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Exploring the Role of TET2 in Leukemic Cell Biology
No full textT-cell akut lymfatisk leukemi (T-ALL) är en vanlig form av barncancer som ofta medför allvarliga biverkningar och låg överlevnad vid återfall. Detta understryker det stora behovet av nya terapeutiska strategier. Hos barn har T-ALL länkats till epigenetisk nedtystning av promotorregionen för ten-eleven translokation 2 (TET2), vilket leder till inaktivering av genen. Ett flertal studier tyder på att TET2 är en tumörsuppressorgen, och att dess nedtystning genom promotormetylering kan bidra till tumörutveckling. TET2 katalyserar den stegvisa oxidationen av 5-metylcytosin till 5-carboxycytosin via 5-hydroxymethylcytosin. Därmed är det troligt att 5-hydroxymetylcytosin nivåer ökar vid reaktivering av en tystad TET2 gen. En riktad reaktivering av TET2 med hjälp av demetylerande ämnen kan därmedutgöra en lovande framtida behandling för barn med T-ALL. I följande projekt studerades molekylära biologin av TET2 i T-ALL cellinjer. LOUCY celler med CRIPSR/Cas9-medierad TET2 knockout sorterades med hjälp av fluorescensaktiverad cellsortering, och monoklonala pooler validerades genom Sanger sekvensering. Dessa kloner kommer utgöra viktiga kontroller i framtida experiment. Fyra olika masspektrometri protokoll testades för att detektera TET2 proteinet i olika cellinjer. Den kombination som gav högst proteininnehåll totalt och flest kärnproteiner bestod av guanidinium lyseringsbuffert i kombination med peptidnedbrytning via Ultra-FASP. Trots detta kunde TET2 inte identifieras i någotprov. Däremot identifierades TET1 i HEK293T celler när kärnfraktionering kombinerades med Ultra-FASP och guadiniumlysering följt av peptidnedbrytning över natten. För att studera funktionen av TET2 genomfördes en immuno-dot blot analys på DND-41 celler med tystad TET2, efter behandling med GSK3685032 och Vitamin C. Resultaten visade att behandlingen av DND-41 vildtypsceller med GSK3685032 ökade produktionen av 5-hydroxymetylcytosin. Vilket tyder på att TET2 öteruttryckts och är funktionellt aktiv efter behandlingen. Detta bekräftar resultat från tidigare studier och belyser potentialen hos TET2 som en framtida terapeutisk måltavla vid behandling av T-ALL hos barn.T-cell acute lymphoblastic leukaemia (T-ALL) is a common childhood leukaemia with severe side effects and poor relapse survival rates, underscoring the urgent need for new therapeutic strategies. In children, T-ALL has been linked to epigenetic silencing of the ten-eleven translocation 2 (TET2) promoter region, resulting in the inactivation of this gene. Several studies suggest that TET2 functions as a tumour suppressor gene, and silencing this through promoter methylation may contribute to tumour formation. TET2 catalyses the iterative oxidation of 5-methylcytosine to 5 carboxylcytosine via 5-hydroxymethylcytosine, therefore, 5-hydroxymethylcytosine levels should increase upon activation of a silenced TET2 gene. Targeted reactivation of TET2 with the help of demethylating agents could, therefore, be an important future treatment of paediatric T-ALL. In this project, the molecular biologyof TET2 was studied in T-ALL cell lines. Edited LOUCY cells with a CRISPR/Cas9-mediated TET2 knockout were single-cell sorted using Fluorescence-Activated Cell Sorting and monoclonal pools were validated by Sanger Sequencing. These clones will serve as important controls for future experiments. Fourdifferent mass spectrometry protocols were evaluated for the detection of TET2 protein in various cell lines. The guanidinium lysis buffer in combination with peptide digestion using Ultra-FASP, yielded the highest number of proteins and nuclear proteins. TET2 could not be identified in any of the samples, although TET1 was identified in HEK293T cells when performing nuclear fractionation and Ultra-FASP together with guanidinium lysis buffer and overnight digestion. To investigate the function of TET2, immuno-dot blot analysis was used to study the effect of the demethylating agent GSK3685032 and Vitamin C in the TET2-silenced cell line DND-41. Immuno-dot blot analysis revealed that treatment with the demethylating agent GSK3685032 in DND-41 wild-type cell lines increased the production of 5-hydroxymethylcytosine, indicating that the TET2 protein gets re-expressed and is functionally active. The following confirms results from previous studies, highlighting the potential of TET2 as a future drug target in paediatric T-ALL
Exploring the Role of TET2 in Leukemic Cell Biology
No full textT-cell akut lymfatisk leukemi (T-ALL) är en vanlig form av barncancer som ofta medför allvarliga biverkningar och låg överlevnad vid återfall. Detta understryker det stora behovet av nya terapeutiska strategier. Hos barn har T-ALL länkats till epigenetisk nedtystning av promotorregionen för ten-eleven translokation 2 (TET2), vilket leder till inaktivering av genen. Ett flertal studier tyder på att TET2 är en tumörsuppressorgen, och att dess nedtystning genom promotormetylering kan bidra till tumörutveckling. TET2 katalyserar den stegvisa oxidationen av 5-metylcytosin till 5-carboxycytosin via 5-hydroxymethylcytosin. Därmed är det troligt att 5-hydroxymetylcytosin nivåer ökar vid reaktivering av en tystad TET2 gen. En riktad reaktivering av TET2 med hjälp av demetylerande ämnen kan därmedutgöra en lovande framtida behandling för barn med T-ALL. I följande projekt studerades molekylära biologin av TET2 i T-ALL cellinjer. LOUCY celler med CRIPSR/Cas9-medierad TET2 knockout sorterades med hjälp av fluorescensaktiverad cellsortering, och monoklonala pooler validerades genom Sanger sekvensering. Dessa kloner kommer utgöra viktiga kontroller i framtida experiment. Fyra olika masspektrometri protokoll testades för att detektera TET2 proteinet i olika cellinjer. Den kombination som gav högst proteininnehåll totalt och flest kärnproteiner bestod av guanidinium lyseringsbuffert i kombination med peptidnedbrytning via Ultra-FASP. Trots detta kunde TET2 inte identifieras i någotprov. Däremot identifierades TET1 i HEK293T celler när kärnfraktionering kombinerades med Ultra-FASP och guadiniumlysering följt av peptidnedbrytning över natten. För att studera funktionen av TET2 genomfördes en immuno-dot blot analys på DND-41 celler med tystad TET2, efter behandling med GSK3685032 och Vitamin C. Resultaten visade att behandlingen av DND-41 vildtypsceller med GSK3685032 ökade produktionen av 5-hydroxymetylcytosin. Vilket tyder på att TET2 öteruttryckts och är funktionellt aktiv efter behandlingen. Detta bekräftar resultat från tidigare studier och belyser potentialen hos TET2 som en framtida terapeutisk måltavla vid behandling av T-ALL hos barn.T-cell acute lymphoblastic leukaemia (T-ALL) is a common childhood leukaemia with severe side effects and poor relapse survival rates, underscoring the urgent need for new therapeutic strategies. In children, T-ALL has been linked to epigenetic silencing of the ten-eleven translocation 2 (TET2) promoter region, resulting in the inactivation of this gene. Several studies suggest that TET2 functions as a tumour suppressor gene, and silencing this through promoter methylation may contribute to tumour formation. TET2 catalyses the iterative oxidation of 5-methylcytosine to 5 carboxylcytosine via 5-hydroxymethylcytosine, therefore, 5-hydroxymethylcytosine levels should increase upon activation of a silenced TET2 gene. Targeted reactivation of TET2 with the help of demethylating agents could, therefore, be an important future treatment of paediatric T-ALL. In this project, the molecular biologyof TET2 was studied in T-ALL cell lines. Edited LOUCY cells with a CRISPR/Cas9-mediated TET2 knockout were single-cell sorted using Fluorescence-Activated Cell Sorting and monoclonal pools were validated by Sanger Sequencing. These clones will serve as important controls for future experiments. Fourdifferent mass spectrometry protocols were evaluated for the detection of TET2 protein in various cell lines. The guanidinium lysis buffer in combination with peptide digestion using Ultra-FASP, yielded the highest number of proteins and nuclear proteins. TET2 could not be identified in any of the samples, although TET1 was identified in HEK293T cells when performing nuclear fractionation and Ultra-FASP together with guanidinium lysis buffer and overnight digestion. To investigate the function of TET2, immuno-dot blot analysis was used to study the effect of the demethylating agent GSK3685032 and Vitamin C in the TET2-silenced cell line DND-41. Immuno-dot blot analysis revealed that treatment with the demethylating agent GSK3685032 in DND-41 wild-type cell lines increased the production of 5-hydroxymethylcytosine, indicating that the TET2 protein gets re-expressed and is functionally active. The following confirms results from previous studies, highlighting the potential of TET2 as a future drug target in paediatric T-ALL
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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