54 research outputs found

    A novel long non-coding RNA from NBL2 pericentromeric macrosatellite forms a perinucleolar aggregate structure in colon cancer

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    Primate-specific NBL2 macrosatellite is hypomethylated in several types of tumors, yet the consequences of this DNA hypomethylation remain unknown. We show that NBL2 conserved repeats are close to the centromeres of most acrocentric chromosomes. NBL2 associates with the perinucleolar region and undergoes severe demethylation in a subset of colorectal cancer (CRC). Upon DNA hypomethylation and histone acetylation, NBL2 repeats are transcribed in tumor cell lines and primary CRCs. NBL2 monomers exhibit promoter activity, and are contained within novel, non-polyA antisense lncRNAs, which we designated TNBL (Tumor-associated NBL2 transcript). TNBL is stable throughout the mitotic cycle, and in interphase nuclei preferentially forms a perinucleolar aggregate in the proximity of a subset of NBL2 loci. TNBL aggregates interact with the SAM68 perinucleolar body in a mirror-image cancer specific perinucleolar structure. TNBL binds with high affinity to several proteins involved in nuclear functions and RNA metabolism, such as CELF1 and NPM1. Our data unveil novel DNA and RNA structural features of a non-coding macrosatellite frequently altered in cancer

    Helicase Lymphoid-specific enzyme contributes to the maintenance of methylation of SST1 pericentromeric repeats that are frequently demethylated in colon cancer and associated with genomic damage

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    DNA hypomethylation at repetitive elements accounts for the genome-wide DNA hypomethylation common in cancer, including colorectal cancer (CRC). We identified a pericentromeric repeat element called SST1 frequently hypomethylated (>5% demethylation compared with matched normal tissue) in several cancers, including 28 of 128 (22%) CRCs. SST1 somatic demethylation associated with genome damage, especially in tumors with wild-type TP53. Seven percent of the 128 CRCs exhibited a higher ("severe") level of demethylation (≄10%) that co-occurred with TP53 mutations. SST1 demethylation correlated with distinct histone marks in CRC cell lines and primary tumors: demethylated SST1 associated with high levels of the repressive histone 3 lysine 27 trimethylation (H3K27me3) mark and lower levels of histone 3 lysine 9 trimethylation (H3K9me3). Furthermore, induced demethylation of SST1 by 5-aza-dC led to increased H3K27me3 and reduced H3K9me3. Thus, in some CRCs, SST1 demethylation reflects an epigenetic reprogramming associated with changes in chromatin structure that may affect chromosomal integrity. The chromatin remodeler factor, the helicase lymphoid-specific (HELLS) enzyme, called the "epigenetic guardian of repetitive elements", interacted with SST1 as shown by chromatin immunoprecipitation, and down-regulation of HELLS by shRNA resulted in demethylation of SST1 in vitro. Altogether these results suggest that HELLS contributes to SST1 methylation maintenance. Alterations in HELLS recruitment and function could contribute to the somatic demethylation of SST1 repeat elements undergone before and/or during CRC pathogenesis

    Computational Methods for Protein Identification from Mass Spectrometry Data

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    Protein identification using mass spectrometry is an indispensable computational tool in the life sciences. A dramatic increase in the use of proteomic strategies to understand the biology of living systems generates an ongoing need for more effective, efficient, and accurate computational methods for protein identification. A wide range of computational methods, each with various implementations, are available to complement different proteomic approaches. A solid knowledge of the range of algorithms available and, more critically, the accuracy and effectiveness of these techniques is essential to ensure as many of the proteins as possible, within any particular experiment, are correctly identified. Here, we undertake a systematic review of the currently available methods and algorithms for interpreting, managing, and analyzing biological data associated with protein identification. We summarize the advances in computational solutions as they have responded to corresponding advances in mass spectrometry hardware. The evolution of scoring algorithms and metrics for automated protein identification are also discussed with a focus on the relative performance of different techniques. We also consider the relative advantages and limitations of different techniques in particular biological contexts. Finally, we present our perspective on future developments in the area of computational protein identification by considering the most recent literature on new and promising approaches to the problem as well as identifying areas yet to be explored and the potential application of methods from other areas of computational biology

    Mitt barn har cancer - En litteraturöversikt över förÀldrars upplevelser av att leva med ett cancersjukt barn

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    Bakgrund: I Sverige insjuknar cirka 300 barn och ungdomar varje Är i nÄgon form av cancersjukdom och cancer Àr den vanligaste dödsorsaken för barn under 15 Är. NÀr nÄgon i en familj blir sjuk sÄ pÄverkar det hela familjen. DÀrför handlar familjecentrerad omvÄrdnad om att se familjen som en helhet. Det innebÀr ett lidande att bli sjuk och lidandet behöver hopp och mening för att kunna genomlidas. För att kunna ge bra vÄrd till barnen behöver vÄrdpersonalen skapa ett bra samarbete med förÀldrarna och fÄ förÀldrarna att vara delaktiga i omvÄrdnaden. Genom kunskap om hur förÀldrarna upplever sin situation kan sjuksköterskor ge ett bra bemötande till dem. Syfte: Att beskriva hur förÀldrar upplever sin livssituation av att leva med ett cancersjukt barn. Metod: En litteraturöversikt baserad pÄ internationell forskning frÄn Ären 2010-2015. BÄde kvalitativa och kvantitativa artiklar har anvÀnts. Resultat: Resultatet presenteras i tre olika övergripande teman; att uppleva stöd frÄn vÄrdpersonal, att leva i vardagen och att finna kraft för att orka. Slutsats: NÀr ett barn drabbas av cancer pÄverkar den hela familjen och förÀldrarnas liv vÀnds upp och ner. Alla aspekter pÄverkas; vardagslivet, familjelivet, parrelationen, arbetssituationen, ekonomin och förÀldrarnas fysiska och psykiska hÀlsa. FörÀldrarna kan behöva stöd frÄn familj, vÀnner, arbetsplats, barnets skola, religion, hopp och frÄn sjukhuset för att kunna ta sig igenom situationen. Sjuksköterskor kan genom att ge stöd, information, samtal och undervisning möta förÀldrarna i deras lidande och hjÀlpa dem att finna hopp

    Visualization of Regional Liver Function with Hepatobiliary Contrast Agent Gd-EOB-DTPA

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    Liver biopsy is a very common, but invasive procedure for diagnosing liver disease. However, such a biopsy may result in severe complications and in some cases even death. Therefore, it would be highly desirable to develop a non-invasive method which would provide the same amount of information on staging of the disease and also the location of pathologies. This thesis describes the implementation of such a non-invasive method for visualizing and quantifying liver function by the combination of MRI (Magnetic Resonance Imaging), image reconstruction, and image analysis, and pharmacokinetic modeling. The first attempt involved automatic segmentation, functional clustering (k-means) and classification (kNN) of in-data (liver, spleen and blood vessel segments) in the pharmacokinetic model. However, after implementing and analyzing this method some important issues were identified and the image segmentation method was therefore revised. The segmentation method that was subsequently developed involved a semi-automatic procedure, based on a modified image forest transform (IFT). The data were then simulated and optimized using a pharmacokinetic model describing the pharmacokinetics of the liver specific contrast agent Gd-EOB-DTPA in the human body. The output from the modeling procedure was then further analyzed, using a least-squares method, in order to assess liver function by estimating the fractions of hepatocytes, extracellular extravascular space (EES) and blood plasma in each voxel of the image. The result were in fair agreement with literature values, although further analyses and developments will be required in order to validate and also to confirm the accuracy of the method

    Ideals and Practice : A case study of the youth library PUNKTmedis in relation to the Swedish Library Act

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    This two-year master thesis aims to examine how the Swedish Library Act affects the youth library PUNKTmedis and its librarians. Through a case study and by using a socio-cultural and a norm critical perspective, the study discusses three main questions: 1. How do the librarians view the new law and how do they apply its new directives at PUNKTmedis? 2. Have they made any changes to the planning and execution of reading promotion activities since the law came into force? What activities are there currently in the library and how are they considered to promote reading? How does the library work with a broader literary concept and a broader view of what reading is? 3. How do the librarians at PUNKTmedis work with the assignment to give special attention to children and young people to promote their reading, with their specific focus on girls who already read, especially since research and reports all too often lifts boys' reading as waning? How deeply rooted is the librarians’ commitment? The study finds that the effect the Library Act has on PUNKTmedis is that it inspires the work of the librarians, due to formulations such as a “broader literacy concept” and the ability to work with different formats regarding the media in the library. The library offers many different reading promotional activities due to this. But the library has not really changed their way work since the new law was enforced, which might be because they are a youth library and don’t need to be as traditional as a regular public library. In addition to that, the librarians feel that the law is rather weak. Regarding to how the librarians at PUNKTmedis work with the assignment to promote reading, the study finds that the librarians try to work towards the individual, but by having a profile towards girls who already like to read, they make them visible in contrast to the boy norm.

    Solkatt

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    Solkatt Àr ett arbete inom textildesign som undersöker hur vÀvd shibori kan anvÀndas i en textil utsmyckning. Arbetet vidareutvecklar en förstudie, i vilken tekniken vÀvd shibori undersöktes genom handvÀvning, frÄn materialundersökning till design, genom industriell vÀvning. De mönstrade strukturerna skapas av extra mönstertrÄdar som vÀvs med krympgarn. Textilierna Àr inspirerade av solkatter; hur det intensiva ljuset dansar, reflekteras och blÀnker. Strukturernas uttryck förstÀrks i tvÄ steg, först med folietryck och dÀrefter med ljussÀttning. Resultatet Àr en textil utsmyckning som leker med ljuset. Den har formen av en halvcirkel dÀr folien Àr tryckt pÄ insidan av formen. LjussÀttningen förstÀrker den mönstrade strukturen.Engelsk titel: SolkattProgram: Textile Desig

    The open records system : patients' experiences of reading their medical records

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    Bakgrund Sedan en tid tillbaka har webbÄtkomst av patientjournalen utvecklats och blivit möjlig för patienterna sÄvÀl i Sverige som i flera lÀnder globalt. Sedan tillgÄngen till journalen underlÀttats för patienterna tar allt fler chansen att lÀsa i sina journaler. Med bakgrund av detta undersöks patienternas upplevelser och erfarenheter av att lÀsa sina journaler i denna litteraturstudie.  Syfte Syftet var att belysa vuxna patienters upplevelser av att lÀsa journalen vid kontakt med hÀlso- och sjukvÄrden. Metod En icke-systematisk litteraturöversikt genomfördes genom att samla in data och granska 17 vetenskapliga originalartiklar. Artiklarna innefattar varierande typer av studiedesign. Författarna granskade de utvalda originalartiklarna efter Sophiahemmets Högskolas bedömningsunderlag för kvalitetsgranskning, för att sedan analysera artiklarna genom en integrerad analysmetod. Utefter detta presenterades resultatet uppdelat efter tre teman som författarna fann under analysen.  Resultat Genom granskningen upptÀcktes tre huvudteman. De teman som upptÀcktes dÄ patienternas upplevelser av att lÀsa sina journaler undersöktes var: Patienternas upplevelse av: patientdelaktighet, av att inhÀmta, tolka och förstÄ journalinformation och personcentrering. Under dessa huvudkategorier sÄgs ett antal subteman. Dessa subteman innefattade patienternas upplevelser av eller kring deltagande, kommunikation, medicinsk terminologi, förstÄelse, tekniska svÄrigheter, reaktioner och kÀnslor, partnerskapet, egenmakt och egenvÄrd. Slutsats Enligt studien var patienterna till stor del positiva över tillgÄngen till patientjournalen och ville lÀsa sina journalanteckningar. Skillnader fanns mellan olika grupper av patienter nÀr det kom till vilka som tyckte sig ha mest nytta av att lÀsa journalerna. Patienterna upplevde sprÄkbruket och den medicinska terminologin som anvÀnds i journalen som svÄrt att förstÄ. Enligt studien kan en ökad personcentrering och patientdelaktighet, vid och kring journalföringen, leda till positiva erfarenheter hos patienterna sÄvÀl som det kan ge minskade risker inom vÄrden. En ökad personcentrering vid journalföring kan Àven bidra till att stÀrka patienternas möjligheter till ett högre mÄtt av hÀlsolitteracitet.Background For some time now, web access to the medical records has developed and become possible for patients both in Sweden and in several countries globally. Since access to medical records has been made easier for patients, more and more people are taking the chance to read their medical records. Against this background, the patients attitudes and experiences of reading their medical records are examined in this litteraturestudy. Aim The aim was to shed light on adult patients' experience of reading their medical record when in contact with the health care system. Method The authors created a non-systematic literature review by collecting data and reviewing 17 scientific articles. The articles included were of various types. The authors reviewed the selected articles according to Sophiahemmet University's assessment document for quality review and then analyzed the articles through an integrated analysis method. Following this, the results were presented divided according to three themes that the authors found during the analysis. Results Through the review, three main themes were discovered. The themes that were discovered when the patients' experiences of reading their medical records were examined were: The patients' experience of: patient participation, of obtaining, interpreting and understanding medical record information and person-centeredness. Under these main categories, several sub-themes were seen. These sub-themes included the patients' experiences of or around participation, communication, medical terminology, understanding, technical difficulties, reactions and feelings, the partnership, empowerment and self-care. Conclusions According to the study, patients for the most part had positive experiences while reading their medical records and wanted to continue doing so. There were differences between groups of patients when it came to who found that they had the most benefit from reading the medical records. The patients found the language and medical terminology used in the medical record difficult to understand. According to the study, increased person-centredness and patient participation in record keeping can lead to increased positive experiences for patients as well as reduced risks in care. An increased person-centredness in recordkeeping can also contribute to strengthening patients' opportunities for a higher measure of health literacy
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