Notch/Delta signaling constrains reengineering of pro-T cells by PU.1

PU.1 is essential for early stages of mouse T cell development but antagonizes it if expressed constitutively. Two separable mechanisms are involved: attenuation and diversion. Dysregulated PU.1 expression inhibits pro-T cell survival, proliferation, and passage through β-selection by blocking essential T cell transcription factors, signaling molecules, and Rag gene expression, which expression of a rearranged T cell antigen receptor transgene cannot rescue. However, Bcl2 transgenic cells are protected from this attenuation and may even undergo β-selection, as shown by PU.1 transduction of defined subsets of Bcl2 transgenic fetal thymocytes with differentiation in OP9-DL1 and OP9 control cultures. The outcome of PU.1 expression in these cells depends on Notch/Delta signaling. PU.1 can efficiently divert thymocytes toward a myeloid-like state with multigene regulatory changes, but Notch/Delta signaling vetoes diversion. Gene expression analysis distinguishes sets of critical T lineage regulatory genes with different combinatorial responses to PU.1 and Notch/Delta signals, suggesting particular importance for inhibition of E proteins, Myb, and/or Gfi1 (growth factor independence 1) in diversion. However, Notch signaling only protects against diversion of cells that have undergone T lineage specification after Thy-1 and CD25 up-regulation. The results imply that in T cell precursors, Notch/Delta signaling normally acts to modulate and channel PU.1 transcriptional activities during the stages from T lineage specification until commitment

World of Viruses: the Frozen Horror

https://digitalcommons.unmc.edu/coph_books/1000/thumbnail.jp

Biodiversity 2020: climate change evaluation report

In 2011, the government published Biodiversity 2020: A strategy for England’s wildlife and ecosystem services [1]. This strategy for England builds on the 2011 Natural Environment White Paper - NEWP [2] and provides a comprehensive picture of how we are implementing our international and EU commitments. It sets out the strategic direction for biodiversity policy between 2011-2020 on land (including rivers and lakes) and at sea, and forms part of the UK’s commitments under the ‘the Aichi targets’ agreed in 2010 under the United Nations Convention of Biological Diversity’s Strategic Plan for Biodiversity 2011-2020 [3]. Defra is committed to evaluating the Biodiversity 2020 strategy and has a public commitment to assess climate change adaptation measures. This document sets out the information on assessing how action under Biodiversity 2020 has helped our wildlife and ecosystems to adapt to climate change. Biodiversity 2020 aims to halt the loss of biodiversity and restore functioning ecosystems for wildlife and for people. The outcomes and actions in Biodiversity 2020, although wider in scope, aimed to increase resilience of our wildlife and ecosystems in the face of a changing climate. In order to inform the assessment, we have defined which of the measurable outputs under Biodiversity 2020 contribute to resilience. Biodiversity 2020 included plans to develop and publish a dedicated set of indicators to assess progress towards the delivery of the strategy. The latest list (at the time of writing), published in 2017, contains 24 biodiversity indicators [4] that would help inform progress towards achieving specific outcomes, they are also highly relevant to the outputs (detailed below) that form the basis for this evaluation. The Adaptation Sub-Committee’s 2017 UK Climate Change Risk Assessment Evidence Report [5] sets out the priority climate change risks and opportunities for the UK. The ASC also produced a review of progress in the National Adaptation Programme - “Progress in preparing for climate change” [6], which highlights adaptation priorities and progress being made towards achieving them. The UK Government’s response to the ASC [7] review includes a set of recommendations, of which Recommendation 6 states that “Action should be taken to enhance the condition of priority habitats and the abundance and range of priority species”. The recommendation further iterated that “This action should maintain or extend the level of ambition that was included in Biodiversity 2020” and that “An evaluation should be undertaken of Biodiversity 2020 including the extent to which goals have been met and of the implications for resilience to climate change.” To this, end an evaluation process has been put in place to define: a. What worked and why? Which actions or activities have had the greatest benefit in terms of delivering the desired outcomes? And, conversely, what prevented progress? b. Where are the opportunities? What are the financial, political, scientific and social opportunities for furthering the desired outcomes in the future? These objectives underpin the evaluation process for actions to date, and will also inform future actions and the iteration of a new nature strategy for England

The Grizzly, September 28, 1993

The Quilt\u27s Arrival: To Remember • Dawleys Appointed Biology Co-Chairs • Russian President Yeltsin Dissolves Parliament • Model UN Seeks New Delegation • Billy Joel Rocks Philly • Javapalooza • Big Al Day Exposed • Fitness Forum • Freshman Primer • Letter: Faculty Members Point Out Error • Tutorial Program Strengthens Ursinus • Ursinus Perceived as Anti-Gay • UC Training Staff Saves the Day • Bear Pack Way Ahead Again • Football Holds Off Western Maryland • Scooter\u27s Dayhttps://digitalcommons.ursinus.edu/grizzlynews/1319/thumbnail.jp

The Grizzly, October 5, 1993

Girls\u27 Pledging Returns Full-Force! • India Shattered by Earthquakes • Acting PA Governor Will Hold TV Town Meeting at Ursinus • Freshman to Compete in Karate\u27s World Cup • Henry Moore Exhibit Opens Today • Charles Fambrough Quintet to Play Ursinus • Editorial: Pledging; Wellness Center • Intramurals Begin: Sign Up! • Bears Crush Garnet Into Pebbleshttps://digitalcommons.ursinus.edu/grizzlynews/1320/thumbnail.jp

The Grizzly, October 26, 1993

Colvin, Reynolds to Serve on Captains\u27 Council • Verdict Returned in Reginald Denny Trial • Ursinus Loses Friend and Supporter • Student Apathy Strikes Again • Ursinus Students to Perform in State Choral Festival • Gaijin-Eyes Exhibit to Open • Literary Society • Self-Realization in the Big Apple: Wiggly Blocks and The Piano • Bears Win Homecoming • Phillies Lose World Serieshttps://digitalcommons.ursinus.edu/grizzlynews/1322/thumbnail.jp

Developmental and Molecular Characterization of Emerging β- and γδ-Selected Pre-T Cells in the Adult Mouse Thymus

The first checkpoint in T cell development, β selection, has remained incompletely characterized for lack of specific surface markers. We show that CD27 is upregulated in DN3 thymocytes initiating β selection, concomitant with intracellular TCR-β expression. Clonal analysis determined that CD27^(high) DN3 cells generate CD4^+CD8^+ progeny with more than 90% efficiency, faster and more efficiently than the CD27^(low) majority. CD27 upregulation also occurs in γδ-selected DN3 thymocytes in TCR-β−/− mice and in IL2-GFP transgenic reporter mice where GFP marks the earliest emerging TCR-γδ cells from DN3 thymocytes. With CD27 to distinguish pre- and postselection DN3 cells, a detailed gene expression analysis defined regulatory changes associated with checkpoint arrest, with β selection, and with γδ selection. γδ selection induces higher CD5, Egr, and Runx3 expression as compared to β selection, but it triggers less proliferation. Our results also reveal differences in Notch/Delta dependence at the earliest stages of divergence between developing αβ and γδ T-lineage cells

Lime stabilisation for earthworks: a UK perspective

Lime stabilisation is a versatile technique applied during earthworks operations. Modern soil recycling units are much more efficient at pulverising fill material and intermixing the added binder/water than machinery available 20 years ago. While supplier innovation adds flexibility to the site working method, specifications have not been sufficiently updated to permit optimal application. This review paper details the physico-chemical changes instigated through the lime-clay soil reaction, updating previous reviews. It aims to assist scientific debate, current practitioners and future specification changes. For example, the application of the minimum 24 h mellowing periods (mandatory to UK specifications) with high reactivity, quicklime powders is concluded to cause increased air voids in the compacted fill. Increased air voids are associated with reduced long-term strength and potential volume change from water ingress, which is of particular concern for sulfate swelling. Shorter mellowing periods and/or use of hydrated lime may lesson this issue; however, a 'one size fits all' approach is discouraged in preference to site-specific methodologies refined to suit the fill material and project requirements. The discussion also summarises working methods which may lower the risk of sulfate swell and defines areas requiring further practical research