Subpopulations of liver coated vesicles resolved by preparative agarose gel electrophoresis.

Rat liver clathrin coated vesicles (CVs) were separated into several distinct subpopulations using non-sieving concentrations of agarose, which allowed the separation of species differing primarily in surface charge. Using preparative agarose electrophoresis (Kedersha, N. L., and L. H. Rome, 1986, Anal. Biochem., in press), the CVs were recovered and analyzed for differences in morphology, coat protein composition, and stripped vesicle protein composition. Coat proteins from different populations appeared identical on SDS PAGE, and triskelions stripped from the different populations showed the same mobility on the agarose gel, suggesting that the mobility differences observed in intact CVs were due to differences in the surface charge of underlying vesicles rather than to variations in their clathrin coats. Several non-coat polypeptides appeared to segregate exclusively with different populations as resolved by two-dimensional electrophoresis. Stripped CVs also exhibited considerable heterogeneity when analyzed by Western blotting: the fast-migrating population was enriched in the mannose 6-phosphate receptor, secretory acetylcholine esterase, and an Mr 195,000 glycoprotein. The slow-migrating population of CVs was enriched in the asialoglycoprotein receptor, and it appeared to contain all detectable concanavalin A-binding polypeptides as well as the bulk of detectable WGA-binding proteins. When CVs were prepared from 125I-asialoorosomucoid-perfused rat liver, ligand was found in the slow-migrating CVs, suggesting that these were endocytic in origin. Morphological differences were also observed: the fast-migrating population was enriched in smaller CVs, whereas the slow-migrating population exhibited an enrichment in larger CVs. As liver consists largely of hepatocytes, these subpopulations appear to originate from the same cell type and probably represent CVs of different intracellular origin and destination

Remote sensing of glacier change in the Central Qinghai-Tibet Plateau and the relationship with changing climate

2016-2017 > Academic research: refereed > Publication in refereed journal201804_a bcmaVersion of RecordPublishe

Brachial and Cerebrovascular Functions Are Enhanced in Postmenopausal Women after Ingestion of Chocolate with a High Concentration of Cocoa.

Background: Cocoa contains polyphenols that are thought to be beneficial for vascular health.Objective: We assessed the impact of chocolate containing distinct concentrations of cocoa on cerebrovascular function and cognition.Methods: Using a counterbalanced within-subject design, we compared the acute impact of consumption of energy-matched chocolate containing 80%, 35%, and 0% single-origin cacao on vascular endothelial function, cognition, and cerebrovascular function in 12 healthy postmenopausal women (mean ± SD age: 57.3 ± 5.3 y). Participants attended a familiarization session, followed by 3 experimental trials, each separated by 1 wk. Outcome measures included cerebral blood flow velocity (CBFv) responses, recorded before and during completion of a computerized cognitive assessment battery (CogState); brachial artery flow-mediated dilation (FMD); and hemodynamic responses (heart rate and blood pressure).Results: When CBFv data before and after chocolate intake were compared between conditions through the use of 2-factor ANOVA, an interaction effect (P = 0.003) and main effects for chocolate (P = 0.043) and time (P = 0.001) were evident. Post hoc analysis revealed that both milk chocolate (MC; 35% cocoa; P = 0.02) and dark chocolate (DC; 80% cocoa; P = 0.003) induced significantly lower cerebral blood flow responses during the cognitive tasks, after normalizing for changes in arterial pressure. DC consumption also increased brachial FMD compared with the baseline value before chocolate consumption (P = 0.002), whereas MC and white chocolate (0% cocoa) caused no change (P-interaction between conditions = 0.034).Conclusions: Consumption of chocolate containing high concentrations of cocoa enhanced vascular endothelial function, which was reflected by improvements in FMD. Cognitive function outcomes did not differ between conditions; however, cerebral blood flow responses during these cognitive tasks were lower in those consuming MC and DC. These findings suggest that chocolate containing high concentrations of cocoa may modify the relation between cerebral metabolism and blood flow responses in postmenopausal women. This trial was registered at www.ANZCTR.orgau as ACTRN12616000990426

Acceptability of aspirin for cancer preventive therapy: a survey and qualitative study exploring the views of the UK general population

OBJECTIVES: Aspirin could be offered for colorectal cancer prevention for the UK general population. To ensure the views of the general population are considered in future guidance, we explored public perceptions of aspirin for preventive therapy. DESIGN: We conducted an online survey to investigate aspirin use, and awareness of aspirin for cancer prevention among the UK general population. We conducted semistructured interviews with a subsample of survey respondents to explore participants' acceptability towards aspirin for cancer preventive therapy. We analysed the interview data using reflexive thematic analysis and mapped the themes onto the Theoretical Domains Framework, and the Necessity and Concerns Framework. SETTING: Online survey and remote interviews. PARTICIPANTS: We recruited 400 UK respondents aged 50-70 years through a market research company to the survey. We purposefully sampled, recruited and interviewed 20 survey respondents. RESULTS: In the survey, 19.0% (76/400) of respondents were aware that aspirin can be used to prevent cancer. Among those who had previously taken aspirin, 1.9% (4/216) had taken it for cancer prevention. The interviews generated three themes: (1) perceived necessity of aspirin; (2) concerns about side effects; and (3) preferred information sources. Participants with a personal or family history of cancer were more likely to perceive aspirin as necessary for cancer prevention. Concerns about taking aspirin at higher doses and its side effects, such as gastrointestinal bleeding, were common. Many described wanting guidance and advice on aspirin to be communicated from sources perceived as trustworthy, such as healthcare professionals. CONCLUSIONS: Among the general population, those with a personal or family history of cancer may be more receptive towards taking aspirin for preventive therapy. Future policies and campaigns recommending aspirin may be of particular interest to these groups. Multiple considerations about the benefits and risks of aspirin highlight the need to support informed decisions on the medication

Breast cancer worry in higher-risk women offered preventive therapy: a UK multicentre prospective study

Purpose Women’s worry about developing breast cancer may influence their decision to use preventive therapy. However, the direction of this relationship has been questioned. We prospectively investigated the relationship between breast cancer worry and uptake of preventive therapy. The socio-demographic and clinical factors associated with high breast cancer worry were also investigated. Methods Women at increased risk of developing breast cancer were recruited from clinics across England (n = 408). Participants completed a survey on their breast cancer worry, socio-demographic and clinical factors. Uptake of tamoxifen was recorded at 3 months (n = 258 women, 63.2%). Both primary and sensitivity analyses were conducted using different classifications of low, medium and high worry. Results 39.5% of respondents reported medium breast cancer worry at baseline and 21.2% reported high worry. Ethnic minority women were more likely to report high worry than white women (OR = 3.02, 95%CI 1.02, 8.91, p = 0.046). Women educated below degree level were more likely to report high worry than those with higher education (OR = 2.29, 95%CI 1.28, 4.09, p = 0.005). No statistically significant association was observed between worry and uptake. In the primary analysis, fewer respondents with medium worry at baseline initiated tamoxifen (low worry = 15.5%, medium = 13.5%, high = 15.7%). In the sensitivity analysis, participants with medium worry reported the highest uptake of tamoxifen (19.7%). Conclusions No association was observed between worry and uptake, although the relationship was affected by the categorisation of worry. Standardised reporting of the classification of worry is warranted to allow transparent comparisons across cohorts

GPs' willingness to prescribe aspirin for cancer preventive therapy in Lynch syndrome: a factorial randomised trial investigating factors influencing decisions.

BACKGROUND: The National Institute for Health and Care Excellence (NICE) 2020 guidelines recommends aspirin for colorectal cancer prevention for people with Lynch syndrome. Strategies to change practice should be informed by understanding the factors influencing prescribing. AIM: To investigate the optimal type and level of information to communicate with GPs to increase willingness to prescribe aspirin. DESIGN AND SETTING: GPs in England and Wales (n = 672) were recruited to participate in an online survey with a 23 factorial design. GPs were randomised to one of eight vignettes describing a hypothetical patient with Lynch syndrome recommended to take aspirin by a clinical geneticist. METHOD: Across the vignettes, the presence or absence of three types of information was manipulated: 1) existence of NICE guidance; 2) results from the CAPP2 trial; 3) information comparing risks/benefits of aspirin. The main effects and all interactions on the primary (willingness to prescribe) and secondary outcomes (comfort discussing aspirin) were estimated. RESULTS: There were no statistically significant main effects or interactions of the three information components on willingness to prescribe aspirin or comfort discussing harms and benefits. In total, 80.4% (540/672) of GPs were willing to prescribe, with 19.7% (132/672) unwilling. GPs with prior awareness of aspirin for preventive therapy were more comfortable discussing the medication than those unaware (P = 0.031). CONCLUSION: It is unlikely that providing information on clinical guidance, trial results, and information comparing benefits and harms will increase aspirin prescribing for Lynch syndrome in primary care. Alternative multilevel strategies to support informed prescribing may be warranted

Acceptability of aspirin for cancer preventive therapy: a survey and qualitative study exploring the views of the UK general population.

OBJECTIVES: Aspirin could be offered for colorectal cancer prevention for the UK general population. To ensure the views of the general population are considered in future guidance, we explored public perceptions of aspirin for preventive therapy. DESIGN: We conducted an online survey to investigate aspirin use, and awareness of aspirin for cancer prevention among the UK general population. We conducted semistructured interviews with a subsample of survey respondents to explore participants' acceptability towards aspirin for cancer preventive therapy. We analysed the interview data using reflexive thematic analysis and mapped the themes onto the Theoretical Domains Framework, and the Necessity and Concerns Framework. SETTING: Online survey and remote interviews. PARTICIPANTS: We recruited 400 UK respondents aged 50-70 years through a market research company to the survey. We purposefully sampled, recruited and interviewed 20 survey respondents. RESULTS: In the survey, 19.0% (76/400) of respondents were aware that aspirin can be used to prevent cancer. Among those who had previously taken aspirin, 1.9% (4/216) had taken it for cancer prevention. The interviews generated three themes: (1) perceived necessity of aspirin; (2) concerns about side effects; and (3) preferred information sources. Participants with a personal or family history of cancer were more likely to perceive aspirin as necessary for cancer prevention. Concerns about taking aspirin at higher doses and its side effects, such as gastrointestinal bleeding, were common. Many described wanting guidance and advice on aspirin to be communicated from sources perceived as trustworthy, such as healthcare professionals. CONCLUSIONS: Among the general population, those with a personal or family history of cancer may be more receptive towards taking aspirin for preventive therapy. Future policies and campaigns recommending aspirin may be of particular interest to these groups. Multiple considerations about the benefits and risks of aspirin highlight the need to support informed decisions on the medication

Violence and vulnerability:Children’s strategies and the logic of violence in Burundi

This study explores how children in conflict-affected Burundi deal with violence in their everyday lives. Focusing on schools as a context in which children are prepared for further roles in society, child-centred, qualitative and mixed-methods research was conducted at 36 primary schools throughout Burundi. Findings reveal that children use a variety of strategies to deal with violence they encounter. These strategies reflect a learned 'logic of violence', matching dynamics of violence and vulnerability in society at large. Children's strategies are ultimately aimed at reducing vulnerability to (future) violence and indicative of the omnipresence of violence and uncertainty in Burundi. (C) 2019 The Authors. Children & Society published by National Children's Bureau and John Wiley & Sons LtdPublic Health and primary car

Coarse-grained reconfigurable array architectures

Coarse-Grained Reconfigurable Array (CGRA) architectures accelerate the same inner loops that benefit from the high ILP support in VLIW architectures. By executing non-loop code on other cores, however, CGRAs can focus on such loops to execute them more efficiently. This chapter discusses the basic principles of CGRAs, and the wide range of design options available to a CGRA designer, covering a large number of existing CGRA designs. The impact of different options on flexibility, performance, and power-efficiency is discussed, as well as the need for compiler support. The ADRES CGRA design template is studied in more detail as a use case to illustrate the need for design space exploration, for compiler support and for the manual fine-tuning of source code

Cooperative secretions facilitate host range expansion in bacteria

The majority of emergent human pathogens are zoonotic in origin, that is, they can transmit to humans from other animals. Understanding the factors underlying the evolution of pathogen host range is therefore of critical importance in protecting human health. There are two main evolutionary routes to generalism: organisms can tolerate multiple environments or they can modify their environments to forms to which they are adapted. Here we use a combination of theory and a phylogenetic comparative analysis of 191 pathogenic bacterial species to show that bacteria use cooperative secretions that modify their environment to extend their host range and infect multiple host species. Our results suggest that cooperative secretions are key determinants of host range in bacteria, and that monitoring for the acquisition of secreted proteins by horizontal gene transfer can help predict emerging zoonoses