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    The Pseudokinase TRIB3 Negatively Regulates the HER2 Receptor Pathway and Is a Biomarker of Good Prognosis in Luminal Breast Cancer

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    From MDPI via Jisc Publications RouterHistory: accepted 2021-10-19, pub-electronic 2021-10-22Publication status: PublishedFunder: Instituto de Salud Carlos III; Grant(s): PI18/00442Funder: European Commission; Grant(s): ITN-308 2016 721532Funder: Breast Cancer Now; Grant(s): 2012NovSP033Funder: Ministry of Economy, Industry and Competitiveness; Grant(s): RTI2018-094130-B-100Background: Tribbles pseudokinase 3 (TRIB3) has been proposed to both promote and restrict cancer generation and progression. However, the precise mechanisms that determine this dual role of TRIB3 in cancer remain to be understood. In this study we aimed to investigate the role of TRIB3 in luminal breast cancer, the most frequent subtype of this malignancy. Methods: We genetically manipulated TRIB3 expression in a panel of luminal breast cancer cell lines and analyzed its impact on cell proliferation, and the phosphorylation, levels, or subcellular localization of TRIB3 and other protein regulators of key signaling pathways in luminal breast cancer. We also analyzed TRIB3 protein expression in samples from luminal breast cancer patients and performed bioinformatic analyses in public datasets. Results: TRIB3 enhanced the proliferation and AKT phosphorylation in luminal A (HER2-) but decreased them in luminal B (HER2+) breast cancer cell lines. TRIB3 negatively regulated the stability of HER2 in luminal B breast cancer cell lines. TRIB3 expression was associated with increased disease-free survival and a better response to therapy in luminal breast cancer patients. Conclusions: Our findings support the exploration of TRIB3 as a potential biomarker and therapeutic target in luminal breast cancer

    Sex and age-specific survival and life expectancy in a free ranging population of Indri indri (Gmelin, 1788).

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    This is an Accepted Manuscript of an article published by Taylor & Francis in European Zoological Journal on 22 July 2021, available online: https://doi.org/10.1080/24750263.2021.1947398The critically endangered indri (Indri indri) is the largest extant lemur species and its population size is projected to decline over the next three generations due to habitat loss, hunting and climate change. Accurate information on the demographic parameters driving the population dynamics of indri is urgently needed to help decision-making regarding the conservation of this iconic species. We monitored and followed the life histories of 68 individually recognizable indris in 10 family groups in the Maromizaha New Protected Area (Madagascar) for 12 years. We estimated age and sex-specific survival trajectories using a Bayesian hierarchical survival model and found that the survival curves for male and female indris show a similar pattern, consistent with what found typically in primates; i.e., a high infant mortality rate which declines with age in the juvenile phase and increases again for adults. Also, life expectancies at 2 years of age (e2), were found to be similar between the sexes (e2 females = 7.8 years; e2 males = 7.5 years). We suggest that the lack of strong differences in the survival patterns for male and female indris are related to the strictly monogamous mating system and the lack of sexual dimorphism in this species. Our study provides, for the first time, robust estimates for demographic parameters of indris and one of the very few datasets on survival trajectories available for primates

    The Mistress turned Medicant

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    A foundational piece explaining the principles and interests of the National Plant Collection of Mentha and it's cultural positionality in relation to education, folklore, biodiversity, sustainability, and wellbeing

    Ethically sensitive research with ‘children’ and ‘adults’ in custody

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    This chapter draws on data from young men interviewed on two occasions; first as ‘children’ aged 17 years within juvenile Young Offenders’ Institutions (YOIs); and then again as ‘adults’ aged 18 years within young adult/adult prisons about their experiences of transitions. Ethical reviews typically reflect age-determined constructions of child/adult status and those aged under 18 years are deemed to be more ‘vulnerable’, thus attracting more scrutiny from research ethics committees (Economic and Social Research Council [ESRC] 2020). This concern heightens the methodological difficulties of prison research, as incarceration renders children ‘doubly vulnerable’ (Jacobson and Talbot 2017). Such institutions may be obstructive and access must be obtained from a series of gatekeepers. Negotiating the balance between participants’ rights and their best interests (Heptinstall 2000, Thomas and O’Kane 1998), along with gatekeepers’ priorities can be challenging. This chapter outlines how tricky ethical tensions were balanced with participants’ best interests in line with the United Nations Convention on the Rights of the Child (CRC) (UN 1989). Despite the difficulties encountered, the researcher (JP) took the view that there would be ‘ethical implication[s] of NOT conducting the research’ (Girling 2017, p. 38). The chapter offers recommendations for how researchers might conduct ethically sensitive research with similar cohorts of young people

    The supervisor conundrum

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    Behavioural Indicators of Intra- and Inter-Specific Competition: Sheep Co-Grazing with Guanaco in the Patagonian Steppe

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    In extensive livestock production, high densities may inhibit regulation processes, main- taining high levels of intraspecific competition over time. During competition, individuals typically modify their behaviours, particularly feeding and bite rates, which can therefore be used as indicators of competition. Over eight consecutive seasons, we investigated if variation in herd density, food availability, and the presence of a potential competitor, the guanaco (Lama guanicoe), was related with behavioural changes in domestic sheep in Chilean Patagonia. Focal sampling, instantaneous scan sampling, measures of bite and movement rates were used to quantify behavioural changes in domestic sheep. We found that food availability increased time spent feeding, while herd density was associated with an increase in vigilant behaviour and a decrease in bite rate, but only when food availability was low. Guanaco presence appeared to have no impact on sheep behaviour. Our results suggest that the observed behavioural changes in domestic sheep are more likely due to intraspecific competition rather than interspecific competition. Consideration of intraspecific competition where guanaco and sheep co-graze on pastures could allow management strategies to focus on herd density, according to rangeland carrying capacity

    Volatile Liquid Detection by Terahertz Technologies

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    The prospect of being able to move through security without the inconvenience of separating liquids from bags is an exciting one for passengers, and there are important operational benefits for airports as well. Here, two terahertz (THz) systems, 100 GHz sub-THz line scanner and attenuation total reflection-based THz time domain spectroscopy (TDS), have been used to demonstrate the capability of identifying different liquid samples. Liquid samples’ THz complex permittivities are measured and their differences have contributed to the variation of 100 GHz 2D images of volatile liquids with different volumes inside of cannister bottles. The acquired attenuation images at 100 GHz can easily be used to distinguish highly absorbed liquids (Water, Ethanol, Fuel Treatment Chemicals) and low loss liquids (Petrol, Diesel, Kerosene and Universal Bottle Cleaner). The results give a promising feasibility for mm-wave imager and THz spectroscopy to efficiently identify different volatile liquids

    Virtual reality training in cardiopulmonary resuscitation in schools

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    This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of Paramedic Practice, copyright © MA Education, after peer review and technical editing by the publisher. To access the final edited and published work see https://www.magonlinelibrary.com/doi/abs/10.12968/jpar.2021.13.9.365UK average survival from Out of Hospital Cardiac Arrest (OHCA) survival is around 8.6%, which is significantly lower than other high performing countries with survival rates of over 20%. A cardiac arrest victim is 2–4 times more likely to survive OHCA with bystander CPR provision. Mandatory Teaching CPR to children in school is acknowledged to be the most effective way to reach the entire population and improving the bystander CPR rate and is endorsed by the World Health Organization (WHO) “Kids Save Lives” statement. Despite this, Wales is yet to follow other home nations by including CPR training as a mandatory within the school’s curriculum. In this paper, we explore the role of teaching CPR to schoolchildren and report on the development by Computer scientists at the University of Chester and the Welsh Ambulance Services NHS Trust (WAST) of VCPR, a virtual environment to help teach the procedure. VCPR was developed in three stages: identifying requirements and specifications; development of a prototype; and management—development of software, further funding and exploring opportunities for commercialisation. We describe the opportunities in Wales to skill up the whole population over time in CPR and present our Virtual reality (VR) technology is emerging as a powerful for teaching CPR in schools

    Re-purposing evaluation to learn about social justice: Reconfiguring epistemological politics through the regulative ideal of ‘participatory parity’

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    From SAGE Publishing via Jisc Publications RouterHistory: epub 2020-12-24Publication status: PublishedFunder: Economic and Social Research Council; FundRef: https://doi.org/10.13039/501100000269; Grant(s): 1504165The article aims to re-purpose evaluation to learn about social justice by anchoring evaluation in normative dimensions. This article demonstrates the ways in which evaluation with an establishment orientation can limit the scope for dialogue and neglect narratives that contest the status quo. It explains how a more participatory approach that engages with the standpoints of marginalised participants can enhance the potential to learn about social justice. An ethical commitment to social justice does not mean a rejection of rigour in evidence-based evaluation. Relating Fraser’s critical theory of participatory parity to the regulative ideal of evaluation creates a foundation to systematically foreground explanations about how an intervention has delivered social justice

    The T cell receptor repertoire of tumor infiltrating T cells is predictive and prognostic for cancer survival.

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    From Europe PMC via Jisc Publications RouterHistory: ppub 2021-07-01, epub 2021-07-02Publication status: PublishedFunder: Wellcome Trust; Grant(s): 100282/Z/12/ZFunder: Cancer Research UK; Grant(s): A22902, A27412Tumor infiltration by T cells is paramount for effective anti-cancer immune responses. We hypothesized that the T cell receptor (TCR) repertoire of tumor infiltrating T lymphocytes could therefore be indicative of the functional state of these cells and determine disease course at different stages in cancer progression. Here we show that the diversity of the TCR of tumor infiltrating T cell at baseline is prognostic in various cancers, whereas the TCR clonality of T cell infiltrating metastatic melanoma pre-treatment is predictive for activity and efficacy of PD1 blockade immunotherapy

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