umu.sePublications
Change search
Refine search result
1234567 151 - 200 of 982
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Disputation date (earliest first)
  • Disputation date (latest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the Create feeds function.
  • 151. Cornelis, M C
    et al.
    Byrne, E M
    Esko, T
    Nalls, M A
    Ganna, A
    Paynter, N
    Monda, K L
    Amin, N
    Fischer, K
    Renstrom, F
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Biobank Research.
    Ngwa, J S
    Huikari, V
    Cavadino, A
    Nolte, I M
    Teumer, A
    Yu, K
    Marques-Vidal, P
    Rawal, R
    Manichaikul, A
    Wojczynski, M K
    Vink, J M
    Zhao, J H
    Burlutsky, G
    Lahti, J
    Mikkilä, V
    Lemaitre, R N
    Eriksson, J
    Musani, S K
    Tanaka, T
    Geller, F
    Luan, J
    Hui, J
    Mägi, R
    Dimitriou, M
    Garcia, M E
    Ho, W-K
    Wright, M J
    Rose, L M
    Magnusson, P K E
    Pedersen, N L
    Couper, D
    Oostra, B A
    Hofman, A
    Ikram, M A
    Tiemeier, H W
    Uitterlinden, A G
    van Rooij, F J A
    Barroso, I
    Johansson, Ingegerd
    Umeå University, Faculty of Medicine, Department of Odontology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Biobank Research.
    Xue, L
    Kaakinen, M
    Milani, L
    Power, C
    Snieder, H
    Stolk, R P
    Baumeister, S E
    Biffar, R
    Gu, F
    Bastardot, F
    Kutalik, Z
    Jacobs, D R
    Forouhi, N G
    Mihailov, E
    Lind, L
    Lindgren, C
    Michaëlsson, K
    Morris, A
    Jensen, M
    Khaw, K-T
    Luben, R N
    Wang, J J
    Männistö, S
    Perälä, M-M
    Kähönen, M
    Lehtimäki, T
    Viikari, J
    Mozaffarian, D
    Mukamal, K
    Psaty, B M
    Döring, A
    Heath, A C
    Montgomery, G W
    Dahmen, N
    Carithers, T
    Tucker, K L
    Ferrucci, L
    Boyd, H A
    Melbye, M
    Treur, J L
    Mellström, D
    Hottenga, J J
    Prokopenko, I
    Tönjes, A
    Deloukas, P
    Kanoni, S
    Lorentzon, M
    Houston, D K
    Liu, Y
    Danesh, J
    Rasheed, A
    Mason, M A
    Zonderman, A B
    Franke, L
    Kristal, B S
    Karjalainen, J
    Reed, D R
    Westra, H-J
    Evans, M K
    Saleheen, D
    Harris, T B
    Dedoussis, G
    Curhan, G
    Stumvoll, M
    Beilby, J
    Pasquale, L R
    Feenstra, B
    Bandinelli, S
    Ordovas, J M
    Chan, A T
    Peters, U
    Ohlsson, C
    Gieger, C
    Martin, N G
    Waldenberger, M
    Siscovick, D S
    Raitakari, O
    Eriksson, J G
    Mitchell, P
    Hunter, D J
    Kraft, P
    Rimm, E B
    Boomsma, D I
    Borecki, I B
    Loos, R J F
    Wareham, N J
    Vollenweider, P
    Caporaso, N
    Grabe, H J
    Neuhouser, M L
    Wolffenbuttel, B H R
    Hu, F B
    Hyppönen, E
    Järvelin, M-R
    Cupples, L A
    Franks, Paul W
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. Department of Nutrition, Harvard School of Public Health, Boston, MA, USA; Lund Univ, Dept Clin Sci, Malmo, Sweden.
    Ridker, P M
    van Duijn, C M
    Heiss, G
    Metspalu, A
    North, K E
    Ingelsson, E
    Nettleton, J A
    van Dam, R M
    Chasman, D I
    Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption2015In: Molecular Psychiatry, ISSN 1359-4184, E-ISSN 1476-5578, Vol. 20, no 5, p. 647-656Article in journal (Refereed)
    Abstract [en]

    Coffee, a major dietary source of caffeine, is among the most widely consumed beverages in the world and has received considerable attention regarding health risks and benefits. We conducted a genome-wide (GW) meta-analysis of predominately regular-type coffee consumption (cups per day) among up to 91 462 coffee consumers of European ancestry with top single-nucleotide polymorphisms (SNPs) followed-up in ~30 062 and 7964 coffee consumers of European and African-American ancestry, respectively. Studies from both stages were combined in a trans-ethnic meta-analysis. Confirmed loci were examined for putative functional and biological relevance. Eight loci, including six novel loci, met GW significance (log10Bayes factor (BF)>5.64) with per-allele effect sizes of 0.03-0.14 cups per day. Six are located in or near genes potentially involved in pharmacokinetics (ABCG2, AHR, POR and CYP1A2) and pharmacodynamics (BDNF and SLC6A4) of caffeine. Two map to GCKR and MLXIPL genes related to metabolic traits but lacking known roles in coffee consumption. Enhancer and promoter histone marks populate the regions of many confirmed loci and several potential regulatory SNPs are highly correlated with the lead SNP of each. SNP alleles near GCKR, MLXIPL, BDNF and CYP1A2 that were associated with higher coffee consumption have previously been associated with smoking initiation, higher adiposity and fasting insulin and glucose but lower blood pressure and favorable lipid, inflammatory and liver enzyme profiles (P<5 × 10(-8)).Our genetic findings among European and African-American adults reinforce the role of caffeine in mediating habitual coffee consumption and may point to molecular mechanisms underlying inter-individual variability in pharmacological and health effects of coffee.

  • 152. Cornes, Michael P.
    et al.
    Church, Stephen
    van Dongen-Lases, Edmee
    Grankvist, Kjell
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
    Guimaraes, Joao T.
    Ibarz, Mercedes
    Kovalevskaya, Svetlana
    Kristensen, Gunn B. B.
    Lippi, Giuseppe
    Nybo, Mads
    Sprongl, Ludek
    Sumarac, Zorica
    Simundic, Ana-Maria
    The role of European Federation of Clinical Chemistry and Laboratory Medicine Working Group for Preanalytical Phase in standardization and harmonization of the preanalytical phase in Europe2016In: Annals of Clinical Biochemistry, ISSN 0004-5632, E-ISSN 1758-1001, Vol. 53, no 5, p. 539-547Article, review/survey (Refereed)
    Abstract [en]

    Patient safety is a leading challenge in healthcare and from the laboratory perspective it is now well established that preanalytical errors are the major contributor to the overall rate of diagnostic and therapeutic errors. To address this, the European Federation of Clinical Chemistry and Laboratory Medicine Working Group for Preanalytical Phase (EFLM WG-PRE) was established to lead in standardization and harmonization of preanalytical policies and practices at a European level. One of the key activities of the WG-PRE is the organization of the biennial EFLM-BD conference on the preanalytical phase to provide a forum for National Societies (NS) to discuss their issues. Since 2012, a year after the first Preanalytical phase conference, there has been a rapid growth in the number of NS with a working group engaged in preanalytical phase activities and there are now at least 19 countries that have one. As a result of discussions with NS at the third conference held in March 2015 five key areas were identified as requiring harmonisation. These were test ordering, sample transport and storage, patient preparation, sampling procedures and management of unsuitable specimens. The article below summarises the work that has and will be done in these areas. The goal of this initiative is to ensure the EFLM WG-PRE produces work that meets the needs of the European laboratory medicine community. Progress made in the identified areas will be updated at the next preanalytical phase conference and show that we have produced guidance that has enhanced standardisation in the preanalytical phase and improved patient safety throughout Europe.

  • 153.
    Costa, Tiago
    et al.
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Amer, Ayad
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Farag, Salah
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Wolf-Watz, Hans
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Fällman, Maria
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Fahlgren, Anna
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Edgren, Tomas
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Francis, Matthew
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Type III secretion translocon assemblies that attenuate Yersinia virulence2013In: Cellular Microbiology, ISSN 1462-5814, E-ISSN 1462-5822, Vol. 15, no 7, p. 1088-1110Article in journal (Refereed)
    Abstract [en]

    Type III secretion enables bacteria to intoxicate eukaryotic cells with anti-host effectors. A class of secreted cargo are the two hydrophobic translocators that form a translocon pore in the host cell plasma membrane through which the translocated effectors may gain cellular entry. In pathogenic Yersinia, YopB and YopD shape this translocon pore. Here, four in cis yopD mutations were constructed to disrupt a predicted α-helix motif at the C-terminus. Mutants YopD(I262P) and YopD(K267P) poorly localized Yop effectors into target eukaryotic cells and failed to resist uptake and killing by immune cells. These defects were due to deficiencies in host-membrane insertion of the YopD-YopB translocon. Mutants YopD(A263P) and YopD(A270P) had no measurable in vitro translocation defect, even though they formed smaller translocon pores in erythrocyte membranes. Despite this, all four mutants were attenuated in a mouse infection model. Hence, YopD variants have been generated that can spawn translocons capable of targeting effectors in vitro, yet were bereft of any lethal effect in vivo. Therefore, Yop translocators may possess other in vivo functions that extend beyond being a portal for effector delivery into host cells.

  • 154.
    Courtois-Moreau, Charleen, Laetitia
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre.
    Programmed Cell Death in Xylem Development2008Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Concerns about climate changes and scarcity of fossil fuels are rising. Hence wood is becoming an attractive source of renewable energy and raw material and these new dimensions have prompted increasing interest in wood formation in trees, in both the scientific community and wider public. In this thesis, the focus is on a key process in wood development: programmed cell death (PCD) in the development of xylem elements. Since secondary cell wall formation is dependent, inter alia, upon the life time of xylem elements, the qualitative features of wood will be affected by PCD in xylem, about which there is little information.

    This thesis focuses on the anatomical, morphological and transcriptional features of PCD during xylem development in both the stem of hybrid aspen, Populus tremula (L.) x tremuloides (Michx.) and the hypocotyl of the herbaceous model system Arabidopsis thaliana (L. Heynh.). In Populus, the progressive removal of organelles from the cytoplasm before the time of death (vacuolar bursts) and the slowness of the cell death process, illustrated by DNA fragmentation assays (such as TUNEL and Comet assays), have been ascertained in the xylem fibres by microscopic analyses. Furthermore, candidate genes for the regulation of fibre cell death were identified either from a Populus EST library obtained from woody tissues undergoing fibre cell death or from microarray experiments in Populus stem, and further assessed in an in silico comparative transcriptomic analysis of Arabidopsis thaliana. These candidate genes were either putative novel regulators of fibre cell death or members of previously described families of cell death-related genes, such as autophagy-related genes. The induction of the latter and the previous microscopic observations suggest the importance of autophagy in the degradation of the cytoplasmic contents specifically in the xylem fibres. Vacuolar bursts in the vessels were the only previously described triggers of PCD in the xylem, which induce the very rapid degradation of the nuclei and surrounding cytoplasmic contents, therefore unravelling a unique previously unrecorded type of PCD in the xylem fibres, principally involving autophagy. Arabidopsis is an attractive alternative model plant for exploring some aspects of wood formation, such as the characterisation of negative regulators of PCD. Therefore, the anatomy of Arabidopsis hypocotyls was also investigated and the ACAULIS5 (ACL5) gene, encoding an enzyme involved in polyamine biosynthesis, was identified as a key regulator of xylem specification, specifically in the vessel elements, though its negative effect on the cell death process.

    Taken together, PCD in xylem development seems to be a highly specific process, involving unique cell death morphology and molecular machinery. In addition, the technical challenges posed by the complexity of the woody tissues examined highlighted the need for specific methods for assessing PCD and related phenomena in wood.

  • 155.
    Crawford, Tim
    et al.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Lehotai, Nóra
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Strand, Åsa
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    The role of retrograde signals during plant stress responses2018In: Journal of Experimental Botany, ISSN 0022-0957, E-ISSN 1460-2431, Vol. 69, no 11, p. 2783-2795Article, review/survey (Refereed)
    Abstract [en]

    Chloroplast and mitochondria not only provide the energy to the plant cell but due to the sensitivity of organellar processes to perturbations caused by abiotic stress, they are also key cellular sensors of environmental fluctuations. Abiotic stresses result in reduced photosynthetic efficiency and thereby reduced energy supply for cellular processes. Thus, in order to acclimate to stress, plants must re-program gene expression and cellular metabolism to divert energy from growth and developmental processes to stress responses. To restore cellular energy homeostasis following exposure to stress, the activities of the organelles must be tightly co-ordinated with the transcriptional re-programming in the nucleus. Thus, communication between the organelles and the nucleus, so-called retrograde signalling, is essential to direct the energy use correctly during stress exposure. Stress-triggered retrograde signals are mediated by reactive oxygen species and metabolites including beta-cyclocitral, MEcPP (2-C-methyl-D-erythritol 2,4-cyclodiphosphate), PAP (3'-phosphoadenosine 5'-phosphate), and intermediates of the tetrapyrrole biosynthesis pathway. However, for the plant cell to respond optimally to environmental stress, these stress-triggered retrograde signalling pathways must be integrated with the cytosolic stress signalling network. We hypothesize that the Mediator transcriptional co-activator complex may play a key role as a regulatory hub in the nucleus, integrating the complex stress signalling networks originating in different cellular compartments.

  • 156. Crona, Mikael
    et al.
    Torrents, Eduard
    Rohr, Asmund K.
    Hofer, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Furrer, Ernst
    Tomter, Ane B.
    Andersson, K. Kristoffer
    Sahlin, Margareta
    Sjoberg, Britt-Marie
    NrdH-Redoxin Protein Mediates High Enzyme Activity in Manganese-reconstituted Ribonucleotide Reductase from Bacillus anthracis2011In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 286, no 38, p. 33053-33060Article in journal (Refereed)
    Abstract [en]

    Bacillus anthracis is a severe mammalian pathogen encoding a class Ib ribonucleotide reductase (RNR). RNR is a universal enzyme that provides the four essential deoxyribonucleotides needed for DNA replication and repair. Almost all Bacillus spp. encode both class Ib and class III RNR operons, but the B. anthracis class III operon was reported to encode a pseudogene, and conceivably class Ib RNR is necessary for spore germination and proliferation of B. anthracis upon infection. The class Ib RNR operon in B. anthracis encodes genes for the catalytic NrdE protein, the tyrosyl radical metalloprotein NrdF, and the flavodoxin protein NrdI. The tyrosyl radical in NrdF is stabilized by an adjacent Mn(2)(III) site (Mn-NrdF) formed by the action of the NrdI protein or by a Fe(2)(III) site (Fe-NrdF) formed spontaneously from Fe(2+) and O(2). In this study, we show that the properties of B. anthracis Mn-NrdF and Fe-NrdF are in general similar for interaction with NrdE and NrdI. Intriguingly, the enzyme activity of Mn-NrdF was approximately an order of magnitude higher than that of Fe-NrdF in the presence of the class Ib-specific physiological reductant NrdH, strongly suggesting that the Mn-NrdF form is important in the life cycle of B. anthracis. Whether the Fe-NrdF form only exists in vitro or whether the NrdF protein in B. anthracis is a true cambialistic enzyme that can work with either manganese or iron remains to be established.

  • 157. Crowe-McAuliffe, Caillan
    et al.
    Graf, Michael
    Huter, Paul
    Takada, Hiraku
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS).
    Abdelshahid, Maha
    Novácek, Jirí
    Murina, Victoriia
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Atkinson, Gemma C.
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Hauryliuk, Vasili
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Institute of Technology, University of Tartu, 50411 Tartu, Estonia.
    Wilson, Daniel N.
    Structural basis for antibiotic resistance mediated by the Bacillus subtilis ABCF ATPase VmlR2018In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 115, no 36, p. 8978-8983Article in journal (Refereed)
    Abstract [en]

    Many Gram-positive pathogenic bacteria employ ribosomal protection proteins (RPPs) to confer resistance to clinically important antibiotics. In Bacillus subtilis, the RPP VmlR confers resistance to lincomycin (Lnc) and the streptogramin A (SA) antibiotic virginiamycin M (VgM). VmlR is an ATP-binding cassette (ABC) protein of the F type, which, like other antibiotic resistance (ARE) ABCF proteins, is thought to bind to antibiotic-stalled ribosomes and promote dissociation of the drug from its binding site. To investigate the molecular mechanism by which VmlR confers antibiotic resistance, we have determined a cryo-electron microscopy (cryo-EM) structure of an ATPase-deficient B. subtilis VmlR-EQ(2) mutant in complex with a B. subtilis ErmDL-stalled ribosomal complex (SRC). The structure reveals that VmlR binds within the E site of the ribosome, with the antibiotic resistance domain (ARD) reaching into the peptidyltransferase center (PTC) of the ribosome and a C-terminal extension (CTE) making contact with the small subunit (SSU). To access the PTC, VmlR induces a conformational change in the P-site tRNA, shifting the acceptor arm out of the PTC and relocating the CCA end of the P-site tRNA toward the A site. Together with microbiological analyses, our study indicates that VmlR allosterically dissociates the drug from its ribosomal binding site and exhibits specificity to dislodge VgM, Lnc, and the pleuromutilin tiamulin (Tia), but not chloramphenicol (Cam), linezolid (Lnz), nor the macrolide erythromycin (Ery).

  • 158.
    Croxatto, Antony
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    VanT, a central regulator of quorum sensing signalling in Vibrio anguillarum2006Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Many bacteria produce signal molecules that serve in a cell-to-cell communication system termed quorum sensing. This signalling system allows a bacterial population to co-ordinately regulate functions according to their cell number in a defined environment. As bacterial growth progresses towards the stationary phase, signalling molecules accumulate in the growth medium and, above a certain threshold level, regulate the expression of genes involved in diverse functions. Most of the functions monitored by quorum sensing are most beneficial when they are performed as a population than by single cells, such as virulence factor production, biofilm formation, conjugation and bioluminescence.

    Vibrio anguillarum is a bacterial pathogen that causes terminal hemorrhagic septicaemia in marine fish. V. anguillarum possesses multiple quorum sensing circuits similar to the LuxI/LuxR and the V. harveyi-type systems. In this study, a characterisation of the quorum sensing-regulated transcriptional activator VanT was made. VanT belongs to the V. harveyi LuxR family of transcriptional regulators, which play a central role in quorum sensing signalling in Vibrio species. VanT was shown to regulate serine, metalloprotease, pigment, exopolysaccharide (EPS) and biofilm production. VanT repressed an EPS locus that plays a critical role in bacterial colonization of the fish integument and virulence.

    The V. harveyi-like quorum sensing systems were shown to limit rather than induce vanT expression throughout growth in V. anguillarum. In contrast to homologous proteins in other Vibrio spp., the quorum sensing phosphorelay protein VanU and the response regulator VanO had antagonistic roles in the regulation of vanT expression. Unlike other members of the luxR family, vanT was expressed at low cell density and no significant induction due to quorum sensing regulation was seen.

    Interestingly, VanT expression was induced by the alternative sigma factor RpoS as the cells entered stationary phase. RpoS was shown to regulate VanT expression post-transcriptionally by promoting vanT mRNA stability. VanT and RpoS were important for bacterial survival under stress conditions, indicating that VanT is likely an essential factor of V. anguillarum stress response.

  • 159.
    Croxatto, Antony
    et al.
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Pride, John
    Hardman, Andrea
    Williams, Paul
    Cámara, Miguel
    Milton, Debra L.
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    A distinctive dual-channel quorum-sensing system operates in Vibrio anguillarum2004In: Molecular Microbiology, ISSN 0950-382X, E-ISSN 1365-2958, Vol. 52, no 6, p. 1677-1689Article in journal (Refereed)
    Abstract [en]

    Many bacterial cells communicate using diffusible signal molecules to monitor cell population density via a process termed quorum sensing. In marine Vibrio species, the Vibrio harveyi-type LuxR protein is a key player in a quorum-sensing phosphorelay cascade, which controls the expression of virulence, symbiotic and survival genes. Previously, we characterized Vibrio anguillarum homologues of LuxR (VanT) and LuxMN (VanMN) and, in this study, we have identified homologues of LuxPQ (VanPQ) and LuxOU (VanOU). In contrast to other Vibrio species, vanT was expressed at low cell density and showed no significant induction as the cell number increased. In addition, although the loss of VanO increased vanT expression, the loss of VanU, unexpectedly, decreased it. Both VanN and VanQ were required for repression of vanT even in a vanU mutant, suggesting an alternative route for VanNQ signal transduction other than via VanU. VanT negatively regulated its own expression by binding and repressing the vanT promoter and by binding and activating the vanOU promoter. The signal relay results in a cellular response as expression of the metalloprotease, empA, was altered similar to that of vanT in all the mutants. Consequently, the V. anguillarum quorum-sensing phosphorelay systems work differently from those of V. harveyi and may be used to limit rather than induce vanT expression.

  • 160.
    Croxatto, Antony
    et al.
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Weber, Barbara
    Chen, Chang
    Milton, Debra L
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Post-transcriptional regulation of the Vibrio anguillarum quorum-sensing regulator vanT by RpoSManuscript (Other academic)
  • 161. Cruz-Ramírez, Alfredo
    et al.
    Díaz-Triviño, Sara
    Blilou, Ikram
    Grieneisen, Verônica A.
    Sozzani, Rosangela
    Zamioudis, Christos
    Miskolczi, Pál
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Department of Forest Genetics and Plant Physiology, Umeå Plant Science Center, Swedish University of Agricultural Sciences, Umeå, Sweden.
    Nieuwland, Jeroen
    Benjamins, René
    Dhonukshe, Pankaj
    Caballero-Pérez, Juan
    Horvath, Beatrix
    Long, Yuchen
    Mähönen, Ari Pekka
    Zhang, Hongtao
    Xu, Jian
    Murray, James A. H.
    Benfey, Philip N.
    Bako, Laszlo
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Department of Forest Genetics and Plant Physiology, Umeå Plant Science Center, Swedish University of Agricultural Sciences, Umeå, Sweden.
    Marée, Athanasius F. M.
    Scheres, Ben
    A Bistable Circuit Involving SCARECROW-RETINOBLASTOMA Integrates Cues to Inform Asymmetric Stem Cell Division2012In: Cell, ISSN 0092-8674, E-ISSN 1097-4172, Vol. 150, no 5, p. 1002-1015Article in journal (Refereed)
    Abstract [en]

    In plants, where cells cannot migrate, asymmetric cell divisions (ACDs) must be confined to the appropriate spatial context. We investigate tissue-generating asymmetric divisions in a stem cell daughter within the Arabidopsis root. Spatial restriction of these divisions requires physical binding of the stem cell regulator SCARECROW (SCR) by the RETINOBLASTOM-RELATED (RBR) protein. In the stem cell niche, SCR activity is counteracted by phosphorylation of RBR through a cyclinD6;1-CDK complex. This cyclin is itself under transcriptional control of SCR and its partner SHORT ROOT (SHR), creating a robust bistable circuit with either high or low SHR-SCR complex activity. Auxin biases this circuit by promoting CYCD6;1 transcription. Mathematical modeling shows that ACDs are only switched on after integration of radial and longitudinal information, determined by SHR and auxin distribution, respectively. Coupling of cell-cycle progression to protein degradation resets the circuit, resulting in a "flip flop" that constrains asymmetric cell division to the stem cell region.

  • 162.
    Dahrendorf, Julia
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Analysis of nitrogen utilization capability during proliferation and maturation of Norway spruce (Picea abies L. Karst) somatic embryogenesis2014Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Around 70 % of the standing trees in northern Europe are conifers, with Norway spruce being most important. To meet future wood demands, vegetative propagation methods are offering a flexible and effective way to multiply superior genotypes. The development of nitrogen metabolism during embryogenesis is not well understood and only few studies cover conifers. Norway spruce plants prefer ammonium over nitrate as an inorganic nitrogen source. However, the proliferation of somatic embryo cultures requires organic nitrogen, and ammonium nitrate as sole nitrogen source limits somatic embryo development. This raises the question how nitrogen utilization capability advances throughout the embryo development and plant formation in Norway spruce and suggests a developmental switch in nitrogen utilization capability before the plant is fully developed. Of special interest in this context is the development and activity of three key enzymes of nitrogen metabolism: nitrate reductase (NR), glutamine synthetase (GS) and arginase.

    The aim of this study was to investigate the importance of L-glutamine as an organic nitrogen source and its impact on these key enzymes of nitrogen metabolism in the proliferation and maturation stage of Norway spruce somatic embryogenesis. Therefore media with modified nitrogen sources have been used to study the effects of presence and withdrawal of L-glutamine. Pro-embryogenic masses (PEMs) grown with L-glutamine (Gln) or L-glutamine and nitrate (Gln + NO3) showed a strongly improved proliferation rate in comparison to PEMs grown on ammonium nitrate (NH4NO3). Interestingly, GS and NR were inactive enzymatically in PEMs. Arginase activity was observed, and was unaffected by the presence or absence of L-glutamine. For analyzing the importance of L-glutamine as an organic nitrogen source during maturation, somatic embryos have been generated on media with modified nitrogen sources that included also autoclaved casein hydrolysate, an amino-acid mixture that lacks L-glutamine after autoclaving. Somatic embryos matured furthest regarding size and cotyledon development on Gln + NO3. Maturation on NH4NO3 resulted in well-developed cotyledonary stage somatic embryos that were smaller in size than in the presence of L-glutamine. In mature somatic embryos GS and NR were active. NR activity was highest, if embryos were matured on Gln + NO3 and notably lower if matured on Gln or NH4NO3. The tendentially highest GS activity was found if embryos were generated on NH4NO3. A striking change in nitrogen metabolism was the steady increase in GS activity from not detectable at proliferation stage, through easily detectable during maturation up to high activity in SE plantlets.

  • 163. Davidson, Iain F.
    et al.
    Goetz, Daniela
    Zaczek, Maciej P.
    Molodtsov, Maxim I.
    in't Veld, Pim J. Huis
    Weissmann, Florian
    Litos, Gabriele
    Cisneros, David A.
    Umeå University, Faculty of Medicine, Molecular Infection Medicine Sweden (MIMS). Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Research Institute of Molecular Pathology (IMP), Vienna, Austria.
    Ocampo-Hafalla, Maria
    Ladurner, Rene
    Uhlmann, Frank
    Vaziri, Alipasha
    Peters, Jan-Michael
    Rapid movement and transcriptional re-localization of human cohesin on DNA2016In: EMBO Journal, ISSN 0261-4189, E-ISSN 1460-2075, Vol. 35, no 24, p. 2671-2685Article in journal (Refereed)
    Abstract [en]

    The spatial organization, correct expression, repair, and segregation of eukaryotic genomes depend on cohesin, ring-shaped protein complexes that are thought to function by entrapping DNA. It has been proposed that cohesin is recruited to specific genomic locations from distal loading sites by an unknown mechanism, which depends on transcription, and it has been speculated that cohesin movements along DNA could create three-dimensional genomic organization by loop extrusion. However, whether cohesin can translocate along DNA is unknown. Here, we used single-molecule imaging to show that cohesin can diffuse rapidly on DNA in a manner consistent with topological entrapment and can pass over some DNA-bound proteins and nucleosomes but is constrained in its movement by transcription and DNA-bound CCCTC-binding factor (CTCF). These results indicate that cohesin can be positioned in the genome by moving along DNA, that transcription can provide directionality to these movements, that CTCF functions as a boundary element for moving cohesin, and they are consistent with the hypothesis that cohesin spatially organizes the genome via loop extrusion.

  • 164. de Albuquerque Wanderley, Maria Carolina
    et al.
    Martín, Carlos
    Department of Chemistry and Chemical Engineering, University of Matanzas, Matanzas, Cuba; vTI-Institute for Wood Technology and Wood Biology, Hamburg, Germany.
    de Moraes Rocha, George Jackson
    Gouveia, Ester Ribeiro
    Increase in ethanol production from sugarcane bagasse based on combined pretreatments and fed-batch enzymatic hydrolysis2013In: Bioresource Technology, ISSN 0960-8524, E-ISSN 1873-2976, Vol. 128, p. 448-453Article in journal (Refereed)
    Abstract [en]

    Enzymatic hydrolysis of pretreated sugarcane bagasse was performed to investigate the production of ethanol. The sugarcane bagasse was pretreated in a process combining steam explosion and alkaline delignification. The lignin content decreased to 83%. Fed-batch enzymatic hydrolyses was initiated with 8% (w/v) solids loading, and 10 FPU/g cellulose. Then, 1% solids were fed at 12, 24 or 48 h intervals. After 120 h, the hydrolysates were fermented with Saccharomyces cerevisiae UFPEDA 1238, and a fourfold increase in ethanol production was reached when fed-batch hydrolysis with a 12-h addition period was used for the steam pretreated and delignified bagasse.

  • 165.
    De Bleser, Helena
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Crosstalk of ethylene and gibberellins during wood formation in hybridaspen2013Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Both gibberellins (GAs) and ethylene (ET) or its in planta precursor 1‐Aminocyclopropane-1‐carboxylic acid (ACC) stimulate cambial cell division and modify wood development when exogenously applied to wood forming tissues of trees. Furthermore both hormones are involved in tension wood (TW) formation in leaned trees. In Arabidopsis a cross‐talk of ET and GA on a molecular level has been demonstrated. We have examined here the effects of GA and ACC, alone and in combination, on wood development in hybrid aspen (Populus tremula x tremuloides) to investigate their potential of cross-talk during wood development. The response of selected transcripts involved in GA, ET and auxin signaling, biosynthesis and transport was inspected in the total stem of T89 trees after 10 hours of treatment with quantitative real‐time PCR (qPCR). Analysis of the phenotype, anatomy and chemistry of wild-type, ethylene-insensitive and GA‐deficient trees after 2 weeks of treatment emphasized that a cross‐talk between GA and ACC is plausible. Based on primary growth characteristics, GA and ACC seemed to be partially redundant. Lignin stainings suggest antagonistic interactions, while fiber to vessel ratios and the distribution of G‐layers put forward a collaborating action. Diffuse reflectance FT‐IR demonstrates that functional GA and ACC signalling are needed to induce differences in chemical composition.

     

  • 166.
    de La Torre, Amanda R.
    et al.
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences. Department of Plant Sciences, University of California–Davis, Davis, CA.
    Li, Zhen
    Van de Peer, Yves
    Ingvarsson, Pär K.
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences. Department of Plant Biology, Uppsala Biocenter, Swedish University of Agr icultural Sciences, Uppsala, Sweden.
    Contrasting Rates of Molecular Evolution and Patterns of Selection among Gymnosperms and Flowering Plants2017In: Molecular biology and evolution, ISSN 0737-4038, E-ISSN 1537-1719, Vol. 34, no 6, p. 1363-1377Article in journal (Refereed)
    Abstract [en]

    The majority of variation in rates of molecular evolution among seed plants remains both unexplored and unexplained. Although some attention has been given to flowering plants, reports of molecular evolutionary rates for their sister plant clade (gymnosperms) are scarce, and to our knowledge differences in molecular evolution among seed plant clades have never been tested in a phylogenetic framework. Angiosperms and gymnosperms differ in a number of features, of which contrasting reproductive biology, life spans, and population sizes are the most prominent. The highly conserved morphology of gymnosperms evidenced by similarity of extant species to fossil records and the high levels of macrosynteny at the genomic level have led scientists to believe that gymnosperms are slow-evolving plants, although some studies have offered contradictory results. Here, we used 31,968 nucleotide sites obtained from orthologous genes across a wide taxonomic sampling that includes representatives of most conifers, cycads, ginkgo, and many angiosperms with a sequenced genome. Our results suggest that angiosperms and gymnosperms differ considerably in their rates of molecular evolution per unit time, with gymnosperm rates being, on average, seven times lower than angiosperm species. Longer generation times and larger genome sizes are some of the factors explaining the slow rates of molecular evolution found in gymnosperms. In contrast to their slow rates of molecular evolution, gymnosperms possess higher substitution rate ratios than angiosperm taxa. Finally, our study suggests stronger and more efficient purifying and diversifying selection in gymnosperm than in angiosperm species, probably in relation to larger effective population sizes.

  • 167.
    De La Torre, Amanda R.
    et al.
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences. Univ British Columbia, Dept Forest & Conservat Sci, Ctr Forest Conservat Genet, Vancouver, BC V6T 1Z4, Canada.
    Roberts, David R.
    Aitken, Sally N.
    Genome-wide admixture and ecological niche modelling reveal the maintenance of species boundaries despite long history of interspecific gene flow2014In: Molecular Ecology, ISSN 0962-1083, E-ISSN 1365-294X, Vol. 23, no 8, p. 2046-2059Article in journal (Refereed)
    Abstract [en]

    The maintenance of species boundaries despite interspecific gene flow has been a continuous source of interest in evolutionary biology. Many hybridizing species have porous genomes with regions impermeable to introgression, conferring reproductive barriers between species. We used ecological niche modelling to study the glacial and postglacial recolonization patterns between the widely hybridizing spruce species Picea glauca and P.engelmannii in western North America. Genome-wide estimates of admixture based on a panel of 311 candidate gene single nucleotide polymorphisms (SNP) from 290 genes were used to assess levels of admixture and introgression and to identify loci putatively involved in adaptive differences or reproductive barriers between species. Our palaeoclimatic modelling suggests that these two closely related species have a long history of hybridization and introgression, dating to at least 21000years ago, yet species integrity is maintained by a combination of strong environmental selection and reduced current interspecific gene flow. Twenty loci showed evidence of divergent selection, including six loci that were both F-st outliers and associated with climatic gradients, and fourteen loci that were either outliers or showed associations with climate. These included genes responsible for carbohydrate metabolism, signal transduction and transcription factors.

  • 168.
    Decker, Daniel
    et al.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Kleczkowski, Leszek A.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Substrate specificity and inhibitor sensitivity of plant UDP-sugar producing pyrophosphorylasesManuscript (preprint) (Other academic)
  • 169.
    Decker, Daniel
    et al.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Meng, Meng
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Gornicka, Agnieszka
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Hofer, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Wilczynska, Malgorzata
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Kleczkowski, Leszek A
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Substrate kinetics and substrate effects on the quaternary structure of barley UDP-glucose pyrophosphorylase2012In: Phytochemistry, ISSN 0031-9422, E-ISSN 1873-3700, Vol. 79, p. 39-45Article in journal (Refereed)
    Abstract [en]

    UDP-Glc pyrophosphorylase (UGPase) is an essential enzyme responsible for production of UDP-Glc, which is used in hundreds of glycosylation reactions involving addition of Glc to a variety of compounds. In this study, barley UGPase was characterized with respect to effects of its substrates on activity and quaternary structure of the protein. Its K(m) values with Glc-1-P and UTP were 0.33 and 0.25 mM, respectively. Besides using Glc-1-P as a substrate, the enzyme had also considerable activity with Gal-1-P; however, the K(m) for Gal-1-P was very high (>10 mM), rendering this reaction unlikely under physiological conditions. UGPase had a relatively broad pH optimum of 6.5-8.5, regardless of the direction of reaction. The enzyme equilibrium constant was 0.4, suggesting slight preference for the Glc-1-P synthesis direction of the reaction. The quaternary structure of the enzyme, studied by Gas-phase Electrophoretic Mobility Macromolecule Analysis (GEMMA), was affected by addition of either single or both substrates in either direction of the reaction, resulting in a shift from UGPase dimers toward monomers, the active form of the enzyme. The substrate-induced changes in quaternary structure of the enzyme may have a regulatory role to assure maximal activity. Kinetics and factors affecting the oligomerization status of UGPase are discussed.

  • 170.
    Decker, Daniel
    et al.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Öberg, Christopher
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Kleczkowski, Leszek A.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Identification and characterization of inhibitors of UDP-glucose and UDP-sugar pyrophosphorylases for in vivo studies2017In: The Plant Journal, ISSN 0960-7412, E-ISSN 1365-313X, Vol. 90, no 6, p. 1093-1107Article in journal (Other academic)
    Abstract [en]

    UDP-sugars serve as ultimate precursors in hundreds of glycosylation reactions (e.g. for protein and lipid glycosylation, synthesis of sucrose, cell wall polysaccharides, etc.), underlying an important role of UDP-sugar-producing enzymes in cellular metabolism. However, genetic studies on mechanisms of UDP-sugar formation were frequently hampered by reproductive impairment of the resulting mutants, making it difficult to assess an in vivo role of a given enzyme. Here, a chemical library containing 17 500 compounds was separately screened against purified UDP-glucose pyrophosphorylase (UGPase) and UDP-sugar pyrophosphorylase (USPase), both enzymes representing the primary mechanisms of UDP-sugar formation. Several compounds have been identified which, at 50 μm, exerted at least 50% inhibition of the pyrophosphorylase activity. In all cases, both UGPase and USPase activities were inhibited, probably reflecting common structural features of active sites of these enzymes. One of these compounds (cmp #6), a salicylamide derivative, was found as effective inhibitor of Arabidopsis pollen germination and Arabidopsis cell culture growth. Hit optimization on cmp #6 yielded two analogs (cmp #6D and cmp #6D2), which acted as uncompetitive inhibitors against both UGPase and USPase, and were strong inhibitors in the pollen test, with apparent inhibition constants of less than 1 μm. Their effects on pollen germination were relieved by addition of UDP-glucose and UDP-galactose, suggesting that the inhibitors targeted UDP-sugar formation. The results suggest that cmp #6 and its analogs may represent useful tools to study in vivo roles of the pyrophosphorylases, helping to overcome the limitations of genetic approaches.

  • 171.
    Decker, Daniel
    et al.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Öberg, Christopher
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Kleczkowski, Leszek A.
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    The structure-activity relationship of the salicylimide derived inhibitors of UDP-sugar producing pyrophosphorylases2018In: Plant Signalling & Behavior, ISSN 1559-2316, E-ISSN 1559-2324, Vol. 13, no 8, article id e1507406Article in journal (Refereed)
    Abstract [en]

    UDP-sugars are key precursors for biomass production in nature (synthesis of cellulose, hemicellulose, etc.). They are produced de novo by distinct UDP-sugar producing pyrophosphorylases. Studies on the roles of these enzymes using genetic knockouts were hampered by sterility of the mutants and by functional-complementation from related enzyme(s), hindering clear interpretation of the results. In an attempt to override these difficulties, we turned to the reverse chemical genetics approaches to identify compounds which interfere with the activity of those enzymes in vivo. Hit expansion on one of such compounds, a salicylimide derivative, allowed us to identify several inhibitors with a range of activities. The present study provides a structure-activity relationship for these compounds.

  • 172. Deem, A
    et al.
    Keszthelyi, Andrea
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Blackgrove, T
    Vayl, A
    Coffey, B
    Mathur, R
    Chabes, Andrei
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Malkova, A
    Department of Biology, School of Science, IUPUI, Indianapolis, Indiana, United States of America.
    Break-induced replication is highly inaccurate2011In: PLoS biology, ISSN 1544-9173, E-ISSN 1545-7885Article in journal (Refereed)
    Abstract [en]

    DNA must be synthesized for purposes of genome duplication and DNA repair. While the former is a highly accurate process, short-patch synthesis associated with repair of DNA damage is often error-prone. Break-induced replication (BIR) is a unique cellular process that mimics normal DNA replication in its processivity, rate, and capacity to duplicate hundreds of kilobases, but is initiated at double-strand breaks (DSBs) rather than at replication origins. Here we employed a series of frameshift reporters to measure mutagenesis associated with BIR in Saccharomyces cerevisiae. We demonstrate that BIR DNA synthesis is intrinsically inaccurate over the entire path of the replication fork, as the rate of frameshift mutagenesis during BIR is up to 2,800-fold higher than during normal replication. Importantly, this high rate of mutagenesis was observed not only close to the DSB where BIR is less stable, but also far from the DSB where the BIR replication fork is fast and stabilized. We established that polymerase proofreading and mismatch repair correct BIR errors. Also, dNTP levels were elevated during BIR, and this contributed to BIR-related mutagenesis. We propose that a high level of DNA polymerase errors that is not fully compensated by error-correction mechanisms is largely responsible for mutagenesis during BIR, with Pol δ generating many of the mutagenic errors. We further postulate that activation of BIR in eukaryotic cells may significantly contribute to accumulation of mutations that fuel cancer and evolution.

  • 173. Dejonghe, Wim
    et al.
    Kuenen, Sabine
    Mylle, Evelien
    Vasileva, Mina
    Keech, Olivier
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Viotti, Corrado
    Swerts, Jef
    Fendrych, Matyas
    Ortiz-Morea, Fausto Andres
    Mishev, Kiril
    Delang, Simon
    Scholl, Stefan
    Zarza, Xavier
    Heilmann, Mareike
    Kourelis, Jiorgos
    Kasprowicz, Jaroslaw
    Nguyen, Le Son Long
    Drozdzecki, Andrzej
    Van Houtte, Isabelle
    Szatmari, Anna-Maria
    Majda, Mateusz
    Baisa, Gary
    Bednarek, Sebastian York
    Robert, Stephanie
    Audenaert, Dominique
    Testerink, Christa
    Munnik, Teun
    Van Damme, Daniel
    Heilmann, Ingo
    Schumacher, Karin
    Winne, Johan
    Friml, Jiri
    Verstreken, Patrik
    Russinova, Eugenia
    Mitochondrial uncouplers inhibit clathrin-mediated endocytosis largely through cytoplasmic acidification2016In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 7, article id 11710Article in journal (Refereed)
    Abstract [en]

    ATP production requires the establishment of an electrochemical proton gradient across the inner mitochondrial membrane. Mitochondrial uncouplers dissipate this proton gradient and disrupt numerous cellular processes, including vesicular trafficking, mainly through energy depletion. Here we show that Endosidin9 (ES9), a novel mitochondrial uncoupler, is a potent inhibitor of clathrin-mediated endocytosis (CME) in different systems and that ES9 induces inhibition of CME not because of its effect on cellular ATP, but rather due to its protonophore activity that leads to cytoplasm acidification. We show that the known tyrosine kinase inhibitor tyrphostinA23, which is routinely used to block CME, displays similar properties, thus questioning its use as a specific inhibitor of cargo recognition by the AP-2 adaptor complex via tyrosine motif-based endocytosis signals. Furthermore, we show that cytoplasm acidification dramatically affects the dynamics and recruitment of clathrin and associated adaptors, and leads to reduction of phosphatidylinositol 4,5-biphosphate from the plasma membrane.

  • 174.
    Del Peso-Santos, Teresa
    et al.
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Bernardo, Lisandro M D
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Skärfstad, Eleonore
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Holmfeldt, Linda
    Togneri, Peter
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Shingler, Victoria
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    A hyper-mutant of the unusual σ70-Pr promoter bypasses synergistic ppGpp/DksA co-stimulation2011In: Nucleic Acids Research, ISSN 0305-1048, E-ISSN 1362-4962, Vol. 39, no 14, p. 5853-5865Article in journal (Refereed)
    Abstract [en]

    The activities of promoters can be temporally and conditionally regulated by mechanisms other than classical DNA-binding repressors and activators. One example is the inherently weak σ70-dependent Pr promoter that ultimately controls catabolism of phenolic compounds. The activity of Pr is up-regulated through the joint action of ppGpp and DksA that enhance the performance of RNA polymerase at this promoter. Here, we report a mutagenesis analysis that revealed substantial differences between Pr and other ppGpp/DksA co-stimulated promoters. In vitro transcription and RNA polymerase binding assays show that it is the T at the −11 position of the extremely suboptimal −10 element of Pr that underlies both poor binding of σ70-RNAP and a slow rate of open complex formation—the process that is accelerated by ppGpp and DksA. Our findings support the idea that collaborative action of ppGpp and DksA lowers the rate-limiting transition energy required for conversion between intermediates on the road to open complex formation.

  • 175.
    del Peso-Santos, Teresa
    et al.
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Shingler, Victoria
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Inter-sigmulon communication through topological promoter coupling2016In: Nucleic Acids Research, ISSN 0305-1048, E-ISSN 1362-4962, Vol. 44, no 20, p. 9638-9649Article in journal (Refereed)
    Abstract [en]

    Divergent transcription from within bacterial intergenic regions frequently involves promoters dependent on alternative sigma-factors. This is the case for the non-overlapping sigma(70)- and sigma(54)-dependent promoters that control production of the substrate-responsive regulator and enzymes for (methyl) phenol catabolism. Here, using an array of in vivo and in vitro assays, we identify transcription-driven supercoiling arising from the sigma(54)-promoter as the mechanism underlying inter-promoter communication that results in stimulation of the activity of the sigma(70)-promoter. The non-overlapping 'back-to-back' configuration of a powerful sigma(54)-promoter and weak sigma(70)-promoter within this system offers a previously unknown means of inter-sigmulon communication that renders the sigma(70)-promoter subservient to signals that elicit sigma(54)-dependent transcription without it possessing a cognate binding site for the sigma(54)-RNA polymerase holoenzyme. This mode of control has the potential to be a prevalent, but hitherto unappreciated, mechanism by which bacteria adjust promoter activity to gain appropriate transcriptional control.

  • 176. Dellino, Gaetano I
    et al.
    Schwartz, Yuri B
    University of Geneva, Switzerlandc.
    Farkas, Gabriella
    McCabe, Donna
    Elgin, Sarah C R
    Pirrotta, Vincenzo
    Polycomb silencing blocks transcription initiation.2004In: Molecular Cell, ISSN 1097-2765, E-ISSN 1097-4164, Vol. 13, no 6, p. 887-93Article in journal (Refereed)
    Abstract [en]

    Polycomb (PcG) complexes maintain the silent state of target genes. The mechanism of silencing is not known but has been inferred to involve chromatin packaging to block the access of transcription factors. We have studied the effect of PcG silencing on the hsp26 heat shock promoter. While silencing does decrease the accessibility of some restriction enzyme sites to some extent, it does not prevent the binding of TBP, RNA polymerase, or the heat shock factor to the hsp26 promoter, as shown by chromatin immunoprecipitation. However, we find that in the repressed state, the RNA polymerase cannot initiate transcription. We conclude that, rather than altering chromatin structure to block accessibility, PcG silencing in this construct targets directly the activity of the transcriptional machinery at the promoter.

  • 177.
    Demakov, Sergei
    et al.
    Molecular and genetic organization of Drosophila melanogaster polytene chromosomes.
    Gortchakov, Andrei
    Molecular and genetic organization of Drosophila melanogaster polytene chromosomes.
    Schwartz, Yuri B
    Institute of Cytology & Genetics, Russian Academy of Sciences, Russia.
    Semeshin, Valery
    Molecular and genetic organization of Drosophila melanogaster polytene chromosomes.
    Campuzano, Sonsoles
    Molecular and genetic organization of Drosophila melanogaster polytene chromosomes.
    Modolell, Juan
    Molecular and genetic organization of Drosophila melanogaster polytene chromosomes.
    Zhimulev, Igor
    Molecular and genetic organization of Drosophila melanogaster polytene chromosomes.
    Molecular and genetic organization of Drosophila melanogaster polytene chromosomes: evidence for two types of interband regions2004In: Genetica, ISSN 0016-6707, E-ISSN 1573-6857, Vol. 122, no 3, p. 311-324Article in journal (Refereed)
    Abstract [en]

    The 3A and 60E regions of Drosophila melanogaster polytene chromosomes containing inserted copies of the P[1ArB] transposon have been subjected to an electron microscopic (EM) analysis. We show that both inserts led to formation of new bands within the interband regions 3A4/A6 and 60E8-9/E10. This allowed us to clone DNA of these interbands. Their sequences, as well as those of DNA from other four interbands described earlier, have been analyzed. We have found that, with the exception of 60E8-9/E10 interband, all other five regions under study corresponded to 5' or 3' ends of genes. We have further obtained the evidence for 60E8-9/E10 interband to harbor the 'housekeeping' RpL19 gene, which is transcribed in many tissues, including salivary glands. Based upon the genetic heterogeneity of the interbands observed a revised model of polytene chromosome organization is discussed.

  • 178.
    den Hollander, Jürgen
    et al.
    III. Medical Department, Technische Universität München, Munich, Germany.
    Rimpi, Sara
    Umeå University, Faculty of Science and Technology, Molecular Biology (Faculty of Science and Technology).
    Doherty, Joanne R
    Department of Cancer Biology, The Scripps Research Institute, Scripps Florida, Jupiter, Florida, USA.
    Rudelius, Martina
    Department of Pathology, Technische Universität München, Munich, Germany.
    Buck, Andreas
    Department of Nuclear Medicine, Technische Universität München, Munich, Germany.
    Kremer, Marcus
    Department of Pathology, Technische Universität München, Munich, Germany.
    Graf, Nikolas
    III. Medical Department, Technische Universität München, Munich, Germany.
    Scheerer, Markus
    III. Medical Department, Technische Universität München, Munich, Germany.
    Hall, Mark
    Department of Cancer Biology, The Scripps Research Institute, Scripps Florida, Jupiter, Florida, USA.
    von Bubnoff, Nikolas
    III. Medical Department, Technische Universität München, Munich, Germany.
    Duyster, Justus
    III. Medical Department, Technische Universität München, Munich, Germany.
    Peschel, Christian
    III. Medical Department, Technische Universität München, Munich, Germany.
    Cleveland, John L
    Department of Cancer Biology, The Scripps Research Institute, Scripps Florida, Jupiter, Florida, USA.
    Nilsson, Jonas A
    Umeå University, Faculty of Science and Technology, Molecular Biology (Faculty of Science and Technology).
    Keller, Ulrich
    III. Medical Department, Technische Universität München, Munich, Germany.
    Aurora kinases A and B are Myc targets essential for maintenance of the malignant stateManuscript (preprint) (Other academic)
  • 179. Desmarais, SN
    et al.
    Tropini, C
    Miguel, A
    Cava, Felipe
    MIMS / Umeå University.
    Monds, RD
    de Pedro, MA
    Huang, KC
    High-throughput, Highly Sensitive Analyses of Bacterial Morphogenesis Using Ultra Performance Liquid Chromatography.2015In: J Biol Chem., Vol. 25, no 290(52), p. 31090-31100Article in journal (Refereed)
  • 180. Dessouky, Ahmed M.
    et al.
    Taha, Taha E.
    Dessouky, Mohamed M.
    Eltholth, Ashraf A.
    Hassan, Emadeldeen
    Umeå University, Faculty of Science and Technology, Department of Computing Science. Department of Electronics and Electrical Communication Engineering, Faculty of Electronic Engineering, Menoufia University, Menouf, Egypt.
    Abd El-Samie, Fathi E.
    Visual representation of DNA sequences for exon detection using non-parametric spectral estimation techniques2019In: Nucleosides, Nucleotides & Nucleic Acids, ISSN 1525-7770, E-ISSN 1532-2335, Vol. 38, no 5, p. 321-337Article in journal (Refereed)
    Abstract [en]

    This paper presents a new approach for modeling of DNA sequences for the purpose of exon detection. The proposed model adopts the sum-of-sinusoids concept for the representation of DNA sequences. The objective of the modeling process is to represent the DNA sequence with few coefficients. The modeling process can be performed on the DNA signal as a whole or on a segment-by-segment basis. The created models can be used instead of the original sequences in a further spectral estimation process for exon detection. The accuracy of modeling is evaluated evaluated by using the Root Mean Square Error (RMSE) and the R-square metrics. In addition, non-parametric spectral estimation methods are used for estimating the spectral of both original and modeled DNA sequences. The results of exon detection based on original and modeled DNA sequences coincide to a great extent, which ensures the success of the proposed sum-of-sinusoids method for modeling of DNA sequences.

  • 181.
    Devadas, Arun
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Characterization of fungual strains for bioethanol production and sugar utilization2012Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Bioethanol production from cellulose based sources is currently in focus in several research projects and the need of the hour is a versatile fermenting organism that can utilize both 5C and 6C sugars effectively. Several naturally occurring fungi have the property of fermenting both types of sugars more efficiently than the traditionally used Saccharomyces cerevisiae which only can ferment hexose sugars. In this study, six different fungi were grown on a media with sugar concentrations similar to the spent sulphite liquor (SSL) from the paper pulp industry. Known fungi such as S. cerevisiae and T. versicolor as well as 4 unidentified wood rot species were grown in sealed bottles with media containing mixture of 6C and 5C. Comparison was made between ethanol fermentation, sugar consumption and enzyme activities (ALDH and PDC). The fermentation experiment was run for 21 days and ethanol concentrations up to 18g/L were achieved. We conclude that two of the fungi produce sufficient amount of ethanol and could be used in large-scale fermentation processes.

  • 182.
    Dimotakis, Charilaos
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Understanding of the role of CAD4, CAD5 and CAD6 gene redundancy during the lignification of Arabidopsis xylem.2015Independent thesis Advanced level (degree of Master (Two Years)), 40 credits / 60 HE creditsStudent thesis
    Abstract [en]

    Abstract

     

    Lignin is a cell wall polyphenolic polymer constituting the second most abundant bio-polymer on earth. This polymer is mostly accumulated in wood or xylem where it covers the other cell wall polysaccharides. Thus the removal of lignin allows accessing the polysaccharidic cell wall polymers which can then be converted into bio-fuels, textile or paper. Understanding lignin biosynthesis is therefore important to improve the industrial processing of the woody biomass. Lignin derives from the oxidative polymerization of different types of monomers called monolignols including 4-hydroxyphenylpropene alcohols as the most common monomers. Monolignols derive from the amino acid phenylalanine which is converted by a biosynthetic pathway known as the phenylpropanoid pathway. The last step of the multiple enzymatic process use the enzyme cinnamyl alcohol dehydrogenase (CAD) to convert 4-hydroxyphenylpropene aldehydes into 4-hydroxyphenylpropene alcohols. CAD is encoded by a small multigenic family in Arabidopsis thaliana comprising 17 genes.

    The aim of this master thesis is to understand the role of cinnamyl alcohol dehydrogenase gene redundancy during xylem lignification. CAD4, CAD5 and CAD6 have been associated in previous studies with xylem lignification and the main aim is to decipher if these genes are redundant or if they exhibit specificity in their expression (level, time and/or localization) and/or protein activity and structure. To do so, a genetic analysis of the single and double T-DNA insertional loss-of-function mutants in each of these genes were studied to compare their morphological characteristics, their biochemical structure (for both lignin quantification and composition) as well as their gene expression levels.

    Although minor changes in the lignin quantity and composition were observed for all of the single mutants, double mutants exhibited significant reductions and changes. Gene expression analysis moreover showed that the loss-of-function in any one of the three CADs caused a reduction ranging from 48% to 95% of the expression of the other CADs independently of the gene mutated. CAD4 and CAD5 both catalyzed the reduction of classical 4-hydroxyphenylpropene aldehydes into their corresponding alcohols: CAD5 catalytic activity is more specific to doubly methoxylated 4-hydroxyphenylpropene aldehydes than CAD4. In contrast, CAD6 did not affect the classical monolignols incorporation into lignin, but instead appeared to assist the function of CAD4 and CAD5. A clear synergetic effect of the double mutants suggested that a potential interaction could occur between these CAD proteins. Overall, our analysis showed that these three CAD genes were not redundant, but instead exhibited distinct function during xylem lignin biosynthesis.

  • 183.
    Dingeldein, Artur P. G.
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Lindberg, Mikael J.
    Umeå University, Faculty of Science and Technology, Department of Chemistry. Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Ådén, Jörgen
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Zhong, Xueyin
    Stoll, Raphael
    Gröbner, Gerhard
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Bax to the future – A novel, high-yielding approach for purification and expression of full-length Bax protein for structural studies2019In: Protein Expression and Purification, ISSN 1046-5928, E-ISSN 1096-0279, Vol. 158, p. 20-26Article in journal (Refereed)
    Abstract [en]

    Mitochondria-mediated apoptosis (programmed cell death) involves a sophisticated signaling and regulatory network that is regulated by the Bcl-2 protein family. Members of this family have either pro- or anti-apoptotic functions. An important pro-apoptotic member of this family is the cytosolic Bax. This protein is crucial for the onset of apoptosis by perforating the mitochondrial outer membrane (MOM). This process can be seen as point of no return, since disintegration of the MOM leads to the release of apotogenic factors such as cytochrome c into the cytosol triggering the activation of caspases and subsequent apoptotic steps. Bax is able to interact with the MOM with both its termini, making it inherently difficult to express in E. coli. In this study, we present a novel approach to express and purify full-length Bax with significantly increased yields, when compared to the commonly applied strategy. Using a double fusion approach with an N-terminal GST-tag and a C-terminal Intein-CBD-tag, we were able to render both Bax termini inactive and prevent disruptive interactions from occurring during gene expression. By deploying an Intein-CBD-tag at the C-terminus we were further able to avoid the introduction of any artificial residues, hence ensuring the native like activity of the membrane-penetrating C-terminus of Bax. Further, by engineering a His6-tag to the C-terminus of the CBD-tag we greatly improved the robustness of the purification procedure. We report yields for pure, full-length Bax protein that are increased by an order of magnitude, when compared to commonly used Bax expression protocols.

  • 184.
    Dingeldein, Artur Peter Günther
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Lindberg, Mikael
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Ådén, Jörgen
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Zhong, Xueyin
    Ruhr University of Bochum, Biomolecular NMR Spectroscopy.
    Stoll, Raphael
    Ruhr University of Bochum, Biomolecular NMR Spectroscopy.
    Gröbner, Gerhard
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Bax to the future: A novel, high-yielding approach for purification and expression of full-length Bax protein for structural studiesIn: Protein Expression and Purification, ISSN 1046-5928, E-ISSN 1096-0279Article in journal (Refereed)
    Abstract [en]

    Mitochondria-mediated apoptosis (programmed cell death) is tightly regulated by the B-cell CLL/lymphoma-2 (Bcl-2) protein family. The members of this family can be divided into pro- and anti-apoptotic functioning proteins. One of the most important members for executing apoptosis is the cytosolic apoptotic Bax protein. It is crucial in facilitating onset of apoptosis by disrupting and forming pores within the mitochondrial outer membrane (MOM). This pore formation is commonly viewed as a point of no return, since it releases apotogenic factors such as cytochrome c into the cytosol who trigger irreversibly cell death by caspase activation and nuclear fragmentation. Bax is able to interact with the MOM with both its termini, making it inherently difficult to express in E. coli due to the strong similarities between both membrane-active segments. Here, we present a novel approach to express and purify full-length Bax with significantly increased yields compared to the commonly applied strategy with very bad yields. Using a double fusion approach with an N-terminal GST-tag and a C-terminal Intein-CBD-tag, we rendered both Bax termini inactive and prevented disruptive interactions during gene expression. By deploying an Intein-CBD-tag at the C-terminus we avoided even the introduction of any artificial residues, hence ensuring the native like activity of the membrane-penetrating C-terminus of Bax. Further, by engineering a His6-tag to the C-terminus of the CBD-tag we greatly improved the purification procedure. Yields for pure, full-length Bax protein are increased by an order of magnitude, compared to commonly used Bax expression protocols.

  • 185.
    Dinh, Ngoc Phuoc
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Jonsson, Tobias
    Merck SeQuant AB, Box 7956, S-90719 Umeå, Sweden.
    Irgum, Knut
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Probing the interaction mode in hydrophilic interaction chromatography2011In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1218, no 35, p. 5880-5891Article in journal (Refereed)
    Abstract [en]

    This work aims at characterizing interactions between a select set of probes and 22 hydrophilic and polar commercial stationary phases, to develop an understanding of the relationship between the chemical properties of those phases and their interplay with the eluent and solutes in hydrophilic interaction chromatography. "Hydrophilic interaction" is a somewhat inexact term, and an attempt was therefore made to characterize the interactions involved in HILIC as hydrophilic, hydrophobic, electrostatic, hydrogen bonding, dipole-dipole, π-π interaction, and shape-selectivity. Each specific interaction was quantified from the separation factors of a pair of similar substances of which one had properties promoting the interaction mode being probed while the other did not. The effects of particle size and pore size of the phases on retention and selectivity were also studied. The phases investigated covered a wide range of surface functional groups including zwitterionic (sulfobetaine and phosphocholine), neutral (amide and hydroxyl), cationic (amine), and anionic (sulfonic acid and silanol). Principal component analysis of the data showed that partitioning was a dominating mechanism for uncharged solutes in HILIC. However, correlations between functional groups and interactions were also observed, which confirms that the HILIC retention mechanism is partly contributed by adsorption mechanisms involving electrostatic interaction and multipoint hydrogen bonding. Phases with smaller pore diameters yielded longer retention of solutes, but did not significantly change the column selectivities. The particle diameter had no significant effect, neither on retention, nor on the selectivities. An increased water content in the eluent reduced the multipoint hydrogen bonding interactions, while an increased electrolyte concentration lowered the selectivities of the tested columns and made their interaction patterns more similar.

  • 186.
    Dinh, Ngoc Phuoc
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry. Merck SeQuant AB, Umeå.
    Jonsson, Tobias
    Merck SeQuant AB, Umeå.
    Irgum, Knut
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Water uptake on polar stationary phases under conditions for hydrophilic interaction chromatography and its relation to solute retention2013In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1320, p. 33-47Article in journal (Other academic)
    Abstract [en]

    In hydrophilic interaction chromatography, water is known to accumulate on the stationary phase to form a water enriched layer, which is believed to play an important role in the retention mechanism. To gain a better understanding retention mechanism in HILIC, we have determined the water uptake on twelve different HILIC stationary phases. Non-modified and monomerically functionalized silica phases followed a pattern of monolayer formation followed by multiple layer adsorption, while the water uptake on polymerically functionalized silica stationary phase showed the characteristics of formation and swelling of hydrogels. This difference in the nature of water accumulation was found to be related to different water uptake patterns when methanol and tetrahydrofuran were added to 80:20 % (v/v) acetonitrile/water by replacing 5 % of the acetonitrile as tertiary solvents, and also when ammonium acetate was added as buffering electrolyte. The relationship between water uptake and retention mechanism was investigated by looking at the correlation between retention factors of neutral analytes and phase ratios of HILIC columns, calculated either as surface area (adsorption) or volume of the water layer enriched from the acetonitrile/water eluent (partitioning). Regardless of the adsorption or partitioning mechanism, the interaction of neutral analytes and stationary phase could be mainly the hydrogen bonding between analytes and the accumulated water in the water enriched layer.

  • 187. Dixon, Christopher J
    et al.
    Schoenswetter, Peter
    Suda, Jan
    Wiedermann, Magdalena M
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences.
    Schneeweiss, Gerald M
    Reciprocal Pleistocene origin and postglacial range formation of an allopolyploid and its sympatric ancestors (Androsace adfinis group, Primulaceae)2009In: Molecular Phylogenetics and Evolution, ISSN 1055-7903, E-ISSN 1095-9513, Vol. 50, no 1, p. 74-83Article in journal (Refereed)
    Abstract [en]

    The biogeographic history of polyploids and their lower-ploid ancestors is an important feature to achieve a better understanding of polyploid evolution. This is exemplified here using the ecologically congruent members of the Androsace adfinis group (Primulaceae) endemic to the southwestern European Alps. Employing relative genome size, AFLP fingerprint and chloroplast sequence haplotype data, we show that Androsace brigantiaca is a recent (probably no more than 0.2 million years) allopolyploid derivative of the geographically close A adfinis and A puberula, which formed reciprocally in a comparatively restricted area in the southern Southwestern Alps. Bayesian admixture analysis-also of artificial additive AFLP profiles-shows that the nuclear genome of A. brigantiaca is significantly biased towards the puberula-genome irrespective of maternal parentage. Nevertheless, there is no evidence for genetic interaction (hybridization, introgression) of A brigantiaca with either of its ancestors, including the widely sympatric A. puberula. Sympatry might be facilitated by ecological displacement on a local scale or might be a transitory phase on the way to competitive replacement via, for instance, polyploid superiority.

  • 188.
    Do, Lan
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Geladi, Paul
    Haglund, Peter
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Multivariate data analysis to characterize gas chromatography columns for dioxin analysis2014In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1347, p. 137-145Article in journal (Refereed)
    Abstract [en]

    Principal component analysis (PCA) was applied for evaluating the selectivity of 22 GC columns for which complete retention data were available for the 136 tetra- to octa-chlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs). Because the hepta- and octa-homologues are easy to separate the PCA was focused on the 128 tetra- to hexa-CDD/Fs. The analysis showed that 21 of the 22 GC columns could be subdivided into four groups with different selectivity. Group I consists of columns with non-polar thermally stable phases (Restek 5Sil MS and Dioxin 2, SGE BPX-DXN, Supelco Equity-5, and Agilent DB-1, DB-5, DB-5ms, VF-5ms, VF-Xms and DB-XLB). Group II includes ionic liquid columns (Supelco SLB-IL61, SLB-IL111 and SLB-IL76) with very high polarity. Group III includes columns with high-percentage phenyl and cyanopropyl phases (Agilent DB-17 and DB-225, Quadrex CPS-1, Supelco SP-2331, and Agilent CP-Sil 88), and Group IV columns with shape selectivity (Dionex SB-Smectic and Restek LC-50, Supelco beta DEXcst, Agilent VF-Xms and DB-XLB). Thus, two columns appeared in both Group I and IV (Agilent VF-Xms and DB-XLB). The selectivity of the other column, Agilent DB-210, differs from those of these four groups. Partial least squares (PLS) regression was used to correlate the retention times of the tetra- to hexa-CDD/Fs on the 22 stationary phases with a set of physicochemical and structural descriptors to identify parameters that significantly influence the solute-stationary phase interactions. The most influential physicochemical parameters for the interaction were associated with molecular size (as reflects in the total energy, electron energy, core-core repulsion and standard entropy), solubility (aqueous solubility and n-octanol/water partition coefficient), charge distribution (molecular polarizability and dipolar moment), and reactivity (relative Gibbs free energy); and the most influential structural descriptors were related to these parameters, in particular, size and dipolar moment. Finally, the PCA and PLS analyses were complemented with linear regression analysis to identify the most orthogonal column combinations, which could be used in comprehensive two-dimensional gas chromatography (GC x GC) to enhance PCDD/F separation and congener profiling. (C) 2014 Elsevier B.V. All rights reserved.

  • 189.
    Do, Lan
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Liljelind, Per
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Zhang, Jin
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Haglund, Peter
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Comprehensive profiling of 136 tetra- to octa-polychlorinated dibenzo-p-dioxins and dibenzofurans using ionic liquid columns and column combinations2013In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1311, p. 157-169Article in journal (Refereed)
    Abstract [en]

    The orders of elution of all 136 tetra- to octa-chlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) were determined on six gas chromatography (GC) columns. Three of these columns had ionic liquid stationary phases (SLB-IL111, SLB-IL76 and SLB-IL61; Supelco), one a liquid crystal phase (LC-50; Restek), one a chiral phase (beta DEXcst; Restek) and one a low bleed non-polar phase (DB-XLB; J&W/Agilent). According to our results, the high polarity and multiple solvation interactions of the ionic liquid stationary phases offered superior resolving power to that achieved with previously evaluated columns. The SLB-IL61 and SLB-IL111 columns resolved or partially separated 106 and 100 congeners, respectively, of the 136 PCDD/Fs. The SLB-IL61 also resolved 15 and partially separated one of the seventeen 2,3,7,8-substituted PCDD/Fs. Additional congeners can be separated by complementary analyses using additional columns in a dual- or triple-column approach. For example, using a combination of the SLB-IL61 and SLB-IL111 columns all but 8 congeners would be separated, including all 2,3,7,8-substituted PCDD/Fs. Two more congeners would be separated using a combination of SLB-IL76 and a liquid crystal (SB-Smectic) column, but in this case the 2,3,7,8-TeCDF would not be resolved. Three-column combinations would give even better separation: the DB-17/Smectic/SLB-IL76 and DB-225/Smectic/SLB-IL111 combinations would separate all but 1 of the 136 PCDD/F congeners. Unfortunately, the smectic column is no longer in production. If only commercially available columns are considered, combinations of SLB-IL61 and SLB-IL111 with DB-XLB, LC-50, or DB-225 offer the best performance, with 4, 4, and 3 unresolved congeners, respectively. Moreover, in each of these cases, one of the congeners in each unresolved pair is resolved on at least one of the other columns and so a reasonable estimate of the unresolved congeners' concentrations can be obtained by subtraction. The profiling of all 136 PCDD/Fs is thus greatly facilitated by using ionic liquid columns or combinations including such columns. However, there is room for improvement in the technical performance of the evaluated ionic liquid columns: their long-term retention time stability was poor and some highly chlorinated and sterically hindered congeners underwent dehalogenation during separation.

    (C) 2013 Elsevier B.V. All rights reserved.

  • 190.
    Dobrenel, Thomas
    et al.
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Institut Jean-Pierre Bourgin, Institut National de la Recherche Agronomique, AgroParisTech, Centre National de la Recherche Scientifique, Université Paris-Saclay, Versailles, France; Université Paris-Sud–Université Paris-Saclay, Orsay, France.
    Mancera-Martinez, Eder
    Forzani, Celine
    Azzopardi, Marianne
    Davanture, Marlene
    Moreau, Manon
    Schepetilnikov, Mikhail
    Chicher, Johana
    Langella, Olivier
    Zivy, Michel
    Robaglia, Christophe
    Ryabova, Lyubov A.
    Hanson, Johannes
    Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC). Umeå University, Faculty of Science and Technology, Department of Plant Physiology.
    Meyer, Christian
    The Arabidopsis TOR Kinase Specifically Regulates the Expression of Nuclear Genes Coding for Plastidic Ribosomal Proteins and the Phosphorylation of the Cytosolic Ribosomal Protein S62016In: Frontiers in Plant Science, ISSN 1664-462X, E-ISSN 1664-462X, Vol. 7, article id 1611Article in journal (Refereed)
    Abstract [en]

    Protein translation is an energy consuming process that has to be fine-tuned at both the cell and organism levels to match the availability of resources. The target of rapamycin kinase (TOR) is a key regulator of a large range of biological processes in response to environmental cues. In this study, we have investigated the effects of TOR inactivation on the expression and regulation of Arabidopsis ribosomal proteins at different levels of analysis, namely from transcriptomic to phosphoproteomic. TOR inactivation resulted in a coordinated down-regulation of the transcription and translation of nuclear-encoded mRNAs coding for plastidic ribosomal proteins, which could explain the chlorotic phenotype of the TOR silenced plants. We have identified in the 5' untranslated regions (UTRs) of this set of genes a conserved sequence related to the 5' terminal oligopyrimidine motif, which is known to confer translational regulation by the TOR kinase in other eukaryotes. Furthermore, the phosphoproteomic analysis of the ribosomal fraction following TOR inactivation revealed a lower phosphorylation of the conserved Ser240 residue in the C-terminal region of the 40S ribosomal protein S6 (RPS6). These results were confirmed by Western blot analysis using an antibody that specifically recognizes phosphorylated Ser240 in RPS6. Finally, this antibody was used to follow TOR activity in plants. Our results thus uncover a multi-level regulation of plant ribosomal genes and proteins by the TOR kinase.

  • 191.
    Domar, Ulla
    Umeå University, Faculty of Medicine, Department of Medical Biochemistry and Biophysics.
    Human intestinal alkaline phosphatase: tissue expression and serum levels1992Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Human alkaline phosphatase (ALP) comprises four isozymes, viz liver/bone/ kidney or tissue unspecific (AP), intestinal (LAP), placental (PLAP) and germ cell or PLAP-like alkaline phosphatase, with their main expression in specific tissues as indicated by their names. The isozymes are coded by different genes, but they are closely related, with more than 50% amino acid sequence homologies. Their biological function is unclear. In certain malignant and benign diseases, serum elevations of one or more of the isozymes occur, which is of diagnostic importance. In this study, the special expression of the intestinal isozyme in human tissues and sera, in normal as well as in pathological conditions, has been investigated by use of isozyme specific monoclonal antibodies.

    Monoclonal antibodies against the AP, IAP and PLAP isozymes were prepared, and specific assays developed, based on these monoclonal antibodies and the catalytic activity of the isozymes. By use of these assays the basal levels of all three isozymes were examined in selected normal organs. The isozymes were found to be expressed in measurable amounts in all the examined organs.

    IAP was immunohistochemically localized to the epithelial cells of membranes lining the ducts and tubules of the kidney, liver, pancreas and small intestine.

    Normal human serum contained all three isozymes. The AP isozyme constituted about 90% of the total ALP activity, the IAP isozyme less than 10% and the PLAP isozyme about 1%. Considerable interindividual variations of the serum IAP activity were observed. The serum activities of the IAP isozyme were related to the individual ABO blood group and secretor status. Non-secretors had low levels of IAP activity amounting to about one tenth of the activity in sera from blood group B or 0 secretors, while blood group A secretors had serum IAP activities in the same order as non-secretors. High individual day to day variations were observed.

    Fat absorption caused serum IAP to increase significantly for all persons, but it was rapidly cleared from the blood. We found that the release of IAP into the blood was linked to lipid absorption, but removal from the blood was not linked to lipoprotein clearance.

    Certain tumors of the testis expressed elevated levels of all three ALP isozymes. The highest activitiy of LAP was observed in one yolk sac tumor, in agreement with the endodermal origin of this tumor. In seminoma tissue the AP and PLAP isozymes were significantly, and IAP moderately elevated.

    Cirrhosis of the liver caused significantly increased serum levels of IAP besides the AP isozyme. In inflammatory diseases of the small intestine, normal serum IAP activities were observed.

  • 192. Domingo-Almenara, Xavier
    et al.
    Montenegro-Burke, J. Rafael
    Ivanisevic, Julijana
    Thomas, Aurelien
    Sidibé, Jonathan
    Teav, Tony
    Guijas, Carlos
    Aisporna, Aries E.
    Rinehart, Duane
    Hoang, Linh
    Nordström, Anders
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Gómez-Romero, Maria
    Whiley, Luke
    Lewis, Matthew R.
    Nicholson, Jeremy K.
    Benton, H. Paul
    Siuzdak, Gary
    CMS-MRM and METLIN-MRM: a cloud library and public resource for targeted analysis of small molecules2018In: Nature Methods, ISSN 1548-7091, E-ISSN 1548-7105, Vol. 15, no 9, p. 681-+Article in journal (Refereed)
    Abstract [en]

    We report XCMS-MRM and METLIN-MRM (http://xcmsonline-mrm.scripps.edu/ and http://metlin.scripps.edu/), a cloud-based data-analysis platform and a public multiple-reaction monitoring (MRM) transition repository for small-molecule quantitative tandem mass spectrometry. This platform provides MRM transitions for more than 15,500 molecules and facilitates data sharing across different instruments and laboratories.

  • 193. Dongre, Mitesh
    et al.
    Khatri, Neelam
    Dureja, Chetna
    Raychaudhuri, Saumya
    Alanine-scanning mutagenesis of selected residues in the N-terminal region alters the functionality of LuxO: lessons from a natural variant LuxOPL91.2011In: Journal of Medical Microbiology, ISSN 0022-2615, E-ISSN 1473-5644, Vol. 60, no Pt 6, p. 856-60Article in journal (Refereed)
  • 194. Dongre, Mitesh
    et al.
    Singh, Naorem Santa
    Dureja, Chetna
    Peddada, Nagesh
    Solanki, Ashish K
    Ashish, Ganguly
    Raychaudhuri, Saumya
    Evidence on how a conserved glycine in the hinge region of HapR regulates its DNA binding ability: lessons from a natural variant.2011In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 286, no 17, p. 15043-9Article in journal (Refereed)
    Abstract [en]

    HapR has been recognized as a quorum-sensing master regulator in Vibrio cholerae. Because it controls a plethora of disparate cellular events, the absence of a functional HapR affects the physiology of V. cholerae to a great extent. In the current study, we pursued an understanding of an observation of a natural protease-deficient non-O1, non-O139 variant V. cholerae strain V2. Intriguingly, a nonfunctional HapR (henceforth designated as HapR(V2)) harboring a substitution of glycine to aspartate at position 39 of the N-terminal hinge region has been identified. An in vitro gel shift assay clearly suggested the inability of HapR(V2) to interact with various cognate promoters. Reinstatement of glycine at position 39 restores DNA binding ability of HapR(V2) (HapR(V2G)), thereby rescuing the protease-negative phenotype of this strain. The elution profile of HapR(V2) and HapR(V2G) proteins in size-exclusion chromatography and their circular dichroism spectra did not reflect any significant differences to explain the functional discrepancies between the two proteins. To gain insight into the structure-function relationship of these two proteins, we acquired small/wide angle x-ray scattering data from samples of the native and G39D mutant. Although Guinier analysis and indirect Fourier transformation of scattering indicated only a slight difference in the shape parameters, structure reconstruction using dummy amino acids concluded that although HapR adopts a "Y" shape similar to its crystal structure, the G39D mutation in hinge drastically altered the DNA binding domains by bringing them in close proximity. This altered spatial orientation of the helix-turn-helix domains in this natural variant provides the first structural evidence on the functional role of the hinge region in quorum sensing-related DNA-binding regulatory proteins of Vibrio spp.

  • 195. Dongre, Mitesh
    et al.
    Tripathi, Ranjana
    Jain, Vibhu
    Raychaudhuri, Saumya
    Functional independence of a variant LuxOPL91 from a non-O1 non-O139 Vibrio cholerae over the activity of CsrA and Fis.2008In: Journal of Medical Microbiology, ISSN 0022-2615, E-ISSN 1473-5644, Vol. 57, no Pt 8, p. 1041-5Article in journal (Refereed)
  • 196.
    Dongre, Mitesh
    et al.
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    Wai, Sun Nyunt
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR).
    The Protease of Vibrio cholerae (PrtV)2013In: Handbook of proteolytic enzymes: volume 1 / [ed] Neil D. Rawlings, Guy Salvesen, Elsevier, 2013, 3, Vol. 1, p. 1219-1225Chapter in book (Refereed)
    Abstract [en]

    The third edition of the Handbook of Proteolytic Enzymes aims to be a comprehensive reference work for the enzymes that cleave proteins and peptides, and contains over 850 chapters. Each chapter is organized into sections describing the name and history, activity and specificity, structural chemistry, preparation, biological aspects, and distinguishing features for a specific peptidase. The subject of Chapter 273 is The Protease of Vibrio cholerae (PrtV). Keywords Auto-proteolysis, Caenorhabditis elegans, cytokine induction, fibrinogen, fibronectin, HapR. Vibrio cholerae cytolysin (VCC), M6-peptidase family, plasminogen, polycystic kidney disease (PKD) domains, Quorum Sensing (QS), zinc-dependent metalloproteases.

  • 197.
    Dorafshan, Eshagh
    et al.
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Kahn, Tatyana G.
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Glotov, Alexander
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Savitsky, Mikhail
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Walther, Matthias
    Reuter, Gunter
    Schwartz, Yuri B.
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Ash1 counteracts Polycomb repression independent of histone H3 lysine 36 methylation2019In: EMBO Reports, ISSN 1469-221X, E-ISSN 1469-3178, Vol. 20, no 4, article id e46762Article in journal (Refereed)
    Abstract [en]

    Polycomb repression is critical for metazoan development. Equally important but less studied is the Trithorax system, which safeguards Polycomb target genes from the repression in cells where they have to remain active. It was proposed that the Trithorax system acts via methylation of histone H3 at lysine 4 and lysine 36 (H3K36), thereby inhibiting histone methyltransferase activity of the Polycomb complexes. Here we test this hypothesis by asking whether the Trithorax group protein Ash1 requires H3K36 methylation to counteract Polycomb repression. We show that Ash1 is the only Drosophila H3K36-specific methyltransferase necessary to prevent excessive Polycomb repression of homeotic genes. Unexpectedly, our experiments reveal no correlation between the extent of H3K36 methylation and the resistance to Polycomb repression. Furthermore, we find that complete substitution of the zygotic histone H3 with a variant in which lysine 36 is replaced by arginine does not cause excessive repression of homeotic genes. Our results suggest that the model, where the Trithorax group proteins methylate histone H3 to inhibit the histone methyltransferase activity of the Polycomb complexes, needs revision.

  • 198.
    Dorafshan, Eshagh
    et al.
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Kahn, Tatyana G.
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Schwartz, Yuri B.
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Hierarchical recruitment of Polycomb complexes revisited2017In: Nucleus, ISSN 1949-1034, E-ISSN 1949-1042, Vol. 8, no 5, p. 496-505Article in journal (Refereed)
    Abstract [en]

    Polycomb Group (PcG) proteins epigenetically repress key developmental genes and thereby control alternative cell fates. PcG proteins act as complexes that can modify histones and these histone modifications play a role in transmitting the memory of the repressed state as cells divide. Here we consider mainstream models that link histone modifications to hierarchical recruitment of PcG complexes and compare them to results of a direct test of interdependence between PcG complexes for recruitment to Drosophila genes. The direct test indicates that PcG complexes do not rely on histone modifications to recognize their target genes but use them to stabilize the interactions within large chromatin domains. It also shows that multiple strategies are used to coordinate the targeting of PcG complexes to different genes, which may make the repression of these genes more or less robust.

  • 199. Drotz, Marcus K.
    et al.
    Savolainen, Eino
    Saura, Anssi
    Umeå University, Faculty of Science and Technology, Department of Molecular Biology (Faculty of Science and Technology).
    Stahls, Gunilla
    The genetic population structure of lotic and lentic mayflies of the Baetis vernus group (Ephemeroptera: Baetidae)2012In: Canadian Entomologist, ISSN 0008-347X, E-ISSN 1918-3240, Vol. 144, no 5, p. 679-690Article in journal (Refereed)
    Abstract [en]

    Nymphs of lotic mayflies live in environments that are expected to give rise to different degrees of population structuring. Here we investigate two taxa adapted to different lifestyles. Baetis macani Kimmins (Ephemeroptera: Baetidae) lives in flowing water; brooks that may periodically dry out in the summer or freeze to the bottom in winter. Baetis jaervii Savolainen is mostly found in sedge belts along the shores of lakes. Most insects living in flowing water show low levels of among-population genetic differentiation within and among catchments. Levels of differentiation in the lotic species are therefore assumed to be lower than in lentic B. jaervii. Here we test this hypothesis. Mitochondrial DNA and allele frequencies of nuclear genes were used to detect population structure in specimens originating from an extensive area from northern Finland. The genetic differentiation among populations of the lotic B. macani is more than twice the corresponding value for the lentic B. jaervii (F-ST 0.33 versus 0.15, while the mean F-ST between species was 0.33 and significant). The result is congruent within the cytochrome c oxidase subunit I gene (COI) partial gene frequencies. We argue that the significant genetic population structure, which only was found in the lotic B. macani, is differentiated as a consequence to the unpredictable environment as contrasted to the stable environment in standing bodies of water.

  • 200. Du, Shuhui
    et al.
    Wang, Zhaoshan
    Ingvarsson, Pär K
    Umeå University, Faculty of Science and Technology, Department of Ecology and Environmental Sciences. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Wang, Dongsheng
    Wang, Junhui
    Wu, Zhiqiang
    Tembrock, Luke R.
    Zhang, Jianguo
    Multilocus analysis of nucleotide variation and speciation in three closely related Populus (Salicaceae) species2015In: Molecular Ecology, ISSN 0962-1083, E-ISSN 1365-294X, Vol. 24, no 19, p. 4994-5005Article in journal (Refereed)
    Abstract [en]

    Historical tectonism and climate oscillations can isolate and contract the geographical distributions of many plant species, and they are even known to trigger species divergence and ultimately speciation. Here, we estimated the nucleotide variation and speciation in three closely related Populus species, Populus tremuloides, P.tremula and P.davidiana, distributed in North America and Eurasia. We analysed the sequence variation in six single-copy nuclear loci and three chloroplast (cpDNA) fragments in 497 individuals sampled from 33 populations of these three species across their geographic distributions. These three Populus species harboured relatively high levels of nucleotide diversity and showed high levels of nucleotide differentiation. Phylogenetic analysis revealed that P.tremuloides diverged earlier than the other two species. The cpDNA haplotype network result clearly illustrated the dispersal route from North America to eastern Asia and then into Europe. Molecular dating results confirmed that the divergence of these three species coincided with the sundering of the Bering land bridge in the late Miocene and a rapid uplift of the Qinghai-Tibetan Plateau around the Miocene/Pliocene boundary. Vicariance-driven successful allopatric speciation resulting from historical tectonism and climate oscillations most likely played roles inthe formation of the disjunct distributions and divergence of these three Populus species.

1234567 151 - 200 of 982
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf