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  • 1.
    Abdelfattah, Ahmed
    et al.
    Stockholm University, Faculty of Science, Department of Ecology, Environment and Plant Sciences. Università Mediterranea di Reggio Calabria, Italy.
    Ruano-Rosa, David
    Cacciola, Santa Olga
    Nicosia, Maria G. Li Destri
    Schena, Leonardo
    Impact of Bactrocera oleae on the fungal microbiota of ripe olive drupes2018In: PLOS ONE, E-ISSN 1932-6203, Vol. 13, no 11, article id e0199403Article in journal (Refereed)
    Abstract [en]

    The olive fruit fly (OFF), Bactrocera oleae is the most devastating pest affecting olive fruit worldwide. Previous investigations have addressed the fungal microbiome associated with olive drupes or B. oleae, but the impact of the insect on fungal communities of olive fruit remains undescribed. In the present work, the fungal microbiome of olive drupes, infested and non-infested by the OFF, was investigated in four different localities and cultivars. Olive fruit fly infestations caused a general reduction of the fungal diversity, a higher quantity of the total DNA and an increase in taxa that remained unidentified or had unknown roles. The infestations led to imbalanced fungal communities with the growth of taxa that are usually outcompeted. While it was difficult to establish a cause-effect link between fly infestation and specific fungi, it is clear that the fly alters the natural microbial balance, especially the low abundant taxa. On the other hand, the most abundant ones, were not significantly influenced by the insect. In fact, despite the slight variation between the sampling locations, Aureobasidium, Cladosporium, and Alternaria, were the dominant genera, suggesting the existence of a typical olive fungal microbiome.

  • 2.
    Acerbi, Alberto
    et al.
    Stockholm University, Faculty of Humanities, Centre for Cultural Evolution.
    Ghirlanda, Stefano
    Stockholm University, Faculty of Humanities, Centre for Cultural Evolution.
    Enquist, Magnus
    Stockholm University, Faculty of Humanities, Centre for Cultural Evolution. Stockholm University, Faculty of Science, Department of Zoology.
    The logic of fashion cycles2012In: PLOS ONE, E-ISSN 1932-6203, Vol. 7, no 3, p. e32541-Article in journal (Refereed)
    Abstract [en]

    Many cultural traits exhibit volatile dynamics, commonly dubbed fashions or fads. Here we show that realistic fashion-like dynamics emerge spontaneously if individuals can copy others' preferences for cultural traits as well as traits themselves. We demonstrate this dynamics in simple mathematical models of the diffusion, and subsequent abandonment, of a single cultural trait which individuals may or may not prefer. We then simulate the coevolution between many cultural traits and the associated preferences, reproducing power-law frequency distributions of cultural traits (most traits are adopted by few individuals for a short time, and very few by many for a long time), as well as correlations between the rate of increase and the rate of decrease of traits (traits that increase rapidly in popularity are also abandoned quickly and vice versa). We also establish that alternative theories, that fashions result from individuals signaling their social status, or from individuals randomly copying each other, do not satisfactorily reproduce these empirical observations.

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  • 3.
    Acerbi, Alberto
    et al.
    Stockholm University, Faculty of Humanities, Centre for the Study of Cultural Evolution. University of Bristol, United Kingdom.
    Lampos, Vasileios
    Garnett, Philip
    Bentley, R. Alexander
    The Expression of Emotions in 20th Century Books2013In: PLOS ONE, E-ISSN 1932-6203, Vol. 8, no 3, article id e59030Article in journal (Refereed)
    Abstract [en]

    We report here trends in the usage of mood words, that is, words carrying emotional content, in 20th century English language books, using the data set provided by Google that includes word frequencies in roughly 4% of all books published up to the year 2008. We find evidence for distinct historical periods of positive and negative moods, underlain by a general decrease in the use of emotion-related words through time. Finally, we show that, in books, American English has become decidedly more emotional than British English in the last half-century, as a part of a more general increase of the stylistic divergence between the two variants of English language.

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  • 4. Affatati, Alice
    et al.
    Scaini, Chiara
    Scaini, Anna
    Stockholm University, Faculty of Science, Department of Physical Geography. Stockholm University, Faculty of Science, The Bolin Centre for Climate Research (together with KTH & SMHI).
    The role of operators in sustainable whale-watching tourism: Proposing a continuous training framework2024In: PLOS ONE, E-ISSN 1932-6203, Vol. 19, no 1, article id e0296241Article in journal (Refereed)
    Abstract [en]

    Whale watching is considered a form of green tourism, but can affect marine ecosystems, impacting cetaceans’ behavior and potentially increasing acoustic pollution. A more sustainable whale-watching practice should employ a comprehensive approach involving all stakeholders, but whale-watching operators are rarely involved. We propose a method to assess whale–watching operators’ perceptions regarding the possible effects of their activity on marine fauna and preferred mitigation solutions, by means of online questionnaires and website communication strategies. Results from Canadian whale-watching operators show that they observe regulations regarding distance to whales but only partially perceive general vessels’ impacts on fauna. Three recognized whale-watching experts identify the need for continuous training targeted at operators, which should include the impacts on marine ecosystems. A continuous training framework is proposed that targets whale-watching operators in addition to tourists, and involves scientists in several steps of the approach. This study serves as a starting point to involve operators’ in order to advance towards a sustainable whale-watching tourism.

  • 5. Aho, Vilma
    et al.
    Ollila, Hanna M.
    Rantanen, Ville
    Kronholm, Erkki
    Surakka, Ida
    van Leeuwen, Wessel M. A.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. University of Helsinki, Finland; Finnish Institute of Occupational Health, Finland.
    Lehto, Maili
    Matikainen, Sampsa
    Ripatti, Samuli
    Härmä, Mikko
    Sallinen, Mikael
    Salomaa, Veikko
    Jauhiainen, Matti
    Alenius, Harri
    Paunio, Tiina
    Porkka-Heiskanen, Tarja
    Partial Sleep Restriction Activates Immune Response-Related Gene Expression Pathways: Experimental and Epidemiological Studies in Humans2013In: PLOS ONE, E-ISSN 1932-6203, Vol. 8, no 10, article id e77184Article in journal (Refereed)
    Abstract [en]

    Epidemiological studies have shown that short or insufficient sleep is associated with increased risk for metabolic diseases and mortality. To elucidate mechanisms behind this connection, we aimed to identify genes and pathways affected by experimentally induced, partial sleep restriction and to verify their connection to insufficient sleep at population level. The experimental design simulated sleep restriction during a working week: sleep of healthy men (N = 9) was restricted to 4 h/night for five nights. The control subjects (N = 4) spent 8 h/night in bed. Leukocyte RNA expression was analyzed at baseline, after sleep restriction, and after recovery using whole genome microarrays complemented with pathway and transcription factor analysis. Expression levels of the ten most up-regulated and ten most down-regulated transcripts were correlated with subjective assessment of insufficient sleep in a population cohort (N = 472). Experimental sleep restriction altered the expression of 117 genes. Eight of the 25 most up-regulated transcripts were related to immune function. Accordingly, fifteen of the 25 most up-regulated Gene Ontology pathways were also related to immune function, including those for B cell activation, interleukin 8 production, and NF-kappa B signaling (P<0.005). Of the ten most up-regulated genes, expression of STX16 correlated negatively with self-reported insufficient sleep in a population sample, while three other genes showed tendency for positive correlation. Of the ten most down-regulated genes, TBX21 and LGR6 correlated negatively and TGFBR3 positively with insufficient sleep. Partial sleep restriction affects the regulation of signaling pathways related to the immune system. Some of these changes appear to be long-lasting and may at least partly explain how prolonged sleep restriction can contribute to inflammation-associated pathological states, such as cardiometabolic diseases.

  • 6. Al-Adhami, Maissa
    et al.
    Berglund, Erik
    Wångdahl, Josefin
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Uppsala University, Sweden.
    Salari, Raziye
    A cross-sectional study of health and well-being among newly settled refugee migrants in Sweden–The role of health literacy, social support and self-efficacy2022In: PLOS ONE, E-ISSN 1932-6203, Vol. 17, no 12, article id e0279397Article in journal (Refereed)
    Abstract [en]

    Structural barriers such as inadequate housing, lack of employment opportunities, and discrimination are known to adversely affect the health of newly settled refugee migrants. However, these barriers remain largely unresolved and unaddressed. Thus, there is a need to better understand how other factors, such as individual-level health resources, may influence health and mitigate ill health in the early post-migration phase. In this study, we aimed to explore the relationship between health outcomes and individual health resources including health literacy, social support, and self-efficacy in newly settled refugee migrants. Survey data was collected from 787 refugee migrants in Sweden. Logistical regression analysis showed that limited health literacy, lack of emotional support, and low self-efficacy were consistently associated with poor health outcomes. Demographic variables such as gender, education, and type of residence permit were not as imperative. Individual-level health resources may play an important role in the general and psychological well-being of newly settled migrants. Promoting health literacy and facilitating the attainment of social support may buffer for structural challenges in the establishment phase and enhance the prospects of later health and social integration.

  • 7.
    Alemán Bañón, José
    et al.
    Stockholm University, Faculty of Humanities, Department of Swedish Language and Multilingualism, Centre for Research on Bilingualism.
    Fiorentino, Robert
    Gabriele, Alison
    Using event-related potentials to track morphosyntactic development in second language learners: The processing of number and gender agreement in Spanish2018In: PLOS ONE, E-ISSN 1932-6203, Vol. 13, no 7, article id e0200791Article in journal (Refereed)
    Abstract [en]

    We used event-related potentials to investigate morphosyntactic development in 78 adult English-speaking learners of Spanish as a second language (L2) across the proficiency spectrum. We examined how development is modulated by the similarity between the native language (L1) and the L2, by comparing number (a feature present in English) and gender agreement (novel feature). We also investigated how development is impacted by structural distance, manipulating the distance between the agreeing elements by probing both within-phrase (fruta muy jugosafruit(-FEM-SG) very juicy(-FEM-SG)) and across-phrase agreement (fresa es acida strawberry(-FEM-SG) is tart(-FEM-SG)). Regression analyses revealed that the learners' overall proficiency, as measured by a standardized test, predicted their accuracy with the target properties in the grammaticality judgment task (GJT), but did not predict P600 magnitude to the violations. However, a relationship emerged between immersion in Spanish-speaking countries and P600 magnitude for gender. Our results also revealed a correlation between accuracy in the GJT and P600 magnitude, suggesting that behavioral sensitivity to the target property predicts neurophysiological sensitivity. Subsequent group analyses revealed that the highest-proficiency learners showed equally robust P600 effects for number and gender. This group also elicited more positive waveforms for within- than across-phrase agreement overall, similar to the native controls. The lowest-proficiency learners showed a P600 for number overall, but no effects for gender. Unlike the highest-proficiency learners, they also showed no sensitivity to structural distance, suggesting that sensitivity to such linguistic factors develops over time. Overall, these results suggest an important role for proficiency in morphosyntactic development, although differences emerged between behavioral and electrophysiological measures. While L2 proficiency predicted behavioral sensitivity to agreement, development with respect to the neurocognitive mechanisms recruited in processing only emerged when comparing the two extremes of the proficiency spectrum. Importantly, while both L1-L2 similarity and hierarchical structure impact development, they do not constrain it.

  • 8.
    Alonso Aller, Elisa
    et al.
    Stockholm University, Faculty of Science, Department of Ecology, Environment and Plant Sciences.
    Jiddawi, Narriman S.
    Eklöf, Johan S.
    Stockholm University, Faculty of Science, Department of Ecology, Environment and Plant Sciences.
    Marine protected areas increase temporal stability of community structure, but not density or diversity, of tropical seagrass fish communities2017In: PLOS ONE, E-ISSN 1932-6203, Vol. 12, no 8, article id e0183999Article in journal (Refereed)
    Abstract [en]

    Marine protected areas (MPAs) have been shown to increase long-term temporal stability of fish communities and enhance ecosystem resilience to anthropogenic disturbance. Yet, the potential ability of MPAs to buffer effects of environmental variability at shorter time scales remains widely unknown. In the tropics, the yearly monsoon cycle is a major natural force affecting marine organisms in tropical regions, and its timing and severity are predicted to change over the coming century, with potentially severe effects on marine organisms, ecosystems and ecosystem services. Here, we assessed the ability of MPAs to buffer effects of monsoon seasonality on seagrass-associated fish communities, using a field survey in two MPAs (no-take zones) and two unprotected (open-access) sites around Zanzibar (Tanzania). We assessed the temporal stability of fish density and community structure within and outside MPAs during three monsoon seasons in 2014-2015, and investigated several possible mechanisms that could regulate temporal stability. Our results show that MPAs did not affect fish density and diversity, but that juvenile fish densities were temporally more stable within MPAs. Second, fish community structure was more stable within MPAs for juvenile and adult fish, but not for subadult fish or the total fish community. Third, the observed effects may be due to a combination of direct and indirect (seagrass-mediated) effects of seasonality and, potentially, fluctuating fishing pressure outside MPAs. In summary, these MPAs may not have the ability to enhance fish density and diversity and to buffer effects of monsoon seasonality on the whole fish community. However, they may increase the temporal stability of certain groups, such as juvenile fish. Consequently, our results question whether MPAs play a general role in the maintenance of biodiversity and ecosystem functioning under changing environmental conditions in tropical seagrass fish communities.

  • 9.
    Altmejd, Adam
    et al.
    Stockholm University, Faculty of Social Sciences, The Swedish Institute for Social Research (SOFI). Stockholm School of Economics, Sweden.
    Dreber, Anna
    Forsell, Eskil
    Huber, Juergen
    Imai, Taisuke
    Johannesson,, Magnus
    Kirchler, Michael
    Nave, Gideon
    Camerer, Colin
    Predicting the replicability of social science lab experiments2019In: PLOS ONE, E-ISSN 1932-6203, Vol. 14, no 12, article id e0225826Article in journal (Refereed)
    Abstract [en]

    We measure how accurately replication of experimental results can be predicted by black-box statistical models. With data from four large-scale replication projects in experimental psychology and economics, and techniques from machine learning, we train predictive models and study which variables drive predictable replication. The models predicts binary replication with a cross-validated accuracy rate of 70% (AUC of 0.77) and estimates of relative effect sizes with a Spearman ρ of 0.38. The accuracy level is similar to market-aggregated beliefs of peer scientists [1, 2]. The predictive power is validated in a pre-registered out of sample test of the outcome of [3], where 71% (AUC of 0.73) of replications are predicted correctly and effect size correlations amount to ρ = 0.25. Basic features such as the sample and effect sizes in original papers, and whether reported effects are single-variable main effects or two-variable interactions, are predictive of successful replication. The models presented in this paper are simple tools to produce cheap, prognostic replicability metrics. These models could be useful in institutionalizing the process of evaluation of new findings and guiding resources to those direct replications that are likely to be most informative.

  • 10.
    Andersson, Erik
    et al.
    Stockholm University, Faculty of Science, Stockholm Resilience Centre.
    Lindborg, Regina
    Stockholm University, Faculty of Science, Department of Physical Geography and Quaternary Geology.
    Species Richness and Assemblages in Landscapes of Different Farming Intensity - Time to Revise Conservation Strategies?2014In: PLOS ONE, E-ISSN 1932-6203, Vol. 9, no 10, p. e109816-Article in journal (Refereed)
    Abstract [en]

    Worldwide conservation goals to protect biodiversity emphasize the need to rethink which objectives are most suitable for different landscapes. Comparing two different Swedish farming landscapes, we used survey data on birds and vascular plants to test whether landscapes with large, intensively managed farms had lower richness and diversity of the two taxa than landscapes with less intensively managed small farms, and if they differed in species composition. Landscapes with large intensively managed farms did not have lower richness than smaller low intensively managed farms. The landscape types were also similar in that they had few red listed species, normally targeted in conservation. Differences in species composition demonstrate that by having both types of agricultural landscapes regional diversity is increased, which is seldom captured in the objectives for agro-environmental policies. Thus we argue that focus on species richness or red listed species would miss the actual diversity found in the two landscape types. Biodiversity conservation, especially in production landscapes, would therefore benefit from a hierarchy of local to regional objectives with explicit targets in terms of which aspects of biodiversity to focus on.

  • 11. Andersson, Evelyn
    et al.
    Rück, Christian
    Lavebratt, Catharina
    Hedman, Erik
    Schalling, Martin
    Lindefors, Nils
    Eriksson, Elias
    Carlbring, Per
    Stockholm University, Faculty of Social Sciences, Department of Psychology.
    Andersson, Gerhard
    Furmark, Tomas
    Genetic Polymorphisms in Monoamine Systems and Outcome of Cognitive Behavior Therapy for Social Anxiety Disorder2013In: PLOS ONE, E-ISSN 1932-6203, Vol. 8, no 11, article id e79015Article in journal (Refereed)
    Abstract [en]

    Objective

    The role of genetics for predicting the response to cognitive behavior therapy (CBT) for social anxiety disorder (SAD) has only been studied in one previous investigation. The serotonin transporter (5-HTTLPR), the catechol-o-methyltransferase (COMT) val158met, and the tryptophan hydroxylase-2 (TPH2) G-703Tpolymorphisms are implicated in the regulation of amygdala reactivity and fear extinction and therefore might be of relevance for CBT outcome. The aim of the present study was to investigate if these three gene variants predicted response to CBT in a large sample of SAD patients.

    Method

    Participants were recruited from two separate randomized controlled CBT trials (trial 1: n = 112, trial 2: n = 202). Genotyping were performed on DNA extracted from blood or saliva samples. Effects were analyzed at follow-up (6 or 12 months after treatment) for both groups and for each group separately at post-treatment. The main outcome measure was the Liebowitz Social Anxiety Scale Self-Report.

    Results

    At long-term follow-up, there was no effect of any genotype, or gene × gene interactions, on treatment response. In the subsamples, there was time by genotype interaction effects indicating an influence of the TPH2 G-703T-polymorphism on CBT short-term response, however the direction of the effect was not consistent across trials.

    Conclusions

    None of the three gene variants, 5-HTTLPR, COMTval158met and TPH2 G-703T, was associated with long-term response to CBT for SAD.

  • 12.
    Andreasson, Anna
    et al.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Karshikoff, Bianka
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Lidberg, Lisa
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Åkerstedt, Torbjörn
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Ingvar, Martin
    Hoglund, Caroline Olgart
    Axelsson, John
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    The effect of a transient immune activation on subjective health perception in two placebo controlled randomised experiments2019In: PLOS ONE, E-ISSN 1932-6203, Vol. 14, no 3, article id e0212313Article in journal (Refereed)
    Abstract [en]

    Background Patient-reported outcomes predict mortality and play increasingly important roles in care, but factors that modify central measures such as health ratings have been little investigated. Building on designated immune-to-brain pathways, we aimed to determine how a short-term induced inflammation response impacts self-reported health status. Methods Lipopolysaccharide injections were used to provoke acute systemic inflammatory responses in healthy men and women and were compared to placebo in two double-blind randomized experiments. In Experiment 1, 8 individuals (mean 24 years; SD = 3.7) received lipopolysaccharide 0.8 ng/kg once and placebo once in a cross-over design, and in Experiment 2, 52 individuals received either lipopolysaccharide 0.6 ng/kg or placebo once (28.6 years; SD = 7.1). Main outcomes were perceived health (general and current), sickness behaviour (like fatigue, pain and negative affect), and plasma interleukin-6, interleukin-8 and tumour necrosis factor-alpha, before and after injection. Results Compared to placebo, lipopolysaccharide lead to a deterioration in both self-rated general (Experiment 1, b = 1.88 for 0.8 ng/kg) and current health (Experiment 1 b = -3.00; and Experiment 2 b = -1.79) 1.5h after injection (p's<0.01), effects that remained after 4.5 to 5 hours (p's<0.05). The effect on current health in Experiment 2 was mediated by increased inflammation and sickness behaviour in response to lipopolysaccharide injection (beta = -0.28, p = 0.01). Conclusion Health is drastically re-evaluated during inflammatory activation. The findings are consistent with notions that inflammation forms part of health-relevant interoceptive computations of bodily state, and hint at one mechanism as to why subjective health predicts longevity.

  • 13.
    Andreasson, Claes
    et al.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Schick, Anna J.
    Pfeiffer, Susanne M.
    Sarov, Mihail
    Stewart, Francis
    Wurst, Wolfgang
    Schick, Joel A.
    Direct Cloning of Isogenic Murine DNA in Yeast and Relevance of Isogenicity for Targeting in Embryonic Stem Cells2013In: PLOS ONE, E-ISSN 1932-6203, Vol. 8, no 9, p. e74207-Article in journal (Refereed)
    Abstract [en]

    Efficient gene targeting in embryonic stem cells requires that modifying DNA sequences are identical to those in the targeted chromosomal locus. Yet, there is a paucity of isogenic genomic clones for human cell lines and PCR amplification cannot be used in many mutation-sensitive applications. Here, we describe a novel method for the direct cloning of genomic DNA into a targeting vector, pRTVIR, using oligonucleotide-directed homologous recombination in yeast. We demonstrate the applicability of the method by constructing functional targeting vectors for mammalian genes Uhrf1 and Gfap. Whereas the isogenic targeting of the gene Uhrf1 showed a substantial increase in targeting efficiency compared to non-isogenic DNA in mouse E14 cells, E14-derived DNA performed better than the isogenic DNA in JM8 cells for both Uhrf1 and Gfap. Analysis of 70 C57BL/6-derived targeting vectors electroporated in JM8 and E14 cell lines in parallel showed a clear dependence on isogenicity for targeting, but for three genes isogenic DNA was found to be inhibitory. In summary, this study provides a straightforward methodological approach for the direct generation of isogenic gene targeting vectors.

  • 14.
    Angeler, David G.
    et al.
    Stockholm University, Faculty of Science, Department of Ecology, Environment and Plant Sciences. Swedish University of Agricultural Sciences, Sweden.
    Allen, Craig R.
    Garmestani, Ahjond S.
    Gunderson, Lance H.
    Hjerne, Olle
    Stockholm University, Faculty of Science, Department of Ecology, Environment and Plant Sciences.
    Winder, Monika
    Stockholm University, Faculty of Science, Department of Ecology, Environment and Plant Sciences.
    Quantifying the Adaptive Cycle2015In: PLOS ONE, E-ISSN 1932-6203, Vol. 10, no 12, article id e0146053Article in journal (Refereed)
    Abstract [en]

    The adaptive cycle was proposed as a conceptual model to portray patterns of change in complex systems. Despite the model having potential for elucidating change across systems, it has been used mainly as a metaphor, describing system dynamics qualitatively. We use a quantitative approach for testing premises (reorganisation, conservatism, adaptation) in the adaptive cycle, using Baltic Sea phytoplankton communities as an example of such complex system dynamics. Phytoplankton organizes in recurring spring and summer blooms, a well-established paradigm in planktology and succession theory, with characteristic temporal trajectories during blooms that may be consistent with adaptive cycle phases. We used long-term (1994-2011) data and multivariate analysis of community structure to assess key components of the adaptive cycle. Specifically, we tested predictions about: reorganisation: spring and summer blooms comprise distinct community states; conservatism: community trajectories during individual adaptive cycles are conservative; and adaptation: phytoplankton species during blooms change in the long term. All predictions were supported by our analyses. Results suggest that traditional ecological paradigms such as phytoplankton successional models have potential for moving the adaptive cycle from a metaphor to a framework that can improve our understanding how complex systems organize and reorganize following collapse. Quantifying reorganization, conservatism and adaptation provides opportunities to cope with the intricacies and uncertainties associated with fast ecological change, driven by shifting system controls. Ultimately, combining traditional ecological paradigms with heuristics of complex system dynamics using quantitative approaches may help refine ecological theory and improve our understanding of the resilience of ecosystems.

  • 15.
    Angleman, Sara B.
    et al.
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Santoni, Giola
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Pilotto, Alberto
    Fratiglioni, Laura
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI). Stockholm Gerontology Research Center, Karolinska Institutet.
    Welmer, Anna-Karin
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Multidimensional Prognostic Index in Association with Future Mortality and Number of Hospital Days in a Population-Based Sample of Older Adults: Results of the EU Funded MPI_AGE Project2015In: PLOS ONE, E-ISSN 1932-6203, Vol. 10, no 7, article id e0133789Article in journal (Refereed)
    Abstract [en]

    Background The Multidimensional Prognostic Index (MPI) has been found to predict mortality in patients with a variety of clinical conditions. We aimed to assess the association of the MPI with future mortality and number of in-hospital days for the first time in a population-based cohort. Methods The study population consisted of 2472 persons, aged 66-99 years, from the Swedish National Study on Aging and Care in Kungsholmen, Sweden, who underwent the baseline visit 2001-4, and were followed up >10 years for in-hospital days and >12 years for mortality. The MPI was a modified version of the original and aggregated seven domains (personal and instrumental activities of daily living, cognitive function, illness severity and comorbidity, number of medications, co-habitation status, and nutritional status). The MPI score was divided into risk groups: low, medium and high. Number of in-hospital days (within 1, 3 and 10 years) and mortality data were derived from official registries. All analyses were age-stratified (sexagenarians, septuagenarians, octogenarians, nonagenarians). Results During the follow-up 1331 persons (53.8%) died. Laplace regression models, suggested that median survival in medium risk groups varied by age from 2.2-3.6 years earlier than for those in the corresponding low risk groups (p = 0.002-p<0.001), and median survival in high risk groups varied by age from 3.8-9.0 years earlier than for corresponding low risk groups (p<0.001). For nonagenarians, the median age at death was 3.8 years earlier in the high risk group than for the low risk group (p<0.001). The mean number of in-hospital days increased significantly with higher MPI risk score within 1 and 3 years for people of each age group. Conclusion For the first time, the effectiveness of MPI has been verified in a population-based cohort. Higher MPI risk scores associated with more days in hospital and with fewer years of survival, across a broad and stratified age range.

  • 16. Anh, Nhi
    et al.
    Taylan, Fulya
    Zachariadis, Vasilios
    Ivanov Öfverholm, Ingegerd
    Lindstrand, Anna
    Vezzi, Francesco
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Lötstedt, Britta
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Nordenskjöld, Magnus
    Nordgren, Ann
    Nilsson, Daniel
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab). Karolinska Institutet, Sweden.
    Barbany, Gisela
    High-resolution detection of chromosomal rearrangements in leukemias through mate pair whole genome sequencing2018In: PLOS ONE, E-ISSN 1932-6203, Vol. 13, no 3, article id e0193928Article in journal (Refereed)
    Abstract [en]

    The detection of recurrent somatic chromosomal rearrangements is standard of care for most leukemia types. Even though karyotype analysis-a low-resolution genome-wide chromosome analysis-is still the gold standard, it often needs to be complemented with other methods to increase resolution. To evaluate the feasibility and applicability of mate pair whole genome sequencing (MP-WGS) to detect structural chromosomal rearrangements in the diagnostic setting, we sequenced ten bone marrow samples from leukemia patients with recurrent rearrangements. Samples were selected based on cytogenetic and FISH results at leukemia diagnosis to include common rearrangements of prognostic relevance. Using MP-WGS and in-house bioinformatic analysis all sought rearrangements were successfully detected. In addition, unexpected complexity or additional, previously undetected rearrangements was unraveled in three samples. Finally, the MP-WGS analysis pinpointed the location of chromosome junctions at high resolution and we were able to identify the exact exons involved in the resulting fusion genes in all samples and the specific junction at the nucleotide level in half of the samples. The results show that our approach combines the screening character from karyotype analysis with the specificity and resolution of cytogenetic and molecular methods. As a result of the straightforward analysis and high-resolution detection of clinically relevant rearrangements, we conclude that MP-WGS is a feasible method for routine leukemia diagnostics of structural chromosomal rearrangements.

  • 17. Anstey, Kaarin J.
    et al.
    Cherbuin, Nicolas
    Herath, Pushpani M.
    Qiu, Chengxuan
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Kuller, Lewis H.
    Lopez, Oscar L.
    Wilson, Robert S.
    Fratiglioni, Laura
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    A Self-Report Risk Index to Predict Occurrence of Dementia in Three Independent Cohorts of Older Adults: The ANU-ADRI2014In: PLOS ONE, E-ISSN 1932-6203, Vol. 9, no 1, p. e86141-Article in journal (Refereed)
    Abstract [en]

    Background and Aims: The Australian National University AD Risk Index (ANU-ADRI, http://anuadri.anu.edu.au) is a self-report risk index developed using an evidence-based medicine approach to measure risk of Alzheimer's disease (AD). We aimed to evaluate the extent to which the ANU-ADRI can predict the risk of AD in older adults and to compare the ANU-ADRI to the dementia risk index developed from the Cardiovascular Risk Factors, Aging and Dementia (CAIDE) study for middle-aged cohorts. Methods: This study included three validation cohorts, i.e., the Rush Memory and Aging Study (MAP) (n = 903, age >= 53 years), the Kungsholmen Project (KP) (n = 905, age >= 75 years), and the Cardiovascular Health Cognition Study (CVHS) (n = 2496, age >= 65 years) that were each followed for dementia. Baseline data were collected on exposure to the 15 risk factors included in the ANU-ADRI of which MAP had 10, KP had 8 and CVHS had 9. Risk scores and C-statistics were computed for individual participants for the ANU-ADRI and the CAIDE index. Results: For the ANU-ADRI using available data, the MAP study c-statistic was 0.637 (95% CI 0.596-0.678), for the KP study it was 0.740 (0.712-0.768) and for the CVHS it was 0.733 (0.691-0.776) for predicting AD. When a common set of risk and protective factors were used c-statistics were 0.689 (95% CI 0.650-0.727), 0.666 (0.628-0.704) and 0.734 (0.707-0.761) for MAP, KP and CVHS respectively. Results for CAIDE ranged from c-statistics of 0.488 (0.427-0.554) to 0.595 (0.565-0.625). Conclusion: A composite risk score derived from the ANU-ADRI weights including 8-10 risk or protective factors is a valid, self-report tool to identify those at risk of AD and dementia. The accuracy can be further improved in studies including more risk factors and younger cohorts with long-term follow-up.

  • 18. Anund, Anna
    et al.
    Fors, Carina
    Hallvig, David
    Åkerstedt, Torbjörn
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Kecklund, Göran
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Observer Rated Sleepiness and Real Road Driving: An Explorative Study2013In: PLOS ONE, E-ISSN 1932-6203, Vol. 8, no 5, article id e64782Article in journal (Refereed)
    Abstract [en]

    The aim of the present study was to explore if observer rated sleepiness (ORS) is a feasible method for quantification of driver sleepiness in field studies. Two measures of ORS were used: (1) one for behavioural signs based on facial expression, body gestures and body movements labelled B-ORS, and (2) one based on driving performance e.g. if swerving and other indicators of impaired driving occurs, labelled D-ORS. A limited number of observers sitting in the back of an experimental vehicle on a motorway about 2 hours repeatedly 3 times per day (before lunch, after lunch, at night) observed 24 participant's sleepiness level with help of the two observer scales. At the same time the participant reported subjective sleepiness (KSS), EOG was recorded (for calculation of blink duration) and several driving measure were taken and synchronized with the reporting. Based on mixed model Anova and correlation analysis the result showed that observer ratings of sleepiness based on drivers' impaired performance and behavioural signs are sensitive to extend the general pattern of time awake, circadian phase and time of driving. The detailed analysis of the subjective sleepiness and ORS showed weak correspondence on an individual level. Only 16% of the changes in KSS were predicted by the observer. The correlation between the observer ratings based on performance (D-ORS) and behavioural signs (B-ORS) are high (r = .588), and the B-ORS shows a moderately strong association (r = .360) with blink duration. Both ORS measures show an association (r>0.45) with KSS, whereas the association with driving performance is weak. The results show that the ORS-method detects the expected general variations in sleepy driving in field studies, however, sudden changes in driver sleepiness on a detailed level as 5 minutes is usually not detected; this holds true both when taking into account driving behaviour or driver behavioural signs.

  • 19.
    Arama, Charles
    et al.
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Giusti, Pablo
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Boström, Stephanie
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Varani, Stefania
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Troye Blomberg, Marita
    Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
    Interethnic Differences in Antigen-Presenting Cell Activation and TLR Responses in Malian Children during Plasmodium falciparum Malaria2011In: PLOS ONE, E-ISSN 1932-6203, Vol. 6, no 3, p. e18319-Article in journal (Refereed)
    Abstract [en]

    The Fulani ethnic group from West Africa is relatively better protected against Plasmodium falciparum malaria as compared to other sympatric ethnic groups, such as the Dogon. However, the mechanisms behind this lower susceptibility to malaria are largely unknown, particularly those concerning innate immunity. Antigen-presenting cells (APCs), and in particular dendritic cells (DCs) are important components of the innate and adaptive immune systems. Therefore, in this study we investigated whether APCs obtained from Fulani and Dogon children exhibited differences in terms of activation status and toll-like receptor (TLR) responses during malaria infection. Lower frequency and increased activation was observed in circulating plasmacytoid DCs and BDCA-3+ myeloid DCs of infected Fulani as compared to their uninfected counterparts. Conversely, a higher frequency and reduced activation was observed in the same DC subsets obtained from peripheral blood of P. falciparum-infected Dogon children as compared to their uninfected peers. Moreover, infected individuals of both ethnic groups exhibited higher percentages of both classical and inflammatory monocytes that were less activated as compared to their non-infected counterparts. In line with APC impairment during malaria infection, TLR4, TLR7 and TLR9 responses were strongly inhibited by P. falciparum infection in Dogon children, while no such TLR inhibition was observed in the Fulani children. Strikingly, the TLR-induced IFN-γ release was completely abolished in the Dogon undergoing infection while no difference was seen within infected and non-infected Fulani. Thus, P. falciparum infection is associated with altered activation status of important APC subsets and strongly inhibited TLR responses in peripheral blood of Dogon children. In contrast, P. falciparum induces DC activation and does not affect the innate response to specific TLR ligands in Fulani children. These findings suggest that DCs and TLR signalling may be of importance for the protective immunity against malaria observed in the Fulani.

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  • 20. Ardehed, Angelica
    et al.
    Johansson, Daniel
    Sundqvist, Lisa
    Schagerström, Ellen
    Stockholm University, Faculty of Science, Department of Ecology, Environment and Plant Sciences.
    Zagrodzka, Zuzanna
    Kovaltchouk, Nikolaj A.
    Bergström, Lena
    Kautsky, Lena
    Stockholm University, Faculty of Science, Department of Ecology, Environment and Plant Sciences.
    Rafajlovic, Marina
    Pereyra, Ricardo T.
    Johannesson, Kerstin
    Divergence within and among Seaweed Siblings (Fucus vesiculosus and F. radicans) in the Baltic Sea2016In: PLOS ONE, E-ISSN 1932-6203, Vol. 11, no 8, article id e0161266Article in journal (Refereed)
    Abstract [en]

    Closely related taxa provide significant case studies for understanding evolution of new species but may simultaneously challenge species identification and definition. In the Baltic Sea, two dominant and perennial brown algae share a very recent ancestry. Fucus vesiculosus invaded this recently formed postglacial sea 8000 years ago and shortly thereafter Fucus radicans diverged from this lineage as an endemic species. In the Baltic Sea both species reproduce sexually but also recruit fully fertile new individuals by asexual fragmentation. Earlier studies have shown local differences in morphology and genetics between the two taxa in the northern and western Bothnian Sea, and around the island of Saaremaa in Estonia, but geographic patterns seemin conflict with a single origin of F. radicans. To investigate the relationship between northern and Estonian distributions, we analysed the genetic variation using 9 microsatellite loci in populations from eastern Bothnian Sea, Archipelago Sea and the Gulf of Finland. These populations are located in between earlier studied populations. However, instead of bridging the disparate genetic gap between N-W Bothnian Sea and Estonia, as expected from a simple isolation-by-distance model, the new populations substantially increased overall genetic diversity and showed to be strongly divergent from the two earlier analysed regions, showing signs of additional distinct populations. Contrasting earlier findings of increased asexual recruitment in low salinity in the Bothnian Sea, we found high levels of sexual reproduction in some of the Gulf of Finland populations that inhabit extremely low salinity. The new data generated in this study supports the earlier conclusion of two reproductively isolated but very closely related species. However, the new results also add considerable genetic and morphological complexity within species. This makes species separation at geographic scales more demanding and suggests a need for more comprehensive approaches to further disentangle the intriguing relationship and history of the Baltic Sea fucoids.

  • 21.
    Arefin, Badrul
    et al.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Kucerova, Lucie
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Krautz, Robert
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Kranenburg, Holger
    Parvin, Farjana
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Theopold, Ulrich
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Apoptosis in Hemocytes Induces a Shift in Effector Mechanisms in the Drosophila Immune System and Leads to a Pro-Inflammatory State2015In: PLOS ONE, E-ISSN 1932-6203, Vol. 10, no 8, article id e0136593Article in journal (Refereed)
    Abstract [en]

    Apart from their role in cellular immunity via phagocytosis and encapsulation, Drosophila hemocytes release soluble factors such as antimicrobial peptides, and cytokines to induce humoral responses. In addition, they participate in coagulation and wounding, and in development. To assess their role during infection with entomopathogenic nematodes, we depleted plasmatocytes and crystal cells, the two classes of hemocytes present in naive larvae by expressing proapoptotic proteins in order to produce hemocyte-free (Hml-apo, originally called Hemo(less)) larvae. Surprisingly, we found that Hml-apo larvae are still resistant to nematode infections. When further elucidating the immune status of Hml-apo larvae, we observe a shift in immune effector pathways including massive lamellocyte differentiation and induction of Toll-as well as repression of imd signaling. This leads to a pro-inflammatory state, characterized by the appearance of melanotic nodules in the hemolymph and to strong developmental defects including pupal lethality and leg defects in escapers. Further analysis suggests that most of the phenotypes we observe in Hml-apo larvae are alleviated by administration of antibiotics and by changing the food source indicating that they are mediated through the microbiota. Biochemical evidence identifies nitric oxide as a key phylogenetically conserved regulator in this process. Finally we show that the nitric oxide donor L-arginine similarly modifies the response against an early stage of tumor development in fly larvae.

  • 22.
    Arnberg, Filip K.
    et al.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Uppsala University, Sweden.
    Michel, Per-Olof
    Lundin, Tom
    Posttraumatic stress in survivors 1 month to 19 years after an airliner emergency landing2015In: PLOS ONE, E-ISSN 1932-6203, Vol. 10, no 3, article id e0119732Article in journal (Refereed)
    Abstract [en]

    Posttraumatic stress (PTS) is common in survivors from life-threatening events. Little is known, however, about the course of PTS after life threat in the absence of collateral stressors (e.g., bereavement, social stigma, property loss) and there is a scarcity of studies about PTS in the long term. This study assessed the short- and long-term course of PTS, and the influence of gender, education and age on the level and course of PTS, in survivors from a non-fatal airliner emergency landing caused by engine failure at an altitude of 1 km. There were 129 persons on board. A survey including the Impact of Event Scale was distributed to 106 subjects after 1 month, 4 months, 14 months, and 25 months, and to 95 subjects after 19 years (response rates 64-83%). There were initially high levels of PTS. The majority of changes in PTS occurred from 1 to 4 months after the event. There were small changes from 4 to 25 months but further decrease in PTS thereafter. Female gender was associated with higher levels of PTS whereas gender was unrelated to the slope of the short- and long-term trajectories. Higher education was related to a quicker recovery although not to initial or long-term PTS. Age was not associated with PTS. The present findings suggest that a life-threatening experience without collateral stressors may produce high levels of acute posttraumatic stress, yet with a benign prognosis. The findings further implicate that gender is unrelated to trajectories of recovery in the context of highly similar exposure and few collateral stressors.

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  • 23.
    Arnell, Matilda
    et al.
    Stockholm University, Faculty of Science, Department of Ecology, Environment and Plant Sciences.
    Cousins, Sara A. O.
    Stockholm University, Faculty of Science, Department of Physical Geography.
    Eriksson, Ove
    Stockholm University, Faculty of Science, Department of Ecology, Environment and Plant Sciences.
    Does historical land use affect the regional distribution of fleshy-fruited woody plants?2019In: PLOS ONE, E-ISSN 1932-6203, Vol. 14, no 12, article id e0225791Article in journal (Refereed)
    Abstract [en]

    Species richness and composition of current vegetation may reflect historical land use. We develop and examine the hypothesis that regional distribution and richness of fleshy-fruited woody plants, a group sharing life-form and dispersal system, reflect historical land use in open or semi-open habitats. Historical land use was based on maps from around the year 1900 for two regions in Sweden, and field data was gathered from surveys made in these regions. Species richness was positively related to historical land use indicated as open habitat in 1900. In one of the regions, five out of nine examined species were positively related to historical land use (with historical effect R-2 ranging between 0.03 and 0.22). In the other region, we found a weaker positive relationship with historical land use in two out of nine examined species (R-2 0.01 and 0.02). We conclude that current occurrence and richness of fleshy-fruited woody species is partly a legacy of historical land use, and that regions may vary in this respect. Based on a comparison between the two regions examined here, we discuss some potential causes behind this variation.

  • 24. Asmat, Tauseef M.
    et al.
    Tenenbaum, Tobias
    Jonsson, Ann-Beth
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Schwerk, Christian
    Schroten, Horst
    Impact of Calcium Signaling during Infection of Neisseria meningitidis to Human Brain Microvascular Endothelial Cells2014In: PLOS ONE, E-ISSN 1932-6203, Vol. 9, no 12, p. e114474-Article in journal (Refereed)
    Abstract [en]

    The pili and outer membrane proteins of Neisseria meningitidis (meningococci) facilitate bacterial adhesion and invasion into host cells. In this context expression of meningococcal PilC1 protein has been reported to play a crucial role. Intracellular calcium mobilization has been implicated as an important signaling event during internalization of several bacterial pathogens. Here we employed time lapse calcium-imaging and demonstrated that PilC1 of meningococci triggered a significant increase in cytoplasmic calcium in human brain microvascular endothelial cells, whereas PilC1-deficient meningococci could not initiate this signaling process. The increase in cytosolic calcium in response to PilC1-expressing meningococci was due to efflux of calcium from host intracellular stores as demonstrated by using 2-APB, which inhibits the release of calcium from the endoplasmic reticulum. Moreover, pre-treatment of host cells with U73122 (phospholipase C inhibitor) abolished the cytosolic calcium increase caused by PilC1-expressing meningococci demonstrating that active phospholipase C (PLC) is required to induce calcium transients in host cells. Furthermore, the role of cytosolic calcium on meningococcal adherence and internalization was documented by gentamicin protection assay and double immunofluorescence (DIF) staining. Results indicated that chelation of intracellular calcium by using BAPTA-AM significantly impaired PilC1-mediated meningococcal adherence to and invasion into host endothelial cells. However, buffering of extracellular calcium by BAPTA or EGTA demonstrated no significant effect on meningococcal adherence to and invasion into host cells. Taken together, these results indicate that meningococci induce calcium release from intracellular stores of host endothelial cells via PilC1 and cytoplasmic calcium concentrations play a critical role during PilC1 mediated meningococcal adherence to and subsequent invasion into host endothelial cells.

  • 25. Asperholm, Martin
    et al.
    Nagar, Sanket
    Dekhtyar, Serhiy
    Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
    Herlitz, Agneta
    The magnitude of sex differences in verbal episodic memory increases with social progress: Data from 54 countries across 40 years2019In: PLOS ONE, E-ISSN 1932-6203, Vol. 14, no 4, article id e0214945Article in journal (Refereed)
    Abstract [en]

    Sex differences in episodic memory have been reported. We investigate (1) the existence of sex differences in verbal and other episodic memory tasks in 54 countries, and (2) the association between the time-and country-specific social progress indicators (a) female to male ratio in education and labor force participation, (b) population education and employment, and (c) GDP per capita, and magnitude of sex differences in verbal episodic memory tasks. Data were retrieved from 612 studies, published 1973-2013. Results showed that females outperformed (Cohen's d > 0) males in verbal (42 out of 45 countries) and other (28 out of 45 countries) episodic memory tasks. Although all three social progress indicators were, separately, positively associated with the female advantage in verbal episodic memory performance, only population education and employment remained significant when considering the social indicators together. Results suggest that women's verbal episodic memory performance benefits more than men's from education and employment.

  • 26.
    Asplund-Samuelsson, Johannes
    et al.
    Stockholm University, Faculty of Science, Department of Botany.
    Bergman, Birgitta
    Stockholm University, Faculty of Science, Department of Botany.
    Larsson, John
    Stockholm University, Faculty of Science, Department of Botany.
    Prokaryotic Caspase Homologs: Phylogenetic Patterns and Functional Characteristics Reveal Considerable Diversity2012In: PLOS ONE, E-ISSN 1932-6203, Vol. 7, no 11, p. e49888-Article in journal (Refereed)
    Abstract [en]

    Caspases accomplish initiation and execution of apoptosis, a programmed cell death process specific to metazoans. The existence of prokaryotic caspase homologs, termed metacaspases, has been known for slightly more than a decade. Despite their potential connection to the evolution of programmed cell death in eukaryotes, the phylogenetic distribution and functions of these prokaryotic metacaspase sequences are largely uncharted, while a few experiments imply involvement in programmed cell death. Aiming at providing a more detailed picture of prokaryotic caspase homologs, we applied a computational approach based on Hidden Markov Model search profiles to identify and functionally characterize putative metacaspases in bacterial and archaeal genomes. Out of the total of 1463 analyzed genomes, merely 267 (18%) were identified to contain putative metacaspases, but their taxonomic distribution included most prokaryotic phyla and a few archaea (Euryarchaeota). Metacaspases were particularly abundant in Alphaproteobacteria, Deltaproteobacteria and Cyanobacteria, which harbor many morphologically and developmentally complex organisms, and a distinct correlation was found between abundance and phenotypic complexity in Cyanobacteria. Notably, Bacillus subtilis and Escherichia coli, known to undergo genetically regulated autolysis, lacked metacaspases. Pfam domain architecture analysis combined with operon identification revealed rich and varied configurations among the metacaspase sequences. These imply roles in programmed cell death, but also e.g. in signaling, various enzymatic activities and protein modification. Together our data show a wide and scattered distribution of caspase homologs in prokaryotes with structurally and functionally diverse subgroups, and with a potentially intriguing evolutionary role. These features will help delineate future characterizations of death pathways in prokaryotes.

  • 27. Assadi, Ghazaleh
    et al.
    Vesterlund, Liselotte
    Bonfiglio, Ferdinando
    Mazzurana, Luca
    Cordeddu, Lina
    Schepis, Danika
    Mjösberg, Jenny
    Ruhrmann, Sabrina
    Fabbri, Alessia
    Vukojevic, Vladana
    Percipalle, Piergiorgio
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. New York University Abu Dhabi, United Arab Emirates.
    Salomons, Florian A.
    Laurencikiene, Jurga
    Törkvist, Leif
    Halfvarson, Jonas
    D'Amato, Mauro
    Functional Analyses of the Crohn's Disease Risk Gene LACC12016In: PLOS ONE, E-ISSN 1932-6203, Vol. 11, no 12, article id e0168276Article in journal (Refereed)
    Abstract [en]

    Background Genetic variation in the Laccase (multicopper oxidoreductase) domain-containing 1 (LACC1) gene has been shown to affect the risk of Crohn's disease, leprosy and, more recently, ulcerative colitis and juvenile idiopathic arthritis. LACC1 function appears to promote fatty-acid oxidation, with concomitant inflammasome activation, reactive oxygen species production, and anti-bacterial responses in macrophages. We sought to contribute to elucidating LACC1 biological function by extensive characterization of its expression in human tissues and cells, and through preliminary analyses of the regulatory mechanisms driving such expression. Methods We implemented Western blot, quantitative real-time PCR, immunofluorescence microscopy, and flow cytometry analyses to investigate fatty acid metabolism-immune nexus (FAMIN; the LACC1 encoded protein) expression in subcellular compartments, cell lines and relevant human tissues. Gene-set enrichment analyses were performed to initially investigate modulatory mechanisms of LACC1 expression. A small-interference RNA knockdown in vitro model system was used to study the effect of FAMIN depletion on peroxisome function. Results FAMIN expression was detected in macrophage-differentiated THP-1 cells and several human tissues, being highest in neutrophils, monocytes/macrophages, myeloid and plasmacytoid dendritic cells among peripheral blood cells. Subcellular co-localization was exclusively confined to peroxisomes, with some additional positivity for organelle endomembrane structures. LACC1 co-expression signatures were enriched for genes involved in peroxisome proliferator-activated receptors (PPAR) signaling pathways, and PPAR ligands downregulated FAMIN expression in in vitro model systems. Conclusion FAMIN is a peroxisome-associated protein with primary role(s) in macrophages and other immune cells, where its metabolic functions may be modulated by PPAR signaling events. However, the precise molecular mechanisms through which FAMIN exerts its biological effects in immune cells remain to be elucidated.

  • 28.
    Attoff, Kristina
    et al.
    Stockholm University, Faculty of Science, Department of Neurochemistry.
    Gliga, Anda
    Lundqvist, Jessica
    Stockholm University, Faculty of Science, Department of Neurochemistry. Swetox, Karolinska Institutet, Sweden.
    Norinder, Ulf
    Forsby, Anna
    Stockholm University, Faculty of Science, Department of Neurochemistry. Swetox, Karolinska Institutet, Sweden.
    Whole genome microarray analysis of neural progenitor C17.2 cells during differentiation and validation of 30 neural mRNA biomarkers for estimation of developmental neurotoxicity2017In: PLOS ONE, E-ISSN 1932-6203, Vol. 12, no 12, article id e0190066Article in journal (Refereed)
    Abstract [en]

    Despite its high relevance, developmental neurotoxicity (DNT) is one of the least studied forms of toxicity. Current guidelines for DNT testing are based on in vivo testing and they require extensive resources. Transcriptomic approaches using relevant in vitro models have been suggested as a useful tool for identifying possible DNT-generating compounds. In this study, we performed whole genome microarray analysis on the murine progenitor cell line C17.2 following 5 and 10 days of differentiation. We identified 30 genes that are strongly associated with neural differentiation. The C17.2 cell line can be differentiated into a co-culture of both neurons and neuroglial cells, giving a more relevant picture of the brain than using neuronal cells alone. Among the most highly upregulated genes were genes involved in neurogenesis (CHRDL1), axonal guidance (BMP4), neuronal connectivity (PLXDC2), axonogenesis (RTN4R) and astrocyte differentiation (S100B). The 30 biomarkers were further validated by exposure to non-cytotoxic concentrations of two DNT-inducing compounds (valproic acid and methylmercury) and one neurotoxic chemical possessing a possible DNT activity (acrylamide). Twenty-eight of the 30 biomarkers were altered by at least one of the neurotoxic substances, proving the importance of these biomarkers during differentiation. These results suggest that gene expression profiling using a predefined set of biomarkers could be used as a sensitive tool for initial DNT screening of chemicals. Using a predefined set of mRNA biomarkers, instead of the whole genome, makes this model affordable and high-throughput. The use of such models could help speed up the initial screening of substances, possibly indicating alerts that need to be further studied in more sophisticated models.

  • 29.
    Audusseau, Hélène
    et al.
    Stockholm University, Faculty of Science, Department of Zoology.
    Kolb, Gundula
    Stockholm University, Faculty of Science, Department of Ecology, Environment and Plant Sciences.
    Janz, Niklas
    Stockholm University, Faculty of Science, Department of Zoology.
    Plant Fertilization Interacts with Life History: Variation in Stoichiometry and Performance in Nettle-Feeding Butterflies2015In: PLOS ONE, E-ISSN 1932-6203, Vol. 10, no 5, article id e0124616Article in journal (Refereed)
    Abstract [en]

    Variation in food stoichiometry affects individual performance and population dynamics, but it is also likely that species with different life histories should differ in their sensitivity to food stoichiometry. To address this question, we investigated the ability of the three nettle-feeding butterflies (Aglais urticae, Polygonia c-album, and Aglais io) to respond adaptively to induced variation in plant stoichiometry in terms of larval performance. We hypothesized that variation in larval performance between plant fertilization treatments should be functionally linked to species differences in host plant specificity. We found species-specific differences in larval performance between plant fertilization treatments that could not be explained by nutrient limitation. We showed a clear evidence of a positive correlation between food stoichiometry and development time to pupal stage and pupal mass in Aglais urticae. The other two species showed a more complex response. Our results partly supported our prediction that host plant specificity affects larval sensitivity to food stoichiometry. However, we suggest that most of the differences observed may instead be explained by differences in voltinism (number of generations per year). We believe that the potential of some species to respond adaptively to variation in plant nutrient content needs further attention in the face of increased eutrophication due to nutrient leakage from human activities.

  • 30.
    Auffret, Alistair G.
    et al.
    Stockholm University, Faculty of Science, Department of Physical Geography and Quaternary Geology.
    Cousins, Sara A. O.
    Stockholm University, Faculty of Science, Department of Physical Geography and Quaternary Geology.
    Humans as Long-Distance Dispersers of Rural Plant Communities2013In: PLOS ONE, E-ISSN 1932-6203, Vol. 8, no 5, article id e62763Article in journal (Refereed)
    Abstract [en]

    Humans are known for their capacity to disperse organisms long distances. Long-distance dispersal can be important for species threatened by habitat destruction, but research into human-mediated dispersal is often focused upon few and/or invasive species. Here we use citizen science to identify the capacity for humans to disperse seeds on their clothes and footwear from a known species pool in a valuable habitat, allowing for an assessment of the fraction and types of species dispersed by humans in an alternative context. We collected material from volunteers cutting 48 species-rich meadows throughout Sweden. We counted 24 354 seeds of 197 species, representing 34% of the available species pool, including several rare and protected species. However, 71 species (36%) are considered invasive elsewhere in the world. Trait analysis showed that seeds with hooks or other appendages were more likely to be dispersed by humans, as well as those with a persistent seed bank. More activity in a meadow resulted in more dispersal, both in terms of species and representation of the source communities. Average potential dispersal distances were measured at 13 km. We consider humans capable seed dispersers, transporting a significant proportion of the plant communities in which they are active, just like more traditional vectors such as livestock. When rural populations were larger, people might have been regular and effective seed dispersers, and the net rural-urban migration resulting in a reduction in humans in the landscape may have exacerbated the dispersal failure evident in declining plant populations today. With the fragmentation of habitat and changes in land use resulting from agricultural change, and the increased mobility of humans worldwide, the dispersal role of humans may have shifted from providers of regular local and landscape dispersal to providers of much rarer long-distance and regional dispersal, and international invasion.

  • 31. Aurelius, Oskar
    et al.
    Johansson, Renzo
    Bågenholm, Viktoria
    Lundin, Daniel
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Tholander, Fredrik
    Balhuizen, Alexander
    Beck, Tobias
    Sahlin, Margareta
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Sjöberg, Britt-Marie
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Mulliez, Etienne
    Logan, Derek T.
    The Crystal Structure of Thermotoga maritima Class III Ribonucleotide Reductase Lacks a Radical Cysteine Pre-Positioned in the Active Site2015In: PLOS ONE, 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.

  • 32.
    Austin, Åsa N.
    et al.
    Stockholm University, Faculty of Science, Department of Ecology, Environment and Plant Sciences.
    Hansen, Joakim P.
    Stockholm University, Faculty of Science, Stockholm University Baltic Sea Centre.
    Donadi, Serena
    Stockholm University, Faculty of Science, Department of Ecology, Environment and Plant Sciences.
    Eklöf, Johan
    Stockholm University, Faculty of Science, Department of Ecology, Environment and Plant Sciences.
    Relationships between aquatic vegetation and water turbidity: A field survey across seasons and spatial scales2017In: PLOS ONE, E-ISSN 1932-6203, Vol. 12, no 8, article id e0181419Article in journal (Refereed)
    Abstract [en]

    Field surveys often show that high water turbidity limits cover of aquatic vegetation, while many small-scale experiments show that vegetation can reduce turbidity by decreasing water flow, stabilizing sediments, and competing with phytoplankton for nutrients. Here we bridged these two views by exploring the direction and strength of causal relationships between aquatic vegetation and turbidity across seasons (spring and late summer) and spatial scales (local and regional), using causal modeling based on data from a field survey along the central Swedish Baltic Sea coast. The two best-fitting regional-scale models both suggested that in spring, high cover of vegetation reduces water turbidity. In summer, the relationships differed between the two models; in the first model high vegetation cover reduced turbidity; while in the second model reduction of summer turbidity by high vegetation cover in spring had a positive effect on summer vegetation which suggests a positive feedback of vegetation on itself. Nitrogen load had a positive effect on turbidity in both seasons, which was comparable in strength to the effect of vegetation on turbidity. To assess whether the effect of vegetation was primarily caused by sediment stabilization or a reduction of phytoplankton, we also tested models where turbidity was replaced by phytoplankton fluorescence or sediment-driven turbidity. The best-fitting regional-scale models suggested that high sediment-driven turbidity in spring reduces vegetation cover in summer, which in turn has a negative effect on sediment-driven turbidity in summer, indicating a potential positive feedback of sediment-driven turbidity on itself. Using data at the local scale, few relationships were significant, likely due to the influence of unmeasured variables and/or spatial heterogeneity. In summary, causal modeling based on data from a large-scale field survey suggested that aquatic vegetation can reduce turbidity at regional scales, and that high vegetation cover vs. high sediment-driven turbidity may represent two self-enhancing, alternative states of shallow bay ecosystems.

  • 33.
    Axelsson, John
    et al.
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska Institutet, Sweden.
    Rehman, Javaid-ur
    Åkerstedt, Torbjörn
    Stockholm University, Faculty of Social Sciences, Stress Research Institute.
    Ekman, Rolf
    Miller, Gregory E.
    Höglund, Caroline Olgart
    Lekander, Mats
    Stockholm University, Faculty of Social Sciences, Stress Research Institute. Karolinska institutet, Sweden.
    Effects of Sustained Sleep Restriction on Mitogen-Stimulated Cytokines, Chemokines and T Helper 1/ T Helper 2 Balance in Humans2013In: PLOS ONE, E-ISSN 1932-6203, Vol. 8, no 12, article id e82291Article in journal (Refereed)
    Abstract [en]

    Background: Recent studies suggest that acute sleep deprivation disrupts cellular immune responses by shifting T helper (Th) cell activity towards a Th2 cytokine profile. Since little is known about more long-term effects, we investigated how five days of sleep restriction would affect pro-inflammatory, chemotactic, Th1- and Th2 cytokine secretion. Methods: Nine healthy males participated in an experimental sleep protocol with two baseline sleep-wake cycles (sleep 23.00 - 07.00 h) followed by 5 days with restricted sleep (03.00 - 07.00 h). On the second baseline day and on the fifth day with restricted sleep, samples were drawn every third hour for determination of cytokines/chemokines (tumor necrosis factor alpha (TNF-alpha), interleukin (IL) -1 beta, IL-2, IL-4 and monocyte chemoattractant protein-1 (MCP-1)) after in vitro stimulation of whole blood samples with the mitogen phytohemagglutinin (PHA). Also leukocyte numbers, mononuclear cells and cortisol were analysed. Results: 5-days of sleep restriction affected PHA-induced immune responses in several ways. There was a general decrease of IL-2 production (p<.05). A shift in Th1/Th2 cytokine balance was also evident, as determined by a decrease in IL2/IL4 ratio. No other main effects of restricted sleep were shown. Two significant interactions showed that restricted sleep resulted in increased TNF-alpha and MCP-1 in the late evening and early night hours (p's<.05). In addition, all variables varied across the 24 h day. Conclusions: 5-days of sleep restriction is characterized by a shift towards Th2 activity (i.e. lower 1L-2/IL-4 ratio) which is similar to the effects of acute sleep deprivation and psychological stress. This may have implications for people suffering from conditions characterized by excessive Th2 activity like in allergic disease, such as asthma, for whom restricted sleep could have negative consequences.

  • 34. Babini, Gabriele
    et al.
    Baiocco, Giorgio
    Barbieri, Sofia
    Morini, Jacopo
    Sangsuwan, Traimate
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Haghdoost, Siamak
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. University of Caen Normandy, France.
    Yentrapalli, Ramesh
    Azimzadeh, Omid
    Rombouts, Charlotte
    Aerts, An
    Quintens, Roel
    Ebrahimian, Teni
    Benotmane, Mohammed Abderrafi
    Ramadan, Raghda
    Baatout, Sarah
    Tapio, Soile
    Harms-Ringdahl, Mats
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Ottolenghi, Andrea
    A systems radiation biology approach to unravel the role of chronic low-dose-rate gamma-irradiation in inducing premature senescence in endothelial cells2022In: PLOS ONE, E-ISSN 1932-6203, Vol. 17, no 3, article id e0265281Article in journal (Refereed)
    Abstract [en]

    Purpose

    The aim of this study was to explore the effects of chronic low-dose-rate gamma-radiation at a multi-scale level. The specific objective was to obtain an overall view of the endothelial cell response, by integrating previously published data on different cellular endpoints and highlighting possible different mechanisms underpinning radiation-induced senescence.

    Materials and methods

    Different datasets were collected regarding experiments on human umbilical vein endothelial cells (HUVECs) which were chronically exposed to low dose rates (0, 1.4, 2.1 and 4.1 mGy/h) of gamma-rays until cell replication was arrested. Such exposed cells were analyzed for different complementary endpoints at distinct time points (up to several weeks), investigating cellular functions such as proliferation, senescence and angiogenic properties, as well as using transcriptomics and proteomics profiling. A mathematical model was proposed to describe proliferation and senescence.

    Results

    Simultaneous ceasing of cell proliferation and senescence onset as a function of time were well reproduced by the logistic growth curve, conveying shared equilibria between the two endpoints. The combination of all the different endpoints investigated highlighted a dose-dependence for prematurely induced senescence. However, the underpinning molecular mechanisms appeared to be dissimilar for the different dose rates, thus suggesting a more complex scenario.

    Conclusions

    This study was conducted integrating different datasets, focusing on their temporal dynamics, and using a systems biology approach. Results of our analysis highlight that different dose rates have different effects in inducing premature senescence, and that the total cumulative absorbed dose also plays an important role in accelerating endothelial cell senescence.

  • 35. Bagger-Sjöbäck, Dan
    et al.
    Strömbäck, Karin
    Hakizimana, Pierre
    Plue, Jan
    Stockholm University, Faculty of Science, Department of Physical Geography.
    Larsson, Christina
    Hultcrantz, Malou
    Papatziamos, Georgios
    Smeds, Henrik
    Danckwardt-Lillieström, Niklas
    Hellström, Sten
    Johansson, Ann
    Tideholm, Bo
    Fridberger, Anders
    A Randomised, Double Blind Trial of N-Acetylcysteine for Hearing Protection during Stapes Surgery2015In: PLOS ONE, E-ISSN 1932-6203, Vol. 10, no 3, article id e0115657Article in journal (Refereed)
    Abstract [en]

    Background Otosclerosis is a disorder that impairs middle ear function, leading to conductive hearing loss. Surgical treatment results in large improvement of hearing at low sound frequencies, but high-frequency hearing often suffers. A likely reason for this is that inner ear sensory cells are damaged by surgical trauma and loud sounds generated during the operation. Animal studies have shown that antioxidants such as N-Acetylcysteine can protect the inner ear from noise, surgical trauma, and some ototoxic substances, but it is not known if this works in humans. This trial was performed to determine whether antioxidants improve surgical results at high frequencies. Methods We performed a randomized, double-blind and placebo-controlled parallel group clinical trial at three Swedish university clinics. Using block-stratified randomization, 156 adult patients undergoing stapedotomy were assigned to intravenous N-Acetylcysteine (150 mg/kg body weight) or matching placebo (1:1 ratio), starting one hour before surgery. The primary outcome was the hearing threshold at 6 and 8 kHz; secondary outcomes included the severity of tinnitus and vertigo. Findings One year after surgery, high-frequency hearing had improved 2.7 +/- 3.8 dB in the placebo group (67 patients analysed) and 2.4 +/- 3.7 dB in the treated group (72 patients; means +/- 95% confidence interval, p = 0.54; linear mixed model). Surgery improved tinnitus, but there was no significant intergroup difference. Post-operative balance disturbance was common but improved during the first year, without significant difference between groups. Four patients receiving N-Acetylcysteine experienced mild side effects such as nausea and vomiting. Conclusions N-Acetylcysteine has no effect on hearing thresholds, tinnitus, or balance disturbance after stapedotomy.

  • 36.
    Balk, Lennart
    et al.
    Stockholm University, Faculty of Science, Department of Applied Environmental Science (ITM).
    Hylland, Ketil
    Hansson, Tomas
    Stockholm University, Faculty of Science, Department of Applied Environmental Science (ITM).
    Berntssen, Marc H. G.
    Beyer, Jonny
    Jonsson, Grete
    Melbye, Alf
    Grung, Merete
    Torstensen, Bente E.
    Borseth, Jan Fredrik
    Skarphedinsdottir, Halldora
    Stockholm University, Faculty of Science, Department of Applied Environmental Science (ITM).
    Klungsoyr, Jarle
    Biomarkers in Natural Fish Populations Indicate Adverse Biological Effects of Offshore Oil Production2011In: PLOS ONE, E-ISSN 1932-6203, Vol. 6, no 5, p. e19735-Article in journal (Refereed)
    Abstract [en]

    Background: Despite the growing awareness of the necessity of a sustainable development, the global economy continues to depend largely on the consumption of non-renewable energy resources. One such energy resource is fossil oil extracted from the seabed at offshore oil platforms. This type of oil production causes continuous environmental pollution from drilling waste, discharge of large amounts of produced water, and accidental spills. Methods and principal findings: Samples from natural populations of haddock (Melanogrammus aeglefinus) and Atlantic cod (Gadus morhua) in two North Sea areas with extensive oil production were investigated. Exposure to and uptake of polycyclic aromatic hydrocarbons (PAHs) were demonstrated, and biomarker analyses revealed adverse biological effects, including induction of biotransformation enzymes, oxidative stress, altered fatty acid composition, and genotoxicity. Genotoxicity was reflected by a hepatic DNA adduct pattern typical for exposure to a mixture of PAHs. Control material was collected from a North Sea area without oil production and from remote Icelandic waters. The difference between the two control areas indicates significant background pollution in the North Sea. Conclusion: It is most remarkable to obtain biomarker responses in natural fish populations in the open sea that are similar to the biomarker responses in fish from highly polluted areas close to a point source. Risk assessment of various threats to the marine fish populations in the North Sea, such as overfishing, global warming, and eutrophication, should also take into account the ecologically relevant impact of offshore oil production.

  • 37. Banack, Sandra Anne
    et al.
    Metcalf, James S.
    Jiang, Liying
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Craighead, Derek
    Ilag, Leopold L.
    Stockholm University, Faculty of Science, Department of Analytical Chemistry.
    Cox, Paul Alan
    Cyanobacteria Produce N-(2-Aminoethyl)Glycine, a Backbone for Peptide Nucleic Acids Which May Have Been the First Genetic Molecules for Life on Earth2012In: PLOS ONE, E-ISSN 1932-6203, Vol. 7, no 11, p. e49043-Article in journal (Refereed)
    Abstract [en]

    Prior to the evolution of DNA-based organisms on earth over 3.5 billion years ago it is hypothesized that RNA was the primary genetic molecule. Before RNA-based organisms arose, peptide nucleic acids may have been used to transmit genetic information by the earliest forms of life on earth. We discovered that cyanobacteria produce N-(2-aminoethyl)glycine (AEG), a backbone for peptide nucleic acids. We detected AEG in axenic strains of cyanobacteria with an average concentration of 1 µg/g. We also detected AEG in environmental samples of cyanobacteria as both a free or weakly bound molecule and a tightly bound form released by acid hydrolysis, at concentrations ranging from not detected to 34 µg/g. The production of AEG by diverse taxa of cyanobacteria suggests that AEG may be a primitive feature which arose early in the evolution of life on earth

  • 38. Barbeiro, A. R.
    et al.
    Ureba, Ana
    Stockholm University, Faculty of Science, Department of Physics. Universidad de Sevilla, Spain; Instituto de Biomedicina de Sevilla, IBIS, Spain; Karolinska Institutet, Sweden.
    Baeza, J. A.
    Linares, R.
    Perucha, M.
    Jimenez-Ortega, E.
    Velazquez, S.
    Mateos, J. C.
    Leal, A.
    3D VMAT Verification Based on Monte Carlo Log File Simulation with Experimental Feedback from Film Dosimetry2016In: PLOS ONE, E-ISSN 1932-6203, Vol. 11, no 11, article id e0166767Article in journal (Refereed)
    Abstract [en]

    A model based on a specific phantom, called QuAArC, has been designed for the evaluation of planning and verification systems of complex radiotherapy treatments, such as volumetric modulated arc therapy (VMAT). This model uses the high accuracy provided by the Monte Carlo (MC) simulation of log files and allows the experimental feedback from the high spatial resolution of films hosted in QuAArC. This cylindrical phantom was specifically designed to host films rolled at different radial distances able to take into account the entrance fluence and the 3D dose distribution. Ionization chamber measurements are also included in the feedback process for absolute dose considerations. In this way, automated MC simulation of treatment log files is implemented to calculate the actual delivery geometries, while the monitor units are experimentally adjusted to reconstruct the dose-volume histogram (DVH) on the patient CT. Prostate and head and neck clinical cases, previously planned with Monaco and Pinnacle treatment planning systems and verified with two different commercial systems (Delta4 and COMPASS), were selected in order to test operational feasibility of the proposed model. The proper operation of the feedback procedure was proved through the achieved high agreement between reconstructed dose distributions and the film measurements (global gamma passing rates > 90% for the 2%/2 mm criteria). The necessary discretization level of the log file for dose calculation and the potential mismatching between calculated control points and detection grid in the verification process were discussed. Besides the effect of dose calculation accuracy of the analytic algorithm implemented in treatment planning systems for a dynamic technique, it was discussed the importance of the detection density level and its location in VMAT specific phantom to obtain a more reliable DVH in the patient CT. The proposed model also showed enough robustness and efficiency to be considered as a pre-treatment VMAT verification system.

  • 39. Basurto, Xavier
    et al.
    Bennett, Abigail
    Lindkvist, Emilie
    Stockholm University, Faculty of Science, Stockholm Resilience Centre.
    Schlüter, Maja
    Stockholm University, Faculty of Science, Stockholm Resilience Centre.
    Governing the commons beyond harvesting: An empirical illustration from fishing2020In: PLOS ONE, E-ISSN 1932-6203, Vol. 15, no 4, article id e0231575Article in journal (Refereed)
    Abstract [en]

    Harvesting has received most theoretical, empirical, and policy attention towards understanding common-pool resource dilemmas. Yet, pre-harvesting and post-harvesting activities influence harvesting outcomes as well. Broadening the analytical focus beyond harvesting is needed to imagine new ways of theorizing and governing the commons. Fishing-which is synonymous with harvesting-is a case in point. We contribute to a beyond-harvesting research agenda by incorporating concepts from common-pool resources theory that have not received enough attention in the literature. We compare two ubiquitous self-organizing strategies (i.e., fishing cooperatives and patron-client relationships) fishers use to access means of production and analyze their effects on the distribution of benefits resulting from harvesting. We use rarely available longitudinal data of monetary loans to fishers in Mexican small-scale fisheries and find that cooperatives can deliver broader distribution of benefits than patron-client relationships. Our study highlights the importance of historically and contextually situating analyses linking the effects of pre-harvesting processes on harvesting outcomes, and the benefits of broadening the scope of inquiry beyond a narrow policy attention on harvesting to move towards a fuller understanding of commons dilemmas.

  • 40.
    Bauer, Barbara
    et al.
    Stockholm University, Faculty of Science, Stockholm University Baltic Sea Centre. German Centre for Integrative Biodiversity Research (iDiv), Germany.
    Horbowy, Jan
    Rahikainen, Mika
    Kulatska, Nataliia
    Müller-Karulis, Bärbel
    Stockholm University, Faculty of Science, Stockholm University Baltic Sea Centre.
    Tomczak, Maciej T.
    Stockholm University, Faculty of Science, Stockholm University Baltic Sea Centre.
    Bartolino, Valerio
    Model uncertainty and simulated multispecies fisheries management advice in the Baltic Sea2019In: PLOS ONE, E-ISSN 1932-6203, Vol. 14, no 1, article id e0211320Article in journal (Refereed)
    Abstract [en]

    Different ecosystem models often provide contrasting predictions (model uncertainty), which is perceived to be a major challenge impeding their use to support ecosystem-based fisheries management (EBFM). The focus of this manuscript is to examine the extent of model disagreements which could impact management advice for EBFM in the central Baltic Sea. We compare how much three models (EwE, Gadget and a multispecies stock production model) differ in 1) their estimates of fishing mortality rates (Fs) satisfying alternative hypothetical management scenario objectives and 2) the outcomes of those scenarios in terms of performance indicators (spawning stock biomasses, catches, profits). Uncertainty in future environmental conditions affecting fish was taken into account by considering two seal population growth scenarios and two nutrient load scenarios. Differences in the development of the stocks, yields and profits exist among the models but the general patterns are also sufficiently similar to appear promising in the context of strategic fishery advice. Thus, we suggest that disagreements among the ecosystem models will not impede their use for providing strategic advice on how to reach management objectives that go beyond the traditional maximum yield targets and for informing on the potential consequences of pursuing such objectives. This is especially true for scenarios aiming at exploiting forage fish sprat and herring, for which the agreement was the largest among our models. However, the quantitative response to altering fishing pressure differed among models. This was due to the diverse environmental covariates and the different number of trophic relationships and their functional forms considered in the models. This suggests that ecosystem models can be used to provide quantitative advice only after more targeted research is conducted to gain a deeper understanding into the relationship between trophic links and fish population dynamics in the Baltic Sea.

  • 41.
    Bauer, Stefanie L.
    et al.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Chen, Jiang
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Åström, Stefan U.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Helicase/SUMO-targeted ubiquitin ligase Uls1 interacts with the Holliday junction resolvase Yen12019In: PLOS ONE, E-ISSN 1932-6203, Vol. 14, no 3, article id e0214102Article in journal (Refereed)
    Abstract [en]

    Resolution of branched DNA structures is pivotal for repair of stalled replication forks and meiotic recombination intermediates. The Yen1 nuclease cleaves both Holliday junctions and replication forks. We show that Yen1 interacts physically with Uls1, a suggested SUMO-targeted ubiquitin ligase that also contains a SWI/SNF-family ATPase-domain. Yen1 is SUMO-modified in its noncatalytic carboxyl terminus and DNA damage induces SUMOylation. SUMO-modification of Yen1 strengthens the interaction to Uls1, and mutations in SUMO interaction motifs in Uls1 weakens the interaction. However, Uls1 does not regulate the steady-state level of SUMO-modified Yen1 or chromatin-associated Yen1. In addition, SUMO-modification of Yen1 does not affect the catalytic activity in vitro. Consistent with a shared function for Uls1 and Yen1, mutations in both genes display similar phenotypes. Both uls1 and yen1 display negative genetic interactions with the alternative HJ-cleaving nuclease Mus81, manifested both in hypersensitivity to DNA damaging agents and in meiotic defects. Point mutations in ULS1 (uls1K975R and uls1C1330S, C1333S) predicted to inactivate the ATPase and ubiquitin ligase activities, respectively, are as defective as the null allele, indicating that both functions of Uls1 are essential. A micrococcal nuclease sequencing experiment showed that Uls1 had minimal effects on global nucleosome positioning/occupancy. Moreover, increased gene dosage of YEN1 partially alleviates the mus81 uls1 sensitivity to DNA damage. We suggest a preliminary model in which Uls1 acts in the same pathway as Yen1 to resolve branched DNA structures.

  • 42. Becnel, Jaime
    et al.
    Johnson, Oralee
    Luo, Jiangnan
    Stockholm University, Faculty of Science, Department of Zoology.
    Nässel, Dick R.
    Stockholm University, Faculty of Science, Department of Zoology.
    Nichols, Charles D.
    The Serotonin 5-HT(7)Dro Receptor Is Expressed in the Brain of Drosophila, and Is Essential for Normal Courtship and Mating2011In: PLOS ONE, E-ISSN 1932-6203, Vol. 6, no 6, p. e20800-Article in journal (Refereed)
    Abstract [en]

    The 5-HT(7) receptor remains one of the less well characterized serotonin receptors. Although it has been demonstrated to be involved in the regulation of mood, sleep, and circadian rhythms, as well as relaxation of vascular smooth muscles in mammals, the precise mechanisms underlying these functions remain largely unknown. The fruit fly, Drosophila melanogaster, is an attractive model organism to study neuropharmacological, molecular, and behavioral processes that are largely conserved with mammals. Drosophila express a homolog of the mammalian 5-HT(7) receptor, as well as homologs for the mammalian 5-HT(1A), and 5-HT(2), receptors. Each fly receptor couples to the same effector pathway as their mammalian counterpart and have been demonstrated to mediate similar behavioral responses. Here, we report on the expression and function of the 5-HT(7)Dro receptor in Drosophila. In the larval central nervous system, expression is detected postsynaptically in discreet cells and neuronal circuits. In the adult brain there is strong expression in all large-field R neurons that innervate the ellipsoid body, as well as in a small group of cells that cluster with the PDF-positive LNvs neurons that mediate circadian activity. Following both pharmacological and genetic approaches, we have found that 5-HT(7)Dro activity is essential for normal courtship and mating behaviors in the fly, where it appears to mediate levels of interest in both males and females. This is the first reported evidence of direct involvement of a particular serotonin receptor subtype in courtship and mating in the fly.

  • 43. Begun, Alexander
    et al.
    Liubimov, Sergei
    Molochkov, Alexander
    Niemi, Antti J.
    Stockholm University, Nordic Institute for Theoretical Physics (Nordita). Far Eastern Federal University, Russia; Beijing Institute of Technology, People’s Republic of China.
    On topology and knotty entanglement in protein folding2021In: PLOS ONE, E-ISSN 1932-6203, Vol. 16, no 1, article id e0244547Article in journal (Refereed)
    Abstract [en]

    We investigate aspects of topology in protein folding. For this we numerically simulate the temperature driven folding and unfolding of the slipknotted archaeal virus protein AFV3-109. Due to knottiness the (un)folding is a topological process, it engages the entire backbone in a collective fashion. Accordingly we introduce a topological approach to model the process. Our simulations reveal that the (un)folding of AFV3-109 slipknot proceeds through a folding intermediate that has the topology of a trefoil knot. We observe that the final slipknot causes a slight swelling of the folded AFV3-109 structure. We disclose the relative stability of the strands and helices during both the folding and unfolding processes. We confirm results from previous studies that pointed out that it can be very demanding to simulate the formation of knotty self-entanglement, and we explain how the problems are circumvented: The slipknotted AFV3-109 protein is a very slow folder with a topologically demanding pathway, which needs to be properly accounted for in a simulation description. When we either increase the relative stiffness of bending, or when we decrease the speed of ambient cooling, the rate of slipknot formation rapidly increases.

  • 44.
    Bellander, Theres
    et al.
    Stockholm University, Faculty of Humanities, Department of Swedish Language and Multilingualism, Scandinavian Languages.
    Karlsson, Anna-Malin
    Stockholm University, Faculty of Humanities, Department of Swedish Language and Multilingualism, Scandinavian Languages.
    Patient participation and learning in medical consultations about congenital heart defects2019In: PLOS ONE, E-ISSN 1932-6203, Vol. 14, no 7, article id e0220136Article in journal (Refereed)
    Abstract [en]

    In this article, patient activity in 8 audio recorded specialist consultations on fetal cardiology is investigated in order to explore how, why and when patients tend to participate in encounters in which the doctor dominates the interaction. The overall question is: How can the participation of patients in the consultations be connected to the development of higher levels of health literacy, i.e. to interactive literacy and to critical literacy? Patient participation is here understood as interactive action and is analyzed in terms of different interactive moves, which are related to different recurring topics. Despite the highly standardized format of the consultations, there is a large variation between the patients’ participation: between 0.7 and 2.8 moves per minute. The patients participate most during the topics ‘Prevalence’ and ‘Consultations’ and least during the topic ‘The normal heart’. Although most of the patients' moves are responses to what the doctor says, they remarkably often pose questions and use so called rejoinders. By posing questions, they take control of the information flow and sometimes even change the topics. By using rejoinders, they analyze the problems involved in the discussion e.g. by asking for clarifications or confirmation. Patients with a low over-all participation rate also use fewer moves that indicate higher literacy levels. The qualitative analysis problematizes the idea of a simple scale from basic literacy to critical literacy. Moves that indicate basic literacy skills are interactively important for the learning activity, led by the doctor. However, patients who mainly support the doctor’s initiatives don’t take the opportunity to influence the flow of information in ways that might favor their health literacy development.

  • 45.
    Beltran-Pardo, Eliana
    et al.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Jonsson, K. Ingemar
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. Kristianstad University, Sweden.
    Harms-Ringdahl, Mats
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Haghdoost, Siamak
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Wojcik, Andrzej
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Tolerance to Gamma Radiation in the Tardigrade Hypsibius dujardini from Embryo to Adult Correlate Inversely with Cellular Proliferation2015In: PLOS ONE, E-ISSN 1932-6203, Vol. 10, no 7, article id e0133658Article in journal (Refereed)
    Abstract [en]

    Tardigrades are highly tolerant to desiccation and ionizing radiation but the mechanisms of this tolerance are not well understood. In this paper, we report studies on dose responses of adults and eggs of the tardigrade Hypsibius dujardini exposed to gamma radiation. In adults the LD50/48h for survival was estimated at similar to 4200 Gy, and doses higher than 100 Gy reduced both fertility and hatchability of laid eggs drastically. We also evaluated the effect of radiation (doses 50 Gy, 200 Gy, 500 Gy) on eggs in the early and late embryonic stage of development, and observed a reduced hatchability in the early stage, while no effect was found in the late stage of development. Survival of juveniles from irradiated eggs was highly affected by a 500 Gy dose, both in the early and the late stage. Juveniles hatched from eggs irradiated at 50 Gy and 200 Gy developed into adults and produced offspring, but their fertility was reduced compared to the controls. Finally we measured the effect of low temperature during irradiation at 4000 Gy and 4500 Gy on survival in adult tardigrades, and observed a slight delay in the expressed mortality when tardigrades were irradiated on ice. Since H. dujardini is a freshwater tardigrade with lower tolerance to desiccation compared to limno-terrestrial tardigrades, the high radiation tolerance in adults, similar to limno-terrestrial tardigrades, is unexpected and seems to challenge the idea that desiccation and radiation tolerance rely on the same molecular mechanisms. We suggest that the higher radiation tolerance in adults and late stage embryos of H. dujardini (and in other studied tardigrades) compared to early stage embryos may partly be due to limited mitotic activity, since tardigrades have a low degree of somatic cell division (eutely), and dividing cells are known to be more sensitive to radiation.

  • 46.
    Beltran-Pardo, Eliana
    et al.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. Pontificia Universidad Javeriana, Colombia.
    Jonsson, K. Ingemar
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. Kristianstad University, Sweden.
    Wojcik, Andrzej
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Haghdoost, Siamak
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Harms-Ringdahl, Mats
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Bermudez-Cruz, Rosa M.
    Villegas, Jaime E. Bernal
    Effects of Ionizing Radiation on Embryos of the Tardigrade Milnesium cf. tardigradum at Different Stages of Development2013In: PLOS ONE, E-ISSN 1932-6203, Vol. 8, no 9, article id e72098Article in journal (Refereed)
    Abstract [en]

    Tardigrades represent one of the most desiccation and radiation tolerant animals on Earth, and several studies have documented their tolerance in the adult stage. Studies on tolerance during embryological stages are rare, but differential effects of desiccation and freezing on different developmental stages have been reported, as well as dose-dependent effect of gamma irradiation on tardigrade embryos. Here, we report a study evaluating the tolerance of eggs from the eutardigrade Milnesium cf. tardigradum to three doses of gamma radiation (50, 200 and 500 Gy) at the early, middle, and late stage of development. We found that embryos of the middle and late developmental stages were tolerant to all doses, while eggs in the early developmental stage were tolerant only to a dose of 50 Gy, and showed a declining survival with higher dose. We also observed a delay in development of irradiated eggs, suggesting that periods of DNA repair might have taken place after irradiation induced damage. The delay was independent of dose for eggs irradiated in the middle and late stage, possibly indicating a fixed developmental schedule for repair after induced damage. These results show that the tolerance to radiation in tardigrade eggs changes in the course of their development. The mechanisms behind this pattern are unknown, but may relate to changes in mitotic activities over the embryogenesis and/or to activation of response mechanisms to damaged DNA in the course of development.

  • 47. Bengtsson, Linus
    et al.
    Lu, Xin
    Stockholm University, Faculty of Social Sciences, Department of Sociology.
    Nguyen, Quoc Cuong
    Camitz, Martin
    Hoang, Nguyen Le
    Nguyen, Tuan Anh
    Liljeros, Fredrik
    Stockholm University, Faculty of Social Sciences, Department of Sociology.
    Thorson, Anna
    Implementation of Web-Based Respondent-Driven Sampling among Men Who Have Sex with Men in Vietnam2012In: PLOS ONE, E-ISSN 1932-6203, Vol. 7, no 11, p. e49417-Article in journal (Refereed)
    Abstract [en]

    Objective: Lack of representative data about hidden groups, like men who have sex with men (MSM), hinders an evidence-based response to the HIV epidemics. Respondent-driven sampling (RDS) was developed to overcome sampling challenges in studies of populations like MSM for which sampling frames are absent. Internet-based RDS (webRDS) can potentially circumvent limitations of the original RDS method. We aimed to implement and evaluate webRDS among a hidden population. Methods and Design: criteria were men, aged 18 and above, who had ever had sex with another man and were living in Vietnam. Participants were invited by an MSM friend, logged in, and answered a survey. Participants could recruit up to four MSM friends. We evaluated the system by its success in generating sustained recruitment and the degree to which the sample compositions stabilized with increasing sample size. Results: Twenty starting participants generated 676 participants over 24 recruitment waves. Analyses did not show evidence of bias due to ineligible participation. Estimated mean age was 22 years and 82% came from the two large metropolitan areas. 32 out of 63 provinces were represented. The median number of sexual partners during the last six months was two. The sample composition stabilized well for 16 out of 17 variables. Conclusion: Results indicate that webRDS could be implemented at a low cost among Internet-using MSM in Vietnam. WebRDS may be a promising method for sampling of Internet-using MSM and other hidden groups.

  • 48.
    Berg, Lisa
    et al.
    Stockholm University, Faculty of Social Sciences, Department of Public Health Sciences. Stockholm University, Faculty of Social Sciences, The Swedish Institute for Social Research (SOFI).
    Brännström, Lars
    Stockholm University, Faculty of Social Sciences, Department of Social Work.
    Evicted children and subsequent placement in out-of-home care: A cohort study2018In: PLOS ONE, E-ISSN 1932-6203, Vol. 13, no 4, article id e0195295Article in journal (Refereed)
    Abstract [en]

    Background

    Evictions may have serious consequences for individuals’ health and wellbeing. Even though an eviction may be experienced as a significant crisis for the family, there is little previous knowledge on consequences for evicted children. This study represents the first attempt to examine to what extent children from evicted households were separated from their parents and placed in out-of-home care (foster family or residential care) using population-based data, net of observed confounding factors related to the socioeconomic and psychosocial circumstances of their parents.

    Methods

    This study takes advantage of information from a Swedish national database, consisting of about 8 000 evicted individuals and a random sample of 770 000 individuals from the national population, linked to individual-level, longitudinal data from Swedish national registers. Our analytical sample consists of information for more than 250 000 children born in 1995–2008, including 2 224 children from evicted households. We used binary logistic regression based on the Karlson/Holm/Breen method to account for observed imbalances at baseline between evicted and non-evicted children.

    Results

    Compared to non-evicted children, the crude odds ratio for placement in out-of-home care in evicted children was 12.10 (95% CI 8.54–17.14). Net of observed confounding factors related to the socioeconomic and psychosocial circumstances of the parents, evicted children had a twofold elevated risk of being placed in out-of-home care (odds ratio 2.26, 95% CI 1.55–3.27). Crude OR for evicted children in comparison with children under threat of eviction (eviction not formally executed) was 1.71 (95% CI 1.17–2.49) and adjusted OR 1.58 (95% CI 1.06–2.35).

    Conclusion

    Children who experience eviction constitute a disadvantaged group and are at significant risk of being separated from their parents and placed in out-of-home care. These results demonstrate the importance of providing support for these children and their parents. Strategies to prevent households with children from being evicted seem to be an important and viable intervention path.

  • 49.
    Bergström, Malin
    et al.
    Stockholm University, Faculty of Social Sciences, Department of Public Health Sciences, Centre for Health Equity Studies (CHESS). Karolinska Institutet, Sweden.
    Sarkadi, Anna
    Hjern, Anders
    Stockholm University, Faculty of Social Sciences, Department of Public Health Sciences, Centre for Health Equity Studies (CHESS). Karolinska Institutet, Sweden.
    Fransson, Emma
    Stockholm University, Faculty of Social Sciences, Department of Public Health Sciences, Centre for Health Equity Studies (CHESS).
    "We also communicate through a book in the diaper bag" - Separated parents' ways to coparent and promote adaptation of their 1-4 year olds in equal joint physical custody2019In: PLOS ONE, E-ISSN 1932-6203, Vol. 14, no 4, article id e0214913Article in journal (Refereed)
    Abstract [en]

    Joint physical custody (JPC) refers to a practice where children with separated parents share their time between the parents' respective homes. Studies on parents' views of JPC for young children are scarce. The aim of this interview study was to explore parents' perceptions on how they experience and practice equally shared JPC for their 1-4 year-olds in Sweden. Forty-six parents (18 fathers and 28 mothers) of 50 children (31 boys and 19 girls) under 5 years of age were interviewed. Parents were recruited through information in the media and represented a broad range of socioeconomic backgrounds, as well as both voluntary and court-ordered custody arrangements. The interviews were semi-structured and analyzed using systematic text condensation. Two themes emerged regarding the research question. In the first theme, Always free, never free, parents described their striving to coparent without a love relationship. While they appreciated the freedom of being a half-time parent, doing things one's own way, they felt constrained by the long-term commitment to live close to and keep discussing child rearing issues with the ex-partner. Good communication was key and lessened parent's feelings of being cut-off from half of the child's life. When JPC was ordered by court or conflicts were intense, parents tried to have less contact and worried when the children were in the other home. The second theme, Is it right, is it good?, included descriptions of how the parents monitored the child's responses to the living arrangement and made changes to optimize their adjustment. Adaptations included visits for the child with the other parent mid-week, shared meals or adapting schedules. In conclusion, these parents worked hard to make JPC work and cause minimal damage to their children. Most parents were pleased with the arrangements with the notable exception of couples experiencing ongoing conflict.

  • 50. Bermudez, Rafael
    et al.
    Feng, Yuanyuan
    Roleda, Michael Y.
    Tatters, Avery O.
    Hutchins, David A.
    Larsen, Thomas
    Boyd, Philip W.
    Hurd, Catriona L.
    Riebesell, Ulf
    Winder, Monika
    Stockholm University, Faculty of Science, Department of Ecology, Environment and Plant Sciences.
    Long-Term Conditioning to Elevated pCO(2) and Warming Influences the Fatty and Amino Acid Composition of the Diatom Cylindrotheca fusiformis2015In: PLOS ONE, E-ISSN 1932-6203, Vol. 10, no 5, article id e0123945Article in journal (Refereed)
    Abstract [en]

    The unabated rise in anthropogenic CO2 emissions is predicted to strongly influence the ocean's environment, increasing the mean sea-surface temperature by 4 degrees C and causing a pH decline of 0.3 units by the year 2100. These changes are likely to affect the nutritional value of marine food sources since temperature and CO2 can influence the fatty (FA) and amino acid (AA) composition of marine primary producers. Here, essential amino (EA) and polyunsaturated fatty (PUFA) acids are of particular importance due to their nutritional value to higher trophic levels. In order to determine the interactive effects of CO2 and temperature on the nutritional quality of a primary producer, we analyzed the relative PUFA and EA composition of the diatom Cylindrotheca fusiformis cultured under a factorial matrix of 2 temperatures (14 and 19 degrees C) and 3 partial pressures of CO2 (180, 380, 750 mu atm) for >250 generations. Our results show a decay of similar to 3% and similar to 6% in PUFA and EA content in algae kept at a pCO(2) of 750 mu atm (high) compared to the 380 mu atm (intermediate) CO2 treatments at 14 degrees C. Cultures kept at 19 degrees C displayed a similar to 3% lower PUFA content under high compared to intermediate pCO(2), while EA did not show differences between treatments. Algae grown at a pCO(2) of 180 mu atm (low) had a lower PUFA and AA content in relation to those at intermediate and high CO2 levels at 14 degrees C, but there were no differences in EA at 19 degrees C for any CO2 treatment. This study is the first to report adverse effects of warming and acidification on the EA of a primary producer, and corroborates previous observations of negative effects of these stressors on PUFA. Considering that only similar to 20% of essential biomolecules such as PUFA (and possibly EA) are incorporated into new biomass at the next trophic level, the potential impacts of adverse effects of ocean warming and acidification at the base of the food web may be amplified towards higher trophic levels, which rely on them as source of essential biomolecules.

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