167 research outputs found
MicroRNA miR-128 represses LINE-1 (L1) retrotransposition by down-regulating the nuclear import factor TNPO1.
Get PDFRepetitive elements, including LINE-1 (L1), comprise approximately half of the human genome. These elements can potentially destabilize the genome by initiating their own replication and reintegration into new sites (retrotransposition). In somatic cells, transcription of L1 elements is repressed by distinct molecular mechanisms, including DNA methylation and histone modifications, to repress transcription. Under conditions of hypomethylation (e.g. in tumor cells), a window of opportunity for L1 derepression arises, and additional restriction mechanisms become crucial. We recently demonstrated that the microRNA miR-128 represses L1 activity by directly binding to L1 ORF2 RNA. In this study, we tested whether miR-128 can also control L1 activity by repressing cellular proteins important for L1 retrotransposition. We found that miR-128 targets the 3' UTR of nuclear import factor transportin 1 (TNPO1) mRNA. Manipulation of miR-128 and TNPO1 levels demonstrated that induction or depletion of TNPO1 affects L1 retrotransposition and nuclear import of an L1-ribonucleoprotein complex (using L1-encoded ORF1p as a proxy for L1-ribonucleoprotein complexes). Moreover, TNPO1 overexpression partially reversed the repressive effect of miR-128 on L1 retrotransposition. Our study represents the first description of a protein factor involved in nuclear import of the L1 element and demonstrates that miR-128 controls L1 activity in somatic cells through two independent mechanisms: direct binding to L1 RNA and regulation of a cellular factor necessary for L1 nuclear import and retrotransposition
A Programmatic Approach to Patient Blood Management – reducing transfusions and improving patient outcomes
Get PDFIn July 2008, the Western Australia (WA) Department of Health embarked on a landmark 5-year project to implement a sustainable comprehensive health-system-wide Patient Blood Management Program. Fundamentally, it was a quality and safety initiative, which also had profound resource and economic implications. Unsustainable escalating direct and indirect costs of blood, potentially severe blood shortages due to changing population dynamics, donor deferrals, loss of altruism, wide variations in transfusion practice and growing knowledge of transfusion limitations and adverse outcomes necessitate a paradigm shift in the management of anemia and blood loss. The concept of patient-focused blood management is proving to be an effective force for change. This approach has now evolved to embrace comprehensive hospital-wide Patient Blood Management Programs. These programs show significant reductions in blood utilisation, reduced costs while achieving similar or improved patient outcomes. The WA Program is achieving these outcomes across a health jurisdiction in a sustained manner
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