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Search Results: 1 - 10 of 2586 matches for " Lise Lotte Christensen "
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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.
Intertwining caring science, caring practice and caring education from a lifeworld perspective—two contextual examples
Ulrica H?rberg,Lise-lotte Ozolins,Margaretha Ekebergh
International Journal of Qualitative Studies on Health & Well-Being , 2011, DOI: 10.3402/qhw.v6i4.10363
Abstract: This article describes how caring science can be a helpful foundation for caring practice and what kind of learning support that can enable the transformation of caring science into practice. The lifeworld approach is fundamental for both caring and learning. This will be illustrated in two examples from research that show the potential for promoting health and well-being as well as the learning process. One example is from a caring context and the other is from a learning context. In this article, learning and caring are understood as parallel processes. We emphasize that learning cannot be separated from life and thus caring and education is intertwined with caring science and life. The examples illustrate how an understanding of the intertwining can be fruitful in different contexts. The challenge is to implant a lifeworld-based approach on caring and learning that can lead to strategies that in a more profound way have the potential to strengthen the person's health and learning processes.
Merging galaxies produce outliers from the Fundamental Metallicity Relation
Asger Gr?nnow,Kristian Finlator,Lise Christensen
Physics , 2015, DOI: 10.1093/mnras/stv1232
Abstract: From a large sample of $\approx 170,000$ local SDSS galaxies, we find that the Fundamental Metallicity Relation (FMR) has an overabundance of outliers, compared to what would be expected from a Gaussian distribution of residuals, with significantly lower metallicities than predicted from their stellar mass and star formation rate (SFR). This low-metallicity population has lower stellar masses, bimodial specific SFRs with enhanced star formation within the aperture and smaller half-light radii than the general sample, and is hence a physically distinct population. We show that they are consistent with being galaxies that are merging or have recently merged with a satellite galaxy. In this scenario, low-metallicity gas flows in from large radii, diluting the metallicity of star-forming regions and enhancing the specific SFR until the inflowing gas is processed and the metallicity has recovered. We introduce a simple model in which mergers with a mass ratio larger than a minimum dilute the central galaxy's metallicity by an amount that is proportional to the stellar mass ratio for a constant time, and show that it provides an excellent fit to the distribution of FMR residuals. We find the dilution time-scale to be $\tau=1.568_{-0.027}^{+0.029}$ Gyr, the average metallicity depression caused by a 1:1 merger to be $\alpha=0.2480_{-0.0020}^{+0.0017}$ dex and the minimum mass ratio merger that can be discerned from the intrinsic Gaussian scatter in the FMR to be $\xi_\text{min}=0.2030_{-0.0095}^{+0.0127}$ (these are statistical errors only). From this we derive that the average metallicity depression caused by a merger with mass ratio between 1:5 and 1:1 is 0.114 dex.
Knockdown of SF-1 and RNF31 Affects Components of Steroidogenesis, TGFβ, and Wnt/β-catenin Signaling in Adrenocortical Carcinoma Cells
Anna Ehrlund, Philip Jonsson, Lise-Lotte Vedin, Cecilia Williams, Jan-?ke Gustafsson, Eckardt Treuter
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0032080
Abstract: The orphan nuclear receptor Steroidogenic Factor-1 (SF-1, NR5A1) is a critical regulator of development and homeostasis of the adrenal cortex and gonads. We recently showed that a complex containing E3 ubiquitin ligase RNF31 and the known SF-1 corepressor DAX-1 (NR0B1) interacts with SF-1 on target promoters and represses transcription of steroidogenic acute regulatory protein (StAR) and aromatase (CYP19) genes. To further evaluate the role of SF-1 in the adrenal cortex and the involvement of RNF31 in SF-1-dependent pathways, we performed genome-wide gene-expression analysis of adrenocortical NCI-H295R cells where SF-1 or RNF31 had been knocked down using RNA interference. We find RNF31 to be deeply connected to cholesterol metabolism and steroid hormone synthesis, strengthening its role as an SF-1 coregulator. We also find intriguing evidence of negative crosstalk between SF-1 and both transforming growth factor (TGF) β and Wnt/β-catenin signaling. This crosstalk could be of importance for adrenogonadal development, maintenance of adrenocortical progenitor cells and the development of adrenocortical carcinoma. Finally, the SF-1 gene profile can be used to distinguish malignant from benign adrenocortical tumors, a finding that implicates SF-1 in the development of malignant adrenocortical carcinoma.
Screening of Agelasine D and Analogs for Inhibitory Activity against Pathogenic Protozoa; Identification of Hits for Visceral Leishmaniasis and Chagas Disease
Anders Vik,ágnes Proszenyák,Marieke Vermeersch,Paul Cos,Louis Maes,Lise-Lotte Gundersen
Molecules , 2009, DOI: 10.3390/molecules14010279
Abstract: There is an urgent need for novel and improved drugs against several tropical diseases caused by protozoa. The marine sponge (Agelas sp.) metabolite agelasine D, as well as other agelasine analogs and related structures were screened for inhibitory activity against Plasmodium falciparum, Leishmania infantum, Trypanosoma brucei and T. cruzi, as well as for toxicity against MRC-5 fibroblast cells. Many compounds displayed high general toxicity towards both the protozoa and MRC-5 cells. However, two compounds exhibited more selective inhibitory activity against L. infantum (IC50 <0.5 mg/mL) while two others displayed IC50 <1 mg/mL against T. cruzi in combination with relatively low toxicity against MRC-5 cells. According to criteria set up by the WHO Special Programme for Research & Training in Tropical Diseases (TDR), these compounds could be classified as hits for leishmaniasisand for Chagas disease, respectively. Identification of the hits as well as other SAR data from this initial screening will be valuable for design of more potent and selective potential drugs against these neglected tropical diseases.
Using Supplemental Instruction to Bridge the Transition from Secondary to Tertiary Education
Joakim Malm,Lise-Lotte M?rner,Leif Bryngfors,Gunilla Edman
International Journal of Education , 2012, DOI: 10.5296/ije.v4i3.1826
Abstract: Supplemental Instruction (SI) is today a well known academic assistance program, providing help for students in “difficult” courses at colleges and universities. Little attention has been paid however to the possibility of also implementing the SI program in upper secondary school. In this study we present qualitative results from such an SI program in a Swedish setting. Here, students from the faculty of engineering at Lund University, act as SI leaders at eleven upper secondary schools in the local region, in subjects such as math, physics and chemistry. The main conclusion is that the SI methodology also seems to work in an upper secondary school environment. The students who attend SI regularly appear to obtain new study strategies to increase their understanding of the subject, besides improving on general skills such as teamwork, communicating on a subject, and making presentations in front of others. There are several advantages for the schools and university involved. For example they gain a formal and an informal link, which can prove useful in many circumstances when an exchange of information is needed, and both can use SI as a means to boost recruitment. For the upper secondary school, the students can get an alternative view on subjects, which hopefully stimulates interest and understanding. The students also get a more mature role model to turn to. For the university an additional advantage is that a more informal view of what it is like to study at university can be provided to upper secondary school students.
Functional recombinant MHC class II molecules and high-throughput peptide-binding assays
Justesen Sune,Harndahl Mikkel,Lamberth Kasper,Nielsen Lise-Lotte B
Immunome Research , 2009, DOI: 10.1186/1745-7580-5-2
Abstract: Background Molecules of the class II major histocompability complex (MHC-II) specifically bind and present exogenously derived peptide epitopes to CD4+ T helper cells. The extreme polymorphism of the MHC-II hampers the complete analysis of peptide binding. It is also a significant hurdle in the generation of MHC-II molecules as reagents to study and manipulate specific T helper cell responses. Methods to generate functional MHC-II molecules recombinantly, and measure their interaction with peptides, would be highly desirable; however, no consensus methodology has yet emerged. Results We generated α and β MHC-II chain constructs, where the membrane-spanning regions were replaced by dimerization motifs, and the C-terminal of the β chains was fused to a biotinylation signal peptide (BSP) allowing for in vivo biotinylation. These chains were produced separately as inclusion bodies in E. coli , extracted into urea, and purified under denaturing and non-reducing conditions using conventional column chromatography. Subsequently, diluting the two chains into a folding reaction with appropriate peptide resulted in efficient peptide-MHC-II complex formation. Several different formats of peptide-binding assay were developed including a homogeneous, non-radioactive, high-throughput (HTS) binding assay. Binding isotherms were generated allowing the affinities of interaction to be determined. The affinities of the best binders were found to be in the low nanomolar range. Recombinant MHC-II molecules and accompanying HTS peptide-binding assay were successfully developed for nine different MHC-II molecules including the DPA1*0103/DPB1*0401 (DP401) and DQA1*0501/DQB1*0201, where both α and β chains are polymorphic, illustrating the advantages of producing the two chains separately. Conclusion We have successfully developed versatile MHC-II resources, which may assist in the generation of MHC class II -wide reagents, data, and tools.
Victim-Offender Mediation: Observations from Scandinavia
Mari-Louise Pabsdorff,Lise-Lotte Rytterbro,Saija Sambou,Erika Uotila
O?ati Socio-Legal Series , 2011,
Abstract: Mediation in the aftermath of conflicts and crimes is getting more common in the European countries. This study analyses the discourse between the parties and mediator(s) during mediation in three Scandinavian countries. Mediation talk is much concentrated on the crime situation, on the actions of the parties and other persons present at the time of the crime. Central to the discourse is “accounts”; an analytical term developed by Scott and Lyman in the 1960’s. Explanations of the crime are primarily found on an individual level, leaving societal issues out: A normative and evaluative inquiry of crimes and why crimes occur play a minimal (if any) role in VOM in Scandinavia. DOWNLOAD THIS PAPER FROM SSRN: http://ssrn.com/abstract=1737385
Corroborating indicates nurses’ ethical values in a geriatric ward
Lise-Lotte Jonasson,Per-Erik Liss,Bj?rn Westerlind,Carina Berter?
International Journal of Qualitative Studies on Health & Well-Being , 2011, DOI: 10.3402/qhw.v6i3.7291
Abstract: The aim of the study was to identify nurses’ ethical values, which become apparent through their behaviour in the interactions with older patients in caring encounters at a geriatric clinic.Descriptions of ethics in a caring practice are a problem since they are vague compared with the four principles of autonomy, beneficence, non-maleficence, and justice.A Grounded Theory methodology was used. In total, 65 observations and follow-up interviews with 20 nurses were conducted, and data were analysed by constant comparative analysis. Three categories were identified: showing consideration, connecting, and caring for. These categories formed the basis of the core category: “Corroborating.” In corroborating, the focus is on the person in need of integrity and self-determination; that is, the autonomy principle. A similar concept was earlier described in regard to confirming. Corroborating deals more with support and interaction. It is not enough to be kind and show consideration (i.e., to benefit someone); nurses must also connect and care for the older person (i.e., demonstrate non-maleficence) in order to corroborate that person.The findings of this study can improve the ethics of nursing care. There is a need for research on development of a high standard of nursing care to corroborate the older patients in order to maintain their autonomy, beneficence, and non-maleficence. The principal of justice was not specifically identified as a visible nursing action. However, all older patients received treatment, care, and reception in an equivalent manner.
The Association of Alcohol and Alcohol Metabolizing Gene Variants with Diabetes and Coronary Heart Disease Risk Factors in a White Population
Lise Lotte N. Husemoen,Torben J?rgensen,Knut Borch-Johnsen,Torben Hansen,Oluf Pedersen,Allan Linneberg
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0011735
Abstract: Epidemiological studies have shown a J- or U-shaped relation between alcohol and type 2 diabetes and coronary heart disease (CHD). The underlying mechanisms are not clear. The aim was to examine the association between alcohol intake and diabetes and intermediate CHD risk factors in relation to selected ADH and ALDH gene variants.
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