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  • 201. Desamore, Aurelie
    et al.
    Patino, Jairo
    Mardulyn, Patrick
    Mcdaniel, Stuart F.
    Zanatta, Florian
    Laenen, Benjamin
    Stockholm University, Faculty of Science, Department of Ecology, Environment and Plant Sciences. Stockholm University, Science for Life Laboratory (SciLifeLab). University of Liège, Belgium.
    Vanderpoorten, Alain
    High migration rates shape the postglacial history of amphi-Atlantic bryophytes2016In: Molecular Ecology, ISSN 0962-1083, E-ISSN 1365-294X, Vol. 25, no 21, p. 5568-5584Article in journal (Refereed)
    Abstract [en]

    Paleontological evidence and current patterns of angiosperm species richness suggest that European biota experienced more severe bottlenecks than North American ones during the last glacial maximum. How well this pattern fits other plant species is less clear. Bryophytes offer a unique opportunity to contrast the impact of the last glacial maximum in North America and Europe because about 60% of the European bryoflora is shared with North America. Here, we use population genetic analyses based on approximate Bayesian computation on eight amphi-Atlantic species to test the hypothesis that North American populations were less impacted by the last glacial maximum, exhibiting higher levels of genetic diversity than European ones and ultimately serving as a refugium for the postglacial recolonization of Europe. In contrast with this hypothesis, the best-fit demographic model involved similar patterns of population size contractions, comparable levels of genetic diversity and balanced migration rates between European and North American populations. Our results thus suggest that bryophytes have experienced comparable demographic glacial histories on both sides of the Atlantic. Although a weak, but significant genetic structure was systematically recovered between European and North American populations, evidence for migration from and towards both continents suggests that amphi-Atlantic bryophyte population may function as a metapopulation network. Reconstructing the biogeographic history of either North American or European bryophyte populations therefore requires a large, trans-Atlantic geographic framework.

  • 202. Dessimoz, Christophe
    et al.
    Gabaldón, Toni
    Roos, David S.
    Sonnhammer, Erik L. L.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Herrero, Javier
    Toward community standards in the quest for orthologs2012In: Bioinformatics, ISSN 1367-4803, E-ISSN 1367-4811, Vol. 28, no 6, p. 900-904Article in journal (Other academic)
    Abstract [en]

    The identification of orthologs-genes pairs descended from a common ancestor through speciation, rather than duplication-has emerged as an essential component of many bioinformatics applications, ranging from the annotation of new genomes to experimental target prioritization. Yet, the development and application of orthology inference methods is hampered by the lack of consensus on source proteomes, file formats and benchmarks. The second 'Quest for Orthologs' meeting brought together stakeholders from various communities to address these challenges. We report on achievements and outcomes of this meeting, focusing on topics of particular relevance to the research community at large. The Quest for Orthologs consortium is an open community that welcomes contributions from all researchers interested in orthology research and applications.

  • 203. Desvignes, Thomas
    et al.
    Loher, Phillipe
    Eilbeck, Karen
    Ma, Jeffery
    Urgese, Gianvito
    Fromm, Bastian
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Sydes, Jason
    Aparicio-Puerta, Ernesto
    Barrera, Victor
    Espin, Roderic
    Thibord, Florian
    Bofill-De Ros, Xavier
    Londin, Eric
    Telonis, Aristeidis G.
    Ficarra, Elisa
    Friedländer, Marc R.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Postlethwait, John H.
    Rigoutsos, Isidore
    Hackenberg, Michael
    Vlachos, Ioannis S.
    Halushka, Marc K.
    Pantano, Lorena
    Unification of miRNA and isomiR research: the mirGFF3 format and the mirtop API2020In: Bioinformatics, ISSN 1367-4803, E-ISSN 1367-4811, Vol. 36, no 3, p. 698-703Article in journal (Refereed)
    Abstract [en]

    Motivation: MicroRNAs (miRNAs) are small RNA molecules (similar to 22 nucleotide long) involved in post-transcriptional gene regulation. Advances in high-throughput sequencing technologies led to the discovery of isomiRs, which are miRNA sequence variants. While many miRNA-seq analysis tools exist, the diversity of output formats hinders accurate comparisons between tools and precludes data sharing and the development of common downstream analysis methods. Results: To overcome this situation, we present here a community-based project, miRNA Transcriptomic Open Project (miRTOP) working towards the optimization of miRNA analyses. The aim of miRTOP is to promote the development of downstream isomiR analysis tools that are compatible with existing detection and quantification tools. Based on the existing GFF3 format, we first created a new standard format, mirGFF3, for the output of miRNA/isomiR detection and quantification results from small RNA-seq data. Additionally, we developed a command line Python tool, mirtop, to create and manage the mirGFF3 format. Currently, mirtop can convert into mirGFF3 the outputs of commonly used pipelines, such as seqbuster, isomiR-SEA, sRNAbench, Prost! as well as BAM files. Some tools have also incorporated the mirGFF3 format directly into their code, such as, miRge2.0, IsoMIRmap and OptimiR. Its open architecture enables any tool or pipeline to output or convert results into mirGFF3. Collectively, this isomiR categorization system, along with the accompanying mirGFF3 and mirtop API, provide a comprehensive solution for the standardization of miRNA and isomiR annotation, enabling data sharing, reporting, comparative analyses and benchmarking, while promoting the development of common miRNA methods focusing on downstream steps of miRNA detection, annotation and quantification.

  • 204. Dewapriya, Pradeep
    et al.
    Nilsson, Sandra
    Gorji, Sara Ghorbani
    O'Brien, Jake W.
    Bräunig, Jennifer
    Ramos, María José Gómez
    Donaldson, Eric
    Samanipour, Saer
    Martin, Jonathan W.
    Stockholm University, Faculty of Science, Department of Environmental Science. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Mueller, Jochen F.
    Kaserzon, Sarit L.
    Thomas, Kevin V.
    Novel Per- and Polyfluoroalkyl Substances Discovered in Cattle Exposed to AFFF-Impacted Groundwater2023In: Environmental Science and Technology, ISSN 0013-936X, E-ISSN 1520-5851, Vol. 57, no 36, p. 13635-13645Article in journal (Refereed)
    Abstract [en]

    The leaching of per- and polyfluoroalkyl substances (PFASs) from Australian firefighting training grounds has resulted in extensive contamination of groundwater and nearby farmlands. Humans, farm animals, and wildlife in these areas may have been exposed to complex mixtures of PFASs from aqueous film-forming foams (AFFFs). This study aimed to identify PFAS classes in pooled whole blood (n = 4) and serum (n = 4) from cattle exposed to AFFF-impacted groundwater and potentially discover new PFASs in blood. Thirty PFASs were identified at various levels of confidence (levels 1a–5a), including three novel compounds: (i) perfluorohexanesulfonamido 2-hydroxypropanoic acid (FHxSA-HOPrA), (ii) methyl((perfluorohexyl)sulfonyl)sulfuramidous acid, and (iii) methyl((perfluorooctyl)sulfonyl)sulfuramidous acid, belonging to two different classes. Biotransformation intermediate, perfluorohexanesulfonamido propanoic acid (FHxSA-PrA), hitherto unreported in biological samples, was detected in both whole blood and serum. Furthermore, perfluoroalkyl sulfonamides, including perfluoropropane sulfonamide (FPrSA), perfluorobutane sulfonamide (FBSA), and perfluorohexane sulfonamide (FHxSA) were predominantly detected in whole blood, suggesting that these accumulate in the cell fraction of blood. The suspect screening revealed several fluoroalkyl chain-substituted PFAS. The results suggest that targeting only the major PFASs in the plasma or serum of AFFF-exposed mammals likely underestimates the toxicological risks associated with exposure. Future studies of AFFF-exposed populations should include whole-blood analysis with high-resolution mass spectrometry to understand the true extent of PFAS exposure. 

  • 205. Dewey, Deborah
    et al.
    Martin, Jonathan W.
    Stockholm University, Faculty of Science, Department of Environmental Science. Stockholm University, Science for Life Laboratory (SciLifeLab).
    MacDonald, Amy M.
    Kinniburgh, David W.
    Letourneau, Nicole
    Giesbrecht, Gerald F.
    Field, Catherine J.
    Bell, Rhonda C.
    England-Mason, Gillian
    Sex-specific associations between maternal phthalate exposure and neurodevelopmental outcomes in children at 2 years of age in the APrON cohort2023In: Neurotoxicology, ISSN 0161-813X, E-ISSN 1872-9711, Vol. 98, p. 48-60Article in journal (Refereed)
    Abstract [en]

    Background: There is inconsistent evidence regarding the sex-specific associations between prenatal phthalate exposure and children's neurodevelopment. This could be due to differences in the phthalate exposures inves-tigated and the neurodevelopmental domains assessed.Objective: To evaluate the associations between prenatal phthalate exposure and sex-specific outcomes on measures of cognition, language, motor, executive function, and behaviour in children 2 years of age in the Alberta Pregnancy Outcomes and Nutrition (APrON) cohort.Methods: We evaluated the associations between prenatal phthalate exposure and sex-specific neuro-developmental outcomes in children at 2 years of age using data from 448 mothers and their children (222 girls, 226 boys). Nine phthalate metabolites were measured in maternal urine collected in the second trimester of pregnancy. Children's cognitive, language, and motor outcomes were assessed using the Bayley Scales of Infant Development - Third Edition (Bayley-III). Parents completed questionnaires on children's executive function and behavior, the Behavior Rating Inventory of Executive Function-Preschool Version (BRIEF-P) and Child Behavior Checklist (CBCL), respectively. Sex-stratified robust multivariate regressions were performed.Results: Higher maternal concentrations of & sigma;DEHP and its metabolites were associated with lower scores on the Bayley-III Cognitive (& beta;'s from-11.8 to-0.07 95% CI's from-21.3 to-0.01), Language (& beta;'s from-11.7 to-0. 09, 95% CI's from-22.3 to-0.02) and Motor (& beta;'s from-10.9 to-0.07, 95% CI from-20.4 to-0.01) composites in boys. The patterns of association in girls were in the opposite direction on the Cognitive and Language composites; on the Motor composite they were in the same direction as boys, but of reduced strength. Higher concentrations of & sigma;DEHP and its metabolites were associated with higher scores (i.e., more difficulties) on all measures of executive function in girls: inhibitory self-control (B's from 0.05 to 0.11, 95% CI s from-0.01 to 0.15), flexibility (B's from 0.04 to 0.11, 95% CI s from 0.01 to 0.21) and emergent metacognition (B's from-0.01 to 0.06, 95% CIs from-0.01 to 0.20). Similar patterns of attenuated associations were seen in boys. Higher concentrations of & sigma;DEHP and its metabolites were associated with more Externalizing Problems in girls and boys (B's from 0.03 to 6.82, 95% CIs from-0.08 to 12.0). Two phthalates, MMP and MBP, had sex-specific adverse associations on measures of executive function and behaviour, respectively, while MEP was positively associated with boys' cognitive, language, and motor performance. Limited associations were observed between mixtures of maternal phthalates and sex-specific neurodevelopmental outcomes.Conclusions: Maternal prenatal concentrations of DEHP phthalates were associated with sex specific difference on measures of cognition and language at 2 years of age, specifically, poorer outcomes in boys. Higher exposure to DEHP was associated with poorer motor, executive function, and behavioural outcomes in girls and boys but the strength of these associations differed by sex. Limited associations were noted between phthalate mixtures and child neurodevelopment.

  • 206. Di Palma, Francesco
    et al.
    Decherchi, Sergio
    Pardo-Avila, Fátima
    Succi, Sauro
    Levitt, Michael
    von Heijne, Gunnar
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Cavalli, Andrea
    Probing Interplays between Human XBP1u Translational Arrest Peptide and 80S Ribosome2022In: Journal of Chemical Theory and Computation, ISSN 1549-9618, E-ISSN 1549-9626, Vol. 18, no 3, p. 1905-1914Article in journal (Refereed)
    Abstract [en]

    The ribosome stalling mechanism is a crucial biological process, yet its atomistic underpinning is still elusive. In this framework, the human XBP1u translational arrest peptide (AP) plays a central role in regulating the unfolded protein response (UPR) in eukaryotic cells. Here, we report multimicrosecond all-atom molecular dynamics simulations designed to probe the interactions between the XBP1u AP and the mammalian ribosome exit tunnel, both for the wild type AP and for four mutant variants of different arrest potencies. Enhanced sampling simulations allow investigating the AP release process of the different variants, shedding light on this complex mechanism. The present outcomes are in qualitative/quantitative agreement with available experimental data. In conclusion, we provide an unprecedented atomistic picture of this biological process and clear-cut insights into the key AP-ribosome interactions.

  • 207. Dickerson, Aisha S.
    et al.
    Deng, Zhengyi
    Ransome, Yusuf
    Factor-Litvak, Pam
    Karlsson, Oskar
    Stockholm University, Science for Life Laboratory (SciLifeLab). Stockholm University, Faculty of Science, Department of Environmental Science and Analytical Chemistry.
    Associations of prenatal exposure to mixtures of organochlorine pesticides and smoking and drinking behaviors in adolescence2022In: Environmental Research, ISSN 0013-9351, E-ISSN 1096-0953, Vol. 206, article id 112431Article in journal (Refereed)
    Abstract [en]

    It is important to identify the factors that influence the prevalence of disinhibitory behaviors, as tobacco and alcohol use in adolescence is a strong predictor of continued use and substance abuse into adulthood. Organochlorine pesticides (OCPs) are persistent organic pollutants that pose a potential risk to the developing fetus and offspring long-term health. We examined associations between prenatal exposure OCPs and their metabolites (i. e., p,p'-DDT, p,p'-DDE, o,p'-DDT, oxychlordane, and hexachlombenzene (HCB)), both as a mixture and single compounds, and alcohol consumption and smoking at adolescence in a sample (n = 554) from the Child Health and Development Studies prospective birth cohort. Bayesian Kernel Machine Regression demonstrated a trend of higher risk of alcohol use and smoking with higher quartile mixture levels. Single-component analysis showed increased odds of smoking and drinking with increases in lipid-adjusted p,p'-DDE serum levels (aOR = 2.06, 95% CI 0.99-4.31, p = 0.05, per natural log unit increase). We found significant effect modification in these associations by sex with higher p,p '-DDT serum levels (aOR = 0.26, 95% CI 0.09-0.076, p = 0.01, per natural log unit increase) was associated with lower odds of smoking and drinking in female adolescents, while higher p,p'-DDE serum levels (aOR = 2.98, 95% CI 1.04-8.51, p = 0.04, per natural log unit increase) was associated with higher odds of the outcomes. Results of the mutually adjusted model were not significant for male adolescents. Further research to understand reasons for these sex-differences are warranted.

  • 208. Dickerson, Aisha S.
    et al.
    Ransome, Yusuf
    Karlsson, Oskar
    Stockholm University, Science for Life Laboratory (SciLifeLab). Stockholm University, Faculty of Science, Department of Environmental Science and Analytical Chemistry.
    Human prenatal exposure to polychlorinated biphenyls (PCBs) and risk behaviors in adolescence2019In: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 129, p. 247-255Article in journal (Refereed)
    Abstract [en]

    Polychlorinated biphenyls (PCBs) are chemicals used in a variety of products before they were widely banned due to toxic effects in humans and wildlife. Because of continued persistence and ubiquity of these contaminants, risk of exposure to people living in industrialized countries is still high. Experimental research show that developmental exposure to PCB may alter function of brain pleasure centers and potentially influence disinhibitory behaviors, including tobacco and alcohol use. Yet, the potential effects of developmental PCB exposure on adolescent substance use have not been studied in humans. We used the Child Health and Development Studies (CHDS), a prospective birth cohort study in the Oakland and East Bay areas of California, to investigate associations between prenatal exposure to PCB congeners (66, 74, 99, 118, 138, 153, 170, 180, 187, and 203) and later disinhibitory behaviors in adolescents, specifically alcohol consumption and smoking, in a randomly selected sample (n = 554). Total prenatal PCB exposure was not associated with disinhibitory behaviors, among adolescents. However, the adjusted odds ratio (aOR) for being a current smoker, was higher in subjects within the third quartile of maternal PCB 66 exposure compared to those below the median (aOR = 1.93; 95% CI 1.05, 3.55). The aOR for drinking > 2 alcoholic beverages per week, were also higher for adolescents within the third (aOR = 1.46; 95% CI 0.86, 2.47) and fourth quartile of PCB 66 exposure (aOR = 1.39; 95% CI 0.83, 2.35), but the differences did not reach statistical significance. These results suggest that this specific PCB congener may play a role inducing neurodevelopmental alterations that could potentially increase the risk of becoming a long-term user of tobacco and possibly alcohol. There were no notable differences between magnitude or direction of effect between boys and girls. Future replicate analyses with larger longitudinal samples and animal experimental studies of potential underlying mechanisms are warranted.

  • 209. Didion, John P.
    et al.
    Martin, Marcel
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Collins, Francis S.
    Atropos: specific, sensitive, and speedy trimming of sequencing reads2017In: PeerJ, E-ISSN 2167-8359, Vol. 5, article id e3720Article in journal (Refereed)
    Abstract [en]

    A key step in the transformation of raw sequencing reads into biological insights is the trimming of adapter sequences and low-quality bases. Read trimming has been shown to increase the quality and reliability while decreasing the computational requirements of downstream analyses. Many read trimming software tools are available; however, no tool simultaneously provides the accuracy, computational efficiency, and feature set required to handle the types and volumes of data generated in modern sequencing-based experiments. Here we introduce Atropos and show that it trims reads with high sensitivity and specificity while maintaining leadingedge speed. Compared to other state-of-the-art read trimming tools, Atropos achieves significant increases in trimming accuracy while remaining competitive in execution times. Furthermore, Atropos maintains high accuracy even when trimming data with elevated rates of sequencing errors. The accuracy, high performance, and broad feature set offered by Atropos makes it an appropriate choice for the pre-processing of Illumina, ABI SOLiD, and other current-generation short-read sequencing datasets. Atropos is open source and free software written in Python (3.3+) and available at https://github. com/jdidion/atropos.

  • 210. Dimou, Niki L.
    et al.
    Tsirigos, Konstantinos D.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab). Swedish e-Science Research Center, Sweden.
    Elofsson, Arne
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab). Swedish e-Science Research Center, Sweden.
    Bagos, Pantelis G.
    GWAR: robust analysis and meta-analysis of genome-wide association studies2017In: Bioinformatics, ISSN 1367-4803, E-ISSN 1367-4811, Vol. 33, no 10, p. 1521-1527Article in journal (Refereed)
    Abstract [en]

    Motivation: In the context of genome-wide association studies (GWAS), there is a variety of statistical techniques in order to conduct the analysis, but, in most cases, the underlying genetic model is usually unknown. Under these circumstances, the classical Cochran-Armitage trend test (CATT) is suboptimal. Robust procedures that maximize the power and preserve the nominal type I error rate are preferable. Moreover, performing a meta-analysis using robust procedures is of great interest and has never been addressed in the past. The primary goal of this work is to implement several robust methods for analysis and meta-analysis in the statistical package Stata and subsequently to make the software available to the scientific community. Results: The CATT under a recessive, additive and dominant model of inheritance as well as robust methods based on the Maximum Efficiency Robust Test statistic, the MAX statistic and the MIN2 were implemented in Stata. Concerning MAX and MIN2, we calculated their asymptotic null distributions relying on numerical integration resulting in a great gain in computational time without losing accuracy. All the aforementioned approaches were employed in a fixed or a random effects meta-analysis setting using summary data with weights equal to the reciprocal of the combined cases and controls. Overall, this is the first complete effort to implement procedures for analysis and meta-analysis in GWAS using Stata.

  • 211.
    Domingo-Prim, Judit
    et al.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Endara-Coll, Martin
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Bonath, Franziska
    Stockholm University, Science for Life Laboratory (SciLifeLab). Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Jimeno, Sonia
    Prados-Carvaja, Rosario
    Friedländer, Marc R.
    Stockholm University, Science for Life Laboratory (SciLifeLab). Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Huertas, Pablo
    Visa, Neus
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    EXOSC10 is required for RPA assembly and controlled DNA end resection at DNA double-strand breaks2019In: Nature Communications, E-ISSN 2041-1723, Vol. 10, article id 2135Article in journal (Refereed)
    Abstract [en]

    The exosome is a ribonucleolytic complex that plays important roles in RNA metabolism. Here we show that the exosome is necessary for the repair of DNA double-strand breaks (DSBs) in human cells and that RNA clearance is an essential step in homologous recombination. Transcription of DSB-flanking sequences results in the production of damage-induced long non-coding RNAs (dilncRNAs) that engage in DNA-RNA hybrid formation. Depletion of EXOSC10, an exosome catalytic subunit, leads to increased dilncRNA and DNA-RNA hybrid levels. Moreover, the targeting of the ssDNA-binding protein RPA to sites of DNA damage is impaired whereas DNA end resection is hyper-stimulated in EXOSC10-depleted cells. The DNA end resection deregulation is abolished by transcription inhibitors, and RNase H1 overexpression restores the RPA recruitment defect caused by EXOSC10 depletion, which suggests that RNA clearance of newly synthesized dilncRNAs is required for RPA recruitment, controlled DNA end resection and assembly of the homologous recombination machinery.

  • 212.
    Domingo-Prim, Judit
    et al.
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Endara-Coll, Martín
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Bonath, Franziska
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Jimeno, Sonia
    Friedländer, Marc
    Stockholm University, Science for Life Laboratory (SciLifeLab). Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Huertas, Pablo
    Visa, Neus
    Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    EXOSC10 is required for RPA assembly and controlled DNA resection at DNA dobule-strand breaksManuscript (preprint) (Other academic)
  • 213. Dong, Yang
    et al.
    Majda, Mateusz
    Šimura, Jan
    Horvath, Robert
    Stockholm University, Faculty of Science, Department of Ecology, Environment and Plant Sciences. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Srivastava, Anjil K.
    Łangowski, Łukasz
    Eldridge, Tilly
    Stacey, Nicola
    Slotte, Tanja
    Stockholm University, Faculty of Science, Department of Ecology, Environment and Plant Sciences.
    Sadanandom, Ari
    Ljung, Karin
    Smith, Richard S.
    Østergaard, Lars
    HEARTBREAK Controls Post-translational Modification of INDEHISCENT to Regulate Fruit Morphology in Capsella2020In: Current Biology, ISSN 0960-9822, E-ISSN 1879-0445, Vol. 30, no 19, p. 3880-3888Article in journal (Refereed)
    Abstract [en]

    Morphological variation is the basis of natural diversity and adaptation. For example, angiosperms (flowering plants) evolved during the Cretaceous period more than 100 mya and quickly colonized terrestrial habitats [1]. A major reason for their astonishing success was the formation of fruits, which exist in a myriad of different shapes and sizes [2]. Evolution of organ shape is fueled by variation in expression patterns of regulatory genes causing changes in anisotropic cell expansion and division patterns [3-5]. However, the molecular mechanisms that alter the polarity of growth to generate novel shapes are largely unknown. The heart-shaped fruits produced by members of the Capsella genus comprise an anatomical novelty, making it particularly well suited for studies on morphological diversification [6-8]. Here, we show that post-translational modification of regulatory proteins provides a critical step in organ-shape formation. Our data reveal that the SUMO protease, HEARTBREAK (HTB), from Capsella rubella controls the activity of the key regulator of fruit development, INDEHISCENT (CrIND in C. rubella), via de-SUMOylation. This post-translational modification initiates a transduction pathway required to ensure precisely localized auxin biosynthesis, thereby facilitating anisotropic cell expansion to ultimately form the heart-shaped Capsella fruit. Therefore, although variation in the expression of key regulatory genes is known to be a primary driver in morphological evolution, our work demonstrates how other processes-such as post-translational modification of one such regulator-affects organ morphology.

  • 214. Donolato, Marco
    et al.
    Antunes, Paula
    Bejhed, Rebecca S.
    Gómez de la Torre, Teresa Zardán
    Österberg, Frederik W.
    Strömberg, Mattias
    Nilsson, Mats
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Strømme, Maria
    Svedlindh, Peter
    Hansen, Mikkel F.
    Vavassori, Paolo
    Novel Readout Method for Molecular Diagnostic Assays Based on Optical Measurements of Magnetic Nanobead Dynamics2015In: Analytical Chemistry, ISSN 0003-2700, E-ISSN 1520-6882, Vol. 87, no 3, p. 1622-1629Article in journal (Refereed)
    Abstract [en]

    We demonstrate detection of DNA coils formed from a Vibrio cholerae DNA target at picomolar concentrations using a novel optomagnetic approach exploiting the dynamic behavior and optical anisotropy of magnetic nanobead (MNB) assemblies. We establish that the complex second harmonic optical transmission spectra of MNB suspensions measured upon application of a weak uniaxial AC magnetic field correlate well with the rotation dynamics of the individual MNBs. Adding a target analyte to the solution leads to the formation of permanent MNB clusters, namely, to the suppression of the dynamic MNB behavior. We prove that the optical transmission spectra are highly sensitive to the formation of permanent MNB clusters and, thereby to the target analyte concentration. As a specific clinically relevant diagnostic case, we detect DNA coils formed via padlock probe recognition and isothermal rolling circle amplification and benchmark against a commercial equipment. The results demonstrate the fast optomagnetic readout of rolling circle products from bacterial DNA utilizing the dynamic properties of MNBs in a miniaturized and low-cost platform requiring only a transparent window in the chip.

  • 215.
    Dou, Dan
    et al.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Hernández-Neuta, Iván
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Wang, Hao
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Östbye, Henrik
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Qian, Xiaoyan
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Thiele, Swantje
    Resa-Infante, Patricia
    Mounogou Kouassi, Nancy
    Sender, Vicky
    Hentrich, Karina
    Mellroth, Peter
    Henriques-Normark, Birgitta
    Gabriel, Gülsah
    Nilsson, Mats
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Daniels, Robert
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Analysis of IAV Replication and Co-infection Dynamics by a Versatile RNA Viral Genome Labeling Method2017In: Cell Reports, E-ISSN 2211-1247, Vol. 20, no 1, p. 251-263Article in journal (Refereed)
    Abstract [en]

    Genome delivery to the proper cellular compartment for transcription and replication is a primary goal of viruses. However, methods for analyzing viral genome localization and differentiating genomes with high identity are lacking, making it difficult to investigate entry-related processes and co-examine heterogeneous RNA viral populations. Here, we present an RNA labeling approach for single-cell analysis of RNA viral replication and co-infection dynamics in situ, which uses the versatility of padlock probes. We applied this method to identify influenza A virus (IAV) infections in cells and lung tissue with single-nucleotide specificity and to classify entry and replication stages by gene segment localization. Extending the classification strategy to co-infections of IAVs with single-nucleotide variations, we found that the dependence on intracellular trafficking places a time restriction on secondary co-infections necessary for genome reassortment. Altogether, these data demonstrate how RNA viral genome labeling can help dissect entry and co-infections.

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  • 216.
    Drew, David
    et al.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Boudker, Olga
    Ion and lipid orchestration of secondary active transport2024In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 626, no 8001, p. 963-974Article, review/survey (Refereed)
    Abstract [en]

    Transporting small molecules across cell membranes is an essential process in cell physiology. Many structurally diverse, secondary active transporters harness transmembrane electrochemical gradients of ions to power the uptake or efflux of nutrients, signalling molecules, drugs and other ions across cell membranes. Transporters reside in lipid bilayers on the interface between two aqueous compartments, where they are energized and regulated by symported, antiported and allosteric ions on both sides of the membrane and the membrane bilayer itself. Here we outline the mechanisms by which transporters couple ion and solute fluxes and discuss how structural and mechanistic variations enable them to meet specific physiological needs and adapt to environmental conditions. We then consider how general bilayer properties and specific lipid binding modulate transporter activity. Together, ion gradients and lipid properties ensure the effective transport, regulation and distribution of small molecules across cell membranes.

  • 217. Duart, Gerard
    et al.
    Lamb, John
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Ortiz-Mateu, Juan
    Elofsson, Arne
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Mingarro, Ismael
    Intra-Helical Salt Bridge Contribution to Membrane Protein Insertion2022In: Journal of Molecular Biology, ISSN 0022-2836, E-ISSN 1089-8638, Vol. 434, no 5, article id 167467Article in journal (Refereed)
    Abstract [en]

    Salt bridges between negatively (D, E) and positively charged (K, R, H) amino acids play an important role in protein stabilization. This has a more prevalent effect in membrane proteins where polar amino acids are exposed to a hydrophobic environment. In transmembrane (TM) helices the presence of charged residues can hinder the insertion of the helices into the membrane. It is possible that the formation of salt bridges could decrease the cost of membrane integration. However, the presence of intra-helical salt bridges in TM domains and their effect on insertion has not been properly studied yet. In this work, we show that potentially salt-bridge forming pairs are statistically over-represented in TM-helices. We then selected some candidates to experimentally determine the contribution of these electrostatic interactions to the translocon-assisted membrane insertion process. Using both in vitro and whole cell systems, we confirm the presence of intra-helical salt bridges in TM segments during biogenesis and determined that they contribute ~0.5 kcal/mol to the apparent free energy of membrane insertion (delta G(app)). Our observations suggest that salt bridge interactions can be stabilized during translocon-mediated insertion and thus could be relevant to consider for the future development of membrane protein prediction software. 

  • 218.
    Dussex, Nicolas
    et al.
    Stockholm University, Faculty of Science, Department of Zoology. Centre for Palaeogenetics, Sweden; Swedish Museum of Natural History, Sweden.
    Alberti, Federica
    Heino, Matti T.
    Olsen, Remi-André
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    van der Valk, Tom
    Ryman, Nils
    Stockholm University, Faculty of Science, Department of Zoology.
    Laikre, Linda
    Stockholm University, Faculty of Science, Department of Zoology.
    Ahlgren, Hans
    Stockholm University, Faculty of Humanities, Department of Archaeology and Classical Studies.
    Askeyev, Igor
    Askeyev, Oleg
    Shaymuratova, Dilyara N.
    Askeyev, Arthur O.
    Döppes, Doris
    Friedrich, Ronny
    Lindauer, Susanne
    Rosendahl, Wilfried
    Aspi, Jouni
    Hofreiter, Michael
    Lidén, Kerstin
    Stockholm University, Faculty of Humanities, Department of Archaeology and Classical Studies.
    Dalén, Love
    Díez-del-Molino, David
    Stockholm University, Faculty of Science, Department of Zoology. Centre for Palaeogenetics, Sweden; Swedish Museum of Natural History, Sweden.
    Moose genomes reveal past glacial demography and the origin of modern lineages2020In: BMC Genomics, E-ISSN 1471-2164, Vol. 21, no 1, article id 854Article in journal (Refereed)
    Abstract [en]

    Background: Numerous megafauna species from northern latitudes went extinct during the Pleistocene/Holocene transition as a result of climate-induced habitat changes. However, several ungulate species managed to successfully track their habitats during this period to eventually flourish and recolonise the holarctic regions. So far, the genomic impacts of these climate fluctuations on ungulates from high latitudes have been little explored. Here, we assemble a de-novo genome for the European moose (Alces alces) and analyse it together with re-sequenced nuclear genomes and ancient and modern mitogenomes from across the moose range in Eurasia and North America.

    Results: We found that moose demographic history was greatly influenced by glacial cycles, with demographic responses to the Pleistocene/Holocene transition similar to other temperate ungulates. Our results further support that modern moose lineages trace their origin back to populations that inhabited distinct glacial refugia during the Last Glacial Maximum (LGM). Finally, we found that present day moose in Europe and North America show low to moderate inbreeding levels resulting from post-glacial bottlenecks and founder effects, but no evidence for recent inbreeding resulting from human-induced population declines.

    Conclusions: Taken together, our results highlight the dynamic recent evolutionary history of the moose and provide an important resource for further genomic studies.

  • 219.
    Dussex, Nicolas
    et al.
    Stockholm University, Faculty of Science, Department of Zoology, Population Genetics. Centre for Palaeogenetics, Sweden; Swedish Museum of Natural History, Sweden; Norwegian University of Science and Technology, Sweden.
    Kurland, Sara
    Stockholm University, Faculty of Science, Department of Zoology, Population Genetics. Stockholm Univ, Dept Zool, Div Populat Genet, SE-10691 Stockholm, Sweden.
    Olsen, Remi-André
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Spong, Göran
    Ericsson, Göran
    Ekblom, Robert
    Ryman, Nils
    Stockholm University, Faculty of Science, Department of Zoology, Population Genetics.
    Dalén, Love
    Stockholm University, Faculty of Science, Department of Zoology, Population Genetics. Centre for Palaeogenetics, Sweden; Swedish Museum of Natural History, Sweden.
    Laikre, Linda
    Stockholm University, Faculty of Science, Department of Zoology, Population Genetics.
    Range-wide and temporal genomic analyses reveal the consequences of near-extinction in Swedish moose2023In: Communications Biology, E-ISSN 2399-3642, Vol. 6, no 1, article id 1035Article in journal (Refereed)
    Abstract [en]

    Ungulate species have experienced severe declines over the past centuries through overharvesting and habitat loss. Even if many game species have recovered thanks to strict hunting regulation, the genome-wide impacts of overharvesting are still unclear. Here, we examine the temporal and geographical differences in genome-wide diversity in moose (Alces alces) over its whole range in Sweden by sequencing 87 modern and historical genomes. We found limited impact of the 1900s near-extinction event but local variation in inbreeding and load in modern populations, as well as suggestion of a risk of future reduction in genetic diversity and gene flow. Furthermore, we found candidate genes for local adaptation, and rapid temporal allele frequency shifts involving coding genes since the 1980s, possibly due to selective harvesting. Our results highlight that genomic changes potentially impacting fitness can occur over short time scales and underline the need to track both deleterious and selectively advantageous genomic variation.

  • 220. Dziasek, Katarzyna
    et al.
    Simon, Lauriane
    Lafon-Placette, Clément
    Laenen, Benjamin
    Stockholm University, Faculty of Science, Department of Ecology, Environment and Plant Sciences. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Wärdig, Cecilia
    Santos-González, Juan
    Slotte, Tanja
    Stockholm University, Faculty of Science, Department of Ecology, Environment and Plant Sciences. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Köhler, Claudia
    Hybrid seed incompatibility in Capsella is connected to chromatin condensation defects in the endosperm2021In: PLOS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 17, no 2, article id e1009370Article in journal (Refereed)
    Abstract [en]

    Hybridization of closely related plant species is frequently connected to endosperm arrest and seed failure, for reasons that remain to be identified. In this study, we investigated the molecular events accompanying seed failure in hybrids of the closely related species pair Capsella rubella and C. grandiflora. Mapping of QTL for the underlying cause of hybrid incompatibility in Capsella identified three QTL that were close to pericentromeric regions. We investigated whether there are specific changes in heterochromatin associated with interspecific hybridizations and found a strong reduction of chromatin condensation in the endosperm, connected with a strong loss of CHG and CHH methylation and random loss of a single chromosome. Consistent with reduced DNA methylation in the hybrid endosperm, we found a disproportionate deregulation of genes located close to pericentromeric regions, suggesting that reduced DNA methylation allows access of transcription factors to targets located in heterochromatic regions. Since the identified QTL were also associated with pericentromeric regions, we propose that relaxation of heterochromatin in response to interspecies hybridization exposes and activates loci leading to hybrid seed failure.

  • 221.
    Díez, Beatriz
    et al.
    Stockholm University, Science for Life Laboratory (SciLifeLab). Stockholm University, Faculty of Science, Department of Ecology, Environment and Plant Sciences. Pontificia Universidad Católica de Chile, Chile; Center for Climate Change and Resilience Research (CR)2, Chile.
    Nylander, Johan A. A.
    Stockholm University, Science for Life Laboratory (SciLifeLab). Stockholm University, Faculty of Science, Department of Ecology, Environment and Plant Sciences. Swedish Museum of Natural History, Sweden.
    Ininbergs, Karolina
    Stockholm University, Science for Life Laboratory (SciLifeLab). Stockholm University, Faculty of Science, Department of Ecology, Environment and Plant Sciences.
    Dupont, Christopher L.
    Allen, Andrew E.
    Yooseph, Shibu
    Rusch, Douglas B.
    Bergman, Birgitta
    Stockholm University, Science for Life Laboratory (SciLifeLab). Stockholm University, Faculty of Science, Department of Ecology, Environment and Plant Sciences.
    Metagenomic Analysis of the Indian Ocean Picocyanobacterial Community: Structure, Potential Function and Evolution2016In: PLOS ONE, E-ISSN 1932-6203, Vol. 11, no 5, article id e0155757Article in journal (Refereed)
    Abstract [en]

    Unicellular cyanobacteria are ubiquitous photoautotrophic microbes that contribute substantially to global primary production. Picocyanobacteria such as Synechococcus and Prochlorococcus depend on chlorophyll a-binding protein complexes to capture light energy. In addition, Synechococcus has accessory pigments organized into phycobilisomes, and Prochlorococcus contains chlorophyll b. Across a surface water transect spanning the sparsely studied tropical Indian Ocean, we examined Synechococcus and Prochlorococcus occurrence, taxonomy and habitat preference in an evolutionary context. Shotgun sequencing of size fractionated microbial communities from 0.1 mu m to 20 mu m and subsequent phylogenetic analysis indicated that cyanobacteria account for up to 15% of annotated reads, with the genera Prochlorococcus and Synechococcus comprising 90% of the cyanobacterial reads, even in the largest size fraction (3.0-20 mm). Phylogenetic analyses of cyanobacterial lightharvesting genes (chl-binding pcb/isiA, allophycocyanin (apcAB), phycocyanin (cpcAB) and phycoerythin (cpeAB)) mostly identified picocyanobacteria clades comprised of overlapping sequences obtained from Indian Ocean, Atlantic and/or Pacific Oceans samples. Habitat reconstructions coupled with phylogenetic analysis of the Indian Ocean samples suggested that large Synechococcus-like ancestors in coastal waters expanded their ecological niche towards open oligotrophic waters in the Indian Ocean through lineage diversification and associated streamlining of genomes (e.g. loss of phycobilisomes and acquisition of Chl b); resulting in contemporary small celled Prochlorococcus. Comparative metagenomic analysis with picocyanobacteria populations in other oceans suggests that this evolutionary scenario may be globally important.

  • 222. Edelbroek, Bart
    et al.
    Kjellin, Jonas
    Biryukova, Inna
    Stockholm University, Science for Life Laboratory (SciLifeLab). Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Liao, Zhen
    Lundberg, Torgny
    Noegel, Angelika A.
    Eichinger, Ludwig
    Friedländer, Marc R.
    Stockholm University, Science for Life Laboratory (SciLifeLab). Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Söderbom, Fredrik
    Evolution of microRNAs in Amoebozoa and implications for the origin of multicellularity2024In: Nucleic Acids Research, ISSN 0305-1048, E-ISSN 1362-4962Article in journal (Refereed)
    Abstract [en]

    MicroRNAs (miRNAs) are important and ubiquitous regulators of gene expression in both plants and animals. They are thought to have evolved convergently in these lineages and hypothesized to have played a role in the evolution of multicellularity. In line with this hypothesis, miRNAs have so far only been described in few unicellular eukaryotes. Here, we investigate the presence and evolution of miRNAs in Amoebozoa, focusing on species belonging to AcanthamoebaPhysarum and dictyostelid taxonomic groups, representing a range of unicellular and multicellular lifestyles. miRNAs that adhere to both the stringent plant and animal miRNA criteria were identified in all examined amoebae, expanding the total number of protists harbouring miRNAs from 7 to 15. We found conserved miRNAs between closely related species, but the majority of species feature only unique miRNAs. This shows rapid gain and/or loss of miRNAs in Amoebozoa, further illustrated by a detailed comparison between two evolutionary closely related dictyostelids. Additionally, loss of miRNAs in the Dictyostelium discoideum drnB mutant did not seem to affect multicellular development and, hence, demonstrates that the presence of miRNAs does not appear to be a strict requirement for the transition from uni- to multicellular life.

  • 223. Edfeldt, Gabriella
    et al.
    Kaldhusdal, Vilde
    Czarnewski, Paulo
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Bradley, Frideborg
    Bergström, Sofia
    Lajoie, Julie
    Xu, Jiawu
    Månberg, Anna
    Kimani, Joshua
    Oyugi, Julius
    Nilsson, Peter
    Tjernlund, Annelie
    Fowke, Keith R.
    Kwon, Douglas S.
    Broliden, Kristina
    Distinct cervical tissue-adherent and luminal microbiome communities correlate with mucosal host gene expression and protein levels in Kenyan sex workers2023In: Microbiome, E-ISSN 2049-2618, Vol. 11, article id 67Article in journal (Refereed)
    Abstract [en]

    Background The majority of studies characterizing female genital tract microbiota have focused on luminal organisms, while the presence and impact of tissue-adherent ectocervical microbiota remain incompletely understood. Studies of luminal and tissue-associated bacteria in the gastrointestinal tract suggest that these communities may have distinct roles in health and disease. Here, we performed a multi-omics characterization of paired luminal and tissue samples collected from a cohort of Kenyan female sex workers.

    Results We identified a tissue-adherent bacterial microbiome, with a higher alpha diversity than the luminal microbiome, in which dominant genera overall included Gardnerella and Lactobacillus, followed by Prevotella, Atopobium, and Sneathia. About half of the L. iners-dominated luminal samples had a corresponding Gardnerella-dominated tissue microbiome. Broadly, the tissue-adherent microbiome was associated with fewer differentially expressed host genes than the luminal microbiome. Gene set enrichment analysis revealed that L. crispatus-dominated tissue-adherent communities were associated with protein translation and antimicrobial activity, whereas a highly diverse microbial community was associated with epithelial remodeling and pro-inflammatory pathways. Tissue-adherent communities dominated by L. iners and Gardnerella were associated with lower host transcriptional activity. Tissue-adherent microbiomes dominated by Lactobacillus and Gardnerella correlated with host protein profiles associated with epithelial barrier stability, although with a more pro-inflammatory profile for the Gardnerella-dominated microbiome group. Tissue samples with a highly diverse composition had a protein profile representing cell proliferation and pro-inflammatory activity.

    Conclusion We identified ectocervical tissue-adherent bacterial communities in all study participants of a female sex worker cohort. These communities were distinct from cervicovaginal luminal microbiota in a significant proportion of individuals. We further revealed that bacterial communities at both sites correlated with distinct host gene expression and protein levels. The tissue-adherent bacterial community could possibly act as a reservoir that seed the lumen with less optimal, non-Lactobacillus, bacteria.

  • 224. Einarsdottir, Elisabet
    et al.
    Svensson, Idor
    Darki, Fahimeh
    Peyrard-Janvid, Myriam
    Lindvall, Jessica M.
    Stockholm University, Science for Life Laboratory (SciLifeLab). Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Karolinska Institutet, Sweden.
    Ameur, Adam
    Jacobsson, Christer
    Klingberg, Torkel
    Kere, Juha
    Stockholm University, Science for Life Laboratory (SciLifeLab). Karolinska Institutet, Sweden; Folkhälsan Institute of Genetics, Finland; University of Helsinki, Finland.
    Matsson, Hans
    Mutation in CEP63 co-segregating with developmental dyslexia in a Swedish family2015In: Human Genetics, ISSN 0340-6717, E-ISSN 1432-1203, Vol. 134, no 11-12, p. 1239-1248Article in journal (Refereed)
    Abstract [en]

    Developmental dyslexia is the most common learning disorder in children. Problems in reading and writing are likely due to a complex interaction of genetic and environmental factors, resulting in reduced power of studies of the genetic factors underlying developmental dyslexia. Our approach in the current study was to perform exome sequencing of affected and unaffected individuals within an extended pedigree with a familial form of developmental dyslexia. We identified a two-base mutation, causing a p.R229L amino acid substitution in the centrosomal protein 63 kDa (CEP63), co-segregating with developmental dyslexia in this pedigree. This mutation is novel, and predicted to be highly damaging for the function of the protein. 3D modelling suggested a distinct conformational change caused by the mutation. CEP63 is localised to the centrosome in eukaryotic cells and is required for maintaining normal centriole duplication and control of cell cycle progression. We found that a common polymorphism in the CEP63 gene had a significant association with brain white matter volume. The brain regions were partly overlapping with the previously reported region influenced by polymorphisms in the dyslexia susceptibility genes DYX1C1 and KIAA0319. We hypothesise that CEP63 is particularly important for brain development and might control the proliferation and migration of cells when those two events need to be highly coordinated.

  • 225. Eisfeldt, Jesper
    et al.
    Pettersson, Maria
    Vezzi, Francesco
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Wincent, Josephine
    Käller, Max
    Gruselius, Joel
    Nilsson, Daniel
    Lundberg, Elisabeth Syk
    Carvalho, Claudia M. B.
    Lindstrand, Anna
    Comprehensive structural variation genome map of individuals carrying complex chromosomal rearrangements2019In: PLOS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 15, no 2, article id e1007858Article in journal (Refereed)
    Abstract [en]

    Complex chromosomal rearrangements (CCRs) are rearrangements involving more than two chromosomes or more than two breakpoints. Whole genome sequencing (WGS) allows for outstanding high resolution characterization on the nucleotide level in unique sequences of such rearrangements, but problems remain for mapping breakpoints in repetitive regions of the genome, which are known to be prone to rearrangements. Hence, multiple complementary WGS experiments are sometimes needed to solve the structures of CCRs. We have studied three individuals with CCRs: Case 1 and Case 2 presented with de novo karyotypically balanced, complex interchromosomal rearrangements (46,XX,t(2;8;15)(q35;q24.1;q22) and 46,XY,t(1;10;5)(q32;p12;q31)), and Case 3 presented with a de novo, extremely complex intrachromosomal rearrangement on chromosome 1. Molecular cytogenetic investigation revealed cryptic deletions in the breakpoints of chromosome 2 and 8 in Case 1, and on chromosome 10 in Case 2, explaining their clinical symptoms. In Case 3, 26 breakpoints were identified using WGS, disrupting five known disease genes. All rearrangements were subsequently analyzed using optical maps, linked-read WGS, and short-read WGS. In conclusion, we present a case series of three unique de novo CCRs where we by combining the results from the different technologies fully solved the structure of each rearrangement. The power in combining short-read WGS with long-molecule sequencing or optical mapping in these unique de novo CCRs in a clinical setting is demonstrated. Author summary Unexpected complexities are common findings in the breakpoints of karyotypically balanced complex chromosomal rearrangements (CCRs). Such findings are of clinical importance, as they may be the cause of mendelian phenotypes in the rearrangement carrier. Whole genome sequencing (WGS) allows for high resolution characterization of CCRs, but problems remain for mapping breakpoints located in repetitive regions of the genome, which are known to be prone to rearrangements. In our study, we use multiple complementary WGS experiments to solve the structures of three CCRs originally identified by karyotyping. In all cases, the genomic structure of the derivative chromosomes was resolved and a molecular genetic explanation of the clinical symptoms of the patients was obtained. Furthermore, we compare the performance, sensitivity and resolution of four different WGS techniques for solving these CCRs in a clinical diagnostic laboratory set.

  • 226. Ekim, Baris
    et al.
    Sahlin, Kristoffer
    Stockholm University, Faculty of Science, Department of Mathematics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Medvedev, Paul
    Berger, Bonnie
    Chikhi, Rayan
    Efficient mapping of accurate long reads in minimizer space with mapquik2023In: Genome Research, ISSN 1088-9051, E-ISSN 1549-5469, Vol. 33, no 7, p. 1188-1197Article in journal (Refereed)
    Abstract [en]

    DNA sequencing data continue to progress toward longer reads with increasingly lower sequencing error rates. We focus on the critical problem of mapping, or aligning, low-divergence sequences from long reads (e.g., Pacific Biosciences [PacBio] HiFi) to a reference genome, which poses challenges in terms of accuracy and computational resources when using cutting-edge read mapping approaches that are designed for all types of alignments. A natural idea would be to optimize efficiency with longer seeds to reduce the probability of extraneous matches; however, contiguous exact seeds quickly reach a sensitivity limit. We introduce mapquik, a novel strategy that creates accurate longer seeds by anchoring alignments through matches of k consecutively sampled minimizers (k-min-mers) and only indexing k-min-mers that occur once in the reference genome, thereby unlocking ultrafast mapping while retaining high sensitivity. We show that mapquik significantly accelerates the seeding and chaining steps-fundamental bottlenecks to read mapping-for both the human and maize genomes with >96% sensitivity and near-perfect specificity. On the human genome, for both real and simulated reads, mapquik achieves a 37x speedup over the state-of-the-art tool minimap2, and on the maize genome, mapquik achieves a 410x speedup over minimap2, making mapquik the fastest mapper to date. These accelerations are enabled from not only minimizer-space seeding but also a novel heuristic O(n) pseudochaining algorithm, which improves upon the long-standing O(nlogn) bound. Minimizer-space computation builds the foundation for achieving real-time analysis of long-read sequencing data.

  • 227.
    Elfageih, Rageia
    et al.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Karyolaimos, Alexandros
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Kemp, Grant
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    de Gier, Jan-Willem
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    von Heijne, Gunnar
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Kudva, Renuka
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics.
    Cotranslational folding of alkaline phosphatase in the periplasm of Escherichia coli2020In: Protein Science, ISSN 0961-8368, E-ISSN 1469-896X, Vol. 29, no 10, p. 2028-2037Article in journal (Refereed)
    Abstract [en]

    Cotranslational protein folding studies using Force Profile Analysis, a method where the SecM translational arrest peptide is used to detect folding-induced forces acting on the nascent polypeptide, have so far been limited mainly to small domains of cytosolic proteins that fold in close proximity to the translating ribosome. In this study, we investigate the cotranslational folding of the periplasmic, disulfide bond-containing Escherichia coli protein alkaline phosphatase (PhoA) in a wild-type strain background and a strain background devoid of the periplasmic thiol: disulfide interchange protein DsbA. We find that folding-induced forces can be transmitted via the nascent chain from the periplasm to the polypeptide transferase center in the ribosome, a distance of similar to 160 angstrom, and that PhoA appears to fold cotranslationally via at least two disulfide-stabilized folding intermediates. Thus, Force Profile Analysis can be used to study cotranslational folding of proteins in an extra-cytosolic compartment, like the periplasm.

  • 228. El-Gebali, Sara
    et al.
    Mistry, Jaina
    Bateman, Alex
    Eddy, Sean R.
    Luciani, Aurelien
    Potter, Simon C.
    Qureshi, Matloob
    Richardson, Lorna J.
    Salazar, Gustavo A.
    Smart, Alfredo
    Sonnhammer, Erik L. L.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Hirsh, Layla
    Paladin, Lisanna
    Piovesan, Damiano
    Tosatto, Silvio C. E.
    Finn, Robert D.
    The Pfam protein families database in 20192019In: Nucleic Acids Research, ISSN 0305-1048, E-ISSN 1362-4962, Vol. 47, no D1, p. D427-D432Article in journal (Refereed)
    Abstract [en]

    The last few years have witnessed significant changes in Pfam (https://pfam.xfam.org). The number of families has grown substantially to a total of 17,929 in release 32.0. New additions have been coupled with efforts to improve existing families, including refinement of domain boundaries, their classification into Pfam clans, as well as their functional annotation. We recently began to collaborate with the RepeatsDB resource to improve the definition of tandem repeat families within Pfam. We carried out a significant comparison to the structural classification database, namely the Evolutionary Classification of Protein Domains (ECOD) that led to the creation of 825 new families based on their set of uncharacterized families(EUFs). Furthermore, we also connected Pfam entries to the Sequence Ontology (SO) through mapping of the Pfam type definitions to SO terms. Since Pfam has many community contributors, we recently enabled the linking between authorship of all Pfam entries with the corresponding authors' ORCID identifiers. This effectively permits authors to claim credit for their Pfam curation and link them to their ORCID record.

  • 229. El-Heliebi, Amin
    et al.
    Hille, Claudia
    Laxman, Navya
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Svedlund, Jessica
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Haudum, Christoph
    Ercan, Erkan
    Kroneis, Thomas
    Chen, Shukun
    Smolle, Maria
    Rossmann, Christopher
    Krzywkowski, Tomasz
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Ahlford, Annika
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab). Devyser AB, Sweden.
    Darai, Evangelia
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    von Amsberg, Gunhild
    Alsdorf, Winfried
    König, Frank
    Löhr, Matthias
    de Kruijff, Inge
    Riethdorf, Sabine
    Gorges, Tobias M.
    Pantel, Klaus
    Bauernhofer, Thomas
    Nilsson, Mats
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Sedlmayr, Peter
    In Situ Detection and Quantification of AR-V7, AR-FL, PSA, and KRAS Point Mutations in Circulating Tumor Cells2018In: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 64, no 3, p. 536-546Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Liquid biopsies can be used in castration-resistant prostate cancer (CRPC) to detect androgen receptor splice variant 7 (AR-V7), a splicing product of the androgen receptor. Patients with AR-V7-positive circulating tumor cells (CTCs) have greater benefit of taxane chemotherapy compared with novel hormonal therapies, indicating a treatment-selection biomarker. Likewise, in those with pancreatic cancer (PaCa), KRAS mutations act as prognostic biomarkers. Thus, there is an urgent need for technology investigating the expression and mutation status of CTCs. Here, we report an approach that adds AR-V7 or KRAS status to CTC enumeration, compatible with multiple CTC-isolation platforms.

    METHODS: We studied 3 independent CTC-isolation devices (CellCollector, Parsortix, CellSearch) for the evaluation of AR-V7 or KRAS status of CTCs with in situ padlock probe technology. Padlock probes allow highly specific detection and visualization of transcripts on a cellular level. We applied padlock probes for detecting AR-V7, androgen receptor full length (AR-FL), and prostate-specific antigen (PSA) in CRPC and KRAS wildtype (wt) and mutant (mut) transcripts in PaCa in CTCs from 46 patients.

    RESULTS: In situ analysis showed that 71% (22 of 31) of CRPC patients had detectable AR-V7 expression ranging from low to high expression [1-76 rolling circle products (RCPs)/CTC]. In PaCa patients, 40% (6 of 15) had KRAS mut expressing CTCs with 1 to 8 RCPs/CTC. In situ padlock probe analysis revealed CTCs with no detectable cytokeratin expression but positivity for AR-V7 or KRAS mut transcripts.

    CONCLUSIONS: Padlock probe technology enables quantification of AR-V7, AR-FL, PSA, and KRAS mut/wt transcripts in CTCs. The technology is easily applicable in routine laboratories and compatible with multiple CTC-isolation devices.

  • 230.
    Elihn, Karine
    et al.
    Stockholm University, Faculty of Science, Department of Environmental Science.
    Dalmijn, Joost
    Stockholm University, Faculty of Science, Department of Environmental Science.
    Froment, Jean
    Stockholm University, Faculty of Science, Department of Environmental Science.
    Haland, Alexander
    Johansson, Jana
    Stockholm University, Faculty of Science, Department of Environmental Science.
    Karlsson, Hanna L.
    Martin, Jonathan W.
    Stockholm University, Faculty of Science, Department of Environmental Science. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Mikoviny, Tomas
    Norman, Michael
    Piel, Felix
    Sadiktsis, Ioannis
    Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK). Stockholm University, Faculty of Science, Department of Environmental Science. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Schlesinger, Daniel
    Silvergren, Sanna
    Vallabani, N. V. Srikanth
    Wisthaler, Armin
    Steimer, Sarah
    Stockholm University, Faculty of Science, Department of Environmental Science.
    Air quality impacts of a large waste fire in Stockholm, Sweden2023In: Atmospheric Environment, ISSN 1352-2310, E-ISSN 1873-2844, Vol. 315, article id 120124Article in journal (Refereed)
    Abstract [en]

    Fires in waste facilities are a common occurrence. Since many waste facilities are located adjacent to densely populated areas, these fires could potentially expose large populations to the emitted pollutants. However, at the moment there are only few field studies investigating the impact of waste fire emissions on air quality since the unpredictable nature of these events makes them challenging to capture. This study investigated the impact of a large and persistent un-prescribed fire in a waste storage facility in Stockholm county, Sweden, on the local air quality of two residential areas in close proximity to the fire. In-situ measurements of particulate matter, black carbon and nitrogen oxide concentrations were conducted both during open burning and after the fire was fully covered. In addition, filter samples were collected for offline analysis of organic composition, metal content and toxicity. Strongly increased concentrations of PM10, PM2.5 and black carbon were found during the open burning period, especially when the wind was coming from the direction of the fire. In addition, elevated concentrations of particulate heavy metals and polycyclic aromatic hydrocarbons were observed in the air during the open burning period. These results show that waste fires can have a strong impact on the air quality of nearby residential areas.

  • 231. El-Morsy, E. M.
    et al.
    Hassan, H. M.
    Ahmed, Engy
    Stockholm University, Faculty of Science, Department of Geological Sciences. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Biodegradative activities of fungal isolates from plastic contaminated soils2017In: Mycosphere, ISSN 2077-7000, E-ISSN 2077-7019, Vol. 8, no 8, p. 1071-1087Article in journal (Refereed)
    Abstract [en]

    Fungal strains were isolated from plastic contaminated soils in open dump sites located in different governorates in Egypt. The isolates showed various abilities in enzymes production that were related to soil origins and characteristics. For example, fungi isolated from El-Sharqia soil were able to produce protease, esterase, lipase followed by those isolated from Ismailia soil. Moreover, isolates with high esterase activity were identified as Monascus ruber, Monascus sanguineus and Monascus sp. The results showed that M. ruber could produce maximum esterase concentration followed by M. sanguineus. The same three Monascus species were selected to assess polyurethane biodegradation. Monascus sp. isolated from El-Sharqia was the most efficient isolate in degradation of polyurethane in the form of Impranil DLN. In addition, SEM micrographs and zeta potential measurements confirmed the adsorption and complex formation between the polyurethane and the hyphae of Monascus sp.

  • 232.
    Elofsson, Arne
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Progress at protein structure prediction, as seen in CASP152023In: Current opinion in structural biology, ISSN 0959-440X, E-ISSN 1879-033X, Vol. 80, article id 102594Article, review/survey (Refereed)
    Abstract [en]

    In Dec 2020, the results of AlphaFold version 2 were presented at CASP14, sparking a revolution in the field of protein structure predictions. For the first time, a purely computational method could challenge experimental accuracy for structure prediction of single protein domains. The code of AlphaFold v2 was released in the summer of 2021, and since then, it has been shown that it can be used to accurately predict the structure of most ordered proteins and many protein–protein interactions. It has also sparked an explosion of development in the field, improving AI-based methods to predict protein complexes, disordered regions, and protein design. Here I will review some of the inventions sparked by the release of AlphaFold.

  • 233.
    Elofsson, Arne
    et al.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Han, Ling
    Bianchi, Enrica
    Wright, Gavin J.
    Jovine, Luca
    Deep learning insights into the architecture of the mammalian egg-sperm fusion synapse2024In: eLIFE, E-ISSN 2050-084X, Vol. 13, article id RP93131Article in journal (Refereed)
    Abstract [en]

    A crucial event in sexual reproduction is when haploid sperm and egg fuse to form a new diploid organism at fertilization. In mammals, direct interaction between egg JUNO and sperm IZUMO1 mediates gamete membrane adhesion, yet their role in fusion remains enigmatic. We used AlphaFold to predict the structure of other extracellular proteins essential for fertilization to determine if they could form a complex that may mediate fusion. We first identified TMEM81, whose gene is expressed by mouse and human spermatids, as a protein having structural homologies with both IZUMO1 and another sperm molecule essential for gamete fusion, SPACA6. Using a set of proteins known to be important for fertilization and TMEM81, we then systematically searched for predicted binary interactions using an unguided approach and identified a pentameric complex involving sperm IZUMO1, SPACA6, TMEM81 and egg JUNO, CD9. This complex is structurally consistent with both the expected topology on opposing gamete membranes and the location of predicted N-glycans not modeled by AlphaFold-Multimer, suggesting that its components could organize into a synapse-like assembly at the point of fusion. Finally, the structural modeling approach described here could be more generally useful to gain insights into transient protein complexes difficult to detect experimentally.

  • 234.
    Elofsson, Arne
    et al.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Joo, Keehyoung
    Keasar, Chen
    Lee, Jooyoung
    Maghrabi, Ali H. A.
    Manavalan, Balachandran
    McGuffin, Liam J.
    Menéndez Hurtado, David
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Mirabello, Claudio
    Pilstål, Robert
    Sidi, Tomer
    Uziela, Karolis
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Wallner, Björn
    Methods for estimation of model accuracy in CASP122018In: Proteins: Structure, Function, and Bioinformatics, ISSN 0887-3585, E-ISSN 1097-0134, Vol. 86, no S1, p. 361-373Article in journal (Refereed)
    Abstract [en]

    Methods to reliably estimate the quality of 3D models of proteins are essential drivers for the wide adoption and serious acceptance of protein structure predictions by life scientists. In this article, the most successful groups in CASP12 describe their latest methods for estimates of model accuracy (EMA). We show that pure single model accuracy estimation methods have shown clear progress since CASP11; the 3 top methods (MESHI, ProQ3, SVMQA) all perform better than the top method of CASP11 (ProQ2). Although the pure single model accuracy estimation methods outperform quasi-single (ModFOLD6 variations) and consensus methods (Pcons, ModFOLDclust2, Pcomb-domain, and Wallner) in model selection, they are still not as good as those methods in absolute model quality estimation and predictions of local quality. Finally, we show that when using contact-based model quality measures (CAD, lDDT) the single model quality methods perform relatively better.

  • 235.
    Elvers, Ingegerd
    et al.
    Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
    Hagenkort, Anna
    Stockholm University, Science for Life Laboratory (SciLifeLab).
    Johansson, Fredrik
    Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
    Djureinovic, Tatjana
    Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
    Lagerqvist, Anne
    Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
    Schultz, Niklas
    Stockholm University, Science for Life Laboratory (SciLifeLab).
    Stoimenov, Ivaylo
    Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
    Erixon, Klaus
    Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
    Helleday, Thomas
    Stockholm University, Science for Life Laboratory (SciLifeLab).
    CHK1 activity is required for continuous replication fork elongation but not stabilization of post-replicative gaps after UV irradiation2012In: Nucleic Acids Research, ISSN 0305-1048, E-ISSN 1362-4962, Vol. 40, no 17, p. 8440-8448Article in journal (Refereed)
    Abstract [en]

    Ultraviolet (UV)-induced DNA damage causes an efficient block of elongating replication forks. The checkpoint kinase, CHK1 has been shown to stabilize replication forks following hydroxyurea treatment. Therefore, we wanted to test if the increased UV sensitivity caused by the unspecific kinase inhibitor caffeine-inhibiting ATM and ATR amongst other kinases-is explained by inability to activate the CHK1 kinase to stabilize replicative structures. For this, we used cells deficient in polymerase eta (Pol eta), a translesion synthesis polymerase capable of properly bypassing the UV-induced cis-syn TT pyrimidine dimer, which blocks replication. These cells accumulate gaps behind progressing replication forks after UV exposure. We demonstrate that both caffeine and CHK1 inhibition, equally retards continuous replication fork elongation after UV treatment. Interestingly, we found more pronounced UV-sensitization by caffeine than with the CHK1 inhibitor in clonogenic survival experiments. Furthermore, we demonstrate an increased collapse of replicative structures after caffeine treatment, but not after CHK1 inhibition, in UV-irradiated cells. This demonstrates that CHK1 activity is not required for stabilization of gaps induced during replication of UV-damaged DNA. These data suggest that elongation and stabilization of replicative structures at UV-induced DNA damage are distinct mechanisms, and that CHK1 is only involved in replication elongation.

  • 236. Emanuelsson, Olof
    et al.
    Arvestad, Lars
    Stockholm University, Faculty of Science, Numerical Analysis and Computer Science (NADA). Stockholm University, Science for Life Laboratory (SciLifeLab). Swedish e-Science Research Center, Sweden.
    Käll, Lukas
    Engagera och aktivera studenter med inspiration från konferenser: examination genom poster-presentation2014In: Proceedings 2014: 8:e Pedagogiska inspirationskonferensen 17 december 2014, Lund: Lund University , 2014Conference paper (Refereed)
    Abstract [sv]

    I en forskningsnära kurs om 7.5 hp på master-nivå inom bioinformatikämnet vid KTH består drygt halva kursen av ett projekt som genomförs i grupper om tre studenter. Varje projekt har en egen projektuppgift med inget eller marginellt överlapp med andra gruppers uppgifter. Projekten är så gott som uteslutande baserade på aktuella frågeställningar i lärarteamets egna forskningsgrupper eller deras närhet. Projektet redovisas dels genom en posterpresentation, dels med individuell webbaserad projektdagbok. Vid posterredovisningen, som omfattar tre timmar i slutet av tentamensperioden, är alla kursdeltagare med. Vi försöker i möjligaste mån efterlikna situationen där ett autentiskt forskningsresultat presenteras på en riktig konferens. Varje deltagare (student) förväntas alltså ta del av varje annan grupps poster, på samma sätt som sker vid de flesta vetenskapliga konferenser. Vi genomför en enklare kamratbedömning på posternivå, där varje student ska avge en kort och konfidentiell kommentar om var och en av övriga postrar. Kursens lärare bedömer förstås också postrarna. En av svårigheterna är att sätta individuella betyg. Här använder vi oss av individuella projektdagböcker, som ger vägledning till de olika individernas insatser inom projektet. Vi har provat detta under fyra kursomgångar med som mest sju projekt. Examinationsformen är rolig och motiverande både för studenterna och lärarna.

  • 237. Engelbrecht, Leon de Villiers
    et al.
    Ji, Xiaoyan
    Carbonaro, Carlo Maria
    Laaksonen, Aatto
    Stockholm University, Science for Life Laboratory (SciLifeLab). Stockholm University, Faculty of Science, Department of Materials and Environmental Chemistry (MMK), Physical Chemistry. University of Cagliari, Cagliari, Italy; Luleå University of Technology, Luleå, Sweden; “Petru Poni” Institute of Macromolecular Chemistry, Iasi, Romania; Nanjing Tech University, Nanjing, China.
    Mocci, Francesca
    MD simulations explain the excess molar enthalpies in pseudo-binary mixtures of a choline chloride-based deep eutectic solvent with water or methanol2022In: Frontiers in Chemistry, E-ISSN 2296-2646, Vol. 10, article id 983281Article in journal (Refereed)
    Abstract [en]

    The addition of molecular liquid cosolvents to choline chloride (ChCl)-based deep eutectic solvents (DESs) is increasingly investigated for reducing the inherently high bulk viscosities of the latter, which represent a major obstacle for potential industrial applications. The molar enthalpy of mixing, often referred to as excess molar enthalpy HE-a property reflecting changes in intermolecular interactions upon mixing-of the well-known ChCl/ethylene glycol (1:2 molar ratio) DES mixed with either water or methanol was recently found to be of opposite sign at 308.15 K: Mixing of the DES with water is strongly exothermic, while methanol mixtures are endothermic over the entire mixture composition range. Knowledge of molecular-level liquid structural changes in the DES following cosolvent addition is expected to be important when selecting such pseudo-binary mixtures for specific applications, e.g., solvents. With the aim of understanding the reason for the different behavior of selected DES/water or methanol mixtures, we performed classical MD computer simulations to study the changes in intermolecular interactions thought to be responsible for the observed HE sign difference. Excess molar enthalpies computed from our simulations reproduce, for the first time, the experimental sign difference and composition dependence of the property. We performed a structural analysis of simulation configurations, revealing an intriguing difference in the interaction modes of the two cosolvents with the DES chloride anion: water molecules insert between neighboring chloride anions, forming ionic hydrogen-bonded bridges that draw the anions closer, whereas dilution of the DES with methanol results in increased interionic separation. Moreover, the simulated DES/water mixtures were found to contain extended hydrogen-bonded structures containing water-bridged chloride pair arrangements, the presence of which may have important implications for solvent applications.

  • 238. England-Mason, Gillian
    et al.
    Grohs, Melody N.
    Reynolds, Jess E.
    MacDonald, Amy
    Kinniburgh, David
    Liu, Jiaying
    Martin, Jonathan W.
    Stockholm University, Faculty of Science, Department of Environmental Science and Analytical Chemistry. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Lebel, Catherine
    Dewey, Deborah
    White matter microstructure mediates the association between prenatal exposure to phthalates and behavior problems in preschool children2020In: Environmental Research, ISSN 0013-9351, E-ISSN 1096-0953, Vol. 182, article id 109093Article in journal (Refereed)
    Abstract [en]

    Background: Previous research reports associations between prenatal exposure to phthalates and childhood behavior problems; however, the neural mechanisms that may underlie these associations are relatively unexplored. Objective: This study examined microstructural white matter as a possible mediator of the associations between prenatal phthalate exposure and behavior problems in preschool-aged children. Methods: Data are from a subsample of a prospective pregnancy cohort, the Alberta Pregnancy Outcomes and Nutrition (APrON) study (n = 76). Mother-child pairs were included if mothers provided a second trimester urine sample, if the child completed a successful magnetic resonance imaging (MRI) scan at age 3-5 years, and if the Child Behavior Checklist was completed within 6 months of the MRI scan. Molar sums of high (HMWP) and low molecular weight phthalates (LMWP) were calculated from levels in urine samples. Associations between prenatal phthalate concentrations, fractional anisotropy (FA) and mean diffusivity (MD) in 10 major white matter tracts, and preschool behavior problems were investigated. Results: Maternal prenatal phthalate concentrations were associated with MD of the right inferior fronto-occipital fasciculus (IFO), right pyramidal fibers, left and right uncinate fasciculus (UF), and FA of the left inferior longitudinal fasciculus (ILF). Mediation analyses showed that prenatal exposure to HMWP was indirectly associated with Internalizing (path ab = 0.09, CI.95 = 0.02, 0.20) and Externalizing Problems (path ab = 0.09, CI.95 = 0.01, 0.19) through MD of the right IFO, and to Internalizing Problems (path ab = 0.11, CI.95 = 0.01, 0.23) through MD of the right pyramidal fibers. Discussion: This study provides the first evidence of childhood neural correlates of prenatal phthalate exposure. Results suggest that prenatal phthalate exposure may be related to microstructural white matter in the IFO, pyramidal fibers, UF, and ILF. Further, MD of the right IFO and pyramidal fibers may transmit childhood risk for behavioral problems.

  • 239. England-Mason, Gillian
    et al.
    Liu, Jiaying
    Martin, Jonathan W.
    Stockholm University, Faculty of Science, Department of Environmental Science and Analytical Chemistry. Stockholm University, Science for Life Laboratory (SciLifeLab). University of Alberta, Canada.
    Giesbrecht, Gerald F.
    Letourneau, Nicole
    Dewey, Deborah
    Postnatal BPA is associated with increasing executive function difficulties in preschool children2021In: Pediatric Research, ISSN 0031-3998, E-ISSN 1530-0447, Vol. 89, p. 686-693Article in journal (Refereed)
    Abstract [en]

    Background Early bisphenol exposure may have consequences for executive function development, but less is known about potential sex effects. We hypothesized that early bisphenol A (BPA) and bisphenol S (BPS) exposures would be associated with sex-dependent changes in preschool executive function. Methods A subsample of the Alberta Pregnancy Outcomes and Nutrition (APrON) cohort (n = 312) provided maternal second trimester (prenatal) and 3-month postpartum (postnatal) urine samples, from which BPA and BPS concentrations were quantified. When children were age 2 and 4, mothers completed the Behavior Rating Inventory of Executive Function-Preschool Version (BRIEF-P). Changes in standardized T scores on the BRIEF-P indexes of inhibitory self-control, flexibility, and emergent metacognition were investigated. Results Adjusted multivariate regression analyses showed that child sex modified the associations between maternal postnatal BPA and changes in executive function. Higher maternal postnatal BPA concentrations predicted increasing difficulties from age 2 to 4 in the domains of inhibitory self-control and emergent metacognition in female, but not male children. The other bisphenol concentrations were not associated with changes in executive function. Conclusion Due to the ubiquity of BPA exposure among breastfeeding women, these findings justify further investigation on the effects of postnatal bisphenol exposure on child cognitive development. Impact Higher concentrations of maternal BPA at 3-month postpartum were associated with increasing difficulties in inhibitory self-control and emergent metacognition from age 2 to 4 in girls, but not boys. Prenatal BPA and prenatal/postnatal BPS were not significant predictors of changes in executive function in boys and girls. The current study extends previous research to show that maternal postnatal BPA could also impact child executive function. Due to the ubiquity of BPA exposure among breastfeeding women, the current findings suggest that additional precautions may be needed to protect infants' neurodevelopment from indirect exposure to BPA.

  • 240. England-Mason, Gillian
    et al.
    Martin, Jonathan W.
    Stockholm University, Science for Life Laboratory (SciLifeLab). Stockholm University, Faculty of Science, Department of Environmental Science and Analytical Chemistry. University of Alberta, Canada.
    MacDonald, Amy
    Kinniburgh, David
    Giesbrecht, Gerald F.
    Letourneau, Nicole
    Dewey, Deborah
    Similar names, different results: Consistency of the associations between prenatal exposure to phthalates and parent-ratings of behavior problems in preschool children2020In: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 142, article id 105892Article in journal (Refereed)
    Abstract [en]

    Background: Environmental health research has reported mixed findings on the associations between prenatal exposure to phthalates and parent-ratings of child behavioral problems.

    Objective: We examined the consistency of the associations between prenatal urinary phthalate concentrations and child behavior scores across two standardized instruments - the Behavior Assessment System for Children-Second Edition (BASC-2) and the Child Behavior Checklist (CBCL) - using two analytical approaches used to correct for urine dilution.

    Method: A sample of 351 mother-child pairs were selected from a prospective birth cohort of pregnant women enrolled between 2009 and 2012. Women provided spot urine samples during the second trimester of pregnancy, which were analyzed for levels of nine urinary phthalate metabolites. When their typically developing children were 3-4 years of age, mothers completed the BASC-2 and CBCL on the same day. Adjusted regression analyses examined the associations between maternal prenatal phthalate concentrations and child behavior scores on the BASC-2 and CBCL. To correct for urine dilution, primary regression analyses included urinary creatinine concentration as a separate independent variable (i.e., covariate). In the secondary regression analyses, creatinine-adjusted phthalate concentrations were used.

    Results: Primary logistic regression analyses that included urinary creatinine as a covariate showed that higher prenatal phthalate concentrations were related to increased odds of scores falling into the borderline or clinical range on the Hyperactivity, Aggression, Anxiety, Depression, Withdrawal, Externalizing Problems, Internalizing Problems, and Behavioral Symptoms Index scales on the BASC-2 (ORs from 1.39 to 2.07), but only the Anxious/ Depressed and Externalizing Problems scales on the CBCL (ORs from 1.80 to 3.28). Primary linear regression analyses showed that higher prenatal phthalate concentrations were related to higher scores on the Externalizing Problems (beta's = 0.16), Internalizing Problems (beta's from 0.16 to 0.20), and Behavioral Symptoms Index (beta's from 0.18 to 0.21) scales on the BASC-2, but not related to any CBCL scales. Sex-stratified analyses found that many associations were only significant for male children. Secondary analyses using creatinine-adjusted phthalate concentrations revealed that some of the associations from the primary analyses remained significant; however, a number of unique associations were observed.

    Conclusion: Prenatal phthalate exposure was associated with preschool behavioral development; however, findings were not consistent for the BASC-2 and CBCL, especially related to the clinical/syndrome scales and Internalizing Problems scale. Further, many findings differed based on the analytical approach used to correct for urine dilution. Future work is needed to delineate the similarities and differences between similarly named child behavior constructs assessed by different neurodevelopmental assessments. Also, research is needed to better understand why and how different analytical approaches influence the reported associations between maternal prenatal phthalate concentrations and children's behavior problems.

  • 241. England-Mason, Gillian
    et al.
    Merrill, Sarah M.
    Gladish, Nicole
    Moore, Sarah R.
    Giesbrecht, Gerald F.
    Letourneau, Nicole
    MacIsaac, Julia L.
    MacDonald, Amy M.
    Kinniburgh, David W.
    Ponsonby, Anne-Louise
    Saffery, Richard
    Martin, Jonathan W.
    Stockholm University, Faculty of Science, Department of Environmental Science. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Kobor, Michael S.
    Dewey, Deborah
    Prenatal exposure to phthalates and peripheral blood and buccal epithelial DNA methylation in infants: An epigenome-wide association study2022In: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 163, article id 107183Article in journal (Refereed)
    Abstract [en]

    Background: Prenatal exposure to phthalates has been associated with adverse health and neurodevelopmental outcomes. DNA methylation (DNAm) alterations may be a mechanism underlying these effects, but prior investigations of prenatal exposure to phthalates and neonatal DNAm profiles are limited to placental tissue and umbilical cord blood.

    Objective: Conduct an epigenome-wide association study (EWAS) of the associations between prenatal exposure to phthalates and DNAm in two accessible infant tissues, venous buffy coat blood and buccal epithelial cells (BECs).

    Methods: Participants included 152 maternal-infant pairs from the Alberta Pregnancy Outcomes and Nutrition (APrON) study. Maternal second trimester urine samples were analyzed for nine phthalate metabolites. Blood (n = 74) or BECs (n = 78) were collected from 3-month-old infants and profiled for DNAm using the Infinium HumanMethylation450 (450K) BeadChip. Robust linear regressions were used to investigate the associations between high (HMWPs) and low molecular weight phthalates (LMWPs) and change in methylation levels at variable Cytosine-phosphate-Guanine (CpG) sites in infant tissues, as well as the sensitivity of associations to potential confounders.

    Results: One candidate CpG in gene RNF39 reported by a previous study examining prenatal exposure to phthalates and cord blood DNAm was replicated. The EWAS identified 12 high-confidence CpGs in blood and another 12 in BECs associated with HMWPs and/or LMWPs. Prenatal exposure to bisphenol A (BPA) associated with two of the CpGs associated with HMWPs in BECs.

    Discussion: Prenatal exposure to phthalates was associated with DNAm variation at CpGs annotated to genes associated with endocrine hormone activity (i.e., SLCO4A1, TPO), immune pathways and DNA damage (i.e., RASGEF1B, KAZN, HLA-A, MYO18A, DIP2C, C1or109), and neurodevelopment (i.e., AMPH, NOTCH3, DNAJC5). Future studies that characterize the stability of these associations in larger samples, multiple cohorts, across tissues, and investigate the potential associations between these biomarkers and relevant health and neurodevelopmental outcomes are needed.

  • 242. Engström, Anna
    et al.
    Gómez de la Torre, Teresa Zardán
    Strømme, Maria
    Nilsson, Mats E.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Herthnek, David
    Detection of Rifampicin Resistance in Mycobacterium tuberculosis by Padlock Probes and Magnetic Nanobead-Based Readout2013In: PLOS ONE, E-ISSN 1932-6203, Vol. 8, no 4, article id e62015Article in journal (Refereed)
    Abstract [en]

    Control of the global epidemic tuberculosis is severely hampered by the emergence of drug-resistant Mycobacterium tuberculosis strains. Molecular methods offer a more rapid means of characterizing resistant strains than phenotypic drug susceptibility testing. We have developed a molecular method for detection of rifampicin-resistant M. tuberculosis based on padlock probes and magnetic nanobeads. Padlock probes were designed to target the most common mutations associated with rifampicin resistance in M. tuberculosis, i.e. at codons 516, 526 and 531 in the gene rpoB. For detection of the wild type sequence at all three codons simultaneously, a padlock probe and two gap-fill oligonucleotides were used in a novel assay configuration, requiring three ligation events for circularization. The assay also includes a probe for identification of the M. tuberculosis complex. Circularized probes were amplified by rolling circle amplification. Amplification products were coupled to oligonucleotide-conjugated magnetic nanobeads and detected by measuring the frequency-dependent magnetic response of the beads using a portable AC susceptometer.

  • 243. Engström, Karin
    et al.
    Wojdacz, Tomasz K.
    Marabita, Francesco
    Ewels, Philip
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Kaller, Max
    Vezzi, Francesco
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Prezza, Nicola
    Gruselius, Joel
    Vahter, Marie
    Broberg, Karin
    Transcriptomics and methylomics of CD4-positive T cells in arsenic-exposed women2017In: Archives of Toxicology, ISSN 0340-5761, E-ISSN 1432-0738, Vol. 91, no 5, p. 2067-2078Article in journal (Refereed)
    Abstract [en]

    Arsenic, a carcinogen with immunotoxic effects, is a common contaminant of drinking water and certain food worldwide. We hypothesized that chronic arsenic exposure alters gene expression, potentially by altering DNA methylation of genes encoding central components of the immune system. We therefore analyzed the transcriptomes (by RNA sequencing) and methylomes (by target-enrichment next-generation sequencing) of primary CD4-positive T cells from matched groups of four women each in the Argentinean Andes, with fivefold differences in urinary arsenic concentrations (median concentrations of urinary arsenic in the lower- and high-arsenic groups: 65 and 276 mu g/l, respectively). Arsenic exposure was associated with genome-wide alterations of gene expression; principal component analysis indicated that the exposure explained 53% of the variance in gene expression among the top variable genes and 19% of 28,351 genes were differentially expressed (false discovery rate < 0.05) between the exposure groups. Key genes regulating the immune system, such as tumor necrosis factor alpha and interferon gamma, as well as genes related to the NF-kappa-beta complex, were significantly downregulated in the high-arsenic group. Arsenic exposure was associated with genome-wide DNA methylation; the high-arsenic group had 3% points higher genome-wide full methylation (> 80% methylation) than the lower-arsenic group. Differentially methylated regions that were hyper-methylated in the high-arsenic group showed enrichment for immune-related gene ontologies that constitute the basic functions of CD4-positive T cells, such as isotype switching and lymphocyte activation and differentiation. In conclusion, chronic arsenic exposure from drinking water was related to changes in the transcriptome and methylome of CD4-positive T cells, both genome wide and in specific genes, supporting the hypothesis that arsenic causes immunotoxicity by interfering with gene expression and regulation.

  • 244.
    Eriksson, Olivia
    et al.
    Stockholm University, Faculty of Science, Numerical Analysis and Computer Science (NADA). Stockholm University, Science for Life Laboratory (SciLifeLab). KTH Royal Institute of Technology, Sweden; Swedish e-Science Research Centre (SeRC), Sweden.
    Jauhiainen, Alexandra
    Sasane, Sara Maad
    Kramer, Andrei
    Nair, Anu G.
    Sartorius, Carolina
    Hellgren Kotaleski, Jeanette
    Stockholm University, Faculty of Science, Numerical Analysis and Computer Science (NADA). Stockholm University, Science for Life Laboratory (SciLifeLab). KTH Royal Institute of Technology, Sweden; Swedish e-Science Research Centre (SeRC), Sweden.
    Uncertainty quantification, propagation and characterization by Bayesian analysis combined with global sensitivity analysis applied to dynamical intracellular pathway models2019In: Bioinformatics, ISSN 1367-4803, E-ISSN 1367-4811, Vol. 35, no 2, p. 284-292Article in journal (Refereed)
    Abstract [en]

    Motivation: Dynamical models describing intracellular phenomena are increasing in size and complexity as more information is obtained from experiments. These models are often over-parameterized with respect to the quantitative data used for parameter estimation, resulting in uncertainty in the individual parameter estimates as well as in the predictions made from the model. Here we combine Bayesian analysis with global sensitivity analysis (GSA) in order to give better informed predictions; to point out weaker parts of the model that are important targets for further experiments, as well as to give guidance on parameters that are essential in distinguishing different qualitative output behaviours.

    Results: We used approximate Bayesian computation (ABC) to estimate the model parameters from experimental data, as well as to quantify the uncertainty in this estimation (inverse uncertainty quantification), resulting in a posterior distribution for the parameters. This parameter uncertainty was next propagated to a corresponding uncertainty in the predictions (forward uncertainty propagation), and a GSA was performed on the predictions using the posterior distribution as the possible values for the parameters. This methodology was applied on a relatively large model relevant for synaptic plasticity, using experimental data from several sources. We could hereby point out those parameters that by themselves have the largest contribution to the uncertainty of the prediction as well as identify parameters important to separate between qualitatively different predictions. This approach is useful both for experimental design as well as model building.

  • 245. Ernits, Karin
    et al.
    Saha, Chayan Kumar
    Brodiazhenko, Tetiana
    Chouhan, Bhanu
    Shenoy, Aditi
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Buttress, Jessica A.
    Duque-Pedraza, Julián J.
    Bojar, Veda
    Nakamoto, Jose A.
    Kurata, Tatsuaki
    Egorov, Artyom A.
    Shyrokova, Lena
    Johansson, Marcus J. O.
    Mets, Toomas
    Rustamova, Aytan
    Džigurski, Jelisaveta
    Tenson, Tanel
    Garcia-Pino, Abel
    Strahl, Henrik
    Elofsson, Arne
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Hauryliuk, Vasili
    Atkinson, Gemma C.
    The structural basis of hyperpromiscuity in a core combinatorial network of type II toxin–antitoxin and related phage defense systems2023In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 120, no 33, article id e2305393120Article in journal (Refereed)
    Abstract [en]

    Toxin-antitoxin (TA) systems are a large group of small genetic modules found in prokaryotes and their mobile genetic elements. Type II TAs are encoded as bicistronic (two-gene) operons that encode two proteins: a toxin and a neutralizing antitoxin. Using our tool NetFlax (standing for Network-FlaGs for toxins and antitoxins), we have performed a large-scale bioinformatic analysis of proteinaceous TAs, revealing interconnected clusters constituting a core network of TA-like gene pairs. To understand the structural basis of toxin neutralization by antitoxins, we have predicted the structures of 3,419 complexes with AlphaFold2. Together with mutagenesis and functional assays, our structural predictions provide insights into the neutralizing mechanism of the hyperpromiscuous Panacea antitoxin domain. In antitoxins composed of standalone Panacea, the domain mediates direct toxin neutralization, while in multidomain antitoxins the neutralization is mediated by other domains, such as PAD1, Phd-C, and ZFD. We hypothesize that Panacea acts as a sensor that regulates TA activation. We have experimentally validated 16 NetFlax TA systems and used domain annotations and metabolic labeling assays to predict their potential mechanisms of toxicity (such as membrane disruption, and inhibition of cell division or protein synthesis) as well as biological functions (such as antiphage defense). We have validated the antiphage activity of a RosmerTA system encoded by Gordonia phage Kita, and used fluorescence microscopy to confirm its predicted membrane-depolarizing activity. The interactive version of the NetFlax TA network that includes structural predictions can be accessed at http://netflax.webflags.se/.

  • 246. Espeso-Gil, Sergio
    et al.
    Holik, Aliaksei Z.
    Bonnin, Sarah
    Jhanwar, Shalu
    Chandrasekaran, Sandhya
    Pique-Regi, Roger
    Albaiges-Rafols, Julia
    Maher, Michael
    Permanyer, Jon
    Irimia, Manuel
    Friedländer, Marc R.
    Stockholm University, Science for Life Laboratory (SciLifeLab). Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
    Pons-Espinal, Meritxell
    Akbarian, Schahram
    Dierssen, Mara
    Maass, Philipp G.
    Hor, Charlotte N.
    Ossowski, Stephan
    Environmental Enrichment Induces Epigenomic and Genome Organization Changes Relevant for Cognition2021In: Frontiers in Molecular Neuroscience, ISSN 1662-5099, Vol. 14, article id 664912Article in journal (Refereed)
    Abstract [en]

    In early development, the environment triggers mnemonic epigenomic programs resulting in memory and learning experiences to confer cognitive phenotypes into adulthood. To uncover how environmental stimulation impacts the epigenome and genome organization, we used the paradigm of environmental enrichment (EE) in young mice constantly receiving novel stimulation. We profiled epigenome and chromatin architecture in whole cortex and sorted neurons by deep-sequencing techniques. Specifically, we studied chromatin accessibility, gene and protein regulation, and 3D genome conformation, combined with predicted enhancer and chromatin interactions. We identified increased chromatin accessibility, transcription factor binding including CTCF-mediated insulation, differential occupancy of H3K36me3 and H3K79me2, and changes in transcriptional programs required for neuronal development. EE stimuli led to local genome re-organization by inducing increased contacts between chromosomes 7 and 17 (inter-chromosomal). Our findings support the notion that EE-induced learning and memory processes are directly associated with the epigenome and genome organization.

  • 247. Estrella Alcamán, María
    et al.
    Fernandez, Camila
    Delgado, Antonio
    Bergman, Birgitta
    Stockholm University, Faculty of Science, Department of Ecology, Environment and Plant Sciences. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Diez, Beatriz
    The cyanobacterium Mastigocladus fulfills the nitrogen demand of a terrestrial hot spring microbial mat2015In: The ISME Journal, ISSN 1751-7362, E-ISSN 1751-7370, Vol. 9, no 10, p. 2290-2303Article in journal (Refereed)
    Abstract [en]

    Cyanobacteria from Subsection V (Stigonematales) are important components of microbial mats in non-acidic terrestrial hot springs. Despite their diazotrophic nature (N-2 fixers), their impact on the nitrogen cycle in such extreme ecosystems remains unknown. Here, we surveyed the identity and activity of diazotrophic cyanobacteria in the neutral hot spring of Porcelana (Northern Patagonia, Chile) during 2009 and 2011-2013. We used 16S rRNA and the nifH gene to analyze the distribution and diversity of diazotrophic cyanobacteria. Our results demonstrate the dominance of the heterocystous genus Mastigocladus (Stigonematales) along the entire temperature gradient of the hot spring (69-38 degrees C). In situ nitrogenase activity (acetylene reduction), nitrogen fixation rates (cellular uptake of N-15(2)) and nifH transcription levels in the microbial mats showed that nitrogen fixation and nifH mRNA expression were light-dependent. Nitrogen fixation activities were detected at temperatures ranging from 58 degrees C to 46 degrees C, with maximum daily rates of 600 nmol C2H4 cm(-2) per day and 94.1 nmol N cm(-2) per day. These activity patterns strongly suggest a heterocystous cyanobacterial origin and reveal a correlation between nitrogenase activity and nifH gene expression during diurnal cycles in thermal microbial mats. N and C fixation in the mats contributed similar to 3 g Nm(-2) per year and 27 g Cm-2 per year, suggesting that these vital demands are fully met by the diazotrophic and photoautotrophic capacities of the cyanobacteria in the Porcelana hot spring.

  • 248. Evkaikina, Anastasiia I.
    et al.
    Berke, Lidija
    Romanova, Marina A.
    Proux-Wéra, Estelle
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab). Swedish University of Agricultural Sciences, Sweden.
    Ivanova, Alexandra N.
    Rydin, Catarina
    Stockholm University, Faculty of Science, Department of Ecology, Environment and Plant Sciences.
    Pawlowski, Katharina
    Stockholm University, Faculty of Science, Department of Ecology, Environment and Plant Sciences.
    Voitsekhovskaja, Olga V.
    The Huperzia selago Shoot Tip Transcriptome Sheds New Light on the Evolution of Leaves2017In: Genome Biology and Evolution, ISSN 1759-6653, E-ISSN 1759-6653, Vol. 9, no 9, p. 2444-2460Article in journal (Refereed)
    Abstract [en]

    Lycopodiophyta-consisting of three orders, Lycopodiales, Isoetales and Selaginellales, with different types of shoot apical meristems (SAMs)-form the earliest branch among the extant vascular plants. They represent a sister group to all other vascular plants, from which they differ in that their leaves are microphylls-that is, leaves with a single, unbranched vein, emerging from the protostele without a leaf gap-not megaphylls. All leaves represent determinate organs originating on the flanks of indeterminate SAMs. Thus, leaf formation requires the suppression of indeterminacy, that is, of KNOX transcription factors. In seed plants, this is mediated by different groups of transcription factors including ARP and YABBY. We generated a shoot tip transcriptome of Huperzia selago (Lycopodiales) to examine the genes involved in leaf formation. Our H. selago transcriptome does not contain any ARP homolog, although transcriptomes of Selaginella spp. do. Surprisingly, we discovered a YABBY homolog, although these transcription factors were assumed to have evolved only in seed plants. The existence of a YABBY homolog in H. selago suggests that YABBY evolved already in the common ancestor of the vascular plants, and subsequently was lost in some lineages like Selaginellales, whereas ARP may have been lost in Lycopodiales. The presence of YABBY in the common ancestor of vascular plants would also support the hypothesis that this common ancestor had a simplex SAM. Furthermore, a comparison of the expression patterns of ARP in shoot tips of Selaginella kraussiana (Harrison CJ, et al. 2005. Independent recruitment of a conserved developmental mechanism during leaf evolution. Nature 434(7032): 509-514.) and YABBY in shoot tips of H. selago implies that the development of microphylls, unlike megaphylls, does not seem to depend on the combined activities of ARP and YABBY. Altogether, our data show that Lycopodiophyta are a diverse group; so, in order to understand the role of Lycopodiophyta in evolution, representatives of Lycopodiales, Selaginellales, as well as of Isoetales, have to be examined.

  • 249.
    Ewels, Philip
    et al.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Magnusson, Måns
    Lundin, Sverker
    Käller, Max
    MultiQC: summarize analysis results for multiple tools and samples in a single report2016In: Bioinformatics, ISSN 1367-4803, E-ISSN 1367-4811, Vol. 32, no 19, p. 3047-3048Article in journal (Refereed)
    Abstract [en]

    Motivation: Fast and accurate quality control is essential for studies involving next-generation sequencing data. Whilst numerous tools exist to quantify QC metrics, there is no common approach to flexibly integrate these across tools and large sample sets. Assessing analysis results across an entire project can be time consuming and error prone; batch effects and outlier samples can easily be missed in the early stages of analysis.

    Results: We present MultiQC, a tool to create a single report visualising output from multiple tools across many samples, enabling global trends and biases to be quickly identified. MultiQC can plot data from many common bioinformatics tools and is built to allow easy extension and customization.

  • 250.
    Ewels, Philip
    et al.
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm University, Science for Life Laboratory (SciLifeLab).
    Sikora, Thierry
    Serin, Virginie
    Ewels, Chris P.
    Lajaunie, Luc
    A Complete Overhaul of the Electron Energy-Loss Spectroscopy and X-Ray Absorption Spectroscopy Database: eelsdb.eu2016In: Microscopy and Microanalysis, ISSN 1431-9276, E-ISSN 1435-8115, Vol. 22, no 3, p. 717-724Article in journal (Refereed)
    Abstract [en]

    The electron energy-loss spectroscopy (EELS) and X-ray absorption spectroscopy (XAS) database has been completely rewritten, with an improved design, user interface, and a number of new tools. The database is accessible at https://eelsdb.eu/ and can now be used without registration. The submission process has been streamlined to encourage spectrum submissions and the new design gives greater emphasis on contributors' original work by highlighting their papers. With numerous new filters and a powerful search function, it is now simple to explore the database of several hundred EELS and XAS spectra. Interactive plots allow spectra to be overlaid, facilitating online comparison. An application-programming interface has been created, allowing external tools and software to easily access the information held within the database. In addition to the database itself, users can post and manage job adverts and read the latest news and events regarding the EELS and XAS communities. In accordance with the ongoing drive toward open access data increasingly demanded by funding bodies, the database will facilitate open access data sharing of EELS and XAS spectra.

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