Identification through microarray gene expression analysis of cellular responses to benzo(a)pyrene and its diol-epoxide that are dependent or independent of p53

Human colon carcinoma cells (HCT116) differing in p53 status were exposed to benzo(a)pyrene (BaP) or anti-benzo(a)pyrene-trans-7,8-dihydrodiol-9,10-epoxide (BPDE) and their gene expression responses compared by complementary DNA microarray technology. Exposure of cells to BPDE for up to 24 h resulted in gene expression profiles more distinguishable by duration of exposure than by p53 status, although a subset of genes were identified that had significantly different expression in p53 wild-type (WT) cells relative to p53-null cells. Apoptotic signalling genes were up-regulated in p53-WT cells but not in p53-null cells and, consistent with this, reduced viability and caspase activity were also p53 dependent. BPDE modulated cell cycle and histone genes in both cell lines and, in agreement with this, both cell lines accumulated in S phase. In p53-WT cells, G(2) arrest was also evident, which was associated with accumulation of CDKN1A. Regardless of p53 status, exposure to BaP for up to 48 h had subtle effects on gene transcription and had no influence on cell viability or cell cycle. Interestingly, DNA adduct formation after BaP, but not BPDE, exposure was p53 dependent with 10-fold lower levels detected in p53-null cells. Other cell lines were investigated for BaP-DNA adduct formation and in these the effect of p53 knockdown was also to reduce adduct formation. Taken together, these results give further insight into the role of p53 in the response of human cells to BaP and BPDE and suggest that loss of this tumour suppressor can influence the metabolic activation of BaP

Gene expression profiles modulated by the human carcinogen aristolochic acid I in human cancer cells and their dependence on TP53

Aristolochic acid (AA) is the Causative agent of urothelial tumours associated with aristolochic acid nephropathy. These tumours contain TP53 mutations and over-express TP53. We compared transcriptional and translational responses of two isogenic HCT116 cell lines, one expressing TP53 (p53-WT) and the other with this gene knocked out (p53-null), to treatment with aristolochic acid I (AAI) (50-100 mu M) lor 6-48 h. Modulation of 118 genes was observed in p53-WT cells ad 123 genes in p53-null cells. Some genes, including INSIG1, EGR1, CAV1, LCN2 arid CCNG1, were differentially expressed in the two cell lines. CDKN1A was selectively Up-regulated in p53-WT cells, leading to accumulation of TP53 and CDKN1A. Apoptotic signalling, measured by caspase-3 and -7 activity, was TP53-dependent. Both cell types accumulated in S phase, suggesting that AAI-DNA adducts interfere with DNA replication, independently of TP53 Status. The oncogene MYC, frequently over expressed ill urothelial turnouts, Was Up-regulated by AAI, whereas FOS was down-regulated. Observed modulation of genes involved in endocytosis, e.g. RAB5A, may be relevant to the known inhibition of receptor-mediated endocytosis, an early sign of AA-mediated proximal tubule injury. AAI-DNA adduct Formation was significantly greater in p53-WT cells than in p53-null cells. Collectively, phenotypic anchoring of the AAI-induced expression profiles to DNA adduct formation, cell-cycle parameters, TP53 expression arid apoptosis identified several genes linked to these biological outcomes, some of which are TP53-dependent. These results strengthen the importance of TP53 in AA-induced cancer, arid indicate that other alterations, e.g. to MYC oncogenic pathways, may also contribute. (C) 2008 Elsevier Inc. All rights reserved

Human well-being impacts of terrestrial protected areas

© 2013 Pullin et al.; licensee BioMed Central Ltd. Background: Establishing Protected Areas (PAs) is among the most common conservation interventions. Protecting areas from the threats posed by human activity will by definition inhibit some human actions. However, adverse impacts could be balanced by maintaining ecosystem services or introducing new livelihood options. Consequently there is an ongoing debate on whether the net impact of PAs on human well-being at local or regional scales is positive or negative. We report here on a systematic review of evidence for impacts on human well-being arising from the establishment and maintenance of terrestrial PAs. Methods: Following an a priori protocol, systematic searches were conducted for evidence of impacts of PAs post 1992. After article title screening, the review was divided into two separate processes; a qualitative synthesis of explanations and meaning of impact and a review of quantitative evidence of impact. Abstracts and full texts were assessed using inclusion criteria and conceptual models of potential impacts. Relevant studies were critically appraised and data extracted and sorted according to type of impact reported. No quantitative synthesis was possible with the evidence available. Two narrative syntheses were produced and their outputs compared in a metasynthesis. Results: The qualitative evidence review mapped 306 articles and synthesised 34 that were scored as high quality. The quantitative evidence review critically appraised 79 studies and included 14 of low/medium susceptibility to bias. The meta-synthesis reveals that a range of factors can lead to reports of positive and negative impacts of PA establishment, and therefore might enable hypothesis generation regarding cause and effect relationships, but resulting hypotheses cannot be tested with the current available evidence. Conclusions: The evidence base provides a range of possible pathways of impact, both positive and negative, of PAs on human well-being but provides very little support for decision making on how to maximise positive impacts. The nature of the research reported to date forms a diverse and fragmented body of evidence unsuitable for the purpose of informing policy formation on how to achieve win-win outcomes for biodiversity and human well-being. To better assess the impacts of PAs on human well-being we make recommendations for improving research study design and reporting

COVID, communication and care homes:A staffs’ perspective of supporting the emotional needs of families

An important part of care home life is the support given to older residents by their families/friends through regular visiting. Social visits to residents by their families ceased in response to the COVID-19 pandemic and residents were confined to their rooms. This paper reports on how care home staff improvised to address this situation during the first wave of the pandemic. It focuses on steps taken to maintain communication between residents and families to support emotional well-being. We undertook in-depth café-style interviews with twenty-one staff to explore creative practices that they introduced. It was part of a wider Scottish study examining the effect of lockdown on families whose relative was living/dying in a care home (May–October, 2020). Findings reveal the enormous effort by care staff to maintain family connections and the rapid acclimatisation involved working with a number of different on-line platforms, the pulling together of staff from across the care home, and, the attention to emotional well-being of residents living and dying in the care home. Findings highlight the professionalism and commitment of the leadership and staff involved. Whilst some of the staff accounts need no further comment, we draw on some themes from the care home research literature to make sense of the findings in terms of what we might learn going forward. This in-depth qualitative study emphasises the importance of recognising, fostering and nurturing relational compassionate care within long-term care. There is however little evidence whether health and social care policies recognise the importance of this on-going relationship

Understanding and Reducing the Psychosocial Impact of Coronavirus Social Distancing and Behavioural Changes on Families of Care Home Residents in Scotland

Project Report Aims This project examined the impact of social distancing on care home communities as a result of lockdown to minimise threats of COVID-19 with a particular focus on the health and well-being of family carers and investigated measures taken by care home staff to help families to stay in touch with their relatives in care homes. Key findings The Importance of visits: The experience of being unable to visit their loved ones during the pandemic had a negative impact upon the emotional well-being of the study participants. In our interviews, the inability to touch and see their loved ones caused multiple negative emotions. This was supported by the survey data in which 76% of participants gave responses indicating mental distress. Significance of prior trust: The pandemic has heightened the significance of prior trust in care home staff and management, and the importance of frequent effective communication building trust and confidence when relatives are no longer in the building and able to see good practice in action. COVID-19 led to creative changes in care home practices: Care home staff instituted greater pro-active communication with relatives, and staff reported enhanced confidence in their communication with families. Staff also made great use of digital technology to facilitate communication between residents, family carers and themselves. There was a widely expressed belief that many of these changes could be built on to improve care home practices in the future. Maintaining communication is crucial. Analysis from the survey suggests that respondents who felt they were kept well-informed by the care home on average experienced less mental distress than those who did not. Lack of insight into the impact of lockdown on family carers. Most policy makers and leading figures in the sector had a superficial understanding of the impact of lockdown on family carers. In particular, there was little acknowledgement of family carers as partners in providing care and the importance of that relationship to both care-giver and care-receiver. Human rights. There was a widely expressed concern that the human right to a family life had not been adequately balanced against the risks of infection. Impact on marginalised communities. There was a recognition the pandemic has revealed how little we value older people with dementia within our society and the needs of black and minority ethnic communities. National Guidance. The mixed economy of care home providers meant that it was extremely difficult to implement national guidance in a manner which was consistent, equitable and appropriate across the whole sector

Genome-wide linkage screen for testicular germ cell tumour susceptibility loci

A family history of disease is a strong risk factor for testicular germ cell tumour (TGCT). In order to identify the location of putative TGCT susceptibility gene(s) we conducted a linkage search in 237 pedigrees with two or more cases of TGCT. One hundred and seventy-nine pedigrees were evaluated genome-wide with an average inter-marker distance of 10 cM. An additional 58 pedigrees were used to more intensively investigate several genomic regions of interest. Genetic linkage analysis was performed with the ALLEGRO software using two model-based parametric analyses and a non-parametric analysis. Six genomic regions on chromosomes 2p23, 3p12, 3q26, 12p13-q21, 18q21-q23 and Xq27 showed heterogeneity LOD (HLOD) scores of greater than 1, with a maximum HLOD of 1.94 at 3q26. Genome-wide simulation studies indicate that the observed number of HLOD peaks greater than one does not differ significantly from that expected by chance. A TGCT locus at Xq27 has been previously reported. Of the 237 pedigrees examined in this study, 66 were previously unstudied at Xq27, no evidence for linkage to this region was observed in this new pedigree set. Overall, the results indicate that no single major locus can account for the majority of the familial aggregation of TGCT, and suggests that multiple susceptibility loci with weak effects contribute to the diseas

Environmental cues on sorting behaviour

This report outlines the research experiment conducted by three psychology students from the University of British Columbia and their findings on environmental cues and the effects they pose towards sorting behaviours. The study was sanctioned by the Zero Waste Project at UBC and was designed to answer the following questions—How is sorting behaviour impacted by having stand-alone garbage cans inside, or just outside, large auditoriums? And is there a benefit to having a poster where the garbage was asking people to recycle? The research was conducted using a 2 x 2 between-subjects factorial design, participants were randomly assigned to one of four conditions; each consisting of a different combination of environmental cues. Sorting behaviour was operationalized by the participants disposal of the experiment’s designated material, as collected in the Sort it Out bin. The research findings indicate certain benefits to having environmentally prompting cues in place of garbage cans in auditoriums, as supported by the data collected on sorting behaviours of the participants. Further studies need be conducted before determining conclusive results; until then the Zero Waste Project will continue to promote environmentally sustainable initiatives to reach UBC’s greener goals. Disclaimer: “UBC SEEDS provides students with the opportunity to share the findings of their studies, as well as their opinions, conclusions and recommendations with the UBC community. The reader should bear in mind that this is a student project/report and is not an official document of UBC. Furthermore readers should bear in mind that these reports may not reflect the current status of activities at UBC. We urge you to contact the research persons mentioned in a report or the SEEDS Coordinator about the current status of the subject matter of a project/report.”Arts, Faculty ofPsychology, Department ofUnreviewedUndergraduat

Galanin suppresses visceral afferent responses to noxious mechanical and inflammatory stimuli.

Galanin is a neuropeptide expressed by sensory neurones innervating the gastrointestinal (GI) tract. Galanin displays inhibitory effects on vagal afferent signaling within the upper GI tract, and the goal of this study was to determine the actions of galanin on colonic spinal afferent function. Specifically, we sought to evaluate the effect of galanin on lumbar splanchnic nerve (LSN) mechanosensitivity to noxious distending pressures and the development of hypersensitivity in the presence of inflammatory stimuli and colitis. Using ex vivo electrophysiological recordings we show that galanin produces a dose-dependent suppression of colonic LSN responses to mechanical stimuli and prevents the development of hypersensitivity to acutely administered inflammatory mediators. Using galanin receptor (GalR) agonists, we show that GalR1 activation, but not GalR2/3 activation, suppresses mechanosensitivity. The effect of galanin on colonic afferent activity was not observed in tissue from mice with dextran sodium sulfate-induced colitis. We conclude that galanin has a marked suppressive effect on colonic mechanosensitivity at noxious distending pressures and prevents the acute development of mechanical hypersensitivity to inflammatory mediators, an effect not seen in the inflamed colon. These actions highlight a potential role for galanin in the regulation of mechanical nociception in the bowel and the therapeutic potential of targeting galaninergic signaling to treat visceral hypersensitivity

Data to support: Galanin suppresses visceral afferent responses to noxious mechanical and inflammatory stimuli

Data sets containing raw data used in the figures for the paper and example images.BBSRC (BB/R006210/1), Rosetrees (A1296), Vice Chancellor's Trust Awar