| 1. |
- Bengtsson-Palme, Johan, 1985, et al.
(author)
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Metaxa2 Database Builder: enabling taxonomic identification from metagenomic or metabarcoding data using any genetic marker
- 2018
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In: Bioinformatics (Oxford, England). - : Oxford University Press (OUP). - 1367-4811 .- 1367-4803. ; 34:23
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Journal article (peer-reviewed)abstract
- Correct taxonomic identification of DNA sequences is central to studies of biodiversity using both shotgun metagenomic and metabarcoding approaches. However, no genetic marker gives sufficient performance across all the biological kingdoms, hampering studies of taxonomic diversity in many groups of organisms. This has led to the adoption of a range of genetic markers for DNA metabarcoding. While many taxonomic classification software tools can be re-trained on these genetic markers, they are often designed with assumptions that impair their utility on genes other than the SSU and LSU rRNA. Here, we present an update to Metaxa2 that enables the use of any genetic marker for taxonomic classification of metagenome and amplicon sequence data.We evaluated the Metaxa2 Database Builder on eleven commonly used barcoding regions and found that while there are wide differences in performance between different genetic markers, our software performs satisfactorily provided that the input taxonomy and sequence data are of high quality.Freely available on the web as part of the Metaxa2 package at http://microbiology.se/software/metaxa2/.Supplementary data are available at Bioinformatics online.
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| 2. |
- Aurelius, Oskar, et al.
(author)
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The Crystal Structure of Thermotoga maritima Class III Ribonucleotide Reductase Lacks a Radical Cysteine Pre-Positioned in the Active Site
- 2015
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 10:7
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Journal article (peer-reviewed)abstract
- Ribonucleotide reductases (RNRs) catalyze the reduction of ribonucleotides to deoxyribonucleotides, the building blocks for DNA synthesis, and are found in all but a few organisms. RNRs use radical chemistry to catalyze the reduction reaction. Despite RNR having evolved several mechanisms for generation of different kinds of essential radicals across a large evolutionary time frame, this initial radical is normally always channelled to a strictly conserved cysteine residue directly adjacent to the substrate for initiation of substrate reduction, and this cysteine has been found in the structures of all RNRs solved to date. We present the crystal structure of an anaerobic RNR from the extreme thermophile Thermotoga maritima (tmNrdD), alone and in several complexes, including with the allosteric effector dATP and its cognate substrate CTP. In the crystal structure of the enzyme as purified, tmNrdD lacks a cysteine for radical transfer to the substrate pre-positioned in the active site. Nevertheless activity assays using anaerobic cell extracts from T. maritima demonstrate that the class III RNR is enzymatically active. Other genetic and microbiological evidence is summarized indicating that the enzyme is important for T. maritima. Mutation of either of two cysteine residues in a disordered loop far from the active site results in inactive enzyme. We discuss the possible mechanisms for radical initiation of substrate reduction given the collected evidence from the crystal structure, our activity assays and other published work. Taken together, the results suggest either that initiation of substrate reduction may involve unprecedented conformational changes in the enzyme to bring one of these cysteine residues to the expected position, or that alternative routes for initiation of the RNR reduction reaction may exist. Finally, we present a phylogenetic analysis showing that the structure of tmNrdD is representative of a new RNR subclass IIIh, present in all Thermotoga species plus a wider group of bacteria from the distantly related phyla Firmicutes, Bacteroidetes and Proteobacteria.
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| 3. |
- Balk, Lennart, et al.
(author)
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Widespread episodic thiamine deficiency in Northern Hemisphere wildlife
- 2016
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In: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 6
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Journal article (peer-reviewed)abstract
- Many wildlife populations are declining at rates higher than can be explained by known threats to biodiversity. Recently, thiamine (vitamin B-1) deficiency has emerged as a possible contributing cause. Here, thiamine status was systematically investigated in three animal classes: bivalves, ray-finned fishes, and birds. Thiamine diphosphate is required as a cofactor in at least five life-sustaining enzymes that are required for basic cellular metabolism. Analysis of different phosphorylated forms of thiamine, as well as of activities and amount of holoenzyme and apoenzyme forms of thiaminedependent enzymes, revealed episodically occurring thiamine deficiency in all three animal classes. These biochemical effects were also linked to secondary effects on growth, condition, liver size, blood chemistry and composition, histopathology, swimming behaviour and endurance, parasite infestation, and reproduction. It is unlikely that the thiamine deficiency is caused by impaired phosphorylation within the cells. Rather, the results point towards insufficient amounts of thiamine in the food. By investigating a large geographic area, by extending the focus from lethal to sublethal thiamine deficiency, and by linking biochemical alterations to secondary effects, we demonstrate that the problem of thiamine deficiency is considerably more widespread and severe than previously reported.
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| 4. |
- Jafari, Gholamali, et al.
(author)
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Genetics of extracellular matrix remodeling during organ growth using the Caenorhabditis elegans pharynx model.
- 2010
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In: Genetics. - : Oxford University Press (OUP). - 1943-2631. ; 186:3, s. 969-82
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Journal article (peer-reviewed)abstract
- The organs of animal embryos are typically covered with an extracellular matrix (ECM) that must be carefully remodeled as these organs enlarge during post-embryonic growth; otherwise, their shape and functions may be compromised. We previously described the twisting of the Caenorhabditis elegans pharynx (here called the Twp phenotype) as a quantitative mutant phenotype that worsens as that organ enlarges during growth. Mutations previously known to cause pharyngeal twist affect membrane proteins with large extracellular domains (DIG-1 and SAX-7), as well as a C. elegans septin (UNC-61). Here we show that two novel alleles of the C. elegans papilin gene, mig-6(et4) and mig-6(sa580), can also cause the Twp phenotype. We also show that overexpression of the ADAMTS protease gene mig-17 can suppress the pharyngeal twist in mig-6 mutants and identify several alleles of other ECM-related genes that can cause or influence the Twp phenotype, including alleles of fibulin (fbl-1), perlecan (unc-52), collagens (cle-1, dpy-7), laminins (lam-1, lam-3), one ADAM protease (sup-17), and one ADAMTS protease (adt-1). The Twp phenotype in C. elegans is easily monitored using light microscopy, is quantitative via measurements of the torsion angle, and reveals that ECM components, metalloproteinases, and ECM attachment molecules are important for this organ to retain its correct shape during post-embryonic growth. The Twp phenotype is therefore a promising experimental system to study ECM remodeling and diseases.
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| 5. |
- Estigoy, Colleen, et al.
(author)
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Intercalated discs : multiple proteins perform multiple functions in non-failing and failing human hearts
- 2009
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In: Biophysical Reviews. - : Springer Science and Business Media LLC. - 1867-2469 .- 1867-2450. ; 1:1, s. 43-49
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Journal article (peer-reviewed)abstract
- The intercalated disc (ICD) occupies a central position in the transmission of force, electrical continuity and chemical communication between cardiomyocytes. Changes in its structure and composition are strongly implicated in heart failure. ICD functions include: maintenance of electrical continuity across the ICD; physical links between membranes and the cytoskeleton; intercellular adhesion; maintenance of ICD structure and function; and growth. About 200 known proteins are associated with ICDs, 40% of which change in disease. We systemically reviewed cardiac immunohistochemical data on the Human Protein Atlas (HPA) web site, ExPASy protein binding data and published papers on ICDs. We identified 43 proteins not previously reported, and confirmed 37 proteins that have previously been described. In addition, 102 proteins not present on the HPA web site but were described in ICDs in the literature. We group these into clusters that demonstrate functionally interactive groups of proteins demonstrating that ICDs play a key role in cardiomyocyte function.
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| 6. |
- Langefors, Åsa, et al.
(author)
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Screening of Mhc variation in Atlantic salmon (Salmo salar) : a comparison of restriction fragment length polymorphism (RFLP), denaturing gradient gel electrophoresis (DGGE) and sequencing
- 2000
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In: Molecular Ecology. - : Wiley. - 0962-1083 .- 1365-294X. ; 9:2, s. 215-219
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Journal article (peer-reviewed)abstract
- We compared three different molecular methods currently used for screening of Mhc variation in population studies of Atlantic salmon. Restriction fragment length polymorphism (RFLP) of the entire class II gene detected 22 haplotypes. Seventeen exon 2 sequences were obtained from individuals carrying the 22 haplotypes, two of which had not been detected by RFLP. The six alleles (27%) detected by RFLP and not by exon 2 sequencing probably resulted from sequence variation outside exon 2. Within exon 2, RFLP differentiated 88% of the sequences. Alternatively, denaturing gradient gel electrophoresis (DGGE) performed under two run conditions detected 94% of the sequence variation. Both RFLP using different probes, and the two PCR-based methods using three different primer pairs, suggest that there is only a single Mhc class II B gene in the Baltic populations of Atlantic salmon.
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| 7. |
- Lohm, Jakob, et al.
(author)
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Experimental evidence for major histocompatibility complex-allele-specific resistance to a bacterial infection
- 2002
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In: Proceedings of the Royal Society of London. Biological Sciences. - : The Royal Society. - 0962-8452 .- 1471-2954. ; 269:1504, s. 2029-2033
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Journal article (peer-reviewed)abstract
- The extreme polymorphism found at some major histocompatibility complex (MHC) loci is believed to be maintained by balancing selection caused by infectious pathogens. Experimental support for this is inconclusive. We have studied the interaction between certain MHC alleles and the bacterium Aeromonas salmonicida, which causes the severe disease furunculosis, in Atlantic salmon (Salmo salar L.). We designed full-sibling broods consisting of combinations of homozygote and heterozygote genotypes with respect to resistance or susceptibility alleles. The juveniles were experimentally infected with A. salmonicida and their individual survival was monitored. By comparing full siblings carrying different MHC genotypes the effects on survival due to other segregating genes were minimized. We show that a pathogen has the potential to cause very intense selection pressure on particular MHC alleles; the relative fitness difference between individuals carrying different MHC alleles was as high as 0.5. A co-dominant pattern of disease resistance/susceptibility was found, indicative of qualitative difference in the immune response between individuals carrying the high- and low-resistance alleles. Rather unexpectedly, survival was not higher among heterozygous individuals as compared with homozygous ones.
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| 8. |
- Nystedt, Björn, et al.
(author)
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The Norway spruce genome sequence and conifer genome evolution
- 2013
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In: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 497:7451, s. 579-584
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Journal article (peer-reviewed)abstract
- Conifers have dominated forests for more than 200 million years and are of huge ecological and economic importance. Here we present the draft assembly of the 20-gigabase genome of Norway spruce (Picea abies), the first available for any gymnosperm. The number of well-supported genes (28,354) is similar to the >100 times smaller genome of Arabidopsis thaliana, and there is no evidence of a recent whole-genome duplication in the gymnosperm lineage. Instead, the large genome size seems to result from the slow and steady accumulation of a diverse set of long-terminal repeat transposable elements, possibly owing to the lack of an efficient elimination mechanism. Comparative sequencing of Pinus sylvestris, Abies sibirica, Juniperus communis, Taxus baccata and Gnetum gnemon reveals that the transposable element diversity is shared among extant conifers. Expression of 24-nucleotide small RNAs, previously implicated in transposable element silencing, is tissue-specific and much lower than in other plants. We further identify numerous long (>10,000 base pairs) introns, gene-like fragments, uncharacterized long non-coding RNAs and short RNAs. This opens up new genomic avenues for conifer forestry and breeding.
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| 9. |
- Singh, Umashankar, et al.
(author)
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Characterization of a novel obesity phenotype caused by interspecific hybridization.
- 2008
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In: Archives of Physiology and Biochemistry. - : Informa UK Limited. - 1381-3455 .- 1744-4160. ; 114:5, s. 301-330
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Journal article (peer-reviewed)abstract
- Interspecific hybridization in mammals causes hybrid dysgenesis effects, such as sterility and abnormal placentation. Here, we describe a novel obesity syndrome caused by interspecific hybridization in the genus Mus and show that this obesity, appearing sporadically in F1 littermates derived from inbred strains, has an epigenetic basis. Mus hybrids from various strains of M. musculus and M. spretus were generated and the sporadic obese phenotype was confirmed through assessment of physiological and biochemical parameters in littermates. To understand the underlying mechanisms, large-scale and candidate gene expression assays, global DNA methylation assays and allelic expression analysis were performed. Studies showed that obese hybrids are similar to other known models of obesity. While increased axial growth indicated a defect in POMC pathway, comparison of global gene expression patterns in brain of obese F1 and obese Pomc mutant mice showed little similarity. In F1 obese mice many genes involved in the maintenance of epigenetic states, as well as several imprinted genes, were differentially expressed. Global DNA methylation analysis in brain showed that increased methylation levels were associated with obesity. The imprinted gene Gnasxl, known to be important in lipid homeostasis, was found over expressed in the obese hybrids. Allelic expression and methylation analysis of Gnasxl showed that alterations of epigenetic marks underlying F1 obesity are probably many and multi-factorial. CONCLUSIONS: This model of obesity, which is both spontaneous and epigenetic, may be a useful tool to address the epigenetic aspects of clinical obesity.
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| 10. |
- Wedenberg, Mina, et al.
(author)
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Analytical description of the LET dependence of cell survival using the repairable-conditionally repairable damage model
- 2010
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In: Radiation Research. - 0033-7587 .- 1938-5404. ; 96, s. S534-S534
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Journal article (peer-reviewed)abstract
- In light-ion radiation therapy, both the dose and the local energy spectrum, which is often characterized with the linear energy transfer (LET), must be considered. In treatment optimization, it is advantageous to use a radiobiological model that analytically accounts for both dose and LET for the ion type of interest. With such a model the biological effect can also be estimated for dose and LET combinations for which there are no observations in the underlying experimental data. In this study, the repairable-conditionally repairable (RCR) damage model was extended by expressing its parameters as functions of LET to provide a radiobiological model that accounts for both the dose and the LET for a given ion type and cell line. This LET-parameterized RCR model was fitted to published cell survival data for HSG and V79 cells irradiated with carbon ions and for T1 cells irradiated with helium ions. To test the robustness of the model, fittings to only a subset of the data were performed. Good agreement with the cell survival data was obtained, including survival data for LET values not used for model fitting, opening up the possibility of using the model in treatment planning for light ions.
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