44 research outputs found

    Increased Expression of PcG Protein YY1 Negatively Regulates B Cell Development while Allowing Accumulation of Myeloid Cells and LT-HSC Cells

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    Ying Yang 1 (YY1) is a multifunctional Polycomb Group (PcG) transcription factor that binds to multiple enhancer binding sites in the immunoglobulin (Ig) loci and plays vital roles in early B cell development. PcG proteins have important functions in hematopoietic stem cell renewal and YY1 is the only mammalian PcG protein with DNA binding specificity. Conditional knock-out of YY1 in the mouse B cell lineage results in arrest at the pro-B cell stage, and dosage effects have been observed at various YY1 expression levels. To investigate the impact of elevated YY1 expression on hematopoetic development, we utilized a mouse in vivo bone marrow reconstitution system. We found that mouse bone marrow cells expressing elevated levels of YY1 exhibited a selective disadvantage as they progressed from hematopoietic stem/progenitor cells to pro-B, pre-B, immature B and re-circulating B cell stages, but no disadvantage of YY1 over-expression was observed in myeloid lineage cells. Furthermore, mouse bone marrow cells expressing elevated levels of YY1 displayed enrichment for cells with surface markers characteristic of long-term hematopoietic stem cells (HSC). YY1 expression induced apoptosis in mouse B cell lines in vitro, and resulted in down-regulated expression of anti-apoptotic genes Bcl-xl and NFΞΊB2, while no impact was observed in a mouse myeloid line. B cell apoptosis and LT-HSC enrichment induced by YY1 suggest that novel strategies to induce YY1 expression could have beneficial effects in the treatment of B lineage malignancies while preserving normal HSCs

    Ten practical realities for institutional animal care and use committees when evaluating protocols dealing with fish in the field

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    Institutional Animal Care and Use Committee’s (IACUCs) serve an important role in ensuring that ethical practices are used by researchers working with vertebrate taxa including fish. With a growing number of researchers working on fish in the field and expanding mandates of IACUCs to regulate field work, there is potential for interactions between aquatic biologists and IACUCs to result in unexpected challenges and misunderstandings. Here we raise a number of issues often encountered by researchers and suggest that they should be taken into consideration by IACUCs when dealing with projects that entail the examination of fish in their natural environment or other field settings. We present these perspectives as ten practical realities along with their implications for establishing IACUC protocols. The ten realities are: (1) fish are diverse; (2) scientific collection permit regulations may conflict with IACUC policies; (3) stakeholder credibility and engagement may constrain what is possible; (4) more (sample size) is sometimes better; (5) anesthesia is not always needed or possible; (6) drugs such as analgesics and antibiotics should be prescribed with care; (7) field work is inherently dynamic; (8) wild fish are wild; (9) individuals are different, and (10) fish capture, handling, and retention are often constrained by logistics. These realities do not imply ignorance on the part of IACUCs, but simply different training and experiences that make it difficult for one to understand what happens outside of the lab where fish are captured and not ordered/purchased/reared, where there are engaged stakeholders, and where there is immense diversity (in size, morphology, behaviour, life-history, physiological tolerances) such that development of rigid protocols or extrapolation from one species (or life-stage, sex, size class, etc.) to another is difficult. We recognize that underlying these issues is a need for greater collaboration between IACUC members (including veterinary professionals) and field researchers which would provide more reasoned, rational and useful guidance to improve or maintain the welfare status of fishes used in field research while enabling researchers to pursue fundamental and applied questions related to the biology of fish in the field. As such, we hope that these considerations will be widely shared with the IACUCs of concerned researchers

    Hyponatremia in the intensive care unit: How to avoid a Zugzwang situation?

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    The value of an allotment group for refugees

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    Introduction: Refugees experience a number of difficulties when settling in the United Kingdom and may be faced with occupational injustice due to their restricted occupational engagement. This study explores the value of an allotment group for refugees of working age, aiming to explore the role of horticulture and the social environment on health, wellbeing and social inclusion. Method: This was an exploratory study using qualitative methodology based on ethnographic principles. Data collection included observation of the group, semi-structured interviews with five participants, with four of these participants also taking part in photo-elicitation interviews. Data analysis involved using a 'framework' approach to produce three themes and associated sub-themes. Findings: Analysis identified firstly gardening as a meaningful activity; secondly, the importance of the social environment and, lastly, the value of occupational engagement for refugees. Further theoretical analysis led to the conclusion that these themes linked to the dimensions of occupation: doing, being, belonging and becoming. Conclusion: The findings identify how occupational engagement can have a positive impact on the health and wellbeing of refugees, specifically with the use of social and therapeutic horticulture
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