New and Exciting in PLoS ONE

There are 30 new articles in PLoS ONE published yesterday and another 23 today. As always, you should rate the articles, post notes and comments and send trackbacks when you blog about the papers. You can now also easily place articles on various social services (CiteULike, Mendeley, Connotea, Stumbleupon, Facebook and Digg) with just one click. Here are my own picks for the week - you go and look for your own favourites:

Systematic Differences in Impact across Publication Tracks at PNAS:

Citation data can be used to evaluate the editorial policies and procedures of scientific journals. Here we investigate citation counts for the three different publication tracks of the Proceedings of the National Academy of Sciences of the United States of America (PNAS). This analysis explores the consequences of differences in editor and referee selection, while controlling for the prestige of the journal in which the papers appear. We find that papers authored and "Contributed" by NAS members (Track III) are on average cited less often than papers that are "Communicated" for others by NAS members (Track I) or submitted directly via the standard peer review process (Track II). However, we also find that the variance in the citation count of Contributed papers, and to a lesser extent Communicated papers, is larger than for direct submissions. Therefore when examining the 10% most-cited papers from each track, Contributed papers receive the most citations, followed by Communicated papers, while Direct submissions receive the least citations. Our findings suggest that PNAS "Contributed" papers, in which NAS-member authors select their own reviewers, balance an overall lower impact with an increased probability of publishing exceptional papers. This analysis demonstrates that different editorial procedures are associated with different levels of impact, even within the same prominent journal, and raises interesting questions about the most appropriate metrics for judging an editorial policy's success.

Survey of the Quality of Experimental Design, Statistical Analysis and Reporting of Research Using Animals:

For scientific, ethical and economic reasons, experiments involving animals should be appropriately designed, correctly analysed and transparently reported. This increases the scientific validity of the results, and maximises the knowledge gained from each experiment. A minimum amount of relevant information must be included in scientific publications to ensure that the methods and results of a study can be reviewed, analysed and repeated. Omitting essential information can raise scientific and ethical concerns. We report the findings of a systematic survey of reporting, experimental design and statistical analysis in published biomedical research using laboratory animals. Medline and EMBASE were searched for studies reporting research on live rats, mice and non-human primates carried out in UK and US publicly funded research establishments. Detailed information was collected from 271 publications, about the objective or hypothesis of the study, the number, sex, age and/or weight of animals used, and experimental and statistical methods. Only 59% of the studies stated the hypothesis or objective of the study and the number and characteristics of the animals used. Appropriate and efficient experimental design is a critical component of high-quality science. Most of the papers surveyed did not use randomisation (87%) or blinding (86%), to reduce bias in animal selection and outcome assessment. Only 70% of the publications that used statistical methods described their methods and presented the results with a measure of error or variability. This survey has identified a number of issues that need to be addressed in order to improve experimental design and reporting in publications describing research using animals. Scientific publication is a powerful and important source of information; the authors of scientific publications therefore have a responsibility to describe their methods and results comprehensively, accurately and transparently, and peer reviewers and journal editors share the responsibility to ensure that published studies fulfil these criteria.

Why Some Women Look Young for Their Age:

The desire of many to look young for their age has led to the establishment of a large cosmetics industry. However, the features of appearance that primarily determine how old women look for their age and whether genetic or environmental factors predominately influence such features are largely unknown. We studied the facial appearance of 102 pairs of female Danish twins aged 59 to 81 as well as 162 British females aged 45 to 75. Skin wrinkling, hair graying and lip height were significantly and independently associated with how old the women looked for their age. The appearance of facial sun-damage was also found to be significantly correlated to how old women look for their age and was primarily due to its commonality with the appearance of skin wrinkles. There was also considerable variation in the perceived age data that was unaccounted for. Composite facial images created from women who looked young or old for their age indicated that the structure of subcutaneous tissue was partly responsible. Heritability analyses of the appearance features revealed that perceived age, pigmented age spots, skin wrinkles and the appearance of sun-damage were influenced more or less equally by genetic and environmental factors. Hair graying, recession of hair from the forehead and lip height were influenced mainly by genetic factors whereas environmental factors influenced hair thinning. These findings indicate that women who look young for their age have large lips, avoid sun-exposure and possess genetic factors that protect against the development of gray hair and skin wrinkles. The findings also demonstrate that perceived age is a better biomarker of skin, hair and facial aging than chronological age.

Maggot Secretions Skew Monocyte-Macrophage Differentiation Away from a Pro-Inflammatory to a Pro-Angiogenic Type:

Maggots of the blowfly Lucilia sericata are used for the treatment of chronic wounds. Earlier we reported maggot secretions to inhibit pro-inflammatory responses of human monocytes. The aim of this study was to investigate the effect of maggot secretions on the differentiation of monocytes into pro-inflammatory (MÃ-1) and anti-inflammatory/pro-angiogenic macrophages (MÃ-2) as these cells play a central role in wound healing. Freshly isolated monocytes were incubated with secretions and GM-CSF or M-CSF for 6 days and then stimulated with LPS or LTA for 18 h. The expression of cell surface molecules and the levels of cytokines, chemokines and growth factors in supernatants were measured. Our results showed secretions to affect monocyte-macrophage differentiation leading to MÃ-1 with a partial MÃ-2-like morphology but lacking CD163, which is characteristic for MÃ-2. In response to LPS or LTA, secretions-differentiated MÃ-1 produced less pro-inflammatory cytokines (TNF-α, IL-12p40 and MIF) than control cells. Similar results were observed for MÃ-2 when stimulated with low concentrations of LPS. Furthermore, secretions dose-dependently led to MÃ-1 and MÃ-2 characterized by an altered chemokine production. Secretions led to MÃ-2, but not MÃ-1, producing enhanced levels of the growth factors bFGF and VEGF, as compared to control cells. The expression of cell-surface receptors involved in LPS/LTA was enhanced by secretions, that of CD86 and HLA-DR down-regulated, while receptors involved in phagocytosis remained largely unaffected. Maggot secretions skew the differentiation of monocytes into macrophages away from a pro-inflammatory to a pro-angiogenic type.

Influenza Morbidity and Mortality in Elderly Patients Receiving Statins: A Cohort Study:

Statins possess immunomodulatory properties and have been proposed for reducing morbidity during an influenza pandemic. We sought to evaluate the effect of statins on hospitalizations and deaths related to seasonal influenza outbreaks. We conducted a population-based cohort study over 10 influenza seasons (1996 to 2006) using linked administrative databases in Ontario, Canada. We identified all adults older than 65 years who had received an influenza vaccination prior to the start of influenza season and distinguished those also prescribed statins (23%) from those not also prescribed statins (77%). Propensity-based matching, which accounted for each individual's likelihood of receiving a statin, yielded a final cohort of 2,240,638 patients, exactly half of whom received statins. Statins were associated with small protective effects against pneumonia hospitalization (odds ratio [OR] 0.92; 95% CI 0.89-0.95), 30-day pneumonia mortality (0.84; 95% CI 0.77-0.91), and all-cause mortality (0.87; 95% CI 0.84-0.89). These protective effects attenuated substantially after multivariate adjustment and when we excluded multiple observations for each individual, declined over time, differed across propensity score quintiles and risk groups, and were unchanged during post-influenza season periods. The main limitations of this study were the observational study design, the non-specific outcomes, and the lack of information on medications while hospitalized. Statin use is associated with a statistically significant but minimal protective effect against influenza morbidity that can easily be attributed to residual confounding. Public health officials and clinicians should focus on other measures to reduce morbidity and mortality from the next influenza pandemic.

Toward the Discovery of Vaccine Adjuvants: Coupling In Silico Screening and In Vitro Analysis of Antagonist Binding to Human and Mouse CCR4 Receptors:

Adjuvants enhance or modify an immune response that is made to an antigen. An antagonist of the chemokine CCR4 receptor can display adjuvant-like properties by diminishing the ability of CD4+CD25+ regulatory T cells (Tregs) to down-regulate immune responses. Here, we have used protein modelling to create a plausible chemokine receptor model with the aim of using virtual screening to identify potential small molecule chemokine antagonists. A combination of homology modelling and molecular docking was used to create a model of the CCR4 receptor in order to investigate potential lead compounds that display antagonistic properties. Three-dimensional structure-based virtual screening of the CCR4 receptor identified 116 small molecules that were calculated to have a high affinity for the receptor; these were tested experimentally for CCR4 antagonism. Fifteen of these small molecules were shown to inhibit specifically CCR4-mediated cell migration, including that of CCR4+ Tregs. Our CCR4 antagonists act as adjuvants augmenting human T cell proliferation in an in vitro immune response model and compound SP50 increases T cell and antibody responses in vivo when combined with vaccine antigens of Mycobacterium tuberculosis and Plasmodium yoelii in mice.