3,219 research outputs found

    Epigenetic inactivation of miR-9 family microRNAs in chronic lymphocytic leukemia--implications on constitutive activation of NFκB pathway.

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    Background: The miR-9 family microRNAs have been identified as a tumor suppressor miRNA in cancers. We postulated that miR-9-1, miR-9-2 and miR-9-3 might be inactivated by DNA hypermethylation in chronic lymphocytic leukemia (CLL).Methods: Methylation of miR-9-1, miR-9-2 and miR-9-3 was studied in eight normal controls including normal bone marrow, buffy coat, and CD19-sorted peripheral blood B-cells from healthy individuals, seven CLL cell lines, and seventy-eight diagnostic CLL samples by methylation-specific polymerase chain reaction.Results: The promoters of miR-9-3 and miR-9-1 were both unmethylated in normal controls, but methylated in five (71.4%) and one of seven CLL cell lines respectively. However, miR-9-2 promoter was methylated in normal controls including CD19 + ve B-cells, hence suggestive of a tissue-specific but not tumor-specific methylation, and thus not further studied. Different MSP statuses of miR-9-3, including complete methylation, partial methylation, and complete unmethylation, were verified by quantitative bisulfite methylation analysis. 5-Aza-2′-deoxycytidine treatment resulted in miR-9-3 promoter demethylation and re-expression of pri-miR-9-3 in I83-E95 and WAC3CD5+ cells, which were homozygously methylated for miR-9-3. Moreover, overexpression of miR-9 led to suppressed cell proliferation and enhanced apoptosis together with downregulation of NFκB1 in I83-E95 cells, supporting a tumor suppressor role of miR-9-3 in CLL. In primary CLL samples, miR-9-3 was detected in 17% and miR-9-1 methylation in none of the patients at diagnosis. Moreover, miR-9-3 methylation was associated with advanced Rai stage (≥ stage 2) (P = 0.04).Conclusions: Of the miR-9 family, miR-9-3 is a tumor suppressor miRNA relatively frequently methylated, and hence silenced in CLL; whereas miR-9-1 methylation is rare in CLL. The role of miR-9-3 methylation in the constitutive activation of NFκB signaling pathway in CLL warrants further study

    sj-docx-1-pom-10.1177_03057356231159194 – Supplemental material for A cognitive intervention to correct a maladaptive technique in organists due to prior music learning: A randomized controlled trial

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    Supplemental material, sj-docx-1-pom-10.1177_03057356231159194 for A cognitive intervention to correct a maladaptive technique in organists due to prior music learning: A randomized controlled trial by Mandy MP Kan, Nicola Dibben and Arnold YL Wong in Psychology of Music</p

    Rapid and Efficient Synthesis of 1<i>H</i>-Indol-2-yl-1<i>H</i>-quinolin-2-ones

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    A concise and efficient synthesis of the novel indol-2-yl-1H-quinolin-2-one ring system found in the potent and selective KDR kinase inhibitors 1−3 is presented

    Utilizing the principles of Gagne&rsquo;s nine events of instruction in the teaching of Goldmann Applanation Tonometry

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    Yee Ling Wong Ophthalmology Department, Ninewells Hospital and Medical School, Dundee, UK Abstract: Intraocular pressure measurement is important to identify people who are at risk of glaucoma. Goldmann Applanation Tonometry is considered the gold standard with regards to evaluating patients with glaucoma, a sight-threatening condition. The professional execution of this evaluation is critical in the reduction of associated complication rates. This article seeks to put forward a structured lesson plan for ophthalmology trainees, specialist nurses, and optometrists, which integrates Gagne&rsquo;s nine events of instruction to accomplish this objective. Keywords: IOP, Gagne&rsquo;s model, lesson plan, Peyton&rsquo;s steps, glaucoma, ophthalmology teachin

    sj-pdf-1-pmj-10.1177_02692163211049309 – Supplemental material for Pain assessment tools in paediatric palliative care: A systematic review of psychometric properties and recommendations for clinical practice

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    Supplemental material, sj-pdf-1-pmj-10.1177_02692163211049309 for Pain assessment tools in paediatric palliative care: A systematic review of psychometric properties and recommendations for clinical practice by Adrienne YL Chan, Mengqin Ge, Emily Harrop, Margaret Johnson, Kate Oulton, Simon S Skene, Ian CK Wong, Liz Jamieson, Richard F Howard and Christina Liossi in Palliative Medicine</p

    sj-pdf-2-pmj-10.1177_02692163211049309 – Supplemental material for Pain assessment tools in paediatric palliative care: A systematic review of psychometric properties and recommendations for clinical practice

    No full text
    Supplemental material, sj-pdf-2-pmj-10.1177_02692163211049309 for Pain assessment tools in paediatric palliative care: A systematic review of psychometric properties and recommendations for clinical practice by Adrienne YL Chan, Mengqin Ge, Emily Harrop, Margaret Johnson, Kate Oulton, Simon S Skene, Ian CK Wong, Liz Jamieson, Richard F Howard and Christina Liossi in Palliative Medicine</p
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