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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
Keratin23 (KRT23) Knockdown Decreases Proliferation and Affects the DNA Damage Response of Colon Cancer Cells
Karin Birkenkamp-Demtr?der, Stephan A. Hahn, Francisco Mansilla, Kasper Thorsen, Abdelouahid Maghnouj, Rikke Christensen, Bodil ?ster, Torben Falck ?rntoft
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0073593
Abstract: Keratin 23 (KRT23) is strongly expressed in colon adenocarcinomas but absent in normal colon mucosa. Array based methylation profiling of 40 colon samples showed that the promoter of KRT23 was methylated in normal colon mucosa, while hypomethylated in most adenocarcinomas. Promoter methylation correlated with absent expression, while increased KRT23 expression in tumor samples correlated with promoter hypomethylation, as confirmed by bisulfite sequencing. Demethylation induced KRT23 expression in vitro. Expression profiling of shRNA mediated stable KRT23 knockdown in colon cancer cell lines showed that KRT23 depletion affected molecules of the cell cycle and DNA replication, recombination and repair. In vitro analyses confirmed that KRT23 depletion significantly decreased the cellular proliferation of SW948 and LS1034 cells and markedly decreased the expression of genes involved in DNA damage response, mainly molecules of the double strand break repair homologous recombination pathway. KRT23 knockdown decreased the transcript and protein expression of key molecules as e.g. MRE11A, E2F1, RAD51 and BRCA1. Knockdown of KRT23 rendered colon cancer cells more sensitive to irradiation and reduced proliferation of the KRT23 depleted cells compared to irradiated control cells.
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
Discourses of positionality and the challenges of democratization in the global south: The case of Nepal and Cameroon
Jacob Thorsen,Teke J Ngomba
MedieKultur : Journal of Media and Communication Research , 2012,
Abstract: In this article, we argue that to conceptually and empirically grasp the dynamics and challenges of processes of civic participation, i.e., the deliberation and empowerment of disenfranchised and marginalized populations in the Global South, communication for social change scholars need to pay more attention to three issues: the quality of citizens’ self-perceptions in relation to their local milieu, inter-citizen perceptions and relations at the local level and lastly, the attendant consequences of these on citizens’ sense of efficacy. To grasp and comprehend the interplay of these three issues, we propose the adoption of Floya Anthias’ concept of narratives of location and positionality and demonstrate the heuristic vitality of this notion through a discussion of some local discourses of positionality in Nepal and Cameroon.
Tumor-specific usage of alternative transcription start sites in colorectal cancer identified by genome-wide exon array analysis
Kasper Thorsen, Troels Schepeler, Bodil ?ster, Mads H Rasmussen, S?ren Vang, Kai Wang, Kristian Q Hansen, Philippe Lamy, Jakob Pedersen, Asger Eller, Francisco Mansilla, Kirsti Laurila, Carsten Wiuf, S?ren Laurberg, Lars Dyrskj?t, Torben F ?rntoft, Claus L Andersen
BMC Genomics , 2011, DOI: 10.1186/1471-2164-12-505
Abstract: By profiling 108 colorectal samples using exon arrays, we identified nine genes (TCF12, OSBPL1A, TRAK1, ANK3, CHEK1, UGP2, LMO7, ACSL5, and SCIN) showing tumor-specific alternative TSS usage in both adenoma and cancer samples relative to normal mucosa. Analysis of independent exon array data sets corroborated these findings. Additionally, we confirmed the observed patterns for selected mRNAs using quantitative real-time reverse-transcription PCR. Interestingly, for some of the genes, the tumor-specific TSS usage was not restricted to colorectal cancer. A comprehensive survey of the nine genes in lung, bladder, liver, prostate, gastric, and brain cancer revealed significantly altered mRNA isoform ratios for CHEK1, OSBPL1A, and TCF12 in a subset of these cancer types.To identify the mechanism responsible for the shift in alternative TSS usage, we antagonized the Wnt-signaling pathway in DLD1 and Ls174T colorectal cancer cell lines, which remarkably led to a shift in the preferred TSS for both OSBPL1A and TRAK1. This indicated a regulatory role of the Wnt pathway in selecting TSS, possibly also involving TP53 and SOX9, as their transcription binding sites were enriched in the promoters of the tumor preferred isoforms together with their mRNA levels being increased in tumor samples.Finally, to evaluate the prognostic impact of the altered TSS usage, immunohistochemistry was used to show deregulation of the total protein levels of both TCF12 and OSBPL1A, corresponding to the mRNA levels observed. Furthermore, the level of nuclear TCF12 had a significant correlation to progression free survival in a cohort of 248 stage II colorectal cancer samples.Alternative TSS usage in colorectal adenoma and cancer samples has been shown for nine genes, and OSBPL1A and TRAK1 were found to be regulated in vitro by Wnt signaling. TCF12 protein expression was upregulated in cancer samples and correlated with progression free survival.Colorectal cancer (CRC) is a leading cause of cancer mo
Next-Generation Sequencing of RNA and DNA Isolated from Paired Fresh-Frozen and Formalin-Fixed Paraffin-Embedded Samples of Human Cancer and Normal Tissue
Jakob Hedegaard, Kasper Thorsen, Mette Katrine Lund, Anne-Mette K. Hein, Stephen Jacques Hamilton-Dutoit, S?ren Vang, Iver Nordentoft, Karin Birkenkamp-Demtr?der, Mogens Kruh?ffer, Henrik Hager, Bjarne Knudsen, Claus Lindbjerg Andersen, Karina Dalsgaard S?rensen, Jakob Skou Pedersen, Torben Falck ?rntoft, Lars Dyrskj?t
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0098187
Abstract: Formalin-fixed, paraffin-embedded (FFPE) tissues are an invaluable resource for clinical research. However, nucleic acids extracted from FFPE tissues are fragmented and chemically modified making them challenging to use in molecular studies. We analysed 23 fresh-frozen (FF), 35 FFPE and 38 paired FF/FFPE specimens, representing six different human tissue types (bladder, prostate and colon carcinoma; liver and colon normal tissue; reactive tonsil) in order to examine the potential use of FFPE samples in next-generation sequencing (NGS) based retrospective and prospective clinical studies. Two methods for DNA and three methods for RNA extraction from FFPE tissues were compared and were found to affect nucleic acid quantity and quality. DNA and RNA from selected FFPE and paired FF/FFPE specimens were used for exome and transcriptome analysis. Preparations of DNA Exome-Seq libraries was more challenging (29.5% success) than that of RNA-Seq libraries, presumably because of modifications to FFPE tissue-derived DNA. Libraries could still be prepared from RNA isolated from two-decade old FFPE tissues. Data were analysed using the CLC Bio Genomics Workbench and revealed systematic differences between FF and FFPE tissue-derived nucleic acid libraries. In spite of this, pairwise analysis of DNA Exome-Seq data showed concordance for 70–80% of variants in FF and FFPE samples stored for fewer than three years. RNA-Seq data showed high correlation of expression profiles in FF/FFPE pairs (Pearson Correlations of 0.90 +/- 0.05), irrespective of storage time (up to 244 months) and tissue type. A common set of 1,494 genes was identified with expression profiles that were significantly different between paired FF and FFPE samples irrespective of tissue type. Our results are promising and suggest that NGS can be used to study FFPE specimens in both prospective and retrospective archive-based studies in which FF specimens are not available.
Functional Screening Identifies miRNAs Influencing Apoptosis and Proliferation in Colorectal Cancer
Lise Lotte Christensen, Anja Holm, Juha Rantala, Olli Kallioniemi, Mads H. Rasmussen, Marie S. Ostenfeld, Frederik Dagnaes-Hansen, Bodil ?ster, Troels Schepeler, Heidi Tobiasen, Kasper Thorsen, Oliver M. Sieber, Peter Gibbs, Philippe Lamy, Torben F. Hansen, Anders Jakobsen, Eva M. Riising, Kristian Helin, Jan Lubinski, Rikke Hagemann-Madsen, S?ren Laurberg, Torben F. ?rntoft, Claus L. Andersen
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0096767
Abstract: MicroRNAs (miRNAs) play a critical role in many biological processes and are aberrantly expressed in human cancers. Particular miRNAs function either as tumor suppressors or oncogenes and appear to have diagnostic and prognostic significance. Although numerous miRNAs are dys-regulated in colorectal cancer (CRC) only a small fraction has been characterized functionally. Using high-throughput functional screening and miRNA profiling of clinical samples the present study aims at identifying miRNAs important for the control of cellular growth and/or apoptosis in CRC. The high-throughput functional screening was carried out in six CRC cell lines transfected with a pre-miR library including 319 synthetic human pre-miRs. Phenotypic alterations were evaluated by immunostaining of cleaved cPARP (apoptosis) or MKI67 (proliferation). Additionally, TaqMan Human MicroRNA Array Set v2.0 was used to profile the expression of 667 miRNAs in 14 normal colon mucosa and 46 microsatellite stable stage II CRC patients. Among the miRNAs that induced growth arrest and apoptosis in the CRC cell lines, and at same time were dys-regulated in the clinical samples, miR-375 was selected for further analysis. Independent in vitro analysis of transient and stable transfected CRC cell lines confirmed that miR-375 reduces cell viability through the induction of apoptotic death. We identified YAP1 as a direct miR-375 target in CRC and show that HELLS and NOLC1 are down-stream targets. Knock-down of YAP1 mimicked the phenotype induced by miR-375 over-expression indicating that miR-375 most likely exerts its pro-apoptotic role through YAP1 and its anti-apoptotic down-stream targets BIRC5 and BCL2L1. Finally, in vivo analysis of mouse xenograft tumors showed that miR-375 expression significantly reduced tumor growth. We conclude that the high-throughput screening successfully identified miRNAs that induce apoptosis and/or inhibit proliferation in CRC cells. Finally, combining the functional screening with profiling of CRC tissue samples we identified clinically relevant miRNAs and miRNA targets in CRC.
Location of DNA damage by charge exchanging repair enzymes: effects of cooperativity on location time
Kasper Eriksen
Theoretical Biology and Medical Modelling , 2005, DOI: 10.1186/1742-4682-2-15
Abstract: Here the size of the speed-up gained from this charge exchange mechanism is calculated and the characteristic length and time scales are identified. In particular, for Escherichia coli, I estimate the speed-up is 50000/N, where N is the number of repair enzymes participating in the charge exchange mechanism. Even though N is not exactly known, a speed-up of order 10 is not entirely unreasonable. Furthermore, upon over expression of all the repair enzymes, the location time only varies as N-1/2 and not as 1/N.The revolutionary hypothesis that DNA repair enzymes use charge exchange along DNA to locate damaged sites more efficiently is actually sound from a purely theoretical point of view. Furthermore, the predicted collective behavior of the location time is important in assessing the impact of stress-ful and radioactive environments on individual cell mutation rates.Bases in DNA suffer damage both from normal cellular functions such as metabolism and from external oxidative stress and radiation. Naturally the cell has several lines of defense against direct lesions and ensuing mutagenic mispairings [1-3]. Oxidation of the base guanine (G) often results in the formation of 8-oxo-G (7,8-dihydro-8-oxo-2'-deoxyguanosine) [4]. During replication, 8-oxo-G can pair both with cytosine (C) and adenine (A) [5]. Following another round of replication, the 8-oxo-G:A pairs give rise to G:C to T:A mutations (if not corrected). In Escherichia coli, 8-oxo-G:C pairs are detected by the DNA glycosylase MutM (formamidopyrimidine glycosylase), which subsequently excises the 8-oxo-G from the DNA leaving an abasic site where the strand is nicked at both the 3' and 5' ends [6]. The abasic site is further processed by the base excision pathway (BER), eventually leading to the insertion of a G opposite the remaining C. The action of MutM brings the number of adenines A misincorporated opposite 8-oxo-G during replication down to around one per one million bases, even in cells challenged by H
Introducing Cadabra: a symbolic computer algebra system for field theory problems
Peeters, Kasper
High Energy Physics - Phenomenology , 2007,
Abstract: Cadabra is a new computer algebra system designed specifically for the solution of problems encountered in field theory. It has extensive functionality for tensor polynomial simplification taking care of Bianchi and Schouten identities, for fermions and anti-commuting variables, Clifford algebras and Fierz transformations, implicit coordinate dependence, multiple index types and many other field theory related concepts. The input format is a subset of TeX and thus easy to learn. Both a command-line and a graphical interface are available. The present paper is an introduction to the program using several concrete problems from gravity, supergravity and quantum field theory.
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