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Search Results: 1 - 10 of 44918 matches for " Michael Thorsen "
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Mediator regulates non-coding RNA transcription at fission yeast centromeres
Michael Thorsen, Heidi Hansen, Michela Venturi, Steen Holmberg, Genevieve Thon
Epigenetics & Chromatin , 2012, DOI: 10.1186/1756-8935-5-19
Abstract: We found that the Med8-Med18-Med20 submodule of the Mediator complex is required for the transcriptional regulation of native centromeric dh and dg repeats and for the silencing of reporter genes inserted in centromeric heterochromatin. Mutations in the Med8-Med18-Med20 submodule did not alter Mediator occupancy at centromeres; however, they led to an increased recruitment of RNA polymerase II to centromeres and reduced levels of centromeric H3K9 methylation accounting for the centromeric desilencing. Further, we observed that Med18 and Med20 were required for efficient processing of dh transcripts into siRNA. Consistent with defects in centromeric heterochromatin, cells lacking Med18 or Med20 displayed elevated rates of mitotic chromosome loss.Our data demonstrate a role for the Med8-Med18-Med20 Mediator submodule in the regulation of non-coding RNA transcription at Schizosaccharomyces pombe centromeres. In wild-type cells this submodule limits RNA polymerase II access to the heterochromatic DNA of the centromeres. Additionally, the submodule may act as an assembly platform for the RNAi machinery or regulate the activity of the RNAi pathway. Consequently, Med8-Med18-Med20 is required for silencing of centromeres and proper mitotic chromosome segregation.Mediator is a large (approximately 1 MDa) protein complex that conveys regulatory signals to RNA polymerase II (Pol II). The Saccharomyces cerevisiae Mediator was the first to be characterized but Mediators have since then been described in many other species. A comparative genomics approach of approximately 70 eukaryotic genomes shows that although its exact subunit composition varies, Mediator is conserved across the eukaryotic kingdom [1]. The Schizosaccharomyces pombe Mediator consists of at least 20 subunits, all of which appear to have orthologues in Drosophila melanogaster, Caenorhabditis elegans and Homo sapiens[2].Three distinct domains (head, middle and tail) have been identified by electron microscopy on
Profiling of micrometer sized laser beams in restricted volumes
Yevhen Miroshnychenko,Otto Nielsen,Aske Thorsen,Michael Drewsen
Physics , 2012, DOI: 10.1364/AO.51.002341
Abstract: We present a method for determining the 3D intensity distribution of directed laser radiation with micrometer resolution in restricted volumes. Our method is based on in-coupling and guiding properties of optical fibers, with the current version requiring only few hundred micrometers. We characterize the performance of the method and experimentally demonstrate profiling of micrometer sized laser beams. We discuss the limiting factors and routes towards a further increase of the resolution and beam profiling in even more restricted volumes. Finally, as an application example, we present profiling of laser beams inside a micro ion trap with integrated optical fibers.
The paradoxes of gerotranscendence: The theory of gerotranscendence in a cultural gerontological and post-modernist perspective
Kirsten Thorsen
Norsk Epidemiologi , 2009,
Abstract: ABSTRACT This article presents a theoretical analysis and discussion of the theory of gerotranscendence, formulated by Lars Tornstam (University of Uppsala, Sweden). The theory is presented as a meta-theory of ageing, as a theory of universal and general ageing processes. Ageing is seen as an urge (a drive) towards a less engaged posititon in the wordly life, moving towards a higher degree of transcendence, with a more cosmic outlook and another definition of reality. In this article the theory is discussed from another theoretical position; Ageing seen in a cultural gerontological perspective, as a varied culturally and historically situated phenomenon – differing in different times and different cultures. The theoretical perspective underlines that ageing is complex dialectical processes, an intertwined interplay between individual development and cultural change. The varied individual ageing processes are not seen as the result of drives . In Western post-modern cultures the ageing processes are becoming manifold, often contradictory. Elderly present versions of the selves that are becoming complex, multiplied (multiple selves), acting at different scenes, stamped by varied cultural values, presenting mixed versions of activity and passivity, engagement and retractment, wordliness and transcendence. Key words: Ageing theories; gerotranscendence; cultural gerontology; postmodernism
MRN1 Implicates Chromatin Remodeling Complexes and Architectural Factors in mRNA Maturation
Louis Düring, Michael Thorsen, Darima Sophia Njama Petersen, Brian K?ster, Torben Heick Jensen, Steen Holmberg
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0044373
Abstract: A functional relationship between chromatin structure and mRNA processing events has been suggested, however, so far only a few involved factors have been characterized. Here we show that rsc nhp6ΔΔ mutants, deficient for the function of the chromatin remodeling factor RSC and the chromatin architectural proteins Nhp6A/Nhp6B, accumulate intron-containing pre-mRNA at the restrictive temperature. In addition, we demonstrate that rsc8-ts16 nhp6ΔΔ cells contain low levels of U6 snRNA and U4/U6 di-snRNA that is further exacerbated after two hours growth at the restrictive temperature. This change in U6 snRNA and U4/U6 di-snRNA levels in rsc8-ts16 nhp6ΔΔ cells is indicative of splicing deficient conditions. We identify MRN1 (multi-copy suppressor of rsc nhp6ΔΔ) as a growth suppressor of rsc nhp6ΔΔ synthetic sickness. Mrn1 is an RNA binding protein that localizes both to the nucleus and cytoplasm. Genetic interactions are observed between 2 μm-MRN1 and the splicing deficient mutants snt309Δ, prp3, prp4, and prp22, and additional genetic analyses link MRN1, SNT309, NHP6A/B, SWI/SNF, and RSC supporting the notion of a role of chromatin structure in mRNA processing.
Genetic basis of arsenite and cadmium tolerance in Saccharomyces cerevisiae
Michael Thorsen, Gabriel G Perrone, Erik Kristiansson, Mathew Traini, Tian Ye, Ian W Dawes, Olle Nerman, Markus J Tamás
BMC Genomics , 2009, DOI: 10.1186/1471-2164-10-105
Abstract: To gain insight into metal action and cellular tolerance mechanisms, we carried out genome-wide screening of the Saccharomyces cerevisiae haploid and homozygous diploid deletion mutant collections and scored for reduced growth in the presence of arsenite or cadmium. Processes found to be required for tolerance to both metals included sulphur and glutathione biosynthesis, environmental sensing, mRNA synthesis and transcription, and vacuolar/endosomal transport and sorting. We also identified metal-specific defence processes. Arsenite-specific defence functions were related to cell cycle regulation, lipid and fatty acid metabolism, mitochondrial biogenesis, and the cytoskeleton whereas cadmium-specific defence functions were mainly related to sugar/carbohydrate metabolism, and metal-ion homeostasis and transport. Molecular evidence indicated that the cytoskeleton is targeted by arsenite and that phosphorylation of the Snf1p kinase is required for cadmium tolerance.This study has pin-pointed core functions that protect cells from arsenite and cadmium toxicity. It also emphasizes the existence of both common and specific defence systems. Since many of the yeast genes that confer tolerance to these agents have homologues in humans, similar biological processes may act in yeast and humans to prevent metal toxicity and carcinogenesis.The presence of nonessential metals like arsenic (As) and cadmium (Cd) in the environment is prevalent. Since these metals are highly toxic, they pose a considerable threat to nature and to human health. The main routes of poisoning are through occupational exposure or through ingestion of contaminated food and water. Pollution of soils with toxic agents is a common global problem, and contamination of drinking water by arsenic is a major health concern because of the large number of contaminated sites and people at risk. These metals are implicated in a broad spectrum of degenerative conditions in humans, including neurotoxicity, nephrotoxici
Concerted Action of the Ubiquitin-Fusion Degradation Protein 1 (Ufd1) and Sumo-Targeted Ubiquitin Ligases (STUbLs) in the DNA-Damage Response
Julie Bonne K?hler, Maria Louise M?nster J?rgensen, Gabriele Beinoraité, Michael Thorsen, Geneviève Thon
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0080442
Abstract: In eukaryotes many players in the DNA-damage response (DDR) catalyze protein sumoylation or ubiquitylation. Emphasis has been placed on how these modifications orchestrate the sequential recruitment of repair factors to sites of DNA damage or stalled replication forks. Here, we shed light on a pathway in which sumoylated factors are eliminated through the coupled action of Sumo-targeted ubiquitin ligases (STUbLs) and the ubiquitin-fusion degradation protein 1 (Ufd1). Ufd1 is a subunit of the Cdc48-Ufd1-Npl4 complex implicated in the sorting of ubiquitylated substrates for degradation by the proteasome. We find that in fission yeast, Ufd1 interacts physically and functionally with the Sumo-targeted ubiquitin ligase (STUbL) Rfp1, homologous to human RNF4, and with the Sumo E3 ligase Pli1, homologous to human PIAS1. Deleting a C-terminal domain of Ufd1 that mediates the interaction of Ufd1 with Rfp1, Pli1, and Sumo (ufd1ΔCt213-342) lead to an accumulation of high-molecular-weight Sumo conjugates and caused severe genomic instabilities. The spectrum of sensitivity of ufd1ΔCt213-342 cells to genotoxins, the epistatic relationships of ufd1ΔCt213-342 with mutations in DNA repair factors, and the localization of the repair factor Rad22 in ufd1ΔCt213-342 cells point to ufd1ΔCt213-342 cells accumulating aberrant structures during replication that require homologous recombination (HR) for their repair. We present evidence that HR is however often not successful in ufd1ΔCt213-342 cells and we identify Rad22 as one of the high-molecular-weight conjugates accumulating in the ufd1ΔCt213-342 mutant consistent with Rad22 being a STUbL/Ufd1 substrate. Suggesting a direct role of Ufd1 in the processing of Sumo-conjugates, Ufd1 formed nuclear foci colocalizing with Sumo during the DDR, and Sumo-conjugates accumulated in foci in the ufd1ΔCt213-342 mutant. Broader functional relationships between Ufd1 and STUbLs conceivably affect numerous cellular processes beyond the DDR.
Livskvalitet for personer med demenssykdom – sett i et livsl psperspektiv - En narrativ tiln rming basert p p r rendes fortellinger
Signe Tretteteig,Kirsten Thorsen
Nordisk Tidsskrift for Helseforskning , 2012,
Abstract: Artikkelen bygger p en unders kelse om hva som oppleves som god livskvalitet for personer med demenssykdom under sykdomsforl pet, basert p kvalitative intervjuer med p r rende. Studien utvider livskvalitetsbegrepet ved anvende et livsl psperspektiv. Den viser hvordan personens livserfaringer p virker mulighetene til oppleve livskvalitet i omsorgsbolig gjennom sykdomsprosessen. N re familierelasjoner er s rlig betydningsfulle for livskvaliteten for personer med demenssykdom ved flytting til omsorgsbolig, for opplevelse av sammenheng i livet, selvbekreftelse og identitetsst tte. Betydningen av livskvalitetsaspekter forbundet med tidligere liv endrer seg etter hvert som demenssykdommen utvikler seg. I en sen fase av demenssykdommen ser det ut til at opplevelsen av livskvalitet i st rre grad enn f r handler om personalets og andre n re omsorgspersoners evne til gi trygghet og omsorg, og tidligere livskvalitetsaspekter trer i bakgrunnen. At personalet anvender livshistorisk kunnskap er sentralt for at beboerne skal f individuelt tilrettelagt livsinnhold, aktiviteter og omsorg som fremmer livskvalitet.
Impairments, mastery, and loneliness. A prospective study of loneliness among older adults
Magnhild Nicolaisen,Kirsten Thorsen
Norsk Epidemiologi , 2012,
Abstract: Old age is commonly associated with loneliness as loss of partner and friends, retirement, deteriorating health and functional impairments may make way for loneliness. An ageing population may give rise to concern for growing numbers of lonely people. The study explores loneliness among older people 67-79 years old (N=699), living in their own homes, examining whether and how socio-demographic factors, subjective health, and mastery influence loneliness among people with no impairments and people with impairments. The study uses cross-sectional and longitudinal (five-year panel) data from the Norwegian Life Course, Ageing and Generation study (NorLAG), calculating the risk of loneliness at T1, and prospectively at T2. Mastery is the only factor significantly influencing the risk of loneliness both at T1 and T2, both for older people with impairments and for those without impairments. A high level of mastery is related to a lower risk of loneliness. Being married or cohabitant are related to a lower risk of loneliness, among those without impairments both at T1 and at T2, among those with impairments only at T1. Age, gender and subjective health were not independently related to loneliness at any time. The results suggest that the subjective feeling of mastery is important to avoid loneliness, both at T1 and prospectively at T2 in both groups
A subgroup of plant aquaporins facilitate the bi-directional diffusion of As(OH)3 and Sb(OH)3 across membranes
Gerd P Bienert, Michael Thorsen, Manuela D Schüssler, Henrik R Nilsson, Annemarie Wagner, Markus J Tamás, Thomas P Jahn
BMC Biology , 2008, DOI: 10.1186/1741-7007-6-26
Abstract: Here we show that the Nodulin26-like Intrinsic Proteins (NIPs) AtNIP5;1 and AtNIP6;1 from Arabidopsis thaliana, OsNIP2;1 and OsNIP3;2 from Oryza sativa, and LjNIP5;1 and LjNIP6;1 from Lotus japonicus are bi-directional As(III) channels. Expression of these NIPs sensitized yeast cells to As(III) and antimonite (Sb(III)), and direct transport assays confirmed their ability to facilitate As(III) transport across cell membranes. On medium containing As(V), expression of the same NIPs improved yeast growth, probably due to increased As(III) efflux. Our data furthermore provide evidence that NIPs can discriminate between highly similar substrates and that they may have differential preferences in the direction of transport. A subgroup of As(III) permeable channels that group together in a phylogenetic tree required N-terminal truncation for functional expression in yeast.This is the first molecular identification of plant As(III) transport systems and we propose that metalloid transport through NIPs is a conserved and ancient feature. Our observations are potentially of great importance for improved remediation and tolerance of plants, and may provide a key to the development of low arsenic crops for food production.Arsenic is widespread in the Earth's crust and is highly available in the biosphere. Arsenic is acutely toxic to all organisms and is rated as a group I human carcinogen by the International Agency for Research of Cancer [1]. Due to its high bioavailability and toxicity, arsenic is considered a global health hazard. Contaminated drinking water is the main source of arsenic intake in several parts of the world. In Argentina, Australia, Bangladesh, Chile, China, Hungary, India, Mexico, Peru, Thailand, and the United States of America, arsenic concentrations higher than the permissible levels have been reported and negative effects on human health have been documented [2]. The second largest source of arsenic for humans is through ingestion of food that has accum
Functional Traits Reveal Processes Driving Natural Afforestation at Large Spatial Scales
Norman W. H. Mason, Susan K. Wiser, Sarah J. Richardson, Michael J. Thorsen, Robert J. Holdaway, Stéphane Dray, Fiona J. Thomson, Fiona E. Carswell
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0075219
Abstract: An understanding of the processes governing natural afforestation over large spatial scales is vital for enhancing forest carbon sequestration. Models of tree species occurrence probability in non-forest vegetation could potentially identify the primary variables determining natural afforestation. However, inferring processes governing afforestation using tree species occurrence is potentially problematic, since it is impossible to know whether observed occurrences are due to recruitment or persistence of existing trees following disturbance. Plant functional traits have the potential to reveal the processes by which key environmental and land cover variables influence afforestation. We used 10,061 survey plots to identify the primary environmental and land cover variables influencing tree occurrence probability in non-forest vegetation in New Zealand. We also examined how these variables influenced diversity of functional traits linked to plant ecological strategy and dispersal ability. Mean annual temperature was the most important environmental predictor of tree occurrence. Local woody cover and distance to forest were the most important land cover variables. Relationships between these variables and ecological strategy traits revealed a trade-off between ability to compete for light and colonize sites that were marginal for tree occurrence. Biotically dispersed species occurred less frequently with declining temperature and local woody cover, suggesting that abiotic stress limited their establishment and that biotic dispersal did not increase ability to colonize non-woody vegetation. Functional diversity for ecological strategy traits declined with declining temperature and woody cover and increasing distance to forest. Functional diversity for dispersal traits showed the opposite trend. This suggests that low temperatures and woody cover and high distance to forest may limit tree species establishment through filtering on ecological strategy traits, but not on dispersal traits. This study shows that ‘snapshot’ survey plot data, combined with functional trait data, may reveal the processes driving tree species establishment in non-forest vegetation over large spatial scales.
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