uu.seUppsala universitets publikasjoner
Endre søk
Begrens søket
1234567 1 - 50 of 3232
RefereraExporteraLink til resultatlisten
Permanent link
Referera
Referensformat
  • apa
  • ieee
  • modern-language-association
  • vancouver
  • Annet format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annet språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Treff pr side
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sortering
  • Standard (Relevans)
  • Forfatter A-Ø
  • Forfatter Ø-A
  • Tittel A-Ø
  • Tittel Ø-A
  • Type publikasjon A-Ø
  • Type publikasjon Ø-A
  • Eldste først
  • Nyeste først
  • Skapad (Eldste først)
  • Skapad (Nyeste først)
  • Senast uppdaterad (Eldste først)
  • Senast uppdaterad (Nyeste først)
  • Disputationsdatum (tidligste først)
  • Disputationsdatum (siste først)
  • Standard (Relevans)
  • Forfatter A-Ø
  • Forfatter Ø-A
  • Tittel A-Ø
  • Tittel Ø-A
  • Type publikasjon A-Ø
  • Type publikasjon Ø-A
  • Eldste først
  • Nyeste først
  • Skapad (Eldste først)
  • Skapad (Nyeste først)
  • Senast uppdaterad (Eldste først)
  • Senast uppdaterad (Nyeste først)
  • Disputationsdatum (tidligste først)
  • Disputationsdatum (siste først)
Merk
Maxantalet träffar du kan exportera från sökgränssnittet är 250. Vid större uttag använd dig av utsökningar.
  • 1.
    Abdeldaim, Guma M. K.
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk bakteriologi.
    Strålin, Kristoffer
    Department of Infectious Diseases, Örebro University Hospital.
    Kirsebom, Leif A.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Mikrobiologi.
    Olcén, Per
    Department of Clinical Microbiology, Örebro University Hospital.
    Blomberg, Jonas
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk virologi.
    Herrmann, Björn
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Klinisk bakteriologi.
    Detection of Haemophilus influenzae in respiratory secretions from pneumonia patients by quantitative real-time polymerase chain reaction2009Inngår i: Diagnostic microbiology and infectious disease, ISSN 0732-8893, E-ISSN 1879-0070, Vol. 64, nr 4, s. 366-373Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A quantitative real-time polymerase chain reaction (PCR) based on the omp P6 gene was developed to detect Haemophilus influenzae. Its specificity was determined by analysis of 29 strains of 11 different Haemophilus spp. and was compared with PCR assays having other target genes: rnpB, 16S rRNA, and bexA. The method was evaluated on nasopharyngeal aspirates from 166 adult patients with community-acquired pneumonia. When 104 DNA copies/mL was used as cutoff limit for the method, P6 PCR had a sensitivity of 97.5% and a specificity of 96.0% compared with the culture. Of 20 culture-negative but P6 PCR-positive cases, 18 were confirmed by fucK PCR as H. influenzae. Five (5.9%) of 84 nasopharyngeal aspirates from adult controls tested PCR positive. We conclude that the P6 real-time PCR is both sensitive and specific for identification of H. influenzae in respiratory secretions. Quantification facilitates discrimination between disease-causing H. influenzae strains and commensal colonization.

  • 2. Abola, EE
    et al.
    Bairoch, A
    Barker, WC
    Beck, S
    Benson, DA
    Berman, H
    Cantor, C
    Cantor, C
    Doubet, S
    Hubbard, TJP
    Jones, T. A.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Biologiska sektionen, Institutionen för cell- och molekylärbiologi. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Strukturell molekylärbiologi.
    Kleywegt, G J
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Biologiska sektionen, Institutionen för cell- och molekylärbiologi. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Strukturell molekylärbiologi.
    Kolaskar, AS
    van Kuik, A
    Lesk, A M
    Mewes, H W
    Neuhaus, D
    Pfeiffer, F
    Ten Eyck, LF
    Simpson, RJ
    Stoesser, G
    Sussman, J L
    Tateno, Y
    Tsugita, A
    Ulrich, EL
    Vliegenthart, JFG
    Quality control in databanks for molecular biology2000Inngår i: BioEssays, Vol. 22, s. 1024-1034Artikkel, forskningsoversikt (Annet (populærvitenskap, debatt, mm))
  • 3.
    Acharya, P
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Biologiska sektionen, Institutionen för bioorganisk kemi. Institutionen för cell- och molekylärbiologi, Bioorganisk kemi.
    Chattopadhyaya, J
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Biologiska sektionen, Institutionen för bioorganisk kemi. Institutionen för cell- och molekylärbiologi, Bioorganisk kemi.
    Electrostatic Cross-modulation of the Pseudoaromatic Character in Single Stranded RNA by Nearest-neighbor interactions2005Inngår i: Pure and Applied Chemistry, Vol. 77, nr 1, s. 291-311Artikkel i tidsskrift (Fagfellevurdert)
  • 4. Adamczyk, Andrew J.
    et al.
    Cao, Jie
    Kamerlin, Shina C. Lynn
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Beräknings- och systembiologi.
    Warshel, Arieh
    Catalysis by dihydrofolate reductase and other enzymes arises from electrostatic preorganization, not conformational motions2011Inngår i: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 108, nr 34, s. 14115-14120Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The proposal that enzymatic catalysis is due to conformational fluctuations has been previously promoted by means of indirect considerations. However, recent works have focused on cases where the relevant motions have components toward distinct conformational regions, whose population could be manipulated by mutations. In particular, a recent work has claimed to provide direct experimental evidence for a dynamical contribution to catalysis in dihydrofolate reductase, where blocking a relevant conformational coordinate was related to the suppression of the motion toward the occluded conformation. The present work utilizes computer simulations to elucidate the true molecular basis for the experimentally observed effect. We start by reproducing the trend in the measured change in catalysis upon mutations (which was assumed to arise as a result of a "dynamical knockout" caused by the mutations). This analysis is performed by calculating the change in the corresponding activation barriers without the need to invoke dynamical effects. We then generate the catalytic landscape of the enzyme and demonstrate that motions in the conformational space do not help drive catalysis. We also discuss the role of flexibility and conformational dynamics in catalysis, once again demonstrating that their role is negligible and that the largest contribution to catalysis arises from electrostatic preorganization. Finally, we point out that the changes in the reaction potential surface modify the reorganization free energy (which includes entropic effects), and such changes in the surface also alter the corresponding motion. However, this motion is never the reason for catalysis, but rather simply a reflection of the shape of the reaction potential surface.

  • 5.
    Adams, Christopher
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper.
    Kjeldsen, Frank
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Tekniska sektionen, Institutionen för teknikvetenskaper, Jonfysik.
    Patriksson, Alexandra
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi.
    van Der Spoel, David
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär biofysik.
    Gräslund, Astrid
    Papadopolous, Evangelos
    Zubarev, Roman
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi.
    Probing Solution-Phase and Gas-Phase Structures of Trp-cage Cations by Chiral Substitution and Spectroscopic Techniques2006Inngår i: International Journal of Mass Spectrometry, ISSN 1387-3806, E-ISSN 1873-2798, Vol. 253, nr 3, s. 263-273Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The relevance of gas-phase protein structure to its solution structure is of the utmost importance in studying biomolecules by mass spectrometry. D-Amino acid substitutions within a minimal protein. Trp-cage. were used to correlate solution-phase properties as measured by circular dichroism with solution/gas-phase conformational features of protein cations probed via charge state distribution (CSD) in electrospray ionization. and gas-phase features revealed by tandem mass spectrometry (MS/MS). The gas-phase features were additionally supported by force-field molecular dynamics simulations. CD data showed that almost any single-residue D-substitution destroys the most prominent CD feature of the "native" all-L isomer, alpha-helicity. CSD was able to qualitatively assess the degree of compactness of solution-phase molecular structures. CSD results were consistent with the all-L form being the most compact in solution among all studied stereoisomers except for the D-Asn(1) isomer. D-substitutions of the aromatic Y(3), W(6) and Q(5) residues generated the largest deviations in CSD data among single amino acid substitutions. consistent with the critical role of these residues in Trp-cage stability. Electron capture dissociation of the stereoisomer dications gave an indication that some gas-phase structural features of Trp-cage are similar to those in solution. This result is supported by MDS data oil five of the studied stereoisomer dications in the gas-phase. The MDS-derived minimum-energy structures possessed more extensive hydrogen bonding than the solution-phase structure of the native form, deviating from the latter by 3-4 angstrom and were not 'inside-out' compared to native structures. MDS data could be correlated with CD data and even with ECD results. which aided in providing a long-range structural constraint for MDS. The overall conclusion is the general resemblance, despite the difference on the detailed level, of the preferred structures in both phases for the mini protein Trp-cage.

  • 6.
    Adler, Marlen
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Anjum, Mehreen
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Berg, Otto, G.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Beräknings- och systembiologi.
    Andersson, Dan I.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Sandegren, Linus
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    High Fitness Costs and Instability of Gene Duplications Reduce Rates of Evolution of New Genes by Duplication-Divergence Mechanisms2014Inngår i: Molecular biology and evolution, ISSN 0737-4038, E-ISSN 1537-1719, Vol. 31, nr 6, s. 1526-1535Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [sv]

    An important mechanism for generation of new genes is by duplication-divergence of existing genes. Duplication-divergence includes several different sub-models, such as subfunctionalization where after accumulation of neutral mutations the original function is distributed between two partially functional and complementary genes, and neofunctionalization where a new function evolves in one of the duplicated copies while the old function is maintained in another copy. The likelihood of these mechanisms depends on the longevity of the duplicated state, which in turn depends on the fitness cost and genetic stability of the duplications. Here, we determined the fitness cost and stability of defined gene duplications/amplifications on a low copy number plasmid. Our experimental results show that the costs of carrying extra gene copies are substantial and that each additional kbp of DNA reduces fitness by approximately 0.15%. Furthermore, gene amplifications are highly unstable and rapidly segregate to lower copy numbers in absence of selection. Mathematical modelling shows that the fitness costs and instability strongly reduces the likelihood of both sub- and neofunctionalization, but that these effects can be off-set by positive selection for novel beneficial functions.

  • 7.
    Adler, Sara
    et al.
    Umea Univ, Unit Clin Res Ctr Ostersund, Dept Publ Hlth & Clin Med, Umea, Sweden..
    Widerstrom, Micael
    Umea Univ, Unit Communicable Dis Control & Prevent Ostersund, Dept Clin Microbiol, Umea, Sweden..
    Lindh, Johan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Mikrobiologi.
    Lilja, Mikael
    Umea Univ, Unit Clin Res Ctr Ostersund, Dept Publ Hlth & Clin Med, Umea, Sweden..
    Symptoms and risk factors of Cryptosporidium hominis infection in children: data from a large waterborne outbreak in Sweden2017Inngår i: Parasitology Research, ISSN 0932-0113, E-ISSN 1432-1955, Vol. 116, nr 10, s. 2613-2618Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Cryptosporidium is a major cause of diarrheal disease worldwide. In developing countries, this infection is endemic and in children, associated with growth faltering and cognitive function deficits, with the most severe impact on those aged <2 years. Little has been reported about symptoms and risk factors for children in industrialized countries, although the disease incidence is increasing in such regions. In November 2010, a large waterborne outbreak of C. hominis occurred in the city of Ostersund in Sweden. Approximately 27,000 of the 60,000 inhabitants were symptomatic. We aimed to describe duration of symptoms and the risk factors for infection with C. hominis in children aged <15 years in a Western setting. Within 2 months after a boil water advisory, a questionnaire was sent to randomly selected inhabitants of all ages, including 753 children aged <15 years. Those with >= 3 loose stools/day were defined as cases of diarrhoea. The response rate was 70.3%, and 211 children (39.9%) fulfilled the case definition. Mean duration of diarrhoea was 7.5 days (median 6, range 1-80 days). Recurrence, defined as a new episode of diarrhoea after >= 2 days of normal stools, occurred in 52.5% of the cases. Significant risk factors for infection, besides living within the distribution area of the contaminated water plant, included a high level of water consumption, male sex, and a previous history of loose stools. The outbreak was characterized by high attack and recurrence rates, emphasizing the necessity of water surveillance to prevent future outbreaks.

  • 8.
    Aguileta, Gabriela
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Centrum för bioinformatik.
    Bielawski, Joseph P.
    Yang, Ziheng
    Proposed standard nomenclature for the alpha- and beta-globin gene families2006Inngår i: Genes & Genetic Systems, ISSN 1341-7568, E-ISSN 1880-5779, Vol. 81, nr 5, s. 367-371Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The globin family of genes and proteins has been a recurrent object of study for many decades. This interest has generated a vast amount of knowledge. However it has also created an inconsistent and confusing nomenclature, due to the lack of a systematic approach to naming genes and failure to reflect the phylogenetic relationships among genes of the gene family. To alleviate the problems with the existing system, here we propose a standardized nomenclature for the alpha and beta globin family of genes, based on a phylogenetic analysis of vertebrate alpha and beta globins, and following the Guidelines for Human Gene Nomenclature.

  • 9.
    Agullo, Luis
    et al.
    Univ Vic Cent Univ Catalonia UVIC UCC, Dept Syst Biol, U Sci Tech, Sagrada Familia 7, Vic 08500, Spain..
    Buch, Ignasi
    Hosp Del Mar Med Res Inst IMIM, Computat Biophys Lab, Barcelona 08003, Spain..
    Gutierrez-de-Teran, Hugo
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Beräkningsbiologi och bioinformatik.
    Garcia-Dorado, David
    Vall DHebron Res Inst VHIR, Cardiocirculatory Pathol Grp, Barcelona 08035, Spain..
    Villa-Freixa, Jordi
    Univ Vic Cent Univ Catalonia UVIC UCC, Dept Syst Biol, U Sci Tech, Sagrada Familia 7, Vic 08500, Spain..
    Computational exploration of the binding mode of heme-dependent stimulators into the active catalytic domain of soluble guanylate cyclase2016Inngår i: Proteins: Structure, Function, and Bioinformatics, ISSN 0887-3585, E-ISSN 1097-0134, Vol. 84, nr 10, s. 1534-1548Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Soluble guanylate cyclase (sGC), the main target of nitric oxide (NO), has been proven to have a significant role in coronary artery disease, pulmonary hypertension, erectile dysfunction, and myocardial infarction. One of its agonists, BAY 41-2272 (Riociguat), has been recently approved for treatment of pulmonary arterial hypertension (PHA), while some others are in clinical phases of development. However, the location of the binding sites for the two known types of agonists, heme-dependent stimulators and heme-independent activators, is a matter of debate, particularly for the first group where both a location on the regulatory (H-NOX) and on the catalytic domain have been suggested by different authors. Here, we address its potential location on the catalytic domain, the unique well characterized at the structural level, by an in silico approach. Homology models of the catalytic domain of sGC in inactive or active conformations were constructed using the structure of previously described crystals of the catalytic domains of inactive sGCs (2WZ1, 3ET6) and of active adenylate cyclase (1CJU). Each model was submitted to six independent molecular dynamics simulations of about 1 s. Docking of YC-1, a classic heme-dependent stimulator, to all frames of representative trajectories of inactive and active conformations, followed by calculation of absolute binding free energies with the linear interaction energy (LIE) method, revealed a potential high-affinity binding site on the active structure. The site, located between the pseudo-symmetric and the catalytic site just over the loop (2)-(3), does not overlap with the forskolin binding site on adenylate cyclases.

  • 10.
    Ahmed, Engy
    et al.
    Stockholm Univ, Dept Geol Sci, SE-10691 Stockholm, Sweden.;Stockholm Univ, Bolin Ctr Climate Res, SE-10691 Stockholm, Sweden.;Sci Life Lab, Tomtebodavagen 23A, SE-17165 Solna, Sweden..
    Parducci, Laura
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Växtekologi och evolution.
    Unneberg, Per
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär evolution.
    Ågren, Rasmus
    Chalmers Univ Technol, Dept Chem & Biol Engn, Sci Life Lab, SE-41296 Gothenburg, Sweden..
    Schenk, Frederik
    Stockholm Univ, Dept Geol Sci, SE-10691 Stockholm, Sweden.;Stockholm Univ, Bolin Ctr Climate Res, SE-10691 Stockholm, Sweden..
    Rattray, Jayne E.
    Stockholm Univ, Dept Geol Sci, SE-10691 Stockholm, Sweden.;Stockholm Univ, Bolin Ctr Climate Res, SE-10691 Stockholm, Sweden.;Univ Calgary, Biol Sci, 2500 Univ Dr NW, Calgary, AB, Canada..
    Han, Lu
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik. Jilin Univ, Coll Life Sci, Ancient DNA Lab, Changchun, Jilin, Peoples R China..
    Muschitiello, Francesco
    Stockholm Univ, Dept Geol Sci, SE-10691 Stockholm, Sweden.;Stockholm Univ, Bolin Ctr Climate Res, SE-10691 Stockholm, Sweden.;Columbia Univ, Lamont Doherty Earth Observ, 61 Route 9NW, Palisades, NY USA..
    Pedersen, Mikkel W.
    Univ Cambridge, Dept Zool, Downing St, Cambridge CB2 3EJ, England..
    Smittenberg, Rienk H.
    Stockholm Univ, Dept Geol Sci, SE-10691 Stockholm, Sweden.;Stockholm Univ, Bolin Ctr Climate Res, SE-10691 Stockholm, Sweden..
    Yamoah, Kweku Afrifa
    Stockholm Univ, Dept Geol Sci, SE-10691 Stockholm, Sweden.;Stockholm Univ, Bolin Ctr Climate Res, SE-10691 Stockholm, Sweden..
    Slotte, Tanja
    Stockholm Univ, Dept Ecol Environm & Plant Sci, SE-10691 Stockholm, Sweden.;Sci Life Lab, Tomtebodavagen 23A, SE-17165 Solna, Sweden..
    Wohlfarth, Barbara
    Stockholm Univ, Dept Geol Sci, SE-10691 Stockholm, Sweden.;Stockholm Univ, Bolin Ctr Climate Res, SE-10691 Stockholm, Sweden..
    Archaeal community changes in Lateglacial lake sediments: Evidence from ancient DNA2018Inngår i: Quaternary Science Reviews, ISSN 0277-3791, E-ISSN 1873-457X, Vol. 181, s. 19-29Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The Lateglacial/early Holocene sediments from the ancient lake at Hasseldala Port, southern Sweden provide an important archive for the environmental and climatic shifts at the end of the last ice age and the transition into the present Interglacial. The existing multi-proxy data set highlights the complex interplay of physical and ecological changes in response to climatic shifts and lake status changes. Yet, it remains unclear how microorganisms, such as Archaea, which do not leave microscopic features in the sedimentary record, were affected by these climatic shifts. Here we present the metagenomic data set of Hasseldala Port with a special focus on the abundance and biodiversity of Archaea. This allows reconstructing for the first time the temporal succession of major Archaea groups between 13.9 and 10.8 ka BP by using ancient environmental DNA metagenomics and fossil archaeal cell membrane lipids. We then evaluate to which extent these findings reflect physical changes of the lake system, due to changes in lake-water summer temperature and seasonal lake-ice cover. We show that variations in archaeal composition and diversity were related to a variety of factors (e.g., changes in lake water temperature, duration of lake ice cover, rapid sediment infilling), which influenced bottom water conditions and the sediment-water interface. Methanogenic Archaea dominated during the Allerod and Younger Dryas pollen zones, when the ancient lake was likely stratified and anoxic for large parts of the year. The increase in archaeal diversity at the Younger Dryas/Holocene transition is explained by sediment infilling and formation of a mire/peatbog. (C) 2017 Elsevier Ltd. All rights reserved.

  • 11.
    Aken, Bronwen L.
    et al.
    European Bioinformat Inst Wellcome Genome Campus, European Mol Biol Lab, Cambridge CB10 1SD, England.;Wellcome Trust Sanger Inst Wellcome Genome Campus, Cambridge CB10 1SA, England..
    Ayling, Sarah
    Wellcome Trust Sanger Inst Wellcome Genome Campus, Cambridge CB10 1SA, England.;Genome Anal Ctr, Norwich Res Pk, Norwich NR4 7UH, Norfolk, England..
    Barrell, Daniel
    European Bioinformat Inst Wellcome Genome Campus, European Mol Biol Lab, Cambridge CB10 1SD, England.;Wellcome Trust Sanger Inst Wellcome Genome Campus, Cambridge CB10 1SA, England.;Eagle Genom Ltd, Babraham Res Campus, Cambridge CB22 3AT, England..
    Clarke, Laura
    Wellcome Trust Sanger Inst Wellcome Genome Campus, Cambridge CB10 1SA, England.;European Bioinformat Inst, European Mol Biol Lab, Wellcome Genome Campus, Cambridge CB10 1SD, England..
    Curwen, Valery
    Wellcome Trust Sanger Inst Wellcome Genome Campus, Cambridge CB10 1SA, England..
    Fairley, Susan
    Wellcome Trust Sanger Inst Wellcome Genome Campus, Cambridge CB10 1SA, England.;European Bioinformat Inst, European Mol Biol Lab, Wellcome Genome Campus, Cambridge CB10 1SD, England..
    Banet, Julio Fernandez
    Wellcome Trust Sanger Inst Wellcome Genome Campus, Cambridge CB10 1SA, England.;Pfizer Inc, 10646 Sci Ctr Dr, San Diego, CA 92121 USA..
    Billis, Konstantinos
    European Bioinformat Inst Wellcome Genome Campus, European Mol Biol Lab, Cambridge CB10 1SD, England.;Wellcome Trust Sanger Inst Wellcome Genome Campus, Cambridge CB10 1SA, England..
    Giron, Carlos Garcia
    European Bioinformat Inst Wellcome Genome Campus, European Mol Biol Lab, Cambridge CB10 1SD, England.;Wellcome Trust Sanger Inst Wellcome Genome Campus, Cambridge CB10 1SA, England..
    Hourlier, Thibaut
    European Bioinformat Inst Wellcome Genome Campus, European Mol Biol Lab, Cambridge CB10 1SD, England.;Wellcome Trust Sanger Inst Wellcome Genome Campus, Cambridge CB10 1SA, England..
    Howe, Kevin
    Wellcome Trust Sanger Inst Wellcome Genome Campus, Cambridge CB10 1SA, England.;European Bioinformat Inst, European Mol Biol Lab, Wellcome Genome Campus, Cambridge CB10 1SD, England..
    Kähäri, Andreas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Beräkningsbiologi och bioinformatik. Wellcome Trust Sanger Inst Wellcome Genome Campus, Cambridge CB10 1SA, England.
    Kokocinski, Felix
    Wellcome Trust Sanger Inst Wellcome Genome Campus, Cambridge CB10 1SA, England..
    Martin, Fergal J.
    European Bioinformat Inst Wellcome Genome Campus, European Mol Biol Lab, Cambridge CB10 1SD, England.;Wellcome Trust Sanger Inst Wellcome Genome Campus, Cambridge CB10 1SA, England..
    Murphy, Daniel N.
    European Bioinformat Inst Wellcome Genome Campus, European Mol Biol Lab, Cambridge CB10 1SD, England.;Wellcome Trust Sanger Inst Wellcome Genome Campus, Cambridge CB10 1SA, England..
    Nag, Rishi
    European Bioinformat Inst Wellcome Genome Campus, European Mol Biol Lab, Cambridge CB10 1SD, England.;Wellcome Trust Sanger Inst Wellcome Genome Campus, Cambridge CB10 1SA, England..
    Ruffier, Magali
    Wellcome Trust Sanger Inst Wellcome Genome Campus, Cambridge CB10 1SA, England.;European Bioinformat Inst, European Mol Biol Lab, Wellcome Genome Campus, Cambridge CB10 1SD, England..
    Schuster, Michael
    European Bioinformat Inst Wellcome Genome Campus, European Mol Biol Lab, Cambridge CB10 1SD, England.;Austrian Acad Sci, CeMM Res Ctr Mol Med, A-1090 Vienna, Austria..
    Tang, Y. Amy
    Wellcome Trust Sanger Inst Wellcome Genome Campus, Cambridge CB10 1SA, England.;European Bioinformat Inst, European Mol Biol Lab, Wellcome Genome Campus, Cambridge CB10 1SD, England..
    Vogel, Jan-Hinnerk
    Wellcome Trust Sanger Inst Wellcome Genome Campus, Cambridge CB10 1SA, England.;Genentech Inc, 1 DNAWay, San Francisco, CA 94080 USA..
    White, Simon
    Wellcome Trust Sanger Inst Wellcome Genome Campus, Cambridge CB10 1SA, England.;Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA..
    Zadissa, Amonida
    Wellcome Trust Sanger Inst Wellcome Genome Campus, Cambridge CB10 1SA, England.;European Bioinformat Inst, European Mol Biol Lab, Wellcome Genome Campus, Cambridge CB10 1SD, England..
    Flicek, Paul
    European Bioinformat Inst Wellcome Genome Campus, European Mol Biol Lab, Cambridge CB10 1SD, England.;Wellcome Trust Sanger Inst Wellcome Genome Campus, Cambridge CB10 1SA, England..
    Searle, Stephen M. J.
    Wellcome Trust Sanger Inst Wellcome Genome Campus, Cambridge CB10 1SA, England..
    The Ensembl gene annotation system2016Inngår i: Database: The Journal of Biological Databases and Curation, ISSN 1758-0463, E-ISSN 1758-0463, artikkel-id baw093Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The Ensembl gene annotation system has been used to annotate over 70 different vertebrate species across a wide range of genome projects. Furthermore, it generates the automatic alignment-based annotation for the human and mouse GENCODE gene sets. The system is based on the alignment of biological sequences, including cDNAs, proteins and RNA-seq reads, to the target genome in order to construct candidate transcript models. Careful assessment and filtering of these candidate transcripts ultimately leads to the final gene set, which is made available on the Ensembl website. Here, we describe the annotation process in detail.

  • 12.
    Akula, Srinivas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för biologisk grundutbildning.
    Analysis of the isotype specificity of three platypus immunoglobulin Fc receptors2012Independent thesis Advanced level (degree of Master (Two Years)), 30 poäng / 45 hpOppgave
    Abstract [en]

    The host’s defense against diseases called immunity acts either via innate or adaptive defense mechanisms. Immunoglobulins (Ig’s) are important players in adaptive immunity. They have evolved both structurally and functionally during vertebrate evolution. The Fc region of Igs can interact with specific receptors on the surface of various immune cells; crosslinking of these Fc receptors can trigger a wide array of immune reactions. To trigger such reactions, higher mammals have five different classes of Igs (IgM, IgG, IgA, IgE and IgD) while amphibians, reptiles and birds have four (IgM, IgD, IgA and IgY).  Our recent studies have revealed that the early mammals (Platypus) have eight Ig isotypes (IgM, IgD IgO, IgG1, IgG2, IgA1, IgA2 and IgE) and at least four Fc receptors: FcRA, FcRB, FcRC and FcRD. In this study we investigated the specificity of three of these platypus Fc receptors to get a better picture of their isotype specificity.   

  • 13.
    Akula, Srinivas
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Mikrobiologi. Uppsala University.
    The mast cell transcriptome and the evolution of granule proteins and Fc receptors2019Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Protection against disease-causing pathogens, known as immunity, involves numerous cells organs, tissues and their products. To able to understand the biology of immune cells (hematopoietic cells) and their role in an immune system, we have used several different methods, including transcriptome analyses, bioinformatics, production of recombinant proteins and analyses of some of them, focusing on the granule proteases by substrate phage display.

    Hematopoietic cells express surface receptors interacting with the constant region of immunoglobulins (Igs) known as Fc receptors (FcRs). These receptors play major roles in the immune system, including enhancing phagocytosis, activating antibody dependent cellular cytotoxicity and cell activation. A detailed bioinformatics analysis of FcRs reveals that the poly-Ig receptors (PIGR), FcR-like molecules and common signalling γ chain all appeared very early with the appearance of the bony fishes, and thereby represent the first major evolutionary step in FcR evolution. The FcμR, FcαμR, FcγR and FcεR receptors most likely appeared in reptiles or early mammals, representing the second major step in FcR evolution.

    Cells of several of the hematopoietic cell lineages contain large numbers of cytoplasmic granules, and serine proteases constitute the major protein content of these granules. In mammals, these proteases are encoded from four different loci: the chymase, the met-ase, the granzyme (A/K) and the mast cell tryptase loci. The granzyme (A/K) locus was the first to appear and came with the cartilaginous fishes. This locus is also the most conserved of the three. The second most conserved locus is the met-ase locus, which is found in bony fishes. The chymase locus appeared relatively late, and we find the first traces in frogs, indicating it appeared in early tetrapods.

    To study the early events in the diversification of these hematopoietic serine proteases we have analyzed key characteristics of a protease expressed by an NK-like cell in the channel catfish, catfish granzyme–like I. We have used phage display and further validated the results using a panel of recombinant substrates. This protease showed a strict preference for Met at the P1 (cleavage) position, which indicates met-ase specificity. From the screening of potential in vivo substrates, we found an interesting potential target caspase 6, which indicates that caspase-dependent apoptosis mechanisms have been conserved from fishes to mammals.

    A larger quantitative transcriptome analysis of purified mouse peritoneal mast cells, cultured mast cells (BMMCs), and mast cells isolated from mouse ear and lung tissue identified the major tissue specific transcripts in these mast cells as the granule proteases. Mast cell specific receptors and processing enzymes were expressed at approximately 2 orders of magnitude lower levels. The levels of a few proteases were quite different at various anatomical sites between in vivo and cultured BMMCs. These studies have given us a new insights into mast cells in different tissues, as well as key evolutionary aspects concerning the origins of a number of granule proteases and FcRs.

    Delarbeid
    1. Fc Receptors for Immunoglobulins and Their Appearance during Vertebrate Evolution
    Åpne denne publikasjonen i ny fane eller vindu >>Fc Receptors for Immunoglobulins and Their Appearance during Vertebrate Evolution
    2014 (engelsk)Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, nr 5, s. e96903-Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Receptors interacting with the constant domain of immunoglobulins (Igs) have a number of important functions in vertebrates. They facilitate phagocytosis by opsonization, are key components in antibody-dependent cellular cytotoxicity as well as activating cells to release granules. In mammals, four major types of classical Fc receptors (FcRs) for IgG have been identified, one high-affinity receptor for IgE, one for both IgM and IgA, one for IgM and one for IgA. All of these receptors are related in structure and all of them, except the IgA receptor, are found in primates on chromosome 1, indicating that they originate from a common ancestor by successive gene duplications. The number of Ig isotypes has increased gradually during vertebrate evolution and this increase has likely been accompanied by a similar increase in isotype-specific receptors. To test this hypothesis we have performed a detailed bioinformatics analysis of a panel of vertebrate genomes. The first components to appear are the poly-Ig receptors (PIGRs), receptors similar to the classic FcRs in mammals, so called FcRL receptors, and the FcR gamma chain. These molecules are not found in cartilagous fish and may first appear within bony fishes, indicating a major step in Fc receptor evolution at the appearance of bony fish. In contrast, the receptor for IgA is only found in placental mammals, indicating a relatively late appearance. The IgM and IgA/M receptors are first observed in the monotremes, exemplified by the platypus, indicating an appearance during early mammalian evolution. Clearly identifiable classical receptors for IgG and IgE are found only in marsupials and placental mammals, but closely related receptors are found in the platypus, indicating a second major step in Fc receptor evolution during early mammalian evolution, involving the appearance of classical IgG and IgE receptors from FcRL molecules and IgM and IgA/M receptors from PIGR.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-228481 (URN)10.1371/journal.pone.0096903 (DOI)000336838000078 ()
    Tilgjengelig fra: 2014-07-15 Laget: 2014-07-15 Sist oppdatert: 2019-04-12bibliografisk kontrollert
    2. Granule Associated Serine Proteases of Hematopoietic Cells - An Analysis of Their Appearance and Diversification during Vertebrate Evolution
    Åpne denne publikasjonen i ny fane eller vindu >>Granule Associated Serine Proteases of Hematopoietic Cells - An Analysis of Their Appearance and Diversification during Vertebrate Evolution
    2015 (engelsk)Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, nr 11, artikkel-id e0143091Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Serine proteases are among the most abundant granule constituents of several hematopoietic cell lineages including mast cells, neutrophils, cytotoxic T cells and NK cells. These proteases are stored in their active form in the cytoplasmic granules and in mammals are encoded from four different chromosomal loci: the chymase locus, the met-ase locus, the T cell tryptase and the mast cell tryptase locus. In order to study their appearance during vertebrate evolution we have performed a bioinformatic analysis of related genes and gene loci from a large panel of metazoan animals from sea urchins to placental mammals for three of these loci: the chymase, met-ase and granzyme A/K loci. Genes related to mammalian granzymes A and K were the most well conserved and could be traced as far back to cartilaginous fish. Here, the granzyme A and K genes were found in essentially the same chromosomal location from sharks to humans. However in sharks, no genes clearly identifiable as members of the chymase or met-ase loci were found. A selection of these genes seemed to appear with bony fish, but sometimes in other loci. Genes related to mammalian met-ase locus genes were found in bony fish. Here, the most well conserved member was complement factor D. However, genes distantly related to the neutrophil proteases were also identified in this locus in several bony fish species, indicating that this locus is also old and appeared at the base of bony fish. In fish, a few of the chymase locus-related genes were found in a locus with bordering genes other than the mammalian chymase locus and some were found in the fish met-ase locus. This indicates that a convergent evolution rather than divergent evolution has resulted in chymase locus-related genes in bony fish.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-271027 (URN)10.1371/journal.pone.0143091 (DOI)000365070700134 ()26569620 (PubMedID)
    Forskningsfinansiär
    Swedish Research Council, 621-2011-5007
    Tilgjengelig fra: 2016-01-05 Laget: 2016-01-05 Sist oppdatert: 2019-04-12bibliografisk kontrollert
    3. Channel catfish granzyme-like I is a highly specific serine protease with metase activity that is expressed by fish NK-like cells
    Åpne denne publikasjonen i ny fane eller vindu >>Channel catfish granzyme-like I is a highly specific serine protease with metase activity that is expressed by fish NK-like cells
    2016 (engelsk)Inngår i: Developmental And Comparative Immunology, ISSN 0145-305X, Vol. 63, s. 84-95Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Here we present the extended cleavage specificity of catfish granzyme-like I, previously identified in fish NK-like cells. This protease has been characterised using substrate phage display and further validated by using a panel of recombinant substrates. A strict preference for Met in the P1 (cleavage) position, indicating metase specificity was observed. A screening of potential in vivo substrates was performed based on the derived P5-P3' consensus: Arg-Val-Thr-Gly-Met(down arrow)Ser-Leu-Val. Channel catfish caspase 6 was one very interesting potential target identified. This site was present in an adjacent position to the classic caspase activation site (Asp179 in human caspase 6). Cleavage of this site (hence potential activation) by the catfish granzyme-like I could reveal a novel mechanism of caspase 6 activation. This poses an interesting idea that the role of granzyme-like proteases in the activation of caspase dependent apoptosis mechanisms has been conserved for over 400 million years.

    Emneord
    Fish; Serine protease; Cleavage specificity; Metase; NK cell; Caspase; Evolution
    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-221554 (URN)10.1016/j.dci.2016.05.013 (DOI)000380623300010 ()27216028 (PubMedID)
    Forskningsfinansiär
    Swedish Research Council, 621-2011-5007
    Tilgjengelig fra: 2014-04-09 Laget: 2014-04-01 Sist oppdatert: 2019-04-12bibliografisk kontrollert
    4. The mouse mast cell transcriptome
    Åpne denne publikasjonen i ny fane eller vindu >>The mouse mast cell transcriptome
    Vise andre…
    (engelsk)Manuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Mast cells (MCs) are highly specialized tissue resident cells that are often found at the interphase between body and environment such as the skin, lung and intestinal mucosa. To obtain a more detailed picture of the biology of MCs we have analyzed the transcriptome of MCs from different mouse organs by RNA-seq and PCR based transcriptomics.  The results show that MCs at different tissue locations can differ quite substantially in transcript levels of several of the most abundant granule proteins even if they belong to the same basic MC type, i.e connective tissue or mucosal MCs. We can also see that transcript levels for the major granule proteins, like the various proteases and the heparin core protein can be several orders of magnitude higher than the surface receptors.  This also applies for the processing enzymes involved in activation of the proteases and in the synthesis of heparin and histamine. Interestingly also is the almost complete absence of transcripts for cytokines in the MC populations of the various organs, indicating that cytokines only are produced by activated MCs. Bone marrow derived MCs are often used as equivalents of tissue MCs.  We here show that these cells differ substantially in their transcriptome from tissue MCs. They show a transcriptome of relatively immature cells both with respect to the granule components and to the processing enzymes indicating that care should be taken when transferring findings from these cells to the in vivo function of tissue resident MCs.  This latter finding also give clear indication for that additional cytokines are needed, in addition to the stem cell factor (SCF), for the development into fully mature tissue MCs.

    HSV kategori
    Forskningsprogram
    Immunologi
    Identifikatorer
    urn:nbn:se:uu:diva-381501 (URN)
    Tilgjengelig fra: 2019-04-11 Laget: 2019-04-11 Sist oppdatert: 2019-04-15bibliografisk kontrollert
  • 14.
    Akula, Srinivas
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Mikrobiologi.
    Hellman, Lars
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Mikrobiologi.
    The Appearance and Diversification of Receptors for IgM During Vertebrate Evolution2017Inngår i: IGM AND ITS RECEPTORS AND BINDING PROTEINS / [ed] Kubagawa, H Burrows, PD, SPRINGER-VERLAG BERLIN , 2017, s. 1-23Kapittel i bok, del av antologi (Fagfellevurdert)
    Abstract [en]

    Three different receptors that interact with the constant domains of IgM have been identified: the polymeric immunoglobulin (Ig) receptor (PIGR), the dual receptor for IgA/IgM (Fc alpha mu R) and the IgM receptor (Fc mu R). All of them are related in structure and located in the same chromosomal region in mammals. The functions of the PIGRs are to transport IgM and IgA into the intestinal lumen and to saliva and tears, whereas the Fc alpha mu Rs enhance uptake of immune complexes and antibody coated bacteria and viruses by B220+ B cells and phagocytes, as well as dampening the Ig response to thymus-independent antigens. The Fc mu Rs have broad-spectrum effects on B-cell development including effects on IgM homeostasis, B-cell survival, humoral immune responses and also in autoantibody formation. The PIGR is the first of these receptors to appear during vertebrate evolution and is found in bony fish and all tetrapods but not in cartilaginous fish. The Fc mu R is present in all extant mammalian lineages and also in the Chinese and American alligators, suggesting its appearance with early reptiles. Currently the Fc alpha mu R has only been found in mammals and is most likely the evolutionary youngest of the three receptors. In bony fish, the PIGR has either 2, 3, 4, 5 or 6 extracellular Ig-like domains, whereas in amphibians, reptiles and birds it has 4 domains, and 5 in all mammals. The increase in domain number from 4 to 5 in mammals has been proposed to enhance the interaction with IgA. Both the Fc alpha mu Rs and the Fc mu Rs contain only one Ig domain; the domain that confers Ig binding. In both of these receptors this domain shows the highest degree of sequence similarity to domain 1 of the PIGR. All Ig domains of these three receptors are V type domains, indicating they all have the same origin although they have diversified extensively in function during vertebrate evolution by changing expression patterns and cytoplasmic signaling motifs.

  • 15.
    Akula, Srinivas
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi.
    Mohammadamin, Sayran
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi.
    Hellman, Lars
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Kemisk biologi.
    Fc Receptors for Immunoglobulins and Their Appearance during Vertebrate Evolution2014Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, nr 5, s. e96903-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Receptors interacting with the constant domain of immunoglobulins (Igs) have a number of important functions in vertebrates. They facilitate phagocytosis by opsonization, are key components in antibody-dependent cellular cytotoxicity as well as activating cells to release granules. In mammals, four major types of classical Fc receptors (FcRs) for IgG have been identified, one high-affinity receptor for IgE, one for both IgM and IgA, one for IgM and one for IgA. All of these receptors are related in structure and all of them, except the IgA receptor, are found in primates on chromosome 1, indicating that they originate from a common ancestor by successive gene duplications. The number of Ig isotypes has increased gradually during vertebrate evolution and this increase has likely been accompanied by a similar increase in isotype-specific receptors. To test this hypothesis we have performed a detailed bioinformatics analysis of a panel of vertebrate genomes. The first components to appear are the poly-Ig receptors (PIGRs), receptors similar to the classic FcRs in mammals, so called FcRL receptors, and the FcR gamma chain. These molecules are not found in cartilagous fish and may first appear within bony fishes, indicating a major step in Fc receptor evolution at the appearance of bony fish. In contrast, the receptor for IgA is only found in placental mammals, indicating a relatively late appearance. The IgM and IgA/M receptors are first observed in the monotremes, exemplified by the platypus, indicating an appearance during early mammalian evolution. Clearly identifiable classical receptors for IgG and IgE are found only in marsupials and placental mammals, but closely related receptors are found in the platypus, indicating a second major step in Fc receptor evolution during early mammalian evolution, involving the appearance of classical IgG and IgE receptors from FcRL molecules and IgM and IgA/M receptors from PIGR.

  • 16.
    Akula, Srinivas
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Mikrobiologi.
    Paivandy, Aida
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Thorpe, Michael
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi.
    Pjeler, Gunnar
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Hellman, Lars
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi.
    The mouse mast cell transcriptomeManuskript (preprint) (Annet vitenskapelig)
    Abstract [en]

    Mast cells (MCs) are highly specialized tissue resident cells that are often found at the interphase between body and environment such as the skin, lung and intestinal mucosa. To obtain a more detailed picture of the biology of MCs we have analyzed the transcriptome of MCs from different mouse organs by RNA-seq and PCR based transcriptomics.  The results show that MCs at different tissue locations can differ quite substantially in transcript levels of several of the most abundant granule proteins even if they belong to the same basic MC type, i.e connective tissue or mucosal MCs. We can also see that transcript levels for the major granule proteins, like the various proteases and the heparin core protein can be several orders of magnitude higher than the surface receptors.  This also applies for the processing enzymes involved in activation of the proteases and in the synthesis of heparin and histamine. Interestingly also is the almost complete absence of transcripts for cytokines in the MC populations of the various organs, indicating that cytokines only are produced by activated MCs. Bone marrow derived MCs are often used as equivalents of tissue MCs.  We here show that these cells differ substantially in their transcriptome from tissue MCs. They show a transcriptome of relatively immature cells both with respect to the granule components and to the processing enzymes indicating that care should be taken when transferring findings from these cells to the in vivo function of tissue resident MCs.  This latter finding also give clear indication for that additional cytokines are needed, in addition to the stem cell factor (SCF), for the development into fully mature tissue MCs.

  • 17.
    Akula, Srinivas
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Kemisk biologi.
    Thorpe, Michael
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Kemisk biologi.
    Boinapally, Vamsi
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Kemisk biologi.
    Hellman, Lars
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Kemisk biologi.
    Granule Associated Serine Proteases of Hematopoietic Cells - An Analysis of Their Appearance and Diversification during Vertebrate Evolution2015Inngår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, nr 11, artikkel-id e0143091Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Serine proteases are among the most abundant granule constituents of several hematopoietic cell lineages including mast cells, neutrophils, cytotoxic T cells and NK cells. These proteases are stored in their active form in the cytoplasmic granules and in mammals are encoded from four different chromosomal loci: the chymase locus, the met-ase locus, the T cell tryptase and the mast cell tryptase locus. In order to study their appearance during vertebrate evolution we have performed a bioinformatic analysis of related genes and gene loci from a large panel of metazoan animals from sea urchins to placental mammals for three of these loci: the chymase, met-ase and granzyme A/K loci. Genes related to mammalian granzymes A and K were the most well conserved and could be traced as far back to cartilaginous fish. Here, the granzyme A and K genes were found in essentially the same chromosomal location from sharks to humans. However in sharks, no genes clearly identifiable as members of the chymase or met-ase loci were found. A selection of these genes seemed to appear with bony fish, but sometimes in other loci. Genes related to mammalian met-ase locus genes were found in bony fish. Here, the most well conserved member was complement factor D. However, genes distantly related to the neutrophil proteases were also identified in this locus in several bony fish species, indicating that this locus is also old and appeared at the base of bony fish. In fish, a few of the chymase locus-related genes were found in a locus with bordering genes other than the mammalian chymase locus and some were found in the fish met-ase locus. This indicates that a convergent evolution rather than divergent evolution has resulted in chymase locus-related genes in bony fish.

  • 18.
    Akusjärvi, Göran
    et al.
    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.
    Kreivi, Jan-Peter
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk biokemi och mikrobiologi.
    Petersen-Mahrt, Svend
    Messenger RNA in Eukaryotes2007Inngår i: Encyclopedia of Life Sciences, Chichester: John Wiley , 2007, s. 1-8Kapittel i bok, del av antologi (Annet vitenskapelig)
    Abstract [en]

    Posttranscriptional regulation of gene expression represents an important level at which eukaryotes can expand the coding capacity of their genomes. The concept that one gene makes one protein does not apply to higher eukaryotes. Thus, a eukaryotic cell can use alternative ribonucleic acid (RNA) splicing, alternative polyadenylation and RNA editing to produce hundreds or even several thousands of protein isoforms from a single gene.

  • 19. Alizadehheidari, M.
    et al.
    Frykholm, K.
    Fritzsche, J.
    Wigenius, J.
    Modesti, M.
    Persson, Fredrik
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Beräknings- och systembiologi.
    Westerlund, F.
    Probing the Physical Properties of a DNA-Protein Complex Using Nanofluidic Channels2013Inngår i: European Biophysics Journal, ISSN 0175-7571, E-ISSN 1432-1017, Vol. 42, s. S134-S134Artikkel i tidsskrift (Annet vitenskapelig)
  • 20. Alizadehheidari, Mohammadreza
    et al.
    Werner, Erik
    Noble, Charleston
    Nyberg, Lena
    Fritzsche, Joachim
    Mehlig, Bernhard
    Tegenfeldt, Jonas
    Ambjoernsson, Tobias
    Persson, Fredrik
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Beräknings- och systembiologi.
    Westerlund, Fredrik
    Nanoconfined Circular DNA2014Inngår i: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 106, nr 2, s. 274A-274AArtikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    Nanofluidic channels have become a versatile tool to manipulate single DNA molecules. They allow investigation of confined single DNA molecules from a fundamental polymer physics perspective as well as for example in DNA barcoding techniques.

  • 21.
    Alizadehheidari, Mohammadreza
    et al.
    Chalmers, Biol & Biol Engn, S-41296 Gothenburg, Sweden..
    Werner, Erik
    Gothenburg Univ, Phys, Gothenburg, Sweden..
    Noble, Charleston
    Lund Univ, Phys, Lund, Sweden..
    Nyberg, Lena
    Chalmers, Biol & Biol Engn, S-41296 Gothenburg, Sweden..
    Fritzsche, Joachim
    Chalmers, Appl Phys, S-41296 Gothenburg, Sweden..
    Persson, Fredrik
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi.
    Mehlig, Bernhard
    Gothenburg Univ, Phys, Gothenburg, Sweden..
    Tegenfeldt, Jonas
    Lund Univ, Solid State Phys, Gothenburg, Sweden..
    Ambjornsson, Tobias
    Lund Univ, Phys, Lund, Sweden..
    Westerlund, Fredrik
    Chalmers, Biol & Biol Engn, S-41296 Gothenburg, Sweden..
    Unfolding of Nanoconfined Circular DNA2015Inngår i: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 108, nr 2, s. 231A-231AArtikkel i tidsskrift (Annet vitenskapelig)
  • 22. Alizadehheidari, Mohammadreza
    et al.
    Werner, Erik
    Noble, Charleston
    Reiter-Schad, Michaela
    Nyberg, Lena K.
    Fritzsche, Joachim
    Mehlig, Bernhard
    Tegenfeldt, Jonas O.
    Ambjornsson, Tobias
    Persson, Fredrik
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi.
    Westerlund, Fredrik
    Nanoconfined Circular and Linear DNA: Equilibrium Conformations and Unfolding Kinetics2015Inngår i: Macromolecules, ISSN 0024-9297, E-ISSN 1520-5835, Vol. 48, nr 3, s. 871-878Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Studies of circular DNA confined to nanofluidic channels are relevant both from a fundamental polymer-physics perspective and due to the importance of circular DNA molecules in vivo. We here observe the unfolding of confined DNA from the circular to linear configuration as a light-induced double-strand break occurs, characterize the dynamics, and compare the equilibrium conformational statistics of linear and circular configurations. This is important because it allows us to determine to what extent existing statistical theories describe the extension of confined circular DNA. We find that the ratio of the extensions of confined linear and circular DNA configurations increases as the buffer concentration decreases. The experimental results fall between theoretical predictions for the extended de Gennes regime at weaker confinement and the Odijk regime at stronger confinement. We show that it is possible to directly distinguish between circular and linear DNA molecules by measuring the emission intensity from the DNA. Finally, we determine the rate of unfolding and show that this rate is larger for more confined DNA, possibly reflecting the corresponding larger difference in entropy between the circular and linear configurations.

  • 23. Allen, Andrew J.
    et al.
    Hajdu, Janos
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär biofysik.
    Kaysser-Pyzalla, Anke R.
    Beyond the International Year of Crystallography2015Inngår i: Journal of applied crystallography, ISSN 0021-8898, E-ISSN 1600-5767, Vol. 48, nr P1, s. 1-2Artikkel i tidsskrift (Annet vitenskapelig)
  • 24.
    Allen, Andrew J.
    et al.
    NIST, Mat Measurement Sci Div Gaithersburg, MD USA.
    Hajdu, Janos
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär biofysik. AS CR, European Extreme Light Infrastruct, Inst Phys, Prague, Czech Republic..
    McIntyre, Garry J.
    Australian Nucl Sci & Technol Org, New Illawarra Rd, Lucas Heights, NSW, Australia.
    Journal of Applied Crystallography: the first 50 years and beyond2018Inngår i: Journal of applied crystallography, ISSN 0021-8898, E-ISSN 1600-5767, Vol. 51, nr Part: 2, s. 233-234Artikkel i tidsskrift (Annet vitenskapelig)
    Abstract [en]

    The Editors of Journal of Applied Crystallography mark the journal's 50th anniversary.

  • 25. Allen, Gregory S
    et al.
    Zavialov, Andrey
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Biologiska sektionen, Institutionen för cell- och molekylärbiologi. Molekylärbiologi.
    Gursky, Richard
    Ehrenberg, Måns
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Biologiska sektionen, Institutionen för cell- och molekylärbiologi. Molekylärbiologi.
    Frank, Joachim
    The cryo-EM structure of a translation initiation complex from Escherichia coli.2005Inngår i: Cell, ISSN 0092-8674, Vol. 121, nr 5, s. 703-12Artikkel i tidsskrift (Annet vitenskapelig)
  • 26.
    Allen, Marie
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylärbiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Divne, Anna-Maria
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylärbiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för immunologi, genetik och patologi.
    Universal tag arrays in forensic SNP analysis.2005Inngår i: Methods in Molecular Biology, ISSN 1064-3745, E-ISSN 1940-6029, Vol. 297, s. 141-154Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Microarray-based single nucleotide polymorphism (SNP) genotyping enables simultaneous and rapid detection of a large number of markers and is thus an attractive method for forensic individual acid identification. This assay relies on a one-color detection system and minisequencing in solution before hybridization to universal tag arrays. The minisequencing reaction is based on incorporation of a fluorescent dideoxynucleotide to a primer containing a tag-sequence flanking the position to be interrogated. This one-color system detects C and T polymorphisms in separate reactions on multiple polymerase chain reaction targets with the fluorophore TAMRA coupled to the respective dideoxynucleotide. After incorporation, tagged primer sequences are hybridized through their complementary sequence on the array, and positive signals are detected by a confocal laser-scanner.

  • 27.
    Alm, Henrik
    et al.
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Scholz, Birger
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Kultima, Kim
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Nilsson, Anna
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Andrén, Per E
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Savitski, Mikhail M
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi.
    Bergman, Åke
    Stigson, Michael
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    Fex-Svenningsen, Åsa
    Institute of Medical Biology, Anatomy and Neurobiology, University of Southern Denmark, Denmark.
    Dencker, Lennart
    Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Farmaceutiska fakulteten, Institutionen för farmaceutisk biovetenskap.
    In Vitro Neurotoxicity of PBDE-99: Immediate and Concentration-Dependent Effects on Protein Expression in Cerebral Cortex Cells2010Inngår i: Journal of Proteome Research, ISSN 1535-3893, E-ISSN 1535-3907, Vol. 9, nr 3, s. 1226-1235Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Polybrominated diphenyl ethers (PBDEs) are commonly used flame retardants in various consumer products. Pre- and postnatal exposure to congeners of PBDEs disrupts normal brain development in rodents. Two-dimensional difference gel electrophoresis (2D-DIGE) was used to analyze concentration-dependent differences in protein expression in cultured cortical cells isolated from rat fetuses (GD 21) after 24 h exposure to PBDE-99 (3, 10, or 30 muM). Changes on a post-translational level were studied using a 1 h exposure to 30 muM PBDE-99. The effects of 24 h exposure to 3 and 30 muM PBDE-99 on mRNA levels were measured using oligonucleotide microarrays. A total of 62, 46, and 443 proteins were differentially expressed compared to controls after 24 h of exposure to 3, 10, and 30 muM PDBE-99, respectively. Of these, 48, 43, and 238 proteins were successfully identified, respectively. We propose that the biological effects of low-concentration PBDE-99 exposure are fundamentally different than effects of high-concentration exposure. Low-dose PBDE-99 exposure induced marked effects on cytoskeletal proteins, which was not correlated to cytotoxicity or major morphological effects, suggesting that other more regulatory aspects of cytoskeletal functions may be affected. Interestingly, 0.3 and 3 muM, but not 10 or 30 muM increased the expression of phosphorylated (active) Gap43, perhaps reflecting effects on neurite extension processes.

  • 28.
    Almlöf, Martin
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Biologiska sektionen, Institutionen för cell- och molekylärbiologi.
    Computational Methods for Calculation of Ligand-Receptor Binding Affinities Involving Protein and Nucleic Acid Complexes2007Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    The ability to accurately predict binding free energies from computer simulations is an invaluable resource in understanding biochemical processes and drug action. Several methods based on microscopic molecular dynamics simulations exist, and in this thesis the validation, application, and development of the linear interaction energy (LIE) method is presented.

    For a test case of several hydrophobic ligands binding to P450cam it is found that the LIE parameters do not change when simulations are performed with three different force fields. The nonpolar contribution to binding of these ligands is best reproduced with a constant offset and a previously determined scaling of the van der Waals interactions.

    A new methodology for prediction of binding free energies of protein-protein complexes is investigated and found to give excellent agreement with experimental results. In order to reproduce the nonpolar contribution to binding, a different scaling of the van der Waals interactions is neccesary (compared to small ligand binding) and found to be, in part, due to an electrostatic preorganization effect not present when binding small ligands.

    A new treatment of the electrostatic contribution to binding is also proposed. In this new scheme, the chemical makeup of the ligand determines the scaling of the electrostatic ligand interaction energies. These scaling factors are calibrated using the electrostatic contribution to hydration free energies and proposed to be applicable to ligand binding.

    The issue of codon-anticodon recognition on the ribosome is adressed using LIE. The calculated binding free energies are in excellent agreement with experimental results, and further predict that the Leu2 anticodon stem loop is about 10 times more stable than the Ser stem loop in complex with a ribosome loaded with the Phe UUU codon. The simulations also support the previously suggested roles of A1492, A1493, and G530 in the codon-anticodon recognition process.

    Delarbeid
    1. Binding Affinity Prediction with Different Force Fields: Examination of the Linear Interaction Energy Method
    Åpne denne publikasjonen i ny fane eller vindu >>Binding Affinity Prediction with Different Force Fields: Examination of the Linear Interaction Energy Method
    2004 Inngår i: Journal of Computational Chemistry, ISSN 0192-8651, Vol. 25, nr 10, s. 1242-1254Artikkel i tidsskrift (Fagfellevurdert) Published
    Identifikatorer
    urn:nbn:se:uu:diva-95285 (URN)
    Tilgjengelig fra: 2006-12-22 Laget: 2006-12-22bibliografisk kontrollert
    2. Probing the Effect of Point Mutations at Protein-Protein Interfaces with Free Energy Calculations
    Åpne denne publikasjonen i ny fane eller vindu >>Probing the Effect of Point Mutations at Protein-Protein Interfaces with Free Energy Calculations
    2006 Inngår i: Biophysical Journal, ISSN 0006-3495, Vol. 90, nr 2, s. 433-442Artikkel i tidsskrift (Fagfellevurdert) Published
    Identifikatorer
    urn:nbn:se:uu:diva-95286 (URN)
    Tilgjengelig fra: 2006-12-22 Laget: 2006-12-22bibliografisk kontrollert
    3. Energetics of codon-anticodon recognition on the small ribosomal subunit
    Åpne denne publikasjonen i ny fane eller vindu >>Energetics of codon-anticodon recognition on the small ribosomal subunit
    2007 (engelsk)Inngår i: Biochemistry, ISSN 0006-2960, E-ISSN 1520-4995, Vol. 46, nr 1, s. 200-209Artikkel i tidsskrift (Fagfellevurdert) Published
    Abstract [en]

    Recent crystal structures of the small ribosomal subunit have made it possible to examine the detailed energetics of codon recognition on the ribosome by computational methods. The binding of cognate and near-cognate anticodon stem loops to the ribosome decoding center, with mRNA containing the Phe UUU and UUC codons, are analyzed here using explicit solvent molecular dynamics simulations together with the linear interaction energy (LIE) method. The calculated binding free energies are in excellent agreement with experimental binding constants and reproduce the relative effects of mismatches in the first and second codon position versus a mismatch at the wobble position. The simulations further predict that the Leu2 anticodon stem loop is about 10 times more stable than the Ser stem loop in complex with the Phe UUU codon. It is also found that the ribosome significantly enhances the intrinsic stability differences of codon-anticodon complexes in aqueous solution. Structural analysis of the simulations confirms the previously suggested importance of the universally conserved nucleotides A1492, A1493, and G530 in the decoding process.

    HSV kategori
    Identifikatorer
    urn:nbn:se:uu:diva-95287 (URN)10.1021/bi061713i (DOI)000243157300021 ()17198390 (PubMedID)
    Tilgjengelig fra: 2006-12-22 Laget: 2006-12-22 Sist oppdatert: 2017-12-14bibliografisk kontrollert
    4. Investigation of the Linear Response Approximation for Predicting Hydration Free Energies
    Åpne denne publikasjonen i ny fane eller vindu >>Investigation of the Linear Response Approximation for Predicting Hydration Free Energies
    Manuskript (Annet vitenskapelig)
    Identifikatorer
    urn:nbn:se:uu:diva-95288 (URN)
    Tilgjengelig fra: 2006-12-22 Laget: 2006-12-22 Sist oppdatert: 2010-01-13bibliografisk kontrollert
  • 29.
    Almlöf, Martin
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi.
    Andér, Martin
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi.
    Åqvist, Johan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi.
    Energetics of codon-anticodon recognition on the small ribosomal subunit2007Inngår i: Biochemistry, ISSN 0006-2960, E-ISSN 1520-4995, Vol. 46, nr 1, s. 200-209Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Recent crystal structures of the small ribosomal subunit have made it possible to examine the detailed energetics of codon recognition on the ribosome by computational methods. The binding of cognate and near-cognate anticodon stem loops to the ribosome decoding center, with mRNA containing the Phe UUU and UUC codons, are analyzed here using explicit solvent molecular dynamics simulations together with the linear interaction energy (LIE) method. The calculated binding free energies are in excellent agreement with experimental binding constants and reproduce the relative effects of mismatches in the first and second codon position versus a mismatch at the wobble position. The simulations further predict that the Leu2 anticodon stem loop is about 10 times more stable than the Ser stem loop in complex with the Phe UUU codon. It is also found that the ribosome significantly enhances the intrinsic stability differences of codon-anticodon complexes in aqueous solution. Structural analysis of the simulations confirms the previously suggested importance of the universally conserved nucleotides A1492, A1493, and G530 in the decoding process.

  • 30.
    Almlöf, Martin
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Strukturell molekylärbiologi.
    Aqvist, Johan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Strukturell molekylärbiologi.
    Smalås, Arne O
    Brandsdal, Björn O
    Probing the effect of point mutations at protein-protein interfaces with free energy calculations.2006Inngår i: Biophys J, ISSN 0006-3495, Vol. 90, nr 2, s. 433-42Artikkel i tidsskrift (Fagfellevurdert)
  • 31.
    Almlöf, Martin
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Biologiska sektionen, Institutionen för cell- och molekylärbiologi. Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Strukturell molekylärbiologi.
    Brandsdal, Bjørn O
    Aqvist, Johan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Strukturell molekylärbiologi.
    Binding affinity prediction with different force fields: examination of the2004Inngår i: J Comput Chem, ISSN 0192-8651, Vol. 25, nr 10, s. 1242-54Artikkel i tidsskrift (Fagfellevurdert)
  • 32.
    Almlöf, Martin
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Biologiska sektionen, Institutionen för cell- och molekylärbiologi.
    Brandsdal, Bjørn
    Åqvist, Johan
    Binding Affinity Prediction with Different Force Fields: Examination of the Linear Interaction Energy Method2004Inngår i: Journal of Computational Chemistry, ISSN 0192-8651, Vol. 25, nr 10, s. 1242-1254Artikkel i tidsskrift (Fagfellevurdert)
  • 33.
    Almlöf, Martin
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi.
    Carlsson, Jens
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi.
    Åqvist, Johan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi.
    Improving the accuracy of the linear interaction energy method for solvation free energies2007Inngår i: Journal of Chemical Theory and Computation, ISSN 1549-9618, E-ISSN 1549-9626, Vol. 3, nr 6, s. 2162-2175Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    A linear response method for estimating the free energy of solvation is presented and validated using explicit solvent molecular dynamics, thermodynamic perturbation calculations, and experimental data. The electrostatic contribution to the solvation free energy is calculated using a linear response estimate, which is obtained by comparison to the free energy calculated using thermodynamic perturbation. Systematic deviations from the value of 1/2 in the potential energy scaling factor are observed for some types of compounds, and these are taken into account by introducing specific coefficients for different chemical groups. The derived model reduces the rms error of the linear response estimate significantly from 1.6 to 0.3 kcal/mol on a training set of 221 molecules used to parametrize the model and from 3.7 to 1.3 kcal/mol on a test set of 355 molecules that were not used in the derivation of the model. The total solvation free energy is estimated by combining the derived model with an empirical size dependent term for predicting the nonpolar contribution. Using this model, the experimental hydration free energies for 192 molecules are reproduced with an rms error of 1.1 kcal/mol. The use of LIE in simplified binding free energy calculations to predict protein−ligand binding free energies is also discussed.

  • 34.
    Almlöf, Martin
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Biologiska sektionen, Institutionen för cell- och molekylärbiologi.
    Carlsson, Jens
    Åqvist, Johan
    Investigation of the Linear Response Approximation for Predicting Hydration Free EnergiesManuskript (Annet vitenskapelig)
  • 35.
    Almlöf, Martin
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi.
    Kristensen, Emma M. E.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Fysiska institutionen.
    Siegbahn, Hans
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Fysiska sektionen, Fysiska institutionen.
    Åqvist, Johan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi.
    Molecular dynamics study of heparin based coatings2008Inngår i: Biomaterials, ISSN 0142-9612, E-ISSN 1878-5905, Vol. 29, nr 33, s. 4463-4469Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Heparin based surface coatings can be used to improve the biocompatibility of metallic surfaces such as vascular stents. Here, we report molecular dynamics simulations of a macromolecular conjugate of heparin used to prepare such surfaces. The structural properties of the heparin conjugate are investigated for different degrees of hydration, to allow comparison with spectroscopic results. The simulations show that the polymer becomes more compact with an increasing degree of inter-chain interactions as the hydration increases. This is also accompanied by changes in the interaction patterns among the heparin chains, where counter ions become looser associated with the disaccharide units and their strong interactions can be partly replaced by water molecules and heparin hydroxyl groups. The structural information that can be obtained from computer simulations of this type of coatings can be very valuable for understanding and further development of functional interfaces, since very little is known experimentally regarding their detailed structural properties. (C) 2008 Elsevier Ltd. All rights reserved.

  • 36.
    Almlöf, Martin
    et al.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Teknisk-naturvetenskapliga fakulteten, Biologiska sektionen, Institutionen för cell- och molekylärbiologi.
    Åqvist, Johan
    Smalås, Arne
    Brandsdal, Bjørn
    Probing the Effect of Point Mutations at Protein-Protein Interfaces with Free Energy Calculations2006Inngår i: Biophysical Journal, ISSN 0006-3495, Vol. 90, nr 2, s. 433-442Artikkel i tidsskrift (Fagfellevurdert)
  • 37.
    Alneberg, Johannes
    et al.
    KTH Royal Inst Technol, Sch Engn Sci Chem Biotechnol & Hlth, Dept Gene Technol, Sci Life Lab, Stockholm, Sweden.
    Karlsson, Christofer M. G.
    Linnaeus Univ, Ctr Ecol & Evolut Microbial Model Syst, EEMiS, Kalmar, Sweden.
    Divne, Anna-Maria
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär evolution. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Bergin, Claudia
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär evolution. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Homa, Felix
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär evolution. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Lindh, Markus V.
    Linnaeus Univ, Ctr Ecol & Evolut Microbial Model Syst, EEMiS, Kalmar, Sweden;Lund Univ, Dept Biol, Lund, Sweden.
    Hugerth, Luisa W.
    KTH Royal Inst Technol, Sch Engn Sci Chem Biotechnol & Hlth, Dept Gene Technol, Sci Life Lab, Stockholm, Sweden;Karolinska Inst, Ctr Translat Microbiome Res, Dept Mol Tumour & Cell Biol, Sci Life Lab, Solna, Sweden.
    Ettema, Thijs J. G.
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för cell- och molekylärbiologi, Molekylär evolution. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Bertilsson, Stefan
    Uppsala universitet, Teknisk-naturvetenskapliga vetenskapsområdet, Biologiska sektionen, Institutionen för ekologi och genetik, Limnologi. Uppsala universitet, Science for Life Laboratory, SciLifeLab.
    Andersson, Anders F.
    KTH Royal Inst Technol, Sch Engn Sci Chem Biotechnol & Hlth, Dept Gene Technol, Sci Life Lab, Stockholm, Sweden.
    Pinhassi, Jarone
    Linnaeus Univ, Ctr Ecol & Evolut Microbial Model Syst, EEMiS, Kalmar, Sweden.
    Genomes from uncultivated prokaryotes: a comparison of metagenome-assembled and single-amplified genomes2018Inngår i: Microbiome, ISSN 0026-2633, E-ISSN 2049-2618, Vol. 6, artikkel-id 173Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Prokaryotes dominate the biosphere and regulate biogeochemical processes essential to all life. Yet, our knowledge about their biology is for the most part limited to the minority that has been successfully cultured. Molecular techniques now allow for obtaining genome sequences of uncultivated prokaryotic taxa, facilitating in-depth analyses that may ultimately improve our understanding of these key organisms.

    Results: We compared results from two culture-independent strategies for recovering bacterial genomes: single-amplified genomes and metagenome-assembled genomes. Single-amplified genomes were obtained from samples collected at an offshore station in the Baltic Sea Proper and compared to previously obtained metagenome-assembled genomes from a time series at the same station. Among 16 single-amplified genomes analyzed, seven were found to match metagenome-assembled genomes, affiliated with a diverse set of taxa. Notably, genome pairs between the two approaches were nearly identical (average 99.51% sequence identity; range 98.77-99.84%) across overlapping regions (30-80% of each genome). Within matching pairs, the single-amplified genomes were consistently smaller and less complete, whereas the genetic functional profiles were maintained. For the metagenome-assembled genomes, only on average 3.6% of the bases were estimated to be missing from the genomes due to wrongly binned contigs.

    Conclusions: The strong agreement between the single-amplified and metagenome-assembled genomes emphasizes that both methods generate accurate genome information from uncultivated bacteria. Importantly, this implies that the research questions and the available resources are allowed to determine the selection of genomics approach for microbiome studies.