| 1. |
- Sanli, Kemal, et al.
(författare)
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Metagenomic Sequencing of Marine Periphyton: Taxonomic and Functional Insights into Biofilm Communities
- 2015
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Ingår i: Frontiers in Microbiology. - : Frontiers Media SA. - 1664-302X. ; 6:1192
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Tidskriftsartikel (refereegranskat)abstract
- Periphyton communities are complex phototrophic, multispecies biofilms that develop on surfaces in aquatic environments. These communities harbor a large diversity of organisms comprising viruses, bacteria, algae, fungi, protozoans and metazoans. However, thus far the total biodiversity of periphyton has not been described. In this study, we use metagenomics to characterize periphyton communities from the marine environment of the Swedish west coast. Although we found approximately ten times more eukaryotic rRNA marker gene sequences compared to prokaryotic, the whole metagenome-based similarity searches showed that bacteria constitute the most abundant phyla in these biofilms. We show that marine periphyton encompass a range of heterotrophic and phototrophic organisms. Heterotrophic bacteria, including the majority of proteobacterial clades and Bacteroidetes, and eukaryotic macro-invertebrates were found to dominate periphyton. The phototrophic groups comprise Cyanobacteria and the alpha-proteobacterial genus Roseobacter, followed by different micro- and macro-algae. We also assess the metabolic pathways that predispose these communities to an attached lifestyle. Functional indicators of the biofilm form of life in periphyton involve genes coding for enzymes that catalyze the production and degradation of extracellular polymeric substances, mainly in the form of complex sugars such as starch and glycogen-like meshes together with chitin. Genes for 278 different transporter proteins were detected in the metagenome, constituting the most abundant protein complexes. Finally, genes encoding enzymes that participate in anaerobic pathways, such as denitrification and methanogenesis, were detected suggesting the presence of anaerobic or low-oxygen micro-zones within the biofilms.
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| 2. |
- Shu, Nanjiang, 1981-
(författare)
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Prediction of zinc-binding sites in proteins and efficient protein structure description and comparison
- 2008
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- A large number of proteins require certain metals to stabilize their structures or to function properly. About one third of all proteins in the Protein Data Bank (PDB) contain metals and it is estimated that approximately the same proportion of all proteins are metalloproteins. Zinc, the second most abundant transition metal found in eukaryotic organisms, plays key roles, mainly structural and catalytic, in many biological functions. Predicting whether a protein binds zinc and even the accurate location of binding sites is important when investigating the function of an experimentally uncharacterized protein. Describing and comparing protein structures with both efficiency and accuracy are essential for systematic annotation of functional properties of proteins, be it on an individual or on a genome scale. Dozens of structure comparison methods have been developed in the past decades. In recent years, several research groups have endeavoured in developing methods for fast comparison of protein structures by representing the three-dimensional (3D) protein structures as one-dimensional (1D) geometrical strings based on the shape symbols of clustered regions of φ/ψ torsion angle pairs of the polypeptide backbones. These 1D geometrical strings, shape strings, are as compact as 1D secondary structures but carry more elaborate structural information in loop regions and thus are more suitable for fast structure database searching, classification of loop regions and evaluation of model structures. In this thesis, a new method for predicting zinc-binding sites in proteins from amino acid sequences is described. This method predicts zinc-binding Cys, His, Asp and Glu (the four most common zinc-binding residues) with 75% precision (86% for Cys and His only) at 50% recall according to a solid 5-fold cross-validation on a non-redundant set of the PDB chains containing 2727 unique chains, of which 235 bind to zinc. This method predicts zinc-binding Cys and His with about 10% higher precision at different recall levels compared to a previously published method. In addition, different methods for describing and comparing protein structures are reviewed. Some recently developed methods based on 1D geometrical representation of backbone structures are emphasized and analyzed in details.
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| 3. |
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| 4. |
- Tedersoo, Leho, et al.
(författare)
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Novel soil-inhabiting clades fill gaps in the fungal tree of life
- 2017
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Ingår i: Microbiome. - : Springer Science and Business Media LLC. - 2049-2618. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- Background - Fungi are a diverse eukaryotic group of degraders, pathogens, and symbionts, with many lineages known only from DNA sequences in soil, sediments, air, and water. Results - We provide rough phylogenetic placement and principal niche analysis for >40 previously unrecognized fungal groups at the order and class level from global soil samples based on combined 18S (nSSU) and 28S (nLSU) rRNA gene sequences. Especially, Rozellomycota (Cryptomycota), Zygomycota s.lat, Ascomycota, and Basidiomycota are rich in novel fungal lineages, most of which exhibit distinct preferences for climate and soil pH. Conclusions - This study uncovers the great phylogenetic richness of previously unrecognized order- to phylum-level fungal lineages. Most of these rare groups are distributed in different ecosystems of the world but exhibit distinct ecological preferences for climate or soil pH. Across the fungal kingdom, tropical and non-tropical habitats are equally likely to harbor novel groups. We advocate that a combination of traditional and high-throughput sequencing methods enable efficient recovery and phylogenetic placement of such unknown taxonomic groups.
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| 5. |
- Hennerdal, Aron, et al.
(författare)
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Internal duplications in alpha-helical membrane protein topologies are common but the nonduplicated forms are rare
- 2010
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Ingår i: Protein Science. - : Wiley. - 0961-8368 .- 1469-896X. ; 19:12, s. 2305-2318
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Tidskriftsartikel (refereegranskat)abstract
- Many alpha-helical membrane proteins contain internal symmetries, indicating that they might have evolved through a gene duplication and fusion event Here, we have characterized internal duplications among membrane proteins of known structure and in three complete genomes We found that the majority of large transmembrane (TM) proteins contain an internal duplication The duplications found showed a large variability both in the number of TM-segments included and in their orientation Surprisingly, an approximately equal number of antiparallel duplications and parallel duplications were found However, of all 11 superfamilies with an internal duplication, only for one, the AcrB Multidrug Efflux Pump, the duplicated unit could be found in its nonduplicated form An evolutionary analysis of the AcrB homologs indicates that several independent fusions have occurred, including the fusion of the SecD and SecF proteins into the 12-TM-protein SecDF in Brucella and Staphylococcus aureus In one additional case, the Vitamin B-12 transporter-like ABC transporters, the protein had undergone an additional fusion to form protein with 20 TM-helices in several bacterial genomes Finally, homologs to all human membrane proteins were used to detect the presence of duplicated and nonduplicated proteins This confirmed that only in rare cases can homologs with different duplication status be found, although internal symmetry is frequent among these proteins One possible explanation is that it is frequent that duplication and fusion events happen simultaneously and that there is almost always a strong selective advantage for the fused form
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| 6. |
- Buckland, Philip I., 1973-, et al.
(författare)
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The Strategic Environmental Archaeology Database : a resource for international, multiproxy and transdisciplinary studies of environmental and climatic change
- 2015
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Konferensbidrag (refereegranskat)abstract
- Climate and environmental change are global challenges which require global data and infrastructure to investigate. These challenges also require a multi-proxy approach, integrating evidence from Quaternary science and archaeology with information from studies on modern ecology and physical processes among other disciplines. The Strategic Environmental Archaeology Database (SEAD http://www.sead.se) is a Swedish based international research e-infrastructure for storing, managing, analysing and disseminating palaeoenvironmental data from an almost unlimited number of analysis methods. The system currently makes available raw data from over 1500 sites (>5300 datasets) and the analysis of Quaternary fossil insects, plant macrofossils, pollen, geochemistry and sediment physical properties, dendrochronology and wood anatomy, ceramic geochemistry and bones, along with numerous dating methods. This capacity will be expanded in the near future to include isotopes, multi-spectral and archaeo-metalurgical data. SEAD also includes expandable climate and environment calibration datasets, a complete bibliography and extensive metadata and services for linking these data to other resources. All data is available as Open Access through http://qsead.sead.se and downloadable software. SEAD is maintained and managed at the Environmental Archaeology Lab and HUMlab at Umea University, Sweden. Development and data ingestion is progressing in cooperation with The Laboratory for Ceramic Research and the National Laboratory for Wood Anatomy and Dendrochronology at Lund University, Sweden, the Archaeological Research Laboratory, Stockholm University, the Geoarchaeological Laboratory, Swedish National Historical Museums Agency and several international partners and research projects. Current plans include expanding its capacity to serve as a data source for any system and integration with the Swedish National Heritage Board's information systems. SEAD is partnered with the Neotoma palaeoecology database (http://www.neotomadb.org) and a new initiative for building cyberinfrastructure for transdisciplinary research and visualization of the long-term human ecodynamics of the North Atlantic funded by the National Science Foundation (NSF).
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| 7. |
- Alm Rosenblad, Magnus, 1957, et al.
(författare)
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Detection of signal recognition particle (SRP) RNAs in the nuclear ribosomal internal transcribed spacer 1 (ITS1) of three lineages of ectomycorrhizal fungi (Agaricomycetes, Basidiomycota)
- 2016
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Ingår i: MycoKeys. - : Pensoft Publishers. - 1314-4057 .- 1314-4049. ; 13, s. 21-33
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Tidskriftsartikel (refereegranskat)abstract
- During a routine scan for Signal Recognition Particle (SRP) RNAs in eukaryotic sequences, we surprisingly found in silico evidence in GenBank for a 265-base long SRP RNA sequence in the ITS1 region of a total of 11 fully identified species in three ectomycorrhizal genera of the Basidiomycota (Fungi): Astraeus, Russula, and Lactarius. To rule out sequence artifacts, one specimen from a species indicated to have the SRP RNA-containing ITS region in each of these genera was ordered and re-sequenced. Sequences identical to the corresponding GenBank entries were recovered, or in the case of a non-original but conspecific specimen differed by three bases, showing that these species indeed have an SRP RNA sequence incorporated into their ITS1 region. Other than the ribosomal genes, this is the first known case of non-coding RNAs in the eukaryotic ITS region, and it may assist in the examination of other types of insertions in fungal genomes.
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| 8. |
- Mishra, Laxmi S., 1983-
(författare)
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FtsH metalloproteases and their pseudo-proteases in the chloroplast envelope of Arabidopsis thaliana
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- By cleaving peptide bonds, proteases either activate or degrade proteins and maintain protein quality control in response to various developmental stimuli and environmental factors. My work has focused on elucidating the role of the filamentation temperature sensitive protein H (FtsH) proteases. FtsHs belong to a membrane-embedded class of proteases found in eubacteria, animals and plants, which are located in the organelles of endosymbiosis (mitochondria and chloroplasts). They possess an AAA+ (ATPase associated with various cellular activities) and a peptidase M41 domain containing the HEXXH consensus sequence in the Zn2+ metalloprotease domain. FtsH proteases are known to form ring-like homo- or hetero-hexameric complexes. Arabidopsis thaliana, the model plant used in this study, contains seventeen AtFtsH proteases, of which twelve are presumably proteolytically active and five presumably proteolytic inactive members, known as AtFtsHi (i for inactive). In AtFtsHi members, the HEXXH motif is either deleted (AtFtsHi3) or mutated (AtFtsHi1, 2, 4, 5). Twelve AtFtsHs (AtFtsH 1, 2, 5–9, 11, 12 and AtFtsHi 1-5) are targeted to the chloroplast, whereas the remaining three (AtFtsH 3, 4 and 10) are mitochondrial. In Paper I, we demonstrate that AtFtsH12 interacts with AtFtsHi1, 2, 4, 5 to form a heteromeric complex. Abundance of these AtFtsH12-AtFtsHi complexes alters the accumulation of TIC (translocon on the inner chloroplast membrane) complexes. Transgenic mi12 (miRNA) knockdown plants that express lower amounts of AtFtsH12 displayed a pale-seedling and an aberrant chloroplast phenotype. mi12 plants displayed lowered total chlorophyll (Chla+Chlb) amount compared to wild type (WT), complementation lines and native AtFtsH12 promoter overexpressor (ox12) lines. Our biochemical studies identified drastic modifications in the total proteome of mi12 seedlings. N-terminome analyses of mi12 seedlings showed undisturbed plastidic protein maturation. In Paper II, we have shown that single mutants depleted in AtFTSHI1, 2, 4 or 5 are embryo-lethal, suggesting the pseudo-proteases to have an indispensable role in seed germination. This study further identified “weak” Atftshi1, Atftshi4, Atftshi3-1(kd) and Atftshi3-2 homozygous mutants, which develop into plants with altered photosynthetic efficiency. Field experiments were performed to determine the Darwinian fitness of these homozygous as well as heterozygous AtFtsHi mutants. The results suggested AtFtsHi enzymes to be critical during early developmental stages. A complete Atftshi3 knockdown mutant (Atftshi3-1(kd)) was identified (described in Paper III), which is not embryo-lethal and tolerates drought better than WT plants. Atftshi3-1(kd) leaves were smaller with fewer and smaller stomatal aperture. Above ground, Atftshi3-1(kd) leaves displayed lowered stomatal conductance and increased WUEi (intrinsic water-use efficiency), while below ground, the root-associated bacterial community showed a typical drought stress response. Upregulated transcripts of the ABA-responsive genes in leaves of Atftshi3-1(kd) compared to WT indicate the drought tolerance to be controlled independently of ABA. To conclude, AtFtsHi pseudo-proteases affect various stages of plant development and abiotic stress management, especially drought.
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| 9. |
- Sigvald, Roland, et al.
(författare)
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Molecular identification of bloodmeals and species composition in Culicoides biting midges
- 2013
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Ingår i: Medical and Veterinary Entomology. - : Wiley. - 0269-283X .- 1365-2915. ; 27, s. 104-112
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Tidskriftsartikel (refereegranskat)abstract
- Investigations of host preferences in haematophagous insects, including Culicoides biting midges (Diptera: Ceratopogonidae), are critical in order to assess transmission routes of vector-borne diseases. In this study, we collected and morphologically identified 164 blood-engorged Culicoides females caught in both light traps and permanent 12-m high suction traps during 20082010 in Sweden. Molecular analysis of the mitochondrial cytochrome c oxidase subunit I (COI) gene in the biting midges was performed to verify species classification, discern phylogenetic relationships and uncover possible cryptic species. Bloodmeal analysis using universal vertebrate cytochrome b primers revealed a clear distinction in host selection between mammalophilic and ornithophilic Culicoides species. Host sequences found matches in horse (n = 59), sheep (n = 39), cattle (n = 26), Eurasian elk (n = 1) and 10 different bird species (n = 18). We identified 15 Culicoides species previously recorded in Scandinavia and four additional species haplotypes that were distinctly different from the described species. All ornithophilic individuals (n = 23) were caught exclusively in the suction traps, as were, interestingly, almost all mammalophilic species (n = 41), indicating that many biting midge species may be able to cover long distances after completing a bloodmeal. These results add new information on the composition of Culicoides species and their host preferences and their potential long-distance dispersal while blood-engorged.
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| 10. |
- Ihse, Elisabet, 1977-, et al.
(författare)
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Amyloid fibrils with fragmented ATTR may be the rule in non-Val30Met ATTR amyloidosis
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The clinical phenotype of familial ATTR amyloidosis depends to some extent on the particular mutation, but differences exist also within mutations. We have previously described that two types of amyloid fibril compositions exist among Swedish ATTRV30M amyloidosis patients, one consisting of a mixture of intact and fragmented ATTR (type A) and one composed of only intact ATTR (type B). Patients with type A fibrils have a late age of onset and signs of cardiomyopathy, while patients with type B fibrils have an early onset and much less myocardial involvement. The present study aimed to determine if the correlation between fibril type and clinical phenotype is true for familial amyloidosis in general. Cardiac and/or adipose tissue from 48 patients carrying 21 different non-TTRV30M mutations were examined, as well as 7 non-Swedish ATTRV30M patients. Fibril type was determined with western blotting and compared to the patients´ age of onset and degree of cardiomyopathy. Non-Swedish V30M patients showed the same correlation as described for Swedish V30M patients, with fibrils of only full-length ATTR (type B) linked to less myocardial involvement. In contrast, all patients with non-V30M mutations had a fibril composition with ATTR fragments (type A). Some of these patients had onset of disease at young age. The vast majority had increased thickness of left cardiac ventricle, but a few individuals had values within normal limits. This study shows that a fibril composition with fragmented ATTR is very common in ATTR amyloidosis. It also suggests that fibrils composed of only full-length ATTR is an exception, perhaps only found among young ATTRV30M amyloidosis patients.
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| 11. |
- Ihse, Elisabet, 1977-
(författare)
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Two Types of Fibrils in ATTR Amyloidosis : Implications for Clinical Phenotype and Treatment Outcome
- 2011
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Systemic amyloidoses are a group of lethal diseases where proteins aggregate into fibrillar structures, called amyloid fibrils, that deposits throughout the body. Transthyretin (TTR) causes one type of amyloidosis, in which the aggregates mainly infiltrate nervous and cardiac tissue. Almost a hundred different mutations in the TTR gene are known to trigger the disease, but wild-type (wt) TTR is also incorporated into the fibrils, and may alone form amyloid. Patients with the TTRV30M mutation show, for unknown reasons, two clinical phenotypes. Some have an early onset of disease without cardiomyopathy while others have a late onset and cardiomyopathy. It has previously been described that amyloid fibrils formed from TTRV30M can have two different compositions; either with truncated molecules beside full-length TTR (type A) or only-full-length molecules (type B). In this thesis, the clinical importance of the two types of amyloid fibrils was investigated. We found that the fibril composition types are correlated to the two clinical phenotypes seen among TTRV30M patients, with type A fibrils present in late onset patients and type B fibrils in early onset patients. The only treatment for hereditary TTR amyloidosis has been liver transplantation, whereby the liver producing the mutant TTR is replaced by an organ only producing wt protein. However, in some patients, cardiac symptoms progress post-transplantationally. We demonstrated that the propensity to incorporate wtTTR differs between fibril types and tissue types in TTRV30M patients, with cardiac amyloid of type A having the highest tendency. This offers an explanation to why particularly cardiac amyloidosis develops after transplantation, and suggests which patients that are at risk for such development. By examining patients with other mutations than TTRV30M, we showed that, in contrast to the general belief, a fibril composition with truncated TTR is very common and might even be the general rule. This may explain why TTRV30M patients often have a better outcome after liver transplantation than patients with other mutations. In conclusion, this thesis has contributed with one piece to the puzzle of understanding the differences in clinical phenotype and treatment response between TTR amyloidosis patients, by demonstrating corresponding differences at a molecular level.
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| 12. |
- Alfredsson Timmins, Jenny, 1976-
(författare)
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Functional organisation of the cell nucleus in the fission yeast, Schizosaccharomyces pombe
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In eukaryotes the genome adopts a non-random spatial organisation, which is important for gene regulation. However, very little is known about the driving forces behind nuclear organisation. In the simple model eukaryote fission yeast, Schizosaccharomyces pombe, it has been known for a long time that transcriptionally repressed heterochromatin localise to the nuclear membrane (NM); the centromeres attaches to spindle pole body (SPB), while the telomeres are positioned at the NM on the opposite side of the nucleus compared to the SPB. Studies presented in this thesis aimed at advancing our knowledge of nuclear organisation in Schizosaccharomyces pombe. We show that the heterochromatic mating-type region localises to the NM in the vicinity of the SPB. This positioning was completely dependent on Clr4, a histone methyl transferase crucial for the formation of heterochromatin. Additional factors important for localisation were also identified: the chromo domain protein Swi6, and the two boundary elements IR-L and IR-R surrounding this locus. We further identify two other chromo domain proteins; Chp1 and Chp2, as crucial factors for correct subnuclear localisation of this region. From these results we suggest that the boundary elements together with chromodomain proteins in balanced dosage and composition cooperate in organising the mating-type chromatin. Gene regulation can affect the subnuclear localisation of genes. Using nitrogen starvation in S. pombe as a model for gene induction we determined the subnuclear localisation of two gene clusters repressed by nitrogen: Chr1 and Tel1. When repressed these loci localise to the NM, and this positioning is dependent on the histone deacetylase Clr3. During induction the gene clusters moved towards the nuclear interior in a transcription dependent manner. The knowledge gained from work presented in this thesis, regarding nuclear organisation in the S. pombe model system, can hopefully aid to a better understanding of human nuclear organisation.
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| 13. |
- Bag, Pushan, 1993-
(författare)
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How could Christmas trees remain evergreen? : photosynthetic acclimation of Scots pine and Norway spruce needles during winter
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Plants and other green organisms harvest sunlight by green chlorophyll pigments and covertit to chemical energy (sugars) and oxygen in a process called photosynthesis providing the foundation for life on Earth. Although it is unanimously believed that oceanic phytoplanktons are the main contributors to the global photosynthesis, the contribution of coniferous boreal forests distributed across vast regions of the northern hemisphere cannot be undermined. Hence boreal forests account signifificantly for social, economical and environmental sustainability. Not only do conifers thrive in the tundra regions with extreme climate, but they also maintain their needles green over the boreal winter. A question remains; what makes them so resilient? In this respect, we aimed to understand the remarkable winter adaptation strategies in two dominant boreal coniferous species,i.e., Pinus sylvestris and Picea abies. First, we mapped the transcriptional landscape in Norway spruce (Picea abies) needles over the annual cycle. Transcriptional changes in the nascent needles reflflected a sequence of developmental processes and active vegetative growth during early summer and summer. Later after maturation, transcriptome reflflected activated defense against biotic factors and acclimationin response to abiotic environmental cues such as freezing temperatures during winter. Secondly, by monitoring the photosynthetic performance of Scot pine needles, we found that the trees face extreme stress during the early spring (Feb-Mar) when sub-zero temperatures are accompanied by high solar radiation. At this time, drastic changes occur in the thylakoid membranes of the chloroplast that allows the mixing of photosystem I and photosystem II that typically remain laterally segregated. This triggers direct energy transfer from PSII to PSI and thus protects PSII from damage. Furthermore, we found that this loss of lateral segregation may be a consequence of triple phosphorylationof Lhcb1 (Light harvesting complex1 of photosystem II). The structural changes in thylakoid membranes also lead to changes inthe thylakoid macro domain organisationand pigment protein composition. Furthermore, we discovered that while PSII is protected by direct energy transfer, the protection of PSI is provided through photoreduction of oxygen by flavodiiron proteins, which in turn allows P700 to stay in an oxidised state necessary for direct energy transfer. These coordinated cascades of changes concomitantly protect both PSI and PSII to maintain the needles green over the winter.
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| 14. |
- Cheung, Henry Lok Shan, et al.
(författare)
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Denitrification, anammox, and DNRA in oligotrophic continental shelf sediments
- 2024
-
Ingår i: Limnology and Oceanography. - 1939-5590 .- 0024-3590.
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Tidskriftsartikel (refereegranskat)abstract
- Continental shelf sediments are considered hotspots for nitrogen (N) removal. While most investigations have quantified denitrification in shelves receiving large amounts of anthropogenic nutrient supply, we lack insight into the key drivers of N removal on oligotrophic shelves. Here, we measured rates of N removal through denitrification and anammox by the revised-isotope pairing technique (r-IPT) along the Northeastern New Zealand shelf. Denitrification dominated total N2 production at depths between 30 and 128 m with average rates (± SE) ranging from 65 ± 28 to 284 ± 72 μmol N m−2 d−1. N2 production by anammox ranged from 3 ± 1 to 28 ± 11 μmol N m−2 d−1 and accounted for 2–19% of total N2 production. DNRA was negligible in these oligotrophic settings. Parallel microbial community analysis showed that both Proteobacteria and Planctomycetota were key taxa driving denitrification. Denitrification displayed a negative correlation with oxygen penetration depth, and a positive correlation with macrofauna abundance. Our denitrification rates were comparable to oligotrophic shelves from the Arctic, but were lower than those from nutrient-rich Pacific and Atlantic shelves. Based on our results and existing IPT measurements, the global shelf denitrification rate was reassessed to be 53.5 ± 8.1 Tg N yr−1, equivalent to 20 ± 2% of marine N removal. We suggest that previous estimates of global shelf N loss might have been overestimated due to sampling bias toward areas with high N loads in the Northern Hemisphere.
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| 15. |
- Janzon, Anders, 1978, et al.
(författare)
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Exploring the microbial resistome in river sediments exposed to extraordinary high levels of antibiotics
- 2010
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Ingår i: 35th FEBS Congress: Molecules of Life.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The rapid development and propagation of antibiotic resistance in pathogenic and opportunistic bacteria is a major threat to public health worldwide. The phenomenon has been widely studied in the clinical setting, but comparatively little is known about the prevalence and diversity of antibiotic resistance in communities of environmental bacteria, often referred to as the environmental resistome. As the external environment may function as a reservoir of resistance genes to human pathogens, we are interested in how environmental bacteria are affected by antibiotic pollution. We have previously isolated microbial DNA from river sediments taken up- and downstream from a water treatment plant that processes waste water from several pharmaceutical plants producing antibiotics. In a previous study, we used deep sequencing to identify unprecedented frequencies of known resistance genes to several classes of antibiotics in these samples. In this study, we aim to functionally characterize the resistome in a more open and exploratory way by screening genomic DNA libraries transformed into sensitive hosts. To generate the libraries, several experimental strategies were explored, including mechanical shearing and enzymatic digestion of the isolated DNA followed by blunt- or sticky end cloning into different plasmids, subsequently transformed into sensitive E. coli. Pros and cons of the different strategies will be discussed along with preliminary results of the screening against selected antibiotics.
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| 16. |
- Klevebring, Daniel, 1981-
(författare)
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On Transcriptome Sequencing
- 2009
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis is about the use of massive DNA sequencing to investigate the transcriptome. During recent decades, several studies have made it clear that the transcriptome comprises a more complex set of biochemical machinery than was previously believed. The majority of the genome can be expressed as transcripts; and overlapping and antisense transcription is widespread. New technologies for the interroga- tion of nucleic acids have made it possible to investigate such cellular phenomena in much greater detail than ever before. For each application, special requirements need to be met. The work presented in this thesis focuses on the transcrip- tome and the development of technology for its analysis. In paper I, we report our development of an automated approach for sample preparation. The procedure was benchmarked against a publicly available reference data set, and we note that our approach outperformed similar manual procedures in terms of reproducibility. In the work reported in papers II-IV, we used different massive sequencing technologies to investigate the transcriptome. In paper II we describe a concatemerization approach that increased throughput by 65% using 454 sequencing,and we identify classes of transcripts not previously described in Populus. Papers III and IV both report studies based on SOLiD sequencing. In the former, we investigated transcripts and proteins for 13% of the human gene and detected a massive overlap for the upper 50% transcriptional levels. In the work described in paper IV, we investigated transcription in non-genic regions of the genome and detected expression from a high number of previ- ously unknown loci.
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| 17. |
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| 18. |
- Wikström, P, et al.
(författare)
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The regulatory N-terminal region of the aromatic-responsive transcriptional activator DmpR constrains nucleotide-triggered multimerisation.
- 2001
-
Ingår i: Journal of Molecular Biology. - : Elsevier BV. - 0022-2836 .- 1089-8638. ; 314:5
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Tidskriftsartikel (refereegranskat)abstract
- The transcriptional promoting activity of DmpR is under the strict control of its aromatic effector ligands that are bound by its regulatory N-terminal domain. The positive control function of DmpR resides within the central C-domain that is highly conserved among activators of sigma(54)-RNA polymerase. The C-domain mediates ATP hydrolysis and interaction with sigma(54)-RNA polymerase that are essential for open-complex formation and thus initiation of transcription. Wild-type and loss-of-function derivatives of DmpR, which are defective in distinct steps in nucleotide catalysis, were used to address the consequences of nucleotide binding and hydrolysis with respect to the multimeric state of DmpR and its ability to promote in vitro transcription. Here, we show that DmpR derivatives deleted of the regulatory N-terminal domain undergo an aromatic-effector independent ATP-binding triggered multimerisation as detected by cross-linking. In the intact protein, however, aromatic effector activation is required before ATP-binding can trigger an apparent dimer-to-hexamer switch in subunit conformation. The data suggest a model in which the N-terminal domain controls the transcriptional promoting property of DmpR by constraining ATP-mediated changes in its oligomeric state. The results are discussed in the light of recent mechanistic insights from the AAA(+) superfamily of ATPases that utilise nucleotide hydrolysis to restructure their substrates.
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| 19. |
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| 20. |
- Mamontov, Eugen, 1955
(författare)
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Homeorhesis and evolutionary properties of living systems: From ordinary differential equations to the active-particle generalized kinetics theory
- 2006
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Ingår i: 10th Evolutionary Biology Meeting at Marseilles, 20-22 September 2006, Marseilles, France.
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Konferensbidrag (refereegranskat)abstract
- Advanced generalized-kinetic-theory (GKT) models for biological systems are developed for populations of active (or living) particles [1]-[5]. These particles are described with both the stochastic variables common in kinetic theory (such as time, the particle random location and velocity) and the stochastic variables related to the internal states of an active particle. Evolution of these states represents biological, ecological, or social properties of the particle behavior. Paper [6] analyzes a number of the well-known statistical-mechanics approaches and shows that the active-particle GKT (APGKT) is the only treatment capable of modelling living systems. Work [2] summarizes the significance of the notion of an active particle in kinetic models. This notion draws attention to the features distinguishing living matter from nonliving matter. They are discussed by many authors (e.g., [7]-[15], [1]-[3], [6], [16]-[18]). Work [11] considers a lot of differences between living and nonliving matters, and the limitations of the modelling approaches developed for nonliving matter. Work [6] mainly focuses on the comparison of a few theoretical mechanics treatments in terms of the key living-matter properties formulated in [15]. One of the necessary properties of the evolution of living systems is homeorhesis. It is, loosely speaking, a peculiar qualitative and quantitative insensitivity of a living system to the exogenous signals acting on it. The earlier notion, homeostasis, was introduced by W. B. Cannon in 1926 who discussed the phenomenon in detail later [7]. Homeorhesis introduced by C. H. Waddington [8, p. 32] generalizes homeostasis and is well known in biology [8], [9], [12]. It is an inherent part of mathematical models for oncogeny (e.g., [16]-[18], [6, Appendix]). Homeorhesis is also discussed in [3, Section 4] in connection with APGKT. Homeorhesis is documented in ecology (e.g., [11], [13, the left column on p. 675]) where it is one of the key notions of the strong Gaia theory, a version of the Gaia theory (e.g., [14, Chapter 8]). The strong Gaia theory “states that the planet with its life, a single living system, is regulated in certain aspects by that life” [14, p. 124]. The very origin of the name “Gaia” is related to homeorhesis or homeostasis [14, p. 118]. These notions are also used in psychology and sociology. If evolution of a system is not homeorhetic, the system can not be living. Work [6, Appendix] derives a preliminary mathematical formulation of homeorhesis in terms of the simplest dynamical systems, i.e. ordinary differential equations (ODEs). The present work complements, extended, and further specify the approach of [6, Appendix]. The work comprises the two main parts. The first part develops the sufficient conditions for ODE systems to describe homeorhesis, and suggests a fairly general structure of the ODE model. It regards homeorhesis as piecewise homeostasis. The model can be specified in different ways depending on specific systems and specific purposes of the analysis. An example of the specification is also noted (the PhasTraM nonlinear reaction-diffusion model for hyperplastic oncogeny [16]-[18]). The second part of the work discusses implementation of the above homeorhesis ODE model in terms of a special version [3] of APGKT (see above). The key feature of this version is that the components of a living population need not be discrete: the subdivision into the components is described with a general, continuous-discrete probability distribution (see also [6]). This enables certain properties of living matter noted in [15]. Moreover, the corresponding APGKT model presents a system of, firstly, a generalized kinetic equation for the conditional distribution function conditioned by the internal states of the population and, secondly, Ito's stochastic differential equations for these states. This treatement employs the results on nonstationary invariant diffusion stochastic processes [19]. The second part of the work also stresses that APGKT is substantially more important for the living-matter analysis than in the case of nonliving matter. One of the reasons is certain limitations in experimental sampling of the living-system modes presented with stochastic processes. A few directions for future research are suggested as well. REFERENCES: [1] Bellomo, N., Bellouquid, A. and Delitala, M., 2004, Mathematical topics on the modelling complex multicellular systems and tumor immune cells competition, Math. Models Methods Appl. Sci., 14, 1683-1733. [2] Bellomo, N., 2006, New hot Paper Comments, Essential Science Indicators, http://www.esi-topics.com/nhp/2006 /may- 06-NicolaBellomo.html. [3] Willander, M., Mamontov, E. and Chiragwandi, Z., 2004, Modelling living fluids with the subdivision into the components in terms of probability distributions, Math. Models Methods Appl. Sci. 14, 1495-1520. [4] Bellomo, N. and Maini, P.K., 2005, Preface and the Special Issue “Multiscale Cancer Modelling-A New Frontier in Applied Mathematics”, Math. Models Methods Appl. Sci., 15, iii-viii. [5] De Angelis, E. and Delitala, M., 2006, Modelling complex systems in applied sciences: Methods and tools of the mathematical kinetic theory for active particles. Mathl Comput. Modelling, 43, 1310-1328. [6] Mamontov, E., Psiuk-Maksymowicz, K. and Koptioug, A., 2006, Stochastic mechanics in the context of the properties of living systems, Mathl Comput. Modelling, Article in Press, 13 pp. [7] Cannon, W.B., 1932, The Wisdom of the Body (New York: Norton). [8] Waddington, C.H., 1957, The Strategy of the Genes. A Discussion of Some Aspects of Theoretical Biology (London, George Allen and Unwin). [9] Waddington, C.H., 1968, Towards a theoretical biology, Nature, 218, 525-527. [10] Cotnoir, P.-A., 1981, La compétence environnementale: Une affaire d’adaptation. Séminaire en écologie behaviorale, Univeristé du Québec, Montralé. Available online at: http://pac.cam.org/culture.doc . [11] O’Neill, R.V., DeAngelis, D.L., Waide, J.B. and Allen, T.F.H., 1986, A Hierarchical Concept of Ecosystems, Princeton: Princeton Univ. Press). [12] Sauvant, D., 1992, La modélisation systémique en nutrition, Reprod. Nutr. Dev., 32, 217-230. [13] Christensen, N.L., Bartuska, A.M., Brown, J.H., Carpenter, S., D'Antonio, C., Francis, R., Franklin, J.F., MacMahon, J.A., Noss, R.F., Parsons, D.J., Peterson, C.H., Turner, M.G. and Woodmansee, R.G., 1996, The Report of the Ecological Society of America Committee on the Scientific Basis for Ecosystem Management, Ecological Applications, 6, 665-691. Available online at: http://www.esa.org/pao/esaPositions/Papers/ReportOfSBEM.php. [14] Margulis, L., 1998, Symbiotic Planet. A New Look at Evolution (Amherst: Sciencewriters). [15] Hartwell, L.H., Hopfield, J.J., Leibler, S. and Murray, A.W., 1999, From molecular to modular cell biology, Nature, 402, C47-C52. [16] Mamontov, E., Koptioug, A.V. and Psiuk-Maksymowicz, K., 2006, The minimal, phase-transition model for the cell- number maintenance by the hyperplasia-extended homeorhesis, Acta Biotheoretica, 54, 44 pp., (no. 2, May-June, accepted). [17] Psiuk-Maksymowicz, K. and Mamontov, E., 2005, The time-slices method for rapid solving the Cauchy problem for nonlinear reaction-diffusion equations in the competition of homeorhesis with genotoxically activated hyperplasia, In: European Conference on Mathematical and Theoretical Biology - ECMTB05 (July 18-22, 2005) Book of Abstracts, Vol.1 (Dresden: Center for Information Services and High Performance Computing, Dresden Univ. Technol.), p. 429 (http://www.ecmtb05.org/). [18] Psiuk-Maksymowicz, K. and Mamontov, E., 2006, The homeorhesis-based modelling and fast numerical analysis for oncogenic hyperplasia under radiation therapy, submitted. [19] Mamontov, E., 2005, Nonstationary invariant distributions and the hydrodynamic-style generalization of the Kolmogorov-forward/Fokker-Planck equation, Appl. Math. Lett. 18 (9) 976-982.
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| 21. |
- Zhang, Feng'e, et al.
(författare)
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Cell cycle-related lncRNAs and mRNAs in osteoarthritis chondrocytes in a Northwest Chinese Han Population
- 2020
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Ingår i: Medicine. - : Lippincott Williams & Wilkins. - 0025-7974 .- 1536-5964. ; 99:24
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Tidskriftsartikel (refereegranskat)abstract
- Background: A group of differentially expressed long non-coding RNAs (lncRNAs) have been shown to play key roles in osteoarthritis (OA), although they represented only a small proportion of lncRNAs that may be biologically and physiologically relevant. Since our knowledge of regulatory functions of non-coding RNAs is still limited, it is important to gain better understanding of their relation to the pathogenesis of OA.Methods: We performed mRNA and lncRNA microarray analysis to detect differentially expressed RNAs in chondrocytes from three OA patients compared with four healthy controls. Then, enrichment analysis of the differentially expressed mRNAs was carried out to define disease molecular networks, pathways and gene ontology (GO) function. Furthermore, target gene prediction based on the co-expression network was performed to reveal the potential relationships between lncRNAs and mRNAs, contributing an exploration of a role of lncRNAs in OA mechanism. Quantitative RT-PCR analyses were used to demonstrate the reliability of the experimental results.Findings: Altogether 990 lncRNAs (666 up-regulated and 324 down-regulated) and 546 mRNAs (419 up-regulated and 127 down-regulated) were differentially expressed in OA samples compared with the normal ones. The enrichment analysis revealed a set of genes involved in cell cycle. In total, 854 pairs of mRNA and lncRNA were highly linked, and further target prediction appointed 12 genes specifically for their corresponding lncRNAs. The lncRNAs lncRNA-CTD-2184D3.4, ENST00000564198.1, and ENST00000520562.1 were predicted to regulate SPC24, GALM, and ZNF345 mRNA expressions in OA.Interpretation: This study uncovered several novel genes potentially important in pathogenesis of OA, and forecast the potential function of lnc-CTD-2184D3.4, especially for the cell cycle in the chondrocytes. These findings may promote additional aspects in studies of OA.
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| 22. |
- Zhou, Tuping, et al.
(författare)
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A Novel Method for Accurate One-dimensional Protein Structure Prediction Based on Fragment Matching
- 2010
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Ingår i: Bioinformatics. - : Oxford University Press (OUP). - 1367-4803 .- 1367-4811. ; 26:4, s. 470-477
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Tidskriftsartikel (refereegranskat)abstract
- Motivation: The precise prediction of one-dimensional (1D) protein structure as represented by the protein secondary structure and 1D string of discrete state of dihedral angles (i.e. Shape Strings) is a prerequisite for the successful prediction of three-dimensional (3D) structure as well as protein-protein interaction. We have developed a novel 1D structure prediction method, called Frag1D, based on a straightforward fragment matching algorithm and demonstrated its success in the prediction of three sets of 1D structural alphabets, i.e. the classical three-state secondary structure, three-state Shape Strings and eight-state Shape Strings. Results: By exploiting the vast protein sequence and protein structure data available, we have brought secondary structure prediction closer to the expected theoretical limit. When tested by a leave-one-out cross validation on a non-redundant set of PDB cutting at 30% sequence identity containing 5860 protein chains, the overall per-residue accuracy for secondary structure prediction, i.e. Q3 is 82.9%. The overall per-residue accuracy for three-state and eight-state Shape Strings are 85.1% and 71.5% respectively. We have also benchmarked our program with the latest version of PSIPRED for secondary structure prediction and our program predicted 0.3% better in Q3 when tested on 2241 chains with the same training set. For Shape Strings, we compared our method with a recently published method with the same dataset and definition as used by that method. Our program predicted at 2.2% better in accuracy for three-state Shape Strings. By quantitatively investigating the effect of data base size on 1D structure prediction we show that the accuracy increases by about 1% with every doubling of the database size.
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| 23. |
- Eriksson, Martin, 1970, et al.
(författare)
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Triclosan changes community composition and selects for specific bacterial taxa in marine periphyton biofilms in low nanomolar concentrations
- 2020
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Ingår i: Ecotoxicology. - : Springer Science and Business Media LLC. - 0963-9292 .- 1573-3017. ; 29:7, s. 1083-1094
-
Tidskriftsartikel (refereegranskat)abstract
- The antibacterial agent Triclosan (TCS) is a ubiquitous environmental contaminant due to its widespread use. Sensitivity to TCS varies substantially among eu- and pro-karyotic species and its risk for the marine environment remains to be better elucidated. In particular, the effects that TCS causes on marine microbial communities are largely unknown. In this study we therefore used 16S amplicon rDNA sequencing to investigate TCS effects on the bacterial composition in marine periphyton communities that developed under long-term exposure to different TCS concentrations. Exposure to TCS resulted in clear changes in bacterial composition already at concentrations of 1 to 3.16 nM. We conclude that TCS affects the structure of the bacterial part of periphyton communities at concentrations that actually occur in the marine environment. Sensitive taxa, whose abundance decreased significantly with increasing TCS concentrations, include the Rhodobiaceae and Rhodobacteraceae families of Alphaproteobacteria, and unidentified members of the Candidate division Parcubacteria. Tolerant taxa, whose abundance increased significantly with higher TCS concentrations, include the families Erythrobacteraceae (Alphaproteobacteria), Flavobacteriaceae (Bacteroidetes), Bdellovibrionaceae (Deltaproteobacteria), several families of Gammaproteobacteria, and members of the Candidate phylum Gracilibacteria. Our results demonstrate the variability of TCS sensitivity among bacteria, and that TCS can change marine bacterial composition at concentrations that have been detected in the marine environment.
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| 24. |
- Saénz-de la O, Diana, et al.
(författare)
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Antioxidant and drought‑acclimation responses in UV‑B‑exposed transgenic Nicotiana tabacum displaying constitutive overproduction of H2O2
- 2023
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Ingår i: Photochemical and Photobiological Sciences. - : Springer. - 1474-905X .- 1474-9092. ; 22:10, s. 2373-2387
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Tidskriftsartikel (refereegranskat)abstract
- Hydrogen peroxide (H2O2) is an important molecule that regulates antioxidant responses that are crucial for plant stress resistance. Exposure to low levels of ultraviolet-B radiation (UV-B, 280–315 nm) can also activate antioxidant defenses and acclimation responses. However, how H2O2 and UV-B interact to promote stress acclimation remains poorly understood. In this work, a transgenic model of Nicotiana tabacum cv Xanthi nc, with elevated Mn-superoxide dismutase (Mn-SOD)activity, was used to study the interaction between the constitutive overproduction of H2O2 and a 14-day UV-B treatment (1.75 kJ m−2 d−1 biologically effective UV-B). Subsequently, these plants were subjected to a 7-day moderate drought treatment to evaluate the impact on drought resistance of H2O2- and UV-dependent stimulation of the plants' antioxidant system. The UV-B treatment enhanced H2O2 levels and altered the antioxidant status by increasing the epidermal flavonol index, Trolox Equivalent Antioxidant Capacity, and catalase, peroxidase and phenylalanine ammonia lyase activities in the leaves. UV-B also retarded growth and suppressed acclimation responses in highly H2O2-overproducing transgenic plants. Plants not exposed to UV-B had a higher drought resistance in the form of higher relative water content of leaves. Our data associate the interaction between Mn-SOD transgene overexpression and the UV-B treatment with a stress response. Finally, we propose a hormetic biphasic drought resistance response curve as a function of leaf H2O2 content in N. tabacum cv Xanthi.
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| 25. |
- Oelker, Melanie, 1988-
(författare)
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Disarming bacteria : a structure-based approach to design an anti-virulence drug against Listeria monocytogenes
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Antibiotic resistances are one of the biggest threats to global health and if we don’t change our behavior and way of using antibiotics we will end up in a ‘post-antibiotic era’, in which common infections and minor injuries can once kill again and up to 10 million deaths per year may occur by 2050. Therefore, there is a high need for new anti-bacterial drugs, especially of alternatives to existing antibiotics with already described resistances. Classical antibiotics target the essential processes of survival and growth in bacteria and therefore put a high selective pressure on them to develop resistances. In contrast, the ability to infect or damage a host, the virulence, is less essential for bacteria. Thus, targeting the virulence is supposed to cause a lower selective pressure and this alternative mode-of-action could help to decelerate the development of antibiotic resistances.The aims in this work were to proceed with the structure-based design of an anti-virulence drug against the food-borne pathogen Listeria monocytogenes, but also to deepen our understanding of the complex regulation system for the virulence of this bacterium. PrfA, the master regulator of virulence in Listeria monocytogenes, is a member of a large family of bacterial transcription factors, which are regulated by a conformational change and allosteric modulation by different regulator molecules. Furthermore, its critical role in virulence regulations makes is a suitable target for an anti-virulence drug. In this work new lead compounds based on the previously identified ring-fused 2-pyridone scaffold were designed, synthesized and analyzed by different biological, biophysical, computational and structural biology methods. Three new binding sites and binding modes of these compounds in PrfA were evaluated for their potential use in future designs and a compound with improved activity was identified. In a second study another structurally different lead compound was discovered to inhibit PrfA. Furthermore, the studies on proposed natural regulators of PrfA uncovered the underlying mechanism for the virulence regulation by the peptide signature of the environment and in a follow-up study the structural basis of the binding of inhibitory peptides to PrfA was further investigated. Finally, a structural review on all available structure of PrfA provided more insights into the allosteric regulation mechanism of PrfA activity.This work will hopefully support in the successful development of an anti-virulence drug against Listeria monocytogenes and thus contribute to the reduction of the problem of antibiotic resistances.
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