uu.seUppsala universitets publikationer
Ändra sökning
Avgränsa sökresultatet
45678910 301 - 350 av 3252
RefereraExporteraLänk till träfflistan
Permanent länk
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Träffar per sida
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sortering
  • Standard (Relevans)
  • Författare A-Ö
  • Författare Ö-A
  • Titel A-Ö
  • Titel Ö-A
  • Publikationstyp A-Ö
  • Publikationstyp Ö-A
  • Äldst först
  • Nyast först
  • Skapad (Äldst först)
  • Skapad (Nyast först)
  • Senast uppdaterad (Äldst först)
  • Senast uppdaterad (Nyast först)
  • Disputationsdatum (tidigaste först)
  • Disputationsdatum (senaste först)
  • Standard (Relevans)
  • Författare A-Ö
  • Författare Ö-A
  • Titel A-Ö
  • Titel Ö-A
  • Publikationstyp A-Ö
  • Publikationstyp Ö-A
  • Äldst först
  • Nyast först
  • Skapad (Äldst först)
  • Skapad (Nyast först)
  • Senast uppdaterad (Äldst först)
  • Senast uppdaterad (Nyast först)
  • Disputationsdatum (tidigaste först)
  • Disputationsdatum (senaste först)
Markera
Maxantalet träffar du kan exportera från sökgränssnittet är 250. Vid större uttag använd dig av utsökningar.
  • 301.
    Berggren, Sofia
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi.
    Validation and characterisation of a micro-protein in Campylobacter jejuni2017Självständigt arbete på avancerad nivå (yrkesexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
    Abstract [en]

    The Epsilonproteobacterium Campylobacter jejuni is a major foodborne pathogen in humans mainly causing gastroenteritis, and is connected to several secondary autoimmune diseases. A large part of the small genome of C. jejuni is still to be characterized, with many hypothetical proteins present. Micro-proteins - those that are < 50 amino acids and encoded by a small open-reading frame (micro-ORF) - are an understudied class of proteins that have been shown to be involved in vital processes in the cell, such as cell division, modulation of enzymatic activities, and stress responses. So far, few examples of micro-proteins are known in pathogenic bacteria, and fewer are known that affect virulence. In this study, we provide first evidence that the conserved micro-ORF Cj0878 of C. jejuni is translated by showing that a GFP translational fusion to the ORF is translated, and that Cj0878 mRNA and protein levels are affected by the absence of iron in minimal media. With in silico analysis we found that Cj0878 is likely a highly basic protein and may have an amphipathic nature. We also show that a predicted base-pairing interaction between Cj0878 mRNA and the sRNA CJnc170 likely has a regulatory consequence, by showing that CJnc170 mutant strains have different levels of the Cj0878 translational fusion protein. To summarise this study provides the first validation and characterisation of a micro-protein in the important pathogen C. jejuni, and provides the basis for future studies on the function of the protein.

    Publikationen är tillgänglig i fulltext från 2020-02-01 00:00
  • 302.
    Bergh, Magnus
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Biologiska sektionen, Institutionen för cell- och molekylärbiologi.
    Interaction of Ultrashort X-ray Pulses with Material2007Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Radiation damage limits the resolution in imaging experiments. Damage is caused by energy deposited into the sample during exposure. Ultrashort and extremely bright X-ray pulses from free-electron lasers (FELs) offer the possibility to outrun key damage processes, and temporarily improve radiation tolerance. Theoretical models indicate that high detail-resolutions could be realized on non-crystalline samples with very short pulses, before plasma expansion.

    Studies presented here describe the interaction of a very intense and ultrashort X-ray pulse with material, and investigate boundary conditions for flash diffractive imaging both theoretically and experimentally. In the hard X-ray regime, predictions are based on particle simulations with a continuum formulation that accounts for screening from free electrons.

    First experimental results from the first soft X-ray free-electron laser, the FLASH facility in Hamburg, confirm the principle of flash imaging, and provide the first validation of our theoretical models. Specifically, experiments on nano-fabricated test objects show that an interpretable image can be obtained to high resolution before the sample is vaporized. Radiation intensity in these experiments reached 10^14 W/cm^2, and the temperature of the sample rose to 60000 Kelvin after the 25 femtosecond pulse left the sample. Further experiments with time-delay X-ray holography follow the explosion dynamics over some picoseconds after illumination.

    Finally, this thesis presents results from biological flash-imaging studies on living cells. The model is based on plasma calculations and fluid-like motions of the sample, supported by the time-delay measurements. This study provides an estimate for the achievable resolutions as function of wavelength and pulse length. The technique was demonstrated by our team in an experiment where living cells were exposed to a single shot from the FLASH soft X-ray laser.

    Delarbeten
    1. Model for the Dynamics of a Water Cluster in an X-ray Free Electron Laser Beam
    Öppna denna publikation i ny flik eller fönster >>Model for the Dynamics of a Water Cluster in an X-ray Free Electron Laser Beam
    2004 (Engelska)Ingår i: Physical Review E. Statistical, Nonlinear, and Soft Matter Physics, ISSN 1539-3755, E-ISSN 1550-2376, Vol. 70, nr 5:1, s. 051904-Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    A microscopic sample placed into a focused x-ray free electron laser beam will explode due to strong ionization on a femtosecond time scale. The dynamics of this Coulomb explosion has been modeled by Neutze et al. [Nature (London) 406, 752 (2000)] for a protein, using computer simulations. The results suggest that by using ultrashort exposures, structural information may be collected before the sample is destroyed due to radiation damage. In this paper a method is presented to include the effect of screening by free electrons in the sample in a molecular dynamics simulation. The electrons are approximated by a classical gas, and the electron distribution is calculated iteratively from the Poisson-Boltzmann equation. Test simulations of water clusters reveal the details of the explosion dynamics, as well as the evolution of the free electron gas during the beam exposure. We find that inclusion of the electron gas in the model slows down the Coulomb explosion. The hydrogen atoms leave the sample faster than the oxygen atoms, leading to a double layer of positive ions. A considerable electron density is located between these two layers. The fact that the hydrogens are found to explode much faster than the oxygens means that the diffracting part of the sample stays intact somewhat longer than the sample as a whole.

    Nyckelord
    Computer Simulation, Electrons, Lasers, Models
    Nationell ämneskategori
    Naturvetenskap
    Identifikatorer
    urn:nbn:se:uu:diva-96323 (URN)15600653 (PubMedID)
    Tillgänglig från: 2007-10-24 Skapad: 2007-10-24 Senast uppdaterad: 2017-12-14Bibliografiskt granskad
    2. Soft-x-ray free-electron-laser interaction with materials
    Öppna denna publikation i ny flik eller fönster >>Soft-x-ray free-electron-laser interaction with materials
    2007 (Engelska)Ingår i: Physical Review E. Statistical, Nonlinear, and Soft Matter Physics: Statistical Physics, Plasmas, Fluids, and Related Interdisciplinary Topics, ISSN 1063-651X, E-ISSN 1095-3787, Vol. 76, nr 4, s. 046403-Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Soft-x-ray free-electron lasers have enabled materials studies in which structural information is obtained faster than the relevant probe-induced damage mechanisms. We present a continuum model to describe the damage process based on hot-dense plasma theory, which includes a description of the energy deposition in the samples, the subsequent dynamics of the sample, and the detector signal. We compared the model predictions with experimental data and mostly found reasonable agreement. In view of future free-electron-laser performance, the model was also used to predict damage dynamics of samples and optical elements at shorter wavelengths and larger photon fluences than currently available.

    Nationell ämneskategori
    Fysik
    Identifikatorer
    urn:nbn:se:uu:diva-96324 (URN)10.1103/PhysRevE.76.046403 (DOI)000250622100073 ()
    Tillgänglig från: 2007-10-24 Skapad: 2007-10-24 Senast uppdaterad: 2017-12-14Bibliografiskt granskad
    3. Force Field Benchmark of Organic Liquids: Density, Enthalpy of Vaporization, Heat Capacities, Surface Tension, Isothermal Compressibility, Volumetric Expansion Coefficient, and Dielectric Constant
    Öppna denna publikation i ny flik eller fönster >>Force Field Benchmark of Organic Liquids: Density, Enthalpy of Vaporization, Heat Capacities, Surface Tension, Isothermal Compressibility, Volumetric Expansion Coefficient, and Dielectric Constant
    Visa övriga...
    2007 (Engelska)Ingår i: Physical Review Letters, ISSN 0031-9007, E-ISSN 1079-7114, Vol. 98, nr 14, s. 145502-Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    At the recently built FLASH x-ray free-electron laser, we studied the reflectivity of Si/C multilayers with fluxes up to 3×1014W/cm2. Even though the nanostructures were ultimately completely destroyed, we found that they maintained their integrity and reflectance characteristics during the 25-fs-long pulse, with no evidence for any structural changes over lengths greater than 3Å. This experiment demonstrates that with intense ultrafast pulses, structural damage does not occur during the pulse, giving credence to the concept of diffraction imaging of single macromolecules.

    Nyckelord
    X-ray effects, Optical properties of low-dimensional, mesoscopic, and nanoscale materials and structures
    Nationell ämneskategori
    Biologiska vetenskaper Fysik
    Identifikatorer
    urn:nbn:se:uu:diva-96325 (URN)10.1103/PhysRevLett.98.145502 (DOI)000245512100037 ()
    Anmärkning


    Tillgänglig från: 2007-10-24 Skapad: 2007-10-24 Senast uppdaterad: 2017-12-14Bibliografiskt granskad
    4. Feasibility of imaging living cells at subnanometer resolutions by ultrafast X-ray diffraction
    Öppna denna publikation i ny flik eller fönster >>Feasibility of imaging living cells at subnanometer resolutions by ultrafast X-ray diffraction
    Visa övriga...
    2008 (Engelska)Ingår i: Quarterly reviews of biophysics (Print), ISSN 0033-5835, E-ISSN 1469-8994, Vol. 41, nr 3-4, s. 181-204Artikel, forskningsöversikt (Refereegranskat) Published
    Abstract [en]

    Detailed structural investigations on living cells are problematic because existing structural methods cannot reach high resolutions on non-reproducible objects. Illumination with an ultrashort and extremely bright X-ray pulse can outrun key damage processes over a very short period. This can be exploited to extend the diffraction signal to the highest possible resolution in flash diffraction experiments. Here we present an analysis or the interaction of a very intense and very short X-ray pulse with a living cell, using a non-equilibrium population kinetics plasma code with radiation transfer. Each element in the evolving plasma is modeled by numerous states to monitor changes in the atomic populations as a function of pulse length, wavelength, and fluence. The model treats photoionization, impact ionization, Auger decay, recombination, and inverse bremsstrahlung by solving rate equations in a self-consistent manner and describes hydrodynamic expansion through the ion sound speed, The results show that subnanometer resolutions could be reached on micron-sized cells in a diffraction-limited geometry at wavelengths between 0.75 and 1.5 nm and at fluences of 10(11)-10(12) photonS mu M (2) in less than 10 fs. Subnanometer resolutions could also be achieved with harder X-rays at higher fluences. We discuss experimental and computational strategies to obtain depth information about the object in flash diffraction experiments.

    Nationell ämneskategori
    Naturvetenskap
    Identifikatorer
    urn:nbn:se:uu:diva-96326 (URN)10.1017/S003358350800471X (DOI)000262098500001 ()
    Tillgänglig från: 2007-10-24 Skapad: 2007-10-24 Senast uppdaterad: 2017-12-14Bibliografiskt granskad
    5. Interaction of Ultrashort X-ray Pulses with B4C, SiC and Si
    Öppna denna publikation i ny flik eller fönster >>Interaction of Ultrashort X-ray Pulses with B4C, SiC and Si
    2008 (Engelska)Ingår i: Physical Review E. Statistical, Nonlinear, and Soft Matter Physics: Statistical Physics, Plasmas, Fluids, and Related Interdisciplinary Topics, ISSN 1063-651X, E-ISSN 1095-3787, Vol. 77, nr 2, s. 026404-1-026404-8Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    The interaction of 32.5 and 6 nm ultrashort x-ray pulses with the solid materials B4C, SiC, and Si is simulated with a nonlocal thermodynamic equilibrium radiation transfer code. We study the ionization dynamics as a function of depth in the material and modifications of the opacity during irradiation, and estimate the crater depth. Furthermore, we compare the estimated crater depth with experimental data, for fluences up to 2.2 J/cm(2). Our results show that, at 32.5 nm irradiation, the opacity changes by less than a factor of 2 for B4C and Si and by a factor of 3 for SiC, for fluences up to 200 J/cm(2). At a laser wavelength of 6 nm, the model predicts a dramatic decrease in opacity due to the weak inverse bremsstrahlung, increasing the crater depth for high fluences.

    Nyckelord
    boron compounds, bremsstrahlung, elemental semiconductors, high-speed optical techniques, ionisation, laser beam effects, opacity, silicon, silicon compounds, thermodynamics, wide band gap semiconductors, X-ray effects
    Nationell ämneskategori
    Biologiska vetenskaper
    Identifikatorer
    urn:nbn:se:uu:diva-96327 (URN)10.1103/PhysRevE.77.026404 (DOI)000253763800053 ()18352130 (PubMedID)
    Tillgänglig från: 2007-10-24 Skapad: 2007-10-24 Senast uppdaterad: 2017-12-14Bibliografiskt granskad
  • 303.
    Bergh, Magnus
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär biofysik.
    Huldt, Gösta
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär biofysik.
    Timneanu, Nicusor
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär biofysik.
    Maia, Filipe R. N. C.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär biofysik.
    Hajdu, Janos
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär biofysik.
    Feasibility of imaging living cells at subnanometer resolutions by ultrafast X-ray diffraction2008Ingår i: Quarterly reviews of biophysics (Print), ISSN 0033-5835, E-ISSN 1469-8994, Vol. 41, nr 3-4, s. 181-204Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Detailed structural investigations on living cells are problematic because existing structural methods cannot reach high resolutions on non-reproducible objects. Illumination with an ultrashort and extremely bright X-ray pulse can outrun key damage processes over a very short period. This can be exploited to extend the diffraction signal to the highest possible resolution in flash diffraction experiments. Here we present an analysis or the interaction of a very intense and very short X-ray pulse with a living cell, using a non-equilibrium population kinetics plasma code with radiation transfer. Each element in the evolving plasma is modeled by numerous states to monitor changes in the atomic populations as a function of pulse length, wavelength, and fluence. The model treats photoionization, impact ionization, Auger decay, recombination, and inverse bremsstrahlung by solving rate equations in a self-consistent manner and describes hydrodynamic expansion through the ion sound speed, The results show that subnanometer resolutions could be reached on micron-sized cells in a diffraction-limited geometry at wavelengths between 0.75 and 1.5 nm and at fluences of 10(11)-10(12) photonS mu M (2) in less than 10 fs. Subnanometer resolutions could also be achieved with harder X-rays at higher fluences. We discuss experimental and computational strategies to obtain depth information about the object in flash diffraction experiments.

  • 304.
    Bergh, Magnus
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär biofysik.
    Timneanu, Nicusor
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär biofysik.
    Hau-Riege, S. P.
    Scott, H. A.
    Interaction of Ultrashort X-ray Pulses with B4C, SiC and Si2008Ingår i: Physical Review E. Statistical, Nonlinear, and Soft Matter Physics: Statistical Physics, Plasmas, Fluids, and Related Interdisciplinary Topics, ISSN 1063-651X, E-ISSN 1095-3787, Vol. 77, nr 2, s. 026404-1-026404-8Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The interaction of 32.5 and 6 nm ultrashort x-ray pulses with the solid materials B4C, SiC, and Si is simulated with a nonlocal thermodynamic equilibrium radiation transfer code. We study the ionization dynamics as a function of depth in the material and modifications of the opacity during irradiation, and estimate the crater depth. Furthermore, we compare the estimated crater depth with experimental data, for fluences up to 2.2 J/cm(2). Our results show that, at 32.5 nm irradiation, the opacity changes by less than a factor of 2 for B4C and Si and by a factor of 3 for SiC, for fluences up to 200 J/cm(2). At a laser wavelength of 6 nm, the model predicts a dramatic decrease in opacity due to the weak inverse bremsstrahlung, increasing the crater depth for high fluences.

  • 305.
    Bergh, Magnus
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi.
    Timneanu, Nicusor
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär biofysik.
    van der Spoel, David
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär biofysik.
    Model for the Dynamics of a Water Cluster in an X-ray Free Electron Laser Beam2004Ingår i: Physical Review E. Statistical, Nonlinear, and Soft Matter Physics, ISSN 1539-3755, E-ISSN 1550-2376, Vol. 70, nr 5:1, s. 051904-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A microscopic sample placed into a focused x-ray free electron laser beam will explode due to strong ionization on a femtosecond time scale. The dynamics of this Coulomb explosion has been modeled by Neutze et al. [Nature (London) 406, 752 (2000)] for a protein, using computer simulations. The results suggest that by using ultrashort exposures, structural information may be collected before the sample is destroyed due to radiation damage. In this paper a method is presented to include the effect of screening by free electrons in the sample in a molecular dynamics simulation. The electrons are approximated by a classical gas, and the electron distribution is calculated iteratively from the Poisson-Boltzmann equation. Test simulations of water clusters reveal the details of the explosion dynamics, as well as the evolution of the free electron gas during the beam exposure. We find that inclusion of the electron gas in the model slows down the Coulomb explosion. The hydrogen atoms leave the sample faster than the oxygen atoms, leading to a double layer of positive ions. A considerable electron density is located between these two layers. The fact that the hydrogens are found to explode much faster than the oxygens means that the diffracting part of the sample stays intact somewhat longer than the sample as a whole.

  • 306.
    Berghoff, Bork A.
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Mikrobiologi. Justus Liebig Univ, Inst Mikrobiol & Mol Biol, D-35392 Giessen, Germany..
    Hoekzema, Mirthe
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Mikrobiologi.
    Aulbach, Lena
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Mikrobiologi.
    Wagner, Gerhart E. H.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Mikrobiologi.
    Two regulatory RNA elements affect TisB-dependent depolarization and persister formation2017Ingår i: Molecular Microbiology, ISSN 0950-382X, E-ISSN 1365-2958, Vol. 103, nr 6, s. 1020-1033Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Bacterial survival strategies involve phenotypic diversity which is generated by regulatory factors and noisy expression of effector proteins. The question of how bacteria exploit regulatory RNAs to make decisions between phenotypes is central to a general understanding of these universal regulators. We investigated the TisB/IstR-1 toxin-antitoxin system of Escherichia coli to appreciate the role of the RNA antitoxin IstR-1 in TisB-dependent depolarization of the inner membrane and persister formation. Persisters are phenotypic variants that have become transiently drug-tolerant by arresting growth. The RNA antitoxin IstR-1 sets a threshold for TisB-dependent depolarization under DNA-damaging conditions, resulting in two sub-populations: polarized and depolarized cells. Furthermore, our data indicate that an inhibitory 5 UTR structure in the tisB mRNA serves as a regulatory RNA element that delays TisB translation to avoid inappropriate depolarization when DNA damage is low. Investigation of the persister sub-population further revealed that both regulatory RNA elements affect persister levels as well as persistence time. This work provides an intriguing example of how bacteria exploit regulatory RNAs to control phenotypic heterogeneity.

  • 307.
    Berghoff, Bork A.
    et al.
    Justus Liebig Univ, Inst Mikrobiol & Mol Biol, Giessen, Germany..
    Karlsson, Torgny
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi, Medicinsk genetik och genomik.
    Kallman, Thomas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Wagner, Gerhart E. H.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Mikrobiologi.
    Grabherr, Manfred G.
    Uppsala universitet, Science for Life Laboratory, SciLifeLab. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    RNA-sequence data normalization through in silico prediction of reference genes: the bacterial response to DNA damage as case study2017Ingår i: BioData Mining, ISSN 1756-0381, E-ISSN 1756-0381, Vol. 10, artikel-id 30Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Measuring how gene expression changes in the course of an experiment assesses how an organism responds on a molecular level. Sequencing of RNA molecules, and their subsequent quantification, aims to assess global gene expression changes on the RNA level (transcriptome). While advances in high-throughput RNA-sequencing (RNA-seq) technologies allow for inexpensive data generation, accurate post-processing and normalization across samples is required to eliminate any systematic noise introduced by the biochemical and/or technical processes. Existing methods thus either normalize on selected known reference genes that are invariant in expression across the experiment, assume that the majority of genes are invariant, or that the effects of up-and down-regulated genes cancel each other out during the normalization.

    Results: Here, we present a novel method, moose(2), which predicts invariant genes in silico through a dynamic programming (DP) scheme and applies a quadratic normalization based on this subset. The method allows for specifying a set of known or experimentally validated invariant genes, which guides the DP. We experimentally verified the predictions of this method in the bacterium Escherichia coli, and show how moose(2) is able to (i) estimate the expression value distances between RNA-seq samples, (ii) reduce the variation of expression values across all samples, and (iii) to subsequently reveal new functional groups of genes during the late stages of DNA damage. We further applied the method to three eukaryotic data sets, on which its performance compares favourably to other methods. The software is implemented in C++ and is publicly available from http://grabherr.github.io/moose2/.

    Conclusions: The proposed RNA-seq normalization method, moose(2), is a valuable alternative to existing methods, with two major advantages: (i) in silico prediction of invariant genes provides a list of potential reference genes for downstream analyses, and (ii) non-linear artefacts in RNA-seq data are handled adequately to minimize variations between replicates.

  • 308.
    Berghoff, Bork A.
    et al.
    Justus Liebig Univ, Inst Mikrobiol & Mol Biol, D-35392 Giessen, Germany..
    Wagner, Gerhart E. H.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi.
    RNA-based regulation in type I toxin-antitoxin systems and its implication for bacterial persistence2017Ingår i: Current Genetics, ISSN 0172-8083, E-ISSN 1432-0983, Vol. 63, nr 6, s. 1011-1016Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Bacterial dormancy is a valuable survival strategy upon challenging environmental conditions. Dormant cells tolerate the consequences of high stress levels and may re-populate the environment upon return to favorable conditions. Antibiotic-tolerant bacteria-termed persisters-regularly cause relapsing infections, increase the likelihood of antibiotic resistance, and, therefore, earn increasing attention. Their generation often depends on toxins from chromosomal toxin-antitoxin systems. Here, we review recent insights concerning RNA-based control of toxin synthesis, and discuss possible implications for persister generation.

  • 309.
    Bergin, Claudia
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär evolution. Uppsala universitet, Science for Life Laboratory, SciLifeLab. Max Planck Inst Marine Mikrobiol, Bremen, Germany.
    Wentrup, C.
    Max Planck Inst Marine Mikrobiol, Bremen, Germany.;Univ Vienna, Div Microbial Ecol, Dept Microbiol & Ecosyst Sci, Vienna, Austria..
    Brewig, N.
    Max Planck Inst Marine Mikrobiol, Bremen, Germany..
    Blazejak, A.
    Max Planck Inst Marine Mikrobiol, Bremen, Germany..
    Erseus, C.
    Univ Gothenburg, Dept Biol & Environm Sci, Gothenburg, Sweden..
    Giere, O.
    Univ Hamburg, Biozentrum Grindel, Zool Inst, Hamburg, Germany.;Univ Hamburg, Zool Museum, Hamburg, Germany..
    Schmid, M.
    Univ Vienna, Div Microbial Ecol, Dept Microbiol & Ecosyst Sci, Vienna, Austria..
    De Wit, P.
    Univ Gothenburg, Tjarmo Marine Lab, Dept Marine Sci, Stromstad, Sweden..
    Dubilier, N.
    Max Planck Inst Marine Mikrobiol, Bremen, Germany..
    Acquisition of a Novel Sulfur-Oxidizing Symbiont in the Gutless Marine Worm Inanidrilus exumae2018Ingår i: Applied and Environmental Microbiology, ISSN 0099-2240, E-ISSN 1098-5336, Vol. 84, nr 7, artikel-id e02267-17Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Gutless phallodrilines are marine annelid worms without a mouth or gut, which live in an obligate association with multiple bacterial endosymbionts that supply them with nutrition. In this study, we discovered an unusual symbiont community in the gutless phallodriline Inanidrilus exumae that differs markedly from the microbiomes of all 22 of the other host species examined. Comparative 16S rRNA gene sequence analysis and fluorescence in situ hybridization revealed that I. exumae harbors cooccurring gamma-, alpha-, and deltaproteobacterial symbionts, while all other known host species harbor gamma-and either alpha-or deltaproteobacterial symbionts. Surprisingly, the primary chemoautotrophic sulfur oxidizer "Candidatus Thiosymbion" that occurs in all other gutless phallodriline hosts does not appear to be present in I. exumae. Instead, I. exumae harbors a bacterial endosymbiont that resembles "Ca. Thiosymbion" morphologically and metabolically but originates from a novel lineage within the class Gammaproteo-bacteria. This endosymbiont, named Gamma 4 symbiont here, had a 16S rRNA gene sequence that differed by at least 7% from those of other free-living and symbiotic bacteria and by 10% from that of "Ca. Thiosymbion." Sulfur globules in the Gamma 4 symbiont cells, as well as the presence of genes characteristic for autotrophy (cbbL) and sulfur oxidation (aprA), indicate that this symbiont is a chemoautotrophic sulfur oxidizer. Our results suggest that a novel lineage of free-living bacteria was able to establish a stable and specific association with I. exumae and appears to have displaced the "Ca. Thiosymbion" symbionts originally associated with these hosts. IMPORTANCE All 22 gutless marine phallodriline species examined to date live in a highly specific association with endosymbiotic, chemoautotrophic sulfur oxidizers called "Ca. Thiosymbion." These symbionts evolved from a single common ancestor and represent the ancestral trait for this host group. They are transmitted vertically and assumed to be in transition to becoming obligate endosymbionts. It is therefore surprising that despite this ancient, evolutionary relationship between phallodriline hosts and "Ca. Thiosymbion," these symbionts are apparently no longer present in Inanidrilus exumae. They appear to have been displaced by a novel lineage of sulfur-oxidizing bacteria only very distantly related to "Ca. Thiosymbion." Thus, this study highlights the remarkable plasticity of both animals and bacteria in establishing beneficial associations: the phallodriline hosts were able to acquire and maintain symbionts from two very different lineages of bacteria, while sulfur-oxidizing bacteria from two very distantly related lineages were able to independently establish symbiotic relationships with phallodriline hosts.

  • 310.
    Berglund, Ann-Charlotte
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Centrum för bioinformatik.
    Sjölund, Erik
    Östlund, Gabriel
    Sonnhammer, Erik L. L.
    InParanoid 6: eukaryotic ortholog clusters with inparalogs2008Ingår i: Nucleic Acids Research, ISSN 0305-1048, E-ISSN 1362-4962, Vol. 36, s. D263-D266Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The InParanoid eukaryotic ortholog database (http://InParanoid.sbc.su.se/) has been updated to version 6 and is now based on 35 species. We collected all available complete eukaryotic proteomes and Escherichia coli, and calculated ortholog groups for all 595 species pairs using the InParanoid program. This resulted in 2 642 187 pairwise ortholog groups in total. The orthology-based species relations are presented in an orthophylogram. InParanoid clusters contain one or more orthologs from each of the two species. Multiple orthologs in the same species, i.e. inparalogs, result from gene duplications after the species divergence. A new InParanoid website has been developed which is optimized for speed both for users and for updating the system. The XML output format has been improved for efficient processing of the InParanoid ortholog clusters.

  • 311.
    Berglund, Eva C.
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Molekylär evolution.
    Ellegaard, Kirsten
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Molekylär evolution.
    Granberg, Fredrik
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Molekylär evolution.
    Xie, Zhoupeng
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Molekylär evolution.
    Maruyama, Soichi
    Kosoy, Michael Y.
    Birtles, Richard J.
    Andersson, Siv G. E.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Molekylär evolution.
    Rapid diversification by recombination in Bartonella grahamii from wild rodents in Asia contrasts with low levels of genomic divergence in Northern Europe and America2010Ingår i: Molecular Ecology, ISSN 0962-1083, E-ISSN 1365-294X, Vol. 19, nr 11, s. 2241-2255Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Bartonella is a genus of vector-borne bacteria that infect the red blood cells of mammals, and includes several human-specific and zoonotic pathogens. Bartonella grahamii has a wide host range and is one of the most prevalent Bartonella species in wild rodents. We studied the population structure, genome content and genome plasticity of a collection of 26 B. grahamii isolates from 11 species of wild rodents in seven countries. We found strong geographic patterns, high recombination frequencies and large variations in genome size in B. grahamii compared with previously analysed cat- and human-associated Bartonella species. The extent of sequence divergence in B. grahamii populations was markedly lower in Europe and North America than in Asia, and several recombination events were predicted between the Asian strains. We discuss environmental and demographic factors that may underlie the observed differences.

  • 312. Berglund, Gunnar I.
    et al.
    Carlsson, Gunilla H.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Biologiska sektionen, Institutionen för cell- och molekylärbiologi.
    Smith, Andrew T.
    Szöke, Hanna
    Henriksen, Anette
    Hajdu, Janos
    The catalytic pathway of horseradish peroxidase at high resolution2002Ingår i: Nature, Vol. 417, s. 463-468Artikel i tidskrift (Refereegranskat)
  • 313.
    Berglund-Sonnhammer, Ann-Charlotte
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Centrum för bioinformatik.
    Steffansson, Pär
    Betts, Matthew J.
    Liberles, David A.
    Optimal gene trees from sequences and species trees using a soft interpretation of parsimony2006Ingår i: Journal of Molecular Evolution, ISSN 0022-2844, E-ISSN 1432-1432, Vol. 63, nr 2, s. 240-250Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Gene duplication and gene loss as well as other biological events can result in multiple copies of genes in a given species. Because of these gene duplication and loss dynamics, in addition to variation in sequence evolution and other sources of uncertainty, different gene trees ultimately present different evolutionary histories. All of this together results in gene trees that give different topologies from each other, making consensus species trees ambiguous in places. Other sources of data to generate species trees are also unable to provide completely resolved binary species trees. However, in addition to gene duplication events, speciation events have provided some underlying phylogenetic signal, enabling development of algorithms to characterize these processes. Therefore, a soft parsimony algorithm has been developed that enables the mapping of gene trees onto species trees and modification of uncertain or weakly supported branches based on minimizing the number of gene duplication and loss events implied by the tree. The algorithm also allows for rooting of unrooted trees and for removal of in-paralogues (lineage-specific duplicates and redundant sequences masquerading as such). The algorithm has also been made available for download as a software package, Softparsmap.

  • 314.
    Bergman, Ebba
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär evolution.
    Haplotype Inference as a caseof Maximum Satisfiability: A strategy for identifying multi-individualinversion points in computational phasing2017Självständigt arbete på avancerad nivå (yrkesexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
    Abstract [en]

    Phasing genotypes from sequence data is an important step betweendata gathering and downstream analysis in population genetics,disease studies, and multiple other fields. This determination ofthe sequences of markers corresponding to the individualchromosomes can be done on data where the markers are in lowdensity across the chromosome, such as from single nucleotidepolymorphism (SNP) microarrays, or on data with a higher localdensity of markers like in next generation sequencing (NGS). Thesorted markers may then be used for many different analyses anddata processing such as linkage analysis, or inference of missinggenotypes in the process of imputation

    cnF2freq is a haplotype phasing program that uses an uncommonapproach allowing it to divide big groups of related individualsinto smaller ones. It sets an initial haplotype phase and theniteratively changes it using estimations from Hidden MarkovModels. If a marker is judged to have been placed in the wronghaplotype, a switch needs to be made so that it belongs to thecorrect phase. The objective of this project was to go fromallowing only one individual within a group to be switched in aniteration to allowing multiple switches that are dependent on eachother.

    The result of this project is a theoretical solution for allowingmultiple dependent switches in cnF2freq, and an implementedsolution using the max-SAT solver toulbar2.

  • 315.
    Bergquist, Jonas
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för fysikalisk och analytisk kemi, Analytisk kemi.
    Håkansson, Per
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Jonfysik.
    Sundqvist, Bo
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Jonfysik.
    Zubarev, Roman
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi.
    Mass spectrometry of proteins - Uppsala perspectives on past and present: Paper in honor of Prof. Peter Roepstorff's 65th birthday2007Ingår i: International Journal of Mass Spectrometry, ISSN 1387-3806, E-ISSN 1873-2798, Vol. 268, nr 2-3, s. 73-82Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The development of biological mass spectrometry has been rapid in the past three to four decades. In particular, the possibility to detect and identify peptides and proteins from biologically and medically relevant samples has revolutionized life sciences. The development has gone from a stage where the detection of insulin in a mass spectrum was a major event to one in which the recording of mass spectra with more than 104 resolved and calibrating peaks in each spectrum is a routine task.

    In this paper, the evolution of protein mass spectrometry will be discussed from the Uppsala horizon with special emphasis on the unique coupling between ion induced desorption of biomolecules and ion track physics.

  • 316.
    Bergström, Joakim J. E.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Heyman, Birgitta
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Mikrobiologi.
    Mice Immunized With IgG Anti-Sheep Red Blood Cells (SRBC) Together With SRBC Have a Suppressed Anti-SRBC Antibody Response but Generate Germinal Centers and Anti-IgG Antibodies in Response to the Passively Administered IgG2017Ingår i: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 8, artikel-id 911Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Antigen-specific IgG antibodies, passively administered together with large particulate antigens such as erythrocytes, can completely suppress the antigen-specific antibody response. The mechanism behind has been elusive. Herein, we made the surprising observation that mice immunized with IgG anti-sheep red blood cells (SRBC) and SRBC, in spite of a severely suppressed anti-SRBC response, have a strong germinal center (GC) response. This occurred regardless of whether the passively administered IgG was of the same allotype as that of the recipient or not. Six days after immunization, the GC size and the number of GC B cells were higher in mice immunized with SRBC alone than in mice immunized with IgG and SRBC, but at the other time points these parameters were similar. GCs in the IgG-groups had a slight shift toward dark zone B cells 6 days after immunization and toward light zone B cells 10 days after immunization. The proportions of T follicular helper cells (TFH) and T follicular regulatory cells (TFR) were similar in the two groups. Interestingly, mice immunized with allogeneic IgG anti-SRBC together with SRBC mounted a vigorous antibody response against the passively administered suppressive IgG. Thus, although their anti-SRBC response was almost completely suppressed, an antibody response against allogeneic, and probably also syngeneic, IgG developed. This most likely explains the development of GCs in the absence of an anti-SRBC antibody response.

  • 317.
    Bergström Lind, Sara
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Artemenko, Konstantin A
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för fysikalisk och analytisk kemi, Analytisk kemi.
    Elfineh, Lioudmila
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Mayrhofer, Corina
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi.
    Zubarev, Roman A
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi.
    Bergquist, Jonas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Kemiska sektionen, Institutionen för fysikalisk och analytisk kemi, Analytisk kemi.
    Pettersson, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Toward a comprehensive characterization of the phosphotyrosine proteome2011Ingår i: Cellular Signalling, ISSN 0898-6568, E-ISSN 1873-3913, Vol. 23, nr 8, s. 1387-1395Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Tyrosine phosphorylation (pTyr) regulates important cell functions and plays a key role in carcinogenesis. The purpose of this study was to perform a comprehensive study of the phosphotyrosine proteome. Immunoaffinity enriched pTyr proteins and peptides from K562 leukemia cells were analyzed with high-resolving liquid chromatography mass spectrometry. Two different antibodies selective for the pTyr modification were used in repeated enrichments to identify as many pTyr peptides as possible. Stringent verification of putative pTyr sites was performed to assure high reliability in the subsequent biological interpretation of the data. Identified pTyr proteins were subjected to pathway analysis by using different analytical tools. In total, 294 pTyr peptides belonging to 217 pTyr proteins were identified, 15 of which had not previously been reported to be modified by pTyr. The pTyr proteins were clustered in six major groups based on the biological functions "cellular signaling", "cell motility and shape", "cell cycle process", "transport", "RNA processing" and "protein processing". The pTyr proteins were mainly positioned in the following cellular compartments: cytoplasm, cytoskeleton, nucleus and ribonucleoprotein complexes. An interesting finding was that many proteins were related to RNA processing and were found to be heterogeneous nuclear ribonucleoproteins. Also, more than half of the novel pTyr proteins were localized to the nucleus, of which three (PBX2, TEAD1 and DIDO1) were classified as transcription factors and two (CENPC1 and MAD2L1) are associated with cell division control.

  • 318.
    Bergström Lind, Sara
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Molin, Magnus
    Savitski, Mikhail M.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi.
    Emilsson, Lina
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Åström, Jonas
    Uppsala BIO.
    Hedberg, Ludwig
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Adams, Chris
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi.
    Nielsen, Michael
    Engström, Åke
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Elfineh, Lioudmila
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Andersson, Eva
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Zubarev, Roman
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi.
    Pettersson, Ulf
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för genetik och patologi.
    Immunoaffinity Enrichments Followed by Mass Spectrometric Detection for Studying Global Protein Tyrosine Phosphorylation2008Ingår i: Journal of Proteome Research, ISSN 1535-3893, E-ISSN 1535-3907, Vol. 7, nr 7, s. 2897-2910Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Phosphorylation of protein tyrosine residues regulates important cell functions and is, when dysregulated, often crucially involved in oncogenesis. It is therefore important to develop and evaluate methods for identifying and studying tyrosine phosphorylated (P-Tyr) proteins. P-Tyr proteins are present at very low concentrations within cells, requiring highly selective enrichment methods to be detected. In this study, we applied immunoaffinity as enrichment step for P-Tyr proteins. Five selected anti-phosphotyrosine antibodies (monoclonal antibodies 4G10, PY100, PYKD1, 13F9 and one polyclonal antiserum) were evaluated with respect to their capability to enrich P-Tyr proteins from cell extracts of the K562 leukemia cell line. The enrichment resulted in the detection of a group of proteins that potentially were tyrosine-phosphorylated (putative P-Tyr proteins). High accuracy identification of actual P-Tyr sites were performed using a highly selective and sensitive liquid chromatography Fourier transform mass spectrometer (LC-FTMS) setup with complementary collision activated dissociation (CAD) and electron capture dissociation (ECD) fragmentations. 4G10 and PY100 antibodies recognized the greatest number of putative P-Tyr proteins in initial screening experiments and were therefore further evaluated and compared in immunoaffinity enrichment of both P-Tyr proteins and peptides. Using the 4G10 antibody for enrichment of proteins, we identified 459 putative P-Tyr proteins by MS. Out of these proteins, 12 were directly verified as P-Tyr proteins by MS analysis of the actual site. Using the PY100 antibody for enrichment of peptides, we detected 67 P-Tyr peptides (sites) and 89 putative P-Tyr proteins. Generally, enrichment at the peptide level made it difficult to reliably determine the identity of the proteins. In contrast, protein identification following immunoaffinity enrichment at the protein level gave greater sequence coverage and thus a higher confidence in the protein identification. By combining all available information, 40 proteins were identified as true P-Tyr proteins from the K562 cell line. In conclusion, this study showed that a combination of immunoaffinity enrichment using multiple antibodies of both intact and digested proteins in parallel experiments is required for best possible coverage of all possible P-Tyr proteins in a sample.

  • 319.
    Bergström, Rosita
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär cellbiologi.
    Epigenetic Regulation of Replication Timing and Signal Transduction2008Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Upon fertilization the paternal and maternal genomes unite, giving rise to the embryo, with its unique genetic code. All cells in the human body are derived from the fertilized ovum: hence they all contain (with a few exceptions) the same genetic composition. However, by selective processes, genes are turned on and off in an adaptable, and cell type-specific, manner. The aim of this thesis is to investigate how signals coming from outside the cell and epigenetic factors residing in the cell nucleus, cooperate to control gene expression.

    The transforming growth factor-β (TGF-β) superfamily consists of around 30 cytokines, which are essential for accurate gene regulation during embryonic development and adult life. Among these are the ligands TGF-β1 and bone morphogenetic (BMP) -7, which interact with diverse plasma membrane receptors, but signal via partly the same Smad proteins. Smad4 is essential to achieve TGF-β-dependent responses. We observed that by regulating transcription factors such as Id2 and Id3 in a specific manner, TGF-β1 and BMP-7 achieve distinct physiological responses.

    Moreover, we demonstrate that CTCF, an insulator protein regulating higher order chromatin conformation, is able to direct transcription by recruiting RNA polymerase II to its target sites. This is the first mechanistic explanation of how an insulator protein can direct transcription, and reveals a link between epigenetic modifications and classical regulators of transcription. We also detected that DNA loci occupied by CTCF replicate late. The timing of replication is a crucial determinant of gene activity. Genes replicating early tend to be active, whereas genes replicating late often are silenced. Thus, CTCF can regulate transcription at several levels. Finally, we detected a substantial cross-talk between CTCF and TGF-β signaling. This is the first time that a direct interplay between a signal transduction pathway and the chromatin insulator CTCF is demonstrated.

    Delarbeten
    1. Id2 and Id3 Define the Potency of Cell Proliferation and Differentiation Responses to Transforming Growth Factor β and Bone Morphogeenetic Protein
    Öppna denna publikation i ny flik eller fönster >>Id2 and Id3 Define the Potency of Cell Proliferation and Differentiation Responses to Transforming Growth Factor β and Bone Morphogeenetic Protein
    Visa övriga...
    2004 (Engelska)Ingår i: Molecular Cell Biology, Vol. 24, nr 10, s. 4241-54Artikel i tidskrift (Refereegranskat) Published
    Identifikatorer
    urn:nbn:se:uu:diva-96649 (URN)
    Tillgänglig från: 2008-01-25 Skapad: 2008-01-25 Senast uppdaterad: 2009-03-26Bibliografiskt granskad
    2. CTCF Interacts with and Recruits the Largest Subunit of RNA Polymerase II to CTCF Target Sites Genome-Wide
    Öppna denna publikation i ny flik eller fönster >>CTCF Interacts with and Recruits the Largest Subunit of RNA Polymerase II to CTCF Target Sites Genome-Wide
    Visa övriga...
    2007 (Engelska)Ingår i: Molecular and Cellular Biology, ISSN 0270-7306, E-ISSN 1098-5549, Vol. 27, nr 5, s. 1631-1648Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    CTCF is a transcription factor with highly versatile functions ranging from gene activation and repression to the regulation of insulator function and imprinting. Although many of these functions rely on CTCF-DNA interactions, it is an emerging realization that CTCF-dependent molecular processes involve CTCF interactions with other proteins. In this study, we report the association of a subpopulation of CTCF with the RNA polymerase II (Pol II) protein complex. We identified the largest subunit of Pol II (LS Pol II) as a protein significantly colocalizing with CTCF in the nucleus and specifically interacting with CTCF in vivo and in vitro. The role of CTCF as a link between DNA and LS Pol II has been reinforced by the observation that the association of LS Pol II with CTCF target sites in vivo depends on intact CTCF binding sequences. "Serial" chromatin immunoprecipitation (ChIP) analysis revealed that both CTCF and LS Pol II were present at the β-globin insulator in proliferating HD3 cells but not in differentiated globin synthesizing HD3 cells. Further, a single wild-type CTCF target site (N-Myc-CTCF), but not the mutant site deficient for CTCF binding, was sufficient to activate the transcription from the promoterless reporter gene in stably transfected cells. Finally, a ChIP-on-ChIP hybridization assay using microarrays of a library of CTCF target sites revealed that many intergenic CTCF target sequences interacted with both CTCF and LS Pol II. We discuss the possible implications of our observations with respect to plausible mechanisms of transcriptional regulation via a CTCF-mediated direct link of LS Pol II to the DNA.

    Nationell ämneskategori
    Biologiska vetenskaper
    Identifikatorer
    urn:nbn:se:uu:diva-96650 (URN)10.1128/MCB.01993-06 (DOI)000244305500008 ()17210645 (PubMedID)
    Tillgänglig från: 2008-01-25 Skapad: 2008-01-25 Senast uppdaterad: 2017-12-14Bibliografiskt granskad
    3. CTCF Regulates Asynchronous Replication of the Imprinted H19/Igf2 Domain
    Öppna denna publikation i ny flik eller fönster >>CTCF Regulates Asynchronous Replication of the Imprinted H19/Igf2 Domain
    2007 (Engelska)Ingår i: Cell Cycle, ISSN 1538-4101, E-ISSN 1551-4005, Vol. 6, nr 4, s. 450-454Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    Asynchronous replication during S phase is a universal characteristic of genomically imprinted genes. Replication timing in imprinted domains is determined epigenetically, as it is parent of origin specific, and is seen in the absence of sequence divergence between the two alleles. At the imprinted H19/lgf2 domain, the methylated paternal allele replicates early while the CTCF-bound maternal allele replicates late during S phase. CTCF regulates the allele-specific epigenetic characteristics of this domain, including methylation, transcription and chromosome conformation. Here we show that maternal, but not paternal inheritance of a mutated H19 imprinting control region, lacking functional CTCF binding sites, underlies a late to early switch in replication timing of the maternal H19/ lgf2 domain.

    Nyckelord
    replication timing, CTCF, H19/Igf2, genomic imprinting
    Nationell ämneskategori
    Biologiska vetenskaper
    Identifikatorer
    urn:nbn:se:uu:diva-96651 (URN)000245495600013 ()17329968 (PubMedID)
    Tillgänglig från: 2008-01-25 Skapad: 2008-01-25 Senast uppdaterad: 2017-12-14Bibliografiskt granskad
    4. CTCF and Smad Proteins of the TGF-β Pathway interact during regulation of gene expression from the H19 imprinted control region
    Öppna denna publikation i ny flik eller fönster >>CTCF and Smad Proteins of the TGF-β Pathway interact during regulation of gene expression from the H19 imprinted control region
    Visa övriga...
    (Engelska)Manuskript (Övrig (populärvetenskap, debatt, mm))
    Identifikatorer
    urn:nbn:se:uu:diva-96652 (URN)
    Tillgänglig från: 2008-01-25 Skapad: 2008-01-25 Senast uppdaterad: 2010-01-14Bibliografiskt granskad
  • 320.
    Bergström, Rosita
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär cellbiologi.
    Morén, Anita
    Guibert, Sylvain
    Heldin, Carl-Henrik
    Ohlsson, Rolf
    Moustakas, Aristidis
    CTCF and Smad Proteins of the TGF-β Pathway interact during regulation of gene expression from the H19 imprinted control regionManuskript (Övrig (populärvetenskap, debatt, mm))
  • 321.
    Bernander, R
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Biologiska sektionen, Institutionen för cell- och molekylärbiologi.
    Chromosome replication, nucleoid segregation and cell division in Archaea2000Ingår i: TRENDS IN MICROBIOLOGY, Vol. 8, nr 6, s. 278-283Artikel, recension (Övrigt vetenskapligt)
    Abstract [en]

    Recent progress in cell cycle analysis of archaea has included the identification of putative chromosome replication origins, novel DNA polymerases and an unusual mode of cell cycle organization featuring multiple copies of the chromosome and asymmetric c

  • 322.
    Bernander, R
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Biologiska sektionen, Institutionen för cell- och molekylärbiologi.
    Poplawski, A
    Grogan, DW
    Altered patterns of cellular growth, morphology, replication and division in conditional-lethal mutants of the thermophilic archaeon Sulfolobus acidocaldarius2000Ingår i: MICROBIOLOGY-UK, ISSN 1350-0872, Vol. 146, s. 749-757Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    As a basis for studing the essential cellular processes of hyperthermophilic archaea. thermosensitive mutants of Sulfolobus acidocaldarius were isolated and characterized. Exponential-phase liquid cultures were shifted to the nonpermissive temperature and

  • 323.
    Bernander, R
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Biologiska sektionen, Institutionen för cell- och molekylärbiologi.
    Skarstad, K
    Mapping of a chromosome replication origin in an archaeon2000Ingår i: TRENDS IN MICROBIOLOGY, Vol. 8, nr 12, s. 535-537Övrigt (Övrigt vetenskapligt)
  • 324.
    Bernander, Rolf
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Molekylär evolution.
    Ettema, Thijs J.G.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för organismbiologi, Molekylär evolution.
    FtsZ-less cell division in archaea and bacteria2010Ingår i: Current Opinion in Microbiology, ISSN 1369-5274, E-ISSN 1879-0364, Vol. 13, nr 6, s. 747-752Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A dedicated cell division machinery is needed for efficient proliferation of an organism. The eukaryotic actin-myosin based mechanism and the bacterial FtsZ-dependent machinery have both been characterized in detail, and a third division mechanism, the Cdv system, was recently discovered in archaea from the Crenarchaeota phylum. Despite these findings, division mechanisms remain to be identified in, for example, organisms belonging to the bacterial PVC superphylum, bacteria with extremely reduced genomes, wall-less archaea and bacteria, and in archaea that carry out the division process without cell constriction. Cytokinesis mechanisms in these clades and individual taxa are likely to include adaptation of host functions to division of bacterial symbionts, transfer of bacterial division genes into the host genome, vesicle formation without a dedicated constriction machinery, cross-wall formation without invagination, as well as entirely novel division mechanisms.

  • 325. Bernander, Rolf
    et al.
    Lind, Anders E
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi.
    Ettema, Thijs J G
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi.
    An archaeal origin for the actin cytoskeleton: Implications for eukaryogenesis.2011Ingår i: Communicative & Integrative Biology, ISSN 1942-0889, E-ISSN 1942-0889, Vol. 4, nr 6, s. 664-7Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A hallmark of the eukaryotic cell is the actin cytoskeleton, involved in a wide array of processes ranging from shape determination and phagocytosis to intracellular transport and cytokinesis. Recently, we reported the discovery of an actin-based cytoskeleton also in Archaea. The archaeal actin ortholog, Crenactin, was shown to belong to a conserved operon, Arcade (actin-related cytoskeleton in Archaea involved in shape determination), encoding an additional set of cytoskeleton-associated proteins. Here, we elaborate on the implications of these findings for the evolutionary relation between archaea and eukaryotes, with particular focus on the possibility that eukaryotic actin and actin-related proteins have evolved from an ancestral archaeal actin gene. Archaeal actin could thus have played an important role in cellular processes essential for the origin and early evolution of the eukaryotic lineage. Further exploration of uncharacterized archaeal lineages is necessary to find additional missing pieces in the evolutionary trajectory that ultimately gave rise to present-day organisms.

  • 326.
    Bernander, Rolf
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär evolution.
    Lind, Anders E.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär evolution.
    Ettema, Thijs J.G.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär evolution.
    An archaeal origin for the actin cytoskeleton: implications for eukaryogenesis2011Ingår i: Communicative & Integrative Biology, ISSN 1942-0889, E-ISSN 1942-0889, Vol. 4, nr 6, s. 664-667Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A hallmark of the eukaryotic cell is the actin cytoskeleton, involved in a wide array of processes ranging from shape determination and phagocytosis to intracellular transport and cytokinesis. Recently, we reported the discovery of an actin-based cytoskeleton also in Archaea. The archaeal actin ortholog, Crenactin, was shown to belong to a conserved operon, Arcade (actin-related cytoskeleton in Archaea involved in shape determination), encoding an additional set of cytoskeleton-associated proteins. Here, we elaborate on the implications of these findings for the evolutionary relation between archaea and eukaryotes, with particular focus on the possibility that eukaryotic actin and actin-related proteins have evolved from an ancestral archaeal actin gene. Archaeal actin could thus have played an important role in cellular processes essential for the origin and early evolution of the eukaryotic lineage. Further exploration of uncharacterized archaeal lineages is necessary to find additional missing pieces in the evolutionary trajectory that ultimately gave rise to present-day organisms.

  • 327.
    Bernander, Rolf
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för evolution, genomik och systematik, Molekylär evolution.
    Lundgren, Magnus
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för evolution, genomik och systematik, Molekylär evolution. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Mikrobiologi.
    Ettema, Thijs J. G.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för evolution, genomik och systematik, Molekylär evolution.
    Comparative and functional analysis of the archaeal cell cycle2010Ingår i: Cell Cycle, ISSN 1538-4101, E-ISSN 1551-4005, Vol. 9, nr 4, s. 795-806Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The temporal and spatial organization of the chromosome replication, genome segregation and cell division processes is less well understood in species belonging to the Archaea, than in those from the Bacteria and Eukarya domains. Novel insights into the regulation and key components of the Sulfolobus acidocaldarius cell cycle have been obtained through genome-wide analysis of cell cycle-specific gene expression, followed by cloning and characterization of gene products expressed at different cell cycle stages. Here, the results of the transcript profiling are further explored, and potential key players in archaeal cell cycle progression are highlighted in an evolutionary context, by comparing gene expression patterns and gene conservation between three selected microbial species from different domains of life. We draw attention to novel putative nucleases and helicases implicated in DNA replication, recombination and repair, as well as to potential genome segregation factors. Focus is also placed upon regulatory features, including transcription factors and protein kinases inferred to be involved in the execution of specific cell cycle stages, and regulation through metabolic coupling is discussed.

  • 328.
    Besnier, Francois
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Centrum för bioinformatik.
    Development of Variance Component Methods for Genetic Dissection of Complex Traits2009Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    This thesis presents several developments on Variance component (VC) approach for Quantitative Trait Locus (QTL) mapping.

    The first part consists of methodological improvements: a new fast and efficient method for estimating IBD matrices, have been developed. The new method makes a better use of the computer resources in terms of computational power and storage memory, facilitating further improvements by resolving methodological bottlenecks in algorithms to scan multiple QTL. A new VC model have also been developed in order to consider and evaluate the correlation of the allelic effects within parental lines origin in experimental outbred crosses. The method was tested on simulated and experimental data and revealed a higher or similar power to detect QTL than linear regression based QTL mapping.

    The second part focused on the prospect to analyze multi-generational pedigrees by VC approach. The IBD estimation algorithm was extended to include haplotype information in addition to genotype and pedigree to improve the accuracy of the IBD estimates, and a new haplotyping algorithm was developed for limiting the risk of haplotyping errors in multigenerational pedigrees. Those newly developed methods where subsequently applied for the analysis of a nine generations AIL pedigree obtained after crossing two chicken lines divergently selected for body weight. Nine QTL described in a F2 population were replicated in the AIL pedigree, and our strategy to use both genotype and phenotype information from all individuals in the entire pedigree clearly made efficient use of the available genotype information provided in AIL.

    Delarbeten
    1. An Improved Method for Quantitative Trait Loci Detection and Identification of Within-Line Segregation in F2 Intercross Designs
    Öppna denna publikation i ny flik eller fönster >>An Improved Method for Quantitative Trait Loci Detection and Identification of Within-Line Segregation in F2 Intercross Designs
    2008 (Engelska)Ingår i: Genetics, ISSN 0016-6731, E-ISSN 1943-2631, Vol. 178, nr 4, s. 2315-2326Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    We present a new flexible, simple, and power ful genome-scan method (flexible intercross analysis, FIA) for detecting quantitative trait loci (QTL) in experimental line crosses. The method is based on a pure random-effects model that simultaneously models between- and within-line QTL variation for single as well as epistatic QTL. It utilizes the score statistic and thereby facilitates computationally efficient significance testing based on empirical significance thresholds obtained by means of permutations. The properties of the method are explored using simulations and analyses of experimental data. The simulations showed that the power of FIA was as good as, or better than, Haley–Knott regression and that FIA was rather insensitive to the level of allelic fixation in the founders, especially for pedigrees with few founders. A chromosome scan was conducted for a meat quality trait in an F2 intercross in pigs where a mutation in the halothane (Ryanodine receptor, RYR1) gene with a large effect on meat quality was known to segregate in one founder line. FIA obtained significant support for the halothane-associated QTL and identified the base generation allele with the mutated allele. A genome scan was also performed in a previously analyzed chicken F2 intercross. In the chicken intercross analysis, four previously detected QTL were confirmed at a 5% genomewide significance level, and FIA gave strong evidence (P , 0.01) for two of these QTL to be segregating within the founder lines. FIA was also extended to account for epistasis and using simulations we show that the method provides good estimates of epistatic QTL variance even for segregating QTL. Extensions of FIA and its applications on other intercross populations including backcrosses, advanced intercross lines, and heterogeneous stocks are also discussed.

    Nationell ämneskategori
    Genetik
    Forskningsämne
    Genetik
    Identifikatorer
    urn:nbn:se:uu:diva-101358 (URN)10.1534/genetics.107.083162 (DOI)000255239600039 ()18430952 (PubMedID)
    Tillgänglig från: 2009-05-06 Skapad: 2009-04-23 Senast uppdaterad: 2017-12-13Bibliografiskt granskad
    2. Fine mapping and replication of QTL in outbred chicken advanced intercross lines
    Öppna denna publikation i ny flik eller fönster >>Fine mapping and replication of QTL in outbred chicken advanced intercross lines
    Visa övriga...
    2011 (Engelska)Ingår i: Genetics Selection Evolution, ISSN 0999-193X, E-ISSN 1297-9686, Vol. 43, s. 3-Artikel i tidskrift (Refereegranskat) Published
    Abstract [en]

    BACKGROUND: Linkage mapping is used to identify genomic regions affecting the expression of complex traits. However, when experimental crosses such as F2 populations or backcrosses are used to map regions containing a Quantitative Trait Locus (QTL), the size of the regions identified remains quite large, i.e. 10 or more Mb. Thus, other experimental strategies are needed to refine the QTL locations. Advanced Intercross Lines (AIL) are produced by repeated intercrossing of F2 animals and successive generations, which decrease linkage disequilibrium in a controlled manner. Although this approach is seen as promising, both to replicate QTL analyses and fine-map QTL, only a few AIL datasets, all originating from inbred founders, have been reported in the literature.

    METHODS: We have produced a nine-generation AIL pedigree (n = 1529) from two outbred chicken lines divergently selected for body weight at eight weeks of age. All animals were weighed at eight weeks of age and genotyped for SNP located in nine genomic regions where significant or suggestive QTL had previously been detected in the F2 population. In parallel, we have developed a novel strategy to analyse the data that uses both genotype and pedigree information of all AIL individuals to replicate the detection of and fine-map QTL affecting juvenile body weight.

    RESULTS: Five of the nine QTL detected with the original F2 population were confirmed and fine-mapped with the AIL, while for the remaining four, only suggestive evidence of their existence was obtained. All original QTL were confirmed as a single locus, except for one, which split into two linked QTL.

    CONCLUSIONS: Our results indicate that many of the QTL, which are genome-wide significant or suggestive in the analyses of large intercross populations, are true effects that can be replicated and fine-mapped using AIL. Key factors for success are the use of large populations and powerful statistical tools. Moreover, we believe that the statistical methods we have developed to efficiently study outbred AIL populations will increase the number of organisms for which in-depth complex traits can be analyzed.

     

    Nationell ämneskategori
    Genetik
    Forskningsämne
    Genetik
    Identifikatorer
    urn:nbn:se:uu:diva-101398 (URN)10.1186/1297-9686-43-3 (DOI)000287133300001 ()21241486 (PubMedID)
    Tillgänglig från: 2009-04-24 Skapad: 2009-04-24 Senast uppdaterad: 2017-12-13
    3.
    Posten kunde inte hittas. Det kan bero på att posten inte längre är tillgänglig eller att du har råkat ange ett felaktigt id i adressfältet.