| 1. |
- Reinthaler, Eva M., et al.
(författare)
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TPP2 mutation associated with sterile brain inflammation mimicking MS
- 2018
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Ingår i: NEUROLOGY-GENETICS. - 2376-7839. ; 4:6
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Tidskriftsartikel (refereegranskat)abstract
- Objective To ascertain the genetic cause of a consanguineous family from Syria suffering from a sterile brain inflammation mimicking a mild nonprogressive form of MS.Methods We used homozygosity mapping and next-generation sequencing to detect the disease-causing gene in the affected siblings. In addition, we performed RNA and protein expression studies, enzymatic activity assays, immunohistochemistry, and targeted sequencing of further MS cases from Austria, Germany, Canada and Jordan.Results In this study, we describe the identification of a homozygous missense mutation (c.82T>G, p.Cys28Gly) in the tripeptidyl peptidase II (TPP2) gene in all 3 affected siblings of the family. Sequencing of all TPP2-coding exons in 826 MS cases identified one further homozygous missense variant (c.2027C>T, p.Thr676Ile) in a Jordanian MS patient. TPP2 protein expression in whole blood was reduced in the affected siblings. In contrast, TPP2 protein expression in postmortem brain tissue from MS patients without TPP2 mutations was highly upregulated.Conclusions The homozygous TPP2 mutation (p.Cys28Gly) is likely responsible for the inflammation phenotype in this family. TPP2 is an ubiquitously expressed serine peptidase that removes tripeptides from the N-terminal end of longer peptides. TPP2 is involved in various biological processes including the destruction of major histocompatibility complex Class I epitopes. Recessive loss-of-function mutations in TPP2 were described in patients with Evans syndrome, a rare autoimmune disease affecting the hematopoietic system. Based on the gene expression results in our MS autopsy brain samples, we further suggest that TPP2 may play a broader role in the inflammatory process in MS.
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| 2. |
- Lang, Daniel, et al.
(författare)
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The Physcomitrella patens chromosome-scale assembly reveals moss genome structure and evolution
- 2018
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Ingår i: The Plant Journal. - : Wiley. - 0960-7412 .- 1365-313X. ; 93:3, s. 515-533
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Tidskriftsartikel (refereegranskat)abstract
- The draft genome of the moss model, Physcomitrella patens, comprised approximately 2000 unordered scaffolds. In order to enable analyses of genome structure and evolution we generated a chromosome-scale genome assembly using genetic linkage as well as (end) sequencing of long DNA fragments. We find that 57% of the genome comprises transposable elements (TEs), some of which may be actively transposing during the life cycle. Unlike in flowering plant genomes, gene-and TE-rich regions show an overall even distribution along the chromosomes. However, the chromosomes are mono-centric with peaks of a class of Copia elements potentially coinciding with centromeres. Gene body methylation is evident in 5.7% of the protein-coding genes, typically coinciding with low GC and low expression. Some giant virus insertions are transcriptionally active and might protect gametes from viral infection via siRNA mediated silencing. Structure-based detection methods show that the genome evolved via two rounds of whole genome duplications (WGDs), apparently common in mosses but not in liverworts and hornworts. Several hundred genes are present in colinear regions conserved since the last common ancestor of plants. These syntenic regions are enriched for functions related to plant-specific cell growth and tissue organization. The P. patens genome lacks the TE-rich pericentromeric and gene-rich distal regions typical for most flowering plant genomes. More non-seed plant genomes are needed to unravel how plant genomes evolve, and to understand whether the P. patens genome structure is typical for mosses or bryophytes.
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| 3. |
- Stockem, Irina, et al.
(författare)
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Anomalous Phonon Lifetime Shortening in Paramagnetic CrN Caused by Spin-Lattice Coupling: A Combined Spin and Ab Initio Molecular Dynamics Study
- 2018
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Ingår i: Physical Review Letters. - : AMER PHYSICAL SOC. - 0031-9007 .- 1079-7114. ; 121:12
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Tidskriftsartikel (refereegranskat)abstract
- We study the mutual coupling of spin fluctuations and lattice vibrations in paramagnetic CrN by combining atomistic spin dynamics and ab initio molecular dynamics. The two degrees of freedom are dynamically coupled, leading to nonadiabatic effects. Those effects suppress the phonon lifetimes at low temperature compared to an adiabatic approach. The dynamic coupling identified here provides an explanation for the experimentally observed unexpected temperature dependence of the thermal conductivity of magnetic semiconductors above the magnetic ordering temperature.
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| 4. |
- Zhang, Xi, et al.
(författare)
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Temperature dependence of the stacking-fault Gibbs energy for Al, Cu, and Ni
- 2018
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Ingår i: Physical Review B. Condensed Matter and Materials Physics. - : American Physical Society (APS). - 1098-0121 .- 1550-235X. ; 98:22
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Tidskriftsartikel (refereegranskat)abstract
- The temperature-dependent intrinsic stacking fault Gibbs energy is computed based on highly converged density-functional-theory (DFT) calculations for the three prototype face-centered cubic metals Al, Cu, and Ni. All relevant temperature-dependent contributions are considered including electronic, vibrational, magnetic, and explicit anharmonic Gibbs energy contributions as well as coupling terms employing state-of-the-art statistical sampling techniques. Particular emphasis is put on a careful comparison of different theoretical concepts to derive the stacking fault energy such as the axial-next-nearest-neighbor-Ising (ANNNI) model or the vacuum-slab approach. Our theoretical results are compared with an extensive set of previous theoretical and experimental data. Large uncertainties in the experimental data highlight the necessity of complementary parameter-free calculations. Specifically, the temperature dependence is experimentally unknown and poorly described by thermodynamic databases. Whereas CALPHAD derived data shows an increase of the stacking fault energy with temperature for two of the systems (Cu and Ni), our results predict a decrease for all studied systems. For Ni, the temperature induced change is in fact so strong that in the temperature interval relevant for super-alloy applications the stacking fault energy falls below one third of the low temperature value. Such large changes clearly call for a revision of the stacking fault energy when modeling or designing alloys based on such elements.
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