| 1. |
- Schoch, Conrad L., et al.
(författare)
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Finding needles in haystacks: linking scientific names, reference specimens and molecular data for Fungi
- 2014
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Ingår i: Database: The Journal of Biological Databases and Curation. - : Oxford University Press (OUP). - 1758-0463. ; 2014:bau061, s. 1-21
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Tidskriftsartikel (refereegranskat)abstract
- DNA phylogenetic comparisons have shown that morphology-based species recognition often underestimates fungal diversity. Therefore, the need for accurate DNA sequence data, tied to both correct taxonomic names and clearly annotated specimen data, has never been greater. Furthermore, the growing number of molecular ecology and microbiome projects using high-throughput sequencing require fast and effective methods for en masse species assignments. In this article, we focus on selecting and re-annotating a set of marker reference sequences that represent each currently accepted order of Fungi. The particular focus is on sequences from the internal transcribed spacer region in the nuclear ribosomal cistron, derived from type specimens and/or ex-type cultures. Re-annotated and verified sequences were deposited in a curated public database at the National Center for Biotechnology Information (NCBI), namely the RefSeq Targeted Loci (RTL) database, and will be visible during routine sequence similarity searches with NR_prefixed accession numbers. A set of standards and protocols is proposed to improve the data quality of new sequences, and we suggest how type and other reference sequences can be used to improve identification of Fungi.
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| 2. |
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| 3. |
- Harmat, V., et al.
(författare)
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Structure and catalysis of acylaminoacyl peptidase: Closed and open subunits of a dimer oligopeptidase
- 2011
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 286:3, s. 1987-1998
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Tidskriftsartikel (refereegranskat)abstract
- Acylaminoacyl peptidase from Aeropyrum pernix is a homodimer that belongs to the prolyl oligopeptidase family. The monomer subunit is composed of one hydrolase and one propeller domain. Previous crystal structure determinations revealed that the propeller domain obstructed the access of substrate to the active site of both subunits. Here we investigated the structure and the kinetics of two mutant enzymes in which the aspartic acid of the catalytic triad was changed to alanine or asparagine. Using different substrates, we have determined the pH dependence of specificity rate constants, the rate-limiting step of catalysis, and the binding of substrates and inhibitors. The catalysis considerably depended both on the kind of mutation and on the nature of the substrate. The results were interpreted in terms of alterations in the position of the catalytic histidine side chain as demonstrated with crystal structure determination of the native and two mutant structures (D524N and D524A). Unexpectedly, in the homodimeric structures, only one subunit displayed the closed form of the enzyme. The other subunit exhibited an open gate to the catalytic site, thus revealing the structural basis that controls the oligopeptidase activity. The open form of the native enzyme displayed the catalytic triad in a distorted, inactive state. The mutations affected the closed, active form of the enzyme, disrupting its catalytic triad. We concluded that the two forms are at equilibrium and the substrates bind by the conformational selection mechanism.
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| 4. |
- Reymer, Anna, 1983, et al.
(författare)
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Orientation of aromatic residues in amyloid cores: Structural insights into prion fiber diversity
- 2014
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 111:48, s. 17158-17163
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Tidskriftsartikel (refereegranskat)abstract
- Structural conversion of one given protein sequence into different amyloid states, resulting in distinct phenotypes, is one of the most intriguing phenomena of protein biology. Despite great efforts the structural origin of prion diversity remains elusive, mainly because amyloids are insoluble yet noncrystalline and therefore not easily amenable to traditional structural-biology methods. We investigate two different phenotypic prion strains, weak and strong, of yeast translation termination factor Sup35 with respect to angular orientation of tyrosines using polarized light spectroscopy. By applying a combination of alignment methods the degree of fiber orientation can be assessed, which allows a relatively accurate determination of the aromatic ring angles. Surprisingly, the strains show identical average orientations of the tyrosines, which are evenly spread through the amyloid core. Small variations between the two strains are related to the local environment of a fraction of tyrosines outside the core, potentially reflecting differences in fibril packing.
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| 5. |
- Czeiter, Endre, et al.
(författare)
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Brain Injury Biomarkers May Improve the Predictive Power of the IMPACT Outcome Calculator
- 2012
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Ingår i: Journal of Neurotrauma. - : Mary Ann Liebert. - 0897-7151 .- 1557-9042. ; 29:9, s. 1770-1778
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Tidskriftsartikel (refereegranskat)abstract
- Outcome prediction following severe traumatic brain injury (sTBI) is a widely investigated field of research. A major breakthrough is represented by the IMPACT prognostic calculator based on admission data of more than 8500 patients. A growing body of scientific evidence has shown that clinically meaningful biomarkers, including glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase-L1 (UCH-L1), and alpha II-spectrin breakdown product (SBDP145), could also contribute to outcome prediction. The present study was initiated to assess whether the addition of biomarkers to the IMPACT prognostic calculator could improve its predictive power. Forty-five sTBI patients (GCS score <= 8) from four different sites were investigated. We utilized the core model of the IMPACT calculator (age, GCS motor score, and reaction of pupils), and measured the level of GFAP, UCH-L1, and SBDP145 in serum and cerebrospinal fluid (CSF). The forecast and actual 6-month outcomes were compared by logistic regression analysis. The results of the core model itself, as well as serum values of GFAP and CSF levels of SBDP145, showed a significant correlation with the 6-month mortality using a univariate analysis. In the core model, the Nagelkerke R-2 value was 0.214. With multivariate analysis we were able to increase this predictive power with one additional biomarker (GFAP in CSF) to R-2 = 0.476, while the application of three biomarker levels (GFAP in CSF, GFAP in serum, and SBDP145 in CSF) increased the Nagelkerke R-2 to 0.700. Our preliminary results underline the importance of biomarkers in outcome prediction, and encourage further investigation to expand the predictive power of contemporary outcome calculators and prognostic models in TBI.
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| 6. |
- Daldorff, Lars K. S., et al.
(författare)
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Two-way coupling of a global Hall magnetohydrodynamics model with a local implicit particle-in-cell model
- 2014
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Ingår i: Journal of Computational Physics. - : Elsevier BV. - 0021-9991 .- 1090-2716. ; 268, s. 236-254
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Tidskriftsartikel (refereegranskat)abstract
- Computational models based on a fluid description of the plasma, such as magnetohydrodynamic (MHD) and extended magnetohydrodynamic (XMHD) codes are highly efficient, but they miss the kinetic effects due to the assumptions of small gyro radius, charge neutrality, and Maxwellian thermal velocity distribution. Kinetic codes can properly take into account the kinetic effects, but they are orders of magnitude more expensive than the fluid codes due to the increased degrees of freedom. If the fluid description is acceptable in a large fraction of the computational domain, it makes sense to confine the kinetic model to the regions where kinetic effects are important. This coupled approach can be much more efficient than a pure kinetic model. The speed up is approximately the volume ratio of the full domain relative to the kinetic regions assuming that the kinetic code uses a uniform grid. This idea has been advocated by [1] but their coupling was limited to one dimension and they employed drastically different grid resolutions in the fluid and kinetic models. We describe a fully two-dimensional two-way coupling of a Hall MHD model BATS-R-US with an implicit Particle-in-Cell (PIC) model iPIC3D. The coupling can be performed with identical grid resolutions and time steps. We call this coupled computational plasma model MHD-EPIC (MHD with Embedded PIC regions). Our verification tests show that MHD-EPIC works accurately and robustly. We show a two-dimensional magnetosphere simulation as an illustration of the potential future applications of MHD-EPIC.
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| 7. |
- Dehlin, S., et al.
(författare)
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Practical application of a newly developed automated building energy-analysis software module prototype
- 2012
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Ingår i: eWork and eBusiness in Architecture, Engineering and Construction. - Boca Raton : CRC Press, Taylor & Francis Group. - 9780415621281 ; , s. 45-49
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Konferensbidrag (refereegranskat)abstract
- One key challenge when it comes to developing industrial building concepts for the housing industry is improving the energy performance of buildings, while at the same time ensuring that the end product remains affordable and attractive to customers. This paper summarises the findings from the application of a newly developed prototype for an automated energy-analysis software module in a real-life project.The prototype is used for the energy analysis of the low-energy, multi-family residential P303 concept developed by NCC Construction Sverige AB - a leading construction and development company in the Nordic region. A building concept is based on continuity and repetitions of most of the building components. Most of its characteristics are known and defined beforehand and only a few parameters vary due to the adaptation of the concept, for example, the configuration or site location. In energy performance calculations, the proposed energy-analysis software module prototype processes the known parameters as constants and only varies the unknown parameters. The energy calculations are then carried out by the calculation kernel from the dynamic building simulation software module, VIP Energy, and the result is exported to an Excel spreadsheet where it is presented in a table. This makes it possible, in a practical manner, to execute a larger number of performance analyses in a shorter time, investigating different design alternatives and configurations and thereby facilitating optimisation towards the best possible design solution. The case study presented in this paper simulated energy losses through the building envelope of a real P303 building. The parameters that were varied are the location and orientation of the building and various energy characteristics of windows/glazing.
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| 8. |
- Iovino, Mariangela, et al.
(författare)
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The novel MAPT mutation K298E: mechanisms of mutant tau toxicity, brain pathology and tau expression in induced fibroblast-derived neurons
- 2014
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Ingår i: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 1432-0533 .- 0001-6322. ; 127:2, s. 283-295
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Tidskriftsartikel (refereegranskat)abstract
- Frontotemporal lobar degeneration (FTLD) consists of a group of neurodegenerative diseases characterized by behavioural and executive impairment, language disorders and motor dysfunction. About 20-30 % of cases are inherited in a dominant manner. Mutations in the microtubule-associated protein tau gene (MAPT) cause frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17T). Here we report a novel MAPT mutation (K298E) in exon 10 in a patient with FTDP-17T. Neuropathological studies of post-mortem brain showed widespread neuronal loss and gliosis and abundant deposition of hyperphosphorylated tau in neurons and glia. Molecular studies demonstrated that the K298E mutation affects both protein function and alternative mRNA splicing. Fibroblasts from a skin biopsy of the proband taken at post-mortem were directly induced into neurons (iNs) and expressed both 3-repeat and 4-repeat tau isoforms. As well as contributing new knowledge on MAPT mutations in FTDP-17T, this is the first example of the successful generation of iNs from skin cells retrieved post-mortem.
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| 9. |
- Jacobson, Therese, et al.
(författare)
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Arsenite interferes with protein folding and triggers formation of protein aggregates in yeast.
- 2012
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Ingår i: Journal of cell science. - : The Company of Biologists. - 1477-9137 .- 0021-9533. ; 125:21, s. 5073-83
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Tidskriftsartikel (refereegranskat)abstract
- Several metals and metalloids profoundly affect biological systems, but their impact on the proteome and mechanisms of toxicity are not fully understood. Here, we demonstrate that arsenite causes protein aggregation in Saccharomyces cerevisiae. Various molecular chaperones were found to be associated with arsenite-induced aggregates indicating that this metalloid promotes protein misfolding. Using in vivo and in vitro assays, we show that proteins in the process of synthesis/folding are particularly sensitive to arsenite-induced aggregation, that arsenite interferes with protein folding by acting on unfolded polypeptides, and that arsenite directly inhibits chaperone activity. Thus, folding inhibition contributes to arsenite toxicity in two ways: by aggregate formation and by chaperone inhibition. Importantly, arsenite-induced protein aggregates can act as seeds committing other, labile proteins to misfold and aggregate. Our findings describe a novel mechanism of toxicity that may explain the suggested role of this metalloid in the etiology and pathogenesis of protein folding disorders associated with arsenic poisoning.
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| 10. |
- Tamás, Markus J., 1970, et al.
(författare)
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Heavy Metals and Metalloids As a Cause for Protein Misfolding and Aggregation
- 2014
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Ingår i: Biomolecules. - : MDPI AG. - 2218-273X. ; 4:1, s. 252-267
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Tidskriftsartikel (refereegranskat)abstract
- While the toxicity of metals and metalloids, like arsenic, cadmium, mercury, lead and chromium, is undisputed, the underlying molecular mechanisms are not entirely clear. General consensus holds that proteins are the prime targets; heavy metals interfere with the physiological activity of specific, particularly susceptible proteins, either by forming a complex with functional side chain groups or by displacing essential metal ions in metalloproteins. Recent studies have revealed an additional mode of metal action targeted at proteins in a non-native state; certain heavy metals and metalloids have been found to inhibit the in vitro refolding of chemically denatured proteins, to interfere with protein folding in vivo and to cause aggregation of nascent proteins in living cells. Apparently, unfolded proteins with motile backbone and side chains are considerably more prone to engage in stable, pluridentate metal complexes than native proteins with their well-defined 3D structure. By interfering with the folding process, heavy metal ions and metalloids profoundly affect protein homeostasis and cell viability. This review describes how heavy metals impede protein folding and promote protein aggregation, how cells regulate quality control systems to protect themselves from metal toxicity and how metals might contribute to protein misfolding disorders.
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