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Abstract Background Dysregulated Notch signalling is believed to play an important role in the development and maintenance of T cell leukaemia. At a cellular level, Notch signalling promotes proliferation and inhibits apoptosis of T cell acute lymphoblastic leukaemia (T-ALL) cells. In this study we aimed to identify novel transcriptional targets of Notch signalling in the T-ALL cell line, Jurkat. Results RNA was prepared from Jurkat cells retrovirally transduced with an empty vector (GFP-alone) or vectors containing constitutively active forms of Notch (N1ΔE or N3ΔE), and used for Affymetrix microarray analysis. A subset of genes found to be regulated by Notch was chosen for real-time PCR validation and in some cases, validation at the protein level, using several Notch-transduced T-ALL and non-T-ALL leukaemic cell lines. As expected, several known transcriptional target of Notch, such as HES1 and Deltex, were found to be overexpressed in Notch-transduced cells, however, many novel transcriptional targets of Notch signalling were identified using this approach. These included the T cell costimulatory molecule CD28, the anti-apoptotic protein GIMAP5, and inhibitor of DNA binding 1 (1D1). Conclusion The identification of such downstream Notch target genes provides insights into the mechanisms of Notch function in T cell leukaemia, and may help identify novel therapeutic targets in this disease.

This study aims to capture the online experiences of young people when interacting with algorithm mediated systems and their impact on their well-being. We draw on qualitative (focus groups) and quantitative (survey) data from a total of 260 young people to bring their opinions to the forefront while eliciting discussions. The results of the study revealed the young people's positive as well as negative experiences of using online platforms. Benefits such as convenience, entertainment and personalised search results were identified. However, the data also reveals participants' concerns for their privacy, safety and trust when online, which can have a significant impact on their well-being. We conclude by recommending that online platforms acknowledge and enact on their responsibility to protect the privacy of their young users, recognising the significant developmental milestones that this group experience during these early years, and the impact that algorithm mediated systems may have on them. We argue that governments need to incorporate policies that require technologists and others to embed the safeguarding of users' well-being within the core of the design of Internet products and services to improve the user experiences and psychological well-being of all, but especially those of children and young people. [ABSTRACT FROM AUTHOR]

Objective Notch signalling has been implicated in haematopoietic stem cell self-renewal. Although several studies have tested the effect of activating or inhibiting the Notch signalling pathway in stem cells, no study has yet determined the functional differences associated with expressing Notch1. The aims of this study were to characterise the expression of human cell-surface Notch1 in cord blood ( CB) CD34+ cells and to study the function of Notch in CD34+ cells in vitro. Methods A monoclonal antibody against the extracellular domain of Notch1 was developed, and Notch1 expression in CB CD34+ cells was assessed by flow cytometry. CB CD34+ cells were sorted on the basis of their Notch1 expression and cultured in serum-free media. Single sorted CD34+ CD38− Notch1+/− cells were cultured for 8 wks on murine stroma monolayers and assayed for stem cell activity and lineage potential using a cobblestone area-forming cell ( CAFC) assay. Results Cell-surface Notch1 expression was characterised in various primitive CD34+ cell compartments including a small subpopulation of CD34+ CD38− cells. We found the CD34+ CD38− Notch1+ population to be enriched for stem cell activity. Moreover, CD34+ CD38− Notch1+, but not Notch1− cells, demonstrated multilineage potential. Conclusions These data show that Notch1 is expressed on a functionally distinct subpopulation of CD34+ cells that is highly enriched for stem cell activity and multilineage potential and could suggest that Notch1 could be used as a novel stem cell marker. [ABSTRACT FROM AUTHOR]

Background: Digital contact tracing is employed to monitor and manage the spread of Covid-19. However, to be effective the system must be adopted by a substantial proportion of the population. Studies of (mostly hypothetical) contact tracing apps show generally high acceptance, but little is known about the drivers and barriers to adoption of deployed systems.Objective: The aim of this study is to investigate adoption and attitudes towards the NHS Covid-19 smartphone app, the digital contact tracing solution in the UK.Methods: An online survey based on the technology acceptance model (TAM2) with the added factor of trust was carried out with a representative sample of the UK population. Statistical analysis shows adoption rates, attitudes towards and trust in the app, compliance with self-isolation advice, and highlights differences for vulnerable populations (older adults over 65 years of age and members of Black, Asian, and Minority Ethnic (BAME) communities).Results: Around half of the 1,001 (50.9%, 95% CI:47.8-54.0%) respondents had downloaded and kept the app, but more than a third (35.8%, CI:32.8-38.8%) either did not intend to download it or had deleted it. Significantly more BAME respondents had deleted the app (13.9%, CI :11.8-16.0%, vs 7.4%, CI: 5.8-9.0%), and significantly more older adults over 65 years old did not intend to download it (34.6%, CI: 31.7-37.5% vs 25.2% CI: 22.5-27.9%). Reasons for uptake were broadly to help the NHS and other people, especially among older adults, although significantly fewer BAME agreed that they did so to help the NHS. Reported compliance with received notifications to self-isolate was high, but significantly lower than reported intended compliance without received notifications. Only a fifth (19.5%, CI: 17.0-22.0%) understood that the decision to send self-isolation notifications is automated by the app. There were a range of significantly more negative views among BAME participants, including lower trust in the NHS, whilst older adults were often significantly more positive. Respondents without the app reported significantly lower trust and more negative views towards the app and were less likely to report they understood how the app works.Conclusions: Whilst compliance of the ~50% who have the app is fairly high, there are issues surrounding trust and understanding that hinder adoption and therefore the effectiveness of digital contact tracing, particularly amongst BAME communities. The study highlights that more needs to be done to improve adoption among groups who are more vulnerable to the effects of the virus to enhance uptake and acceptance of contact tracing apps.Clinicaltrial: [ABSTRACT FROM AUTHOR]

Objective: Notch signalling has been implicated in haematopoietic stem cell self-renewal. Although several studies have tested the effect of activating or inhibiting the Notch signalling pathway in stem cells, no study has yet determined the functional differences associated with expressing Notch1. The aims of this study were to characterise the expression of human cell-surface Notch1 in cord blood (CB) CD34(+) cells and to study the function of Notch in CD34(+) cells in vitro., Methods: A monoclonal antibody against the extracellular domain of Notch1 was developed, and Notch1 expression in CB CD34(+) cells was assessed by flow cytometry. CB CD34(+) cells were sorted on the basis of their Notch1 expression and cultured in serum-free media. Single sorted CD34(+) CD38(-) Notch1(+) /(-) cells were cultured for 8 wks on murine stroma monolayers and assayed for stem cell activity and lineage potential using a cobblestone area-forming cell (CAFC) assay., Results: Cell-surface Notch1 expression was characterised in various primitive CD34(+) cell compartments including a small subpopulation of CD34(+) CD38(-) cells. We found the CD34(+) CD38(-) Notch1(+) population to be enriched for stem cell activity. Moreover, CD34(+) CD38(-) Notch1(+) , but not Notch1(-) cells, demonstrated multilineage potential., Conclusions: These data show that Notch1 is expressed on a functionally distinct subpopulation of CD34(+) cells that is highly enriched for stem cell activity and multilineage potential and could suggest that Notch1 could be used as a novel stem cell marker., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)