55 research outputs found
Endonuclease-independent LINE-1 retrotransposition at mammalian telomeres
Long interspersed element-1 (LINE-1 or L1) elements are abundant, non-long-terminal-repeat (non-LTR) retrotransposons that comprise 17% of human DNA(1). The average human genome contains similar to 80-100 retrotransposition- competent L1s (ref. 2), and they mobilize by a process that uses both the L1 endonuclease and reverse transcriptase, termed target-site primed reverse transcription(3-5). We have previously reported an efficient, endonuclease-independent L1 retrotransposition pathway (ENi) in certain Chinese hamster ovary (CHO) cell lines that are defective in the non-homologous end-joining (NHEJ) pathway of DNA double-strand-break repair(6). Here we have characterized ENi retrotransposition events generated in V3 CHO cells, which are deficient in DNA-dependent protein kinase catalytic subunit (DNA-PKcs) activity and have both dysfunctional telomeres and an NHEJ defect. Notably, similar to 30% of ENi retrotransposition events insert in an orientation-specific manner adjacent to a perfect telomere repeat (5'-TTAGGG-3'). Similar insertions were not detected among ENi retrotransposition events generated in controls or in XR-1 CHO cells deficient for XRCC4, an NHEJ factor that is required for DNA ligation but has no known function in telomere maintenance. Furthermore, transient expression of a dominant-negative allele of human TRF2 ( also called TERF2) in XRCC4-deficient XR-1 cells, which disrupts telomere capping, enables telomere-associated ENi retrotransposition events. These data indicate that L1s containing a disabled endonuclease can use dysfunctional telomeres as an integration substrate. The findings highlight similarities between the mechanism of ENi retrotransposition and the action of telomerase, because both processes can use a 3' OH for priming reverse transcription at either internal DNA lesions or chromosome ends(7,8). Thus, we propose that ENi retrotransposition is an ancestral mechanism of RNA-mediated DNA repair associated with non-LTR retrotransposons that may have been used before the acquisition of an endonuclease domain.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62964/1/nature05560.pd
The contribution of metacognitions and attentional control to decisional procrastination
Earlier research has implicated metacognitions and attentional control in procrastination and self-regulatory failure. This study tested several hypotheses: (1) that metacognitions would be positively correlated with decisional procrastination; (2) that attentional control would be negatively correlated with decisional procrastination; (3) that metacognitions would be negatively correlated with attentional control; and (4) that metacognitions and attentional control would predict decisional procrastination when controlling for negative affect. One hundred and twenty-nine participants completed the Depression Anxiety Stress Scale 21, the Meta-Cognitions Questionnaire 30, the Attentional Control Scale, and the Decisional Procrastination Scale. Significant relationships were found between all three attentional control factors (focusing, shifting, and flexible control of thought) and two metacognitions factors (negative beliefs concerning thoughts about uncontrollability and danger, and cognitive confidence). Results also revealed that decisional procrastination was significantly associated with negative affect, all measured metacognitions factors, and all attentional control factors. In the final step of a hierarchical regression analysis only stress, cognitive confidence, and attention shifting were independent predictors of decisional procrastination. Overall these findings support the hypotheses and are consistent with the Self-Regulatory Executive Function model of psychological dysfunction. The implications of these findings are discussed
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Synthesis of guidance available for assessing methodological quality and grading of evidence from qualitative research to inform clinical recommendations: a systematic literature review.
OBJECTIVE: To understand (1) what guidance exists to assess the methodological quality of qualitative research; (2) what methods exist to grade levels of evidence from qualitative research to inform recommendations within European Alliance of Associations for Rheumatology (EULAR). METHODS: A systematic literature review was performed in multiple databases including PubMed/Medline, EMBASE, Web of Science, COCHRANE and PsycINFO, from inception to 23 October 2020. Eligible studies included primary articles and guideline documents available in English, describing the: (1) development; (2) application of validated tools (eg, checklists); (3) guidance on assessing methodological quality of qualitative research and (4) guidance on grading levels of qualitative evidence. A narrative synthesis was conducted to identify key similarities between included studies. RESULTS: Of 9073 records retrieved, 51 went through to full-manuscript review, with 15 selected for inclusion. Six articles described methodological tools to assess the quality of qualitative research. The tools evaluated research design, recruitment, ethical rigour, data collection and analysis. Seven articles described one approach, focusing on four key components to determine how much confidence to place in findings from systematic reviews of qualitative research. Two articles focused on grading levels of clinical recommendations based on qualitative evidence; one described a qualitative evidence hierarchy, and another a research pyramid. CONCLUSION: There is a lack of consensus on the use of tools, checklists and approaches suitable for appraising the methodological quality of qualitative research and the grading of qualitative evidence to inform clinical practice. This work is expected to facilitate the inclusion of qualitative evidence in the process of developing recommendations at EULAR level
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