| 1. |
- Carr, Tiffany, et al.
(författare)
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Oncogenic and Tumor Suppressor Functions for Lymphoid Enhancer Factor 1 in E2a-/- T Acute Lymphoblastic Leukemia
- 2022
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- T lymphocyte acute lymphoblastic leukemia (T-ALL) is a heterogeneous disease affecting T cells at multiple stages of their development and is characterized by frequent genomic alterations. The transcription factor LEF1 is inactivated through mutation in a subset of T-ALL cases but elevated LEF1 expression and activating mutations have also been identified in this disease. Here we show, in a murine model of T-ALL arising due to E2a inactivation, that the developmental timing of Lef1 mutation impacts its ability to function as a cooperative tumor suppressor or oncogene. T cell transformation in the presence of LEF1 allows leukemic cells to become addicted to its presence. In contrast, deletion prior to transformation both accelerates leukemogenesis and results in leukemic cells with altered expression of genes controlling receptor-signaling pathways. Our data demonstrate that the developmental timing of Lef1 mutations impact its apparent oncogenic or tumor suppressive characteristics and demonstrate the utility of mouse models for understanding the cooperation and consequence of mutational order in leukemogenesis.
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| 2. |
- Kitson, Alison L., et al.
(författare)
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‘No more heroes’ : The ILC Oxford Statement on fundamental care in times of crises
- 2023
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Ingår i: Journal of Advanced Nursing. - : John Wiley & Sons. - 0309-2402 .- 1365-2648. ; 79:3, s. 922-932
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Forskningsöversikt (refereegranskat)abstract
- AimTo outline the International Learning Collaborative (ILC) Oxford Statement, explicating our commitment to ensuring health and care systems are equipped to meet patients' fundamental care needs during times of unprecedented crisis. Design/MethodDiscussion paper. The content was developed via a co-design process with participants during the ILC's international conference. Key ArgumentsWe, the ILC, outline what we do and do not want to see within our health and care systems when faced with the challenges of caring for patients during global pandemics and other crises. Specifically, we want fundamental care delivery to be seen as the minimum standard rather than the exception across our health and care systems. We want nursing leaders to call out and stand up for the importance of building fundamental care into systems, processes and funding priorities. We do not want to see the voices of nursing leaders quashed or minimized in favour of other agendas. In turn, what we want to see is greater recognition of fundamental care work and greater respect for the people who do it. We expect nurses to have a 'seat at the table' where the key health and care decisions that impact patients and staff are made. ConclusionTo achieve our goals we must (1) ensure that fundamental care is embedded in all health and care systems, at all levels; (2) build on and strengthen the leadership skills of the nursing workforce by clearly advocating for person-centred fundamental care; (3) co-design systems that care for and support our staff's well-being and which foster collective resilience rather than overly rely on individual resilience; (4) improve the science and methodologies around reporting and measuring fundamental care to show the positive impact of this care delivery and (5) leverage the COVID pandemic crisis as an opportunity for transformational change in fundamental care delivery.
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| 3. |
- Kitson, Alison, et al.
(författare)
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Speaking Up for Fundamental Care : the ILC Aalborg Statement
- 2019
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Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 9:12
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The International Learning Collaborative (ILC) is an organisation dedicated to understanding why fundamental care, the care required by all patients regardless of clinical condition, fails to be provided in healthcare systems globally. At its 11th annual meeting in 2019, nursing leaders from 11 countries, together with patient representatives, confirmed that patients' fundamental care needs are still being ignored and nurses are still afraid to 'speak up' when these care failures occur. While the ILC's efforts over the past decade have led to increased recognition of the importance of fundamental care, it is not enough. To generate practical, sustainable solutions, we need to substantially rethink fundamental care and its contribution to patient outcomes and experiences, staff well-being, safety and quality, and the economic viability of healthcare systems.KEY ARGUMENTS: We present five propositions for radically transforming fundamental care delivery:Value: fundamental care must be foundational to all caring activities, systems and institutionsTalk: fundamental care must be explicitly articulated in all caring activities, systems and institutions.Do: fundamental care must be explicitly actioned and evaluated in all caring activities, systems and institutions.Own: fundamental care must be owned by each individual who delivers care, works in a system that is responsible for care or works in an institution whose mission is to deliver care.RESEARCH: fundamental care must undergo systematic and high-quality investigations to generate the evidence needed to inform care practices and shape health systems and education curricula.CONCLUSION: For radical transformation within health systems globally, we must move beyond nursing and ensure all members of the healthcare team-educators, students, consumers, clinicians, leaders, researchers, policy-makers and politicians-value, talk, do, own and research fundamental care. It is only through coordinated, collaborative effort that we will, and must, achieve real change.
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| 4. |
- Xu, Wei, et al.
(författare)
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E2A transcription factors limit expression of Gata3 to facilitate T lymphocyte lineage commitment
- 2013
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 121:9, s. 1534-1542
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Tidskriftsartikel (refereegranskat)abstract
- The E2A transcription factors promote the development of thymus-seeding cells, but it remains unknown whether these proteins play a role in T lymphocyte lineage specification or commitment. Here, we showed that E2A proteins were required to promote T-lymphocyte commitment from DN2 thymocytes and to extinguish their potential for alternative fates. E2A proteins functioned in DN2 cells to limit expression of Gata3, which encodes an essential T-lymphocyte transcription factor whose ectopic expression can arrest T-cell differentiation. Genetic, or small interfering RNA-mediated, reduction of Gata3 rescued T-cell differentiation in the absence of E2A and restricted the development of alternative lineages by limiting the expanded self-renewal potential in E2A(-/-) DN2 cells. Our data support a novel paradigm in lymphocyte lineage commitment in which the E2A proteins are necessary to limit the expression of an essential lineage specification and commitment factor to restrain self-renewal and to prevent an arrest in differentiation.
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