| 1. |
- Gu, Gucci Jijuan, 1984-, et al.
(författare)
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Elevated MARK2-Dependent Phosphorylation of Tau in Alzheimer's Disease
- 2013
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Ingår i: Journal of Alzheimer's Disease. - 1387-2877 .- 1875-8908. ; 33:3, s. 699-713
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Tidskriftsartikel (refereegranskat)abstract
- The appearance of neurofibrillary tangles (NFT), one of the major hallmarks of Alzheimer's disease (AD), is most likely caused by inappropriate phosphorylation and/or dephosphorylation of tau, eventually leading to the accumulation of NFTs. Enhanced phosphorylation of tau on Ser(262) is detected early in the course of the disease and may have a role in the formation of tangles. Several kinases such as microtubule-affinity regulating kinase (MARK), protein kinase A, calcium calmodulin kinase II, and checkpoint kinase 2 are known to phosphorylate tau on Ser(262) in vitro. In this study, we took advantage of the in situ proximity ligation assay to investigate the role of MARK2, one of the four MARK isoforms, in AD. We demonstrate that MARK2 interacts with tau and phosphorylates tau at Ser(262) in stably transfected NIH/3T3 cells expressing human recombinant tau. Staurosporine, a protein kinase inhibitor, significantly reduced the interaction between MARK2 and tau, and also phosphorylation of tau at Ser(262). Furthermore, we observed elevated interactions between MARK2 and tau in post-mortem human AD brains, compared to samples from non-demented elderly controls. Our results from transfected cells demonstrate a specific interaction between MARK2 and tau, as well as MARK2-dependent phosphorylation of tau at Ser(262). Furthermore, the elevated interactions between MARK2 and tau in AD brain sections suggests that MARK2 may play an important role in early phosphorylation of tau in AD, possibly qualifying as a therapeutic target for intervention to prevent disease progression.
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| 2. |
- Amin, Kawa, 1963-
(författare)
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Phytochemical analysis and hepatoprotective activity of Raphanus sativus var. Sativus in Sprague-Dawley rats : hepatoprotective activity of Raphanus sativus var
- 2020
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Ingår i: Phytochemical analysis and hepatoprotective activity of Raphanus sativus var. Sativus in Sprague-Dawley rats. - Benin City, Nigeria : African Journals Online (AJOL). - 1596-5996 .- 1596-9827. ; 19:8, s. 1745-1752
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- Purpose: To determine the phenolic and flavonoid contents of R. sativus rhizome ethanol extract and the hepatoprotective effect of the extract in rats.Methods: Folin–Ciocalteau and aluminum chloride colorimetric tests were used to determine the contents of phenols and flavonoids in the R. sativus extract. Male Sprague-Dawley rats induced with CCl4 to develop hepatotoxicity were treated orally with R. sativus extract for 4 weeks. The antioxidant and anti-inflammatory effects of the extract on the liver were determined by evaluating the concentration of oxidative analytes, serum liver enzymes, and lipids, and hepatic histopathology and cytochrome P450 2E1 expression.Results: R. sativus extract significantly (p < 0.05) reduced the hepatotoxic effect of CCl4 via its antioxidant activities and protection of liver tissues from oxidative damage.Conclusion: The hepatoprotective effects of R. sativus rhizome ethanol extract are attributed to its high phenolic and flavonoid contents.
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| 3. |
- Granmo, Tobias, 1972, et al.
(författare)
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Seminarieserien "Sinnenas musik"- känsliga bitar
- 2017
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Ingår i: Jonsereds Herrgård 18 oktober 2017.
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Konstnärligt arbete (övrigt vetenskapligt/konstnärligt)abstract
- SÖK! LYSSNA! ÖVERRASKA! Den uppmaningen ger tonsättaren Torbjörn Grass musikerna i sitt partitur Spektra för instrument och elektronik. Vid det fjärde Jonseredsseminariet i serien Sinnenas musik är det mot känseln uppmärksamheten riktas. Hur känsliga är vi för ljud och varför är vi så känsliga i fråga om vilken musik vi lyssnar på? Duo/Granmo Berg utforskar begreppet känsel ur ett musikaliskt perspektiv tillsammans med Ylva Öhrner är barnneurolog och överläkare vid Landstinget, Västmanland och Torbjörn Grass gitarrist och tonsättare med en stor passion för ljud. De samtalar och diskuterar vidare med en inbjuden skara specialister från olika områden.
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| 4. |
- Granmo, Tobias, 1972, et al.
(författare)
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Sinnenas musik " Öronmärkta toner"
- 2016
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Ingår i: Jonsereds Herrgård 13 September 2016.
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Konstnärligt arbete (övrigt vetenskapligt/konstnärligt)abstract
- År 1952 skakade tonsättaren John Cage om den klassiska musikscenen när han komponerade 4,32. Verket, i tre satser innehöll endast paus... Vid det andra Jonseredsseminariet i serien Sinnenas musik är det hörseln som kommer att stå i centrum för diskussionen. Hur lyssnar vi på musik och vad är musik? Hur påverkas vi av den musik vi hör? Vad kan vi med våra sinnens hjälp lära oss? Duo Granmo/Berg utforskar våra öron ur ett musikaliskt perspektivet tillsammans med Överläkare Radi Jönsson samt diskuterar och samtalar med en inbjuden skara av specialister från olika områden.
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| 5. |
- Massoumi, Ramin, et al.
(författare)
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The inflammatory mediator leukotriene D4 triggers a rapid reorganisation of the actin cytoskeleton in human intestinal epithelial cells
- 1998
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Ingår i: European Journal of Cell Biology. - 0171-9335. ; 76:3, s. 185-191
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Tidskriftsartikel (refereegranskat)abstract
- Epithelial cells play an important role in maintaining the intestinal mucosa barrier, a barrier that is impaired in several inflammatory conditions. The mechanisms behind this impairment are not known, but it can be presumed that structural alterations of the epithelial cells are involved. In support of this notion, we here show the inflammatory mediator leukotriene D4 (LTD4) triggered first a rapid (1Os) increase and immediately thereafter (30s) a sustained decrease in the cellular filamentous actin (F-actin) level in intestinal epithelial cells. The initial LTD4-induced increase in F-actin content was effectively blocked by preincubating the cells with either pertussis toxin or the tyrosine kinase inhibitor genistein. A possible involvement of the tyrosine kinase-dependent phosphatidylinositol-3-kinase (PI-3-kinase) in the polymerisation of actin was supported by the observations that LTD4 induced a translocation to a membrane fraction of PI-3-kinase and by the findings that wortmannin, a PI-3-kinase inhibitor, totally abolished both this translocation of PI-3-kinase as well as the initial LTD4-induced polymerisation of actin. In addition, pertussis toxin and genistein, both known to interfere with the LTD4-induced calcium signal, completely or partially reversed the actin-depolymerising effect of LTD4. The calcium ionophore ionomycin (30s) induced actin depolymerisation to the same extent as LTD4 (30s) did, but lacked the initial effect on actin polymerisation. In cells loaded with the calcium chelator MAPT, LTD4 induced a normal actin polymerisation response but the subsequent depolymerisation was completely inhibited. Similar results were obtained when the cells were preincubated with the protein kinase A inhibitor Rp-cAMPS, which has been shown to impair the LTD4-induced calcium signal in these epithelial cells. The present results show that the inflammatory mediator LTD4 triggers a reorganisation of the actin network in intestinal epithelial cells that is likely to contribute to the impairment of the intestinal barrier function.
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| 6. |
- Vaid, Roshan, 1987-
(författare)
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Transcription regulation across levels of chromatin organization
- 2020
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Konstnärligt arbete (övrigt vetenskapligt/konstnärligt)abstract
- With advancements in high-throughput sequencing and high-resolution microscopy techniques, the significance of genome organization in transcription regulation is rapidly unveiling. Nonetheless, we are yet far from completely understanding this key relationship. In this thesis, I utilize some of the cutting-edge high-throughput sequencing techniques along with the power of Drosophila as a model to understand some of the molecular mechanisms active at various levels of chromatin organization that influence gene expression. At the level of DNA sequence, our analysis revealed occupancy of CBP/p300, a transcription co-activator and histone acetyltransferase at insulator regions genome wide, we also identified a novel role of CBP as a barrier to heterochromatin spreading at these insulator regions.To gain insight into transcription regulation at level of nucleosomes, we perturbed histone modifications either chemically, by inhibiting histone deacetylases (HDACs), or genetically, by creating Drosophila mutants for the H3K14 residue. We found that the immediate transcriptional response to HDAC inhibition is only up-regulation (96 genes). Moreover, our results suggest that histone acetylation stimulates transcription by releasing promoter-proximal paused Pol II into elongation. In another study we discovered that acetylation of histone 3 lysine 14, H3K14ac, decorates some genes that lack canonical histone marks, thereby constituting a unique chromatin state. Further, Drosophila mutants expressing only H3K14R histones revealed that this residue is vital for expression of these genes, for animal survival and for developmental patterning.To further understand gene regulation during tissue specification in early embryo development, we utilized dorsoventral (DV) patterning as a model along with PRO-seq, ATAC-seq and ChIP-seq. We identified zygotically transcribed DV patterning genes that are spatially and temporally resolved. Most interestingly, the DV patterning genes are all highly paused and promoter proximal paused Pol II is released into active elongation in a tissue-specific manner. Finally our single cell RNA-seq (scRNA-seq) and HiC data in DV mutants revealed that differential regulation of gene expression occurs independently of differences in higher-order chromatin organization.Collectively, we provide evidence that transcription is being modulated at various levels of chromatin organization and our results suggest that histone modifications but not higher order chromatin organization influence transcriptional output.
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