BCL-3 expression promotes colorectal tumorigenesis through activation of AKT signalling

Objective Colorectal cancer remains the fourth most common cause of cancer-related mortality worldwide. Here we investigate the role of nuclear factor-?B (NF-?B) co-factor B-cell CLL/lymphoma 3 (BCL-3) in promoting colorectal tumour cell survival. Design Immunohistochemistry was carried out on 47 tumour samples and normal tissue from resection margins. The role of BCL-3/NF-?B complexes on cell growth was studied in vivo and in vitro using an siRNA approach and exogenous BCL-3 expression in colorectal adenoma and carcinoma cells. The question whether BCL-3 activated the AKT/protein kinase B (PKB) pathway in colorectal tumour cells was addressed by western blotting and confocal microscopy, and the ability of 5- aminosalicylic acid (5-ASA) to suppress BCL-3 expression was also investigated. Results We report increased BCL-3 expression in human colorectal cancers and demonstrate that BCL-3 expression promotes tumour cell survival in vitro and tumour growth in mouse xenografts in vivo, dependent on interaction with NF-?B p50 or p52 homodimers. We show that BCL-3 promotes cell survival under conditions relevant to the tumour microenvironment, protecting both colorectal adenoma and carcinoma cells from apoptosis via activation of the AKT survival pathway: AKT activation is mediated via both PI3K and mammalian target of rapamycin (mTOR) pathways, leading to phosphorylation of downstream targets GSK- 3 and FoxO1/3a. Treatment with 5-ASA suppressed BCL-3 expression in colorectal cancer cells. Conclusions Our study helps to unravel the mechanism by which BCL-3 is linked to poor prognosis in colorectal cancer; we suggest that targeting BCL-3 activity represents an exciting therapeutic opportunity potentially increasing the sensitivity of tumour cells to conventional therapy

CAMAU Project: Research Report (April 2018)

‘Learning about Progression’ is a suite of research-based resources designed to provide evidence to support the building of learning progression frameworks in Wales. ‘Learning about Progression’ seeks to deepen our understanding of current thinking about progression and to explore different purposes that progression frameworks can serve to improve children and young people’s learning. These resources include consideration of how this evidence relates to current developments in Wales and derives a series of principles to serve as touchstones to make sure that, as practices begin to develop, they stay true to the original aspirations of A Curriculum for Wales – A Curriculum for Life. It also derives, from the review of evidence, a number of fundamental questions for all those involved in the development of progression frameworks to engage

CAMAU Project: Research Report (April 2018)

‘Learning about Progression’ is a suite of research-based resources designed to provide evidence to support the building of learning progression frameworks in Wales. ‘Learning about Progression’ seeks to deepen our understanding of current thinking about progression and to explore different purposes that progression frameworks can serve to improve children and young people’s learning. These resources include consideration of how this evidence relates to current developments in Wales and derives a series of principles to serve as touchstones to make sure that, as practices begin to develop, they stay true to the original aspirations of A Curriculum for Wales – A Curriculum for Life. It also derives, from the review of evidence, a number of fundamental questions for all those involved in the development of progression frameworks to engage

Writing in Britain and Ireland, c. 400 to c. 800

No abstract available

The Zinc Finger Protein A20 Inhibits TNF-induced NF-κB–dependent Gene Expression by Interfering with an RIP- or TRAF2-mediated Transactivation Signal and Directly Binds to a Novel NF-κB–inhibiting Protein ABIN

The zinc finger protein A20 is a tumor necrosis factor (TNF)– and interleukin 1 (IL-1)-inducible protein that negatively regulates nuclear factor-kappa B (NF-κB)–dependent gene expression. However, the molecular mechanism by which A20 exerts this effect is still unclear. We show that A20 does not inhibit TNF- induced nuclear translocation and DNA binding of NF-κB, although it completely prevents the TNF- induced activation of an NF-κB–dependent reporter gene, as well as TNF-induced IL-6 and granulocyte macrophage–colony stimulating factor gene expression. Moreover, NF-κB activation induced by overexpression of the TNF receptor–associated proteins TNF receptor–associated death domain protein (TRADD), receptor interacting protein (RIP), and TNF recep- tor–associated factor 2 (TRAF2) was also inhibited by expression of A20, whereas NF-κB activation induced by overexpression of NF-κB–inducing kinase (NIK) or the human T cell leukemia virus type 1 (HTLV-1) Tax was unaffected. These results demonstrate that A20 inhibits NF-κB–dependent gene expression by interfering with a novel TNF-induced and RIP- or TRAF2-mediated pathway that is different from the NIK–IκB kinase pathway and that is specifically involved in the transactivation of NF-κB. Via yeast two-hybrid screening, we found that A20 binds to a novel protein, ABIN, which mimics the NF-κB inhibiting effects of A20 upon overexpression, suggesting that the effect of A20 is mediated by its interaction with this NF-κB inhibiting protein, ABIN

Field Ionization of Neutral Litium Vapor Using a 28.5 GeV Electron Beam

The E164/E164X plasma wakefield experiment studies beam-plasma interactions at the Stanford Linear Acceleration Center (SLAC). Due to SLAC's recent ability to variably compress bunches longitudinally from 650 {micro}m down to 20 {micro}m, the incoming beam is sufficiently dense to field ionize the neutral lithium (Li) vapor. The field ionization effects are characterized by the beams energy loss through the Li vapor column. Experiment results are presented

Positron Production by X Rays Emitted By Betatron Motion in a Plasma Wiggler

Positrons in the energy range of 3-30 MeV, produced by x rays emitted by betatron motion in a plasma wiggler of 28.5 GeV electrons from the SLAC accelerator, have been measured. The extremely high-strength plasma wiggler is an ion column induced by the electron beam as it propagates through and ionizes dense lithium vapor. X rays in the range of 1-50 MeV in a forward cone angle of 0.1 mrad collide with a 1.7 mm thick tungsten target to produce electron-positron pairs. The positron spectra are found to be strongly influenced by the plasma density and length as well as the electron bunch length. By characterizing the beam propagation in the ion column these influences are quantified and result in excellent agreement between the measured and calculated positron spectra

Field Ionization using a 28.5 GeV Electron Beam

The E164/E164X plasma wakefield experiment studies beam-plasma interactions at the Stanford Linear Acceleration Center (SLAC). Due to SLAC's recent ability to variably compress bunches longitudinally from 650 {micro}m down to 20 {micro}m, the incoming beam is sufficiently dense to field ionize the neutral lithium (Li) vapor. The field ionization effects are characterized by the beams energy loss through the Li vapor column. Experiment results are presented

Conceptualising fields of action for sustainable intensification A systematic literature review and application to regional case studies

[EN] After two decades of research on sustainable intensification (SI), namely securing food production on less environmental cost, heterogeneous understandings and perspectives prevail in a broad and partly fragmented scientific literature. Structuring and consolidating contributions to provide practice-oriented guidelines are lacking. The objectives of this study are to (1) comprehensively explore the academic SI literature, (2) propose an implementation-oriented conceptual framework, and (3) demonstrate its applicability for region-specific problem settings. In a systematic literature review of 349 papers covering the international literature of 20 years of SI research, we identified SI practices and analysed temporal, spatial and disciplinary trends and foci. Based on key SI practices, a conceptual framework was developed differentiating four fields of action from farm to regional and landscape scale and from land use to structural optimisation. Its applicability to derive region specific SI solutions was successfully tested through stakeholder processes in four European case studies. Disciplinary boundaries and the separation of the temporal and spatial strands in the literature prevent a holistic address of SI. This leads to the dominance of research describing SI practices in isolation, mainly on the farm scale. Coordinated actions on the regional scale and the coupling of multiple practices are comparatively un-derrepresented. Results from the case studies demonstrate that implementation is extremely context-sensitive and thus crucially depends on the situational knowledge of farmers and stakeholders. Although, there is no 'one size fits all' solution, practitioners in all regions identified the need for integrated solutions and common action to implement suitable SI strategies at the regional landscape level and in local ecosystems.This research was financially supported by the European Commission under grant agreement 652615 and conducted in the context of the ERA-Net FACCE SURPLUS project VITAL, with the national funders NWO (Netherlands), BMBF (Germany), INIA (Spain), ANR (France).Weltin, M.; Zasada, I.; Piorr, A.; Debolini, M.; Geniaux, G.; Moreno-Pérez, OM.; Scherer, L.... (2018). Conceptualising fields of action for sustainable intensification A systematic literature review and application to regional case studies. Agriculture Ecosystems & Environment. 257:68-80. https://doi.org/10.1016/j.agee.2018.01.023S688025