Endothelial HO-1 induction by model TG-rich lipoproteins is regulated through a NOX4-Nrf2 pathway

Circulating levels of chylomicron remnants (CMRs) increase postprandially and their composition directly reflects dietary lipid intake. These TG-rich lipoproteins likely contribute to the development of endothelial dysfunction, albeit via unknown mechanisms. Here, we investigated how the FA composition of CMRs influences their actions on human aortic endothelial cells (HAECs) by comparing the effects of model CMRs—artificial TG-rich CMR-like particles (A-CRLPs)—containing TGs extracted from fish, DHA-rich algal, corn, or palm oils. HAECs responded with distinct transcriptional programs according to A-CRLP TG content and oxidation status, with genes involved in antioxidant defense and cytoprotection most prominently affected by n-3 PUFA-containing A-CRLPs. These particles were significantly more efficacious inducers of heme oxygenase-1 (HO-1) than n-6 PUFA corn or saturated FA-rich palm CRLPs. Mechanistically, HO-1 induction by all CRLPs requires NADPH oxidase 4, with PUFA-containing particles additionally dependent upon mitochondrial reactive oxygen species. Activation of both p38 MAPK and PPARβ/δ culminates in increased nuclear factor erythroid 2-related factor 2 (Nrf2) expression/nuclear translocation and HO-1 induction. These studies define new molecular pathways coupling endothelial cell activation by model CMRs with adaptive regulation of Nrf2-dependent HO-1 expression and may represent key mechanisms through which dietary FAs differentially impact progression of endothelial dysfunction

Imaging Flaws in Thin Metal Plates Using a Magneto-Optic Device

The ability to quickly detect flaws in thin aluminum alloy sheets is of critical importance to the commercial airline fleets. Current eddy-current methods, although very effective at exposing flawed regions, can be very time consuming when applied to airframe structures. The need for a fast, effective means of detecting critical flaws needs to be met. The purpose of this paper is to present preliminary results describing some capabilities of a new instrument, The Magneto-Optic/Eddy Current Imager, as an NDE tool for use in the Airframe Structural Integrity Program

Concerns, perceived need and competing priorities: a qualitative exploration of decision-making and non-participation in a population-based flexible sigmoidoscopy screening programme to prevent colorectal cancer.

OBJECTIVE: Optimising uptake of colorectal cancer (CRC) screening is important to achieve projected health outcomes. Population-based screening by flexible sigmoidoscopy (FS) was introduced in England in 2013 (NHS Bowel scope screening). Little is known about reactions to the invitation to participate in FS screening, as offered within the context of the Bowel scope programme. We aimed to investigate responses to the screening invitation to inform understanding of decision-making, particularly in relation to non-participation in screening. DESIGN: Qualitative analysis of semistructured in-depth interviews and written accounts. PARTICIPANTS AND SETTING: People from 31 general practices in the North East and East of England invited to attend FS screening as part of NHS Bowel scope screening programme were sent invitations to take part in the study. We purposively sampled interviewees to ensure a range of accounts in terms of beliefs, screening attendance, sex and geographical location. RESULTS: 20 screeners and 25 non-screeners were interviewed. Written responses describing reasons for, and circumstances surrounding, non-participation from a further 28 non-screeners were included in the analysis. Thematic analysis identified a range of reactions to the screening invitation, decision-making processes and barriers to participation. These include a perceived or actual lack of need; inability to attend; anxiety and fear about bowel preparation, procedures or hospital; inability or reluctance to self-administer an enema; beliefs about low susceptibility to bowel cancer or treatment and understanding of harm and benefits. The strength, rather than presence, of concerns about the test and perceived need for reassurance were important in the decision to participate for screeners and non-screeners. Decision-making occurs within the context of previous experiences and day-to-day life. CONCLUSIONS: Understanding the reasons for non-participation in FS screening can help inform strategies to improve uptake and may be transferable to other screening programmes

Varicella-zoster virus induces apoptosis in cell culture

peer reviewedaudience: researcherApoptosis is an active mechanism of cell death which can be initiated in response to various stimuli including virus infections. In this work, we demonstrate that lytic infection by varicella-zoster virus (VZV), a human herpesvirus, is characterized by nuclear fragmentation of DNA into oligonucleosomal fragments and by chromatin condensation. In vitro, VZV-induced cell death is actually mediated by apoptosis. The mechanisms developed by cells to protect themselves against apoptosis could be one of the parameters allowing the establishment of virus latency. In the case of VZV, which can remain latent in sensory ganglia, we have not yet identified a cellular or viral protein which could play this protective role, since the observed apoptosis mechanism seems to be independent from Bcl-2, the most frequently described inhibitor of apoptosis

Understanding symptom appraisal and help-seeking in people with symptoms suggestive of pancreatic cancer: a qualitative study

Objective: Pancreatic cancer has poor survival rates due to non-specific symptoms leading to later diagnosis. Understanding how patients interpret their symptoms could inform approaches to earlier diagnosis. This study sought to explore symptom appraisal and help-seeking among patients referred to secondary care for symptoms suggestive of pancreatic cancer. Design: Qualitative analysis of semistructured in-depth interviews. Data were analysed iteratively and thematically, informed by the Model of Pathways to Treatment. Participants and setting: Pancreatic cancer occurs rarely in younger adults, therefore patients aged ≥40 years were recruited from nine hospitals after being referred to hospital with symptoms suggestive of pancreatic cancer; all were participants in a cohort study. Interviews were conducted soon after referral, and where possible, before diagnosis. Results: Twenty-six interviews were conducted (cancer n=13 (pancreas n=9, other intra-abdominal n=4), non-cancer conditions n=13; age range 48–84 years; 14 women). Time from first symptoms to first presentation to healthcare ranged from 1 day to 270 days, median 21 days. We identified three main themes. Initial symptom appraisal usually began with intermittent, non-specific symptoms such as tiredness or appetite changes, attributed to diet and lifestyle, existing gastrointestinal conditions or side effects of medication. Responses to initial symptom appraisal included changes in meal type or frequency, or self-medication. Symptom changes such as alterations in appetite and enjoyment of food or weight loss usually prompted further appraisal. Triggers to seek help included a change or worsening of symptoms, particularly pain, which was often a ‘tipping point’. Help-seeking was often encouraged by others. We found no differences in symptom appraisal and help-seeking between people diagnosed with cancer and those with other conditions. Conclusions: Greater public and healthcare professional awareness of the combinations of subtle and intermittent symptoms, and their evolving nature, is needed to prompt timelier help-seeking and investigation among people with symptoms of pancreatic cancer

The most creative organization in the world? The BBC, 'creativity' and managerial style

The managerial styles of two BBC directors-general, John Birt and Greg Dyke, have often been contrasted but not so far analysed from the perspective of their different views of 'creative management'. This article first addresses the orthodox reading of 'Birtism'; second, it locates Dyke's 'creative' turn in the wider context of fashionable neo-management theory and UK government creative industries policy; third, it details Dyke's drive to change the BBC's culture; and finally, it concludes with some reflections on the uncertainties inherent in managing a creative organisation

Nitrogen fertilizer rate but not form affects the severity of Fusarium wilt in banana

Nitrogen (N) fertilizers are routinely applied to bananas (Musa spp.) to increase production but may exacerbate plant diseases like Fusarium wilt of banana (FWB), which is the most economically important disease. Here, we characterized the effects of N rate and form on banana plant growth, root proteome, bacterial and fungal diversity in the rhizosphere, the concentration of Fusarium oxysporum f.sp. cubense (Foc) in the soil, and the FWB severity. Banana plants (Musa subgroup ABB) were grown under greenhouse conditions in soil with ammonium or nitrate supplemented at five N rates, and with or without inoculation with Foc. The growth of non-inoculated plants was positively correlated with the N rate. In bananas inoculated with Foc, disease severity increased with the N rate, resulting in the Foc-inoculated plant growth being greatest at intermediate N rates. The abundance of Foc in the soil was weakly related to the treatment conditions and was a poor predictor of disease severity. Fungal diversity was consistently affected by Foc inoculation, while bacterial diversity was associated with changes in soil pH resulting from N addition, in particular ammonium. N rate altered the expression of host metabolic pathways associated with carbon fixation, energy usage, amino acid metabolism, and importantly stress response signaling, irrespective of inoculation or N form. Furthermore, in diseased plants, Pathogenesis-related protein 1, a key endpoint for biotic stress response and the salicylic acid defense response to biotrophic pathogens, was negatively correlated with the rate of ammonium fertilizer but not nitrate. As expected, inoculation with Foc altered the expression of a wide range of processes in the banana plant including those of defense and growth. In summary, our results indicate that the severity of FWB was negatively associated with host defenses, which was influenced by N application (particularly ammonium), and shifts in microbial communities associated with ammonium-induced acidification. Copyright © 2022 Orr, Dennis, Wong, Browne, Cooper, Birt, Lapis-Gaza, Pattison and Nelson

A large-scale experiment finds no evidence that a seismic survey impacts a demersal fish fauna

Seismic surveys are used to locate oil and gas reserves below the seabed and can be a major source of noise in marine environments. Their effects on commercial fisheries are a subject of debate, with experimental studies often producing results that are difficult to interpret. We overcame these issues in a large-scale experiment that quantified the impacts of exposure to a commercial seismic source on an assemblage of tropical demersal fishes targeted by commercial fisheries on the North West Shelf of Western Australia. We show that there were no short-term (days) or long-term (months) effects of exposure on the composition, abundance, size structure, behavior, or movement of this fauna. These multiple lines of evidence suggest that seismic surveys have little impact on demersal fishes in this environment