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Search Results: 1 - 10 of 211350 matches for " Claus L. Andersen "
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Clusterin expression can be modulated by changes in TCF1-mediated Wnt signaling
Troels Schepeler, Francisco Mansilla, Lise L Christensen, Torben F ?rntoft, Claus L Andersen
Journal of Molecular Signaling , 2007, DOI: 10.1186/1750-2187-2-6
Abstract: Over-expression of the cytoplasmic domain of E-cadherin tagged with GFP was used to abrogate Wnt signaling activity in LS174T and HCT116 colon carcinoma cells. This fusion construct sequestered signaling competent β-catenin whereby Wnt signaling was abrogated, and consequently cytoplasmic CLU protein levels increased as demonstrated by immunofluorescence. To determine which branch of the Wnt pathway was mediating the CLU response, we over-expressed dominant negative (dn) TCF1 and TCF4 transcription factors in stably transfected LS174T cells. We observed both intra- and extracellular levels of CLU protein to be induced by dnTCF1 but not dnTCF4. Subsequent analysis of the expression levels of three CLU mRNA variants by real time RT-PCR revealed only one CLU mRNA variant to be responsive to dnTCF1 over-expression. 5'-end RACE indicated that this CLU mRNA variant was shorter at the 5'-end than previously reported, and accordingly the translated protein was predicted to be shorter at the N-terminus and destined to the secretory pathway which fit our observations. Examination of the immediate expression kinetics of CLU after dnTCF1 over-expression using real time RT-PCR indicated that CLU might be a secondary Wnt target.In conclusion, we have demonstrated that the Wnt signaling pathway specifically regulates one out of three CLU mRNA variants via TCF1. This CLU transcript is shorter at the 5' end than reported by the RefSeq database, and produces the intracellular 60 kDa CLU protein isoform which is secreted as a ~80 kDa protein after post-translational processing.The clusterin (CLU) protein was first discovered more than 25 years ago in rat testis fluid because of its ability to facilitate clustering of a variety of cell types in culture[1]. Since then, homologues of the broadly expressed CLU gene have been identified in several species and CLU proteins have been found in most mammalian body fluids[2]. CLU is an enigmatic molecule, implicated in diverse biological proces
A Hidden Markov Model to estimate population mixture and allelic copy-numbers in cancers using Affymetrix SNP arrays
Philippe Lamy, Claus L Andersen, Lars Dyrskjot, Niels Torring, Carsten Wiuf
BMC Bioinformatics , 2007, DOI: 10.1186/1471-2105-8-434
Abstract: We show that our method is able to recover the underlying copy-number changes in simulated data sets with high accuracy (above 97.71%). Moreover, although the known copy-numbers could be well recovered in simulated cancer samples with more than 70% cancer cells (and less than 30% normal cells), we demonstrate that including the mixture proportion in the HMM increases the accuracy of the method. Finally, the method is tested on HapMap samples and on bladder and prostate cancer samples.The HMM method developed here uses the genotype calls of germline DNA and the allelic SNP intensities from the tumour DNA to estimate allelic copy-numbers (including changes) in the tumour. It differentiates between different events like uniparental disomy and allelic imbalances. Moreover, the HMM can estimate the mixture proportion, and thus inform about the purity of the tumour sample.Chromosomal abnormalities such as loss-of-heterozygosity (LOH) or genomic copy-number changes are frequent in tumour cells. LOH occurs when a heterozygous marker in germline DNA of an individual becomes homozygous in cancer DNA of the same individual. This event is the result of losing one allele of a chromosomal region while the other allele is retained, duplicated (uniparental disonomy), or multiplicated (uniparental polysomy). In the same way, chromosomal amplifications can be unbalanced (if only one allele of a chromosomal region is multiplicated) or balanced (if both alleles are multiplicated). Detecting chromosomal abnormalities is important in cancer research as it allows the discovery of chromosomal regions possibly harbouring cancer-related genes such as tumour suppressor genes or oncogenes. It may also be used to identify genomic markers (i.e. chromosomal abnormalities) that may distinguish between clinically important stages in the disease course, e.g. markers of metastasis or markers of treatment response.Single nucleotide polymorphisms (SNPs) account for most of the genetic variation in the
Review of Survey activities 2009: Late Cretaceous basin development of the southern Danish Central Graben
Jakobsen, Finn,Andersen, Claus
Geological Survey of Denmark and Greenland Bulletin , 2010,
A New Experimental Infection Model in Ferrets Based on Aerosolised Mycobacterium bovis
Lyanne McCallan,David Corbett,Peter L. Andersen,Claus Aagaard,David McMurray,Claire Barry,Suzan Thompson,Samuel Strain,Jim McNair
Veterinary Medicine International , 2011, DOI: 10.4061/2011/981410
Abstract: There is significant interest in developing vaccines to control bovine tuberculosis, especially in wildlife species where this disease continues to persist in reservoir species such as the European Badger (Meles meles). However, gaining access to populations of badgers (protected under UK law) is problematic and not always possible. In this study, a new infection model has been developed in ferrets (Mustela furo), a species which is closely related to the badger. Groups of ferrets were infected using a Madison infection chamber and were examined postmortem for the presence of tuberculous lesions and to provide tissue samples for confirmation of Mycobacterium bovis by culture. An infectious dose was defined, that establishes infection within the lungs and associated lymph nodes with subsequent spread to the mesentery lymph nodes. This model, which emphasises respiratory tract infection, will be used to evaluate vaccines for the control of bovine tuberculosis in wildlife species. 1. Introduction The persistence of the bovine tuberculosis problem in cattle and other species on a worldwide basis has led to the reappraisal of control programmes to counter this disease. The current direction for research into the control of bovine TB includes evaluation of vaccines that may be deployed in wildlife populations, including badgers (Meles meles) [1, 2]. This work has been largely driven through an experimental model approach [3]. Despite considerable advances in our understanding of the pathogenesis and immunology of the disease and the impact of vaccination in a range of species, there remains a significant paucity of information relating to vaccine efficacy. Significant advances have been made through the use of M. bovis BCG; yet, some studies reported partial protection in badgers against experimental challenge [3, 4]. There remains a need to evaluate other types of vaccines (protein subunit vaccines for example) that may induce enhanced protection from infection or even boost Mycobacterium bovis (M. bovis) BCG generated immunity [5]. The use of free ranging badgers taken from wildlife populations and held in captivity, to study vaccine efficacy, is problematic, primarily since the badger is a protected species under UK legislation and removal of wild animals for experimentation is very emotive to the public. Using a surrogate species, such as the ferret (Mustela furo), brings a number of advantages that include the availability of animals from licensed suppliers, the capacity to control a number of significant experimental features, and the opportunity to
A Beta-mixture model for dimensionality reduction, sample classification and analysis
Kirsti Laurila, Bodil Oster, Claus L Andersen, Philippe Lamy, Torben Orntoft, Olli Yli-Harja, Carsten Wiuf
BMC Bioinformatics , 2011, DOI: 10.1186/1471-2105-12-215
Abstract: Based on data from colon cancer samples we show that our model captures genome-wide characteristics of methylation patterns. We estimate the parameters of the model and show that they vary between different tissue types. Further, for each methylation probe the posterior probability of a methylation state (low, medium or high) is calculated and the probability that the state is correctly predicted is assessed. We demonstrate that the model can be applied to classify cancer tissue types accurately and that the model provides accessible and easily interpretable data summaries.We have developed a beta-mixture model for methylation microarray data. The model substantially reduces the dimensionality of the data. It can be used for further analysis, such as sample classification or to detect changes in methylation status between different samples and tissues.Interest in understanding the effects of epigenetics in relation to different complex diseases is increasing. One epigenetic mechanism of particular interest is DNA methylation at cytosines in CpG dinucleotides. The methylation patterns of genes may change and these alterations have been shown to be related to complex diseases, such as heart diseases [1], schizophrenia [2] and different cancers [3,4]. In cancer, several methylation changes are detectable at the early stages of cancer or even in pre-cancerous tissues or blood [5,6]. In addition, other methylation alterations have been shown to be specific to cancer type and stage [7,8].High-throughput technologies, such as microarrays and large-scale sequencing, allow genome-wide methylation measurements. Analysis of methylation data requires efficient statistical methods to be able to identify potential methylation biomarkers and differential methylation patterns across sample types. Several methods have been proposed to pinpoint significant methylation differences in patients with cancer and to classify different tissue types. Examples include feature selection method
Evaluation of two commercial global miRNA expression profiling platforms for detection of less abundant miRNAs
Steffen G Jensen, Philippe Lamy, Mads H Rasmussen, Marie S Ostenfeld, Lars Dyrskj?t, Torben F ?rntoft, Claus L Andersen
BMC Genomics , 2011, DOI: 10.1186/1471-2164-12-435
Abstract: Using synthetic miRNA samples and plasma RNA samples spiked with different ratios of 174 synthetic miRNAs we assessed the performance characteristics reproducibility, recovery, specificity, sensitivity and linearity. It was found that while the qRT-PCR based platforms were sufficiently sensitive to reproducibly detect miRNAs at the abundance levels found in human plasma, the array based platform was not. At high miRNA levels both qRT-PCR based platforms performed well in terms of specificity, reproducibility and recovery. At low miRNA levels, as in plasma, the miRCURY platform showed better sensitivity and linearity than the TaqMan platform.For profiling clinical samples with low miRNA abundance, such as plasma samples, the miRCURY platform with its better sensitivity and linearity would probably be superior.microRNAs (miRNAs) are short 20-23 nucleotide long non-coding RNAs that are widely distributed in almost all eukaryotic organisms. They have multiple functions however the main function is believed to be post transcriptional regulation of protein levels [1,2]. While miRNAs are often abundant in tissues, the amount found circulating in body fluids such as plasma and serum is often limited. It has been reported that the total RNA level in plasma is in the range 6-300 ng/ml [3,4] and that the miRNA fraction constitutes only a few percent of this [5]. The mechanisms regulating secretion of miRNA into circulation is still unclear. Reports have shown that while endogenous miRNAs appear stable in plasma/serum exogenous miRNAs are not, and as a result of this it has been suggested that endogenous circulating miRNAs are either encapsulated in microvesicles or bound to RNA-binding proteins in complexes, e.g. Ago2 and NPM1, protecting them from degradation [6-8]. Detailed knowledge of the biological function of circulating miRNA does not exist, however it has been shown that vesicular miRNAs can be transferred from cell to cell and influence the behavior of the recipient c
Development of health and depressive symptoms among Danish adolescents—Socioeconomic differences and effects of life-style  [PDF]
Johan Hviid Andersen, Merete Labriola, Thomas Lund, Claus D. Hansen
Open Journal of Preventive Medicine (OJPM) , 2013, DOI: 10.4236/ojpm.2013.31013
Abstract: While the existence of social inequality in health in childhood as well as among adults is well established, research of mechanisms underlying this inequality is still sparse. The study aim was to report on the development of self-rated health and depressive symptoms from age 15 to18 years in a cohort study of Danish adolescents. Methods: The cohort comprised 3,681 individuals born in 1989, 3058 individuals answered the baseline questionnaire in 2004, and 2400 responded to a follow-up questionnaire in 2007, with 2181 individuals participating in both rounds (59% of the original cohort). Social background information of the participants was derived from a national register. For the analysis two variables indicating change in the two health indicators was computed by subtracting the 2007 levels of the variables from the levels experienced in 2004. Results: After 3 years, mean self-rated health (SRH) deteriorated slightly in adolescents (-0.24; 95% CI = -0.28 to -0.19) across all socioeconomic status (SES) groups and depressive symptoms increased (0.64; 95% CI = 0.52 to 0.75). High household income was protective for decrease in SRH (0.62; 0.43 - 0.91). Negative lifestyle changes were associated with poorer SRH and more depressive symptoms. Conclusions: Self-rated health and depressive symptoms changed to the worse among Danish adolescents from age 15 to 18 years. Negative changes in several lifestyle factors were found to accompany the deterioration of health. This result stresses the intrinsic relationship between lifestyle changes and health and the possible positive effect of maintaining and enhancing positive lifestyle factors.
What is the Clinical Relevance of Follicle-Stimulating Hormone Isoforms in Fertility Treatment?
Claus Yding Andersen and Diego Ezcurra
Reproductive Biology Insights , 2012, DOI: 10.4137/RBI.S7362
Abstract: Follicle-stimulating hormone, both naturally synthesized and as commercial preparations, exists as different isoforms. Variation in the process of glycosylation, particularly in the number of terminal sialic-acid residues, gives rise to isoforms of varying acidic profiles with differences in half-life and bioactivity. Based on the known follicle-stimulating hormone isoform variation across the reproductive cycle, it is possible that the follicle-stimulating hormone isoform profile used in controlled ovarian stimulation may impact follicular recruitment and clinical treatment outcomes. In light of the uncertainty regarding the clinical relevance of follicle-stimulating hormone isoforms in fertility treatment, published studies exploring this topic are reviewed.
The association between genetic variants in hMLH1 and hMSH2 and the development of sporadic colorectal cancer in the Danish population
Lise Christensen, Bo E Madsen, Friedrik P Wikman, Carsten Wiuf, Karen Koed, Anne Tj?nneland, Anja Olsen, Ann-Christine Syv?nen, Claus L Andersen, Torben F ?rntoft
BMC Medical Genetics , 2008, DOI: 10.1186/1471-2350-9-52
Abstract: Associations between genetic variants in hMLH1 and hMSH2 and sporadic colorectal cancer were evaluated using a case-cohort design. The genotyping was performed on DNA isolated from blood from the 380 cases with sporadic colorectal cancer and a sub-cohort of 770 individuals. The DNA samples were analyzed using Single Base Extension (SBE) Tag-arrays. A Bonferroni corrected Fisher exact test was used to test for association between the genotypes of each variant and colorectal cancer. Linkage disequilibrium (LD) was investigated using HaploView (v3.31).Heterozygous and homozygous changes were detected in 13 of 35 analyzed variants. Two variants showed a borderline association with colorectal cancer, whereas the remaining variants demonstrated no association. Furthermore, the genomic regions covering hMLH1 and hMSH2 displayed high linkage disequilibrium in the Danish population. Twenty-two variants were neither detected in the cases with sporadic colorectal cancer nor in the sub-cohort. Some of these rare variants have been classified either as pathogenic mutations or as neutral variants in other populations and some are unclassified Danish variants.None of the variants in hMLH1 and hMSH2 analyzed in the present study were highly associated with colorectal cancer in the Danish population. High linkage disequilibrium in the genomic regions covering hMLH1 and hMSH2, indicate that common genetic variants in the two genes in general are not involved in the development of sporadic colorectal cancer. Nevertheless, some of the rare unclassified variants in hMLH1 and hMSH2 might be involved in the development of colorectal cancer in the families where they were originally identified.Colorectal cancer (CRC) is a common malignant disease in the western world. The lifetime risk is about 5% and rising [1]. In 2003, approximately 3,600 new cases where registered by the Danish Cancer Registry equivalent to 10% of the total number of malignant cancer cases in Denmark, making CRC the th
The Jurassic of Denmark and Greenland: Upper Jurassic – Lower Cretaceous of the Danish Central Graben: structural framework and nomenclature
Japsen, Peter,Britze, Peter,Andersen, Claus
Geological Survey of Denmark and Greenland Bulletin , 2003,
Abstract: The Danish Central Graben is part of the mainly Late Jurassic complex of grabens in the central and southern North Sea which form the Central Graben. The tectonic elements of the Danish Central Graben in the Late Jurassic are outlined and compared to those in the Early Cretaceous based on reduced versions of published maps (1:200 000), compiled on the basis of all 1994 public domain seismic and well data. The Tail End Graben, a half-graben which stretches for about 90 km along the East North Sea High, is the dominant Late Jurassic structural feature. The Rosa Basin (new name) is a narrow, north-south-trending basin extending from the south-western part of the Tail End Graben. The Tail End Graben ceased to exist as a coherent structural element during the Early Cretaceous and developed into three separate depocentres: the Iris and Gulnare Basins to the north and the Roar Basin to the south (new names). The Early Cretaceous saw a shift from subsidence focused along the East North Sea High during the Late Jurassic to a more even distribution of minor basins within the Danish Central Graben. The depth to the top of the Upper Jurassic - lowermost Cretaceous Farsund Formation reaches a maximum of 4800 m in the northern part of the study area, while the depth to the base of the Upper Jurassic reaches 7500 m in the Tail End Graben, where the Upper Jurassic attains a maximum thickness of 3600 m. The Lower Cretaceous Cromer Knoll Group attains a maximum thickness of 1100 m in the Outer Rough Basin.
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