Determining the Age of Young Embedded Clusters

A new Monte Carlo method has been developed in order to derive ages of young embedded clusters within massive star forming regions where there is strong differential reddening. After foreground and infrared excess source candidates are removed, each cluster candidate star is individually dereddened. Simulated clusters are constructed using isochrones, an IMF, realistic photometric errors, simulated background field populations and extinction distributions. These synthetic clusters are then dereddened in the same way as the real data, obtained from a deep near infrared survey, and used to derive the ages of 3 embedded clusters. Results were found to be consistent with those determined using spectrophotometric methods. This new method provides way to determine the ages of embedded clusters when only photometric data are available and there is strong differential reddening.Comment: Accepted by MNRAS 27/07/1

Impact of Provider Self-Management Education, Patient Self-Efficacy, and Health Status on Patient Adherence in Heart Failure in a Veterans Administration Population

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73786/1/j.1751-7133.2008.07174.x.pd

The effectiveness of interventions to change six health behaviours: a review of reviews

Background: Several World Health Organisation reports over recent years have highlighted the high incidence of chronic diseases such as diabetes, coronary heart disease and cancer. Contributory factors include unhealthy diets, alcohol and tobacco use and sedentary lifestyles. This paper reports the findings of a review of reviews of behavioural change interventions to reduce unhealthy behaviours or promote healthy behaviours. We included six different health-related behaviours in the review: healthy eating, physical exercise, smoking, alcohol misuse, sexual risk taking (in young people) and illicit drug use. We excluded reviews which focussed on pharmacological treatments or those which required intensive treatments (e. g. for drug or alcohol dependency). Methods: The Cochrane Library, Database of Abstracts of Reviews of Effectiveness (DARE) and several Ovid databases were searched for systematic reviews of interventions for the six behaviours (updated search 2008). Two reviewers applied the inclusion criteria, extracted data and assessed the quality of the reviews. The results were discussed in a narrative synthesis. Results: We included 103 reviews published between 1995 and 2008. The focus of interventions varied, but those targeting specific individuals were generally designed to change an existing behaviour (e. g. cigarette smoking, alcohol misuse), whilst those aimed at the general population or groups such as school children were designed to promote positive behaviours (e. g. healthy eating). Almost 50% (n = 48) of the reviews focussed on smoking (either prevention or cessation). Interventions that were most effective across a range of health behaviours included physician advice or individual counselling, and workplace- and school-based activities. Mass media campaigns and legislative interventions also showed small to moderate effects in changing health behaviours. Generally, the evidence related to short-term effects rather than sustained/longer-term impact and there was a relative lack of evidence on how best to address inequalities. Conclusions: Despite limitations of the review of reviews approach, it is encouraging that there are interventions that are effective in achieving behavioural change. Further emphasis in both primary studies and secondary analysis (e.g. systematic reviews) should be placed on assessing the differential effectiveness of interventions across different population subgroups to ensure that health inequalities are addressed.</p

The Rewiring of Ubiquitination Targets in a Pathogenic Yeast Promotes Metabolic Flexibility, Host Colonization and Virulence

Funding: This work was funded by the European Research Council [http://erc.europa.eu/], AJPB (STRIFE Advanced Grant; C-2009-AdG-249793). The work was also supported by: the Wellcome Trust [www.wellcome.ac.uk], AJPB (080088, 097377); the UK Biotechnology and Biological Research Council [www.bbsrc.ac.uk], AJPB (BB/F00513X/1, BB/K017365/1); the CNPq-Brazil [http://cnpq.br], GMA (Science without Borders fellowship 202976/2014-9); and the National Centre for the Replacement, Refinement and Reduction of Animals in Research [www.nc3rs.org.uk], DMM (NC/K000306/1). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Acknowledgments We thank Dr. Elizabeth Johnson (Mycology Reference Laboratory, Bristol) for providing strains, and the Aberdeen Proteomics facility for the biotyping of S. cerevisiae clinical isolates, and to Euroscarf for providing S. cerevisiae strains and plasmids. We are grateful to our Microscopy Facility in the Institute of Medical Sciences for their expert help with the electron microscopy, and to our friends in the Aberdeen Fungal Group for insightful discussions.Peer reviewedPublisher PD

Cell membrane damage induced by phenolic acids on wine lactic acid bacteria

The aim of this work was to investigate the effect of phenolic acids on cell membrane permeability of lactic acid bacteria from wine. Several phenolic acids were tested for their effects on the cell membrane of Oenococcus oeni and Lactobacillus hilgardii by measuring potassium and phosphate efflux, proton influx and by assessing culture viability employing a fluorescence technique based on membrane integrity. The experimental results indicate that hydroxycinnamic acids (p-coumaric, caffeic and ferulic acids) induce greater ion leakages and higher proton influx than hydroxybenzoic acids (p-hydroxibenzoic, protocatechuic, gallic, vanillic, and syringic acids). Among the hydroxycinnamic acids, p-coumaric acid showed the strongest effect. Moreover, the exposure of cells to phenolic acids caused a significant decrease in cell culture viability, as measured by the fluorescence assay, in both tested strains. The results agree with previous results obtained in growth experiments with the same strains. Generally, phenolic acids increased the cell membrane permeability in lactic acid bacteria from wine. The different effects of phenolic acids on membrane permeability could be related to differences in their structure and lipophilic character

Strengthening clinical cancer research in the United Kingdom

BACKGROUND: In 1999, 270 000 cases of cancer were registered in the United Kingdom, placing a large burden on the NHS. Cancer outcome data in 1999 suggested that UK survival rates were poorer than most other European countries. In the same year, a Department of Health review noted that clinical trials accrual was poor (<3.5% of incident cases) and hypothesised that increasing research activity might improve outcomes and reduce the variability of outcomes across England. Thus, the National Cancer Research Network (NCRN) was established to increase participation in cancer clinical research.METHODS: The NCRN was established in 2001 to provide a robust infrastructure for cancer clinical research and improvements in patient care. Remit of NCRN is to coordinate, support and deliver cancer clinical research through the provision of research support staff across England. The NCRN works closely with similar networks in Scotland, Wales and the Northern Ireland. A key aim of NCRN is to improve the speed of research and this was also assessed by comparing the speed of study delivery of a subset of cancer studies opening before and after NCRN was established.RESULTS: Patient recruitment increased through NCRN, with almost 32 000 (12% of annual incident cases) cancer patients being recruited each year. Study delivery has improved, with more studies meeting the recruitment target - 74% compared with 39% before NCRN was established.CONCLUSION: The coordinated approach to cancer clinical research has demonstrated increased accrual, wide participation and successful trial delivery, which should lead to improved outcomes and care. British Journal of Cancer (2011) 104, 1529-1534. doi: 10.1038/bjc.2011.69 www.bjcancer.com Published online 1 March 2011 (C) 2011 Cancer Research U

Large Differences in Publicly Visible Health Behaviours across Two Neighbourhoods of the Same City

Background: There are socioeconomic disparities in the likelihood of adopting unhealthy behaviours, and success at giving them up. This may be in part because people living in deprived areas are exposed to greater rates of unhealthy behaviour amongst those living around them. Conventional self-report surveys do not capture these differences in exposure, and more ethological methods are required in order to do so. Methodology/Principal Findings: We performed 12 hours of direct behavioural observation in the streets of two neighbourhoods of the same city which were similar in most regards, except that one was much more socioeconomically deprived than the other. There were large differences in the publicly visible health behaviours observed. In the deprived neighbourhood, we observed 266 more adults smoking (rate ratio 3.44), 53 more adults drinking alcohol (rate ratio not calculable), and 38 fewer adults running (rate ratio 0.23), than in the affluent neighbourhood. We used data from the Health Survey for England to calculate the differences we ought to expect to have seen given the individual-level socioeconomic characteristics of the residents. The observed disparities between the two neighbourhoods were considerably greater than this null model predicted. There were also different patterns of smoking in proximity to children in the two neighbourhoods. Conclusions/Significance: The differences in observed smoking, drinking alcohol, and physical activity between these tw

Nature of b-1,3-Glucan-Exposing Features on Candida albicans Cell Wall and Their Modulation

Funding Information: This work was supported by a programme grant from the UK Medical Research Council (MR/M026663/1; MR/M026663/2) and by the Medical Research Council Centre for Medical Mycology (MR/N006364/1; MR/N006364/2). NARG acknowledges Wellcome support for a Senior Investigator (101873/Z/13/Z), Collaborative (200208/A/15/Z; 215599/Z/19/Z) and Strategic Awards (097377/Z11/Z). MGN was supported by an ERC Advanced Grant (833247) and a Spinoza Grant of the Netherlands Organization for Scientific Research.Peer reviewedPublisher PD

Helicobacter pylori versus the Host: Remodeling of the Bacterial Outer Membrane Is Required for Survival in the Gastric Mucosa

Modification of bacterial surface structures, such as the lipid A portion of lipopolysaccharide (LPS), is used by many pathogenic bacteria to help evade the host innate immune response. Helicobacter pylori, a gram-negative bacterium capable of chronic colonization of the human stomach, modifies its lipid A by removal of phosphate groups from the 1- and 4′-positions of the lipid A backbone. In this study, we identify the enzyme responsible for dephosphorylation of the lipid A 4′-phosphate group in H. pylori, Jhp1487 (LpxF). To ascertain the role these modifications play in the pathogenesis of H. pylori, we created mutants in lpxE (1-phosphatase), lpxF (4′-phosphatase) and a double lpxE/F mutant. Analysis of lipid A isolated from lpxE and lpxF mutants revealed lipid A species with a 1 or 4′-phosphate group, respectively while the double lpxE/F mutant revealed a bis-phosphorylated lipid A. Mutants lacking lpxE, lpxF, or lpxE/F show a 16, 360 and 1020 fold increase in sensitivity to the cationic antimicrobial peptide polymyxin B, respectively. Moreover, a similar loss of resistance is seen against a variety of CAMPs found in the human body including LL37, β-defensin 2, and P-113. Using a fluorescent derivative of polymyxin we demonstrate that, unlike wild type bacteria, polymyxin readily associates with the lpxE/F mutant. Presumably, the increase in the negative charge of H. pylori LPS allows for binding of the peptide to the bacterial surface. Interestingly, the action of LpxE and LpxF was shown to decrease recognition of Helicobacter LPS by the innate immune receptor, Toll-like Receptor 4. Furthermore, lpxE/F mutants were unable to colonize the gastric mucosa of C57BL/6J and C57BL/6J tlr4 -/- mice when compared to wild type H. pylori. Our results demonstrate that dephosphorylation of the lipid A domain of H. pylori LPS by LpxE and LpxF is key to its ability to colonize a mammalian host

Alterations of brain and cerebellar proteomes linked to Aβ and tau pathology in a female triple-transgenic murine model of Alzheimer's disease

The triple-transgenic Alzheimer (3 × Tg-AD) mouse expresses mutant PS1M146V, APPswe, and tauP301L transgenes and progressively develops plaques and neurofibrillary tangles with a temporal- and region-specific profile that resembles the neuropathological progression of Alzheimer's disease (AD). In this study, we used proteomic approaches such as two-dimensional gel electrophoresis and mass spectrometry to investigate the alterations in protein expression occurring in the brain and cerebellum of 3 × Tg-AD and presenilin-1 (PS1) knock-in mice (animals that do not develop Aβ- or tau-dependent pathology nor cognitive decline and were used as control). Finally, using the Ingenuity Pathway Analysis we evaluated novel networks and molecular pathways involved in this AD model. We identified several differentially expressed spots and analysis of 3 × Tg-AD brains showed a significant downregulation of synaptic proteins that are involved in neurotransmitter synthesis, storage and release, as well as a set of proteins that are associated with cytoskeleton assembly and energy metabolism. Interestingly, in the cerebellum, a structure not affected by AD, we found an upregulation of proteins involved in carbohydrate metabolism and protein catabolism. Our findings help to unravel the pathogenic brain mechanisms set in motion by mutant amyloid precursor protein (APP) and hyperphosphorylated tau. These data also reveal cerebellar pathways that may be important to counteract the pathogenic actions of Aβ and tau, and ultimately offer novel targets for therapeutic intervention