processes, such as respiration, biosynthesis of quinones and isoprenoids, glycolysis and osmolyte transport, were differentially abundant at high and low salinities. These shifts in functional capacities were observed at multiple taxonomic levels and within dominant bacterial phyla, while bacteria, such as SAR11, were able to adapt to the entire salinity gradient. We propose that the large differences in central metabolism required at high and low salinities dictate the striking divide between freshwater and marine microbiomes, and that the ability to inhabit different salinity regimes evolved early during bacterial phylogenetic differentiation. These findings significantly advance our understanding of microbial distributions and stress the need to incorporate salinity in future climate change models that predict increased levels of precipitation and a reduction in salinity.

  • 21.
    Ehrnthaller, Christian
    et al.
    University of Ulm, Germany.
    Huber-Lang, Markus
    University of Ulm, Germany.
    Nilsson, Per H.
    University of Oslo, Norway.
    Bindl, Ronny
    University of Ulm, Germany.
    Redeker, Simon
    University of Ulm, Germany.
    Recknagel, Stefan
    University of Ulm, Germany.
    Rapp, Anna
    University of Ulm, Germany.
    Mollnes, Tom
    University of Oslo, Norway.
    Amling, Michael
    Univ Med Ctr Hamburg Eppendorf, Germany.
    Gebhard, Florian
    University of Ulm, Germany.
    Ignatius, Anita
    University of Ulm, Germany.
    Complement C3 and C5 deficiency affects fracture healing.2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 11, article id UNSP e81341Article in journal (Refereed)
    Abstract [en]

    There is increasing evidence that complement may play a role in bone development. Our previous studies demonstrated that the key complement receptor C5aR was strongly expressed in the fracture callus not only by immune cells but also by bone cells and chondroblasts, indicating a function in bone repair. To further elucidate the role of complement in bone healing, this study investigated fracture healing in mice in the absence of the key complement molecules C3 and C5. C3(-/-) and C5(-/-) as well as the corresponding wildtype mice received a standardized femur osteotomy, which was stabilized using an external fixator. Fracture healing was investigated after 7 and 21 days using histological, micro-computed tomography and biomechanical measurements. In the early phase of fracture healing, reduced callus area (C3(-/-): -25%, p=0.02; C5(-/-): -20% p=0.052) and newly formed bone (C3(-/-): -38%, p=0.01; C5(-/-): -52%, p=0.009) was found in both C3- and C5-deficient mice. After 21 days, healing was successful in the absence of C3, whereas in C5-deficient mice fracture repair was significantly reduced, which was confirmed by a reduced bending stiffness (-45%; p=0.029) and a smaller callus volume (-17%; p=0.039). We further demonstrated that C5a was activated in C3(-/-) mice, suggesting cleavage via extrinsic pathways. Our results suggest that the activation of the terminal complement cascade in particular may be crucial for successful fracture healing.

  • 22.
    El Alaoui, Samir
    et al.
    Karolinska Institutet.
    Ljotsson, Brjann
    Karolinska Institutet.
    Hedman, Erik
    Karolinska Institutet.
    Kaldo, Viktor
    Karolinska Institutet.
    Andersson, Evelyn
    Karolinska Institutet.
    Rück, Christian
    Karolinska Institutet.
    Andersson, Gerhard
    Karolinska Institutet;Linköping University.
    Lindefors, Nils
    Karolinska Institutet.
    Predictors of Symptomatic Change and Adherence in Internet-Based Cognitive Behaviour Therapy for Social Anxiety Disorder in Routine Psychiatric Care2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 4, article id e0124258Article in journal (Refereed)
    Abstract [en]

    Objective A central goal of health care is to improve patient outcomes. Although several studies have demonstrated the effectiveness of therapist guided internet-based cognitive behaviour therapy (ICBT) for social anxiety disorder (SAD), a significant proportion of patients do not respond to treatment. Consequently, the aim of this study was to identify individual characteristics and treatment program related factors that could help clinicians predict treatment outcomes and adherence for individuals with SAD. Method The sample comprised longitudinal data collected during a 4-year period of adult individuals (N = 764) treated for SAD at a public service psychiatric clinic. Weekly self-rated Liebowitz Social Anxiety Scale (LSAS-SR) scores were provided. Rates of symptomatic change during treatment and adherence levels were analysed using multilevel modelling. The following domains of prognostic variables were examined: (a) socio-demographic variables; (b) clinical characteristics; (c) family history of mental illness; and (d) treatment-related factors. Results Higher treatment credibility and adherence predicted a faster rate of improvement during treatment, whereas higher overall functioning level evidenced a slower rate of improvement. Treatment credibility was the strongest predictor of greater adherence. Having a family history of SAD-like symptoms was also associated with greater adherence, whereas Attention-Deficit/Hyperactivity Disorder (ADHD)-like symptoms, male gender, and family history of minor depression predicted lower adherence. Also, the amount of therapist time spent per treatment module was negatively associated with adherence. Conclusions Results from a large clinical sample indicate that the credibility of ICBT is the strongest prognostic factor explaining individual differences in both adherence level and symptomatic improvement. Early screening of ADHD-like symptoms may help clinicians identify patients who might need extra support or an adjusted treatment. Therapist behaviours that promote adherence may be important for treatment response, although more research is needed in order to determine what type of support would be most beneficial.

  • 23.
    El Alaoui, Samir
    et al.
    Karolinska Institutet.
    Ljotsson, Brjann
    Karolinska Institutet.
    Hedman, Erik
    Karolinska Institutet.
    Svanborg, Cecilia
    Karolinska Institutet.
    Kaldo, Viktor
    Karolinska Institutet.
    Lindefors, Nils
    Karolinska Institutet.
    Predicting Outcome in Internet-Based Cognitive Behaviour Therapy for Major Depression: A Large Cohort Study of Adult Patients in Routine Psychiatric Care2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 9, article id e0161191Article in journal (Refereed)
    Abstract [en]

    Background Although the effectiveness of therapist-guided internet-based cognitive behaviour therapy (ICBT) for treating depression has been well documented, knowledge of outcome predictors and risk factors associated with lower treatment response is limited, especially when the treatment has been conducted within a naturalistic clinical setting. Identification of such factors is important for clinicians when making treatment recommendations. Methods Data from a large cohort (N = 1738) of adult outpatients having been treated with ICBT for depression at an outpatient psychiatric clinic were analysed. A multilevel modelling approach was used to identify patient and treatment variables associated with the speed of recovery during treatment using weekly measurements of the Montgomery Asberg Depression Rating Scale Self-Rated (MADRS-S). Outcomes Adhering to the treatment, perceiving it as credible and working full-time emerged as predictors of a faster pace of recovery and were also associated with a lower level of depression at the end of treatment. Higher pre-treatment depression and sleep problems were associated with a greater improvement rate, but predicted higher depression after treatment. Having a history of psychotropic medication was associated with both slower improvement and higher post-treatment depression. Conclusion Perceived credibility of ICBT is a strong predictor of treatment response. Assessing patient beliefs and expectations may be a useful aid for clinicians when identifying those who are more or less likely to benefit from ICBT. Helping patients improve expectations prior to treatment may be an important goal for clinicians during the initial assessment phase.

  • 24.
    Elfving, Karin
    et al.
    Uppsala University Hospital ; Falu Hospital.
    Olsen, Björn
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences. Uppsala University Hospital.
    Bergström, Sven
    Umeå University.
    Waldenström, Jonas
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences. Uppsala University Hospital.
    Lundkvist, Åke
    Swedish Institute for Infectious Disease Control.
    Sjöstedt, Anders
    Umeå University Hospital.
    Mejlon, Hans
    Uppsala University.
    Nilsson, Kenneth
    Uppsala University Hospital ; Falu Hospital ; Uppsala University.
    Dissemination of Spotted Fever Rickettsia Agents in Europe by Migrating Birds2010In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 5, no 1, article id e8572Article in journal (Refereed)
    Abstract [en]

    Migratory birds are known to play a role as long-distance vectors for many microorganisms. To investigate whether this is true of rickettsial agents as well, we characterized tick infestation and gathered ticks from 13,260 migratory passerine birds in Sweden. A total of 1127 Ixodes spp. ticks were removed from these birds and the extracted DNA from 957 of them was available for analyses. The DNA was assayed for detection of Rickettsia spp. using real-time PCR, followed by DNA sequencing for species identification. Rickettsia spp. organisms were detected in 108 (11.3%) of the ticks. Rickettsia helvetica, a spotted fever rickettsia associated with human infections, was predominant among the PCR-positive samples. In 9 (0.8%) of the ticks, the partial sequences of 17kDa and ompB genes showed the greatest similarity to Rickettsia monacensis, an etiologic agent of Mediterranean spotted fever-like illness, previously described in southern Europe as well as to the Rickettsia sp. IrITA3 strain. For 15 (1.4%) of the ticks, the 17kDa, ompB, gltA and ompA genes showed the greatest similarity to Rickettsia sp. strain Davousti, Rickettsia japonica and Rickettsia heilongjiangensis, all closely phylogenetically related, the former previously found in Amblyomma tholloni ticks in Africa and previously not detected in Ixodes spp. ticks. The infestation prevalence of ticks infected with rickettsial organisms was four times higher among ground foraging birds than among other bird species, but the two groups were equally competent in transmitting Rickettsia species. The birds did not seem to serve as reservoir hosts for Rickettsia spp., but in one case it seems likely that the bird was rickettsiemic and that the ticks had acquired the bacteria from the blood of the bird. In conclusion, migratory passerine birds host epidemiologically important vector ticks and Rickettsia species and contribute to the geographic distribution of spotted fever rickettsial agents and their diseases.

  • 25.
    Farnelid, Hanna
    et al.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Andersson, Anders F.
    Bertilsson, Stefan
    Al-Soud, Waleed Abu
    Hansen, Lars H
    Sørensen, Søren
    Steward, Grieg F
    Hagström, Åke
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Riemann, Lasse
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences. Marine Biological Section, Department of Biology, University of Copenhagen, Helsingør, Denmark.
    Nitrogenase gene amplicons from global marine surface waters are dominated by genes of non-cyanobacteria2011In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 6, no 4, p. e19223-Article in journal (Refereed)
    Abstract [en]

    Cyanobacteria are thought to be the main N(2)-fixing organisms (diazotrophs) in marine pelagic waters, but recent molecular analyses indicate that non-cyanobacterial diazotrophs are also present and active. Existing data are, however, restricted geographically and by limited sequencing depths. Our analysis of 79,090 nitrogenase (nifH) PCR amplicons encoding 7,468 unique proteins from surface samples (ten DNA samples and two RNA samples) collected at ten marine locations world-wide provides the first in-depth survey of a functional bacterial gene and yield insights into the composition and diversity of the nifH gene pool in marine waters. Great divergence in nifH composition was observed between sites. Cyanobacteria-like genes were most frequent among amplicons from the warmest waters, but overall the data set was dominated by nifH sequences most closely related to non-cyanobacteria. Clusters related to Alpha-, Beta-, Gamma-, and Delta-Proteobacteria were most common and showed distinct geographic distributions. Sequences related to anaerobic bacteria (nifH Cluster III) were generally rare, but preponderant in cold waters, especially in the Arctic. Although the two transcript samples were dominated by unicellular cyanobacteria, 42% of the identified non-cyanobacterial nifH clusters from the corresponding DNA samples were also detected in cDNA. The study indicates that non-cyanobacteria account for a substantial part of the nifH gene pool in marine surface waters and that these genes are at least occasionally expressed. The contribution of non-cyanobacterial diazotrophs to the global N(2) fixation budget cannot be inferred from sequence data alone, but the prevalence of non-cyanobacterial nifH genes and transcripts suggest that these bacteria are ecologically significant.

  • 26.
    Forss, Jörgen
    et al.
    Linnaeus University, Faculty of Technology, Department of Built Environment and Energy Technology.
    Lindh, Markus V.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science.
    Pinhassi, Jarone
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science.
    Welander, Ulrika
    Linnaeus University, Faculty of Technology, Department of Built Environment and Energy Technology.
    Microbial biotreatment of actual textile wastewater in a continuous sequential rice husk biofilter and the microbial community involved2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 1, article id e0170562Article in journal (Refereed)
    Abstract [en]

    Textile dying processes often pollute wastewater with recalcitrant azo and anthraquinone dyes. Yet, there is little development of effective and affordable degradation systems for textile wastewater applicable in countries where water technologies remain poor. We determined biodegradation of actual textile wastewater in biofilters containing rice husks by spectrophotometry and liquid chromatography mass spectrometry. The indigenous microflora from the rice husks consistently performed >90% decolorization at a hydraulic retention time of 67 h. Analysis of microbial community composition of bacterial 16S rRNA genes and fungal internal transcribed spacer (ITS) gene fragments in the biofilters revealed a bacterial consortium known to carry azoreductase genes, such as Dysgonomonas, and Pseudomonas and the presence of fungal phylotypes such as Gibberella and Fusarium. Our findings emphasize that rice husk biofilters support a microbial community of both bacteria and fungi with key features for biodegradation of actual textile wastewater. These results suggest that microbial processes can substantially contribute to efficient and reliable degradation of actual textile wastewater. Thus, development of biodegradation systems holds promise for application of affordable wastewater treatment in polluted environments.

  • 27.
    Franzén, Markus
    et al.
    Helmholtz Centre for Environmental Research, Germany ; Lund University.
    Schweiger, Oliver
    Helmholtz Centre for Environmental Research, Germany.
    Betzholtz, Per-Eric
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Species-area relationships are controlled by species traits2012In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 5, article id e37359Article in journal (Refereed)
    Abstract [en]

    The species-area relationship (SAR) is one of the most thoroughly investigated empirical relationships in ecology. Two theories have been proposed to explain SARs: classical island biogeography theory and niche theory. Classical island biogeography theory considers the processes of persistence, extinction, and colonization, whereas niche theory focuses on species requirements, such as habitat and resource use. Recent studies have called for the unification of these two theories to better explain the underlying mechanisms that generates SARs. In this context, species traits that can be related to each theory seem promising. Here we analyzed the SARs of butterfly and moth assemblages on islands differing in size and isolation. We tested whether species traits modify the SAR and the response to isolation. In addition to the expected overall effects on the area, traits related to each of the two theories increased the model fit, from 69% up to 90%. Steeper slopes have been shown to have a particularly higher sensitivity to area, which was indicated by species with restricted range (slope  = 0.82), narrow dietary niche (slope  = 0.59), low abundance (slope  = 0.52), and low reproductive potential (slope  = 0.51). We concluded that considering species traits by analyzing SARs yields considerable potential for unifying island biogeography theory and niche theory, and that the systematic and predictable effects observed when considering traits can help to guide conservation and management actions.

  • 28. Frick, Jerker
    et al.
    Lindberg, Richard
    Tysklind, Mats
    Haemig, Paul
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Waldenström, Jonas
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Wallensten, Anders
    Olsen, Björn
    University of Kalmar, School of Pure and Applied Natural Sciences.
    Anitiviral Oseltamivir is not removed or degraded in normal sewage ater treatment: implications for the develoment of resitance by influenza A virus2007In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 2, no 10Article in journal (Refereed)
  • 29.
    Friedman, Ran
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    Drug Resistance Missense Mutations in Cancer Are Subject to Evolutionary Constraints2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 12, article id e82059Article in journal (Refereed)
    Abstract [en]

    Several tumor types are sensitive to deactivation of just one or very few genes that are constantly active in the cancer cells,a phenomenon that is termed oncogene addiction'. Drugs that target the products of those oncogenes can yield a temporary relief, and even complete remission. Unfortunately, many patients receiving oncogene-targeted therapies relapse on treatment. This often happens due to somatic mutations in the oncogene (resistance mutations"). 'Compound mutations', which in the context of cancer drug resistance are defined as two or more mutations of the drug target in the same clone may lead to enhanced resistance against the most selective inhibitors. Here, it is shown that the vast majority the resistance mutations occurring in cancer patients treated with tyrosin kinase inhibitors aimed at three different proteins follow an evolutionary pathway. Using bioinforrnatic analysis tools, found that the drug-resistance mutations in the tyrosine kinase domains of Abl1, ALK and exons 20 and 21 of EGFR favour transformations to residues that can be identified in similar positions in evolutionary related proteins. The results demonstrate that evolutionary pressure shapes the mutational landscape in the case of drug-resistance somatic mutations. The constraints on the mutational landscape suggest that it may be possible to counter single drug-resistance point mutations. The observation of relatively many resistance mutations in Abl1, but not in the other genes, is explained by the fact that mutations in Abl1 tend to be biochemically conservative, whereas mutations in EGFR and ALK tend to be radical. Analysis of Abl1 compound mutations suggests that such mutations are more prevalent than hitherto reported and may be more difficult to counter. This supports the notion that such mutations may provide an escape route for targeted cancer drug resistance.

  • 30.
    Garbarini, Francesca
    et al.
    Univ Turin, Italy.
    Riccardo, Boero
    Los Alamos Natl Lab, USA.
    Francesco, D'Agata
    Univ Turin, Italy.
    Bravo, Giangiacomo
    Linnaeus University, Faculty of Social Sciences, Department of Social Studies.
    Cristina, Mosso
    Univ Turin, Italy.
    Franco, Cauda
    Univ Turin, Italy.
    Sergio, Duca
    Koelliker Hosp, CCS FMRI, Turin, Italy.
    Giuliano, Geminiani
    Univ Turin, Italy.
    Katiuscia, Sacco
    Univ Turin, Italy.
    Neural Correlates of Gender Differences in Reputation Building2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 9, p. e106285-Article in journal (Refereed)
    Abstract [en]

    Gender differences in cooperative choices and their neural correlates were investigated in a situation where reputation represented a crucial issue. Males and females were involved in an economic exchange (trust game) where economic and reputational payoffs had to be balanced in order to increase personal welfare. At the behavioral level, females showed a stronger reaction to negative reputation judgments that led to higher cooperation than males, measured by back transfers in the game. The neuroanatomical counterpart of this gender difference was found within the reward network (engaged in producing expectations of positive results) and reputation-related brain networks, such as the self-control network (engaged in strategically resisting the temptation to defect) and the mentalizing network (engaged in thinking about how one is viewed by others), in which the dorsolateral prefrontal cortex (DLPFC) and the medial (M)PFC respectively play a crucial role. Furthermore, both DLPFC and MPFC activity correlated with the amount of back transfer, as well as with the personality dimensions assessed with the Big-Five Questionnaire (BFQ-2). Males, according to their greater DLPFC recruitment and their higher level of the BFQ-2 subscale of Dominance, were more focused on implementing a profit-maximizing strategy, pursuing this target irrespectively of others' judgments. On the contrary, females, according to their greater MPFC activity and their lower level of Dominance, were more focused on the reputation per se and not on the strategic component of reputation building. These findings shed light on the sexual dimorphism related to cooperative behavior and its neural correlates.

  • 31.
    Gargano, Francesco
    et al.
    University of Palermo, Italy.
    Tamburino, Lucia
    Linnaeus University, Faculty of Technology, Department of Mathematics.
    Bagarello, Fabio
    University of Palermo, Italy ; INFN National Institute for Nuclear Physics, Italy.
    Bravo, Giangiacomo
    Linnaeus University, Faculty of Social Sciences, Department of Social Studies.
    Large-scale effects of migration and conflict in pre-agricultural groups: Insights from a dynamic model2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 3, article id e0172262Article in journal (Refereed)
    Abstract [en]

    The debate on the causes of conflict in human societies has deep roots. In particular, the extent of conflict in hunter-gatherer groups remains unclear. Some authors suggest that large-scale violence only arose with the spreading of agriculture and the building of complex societies. To shed light on this issue, we developed a model based on operatorial techniques simulating population-resource dynamics within a two-dimensional lattice, with humans and natural resources interacting in each cell of the lattice. The model outcomes under different conditions were compared with recently available demographic data for prehistoric South America. Only under conditions that include migration among cells and conflict was the model able to consistently reproduce the empirical data at a continental scale. We argue that the interplay between resource competition, migration, and conflict drove the population dynamics of South America after the colonization phase and before the introduction of agriculture. The relation between population and resources indeed emerged as a key factor leading to migration and conflict once the carrying capacity of the environment has been reached.

  • 32.
    Gillman, Anna
    et al.
    Uppsala University.
    Muradrasoli, Shaman
    Swedish University of Agricultural Sciences.
    Mardnas, Andreas
    Uppsala University.
    Söderström, Hanna
    Umeå University.
    Fedorova, Ganna
    Umeå University;University of South Bohemia in Ceske Budejovice, Czech Republic.
    Lowenthal, Max
    Uppsala University.
    Wille, Michelle
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science.
    Daggfeldt, Annika
    National Veterinary Institute.
    Jarhult, Josef D.
    Uppsala University.
    Oseltamivir Resistance in Influenza A(H6N2) Caused by an R292K Substitution in Neuraminidase Is Not Maintained in Mallards without Drug Pressure2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 9, article id e0139415Article in journal (Refereed)
    Abstract [en]

    Background Wild waterfowl is the natural reservoir of influenza A virus (IAV); hosted viruses are very variable and provide a source for genetic segments which can reassort with poultry or mammalian adapted IAVs to generate novel species crossing viruses. Additionally, wild waterfowl act as a reservoir for highly pathogenic IAVs. Exposure of wild birds to the antiviral drug oseltamivir may occur in the environment as its active metabolite can be released from sewage treatment plants to river water. Resistance to oseltamivir, or to other neuraminidase inhibitors (NAIs), in IAVs of wild waterfowl has not been extensively studied. Aim and Methods In a previous in vivo Mallard experiment, an influenza A(H6N2) virus developed oseltamivir resistance by the R292K substitution in the neuraminidase (NA), when the birds were exposed to oseltamivir. In this study we tested if the resistance could be maintained in Mallards without drug exposure. Three variants of resistant H6N2/R292K virus were each propagated during 17 days in five successive pairs of naive Mallards, while oseltamivir exposure was decreased and removed. Daily fecal samples were analyzed for viral presence, genotype and phenotype. Results and Conclusion Within three days without drug exposure no resistant viruses could be detected by NA sequencing, which was confirmed by functional NAI sensitivity testing. We conclude that this resistant N2 virus could not compete in fitness with wild type subpopulations without oseltamivir drug pressure, and thus has no potential to circulate among wild birds. The results of this study contrast to previous observations of drug induced resistance in an avian H1N1 virus, which was maintained also without drug exposure in Mallards. Experimental observations on persistence of NAI resistance in avian IAVs resemble NAI resistance seen in human IAVs, in which resistant N2 subtypes do not circulate, while N1 subtypes with permissive mutations can circulate without drug pressure. We speculate that the phylogenetic group N1 NAs may easier compensate for NAI resistance than group N2 NAs, though further studies are needed to confirm such conclusions.

  • 33.
    Gillman, Anna
    et al.
    Uppsala University.
    Muradrasoli, Shaman
    Swedish University of Agricultural Sciences.
    Söderstrom, Hanna
    Umeå University.
    Nordh, Johan
    Uppsala University.
    Bröjer, Caroline
    Swedish University of Agricultural Sciences.
    Lindberg, Richard H.
    Umeå University.
    Latorre-Margalef, Neus
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science.
    Waldenström, Jonas
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science.
    Olsen, Björn
    Uppsala University.
    Järhult, Josef D.
    Uppsala University.
    Resistance Mutation R292K Is Induced in Influenza A(H6N2) Virus by Exposure of Infected Mallards to Low Levels of Oseltamivir2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 8, article id e71230Article in journal (Refereed)
    Abstract [en]

    Resistance to neuraminidase inhibitors (NAIs) is problematic as these drugs constitute the major treatment option for severe influenza. Extensive use of the NAI oseltamivir (Tamiflu(R)) results in up to 865 ng/L of its active metabolite oseltamivir carboxylate (OC) in river water. There one of the natural reservoirs of influenza A, dabbling ducks, can be exposed. We previously demonstrated that an influenza A(H1N1) virus in mallards (Anas platyrhynchos) exposed to 1 mu g/L of OC developed oseltamivir resistance through the mutation H274Y (N2-numbering). In this study, we assessed the resistance development in an A(H6N2) virus, which belongs to the phylogenetic N2 group of neuraminidases with distinct functional and resistance characteristics. Mallards were infected with A(H6N2) while exposed to 120 ng/L, 1.2 mu g/L or 12 mu g/L of OC in their sole water source. After 4 days with 12 mu g/L of OC exposure, the resistance mutation R292K emerged and then persisted. Drug sensitivity was decreased approximate to 13,000-fold for OC and approximate to 7.8-fold for zanamivir. Viral shedding was similar when comparing R292K and wild-type virus indicating sustained replication and transmission. Reduced neuraminidase activity and decrease in recovered virus after propagation in embryonated hen eggs was observed in R292K viruses. The initial, but not the later R292K isolates reverted to wild-type during egg-propagation, suggesting a stabilization of the mutation, possibly through additional mutations in the neuraminidase (D113N or D141N) or hemagglutinin (E216K). Our results indicate a risk for OC resistance development also in a N2 group influenza virus and that exposure to one NAI can result in a decreased sensitivity to other NAIs as well. If established in influenza viruses circulating among wild birds, the resistance could spread to humans via re-assortment or direct transmission. This could potentially cause an oseltamivir-resistant pandemic; a serious health concern as preparedness plans rely heavily on oseltamivir before vaccines can be mass-produced.

  • 34.
    Gunnarsson, Gunnar
    et al.
    Kristianstad University.
    Latorre-Margalef, Neus
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Hobson, K. A.
    Environment Canada, Saskatoon, Canada.
    Van Wilgenburg, S. L.
    Environment Canada, Saskatoon, Canada.
    Elmberg, Johan
    Kristianstad University.
    Olsen, Björn
    Uppsala University Hospital.
    Fouchier, R. A. M.
    Erasmus Medical Center, The Netherlands.
    Waldenström, Jonas
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Disease Dynamics and Bird Migration – Linking Mallards Anas platyrhynchos and subtype diversity of Influenza A Virus in Time and Space2012In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, no 4, article id e35679Article in journal (Refereed)
    Abstract [en]

    The mallard Anas platyrhynchos is a reservoir species for influenza A virus in the northern hemisphere, with particularly high prevalence rates prior to as well as during its prolonged autumn migration. It has been proposed that the virus is brought from the breeding grounds and transmitted to conspecifics during subsequent staging during migration, and so a better understanding of the natal origin of staging ducks is vital to deciphering the dynamics of viral movement pathways. Ottenby is an important stopover site in southeast Sweden almost halfway downstream in the major Northwest European flyway, and is used by millions of waterfowl each year. Here, mallards were captured and sampled for influenza A virus infection, and positive samples were subtyped in order to study possible links to the natal area, which were determined by a novel approach combining banding recovery data and isotopic measurements (d2 H) of feathers grown on breeding grounds. Geographic assignments showed that the core natal areas of studied mallards were in Estonia, southern and central Finland, and northwestern Russia. This study demonstrates a clear temporal succession of latitudes of natal origin during the course of autumn migration. We also demonstrate a corresponding and concomitant shift in virus subtypes. Acknowledging that these two different patterns were based in part upon different data, a likely interpretation worth further testing is that the early arriving birds with more proximate origins have different influenza A subtypes than the more distantly originating late autumn birds. If true, this knowledge would allow novel insight into the origins and transmission of the influenza A virus among migratory hosts previously unavailable through conventional approaches.

  • 35.
    Guo, Ming
    et al.
    Zhejiang Agr & Forestry Univ, Peoples R China.
    Wang, Xiaomeng
    Zhejiang Agr & Forestry Univ, Peoples R China.
    Lu, Xiaowang
    Zhejiang Agr & Forestry Univ, Peoples R China.
    Wang, Hongzheng
    Zhejiang Agr & Forestry Univ, Peoples R China.
    Brodelius, Peter E.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Chemistry and Biomedical Sciences.
    alpha-Mangostin Extraction from the Native Mangosteen (Garcinia mangostana L.) and the Binding Mechanisms of alpha-Mangostin to HSA or TRF2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 9, article id e0161566Article in journal (Refereed)
    Abstract [en]

    In order to obtain the biological active compound, alpha-mangostin, from the traditional native mangosteen (Garcinia mangostana L.), an extraction method for industrial application was explored. A high yield of a-mangostin (5.2%) was obtained by extraction from dried mangosteen pericarps with subsequent purification on macroporous resin HPD-400. The chemical structure of alpha-mangostin was verified mass spectrometry (MS), nuclear magnetic resonance (H-1 NMR and C-13 NMR), infrared spectroscopy (IR) and UV-Vis spectroscopy. The purity of the obtained alpha-mangostin was 95.6% as determined by HPLC analysis. The binding of native alpha-mangostin to human serum albumin (HSA) or transferrin (TRF) was explored by combining spectral experiments with molecular modeling. The results showed that amangostin binds to HSA or TRF as static complexes but the binding affinities were different in different systems. The binding constants and thermodynamic parameters were measured by fluorescence spectroscopy and absorbance spectra. The association constant of HSA or TRF binding to alpha-mangostin is 6.4832x10(5) L/mol and 1.4652x10(5) L/mol at 298 K and 7.8619x10(5) L/mol and 1.1582x10(5) L/mol at 310 K, respectively. The binding distance, the energy transfer efficiency between alpha-mangostin and HSA or TRF were also obtained by virtue of the Forster theory of non-radiation energy transfer. The effect of alpha-mangostin on the HSA or TRF conformation was analyzed by synchronous spectrometry and fluorescence polarization studies. Molecular docking results reveal that the main interaction between amangostin and HSA is hydrophobic interactions, while the main interaction between alpha-mangostin and TRF is hydrogen bonding and Van der Waals forces. These results are consistent with spectral results.

  • 36.
    Halcox, Julian P.
    et al.
    Swansea University College of Medicine, UK.
    Tubach, Florence
    INSERM, France ; Paris Diderot University, France.
    Lopez-Garcia, Esther
    Universidad Autónoma de Madrid, Spain ; CIBERESP, Spain.
    De Backer, Guy
    University of Ghent, Belgium.
    Borghi, Claudio
    University of Bologna, Italy.
    Dallongeville, Jean
    Université Lille-Nord de France, France.
    Guallar, Eliseo
    Johns Hopkins Bloomberg School of Public Health, USA ; National Center for Cardiovascular Research, Spain.
    Medina, Jesús
    AstraZeneca Farmacéutica Spain, Spain.
    Perk, Joep
    Linnaeus University, Faculty of Health and Life Sciences, Department of Health and Caring Sciences.
    Sazova, Oguen
    AstraZeneca Global Medical Affairs, UK.
    Sweet, Stephen
    Oxford PharmaGenesis Ltd, UK.
    Roy, Carine
    INSERM, France ; Hôpital Bichat-Claude Bernard, France.
    Banegas, José R.
    Universidad Autónoma de Madrid, Spain ; CIBERESP, Spain.
    Rodriguez-Artalejo, Fernando
    Universidad Autónoma de Madrid, Spain ; CIBERESP, Spain.
    Low Rates of Both Lipid-Lowering Therapy Use and Achievement of Low-Density Lipoprotein Cholesterol Targets in Individuals at High-Risk for Cardiovascular Disease across Europe2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 2, article id e0115270Article in journal (Refereed)
    Abstract [en]

    Aims To analyse the treatment and control of dyslipidaemia in patients at high and very high cardiovascular risk being treated for the primary prevention of cardiovascular disease (CVD) in Europe. Methods and Results Data were assessed from the European Study on Cardiovascular Risk Prevention and Management in Usual Daily Practice (EURIKA, ClinicalTrials.gov identifier: NCT00882336), which included a randomly sampled population of primary CVD prevention patients from 12 European countries (n = 7641). Patients' 10-year risk of CVD-related mortality was calculated using the Systematic Coronary Risk Evaluation (SCORE) algorithm, identifying 5019 patients at high cardiovascular risk (SCORE >= 5% and/or receiving lipid-lowering therapy), and 2970 patients at very high cardiovascular risk (SCORE >= 10% or with diabetes mellitus). Among high-risk individuals, 65.3% were receiving lipid-lowering therapy, and 61.3% of treated patients had uncontrolled low-density lipoprotein cholesterol (LDL-C) levels (>= 2.5 mmol/L). For very-high-risk patients (uncontrolled LDL-C levels defined as >= 1.8 mmol/L) these figures were 49.5% and 82.9%, respectively. Excess 10-year risk of CVD-related mortality (according to SCORE) attributable to lack of control of dyslipidaemia was estimated to be 0.72% and 1.61% among high-risk and very-high-risk patients, respectively. Among high-risk individuals with uncontrolled LDL-C levels, only 8.7% were receiving a high-intensity statin (atorvastatin >= 40 mg/day or rosuvastatin >= 20 mg/day). Among very-high-risk patients, this figure was 8.4%. Conclusions There is a considerable opportunity for improvement in rates of lipid-lowering therapy use and achievement of lipid-level targets in high-risk and very-high-risk patients being treated for primary CVD prevention in Europe.

  • 37.
    Hamad, Osama A.
    et al.
    Uppsala University.
    Nilsson, Per H.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Lasaosa, Maria
    University of Pennsylvania, USA.
    Ricklin, Daniel
    University of Pennsylvania, USA.
    Lambris, John D.
    University of Pennsylvania, USA.
    Nilsson, Bo
    Uppsala University.
    Nilsson Ekdahl, Kristina
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences. Uppsala University.
    Contribution of Chondroitin Sulfate A to the Binding of Complement Proteins to Activated Platelets2010In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 5, no 9, article id e12889Article in journal (Refereed)
    Abstract [en]

    Background: Exposure of chondroitin sulfate A (CS-A) on the surface of activated platelets is well established. The aim of the present study was to investigate to what extent CS-A contributes to the binding of the complement recognition molecule C1q and the complement regulators C1 inhibitor (C1INH), C4b-binding protein (C4BP), and factor H to platelets.Principal Findings: Human blood serum was passed over Sepharose conjugated with CS-A, and CS-A-specific binding proteins were identified by Western blotting and mass spectrometric analysis. C1q was shown to be the main protein that specifically bound to CS-A, but C4BP and factor H were also shown to interact. Binding of C1INH was dependent of the presence of C1q and then not bound to CS-A from C1q-depleted serum. The specific interactions observed of these proteins with CS-A were subsequently confirmed by surface plasmon resonance analysis using purified proteins. Importantly, C1q, C4BP, and factor H were also shown to bind to activated platelets and this interaction was inhibited by a CS-A-specific monoclonal antibody, thereby linking the binding of C1q, C4BP, and factor H to exposure of CS-A on activated platelets. CS-A-bound C1q was also shown to amplify the binding of model immune complexes to both microtiter plate-bound CS-A and to activated platelets.

    Conclusions: This study supports the concept that CS-A contributes to the binding of C1q, C4BP, and factor H to platelets, thereby adding CS-A to the previously reported binding sites for these proteins on the platelet surface. CS-A-bound C1q also seems to amplify the binding of immune complexes to activated platelets, suggesting a role for this molecule in immune complex diseases. 

  • 38.
    Hao, Meng-Shu
    et al.
    Lund Univ.
    Jensen, Anna M.
    Linnaeus University, Faculty of Technology, Department of Forestry and Wood Technology. Lund Univ.
    Boquist, Ann-Sofie
    Lund Univ.
    Liu, Yun-Jun
    Lund Univ ; Chinese Acad Agr Sci, Peoples R China.
    Rasmusson, Allan G.
    Lund Univ.
    The Ca2+-Regulation of the Mitochondrial External NADPH Dehydrogenase in Plants Is Controlled by Cytosolic pH2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 9, article id e0139224Article in journal (Refereed)
    Abstract [en]

    NADPH is a key reductant carrier that maintains internal redox and antioxidant status, and that links biosynthetic, catabolic and signalling pathways. Plants have a mitochondrial external NADPH oxidation pathway, which depends on Ca2+ and pH in vitro, but concentrations of Ca2+ needed are not known. We have determined the K-0.5(Ca2+) of the external NADPH dehydrogenase from Solanum tuberosum mitochondria and membranes of E. coli expressing Arabidopsis thaliana NDB1 over the physiological pH range using O-2 and decylubiquinone as electron acceptors. The K-0.5(Ca2+) of NADPH oxidation was generally higher than for NADH oxidation, and unlike the latter, it depended on pH. At pH 7.5, K-0.5(Ca2+) for NADPH oxidation was high (approximate to 100 mu M), yet 20-fold lower K-0.5(Ca2+) values were determined at pH 6.8. Lower K-0.5(Ca2+) values were observed with decylubiquinone than with O-2 as terminal electron acceptor. NADPH oxidation responded to changes in Ca2+ concentrations more rapidly than NADH oxidation did. Thus, cytosolic acidification is an important activator of external NADPH oxidation, by decreasing the Ca2+-requirements for NDB1. The results are discussed in relation to the present knowledge on how whole cell NADPH redox homeostasis is affected in plants modified for the NDB1 gene.

  • 39.
    Hernandez, Jorge
    et al.
    Uppsala University.
    Johansson, Anders
    Umeå University.
    Stedt, Johan
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science.
    Bengtsson, Stina
    Central Hospital Växjö.
    Porczak, Aleksandra
    Central Hospital Växjö.
    Granholm, Susanne
    Umeå University.
    Gonzalez-Acuna, Daniel
    Universidad de Concepción, Chile.
    Olsen, Björn
    Uppsala University.
    Bonnedahl, Jonas
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science. Kalmar County Hospital.
    Drobni, Mirva
    Uppsala University.
    Characterization and Comparison of Extended-Spectrum beta-Lactamase (ESBL) Resistance Genotypes and Population Structure of Escherichia coli Isolated from Franklin's Gulls (Leucophaeus pipixcan) and Humans in Chile2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 9, article id e76150Article in journal (Refereed)
    Abstract [en]

    We investigated the general level of antibiotic resistance with further analysis of extended-spectrum beta-lactamase (ESBL) prevalence, as well as the population structure of E. coli in fecal flora of humans and Franklin's gulls (Leucophaeus pipixcan) in central parts of Chile. We found a surprisingly high carriage rate of ESBL-producing E. coli among the gulls 112/372 (30.1%) as compared to the human population 6/49 (12.2%.) Several of the E. coli sequence types (STs) identified in birds have previously been reported as Multi Drug Resistant (MDR) human pathogens including the ability to produce ESBLs. This means that not only commensal flora is shared between birds and humans but also STs with pathogenic potential. Given the migratory behavior of Franklin's gulls, they and other migratory species, may be a part of ESBL dissemination in the environment and over great geographic distances. Apart from keeping the antibiotic use low, breaking the transmission chains between the environment and humans must be a priority to hinder the dissemination of resistance.

  • 40.
    Huang, Yanyan
    et al.
    Department of Biology, Memorial University of Newfoundland, St. John’s, Newfoundland and Labrador, Canada.
    Wille, Michelle
    Department of Biology, Memorial University of Newfoundland, St. John’s, Newfoundland and Labrador, Canada.
    Dobbin, Ashley
    Department of Biology, Memorial University of Newfoundland, St. John’s, Newfoundland and Labrador, Canada.
    Walzthöni, Natasha M
    Department of Biology, Memorial University of Newfoundland, St. John’s, Newfoundland and Labrador, Canada.
    Robertson, Gregory J
    2 Wildlife Research Division, Environment Canada, Mount Pearl, Newfoundland and Labrador, Canada.
    Ojkic, Davor
    Animal Health Laboratory, University of Guelph, Guelph, Ontario, Canada.
    Whitney, Hugh
    Newfoundland and Labrador Department of Natural Resources, St. John’s, Newfoundland and Labrador, Canada.
    Lang, Andrew S
    Department of Biology, Memorial University of Newfoundland, St. John’s, Newfoundland and Labrador, Canada.
    Genetic structure of avian influenza viruses from ducks of the Atlantic flyway of North America.2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 1, p. Article ID: e86999-Article in journal (Refereed)
    Abstract [en]

    Wild birds, including waterfowl such as ducks, are reservoir hosts of influenza A viruses. Despite the increased number of avian influenza virus (AIV) genome sequences available, our understanding of AIV genetic structure and transmission through space and time in waterfowl in North America is still limited. In particular, AIVs in ducks of the Atlantic flyway of North America have not been thoroughly investigated. To begin to address this gap, we analyzed 109 AIV genome sequences from ducks in the Atlantic flyway to determine their genetic structure and to document the extent of gene flow in the context of sequences from other locations and other avian and mammalian host groups. The analyses included 25 AIVs from ducks from Newfoundland, Canada, from 2008-2011 and 84 available reference duck AIVs from the Atlantic flyway from 2006-2011. A vast diversity of viral genes and genomes was identified in the 109 viruses. The genetic structure differed amongst the 8 viral segments with predominant single lineages found for the PB2, PB1 and M segments, increased diversity found for the PA, NP and NS segments (2, 3 and 3 lineages, respectively), and the highest diversity found for the HA and NA segments (12 and 9 lineages, respectively). Identification of inter-hemispheric transmissions was rare with only 2% of the genes of Eurasian origin. Virus transmission between ducks and other bird groups was investigated, with 57.3% of the genes having highly similar (≥99% nucleotide identity) genes detected in birds other than ducks. Transmission between North American flyways has been frequent and 75.8% of the genes were highly similar to genes found in other North American flyways. However, the duck AIV genes did display spatial distribution bias, which was demonstrated by the different population sizes of specific viral genes in one or two neighbouring flyways compared to more distant flyways.

  • 41.
    Hugerth, Luisa W.
    et al.
    KTH Royal Institute of Technology.
    Muller, Emilie E. L.
    University of Luxembourg, Luxembourg.
    Hu, Yue O. O.
    KTH Royal Institute of Technology.
    Lebrun, Laura A. M.
    University of Luxembourg, Luxembourg.
    Roume, Hugo
    University of Luxembourg, Luxembourg.
    Lundin, Daniel
    Stockholm University.
    Wilmes, Paul
    University of Luxembourg, Luxembourg.
    Andersson, Anders F.
    KTH Royal Institute of Technology.
    Systematic Design of 18S rRNA Gene Primers for Determining Eukaryotic Diversity in Microbial Consortia2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 4, article id e95567Article in journal (Refereed)
    Abstract [en]

    High-throughput sequencing of ribosomal RNA gene (rDNA) amplicons has opened up the door to large-scale comparative studies of microbial community structures. The short reads currently produced by massively parallel sequencing technologies make the choice of sequencing region crucial for accurate phylogenetic assignments. While for 16S rDNA, relevant regions have been well described, no truly systematic design of 18S rDNA primers aimed at resolving eukaryotic diversity has yet been reported. Here we used 31,862 18S rDNA sequences to design a set of broad-taxonomic range degenerate PCR primers. We simulated the phylogenetic information that each candidate primer pair would retrieve using paired- or single-end reads of various lengths, representing different sequencing technologies. Primer pairs targeting the V4 region performed best, allowing discrimination with paired-end reads as short as 150 bp (with 75% accuracy at genus level). The conditions for PCR amplification were optimised for one of these primer pairs and this was used to amplify 18S rDNA sequences from isolates as well as from a range of environmental samples which were then Illumina sequenced and analysed, revealing good concordance between expected and observed results. In summary, the reported primer sets will allow minimally biased assessment of eukaryotic diversity in different microbial ecosystems.

  • 42.
    Huus, Karina
    et al.
    Jönköping University.
    Åkerman, Linda
    Linköping University.
    Raustorp, Anders
    Linnaeus University, Faculty of Social Sciences, Department of Sport Science. University of Gothenburg.
    Ludvigsson, Johnny
    Linköping University ; Linköping City Council.
    Physical Activity, Blood Glucose and C-Peptide in Healthy School-Children, a Longitudinal Study2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 6, article id e0156401Article in journal (Refereed)
    Abstract [en]

    Aim To further elucidate the relationship between physical activity and several risk factors for development of diabetes (glucose, C-peptide and obesity) over time. Methods A prospective longitudinal study where physical activity was measured on 199 children from Kalmar and Linkoping at age 8, and the same 107 children from Linkoping again at age 12. Anthropometric data was collected and blood was analyzed for C-peptide and f-glucose. The children in the study were representative for the general Swedish child population, and on an average lean. Results High physical activity was related to lower C-peptide at age 8 and 12. This correlation was especially pronounced in boys, who also were more physically active than girls at both time points. The association seen at 8 years of age was similar at age 12 in most children. Children with higher BMI Z-Score had a higher fasting C-peptide (age 12) but linear regression showed that children with more steps per day were less likely to have a higher fasting C-peptide irrespective of BMI. Longitudinal follow-up showed that a decrease in physical activity increased insulin resistance and beta-cell load. Conclusions Already in young children, physical activity improves insulin sensitivity and decreases the need of C-peptide over time. This seems to become even more pronounced with increasing age when children are followed longitudinally. Low physical activity increases the load on insulin producing beta-cells, might increase the risk for both type 1- and 2 diabetes.

  • 43.
    Håkansson, Krister
    et al.
    Karolinska Institutet.
    Soininen, Hilkka
    Eastern University of Finland.
    Winblad, Bengt
    Kivipelto, Miia
    Karolinska Institutet.
    Feelings of Hopelessness in Midlife and Cognitive Health in Later Life: A Prospective Population-Based Cohort Study.2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 10, p. 1-16, article id e0140261Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Several studies have found depression and depressive feelings to be associated with subsequent dementia. As dementias typically have a long preclinical development phase, it has been difficult to determine whether depression and depressive feelings reflect a concurrent underlying dementia disease, rather than playing a causative role. Our aim was to investigate hopelessness, one dimension of depressive feelings, and evaluate the likelihood of a prodromal versus a causative role of hopelessness feelings in dementia development.

    METHODS: We invited a random sample of 2000 survivors from a representative population in Eastern Finland, originally investigated in midlife between 1972 and 1987, for re-examination an average of 21 years later. The age of the 1449 persons who accepted the invitation was between 39 and 64 years (mean 50.4 years) in midlife and between 65 and 80 (mean 71.3) at follow-up. To measure feelings of hopelessness in midlife and at follow-up, the participants indicated their level of agreement to two statements about their own possible future. We used logistic regression to investigate the association between the combined scores from these two items and cognitive health at follow-up, while adjusting for several health and life-style variables from midlife and for apolipoprotein E4 (ApoE4) status, depression and hopelessness feelings at follow-up. We compared the associations with late-life cognitive health when feelings of hopelessness were either measured in midlife or at the follow-up. In addition we analyzed the changes in hopelessness scores from midlife to follow-up in participants who were either cognitively healthy or impaired at follow-up.

    RESULTS: We found higher levels of hopelessness in midlife, but not at follow-up, to be associated with cognitive impairment at follow-up; the adjusted odds ratio for each step of the five-level hopelessness scale was 1.30 (95% confidence interval 1.11-1.51) for any cognitive impairment and 1.37 (1.05-1.78) for Alzheimer's disease. These associations remained significant also after the final adjustments for depressive feelings and for hopelessness at follow-up. The individual changes in hopelessness scores between midlife and follow-up were not systematically related to cognitive health at the follow-up.

    CONCLUSION: Our results suggest that feelings of hopelessness already in midlife may have long-term implications for cognitive health and increase the risk of Alzheimer's disease in later life.

  • 44.
    Högberg, Anders
    et al.
    Linnaeus University, Faculty of Arts and Humanities, Department of Cultural Sciences. University of Johannesburg, South Africa ; Stellenbosch University, South Africa.
    Lombard, Marlize
    University of Johannesburg, South Africa ; Stellenbosch University, South Africa.
    Still Bay Point-Production Strategies at Hollow Rock Shelter and Umhlatuzana Rock Shelter and Knowledge-Transfer Systems in Southern Africa at about 80-70 Thousand Years Ago2016In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 11, no 12, article id e0168012Article in journal (Refereed)
    Abstract [en]

    It has been suggested that technological variations associated with Still Bay assemblages of southern Africa have not been addressed adequately. Here we present a study developed to explore regional and temporal variations in Still Bay point-production strategies. We applied our approach in a regional context to compare the Still Bay point assemblages from Hollow Rock Shelter (Western Cape) and Umhlatuzana Rock Shelter (KwaZulu-Natal). Our interpretation of the point-production strategies implies inter-regional point-production conventions, but also highlights variability and intra-regional knapping strategies used for the production of Still Bay points. These strategies probably reflect flexibility in the organisation of knowledge-transfer systems at work during the later stages of the Middle Stone Age between about 80 ka and 70 ka in South Africa. 

  • 45.
    Idh, Jonna
    et al.
    Linköping University.
    Andersson, Blanka
    Linköping University.
    Lerm, Maria
    Linköping University ; Karolinska Institutet.
    Raffetseder, Johanna
    Linköping University.
    Eklund, Daniel
    Linköping University.
    Woksepp, Hanna
    Linnaeus University, Faculty of Health and Life Sciences, Department of Medicine and Optometry. Kalmar County Hospital.
    Werngren, Jim
    Public Health Agency Sweden.
    Mansjo, Mikael
    Public Health Agency Sweden.
    Sundqvist, Tommy
    Linköping University.
    Stendahl, Olle
    Linköping University.
    Schön, Thomas
    Linnaeus University, Faculty of Health and Life Sciences, Department of Medicine and Optometry. Linköping University ; Kalmar County Hospital.
    Reduced susceptibility of clinical strains of Mycobacterium tuberculosis to reactive nitrogen species promotes survival in activated macrophages2017In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 7, article id e0181221Article in journal (Refereed)
    Abstract [en]

    Background Drugs such as isoniazid (INH) and pretomanid (PRT), used against Mycobacterium tuberculosis are active partly through generation of reactive nitrogen species (RNS). The aim of this study was to explore variability in intracellular susceptibility to nitric oxide (NO) in clinical strains of M. tuberculosis. Method Luciferase-expressing clinical M. tuberculosis strains with or without INH resistance were exposed to RNS donors (DETA/NO and SIN-1) in broth cultures and bacterial survival was analysed by luminometry. NO-dependent intracellular killing in a selection of strains was assessed in interferon gamma/lipopolysaccharide-activated murine macrophages using the NO inhibitor L-NMMA. Results When M. tuberculosis H37Rv was compared to six clinical isolates and CDC1551, three isolates with inhA mediated INH resistance showed significantly reduced NO-susceptibility in broth culture. All strains showed a variable but dose-dependent susceptibility to RNS donors. Two clinical isolates with increased susceptibility to NO exposure in broth compared to H37Rv were significantly inhibited by activated macrophages whereas there was no effect on growth inhibition when activated macrophages were infected by clinical strains with higher survival to NO exposure in broth. Furthermore, the most NO-tolerant clinical isolate showed increased resistance to PRT both in broth culture and the macrophage model compared to H37Rv in the absence of mutational resistance in genes associated to reduced susceptibility against PRT or NO. Conclusion In a limited number of clinical M. tuberculosis isolates we found a significant difference in susceptibility to NO between clinical isolates, both in broth cultures and in macrophages. Our results indicate that mycobacterial susceptibility to cellular host defence mechanisms such as NO need to be taken into consideration when designing new therapeutic strategies.

  • 46.
    Johansson, Håkan
    et al.
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science.
    Ellström, Patrik
    Uppsala University.
    Artursson, Karin
    National Veterinary Institute.
    Berg, Charlotte
    Swedish University of Agricultural Sciences.
    Bonnedahl, Jonas
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science. Kalmar County Hospital.
    Hansson, Ingrid
    Swedish University of Agricultural Sciences.
    Hernandez, Jorge
    Uppsala University;Kalmar County Hospital.
    Lopez-Martin, Juana
    Univ Concepcion, Chile.
    Medina-Vogel, Gonzalo
    Univ Andres Bello, Chile.
    Moreno, Lucile
    Univ Concepcion, Chile.
    Olsen, Björn
    Uppsala University.
    Engvall, Eva Olsson
    National Veterinary Institute.
    Skarin, Hanna
    National Veterinary Institute.
    Troell, Karin
    National Veterinary Institute.
    Waldenström, Jonas
    Linnaeus University, Faculty of Health and Life Sciences, Department of Biology and Environmental Science.
    Agren, Joakim
    National Veterinary Institute.
    Gonzalez-Acuna, Daniel
    Univ Concepcion, Chile.
    Characterization of Campylobacter spp. isolated from wild birds in the Antarctic and Sub-Antarctic2018In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 11, article id e0206502Article in journal (Refereed)
    Abstract [en]

    A lack of knowledge of naturally occurring pathogens is limiting our ability to use the Antarctic to study the impact human-mediated introduction of infectious microorganisms have on this relatively uncontaminated environment. As no large-scale coordinated effort to remedy this lack of knowledge has taken place, we rely on smaller targeted efforts to both study present microorganisms and monitor the environment for introductions. In one such effort, we isolated Campylobacter species from fecal samples collected from wild birds in the Antarctic Peninsula and the sub-Antarctic island of South Georgia. Indeed, in South Georgia, we found Campylobacter lari and the closely related Campylobacter peloridis, but also distantly related human-associated multilocus sequence types of Campylobacter jejuni. In contrast, in the Antarctic Peninsula, we found C. tart and two closely related species, Campylobacter subantarcticus and Campylobacter volucris, but no signs of human introduction. In fact, our finding of human-associated sequence types of C. jejuni in South Georgia, but not in the Antarctic Peninsula, suggests that efforts to limit the spread of infectious microorganisms to the Antarctic have so far been successful in preventing the introduction of C. jejuni. However, we do not know how it came to South Georgia and whether the same mode of introduction could spread it from there to the Antarctic Peninsula.

  • 47.
    Johansson, Karin S. L.
    et al.
    Swedish University of Agricultural Sciences.
    Vrede, Tobias
    Swedish University of Agricultural Sciences.
    Lebret, Karen
    Lund University.
    Johnson, Richard K.
    Swedish University of Agricultural Sciences.
    Zooplankton Feeding on the Nuisance Flagellate Gonyostomum semen2013In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 5, p. e62557-Article in journal (Refereed)
    Abstract [en]

    The large bloom-forming flagellate Gonyostomum semen has been hypothesized to be inedible to naturally occurring zooplankton due to its large cell size and ejection of long slimy threads (trichocysts) induced by physical stimulation. In a grazing experiment using radiolabelled algae and zooplankton collected from lakes with recurring blooms of G. semen and lakes that rarely experience blooms, we found that Eudiaptomus gracilis and Holopedium gibberum fed on G. semen at high rates, whereas Daphnia cristata and Ceriodaphnia spp. did not. Grazing rates of E. gracilis were similar between bloom-lakes and lakes with low biomass of G. semen, indicating that the ability to feed on G. semen was not a result of local adaptation. The high grazing rates of two of the taxa in our experiment imply that some of the nutrients and energy taken up by G. semen can be transferred directly to higher trophic levels, although the predominance of small cladocerans during blooms may limit the importance of G. semen as a food resource. Based on grazing rates and previous observations on abundances of E. gracilis and H. gibberum, we conclude that there is a potential for grazer control of G. semen and discuss why blooms of G. semen still occur.

  • 48.
    Johansson, Ulrika
    et al.
    Swedish University of Agricultural Sciences ; Karolinska Institutet.
    Ria, Massimiliano
    Karolinska Institutet.
    Åvall, Karin
    Karolinska Institutet.
    Shalaly, Nancy Dekki
    KTH Royal Institute of Technology.
    Zaisev, Sergei V.
    Karolinska Institutet.
    Berggren, Per-Olof
    Karolinska Institutet.
    Hedhammar, My
    Karolinska Institutet.
    Pancreatic Islet Survival and Engraftment Is Promoted by Culture on Functionalized Spider Silk Matrices2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 19, no 10, p. 1-21Article in journal (Refereed)
    Abstract [en]

    Transplantation of pancreatic islets is one approach for treatment of diabetes, however, hampered by the low availability of viable islets. Islet isolation leads to disruption of the environment surrounding the endocrine cells, which contributes to eventual cell death. The reestablishment of this environment is vital, why we herein investigated the possibility of using recombinant spider silk to support islets in vitro after isolation. The spider silk protein 4RepCT was formulated into three different formats; 2D-film, fiber mesh and 3D-foam, in order to provide a matrix that can give the islets physical support in vitro. Moreover, cell-binding motifs from laminin were incorporated into the silk protein in order to create matrices that mimic the natural cell environment. Pancreatic mouse islets were thoroughly analyzed for adherence, necrosis and function after in vitro maintenance on the silk matrices. To investigate their suitability for transplantation, we utilized an eye model which allows in vivo imaging of engraftment. Interestingly, islets that had been maintained on silk foam during in vitro culture showed improved revascularization. This coincided with the observation of preserved islet architecture with endothelial cells present after in vitro culture on silk foam. Selected matrices were further evaluated for long-term preservation of human islets. Matrices with the cell-binding motif RGD improved human islet maintenance (from 36% to 79%) with preserved islets architecture and function for over 3 months in vitro. The islets established cell-matrix contacts and formed vessel-like structures along the silk. Moreover, RGD matrices promoted formation of new, insulin-positive islet-like clusters that were connected to the original islets via endothelial cells. On silk matrices with islets from younger donors (<35 year), the amount of newly formed islet-like clusters found after 1 month in culture were almost double compared to the initial number of islets added.

  • 49.
    Jonason, Dennis
    et al.
    Linköping University ; Swedish University of Agricultural Sciences (SLU).
    Franzén, Markus
    UFZ Helmholtz Centre for Environmental Research, Germany.
    Ranius, Thomas
    Swedish University of Agricultural Sciences (SLU).
    Surveying moths using light traps: effects of weather and time of year2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 3, article id e92453Article in journal (Refereed)
    Abstract [en]

    Light trapping is an ideal method for surveying nocturnal moths, but in the absence of standardised survey methods effects of confounding factors may impede interpretation of the acquired data. We explored the influence of weather, time of year, and light source on nightly catches of macro moths in light traps, and compared four strategies for sampling by estimating observed species richness using rarefaction. We operated two traps with different light sources for 225 consecutive nights from mid-March to the end of October in eastern Germany in 2011. In total, 49 472 individuals of 372 species were recorded. Species richness and abundance per night were mainly influenced by night temperature, humidity and lamp type. With a limited sample size (<10 nights) it was slightly better to concentrate sampling on the warmest summer nights, but with more sampling nights it was slightly better to sample during the warmest nights in each month (March to October). By exploiting the higher moth activity during warm nights and an understanding of the species' phenology, it is possible to increase the number of species caught and reduce effects of confounding abiotic factors.

  • 50.
    Jourdain, Elsa
    et al.
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences. INRA, France.
    Gunnarsson, Gunnar
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences. Kristianstad University.
    Wahlgren, John
    Karolinska Institutet ; Swedish Institute for Infectious Disease Control.
    Latorre-Margalef, Neus
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Bröjer, Caroline
    National Veterinary Institute ; University of Agricultural Sciences.
    Sahlin, Sofie
    Karolinska Institutet ; Swedish Institute for Infectious Disease Control.
    Svensson, Lovisa
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Waldenström, Jonas
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences.
    Lundkvist, Åke
    Swedish Institute for Infectious Disease Control.
    Olsen, Björn
    Linnaeus University, Faculty of Science and Engineering, School of Natural Sciences. Uppsala University.
    Influenza Virus in a Natural Host, the Mallard: Experimental Infection Data2010In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 5, no 1, article id e8935Article in journal (Refereed)
    Abstract [en]

    Wild waterfowl, particularly dabbling ducks such as mallards (Anas platyrhynchos), are considered the main reservoir of low-pathogenic avian influenza viruses (LPAIVs). They carry viruses that may evolve and become highly pathogenic for poultry or zoonotic. Understanding the ecology of LPAIVs in these natural hosts is therefore essential. We assessed the clinical response, viral shedding and antibody production of juvenile mallards after intra-esophageal inoculation of two LPAIV subtypes previously isolated from wild congeners. Six ducks, equipped with data loggers that continually monitored body temperature, heart rate and activity, were successively inoculated with an H7N7 LPAI isolate (day 0), the same H7N7 isolate again (day 21) and an H5N2 LPAI isolate (day 35). After the first H7N7 inoculation, the ducks remained alert with no modification of heart rate or activity. However, body temperature transiently increased in four individuals, suggesting that LPAIV strains may have minor clinical effects on their natural hosts. The excretion patterns observed after both reinoculations differed strongly from those observed after the primary H7N7 inoculation, suggesting that not only homosubtypic but also heterosubtypic immunity exist. Our study suggests that LPAI infection has minor clinically measurable effects on mallards and that mallard ducks are able to mount immunological responses protective against heterologous infections. Because the transmission dynamics of LPAIVs in wild populations is greatly influenced by individual susceptibility and herd immunity, these findings are of high importance. Our study also shows the relevance of using telemetry to monitor disease in animals.

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