| 1. |
- Pan, Gang, et al.
(author)
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PATZ1 down-regulates FADS1 by binding to rs174557 and is opposed by SP1/SREBP1c
- 2017
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In: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 45:5, s. 2408-2422
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Journal article (peer-reviewed)abstract
- The FADS1 and FADS2 genes in the FADS cluster encode the rate-limiting enzymes in the synthesis of long-chain polyunsaturated fatty acids (LC-PUFAs). Genetic variation in this region has been associated with a large number of diseases and traits many of them correlated to differences in metabolism of PUFAs. However, the causative variants leading to these associations have not been identified. Here we find that the multiallelic rs174557 located in an AluYe5 element in intron 1 of FADS1 is functional and lies within a PATZ1 binding site. The derived allele of rs174557, which is the common variant in most populations, diminishes binding of PATZ1, a transcription factor conferring allele-specific downregulation of FADS1 The PATZ1 binding site overlaps with a SP1 site. The competitive binding between the suppressive PATZ1 and the activating complex of SP1 and SREBP1c determines the enhancer activity of this region, which regulates expression of FADS1.
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| 2. |
- Farouq, Shiraz, 1980-, et al.
(author)
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Large-scale monitoring of operationally diverse district heating substations : A reference-group based approach
- 2020
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In: Engineering applications of artificial intelligence. - Oxford : Elsevier. - 0952-1976 .- 1873-6769. ; 90
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Journal article (peer-reviewed)abstract
- A typical district heating (DH) network consists of hundreds, sometimes thousands, of substations. In the absence of a well-understood prior model or data labels about each substation, the overall monitoring of such large number of substations can be challenging. To overcome the challenge, an approach based on the collective operational monitoring of each substation by a local group (i.e., the reference-group) of other similar substations in the network was formulated. Herein, if a substation of interest (i.e., the target) starts to behave differently in comparison to those in its reference-group, then it was designated as an outlier. The approach was demonstrated on the monitoring of the return temperature variable for atypical and faulty operational behavior in 778 substations associated with multi-dwelling buildings. The choice of an appropriate similarity measure along with its size k were the two important factors that enables a reference-group to effectively detect an outlier target. Thus, different similarity measures and size k for the construction of the reference-groups were investigated, which led to the selection of the Euclidean distance with k = 80. This setup resulted in the detection of 77 target substations that were outliers, i.e., the behavior of their return temperature changed in comparison to the majority of those in their respective reference-groups. Of these, 44 were detected due to the local construction of the reference-groups. In addition, six frequent patterns of deviating behavior in the return temperature of the substations were identified using the reference-group based approach, which were then further corroborated by the feedback from a DH domain expert. © 2020 Elsevier Ltd
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| 3. |
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| 4. |
- Nord, Stefan, 1980-
(author)
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The importance of maturation factors in 30S ribosomal subunit assembly
- 2010
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Doctoral thesis (other academic/artistic)abstract
- The assembly of the ribosome is a complex process that needs to be highly efficient to support maximum growth. Although the individual subunits of the ribosome can be reconstituted in vitro, such a reaction is inefficient in comparison to the assembly rate in vivo. What differentiates the in vivo from the in vitro assembly is primarily the presence of ribosome assembly proteins. These are proteins that assist in the assembly of the ribosomal subunits but are not part of the mature ribosome. In bacteria, the ribosome assembly proteins include rRNA processing enzymes and rRNA/ribosomal protein (r-protein) modifying enzymes. One set of ribosome assembly proteins, the ribosome maturation factors, have been difficult to classify due to their differences in structure and their apparent lack of similarities with regard to function. As part of this thesis, the previously uncharacterized RimP (ribosome maturation) protein formerly known as P15A or YhbC, was studied. Deletion of the rimP gene affected the growth rate more severely at 44°C than at 37°C and 30°C. Polysome profile analysis revealed a decrease in the amount of translating ribosomes and a corresponding increase in the amount of free 50S and 30S ribosomal subunits. The disproportionate large increase in 50S relative to 30S subunits indicated a 30S assembly defect. RimP was shown to localize to the 30S ribosomal subunit, and an accumulation of 17S rRNA, a precursor to 16S rRNA, supports a role for RimP in 30S subunit maturation. The results from in vitro reconstitution experiments have given valuable insights in the assembly of the 30S subunit. By using a recently developed method, the role of ribosome maturation factors Era, RimM and RimP during in vitro reconstitutions of the 30S subunit was investigated. Era was found to increase the incorporation rate for most of the late binding r-proteins, while RimM and RimP had more specific effects. RimM increased the incorporation rate for r-proteins S19 and S9 and inhibited the incorporation of S13 and S12, whereas RimP increased the incorporation rate primarily for S12 and S5. A comparison of the ribosome maturation factors RimP and RbfA (ribosome binding factor A) revealed structural similarities between the N-terminal domain of RimP and the single domain of RbfA. RbfA is a 15 kDa protein that was found to high copy-suppress a dominant C23U 16S rRNA mutation giving rise to cold-sensitivity in E. coli. A number of chromosomal suppressor mutations that increased the growth rate of an rbfA null mutant were isolated. The five strongest suppressor mutations were localized to the rpsE gene, for r-protein S5 and resulted in amino acid substitutions in three positions: G87A, G87S, G91A, A127V and A127T. These alterations improved translation and the processing of 16S rRNA in the rbfA null mutant. Moreover, they also suppressed the slow growth of the C23U rRNA mutant at 30, 37 and 44°C.
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| 5. |
- Nord, Stefan, 1980-, et al.
(author)
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The RimP protein is important for maturation of the 30S ribosomal subunit
- 2009
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In: Journal of Molecular Biology. - : Elsevier BV. - 0022-2836 .- 1089-8638. ; 386:3, s. 742-753
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Journal article (peer-reviewed)abstract
- The in vivo assembly of ribosomal subunits requires assistance by auxiliary proteins that are not part of mature ribosomes. More such assembly proteins have been identified for the assembly of the 50S than for the 30S ribosomal subunit. Here, we show that the RimP protein (formerly YhbC or P15a) is important for the maturation of the 30S subunit. A rimP deletion (DeltarimP135) mutant in Escherichia coli showed a temperature-sensitive growth phenotype as demonstrated by a 1.2-, 1.5-, and 2.5-fold lower growth rate at 30, 37, and 44 degrees C, respectively, compared to a wild-type strain. The mutant had a reduced amount of 70S ribosomes engaged in translation and showed a corresponding increase in the amount of free ribosomal subunits. In addition, the mutant showed a lower ratio of free 30S to 50S subunits as well as an accumulation of immature 16S rRNA compared to a wild-type strain, indicating a deficiency in the maturation of the 30S subunit. All of these effects were more pronounced at higher temperatures. RimP was found to be associated with free 30S subunits but not with free 50S subunits or with 70S ribosomes. The slow growth of the rimP deletion mutant was not suppressed by increased expression of any other known 30S maturation factor.
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| 6. |
- Persson, B. David, et al.
(author)
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BAF45b is required for efficient zika virus infection of HAP1 cells
- 2021
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In: Viruses. - : MDPI. - 1999-4915. ; 13:10
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Journal article (peer-reviewed)abstract
- The 2016 Zika virus (ZIKV) epidemic illustrates the impact of flaviviruses as emerging human pathogens. For unknown reasons, ZIKV replicates more efficiently in neural progenitor cells (NPCs) than in postmitotic neurons. Here, we identified host factors used by ZIKV using the NCI-60 library of cell lines and COMPARE analysis, and cross-analyzed this library with two other libraries of host factors with importance for ZIKV infection. We identified BAF45b, a subunit of the BAF (Brg1/Brm-associated factors) protein complexes that regulate differentiation of NPCs to post-mitotic neurons. ZIKV (and other flaviviruses) infected HAP1 cells deficient in expression of BAF45b and other BAF subunits less efficiently than wildtype (WT) HAP1 cells. We concluded that subunits of the BAF complex are important for infection of ZIKV and other flavivirus. Given their function in cell and tissue differentiation, such regulators may be important determinants of tropism and pathogenesis of arthropod-borne flaviviruses.
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